PMID- 12177099
TI  - Fulvestrant, formerly ICI 182,780, is as effective as anastrozole in
      postmenopausal women with advanced breast cancer progressing after prior
      endocrine treatment.
AB  - PURPOSE: To compare the efficacy and tolerability of fulvestrant (formerly ICI
      182,780) and anastrozole in postmenopausal women with advanced breast cancer
      progressing after prior endocrine treatment. PATIENTS AND METHODS: Patients (n =
      451) with advanced breast cancer were randomized to receive fulvestrant 250 mg as
      a once-monthly (one x 5 mL) intramuscular injection or an oral dose of
      anastrozole 1 mg in this open, parallel-group, multicenter trial. The primary end
      point was time to progression (TTP). Secondary end points included objective
      response (OR) rates, defined as complete response (CR) or partial response (PR),
      duration of response (DOR), and tolerability. RESULTS: Patients were followed for
      a median period of 14.4 months. In terms of TTP, fulvestrant was as effective as
      anastrozole (hazard ratio, 0.98; confidence interval [CI], 0.80 to 1.21; P =.84).
      Median TTP was 5.5 months for fulvestrant and 5.1 months for anastrozole. OR
      rates showed a numerical advantage for fulvestrant (20.7%) over anastrozole
      (15.7%) (odds ratio, 1.38; CI, 0.84 to 2.29; P =.20). Clinical benefit rates (CR
      + PR + stable disease > or = 24 weeks) were 44.6% for fulvestrant and 45.0% for
      anastrozole. Median DOR was 14.3 months for fulvestrant and 14.0 months for
      anastrozole. Both treatments were well tolerated, with 3.2% and 1.3% of
      fulvestrant- and anastrozole-treated patients, respectively, withdrawn from
      treatment because of an adverse event. CONCLUSION: Fulvestrant was as effective
      as anastrozole. These data confirm that fulvestrant is an additional, effective,
      and well-tolerated treatment for advanced breast cancer in postmenopausal women
      whose disease progressed on prior endocrine therapy.

PMID- 12177100
TI  - Molecular detection of cytokeratin-19-positive cells in the peripheral blood of
      patients with operable breast cancer: evaluation of their prognostic
      significance.
AB  - PURPOSE: To evaluate the prognostic significance of molecular detection of
      cytokeratin 19 (CK-19) mRNA-positive cells by nested reverse transcriptase
      polymerase chain reaction (RT-PCR) in the peripheral blood of women with stages I
      and II breast cancer before adjuvant chemotherapy. PATIENTS AND METHODS: The
      sensitivity and specificity of CK-19 mRNA detection by nested RT-PCR were
      investigated using MCF-7 and ARH-77 cells and blood from healthy women and
      patients with hematologic malignancies, metastatic colorectal cancer, and early
      and metastatic breast cancer. Peripheral blood from 148 patients with operable
      breast cancer, obtained before initiation of any adjuvant therapy, was tested for
      the presence of CK-19 mRNA-positive cells. RESULTS: The nested RT-PCR assay for
      CK-19 mRNA detected one MCF-7 tumor cell in 10(6) normal peripheral blood
      mononuclear cells in four of five experiments; no signal was detected with the CK
      19-negative ARH-77 cells. CK-19 mRNA was detected in the peripheral blood of 3.7%
      of healthy blood donors, 14.3% of patients with hematologic malignancies, and
      3.2% of patients with metastatic colorectal cancer. Detection rates for CK-19
      mRNA-positive cells in the bone marrow/blood of patients with early or metastatic
      breast cancer were 63%/30% and 74%/52%, respectively. For stages I and II breast
      cancer, detection of CK-19-positive cells in the peripheral blood before adjuvant
      therapy was associated with reduced disease-free interval (P =.0007) and overall
      survival (P =.01). In multivariate analysis, detection of peripheral-blood CK-19
      positive cells was an independent prognostic factor for disease relapse and
      death. CONCLUSION: Molecular detection of CK-19 mRNA-positive cells by RT-PCR in
      the peripheral blood of patients with stages I and II breast cancer before
      initiation of adjuvant therapy has independent prognostic value as a marker of
      poor clinical outcome.

PMID- 12177101
TI  - Effect of breast magnetic resonance imaging on the clinical management of women
      with early-stage breast carcinoma.
AB  - PURPOSE: To determine the impact of breast magnetic resonance imaging (MRI) on
      the clinical management of patients with early-stage breast cancer. PATIENTS AND
      METHODS: A review was performed of the records of 207 women with early-stage
      breast cancer (including five women with bilateral disease) who underwent breast
      MRI during work-up for breast conservation treatment. All patients presented with
      clinical stage 0, I, or II disease. For each patient, a determination was made
      whether the breast MRI affected the clinical management, and if so, whether the
      patient was well served by the change in management. RESULTS: The MRI findings
      affected the clinical management in 43 cases (20% of 212 breast cancers). Based
      on the pathology findings and the overall clinical course for each case, the
      breast MRI was judged to have had a strongly favorable effect on management in 18
      cases (8%), a somewhat favorable effect in six cases (3%), an uncertain effect in
      five cases (2%), a somewhat unfavorable effect in 11 cases (5%), and a strongly
      unfavorable effect in three cases (1%). The effect of MRI was not significantly
      different for invasive carcinoma compared with ductal carcinoma-in-situ (all P >
      or =.27). However, the effect of MRI was significantly greater when the MRI was
      performed before an excisional biopsy (P =.0011) or for larger tumors (P =.0089).
      CONCLUSIONS: Breast MRI alters the clinical management for a sizable fraction of
      women with early-stage breast cancer and appears to offer clinically useful
      information for determining optimal local treatment.

PMID- 12177102
TI  - Factorial design considerations.
AB  - PURPOSE: Factorial designs may be proposed to test extra questions within a
      clinical trial. A common approach to sample size and analysis for factorial
      trials assumes no statistical interactions and does not adjust for multiple
      testing. This investigation considered the trade-off between potential gains from
      testing more questions with fewer patients versus how often a factorial trial
      might arrive at an incorrect conclusion. METHODS: A simulation study of a 2 x 2
      design (observation v chemotherapy v radiation therapy v the combination) was
      performed under various conditions, including effect of one, both, or neither
      treatment and absence or presence of statistical interaction (effect of one
      treatment differed according to the presence of the other). Three analysis
      approaches were investigated, one assuming no interaction, a second testing first
      for interaction, and the third testing for interaction as well as adjusting for
      multiple testing. The approaches were compared with respect to the probability of
      selecting the correct treatment arm. RESULTS: No one approach was superior.
      Testing for interaction was beneficial in some settings but detrimental in
      others. Under some scenarios, the factorial design improved efficiency, but under
      others, all three approaches resulted in poor probability of selecting the
      correct treatment arm at the end of the trial. CONCLUSION: Extra efficiency is
      possible, but it is difficult to predict when favorable conditions exist. If a
      factorial design is used, potential efficiency gains should be weighed against
      potential loss of power to arrive at the correct conclusion under possible
      scenarios of interest.

PMID- 12177103
TI  - Preradiation chemotherapy in primary high-risk brainstem tumors: phase II study
      CCG-9941 of the Children's Cancer Group.
AB  - PURPOSE: This Children's Cancer Group group-wide phase II trial evaluated the
      efficacy and toxicity of two chemotherapy arms administered before
      hyperfractionated external-beam radiotherapy (HFEBRT). PATIENTS AND METHODS:
      Thirty-two patients with newly diagnosed brainstem gliomas were randomly assigned
      to regimen A and 31 to regimen B. Regimen A comprised three courses of
      carboplatin, etoposide, and vincristine; regimen B comprised cisplatin,
      etoposide, cyclophosphamide, and vincristine. Both arms included granulocyte
      colony-stimulating factor. Patients were evaluated by magnetic resonance imaging
      after induction chemotherapy and HFEBRT at a dose of 72 Gy. RESULTS: Ten percent
      +/- 5% of regimen A patients objectively responded to chemotherapy. For combined
      induction and radiotherapy, 27% +/- 9% of patients improved. The
      neuroradiographic response rate for regimen B was 19% +/- 8% for chemotherapy and
      23% +/- 9% after HFEBRT. Response rates were not statistically significant
      between regimens after induction or chemotherapy/HFEBRT. Event-free survival was
      17% +/- 5% (estimate +/- SE) at 1 year and 6% +/- 3% at 2 years. Survival was
      significantly longer among patients who responded to chemotherapy (P <.05). Among
      patients who received regimen A induction, grades 3 and 4 leukopenia were
      observed in 50% to 65%, with one toxicity-related death. For regimen B, severe
      leukopenia occurred in 86% to 100%, with febrile neutropenia in 48% to 60% per
      course. CONCLUSION: Neither chemotherapy regimen meaningfully improved response
      rate, event-free survival, or overall survival relative to previous series of
      patients with brainstem gliomas who received radiotherapy with or without
      chemotherapy.

PMID- 12177104
TI  - Treatment of unresectable and metastatic hepatoblastoma: a pediatric oncology
      group phase II study.
AB  - PURPOSE: To estimate the disease-response rate, proportion of patients whose
      tumors can be made resectable, event-free survival (EFS), and toxicity in
      children with unresectable or metastatic hepatoblastoma (HB) after sequential
      treatment with the following: (1) carboplatin (CARBO); (2) CARBO, vincristine,
      and fluorouracil (CARBO-VCR-5-FU); and (3) high-dose cisplatin and etoposide
      (HDDP-ETOP). PATIENTS AND METHODS: Thirty-three assessable patients with stage
      III (n = 22) and stage IV (n = 11) HB were treated sequentially with one course
      of CARBO (700 mg/m(2)), followed by three courses of CARBO (700 mg/m(2)), day 0;
      5-FU (1,000 mg/m(2)/d), by continuous infusion days 0 to 2; and VCR (1.5
      mg/m(2)), days 0, 7, and 14. After that therapy, patients whose tumors were
      resectable underwent surgery and then received two additional courses of CARBO
      VCR-5-FU. Children whose tumors remained unresectable after CARBO-VCR-5-FU or who
      demonstrated no response or progressive disease during this therapy received two
      courses of HDDP (40 mg/m(2)/d), days 1 to 5; and ETOP (100 mg/m(2)/d), days 2 to
      4. RESULTS: Five-year EFS estimates were 59% +/- 11% for stage III disease (n =
      22) and 27% +/- 16% for stage IV disease (n = 11), respectively (P =.037). Twenty
      seven (82%) of 33 patients had at least a partial response to chemotherapy; 18
      (55%) of 33 responded to CARBO; 24 (80%) of 30 responded to CARBO and CARBO-VCR-5
      FU; and nine (75%) of 12 responded to HDDP-ETOP. Surgical resection was achieved
      in 19 (58%) of 33 patients, including 15 (68%) of 22 stage III patients and four
      (36%) of 11 stage IV patients. Five-year EFS for patients whose tumors were
      completely resected was 79% +/- 10%. CONCLUSION: Patients treated sequentially
      with CARBO, CARBO-VCR-5-FU, and HDDP-ETOP had response rates and EFS comparable
      to other therapeutic regimens. This regimen is effective in treating localized,
      unresectable HB and potentially has less toxicity than other regimens. Novel
      approaches are needed for patients with metastatic disease.

PMID- 12177105
TI  - Lead-in phase to randomized trial of motexafin gadolinium and whole-brain
      radiation for patients with brain metastases: centralized assessment of magnetic
      resonance imaging, neurocognitive, and neurologic end points.
AB  - PURPOSE: Motexafin gadolinium is a redox mediator that selectively targets tumor
      cells, is detectable by magnetic resonance imaging (MRI), and enhances the effect
      of radiation therapy. This lead-in phase to a randomized trial served to evaluate
      radiologic, neurocognitive, and neurologic progression end points and to evaluate
      the safety and radiologic response of motexafin gadolinium administered
      concurrently with 30 Gy in 10-fraction whole-brain radiation therapy for the
      treatment of brain metastases. PATIENTS AND METHODS: Motexafin gadolinium (5.0
      mg/kg/d for 10 days) was administered before each radiation treatment in this
      prospective international trial. Patients were evaluated by MRI, neurologic
      examinations, and neurocognitive tests. Prospective criteria and centralized
      review procedures were established for radiologic, neurocognitive, and neurologic
      progression end points. RESULTS: Twenty-five patients with brain metastases from
      lung (52%) and breast (24%) cancer, recursive partitioning analysis class 2
      (96%), and an average of 11 brain metastases were enrolled. Neurocognitive
      function was highly impaired at presentation. Motexafin gadolinium was well
      tolerated. Freedom from neurologic progression was 77% at 1 year. Median survival
      was 5.0 months. In 29% of patients, the cause of death was brain metastasis
      progression. The radiologic response rate was 68%. Motexafin gadolinium's tumor
      selectivity was established with MRI. CONCLUSION: (1) Centralized neurologic
      progression scoring that incorporated neurocognitive tests was implemented
      successfully. (2) Motexafin gadolinium was well tolerated. (3) Local control,
      measured by radiologic response rate, neurologic progression, and death caused by
      progression of brain metastasis, seemed to be improved compared with historical
      results. A randomized phase III trial using these methods for evaluation of
      efficacy has just been completed.

PMID- 12177106
TI  - Concurrent cisplatin, etoposide, and chest radiotherapy in pathologic stage IIIB
      non-small-cell lung cancer: a Southwest Oncology Group phase II study, SWOG 9019.
AB  - PURPOSE: There are no published survival data after chemoradiotherapy (chemoRT)
      in pathologically documented stage IIIB non-small-cell lung cancer. Studies of
      radiotherapy (RT) alone or chemotherapy followed by RT yield 5-year survivals
      less than 10%. The Southwest Oncology Group (SWOG) employed the same concurrent
      chemoRT induction regimen used in its predecessor trimodality trial to determine
      the efficacy, safety, and long-term outcome of replacing postinduction surgery
      with additional chemoRT. PATIENTS AND METHODS: Eligible patients for SWOG-9019
      had pathologic documentation of T4N0/1, T4N2, or N3 stage IIIB non-small-cell
      lung cancer. They had pulmonary function adequate to withstand combined-modality
      therapy, identical to the requirements of the previous trial with postchemoRT
      surgery. Induction therapy was two cycles of cisplatin plus etoposide (PE)
      concurrent with once-daily thoracic RT (45 Gy). In the absence of progressive
      disease, RT was completed to 61 Gy, with two additional cycles of cisplatin plus
      etoposide. RESULTS: Fifty eligible patients were accrued with tumor-node (TN)
      substage confirmed on central review: 18, T4N0/1; 12, T4N2; and 20, N3. Grade 4
      neutropenia was the most common toxicity (32%). Grade 3/4 esophagitis occurred in
      12% and 8%. Median follow-up was 52 months, and overall median survival was 15
      months (10 to 22, 95% confidence interval). Three- and 5-year survivals were 17%
      and 15% (5-year T4N0/1, 17%; T4N2, 13%; and N3, 15%). CONCLUSION: Feasibility and
      long-term survival support the application of these results as a standard against
      which mature outcomes of chemoRT trials with new chemotherapy agents can be
      compared. These results also justify use of the SWOG-9019 approach as a control
      arm in ongoing phase III trials.

PMID- 12177107
TI  - Tobacco use outcomes among patients with lung cancer treated for nicotine
      dependence.
AB  - PURPOSE: There is a current lack of consensus about the effectiveness of nicotine
      dependence treatment for cancer patients. This retrospective study examined the 6
      month tobacco abstinence rate among lung cancer patients treated clinically for
      nicotine dependence. PATIENTS AND METHODS: A date-of-treatment matched case
      control design was used to compare lung cancer patients (201 lung cancer
      patients, 41% female) and nonlung cancer patients (201 controls, 45% female)
      treated in the Mayo Clinic Nicotine Dependence Center between 1988 and 2000. The
      intervention involves a brief consultation with a nicotine dependence counselor.
      A treatment plan individualized to the patient's needs is then developed. The
      primary end point was the self-reported, 7-day point prevalence abstinence from
      tobacco at 6-month follow-up. RESULTS: At baseline, compared with the controls,
      the lung cancer patients were significantly older (P <.001), reported higher
      motivation to stop smoking (P =.003), and were at a higher stage of change (P
      =.002). The 6-month tobacco abstinence rate was 22% for the lung cancer patients
      compared with 14% of the control patients (P =.024). After adjusting for age,
      sex, baseline cigarettes smoked per day, and stage of change, no significant
      difference was detected between lung cancer patients and controls on the tobacco
      abstinence rate. CONCLUSION: The results suggest that nicotine dependence
      treatment is effective for patients with a diagnosis of lung cancer. The majority
      of lung cancer patients were motivated to stop smoking.

PMID- 12177108
TI  - Effect of timing of pulmonary metastases identification on prognosis of patients
      with osteosarcoma: the Japanese Musculoskeletal Oncology Group study.
AB  - PURPOSE: The prognostic value of the time of identification of lung metastasis
      was investigated in 280 patients with metastatic lung osteosarcoma as a multi
      institutional study of the Japanese Musculoskeletal Oncology Group. PATIENTS AND
      METHODS: The 280 patients with lung metastasis were divided into four groups:
      group 1, patients with lung metastasis identified at initial presentation; group
      2, those with lung metastasis identified during preoperative chemotherapy; group
      3, those with lung metastasis identified during postoperative chemotherapy, and
      group 4, those with lung metastasis identified after completion of treatment.
      Survivals of the four groups were compared. Additionally, the effects of number
      of metastatic nodules, metastasectomy, and the effect of chemotherapy on the
      primary tumor on survival of the four groups were analyzed. RESULTS: There were
      46 patients in group 1, 30 in group 2, 94 in group 3, and 110 in group 4. The
      overall 2-year survival rates from the time of identification of lung metastasis
      were 33%, 31%, 24%, and 40% for groups 1, 2, 3, and 4, respectively, whereas the
      5-year survival rates were 18%, 0%, 6%, and 31%, respectively. Patients in group
      4 thus demonstrated significantly better prognosis than any of the other patients
      (P <.0001). CONCLUSION: Time of identification of lung metastasis is an important
      prognostic factor. In terms of clinical behavior, groups 2 and 3 are completely
      different than group 4. These data ensure the need to stratify stage III
      osteosarcomas into subgroups according to the time of diagnosis of lung
      metastases. To improve the survival of osteosarcoma patients, new treatment
      modalities should be introduced into the treatment armamentarium for lung
      metastasis from osteosarcoma, especially in groups 1, 2, and 3.

PMID- 12177109
TI  - Neuroprotective effect of reduced glutathione on oxaliplatin-based chemotherapy
      in advanced colorectal cancer: a randomized, double-blind, placebo-controlled
      trial.
AB  - PURPOSE: We performed a randomized, double-blind, placebo-controlled trial to
      assess the efficacy of glutathione (GSH) in the prevention of oxaliplatin-induced
      neurotoxicity. PATIENTS AND METHODS: Fifty-two patients treated with a bimonthly
      oxaliplatin-based regimen were randomized to receive GSH (1,500 mg/m(2) over a 15
      minute infusion period before oxaliplatin) or normal saline solution. Clinical
      neurologic evaluation and electrophysiologic investigations were performed at
      baseline and after four (oxaliplatin dose, 400 mg/m(2)), eight (oxaliplatin dose,
      800 mg/m(2)), and 12 (oxaliplatin dose, 1,200 mg/m(2)) cycles of treatment.
      RESULTS: At the fourth cycle, seven patients showed clinically evident neuropathy
      in the GSH arm, whereas 11 patients in the placebo arm did. After the eighth
      cycle, nine of 21 assessable patients in the GSH arm suffered from neurotoxicity
      compared with 15 of 19 in the placebo arm. With regard to grade 2 to 4 National
      Cancer Institute common toxicity criteria, 11 patients experienced neuropathy in
      the placebo arm compared with only two patients in the GSH arm (P =.003). After
      12 cycles, grade 2 to 4 neurotoxicity was observed in three patients in the GSH
      arm and in eight patients in the placebo arm (P =.004). The neurophysiologic
      investigations (sural sensory nerve conduction) showed a statistically
      significant reduction of the values in the placebo arm but not in the GSH arm.
      The response rate was 26.9% in the GSH arm and 23.1% in the placebo arm, showing
      no reduction in activity of oxaliplatin. CONCLUSION: This study provides evidence
      that GSH is a promising drug for the prevention of oxaliplatin-induced
      neuropathy, and that it does not reduce the clinical activity of oxaliplatin.

PMID- 12177110
TI  - Second malignant neoplasms among long-term survivors of Hodgkin's disease: a
      population-based evaluation over 25 years.
AB  - PURPOSE: To quantify the relative and absolute excess risks (AER) of site
      specific second cancers, in particular solid tumors, among long-term survivors of
      Hodgkin's disease (HD) and to assess risks according to age at HD diagnosis,
      attained age, and time since initial treatment. PATIENTS AND METHODS: Data from
      32,591 HD patients (1,111 25-year survivors) reported to 16 population-based
      cancer registries in North America and Europe (1935 to 1994) were analyzed.
      RESULTS: Two thousand one hundred fifty-three second cancers (observed-to
      expected ratio [O/E] = 2.3; 95% confidence interval [CI] = 2.2 to 2.4), including
      1,726 solid tumors (O/E = 2.0; 95% CI, 1.9 to 2.0) were reported. Cancers of the
      lung (observed [Obs] = 377; O/E = 2.9), digestive tract (Obs = 376; O/E = 1.7),
      and female breast (Obs = 234; O/E = 2.0) accounted for the largest number of
      subsequent malignancies. Twenty-five years after HD diagnosis, the actuarial risk
      of developing a solid tumor was 21.9%. The relative risk of solid neoplasms
      decreased with increasing age at HD diagnosis, however, patients aged 51 to 60
      years at HD diagnosis sustained the highest cancer burden (AER = 79.2/10,000
      patients/year). After a progressive rise in relative risk and AER of all solid
      tumors over time, there was an apparent downturn in risk at 25 years. Temporal
      trends and treatment group distribution for cancers of the esophagus, stomach,
      rectum, female breast, bladder, thyroid, and bone/connective tissue were
      suggestive of a radiogenic effect. CONCLUSION: Significantly increased risks of
      second cancers were observed in all HD age groups. Although significantly
      elevated risks of stomach, female breast, and uterine cervix cancers persisted
      for 25 years, an apparent decrease in relative risk and AER of solid tumors at
      other sites is suggested.

PMID- 12177111
TI  - Symptom experiences: perceptual accuracy between advanced-stage cancer patients
      and family caregivers in the home care setting.
AB  - PURPOSE: This study used a comparative descriptive design to compare family
      caregivers' and advanced-stage cancer patients' perceptions of patients'
      multidimensional symptom experiences on presence, frequency, severity, and
      distress. PATIENTS AND METHODS: A convenience sample of 98 dyads, composed of
      advanced-stage heterogeneous cancer patients and their caregivers, completed the
      Memorial Symptom Assessment Scale in the home care setting on a one-time basis.
      This scale is a 32-item Likert-type scale for assessing the presence, frequency,
      severity, and distress arising from symptoms in cancer patients. RESULTS: There
      was confirmation of trends previously described in related studies where, for
      example, caregivers tend to overreport on symptom experiences. However, the
      degree of absolute difference between patient and caregiver responses was
      normally around 1 unit (on a theoretical range of 0 to 4 units). Levels of
      patient-caregiver agreement were better on more concrete questions related to
      symptom frequency, severity, and distress than on broad questions related to the
      presence of a symptom. Patients and caregivers achieved better levels of
      agreement on physical versus psychological symptoms. CONCLUSION: The findings
      indicated that family caregivers can provide reasonable proxy or complementary
      reports on patient symptom experiences of frequency, severity, and distress.
      However, family caregivers have greater difficulty in achieving high levels of
      accuracy on psychological versus physical symptoms.

PMID- 12177112
TI  - Phase I and pharmacokinetic study of E7070, a novel chloroindolyl sulfonamide
      cell-cycle inhibitor, administered as a one-hour infusion every three weeks in
      patients with advanced cancer.
AB  - PURPOSE: The objectives were to determine the maximum-tolerated dose, the
      recommended dose, the dose-limiting toxicity, the pharmacokinetics, and the
      activity of E7070, a novel cell-cycle inhibitor. PATIENTS AND METHODS: E7070 was
      given as a 1-hour intravenous infusion every 3 weeks in two groups of patients
      with advanced solid tumors who met prespecified eligibility criteria (group A) or
      who met the same eligibility criteria but in addition were less heavily
      pretreated and had more favorable liver functions (group B). RESULTS: Forty
      patients (31 patients in group A and nine patients in group B) were entered. Dose
      escalation proceeded through eight levels (range, 50 to 1,000 mg/m(2)). In group
      A, neutropenia and thrombocytopenia were dose-limiting toxicities occurring
      during the first cycle in two of seven patients treated at the doses of 700
      mg/m(2) and two of four patients treated at 800 mg/m(2). Identical dose-limiting
      toxicities were observed in zero of six and two of three patients from group B at
      doses of 800 and 1,000 mg/m(2), respectively. Other toxicities included acne-like
      skin eruption, mucositis, conjunctivitis, nausea, fatigue, and alopecia. At doses
      greater than 400 mg/m(2), the area under the concentration-time curve increased
      disproportionately to the administered dose. Tumor stabilization lasting > or = 6
      months was observed in six assessable patients. CONCLUSION: The recommended doses
      of E7070 in this schedule were 700 mg/m(2) (group A) and 800 mg/m(2) in patients
      who were less heavily pretreated (group B) with a moderate tumor burden.
      Prolonged disease stabilization observed in this study might warrant further
      investigation of E7070 in selected tumor types.

PMID- 12177113
TI  - Initial clinical trial of oral TAC-101, a novel retinoic acid receptor-alpha
      selective retinoid, in patients with advanced cancer.
AB  - PURPOSE: The goals of this study were to determine the safety, toxicity, and
      pharmacokinetics of TAC-101, a novel synthetic retinoic acid receptor-alpha (RAR
      alpha) selective retinoid, in patients with advanced cancer. PATIENTS AND
      METHODS: Twenty-nine patients at two centers received oral TAC-101 at doses
      ranging from 12 to 34 mg/m(2)/d. Pharmacokinetic sampling was performed on days 1
      and 28. RESULTS: The most frequent toxicities were myalgia/arthralgia, fatigue,
      and triglyceridemia. No dose-limiting toxicities were observed within the first
      28 days up to 28 mg/m(2). However, seven of 21 patients experienced venous
      thromboembolic events (VTEs) during TAC-101 treatment. Eight additional patients
      who received 34 mg/m(2) were treated after a hypercoagulable work-up to exclude
      potential risk factors for VTE, and two of eight patients subsequently
      experienced VTEs. The maximum tolerated dose was exceeded at 34 mg/m(2)/d within
      the first 28 days, with one grade 3 hypertriglyceridemia, two grade 3
      myalgia/arthralgia, and one grade 3 fatigue. One patient with advanced non-small
      cell lung cancer had a complete response. No other responses were observed. No
      autoinduction of metabolism was observed with dosing over 28 days. CONCLUSION:
      This is the first human clinical study with TAC-101, a RAR-alpha selective
      retinoid. Musculoskeletal toxicity and hypertriglyceridemia were observed
      characteristics of previously studied retinoids. The recommended phase II dose is
      24 mg/m(2) with this treatment schedule. Alternative treatment schedules and
      prospective evaluation of thrombotic risk will be investigated in subsequent
      studies.

PMID- 12177114
TI  - Phase I clinical and pharmacokinetic study of pemetrexed and carboplatin in
      patients with malignant pleural mesothelioma.
AB  - PURPOSE: To determine the maximum tolerated dose (MTD) of pemetrexed and
      carboplatin given in combination, to derive a recommended dose for phase II
      studies, and to explore its efficacy. We assessed toxicities and explored the
      activity of the drug combination exclusively in patients with malignant pleural
      mesothelioma (MPM). The pharmacokinetics of both agents was investigated.
      PATIENTS AND METHODS: Twenty-seven patients (23 male, four female) with MPM were
      treated on five escalating dose levels. Doses ranged from pemetrexed 400 mg/m(2)
      (as a 10-minute intravenous infusion), followed by carboplatin area under the
      plasma concentration-time curve (AUC) 4 mg/mL.min (as a 30-minute intravenous
      infusion) to pemetrexed 500 mg/m(2), carboplatin AUC 6 mg/mL.min. All patients
      had a World Health Organization performance status of 1. A total of 163 courses
      of treatment were administered (median, six; range, one to 10). RESULTS: The main
      toxicity was hematologic, particularly neutropenia, although this was
      characteristically short-lived and caused few clinical problems. The MTD was
      pemetrexed 500 mg/m(2), carboplatin AUC 6, because three of the five patients
      treated at this dose level experienced a dose-limiting toxicity. Eight partial
      responses (in 25 assessable patients) were observed for a response rate of 32%.
      Seventy percent of patients noticed an improvement in symptoms, usually (84%)
      after only two courses. Median time to progression was 305 days, and median
      survival time was 451 days. CONCLUSION: The MTD was pemetrexed 500 mg/m(2) and
      carboplatin AUC 6 mg/mL.min. The recommended phase II dose of the combination is
      pemetrexed 500 mg/m(2) and carboplatin AUC 5 mg/mL.min. The combination is both
      active and well tolerated in MPM and deserves further exploration.

PMID- 12177115
TI  - Radiolabeled anti-CD20 monoclonal antibodies for the treatment of B-cell
      lymphoma.

PMID- 12177116
TI  - Interleukin-2 and histamine dihydrochloride in metastatic melanoma.

PMID- 12177117
TI  - Carboplatin and topotecan combination and myelosuppression.

PMID- 12177118
TI  - Radiotherapy of carcinoma-in-situ of the testis.

PMID- 12177119
TI  - Cisplatin and dacarbazine with or without subcutaneous interleukin-2 and
      interferon alfa-2b in advanced melanoma outpatients.

PMID- 12177120
TI  - Acute oxaliplatin-induced peripheral-nerve hyperexcitability.

PMID- 12177121
TI  - Manipulating PEPC levels in plants.
AB  - This review examines the current understanding of the structural, functional and
      regulatory properties of C4 and C3 forms of higher plant phosphoenolpyruvate
      carboxylase. The emphasis is on the interactive metabolic and post-translational
      controls acting on the enzyme in the physiological context of C4 photosynthesis
      and the anaplerotic pathway. A brief overview is given concerning the recent
      developments of PEPC-based genetic engineering of C3 plants with the aim of
      improving photosynthetic performance in normal and limiting environmental
      conditions. So far, in spite of achieving a considerable increase in PEPC levels,
      more work needs to be done with respect to the correct dosage and location before
      that goal is reached. Some unpublished results on the transformation of maize
      with a sorghum C4 PEPC cDNA are also presented. They show that it is possible to
      increase photosynthetic PEPC levels in this C4 plant and that the modification in
      enzyme content has a pleiotropic physiological impact and, notably, an improved
      water use efficiency when water is limited.

PMID- 12177122
TI  - Stimulation of glycolysis in anaerobic elongation of pondweed (Potamogeton
      distinctus) turions.
AB  - Stem segments prepared from pondweed (Potamo geton distinctus A. Benn.) turions
      (overwintering buds) elongate in anaerobic conditions, whereas there is almost no
      elongation in air. The anaerobic elongation was accompanied by a decrease in dry
      weights of stem segments, mainly due to consumption of storage starch in the
      amyloplasts of stem cells. On the other hand, total contents of amino acids
      increased in stem segments, in which contents of alanine, valine, leucine, and
      isoleucine increased, but contents of asparatic acid decreased. Moreover,
      contents of lactate in stem tissues increased at an early stage of anaerobic
      incubation. In tracer experiments with 14C-glucose, 14C incorporation into stem
      tissues in anoxia was only half of that in normoxia. However, conversion of 14C
      to ethanol occurred exclusively in anoxia. 14C-labelled metabolites were analysed
      by two-dimensional cellulose thin-layer chromatography. 14C incorporation into
      sucrose and alanine was significantly increased in anoxia. The activity of
      alanine aminotransferase was enhanced by anoxia, suggesting that pyruvate is a
      precursor of alanine synthesis. The results suggest that pondweed turions produce
      energy necessary for anaerobic elongation by activating conversion of storage
      starch in the amyloplasts to ethanol, alanine and lactate.

PMID- 12177123
TI  - Bleaching herbicide effects on plastids of dark-grown plants: lipid composition
      of etioplasts in amitrole and norflurazon-treated barley leaves.
AB  - The effects of the bleaching herbicides amitrole (125 micro M) and norflurazon
      (100 micro M) on etioplast lipids were studied in barley plants (Hordeum vulgare
      L. cv. Express) grown for 7 d either at 20 degrees C or 30 degrees C in darkness.
      Total lipid, glycolipid and phospholipid contents of control etioplasts were
      increased at 30 degrees C in comparison with those at 20 degrees C. The two
      herbicides caused a decrease in the total lipid, glycolipid and phospholipid
      amounts compared to the untreated etioplasts and lowered the lipid to protein
      ratio. In the controls, monogalactosyldiacylglycerol (MGDG) and
      digalactosyldiacylglycerol (DGDG) accounted for about 66 mol% of the etioplast
      polar lipids, while the remainder was represented by
      sulphoquinovosyldiacylglycerol (SQDG) and phosphatidylglycerol (PG), in
      approximately equal proportions. Both amitrole and norflurazon increased MGDG at
      both temperatures, but decreased DGDG except with norflurazon at 30 degrees C. As
      a consequence, the MGDG to DGDG molar ratio was higher in the herbicide-treated
      etioplasts compared to the controls at both the growth temperatures. The amount
      of the negatively charged polar lipids SQDG and PG were decreased by treatments
      with amitrole at 20 degrees C and norflurazon at 30 degrees C. The two herbicides
      determined different responses in the fatty acid unsaturation of the individual
      polar lipids. Changes in the lipid composition of etioplasts and the interaction
      between the pigment-protein complex, protochlorophyllide-NADPH
      protochlorophyllide oxidoreductase, and polar lipids are discussed.

PMID- 12177124
TI  - Combined expression of S-VSPalpha in two different organelles enhances its
      accumulation and total lysine production in leaves of transgenic tobacco plants.
AB  - Soybean vegetative storage proteins (S-VSPs) accumulate to high levels in
      vacuoles of both wild types and heterologous plants. Here it is shown that
      directing S-VSPalpha to two different organelles-chloroplasts and vacuoles-in a
      single transgenic plant significantly increased its accumulation. Accumulation of
      S-VSPalpha in heterologous plants correlated with total soluble lysine. Using
      this approach with essential amino-acid-rich transgene proteins may lead to a
      breakthrough in improving plant nutritional quality.

PMID- 12177125
TI  - Differential Top10 promoter regulation by six tetracycline analogues in plant
      cells.
AB  - The effects of five tetracycline analogues, anhydrotetracycline, doxycycline,
      minocycline, oxytetracycline, and tetracycline, on Top10 promoter activity in NT1
      tobacco tissue culture cells have been analysed. The concentration that repressed
      Top10 promoter activity, the level of transgene repression and the kinetics of
      transgene de-repression were determined for each analogue, and could not be
      predicted from in vitro binding affinity to the tetracycline repressor or from
      comparison with animal cells. Doxycycline had the most potent effect on the Top10
      promoter and completely inhibited transgene expression at 4 nmol l(-1).
      Tetracycline was the most versatile of the analogues tested; tetracycline
      inhibited the Top10 promoter at 10 nmol l(-1) and was easily washed out to
      restore Top10-driven expression in 12-24 h. A study was also made of the
      suitability for plant research of a novel tetracycline analogue, GR33076X. In
      animal cells, GR33076X de-repressed Top10 promoter activity in the presence of
      inhibitory concentrations of anhydrotetracycline. In NT1, it is shown that GR
      33076X can antagonize repression of the Top10 promoter in the presence of
      tetracycline, but not of anhydrotetracycline or of doxycycline. Different
      tetracycline analogues can therefore be used to regulate the Top10 promoter in
      plant cells and this property may be exploited in planning an optimum course of
      transgene regulation.

PMID- 12177126
TI  - Characterization of berberine transport into Coptis japonica cells and the
      involvement of ABC protein.
AB  - Cultured Coptis japonica cells are able to take up berberine, a
      benzylisoquinoline alkaloid, from the medium and transport it exclusively into
      the vacuoles. Uptake activity depends on the growth phase of the cultured cells
      whereas the culture medium had no effect on uptake. Treatment with several
      inhibitors suggested that berberine uptake depended on the ATP level. Some
      inhibitors of P-glycoprotein, an ABC transporter involved in multiple drug
      resistance in cancer cells, strongly inhibited berberine uptake, whereas a
      specific inhibitor for glutathione biosynthesis and vacuolar ATPase, bafilomycin
      A1, had little effect. Vanadate-induced ATP trap experiments to detect ABC
      proteins expressed in C. japonica cells showed that three membrane proteins of
      between 120 and 150 kDa were photolabelled with 8-azido-[alpha-32P] ATP. Two
      revealed the same photoaffinity-labelling pattern as P-glycoprotein, and the
      interaction of these proteins with berberine was also demonstrated. These results
      suggest that ABC proteins of the MDR-type are involved in the uptake of berberine
      from the medium.

PMID- 12177127
TI  - In vitro freezing in microtitre plates applied to tobacco plants transformed with
      the inaZ gene of Pseudomonas syringae.
AB  - High throughput assays have been developed to measure the ice nucleation activity
      of transgenic tobacco, Nicotiana tabacum L. cv. Petit Havana SR1 plants
      expressing the ice nucleation gene, inaZ, from Pseudomonas syringae at a young
      seedling stage, as well as in leaf tissue. Both assays are carried out in 96-well
      microtitre plates. The first assay involves direct seeding in vitro, one seed per
      microtitre plate well containing Murashige-Skoog agar. When seedlings reach the
      two-leaf stage, they are exposed to freezing temperatures by floating the plates
      on a circulating alcohol bath set at temperatures colder than -9 degrees C. The
      second assay involves placing small leaf discs individually in microtitre plate
      wells containing sterile distilled water. The assays complement each other, give
      highly reproducible results, are technically simple and enable the detection of
      freezing events in large numbers of plants. The utility and limitations of these
      assays are discussed.

PMID- 12177128
TI  - Isolation and characterization of the CYP71D16 trichome-specific promoter from
      Nicotiana tabacum L.
AB  - Trichomes are specialized epidermal cells that produce secretions that are
      thought to provide a first line of defence against pests and pathogens. Many
      trichome-secreted compounds are used commercially as flavourings, medicines, etc.
      Described here is the cloning and characterization of the promoter of a tobacco
      trichome-specific P450 gene, CYP71D16. This promoter is shown to direct the
      specific expression of the reporter gene, beta-glucuronidase (GUS), in glandular
      trichomes of Nicotiana tabacum cv. T.I. 1068 at all developmental stages. With
      the full promoter, GUS activity was predominantly in the gland cell, with less in
      the stalk cell adjacent to the gland, and in lower stalk cells. GUS staining was
      also observed in the most distal trichome stalk cells of non-glandular trichomes
      found on variety T.I. 1112. Promoter deletion analysis revealed that the region
      from -223 to +111 bp is sufficient to direct trichome-specific expression, but
      not strong gland expression. Examination of the literature suggests that this is
      the first characterized trichome-specific-promoter shown to function at all
      stages of plant development. This promoter may provide efficient bioengineering
      to enhance pest and pathogen resistance, and for molecular farming based on the
      trichome gland system.

PMID- 12177129
TI  - Isolation and characterization of the orchid cytokinin oxidase DSCKX1 promoter.
AB  - The orchid DSCKX1 is a new member of the cytokinin oxidase gene family, which
      catalyses the degradation of cytokinins bearing unsaturated isoprenoid side
      chains. A 3.7 kb fragment upstream of the DSCKX1 coding region was isolated,
      sequenced and characterized by deletion analysis of DSCKX1::beta-glucuronidase
      gene fusions using transient orchid and stable Arabidopsis transformation
      systems. Functional analysis of 5' deletions defined the 5'-upstream region that
      directs the expression in distinct tissues. Regulatory elements affecting the
      cytokinin induction of the DSCKX1 gene have also been delineated

PMID- 12177130
TI  - Independent induction of two blue light-dependent monovalent anion transport
      systems in the plasma membrane of Monoraphidium braunii.
AB  - In the plasma membrane of the green alga Monoraphidium braunii there are at least
      two monovalent anion transport systems. One of them is specific for bicarbonate.
      This transport system is activated by blue light and its induction is triggered
      by a decrease in the external CO2 concentration. The second transport system is
      responsible for nitrate uptake at least. This transport system is also activated
      by blue light and its induction occurs when there is no ammonium in the external
      medium. Both transport systems are synthesized independently. Hence, when M.
      braunii cells grow with nitrate as the only nitrogen source under high CO2, they
      have a nitrate transport system but lack a bicarbonate transporter. Conversely,
      cells grown with ammonium under low CO2, have a bicarbonate transport system but
      lack a nitrate transporter. Both transport systems are induced in cells
      irradiated with white light in the absence of a carbon source, suggesting that
      there may be precursors in the plasma membrane that only need the synthesis and
      assembly of some component(s) to become fully active. The induction of nitrate
      and nitrite reductases, however, only takes place when a carbon source is
      supplied to the cells.

PMID- 12177131
TI  - Source-sink partitioning. Do we need Munch?
AB  - The simulation of phloem translocation by the Munch theory commonly uses
      resistances from sources to sinks: the resistances are therefore regarded as
      important in partitioning. Although resistance is generally a set constant, it is
      in fact strongly affected by viscosity, and thus the concentration of the
      transported solute. In this paper, the model of partitioning proposed by Minchin
      et al. was first corrected for variations in viscosity. The model was further
      modified, with the source considered as an activity of solute production rather
      than as a compartment concentration. When so defined, the source cannot differ
      from the sum of sink activities, largely outdating the source- or sink-limitation
      concepts. The corrected model confined the effect of resistances on the
      partitioning to low source activities. In the example of wheat grain filling
      analysed, such activities would be so low that they would correspond only to
      pathological conditions. In that case, the use of resistances in modelling is
      therefore just a mathematical burden, not even easily quantifiable since they are
      related to anatomical traits that are difficult to access. Leaving out
      resistances, it becomes easy to calculate the sink activities directly from the
      source activities, using an intuitive, accessible parametrization. The conditions
      for such a simplification are discussed.

PMID- 12177132
TI  - The major Nod factor of Bradyrhizobium japonicum promotes early growth of soybean
      and corn.
AB  - Greenhouse experiments were conducted to evaluate the effect of Nod factor Nod Bj
      V (C18:1, MeFuc) of Badyrhizobium japonicum on the growth of soybean and corn.
      Three-day-old seedlings of soybean and corn were grown in hydroponic solutions
      containing four concentrations (0, 10(-7), 10(-9) or 10(-11) M) of Nod factor.
      After 7 d of treatment, Nod factor enhanced soybean and corn biomass. Nod factor
      elicited profound effects on root growth resulting in 34-44% longer roots in
      soybean. More detailed analyses of the roots, using a scanner based image
      analysis system, revealed that Nod factor increased the total length, projected
      area and surface area of the roots and decreased the diameter of soybean roots,
      while it increased the total length of corn roots. Stem injection of soybean
      plants with 10(-7) M Nod factor resulted in increased dry matter accumulation.
      These results suggest that Nod factor, besides mediating early stages of
      nodulation, has more general plant growth-promoting effects.

PMID- 12177133
TI  - Decoupling of light intensity effects on the growth and development of C3 and C4
      weed species through sucrose supplementation.
AB  - Light availability has a profound effect on plant growth and development. One of
      the ways to study the effects of light intensity on plant growth and development
      without the confounding problem of photosynthate availability is sucrose
      injection/supplementation. A greenhouse experiment was conducted to evaluate the
      effects of light levels (0% and 75% shade) and sucrose injection (distilled water
      or 150 g sucrose l(-1)) on three weed species: redroot pigweed (Amaranthus
      retroflexus L., C4), lambsquarters (Chenopodium album L., C3) and velvetleaf
      (Abutilon theophrasti Medic., C3). The average total sucrose uptake was 7.6 and
      5.9 g per plant for 0% and 75% shading, respectively, representing 47% of the
      average total weed dry weight. Plants injected with sucrose had greater dry
      weights and shoot-to-root ratios under both light levels. In spite of sucrose
      supplementation the reduction in dry matter due to shading was greater for roots
      and reproductive structures than vegetative shoot tissues, indicating light level
      regulation of morphological changes resulting in changed C allocation that are
      independent of photosynthate availability. Dry weights of plants injected with
      sucrose under 75% shading were not different from distilled water-injected
      unshaded plants. However, both sucrose-injected and control plants, regardless of
      their photosynthetic pathways, underwent similar changes in allocation of dry
      matter and morphology due to shading, suggesting that these effects are strictly
      due to light intensity and not related to photosynthate availability.

PMID- 12177134
TI  - Morphological pattern of development affects the contribution of nitrogen
      reserves to regrowth of defoliated white clover (Trifolium repens L.).
AB  - The contribution of nitrogen reserves to regrowth following defoliation was
      studied in white clover plants (Trifolium repens cv. Huia). This was found to be
      closely linked to the morphological pattern of development of the aerial parts
      during the same period. Low temperature (6 degrees C) and short day exposure (8 h
      photoperiod) were used to induce dwarf development, i.e. to increase branching
      rate and to enhance new sites of leaf production during a period of regrowth.
      Treated plants exhibited a large reduction in leaf area and a large increase in
      leaf pool size for the first 10 d of a subsequent regrowth under standard culture
      conditions (16 h daylight; 22/18 degrees C day/night). The contribution of
      nitrogen from storage compounds in organs remaining after defoliation (sources)
      to regrowing tissues (sinks) was assessed by 15N pulse-chase labelling during
      regrowth following shoot removal. The mobilization of nitrogen reserves from
      storage tissues of regrowing clover was closely linked to the pattern of
      differentiation of the newly developed organs. It appeared that regrowth was
      supported less by endogenous N for the first 10 d after defoliation in treated
      plants, compared with control plants grown continuously in standard conditions.
      It is assumed that dwarf plants exhibit a lower dependence upon the mobilization
      of soluble proteins previously accumulated in roots and uncut stolons. The
      relationship between leaf development rate and N-uptake recovery following
      defoliation is discussed.

PMID- 12177135
TI  - Developing fruit direct post-floral morphogenesis in Helleborus niger L.
AB  - In fertilized flowers of Helleborus niger L., the sepals (the showy elements of
      the perianth at anthesis) grow, spread, and turn green, and the peduncles
      elongate. These processes did not proceed to completion when the pistils were
      removed at the bud stage, but could be restored by the application of plant
      growth regulators. Cytokinins and gibberellins stimulated the formation of well
      developed chloroplasts in, and spreading of, the sepals; the gibberellin, GA3,
      and the auxin, 4-chloroindole-3-acetic acid, promoted peduncle elongation. In
      fruit-bearing flowers, on the other hand, paclobutrazol, an inhibitor of
      gibberellin biosynthesis, reduced chlorophyll formation in the sepals, reversed
      sepal spreading, and inhibited peduncle elongation. Of the endogenous growth
      regulators in developing fruit, the following cytokinins were identified: zeatin,
      dihydrozeatin, N6-(2-isopentenyl)adenine and their ribosides and 9-glucosides.
      Zeatin riboside drastically increased in abundance (about 200 times), shortly
      after fertilization, when chlorophyll accumulation in the sepals occurred at the
      fastest rate, and remained the most prominent identified cytokinin until seed
      ripening.

PMID- 12177136
TI  - Aluminium-induced growth inhibition is associated with impaired efflux and influx
      of H+ across the plasma membrane in root apices of squash (Cucurbita pepo).
AB  - It is generally understood that the inhibition of growth of root apices is the
      initial effect caused by aluminium (Al) toxicity. The correlation between
      impaired H+-fluxes across the plasma membrane (PM) and Al-induced growth
      inhibition, Al accumulation and callose formation in root apices of squash
      (Cucurbita pepo L. cv. Tetsukabuto) is reported here. The root inhibition was
      dependent on Al concentration, and the duration of exposure, with the damage
      occurring preferentially in regions with high Al accumulation and callose
      formation. Using the fluorescent Al indicator (Morin), Al was localized in the
      cell walls of the root-tip cells after 3 h and in the whole root-tip cells after
      6 h of the Al treatment (50 micro M). The inhibition of H+-pumping rate in the
      highly purified PM vesicles obtained from the Al-treated apical root portions (1
      cm) coincided with the inhibition of root growth under Al stress. Furthermore, H+
      ATPase activity of PM vesicles prepared from the control root apices was strongly
      inhibited by Al in vitro in a dose-dependent manner. Approximately 50% inhibition
      was observed when PM vesicles were preincubated at Al concentration as low as 10
      micro M followed by the enzyme assay in the medium without Al. Using the pH
      indicator (bromocresol purple), it is shown that surface pH of the control (0 Al)
      root apices was strongly alkalized from the starting pH of 4.5 in a time
      dependent manner. By contrast, the surface pH changed only slightly in the Al
      treated root apices. The changes in surface pH mediated by altered dynamics of H+
      efflux and influx across the root tip PM play an important role in root growth as
      affected by Al.

PMID- 12177137
TI  - Identification of quantitative trait loci for cold-tolerance of photosynthesis in
      maize (Zea mays L.).
AB  - The effects of low growth temperature (15 degrees C) on the photosynthetic
      apparatus of maize were investigated in a set of 233 recombinant inbred lines by
      means of chlorophyll fluorescence, gas exchange measurements and analysis of
      photosynthetic pigments. A quantitative trait loci (QTL) analysis of five traits
      related to the functioning of the photosynthetic apparatus revealed a total of
      eight genomic regions that were significantly involved in the expression of the
      target traits. Four of these QTLs, located on chromosomes 1 (around 146 cM), 2
      (around 138 cM), 3 (around 70 cM), and 9 (around 62 cM), were identified across
      several traits and the phenotypic correlation observed among those traits
      confirmed at the genetic level. The two QTLs on chromosomes 1 and 9 were also
      expressed in leaves developed at near-optimal temperature (25 degrees C) whilst
      the two QTLs on chromosomes 2 and 3 were specific to leaves developed at sub
      optimal temperature. A QTL analysis conducted on traits related to the pigment
      composition of the leaves developed at 15 degrees C detected the QTL on
      chromosome 3 around 70 cM in 7 of the 11 traits analysed. This QTL accounted for
      up to 28% of the phenotypic variance of the quantum yield of electron transport
      at PSII in the fourth leaf after about 3 weeks at a sub-optimal temperature. The
      results presented here suggest that key gene(s) involved in the development of
      functional chloroplasts of maize at low temperature should be located on
      chromosome 3, close to the centromere.

PMID- 12177138
TI  - Effects of low chronic doses of ionizing radiation on antioxidant enzymes and
      G6PDH activities in Stipa capillata (Poaceae).
AB  - Stipa capillata (Poaceae) seeds were harvested from a control area (displaying a
      gamma dose rate of 0.23 micro Sv h(-1)) (C plants) and from two contaminated
      areas (5.4 and 25 micro Sv h(-1)) on the Semipalatinsk nuclear test site (SNTS)
      in Kazakhstan. The plants were grown for 124 d in a greenhouse under controlled
      conditions and exposed to three different treatments: (0) control; (E) external
      gamma irradiation delivered by a sealed 137Cs source with a dose rate of 66 micro
      Sv h(-1); (E+I) E treatment combined with internal beta irradiation due to
      contamination by 134Cs and 85Sr via root uptake from the soil. The root uptake
      led to a contamination of 100 Bq g(-1) for 85Sr and 5 Bq g(-1) for 134Cs (of
      plant dry weight) as measured at harvest. The activity of SOD, APX, GR, POD, CAT,
      G6PDH, and MDHAR enzymes was measured in leaves. Under (0) treatment, all enzymes
      showed similar activities, except POD, which had higher activity in plants
      originating from contaminated areas. Treatment (E) induced an enhancement of POD,
      CAT, GR, SOD, and G6PDH activities in plants originating from contaminated areas.
      Only control plants showed any stimulation of APX activity. Treatment (E+I) had
      no significant effect on APX, GR, CAT, and POD activities, but MDHAR activity was
      significantly reduced while SOD and G6PDH activities were significantly
      increased. The increase occurred in plants from all origins for SOD, with a
      greater magnitude as a function of their origin, and it occurred only in plants
      from the more contaminated populations for G6PDH. This suggests that exposure to
      a low dose rate of ionizing radiation for almost a half century in the original
      environment of Stipa has led to natural selection of the most adapted genotypes
      characterized by an efficient induction of anti-oxidant enzyme activities,
      especially SOD and G6PDH, involved in plant protection against reactive oxygen
      species.

PMID- 12177139
TI  - Expression analysis in plant and cell suspensions of CrCKR1, a cDNA encoding a
      histidine kinase receptor homologue in Catharanthus roseus (L.) G. Don.
AB  - A full length cDNA (CrCKR1) encoding a hybrid histidine kinase was isolated from
      a Catharanthus roseus cDNA library. The kinase belongs to the subfamily of
      cytokinin receptors represented by CRE1/AHK4/WOL in Arabidopsis thaliana. In cell
      suspensions, the expression of CrCKR1 is not affected by various stress and
      hormonal treatments but is stimulated in cells continuously exposed to cytokinin.
      In plants, CrCKR1 is strongly expressed only in the petals of mature flowers.
      These data suggest that CrCKR1 could take part in the mechanisms leading to the
      production of secondary metabolites in C. roseus.

PMID- 12177140
TI  - The novel rice (Oryza sativa L.) gene OsSbf1 encodes a putative member of the
      Na+/bile acid symporter family.
AB  - PCR-based differential screening was used to identify ethylene-induced genes in
      deep-water rice (Oryza sativa L.). One of the isolated cDNAs represented a novel
      protein, OsSBF1, with high homology to mammalian Na+/bile acid transporters and
      to sodium-dependent transporters from bacteria. One highly homologous protein and
      three less conserved homologues were identified in Arabidopsis thaliana
      indicating that Sbf proteins exist in monocot and dicot plant species. Expression
      of OsSbf1 in deep-water rice was shown to be elevated by growth-inducing
      treatments. Since bile acids have not been found in plants to date a possible
      function of SBF proteins may be in the transport of structurally related
      sulphonated brassinosteroids.

PMID- 12177141
TI  - Olfactory sensitivity to changes in environmental [Ca(2+)] in the freshwater
      teleost Carassius auratus: an olfactory role for the Ca(2+)-sensing receptor?
AB  - Olfactory sensitivity to changes in environmental Ca(2+) has been demonstrated in
      two teleost species; a salmonid (Oncorhynchus nerka) and a marine/estuarine
      perciform (Sparus aurata). To assess whether this phenomenon is restricted to
      species that normally experience large fluctuations in external ion
      concentrations (e.g. moving from sea water to fresh water) or is present in a
      much wider range of species, we investigated olfactory Ca(2+) sensitivity in the
      goldfish (Carassius auratus), which is a stenohaline, non-migratory freshwater
      cyprinid. Extracellular recording from the olfactory bulb in vivo by
      electroencephalogram (EEG) demonstrated that the olfactory system is acutely
      sensitive to changes in external Ca(2+) within the range that this species is
      likely to encounter in the wild (0.05-3 mmol l(-1)). The olfactory system
      responded to increases in external calcium with increasing bulbar activity in a
      manner that fitted a conventional Hill plot with an apparent EC(50) of 0.9+/-0.3
      mmol l(-1) (close to both ambient and plasma free [Ca(2+)]) and an apparent Hill
      coefficient of 1.1+/-0.3 (means +/- S.E.M., N=6). Thresholds of detection were
      below 50 micro mol l(-1). Some olfactory sensitivity to changes in external
      [Na(+)] was also recorded, but with a much higher threshold of detection (3.7
      mmol l(-1)). The olfactory system of goldfish was much less sensitive to changes
      in [Mg(2+)] and [K(+)]. Preliminary data suggest that Ca(2+) and Mg(2+) are
      detected by the same mechanism, although with a much higher affinity for Ca(2+).
      Olfactory sensitivity to Na(+) may warn freshwater fish that they are reaching
      the limit of their osmotic tolerance when in an estuarine environment. Olfaction
      of serine, a potent odorant in fish, was not dependent on the presence of
      external Ca(2+) or Na(+). Finally, the teleost Ca(2+)-sensing receptor (Ca-SR)
      was shown to be highly expressed in a subpopulation of olfactory receptor
      neurones by both immunocytochemistry and in situ hybridisation. The olfactory
      sensitivity to Ca(2+) (and Mg(2+)) is therefore likely to be mediated by the Ca
      SR. We suggest that olfactory Ca(2+) sensitivity is a widespread phenomenon in
      teleosts and may have an input into the physiological mechanisms regulating
      internal calcium homeostasis.

PMID- 12177142
TI  - Active ammonia excretion across the gills of the green shore crab Carcinus
      maenas: participation of Na(+)/K(+)-ATPase, V-type H(+)-ATPase and functional
      microtubules.
AB  - Although aquatic animals are generally believed to export nitrogenous waste by
      diffusion of NH(3) or NH(4)(+) across external epithelia, evidence for active
      ammonia excretion has been found in a number of species. In the euryhaline green
      shore crab Carcinus maenas, active excretion of ammonia across isolated gills is
      reduced by inhibitors of the Na(+)/K(+)-ATPase and vacuolar-type H(+)-ATPase. In
      addition, a functional dynamic microtubule network is necessary, since
      application of colchicine, taxol or thiabendazole leads to almost complete
      blockage of active and gradient-driven ammonia excretion. Actin filaments seem
      not to play a role in the excretory process. The NH(4)(+)-dependent short-circuit
      current and the conductance of the isolated cuticle were reduced in a dose
      dependent manner by amiloride, a non-specific inhibitor of the Na(+)/H(+)
      exchanger and Na(+) channels. Combined with an analysis of gill morphology, the
      strong intracellular but weak apical abundance of V-type H(+)-ATPase and the fact
      that ammonia flux rates are equal under buffered and unbuffered experimental
      conditions, our observations suggest a hypothetical model of transepithelial
      ammonia movement that features active uptake across the basolateral membrane,
      sequestration in acidified vesicles, vesicle transport via microtubules and
      exocytosis at the apical membrane.

PMID- 12177143
TI  - Incubation temperature modulates post-hatching thermoregulatory behavior in the
      Madagascar ground gecko, Paroedura pictus.
AB  - All vertebrates regulate body temperature within narrow limits, regardless of
      their physiological capabilities. When do these limits develop, and can they be
      modified by manipulations of the developmental thermal environment? We addressed
      these questions by incubating the eggs of the Madagascar ground gecko, Paroedura
      pictus, at three temperatures and by assessing thermoregulatory behavior in
      hatchlings. Thermoregulatory behavior was assessed using a two-choice shuttle
      paradigm, and skin temperatures were measured non-invasively using infrared
      thermography. The shuttling behavior of hatchlings was systematically affected by
      the temperature at which they were incubated, and follow-up tests suggested that
      this effect persisted for at least three weeks post-hatching. The body
      temperature data from the shuttling experiment were used to model
      thermoregulatory behavior in a complex thermal environment; the model predicted
      systematic effects of incubation temperature on thermal preference. The
      specificity of the alteration in thermoregulatory behavior by incubation
      temperature is compelling and provides evidence for powerful pre-hatching
      influences on a fundamental, life-sustaining behavioral process.

PMID- 12177144
TI  - Collision-avoidance and landing responses are mediated by separate pathways in
      the fruit fly, Drosophila melanogaster.
AB  - Flies rely heavily on visual feedback for several aspects of flight control. As a
      fly approaches an object, the image projected across its retina expands,
      providing the fly with visual feedback that can be used either to trigger a
      collision-avoidance maneuver or a landing response. To determine how a fly makes
      the decision to land on or avoid a looming object, we measured the behaviors
      generated in response to an expanding image during tethered flight in a visual
      closed-loop flight arena. During these experiments, each fly varied its wing
      stroke kinematics to actively control the azimuth position of a 15 degrees x 15
      degrees square within its visual field. Periodically, the square symmetrically
      expanded in both the horizontal and vertical directions. We measured changes in
      the fly's wing-stroke amplitude and frequency in response to the expanding square
      while optically tracking the position of its legs to monitor stereotyped landing
      responses. Although this stimulus could elicit both the landing responses and
      collision-avoidance reactions, separate pathways appear to mediate the two
      behaviors. For example, if the square is in the lateral portion of the fly's
      field of view at the onset of expansion, the fly increases stroke amplitude in
      one wing while decreasing amplitude in the other, indicative of a collision
      avoidance maneuver. In contrast, frontal expansion elicits an increase in wing
      beat frequency and leg extension, indicative of a landing response. To further
      characterize the sensitivity of these responses to expansion rate, we tested a
      range of expansion velocities from 100 to 10 000 degrees s(-1). Differences in
      the latency of both the collision-avoidance reactions and the landing responses
      with expansion rate supported the hypothesis that the two behaviors are mediated
      by separate pathways. To examine the effects of visual feedback on the magnitude
      and time course of the two behaviors, we presented the stimulus under open-loop
      conditions, such that the fly's response did not alter the position of the
      expanding square. From our results we suggest a model that takes into account the
      spatial sensitivities and temporal latencies of the collision-avoidance and
      landing responses, and is sufficient to schematically represent how the fly uses
      integration of motion information in deciding whether to turn or land when
      confronted with an expanding object.

PMID- 12177145
TI  - Mechanism allowing an insect to survive complete dehydration and extreme
      temperatures.
AB  - Cryptobiosis describes the state of an organism whose body water is completely
      dehydrated and metabolic activity has become undetectable. Our study aimed to
      elucidate the physiological mechanism of cryptobiosis in the highest cryptobiotic
      invertebrate, Polypedilum vanderplanki. Larvae of this insect rapidly accumulated
      a large amount of the carbohydrate, trehalose, (18% of dry body mass) during
      desiccation for 2 days, suggesting that a high level of trehalose accumulation
      contributed to the successful induction of cryptobiosis in P. vanderplanki as
      well as in other lower cryptobiotic organisms. When larvae deprived of the brain,
      suboesophageal ganglion (SG) and thoracic ganglia (TG) were completely dehydrated
      and then rehydrated, they were able to recover and move actively. During
      desiccation, such larvae also accumulated trehalose, although only about half as
      much as the intact larvae. It is concluded that the brain, SG and TG do not
      affect the induction and termination of cryptobiosis, and hence in this higher
      multicellular animal cryptobiosis is independent of brain, SG and TG regulation,
      just as in plants or in unicellular organisms.

PMID- 12177146
TI  - Dynamic stabilization of rapid hexapedal locomotion.
AB  - To stabilize locomotion, animals must generate forces appropriate to overcome the
      effects of perturbations and to maintain a desired speed or direction of
      movement. We studied the stabilizing mechanism employed by rapidly running
      insects by using a novel apparatus to perturb running cockroaches (Blaberus
      discoidalis). The apparatus used chemical propellants to accelerate a small
      projectile, generating reaction force impulses of less than 10 ms duration. The
      apparatus was mounted onto the thorax of the insect, oriented to propel the
      projectile laterally and loaded with propellant sufficient to cause a nearly
      tenfold increase in lateral velocity relative to maxima observed during
      unperturbed locomotion. Cockroaches were able to recover from these perturbations
      in 27+/-12 ms (mean +/- S.D., N=9) when running on a high-friction substratum.
      Lateral velocity began to decrease 13+/-5 ms (mean +/- S.D., N=11) following the
      start of a perturbation, a time comparable with the fastest reflexes measured in
      cockroaches. Cockroaches did not require step transitions to recover from lateral
      perturbations. Instead, they exhibited viscoelastic behavior in the lateral
      direction, with spring constants similar to those observed during unperturbed
      locomotion. The rapid onset of recovery from lateral perturbations supports the
      possibility that, during fast locomotion, intrinsic properties of the
      musculoskeletal system augment neural stabilization by reflexes.

PMID- 12177147
TI  - The locust frontal ganglion: a central pattern generator network controlling
      foregut rhythmic motor patterns.
AB  - The frontal ganglion (FG) is part of the insect stomatogastric nervous system and
      is found in most insect orders. Previous work has shown that in the desert
      locust, Schistocerca gregaria, the FG constitutes a major source of innervation
      to the foregut. In an in vitro preparation, isolated from all descending and
      sensory inputs, the FG spontaneously generated rhythmic multi-unit bursts of
      action potentials that could be recorded from all its efferent nerves. The
      consistent endogenous FG rhythmic pattern indicates the presence of a central
      pattern generator network. We found the appearance of in vitro rhythmic activity
      to be strongly correlated with the physiological state of the donor locust. A
      robust pattern emerged only after a period of saline superfusion, if the locust
      had a very full foregut and crop, or if the animal was close to ecdysis.
      Accordingly, haemolymph collected at these stages inhibited an ongoing rhythmic
      pattern when applied onto the ganglion. We present this novel central pattern
      generating system as a basis for future work on the neural network
      characterisation and its role in generating and controlling behaviour.

PMID- 12177148
TI  - The role of the frontal ganglion in locust feeding and moulting related
      behaviours.
AB  - In the desert locust, Schistocerca gregaria, the frontal ganglion (FG) plays a
      key role in control of foregut movements, and constitutes a source of innervation
      to the foregut dilator muscles. In this work we studied the generation and
      characteristics of FG motor outputs in two distinct and fundamental behaviours:
      feeding and moulting. The FG motor pattern was found to be complex, and strongly
      dependent on the locust's physiological and behavioural state. Rhythmic activity
      of the foregut was dependent on the amount of food present in the crop; animals
      with food in their crop demonstrated higher FG burst frequency than those with
      empty crop. A very full gut inhibited the FG rhythm altogether. When no feeding
      related foregut pattern was observed, the FG motor output was strongly correlated
      with the locust's ventilation pattern. This ventilation-related rhythm was
      dominant in pre-moulting locusts. During the moult, synchronization with the
      ventilation pattern can be transiently switched off, revealing the endogenous
      (feeding-related) FG pattern. This presumably happens during vigorous air
      swallowing, and could also be induced experimentally. Our findings suggest that
      the FG central pattern generator can be modulated to generate a variety of motor
      outputs under different physiological conditions and behavioural contexts.

PMID- 12177149
TI  - Exploring the sialome of the tick Ixodes scapularis.
AB  - To attempt description of the set of mRNA and protein (sialome) expressed in the
      salivary glands of the tick Ixodes scapularis, we randomly sequenced 735 clones
      of a full-length salivary gland cDNA library of this arthropod and performed
      Edman degradation of protein bands from salivary gland homogenates (SGH) and
      saliva separated by SDS-PAGE. The sequences were grouped into 410 clusters, of
      which 383 are not associated with known I. scapularis sequences. 15- and 17
      protein bands from PAGE yielded amino-terminal information on the saliva and
      salivary gland gels, respectively. We attributed 19 of these sequences to
      translation products of the cDNA library. Full-length sequences were obtained for
      87 clones. Among these protein sequences are several protease inhibitors of
      distinct classes, metalloproteases, novel proteins with histamine-binding
      domains, and several peptide families of unknown function displaying different
      conserved cysteine residues, many of which contain single Kunitz domains. This
      work provides information into the diversity of messages expressed in the
      salivary glands of I. scapularis, describes novel sequences that may be
      responsible for known biological activites, indicates further biological
      activities that may be present in I. scapularis saliva and identifies novel
      vaccine targets that may be used in Lyme disease prevention.

PMID- 12177150
TI  - Intensity control during target approach in echolocating bats; stereotypical
      sensori-motor behaviour in Daubenton's bats, Myotis daubentonii.
AB  - When approaching a prey target, bats have been found to decrease the intensity of
      their emitted echolocation pulses, called intensity compensation. In this paper
      we examine whether intensity compensation in the echolocation of bats is flexible
      or stereotyped. We recorded the echolocation calls of Daubenton's bats (Myotis
      daubentonii) while the animals attacked targets of different dimensions. Myotis
      daubentonii reduced the peak sound pressure level emitted by about 4dB for each
      halving of distance, irrespective of the target presented (mealworms and two
      different sizes of spheres). The absolute sound pressure level emitted by the bat
      is not or only a little affected by target strength. Furthermore, the decrease in
      emitted intensity over distance shows less scatter than the same intensity over
      time for the last 20 cm of target approach. The bats matched the emitted
      intensity to target distance equally well for the spheres (aspect-invariant
      target strength) as for the mealworms (aspect-dependent echo strength). We
      therefore conclude that intensity compensation does not rely on feedback
      information from received intensity, but instead follows a stereotyped pattern.

PMID- 12177151
TI  - Swimming in needlefish (Belonidae): anguilliform locomotion with fins.
AB  - The Atlantic needlefish (Strongylura marina) is a unique anguilliform swimmer in
      that it possesses prominent fins, lives in coastal surface-waters, and can propel
      itself across the surface of the water to escape predators. In a laboratory flow
      tank, steadily swimming needlefish perform a speed-dependent suite of behaviors
      while maintaining at least a half wavelength of undulation on the body at all
      times. To investigate the effects of discrete fins on anguilliform swimming, I
      used high-speed video to record body and fin kinematics at swimming speeds
      ranging from 0.25 to 2.0 L s(-1) (where L is the total body length). Analysis of
      axial kinematics indicates that needlefish are less efficient anguilliform
      swimmers than eels, indicated by their lower slip values. Body amplitudes
      increase with swimming speed, but unlike most fishes, tail-beat amplitude
      increases linearly and does not plateau at maximal swimming speeds. At 2.0 L s(
      1), the propulsive wave shortens and decelerates as it travels posteriorly, owing
      to the prominence of the median fins in the caudal region of the body. Analyses
      of fin kinematics show that at 1.0 L s(-1) the dorsal and anal fins are slightly
      less than 180 degrees out of phase with the body and approximately 225 degrees
      out of phase with the caudal fin. Needlefish exhibit two gait transitions using
      their pectoral fins. At 0.25 L s(-1), the pectoral fins oscillate but do not
      produce thrust, at 1.0 L s(-1) they are held abducted from the body, forming a
      positive dihedral that may reduce rolling moments, and above 2.0 L s(-1) they
      remain completely adducted.

PMID- 12177152
TI  - Carbon dioxide and pH affect sperm motility of white sturgeon (Acipenser
      transmontanus).
AB  - Maintenance of sperm at pH values less than approximately 7.5 inhibited the onset
      of motility when sperm were subsequently diluted with water; maintenance at pH
      values above approximately 8.2 was associated with maximal motility upon dilution
      with water. Within 5 approximately min of exposure to low pH buffer (pH 6.9),
      there was a 50% decline in sperm motility upon dilution with water suggesting
      that exposure to low pH interferes with motility within a time frame that may
      affect fertilization. In most instances, maintenance of sperm under CO(2) at a
      pressure of 4-5 kPa almost completely blocked their capacity for motility.
      Furthermore, exposing semen to increasing partial pressures of CO(2) up to about
      1 kPa resulted in a marked decrease in semen pH. These observations are
      consistent with the findings that the buffering capacity of semen is particularly
      low at physiological pH, and that this low buffering capacity corresponds to the
      highest pH sensitivity of the capacity for sperm motility. The low seminal
      buffering capacity may represent a physiological adaptation in the control of
      sperm function. It may also represent a vulnerability to environmental
      hypercapnia or metabolic acidosis.

PMID- 12177153
TI  - Post-prandial blood flow to the gastrointestinal tract is not compromised during
      hypoxia in the sea bass Dicentrarchus labrax.
AB  - The hypothesis that the increase in post-prandial splanchnic blood flow will be
      reduced during hypoxia to prioritise blood flow to other organs was tested by
      measuring cardiac output and gut blood flow during a stepwise hypoxic challenge
      (five steps, from 20.6 to 3.9 kPa, 5 min of exposure to each level) before and
      after feeding (equivalent to 2.9% of body mass). Splanchnic blood flow, both
      absolute and relative to cardiac output, increased after feeding. Mean post
      prandial gut blood flow increased by 71% (from 9.6+/-1.6 to 14.9+/-1.6 ml min(-1)
      kg(-1), means +/- S.E.M.). Before feeding, gut blood flow was 24.0% of cardiac
      output, and this increased significantly 24 h after feeding to 34.0%. The
      absolute post-prandial increase in gut blood flow (5.3+/-0.9 ml min(-1) kg(-1))
      was paralleled by an increase in cardiac output (5.4+/-2.1 ml min(-1) kg(-1)).
      Hypoxia decreased gut blood flow significantly from 9.6+/-1.6 to 3.7+/-1.1 ml
      min(-1) kg(-1), corresponding to a decrease in relative gut blood flow from 24 %
      to 13%. Contrary to our initial hypothesis, and although post-prandial absolute
      blood flow decreases during hypoxia, the relative proportion of cardiac output
      reaching the gut did not decrease (34.6% pre-hypoxia versus 26.7% during
      hypoxia), unlike the situation in non-feeding fish. We propose that, following
      feeding, relative gut blood flow is maintained because splanchnic hyperaemia
      occurs as a result of the release of local factors; consequently the reflex
      vasoconstriction of the gastrointestinal vasculature during hypoxia is not as
      effective in decreasing gut blood flow as it was before feeding because local
      hyperaemia out-competes the reflex regulation.

PMID- 12177154
TI  - Differential scaling of locomotor performance in small and large terrestrial
      mammals.
AB  - It has been observed that the relationship between locomotor performance and body
      mass in terrestrial mammals does not follow a single linear trend when the entire
      range of body mass is considered. Large taxa tend to show different scaling
      exponents compared to those of small taxa, suggesting that there would be a
      differential scaling between small and large mammals. This pattern, noted
      previously for several morphological traits in mammals, has been explained to
      occur as a result of mechanical constraints over bones due to the differential
      effect of gravity on small and large-sized forms. The relationship between
      maximum relative running speed (body length s(-1)) and body mass was analysed in
      142 species of terrestrial mammals, in order to evaluate whether the relative
      locomotor performance shows a differential scaling depending on the range of mass
      analysed, and whether the scaling pattern is consistent with the idea of
      mechanical constraints on locomotor performance. The scaling of relative
      locomotor performance proved to be non-linear when the entire range of body
      masses was considered and showed a differential scaling between small and large
      mammals. Among the small species, a negative, although nearly independent,
      relationship with body mass was noted. In contrast, maximum relative running
      speed in large mammals showed a strong negative relationship with body mass. This
      reduction in locomotor performance was correlated with a decrease in the ability
      to withstand the forces applied on bones and may be understood as a necessary
      stress reduction mechanism for assuring the structural integrity of the limb
      skeleton in large species.

PMID- 12177155
TI  - Energy metabolism of male and female tarantulas (Aphonopelma anax) during
      locomotion.
AB  - We examined aerobic performance traits in male and female tarantulas (Aphonopelma
      anax). Reproductive fitness in these males relies heavily on locomotory searching
      to locate receptive females, which are fossorial and sedentary. Because of this
      dimorphism in life history, we predicted that selection in males would enhance
      their ability to sustain high levels of aerobic metabolism (compared with
      females) to support increased locomotory activity during the mating season. Rates
      of carbon dioxide production were measured in an enclosed variable-speed
      treadmill. Steady-state rates of carbon dioxide production increased linearly
      within the range of sustainable aerobic speeds for both males and females.
      Although there was substantial variation in physiological performance traits
      among individuals, there were no detectable intersexual differences in maximal
      rates of carbon dioxide production, maximal aerobic speed, minimum transport or
      factorial scope.

PMID- 12177156
TI  - Altitudinal variation in parental energy expenditure by white-crowned sparrows.
AB  - We used the doubly labeled water technique to measure daily energy expenditure
      (DEE) during the incubation and feeding nestling stages in two populations of
      white-crowned sparrows (Zonotrichia leucophrys) - one montane and migratory, the
      other coastal and sedentary - that differ in thermal environment and clutch size.
      We assessed the birds' thermal environment by continuously monitoring (among
      other variables) operative temperature and wind speed both in the open and within
      bushes and willow thickets occupied by sparrows. From these measurements, we
      derived several estimates of the birds' thermal environment, including standard
      operative temperature (T(es)). Shade air temperature and T(es) averaged 6.6 and
      10.3 degrees C lower, respectively, at the montane study site during DEE
      measurements. The montane population's DEE averaged 24% higher than that of the
      sea-level population (103.6+/-12.2 versus 83.7+/-9.6 kJ day(-1); means +/- S.D.,
      N=31 and 22, respectively), reflecting both its larger brood size (3.7 versus
      2.9) and the colder environment. The DEE:BMR ratio was lowest in the sea-level
      population (2.1 versus 2.6), but neither population worked to their physiological
      capacity to produce young. DEE was significantly correlated with temperature
      across populations, with T(es) explaining 42% of the variation in DEE.
      Statistically removing the effect of temperature by adjusting DEE to a common
      temperature reduced the difference in DEE between populations by 34% to 87.7 and
      100.8 kJ day(-1), respectively, for sea-level and montane populations. Basal and
      resting metabolic rates were similar in both populations, implying that greater
      activity in the montane population accounted for its higher temperature-adjusted
      DEE. Our results indicate that the thermal context within which behavior occurs
      can significantly affect interindividual variation in DEE. Attempts to assess
      reproductive effort by measuring DEE should therefore account explicitly for the
      effect of temperature.

PMID- 12177157
TI  - Respiration and energetics of embryonic development in a large altricial bird,
      the Australian pelican (Pelecanus conspicillatus).
AB  - We examined whether the previously reported low cost of embryonic development in
      pelicans could be attributed to a more efficient conversion of egg energy to
      hatchling tissues as a result of high initial egg water content, low embryonic
      metabolic rate and growth later in incubation than in more precocious species. We
      therefore determined egg and hatchling composition and the development of
      embryonic respiration in the Australian pelican Pelecanus conspicillatus, which
      lays one of the largest eggs (140-210 g) with an altricial developmental mode.
      The small yolk fraction (21%) is typical of all pelecaniforms; however, we found
      that intraspecific variability in fresh egg mass was related to water content
      (principally in the albumen), but independent of yolk mass (mean 13 g dry mass).
      P. conspicillatus eggs have, on average, 635 kJ of energy, irrespective of egg
      mass across the whole range of egg mass. The embryonic developmental pattern of
      O(2) consumption and CO(2) production showed clear plateaus lasting 2-3 days
      immediately prior to internal pipping, resembling the typical precocial pattern.
      However, the rate of pre-internal pipping O(2) consumption was low in comparison
      with that of precocial species of similar egg mass. There is no evidence to
      support the hypothesis that the observed plateau in rates of O(2) uptake is due
      to a diffusion limitation of the eggshell gas conductance in this species.
      Embryonic metabolic rate nearly doubled during the pipping period, but the mass
      independent metabolic rate of the hatchling was low in comparison with that of
      the resting adult. The total O(2) consumed (11 063 ml) is equivalent to 217.3 kJ
      (or 34% of egg energy) based on indirect calorimetry and the observed respiratory
      exchange ratio of 0.71. Thus, the cost of development (direct calorimetry) was
      0.29 kJ J(-1) in the egg (mean egg mass 168 g), which is one of lowest reported
      values. As a result, the production efficiency of pelican embryonic development
      was 61.6%, higher than the average for birds in general (56.9%) and, in
      particular, of seabirds that have prolonged incubation periods on the basis of
      egg mass. High efficiency in embryonic development in this species was attained
      as a result of rapid embryonic growth later in incubation, low hatchling energy
      density (23.6 kJ g(-1) dry matter) and dry matter content, low embryonic
      metabolic rate throughout incubation and a shorter than expected incubation
      period of 33 days (predicted 36 days).

PMID- 12177158
TI  - Hearing asymmetry and auditory acuity in the Australian bushcricket Requena
      verticalis (Listroscelidinae; Tettigoniidae; Orthoptera).
AB  - Fluctuating asymmetry in bilaterally placed sensory structures of insects may be
      considered maladaptive; natural selection should favour a symmetrical system.
      Among bushcrickets or katydids, threshold hearing sensitivity is, in part,
      dependent on the size of the auditory spiracle in the prothorax. We tested the
      degree of natural asymmetry in the hearing system of the ensiferan orthopteran
      Requena verticalis by measuring the size of the auditory spiracle of females.
      Naturally occurring asymmetry approached 8%, which translates to a hearing bias
      at a threshold of only 0.8 dB. Auditory asymmetry of females was experimentally
      exaggerated by packing cotton wool into either the right or left auditory
      spiracle. We made neurophysiological recordings from the ascending auditory T
      fibre in the neck connective and found that the left-right bias created by this
      operation approximated 5 dB; this is greater than that found in nature. For these
      experiments, sound was delivered to the operated side of the insect from a
      speaker placed at either 90 degrees or 30 degrees to the long-body axis. To test
      the influence of this induced auditory bias, free-moving females were allowed to
      orient towards a speaker emitting male calls at near-natural call intensities of
      51 and 82 dB (SPL), 80 cm from the speaker on a flat arena. There was no
      variation in angle or vector between experimental and control insects, and there
      was no difference in acuity between intensity. We discuss the relevance of
      threshold measurements of bushcricket hearing systems in regard to sound
      localisation and, from these experiments question any role of asymmetry.

PMID- 12177159
TI  - Mechanisms of acid secretion in pseudobranch cells of rainbow trout (Oncorhynchus
      mykiss).
AB  - Cell suspensions of rainbow trout Oncorhynchus mykiss pseudobranch, prepared by
      Ca(2+) depletion and mechanical maceration, contained a distinct population of
      cells that always kept their relatively cuboidal shape and did not round up in
      suspension or proliferate after adhering to the surface of cell culture dishes.
      Phasecontrast microscopy revealed an extensive system of basal membrane
      invaginations, and Na(+)-K(+)-ATPase- and anionexchanger-like immunoreactivity
      could be localized in cell membranes. The cells were characterized by a high
      mitochondrial density. Using specific antibodies, V-ATPase subunit B was
      localized in the plasma membrane. Using a cytosensor microphysiometer, the rate
      of acid secretion of these cells was measured and compared with the activity of a
      gill cell preparation. Incubation of pseudobranch cells with bafilomycin A1 (10(
      6) mol l(-1)), a specific inhibitor of V-ATPase, reduced the rate of acid
      secretion by about 10% under control conditions, while no effect of bafilomycin
      on the rate of acid secretion of gill cells was observed. Application of
      amiloride (5 x 10(-5) mol l(-1)) reduced the rate of acid secretion in cells of
      both organs, pseudobranch and gills. Incubation of pseudobranch cells with DIDS
      (10(-3) mol l(-1)) resulted in a minor increase in the rate of proton secretion,
      but in cells prepared from the gills of rainbow trout acid secretion was reduced
      by about 30-40%. It is concluded that pseudobranch cells are equipped with
      various pathways to secrete protons, and that the anion exchange activity
      especially of pseudobranch cells appears to be different from that in gills.

PMID- 12177160
TI  - Hepatic lipase: structure/function relationship, synthesis, and regulation.
AB  - Hepatic lipase (HL) is a lipolytic enzyme, synthesized by hepatocytes and found
      localized at the surface of liver sinusoid capillaries. In humans, the enzyme is
      mostly bound onto heparan-sulfate proteoglycans at the surface of hepatocytes and
      also of sinusoid endothelial cells. HL shares a number of functional domains with
      lipoprotein lipase and with other members of the lipase gene family. It is a
      secreted glycoprotein, and remodelling of the N-linked oligosaccharides appears
      to be crucial for the secretion process, rather than for the acquisition of the
      catalytic activity. HL is also present in adrenals and ovaries, where it might
      promote delivery of lipoprotein cholesterol for steroidogenesis. However,
      evidence of a local synthesis is still controversial. HL activity is fairly
      regulated according to the cell cholesterol content and to the hormonal status.
      Coordinate regulations have been reported for both HL and the scavenger-receptor
      B-I, suggesting complementary roles in cholesterol metabolism. However, genetic
      variants largely contribute to HL variability and their possible impact in the
      development of a dyslipidemic phenotype, or in a context of insulin-resistance,
      is discussed.

PMID- 12177161
TI  - Effects of sirolimus on plasma lipids, lipoprotein levels, and fatty acid
      metabolism in renal transplant patients.
AB  - Sirolimus (Rapammune, rapamycin, RAPA) is a potent immunosuppressive drug that
      reduces renal transplant rejection. Hyperlipidemia is a significant side effect
      of sirolimus treatment, and frequently leads to cardiovascular disease. This
      study was undertaken to determine the repeatability, reversibility, and dose
      dependence of the plasma lipid and apolipoprotein altering effects of sirolimus,
      and to elucidate the mechanism by which sirolimus induces hypertriglyceridemia in
      some renal transplant patients. Six patients with renal allografts maintained on
      cyclosporine A and prednisone were selected on the basis of their previous
      hyperlipidemic response to short term (14 days) sirolimus administration. For
      longer-term treatment, each patient was started on 10 mg/day sirolimus and
      continued as tolerated for 42 days to reinduce hyperlipidemia. Timed blood
      samples were analyzed for lipid, apolipoprotein, and sirolimus levels. During
      sirolimus administration, mean total plasma cholesterol increased from 214 mg/dl
      to 322 mg/dl (+50%; range 25-92%); LDL-cholesterol levels followed a similar
      pattern. Mean triglyceride level rose from 227 to 432 mg/dl (+95%; range 9-254%).
      ApoB-100 concentration rose from 124 to 160 mg/dl (+28%; P < 0.05). ApoC-III
      level increased from 28.9 to 55.5 mg/dl, +92%; (P < 0.013). These lipid and
      apolipoprotein changes were found to be repeatable, reversible, and dose
      dependent. [(13)C(4)]palmitate metabolic studies in four patients with
      hypertriglyceridemia indicated that the free fatty acid pool was expanded by
      sirolimus treatment (mean = 42.3%). Incorporation of [(13)C(4)]palmitate into
      triglycerides of VLDL, IDL, and LDL was decreased 38.3%, 42,1%, and 38.4%,
      respectively, by sirolimus treatment of these patients. These results suggest
      that sirolimus alters the insulin signaling pathway so as to increase adipose
      tissue lipase activity and/or decrease lipoprotein lipase activity, resulting in
      increased hepatic synthesis of triglyceride, increased secretion of VLDL, and
      increased hypertriglyceridemia.

PMID- 12177162
TI  - The murine macrophage apoB-48 receptor gene (Apob-48r): homology to the human
      receptor.
AB  - Previously we cloned the human macrophage apolipoprotein B-48 receptor (ApoB-48R)
      and documented its expression in human atherosclerotic foam cells (1). Now we
      have identified and characterized the murine macrophage apob-48r cDNA gene
      sequence and its chromosomal location. The cDNA (3,615 bp) -deduced amino acid
      (aa) sequence (942 aa) is approximately 45% identical to the human macrophage
      APOB-48R, but not to other known gene families. The murine Apob-48r gene, like
      the human APOB-48R gene, consists of four exons interrupted by three small
      introns and is syntenically located on chromosome 7. Functionally significant
      conserved domains include an N-terminal hydrophobic domain, a glycosaminoglycan
      attachment site, an N-glycosylation site, and an ExxxLL internalization motif C
      terminal to the putative internal transmembrane domain. Two conserved coiled-coil
      domains are likely involved in the spontaneous homodimerization that generates
      the active dimeric ligand binding species (mouse, approximately 190 kDa; human,
      approximately 200 kDa). Transfection of the murine apoB-48R into Chinese hamster
      ovary cells (CHOs) confers apoB-48R function: rapid, high-affinity, specific
      uptake of known triglyceride-rich lipoprotein ligands of the apoB-48R and, of
      note, uptake of the cholesteryl ester-rich apoB-48-containing very low density
      lipoproteins that accumulate in atherosclerosis-prone apoE-deficient mice. Uptake
      of these ligands by murine apoB-48R-transfected CHOs causes saturable, visible
      cellular triglyceride and cholesterol accumulation in vitro that resemble foam
      cells of atherosclerotic lesions. In aggregate, the data presented here and that
      previously published suggest that the apoE-independent murine apoB-48R pathway
      may contribute to the spontaneous development of atherosclerotic lesions rich in
      macrophage-derived foam cells observed in apoE-deficient mice, a murine model of
      human atherosclerosis.

PMID- 12177163
TI  - Limb malformations of rat fetuses exposed to a distal inhibitor of cholesterol
      biosynthesis.
AB  - Triparanol, an inhibitor of desmosterol Delta24 reductase, produces a high rate
      of limb malformations in rat fetuses exposed at gestational day 10 (gd 10) to a
      single oral dose (150-200 mg/kg) given to the pregnant dam. AY9944, another
      efficient distal inhibitor of cholesterol biosynthesis that blocks
      dehydrocholesterol Delta7 reductase, produces a similar degree of cholesterol
      depletion but fewer malformations. Gas liquid chromatography-mass spectrometry
      (GC-MS) profiling of the sterols in the serum of the dams and in extracted
      embryos shows that in addition to desmosterol Delta24 reductase inhibition the
      conversion of Delta8 to Delta7 unsaturated sterols is also blocked by Triparanol.
      Therefore, the inhibitor induces the accumulation of desmosterol (Delta8
      cholesten-3beta-ol, 8-dehydrocholesterol) and zymosterol (Delta8, Delta24
      cholestadien-3beta-ol) in embryo tissues. The high concentration of the
      teratogenic drug assayed in the embryos at three successive gestational days (10
      30 micro g/g) is thought to cause the blockade in both Delta24 reductase and
      Delta8-Delta7 isomerase, which results in the particular profile of aberrant
      sterols. Comparison of the animal model with human syndromes, including limb
      osseous and skeleton perturbations, suggests a combination of desmosterol and
      Delta8 unsaturated sterols as being involved in the deleterious influence on limb
      bone formation.

PMID- 12177164
TI  - Macrophage-specific expression of class A scavenger receptors in LDL receptor(-/
      ) mice decreases atherosclerosis and changes spleen morphology.
AB  - Class A scavenger receptors (SR-A) have been implicated in the atherogenic
      process, although there have been conflicting reports as to their specific effect
      on the development of lesions. In part, this discord may arise because of the
      variable contribution of SR-A in the several cell types known to express this
      protein. To determine the effects of macrophage-specific SR-A expression in the
      atherogenic process, transgenic mice were created using the chicken lysozyme
      (lyso) promoter to drive expression of bovine SR-A (bSR-A). To express this gene
      in an atherosclerosis-susceptible strain, bone marrow cells from transgenic and
      non-transgenic littermates were used to repopulate lethally-irradiated female LDL
      receptor (LDLr)(-/-) mice. Following hematopoietic engraftment, mice were placed
      on a diet enriched in saturated fat and cholesterol. After 8 weeks, there was a
      modest, but statistically significant reduction in serum total cholesterol in
      LDLr(-/-) mice repopulated with lyso-bSR-A transgenic cells, due to decreased LDL
      cholesterol. The extent of atherosclerosis was reduced in both cross-sectional
      analysis of the aortic root and en face analysis of the intimal surface of the
      aortic arch. In addition to changes in atherosclerosis, lyso-bSR-A repopulated
      LDLr(-/-) mice had a marked increase (3.6x) in spleen weights and a disruption of
      spleen white pulp formation. Therefore, macrophage-specific overexpression of SR
      A resulted in reduced atherosclerosis in two vascular beds, reduced serum
      cholesterol concentrations, and changed the morphology of the spleen.

PMID- 12177165
TI  - Reversibility of n-3 fatty acid deficiency-induced changes in dopaminergic
      neurotransmission in rats: critical role of developmental stage.
AB  - Previous investigations have shown that the lipid composition of cerebral
      membranes and dopaminergic neurotransmission are changed under chronic alpha
      linolenic acid diet deficiency in the rat. This study investigated whether these
      changes could be reversed and if the stage of brain maturation might play a role
      in the recovery process. The effects of reversion on the fatty acid (FA)
      composition and dopaminergic neurotransmission were studied in brain regions
      known to be affected by such deficiency (i.e., the prefrontal cortex and nucleus
      accumbens) in 2-month-old animals. Dopamine release under pharmacological
      stimulation was studied using a dual-probe microdialysis method. Vesicular
      monoamine transporters were studied using quantitative autoradiography. The
      reversal diet, with adequate levels of n-6 and n-3 polyunsaturated fatty acids
      (PUFAs), was given to deficient rats at different stages of development (0, 7,
      14, or 21 days of age). The results showed that when given during the lactating
      period, this diet was able to restore both the FA composition of brain membranes
      and the parameters of dopaminergic neurotransmission studied. However, when given
      from weaning, it allowed partial recovery of biochemical parameters but no
      recovery of neurochemical factors. The occurrence of profound n-3 PUFA deficiency
      during the lactating period could therefore be an environmental insult leading to
      irreversible damage to specific brain functions.

PMID- 12177166
TI  - Transcriptional activities of nuclear SREBP-1a, -1c, and -2 to different target
      promoters of lipogenic and cholesterogenic genes.
AB  - Recent studies on the in vivo roles of the sterol regulatory element binding
      protein (SREBP) family indicate that SREBP-2 is more specific to cholesterogenic
      gene expression whereas SREBP-1 targets lipogenic genes. To define the molecular
      mechanism involved in this differential regulation, luciferase-reporter gene
      assays were performed in HepG2 cells to compare the transactivities of nuclear
      SREBP-1a, -1c, and -2 on a battery of SREBP-target promoters containing sterol
      regulatory element (SRE), SRE-like, or E-box sequences. The results show first
      that cholesterogenic genes containing classic SREs in their promoters are
      strongly and efficiently activated by both SREBP-1a and SREBP-2, but not by SREBP
      1c. Second, an E-box containing reporter gene is much less efficiently activated
      by SREBP-1a and -1c, and SREBP-2 was inactive in spite of its ability to bind to
      the E-box. Third, promoters of lipogenic enzymes containing variations of SRE
      (SRE-like sequences) are strongly activated by SREBP-1a, and only modestly and
      equally by both SREBP-1c and -2. Finally, substitution of the unique tyrosine
      residue within the basic helix-loop-helix (bHLH) portion of nuclear SREBPs with
      arginine, the conserved residue found in all other bHLH proteins, abolishes the
      transactivity of all SREBPs for SRE, and conversely results in markedly increased
      activity of SREBP-1 but not activity of SREBP-2 for E-boxes. These data
      demonstrate the different specificity and affinity of nuclear SREBP-1 and -2 for
      different target DNAs, explaining a part of the mechanism behind the differential
      in vivo regulation of cholesterogenic and lipogenic enzymes by SREBP-1 and -2,
      respectively.

PMID- 12177167
TI  - Distribution of human plasma PLTP mass and activity in hypo- and
      hyperalphalipoproteinemia.
AB  - Plasma phospholipid transfer protein (PLTP) plays an important role in
      lipoprotein metabolism and reverse cholesterol transport. We have recently
      reported that plasma PLTP concentration correlates positively with plasma HDL
      cholesterol (HDL-C) but not with PLTP activity in healthy subjects. We have also
      shown that PLTP exists as active and inactive forms in healthy human plasma. In
      the present study, we measured plasma PLTP concentration and PLTP activity, and
      analyzed the distribution of PLTP in normolipidemic subjects (controls),
      cholesteryl ester transfer protein (CETP) deficiency, and hypo
      alphalipoproteinemia (hypo-ALP). Plasma PLTP concentration was significantly
      lower (0.7 +/- 0.4 mg/l, mean +/- SD, n = 9, P < 0.001) in the hypo-ALP subjects,
      and significantly higher (19.5 +/- 4.3 mg/l, n = 17, P < 0.001) in CETP
      deficiency than in the controls (12.4 +/- 2.3 mg/l, n = 63). In contrast, we
      observed no significant differences in plasma PLTP activity between controls,
      hypo-ALP subjects, and CETP deficiency (6.2 +/- 1.3, 6.1 +/- 1.8, and 6.8 +/- 1.2
      micro mol/ml/h, respectively). There was a positive correlation between PLTP
      concentration and plasma HDL-C (r = 0.81, n = 89, P < 0.001). By size exclusion
      chromatography analysis, we found that the larger PLTP containing particles
      without PLTP activity (inactive form of PLTP) were almost absent in the plasma of
      hypo-ALP subjects, and accumulated in the plasma of CETP deficiency compared with
      those of controls. These results indicate that the differences in plasma PLTP
      concentrations between hypo-ALP subjects, CETP deficiency, and controls are
      mainly due to the differences in the amount of the inactive form of PLTP.

PMID- 12177168
TI  - Activation of phospholipase D-2 by P2X(7) agonists in rat submandibular gland
      acini.
AB  - Exogenous ATP stimulated phospholipase D (PLD), but not sphingomyelinase in rat
      submandibular gland (SMG) acini. PLD activation was dependent upon extracellular
      Ca(2+) and did not involve intracellular Ca(2+) mobilization or phosphoinositide
      specific phospholipase C activation. ATP-stimulated PLD was attenuated by
      inhibition or downregulation of protein kinase C (PKC). PLD activation was fully
      blocked by the cytosolic phospholipase A(2) (PLA(2)) inhibitor ONO-RS-082 and
      partially attenuated by the selective Ca(2+)-dependent cytosolic PLA(2)
      inhibitor, arachidonyl trifluoromethylketone (AACOCF(3)), or by bromoenol
      lactone, an inhibitor of Ca(2+)-independent cytosolic PLA(2). Magnesium, which
      decreases the concentration of ATP(4-), and nickel, which blocks nonspecific
      cation channels coupled to purinergic receptors, inhibited PLD activation by ATP.
      Using reverse transcription-polymerase chain reaction and Northern blotting
      techniques, we demonstrated that the PLD isoform stimulated by ATP was PLD-2.
      Among various ATP analogs, only the P2Z/P2X(7) purinergic receptor agonist
      benzoyl-benzoyl ATP stimulated PLD-2. The response to ATP was inhibited by the
      nonselective P2X purinergic antagonist suramin and by oxidized ATP, a potent
      P2Z/P2X(7) receptor antagonist. It is concluded that in rat SMG acinar cells, PLD
      2 is upregulated by exogenous ATP through a mechanism involving Ca(2+) influx,
      cytosolic PLA(2), and PKC. Also, the data suggest an involvement of P2X(7)
      receptors in PLD-2 stimulation by ATP.

PMID- 12177169
TI  - Selective and independent associations of phospholipid transfer protein and
      hepatic lipase with the LDL subfraction distribution.
AB  - Phospholipid transfer protein (PLTP), hepatic lipase (HL), and lipoprotein lipase
      (LPL) have all been reported to be intricately involved in HDL metabolism but the
      effect of PLTP on the apolipoprotein B-containing lipoproteins relative to that
      of HL and LPL has not been established. Due to our previous observation of a
      positive correlation of PLTP activity with plasma apoB and LDL cholesterol, the
      relationship of PLTP with the LDL subfractions was investigated and compared with
      that of HL and LPL. Plasma lipoproteins from 50 premenopausal women were
      fractionated by density gradient ultracentrifugation. Correlations were
      calculated between the cholesterol concentration of each fraction and plasma
      PLTP, HL, and LPL activity. Plasma PLTP activity was highly, positively, and
      selectively correlated with the cholesterol concentration of the buoyant
      LDL/dense IDL fractions, yet demonstrated a complete absence of an association
      with the dense LDL fractions. In contrast, HL was positively correlated with the
      dense LDL fractions but showed no association with buoyant LDL. LPL was also
      positively correlated with several buoyant LDL fractions; however, the
      correlations were weaker than those of PLTP. PLTP and LPL were positively
      correlated and HL was negatively correlated with HDL fractions. The results
      suggest that PLTP and HL may be important and independent determinants of the LDL
      subpopulation density distributions.

PMID- 12177170
TI  - LDL and HDL enriched in triglyceride promote abnormal cholesterol transport.
AB  - Hypertriglyceridemia induces multiple changes in lipoprotein composition. Here we
      investigate how one of these modifications, triglyceride (TG) enrichment, affects
      HDL and LDL function when this alteration occurs under conditions in which more
      polar components can naturally re-equilibrate. TG-enriched lipoproteins were
      produced by co-incubating VLDL, LDL, and HDL with cholesteryl ester (CE) transfer
      protein. The resulting 2.5-fold increase in TG/CE ratio did not measurably alter
      the apoprotein composition of LDL or HDL, or modify LDL size. HDL mean diameter
      increased slightly from 9.1 to 9.4 nm. Modified LDL was internalized by
      fibroblasts normally, but its protein was degraded much less efficiently. This
      likely reflects an aberrant apolipoprotein B (apoB) conformation, as suggested by
      its resistance to V8 protease digestion and altered LDL electrophoretic mobility.
      TG-enriched LDL ineffectively down-regulated cholesterol biosynthesis compared
      with control LDL at the same protein concentration, but was equivalent in sterol
      regulation when compared on a cholesterol basis. TG-enriched HDL promoted greater
      net cholesterol efflux from cholesterol-loaded J774 cells. However, cholesterol
      associated with TG-enriched HDL was inefficiently esterified by
      lecithin:cholesterol acyltransferase, and TG-enriched HDLs were poor donors of CE
      to HepG2 hepatocytes by selective uptake. We conclude that TG-enrichment, in the
      absence of other significant alterations in lipoprotein composition, is
      sufficient to alter both cholesterol delivery and removal mechanisms. Some of
      these abnormalities may contribute to increased coronary disease in
      hypertriglyceridemia.

PMID- 12177171
TI  - PMA activation of macrophages alters macrophage metabolism of aggregated LDL.
AB  - Aggregation of LDL may contribute to its retention in atherosclerotic lesions.
      Previously, we showed that aggregated LDL induces and enters surface-connected
      compartments (SCCs) in human monocyte-derived macrophages by a process we have
      named patocytosis. Aggregated LDL was disaggregated and released from SCCs of
      macrophages when exposed to human lipoprotein-deficient serum. The serum factor
      that mediated aggregated LDL release and disaggregation was plasmin generated
      from plasminogen by macrophage urokinase plasminogen activator. We now show that
      activation of macrophages with PMA inhibits plasmin-mediated release of
      aggregated LDL from macrophages. With macrophage activation, plasminogen released
      about 60% less cholesterol and 63% less TCA-insoluble (125)I-aggregated LDL than
      when macrophages were not activated. Electron microscopy showed that PMA did not
      cause SCCs to close, which could have trapped aggregated LDL within the SCCs and
      limited protease access to aggregated LDL. Rather, PMA decreased macrophage
      generation of plasmin by 61%, and stimulated lysosomal degradation of aggregated
      LDL by more than 2-fold. Degradation was mediated by protein kinase C, shown by
      the finding that degradation was inhibited by the protein kinase C inhibitor
      Go6976. PMA-stimulated degradation of aggregated LDL was associated with a 3-fold
      increase in cholesterol esterification, consistent with hydrolysis and re
      esterification of aggregated LDL-derived cholesteryl ester. In conclusion,
      macrophage activation with PMA causes more of the aggregated LDL that enters
      macrophage SCCs to be metabolized by lysosomes. This results in more cholesterol
      to be stored in macrophages and less aggregated LDL to be available for plasmin
      mediated release from macrophage SCCs.

PMID- 12177172
TI  - Structure-function studies of apoA-I variants: site-directed mutagenesis and
      natural mutations.
AB  - Five mutants of apolipoprotein A-I (apoA-I), apoA-I(Delta63-73), apoA-I(Delta140
      150), apoA-I(63-73@140-150), apoA-I(R149V), and apoA-I(P143A) were compared with
      human plasma apoA-I for their ability to promote cholesterol and phospholipid
      efflux from HepG2 cells. A significantly lower capacity to promote cholesterol
      and phospholipid efflux was observed with lipid-free apoA-I(Delta63-73), while
      mutations apoA-I(Delta140-150) and apoA-I(P143A) affected phospholipid efflux
      only. When added as apoA-I/palmitoyloleoyl phosphatidylcholine (POPC) complex,
      mutations apoA-I(63-73@140-150) and apoA-I(Delta140-150) affected cholesterol
      efflux. None of the mutations affected alpha-helicity of the lipid-free mutants
      or their self-association. Five natural mutations of apoA-I, apoA-I(A95D), apoA-I
      (Y100H), apoA-I(E110K), apoA-I(V156E), and apoA-I (H162Q) were studied for their
      ability to bind lipids and promote cholesterol efflux. None of the mutations
      affected lipid-binding properties, cholesterol efflux, or alpha-helicity of lipid
      free mutants. Two mutations affected self-association of apoA-I: apoA-I(A95D) was
      more prone to self-association, while apoA-I(E100H) did not self-associate. The
      following conclusions could be made from the combined data: i) regions 210-243
      and 63-100 are the lipid-binding sites of apoA-I and are also required for the
      efflux of lipids to lipid-free apoA-I, suggesting that initial lipidation of apoA
      I is rate limiting in efflux; ii) in addition to the lipid-binding regions, the
      central region is important for cholesterol efflux to lipidated apoA-I,
      suggesting its possible involvement in interaction with cells.

PMID- 12177173
TI  - Glucosylceramide synthesis and synthase expression protect against ceramide
      induced stress.
AB  - Ceramides (Cers), critical for epidermal barrier function, also can inhibit
      keratinocyte proliferation, while glucosylceramides (GlcCers) exert pro-mitogenic
      effects. Since alterations in Cer-to-GlcCer ratios appear to modulate cellular
      growth versus apoptosis, we assessed whether keratinocytes up-regulate GlcCer
      synthesis as a protective mechanism against Cer-induced stress. Exogenous
      sphingomyelinase (SMase) treatment of cultured human keratinocytes (CHK)
      initially decreased proliferation and cellular sphingomyelin (50-60% decrease; P
      < 0.001), and increased Cer levels (6.1- to 6.8-fold; P < 0.001). Proliferation
      recovered to normal rates by 24 h, in parallel with increased cellular GlcCer.
      Both GlcCer synthesis and GlcCer synthase activity increased significantly by 8 h
      following SMase (8.2- and 2.4-fold, respectively; P < 0.01 each vs. control),
      attributed to antecedent increases in GlcCer synthase mRNA and protein
      expression. Further evidence that GlcCer production is responsible for normalized
      CHK proliferation includes: a) attenuation of SMase-induced inhibition of
      proliferation by exogenous GlcCer; and b) enhancement of the SMase effect in
      cells cotreated with the GlcCer synthase inhibitor, PDMP (D-threo-1-phenyl
      2(decanoylamino)-3-morpholino-1-propanol). Finally, although proliferation in
      immortalized, nontransformed keratinocytes (HaCaT) also was inhibited by SMase,
      HaCaT cells that overexpress GlcCer synthase were resistant to this effect. Thus,
      SMase-induced stress initiates a response in keratinocytes that includes
      upregulation of GlcCer synthesis which may protect against the deleterious
      effects of excess Cer.

PMID- 12177174
TI  - Regulation of MTP expression in developing swine.
AB  - To define the developmental expression of microsomal triglyceride transfer
      protein (MTP) large subunit mRNA and protein, samples of small intestine and
      liver were collected from 40-day gestation fetal, 2-day-old newborn, 3-week-old
      suckling, and 2-month-old weanling swine. In fetal animals, MTP mRNA expression
      was high in intestine and liver. Postnatally, jejunal expression paralleled the
      intake of a high-fat breast milk diet and declined after weaning. Ileal
      expression was comparable with that of jejunum in 2-day-old animals, but declined
      to low levels afterward. Hepatic expression declined postnatally and remained
      low. MTP protein expression generally paralleled mRNA expression, except in fetal
      intestine in which no 97 kDa protein was detected. In 2-day-old piglets, a high
      triacylglycerol diet increased jejunal and ileal MTP mRNA levels, as compared to
      a low-triacylglycerol diet. To test the roles of glucocorticoids and fatty acids
      in MTP regulation, a newborn swine enterocyte cell line (IPEC-1) was used. Except
      at day 2 of differentiation, dexamethasone did not influence MTP expression.
      Fatty acids either up-regulated or down-regulated MTP expression, depending on
      the specific fatty acid and duration of exposure. Although programmed genetic
      cues regulate MTP expression during development, clearly the amount and fatty
      acid composition of dietary lipid also play regulatory roles.

PMID- 12177175
TI  - Anti-obesity effect of dietary diacylglycerol in C57BL/6J mice: dietary
      diacylglycerol stimulates intestinal lipid metabolism.
AB  - We examined the long-term effects of dietary diacylglycerol (DG) and
      triacylglycerol (TG) with similar fatty acid compositions on the development of
      obesity in C57BL/6J mice. We also analyzed the expression of genes involved in
      lipid metabolism at an early stage of obesity development in these mice. Compared
      with mice fed the high-TG diet, mice fed the high-DG diet accumulated
      significantly less body fat during the 8-month study period. Within the first 10
      days, dietary DG stimulated beta-oxidation and lipid metabolism-related gene
      expression, including acyl-CoA oxidase, medium-chain acyl-CoA dehydrogenase, and
      uncoupling protein-2 in the small intestine but not in the liver, skeletal
      muscle, or brown adipose tissue, suggesting the predominant contribution of
      intestinal lipid metabolism to the effects of DG. Furthermore, analysis of
      digestion products of [(14)C]DG and those of [(14)C]TG revealed that the
      radioactivity levels detected in fatty acid, 1-monoacylglycerol, and 1,3-DG in
      intestinal mucosa were significantly higher after intrajejunal injection of DG
      rather than TG. Thus, dietary DG reduces body weight gain that accompanies the
      stimulation of intestinal lipid metabolism, and these effects may be related to
      the characteristic metabolism of DG in the small intestine.

PMID- 12177176
TI  - Ileal bile acid transporter inhibition, CYP7A1 induction, and antilipemic action
      of 264W94.
AB  - 264W94 was designed to inhibit the ileal bile acid transporter (IBAT). Evaluated
      in vitro, 264W94 dose-dependently inhibited sodium-dependent uptake of 10 micro M
      [(3)H]taurocholic acid (TC) by rat and monkey brush border membrane vesicles with
      IC(50)s of 0.24 micro M and 0.41 micro M, and had a competitive profile with K(i)
      of 0.2 micro M against TC in Chinese hamster ovary cells expressing human IBAT.
      In distal ileum in situ, 1-10 micro M of 264W94 rapidly decreased uptake of 3mM
      TC by 24-39%, with corresponding decreases in biliary recovery. In rats and mice
      in vivo, oral 264W94 decreased absorption of TC analog, 23,25-(75)Se-homocholic
      acid taurine ((75)SeHCAT; quantitated in feces), with ED(30) of 0.02 mg/kg bid.
      (75)SeHCAT traced through the GI-tract revealed that peak (97%) inhibition of
      (75)SeHCAT absorption by the distal quarter of small intestine occurred at 4 h
      after single dose of 264W94 (0.1 mg/kg). Inhibition of IBAT by 264W94 in rats was
      associated with compensatory, same-day, 4-fold induction of hepatic cholesterol
      7alpha-hydroxylase (CYP7A1) activity, exhibiting normal diurnal fluctuation for 3
      days of dosing. In diet induced hypercholesterolemic rats, 264W94 (0.03-1.0 mg/kg
      bid) dose-dependently reduced serum LDL+VLDL cholesterol up to 61%. In
      conclusion, 264W94 is a potent new cholesterol lowering agent that acts through
      inhibition of IBAT and exhibits activity in a human model.

PMID- 12177177
TI  - Acute changes in triacylglycerol lipase activity of human adipose tissue during
      exercise.
AB  - Although physical exercise is known to increase adipose tissue lipolysis, its
      effect on the activity of triacylglycerol (TG) lipase, the enzyme regulating TG
      breakdown, is not known. The aim of the present study was to monitor the acute
      changes in TG lipase activity of adipose tissue induced during moderate exercise.
      For this purpose a new assay, sensitive to the phosphorylation state of the
      enzyme, was developed. Ten young sedentary men cycled for 30 min at a heart rate
      of 120-130 beats min(-1). Needle adipose tissue biopsy was performed from the
      buttock area at rest, at 5, 15, and 30 min of exercise, as well as at 15 min of
      passive recovery. Five other men served as controls by being biopsied as above
      without exercising. TG lipase activity was determined by measuring the decrease
      of endogenous TG concentration during incubation of the homogenized tissue. TG
      lipase activity increased 6.4-fold above baseline at 5 min of exercise (P <
      0.001) and fell gradually afterwards, whereas it did not change significantly in
      the control group. In conclusion, our data show that TG lipase activity in human
      adipose tissue peaks early during exercise and subsequently decreases despite the
      maintenance of the physical stimulus.

PMID- 12177178
TI  - Recovery of gangliosides from aqueous solutions on styrene-divinylbenzene
      copolymer columns.
AB  - An investigation was made using a styrene-divinylbenzene copolymer as a solid
      phase sorbent to recover gangliosides from aqueous solutions. A comparison with
      octadecyl-bonded (C18) silica gel showed that the general procedure used to
      purify gangliosides on C18 silica gel could be used with the copolymer. The yield
      of gangliosides depended on various parameters such as the composition of the
      conditioning solution, the salt concentration of the loading solution, and the
      amount of applied gangliosides per gram of copolymer. In optimal conditions, the
      recovery of gangliosides and other lipids present in the upper phases of
      partition was higher than 95%. Using radiolabeled gangliosides, it was found that
      gangliosides present in serum-containing medium could also be quantitatively
      recovered on copolymer, provided the medium was diluted with an equal volume of
      methanol prior to its application onto the column. The major advantage of the
      copolymer is its high stability in acidic or alkaline conditions that allows
      multiple cycles of cleaning and reconditioning of the sorbent without alteration
      of its chromatographic properties.

PMID- 12177179
TI  - Synthesis and biochemical properties of a new photoactivatable cholesterol analog
      7,7-azocholestanol and its linoleate ester in Chinese hamster ovary cell lines.
AB  - We report the chemical synthesis of a new photoactivatable cholesterol analog 7,7
      azocholestanol (AC) and its linoleate ester (ACL). We also examined the
      biochemical properties of the sterol and its ester by employing several different
      mutant Chinese hamster ovary (CHO) cell lines with defined abnormalities in
      cholesterol metabolism as tools. AC mimics cholesterol in supporting the growth
      of a mutant cell line (M19) that requires cholesterol for growth. In normal
      cells, tritiated ACL present in low-density lipoprotein (LDL) was hydrolyzed and
      reesterified in a manner similar to tritiated cholesteryl linoleate (CL) in LDL.
      Also, in the mutant cell line (AC29) lacking the enzyme acyl-coenzyme
      A:cholesterol acyltransferase or in the mutant cell line (CT60) defective in the
      Niemann-Pick type C1 protein, the hydrolysis of ACL in LDL was normal, but the
      reesterification of the liberated AC was defective. Therefore, the metabolism of
      ACL in LDL is very similar to that of CL in LDL. Tritium-labeled AC delivered to
      intact CHO cells as a cyclodextrin complex was shown to photoaffinity label
      several discrete polypeptides, including caveolin-1. These results demonstrate AC
      as an effective reagent for studying cholesterol-protein interactions involved in
      intracellular cholesterol trafficking.

PMID- 12177180
TI  - Precise firing events are conserved across neurons.
AB  - Sensory neurons can respond to dynamic stimuli with temporally precise firing
      events. In the lateral geniculate nucleus (LGN) of the thalamus, we found
      previously that when a flickering visual stimulus was repeated, individual cells
      fired action potentials at the same time in every trial to within 1 msec. We now
      show that these precise firing events are also reproducible across cells of the
      same class. Therefore, the mechanisms for producing precise timing must be
      conserved within a cell class. Our results further suggest that cortical neurons
      would require only a few generic processing mechanisms to extract the fine
      temporal information available in their LGN inputs.

PMID- 12177181
TI  - Spontaneous versus reinforced olfactory discriminations.
AB  - When the major response domains in the rat olfactory bulb that are evoked by
      odorant enantiomers are compared, some of these odorant pairs do not show
      significantly different activity patterns. Such pairs are not spontaneously
      discriminated in a behavioral test. We show here that even these similar odorants
      appear to evoke different activity patterns when every data point in a glomerular
      activity array is compared. These odorants also can be discriminated if they are
      subjected to differential reinforcement. These data suggest that the method
      chosen to assess olfactory discrimination will reveal different olfactory
      capabilities of rats. The small differences in glomerular activity that probably
      exist between any pair of odorants may serve as a basis for odor discrimination
      when rats are differentially reinforced, thereby establishing the remarkable
      limits of rat olfactory perception. At the same time, the major differences in
      glomerular responses appear to serve as the normal basis for spontaneous odor
      discrimination.

PMID- 12177182
TI  - Serotonin receptor activation inhibits sodium current and dendritic excitability
      in prefrontal cortex via a protein kinase C-dependent mechanism.
AB  - The serotonin (5-HT) innervation of the prefrontal cortex (PFC) exerts a powerful
      modulatory influence on neuronal activity in this cortical region, although the
      mechanisms through which 5-HT modulates cellular activity are unclear. Voltage
      dependent Na+ channels are one potential target of 5-HT receptor signaling that
      have wide-ranging effects on activity. Molecular and electrophysiological studies
      were used to test this potential linkage. Single cell RT-PCR profiling revealed
      that the vast majority of pyramidal neurons expressed detectable levels of 5-HT2a
      and/or 5-HT2c receptor mRNA with half of the cells expressing both mRNAs. Whole
      cell voltage-clamp recordings of dissociated pyramidal neurons showed that 5
      HT2a/c receptor activation reduced rapidly inactivating Na+ currents by reducing
      maximal current amplitude and shifting fast inactivation voltage dependence.
      These effects were mediated by G(q) activation of phospholipase C, leading to
      activation of protein kinase C (PKC). 5-HT2a/c receptor stimulation also reduced
      the amplitude of persistent Na+ current without altering its activation voltage
      dependence. This modulation was also mediated by PKC. Although 5-HT(2a,c)
      receptor activation did not affect somatic action potentials of layer V pyramidal
      neurons in PFC slices, it did reduce the amplitude of action potentials
      backpropagating into the apical dendrite. These findings show that 5-HT2a,c
      receptor activation reduces dendritic excitability and may negatively modulate
      activity-dependent dendritic synaptic plasticity.

PMID- 12177183
TI  - Neuronal T-type alpha 1H calcium channels induce neuritogenesis and expression of
      high-voltage-activated calcium channels in the NG108-15 cell line.
AB  - Neuronal differentiation involves both morphological and electrophysiological
      changes, which depend on calcium influx. Voltage-gated calcium channels (VGCCs)
      represent a major route for calcium entry into neurons. The recently cloned low
      voltage-activated T-type calcium channels (T-channels) are the first class of
      VGCCs functionally expressed in most developing neurons, as well as in
      neuroblastoma cell lines, but their roles in neuronal development are yet
      unknown. Here, we document the part played by T-channels in neuronal
      differentiation. Using NG108-15, a cell line that recapitulates early steps of
      neuronal differentiation, we demonstrate that blocking T-currents by nickel,
      mibefradil, or the endogenous cannabinoid anandamide prevents neuritogenesis
      without affecting neurite outgrowth. Similar results were obtained using
      antisense oligodeoxynucleotides directed against the alpha1H T-channel subunit.
      Furthermore, we describe that inhibition of alpha1H T-channel activity impairs
      concomitantly, but independently, both high-voltage-activated calcium channel
      expression and neuritogenesis, providing strong evidence for a dual role of T
      channels in both morphological and electrical changes at early stages of neuronal
      differentiation.

PMID- 12177184
TI  - Glycogen synthase kinase-3 is activated in neuronal cells by Galpha12 and
      Galpha13 by Rho-independent and Rho-dependent mechanisms.
AB  - Glycogen synthase kinase-3 (GSK-3) was generally considered a constitutively
      active enzyme, only regulated by inhibition. Here we describe that GSK-3 is
      activated by lysophosphatidic acid (LPA) during neurite retraction in rat
      cerebellar granule neurons. GSK-3 activation correlates with an increase in GSK-3
      tyrosine phosphorylation. In addition, LPA induces a GSK-3-mediated
      hyperphosphorylation of the microtubule-associated protein tau. Inhibition of GSK
      3 by lithium partially blocks neurite retraction, indicating that GSK-3
      activation is important but not essential for the neurite retraction progress.
      GSK-3 activation by LPA in cerebellar granule neurons is neither downstream of
      Galpha(i) nor downstream of Galpha(q)/phospholipase C, suggesting that it is
      downstream of Galpha12/13. Overexpression of constitutively active Galpha12
      (Galpha12QL) and Galpha13 (Galpha13QL) in Neuro2a cells induces upregulation of
      GSK-3 activity. Furthermore, overexpression of constitutively active RhoA
      (RhoAV14) also activates GSK-3 However, the activation of GSK-3 by Galpha13 is
      blocked by coexpression with C3 transferase, whereas C3 does not block GSK-3
      activation by Galpha12. Thus, we demonstrate that GSK-3 is activated by both
      Galpha12 and Galpha13 in neuronal cells. However, GSK-3 activation by Galpha13 is
      Rho-mediated, whereas GSK-3 activation by Galpha12 is Rho-independent. The
      results presented here imply the existence of a previously unknown mechanism of
      GSK-3 activation by Galpha12/13 subunits.

PMID- 12177185
TI  - Complex gangliosides at the neuromuscular junction are membrane receptors for
      autoantibodies and botulinum neurotoxin but redundant for normal synaptic
      function.
AB  - One specialization of vertebrate presynaptic neuronal membranes is their
      multifold enrichment in complex gangliosides, suggesting that these
      sialoglycolipids may play a major functional role in synaptic transmission. We
      tested this hypothesis directly by studying neuromuscular synapses of mice
      lacking complex gangliosides attributable to deletion of the gene coding for
      beta1,4 GalNAc-transferase (GM2/GD2 synthase), which catalyzes an early step in
      ganglioside synthesis. Our studies show that complex gangliosides are
      surprisingly redundant for regulated neurotransmitter release under normal
      physiological conditions. In contrast, we show that they are membrane receptors
      for both the paralytic botulinum neurotoxin type-A and human neuropathy
      associated anti-ganglioside autoantibodies that arise through molecular mimicry
      with microbial structures. These data prove the critical importance of complex
      gangliosides in mediating pathophysiological events at the neuromuscular synapse.

PMID- 12177186
TI  - Modulation of presynaptic calcium transients by metabotropic glutamate receptor
      activation: a differential role in acute depression of synaptic transmission and
      long-term depression.
AB  - Activation of group I metabotropic glutamate receptors (mGluRs) can induce acute
      depression of excitatory synaptic transmission and long-term depression (LTD) in
      area CA1 of the rat hippocampus. The underlying mechanisms for both forms of
      depression are unknown. By measuring presynaptic calcium transients, we show that
      a reduction in the stimulation-induced presynaptic calcium rise that triggers
      vesicular release causes the acute depression of transmission by group I mGluRs.
      In contrast, the mechanism underlying mGluR-induced LTD does not involve a
      persistent change in stimulation-induced calcium influx. However, analysis of
      paired-pulse facilitation experiments suggests a presynaptic location for
      expression of this form of LTD. Furthermore, we show that mGluR-induced LTD can
      be completely blocked by a specific mGluR5 antagonist, whereas mGluR1 antagonists
      strongly attenuate the acute depression of transmission. These results support
      the hypothesis that the acute depression of transmission caused by activation of
      group I mGluRs involves regulation of stimulation-induced presynaptic calcium
      transients, whereas mGluR-induced LTD involves a distinct presynaptic modulation
      downstream of calcium influx.

PMID- 12177187
TI  - K+-dependent Na+/Ca2+ exchange is a major Ca2+ clearance mechanism in axon
      terminals of rat neurohypophysis.
AB  - Two different families of Na+/Ca2+ exchangers, K+-independent NCX and K+
      dependent NCKX, are known. Exploiting the outward K+ gradient, NCKX is able to
      extrude Ca2+ more efficiently than NCX, even when the Na+ gradient is reduced.
      The NCKX, which was originally thought to be limited to the retinal
      photoreceptor, was shown recently to be widely distributed in the brain. We
      investigated the contribution of Na+/Ca2+ exchange to Ca2+ clearance mechanisms
      in neurohypophysial (NHP) axon terminals, using patch-clamp and microfluorometry
      techniques. In the presence of internal K+, Ca2+ decay was significantly slowed
      by the removal of external Na+, indicative of the role of Na+/Ca2+ exchange. As
      internal [K+] was decreased, Ca2+ decay rate and its dependence on Na+ were
      greatly attenuated. In the absence of internal K+, Ca2+ decay rate was little
      affected by Na+ removal. Quantitative analysis using Ca2+ decay rate constant
      indicated that >60% of Ca2+ extrusion is mediated by Na+/Ca2+ exchange when peak
      [Ca2+] level is higher than 500 nm, and approximately 90% of Na+/Ca2+ exchange
      activity is K+ dependent. In situ hybridization confirmed the expression of NCKX2
      transcripts in the supraoptic nucleus in which soma of NHP axon terminals are
      located. To our knowledge, this is the first report to show the significant role
      of K+-dependent Na+/Ca2+ exchange in neuronal cells other than photoreceptors.
      Considering that axon terminals are subject to an invasion by high-frequency Na+
      spikes, which may lower Na+ gradients, the presence of NCKX may have a functional
      significance in intracellular Ca2+ regulation.

PMID- 12177188
TI  - Experimental parkinsonism alters endocannabinoid degradation: implications for
      striatal glutamatergic transmission.
AB  - Cannabinoid receptors and their endogenous ligands have been recently identified
      in the brain as potent inhibitors of neurotransmitter release. Here we show that,
      in a rat model of Parkinson's disease induced by unilateral nigral lesion with 6
      hydroxydopamine (6-OHDA), the striatal levels of anandamide, but not that of the
      other endocannabinoid 2-arachidonoylglycerol, were increased. Moreover, we
      observed a decreased activity of the anandamide membrane transporter (AMT) and of
      the anandamide hydrolase [fatty acid amide hydrolase (FAAH)], whereas the binding
      of anandamide to cannabinoid receptors was unaffected. Spontaneous glutamatergic
      activity recorded from striatal spiny neurons was higher in 6-OHDA-lesioned rats.
      Inhibition of AMT by N-(4-hydroxyphenyl)-arachidonoylamide (AM-404) or by VDM11,
      or stimulation of the cannabinoid CB1 receptor by HU-210 reduced glutamatergic
      spontaneous activity in both naive and 6-OHDA-lesioned animals to a similar
      extent. Conversely, the FAAH inhibitors phenylmethylsulfonyl fluoride and methyl
      arachidonoyl fluorophosphonate were much more effective in 6-OHDA-lesioned
      animals. The present study shows that inhibition of anandamide hydrolysis might
      represent a possible target to decrease the abnormal cortical glutamatergic drive
      in Parkinson's disease.

PMID- 12177189
TI  - Axonal projection, input and output synapses, and synaptic physiology of Cajal
      Retzius cells in the developing rat neocortex.
AB  - Cajal-Retzius (CR) cells are among the earliest generated neurons and are thought
      to play a role in corticogenesis and early neuronal migration. However, the role
      of CR cells in an early cortical microcircuit is still rather unclear. We
      therefore have investigated the morphology and physiology of CR cells by using
      whole-cell patch-clamp recordings combined with intracellular biocytin filling in
      acute brain slices of postnatal day 5-11 rats. CR cells are characterized by a
      long horizontally oriented dendrite; the axonal collaterals form a dense
      horizontally oriented plexus in layer 1 and to a certain extent in layer 2/3,
      projecting over >2 mm of cortical surface. The bouton density is relatively high,
      and synaptic contacts are established preferentially with dendritic spines or
      shafts of excitatory neurons, presumably terminal tuft dendrites of pyramidal
      neurons. In turn, CR cells receive dense GABAergic and non-GABAergic input on
      somata, dendritic shafts, and spine-like appendages. Extracellular stimulation in
      layer 1 could activate both GABAergic and glutamatergic synaptic inputs. The
      GABAergic response was blocked by the GABA(A) receptor antagonist bicuculline.
      The glutamatergic response was mediated solely by NMDA receptors and was highly
      sensitive to ifenprodil, indicating that it was mediated mainly via NR1/NR2B
      subunit-containing receptors. NMDA EPSPs were apparent in 1 mm extracellular
      Mg2+, suggesting that this pure NMDA synapse is not silent functionally.
      Together, the long-range horizontal projection of the axon, the high density of
      synaptic boutons, and the functional synaptic input of CR cells suggest that they
      are an integral part of an early cortical network.

PMID- 12177190
TI  - Neuroprotective effects of glial cell line-derived neurotrophic factor mediated
      by an adeno-associated virus vector in a transgenic animal model of amyotrophic
      lateral sclerosis.
AB  - Amyotrophic lateral sclerosis (ALS) is a relentlessly progressive lethal disease
      that involves selective annihilation of motoneurons. Glial cell line-derived
      neurotrophic factor (GDNF) is proposed to be a promising therapeutic agent for
      ALS and other motor neuron diseases. Because adeno-associated virus (AAV) has
      been developed as an attractive gene delivery system with proven safety, we
      explored the therapeutic efficacy of intramuscular delivery of the GDNF gene
      mediated by an AAV vector (AAV-GDNF) in the G93A mouse model of ALS. We show here
      that AAV-GDNF leads to substantial and long-lasting expression of transgenic GDNF
      in a large number of myofibers with its accumulation at the sites of
      neuromuscular junctions. Detection of GDNF labeled with FLAG in the anterior horn
      neurons, but not beta-galactosidase expressed as a control, indicates that most
      of the transgenic GDNF observed there is retrogradely transported GDNF protein
      from the transduced muscles. This transgenic GDNF prevents motoneurons from their
      degeneration, preserves their axons innervating the muscle, and inhibits the
      treated-muscle atrophy. Furthermore, four-limb injection of AAV-GDNF postpones
      the disease onset, delays the progression of the motor dysfunction, and prolongs
      the life span in the treated ALS mice. Our finding thus indicates that AAV
      mediated GDNF delivery to the muscle is a promising means of gene therapy for
      ALS.

PMID- 12177191
TI  - VGF is required for obesity induced by diet, gold thioglucose treatment, and
      agouti and is differentially regulated in pro-opiomelanocortin- and neuropeptide
      Y-containing arcuate neurons in response to fasting.
AB  - Targeted deletion of the gene encoding the neuronal and neuroendocrine secreted
      polypeptide VGF (nonacronymic) produces a lean, hypermetabolic mouse. Consistent
      with this phenotype, VGF mRNA levels are regulated in the hypothalamic arcuate
      nucleus in response to fasting. To gain insight into the site(s) and mechanism(s)
      of action of VGF, we further characterized VGF expression in the hypothalamus.
      Double-label studies indicated that VGF and pro-opiomelanocortin were coexpressed
      in lateral arcuate neurons in the fed state, and that VGF expression was induced
      after fasting in medial arcuate neurons that synthesize neuropeptide Y (NPY).
      Like NPY, VGF mRNA induction in this region of the hypothalamus in fasted mice
      was inhibited by exogenous leptin. In leptin-deficient ob/ob and receptor-mutant
      db/db mice, VGF mRNA levels in the medial arcuate were elevated. To identify
      neural pathways that are functionally compromised by Vgf ablation, VGF mutant
      mice were crossed with obese A(y)/a (agouti) and ob/ob mice. VGF deficiency
      completely blocked the development of obesity in A(y)/a mice, whereas deletion of
      Vgf in ob/ob mice attenuated weight gain but had no impact on adiposity.
      Hypothalamic levels of NPY and agouti-related polypeptide mRNAs in both double
      mutant lines were dramatically elevated 10- to 15-fold above those of wild-type
      mice. VGF-deficient mice were also found to resist diet- and gold thioglucose
      induced obesity. These data and the susceptibility of VGF mutant mice to
      monosodium glutamate-induced obesity are consistent with a role for VGF in
      outflow pathways, downstream of hypothalamic and/or brainstem melanocortin 4
      receptors, that project via the autonomic nervous system to peripheral metabolic
      tissues and regulate energy homeostasis.

PMID- 12177192
TI  - Synaptic targeting of N-type calcium channels in hippocampal neurons.
AB  - N-type calcium (Ca2+) channels play a critical role in synaptic function, but the
      mechanisms responsible for their targeting in neurons are poorly understood. N
      type channels are formed by an alpha(1B) (Ca(V)2.2) pore-forming subunit
      associated with beta and alpha2delta auxiliary subunits. By expressing epitope
      tagged recombinant alpha1B subunits in rat hippocampal neuronal cultures, we
      demonstrate here that synaptic targeting of N-type channels depends on neuronal
      contacts and synapse formation. We also establish that the C-terminal 163 aa
      (2177-2339) of the alpha1B-1 (Ca(V)2.2a) splice variant contain sequences that
      are both necessary and sufficient for synaptic targeting. By site-directed
      mutagenesis, we demonstrate that postsynaptic density-95/discs large/zona
      occludens-1 and Src homology 3 domain-binding motifs located within this region
      of the alpha1B subunit (Maximov et al., 1999) act as synergistic synaptic
      targeting signals. We also show that the recombinant modular adaptor proteins
      Mint1 and CASK colocalize with N-type channels in synapses. We found that the
      alpha1B-2 (Ca(V)2.2b) splice variant is restricted to soma and dendrites and
      postulated that somatodendritic and axonal/presynaptic isoforms of N-type
      channels are generated via alternative splicing of alpha1B C termini. These data
      lead us to propose that during synaptogenesis, the alpha1B-1 (Ca(V)2.2a) splice
      variant of the N-type Ca2+ channel pore-forming subunit is recruited to
      presynaptic locations by means of interactions with modular adaptor proteins
      Mint1 and CASK. Our results provide a novel insight into the molecular mechanisms
      responsible for targeting of Ca2+ channels and other synaptic proteins in
      neurons.

PMID- 12177193
TI  - Two heteromeric Kv1 potassium channels differentially regulate action potential
      firing.
AB  - Low-threshold voltage-gated potassium currents (I(LT)) activating close to
      resting membrane potentials play an important role in shaping action potential
      (AP) firing patterns. In the medial nucleus of the trapezoid body (MNTB), I(LT)
      ensures generation of single APs during each EPSP, so that the timing and pattern
      of AP firing is preserved on transmission across this relay synapse (calyx of
      Held). This temporal information is critical for computation of sound location
      using interaural timing and level differences. I(LT) currents are generated by
      dendrotoxin-I-sensitive, Shaker-related K+ channels; our immunohistochemistry
      confirms that MNTB neurons express Kv1.1, Kv1.2, and Kv1.6 subunits. We used
      subunit-specific toxins to separate I(LT) into two components, each contributing
      approximately one-half of the total low-threshold current: (1) I(LTS), a
      tityustoxin-Kalpha-sensitive current (TsTX) (known to block Kv1.2 containing
      channels), and (2) I(LTR), an TsTX-resistant current. Both components were
      sensitive to the Kv1.1-specific toxin dendrotoxin-K and were insensitive to
      tetraethylammonium (1 mm). This pharmacological profile excludes homomeric Kv1.1
      or Kv1.2 channels and is consistent with I(LTS) channels being Kv1.1/Kv1.2
      heteromers, whereas I(LTR) channels are probably Kv1.1/Kv1.6 heteromers. Although
      they have similar kinetic properties, I(LTS) is critical for generating the
      phenotypic single AP response of MNTB neurons. Immunohistochemistry confirms that
      Kv1.1 and Kv1.2 (I(LTS) channels), but not Kv1.6, are concentrated in the first
      20 microm of MNTB axons. Our results show that heteromeric channels containing
      Kv1.2 subunits govern AP firing and suggest that their localization at the
      initial segment of MNTB axons can explain their dominance of AP firing behavior.

PMID- 12177194
TI  - Mitochondrial Ca2+ uptake regulates the excitability of myenteric neurons.
AB  - We investigated the role of mitochondria in the regulation of intracellular Ca2+
      ([Ca2+]i) and excitability of myenteric neurons in guinea pig ileum, using
      microelectrodes and fura-2 [Ca2+]i measurements. In AH/Type-II neurons, action
      potentials evoke ryanodine-sensitive increases in [Ca2+]i that activate Ca2+
      dependent K+ channels and slow afterhyperpolarizations (AH) lasting approximately
      15 sec. Exposure to the protonophore carbonyl cyanide p
      (trifluoromethoxy)phenylhydrazone (FCCP; 1 microm) had no significant effect on
      the membrane potential or resting [Ca2+]i. However, action potentials elicited in
      the presence of FCCP triggered a sustained (>5 min) increase in [Ca2+]i and a
      compound hyperpolarization (13.4 +/- 1.5 mV). The respiratory chain blockers
      antimycin A and rotenone (10 microm) had similar effects that developed more
      slowly. Depletion of the intracellular Ca2+ stores with thapsigargin (2 microm)
      or ryanodine (10 microm) greatly attenuated the hyperpolarization caused by FCCP.
      S/Type-I neurons that do not have AH were hyperpolarized by mitochondrial
      inhibition independently of action potentials. Blockade of the F0F1 ATPase by
      oligomycin (10 microm) had variable effects on myenteric neurons. The majority of
      AH/Type-II neurons were hyperpolarized by oligomycin, most likely by activating
      ATP-dependent K+ channels. This hyperpolarization was not triggered by action
      potential firing and not accompanied by an increase in [Ca2+]i. MitoTracker
      staining revealed a dense mitochondrial network particularly in myenteric AH/Type
      II neurons, supporting the importance of mitochondrial Ca2+ buffering in this
      subset of neurons. The data indicate that mitochondrial uptake of Ca2+ released
      from the endoplasmic reticulum sets [Ca2+]i and the activity of Ca2+-dependent
      conductances, thus regulating the excitability of myenteric neurons.

PMID- 12177195
TI  - Protective role of phosphorylation in turnover of glial fibrillary acidic protein
      in mice.
AB  - Glial fibrillary acidic protein (GFAP), the principal intermediate filament (IF)
      protein of mature astrocytes in the CNS, plays specific roles in astrocyte
      functions. GFAP has multiple phosphorylation sites at its N-terminal head domain.
      To examine the role of phosphorylation at these sites, we generated a series of
      substitution mutant mice in which phosphorylation sites (Ser/Thr) were replaced
      by Ala, in different combinations. Gfap(hm3/hm3) mice carrying substitutions at
      all five phosphorylation sites showed extensive decrease in both filament
      formation and amounts of GFAP. Gfap(hm1/hm1) and Gfap(hm2/hm2) mice, which carry
      substitutions at three of five sites and in different combinations, showed
      differential phenotypes. Although Gfap(hm3/hm3) mice retained GFAP filaments in
      Bergmann glia in the cerebellum, the (Gfap(hm3/hm3):Vim(-/-)) mice lacked GFAP
      filaments. Pulse-chase experiments of cultured astrocytes indicated that the Hm3
      GFAP encoded by Gfap(hm3) was unstable particularly in the absence of vimentin,
      another IF protein. These results revealed the role of phosphorylation in
      turnover of GFAP and a synergistic role of GFAP and vimentin in the dynamics of
      glial filaments. The data further suggest that each of the phosphorylated sites
      has a distinct impact on the dynamics of GFAP.

PMID- 12177196
TI  - Kalirin Dbl-homology guanine nucleotide exchange factor 1 domain initiates new
      axon outgrowths via RhoG-mediated mechanisms.
AB  - The large multidomain Kalirin and Trio proteins containing dual Rho GTPase
      guanine nucleotide exchange factor (GEF) domains have been implicated in the
      regulation of neuronal fiber extension and pathfinding during development. In
      mammals, Kalirin is expressed predominantly in the nervous system, whereas Trio,
      broadly expressed throughout the body, is expressed at a lower level in the
      nervous system. To evaluate the role of Kalirin in fiber initiation and
      outgrowth, we microinjected cultured sympathetic neurons with vectors encoding
      Kalirin or with Kalirin antisense oligonucleotides, and we assessed neuronal
      fiber growth in a serum-free, satellite cell-free environment. Kalirin antisense
      oligonucleotides blocked the continued extension of preexisting axons. Kalirin
      overexpression induced the prolific sprouting of new axonal fibers that grew at
      the normal rate; the activity of Kalirin was entirely dependent on the activity
      of the first GEF domain. KalGEF1-induced sprouting of new fibers from
      lamellipodial structures was accompanied by extensive actin cytoskeleton
      reorganization. The kalGEF1 phenotype was mimicked by constitutively active RhoG
      and was blocked by RhoG inhibitors. Constitutively active Rac1, RhoA, and Cdc42
      were unable to initiate new axons, whereas dominant-negative Rac1, RhoA, and
      Cdc42 failed to block axon sprouting. Thus Kalirin, acting via RhoG in a novel
      manner, plays a central role in establishing the morphological phenotypic
      diversity that is essential to the connectivity of the developing nervous system.

PMID- 12177197
TI  - Signaling of layer 1 and whisker-evoked Ca2+ and Na+ action potentials in distal
      and terminal dendrites of rat neocortical pyramidal neurons in vitro and in vivo.
AB  - Dendritic regenerative potentials play an important role in integrating and
      amplifying synaptic inputs. To understand how distal synaptic inputs are
      integrated and amplified, we made multiple simultaneous (double, triple, or
      quadruple) and sequential (4-12 paired) recordings from different locations of
      single tufted layer 5 pyramidal neurons in the cortex in vitro and studied the
      spatial and temporal properties of their dendritic regenerative potential initial
      zone. Recordings from the soma and from trunk, primary, secondary, tertiary, and
      quaternary tuft branches of the apical dendrite of these neurons reveal a
      spatially restricted low-threshold zone approximately 550-900 microm from the
      soma for Ca2+-dependent regenerative potentials. Dendritic regenerative
      potentials initiated in this zone have a clearly defined threshold and a
      refractory period, and they can propagate actively along the dendrite before
      evoking somatic action potentials. The detailed biophysical characterization of
      this dendritic action potential initiation zone allowed for the further
      investigation of dendritic potentials in the intact brain and their roles in
      information processing. By making whole-cell recordings from the soma and varied
      locations along the apical dendrite of 53 morphologically identified layer 5
      pyramidal neurons in anesthetized rats, we found that three of the dendritic
      potentials characterized in vitro could be induced by spontaneous or whisker
      inputs in vivo. Thus layer 5 pyramidal neurons of the rat neocortex have a
      spatially restricted low-threshold zone in the apical dendrite, the activation or
      interaction of which with the axonal action potential initiation zone is
      responsible for multiple forms of regenerative potentials critical for
      integrating and amplifying sensory and modulatory inputs.

PMID- 12177198
TI  - An in vitro model of Parkinson's disease: linking mitochondrial impairment to
      altered alpha-synuclein metabolism and oxidative damage.
AB  - Chronic systemic complex I inhibition caused by rotenone exposure induces
      features of Parkinson's disease (PD) in rats, including selective nigrostriatal
      dopaminergic degeneration and formation of ubiquitin- and alpha-synuclein
      positive inclusions (Betarbet et al., 2000). To determine underlying mechanisms
      of rotenone-induced cell death, we developed a chronic in vitro model based on
      treating human neuroblastoma cells with 5 nm rotenone for 1-4 weeks. For up to 4
      weeks, cells grown in the presence of rotenone had normal morphology and growth
      kinetics, but at this time point, approximately 5% of cells began to undergo
      apoptosis. Short-term rotenone treatment (1 week) elevated soluble alpha
      synuclein protein levels without changing message levels, suggesting that alpha
      synuclein degradation was retarded. Chronic rotenone exposure (4 weeks) increased
      levels of SDS-insoluble alpha-synuclein and ubiquitin. After a latency of >2
      weeks, rotenone-treated cells showed evidence of oxidative stress, including loss
      of glutathione and increased oxidative DNA and protein damage. Chronic rotenone
      treatment (4 weeks) caused a slight elevation in basal apoptosis and markedly
      sensitized cells to further oxidative challenge. In response to H2O2, there was
      cytochrome c release from mitochondria, caspase-3 activation, and apoptosis, all
      of which occurred earlier and to a much greater extent in rotenone-treated cells;
      caspase inhibition provided substantial protection. These studies indicate that
      chronic low-grade complex I inhibition caused by rotenone exposure induces
      accumulation and aggregation of alpha-synuclein and ubiquitin, progressive
      oxidative damage, and caspase-dependent death, mechanisms that may be central to
      PD pathogenesis.

PMID- 12177199
TI  - Spatial and temporal regulation of Ca2+/calmodulin-dependent protein kinase II
      activity in developing neurons.
AB  - We have studied Ca2+/calmodulin-dependent protein kinase II (CaMKII) isoform
      distribution and activity in embryonic hippocampal neurons developing in culture.
      We have found a strong correlation between the expression of the alpha subunit of
      the enzyme and the ability to undergo depolarization-dependent phosphorylation,
      which in young neurons is limited to the somatodendritic pool of the kinase. The
      lack of responsiveness of the axons of young alphaCaMKII-positive neurons is not
      caused by a lower Ca2+ influx but rather by a differential balance between kinase
      and phosphatase activities in this compartment. After the establishment of
      synaptic contacts, the presynaptic pool of the kinase displays an increasing
      level of activity and acquires the parallel ability to phosphorylate synapsin I,
      which represents one of the major CaMKII presynaptic targets in mature nerve
      terminals. In contrast, the activity of the postsynaptic pool of the kinase
      remains constant throughout synaptogenesis. In the presence of a nearly
      homogeneous subcellular distribution, this highly regionalized regulation of
      activity may reflect the multifunctional roles of CaMKII in both developing and
      mature neurons.

PMID- 12177200
TI  - Regulation of A-kinase anchoring protein 79/150-cAMP-dependent protein kinase
      postsynaptic targeting by NMDA receptor activation of calcineurin and remodeling
      of dendritic actin.
AB  - At the postsynaptic membrane of glutamatergic synapses, the cAMP-dependent
      protein kinase (PKA), protein kinase C (PKC), and calcineurin (CaN) anchoring
      protein AKAP79/150 is recruited to NMDA and AMPA glutamate receptors by
      postsynaptic density (PSD)-95 family membrane-associated guanylate kinase (MAGUK)
      scaffold proteins. These signaling scaffold complexes may function to regulate
      receptor phosphorylation in synaptic plasticity. Thus, it is important to
      understand regulation of AKAP79/150 targeting to synapses and recruitment to PSD
      MAGUK complexes. AKAP79 is targeted to the plasma membrane by an N-terminal basic
      domain that binds phosphatidylinositol-4,5-bisphosphate (PI-4,5-P(2)) and is
      regulated by PKC phosphorylation and calmodulin binding. Here we demonstrate that
      this same domain also binds F-actin in a calmodulin- and PKC-regulated manner,
      targets to membrane ruffles enriched in F-actin and PI-4,5-P(2) in COS7 cells,
      and localizes to dendritic spines with F-actin and PSD-MAGUKs in hippocampal
      neurons. Inhibition of actin polymerization disrupted AKAP79 targeting of PKA and
      CaN to ruffles in COS7 cells and endogenous AKAP79/150 dendritic spine
      localization with PKA, CaN, and PSD-MAGUKs in neurons. AKAP79/150 postsynaptic
      localization was rapidly regulated by NMDA receptors through CaN activation and F
      actin remodeling, further suggesting that AKAP79/150 signaling scaffold targeting
      depends on actin dynamics. NMDA receptor activation also regulated dendritic
      spine localization of PKA and CaN and association of the AKAP79/150-PKA complex
      with PSD-MAGUKs. Because AMPA receptor PKA phosphorylation and synaptic
      localization are regulated by similar NMDA receptor-CaN signaling pathways linked
      to hippocampal long-term depression, this regulation of AKAP79/150 postsynaptic
      targeting might be important for synaptic plasticity.

PMID- 12177201
TI  - The multiple LIM domain-containing adaptor protein Hic-5 synaptically colocalizes
      and interacts with the dopamine transporter.
AB  - The Na+/Cl--dependent dopamine transporter (DAT) is critical in terminating
      dopaminergic transmission by removing the transmitter away from the synapse.
      Several lines of evidence suggest that transporter-interacting proteins may play
      a role in DAT function and regulation. In this report, using the yeast two-hybrid
      system, we have identified a novel interaction between DAT and the multiple Lin
      11, Isl-1, and Mec-3 (LIM) domain-containing adaptor protein Hic-5. This
      association involves the N-terminal portion of the intracellular tail of DAT and
      the LIM region of Hic-5. In human embryonic kidney 293 cells, Hic-5 colocalizes
      with DAT at polarized sites and reduces DAT uptake activity through a mechanism
      involving a decrease in the cell-surface levels of the transporter. A fragment of
      Hic-5 containing the LIM domains is sufficient to bind DAT but lacks the ability
      to inhibit transporter activity. In addition, the LIM fragment prevents the
      effect of the full-length Hic-5 on DAT localization and function. In the brain,
      Hic-5 protein is expressed in the cerebral cortex, hippocampus, hypothalamus,
      cerebellum, and striatum, suggesting a role for this protein in the nervous
      system. The association of the endogenous Hic-5 and DAT proteins was confirmed
      biochemically by coimmunoprecipitation from brain striatal extracts. Moreover,
      immunostaining of rat midbrain neurons in culture revealed a presynaptic
      colocalization of Hic-5 and DAT. Because Hic-5 has been shown to interact with
      several signaling molecules, including the nonreceptor protein tyrosine kinases
      focal adhesion kinase and Fyn, this raises the possibility that this adaptor
      protein may link DAT to intracellular signaling pathways.

PMID- 12177202
TI  - In vivo labeling of parvalbumin-positive interneurons and analysis of electrical
      coupling in identified neurons.
AB  - GABAergic interneurons can pace the activity of principal cells and are thus
      critically involved in the generation of oscillatory and synchronous network
      activity. The specific role of various GABAergic subpopulations, however, has
      remained elusive. This is in part attributable to the scarcity of certain
      GABAergic neurons and the difficulty of identifying them in slices obtained from
      brain regions in which anatomical structures are not readily recognizable in the
      live preparation. To facilitate the functional analysis of GABAergic
      interneurons, we generated transgenic mice in which the enhanced green
      fluorescent protein (EGFP) was specifically expressed in parvalbumin-positive
      neurons. The high fidelity of expression obtained using bacterial artificial
      chromosome transgenes resulted in EGFP-labeled neurons in nearly all brain
      regions known to contain parvalbumin-expressing neurons. Immunocytochemical
      analysis showed that EGFP expression was primarily restricted to parvalbumin
      positive cells. In addition to cell body labeling, EGFP expression was high
      enough in many neurons to enable the visualization of dendritic structures. With
      the help of these mice, we investigated the presence of electrical coupling
      between parvalbumin-positive cells in brain slices obtained from young and adult
      animals. In dentate gyrus basket cells, electrical coupling was found in slices
      from young [postnatal day 14 (P14)] and adult (P28 and P42) animals, but both
      strength and incidence of coupling decreased during development. However,
      electrical coupling between parvalbumin-positive multipolar cells in layer II/III
      of the neocortex remains unaltered during development. Yet another developmental
      profile of electrical coupling was found between layer II/III parvalbumin
      positive cells and excitatory principal cells. Between these neurons, electrical
      coupling was found at P14 but not at P28. The results indicate that the presence
      and strength of electrical coupling is developmentally regulated with respect to
      brain area and cell type.

PMID- 12177203
TI  - Regulation of structural plasticity by different channel types in rod and cone
      photoreceptors.
AB  - In response to retinal disease and injury, the axon terminals of rod
      photoreceptors demonstrate dramatic structural plasticity, including axonal
      retraction, neurite extension, and the development of presynaptic varicosities.
      Cone cell terminals, however, are relatively inactive. Similar events are
      observed in primary cultures of salamander photoreceptors. To investigate the
      mechanisms underlying these disparate presynaptic responses, antagonists to
      voltage-gated L-type and cGMP-gated channels, known to be present on rod and cone
      cell terminals, respectively, were used to block calcium influx during critical
      periods of plasticity in vitro. In rod cells, L-type channel antagonists
      nicardipine and verapamil inhibited not only the outgrowth of processes and the
      formation of varicosities, but also the synthesis of vesicle proteins, SV2 and
      synaptophysin. In contrast, the synthesis of opsin in rod cells was unaffected.
      In cone cells, L-type channel antagonists caused only modest changes. However,
      cobalt bromide, which blocks all calcium channels, and l-cis-diltiazem, a potent
      antagonist of cGMP-gated channels, significantly inhibited varicosity formation
      and synthesis of SV2 in cone cells. Moreover, the cGMP-gated channel agonist 8
      bromo-cGMP caused a significant increase in varicosity formation by cone but not
      rod cells. Thus voltage-gated L-type channels in rod cells and cGMP-gated
      channels in cone cells are the primary calcium channels required for structural
      plasticity and the accompanying upregulation of synaptic vesicle synthesis. The
      differing responses of rod and cone terminals to injury and disease may be
      determined by these differences in the regulation of Ca2+ influx.

PMID- 12177204
TI  - Identification of domains of netrin UNC-6 that mediate attractive and repulsive
      guidance and responses from cells and growth cones.
AB  - Netrin UNC-6 is a protein secreted from ventral cells that guides cell and growth
      cone migrations in Caenorhabditis elegans. Previously it was shown that UNC-6
      domain V-2 regulates dorsal guidance activity and domain C regulates an activity
      that prevents the branching of axons when they respond to the N-terminal domains.
      Because these results indicate that the biological activities of UNC-6 are
      mediated through specific domains, we systematically examined each UNC-6 domain
      for guidance activities. Transgenic animals expressing UNC-6 derivatives with
      domain deletions and mutants with selective unc-6 loss-of-function mutations were
      analyzed. The results indicate that the VI, V-2, and V-3 domains are primarily
      required for dorsal migrations and the VI and V-3 domains are required for
      ventral migrations. These domains are likely important for responses mediated by
      the UNC-5 and UNC-40 receptors, respectively. Deletion of V-3 and a V-3 point
      mutation selectively affect either cell or growth cone migrations, indicating
      that each migration requires unique interactions with UNC-6. Deletion of domain
      VI or of a conserved eight amino acid motif within VI causes loss of all UNC-6
      guidance activities, and mutations within domain VI selectively affect different
      guidance activities, suggesting that domain VI regulates each response to UNC-6.
      We propose that individual UNC-6 domains mediate different signals, which act in
      parallel to regulate the morphological changes necessary for guidance.

PMID- 12177205
TI  - Gap junction proteins expressed during development are required for adult neural
      function in the Drosophila optic lamina.
AB  - We provide evidence that gap junction proteins, expressed during development, are
      necessary for the formation of normally functioning connections in the Drosophila
      optic lamina. Flies with mutations in the gap junction genes (innexins),
      shakingB, and ogre have normal photoreceptor potentials but a defective response
      of the postsynaptic cells in the optic lamina. This is indicated by a reduction
      in, or absence of, transients in the electroretinogram. Ogre is required in the
      presynaptic retinal photoreceptors. ShakingB(N) is, at a minimum, required in
      postsynaptic lamina neurons. Transgenic expression of the appropriate innexins
      during pupal development (but not later) rescues connection defects. Transient
      gap junctions have been observed to precede chemical synapse formation and have
      been hypothesized to play a role in connectivity and synaptogenesis; however, no
      causal role has been demonstrated. Here we show that developmental gap junction
      genes can be required for normally functioning neural connections to form.

PMID- 12177206
TI  - Long-lasting sprouting and gene expression changes induced by the monoclonal
      antibody IN-1 in the adult spinal cord.
AB  - Lesion-induced plasticity of the rat corticospinal tract (CST) decreases
      postnatally, simultaneously with myelin appearance. In adult rats, compensatory
      sprouting can be induced by the monoclonal antibody (mAb) IN-1 raised against the
      growth inhibitory protein Nogo-A. In this study, we examined separately the fate
      of sensory and motor corticospinal fibers after mAb IN-1 application. Intact
      adult rats treated with the IN-1 antibody exhibited an increase of aberrant CST
      projections, i.e., sensory fibers projecting into the ventral horn and motor
      fibers projecting dorsally. Unilateral lesion of the CST [pyramidotomy (PTX)] in
      the presence of mAb IN-1 triggered a progressive reorganization of the sprouting
      of the remaining CST across the midline, with sensory fibers projecting gradually
      into the denervated dorsal horn and motor fibers projecting into the denervated
      ventral horn. In unilaterally denervated spinal cords, aberrant sprouts were only
      transient and disappeared by 6 weeks, whereas midline crossing fibers ending in
      the appropriate target region were stabilized and persisted over the entire study
      period. Within the spinal cord, IN-1 antibody treatment was associated with
      upregulation of growth factors (BDNF, VEGF), growth-related proteins (actin,
      myosin, GAP-43), and transcription factors (STATs), whereas pyramidotomy induced
      an enhanced expression of guidance molecules (semaphorins and slits) as well as
      neurotrophic factors (BDNF, IGFs, BMPs). These gene expression changes may
      contribute to attraction, guidance, and stabilization of sprouting CST fibers.

PMID- 12177207
TI  - Ensheathing cells and methylprednisolone promote axonal regeneration and
      functional recovery in the lesioned adult rat spinal cord.
AB  - Axons fail to regenerate after spinal cord injury (SCI) in adult mammals, leading
      to permanent loss of function. After SCI, ensheathing cells (ECs) promote
      recovery in animal models, whereas methylprednisolone (MP) promotes neurological
      recovery in humans. In this study, the effectiveness of combining ECs and MP
      after SCI was investigated for the first time. After lesioning the corticospinal
      tract in adult rats, ECs were transplanted into the lesion, and MP was
      administered for 24 hr. At 6 weeks after injury, functional recovery was assessed
      by measuring successful performance of directed forepaw reaching (DFR), expressed
      as percentages. Axonal regeneration was analyzed by counting the number of
      corticospinal axons, anterogradely labeled with biotin dextran
      tetramethylrhodamine, caudal to the lesion. Lesioned control rats, receiving
      either no treatment or vehicle, had abortive axonal regrowth (1 mm) and poor DFR
      success (38 and 42%, respectively). Compared with controls, MP-treated rats had
      significantly more axons 7 mm caudal to the lesion, and DFR performance was
      significantly improved (57%). Rats that received ECs in combination with MP had
      significantly more axons than all other lesioned rats up to 13 mm. Successful DFR
      performance was significantly higher in rats with EC transplants, both without
      (72%) and with (78%) MP, compared with other lesioned rats. These data confirm
      previous reports that ECs promote axonal regeneration and functional recovery
      after spinal cord lesions. In addition, this research provides evidence that,
      when used in combination, MP and ECs improve axonal regrowth up to 13 mm caudal
      to the lesion at 6 weeks after injury.

PMID- 12177208
TI  - Transplantation of olfactory mucosa minimizes axonal branching and promotes the
      recovery of vibrissae motor performance after facial nerve repair in rats.
AB  - The occurrence of abnormally associated movements is inevitable after facial
      nerve transection. The reason for this post-paralytic syndrome is poor guidance
      of regrowing axons, whereby a given muscle group is reinnervated by misrouted
      axonal branches. Olfactory ensheathing glia have been shown to reduce axonal
      sprouting and stimulate axonal regeneration after transplantation into the spinal
      cord. In the present study, we asked whether transplantation of olfactory mucosa
      (OM) would also reduce sprouting of a damaged peripheral pure motor nerve. The
      adult facial nerve was transected, and the effect of the OM placed at the lesion
      site was analyzed with regard to the accuracy of target reinnervation, axonal
      sprouting of motoneurons, and vibrissal motor performance. Accuracy of target
      reinnervation and axonal sprouting were studied using preoperative/postoperative
      labeling and triple retrograde labeling of facial motoneurons, respectively. The
      vibrissal motor performance was monitored using a video-based motion analysis. We
      show here that implantation of OM, compared with simple facial-facial
      anastomosis, (1) improved the protraction, amplitude, angular velocity, and
      acceleration of vibrissal movements up to 80% of the control values, (2) reduced
      the percentage of branching motoneurons from 76 to 39%, and (3) improved the
      accuracy of reinnervation from 22 to 49%. Moreover, we present evidence, that
      transplanted OM but not buccal mucous membrane induced a sustained upregulation
      of trophic factors at the lesion site. It is concluded that transplantation of OM
      to the transected facial nerve significantly improves nerve regeneration.

PMID- 12177209
TI  - Specification of cerebellar progenitors after heterotopic-heterochronic
      transplantation to the embryonic CNS in vivo and in vitro.
AB  - The different cerebellar phenotypes are generated according to a precise time
      schedule during embryonic and postnatal development. To assess whether the
      differentiative potential of cerebellar progenitors is progressively restricted
      in space and time we examined the fate of embryonic day 12 (E12) or postnatal day
      4 (P4) cerebellar cells after heterotopic-heterochronic transplantation into the
      embryonic rat brain in utero or into organotypic CNS explants in vitro. Donor
      cells, isolated from transgenic mice overexpressing the enhanced-green
      fluorescent protein under the control of the beta-actin-promoter, engrafted
      throughout the host brainstem and diencephalon, whereas they rarely incorporated
      into specific telencephalic structures. In any recipient site, the vast majority
      of transplanted cells could be recognized as cerebellar phenotypes, and we did
      not obtain clear evidence that ectopically located cells adopted host-specific
      identities. Nevertheless, the two donor populations displayed different
      developmental potentialities. P4 progenitors exclusively generated granule cells
      and molecular layer interneurons, indicating that they are committed to late
      generated cerebellar identities and not responsive to heterotopic-heterochronic
      environmental cues. In contrast, E12 precursors had the potential to produce all
      major cerebellar neurons, but the repertoire of adult phenotypes generated by
      these cells was different in distinct host regions, suggesting that they require
      instructive environmental information to acquire mature identities. Thus,
      cerebellar precursors are able to integrate into different foreign brain regions,
      where they develop mature phenotypes that survive long after transplantation, but
      they are committed to cerebellar fates at E12. Embryonic progenitors are
      initially capable, although likely not competent, to generate all cerebellar
      identities, but their potential is gradually restricted toward late-generated
      phenotypes.

PMID- 12177210
TI  - Contrasting effects of WIN 55212-2 on motility of the rat bladder and uterus.
AB  - Both the uterus and bladder contain cannabinoid (CB) receptors whose functions
      are poorly understood. Here, in urethane-anesthetized female rats in metestrus,
      we simultaneously compared the effects of close-arterial injections of the
      cannabinoid receptor agonist WIN 55,212-2 (WIN2) on uterine contractions
      (amplitude and rate) and micturition thresholds (MT) assessed by cystometry. Five
      doses of WIN2 were delivered (0.01, 0.1, 0.5, 1, and 1.5 micromol/kg) in three
      groups: (1) controls; (2) after bladder inflammation with intravesicular
      turpentine; and (3) after bilateral hypogastric neurectomy (HYPX). In some rats,
      drugs were delivered via the tail vein. Regarding bladder, WIN2 dose-dependently
      reduced MTs in all groups. Both bladder inflammation and HYPX significantly
      increased this effect. Regarding uterus, WIN2 dose-dependently increased uterine
      contraction amplitude. Bladder inflammation or HYPX significantly decreased this
      effect. Coinjection of the CB1 antagonist SR141716A (SR) (1.5 micromol/kg) and
      WIN2 (0.5 micromol/kg) abolished or reduced the effects of WIN2 in both organs.
      SR alone had significant effects only after HYPX, reducing both MT and uterine
      contraction amplitude. The vehicle (0.4% DMSO) and inactive enantiomer S(-)-WIN
      55,212-3 were both ineffective. Close-arterial injections of WIN2 (0.5
      micromol/kg) produced significantly larger effects in both organs than tail vein
      injections. These results indicate that, whereas WIN2 reduces bladder motility,
      it mainly increases uterine motility, likely via CB1 receptors located in the two
      organs. The opposing effects of bladder inflammation and HYPX on the potency of
      WIN in the two organs suggest a neurally mediated viscero-visceral interaction in
      which bladder inflammation influences uterine CB1 sensitivity, possibly by
      inhibiting adrenergic input to the uterus.

PMID- 12177211
TI  - The neural cell adhesion molecule regulates cell-surface delivery of G-protein
      activated inwardly rectifying potassium channels via lipid rafts.
AB  - Mice deficient in the neural cell adhesion molecule (NCAM) exhibit increased
      anxiety and anxiolytic sensitivity to serotonin 5-HT1A receptor agonists. Here,
      we investigate the relationship between NCAM and 5-HT1A receptor signaling
      pathways modulating G-protein-activated inwardly rectifying K+ (Kir3) channels.
      When studying this relationship in cultured hippocampal neurons, we observed that
      in cells from NCAM-deficient mice, inwardly rectifying K+ (Kir3) currents were
      increased compared with wild-type controls. Analysis of this modulatory mechanism
      in Xenopus oocytes and Chinese hamster ovary (CHO) cells revealed that the
      recombinantly expressed major transmembrane isoforms NCAM140 and NCAM180
      specifically reduced inward currents generated by neuronal Kir3.1/3.2 and
      Kir3.1/3.3 but not by cardiac Kir3.1/3.4 channels. Using fluorescence
      measurements and surface biotinylation assays, we show that this effect was
      caused by a reduced surface localization of Kir3 channels. Furthermore,
      expression of flag-tagged Kir3 channels in cultured neurons of NCAM-deficient
      mice resulted in a higher transport of these channels into neurites and a higher
      cell-surface localization compared with wild-type neurons. Neuronal Kir3 channels
      and NCAM isoforms are associated with cholesterol-rich microdomains (lipid rafts)
      in CHO cells and in isolated brain membranes. Mutational and pharmacological
      disruption of the lipid raft association of NCAM140 normalizes surface delivery
      of channels. We conclude that the transmembrane isoforms of NCAM reduce the
      transport of Kir3 channels to the cell surface via lipid rafts. Thus, regulation
      of Kir3 channel activity by NCAM may represent a novel mechanism controlling long
      term excitability of neurons.

PMID- 12177212
TI  - Functional synaptic projections onto subplate neurons in neonatal rat
      somatosensory cortex.
AB  - Subplate neurons (SPn) play an important role in the formation of thalamocortical
      connections during early development and show glutamatergic and GABAergic
      spontaneous synaptic activity. We characterized these synaptic inputs by
      performing whole-cell recordings from SPn in somatosensory cortical slices of
      postnatal day 0-3 rats. At -70 mV, electrical stimulation of the thalamocortical
      afferents elicited in 68% of the SPn a monosynaptic CNQX-sensitive postsynaptic
      current (PSC). These fast PSCs were mediated by AMPA receptors, because they were
      prolonged by cyclothiazide and blocked by GYKI 52466. On membrane depolarization,
      thalamocortical stimulation elicited in 50% of the cells an additional slow
      monosynaptic component mediated by NMDA receptors. Stimulation of the cortical
      plate evoked in 72% of SPn a monosynaptic AMPA receptor-mediated PSC with an
      additional NMDA component at depolarized membrane potentials and in 40% of the
      investigated cells polysynaptic responses, depending on GABA(A) and NMDA
      receptors. Stimulation of the subplate elicited in 67% of SPn a monosynaptic dual
      component PSC mediated by AMPA and NMDA receptors activated at -70 mV and in 12%
      of SPn a monosynaptic single-component PSC mediated by AMPA receptors with an
      additional NMDA component activated at depolarized membrane potentials. A
      monosynaptic GABAergic response could be observed in 68% of SPn after stimulation
      of the subplate. In gramicidin-perforated patch recordings, bath application of
      GABA caused membrane depolarization to -40 mV and elicited action potentials.
      These results demonstrate that SPn receive distinct functional synaptic inputs
      arising from the thalamus, cortical plate, and subplate, indicating that SPn are
      capable of integrating and processing information from cortical and subcortical
      regions.

PMID- 12177213
TI  - Impairment of L-type Ca2+ channel-dependent forms of hippocampal synaptic
      plasticity in mice deficient in the extracellular matrix glycoprotein tenascin-C.
AB  - The extracellular matrix glycoprotein tenascin-C (TN-C) has been suggested to
      play important functional roles during neural development, axonal regeneration,
      and synaptic plasticity. We generated a constitutively TN-C-deficient mouse
      mutant from embryonic stem cells with a floxed tn-C allele, representing a
      standard for future analysis of conditionally targeted mice. The gross morphology
      of the CNS was not detectably affected, including no evidence for perturbed nerve
      cell migration, abnormal oligodendrocyte distribution, or defective myelination.
      Despite the apparent normal histology of the hippocampus and normal performance
      in the water maze, theta-burst stimulation (TBS) of Schaffer collaterals elicited
      reduced long-term potentiation (LTP) in the CA1 region of TN-C-deficient mutants,
      as compared with wild-type littermates. However, high-frequency stimulation
      evoked normal LTP not only in CA1, but also at mossy fiber-CA3 and medial and
      lateral perforant path-granule cell synapses in the dentate gyrus. Low-frequency
      stimulation failed to induce long-term depression in the CA1 region of TN-C
      deficient animals. Recordings of TBS-induced LTP in the presence of nifedipine,
      an antagonist of L-type voltage-dependent Ca2+ channels (VDCCs), did not affect
      LTP in TN-C-deficient mice, but reduced LTP in wild-type mice to the levels seen
      in mutants. Furthermore, chemical induction of a L-type VDCC-dependent LTP in the
      CA1 region by application of the K+ channel blocker tetraethylammonium resulted
      in impaired LTP in TN-C mutants. Thus, reduction in L-type VDCC-mediated
      signaling appears to mediate the deficits in certain forms of synaptic plasticity
      in constitutively TN-C-deficient mice.

PMID- 12177214
TI  - Retinotopy and functional subdivision of human areas MT and MST.
AB  - We performed a series of functional magnetic resonance imaging experiments to
      divide the human MT+ complex into subregions that may be identified as homologs
      to a pair of macaque motion-responsive visual areas: the middle temporal area
      (MT) and the medial superior temporal area (MST). Using stimuli designed to tease
      apart differences in retinotopic organization and receptive field size, we
      established a double dissociation between two distinct MT+ subregions in 8 of the
      10 hemispheres studied. The first subregion exhibited retinotopic organization
      but did not respond to peripheral ipsilateral stimulation, indicative of smaller
      receptive fields. Conversely, the second subregion within MT+ did not demonstrate
      retinotopic organization but did respond to peripheral stimuli in both the
      ipsilateral and contralateral visual hemifields, indicative of larger receptive
      fields. We tentatively identify these subregions as the human homologues of
      macaque MT and MST, respectively. Putative human MT and MST were typically
      located on the posterior/ventral and anterior/dorsal banks of a dorsal/posterior
      limb of the inferior temporal sulcus, similar to their relative positions in the
      macaque superior temporal sulcus.

PMID- 12177215
TI  - Genetic influence on quantitative features of neocortical architecture.
AB  - The layout of functional cortical maps exhibits a high degree of interindividual
      variability that may account for individual differences in sensory and cognitive
      abilities. By quantitatively assessing the interindividual variability of
      orientation preference columns in the primary visual cortex, we demonstrate that
      column sizes and shapes as well as a measure of the homogeneity of column sizes
      across the visual cortex are significantly clustered in genetically related
      animals and in the two hemispheres of individual brains. Taking the developmental
      timetable of column formation into account, our data indicate a substantial
      genetic influence on the developmental specification of visual cortical
      architecture and suggest ways in which genetic information may influence an
      individual's visual abilities.

PMID- 12177216
TI  - Compromised hemodynamic response in amyloid precursor protein transgenic mice.
AB  - APP23 transgenic mice overexpressing amyloid precursor protein (APP751) reproduce
      neuropathological changes associated with Alzheimer's disease such as high levels
      of amyloid plaques, cerebral amyloid angiopathy, and associated vascular
      pathologies. Functional magnetic resonance imaging (fMRI) was applied to
      characterize brain functionality in these mice through global pharmacological
      stimulation. The cerebral hemodynamic response to infusion of the GABA(A)
      antagonist bicuculline was significantly reduced in aged APP23 mice compared with
      age-matched wild-type littermates. This is in part attributable to a compromised
      cerebrovascular reactivity, as revealed by the reduced responsiveness to
      vasodilatory stimulation by acetazolamide. The study shows that fMRI is a
      sensitive tool to phenotype genetically engineered animals modeling
      neuropathologies.

PMID- 12177217
TI  - Rewarding and psychomotor stimulant effects of endomorphin-1: anteroposterior
      differences within the ventral tegmental area and lack of effect in nucleus
      accumbens.
AB  - Endomorphin-1 (EM-1) is a recently isolated endogenous peptide having potent
      analgesic activity and high affinity and selectivity for the mu-opioid receptor.
      The present study was designed to investigate the rewarding and psychomotor
      stimulant effects of EM-1 in specific brain regions. We found that rats would
      learn without priming or response shaping to lever-press for microinjections of
      EM-1 into the ventral tegmental area (VTA); responding was most vigorous for high
      dose injections into the posterior VTA. Rats did not learn to lever-press for
      microinjections of EM-1 into the nucleus accumbens (NAS) or regions just dorsal
      to the VTA. Lever-pressing for EM-1 in the VTA was extinguished when vehicle was
      substituted for the peptide and was reinstated when EM-1 reinforcement was re
      established. Conditioned place preference was established by EM-1 injections into
      the posterior but not the anterior VTA or the NAS. Injection of EM-1 (0.1-1.0
      nmol) into the posterior VTA induced robust increases in locomotor activity,
      whereas injections into the anterior VTA had very weak locomotor-stimulating
      effects. When injected into the NAS, EM-1 (0.1-10.0 nmol) did not affect
      locomotor activity. The present findings implicate the posterior VTA as a highly
      specific and sensitive site for opioid reward and suggest a role for EM-1
      containing projections to the posterior VTA in the rewarding effects of other
      reinforcers.

PMID- 12177218
TI  - Age-related enhancement of the slow outward calcium-activated potassium current
      in hippocampal CA1 pyramidal neurons in vitro.
AB  - Aging is associated with learning deficits and a decrease in neuronal
      excitability, reflected by an enhanced post-burst afterhyperpolarization (AHP),
      in CA1 hippocampal pyramidal neurons. To identify the current(s) underlying the
      AHP altered in aging neurons, whole-cell voltage-clamp recording experiments were
      performed in hippocampal slices from young and aging rabbits. Similar to previous
      reports, aging neurons were found to rest at more hyperpolarized potentials and
      have larger AHPs than young neurons. Given that compounds that reduce the slow
      outward calcium-activated potassium current (sI(AHP)), a major constituent of the
      AHP, also facilitate learning in aging animals, the sI(AHP) was pharmacologically
      isolated and characterized. Aging neurons were found to have an enhanced sI(AHP,)
      the amplitude of which was significantly correlated to the amplitude of the AHP
      (r = 0.63; p < 0.001). Thus, an enhanced sI(AHP) contributes to the enhanced AHP
      in aging. No differences were found in the membrane resistance, capacitance, or
      kinetic and voltage-dependent properties of the sI(AHP). Because enhanced AHP in
      aging neurons has been hypothesized to be secondary to an enhanced Ca2+ influx
      via the voltage-gated L-type Ca2+ channels, we further examined the sI(AHP) in
      the presence of an L-type Ca2+ channel blocker, nimodipine (10 microm).
      Nimodipine caused quantitatively greater reductions in the sI(AHP) in aging
      neurons than in young neurons; however, the residual sI(AHP) was still
      significantly larger in aging neurons than in young neurons. Our data, in
      conjunction with previous studies showing a correlation between the AHP and
      learning, suggest that the enhancement of the sI(AHP) in aging is a mechanism
      that contributes to age-related learning deficits.

PMID- 12177219
TI  - Altered discharge pattern of basal ganglia output neurons in an animal model of
      idiopathic dystonia.
AB  - A decreased activity of basal ganglia output neurons is thought to underlie
      idiopathic dystonias and other hyperkinetic movement disorders. We found recently
      a reduced spontaneous discharge rate of entopeduncular neurons (internal globus
      pallidus in primates) in dt(sz) hamsters, an unique model for idiopathic
      paroxysmal dystonia in which stress-inducible attacks show an age-dependent
      severity. Otherwise, it has been suggested that an altered discharge pattern may
      be more important for the occurrence of dystonia than a reduced discharge rate.
      Based on qualitative and computerized quantitative evaluations of interspike
      interval histograms and spike trains of extracellularly recorded single neurons,
      we investigated the spontaneous discharge pattern of GABAergic entopeduncular and
      nigral neurons in dt(sz) hamsters at different ages. The discharge pattern of
      entopeduncular neurons was highly irregular and showed an altered burst-like
      firing in dt(sz) hamsters at the age of the most marked expression of dystonia
      when compared with age-matched nondystonic controls. In line with a recently
      reported normalization of discharge rates after age-dependent disappearance of
      dystonia, we found an almost complete normalization of the discharge pattern of
      entopeduncular neurons after remission of dystonia in dt(sz) hamsters.
      Investigations of GABAergic nigral neurons, reported recently to have the same
      spontaneous discharge rates in dystonic and nondystonic hamsters, did not show an
      altered firing pattern in dt(sz) hamsters. The present data clearly indicate the
      fundamental importance of an altered discharge pattern of entopeduncular neurons
      for the expression of paroxysmal dystonia, and probably also for other
      dyskinesias, and may explain the improvements obtained by pallidotomy in dystonic
      patients despite an obviously reduced pallidal output.

PMID- 12177220
TI  - Physiology of the auditory afferents in an acoustic parasitoid fly.
AB  - The fly, Ormia ochracea, possess a novel auditory organ, which allows it to
      detect airborne sounds. The mechanical coupling of its pair of tympanal membranes
      provides the basis for a unique means of sensing the direction of a sound source.
      In this study, we characterized the neuroanatomy, frequency tuning, and
      neurophysiological response properties of the acoustic afferents. Our experiments
      demonstrate that the fly's nervous system is able to encode and localize the
      direction of a sound source, although the binaural auditory cues available in the
      acoustic sound field are miniscule. Almost all of the acoustic afferents recorded
      in this study responded to short and long sound pulses with a phasic burst of one
      to four action potentials. A few afferents responded tonically for the duration
      of the sound stimulus. A prominent class of afferents responds to suprathreshold
      stimuli with only a single spike discharge, independent of stimulus level,
      frequency, or duration. We also tested the response of the afferents to speakers
      separated by 180 degrees along the azimuth of the fly. We found that the afferent
      responses have a shorter latency because of ipsilateral stimulation. This could
      be a temporal code of the direction of a sound source. The threshold frequency
      tuning for the afferents revealed a range of sensitivities to the frequency of
      the cricket host's calling song frequency. The difference in the number of
      afferents above threshold on either side of the animal is a population code,
      which can also be used for sound localization.

PMID- 12177221
TI  - Exposure of adolescent rats to oral methylphenidate: preferential effects on
      extracellular norepinephrine and absence of sensitization and cross-sensitization
      to methamphetamine.
AB  - Methylphenidate (MP) (ritalin) is widely used in the treatment of children and
      adolescents with attention deficit hyperactivity disorder, but little is known
      about therapeutic mechanisms or about possible consequences of long-term
      exposure. To more closely simulate the clinical use of the drug, we orally
      administered MP to adolescent rats during the dark-active phase of the circadian
      cycle at doses (0.75-3.0 mg/kg) below threshold for locomotor activation. We
      found that doses in this range increased extracellular norepinephrine in
      hippocampus without affecting dopamine in nucleus accumbens. These results
      suggest that norepinephrine systems may play an important role in the therapeutic
      action of this drug. To examine one potential consequence of long-term exposure
      to MP, i.e., the development of locomotor sensitization, an adaptational change
      that has been implicated in drug abuse liability, animals received three daily
      oral administrations of these doses of MP for up to 4 weeks through adolescence.
      The animals were then challenged with methamphetamine (0.5 mg/kg). We found that
      the behavioral response to MP did not change during the course of chronic
      treatment and that MP-pretreated animals did not exhibit a sensitized locomotor
      response to the methamphetamine challenge. We propose that, to the extent that
      this treatment protocol more closely reflects clinical exposure patterns, the
      relative insensitivity of accumbens dopamine to the acute administration of these
      MP doses, and the corresponding absence of evidence for the development of
      locomotor sensitization, supports one clinical view that there is little abuse
      liability associated with low dose, long-term MP treatment.

PMID- 12177222
TI  - Ciproxifan, a histamine H3-receptor antagonist/inverse agonist, potentiates
      neurochemical and behavioral effects of haloperidol in the rat.
AB  - By using double in situ hybridization performed with proenkephalin and H3
      receptor riboprobes on the same sections from rat brain, we show that histamine
      H3 receptors are expressed within striatopallidal neurons of the indirect
      movement pathway. The majority ( approximately 70%) of striatal enkephalin
      neurons express H3-receptor mRNAs. This important degree of coexpression of
      proenkephalin and H3-receptor mRNAs prompted us to explore the effect of H3
      receptor ligands on the regulation of enkephalin mRNA expression in the striatum.
      Acute administration of ciproxifan, a H3-receptor antagonist/inverse agonist, did
      not modify the expression of the neuropeptide by itself but strongly increased
      the upregulation of its expression induced by haloperidol. This potentiation (1)
      was suppressed by the administration of (R)-alpha-methylhistamine, a H3-receptor
      agonist, (2) occurred both in the caudate-putamen and nucleus accumbens, and (3)
      was also observed with a similar pattern on c-fos and neurotensin mRNA
      expression. Similarly, whereas it was devoid of any motor effect when used alone,
      ciproxifan strongly potentiated haloperidol-induced locomotor hypoactivity and
      catalepsy, two behaviors in which striatal neurons are involved. The strong H3
      receptor mRNA expression in enkephalin neurons suggests that the synergistic
      neurochemical and motor effects of ciproxifan and haloperidol result from direct
      H3/D2-receptor interactions, leading to an enhanced activation of striatopallidal
      neurons of the indirect movement pathway. The potentiation of the effects of
      haloperidol by ciproxifan strengthens the potential interest of H3-receptor
      antagonists/inverse agonists to improve the symptomatic treatment of
      schizophrenia.

PMID- 12177223
TI  - Contribution of different taste cells and signaling pathways to the
      discrimination of "bitter" taste stimuli by an insect.
AB  - Animals can discriminate among many different types of foods. This discrimination
      process involves multiple sensory systems, but the sense of taste is known to
      play a central role. We asked how the taste system contributes to the
      discrimination of different "bitter" taste stimuli in Manduca sexta caterpillars.
      This insect has approximately eight bilateral pairs of taste cells that respond
      selectively to bitter taste stimuli. Each bilateral pair of bitter-sensitive
      taste cells has a different molecular receptive range (MRR); some of these taste
      cells also contain two signaling pathways with distinctive MRRs and temporal
      patterns of spiking. To test for discrimination, we habituated the caterpillar's
      taste-mediated aversive response to one bitter taste stimulus (salicin) and then
      asked whether this habituation phenomenon generalized to four other bitter taste
      stimuli (caffeine, aristolochic acid, Grindelia extract, and Canna extract). We
      inferred that the two compounds were discriminable if the habituation phenomenon
      failed to generalize (e.g., from salicin to aristolochic acid). We found that M.
      sexta could discriminate between salicin and those bitter taste stimuli that
      activate (1) different populations of bitter-sensitive taste cells (Grindelia
      extract and Canna extract) or (2) different signaling pathways within the same
      bitter-sensitive taste cell (aristolochic acid). M. sexta could not discriminate
      between salicin and a bitter taste stimulus that activates the same signaling
      pathway within the same bitter-sensitive taste cell (caffeine). We propose that
      the heterogeneous population of bitter-sensitive taste cells and signaling
      pathways within this insect facilitates the discrimination of bitter taste
      stimuli.

PMID- 12177224
TI  - Interaction of inferior temporal cortex with frontal cortex and basal forebrain:
      double dissociation in strategy implementation and associative learning.
AB  - Macaque monkeys learned a strategy task in which two groups of visual objects
      needed to be treated differently, one with persistent and one with sporadic
      object choices, to obtain food rewards. After preoperative training, they were
      divided into two surgical groups of three monkeys each. One group received
      crossed unilateral removals of frontal cortex and inferior temporal cortex (IT x
      FC) and were severely impaired in performing the strategy task. The other group
      received bilateral transection of anterior temporal stem, amygdala, and fornix
      (TS+AM+FX) and were unimpaired in performing the strategy task. Subsequently the
      same animals were tested in visual object-reward association learning. Here,
      confirming previous results, group IT x FC was unimpaired, whereas group TS+AM+FX
      was severely impaired. The results show that the amnesic effects of TS+AM+FX
      cannot be generally attributed to the partial temporal-frontal disconnection that
      this lesion creates, and therefore support the hypothesis that the amnesic
      effects of this lesion are caused primarily by the disconnection of temporal
      cortex from ascending inputs from the basal forebrain. The results also show that
      temporal-frontal interaction in strategy implementation does not require those
      routes of temporal-frontal interaction that are interrupted in TS+AM+FX, and
      therefore support the hypothesis that projections to other posterior cortical
      areas allow temporal and frontal cortex to interact with each other by
      multisynaptic corticocortical routes in strategy implementation.

PMID- 12177225
TI  - Decreased neuronal synchronization during experimental seizures.
AB  - Synchronization between CA1 pyramidal neurons was studied using dual-cell patch
      clamp techniques simultaneous with an extracellular measurement of network
      activity. We explored various linear and nonlinear methods to detect weak
      synchronization in this network, using cross-correlation, mutual information in
      one and two dimensions, and phase correlation in both broad and narrow band. The
      linear and nonlinear methods demonstrated different patterns of sensitivity to
      detect synchrony in this network, depending on the dynamical state of the
      network. Bursts in 4-amino-pyridine (4AP) were highly synchronous events.
      Unexpectedly, seizure-like events in 4AP were desynchronous events, both in
      comparison with interictal periods preceding the seizure without bursts (cut
      Schaffer collateral tract) and in comparison with bursts preceding the seizures
      (intact Schaffer collateral tract). The finding that seizure-like events are
      associated with desynchronization in such networks is consistent with recent
      theoretical work, suggesting that asynchrony is necessary to maintain a high
      level of activity in neuronal networks for sustained periods of time and that
      synchrony may disrupt such activity.

PMID- 12177226
TI  - Positive and negative motivation in nucleus accumbens shell: bivalent
      rostrocaudal gradients for GABA-elicited eating, taste "liking"/"disliking"
      reactions, place preference/avoidance, and fear.
AB  - Microinjection of the GABA(A) agonist muscimol in the rostral medial accumbens
      shell in rats elicits appetitive eating behavior, but in the caudal shell instead
      elicits fearful defensive treading behavior. To further test the hypothesis that
      rostral shell muscimol microinjections produce positive motivational states,
      whereas caudal shell muscimol produces negative states, we measured behavioral
      place preference/avoidance conditioning and affective hedonic and aversive
      orofacial expressions of taste-elicited "liking" and "disliking" (gapes, etc.) in
      addition to fear and feeding behaviors. Farthest rostral muscimol microinjections
      (75 ng) caused increased eating behavior and also caused positive conditioned
      place preferences and increased positive hedonic reactions to the taste of
      sucrose. By contrast, caudal shell microinjections elicited negative defensive
      treading and caused robust negative conditioned place avoidance and negative
      aversive reactions to sucrose or quinine tastes. Intermediate rostral
      microinjections elicited effects of mixed positive/negative valence (positive
      appetitive eating behavior but negative place avoidance and negative taste
      reactions at mid-rostral sites, and sometimes positive eating simultaneously with
      fearful defensive treading more caudally). These results indicate that GABAergic
      neurotransmission in local microcircuits in nucleus accumbens mediates
      motivated/affective behavior that is bivalently organized along rostrocaudal
      gradients.

PMID- 12177227
TI  - It's time to pay attention to attention in aging.

PMID- 12177228
TI  - Metaplastic protein phosphatases.

PMID- 12177229
TI  - Extracellular signal-regulated kinase activity in the entorhinal cortex is
      necessary for long-term spatial memory.
AB  - Lesion studies have provided evidence that the entorhinal cortex (EC)
      participates in spatial memory. However, the molecular cascades that underlie
      memory-associated changes in the EC and its specific role in spatial memory,
      however, have not been clearly delineated. Recently, it has been shown that
      activation of extracellular signal-regulated kinase (Erk, a mitogen-activated
      protein kinase family member) in the dorsal hippocampus is necessary for spatial
      memory. To examine whether similar mechanisms are used for spatial memory storage
      in the EC, Erk activity was inhibited after training in the Morris water maze.
      Bilateral infusion of the mitogen-activated protein kinase kinase inhibitor
      PD098059 into the EC immediately after training resulted in a memory deficit
      observed during a retention test performed 48 h later. This deficit was abolished
      with pretraining in a different water maze in which animals were able to learn
      the general task requirements and the appropriate search strategies. The absence
      of a deficit indicates that Erk activity in the EC may be involved in storing the
      task requirements or the search strategies. The findings presented in this
      article are consistent with the idea that the EC is involved in spatial memory
      and indicate that Erk activity is necessary for memory consolidation in this
      structure.

PMID- 12177230
TI  - Intrahippocampal wortmannin infusion enhances long-term spatial and contextual
      memories.
AB  - The transition from short- to long-term memory involves several biochemical
      cascades, some of which act in an antagonistic manner. Post-training
      intrahippocampal administration of wortmannin, a pharmacological inhibitor of
      phosphatidylinositol 3-kinase, had no effect on memory tested 3 h later, but
      improved long-term memory tested 48 h following the completion of training. This
      effect was seen in two hippocampus-dependent tasks: the Morris water maze, using
      both massed and distributed training paradigms, and contextual fear conditioning.
      The improvement of long-term memory appears to be the result of enhanced
      consolidation, as wortmannin had no effect on memory recall. These results are
      consistent with the hypothesis that memory consolidation involves competing
      processes, and that blockade of an inhibitory constraint facilitates the
      consolidation process.

PMID- 12177231
TI  - Deficits in trace cued fear conditioning in galanin-treated rats and galanin
      overexpressing transgenic mice.
AB  - Galanin inhibits the release of several neurotransmitters and produces
      performance deficits in a variety of spatial and aversive learning and memory
      tasks. The experiments in this study investigated the role galanin has in
      emotional learning and memory using a standard delay cued and contextual fear
      conditioning task. Rats were administered galanin into the lateral ventricles
      before training, and scored for freezing behavior in the same context and in a
      novel context with and without an auditory cue (CS) that had been paired
      previously with an aversive stimulus (US). Galanin-overexpressing transgenic mice
      were tested in an identical behavioral protocol. The galanin-administered rats
      and the transgenic mice were not significantly different from their respective
      controls on this task. A more challenging trace cued and contextual fear
      conditioning procedure was administered to separate groups of galanin-treated
      rats and galanin-overexpressing transgenic mice. Subjects were trained with the
      same CS and US, however, a 2.5-sec delay was inserted between CS offset and US
      onset. Following the trace conditioning, rats administered galanin and mice
      overexpressing galanin both exhibited significantly less freezing to the CS in
      the novel context as compared with their control groups. These results indicate
      that the observed disruption of cued fear conditioning was specific to the more
      difficult trace conditioning task. These findings are the first demonstration
      that galanin impairs performance on an emotional memory task and support the
      hypothesis that galanin-induced deficits are specific to more difficult cognitive
      tasks.

PMID- 12177232
TI  - Aged rats are impaired on an attentional set-shifting task sensitive to medial
      frontal cortex damage in young rats.
AB  - Normal aging is associated with disruption of neural systems that subserve
      different aspects of cognitive function, particularly in the hippocampus and
      frontal cortex. Abnormalities in hippocampal function have been well investigated
      in rodent models of aging, but studies of frontal cortex function in aged rodents
      are few. We tested young (4-5 mo old) and aged (27-28 mo old) male Long-Evans
      rats on an attentional set-shifting task modified slightly from previous
      publication. After training on two problems in which the reward was consistently
      associated with the same stimulus dimension, and a reversal of one problem, a new
      problem was presented in which the reward was consistently associated with the
      previously irrelevant stimulus dimension (extradimensional shift [EDS]). Aged
      rats as a group were significantly impaired on the EDS, although some individual
      aged rats performed as well as young rats on this phase. In addition, some aged
      rats were impaired on the reversal, although a group effect did not reach
      significance in this phase. Impairment in neither reversal nor EDS was associated
      with impairments in spatial learning in the Morris water maze. Young rats with
      neurotoxic lesions of medial frontal cortex are also selectively impaired on the
      EDS. These results indicate that normal aging in rats is associated with impaired
      medial frontal cortex function. Furthermore, age-related declines in frontal
      cortex function are independent of those in hippocampal function. These results
      provide a possible basis for correlating age-related changes in neurobiological
      markers in frontal cortex with cognitive decline.

PMID- 12177235
TI  - Role and function of the 26S proteasome in proliferation and apoptosis.
AB  - The 26S proteasome constitutes the central proteolytic machinery of the highly
      conserved ubiquitin/proteasome system, the cell's major tool for extralysosomal
      protein degradation. Recently, a plethora of cell proteins implicated in the
      regulation of basic cellular processes, such as proliferation, differentiation,
      cell cycling, and apoptosis have been discovered to undergo processing and
      functional limitation by entering the ubiquitin/proteasome pathway with the final
      destination to be proteolytically degraded by the 26S proteasome. Because both
      negative and positive regulators of proliferation and apoptosis undergo
      proteasomal degradation in a tightly regulated and temporally controlled fashion,
      the 26S proteasome can play opposite roles in the regulation of proliferation and
      apoptosis. These roles are apparently defined by the cell's environment and
      proliferative state. Finally, proteasomal protein degradation is deregulated in a
      number of human diseases, including cancer and neurodegenerative and
      myodegenerative diseases, which all exhibit an imbalance of proliferation and
      apoptosis. An improved understanding of the modes of proteasomal action should
      lead to the development of beneficial therapeutic and diagnostic strategies in
      the future.

PMID- 12177233
TI  - "Silent" metaplasticity of the late phase of long-term potentiation requires
      protein phosphatases.
AB  - The late phase of long-term potentiation (L-LTP) is correlated with some types of
      long-term memory, but the mechanisms by which L-LTP is modulated by prior
      synaptic activity are undefined. Activation of protein phosphatases by low
      frequency stimulation (LFS) given before induction of L-LTP may significantly
      modify L-LTP. Using cellular electrophysiological recording methods in mouse
      hippocampal slices, we show that LFS given before induction of L-LTP inhibited L
      LTP in an activity-dependent manner without affecting either basal synaptic
      strength or the early phase of LTP (E-LTP). This anterograde inhibitory effect of
      LFS was persistent, required N-methyl-D-aspartate (NMDA) receptor activation, and
      was blocked by inhibitors of protein phosphatase 1 (PP1) and protein phosphatase
      2A (PP2A). These data indicate that certain patterns of LFS can activate PP1
      and/or PP2A, and that long-lasting activation of these phosphatases by prior LFS
      can suppress the subsequent expression of L-LTP without affecting E-LTP. Because
      this inhibition of L-LTP is caused by prior synaptic activity that, alone,
      produced no net effect on synaptic efficacy, we suggest that this is a "silent"
      form of metaplasticity that may influence long-term information storage by
      modulating the capacity of synapses to express L-LTP after repeated bouts of
      activity.

PMID- 12177236
TI  - Study of the mechanism involved in angiogenesis and synovial cell proliferation
      in human synovial tissues of patients with rheumatoid arthritis using SCID mice.
AB  - To examine whether synovial cell proliferation is due to angiogenesis, we studied
      the relationship between the inhibition of synovial cell proliferation and an
      angiogenesis inhibitor, TNP-470, in human synovial tissues. Human synovial
      tissues were implanted into the back of SCID mice (SCID-HuAg mice). Sixteen mice
      were divided into two groups of eight mice each: the untreated group (vehicle
      group) and the TNP-470-treated group that received a dose of 10 mg/kg body weight
      by subcutaneous injection. The number of blood vessels and synovial lining cells
      clearly increased in the vehicle group, but the number of synovial lining cells
      clearly decreased and the blood vessels were hardly detected in the TNP-470
      group. Immunohistochemically, cells that stained positively for the anti
      proliferating cell nuclear antigen (PCNA) mAb were abundant in synovial lining
      cells and endothelial cells in synovial tissues. Cells that stained positively
      for the anti-CD34 polyclonal antibody were abundant in the endothelial cells in
      the vehicle group, but these positively stained cells were hardly detected in the
      TNP-470 group. The PCNA positivity ratio in the vehicle group was 0.64 +/- 0.019,
      whereas that in the TNP-470 group was 0.199 +/- 0.007. The numbers of cells that
      stained positively for anti-CD34 polyclonal antibody were 242 +/- 13.4 in the
      vehicle group and 153 +/- 6.73 in the TNP-470 group per 10 microscopic fields.
      Cells that stained positively for anti-mouse CD31 mAb were mainly localized in
      the synovial lining, but invaded the subsynovial lining layer in human synovial
      tissues. On the other hand, cells that stained positively for anti-human CD31 mAb
      were mainly localized in the subsynovial lining layer. We found that endothelial
      cell proliferation is dependent on angiogenesis based on the result that
      angiogenesis and synovial cell proliferation were inhibited by treatment with TNP
      470.

PMID- 12177237
TI  - Polarized expression of cystic fibrosis transmembrane conductance regulator and
      associated epithelial proteins during the regeneration of human airway surface
      epithelium in three-dimensional culture.
AB  - We have previously shown that, in normal human airway tissue, localization of the
      cystic fibrosis transmembrane conductance regulator (CFTR) can be affected by
      epithelial maturation, polarity, and differentiation and that CFTR trafficking
      and apical localization depend on the integrity of the airway epithelium. In this
      study, we addressed the question of whether the three-dimensional (3-D)
      organization of adult human airway epithelial cells in suspension culture under
      rotation, leading to spheroid-like structures, could mimic the in vivo phenomenon
      of differentiation and polarization. The kinetics of the differentiation,
      polarity, and formation of the CFTR-ZO-1-ezrin complex was analyzed by
      transmission, scanning, and immunofluorescence microscopy. Functional activity of
      the airway surface epithelium was assessed by monitoring the degree of cAMP
      stimulated chloride efflux from cultured cells. Our results show that after the
      initial step of dedifferentiation, characterized by a loss of ciliated cells and
      disappearance of epithelial subapical CFTR-ezrin-ZO-1 complex, the isolated cells
      formed 3-D spheroid structures within 24 hours. After 15 days, progressive
      ciliogenesis was observed and secretory cells could be identified. After 35 days
      of 3-D culture, ZO-1, CFTR, ezrin, and CD59 were apically or subapically located,
      and well-differentiated secretory and ciliated cells were identified. CFTR
      functionality was assessed by analyzing the Cl(-) secretion after amiloride and
      forskolin perfusion. After 35 days of culture of spheroids in suspension, a
      significant increase in Cl(-) efflux was observed in well-differentiated ciliated
      cells.

PMID- 12177238
TI  - Renal injury in apolipoprotein E-deficient mice.
AB  - Hyperlipidemia is thought to accelerate the progression of renal diseases, but
      the mechanisms by which hyperlipidemia exerts its deleterious effect is still
      poorly understood. The aim of this study was to describe the renal pathology in a
      hyperlipidemic mouse strain, the apolipoprotein E-deficient mice (apoE-/-). Renal
      specimens from a total of 34 mice were studied, including 19 apoE-/- females at
      the age of 36 weeks, 9 apoE-/- females at the age of 24 weeks, and 6 wild-type
      females (C57BL/6) as controls. Kidneys were evaluated by histologic examination,
      immunohistochemistry, and electron microscopy. Immunohistochemistry was used to
      detect MAC-2-expressing monocyte/macrophages, and the proliferation marker PCNA.
      Glomerular cell number, glomerular matrix area, and glomerular area were
      quantified by morphometry. Glomerular lesions in apoE-/- mice were characterized
      by macrophage accumulation, commonly with foam cell appearance, deposition of
      extracellular matrix, glomerular hyperplasia, and at times prominent
      mesangiolysis associated with capillary microaneurysms. Some cases demonstrated
      lipid deposits filling glomerular capillaries. Arterioles of the vascular pole
      demonstrated a "foamy" degeneration of smooth muscle cells. These lesions related
      to hyperlipidemia in this well-established mouse strain have not been previously
      described. Because this mouse strain is among the most widely studied for
      interventions aimed at altering hyperlipidemia and the progression of
      atherosclerosis, we believe that our observations may be of major importance for
      the accurate interpretation of interventional studies in this strain and offer a
      new opportunity to study mechanisms of hyperlipidemic renal injury.

PMID- 12177239
TI  - Chromogenic in situ hybridization: a novel approach to a practical and sensitive
      method for the detection of HER2 oncogene in archival human breast carcinoma.
AB  - The high incidence of HER2 overexpression on the cell surface of breast cancer
      cells and the recognized prognostic and potentially predictive value of HER2
      render this cell surface receptor a novel and important therapeutic target.
      Although immunohistochemistry (IHC; HercepTest) and fluorescence in situ
      hybridization (FISH; PathVysion and INFORM)-both approved by the Food and Drug
      Administration-have emerged as the most viable assays for evaluation of HER2
      status in routine clinical practice, there is still no consensus on which is the
      best method for assessing HER2 status. Therefore, our specific objective was to
      establish a chromogenic in situ hybridization (CISH) assay for the detection of
      HER2 amplification on a cohort of 173 archival invasive breast carcinomas.
      Results were compared with HercepTest, which is the most frequently used method
      for detecting HER2 alteration. Additionally, HER2 gene copy number was
      investigated using differential PCR (dPCR) as a testing system. HER2
      overexpression was found by IHC in 24.3%; HER2 amplification was found by CISH in
      19.1% and by dPCR in 9.2% of the tumors. The overall concordance rate was 95.9%
      between CISH and IHC and 85.0% between dPCR and IHC. Kappa statistics revealed an
      excellent agreement between IHC and CISH (kappa = 0.878), but only a moderate
      agreement was found between IHC and dPCR (kappa = 0.482). Discrepant cases
      between CISH and HercepTest and all IHC-positive cases (+2 and +3), a total of 42
      cases, were analyzed with the FISH PathVysion (Vysis) assay. Among 25 HercepTest
      positive cases (score +3), 2 showed no gene amplification by FISH or CISH. Four
      of 13 tumors with weak HER2 overexpression (score +2) were negative with both
      FISH and CISH. Concordance between CISH and FISH was 100% for the 38 cases
      analyzed. The current study showed that CISH represents a practical and simple
      assay for evaluating HER2 gene amplification in archival material, offering a
      promising alternative to IHC or FISH for the routine diagnostic setting.

PMID- 12177240
TI  - Differential role of neutrophils and alveolar macrophages in hepatocyte growth
      factor production in pulmonary fibrosis.
AB  - Neutrophils may participate in the development of lung fibrosis. Hepatocyte
      growth factor (HGF), a growth factor for type II pneumocytes, is produced by
      neutrophils. We measured the production of HGF by blood and alveolar neutrophils
      from patients with either idiopathic pulmonary fibrosis (n = 11) or connective
      tissue disease-associated pulmonary fibrosis (n = 10) and from control patients
      (n = 10). HGF secretion by alveolar macrophages and the expression of the HGF
      receptor by alveolar epithelial cells in pulmonary fibrosis were also evaluated.
      HGF was not detected in bronchoalveolar lavage fluid from controls. HGF
      concentration in the epithelial lining fluid from patients was 4-fold higher than
      in plasma, suggesting a local production within the alveolar space. Alveolar
      neutrophils secreted HGF in vitro. Basal HGF secretion by alveolar neutrophils
      positively correlated with HGF in the epithelial lining fluid (p = 0.05, rho =
      0.582). HGF secretion by alveolar neutrophils could not be further stimulated
      with lipopolysaccharide, whereas HGF secretion by blood neutrophils doubled with
      lipopolysaccharide. Alveolar macrophages did not secrete HGF in vitro. The
      expression of the HGF receptor was greatly increased in the fibrotic lung,
      supporting the local function of HGF secreted by neutrophils. We conclude that
      neutrophils are a source of HGF in patients with pulmonary fibrosis.

PMID- 12177241
TI  - Loss of T-cadherin (CDH13, H-cadherin) expression in cutaneous squamous cell
      carcinoma.
AB  - We previously reported that T-cadherin (CDH13, H-cadherin), a unique cadherin
      molecule, was expressed on the basal cell layer in normal murine and human
      epidermis. In the present study, T-cadherin expression in archival human skin
      specimens comprising a spectrum of human squamous cell neoplasia was
      investigated. T-cadherin expression was observed in both normal epidermal basal
      cells and adnexal epithelial cells of formalin-fixed and paraffin-embedded tissue
      sections. Western immunoblotting also revealed that mature T-cadherin protein was
      expressed in cultured human skin tissue equivalent. Atypical keratinocytes in 27
      of 53 specimens of actinic keratosis and 23 of 30 specimens of Bowen's disease
      expressed T-cadherin. In contrast, T-cadherin was focally expressed in 6 of 56
      invasive cutaneous squamous cell carcinomas. To explore the molecular mechanism
      of down-regulation of T-cadherin expression in invasive squamous cell carcinoma,
      loss of heterozygosity, genetic alternations, and methylation status in the 5'
      region of the T-cadherin gene were investigated. Loss of heterozygosity at intron
      1 of the T-cadherin gene was observed in 8 of 28 informative cases of invasive
      squamous cell carcinoma. Although no structural genomic alternations were found
      by sequence analysis, aberrant promoter methylation of the T-cadherin gene was
      found in 12 of 28 invasive squamous cell carcinomas. T-cadherin expression was
      restored in cultured A431 cells, in which aberrant methylation was found by
      treatment with the demethylating agent 5'-aza-2-deoxycytidine. These findings
      suggest that a combination of deletion and aberrant methylation of the T-cadherin
      gene may play a role in loss of gene expression in a considerable number of
      invasive cutaneous squamous cell carcinomas.

PMID- 12177242
TI  - Control of melanoma morphogenesis, endothelial survival, and perfusion by
      extracellular matrix.
AB  - The morphogenetic properties of endothelial cells and melanoma cells were tested
      under varying matrix quantities and distributions and under constant and
      saturating levels of growth factors. Aggressive melanoma cells self-assembled
      into cords vasculogenically only when seeded on thin matrices: nonaggressive
      melanoma cells did not mimic endothelial cell behavior under any matrix
      thickness. When buried in matrix, however, aggressive melanoma cells generated
      looping patterns that contained tumor cells and matrix. These patterns were
      different topologically and compositionally from cord-like structures or blood
      vessels but were nevertheless capable of conducting dye by microinjection or
      passive diffusion. When seeded on three-dimensional cultures of nonaggressive
      nonpattern-forming melanoma cells, prelabeled endothelial cells attached to,
      penetrated through, and survived for 2 weeks but failed to form vasculogenic
      cords. In cocultures containing aggressive melanoma cells, endothelial cells
      survived briefly but formed short cords only in contact with looping patterns
      formed by the aggressive tumor cells. Time-lapse recording showed that
      endothelial cells were lysed upon direct contact with aggressive melanoma cells.
      Looping patterns identified in human tissue samples were composed
      ultrastructurally of electron-dense material on either side of a layer of tumor
      cells; scattered red blood cells were seen in this central cellular layer. By
      immunohistochemistry, patterns labeled with laminin and fibrinogen colocalized to
      these looping laminin-positive patterns, suggesting the presence of plasma within
      these patterns from contiguous leaky tumor vessels. These observations are
      consistent with the perfusion of these patterns in vitro and with repeated
      demonstrations of the colocalization of intravenous tracers to looping laminin
      patterns in animal xenograft models by independent groups. Thus, the distribution
      and localized quantity of extracellular matrix in aggressive melanomas
      contributes to the regulation of tumor cell morphogenesis, modulates interactions
      between tumor cells and endothelial cells, and may contribute to an extravascular
      matrix-directed circulation.

PMID- 12177243
TI  - Association of spasmolytic polypeptide-expressing metaplasia with carcinogen
      administration and oxyntic atrophy in rats.
AB  - Spasmolytic polypeptide (TFF2)-expressing metaplasia (SPEM) is a gastric
      metaplastic lineage associated with the development of intestinal-type gastric
      adenocarcinoma. To study the etiology of this potential neoplastic precursor
      metaplasia, we used surgical rat models of remnant gastric adenocarcinoma studied
      with and without exposure to nitroso carcinogen. Animals with truncal vagotomy
      without duodenogastric reflux procedures demonstrated normal mucous neck cell
      spasmolytic polypeptide (SP) immunostaining. In these animals, anti-proliferating
      cell nuclear antigen (PCNA)-labeled nuclei were found in the normal midgland
      progenitor zone. Rats that received anatomic alterations that augmented the
      degree of duodenogastric reflux, however, revealed expansion of basally placed SP
      immunoreactive cells with early phenotypic changes of SPEM. Seventy percent of
      animals with antrectomy and carcinogen (with or without vagotomy) developed SPEM
      at the base of the gastric mucosa. In association with the appearance of this
      metaplastic lineage, a distinct second zone of PCNA-labeled nuclei developed in
      the deepest portion of the mucosa. Of interest, three animals demonstrating these
      changes developed intestinal-type gastric adenocarcinoma. Finally, we studied the
      immunostaining pattern of intrinsic factor, normally a chief cell marker in rat
      fundic mucosa. In animals with SPEM, we observed coexpression of SP and intrinsic
      factor in SPEM cells at the base of the mucosa. These findings support our
      hypothesis that SPEM develops from a second progenitor cell population,
      reflecting either the unmasking of a cryptic zone or transdifferentiation of
      chief cells.

PMID- 12177244
TI  - Dystroglycan expression in hepatic stellate cells: role in liver fibrosis.
AB  - Dystroglycan is a membrane component of the dystrophin-glycoprotein transmembrane
      complex. Its expression is required for the spatial organization of laminin on
      the cell surface and for basement membrane assembly. In view of the constitution
      of a perisinusoidal basement membrane during liver fibrosis, we studied
      dystroglycan expression in liver fibrosis. Dystroglycan mRNA and protein
      expression were investigated by immunofluorescence, Western blot, and
      quantitative RT-PCR (TaqMan) in normal human and rat liver and in isolated rat
      hepatic stellate cells. On Western blot, a 43-kd band corresponding to beta
      dystroglycan was observed in protein extracted from normal and fibrotic human and
      rat livers. The specific 43-kd protein was also detected in lysates from rat
      hepatic stellate cells but not from hepatocytes. By immunofluorescence, patchy
      deposits of beta-dystroglycan were detected on membrane of hepatic stellate cells
      in culture. On Western blot and quantitative RT-PCR, an up-regulation of beta
      dystroglycan was shown during spontaneous activation of hepatic stellate cells in
      culture. Direct evidence for the role of dystroglycan in laminin-hepatic stellate
      cell interaction was shown because specific antibody directed against alpha
      dystroglycan inhibited partially hepatic stellate cell adhesion on laminin-coated
      plates. This mechanism was calcium dependent because EDTA inhibited cell/laminin
      adhesion, an effect reversed by addition of Ca(2+). This study shows that
      dystroglycan is expressed on the membrane of hepatic stellate cells and is up
      regulated during liver fibrosis. Dystroglycan interaction with laminin should be
      implicated in the concentration of pericellular laminin and in the constitution
      of a perisinusoidal basement membrane during liver fibrosis.

PMID- 12177245
TI  - Acceleration of cutaneous wound healing by transient p53 inhibition.
AB  - The increase of cell proliferation during early wound healing is thought to be
      regulated by a decrease of apoptosis. In contrast, the reduction of cellularity
      during final wound maturation may be controlled by an increase of apoptotic cell
      death. Herein we studied whether p53 is involved in wound healing-associated
      apoptosis and whether transient inhibition of p53 is effective to improve the
      early healing process of cutaneous wounds. Using intravital microscopic and
      immunohistochemical techniques in hairless mice, we demonstrated that in vivo
      inhibition of p53 by pifithrin-alpha (PFT-alpha; 2.2 mg/kg ip) accelerates early
      epithelialization and neovascularization of cutaneous wounds by (i) promoting
      leukocyte recruitment, (ii) increasing cell proliferation, and (iii) reducing
      apoptotic cell death. We further show that final wound closure with down
      regulation of cell proliferation is not inhibited by PFT-alpha treatment,
      indicating that transient blockade of p53 function does not affect the process of
      wound maturation. Western blot analysis revealed that PFT-alpha lowered nuclear
      but not cytoplasmic p53, implying that cytoplasmic retention of p53 mediates the
      antiapoptotic effects of PFT-alpha. Furthermore, PFT-alpha significantly
      increased expression of proliferating cell nuclear antigen protein in whole
      extracts of cutaneous tissue and caused a rise in proliferation of wild-type, but
      not mutant, p53-expressing keratinocytes. From our study we conclude that
      transient inhibition of p53 supports the early cell proliferation required for
      rapid tissue repair and that this may represent an attractive approach in the
      treatment of delayed wound healing.

PMID- 12177246
TI  - The helix-loop-helix protein id-1 delays onset of replicative senescence in human
      endothelial cells.
AB  - Id proteins are negative regulators of basic helix-loop-helix transcription
      factors, which are critical for expression of genes associated with cellular
      differentiation. Previous studies have shown that overexpression of Id-1 delays
      cellular senescence in several cell types, including fibroblasts, mammary
      epithelial cells, and keratinocytes. Although previous studies have demonstrated
      the expression of Id-1 in endothelium, the regulation of Id-1 has not been
      studied in these cells. In this report, a retroviral vector was used to
      overexpress Id-1 in human endothelial cells. Sustained expression of Id-1
      resulted in a 2- to 3-fold increase in the total number of population doublings
      (replicative capacity) of the cells compared with vector-treated controls, which
      correlated with low levels of p16, p21, and p27 expression. The cells, however,
      were not immortalized and did eventually undergo senescence despite elevated Id-1
      levels. Senescence was characterized by a dramatic increase in p16, but not p21
      and p27. Under these experimental conditions, telomerase activity was not
      detected and the telomeres became progressively shorter with time. These results
      demonstrate the importance of Id-1 in endothelial cell proliferation and indicate
      that Id-1 represses p16 expression, resulting in delayed senescence. These
      findings may have implications in the development of endothelial cell-derived
      tumors.

PMID- 12177247
TI  - Proximal tubular epithelial cell integrins respond to high glucose by altered
      cell-matrix interactions and differentially regulate matrixin expression.
AB  - Thickening of the tubular basement membrane (TBM) occurs in diabetic nephropathy,
      but the effects of high glucose on the functional aspects of proximal tubular
      epithelial cells are not clearly understood. In the present study, we examined
      the effects of elevated glucose concentrations on (a) integrin expression by
      human proximal tubular epithelial cells (HK-2) and integrin-mediated interactions
      with type IV collagen (colIV) and laminin, major components of TBM; (b) the
      expression of matrixins/matrix metalloproteinases (MMPs), which is regulated by
      integrins; and (c) the expression of tissue inhibitors of metalloproteinases
      (TIMPs). HK-2 cells cultured in 25 mM glucose underwent a reduction of the
      expression of alpha3, beta1, alpha(v)beta3, and alpha5 integrin subunits, with a
      concomitant increase of the alpha2 subunit, compared with cells grown in 5 mM
      glucose. Adhesion experiments demonstrated that high glucose led to increased
      cell adhesion on either colIV or laminin. Experiments of competition of adhesion
      using anti-integrin antibodies indicated that HK-2 cells in 5 mM glucose used
      mainly alpha(v)beta3 and alpha5beta1 integrins to adhere to colIV, whereas in 25
      mM glucose they additionally used alpha2beta1. In the case of laminin, a beta1
      mediated adhesion was observed when HK-2 cells were in 5 mM glucose, whereas in
      25 mM glucose, alpha2beta1 and alpha(v)beta3 were also involved. Elevated glucose
      concentrations resulted in decreased expression of MMP-9 and MMP-2, whereas an
      increase in TIMP-1 and a decrease in TIMP-2 expression were observed. We also
      examined which integrins mediated the expression and secretion of matrixins MMP-2
      and MMP-9. Ligation of alpha3beta1 with mAbs resulted in induction of MMP-2
      expression and secretion, whereas antibody ligation of alpha(v)beta3 led to down
      regulation of MMP-9. The above data implicate integrins of proximal tubular
      epithelial cells in the regulation of MMPs and in the development of TBM
      thickening in diabetic nephropathy.

PMID- 12177248
TI  - Molecular and standard approaches to the diagnosis of mycobacterial granulomatous
      lymphadenitis in paraffin-embedded tissue.

PMID- 12177249
TI  - Parental smoking cessation and adolescent smoking.
AB  - OBJECTIVE: To examine the relation of parent smoking cessation to adolescent
      smoking and test its potential mediators. METHOD: Participants were 446
      adolescents and their parents who completed a computerized measure of implicit
      attitudes toward smoking and questionnaires assessing smoking, parenting, and
      explicit attitudes. RESULTS: Parental smoking cessation was associated with less
      adolescent smoking, except when the other parent currently smoked. In general, ex
      smoking parents showed more antismoking socialization than did smoking parents.
      However, in children's reports, these effects were negated if the other parent
      (particularly the mother) smoked. Children's reports of parents' antismoking
      behavior partially mediated the relation between parental smoking and adolescent
      smoking. Although children's implicit and explicit attitudes were unrelated to
      parental smoking, mothers' implicit attitudes were related to both their own
      smoking and their child's smoking. CONCLUSIONS: Parental smoking cessation may
      help lower risk for adolescent smoking. However, this benefit may be realized
      only if the other parent does not currently smoke. Antismoking parenting might be
      a useful focus in cessation interventions.

PMID- 12177250
TI  - Cigarette smoking and perceived health in school dropouts: a comparison of
      Mexican American and non-Hispanic white adolescents.
AB  - OBJECTIVE: To examine the relations between educational attainment and health
      (cigarette smoking and perceived health) in Hispanic adolescents. METHOD:
      Participants included 3,360 Mexican American and non-Hispanic white adolescents
      ranging in age from 12 to 21 years. The sample included school dropouts,
      academically at-risk students, and control students. RESULTS: School dropouts
      were 6.46 times more likely and academically at-risk students were 2.80 times
      more likely to smoke heavily than were control students. In addition, school
      dropouts reported poorer health than did their peers. Results suggest that the
      relation between educational attainment and perceived health is mediated by
      cigarette smoking. CONCLUSIONS: Increased awareness of educational attainment as
      a significant risk factor for smoking in Hispanic adolescents will enable smoking
      cessation services to be targeted more effectively.

PMID- 12177251
TI  - The role of self-assessed health in the relationship between gender and
      depressive symptoms among adolescents.
AB  - OBJECTIVE: To examine the concurrent and longitudinal relations between gender,
      self-assessed health (SAH), and depressive symptoms among adolescents. METHOD:
      Two measures of SAH (physical symptom reports and global health ratings) and a
      measure of depression were completed on two occasions over two years by 232
      adolescent boys and girls. RESULTS: Physical symptom reports were related to
      depressive symptoms both concurrently and longitudinally. Longitudinal path
      analysis revealed a significant path from gender to physical symptom reports
      (Wave 1) to depressive symptoms (Wave 2). Although global health ratings were
      related to depressive symptoms concurrently, the prospective relation was not
      significant in the cross-lagged path model. CONCLUSIONS: These findings suggest
      that the development of poorer SAH, particularly the perception of physical
      symptoms, may place adolescent girls at risk for subsequent depressive symptoms.
      Potential mechanisms for the SAH-depression relationship are discussed.

PMID- 12177252
TI  - Predictors of risky sexual behavior in African American adolescent girls:
      implications for prevention interventions.
AB  - OBJECTIVE: To describe empirically the risky sexual behavior of an at-risk sample
      of adolescent girls, to assess psychosocial correlates of risky behavior, and to
      examine the utility of applying a risk and protective model to predicting teens'
      risky sexual behavior. METHOD: Participants included 158 African American girls,
      ages 12 to 19, who were receiving medical care in an adolescent primary care
      clinic. Teens completed measures of depression, conduct problems, substance use,
      peer norms, social support, HIV knowledge, sexual self-efficacy, and sexual
      behavior. RESULTS: Teens in this sample reported high rates of risky sexual
      behaviors, including early sexual debuts and frequent unprotected sexual
      encounters with multiple partners. African American girls who reported high rates
      of substance use and who reported that their peers engaged in risky behaviors
      also reported engaging in high rates of risky sexual behaviors. Little support
      was obtained for protective factors (HIV knowledge, social support, sexual self
      efficacy) moderating the relations between risk factors and adolescents' risky
      sexual behavior in this sample. CONCLUSIONS: Teens presenting in primary care
      settings in urban environments seem to be at high risk for HIV, STDs, and
      substance abuse, and risk reduction strategies should be introduced during the
      preteen years. An interdisciplinary model of care in primary care settings
      serving adolescents is clearly indicated, and prevention-oriented interventions
      aimed at reducing risky behaviors and preventing the development of more
      significant health, mental health, or substance abuse disorders are needed.

PMID- 12177253
TI  - Weight control behaviors among obese, overweight, and nonoverweight adolescents.
AB  - OBJECTIVE: To evaluate weight control behaviors, eating, and physical activity
      behaviors among obese, overweight, and nonoverweight female and male adolescents.
      METHODS: A representative sample of 8,330 7th, 9th, and 11th grade public school
      students in Connecticut participated in the study. Adolescents responded to
      questions about weight control behaviors (dieting, exercise, vomiting, diet
      pills, and laxatives), healthy eating behaviors, breakfast consumption, and
      vigorous physical activity. RESULTS: In comparison to nonoverweight youths,
      overweight adolescents were less likely to eat breakfast and less likely to
      engage in vigorous physical activity than nonoverweight youths. Higher
      prevalences of unhealthy weight control behaviors were evident among overweight
      youths. CONCLUSIONS: Overweight adolescents use more unhealthy weight management
      strategies and are not engaging in healthier strategies, such as increased
      physical activity or healthier eating. These findings suggest the need to provide
      consistent messages about healthy weight loss methods to adolescents.

PMID- 12177254
TI  - Adolescent health risk behavior: when do pediatric psychologists break
      confidentiality?
AB  - OBJECTIVE: To determine the circumstances under which pediatric psychologists
      believe it is ethical to break confidentiality when presented with adolescent
      health risk behavior. METHOD: Members of the Society of Pediatric Psychology (N =
      92) responded to a survey containing a vignette about an adolescent patient
      engaging in health-compromising behaviors. Participants rated the degree to which
      it is ethical to break confidentiality for health risk behaviors of varying
      frequency, intensity, and duration. RESULTS: Respondents generally find it
      ethical to break confidentiality when health risk behaviors are more intense,
      more frequent, and of longer duration. Respondents also find it more ethical to
      break confidentiality for female smoking than for male smoking. Similarly, they
      find it more ethical to break confidentiality for female sexual behavior than for
      male sexual behavior, but only as the frequency/duration increases. CONCLUSIONS:
      At a certain point, maintaining the adolescent's health is more important for
      pediatric psychologists than maintaining confidentiality.

PMID- 12177255
TI  - National bone and joint decade: 2002-2011. A proclamation by the President of the
      United States of America.

PMID- 12177257
TI  - A prospective, randomized study of preoperative autologous donation for hip
      replacement surgery.
AB  - BACKGROUND: Preoperative autologous blood donation is commonly performed to meet
      potential perioperative transfusion needs and is a common practice prior to total
      hip arthroplasty. Using standardized transfusion guidelines, we prospectively
      analyzed the effectiveness of preoperative autologous donation as a method for
      decreasing allogeneic transfusion among patients undergoing unilateral primary
      total hip replacement who were eligible to donate autologous blood. METHODS:
      Patients who were scheduled for primary total hip replacement surgery and who had
      a preoperative baseline hemoglobin level >or=120 g/L were randomized either to
      donate two units of blood (autologous donors) or not to donate any blood
      (nondonors). The donors and nondonors were compared with regard to demographic
      data, blood-loss volumes, hemoglobin measurements, and transfusion rates.
      Randomization continued until data were obtained from at least forty patients per
      treatment group. RESULTS: Of the ninety-six patients who completed the study,
      forty-two were autologous donors and fifty-four were nondonors. There were no
      significant differences between the donors and nondonors with regard to age,
      male:female ratio, estimated blood volume, baseline physical condition, or
      operative blood loss. The hemoglobin values at the time of enrollment (baseline),
      at the time of hospital discharge, and six weeks postoperatively were not
      significantly different between the two groups, although values at the time of
      admission (129 +/- 13 g/L versus 138 +/- 12 g/L) and in the recovery room (104 +/
      12 g/L versus 115 +/- 13 g/L) were significantly lower in the autologous donor
      group (p < 0.05). No patient in either group required an allogeneic transfusion.
      Twenty-nine (69%) of the forty-two donors received an autologous transfusion.
      Thirty-four (41%) of eighty-two autologous units were wasted. At a charge of $379
      per autologous unit, there was an additional cost of $758 for each patient in the
      donor group. CONCLUSIONS: Preoperative autologous donation provided no benefit
      for nonanemic patients undergoing primary total hip replacement surgery.
      Preoperative autologous donation increased the likelihood of autologous
      transfusion, wastage of predonated units, and costs.

PMID- 12177258
TI  - Prophylactic pinning of the contralateral hip in slipped capital femoral
      epiphysis : evaluation of long-term outcome for the contralateral hip with use of
      decision analysis.
AB  - BACKGROUND: The risk of a contralateral slip in patients who are first seen with
      a unilateral slipped capital femoral epiphysis has been reported to be 2335 times
      higher than the risk of an initial slip. The overall prevalence of bilaterality
      varies widely throughout the literature, with some reports indicating rates as
      high as 80%. This finding has led many authors to recommend prophylactic pinning
      of the contralateral asymptomatic hip in patients presenting with a unilateral
      slipped capital femoral epiphysis. METHODS: A decision analysis model with
      probabilities for the occurrence of contralateral slip and for the severity of
      slip at different intervals of follow-up was used in the present study. These
      probabilities were compared with those for various outcomes when the
      contralateral hip is prophylactically pinned. Scores representing long-term
      outcome, according to the Iowa hip-rating system, were used in the model as a
      measure of utility. The probabilities of contralateral slip and the rates of slip
      severity were taken from large retrospective series. All meaningful clinical
      scenarios with regard to long-term outcome for the hip were considered in the
      model. Variables of uncertainty were subjected to sensitivity analyses in order
      to explore the effect on outcome over the range of plausible values for variables
      of interest. RESULTS: The results showed a benefit in the long-term outcome for
      patients who had prophylactic pinning of the contralateral hip. The threshold
      level at which a benefit is obtained with prophylactic pinning is expressed
      according to the rates of sequential slip, rates of slips overlooked at follow
      up, and complications associated with prophylactic pinning of the contralateral
      hip. CONCLUSIONS: The decision model shows that, when pooled data are used to
      predict probabilities of sequential slip, treatment of the contralateral hip with
      prophylactic pinning is beneficial to the long-term outcome for that hip. When
      considering prophylactic pinning of the contralateral hip, the clinician should
      use sound clinical judgment with respect to the age, sex, and endocrine status of
      the patient. Long-term follow-up studies are needed to establish the efficacy of
      prophylactic pinning, but the predictions in the present study, which are based
      on findings in the literature, support the safety of this procedure.

PMID- 12177259
TI  - Open reduction and internal fixation of humeral nonunions : a biomechanical and
      clinical study.
AB  - BACKGROUND: Several studies have compared different methods for fixation of the
      midpart of the humeral shaft, but there are only scattered data regarding which
      type of plate construct provides the best fixation for humeral nonunion. The
      objectives of this study were (1) to obtain objective data on the performance of
      four different plate constructs used for fixation of humeral nonunion, and (2) to
      report our clinical experience with plate fixation of thirty-seven nonunions of
      the midpart of the humeral shaft. METHODS: In the first part of the study, four
      plate constructs were compared in a Sawbones model. The groups consisted of (1) a
      posterior limited-contact dynamic compression plate alone; (2) a posterior
      limited-contact dynamic compression plate and an interfragmentary screw; (3) a
      posterior limited-contact dynamic compression plate, a lateral 3.5-mm
      reconstruction plate, and an interfragmentary screw; and (4) a posterior limited
      contact dynamic compression plate and a lateral 3.5-mm reconstruction plate.
      Tests were performed with use of an MTS Bionix machine in anterior-posterior four
      point bending, medial-lateral four-point bending, and external rotation torque.
      In the second part of the study, the charts of thirty-seven consecutive patients
      in whom a nonunion of the midpart of the humeral shaft had been treated with
      plate fixation were reviewed retrospectively. The average age of the patients was
      forty-eight years (range, thirteen to seventy-eight years). Nineteen patients
      were treated with a single posterior plate, and eighteen were treated with a two
      plate construct with the plates parallel and lying at 90 degrees to each other.
      All of the nonunions were treated with bone-grafting, and an interfragmentary
      screw was used in thirty-six of the thirty-seven patients. Radiographs and the
      clinical status were evaluated at an average of thirteen months postoperatively.
      RESULTS: The biomechanical testing showed that the two-plate constructs were
      significantly stiffer than the single-plate constructs in all test modes (p <
      0.05). In the clinical part of the study, thirty-four (92%) of the nonunions
      healed without complications at an average of 4.8 months. Two nonunions treated
      with the two-plate construct and one treated with one plate failed to heal.
      CONCLUSIONS: No significant difference in the healing rate was found between the
      two clinical groups (p = 0.4, beta = 0.9), and the overall healing rate was 92%.
      However, a two-plate construct with the plates at right angles is mechanically
      stiffer than a single-plate construct, which might be helpful if rigid
      stabilization of the humerus at the midshaft level is needed.

PMID- 12177260
TI  - Early complications after one hundred and forty-four consecutive hip revisions
      with impacted morselized allograft bone and cement.
AB  - BACKGROUND: The use of impacted morselized allograft bone and cement in hip
      revision arthroplasty has been popular, but studies that specifically address
      intraoperative and postoperative complications have been scarce. METHODS: All
      complications that occurred during, and within the first year after, 144
      consecutive hip revision arthroplasties (108 stems and 130 sockets) performed
      with impacted morselized allograft bone and cement were recorded. Clinical and
      radiographic follow-up evaluation was performed at three months and at one year
      after surgery for all patients except eight (seven who had died of causes
      unrelated to the hip surgery and one who had sustained a stroke). Of these eight
      patients, seven had a six-week and/or three-month follow-up evaluation. RESULTS:
      Thirty-nine femoral fractures occurred in thirty-seven hips; twenty-nine of the
      fractures occurred during surgery and ten, within five months after surgery. Of
      the intraoperative femoral fractures, twelve were proximal, nine were diaphyseal,
      and eight involved the greater trochanter. Of the postoperative femoral
      fractures, one was proximal and nine were diaphyseal. Other intraoperative
      complications were the creation of a femoral cortical window in seven hips and
      incidental perforation of the femoral cortex in fourteen. Multivariate analysis
      showed the risk factors for femoral fracture during or after revision to be
      concomitant disease, greater deficiency of the femoral bone stock, and an
      intraoperative femoral window or perforation. Other complications included
      dislocation of the femoral head in nine hips, deep infection in one hip,
      persistence of preoperative deep infection in one hip, and superficial wound
      infection requiring wound debridement in two hips. CONCLUSIONS: We found the
      complication rate to be high after hip revision arthroplasty performed with
      impacted morselized allograft bone and cement. The most serious complication was
      postoperative diaphyseal femoral fracture.

PMID- 12177261
TI  - Development of flattening and apparent fragmentation following ischemic necrosis
      of the capital femoral epiphysis in a piglet model.
AB  - BACKGROUND: The repair response that follows ischemic necrosis of the immature
      femoral head and the biological processes that are responsible for the
      development of femoral head deformity and fragmentation have not been clearly
      defined. A piglet model was used to study the radiographic and histopathologic
      changes that occur prior to and during the development of femoral head deformity
      and fragmentation following ischemic necrosis. METHODS: Twenty-five male piglets
      were studied. A nonabsorbable ligature was placed tightly around the femoral neck
      to disrupt the blood supply to the capital femoral epiphysis. The animals were
      killed three days to eight weeks following the induction of ischemia. Radiographs
      of whole and sectioned femoral heads were made, and the radiographic findings
      were correlated with the histopathologic changes observed in the specimens.
      RESULTS: Mild femoral head flattening was observed by four weeks after the
      induction of ischemia, and severe flattening and fragmentation were observed by
      eight weeks. The predominant repair response observed following revascularization
      was osteoclastic bone resorption. Prior to the development of flattening, a large
      area of osteoclastic bone resorption was observed in the central region of the
      femoral head. Many osteoclasts were present along the revascularization front,
      which we believe were responsible for active resorption of the necrotic
      trabecular bone. Appositional new-bone formation, the hallmark of the repair
      response in adult ischemic necrosis, was not observed in the area of bone
      resorption. Instead, the areas of resorbed bone were replaced with a
      fibrovascular tissue that persisted for up to eight weeks. Appositional new-bone
      formation was observed, but it was limited to small areas in which
      revascularization was not followed by osteoclastic bone resorption and in which
      necrotic trabecular bone was still present. The simultaneous presence of the
      areas of bone resorption and new-bone formation contributed to the fragmented
      radiographic appearance of the femoral head. CONCLUSIONS: The predominant repair
      response observed in the piglet model of ischemic necrosis was osteoclastic bone
      resorption. The early bone loss, the lack of new-bone formation, and the
      persistence of fibrovascular tissue in the areas of bone resorption compromised
      the structural integrity of the femoral head and produced progressive femoral
      head flattening over time. The repair response was different from that observed
      in femoral heads removed from adult patients with ischemic necrosis and from that
      observed in the adult rabbit model of ischemic necrosis. CLINICAL RELEVANCE: The
      piglet model of ischemic necrosis may be useful for the investigation of the
      biological processes that lead to the development of femoral head deformity
      following ischemic necrosis of the immature femoral head.

PMID- 12177262
TI  - Conversion of a fused hip to total hip arthroplasty.
AB  - BACKGROUND: Arthrodesis of the hip remains a viable treatment for severe
      unilateral arthritis after traumatic injury or infection in a young but otherwise
      healthy individual. The goal of the present study was to review the long-term
      clinical and radiographic results after conversion of a fused hip to a total hip
      arthroplasty and to identify the risk factors that would lead to a higher rate of
      failure. METHODS: We performed a retrospective review of the charts and
      radiographs of 187 patients (208 hips) who had conversion of a fused hip to a
      total hip arthroplasty. The mean duration of follow-up after the conversion to
      total hip arthroplasty was 9.2 years (range, two to twenty-six years). RESULTS:
      The mean age at time of the arthroplasty was fifty-one years. The mean time
      interval between the arthrodesis and the conversion to a total hip arthroplasty
      was twenty-seven years. According to the information in the charts, at a mean
      duration of follow-up of 9.2 years after the total hip arthroplasty, 79% of hips
      were either pain-free or had minimal pain, 83% had good-to-excellent function,
      and 79% had good-to-excellent range of motion. Complications, which included
      fifteen nerve palsies, occurred in twenty-four hips. Twenty-eight hips had
      heterotopic ossification, but it was not associated with a recurrence of
      ankylosis or a marked reduction of motion. Revision arthroplasty was performed in
      twelve hips. The probability of survival of the implant was 96.1% (95% confidence
      interval, 91.5% to 98.2%) at ten years, 89.9% (95% confidence interval, 85.3% to
      96.1%) at fifteen years, and 72.8% (95% confidence interval, 36% to 90.6%) at
      twenty-six years. CONCLUSIONS: Conversion of a fused hip to a total hip
      arthroplasty has a favorable outcome. However, the technically demanding nature
      of the procedure should not be underestimated. Patients should be cautioned with
      regard to the possibility of a higher rate of complications than that seen with
      primary total hip arthroplasty.

PMID- 12177263
TI  - Improvement in the undertreatment of osteoporosis following hip fracture.
AB  - BACKGROUND: Osteoporosis is a common disease characterized by decreased bone mass
      and increased fracture risk in postmenopausal women and the elderly. Hip
      fractures are among the most common consequences of osteoporosis and
      unfortunately usually occur late in the course of the disease. When a patient is
      admitted to the hospital with a fragility hip fracture, a unique opportunity for
      diagnosis and treatment presents itself. Fortunately, several medications have
      proven to be effective in lowering the risk of future fractures. The purposes of
      the present study were to test the hypothesis that most fragility hip fractures
      go untreated and to determine whether educational efforts to raise physician
      awareness have led to an improvement in osteoporosis treatment rates. METHODS: A
      retrospective cohort study was performed with use of the patient databases at two
      university medical centers and one university-affiliated community hospital. The
      charts of 300 randomly selected patients were sorted with use of ICD-9
      (International Classification of Diseases, Ninth Revision) codes for femoral neck
      fractures. There were 100 patients from each center, with twenty-five patients
      from each year between 1997 and 2000. The admitting diagnosis, mechanism of
      injury, admission medications, procedures performed during hospitalization, and
      discharge medications were then extracted and analyzed. During this period, the
      National Osteoporosis Foundation established guiding principles for the treatment
      of fragility fractures. RESULTS: Of the seventy-five patients from all centers
      for each year from 1997 to 2000, 11%, 13%, 24%, and 29%, respectively, were
      discharged with a prescription for some medication targeting osteopenia, either
      supplemental calcium or an antiosteoporotic medication (estrogen, calcitonin, a
      bisphosphonate, or raloxifene). A trended chi-square analysis of this increase
      revealed a p value of <0.001, indicating that this improvement in treatment was
      unlikely due to chance alone. Fifty-eight (19.3%) of the 300 patients in the
      study received a prescription at the time of discharge. However, forty of these
      patients (13.3% of the overall group) received calcium and only eighteen (6.0% of
      the overall group) received a medication to actively prevent bone resorption and
      treat osteoporosis. In addition, no patient underwent a bone density scan while
      in the hospital. CONCLUSIONS: Elderly patients and postmenopausal women who are
      admitted to the hospital and diagnosed with a low-energy femoral neck fracture
      have been undertreated for osteoporosis. However, over the four years of the
      present study, there was a significant increase in the rate of treatment. It is
      hoped that treatment rates will continue to increase in the future with continued
      educational efforts.

PMID- 12177264
TI  - Characterizing the functional improvement after total shoulder arthroplasty for
      osteoarthritis.
AB  - BACKGROUND: Both shoulder surgeons and patients who are considering total
      shoulder arthroplasty are interested in the anticipated improvement in shoulder
      comfort and function after the procedure. The purpose of the present study was to
      characterize shoulder-specific functional gains in relation to preoperative
      shoulder function and to present this information in a way that can be easily
      communicated to patients who are considering this surgery. METHODS: We analyzed
      the preoperative and follow-up shoulder function in patients managed with total
      shoulder arthroplasty for the treatment of primary glenohumeral osteoarthritis.
      Functional self-assessments were available for 102 (80%) of 128 shoulders after
      thirty to sixty months of follow-up. Outcome was assessed with respect to the
      change in the number of shoulder functions that were performable, the change in
      shoulder function as a percentage of the preoperative functional deficit, and the
      change in the ability to perform specific shoulder functions. RESULTS: The
      average number of shoulder functions that were performable improved from four of
      twelve preoperatively to nine of twelve postoperatively (p < 0.01). Function
      improved in ninety-six shoulders (94%). The number of functions that were
      performable at the time of follow-up was positively associated with preoperative
      shoulder function (p < 0.05): the better the preoperative function, the better
      the follow-up function. The improvement in function was greatest for shoulders
      with less preoperative function (p < 0.01). On the average, patients regained
      approximately two-thirds of the functions that had been absent preoperatively.
      Significant improvement was noted in eleven of the twelve shoulder functions that
      were examined (p < 0.01). The chance of regaining a function that had been absent
      before surgery was 73%, whereas the chance of losing a function that had been
      present before surgery was 6%. Older men tended to have greater functional
      improvement than younger men. CONCLUSION: Total shoulder arthroplasty for the
      treatment of primary glenohumeral osteoarthritis significantly improves shoulder
      function. Postoperative function is related to preoperative function. The
      improvement that was observed in this clinical series can be conveyed to patients
      most simply by stating that, after surgery, shoulders typically regained
      approximately two-thirds of the functions that had been absent preoperatively.

PMID- 12177265
TI  - Reconstruction of a ruptured patellar tendon with achilles tendon allograft
      following total knee arthroplasty.
AB  - BACKGROUND: Rupture of the patellar tendon after total knee arthroplasty is a
      rare and debilitating complication. Proper surgical management of this condition
      remains controversial. The purpose of this study was to review the results of
      reconstruction of a ruptured patellar tendon with an Achilles tendon allograft
      following total knee arthroplasty. METHODS: We reviewed our experience with the
      use of a fresh-frozen Achilles tendon allograft with an attached calcaneal bone
      graft to restore extensor function in nine patients with patellar tendon rupture
      following total knee arthroplasty (five primary and four revision). All patients
      were examined clinically and radiographically at an average of twenty-eight
      months. RESULTS: The average knee and functional scores improved from 26 and 14
      points, respectively, before the surgery to 81 and 53 points after the surgery.
      The average extensor lag decreased from 44 degrees preoperatively to 3 degrees
      postoperatively, and the average range of motion of the knee increased from 88
      degrees to 107 degrees. Two grafts failed in the early postoperative period. Both
      were repaired successfully. Radiographs showed an average proximal patellar
      migration of 17.8 mm, which did not appear to affect extensor function.
      CONCLUSIONS: This short-term follow-up study showed that once an Achilles
      allograft has healed, it can serve as a reliable reconstruction of a ruptured
      patellar tendon following total knee arthroplasty. This technique may be
      particularly suited for patients in whom the extensor mechanism was compromised
      by multiple prior operations. Continued follow-up is necessary to determine the
      long-term durability of these results.

PMID- 12177266
TI  - Osteolysis associated with a cemented modular posterior-cruciate-substituting
      total knee design : five to eight-year follow-up.
AB  - BACKGROUND: Most intermediate and long-term studies of cemented posterior
      cruciate-substituting total knee prostheses were performed with nonmodular tibial
      components. The purpose of this study was to evaluate the intermediate-term
      results of posterior-cruciate-substituting total knee arthroplasties in which a
      cemented modular tibial component had been used, with a particular focus on
      evaluating the prevalence of radiographic osteolysis. METHODS: Between 1992 and
      1995, 176 consecutive primary total knee arthroplasties with use of the Insall
      Burstein II system were performed in 134 patients at our institution. A modular
      metal-backed tibial component was inserted in 145 knees, and an all-polyethylene
      tibial component of the same design was inserted in thirty-one. Standard
      terminology questionnaires were completed or Knee Society and The Hospital for
      Special Surgery scores were determined preoperatively and at the time of final
      follow-up, at an average of 6.4 years (range, 5.0 to 7.9 years). Initial
      postoperative radiographs were compared with those made at the time of final
      follow-up to assess component position, wear, radiolucent lines, and osteolysis.
      RESULTS: Ninety-two patients (128 knees) treated with the modular tibial
      component were alive at the time of final follow-up. No patient was lost to
      follow-up. Radiographs were available for 105 knees (82%). Three knees had been
      revised because of instability or infection; none had been revised because of
      loosening or osteolysis. The mean Knee Society clinical and functional scores
      were 85 points (range, 41 to 100 points) and 79 points (range, 30 to 100 points),
      respectively, at the time of final follow-up. According to The Hospital for
      Special Surgery score, 94% of the knees had a good or excellent result. Knee
      flexion averaged 113 degrees (range, 90 degrees to 130 degrees ) at the time of
      final follow-up. Osteolysis was present in seventeen (16%) of the knees with
      radiographic follow-up. Osteolysis did not develop in any knee in which an all
      polyethylene tibial component had been used. Two knees (in one patient) were
      revised because of osteolytic lesions found at the time of follow-up for the
      study. Both of these knees had anterior wear of the tibial post due to
      impingement and backside tibial polyethylene wear. CONCLUSIONS: Modular Insall
      Burstein II total knee prostheses were found to function well after five to eight
      years of follow-up. However, the high prevalence of osteolysis in patients who
      had good or excellent clinical scores is worrisome. Particular attention should
      be paid to preventing flexion of the femoral component, posterior slope of the
      tibial component, or hyperextension of the knee when posterior-cruciate
      substituting total knee arthroplasty is performed. We also recommend routine
      follow-up radiographs after all total joint arthroplasties to detect asymptomatic
      osteolytic changes.

PMID- 12177268
TI  - Double level osteotomy of the knee: a method to retain joint-line obliquity.
      Clinical results.
AB  - BACKGROUND: Although general guidelines have been proposed for proximal tibial
      and supracondylar osteotomies, double level osteotomy provides the advantage of
      maintaining neutral joint-line obliquity in addition to correcting limb
      malalignment around the knee. The goal of this prospective study was to determine
      the outcome of double level osteotomy of the knee performed after analysis with
      computer-aided preoperative planning software in patients with varus
      malalignment. METHODS: Twenty-nine double level osteotomies of the knee were
      performed in twenty-four patients. The patients were followed for an average
      duration of 82.7 months (range, twenty-seven to 137 months). All knees had
      moderate-to-severe varus deformity and arthritis. The mean preoperative
      mechanical tibiofemoral angle was 193.9 degrees (that is, 13.9 degrees of varus).
      Preoperative and postoperative evaluations included clinical (scores according to
      the Knee Society system), radiographic, and computer-aided analysis of the
      mechanical status of the knee joint. Failure was defined as conversion of an
      osteotomy to a total knee arthroplasty or the presence of severe pain in a
      patient who declined arthroplasty. RESULTS: The mean clinical and functional
      scores according to the Knee Society system improved from 34 and 64 points,
      respectively, before the osteotomy to 90 (p < 0.0001) and 81 points (p = 0.079)
      at the time of the final follow-up examination. One patient was lost to follow
      up. One of the twenty-nine knees was subsequently converted to total knee
      arthroplasty forty-nine months postoperatively. The cumulative rate of survival
      at 100 months was 96% (95% confidence interval, +4.5 to -8.7), with eight
      patients remaining at risk. CONCLUSIONS: Double osteotomy is a valuable procedure
      for patients with such a large varus deformity that appropriate realignment and
      load transfer to the unaffected compartment, together with an acceptable joint
      line obliquity, cannot be achieved by a single osteotomy.

PMID- 12177267
TI  - Prevalence of fat embolism following bilateral simultaneous and unilateral total
      hip arthroplasty performed with or without cement : a prospective, randomized
      clinical study.
AB  - BACKGROUND: Controversy exists regarding the safety of bilateral simultaneous
      total hip arthroplasty, in part because of the potentially higher prevalence of
      pulmonary fat embolism. The purpose of the present study was to determine if
      unilateral and bilateral simultaneous total hip arthroplasty procedures resulted
      in different prevalences of fat embolization, different degrees of hemodynamic
      compromise, or different levels of hypoxemia or mental status changes. METHODS:
      One hundred and fifty-six consecutive patients undergoing primary total hip
      arthroplasty were prospectively enrolled in the study. The study group included
      fifty patients undergoing bilateral simultaneous total hip arthroplasty and 106
      patients undergoing unilateral total hip arthroplasty. One hundred hips were
      treated with a cemented stem, and 106 were treated with a cementless stem.
      Arterial and right atrial blood samples were obtained before implantation
      (baseline); at one, three, five, and ten minutes after implantation of the
      acetabular and femoral components; and at twenty-four and forty-eight hours after
      the operation. Arterial blood pressure, right atrial pressure, arterial oxygen
      tension, and carbon-dioxide tension were also monitored at these times. The
      presence of lipid and cellular contents of bone marrow was determined. RESULTS:
      The prevalence of fat embolism was not significantly different between the groups
      managed with bilateral and unilateral total hip arthroplasty or between the
      groups managed with cemented and cementless stems. Similarly, the prevalence of
      bone-marrow-cell embolization was not significantly different between the groups
      managed with bilateral and unilateral total hip arthroplasty or between the
      groups managed with cemented and cementless stems. Patients with bone-marrow-cell
      embolization had a significantly lower arterial oxygen tension (p = 0.022) and
      oxygen saturation (p = 0.017) than did patients without bone-marrow-cell
      embolization on the first postoperative day. Four patients with bone-marrow cells
      in the blood samples that were obtained from the right atrium on the first
      postoperative day had development of diffuse encephalopathy with confusion and
      agitation that lasted for about twenty-four hours. CONCLUSIONS: The prevalence of
      fat and bone-marrow-cell embolization was similar in the groups managed with
      bilateral simultaneous and unilateral total hip arthroplasty as well as in the
      groups managed with cemented and cementless stems.

PMID- 12177269
TI  - Clinical and radiographic predictors of scoliosis in patients with
      myelomeningocele.
AB  - BACKGROUND: The prevalence of scoliosis in patients with myelomeningocele has
      been reported to be as high as 80% to 90% in some studies. However, those studies
      included patients with both congenital and developmental curves. The variation in
      the patient population as well as the definition of scoliosis in those studies
      made it difficult to predict the true prevalence of scoliosis in these patients.
      The purpose of the present study was to identify clinical and radiographic
      factors that may predict the onset of developmental scoliosis in patients with
      myelomeningocele. METHODS: A retrospective review of the charts and radiographs
      of all patients with a diagnosis of myelomeningocele who were seen in our clinic
      between 1990 and 1995 was performed. The criteria for inclusion in the study
      included a diagnosis of myelomeningocele or lipomeningocele, an age of more than
      ten years at the time of the review, serial documentation of motor power, and
      radiographic documentation of spinal deformity primarily in the coronal plane.
      The radiographs were examined to assess the degree of scoliosis and to document
      the last intact laminar arch. The relationship between the degree of scoliosis
      and the last intact laminar arch was evaluated. Statistical analysis was
      performed to assess the association between scoliosis and the clinical motor
      level, the ambulatory status, spasticity, motor asymmetry, and hip instability.
      RESULTS: One hundred and forty-one patients satisfied the criteria for inclusion
      in the study. Seventy-four patients (52%) had scoliosis. The average duration of
      follow-up was 9.4 years (range, three to thirty years), and the average age of
      the patients was nineteen years (range, ten to forty-two years). Scoliosis
      developed before the age of nine years in forty-three patients and after the age
      of nine years in thirty-one patients, with new curves continuing to develop until
      the age of fifteen years. Curves of <20 degrees degrees often resolved. The
      clinical motor level, ambulatory status, and last intact laminar arch were all
      found to be predictive factors for the development of scoliosis in these
      patients. CONCLUSIONS: In the population of patients with myelomeningocele, the
      term scoliosis should be reserved for curves of >20 degrees. New curves may
      continue to develop until the age of fifteen years. The level of the last intact
      laminar arch is a useful early predictor of the development of scoliosis in these
      patients.

PMID- 12177270
TI  - Structural changes in the forefoot of individuals with diabetes and a prior
      plantar ulcer.
AB  - BACKGROUND: Plantar ulcers produced by diabetic foot disease are devastating and
      costly. Better understanding of the ulcer-producing process is important to
      improve detection of feet that are at risk and to improve intervention. We
      identified and quantified soft-tissue and osseous structural changes in the
      forefoot of diabetic patients with a prior plantar ulcer. METHODS: Thirty-two
      individuals with a mean age (and standard deviation) of 57 +/- 11 years were
      studied; sixteen had diabetes (of a mean of 20 +/- 11 years' duration),
      peripheral neuropathy, and a prior plantar ulcer, and sixteen were matched
      controls. Computed tomography was used to evaluate forefoot structure, including
      the plantar soft-tissue (muscle) density, soft-tissue thickness beneath the
      metatarsal heads, metatarsophalangeal joint angle, metatarsal bone density, and
      metatarsophalangeal joint arthropathy. RESULTS: Plantar soft-tissue (muscle)
      density was lower in the individuals with diabetes (mean, 1 HU [Hounsfield unit])
      than it was in the controls (mean, 18 HU). There was no difference in the soft
      tissue thickness beneath the metatarsal heads (mean, 10 mm) between the
      individuals with diabetes and the controls, but the soft-tissue thickness
      decreased with age. The individuals with diabetes had greater extension deformity
      of the first, second, and third metatarsophalangeal joints and greater
      arthropathy of the second, third, and fourth metatarsophalangeal joints. There
      were no significant differences in metatarsal bone density between the groups.
      CONCLUSIONS: There were significant differences between the forefeet of
      individuals with diabetes and a previous plantar ulcer and those of controls:
      plantar muscle density was decreased, and metatarsophalangeal joint extension and
      arthropathy were increased. Interestingly, the soft-tissue thickness under the
      metatarsal heads in the controls was not greater than that in the diabetic
      patients. CLINICAL RELEVANCE: This study demonstrated structural differences
      between the forefeet of patients with diabetes and a previous ulcer and those of
      normal age-matched controls. The information can serve to guide new interventions
      to prevent or treat foot ulcerations in this patient population.

PMID- 12177271
TI  - Recombinant adeno-associated virus-mediated osteoprotegerin gene therapy inhibits
      wear debris-induced osteolysis.
AB  - BACKGROUND: Aseptic loosening of orthopaedic implants secondary to wear debris
      induced osteolysis is a serious problem. Osteoprotegerin (OPG) is a natural decoy
      protein that inhibits osteoclast activation and bone resorption. This study
      investigated whether gene therapy using a recombinant adeno-associated viral
      vector that expresses OPG can inhibit wear debris-induced osteolysis. METHODS: A
      recombinant adeno-associated virus (rAAV) vector co-expressing OPG (rAAV-OPG-IRES
      EGFP) was generated. A control vector expressing b-galactosidase (rAAV-LacZ) was
      also prepared. In vitro validation experiments were performed to determine rAAV
      OPG-IRES-EGFP transduction efficiency, OPG expression level and function in bone
      wafer, and osteoclastic activity. The effect of rAAV-OPG-IRES-EGFP in vivo gene
      therapy on wear debris-induced osteolysis was then evaluated in a mouse calvarial
      model in which a single intramuscular injection of the vector was administered
      prior to the introduction of the wear debris. The effects of the rAAV-OPG-IRES
      EGFP gene therapy on wear debris-induced osteoclastogenesis and bone resorption
      were determined by histomorphometry on day 10. RESULTS: In vitro experiments
      revealed that 100% of human embryonic kidney 293 cells were transduced at a
      multiplicity of infection of 1000 with both rAAV-OPG-IRES-EGFP and rAAV-LacZ. At
      a rAAV-OPG-IRES-EGFP multiplicity of infection of 1000, an OPG concentration of
      135 ng/mL of culture media was achieved after four days. Using a bone-wafer assay
      for osteoclast activity, we found that treatment with rAAV-OPG-IRES-EGFP reduced
      resorption sevenfold compared with parathyroid hormone-stimulated controls and
      elevenfold compared with rAAV-LacZ controls. Furthermore, a seventeenfold
      decrease in RANKL and macrophage colony-stimulating factor-induced splenocyte
      osteoclastogenesis was observed in co-cultures containing rAAV-OPG-IRES-EGFP
      infected fibroblasts. In vivo administration of rAAV-OPG-IRES-EGFP resulted in
      detectable transduction of myocytes at the injection site and a significant
      increase in expression of serum OPG levels by the second day (p < 0.05). Maximal
      concentrations were obtained on day 6 and then leveled off throughout the
      observation period. In contrast, serum OPG could not be detected in the sham
      treated, uninfected titanium-stimulated, or rAAV-LacZ-infected mice. In the
      control mice, titanium implantation resulted in a threefold increase in the mean
      number of osteoclasts adjacent to the sagittal suture as well as a twofold
      increase in the mean area of soft tissue in the sagittal suture compared with the
      sham-treated mice. In contrast, osteoclast numbers remained at basal levels, and
      the area of soft tissue in the sagittal suture was markedly reduced in titanium
      implanted animals that received rAAV-OPG-IRES-EGFP treatment, demonstrating a
      complete inhibition of osteolysis in response to titanium particles. CONCLUSIONS:
      A single intramuscular injection of the rAAV-OPG-IRES-EGFP vector can efficiently
      transduce myocytes to produce high levels of OPG. The OPG effectively inhibits
      wear debris-induced osteoclastogenesis and osteolysis. CLINICAL RELEVANCE:
      Currently, there is no approved drug therapy to prevent or inhibit periprosthetic
      osteolysis. Although preclinical studies have identified potential drug therapies
      (i.e., bisphosphonates), there is no evidence that these drugs can effectively
      treat aseptic loosening in patients. This is the first evidence that in vivo OPG
      gene therapy can be used to prevent wear debris-induced osteolysis.

PMID- 12177272
TI  - Cubital tunnel syndrome associated with medial elbow Ganglia and osteoarthritis
      of the elbow.
AB  - BACKGROUND: Medial elbow ganglia have been reported in association with cubital
      tunnel syndrome. This lesion is thought to occur rarely and has not been
      emphasized in the literature. The purposes of the present study are to report our
      experience with this lesion in order to elucidate its prevalence as well as its
      clinical and radiographic features, to describe our operative findings, and to
      present the results of surgical treatment. METHODS: Four hundred and eighty-seven
      elbows in 472 patients were treated for cubital tunnel syndrome between 1980 and
      1999. We performed a retrospective study of the thirty-eight patients who had a
      medial ganglion. All of the ganglia were excised, and the ulnar nerve was
      translocated subcutaneously. Thirty-two patients were followed for a mean of
      thirty-seven months. RESULTS: Medial elbow ganglion was the third most common
      causative factor associated with cubital tunnel syndrome, with an overall
      prevalence of 8%. Resting pain in the medial aspect of the elbow was reported by
      twenty-five of the thirty-eight patients, and a sudden onset of numbness in the
      ring and little fingers or of medial elbow pain without prior symptoms was
      reported by twenty-nine patients. The symptoms lasted two months or less in
      thirty-one patients. All ganglia originated from the medial aspect of the
      ulnohumeral joint, and radiographs of that joint showed degenerative changes in
      thirty-seven patients. At the time of follow-up, all measurements of sensory and
      motor function of the ulnar nerve had improved and no recurrence of nerve palsy
      was found. CONCLUSIONS: Although uncommon, medial elbow ganglia have a strong
      association with osteoarthritis of the elbow and can cause a relatively acute
      onset of cubital tunnel syndrome. A patient with cubital tunnel syndrome
      associated with elbow osteoarthritis who complains of medial elbow pain or severe
      numbness within two months after the onset of the syndrome should be strongly
      suspected of having a ganglion. Most ganglia are occult, and ultrasonography and
      magnetic resonance imaging can assist in the preoperative diagnosis. Careful
      excision of the ganglion performed concurrently with subcutaneous anterior
      transposition of the ulnar nerve can produce satisfactory results.

PMID- 12177273
TI  - Cryopreservation of osteochondral allografts: dimethyl sulfoxide promotes
      angiogenesis and immune tolerance in mice.
AB  - BACKGROUND: Although transplantation of cryopreserved bone allografts has become
      a routine procedure in orthopaedic surgery, biological and immunological
      impairment remains an unsolved problem that causes clinical failures.
      Experimental and clinical evidence has indicated that bone grafts that are
      revascularized early remain viable and contribute to union at the recipient site.
      Unprotected cryopreservation, used in most bone banks to reduce graft
      antigenicity, is associated with complete loss of graft viability, potentially
      contributing to graft failure. The differences in the survival of various cell
      types during cryopreservation with use of dimethyl sulfoxide, particularly the
      increased sensitivity of leukocytes to fast freezing, has resulted in a new
      approach to modulate immunogenicity. On the basis of this concept, it was
      proposed that a reduction in the immune response and enhanced revascularization
      of osteochondral allografts could be achieved by rapid cryopreservation with
      dimethyl sulfoxide. To test this hypothesis, angiogenesis and immune tolerance
      were quantified in a murine model with use of intravital microscopy. METHODS:
      Fresh osteochondral tissue and osteochondral tissue that had been cryopreserved
      with and without dimethyl sulfoxide was transplanted into dorsal skinfold
      chambers as isografts and as allografts in presensitized and nonsensitized
      recipient mice. To quantify angiogenesis, the onset of hemorrhages in the
      vicinity of the grafts and the revascularization of the grafts were determined by
      means of intravital fluorescence microscopy. To determine the recipient's
      intravascular immune response to the grafts, the leukocyte-endothelium
      interaction was assessed on the twelfth day after transplantation. RESULTS: Nine
      of nine fresh isografts were revascularized at a mean (and standard deviation) of
      57 +/- 33 hours, eight of nine isografts that had been cryopreserved with
      dimethyl sulfoxide were revascularized at 98 +/- 50 hours, and zero of nine
      isografts that had been cryopreserved without dimethyl sulfoxide were
      revascularized. Seven of seven fresh allografts were revascularized at 53 +/- 6
      hours, and ten of ten allografts that had been cryopreserved with dimethyl
      sulfoxide were revascularized at 82 +/- 29 hours. However, signs of
      revascularization faded in four of the seven fresh allografts whereas reperfusion
      was maintained in the majority (seven) of the ten grafts frozen in the presence
      of dimethyl sulfoxide. Similar to the findings associated with unprotected frozen
      isografts, zero of ten unprotected frozen allografts were revascularized. None of
      the allografts that had been transplanted into presensitized recipients were
      revascularized, regardless of whether they had been implanted fresh (nine grafts)
      or had been implanted after protected (eight grafts) or unprotected (nine grafts)
      freezing. Quantification of the leukocyte-endothelium interaction revealed a
      reduction in the intravascular immune response to frozen allografts (both
      protected and unprotected) compared with fresh allografts. CONCLUSION:
      Osteochondral allografts that had been pretreated by cryopreservation with
      dimethyl sulfoxide demonstrated improved angiogenesis induction and enhanced
      immune tolerance compared with unprotected frozen grafts. A selective reduction
      in donor passenger leukocytes is the proposed mechanism underlying this
      phenomenon. CLINICAL RELEVANCE: In the absence of presensitization,
      cryopreservation with dimethyl sulfoxide appears to reduce the immune response to
      allografts and to enhance their revascularization; in the presence of
      presensitization, alternatives to allograft transplantation should be considered
      since the allografts will be exposed to a deleterious immune response.

PMID- 12177274
TI  - Aortic dissection presenting as an acute cauda equina syndrome : a case report.

PMID- 12177275
TI  - Observations on a retrieved patellar tendon autograft used to reconstruct the
      anterior cruciate ligament. A case report.

PMID- 12177276
TI  - Extensive periacetabular osteolysis presenting as a mass on rectal examination. A
      case report.

PMID- 12177277
TI  - Idiopathic heterotopic ossification within the tibial nerve. A case report.

PMID- 12177280
TI  - Toward better interaction between orthopaedists and researchers: a two-way
      street.

PMID- 12177279
TI  - The estimated costs of manuscripts associated with OREF funding.

PMID- 12177281
TI  - Congenital dislocation of the hip: use of the Pavlik harness in the child during
      the first six months of life. 1976.

PMID- 12177282
TI  - Appropriate pain management in orthopaedic trauma care.

PMID- 12177283
TI  - The pros and cons of modularity in total knee replacements.

PMID- 12177284
TI  - Minimally invasive techniques for total hip arthroplasty.

PMID- 12177286
TI  - Physiotherapy or a wait-and-see policy were best long-term treatment options for
      lateral epicondylitis.

PMID- 12177285
TI  - The relationship of surgical volume to quality of care: scientific considerations
      and policy implications.

PMID- 12177288
TI  - The pertrochanteric external fixator reduced pain, hospital stay, and mechanical
      complications in comparison with the sliding hip screw.

PMID- 12177290
TI  - Open carpal tunnel release is the preferred method of surgical treatment for
      carpal tunnel syndrome.

PMID- 12177292
TI  - What's new in orthopaedic research.

PMID- 12177293
TI  - The non-Watson-Crick base pairs and their associated isostericity matrices.
AB  - RNA molecules exhibit complex structures in which a large fraction of the bases
      engage in non-Watson-Crick base pairing, forming motifs that mediate long-range
      RNA-RNA interactions and create binding sites for proteins and small molecule
      ligands. The rapidly growing number of three-dimensional RNA structures at atomic
      resolution requires that databases contain the annotation of such base pairs. An
      unambiguous and descriptive nomenclature was proposed recently in which RNA base
      pairs were classified by the base edges participating in the interaction (Watson
      Crick, Hoogsteen/CH or sugar edge) and the orientation of the glycosidic bonds
      relative to the hydrogen bonds (cis or trans). Twelve basic geometric families
      were identified and all 12 have been observed in crystal structures. For each
      base pairing family, we present here the 4 x 4 'isostericity matrices'
      summarizing the geometric relationships between the 16 pairwise combinations of
      the four standard bases, A, C, G and U. Whenever available, a representative
      example of each observed base pair from X-ray crystal structures (3.0 A
      resolution or better) is provided or, otherwise, theoretically plausible models.
      This format makes apparent the recurrent geometric patterns that are observed and
      helps identify isosteric pairs that co-vary or interchange in sequences of
      homologous molecules while maintaining conserved three-dimensional motifs.

PMID- 12177295
TI  - Transcription and nuclear transport of CAG/CTG trinucleotide repeats in yeast.
AB  - Trinucleotide repeats are involved in several neurological disorders in humans.
      DNA sequences containing CAG/CTG repeats are prone to slippage during replication
      and double-strand break repair. The effects of trinucleotide repeats on
      transcription and on nuclear export were analyzed in vivo in yeast. Transcription
      of a CAG/CTG trinucleotide repeat in the 3'-untranslated region of a URA3
      reporter gene leads to transcription of messenger RNAs several kilobases longer
      than the expected size. These long mRNAs form more readily when CAG rather than
      CTG repeats are transcribed. CAG- or CUG-containing transcripts show a non
      homogeneous cellular localization. We propose that long mRNAs result from
      transcription slippage, and discuss the possible implications for human diseases.

PMID- 12177294
TI  - Transcription elongation factor Spt4 mediates loss of phosphorylated RNA
      polymerase II transcription in response to DNA damage.
AB  - Previously, we found that Rad26, the yeast Cockayne syndrome B homolog and the
      transcription elongation factor Spt4 mediate transcription-coupled repair of UV
      induced DNA damage. Here we studied the effect of DNA damage on transcription by
      directly analyzing the RNA polymerase II localization at active genes in vivo. A
      rad26 defect leads to loss of Ser5 phosphorylated RNA polymerase II localization
      to active genes, while localization is only transiently diminished in wild type
      cells. In contrast, loss of Ser5-P RNAP II localization is suppressed in spt4
      cells. Interestingly, even when DNA damage is persistent the absence of Spt4
      leads to a delayed loss of transcription suggesting that Spt4 is directly
      involved in mediating transcription shutdown. Comparative analysis of
      phosphorylated and non-phosphorylated RNA polymerase II localization revealed
      that Ser5-P RNAP II is preferentially lost in the presence of DNA damage. In
      addition, we found evidence for a transient Rad26 localization to active genes in
      response to DNA damage. These findings provide insight into the transcriptional
      response to DNA damage and the factors involved in communicating this response,
      which has direct implications for our understanding of transcription-repair
      coupling.

PMID- 12177296
TI  - A splicing silencer that regulates smooth muscle specific alternative splicing is
      active in multiple cell types.
AB  - Alternative splicing of alpha-tropomyosin (alpha-TM) involves mutually exclusive
      selection of exons 2 and 3. Selection of exon 2 in smooth muscle (SM) cells is
      due to inhibition of exon 3, which requires both binding sites for polypyrimidine
      tract-binding protein as well as UGC (or CUG) repeat elements on both sides of
      exon 3. Point mutations or substitutions of the UGC-containing upstream
      regulatory element (URE) with other UGC elements disrupted the alpha-TM splicing
      pattern in transfected cells. Multimerisation of the URE caused enhanced exon
      skipping in SM and various non-SM cells. In the presence of multiple UREs the
      degree of splicing regulation was decreased due to the high levels of exon
      skipping in non-SM cell lines. These results suggest that the URE is not an
      intrinsically SM- specific element, but that its functional strength is fine
      tuned to exploit differences in the activities of regulatory factors between SM
      and other cell types. Co-transfection of tropomyosin reporters with members of
      the CUG-binding protein family, which are candidate URE-binding proteins,
      indicated that these factors do not mediate repression of tropomyosin exon 3.

PMID- 12177297
TI  - C.EcoO109I, a regulatory protein for production of EcoO109I restriction
      endonuclease, specifically binds to and bends DNA upstream of its translational
      start site.
AB  - The EcoO109I restriction-modification system, which recognizes 5'-(A/G)GGNCC(C/T)
      3', has been cloned, and contains convergently transcribed endonuclease and
      methylase. The role and action mechanism of the gene product, C.EcoO109I, of a
      small open reading frame located upstream of ecoO109IR were investigated in vivo
      and in vitro. The results of deletion analysis suggested that C.EcoO109I acts as
      a positive regulator of ecoO109IR expression but has little effect on ecoO109IM
      expression. Assaying of promoter activity showed that the expression of ecoO109IC
      was regulated by its own gene product, C.EcoO109I. C.EcoO109I was overproduced as
      a His-tag fusion protein in recombinant Escherichia coli HB101 and purified to
      homogeneity. C.EcoO109I exists as a homodimer, and recognizes and binds to the
      DNA sequence 5'-CTAAG(N)(5)CTTAG-3' upstream of the ecoO109IC translational start
      site. It was also shown that C.EcoO109I bent the target DNA by 54 +/- 4 degrees.

PMID- 12177298
TI  - Oxidative DNA damage induced by copper and hydrogen peroxide promotes CG-->TT
      tandem mutations at methylated CpG dinucleotides in nucleotide excision repair
      deficient cells.
AB  - Oxidative DNA damage may play an important role in human disease including
      cancer. Previously, mutational spectra have been determined using systems that
      include transition metal ions and hydrogen peroxide (H2O2). G-->T transversions
      and C-->T transitions were the most common mutations observed including some CC-
      >TT tandem mutations. C-->T transition mutations at methylated CpG dinucleotides
      are the most common mutations in human genetic diseases. It has been hypothesized
      that oxidative stress may increase the frequency of mutations at methylated CpG
      sequences. Here we have used a CpG-methylated shuttle vector to derive mutational
      spectra of copper/H2O2-induced DNA damage upon passage of the shuttle vector
      through human fibroblasts. We find that copper/H2O2 treatment produces higher
      numbers of CpG transition mutations when the CpGs are methylated but does not
      create clear C-->T hotspots at these sites. More strikingly, we observed that
      this treatment produces a substantial frequency of mutations that were mCG-->TT
      tandem mutations. Six of seven tandem mutations were of this type. mCG-->TT
      mutations (6/63 = 10% of all mutations) were observed only in nucleotide excision
      repair-deficient (XP-A) cells but were not found in repair-proficient cells. The
      data suggest that this novel type of mutation may be produced by vicinal or cross
      linked base damage involving 5-methylcytosine and a neighboring guanine, which is
      repaired by nucleotide excision repair. We suggest that the underlying oxidative
      lesions could be responsible for the progressive neurodegeneration seen in XP-A
      individuals.

PMID- 12177299
TI  - RNA molecules with structure dependent functions are uniquely folded.
AB  - Cis-acting elements in post-transcriptional regulation of gene expression are
      often correlated with distinct local RNA secondary structure. These structures
      are expected to be significantly more ordered than those anticipated at random
      because of evolutionary constraints and intrinsic structural properties. In this
      study, we introduce a computing method to calculate two quantitative measures,
      NRd and Stscr, for estimating the uniqueness of an RNA secondary structure. NRd
      is a normalized score based on evaluating how different a natural RNA structure
      is from those predicted for its randomly shuffled variants. The lower the score
      NRd the more well ordered is the natural RNA structure. The statistical
      significance of NRd compared with that computed from structural comparisons among
      large numbers of randomly permuted sequences is represented by a standardized
      score, STSCR: We tested the method on the trans-activation response element and
      Rev response element of HIV-1 mRNA, internal ribosome entry sequence of hepatitis
      C virus, Tetrahymena thermophila rRNA intron, 100 tRNAs and 14 RNase P RNAs. Our
      data indicate that functional RNA structures have high Stscr, while other
      structures have low Stscr. We conclude that RNA functional molecules and/or cis
      acting elements with structure dependent functions possess well ordered
      conformations and they are uniquely folded as measured by this technique.

PMID- 12177300
TI  - Ku heterodimer binds to both ends of the Werner protein and functional
      interaction occurs at the Werner N-terminus.
AB  - The human Werner syndrome protein, WRN, is a member of the RecQ helicase family
      and contains 3'-->5' helicase and 3'-->5' exonuclease activities. Recently, we
      showed that the exonuclease activity of WRN is greatly stimulated by the human Ku
      heterodimer protein. We have now mapped this interaction physically and
      functionally. The Ku70 subunit specifically interacts with the N-terminus (amino
      acids 1-368) of WRN, while the Ku80 subunit interacts with its C-terminus (amino
      acids 940- 1432). Binding between Ku70 and the N-terminus of WRN (amino acids 1
      368) is sufficient for stimulation of WRN exonuclease activity. A mutant Ku
      heterodimer of full-length Ku80 and truncated Ku70 (amino acids 430-542)
      interacts with C-WRN but not with N-WRN and cannot stimulate WRN exonuclease
      activity. This emphasizes the functional significance of the interaction between
      the N-terminus of WRN and Ku70. The interaction between Ku80 and the C-terminus
      of WRN may modulate some other, as yet unknown, function. The strong interaction
      between Ku and WRN suggests that these two proteins function together in one or
      more pathways of DNA metabolism.

PMID- 12177301
TI  - Metallo-beta-lactamase fold within nucleic acids processing enzymes: the beta
      CASP family.
AB  - A separate family of enzymes within the metallo-beta-lactamase fold comprises
      several important proteins acting on nucleic acid substrates, involved in DNA
      repair (Artemis, SNM1 and PSO2) and RNA processing [cleavage and polyadenylation
      specificity factor (CPSF) subunit]. Proteins of this family, named beta-CASP
      after the names of its representative members, possess specific features relative
      to those of other metallo-beta-lactamases, that are concentrated in the C
      terminal part of the domain. In this study, using sensitive methods of sequence
      analysis, we identified highly conserved amino acids specific to the beta-CASP
      family, some of which were unidentified to date, that are predicted to play
      critical roles in the enzymatic function. The identification and characterisation
      of all the extant, detectable beta-CASP members within sequence databases and
      genome data also allowed us to unravel particular sequence features which are
      likely to be involved in substrate specificity, as well as to describe new but as
      yet uncharacterised members which may play critical roles in DNA and RNA
      metabolism.

PMID- 12177302
TI  - Imprinting regulator DNMT3L is a transcriptional repressor associated with
      histone deacetylase activity.
AB  - DNMT3L is a regulator of imprint establishment of normally methylated maternal
      genomic sequences. DNMT3L shows high similarity to the de novo DNA
      methyltransferases, DNMT3A and DNMT3B, however, the amino acid residues needed
      for DNA cytosine methyltransferase activity have been lost from the DNMT3L
      protein sequence. Apart from methyltransferase activity, Dnmt3a and Dnmt3b serve
      as transcriptional repressors associating with histone deacetylase (HDAC)
      activity. Here we show that DNMT3L can also repress transcription by binding
      directly to HDAC1 protein. We have identified the PHD-like zinc finger of the
      ATRX domain as a main repression motif of DNMT3L, through which DNMT3L recruits
      the HDAC activity needed for transcriptional silencing. Furthermore, we show that
      DNMT3L protein contains an active nuclear localisation signal at amino acids 156
      159. These results describe DNMT3L as a co-repressor protein and suggest that a
      transcriptionally repressed chromatin organisation through HDAC activity is
      needed for establishment of genomic imprints.

PMID- 12177303
TI  - A functional gene discovery in the Fas-mediated pathway to apoptosis by analysis
      of transiently expressed randomized hybrid-ribozyme libraries.
AB  - The sequence of much of the human genome is now available and the next goal is to
      identify functional genes and to clarify their roles. We have recently developed
      a novel system for isolation of genes in the Fas- and TNF-alpha-mediated pathways
      to apoptosis using poly(A)-connected hammerhead ribozyme libraries with
      randomized substrate-binding arms at both the 5' and 3' ends of ribozymes. The
      transcripts of these hybrid ribozymes have a poly(A) motif that can recruit RNA
      helicases and, thus, they can effectively attack target sites. In the previous
      studies, hybrid ribozymes were stably expressed. In order to save selection
      times, in this study we adopted transiently expressed hybrid ribozymes. In the
      case of Fas-mediated apoptosis, when we transiently introduced these hybrid
      ribozyme libraries into Fas-expressing HeLa cells, we were able to isolate
      surviving clones that were resistant to or exhibited a delay in Fas-mediated
      apoptosis. We identified many pro-apoptotic genes and novel genes using this
      strategy with these transiently expressed hybrid-ribozyme libraries. In contrast,
      we identified significantly smaller numbers of candidate genes using conventional
      ribozyme libraries that were expressed transiently. Thus, when changes of a
      particular phenotype occur within a short period of time, our gene discovery
      system based on transiently expressed hybrid-ribozyme libraries should also be
      useful for the rapid identification of functional genes in the post-genome era.

PMID- 12177304
TI  - Effect of a neutralized phosphate backbone on the minor groove of B-DNA:
      molecular dynamics simulation studies.
AB  - Alternative models have been presented to provide explanations for the sequence
      dependent variation of the DNA minor groove width. In a structural model groove
      narrowing in A-tracts results from direct, short-range interactions among DNA
      bases. In an electrostatic model, the narrow minor groove of A-tracts is proposed
      to respond to sequence-dependent localization of water and cations. Molecular
      dynamics simulations on partially methylphosphonate substituted helical chains of
      d(TATAGGCCTATA) and d(CGCGAATTCGCG) duplexes have been carried out to help
      evaluate the effects of neutralizing DNA phosphate groups on the minor groove
      width. The results show that the time-average minor groove width of the GGCC
      duplex becomes significantly more narrow on neutralizing the phosphate backbone
      with methylphosphonates. The minor groove of the AATT sequence is normally narrow
      and the methylphosphonate substitutions have a smaller but measurable affect on
      this sequence. These results and models provide a system that can be tested by
      experiment and they support the hypothesis that the electrostatic environment
      around the minor groove affects the groove width in a sequence-dependent dynamic
      and time-average manner.

PMID- 12177305
TI  - The human XPC DNA repair gene: arrangement, splice site information content and
      influence of a single nucleotide polymorphism in a splice acceptor site on
      alternative splicing and function.
AB  - XPC DNA repair gene mutations result in the cancer-prone disorder xeroderma
      pigmentosum. The XPC gene spans 33 kb and has 16 exons (82-882 bp) and 15 introns
      (0.08-5.4 kb). A 1.6 kb intron was found within exon 5. Sensitive real- time
      quantitative reverse transcription-polymerase chain reaction methods were
      developed to measure full-length XPC mRNA (the predominant form) and isoforms
      that skipped exons 4, 7 or 12. Exon 7 was skipped in approximately 0.07% of XPC
      mRNAs, consistent with the high information content of the exon 7 splice acceptor
      and donor sites (12.3 and 10.4 bits). In contrast, exon 4 was skipped in
      approximately 0.7% of the XPC mRNAs, consistent with the low information content
      of the exon 4 splice acceptor (-0.1 bits). A new common C/A single nucleotide
      polymorphism in the XPC intron 11 splice acceptor site (58% C in 97 normals)
      decreased its information content from 7.5 to 5.1 bits. Fibroblasts homozygous
      for A/A had significantly higher levels (approximately 2.6-fold) of the XPC mRNA
      isoform that skipped exon 12 than those homozygous for C/C. This abnormally
      spliced XPC mRNA isoform has diminished DNA repair function and may contribute to
      cancer susceptibility.

PMID- 12177306
TI  - Subcellular trafficking of antisense oligonucleotides and down-regulation of bcl
      2 gene expression in human melanoma cells using a fusogenic liposome delivery
      system.
AB  - Antisense oligonucleotides (ODN) targeted to specific genes have shown
      considerable potential as therapeutic agents. The polyanionic charges carried by
      these molecules, however, present a barrier to efficient cellular uptake and
      consequently their biological effects on gene regulation are compromised. To
      overcome this obstacle, a rationally designed carrier system is desirable for
      antisense delivery. This carrier should assist antisense ODN penetrate the cell
      membrane and, once inside the cell, then release the ODN and make them available
      for target binding. We have developed a carrier formulation employing
      programmable fusogenic vesicles (PFV) as the antisense delivery mediator. This
      study investigates the intracellular fate of PFV-ODN and bioavailability of
      antisense ODN to cells. The subcellular distribution of PFV and ODN was examined
      by monitoring the trafficking of FITC-labeled ODN and
      rhodamine/phosphatidylethanolamine (Rh-PE)-labeled PFV using confocal microscopy.
      Fluorescently tagged ODN were first co-localized with the liposomal carrier in
      the cytoplasm, presumably in endosome/lysosome compartments, shortly after
      incubation of PFV-ODN with HEK 293 and 518A2 cells. Between 24 and 48 h
      incubation, however, separation of FITC-ODN from the carrier and subsequent
      accumulation in the nucleus was observed. In contrast, the Rh-PE label was
      localized to the cell cytoplasm. The enhanced cellular uptake achieved using the
      PFV carrier, compared to incubation of free ODN with cells, and subsequent
      release of ODN from the carrier resulted in significant down-regulation of mRNA
      expression. Specifically, G3139, an antisense construct targeting the apoptotic
      antagonist gene bcl-2, was examined in the human melanoma cell line 518A2. Upon
      exposure to PFV-encapsulated G3139, cells displayed a time-dependent reduction in
      bcl-2 message levels. The bcl-2 mRNA level was reduced by 50% after 24 h
      treatment and by approximately 80% after 72 h when compared to cells treated with
      free G3139, empty PFV or PFV-G3622, a control ODN sequence. Our results establish
      that ODN can be released from PFV after intracellular uptake and can then migrate
      to the nucleus and selectively down-regulate target mRNA.

PMID- 12177307
TI  - Manufacturing DNA microarrays from unpurified PCR products.
AB  - For the production of DNA microarrays from PCR products, purification of the the
      DNA fragments prior to spotting is a major expense in cost and time. Also, a
      considerable amount of material is lost during this process and contamination
      might occur. Here, a protocol is presented that permits the manufacture of
      microarrays from unpurified PCR products on aminated surfaces such as glass
      slides coated with the widely used poly(L-lysine) or aminosilane. The presence of
      primer molecules in the PCR sample does not increase the non-specific signal upon
      hybridisation. Overall, signal intensity on arrays made of unpurified PCR
      products is 94% of the intensity obtained with the respective purified molecules.
      This slight loss in signal, however, is offset by a reduced variation in the
      amount of DNA present at the individual spot positions across an array, apart
      from the considerable savings in time and cost. In addition, a larger number of
      arrays can be made from one batch of amplification products.

PMID- 12177308
TI  - A functional screening assay for the isolation of transcription factors.
AB  - Transcription factors (TFs) have been difficult to identify by bioinformatics,
      due to the heterogenous nature of the domains they are composed of. Therefore, we
      have developed a simple and generally applicable screening system for the
      identification of transcriptional activators, based on the presence of a
      functional transactivation domain (TAD). The system utilizes a retroviral vector
      to express a cDNA library as fusion genes with the yeast gal4 DNA-binding domain.
      This retroviral library is transduced into a murine NIH3T3-based reporter cell
      line carrying a stable integrated gal4 promoter-green fluorescent protein
      reporter gene. cDNA inserts encoding a functional TAD reconstitute a chimeric TF
      that activates the reporter gene. After fluorescence activated cell sorting
      (FACS) and expansion of GFP-positive cells, the responsible cDNA inserts are
      retrieved. From a cDNA library of cytokine-stimulated human umbilical vein
      endothelial cells (HUVEC), a number of known as well as potentially novel TFs
      were isolated, demonstrating the suitability of the system. The identification of
      other factors that are currently not associated with transcriptional regulation
      suggest additional functions for these proteins. Moreover, our results have
      focused attention on signaling pathways that have not been recognized previously
      in the context of endothelial cell biology.

PMID- 12177309
TI  - Analysis of RNA flexibility by scanning force spectroscopy.
AB  - Scanning force spectroscopy was used to measure the mechanical properties of
      double stranded RNA molecules in comparison with DNA. We find that, similar to
      the B-S transition in DNA, RNA molecules are stretched from the assumed A'
      conformation to a stretched conformation by applying a defined force (plateau
      force). The force depends on the G + C content of the RNA and is distinct from
      that required for the B-S transition of a homologous DNA molecule. After the
      conformational change, DNA can be further extended by a factor of 0.7 +/- 0.2 (S
      factor) before melting occurs and the binding of the molecule to the cantilever
      is finally disrupted. For RNA, the S-factor was higher (1.0 +/- 0.2) and more
      variable. Experiments to measure secondary structures in single stranded RNA
      yielded a large number of different force-distance curves, suggesting disruption
      and stretching of various secondary structures. Oriented attachment of the
      molecules to the substrate, a defined pick-up point and an increased resolution
      of the instrument could provide the means to analyse RNA secondary structures by
      scanning force spectroscopy.

PMID- 12177310
TI  - Determination of affinity, stoichiometry and sequence selectivity of minor groove
      binder complexes with double-stranded oligodeoxynucleotides by electrospray
      ionization mass spectrometry.
AB  - Electrospray mass spectrometry was evaluated regarding the reliability of the
      determination of the stoichiometries and equilibrium association constants from
      single spectra. Complexes between minor groove binders (Hoechst 33258, Hoechst
      33342, DAPI, netropsin and berenil) and 12mer oligonucleotide duplexes with a
      central sequence (A/T)4 flanked by G/C base pairs were chosen as model systems.
      To validate the electrospray ionization mass spectrometry (ESI-MS) method,
      comparisons were made with circular dichroism and fluorescence spectroscopy
      measurements. ESI-MS allowed the detection of minor (2 drug + DNA) species for
      Hoechst 33258, Hoechst 33342, DAPI and berenil with duplex d(GGGG(A/T)4GGGG).
      d(CCCC(A/T)4CCCC), which were undetectable with the other techniques. Assuming
      that the duplexes and the complexes have the same electrospray response factors,
      the equilbrium association constants of the 1:1 and 2:1 complexes were determined
      by ESI-MS, and the values show a good quantitative agreement with fluorescence
      determined constants for Hoechst 33258 and Hoechst 33342. It is also shown that
      ESI-MS can quickly give reliable information on the A/T sequence selectivity of a
      drug: the signal of a complex is directly related to the affinity of the drug for
      that particular duplex. The potential of ESI-MS as a qualitative and quantitative
      affinity screening method is emphasized.

PMID- 12177311
TI  - Counting CAG repeats in the Huntington's disease gene by restriction endonuclease
      EcoP15I cleavage.
AB  - Huntington's disease (HD) is a progressive neurodegenerative disorder with
      autosomal-dominant inheritance. The disease is caused by a CAG trinucleotide
      repeat expansion located in the first exon of the HD gene. The CAG repeat is
      highly polymorphic and varies from 6 to 37 repeats on chromosomes of unaffected
      individuals and from more than 30 to 180 repeats on chromosomes of HD patients.
      In this study, we show that the number of CAG repeats in the HD gene can be
      determined by restriction of the DNA with the endonuclease EcoP15I and subsequent
      analysis of the restriction fragment pattern by electrophoresis through non
      denaturing polyacrylamide gels using the ALFexpress DNA Analysis System. CAG
      repeat numbers in the normal (30 and 35 repeats) as well as in the pathological
      range (81 repeats) could be accurately counted using this assay. Our results
      suggest that this high-resolution method can be used for the exact length
      determination of CAG repeats in HD genes as well as in genes affected in related
      CAG repeat disorders.

PMID- 12177312
TI  - Novel ceftazidime-resistance beta-lactamases generated by a codon-based
      mutagenesis method and selection.
AB  - Four known and nine new ceftazidime-resistance beta-lactamases were generated by
      a novel, contaminating codon-based mutagenesis approach. In this method, wild
      type codons are spiked with a set of mutant codons during oligonucleotide
      synthesis, generating random combinatorial libraries of primers that contain few
      codon replacements per variant. Mutant codons are assembled by tandem addition of
      a diluted mixture of five Fmoc-dimer amidites to the growing oligo and a mixture
      of four DMTr-monomer amidites to generate 20 trinucleotides that encode a set of
      18 amino acids. Wild-type codons are assembled with conventional chemistry and
      the whole process takes place in only one synthesis column, making its automation
      feasible. The random and binomial behavior of this approach was tested in the
      polylinker region of plasmid pUC19 by the synthesis of three oligonucleotide
      libraries mutagenized at different rates and cloned as mutagenic cassettes.
      Additionally, the method was biologically assessed by mutating six contiguous
      codons that encode amino acids 237-243 (ABL numbering) of the TEM(pUC19) beta
      lactamase, which is functionally equivalent to the clinically important TEM-1
      beta-lactamase. The best ceftazidime-recognizing variant was a triple mutant,
      R164H:E240K: R241A, displaying a 333-fold higher resistance than the wild-type
      enzyme.

PMID- 12177313
TI  - Solid phase capturable dideoxynucleotides for multiplex genotyping using mass
      spectrometry.
AB  - We report an approach using solid phase capturable biotinylated
      dideoxynucleotides (biotin-ddNTPs) in single base extension for multiplex
      genotyping by mass spectrometry (MS). In this method, oligonucleotide primers
      that have different molecular weights and that are specific to the polymorphic
      sites in the DNA template are extended with biotin-ddNTPs by DNA polymerase to
      generate 3'-biotinylated DNA products. These products are then captured by
      streptavidin-coated solid phase magnetic beads, while the unextended primers and
      other components in the reaction are washed away. The pure extension DNA products
      are subsequently released from the solid phase and analyzed by matrix-assisted
      laser desorption/ionization time-of-flight MS. The mass of the extension products
      is determined using a stable oligonucleotide as a common internal mass standard.
      Since only the pure extension DNA products are introduced to the MS for analysis,
      the resulting mass spectrum is free of non-extended primer peaks and their
      associated dimers, which increases the accuracy and scope of multiplexing in
      single nucleotide polymorphism (SNP) analysis. The solid phase purification
      approach also facilitates desalting of the captured oligonucleotides, which is
      essential for accurate mass measurement by MS. We selected four biotin-ddNTPs
      with distinct molecular weights to generate extension products that have a 2-fold
      increase in mass difference compared to that with conventional ddNTPs. This
      increase in mass difference provides improved resolution and accuracy in
      detecting heterozygotes in the mass spectrum. Using this method, we
      simultaneously distinguished six nucleotide variations on synthetic DNA templates
      mimicking mutations in the p53 gene and two disease-associated SNPs in the human
      hereditary hemochromatosis gene.

PMID- 12177314
TI  - Use of hybridization kinetics for differentiating specific from non-specific
      binding to oligonucleotide microarrays.
AB  - Hybridization kinetics were found to be significantly different for specific and
      non-specific binding of labeled cRNA to surface-bound oligonucleotides on
      microarrays. We show direct evidence that in a complex sample specific binding
      takes longer to reach hybridization equilibrium than the non- specific binding.
      We find that this property can be used to estimate and to correct for the
      hybridization contributed by non-specific binding. Useful applications are
      illustrated including the selection of superior oligonucleotides, and the
      reduction of false positives in exon identification.

PMID- 12177315
TI  - DNA probes on beads arrayed in a capillary, 'Bead-array', exhibited high
      hybridization performance.
AB  - A DNA analysis platform called 'Bead-array' is presented and its features when
      used in hybridization detection are shown. In 'Bead-array', beads of 100- micro m
      diameter are lined in a determined order in a capillary. Each bead is conjugated
      with DNA probes, and can be identified by its order in the capillary. This probe
      array is easily produced by just arraying beads conjugated with probes into the
      capillary in a fixed order. The hybridization is also easily completed by
      introducing samples (1-300 micro l) into the capillary with reciprocal flow. For
      hybridization detection, as little as 1 amol of fluorescent-labeled oligo DNA was
      detected. The hybridization reaction was completed in 1 min irrespective of the
      amount of target DNA. When the number of target molecules was smaller than that
      of probe molecules on the bead, 10 fmol, almost all targets were captured on the
      bead. 'Bead-array' enables reliable and reproducible measurement of the target
      quantity. This rapid and sensitive platform seems very promising for various
      genetic testing tasks.

PMID- 12177317
TI  - X-ray absorption spectroscopy of bacterial sulfur globules.

PMID- 12177316
TI  - Removal of impurities from transcription factor preparations that alter their DNA
      binding properties.
AB  - Biochemical studies of transcriptional activators are important for understanding
      their detailed mechanism of action. Such experiments generally employ chimeric
      constructs comprised of fused DNA- binding and activation domains that are
      expressed in, and purified from, Escherichia coli, since full-length activators
      are usually difficult to express. We report here that such preparations contain
      chaperone impurities that affect the DNA-binding properties of the activator, for
      example sharply reducing the half-life of the protein-DNA complex. A simple
      method to remove these troublesome contaminants is described.

PMID- 12177319
TI  - Morphogenetic checkpoint in fission yeast? Yes!

PMID- 12177320
TI  - Morphogenetic checkpoint in fission yeast? No!

PMID- 12177321
TI  - A whole genome view of prokaryotic haem biosynthesis.

PMID- 12177322
TI  - Prospecting for novel lipase genes using PCR.
AB  - A PCR method suitable for the isolation of lipase genes directly from
      environmental DNA is described. The problems associated with the low levels of
      similarity between lipase genes were overcome by extensive analysis of conserved
      regions and careful primer design. Using this method, a lipase gene (oli-lipase)
      was isolated directly from environmental DNA. This lipase showed less than 20%
      similarity with other known lipases at the amino acid level. The study also
      revealed that distantly related members of the alpha/beta hydrolase superfamily
      share similar conserved motifs with the lipases, thus making these genes targets
      for gene prospecting by PCR.

PMID- 12177323
TI  - Evidence for protection of nitrogenase from O(2) by colony structure in the
      aerobic diazotroph Gluconacetobacter diazotrophicus.
AB  - Gluconacetobacter diazotrophicus is an endophytic diazotroph of sugarcane which
      exhibits nitrogenase activity when growing in colonies on solid media.
      Nitrogenase activity of G. diazotrophicus colonies can adapt to changes in
      atmospheric partial pressure of oxygen (pO(2)). This paper investigates whether
      colony structure and the position of G. diazotrophicus cells in the colonies are
      components of the bacterium's ability to maintain nitrogenase activity at a
      variety of atmospheric pO(2) values. Colonies of G. diazotrophicus were grown on
      solid medium at atmospheric pO(2) of 2 and 20 kPa. Imaging of live, intact
      colonies by confocal laser scanning microscopy and of fixed, sectioned colonies
      by light microscopy revealed that at 2 kPa O(2) the uppermost bacteria in the
      colony were very near the upper surface of the colony, while the uppermost
      bacteria of colonies cultured at 20 kPa O(2) were positioned deeper in the
      mucilaginous matrix of the colony. Disruption of colony structure by physical
      manipulation or due to 'slumping' associated with colony development resulted in
      significant declines in nitrogenase activity. These results support the
      hypothesis that G. diazotrophicus utilizes the path-length of colony mucilage
      between the atmosphere and the bacteria to achieve a flux of O(2) that maintains
      aerobic respiration while not inhibiting nitrogenase activity.

PMID- 12177324
TI  - Functional analysis of microbial communities in aerobic-anaerobic sequencing
      batch reactors fed with different phosphorus/carbon (P/C) ratios.
AB  - Fluorescence in situ hybridization (FISH) was used to analyse the community
      composition of a sequencing batch reactor (SBR) operating with aerobic-anaerobic
      cycling and fed acetate as its sole carbon source. Phosphorus was removed from
      the SBR microbiologically. Marked shifts in the community structure occurred as
      the phosphorus/carbon (P/C) ratio in the feed was changed. When the P/C ratio was
      shifted from 1:10 to 1:50, FISH analysis showed that the percentage of beta
      Proteobacteria fell from ca 77% of the total bacteria to ca 38%. This decrease in
      the beta-Proteobacteria coincided with a reduction in both the proportions of the
      beta-proteobacterial Rhodocyclus-related phosphorus-accumulating bacteria and the
      biomass phosphorus content. FISH/microautoradiography and FISH/poly beta
      hydroxyalkanoate (PHA) staining showed that the Rhodocyclus-related bacteria
      assimilated acetate and synthesized PHAs anaerobically, and that they accumulated
      phosphorus aerobically. No Acinetobacter spp. could be detected in any of the
      communities, casting further doubt on their role in phosphorus-removing activated
      sludge systems. As the feed P/C ratio decreased there was a corresponding
      increase in the proportion of alpha-Proteobacteria and, to a smaller extent, in
      the proportion of gamma-Proteobacteria; both the alpha- and gamma-Proteobacteria
      consisted mostly of tetrad-forming cocci, fitting the description of the so
      called 'G-bacteria' morphotype. The change in the proportions of Proteobacteria
      present paralleled increases in the biomass glycogen content. Both the alpha- and
      beta-proteobacterial 'G-bacterial' populations assimilated acetate and
      synthesized PHA anaerobically. The alpha-Proteobacteria are considered
      responsible for glycogen production in these SBR systems.

PMID- 12177325
TI  - Filamentous Chloroflexi (green non-sulfur bacteria) are abundant in wastewater
      treatment processes with biological nutrient removal.
AB  - Most filamentous bacteria in biological nutrient removal (BNR) processes have not
      been identified beyond their morphotype and simple staining reactions.
      Furthermore, the majority of sludge filaments observed under the microscope do
      not hybridize to commonly used phylogenetic probes for well characterized
      bacterial phyla such as the Proteobacteria, Actinobacteria, Firmicutes and
      BACTEROIDETES: Specific 16S rRNA-targeted oligonucleotide probes were designed
      for the phylum Chloroflexi (green non-sulfur bacteria) and optimized for use in
      fluorescence in situ hybridization. Chloroflexi have been implicated in BNR
      systems by phylogenetic identification of filamentous bacteria isolated by
      micromanipulation from sludge and culture-independent molecular phylogenetic
      surveys. The predominant morphotype responding to the probes was filamentous and
      these filaments were generally abundant in 10 Australian full-scale and two
      laboratory-scale BNR samples examined. Filamentous bacteria responding to a
      subdivision 1 Chloroflexi probe were rare in the samples, whereas subdivision 3
      Chloroflexi filaments were very common in some sludges. This is in direct
      contrast to results obtained from molecular phylogenetic surveys of BNR systems
      where most sludge 16S rDNA clones belong to subdivision 1 and only a few to
      subdivision 3. It is suggested that filamentous bacteria belonging to the
      Chloroflexi phylum account for a large fraction of phylogenetically
      uncharacterized filaments in BNR systems and are likely to be abundant in such
      systems on a global scale.

PMID- 12177326
TI  - nahR, encoding a LysR-type transcriptional regulator, is highly conserved among
      naphthalene-degrading bacteria isolated from a coal tar waste-contaminated site
      and in extracted community DNA.
AB  - In Pseudomonas putida strain G7, a LysR-type positive transcriptional activator
      protein encoded by nahR is necessary for activation of two operons involved in
      naphthalene catabolism [Schell, M. A. & Poser, E. F. (1989). J Bacteriol 171, 837
      846]. The role of an nahR homologue, NCIB-nahR, in another naphthalene
      metabolizing bacterium, P. putida NCIB 9816-4 was verified. Targeted disruption
      of NCIB-nahR by homologous recombination resulted in a growth defect in the
      presence of naphthalene or salicylate as sole carbon and energy source. The nahR
      homologues and intergenic regions between nahR-like and nahG-like genes from P.
      putida NCIB 9816-4 and seven bacteria native to a naphthalene-rich coal tar
      contaminated site were amplified by PCR using degenerate primers. The amplified
      nahR homologues and the intergenic regions were cloned and sequenced. Alignment
      of the deduced amino acid sequences from NahR homologues revealed that NahR-like
      proteins showed only minor variations in all investigated naphthalene-degrading
      isolates. The intergenic regions, together with known NahR-binding sites showed
      the consensus NahR-protein-binding sites (5'-ATTCACGCTN(2)TGAT-3'). Surprisingly,
      amplified intergenic regions from naphthalene-degrading micro-organisms native to
      this study site were 100% identical to that of the pDTG1 plasmid (an archetypal
      naphthalene-catabolic plasmid from Pseudomonas putida NCIB 9816-4), but the nahR
      coding regions were not. DNA representing the uncultured microbial community was
      extracted from six sediment samples with varying coal tar exposure histories. PCR
      amplification of nahR from sediment DNA was observed in contaminated samples, but
      in uncontaminated samples only following laboratory incubation with naphthalene.
      The sediment-derived PCR products were sequenced and also found to be almost
      identical to known nahR genes. Thus, the structure and function of nahR-nahG
      regulatory genes appear to be highly conserved.

PMID- 12177327
TI  - Identification of active methylotroph populations in an acidic forest soil by
      stable-isotope probing.
AB  - Stable-isotope probing (SIP) is a culture-independent technique that enables the
      isolation of DNA from micro-organisms that are actively involved in a specific
      metabolic process. In this study, SIP was used to characterize the active
      methylotroph populations in forest soil (pH 3.5) microcosms that were exposed to
      (13)CH(3)OH or (13)CH(4). Distinct (13)C-labelled DNA ((13)C-DNA) fractions were
      resolved from total community DNA by CsCl density-gradient centrifugation.
      Analysis of 16S rDNA sequences amplified from the (13)C-DNA revealed that
      bacteria related to the genera Methylocella, Methylocapsa, Methylocystis and
      Rhodoblastus had assimilated the (13)C-labelled substrates, which suggested that
      moderately acidophilic methylotroph populations were active in the microcosms.
      Enrichments targeted towards the active proteobacterial CH(3)OH utilizers were
      successful, although none of these bacteria were isolated into pure culture. A
      parallel analysis of genes encoding the key enzymes methanol dehydrogenase and
      particulate methane monooxygenase reflected the 16S rDNA analysis, but
      unexpectedly revealed sequences related to the ammonia monooxygenase of ammonia
      oxidizing bacteria (AOB) from the beta-subclass of the PROTEOBACTERIA: Analysis
      of AOB-selective 16S rDNA amplification products identified Nitrosomonas and
      Nitrosospira sequences in the (13)C-DNA fractions, suggesting certain AOB
      assimilated a significant proportion of (13)CO(2), possibly through a close
      physical and/or nutritional association with the active methylotrophs. Other
      sequences retrieved from the (13)C-DNA were related to the 16S rDNA sequences of
      members of the Acidobacterium division, the beta-Proteobacteria and the order
      Cytophagales, which implicated these bacteria in the assimilation of reduced one
      carbon compounds or in the assimilation of the by-products of methylotrophic
      carbon metabolism. Results from the (13)CH(3)OH and (13)CH(4) SIP experiments
      thus provide a rational basis for further investigations into the ecology of
      methylotroph populations in situ.

PMID- 12177328
TI  - Cloning, sequencing and expression of an alpha-amylase gene, amyA, from the
      thermophilic halophile Halothermothrix orenii and purification and biochemical
      characterization of the recombinant enzyme.
AB  - A recombinant clone expressing an amylase was identified from an Escherichia coli
      generated genomic library of the thermophilic, moderately halophilic, anaerobic
      bacterium Halothermothrix orenii by activity screening, and the gene encoding the
      enzyme was designated AmyA. The amyA gene was 1545 bp long, and encoded a 515
      residue protein composed of a 25 amino acid putative signal peptide and a 490
      amino acid mature protein. It possessed the five consensus regions characteristic
      of the alpha-amylase family and showed the greatest homology to the Bacillus
      megaterium group of alpha-amylases. The amyA gene was expressed in E. coli as a
      hexahistidine-tagged enzyme and purified. The purified recombinant enzyme was
      optimally active at 65 degrees C in 5% (w/v) NaCl at pH 7.5, with significant
      activity retained in the presence of up to 25% (w/v) NaCl. It had a specific
      activity of 22.32 U mg(-1) and required NaCl and CaCl(2) for optimum activity and
      thermostability. The relatively high proportion of acidic amino acids typically
      observed for many enzymes from halophiles was absent in H. orenii AmyA.

PMID- 12177329
TI  - Cross-talk between the L-sorbose and D-sorbitol (D-glucitol) metabolic pathways
      in Lactobacillus casei.
AB  - A gene encoding sorbitol-6-phosphate dehydrogenase (SorF) belonging to the
      sorbose operon (sorFABCDG) has been characterized in Lactobacillus casei.
      Inactivation of this gene revealed the presence of another sorbitol-6-phosphate
      dehydrogenase that was induced by D-sorbitol (D-glucitol). The gene encoding this
      activity (gutF) has also been isolated, sequenced and disrupted. The sorbitol-6
      phosphate dehydrogenase genes (sorF, gutF) were required for growth on L-sorbose
      and D-sorbitol, respectively. Biochemical and transcriptional analyses of the
      wild-type and mutant strains demonstrated that L-sorbose and D-sorbitol induced
      sorF and the gene encoding the sorbose operon activator (sorR), while the
      expression of gutF was only activated by D-sorbitol. Furthermore, these studies
      indirectly suggested that a common metabolite of the L-sorbose and D-sorbitol
      metabolic pathways (probably D-sorbitol 6-phosphate) would act as the effector of
      SorR. The same effector would also be the inducer of gutF, although the two
      pathways seem to be subject to distinct regulatory mechanisms.

PMID- 12177330
TI  - High-level resistance to class IIa bacteriocins is associated with one general
      mechanism in Listeria monocytogenes.
AB  - Class IIa bacteriocins may be used as natural food preservatives, yet resistance
      development in the target organisms is still poorly understood. In this study,
      the understanding of class IIa resistance development in Listeria monocytogenes
      is extended, linking the seemingly diverging results previously reported. Eight
      resistant mutants having a high resistance level (at least a 10(3)-fold increase
      in MIC), originating from five wild-type listerial strains, were independently
      isolated following exposure to four different class IIa bacteriocin-producing
      lactic acid bacteria (including pediocin PA-1 and leucocin A producers). Two of
      the mutants were isolated from food model systems (a saveloy-type sausage at 10
      degrees C, and salmon juice at 5 degrees C). Northern blot analysis showed that
      the eight mutants all had increased expression of EII(Bgl) and a phospho-beta
      glucosidase homologue, both originating from putative beta-glucoside-specific
      phosphoenolpyruvate-dependent phosphotransferase systems (PTSs). However,
      disruption of these genes in a resistant mutant did not confer pediocin
      sensitivity. Comparative two-dimensional gel analysis of proteins isolated from
      mutant and wild-type strains showed that one spot was consistently missing in the
      gels from mutant strains. This spot corresponded to the MptA subunit of the
      mannose-specific PTS, found only in the gels of wild-type strains. The mptACD
      operon was recently shown to be regulated by the sigma(54) transcription factor
      in conjunction with the activator ManR. Class IIa bacteriocin-resistant mutants
      having defined mutations in mpt or manR also exhibited the two diverging PTS
      expression changes. It is suggested here that high-level class IIa resistance in
      L. monocytogenes and at least some other Gram-positive bacteria is developed by
      one prevalent mechanism, irrespective of wild-type strain, class IIa bacteriocin,
      or the tested environmental conditions. The changes in expression of the beta
      glucoside-specific and the mannose-specific PTS are both influenced by this
      mechanism. The current understanding of the actual cause of class IIa resistance
      is discussed.

PMID- 12177331
TI  - Characterization of a new efflux pump, MexGHI-OpmD, from Pseudomonas aeruginosa
      that confers resistance to vanadium.
AB  - Vanadium has an antibacterial activity against Pseudomonas aeruginosa, especially
      under conditions of iron limitation. Some degree of resistance to V is inducible
      by prior exposure to the metal. One mutant (VS1) with a higher sensitivity to V
      was obtained by transposon mutagenesis of P. aeruginosa PA 59.20, a clinical
      isolate. This mutant had an insertion in a non-coding region, upstream of a
      cluster of four genes. Three of them show similarities to genes corresponding to
      known P. aeruginosa antibiotic efflux systems, including an efflux protein, a
      membrane fusion protein and an outer-membrane porin. This cluster was named
      mexGHI-opmD. By allelic exchange, three mutants, ncr (for non-coding region),
      mexI and opmD were constructed in P. aeruginosa PAO1. Next to V sensitivity, the
      ncr, mexI and opmD mutants also showed reduced production of elastase,
      rhamnolipids, pyocyanine, pyoverdine and had reduced swarming motility,
      phenotypes that are known to be regulated by quorum sensing. All wild-type
      phenotypes, including growth in the presence of V, were restored by
      complementation with the complete cluster. The production of N-acyl-homoserine
      lactones (AHLs) was detected using the Chromobacter violaceum bioassay. Total
      extracts from the three mutants failed to induce the production of violacein by
      C. violaceum, although AHLs were detected by TLC and C. violaceum overlay.
      Violacein production was restored by complementation with mexGHI-opmD. The opmD
      mutant grew very slowly in LB or CAA medium, indicating that OpmD has an
      important physiological function for the cell. In conclusion, it is believed that
      the MexGHI-OpmD pump is probably involved in AHL homeostasis in P. aeruginosa.

PMID- 12177332
TI  - Analysis of spore cortex lytic enzymes and related proteins in Bacillus subtilis
      endospore germination.
AB  - The location and function of recognized cortex-lytic enzymes of Bacillus subtilis
      have been explored, and the involvement in germination of a number of related
      proteins tested. The SleB and CwlJ proteins are cortex-lytic enzymes, partially
      redundant in function, that are required together for effective cortex hydrolysis
      during B. subtilis spore germination. Spores were fractionated, and Western
      blotting of individual fractions suggests that the CwlJ protein is localized
      exclusively to the outer layers, or integument. The second spore-lytic enzyme,
      SleB, is localized both in the inner membrane of the spore and in the integument
      fraction. Neither protein changes location or size as the spore germinates. The
      ypeB gene is the second gene in a bicistronic operon with sleB. The SleB protein
      is absent from ypeB mutant spores, suggesting that YpeB is required for its
      localization or stabilization. In fractions of wild-type spores, the YpeB protein
      is found in the same locations as SleB - in both the inner membrane and the
      integument. As the absence of CwlJ protein does not affect the overall RP-HPLC
      profile of peptidoglycan fragments in germinating spores, this enzyme's
      hydrolytic specificity could not be defined. The effects of inactivation of
      several homologues of cortex-lytic enzymes of as yet undefined function were
      examined, by testing null mutants for their germination behaviour by OD(600) fall
      and by RP-HPLC of peptidoglycan fragments from dormant and germinating spores.
      The YaaH enzyme is responsible for a likely epimerase modification of
      peptidoglycan during spore germination, but the loss of this activity does not
      appear to affect the spore's ability to complete germination. Unlike the other
      cortex-lytic enzymes, the YaaH protein is present in large amounts in the spore
      germination exudate of B. subtilis. Mutants lacking either YdhD or YvbX, both
      homologues of YaaH, had no detectable alteration in either dormant or germinating
      spore peptidoglycan, and germinated normally. The ykvT gene, which encodes a
      protein of the SleB/CwlJ family, has no apparent association with germination:
      the gene is expressed in vegetative cells, and mutants lacking YkvT have no
      detectable phenotype.

PMID- 12177333
TI  - Permeability of Coxiella burnetii to ribonucleosides.
AB  - Knowledge about transport in Coxiella burnetii, an obligate phagolysosomal
      parasite, is incomplete. The authors investigated the capability of isolated,
      intact, host-free Coxiella to transport ribonucleosides while incubated at a pH
      value typical of lysosomes. Because of the low activities and limitations of
      obtaining experimental quantities of isolated, purified Coxiella, incorporation
      of substrate into nucleic acid was used as a trap for determination of uptake
      abilities. Virulent wild-type (phase I) organisms possessed uptake capability for
      all ribonucleosides. Both phase I and phase II (avirulent) organisms incorporated
      the purine nucleosides guanosine, adenosine and inosine, and showed a more
      limited uptake of thymidine and uridine. Both phases were poorly active in
      cytidine uptake. Neither phase of the organism was capable of transport and
      incorporation of NTPs, CMP, cytosine or uracil. Water space experiments confirmed
      that the uptake process concentrated the purine nucleosides within the cytoplasm
      of both wild-type and phase II Coxiella via a low-pH-dependent mechanism.
      Comparison of uptake rates in Escherichia coli versus Coxiella verified that the
      incorporation of ribonucleosides by Coxiella is a slow process. It is concluded
      that Coxiella possesses some transport pathways consistent with utilization of
      pools of nucleosides found within its host cell lysosomal pathway.

PMID- 12177334
TI  - The signal transducer P(II) and bicarbonate acquisition in Prochlorococcus
      marinus PCC 9511, a marine cyanobacterium naturally deficient in nitrate and
      nitrite assimilation.
AB  - The amino acid sequence of the signal transducer P(II) (GlnB) of the oceanic
      photosynthetic prokaryote Prochlorococcus marinus strain PCC 9511 displays a
      typical cyanobacterial signature and is phylogenetically related to all known
      cyanobacterial glnB genes, but forms a distinct subclade with two other marine
      cyanobacteria. P(II) of P. marinus was not phosphorylated under the conditions
      tested, despite its highly conserved primary amino acid sequence, including the
      seryl residue at position 49, the site for the phosphorylation of the protein in
      the cyanobacterium Synechococcus PCC 7942. Moreover, P. marinus lacks nitrate and
      nitrite reductase activities and does not take up nitrate and nitrite. This
      strain, however, expresses a low- and a high-affinity transport system for
      inorganic carbon (C(i); K(m,app) 240 and 4 micro M, respectively), a result
      consistent with the unphosphorylated form of P(II) acting as a sensor for the
      control of C(i) acquisition, as proposed for the cyanobacterium Synechocystis PCC
      6803. The present data are discussed in relation to the genetic information
      provided by the P. marinus MED4 genome sequence.

PMID- 12177335
TI  - Regulation of phasin expression and polyhydroxyalkanoate (PHA) granule formation
      in Ralstonia eutropha H16.
AB  - Regulation of expression of the phasin PhaP, which is the major protein at the
      surface of polyhydroxyalkanoate (PHA) granules in Ralstonia eutropha H16, was
      studied and analysed at the molecular level. The regulation of PhaP expression is
      achieved by an autoregulated repressor, which is encoded by phaR in R. eutropha.
      The occurrence of PhaR homologues and the organization of phaR genes was analysed
      in detail in 29 different bacteria. Three kinds of molecule to which PhaR binds
      were identified in cells of R. eutropha, as revealed by gel-mobility-shift
      assays, DNaseI footprinting, cell fractionation, immunoelectron microscopy
      studies employing anti-PhaR antibodies raised against purified N-terminal
      hexahistidine-tagged PhaR and in vitro binding studies employing artificial PHA
      granules. PhaR binds upstream of phaP at two sites comprising the transcriptional
      start site plus the -10 region and a region immediately upstream of the -35
      region of the sigma(70) promoter of phaP, where two imperfect 12 bp repeat
      sequences (GCAMMAAWTMMD) were identified on the sense and anti-sense strands.
      PhaR also binds 86 bp upstream of the phaR translational start codon, where the
      sigma(54)-dependent promoter was identified. PhaR also binds to the surface of
      PHA granules. In the cytoplasm of a phaROmegaKm mutant of R. eutropha H16,
      increased quantities of PhaP were detected and the cells formed by this strain
      were much smaller and had many more PHA granules present than the wild-type.
      These data support the following model for the regulation of phaP expression.
      Under cultivation conditions not permissive for PHA biosynthesis or in mutants
      defective in PHA biosynthesis, PhaR binds to the phaP promoter region and
      represses transcription of this gene. After the onset of PHA biosynthesis, under
      conditions that are permissive for the formation of nascent granules, PhaR binds
      to PHA granules and phaP is transcribed. At the later stages of PHA accumulation,
      PhaR no longer binds to the granules and the transcription of phaP is again
      repressed. In addition to this, phaR expression is subject to autoregulation.
      Excess PhaR that has not bound to the phaP upstream region or to PHA granules
      binds to the phaR upstream region, thereby repressing its own transcription.

PMID- 12177336
TI  - A zinc metalloprotease inhibitor, Inh, from the insect pathogen Photorhabdus
      luminescens.
AB  - The entomopathogen Photorhabdus luminescens secretes many proteins during the
      late stages of insect larvae infection and during in vitro laboratory culture.
      The authors have previously characterized and purified a 55 kDa zinc
      metalloprotease, PrtA, from culture supernatants of P. luminescens. PrtA is
      secreted via a classical type I secretory pathway and is encoded within the
      operon prtA-inh-prtBCD. The 405 bp inh gene encodes a 14.8 kDa pre-protein that
      is translocated to the periplasm by the classical signal-peptide-dependent sec
      pathway, yielding the mature 11.9 kDa inhibitor Inh. Inh is a specific inhibitor
      of the protease PrtA. This study describes the purification of Inh and the
      initial characterization of its in vitro protease inhibition properties.

PMID- 12177337
TI  - The principal determinants for the structure of the substrate-binding pocket are
      located within a central core of a biphenyl dioxygenase alpha subunit.
AB  - Protein engineering by segment exchange was used to distinguish between regions
      of major and minor influence on the structure of the substrate-binding pocket of
      a biphenyl dioxygenase (BDO). Eight chimaeric enzyme systems were generated that
      each consisted of a hybrid hydroxylase alpha subunit (BphA1) containing segments
      from Burkholderia sp. strain LB400 and Rhodococcus globerulus P6, and of a
      hydroxylase beta subunit (BphA2), a ferredoxin (BphA3) and a ferredoxin reductase
      (BphA4) from strain LB400. All hybrid bphA1 genes were expressed at high levels.
      Seven of the resulting fusion subunits functionally interacted with the other
      polypeptides of the dioxygenase system to yield catalytically active enzymes.
      Changes in the regiospecificity of substrate attack, monitored by the formation
      of seventeen different dioxygenation products obtained from seven
      chlorobiphenyls, were used to monitor effects of segment exchanges on the
      structure of the BDO substrate-binding site. Exchanges of neither the beta
      subunit nor the N- and C-terminal regions of the alpha subunit exerted
      significant influences. All BDO regions that showed major effects on the
      substrate-binding pocket were located between approximately positions 165 and 395
      of the alpha subunit. Within this part of the enzyme, in addition to segments
      identified previously, a subregion which is involved in ligation of the
      mononuclear iron significantly influenced the regiospecificity of substrate
      dioxygenation. Moreover, the results indicate that the construction of
      appropriate hybrid genes may be used as a general strategy to overcome problems
      in obtaining heterologous BDO activities in Escherichia coli or other host
      organisms.

PMID- 12177338
TI  - The ferric uptake regulator of Pseudomonas aeruginosa has no essential cysteine
      residues and does not contain a structural zinc ion.
AB  - The ferric uptake regulator (Fur) of Pseudomonas aeruginosa was expressed in
      Escherichia coli in its native form and as a fusion to the maltose-binding
      protein (MBP). Fur from the MBP fusion bound to MBP after proteolytic cleavage,
      and the two could only be separated by partial unfolding. The refolded protein
      was in the same conformation as native protein (as judged by circular dichroism
      and fluorescence spectroscopies) and was fully active in DNA-binding assays. As
      prepared native Fur contained small amounts of Zn(2+) that were easily removed by
      treatment with EDTA, and apo-protein could be reconstituted with approximately
      one Zn(2+) ion per monomer. Thus, the P. aeruginosa Fur can probably accommodate
      a single Zn(2+) ion bound to the metal-sensing site. The single cysteine residue
      of P. aeruginosa Fur aligns with a cysteine in other members of the Fur family
      that is essential for activity of the E. coli protein, and is believed to provide
      one of the ligands to a structural Zn(2+) ion. This cysteine residue was shown to
      be dispensable for the in vivo activity of P. aeruginosa Fur, which is consistent
      with the suggestion that the P. aeruginosa protein does not contain a structural
      Zn(2+) ion. Members of the Fur family contain a highly conserved His-His-Asp-His
      motif. Alanine substitutions of residues in this motif showed His-87 and His-89
      of P. aeruginosa Fur to be essential for activity, whilst His-86 and Asp-88 are
      partially dispensable.

PMID- 12177339
TI  - Regulation of polyphenol oxidase activities and melanin synthesis in Marinomonas
      mediterranea: identification of ppoS, a gene encoding a sensor histidine kinase.
AB  - Marinomonas mediterranea is a melanogenic marine bacterium that expresses two
      different polyphenol oxidases. One of them is a multipotent laccase able to
      oxidize a wide range of substrates. The second enzyme is an SDS-activated
      tyrosinase. Using transposon mutagenesis, a mutant affected in the regulation of
      both polyphenol oxidase activities and melanogenesis has been isolated. The
      sequencing of the gene disrupted by the mini-Tn10 transposon in this mutant
      indicates that it encodes a hybrid sensor kinase. This sensor kinase shows three
      phosphorylated conserved domains: the transmitter domain containing a histidine
      site typical of sensor kinases, a receiver domain with an aspartate residue and
      an additional phosphotransferase domain with a second conserved histidine. This
      structural organization is characteristic of kinases participating in a
      phosphorelay system. Northern blot and lacZ operon fusions indicate that the
      multipotent laccase activity is regulated not only by PpoS but also by growth
      phase at the transcriptional level. These results suggest that PPO activities and
      melanin synthesis play a role in the adaptive response of M. mediterranea to
      stressful environmental conditions.

PMID- 12177340
TI  - Mechanisms of in vitro development of resistance to metronidazole in Trichomonas
      vaginalis.
AB  - Development of resistance against metronidazole and mechanisms responsible for
      this process were studied in a sexually transmitted pathogen of humans,
      Trichomonas vaginalis. Monitoring of changes in metabolism and protein expression
      that accompanied increasing resistance of strains derived from a common drug
      susceptible parent (TV 10-02) showed the multistep character of the process. The
      aerobic type of resistance known to occur in isolates from patients non
      responsive to treatment appeared at the earliest stage, followed by development
      of the anaerobic type of resistance which was accompanied by gradual loss of
      hydrogenosomal proteins associated with drug-activating pathways
      [pyruvate:ferredoxin oxidoreductase (PFOR), hydrogenase, ferredoxin].
      Unexpectedly, the loss of PFOR did not result in acquisition of full anaerobic
      resistance, thus indicating an alternative source of electrons required for the
      drug activation. These data suggest involvement of the oxidative decarboxylation
      of malate in hydrogenosomes, catalysed by NAD(+)-dependent malic enzyme and
      subsequent transfer of reduced equivalents to the drug via NADH:ferredoxin
      oxidoreductase and ferredoxin. Accordingly, all components of this pathway were
      eliminated before the resistance was fully developed. Resistant Trichomonas
      vaginalis compensated the impaired function of hydrogenosomes by enhanced
      conversion of pyruvate to lactate in the cytosol. Further analysis of the two key
      enzymes involved in metronidazole activation by Northern blotting and assay for
      nascent mRNA showed that the insufficient expression of the PFOR protein results
      from decreased gene transcription, while down-regulation of malic enzyme is
      controlled at the mRNA level.

PMID- 12177341
TI  - Plasmid-borne macrolide resistance in Micrococcus luteus.
AB  - A plasmid designated pMEC2 which confers resistance to erythromycin, other
      macrolides, and lincomycin was detected in Micrococcus luteus strain MAW843
      isolated from human skin. Curing of this approximately 4.2 kb plasmid from the
      host organism resulted in erythromycin sensitivity of the strain. Introduction of
      pMEC2 into a different M. luteus strain conferred erythromycin resistance upon
      this strain. Macrolide resistance in M. luteus MAW843 was an inducible trait.
      Induction occurred at subinhibitory erythromycin concentrations of about 0.02
      0.05 micro g ml(-1). Erythromycin and oleandomycin were inducers, while
      spiramycin and tylosin exerted no significant inducer properties. With
      heterologous expression experiments in Corynebacterium glutamicum, using hybrid
      plasmid constructs and deletion derivatives thereof, it was possible to narrow
      down the location of the plasmid-borne erythromycin-resistance determinant to a
      region of about 1.8 kb of pMEC2. Sequence analysis of the genetic determinant,
      designated erm(36), identified an ORF putatively encoding a 281-residue protein
      with similarity to 23S rRNA adenine N(6)-methyltransferases. erm(36) was most
      related (about 52-54% identity) to erythromycin-resistance proteins found in high
      G+C Gram-positive bacteria, including the (opportunistic) pathogenic
      corynebacteria Corynebacterium jeikeium, C. striatum, C. diphtheriae and
      Propionibacterium acnes. This is believed to be the first report of a plasmid
      borne, inducible antibiotic resistance in micrococci. The possible role of non
      pathogenic, saprophytic micrococci bearing antibiotic-resistance genes in the
      spreading of these determinants is discussed.

PMID- 12177342
TI  - Differential effects of Kid toxin on two modes of replication of lambdoid
      plasmids suggest that this toxin acts before, but not after, the assembly of the
      replication complex.
AB  - Kid is a small protein that is encoded by plasmid R1. It is a toxin that belongs
      to a killer system that ensures the stability of the plasmid in host cells. The
      results of previous studies have suggested that Kid is an inhibitor of DNA
      replication, possibly acting at the onset of initiation. Here, the authors tested
      the effects of Kid on orilambda-intitiated and oriJ-initiated replication, which
      may be driven by both the newly assembled replication complex and the heritable
      complex. It was found that Kid inhibits only replication that is driven by the
      newly assembled replication complex. The authors also report that Kid inhibits
      ColE1-like plasmid replication in vivo, in agreement with the previously reported
      inhibition of ColE1 during in vitro replication. It is proposed that the Kid
      toxin acts at the level of replication either by preventing de novo assembly of
      the replication complex or by impairing the functional interactions of the
      replication complex at the initiation stage.

PMID- 12177343
TI  - Diversity within inc genes of clinical Chlamydia trachomatis variant isolates
      that occupy non-fusogenic inclusions.
AB  - The obligately intracellular chlamydiae are bacterial pathogens that occupy
      intracellular vacuoles, termed inclusions, as they develop and multiply. Typical
      Chlamydia trachomatis isolates occupy inclusions that fuse with other C.
      trachomatis inclusions within cells infected with multiple elementary bodies
      (wild-type phenotype). The authors of this study have recently described C.
      trachomatis isolates that form multiply-lobed, non-fusogenic inclusions within
      single cells infected with multiple elementary bodies (variant phenotype).
      Inclusions formed by these isolates uniformly lacked the protein IncA on the
      inclusion membrane (IM). In the present work, the study of the C. trachomatis
      inclusion phenotype has been expanded to include 27 variant and 13 wild-type
      isolates. Twenty-four of the 27 variant isolates were IncA-negative, as detected
      by fluorescence microscopy and immunoblotting, but three variants localized IncA
      to the IM. The IncA-positive variants formed inclusions that fused, at a reduced
      rate, with those occupied by wild-type isolates and with inclusions formed by
      other IncA-positive variants. Nucleotide-sequence analysis of the incA sequences
      from the variant isolates identified a variety of distinct sequence polymorphisms
      relative to incA from wild-type strains. The authors also demonstrate that a
      second Inc protein, CT223p, is not found in the IM in selected C. trachomatis
      isolates. No change in the structure or the fusogenicity of the inclusions was
      associated with the presence or absence of CT223p.

PMID- 12177344
TI  - BfpU, a soluble protein essential for type IV pilus biogenesis in
      enteropathogenic Escherichia coli.
AB  - A cluster of 14 genes located on the large plasmid of enteropathogenic
      Escherichia coli (EPEC) strains is sufficient to direct the biogenesis of the
      type IV bundle-forming pilus (BFP) in a recombinant E. coli host. The fifth gene
      in the cluster, bfpU, encodes a protein that is predicted to be localized to the
      periplasmic space. To determine whether BfpU is necessary for pilus biogenesis,
      the authors constructed a non-polar bfpU mutant EPEC strain by allelic exchange.
      The mutant strain was unable to perform localized adherence and auto-aggregation,
      two phenotypes associated with BFP expression, and it failed to make BFP. These
      phenotypes were restored to the bfpU mutant by a plasmid containing bfpU. There
      was no difference between the wild-type and bfpU mutant strains in their
      expression or processing of the pre-pilin protein or in their localization of the
      pilin protein in the inner and outer membranes. Fractionation studies revealed
      that BfpU is completely soluble and is detected in both the periplasm and the
      cytoplasm. Thus, BfpU represents a novel protein required for type IV pilus
      assembly.

PMID- 12177345
TI  - Enteroinvasive Escherichia coli virulence-plasmid-carried apyrase (apy) and ospB
      genes are organized as a bicistronic operon and are subject to differential
      expression.
AB  - In Shigella flexneri and enteroinvasive Escherichia coli (EIEC) the expression of
      the virulence-plasmid(pINV)-carried potential pathogenesis-associated apy gene,
      which encodes apyrase (ATP diphosphohydrolase), is regulated by the same
      regulators that govern the expression of virulence genes. To understand the
      transcriptional organization of the apy gene, the authors sequenced an 8023 bp
      PstI fragment of the pINV of EIEC strain HN280, which encompasses apy as well as
      its adjacent genes. The PstI fragment displays 99% identity with the
      corresponding fragment of pWR100, the pINV of S. flexneri strain M90T, and
      contains four genes. One of these genes, ospB, encodes a secreted protein of
      unknown activity and is located immediately upstream of apy. Analyses of
      sequence, Northern hybridization, RT-PCR and primer extension data and
      transcriptional fusions indicated that ospB and apy are co-transcribed as a 2 kb
      bicistronic, temperature-regulated mRNA from an upstream promoter that precedes
      ospB. The 2 kb mRNA is post-transcriptionally processed in the intercistronic
      ospB-apy region, leading to the considerable accumulation of a more stable 1 kb
      apy-specific mRNA (half-life of 2.2+/-0.3 min, versus 27+/-4 s for the 2 kb
      transcript). Upon temperature induction, peak expression of the ospB-apy operon
      occurs when bacteria enter into the late phases of bacterial growth, where the
      apy-specific transcript was found to be much more prevalent if compared to the
      ospB-apy transcript.

PMID- 12177346
TI  - Evolution of multi-gene segments in the mutS-rpoS intergenic region of Salmonella
      enterica serovar Typhimurium LT2.
AB  - The nucleotide sequence of the 12.6 kb region between the mutS and rpoS genes of
      Salmonella enterica serovar Typhimurium LT2 (S. typhimurium) was compared to
      other enteric bacterial mutS-rpoS intergenic regions. The mutS-rpoS region is
      composed of three distinct segments, designated HK, O and S, as defined by
      sequence similarities to contiguous ORFs in other bacteria. Inverted chromosomal
      orientations of each of these segments are found between the mutS and rpoS genes
      in related ENTEROBACTERIACEAE: The HK segment is distantly related to a cluster
      of seven ORFs found in Haemophilus influenzae and a cluster of five ORFs found
      between the mutS and rpoS genes in Escherichia coli K-12. The O segment is
      related to the mutS-rpoS intergenic region found in E. coli O157:H7 and Shigella
      dysenteriae type 1. The third segment, S, is common to diverse Salmonella
      species, but is absent from E. coli. Despite the extensive collinearity and
      conservation of the overall genetic maps of S. typhimurium and E. coli K-12, the
      insertions, deletions and inversions in the mutS-rpoS region provide evidence
      that this region of the chromosome is an active site for horizontal gene transfer
      and rearrangement.

PMID- 12177347
TI  - Protein signatures distinctive of chlamydial species: horizontal transfers of
      cell wall biosynthesis genes glmU from archaea to chlamydiae and murA between
      chlamydiae and Streptomyces.
AB  - Chlamydiae are major human and animal pathogens. Based on alignments of different
      protein sequences, a number of conserved indels (insertion/deletions) were
      identified that appear to be unique and distinctive characteristics of the
      chlamydial species. The identified signatures include one 16 aa and two single aa
      inserts in the enzyme UDP-N-acetylglucosamine 1-carboxyvinyltransferase (MurA), a
      1 aa insert in protein synthesis elongation factor P (EF-P), a 1 aa insert in the
      Mg(2+) transport protein (MgtE), a 1 aa insert in the carboxy-terminal protease
      and a 1 aa deletion in the tRNA (guanine-N(1)-)-methyltransferase (TrmD) protein.
      The homologues of these proteins are found in all major groups of bacteria and
      the observed indels are present in all available chlamydial sequences but not in
      any other species (except for the large insert in MurA in Streptomyces). The
      validity of three of these signatures (MurA, EF-P and MgtE) was tested by PCR
      amplifying the signature regions from several chlamydial species for which no
      sequence information was available. All Chlamydiaceae species for which specific
      fragments could be amplified (Chlamydia suis, Chlamydophila abortus,
      Chlamydophila psittaci, Chlamydophila felis) contained the expected signatures.
      Additionally, a fragment of the murA gene from Waddlia chondrophila and the efp
      gene from Simkania negevensis, two chlamydia-like species, were also cloned and
      sequenced. The presence of respective indels in these species provides strong
      evidence that they are specifically related to the traditional chlamydial
      species, and that these signatures may be distinctive of the entire Chlamydiales
      order. A 17 aa conserved indel was also identified in the cell wall biosynthesis
      enzyme UDP-N-acetylglucosamine pyrophosphorylase (GlmU), which is shared by all
      archaeal and chlamydial homologues. The gene for this protein is indicated to
      have been horizontally transferred from an archaeon to a common ancestor of the
      chlamydiae. The results also support a lateral transfer of the murA gene between
      chlamydiae and STREPTOMYCES: The large inserts in these peptidoglycan synthesis
      related genes in chlamydiae could account for their unusual cell-wall
      characteristics. These signatures are also potentially useful for screening of
      the chlamydiae species.

PMID- 12177348
TI  - Small genome of Candidatus Blochmannia, the bacterial endosymbiont of Camponotus,
      implies irreversible specialization to an intracellular lifestyle.
AB  - Blochmannia (Candidatus Blochmannia gen. nov.) is the primary bacterial
      endosymbiont of the ant genus CAMPONOTUS: Like other obligate endosymbionts of
      insects, Blochmannia occurs exclusively within eukaryotic cells and has
      experienced long-term vertical transmission through host lineages. In this study,
      PFGE was used to estimate the genome size of Blochmannia as approximately 800 kb,
      which is significantly smaller than its free-living relatives in the
      enterobacteria. This small genome implies that Blochmannia has deleted most of
      the genetic machinery of related free-living bacteria. Due to restricted gene
      exchange in obligate endosymbionts, the substantial gene loss in Blochmannia and
      other insect mutualists may reflect irreversible specialization to a host
      cellular environment.

PMID- 12177349
TI  - Conflicting phylogeographic patterns in rRNA and nifD indicate regionally
      restricted gene transfer in Bradyrhizobium.
AB  - Major differences in evolutionary relationships of the 16S rRNA gene and the
      nitrogenase alpha-subunit gene (nifD) were observed among 38 strains of
      Bradyrhizobium sp. nodule bacteria from North America, Central America, Asia and
      Australia. Two lineages were evident in the 16S rRNA phylogeny representing
      strains related to Bradyrhizobium japonicum (29 isolates) or Bradyrhizobium
      elkanii (9 isolates). Both clades were distributed across most or all of the
      geographic regions sampled. By contrast, in the nifD tree almost all isolates
      were placed into one of three groups each exclusively composed of taxa from a
      single geographic region (North Temperate, Central America or Australia).
      Isolates that were closely related or identical in gene sequence at one locus
      often had divergent sequences at the other locus and a partition homogeneity test
      indicated that the 16S rRNA and nifD phylogenies were significantly incongruent.
      No evidence for any gene duplication of nifD was found by Southern hybridization
      analysis on a subset of the strains, so unrecognized paralogy is not likely to be
      responsible for the discrepancy between 16S rRNA and nifD tree topologies. These
      results are consistent with a model whereby geographic areas were initially
      colonized by several diverse 16S rRNA lineages, with subsequent horizontal gene
      transfer of nifD leading to increased nifD sequence homogeneity within each
      regional population.

PMID- 12177351
TI  - Silencing of the Escherichia coli bgl operon by RpoS requires Crl.
AB  - Silencing of the Escherichia coli bgl operon is mediated by histone-like protein
      H-NS and affected by other pleiotropic regulators, including sigma factor RpoS.
      Silencing is relieved and the bgl operon is activated in hns mutants and by
      mutations that map in the vicinity of the bgl promoter. However, the expression
      level of activated bgl operon derivatives varies with the strain background. Here
      it is shown that the repression of the bgl operon by RpoS requires Crl. Crl is a
      protein that is necessary for the RpoS-dependent expression of the csgBA operon
      and that enhances the expression of other RpoS-dependent genes. In a Crl-negative
      strain RpoS had no effect on the bgl operon. The crl gene maps close to the proBA
      locus in the lac operon region and is deleted in many commonly used E. coli
      strains. Crl may therefore account for some of the observed strain-dependent
      variations of bgl operon expression levels and effects of pleiotropic regulators
      on bgl operon regulation.

PMID- 12177350
TI  - Priming reverse transcription with oligo(dT) does not yield representative
      samples of Mycobacterium tuberculosis cDNA.
AB  - Several recent publications have suggested that oligo(dT) can prime reverse
      transcription of several mycobacterial mRNAs. To determine if this is the case
      for most Mycobacterium tuberculosis mRNA species, reverse transcription reactions
      of M. tuberculosis RNA were primed with oligo(dT) or with other primers that did
      not target polyadenylylated sequences, and the resultant cDNA product was
      evaluated. Priming with oligo(dT) yielded more cDNA than priming with an
      arbitrary primer for only 1 of 12 unrelated M. tuberculosis genes, as measured by
      competitive PCR. Priming with oligo(dT) yielded cDNA for only 30% of the genes
      primed for by 37 M. tuberculosis genome-directed oligonucleotides, as assessed by
      hybridization of cDNA with an M. tuberculosis microarray. These data demonstrate
      that priming of reverse transcription of mycobacterial mRNA with oligo(dT) does
      not yield representative samples of cDNA.

PMID- 12177352
TI  - The cold-inducible icl gene encoding thermolabile isocitrate lyase of a
      psychrophilic bacterium, Colwellia maris.
AB  - The gene encoding isocitrate lyase (ICL; EC 4.1.3.1) of a psychrophilic
      bacterium, Colwellia maris, was cloned and sequenced. The ORF of the gene (icl)
      was 1584 bp long, and the predicted gene product consisted of 528 aa (molecular
      mass 58150 Da) and showed low homology with the corresponding enzymes from other
      organisms. The analyses of amino acid content and primary structure of the C.
      maris ICL suggested that it possessed many features of a cold-adapted enzyme.
      Primer extension and Northern blot analyses revealed that two species of the icl
      mRNAs with differential lengths of 5'-untranslated regions (TS1 and TS2) were
      present, of which the 5' end (TS1 and TS2 sites) were G and A, located at 130 and
      39 bases upstream of the translation start codon, respectively. The levels of TS1
      and TS2 mRNAs were increased by both acetate and low temperature. The induction
      of icl expression by low temperature took place in the C. maris cells grown on
      succinate as the carbon source but not acetate. Furthermore, a similar manner of
      inductions was also found in the levels of the translation and the enzyme
      activity in cell-free extract. These results suggest that the icl gene, encoding
      thermolabile isocitrate lyase, of C. maris is important for acetate utilization
      and cold adaptation.

PMID- 12177353
TI  - Identification and characterization of novel small RNAs in the aspS-yrvM
      intergenic region of the Bacillus subtilis genome.
AB  - A novel RNA species was isolated from Bacillus subtilis, and its sequence was
      determined and mapped to its genetic position. This RNA was termed BS190 RNA from
      the length of its mature form (190 nt), and the gene encoding it is located
      within the aspS-yrvM intergenic region of the B. subtilis genome. Northern
      blotting revealed that the novel RNA species is transcribed in vegetative cells
      as a larger precursor (BS201 RNA, 201 nt). After transcription, the 5' end of the
      precursor is processed to generate the mature form, BS190 RNA. A computer-aided
      prediction of the secondary structure of BS190 RNA showed that it can be folded
      into a single hairpin structure with some bulge structures. The authors found
      that the growth rate of a DeltaBS190 mutant strain of B. subtilis was reduced
      when compared to the wild-type. A phylogenetic comparison of the sequence of the
      BS190 RNA gene with sequences from the databases suggests that RNA related to
      BS190 RNA appears to be encoded in the genomes of Bacillus halodurans and
      Listeria monocytogenes.

PMID- 12177354
TI  - Protective role of trehalose during severe oxidative stress caused by hydrogen
      peroxide and the adaptive oxidative stress response in Candida albicans.
AB  - The cellular response to the oxidative stress caused by hydrogen peroxide and its
      putative correlation with the stress protector trehalose was investigated in
      Candida albicans CAI.4 and the tps1/tps1 double mutant, which is deficient in
      trehalose synthesis. When exponential wild-type blastoconidia were exposed to
      high concentrations of hydrogen peroxide, they displayed a high cell survival,
      accompanied by a marked rise of intracellular trehalose. The latter is due to a
      moderate activation of trehalose synthase and the concomitant inactivation of
      neutral trehalase. Identical challenge in the tps1/tps1 double mutant severely
      reduced cell viability, a phenotype which was suppressed by overexpression of the
      TPS1 gene. Pretreatment of growing cultures from both strains with either a low,
      non-lethal concentration of H(2)O(2) (0.5 mM) or a preincubation at 37 degrees C,
      induced an adaptive response that protected cells from being killed by a
      subsequent exposure to oxidative stress. During these mild oxidative
      preincubations, trehalose was not induced in CAI.4 cells and remained
      undetectable in their tps1/tps1 counterpart. Blastoconidia from the two strains
      exhibited a similar degree of cell protection during the adaptive response. The
      induction of trehalose accumulation by H(2)O(2) was not due to an increased
      expression of TPS1 mRNA. These results are consistent with a mainly protective
      role of trehalose in C. albicans during direct oxidative stress but not during
      acquired oxidative tolerance.

PMID- 12177355
TI  - A PCR-based strategy to generate integrative targeting alleles with large regions
      of homology.
AB  - Cryptococcus neoformans is an opportunistic fungal pathogen with a defined sexual
      cycle for which genetic and molecular techniques are well developed. The entire
      genome sequence of one C. neoformans strain is nearing completion. The efficient
      use of this sequence is dependent upon the development of methods to perform more
      rapid genetic analysis including gene-disruption techniques. A modified PCR
      overlap technique to generate targeting constructs for gene disruption that
      contain large regions of gene homology is described. This technique was used to
      disrupt or delete more than a dozen genes with efficiencies comparable to those
      previously reported using cloning technology to generate targeting constructs.
      Moreover, it is shown that disruptions can be made using this technique in a
      variety of strain backgrounds, including the pathogenic serotype A isolate H99
      and recently characterized stable diploid strains. In combination with the
      availability of the complete genomic sequence, this gene-disruption technique
      should pave the way for higher throughput genetic analysis of this important
      pathogenic fungus.

PMID- 12177356
TI  - Molecular and genetic analysis of the Cryptococcus neoformans MET3 gene and a
      met3 mutant.
AB  - The Cryptococcus neoformans MET3 cDNA (encoding ATP sulfurylase) was cloned by
      complementation of the corresponding met3 mutation in Saccharomyces cerevisiae.
      Sequence analysis showed high similarity between the deduced amino acid sequence
      of the C. neoformans Met3p and other fungal ATP sulfurylases. A C. neoformans
      met3 mutant was made by targeted insertional mutagenesis, which had the expected
      auxotrophic phenotype, and reconstituted the met3 mutant to Met(+). In vitro, the
      C. neoformans met3 mutant had a substantial defect in melanin formation,
      significantly reduced growth rate, and greatly increased thermotolerance. In the
      murine inhalation infection model, the met3 mutant was avirulent and was
      deficient in its ability to survive in mice. It is concluded that, in contrast to
      the yeast form of Histoplasma capsulatum, in C. neoformans the sulfate
      assimilation arm of the methionine biosynthetic pathway plays an important role
      in vitro, even in the presence of abundant exogenous methionine, and is critical
      for virulence, and indeed for survival, in vivo.

PMID- 12177357
TI  - cAMP alteration of growth rate of Aspergillus fumigatus and Aspergillus niger is
      carbon-source dependent.
AB  - cAMP signalling has been shown to be essential for normal growth, morphology and
      virulence in fungal pathogens of both plants and animals. The effects of
      exogenous cAMP on the growth of the opportunistic pathogen Aspergillus fumigatus
      were compared to those of Aspergillus niger, which has previously been
      demonstrated to respond to extracellular cAMP. Both cAMP and phosphodiesterase
      inhibitors markedly reduced the radial growth rate of A. niger after 48 h on
      minimal medium with glucose as the carbon source, whereas the growth of A.
      fumigatus was not affected by cAMP. However, when glycerol, which does not
      initiate carbon catabolite repression, was used as a carbon source, cAMP
      inhibited the radial growth rate of only A. fumigatus (P<0.05). The addition of
      cAMP to glycerol-minimal medium resulted in a fourfold increase in protein kinase
      A activity in A. fumigatus cell extracts when compared with pre-treatment
      samples. The protein kinase A activity in A. fumigatus cell extracts from
      cultures grown in glucose did not change significantly with the addition of cAMP.
      These studies demonstrate that although the growth rates of both A. fumigatus and
      A. niger are sensitive to the addition of exogenous cAMP, the response of each
      organism is distinct and dependent on the carbon source used.

PMID- 12177358
TI  - Cyclic AMP-dependent protein kinase is involved in morphogenesis of Aspergillus
      niger.
AB  - The cAMP signal transduction pathway controls many processes in fungi. The pkaR
      gene, encoding the regulatory subunit (PKA-R) of cAMP-dependent protein kinase
      (PKA), was cloned from the industrially important filamentous fungus Aspergillus
      niger. To investigate the involvement of PKA in morphology of A. niger, a set of
      transformants which overexpressed pkaR or pkaC (encoding the catalytic subunit of
      PKA) either individually or simultaneously was prepared as well as mutants in
      which pkaR and/or pkaC were disrupted. Strains overexpressing pkaR or both pkaC
      and pkaR could not be distinguished from the wild-type, suggesting that
      regulation of PKA activity is normal in these strains. Absence of PKA activity
      resulted in a two- to threefold reduction in colony diameter on plates. The most
      severe phenotype was observed in the absence of PKA-R, i.e., very small colonies
      on plates, absence of sporulation and complete loss of growth polarity during
      submerged growth. Suppressor mutations easily developed in the DeltapkaR mutant
      and one of these mutants appeared to lack PKA-C activity. These data suggest that
      cAMP-dependent protein phosphorylation in A. niger regulates growth polarity and
      formation of conidiospores.

PMID- 12177359
TI  - Medusa's head in bloody CSF.

PMID- 12177360
TI  - Potassium depletion as a risk factor for stroke: will a banana a day keep your
      stroke away?

PMID- 12177361
TI  - Genes, brainstem development, and eye movements.

PMID- 12177362
TI  - Serum potassium level and dietary potassium intake as risk factors for stroke.
AB  - BACKGROUND: Numerous studies have found that low potassium intake and low serum
      potassium are associated with increased stroke mortality, but data regarding
      stroke incidence have been limited. Serum potassium levels, dietary potassium
      intake, and diuretic use in relation to risk for stroke in a prospectively
      studied cohort were investigated. METHODS: The study comprised 5,600 men and
      women older than 65 years who were free of stroke at enrollment. Baseline data
      included serum potassium level, dietary potassium intake, and diuretic use.
      Participants were followed for 4 to 8 years, and the incidence and types of
      strokes were recorded. Low serum potassium was defined as less than 4.1 mEq/L,
      and low potassium intake as less than 2.4 g/d. RESULTS: Among diuretic users,
      there was an increased risk for stroke associated with lower serum potassium
      (relative risk [RR]: 2.5, p < 0.0001). Among individuals not taking diuretics,
      there was an increased risk for stroke associated with low dietary potassium
      intake (RR: 1.5, p < 0.005). The small number of diuretic users with lower serum
      potassium and atrial fibrillation had a 10-fold greater risk for stroke compared
      with those with higher serum potassium and normal sinus rhythm. CONCLUSIONS: A
      lower serum potassium level in diuretic users, and low potassium intake in those
      not taking diuretics were associated with increased stroke incidence among older
      individuals. Lower serum potassium was associated with a particularly high risk
      for stroke in the small number of diuretic users with atrial fibrillation.
      Further study is required to determine if modification of these factors would
      prevent strokes.

PMID- 12177363
TI  - Patterns of cerebral blood flow reduction in patients with ischemic
      leukoaraiosis.
AB  - BACKGROUND: Ischemic leukoaraiosis (ILA) refers to diffuse T2-weighted white
      matter hyperintensity in the context of a previous clinical lacunar stroke.
      Reduced cerebral blood flow (CBF) in white matter has been demonstrated, but it
      is not known whether hypoperfusion is confined to lesions or extends into normal
      appearing white matter. Demonstrating changes in normal-appearing white matter
      would provide clues to the importance of hypoperfusion in pathogenesis and would
      be an obvious target for therapies aimed at restoring white matter blood flow.
      METHODS: Twenty-one patients with ILA, and 16 age-matched control subjects,
      underwent exogenous contrast-based quantitative perfusion MRI. CBF was determined
      both within and outside areas of T2-weighted hyperintensity in both
      periventricular white matter and the centrum semiovale. RESULTS: CBF of normal
      appearing white matter was reduced in periventricular regions (for patients with
      ILA, 17.9 +/- 5.6 mL/100 g/min; for controls, 21.6 +/- 5.1 mL/100 g/min; p =
      0.046). CBF in gray matter and normal-appearing white matter of the centrum
      semiovale did not differ significantly between groups. In normal-appearing white
      matter in patients, CBF was higher in the centrum semiovale than periventricular
      white matter, with a similar trend in control subjects. CONCLUSIONS:
      Hypoperfusion may be an early feature in the development of periventricular
      lesions in ILA and may play a direct pathogenic role. Serial studies are now
      needed to determine whether these changes herald the appearance of new lesions
      and represent "at risk" white matter, and to determine whether pharmacological
      agents can restore perfusion of normal-appearing white matter.

PMID- 12177364
TI  - Anthrax meningoencephalitis.
AB  - OBJECTIVE: To review reported cases of anthrax meningoencephalitis and describe
      the clinical findings, diagnostic test results, treatment, and outcome over the
      past 50 years. METHODS: Retrospective review of English language articles
      published since Haight's (1952) review. RESULTS: Thirty-four core articles were
      identified, describing 70 patients with cutaneous (29%), gastrointestinal (17%),
      inhalational (39%), and unknown (16%) sources of infection. Clinical signs on
      presentation included fever, malaise, meningeal signs, hyperreflexia, and
      delirium, stupor, or coma. CSF analyses demonstrated hemorrhagic meningitis, with
      positive Gram's stains and CSF cultures. Many patients presented in extremis
      following a prodromal period of 1 to 6 days, and 75% died within 24 hours of
      presentation. Despite aggressive treatment in many cases, only 6% (4 of 70)
      survived, none of whom had pulmonary anthrax. Surviving patients generally had a
      cutaneous portal of entry, were younger, and had less severely abnormal initial
      CSF results than patients who died. Most of the survivors recovered fully.
      Pathologic findings included hemorrhagic meningitis, multifocal subarachnoid and
      intraparenchymal hemorrhages, vasculitis, and cerebral edema. CONCLUSIONS:
      Anthrax meningoencephalitis has a high case-fatality rate, even with aggressive
      antibiotic treatment and supportive therapy. Hemorrhagic meningitis should raise
      suspicion of anthrax infection, particularly if gram-positive rods are
      demonstrated on Gram's stain. Anthrax meningoencephalitis can develop from any
      primary focus, but survival appears to be most likely if meningoencephalitis
      develops from cutaneous anthrax. Treatment of surviving patients was generally
      begun before signs and symptoms of meningoencephalitis were present.

PMID- 12177365
TI  - Normalization of T2 signal abnormalities in hemispheric white matter with liver
      transplant.
AB  - OBJECTIVE: To determine whether edema can be assessed by MRI using T2-weighted
      signal intensity of hemispheric white matter in cirrhotic patients. METHODS: Fast
      FLAIR and magnetization transfer images were obtained before (24) and after (11)
      liver transplantation. T2-weighted abnormalities on baseline scans and their time
      course changes were analyzed and compared with MT ratios (MTR). RESULTS: Fast
      FLAIR baseline images showed faint to substantial, bilateral, symmetric increased
      signal intensity along the hemispheric white matter in or around the
      corticospinal tract in 23/24 patients. After liver transplantation the signal
      abnormalities gradually recovered. This gradual decrease in signal intensity
      correlated with an increase in MTR values. CONCLUSION: Asymptomatic symmetric
      high-signal intensity in the hemispheric white matter on fast-FLAIR MR images is
      present in cirrhosis. Normalization of this finding after successful liver
      transplantation and its correlation with MTR values suggest that this signal
      abnormality reflects mild edema.

PMID- 12177366
TI  - Correlates of independent HIV-1 replication in the CNS and of its control by
      antiretrovirals.
AB  - OBJECTIVE: To investigate in detail factors associated with independent
      replication of HIV-1 in CNS, and to predict its therapeutic control. METHODS: HIV
      RNA concentration was measured by PCR in 134 cross-sectional paired plasma and
      CSF samples from 95 patients infected with HIV-1 with various conditions, and in
      longitudinal CSF samples from 50 patients on antiretroviral treatment. Monocyte
      chemotactic protein (MCP)-1 was quantified in CSF by ELISA. RESULTS: High HIV RNA
      levels either in plasma or in CSF did not correlate with HIV RNA concentration in
      the paired biologic sample. A high CSF-to-plasma HIV RNA ratio, suggesting
      independent viral replication in the CNS, was associated with higher CSF viral
      load and higher CSF MCP-1 levels. Higher MCP-1 levels in the CSF were also
      associated with neurologic disorders and were not influenced by the use of highly
      active antiretroviral therapy (HAART). A higher number of antiretroviral drugs
      with CSF penetration correlated with a more profound CSF HIV-1 load reduction,
      independently from the use of HAART alone. Virologic suppression in CSF was
      predicted by a higher number of CSF-penetrating antiretrovirals and by the
      baseline CSF viral load, whereas lower baseline CD4 counts and higher MCP-1
      levels were associated with increased risk of virologic failure. CONCLUSIONS:
      Quantification of HIV RNA in CSF is clinically useful, particularly in patients
      with neurologic disorders. CSF penetration of antiretrovirals must be considered
      when choosing treatments, mainly in patients with higher CSF viral loads,
      advanced disease, and CNS disorders associated with significant macrophage
      activation.

PMID- 12177367
TI  - X-linked myoclonic epilepsy with spasticity and intellectual disability: mutation
      in the homeobox gene ARX.
AB  - OBJECTIVE: To describe a new syndrome of X-linked myoclonic epilepsy with
      generalized spasticity and intellectual disability (XMESID) and identify the gene
      defect underlying this disorder. METHODS: The authors studied a family in which
      six boys over two generations had intractable seizures using a validated seizure
      questionnaire, clinical examination, and EEG studies. Previous records and
      investigations were obtained. Information on seizure disorders was obtained on
      271 members of the extended family. Molecular genetic analysis included linkage
      studies and mutational analysis using a positional candidate gene approach.
      RESULTS: All six affected boys had myoclonic seizures and TCS; two had infantile
      spasms, but only one had hypsarrhythmia. EEG studies show diffuse background
      slowing with slow generalized spike wave activity. All affected boys had moderate
      to profound intellectual disability. Hyperreflexia was observed in obligate
      carrier women. A late-onset progressive spastic ataxia in the matriarch raises
      the possibility of late clinical manifestations in obligate carriers. The
      disorder was mapped to Xp11.2-22.2 with a maximum lod score of 1.8. As recently
      reported, a missense mutation (1058C>T/P353L) was identified within the
      homeodomain of the novel human Aristaless related homeobox gene (ARX).
      CONCLUSIONS: XMESID is a rare X-linked recessive myoclonic epilepsy with
      spasticity and intellectual disability in boys. Hyperreflexia is found in carrier
      women. XMESID is associated with a missense mutation in ARX. This disorder is
      allelic with X-linked infantile spasms (ISSX; MIM 308350) where polyalanine tract
      expansions are the commonly observed molecular defect. Mutations of ARX are
      associated with a wide range of phenotypes; functional studies in the future may
      lend insights to the neurobiology of myoclonic seizures and infantile spasms.

PMID- 12177368
TI  - Knowledge of the human body: a distinct semantic domain.
AB  - BACKGROUND: Patients with selective deficits in the naming and comprehension of
      animals, plants, and artifacts have been reported. These descriptions of specific
      semantic category deficits have contributed substantially to the understanding of
      the architecture of semantic representations. OBJECTIVE: This study sought to
      further understanding of the organization of the semantic system by demonstrating
      that another semantic category, knowledge of the human body, may be selectively
      preserved. METHODS: The performance of a patient with semantic dementia was
      compared with the performance of healthy controls on a variety of tasks assessing
      distinct types of body representations, including the body schema, body image,
      and body structural description. RESULTS: Despite substantial deficits on tasks
      involving language and knowledge of the world generally, the patient performed
      normally on all tests of body knowledge except body part naming; even in this
      naming task, however, her performance with body parts was significantly better
      than on artifacts. CONCLUSIONS: The demonstration that body knowledge may be
      preserved despite substantial semantic deficits involving other types of semantic
      information argues that body knowledge is a distinct and dissociable semantic
      category. These data are interpreted as support for a model of semantics that
      proposes that knowledge is distributed across different cortical regions
      reflecting the manner in which the information was acquired.

PMID- 12177369
TI  - Depressive symptoms, cognitive decline, and risk of AD in older persons.
AB  - BACKGROUND: Cross-sectional and retrospective case-control studies suggest an
      association of depression symptoms with cognitive impairment and AD, but there
      have been few prospective studies and their results have been inconsistent.
      METHODS: Participants are Catholic clergy members who were aged > or =65 years
      and who did not have clinical evidence of AD. During a 7-year period, they
      underwent annual clinical evaluations that included clinical classification of AD
      and detailed cognitive function testing from which global and specific measures
      of cognition were derived. Number of depressive symptoms was assessed at baseline
      with a modified, 10-item Center for Epidemiologic Studies Depression Scale (CES
      D). The association of CES-D score with incident AD, using proportional hazards
      models, and cognitive decline, using random effects models, was examined.
      RESULTS: At baseline, participants reported an average of about one depressive
      symptom on the CES-D scale (range, 0 to 8). During the 7 years of follow-up, 108
      persons developed AD. In analyses that controlled for selected demographic and
      clinical variables including baseline level of cognitive function, CES-D score
      was associated with both risk of AD and rate of cognitive decline. For each
      depressive symptom, risk of developing AD increased by an average of 19%, and
      annual decline on a global cognitive measure increased by an average of 24%.
      CONCLUSIONS: The results raise the possibility that depressive symptoms in older
      persons may be associated with risk of developing AD.

PMID- 12177370
TI  - Interleukin-6 and risk of cognitive decline: MacArthur studies of successful
      aging.
AB  - OBJECTIVE: To investigate whether plasma interleukin-6 (IL-6) is cross
      sectionally related to poorer cognitive function and whether a baseline plasma IL
      6 measurement can predict risk for decline in cognitive function in longitudinal
      follow-up of a population-based sample of nondisabled elderly people. METHODS: A
      prospective cohort study of 779 high-functioning men and women aged 70 to 79 from
      the MacArthur Study of Successful Aging was conducted. Regression modeling was
      used to investigate whether baseline IL-6 levels (classified by tertiles) were
      associated with initial cognitive function and whether IL-6 levels predicted
      subsequent declines in cognitive function from 1988 to 1991 (2.5-year follow-up)
      and from 1988 to 1995 (7-year follow-up). RESULTS: Subjects in the highest
      tertile for plasma IL-6 were marginally more likely to exhibit poorer baseline
      cognitive function (i.e., scores below the median), independent of demographic
      status, social status, health and health behaviors, and other physiologic
      variables (odds ratio [OR] = 1.46; 95% CI: 0.97, 2.20). At 2.5 years, those in
      both the second tertile of IL-6 (OR = 2.21; 95% CI: 1.44, 3.42) and the third
      tertile (OR = 2.03; 95% CI: 1.30, 3.19) were at increased risk of cognitive
      decline even after adjusting for all confounders. At 7 years of follow-up, only
      those in the highest IL-6 tertile were significantly more likely to exhibit
      declines in cognition (OR = 1.90; 95% CI: 1.14, 3.18) after adjustment for all
      confounders. CONCLUSIONS: The results suggest a relationship between elevated
      baseline plasma IL-6 and risk for subsequent decline in cognitive function. These
      findings are consistent with the hypothesized relationship between brain
      inflammation, as measured here by elevated plasma IL-6, and neuropathologic
      disorders.

PMID- 12177371
TI  - Brain function and cognition in a community sample of elderly Latinos.
AB  - BACKGROUND: Previous studies using PET to measure cerebral glucose metabolism in
      AD have found metabolic reductions in the temporoparietal and posterior cingulate
      cortices in individuals with dementia and those at risk of developing it. This
      study was designed to extend this finding to individuals selected from a
      population-based cohort of Mexican Americans with a wide spectrum of cognitive
      ability. METHODS: A group of 93 individuals was selected from the Sacramento Area
      Latino Study on Aging, and subjects were categorized into four groups of
      increasing levels of cognitive impairment: normal, memory impaired, cognitively
      impaired but not demented (CIND), and demented. PET was performed with the tracer
      [(18)F]-fluorodeoxyglucose, and data were analyzed with both statistical
      parametric mapping and an atrophy-corrected volume of interest approach. RESULTS:
      Individuals with dementia had metabolic reductions that were most robust in the
      posterior cingulate cortex, whereas CIND subjects had less statistically robust
      reductions in the posterior cingulate cortex. Cingulate hypometabolism increased
      the risk of dementia and was a significant risk factor for dementia in logistic
      regression models that also incorporated MR measures of hippocampal volume and
      white matter hyperintensities. CONCLUSION: Posterior cingulate cortical
      hypometabolism is clearly detected in individuals with dementia who are selected
      from a population with lower education and a high prevalence of cerebrovascular
      risk factors, supporting the generalizability of this finding. These metabolic
      reductions occur prior to the onset of dementia but only in those persons with
      relatively advanced symptoms.

PMID- 12177372
TI  - Brain structure and cognition in a community sample of elderly Latinos.
AB  - BACKGROUND: Previous studies have found that hippocampal atrophy and white matter
      hyperintensities (WMH) on MRI are linked to cognitive impairment and dementia.
      The authors measured these variables in a population-based cohort of older
      Mexican Americans with a wide spectrum of cognitive ability, ranging from normal
      cognition to dementia. OBJECTIVE: To investigate whether these structural brain
      changes were seen in individuals prior to the development of dementia and how
      these changes were related to the presence of dementia. METHODS: A sample of 122
      subjects was selected from the Sacramento Area Latino Study on Aging, and
      subjects were categorized into four groups of increasing levels of cognitive
      impairment: normal, memory impaired (MI), cognitively impaired but not demented
      (CIND), and demented. Hippocampal volume was quantified using a region of
      interest approach. WMH was rated on a semiquantitative scale as the percent of
      total volume of white matter. RESULTS: Hippocampal volume was significantly
      reduced in CIND and demented individuals, and WMH were significantly increased in
      demented subjects. MI subjects did not have any significant changes in
      hippocampal volume or WMH. The risk for developing dementia was significantly and
      comparably increased in subjects with either hippocampal atrophy or high WMH.
      However, the risk for dementia increased dramatically in subjects with both
      hippocampal atrophy and a high degree of WMH. CONCLUSION: Reductions in
      hippocampal volume may be present before dementia but not until cognitive
      impairment is relatively severe. Because there is a synergistic effect between
      high WMH and hippocampal atrophy, interactions between vascular and degenerative
      processes may be important determinants of dementia.

PMID- 12177373
TI  - Noninvasive in vivo assessment of cholinergic cortical circuits in AD using
      transcranial magnetic stimulation.
AB  - BACKGROUND: A recently devised test of motor cortex excitability (short latency
      afferent inhibition) was shown to be sensitive to the blockade of muscarinic
      acetylcholine receptors in healthy subjects. The authors used this test to assess
      cholinergic transmission in the motor cortex of patients with AD. METHODS: The
      authors evaluated short latency afferent inhibition in 15 patients with AD and
      compared the data with those of 12 age-matched healthy controls. RESULTS:
      Afferent inhibition was reduced in the patients (mean responses +/- SD reduced to
      85.7% +/- 15.8% of the test size) compared with controls (mean responses +/- SD
      reduced to 45.3% +/- 16.2% of the test size; p < 0.001, unpaired t-test).
      Administration of a single oral dose of rivastigmine improved afferent inhibition
      in a subgroup of six patients. CONCLUSIONS: The findings suggest that this method
      can be used as a noninvasive test of cholinergic pathways in AD. Future studies
      are required to evaluate whether short latency afferent inhibition measurements
      have any consistent clinical correlates.

PMID- 12177374
TI  - Nonoverlapping but synergetic tau and APP pathologies in sporadic Alzheimer's
      disease.
AB  - OBJECTIVE: To determine the spatiotemporal mapping of tau pathologies and
      insoluble pools of Abeta in aging and sporadic AD, and their contribution to the
      physiopathologic, clinical, and neuropathologic features. METHODS: The authors
      studied 130 patients of various ages and different cognitive status, from
      nondemented controls (n = 60) to patients with severe definite AD (n = 70) who
      were followed prospectively. Insoluble Abeta 42 and 40 species were fully
      solubilized and quantified in the main neocortical areas, with a new procedure
      adapted to human brain tissue. Tau pathology staging was determined in 10
      different brain areas, using Western blots. RESULTS: In AD, there is a
      constellation of amyloid phenotypes, extending from cases with exclusively
      aggregated Abeta 42 to cases with, in addition, large quantities of insoluble
      Abeta 40 species. Five other points were observed: 1) There was no spatial and
      temporal overlap in the distribution of these two insoluble Abeta species in
      cortical brain areas. 2) In contrast to solubilized Abeta 40 aggregates composed
      essentially of monomers and dimers, solubilized Abeta 42 was essentially observed
      as dimers and multimers. 3) Abeta 42 aggregates were observed at the early stages
      of tau pathology, whereas the insoluble Abeta 40 pool was found at the last
      stages. 4) During the progression of the disease, Abeta aggregates increase in
      quantity and heterogeneity, in close parallel to the extension of tau pathology.
      5) There was no spatial overlap between Abeta aggregation that is widespread and
      heterogeneously distributed in cortical areas and tau pathology that is
      progressing sequentially, stereotypically, and hierarchically. CONCLUSIONS: These
      observations demonstrate that Abeta 42 aggregation, and not Abeta 40, is the
      marker that is close to Alzheimer etiology. It should be the main target for the
      early biological diagnosis of AD and modeling. Furthermore, the spatial mismatch
      between amyloid ss-precursor protein (APP) and tau pathologies in cortical brain
      areas demonstrates that neurodegeneration is not a direct consequence of
      extracellular Abeta neurotoxicity. Hence, there is a synergetic effect of APP
      dysfunction, revealed by Abeta aggregation, on the neuron-to-neuron propagation
      of tau pathology.

PMID- 12177375
TI  - Nonmotor fluctuations in Parkinson's disease: frequent and disabling.
AB  - OBJECTIVE: To assess the frequency and disability caused by nonmotor fluctuations
      (NMF) in PD. METHODS: A structured questionnaire was administered to 50 patients
      with PD with motor fluctuations (MF), focused on 54 nonmotor symptoms classified
      in three subgroups: 26 dysautonomic, 21 cognitive and psychiatric, and seven
      pain/sensory NMF. The link between each NMF and the motor state was determined.
      Patients were asked to grade their disability from 0 (no disability) to 4
      (maximum discomfort) and to specify which kind of fluctuation subgroup (motor or
      nonmotor) was the most incapacitating. A statistical analysis was performed to
      determine the frequency of each NMF and to determine whether the level of
      disability resulting from NMF could be correlated to the main characteristics of
      the population. RESULTS: All patients had had at least one type of NMF, most of
      which were associated with the "off" state. Anxiety (66%), drenching sweats
      (64%), slowness of thinking (58%), fatigue (56%), and akathisia (54%) were the
      most frequent NMF. Some symptoms such as anxiety or dyspnea correlated with a
      greater level of disability. The total number of NMF was found to be correlated
      with the motor disability. Incapacity resulting from the dysautonomic
      fluctuations was also significantly correlated with levodopa treatment.
      Surprisingly, 28% of the patients stated that NMF involved a greater degree of
      disability than MF. CONCLUSION: Nonmotor fluctuations are frequent and
      debilitating in PD.

PMID- 12177376
TI  - The behavioral spectrum of tic disorders: a community-based study.
AB  - BACKGROUND: Tourette syndrome (TS) and related tic disorders are commonly
      associated with obsessive-compulsive disorder (OCD) and attention deficit
      hyperactivity disorder (ADHD). It has been argued, however, that any observed
      association between TS and these and other psychopathologies may be due to
      ascertainment bias in that individuals with multiple problems are more likely to
      be referred for medical evaluation. METHODS: In order to overcome the potential
      confounding by ascertainment bias, the authors conducted a community-based study
      of school children using direct interviews to determine the prevalence of tic
      disorders and any comorbid psychopathology. A standard psychiatric interview and
      standardized rating scales were utilized to diagnose childhood behavioral
      disorders. RESULTS: Of the 1,596 children interviewed, 339 were identified as
      having tics. The following psychopathologies were found more commonly (p < 0.05)
      in the children with tics: OCD, ADHD, separation anxiety, overanxious disorder,
      simple phobia, social phobia, agoraphobia, mania, major depression, and
      oppositional defiant behavior. CONCLUSION: The behavioral spectrum of tic
      disorders includes OCD, other anxiety disorders, a mood disorder, and attention
      deficit and disruptive behavior disorders.

PMID- 12177377
TI  - Electrodiagnosis of ulnar neuropathy at the wrist: conduction block versus
      traditional tests.
AB  - BACKGROUND: Compared to ulnar neuropathy at the elbow (UNE), ulnar neuropathy at
      the wrist (UNW) is rarer and more difficult to localize with routine
      electrophysiologic studies. METHODS: By stimulating the ulnar nerve at the wrist
      and palm, and recording from first dorsal interosseous (FDI), the sensitivity and
      specificity of conduction block (CB) and slow conduction velocity (CV) of FDI
      fibers across the wrist was compared to traditional electrodiagnostic techniques
      for localization of UNW. Twenty patients with clinically defined UNW (due mainly
      to wrist trauma), 30 normal controls, and 20 disease controls with severe (n =
      10) and mild (n = 10) UNE were evaluated prospectively. The upper (mean +2.5 SD)
      and lower (mean -2.5 SD) limits for all measurements were derived from the normal
      controls. RESULTS: The UNW patients showed: slow wrist-palm FDI CV (<37 m/s) in
      16 (80%); definite or probable CB in 14 (70%); prolonged distal latency (DL) to
      FDI (>4.5 milliseconds) in 12 (60%), to ulnar-innervated palmar interosseous (PI)
      versus median-innervated lumbrical (L) in 12 (60%), and to abductor digiti minimi
      (ADM) in 11 (55%). However, only CB and slow wrist-palm FDI CV (<37 m/s) were
      specific for UNW; prolonged DL to FDI was found in 4 patients (40%), to ADM in 4
      patients (40%), and to PI in 1 patient (10%) with severe UNE. Overall, CB or slow
      wrist-palm FDI CV was present in 19 patients with UNW (95%). EMG failed to
      differentiate UNW from UNE, because forearm ulnar-innervated muscles were
      typically normal in UNW, but also often normal in mild UNE. CONCLUSIONS: In UNW,
      an additional palmar stimulation site improves electrodiagnostic yield, and
      demonstrates that CB is an important cause of muscle weakness.

PMID- 12177378
TI  - The final month of life in patients with ALS.
AB  - OBJECTIVE: To study the health care experiences and palliative care needs of
      patients with ALS in their final month of life. METHODS: Caregivers of decedent
      patients with ALS completed a single survey focused on the final month of life.
      They reported the patients' physical and emotional symptoms, preferences for end
      of-life care, completion of advance directives, and preparation for death. The
      caregiver reported which life-sustaining treatments were administered, withheld,
      or withdrawn; whether the patient was enrolled in hospice; and their own
      satisfaction with the patient's medical care. RESULTS: Fifty caregivers completed
      the survey. Caregivers reported that the most common symptoms in the last month
      of life included difficulty communicating (62%), dyspnea (56%), insomnia (42%),
      and discomfort other than pain (48%). Pain was both frequent and severe. One
      third of caregivers were dissatisfied with some aspect of symptom management.
      Caregivers reported an advance directive was completed by 88% of patients and the
      patients' goals of care were honored by 88% of health care practitioners. Two
      thirds of patients were enrolled in hospice. Compared to nonhospice patients,
      hospice patients were significantly more likely to: 1) die in their preferred
      location; 2) die outside the hospital; and 3) receive morphine. Most caregivers
      reported that their loved one was at peace, and prepared for and was accepting of
      death. CONCLUSIONS: Caregivers report that many patients with ALS still
      experience distressing physical symptoms in the last month of life, despite
      enrollment in hospice. Most patients with ALS, however, anticipate and plan for
      their deaths and have their wishes respected.

PMID- 12177379
TI  - Familial horizontal gaze palsy with progressive scoliosis maps to chromosome
      11q23-25.
AB  - Horizontal gaze palsy with progressive scoliosis (HGPS) is a rare, autosomal
      recessive disorder characterized by a congenital absence of conjugate horizontal
      eye movement, with progressive scoliosis developing in childhood or adolescence.
      The authors identified two unrelated consanguineous families with HGPS.
      Genomewide homozygosity mapping and linkage analysis mapped the disease locus to
      a 30-cM interval on chromosome 11q23-25 (combined maximum multipoint lod score Z
      = 5.46).

PMID- 12177380
TI  - Migraine and the risk of cervical artery dissection: a case-control study.
AB  - The association between migraine and cervical artery dissection (CAD) was
      explored in a hospital-based case-control study. Migraine was present in 49.1%
      (23/47) of patients with CAD and in 21% (11/52) of patients hospitalized for a
      cerebral ischemic event not related to a CAD (adjusted odds ratio = 3.6; 1.5 to
      8.6, p = 0.005). This result supports the hypothesis that an underlying arterial
      wall disease could be a predisposing condition for migraine.

PMID- 12177381
TI  - Multiple risk factors in neonatal sinovenous thrombosis.
AB  - The etiology of neonatal sinovenous thrombosis is poorly understood. The authors
      report the risk factors and radiologic features of neonatal sinovenous thrombosis
      seen over an 11-year period. Of 30 patients, 29% received extracorporeal membrane
      oxygenation treatment, and 23% had congenital heart disease. Genetic
      thrombophilias were present in four of the seven infants tested. Eighteen
      neonates had multiple maternal, neonatal, perinatal, or prothrombotic
      complications. Sinovenous thrombosis was often accompanied by infarction (50%) or
      intraventricular hemorrhage (33%).

PMID- 12177382
TI  - Dissociated crossed aphasia: a challenging language representation disorder.
AB  - A monolingual strongly right-handed woman developed a left hemiparesis and severe
      motor aphasia following a right middle cerebral artery infraction, whereas
      comprehension was entirely intact. She had a history of a transient
      cerebrovascular event characterized by right hemiparesis and fluent sensory
      aphasia. This case suggests a transhemispheric pattern of language organization
      in which the Broca area resides in the right hemisphere, whereas the Wernicke
      area is in the left.

PMID- 12177383
TI  - Analysis of tau haplotypes in Pick's disease.
AB  - Pick's disease (PiD) is characterized by the deposition of tau protein as three
      repeat tau Pick bodies, whereas progressive supranuclear palsy (PSP) involves the
      deposition of four-repeat tau neurofibrillary tangles. PSP is associated with the
      tau H1 haplotype. The authors investigated a possible association between PiD and
      the tau H1 or H2 haplotype. There was no difference between the tau H2 haplotype
      or H2H2 genotype frequency in PiD cases and control subjects. No tau mutations
      were identified in pathologically typical cases of PiD, with antibody 12-E8
      negative Pick bodies.

PMID- 12177384
TI  - Dopamine transmission in DYT1 dystonia: a biochemical and autoradiographical
      study.
AB  - Indices of dopamine transmission were measured in the postmortem striatum of DYT1
      dystonia brains. A significant increase in the striatal 3,4-dihydroxyphenylacetic
      acid/dopamine ratio was found. Quantitative autoradiography revealed no
      differences in the density of dopamine transporter or vesicular monoamine
      transporter-2 binding; however, there was a trend toward a reduction in D(1)
      receptor and D(2) receptor binding. One brain with DYT1 parkinsonism was
      similarly evaluated and marked reductions in striatal dopamine, 3,4
      dihydroxyphenylacetic acid, and homovanillic acid content as well as the density
      of binding of all four dopaminergic ligands were measured.

PMID- 12177386
TI  - Distal myopathy with rimmed vacuoles: novel mutations in the GNE gene.
AB  - The authors present three novel missense mutations in the UDP-N-acetylglucosamine
      2-epimerase/N-acetylmannosamine kinase (GNE) gene, the causative gene for
      hereditary inclusion body myopathy, in Japanese patients with distal myopathy
      with rimmed vacuoles. Seven out of nine patients had homozygous V572L mutation,
      one was a compound heterozygote with C303V and V572L mutations, and the remaining
      patient bore homozygous A631V mutation.

PMID- 12177385
TI  - Increased brainstem excitability in stiff-person syndrome.
AB  - The recovery cycle of the R2 component of the blink reflex was studied in five
      patients with stiff-person syndrome (SPS) and in seven healthy control subjects.
      R2 recovery was enhanced in patients with SPS. This result is suggestive of
      hyperexcitability of brainstem interneuronal circuits in SPS. Hyperexcitability
      may result from abnormal input from suprasegmental structures or loss of
      inhibition by interneurons and is compatible with the proposal that there is a
      widespread dysfunction of central inhibitory mechanisms in SPS.

PMID- 12177387
TI  - Phenotypic variability in a Spanish family with MNGIE.
AB  - Clinical, biochemical, and genetic features of a Spanish family with
      mitochondrial neurogastrointestinal encephalomyopathy are reported. The proband
      presented with severe gastrointestinal dysmotility and the affected sister had
      extraocular muscle weakness. In both affected individuals, biochemical defects of
      thymidine phosphorylase and a pathogenic G-to-A transition mutation at nucleotide
      435 in the thymidine phosphorylase gene were identified. The first thymidine
      phosphorylase mutation identified in Spain showed phenotypic variability at
      onset.

PMID- 12177388
TI  - Neuropathologic findings in a Guillain-Barre patient with strokes after IVIg
      therapy.
AB  - Strokes have been rarely associated with immunoglobulin G (IVIg) therapy. A 70
      year-old woman with stable polycythemia vera developed Guillain-Barre syndrome
      and received IVIg, 8 days following which she became comatose due to bilaterally
      symmetric cerebral infarcts. Autopsy showed intravascular aggregates of fibrin
      IgG but also platelets and a necrotizing microangiopathy in the infarcts.

PMID- 12177389
TI  - Thunderclap headache with diplopia and anorexia.

PMID- 12177390
TI  - Brainstem hypoplasia in familial horizontal gaze palsy and scoliosis.

PMID- 12177391
TI  - Weight loss associated with vagus nerve stimulation.

PMID- 12177392
TI  - Ictal paralysis mimicking Todd's phenomenon.

PMID- 12177393
TI  - Amiodarone and acetazolamide for the treatment of genetically confirmed severe
      Andersen syndrome.

PMID- 12177394
TI  - Poem: A prodigal night.

PMID- 12177395
TI  - Brain death worldwide: accepted fact but no global consensus in diagnostic
      criteria.

PMID- 12177396
TI  - Disease modifying therapies in multiple sclerosis.

PMID- 12177397
TI  - Ethical considerations for neurologists in the management of chronic pain.

PMID- 12177398
TI  - Reversible ALS-like disorder in HIV infection. An ALS-like syndrome with new HIV
      infection and complete response to antiretroviral therapy.

PMID- 12177399
TI  - Cognitive and functional decline in African Americans with VaD, AD, and stroke
      without dementia.

PMID- 12177400
TI  - Hemicrania continua is not that rare.

PMID- 12177401
TI  - Population study of benign rolandic epilepsy: is treatment needed?

PMID- 12177402
TI  - Neurosarcoidosis.

PMID- 12177403
TI  - Neurology patient page. Depression may be another risk for Alzheimer's dementia:
      your doctor can help.

PMID- 12177404
TI  - Arizona porphyry copper/hydrothermal deposits II: crystal structure of ajoite, (K
      + Na)3Cu20Al3Si29O76(OH)16*~8H2O.
AB  - A crystal from the type locality Ajo, AZ, yielded just enough intensity from
      streaked diffractions using synchrotron x-rays at the Advanced Photon Source to
      solve the crystal structure with composition (K + Na)3Cu20Al3Si29O76(OH)16*
      approximately 8H2O; triclinic, P1, a = 13.634(5) A, b = 13.687(7), c = 14.522(7),
      alpha = 110.83(1) degrees, beta = 107.21(1), gamma = 105.68(1); refined to a
      final R = 12.5%. Electron microprobe analysis yielded a similar chemical
      composition that is slightly different from the combined chemical and electron
      microprobe analyses in the literature. The ajoite structure can be described as a
      zeolitic octahedral-tetrahedral framework that combines the alternate stacking of
      edge-sharing octahedral CuO6 layers and curved aluminosilicate layers and
      strings. Channels bounded by elliptical 12-rings and circular 8-rings of
      tetrahedra contain (K and Na) ions and water. The Al atoms occupy some of the Si
      tetrahedral sites. Each Cu atom has near-planar bonds to four oxygen atoms plus
      two longer distances that generate a distorted octahedron. Valence bond estimates
      indicate that 8 oxygen atoms of 46 are hydroxyl. Only one alkali atom was located
      in distorted octahedral coordination, and electron microprobe analyses indicate K
      and Na as major substituents. The water from chemical analysis presumably occurs
      as disordered molecules of zeolitic type not giving electron density from
      diffraction. The high R factor results from structural disorder and many weak
      intensities close to detection level. The crystal chemistry is compared with
      shattuckite, Cu5(SiO3)4(OH)2, and plancheite, Cu8Si8O22(OH)4.H2O, both found in
      oxidized copper deposits of Arizona but only the former directly with ajoite.

PMID- 12177405
TI  - FAST CARS: engineering a laser spectroscopic technique for rapid identification
      of bacterial spores.
AB  - Airborne contaminants, e.g., bacterial spores, are usually analyzed by time
      consuming microscopic, chemical, and biological assays. Current research into
      real-time laser spectroscopic detectors of such contaminants is based on e.g.,
      resonance fluorescence. The present approach derives from recent experiments in
      which atoms and molecules are prepared by one (or more) coherent laser(s) and
      probed by another set of lasers. However, generating and using maximally coherent
      oscillation in macromolecules having an enormous number of degrees of freedom is
      challenging. In particular, the short dephasing times and rapid internal
      conversion rates are major obstacles. However, adiabatic fast passage techniques
      and the ability to generate combs of phase-coherent femtosecond pulses provide
      tools for the generation and utilization of maximal quantum coherence in large
      molecules and biopolymers. We call this technique FAST CARS (femtosecond adaptive
      spectroscopic techniques for coherent anti-Stokes Raman spectroscopy), and the
      present article proposes and analyses ways in which it could be used to rapidly
      identify preselected molecules in real time.

PMID- 12177407
TI  - An improved genetic model generates high-resolution mapping of QTL for protein
      quality in maize endosperm.
AB  - The genetic mapping of polymorphic markers in a cross between two inbred plant
      lines has proven to be a powerful method for detecting quantitative trait loci
      (QTL) underlying complex traits. However, existing methods of QTL mapping were
      developed for disomic inheritance of both marker and QTL loci in a diploid
      population. To map QTL influencing traits expressed in the endosperm, a triploid
      embryo-nourishing tissue resulting from double fertilization, existing QTL
      mapping models require modification to consider the trisomic inheritance of the
      endosperm and the generation difference between the mapping population and the
      endosperm. Such a model requires simultaneous use of two successive generations,
      which theoretically can lead to an increase in resolution for QTL mapping
      compared with the use of a single backcross or F(2) generation. Using a newly
      developed model based on these considerations, we demonstrate the improved
      resolution of QTL, influencing protein quality traits in maize endosperm. The
      increased resolution made possible with this approach makes identified QTL
      accessible to positional cloning.

PMID- 12177406
TI  - The clothing effect: tactile neurons in the precentral gyrus do not respond to
      the touch of the familiar primate chair.
AB  - Neurons in a restricted zone in the precentral gyrus of macaque monkeys respond
      to tactile, visual, and auditory stimuli. The tactile receptive fields of these
      multimodal cells are usually located on the face, arm, or upper torso. In the
      present study, in awake monkeys sitting in a primate chair, the neurons responded
      to a tactile probe touching the skin within the tactile receptive field. However,
      the same neurons did not respond when the tactile receptive field was touched by
      the primate chair, to which the monkey was habituated.

PMID- 12177408
TI  - Selective impairment of reasoning about social exchange in a patient with
      bilateral limbic system damage.
AB  - Social exchange is a pervasive feature of human social life. Models in
      evolutionary biology predict that for social exchange to evolve in a species,
      individuals must be able to detect cheaters (nonreciprocators). Previous research
      suggests that humans have a cognitive mechanism specialized for detecting
      cheaters. Here we provide neurological evidence indicating that social exchange
      reasoning can be selectively impaired while reasoning about other domains is left
      intact. The patient, R.M., had extensive bilateral limbic system damage,
      affecting orbitofrontal cortex, temporal pole, and amygdala. We compared his
      performance on two types of reasoning problem that were closely matched in form
      and equally difficult for control subjects: social contract rules (of the form,
      "If you take the benefit, then you must satisfy the requirement") and precaution
      rules (of the form, "If you engage in hazardous activity X, then you must take
      precaution Y"). R.M. performed significantly worse in social contract reasoning
      than in precaution reasoning, when compared both with normal controls and with
      other brain-damaged subjects. This dissociation in reasoning performance provides
      evidence that reasoning about social exchange is a specialized and separable
      component of human social intelligence, and is consistent with other research
      indicating that the brain processes information about the social world
      differently from other types of information.

PMID- 12177409
TI  - Cross-cultural evidence of cognitive adaptations for social exchange among the
      Shiwiar of Ecuadorian Amazonia.
AB  - On the basis of evolutionary game theory, it was hypothesized that humans have an
      evolved cognitive specialization for reasoning about social exchange, including a
      subroutine for detecting cheaters. This hypothesis led to a specific prediction:
      Although humans are known to be poor at detecting potential violations of
      conditional rules in general, they should nevertheless detect them easily when
      the rule involves social exchange and looking for violations corresponds to
      looking for cheaters. This prediction was subsequently confirmed by numerous
      tests. Evolutionary analyses further predict that: (i) in humans, complex
      adaptations will be distributed in a species-typical fashion; and (ii) aspects of
      cognitive organization relevant to performing the evolved function of an
      adaptation should be more buffered against environmental and cultural variation
      than function-irrelevant aspects. Here we report experiments testing whether
      social exchange reasoning exhibits these properties of adaptations. Existing
      tests of conditional reasoning were adapted for nonliterate experimental subjects
      and were administered to Shiwiar hunter-horticulturalists of the Ecuadorian
      Amazon. As predicted, Shiwiar subjects were as highly proficient at cheater
      detection as subjects from developed nations. Indeed, the frequency of cheater
      relevant choices among Shiwiar hunter-horticulturalists was indistinguishable
      from that of Harvard undergraduates. Also as predicted, cultural variation was
      confined to those aspects of reasoning that are irrelevant to social exchange
      algorithms functioning as an evolutionarily stable strategy. Finally, Shiwiar
      subjects displayed the same low performance on descriptive conditionals as
      subjects from developed nations. Taken together, these findings support the
      hypotheses that social exchange algorithms are species-typical and that their
      evolutionarily stable strategy (ESS)-relevant subroutines are developmentally
      buffered against cultural variation.

PMID- 12177410
TI  - Gene expression during the priming phase of liver regeneration after partial
      hepatectomy in mice.
AB  - Understanding the gene-expression patterns during liver regeneration may help to
      reveal how regenerative processes are initiated and controlled as well as shed
      new light onto processes that lead to liver disease. Using high-density
      oligonucleotide arrays, we have examined the gene-expression program in the
      livers of mice after partial hepatectomy. A time course was constructed for gene
      expression between 0 and 4 h after partial hepatectomy, corresponding to the
      priming phase of liver regeneration. The genomic program for liver regeneration
      involves transcription-factor generation, stress and inflammatory responses,
      cytoskeletal and extracellular matrix modification, and regulation of cell-cycle
      entry. The genome-wide changes that are observed provide a detailed and
      comprehensive map of the initial priming stage of liver regeneration.

PMID- 12177412
TI  - Hybrid Tamarix widespread in U.S. invasion and undetected in native Asian range.
AB  - Biological invasions are drastically altering natural habitats and threatening
      biodiversity on both local and global levels. In one of the United States' worst
      invasions, Eurasian Tamarix plant species have spread rapidly to dominate over
      600,000 riparian and wetland hectares. The largest Tamarix invasion consists of
      Tamarix chinensis and Tamarix ramosissima, two morphologically similar species.
      To clarify the identity, origins, and population structuring of this invasion, we
      analyzed DNA sequence data from an intron of a nuclear gene, phosphoenolpyruvate
      carboxylase (PepC). This intron proved to be highly variable at the population
      level, and the 269 native and invasive specimens yielded 58 haplotypes, from
      which we constructed a gene genealogy. Only four of these haplotypes were common
      to both the U.S. and Eurasia. Surprisingly, we found that the most common plant
      in this U.S. invasion is a hybrid combination of two species-specific genotypes
      that were geographically isolated in their native Eurasian range. Less extensive
      hybrids exist in the invasion, involving combinations of T. ramosissima and T.
      chinensis with Tamarix parviflora and Tamarix gallica. The presence of
      potentially novel hybrids in the U.S. illustrates how importation of exotics can
      alter population structures of species and contribute to invasions.

PMID- 12177411
TI  - Loss of stearoyl-CoA desaturase-1 function protects mice against adiposity.
AB  - Stearoyl-CoA desaturase (SCD) is a central lipogenic enzyme catalyzing the
      synthesis of monounsaturated fatty acids, mainly oleate (C18:1) and palmitoleate
      (C16:1), which are components of membrane phospholipids, triglycerides, wax
      esters, and cholesterol esters. Several SCD isoforms (SCD1-3) exist in the mouse.
      Here we show that mice with a targeted disruption of the SCD1 isoform have
      reduced body adiposity, increased insulin sensitivity, and are resistant to diet
      induced weight gain. The protection from obesity involves increased energy
      expenditure and increased oxygen consumption. Compared with the wild-type mice
      the SCD1-/- mice have increased levels of plasma ketone bodies but reduced levels
      of plasma insulin and leptin. In the SCD1-/- mice, the expression of several
      genes of lipid oxidation are up-regulated, whereas lipid synthesis genes are down
      regulated. These observations suggest that a consequence of SCD1 deficiency is an
      activation of lipid oxidation in addition to reduced triglyceride synthesis and
      storage.

PMID- 12177413
TI  - Mismatch-targeted transposition of Mu: a new strategy to map genetic
      polymorphism.
AB  - Phage Mu DNA transposes to duplex target DNA sites with limited sequence
      specificity. Here we demonstrate that Mu transposition exhibits a strong target
      site preference for all single-nucleotide mismatches. This finding has
      implications for the mechanism of transposition and provides a powerful tool for
      genomic research. A single mismatch could be detected as a preferred target of Mu
      transposition in the presence of 300,000-fold excess of nonmismatched sites. We
      demonstrate the detection of both heterozygous and homozygous mutations in the
      cystic fibrosis transmembrane conductance regulator gene and single nucleotide
      polymorphism in HLA region by Mu transposition mismatch analysis procedure.

PMID- 12177414
TI  - Focusing of nitric oxide mediated nitrosation and oxidative nitrosylation as a
      consequence of reaction with superoxide.
AB  - The impact of nitric oxide (NO) synthesis on different biological cascades can
      rapidly change dependent on the rate of NO formation and composition of the
      surrounding milieu. With this perspective, we used diaminonaphthalene (DAN) and
      diaminofluorescein (DAF) to examine the nitrosative chemistry derived from NO and
      superoxide (O2-) simultaneously generated at nanomolar to low micromolar per
      minute rates by spermine/NO decomposition and xanthine oxidase-catalyzed
      oxidation of hypoxanthine, respectively. Fluorescent triazole product formation
      from DAN and DAF increased as the ratio of O2- to NO approached equimolar, then
      decreased precipitously as O2- exceeded NO. This pattern was also evident in DAF
      loaded MCF-7 carcinoma cells and when stimulated macrophages were used as the NO
      source. Cyclic voltammetry analysis and inhibition studies by using the N2O3
      scavenger azide indicated that DAN- and DAF-triazole could be derived from both
      oxidative nitrosylation (e.g., DAF radical + NO) and nitrosation (NO+ addition).
      The latter mechanism predominated with higher rates of NO formation relative to
      O2-. The effects of oxymyoglobin, superoxide dismutase, and carbon dioxide were
      examined as potential modulators of reactant availability for the O2- + NO
      pathway in vivo. The findings suggest that the outcome of NO biosynthesis in a
      scavenger milieu can be focused by O2- toward formation of NO adducts on
      nucleophilic residues (e.g., amines, thiols, hydroxyl) through convergent
      mechanisms involving the intermediacy of nitrogen dioxide. These modifications
      may be favored in microenvironments where the rate of O2- production is
      temporally and spatially contemporaneous with nitric oxide synthase activity, but
      not in excess of NO generation.

PMID- 12177416
TI  - Extinction rates under nonrandom patterns of habitat loss.
AB  - Most models that examine the effects of habitat conversion on species extinctions
      assume that habitat conversion occurs at random. This assumption allows
      predictions about extinction rates based on the species-area relationship. We
      show that the spatially aggregated nature of habitat conversion introduces a
      significant bias that may lead species-loss rates to exceed those predicted by
      species-area curves. Correlations between human activity and major compositional
      gradients, or species richness, also alter predicted species extinction rates. We
      illustrate the consequences of nonrandom patterns of habitat conversion by using
      a data set that combines the distribution of native vascular plants with human
      activity patterns in California.

PMID- 12177415
TI  - MHC heterozygosity confers a selective advantage against multiple-strain
      infections.
AB  - Genetic heterozygosity is thought to enhance resistance of hosts to infectious
      diseases, but few tests of this idea exist. In particular, heterozygosity at the
      MHC, the highly polymorphic loci that control immunological recognition of
      pathogens, is suspected to confer a selective advantage by enhancing resistance
      to infectious diseases (the "heterozygote advantage" hypothesis). To test this
      hypothesis, we released mice into large population enclosures and challenged them
      with multiple strains of Salmonella and one of Listeria. We found that during
      Salmonella infections with three avirulent strains, MHC heterozygotes had greater
      survival and weight than homozygotes (unlike sham controls), and they were more
      likely to clear chronic Salmonella infection than homozygotes. In laboratory
      experiments, we found that MHC heterozygosity enhanced the clearance of multiple
      strain Salmonella infections. Yet, contrary to what is widely assumed, the
      benefits of heterozygosity were due to resistance being dominant rather than
      overdominant, i.e., heterozygotes were more resistant than the average of
      parental homozygotes, but they were not more resistant than both. The fact that
      MHC heterozygotes were more resistant to infection and had higher fitness than
      homozygotes provides a functional explanation for MHC-disassortative mating
      preferences.

PMID- 12177418
TI  - Inhibition of calcineurin-NFAT hypertrophy signaling by cGMP-dependent protein
      kinase type I in cardiac myocytes.
AB  - Recent investigation has focused on identifying signaling pathways that inhibit
      cardiac hypertrophy, a major risk factor for cardiovascular morbidity and
      mortality. In this context, nitric oxide (NO), signaling via cGMP and cGMP
      dependent protein kinase type I (PKG I), has been recognized as a negative
      regulator of cardiac myocyte (CM) hypertrophy. However, the underlying mechanisms
      are poorly understood. Here, we show that PKG I inhibits CM hypertrophy by
      targeting the calcineurin-NFAT signaling pathway. Calcineurin, a Ca2+-dependent
      phosphatase, promotes hypertrophy in part by activating NFAT transcription
      factors which induce expression of hypertrophic genes, including brain
      natriuretic peptide (BNP). Activation of PKG I by NO/cGMP in CM suppressed NFAT
      transcriptional activity, BNP induction, and cell enlargement in response to
      alpha(1)-adrenoreceptor stimulation but not in response to adenoviral expression
      of a Ca2+-independent, constitutively active calcineurin mutant, thus
      demonstrating NO-cGMP-PKG I inhibition of calcineurin-NFAT signaling upstream of
      calcineurin. PKG I suppressed single L-type Ca2+-channel open probability,
      [Ca2+]i transient amplitude, and, most importantly, L-type Ca2+-channel current
      induced NFAT activation, indicating that PKG I targets Ca2+-dependent steps
      upstream of calcineurin. Adenoviral expression of PKG I enhanced NO/cGMP
      inhibitory effects upstream of calcineurin, confirming that PKG I mediates
      NO/cGMP inhibition of calcineurin-NFAT signaling. In CM overexpressing PKG I,
      NO/cGMP also suppressed BNP induction and cell enlargement but not NFAT
      activation elicited by constitutively active calcineurin, which is consistent
      with additional, NFAT-independent inhibitory effect(s) of PKG I downstream of
      calcineurin. Inhibition of calcineurin-NFAT signaling by PKG I provides a
      framework for understanding how NO inhibits cardiac myocyte hypertrophy.

PMID- 12177417
TI  - The reduction potential of nitric oxide (NO) and its importance to NO
      biochemistry.
AB  - A potential of about -0.8 (+/-0.2) V (at 1 M versus normal hydrogen electrode)
      for the reduction of nitric oxide (NO) to its one-electron reduced species,
      nitroxyl anion (3NO-) has been determined by a combination of quantum mechanical
      calculations, cyclic voltammetry measurements, and chemical reduction
      experiments. This value is in accord with some, but not the most commonly
      accepted, previous electrochemical measurements involving NO. Reduction of NO to
      1NO- is highly unfavorable, with a predicted reduction potential of about -1.7
      (+/-0.2) V at 1 M versus normal hydrogen electrode. These results represent a
      substantial revision of the derived and widely cited values of +0.39 V and -0.35
      V for the NO/3NO- and NO/1NO- couples, respectively, and provide support for
      previous measurements obtained by electrochemical and photoelectrochemical means.
      With such highly negative reduction potentials, NO is inert to reduction compared
      with physiological events that reduce molecular oxygen to superoxide. From these
      reduction potentials, the pKa of 3NO- has been reevaluated as 11.6 (+/-3.4).
      Thus, nitroxyl exists almost exclusively in its protonated form, HNO, under
      physiological conditions. The singlet state of nitroxyl anion, 1NO-, is
      physiologically inaccessible. The significance of these potentials to
      physiological and pathophysiological processes involving NO and O2 under
      reductive conditions is discussed.

PMID- 12177419
TI  - Designability of alpha-helical proteins.
AB  - A typical protein structure is a compact packing of connected alpha-helices
      and/or beta-strands. We have developed a method for generating the ensemble of
      compact structures a given set of helices and strands can form. The method is
      tested on structures composed of four alpha-helices connected by short turns. All
      such natural four-helix bundles that are connected by short turns seen in nature
      are reproduced to closer than 3.6 A per residue within the ensemble. Because
      structures with no natural counterpart may be targets for ab initio structure
      design, the designability of each structure in the ensemble-defined as the number
      of sequences with that structure as their lowest-energy state-is evaluated using
      a hydrophobic energy. For the case of four alpha-helices, a small set of highly
      designable structures emerges, most of which have an analog among the known four
      helix fold families; however, several packings and topologies with no analogs in
      protein database are identified.

PMID- 12177420
TI  - Caspase 3 activity is required for skeletal muscle differentiation.
AB  - The cellular alterations associated with skeletal muscle differentiation share a
      high degree of similarity with key phenotypic changes usually ascribed to
      apoptosis. For example, actin fiber disassembly/reorganization is a conserved
      feature of both apoptosis and differentiating myoblasts and the conserved muscle
      contractile protein, myosin light chain kinase, is required for the apoptotic
      feature of membrane blebbing. As such, these observations suggest that the
      induction of differentiation and apoptosis in the myogenic lineage may use
      overlapping cellular mechanisms. Here, we report that skeletal muscle
      differentiation depends on the activity of the key apoptotic protease, caspase 3.
      Peptide inhibition of caspase 3 activity or homologous deletion of caspase 3
      leads to dramatic reduction in both myotube/myofiber formation and expression of
      muscle-specific proteins. Subsequently, we have identified Mammalian Sterile
      Twenty-like kinase as a crucial caspase 3 effector in this cellular process.
      Mammalian Sterile Twenty-like kinase is cleavage-activated by caspase 3, and
      restoration of this truncated kinase in caspase 3 null myoblasts restores the
      differentiation phenotype. Taken together, these results confirm a unique and
      unanticipated role for a caspase 3-mediated signal cascade in the promotion of
      myogenesis.

PMID- 12177421
TI  - Identification of G protein-coupled receptors for Drosophila PRXamide peptides,
      CCAP, corazonin, and AKH supports a theory of ligand-receptor coevolution.
AB  - G-protein coupled receptors (GPCRs) are ancient, ubiquitous sensors vital to
      environmental and physiological signaling throughout organismal life. With the
      publication of the Drosophila genome, numerous "orphan" GPCRs have become
      available for functional analysis. Here we characterize two groups of GPCRs
      predicted as receptors for peptides with a C-terminal amino acid sequence motif
      consisting of -PRXamide (PRXa). Assuming ligand-receptor coevolution, two
      alternative hypotheses were constructed and tested. The insect PRXa peptides are
      evolutionarily related to the vertebrate peptide neuromedin U (NMU), or are
      related to arginine vasopressin (AVP), both of which have PRXa motifs. Seven
      Drosophila GPCRs related to receptors for NMU and AVP were cloned and expressed
      in Xenopus oocytes for functional analysis. Four Drosophila GPCRs in the NMU
      group (CG14575 [corrected], CG8795, CG9918, CG8784) are activated by insect PRXa
      pyrokinins, (-FXPRXamide), Cap2b-like peptides (-FPRXamide), or ecdysis
      triggering hormones (-PRXamide). Three Drosophila GPCRs in the vasopressin
      receptor group respond to crustacean cardioactive peptide (CCAP), corazonin, or
      adipokinetic hormone (AKH), none of which are PRXa peptides. These findings
      support a theory of coevolution for NMU and Drosophila PRXa peptides and their
      respective receptors.

PMID- 12177422
TI  - Creating nanocavities of tunable sizes: hollow helices.
AB  - A general strategy for creating nanocavities with tunable sizes based on the
      folding of unnatural oligomers is presented. The backbones of these oligomers are
      rigidified by localized, three-center intramolecular hydrogen bonds, which lead
      to well-defined hollow helical conformations. Changing the curvature of the
      oligomer backbone leads to the adjustment of the interior cavity size. Helices
      with interior cavities of 10 A to >30 A across, the largest thus far formed by
      the folding of unnatural foldamers, are generated. Cavities of these sizes are
      usually seen at the tertiary and quaternary structural levels of proteins. The
      ability to tune molecular dimensions without altering the underlying topology is
      seen in few natural and unnatural foldamer systems.

PMID- 12177423
TI  - Conservation of a portion of the S. cerevisiae Ure2p prion domain that interacts
      with the full-length protein.
AB  - The [URE3] prion of Saccharomyces cerevisiae is a self-propagating inactive
      amyloid form of the Ure2 protein. Ure2p residues 1-65 constitute the prion
      domain, and the remaining C-terminal portion regulates nitrogen catabolism. We
      have examined the URE2 genes of wild-type isolates of S. cerevisiae and those of
      several pathogenic yeasts and a filamentous fungus. We find that the normal
      function of the S. cerevisiae Ure2p in nitrogen regulation is fully complemented
      by the Ure2p of Candida albicans, Candida glabrata, Candida kefyr, Candida
      maltosa, Saccharomyces bayanus, and Saccharomyces paradoxus, all of which have
      high homology in the C-terminal nitrogen regulation domain. However, there is
      considerable divergence of their N-terminal domains from that of Ure2p of S.
      cerevisiae. [URE3(Sc)] showed efficient transmission into S. cerevisiae ure2Delta
      cells if expressing a Ure2p of species within Saccharomyces. However, [URE3(Sc)]
      did not seed self-propagating inactivation of the Ure2p's from the other yeasts.
      When overexpressed as a fusion with green fluorescent protein, residues 5-47 of
      the S. cerevisiae prion domain are necessary for curing the [URE3] prion.
      Residues 11-39 are necessary for an inactivating interaction with the full-length
      Ure2p. A nearly identical region is highly conserved among many of the yeasts
      examined in this study, despite the wide divergence of sequences found in other
      parts of the N-terminal domains.

PMID- 12177424
TI  - Reconsidering the null hypothesis: Is maternal rank associated with birth sex
      ratios in primate groups?
AB  - Trivers and Willard hypothesized that vertebrates adaptively vary the sex ratio
      of their offspring in response to the mother's physical condition [Trivers, R. L.
      & Willard, D. (1973) Science 179, 90-92]. This hypothesis has produced
      considerable debate within evolutionary biology. Here we use meta-analysis
      techniques to evaluate claims that nonhuman primate females facultatively adjust
      the sex ratio of their progeny in relation to their own dominance rank in a
      uniform way. The magnitude of the difference in birth sex ratios of high- and low
      ranking females declines as sample sizes increase, and the mean difference in
      birth sex ratios of high- and low-ranking females is zero. These results suggest
      that the observed effects could be the product of stochastic variation in small
      samples. These findings indicate that presently we cannot reject the null
      hypothesis that maternal dominance rank is unrelated to birth sex ratios.

PMID- 12177425
TI  - Hydration at the surface of the protein Monellin: dynamics with femtosecond
      resolution.
AB  - We have studied the femtosecond hydration dynamics of Monellin, a protein with a
      single tryptophan residue at its surface. Tryptophan was selectively used as a
      probe of the dynamics, and through monitoring of its fluorescence Stokes shift
      with time we obtained the hydration correlation function, which decays due to
      rotational and translational motions of water at the protein surface and in bulk.
      The decay exhibits a "bimodal" behavior with time constants of 1.3 and 16 ps,
      mirroring relaxation of the free/quasifree water molecules and surface-bound
      water layer (minimum binding energy of 1-2 kcal/mol). The observed slow decay of
      16 ps for tryptophan in the native protein differs by more than an order of
      magnitude from that of bulk water because of the dynamical exchange in the layer.
      To examine the effect of unfolding, we also studied hydration dynamics when
      Monellin was denatured in a 6 M guanidine hydrochloride solution and obtained a
      totally different behavior: 3.5 and 56 ps. Comparing with the results of
      experiments on free tryptophan in the same concentration of the denaturing
      solution, we conclude that the fast component of 3.5 ps comes from bulk-type
      solvation in the 6 M guanidine hydrochloride. However, the absence of the 16-ps
      decay and appearance of the 56-ps component reflects a more "rigid solvation,"
      which is likely to involve the motions of the protein backbone in the random
      coiled state. With the help of polymer theory, this time scale is reproduced in
      agreement with experimental observations.

PMID- 12177426
TI  - The gene expression fingerprint of human heart failure.
AB  - Multiple pathways are responsible for transducing mechanical and hormonal stimuli
      into changes in gene expression during heart failure. In this study our goals
      were (i) to develop a sound statistical method to establish a comprehensive
      cutoff point for identification of differentially expressed genes, (ii) to
      identify a gene expression fingerprint for heart failure, (iii) to attempt to
      distinguish different etiologies of heart failure by their gene expression
      fingerprint, and (iv) to identify gene clusters that show coordinated up- or down
      regulation in human heart failure. We used oligonucleotide microarrays to profile
      seven nonfailing (NF) and eight failing (F) human hearts with a diagnosis of end
      stage dilated cardiomyopathy. Biological and experimental variability of the
      hybridization data were analyzed, and then a statistical analysis procedure was
      developed, including Student's t test after log-transformation and Wilcoxon Mann
      Whitney test. A comprehensive cutoff point composed of fold change, average
      difference, and absolute call was then established and validated by TaqMan PCR.
      Of 6,606 genes on the GeneChip, 103 genes in 10 functional groups were
      differentially expressed between F and NF hearts. A dendrogram identified a gene
      expression fingerprint of F and NF hearts and also distinguished two F hearts
      with distinct etiologies (familial and alcoholic cardiomyopathy, respectively)
      with different expression patterns. K means clustering also revealed two
      potentially novel pathways associated with up-regulation of atrial natriuretic
      factor and brain natriuretic peptide and with increased expression of
      extracellular matrix proteins. Gene expression fingerprints may be useful
      indicators of heart failure etiologies.

PMID- 12177428
TI  - Wiskott-Aldrich syndrome protein is required for NK cell cytotoxicity and
      colocalizes with actin to NK cell-activating immunologic synapses.
AB  - The Wiskott-Aldrich syndrome (WAS) is a primary immunodeficiency disorder caused
      by a mutation in WAS protein (WASp) that results in defective actin
      polymerization. Although the function of many hematopoietic cells requires WASp,
      the specific expression and function of this molecule in natural killer (NK)
      cells is unknown. Here, we report that WAS patients have increased percentages of
      peripheral blood NK cells and that fresh enriched NK cells from two patients with
      a WASp mutation have defective cytolytic function. In normal NK cells, WASp was
      expressed and localized to the activating immunologic synapse (IS) with
      filamentous actin (F-actin). Perforin also localized to the NK cell-activating IS
      but at a lesser frequency than F-actin and WASp. The accumulation of F-actin and
      WASp at the activating IS was decreased significantly in NK cells that had been
      treated with the inhibitor of actin polymerization, cytochalasin D. NK cells from
      WAS patients lacked expression of WASp and accumulated F-actin at the activating
      IS infrequently. Thus, WASp has an important function in NK cells. In patients
      with WASp mutations, the resulting NK cell defects are likely to contribute to
      their disease.

PMID- 12177427
TI  - Molecular and biochemical characterization of two P450 enzymes in the
      ecdysteroidogenic pathway of Drosophila melanogaster.
AB  - Five different enzymatic activities, catalyzed by both microsomal and
      mitochondrial cytochrome P450 monooxygenases (CYPs), are strongly implicated in
      the biosynthesis of ecdysone (E) from cholesterol. However, none of these enzymes
      have been characterized completely. The present data show that the wild-type
      genes of two members of the Halloween family of embryonic lethals, disembodied
      (dib) and shadow (sad), code for mitochondrial cytochromes P450 that mediate the
      last two hydroxylation reactions in the ecdysteroidogenic pathway in Drosophila,
      namely the C22- and C2-hydroxylases. When sad (CYP315A1) is transfected into
      Drosophila S2 cells, the cells metabolize 2-deoxyecdysone (2dE) to E and the
      [3H]ketotriol (2,22-dideoxyecdysone) to 22-deoxyecdysone. In contrast, dib
      (CYP302A1) is responsible for the conversion of the [3H]ketotriol to [3H]2dE.
      When cells are transfected with both dib and sad, they metabolize the
      [3H]ketotriol to [3H]E in high yield. The expression of sad and dib is
      concentrated within the individual segments of the developing epidermis when
      there is a surge of ecdysteroid midway through embryogenesis. This result occurs
      before the ring gland has developed and suggests that the embryonic epidermis is
      a site of ecdysteroid biosynthesis. This pattern then diminishes, and, during
      late embryogenesis, expression of both genes is concentrated in the prothoracic
      gland cells of the developing ring gland. Expression of dib and sad continues to
      be localized in this endocrine compartment during larval development, being
      maximal in both the late second and third instar larvae, about the time of the
      premolt peaks in the ecdysteroid titer.

PMID- 12177429
TI  - Toward predicting protein topology: an approach to identifying beta hairpins.
AB  - Although secondary structure prediction methods have recently improved, progress
      from secondary to tertiary structure prediction has been limited. A promising but
      largely unexplored route to this goal is to predict structure motifs from
      secondary structure knowledge. Here we present a novel method for the recognition
      of beta hairpins that combines secondary structure predictions and threading
      methods by using a database search and a neural network approach. The method
      successfully predicts 48 and 77%, respectively, of all of hairpin and nonhairpin
      beta-coil-beta motifs in a protein database. We find that the main contributors
      to motif recognition are predicted accessibility and turn propensities.

PMID- 12177430
TI  - Biodiversity, population regulation, and the stability of coral-reef fish
      communities.
AB  - Unprecedented population declines and extinctions because of human activities,
      combined with a growing recognition that such losses affect the stability of
      ecosystems, underscore the need to better understand how populations persist
      naturally. We provide field experimental evidence that high biodiversity-in
      particular, the combined effects of predators and competitors-acts in a way that
      regulates the size of local fish populations within their coral-reef community.
      These results indicate that complex interactions among multiple species are
      necessary for the stability of a highly diverse community, and so forewarn that
      overexploiting such species may have cascading negative consequences for the
      entire system.

PMID- 12177431
TI  - Global analysis of the Deinococcus radiodurans proteome by using accurate mass
      tags.
AB  - Understanding biological systems and the roles of their constituents is
      facilitated by the ability to make quantitative, sensitive, and comprehensive
      measurements of how their proteome changes, e.g., in response to environmental
      perturbations. To this end, we have developed a high-throughput methodology to
      characterize an organism's dynamic proteome based on the combination of global
      enzymatic digestion, high-resolution liquid chromatographic separations, and
      analysis by Fourier transform ion cyclotron resonance mass spectrometry. The
      peptides produced serve as accurate mass tags for the proteins and have been used
      to identify with high confidence >61% of the predicted proteome for the ionizing
      radiation-resistant bacterium Deinococcus radiodurans. This fraction represents
      the broadest proteome coverage for any organism to date and includes 715 proteins
      previously annotated as either hypothetical or conserved hypothetical.

PMID- 12177432
TI  - Cosolvent-induced transformation of a death domain tertiary structure.
AB  - The death domain (DD) of the protein kinase Pelle adopts a six-helix bundle fold
      in the crystal structure of the complex with its dimerization partner, Tube-DD.
      However, in crystals obtained from a solution of 45% 2-methyl-2,4-pentanediol
      (MPD), the C-terminal half of Pelle-DD folds into a single helix, and the N
      terminal half of the molecule is disordered. The helical segment forms an
      antiparallel dimer with the corresponding helix of a symmetry-related molecule,
      and together they form extensive lattice interactions similar in number,
      composition, and buried surface to those in the six-helix bundle of the native
      fold. Secondary structure analysis by heteronuclear nuclear magnetic resonance
      spectroscopy (NMR) demonstrates that Pelle-DD adopts a six-helix bundle fold in
      aqueous solution. The fold is perturbed by MPD, with the largest chemical shift
      changes in one helix and two loop regions that encompass the Tube-DD binding
      site. Pelle-DD is stable to urea denaturation with a folding free energy of 7.9
      kcal/mol at 25 degrees C but is destabilized, with loss of urea binding sites, in
      the presence of MPD. The data are consistent with a cosolvent denaturation model
      in which MPD denatures the N terminus of Pelle-DD but induces the C terminus to
      form a more compact structure and aggregate. A similar perturbation in vivo might
      occur at the plasma membrane and could have consequences for Pelle-mediated
      regulation. Generally, crystallographers should be aware that high concentrations
      of MPD or related cosolvents can alter the tertiary structure of susceptible
      proteins.

PMID- 12177433
TI  - Two distinct modes of RecA action are required for DNA polymerase V-catalyzed
      translesion synthesis.
AB  - SOS mutagenesis in Escherichia coli requires DNA polymerase V (pol V) and RecA
      protein to copy damaged DNA templates. Here we show that two distinct biochemical
      modes for RecA protein are necessary for pol V-catalyzed translesion synthesis.
      One RecA mode is characterized by a strong stimulation in nucleotide
      incorporation either directly opposite a lesion or at undamaged template sites,
      but by the absence of lesion bypass. A separate RecA mode is necessary for
      translesion synthesis. The RecA1730 mutant protein, which was identified on the
      basis of its inability to promote pol V (UmuD'(2)C)-dependent UV-mutagenesis,
      appears proficient for the first mode of RecA action but is deficient in the
      second mode. Data are presented suggesting that the two RecA modes are
      "nonfilamentous". That is, contrary to current models for SOS mutagenesis,
      formation of a RecA nucleoprotein filament may not be required for copying
      damaged DNA templates. Instead, SOS mutagenesis occurs when pol V interacts with
      two RecA molecules, first at a 3' primer end, upstream of a template lesion,
      where RecA mode 1 stimulates pol V activity, and subsequently at a site
      immediately downstream of the lesion, where RecA mode 2 cocatalyzes lesion
      bypass. We posit that in vivo assembly of a RecA nucleoprotein filament may be
      required principally to target pol V to a site of DNA damage and to stabilize the
      pol V-RecA interaction at the lesion. However, it is only a RecA molecule located
      at the 3' filament tip, proximal to a damaged template base, that is directly
      responsible for translesion synthesis.

PMID- 12177434
TI  - Potent neutralization of botulinum neurotoxin by recombinant oligoclonal
      antibody.
AB  - The botulinum neurotoxins (BoNTs) cause the paralytic human disease botulism and
      are one of the highest-risk threat agents for bioterrorism. To generate a
      pharmaceutical to prevent or treat botulism, monoclonal antibodies (mAbs) were
      generated by phage display and evaluated for neutralization of BoNT serotype A
      (BoNT/A) in vivo. Although no single mAb significantly neutralized toxin, a
      combination of three mAbs (oligoclonal Ab) neutralized 450,000 50% lethal doses
      of BoNT/A, a potency 90 times greater than human hyperimmune globulin. The
      potency of oligoclonal Ab was primarily due to a large increase in functional Ab
      binding affinity. The results indicate that the potency of the polyclonal humoral
      immune response can be deconvoluted to a few mAbs binding nonoverlapping
      epitopes, providing a route to drugs for preventing and treating botulism and
      diseases caused by other pathogens and biologic threat agents.

PMID- 12177435
TI  - Genealogical evidence for epidemics of selfish genes.
AB  - Some genetic elements spread infectiously in populations by increasing their rate
      of genetic transmission at the expense of other genes in the genome. These so
      called selfish genetic elements comprise a substantial portion of eukaryotic
      genomes and have long been viewed as a potent evolutionary force. Despite this
      view, little is known about the evolutionary history of selfish genetic elements
      in natural populations, or their genetic effects on other portions of the genome.
      Here we use nuclear and chloroplast gene genealogies in two species of Silene to
      show the historical pattern of selection on a well known selfish genetic element,
      cytoplasmic male sterility. We provide evidence that evolution of cytoplasmic
      male sterility has been characterized by frequent turnovers of mutations in
      natural populations, thus supporting an epidemic model for the evolution of
      selfish genes, where new mutations repeatedly arise and rapidly sweep through
      populations.

PMID- 12177437
TI  - Imaging cells and extracellular matrix in vivo by using second-harmonic
      generation and two-photon excited fluorescence.
AB  - Multiphoton microscopy relies on nonlinear light-matter interactions to provide
      contrast and optical sectioning capability for high-resolution imaging. Most
      multiphoton microscopy studies in biological systems have relied on two-photon
      excited fluorescence (TPEF) to produce images. With increasing applications of
      multiphoton microscopy to thick-tissue "intravital" imaging, second-harmonic
      generation (SHG) from structural proteins has emerged as a potentially important
      new contrast mechanism. However, SHG is typically detected in transmission mode,
      thus limiting TPEF/SHG coregistration and its practical utility for in vivo thick
      tissue applications. In this study, we use a broad range of excitation
      wavelengths (730-880 nm) to demonstrate that TPEF/SHG coregistration can easily
      be achieved in unstained tissues by using a simple backscattering geometry. The
      combined TPEF/SHG technique was applied to imaging a three-dimensional
      organotypic tissue model (RAFT). The structural and molecular origin of the image
      forming signal from the various tissue constituents was determined by
      simultaneous spectroscopic measurements and confirming immunofluorescence
      staining. Our results show that at shorter excitation wavelengths (<800 nm), the
      signal emitted from the extracellular matrix (ECM) is a combination of SHG and
      TPEF from collagen, whereas at longer excitation wavelengths the ECM signal is
      exclusively due to SHG. Endogenous cellular signals are consistent with TPEF
      spectra of cofactors NAD(P)H and FAD at all excitation wavelengths. The reflected
      SHG intensity follows a quadratic dependence on the excitation power, decays
      exponentially with depth, and exhibits a spectral dependence in accordance with
      previous theoretical studies. The use of SHG and TPEF in combination provides
      complementary information that allows noninvasive, spatially localized in vivo
      characterization of cell-ECM interactions in unstained thick tissues.

PMID- 12177438
TI  - The evolution of multicomponent systems at high pressures: VI. The thermodynamic
      stability of the hydrogen-carbon system: the genesis of hydrocarbons and the
      origin of petroleum.
AB  - The spontaneous genesis of hydrocarbons that comprise natural petroleum have been
      analyzed by chemical thermodynamic-stability theory. The constraints imposed on
      chemical evolution by the second law of thermodynamics are briefly reviewed, and
      the effective prohibition of transformation, in the regime of temperatures and
      pressures characteristic of the near-surface crust of the Earth, of biological
      molecules into hydrocarbon molecules heavier than methane is recognized. For the
      theoretical analysis of this phenomenon, a general, first-principles equation of
      state has been developed by extending scaled particle theory and by using the
      technique of the factored partition function of the simplified perturbed hard
      chain theory. The chemical potentials and the respective thermodynamic Affinity
      have been calculated for typical components of the H-C system over a range of
      pressures between 1 and 100 kbar (1 kbar = 100 MPa) and at temperatures
      consistent with those of the depths of the Earth at such pressures. The
      theoretical analyses establish that the normal alkanes, the homologous
      hydrocarbon group of lowest chemical potential, evolve only at pressures greater
      than approximately 30 kbar, excepting only the lightest, methane. The pressure of
      30 kbar corresponds to depths of approximately 100 km. For experimental
      verification of the predictions of the theoretical analysis, a special high
      pressure apparatus has been designed that permits investigations at pressures to
      50 kbar and temperatures to 1,500 degrees C and also allows rapid cooling while
      maintaining high pressures. The high-pressure genesis of petroleum hydrocarbons
      has been demonstrated using only the reagents solid iron oxide, FeO, and marble,
      CaCO3, 99.9% pure and wet with triple-distilled water.

PMID- 12177436
TI  - Defects in caveolin-1 cause dilated cardiomyopathy and pulmonary hypertension in
      knockout mice.
AB  - Caveolins are important components of caveolae, which have been implicated in
      vesicular trafficking and signal transduction. To investigate the in vivo
      significance of Caveolins in mammals, we generated mice deficient in the caveolin
      1 (cav-1) gene and have shown that, in the absence of Cav-1, no caveolae
      structures were observed in several nonmuscle cell types. Although cav-1(-/-)
      mice are viable, histological examination and echocardiography identified a
      spectrum of characteristics of dilated cardiomyopathy in the left ventricular
      chamber of the cav-1-deficient hearts, including an enlarged ventricular chamber
      diameter, thin posterior wall, and decreased contractility. These animals also
      have marked right ventricular hypertrophy, suggesting a chronic increase in
      pulmonary artery pressure. Direct measurement of pulmonary artery pressure and
      histological analysis revealed that the cav-1(-/-) mice exhibit pulmonary
      hypertension, which may contribute to the right ventricle hypertrophy. In
      addition, the loss of Cav-1 leads to a dramatic increase in systemic NO levels.
      Our studies provided in vivo evidence that cav-1 is essential for the control of
      systemic NO levels and normal cardiopulmonary function.

PMID- 12177439
TI  - ClpAP and ClpXP degrade proteins with tags located in the interior of the primary
      sequence.
AB  - Clp/Hsp100 ATPases comprise a large family of ATP-dependent chaperones, some of
      which are regulatory components of two-component proteases. Substrate specificity
      resides in the Clp protein and the current thinking is that Clp proteins
      recognize motifs located near one or the other end of the substrate. We tested
      whether or not ClpA and ClpX can recognize tags when they are located in the
      interior of the primary sequence of the substrate. A protein with an NH2-terminal
      ClpA recognition tag, plasmid P1 RepA, was fused to the COOH terminus of green
      fluorescent protein (GFP). GFP is not recognized by ClpA or ClpX and is not
      degraded by ClpAP or ClpXP. We found that ClpA binds and unfolds the fusion
      protein and ClpAP degrades the protein. Both the GFP and RepA portions of the
      fusion protein are degraded. A protein with a COOH-terminal ClpX tag, MuA, was
      fused to the NH2 terminus of GFP. ClpXP degrades MuA-GFP, however, the rate is 10
      fold slower than that of GFP-MuA. The MuA portion but not the GFP portion of MuA
      GFP is degraded. Thus, a substrate with an internal ClpA recognition motif can be
      unfolded by ClpA and degraded by ClpAP. Similarly, although less efficiently,
      ClpXP degrades a substrate with an internal ClpX recognition motif. We also found
      that ClpA recognizes the NH2-terminal 15 aa RepA tag, when it is fused to the
      COOH terminus of GFP. Moreover, ClpA recognizes the RepA tag in either the
      authentic or inverse orientation.

PMID- 12177440
TI  - A phylogenetic analysis of myosin heavy chain type II sequences corroborates that
      Acoela and Nemertodermatida are basal bilaterians.
AB  - Bilateria are currently subdivided into three superclades: Deuterostomia,
      Ecdysozoa, and Lophotrochozoa. Within this new taxonomic frame, acoelomate
      Platyhelminthes, for a long time held to be basal bilaterians, are now considered
      spiralian lophotrochozoans. However, recent 18S rDNA [small subunit (SSU)]
      analyses have shown Platyhelminthes to be polyphyletic with two of its orders,
      the Acoela and the Nemertodermatida, as the earliest extant bilaterians. To
      corroborate such position and avoid the criticisms of saturation and long-branch
      effects thrown on the SSU molecule, we have searched for independent molecular
      data bearing good phylogenetic information at deep evolutionary nodes. Here we
      report a phylogenetic analysis of DNA sequences from the myosin heavy chain type
      II (myosin II) gene from a large set of metazoans, including acoels and
      nemertodermatids. Our study demonstrates, both for the myosin II data set alone
      and for a combined SSU + myosin II data set, that Platyhelminthes are
      polyphyletic and that acoels and nemertodermatids are the extant earliest
      bilaterians. Hence, the common bilaterian ancestor was not, as currently held,
      large and complex but small, simple, and likely with direct development. This
      scenario has far-reaching implications for understanding the evolution of major
      body plans and for perceptions of the Cambrian evolutionary explosion.

PMID- 12177441
TI  - Peptide linkage mapping of the Agrobacterium tumefaciens vir-encoded type IV
      secretion system reveals protein subassemblies.
AB  - Numerous bacterial pathogens use type IV secretion systems (T4SS) to deliver
      virulence factors directly to the cytoplasm of plant, animal, and human host
      cells. Here, evidence for interactions among components of the Agrobacterium
      tumefaciens vir-encoded T4SS is presented. The results derive from a high
      resolution yeast two-hybrid assay, in which a library of small peptide domains of
      T4SS components was screened for interactions. The use of small peptides
      overcomes problems associated with assaying for interactions involving membrane
      associated proteins. We established interactions between VirB11 (an inner
      membrane pore-forming protein), VirB9 (a periplasmic protein), and VirB7 (an
      outer membrane-associated lipoprotein and putative pilus component). We provide
      evidence for an interaction pathway, among conserved members of a T4SS, spanning
      the A. tumefaciens envelope and including a potential pore protein. In addition,
      we have determined interactions between VirB1 (a lytic transglycosylase likely
      involved in the local remodeling of the peptidoglycan) and primarily VirB8, but
      also VirB4, VirB10, and VirB11 (proteins likely to assemble the core structure of
      the T4SS). VirB4 interacts with VirB8, VirB10, and VirB11, also establishing a
      connection to the core components. The identification of these interactions
      suggests a model for assembly of the T4SS.

PMID- 12177442
TI  - Integral membrane proteins of the chloroplast envelope: identification and
      subcellular localization of new transporters.
AB  - A two-membrane system, or envelope, surrounds plastids. Because of the
      integration of chloroplast metabolism within the plant cell, the envelope is the
      site of many specific transport activities. However, only a few proteins involved
      in the processes of transport across the chloroplast envelope have been
      identified already at the molecular level. To discover new envelope transporters,
      we developed a subcellular proteomic approach, which is aimed to identify the
      most hydrophobic envelope proteins. This strategy combined the use of highly
      purified and characterized membrane fractions, extraction of the hydrophobic
      proteins with organic solvents, SDS/PAGE separation, and tandem mass spectrometry
      analysis. To process the large amount of MS/MS data, a blast-based program was
      developed for searching in protein, expressed sequence tag, and genomic plant
      databases. Among the 54 identified proteins, 27 were new envelope proteins, with
      most of them bearing multiple alpha-helical transmembrane regions and being very
      likely envelope transporters. The present proteomic study also allowed us to
      identify common features among the known and newly identified putative envelope
      inner membrane transporters. These features were used to mine the complete
      Arabidopsis genome and allowed us to establish a virtual plastid envelope
      integral protein database. Altogether, both proteomic and in silico approaches
      identified more than 50 candidates for the as yet previously uncharacterized
      plastid envelope transporters. The predictable function of some of these proteins
      opens up areas of investigation that may lead to a better understanding of the
      chloroplast metabolism. The present subcellular proteomic approach is amenable to
      the analysis of the hydrophobic core of other intracellular membrane systems.

PMID- 12177443
TI  - Detergent extraction identifies different VirB protein subassemblies of the type
      IV secretion machinery in the membranes of Agrobacterium tumefaciens.
AB  - The VirB/D4 type IV secretion system of Agrobacterium tumefaciens translocates
      virulence factors (VirE2, VirF, and the VirD2-T-DNA complex) to plant cells. The
      membrane-bound translocation machinery consists of 12 proteins (VirB1-11 and
      VirD4) required for substrate translocation. Protein-protein interactions in the
      membranes were analyzed after extraction with the mild detergent dodecyl-beta-d
      maltoside followed by separation under native conditions. Incubation of the
      membranes with increasing concentrations of the detergent differentially
      extracted virulence proteins. Separation of the solubilized proteins by blue
      native electrophoresis revealed cofractionation between two classes of protein
      complexes containing VirB7. The first class, consisting of major T-pilus
      component VirB2 and associated proteins VirB5 and VirB7, comigrated in the low
      molecular mass portion of the gel of about 100 kDa. The second class contains
      putative translocation complex core components VirB8, VirB9, and VirB10 in the
      high molecular mass portion of the gel larger than 232 kDa, as well as VirB7.
      Solubilized proteins were characterized further by gel filtration chromatography.
      This procedure separated T-pilus-associated proteins VirB2, VirB5, and VirB7 in
      the low molecular mass range from the other components of the translocation
      machinery and the substrates VirE2 and VirD2. Fractionation of VirB7-containing
      complexes (VirB7-VirB7 homodimers and VirB7-VirB9 heterodimers) suggested that
      they may link the T-pilus components to the core of the translocation machinery.
      Based on previously described VirB protein interactions and biochemical analysis
      of C58 wild type as well as of virB5 and virB6 deletion mutants, a model of T
      pilus assembly in A. tumefaciens is suggested.

PMID- 12177444
TI  - Interchain vs. intrachain energy transfer in acceptor-capped conjugated polymers.
AB  - The energy-transfer processes taking place in conjugated polymers are
      investigated by means of ultrafast spectroscopy and correlated quantum-chemical
      calculations applied to polyindenofluorenes end-capped with a perylene
      derivative. Comparison between the time-integrated luminescence and transient
      absorption spectra measured in solution and in films allows disentangling of the
      contributions arising from intrachain and from interchain energy-migration
      phenomena. Intrachain processes dominate in solution where photoexcitation of the
      polyindenofluorene units induces a rather slow energy transfer to the perylene
      end moieties. In films, close contacts between chains favors interchain transport
      of the excited singlet species (from the conjugated bridge of one chain to the
      perylene unit of a neighboring one); this process is characterized by a 1-order
      of-magnitude increase in transfer rate with respect to solution. This description
      is supported fully by the results of quantum-chemical calculations that go beyond
      the usual point-dipole model approximation and account for geometric relaxation
      phenomena in the excited state before energy migration. The calculations indicate
      a two-step mechanism for intrachain energy transfer with hopping along the
      conjugated chains as the rate-limiting step; the higher efficiency of the
      interchain transfer process is mainly due to larger electronic coupling matrix
      elements between closely lying chains.

PMID- 12177445
TI  - VEGF-Trap: a VEGF blocker with potent antitumor effects.
AB  - Vascular endothelial growth factor (VEGF) plays a critical role during normal
      embryonic angiogenesis and also in the pathological angiogenesis that occurs in a
      number of diseases, including cancer. Initial attempts to block VEGF by using a
      humanized monoclonal antibody are beginning to show promise in human cancer
      patients, underscoring the importance of optimizing VEGF blockade. Previous
      studies have found that one of the most effective ways to block the VEGF
      signaling pathway is to prevent VEGF from binding to its normal receptors by
      administering decoy-soluble receptors. The highest-affinity VEGF blocker
      described to date is a soluble decoy receptor created by fusing the first three
      Ig domains of VEGF receptor 1 to an Ig constant region; however, this fusion
      protein has very poor in vivo pharmacokinetic properties. By determining the
      requirements to maintain high affinity while extending in vivo half life, we were
      able to engineer a very potent high-affinity VEGF blocker that has markedly
      enhanced pharmacokinetic properties. This VEGF-Trap effectively suppresses tumor
      growth and vascularization in vivo, resulting in stunted and almost completely
      avascular tumors. VEGF-Trap-mediated blockade may be superior to that achieved by
      other agents, such as monoclonal antibodies targeted against the VEGF receptor.

PMID- 12177446
TI  - Potent VEGF blockade causes regression of coopted vessels in a model of
      neuroblastoma.
AB  - Vascular endothelial growth factor (VEGF) plays a key role in human tumor
      angiogenesis. We compared the effects of inhibitors of VEGF with different
      specificities in a xenograft model of neuroblastoma. Cultured human neuroblastoma
      NGP-GFP cells were implanted intrarenally in nude mice. Three anti-VEGF agents
      were tested: an anti-human VEGF(165) RNA-based fluoropyrimidine aptamer; a
      monoclonal anti-human VEGF antibody; and VEGF-Trap, a composite decoy receptor
      based on VEGFR-1 and VEGFR-2 fused to an Fc segment of IgG1. A wide range of
      efficacy was observed, with high-dose VEGF-Trap causing the greatest inhibition
      of tumor growth (81% compared with controls). We examined tumor angiogenesis and
      found that early in tumor formation, cooption of host vasculature occurs. We
      postulate that this coopted vasculature serves as a source of blood supply during
      the initial phase of tumor growth. Subsequently, control tumors undergo vigorous
      growth and remodeling of vascular networks, which results in disappearance of the
      coopted vessels. However, if VEGF function is blocked, cooption of host vessels
      may persist. Persistent cooption, therefore, may represent a novel mechanism by
      which neuroblastoma can partly evade antiangiogenic therapy and may explain why
      experimental neuroblastoma is less susceptible to VEGF blockade than a parallel
      model of Wilms tumor. However, more effective VEGF blockade, as achieved by high
      doses of VEGF-Trap, can lead to regression of coopted vascular structures. These
      results demonstrate that cooption of host vasculature is an early event in tumor
      formation, and that persistence of this effect is related to the degree of
      blockade of VEGF activity.

PMID- 12177447
TI  - Febrile temperatures induce cytoadherence of ring-stage Plasmodium falciparum
      infected erythrocytes.
AB  - In falciparum malaria, the malaria parasite induces changes at the infected red
      blood cell surface that lead to adherence to vascular endothelium and other red
      blood cells. As a result, the more mature stages of Plasmodium falciparum are
      sequestered in the microvasculature and cause vital organ dysfunction, whereas
      the ring stages circulate in the blood stream. Malaria is characterized by fever.
      We have studied the effect of febrile temperatures on the cytoadherence in vitro
      of P. falciparum-infected erythrocytes. Freshly obtained ring-stage-infected red
      blood cells from 10 patients with acute falciparum malaria did not adhere to the
      principle vascular adherence receptors CD36 or intercellular adhesion molecule-1
      (ICAM-1). However, after a brief period of heating to 40 degrees C, all ring
      infected red blood cells adhered to CD36, and some isolates adhered to ICAM-1,
      whereas controls incubated at 37 degrees C did not. Heating to 40 degrees C
      accelerated cytoadherence and doubled the maximum cytoadherence observed (P <
      0.01). Erythrocytes infected by ring-stages of the ICAM-1 binding clone A4var
      also did not cytoadhere at 37 degrees C, but after heating to febrile
      temperatures bound to both CD36 and ICAM-1. Adherence of red blood cells infected
      with trophozoites was also increased considerably by brief heating. The factor
      responsible for heat induced adherence was shown to be the parasite derived
      variant surface protein PfEMP-1. RNA analysis showed that levels of var mRNA did
      not differ between heated and unheated ring-stage parasites. Thus fever-induced
      adherence appeared to involve increased trafficking of PfEMP-1 to the erythrocyte
      membrane. Fever induced cytoadherence is likely to have important pathological
      consequences and may explain both clinical deterioration with fever in severe
      malaria and the effects of antipyretics on parasite clearance.

PMID- 12177448
TI  - Histone H3 variants specify modes of chromatin assembly.
AB  - Histone variants have been known for 30 years, but their functions and the
      mechanism of their deposition are still largely unknown. Drosophila has three
      versions of histone H3. H3 packages the bulk genome, H3.3 marks active chromatin
      and may be essential for gene regulation, and Cid is the characteristic
      structural component of centromeric chromatin. We have characterized the
      properties of these histones by using a Drosophila cell-line system that allows
      precise analysis of both DNA replication and histone deposition. The deposition
      of H3 is restricted to replicating DNA. In striking contrast, H3.3 and Cid
      deposit throughout the cell cycle. Deposition of H3.3 occurs without any
      corresponding DNA replication. To confirm that the deposition of Cid is also
      replication-independent (RI), we examined centromere replication in cultured
      cells and neuroblasts. We found that centromeres replicate out of phase with
      heterochromatin and display replication patterns that may limit H3 deposition.
      This confirms that both variants undergo RI deposition, but at different
      locations in the nucleus. How variant histones accomplish RI deposition is
      unknown, and raises basic questions about the stability of nucleosomes, the
      machinery that accomplishes nucleosome assembly, and the functional organization
      of the nucleus. The different in vivo properties of H3, H3.3, and Cid set the
      stage for identifying the mechanisms by which they are differentially targeted.
      Here we suggest that local effects of "open" chromatin and broader effects of
      nuclear organization help to guide the two different H3 variants to their target
      sites.

PMID- 12177449
TI  - Neural processing of emotional faces requires attention.
AB  - Attention gates the processing of stimuli relatively early in visual cortex. Yet,
      existing data suggest that emotional stimuli activate brain regions
      automatically, largely immune from attentional control. To resolve this puzzle,
      we used functional magnetic resonance imaging to first measure activation in
      regions that responded differentially to faces with emotional expressions
      (fearful and happy) compared with neutral faces. We then measured the modulation
      of these responses by attention, using a competing task with a high attentional
      load. Contrary to the prevailing view, all brain regions responding
      differentially to emotional faces, including the amygdala, did so only when
      sufficient attentional resources were available to process the faces. Thus, the
      processing of facial expression appears to be under top-down control.

PMID- 12177450
TI  - Newly generated neurons in the amygdala and adjoining cortex of adult primates.
AB  - The subventricular zone remains mitotically active throughout life in rodents.
      Studies with tritiated thymidine, which is incorporated into the DNA of mitotic
      cells, have revealed that the rodent subventricular zone produces neuroblasts
      that migrate toward the olfactory bulb along the rostral migratory stream. A
      similar migratory stream has been documented in monkeys by using the thymidine
      analogue BrdUrd. The same approach showed that neurogenesis occurred in the
      dentate gyrus of adult primates, including humans. In the present study,
      experiments combining injections of BrdUrd and the dye 1,1'-dioctadecyl-3,3,3',3'
      tetramethylindo-carbocyanine, with the immunostaining for molecular markers of
      neurogenesis (polysialylated neural cell adhesion molecule, beta-tubulin-III,
      collapsin response mediator protein-4, neuronal nuclear protein) in New World
      (Saimiri sciureus) and Old World (Macaca fascicularis) monkeys have revealed that
      new neurons are produced in the amygdala, piriform cortex, and adjoining inferior
      temporal cortex in adult primates. These newborn neurons expressed the
      antiapoptotic protein Bcl-2 and formed a more-or-less continuous pathway that
      extended from the tip of the temporal ventricular horn to the deep portion of the
      temporal lobe. The production of newborn neurons in the amygdala, piriform
      cortex, and inferior temporal cortex seems to parallel the continuing addition of
      neurons in the olfactory bulb. These two concomitant phenomena may ensure
      structural stability and functional plasticity to the primate olfactory system
      and temporal lobe.

PMID- 12177451
TI  - Adverse effects of acid rain on the distribution of the Wood Thrush Hylocichla
      mustelina in North America.
AB  - Research into population declines of North American bird species has mainly
      focused on the fragmentation of habitat on the breeding or wintering grounds
      [Robinson, S. K., Thompson, F. R., Donovan, T. M., Whitehead, D. R. & Faaborg, J.
      (1995) Science 267, 1987-1990]. In contrast, research into declines of European
      species has mainly focused on intensification of agriculture [Donald, P. F.,
      Green, R. E. & Heath, M. F. (2001) Proc. R. Soc. London Ser. B 268, 25-29] and
      the role played by the atmospheric deposition of pollutants, in particular, acid
      rain [Graveland, J. (1998) Environ. Rev. 6, 41-54]. However, despite widespread
      unexplained declines of bird populations in regions of heavy wet acid ion
      deposition [Sauer, J. R., Hines, J. E. & Fallon, J. (2001) The North American
      Breeding Bird Survey Results and Analysis 1966-2000 (Patuxent Wildlife Research
      Center, Laurel, MD)], no North American studies have presented evidence linking
      such widespread terrestrial bird declines to acid rain. To address the question
      of the role played by acid rain in population declines of eastern North American
      songbird species, we combine data from several sources. We use a multiple
      logistic regression model to test for adverse effects of acid rain on the Wood
      Thrush, while controlling for regional abundance, landscape-level habitat
      fragmentation, elevation, soil pH, and vegetation. We show a strong, highly
      significant, negative effect of acid rain on the predicted probability of
      breeding by this species, and interactions with elevation, low pH soils, and
      habitat fragmentation that worsen these negative effects. Our results suggest an
      important role for acid rain in recent declines of some birds breeding in the
      eastern United States, particularly in high elevation zones with low pH soils,
      and show the need to consider other large-scale influences, in addition to
      habitat fragmentation, when addressing bird population declines.

PMID- 12177452
TI  - Dissociable prefrontal brain systems for attention and emotion.
AB  - The prefrontal cortex has been implicated in a variety of attentional, executive,
      and mnemonic mental operations, yet its functional organization is still highly
      debated. The present study used functional MRI to determine whether attentional
      and emotional functions are segregated into dissociable prefrontal networks in
      the human brain. Subjects discriminated infrequent and irregularly presented
      attentional targets (circles) from frequent standards (squares) while novel
      distracting scenes, parametrically varied for emotional arousal, were
      intermittently presented. Targets differentially activated middle frontal gyrus,
      posterior parietal cortex, and posterior cingulate gyrus. Novel distracters
      activated inferior frontal gyrus, amygdala, and fusiform gyrus, with
      significantly stronger activation evoked by the emotional scenes. The anterior
      cingulate gyrus was the only brain region with equivalent responses to
      attentional and emotional stimuli. These results show that attentional and
      emotional functions are segregated into parallel dorsal and ventral streams that
      extend into prefrontal cortex and are integrated in the anterior cingulate. These
      findings may have implications for understanding the neural dynamics underlying
      emotional distractibility on attentional tasks in affective disorders.

PMID- 12177453
TI  - Enzymology below 200 K: the kinetics and thermodynamics of the photochemistry
      catalyzed by protochlorophyllide oxidoreductase.
AB  - The chlorophyll biosynthesis enzyme protochlorophyllide reductase (POR) catalyzes
      the light-dependent reduction of protochlorophyllide (Pchlide) into
      chlorophyllide in the presence of NADPH. As POR is light-dependent, catalysis can
      be initiated by illumination of the enzyme-substrate complex at low temperatures,
      making it an attractive model for studying aspects of biological proton and
      hydride transfers. The early stages in the photoreduction, involving Pchlide
      binding and an initial photochemical reaction, have been studied in vitro by
      using low-temperature fluorescence and absorbance measurements. Formation of the
      ternary POR-NADPH-Pchlide complex produces red shifts in the fluorescence and
      absorbance maxima of Pchlide, allowing the dissociation constant for Pchlide
      binding to be measured. We demonstrate that the product of an initial
      photochemical reaction, which can occur below 200 K, is a nonfluorescent
      intermediate with a broad absorbance band at 696 nm (A696) that is suggested to
      represent an ion radical complex. The temperature dependence of the rate of A696
      formation has allowed the activation energy for the photochemical step to be
      calculated and has shown that POR catalysis can proceed at much lower
      temperatures than previously thought. Calculations of differences in free energy
      between various reaction intermediates have been calculated; these, together with
      the quantum efficiency for Pchlide conversion, suggest a quantitative model for
      the thermodynamics of the light-driven step of Pchlide reduction.

PMID- 12177454
TI  - New technology may reveal mechanisms of radiation resistance in Deinococcus
      radiodurans.

PMID- 12177455
TI  - Double labeling of KNOTTED1 mRNA and protein reveals multiple potential sites of
      protein trafficking in the shoot apex.
AB  - Recent reports indicate that several plant mRNAs and proteins are able to traffic
      intercellularly through plasmodesmata. Localization studies can reveal
      differences between mRNA and protein localization that would be indicative of
      such a process. However, subtle differences could be missed when comparing
      localization in adjacent sections, especially in developmental studies where
      adjacent sections through immature apical regions may be one or more cells
      removed from each other. Therefore, we have developed a novel method for double
      localization of KNOTTED1 mRNA and protein in sections through the maize (Zea
      mays) shoot apex. The advantage of double labeling is revealed in our
      demonstration of novel potential sites of cell-to-cell trafficking of KNOTTED1
      protein in the shoot apical region. The technique should be applicable to any
      gene products where the appropriate probes are available and will, therefore,
      help to determine the extent of protein and/or mRNA trafficking in plants.

PMID- 12177456
TI  - Insect footsteps on leaves stimulate the accumulation of 4-aminobutyrate and can
      be visualized through increased chlorophyll fluorescence and superoxide
      production.

PMID- 12177457
TI  - Revisiting the metal-binding chemistry of nicotianamine and 2'-deoxymugineic
      acid. Implications for iron nutrition in strategy II plants.

PMID- 12177458
TI  - Beyond the Arabidopsis genome: opportunities for comparative genomics.

PMID- 12177459
TI  - Using genomic resources to guide research directions. The arabinogalactan protein
      gene family as a test case.
AB  - Arabinogalactan proteins (AGPs) are extracellular hydroxyproline-rich
      proteoglycans implicated in plant growth and development. The protein backbones
      of AGPs are rich in proline/hydroxyproline, serine, alanine, and threonine. Most
      family members have less than 40% similarity; therefore, finding family members
      using Basic Local Alignment Search Tool searches is difficult. As part of our
      systematic analysis of AGP function in Arabidopsis, we wanted to make sure that
      we had identified most of the members of the gene family. We used the biased
      amino acid composition of AGPs to identify AGPs and arabinogalactan (AG) peptides
      in the Arabidopsis genome. Different criteria were used to identify the fasciclin
      like AGPs. In total, we have identified 13 classical AGPs, 10 AG-peptides, three
      basic AGPs that include a short lysine-rich region, and 21 fasciclin-like AGPs.
      To streamline the analysis of genomic resources to assist in the planning of
      targeted experimental approaches, we have adopted a flow chart to maximize the
      information that can be obtained about each gene. One of the key steps is the
      reformatting of the Arabidopsis Functional Genomics Consortium microarray data.
      This customized software program makes it possible to view the ratio data for all
      Arabidopsis Functional Genomics Consortium experiments and as many genes as
      desired in a single spreadsheet. The results for reciprocal experiments are
      grouped to simplify analysis and candidate AGPs involved in development or biotic
      and abiotic stress responses are readily identified. The microarray data support
      the suggestion that different AGPs have different functions.

PMID- 12177460
TI  - ACTIN2 is essential for bulge site selection and tip growth during root hair
      development of Arabidopsis.
AB  - Root hairs develop as long extensions from root epidermal cells. After the
      formation of an initial bulge at the distal end of the epidermal cell, the root
      hair structure elongates by tip growth. Because root hairs are not surrounded by
      other cells, root hair formation provides an excellent system for studying the
      highly complex process of plant cell growth. Pharmacological experiments with
      actin filament-interfering drugs have provided evidence that the actin
      cytoskeleton is an important factor in the establishment of cell polarity and in
      the maintenance of the tip growth machinery at the apex of the growing root hair.
      However, there has been no genetic evidence to directly support this assumption.
      We have isolated an Arabidopsis mutant, deformed root hairs 1 (der1), that is
      impaired in root hair development. The DER1 locus was cloned by map-based cloning
      and encodes ACTIN2 (ACT2), a major actin of the vegetative tissue. The three der1
      alleles develop the mutant phenotype to different degrees and are all missense
      mutations, thus providing the means to study the effect of partially functional
      ACT2. The detailed characterization of the der1 phenotypes revealed that ACT2 is
      not only involved in root hair tip growth, but is also required for correct
      selection of the bulge site on the epidermal cell. Thus, the der1 mutants are
      useful tools to better understand the function of the actin cytoskeleton in the
      process of root hair formation.

PMID- 12177461
TI  - High-level and ubiquitous expression of the rice cytochrome c gene OsCc1 and its
      promoter activity in transgenic plants provides a useful promoter for
      transgenesis of monocots.
AB  - Expression patterns of a rice (Oryza sativa) cytochrome c gene OsCc1 and its
      promoter activity were characterized in transgenic rice plants. OsCc1 transcripts
      accumulate in most cell types, but to varying levels. Large amounts of OsCc1
      transcripts are found in the roots, calli, and suspension cells, but relatively
      lower in mature leaves, demonstrating its higher levels of expression in non
      photosynthetic tissues. Unlike the human cytochrome c gene, which is responsive
      to cAMP, OsCc1 expression is not enhanced in various rice tissues after dibutyryl
      cAMP treatments. OsCc1 promoter was linked to the sgfp gene and its activities in
      different tissues and cell types of transgenic rice plants were analyzed in
      comparison with the Act1 and RbcS promoters. OsCc1 promoter directs expression in
      virtually all organs of transgenic plants including roots, leaves, calli,
      embryos, and suspension cells, showing a particularly high activity in calli and
      roots. Activity of the OsCc1 promoter was 3-fold higher than Act1 in calli and
      roots and comparable with RbcS in leaves, representing a useful alternative to
      the maize (Zea mays) Ubi1 and the rice Act1 promoters for transgene expression in
      monocots.

PMID- 12177462
TI  - The expression of HAK-type K(+) transporters is regulated in response to salinity
      stress in common ice plant.
AB  - Four transcripts homologous to K(+) transporters of the HAK/KT/KUP family have
      been characterized from the common ice plant (Mesembryanthemum crystallinum). We
      report tissue-specific expression of McHAK1 and McHAK4 transcripts abundant in
      roots, leaves, and stems. McHAK2 was predominantly present in stems and McHAK3 in
      root tissues. By in situ hybridizations, the McHAKs showed signals in the leaf
      vascular bundles, mesophyll, and epidermal cells as well as in epidermal bladder
      cells. In mature roots, transcripts were mainly localized to the vasculature, and
      in differentiated root tips, the strongest signals were obtained from the
      epidermis. Expression of McHAK1, McHAK2, and McHAK4 complemented a yeast mutant
      defective in low- and high-affinity K(+) uptake. Growth of the yeast mutant was
      restored at low-millimolar K(+) concentrations and was inhibited by Rb(+) and
      Cs(+) but was not affected by Na(+). Transcript levels of McHAK1 and McHAK4
      increased by K(+) starvation and by salt stress of 400 mM NaCl in leaves and
      roots. Expression of McHAK2 and McHAK3 was stimulated in leaves and was
      transiently induced in roots in response to high salinity with prestress
      transcript levels restored in salt-adapted plants. We discuss possible roles for
      such transporters in ion homeostasis at high salinity.

PMID- 12177463
TI  - Expression analysis of a family of nsLTP genes tissue specifically expressed
      throughout the plant and during potato tuber life cycle.
AB  - Non-specific lipid-transfer proteins (nsLTPs) are capable of binding lipid
      compounds in plant tissues and are coded by the nsLTP genes. Here, we present the
      analysis of expression of a family of potato (Solanum tuberosum) nsLTP genes that
      express throughout the developing plant in a highly tissue-specific manner. Three
      transcript-derived fragments were isolated using an amplified restriction
      fragment polymorphism-derived technique for RNA fingerprinting that show homology
      to plant nsLTP genes. These transcript-derived fragments displayed modulated
      expression profiles related to the development of new tissues, with a peak of
      transcription around the time of tuberization and just prior to sprout
      development, at dormancy breakage. In addition, a homologous family of expressed
      sequence tags was identified whose individual members could be classified
      according to their tissue specificity. Two subgroups of expressed sequence tags
      were found to express during tuber life cycle. To study the regulation of potato
      nsLTP genes, two putative potato nsLTP promoters were isolated and their
      expression was studied using promoter-marker-gene fusions. The results showed
      that one of the two promoters directed a highly specific pattern of expression
      detected in the phloem surrounding the nodes of young plants and in the same
      tissue of tuber related organs, whereas the second putative promoter showed
      little tissue or organ specificity. This difference in expression is likely due
      to a 331-bp insertion present in the tissue-specific promoter.

PMID- 12177465
TI  - A novel plant homeodomain protein interacts in a functionally relevant manner
      with a virus movement protein.
AB  - Tomato bushy stunt virus and its cell-to-cell movement protein (MP; P22) provide
      valuable tools to study trafficking of macromolecules through plants. This study
      shows that wild-type P22 and selected movement-defective P22 amino acid
      substitution mutants were equivalent for biochemical features commonly associated
      with MPs (i.e. RNA binding, phosphorylation, and membrane partitioning). This
      generated the hypothesis that their movement defect was caused by improper
      interaction between the P22 mutants and one or more host factors. To test this,
      P22 was used as bait in a yeast (Saccharomyces cerevisiae) two-hybrid screen with
      a tobacco (Nicotiana tabacum) cDNA library, which identified a new plant
      homeodomain leucine-zipper protein that reproducibly interacted with P22 but not
      with various control proteins. These results were confirmed with an independent
      in vitro binding test. An mRNA for the host protein was detected in plants, and
      its accumulation was enhanced upon Tomato bushy stunt virus infection of two
      plant species. The significance of this interaction was further demonstrated by
      the failure of the homeodomain protein to interact efficiently with two of the
      well-defined movement-deficient P22 mutants in yeast and in vitro. This is the
      first report, to our knowledge, that a new plant homeodomain leucine-zipper
      protein interacts specifically and in a functionally relevant manner with a plant
      virus MP.

PMID- 12177464
TI  - ADP-ribosylation factor 1 of Arabidopsis plays a critical role in intracellular
      trafficking and maintenance of endoplasmic reticulum morphology in Arabidopsis.
AB  - ADP-ribosylation factors (Arf), a family of small GTP-binding proteins, play
      important roles in intracellular trafficking in animal and yeast cells. Here, we
      investigated the roles of two Arf homologs, Arf1 and Arf3 of Arabidopsis, in
      intracellular trafficking in plant cells. We generated dominant negative mutant
      forms of Arf 1 and Arf3 and examined their effect on trafficking of reporter
      proteins in protoplasts. Arf1[T31N] inhibited trafficking of H(+)-ATPase:green
      fluorescent protein (GFP) and sialyltransferase (ST):GFP to the plasma membrane
      and the Golgi apparatus. In addition, Arf1[T31N] caused relocalization of the
      Golgi reporter protein ST:GFP to the endoplasmic reticulum (ER). In protoplasts
      expressing Arf1[T31N], ST:red fluorescent protein remained in the ER, whereas
      H(+)-ATPase:GFP was mistargeted to another organelle. Also, expression of
      Arf1[T31N] in protoplasts resulted in profound changes in the morphology of the
      ER. The treatment of protoplasts with brefeldin A had exactly the same effect as
      Arf1[T31N] on various intracellular trafficking pathways. In contrast, Arf3[T31N]
      did not affect trafficking of any of these reporter proteins. Inhibition
      experiments using mutants with various domains swapped between Arf1 and Arf3
      revealed that the N-terminal domain is interchangeable for trafficking
      inhibition. However, in addition to the T31N mutation, motifs in domains II, III,
      and IV of Arf1 were necessary for inhibition of trafficking of H(+)-ATPase:GFP.
      Together, these results strongly suggest that Arf1 plays a role in the
      intracellular trafficking of cargo proteins in Arabidopsis, and that Arf1
      functions through a brefeldin A-sensitive factor.

PMID- 12177467
TI  - Activation tagging using the En-I maize transposon system in Arabidopsis.
AB  - A method for the generation of stable activation tag inserts was developed in
      Arabidopsis using the maize (Zea mays) En-I transposon system. The method employs
      greenhouse selectable marker genes that are useful to efficiently generate large
      populations of insertions. A population of about 8,300 independent stable
      activation tag inserts has been produced. Greenhouse-based screens for mutants in
      a group of plants containing about 2,900 insertions revealed about 31 dominant
      mutants, suggesting a dominant mutant frequency of about 1%. From the first batch
      of about 400 stable insertions screened in the greenhouse, four gain-in-function,
      dominant activation-tagged, morphological mutants were identified. A novel gain
      in-function mutant called thread is described, in which the target gene belongs
      to the same family as the YUCCA flavin-mono-oxygenase that was identified by T
      DNA activation tagging. The high frequency of identified gain-in-function mutants
      in the population suggests that the En-I system described here is an efficient
      strategy to saturate plant genomes with activation tag inserts. Because only a
      small number of primary transformants are required to generate an activation tag
      population, the En-I system appears to be an attractive alternative to study
      plant species where the present transformation methods have low efficiencies.

PMID- 12177466
TI  - Regulation and role of the Arabidopsis abscisic acid-insensitive 5 gene in
      abscisic acid, sugar, and stress response.
AB  - Abscisic acid (ABA) and stress response from late embryonic growth through early
      seedling development is regulated by a signaling network that includes the
      Arabidopsis ABA-insensitive (ABI)5 gene, which encodes a basic leucine zipper
      transcription factor. We have characterized genetic, developmental, and
      environmental regulation of ABI5 expression. Although expressed most strongly in
      seeds, the ABI5 promoter is also active in vegetative and floral tissue.
      Vegetative expression is strongly induced by ABA, and weakly by stress treatments
      during a limited developmental window up to approximately 2 d post
      stratification, but ABA and some stresses can induce expression in specific
      tissues at later stages. ABI5 expression is autoregulated in transgenic plants
      and yeast (Saccharomyces cerevisiae), and stress response appears to involve ABI5
      dependent and -independent mechanisms. To determine whether ABI5 is necessary
      and/or sufficient for ABA or stress response, we assayed the effects of increased
      ABI5 expression on growth and gene expression. Although overexpression of ABI5
      confers hypersensitivity to ABA and sugar, as previously described for ABI4 and
      ABI3 overexpression lines, it has relatively limited effects on enhancing ABA
      responsive gene expression. Comparison of expression of eight ABI5-homologous
      genes shows overlapping regulation by ABI3, ABI4, and ABI5, suggestive of a
      combinatorial network involving positive and negative regulatory interactions.

PMID- 12177468
TI  - Loss-of-function mutations in the ethylene receptor ETR1 cause enhanced
      sensitivity and exaggerated response to ethylene in Arabidopsis.
AB  - Ethylene signaling in Arabidopsis begins at a family of five ethylene receptors
      that regulate activity of a downstream mitogen-activated protein kinase kinase
      kinase, CTR1. Triple and quadruple loss-of-function ethylene receptor mutants
      display a constitutive ethylene response phenotype, indicating they function as
      negative regulators in this pathway. No ethylene-related phenotype has been
      described for single loss-of-function receptor mutants, although it was reported
      that etr1 loss-of-function mutants display a growth defect limiting plant size.
      In actuality, this apparent growth defect results from enhanced responsiveness to
      ethylene; a phenotype manifested in all tissues tested. The phenotype displayed
      by etr1 loss-of-function mutants was rescued by treatment with an inhibitor of
      ethylene perception, indicating that it is ethylene dependent. Identification of
      an ethylene-dependent phenotype for a loss-of-function receptor mutant gave a
      unique opportunity for genetic and biochemical analysis of upstream events in
      ethylene signaling, including demonstration that the dominant ethylene
      insensitive phenotype of etr2-1 is partially dependent on ETR1. This work
      demonstrates that mutational loss of the ethylene receptor ETR1 alters
      responsiveness to ethylene in Arabidopsis and that enhanced ethylene response in
      Arabidopsis not only results in increased sensitivity but exaggeration of
      response.

PMID- 12177469
TI  - Significance of the expression of the CER6 condensing enzyme for cuticular wax
      production in Arabidopsis.
AB  - To learn more about the role of the CER6 condensing enzyme in Arabidopsis surface
      wax production, we determined CER6 transcription domains and the timing of CER6
      transcription in vegetative and reproductive structures from juvenile, mature,
      and senescing tissues. We found that CER6 is highly transcribed throughout
      development, exclusively in the epidermal cells in all tissues examined. The only
      exception to the epidermal expression was observed in anthers nearing maturity,
      in which CER6 mRNA was localized in the tapetum. To determine if environmental
      factors such as light and water deficit, which are known to stimulate wax
      accumulation, induce CER6 transcription, we examined the effects of these factors
      on CER6 transcript abundance. Our results demonstrate that light is essential for
      CER6 transcription, and that osmotic stress and the presence of abscisic acid
      enhance CER6 transcript accumulation. CER6 promoter-directed expression of the
      beta-glucuronidase reporter gene in transgenic plants demonstrated that the CER6
      promoter was highly effective in directing epidermis-specific expression in
      Arabidopsis and tobacco (Nicotiana tabacum). Furthermore, CER6 promoter-driven
      CER6 overexpression resulted in increased wax deposition in Arabidopsis stems.
      These experiments indicate that the expression level of CER6 in the epidermis is
      one of the factors controlling wax accumulation on Arabidopsis stems.

PMID- 12177471
TI  - Complex formation of myrosinase isoenzymes in oilseed rape seeds are dependent on
      the presence of myrosinase-binding proteins.
AB  - The enzyme myrosinase (EC 3.2.3.1) degrades the secondary compounds
      glucosinolates upon wounding and serves as a defense to generalist pests in
      Capparales. Certain myrosinases are present in complexes together with other
      proteins such as myrosinase-binding proteins (MBP) in extracts of oilseed rape
      (Brassica napus) seeds. Immunhistochemical analysis of wild-type seeds showed
      that MBPs were present in most cells but not in the myrosin cells, indicating
      that the complex formation observed in extracts is initiated upon tissue
      disruption. To study the role of MBP in complex formation and defense, oilseed
      rape antisense plants lacking the seed MBPs were produced. Western blotting and
      immunohistochemical staining confirmed depletion of MBP in the transgenic seeds.
      The exclusive expression of myrosinase in idioblasts (myrosin cells) of the seed
      was not affected by the down-regulation of MBP. Using size-exclusion
      chromatography, we have shown that myrosinases with subunit molecular masses of
      62 to 70 kD were present as free dimers from the antisense seed extract, whereas
      in the wild type, they formed complexes. In accordance with this, MBPs are
      necessary for myrosinase complex formation of the 62- to 70-kD myrosinases. The
      product formed from sinalbin hydrolysis by myrosinase was the same whether MBP
      was present or not. The performance of a common beetle generalist (Tenebrio
      molitor) fed with seeds, herbivory by flea beetles (Phyllotreta undulata) on
      cotyledons, or growth rate of the Brassica fungal pathogens Alternaria brassicae
      or Lepthosphaeria maculans in the presence of seed extracts were not affected by
      the down-regulation of MBP, leaving the physiological function of this protein
      family open.

PMID- 12177470
TI  - Expression and molecular analysis of the Arabidopsis DXR gene encoding 1-deoxy-D
      xylulose 5-phosphate reductoisomerase, the first committed enzyme of the 2-C
      methyl-D-erythritol 4-phosphate pathway.
AB  - 1-Deoxy-D-xylulose 5-phosphate reductoisomerase (DXR) catalyzes the first
      committed step of the 2-C-methyl-D-erythritol 4-phosphate pathway for isoprenoid
      biosynthesis. In Arabidopsis, DXR is encoded by a single-copy gene. We have
      cloned a full-length cDNA corresponding to this gene. A comparative analysis of
      all plant DXR sequences known to date predicted an N-terminal transit peptide for
      plastids, with a conserved cleavage site, and a conserved proline-rich region at
      the N terminus of the mature protein, which is not present in the prokaryotic DXR
      homologs. We demonstrate that Arabidopsis DXR is targeted to plastids and
      localizes into chloroplasts of leaf cells. The presence of the proline-rich
      region in the mature Arabidopsis DXR was confirmed by detection with a specific
      antibody. A proof of the enzymatic function of this protein was obtained by
      complementation of an Escherichia coli mutant defective in DXR activity. The
      expression pattern of beta-glucuronidase, driven by the DXR promoter in
      Arabidopsis transgenic plants, together with the tissue distribution of DXR
      transcript and protein, revealed developmental and environmental regulation of
      the DXR gene. The expression pattern of the DXR gene parallels that of the
      Arabidopsis 1-deoxy-D-xylulose 5-phosphate synthase gene, but the former is
      slightly more restricted. These genes are expressed in most organs of the plant
      including roots, with higher levels in seedlings and inflorescences. The block of
      the 2-C-methyl-D-erythritol 4-phosphate pathway in Arabidopsis seedlings with
      fosmidomycin led to a rapid accumulation of DXR protein, whereas the 1-deoxy-D
      xylulose 5-phosphate synthase protein level was not altered. Our results are
      consistent with the participation of the Arabidopsis DXR gene in the control of
      the 2-C-methyl-D-erythritol 4-phosphate pathway.

PMID- 12177472
TI  - Overexpression of the clpP 5'-untranslated region in a chimeric context causes a
      mutant phenotype, suggesting competition for a clpP-specific RNA maturation
      factor in tobacco chloroplasts.
AB  - The plastid ribosomal RNA (rrn) operon promoter was fused with DNA segments
      encoding the leader sequence (5'-untranslated region [UTR]) of plastid mRNAs to
      compare their efficiency in mediating translation of a bacterial protein neomycin
      phosphotransferase (NPTII) in tobacco (Nicotiana tabacum) chloroplasts. In young
      leaves, NPTII accumulated at 0.26% and 0.8% of the total soluble leaf protein
      from genes with the clpP and atpB 5'-UTR, respectively. Interestingly, expression
      of NPTII from the promoter with the clpP 5'-UTR (0.26% NPTII) caused a mutant
      (chlorotic) phenotype, whereas plants accumulating approximately 0.8% NPTII from
      the atpB 5'-UTR were normal green, indicating that the mutant phenotype was
      independent of NPTII accumulation. Low levels of monocistronic clpP mRNA and
      accumulation of intron-containing clpP transcripts in the chlorotic leaves
      suggest competition between the clpP 5'-UTR in the chimeric transcript and the
      native clpP pre-mRNA (ratio 16:1) for an mRNA maturation factor. Because
      maturation of 11 other intron-containing mRNAs was unaffected in the chlorotic
      leaves, it appears that the factor is clpP specific. The mutant phenotype is
      correlated with reduced levels (approximately 2 times) of the ClpP1 protease
      subunit, supporting an important role for ClpP1 in chloroplast development.

PMID- 12177473
TI  - Inhibition of the plastidic ATP/ADP transporter protein primes potato tubers for
      augmented elicitation of defense responses and enhances their resistance against
      Erwinia carotovora.
AB  - Tubers of transgenic potato (Solanum tuberosum) plants with decreased activity of
      the plastidic ATP/ADP transporter AATP1 display reduced levels of starch,
      modified tuber morphology, and altered concentrations of primary metabolites.
      Here, we demonstrate that the spontaneous production of hydrogen peroxide, the
      endogenous content of salicylic acid, and the levels of mRNAs of various defense
      related genes are similar in tuber discs of wild-type and AATP1(St) antisense
      plants. However, upon challenging the tissue with fungal elicitors or culture
      supernatants of the soft rot-causing pathogen Erwinia carotovora subsp.
      atroseptica, the AATP1(St) antisense tubers exhibit highly potentiated activation
      of defense responses when compared with wild-type tissue. The augmented defense
      responses comprise enhanced accumulation of transcripts of five defense-related
      genes (beta-1,3-GLUCANASE B2 and A1, CHITINASE B3 and A2, and Phe AMMONIA-LYASE)
      and enhanced elicitation (up to 21-fold) of the early hydrogen peroxide burst.
      The potentiated activation of cellular defense responses in AATP1(St) antisense
      tubers is not accompanied by a precedent increase in endogenous salicylic acid
      levels, but is associated with a strongly enhanced resistance of the tissue to E.
      carotovora. From these results, we conclude that inhibition of primary metabolic
      reactions induces a primed state that sensitizes the potato tubers for improved
      elicitation of various cellular defense responses, which likely contribute to
      enhanced E. carotovora resistance.

PMID- 12177474
TI  - A role for diacylglycerol acyltransferase during leaf senescence.
AB  - Lipid analysis of rosette leaves from Arabidopsis has revealed an accumulation of
      triacylglycerol (TAG) with advancing leaf senescence coincident with an increase
      in the abundance and size of plastoglobuli. The terminal step in the biosynthesis
      of TAG in Arabidopsis is catalyzed by diacylglycerol acyltransferase 1 (DGAT1; EC
      2.3.1.20). When gel blots of RNA isolated from rosette leaves at various stages
      of development were probed with the Arabidopsis expressed sequence tag clone,
      E6B2T7, which has been annotated as DGAT1, a steep increase in DGAT1 transcript
      levels was evident in the senescing leaves coincident with the accumulation of
      TAG. The increase in DGAT1 transcript correlated temporally with enhanced levels
      of DGAT1 protein detected immunologically. Two lines of evidence indicated that
      the TAG of senescing leaves is synthesized in chloroplasts and sequesters fatty
      acids released from the catabolism of thylakoid galactolipids. First, TAG
      isolated from senescing leaves proved to be enriched in hexadecatrienoic acid
      (16:3) and linolenic acid (18:3), which are normally present in thylakoid
      galactolipids. Second, DGAT1 protein in senescing leaves was found to be
      associated with chloroplast membranes. These findings collectively indicate that
      diacylglycerol acyltransferase plays a role in senescence by sequestering fatty
      acids de-esterified from galactolipids into TAG. This would appear to be an
      intermediate step in the conversion of thylakoid fatty acids to phloem-mobile
      sucrose during leaf senescence.

PMID- 12177475
TI  - Reactive oxygen species in the elongation zone of maize leaves are necessary for
      leaf extension.
AB  - The production and role of reactive oxygen species (ROS) in the expanding zone of
      maize (Zea mays) leaf blades were investigated. ROS release along the leaf blade
      was evaluated by embedding intact seedlings in 2',7'-dichlorofluorescein
      containing agar and examining the distribution of 2',7'-dichlorofluorescein
      fluorescence along leaf 4, which was exposed by removing the outer leaves before
      embedding the seedling. Fluorescence was high in the expanding region, becoming
      practically non-detectable beyond 65 mm from the ligule, indicating high ROS
      production in the expansion zone. Segments obtained from the elongation zone of
      leaf 4 were used to assess the role of ROS in leaf elongation. The distribution
      of cerium perhydroxide deposits in electron micrographs indicated hydrogen
      peroxide (H(2)O(2)) presence in the apoplast. 2',7'-Dichlorofluorescein
      fluorescence and apoplastic H(2)O(2) accumulation were inhibited with
      diphenyleneiodonium (DPI), which also inhibited O*(2)(-) generation, suggesting a
      flavin-containing enzyme activity such as NADPH oxidase was involved in ROS
      production. Segments from the elongation zone incubated in water grew 8% in 2 h.
      KI treatments, which scavenged H(2)O(2) but did not inhibit O*(2)(-) production,
      did not modify growth. DPI significantly inhibited segment elongation, and the
      addition of H(2)O(2) (50 or 500 microM) to the incubation medium partially
      reverted the inhibition caused by DPI. These results indicate that a certain
      concentration of H(2)O(2) is necessary for leaf elongation, but it could not be
      distinguished whether H(2)O(2), or other ROS, are the actual active agents.

PMID- 12177476
TI  - Independent activation of cold acclimation by low temperature and short
      photoperiod in hybrid aspen.
AB  - Temperate zone woody plants cold acclimate in response to both short daylength
      (SD) and low temperature (LT). We were able to show that these two environmental
      cues induce cold acclimation independently by comparing the wild type (WT) and
      the transgenic hybrid aspen (Populus tremula x Populus tremuloides Michx.) line
      22 overexpressing the oat (Avena sativa) PHYTOCHROME A gene. Line 22 was not able
      to detect the SD and, consequently, did not stop growing in SD conditions. This
      resulted in an impaired freezing tolerance development under SD. In contrast,
      exposure to LT resulted in cold acclimation of line 22 to a degree comparable
      with the WT. In contrast to the WT, line 22 could not dehydrate the overwintering
      tissues or induce the production of dehydrins (DHN) under SD conditions.
      Furthermore, abscisic acid (ABA) content of the buds of line 22 were the same
      under SD and long daylength, whereas prolonged SD exposure decreased the ABA
      level in the WT. LT exposure resulted in a rapid accumulation of DHN in both the
      WT and line 22. Similarly, ABA content increased transiently in both the WT and
      line 22. Our results indicate that phytochrome A is involved in photoperiodic
      regulation of ABA and DHN levels, but at LT they are regulated by a different
      mechanism. Although SD and LT induce cold acclimation independently, ABA and DHN
      may play important roles in both modes of acclimation.

PMID- 12177478
TI  - Seasonal changes of plasma membrane H(+)-ATPase and endogenous ion current during
      cambial growth in poplar plants.
AB  - The plasma membrane H(+)-ATPase (PM H(+)-ATPase), potassium ions, and endogenous
      ion currents might play a fundamental role in the physiology of cambial growth.
      Seasonal changes of these parameters were studied in twigs of Populus nigra and
      Populus trichocarpa. Monoclonal and polyclonal antibodies against the PM H(+)
      ATPase, x-ray analysis for K(+) localization and a vibrating electrode for
      measurement of endogenous ion currents were used as probes. In dormant plants
      during autumn and winter, only a slight immunoreactivity against the PM H(+)
      ATPase was found in cross sections and tissue homogenates, K(+) was distributed
      evenly, and the density of endogenous current was low. In spring during cambial
      growth, strong immunoreactivity against a PM H(+)-ATPase was observed in cambial
      cells and expanding xylem cells using the monoclonal antibody 46 E5 B11 F6 for
      fluorescence microscopy and transmission electron microscopy. At the same time,
      K(+) accumulated in cells of the cambial region, and strong endogenous current
      was measured in the cambial and immature xylem zone. Addition of auxin to dormant
      twigs induced the formation of this PM H(+)-ATPase in the dormant cambial region
      within a few days and an increase in density of endogenous current in shoot
      cuttings within a few hours. The increase in PM H(+)-ATPase abundance and in
      current density by auxin indicates that auxin mediates a rise in number and
      activity of an H(+)-ATPase in the plasma membrane of cambial cells and their
      derivatives. This PM H(+)-ATPase generates the necessary H(+)-gradient (proton
      motive force) for the uptake of K(+) and nutrients into cambial and expanding
      xylem cells.

PMID- 12177477
TI  - Nitric oxide acts as an antioxidant and delays programmed cell death in barley
      aleurone layers.
AB  - Nitric oxide (NO) is a freely diffusible, gaseous free radical and an important
      signaling molecule in animals. In plants, NO influences aspects of growth and
      development, and can affect plant responses to stress. In some cases, the effects
      of NO are the result of its interaction with reactive oxygen species (ROS). These
      interactions can be cytotoxic or protective. Because gibberellin (GA)-induced
      programmed cell death (PCD) in barley (Hordeum vulgare cv Himalaya) aleurone
      layers is mediated by ROS, we examined the effects of NO donors on PCD and ROS
      metabolizing enzymes in this system. NO donors delay PCD in layers treated with
      GA, but do not inhibit metabolism in general, or the GA-induced synthesis and
      secretion of alpha-amylase. alpha-Amylase secretion is stimulated slightly by NO
      donors. The effects of NO donors are specific for NO, because they can be blocked
      completely by the NO scavenger 2-(4-carboxyphenyl)-4,4,5,5-tetramethylimidazoline
      1-oxyl-3-oxide. The antioxidant butylated hydroxy toluene also slowed PCD, and
      these data support our hypothesis that NO is a protective antioxidant in aleurone
      cells. The amounts of CAT and SOD, two enzymes that metabolize ROS, are greatly
      reduced in aleurone layers treated with GA. Treatment with GA in the presence of
      NO donors delays the loss of CAT and SOD. We speculate that NO may be an
      endogenous modulator of PCD in barley aleurone cells.

PMID- 12177479
TI  - In vivo and in vitro phosphorylation of membrane and soluble forms of soybean
      nodule sucrose synthase.
AB  - Sucrose synthase (SS) is a known phosphoserine (SerP)-containing enzyme in a
      variety of plant "sink" organs, including legume root nodules, where it is
      phosphorylated primarily at Ser-11. Using immunofluorescence confocal microscopy,
      we documented that part of the total SS (nodulin-100) pool in mature soybean
      (Glycine max) nodules is apparently associated with the plasma membrane in situ,
      and we report that this association is very "tight," as evidenced by a variety of
      chemical and enzymatic pretreatments of the isolated microsomal fraction. To
      investigate the in situ and in planta phosphorylation state of the membrane (m)
      and soluble (s) forms of nodule SS, three complementary approaches were used.
      First, excised nodules were radiolabeled in situ with [(32)P]Pi for subsequent
      analysis of phosphorylated m- and s-SS; second, immunopurified s- and m-SS were
      used as substrate in "on-bead" assays of phosphorylation by nodule Ca(2+)
      dependent protein kinase; and third, SS-Ser-11(P) phosphopeptide-specific
      antibodies were developed and used. The collective results provide convincing
      evidence that microsomal nodulin-100 is phosphorylated in mature nodules, and
      that it is hypophosphorylated relative to s-SS (on an equivalent SS protein
      basis) in attached, unstressed nodules. Moreover, the immunological data and
      related phosphopeptide mapping analyses indicate that a homologous N-terminal
      seryl-phosphorylation domain and site reside in microsomal nodulin-100. We also
      observed that mild, short-term inorganic nitrogen and salt stresses have a
      significant negative impact on the content and N-terminal phosphorylation state
      of nodule m- and s-SS, with the former being the more sensitive of the two SS
      forms.

PMID- 12177481
TI  - Linamarase expression in cassava cultivars with roots of low- and high-cyanide
      content.
AB  - This paper reports the expression and localization of linamarase in roots of two
      cassava (Manihot esculenta Crantz) cultivars of low and high cyanide. Two
      different patterns of linamarase activity were observed. In the low-cyanide type,
      young leaves displayed very high enzyme activity during the early plant growing
      stage (3 months), whereas in root peel, the activity increased progressively to
      reach a peak in 11-month-old plants. Conversely, in the high-cyanide cultivar
      (HCV), root peel linamarase activity decreased during the growth cycle, whereas
      in expanded leaves linamarase activity peaked in 11-month-old plants. The
      accumulation of linamarin showed a similar pattern in both cultivars, although a
      higher concentration was always found in the HCV. Linamarase was found mainly in
      laticifer cells of petioles and roots of both cultivars with no significant
      differences between them. At the subcellular level, there were sharp differences
      because linamarase was found mainly in the cell walls of the HCV, whereas in the
      low-cyanide cultivar, the enzyme was present in vacuoles and cell wall of
      laticifer cells. Reverse transcriptase-PCR on cassava tissues showed no
      expression of linamarase in cassava roots, thus, the transport of linamarase from
      shoots to roots through laticifers is proposed.

PMID- 12177480
TI  - The out of phase 1 mutant defines a role for PHYB in circadian phase control in
      Arabidopsis.
AB  - Arabidopsis displays circadian rhythms in stomatal aperture, stomatal
      conductance, and CO(2) assimilation, each of which peaks around the middle of the
      day. The rhythmic opening and closing of stomata confers a rhythm in sensitivity
      and resistance, respectively, to the toxic gas sulfur dioxide. Using this
      physiological assay as a basis for a mutant screen, we isolated mutants with
      defects in circadian timing. Here, we characterize one mutant, out of phase 1
      (oop1), with the circadian phenotype of altered phase. That is, the timing of the
      peak (acrophase) of multiple circadian rhythms (leaf movement, CO(2)
      assimilation, and LIGHT-HARVESTING CHLOROPHYLL a/b-BINDING PROTEIN transcription)
      is early with respect to wild type, although all circadian rhythms retain normal
      period length. This is the first such mutant to be characterized in Arabidopsis.
      oop1 also displays a strong photoperception defect in red light characteristic of
      phytochrome B (phyB) mutants. The oop1 mutation is a nonsense mutation of PHYB
      that results in a truncated protein of 904 amino acids. The defect in circadian
      phasing is seen in seedlings entrained by a light-dark cycle but not in seedlings
      entrained by a temperature cycle. Thus, PHYB contributes light information
      critical for proper determination of circadian phase.

PMID- 12177482
TI  - A new resource of locally transposed Dissociation elements for screening gene
      knockout lines in silico on the Arabidopsis genome.
AB  - We transposed Dissociation (Ds) elements from three start loci on chromosome 5 in
      Arabidopsis (Nossen ecotype) by using a local transposition system. We determined
      partial genomic sequences flanking the Ds elements and mapped the elements'
      insertion sites in 1,173 transposed lines by comparison with the published
      genomic sequence. Most of the lines contained a single copy of the Ds element.
      One-half of the lines contained Ds on chromosome 5; in particular, insertion "hot
      spots" near the three start loci were clearly observed. In the other lines, the
      Ds elements were transposed across chromosomes. We found other insertion hot
      spots at the tops of chromosomes 2 and 4, near nucleolus organizer regions 2 and
      4, respectively. Another characteristic feature was that the Ds elements tended
      to transpose near the chromosome ends and rarely transposed near centromeres. The
      distribution patterns differed among the three start loci, even though they
      possessed the same Ds construct. More than one-half of the Ds elements were
      inserted irregularly into the genome; that is, they did not retain the perfect
      inverted repeat sequence of Ds nor leave perfect target site duplications. This
      precise analysis of distribution patterns will contribute to a comprehensive
      understanding of the transposing mechanism. From these Ds insertion sites, we
      have constructed a database for screening gene-knockout mutants in silico. In 583
      of the 1,173 lines, the Ds elements were inserted into protein-coding genes,
      which suggests that these lines are gene-knockout mutants. The database and
      individual lines will be available freely for academic use from the RIKEN Bio
      Resource Center (http://www.brc.riken.go.jp/Eng/index.html).

PMID- 12177483
TI  - Fatty acid export from the chloroplast. Molecular characterization of a major
      plastidial acyl-coenzyme A synthetase from Arabidopsis.
AB  - Acyl-coenzyme A (CoA) synthetases (ACSs, EC 6.2.1.3) catalyze the formation of
      fatty acyl-CoAs from free fatty acid, ATP, and CoA. Essentially all de novo fatty
      acid synthesis occurs in the plastid. Fatty acids destined for membrane
      glycerolipid and triacylglycerol synthesis in the endoplasmic reticulum must be
      first activated to acyl-CoAs via an ACS. Within a family of nine ACS genes from
      Arabidopsis, we identified a chloroplast isoform, LACS9. LACS9 is highly
      expressed in developing seeds and young rosette leaves. Both in vitro chloroplast
      import assays and transient expression of a green fluorescent protein fusion
      indicated that the LACS9 protein is localized in the plastid envelope. A T-DNA
      knockout mutant (lacs9-1) was identified by reverse genetics and these mutant
      plants were indistinguishable from wild type in growth and appearance. Analysis
      of leaf lipids provided no evidence for compromised export of acyl groups from
      chloroplasts. However, direct assays demonstrated that lacs9-1 plants contained
      only 10% of the chloroplast long-chain ACS activity found for wild type. The
      residual long-chain ACS activity in mutant chloroplasts was comparable with
      calculated rates of fatty acid synthesis. Although another isozyme contributes to
      the activation of fatty acids during their export from the chloroplast, LACS9 is
      a major chloroplast ACS.

PMID- 12177485
TI  - hpRNA-mediated targeting of the Arabidopsis FAD2 gene gives highly efficient and
      stable silencing.
AB  - The endogenous Delta 12-desaturase gene (FAD2) in Arabidopsis was targeted for
      silencing using seed-specific cosuppression (CS), hairpin (HP) RNA (hpRNA), and
      intron-spliced HP (iHP) constructs. The iHP construct, incorporating the 120-bp
      3'-untranslated region of the FAD2 gene, gave the highest degree of silencing. In
      some iHP lines Delta 12-desaturase activity was reduced to levels as low as those
      in the null fad2-1 mutant, and every primary transformant showed a pronounced
      reduction in FAD2 activity. One highly silenced iHP line was propagated for five
      generations and showed no reversion or diminution in its degree of silencing.
      About 75% of plants transformed with the HP construct, targeting the FAD2 coding
      region, gave dramatically reduced Delta 12-desaturase activity, whereas
      approximately 50% of plants transformed with the CS construct, containing the
      same coding region sequence, showed silencing at a much less profound level. In
      all three types of constructs, the degree of silencing was increased when the
      transgenes were homozygous, but this was much more pronounced for the CS
      constructs. All three types of construct could give a single locus that was
      capable of effective silencing, but in the one such CS line where this was the
      case, the locus had a complex insertion pattern. This is consistent with the
      concept that posttranscriptional gene silencing is induced by double-stranded, or
      self-complementary, RNA that is formed in cases of CS by complex insertion
      patterns at a single locus and that the most effective way of generating
      profoundly silenced plants is by the use of constructs that encode hpRNAs.
      Furthermore, these results demonstrate for the first time, to our knowledge, that
      iHP constructs targeted against an endogenous seed-expressed gene are clearly
      able to generate phenotypic changes that are inherited stably over several
      generations, making this approach a reliable technique for genetic modification
      of seed quality and possibly other traits in agricultural plants.

PMID- 12177484
TI  - Arabidopsis contains nine long-chain acyl-coenzyme a synthetase genes that
      participate in fatty acid and glycerolipid metabolism.
AB  - Long-chain acyl-coenzyme A (CoA) synthetases (LACSs) activate free fatty acids to
      acyl-CoA thioesters and as such play critical roles in fatty acid metabolism.
      This important class of enzymes factors prominently in several fatty acid-derived
      metabolic pathways, including phospholipid, triacylglycerol, and jasmonate
      biosynthesis and fatty acid beta-oxidation. In an effort to better understand the
      factors that control fatty acid metabolism in oilseeds, we have sought to
      identify and characterize genes that encode LACSs in Arabidopsis. Nine cDNAs were
      identified, cloned, and tested for their ability to complement a LACS-deficient
      strain of yeast (Saccharomyces cerevisiae). Seven of the nine successfully
      restored growth, whereas two cDNAs encoding putative peroxisomal isoforms did
      not. Lysates from yeast cells overexpressing each of the nine cDNAs were active
      in LACS enzyme assays using oleic acid as a substrate. The substrate
      specificities of the enzymes were determined after overexpression in LACS
      deficient Escherichia coli. Most of the LACS enzymes displayed highest levels of
      activity with the fatty acids that make up the common structural and storage
      lipids in Arabidopsis tissues. Analysis of the tissue-specific expression
      profiles for these genes revealed one flower-specific isoform, whereas all others
      were expressed in various tissues throughout the plant. These nine cDNAs are
      thought to constitute the entire LACS family in Arabidopsis, and as such, will
      serve as powerful tools in the study of acyl-CoA metabolism in oilseeds.

PMID- 12177486
TI  - High-stearic and High-oleic cottonseed oils produced by hairpin RNA-mediated post
      transcriptional gene silencing.
AB  - We have genetically modified the fatty acid composition of cottonseed oil using
      the recently developed technique of hairpin RNA-mediated gene silencing to down
      regulate the seed expression of two key fatty acid desaturase genes, ghSAD-1
      encoding stearoyl-acyl-carrier protein Delta 9-desaturase and ghFAD2-1-encoding
      oleoyl-phosphatidylcholine omega 6-desaturase. Hairpin RNA-encoding gene
      constructs (HP) targeted against either ghSAD-1 or ghFAD2-1 were transformed into
      cotton (Gossypium hirsutum cv Coker 315). The resulting down-regulation of the
      ghSAD-1 gene substantially increased stearic acid from the normal levels of 2% to
      3% up to as high as 40%, and silencing of the ghFAD2-1 gene resulted in greatly
      elevated oleic acid content, up to 77% compared with about 15% in seeds of
      untransformed plants. In addition, palmitic acid was significantly lowered in
      both high-stearic and high-oleic lines. Similar fatty acid composition phenotypes
      were also achieved by transformation with conventional antisense constructs
      targeted against the same genes, but at much lower frequencies than were achieved
      with the HP constructs. By intercrossing the high-stearic and high-oleic
      genotypes, it was possible to simultaneously down-regulate both ghSAD-1 and
      ghFAD2-1 to the same degree as observed in the individually silenced parental
      lines, demonstrating for the first time, to our knowledge, that duplex RNA
      induced posttranslational gene silencing in independent genes can be stacked
      without any diminution in the degree of silencing. The silencing of ghSAD-1
      and/or ghFAD2-1 to various degrees enables the development of cottonseed oils
      having novel combinations of palmitic, stearic, oleic, and linoleic contents that
      can be used in margarines and deep frying without hydrogenation and also
      potentially in high-value confectionery applications.

PMID- 12177488
TI  - Down-regulation of tomato beta-galactosidase 4 results in decreased fruit
      softening.
AB  - Transcript abundance of the gene encoding beta-galactosidase II, a beta
      galactosidase/exo-galactanase (EC 3.2.1.23) present during tomato (Lycopersicon
      esculentum) fruit ripening, was suppressed by expression of an antisense tomato
      beta-galactosidase 4 (TBG4) cDNA driven by the cauliflower mosaic virus 35S
      promoter. RNA gel-blot analysis was used to evaluate TBG4 mRNA levels in
      transgenic fruit. All of the antisense lines had attenuated TBG4 mRNA levels in
      turning stage fruit; however, TBG4 mRNA suppression was unstable, and mRNA levels
      varied in red-ripe fruit among the lines. Suppression of TBG4 mRNA levels in
      antisense fruit was correlated with a reduction in extractable exo-galactanase
      activity against a lupin galactan. All of the antisense lines had reduced free
      galactose levels at mature green stage 4, but levels comparable with controls
      during ripening. Total cell wall galactosyl contents in the antisense fruit were
      not significantly different from control fruit. Whole-fruit firmness was measured
      using a texture analyzer and the means of the peak force measurements for four of
      six antisense lines were significantly higher than control fruit. One antisense
      line had red-ripe fruit that were 40% firmer than controls. Fruit from this
      antisense line also had the lowest TBG4 mRNA and exo-galactanase levels and the
      highest wall galactosyl content during the early stages of ripening, implicating
      an involvement of this gene product in cell wall modification leading to fruit
      softening.

PMID- 12177487
TI  - Expression of a heterologous S-adenosylmethionine decarboxylase cDNA in plants
      demonstrates that changes in S-adenosyl-L-methionine decarboxylase activity
      determine levels of the higher polyamines spermidine and spermine.
AB  - We posed the question of whether steady-state levels of the higher polyamines
      spermidine and spermine in plants can be influenced by overexpression of a
      heterologous cDNA involved in the later steps of the pathway, in the absence of
      any further manipulation of the two synthases that are also involved in their
      biosynthesis. Transgenic rice (Oryza sativa) plants engineered with the
      heterologous Datura stramonium S-adenosylmethionine decarboxylase (samdc) cDNA
      exhibited accumulation of the transgene steady-state mRNA. Transgene expression
      did not affect expression of the orthologous samdc gene. Significant increases in
      SAMDC activity translated to a direct increase in the level of spermidine, but
      not spermine, in leaves. Seeds recovered from a number of plants exhibited
      significant increases in spermidine and spermine levels. We demonstrate that
      overexpression of the D. stramonium samdc cDNA in transgenic rice is sufficient
      for accumulation of spermidine in leaves and spermidine and spermine in seeds.
      These findings suggest that increases in enzyme activity in one of the two
      components of the later parts of the pathway leading to the higher polyamines is
      sufficient to alter their levels mostly in seeds and, to some extent, in
      vegetative tissue such as leaves. Implications of our results on the design of
      rational approaches for the modulation of the polyamine pathway in plants are
      discussed in the general framework of metabolic pathway engineering.

PMID- 12177489
TI  - Inhibition of phosphate uptake in corn roots by aluminum-fluoride complexes.
AB  - F forms stable complexes with Al at conditions found in the soil. Fluoroaluminate
      complexes (AlF(x)) have been widely described as effective analogs of inorganic
      phosphate (Pi) in Pi-binding sites of several proteins. In this work, we explored
      the possibility that the phytotoxicity of AlF(x) reflects their activity as Pi
      analogs. For this purpose, (32)P-labeled phosphate uptake by excised roots and
      plasma membrane H(+)-ATPase activity were investigated in an Al-tolerant variety
      of maize (Zea mays L. var. dwarf hybrid), either treated or not with AlF(x). In
      vitro, AlF(x) competitively inhibited the rate of root phosphate uptake as well
      as the H(+)-ATPase activity. Conversely, pretreatment of seedlings with AlF(x) in
      vivo promoted no effect on the H(+)-ATPase activity, whereas a biphasic effect on
      Pi uptake by roots was observed. Although the initial rate of phosphate uptake by
      roots was inhibited by AlF(x) pretreatment, this situation changed over the
      following minutes as the rate of uptake increased and a pronounced stimulation in
      subsequent (32)Pi uptake was observed. This kinetic behavior suggests a
      reversible and competitive inhibition of the phosphate transporter by
      fluoroaluminates. The stimulation of root (32)Pi uptake induced by AlF(x)
      pretreatment was tentatively interpreted as a phosphate starvation response. This
      report places AlF(3) and AlF(4)(-) among Al-phytotoxic species and suggests a
      mechanism of action where the accumulation of Pi-mimicking fluoroaluminates in
      the soil may affect the phosphate absorption by plants. The biochemical,
      physiological, and environmental significance of these findings is discussed.

PMID- 12177491
TI  - Barley Cbf3 gene identification, expression pattern, and map location.
AB  - Although cold and drought adaptation in cereals and other plants involve the
      induction of a large number of genes, inheritance studies in Triticeae (wheat
      [Triticum aestivum], barley [Hordeum vulgare], and rye [Secale cereale]) have
      revealed only a few major loci for frost or drought tolerance that are consistent
      across multiple genetic backgrounds and environments. One might imagine that
      these loci could encode highly conserved regulatory factors that have global
      effects on gene expression; therefore, genes encoding central regulators
      identified in other plants might be orthologs of these Triticeae stress tolerance
      genes. The CBF/DREB1 regulators, identified originally in Arabidopsis as key
      components of cold and drought regulation, merit this consideration. We
      constructed barley cDNA libraries, screened these libraries and a barley
      bacterial artificial chromosome library using rice (Oryza sativa) and barley Cbf
      probes, found orthologs of Arabidopsis CBF/DREB1 genes, and examined the
      expression and genetic map location of the barley Cbf3 gene, HvCbf3. HvCbf3 was
      induced by a chilling treatment. HvCbf3 is located on barley chromosome 5H
      between markers WG364b and saflp58 on the barley cv Dicktoo x barley cv Morex
      genetic linkage map. This position is some 40 to 50 cM proximal to the winter
      hardiness quantitative trait locus that includes the Vrn-1H gene, but may
      coincide with the wheat 5A Rcg1 locus, which governs the threshold temperature at
      which cor genes are induced. From this, it remains possible that HvCbf3 is the
      basis of a minor quantitative trait locus in some genetic backgrounds, though
      that possibility remains to be thoroughly explored.

PMID- 12177490
TI  - Sensitivity of photosynthesis in a C4 plant, maize, to heat stress.
AB  - Our objective was to determine the sensitivity of components of the
      photosynthetic apparatus of maize (Zea mays), a C4 plant, to high temperature
      stress. Net photosynthesis (Pn) was inhibited at leaf temperatures above 38
      degrees C, and the inhibition was much more severe when the temperature was
      increased rapidly rather than gradually. Transpiration rate increased
      progressively with leaf temperature, indicating that inhibition was not
      associated with stomatal closure. Nonphotochemical fluorescence quenching (qN)
      increased at leaf temperatures above 30 degrees C, indicating increased thylakoid
      energization even at temperatures that did not inhibit Pn. Compared with CO(2)
      assimilation, the maximum quantum yield of photosystem II (F(v)/F(m)) was
      relatively insensitive to leaf temperatures up to 45 degrees C. The activation
      state of phosphoenolpyruvate carboxylase decreased marginally at leaf
      temperatures above 40 degrees C, and the activity of pyruvate phosphate dikinase
      was insensitive to temperature up to 45 degrees C. The activation state of
      Rubisco decreased at temperatures exceeding 32.5 degrees C, with nearly complete
      inactivation at 45 degrees C. Levels of 3-phosphoglyceric acid and ribulose-1,5
      bisphosphate decreased and increased, respectively, as leaf temperature
      increased, consistent with the decrease in Rubisco activation. When leaf
      temperature was increased gradually, Rubisco activation acclimated in a similar
      manner as Pn, and acclimation was associated with the expression of a new
      activase polypeptide. Rates of Pn calculated solely from the kinetics of Rubisco
      were remarkably similar to measured rates if the calculation included adjustment
      for temperature effects on Rubisco activation. We conclude that inactivation of
      Rubisco was the primary constraint on the rate of Pn of maize leaves as leaf
      temperature increased above 30 degrees C.

PMID- 12177492
TI  - Identification of a soybean protein that interacts with GAGA element dinucleotide
      repeat DNA.
AB  - Dinucleotide repeat DNA with the pattern (GA)(n)/(TC)(n), so-called GAGA
      elements, control gene expression in animals, and are recognized by a specific
      regulatory protein. Here, a yeast one-hybrid screen was used to isolate soybean
      (Glycine max) cDNA encoding a GAGA-binding protein (GBP) that binds to
      (GA)(n)/(CT)(n) DNA. Soybean GBP was dissimilar from the GAGA factor of
      Drosophila melanogaster. Recombinant GBP protein did not bind to dinucleotide
      repeat sequences other than (GA)(n)/(CT)(n). GBP bound to the promoter of the
      heme and chlorophyll synthesis gene Gsa1, which contains a GAGA element. Removal
      of that GAGA element abrogated binding of GBP to the promoter. Furthermore,
      insertion of the GAGA element to a nonspecific DNA conferred GBP-binding activity
      on that DNA. Thus, the GAGA element of the Gsa1 promoter is both necessary and
      sufficient for GBP binding. Gbp mRNA was expressed in leaves and was induced in
      symbiotic root nodules elicited by the bacterium Bradyrhizobium japonicum. In
      addition, Gbp transcripts were much higher in leaves of dark-treated etiolated
      plantlets than in those exposed to light for 24 h. Homologs of GBP were found in
      other dicots and in the monocot rice (Oryza sativa), as well. We suggest that
      interaction between GAGA elements and GBP-like proteins is a regulatory feature
      in plants.

PMID- 12177493
TI  - Up-regulation of phosphoinositide metabolism in tobacco cells constitutively
      expressing the human type I inositol polyphosphate 5-phosphatase.
AB  - To evaluate the impact of suppressing inositol 1,4,5-trisphosphate (InsP(3)) in
      plants, tobacco (Nicotiana tabacum) cells were transformed with the human type I
      inositol polyphosphate 5-phosphatase (InsP 5-ptase), an enzyme which specifically
      hydrolyzes InsP(3). The transgenic cell lines showed a 12- to 25-fold increase in
      InsP 5-ptase activity in vitro and a 60% to 80% reduction in basal InsP(3)
      compared with wild-type cells. Stimulation with Mas-7, a synthetic analog of the
      wasp venom peptide mastoparan, resulted in an approximately 2-fold increase in
      InsP(3) in both wild-type and transgenic cells. However, even with stimulation,
      InsP(3) levels in the transgenic cells did not reach wild-type basal values,
      suggesting that InsP(3) signaling is compromised. Analysis of whole-cell lipids
      indicated that phosphatidylinositol 4,5-bisphosphate (PtdInsP(2)), the lipid
      precursor of InsP(3), was greatly reduced in the transgenic cells. In vitro
      assays of enzymes involved in PtdInsP(2) metabolism showed that the activity of
      the PtdInsP(2)-hydrolyzing enzyme phospholipase C was not significantly altered
      in the transgenic cells. In contrast, the activity of the plasma membrane PtdInsP
      5 kinase was increased by approximately 3-fold in the transgenic cells. In vivo
      labeling studies revealed a greater incorporation of (32)P into PtdInsP(2) in the
      transgenic cells compared with the wild type, indicating that the rate of
      PtdInsP(2) synthesis was increased. These studies show that the constitutive
      expression of the human type I InsP 5-ptase in tobacco cells leads to an up
      regulation of the phosphoinositide pathway and highlight the importance of
      PtdInsP(2) synthesis as a regulatory step in this system.

PMID- 12177494
TI  - The Role of auxin, pH, and stress in the activation of embryogenic cell division
      in leaf protoplast-derived cells of alfalfa.
AB  - Culturing leaf protoplast-derived cells of the embryogenic alfalfa (Medicago
      sativa subsp. varia A2) genotype in the presence of low (1 microM) or high (10
      microM) 2, 4-dichlorophenoxyacetic acid (2,4-D) concentrations results in
      different cell types. Cells exposed to high 2,4-D concentration remain small with
      dense cytoplasm and can develop into proembryogenic cell clusters, whereas
      protoplasts cultured at low auxin concentration elongate and subsequently die or
      form undifferentiated cell colonies. Fe stress applied at nonlethal
      concentrations (1 mM) in the presence of 1 microM 2,4-D also resulted in the
      development of the embryogenic cell type. Although cytoplasmic alkalinization was
      detected during cell activation of both types, embryogenic cells could be
      characterized by earlier cell division, a more alkalic vacuolar pH, and
      nonfunctional chloroplasts as compared with the elongated, nonembryogenic cells.
      Buffering of the 10 microM 2,4-D-containing culture medium by 10 mM 2-(N
      morpholino)ethanesulfonic acid delayed cell division and resulted in
      nonembryogenic cell-type formation. The level of endogenous indoleacetic acid
      (IAA) increased transiently in all protoplast cultures during the first 4 to 5 d,
      but an earlier peak of IAA accumulation correlated with the earlier activation of
      the division cycle in embryogenic-type cells. However, this IAA peak could also
      be delayed by buffering of the medium pH by 2-(N-morpholino)ethanesulfonic acid.
      Based on the above data, we propose the involvement of stress responses,
      endogenous auxin synthesis, and the establishment of cellular pH gradients in the
      formation of the embryogenic cell type.

PMID- 12177495
TI  - A thapsigargin-sensitive Ca(2+) pump is present in the pea Golgi apparatus
      membrane.
AB  - The Golgi apparatus behaves as a bona fide Ca(2+) store in animal cells and yeast
      (Saccharomyces cerevisiae); however, it is not known whether this organelle plays
      a similar role in plant cells. In this work, we investigated the presence of an
      active Ca(2+) accumulation mechanism in the plant cell Golgi apparatus. Toward
      this end, we measured Ca(2+) uptake in subcellular fractions isolated from the
      elongating zone of etiolated pea (Pisum sativum) epicotyls. Separation of
      organelles using sucrose gradients showed a strong correlation between the
      distribution of an ATP-dependent Ca(2+) uptake activity and the Golgi apparatus
      marker enzyme, xyloglucan-fucosyltransferase. The kinetic parameters obtained for
      this activity were: the rate of maximum Ca(2+) uptake of 2.5 nmol mg min(-1) and
      an apparent K(m) for Ca(2+) of 209 nM. The ATP-dependent Ca(2+) uptake was
      strongly inhibited by vanadate (inhibitor concentration causing 50% inhibition
      [I(50)] = 126 microM) and cyclopiazonic acid (I(50) = 0.36 nmol mg protein(-1))
      and was not stimulated by calmodulin (1 microM). Addition of Cd(2+) and Cu(2+) at
      nanomolar concentration inhibited the Ca(2+) uptake, whereas Mn(2+), Fe(2+), and
      Co(2+) had no significant effect. Interestingly, the active calcium uptake was
      inhibited by thapsigargin (apparent I(50) = 88 nM), a well-known inhibitor of the
      endoplasmic reticulum and Golgi sarco-endoplasmic reticulum Ca(2+) ATPase from
      mammalian cells. A thapsigargin-sensitive Ca(2+) uptake activity was also
      detected in a cauliflower (Brassica oleracea) Golgi-enriched fraction, suggesting
      that other plants may also possess thapsigargin-sensitive Golgi Ca(2+) pumps. To
      our knowledge, this is the first report of a plant Ca(2+) pump activity that
      shows sensitivity to low concentrations of thapsigargin.

PMID- 12177497
TI  - How closely do the delta(13)C values of Crassulacean Acid metabolism plants
      reflect the proportion of CO(2) fixed during day and night?
AB  - The extent to which Crassulacean acid metabolism (CAM) plant delta(13)C values
      provide an index of the proportions of CO(2) fixed during daytime and nighttime
      was assessed. Shoots of seven CAM species (Aloe vera, Hylocereus monocanthus,
      Kalanchoe beharensis, Kalanchoe daigremontiana, Kalanchoe pinnata, Vanilla
      pauciflora, and Xerosicyos danguyi) and two C(3) species (teak [Tectona grandis]
      and Clusia sp.) were grown in a cuvette, and net CO(2) exchange was monitored for
      up to 51 d. In species exhibiting net dark CO(2) fixation, between 14% and 73.3%
      of the carbon gain occurred in the dark. delta(13)C values of tissues formed
      inside the cuvette ranged between -28.7 per thousand and -11.6 per thousand, and
      correlated linearly with the percentages of carbon gained in the light and in the
      dark. The delta(13)C values for new biomass obtained solely during the dark and
      light were estimated as -8.7 per thousand and -26.9 per thousand, respectively.
      For each 10% contribution of dark CO(2) fixation integrated over the entire
      experiment, the delta(13)C content of the tissue was, thus, approximately 1.8 per
      thousand less negative. Extrapolation of the observations to plants previously
      surveyed under natural conditions suggests that the most commonly expressed
      version of CAM in the field, "the typical CAM plant," involves plants that gain
      about 71% to 77% of their carbon by dark fixation, and that the isotopic signals
      of plants that obtain one-third or less of their carbon in the dark may be
      confused with C(3) plants when identified on the basis of carbon isotope content
      alone.

PMID- 12177496
TI  - Induction of mitochondrial alternative oxidase in response to a cell signal
      pathway down-regulating the cytochrome pathway prevents programmed cell death.
AB  - Treatment of tobacco (Nicotiana tabacum L. cv Petit Havana SR1) cells with
      cysteine (Cys) triggers a signal pathway culminating in a large loss of
      mitochondrial cytochrome (cyt) pathway capacity. This down-regulation of the cyt
      path likely requires events outside the mitochondrion and is effectively blocked
      by cantharidin or endothall, indicating that protein dephosphorylation is one
      critical process involved. Generation of reactive oxygen species, cytosolic
      protein synthesis, and Ca(2+) flux from organelles also appear to be involved.
      Accompanying the loss of cyt path is a large induction of alternative oxidase
      (AOX) protein and capacity. Induction of AOX allows the cells to maintain high
      rates of respiration, indicating that the lesion triggered by Cys is in the cyt
      path downstream of ubiquinone. Consistent with this, transgenic (AS8) cells
      unable to induce AOX (due to the presence of an antisense transgene) lose all
      respiratory capacity upon Cys treatment. This initiates in AS8 a programmed cell
      death pathway, as evidenced by the accumulation of oligonucleosomal fragments of
      DNA as the culture dies. Alternatively, wild-type cells remain viable and
      eventually recover their cyt path. Induction of AOX in response to a chemical
      inhibition of the cyt path (by antimycin A) is also dependent upon protein
      dephosphorylation and the generation of reactive oxygen species. Common events
      required for both down-regulation of the cyt path and induction of AOX may
      represent a mechanism to coordinate the biogenesis of these two electron
      transport paths. Such coordinate regulation may be necessary, not only to satisfy
      metabolic demands, but also to modulate the initiation of a programmed cell death
      pathway responsive to mitochondrial respiratory status.

PMID- 12177499
TI  - Mitochondrial alternative oxidase is not a critical component of plant viral
      resistance but may play a role in the hypersensitive response.
AB  - Transgenic tobacco (Nicotiana tabacum) with altered levels of mitochondrial
      alternative oxidase (AOX) were used to examine the potential role of this
      electron transport chain protein in resistance to tobacco mosaic virus. We
      examined the effect of AOX expression on the salicylic acid-induced resistance in
      susceptible plants and the resistance responses of plants harboring the N-gene. A
      lack of AOX did not compromise the ability of salicylic acid treatment to
      heighten the resistance of susceptible plants. In plants with the N-gene, a lack
      of AOX did not compromise the ability of the hypersensitive response to restrict
      the virus or the ability of the plant to develop systemic acquired resistance.
      Overexpression of AOX did not heighten the resistance of susceptible plants, but
      did result in smaller hypersensitive response lesions, suggesting a link between
      mitochondrial function and this programmed cell death event. We conclude that AOX
      is not a critical component of the previously characterized salicylhydroxamic
      acid-sensitive pathway important in viral resistance.

PMID- 12177498
TI  - AtCOX17, an Arabidopsis homolog of the yeast copper chaperone COX17.
AB  - We have identified a new plant gene, AtCOX17, encoding a protein that shares
      sequence similarity to COX17, a Cu-binding protein from yeast (Saccharomyces
      cerevisiae) and vertebrates that mediates the delivery of Cu to the mitochondria
      for the assembly of a functional cytochrome oxidase complex. The newly
      characterized Arabidopsis protein has six Cys residues at positions corresponding
      to those known to coordinate Cu binding in the yeast homolog. Moreover, we show
      that the Arabidopsis COX17 cDNA complements a COX17 mutant of yeast restoring the
      respiratory deficiency associated with that mutation. These two lines of evidence
      indicate that the plant protein identified here is a functional equivalent of
      yeast COX17 and might serve as a Cu delivery protein for the plant mitochondria.
      COX17 was identified by investigating the hypersensitive response-like necrotic
      response provoked in tobacco (Nicotiana tabacum) leaves after harpin inoculation.
      AtCOX17 expression was activated by high concentrations of Cu, bacterial
      inoculation, salicylic acid treatment, and treatments that generated NO and
      hydrogen peroxide. All of the conditions inducing COX17 are known to inhibit
      mitochondrial respiration and to produce an increase of reactive oxygen species,
      suggesting that gene induction occurs in response to stress situations that
      interfere with mitochondrial function.

PMID- 12177500
TI  - Redox regulation of Arabidopsis 3-deoxy-D-arabino-heptulosonate 7-phosphate
      synthase.
AB  - The cDNA for 3-deoxy-D-arabino-heptulosonate 7-phosphate synthase of Arabidopsis
      encodes a polypeptide with an amino-terminal signal sequence for plastid import.
      A cDNA fragment encoding the processed form of the enzyme was expressed in
      Escherichia coli. The resulting protein was purified to electrophoretic
      homogeneity. The enzyme requires Mn(2+) and reduced thioredoxin (TRX) for
      activity. Spinach (Spinacia oleracea) TRX f has an apparent dissociation constant
      for the enzyme of about 0.2 microM. The corresponding constant for TRX m is
      orders of magnitude higher. In the absence of TRX, dithiothreitol partially
      activates the enzyme. Upon alkylation of the enzyme with iodoacetamide, the
      dependence on a reducing agent is lost. These results indicate that the first
      enzyme in the shikimate pathway of Arabidopsis appears to be regulated by the
      ferredoxin/TRX redox control of the chloroplast.

PMID- 12177501
TI  - Cadmium-induced sulfate uptake in maize roots.
AB  - The effect of cadmium (Cd) on high-affinity sulfate transport of maize (Zea mays)
      roots was studied and related to the changes in the levels of sulfate and
      nonprotein thiols during Cd-induced phytochelatin (PC) biosynthesis. Ten
      micromolar CdCl(2) in the nutrient solution induced a 100% increase in sulfate
      uptake by roots. This was not observed either for potassium or phosphate uptake,
      suggesting a specific effect of Cd(2+) on sulfate transport. The higher sulfate
      uptake was not dependent on a change in the proton motive force that energizes
      it. In fact, in Cd-treated plants, the transmembrane electric potential
      difference of root cortical cells was only slightly more negative than in the
      controls, the external pH did not change, and the activity of the plasma membrane
      H(+)-ATPase did not increase. Kinetics analysis showed that in the range of the
      high-affinity sulfate transport systems, 10 to 250 microM, Cd exposure did not
      influence the K(m) value (about 20 microM), whereas it doubled the V(max) value
      with respect to the control. Northern-blot analysis showed that Cd-induced
      sulfate uptake was related to a higher level of mRNA encoding for a putative high
      affinity sulfate transporter in roots. Cd-induced sulfate uptake was associated
      to both a decrease in the contents of sulfate and glutathione and synthesis of a
      large amount of PCs. These results suggest that Cd-induced sulfate uptake depends
      on a pretranslational regulation of the high-affinity sulfate transporter gene
      and that this response is necessary for sustaining the higher sulfur demand
      during PC biosynthesis.

PMID- 12177502
TI  - Two novel mitogen-activated protein signaling components, OsMEK1 and OsMAP1, are
      involved in a moderate low-temperature signaling pathway in rice.
AB  - Rice (Oryza sativa) anther development is easily damaged by moderately low
      temperatures above 12 degrees C. Subtractive screening of cDNA that accumulated
      in 12 degrees C-treated anthers identified a cDNA clone, OsMEK1, encoding a
      protein with features characteristic of a mitogen-activated protein (MAP) kinase
      kinase. The putative OsMEK1 protein shows 92% identity to the maize (Zea mays)
      MEK homolog, ZmMEK1. OsMEK1 transcript levels were induced in rice anthers by 12
      degrees C treatment for 48 h. Similar OsMEK1 induction was observed in shoots and
      roots of seedlings that were treated at 12 degrees C for up to 24 h. It is
      interesting that no induction of OsMEK1 transcripts was observed in 4 degrees C
      treated seedlings. In contrast, rice lip19, encoding a bZIP protein possibly
      involved in low temperature signal transduction, was not induced by 12 degrees C
      treatment but was induced by 4 degrees C treatment. Among the three MAP kinase
      homologs cloned, only OsMAP1 displayed similar 12 degrees C-specific induction
      pattern as OsMEK1. A yeast two-hybrid system revealed that OsMEK1 interacts with
      OsMAP1, but not with OsMAP2 and OsMAP3, suggesting that OsMEK1 and OsMAP1
      probably function in the same signaling pathway. An in-gel assay of protein
      kinase activity revealed that a protein kinase (approximately 43 kD), which
      preferentially uses myelin basic protein as a substrate, was activated by 12
      degrees C treatment but not by 4 degrees C treatment. Taken together, these
      results lead us to conclude that at least two signaling pathways for low
      temperature stress exist in rice, and that a MAP kinase pathway with OsMEK1 and
      OsMAP1 components is possibly involved in the signaling for the higher range low
      temperature stress.

PMID- 12177503
TI  - Inhibition of phospholipase D alpha by N-acylethanolamines.
AB  - N-Acylethanolamines (NAEs) are endogenous lipids in plants produced from the
      phospholipid precursor, N-acylphosphatidylethanolamine, by phospholipase D (PLD).
      Here, we show that seven types of plant NAEs differing in acyl chain length and
      degree of unsaturation were potent inhibitors of the well-characterized, plant
      specific isoform of PLD-PLD alpha. It is notable that PLD alpha, unlike other PLD
      isoforms, has been shown not to catalyze the formation of NAEs from N
      acylphosphatidylethanolamine. In general, inhibition of PLD alpha activity by
      NAEs increased with decreasing acyl chain length and decreasing degree of
      unsaturation, such that N-lauroylethanolamine and N-myristoylethanolamine were
      most potent with IC(50)s at submicromolar concentrations for the recombinant
      castor bean (Ricinus communis) PLD alpha expressed in Escherichia coli and for
      partially purified cabbage (Brassica oleracea) PLD alpha. NAEs did not inhibit
      PLD from Streptomyces chromofuscus, and exhibited only moderate, mixed effects
      for two other recombinant plant PLD isoforms. Consistent with the inhibitory
      biochemical effects on PLD alpha in vitro, N-lauroylethanolamine, but not lauric
      acid, selectively inhibited abscisic acid-induced closure of stomata in epidermal
      peels of tobacco (Nicotiana tabacum cv Xanthi) and Commelina communis at low
      micromolar concentrations. Together, these results provide a new class of
      biochemical inhibitors to assist in the evaluation of PLD alpha physiological
      function(s), and they suggest a novel, lipid mediator role for endogenously
      produced NAEs in plant cells.

PMID- 12177504
TI  - O-methyltransferases involved in the biosynthesis of volatile phenolic
      derivatives in rose petals.
AB  - Rose (Rosa hybrida) flowers produce and emit a diverse array of volatiles,
      characteristic to their unique scent. One of the most prominent compounds in the
      floral volatiles of many rose varieties is the methoxylated phenolic derivative
      3,5-dimethoxytoluene (orcinol dimethyl ether). Cell-free extracts derived from
      developing rose petals displayed O-methyltransferase (OMT) activities toward
      several phenolic substrates, including 3,5-dihydroxytoluene (orcinol), 3
      methoxy,5-hydroxytoluene (orcinol monomethyl ether), 1-methoxy, 2-hydroxy
      benezene (guaiacol), and eugenol. The activity was most prominent in rose cv
      Golden Gate, a variety that produces relatively high levels of orcinol dimethyl
      ether, as compared with rose cv Fragrant Cloud, an otherwise scented variety but
      which emits almost no orcinol dimethyl ether. Using a functional genomics
      approach, we have identified and characterized two closely related cDNAs from a
      rose petal library that each encode a protein capable of methylating the
      penultimate and immediate precursors (orcinol and orcinol monomethyl ether,
      respectively) to give the final orcinol dimethyl ether product. The enzymes,
      designated orcinol OMTs (OOMT1 and OOMT2), are closely related to other plant
      methyltransferases whose substrates range from isoflavones to phenylpropenes. The
      peak in the levels of OOMT1 and OOMT2 transcripts in the flowers coincides with
      peak OMT activity and with the emission of orcinol dimethyl ether.

PMID- 12177505
TI  - Transgenic plant cells lacking mitochondrial alternative oxidase have increased
      susceptibility to mitochondria-dependent and -independent pathways of programmed
      cell death.
AB  - The plant mitochondrial electron transport chain is branched such that electrons
      at ubiquinol can be diverted to oxygen via the alternative oxidase (AOX). This
      pathway does not contribute to ATP synthesis but can dampen the mitochondrial
      generation of reactive oxygen species. Here, we establish that transgenic tobacco
      (Nicotiana tabacum L. cv Petit Havana SR1) cells lacking AOX (AS8 cells) show
      increased susceptibility to three different death-inducing compounds (H(2)O(2),
      salicylic acid [SA], and the protein phosphatase inhibitor cantharidin) in
      comparison with wild-type cells. The timing and extent of AS8 cell death are very
      similar among the three treatments and, in each case, are accompanied by the
      accumulation of oligonucleosomal fragments of DNA, indicative of programmed cell
      death. Death induced by H(2)O(2) or SA occurs by a mitochondria-dependent pathway
      characterized by cytochrome c release from the mitochondrion. Conversely, death
      induced by cantharidin occurs by a pathway without any obvious mitochondrial
      involvement. The ability of AOX to attenuate these death pathways may relate to
      its ability to maintain mitochondrial function after insult with a death-inducing
      compound or may relate to its ability to prevent chronic oxidative stress within
      the mitochondrion. In support of the latter, long-term treatment of AS8 cells
      with an antioxidant compound increased the resistance of AS8 cells to SA- or
      cantharidin-induced death. The results indicate that plants maintain both
      mitochondria-dependent and -independent pathways of programmed cell death and
      that AOX may act as an important mitochondrial "survival protein" against such
      death.

PMID- 12177507
TI  - The two hats of SOS.
AB  - Son of sevenless (SOS) is a guanine nucleotide exchange factor that activates Ras
      in response to growth factor stimulation. SOS also appears to serve as a guanine
      nucleotide exchanger for Rac and, thus, may be involved in cytoskeleton
      reorganization. Nimnual and Bar-Sagi discuss how these two activities of SOS can
      be regulated and how SOS may be recruited to different cellular locations through
      interactions with the adaptor proteins Grb2 and E3b1.

PMID- 12177506
TI  - In vivo interactions between photosynthesis, mitorespiration, and
      chlororespiration in Chlamydomonas reinhardtii.
AB  - Interactions between photosynthesis, mitochondrial respiration (mitorespiration),
      and chlororespiration have been investigated in the green alga Chlamydomonas
      reinhardtii using flash illumination and a bare platinum electrode. Depending on
      the physiological status of algae, flash illumination was found to induce either
      a fast (t(1/2) approximately 300 ms) or slow (t(1/2) approximately 3 s) transient
      inhibition of oxygen uptake. Based on the effects of the mitorespiratory
      inhibitors myxothiazol and salicyl hydroxamic acid (SHAM), and of propyl gallate,
      an inhibitor of the chlororespiratory oxidase, we conclude that the fast
      transient is due to the flash-induced inhibition of chlororespiration and that
      the slow transient is due to the flash-induced inhibition of mitorespiration. By
      measuring blue-green fluorescence changes, related to the redox status of the
      pyridine nucleotide pool, and chlorophyll fluorescence, related to the redox
      status of plastoquinones (PQs) in C. reinhardtii wild type and in a photosystem I
      deficient mutant, we show that interactions between photosynthesis and
      chlororespiration are favored when PQ and pyridine nucleotide pools are reduced,
      whereas interactions between photosynthesis and mitorespiration are favored at
      more oxidized states. We conclude that the plastid oxidase, similar to the
      mitochondrial alternative oxidase, becomes significantly engaged when the PQ pool
      becomes highly reduced, and thereby prevents its over-reduction.

PMID- 12177508
TI  - [Concentration of C-reactive protein, procalcitonin and alpha-1-antitrypsin in
      blood of neonates and infants with signs of inflammation].
AB  - We determined the concentration of C-reactive protein (CRP), procalcilonin (PCT)
      and alpha-1-antitrypsin (AAT) in blood of neonates and infants with suspected
      infection. Investigations were carried out in 88 children. Increased
      concentrations of CRP (>5mg/L). procalcitonin (>0.5ng/ml) and AAT (> 200mg/dl)
      were observed in: CRP - 24%. PCT- 46%, AAT - 49% of neonates in 70, 60 and 70% of
      infants. We concluded, that the examined parameters are good and sensitive
      markers of inflammation in neonates and infants.

PMID- 12177509
TI  - [Neutrophil elastase level in cord blood and diagnosis of infection in mature and
      premature neonates].
AB  - We determined the concentration of umbilical cord blood neutrophil elastase (EN)
      in 143 neonates. The infants were divided into four groups: A - Term non
      infected, B - Term infected, C - Preterm non-infected, D - Preterm infected. In
      the study a low concentration of cord blood elastase in premature children was
      found. It was significantly lower in preterm non-infected (p<0.001) and infected
      (p<0.05) neonates than in non-infected term children. In full-term infected
      neonates mean concentration of elastase was markedly (p<0.001) higher as compared
      to term healthy ones. 87% values of cord blood elastase measured in full-term
      infected neonates and 6% in preterm ones exceed the upper limit reference
      interval (209.3 ug/L) while 97% measurements in preterm neonates (all with and
      without clinical signs of infection) were within the reference range. We conclude
      that significant differences in elastase level in the cord blood depend on age of
      gestation at delivery. These age-dependent differences of elastase concentration
      can be taken into consideration and examination of cord blood elastase
      concentration may provide a valuable indicator in early diagnosis of sepsis in
      neonates. In full-term neonates cord blood neutrophil elastase is a good marker
      of infection.

PMID- 12177510
TI  - [Neonatal erythrodermia - early manifestation of Omenn's syndrome].
AB  - Ommen's syndrome is a rare, autosomal recessive disease that is characterized by
      symptoms of a severe combined immune deficiency, severe infections,
      erythrodermia, hypereosinophilia, hepatosplenomegaly, lymphadenopathy, protracted
      diarrhoea, hypogammaglobulinemia and elevated serum IgE. The presented case
      demonstrates diagnostic problems in recognizing Omenn's syndrome. These resulted
      predominantly from the incomplete clinical picture of the disease in its early
      phase. Persistent erythrodermia was the basic manifestation of the syndrome in
      the initial phase. Since the occurrence of the disease is extremely rare and
      particular symptoms are not pathognomonic, it is their co-occurrence in
      association with typical immunological disorders that enabled to establish the
      diagnosis. Through the presentation of the above case history we should like to
      point to the necessity of considering Omenn's syndrome in differentiating causes
      of erythrodermia in neonates and infants.

PMID- 12177511
TI  - [T-lymphocyte and monocyte activation in the course of infection in children with
      neoplastic disease].
AB  - One of the side effects of antineoplastic treatment is immunosuppression. A
      consequence of this are frequent infections, sometimes with fatal outcome. The
      immunological system "answers" to infections with changes in number and quality
      of cells participating in the inflammatory process. The aim of the study was to
      investigate the subpopulations of mononuclear cells in patients with neoplastic
      (haematologic) diseases during infections. We studied 16 children with acute
      lymphoblastic leukaemia and with lymphomas (Hodgkin and non-Hodgkin). Among our
      patients we note 25 episodes of infections requiring hospitalization. Mean
      percent values of mononuclear antibodies: CD14-PE/CD45-FITC, CD3-FITC/CD19-PE,
      CD4-FITC/CD8-PE, CD3-FITC/CD16+CD56-PE, CD14-PerCP/CD54-PE, CD3-PerCP/CD54RA
      FITC/CD45RO-PE, CD3-PerCP/HLA-DR, CD14-PerCP/HLA-DR. In the examination carried
      out during acute infection, we found higher mean percent values of CD3+ HLDAR+,
      CD14+ CD54+ and CD3+ CD45RO+ cells than in analogous values in the remaining
      examinations. After the infection we found higher percent of CD3
      CD45RA+/CD3+CD45RO+ cells. In a patient with cytomegalovirus pneumonitis our
      examination showed a depression of HLA-DR antigens on monocytes during acute
      infections (10th day of treatment) and return to normal values after 20 days of
      treatment. CONCLUSIONS: (1) The most sensitive expression of infection in
      children with neoplastic disease was the variable percent of HDLA-DR molecules on
      T lymphocytes. (2) Presence of activation indicators on T lymphocytes and
      monocytes can testify that there is persistent function of the immunological
      system in spite of immunosuppression in patients with neoplastic disease. (3)
      Depression in percent value of monocytes with HLA-DR antigens in the course of
      cytomegalovirus pneumonitis confirms its immunosuppressive influence on the human
      organism.

PMID- 12177512
TI  - [Human papilloma virus (HPV) infection in the pathology of the endometrium. Role
      of immunological activation in antiviral and antineoplastic defense].
AB  - Endometrial cancer is one of the most prevalent neoplastic diseases in women, in
      the developed countries. In spite of hormonal dysfunction, no pivotal mechanism
      leading to this pathology is known. The study design was to evaluate the presence
      of human papilloma virus within the endometrium by in situ hybridization and its
      potential role in the occurrence of dysplastic and neoplastic endometrial
      lesions. Immunological antiviral and antitumour defense was investigated by
      cytometric measurement of selected lymphocyte subsets. Viral infection was
      present in nearly 25% of endometrial cancer patients and occasionally within
      endometrial hyperplasia with cellular atypia. The presence of human papilloma
      virus correlated with significant depletion of CD4 lymphocytes as well as
      activated T cells and NK.

PMID- 12177513
TI  - [Hyperhomocysteinaemia in a coeliac disease heterozygote for the two common
      mutations (677C->T and 1298A->C) of the methylenetetrahydrofolate reductase gene.
      Case report].
AB  - A 17 year old girl with coeliac disease was found to have hyperhomocysteinaemia
      (fasting plasma total homocysteine concentration - 19.93 micromol/L; N<12.75
      micromol/L). At the age of 1 5 she gave up gluten-free diet and had only subtle
      signs of chronic malabsorption such as folic acid and iron deficiency. The
      patient was heterozygote for both common mutations (677C->T and J298A->C) of the
      methylenetetrahydrofolate reductase gene. On gluten diet an intake of 5 mg folic
      acid/d from supplements for two weeks resulted in an increase in serum folate and
      a reduction in homocysteine concentration (13.20 micromol/L). The patient
      continued to consume a gluten containing diet and 0.5mg folic acid/d from
      supplements for 4 months and homocysteiene decreased to 12.1 mmol/L.
      Hyperhomocysteinaemia - a cardiovascular and obstetrical risk factor - might be a
      significant problem for patients with celiac disease on gluten-containing diet.

PMID- 12177514
TI  - [Microwave thermography in the assessment of breast pathology].
AB  - Searching for a noninvasive method of the diagnosis of breast pathology was the
      initial reason of setting up this study. The aim of this work was to answer the
      following questions: does the microwave thermography allow us to detect
      pathological masses within the breast and may it be used as the screening test
      taking under consideration its diagnostic accuracy. The results of microwave
      thermography were compared with physical examination, ultrasonomammography,
      mammography, cytology (from aspirating biopsy - BAC) or histopathological
      examination (performed during operation or as open diagnostic biopsy).
      Statistically significant differences in temperatures obtained by thermography,
      were revealed between three groups (healthy control, women with benign breast
      disease and group of patients with breast cancer), for the temperature amplitude
      within whole breast tissue. Statistical significance was also obtained comparing
      temperature amplitude examined beyond palpable breast mass. There was no
      statistical significant differences between tumour volume, clinical stage of
      disease, morphological differentiation of breast disorders and examined
      differences of the values of temperature amplitude. The usefulness of microwave
      thermography in the detection of breast disorders (both breast carcinoma and
      benign breast masses), gives hope for final success in searching for noninvasive
      diagnostic procedures, which can be implemented as a screening examination of
      women population.

PMID- 12177515
TI  - [Postpartum evaluation of amylin secretion in gestational diabetes mellitus].
AB  - Amylin (Islet Amyloid Pancreatic Polypeptide - IAPP) is a hormone cosecreted with
      insulin by pancreatic beta cells in a pulsatile pattern. Recent reports point to
      its essential part in glucose homeostasis. Postpartum evaluation of IAPP release
      in Gestational Diabetes Mellitus (GDM) patients was performed. Our data were
      compared to insulin and peptide-C secretion patterns. We were not able to
      demonstrate a dynamic increase of IAPP in response to glucagon stimuli. However,
      related to GDM, puerperal IAPP levels were significantly higher than in normal
      controls. Lack of postpartum amylin response to glucagon stimulation might be
      interpreted as a primary result of previously reported increases in circulatory
      levels of IAPP during pregnancy complicated by GDM. Post partum elevated IAPP may
      be a useful marker to identify patients with high risk of type 2 diabetes
      mellitus.

PMID- 12177516
TI  - Statistical methods for microarray assays.
AB  - The paper shortly reviews statistical methods used in the area of DNA microarray
      studies. All stages of the experiment are taken into account: planning, data
      collection, data preprocessing, analysis and validation. Among the methods of
      data analysis, the algorithms for estimating differential expression,
      multivariate approaches, clustering methods, as well as classification and
      discrimination are reviewed. The need is stressed for routine statistical data
      processing protocols and for the search of links of microarray data analysis with
      quantitative genetic models.

PMID- 12177517
TI  - Production and morphology of the hybrids Aegilops kotschyi x Secale cereale and
      Ae. biuncialis x S. cereale.
AB  - Hybrids between Aegilops kotschyi and Ae. biuncialis with Secale cereale were
      synthesized. Five Ae. kotschyi and four Ae. biuncialis accessions, as well as one
      inbred and four self-compatible forms of Secale cereale were used for crossing.
      The hybrids were produced directly from cultured embryos or through embryo callus
      culture. Sixty hybrids, 11 involving Ae. kotschyi and 49 Ae. biuncialis, had a
      stable somatic chromosome number 2n = 3x = 21. The plants showed good vegetative
      vigour and tillering capacity. Morphologically the hybrids were intermediate
      between their parents and completely sterile. In vitro propagation of Ae.
      kotschyi and Ae. biuncialis x S. cereale hybrids revealed that their capacity for
      callus production and plantlet regeneration - varies.

PMID- 12177518
TI  - Influence of anther pretreatment on the efficiency of androgenesis in barley.
AB  - The change in the developmental pathway of microspores from gametophytic to
      sporophytic is induced by stress during pretreatment of spikes and anthers. In
      our experiments, anther culture of three barley cultivars was tested with regard
      to the effect of chilling at 4 degrees C for 28 days, starvation in 0.3 M
      mannitol solution for 4 days, and a combination of both methods. Chilling was
      shown to increase embryo/callus formation, while mannitol treatment favoured
      plant development, including development of green plants; simultaneous
      application of the two stress factors for 4 days proved to be ineffective. The
      tested cultivars exhibited a similar ability (calculated per 100 transferred
      embryos/calli) to develop plants without pretreatment; however, their responses
      to stress varied greatly. The collected data indicate that mannitol pretreatment,
      as compared to chilling, is more efficient in responsive cultivars.

PMID- 12177519
TI  - Putative resistance genes of cereals: structure and expected function.
AB  - Sequences of two recently cloned genes playing a role in resistance against wheat
      pathogens (receptor-like kinase Lrk10 and Cre3 genes) were used to search for
      similarity of cereal clones included in the NCBI database. We found 23 clones
      with similarity to the Cre3 gene with predicted NBS and LRR domains, and 50
      clones with serine/threonine kinase function and similarity to the new receptor
      like kinase gene Lrk10 from wheat. In those two groups of clones some
      conservative nucleotide sequences were identified. Two sequences are identical
      between the majority of resistance gene candidate clones with a high similarity
      to Lrk10, and two sequences are identical between the majority of resistance gene
      candidate clones with similarity to the Cre3 gene.

PMID- 12177520
TI  - Novel linkage mapping approach using DNA pooling in human and animal genetics.
      II. Detection of quantitative traits loci in dairy cattle.
AB  - Selective DNA pooling is an advanced methodology for linkage mapping of
      quantitative trait loci (QTL) in farm animals. The principle is based on
      densitometric estimates of marker allele frequency in pooled DNA samples of
      phenotypically extreme individuals from half-sib, backcross and F(2) experimental
      designs in farm animals. This methodology provides a rapid and efficient analysis
      of a large number of individuals with short tandem repeat markers that are
      essential to detect QTL through the genome - wide searching approach. Several
      strategies involving whole genome scanning with a high statistical power have
      been developed for systematic search to detect the quantitative traits loci and
      linked loci of complex traits. In recent studies, greater success has been
      achieved in mapping several QTLs in Israel-Holstein cattle using selective DNA
      pooling. This paper outlines the currently emerged novel strategies of linkage
      mapping to identify QTL based on selective DNA pooling with more emphasis on its
      theoretical pre-requisite to detect linked QTLs, applications, a general theory
      for experimental half-sib designs, the power of statistics and its feasibility to
      identify genetic markers linked QTL in dairy cattle. The study reveals that the
      application of selective DNA pooling in dairy cattle can be best exploited in the
      genome-wide detection of linked loci with small and large QTL effects and applied
      to a moderately sized half-sib family of about 500 animals.

PMID- 12177521
TI  - Relationship between microsatellite marker alleles on chromosomes 1-5 originating
      from the Rhode Island Red and Green-legged Partrigenous breeds and egg production
      and quality traits in F(2) mapping population.
AB  - The objective of this study was to determine the relationship between the origin
      of marker alleles from the Rhode Island Red (RIR) and Green-legged Partrigenous
      (GlP) breeds and chosen egg production and quality traits in F(2) generation
      consisting of 10 full-sib families. Polymorphism analysis of 23 microsatellite
      markers within the mapping population (519 F(2)) was made. In parental generation
      17 alleles were identified as specific for the GlP and 23 for the RIR. The least
      squares method was used to evaluate the significance of effects of genotype
      (GlP/GlP, RIR/RIR, GlP/RIR) on the analysed quantitative traits. Thirty traits of
      egg production and quality were measured during the laying period. It was shown
      that the effects of the genotype (GlP/GlP, RIR/RIR, GlP/RIR) at the loci on
      analysed traits of F(2) animals were diversified. Significant effects were found
      for 16 traits. These results confirm that the analysed microsatellite loci may be
      linked to the genes affecting egg production and quality traits. The loci
      examined and the experimental population constitutes a valuable material for QTL
      mapping (linkage analysis).

PMID- 12177522
TI  - Simultaneous identification of ryanodine receptor 1 (RYR1) and estrogen receptor
      (ESR) genotypes with the multiplex PCR-RFLP method in Polish Large White and
      Polish Landrace pigs.
AB  - A method allowing simultaneous genotyping of two loci: ryanodine receptor 1
      (RYR1) and estrogen receptor (ESR) is presented. In multiplex PCR amplification,
      two amplicons were simultaneously produced: a 272 bp fragment of RYR1 gene and a
      185 bp fragment of ESR gene and were then subjected to "one-tube" restriction
      enzyme digestion with Hin6 I and Ava I, respectively. A total of 122 Polish Large
      White and Polish Landrace pigs were genotyped by this method, demonstrating its
      reliability, convenience and lower costs. This method may be useful in the wide
      scale genotyping of both loci in pig breeding programmes.

PMID- 12177523
TI  - Reproductive performance of a transgenic boar carrying the bovine growth hormone
      gene (bGH).
AB  - The aim of this study was to obtain information on the possible influence of the
      bovine growth hormone gene (bGH) on gametogenesis and reproductive parameters of
      a 2-year-old Polish Landrace transgenic boar. The bGH gene construct had been
      introduced into the zygote of the boar with the use of the microinjection
      technique. On the basis of the available documentation we established that the
      fertility of the investigated transgenic (bGH) boar was low in comparison with
      other animals of the Polish Landrace breed, with a poor libido, ineffective
      matings and, on average, 3 live piglets less per litter. Samples of testis tissue
      from the boar were obtained after castration. In total, we observed 100
      spermatocytes and all of them had normally paired bivalents. It is possible that
      the boar's lower fertility was caused by some, as yet unknown factor.

PMID- 12177524
TI  - Genetic basis of neural tube defects. I. Regulatory genes for the neurulation
      process.
AB  - Neural tube defects (NTD) together with cardiovascular system defects are the
      most common malformations in the Polish population (2.05-2.68/1000 newborns).
      They arise during early embryogenesis and are caused by an improper neural groove
      closure during the neurulation process. NTD can arise from the influence of
      specific environmental factors on the foetus. The genetic factor is also very
      important, because NTDs have multigenetic conditioning. It was suggested that
      genes connected with the regulation of neurulation could also be involved in NTD
      aetiology, especially when their deletion or modification leads to neural tube
      defects in the mouse model. Examples are genes from the PAX family, T
      (Brachyury), BRCA1 and PDGFRA genes.

PMID- 12177525
TI  - Documenting ancient DNA quality via alpha satellite amplification and assessment
      of clone sequence diversity.
AB  - C/G-->T/A nucleotide alterations have been shown to hamper the straightforward
      interpretation of mitochondrial DNA sequence data derived from ancient tissues.
      Attempting to characterise this finding with respect to nuclear DNA, we
      contrasted two established protocols: (i) an enzymatic repair of damaged DNA,
      thereby translating and closing nicks in the DNA, and (ii) the application of N
      phenacylthiazolium bromide, which cleaves glucose-derived protein crosslinks,
      presumably derived from Maillard reactions. We used medieval human bones that
      were refractory to standard PCR procedures. Due to negligible presence of short
      tandem repeat loci and also mitochondrial sequences, the extracted ancient DNA
      needed a higher copy PCR system to yield amplification products. The chosen PCR
      target was specific alphoid repetitive DNA with an experimentally determined
      minimum of 1000 copies per haploid genome. Alphoid repeat segments were generated
      from both contemporary DNA and DNA extracts of two human skeletons dating from
      450-600 AD (omitting uracil N-glycosylase pre-treatment of the extracted
      samples), and were subsequently cloned and sequenced. The sequences were
      evaluated for the number and type of nucleotide alterations noted after the
      different pre-treatments, and were compared to our alphoid consensus sequence
      generated from modern DNA. Both methods failed to reflect the expected 32%
      variability among single alphoid repeats (accounting for locus-specific
      differences and polymerase errors) as well as to display the actual 2.88 ratio of
      transitions to transversions. Our data obtained from high-copy-number nuclear DNA
      mirror the phenomenon of sequence deviations observed in mitochondrial DNA
      extracted from old specimens.

PMID- 12177526
TI  - Direct sequencing of PCR products for mutation detection in osteogenesis
      imperfecta.
AB  - This work present a short and simple method for mutation detection in type I
      collagen genes, based on the direct sequencing of single-stranded DNA. The
      sequencing of type I collagen genes is complicated and difficult because of their
      large size and highly repetitive and GC-rich coding regions. Although many
      techniques have been developed for mutation screening in osteogenesis imperfecta
      (OI), they represent different degrees of sensitivity and are difficult to
      reproduce and too expensive for application in each laboratory. The method
      described here is short, easy and especially useful for sequencing of collagen
      genes in OI cases, in which the region with a suspected structural defect is
      localized by collagen analysis.

PMID- 12177527
TI  - Differences between rats and mice in induction of 4S beta-naphthoflavone-binding
      protein expression by treatment with beta-naphthoflavone.
AB  - Sprague-Dawley rats and several inbred strains of mice were compared with respect
      to the induction of 4S BNF-binding protein expression by treatment with beta
      naphthoflavone (BNF), an aryl hydrocarbon receptor (AhR) ligand. Inbred strains
      of mice chosen for the study encompassed 3 allelic forms of AhR found in Mus
      musculus so far. As it was reported by us earlier, treating rats with BNF caused
      a significant induction of BNF-binding protein expression. By contrast, no BNF
      binding protein was detected in mice treated with BNF in corn oil as a vehicle or
      with corn oil itself.

PMID- 12177528
TI  - Induction of light emission by luminescent bacteria treated with UV light and
      chemical mutagens.
AB  - Intensity of light emission by luminescent bacteria in response to UV irradiation
      and chemical mutagens was tested. We demonstrated that luminescence of six
      strains of marine bacteria (belonging to four species: Photobacterium leiognathi,
      P. phosphoreum, Vibrio fischeri and V. harveyi) is significantly increased by UV
      irradiation relatively shortly after dilution of cultures. Such a stimulation of
      luminescence was abolished in cells treated with chloramphenicol 15 min before UV
      irradiation, indicating that effective gene expression is necessary for UV
      mediated induction of light emission. These results suggest that stimulation of
      luminescence in UV-irradiated bacterial cells may operate independently of the
      quorum sensing regulation. A significant induction of luminescence was also
      observed upon treatment of diluted cultures of all investigated strains with
      chemical mutagens: sodium azide (SA), 2-methoxy-6-chloro-9-(3-(2
      chloroethyl)aminopropylamino)acridine x 2HCl (ICR-191), 4-nitro-o
      phenylenediamine (NPD), 4-nitroquinolone-N-oxide (NQNO), 2-aminofluorene (2-AF),
      and benzo[alpha]pyrene. These results support the proposal that genes involved in
      bioluminescence belong to the SOS regulon. The use of bacterial luminescence
      systems in assays for detection of mutagenic compounds is discussed in the light
      of this proposal.

PMID- 12177529
TI  - Monte Carlo simulation of genome viability with paralog replacement.
AB  - Recent analyses of genome content have revealed that many single functions, even
      in haploid organisms, can be executed by more than one gene. As a result,
      experimental disruption of many individual genes does not exert lethal effects on
      the organism or even any visible change in the phenotype of the organism with a
      knockedout gene. Our analysis shows that such genetic redundancy allows for an
      appreciably higher mutation load in the genome simulations before the viability
      of the whole organism is destroyed.

PMID- 12177530
TI  - Operationalizing biodiversity for conservation planning.
AB  - Biodiversity has acquired such a general meaning that people now find it
      difficult to pin down a precise sense for planning and policy-making aimed at
      biodiversity conservation. Because biodiversity is rooted in place, the task of
      conserving biodiversity should target places for conservation action; and because
      all places contain biodiversity, but not all places can be targeted for action,
      places have to be prioritized. What is needed for this is a measure of the extent
      to which biodiversity varies from place to place. We do not need a precise
      measure of biodiversity to prioritize places. Relative estimates of similarity or
      difference can be derived using partial measures, or what have come to be called
      biodiversity surrogates. Biodiversity surrogates are supposed to stand in for
      general biodiversity in planning applications. We distinguish between true
      surrogates, those that might truly stand in for general biodiversity, and
      estimator surrogates, which have true surrogates as their target variable. For
      example, species richness has traditionally been the estimator surrogate for the
      true surrogate, species diversity. But species richness does not capture the
      differences in composition between places; the essence of biodiversity. Another
      measure, called complementarity, explicitly captures the differences between
      places as we iterate the process of place prioritization, starting with an
      initial place. The relative concept of biodiversity built into the definition of
      complementarity has the level of precision needed to undertake conservation
      planning.

PMID- 12177531
TI  - Representing biodiversity: data and procedures for identifying priority areas for
      conservation.
AB  - Biodiversity priority areas together should represent the biodiversity of the
      region they are situated in. To achieve this, biodiversity has to be measured,
      biodiversity goals have to be set and methods for implementing those goals have
      to be applied. Each of these steps is discussed. Because it is impossible to
      measure all of biodiversity, biodiversity surrogates have to be used. Examples
      are taxa sub-sets, species assemblages and environmental domains. Each of these
      has different strengths and weaknesses, which are described and evaluated. In
      real-world priority setting, some combination of these is usually employed. While
      a desirable goal might be to sample all of biodiversity from genotypes to
      ecosystems, an achievable goal is to represent, at some agreed level, each of the
      biodiversity features chosen as surrogates. Explicit systematic procedures for
      implementing such a goal are described. These procedures use complementarity, a
      measure of the contribution each area in a region makes to the conservation goal,
      to estimate irreplaceability and flexibility, measures of the extent to which
      areas can be substituted for one another in order to take competing land uses
      into account. Persistence and vulnerability, which also play an important role in
      the priority setting process, are discussed briefly.

PMID- 12177532
TI  - Data requirements and data sources for biodiversity priority area selection.
AB  - The data needed to prioritize areas for biodiversity protection are records of
      biodiversity features - species, species assemblages, environmental classes - for
      each candidate area. Prioritizing areas means comparing candidate areas, so the
      data used to make such comparisons should be comparable in quality and quantity.
      Potential sources of suitable data include museums, herbariums and natural
      resource management agencies. Issues of data precision, accuracy and sampling
      bias in data sets from such sources are discussed and methods for treating data
      to minimize bias are reviewed.

PMID- 12177533
TI  - Place prioritization for biodiversity content.
AB  - The prioritization of places on the basis of biodiversity content is part of any
      systematic biodiversity conservation planning process. The place prioritization
      procedure implemented in the ResNet software package is described. This procedure
      is primarily based on the principles of rarity and complementarity. Application
      of the procedure is demonstrated with two analyses, one data set consisting of
      the distributions of termite genera in Namibia, and the other consisting of the
      distributions of bird species in the Islas Malvinas/Falkland Islands. The
      attributes that data sets should have for the effective and reliable application
      of such procedures are discussed. The procedure used here is compared to some
      others that are also currently in use.

PMID- 12177534
TI  - Birds as surrogates for biodiversity: an analysis of a data set from southern
      Quebec.
AB  - Surrogacy analysis consists of determining a set of biotic or environmental
      parameters which can be rapidly assessed in the field and reliably used to
      prioritize places for biodiversity conservation. Whether adequate surrogate sets
      exist remains an open and relatively unexplored question though its solution is
      central to the aims of conservation biology. This paper analyses the surrogacy
      problem by prioritizing places using surrogate lists and comparing these results
      with those obtained by using more comprehensive species lists. More specifically,
      it explores (i) the possibility of using bird distributions, which are often
      easily available, as surrogates for species at risk (endangered and threatened
      species), which are presumed to be an important component of biodiversity; and
      (ii) the methodological question of how spatial scale influences surrogate
      success. The data set analysed, from southern Quebec, is one of the most complete
      biotic data sets available at the regional scale. Contrary to some previous
      analyses, the results obtained suggest that the surrogacy problem is potentially
      solvable.

PMID- 12177536
TI  - Bet-hedging applications for conservation.
AB  - One of the early tenets of conservation biology is that population viability is
      enhanced by maintaining multiple populations of a species. The strength of this
      tenet is justified by principles of bet-hedging. Management strategies that
      reduce variance in population size will also reduce risk of extinction.
      Asynchrony in population fluctuations in independent populations reduces variance
      in the aggregate of populations whereas environmental correlation among areas
      increases the risk that all populations will go extinct. We review the
      theoretical rationale of bet-hedging and suggest applications for conservation
      management of least terns in Nebraska and grizzly bears in the northern Rocky
      Mountains of the United States. The risk of extinction for least terns will be
      reduced if we can sustain the small central Platte River population in addition
      to the larger population on the lower Platte. Similarly, by restoring grizzly
      bears to the Bitterroot wilderness of Idaho and Montana can reduce the
      probability of extinction for grizzly bears in the Rocky Mountains of the United
      States by as much as 69-93%.

PMID- 12177535
TI  - Persistence and vulnerability: retaining biodiversity in the landscape and in
      protected areas.
AB  - An objective of biodiversity conservation activities is to minimize the exposure
      of biodiversity features to threatening processes and to ensure, as far as
      possible, that biodiversity persists in the landscape. We discuss how issues of
      vulnerability and persistence can and should be addressed at all stages of the
      conservation planning and implementation process. Procedures for estimating the
      likelihood of persistence and for measuring degrees of vulnerability at different
      spatial and temporal scales using subjective assessments, rules of thumb and
      analytical and simulation models are reviewed. The application of information on
      vulnerability and persistence to conservation planning and management is
      discussed under the headings of natural dynamics, replication of protection,
      levels of representation, source and sink population structures, refuges and
      critical resources, reserve design, habitat fragmentation and levels of
      management.

PMID- 12177538
TI  - Choosing appropriate temporal and spatial scales for ecological restoration.
AB  - Classic ecological restoration seems tacitly to have taken the Clementsian
      "balance of nature" paradigm for granted: plant succession terminates in a climax
      community which remains at equilibrium until exogenously disturbed after which
      the process of succession is restarted until the climax is reached. Human
      disturbance is regarded as unnatural and to have commenced in the Western
      Hemisphere at the time of European incursion. Classic ecological restoration thus
      has a clear and unambiguous target and may be conceived as aiming to foreshorten
      the natural processes that would eventually lead to the climax of a given site,
      which may be determined by its state at "settlement". According to the new "flux
      of nature" paradigm in ecology a given site has no telos and is constantly
      changing. Human disturbance is ubiquitous and long-standing, and at certain
      spatial and temporal scales is "incorporated". Any moment in the past 10,000
      years that may be selected as a benchmark for restoration efforts thus appears to
      be arbitrary. Two prominent conservationists have therefore suggested that the
      ecological conditions in North America at the Pleistocene-Holocene boundary,
      prior to the anthropogenic extinction of the Pleistocene megafauna, be the target
      for ecological restoration. That suggestion explicitly assumes evolutionary
      temporal scales and continental spatial scales as the appropriate frame of
      reference for ecological restoration. However, ecological restoration should be
      framed in ecological spatio-temporal scales, which may be defined temporally in
      reference to ecological processes such as disturbance regimes and spatially in
      reference to ecological units such as landscapes, ecosystems, and biological
      provinces. Ecological spatio-temporal scales are also useful in achieving a
      scientifically defensible distinction between native and exotic species, which
      plays so central a role in the practice of ecological restoration and the
      conservation of biodiversity. Because post-settlement human disturbances have
      exceeded the limits of such scales, settlement conditions can be justified
      scientifically as appropriate targets of restoration efforts without recourse to
      obsolete teleological concepts of equilibria and without ignoring the presence
      and ecological influence of indigenous peoples.

PMID- 12177537
TI  - The role of trade-offs in biodiversity conservation planning: linking local
      management, regional planning and global conservation efforts.
AB  - Biodiversity conservation planning requires trade-offs, given the realities of
      limited resources and the competing demands of society. If net benefits for
      society are important, biodiversity assessment cannot occur without other
      sectoral factors "on the table". In trade-offs approaches, the biodiversity value
      of a given area is expressed in terms of the species or other components of
      biodiversity that it has that are additional to the components protected
      elsewhere. That "marginal gain" is called the complementarity value of the area.
      A recent whole-country planning study for Papua New Guinea illustrates the
      importance of complementarity-based trade-offs in determining priority areas for
      biodiversity conservation, and for designing economic instruments such as
      biodiversity levies and offsets. Two international biodiversity programs provide
      important new opportunities for biodiversity trade-offs taking complementarity
      into account. Both the Millennium Ecosystem Assessment and the Critical
      Ecosystems or "hotspots" programs can benefit from an explicit framework that
      incorporates trade-offs, in which a balance is achieved not only by land-use
      allocation among areas, but also by the crediting of partial protection of
      biodiversity provided by sympathetic management within areas. For both
      international programs, our trade-offs framework can provide a natural linkage
      between local, regional and global planning levels.

PMID- 12177539
TI  - The principle of complementarity in the design of reserve networks to conserve
      biodiversity: a preliminary history.
AB  - Explicit, quantitative procedures for identifying biodiversity priority areas are
      replacing the often ad hoc procedures used in the past to design networks of
      reserves to conserve biodiversity. This change facilitates more informed choices
      by policy makers, and thereby makes possible greater satisfaction of conservation
      goals with increased efficiency. A key feature of these procedures is the use of
      the principle of complementarity, which ensures that areas chosen for inclusion
      in a reserve network complement those already selected. This paper sketches the
      historical development of the principle of complementarity and its applications
      in practical policy decisions. In the first section a brief account is given of
      the circumstances out of which concerns for more explicit systematic methods for
      the assessment of the conservation value of different areas arose. The second
      section details the emergence of the principle of complementarity in four
      independent contexts. The third section consists of case studies of the use of
      the principle of complementarity to make practical policy decisions in
      Australasia, Africa, and America. In the last section, an assessment is made of
      the extent to which the principle of complementarity transformed the practice of
      conservation biology by introducing new standards of rigor and explicitness.

PMID- 12177540
TI  - Epidural injections for the treatment of symptomatic lumbar herniated discs.
AB  - Epidural steroid injections are widely used as part of the conservative care for
      symptomatic herniated lumbar discs. There are studies showing their
      effectiveness, and some studies demonstrating no clinical benefits. The purpose
      of this study was to evaluate the effectiveness of epidural steroid injections
      for patients with symptomatic lumbar disc herniations who were surgical
      candidates. Sixty-nine patients were diagnosed with a herniated disc in the
      lumbar spine and remained symptomatic despite conservative care, and were treated
      with an epidural injection in an attempt to avoid surgical discectomy. Of the
      total group of 69 patients (average age = 44.8 years, range 19-77 years, average
      follow-up = 1.5 years), 53 (77%) had successful resolution or significant
      decrease of their symptoms and were able to avoid surgery. Only 16 (23%) patients
      failed to have significant relief of their symptoms and required surgical
      treatment of their herniated disc. Epidural steroid injections have a reasonable
      success rate for the alleviation of radicular symptoms from lumbar herniated
      discs for up to twelve to twenty-seven months. Patients treated with injections
      may be able to avoid surgical treatment up to this period and perhaps even
      longer.

PMID- 12177541
TI  - Local application of steroids following lumbar discectomy.
AB  - In this prospective randomized clinical study, the effectiveness of epidural
      steroids to reduce pain following lumbar disc surgery was assessed. Sixty-one
      patients undergoing lumbar discectomy were included. They were assigned randomly
      to receive, immediately after removal of the disc, either 80 mg
      methylprednisolone acetate (Depomedrol) or the same amount (2 mL) of saline. Both
      were soaked in 2.5 x 2.5 cm of collagen absorbable hemostat (Instat) that was
      left on the decompressed nerve root. All discs were removed in the same way via
      unilateral flavectomy. The patients were asked to grade the pain intensity daily
      in the first 2 weeks and 1 year after surgery. Pain intensity was evaluated by
      the visual analog scale from 0 to 10, zero being no pain and 10 being the most
      severe pain. Statistically significant back pain relief was observed on
      postoperative days 1, 2, 6, and 14 in the study group (the group that received
      steroids). No difference between the two groups was found 1 year after surgery or
      when leg pain was compared. No side effects that could be related to the steroids
      were observed.

PMID- 12177542
TI  - Preoperative instability does not influence the clinical outcome in patients with
      cervical spondylotic myelopathy treated with expansive laminoplasty.
AB  - Sixty-seven patients with cervical spondylotic myelopathy treated with expansive
      laminoplasty were retrospectively reviewed at a minimum 2-year follow-up. This
      study was designed to evaluate whether preoperative instability influences the
      clinical outcome in patients with cervical spondylotic myelopathy treated with
      laminoplasty without spinal fusion. Patients with preoperative instability were
      older and had shorter durations of symptoms prior to surgery than those without
      the instability. There were no significant differences in prevalence of axial
      symptoms, neurologic recovery, or radiologic findings between patients with and
      without preoperative cervical instability. At follow-up, the cervical range of
      motion was limited to 43.5% of the preoperative range, and no cervical
      instability was observed in any patients. Preoperative instability does not
      influence the clinical outcome and can be ignored if expansive laminoplasty is
      indicated for patients with cervical spondylotic myelopathy.

PMID- 12177543
TI  - Combined anterior and posterior approach for managing basilar invagination
      associated with type I Chiari malformation.
AB  - Ventral brainstem compression is common in patients with basilar invagination
      associated with type I Chiari malformation. The aim of this study was to
      investigate the reliability of a combined one-session anterior-posterior surgical
      approach for these patients. Nine patients underwent transoral odontoidectomy,
      posterior foramen magnum decompression, occipitocervical fixation, and bone
      grafting. All but two patients had ventral and dorsal operations in one surgical
      sitting. One of these two individuals had previously undergone posterior
      decompressive surgery at another hospital, but his condition had deteriorated
      rapidly afterward. The mean follow-up time was 19 months (range, 14-30 months).
      There was no mortality and no significant morbidity in this series. All but one
      of the patients showed significant improvement in their symptoms. Chiari
      malformations have a surprisingly high association with basilar invagination, and
      patients may have symptoms in both conditions. If there is a marked anterior
      compression, anterior transoral and posterior decompression, fusion, and
      instrumentation is an optimal strategy for treating patients with basilar
      invagination associated with type I Chiari malformation.

PMID- 12177544
TI  - Change of barometric pressure influences low back pain in patients with vacuum
      phenomenon within lumbar intervertebral disc.
AB  - The present study investigates whether changes in barometric pressure influence
      low back pain in patients with vacuum phenomenon within lumbar intervertebral
      discs. Twenty-four patients with low back pain were examined: 12 with vacuum
      phenomenon within the intervertebral discs (VP [+] group) and 12 without the
      vacuum phenomenon (VP [-] group). All patients consented to an evaluation of low
      back pain in a hyperbaric oxygen chamber. In the VP (+) group, low back pain
      became more severe in one patient when atmospheric pressure was elevated, and in
      eight patients when atmospheric pressure was decreased. In the VP (-) group, two
      patients experienced more severe low back pain when atmospheric pressure was
      decreased. Our study demonstrated that low back pain might be aggravated by
      atmosphere depression in patients with lumbar disease associated with the vacuum
      phenomenon.

PMID- 12177545
TI  - Pro-inflammatory and anti-inflammatory cytokine increases after spinal
      instrumentation surgery.
AB  - We investigated the effects of instrumentation on postoperative inflammatory
      reaction and identified standard changes in serum cytokine concentrations after
      spinal surgery. Pro-inflammatory cytokines [interleukin (IL)-6 and IL-8] and anti
      inflammatory cytokines [IL-10, IL-1 receptor antagonist (ra), and soluble tumor
      necrosis factor receptors (sTNF-R) I and II] were assayed in serum from seven
      patients with lumbar spinal posterior decompression, six with spinal
      decompression and posterolateral fusion without instrumentation and seven with
      spinal decompression and posterolateral fusion with instrumentation. All
      cytokines after spinal instrumentation increased significantly more than in other
      groups on postoperative days 0 and 1. Seven days after SI, IL-6, -8, and -10 had
      normalized, but IL-1ra and sTNF-RI and sTNF-RII remained elevated. Both pro
      inflammatory and anti-inflammatory cytokines were enhanced by implants in the
      acute phase, whereas only anti-inflammatory cytokines were enhanced by
      instruments in the subacute phase.

PMID- 12177546
TI  - Outcomes in surgical treatment of "idiopathic-like" scoliosis associated with
      syringomyelia.
AB  - Patients with "idiopathic-like" spinal deformities associated with syringomyelia
      were retrospectively reviewed. Ten patients had surgical stabilization of their
      curvatures with at least a 2-year follow-up, and an additional five patients were
      evaluated for deformity pattern with <2 years of follow-up. Paralytic curve
      patterns, scoliosis associated with spina bifida, congenital scoliosis, or other
      associated syndromes were discarded. All 10 patients with surgery who were
      followed for an average of 46 months lost 10 degrees correction above, through,
      or below the instrumented segments. A total of 50% lost correction through the
      instrumented segments. Anterior fusion stabilized the instrumented portion of the
      spine better than posterior instrumentation alone. Eighty percent of the 15
      patients had thoracic kyphosis >40 degrees. Only one patient was lordoscoliotic.
      Syringomyelia deformities tend to be kyphoscoliotic in 80% of cases and behave
      more like paralytic curvatures postoperatively. MRI is recommended for apparent
      idiopathic scoliotic curvatures that are kyphoscoliotic and not lordoscoliotic.

PMID- 12177547
TI  - Active range of motion utilized in the cervical spine to perform daily functional
      tasks.
AB  - This was a descriptive study to examine active range of motion required in the
      cervical spine during functional tasks of daily living. The objective of this
      study was to determine the mean active range of motion of the cervical spine
      required to perform 13 daily functional tasks. Previous research has examined the
      absolute ranges of cervical motion for women and men 20-60 years of age; however,
      no previous study has determined the amount and type of motion that is required
      for routine activities of daily living. Twenty-eight college-aged students (n =
      28) served as healthy subjects and performed three trials of 13 daily tasks of
      functional activity. The subject's starting position and end range of motion for
      flexion-extension, rotation, and side bending of each task were observed and
      recorded using the cervical range of motion device. The three trials were
      averaged, and ranges of motion across the 28 subjects were reported. Of the 13
      daily functional tasks performed, tying shoes (flexion-extension 66.7 degrees),
      backing up a car (rotation 67.6 degrees), washing hair in the shower (flexion
      extension 42.9 degrees), and crossing the street (rotation head left 31.7 degrees
      and rotation head right 54.3 degrees) required the greatest full active range of
      motion of the cervical spine. Flexion-extension and rotation of the cervical
      spine are important to enable functional activity. Four of the 13 daily tasks
      performed required 30-50% of active range of motion. Side bending was seen to be
      coupled with rotation in completion of tasks. This article provides a baseline of
      normal motion of the neck required for activities of daily living and can be used
      in the assessment of disease states and disability.

PMID- 12177548
TI  - Posture-dependent isometric trunk extension and flexion strength in normal male
      and female subjects.
AB  - The objective of this study was to quantify the relationship between trunk
      posture and trunk muscle function in a group of young, normal male and female
      subjects. Ten male and 10 female subjects performed isometric flexion and
      extension tasks using a trunk dynamometer. Peak isometric torque was recorded in
      flexion and extension at 10 degrees increments over a sagittal posture range of 
      20 degrees extension to +50 degrees of flexion. Significant differences in trunk
      strength (isometric torque) were found between males and females, at various
      sagittal plane trunk postures, and between flexion (F) and extension (E) tasks.
      Flexion torque was greatest at 20 degrees to 30 degrees flexion, whereas
      extension torque was greatest at 50 degrees flexion. Gender-specific differences
      in trunk strength were markedly reduced when the torque data were normalized by
      the subject's height multiplied by body weight. The E/F torque ratio showed a
      relatively linear, over twofold increase with increasing flexion angle, and was
      significantly greater for female subjects compared with male subjects at most
      sagittal postures. The baseline trunk isometric strength data provided by this
      study should help clinicians to use strength testing more precisely and
      specifically in prevention and diagnosis of patients at risk for back disorders.

PMID- 12177550
TI  - Metastatic pudendal nerve compression presenting as atypical sciatica.
AB  - A rare case of Alcock's syndrome caused by tumoral compression of the pudendal
      nerve is reported. Spine surgeons must be aware of the possibility of Alcock's
      syndrome in patients presenting with atypical sciatica.

PMID- 12177549
TI  - Thoracic paraganglioma presenting with spinal cord compression and metastases.
AB  - We report a case of a 41-year-old man with a primary thoracic spine paraganglioma
      presenting with spinal cord compression and distant metastasis. Paragangliomas
      arising within the spinal canal are rare and when they occur are usually found in
      the intradural, extramedullary compartment and in the lumbosacral region.
      Thoracic paragangliomas are very rare, with only five prior cases reported in the
      literature and with distant metastasis seen in only one of these. In this case,
      the tumor was entirely extradural and produced extensive sclerosis of the
      surrounding vertebrae. The clinical, radiographic, and pathologic features of
      this case are detailed and the relevant literature is reviewed.

PMID- 12177551
TI  - Dural ectasia and back pain: review of the literature and case report.
AB  - Dural ectasia is defined as a ballooning of the dural sac which is more common in
      patients with connective tissue disorders such as the Marfan syndrome. Several
      studies have shown that dural ectasia may be associated with such conditions as
      back pain, headaches, radiculopathies, or incontinence. We present a case of a 52
      year old woman with Marfan syndrome who presented with a significantly large
      anterior sacral meningocele without having associated symptoms. In light of this
      case, we recommend that asymptomatic Marfan patients with dural ectasia should be
      closely observed without need for immediate surgical intervention.

PMID- 12177552
TI  - Gluteal artery pseudoaneurysm, a rare cause of sciatic pain: case report and
      literature review.
AB  - This article describes a very unusual case of sciatic pain and motor dysfunction
      resulting from gluteal artery pseudoaneurysm. A 36-year-old woman with primary
      infertility sustained an iatrogenic injury to her left gluteal artery during
      transvaginal ultrasound-guided follicle aspiration. Twenty-five days after the
      procedure she developed severe left sciatic pain and motor dysfunction. Pelvic
      computed tomography and magnetic resonance imaging revealed a huge pelvic
      hematoma. Angiography demonstrated a gluteal artery pseudoaneurysm. Because
      endovascular occlusion of the aneurysm did not relieve the pain, the patient
      underwent surgery for evacuation of the hematoma and release of the lumbosacral
      plexus. This eliminated all her sciatic pain and restored her motor dysfunction
      completely. The English literature details only five other cases of sciatic pain
      resulting from gluteal artery aneurysm, and these reports are also discussed.

PMID- 12177553
TI  - Thoracic outlet syndrome (TOS) is one of the traumatic complications of whiplash
      injury.

PMID- 12177554
TI  - Subacute care in nursing homes.

PMID- 12177555
TI  - Equitable salaries in nursing: how do we get there?

PMID- 12177556
TI  - Profiling and developing nursing leaders.

PMID- 12177557
TI  - The rising tide of healthcare labor unions in nursing.

PMID- 12177558
TI  - Realizing your marketing influence, Part 3: professional certification as a
      marketing tool.
AB  - This is the last in a series of articles guiding nursing administrators from
      broad marketing strategy to tactics and specific applications. The first article
      laid the foundation for developing a market-driven strategic plan. The second
      focused on marketing from the inside out. This final article explores the
      benefits of specialty nurse certification as a strategy for nursing
      administrators to retain and recruit the most qualified nurses and to
      differentiate their services from those of competitors. The article includes
      findings from the American Association of Critical-Care Nurses' proprietary
      research, suggestions on how to support certification, and a case study of one
      hospital's experience in conducting a CCRN certification drive as part of their
      critical care nurse competency program.

PMID- 12177561
TI  - Capacity building of leaders in healthcare organizations: monitoring organization
      wide implementation of the clinical practice model.
AB  - There is a great need for organizational leaders to provide data-based evidence
      that a program or initiative makes a difference. The authors describe findings
      from a survey designed to gather baseline data about changes organizations
      experience after implementing the Clinical Practice Model framework, and report
      how the Clinical Practice Model Resource Center staff used the survey findings to
      build the capacity of individuals accountable for implementing this integrated,
      interdisciplinary professional practice framework into the organization's
      operations.

PMID- 12177560
TI  - Enhancing work climate to improve performance and retain valued employees.
AB  - Organizational climate is the perception of how it "feels" to work in a
      particular work environment. Climate is one of the most powerful, yet overlooked,
      factors when determining the performance of a particular organization or work
      team. Studies have consistently linked climate to individual and organizational
      performance. The author discusses the 6 key dimensions of climate, how to
      evaluate it in an organization, and methods to enhance it.

PMID- 12177559
TI  - Retaining the older nurse.
AB  - The nursing workforce is aging more rapidly than the workforce as a whole, and
      fewer young people are entering the profession. It is imperative that older
      nurses be retained, not only for their experience and expertise, but also to
      prevent worsening an already critical nursing shortage. A descriptive survey
      design was used to determine the knowledge base and plans for the aging RN
      workforce by North Carolina hospitals and nursing homes. Nurses over age 55 made
      up 14.1% of the respondents' RN staff. Most administrators are aware of the aging
      workforce and wish to retain older nurses. Unfortunately, 94% of facilities have
      no policies in place to address the needs of older nurses, and 87% admitted to
      having no immediate plans to do so. Specific recommendations are made to assist
      nurse managers in retaining the older RN.

PMID- 12177563
TI  - Creating healthcare cultures of patient safety.
AB  - With the release of the Institute of Medicine's report on patient safety, a
      national agenda was set to rebuild the public's trust and create cultures of
      safety within all healthcare organizations. This vision of improvement is driving
      changes in healthcare organizations, educational institutions, and regulatory
      agencies to remove the blame and improve their systems. Understanding historical
      events, strategies for organization change, and current patient safety
      initiatives will assist nursing leaders to become active participants at the
      local, state, and national level as cultures are changed and solutions are
      developed to prevent patient injuries.

PMID- 12177562
TI  - Evaluating quality of nursing care: the gap between theory and practice.
AB  - The purpose of this article is to determine whether nursing practice, as judged
      by nurse peer reviewers, varies by type or location of hospital and to assess
      which aspects of practice tend to be most at variance with nursing theory. This
      article provides a framework of continued quality assessment and improvement that
      is based on prior research. Trained nurse peer reviewers carried out structured
      implicit review, which utilized their professional judgment to evaluate the
      process of nursing care for patients admitted to acute hospitals with heart
      failure or cerebrovascular accident. Findings show significant variations in the
      quality of nursing care and support the continued development of nursing quality
      assessment and improvement initiatives directed at reducing the gap between
      nursing theory and practice.

PMID- 12177565
TI  - Analysis of the olfactory capacity of healthy children before language
      acquisition.
AB  - The absence of a method for evaluating the olfaction of infants and children
      without structured language led us to perform a longitudinal study of the
      behavioral responses of very young children. The aim was to establish a tool for
      verifying a child's olfactory ability during a pediatric examination. A total of
      107 subjects were observed and filmed during a regular olfactory activity. Three
      years of filmed observations were analyzed and showed three types of stable
      behavioral responses that we consider to be specific to olfactory stimulus:
      modification of respiratory rhythm, fixed stare, and decrease of mobility. These
      responses were observed for 98% of the subjects in 100% of the first
      presentations of the odorized tissue. Response time was not influenced by age,
      socioeconomic situation, or position in the family, but it was influenced by
      ethnic background. These responses constitute items allowing the first step of an
      objective assessment of a prelanguage child's olfaction without the subject's
      verbal participation.

PMID- 12177564
TI  - Maternal cocaine use: estimated effects on mother-child play interactions in the
      preschool period.
AB  - The study objective was to evaluate the quality of parent-child interactions in
      preschool-aged children exposed prenatally to cocaine. African-American mothers
      and their full-term newborns (n = 343) were enrolled prospectively at birth and
      classified as either prenatally cocaine-exposed (n = 157) or non-cocaine-exposed
      (n = 186) on the basis of maternal self-report and bioassays. Follow-up
      evaluations at 3 years of age (mean age, 40 mo) included a videotaped dyadic play
      session and maternal interviews to assess ongoing drug use and maternal
      psychological distress. Play interactions were coded using a modified version of
      Egeland et al's Teaching Task coding scheme. Regression analyses indicated
      cocaine-associated deficits in mother-child interaction, even with statistical
      adjustment for multiple suspected influences on interaction dynamics. Mother
      child interactions were most impaired in cocaine-exposed dyads when the mother
      continued to report cocaine use at the 3-year follow-up. Multivariate profile
      analysis of the Egeland interaction subscales indicated greater maternal
      intrusiveness and hostility, poorer quality of instruction, lower maternal
      confidence, and diminished child persistence in the cocaine-exposed dyads.

PMID- 12177566
TI  - Can paraprofessional home visitation enhance early intervention service delivery?
AB  - A 1-year randomized trial compared intensive case management (ICM) versus basic
      case management (BCM) in facilitating early intervention (EI) service use among
      children in an urban health system. Of 159 participating families with delayed or
      at-risk preschool-aged children, 88 received ICM from paraprofessionals versus 71
      families who received less comprehensive BCM from a nurse. In the ICM versus BCM
      group, a shorter interval to assessment (98 vs 140 d, p =.05) but similar
      assessment rate (86% vs 80%, p =.29) was observed. The ICM group had more
      services recommended per child (1.64 vs 1.16, p < .004) and initiated (1.20 vs
      0.85, p < .04). There was no difference in median time to EI program initiation
      for ICM versus BCM (228 vs 200 d, p = .88) or initiation and visit compliance
      rate for EI services. Specific efforts to improve outcomes (e.g., decrease
      initiation time and increase use of EI services) are still needed.

PMID- 12177567
TI  - Laboratory pain reactivity and gender: relationship to school nurse visits and
      school absences.
AB  - Currently, there are no clear methods for identifying children vulnerable to
      frequent school absences. Our study examined relationships between gender and
      laboratory pain reactivity to the cold-pressor task (CPT), and parent-involved
      school absences and self-initiated school nurse visits in 57 children (36 female;
      ages 8-10 years). Using multiple regression analyses, CPT pain ratings,
      tolerance, and gender were analyzed in relation to nurse visits and absences
      collected prospectively across 2 years. We found that higher pain ratings and
      female gender predicted more absences; female gender also predicted increased
      nurse visits for acute complaints with documented physical findings. Our results
      suggest that laboratory pain reactivity is a potentially useful indicator of
      vulnerability to parent-involved functional impairment, as indexed by school
      absences, and that girls are more likely than boys to miss school and visit the
      nurse for acute illnesses. Limitations and pathways for further study are
      discussed.

PMID- 12177569
TI  - Feeding patterns of full-term and preterm infants at forty weeks postconceptional
      age.
AB  - Little research exists that addresses the differences in feeding skills between
      preterm (PT) infants at term and full-term (FT) infants. The purpose of this
      study was to quantify and examine the differences in sucking abilities of PT
      infants when measured at 40 weeks postconceptional age (PCA) and newly born FT
      infants. The sample consisted of 213 infants who were divided into three groups
      on the basis of their gestational age at birth (24-29 wk, 30-32 wk, and 38-42
      wk). The Kron Nutritive Sucking Apparatus (KNSA) was used to examine the
      microstructure of sucking and feeding behaviors. There were significant
      differences among the three groups in several of the sucking variables: number of
      bursts (p = .005), intersuck interval (p = .0212), sucks per burst (p = .0003),
      suck width (p < .0001), intersuck width (p < .0001), mean maximum pressure (p <
      .0001), and intersuck width/interburst width (p = .02). The findings from this
      study demonstrate the importance of both maturation at birth and experience as
      factors influencing feeding behaviors.

PMID- 12177568
TI  - Levetiracetam in autistic children: an open-label study.
AB  - The objectives of this study were to determine whether autistic children taking
      levetiracetam (1) showed improvement in the areas of aggression, impulsivity,
      hyperkinesis, and mood instability, and (2) showed a nootropic response. Ten
      white autistic boys ranging from 4 to 10 years were compared pretreatment and
      while taking levetiracetam for an average of 4.1 weeks. Inattention,
      hyperkinesis, and impulsivity were evaluated using the Achenbach Attention
      Problems scale, Conners DSM-IV Total scale, and the Conners Attention-Deficit
      Hyperactivity Disorder Index scale, all of which showed statistically significant
      improvements. Mood instability was measured with the Conners Global Index (CGI)
      Emotional Lability and CGI Total scales, both of which showed statistically
      significant improvements. Aggressive behavior, as measured with the Achenbach
      Aggression scale, showed statistically significant improvement only for subjects
      who were not recently weaned from medications that reduce aggression (e.g.,
      risperidone, carbamazepine, desipramine). Levetiracetam may reduce hyperactivity,
      impulsivity, mood instability, and aggression in autistic children with these
      problems. No nootropic effect was observed.

PMID- 12177570
TI  - Important health provider characteristics: the perspective of urban ninth
      graders.
AB  - Clinicians caring for adolescents may be better positioned to provide health care
      when equipped with an understanding of adolescents' preferences regarding
      provider characteristics. The purpose of this study is to obtain a manageable
      framework of adolescents' concerns about health care providers. A series of
      qualitative and quantitative data-collection methods were used to elicit and
      organize ideas about health care providers from ninth-grade students in
      Philadelphia. A 5-point Likert survey, based on ideas generated and prioritized
      in earlier qualitative stages, was administered in school. Exploratory and
      confirmatory factor analysis was used to uncover latent factors. A total of 2602
      students returned usable surveys. A confirmatory factor analysis model including
      four latent factors (patient's interpersonal relationship with provider, concern
      for physical safety, concern for emotional safety, and provider counseling
      ability) explained 51.6% of the model variability. Urban ninth graders want
      providers with whom they can develop strong relationships, feel emotionally and
      physically safe, and turn to for counseling. Communication with adolescent-aged
      patients should be a standard component of health care training and should
      promote provider sensitivity to adolescent fears and needs in the health care
      setting.

PMID- 12177571
TI  - Outcome correlates of parent-child bedsharing: an eighteen-year longitudinal
      study.
AB  - We report results of the first longitudinal study of outcome correlates of parent
      child bedsharing. Two hundred five families in nonconventional and conventional
      family lifestyles have been followed since 1975. A target child in each family
      was followed from the third trimester of mother's pregnancy through age 18 years.
      Bedsharing in early childhood was found to be significantly associated with
      increased cognitive competence measured at age 6 years, but the effect size was
      small. At age 6 years, bedsharing in infancy and early childhood was not
      associated with sleep problems, sexual pathology, or any other problematic
      consequences. At age 18 years, bedsharing in infancy and childhood was unrelated
      to pathology or problematic consequences, nor was it related to beneficial
      consequences. We discuss these results in light of widespread fears of harm
      caused by parent-child bedsharing. We suggest that such fears are without warrant
      if bedsharing is practiced safely as part of a complex of valued and related
      family practices.

PMID- 12177572
TI  - Cosleeping.

PMID- 12177573
TI  - Pure severe dyslexia after a perinatal focal lesion: evidence of a specific
      module for acquisition of reading.
AB  - A child with a small, residual "localized" perinatally acquired left hemisphere
      temporal tip lesion is described. He presents with pure and severe dyslexia and
      average to high-average cognitive skills, which are usually in the low-average
      range in patients with developmental dyslexia. A highly circumscribed deficit of
      rote auditory verbal memory was the only deficit other than the dyslexia; his
      verbal semantic memory and visuospatial memory were intact. Two previously
      reported cases present a similar functional profile and lesion locus. This
      profile indicates that there may exist, at birth, a localized neural network
      dedicated to "reading acquisition" and that the layout of this network may differ
      from the systems identified as defective in developmental dyslexia, as well as in
      cases of acquired dyslexia in adults.

PMID- 12177574
TI  - Failure to thrive in a four-month-old nursing infant.

PMID- 12177575
TI  - Peer relations of youth with pediatric conditions and health risks: promoting
      social support and healthy lifestyles.
AB  - Peer relations and close friendships play important roles in youngsters'
      emotional development and take on special significance when a child or adolescent
      has a chronic disease. This article reviews the key ways that peer relations have
      been examined in youth with chronic pediatric conditions and specifically focuses
      on (1) the role of peers and close friends as a source of support, (2) friends'
      influence on treatment adherence, and (3) peers' and friends' impact on health
      promoting and health-risk behaviors. In general, youngsters with chronic
      conditions do not have more problems in their peer relations than other youth,
      although children with medical conditions that are stigmatizing or that involve
      the central nervous system (CNS) may encounter peer difficulties. Social support
      from friends and classmates appears to facilitate youngsters' disease adaptation
      and may help with the lifestyle aspects of treatment regimens. Adolescent peer
      crowd affiliations (e.g., "brains," "jocks") that are linked with health
      promoting behaviors may prove beneficial to youngsters' disease management and
      health. The findings underscore the need for helping children and adolescents
      disclose their medical condition to peers in positive ways and for including
      youngsters' close friends in the treatment process and in school-reentry programs
      after extended medical care. Additional research is needed to develop strategies
      for incorporating youngsters' peers and friends into the medical management of
      youth with chronic pediatric conditions.

PMID- 12177581
TI  - Almost one year later: looking back and looking ahead.

PMID- 12177582
TI  - Neonatal psychology is an important area of study.

PMID- 12177583
TI  - A 1-year, double-blind, placebo-controlled trial of ziprasidone 40, 80 and 160
      mg/day in chronic schizophrenia: the Ziprasidone Extended Use in Schizophrenia
      (ZEUS) study.
AB  - We evaluated relapse in patients with stable, chronic schizophrenia over a 1-year
      period; inpatients were randomized to ziprasidone 40 mg/day (n = 72), 80 mg/day
      (n = 68), 160 mg/day (n = 67) or placebo (n = 71). The probability of relapse
      (Kaplan-Meier) at 1 year was significantly lower in the ziprasidone 40, 80, and
      160 mg/day groups (43%, 35% and 36%, respectively) compared to placebo (77%; P =
      0.002, P < 0.001 and P < 0.001, respectively). In those patients who remained on
      treatment for at least 6 months, only 9% subsequently relapsed on ziprasidone
      compared to 42% on placebo (P = 0.001). All three doses of ziprasidone were
      significantly superior to placebo on Positive and Negative Syndrome Scale (PANSS)
      efficacy variables (all P < 0.05). Ziprasidone was associated with a
      significantly greater mean improvement in the PANSS negative symptom subscale
      compared to placebo (P < 0.05). Discontinuation due to adverse events was similar
      with ziprasidone and placebo. Ziprasidone treatment was indistinguishable from
      placebo in assessments of movement disorders and was not associated with weight
      gain or cardiovascular abnormalities. These results demonstrate that ziprasidone
      was effective in reducing the frequency of relapse and was associated with long
      term improvement in negative symptoms. Ziprasidone was well tolerated in this
      population of patients with chronic, stable schizophrenia.

PMID- 12177584
TI  - Discontinuation symptoms: comparison of brief interruption in fluoxetine and
      paroxetine treatment.
AB  - Abrupt interruption or cessation of selective serotonin reuptake inhibitor (SSRI)
      treatment may result in discontinuation or treatment interruption symptoms.
      Recent reports suggested these symptoms occur more frequently with shorter half
      life SSRIs. Previous studies indicated a 5-8-day treatment interruption resulted
      in fewer discontinuation-emergent adverse events in fluoxetine-treated patients
      than in paroxetine-treated patients. This study examines the effects of shorter
      treatment interruption (3-5 days), as would occur if patients miss just a few
      doses of medication. Patients successfully treated for depression with fluoxetine
      or paroxetine underwent treatment interruption in a double-blind fashion.
      Treatment interruption-emergent symptoms were assessed using the Discontinuation
      Emergent Signs and Symptoms checklist. Other assessments included the Montgomery
      Asberg Depression Rating Scale, Clinical Global Impressions-Severity scale and a
      social functioning questionnaire. Of 150 patients enrolled, 141 completed the
      study. Following treatment interruption, fluoxetine-treated patients experienced
      fewer treatment interruption-emergent events than did paroxetine-treated
      patients. The paroxetine treatment group also experienced significant increases
      in depressive symptoms, clinical global severity scores and difficulty in social
      functioning; the fluoxetine treatment group did not. These results are consistent
      with reports suggesting abrupt interruption of treatment with paroxetine is more
      often associated with somatic and psychological symptoms than is abrupt
      interruption of fluoxetine. Patients treated with fluoxetine appeared to be
      protected by its longer half-life.

PMID- 12177585
TI  - Olanzapine versus haloperidol in the treatment of acute mania: clinical outcomes,
      health-related quality of life and work status.
AB  - We aimed to compare clinical outcomes, health-related quality of life (HRQOL) and
      work status associated with olanzapine and haloperidol treatment in patients with
      bipolar disorder. This double-blind, randomized controlled trial, comparing
      flexible dosing of olanzapine (5-20 mg/day, n = 234) to haloperidol (3-15 mg/day,
      n = 219), consisted of a 6-week acute phase, followed by a 6-week continuation
      phase. Symptomatic remission rates were similar for olanzapine- and haloperidol
      treated patients at weeks 6 and 12. At week 6, significant changes in five
      dimensions of the Medical Outcomes Study 36-Item Short Form Health Survey (SF-36)
      [general health (P = 0.010), physical functioning (P < 0.001), role limitations
      due to physical problems (P < 0.001), social functioning (P < 0.05) and vitality
      (P < 0.01)] and the SF-36 physical components summary score were found in favour
      of olanzapine compared to haloperidol. At week 12, olanzapine treatment
      maintained the significantly favourable HRQOL changes. At the end of week 12,
      patients on olanzapine showed significantly greater improvement than haloperidol
      in work activities impairment and household activities impairment scores on the
      Streamlined Longitudinal Interview Clinical Evaluation from the Longitudinal
      Interval Follow-up Evaluation (SLICE/LIFE) activities impairment scores. Subgroup
      analyses revealed that olanzapine treatment significantly increased a proportion
      of employed patients and their weekly paid working hours. In conclusion, compared
      to haloperidol, olanzapine treatment was comparably effective in the remission of
      bipolar mania and significantly improved HRQOL and work status in patients with
      bipolar I disorder.

PMID- 12177587
TI  - Differential effects of high-dose amisulpride versus flupentixol on latent
      dimensions of depressive and negative symptomatology in acute schizophrenia: an
      evaluation using confirmatory factor analysis.
AB  - While many acutely ill schizophrenic patients suffer from depressive symptoms,
      most studies on the efficacy of antipsychotic drugs focus on positive and
      negative symptoms. Dimensional models of schizophrenic symptoms, based on
      confirmatory factor analysis (CFA) using structural equation modelling, offer a
      methodological alternative to compare antipsychotics on empirically justified
      latent factors. The present report is a refined analysis of a published double
      blind study on the D2/D3-selective antagonist amisulpride (ASP) versus the mixed
      D1-5/5-HT2 antagonist flupentixol (FPX). CFA was applied to Brief Psychiatric
      Rating Scale, Scale for the Assessment of Negative Symptoms, Bech-Rafaelsen
      Melancholia Scale and Simpson-Angus Scale subscores to examine differential
      effects of high doses of ASP and FPX on negative and depressive symptom
      dimensions in 126 acutely ill schizophrenic patients. A four-factor model
      comprising the full spectrum of acute symptomatology and a three-factor model
      ('negative', 'anhedonia-apathy', 'depressive') restricted to negative and
      depressive symptoms were yielded with an identical 'depressive' dimension in both
      models. Analyses of CFA-derived factor scores showed that ASP was significantly
      superior to FPX regarding the latent 'depressive' dimension, independent of
      baseline scores, dosage and changes in akinesia. Neither the negative' dimension
      nor 'anhedonia-apathy' showed significantly different treatment effects. CFA
      based analyses appear to be suitable for psychotropic drug evaluation when more
      refined and data-related information on drug efficacy profiles are required.

PMID- 12177586
TI  - Determination of the dose of agomelatine, a melatoninergic agonist and selective
      5-HT(2C) antagonist, in the treatment of major depressive disorder: a placebo
      controlled dose range study.
AB  - Agomelatine (S 20098) has a unique and new pharmacological profile. It is a
      melatoninergic agonist and selective antagonist of 5-HT2C receptors, and has been
      shown to be active in several animal models of depression. The aim of this study
      was to determine the active dose of agomelatine in the treatment of major
      depressive disorder (DSM-IV criteria). The methodology used was a conventional
      double-blind design comparing three different doses of agomelatine (1, 5 and 25
      mg once a day) with placebo over an 8-week treatment period. Paroxetine was used
      as the study validator. Seven hundred and eleven patients with a baseline mean
      score of 27.4 on the 17-item Hamilton Rating Scale for Depression (HAM-D) were
      included. On the pivotal analysis, the mean final HAM-D total score (Full
      Analysis Set LOCF) demonstrated agomelatine 25 mg to be statistically more
      effective than placebo. This was confirmed by other analyses and criteria
      (responders, remission, subpopulation of severely depressed patients, Montgomery
      Asberg Depression Rating Scale, Clinical Global Impression-Severity of Illness).
      Agomelatine 25 mg alleviated the anxiety associated with depression, as measured
      on Hamilton Anxiety Scale. Paroxetine was found to be effective on pivotal
      analysis and most of the secondary criteria used to validate the study
      methodology and population. Agomelatine, whatever the dose, showed good
      acceptability with a side-effects profile close to that of placebo. In
      conclusion, this study demonstrates that agomelatine is efficient in the
      treatment of major depressive disorder and that 25 mg is the target dose.

PMID- 12177588
TI  - Quetiapine-induced improvement of tardive dyskinesia in three patients with
      schizophrenia.
AB  - There are very rare cases indicating the effectiveness of the atypical
      antipsychotics in the treatment of tardive dyskinesia except clozapine. We report
      three patients with schizophrenia who demonstrated improvement of tardive
      dyskinesia following treatment with quetiapine; two of them were unable to use
      clozapine because of intolerable side-effects.

PMID- 12177590
TI  - Frequently asked questions About OBQM/OBQI.

PMID- 12177591
TI  - Congressional advocates speak out for home care.

PMID- 12177592
TI  - Why I would rather do OBQI than lie on a beach!

PMID- 12177594
TI  - A basic and practical overview of the six steps of outcome-based quality
      improvement. Data collection: the basics.

PMID- 12177595
TI  - A basic and practical overview of the six steps of outcome-based quality
      improvement. Data collection: practical application.

PMID- 12177596
TI  - A basic and practical overview of the six steps of outcome-based quality
      improvement. Data processing and transmission: the basics.

PMID- 12177597
TI  - A basic and practical overview of the six steps of outcome-based quality
      improvement. Data processing and transmission: practical application.

PMID- 12177598
TI  - A basic and practical overview of the six steps of outcome-based quality
      improvement. Interpreting outcome reports: the basics.
AB  - Analysis of OASIS data produces several types of agency-level (aggregate)
      reports. This article describes the components of the risk-adjusted and
      descriptive outcome report.

PMID- 12177599
TI  - A basic and practical overview of the six steps of outcome-based quality
      improvement. Interpreting outcome reports: practical application.

PMID- 12177600
TI  - A basic and practical overview of the six steps of outcome-based quality
      improvement. Selecting target outcomes: the basics.
AB  - After obtaining the risk-adjusted and descriptive outcome report, the first
      activity of outcome enhancement involves selecting one or two target outcomes.
      This article outlines the criteria for target outcomes selection and features a
      suggested timeline.

PMID- 12177602
TI  - Helpful OASIS and OBQI resources.

PMID- 12177601
TI  - A basic and practical overview of the six steps of outcome-based quality
      improvement. Selecting target outcomes: practical application.

PMID- 12177603
TI  - My OBQI Experience.

PMID- 12177604
TI  - Estradiol enhances murine cardiac allograft rejection under cyclosporin and can
      be antagonized by the antiestrogen tamoxifen. Transplantation 2002; 74: 354.

PMID- 12177605
TI  - Enforced c-REL deficiency prolongs survival of islet allografts1.
AB  - BACKGROUND: The NF-kappaB/Rel family of transcription factors regulates biologic
      processes ranging from apoptosis to inflammation and innate immunity. Whether c
      Rel, a lymphoid-predominant member of the NF-kappaB/Rel family, is essential for
      transplantation immunity is not known. METHODS: We explored the role of c-Rel in
      the anti-allograft repertory using mice with targeted disruption of the c-Rel
      gene (c-Rel-/-) as recipients of H-2 mismatched islet allografts. Allogeneic
      DBA/2 (H-2d) islets were transplanted into the renal subcapsular space of
      diabetic c-Rel-/- C57BL/6 (H-2b) mice or the c-Rel +/+ C57BL/6 wild-type mice.
      Islet graft survival, cellular traffic into the islet grafts and their phenotype,
      and intragraft expression of cytokines and cytotoxic attack molecules were
      determined at the protein (by immunohistochemistry) and mRNA (by real-time
      quantitative polymerase chain reaction) levels. RESULTS: We found superior islet
      graft survival in the c-Rel-/- recipients compared to c-Rel+/+ C57BL/6
      recipients. Splenocytes from c-Rel-/- mice proliferated poorly compared to
      splenocytes from the c-Rel+/+ mice on stimulation with anti-CD3 mAbs or Con A.
      Peri-islet infiltration composed of T lymphocytes and macrophages was found in
      both c-Rel+/+ recipients and c-Rel-/- recipients, but intra-islet infiltration
      was observed only in c-Rel+/+ recipients. Immunohistologic and molecular studies
      showed impaired T helper-type 1 immunity and decreased intragraft expression of
      cytotoxic attack molecules perforin and granzyme B in c-Rel-/- recipients as
      compared to wild-type recipients. CONCLUSIONS: Our results demonstrate that c-Rel
      is essential for robust rejection of islet allografts and support the idea that
      strategies that impair c-Rel function may be of value for constraining
      alloimmunity and facilitating survival of allogafts.

PMID- 12177606
TI  - Efficient transduction of pancreatic islets by feline immunodeficiency virus
      vectors1.
AB  - BACKGROUND: Pancreatic islets transplanted into immunocompetent diabetic subjects
      are rapidly lost to apoptotic or lytic death or both. Genetic engineering of
      islets before transplantation with protective genes may enhance their
      posttransplantation survival. Accomplishing this goal requires the development of
      a safe, efficient vector for islet gene delivery. METHODS: The ability of feline
      immunodeficiency virus (FIV) vectors to transfer a green fluorescent protein
      (GFP) gene to NIT-1 cells and primary islets was measured and compared with
      murine leukemia virus (MLV) and human immunodeficiency virus (HIV) vectors.
      Islets were examined using confocal microscopy to determine the extent and
      pattern of infection. Toxicity of the procedure was assessed via measurement of
      glucose stimulation indices and by reversion of diabetic mice using either FIV
      infected or control islet transplants. RESULTS: FIV effectively transduces islets
      with no untoward effect on the insulin secretion capacity of the beta cells. When
      FIV, HIV, and MLV GFP vectors were standardized to the same 293 cell titer and
      used to infect NIT-1 cells or whole islets, the FIV transduced equal or greater
      numbers of cells relative to the HIV vector and significantly more than the MLV
      vector. Islets transduced with FIV GFP were transplanted in a murine model for
      diabetes and were shown to revert diabetes and express GFP 4 weeks after
      transduction and 3 weeks after transplantation. CONCLUSIONS: FIV transduction is
      a nontoxic and efficient method to genetically modify pancreatic islets and may
      prove promising for delivering genes to augment islet survival after
      transplantation.

PMID- 12177607
TI  - Recipient hypertension potentiates chronic functional and structural injury of
      rat renal allografts.
AB  - BACKGROUND: Systemic hypertension affects many allograft recipients, is an
      important risk factor for chronic graft dysfunction, and is linked to reduced
      graft survival. The condition may up-regulate the expression of inflammatory host
      cells and their products. These, in turn, may significantly injure vascular
      endothelium and other components of allografted kidneys. METHODS: Lewis rats
      received orthotopic F344 renal allografts, a standard model of chronic rejection.
      Renovascular hypertension was produced by placing a silver clip (0.25 mm) on the
      renal artery of the retained contralateral native kidney 4 weeks after
      transplantation. Sham-clipped rats served as normotensive controls. Four
      recipient groups (Gp) were studied: Gp 1, rats with an allograft plus a clipped
      native kidney; Gp 2, those with an allograft and a sham-clipped native kidney; Gp
      3, isografted animals with a clipped native kidney; and Gp 4, those bearing an
      isograft and a sham-clipped native kidney. Systolic blood pressure and
      proteinuria were measured every 2 weeks for 24 weeks. Grafts were assessed
      serially for morphologic and immunohistologic changes. RESULTS: Systemic blood
      pressure rose to hypertensive levels in Gps 1 and 3 within a week of clipping but
      never increased in Gps 2 and 4. Proteinuria developed in hypertensive animals but
      remained at baseline in normotensive controls. Intimal thickening of allograft
      arteries progressed to luminal obliteration with extensive perivascular and
      interstitial fibrosis by 24 weeks. In contrast, vascular changes in isografts of
      hypertensive hosts were restricted to medial hypertrophy. Tumor necrosis factor
      (TNF)-alpha, transforming growth factor (TGF)-beta, platelet derived growth
      factor (PDGF), endothelin, Il-6, major histocompatibility complex (MHC) class II,
      and B7 were up-regulated in allografts in hypertensive hosts. Vascular deposition
      of immunoglobulin (IgG) was increased. These changes were markedly less
      pronounced in Gp 3 isografts and minimal in the kidneys of the normotensive
      animals of Gps 2 and 4. CONCLUSIONS: An experimental model is presented that
      examines the influence of recipient hypertension in the pathogenesis of chronic
      dysfunction and injury developing in rat renal allografts over time.

PMID- 12177608
TI  - CD154-CD40 T-cell costimulation pathway is required in the mechanism of hepatic
      ischemia/reperfusion injury, and its blockade facilitates and depends on heme
      oxygenase-1 mediated cytoprotection.
AB  - BACKGROUND: Ischemia/reperfusion (I/R) injury remains an important clinical
      problem that affects both early and later allograft outcome. This study was
      designed to analyze the role of T cells and CD154-CD40 T- cell costimulation
      pathway in a mouse liver I/R model. METHODS AND RESULTS: Ninety minutes of warm
      ischemia followed by 4 h of reperfusion in wild-type (WT) mice resulted in a
      significant hepatic damage, as assessed by liver function (serum alanine
      aminotransferase [sALT] levels), local neutrophil accumulation (myeloperoxidase
      activity), and histology (Suzuki's score). In contrast, T-cell deficiency (in T
      cell deficient [nu/nu] mice), disruption of the CD154 signaling (in knockout [KO]
      mice), or its blockade in WT recipients (after MR1 monoclonal antibody [mAb]
      treatment), virtually prevented hepatic I/R insult. Unlike CD154-deficient T
      cells, adoptive transfer of WT spleen cells fully restored hepatic I/R injury in
      nu/nu mice. Finally, the improved hepatic function in CD154 KO recipients, WT
      mice treated with CD154 mAb, or nu/nu mice infused with CD154-deficient cells
      resulted in consistently enhanced expression of heme oxygenase-1 (HO-1), a heat
      shock protein with cytoprotective functions. CONCLUSION: This study confirms the
      importance of T cells, and documents for the first time the role of CD154
      costimulation signals in the mechanism of hepatic I/R injury. We also show that
      CD154 blockade-mediated cytoprotection results and depends on HO-1
      overexpression. Our data provide the rationale for human trials to target CD154
      CD40 costimulation in hepatic I/R injury, particularly in the transplant patient.

PMID- 12177610
TI  - Benefit of phosphodiesterase 4 inhibitors as supplemental therapy after lung
      transplantation concerning their antiproliferative effects: an experimental study
      using a heterotopic rodent model.
AB  - BACKGROUND: Recent advances in the understanding of immunomodulatory properties
      of phosphodiesterase 4 (PDE4) inhibitors recommend these drugs for
      immunosuppressive therapy after lung transplantation. The potency of three PDE4
      inhibitors was tested using an established model of heterotopic tracheal
      transplantation in rats. METHODS: Five allogenic groups were investigated and
      treated with the PDE4 inhibitors: rolipram, cilomilast (Ariflo, SB-207499,
      SmithKline Beecham, Munich, Germany), roflumilast (Altana Pharmacia, Bad Homburg,
      Germany) or cyclosporine A (CsA), or left without immunosuppression. The grafts
      were quantitatively analyzed for epithelial integrity, monocyte/macrophage
      content, cell proliferation, and tracheal obliteration by
      histology/immunohistochemistry (days 1, 5, 7, 21, 28; n=4-7). RESULTS: In animals
      treated with the PDE4 inhibitors, the epithelium was completely lost until day
      21. The epithelium was partially preserved in the rats receiving CsA until day
      28. In the acute phase (days 5 and 7) the infiltration of monocytes and
      macrophages was significantly inhibited similarly (cilomilast) or less effective
      (rolipram, roflumilast) as in CsA-treated rats. In the chronic phase (day 28) the
      significant increase of monocytes and macrophages after CsA-treatment was not
      found in PDE4 inhibitor-treated rats. The PDE4 inhibitors showed lower (rolipram)
      or higher (cilomilast, roflumilast) potency as CsA to inhibit the cell
      proliferation. Only treatment with PDE4 inhibitor (Ariflo) significantly
      inhibited the obliteration, but to a lesser degree as CsA. CONCLUSION: The PDE4
      inhibitors tested in our study are not suitable on their own for
      immunosuppressive therapy after lung transplantation because of the limited
      protection against the epithelial disturbance, infiltration of immune cells, and
      luminal obliteration. The strong anti-proliferative effect of the second
      generation PDE4 inhibitors, cilomilast and roflumilast, suggest a benefit for the
      effective inhibition of immune cell and fibroblast proliferation contributing to
      the development of obliterative bronchiolitis.

PMID- 12177609
TI  - Effects of a p38 mitogen-activated protein kinase inhibitor as an additive to
      Euro-Collins solution on reperfusion injury in canine lung transplantation1.
AB  - BACKGROUND: The activation of p38 mitogen-activated protein kinase (MAPK) plays
      an important role in the development of ischemia/reperfusion injury. FR167653 is
      a novel p38 MAPK inhibitor. This study evaluated the effects of p38 MAPK
      inhibition during cold ischemia on subsequent reperfusion injury using FR167653
      as an additive to Euro-Collins solution in canine lung transplantation. METHODS:
      Canine orthotopic left lung transplantation was performed after 12-hr cold
      storage using Euro-Collins solution, with or without FR167653. Fifteen minutes
      after reperfusion, the right pulmonary artery and the right stem bronchus were
      ligated, and the animals were observed for 4 hr after reperfusion. Left pulmonary
      vascular resistance (L-PVR), cardiac output (CO), arterial oxygen pressure
      (Pao2), and alveolar-arterial oxygen pressure difference (A-aDo2) were measured.
      Lung specimens were harvested for wet-to-dry lung weight ratio (WDR)
      measurements, histopathologic studies, and polymorphonuclear neutrophil (PMN)
      counts. The activities of p38 MAPK in lung grafts were evaluated. RESULTS: The
      addition of FR167653 significantly (P<0.05) improved Pao2, A-aDo2, L-PVR, CO, and
      WDR and suppressed PMN infiltration after transplantation. FR167653 also
      ameliorated histologic damage to the lung graft. During cold storage, p38 MAPK
      was not activated in the lung graft, whereas it was markedly activated 30 min
      after reperfusion. FR167653 significantly (P<0.05) inhibited p38 MAPK activation
      30 min after reperfusion. CONCLUSIONS: The addition of FR167653 to Euro-Collins
      solution improved lung graft viability associated with the inhibition of p38 MAPK
      activation. These results suggest that inhibiting p38 MAPK activation may
      attenuate ischemia/reperfusion injury in lung transplantation.

PMID- 12177611
TI  - Induction of xenograft accommodation by modulation of elicited antibody
      responses1 2.
AB  - BACKGROUND: We have established that the timing of splenectomy influences the
      magnitude of the xenoreactive antibody (XAb) response and thus hamster heart
      survival in cyclosporine (CyA)-treated rats. This model has been used to test our
      hypothesis that modulation of XAb responses without perturbation of complement
      may influence the development of graft accommodation. METHODS: Pretransplantation
      splenectomy (day -1/day 0) fully abrogated anti-graft IgM response, whereas a
      delayed procedure (day 1/day 2) caused significantly delayed (3-4 days) and
      decreased levels (two- to threefold) of XAb. Both interventions resulted in long
      term graft survival. After surviving for 7 or more days, xenografts in CyA
      treated rats with post-, but not pre-, transplantation splenectomy were also
      resistant to exogenous anti-graft XAb. Such grafts meet the criteria for
      accommodation. Accommodating hearts displayed progressive and increasing
      expression of protective genes, such as heme oxygense (HO)-1 and A20, in
      endothelial cells and smooth muscle cells. RESULTS: Our results suggest that XAb
      responses may influence the kinetics of accommodation development possibly by
      promoting protective gene expression. This hypothesis was directly tested in
      vitro. Pretreatment of porcine aortic endothelial cells with sublytic amounts of
      baboon anti-pig serum for 24 hr induced HO-1 expression; this was associated with
      cell resistance to lytic amounts of such serum. Overexpression of HO-1 by
      adenoviral-mediated gene transfer in porcine aortic endothelial cells resulted in
      similar protective effects. CONCLUSIONS: Delayed and relatively low levels of XAb
      IgM promote expression of protective genes in the graft and thereby aid in the
      progress of accommodation. Expression of HO-1 protects xenoserum-mediated
      endothelial cell destruction.

PMID- 12177612
TI  - Allograft tolerance induced by intact active bone co-transplantation and anti
      CD40L monoclonal antibody therapy.
AB  - BACKGROUND: One of the most promising approaches to achieving allograft tolerance
      involves the transient inhibition of co-stimulatory signals in T cells. There is,
      however, increasing evidence that this approach alone cannot universally elicit
      allograft tolerance and that adjunct therapies capable of synergizing with co
      stimulation blockade may be necessary. METHODS: We developed a novel tolerance
      strategy involving co-transplantation of intact allogeneic bone fragments
      containing active bone marrow (intact active bone [IAB]) with heart allograft and
      transient anti-CD40L monoclonal antibody therapy. RESULTS: Mice treated with IAB
      and anti-CD40L were tolerant to major histocompatibility complex and minor
      antigen-mismatched cardiac and skin allografts. Heart allografts had normal
      histology up to 270 days posttransplantation, and the production of graft
      reactive antibodies was inhibited. Microchimerism, but no macrochimerism, of
      donor cells was detected in the peripheral blood or lymphoid organs of tolerant
      mice receiving IAB and anti-CD40L. Lymphocytes from tolerant mice retained normal
      proliferative responsiveness to donor cells in vitro but demonstrated a donor
      specific loss in the priming of interferon-gamma responses. The ability to
      produce interleukin-2 or -4 when stimulated with donor cells was normal.
      CONCLUSIONS: Contrary to previous reports of the ability of bone marrow cells to
      induce central deletional tolerance, our data suggest that the regimen involving
      co-transplantation of IAB on the day of heart allograft transplantation and
      transient anti-CD40L therapy induces a robust donor-specific peripheral
      tolerance.

PMID- 12177613
TI  - Estradiol enhances murine cardiac allograft rejection under cyclosporin and can
      be antagonized by the antiestrogen tamoxifen.
AB  - BACKGROUND: An increased incidence of acute rejection episodes in female heart
      transplant recipients has been reported in experimental and clinical studies.
      However, the exact mechanisms of gender-specific differences in alloreactivity
      are not completely understood. METHODS: C57BL/10 (H-2b) hearts were transplanted
      into C3H/He (H-2 k) recipients. Four gender combinations were used to test the
      influence of donor and recipient sex on graft survival. Recipients were treated
      with CsA, 17beta-estradiol and/or tamoxifen. Additionally mice were
      ovariectomized prior to transplantation. RESULTS: Treated with CsA, allograft
      survival in female recipients was 9.16+/-0.41 days as compared with 15.16+/-1.72
      days in males. Estradiol administration and oophorectomy had a significant impact
      on allograft survival in male and female mice under CsA treatment. Tamoxifen
      combined with CsA significantly prolonged graft survival in female recipients
      (13.16+/-1.16 days) as compared with CsA treatment alone (9.16+/-0.41 days).
      CONCLUSION: Female mice show earlier rejection episodes and a shorter graft
      survival than males. For the first time, tamoxifen has been shown to have a
      beneficial effect on heart allograft survival in female recipients.

PMID- 12177614
TI  - Transplant tumor registry: donor related malignancies.
AB  - BACKGROUND: Transmission of donor malignancies has been intermittently reported
      since the early days of clinical transplantation. The incidence of United States
      donor related malignancies has not previously been documented. METHODS: All donor
      related malignancies reported to the Organ Procurement and Transplantation
      Network/United Network for Organ Sharing from 4/1/94-7/1/01 in a cohort of 34,933
      cadaveric donors and 108,062 recipients were investigated by contacting the
      transplant centers to verify that the reported tumors were of donor origin. Time
      and mode of discovery, as well as graft and patient outcome, were determined. The
      status of other recipients from the donor was investigated. RESULTS: A total of
      21 donor related malignancies from 14 cadaveric and 3 living donors were
      reported. Fifteen tumors were donor transmitted and 6 were donor derived.
      Transmitted tumors are malignancies that existed in the donor at the time of
      transplantation. Derived tumors are de novo tumors that develop in transplanted
      donor hematogenous or lymphoid cells after transplantation. The cadaveric donor
      related tumor rate is 0.04% (14 of 34,993). The donor related tumor rate among
      transplanted cadaveric organs is 0.017% (18 of 108,062). Among patients
      developing donor related malignancies, the overall mortality rate was 38%, with
      that of transmitted tumors being 46% and derived tumors being 33%. The cadaveric
      donor related tumor mortality rate is 0.007% (8 of 108,062). CONCLUSIONS: The
      United States incidence of donor related tumors is extremely small. The donor
      related tumor death rate is also extremely small, particularly when compared with
      waiting-list mortality.

PMID- 12177615
TI  - Risk factors for fractures in kidney transplantation.
AB  - BACKGROUND: Risk factors for fracture after kidney transplantation need to be
      identified to target patients most likely to benefit from preventive measures.
      METHODS: Medical records were reviewed for 1572 kidney transplants done at a
      single center between February, l963 and May, 2000 with 6.5+/-5.4 years of follow
      up. RESULTS: One or more fractures occurred in 300 (19.1%), with multiple
      fractures in 101 (6.4%). After excluding fractures of the foot or ankle (n=130
      transplants, 8.3%), avascular necrosis (n=86, 5.5%), and vertebral fractures
      (n=28, 1.8%), there were one or more fractures in 196 (12.5%), with a cumulative
      incidence of 12.0%, 18.5%, and 23.0% at 5, 10, and 15 years, respectively. In
      multivariate Cox proportional hazards analysis, age had no effect on fractures in
      men. Compared with men and younger women, women 46-60 and >60 years old were,
      respectively, 2.11 (95% confidence interval 1.43-3.12, P=0.0002) and 3.47 (2.16
      5.60, P<0.0001) times more likely to have fractures. Kidney failure from type 1
      and 2 diabetes increased the risk by 2.08 (1.47-2.95, P<0.0001) and 1.92 (1.15
      3.20, P=0.0131), respectively. A history of fracture pretransplant increased the
      risk by 2.15 (1.49-3.09, P<0.0001). Each year of pretransplant kidney failure
      increased the risk by 1.09 (1.05-1.14, P<0.0001). Obesity (body mass index >30
      kg/m2) was associated with 55% (17-76%, P=0.0110) less risk. Different
      immunosuppressive medications, acute rejections, and multiple other factors were
      not independently associated with fractures. CONCLUSIONS: The population of
      transplant patients at high risk for fracture can be identified using age/gender,
      pretransplant fracture history, diabetes, obesity, and years of pretransplant
      kidney failure.

PMID- 12177616
TI  - Response of elevated Epstein-Barr virus DNA levels to therapeutic changes in
      pediatric liver transplant patients: 56-month follow up and outcome.
AB  - BACKGROUND: Posttransplant lymphoproliferative disease (PTLD) is a serious
      complications after liver transplantation. Epstein-Barr virus (EBV) load measured
      by quantitative competitive polymerase chain reaction (PCR) has been used as an
      early marker for the development of PTLD and a guide for initiating preemptive
      therapy. The aim of this study is to report the results of EBV DNA PCR screening
      in a transplant population and to examine the risk factors for developing
      elevated EBV DNA PCR and the effect of interventions for reducing EBV DNA levels.
      METHODS: Medical records of 44 children who underwent liver transplantation and
      EBV DNA PCR screening during a 3-year period were reviewed, and the patients were
      prospectively followed up for another 2 years. Eleven patients who developed
      elevated EBV DNA PCR levels, defined as >/=40 genomes/105 peripheral blood
      lymphocytes (PBL) in pretransplant EBV-seronegative patients and >/=200
      genomes/105 PBL in pretransplant-seropositive patients, were treated. The initial
      intervention was reduction of immunosuppression and initiation of anti-viral
      therapy in all patients, with administration of cytomegalovirus immunoglobulin
      (CMV-IgG) in two patients. CMV-IgG was then given to five of the patients who did
      not respond to the initial intervention. RESULTS: The initial intervention
      resulted in the reduction of EBV DNA PCR levels to below threshold values in 4 of
      11 patients. Five patients who did not respond to the initial interventions were
      subsequently given intravenous CMV-IgG. The EBV DNA PCR level fell in all five of
      these patients during the course of treatment with CMV-IgG, with a significant
      reduction (to threshold levels or by two dilutions) in four of the five patients.
      No episodes of graft rejection were observed. CONCLUSION: Eleven patients (25%)
      developed elevated EBV DNA PCR after liver transplantation. There were no
      identifiable risk factors for developing elevated EBV DNA PCR. A combination of
      reducing immunosuppression, adding antiviral agents, and initiating CMV-IgG
      resulted in a significant reduction of EBV DNA levels in nine (82%) patients
      during the follow-up period.

PMID- 12177617
TI  - A new model of hepatitis B virus reinfection: liver transplantation in the
      woodchuck1.
AB  - BACKGROUND: Reinfection of liver grafts with hepatitis B virus (HBV) is a
      pertinent problem in clinical liver transplantation, requiring the development of
      new treatment strategies. However, no animal model is currently available to
      study the course and mechanism of hepatitis B reinfection. This was the reason to
      establish the technique of liver transplantation in the woodchuck, which is a
      widely used animal model for HBV infection. MATERIAL AND METHODS: For the
      reinfection study, woodchuck hepatitis virus (WHV)-negative animals were selected
      as donors, whereas chronic carriers served as recipients (n=3). Immunosuppression
      consisted of cyclosporine in a daily dose of 5 mg/kg. Blood and liver samples
      were obtained before and 8 hr, 3 weeks, and 10 weeks after transplantation.
      Virological markers included serological testing for WHV DNA, WHV surface antigen
      (WHsAg), core antigen (WHcAg), and their antibodies (anti-WHs and anti-WHc). WHV
      DNA replication intermediates and viral RNA were detected by Southern blot
      hybridization and Northern blot, respectively. Viral proteins in the liver were
      visualized by immunohistochemistry for WHsAg and WHcAg. RESULTS: Early after
      transplantation membranous but no intracytoplasmic staining for WHsAg was
      detected in the liver graft, which was negative for WHcAg as well as WHV-DNA and
      RNA. Nearly all hepatocytes in the liver grafts of animals killed at 3 weeks and
      10 weeks posttransplant showed strong membranous (WHsAg) and intracytoplasmic
      (WHsAg and WHcAg) staining, which was higher in frequency and intensity than in
      carriers before transplantation. The apparently reduced level of WHV replication
      intermediates and viral RNA in the reinfected liver grafts compared with the
      carrier animals was caused by the severe morphological changes leading to a
      replacement of hepatocytes by extended portal infiltrates. CONCLUSION: The
      woodchuck proved to be a suitable model to study WHV reinfection after liver
      transplantation, because the operative procedure was well tolerated. The first
      sign of viral presence in the graft was WHsAg detected exclusively in the
      sinusoids. Reinfection was proven by heavy intracytoplasmic staining for WHsAg
      and WHcAg in the majority of hepatocytes and detection of viral DNA and RNA in
      the graft.

PMID- 12177618
TI  - Host responses after acellular muscle basal lamina allografting used as a matrix
      for tissue engineered nerve grafts1.
AB  - BACKGROUND: A nerve gap must be bridged by autologous nerve grafts that serve as
      scaffold and consist of viable Schwann cells that promote regeneration. Owing to
      the necessary immunosuppression, nerve allografts remain limited to special
      cases. Alternatively, tissue engineering of peripheral nerves focuses on the
      implantation of cultured Schwann cells into suitable scaffolds. We established
      grafts from Schwann cells and basal lamina from acellular muscles. These grafts
      offer a regeneration that is comparable to autologous nerve grafts. METHODS:
      Using a rat model (DALEW.1W strain), the present study evaluates the host
      response to acellular muscle allografts by assessing cellular reaction major
      histocompatability (MHC) class I and II, lymphocytes, macrophages. The results
      were compared to untreated muscle allografts. RESULTS: Macroscopically, the
      untreated muscles showed a strong inflammatory reaction as a sign of rejection,
      whereas the acellular muscle offered only minor reactions in the periphery of the
      graft. Expression of MHC I and II and invasion of CD4/CD8 positive cells and
      macrophages was pronounced after grafting the untreated muscles. Only a moderate
      reaction was noted for these parameters after acellular grafting. CONCLUSIONS:
      The acellular muscle graft is not completely free of cellular response; however
      the reaction is considered to be moderate and is located only in the periphery.
      To date, synthetic scaffolds that represent endoneurial tube-like structures and
      allow sufficient adhesion of Schwann cells and axonal regeneration are not
      available. The decreased response to acellular muscle allografts offers at least
      a basis for further experiments.

PMID- 12177619
TI  - Chronic antagonism of Mig inhibits cellular infiltration and promotes survival of
      class II MHC disparate skin allografts.
AB  - BACKGROUND: The goal of the current study was to test the ability of monokine
      induced by IFN-gamma (Mig)-specific antibodies to inhibit long-term T cell
      infiltration into class II major histocompatibility complex (MHC) disparate skin
      allografts and to test cellular and molecular changes in the graft during the
      rejection observed following cessation of treatment. METHODS: C57BL/6 recipients
      of B6.H-2bm12 skin grafts were treated with normal rabbit serum (NRS) or rabbit
      Mig antiserum (Mig AS) every other day from day 7 until day 21 posttransplant and
      then weekly thereafter. Allografts were retrieved during the course of treatment
      and following cessation. Tissue sections were prepared and stained to compare
      infiltration by macrophages and CD4+ and CD8+ T cells and to assess collagen
      deposition in the grafts. RNA was prepared and tested by ribonuclease protection
      assay for intragraft levels of Mig, monocyte chemotactic protein-1 (MCP-1) and
      regulated on activation normal T-cell expressed and secreted (RANTES). RESULTS: T
      cell and macrophage infiltration into allografts was inhibited and graft survival
      maintained as long as Mig-specific antibodies were given. Following cessation of
      treatment, T cells and macrophages infiltrated the allografts. In contrast to the
      histology of acute rejection observed in allografts from NRS-treated recipients,
      the resulting rejection of the allografts from Mig AS-treated recipients was
      accompanied by dense collagen deposition and high level expression of Mig and
      RANTES. CONCLUSIONS: Mig directs T cell infiltration into B6.H-2bm12 skin
      allografts on C57BL/6 recipients. Delayed T cell and macrophage infiltration and
      rejection of the grafts following cessation of Mig AS treatment results in
      rejection that is histologically and molecularly distinct from acute rejection.

PMID- 12177620
TI  - Constitutive activation of Jak/STAT proteins in Epstein-Barr virus-infected B
      cell lines from patients with posttransplant lymphoproliferative disorder.
AB  - BACKGROUND: Posttransplant lymphoproliferative disease (PTLD) is a major
      complication after bone marrow and solid organ transplantation. The disease
      encompasses a spectrum of abnormal, Epstein-Barr virus (EBV)-associated B-cell
      proliferations. We have previously shown that EBV-infected, spontaneous
      lymphoblastoid cell lines (SLCL) derived from PTLD patients require autocrine
      interleukin (IL)-10 to proliferate. To determine if cytokine signal transduction
      is involved in the autonomous growth of the SLCL, the activation states of the
      Jak/STAT signaling pathway proteins were analyzed in three different SLCL, termed
      JB7, MF4, and VB4. METHODS: The tyrosine phosphorylation (P-tyr) states of the
      Janus kinases (Jaks) and signal transducers and activators of transcription
      (STAT) proteins were examined by immunoprecipitation and immunoblot. Activated
      STAT dimer formation was determined by electromobility shift assays. RESULTS: All
      three SLCL, but not the Daudi Burkitt's lymphoma B-cell line, expressed the four
      known Jak kinases constitutively tyrosine phosphorylated, with particularly high
      levels of P-tyr Jak1 in the JB7 line. STAT1 and STAT3, but not STAT2 or STAT5,
      are also constitutively activated in all SLCL. The ability of the activated STAT
      proteins to form DNA-binding dimers was confirmed by electromobility shift assay.
      The SLCL, but not the Daudi line, express activated STAT complexes composed of
      STAT1 and STAT3. Another EBV-infected B-cell line, isolated from a lymph node
      biopsy after kidney transplantation, is phenotypically similar to the other SLCL
      in both surface antigen and activated STAT1 and STAT3 expression. CONCLUSION:
      These data support the presence of a constitutively active autocrine signaling
      pathway consistent with IL-10 in the SLCL.

PMID- 12177621
TI  - A novel technique for en bloc, vascularized, composite thymic, and cardiac co
      transplantation1.
AB  - BACKGROUND: A surgical technique for co-transplantation of fully vascularized
      thymus and heart potentially applicable to the clinical setting has not been
      developed and is the subject of this article. METHODS: Vascularized right lobe of
      the thymus was transplanted heterotopically with the heart as a composite graft
      in rats. This co-transplantation technique was developed and assessed, and
      viability of the grafted thymus was evaluated histologically. RESULTS: Surgical
      mortality was identical to isolated heart transplantation, and all grafted hearts
      functioned well. Histology of the thymic grafts at explantation revealed viable
      thymus with preservation of normal thymic microarchitecture. CONCLUSION: We
      developed a novel technique to create a composite graft in which fully
      vascularized and viable thymus was harvested en bloc and co-transplanted with a
      donor heart allograft.

PMID- 12177622
TI  - Multivisceral transplantation for portal hypertension and diffuse mesenteric
      thrombosis caused by protein C deficiency.
AB  - BACKGROUND: Protein C is a vitamin K-dependent glycoprotein synthesized in the
      liver. Homozygous deficiency usually manifests as purpura fulminans in infancy
      and is often fatal. An unlikely, but potentially life-threatening, manifestation
      of protein C deficiency is mesenteric venous thrombosis. METHODS: A patient with
      undiagnosed familial protein C deficiency and a history of intestinal infarction
      developed refractory duodenal and jejunal variceal bleeding as a result of
      diffuse visceral splanchnic thrombosis and portal hypertension. Because his life
      threatening bleeding was unresponsive to all therapies, we performed
      multivisceral transplantation. RESULTS: Multivisceral transplantation cured the
      patient's underlying disease and was lifesaving. Functional protein C,
      undetectable before transplantation, was normal after transplantation. He was
      discharged tolerating a normal diet and is alive at home 6 months later.
      CONCLUSIONS: Multivisceral transplantation should be considered as a treatment
      option for patients with diffuse mesenteric thrombosis, even in the absence of
      short gut syndrome, when portal hypertension causes life-threatening
      complications unresponsive to less aggressive therapies.

PMID- 12177623
TI  - Limited lamivudine and long-term hepatitis B immunoglobulin immunoprophylaxis for
      prevention of hepatitis B recurrence after liver transplantation.
AB  - BACKGROUND: No consensus exists concerning dosage and duration of prophylactic
      hepatitis B immunoglobulin and lamivudine for prevention of hepatitis B
      recurrence after liver transplantation (LT). METHODS: Lamivudine was discontinued
      12 months after LT, maintaining hepatitis B immunoglobulin prophylaxis in eight
      patients who received lamivudine treatment before LT. RESULTS: At LT, six
      patients were serum hepatitis B virus (HBV)-DNA negative, whereas two patients
      had low serum HBV-DNA levels. Hepatitis B surface (HBs) antigen and hepatitis B
      core antigen stained positively by immunohistochemistry in all hepatectomy
      specimens. All patients remained recurrence free during the 12 months on
      combination therapy with normal liver histological examination and negative HBs
      and HB core staining on biopsy specimens. No relapse occurred after lamivudine
      withdrawal during a median follow-up of 17.5 months (normal transaminases,
      negative serum HBs antigen, and HBV-DNA). CONCLUSIONS: Discontinuation of
      lamivudine 12 months after LT is feasible and safe even in patients with ongoing
      low viral replication at LT, providing adequate prophylaxis with hepatitis B
      immunoglobulins.

PMID- 12177624
TI  - T-tube removal after liver transplantation: a new technique that reduces biliary
      complications.
AB  - This article discusses a new simple, fast, and easily performed technique that
      allows reduction of morbidity and hospital stay after T-tube removal. A
      retrospective analysis was conducted of 145 recipients who underwent T-tube
      removal 3 months after orthotopic liver transplantation. Patients were divided in
      two groups: group 1 (n=93) underwent T-tube removal and contemporary placement
      under fluoroscopic guidance of a counter-drain. Group 2 (n=52) T-tubes were
      removed from the bile duct under fluoroscopy but were left in place as a counter
      drain. Overall, there were 33 (22.7%) complications related to T-tube removal.
      Treatment was always conservative and no deaths were related to T-tube. In group
      1, 29 (31.2%) complications occurred; and the mean hospital stay was 9.4+/-9.3
      days. In group 2, four complications (7.7%) occurred (P=0.002); and the mean
      hospital stay was 5.8+/-5.5 days (P=0.012). The adoption of this new technique
      under fluoroscopic guidance, using the T-tube itself as a counter-drain-for T
      tube removal allowed us to significantly reduce biliary complications and
      hospital stay.

PMID- 12177625
TI  - Renal transplantation with venous drainage through the superior mesenteric vein
      in cases of thrombosis of the inferior vena cava.
AB  - Renal transplantation usually is performed by placing the graft in the iliac
      fossa, anastomosing the renal vein to the iliac vein or, when this is not
      possible, to the vena cava. When vascular complications occur, particularly on
      the venous side, the position of the graft may have to be changed. This report
      describes orthotopic renal grafts and positioning of the organ with anastomosis
      to the splenic vessels. Venous drainage was established directly into the
      mesenteric-portal territory, with two cases to the portal vein and one to the
      inferior mesenteric vein. A new technique for the venous drainage of the renal
      graft is shown. We have used this model in two cases of infrarenal inferior vena
      cava thrombosis. The kidney was located in a retroperitoneal position, with
      venous drainage to the superior mesenteric vein through an orifice in the
      posterior peritoneum.

PMID- 12177626
TI  - Taking organs from the young to give to the old: is this acceptable?

PMID- 12177627
TI  - Should all living donors be treated equally?
AB  - Recently, Matas et al. described a protocol to accept as potential donors
      altruistic strangers who offer to donate a kidney to any patient on the waiting
      list. The selection of donors would be the same as the process they use for
      living, emotionally related donors, except that the full work-up would have to be
      done at their institution and would include a detailed psychosocial evaluation.
      In this article, we present a case that raised the question of whether the
      medical standards for nonemotionally related donors should be the same as the
      standards for emotionally related donors. We argue that we must distinguish
      between the altruistic donation by a stranger and the voluntary donation by an
      emotionally related individual. We argue that voluntary donations have a degree
      of moral obligation based on intimacy and that intimacy allows, but does not
      require, that these donors take on slightly additional risk.

PMID- 12177629
TI  - Justification of living-organ donation requires benefit for the donor that
      balances the risk: Commentary on Ross et al.

PMID- 12177630
TI  - Strangers, intimates, and altruism in organ donation.

PMID- 12177632
TI  - Common electrocardiographic artifacts mimicking arrhythmias in ambulatory
      monitoring.
AB  - BACKGROUND: Ambulatory electrocardiographic monitoring is used in clinical
      practice as a means of detecting cardiac arrhythmias during daily activities.
      Current equipment provides analysis for the detection of arrhythmias, ST-segment
      deviation, and more sophisticated analyses (late potentials, Q-T behavior, and
      heart-rate variability). However, despite the system used, a number of artifacts
      could mislead diagnosis. METHODS AND RESULTS: We prospectively searched for
      artifacts during ambulatory electrocardiography in patients referred for
      monitoring to our institution, a tertiary referral center. Patients were
      ambulatory at home, work, school, or within the hospital. We divided artifacts
      according to Krasnow and Bloomfield's classification (pseudoarrhythmia,
      nonarrhythmia), and we added a new category, artifacts in patients with
      pacemakers. Artifacts encountered mimicked sinus arrest, supraventricular
      arrhythmias, ventricular arrhythmias, and aberrancy. Examples of each one and
      diagnostic clues are provided to recognize these artifacts properly. CONCLUSIONS:
      A substantial amount of invalid data (false-positive findings because of
      electrocardiographic artifacts) were identified during ambulatory
      electrocardiographic monitoring that can lead to inappropriate interpretation and
      may result in severe diagnostic errors.

PMID- 12177634
TI  - Therapy for cardiovascular disease in patients with chronic kidney disease:
      appropriate caution or the absence of data.

PMID- 12177633
TI  - Assessment of diastolic function by cardiovascular magnetic resonance.
AB  - BACKGROUND: The assessment of diastolic heart function has been hampered by
      multiple difficulties. Cardiovascular magnetic resonance (CMR) is a new,
      noninvasive technique to study cardiac function. METHODS: The literature on CMR
      for the analysis of diastolic function and its clinical applications is
      extensively reviewed. RESULTS: Analysis of ventricular filling velocity and
      volume flow, volumetric assessment of ventricular chamber volume, analysis of 3
      dimensional myocardial strains, and assessment of myocardial energy content are
      numerous validated applications of CMR. With the advent of real-time imaging and
      automated analysis of myocardial strains, CMR tagging is a promising method to
      assess regional diastolic function. Today, many CMR techniques are leaving the
      experimental or developmental stage rapidly and becoming clinically available for
      the evaluation of diastolic function in heart disease. CONCLUSIONS: CMR is
      emerging as a highly accurate and reproducible noninvasive 3-dimensional
      technique for the assessment of diastolic function.

PMID- 12177635
TI  - Quality of life in patients with life-threatening arrhythmias: does choice of
      therapy make a difference?

PMID- 12177636
TI  - Assessment of clinically silent atherosclerotic disease and established and novel
      risk factors for predicting myocardial infarction and cardiac death in healthy
      middle-aged subjects: rationale and design of the Heinz Nixdorf RECALL Study.
      Risk Factors, Evaluation of Coronary Calcium and Lifestyle.
AB  - BACKGROUND: In view of consistently high cardiovascular morbidity and mortality
      rates, international efforts are aimed at developing tools for more precise risk
      prediction to allow preventive treatment targeted at high-risk individuals.
      Direct visualization of anatomic, preclinical atherosclerotic disease has the
      potential for individualized risk discrimination. Further, a variety of risk
      factors are actively evaluated, including markers of the activity of
      atherosclerotic disease, thrombogenic risk, and genetic polymorphisms. METHODS:
      The Heinz Nixdorf RECALL (Risk Factors, Evaluation of Coronary Calcium and
      Lifestyle) study is a population-based, prospective cohort study of the
      comparative value of modern risk stratification techniques for "hard" cardiac
      events. It is designed and powered to define the relative risk associated with
      the specific extent of coronary atherosclerosis measured by means of electron
      beam computed tomography (EBCT)-derived coronary calcium quantities for
      myocardial infarction and cardiac death in 5 years in 4200 males and females aged
      45 to 75 years in an unselected urban population from the large, heavily
      industrialized Ruhr area. Additionally, the predictive values of conventional
      cardiovascular risk factors, new candidate and socioeconomic risk factors,
      certain genetic polymorphisms, and direct signs of subclinical disease are
      examined with the ankle-brachial index, resting and stress electrocardiograms,
      and determination of carotid artery intima-media thickness. Prospective clinical
      risk-benefit and health economic analyses are an inherent part of the study.
      Study findings with established clinical significance are reported to the
      participants, but the EBCT findings are withheld until the conclusion of the
      study. CONCLUSIONS: The Heinz Nixdorf RECALL study will define appropriate
      methods for identifying high-risk subgroups in the general urban population who
      may derive the greatest benefit from preventive treatment.

PMID- 12177637
TI  - Treatment of depression after myocardial infarction and the effects on cardiac
      prognosis and quality of life: rationale and outline of the Myocardial INfarction
      and Depression-Intervention Trial (MIND-IT).
AB  - BACKGROUND: Patients with a depressive disorder after myocardial infarction (MI)
      have a significantly increased risk of major cardiac events. The Myocardial
      INfarction and Depression-Intervention Trial (MIND-IT) investigates whether
      antidepressive treatment can improve the cardiac prognosis for these patients.
      The rationale and outline of the study are described. METHODS: In this
      multicenter randomized clinical trial, 2140 patients admitted for MI are screened
      for depressive symptoms with a questionnaire 0, 3, 6, 9, and 12 months after MI.
      Patients with symptoms undergo a standardized psychiatric interview. Those with a
      post-MI depressive episode are randomized to intervention (ie, antidepressive
      treatment; n = 190) or care-as-usual (CAU; n = 130). In the intervention arm, the
      research diagnosis is to be confirmed by a psychiatrist. First-choice treatment
      consists of placebo-controlled treatment with mirtazapine. In case of refusal or
      nonresponse, alternative open treatment with citalopram is offered. In the CAU
      arm, the patient is not informed about the research diagnosis. Psychiatric
      treatment outside the study is recorded, but no treatment is offered. Both arms
      are followed for end points (cardiac death or hospital admission for MI, unstable
      angina, heart failure, or ventricular tachyarrhythmia) during an average period
      of 27 months. Analysis is on an intention-to-treat basis. CONCLUSION: The MIND-IT
      study will show whether treatment of post-MI depression can improve cardiac
      prognosis.

PMID- 12177638
TI  - Benefits of aspirin and beta-blockade after myocardial infarction in patients
      with chronic kidney disease.
AB  - BACKGROUND: There have been no randomized trials of cardioprotective therapy
      after acute myocardial infarction in patients with chronic kidney disease who
      should be largely eligible for aspirin (acetylsalicylic acid; ASA) and beta
      blockers (BB) as a base of therapy. METHODS: We analyzed a prospective coronary
      care unit registry of 1724 patients with ST-segment elevation myocardial
      infarction. RESULTS: Usage rates were 52.3%, 19.0%, 15.2%, and 13.5% for ASA and
      BB (ASA+BB), BB alone, ASA alone, and no ASA or BB therapy. Patients who received
      ASA+BB were more likely to be male, free of earlier cardiac disease, and
      recipients of thrombolysis. Conversely, the absence of ASA+BB was observed in
      patients with heart failure on admission, left bundle branch block, atrial and
      ventricular arrhythmias, and shock. The combination of ASA+BB was used in 63.9%,
      55.8%, 48.2%, and 35.5% of patients with corrected creatinine clearance values of
      >81.5, 81.5 to 63.1, 63.1 to 46.2, and <46.2 mL/min/72 kg (P <.0001). ASA+BB was
      used in 40.4% of patients undergoing dialysis. The age-adjusted relative risk
      reduction for the inhospital mortality rate was similar among all renal groups
      and ranged from 64.3% to 80.0% (all P <.0001). CONCLUSION: ASA+BB is an underused
      therapy in patients with acute myocardial infarction who have underlying kidney
      disease.

PMID- 12177639
TI  - C-reactive protein and incident coronary heart disease in the Atherosclerosis
      Risk In Communities (ARIC) study.
AB  - BACKGROUND: Recent evidence implicates inflammation in the pathogenesis of
      coronary heart disease (CHD). C-reactive protein, a plasma marker of
      inflammation, is a marker of CHD risk but has been studied in few prospective
      investigations of the general population. METHODS AND RESULTS: We prospectively
      examined the association of CRP with incident CHD among middle-aged adults in the
      Atherosclerosis Risk In Communities (ARIC) study. With the use of a nested case
      cohort approach, we measured CRP in stored, baseline blood samples of 2 groups of
      subjects in whom CHD developed during follow-up (242 incident cases from 1987 to
      1993 and 373 from 1990 to 1995) and, for comparison, 2 stratified random samples
      of noncases. In analyses adjusted for demographic variables and traditional CHD
      risk factors, the relative risk of CHD across quintiles of CRP was 1.0, 0.8, 1.6,
      1.9, and 1.5 for events from 1987 to 1995 (P for trend =.01). As expected,
      inclusion of fibrinogen, intracellular adhesion molecule-1, and white blood cell
      count (other potential markers of the inflammatory reaction) attenuated the
      association of CRP with CHD incidence. In a supplemental cross-sectional
      analysis, CRP was not associated with carotid intima-media thickness after
      adjustment for major risk factors. CONCLUSIONS: C-reactive protein is a
      moderately strong marker of risk of CHD in this cohort of middle-aged adults,
      consistent with the role of inflammation in the pathogenesis of CHD events. The
      association was not specific to CRP because other markers of inflammation could
      largely account for the finding.

PMID- 12177640
TI  - Cardiologists' discussions about sexuality with patients with chronic coronary
      artery disease.
AB  - BACKGROUND: Sexuality is an important factor influencing quality of life that may
      be altered for patients with coronary disease. Little is known about the extent
      to which patients want their cardiologists to counsel them about sexuality.
      PURPOSE: Our study evaluated the extent to which patients with known coronary
      disease expect cardiologists to discuss matters related to sexuality. A secondary
      goal was to determine the extent to which patients' preferences correspond to the
      realities of clinical practice. RESULTS: On the basis of the results of a
      questionnaire survey completed by 48 women and 188 men with known coronary
      disease in an outpatient cardiology practice, we found that most patients
      believed that their cardiologist should talk with them about sexual functioning.
      However, only a minority (3% men, 18% women) believed that they were adequately
      informed about their sexual functioning. Chart review demonstrated that most
      discussions occurred with male patients and that sexual dysfunction was also more
      likely to be discussed with men (43%) than with women (13%). CONCLUSIONS: Our
      study suggests that patients welcome the chance to talk with their cardiologist
      about sexual function. More attention should be given to this aspect of quality
      of life, especially for women with coronary disease.

PMID- 12177641
TI  - Development and prognosis of non-Q-wave myocardial infarction in the thrombolytic
      era.
AB  - BACKGROUND: Data on non-Q myocardial infarctions (MI) are derived primarily from
      prethrombolytic era studies. Previous trials demonstrated different development
      rates and none reported on clinical outcomes. METHODS: Our goal was to determine
      the incidence and prognosis of non-Q-wave MI among patients with ST-segment
      elevation receiving thrombolysis. A retrospective analysis of 5 randomized
      controlled trials was made. The main outcome measures included rates of (1)
      transformation of ST-segment elevation to Q- and non-Q-wave MI and (2) inhospital
      and 1-year mortality and reinfarction among patients who subsequently develop a Q
      or non-Q MI postthrombolysis as compared to controls. RESULTS: Non-Q wave
      development was greater among patients receiving thrombolysis versus
      placebo/control (3.1% absolute difference, 95% CI 1.2%-5.0%). Among patients
      receiving thrombolysis, those who developed a non-Q MI experienced significantly
      lower inhospital and 1-year mortality (absolute differences -3.8% [95% CI -5.2%
      to -2.4%] and -6.4% [95% CI -9.9% to -3.0%], respectively) and reinfarction
      (absolute differences -2.9% [95% CI -4.3% to -1.6%] and -3.5% [95% CI -6.1% to 
      0.9%], respectively) rates, compared with those who evolved a Q MI. Inhospital
      and 1-year mortality was also significantly lower when compared to
      placebo/control patients who developed a non-Q MI (absolute differences 4.6% [95%
      CI -8.2% to -1.1%] and -7.5% [95% CI -12.5% to -2.5%], respectively).
      CONCLUSIONS: Patients receiving thrombolysis more often develop a non-Q-wave MI
      and have a better prognosis than either those who develop a Q MI postthrombolysis
      or a non-Q MI after standard medical therapy.

PMID- 12177642
TI  - Nature and progression of pericardial effusion in patients with a first
      myocardial infarction: relationship to age and free wall rupture.
AB  - BACKGROUND: Left ventricular free wall rupture (FWR) usually develops within the
      first days of acute myocardial infarction (AMI) without warning, but it is
      uncertain whether a mild pericardial effusion might herald this complication.
      METHODS: A 2-dimensional echocardiogram (2DE) was performed in patients with
      first AMI with (1149) or without (324) ST-segment elevation within 2 days. A
      second 2DE was performed 2 to 4 days later in 300 patients, 100 with and 200
      without an initial mild PE (3-9 mm), and in those with initial moderate-severe PE
      (> or =10 mm) (MSPE) or who developed hypotension or died. RESULTS: The first 2DE
      showed mild PE in 177 patients and MSPE in 51 patients, whereas a late (>2 days)
      MSPE occurred in 27 with a second routine 2DE, 15 (15%) with and 12 (6%) without
      initial mild PE (P =.01). Fourteen additional patients, 5 of 77 (6%) with and 9
      of 1045 (1%) without initial PE, presented with hypotension and late MSPE (P
      <.002). Of 92 patients with MSPE, 90 had ST-segment elevation (98%), 60 had
      tamponade (65%), and 38 died of FWR or were operated on (41%). Results of
      pericardiocentesis performed in 64 patients were positive in 58, with
      hemopericardium in 57 (98%). Multivariant analysis showed mild PE on first 2DE
      and age of >60 years as the only independent predictors of late MSPE or late
      tamponade. CONCLUSIONS: Mild PE within the first 2 days in patients aged >60
      years with a first ST-segment elevation AMI is associated with an increased risk
      of late MSPE. Moreover, in this setting MSPE is most frequently associated with
      hemopericardium, and two thirds of these patients may develop tamponade/FWR.

PMID- 12177643
TI  - Changes over time in the use of aspirin in patients hospitalized with acute
      myocardial infarction (1975 to 1997): a population-based perspective.
AB  - OBJECTIVE: The purpose of this study was to examine 2 decade-long trends in the
      use of aspirin and associated outcomes in patients hospitalized with acute
      myocardial infarction. BACKGROUND: Aspirin has been shown to be beneficial in the
      secondary prevention of AMI. However, little is known about changes over time in
      the use of aspirin in patients hospitalized with AMI and associated outcomes,
      particularly from a more generalizable population-based perspective. METHODS: We
      examined trends in aspirin use and hospital and long-term outcomes in 9336
      metropolitan Worcester, Mass, residents hospitalized with validated AMI in all
      area hospitals between 1975 and 1997. RESULTS: Between 1975 and 1986, the
      hospital use of aspirin remained stable at approximately 20%. Use of aspirin
      increased markedly after this time from 49% in 1988 to 91% in 1997. Younger age,
      male sex, and a history of hypertension or stroke were associated with an
      increased likelihood of receiving aspirin. Patients with diabetes were less
      likely to receive aspirin than were patients without diabetes. Patients who
      received aspirin during hospitalization were more likely to receive beta-blockers
      and coronary interventions. Patients treated with aspirin were significantly less
      likely to have heart failure or cardiogenic shock develop or to die during
      hospitalization as compared with patients not treated with aspirin. Patients
      treated with aspirin had significantly higher survival rates over a 10-year
      follow-up period. CONCLUSION: The results of this community-wide study show that
      aspirin use in patients hospitalized with AMI has dramatically increased over
      time. Despite the beneficial effects associated with the use of aspirin, this
      therapy remains underused in several high-risk groups.

PMID- 12177644
TI  - Blunted vasodilatory responses in the cutaneous microcirculation of cigarette
      smokers.
AB  - OBJECTIVE: The present study was undertaken to investigate whether chronic
      smoking alters the vasodilatory capacity in the microcirculation. METHODS: We
      assessed, in habitual cigarette smokers, the forearm skin blood flow response to
      iontophoretically applied acetylcholine (endothelium-dependent vasodilator) and
      sodium nitroprusside. Postocclusive forearm reactive hyperemia was also explored.
      The skin blood flow responses were determined with a laser-Doppler flowmeter that
      allowed us to scan the surface after acetylcholine and sodium nitroprusside
      application. RESULTS: Forty healthy male volunteers were included. Twenty
      subjects were aged 20 to 35 years and 20 subjects were aged 40 to 60 years. We
      studied the following 4 groups of 10 subjects each: group 1, younger smokers
      (mean of 7.2 pack-years); group 2, older smokers (mean of 30 pack-years); group
      3, younger nonsmokers; and group 4, older nonsmokers. On the day of the
      experiment, the subjects of groups 1 and 2 were asked to smoke at least 15
      cigarettes from the morning until the afternoon, when the experiments were
      performed. No significant difference in the studied parameters was observed
      between younger smokers and younger nonsmokers. In older smokers, however, both
      acetylcholine- and sodium nitroprusside-induced skin blood flow increases were
      significantly attenuated in comparison with nonsmokers. Heart rate also was
      significantly blunted by long-term cigarette smoking in older subjects.
      CONCLUSION: These data show that the vasodilatory response of the skin
      microvasculature is impaired in subjects who have smoked cigarettes for many
      years. This abnormality involves both endothelium-dependent and endothelium
      independent responses.

PMID- 12177645
TI  - Coronary vasospasm as a possible cause of elevated cardiac troponin I in patients
      with acute coronary syndrome and insignificant coronary artery disease.
AB  - BACKGROUND: Abnormal levels of serum cardiac troponin I (cTnI) are occasionally
      found in patients presenting with acute coronary syndromes but having
      insignificant coronary artery disease. Before one concludes that an abnormal cTnI
      level is a false-positive result, the possibility of coronary vasospasm should be
      considered. This study investigated whether coronary vasospasm could be a reason
      for elevated cTnI in this patient population. METHODS AND RESULTS: This
      investigation enrolled 93 patients who presented to the emergency department with
      suspected coronary ischemia and had insignificant coronary artery disease. cTnI
      was elevated in 23 patients (25%) and was normal in 70 patients (75%). Coronary
      vasospasm, documented by an ergonovine provocation test, was found in 38 patients
      (41%). Patients with elevated cTnI levels, compared with those with normal cTnI,
      were older (63 +/- 13 y vs 56 +/- 14 y, P =.032), had a higher incidence of males
      (78% vs 52%, P =.049) and positive ergonovine provocation tests (74% vs 30%, P
      <.0001), and tended to have a lower incidence of hypercholesterolemia (26% vs
      48%, P =.088) and normal electrocardiograms (48% vs 70%, P =.078). Multivariate
      analysis showed that the variables independently associated with an elevated cTnI
      level included coronary vasospasm (odds ratio 2.41, 95% CI 1.48-3.18, P <.0001)
      and hypercholesterolemia (odds ratio 0.64, 95% CI 0.47-0.99, P =.049). Coronary
      vasospasm (positive ergonovine provocation test) could explain 74% of elevated
      cTnI levels in patients with insignificant coronary stenosis. CONCLUSIONS: In
      patients with acute coronary syndrome with elevated cTnI and insignificant
      coronary artery disease, the possibility of coronary vasospasm as a cause of
      elevated cTnI should be considered.

PMID- 12177646
TI  - Quality of life in the Canadian Implantable Defibrillator Study (CIDS).
AB  - BACKGROUND: The primary aim of this study was to compare quality-of-life outcome
      between patients randomized to implantable cardioverter defibrillator (ICD)
      therapy and patients randomized to amiodarone treatment in the Canadian
      Implantable Defibrillator Study (CIDS). A secondary aim was to evaluate the
      effects on quality-of-life outcomes of receiving shocks from the device. METHODS:
      Quality of life was assessed in 317 English-speaking participants by use of the
      Rand Corporation's 38-item Mental Health Inventory (MHI) and the Nottingham
      Health Profile (NHP). Assessments were done in the hospital at baseline and with
      mailed questionnaires after 2, 6, and 12 months of follow-up. Sixty-two percent
      of patients completed the follow-up assessments at 6 and 12 months. RESULTS:
      Repeated measures analysis of variance revealed significant time by treatment
      group interaction effect on total MHI and the psychological distress and
      psychological well-being sub-scales, and on 5 of the 7 NHP scales (energy,
      physical mobility, emotional reactions, sleep disturbance, and lifestyle
      impairment) (P <.05). Emotional and physical health scores were shown to improve
      significantly in the ICD group and were either unchanged (emotional health) or
      deteriorated (energy and physical mobility) in the amiodarone-treated group by
      means of post-hoc comparisons. Quality of life did not improve in the subgroup of
      patients in the ICD-treated group who received > or =5 shocks from their device.
      CONCLUSION: Quality of life is better with ICD therapy than with amiodarone
      therapy. The beneficial quality-of-life effects from an ICD are not evident in
      patients who receive numerous shocks from their device.

PMID- 12177647
TI  - A multicenter study of the coding accuracy of hospital discharge administrative
      data for patients admitted to cardiac care units in Ontario.
AB  - BACKGROUND: Cardiac health services researchers frequently use cohorts derived
      from administrative hospital discharge abstract data to study the outcomes and
      treatment of coronary artery disease. However, relatively limited data exist on
      the accuracy of the coding of cardiac diagnoses in discharge abstract data. The
      goal of this study was to examine the accuracy of the coding of acute myocardial
      infarction and other cardiac diagnoses in the Canadian Institute of Health
      Information hospital discharge abstracts. METHODS: Patients admitted to 58
      cardiac care units (CCUs) in Ontario that participated in the Fastrak II Acute
      Coronary Syndromes registry were linked to CIHI hospital discharge abstracts. The
      most responsible diagnosis at hospital discharge in the administrative data was
      compared with the CCU discharge diagnosis in the clinical registry. RESULTS: A
      total of 58,816 CCU patients were linked to hospital discharge abstract data. The
      specificity, sensitivity, and positive predictive value of a most responsible
      diagnosis of acute myocardial infarction were 92.8%, 88.8%, and 88.5%,
      respectively. The specificity of CIHI diagnosis codes for arrhythmia, congestive
      heart failure, unstable angina, and chest pain not yet diagnosed were all at
      least 93.9%. However, the sensitivity of these CIHI diagnosis codes was no
      greater than 60.7%. Furthermore, the positive predictive values were no larger
      than 80.8%. CONCLUSION: Myocardial infarction is generally accurately coded in
      Ontario hospital discharge abstract data. However, other cardiac diagnoses are
      less reliably coded in discharge abstract data.

PMID- 12177648
TI  - Role of target vessel size and body surface area on outcomes after percutaneous
      coronary interventions in women.
AB  - BACKGROUND: Women have higher mortality rates than men after coronary
      angioplasty. Differences in target vessel size may partially account for these
      differences. We set out to explore the effects of sex, body surface area (BSA),
      and target coronary vessel size on clinical outcomes after angioplasty. METHODS:
      Data from 5 interventional trials and 1 registry were pooled for analysis (n =
      3982). RESULTS: Compared with men, women undergoing angioplasty were older, had
      lower weights and BSA, more coronary risk factors, and slightly smaller target
      coronary vessel size (as assessed by reference vessel diameter). The correlation
      between target vessel size and BSA was poor (r = 0.13). At 6 months, women had
      higher mortality rates (1.7% vs 0.8%, P =.03) but similar rates of myocardial
      infarction and repeat revascularization. On univariate analysis, advanced age,
      smaller BSA, and female sex were associated with increased mortality, but target
      vessel size was not. Advanced age was the only significant multivariate predictor
      of mortality. Target vessel size and diabetes were independent predictors of
      repeat revascularization. CONCLUSIONS: Women have higher unadjusted 6-month
      mortality rates after angioplasty, owing largely to their more advanced age at
      the time of intervention. Smaller target vessel size is associated with increased
      risk of restenosis and repeat revascularization; however, it does not appear to
      be a predictor for downstream mortality. As such, the fact that women have
      smaller vessels does not account for their higher 6-month mortality after
      coronary angioplasty.

PMID- 12177649
TI  - Randomized comparison of cilostazol versus ticlopidine hydrochloride for
      antiplatelet therapy after coronary stent implantation for prevention of late
      restenosis.
AB  - BACKGROUND: Cilostazol is a newly developed antiplatelet drug that has been
      widely applied for clinical use. Its antiplatelet action appears to be mainly
      related to inhibition of intracellular phosphodiesterase activity. Recently,
      cilostazol has been used for antiplatelet therapy after coronary stent
      implantation. However, its evaluation has not been established yet. METHODS: This
      prospective randomized trial was designed to investigate the efficacy of
      cilostazol for the prevention of late restenosis and acute or subacute stent
      thrombosis in comparison with ticlopidine hydrochloride. One hundred thirty
      consecutive patients, scheduled for elective coronary stenting, were randomly
      assigned to receive oral aspirin (81 mg/day) plus ticlopidine hydrochloride
      therapy (200 mg/day; group I) or aspirin plus cilostazol therapy (200 mg/day;
      group II). These medications were started at least 2 days before coronary
      intervention and continued until follow-up coronary angiography was performed 6
      months later. RESULTS: Subacute stent thrombosis was observed in 2 patients of
      group I but in no patients of group II. Major cardiac events were similarly
      present in both groups. Elevated transaminase levels were observed more
      frequently in group I than in group II (P <.05). Each of the quantitative
      coronary angiography variables before and immediately after coronary stenting
      were similar in both groups. At follow-up angiography, however, late lumen loss
      (0.69 +/- 0.79 mm vs 0.28 +/- 0.40 mm; P <.01) and loss index (0.42 +/- 0.56 vs
      0.16 +/- 0.27; P <.01) were smaller in group II than in group I. Restenosis rate
      (13% vs 31%; P <.05) and target lesion revascularization rate (7% vs 21%; P <.05)
      were both lower in group II than in group I. CONCLUSION: Aspirin plus cilostazol
      therapy may be an effective regimen for prevention of not only stent thrombosis
      but also restenosis.

PMID- 12177650
TI  - Short-term outcomes after percutaneous coronary intervention: effects of stenting
      and institutional volume shifts.
AB  - BACKGROUND: This study examines how the dissemination of stenting and procedural
      shifts to high-volume facilities have affected short-term outcomes after
      percutaneous coronary intervention (PCI). METHODS: Discharge information from the
      1994 and 1997 US Nationwide Inpatient Sample was used. Data from 1994 involved
      84,036 angioplasties, 27.3% of which were performed for acute myocardial
      infarction (AMI), at a time when stents were generally unavailable. Data from
      1997 included 118,548 angioplasties, 30.2% of which were performed for AMI and
      59% of which involved stenting. Outcomes included same-admission mortality and
      same-admission bypass grafting surgery (CABG). RESULTS: Compared with 1994, in
      1997 stents were in widespread use, and there was a significant shift in PCI
      procedures to high-volume facilities. There was no significant difference in
      overall mortality rates between 1994 and 1997. However, same-admission CABG rates
      were lower in 1997 than in 1994 for the AMI group (2.9% vs 4.7%, P <.0001) and
      for the no-AMI group (1.8% vs 3.0%, P <.0001), which was attributable almost
      entirely to stenting. For 1997 only, patients receiving stents had a lower
      mortality rate than patients undergoing PCI without stenting (AMI 2.7% vs 4.7%, P
      <.0001, no AMI 0.7% vs 0.9%, P =.004). CONCLUSIONS: Despite the dissemination of
      stenting and shifts to high-volume facilities, overall mortality rates after PCI
      have not significantly changed. However, patients undergoing stenting in 1997 had
      a significantly lower mortality rate than patients who did not undergo stenting,
      suggesting that stents may prevent inhospital deaths. Furthermore, same-admission
      CABG rates have decreased dramatically, an association seen with the introduction
      of stenting, but not with volume shifts.

PMID- 12177652
TI  - Impact of deep vessel wall injury and vessel stretching on subsequent arterial
      remodeling after balloon angioplasty: a serial intravascular ultrasound study.
AB  - BACKGROUND: Arterial remodeling has been shown to be responsible for lumen
      narrowing after nonstent interventions. METHODS: To examine the impact of deep
      vessel wall injury (DI) after balloon angioplasty on the subsequent vessel
      remodeling process, we performed serial intravascular ultrasound (IVUS) analysis
      in 47 native coronary artery lesions that underwent balloon angioplasty. An IVUS
      study was performed before and after balloon angioplasty and repeated at follow
      up. Vessel and lumen area were measured at the narrowest site before
      intervention. Plaque area was calculated as vessel area minus lumen area. DI was
      defined as the presence of plaque/vessel wall fracture deep in the medial layer
      (sonolucent zone by IVUS) after angioplasty. RESULTS: After angioplasty, DI was
      present in 18 (38%, DI group) and absent in 29 (62%, non-DI group) of lesions.
      During follow-up, changes in vessel area in the DI group were significantly
      larger than in the non-DI group (P =.007). There were no significant differences
      in changes in plaque area. A trend toward greater late lumen loss was observed in
      the non-DI group (P =.05). In the DI group, changes in lumen area correlated
      better with changes in vessel area (r = 0.81, P <.0001) than with changes in
      plaque area (r = 0.32, P =.20). However, in the non-DI group, changes in lumen
      area correlated with changes in plaque area (r = -0.55, P =.002), but not with
      changes in vessel area (r = 0.30, P =.11). CONCLUSIONS: Deep vessel wall injury
      after balloon angioplasty is associated with the magnitude of the subsequent
      vessel remodeling process. The differences in the remodeling process may have
      implications regarding adjunctive therapies to prevent restenosis after balloon
      angioplasty.

PMID- 12177651
TI  - Abciximab therapy improves 1-month survival rate in unselected patients with
      acute myocardial infarction undergoing routine infarct artery stent implantation.
AB  - BACKGROUND: The impact of abciximab therapy on mortality in unselected patients
      with acute myocardial infarction (AMI) undergoing routine primary infarct-related
      artery (IRA) stent implantation is not yet defined, and previous randomized
      studies have produced conflicting results. METHODS: A strategy of IRA stenting
      alone as opposed to IRA stenting plus abciximab was compared in a series of 561
      consecutive unselected patients with AMI. Abciximab treatment was strongly
      encouraged for all patients. The contraindication for abciximab therapy was a
      high risk of major bleeding as assessed by the operator before mechanical
      intervention. RESULTS: Of 561 patients, 348 patients underwent abciximab therapy
      and 213 underwent primary IRA stenting alone. The 1-month overall mortality rate
      was 2.9% in the abciximab group and 10.8% in the stent alone group (P <.001). The
      relative reduction in mortality rate was 73% for patients overall, 77% in the
      subset of patients aged < or =70 years (mortality rate, 1.2% vs 5.2%, P =.020),
      57% in patients aged >70 years (7.7% vs 18%, P =.043), 63% in patients with
      cardiogenic shock (17% vs 46%, P =.022), and 77% in patients without cardiogenic
      shock (1.3% vs 5.6%, P =.002). Multivariate analyses on the basis of all
      patients, and on the subset of patients aged < or =70 years, showed that
      abciximab therapy was independently related to the risk of death at 1 month. No
      differences were seen between groups in the procedural success rate (99.1% vs
      98.1%) or in the incidence rates of nonfatal reinfarction (0.3% vs 1.9%) or
      repeat target vessel revascularization (1.7% vs 1.9%). CONCLUSION: The results of
      this study strongly support the use of abciximab therapy in nonselected patients
      with AMI undergoing routine IRA stent implantation. The mechanism of the clinical
      benefit of abciximab was not related to the patency of the IRA.

PMID- 12177653
TI  - Quantification of valvular aortic stenosis by magnetic resonance imaging.
AB  - BACKGROUND: Assessing the aortic valvular orifice is important in judging the
      severity of aortic stenosis. Magnetic resonance imaging visualizes in-plane
      valvular motion. We studied the value of magnetic resonance planimetry of the
      aortic valve orifice. METHODS: We used breath-hold gradient echocardiographic
      sequences on a clinical magnetic resonance system (1.5 T) and studied 25 patients
      with symptomatic valvular aortic stenosis. We performed a planimetry of the
      valvular orifice in systolic images of the valvular plane. The results were
      compared with echocardiography (continuity equation) and cardiac catheterization
      (Gorlin formula). RESULTS: Magnetic resonance planimetry was feasible in all
      patients, and the image quality was invariably adequate. The magnetic resonance
      imaging results correlated well with the data calculated from catheterization and
      less robustly with the echocardiographic results. The 3 methods were similar in
      terms of leading to clinical decisions. CONCLUSIONS: We suggest that magnetic
      resonance flow planimetry of the aortic valve orifice offers a simple, reliable,
      fast, and safe method to noninvasively quantify aortic stenosis.

PMID- 12177654
TI  - Significance of ST-segment morphology noted on electrocardiography during the
      recovery phase after exercise in patients with ischemic heart disease as analyzed
      with simultaneous dual-isotope single photon emission tomography.
AB  - BACKGROUND: The significance of differences in electrocardiographic morphology
      that occur during the recovery phase after exercise has not been clarified. We
      investigated the relationship between postexercise electrocardiographic
      morphology and the pattern of residual ischemia measured at that time. METHODS:
      Exercise dual-isotope single photon emission computed tomography was performed on
      171 consecutive patients with chest pain syndrome. After injection of technetium
      99m tetrofosmin at peak exercise and thallium-201 at 3 minutes after exercise,
      dual-isotope single photon emission computed tomographic images were obtained
      simultaneously. After cross-talk compensation, the extent of ischemia and its
      localization were measured at both peak exercise and after exercise. RESULTS:
      When 64 patients with angiographically and scintigraphically proven ischemic
      heart disease were grouped by morphology of ST-segment depressions at 3 minutes
      after exercise, 38 patients with the downsloping type had ischemia localized
      mainly to the middle and basal levels as compared with the more rapid resolution
      of ischemia in 12 patients with horizontal type and 14 patients with no ischemic
      electrocardiographic response (apical level 18.4% [7/38], 8.3% [1/12], and 0%
      [0/14], P = not significant, middle level 47.4% [18/38], 16.7% [2/12], and 7.1%
      [1/14], P <.01, basal level 57.9% [22/38], 33.3% [4/12], and 14.3% [2/14], P
      <.02, respectively) independent of the extent or localization of any ischemia
      noted during exercise (all levels, P = not significant). CONCLUSION:
      Electrocardiographic morphology during the recovery phase of exercise reflects
      the extent and localization of residual ischemia at that time independent of
      ischemic changes noted during exercise.

PMID- 12177655
TI  - Echocardiography-derived variables predict outcome in patients with nonischemic
      dilated cardiomyopathy with or without a restrictive filling pattern.
AB  - BACKGROUND: Despite recent therapeutic advances, patients with heart failure
      caused by dilated cardiomyopathy (DCM) still have high morbidity and mortality
      rates. In this study, we sought to assess the prognostic value of
      echocardiographic variables in patients with DCM and to assess the impact of a
      restrictive left ventricle filling pattern. DESIGN: We conducted a retrospective
      cohort study of 337 patients with DCM, using the Royal Brompton Hospital
      Echocardiography database for the years 1994 to 1998. METHODS AND RESULTS: There
      were 337 patients with a mean age of 53 +/- 15 years. One hundred ninety-five
      patients (58%) had a restrictive left ventricle filling pattern (RFP). There was
      a total of 74 deaths (22%) during the follow-up period (43 +/- 25 months). RFP
      more than tripled the risk of death (adjusted hazard ratio 3.2, 95% CI 1.8-5.7, P
      =.003). RFP is correlated with isovolumic relaxation time, incoordinate wall
      motion, amplitude of right ventricular long axis excursion on M-mode
      echocardiography, and mitral regurgitation. CONCLUSION: RFP is a powerful
      independent predictor of mortality in patients with nonischemic DCM. The risk
      associated with RFP is greatest among patients who had short isovolumic
      relaxation time, mitral regurgitation, incoordinate wall-motion, and depressed
      amplitude of right ventricular long axis excursion. Thus, echocardiography
      derived variables may stratify patients with heart failure with DCM who are at
      high risk, for whom aggressive medical treatment or heart transplantation should
      be considered early.

PMID- 12177656
TI  - Cardiac troponin I: a potential marker of exercise intolerance in patients with
      moderate heart failure.
AB  - BACKGROUND: In severe heart failure, increased values of cardiac troponins have
      been detected during decompensation. In this study, we investigated whether an
      increase of cardiac troponin I can be observed after symptom-limited exercise and
      after an exercise training session in patients with moderate heart failure.
      METHODS: Twenty-seven patients with moderate heart failure (New York Heart
      Association II-III, ejection fraction 31% +/- 8%) were compared with 9 patients
      with mild heart failure and 10 subjects without heart failure. They underwent a
      symptom-limited exercise test and a bicycle exercise training session at >80% of
      maximal heart rate over 20 to 30 minutes. Plasma cTnI levels were measured at
      baseline, after symptom-limited exercise (hourly for 5 hours), and after training
      (4 and 10 hours). RESULTS: Patients with moderate heart failure showed an
      increase of cTnI from 37 +/- 49 pg/mL to 73 +/- 59 pg/mL (P <.001) after symptom
      limited exercise. Four patients with moderate and 1 with mild heart failure and
      normal cTnI values at rest showed an increase of cTnI above 100 pg/mL after acute
      exercise but not after training. Subjects without heart failure had lower cTnI
      levels at rest and significantly lower values after symptom-limited exercise and
      training (P <.05 for each). CONCLUSION: Patients with symptomatic heart failure
      reveal an increase of cTnI after symptom-limited exercise at levels that indicate
      minor myocardial damage. The prognostic impact of this finding should, therefore,
      be further investigated.

PMID- 12177657
TI  - Growth hormone administration reduces circulating proinflammatory cytokines and
      soluble Fas/soluble Fas ligand system in patients with chronic heart failure
      secondary to idiopathic dilated cardiomyopathy.
AB  - BACKGROUND: Recent studies have shown that an abnormal proinflammatory cytokine
      expression and apoptotic process contribute to adverse left ventricular
      remodeling and progress of chronic heart failure. This study investigates the
      effects of growth hormone (GH) administration on serum levels of representative
      proinflammatory cytokines and soluble apoptosis mediators in patients with
      chronic heart failure secondary to idiopathic dilated cardiomyopathy (IDC).
      METHODS: Serum levels of tumor necrosis factor-alpha (TNF-alpha), its soluble
      receptors (sTNF-RI, sTNF-RII), interleukin-6 (IL-6), soluble IL-6 receptor (sIL
      6R), soluble Fas (sFas) and soluble Fas Ligand (sFasL) were determined (enzyme
      linked immunosorbent assay method) in 10 patients with IDC (New York Heart
      Association class III, ejection fraction 24% +/- 2%) before and after a 3-month
      subcutaneous administration of 4 IU GH every other day (randomized crossover
      design). Peak oxygen consumption (Vo(2)max) was also used to evaluate the
      functional status of patients with IDC. RESULTS: Treatment with GH produced a
      significant reduction in serum levels of TNF-alpha (8.2 +/- 1.2 vs 5.7 +/- 1.1
      pg/mL, P <.05), sTNF-RI (3.9 +/- 0.4 vs 3.2 +/- 0.3 ng/mL, P <.05), sTNF-RII (2.6
      +/- 0.3 vs 2.2 +/- 0.2 ng/mL, P <.05), IL-6 (5.5 +/- 0.6 vs 4.4 +/- 0.4 pg/mL, P
      =.05), sIL-6R (32.7 +/- 3.0 vs 28.2 +/- 3.0 ng/mL, P <.05), sFas (4.4 +/- 0.8 vs
      3.1 +/- 0.6 ng/mL, P <.05), and sFasL (34.2 +/- 11.7 vs 18.8 +/- 7.3 pg/mL, P
      <.01). A significant improvement was also observed in VO2max after the completion
      of 3 months' treatment with GH (15.0 +/- 0.8 vs 17.2 +/- 1.0 mL/kg/min, P <.05).
      Good correlations were found between GH-induced reduction in TNF-alpha levels and
      increase in VO2max (r = -0.64, P <.05) as well as between GH-induced reduction in
      sFasL and increase in VO2max (r = -0.56, P =.08). CONCLUSIONS: GH administration
      reduces serum levels of proinflammatory cytokines and soluble Fas/FasL system in
      patients with IDC. These immunomodulatory effects may be associated with
      improvement in clinical performance and exercise capacity of patients with IDC.

PMID- 12177658
TI  - Correlates and outcomes of preserved left ventricular systolic function among
      older adults hospitalized with heart failure.
AB  - BACKGROUND: Heart failure (HF) in older adults is often associated with preserved
      left ventricular systolic function (LVSF). The objective of this retrospective
      follow-up study was to determine the correlates and outcomes of preserved LVSF
      among older adults hospitalized with HF. METHODS: We studied older Medicare
      beneficiaries hospitalized with HF (n = 1091) who had documented LVSF evaluation
      (n = 438). LVSF was defined as preserved if left ventricular ejection fraction
      was > or =40%. The Fisher exact test and the Student t test were used to compare
      baseline characteristics between patients with preserved versus those with
      impaired LVSF. Multivariate logistic regression analysis was used to determine
      the correlates of preserved LVSF. Cox proportional hazards analyses were used to
      determine the associations between LVSF and both 4-year mortality rates and 6
      month readmission rates and the associations between angiotensin-converting
      enzyme (ACE) inhibitor use and 4-year mortality rates, separately, in patients
      with preserved and impaired LVSF. RESULTS: Of the 438 patients, 200 (46%) had
      preserved LVSF. Women were more likely to have preserved LVSF (odds ratio [OR] =
      2.44, 95% CI 1.57-3.81) than men. Preserved LVSF was associated with lower 4-year
      mortality rates (adjusted hazards ratio [HR] = 0.67, 95% CI 0.52-0.86) but not
      with 6-month readmission rates (adjusted HR = 0.66, 95% CI 0.41-1.09). The use of
      ACE inhibitors was associated with lower 4-year mortality rates in patients with
      impaired LVSF (adjusted HR = 0.61, 95% CI 0.43-0.86) but not in those with
      preserved LVSF (HR = 0.96, 95% CI 0.65-1.42). CONCLUSIONS: Among older adults
      hospitalized with HF, preserved LVSF was common among women and was associated
      with significantly higher morbidity and mortality rates, which were unaffected by
      treatment with ACE inhibitors.

PMID- 12177659
TI  - Effectiveness of a novel serotonin blocker, sarpogrelate, for patients with
      angina pectoris.
AB  - BACKGROUND: We have recently demonstrated that a single oral administration of
      sarpogrelate, a 5-HT(2A) receptor antagonist, may improve exercise capacity in
      anginal patients with well-developed collaterals. The aim of the current study
      was to investigate the effectiveness of 2-week treatment with sarpogrelate on
      anginal symptoms and exercise capacity in anginal patients. METHODS: A treadmill
      exercise test was repeated after a 2-week period with or without sarpogrelate
      (100 mg 3 times a day) in 20 patients with angiographically proven stable angina.
      Anginal symptoms and daily physical activity by the specific activity scale (SAS)
      were also evaluated. RESULTS: Treatment with sarpogrelate significantly increased
      the SAS score and prolonged exercise time to the onset of 0.1-mV ST depression.
      When data were analyzed in a subgroup of patients (n = 8) with well-developed
      collaterals, the treatment with sarpogrelate decreased the number of anginal
      attacks (control vs sarpogrelate, 3.0 +/- 2.8 vs 0.9 +/- 1.1/2 weeks, P <.05),
      increased the SAS score (5.2 +/- 1.6 vs 6.2 +/- 1.3 METS, P <.05), and increased
      the time to the onset of 0.1-mV ST depression (235 +/- 84 vs 295 +/- 127 seconds,
      P <.05). In addition, the double product at the onset of 0.1-mV ST depression
      increased by 15% (P <.05) after sarpogrelate. In contrast, all parameters were
      not significantly changed after sarpogrelate treatment in patients (n = 12)
      without well-developed collaterals. CONCLUSIONS: These findings indicate the
      therapeutic effectiveness of sarpogrelate for anginal patients, especially for
      patients with well-developed collaterals.

PMID- 12177660
TI  - An integrated approach to diagnosis and therapeutic management of patients with
      systolic heart failure in the Copenhagen metropolitan area.
AB  - BACKGROUND: Studies on the effect of heart failure clinics have been encouraging
      and convincing with respect to reduced hospitalizations, improved quality of
      life, and reduced cost. However, previous results have been derived from patient
      populations either recently discharged and with specific exclusion criteria or
      from heart transplant lists. We here report the establishment of a heart failure
      clinic that offers an integrated approach to both diagnosing and managing heart
      failure patients, the baseline characteristics of the first 283 patients treated,
      and the impact on heart failure hospitalizations during establishment. METHODS:
      Since September l, 1999, a heart failure clinic has been in operation at
      Frederiksberg University Hospital. The clinic was designed with both a diagnostic
      and a therapeutic unit. The diagnostic unit offers open access to all patients
      with suspected heart failure, either through referral from general practitioners
      or from the medical departments of the hospital. In the case of confirmed
      systolic heart failure, the patient is referred to the therapeutic unit for (1)
      uptitration and optimization of medical therapy and thorough information and
      education. In addition, the unit offers a rapid access track and the possibility
      of intravenous diuretic treatment. RESULTS: During the 21 months of operation, a
      total of 460 patients were referred to the clinic. Of these, 320 (70%) were found
      to have clinical evidence of heart failure, and 283 (88% of the patients with
      heart failure) had left ventricular systolic dysfunction (defined by an ejection
      fraction of < or =45%). These patients were seen in the clinic for education,
      control of fluid retention, and uptitration of medications. These patients with
      left ventricular dysfunction were predominantly elderly (aged 72.7 +/- 10.7 y)
      and most often male (73%). Ischemic heart disease was the most common etiology
      (55%). Before referral, most patients with left ventricular dysfunction had been
      treated with none or only low-dose angiotensin-converting enzyme inhibitor (55%),
      and fewer than one third received beta-blockers (29%). During the first year of
      operation of the clinic, there was a 23% decline of heart failure-related
      hospital admissions to the department of cardiology (from 396 to 306).
      CONCLUSIONS: Patients with systolic heart failure are not always optimally
      treated. The establishment of a heart failure clinic, which offers the
      combination of diagnosing and managing congestive heart failure, appears to be
      efficient both in terms of therapy optimization and with respect to a concomitant
      decline in hospitalization for heart failure.

PMID- 12177662
TI  - Tackling malignant hypertension: not so desperate now.

PMID- 12177661
TI  - Beneficial effects of metoprolol on myocardial sympathetic function: Evidence
      from a randomized, placebo-controlled study in patients with congestive heart
      failure.
AB  - BACKGROUND: We sought to investigate whether beta-blockers exert a presynaptic
      effect in the myocardium as measured by 123I-metaiodobenzylguanidine. METHODS:
      The study comprised 59 patients with congestive heart failure, New York Heart
      Association class II or III, and left ventricular ejection fraction <35%. After
      an open label titration phase, patients were randomized to their maximal
      tolerable dose of metoprolol or placebo. Myocardial MIBG uptake was measured
      before the titration phase and after 6 months of treatment. Other parameters were
      maximal oxygen consumption, 6-minute walking test, plasma neurohormones, and
      echocardiographic parameters. RESULTS: We found a 21.9% increase in mean
      myocardial MIBG uptake after 6 months of treatment with metoprolol. In contrast,
      MIBG uptake decreased by 7.8% in the placebo group (P = 0.03 compared with
      metoprolol). Left ventricular end-diastolic diameter decreased from 74 +/- 11 mm
      to 67 +/- 10 mm (P <.05, within-group comparison) and LVEF increased from 25.3%
      +/- 7.4% to 32.6% +/- 9.6% (P <.05, within-group comparison) in the metoprolol
      group. Placebo-treated patients showed no significant changes. Comparison of
      changes in left ventricular end-diastolic diameter and LVEF between metoprolol
      and placebo did not reach statistical significance (P = 0.2). CONCLUSIONS: This
      randomized, placebo-controlled study demonstrates that metoprolol has a
      presynaptic effect as measured by myocardial MIBG scintigraphy in both ischemic
      and nonischemic cardiomyopathy.

PMID- 12177665
TI  - Case of the month: Culture shock.

PMID- 12177667
TI  - Under the influence. Mix one part EMS with one part intoxicated patient, add a
      twist--a fall, an MVA--& you've got anything but a routine call.

PMID- 12177668
TI  - Best practices in injury prevention: national award highlights programs across
      the nation.

PMID- 12177669
TI  - I wish I had a camera: legal & ethical implications of EMS photography.

PMID- 12177670
TI  - Acute coronary syndromes: the prehospital assessment & management of cardiac
      related chest pain.

PMID- 12177684
TI  - Pharmacology of flibanserin.
AB  - Flibanserin has preferential affinity for serotonin 5-HT(1A), dopamine D(4k), and
      serotonin 5-HT(2A) receptors. In vitro and in microiontophoresis, flibanserin
      behaves as a 5-HT(1A) agonist, a very weak partial agonist on dopamine D(4)
      receptors, and a 5-HT(2A) antagonist. In vivo flibanserin binds equally to 5
      HT(1A) and 5-HT(2A) receptors. However, under higher levels of brain 5-HT (i.e.,
      under stress), flibanserin may occupy 5-HT(2A) receptors in higher proportion
      than 5-HT(1A) receptors. The effects of flibanserin on adenylyl cyclase are
      different from those of buspirone and 8-OH-DPAT, two other purported 5-HT(1A)
      receptor agonists. Flibanserin reduces neuronal firing rate in cells of the
      dorsal raphe, hippocampus, and cortex with the CA1 region being the most
      sensitive in the brain. Flibanserin-induced reduction in firing rate in the
      cortex seems to be mediated through stimulation of postsynaptic 5-HT(1A)
      receptors, whereas the reduction of the number of active cells seems to be
      mediated through dopamine D(4) receptor stimulation. Flibanserin quickly
      desensitizes somatic 5-HT autoreceptors in the dorsal raphe and enhances tonic
      activation of postsynaptic 5-HT(1A) receptors in the CA3 region. Flibanserin
      preferentially reduces synthesis and extracellular levels of 5-HT in the cortex,
      where it enhances extracellular levels of NE and DA. Flibanserin displays
      antidepressant-like activity in most animal models sensitive to antidepressants.
      Such activity, however, seems qualitatively different from that exerted by other
      antidepressants. Flibanserin seems to act via direct or indirect stimulation of 5
      HT(1A), DA, and opioid receptors in those animal models. Flibanserin does not
      display consistent effects in animal models of anxiety and seems to exert
      potential antipsychotic effects. Flibanserin may induce some sedation but does
      not induce observable toxic effects at pharmacologically relevant doses.

PMID- 12177685
TI  - Ensaculin (KA-672 HCl): a multitransmitter approach to dementia treatment.
AB  - Ensaculin, a novel benzopyranone substituted with a piperazine moiety, showed
      memory-enhancing effects in paradigms of passive and conditioned avoidance in
      both normal and artificially amnesic rodents. It exhibited neuroprotective
      activities in an NMDA toxicity model and neurotrophic effects in primary cultured
      rat brain cells. The compound could be characterized as a weak NMDA receptor
      operated channel blocker. In receptor-binding studies, ensaculin was found to
      have high affinities to serotonergic 5-HT(1A) and 5-HT(7) receptors, adrenergic
      alpha(1), and dopaminergic D(2) and D(3) receptors. Due to its unique
      pharmacodynamic profile, ensaculin may have potential as an antidementia agent
      acting on various transmitter systems.

PMID- 12177686
TI  - Galantamine--a novel cholinergic drug with a unique dual mode of action for the
      treatment of patients with Alzheimer's disease.
AB  - Galantamine hydrobromide is a tertiary alkaloid drug that has been developed and
      approved in a number of countries including the USA and several countries in
      Europe as a treatment for mild-to-moderate Alzheimer's disease (AD). Galantamine
      has a unique, dual mode of action. It is a reversible, competitive inhibitor of
      acetylcholinesterase (AChE), and is the only drug actively marketed for the
      treatment of AD with proven activity as an allosteric modulator of nicotinic
      acetylcholine receptors (nAChRs). This latter activity is thought to be
      particularly important since decreases in the expression and activity of nAChRs
      make a large contribution to the reduction in central cholinergic
      neurotransmission in patients with AD. Galantamine exhibits favorable
      pharmacokinetic characteristics including predictable linear elimination kinetics
      at the recommended maintenance doses (16 and 24 mg/day), a relatively short half
      life (approximately 7 h) and high bioavailability. It is extensively metabolized
      in numerous pathways, mainly in the liver via cytochrome P450 enzymes CYP2D6 and
      CYP3A4, and has a low potential for clinically significant drug-drug
      interactions. During four large randomized, double-blind, placebo-controlled
      trials of up to 6 months duration, galantamine 16 and 24 mg/day significantly
      benefited cognitive and global function, ability to perform activities of daily
      living (ADL) and behavior, relative to placebo and baseline, for up to 6 months.
      Caregiver burden (time spent by caregivers supervising patients or assisting them
      with ADL), and caregiver distress (related to patients' behavioral symptoms) were
      also reduced. Cognitive and functional abilities were preserved at or near
      baseline for at least 12 months in patients who received galantamine 24 mg/day
      for 12 months in a long-term US study. These benefits were maximized by early and
      continued galantamine treatment and, again, were associated with significant
      reductions in caregiver burden. Trials of the efficacy of galantamine in dementia
      related to cerebrovascular disease have also yielded positive results. There are
      no safety concerns associated with the use of galantamine. The incidence of
      adverse events, particularly cholinergically mediated events affecting the
      gastrointestinal system, is generally low and can be minimized using the
      recommended slow dose-escalation scheme. Galantamine may, therefore, help to
      reduce the overall burden and cost involved in caring for dementia patients.
      Taking all evidence into account, galantamine has the potential to become a first
      line therapy for dementia.

PMID- 12177687
TI  - RX 821002 as a tool for physiological investigation of alpha(2)-adrenoceptors.
AB  - RX 821002 is the 2-methoxy congener of idazoxan. In binding and tissue studies it
      behaves as a selective antagonist of alpha(2)-adrenoceptors, with at least 5
      times greater affinity for these receptors than any other binding site. It does
      not select between the different types of alpha(2)-receptor. Although this drug
      probably has no future as a therapeutic agent, it remains a good probe for
      physiological activity at alpha(2)-adrenoceptors in animal experiments. A
      particularly useful feature of this compound is its lack of binding at I(1) and
      I(2) imidazoline receptors. However, it has relatively high affinity for 5-HT(1A)
      receptors (at which it acts as an antagonist) and a tendency to behave as an
      inverse agonist at alpha(2A)-adrenoceptors in some cell culture systems. These
      potential drawbacks may be overcome by careful design of experiments, and the
      greater selectivity of RX 821002 renders it much superior to yohimbine or
      idazoxan as a tool for probing physiological actions at alpha(2)-receptors. It
      can be compared favorably with other selective antagonists such as atipamezole.
      In physiological studies, RX 821002 augments norepinephrine release in the
      frontal cortex and increases drinking behavior in rat. In rabbit, intrathecal
      administration of this drug enhances somatic and autonomic motor outflows,
      showing that tonic adrenergic descending inhibition of withdrawal reflexes and
      sympathetic pre-ganglionic neurons is strong in this species. The potentiation of
      reflexes may be considered a pro-nociceptive action. In the same model, RX 821002
      antagonizes the inhibitory effects of the mu opioid fentanyl, indicating that
      exogenous opioids synergize with endogenously released norepinephrine in the
      spinal cord. Thus, the careful use of RX 821002 has revealed several aspects of
      the physiological activity of alpha(2)-adrenoceptors in rabbit spinal cord and
      rat brain. We recommend that RX 821002 and/or compounds with similar selectivity
      for alpha(2)-adrenoceptors (atipamezole, MK-912, RS-79948) should be used in
      preference to yohimbine or idazoxan in all future studies of this type.

PMID- 12177688
TI  - Protection of the cardiovascular system by imidapril, a versatile angiotensin
      converting enzyme inhibitor.
AB  - Imidapril hydrochloride (imidapril) is a long-acting, non-sulfhydryl angiotensin
      converting enzyme (ACE) inhibitor, which has been used clinically in the
      treatment of hypertension, chronic congestive heart failure (CHF), acute
      myocardial infarction (AMI), and diabetic nephropathy. It has the unique
      advantage over other ACE inhibitors in causing a lower incidence of dry cough.
      After oral administration, imidapril is rapidly converted in the liver to its
      active metabolite imidaprilat. The plasma levels of imidaprilat gradually
      increase in proportion to the dose, and decline slowly. The time to reach the
      maximum plasma concentration (T(max)) is 2.0 h for imidapril and 9.3 h for
      imidaprilat. The elimination half-lives (t(1/2)) of imidapril and imidaprilat is
      1.7 and 14.8 h, respectively. Imidapril and its metabolites are excreted chiefly
      in the urine. As an ACE inhibitor, imidaprilat is as potent as enalaprilat, an
      active metabolite of enalapril, and about twice as potent as captopril. In
      patients with hypertension, blood pressure was still decreased at 24 h after
      imidapril administration. The antihypertensive effect of imidapril was dose
      dependent. The maximal reduction of blood pressure and plasma ACE was achieved
      with imidapril, 10 mg once daily, and the additional effect was not prominent
      with higher doses. When administered to patients with AMI, imidapril improved
      left ventricular ejection fraction and reduced plasma brain natriuretic peptide
      (BNP) levels. In patients with mild-to-moderate CHF [New York Heart Association
      (NYHA) functional class II-III], imidapril increased exercise time and physical
      working capacity and decreased plasma atrial natriuretic peptide (ANP) and BNP
      levels in a dose-related manner. In patients with diabetic nephropathy, imidapril
      decreased urinary albumin excretion. Interestingly, imidapril improved
      asymptomatic dysphagia in patients with a history of stroke. In the same patients
      it increased serum substance P levels, while the angiotensin II receptor
      antagonist losartan was ineffective. These studies indicate that imidapril is a
      versatile ACE inhibitor. In addition to its effectiveness in the treatment of
      hypertension, CHF, and AMI, imidapril has beneficial effects in the treatment of
      diabetic nephropathy and asymptomatic dysphagia. Good tissue penetration and
      inhibition of tissue ACE by imidapril contributes to its effectiveness in
      preventing cardiovascular complications of hypertension. The major advantages of
      imidapril are its activity in the treatment of various cardiovascular diseases
      and lower incidence of cough compared with some of the older ACE inhibitors.

PMID- 12177689
TI  - The antiarrhythmic drug BRL-32872.
AB  - BRL-32872 is a new antiarrhythmic drug with balanced class-III and class-IV
      actions as categorized by the Vaughan-Williams classification. BRL-32872 blocks
      the rapid component of the cardiac delayed rectifier potassium channel IK(r)
      (IC(50) = 28 nM) and its molecular correlate HERG ("Human-ether-a-go-go related
      gene," IC(50) of 19.8 nM in cell lines) at low concentrations. It also inhibits
      the L-type calcium current (ICa) at higher concentrations (IC(50) = 2.8 microM).
      This dual concentration-dependent profile of action at higher concentrations may
      possibly prevent "torsades de pointes" ventricular arrhythmias, which is a
      dangerous side effect of many other class-III antiarrhythmic drugs. With BRL
      32872, an excessive prolongation of the action potential duration and consecutive
      QTc prolongation is prevented by a concentration-dependent increase of calcium
      channel block, resulting in the so-called "bell-shaped" profile of antiarrhythmic
      drug action. BRL-32872 is very effective in the treatment of ventricular
      arrhythmias in animal models of cardiac ischemia. In the ischemic hearts of
      animals the drug significantly reduced early afterdepolarization and ventricular
      tachycardia. The antiarrhythmic effect of BRL-32872 has not yet been demonstrated
      in humans.

PMID- 12177691
TI  - Nonpeptide factor Xa inhibitors: DPC423, a highly potent and orally bioavailable
      pyrazole antithrombotic agent.
AB  - DPC423, 1-[3-(aminomethyl)phenyl]-N-[3-fluoro-2'-(methylsulfonyl)[1,1'-biphenyl]
      4-yl]-3-(trifluoromethyl)-1H-pyrazole-5-carboxamide, is a synthetic, orally
      bioavailable, competitive, and selective inhibitor of human coagulation factor Xa
      (K(i) [nM]: factor Xa, 0.15; trypsin, 60; thrombin, 6000; plasma kallikrein, 61;
      activated protein C, 1800; factor IXa, 2200; factor VIIa, >15,000; chymotrypsin,
      >17,000; urokinase, >19,000; plasmin, >35,000; tissue plasminogen activator,
      >45,000; complement factor I, 44,000 [IC(50)]). In vitro, DPC423 produced
      anticoagulant effects in human plasma in which it doubled prothrombin time,
      activated partial thromboplastin time, and Heptest clotting time at 3.1 +/- 0.4,
      3.1 +/- 0.4, and 1.1 +/- 0.5 microM, respectively. In dogs, DPC423 had a good
      pharmacokinetic profile with an oral bioavailability of 57%, a plasma clearance
      of 0.24 L/kg/h, and a plasma half-life of 7.5 h. In rabbit and rat models of
      arteriovenous shunt thrombosis, DPC423 was an effective antithrombotic agent with
      an IC(50) of 150 and 470 nM, respectively. The antithrombotic effect of DPC423 is
      likely to be related to the inhibition of factor Xa but not to the inhibition of
      thrombin or due to direct inhibition of platelet aggregation. Therefore, based on
      potency, selectivity, efficacy, and oral bioavailability, DPC423 was selected for
      clinical development as an oral anticoagulant for the potential treatment of
      thrombotic disorders. Preliminary human data suggest that DPC423 is orally
      bioavailable in humans and has a long plasma half-life.

PMID- 12177690
TI  - Pharmacologic profile of the selective mitochondrial-K(ATP) opener BMS-191095 for
      treatment of acute myocardial ischemia.
AB  - ATP-sensitive potassium channel (K(ATP)) openers as a class protect ischemic
      myocardium. The protective effects are independent of vasodilator activity and
      effects on action potential shortening, actions typically associated with
      sarcolemmal K(ATP) activation. BMS-191095 is a novel mitochondrial K(ATP) opener
      which protects ischemic myocardium while having no electrophysiologic or
      vasodilator effects (determined in vitro and in vivo). The cardioprotective
      effects were determined in isolated rat hearts subjected to ischemia and
      reperfusion. Protective effects were deduced from increased time to contracture
      formation during ischemia, improved reperfusion recovery of contractile function,
      and reduced reperfusion LDH release. The cardioprotective effects of BMS-191095
      were observed at concentrations at which this compound selectively opened cardiac
      mitochondrial K(ATP) channels. This effect was consistent with the pharmacologic
      profile of this agent. The protective effects were abolished by mitochondrial
      K(ATP) inhibition. Unlike first-generation K(ATP) openers, BMS-191095 is expected
      to protect ischemic myocardium with little hemodynamic sequelae and without any
      proarrhythmic potential. BMS-191095 is potentially useful clinically as a
      cardioprotective agent. It is also a useful tool for basic research.

PMID- 12177704
TI  - [EARLY PREDICTOR OF SUSTAINED RESPONSE AT CHRONIC HEPATITIS C THERAPY: TOWARD A
      RATIONAL AND EFFECTIVE TREATMENT]

PMID- 12177705
TI  - [EARLY HEPATOCARCINOMA AT HOSPITAL CAYETANO HEREDIA(January 1969 - April 1997)
      CLINICAL AND LABORATORY FINDINGS]
AB  - In this work, 60 patients with an hepatocarcinoma diagnosis, corrobarated with
      hepatic biopsies at the Hospital Cayetano Heredia, between 1969 and 1997, are
      studied to determine clinical presentation and laboratory findings of this entity
      within us. The early hepatocarcinoma cases studied were 60. The age group that
      suffered mostly from this pathology was between 60 to 69 years (23.33%), followed
      by the age group of 20 to 29 years (20%). While the mean age was of 45 years.
      56.66% were male, and 43.33% were female. 56.66% of cases came from the Coast,
      30% from the Mountains, and 13.33% from the Jungle. Cronic and excessive alcohol
      ingestion appeared as background in 25% of cases. The average period of apparent
      disease was seven (7) weeks. The main symptoms at their admission were: abdominal
      mass sensation (81.66%), weight loss (81.66%) superior hemiabdominal pain (80%),
      and anorexia (60%). In 95% of cases the predominant sign was Hepatomegaly. The
      survival term of those patients whom we were able to follow-up was of less than
      six (6) months in 86.84 /x, less or equal to.

PMID- 12177706
TI  - [PROGNOSTIC SURVIVAL FACTORS IN GASTRIC CANCER WITH NEGATIVE REGIONAL NODES]
AB  - This discriptive and retrospective study evaluated 44 patients with histological
      proven node negative gastric cancer who underwent subtotal gastrectomy (n=42) or
      total gastrectomy (n=2) at Hospital Belen, Trujillo, Peru, between 1966 and 1996.
      The main objective was to determine the prognostic factors which influenced the
      five-year survival rate. There were 23 male, and 21 female (M:F = 1.1:1). Mean
      age was 60 10 years (which ranged from 26 to 81 years). Pathology mean time was
      of 16.3 13.6 month (which ranged from 1 to 84 months). The types of lymph node
      dissections were Do (n=2), D1 (n=29), and D2/D3 (n=3). The postoperative
      mortality rate was of 15.9%. In the total series, the 5-year survival rate was of
      38%; although, this rate increased to 56% in those patients who underwent D1D3
      lymphadenectomy. According to univariate analysis, using the log-rank test,
      prognosis was related with serum level of hemoglobin (p<0.05), clinical stage
      (p<0.01), curability (p<0.01), and type of lymphadenectomy (p<0.05). The clinical
      course was not related to age, gender, length of disease, palpable mass, gastric
      outlet obstructive syndrome, digestive hemorrhage, tumor size, location,
      macroscopic type, tumor depth, nor histologic type. We concluded that an early
      detection, the feasibility of a curative resection, and an extended
      lymphadenectomy were factors that affected survival in an individual patient with
      gastric cancer without lymph node involvement. These parameters must be
      considered to stratify patients for an adjuvant treatment.

PMID- 12177707
TI  - [STRONGYLOIDES STERCORALIS: CLINICAL SEVERE FORMS ASSOCIATED TO HTLV-1 INFECTION]
AB  - A study was conducted in Lima to determine the HTLV-1 infection rate among
      patients with different clinical patterns of Strongyloidiasis. This study
      included 21 patients with Strongyloides Stercoralis (St St) hyperinfection (Group
      1), and a group which consisted of sex and age matched asymptomatic healthy
      individuals whose stools were negative (Control Group Group 2). A third group
      included 33 patients with "probable hyperinfection", and another group of 63
      patients with intestinal Strongyloidiasis, without evidence of systemic disease,
      was included. Serum from each studied individual was analized to find HTLV-1/II
      and ELISA; positive cases were confirmed by Western Blot. The hyperinfection rate
      was significantly higher [85.7% (18/21)] compared to the control group [4.7%
      (1/21)] p<0.001. Likewise, the "probable hyperinfection" group was considerably
      higher [69.7% (23/33)] in comparison to the control group p<0.01. The group with
      intestinal Strongyloidiasis was [10% (6/62)] lower than patients with
      Strongyloides hyperinfection, but did not differ significantly (p>0.05) from the
      control group. In this last group 3/6 were HTLV-1 positive, and their follow-up
      showed they developed hyperinfection forms. We conclude that severe forms of St
      St are considerably associated to HTLV-1 infection in adults and children over 5
      years of age. No cases with HTLV-II were detected.

PMID- 12177708
TI  - [LIVER ORTHOTOPIC TRANSPLANTATION IN EXPERIMENTAL ANIMALS WITH VENO-VENOUS BYPASS
      PUMP HOSPITAL NACIONAL EDGARDO REBAGLIATI MARTINS-HNERM- 09/1996 TO 07/1998]
AB  - This study was carried at at the Hospital Nacional Edgardo Rebagliati Martins,
      from September 1996 to July 1998. 61 surgical procedures were performed in
      experimental animals, 39 in dogs and 22 in pigs. During the anhepatic phase, we
      used veno-venous bypass with centrifugal pumps and without systemic
      anticoagulation drugs in 6 animals, and passive venovenous bypass with systemic
      anticoagulation drugs in 8 animals. Experimental animals were sacrified two hours
      after the procedures were concluded in order to assess the status of vascular
      anastomosis and thrombus formation.

PMID- 12177709
TI  - [MINI-ENDOSCOPY OF THE BILIOPANCREATIC SYSTEM 1998]
AB  - Pancreaticoscopy is a method that is still in the midst of its development. The
      instruments available to date only allow inspection of proximally dilatated and
      extended ductal sections. Thanks to pancreaticoscopy, gastroenterological
      endoscopy has left the intestinal tract and achieved access to a glandular system
      with a unique histological wall structure. The extensive pathological anatomy of
      the pancreas makes intensive diagnostics desirable. Pancreaticoscopy should
      therefore be included in the diagnostic spectrum. However, this technique should
      always be performed with special circumspection, in particular with regard to the
      possible complications (acute pancreatitis) Ductal endoscopy of the bile duct and
      pancreatic duct are technically feasible and provide detailed evidence required
      for the diagnosis of diseases of the biliary and pancreatic system. The
      indications for cholangioscopy have, for the most part, been established,
      specifically therapeutic access to difficult gall stones. Pancreaticoscopy opens
      up new terrain in medical optics, although the relevance of this method, in
      conjunction with the outlay and technique required for its use, still have to
      find justification. The first prototypes for endoluminal sound have become
      available although this method is not expected to become a routine procedure in
      the near future.

PMID- 12177710
TI  - [GALLBLADDER PARAGONIMIASIS: REPORT OF ONE CASE]
AB  - We present an unusual case of Paragonimiasis in the gallbladder, with an
      unexpected finding in the anatomical examination. We comment this case and review
      its literature.

PMID- 12177711
TI  - [COMPLICATED PANCREATIC PSEUDOCYST: REPORT OF ONE CASE AND LITERATURE REVIEW]
AB  - We reported a complicated pancreatic pseudocyst (intracystic hemorrhage) seven
      months after an acute pancreatitis attack. A surgical drainage (internal
      cystogastrostomy) was carried out with excellent resolution. The clinical,
      radiological and therapeutic features of pancreatic pseudocysts are reviewed.

PMID- 12177713
TI  - [PREVENTION AND CONTROL OF INFECTIONS IN ENDOSCOPY]

PMID- 12177712
TI  - [THERAPEUTIC OPTIONS IN HEPATIC HYDATIDOSIS]

PMID- 12177714
TI  - [DUODENAL PEPTIC ULCER TREATMENT BY H. PYLORI ERADICATION: CONTROLED RANDOMIZED
      STUDY]
AB  - As Helicobacter pylori infection represents a very important causal factor in the
      development of duodenal peptic ulcer, several therapeutic trials have been
      developed in order to obtain an efficient eradication of the microorganism. The
      aim of our study has been to evaluate, in patients with duodenal peptic ulcer,
      the effect of double antibiotic short therapy associated to famotidine on the
      eradication of Helicobacter pylori, cicatrization of ulcerous lesion and the
      histological changes after the treatment. Forty patients with duodenal ulcer and
      Helicobacter pylori infection were distributed al random in two groups (I and
      II). Group I received tetracycline 2 gr per day plus furazolidone 400 mg per day
      for a week, and famotidine 40 mg per day for four weeks. Group II received just
      famotidine 40 mg per day for six weeks. Al the initial endoscopy, four biopsies
      were taken from the gastric antrurn for histological study and determination of
      Helicobacter pylori. The endoscopy was repeated between 6 and 8 weeks after the
      beginning of the antibiotic treatment, when four biopsies were taken again from
      the gastric antrum with the same purpose, and the results were compared. Twenty
      eight patients completed the study, 14 in group I and 14 in group II.
      Helicobacter pylori eradication was obtained in 85,7% of patients in group I and
      0% in group II (p=0.00002). Ulcer cicatrization was obtained in 100% of patients
      of group I compared to 85,7% of patients of group II (p=0.48). The histological
      degree of gastritis significantly diminished after the treatment in patients of
      Group I, in relation to the histological parameters of severity (p=0,002),
      activity (p=0,00002) and presence of lymphoid follicles (p=0.02). These changes
      were not significantly observed in group II. Two patients of group I had mild
      sideeffects (14,3%), and none of them was observed in group II (p=0.48). We
      concluded that the treatment used (tetracycline + furazolidone) was highly
      efficacious in the eradication of Helicobacter pylori, as well as in the
      cicatrization, reduction of antral gastric mucous inflammation, and a low rate of
      side-effects.

PMID- 12177715
TI  - [GASTROINTESTINAL SYMPTOMS IN ACQUIRED IMMUNODEFICIENCY SYNDROME (AIDS): A REVIEW
      OF ONE HUNDRED CASES AT "ARZOBISPO LOAYZA" HOSPITAL]
AB  - In 1996, one hundred health histories of HIV serum positive patients were
      reviewed using the Elisa and Western Blot techniques at the Arzobispo Loayza
      National Hospital. Such cases were defined according to Case Definition 1987
      CDC/WHO. 70% of HIV serum positive patients showed gastrointestinal symptoms
      according to the first medical examination. 57% of the patients were younger than
      30 years old, most of them were men (men/ women ratio: 2.7/1). 59% of the
      patients were heterosexual, 26% bisexual, and 15% homosexual. Chronic diarrhea
      was the main symptom, characterized by watering depositions over 10c/d. Giardia
      lamblia was isolated in 32% of the cases, while Isospora Belli in 16% and
      Criptosporidium in 12.5%. The laboratory findings of 7 patients (12.5%) were
      negative. Patients showed more than 10% weight loss. 10% of the patients had an
      anorectal disease while 7 of the patients (10%) had an hepatic-billiary disease.
      The odynophagia and dysphagia were explained by oropharyngeal candidiasis. 2.8%
      of the patients had acalculous cholecystitis; 2.8% suffered from acute pancreatic
      disease and 1.4% ascitis. The hepatic biochemistry was affected by the serum
      albumin reduction, the transaminases increase over 2-3 times compared to normal
      levels and the alkaline phosphatase, bilirrubina was about 5 mg. The high
      endoscopic diagnostic was in connection to the candida esophagitis and
      inflammatory pathology. In proctoscopy, condyloma acuminatum and perianal fistula
      were the most usual findings. The counting of CD4 leukocytes in 20 patients
      showed a great reduction of CD4 lymphocytes, in values lesser than 200 cel/mm3.
      The relation CD4/CD8 goes from 0.01 to 0.91 rates.

PMID- 12177716
TI  - [ENDOSCOPIC RETROGRADE CHOLANGIO PANCREATOGRAPHY(ERCP): EXPERIENCE IN 902
      PROCEDURES AT THE ENDOSCOPY DIGESTIVE CENTRE OF "ARZOBISPO LOAYZA" HOSPITAL]
AB  - On 1997, the Digestive Endoscopy Centre of "Arzobispo Loayza" Hospital was
      created with the cooperation of JICA (Japan International Cooperation Agency).
      902 ERCP were regularly performed from 1985 to August 1997. 902 tests were
      reviewed and 831 cases were left after excluding 16 ampulloma cases, 15
      cannulated or insufficient cases and 40 cases dealing only with pancreatic duct
      cannulation. The population is examined according to sex, age and diagnosis,
      establishing a relation among these three variables. Results showed that most of
      ERCP were made to women (3:1) with Choledocal Lithiasis (C.L.) and
      cholecistectomy antecedents, a greater frequency was observed in 56-65 year old
      women. In males, it was more frequent in people older than 65 years, they also
      had predominance of choledocal lithiasis, but malignant neoplasia of the biliary
      duct ranked in the third place. The highest incidence of C.L. with
      cholecistectomy antecedents suggests the performance of an appropriate evaluation
      of the biliary duct before surgery.

PMID- 12177717
TI  - [SURGICAL TREATMENT OF ESOPHAGEAL NEOPLASMS]
AB  - This report includes the experience of a surgical team from "Edgardo Rebagliati"
      Hospital, the Social Security Hospital in Lima, Peru. From 1987 to 1997 we carry
      out surgical management of epidermoid and glandular esophageal cancer having
      registered 74 cases. 52.7% of the cases had epidermoid cancer and 42.8% had
      adenocarcinoma. We had one case of primary melanoma and one case of primary
      lymphoma which were also subjected to esophagectomy. Almost all patients were in
      stages III and IV. Only one patient was considered to be in stage I, and one in
      stage II. These last ones have experienced more than 6 years of postoperatory
      survival. 67.4% of the patients showed tabaquism, alcoholism or both antecedents.
      In 50% of the cases the tumor was located in the lower third; in 45.9% it was
      located in the middle third, and in 4.05% in the upper third. 62.1 % of the
      patients were subjected to esophagectomy and gastrectomy of the upper third in
      block plus cervical esophagogastroplasty. 18.9% were subjected to total
      esophagogastrectomy and esophagocoloplasty, 14.8% were subjected to cervical
      esophagogastroplasty with gastric tube made with a major curvature and without
      esophagectomy. One patient was subjected to total pharyngothyroid esophagectomy
      with anastomosis at orofaringeal level due to pharyngoesophagic epidermoid
      cancer, including radical cervical dissection. The operative and perioperative
      mortality was of 4.05%, the morbidity was: 33.7% due to respiratory causes; 20.2%
      due to cervical fistula with spontaneous closure and 4.05% due to severe
      mediastinitis. Patients left the hospital at the 15th day average and began their
      oral feeding between the 10th and 14th day after the surgery. In all cases a
      progressive recovery of the nutritional level and the improve of life quality
      were achieved.

PMID- 12177718
TI  - [ACUTE CHOLECYSTITIS: COMPARATIVE STUDEY OF THREE MEDICAL-SURGICAL ALTERNATIVES]
AB  - Three alternatives of surgical treatment for acute cholescystitis were studied.
      The 40 patients integrating Group I were studied in a retrospective way and
      received conservative medical treatment and deferred conventional surgery. The 40
      patients integrating Group II were studied in a prospective way and they were
      operated according to conventional technique 72 hours before the beginning of the
      acute vesicular condition. The 40 patients integrating Group III were studied in
      a prospective way and they were operated using laparoscopic technique. The
      operation time, fall of temperature, the removal of the nasogastric tube, the
      postoperative pain, the oral tolerance and the postoperative hospitalization time
      were compared. We find out that there is a significant difference between all the
      aforementioned parameters and, particularly, between the conventional technique
      and the laparoscopic technique.

PMID- 12177719
TI  - [LAPAROSCOPIC APPENDECTOMY: EXPERIENCE IN THIRTY CASES]
AB  - Between September 1994 and February 1997, 30 patients with clinical diagnosis of
      acute appendicitis were subject of laparoscopic appendectomy (LA) at the "Stella
      Maris" Clinic in Lima - Peru. Only one conversion to an open procedure was
      practiced to a 69 years old woman with an appendiculate plastron. Out of the
      other 29 LA cases, 17 were women (58.6%) and 12 were men (41.4%) with an average
      age of 23 years, average surgery time of 94 minutes, average time of
      restablishment of food in-take 15 hr. and average post-operation time of
      hospitalization 27,1 hr. The anatomo-pathologic diagnosis revealed 11 cases of
      acute appendicitis, 1 case of suppurative acute appendicitis, 6 cases of acute
      appendicitis + peritonitis, 1 case of chronic periappendicitis, 6 cases of
      vascular congestion and/or follicular hyperplasia. There were also reported 3
      cases of vascular congestion and/or follicular hyperplasia associated to
      gynecological pathologies that were solved laparoscopycally. A minor wound
      infection was registered as a post-operative complication. Thus, it is concluded
      that the LA is a save method of low morbidity, applicable to children, very
      advantageous in women in fertile age, in obese or fat patients, in the cases of
      diagnostic doubt and in patients with complicated appendicitis.

PMID- 12177720
TI  - [DOUBLE EPIDERMOID CARCINOMA IN A DUPLICATE SMALL INTESTINE. REPORT OF A CASE AND
      LITERATURE REVISION]
AB  - It is postulated that duplications of the intestinal tract have malignant
      potential. A case of double epidermoid carcinoma derived from a tubular
      duplication of the terminal ileum is described. The neoplasias came from areas of
      squamous metaplasia located in the mucosal lining at both ends of the
      duplication, invading the wall of the duplicated intestine. No metastasizing to
      the regional lymph nodes appeared. The 32-years-old patient has no longer the
      disease eleven years after the surgical treatment. The purpose of this paper is
      to review the literature focusing on etiology, diagnosis and treatment.

PMID- 12177721
TI  - [MIXED INFECTION BY TRICHURIS TRICHIURA AND TRICHURIS VULPIS]
AB  - We present a case of mixed infection by Trichuris trichiura and Trichuris vulpis
      in a boy of 8 years old, coming from the state of Oaxaca in M xico. He presented
      abdominal pain, diarrhea with mucus and blood in addition to straining and
      tenesmus. We carried out differential identification between the two species of
      this gender, several treatments were administered and the symptoms disappear.
      But, the parasitic infection persisted until the last clinical control of the
      patient. We report the presence of important deformation of Trichuris eggs with
      the administration of mebendazole and albendazole being more effective the second
      product. We discuss about the importance of this clinical case and the
      epidemiological aspects in the transmission of man and dog nematodes.

PMID- 12177722
TI  - [HEMOBILIA: REPORT OF TWO CASES]
AB  - Hemobilia is defined as the hemorrhage within the biliary tree. Maybe, the
      abnormal communication between blood vessels and the billiary tree, is due to
      trauma, inflammatory disorders, infections, gallstones, tumors and coagulation
      disorders. Two cases, which diagnosis were made with retrograde endoscopic
      cholangio pancreatography, are reported here.

PMID- 12177723
TI  - Early relief of upper gastrointestinal dyspeptic symptoms: a survey of empirical
      therapy with pantoprazole in Canadian clinical practice.
AB  - BACKGROUND: Upper gastrointestinal symptoms attributable to gastroesophageal
      reflux disease or peptic ulcer are common, but the outcome of proton pump
      inhibitor therapy in clinical practice is not well documented. AIM: To assess the
      range of upper gastrointestinal acid-related symptoms in clinical practice and
      the rapidity of their response to pantoprazole (40 mg daily), after seven days of
      therapy. METHODS: A total of 726 Canadian physicians (65.3% family physicians)
      recorded a working diagnosis and alarm features in eligible patients, who then
      recorded the severity of eight upper gastrointestinal symptoms in a daily symptom
      diary during the first week of therapy. RESULTS: Complete data were obtained from
      2273 (37.3% male) of 3261 patients; physicians diagnosed reflux esophagitis alone
      (66.9%), peptic ulcer (9.7%), other upper gastrointestinal disorders (12.3%) and
      reflux esophagitis with another diagnosis (11.1%). Alarm features were common
      (29.6%), but a history of gastrointestinal blood loss was rare (less than 1%).
      Mean daytime heartburn scores decreased from 2.59 to 1.40, and epigastric pain
      scores decreased from 2.54 to 1.56 over the first week (P<0.00001); the
      proportions of patients who became symptom-free were 68.1% and 55.4%,
      respectively. Decreased mean symptom scores were also observed for acid
      regurgitation (2.21 to 1.35), bloating (2.47 to 1.57), nausea (2.03 to 1.36),
      slow digestion (2.51 to 1.56) and burping (2.56 to 1.69). The percentage of
      patients with severe or very severe symptoms decreased from 53.5% to 13.8% at day
      7. The physician's initial diagnosis was not predictive of outcome. CONCLUSIONS:
      In a predominantly primary care population with upper gastrointestinal acid
      related symptoms, proton pump inhibitor therapy produces prompt symptomatic
      relief in most patients. Potential alarm symptoms are common, and further
      research is required to determine the absolute risk of alarm symptoms and their
      implications for empirical therapy.

PMID- 12177724
TI  - The role of radiological imaging in the diagnosis of acute appendicitis.
AB  - Several strategies have been employed to improve the accuracy of the diagnosis of
      appendicitis and to reduce the associated perforation rate. Because clinical
      algorithms have been disappointing, many physicians resort to radiological
      modalities. Plain abdominal x-rays are nonspecific, barium enema examination has
      relatively low accuracy, scintigraphy scans require considerable time and are
      difficult to interpret, and magnetic resonance imaging is relatively unstudied.
      The most promising modalities are graded compression sonography and computed
      tomography. In expert hands, these techniques can achieve a high degree of
      accuracy. Nevertheless, most published studies have been marred by methodological
      difficulties. Moreover, ultrasound is more useful in detecting than in ruling out
      appendicitis. The radiological criteria for acute appendicitis, the accuracy of
      various imaging modalities and the limitations of the available research are
      described.

PMID- 12177725
TI  - Costing health care procedures: art or science?

PMID- 12177728
TI  - Pathophysiology of dyspnea.

PMID- 12177726
TI  - The cost of an upper gastroduodenal endoscopy: an activity-based approach.
AB  - The cost of medical procedures is often unknown, but is nevertheless crucial for
      setting reimbursement and health care policies. The cost of an upper
      gastroduodenal endoscopy was investigated in ambulatory adults in a large
      academic hospital in the province of Quebec, from the perspective of the
      hospital. An activity-based costing methodology was used to break down the
      procedure into a number of priory tasks, to which resources used at the
      department level (labour, equipment, materials) were allocated. The direct cost
      of performing an endoscopy ranged from $62 for an unsedated, unbiopsied patient
      to $89 for a sedated, biopsied patient. Not included in this amount were separate
      reimbursement fees of $15 for biopsy analysis and the $50 professional fee for
      the performing physician, which are charged directly to the Ministry of Health.
      Incorporating overall, general hospital fixed overhead costs raises the cost of
      the procedure substantially, by $41, as does the use of nonreusable biopsy
      forceps, which adds about $63 to the total cost of the procedure. Given the high
      proportion of overall, hospital-wide, overhead costs in the total cost of the
      procedure, allocation methods of these overhead costs in current hospital
      accounting systems should be improved to obtain a more precise estimate of the
      full cost of upper gastroduodenal endoscopy.

PMID- 12177729
TI  - The impact of body-weight components on forced spirometry in healthy italians.
AB  - Many studies have investigated lung function in relation to age and height among
      Caucasians, however, most of these studies did not consider the individual
      components of body weight. The objective of the present study was to study the
      effect of body weight components [bone-free lean body mass (BF-LBM), bone mineral
      content (BMC), and fat mass (FM)] measured by dual x-ray absorptiometry (DXA) on
      the lung-function variables (FVC, FEV1, and PEF) and to derive prediction
      equations for these variables in healthy adult Italians. Dynamic spirometric
      tests and body composition analysis by DXA were performed on 58 nonsmoking males,
      mean age ( +/-SE) 26.72 +/- 1.98 years and BMI 25.51 +/- 0.64 kg/m2, and 60
      nonsmoking females matched for age and BMI (29.61 +/- 1.65 years and 26.45 +/-
      1.05 kg/m2, respectively). Bivariate linear regression analysis showed the
      variables age, height, BF-LBM, BMC, and the interaction term BF-LBM*Height, but
      not weight and FM, to correlate significantly with lung-function variables for
      males and for females separately. Multiple linear regression analysis showed that
      sex, age, height, and BF-LBM*Height were significantly associated with FVC, FEV1,
      and PEF. The prediction equations developed for FVC, FEV1, and PEF on the basis
      of the independent variables i.e. sex, age (y), height (m), and BF-LBM*Height
      (kg. m) had a significantly higher cumulative correlation coefficient and a lower
      SEE compared with those based on age and height only. The present report suggests
      that the BF-LBM, expressed independently from height, can be considered for
      predicting lung-function variables.

PMID- 12177730
TI  - Effects of an eosinophil chemotaxis inhibitor, TAK-661, on antigen-induced
      asthmatic responses in allergic sheep.
AB  - Eosinophils have been shown to play a role in allergen-induced airway responses.
      The aim in this study was to examine the effects of TAK-661, a newly developed
      product as a specific inhibitory agent of eosinophil chemotaxis, on antigen
      induced asthmatic responses in allergic sheep model. Seven Ascaris-sensitive,
      "dual-respondent" allergic sheep were provocated by an Ascaris suum antigen or
      phosphate-buffered saline 2 hrs after intra-stomach administration of TAK-661 or
      a placebo. Pulmonary resistances were measured throughout the experiment, and
      airway responsiveness to methacholine, bronchoalveolar lavage (BAL), and
      histological examination were performed 8 hrs after the antigen challenge.
      Antigen provocation induced dual-phase bronchoconstriction, eosinophilia in BAL
      and eosinophil infiltration into the airway wall, and an increase in airway
      responsiveness in placebo-treated sheep. The administration of TAK-661
      significantly reduced the bronchoconstriction during the late phase, along with
      the inhibition of eosinophilia in BAL and the eosinophil infiltration into the
      airway wall. TAK-661 had a tendency to reduce early-phase bronchoconstriction and
      airway hyperresponsiveness, but there were no significant differences. These
      findings suggest that the eosinophil accumulation into the airway induced by
      antigen provocation may contribute to the development of late-phase
      bronchoconstriction, however, the development of airway hyperresponsiveness
      during late asthmatic response may not always be due to only eosinophilic
      inflammation in the airway.

PMID- 12177731
TI  - Relationship between chemotherapy response of small cell lung cancer and P
      glycoprotein or multidrug resistance-related protein expression.
AB  - The resistance of small cell lung cancer (SCLC) to anticancer drugs is a serious
      clinical problem often encountered during chemotherapy. Therefore, how to prevent
      this drug resistance need to be investigated. Multidrug resistance 1 (MDR1) gene
      and multidrug resistance-related protein (MRP) gene, two genes known to be
      associated with the development of drug resistance, are very common in SCLC. The
      purpose of this study was to evaluate retrospectively the relationship between
      chemotherapy responses to MDR1 gene encodes 170 kDa P-glycoprotein (Pgp)
      expression or MRP gene encodes 190 kDa MRP expression in SCLC. Before
      chemotherapy, multiple nonconsecutive sections of the bronchoscopy biopsy
      specimens of SCLC from 50 patients were analyzed immunohistochemically to detect
      Pgp and MRP expressions. Chemotherapy responses of the 50 patients were evaluated
      in the third month after completion of treatment by clinical and radiological
      methods. Of the 23 SCLC patients with poor response to chemotherapy, 11 had
      positive Pgp and MRP expressions, 2 had positive Pgp but negative MRP
      expressions, 6 had positive MRP but negative Pgp expressions, and 4 patients had
      negative Pgp and MRP expressions. All 27 SCLC patients with good response had
      negative Pgp and MRP expression. Immunohistochemical analyses of Pgp or MRP
      expression are potential tools for predicting patients' chemotherapy response in
      SCLC.

PMID- 12177732
TI  - Objective evidence of impairment of alveolar integrity in patients with non
      insulin-dependent diabetes mellitus using radionuclide inhalation lung scan.
AB  - The alveolar integrity (AI) in 60 patients of noninsulin-dependent diabetes
      mellitus (NIDDM) who had normal chest X-ray findings and pulmonary function test
      was measured by technetium-99m (Tc-99m) diethyltriamine pentaacetic acid (DTPA)
      and Tc-99m hexamethylpropylen amine (HMPAO) radioaerosol inhalation lung scan
      (lung scan). The degree of AI damage in NIDDM was presented as the clearance rate
      (%/min) of hydrophilic Tc-99m DTPA and lipophilic Tc-99m HMPAO radioaerosols from
      the lungs. The AI of NIDDM patients was compared with the AI of 40 normal
      controls. The results show that (1) the clearance rate of Tc-99m DTPA
      radioaerosols was faster than those of Tc-99m HMPAO radioareosols in either NIDDM
      patients or normal controls over any portion of the lungs, (2) the clearance
      rates of both Tc-99m DTPA and Tc-99m HMPAO radioaerosols were faster in NIDDM
      patients than those in normal controls over any portion of the lungs. Our
      findings concluded that (1) at least two different clearance mechanisms of
      radioaerosols in the lungs are working; and (2) the AI damage in NIDDM patients
      happened in both hydrophilic and lipophilic parts of the alveoli. In addition,
      the AI damage found by faster clearance rates of both Tc-99m DTPA and HMPAO
      radioaerosols may provide the other objective evidence of lung complications in
      NIDDM patients, which are different from the traditional studies such as chest X
      ray or pulmonary function test.

PMID- 12177734
TI  - The ketolide antibiotic ABT-773 is a specific inhibitor of translation and 50S
      ribosomal subunit formation in Streptococcus pneumoniae cells.
AB  - ABT-773 is a new 3-keto macrolide antibiotic that has been shown to be very
      effective against infections by Gram-positive microorganisms. This work examines
      its inhibitory effects in cells of Streptococcus pneumoniae. ABT-773 caused a
      proportional decline in cell growth rates and viability with an IC(50) of 5
      ng/ml. Protein synthesis in these cells was reduced by 50% at an antibiotic
      concentration of 2.5 ng/ml. This compound was also found to be a very effective
      inhibitor of the formation of the 50S ribosomal subunit in growing cells. Pulse
      and chase labeling assays revealed a reduced rate of 50S synthesis in antibiotic
      treated cells. At 2 ng/ml, the rate was reduced to 33% of the control synthesis
      rate. An IC(50) of 5 ng/ml was found for the effect on this process, indicating
      an equal effect of the drug on translation and assembly. Synthesis of the 30S
      ribosomal subunit was unaffected by this antibiotic. The effects of ABT-773 in S.
      pneumoniae are compared with those of the related ketolide antibiotic
      telithromycin in S. pneumoniae and in Staphylococcus aureus.

PMID- 12177735
TI  - Molecular differentiation of the heterocystous cyanobacteria, Nostoc and
      Anabaena, based on complete NifD sequences.
AB  - The segregation of Nostoc and Anabaena into separate genera has been debated for
      some time. The nitrogen fixation gene nifD was completely sequenced from
      representatives of these genera and analyzed phylogenetically, by using the
      representatives of other genera of the heterocystous cyanobacteria as outgroups.
      We were clearly able to differentiate between Nostoc and Anabaena in all analyses
      used. Our data suggest that Nostoc and Anabaena should remain as separate genera.

PMID- 12177736
TI  - Characterization of salinity-tolerant mutant of Anabaena doliolum exhibiting
      multiple stress tolerance.
AB  - Results show that an isolated mutant of the cyanobacterium Anabaena doliolum is a
      fast-growing strain. It exhibits approximately twofold higher NaCl tolerance than
      the wild type. It also reveals cross-resistance against the herbicide 3-(3,4
      dichlorophenyl)-1,1-dimethylurea (DCMU), drug bacitracin, and LiCl. Further, an
      improved LiCl tolerance property of both the mutant and wild-type strains at high
      concentration of NaCl (40 m M) may be interpreted in terms of competitive
      inhibition of the Li(+) uptake by Na(+) ions, whereas bacitracin resistance in
      these organisms is described to be the result of an alteration in the drug
      transporting channels of membrane. The multiple stress tolerance property of the
      A. doliolum may be attributed to altered membrane characteristics in the mutant
      strain, leading to reduced intake of such toxicants.

PMID- 12177737
TI  - Interaction of bacterial toxin with leukocytes measured by flow cytometry.
AB  - Enterobacter cloacae toxin was purified in the form of monomer and polymer. Both
      forms stimulated the generation of reactive oxygen species (ROS) at sublytic
      concentration; the oxidative stress produced was studied by using
      chemiluminescence (CL). The alteration generated caused death of leukocytes,
      especially at high toxin concentration. Polymeric toxin produced more oxidative
      stress than the monomeric one. Cytometry allowed the detection of more toxin
      binding to neutrophils rather than to monocytes or lymphocytes. There was binding
      at 4 degrees C, and the amount of toxin in the cells increased at 37 degrees C.
      The interaction of toxin with leukocytes was evident even after 100 degrees C
      treatment of toxin during 5 min. The incubation with 2-mercaptoethanol was not
      necessary for toxin binding.

PMID- 12177739
TI  - Resistance to cadmium and zinc in Acidiphilium symbioticum KM2 is plasmid
      mediated.
AB  - The acidophilic heterotroph, Acidiphilium symbioticum KM2, is highly resistant to
      several metals and harbors three plasmids of 3.8, 7.1, and 56 kb in size. The
      bacterium becomes extremely sensitive to metals when it is cured of its plasmids.
      A mini-plasmid library was constructed by ligating the plasmid DNA fragments
      generated by MboI partial digestion into the BamHI site of pBluescriptII KS+. The
      Lac(-)Amp(r) transformants of Escherichia coli DH5alpha, isolated after
      transformation with the library, were counter-selected on Cu(2+), Cd(2+), Ni(2+),
      and Zn(2+)-containing plates. Only Cd(2+)- and Zn(2+)-resistant colonies were
      developed, and, after screening, four types of recombinant plasmids designated as
      pNM201 (7.2 kb), pNM206 (3.4 kb), pNM208 (4.5 kb), and pNM215 (4.9 kb) were
      obtained. The DNA insert in pNM206 hybridized strongly with the 3.8-kb plasmid
      and weakly with the 7.1-kb plasmid of Acidiphilium symbioticum KM2. The DNA
      insert in pNM215 hybridized only with the 7.1-kb plasmid. These results strongly
      suggested that resistance to cadmium and zinc in A. symbioticum KM2 is mediated
      by these plasmids. The smallest insert of 422 bp in pNM206 conferring metal
      resistance in E. coli has no sequence similarity with the reported metal
      resistant genes. All the putative ORFs are significantly rich (up to 37%) in
      basic amino acids, mainly arginine.

PMID- 12177738
TI  - Cloning and function of sanQ: a gene involved in nikkomycin biosynthesis of
      Streptomyces ansochromogenes.
AB  - A 2.8-kb BamHI fragment was cloned from the cosmid library of Streptomyces
      ansochromogenes by using the 1.35-kb BamHI- ApaI fragment of sanO involved in
      nikkomycin biosynthesis as a probe. Sequence analysis showed that the BamHI
      fragment contains an open reading frame with 1191 bp, which was designated sanQ.
      In search of databases, the deduced product of sanQ gene has 56% similarity to
      the cytochrome P450. sanQ gene was inactivated by insertion of a kanamycin
      resistance gene. The resulting disruptants failed to produce nikkomycin X, but
      nikkomycin Z was at the same level as the wild type, indicating that sanQ is
      essential for the biosynthesis of nikkomycin X.

PMID- 12177740
TI  - Expression of Bacillus stearothermophilus LV cadmium resistance genes in
      Escherichia coli causes hypersensitivity to cadmium chloride.
AB  - Determination of the nucleotide sequence of a 4.5-kb chromosomal DNA fragment of
      Bacillus stearothermophilus LV revealed two open reading frames (ORFs) of 121 and
      727 amino acids (aa) that exhibit a high degree of similarity with the cadC and
      cadA cadmium resistance genes of a number of microorganisms. Transfer and
      expression of the B. stearothermophilus LV cadA or cadC/ cadA genes in E. coli
      caused increased cadmium chloride susceptibility in the bacterial host. Transfer
      of cadC alone did not result in any detectable phenotypic change in E. coli.

PMID- 12177741
TI  - Structural features of the lac promoter affecting gusA expression in
      Lactobacillus casei.
AB  - With the aim of designing efficient expression systems for Lactobacillus casei,
      different factors affecting gene expression from the strong and highly modulated
      lac promoter have been systematically analyzed, by using the Escherichia coli
      beta-glucuronidase gene (gusA) as reporter. The activity of this enzyme (GUS) was
      quantified when plac:: gusA fusions were cloned in plasmids with different copy
      number or when gusA was inserted in the chromosomal lactose operon (single copy).
      Results showed a clear gene dosage effect and a positive influence of the native
      lac operon transcription and translation signals on GUS expression.

PMID- 12177742
TI  - Molecular and physiological differentiation between pathogenic and nonpathogenic
      Acanthamoeba.
AB  - In this study, 14 isolates of Acanthamoeba from both clinical and environmental
      sources belonging to seven different species were assayed for tolerance of high
      osmotic pressure, temperature tolerance, extracellular proteases, and cytopathic
      effects (CPE) on immortalized rabbit corneal epithelial cells. On the basis of
      the results, amoeba isolates were divided into pathogenic and nonpathogenic
      groups. Ribosomal DNA sequencing was performed on these isolates. Phylogenetic
      relationships revealed that all the pathogenic strains tested clustered together
      as one group, while nonpathogenic strains clustered into other groups. Sequence
      comparisons with previously published sequences determined that among the six new
      pathogenic isolates used in this study, five belong to T4 genotype and one to
      T11. This is the first report of a T11 genotype being found in Acanthamoeba
      keratitis.

PMID- 12177743
TI  - Statistical media optimization and production of ITS alpha-amylase from
      Aspergillus oryzae in a bioreactor.
AB  - The production of an intermediate temperature-stable (ITS) alpha-amylase from
      Aspergillus oryzae was studied by using a central composite design with three
      independent variables, viz., starch, yeast extract, and K(2)HPO(4). The model
      equation provided a suitable model for the response surface for alpha-amylase
      production, and, from the optimal concentrations of the medium components, a
      model was predicted, which was then used for enzyme production in a 150-L
      bioreactor. In the bioreactor studies, the enzyme yields (161 U/ml) were similar
      to that of the shake flask (133 U/ml); however, the time required for maximum
      alpha-amylase production in the bioreactor was reduced to 48 h compared with 120
      h in shake flask cultures. An increased level of phosphate in the medium and low
      inoculum size were necessary to control the excessive foaming in the bioreactor;
      however, control of the pO(2) level and agitation was not mandatory for enzyme
      production. The peak enzyme production coincided with the increase in pH of the
      fermentation broth and was maximal when the pH of the system was above 7.5. Thus,
      in the present study, pH acted as an indicator of the initiation or end of the
      enzyme synthesis or of the fermentation cycle.

PMID- 12177744
TI  - Effect of light and oxygen and adaptation to changing light conditions in a
      photosynthetic mutant in which the LHII complex of Rhv. sulfidophilum was
      heterologously expressed in a strain of Rb. capsulatus whose puc operon was
      deleted.
AB  - In this paper we show the effect of oxygen and light on the expression of the
      photosynthetic apparatus of a mutant heterologously expressing the puc operon.
      This mutant was obtained by introducing in trans an expression plasmid, bearing
      the puc A, B, and C genes of Rhv. sulfidophilum, as well as its own promoter, in
      an LHII(-) mutant of Rb. capsulatus. The results showed that oxygen and light
      repressed LHII expression. Even low-light intensities lowered the LHII content to
      undetectable levels by spectrophotometry or by SDS-PAGE. In high-light grown
      cells, where the relative ratios of LHI and LHII complexes were significantly
      diminished, we were able to detect LHII complexes. Under the latter condition,
      the absorption spectrum showed that some pigment accumulated in the membrane even
      in the absence of cell division. These pigments were used in a later step to
      assemble LHII complexes, when the high-light grown cells were transferred to
      semiaerobiosis in the dark. Transition of high-light grown cells to low-light
      conditions allowed us to study the adaptability of these heterologous mutant
      cells. We observed that adaptation never occurred, in part probably owing to
      energy limitation.

PMID- 12177745
TI  - Protection from UV-B damage of mosquito larvicidal toxins from Bacillus
      thuringiensis subsp. israelensis expressed in Anabaena PCC 7120.
AB  - A transgenic strain of the nitrogen-fixing filamentous cyanobacterium Anabaena
      PCC 7120 protected expressed delta-endotoxin proteins of Bacillus thuringiensis
      subsp. israelensis from damage inflicted by UV-B, a sunlight component that
      penetrates Earth's ozone layer. This organism, which serves as a food source to
      mosquito larvae and could multiply in their breeding sites, may solve the
      environment-imposed limitations of B. thuringiensis subsp. israelensis as a
      mosquito biological control agent.

PMID- 12177746
TI  - Detection of enterotoxin genes in mosquito-larvicidal Bacillus species.
AB  - The presence of the B component of hemolysin BL (hblA), enterotoxin BceT (bceT),
      and enterotoxin S (entS) genes in mosquito-larvicidal Bacillus sp., including 25
      B. sphaericus and 4 B. thuringiensis subsp. israelensis strains, has been
      analyzed by multiplex PCR in this study. The results showed that all four B.
      thuringiensis strains contain the hblA gene and the sequences of bceT and entS
      genes. However, none of the enterotoxin gene sequences were detected in the B.
      sphaericus strains. The enterotoxin production in all strains has also been
      analyzed by using two commercial immunoassay kits (TECRA and RPLA), and it has
      been proved that all the B. thuringiensis strains and one B. cereus strain can
      produce enterotoxins during growth. No enterotoxin activity could be detected in
      B. sphaericus strains.

PMID- 12177747
TI  - In vitro inhibition of Salmonella enterica serovars choleraesuis and typhimurium,
      Escherichia coli F-18, and Escherichia coli O157:H7 by a porcine continuous-flow
      competitive exclusion culture.
AB  - A competitive exclusion (CE) culture of porcine cecal bacteria was developed as a
      continuous-flow culture in chemostats, was designated RPCF, and was used as a
      model to determine its usefulness against in vitro colonization by Salmonella
      enterica serovars Typhimurium and Choleraesuis, Escherichia coli strain F-18, and
      E. coli serotype O157:H7 (933). Chemostats with or without RPCF were inoculated
      with 10(6) colony-forming units (CFU)/ml of Typhimurium, Choleraesuis, F-18, or
      O157:H7. Chemostats were sampled for salmonellae and E. coli at 15 min, 7 h, and
      every 24 h thereafter. In control chemostats without RPCF, Typhimurium,
      Choleraesuis, F-18, and O157:H7 rapidly established colonization and had
      concentrations of 10(6) CFU/ml for 96-120 h post-inoculation. In the chemostats
      that contained RPCF, reductions (P < 0.05) of Choleraesuis, F-18, and O157:H7
      were observed at 24 h post-inoculation. Typhimurium was decreased (P < 0.05) at
      48 h post-inoculation, and by 120 h post-inoculation, all chemostats were
      negative for the four challenge microorganisms. These results demonstrate that
      RPCF cultures were able to inhibit the growth of Typhimurium, Choleraesuis, and
      E. coli strains F-18 and O157:H7 in vitro and suggest the potential for the use
      of CE in swine to prevent disease induced by these microorganisms.

PMID- 12177748
TI  - Liver lead concentrations of several bird species from the western James bay
      region of northern Ontario, Canada: do the data support the Canadian nontoxic
      legislation?

PMID- 12177750
TI  - Seasonal variations in cadmium concentrations of plant leaves.

PMID- 12177749
TI  - Exposure to mercury in the urban population of Rio Branco City, state of Acre,
      Brazil.

PMID- 12177751
TI  - Metal concentrations in rice and pulses of Samta village, Bangladesh.

PMID- 12177752
TI  - Variation of copper, iron, and zinc levels in Pekmez products.

PMID- 12177753
TI  - Cadmium-induced apoptosis in h9c2, a7r5, and c6-glial cell.

PMID- 12177754
TI  - Potential exposure to pesticides in Nordic greenhouses.

PMID- 12177755
TI  - Cytotoxicity of dental impression materials.

PMID- 12177756
TI  - Inhibition of plasma cholinesterase and acute toxicity of monocrotophos in a
      neotropical fish Prochilodus lineatus (pisces, curimatidae).

PMID- 12177757
TI  - Toxic effects of cypermethrin on certain hematological aspects of fresh water
      fish Channa punctatus.

PMID- 12177758
TI  - High tolerance of alderfly larvae (Sialis spp: Megaloptera) to metals is not
      affected by water pH.

PMID- 12177759
TI  - Lethality of copper sulfate and copper-treated nets to juvenile haddock,
      Melanogrammus aeglefinus L.

PMID- 12177760
TI  - Characterization of sodium, potassium, ATPase activity in the gills of Pimephales
      promelas (fathead minnow): influence of in vitro exposure to lead.

PMID- 12177761
TI  - Copper acute toxicity tests with the sand crab Emerita analoga (Decapoda:
      Hippidae): a biomonitor of heavy metal pollution in Chilean coastal seawater?

PMID- 12177762
TI  - Perturbations of population growth in a microcosm by industrial metal plating and
      ice cream mills wastewater and landfill leachate.

PMID- 12177763
TI  - Distribution of cadmium, copper, iron, manganese, lead, and zinc in spinner
      dolphins Stenella longirostris stranded in La Paz lagoon, southwest gulf of
      California.

PMID- 12177764
TI  - Acute toxicity of the fungicide copper oxychloride to tadpoles of the bullfrog
      Rana catesbeiana.

PMID- 12177765
TI  - Acute and chronic toxicity of arsenic to some aquatic organisms.

PMID- 12177766
TI  - Treatment of H-acid wastewater by photo-Fenton reagent combined with a
      biotreatment process: a study on optimum conditions of pretreatment by a photo
      Fenton process.

PMID- 12177767
TI  - Influence of moisture on chemical transferability from a nylon carpet.

PMID- 12177768
TI  - Movement and persistence of methamidophos in vegetable agroecosystem.

PMID- 12177769
TI  - Persistent organochlorine pesticide contamination of birds collected in
      Connecticut during the year 2000.

PMID- 12177770
TI  - Reduction of polychlorinated dibenzo- p-dioxins and dibenzofurans levels in
      chloranil from China.

PMID- 12177771
TI  - Fluctuations in prevalence of cervical human papillomavirus in women frequently
      sampled during a single menstrual cycle.
AB  - In the last few years much attention has been focused on the implementation of
      human papillomavirus detection in population based screening programmes to
      identify women at risk for cervical cancer. Short-term fluctuations in prevalence
      of human papillomavirus were investigated within a single menstrual cycle. The
      highest prevalence was found at the follicular phase (55%), whereas the
      cumulative prevalence was 75%.

PMID- 12177772
TI  - Lymphadenectomy and adjuvant therapy in endometrial carcinoma: role of adjuvant
      chemotherapy.
AB  - To evaluate the therapeutic benefit of lymphadenectomy and adjuvant therapy, in
      particular chemotherapy, we retrospectively analysed survival rates and patterns
      of recurrence of endometrioid adenocarcinoma in 106 patients who underwent
      surgery including retroperitoneal lymphadenectomy. Adjuvant chemotherapy was
      administered to 46 patients (42 received a platinum-based regimen) and pelvic
      irradiation to 12. The 5-year survival rate of 23 patients with lymph node
      metastasis was worse than that of patients without lymph node metastasis (60% vs
      96%, P<0.0001). Recurrence was observed in 14 patients (10 patients with
      chemotherapy, two with irradiation, and two without adjuvant therapy); the first
      site of recurrence was in distant sites in 12 patients; recurrence in the pelvic
      sidewall or exclusively in lymph nodes was not observed. The 5-year survival rate
      of 18 patients with lymph node metastasis treated with chemotherapy, was 61%
      including all 14 with macroscopically positive nodes and all nine with paraaortic
      metastasis. Of seven patients with bulky positives nodes, three patients with
      bulky paraaortic nodes died of the disease, three of the four patients with bulky
      pelvic but without bulky paraaortic nodes had no recurrence. In summary,
      lymphadenectomy may afford a survival benefit via the debulking of
      macroscopically positive nodes, and the predominance of distant recurrences
      suggests that chemotherapy is a suitable choice as an adjuvant therapy in
      endometrial carcinoma after lymphadenectomy.

PMID- 12177773
TI  - Semen cryopreservation, utilisation and reproductive outcome in men treated for
      Hodgkin's disease.
AB  - Between 1978 and 1990, 122 men underwent semen analysis before starting
      sterilising chemotherapy for Hodgkin's disease. Eighty-one (66%) had semen
      quality within the normal range, 25 were oligospermic (<20 x 10(6) sperm per ml)
      and five were azoospermic (no sperm in the ejaculate). Semen from 115 men was
      cryopreserved and after a median follow-up time of 10.1 years, 33 men have
      utilised stored semen (actuarial rate 27%) and nine partners have become pregnant
      resulting in 11 live births and one termination for foetal malformation.
      Actuarial 10 year rates of destruction of semen before death or utilisation and
      death before utilisation are 19% and 13% respectively. This retrospective cohort
      study demonstrates that approximately one-quarter of men utilising cryopreserved
      semen after treatment for Hodgkin's disease obtain a live birth. The high non
      utilisation rate is intriguing and warrants further investigation.

PMID- 12177774
TI  - Concurrent administration of Docetaxel and Stealth liposomal doxorubicin with
      radiotherapy in non-small cell lung cancer : excellent tolerance using
      subcutaneous amifostine for cytoprotection.
AB  - The substantial augmentation of the radiation sequelae during chemo-radiotherapy
      with novel drugs masks the real potential of such regimens. In this study we
      examined whether subcutaneous administration of amifostine can reduce the
      toxicity of a highly aggressive chemo-radiotherapy scheme with Stealth liposomal
      doxorubicin (Caelyx and Docetaxel (Taxotere in non-small cell lung cancer. Twenty
      five patients with stage IIIb non-small cell lung cancer were recruited in a
      phase I/II dose escalation trial. The starting dose of Taxotere was 20 mg m(-2)
      week and of Caelyx was 15 mg m(-2) every two weeks, during conventionally
      fractionated radiotherapy (total dose of 64 Gy). The dose of Taxotere/Caelyx was,
      thereafter, increased to 20/25 (five patients) and 30/25 mg m(-2) (15 patients).
      Amifostine 500 mg was given subcutaneously before each radiotherapy fraction,
      while an i.v. amifostine dose of 1000 mg preceded the infusion of docetaxel. The
      'in-field' radiation toxicity was low. Grade 3 esophagitis occurred in 9 out of
      25 (36%) patients. Apart from a marked reduction of the lymphocyte counts, the
      regimen was deprived from any haematological toxicity higher than grade 1. No
      other systemic toxicity was noted. The CR and CR/PR rates in 15 patients treated
      at the highest dose level was 40% (6 out of 15) and 87% (13 out of 15)
      respectively. It is concluded that the subcutaneous administration of amifostine
      during high dose Taxotere/Caelyx chemo-radiotherapy is a simple and effective way
      to render this aggressive regimen perfectly well tolerated, by reducing the
      systemic and the 'in-field' toxicity to the levels expected from simple
      conventional radiotherapy. The impressive tolerance and the high CR rate obtained
      encourages the conduct of a relevant randomized trial to assess an eventual
      survival benefit in patients with non-small cell lung cancer.

PMID- 12177775
TI  - A 'modified de Gramont' regimen of fluorouracil, alone and with oxaliplatin, for
      advanced colorectal cancer.
AB  - The standard de Gramont (dG) regimen of fortnightly leucovorin, bolus
      fluorouracil and 22-h infusion of fluorouracil, d1+2, and the same regimen plus
      oxaliplatin, are effective but also cumbersome. We therefore present simplified
      'Modified de Gramont' (MdG) regimens. Forty-six advanced gastrointestinal cancer
      patients entered a dose-exploring study of MdG, including an expanded cohort of
      colorectal cancer patients at optimum dose. Treatment (fortnightly) comprised: 2
      h i.v.i. leucovorin (350 mg d,l-LV or 175 mg l-LV, not adjusted for patient
      surface area); bolus fluorouracil (400 mg m(-2)), then ambulatory 46-h
      fluorouracil infusion (2000-3600 mg m(-2), cohort escalation). Subsequently, 62
      colorectal patients (25 unpretreated; 37 fluorouracil-resistant) received MdG
      plus oxaliplatin (OxMdG) 85 mg m(-2). Fluorouracil pharmacokinetics during MdG
      were compared with dG. The optimum fluorouracil doses for MdG alone were
      determined as 400 mg m(-2) bolus + 2800 mg m(-2) 46-h infusion. A lower dose of
      400 mg m(-2) bolus + 2400 mg m(-2) infusion which, like dG produces minimal
      toxicity, was chosen for the OxMdG combination. Fluorouracil exposure (AUC(0-48
      h)) at this lower dose is equivalent to dG. With OxMdG, grade 3-4 toxicity was
      rare (neutropenia 2.8% cycles; vomiting or diarrhoea <1% cycles), but despite
      this there were two infection-associated deaths. Oxaliplatin was omitted for
      cumulative neurotoxicity in 17 out of 62 patients. Objective responses in
      colorectal cancer patients were: 1st-line MdG (22 assessable): PR=36%, NC=32%,
      PD=32%. 1st-line OxMdG (24 assessable): CR/PR=72%; NC=20%; PD=8%; 2nd line OxMdG
      (34 assessable): PR=12%; NC=38%; PD=50%. MdG and OxMdG are convenient and well
      tolerated. OxMdG was particularly active as 1st-line treatment of advanced
      colorectal cancer. Both regimens are being further evaluated in the current UK
      MRC phase III trial.

PMID- 12177776
TI  - Microsatellite instability and intratumoural heterogeneity in 100 right-sided
      sporadic colon carcinomas.
AB  - Microsatellite instability has been proposed as an alternative pathway of
      colorectal carcinogenesis. The aim of this study was to evaluate the interest of
      immunohistochemistry as a new tool for highlighting mismatch repair deficiency
      and to compare the results with a PCR-based microsatellite assay. A total of 100
      sporadic proximal colon adenocarcinomas were analysed. The expression of hMLH1,
      hMSH2 and hMSH6 proteins evaluated by immunohistochemistry was altered in 39% of
      the cancers, whereas microsatellite instability assessed by PCR was detected in
      43%. There was discordance between the two methods in eight cases. After further
      analyses performed on other tumoural areas for these eight cases, total
      concordance between the two techniques was observed (Kappa=100%). Our results
      demonstrate that immunohistochemistry may be as efficient as microsatellite
      amplification in the detection of unstable phenotype provided that at least two
      samples of each carcinoma are screened, because of intratumoural heterogeneity.

PMID- 12177777
TI  - Production and characterisation of a recombinant scFv reactive with human
      gastrointestinal carcinomas.
AB  - SC142-reactive antigen are highly glycosylated glycoproteins expressed on tissues
      of gastric and colon cancers but not on normal tissues. Murine SC142 antibody
      specific for the SC142-reactive antigen has been produced by immunisation with
      SNU16 stomach cancer cells. However, SC142 antibody has several potential
      problems such as high immunogenicity and poor tumour penetration owing to their
      large size. To improve tumour penetration potential in vivo, recombinant single
      chain fragments have been produced using the original hybridoma cells as a source
      of variable heavy- and variable light-chain-encoding antibody genes. The use of
      the polymerase chain reaction, expression cloning technology and gene expression
      systems in E. coli has led to the production of SC142 single-chain fragments,
      which was similar in activity to the SC142 parent antibody confirmed by
      immunohistochemistry. Analysis by DNA sequencing, SDS-PAGE and Western blotting
      has demonstrated the integrity of the single-chain fragments. Competitive ELISA
      showed that SC142 single-chain fragments originated from parent SC142 antibody.
      BIAcore biosensor binding experiments showed that the SC142 single-chain
      fragments had an ideal dissociation rate constant as a tumour imaging reagent.
      These results illustrate the potential application of these novel products as an
      immunodiagnostic and further immunotherapeutic reagent.

PMID- 12177779
TI  - Identification of mRNAs differentially-expressed between benign and malignant
      breast tumour cells.
AB  - Two suppression subtracted cDNA libraries have been constructed, one containing
      cDNAs to mRNAs present at a higher level in a benign human breast tumour-derived
      cell line relative to the malignant mammary cell line, MCF-7, and the other
      containing cDNAs present at a higher level in the MCF-7 cells relative to the
      benign cells. Randomly-picked cloned DNAs have been sequenced yielding 29 and 128
      different cDNAs from the benign and malignant libraries, respectively. Using
      reverse Northern hybridisation, 76% and 83% of the cDNAs were differentially
      expressed by greater than two-fold, whilst 14% and 11% of cDNAs in the respective
      libraries were differentially expressed by more than 15-fold. Amongst these were
      oestrogen-responsive cDNAs and expressed sequence tags. One such oestrogen
      responsive expressed sequence tag, M41, is transcribed from a gene located on
      chromosome 21q22.3, within an intron of a larger gene. The M41 gene contains
      oestrogen response elements, one of which is associated with alu repeats. M41
      mRNA is expressed at a statistically significantly higher level in human breast
      cancer specimens than in normal human breast and benign lesions. In carcinomas,
      its up-regulation is associated with the development of the malignant cell.

PMID- 12177778
TI  - Tissue distribution and differential expression of melanocortin 1 receptor, a
      malignant melanoma marker.
AB  - The melanocortin 1 receptor is a G-protein-coupled receptor, described to be
      expressed on melanomas and melanocytes. Subsequent RT-PCR studies demonstrated
      the presence of melanocortin 1 receptor mRNA in other tissues such as pituitary
      gland and testis. Previously, we have demonstrated that three HLA-A2 binding
      nonamer peptides derived from melanocortin 1 receptor can elicit peptide-specific
      CTL which can recognize target cells transfected with the melanocortin 1 receptor
      gene and MHC class I matched melanoma lines. The potential of targeting
      melanocortin 1 receptor in therapy and diagnosis will depend on a preferential
      expression of this receptor in the majority of primary and metastatic melanomas
      vs normal tissues. We tested a panel of melanomas, carcinomas and other cell
      lines for the presence of melanocortin 1 receptor, using two monoclonal
      antibodies. The receptor was detected in 83% of the tested melanoma cell lines
      but not in other carcinoma lines. Immunohistochemistry revealed a strong
      expression of melanocortin 1 receptor in all tested primary and metastatic
      melanomas, but also demonstrated low levels of expression in adrenal medulla,
      cerebellum, liver and keratinocytes. Flow cytometry studies showed that
      melanocortin 1 receptor was expressed in in vitro activated monocytes/macrophages
      and in the THP-1 monocytic leukaemia line at levels of about 1 in 3 to 1 in 5 of
      that found in melanomas. Peripheral blood-derived dendritic cells, also express
      melanocortin 1 receptor in vitro. This extensive analysis of melanocortin 1
      receptor tissue distribution may be of relevance not only for melanoma
      immunology, but also for research on the pathogenicity of inflammatory conditions
      in the skin and neurologic tissues. It remains to be seen if the over-expression
      of melanocortin 1 receptor in melanomas is sufficiently high to allow a
      'therapeutic window' to be exploited in cancer immunotherapy.

PMID- 12177780
TI  - High resolution chromosome 3p, 8p, 9q and 22q allelotyping analysis in the
      pathogenesis of gallbladder carcinoma.
AB  - Our recent genome-wide allelotyping analysis of gallbladder carcinoma identified
      3p, 8p, 9q and 22q as chromosomal regions with frequent loss of heterozygosity.
      The present study was undertaken to more precisely identify the presence and
      location of regions of frequent allele loss involving those chromosomes in
      gallbladder carcinoma. Microdissected tissue from 24 gallbladder carcinoma were
      analysed for PCR-based loss of heterozygosity using 81 microsatellite markers
      spanning chromosome 3p (n=26), 8p (n=14), 9q (n=29) and 22q (n=12) regions. We
      also studied the role of those allele losses in gallbladder carcinoma
      pathogenesis by examining 45 microdissected normal and dysplastic gallbladder
      epithelia accompanying gallbladder carcinoma, using 17 microsatellite markers.
      Overall frequencies of loss of heterozygosity at 3p (100%), 8p (100%), 9q (88%),
      and 22q (92%) sites were very high in gallbladder carcinoma, and we identified 13
      distinct regions undergoing frequent loss of heterozygosity in tumours. Allele
      losses were frequently detected in normal and dysplastic gallbladder epithelia.
      There was a progressive increase of the overall loss of heterozygosity frequency
      with increasing severity of histopathological changes. Allele losses were not
      random and followed a sequence. This study refines several distinct chromosome
      3p, 8p, 9q and 22q regions undergoing frequent allele loss in gallbladder
      carcinoma that will aid in the positional identification of tumour suppressor
      genes involved in gallbladder carcinoma pathogenesis.

PMID- 12177781
TI  - Reduced Fhit expression is associated with mismatch repair deficiency in human
      advanced colorectal carcinoma.
AB  - The Fragile Histidine Triad gene, encompassing the FRA3B fragile site at
      chromosome 3p14.2, is a candidate tumour suppressor gene involved in multiple
      tumour types including colorectal carcinomas. Recently, it has been reported that
      the Fragile Histidine Triad gene may be a target of damage in a fraction of
      mismatch deficient tumours. To explore this hypothesis, we analysed both Fragile
      histidine triad and mismatch repair protein (Msh2 and Mlh1) expression using
      immumohistochemical methods in 52 advanced colorectal carcinomas (19 well-, 17
      moderately-, and 16 poorly-differentiated). In addition, we examined whether the
      Fragile histidine triad and mismatch repair protein expression correlated with
      p53 expression and clinicopathological findings. Significant loss or reduction of
      Fragile histidine triad expression was noted in 18 of the 52 (34.6%) advanced
      colorectal carcinomas: 2 (10.5%) well-differentiated, 3 (17.6%) moderately
      differentiated, 13 (81.3%) poorly-differentiated carcinomas, the frequency being
      significantly higher in the latter than that in the former two (P<0.0001). Loss
      of mismatch repair protein (mainly, Mlh1) expression was detected in 21 of the 52
      (40.4%) colorectal carcinomas. Moreover, reduced Fragile histidine triad
      expression was significantly associated with absence of mismatch repair protein
      expression in the advanced colorectal carcinomas (P<0.0001). However, the Fragile
      histidine triad and mismatch repair protein expression was not significantly
      associated with p53 expression. These results suggested that reduced Fragile
      histidine triad expression might be correlated with mismatch repair expression,
      but not with p53 expression.

PMID- 12177782
TI  - Low frequency of somatic mutations in the FH/multiple cutaneous leiomyomatosis
      gene in sporadic leiomyosarcomas and uterine leiomyomas.
AB  - Germline mutations in the fumarate hydratase gene at 1q43 predispose to
      dominantly inherited skin and uterine leiomyomata and leiomyosarcomas. The
      enzyme, which is a component of the tricarboxylic acid cycle, acts as a tumour
      suppressor. To evaluate fumarate hydratase in respective sporadic tumours, we
      analysed a series of 26 leiomyosarcomas and 129 uterine leiomyomas (from 21
      patients) for somatic mutations in fumarate hydratase and allelic imbalance
      around 1q43. None of the 26 leiomyosarcomas harboured somatic mutations in
      fumarate hydratase. Fifty per cent of leiomysarcomas tested showed evidence of
      allelic imbalance at 1q, but this was not confined to the vicinity of fumarate
      hydratase. Only 5% (seven out of 129) of the leiomyomas showed allele imbalance
      at 1q42-q43 and no somatic mutations in fumarate hydratase were observed. Our
      findings indicate that mutations in fumarate hydratase do not play a major role
      in the development of sporadic leiomyosarcomas or uterine leiomyomas

PMID- 12177783
TI  - Molecular classification of selective oestrogen receptor modulators on the basis
      of gene expression profiles of breast cancer cells expressing oestrogen receptor
      alpha.
AB  - The purpose of this study was to classify selective oestrogen receptor modulators
      based on gene expression profiles produced in breast cancer cells expressing
      either wtERalpha or mutant(351)ERalpha. In total, 54 microarray experiments were
      carried out by using a commercially available Atlas cDNA Expression Arrays
      (Clontech), containing 588 cancer-related genes. Nine sets of data were generated
      for each cell line following 24 h of treatment: expression data were obtained for
      cells treated with vehicle EtOH (Control); with 10(-9) or 10(-8) M oestradiol;
      with 10(-6) M 4-hydroxytamoxifen; with 10(-6) M raloxifene; with 10(-6) M
      idoxifene, with 10(-6) M EM 652, with 10(-6) M GW 7604; with 5 x 10(-5) M
      resveratrol and with 10(-6) M ICI 182,780. We developed a new algorithm
      'Expression Signatures' to classify compounds on the basis of differential gene
      expression profiles. We created dendrograms for each cell line, in which branches
      represent relationships between compounds. Additionally, clustering analysis was
      performed using different subsets of genes to assess the robustness of the
      analysis. In general, only small differences between gene expression profiles
      treated with compounds were observed with correlation coefficients ranged from
      0.83 to 0.98. This observation may be explained by the use of the same cell
      context for treatments with compounds that essentially belong to the same class
      of drugs with oestrogen receptors related mechanisms. The most surprising
      observation was that ICI 182,780 clustered together with oestrodiol and
      raloxifene for cells expressing wtERalpha and clustered together with EM 652 for
      cells expressing mutant(351)ERalpha. These data provide a rationale for a more
      precise and elaborate study in which custom made oligonucleotide arrays can be
      used with comprehensive sets of genes known to have consensus and putative
      oestrogen response elements in their promoter regions.

PMID- 12177784
TI  - Keratinocyte stimulation of matrix metalloproteinase-1 production and
      proliferation in fibroblasts: regulation through mitogen-activated protein kinase
      signalling events.
AB  - Incubation of human dermal fibroblasts in keratinocyte-conditioned culture medium
      led to a 5.7-fold increase in the level of matrix metalloproteinase-1. Virtually
      all of the matrix metalloproteinase-1 - inducing activity could be related to
      agonists acting through members of the epidermal growth factor receptor family or
      to agonists acting through the interleukin-1 receptor. The same keratinocyte
      conditioned medium also induced a modest increase in fibroblast proliferation
      (approximately 1.8-fold). Growth-stimulating activity could be attributed to
      epidermal growth factor receptor (but not interleukin-1 receptor) function. In
      fibroblasts exposed to keratinocyte-conditioned medium, mitogen-activated protein
      kinase signalling through both the extracellular signal-related kinase pathway
      and p38 pathway occurred. When recombinant epidermal growth factor or recombinant
      interleukin-1beta were used as a control, they induced mitogen-activated protein
      kinase signalling consistent with the combined effects of epidermal growth factor
      receptor - specific and interleukin-1 receptor - specific agonists in
      keratinocyte-conditioned medium. Recombinant epidermal growth factor stimulated
      both matrix metalloproteinase-1 induction and proliferation while recombinant
      interleukin-1beta stimulated matrix metalloproteinase-1 elaboration but not
      fibroblast growth. An inhibitor of extracellular signal-related kinase pathway
      signalling (U0126) blocked induction of matrix metalloproteinase-1 production
      induced by keratinocyte-conditioned medium (as well as by epidermal growth factor
      or interleukin-1beta), and also inhibited proliferation. A p38 signalling
      inhibitor (SB203580) blocked matrix metalloproteinase-1 elaboration induced by
      keratinocyte-conditioned medium or interleukin-1beta, but did not inhibit matrix
      metalloproteinase-1 elaboration or cell growth induced by epidermal growth
      factor. These data indicate that keratinocyte-fibroblast interactions are
      mediated by multiple stimulating agents acting on specific receptors to induce
      signalling through different mitogen-activated protein kinase pathways leading to
      altered expression of key biological functions.

PMID- 12177785
TI  - The antitumour activity of 5,6-dimethylxanthenone-4-acetic acid (DMXAA) in TNF
      receptor-1 knockout mice.
AB  - 5,6-dimethylxanthenone-4-acetic acid, a novel antivascular anticancer drug, has
      completed Phase I clinical trial. Its actions in mice include tumour necrosis
      factor induction, serotonin release, tumour blood flow inhibition, and the
      induction of tumour haemorrhagic necrosis and regression. We have used mice with
      a targeted disruption of the tumour necrosis factor receptor-1 gene as recipients
      for the colon 38 carcinoma to determine the role of tumour necrosis factor
      signalling in the action of 5,6-dimethylxanthenone-4-acetic acid. The
      pharmacokinetics of 5,6-dimethylxanthenone-4-acetic acid, as well as the degree
      of induced plasma and tissue tumour necrosis factor, were similar in tumour
      necrosis factor receptor-1(-/-) and wild-type mice. However, the maximum
      tolerated dose of 5,6-dimethylxanthenone-4-acetic acid was considerably higher in
      tumour necrosis factor receptor-1(-/-) mice (>100 mg kg(-1)) than in wild-type
      mice (27.5 mg kg(-1)). The antitumour activity of 5,6-dimethylxanthenone-4-acetic
      acid (25 mg kg(-1)) was strongly attenuated in tumour necrosis factor receptor-1(
      /-) mice. However, the reduced toxicity in tumour necrosis factor receptor-1(-/-)
      mice allowed the demonstration that at a higher dose (50 mg kg(-1)), 5,6
      dimethylxanthenone-4-acetic acid was curative and comparable in effect to that of
      a lower dose (25 mg kg(-1)) in wild-type mice. The 5,6-dimethylxanthenone-4
      acetic acid -induced rise in plasma 5-hydroxyindoleacetic acid, used to reflect
      serotonin production in a vascular response, was larger in colon 38 tumour
      bearing than in non-tumour bearing tumour necrosis factor receptor-1(-/-) mice,
      but in each case the response was smaller than the corresponding response in wild
      type mice. The results suggest an important role for tumour necrosis factor in
      mediating both the host toxicity and antitumour activity of 5,6
      dimethylxanthenone-4-acetic acid, but also suggest that tumour necrosis factor
      can be replaced by other vasoactive factors in its antitumour action, an
      observation of relevance to current clinical studies.

PMID- 12177787
TI  - Differences in efficacy found in animals between recombinant forms of
      erythropoietin will not necessarily translate into differences in humans.

PMID- 12177786
TI  - Delta-Aminolevulinic acid transport in murine mammary adenocarcinoma cells is
      mediated by beta transporters.
AB  - Delta-aminolevulinic acid, the precursor of porphyrin biosynthesis has been used
      to induce the endogenous synthesis of the photosensitiser protoporphyrin IX for
      photodynamic therapy in the treatment of various tumours. The aim of this work
      was to characterise the delta-aminolevulinic acid transport system in the murine
      mammary adenocarcinoma cell line LM3 using (14)C-delta-aminolevulinic acid, to
      finally improve delta-aminolevulinic acid incorporation in mammalian cells. Our
      results showed that delta-aminolevulinic acid is incorporated into these cells by
      two different mechanisms, passive diffusion which is important at the beginning
      of the incubation, and active transport. Specificity assays suggested that the
      transporter involved in delta-aminolevulinic acid incorporation is a BETA
      transporter, probably GAT-2.

PMID- 12177790
TI  - Protein expression profiles indicative for drug resistance of non-small cell lung
      cancer.
AB  - Data obtained from multiple sources indicate that no single mechanism can explain
      the resistance to chemotherapy exhibited by non-small cell lung carcinomas. The
      multi-factorial nature of drug resistance implies that the analysis of comprising
      expression profiles may predict drug resistance with higher accuracy than single
      gene or protein expression studies. Forty cellular parameters (drug resistance
      proteins, proliferative, apoptotic, and angiogenic factors, products of proto
      oncogenes, and suppressor genes) were evaluated mainly by immunohistochemistry in
      specimens of primary non-small cell lung carcinoma of 94 patients and compared
      with the response of the tumours to doxorubicin in vitro. The protein expression
      profile of non-small cell lung carcinoma was determined by hierarchical cluster
      analysis and clustered image mapping. The cluster analysis revealed three
      different resistance profiles. The frequency of each profile was different (77,
      14 and 9%, respectively). In the most frequent drug resistance profile, the
      resistance proteins P-glycoprotein/MDR1 (MDR1, ABCB1), thymidylate-synthetase,
      glutathione-S-transferase-pi, metallothionein, O6-methylguanine-DNA
      methyltransferase and major vault protein/lung resistance-related protein were up
      regulated. Microvessel density, the angiogenic factor vascular endothelial growth
      factor and its receptor FLT1, and ECGF1 as well were down-regulated. In addition,
      the proliferative factors proliferating cell nuclear antigen and cyclin A were
      reduced compared to the sensitive non-small cell lung carcinoma. In this
      resistance profile, FOS was up-regulated and NM23 down-regulated. In the second
      profile, only three resistance proteins were increased (glutathione-S-transferase
      pi, O6-methylguanine-DNA-methyltransferase, major vault protein/lung resistance
      related protein). The angiogenic factors were reduced. In the third profile, only
      five of the resistance factors were increased (MDR1, thymidylate-synthetase,
      glutathione-S-transferase-pi, O6-methylguanine-DNA-methyltransferase, major vault
      protein/lung resistance-related protein).

PMID- 12177792
TI  - The systemic inflammatory response, weight loss, performance status and survival
      in patients with inoperable non-small cell lung cancer.
AB  - The relationship between the magnitude of systemic inflammatory response and the
      nutritional/functional parameters in patients with inoperable non-small cell lung
      cancer were studied. The extent of weight loss, albumin, C-reactive protein,
      performance status and quality of life was measured in 106 patients with
      inoperable non-small cell lung cancer (stages III and IV). Survival analysis was
      performed using the Cox proportional hazard model. The majority of patients were
      male and almost 80% had elevated circulating C-reactive protein concentrations
      (>10 mg x l(-1)). On multivariate analysis, age (P=0.012), tumour type (0.002),
      weight loss (P=0.056), C-reactive protein (P=0.047), Karnofsky performance status
      (P=0.002) and fatigue (P=0.046) were independent predictors of survival. The
      patients were grouped according to the magnitude of the C-reactive protein
      concentrations (< or =10, 11-100 and >100 mg x l(-1)). An increase in the
      magnitude of the systemic inflammatory response was associated with increased
      weight loss (P=0.004), reduced albumin concentrations (P=0.001), reduced
      performance status (P=0.060), increased fatigue (P=0.011) and reduced survival
      (HR 1.936 95%CI 1.414-2.650, P<0.001). These results indicate that the majority
      of patients with inoperable non-small cell lung cancer have evidence of a
      systemic inflammatory response. Furthermore, an increase in the magnitude of the
      systemic inflammatory response resulted in greater weight loss, poorer
      performance status, more fatigue and poorer survival.

PMID- 12177791
TI  - Dose-escalation study of weekly irinotecan and daily carboplatin with concurrent
      thoracic radiotherapy for unresectable stage III non-small cell lung cancer.
AB  - Dose-escalation study was performed to evaluate the maximum tolerated dose,
      recommended dose and toxicity profile of weekly irinotecan with daily carboplatin
      and concurrent thoracic radiotherapy in patients with locally advanced non-small
      cell lung cancer. Thirty-one previously untreated patients with unresectable
      stage III non-small-cell lung cancer were enrolled in this study. Patients
      received weekly irinotecan plus carboplatin (20 mg x m(-2) daily for 5 days a
      week) for 4 weeks and thoracic radiotherapy (60 Gy in 30 fractions). The
      irinotecan dose was escalated from 30 mg x m(-2) in increments of 10 mg x m(-2).
      Four irinotecan dose levels were given and 30 patients were assessable. Their
      median age was 62 years (range: 52-72 years), 28 had a performance status of 0-1
      and two had a performance status of 2, 12 had stage IIIA disease and 18 had IIIB
      disease. There were 19 squamous cell carcinomas, 10 adenocarcinomas, and one
      large cell carcinoma. The dose-limiting toxicities were pneumonitis, esophagitis,
      thrombocytopenia and neutropenia. The maximum tolerated dose of irinotecan was 60
      mg x m(-2), with two patients developing grade 4 pulmonary toxicity and one
      patient died of pneumonitis (grade 5). The recommended dose of irinotecan was 50
      mg x m(-2). Other grade 3 or 4 toxicities were nausea and vomiting. Three
      patients achieved complete remission and 15 had partial remission, for an
      objective response rate of 60.0%. The median survival time was 14.9 months, and
      the 1- and 2-year survival rates were 51.6% and 34.2%, respectively. The study
      concluded that the major toxicity of this regimen was pneumonitis. This therapy
      may be active against unresectable non-small-cell lung cancer and a phase II
      study is warranted.

PMID- 12177793
TI  - Darbepoetin alfa given every 1 or 2 weeks alleviates anaemia associated with
      cancer chemotherapy.
AB  - In part A of this study, patients were randomised to cohorts receiving
      darbepoetin alfa at doses of 0.5 to 8.0 m.c.g x kg(-1) x wk(-1) or to a control
      group receiving epoetin alfa at an initial dose of 150 U x kg(-1) three times
      weekly. In part B, the cohorts were darbepoetin alfa 3.0 to 9.0 m.c.g x kg(-1)
      every 2 weeks or epoetin alfa, initial dose 40 000 U x wk(-1). Safety was
      assessed by adverse events, changes in blood pressure, and formation of
      antibodies to darbepoetin alfa. Efficacy was assessed by several haematologic
      endpoints, including change in haemoglobin from baseline. The adverse event
      profile of darbepoetin alfa was similar to that of epoetin alfa. No relationship
      between the rapidity of haemoglobin response and any adverse event was observed.
      No antibodies to darbepoetin alfa were detected. Higher doses of darbepoetin alfa
      increased the proportion of patients with a haemoglobin response and decreased
      the median time to response. The overall dose of darbepoetin alfa required to
      produce a mean increase in haemoglobin does not increase when the dosing interval
      is increased from 1 to 2 weeks. Therapy with darbepoetin alfa is safe and
      effective in producing a dose-related increase in haemoglobin levels in patients
      with cancer receiving chemotherapy.

PMID- 12177794
TI  - Hepatic cytochrome P450 3A drug metabolism is reduced in cancer patients who have
      an acute-phase response.
AB  - Inflammatory disease states (infection, arthritis) are associated with reduced
      drug oxidation by the cytochrome P450 3A system. Many chemotherapy agents are
      metabolised through this pathway, and disease may therefore influence inter
      individual differences in drug pharmacokinetics. The purpose of this study was to
      assess cytochrome P450 3A function in patients with advanced cancer, and its
      relation to the acute-phase response. We evaluated hepatic cytochrome P450 3A
      function in 40 patients with advanced cancer using the erythromycin breath test.
      Both the traditional C(20min) measure and the recently proposed 1/T(MAX) values
      were estimated. The marker of acute-phase response, C-reactive protein and the
      pro-inflammatory cytokines IL-6, IL-1beta, TNFalpha and IL-8 were measured in
      serum or plasma at baseline. Cancer patients with an acute phase response (C
      reactive protein >10 mg x l(-1), n=26) had reduced metabolism as measured with
      the erythromycin breath test 1/T(MAX) (Kruskal-Wallis Anova, P=0.0062) as
      compared to controls (C-reactive protein < or =10 mg x l(-1), n=14) Indeed,
      metabolism was significantly associated with C-reactive protein over the whole
      concentration range of this acute-phase marker (r=-0.64, Spearman Rank
      Correlation, P<0.00001). C-reactive protein serum levels were significantly
      correlated with those of IL-6 (Spearman coefficient=0.58, P<0.0003). The
      reduction in cytochrome P450 3A function with acute-phase reaction was
      independent of the tumour type and C-reactive protein elevation was associated
      with poor performance status. This indicates that the sub-group of cancer
      patients with significant acute-phase response have compromised drug metabolism,
      which may have implications for the safety of chemotherapy in this population.

PMID- 12177796
TI  - Pregnancy related protection against breast cancer depends on length of
      gestation.
AB  - In a prospective study of 694 657 parous women in Norway, 5474 developed breast
      cancer after their first birth. If the first pregnancy lasted less than 32 weeks,
      the risk was 22% (95% confidence interval, -3% to 53%) less than after a
      pregnancy of 40 weeks or more, with a significant declining trend in risk (P for
      trend=0.02).

PMID- 12177795
TI  - Predictors of long-term outcome following high-dose chemotherapy in high-risk
      primary breast cancer.
AB  - We report on a predictive model of long-term outcome in 114 high-risk breast
      cancer patients treated with high-dose chemotherapy between 1989 and 1994.
      Paraffin-blocks from 90 of the 114 primaries were assessed for the presence of
      five risk factors: grade, mitotic index, protein expression of p53, HER2/neu, and
      oestrogen/progesterone receptor status; we could analyse the effect of risk
      factors in 84 of these 90 tumours. Seven-year relapse-free and overall survival
      was 58% (95% confidence interval 44-74%) and 82% (95% confidence interval 71-94%)
      vs 33% (95% confidence interval 21-52%) and 41% (95% confidence interval 28-60%)
      for patients whose primary tumours displayed > or =3 risk factors vs patients
      with < or =2 risk factors. For the entire group of 168 high-risk breast cancer
      patients, inflammatory stage IIIB disease and involved post-mastectomy margins
      were associated with decreased relapse-free survival and overall survival;
      patients treated with non-doxorubicin containing standard adjuvant therapy
      experienced worse overall survival (RR, 2.08; 95% confidence interval 1.04 to
      4.16; P=0.04), while adjuvant tamoxifen improved overall survival (RR, 0.65; 95%
      confidence interval 0.41-1.01; P=0.054). Future trial designs and patient
      selection for studies specific for high-risk breast cancer patients should
      include appropriate prognostic models. Validation of such models could come from
      recently completed randomised, prospective trials.

PMID- 12177797
TI  - Trends in mortality from Hodgkin's disease in western and eastern Europe.
AB  - Hodgkin's disease mortality rates steadily declined by about 75% between the late
      1960's and the late 1990's in the current European Union countries and the USA,
      and Japan. Eastern European countries, however, showed only an approximately 40%
      decline between the late 1960's and the early 1990's, and no further fall
      thereafter.

PMID- 12177798
TI  - Heritable breast cancer in twins.
AB  - Known major mutations such as BRCA1/2 and TP53 only cause a small proportion of
      heritable breast cancers. Co-dominant genes of lower penetrance that regulate
      hormones have been thought responsible for most others. Incident breast cancer
      cases in the identical (monozygotic) twins of representative cases reflect the
      entire range of pertinent alleles, whether acting singly or in combination.
      Having reported the rate in twins and other relatives of cases to be high and
      nearly constant over age, we now examine the descriptive and histological
      characteristics of the concordant and discordant breast cancers occurring in 2310
      affected pairs of monozygotic and fraternal (dizygotic) twins in relation to
      conventional expectations and hypotheses. Like other first-degree relatives,
      dizygotic co-twins of breast cancer cases are at higher than usual risk
      (standardised incidence ratio (SIR)=1.7, CI=1.1-2.6), but the additional cases
      among monozygotic co-twins of cases are much more numerous, both before and after
      menopause (SIR=4.4, CI=3.6-5.6), than the 100% genetic identity would predict.
      Monozygotic co-twin diagnoses following early proband cancers also occur more
      rapidly than expected (within 5 years, SIR=20.0, CI=7.5-53.3). Cases in
      concordant pairs represent heritable disease and are significantly more likely to
      be oestrogen receptor-positive than those of comparable age from discordant
      pairs. The increase in risk to the monozygotic co-twins of cases cannot be
      attributed to the common environment, to factors that cumulate with age, or to
      any aggregate of single autosomal dominant mutations. The genotype more plausibly
      consists of multiple co-existing susceptibility alleles acting through heightened
      susceptibility to hormones and/or defective tumour suppression. The resultant
      class of disease accounts for a larger proportion of all breast cancers than
      previously thought, with a rather high overall penetrance. Some of the biological
      characteristics differ from those of breast cancer generally.

PMID- 12177799
TI  - The epidemiology of conjunctival squamous cell carcinoma in Uganda.
AB  - As part of a larger investigation of cancer in Uganda, we conducted a case
      control study of conjunctival squamous cell carcinoma in adults presenting at
      hospitals in Kampala. Participants were interviewed about social and lifestyle
      factors and had blood tested for antibodies to HIV, KSHV and HPV-16, -18 and -45.
      The odds of each factor among 60 people with conjunctival cancer was compared to
      that among 1214 controls with other cancer sites or types, using odds ratios,
      estimated with unconditional logistic regression. Conjunctival cancer was
      associated with HIV infection (OR 10.1, 95% confidence intervals [CI] 5.2-19.4;
      P<0.001), and was less common in those with a higher personal income (OR=0.4, 95%
      CI 0.3-0.7; P<0.001)[corrected]. The risk of conjunctival cancer increased with
      increasing time spent in cultivation and therefore in direct sunlight (chi2
      trend=3.9, P=0.05), but decreased with decreasing age at leaving home (chi2
      trend=3.9, P=0.05), perhaps reflecting less exposure to sunlight consequent to
      working in towns, although both results were of borderline statistical
      significance. To reduce confounding, sexual and reproductive variables were
      examined among HIV seropositive individuals only. Cases were more likely than
      controls to report that they had given or received gifts for sex (OR 3.5, 95% CI
      1.2-10.4; P=0.03), but this may have been a chance finding as no other sexual or
      reproductive variable was associated with conjunctival cancer, including the
      number of self-reported lifetime sexual partners (P=0.4). The seroprevalence of
      antibodies against HPV-18 and -45 was too low to make reliable conclusions. The
      presence of anti-HPV-16 antibodies was not significantly associated with squamous
      cell carcinoma of the conjunctiva (OR 1.5, 95% CI 0.5-4.3; P=0.5) and nor were
      anti-KSHV antibodies (OR 0.9, 95% CI 0.4-2.1; P=0.8). The 10-fold increased risk
      of conjunctival cancer in HIV infected individuals is similar to results from
      other studies. The role of other oncogenic viral infections is unclear.

PMID- 12177800
TI  - A prospective study of stomach cancer death in relation to green tea consumption
      in Japan.
AB  - To evaluate whether green tea consumption provides protection against stomach
      cancer death, relative risks were calculated using Cox proportional hazards
      regression analysis in the Japan Collaborative Study for Evaluation of Cancer
      Risk, sponsored by the Ministry of Health and Welfare (JACC Study). The study was
      based on 30 370 men and 42 481 women aged 40-79. After adjustment for age,
      smoking status, history of peptic ulcer, family history of stomach cancer along
      with certain dietary items, the risks associated with drinking one or two, three
      or four, five to nine, and 10 or more cups of green tea per day, relative to
      those of drinking less than one cup per day, were 1.6 (95% CI: 0.9-2.9), 1.1 (95%
      CI: 0.6-1.9), 1.0 (95% CI: 0.5-2.0), and 1.0 (95% CI: 0.5-2.0), respectively, in
      men (P for trend=0.669), and 1.1 (95% CI: 0.5-2.5), 1.0 (95% CI: 0.5-2.5), 0.8
      (95% CI: 0.4-1.6), and 0.8 (95% CI: 0.3-2.1), respectively, in women (P for
      trend=0.488). We found no inverse association between green tea consumption and
      the risk of stomach cancer death.

PMID- 12177801
TI  - Hepatitis B and C virus prevalence in a rural area of South Korea: the role of
      acupuncture.
AB  - A cross-sectional study evaluated the prevalence of and the risk factors for
      hepatitis C and B viruses among 700 adults above the age of 40 years in a rural
      area of South Korea. Seropositivity for hepatitis C virus antibody (11.0%, 95%
      confidence interval: 8.7-13.6) was higher than that for hepatitis B surface
      antigen (4.4%, 95% confidence interval: 3.0-6.2). Anti-hepatitis C virus
      seropositivity was associated with a history of repeated acupuncture (odds
      ratio=2.1, 95% confidence interval: 1.1-4.0), and blood transfusion (odds
      ratio=5.5, 95% confidence interval: 1.6-19.3) before 1992 when hepatitis C virus
      screening in blood donors became mandatory. Hepatitis C virus 2a was the most
      prevalent genotype, followed by 1b. Hepatitis C virus risk attributable to
      acupuncture was 38% (9% for men and 55% for women). Safer acupuncture practice
      has become a priority for hepatitis C virus prevention in South Korea.

PMID- 12177802
TI  - Reduced apoptotic levels in squamous but not basal cell carcinomas correlates
      with detection of cutaneous human papillomavirus.
AB  - We have investigated the apoptotic levels and expression of the apoptotic inducer
      Bak in non-melanoma skin cancers. Squamous cell carcinomas of known human
      papillomavirus status from immunocompetent patients were analysed for the
      expression of the Bak protein, and the expression profile was compared both to
      the presence of apoptotic cells and the proliferation marker Ki-67. We
      demonstrate an inverse correlation between human papillomavirus positivity and
      Bak expression in squamous cell carcinomas, with concomitantly fewer apoptoic
      cells being detected in the human papillomavirus positive tumours. Bak expression
      was not observed in basal cell carcinomas irrespective of human papillomavirus
      status, suggesting that Bak only plays a role in signalling apoptosis in
      squamous, but not basal, cell cancers. No differences were observed in the
      proliferation rates between papillomavirus positive and negative squamous cell
      tumours. However, a significant decrease in the number of apoptotic cells was
      observed in human papillomavirus-positive squamous cell carcinomas which suggests
      that the virus may have significantly altered the relationship between
      proliferation and apoptosis in a proportion of these tumours.

PMID- 12177803
TI  - Prevalence and determinants of HPV infection among Colombian women with normal
      cytology.
AB  - Human papillomavirus is the principal risk factor associated with cervical
      cancer, the most common malignancy among women in Colombia. We conducted a
      survey, aiming to report type specific prevalence and determinants of human
      papillomavirus infection in women with normal cytology. A total of 1859 women
      from Bogota, Colombia were interviewed and tested for human papillomavirus using
      a general primer GP5+/GP6+ mediated PCR-EIA. The overall HPV DNA prevalence was
      14.8%; 9% of the women were infected by high risk types, 3.1% by low risk types,
      2.3% by both high risk/low risk types and 0.4% by uncharacterized types (human
      papillomavirus X). Thirty-two different human papillomavirus types were detected,
      being human papillomavirus 16, 58, 56, 81(CP8304) and 18 the most common types.
      The human papillomavirus prevalence was 26.1% among women younger than 20 years,
      2.3% in women aged 45-54 years, and 13.2% in women aged 55 years or more. For low
      risk types the highest peak of prevalence was observed in women aged 55 years or
      more. Compared to women aged 35-44 years, women aged less than 20 years had a 10
      fold increased risk of having multiple infections. Besides age, there was a
      positive association between the risk of human papillomavirus infection and
      number of regular sexual partners and oral contraceptive use. In women aged below
      25 years, high educational level and having had casual sexual partners predicted
      infection risk. In conclusion, there was a broad diversity of human
      papillomavirus infections with high risk types being the most common types
      detected. In this population multiplicity of sexual partners and, among young
      women, high educational level and casual sexual partners seem to determine risk.

PMID- 12177804
TI  - Effect of neoadjuvant treatment with anastrozole on tumour histology in
      postmenopausal women with large operable breast cancer.
AB  - Anastrozole is an orally active, non-steroidal aromatase inhibitor which appears
      effective as neoadjuvant treatment of breast cancer. Histological changes have
      been evaluated in biopsies from large, oestrogen-receptor rich, operable breast
      tumours in postmenopausal women following 12 weeks of neoadjuvant anastrozole
      treatment (1 mg (n=12) or 10 mg (n=11)). Of the 23 patients, 18 had a clinical
      response following treatment. Compared with pre-treatment biopsies anastrozole
      treated specimens displayed decreased cellularity and/or increased fibrosis in 15
      tumours; changes in gland formation, nuclear pleomorphism, or mitoses, in 12
      cases; and a reduction in Mib1 score in all tumours. Marked changes in apoptotic
      scores were seen following treatment but the direction of effect was
      inconsistent. In all 17 tumours which were positive for progesterone receptors
      before therapy, treatment was associated with reduced staining for progesterone
      receptors. There was no consistent effect of treatment on oestrogen-receptor
      expression. It is concluded that neoadjuvant anastrozole treatment in this
      patient group has marked effects on tumour histopathology but these do not always
      correlate with clinical response.

PMID- 12177805
TI  - Identification of heat shock protein 90 and other proteins as tumour antigens by
      serological screening of an ovarian carcinoma expression library.
AB  - Serological screening of recombinant cDNA expression libraries has been widely
      used for the identification of tumour antigens in various cancer types.
      Identification of tumour antigens in ovarian cancer may facilitate the
      development of vaccine-based therapies and of disease biomarkers. The purpose of
      our investigation is to identify tumour antigens in ovarian cancer by using the
      serological analysis of recombinant cDNA expression libraries method. A
      recombinant ovarian carcinoma cDNA expression library was screened with ascites
      fluid, pooled from five ovarian cancer patients. Twelve tumour antigens encoded
      by known genes were isolated, including ribosomal protein S18, heat shock protein
      90, JK-recombination signal binding protein, ribonucleoprotein H1, RAN binding
      protein 7, TG-interacting factor, eukaryotic translation initiation factor p40
      subunit, human amyloid precursor protein-binding protein 1, ribosomal protein L8,
      CDC23, IQ motif containing GTPase activating protein 1, and ribosomal protein L3.
      Heat shock protein 90 was chosen for further investigation. The prevalence of
      hsp90 autoantibodies in ovarian cancer was determined with immunoassay. Sera from
      22 normal females, 32 from ovarian cancer (22 stage III/IV, 10 stage I/II), 37
      colorectal cancer, 13 breast cancer, 10 lung cancer, 20 benign gynaecologic
      diseases, and 10 benign breast lesions were screened. Seven (32%) stage III/IV
      ovarian cancer, 1 (10%) stage I/II ovarian cancer, 1 (3%) colorectal cancer, 1
      (8%) breast cancer, and 1 (5%) benign gynaecologic disease sera were found to
      contain hsp90 autoantibodies. These data support the view that hsp90
      autoantibodies are frequently found in late stage ovarian cancer. Hsp90 may,
      therefore, represent a novel biomarker for ovarian cancer and a candidate ovarian
      cancer vaccine target.

PMID- 12177806
TI  - Flow cytometric quantification of tumour endothelial cells; an objective
      alternative for microvessel density assessment.
AB  - Assessment of microvessel density by immunohistochemical staining is subject to a
      considerable inter-observer variation, and this has led to variability in
      correlation between microvessel density and clinical outcome in different
      studies. In order to improve the method of microvessel density measurement in
      tumour biopsies, we have developed a rapid, objective and quantitative method
      using flow cytometry on frozen tissues. Frozen tissue sections of archival tumour
      material were enzymatically digested. The single-cell suspension was stained for
      CD31 and CD34 for flow cytometry. The number of endothelial cells was quantified
      using light scatter- and fluorescence-characteristics. Tumour endothelial cells
      were detectable in a single cell suspension, and the percentage of endothelial
      cells detected in 32 colon carcinomas correlated highly (r=0.84, P<0.001) with
      the immunohistochemical assessment of microvessel density. Flow cytometric
      endothelial cells quantification was found to be more sensitive especially at
      lower levels of immunohistochemical microvessel density measurement. The current
      method was found to be applicable for various tumour types and has the major
      advantage that it provides a retrospective and quantitative approach to the
      angiogenic potential of tumours.

PMID- 12177807
TI  - Integrin alpha(v)beta6-associated ERK2 mediates MMP-9 secretion in colon cancer
      cells.
AB  - There is general consensus that matrix metalloproteinases are involved in tumour
      progression. We show herein that inhibition of integrin alpha(v)beta6 expression
      in colon cancer cells suppresses MMP-9 secretion. This integrin-mediated event is
      dependent upon direct binding between the beta6 integrin subunit and
      extracellular signal-regulated kinase 2. Targetting either beta6 or its
      interaction with extracellular signal-regulated kinase in order to inhibit matrix
      metalloproteinase activity may offer a useful therapeutic approach in preventing
      growth and spread of colon cancer.

PMID- 12177809
TI  - Granulocytes mediates the Fas-L-associated apoptosis during lung metastasis of
      melanoma that determines the metastatic behaviour.
AB  - The survival of tumour cells in a new tissue environment is crucial for tumour
      metastasis. Factors contributing to the death of tumour cells during metastasis
      are not completely understood. In murine melanoma model, activation of Fas (CD95,
      APO-1) signal in tumour cells reduces their lung metastasis potential, which may
      be associated with an induction of apoptosis in tumours. To elucidate the
      cellular mechanism, we used a Fas-ligand (Fas-L) specific ribozyme (Fas
      L(ribozyme)) to suppress the expression of Fas-L but not Fas or TNF-alpha in
      B16F10 melanoma cells. The Fas-L(ribozyme)-carrying cells grew slightly faster in
      vitro with better viability than controls. Suppression of Fas-L in B16F10
      melanoma cells by Fas-L(ribozyme) enhanced lung metastasis of the cells in
      C57BL/6 mice, and that was correlated with reductions in both apoptotic tumour
      cells and granulocytic infiltration. Mice depleted of granulocytes, but not CD4+
      and CD8+ cells, showed a greatly elevated susceptibility to lung metastasis.
      Moreover, apoptosis in tumour cells was significantly reduced in granulocyte
      depleted mice during the course of tumour formation. Taken together, our findings
      indicate that Fas-L-associated apoptosis in tumour cells determines the
      metastasis behaviour of melanoma in the lung and this apoptosis is primarily
      mediated by the cytotoxicity of recruited granulocytes.

PMID- 12177808
TI  - Abrogation of the radiation-induced G2 checkpoint by the staurosporine derivative
      UCN-01 is associated with radiosensitisation in a subset of colorectal tumour
      cell lines.
AB  - Ionising radiation is commonly used in the treatment of colorectal cancer. Tumour
      cells with mutant p53 undergo cell cycle arrest at G2/M after ionising radiation
      and evidence suggests that abrogation of this G2 arrest can lead to a premature,
      aberrant mitosis, thus enhancing ionising radiation-induced cell killing. The G2
      checkpoint inhibitor UCN-01 was thus investigated to determine whether it would
      abrogate the G2 checkpoint induced by 5 Gy ionising radiation in a range of
      colorectal tumour cell lines. Data presented show that, at doses that are alone
      non-toxic to the cells, UCN-01 inhibits the ionising radiation-induced G2
      checkpoint in five colorectal tumour cell lines with mutant p53. The ability of
      UCN-01 to sensitise cells to ionising radiation-induced growth inhibition and
      apoptosis was also investigated and UCN-01 was found to radiosensitise two out of
      five cell lines. These results were confirmed by long-term colony forming
      efficiency studies. These results demonstrate that abrogation of the ionising
      radiation-induced G2 checkpoint is not necessarily associated with sensitisation
      to ionising radiation, however, some colorectal tumour cell lines can be
      radiosensitised by UCN-01. Although the mechanism of radiosensitisation is not
      clear, this may still be an important treatment strategy.

PMID- 12177810
TI  - The bisphosphonate pamidronate induces apoptosis in human melanoma cells in
      vitro.
AB  - Pamidronate belongs to the class of nitrogen-containing bisphosphonates that are
      potent inhibitors of bone resorption frequently used for the treatment of
      osteoporosis and cancer-induced osteolysis. The inhibition of osteoclasts' growth
      has been suggested as the main mechanism of the inhibitory effect of pamidronate
      on bone metastases. Recent findings indicated that bisphosphonates also have a
      direct apoptotic effect on other types of tumour cells. Nitrogen-containing
      bisphosphonates were shown to inhibit farnesyl diphosphate synthase, thus
      blocking the synthesis of higher isoprenoids. By this mechanism they inactivate
      monomeric G-proteins of the Ras and Rho families for which prenylation is a
      functional requirement. On the background of the known key role of G-proteins in
      tumorigenesis, we investigated a possible beneficial use of pamidronate in the
      treatment of malignant melanoma. Our results indicate that pamidronate inhibits
      the cell growth and induces apoptosis in human melanoma cells in vitro.
      Susceptibility to pamidronate did not correlate to CD95 ligand sensitivity or p53
      mutational status. Furthermore it is interesting to note that overexpression of
      bcl-2 did not abolish pamidronate-induced apoptosis. These data suggests that
      pamidronate has a direct anti-tumour effect on malignant melanoma cells,
      independently of the Bax/Bcl-2 level.

PMID- 12177812
TI  - Distal anterior interosseous nerve transfer to the deep motor branch of the ulnar
      nerve for reconstruction of high ulnar nerve injuries.
AB  - Proximal ulnar nerve injuries can result in loss of intrinsic muscle function of
      the hand, and distal nerve transfers provide nerve coaptation close to the target
      muscle. This retrospective chart review evaluated patient outcome following a
      distal nerve transfer of the anterior interosseous nerve (AIN) to the deep motor
      branch of the ulnar nerve. There were eight patient charts reviewed, three women,
      and five men. The mean patient age was 38 years (standard deviation: 22 years).
      The mean time from injury to surgery was 3 months (standard deviation: 3 months),
      and mean postoperative follow-up time was 18 months (standard deviation: 11
      months). All patients had reinnervation of the ulnar nerve intrinsic hand muscles
      with improved postoperative lateral pinch and grip strength. One patient had a
      secondary tendon transfer. No functional deficit in performing tasks in pronation
      was reported. The distal nerve transfer of the AIN to the deep motor branch of
      the ulnar nerve provides good reinnervation of the ulnar-nerve-innervated
      intrinsic muscles of the hand.

PMID- 12177813
TI  - Free fibula flap-donor-site morbidity: case report and review of the literature.
AB  - The free osteocutaneous fibula flap is the most commonly transferred vascularized
      bone flap used today. The associated donor site morbidity is well-reported,
      including vague pain which usually presents late, and is associated with few
      objective clinical findings. The authors report a case in which the pain had an
      identifiable cause; they suggest how this can be avoided.

PMID- 12177817
TI  - Flying solo: a single year-single surgeon community hospital replantation/
      revascularization experience.
AB  - A recent 12-month review of the emergent replantation/revascularization
      experience of a solo practice microsurgeon in a community hospital environment is
      presented. A total of 67 digits and/or hands/limbs were operated on in 51
      patients with a success rate of 87 percent. There were nine failures, all in
      digits with crush-avulsion etiologies. These results support the position that
      the single microsurgeon practicing in a community hospital environment can
      provide levels of care for patients with amputated or devascularized digits and
      parts comparable to tertiary medical centers.

PMID- 12177815
TI  - Lengthening of replanted or revascularized lower limbs: is length discrepancy a
      contraindication for limb salvage?
AB  - Some replantation cases require substantial bone shortening for primary closure.
      Leg-length discrepancy can be restored by lengthening of the replanted or
      revascularized extremities. Between 1991 and 2000, four patients with four total
      and two subtotal below-knee amputations had replantation or revascularization for
      their severely damaged extremities. All of them had extensive debridement,
      vascular repair, bone shortening and nerve repair for sensibility of their soles.
      One of the replanted extremities failed and had to undergo below-knee amputation
      because of sepsis. No other infection or vascular complications were encountered
      following the replantations or revascularizations. After bony consolidation, four
      legs were lengthened; for elimination of length discrepancy in three cases, and
      for obtaining balanced body proportion in one case in which the other leg was
      also amputated. In all procedures, a unilateral dynamic axial external fixator
      was used. The lengthening was performed from the proximal tibial metaphysis, with
      a subperiosteal osteotomy. Evaluation of injury according to the Mangled
      Extremity Severity Score (MESS) would encourage the surgeon to avoid salvage
      surgery with a shortened extremity, because of the required debridement of soft
      tissue and bone. These authors think the amount of limb shortening is not a major
      criterion in evaluating a traumatic total or subtotal below-knee amputation for
      salvage replantation or revascularization. A knee that has stable joint motion
      and the possibility of preservation of sensibility of the sole broadens the scope
      of indications for limb salvage, even with deliberate shortening that can be
      restored by lengthening; length discrepancy is not a contraindication for limb
      salvage.

PMID- 12177818
TI  - Continuous free-flap monitoring with tissue-oxygen measurements: three-year
      experience.
AB  - Early recognition of flap failure is a prerequisite for flap salvage. Many
      methods are used to monitor free flaps. The time interval for re-establishing
      vascular patency is the limiting factor for a successful revision. Prompt re
      operation and a rapid and sufficient correction of the microvascular anastomosis
      are necessary to maintain flap viability. The Licox Catheter pO 2 Micro-Probe
      instrument is used for continuous determination of oxygen partial pressure (pO 2
      ) in body fluids and tissue (p ti O 2 ). Over a period of 3 years, 60 free tissue
      transfers to head and neck, trunk, and upper and lower extremities were monitored
      using the Licox Catheter Probe System. The flexible Licox Catheter pO 2 Micro
      Probe detected circulatory changes and failure in all cases, with no false
      positives or negatives. In all cases in which the arterial pedicle failed, the p
      ti O 2 dropped rapidly; in cases of venous insufficiency, the p ti O 2 value
      decreased more or less slowly. In all failing flaps, a p ti O 2 decrease of 10
      mmHg within a half-hour, or a p ti O 2 drop below 10 mmHg was observed. These are
      observations which are useful as precise indicators for vascular complications
      and flap failure. Based on the authors' observations and data, the Licox probe is
      a sensitive and accurate monitoring system for all types of free flaps.

PMID- 12177820
TI  - Peripheral nerve regeneration in the apolipoprotein-E-deficient mouse.
AB  - Apolipoprotein E (apo E) is thought to mediate the reutilization of myelin
      cholesterol for nerve regeneration. Prior research suggests that apo E is not
      essential for nerve regeneration following a nerve crush injury. This study was
      conducted to determine if apo E is essential for nerve regeneration after nerve
      transection and interposition nerve autograft. Nerve regeneration of transgenic
      apo E-deficient mice was compared with control mice after a sciatic nerve
      neurolysis and repair and interposition autograft. Histomorphometric assessment
      and histology were performed on distal nerve segments to evaluate nerve
      regeneration. Apo E-deficient mice demonstrated no difference in total fiber
      number or nerve fiber width when compared with controls; however, the nerve fiber
      density and percent neural tissue of apo E-deficient mice were significantly less
      than controls following nerve repair. Apo E deficiency does not affect nerve
      regeneration. It is likely that the low nerve fiber density and the low percent
      neural tissue associated with apo E-deficiency result from impairment in the
      disposal of myelin debris.

PMID- 12177821
TI  - Extended rat-ear flap model: a new rodent model for studying the effects of
      vessel supercharging on flap viability.
AB  - A new extended rat-ear flap model, with both an axial and a random component, is
      described. The flap is based on an axial supply by the posterior auricular artery
      and the posterior facial vein. The random portion, consisting of the rat dorsum,
      is capable of being supercharged at two separate sites-in the scapular and pelvic
      regions. There are several advantages to this composite flap. It is a combined
      axial and random flap. When used as a free flap, the viability of the axial
      portion serves as an indicator for anastomotic patency. The random portion allows
      for the investigation of the effects of pharmaceutical manipulation or surgical
      intervention, e.g., flap supercharging. The results indicate that the axial
      supply alone can cover approximately 50 percent of the extended rat-ear flap.
      Moreover, adding supercharging perforators to the random portion significantly
      increases the area of flap survival. Of interest, an axial vascular supply,
      coupled with more distal dorsal perforators (pelvic) than proximal (scapular)
      perforators, may increase survival for the so-called "watershed" area in the
      middle of the random portion of the flap. Additionally, this study also
      investigated the relative importance of arterial supply vs. venous drainage,
      using the extended rat-ear flap model. The flap was either supercharged with both
      the perforators of the scapular and pelvic arteries, or both scapular and pelvic
      veins. The results of the study suggests that augmenting venous drainage provides
      statistically significant improvement (87 percent vs. 51.6 percent) in increasing
      flap survival, when compared to augmenting the arterial supply. Arterial
      supercharging provided no improvement in flap survival, when compared to no
      supercharging (axial vessels + arterial supercharging, 51.6 percent vs. axial
      vessels alone, 49.9 percent). The results also suggest that providing adequate
      venous outflow is more important than providing additional arterial blood, and
      that impaired venous outflow may contribute to some cases of flap failure.
      However, it should be kept in mind that the best flap survival occurs with both
      arterial and and venous supercharging.

PMID- 12177822
TI  - Experimental study of polarity in reversing cable nerve grafts.
AB  - To evaluate the effect of cable nerve graft polarity, the bilateral common
      peroneal nerves in 12 rabbits were excised to create 20-mm nerve gaps. These gaps
      were repaired with cable grafts using three strands of 20-mm ipsilateral sural
      nerves. In the left leg, the sural nerves were grafted with the original
      orientation. In the right leg, the nerve graft polarity was reversed 180 degrees.
      Six months later, motor conduction velocities were evaluated, and the bilateral
      anterior tibial muscles and extensor digitorum longus muscles were measured. The
      nerves were harvested and analyzed histologically. Motor conduction velocity was
      37.4+/-4.1 m/s in the reversed group, and 36.6+/-5.5 m/s in the control group.
      The weight of the muscles was 7.2+/-0.8 g in the reversed orientation, and 7.0+/
      1.0 g in the original orientation. None of the differences was statistically
      significant. Histologically, the axon counts and the axonal density distal to the
      nerve graft also showed no differences between groups. The sural nerves used did
      not have a major branch and their diameter was almost the same throughout its
      length. Reversing nerve graft polarity of a cable graft did not affect nerve
      regeneration electrophysiologically or histologically.

PMID- 12177825
TI  - Ion regulatory patterns of mosquito larvae collected from breeding sites in the
      Amazon rain forest.
AB  - We examined the ion composition of mosquito breeding sites located in the Amazon
      rain forest and the ion regulatory patterns of larvae from these habitats. We
      found larvae of Toxorhynchites haemorroidalis, Limatus durhamii, Culex
      (Carrollia) bonnei, and Culex (Culex) sp. residing in fallen palm bracts, leaves,
      and tree holes that were filled with water. These breeding sites had micromolar
      levels of Na(+) (1.6-99 micromol L(-1)), but K(+) and Cl(-) concentrations were
      higher and varied over a large range (231-17,615 micromol L(-1) K(+); 355-2,700
      micromol L(-1) Cl(-)). Despite the variability in environmental ion levels and
      ratios, all four species maintain high hemolymph NaCl levels (80-120 mmol L(-1)
      Na(+); 60-80 mmol L(-1) Cl(-)). However, the species differed in the means by
      which they maintain hemolymph ion balance, as indicated by the range of
      unidirectional Na(+) and Cl(-) uptake rates. Toxorhynchites haemorroidalis had
      extremely low rates of Na(+) uptake and undetectable Cl(-) uptake, whereas L.
      durhamii had high rates of uptake for both ions. This variability in rates of
      uptake may reflect species differences in rates of diffusive ion loss (i.e.,
      permeability). We observed the same curious pattern of Na(+) inhibition and Cl(-)
      stimulation by low-pH exposure in all four species of mosquitoes, as has been
      documented in other mosquitoes and aquatic insects. Kinetic analyses of Na(+) and
      Cl(-) uptake in C. bonnei larvae revealed an unusual pattern of Na(+) uptake that
      increases linearly (nonsaturable) to extremely high rates, while Cl(-) uptake is
      a low-affinity, low-capacity system. This pattern contrasts with L. durhamii and
      Culex (Culex) sp. larvae, which had large increases in both Na(+) and Cl(-)
      uptake when external NaCl levels were increased. Our results suggest that
      although these rain forest mosquito larvae are residing in habitats with similar
      low Na(+), high Cl(-) composition and maintain similar hemolymph NaCl levels, the
      underlying mechanisms of ion regulation differ among the species.

PMID- 12177826
TI  - The characterization of ion regulation in Amazonian mosquito larvae: evidence of
      phenotypic plasticity, population-based disparity, and novel mechanisms of ion
      uptake.
AB  - This study is the first step in characterizing ion uptake mechanisms of mosquito
      larvae from the Amazon region of Brazil. Hemolymph NaCl levels and rates of
      unidirectional Na(+) and Cl(-) uptake were measured in larvae of Aedes aegypti
      and Culex quinquefasciatus in a series of environmental manipulations that are
      known to challenge ion regulation in other aquatic animals. Despite being reared
      for numerous generations in dilute media (20 micromol L(-1) NaCl), both species
      were able to maintain high hemolymph NaCl concentrations, a departure from
      previous studies. Exposure to distilled water or high-NaCl media did not affect
      hemolymph ion levels, but pH 3 caused significant decreases in hemolymph Na(+)
      and Cl(-) levels in both species. Exposure to water from Rio Negro (pH 5.5), an
      organically rich but ion-poor body of water, did not disturb hemolymph Na(+) and
      Cl(-) levels or the uptake of these ions. Acute exposure to control media or Rio
      Negro water titrated to pH 3.5 caused inhibition of Na(+) uptake and stimulation
      of Cl(-) uptake in C. quinquefasciatus, but A. aegypti larvae experienced only a
      significant reduction of Na(+) uptake in Rio Negro/pH 3.5 treatment. The
      stimulation of Cl(-) uptake at low pH has been documented only in aquatic insects
      and differs from all other invertebrate and vertebrate species. A similar pattern
      of Na(+) uptake inhibition and Cl(-) uptake stimulation was observed in A.
      aegypti larvae exposed to bafilomycin A(1), a blocker of V-type H(+) ATPase.
      Culex quinquefasciatus larvae were unaffected by this drug. Both Na(+) and Cl(-)
      uptake were reduced when C. quinquefasciatus larvae were exposed to
      acetazolamide, indicating that H(+) and HCO(3)(-), derived from hydration of
      CO(2), are involved with Na(+) and Cl(-) uptake. Kinetic analysis of Na(+) and
      Cl(-) uptake in C. quinquefasciatus, A. aegypti, and Anopheles nuneztovari larvae
      indicate that these Amazonian species share similar high-capacity and high
      affinity mechanisms. Comparison of the Amazonian C. quinquefasciatus with a
      Californian population provided evidence of both phenotypic plasticity and
      population disparity in Na(+) and Cl(-) uptake, respectively. When the California
      population of C. quinquefasciatus was reared in a medium similar to that of the
      Amazonian group (60 micromol L(-1) NaCl) instead of 4,000 micromol L(-1) NaCl,
      larvae increased both Na(+) uptake capacity (J(max)) and affinity (i.e., reduced
      K(m)), yet Cl(-) uptake did not change from its nonsaturating, low-capacity
      pattern. In the reverse experiment, Amazonian C. quinquefasciatus demonstrated
      plasticity in both Na(+) and Cl(-) uptake by significantly reducing rates when
      held in 4,000 micromol L(-1) NaCl for 3 d.

PMID- 12177827
TI  - Ionoregulatory changes in the gill epithelia of coho salmon during seawater
      acclimation.
AB  - Short-term exposure of coho salmon smolts (Oncorhynchus kisutch) to a gradual
      increase in salinity over 2 d (0 per thousand -32 per thousand ) resulted in a
      decrease in proton pump abundance, detected as changes in immunoreactivity with a
      polyclonal antibody against subunit A of bovine brain vacuolar H(+)-ATPase. N
      ethylmaleimide (NEM)-sensitive H(+)-ATPase activities in gill homogenates
      remained unchanged over 8 d to coincide with a 3.5-fold increase in Na(+)/K(+)
      ATPase activities. A transient increase in plasma [Na(+)] and [Cl(-)] levels over
      the 8-d period was preceded by a 10-fold increase in plasma cortisol levels,
      which peaked after 12 h. Long-term (1 mo) acclimation to seawater resulted in the
      loss of apical immunoreactivity for vH(+)-ATPase and band 3-like anion exchanger
      in the mitochondria-rich cells identified by high levels of Na(+)/K(+)-ATPase
      immunoreactivity. The polyclonal antibody Ab597 recognized a Na(+)/H(+) exchanger
      (NHE-2)-like protein in what appears to be an accessory cell (AC) type.
      Populations of these ACs were found associated with Na(+)/K(+)-ATPase rich
      chloride cells in both freshwater- and seawater-acclimated animals.

PMID- 12177828
TI  - Relating intramuscular fuel use to endurance in juvenile rainbow trout.
AB  - This study examined fuel depletion in white muscle of juvenile rainbow trout
      sprinted to fatigue to determine whether the onset of fatigue is associated with
      a measurable metabolic change within the muscle and whether muscle glycogen
      levels influence endurance. In this study, "fuels" refer to any energy-supplying
      compounds and include glycogen, phosphocreatine (PCr), and ATP. Fuel depletion in
      white muscle was estimated by the calculation of the anaerobic energy expenditure
      (AEE; in micromol ATP equivalents g(-1)) from the reduction of PCr and ATP and
      the accumulation of lactate. Progression of fuel use during sprinting was
      examined by sampling fish before they showed signs of fatigue and following
      fatigue. Most of the AEE before fatigue was due to PCr depletion. However, at the
      first signs of fatigue, there was a 32% drop in ATP. Similarly, when fish were
      slowly accelerated to a fatiguing velocity, the only significant change at
      fatigue was a 30% drop in ATP levels. Muscle glycogen levels were manipulated by
      altering ration (1% vs. 4% body weight ration per day) combined with either daily
      or no exercise. Higher ration alone led to significantly greater muscle glycogen
      but had no effect on sprint performance, whereas sprint training led to higher
      glycogen and an average threefold improvement in sprint performance. In contrast,
      periodic chasing produced a similar increase in glycogen but had no effect on
      sprint performance. Taken together, these observations suggest that (i) a
      reduction in ATP in white muscle could act as a proximate signal for fatigue
      during prolonged exercise in fish and (ii) availability of muscle glycogen does
      not limit endurance.

PMID- 12177829
TI  - Ontogeny of the pulmonary surfactant and antioxidant enzyme systems in the
      viviparous lizard, Tiliqua rugosa.
AB  - The antioxidant enzyme (AOE) system protects the lung from oxidative damage. The
      pulmonary surfactant (PS) system lowers the interfacial pressure within the lung,
      improving lung compliance and aiding lung clearance. In mammals, the AOE and PS
      systems develop in tandem during the final 10%-20% of gestation. Here, we
      investigated the development of these systems in the viviparous skink, Tiliqua
      rugosa. The content of total phospholipid (PL), disaturated phospholipid (DSP),
      and cholesterol (Chol) increased in lung washings from foetal lizards with
      advancing gestational age. Similarly, the relative saturation of the PLs
      increased throughout gestation, with mid-stage 40 foetuses having a DSP/PL
      equivalent to newborns and adults. Maternal lizards had significantly less total
      PL, DSP, and Chol than nongravid and newborn lizards; however, the relative
      composition did not differ from nongravid animals. This presumably results from
      compression of the lungs under the bulk of the developing foetus. The Chol/PL and
      Chol/DSP ratios declined early in development such that mid-stage 40 embryos had
      comparable ratios to both newborns and adults. Thus, it appears that the PS
      system matures in a similar manner in skinks and in mammals. However, the
      composition of surfactant is complete some weeks before parturition, probably to
      enable improved survivorship of the precocial young in the event of premature
      birth. Unlike the surfactant lipids, the AOEs, catalase, superoxide dismutase,
      and glutathione peroxidase did not differ appreciably throughout gestation. It
      appears therefore that like the surfactant lipids the AOE system is in readiness
      for air breathing throughout the latter stages of gestation, possibly in
      preparation for premature birth. Unlike mammals, the PS and AOE systems develop
      independently from one another.

PMID- 12177830
TI  - The influence of bacterial lipopolysaccharide on the thermoregulation of the box
      turtle Terrapene carolina.
AB  - Ectotherms can adjust their thermoregulatory set points in response to bacterial
      infection; the result may be similar to endothermic fever. We examined the
      influence of dose on the set point of body temperature (T(b)) in Terrapene
      carolina. After acclimating postprandial turtles to 20 degrees C, we injected
      them with two doses of bacterial endotoxin (LPS; lipopolysaccharide from
      Escherichia coli), 0.0025 or 0.025 mg LPS/g nonshell body mass, or with reptilian
      saline (control group). We placed the animals singly in linear thigmothermal
      gradients and recorded their T(b)'s for 48 h. The turtles showed dose-influenced
      thermal selection. Turtles injected with the high dose had T(b)'s significantly
      higher than control turtles, whereas low-dose turtles had T(b)'s significantly
      lower than control turtles. Also, there was a low daily effect on the T(b) of the
      turtles injected with the high dose. High-dose turtles had significantly higher
      T(b)'s than the control turtles during the first day but not during the second.
      Our results support the prediction of Romanovsky and Szekely that an infectious
      agent may elicit opposite thermoregulatory responses depending on quality and
      quantity of the agent and the host health status.

PMID- 12177831
TI  - Physiological and behavioral variation in estivation among mud turtles
      (Kinosternon spp.).
AB  - Kinosternid mud turtles, a primarily aquatic group, exhibit variable degrees of
      terrestrial activity in the Sonoran and Chihuahuan Deserts. We compared
      behavioral and physiological responses to dry conditions in four populations
      representing three species, Kinosternon sonoriense, Kinosternon flavescens, and
      Kinosternon hirtipes. All four groups were subjected to simulated dry season
      conditions in the laboratory, during which activity was monitored and
      physiological responses (blood chemistry and rates of resting metabolism and
      evaporative water loss) were measured. Kinosternon flavescens and K. hirtipes
      represented extremes in apparent ability to estivate, based on activity and rate
      of increase of plasma osmolality. Two populations of K. sonoriense exhibited
      intraspecific differences in behavioral and physiological measures that were
      related to extant environmental conditions. Large numbers of K. sonoriense from
      Arizona and K. hirtipes, the poorest estivators, had to be rehydrated after only
      30 d out of water. Kinosteron flavescens had the lowest metabolic rates, but no
      evidence of metabolic depression during dehydration was found for any of the four
      populations. We conclude that the differences in capacity for estivation among
      populations are primarily linked to variable behavioral responses to dry
      conditions, though high rates of evaporative water loss in K. hirtipes represent
      a probable physiological constraint.

PMID- 12177832
TI  - Variation in energy metabolism and water flux of free-ranging male lace monitors,
      Varanus varius (Squamata: Varanidae).
AB  - The energy and water used by Varanus varius correlated with changes in weather,
      activity, and possibly the availability of prey. In summer, CO(2) production and
      water influx rates were high (0.147 mL CO(2) g(-1) h(-1) and 23.6 mL H(2)O kg(-1)
      d(-1)) but substantially lower during autumn (0.053 mL CO(2) g(-1) h(-1) and 9.1
      mL H(2)O kg(-1) d( -1)) and winter (0.016 mL CO(2) g(-1) h(-1) and 2.4 mL H(2)O
      kg(-1) d(-1)), increasing again in spring (0.052 mL CO(2) g(-1) h(-1) and 7.9 mL
      H(2)O kg(-1) d(-1)). The summer-winter difference represented more than a
      ninefold reduction in energy expenditure and water flux. However, individual V.
      varius could manipulate their energy and water requirements by up to sixfold
      during the summer period by regulating activity. Although we found no adaptive
      benefits of increased or decreased level of activity, we did find that larger
      animals moved more frequently and over greater distances than smaller animals. We
      hypothesise that V. varius regulates its activity on the basis of the trade-off
      between energy expenditure through activity and energy acquisition through
      foraging.

PMID- 12177833
TI  - Physiological adjustments to arid and mesic environments in larks (Alaudidae).
AB  - Because deserts are characterized by low food availability, high ambient
      temperature extremes, and absence of drinking water, one might expect that birds
      that live in these conditions exhibit a lower basal metabolic rate (BMR), reduced
      total evaporative water loss (TEWL), and greater ability to cope with high air
      temperatures than their mesic counterparts. To minimize confounding effects of
      phylogeny, we compared the physiological performance of four species of larks at
      ambient temperatures (T(a)'s) ranging from 0 degrees to 50 degrees C: hoopoe
      larks (Alaemon alaudipes) and Dunn's larks (Eremalauda dunni) live in hot and dry
      deserts, whereas skylarks (Alauda arvensis) and woodlarks (Lullula arborea) occur
      in temperate mesic areas. Mass-adjusted BMR and TEWL were indistinguishable
      between hoopoe lark and Dunn's lark and between skylark and woodlark. When
      grouping the data of the two desert larks in one set and the data of the two
      mesic larks in another, desert larks are shown to have 43% lower BMR levels and
      27% lower TEWL values than the mesic species. Their body temperatures (T(b)'s)
      were 1.1 degrees C lower, and the minimal dry heat transfer coefficients (h) were
      26% below values for the mesic larks. When T(a) exceeded T(b), the h of hoopoe
      larks and Dunn's larks was high and indistinguishable from h at 40 degrees C, in
      contrast to the prediction that h should be decreased to minimize heat gain
      through conductance, convection, or radiation from the environment when T(a)
      exceeds T(b).

PMID- 12177834
TI  - Digestive response to restricted feeding in migratory yellow-rumped warblers.
AB  - Smaller guts and slow initial mass gains at stopover sites have led to the idea
      that digestive physiology limits refueling rates in migrating birds. We tested
      the digestive-limitation hypothesis in yellow-rumped warblers using food
      restriction to simulate infrequent feeding during migration, which may cause a
      reduction in alimentary tract mass. Restricted birds had small intestine,
      pancreas, and liver masses 18%-22% lower than ad lib.-fed controls. Total
      activities of sucrase, maltase, aminopeptidase, and amylase were significantly
      lower in restricted birds, while those of trypsin and chymotrypsin were not. Only
      aminopeptidase mass-specific activity was significantly lower in restricted
      birds. Previously restricted birds were able to feed and digest at a high rate
      immediately following return to ad lib. feeding. Digestive efficiency did not
      differ between groups. These results suggest that before migration yellow-rumped
      warblers have some spare digestive capacity to compensate for declines in their
      digestive organ masses during migration.

PMID- 12177836
TI  - [On socioeconomic classifications of households: some considerations and a
      proposal].

PMID- 12177835
TI  - [Different sedimentation rates of X- and Y- sperm and the question of arbitrary
      sex determination].

PMID- 12177837
TI  - The demography of the Arab Republic of Egypt:  population issues and policies.

PMID- 12177838
TI  - Population growth in India.

PMID- 12177839
TI  - The demographic transition: an attempt to reformulate a population theory.

PMID- 12177840
TI  - Malthus and neo-Malthusianism in Sweden.

PMID- 12177841
TI  - [Population census in Tanzania].

PMID- 12177842
TI  - Older Workers Benefit Protection Act [16 October 1990]. [Summary].

PMID- 12177843
TI  - Vaccine and Immunization Amendments of 1990 [3 November 1990].

PMID- 12177844
TI  - Omnibus budget reconciliation Act of 1990 [5 November 1990. Excerpts].

PMID- 12177845
TI  - Departments of Labor, Health and Human Services, and Education, and Related
      Agencies Appropriations Act, 1991 [5 November 1990].

PMID- 12177846
TI  - Displaced homemakers self-sufficiency assistance Act [15 November 1990].

PMID- 12177847
TI  - Home health care and Alzheimer's disease amendments of 1990 [15 November 1990].

PMID- 12177848
TI  - Crime Control Act of 1990 [29 November 1990]. [Summary].

PMID- 12177849
TI  - Immigration Act of 1990 [29 November 1990]. [Summary].

PMID- 12177870
TI  - [French policy in the matter of clandestine immigration:  1981-1986].

PMID- 12177871
TI  - [1946-1986:  40 years of immigration policy as seen through the articles in the
      Revue Francaise des Affaires Sociales].

PMID- 12177873
TI  - [Two or three children:  the new decisions that women face].

PMID- 12177872
TI  - [Natality and family models in Council of Europe countries and in France].

PMID- 12177875
TI  - [The odyssey of the Romanian family].

PMID- 12177874
TI  - [Family policies in France and Quebec].

PMID- 12177876
TI  - [Nationalities and demographic characteristics in Yugoslavia].

PMID- 12177878
TI  - [The economics of international migration:  the case of emigration from the
      Maghrib].

PMID- 12177879
TI  - [Is there a European family policy?].

PMID- 12177877
TI  - [Work and fertility in France and West Germany:  do French women perform
      miracles?].

PMID- 12177880
TI  - [Family models, structures, and life cycles].

PMID- 12177881
TI  - [African immigration in France:  from pioneers to family reunion].

PMID- 12177882
TI  - [Population policy in Romania].

PMID- 12177883
TI  - [The socioeconomic consequences of the disappearance of large families].

PMID- 12177884
TI  - [Suicide in Central Europe, France, and Sweden over the past century].

PMID- 12177885
TI  - [Patterns of transfer of funds by immigrant workers].

PMID- 12177887
TI  - [Family allowances, the financial system, and redistribution].

PMID- 12177886
TI  - [Demography and medical consumption].

PMID- 12177888
TI  - [Retirement in peril?].

PMID- 12177889
TI  - [Social security and population.  Demographic change and social policy in France
      since 1945:  from a surge to stagnation].

PMID- 12177891
TI  - Gaining ground on the population front.

PMID- 12177890
TI  - [Family policy and demographic trends:  some perspectives and proposed measures].

PMID- 12177892
TI  - Population programs--how good?

PMID- 12177893
TI  - Africa's population problem.

PMID- 12177894
TI  - Too many children, too close together.

PMID- 12177895
TI  - Family planning program: big strides in 10 years.

PMID- 12177896
TI  - The church.

PMID- 12177897
TI  - The church that pushes family planning.

PMID- 12177898
TI  - Family planning via the postpartum approach.

PMID- 12177899
TI  - Festivals with a purpose.

PMID- 12177900
TI  - Integrating health and family planning services.

PMID- 12177901
TI  - Family planning program: 26% of reproductive-age Filipinos.

PMID- 12177902
TI  - 'Two--no more.'.

PMID- 12177903
TI  - [Studies on male sterilization techniques].

PMID- 12177904
TI  - Studies on vasectomy: VIII. Clinical studies on reversible vas occlusion by
      intravasal thread.

PMID- 12177905
TI  - Studies on vasovasostomy: a cumulative report of the anastomosis of vas deferens.

PMID- 12177906
TI  - Studies on vasovasostomy: surgical techniques and results of vasovasostomy.

PMID- 12177907
TI  - Studies on vasovasostomy: V. Effects of early ambulation on success rate and
      report of 85 vasovasostomies.

PMID- 12177908
TI  - Male sterilization and a modified vasectomy hook.

PMID- 12177909
TI  - Studies on vasectomy.

PMID- 12177910
TI  - Studies on vasectomy: reversible vas occlusion method on experimental animals.

PMID- 12177911
TI  - [Studies on male infertility: 6. Clinical observation on male infertility].

PMID- 12177912
TI  - Japan.

PMID- 12177913
TI  - New Zealand.

PMID- 12177914
TI  - Tanzania.

PMID- 12177915
TI  - Bangladesh.

PMID- 12177916
TI  - Mongolia.

PMID- 12177918
TI  - St. Lucia.

PMID- 12177917
TI  - Paraguay.

PMID- 12177919
TI  - Angola.

PMID- 12177920
TI  - Czechoslovakia.

PMID- 12177921
TI  - Denmark.

PMID- 12177922
TI  - Ecuador.

PMID- 12177923
TI  - Honduras.

PMID- 12177924
TI  - Haiti.

PMID- 12177925
TI  - [South] Korea.

PMID- 12177926
TI  - Italy.

PMID- 12177927
TI  - Venezuela.

PMID- 12177928
TI  - Andorra.

PMID- 12177929
TI  - Guatemala.

PMID- 12177930
TI  - Togo.

PMID- 12177931
TI  - Jamaica.

PMID- 12177933
TI  - Colombia.

PMID- 12177932
TI  - United Kingdom.

PMID- 12177934
TI  - Bolivia.

PMID- 12177935
TI  - Papua New Guinea.

PMID- 12177936
TI  - Albania.

PMID- 12177937
TI  - Dominica.

PMID- 12177938
TI  - Dominican Republic.

PMID- 12177939
TI  - Cape Verde.

PMID- 12177940
TI  - Cambodia.

PMID- 12177941
TI  - European Community.

PMID- 12177942
TI  - Federal Republic of Germany.

PMID- 12177943
TI  - [South] Yemen.

PMID- 12177944
TI  - Luxembourg.

PMID- 12177945
TI  - Pakistan.

PMID- 12177946
TI  - Sweden.

PMID- 12177947
TI  - Tunisia.

PMID- 12177948
TI  - Maldives.

PMID- 12177949
TI  - The Holy See.

PMID- 12177950
TI  - Barbados.

PMID- 12177952
TI  - Mauritania.

PMID- 12177951
TI  - Niger.

PMID- 12177953
TI  - Macau.

PMID- 12177954
TI  - [North] Yemen.

PMID- 12177955
TI  - Qatar.

PMID- 12177956
TI  - El Salvador.

PMID- 12177957
TI  - Iran.

PMID- 12177958
TI  - Belize.

PMID- 12177960
TI  - Poland.

PMID- 12177959
TI  - France.

PMID- 12177962
TI  - Syria.

PMID- 12177961
TI  - Norway.

PMID- 12177963
TI  - Madagascar.

PMID- 12177964
TI  - Nigeria.

PMID- 12177965
TI  - Iraq.

PMID- 12177966
TI  - Lesotho.

PMID- 12177967
TI  - Liberia.

PMID- 12177968
TI  - Kenya.

PMID- 12177969
TI  - Mexico.

PMID- 12177970
TI  - Zimbabwe.

PMID- 12177971
TI  - Djibouti.

PMID- 12177972
TI  - Kuwait.

PMID- 12177973
TI  - Turkey.

PMID- 12177974
TI  - Thailand.

PMID- 12177975
TI  - Taiwan.

PMID- 12177976
TI  - Chile.

PMID- 12177977
TI  - Cameroon.

PMID- 12177978
TI  - Ireland.

PMID- 12177979
TI  - Comoros.

PMID- 12177980
TI  - Burundi.

PMID- 12177981
TI  - Rwanda.

PMID- 12177982
TI  - Malawi.

PMID- 12177983
TI  - Equatorial Guinea.

PMID- 12177984
TI  - Burma.

PMID- 12177985
TI  - Tonga.

PMID- 12177986
TI  - Solomon Islands.

PMID- 12177987
TI  - Sao Tome and Principe.

PMID- 12177988
TI  - Mauritius.

PMID- 12177989
TI  - Gabon.

PMID- 12177990
TI  - Benin.

PMID- 12177991
TI  - Costa Rica.

PMID- 12177992
TI  - India.

PMID- 12177993
TI  - Australia.

PMID- 12177994
TI  - ASEAN.

PMID- 12177995
TI  - Nauru.

PMID- 12177996
TI  - Uruguay.

PMID- 12177997
TI  - Jordan.

PMID- 12177998
TI  - Ethiopia.

PMID- 12177999
TI  - Switzerland.

PMID- 12178000
TI  - Guinea-Bissau.

PMID- 12178001
TI  - Lebanon.

PMID- 12178002
TI  - French Antilles and Guiana.

PMID- 12178003
TI  - Trinidad and Tobago.

PMID- 12178004
TI  - Japan.

PMID- 12178005
TI  - The Holy See.

PMID- 12178006
TI  - Indonesia.

PMID- 12178007
TI  - Yugoslavia.

PMID- 12178009
TI  - Cyprus.

PMID- 12178008
TI  - Egypt.

PMID- 12178010
TI  - Congo.

PMID- 12178011
TI  - Denmark.

PMID- 12178012
TI  - Argentina.

PMID- 12178013
TI  - Hong Kong.

PMID- 12178014
TI  - Philippines.

PMID- 12178015
TI  - Botswana.

PMID- 12178016
TI  - Cote d'Ivoire.

PMID- 12178017
TI  - Saudi Arabia.

PMID- 12178018
TI  - Seychelles.

PMID- 12178019
TI  - Honduras.

PMID- 12178020
TI  - Central African Republic.

PMID- 12178021
TI  - Cape Verde.

PMID- 12178022
TI  - [South] Yemen.

PMID- 12178023
TI  - Sri Lanka.

PMID- 12178024
TI  - Mali.

PMID- 12178025
TI  - Chad.

PMID- 12178026
TI  - Zaire.

PMID- 12178027
TI  - Senegal.

PMID- 12178028
TI  - Malaysia.

PMID- 12178029
TI  - Panama.

PMID- 12178030
TI  - Senegal.

PMID- 12178031
TI  - South Korea.

PMID- 12178032
TI  - Burundi.

PMID- 12178033
TI  - Guatemala.

PMID- 12178034
TI  - Cyprus.

PMID- 12178035
TI  - Panama.

PMID- 12178036
TI  - Honduras.

PMID- 12178037
TI  - Cameroon.

PMID- 12178038
TI  - Chile.

PMID- 12178039
TI  - Pakistan.

PMID- 12178041
TI  - ASEAN.

PMID- 12178040
TI  - Tanzania.

PMID- 12178043
TI  - Costa Rica.

PMID- 12178042
TI  - Chad.

PMID- 12178045
TI  - Norway.

PMID- 12178044
TI  - Qatar.

PMID- 12178046
TI  - Mauritania.

PMID- 12178047
TI  - Comoros.

PMID- 12178049
TI  - Hungary.

PMID- 12178048
TI  - Uruguay.

PMID- 12178050
TI  - Cuba.

PMID- 12178051
TI  - Bangladesh.

PMID- 12178053
TI  - El Salvador.

PMID- 12178052
TI  - Mexico.

PMID- 12178054
TI  - The Gambia.

PMID- 12178055
TI  - Nicaragua.

PMID- 12178056
TI  - Antigua and Barbuda.

PMID- 12178057
TI  - Swaziland.

PMID- 12178058
TI  - Trinidad and Tobago.

PMID- 12178059
TI  - Bulgaria.

PMID- 12178060
TI  - Malta.

PMID- 12178061
TI  - Rwanda.

PMID- 12178062
TI  - Sudan.

PMID- 12178063
TI  - Laos.

PMID- 12178064
TI  - Finland.

PMID- 12178065
TI  - Canada.

PMID- 12178066
TI  - Netherlands.

PMID- 12178067
TI  - Nepal.

PMID- 12178068
TI  - Uganda.

PMID- 12178069
TI  - Algeria.

PMID- 12178070
TI  - St. Kitts and Nevis.

PMID- 12178071
TI  - Papua New Guinea.

PMID- 12178073
TI  - Peru.

PMID- 12178072
TI  - Zambia.

PMID- 12178074
TI  - Ecuador.

PMID- 12178075
TI  - Argentina.

PMID- 12178076
TI  - Vietnam.

PMID- 12178077
TI  - Belgium.

PMID- 12178078
TI  - Liechtenstein.

PMID- 12178079
TI  - Singapore.

PMID- 12178080
TI  - Libya.

PMID- 12178081
TI  - Nicaragua.

PMID- 12178082
TI  - Namibia [South-West Africa].

PMID- 12178084
TI  - Romania.

PMID- 12178085
TI  - Philippines.

PMID- 12178083
TI  - The Gambia.

PMID- 12178086
TI  - Austria.

PMID- 12178087
TI  - Netherlands Antilles.

PMID- 12178089
TI  - China.

PMID- 12178088
TI  - French Antilles and Guiana.

PMID- 12178090
TI  - Maldives.

PMID- 12178091
TI  - Australia.

PMID- 12178092
TI  - Equatorial Guinea.

PMID- 12178093
TI  - Suriname.

PMID- 12178094
TI  - Israel.

PMID- 12178095
TI  - The Bahamas.

PMID- 12178096
TI  - Switzerland.

PMID- 12178097
TI  - Vatican City.

PMID- 12178098
TI  - German Democratic Republic.

PMID- 12178099
TI  - Guyana.

PMID- 12178100
TI  - Portugal.

PMID- 12178101
TI  - San Marino.

PMID- 12178102
TI  - Benin.

PMID- 12178103
TI  - Spain.

PMID- 12178104
TI  - Bahrain.

PMID- 12178105
TI  - Guinea-Bissau.

PMID- 12178106
TI  - Brunei Darussalam.

PMID- 12178107
TI  - Bhutan.

PMID- 12178108
TI  - United Arab Emirates.

PMID- 12178109
TI  - Swaziland.

PMID- 12178110
TI  - India.

PMID- 12178111
TI  - Greece.

PMID- 12178112
TI  - Panama.

PMID- 12178113
TI  - Mozambique.

PMID- 12178114
TI  - Antigua and Barbuda.

PMID- 12178115
TI  - Bermuda.

PMID- 12178116
TI  - Liechtenstein.

PMID- 12178118
TI  - Brazil.

PMID- 12178117
TI  - Monaco.

PMID- 12178119
TI  - Grenada.

PMID- 12178120
TI  - South Africa.

PMID- 12178122
TI  - Hong Kong.

PMID- 12178121
TI  - Cuba.

PMID- 12178123
TI  - Oman.

PMID- 12178124
TI  - Sri Lanka.

PMID- 12178125
TI  - Seychelles.

PMID- 12178126
TI  - Malawi.

PMID- 12178127
TI  - Guinea.

PMID- 12178129
TI  - Fiji.

PMID- 12178128
TI  - Yugoslavia.

PMID- 12178130
TI  - Burundi.

PMID- 12178131
TI  - Western Samoa.

PMID- 12178132
TI  - Central African Republic.

PMID- 12178133
TI  - Somalia.

PMID- 12178134
TI  - Algeria.

PMID- 12178135
TI  - Hungary.

PMID- 12178136
TI  - Costa Rica.

PMID- 12178137
TI  - ASEAN.

PMID- 12178138
TI  - Saudi Arabia.

PMID- 12178139
TI  - Afghanistan.

PMID- 12178140
TI  - Argentina.

PMID- 12178141
TI  - Sierra Leone.

PMID- 12178143
TI  - Burma.

PMID- 12178142
TI  - Morocco.

PMID- 12178145
TI  - [North] Korea.

PMID- 12178144
TI  - Chile.

PMID- 12178146
TI  - Mali.

PMID- 12178147
TI  - Iceland.

PMID- 12178148
TI  - Estimating parametric fertility models with open birth interval data.

PMID- 12178149
TI  - Finnish life tables since 1751.

PMID- 12178150
TI  - Evaluation of U.S. mortality patterns at old ages using the Medicare Enrollment
      Data Base.

PMID- 12178151
TI  - Longevity and month of birth: evidence from Austria and Denmark.

PMID- 12178152
TI  - A search for aggregate-level effects of education on fertility, using data from
      Zimbabwe.
AB  - The analysis was based on the 1994 Zimbabwe Demographic and Health Survey
      combined with aggregate data from the 1992 census. Discrete-time hazard models
      for first and higher-order births were estimated for 1990-94.  The average length
      of education in the district and the proportion who are literate were found to
      have no impact on a woman's birth rate above and beyond that of her own
      education, when it was controlled for urbanization.  This was the case for women
      who themselves had little or no education as well as for the better educated.  So
      far, no significant influence of aggregate education on fertility has been well
      documented in the literature either.  However, in this study, aggregate-level
      effects appeared in models for fertility desires and contraceptive use among
      married women with at least one child.

PMID- 12178153
TI  - The Household Registration System: computer software for the rapid dissemination
      of demographic surveillance systems.
AB  - Although longitudinal experimental community health research is crucial to
      testing hypotheses about the demographic impact of health technologies,
      longitudinal demographic research field stations are rare, owing to the
      complexity and high cost of developing requisite computer software systems.  This
      paper describes the Household Registration System (HRS), a software package that
      has been used for the rapid development of eleven surveillance systems in sub
      Saharan Africa and Asia.  Features of the HRS automate software generation for a
      family surveillance applications, obviating the need for new and complex computer
      software systems for each new longitudinal demographic study.

PMID- 12178154
TI  - Daily fecundability: first results from a new data base.
AB  - This multicenter study has produced a database of 7017 menstrual cycles
      contributed by 881 women.  It provides improved knowledge on length and location
      of the "fertile window" (identified as of up to 12 days duration) and the
      patterns and level of daily conception probability.  The day of ovulation was
      identified in each cycle from records of basal body temperature and mucus
      symptoms.  By referencing days of intercourse to the surrogate ovulation markers,
      estimates of daily fecundability were computed either directly or by the Scwartz
      model, both for single and multiple acts of intercourse in the fertile window. 
      The relationship between coital pattern and fecundability has been explored. 
      Univariate analysis underlines the significant link with fecundability only of
      the woman's reproductive history.

PMID- 12178155
TI  - Empirical assessments of social networks, fertility and family planning programs:
      nonlinearities and their implications.
AB  - Empirical studies of the diffusion of modern methods of family planning have
      increasingly incorporated social interaction within nonlinear models such as
      logits.  But they have not considered the full implications of these nonlinear
      specifications.  This paper considers the implications of using nonlinear models
      in empirical analyses of the impact of family programs, modulated by social
      interaction, on reproductive behavior.  Three implications of nonlinear models,
      in comparison with linear models, are developed. 1) With nonlinear models, there
      may be both low and high contraceptive-use equilibria (i.e., the ultimate level
      of use of modern family planning that a population can be expected to reach after
      the effects of a sustained change in a family planning program have worked
      through the population) rather than just one equilibrium as in linear models.  If
      there are multiple equilibria, then one striking and important result is that a
      transitory large program effort may move a community from sustained low- to high
      level contraceptive use.  2) With nonlinear models, the extent to which a social
      interaction multiplies program efforts depends on whether the community is at a
      low or high level of contraceptive use rather than being independent of the level
      of contraceptive use as in linear models.  3) With nonlinear models, intensified
      social interaction can retard or enhance the diffusion of family planning, in
      contrast to only enhancing diffusion as within linear models.  To clarify these
      implications, for comparison a simple and more transparent linear model is also
      discussed.  Illustrative estimates are presented of simple linear and nonlinear
      models for rural Kenya that demonstrate that some of these effects may be
      considerable.

PMID- 12178156
TI  - Measuring the compression of mortality.
AB  - Compression of mortality is measured here in four ways: 1) by standard deviation
      of the age at death above the mode; 2) by standard deviation of the age at death
      in the highest quartile; 3) by the inter-quartile range; and 4) by the shortest
      age interval in which a given proportion of deaths take place.  The two first
      mentioned are directed at old ages, while the other two measure compression over
      the entire age range.  The fourth alternative is recommended as the most suitable
      for general use and offers several variations, called the C-family of compression
      indicators.  Applied to historical and modern populations, all four measures show
      convincingly that the secular transition from high to low mortality has been
      accompanied by general and massive compression of mortality.  In recent decades,
      however, this development has come close to stagnation even when life expectancy
      continues to increase.  This has happened at a level where compression is still
      so incomplete that the shortest age interval in which 90% of deaths occur, is 35
      years.  It seems unrealistic to expect human mortality ever to be compressed into
      so narrow an age interval that the survival curve would even approximately
      rectangular.  It is considered useful to monitor changes in the compression of
      mortality because the indicators describe relevant aspects of the length of life
      and may acquire new significance as indicators of population heterogeneity.

PMID- 12178157
TI  - Fertility in second unions in Austria: findings from the Austrian FFS.
AB  - The simultaneity of decreasing fertility and changing family structures in many
      European countries has led to a growing interest in fertility behavior in its
      relation to different family structures.  The growing prevalence of higher-order
      unions (and the consequences for parity progression arising therefrom) is one
      example of an ongoing change in fertility behavior.  Childbearing is not
      restricted to a single union but may extend over several partnerships.  Fertility
      behavior in higher-order unions is becoming more and more important for
      determining completed fertility.  Motivated by the work of Vikat et al. 1999, the
      authors investigate fertility behavior in second unions in Austria, focusing on
      whether and how it is influenced by the number of pre-union children of either
      partner.

PMID- 12178158
TI  - Frailty modelling for adult and old age mortality: the application of a modified
      DeMoivre hazard function to sex differentials in mortality.
AB  - Unobserved differences in individual's susceptibility to death are an important
      aspect in the analysis of contemporary mortality patterns.  However, observed
      mortality rates at adult ages, which are usually well described by a Gompertz
      curve, are often perceived inconsistent with frailty models of mortality.  The
      authors therefore propose a modified DeMoivre hazard function that is suitable
      for the application of frailty models to adult and old ages.  The proposed hazard
      increases faster than exponential, and when combined with unobserved frailty it
      can capture a broad range of patterns encountered in the analysis of adult
      mortality.  The authors' application to Bulgaria during 1992-93 suggests that the
      stronger selection process in the male population, caused by an overall higher
      level of mortality, may constitute a primary mechanism leading to the convergence
      of male and female mortality at higher ages.  Hence, the convergence between male
      and female mortality is not necessarily caused by differential process of aging
      across sexes, but is merely a consequence of the different levels of mortality at
      adult ages.

PMID- 12178159
TI  - English historical demography and the nuptiality conundrum: new perspectives.
AB  - "In the last decade, nuptiality has been placed at the centre of the English
      demographic regime in the long eighteenth-century.  Proto-industrial areas in
      particular are increasingly seen to have experienced substantial decline in the
      female age at first marriage during this period, helping to fuel substantial
      population growth. This article uses family reconstitution and other data to
      question the uniformity of this experience and to suggest new avenues of
      interpretation rather than simply observation. For Calverley in West Yorkshire,
      England, female marriage ages remained stable throughout the proto
      industrialisation process. More significantly, the distribution of marriage ages
      around the mean was much narrower than similar measures elsewhere. The article
      suggests that kinship, a deep sentimental and practical attachment to land, and
      an early retirement system lay behind this experience."

PMID- 12178160
TI  - [Religion and demographic behavior: Upper Kassel, 1670-1810].

PMID- 12178161
TI  - Characteristics of European family and household systems.
AB  - "This article establishes that there was considerable diversity in the size and
      composition of the kin group within the household that is not captured by the
      conventional classification of family systems according to the relative
      proportions of simple and complex household forms.  Three case studies are
      presented from England, Corsica and Hungary.  English households fulfilled an
      important welfare role in that they incorporated relatives and non-relatives who
      were not members of core families-- couples or parent(s) and unmarried
      child(ren). The societies of Corsica and Hungary provided a greater proportion of
      their populations with membership of a core family."

PMID- 12178162
TI  - Fertility of populations as a function of the attained level of life expectancy
      in the course of human evolution.
AB  - "?Aging societies' with increasing life expectancies of the average of all their
      members are facts in modern history that are disputed by nobody. What is disputed
      by the most renowned names in demography, however, is that aging populations are
      a consequence of the fall in mortality and thus the increase in life expectancy.
      It is claimed that the [principal] reason for ?aging' is to be found in a drop in
      fertility. In this sense today's demographers regard as a standard result:
      ?Variations in fertility are of more significance for the age structure of
      populations than variations in mortality'. In the following paper this thesis,
      which is based on a neo-Malthusian interpretation of the role of fertility in the
      demographic process, will be questioned."

PMID- 12178163
TI  - [Estimation of infant mortality and life expectancy in the time of the Roman
      Empire: a methodological examination].

PMID- 12178164
TI  - [The retreat of death: the epidemiological transition in Germany during the
      nineteenth and twentieth centuries].

PMID- 12178165
TI  - Different household formation systems in Hungary at the end of the eighteenth
      century: variations on John Hajnal's thesis.
AB  - "John Hajnal's pathbreaking paper about the European marriage patterns and his
      household formation theory provoked high interest [among] researchers even far
      beyond the border of the historical demographic research. Examining them through
      the Hungarian sources we can say that both the declared factors and variables of
      household formation and their regional strength and territorial distribution
      cannot be interpreted unanimously and adequately with the rules established by
      John Hajnal. Maybe it is better not to think in universalistic regimes but,
      moreover, adapt a regional and temporal frame of reference."

PMID- 12178166
TI  - Small town development and urban illiteracy: comparative evidence from
      Leicestershire marriage registers 1754-1890.
AB  - "Based on the analysis of Anglican marriage registers for the period 1754 to
      1890, the article explores patterns of illiteracy in three small Leicestershire
      [England] towns with contrasting economic functions. Illiteracy levels were
      closely related to urban occupational and social structures, which also affected
      distinct gender differentials. Evidence [of] the effect of literacy on age at
      marriage and marriage distance suggests that demographic behaviour and spatial
      interaction were determined more by socio-economic factors than by the possession
      of literacy skills. Literacy attainment, however, was linked to extended marriage
      distances when both spouses could sign the register."

PMID- 12178167
TI  - [Thailand population statistics].

PMID- 12178169
TI  - [Population statistics] as of October 1, 1994.

PMID- 12178168
TI  - [Population statistics] as of July 1, 1994.

PMID- 12178170
TI  - [Population statistics] as of January 1, 1995.

PMID- 12178171
TI  - [Population statistics] as of April 1, 1995.

PMID- 12178173
TI  - [Population statistics] as of January 1, 1994.

PMID- 12178172
TI  - [Population statistics] as of July 1, 1995.

PMID- 12178174
TI  - [Thailand population statistics] as of April 1, 1994.

PMID- 12178175
TI  - [Population statistics] as of Jan 1, 1996.

PMID- 12178176
TI  - [Population statistics] as of July 1, 1996.

PMID- 12178177
TI  - [Population statistics] as of January 1, 1997.

PMID- 12178178
TI  - [Population statistics] as of July 1, 1997.

PMID- 12178180
TI  - [Population statistics] as of July 1, 1999.

PMID- 12178182
TI  - [Population statistics] as of July 1, 1998.

PMID- 12178181
TI  - [Population statistics] as of January 1, 1999.

PMID- 12178183
TI  - [Population statistics] as of January 1, 2000.

PMID- 12178184
TI  - [Population statistics] as of January 1, 1998.

PMID- 12178185
TI  - [Population statistics] as of Oct 1, 1995.

PMID- 12178186
TI  - [Population statistics] as of July 1, 2000.

PMID- 12178187
TI  - [Population education in the Dominican Republic].

PMID- 12178188
TI  - [Adolescent pregnancy prevention].

PMID- 12178189
TI  - [To be a mother at age 15?].

PMID- 12178190
TI  - [Current status of adolescent pregnancy].

PMID- 12178191
TI  - [Men and family planning].

PMID- 12178192
TI  - [No remedy for AIDS?].

PMID- 12178193
TI  - [The wallop of the El Condonazo campaign].

PMID- 12178194
TI  - [Men want to speak out].

PMID- 12178195
TI  - [Contraceptive technology from the administrator's perspective].

PMID- 12178196
TI  - [Adolescent fertility. 1. Pregnancy and childbirth].

PMID- 12178197
TI  - [The history of research on contraceptive methods in the Dominican Republic].

PMID- 12178198
TI  - [Is the adolescent psychologically prepared to have children?].

PMID- 12178199
TI  - [The pharmacist should play an active role in family planning].

PMID- 12178201
TI  - [Follow-up studies of sterilized women].

PMID- 12178200
TI  - [Adolescence and sexuality].

PMID- 12178202
TI  - [CBD: much more than community based distribution of contraceptives].

PMID- 12178203
TI  - [Vietnam and its population].

PMID- 12178204
TI  - [Premature fertility in Sub-Saharan Africa].

PMID- 12178205
TI  - [Cooperation with Vietnam].

PMID- 12178206
TI  - [African populations and AIDS].

PMID- 12178207
TI  - [Cairo: a double deception].

PMID- 12178208
TI  - [The NGO forum in Cairo].

PMID- 12178209
TI  - [Migration and AIDS in Africa].

PMID- 12178210
TI  - [The decline of fertility: the end of the African exception].

PMID- 12178211
TI  - [Crisis and demographic transition in Africa].

PMID- 12178212
TI  - [Sexuality of adolescents in the Sahel].

PMID- 12178213
TI  - [Matrimonial changes in Africa].

PMID- 12178214
TI  - [Political crises in Africa and infant and child mortality].

PMID- 12178215
TI  - [Has the urban transition ended in sub-Saharan Africa?].

PMID- 12178216
TI  - [Population and urbanization in Africa].

PMID- 12178217
TI  - [Demographic policy, family planning and the fertility transition in Africa].

PMID- 12178218
TI  - [Differential mortality by sex in three regions of Ecuador].

PMID- 12178219
TI  - [Maternal mortality].

PMID- 12178220
TI  - [Correction of underregistration of general mortality].

PMID- 12178221
TI  - [Official recognition of a social problem: maternal mortality in Ecuador].

PMID- 12178222
TI  - [Activities of CEPAR].

PMID- 12178223
TI  - [On the health sector crisis].

PMID- 12178224
TI  - [Social participation and health promotion in Cotacachi: an experience in
      progress].

PMID- 12178225
TI  - [Fertility in Loja, Bolivar, Esmeraldas, Azuay and El Oro. Series: Provincial
      reports from the Demographic and Maternal-Child Health Survey, 1994 (ENDEMAIN
      94)].

PMID- 12178226
TI  - [The Assembly and the national priorities ].

PMID- 12178227
TI  - [Public health as a subject for the Assembly].

PMID- 12178229
TI  - [Highland migration toward Quito].

PMID- 12178228
TI  - [Fertility in Imbabura, Los Rios, Carchi, Tungurahua and Manabi. Series:
      Provincial reports from the Demographic and Maternal-Child Health Survey, 1994.
      (ENDEMAIN / 94)].

PMID- 12178230
TI  - [Participative health diagnosis in Cotacachi].

PMID- 12178231
TI  - [Population trends and poverty].

PMID- 12178232
TI  - [Variations in causes of death in Ecuador].

PMID- 12178233
TI  - The impact of population size and the economy on welfare caseloads:  the special
      case of welfare reform.

PMID- 12178234
TI  - Estimating daytime population in the San Diego region.

PMID- 12178235
TI  - An evaluation of population forecast errors for Florida and its counties.
AB  - The authors evaluate the forecasting accuracy of population projections
      formulated at state and county levels for Florida.  They find that "projections
      of Florida population made in the 1970s and 1980s had errors...of approximately 2
      3 percent for 5-year horizons, 5-6 percent for 10-year horizons and 8-9 percent
      for 15-year horizons.  County projections had errors averaging approximately 5,
      10 and 15 percent for these three lengths of horizon, respectively.  Based on
      comparisons with other studies of state and substate population projections, we
      believe this is a good record of forecast accuracy...."

PMID- 12178236
TI  - A comparison of vendor estimates of population and households with 1990 census
      counts in California.
AB  - "This study compares the 1990 [U.S.] population estimates of four national
      demographic data vendors with the actual counts of the 1990 Census. It was
      performed for a consortium of three public utility companies [in California]....
      In addition to total population, this study evaluates the estimates of three
      other demographic variables...:  number of households, population of Spanish
      origin and white population.... Differences in accuracy are found among the
      vendors and between variables.... On average, the estimates were most accurate
      for total population, considerably less so for race (white population) and
      households and by far the least accurate for Hispanic population."

PMID- 12178237
TI  - Estimating Hawaii's de facto population.

PMID- 12178238
TI  - How the 1990 Post Enumeration Survey transformed the census adjustment
      controversy.
AB  - The author briefly examines the controversy surrounding the 1980 U.S. census
      undercount, including a lawsuit entered against the U.S. Bureau of the Census by
      the City of New York. He then describes the Post Enumeration Survey (PES),
      introduced after the 1990 census "to measure census coverage (i.e. undercounts)
      by place and by race and ethnicity, which had not previously been possible....
      Results of the 1990 PES show that previous claims about the harmful effects of
      differential undercounts were exaggerated, but they also [show] that the
      undercounts and their effects are still there."

PMID- 12178239
TI  - Census 2000 planning.

PMID- 12178240
TI  - Using demographic analysis to fix political geography.

PMID- 12178241
TI  - Small area demographic forecasts.
AB  - The author reviews the literature on small area forecasting with a focus on the
      work of Robert Schmitt.  He finds that "the accuracy of small area forecasts has
      not increased appreciably over the past four decades, despite methodological
      progress, increased knowledge gained from the evaluation of forecasts, and more
      widely available and rich data.  A comment made by Schmitt 40 years ago is still
      largely true today, 'No method is yet known for forecasting the population of
      small urban areas with a high degree of accuracy'...."

PMID- 12178242
TI  - Estimating temporary populations.
AB  - The difficulty of tracking temporary short-term population movements (commuting,
      seasonal visitation, convention and business travel) is examined, with a focus on
      Hawaiian statistician Robert Schmitt's work. The author finds that "Schmitt's
      contributions toward a methodology for estimating daytime populations were
      important because this approach utilized data sources that were widely available
      for small areas on at least an annual basis. Consequently, this approach could be
      used for frequent updates of the estimates, for many areas and at relatively
      little cost.... The major drawback of the approach is the lack of solid data on
      temporary residents to serve as larger-area control totals and as a historical
      base for small-area estimates." The geographical focus is on the United States,
      particularly Hawaii.

PMID- 12178243
TI  - Military personnel and dependents in population analysis and projection.
AB  - "Concentrations of [U.S.] armed forces and their dependents create some unusual
      (and little recognized) problems for applied demographers, both in analysis and
      projection.... Their presence complicates both the collection and interpretation
      of data, and has special impact on the preparation of projections."  The authors
      discuss possible ways of resolving these problems.

PMID- 12178244
TI  - The tragedy of the census.
AB  - The author discusses the debate on how to reduce the undercount error in the 2000
      U.S. census. He reviews the history of the census, and considers the impact of
      the "opposing ?interest groups' represented in Congress and elsewhere debating
      methodological issues that can affect the distribution of census-allocated
      resources [who] tend to favor methodological choices that will increase their
      resources."

PMID- 12178245
TI  - Population estimates for small areas in Canada.
AB  - The author outlines population estimation techniques used by Statistics Canada. 
      "The objectives of this paper are to (i) describe the methodology and data
      sources for estimating the population for census divisions (CDs) and census
      metropolitan areas (CMAs), and (ii) present the results of the evaluations of
      1986 population estimates."

PMID- 12178246
TI  - Growth in overcrowded housing:  a comparison of the states.
AB  - "The present article reports on a research project that is seeking greater
      understanding of the prevalence of overcrowding [in the United States] and its
      causes.  First we review the definition of overcrowding and describe differences
      between renters and owners.  Next we document the state-by-state variation in
      crowding levels among renters.  Then we explore some of the factors that may
      explain this variation."

PMID- 12178247
TI  - Sterilization 1.  The changing attitude.

PMID- 12178248
TI  - Effect of child mortality on contraceptive use in rural Iran.

PMID- 12178250
TI  - The absence of fertility questions from the [1981] census and its effects on
      research on fertility patterns.

PMID- 12178249
TI  - Demographic ageing in Denmark in the twentieth century.
AB  - "In the twentieth century the Danish population has, in demographic terms, aged
      considerably, the proportion of the population aged 60 years and over having
      increased from 9.8 to 19.6 per cent.  The expected population development for the
      remainder of this century suggests that this ageing will continue until about
      1990, after which the effects of previous fertility experience will reduce the
      proportions of elderly.  Although the proportion of elderly begins to decrease
      after 1990, the number of persons aged 85+ by the year 2000 is expected to
      increase substantially."

PMID- 12178251
TI  - The demography of prehistoric populations.

PMID- 12178252
TI  - Indicators of archaeological prehistoric demography.

PMID- 12178253
TI  - Infertility in the Chinese population of Hong Kong.

PMID- 12178254
TI  - Marital fertility differentials by women's working status in Korea.

PMID- 12178255
TI  - Medical termination of pregnancy:  a study of acceptor characteristics.

PMID- 12178256
TI  - China's population.

PMID- 12178257
TI  - [Italy in search of an immigration policy].

PMID- 12178258
TI  - [Immigration of seasonal workers in France in 1977].

PMID- 12178259
TI  - [Immigration to Libya].

PMID- 12178260
TI  - [Recent developments in intra-European migration since 1974].

PMID- 12178261
TI  - [Economically active foreign population].

PMID- 12178262
TI  - [Immigration: a problem for a society].

PMID- 12178263
TI  - [Foreigners in Europe in 1977].

PMID- 12178264
TI  - [Permanent return migration of European migrants].

PMID- 12178265
TI  - [Tunisian emigration to Libya].

PMID- 12178266
TI  - [The effects of international migration on the geographical distribution of the
      population].

PMID- 12178267
TI  - [Foreign immigration in the European Economic Community].

PMID- 12178268
TI  - [The brain drain from developing countries to France].

PMID- 12178269
TI  - [Foreign migration in the European Community].

PMID- 12178270
TI  - [British research on migration, immigration, and race relations].

PMID- 12178271
TI  - Economic and social correlates of female employment and fertility.

PMID- 12178272
TI  - Population and labour force growth and patterns in ASEAN countries.
AB  - "The paper shows that the diverse labor dimensions prevailing in the ASEAN region
      can be attributed to changes in the structure of the society and economy in the
      course of recent economic development.  It observes the considerable variety in
      the growth of the population and its effect on the labor force in the ASEAN
      region.... The paper details the similarity and diversity in the level and type
      of labor force participation rates.  A common feature shared by ASEAN countries
      is a general pattern in the age-specific participation rate of men.  In contrast,
      the women, aside from participating in the labor force at a much lower level than
      men at almost all ages, display diverse patterns of participation over the
      working age range.  Lastly, the distribution of the labor force according to
      major industrial sectors in the six ASEAN countries is presented...."

PMID- 12178273
TI  - On the relationship between migration and fertility.

PMID- 12178274
TI  - Asian urbanization and development:  a comparative view.
AB  - A comparative perspective on urbanization trends in Asia is provided.  "The
      trends for the different Asian regions are first presented in the context of the
      world's more developed and less developed regions.  Comparative data on the
      constituent countries in each of the regions are next shown.  Then a modified
      urbanization-development model is proposed and subsequently tested empirically. 
      The concluding section summarizes the findings and implications."  The data are
      taken primarily from published U.N. sources.

PMID- 12178275
TI  - Becker on the interaction between quantity and quality of children.

PMID- 12178276
TI  - Population growth, human capital expenditures and economic growth:  a
      macroeconometric analysis.
AB  - "The paper presents an econometrically estimated model where economic and
      demographic variables are determined simultaneously.  It is used to quantify the
      importance of human capital expenditures in socioeconomic and demographic
      development as well as analyze the effects of rapid population growth on human
      capital expenditures.  The simulation results indicate that human capital
      expenditures are important determinants of economic development, have appreciable
      negative effects on both fertility and infant mortality, hence, have negligible
      net effects on population in human capital expenditures per capita which implies
      a deteriorating quality of human capital."

PMID- 12178277
TI  - Philippine demographic development:  problems and prospects.

PMID- 12178278
TI  - Demographic development in ASEAN:  a comparative overview.

PMID- 12178279
TI  - Age structure and development in ASEAN and Japan:  1950-2015; a preliminary
      report.

PMID- 12178280
TI  - Yellow butterflies and mischief makers: the state of gender policy in Asian media
      today.

PMID- 12178281
TI  - Gender and communication policy in Asia. Special report.

PMID- 12178282
TI  - Feeding frenzy.

PMID- 12178283
TI  - The Lima declaration.

PMID- 12178284
TI  - Lest we forget. A recap on Beijing's Platform J.

PMID- 12178286
TI  - The significance of Lima.

PMID- 12178285
TI  - Cape fearless.

PMID- 12178287
TI  - (Hypo) critical mass: do women make a difference?

PMID- 12178288
TI  - [Toward the realization of the goal of zero population growth].

PMID- 12178289
TI  - [Tables of approximate numbers of population and the area of cultivated land in
      various periods of Chinese history].

PMID- 12178291
TI  - [One couple having one child is the effective way to slow down high fertility in
      China].

PMID- 12178290
TI  - [Study population theories and control population growth].

PMID- 12178293
TI  - [Raising population quality and accelerating the "four modernizations" of our
      country:  a critique of bourgeois population quality theory].

PMID- 12178292
TI  - [The rural population problem in China and its solution].

PMID- 12178294
TI  - [Population problems and theories in old China].

PMID- 12178296
TI  - [Some problems in the history of population development in Sichuan Province].

PMID- 12178295
TI  - [A brief account of population theories, problems, and policies in Chinese
      history].

PMID- 12178298
TI  - [Rural population in Europe and Spain: future perspectives].

PMID- 12178297
TI  - [The Spanish population in the European context].

PMID- 12178299
TI  - [Changes in the active population, occupation, and unemployment in Spain, 1976
      1996].

PMID- 12178301
TI  - [Current mortality in Spain].

PMID- 12178303
TI  - How nations govern growth.

PMID- 12178302
TI  - [The family. Similarity and difference in Spanish family models in the European
      context].

PMID- 12178300
TI  - [Internal structures of childhood mortality (0-4 years) in twentieth-century
      Spain].

PMID- 12178304
TI  - The challenge of population growth.

PMID- 12178306
TI  - Resources, people: uneasy balance.

PMID- 12178305
TI  - Changing ideas of global limits.

PMID- 12178307
TI  - Culture, survival, and family size.

PMID- 12178310
TI  - [Usefulness of census and survey data in the social and health fields].

PMID- 12178309
TI  - [Breast feeding influence on child mortality in the Dominican Republic].

PMID- 12178311
TI  - [Foreign agricultural proletariat and seasonal migrations: Haitian workers in the
      Dominican agriculture].

PMID- 12178308
TI  - [Ideas on socioeconomic and cultural determinants of demographic trends].

PMID- 12178312
TI  - [Territorial mobility: a challenge to social sciences. Summary of the final
      discussion of the workshop, "Territorial Mobility: New Patterns for Latin America
      (the Dominican case)].

PMID- 12178314
TI  - [New findings on labor force and migrations: preliminary data analysis of the
      ENDESA-91 extended household questionnaire].

PMID- 12178313
TI  - [Preliminary internal migration data from the Demographic and Health Survey].

PMID- 12178318
TI  - Special Report: Banjul Islam Conference endorses family planning.

PMID- 12178317
TI  - [Decline of infant and child mortality in the Dominican Republic: an exploratory
      investigation on changes in the structure and composition of socio-demographic
      determinants during the mortality transition].

PMID- 12178316
TI  - [With the things on the back: estate remodelling and inter-urban mobility].

PMID- 12178315
TI  - [Morbidity and mortality and maternal-child health in the Dominican Republic].

PMID- 12178319
TI  - Mozambique to introduce family planning services.

PMID- 12178320
TI  - Incentives in Sri Lanka.

PMID- 12178321
TI  - New Delhi: states must follow sterilization guidelines.

PMID- 12178323
TI  - Ireland (Contraceptive laws).

PMID- 12178322
TI  - Restrictions cancelled in Iraq.
AB  - The Office of the President of Iraq has cancelled Health Ministry regulations
      banning female sterilization and the taking of oral contraceptives without a
      doctor's prescription, according to a report in the Middle East Economic Digest
      of May 23, 1980.

PMID- 12178324
TI  - Condom testing: part 2.

PMID- 12178325
TI  - Planned Parenthood in Bulgaria.

PMID- 12178326
TI  - Marketing fertility regulation.

PMID- 12178327
TI  - One baby in six a foreigner.

PMID- 12178328
TI  - Malthusianism and the IPPF.

PMID- 12178329
TI  - Human relations and sex education in Finland.

PMID- 12178330
TI  - Sex education in Poland.

PMID- 12178331
TI  - Advertising of contraception.

PMID- 12178332
TI  - Oral contraceptive mortality.

PMID- 12178333
TI  - Sex education in Norway.

PMID- 12178334
TI  - The implementation of sex education in Yugoslavia.

PMID- 12178335
TI  - Sex education in France.

PMID- 12178336
TI  - Legal abortion in Europe.

PMID- 12178337
TI  - Legal abortion mortality.

PMID- 12178338
TI  - Contraception in Europe.

PMID- 12178339
TI  - Fertility trends and planned parenthood: (summary report on a subregional working
      group meeting).

PMID- 12178340
TI  - Irish Bill on contraception.

PMID- 12178341
TI  - The CEMP experience in group counselling.

PMID- 12178342
TI  - Sex education training: a Pro Familia pilot project.

PMID- 12178343
TI  - Computerized record system for Irish contraception clinics.

PMID- 12178344
TI  - Postcoital estrogen or IUD?

PMID- 12178345
TI  - Post-coital contraceptive use by adolescents: analysis of contraceptive behaviour
      before and after.

PMID- 12178346
TI  - Sexuality and the handicapped.

PMID- 12178347
TI  - Conference -- summary and comment.

PMID- 12178348
TI  - Updating Malthus' population theory is out of the question today.

PMID- 12178349
TI  - Education for sex and human relationships in Sweden.

PMID- 12178350
TI  - Contraception in the later part of the fertile period in Denmark.

PMID- 12178351
TI  - Counselling in the German Democratic Republic.

PMID- 12178352
TI  - Oh, what a tangled web we weave when first we practise to conceive.

PMID- 12178353
TI  - Feminist initiatives on women's health in the Netherlands.

PMID- 12178354
TI  - Supposing it hurt me too? Abortion: the anguish experienced by men.

PMID- 12178355
TI  - Men Too--a retrospective view of the Family Planning Association's male
      responsibility campaign.

PMID- 12178357
TI  - Fertility regulation in Iceland.

PMID- 12178358
TI  - 1881-1981: a century of organized family planning in the Netherlands.

PMID- 12178356
TI  - The health of women and contraception in Quebec.

PMID- 12178359
TI  - Poland: a step backwards.

PMID- 12178360
TI  - Abortion in Belgium.

PMID- 12178361
TI  - Why no children? Report on a meeting of a Regional Working Group on Psychosocial
      Aspects of Voluntary and Involuntary Childlessness, held in London (UK) on 10-12
      December 1979.

PMID- 12178362
TI  - Women and health: the main questions.

PMID- 12178363
TI  - Feminism and the health movement in Belgium.

PMID- 12178365
TI  - Swedish midwives--a case of professional domination of family planning provision
      by women.

PMID- 12178364
TI  - The feminist position on family planning in Spain.

PMID- 12178366
TI  - Reproductive behaviour in the 1980s: Europe revisited. Council of Europe: an
      account of the work of a committee of experts on fertility trends.

PMID- 12178367
TI  - Planned Parenthood services in teaching hospitals.

PMID- 12178369
TI  - Population aging and social security:  a politico-economic model of state pension
      financing.
AB  - "The present paper attempts to provide a positive, politico-economic explanation
      of actual social security policies [in developed countries].  A theoretical
      framework is devised which integrates individual utility maximization and
      governmental maximization of expected political support.  Individual support
      depends on how net economic benefit from a pay-as-you-go financed state pension
      scheme is translated into a probability of voting for the government.  The
      relation between net economic positions, public policy parameters, and voting
      probabilities is made explicit by referring to the logit model of qualitative
      choice.  The analysis is set in an overlapping generations framework.  Optimal
      state pension policies are characterized, relating such diverse factors as
      population aging, political power distribution, social solidarity, and income
      taxation." (SUMMARY IN FRE AND GER)

PMID- 12178368
TI  - Taxes, divorce-transactions costs, economic conditions, and divorce rates: an
      exploratory empirical inquiry for the United States.
AB  - "This study argues that, given the tax deductibility of alimony payments in the
      United States, higher marginal federal income tax rates may reduce the expected
      transactions costs of divorce and act thereby to increase the divorce rate. After
      allowing for a variety of other factors, including inflation, female labor force
      participation, AIDS, the Vietnam War, age, the availability of legal assistance,
      and transfer payments, both first-differences estimates and Granger-causality
      tests strongly support the hypothesis."

PMID- 12178370
TI  - A survey of the literature on the migration-impact of state and local government
      policies.

PMID- 12178371
TI  - [[Demographic aspects of urbanization in the Lower Yangtze region in China, circa
      1500-1900]].
AB  - Urbanization trends in the Lower Yangtze region of China from 1500 to 1900 are
      examined.  Data are from a variety of sources, including genealogies, local
      records, and other literature.  An attempt is made to analyze the demographic
      characteristics of the urban population.  "The demographic characteristics in
      respect to marriage, fertility and mortality found from the genealogies do reveal
      that there were dissimilarities between the rural and urban dwelling populations.
      Moreover, findings related to migration tend to support that rural to urban
      migration was an important factor that speeded up urbanization in the Lower
      Yangtze Region." (SUMMARY IN ENG)

PMID- 12178372
TI  - Determinants of fertility control in Taiwan: an application of the Easterlin
      framework.

PMID- 12178373
TI  - Threshold hypothesis revisited in the global perspective.

PMID- 12178375
TI  - Quality of life and economic evaluation.
AB  - The author examines "the place and role of quality of life in economic evaluation
      and welfare economics. That exercise certainly involves norms and judgments, but
      it is also influenced by our reading of factual possibilities, and it influences,
      in its turn, the nature of prescriptive possibilities we explore and the
      descriptive statements we choose to make. In this sense, the topic is not
      confined to welfare economics and involves other branches of economics as well."
      This essay consists of two lectures, the second of which examines how longevity,
      life expectancy, and gender- and race-determined mortality differences can
      contribute to our understanding of quality of life.

PMID- 12178376
TI  - Post-war mortality decline and consumption expenditures in Taiwan.

PMID- 12178374
TI  - [A comparative study on fertility transitions in China and Taiwan in historical
      perspective].
AB  - "Mainland China and Taiwan have both successfully undergone remarkable
      transitions from high to low fertility in recent decades. Comparing the
      transitions of the two Chinese populations brings out striking similarities in
      the changes in age patterns of fertility, but distinctive contrasts between the
      trends and speed of declines.... An overview of the history of population
      dynamics in the past 500 years reaffirms the assertion that fertility and
      mortality rates in ancient China were primarily reflections of biological
      responses to population pressure on resources. The results of the regression
      analysis of this study demonstrates that this density-dependent relationship has
      gradually vanished as the deliberate control of fertility prevails in
      contemporary China and Taiwan. The prevalence of fertility control is in large
      part attributable in Taiwan to the rational response of the population to changes
      in economic and social conditions that favor fewer children while the size of
      families in China is largely prescribed by the government there." (SUMMARY IN
      ENG)

PMID- 12178378
TI  - The role of education in fertility transition in Taiwan.

PMID- 12178379
TI  - Possible effects of transportation on mortality differentials in central Taiwan.

PMID- 12178381
TI  - The demographic dynamics of some clans in the Lower Yangtze area, ca. 1400-1900.

PMID- 12178382
TI  - Determinants of income inequality over family development cycle: the case of
      Taiwan.

PMID- 12178380
TI  - Age at marriage and fertility in Taiwan.
AB  - "This study is concerned with the effects of age at marriage on fertility in
      Taiwan, with the primary objective of understanding the nature and causes of the
      recent upsurge of the...birth rate."  Data are taken from the population register
      for the period 1975 to 1978 and from two fertility surveys undertaken in 1967 and
      1976.  It is found that the increase in the birth rate between 1975 and 1978 was
      primarily due to a large increase in the proportion and number of women aged 25
      to 29.  It was also due, in part, to an increase in the age at marriage.  The
      effects of shifts in marriage duration, improved fecundability, and increases in
      premarital pregnancy are also considered.  The author suggests that a further
      decline in fertility is unlikely in the near future unless there are changes in
      traditional family values, son preference, and number of children desired. 
      (summary in CHI)

PMID- 12178377
TI  - Trends in female labor force participation in Taiwan: the transition toward
      higher technology activities.

PMID- 12178383
TI  - Migration and the urban labor market: a case study of Taipei.

PMID- 12178384
TI  - [Trends of phase-specific life expectancy in postwar Taiwan].
AB  - The decline in mortality in Taiwan since World War II is analyzed using life
      tables. "Special features of the research include (1) a phase-of-life-specific,
      rather than an age-specific, analysis of mortality, and (2) the use of measures
      based upon person-years of life in phase intervals, rather than survival rates or
      expectation of life at given ages.  The empirical results suggest that the
      mortality decline can be described as a two-stage process:  an initial stage of
      substantial improvement in life expectancy between 1950 and 1965, and a final
      stage of slow gain in life expectancy since 1965."  Age and sex variations in
      mortality and differing rates of mortality decline are noted.  Implications of
      increased longevity for economic and social programs are also considered. 
      (summary in ENG)

PMID- 12178385
TI  - Agricultural change and population growth:  a brief survey on the case of China
      in historical perspective.
AB  - A historical review of the relationship between agricultural change and
      population growth in China is presented.  "This paper will try to discuss four
      aspects of agricultural change that are related to population growth.  They are: 
      (1) expansion of agricultural frontier, (2) changes in cultivation methods and
      land use, (3) improvements in agricultural technology, and (4) irrigation and
      water-control.  Each of these aspects [is] treated briefly with temporal and
      spatial perspectives...."  The relevance of the Boserup theory that population
      pressure leads to agricultural development is considered in the Chinese context. 
      It is found that some evidence supports the theory.  (summary in CHI)

PMID- 12178386
TI  - Urbanization and economic development policy in Korea.
AB  - "This paper has firstly discussed the development strategy and urbanization in
      [the Republic of] Korea for the period 1960-1980.  [This is] followed with an
      intensive review of the past and recent population redistribution policy of
      Korea.  Finally the authors make some general suggestions which are characterized
      as an expansion of opportunities and services in the underprivileged areas." 
      (summary in CHI)

PMID- 12178387
TI  - [The process of Brazilian urbanization:  a contribution toward the formulation of
      a policy of urban/regional development].

PMID- 12178389
TI  - [The urbanization of Latin America].

PMID- 12178392
TI  - [Urban development and the demographic situation in Chaco and its capital between
      1960 and 1990].
AB  - "The large demographic growth registered in the Chaco province [of Argentina] at
      the beginning of this Century slowed down since the 1950s as a result of the
      successive economic crisis undergone by this province.  The demographic response
      was the outmigration toward the more developed areas of the country and to the
      capital city of Chaco. A large share of Resistencia demographic growth is
      provided by this internal migration.  This rapid increase makes inadequate the
      functional and the service structure of the city." (SUMMARY IN ENG)

PMID- 12178388
TI  - Different roads to a common goal:  the lowering of infant mortality rates in
      Latin America.

PMID- 12178393
TI  - [Rural-urban migration in Tucuman: its impact on the deterioration of the
      environment].

PMID- 12178390
TI  - [Costa Rica:  a geographical approach to the study of its population (1522
      1984)].

PMID- 12178391
TI  - [Population problems in Latin America].

PMID- 12178394
TI  - The Mexico City Metropolitan Area at the beginning of the nineties: demographic
      and socioeconomic indicators in the urban space.

PMID- 12178396
TI  - [The dynamics of the settlement of the semiarid region of Chile].

PMID- 12178395
TI  - [Contemporary demographic survey of Venezuela].

PMID- 12178397
TI  - Population geography of Argentina.

PMID- 12178398
TI  - Estimating interstate internal migration from "place-of-birth" data.

PMID- 12178399
TI  - Migration theory and the Brazilian experience.

PMID- 12178400
TI  - [Potential for migration between a depressed area and alternative destinations: a
      Venezuelan example].

PMID- 12178402
TI  - [Migratory processes and regional planning in Costa Rica].

PMID- 12178401
TI  - [Costa Rica: demographic estimations for the Central Region, 1950-1973].

PMID- 12178403
TI  - [Characteristics of the rural emigration in the Ecuadorian Sierra].

PMID- 12178404
TI  - [Demographic growth and the urban network of the Northeast].

PMID- 12178405
TI  - Migrant flows to La Paz, Bolivia, as related to the internal structure of the
      city:  a methodological treatment.

PMID- 12178406
TI  - [The migration problem in the pan-Amazon region:  a theoretical approximation and
      a methodological alternative].

PMID- 12178407
TI  - [Internal migration in Costa Rica:  a regional approach to the problem].

PMID- 12178408
TI  - Spatial order in the demographic transition:  the Costa Rican case.

PMID- 12178410
TI  - Longitudinal analysis of internal migration to La Paz, Bolivia.
AB  - "This study examines the migration patterns of Bolivians who have moved from
      other provinces to La Paz.  In order to better understand these patterns, the
      capital city was divided into eight similar socio-economic regions and the
      migration patterns analyzed for selected regions.  In addition, the study
      compares the migrant flows for two time periods:  location at the time of birth,
      and the migrant's residence in 1971.  The research analyzes statistically the
      differences between migration fields for a representative area."

PMID- 12178409
TI  - [Population geography and social change in Nicaragua].

PMID- 12178413
TI  - Push factors and pre-1970 migration to southwest Parana, Brazil.

PMID- 12178412
TI  - [A model of socio-spatial differentiation in the metropolitan areas of Latin
      America].

PMID- 12178411
TI  - Censuses of the 1980's and their ground level accountability.

PMID- 12178414
TI  - [Concepts and definitions for a population atlas of Latin America:  a preliminary
      discussion].

PMID- 12178415
TI  - [Study of some demographic processes in Yucatan, 1970-1980].

PMID- 12178416
TI  - [Socioeconomic status and migration retention during the process of frontier
      development in the northern region of Brazil].

PMID- 12178417
TI  - [The main trends in urban and demographic growth in the metropolitan area of San
      Jose from 1950 to 1980].

PMID- 12178419
TI  - The evolution of metropolitan spaces in Brazil.
AB  - "... The purpose of this paper is to show briefly the demographic differences and
      similarities in the evolution of the metropolitan spaces in Brazil, from 1940 to
      1980."  The data are from official sources.  Extensive statistical data are
      included in appendixes.

PMID- 12178418
TI  - Circulation and migration in third world settings:  a comparison in Ecuador.
AB  - This study is concerned with circulation, defined as temporary and repetitive
      migration that lacks any declared intention of a permanent or long-lasting change
      in residence.  "The first section of the paper reviews pertinent circulation
      literature.  Attention then turns to describing circulation and migration
      patterns in Ecuador, and identifying relationships between these patterns and
      regional differentials in economic development, both through cartographic and
      statistical analyses.  A summary and conclusions comprise the last section."

PMID- 12178420
TI  - [Experiences of the urbanization process in Venezuela].

PMID- 12178421
TI  - Latin America:  population, food supply and agricultural dependency.
AB  - The relationships among population growth, food supply, and agricultural
      dependency in Latin America since World War II are examined.  The author notes
      that in the recent past, population growth and agricultural growth have kept pace
      with each other.  However, "most countries appear to be caught in a dilemma
      common to the underdeveloped world:  either increasing emphasis on basic
      foodstuffs to satisfy a growing population and increased per capita demand for
      food or increasing output of export agricultural commodities in order to earn the
      necessary foreign exchange for imports and development."

PMID- 12178423
TI  - [(Multiple correlation between the average number of contraceptive users and
      selected variables describing family planning worker.)].

PMID- 12178422
TI  - An experiment comparing the postabortal performance of the Lippes loop, Copper T,
      and Dalkon shield.

PMID- 12178424
TI  - [Family planning status and dissemination of contraceptive methods in urban slum
      areas].

PMID- 12178425
TI  - General feature of sampling procedure for the World Fertility Survey, Korea,
      1974.

PMID- 12178426
TI  - [Abortion in KOREA: before and after the law].

PMID- 12178427
TI  - [A study of the reliability of survey data on abortion in Korea].

PMID- 12178430
TI  - Measurement of the impact of the National Family Planning Program on fertility in
      Korea: 1960-1975.

PMID- 12178431
TI  - [Impacts of family planning field worker's home visits on acceptance of family
      planning in Korean rural areas (author's transl)].

PMID- 12178429
TI  - A study on the acceptability of male fertility regulating methods in Korea.

PMID- 12178428
TI  - Role of husbands in family planning.

PMID- 12178432
TI  - [Attitudes of women college students in Seoul towards population and family
      planning (author's transl)].

PMID- 12178433
TI  - Family type and fertility: a review of literature.

PMID- 12178434
TI  - Village-based family planning program in Korea: the case of mothers' club.

PMID- 12178435
TI  - The problems in health manpower development: a conceptual analysis.

PMID- 12178439
TI  - A study on some behavioral problems in sequential processes of adoption in family
      planning.

PMID- 12178440
TI  - The central registration system for family planning workers.

PMID- 12178441
TI  - Husband-wife communication and family planning knowledge, attitude and practices
      in Korea.

PMID- 12178438
TI  - Community based distribution programs: description and findings.

PMID- 12178437
TI  - A study on wanted number and sex composition of children of women in a Korean
      rural area, based on Coombs Preference Scale.

PMID- 12178436
TI  - Family planning rumors in Korean rural areas.

PMID- 12178443
TI  - [Recent changes in age-specific abortion rates (author's transl)].

PMID- 12178442
TI  - Relationships between specialization and attitudes toward population related
      issues among professional students in Korea.

PMID- 12178445
TI  - [Analysis of births averted and associated costs under the Korean National Family
      Planning Program; 1962-1979 (author's transl)].

PMID- 12178444
TI  - [System model for resources, environment and population (author's transl)].

PMID- 12178446
TI  - [Consistency of fertility survey data (author's transl)].

PMID- 12178447
TI  - [A study on nurse aid training status in Korea (author's transl)].

PMID- 12178448
TI  - [An analysis for factors affecting parity progression].

PMID- 12178449
TI  - MIgration and fertility in Korea.

PMID- 12178451
TI  - [Economic motives and fertility in Korea].

PMID- 12178453
TI  - Village-based family planning program in Korea: the case of Mothers' Club.

PMID- 12178450
TI  - [Comparative study on the effectiveness of Copper T 200 and Lippes Loop in rural
      community (author's transl)].

PMID- 12178457
TI  - [A study on characteristics of active family planning canvassers (author's
      transl)].

PMID- 12178455
TI  - [An analysis of characteristics of non-program method acceptors (author's
      transl)].

PMID- 12178452
TI  - [The influence of infant mortality on fertility behavior (author's transl)].

PMID- 12178458
TI  - [Evaluation of integrated health workers training of basic course (author's
      transl)].

PMID- 12178454
TI  - [Functional review of drugstores in contraceptive distribution: Cheju area
      (author's transl)].

PMID- 12178456
TI  - [A study on negative information about contraceptive methods (author's transl)].

PMID- 12178460
TI  - [Decomposition of the increasing rate on contraceptive users during 1971-1979
      (author's transl)].

PMID- 12178463
TI  - [An analysis of attitude and behavior on the family size in INFS, 1974 (author's
      transl)].

PMID- 12178464
TI  - [Urbanization and fertility reduction in Korea (Author's transl)].

PMID- 12178462
TI  - [A study on estimating health workers requirement (author's transl)].

PMID- 12178465
TI  - [A study on prospect of sterilization acceptability (author's transl)].

PMID- 12178459
TI  - [Characteristics of government program IUD, sterilization and menstrual
      regulation acceptors in Cheju Province. (author's transl)].

PMID- 12178469
TI  - [Estimation of mortality from census survival rates and consequent estimates of
      birth and death rates].

PMID- 12178461
TI  - [Reference group norm and its effects on fertility behavior].

PMID- 12178466
TI  - [A review on future perspectives of Korean National Family Planning Program based
      on population and family research findings (author's transl)].

PMID- 12178468
TI  - An overview of mortality in Korea.

PMID- 12178471
TI  - [An analysis of the rate of those currently practicing contraception, based on
      the 1976 National Fertility and Family Planning Evaluation Survey].

PMID- 12178472
TI  - [New target setting for the family planning program during the fourth and fifth
      five-year period (1976-1986)].

PMID- 12178473
TI  - [Age of women at marriage and fertility in Korea].

PMID- 12178475
TI  - Some spatial variations in South African mortality.

PMID- 12178478
TI  - A new approach towards environmental management in greater Johannesburg.

PMID- 12178476
TI  - Understanding the nutrition transition.

PMID- 12178481
TI  - Evaluation of community participation in Gazankulu: Elim Care Group System.

PMID- 12178479
TI  - Improving decision making for environmental health in Cape Town -- the HEADLAMP
      field study. Summary of interim findings and future directions.

PMID- 12178480
TI  - The effect of water supply, handling and usage on water quality in relation to
      health indices in a developing community in South Africa.

PMID- 12178484
TI  - WRC Report No. 562/1/96. The effect of water supply, handling and usage on water
      quality in relation to health indices in developing communities.

PMID- 12178483
TI  - Reviewing the health impacts of improvements in water supply.

PMID- 12178467
TI  - [An analysis of fertility for premarital pregnant women (author's transl)].

PMID- 12178482
TI  - XVth World Conference of the International Union for Health Promotion and
      Education, Makuhari, Japan, 20-25 August 1995. Conference report.

PMID- 12178489
TI  - Healthy Marketplaces.

PMID- 12178477
TI  - Community-based distribution of contraception: a pilot project in Khayelitsha,
      Cape Town.

PMID- 12178491
TI  - Towards environment and health promoting South African schools.

PMID- 12178492
TI  - World Health Day 1996. Healthy cities for better life. Message from the Director
      General of the World Health Organisation.

PMID- 12178487
TI  - The Healthy Cities Project in the Islamic Republic of Iran.

PMID- 12178494
TI  - WHO Healthy Cities Programme.

PMID- 12178488
TI  - Coping with urban growth and development through environmental planning and
      management (EPM): the sustainable Dar es Salaam project.

PMID- 12178485
TI  - Habitat II: what is it and is it relevant to Africa?

PMID- 12178499
TI  - Priorities in restructuring for maternal and child health.

PMID- 12178495
TI  - Creating a strong working relationship between the governments and the Community
      for Sustainable Development of Ibadan City, Nigeria.

PMID- 12178503
TI  - Editorial.

PMID- 12178502
TI  - Urbanisation and the epidemic of sexually transmitted diseases in South Africa.

PMID- 12178493
TI  - The Hillbrow Primary Health Care Project.

PMID- 12178490
TI  - The Greater Johannesburg Healthy Foods / Markets Programme.

PMID- 12178497
TI  - Health and development: some concerns about South Africa's health policy.

PMID- 12178486
TI  - World Conference on Local Initiatives for Sustainable Cities, November 2-4 1995,
      Yokohama, Japan. Conference report.

PMID- 12178500
TI  - Preparatory report for workshop on maternity and neonatal services policy for the
      PWV.

PMID- 12178501
TI  - Maximising the benefits of basic service provision through education: the HEAT /
      T initiatives.

PMID- 12178504
TI  - The state of housing, water and sanitation in the greater metropolitan area of
      Cape Town, 1995: report of a survey on access to basic subsistence facilities.

PMID- 12178505
TI  - The Healthy Homes Programme Greater Johannesburg Healthy Cities Project.

PMID- 12178506
TI  - The health effects of exposure through swimming in South African marine waters:
      an overview.

PMID- 12178507
TI  - Evaluation of the short course on Urbanisation and Health for Developing
      Countries presented as part of the Summer School of the Public Health Programme
      at the University of the Western Cape.

PMID- 12178508
TI  - Recent developments in the local environmental health field.

PMID- 12178498
TI  - Rethinking school sanitation and hygiene education curriculum in rural and peri
      urban communities in South Africa.

PMID- 12178496
TI  - Urbanisation of developing populations: what are the health / ill-health
      prospects regarding diseases of prosperity?

PMID- 12178509
TI  - The health of women traders in inner city Johannesburg.

PMID- 12178511
TI  - Report on the Bellagio conference on urban health challenges for the 21st
      century, 9-13 October 1995.

PMID- 12178512
TI  - Water fluoridation.

PMID- 12178515
TI  - Disease and inequalities in infant and child mortality in rural Kenya.

PMID- 12178510
TI  - The practice of travel medicine by family practitioners.

PMID- 12178513
TI  - Environmental planning and management in Greater Johannesburg.

PMID- 12178517
TI  - [Causes of infant-child mortality in Yaounde].

PMID- 12178514
TI  - [The population of Nanga-Eboko: findings of the July 1983 census].

PMID- 12178516
TI  - Diet, malnutrition in sub-Saharan Africa.

PMID- 12178521
TI  - [Urbanization, schooling and infant and child mortality].

PMID- 12178519
TI  - [Seasonality and cause of infant deaths in Yaounde].

PMID- 12178518
TI  - [Kinship systems, a factor in mortality in Africa].

PMID- 12178523
TI  - [Experiences of Cameroon in population planning and economic and social
      development].

PMID- 12178522
TI  - [Population and development in Africa: what future?].

PMID- 12178520
TI  - [Diarrheal morbidity: what therapeutic recourses?].

PMID- 12178524
TI  - [Level of maternal education and mortality: a critical evaluation].

PMID- 12178531
TI  - [An attempt to measure infertility from non-stationary Poisson flows:  an
      application to Cameroon].

PMID- 12178525
TI  - Maternal mortality in sub-Saharan Africa: levels, causes and interventions.

PMID- 12178527
TI  - [Population policies and state intervention: concepts, definitions, objectives,
      domains, and means of intervention].

PMID- 12178530
TI  - [Socioeconomic marginalization:  an endogenous factor in rural out-migration? 
      The case of West and Far-North Cameroon].

PMID- 12178526
TI  - [Infant and child morbidity and mortality due to diarrheal disease in central
      Africa].

PMID- 12178535
TI  - [Some thoughts on the development and implementation of a publication plan for
      results from a population census].

PMID- 12178533
TI  - [The migration and professional characteristics of young people in Medina-Dakar].

PMID- 12178534
TI  - [An analytical approach to migration using data from population censuses in
      francophone Africa south of the Sahara:  the case of Cameroon].

PMID- 12178532
TI  - [The role of internal migration in Burundi's development].

PMID- 12178536
TI  - [Population dynamics, the development of agricultural systems, and agricultural
      production in the densely populated rural areas of Cameroon].

PMID- 12178537
TI  - [Some reflections on the introduction of family planning into businesses in
      Cameroon].

PMID- 12178539
TI  - [Integration of demographic variables in development planning: the case of
      Central African Republic].

PMID- 12178538
TI  - [Nuptiality and fertility in Senegal].

PMID- 12178542
TI  - The population prospect in Monsoon Asia.

PMID- 12178541
TI  - [The school-age population and available school places in Cameroon:  the example
      of primary and kindergarten education].

PMID- 12178543
TI  - Population explosion in Africa: further implications.

PMID- 12178544
TI  - Birth control practices and levels of development in India.

PMID- 12178545
TI  - Population flows in an international context.

PMID- 12178546
TI  - Infant mortality and life expectancy in the Arab world.
AB  - This exercise illustrates the concept of spatial correlation, the categorizing of
      data for mapping, and the use of the scatter diagram.  It employs the variables
      of infant mortality and life expectancy as applied to the Arab World, though any
      region can be used.  The factor of oil exports is added to enhance discussion of
      the findings.  An extra advantage of the exercise is the learning of names of
      countries in a relatively painless way.  The exercise teaches both content and
      methods of interpretation, and it is adaptable to high school and college levels.

PMID- 12178547
TI  - Geography and math: a technique for finding population centers.

PMID- 12178548
TI  - China's urban transition.

PMID- 12178549
TI  - [Time-space analysis of internal migration in Spain (1962-1993): with special
      attention to the changes in migration pattern in the 1970s].

PMID- 12178550
TI  - The changing geography of U.S. Hispanics, 1850-1990.
AB  - "In 1930, the majority of Hispanics were of Mexican descent and lived in the five
      Southwestern states of Arizona, California, Colorado, New Mexico, and Texas.
      After World War II the Latino migrant stream began to diversify and include large
      numbers of Caribbeans, and Central and South Americans who generally settled in
      the Eastern states and California.... The U.S. Hispanic population has increased
      from approximately one million in 1930, to approximately 32 million in 1997. 
      County maps chronicle the changing distribution and numbers of Hispanics from
      1850 to 1990."

PMID- 12178551
TI  - Water resource conflicts in the Middle East.

PMID- 12178552
TI  - The population problem as economic disarticulation.

PMID- 12178553
TI  - International refugees: a geographical perspective.

PMID- 12178555
TI  - Special issue on population.

PMID- 12178554
TI  - California's population geography: lessons for a fourth grade class.

PMID- 12178556
TI  - [New patterns of population change of urban areas in the United States during the
      1970s].

PMID- 12178557
TI  - Population education resources.

PMID- 12178558
TI  - Population trends and the status of population policy in Africa.

PMID- 12178559
TI  - Using US immigration data:  undocumented migration from Mexico to south Texas.

PMID- 12178560
TI  - The migration and distribution of Cubans and Puerto Ricans living in the United
      States.

PMID- 12178562
TI  - [Current observation and analysis of the changes in fertility].

PMID- 12178561
TI  - Facets of the geography of population in the Midwest.
AB  - "This paper explores four selected facets of the geography of population in the
      [U.S.] Midwest that are related to the movement of people:  (1) the spread of
      occupance across the land; (2) the growth of the population of counties once they
      had been occupied; (3) the distribution of the foreign-born population; and (4)
      the distribution of retired people who have migrated after they have retired."

PMID- 12178563
TI  - [Information campaign for the population census, 1987].

PMID- 12178564
TI  - [The number of children of married German women by length of marriage, husband's
      income, and wife's occupational status, 1986].

PMID- 12178565
TI  - [Aliens in federal districts, 1987].

PMID- 12178566
TI  - [Divorces 1986-1987:  principal results].

PMID- 12178567
TI  - [Deaths by causes, 1987].

PMID- 12178568
TI  - [Employment in March 1987:  results of the micro-census].

PMID- 12178569
TI  - [First results of the population census, 1987].

PMID- 12178570
TI  - [Households, 1987--method and results of the population census].

PMID- 12178571
TI  - [Divorces, 1988].

PMID- 12178572
TI  - [Ethnic Germans from East bloc countries and Germans from the German Democratic
      Republic--quantitative development and structure].

PMID- 12178573
TI  - [Forms of living together in 1988].

PMID- 12178574
TI  - [Marriages, births, and deaths, 1988].

PMID- 12178575
TI  - [Employment in April 1988:  results of the microcensus].

PMID- 12178576
TI  - [Population development, 1988].

PMID- 12178577
TI  - [A long-term comparison of 1987 population census results concerning employment].

PMID- 12178578
TI  - [Statistics of the Federal Republic of Germany and the German Democratic Republic
      on the way toward unity].

PMID- 12178579
TI  - [Foreigners, 1989].

PMID- 12178580
TI  - [Singles--an attempt at a definition].

PMID- 12178581
TI  - [Divorces, 1989].

PMID- 12178582
TI  - [Marriages, births, and deaths, 1989].

PMID- 12178583
TI  - [Causes of death in 1989].

PMID- 12178584
TI  - [General life table, 1986-1988].

PMID- 12178585
TI  - [First results of the microcensus, April 1990].

PMID- 12178586
TI  - [Private households yesterday and today:  a look back at the past 150 years].

PMID- 12178587
TI  - [Population trends up to 2030:  results of the seventh coordinated population
      projections].

PMID- 12178588
TI  - [Household and family types in 1972 and 1990:  results of the microcensus].

PMID- 12178589
TI  - [Households and families:  results of the April 1991 microcensus].

PMID- 12178590
TI  - [Marriages, births, and deaths 1990 and 1991].

PMID- 12178591
TI  - [Divorces 1992].

PMID- 12178592
TI  - [Population trends 1992].

PMID- 12178593
TI  - [On voluntary responding to microcensus questions].

PMID- 12178594
TI  - [Nonmarital cohabitation and married couples--forms of partnership yesterday and
      today].

PMID- 12178595
TI  - [First results of the microcensus of April 1993].

PMID- 12178596
TI  - [Analyses of voluntary responses in the microcensus:  are survey results
      distorted by voluntary responses?].

PMID- 12178597
TI  - [Population trends up to 2040].

PMID- 12178598
TI  - [Deaths in 1993 by causes of death].

PMID- 12178599
TI  - [Divorces, 1993].

PMID- 12178600
TI  - [First results of the microcensus, April 1994].

PMID- 12178601
TI  - [Population trends, 1993].

PMID- 12178602
TI  - [Ways of life of the population, 1993].

PMID- 12178603
TI  - [Marriages, births, and deaths, 1993].

PMID- 12178604
TI  - [Trends in private households up to 2015].

PMID- 12178605
TI  - [Divorces, 1994].

PMID- 12178606
TI  - [Marriages, births, and deaths, 1994].

PMID- 12178607
TI  - [Population development, 1995].

PMID- 12178608
TI  - [Divorces, 1995].

PMID- 12178609
TI  - [40 years of the microcensus].

PMID- 12178610
TI  - [Marriages, births and deaths, 1995].

PMID- 12178611
TI  - [The characteristics of private households, 1995].

PMID- 12178612
TI  - [Living situation of households with children: result of the 1993 1% building and
      housing sample].

PMID- 12178613
TI  - [1996 population trends].

PMID- 12178614
TI  - [Marriages, births, and deaths, 1996].

PMID- 12178615
TI  - [First results of the microcensus 1997].

PMID- 12178616
TI  - [Mortality in Germany compared to regional and European trends].

PMID- 12178617
TI  - [Population development, 1997].

PMID- 12178618
TI  - [Divorces, 1997].

PMID- 12178620
TI  - [Labor force participation of married women: results of the microcensus].

PMID- 12178619
TI  - [First results of the microcensus 1998].

PMID- 12178621
TI  - [Reasons for the decline of the birth rate between 1966 and 1975 and number of
      legitimate children required for "zero growth"].

PMID- 12178622
TI  - [Number of children of marriages in the Lander of the Federal Republic: results
      of the microcensus, 1977].

PMID- 12178623
TI  - [Development of the number of German private households, 1961 to 1990].

PMID- 12178624
TI  - [Population development, 1979].

PMID- 12178625
TI  - [Abortions, 1977].

PMID- 12178626
TI  - [Abortions, 1979].

PMID- 12178627
TI  - [Marriages, divorces, births, and deaths of aliens, 1981].

PMID- 12178628
TI  - [Results of the new naturalization statistics, 1981].

PMID- 12178629
TI  - [Aliens in the Federal Republic of Germany, 1984].

PMID- 12178630
TI  - [Population development, 1984].

PMID- 12178631
TI  - [A regional comparison of mortality from selected causes].

PMID- 12178632
TI  - [Marriages, births, and deaths, 1987].

PMID- 12178633
TI  - [Seminar on the significance and possibilities for using the results of
      population and housing censuses].

PMID- 12178634
TI  - [Trends in the number of aliens since 1987].

PMID- 12178635
TI  - [Mortality in regional comparison:  general life tables for the 11 former
      states].

PMID- 12178637
TI  - [Marriages, divorces, births, and deaths of foreigners: long-term comparative
      results for West Germany].

PMID- 12178636
TI  - [First results of the microcensus of April 1991].

PMID- 12178639
TI  - [Marriages, births, and deaths, 1992].

PMID- 12178638
TI  - [Results of the microcensus, May 1992].

PMID- 12178640
TI  - [First results of the microcensus, April 1995].

PMID- 12178641
TI  - [Divorces, 1996].

PMID- 12178642
TI  - [Marriages, divorces, births, and deaths of aliens, 1986].

PMID- 12178644
TI  - [Marriages in April 1977 according to the income of the husband: results of the
      micro-census].

PMID- 12178643
TI  - [Population growth, 1986].

PMID- 12178645
TI  - [Aliens in the Federal Republic of Germany, 1980].

PMID- 12178646
TI  - [Divorces, 1990-1991].

PMID- 12178647
TI  - [Causes of death in a united Germany, 1990-1991:  methodological notes and
      results].

PMID- 12178649
TI  - [Demographic causes of the decline of birth rate].

PMID- 12178648
TI  - [Population trends, 1989].

PMID- 12178651
TI  - [Development of infant mortality and its determinants: results of a special count
      for the year 1973].

PMID- 12178650
TI  - [Abortion, 1978].

PMID- 12178653
TI  - [Catalog of questions and tabulation program of the 1981 population and
      occupation census: state of the preparations at the beginning of 1979].

PMID- 12178652
TI  - [Concept of the 1981 census of population, occupations, and nonagricultural
      units].

PMID- 12178654
TI  - [Households of aliens in the Federal Republic of Germany: results of the micro
      census].

PMID- 12178655
TI  - [Divorces in 1977 according to the old law: transition from the old to the new
      divorce law].

PMID- 12178656
TI  - [Demographic causes of the decline in the birth rate].

PMID- 12178657
TI  - [Marriages, births, and deaths of aliens, 1977].

PMID- 12178658
TI  - [Population development, 1978].

PMID- 12178659
TI  - [Nuptiality tables of widowed and divorced persons, 1972-1974, for the German
      population].

PMID- 12178660
TI  - [Families of aliens in the Federal Republic of Germany, 1978: results of the
      micro-census].

PMID- 12178661
TI  - [Aliens in the Federal Republic of Germany, 1979].

PMID- 12178662
TI  - [Marriages, births, and deaths of aliens, 1978].

PMID- 12178663
TI  - [Deaths by causes in 1977 and 1978].

PMID- 12178664
TI  - [First results of abortion statistics].

PMID- 12178665
TI  - [Abortions, 1978].

PMID- 12178666
TI  - [Ehescheidungen 1979].

PMID- 12178667
TI  - [Marriages, divorces, births, and deaths of aliens, 1979].

PMID- 12178668
TI  - [Population development, 1980].

PMID- 12178669
TI  - [Abortions, 1980].

PMID- 12178671
TI  - [Deaths by causes in 1980].

PMID- 12178670
TI  - [Population development, 1981].

PMID- 12178672
TI  - [Selected data on the development of marriages and births].

PMID- 12178673
TI  - [Divorces in 1980].

PMID- 12178674
TI  - [Aliens in the Federal Republic of Germany, 1981].

PMID- 12178675
TI  - [Marriages, divorces, births, and deaths of aliens, 1980].

PMID- 12178676
TI  - [Divorces in 1981].

PMID- 12178677
TI  - [Aliens in the Federal Republic of Germany, 1982].

PMID- 12178678
TI  - [Population development in the countries of the European Community].

PMID- 12178679
TI  - [Population development, 1982].

PMID- 12178680
TI  - [Abortions, 1981].

PMID- 12178681
TI  - [Abortions, 1982].

PMID- 12178682
TI  - [Development of mortality].

PMID- 12178683
TI  - [Divorces, 1982].

PMID- 12178684
TI  - [Aliens in the Federal Republic of Germany, 1983].

PMID- 12178685
TI  - [Number of children in selected population groups:  results of the 1981 micro
      census].

PMID- 12178686
TI  - [Population development, 1983].

PMID- 12178687
TI  - [Abortions, 1983].

PMID- 12178688
TI  - [Divorces, 1983].

PMID- 12178689
TI  - [The influence of major causes of death on mortality and life expectancy].

PMID- 12178690
TI  - [Abortions, 1984].

PMID- 12178692
TI  - [Nuptiality tables for widowed Germans for 1979-1982 and divorced Germans for
      1980-1983].

PMID- 12178691
TI  - [Marriage tables for single Germans, 1980-1983].

PMID- 12178693
TI  - [Foreigners in the Federal Republic of Germany, 1985].

PMID- 12178694
TI  - [Divorces, 1984].

PMID- 12178695
TI  - [Population predictions:  statistical bases and problems].

PMID- 12178697
TI  - [Census, 1987:  legal bases and general concept according to the ruling of the
      Federal Constitutional Court of December 15, 1983].

PMID- 12178696
TI  - [Population trends, 1985].

PMID- 12178698
TI  - [Divorces, 1985].

PMID- 12178699
TI  - [The purpose and significance of the census of population, employment, and
      housing].

PMID- 12178700
TI  - [An international comparison of censuses].

PMID- 12178701
TI  - [Foreigners in the territory of the Federal Republic of Germany, 1986].

PMID- 12178703
TI  - [The population policy of the USSR].

PMID- 12178702
TI  - [Marriages, divorces, births, and deaths of foreigners, 1985].

PMID- 12178704
TI  - [Statistical materials].

PMID- 12178705
TI  - [Average life expectancy of the population of the USSR].

PMID- 12178706
TI  - [The accuracy of population censuses in the United States].

PMID- 12178707
TI  - [The population of the USSR].

PMID- 12178708
TI  - [On the experience of projecting the family composition of the population of the
      USSR].

PMID- 12178709
TI  - [The socioeconomic structure of the population].

PMID- 12178710
TI  - [Seasonal variation in basic demographic phenomena (the example of Latvian SSR)].

PMID- 12178711
TI  - [Ethnic differentials in fertility in the USSR].

PMID- 12178712
TI  - [Ethnically mixed families in the USSR: structure and dynamics].

PMID- 12178713
TI  - [The organization of automated computation of data from the 1989 all-Union
      population census].

PMID- 12178714
TI  - [Women and children in the USSR].

PMID- 12178715
TI  - [Economic-demographic results of the life of one cohort (based on the cohort born
      in 1950)].

PMID- 12178716
TI  - [All-union population census 1989].

PMID- 12178717
TI  - [All-union population census 1989].

PMID- 12178718
TI  - [Infant mortality].

PMID- 12178719
TI  - [Experiences in evaluating the population figures of the USSR, 1926-1941 (brief
      results of investigations)].

PMID- 12178720
TI  - [From the archives of the State Committee on Statistics: results of the 1937 all
      Union population census. USSR. Gosudarstvennyi Komitet SSSR po Statistike].

PMID- 12178721
TI  - [All-Union population census 1989].

PMID- 12178722
TI  - [Migration as an object of statistical analysis].

PMID- 12178723
TI  - [New information from the State Committee on Statistics of the USSR].

PMID- 12178725
TI  - [The 1989 all-Union population census].

PMID- 12178724
TI  - [Population projections for the USSR].

PMID- 12178726
TI  - [From the history of the 1937 census of population].

PMID- 12178727
TI  - [The 1989 all-Union population census].

PMID- 12178728
TI  - [The 1989 all-Union population census].

PMID- 12178730
TI  - [The 1989 all-Union population census].

PMID- 12178731
TI  - [Demographic problems of military reform in the USSR].

PMID- 12178732
TI  - [The 1989 all-Union population census].

PMID- 12178733
TI  - [The 1989 all-Union population census].

PMID- 12178734
TI  - [Demography and criminality].

PMID- 12178736
TI  - [Population censuses in China].

PMID- 12178735
TI  - [Some unique characteristics of the demographic situation in Russia].

PMID- 12178737
TI  - [Future developments in population statistics].

PMID- 12178738
TI  - [Family size and composition in the USSR].

PMID- 12178739
TI  - [Mortality and life expectancy of the population in the active ages].

PMID- 12178740
TI  - [Family and household].

PMID- 12178741
TI  - [Statistical materials].

PMID- 12178742
TI  - [Population growth among different nationalities in the USSR].

PMID- 12178743
TI  - [The demographic situation in rural areas].

PMID- 12178745
TI  - [Small populations of the north:  their problems and how to solve them].

PMID- 12178744
TI  - [Women in the nation].

PMID- 12178746
TI  - [Territorial-ethnic differentials in fertility and mortality in the USSR].

PMID- 12178747
TI  - [A. V. Chayanov on family size and the peasant household].

PMID- 12178748
TI  - [Socio-demographic interests of the population during the transition to a market
      economy].

PMID- 12178749
TI  - [Demographic analysis and society].

PMID- 12178750
TI  - [Some problems of ethnic migration from Moscow].

PMID- 12178751
TI  - [Preparation of organizational plans for the 1979 population census].

PMID- 12178752
TI  - [Great social achievements: the results of the All-Union population census].

PMID- 12178753
TI  - [All-Union population census:  the structure of households].

PMID- 12178754
TI  - [Statistical materials:  natural increase of population in the USSR].

PMID- 12178755
TI  - [Measurement and analysis of demographic processes:  the characteristics of
      generation].

PMID- 12178757
TI  - [All-Union population census:  family structure].

PMID- 12178756
TI  - [Statistical materials:  the family in the USSR].

PMID- 12178758
TI  - [Toward the All-Union population census of 1989].

PMID- 12178759
TI  - [Births in remarriages (using data from sample surveys)].

PMID- 12178760
TI  - [Women and children in the USSR].

PMID- 12178761
TI  - [On the preparation of organizational plans to conduct the 1989 population
      census].

PMID- 12178762
TI  - [Women in the USSR].

PMID- 12178763
TI  - [An assessment of population losses during World War II].

PMID- 12178764
TI  - [The 1989 all-Union population census].

PMID- 12178765
TI  - [The 1989 all-Union population census].

PMID- 12178766
TI  - [Women in the USSR].

PMID- 12178767
TI  - [Appraisal of the reliability of infant mortality data].

PMID- 12178768
TI  - [1991 Austrian population census].

PMID- 12178769
TI  - [Demographic policy in the light of the resolutions of the Twenty-sixth Congress
      of the Communist Party].

PMID- 12178770
TI  - [Statistical materials.  Part 2:  distribution of families by number of children
      below age 16 by union republic].

PMID- 12178771
TI  - [Explaining to the public the objectives and tasks of the All-Union population
      census].

PMID- 12178773
TI  - [An investigation of shuttle migration of blue and white collar workers in 1978].

PMID- 12178774
TI  - [The experience of committees assisting in the population census].

PMID- 12178772
TI  - [Issues concerning the content and methodology of the upcomming population
      census].

PMID- 12178775
TI  - [Official instructions for the forthcoming All-Union population census of the
      USSR].

PMID- 12178776
TI  - [On the connection between marital status and mortality].

PMID- 12178777
TI  - [Selection and training of cadres are important conditions of a successful
      population census].

PMID- 12178779
TI  - [Migration processes in large cities: a statistical analysis experiment].

PMID- 12178778
TI  - [Toward the All-Union population census].

PMID- 12178780
TI  - [Population by economic occupation].

PMID- 12178781
TI  - [Preparations for processing data from the 1979 All-Union population census].

PMID- 12178782
TI  - [Towards a successful organization of the All-Union population census].

PMID- 12178783
TI  - [Questions of nationality and mother tongue in the 1979 population census].

PMID- 12178784
TI  - [All-Union population census].

PMID- 12178785
TI  - [The family: the most important subject of the population census].

PMID- 12178786
TI  - [Some problems in the organization of processing the results of the forthcoming
      population census].

PMID- 12178787
TI  - [Population reproduction according to the 1926 population census].

PMID- 12178788
TI  - [Methodological and organizational problems of the 1979 All Union Population
      Census].

PMID- 12178789
TI  - [Discussion of the paper by A. A. Isupov, Director of the All Union Population
      Census Division of the Central Statistical Board of the USSR].

PMID- 12178790
TI  - [Current vital statistics].

PMID- 12178791
TI  - [An important phase in the preparation of public information about the census].

PMID- 12178792
TI  - [Population census in the regions of the Far North and areas of difficult
      accessibility].

PMID- 12178793
TI  - [The regions' preparation for the 1979 population census].

PMID- 12178794
TI  - [Natural population growth in the USSR].

PMID- 12178795
TI  - [Data for capitals of Union Republics and cities with a population over one
      million].

PMID- 12178796
TI  - [Women in the USSR].

PMID- 12178797
TI  - [Natural population growth in the USSR].

PMID- 12178798
TI  - [Data for capitals of Union Republics and cities with a population over one
      million].

PMID- 12178799
TI  - [Measurement and analysis of demographic processes: major indicators and
      methods].

PMID- 12178800
TI  - [Censuses as important sources of information on population].

PMID- 12178801
TI  - [The nationality structure of the population of the USSR].

PMID- 12178803
TI  - [Statistical materials:  women in the USSR].

PMID- 12178802
TI  - [All-Union population census:  number of children born].

PMID- 12178804
TI  - [Statistical materials:  natural increase of population in the USSR].

PMID- 12178805
TI  - [All-Union population census:  sources of income].

PMID- 12178806
TI  - [The influence of migration on population growth].

PMID- 12178807
TI  - [All-Union population census:  length of residence of the population by permanent
      place of residence for the whole country and the Union Republics].

PMID- 12178808
TI  - [All-Union population census:  numbers and size of families by autonomous
      republic, krai, and oblast].

PMID- 12178809
TI  - [Statistical materials:  Part 2.  The distribution of families by number of
      children up to age 16 by Union Republic].

PMID- 12178810
TI  - [The aims of population statistics and demographic research].

PMID- 12178811
TI  - [The effect of migration on population development].

PMID- 12178812
TI  - [The dynamics and differentials of fertility in the USSR (survey results)].

PMID- 12178813
TI  - [Statistical materials, Part 1:  natural increase of population in the USSR].

PMID- 12178814
TI  - [All-Union population census].

PMID- 12178815
TI  - [A method of calculating the national composition of the total population between
      censuses].

PMID- 12178816
TI  - [A task of great political importance].

PMID- 12178817
TI  - [A method of computing the marital composition of the population between
      population censuses].

PMID- 12178818
TI  - [Statistical materials. Part 1: statistical data for the capitals of Union
      Republics and cities with more than one million inhabitants].

PMID- 12178819
TI  - [Statistical materials.  Part 4:  natural increase of population in the USSR].

PMID- 12178820
TI  - [World demographic processes and their determining factors].

PMID- 12178821
TI  - [A socio-demographic sample survey of the population in 1985].

PMID- 12178822
TI  - [Statistical materials. Part 3: fertility, mortality, and natural increase].

PMID- 12178823
TI  - [Male nuptiality by real cohorts].

PMID- 12178824
TI  - [Statistical materials.  Part 2:  natural population increase in the USSR].

PMID- 12178825
TI  - [Levels and changes in the length of the economically active life of the
      population].

PMID- 12178826
TI  - [Migration of the rural population under conditions of agro-industrial
      integration].

PMID- 12178827
TI  - [Data from a special survey on young families].

PMID- 12178828
TI  - [Main results of the socio-demographic survey of the population of the USSR
      conducted in 1985].

PMID- 12178829
TI  - [On the 1985 socio-demographic sample survey of the population].

PMID- 12178830
TI  - [The trial population census].

PMID- 12178831
TI  - [Statistical materials].

PMID- 12178832
TI  - [Statistical materials.  Part 3:  life expectancy, infant mortality, and age
      specific death rates].

PMID- 12178833
TI  - Natural family planning: very risky business.

PMID- 12178834
TI  - Observations on new reproductive technologies.

PMID- 12178836
TI  - Abortion in Latin America is a matter of desperation.

PMID- 12178835
TI  - Woman and the fetus: the social construction of conflict.

PMID- 12178837
TI  - New developments in abortion politics.

PMID- 12178838
TI  - Catholic options in the abortion debate.

PMID- 12178839
TI  - Population policy forum. Men, the Church, and pleasure.
AB  - I applaud Marge Berer's initial proposal on feminist population police,
      demonstrating that feminists are capable of construction as well as criticism. 
      Such creative efforts, while partial, are what keep the conversation going and us
      in it.  Several points deserve to be highlighted as they point toward much needed
      changes in public policy.  One is the need to shift the overwhelming burden of
      reproduction from women alone to society in general and men in particular.  This
      is not to give an inch on women;s moral agency and primary decision making.  To
      the contrary, it is to insist that male birth control be an integral part of all
      population policies in action as well as in regulations.  Rates of tubal
      ligations and vasectomies in most countries show that women assume more than a
      fair share, men doing comparative little.  Another important element is the role
      of religion as a shaper of social policy, the Catholic church worldwide being the
      prime example of how sex education, birth control, and abortion are regulated as
      much be theology as by law.  Feminist  s ignore this reality in our peril, though
      dealing head on with it, as some religious professions have found out, is also
      dangerous.  The fact that the majority of women of childbearing age in the US
      ignore the church's pronouncements and use contraception shows that the
      ideological strangle hold is slipping.  We can loosen it further.  A related,
      though perhaps less politically correct, concern in such a feminist proposal is
      the place of sexual pleasure for its own sake.  While public policy is not
      typically concerned with such matters, education is needed for women to feel
      entitled to separate sex from procreation, to enjoy the full range of sexual
      activities for which reproduction is but 1 possible outcome.  This, after all, is
      a major feminist achievement that deserves to made available without delay]

PMID- 12178840
TI  - Population policy forum. Beginning with individual women.
AB  - When IPPF was formed in 1952, its driving force was concern for women, for
      women's health and women's reproductive rights.  40 years on, those same issues
      are still at the heart of IPPF's policies and programs.  Marge Berer has made a
      plea for a feminist approach within international family planning, and IPPF is in
      complete agreement that women's needs and choices should be paramount.  All
      individuals and couples must have the basic human right to decide freely and
      responsible the number and spacing of their children.  Women must also have the
      right to receive full information and counselling to choose their contraceptive
      method.  Our secretary general, Dr. Halfdan Mahler, stresses that if family
      planning is to be effective, it must always begin with the individual, taking the
      whole issue of reproductive health into consideration.  Men must share the
      responsibility for sexual behavior and family planning, and real equality will
      only be attained when women are empowered to regulate their own fertility.  As
      nongovernmental health care organizations, IPPF's member associations offering
      services in 133 countries are able to work towards the principles of informed
      choice and voluntary family planning--even where governments may not be giving
      women the choices they deserve.

PMID- 12178841
TI  - Population policy forum. Women as subjects, not objects.
AB  - I very much agree with Marge Berer that feminists must recognize that there needs
      to be a population policy, worldwide and country by country, that encourages
      lower birth rates and that it is essential to start talking about population
      policies that respect and promote women's moral agency.  Indeed I think it would
      be fair to say that the failure to respect and promote women's moral agency is
      the major reason why government-sponsored population policies have failed in the
      past.  Male population planners habitually think of mass population as objects,
      rather than subjects, of population policy.  This is why they think so readily of
      "incentives" or even more coercive methods.  Birth control is thought of as a
      "war" to be imposed on the population, not as an integral part of the self
      development of the people's own capacity to organize and become decisionmakers. 
      If this is true in relation to the male population, it is even more so in
      relation to women.  Population policy continues the basic male approach to women
      as bodies under their control, not as self-actualizing subjects.  Until
      population policies take as their starting point women's human development as
      persons and moral agents in their own right, such policies both will be abusive
      to women and also will not "work."  However, Marge Berer's remarks about
      oppressive, dehumanizing governments as incapable of promoting any other form of
      population policy give one pause.  If this is the case, then neither national
      governments nor most international agencies linked to Western hegemonic
      neocolonialism can be the authentic promoters of feminist population policy. 
      There must be a global effort to build parallel women's health organizations that
      work on the grassroots level with women, especially poor women, to empower these
      women themselves to become the leaders in educational and economic development of
      the women in their communities.  Only in and through this larger context can such
      women both learn how to use and become empowered to use methods of birth control.

PMID- 12178842
TI  - Population policy forum. Redefining survival.
AB  - Although I agree with most of the content and the essence of Marge Berer's
      excellent paper, I beg to differ with her on whether there is a need for a
      feminist population policy.  If we advocate respect for women's needs and right,
      then we have to believe that women will want to regulate and limit their
      fertility when it is no longer an essential element in their survival:  today,
      childbearing is a social or economic necessity for many women, even to the
      detriment of their health.  No set numbers should be designated as the ideal
      family size, nor should any form of ideal family be posed in the 1st place. 
      However, there is an issue of pragmatism or opportunity value that we have to
      consider.  Women need contraceptives to regulate their fertility, among the many
      other things they need to empower themselves.  Those who control economic
      resources at both the national and international levels are more interested in
      investing in family planning programs than in other health or development needs. 
      We will not be able to change their motives to some abstract egalitarianism in
      which they never believed.  Our challenge, as feminists, is to develop our own
      capabilities in 2 ways.  One is to gain the technical and intellectual know-how
      to make a clearer argument that demonstrates the link between effective
      contraceptive use and addressing women's reproductive health and other economic
      and social needs.  We must convince a reluctant establishment that without
      empowering women they will not achieve their goals.  The 2nd is to create our own
      organizations and modes of operation that will allow resources to flow into
      programs and activities that will work for women and not get marginalized and
      impoverished into paralysis.

PMID- 12178843
TI  - Limited access. Contraceptive costs may impede use.

PMID- 12178844
TI  - If war is "just," so is abortion.

PMID- 12178846
TI  - Arguing with fools.

PMID- 12178845
TI  - The year of dialogue: an update -- slow starts and promising encounters.

PMID- 12178847
TI  - Europe's abortion wars: womb for debate.

PMID- 12178848
TI  - The church's heavy hand in Poland.

PMID- 12178849
TI  - Exporting abortion politics: the battle over international family planning
      assistance.

PMID- 12178850
TI  - Open letter to Pope John Paul II.

PMID- 12178851
TI  - Actions speak louder: a look at congressional votes on human life issues.

PMID- 12178852
TI  - Bishops on birth control: a chronicle of obstruction.

PMID- 12178853
TI  - Historical somersaults.

PMID- 12178854
TI  - On legalizing abortion: an open letter from Mexico's Christian Women's
      Collective.

PMID- 12178855
TI  - Virgin and martyr.

PMID- 12178856
TI  - Abortion in a just society.

PMID- 12178857
TI  - The challenge of prochoice politics.

PMID- 12178859
TI  - The splendor of control.

PMID- 12178858
TI  - Women, sexuality, ecology, and the church.

PMID- 12178860
TI  - Tarnished silver anniversary. Reflections on Humanae Vitae. Galileo all over
      again.

PMID- 12178861
TI  - Sex and justice.

PMID- 12178862
TI  - Natural family planning: point, counterpoint.

PMID- 12178863
TI  - Women and culture. The case for universal rights.

PMID- 12178864
TI  - From Cairo to Beijing and beyond. Women's rights in context.

PMID- 12178865
TI  - Poverty, women, and reproduction. Welfare reform and social justice.

PMID- 12178866
TI  - Responding to religious conservatism. Plenary speech to the Nongovernmental
      Forum, Fourth World Conference on Women, Beijing, 1995.

PMID- 12178867
TI  - To make a seamless garment, use a single piece of cloth.

PMID- 12178868
TI  - Abortion and Catholic thought. The little-known history.

PMID- 12178869
TI  - Investigation of a wrongful death.

PMID- 12178871
TI  - Reflections of a Catholic theologian on visiting an abortion clinic.

PMID- 12178872
TI  - Violent words, violent deeds.

PMID- 12178870
TI  - An open letter from a Catholic birth mother.

PMID- 12178873
TI  - The angry pope.

PMID- 12178874
TI  - The common good. The Canadian bishops and the public debate on contraception.

PMID- 12178875
TI  - Roe v. Wade. Ardently prochoice.

PMID- 12178876
TI  - Roe v. Wade. Revisiting the fundamentals.

PMID- 12178877
TI  - Roe v. Wade: its impact upon the author and his family.

PMID- 12178878
TI  - The international impact of Roe v. Wade.

PMID- 12178880
TI  - Roe v. Wade. On abortion.

PMID- 12178879
TI  - Roe v. Wade, the next twenty-five years.

PMID- 12178881
TI  - Roe v. Wade. Earth's inhabitants.

PMID- 12178882
TI  - How Roe v. Wade has shaped my life and work.

PMID- 12178883
TI  - Roe v. Wade. Jane's perspective.

PMID- 12178884
TI  - Roe v. Wade. Catholic wisdom.

PMID- 12178885
TI  - Roe v. Wade. En la lucha.

PMID- 12178886
TI  - Roe v. Wade. Canada's example.

PMID- 12178887
TI  - Roe v. Wade. Reflective compassion.

PMID- 12178888
TI  - Roe v. Wade. Wayward women.

PMID- 12178889
TI  - Roe v. Wade. Into the next millennium.

PMID- 12178890
TI  - Roe v. Wade. Reality check.

PMID- 12178891
TI  - Roe v. Wade. One step in the right direction.

PMID- 12178892
TI  - Roe v. Wade. The education of one Catholic.

PMID- 12178893
TI  - Catholicism and abortion since Roe v. Wade.

PMID- 12178894
TI  - Emergency contraception and Catholic hospitals.

PMID- 12178895
TI  - A clear message: the Cairo Plus 5 Youth Forum.

PMID- 12178896
TI  - To speak and be heard.

PMID- 12178897
TI  - Catholic Voices and Cairo.

PMID- 12178898
TI  - Barring the way.

PMID- 12178899
TI  - A revolution in the making.

PMID- 12178900
TI  - Words and actions.

PMID- 12178901
TI  - A callous and coercive policy.

PMID- 12178903
TI  - Church or state? The Holy See at the United Nations.

PMID- 12178902
TI  - A calculating alliance.

PMID- 12178905
TI  - Open letter to the Vatican.

PMID- 12178904
TI  - Touching the problem.

PMID- 12178906
TI  - Hard choices.

PMID- 12178907
TI  - Moving forward.

PMID- 12178908
TI  - Ireland's newest import.

PMID- 12178909
TI  - Abortion: taking on the hard questions.

PMID- 12178910
TI  - Ignoring the anguish.

PMID- 12178911
TI  - Religion, women's rights, and the fundamentalist face of Catholicism in Brazil.

PMID- 12178913
TI  - Sex and the body in the Catholic tradition.

PMID- 12178912
TI  - Bribery or benevolence?

PMID- 12178914
TI  - Abortion: a reader's guide.

PMID- 12178915
TI  - Roe v. Wade. Matters sexual.

PMID- 12178916
TI  - Roe v. Wade. My prochoice journey.

PMID- 12178917
TI  - Roe v. Wade. Religious liberty.

PMID- 12178918
TI  - Roe v. Wade. Dismantling patriarchy.

PMID- 12178920
TI  - The New York Times ad.

PMID- 12178921
TI  - Measuring progress: the Cairo Plus 5 Hague Forum.

PMID- 12178919
TI  - Abortion and public policy. A report of the work of the Abortion Task Force of
      the Western Behavioral Sciences Institute.

PMID- 12178922
TI  - Church and state at the United Nations. A case of the emperor's new clothes.

PMID- 12178923
TI  - Beijing + 5: women's rights advocates stand firm against backsliding on Platform
      for Action.

PMID- 12178924
TI  - Paper justice.

PMID- 12178925
TI  - Religion, reproductive health and access to services. A national survey of women.

PMID- 12178926
TI  - Abortion: articulating a moral view.

PMID- 12178927
TI  - Dissenting view. A Brief, Liberal, Catholic Defense of Abortion [by] Daniel A.
      Dombrowski and Robert Deltete. Book review.

PMID- 12178928
TI  - The Vatican at the United Nations. Cairo + 5.

PMID- 12178929
TI  - Abortion: a guide to making ethical choices.

PMID- 12178930
TI  - Reproductive rights:  an international sample.

PMID- 12178931
TI  - Catholic attitudes toward abortion.

PMID- 12178932
TI  - Religious freedom and family life:  reflections on the right to choose.

PMID- 12178934
TI  - Catholics and abortion: authority vs. dissent.

PMID- 12178933
TI  - Biblical views on abortion:  an Episcopal perspective.

PMID- 12178935
TI  - Ethical dilemmas in population policy.

PMID- 12178936
TI  - The refugee situation in Thailand.

PMID- 12178937
TI  - The Canadian approach to the settlement and adaptation of immigrants.

PMID- 12178938
TI  - United States refugee and asylum policy: history and current approaches.

PMID- 12178939
TI  - Assessment of the MAA Incentive Grant Initiative.

PMID- 12178941
TI  - Europe: crossroad in the search for asylum.

PMID- 12178940
TI  - Country reports on five key asylum countries in eastern and southern Africa.

PMID- 12178942
TI  - The plight of the refugee: a case in point--Africa.

PMID- 12178943
TI  - A history of U.S. legislation with respect to immigration from India.

PMID- 12178945
TI  - Foreign workers in Germany: the Turkish connection.

PMID- 12178944
TI  - International migration:  new challenges to Europe.
AB  - This report, which was commissioned by the Secretary General of the Council of
      Europe, is an overview of the situation concerning current and future trends in
      international migration in Europe.  The most important components of the current
      scene are identified as "(i) persisting unemployment despite the economic
      recovery in Europe, (ii) the continued internationalisation of the national
      societies in conjunction with overt tendencies to xenophobia, (iii) the
      strengthening of European political and economic integration, and (iv) the
      increasing pressure for immigration from the third world."

PMID- 12178946
TI  - Migration seen from Germany.

PMID- 12178947
TI  - Residency patterns and secondary migration of refugees.
AB  - "This paper synthesizes available research regarding the residency patterns of
      refugees in the United States."  Consideration is given to the impact of policy
      on residency patterns and to the effect of secondary migration on the geographic
      distribution of refugees.  "The first section of the paper presents an historical
      background to this issue, tracing the evolution of U.S. policy and outcomes from
      1945 to the start of the Indochinese resettlement program in 1975.  The second
      part focusses upon the residency patterns of the 1975 Indochinese arrivals, and
      the third section deals with refugees who have arrived since 1979."

PMID- 12178948
TI  - The United States Refugee Act of 1980.

PMID- 12178950
TI  - The migrant family in six European countries.

PMID- 12178949
TI  - Children of migrant workers in Sweden--adjustment and behaviour at school.

PMID- 12178951
TI  - The migrant family: socio-political problems and responsibilities.

PMID- 12178952
TI  - The Cuban refugee crisis of 1980: challenge and response.

PMID- 12178954
TI  - Patterns of migration among Christian minorities in the Middle East.

PMID- 12178953
TI  - Refugee resettlement and development principles: towards a refugee integration
      policy in New Zealand.

PMID- 12178956
TI  - The Australian resettlement approach.

PMID- 12178955
TI  - The Haitian boat people: political or economic refugees?

PMID- 12178957
TI  - Venezuela's indocumentados.

PMID- 12178958
TI  - Undocumented migrants and the regularization of their status: the United States
      experience.

PMID- 12178959
TI  - Immigration reform: what is it and when will it come to the United States?

PMID- 12178960
TI  - Refugee aid and development: report from the meeting of experts.

PMID- 12178961
TI  - Considerations in the design of employment-generating activities for refugees.

PMID- 12178962
TI  - Refugees in the developing world: a challenge to the international community.

PMID- 12178964
TI  - U.S. refugee admissions: processing in Europe.

PMID- 12178963
TI  - Voyagers in the land: a report on unaccompanied Southeast Asian refugee children.

PMID- 12178965
TI  - Incorporating an analysis of gender to the study of migration:  the case of
      Peruvian migration patterns.

PMID- 12178966
TI  - Of special humanitarian concern: U.S. refugee admissions since passage of the
      Refugee Act.

PMID- 12178967
TI  - Birth control in the third world.

PMID- 12178968
TI  - Land, energy and water: the constraints governing ideal U.S. population size.

PMID- 12178970
TI  - How to get there from here: the demographic route to optimal population size.

PMID- 12178969
TI  - The second great wall of China: evolution of a successful policy of population
      control.

PMID- 12178971
TI  - How to influence fertility: the experience so far.

PMID- 12178973
TI  - Population and the "EIS".

PMID- 12178972
TI  - Neighbors' problems, our problems: population growth in Central America.

PMID- 12178974
TI  - Oil, Egypt and Israel: the view in 1995.

PMID- 12178975
TI  - The most overpopulated nation.

PMID- 12178976
TI  - Balancing humans in the biosphere: escaping the overpopulation trap.

PMID- 12178977
TI  - The biologist and the economist: is dialogue possible?

PMID- 12178978
TI  - Europe in the energy transition: the case for a smaller population.

PMID- 12178979
TI  - Energy and population: transitional issues and eventual limits.

PMID- 12178980
TI  - The timid crusade.

PMID- 12178981
TI  - The Cairo conference: feminists vs. the Pope.

PMID- 12178982
TI  - Sobering news from the real world. Clinton on population, Part 1.

PMID- 12178983
TI  - The two child family.

PMID- 12178984
TI  - Confronting the 21st century's hidden crisis: reducing human numbers by 80%.

PMID- 12178985
TI  - Social security: the Ponzi path to dystopia.

PMID- 12178986
TI  - The tightening conflict: population, energy use, and the ecology of agriculture.

PMID- 12178987
TI  - Preparatory committee's final session set to negotiate programme of action.

PMID- 12178989
TI  - Women, population and development.

PMID- 12178988
TI  - Anti-discrimination committee takes up ICPD issues.

PMID- 12178990
TI  - Third PrepCom consolidates broader approach to population, development.

PMID- 12178991
TI  - Dr. Sadik's remarks at PrepCom press conference.

PMID- 12178993
TI  - World Population Day to focus on ICPD themes.
AB  - The eighth annual World Population Day will be celebrated world-wide on 11 July
      1994.  Last year, activities marking the occasion took place in more than 110
      countries.  According to Dr. Nafis Sadik, Executive Director of the United
      Nations Population Fund (UNFPA) and Secretary-General of ICPD, this year's
      celebration will help draw attention to the upcoming Cairo Conference and to its
      themes of "choices and responsibilities"--the basic right and responsibility of
      couples and individuals to make informed choices about child-bearing, and the
      responsibility of societies to help them in achieving their reproductive goals. 
      To promote World Population Day, UNFPA's Information and External Relations
      Division has produced a colorful poster, a 15-minute video (available in English,
      French and Spanish) emphasizing maternal health, and a special pamphlet and a new
      edition of the Population Issues Briefing Kit (both in English, French, Spanish
      and Arabic).  The kit outlines the major issues to be addressed at ICPD.  UNFPA
      is also sponsoring a 5-15 July exhibit at UN headquarters, featuring photos and
      text from Material World: A Global Family Portrait, a book to be published in
      October.  The book, by Peter Menzel, will document an extraordinary project in
      which 16 prominent photographers travelled to 30 countries to photograph typical
      families surrounded by all their possessions--in some cases a few jars and jugs,
      in others an abundance of electronic gadgetry.

PMID- 12178992
TI  - Study projects demographic impact of AIDS in Africa.

PMID- 12178994
TI  - The road to Cairo: creating a new approach to population, development.

PMID- 12178995
TI  - Donors promise increased support for population, reproductive health.

PMID- 12178996
TI  - Informal talks held on ICPD draft programme.

PMID- 12178997
TI  - Hungary hosts consultative meeting on ICPD.

PMID- 12178998
TI  - Parliamentarians' meeting to precede ICPD.

PMID- 12178999
TI  - Cairo conference maps out "path to a better reality".

PMID- 12179000
TI  - Dr. Sadik: ICPD was a "quantum leap".

PMID- 12179001
TI  - Final touches put on conference arrangements, documentation.

PMID- 12179002
TI  - News in brief: [Anglican Archbishop Desmond Tutu voices strong support for family
      planning].
AB  - On June 16, the Day of the African Child, Anglican Archbishop Desmond Tutu of
      South Africa voiced his strong support for family planning.  At a Cape Town news
      conference, the church leader said, "Planned parenthood is an obligation of those
      who are Christians. Our church thinks we should use scientific methods that
      assist in planning of families... It is far better to have children that we want
      than to say you must have children, no matter what."  In regard to ICPD, the
      archbishop said, "The call that is being put out for this UN conference...is not
      just a Western thing.  There are very many in other parts of the world who
      believe the issues raised there are crucial issues."  The UN Children's Fund
      sponsors the annual Day of the African Child to call attention to the problems
      facing African children.  The date was chosen in memory of the children of
      Soweto, South Africa, who were massacred on 16 June 1976, when Africans tried to
      speak out against the brutality of apartheid.

PMID- 12179003
TI  - President Mubarak, Turkish Family Planning Foundation receive UN population
      award.

PMID- 12179004
TI  - IMF / World Bank boards of governors discuss population, migration.

PMID- 12179005
TI  - Cairo work schedule, procedures outlined in letter to governments.

PMID- 12179007
TI  - State Department leader describes new U.S. commitment to women's rights.

PMID- 12179006
TI  - Pre-conference review of ICPD draft Programme of Action begins.

PMID- 12179008
TI  - Quantitative goals in the ICPD draft Programme of Action.

PMID- 12179009
TI  - Determinants and characteristics of female migration: a case study of Salem City
      in Tamil Nadu, India.
AB  - A random sample of 521 male and 481 female migrants surveyed in Salem city in
      Tamil Nadu, India, during 1980-1981 was analyzed on the basis of a classification
      related to reasons (association, marriage, distress, and voluntary) for
      migration.  Women were found to outnumber males in associational migration, both
      in rural to urban and urban to urban streams.  They also formed almost all the
      marriage migrants.  They were more numerous in distress migration as well.  There
      were, however, comparatively few women among voluntary migrants.  The incidence
      of illiteracy among migrant women was generally high, except for voluntary
      migrants who had completed high school.  The share of working women was not
      negligible, but in most cases present work status was achieved after migrating.

PMID- 12179010
TI  - Demographic transition in small countries.
AB  - Half of the world's 200 countries have less than 3.37 million inhabitants, and
      many of these small countries are often assumed to experience rapid demographic
      transition.  This is true of many of the small island populations of the
      developing world, especially those with largely immigrant and pluralistic
      populations, unusual family structures, and rapid economic development. 
      Smallness of population alone, however, is not sufficient to ensure rapid
      demographic transition and many small countries of mainland Africa have
      experienced little transition.

PMID- 12179011
TI  - A geographical approach to some demographic features of the Moslem countries.
AB  - This paper considers some demographic aspects of the world's Moslem population. 
      Main sources of information are evaluated, and a definition is laid down for a
      Moslem country.  Proportions of Moslem population are given for some 20 Asiatic
      and 30 African countries.  Geographical distribution of Moslem countries as well
      as of the total world population are studied in some detail with due attention
      being devoted to Moslem minorities in non-Moslem countries such as China and the
      USSR.  Population density, annual growth rate, life expectancy, age and language
      distributions are among the demographic features discussed comparatively at
      country and continent levels.  Special attention is given to urbanization in the
      Moslem world.  Finally future trends are discussed by using the usual statistical
      methods.  It is thus established that by the year 2000 the proportion of world's
      Moslem population will rise to 22.4% as compared with 18.3% in 1975 and that the
      pressure on natural resources of the Moslem countries will be more than twice
      that in 1975 which is an alarming fact.  It is hoped that the study will assist
      Moslem leaders in adopting sound population policies in their respectivie
      countries.

PMID- 12179012
TI  - Some economic implications of population dispersion in Canada.
AB  - In New Brunswick, as in the rest of Atlantic Canada, the quality of life is
      highly prized, and for many inhabitants this means a rural life style.  New
      Brunswick (with the exception of Prince Edward Island) is the most rural of the
      Canadian provinces.  In addition, over time it is becoming more rural.  This
      paper examines some of the economic implications arising from the rural life
      style.  The provincial government also has expressed concern over rural
      dispersion in New Brunswick, hence this paper is predominantly policy-oriented. 
      It argues that social costs are considerable, and advocates increased emphasis on
      user-pay pricing.  The intention is not to prohibit rural non-farm residence, but
      merely to charge rural dwellers a portion of the social costs they impose.  The
      political feasibility of such a policy is open to question, but the alternatives
      may be increased tax rates or a reduced level of service, and these may be even
      more politically unpopular.

PMID- 12179013
TI  - Recent population growth in India.

PMID- 12179014
TI  - Some factors influencing variations in the rate of natural increase of population
      in western Maharashtra.
AB  - This paper analyzes the impact of various factors on variations in the rate of
      natural increase of population in Western Maharashtra, India.  By using district
      level data, coefficients of correlation have been calculated between the rate of
      natural increase, the birth rate and the death rate on the 1 hand and different
      factors affecting them on the other.  The analysis shows that in Western
      Maharashtra the birth rate is high in response to the high death rate and the
      high infant mortality rate.  It is also revealed that the rate of natural
      increase of the population declines with an increase in the proportion of working
      females as well as the proportion of educated males.  All this signifies that the
      region under study is in the 2nd stage of the "demographic transition."

PMID- 12179015
TI  - Spatial patterns of out-migration in Maharashtra: 1961-71.
AB  - In view of the importance of migration in Maharashtra state.  India an attempt is
      made to identify the areas of out-migration, and to assess the probable causes
      for it.  The analysis is confined to the decade 1961-1971 and based on secondary
      data, with the taluka as the unit of analysis.  The total number of births and
      deaths in each taluka for the period of study was complied and enabled the
      natural increase of population to be computed.  A comparison of this with the
      actual increase as indicated by the census made it possible to identify the areas
      of out-migration.  The study revealed that the out-migration talukas were located
      in 3 areas and that the relative significance of out-migration varied.  The
      analysis indicated that the causes of out-migration were probably unfavorable
      relief efforts, susceptibility to drought, closure of household industries, and
      the 'pull' effect of metropolitan centers like Bombay.

PMID- 12179016
TI  - Female migration to Taipei: process and adaptation.
AB  - Women form an increasing proportion of migrants and of the non-agricultural labor
      force in Taiwan.  However, many questions regarding female migration in Taiwan
      have remained unanswered since the focus of the migration literature in the past
      has been on male migration.  This paper examines the decision process of rural
      urban migration and adaptation of rural female migrants to the Taipei metropolis.
      The analysis is based on interviews of 96 female migrants who have moved to
      Taipei from villages.  The reasons for migration are severalfold.  With rapid
      expansion of employment in the manufacturing and urban service sectors, women are
      attracted to urban occupations, most of which require unskilled labor.  Migrants
      are also motivated by psycho-social reasons.  The "glamour" and "convenience" of
      city and greater chances for further education through work-study programs are
      all perceived by migrants to provide alternatives to hard and unrewarding farm
      lives.  Though the initiative and final decision to move come from the migrants
      themselves, most only do so, however, with the consent and advice of their
      parents.  The choice of moving to Taipei, rather than some other city, is mainly
      influenced by friends or relatives who are alrady there.  Their initial jobs and
      accommodations are arranged by friends and relatives.  The majority of women are
      employed in unskilled or semi-skilled occupations.  Even though they change jobs
      frequently in order to find better employment terms and pay, they experience
      limited upward mobility.  Homesickness, unfamiliarity with the city environment,
      limited resoureces, and social lives are major problems for the rural female. 
      Freequent home vistits are made in between jobs to relieve themselves of
      homesickness and the pressures of city life.  Once settled, they do not segreate
      themselves by village origin in their occupation or palces of residence in the
      city, but they have a tendency to interact socially with other migrants of rural
      origin rather than city people.

PMID- 12179017
TI  - Spatial mobility and reasons for migration of Japanese women.
AB  - This paper discloses, istly, the spatial mobility of Japanese women and its
      change mainly between 1970 and 1980, through comparison with the men's mobility,
      in respect of distance of movement, age patterns, and labor force status, using
      population census data.  Secondly, the chief reasons for the migration of women
      by types of migratory flows are examined using the data derived from the survey
      on reasons for migration conducted in 1981 by the Land Agency of the Government
      of Japan.  Results show that the spatial mobility of Japanese women is smaller
      than that of men in long distance movements but is almost the same in short
      distance moves, and that the age pattern of spatial mobility of the women is
      nearly the same between both distances of movement.  Also, it is disclosed that
      the mobility of women not in the labor force is higher for the whole country but
      lower in metropolitan areas than that for men.  The prime reason for the
      migration of women is employment, the as same as that for men for the whole
      nation, but this varies between the types of migratory flows.

PMID- 12179018
TI  - Impacts of river bank erosion on population displacement in the lower Brahmaputra
      (Jamuna) floodplain.
AB  - "This study has attempted to focus on dimensions and impacts of displacement by
      river bank erosion in the lower Brahmaputra (Jamuna) floodplain of Bangladesh. 
      Based on a survey of 547 randomly selected households, it was observed that about
      two thirds of the floodplain inhabitants were displaced at least once in their
      life time."  The socioeconomic consequences are discussed, and implications for
      development planning are considered.

PMID- 12179019
TI  - A spatial perspective on the distribution of the Indians in the United Kingdom,
      1981.

PMID- 12179020
TI  - Poverty, development and patterns of rural male outmigration in Uttar Pradesh.

PMID- 12179022
TI  - Density of rural population in an Indian situation: a contemporary approach.

PMID- 12179021
TI  - Religious composition of Punjab's urban population, 1981.

PMID- 12179023
TI  - Changing population concentration in India: a macro-regional scenario.

PMID- 12179024
TI  - Is India overurbanised?
AB  - This paper questions the frequently posed thesis of India being overurbanized. 
      The diverse connotations of the term "overurbanization" have been taken into
      account and tested against the Indian reality.  It is concluded that on a net
      balance of positive and negative effects emanating from urbanization, there is no
      reason to believe that India is urbanized to an extravagant degree.  Any
      continued adherence to the "overurbanization" thesis is likely to distort our
      perceptions about the vital role which Indian urbanization is playing in economic
      growth.

PMID- 12179025
TI  - Christianity in India:  a temporal-spatial view.
AB  - The author "attempts to analyse the spatial diffusion of Christianity in India
      from the earliest times to the present."  Consideration is given to the history
      of Christianity, its diffusion throughout the country, the response of different
      social groups to Christianity, and the impact of British colonial rule on the
      growth of the religion.  It is concluded that the "distribution of Christians in
      the country is highly uneven and is associated with the vast historic, socio
      economic and political diversity of various parts of the country."  Data are from
      official and other published sources.

PMID- 12179027
TI  - Outmigration patterns in development transition of rural areas.

PMID- 12179026
TI  - Political economy of population growth.
AB  - Tracing the origin of political economy as a class-science, this paper focuses on
      the political economy of population growth.  Exposing the limitations of
      Malthusian ideas and their invalidity even for the capitalist economies, it
      discusses the subsequent revival of the Malthusian model during the period of de
      colonization and the misinterpretation of the relationship between population
      growth and development in the developing and developed countries.  Taking India,
      China, and Japan as some case studies, the paper examines the relationship
      between birth rate levels and some correlates.  It elaborates on the Indian
      experience, emphasizing the association of population growth with poverty and
      unemployment and lays bare some of the hidden causes of these phenomena.  The
      authors examine some interstate variations in India and identify constraints and
      prospects of the existing population policy.  The paper proposes outlines of a
      democratic population policy as an integral part of India's development strategy
      which should recognize human beings not simply as consumers but also as producers
      of material values.  It pleads for 1) restructuring of property relations; 2)
      bringing down the mortality rates and raising of the literacy levels, especially
      among females; and 3) improving nutritional levels, as prerequisites for bringing
      down birth rates.

PMID- 12179028
TI  - Indians in England: why did they emigrate?

PMID- 12179029
TI  - Education as a determinant of fertility: a case study of Kullu Town.

PMID- 12179030
TI  - Overcrowding:  a behavioral perspective.

PMID- 12179032
TI  - Distributional pattern of the major agricultural communities (Ahirs, Gujars, Jats
      and Rajputs) in their traditional abode of the northwestern Indian subcontinent.

PMID- 12179031
TI  - Growth of rural population in Punjab, 1971-81.

PMID- 12179033
TI  - Religion and fertility:  a study in differentials.

PMID- 12179034
TI  - Continuity and change in population movement:  the case of Nepal.

PMID- 12179035
TI  - Regional diversity in some aspects of Indian demography.

PMID- 12179036
TI  - Demographic characteristics of the environs of Tarapur atomic power station.

PMID- 12179038
TI  - Spatial mobility in India:  evolving patterns, emerging issues and implications.
AB  - "This study examines the patterns of spatial mobility in India as expressed at
      the inter-state level for the post-Independence period. Comparing these patterns
      with those which had been evolving throughout the colonial period the paper
      probes into the processes of dislocation of people in the context of India's
      development strategy.... The analysis points out the complex interrelationships
      with the nature of socio-economic development and suggests alternatives for
      stemming distress migration from the backward regions."

PMID- 12179037
TI  - Population policy and the Five Year Plans.

PMID- 12179039
TI  - Demographic development in an Indian state:  a case study of Rajasthan.
AB  - "The paper attempts to analyse the patterns of and trends in demographic
      development in Rajasthan state [India] by employing the indices of urbanization,
      literacy and occupational diversification.... An effort has also been made to
      define the concept of demographic development...."  Demographic development is
      defined as improvement in the quality of the population in a given area.

PMID- 12179040
TI  - Regional disparities in demographic development in India.
AB  - "The main objective of the present paper is to discern the changing pattern of
      regional disparities in demographic development in India. The analysis pertains
      to the 1971-81 decade using district level data. Indicators have been selected
      from the demographic components of urbanisation, literacy and occupational
      dynamism."

PMID- 12179041
TI  - Contributions of the IGU and ICA commissions in population studies.

PMID- 12179042
TI  - Growth of India's scheduled caste population, 1971-81:  a spatial analysis.
AB  - The author analyzes the spatial distribution and the rapid growth rate of India's
      scheduled caste population since 1971 and finds that "there are wide regional
      disparities in their rates of population growth.  Areas with relatively high
      growth rates are associated with (i) accelerated process of urbanisation and
      industrialisation, (ii) expansion in mining activity, and (iii) intensification
      and commercialisation of agricultural development based on irrigation.  By
      contrast, areas experiencing low rates of growth are associated with (i)
      continuing high mortality rate, and (ii) net out-migration arising from scarcity
      of resources, acute poverty and subjection to deprivations...."

PMID- 12179043
TI  - Population and geography in India.

PMID- 12179044
TI  - Migration patterns in India.
AB  - "The chief objective of the present paper is to comprehend the broad spatial
      patterns of internal migrations in India."  Aspects considered include data
      constraints, the magnitude of internal migration, interstate migration, migration
      to rural and to urban destinations, spatial patterns, and areas of origin and
      destination.

PMID- 12179045
TI  - Growth of rural population:  a case study of Patiala district, Punjab.
AB  - "Based on the census data, the present paper focuses on patterns of rural
      population growth in the Patiala district [India] during 1951-81. The striking
      spatial variations in growth rate were associated largely with migration
      differentials in the study area.  Similarly, there were wide differentials in the
      population growth rates between scheduled castes and non-scheduled castes and
      among different religious communities. The proportion of different castes and
      communities to the total population changed due to their uneven growth rates."

PMID- 12179046
TI  - Literacy differentials in tribal and non-tribal population of India, 1981.
AB  - The author investigates literacy differentials between tribal and non-tribal
      populations in India, using 1981 census data. "Spatially, the index is high in
      tradition gripped and economically backward areas of Western Rajasthan, of
      central highlands and of Western Arunachal Pradesh.  It is low in [the] Christian
      tribal belt of [the] northeast; the early exposed areas of [the] southern
      peninsula, parts of Gujarat, Maharashtra and Karnataka, and numerically
      insignificant areas of northern Rajasthan and Western Himalayas."

PMID- 12179047
TI  - Ethnic structure of Calcutta:  a study of minority communities.
AB  - "The main objective of this study is to understand the distribution, socio
      economic status, behaviour and life-style of some minority communities of
      Calcutta.... This study will concentrate only on three overseas minority
      communities, i.e. Chinese Jews and Parsees and one community with mixed origin
      e.g., Anglo-Indian."

PMID- 12179048
TI  - Work force of India's scheduled caste population: a spatial perspective.

PMID- 12179049
TI  - Regional variations in the female age at marriage in India:  an analysis by agro
      climatic zones.
AB  - "The effect of agro-climatic factors on female age at marriage [in India] is
      studied by carrying out areal analysis of the 1981 Census data. The study found a
      close association between agricultural and climatic conditions in an area and
      corresponding female age at marriage.  In general, women in Himalayan regions and
      coastal areas have higher age at marriage than most hinterland regions. 
      Rainfall, altitude, forest area, land availability and productivity are observed
      to be associated with female age at marriage. In addition, female age at marriage
      in rural areas is found to be more sensitive to the agro-climatic conditions.  It
      is hypothesized that with socio-economic and technological development, the
      agricultural and climatic factors are losing their grip on female age at marriage
      in India."

PMID- 12179050
TI  - Demographic processes of urbanisation in Delhi.
AB  - "Metropolitanisation has been observed by experts as one of the main
      characteristics of Indian urbanisation.  Rural to urban migration has been a
      major player in urban growth of metropolitan cities, particularly Delhi.  Not
      only Delhi but its hinterland [are] urbanising fast as compared to the
      hinterlands of other major cities of India.  There are several processes of
      urbanization viz. historical, physical, demographic and economic.  In this paper
      the role of demographic processes in urban expansion of Delhi [is examined]."

PMID- 12179051
TI  - Spatial pattern of migration of plantation labour and its dynamics.
AB  - "This study examines the issue of migration trends being witnessed by areas of
      plantation agriculture [in India].  The focus is on the linkages between
      structural changes in local economies, the overall development policy and
      people's responses to plantation agriculture both as an economic activity and as
      a way of life. Based on field data, it is a case study of Hassan district,
      Karnataka."

PMID- 12179052
TI  - Income distribution in rural Sagar.
AB  - "The study makes an attempt to identify the pattern of household income
      distribution in rural areas, based on the socio-economic surveys in Sagar
      district [in India]."  Factors affecting family income include "occupational
      structure, distance from nearby urban centers and general accessibility.... The
      rural settlements under urban influence or with proper accessibility have a
      greater percentage of high-income families.  The major source of income for over
      a third of the rural families of the district is agricultural labour, while
      another third earns its living by other agricultural work and the rest are either
      petty businessmen or are engaged in services."

PMID- 12179053
TI  - Population and development linkages: perspectives and research tasks.

PMID- 12179054
TI  - Processes and factors of metropolitanization in India.

PMID- 12179055
TI  - The linguistic pattern of Hungarian population.
AB  - "This study focuses on some aspects of the linguistic geography of Hungary....
      Hungary today is a small country having a relatively homogeneous ethnic
      composition. However, it shows several interesting peculiarities when examined in
      terms of its linguistic pattern. The main goal of the study is to reveal these
      peculiarities and to find explanations for the great territorial differences
      therein. Along with a universal use of Hungarian as the first language, an east
      west, a core-periphery and a north-south dichotomy is observed in respect of the
      second language knowledge."

PMID- 12179056
TI  - Settlement network development policy and urbanisation in Hungary in the 20th
      century.
AB  - "The paper brings out the role of political economy in influencing the process of
      urbanisation and [the] structure of settlement network. This is demonstrated
      through an empirical study of Hungary during the twentieth century. Three phases
      get easily distinguished: pre-1949 or the period of changes in the state
      boundaries; 1949-89 or the period of state socialism; and post-1989 or the period
      of institutional reform.  An interesting finding is that there was a bias in
      favour of large cities and county seats in allocation of development funds under
      all the regimes."

PMID- 12179057
TI  - A typology of migration in Canada based on migrants' characteristics.
AB  - "Data from the 1981 Census of Canada are used to develop a typology of migrants
      on the basis of their personal characteristics. Migrants are defined as those
      individuals who have changed their residence since the 1976 Census, crossing at
      least a municipal boundary. Socio-economic and demographic characteristics are
      perceived to differentiate stayers from movers, and to distinguish each migrant
      type [that is to say] intraprovincial, interprovincial and international.
      Discriminant analysis is applied to classify people into migrant types based on
      their personal characteristics and the typology developed."

PMID- 12179059
TI  - Fertility differentials in Madhya Pradesh, India.
AB  - "The present paper explains the fertility differentials among socio-cultural
      groups and regions in the central Indian state of Madhya Pradesh and examines the
      role of such factors as general and female literacy, age at marriage and infant
      mortality in determining the fertility levels. The study indicates that no single
      factor is of overwhelming importance. These factors in combination, as revealed
      by multivariate analysis, account for about 29 percent inter-district variation
      in fertility in the state."

PMID- 12179058
TI  - Female infanticide and child neglect as possible reasons for low sex ratio in the
      Punjab, 1881-1931.
AB  - "The social and cultural practices prevalent in various parts of [India] resulted
      in the neglect of the female child...[in general, and] probably more so in the
      Punjab. Moreover, female mortality significantly exceeded male mortality in years
      of epidemics and famines. This paper tries to examine the socio-cultural and
      economic factors, namely, the system of land holdings and inheritance strategies,
      structured customs in different parts of the province, and notions of honour and
      status which probably have been at the back of neglect of the girl child. Among
      certain caste groups even female infanticide might not have been uncommon."

PMID- 12179060
TI  - Age patterns of fertility in Madhya Pradesh.
AB  - "The purpose of this paper is to analyse age-patterns of fertility in Madhya
      Pradesh [in India] based on district level estimates of aggregate measures of
      fertility data collected in 1981.... Four clusters of districts have emerged
      which reveal a clear zonal pattern in age-specific fertility rates in the state.
      These groups bring out high fertility rates in the north and north-western parts
      of the state, gradually declining toward the south-eastern zone. The author
      suggests that separate policies and programmes be evolved for each of the
      clusters of districts for the purpose of bringing about reduction in fertility
      and promoting family welfare in the state of Madhya Pradesh."

PMID- 12179061
TI  - Population growth in Uttar Pradesh since 1872.
AB  - "The present paper aims to analyse district-wise decadal growth of population in
      Uttar Pradesh [India] since 1872. It also attempts to identify population growth
      regions based on a suitable statistical technique. The spatio-temporal
      differentials are explained by the three interacting processes of birth, death
      and migration."

PMID- 12179062
TI  - Urbanisation in Himachal Pradesh during the present century.
AB  - "The paper examines urbanisation in Himachal Pradesh [India] in terms of size,
      growth, evolution, site and functional characteristics of urban centres for [the]
      1901-91 period. In addition, the role played by the changing political and
      administrative geography has also been considered."

PMID- 12179063
TI  - Tibetan immigrants in India.
AB  - "This paper documents the current evidence of the state of the Tibetan society in
      India with special reference to the trends in social transformation, livelihood
      patterns and cultural adaptation to a geographically alien environment....Three
      and-a-half decades of living in India [have] demonstrated how a culture group can
      survive by carving out ecological niches in ethnically segregated social space
      and yet adapt to a new cultural environment without losing its identity."

PMID- 12179065
TI  - A demographic profile of the Marathwada earthquake victims.
AB  - "[The] Marathwada earthquake, one of the worst natural calamities in India so
      far, happened to be a factor in the loss of thousands of human and animal lives
      and the destruction of a vast stretch of natural environment. In this study an
      attempt has been made to enlist the quake affected victims and to analyse their
      demographic characteristics in terms of their distribution at district level."

PMID- 12179064
TI  - Geography and migration policies: the Indian experience.

PMID- 12179066
TI  - Map Series: 3. Infant mortality in India.

PMID- 12179067
TI  - Development and population growth: the Indian experience.

PMID- 12179068
TI  - Population distribution problems and policies in Asia.
AB  - "The main purposes of this paper are (1) to identify the primary population
      distribution problems in Asia, and (2) to identify the range of explicit
      population policy instruments or packages designed to alleviate or solve existing
      maldistribution.  As a corollary to these main goals, attempts are made to
      classify types of spatial population problems and policies and to compare them
      across nations.  Additionally, a qualitative analysis is made to assess the
      effectiveness of population distribution policies in those cases where there are
      reasonable data available."

PMID- 12179069
TI  - Internal migration and development transitions in South East Asia.

PMID- 12179070
TI  - Redistribution of population in India: some reflections.

PMID- 12179071
TI  - Migration of scheduled caste population in rural Bist Doab (Punjab).

PMID- 12179072
TI  - Slow growing towns in India.

PMID- 12179073
TI  - Literacy in India's scheduled caste population:  a spatial analysis.

PMID- 12179074
TI  - Socio-demographic area of Delhi.
AB  - "This paper evaluates statistically and displays cartographically previously
      untabulated and unpublished data from the 1971 Census of India for the entire
      population of Delhi.  Data pertain to Delhi's census 'charges' (wards) and were
      originally tabulated in the form of 348 variables relating to occupational
      distribution, migration, and non-worker status--each classified separately by
      gender.  Although these data are subject to multiple reporting errors and
      fallacious ecological inferences, they constitute the largest database yet
      assembled for comparative analysis of Indian intra-metropolitan patterns and
      structures.  Socio-demographic patterns and areas are identified reflecting the
      traditional-modern, formal-informal, familistic, and ethnic constituents of the
      national capital of India."

PMID- 12179075
TI  - Male-female literacy differential in India--1981.
AB  - The author examines inequalities in the literacy rates between males and females
      in India.  Regional variations in literacy are examined by district using maps. 
      "The male-female literacy differential is low in coastal, peripheral and
      metropolitan areas and is high in inland and mountainous areas.  These regional
      disparities are the product of differences in length of educational background,
      age at marriage, level of urbanisation, standard of living and proportion of
      socially conservative and backward sections of society.... The study in spatial
      dimension provides a strong base for the removal of sex biased discrimination in
      society."

PMID- 12179076
TI  - Differential urban growth as a process of redistribution of population:  a case
      study of Sao Paulo state, Brazil.
AB  - "This paper identifies the process of the differential concentration of
      population in urban areas....[Data for the state of Sao Paulo, Brazil, have] been
      subjected to an ambiguous model of development. This model is reflected in the
      pattern of population distribution."

PMID- 12179077
TI  - Regional dimensions of population in India.
AB  - "The present endeavour has an emphasis on analysing distributional patterns of
      some...population characteristics [in India] as a case perceived at the
      physiographic-regional level, that is to say, the variability of population
      characteristics over different natural environments as well as within a similar
      physical entity.  Specifically it aims at analysing the pattern of population
      density, growth, urbanisation level and literacy varying from one physiographic
      region to [another] and the relationship of these four variables with each other
      at the same level of regional structure."

PMID- 12179078
TI  - Urban development policy in India with special reference to Himachal Pradesh.

PMID- 12179079
TI  - Dynamics of educational development in the Chhattisgarh region, India.
AB  - "The aim of this paper is to analyse the spatial patterns of the level of
      educational development along with the decennial change in the literacy rate in
      the Chhattisgarh region of Madhya Pradesh State [India]. Eleven variables...have
      been considered to find out the index of educational development in the tahsils
      [divisions] of the region.  The eighty two tahsils...are grouped into four
      categories...on the basis of decennial growth rate in literacy during 1981-91 and
      the level of educational development...."

PMID- 12179081
TI  - Migration as a phenomenon and process of population change.

PMID- 12179080
TI  - Female literacy in Rajasthan, 1961-1981.
AB  - "The paper attempts to highlight the significance of female literacy in Rajasthan
      [India] as an instrument of socio-economic change, [especially] among its
      scheduled tribe and scheduled caste components."

PMID- 12179082
TI  - Changes in the industrial structure of India's male working force, 1961-81.
AB  - The post-Independence period in India has witnessed a gradual decline of some
      occupations and services and the emergence of others.  In the present paper an
      attempt has been made to analyze the change in the industrial structure of
      India's male working force by calculating an index of change.  The index so
      calculated for 2 decades separately (1961-1971 and 1971-1981) is portrayed
      cartographically.  The overall low degree of change recorded by the country's
      male working force establishes the weakness of India's industrial infrastructure.
      Consequently, the secondary sector seems to have failed in generating employment
      opportunities on a large scale.  Regionally, the peripheral areas have recorded a
      higher incidence of change than the interior heartland of the country.  The areas
      that were overwhelmingly agricultural and had experienced developments in the
      field of agriculture alone exhibited a low degree of change in comparison to
      those that had experienced developments both in the field of agriculture and
      industry.  During the last inter-censal period (1971-1981) the country recorded
      an accelerated rate of change in the industrial structure of its male working
      force.  Spatially too, the increasing rate of change has spread to new regions.

PMID- 12179083
TI  - National capital region of India:  a case of metropolitan growth management.

PMID- 12179085
TI  - Population concentration:  a consideration of density measures and correlates.
AB  - "The purpose of the paper is to explore the nature of association of certain
      external and internal density measures with each other and with a set of selected
      variables in four states of India.  Pearson's Simple Coefficient of Correlations
      and Stepwise Multiple Regression were used for analysis of data.  The results
      reinforce the notion of a clear distinction between external and internal density
      measures and their associative factors in India; the two measures of internal
      density, although highly correlated, were found to have varied relevance to the
      dependent variables."

PMID- 12179084
TI  - A case for internal migration policy in India.

PMID- 12179086
TI  - Governments' perceptions and policies of population redistribution in East and
      South East Asia.
AB  - "This paper is based on the results of the Third Inquiry among Governments on
      Population and Development carried out in 1977 by the UN Secretariat.  It reports
      on perceptions and policies concerning international migrations, spatial
      distribution of the national population, internal migration and settlement
      patterns in fourteen South East and East Asian countries.  "It appears that
      nearly all countries under consideration were concerned with the spatial
      distribution of population both as a factor related to problems caused by
      excessive natural increase and as a problem on its own right.  The majority of
      countries were prepared to pursue policies affecting basic trends in internal
      migration.  Most governments declared their willingness to alter patterns of
      rural or both rural and urban settlement.  Only two countries were interested in
      increasing emigration; the remaining ones were satisfied with the existing levels
      of international migration."

PMID- 12179087
TI  - Conflicts between explicit and implicit population distribution policies in Asian
      development plans.

PMID- 12179088
TI  - Decision makers in migration--Papua New Guinea.

PMID- 12179089
TI  - Remittances and migration--the commerce of movement.
AB  - "This paper comments upon the role of remittances in a variety of emigrant
      situations, traces the way remittance patterns change over time and evaluates the
      importance of remittance payments for personal and national economies.  It
      considers the concept of 'remittance-societies" in the South Pacific and
      elsewhere, and briefly examines the various mechanisms involved in the emigration
      remittance cycle, including the expectation of interactions and interdependence
      that exists between migrants and their home-based kin, and the sacrifices and
      hardships often endured by many migrants to meet obligations back home."

PMID- 12179090
TI  - Rural-urban redistribution of population in West Asia.

PMID- 12179092
TI  - IGU special issue on population redistribution in Asia and the Pacific region.

PMID- 12179091
TI  - A perspective on population growth in India.

PMID- 12179093
TI  - The determinants and consequences of female migration in Thailand.
AB  - Female migration in Thailand, especially from rural areas to the Bangkok
      Metropolis, is an important migratory phenomenon which leads to an unfavorable
      population distribution.  Generally the migration level in Thailand is low but
      many women from the rural areas, especially from the Northeast Region, move to
      Bangkok Metropolis to seek work.  Findings reveal that the majority of migrants
      are young, single women.  Women migrants find it relatively easy to participate
      in the Bangkok labor market.  Service work is the main source of employment.  For
      the temporary migrants, it was found that those from the Northeast Region tend to
      return to their hometown in higher proportion than those from other regions. 
      This was particularly so among young women migrants.

PMID- 12179094
TI  - Demographic transition in Sri Lanka: a spatial perspective.

PMID- 12179095
TI  - Dynamics of population growth: Bundelkhand region--a case study.

PMID- 12179096
TI  - Population size, distribution and growth in Iran.
AB  - The author examines population size, distribution, and growth in Iran using data
      for 1966, 1976 census data, and some historical data for the nineteenth century. 
      "This paper discusses changes in the size of population through time, population
      distribution, and regional patterns of population growth of the 23 provinces.  It
      has been argued in this paper that because of a large family size norm as a
      religious duty to increase the numbers of the Islamic faith, early age at
      marriage, especially among females, common practice of polygamy, and the war with
      Iraq, population will grow even faster.  It is concluded that population policy
      must be integrated into the national development plans."

PMID- 12179097
TI  - The development process and urbanisation in a newly organised state:  a case
      study of Haryana.
AB  - "This paper examines the impact of emergence of Haryana [India] as a new state in
      1966 on its development and concomitant urbanisation process.  The analysis is
      based on data for individual towns for all the post-Independence censuses of 1951
      to 1981.  It was found that urban growth in the state was far more rapid during
      the post-1966 period than that during the pre-1966 phase.  The spatial picture of
      urban growth also changed somewhat."

PMID- 12179098
TI  - Urban growth in South Asia.

PMID- 12179100
TI  - Demographic development in a developing economy:  a case study of Uttar Pradesh.
AB  - "Patterns of and trends in demographic development in the Indian state of Uttar
      Pradesh have been analysed in this paper.  Indices of urbanisation, literacy and
      occupational structure were used for this purpose.  Their aggregate index
      represented the level of demographic development."  The data are for 242
      subdivisions of Uttar Pradesh for the census years 1971 and 1981.  Particular
      attention is given to regional differentials in demographic indicators.  The
      relationships among economic development and the measurements of literacy,
      urbanization, and occupational status are explored

PMID- 12179099
TI  - Population growth and distribution versus agricultural change:  an analysis of
      the Warli tribal community in Dahanu and Talaseri Talukas of Thane district
      (Maharashtra).
AB  - The authors examine the relationship between population growth and agricultural
      change using a village-level study of the Warli tribal community in Maharashtra,
      India.  "This paper tries to highlight the relationship that exists between the
      two factors and the relative changes in the structural character of the two
      factors.  It also focuses on the complications brought about by the juxtaposition
      of a market economy of the nontribals on the subsistence peasant agriculture of
      the Warli tribals.  Methodology is empirical.  Suitable statistical aids have
      been used on available census material [for the years 1901-1971], substantiated
      with fieldwork."

PMID- 12179102
TI  - The experiences of women refugees in Kenya.

PMID- 12179101
TI  - The role of women in internal migration in Zambia.

PMID- 12179103
TI  - Life must go on in northern Uganda, but what price are the women paying?

PMID- 12179104
TI  - Let us break the silence surrounding women victims!

PMID- 12179105
TI  - The Democratic Republic of Congo: a country raped by all types of men.

PMID- 12179106
TI  - Cambodia: the women want justice and peace.

PMID- 12179107
TI  - Documenting women's experiences: displaced women in Bweyale (central Uganda).

PMID- 12179108
TI  - A case study of Ore women victims of Biafra war in Nigeria between 1966 to 1970.

PMID- 12179109
TI  - Women's experiences in the armed conflict situation in Sudan.

PMID- 12179110
TI  - Dissolution of marital couples in Czechoslovakia and some of its consequences.

PMID- 12179111
TI  - [Recent trends in divorce in France:  some comparisons with the Czechoslovak
      republics].

PMID- 12179112
TI  - [Trends in first marriages from 1961 to 1988].

PMID- 12179113
TI  - [The control of reproduction:  contraception and abortion in France and
      Czechoslovakia].

PMID- 12179114
TI  - [Thirty-five years of family formation in France.  Trends in legal marriage and
      in the creation of new couples].

PMID- 12179115
TI  - [New reproductive behavior:  the cases of France and the Czech Republic].

PMID- 12179116
TI  - [Mortality projections based on current or cohort mortality rates].

PMID- 12179117
TI  - [A complex approach to accepting hypotheses for the projection of natality].

PMID- 12179118
TI  - [Population and household projections by the Federal Statistical Office of the
      Czechoslovak Socialist Republic].

PMID- 12179119
TI  - [Geographic origin of newlyweds and projections of migration].

PMID- 12179120
TI  - [Some experiences in long-term population projections in Czechoslovakia].

PMID- 12179121
TI  - [Block model of the family structure and its application].

PMID- 12179122
TI  - [Some methodological aspects of projecting the labor force and employment].

PMID- 12179123
TI  - [Ethnic aspect of demographic developments in the determination of the future
      size of the population of a region].

PMID- 12179125
TI  - [The questions of complex socio-demographic projections].

PMID- 12179124
TI  - [Social policies as a basis for demographic projections].

PMID- 12179126
TI  - [Development of the methodology of fertility projections for the population of
      Yugoslavia: a retrospective view].

PMID- 12179127
TI  - [Questions of forecasting fertility].

PMID- 12179128
TI  - [An additive or multiplicative fertility model?].

PMID- 12179129
TI  - [Analysis of the relationship between the weight of the infant at birth, newborn
      infant mortality, and the social structure of the population of Czechoslovakia
      from the viewpoint of future population projections].

PMID- 12179130
TI  - [Numerical methods of periodization and projection of natural movement of the
      population of Czechoslovakia in the years 1949-1972].

PMID- 12179131
TI  - [Projecting natality trends with the use of a system of factors].

PMID- 12179132
TI  - [Some questions of the relationships between urban development and migration].

PMID- 12179133
TI  - [Projections of population migration].

PMID- 12179134
TI  - [Social and economic prerequisites of migration and projection of population
      movement].

PMID- 12179135
TI  - [Some questions of projection modeling of regional population structures].

PMID- 12179137
TI  - [Some methodological problems in developing models of demographic projections].

PMID- 12179136
TI  - [Trends in migration processes in the USSR].

PMID- 12179138
TI  - [Main theoretical and methodological principles in the projection of demographic
      processes].

PMID- 12179139
TI  - [Demographic aspects of the theory and practice of mass housing construction].

PMID- 12179140
TI  - [Transformation of the family structure for the purposes of special prognoses].

PMID- 12179141
TI  - [Some approaches to the calculation of future sizes of the family].

PMID- 12179142
TI  - [Canonical model of the development of the family in the Armenian Soviet
      Socialist Republic].

PMID- 12179143
TI  - [Demographic projections of urban centers as a reference for planning the
      distribution of households and apartment sizes].

PMID- 12179144
TI  - [Projections and concepts of urbanization in Socialist countries].

PMID- 12179145
TI  - [Some methodological questions in projecting the labor force in the Polish
      People's Republic].

PMID- 12179146
TI  - [Projections of employment by industries].

PMID- 12179147
TI  - [Projection of urban labor force].

PMID- 12179149
TI  - [The concept of tables of educational attainment].

PMID- 12179148
TI  - [Determination of retirement eligibility and retirees].

PMID- 12179150
TI  - [Model of direction of the school system (demographic projection model)].

PMID- 12179151
TI  - [Demographic aspects of crime projections].

PMID- 12179152
TI  - [Techniques of demographic projections and their improvements].

PMID- 12179153
TI  - [Regional demographic projections in general plans of urban developments].

PMID- 12179154
TI  - [The significance and problems of demographic projections for localities in
      Yugoslavia].

PMID- 12179155
TI  - [Regional projection from the viewpoint of a planned economy].

PMID- 12179156
TI  - [Demographic characteristics of the southeast macroregion of Poland and problems
      of demographic research in macroregional planning].

PMID- 12179157
TI  - [Conditions required for the demographic projections of towns].

PMID- 12179158
TI  - [Some aspects of population projections in Poland].

PMID- 12179159
TI  - [Demographic projections in the management and planning of a school system at the
      district level].

PMID- 12179160
TI  - [Basic tendencies  of population growth in the USSR].

PMID- 12179161
TI  - [Economic development as a foundation for population growth].

PMID- 12179162
TI  - [Possibilities of demographic projections and the complexity of demographic
      transformations].

PMID- 12179163
TI  - [Demographic projections in the plans of social development of territorial
      units].

PMID- 12179164
TI  - [Some relationships between population projections and social policies].

PMID- 12179165
TI  - [Social indicators and projections of social phenomena].

PMID- 12179166
TI  - [Theoretical principles of socio-demographic projections].

PMID- 12179167
TI  - [The role and significance of demographic projections in socioeconomic
      development].

PMID- 12179168
TI  - Women use illicit drug to induce abortion.

PMID- 12179169
TI  - IMA to conduct training courses in family planning.
AB  - For the last six and a half decades, the Indian Medical Association (IMA) has
      been actively engaged in Public Health issues, ranging from immunization, ORT,
      maternal and child health care, and has been cooperating with the Government of
      India in various National Health Programs.  Recently, IMA organized a new and
      exciting program on India's most significantly health issue--family planning. 
      The training is to be competency based and participatory, with the main emphasis
      on knowledge, attitude and skills required to provide comprehensive child
      spacing. IMA has developed this multilevel program to train personnel in all
      methods of family planning, like:  participation in basic oral contraceptive
      training; supplementary training in other methods; clinical practice for
      providing information on how to select and manage non-clinical family planning
      services; simulated practice in IUCD; and clinical practice in IUCD training. 
      Training can also be arranged for vasectomy practicum and minilaparotomy.  The
      main purpose of the training program is to realize the Government's goal of 60%
      contraceptive prevalence usage by the year 2000.  In India, less than 2% of the
      132.5 million reproductives, couples use oral contraceptives, because of
      widespread misconceptions regarding the pill among the general populace and the
      medical community.  This program has been designed to counter these misgivings
      and thus encourage the "use of modern family planning methods" to take on the
      menace of the population explosion.

PMID- 12179170
TI  - TB back with a vengeance.

PMID- 12179171
TI  - Safe motherhood: priority in S Asia.

PMID- 12179172
TI  - Measles is down but not out.

PMID- 12179173
TI  - Health ministry guidelines on measles immunisation.

PMID- 12179174
TI  - Certain anti-diarrhoeals to go off the shelf.

PMID- 12179175
TI  - Laparoscopic surgery -- a revolution in the field of gynecology.

PMID- 12179176
TI  - To conquer TB, patients must take their medicine.

PMID- 12179177
TI  - The social roots of urban tuberculosis.

PMID- 12179178
TI  - Estrogen's protection against heart disease may be overstated.

PMID- 12179179
TI  - Public health communications for safe motherhood.

PMID- 12179181
TI  - International Conference on Population and Development.

PMID- 12179180
TI  - Charging the vas deferens -- a novel male contraceptive method.

PMID- 12179182
TI  - Polio eradication nearing its conclusion, but not yet.

PMID- 12179183
TI  - Planning sex of baby -- the Barthakur method.

PMID- 12179184
TI  - Pregnancy possible after organ transplant.
AB  - Despite past concerns to the contrary, women who have had an organ transplant can
      become pregnant, and their chances of having a healthy baby are good, researchers
      at the University of Pittsburgh Medical Center say.  There has been concern that
      the drugs given to suppress the body's rejection of transplanted organs might
      increase the risk of premature birth, low birthweight or other complications.  In
      the new study, the researchers studied 14 pregnancies in 12 liver-transplant
      recipients given the anti-rejection drug FK506.  7 of the 12 women delivered
      their babies vaginally, and more than half of the mothers were able to carry
      their babies to the full term.  Of the 14 babies in the study, 12 are alive and
      well.  2 babies were born prematurely and died soon after birth.  The rest were
      born without birth defects or evidence of infection--a concern because FK506
      crosses the placenta and may suppress the baby's immune system.  The mothers were
      advised against breast feeding, since FK506 is excreted in breast milk, and the
      effect of chronic exposure on babies is not known. In 1993, approximately 18,000
      transplants were performed in the US and 3441 of them were liver transplants. 
      About 46% of liver transplants recipients were women.

PMID- 12179185
TI  - Obstacles impede development of contraceptive vaccine.

PMID- 12179186
TI  - Immuno-contraception undergoing promising trials.

PMID- 12179187
TI  - Depo-Provera -- proving its innocence.

PMID- 12179188
TI  - Breast-feeding may reduce breast-cancer risk.

PMID- 12179189
TI  - Anaemia -- a major cause of maternal death.

PMID- 12179190
TI  - Strong solution required for maximum reach of ORT.

PMID- 12179191
TI  - Good health -- the future scenario.

PMID- 12179192
TI  - Progestogens in gynaecological practice.

PMID- 12179193
TI  - Gender discrimination weighs heavily down on babies.

PMID- 12179194
TI  - Asia-Pacific AIDS incidence on the rise.

PMID- 12179195
TI  - Time to take a stand.

PMID- 12179197
TI  - Effective, despite misconceptions. The IUD with progesterone must be replaced
      once a year, while the IUD with copper may be left in for up to 10 years.
AB  - Many women have misconceptions about the intrauterine device, or IUD.  The IUD is
      a safe and effective contraceptive method for many women.  It is more effective
      than the condom, diaphragm, or spermicides, and also is more convenient than
      these methods, since it doesn't interfere with different sexual activities.  The
      IUD is a small, T-shaped plastic device containing either copper or progesterone,
      and is inserted by a doctor into a woman's uterus.  A thin plastic thread (1-2
      inches long) protrudes through the cervix so that the user can cross-check to
      make sure the device is in place.  Depending on the IUD type, small amounts of
      copper or progesterone are slowly released to prevent fertilization of the egg,
      or to prevent a fertilized egg from attaching to the uterine wall.  The IUD with
      progesterone must be replaced once a year, while the IUD with copper may be left
      in for up to 10 years.  The IUD is a good choice for women who can't take oral
      contraceptives and for women who have completed their families but want surgical
      sterilization.  Because the IUD carries a slightly higher risk of ectopic
      pregnancy (a fertilized egg that implants outside the uterus), it is not usually
      recommended for women who already are at increased risk of the condition, such as
      those who have had a pelvic infection, a previous ectopic pregnancy or multiple
      sex partners.  Common side effects of the IUD include some discomfort while the
      IUD is being inserted and some cramping and spotting during the first few weeks
      after insertion.  Menstrual periods usually become slightly longer and heavier in
      women using the copper IUD, but become lighter in women using the progesterone
      IUD.  Occasionally, the IUD will slip partially out of the uterus or be expelled
      entirely in the first few months.

PMID- 12179196
TI  - Contraception options shrinking -- US expert.

PMID- 12179198
TI  - Green signal for sex.
AB  - Thought to be at least as reliable as condoms, the world's first electronic
      contraceptive expected to go on sale this year displays a green light when it is
      safe to have sex.  Independent experts supervising trials of the Unipath Personal
      Contraceptive System say it could transform family planning, offering millions of
      women an alternative to the pill with no risk to health.  It is not a physical
      contraceptive and provides computer-guided advice on when to abstain from sex. 
      Conversely, it is also seen as an aid to those women who are trying to become
      pregnant, because it acts as an accurate fertility indicator.  During the past
      year, the system developed by Unipath, the medical division of Unilever, has been
      tested by 1500 women in Europe.  Preliminary results suggest that its reliability
      falls between that of condoms, which the WHO says are 88% safe on average, and
      the pill (98.2%).  Unipath plans to charge about 80 pounds plus another pound for
      a month's supply of sticks.  The Family Planning Association, which praised the
      system, expressed reservations about the cost and did not see it "knocking the
      pill off its perch."  John Guillebaud, Medical Director, Margaret Pyke Family
      Planning Center in London, said: "It could be as good as the condom, but will be
      very unforgiving if the user breaks the rules."

PMID- 12179199
TI  - A constitution for AIDS.

PMID- 12179200
TI  - Maternal mortality -- revised WHO estimates alarming.

PMID- 12179201
TI  - Breast-fed infants' growth charts.

PMID- 12179202
TI  - Tubal sterilisation -- a practical option.

PMID- 12179203
TI  - Abortion rate expected to soar -- contraceptives, not ban the answer.

PMID- 12179205
TI  - Quinacrine acceptance spreads at NAVSFWI meet.

PMID- 12179204
TI  - HIV-infection in the US, Canada, India and Thailand.

PMID- 12179206
TI  - Polio elimination in India thru' PPI.

PMID- 12179208
TI  - Sterilisation without surgery.

PMID- 12179207
TI  - "Kangaroo care" helps preemies.

PMID- 12179209
TI  - MMR and its control.

PMID- 12179210
TI  - Short-course ciproflox treatment of acute uncomplicated UTI in women.

PMID- 12179211
TI  - Uproar over Milk Substitutes Act.

PMID- 12179212
TI  - Gianotti-Crosti syndrome and HIV infection.

PMID- 12179213
TI  - The polio story -- great on the whole but shabby in patches.

PMID- 12179214
TI  - Checking population -- a national priority.

PMID- 12179215
TI  - Health care providers can prevent and treat PID.

PMID- 12179216
TI  - US company supplies defective Copper-Ts.

PMID- 12179217
TI  - Pulse immunization -- polio eradication strategy.

PMID- 12179218
TI  - Zidovudine improves psoriasis in HIV-positive males.

PMID- 12179219
TI  - HIV, drug use, unsafe sex -- bad news.

PMID- 12179220
TI  - The World Summit for Social Development.

PMID- 12179221
TI  - The family planning methods.

PMID- 12179222
TI  - Breast is best.

PMID- 12179223
TI  - The Philippine medium-term plan for human development.

PMID- 12179224
TI  - Human development?

PMID- 12179225
TI  - Family planning saves lives and P303 billion for the Philippine government.

PMID- 12179226
TI  - The demographic impact of the Philippine family planning program: a tale of two
      Metro Manilas.

PMID- 12179227
TI  - In search of a better life.

PMID- 12179228
TI  - Celebrating its 25th anniversary, UNFPA presents Today's Choices for Tomorrow's
      World.

PMID- 12179230
TI  - State of the World's Children.

PMID- 12179229
TI  - Philippine population policy: quo vadis?

PMID- 12179231
TI  - AIDS: there's hope.

PMID- 12179232
TI  - Let us look at the population issue unflinchingly.

PMID- 12179233
TI  - Social attitudes of Filipinos towards family planning interest groups.

PMID- 12179234
TI  - Population pressures: threat to democracy.

PMID- 12179235
TI  - The future is urban.

PMID- 12179236
TI  - Sustaining a world in balance.

PMID- 12179237
TI  - Has the Philippines backed into a demographic trap?

PMID- 12179238
TI  - Philippine laws and policies on the status of women.

PMID- 12179239
TI  - Human suffering.

PMID- 12179240
TI  - Demography.

PMID- 12179241
TI  - Population and annual renewable fresh water availability: selected countries,
      1955-2050.

PMID- 12179242
TI  - The State of the World's Children 1993. The age of neglect may be giving way to
      an age of concern.

PMID- 12179243
TI  - Of all the planet's renewable resources, fresh water may be the most unforgiving.

PMID- 12179244
TI  - Global carrying capacity: how many people?

PMID- 12179245
TI  - [The AIDS epidemic in the Ukraine].

PMID- 12179247
TI  - [The NGOs together].

PMID- 12179246
TI  - [Lithuania: the need for a better intergovernmental collaboration].

PMID- 12179248
TI  - [Has Russia gotten worse?].

PMID- 12179249
TI  - [The campaign against AIDS in Africa: the potential role of South Africa].

PMID- 12179251
TI  - [AIDS in Russia. It is still possible to stop the epidemic. Interview with Dr.
      A.P. Koslov].

PMID- 12179250
TI  - [The SidAlerte network: what's new?].

PMID- 12179252
TI  - [Contraceptive efficacy].

PMID- 12179253
TI  - [Centers attended by young people: many promises and good prospects].

PMID- 12179254
TI  - [Interview with Manuela Sampaio].

PMID- 12179255
TI  - [On the Cairo polemic: a comparative perspective].

PMID- 12179256
TI  - [Block project I].

PMID- 12179257
TI  - [Non-contraceptive benefits of contraception].

PMID- 12179259
TI  - [APF. Open letter to the political parties, on the abortion situation in
      Portugal].

PMID- 12179258
TI  - [Norplant, new method of contraception in Portugal].

PMID- 12179260
TI  - [The Beijing conference: a controversy and new challenges].

PMID- 12179261
TI  - [Postpartum contraception].

PMID- 12179262
TI  - [Sexuality, health promotion and the educational process. Key ideas about an
      intervention and its repercussions].

PMID- 12179263
TI  - [From maternal-child health to the achievement of autonomy].

PMID- 12179265
TI  - [Demographic aging and family planning: what relationship].

PMID- 12179264
TI  - [IPPF declaration on breast feeding, fertility and postpartum contraception].

PMID- 12179266
TI  - [Casal Ventoso: the need to discover other ways of living].

PMID- 12179267
TI  - [Oral contraceptives: APF takes a position].

PMID- 12179268
TI  - [Sharing motivation and training experiences in the area of sexuality. Interview
      with Antonio Cardoso Ferreira].

PMID- 12179270
TI  - [Law 6/84: "an inappropriate law"].

PMID- 12179269
TI  - [Time to be young].

PMID- 12179271
TI  - Maternal mortality at the University of Benin Teaching Hospital Benin City,
      Nigeria.

PMID- 12179272
TI  - Maternal death in the booked and unbooked patients: University of Port Harcourt
      Teaching Hospital experience.

PMID- 12179273
TI  - Yearly trends in caesarean section and cesarean mortality at Ile-Ife, Nigeria.

PMID- 12179275
TI  - Opening addresses.

PMID- 12179274
TI  - Preventable factors in abortion-related maternal mortality in Africa: focus on
      abortion deaths in Benin City, Nigeria.
AB  - In a 13-year review of maternal deaths of the University of Benin Teaching
      Hospital, Benin City, abortion was one of the 3 major causes of death, accounting
      for 37 (22.4) out of 165 deaths.  Induced abortion was responsible for 34 (91.9%)
      of these deaths.  The usual victim is the teenage and inexperienced school girl
      who has no ready access to contraceptive practice.  Death  was mainly due to
      sepsis, (including tetanus) hemorrhage, and trauma to vital organs, complication
      directly attributable to faulty techniques by unskilled abortion providers, by-
      product of the present restrictive abortion laws.  Total overhaul of maternal
      child health services and family health education system, as well as integration
      of planned parenthood at primary health care level into the health care delivery
      system, are suggested.  Contraceptive practice should be made available to all
      categories of women at risk and the cost subsidized by governmental and
      institutional bodies.  Where unwanted pregnancies occur, the authors advocate
      termination in appropriate health institutions where lethal and sometimes fatal
      complications are unlikely to occur.  In effect, from the results of this study
      and review of studies on abortion deaths in Nigeria and other developing
      countries, it is obvious that a revision of abortion laws as they operate,
      notable, in the African continent, is overdue.

PMID- 12179276
TI  - Training traditional birth attendants reduces maternal mortality and morbidity.

PMID- 12179277
TI  - Maternity care monitoring (MCM): implications for practice, research, and medical
      education.

PMID- 12179278
TI  - The consecutive management of uterine rupture.

PMID- 12179280
TI  - Hazard of vaginal delivery after two previous caesarean sections.

PMID- 12179279
TI  - Outcome of labour in African short women.

PMID- 12179281
TI  - Uterine aspiration using the Karman cannula and syringe.

PMID- 12179282
TI  - Maternal mortality at Ilorin, Nigeria.

PMID- 12179283
TI  - Maternal mortality at the University of Nigeria Teaching Hospital, Enugu: a 10
      year survey.

PMID- 12179284
TI  - Maternal mortality from emergency caesarean section in booked hospital patients
      at the University of Nigeria Teaching Hospital Enugu.

PMID- 12179285
TI  - Maternal mortality in Ghana: is there a place for traditional birth attendants
      (TBAs) as reporters of maternal mortality-related data?

PMID- 12179286
TI  - Maternity care monitoring: the case of the unbooked patient.

PMID- 12179287
TI  - The influence of antenatal care on pregnancy outcome.

PMID- 12179290
TI  - [The world of demographers].

PMID- 12179288
TI  - Biosocial factors in maternal mortality: a study from a Nigerian mission
      hospital.

PMID- 12179289
TI  - Maternal mortality--a sharper focus on a major issue of our time.

PMID- 12179291
TI  - [Foreigners in the Netherlands:  a statistical-demographic approach].
AB  - "Following an explanation of the difficulties of outlining a statistical picture
      of the groups of foreigners present in the Netherlands that is reliable from all
      points of view, estimates for 1971, 1979 and 1980 are presented.  The significant
      growth that emerges from this picture is principally accounted for by the groups
      from the so-called recruitment countries and from Surinam.  In the last few years
      the birth-rate of non-Netherlands allochtones staying in the Netherlands has
      shown a clear increase, partly as the result of increasing immigration for the
      purpose of family reunion."

PMID- 12179292
TI  - [Aspects of population in the 1980 state budget].

PMID- 12179293
TI  - [Functions and activities of the Interdepartmental Commission on Population
      Management].

PMID- 12179294
TI  - [National Program of Demographic Research: program and management].

PMID- 12179296
TI  - [Demography and social planning].

PMID- 12179295
TI  - [Advisory Commission for Population Forecasting].

PMID- 12179297
TI  - [The population factor in the work program of the Scientific Advisory Board for
      Government Policy].

PMID- 12179298
TI  - Children, health and AIDS.

PMID- 12179299
TI  - Child mortality through AIDS.

PMID- 12179300
TI  - Moral and ethical concerns.

PMID- 12179301
TI  - The Catholic Church's response to the pandemic of HIV / AIDS.

PMID- 12179302
TI  - Uganda. TASO: living positively with AIDS.

PMID- 12179303
TI  - Perinatal transmission of HIV in Africa.

PMID- 12179305
TI  - HIV transmission and breast-feeding.

PMID- 12179304
TI  - Nepal: a potentially explosive situation.

PMID- 12179306
TI  - Millions of children stricken by AIDS.

PMID- 12179307
TI  - Philippines: street children, children at risk.

PMID- 12179308
TI  - Brazil: a clinic for street kids.

PMID- 12179309
TI  - AIDS and children: dangers and opportunities.

PMID- 12179310
TI  - Research on AIDS: knowledge, attitudes and practices among street youth.

PMID- 12179311
TI  - Thailand. Sexually exploited children: receivers and transmitters of HIV.

PMID- 12179312
TI  - Nepal: a cultural prostitution.

PMID- 12179313
TI  - Uganda. Assistance programme for AIDS orphans.

PMID- 12179314
TI  - Rwanda. AIDS orphans: problems and solutions.

PMID- 12179315
TI  - Brazil: the children of the day after.

PMID- 12179317
TI  - AIDS education video: Karate Kids.

PMID- 12179316
TI  - Zambia: anti-AIDS clubs.

PMID- 12179318
TI  - Philippines: pilot project on HIV and AIDS education and prevention.
AB  - The project set up by Christian Children's Fund-Philippines and STOP Trafficking
      of Filipinos aims to identify cultural practices of young people which may have
      bearings on their sexual practices and information on how they think and feel
      about HIV and AIDS. The baseline study found that a number of young adults shared
      common misconceptions about boy-girl relationships and sex; therefore, there is a
      need to clarify these concepts and develop self-awareness in order to promote
      sound and healthy attitudes toward interpersonal relationships and sexual
      behaviors. The study also found the need for young people to undergo training as
      a strategy for information dissemination and acquisition of right information
      and/or expand knowledge to deal effectively with current realities including
      HIV/AIDS and human sexuality. This baseline information is used to design
      intervention and communication packages composed of training modules, posters,
      and other materials that can be used for an educational program for youth. This
      project was supported by the National AIDS Prevention and Control Program of the
      Department of Health in the Philippines.

PMID- 12179319
TI  - Education for life: a behaviour process for groups.

PMID- 12179320
TI  - Prevention at school level. Chile: "Education for prevention and non
      discrimination".

PMID- 12179322
TI  - Prevention at school level. UNESCO and WHO: six pilot projects.
AB  - UNESCO (United Nations Educational, Scientific and Cultural Organization) and the
      World Health Organization (WHO) are jointly undertaking six pilot projects in
      Asia and the Pacific, Africa, Latin America and the Caribbean to develop
      innovative approaches for AIDS education in schools, with the long-term objective
      of integrating successful educational strategies into school curricula. The
      projects are being carried out through workshops for the production of educative
      materials and teacher training workshops. The overall goal is to help young
      people of school age behave responsibly, giving rightful importance to self
      esteem and mutual respect. In line with the program's objective of focusing on
      technical leadership and support to help countries plan and implement effective
      AIDS control, plans are underway to organize regional training courses for
      decision makers on AIDS education in school.

PMID- 12179321
TI  - Prevention at school level. Hong Kong: a kit for secondary school teachers.

PMID- 12179323
TI  - Chile: educational game, "Learning about AIDS: the Responsibility of All".

PMID- 12179324
TI  - Social aspects of HIV / AIDS and children.

PMID- 12179325
TI  - [The demography of Arab-Muslim marriage:  tradition and change].

PMID- 12179326
TI  - [The population of Morocco:  past and current trends].

PMID- 12179327
TI  - [Emigration].

PMID- 12179328
TI  - [The forced migration of population inside Lebanon, 1975-1986].

PMID- 12179329
TI  - [The necessity of controlling population growth in Algeria].

PMID- 12179330
TI  - [The Arabian Peninsula: demographic surprises].

PMID- 12179332
TI  - A note on the analytical methods of differential determinants of fertility in
      Bangladesh.
AB  - "This paper aims at making a note on the problems inherent in the analytical
      methods of differential determinants of fertility in Bangladesh. Two approaches
      are there to illustrate the issues. One is to pick up studies that have been
      conducted by different researchers, and make note of the problems from those
      studies. Another one is to pick up a data set and perform the relevant analyses
      to point out the limitations inherent in the methods. The second approach has
      been opted for this exercise.... The standard recode file (BD SRO3) of the
      Bangladesh Fertility Survey...has been used as the data source."

PMID- 12179331
TI  - Differential female mortality and health care in South Asia.

PMID- 12179333
TI  - Rural-urban migration in Bangladesh: theoretical approaches to understanding the
      internal and external dynamics.

PMID- 12179334
TI  - The changes in the French migratory policy and their consequences upon West
      Africa.
AB  - The author discusses French immigration policy, with a focus on migrant streams
      from Western Africa. "The purpose is first to highlight convergent and opposed
      interests between the migratory policy elaborated from 1945 to 1975, during ?the
      glorious [thirty years]', and the African migrants' strategies as well as the
      consequences upon the countries [of origin]. Then, the paper will question the
      effects of those changes both on the immigrants' behaviours and on the countries
      [of origin]...."

PMID- 12179335
TI  - The ghosts of Malthus:  demography and modes of production.

PMID- 12179336
TI  - The economic background of demographic growth.

PMID- 12179338
TI  - Migration and social mobility in Bangladesh: the marginalisation of peasant
      migration.

PMID- 12179337
TI  - Women, work and wages in rural Bangladesh.

PMID- 12179339
TI  - The demographic impact of tubectomy in Bangladesh.

PMID- 12179340
TI  - [Development features of regional population aging in Finland].
AB  - "Population ageing has emerged as one of the crucial problems facing developed
      countries. In Finland, the old population (aged 65 and over) has doubled in
      numbers over the past 30 years. The phenomena underlying this ageing trend
      include a decline in fertility, increase of the average life expectancy, and the
      effects of migration. Considerable regional differences in population ageing can
      be observed between Finland's provinces, municipalities and between their
      different parts.  The number of the elderly is projected to increase in all
      provinces, the highest relative increase taking place in the provinces of
      Lapland, Uusimaa and Oulu between 1990-2020." (SUMMARY IN ENG)

PMID- 12179341
TI  - [Regional identity and regional migration: birth places and present dwelling
      places of the Finns].

PMID- 12179342
TI  - [Statistical indications of ruralization in Finnish towns].

PMID- 12179343
TI  - [Present and future migration research: a critical review].

PMID- 12179344
TI  - [Regional population development in Finland in the 1970s].

PMID- 12179345
TI  - [Birth spacing activities for the year 1991].

PMID- 12179346
TI  - [Survey on the continuity of contraception in Algiers].

PMID- 12179347
TI  - [Birth spacing activities, first trimester, 1992].

PMID- 12179348
TI  - [Birth spacing activities for the year 1992].

PMID- 12179349
TI  - [New data on maternal mortality in India].

PMID- 12179350
TI  - [Residences for pregnant women reduce the risk of obstetrical catastrophies].

PMID- 12179352
TI  - [Community participation promotes immunization].

PMID- 12179351
TI  - [Hepatitis B vaccine: a new force against pandemic diseases].

PMID- 12179354
TI  - [Integration of traditional midwives in primary health care].

PMID- 12179353
TI  - [Monetary incentives for a more effective immunization program].

PMID- 12179355
TI  - Midwives' day launched.

PMID- 12179356
TI  - Managing shoulder dystocia.

PMID- 12179357
TI  - A call for a new approach towards midwifery practice.

PMID- 12179358
TI  - How do I.U.C.D.'s prevent pregnancies? [Answer to question].

PMID- 12179359
TI  - Marching forward. Our view.

PMID- 12179360
TI  - President's corner.

PMID- 12179362
TI  - Your decision to breast feed is best.

PMID- 12179361
TI  - Are you expecting?

PMID- 12179363
TI  - Longer life span for Copper T 380 A.
AB  - Copper T 380 A, the intrauterine device (IUD), has now been clinically approved
      by the US Food and Drug Administration (FDA) to have a longer lifespan. 
      According to a population council news release, the device, which originally had
      a 4-year term duration, has been found out to be effective for 6 years.  The
      extension was based on data from a study conducted by the World Health
      Organization (WHO) and submitted to the FDA by the Population Council, developer
      of the IUD.  This extension will undoubtedly have many advantages, as the less
      frequently the device is replaced, the fewer the risks of pelvic inflammatory
      disease, perforation, and other complications that occur mainly soon after
      insertion.  More so, less frequent insertions will cost less and be more
      convenient.  The president of the Population Council, Mr. George Zeidenstein,
      welcomed the FDA action and said "when we licensed Cynopharma (the sole
      distributors of the product) to introduce the Copper T 380A IUD in the US 3 years
      ago, we knew it was a superior, long-acting reversible method that would expand
      contraceptive options.  The fact that this IUD is approved for 6 years makes it
      an even more attractive option for women choosing a contraceptive method."

PMID- 12179364
TI  - 25 more midwives trained in F.P.
AB  - The 10th day of June 1993 was another day in the life of GRMA as 25 Private
      Midwives were awarded certificates in Family Planning Training. This is the first
      of 8 trainings to be held under the second phase of the Family Planning  Project
      and was held at the Eredec Hotel, Koforidua, from 31st May - 11th June. 
      Participants were drawn from 3 regions:  Eastern 12, Volta 3, and Greater Accra
      10.  They were trained in Counselling of Clients and in the provision of Family
      Planning Services.  The 3 new Trainers for the Association, with the help of the
      Project Director, Ms. Florence Quarcoopome, and Mrs. Charlotte Quimby, a training
      consultant from the US, handled the workshop.  The Deputy Regional Minister, Mr.
      W. B. Asante, who gave the keynote address advised the participants not to waste
      their resources but to put all that they have learnt into practice to help
      mothers and children in Ghana.  The Chairman of the occasion, Dr. Aaron Offei,
      Eastern Regional Deputy Director of Health Services, advised the participants to
      send in their returns correctly and on time.  The participants staged a role play
      on dispelling of rumors in Family Planning.

PMID- 12179365
TI  - Socio-behavioural research by WHO.

PMID- 12179366
TI  - Studies on attitudes and perceptions in Brazzaville.

PMID- 12179367
TI  - Cosmology and change in Rwanda.

PMID- 12179368
TI  - Playing AIDS: an experiment in popular theatre in Mali.
AB  - In Mali, an original experiment called the "useful theater" has succeeded in
      making the population aware of the problem of AIDS while entertaining them at the
      same time. Philippe Dauchez, a French stage director and teacher of dramatic art
      at the Institut National des Arts (INA) in Bamako, drew his inspiration from a
      popular theater tradition, the koteba, and created the "useful theater", whose
      aim is to make messages about health acceptable by presenting them in an amusing
      way. Five companies of actors, all former pupils of INA, regularly visit the most
      far flung villages to present plays on hygiene and especially on AIDS. The AIDS
      question is treated here with humor, though gradually the comedy turns to tragedy
      as one by one, towards the end of the play, the characters learn that they have
      contracted AIDS. The actors mime their convulsions and suffering and die on
      stage, despite the efforts of the healer and the doctor, who remain powerless.
      The aim is to show how the disease is transmitted and how to protect oneself by
      using a condom. After each performance a discussion is organized to make sure
      that the message has truly been understood, and condoms are distributed to the
      audience.

PMID- 12179369
TI  - Training IEC / AIDS activity organizers in schools in Yaounde.

PMID- 12179370
TI  - Voluntary screening and counselling: public health or community health?

PMID- 12179371
TI  - Knowledge, opinions and attitudes towards AIDS in rural Africa (Senegal,
      Cameroon, Burundi). Current research.

PMID- 12179373
TI  - The traditional treatment of AIDS in Uganda: benefits and problems. Key issues
      and debates: traditional healers.

PMID- 12179372
TI  - The role of traditional healers in HIV / AIDS counselling in Kampala, Uganda. Key
      issues and debates: traditional healers.

PMID- 12179375
TI  - Donating blood in the time of AIDS. Some ideas from a study in Bangui (Central
      African Republic). Current research.

PMID- 12179374
TI  - A targetted intervention research on traditional healer perspectives of sexually
      transmitted illnesses in urban Zambia. Current research.

PMID- 12179376
TI  - Special report: South Africa. Coping with AIDS in apartheid's shadow.

PMID- 12179377
TI  - [Increase in population and the standard of living in Java, 1800-1942].

PMID- 12179378
TI  - [Abortion in a Ghanian society].

PMID- 12179379
TI  - [Demographic forecasts:  the composition of the present and future population].

PMID- 12179380
TI  - [Reproduction and survival: family building and population growth in past and
      present].

PMID- 12179381
TI  - [More than 900 million Chinese: the social and economic consequences of China's
      population policy].

PMID- 12179382
TI  - [Population geography].

PMID- 12179383
TI  - Bio-medical aspects of fertility control.

PMID- 12179384
TI  - Voluntary sterilization - a world view.

PMID- 12179385
TI  - The population problem and family planning effort.

PMID- 12179386
TI  - Parity, contraception and infant mortality.

PMID- 12179387
TI  - Family planning; postpartum approach.

PMID- 12179388
TI  - Demographic change in the Arab world: the impact of migration, education and
      taxes in Egypt and Morocco.

PMID- 12179389
TI  - Algeria. From demographic explosion to social rupture.

PMID- 12179390
TI  - Yemeni workers come home: reabsorbing one million migrants.

PMID- 12179391
TI  - Migrants, workers and refugees: the political economy of population movements in
      the Middle East.
AB  - The author investigates causes and consequences of migratory movements in the
      Middle East. "Two factors--integration into the world labor market and the
      fragility of integration within the separate states--largely explain why
      conflicts in the Middle East have in recent years produced the greatest refugee
      flows of any region in the world.... The crisis of the secular nation-state in
      the Middle East will continue as states become either politically or economically
      more dependent on outside protection or assistance. The challenge by Islamist
      movements is also likely to undermine national cohesion by politicizing religious
      identity."

PMID- 12179392
TI  - Devices and desires: population policy and gender roles in the Islamic Republic.

PMID- 12179393
TI  - The challenge of population growth in Morocco.

PMID- 12179394
TI  - [The silences of Cairo].

PMID- 12179395
TI  - [An end to poverty]].

PMID- 12179396
TI  - [Cities in peril, Mahgreb].

PMID- 12179397
TI  - [To be a woman in Africa. On the danger of being a mother. Mortality].

PMID- 12179399
TI  - Keynote address: IGCC Expert Meeting on Comparative Fertility Research
      Sterilization and Post Conceptive Regulation.

PMID- 12179398
TI  - [On the way to Beijing: Dakar Conference].

PMID- 12179400
TI  - Law, policy and the use of non-physicians in family planning service delivery.

PMID- 12179401
TI  - Welcome address [to Workshop/Seminar for More Effective Promotion and Management
      of Integrated Projects (Family Planning and Parasite Control)].

PMID- 12179402
TI  - Closing remarks [to Workshop/Seminar for More Effective Promotion and Management
      of Integrated Projects (Family Planning and Parasite Control)].

PMID- 12179403
TI  - Extracts from the report on the Joint IGCC/IFRP East and South East Asia Seminar
      on Regional Fertility Research.

PMID- 12179404
TI  - [Changes in population distribution in the USSR, 1970-1981].

PMID- 12179405
TI  - [The demographic situation and settlement].

PMID- 12179406
TI  - [Urban dynamics in the decade of the 1980s: concentration of in-migration,
      spatial segregation and social exclusion].

PMID- 12179407
TI  - [Environment, crisis, and development: thoughts on the Ozama and Isabela rivers].

PMID- 12179408
TI  - [Popular education in health and nutrition: literature review].

PMID- 12179410
TI  - [The relationship between economic development and population growth].

PMID- 12179409
TI  - [Situation and current demographic trends in the Dominican Republic].

PMID- 12179411
TI  - [Elements of a better understanding and evaluation of population policy in the
      Dominican Republic].

PMID- 12179412
TI  - [Some aspects of the relationship between population and ecology in the Dominican
      Republic].

PMID- 12179413
TI  - [Policies of economic development and population].

PMID- 12179415
TI  - [Norplant: a new alternative in family planning].

PMID- 12179414
TI  - [Haitian migration to Santo Domingo].

PMID- 12179416
TI  - [Population and education. The educational situation in El Salvador].

PMID- 12179418
TI  - [Reproductive health and family planning are human rights].

PMID- 12179417
TI  - [World Population Day editorial].

PMID- 12179419
TI  - [Population and food scarcity].

PMID- 12179420
TI  - [Equality between men and women is a right].

PMID- 12179421
TI  - [Excessive population and health].

PMID- 12179422
TI  - [Deforestation and overpopulation].

PMID- 12179423
TI  - [Promotion of the legal right to family planning].

PMID- 12179424
TI  - All India Women's Conference Seminar on Habitat II and Human Settlement.

PMID- 12179425
TI  - Women in search of identity.

PMID- 12179426
TI  - Gender equality and women empowerment.

PMID- 12179428
TI  - Literacy -- one woman at a time.

PMID- 12179427
TI  - About "Save the Children Committee (India)".

PMID- 12179429
TI  - A summary of the recommendations adopted unanimously at the Fourth World
      Conference on Women (4-15 September 1995).

PMID- 12179430
TI  - The case for greater Australian support for population issues.

PMID- 12179431
TI  - Issues in population planning: the case of Papua New Guinea.

PMID- 12179432
TI  - Family planning education: working with target groups in the South Pacific.

PMID- 12179433
TI  - Population paradoxes.

PMID- 12179434
TI  - Population: a red herring in the environment debate.

PMID- 12179435
TI  - Population and environment: an Australian challenge.

PMID- 12179436
TI  - Population and Australian development assistance.

PMID- 12179437
TI  - Global population growth.

PMID- 12179438
TI  - HIV, development and unhealthy institutions.

PMID- 12179439
TI  - HIV / AIDS, human rights and development.

PMID- 12179440
TI  - Migrants and HIV / AIDS.

PMID- 12179441
TI  - Incorporating social capital into development practice: the HIV epidemic.

PMID- 12179442
TI  - HIV and technology: the issue of prophylactic vaccines.

PMID- 12179443
TI  - Australia's international response to HIV / AIDS.

PMID- 12179444
TI  - The HIV / AIDS epidemic in India: are we doing enough?

PMID- 12179445
TI  - Hope, paradox and the politics of suspicion: confronting latter-day AIDS in
      Thailand.

PMID- 12179446
TI  - Reproductive health rights and women with HIV in Thailand.

PMID- 12179447
TI  - HIV vulnerability and mobile populations: Thailand and its borders.

PMID- 12179448
TI  - Introduction: HIV and development.

PMID- 12179449
TI  - The challenge of HIV spread among and from injecting drug users in Asia.

PMID- 12179450
TI  - Harm reduction, HIV and development.

PMID- 12179451
TI  - Strategies for dealing with HIV / AIDS in the former Soviet Union.

PMID- 12179452
TI  - AIDS: a nightmare ingredient in the Indonesian development broth.

PMID- 12179454
TI  - HIV and development the Papua New Guinea way.

PMID- 12179453
TI  - Sex talk, Indonesian youth and HIV / AIDS.

PMID- 12179455
TI  - Should HIV be on the development agenda?

PMID- 12179456
TI  - The sociocultural and economic context of HIV / AIDS in Papua New Guinea.

PMID- 12179457
TI  - Safe sex or healthy sex?

PMID- 12179458
TI  - Young people, HIV / AIDS, and intervention: barriers and gateways to behaviour
      change.

PMID- 12179459
TI  - A national disaster: a social analysis of AIDS in Zimbabwe.

PMID- 12179460
TI  - The socioeconomic implications of HIV / AIDS in sub-Saharan Africa.

PMID- 12179461
TI  - Fiscal and monetary policies in the South Pacific Island countries: an
      evaluation.

PMID- 12179462
TI  - Development, governance and drugs.

PMID- 12179463
TI  - Mugabe: victim of the IMF and World Bank?

PMID- 12179464
TI  - Collaboration in the provision of family health education in Swaziland.

PMID- 12179465
TI  - Linking HIV / AIDS to development.

PMID- 12179466
TI  - Using drama to target risky behaviours in Papua New Guinea.

PMID- 12179467
TI  - Child survival--the survival of a perinate.

PMID- 12179468
TI  - Health services system in India: an expression of socio-economic inequalities.

PMID- 12179469
TI  - Local health traditions.

PMID- 12179470
TI  - Many ways of community health.

PMID- 12179471
TI  - Political economy of western medicine in third world countries.

PMID- 12179472
TI  - Tribal women:  victims of the development process.

PMID- 12179473
TI  - Politics of the birth control programme in India.

PMID- 12179474
TI  - Santhaan. Kaise Rokein? Kaise Payein? A case study of the Patna Natural Family
      Planning Programme.

PMID- 12179475
TI  - The awakening from devastation to development. (A case study of the Diviseema
      Social Service Society (DSSS) in the metamorphosis of the socio-economic
      conditions in the Diviseema, Andhra Pradesh devastated by the cyclonic tidal wave
      of November 1977).

PMID- 12179476
TI  - [A summary of family planning activities during the last three economic and
      social development plans (1974-1986)].

PMID- 12179477
TI  - [Desired family size in Arab countries].

PMID- 12179478
TI  - [Ideal family size in Arab countries].

PMID- 12179479
TI  - [Fertility and contraception in Maghreb].

PMID- 12179480
TI  - [Family planning in Tunisia:  reasons for its success and future strategy].

PMID- 12179481
TI  - [Family planning in Tunisia:  reasons for success and strategies for the future].

PMID- 12179482
TI  - [Socio-ethical considerations in the sex preferences for infants (analysis of a
      pertinent survey of 200 women)].

PMID- 12179483
TI  - [The Tunisian experience in family planning: recorded results].

PMID- 12179485
TI  - [The population situation in the world and in Tunisia: the demographic
      transition].

PMID- 12179484
TI  - [Prospects for family planning in 1991 in Tunisia].

PMID- 12179486
TI  - The changing skill of new immigrants to the United States: recent trends and
      their determinants.
AB  - "The objective of this paper is to describe and understand the determinants of
      changes in the number and quality of new legal immigrants to the United States
      over the last 25 years. Our main interest is in understanding the behavioral
      response of potential immigrants to changes in the U.S. immigration law regime
      (as well as in the origin-country determinants of demand for immigration to the
      United States) and how these affect and have affected the skill composition of
      immigrants.... [The authors] assembled a new data set based on annual INS records
      of all new, legal immigrants over the period 1972 through 1995.... Inspection of
      our new data indicates that since the mid 1980s the average skill of new, U.S.
      legal immigrants has been rising relative to that of the U.S. population. An
      econometric analysis of a panel of country-specific measures of the skill of
      immigrants based on these data over the period 1972-1992 indicates that these
      changes are due in part to changes in immigration law and to the overall rise in
      the real purchasing power of countries outside the United States."

PMID- 12179487
TI  - Coding geographic areas across census years: creating consistent definitions of
      metropolitan areas.
AB  - "This paper presents suggested matches for the geographical coding (geocoding) of
      metropolitan areas in the 1970, 1980, and 1990 Censuses.  The Census Bureau used
      different definitions and taxonomies to describe the geography of metropolitan
      areas in these three Census years. As a result, the geographical areas referred
      to by the standard Census Bureau definitions differ among the three Census data
      sets. The geographic matching scheme explained in this paper attempts to maximize
      consistency over time for metropolitan areas in the U.S."

PMID- 12179488
TI  - Population age structure and asset returns: an empirical investigation.
AB  - "This paper investigates the association between population age structure,
      particularly the share of the population in the 'prime saving years' 45-60, and
      the returns on stocks and bonds. The paper is motivated by the claim that the
      aging of the 'Baby Boom' cohort in the United States is a key factor in
      explaining the recent rise in asset values. It also addresses the associated
      claim that asset prices will decline when this large cohort reaches retirement
      age and begins to reduce its asset holdings. This paper begins by considering
      household age-asset accumulation profiles. Data from the Survey of Consumer
      Finances suggest that while cross-sectional age-wealth profiles peak for
      households in their early 60s, cohort data on the asset ownership of the same
      households show a much less pronounced peak.... The paper then considers the
      historical relationship between demographic structure and real returns on
      Treasury bills, long-term government bonds, and corporate stock. The results do
      not suggest any robust relationship between demographic structure and asset
      returns.... The paper concludes by discussing factors such as international
      capital flows and forward-looking behavior on the part of market participants
      that could weaken the relationship between age structure and asset returns in a
      single nation."

PMID- 12179489
TI  - Immigration and welfare magnets.
AB  - "This paper investigates if the location choices made by immigrants when they
      arrive in the United States are influenced by the interstate dispersion in
      welfare benefits. Income-maximizing behavior implies that foreign-born welfare
      recipients unlike their native-born counterparts, may be clustered in the states
      that offer the highest benefits. The empirical analysis indicates that immigrant
      welfare recipients are indeed more heavily clustered in high-benefit states than
      the immigrants who do not receive welfare, or than natives. As a result, the
      welfare participation rate of immigrants is much more sensitive to changes in
      welfare benefits than that of natives."

PMID- 12179490
TI  - Demographics and medical care spending: standard and non-standard effects.
AB  - "In this paper, [the authors] examine the effects of likely demographic changes
      on medical spending for the elderly. Standard forecasts highlight the potential
      for greater life expectancy to increase costs: medical costs generally increase
      with age, and greater life expectancy means that more of the elderly will be in
      the older age groups. Two factors work in the other direction, however. First,
      increases in life expectancy mean that a smaller share of the elderly will be in
      the last year of life, when medical costs generally are very high.... Second,
      disability rates among the surviving population have been declining in recent
      years by 0.5 to 1.5 percent annually.... Thus, changes in disability and
      mortality should, on net, reduce average medical spending on the elderly.
      However, these effects are not as large as the projected increase in medical
      spending stemming from increases in overall medical costs."

PMID- 12179491
TI  - Malthus to Solow.
AB  - "A unified growth theory is developed that accounts for the roughly constant
      living standards displayed by world economies prior to 1800 as well as the
      growing living standards exhibited by modern industrial economies. Our theory
      also explains the industrial revolution, which is the transition from an era when
      per capita incomes are stagnant to one with sustained growth.... [The authors]
      use a standard growth model with...[several] technologies. The first, denoted the
      'Malthus' technology, requires land, labor and reproducible capital as inputs. 
      The second, denoted the 'Solow' technology, does not require land. [The authors]
      show that in the early stages of development, only the Malthus technology is used
      and, due to population growth, living standards are stagnant despite
      technological progress. Eventually, technological progress causes the Solow
      technology to become profitable and both technologies are employed. At this
      point, living standards improve since population growth has less influence on per
      capita income growth.  In the limit, the economy behaves like a standard Solow
      growth model."

PMID- 12179493
TI  - Migration and pension.
AB  - "Migration has important implications for the financial soundness of the pension
      system.... While it is common sense to expect that young migrants, even if low
      skilled, can help society pay the benefits to the currently elderly, it may
      nevertheless be reasonable to argue that these migrants would adversely affect
      current young since, after all, the migrants are net beneficiaries of the welfare
      state. In contrast to the adverse effects of low skilled migration in a static
      model, [the authors] show that in a Samuelsonian overlapping generations
      model...migration is a Pareto-improving measure. All the existing income (low and
      high) and age (young and old) groups living at the time of the migrant's arrival
      would be better off."

PMID- 12179492
TI  - The educational attainment of immigrants: trends and implications.
AB  - "This paper uses the 1970, 1980, and 1990 U.S. Censuses to study trends in
      educational attainment of immigrants relative to natives. Immigrants have become
      relatively less highly educated, but have become more highly educated in an
      absolute sense. The effects of changes in relative educational attainment between
      immigrants and natives on earnings are studied. Educational differences are found
      to explain more than half the observed wage gap between the two groups. The paper
      also allows for non-linearities in returns to education. Sheepskin effects
      influence earnings in different ways for natives and immigrants.  Differences in
      returns to pre- and post-migration education also appear. The paper also finds
      evidence that immigrants crowd natives out of education, although the effects are
      stronger in secondary than in postsecondary education."

PMID- 12179494
TI  - [Population dynamics of the rural Colombian population: 1951-1985].

PMID- 12179495
TI  - [The demographic transition in Colombia and its social and economic
      consequences].

PMID- 12179496
TI  - [Population dynamics and population projections for the country, national
      territories, Bogota, departments, and 30 major cities:  methodological aspects
      and main results].

PMID- 12179497
TI  - [The demographic transition in Colombia and its social and economic
      consequences].

PMID- 12179498
TI  - [Socioeconomic factors as determinants of mortality from malaria in Colombia].

PMID- 12179500
TI  - [The demographic transition in Colombia: determinants and socioeconomic impact].

PMID- 12179499
TI  - [Fertility decline in Colombia:  expression of a profound social change].

PMID- 12179501
TI  - [Bogota:  recent trends (toward the polarization of urban centers or
      metropolitanization?)].

PMID- 12179503
TI  - Allaying the fears in the use of intrauterine devices.

PMID- 12179502
TI  - NDHS pins high infant mortality on malnutrition.

PMID- 12179504
TI  - Family planning and PHC programme.

PMID- 12179505
TI  - Family planning and PHC programme.

PMID- 12179506
TI  - Planning your family safely.

PMID- 12179507
TI  - Mobilizing resources for maternal and child health. Workshop report.

PMID- 12179508
TI  - Family planning: what women say.

PMID- 12179510
TI  - How large is wrong?

PMID- 12179509
TI  - The myth about contraceptives and breast cancer.

PMID- 12179511
TI  - Threat of number.

PMID- 12179513
TI  - Yes, father, but.

PMID- 12179512
TI  - Planners in dark tunnel.

PMID- 12179514
TI  - On the slow lane. Family planning campaign now catches on in Nigeria.

PMID- 12179516
TI  - [Urban growth in Spain, 1950-1991. The end of a process with negative
      consequences for the territorial balance].

PMID- 12179515
TI  - [Spain.  Regional differences in population density in 1986:  the end of a
      process of increasing internal disequilibrium?].

PMID- 12179517
TI  - [Six billion people: how the continents were populated--yesterday, today, and
      tomorrow].

PMID- 12179518
TI  - [The Nigerian demographic problem: the political and economic issues at stake].

PMID- 12179519
TI  - [The 1975 census and the position of Seine-et-Marne in the population of the
      Paris region].

PMID- 12179520
TI  - Deprivation in London wards:  mortality and unemployment trends in the 1980's.
AB  - "This paper describes the use of current estimates of population and economic
      activity for London's wards in developing small area social indicators.  The
      particular focus is on changes in the spatial pattern of mortality and
      unemployment differences in the 1980s in relation to the wider incidence of
      deprivation in wards.  A conditional model of change is developed for mortality
      and unemployment indices to assess whether spatial differences are widening over
      time and how far changes in these indices are linked to social class and
      deprivation.  The evidence is of widening unemployment differences, and a slight
      widening in premature mortality."

PMID- 12179522
TI  - The evaluation of the 1980 decennial census.

PMID- 12179521
TI  - Aspects of general linear modelling of migration.
AB  - "This paper investigates the application of general linear modelling principles
      to analysing migration flows between areas.  Particular attention is paid to
      specifying the form of the regression and error components, and the nature of
      departures from Poisson randomness.  Extensions to take account of spatial and
      temporal correlation are discussed as well as constrained estimation.  The issue
      of specification bears on the testing of migration theories, and assessing the
      role migration plays in job and housing markets:  the direction and significance
      of the effects of economic variates on migration depends on the specification of
      the statistical model.  The application is in the context of migration in London
      and South East England in the 1970s and 1980s."

PMID- 12179523
TI  - Evaluation programme of the 1976 census of population and housing: a sampling.

PMID- 12179524
TI  - On sampling frames in African censuses and surveys.

PMID- 12179525
TI  - Conference on the Transition of Fertility in Latin America: Buenos Aires,
      Argentina, April 3-6, 1990.
AB  - This is a report of a conference on the transition of fertility in Latin America,
      held in Buenos Aires, Argentina, in April 1990.  "The main objective of the
      seminar [was] to study in depth the nature, causes and consequences of the
      fertility transition in the countries of the region, with particular emphasis on
      recent developments and the current situation."  The seminar consisted of seven
      sessions covering an overview of the fertility transition, patterns of fertility
      change, determinants of fertility change, factors related to fertility behavior,
      the consequences of fertility decline, fertility in Argentina, and a panel
      discussion.

PMID- 12179526
TI  - IUSSP activities. Committee on Fertility and Family Planning. Research Programme,
      Liege, Belgium, May 25-27, 1995.

PMID- 12179527
TI  - IUSSP activities. Committee on Historical Demography. Report: Conference on Asian
      Population History, Taipei, Taiwan, 4-8 January 1996.

PMID- 12179528
TI  - IUSSP activities: Committee on Fertility and Family Planning. Implications of the
      International Conference on Population and Development (ICPD) Programme of Action
      for the IUSSP.

PMID- 12179529
TI  - Marking the end of the twentieth century. A suggestion for an IUSSP project on
      the millenium.

PMID- 12179530
TI  - The uses of demographic knowledge for policies and planning in developing
      countries:  problems and issues.

PMID- 12179531
TI  - Historical demography in China:  review and perspective.
AB  - "This paper argues that the development of historical demography in China will
      not only contribute greatly to our understanding of the particular population and
      social development dynamics in China, but will also enhance our understanding of
      the role of population for social and economic development in general.... After a
      review of the recent development of population studies in China, this paper will
      review the current state of Chinese historical demography and examine some
      research issues and data sources which can help broaden the horizons of
      population research in China."

PMID- 12179532
TI  - IUSSP activities. Committee on Anthropological Demography. Report: Seminar on
      Fertility and the Male Life Cycle in the Era of Fertility Decline, Zacatecas,
      Mexico, 13-16 November 1995.

PMID- 12179533
TI  - The formal demography of families and households:  an overview.
AB  - "The objective of the present paper is to give a brief overview of the subject
      matter of the formal demography of the family.  Selected references are included,
      but no attempt is made to be exhaustive.  No discussion of socio-economic
      determinants or consequences is included, because this overview is limited to the
      formal aspects of the field.  "The...paper is divided into five parts.  The first
      deals with the descriptive analysis of family and household size and composition,
      from both a cross-sectional and a longitudinal perspective.  The next two
      sections discuss, in order, demographic determinants and consequences.  This is
      followed by a brief section on projection methods and the conclusion."

PMID- 12179534
TI  - Economic consequences of population size, structure and growth.

PMID- 12179535
TI  - Mortality transition in the third world countries:  issues for research.

PMID- 12179536
TI  - The status of women, population and development.

PMID- 12179537
TI  - Seminar on the use of demographic knowledge for population policy formulation in
      Latin America.  Lima, Peru, 14-17 January 1986.  An overview.
AB  - The author reports on a seminar on the application of demographic knowledge to
      population policy in Latin America.  "In the absence of reliable empirical
      evidence, the actual objective of the seminar became an exploration, with Brazil,
      Mexico, Peru and Bolivia as case studies, of questions such as:  what
      applications, what knowledge, what relationships, what emphases, what
      transmission mechanisms, what communication channels, what investment by public
      and private agencies are needed to respond to the demand--actual and potential-
      for demographic knowledge for policy purposes."  The seminar brought together not
      only academics, but parliamentarians, members of international agencies, and
      other professionals concerned with population issues.  The focus of the
      discussion was on ways and means of improving existing flows of information and
      of expanding knowledge available for policy purposes.

PMID- 12179538
TI  - Seminar on adult mortality and orphanhood in the past: five Latin American cases.
AB  - This report concerns a seminar on adult mortality and orphanhood in the past in
      Latin America that was held in San Jose, Costa Rica, December 12-14, 1984.  The
      first part describes five historical studies presented at the seminar concerning
      Mexico, Chile, Peru, Brazil, and Argentina.  "The second part of this article is
      an explanation of the calculation involved in a life table derived from
      information on the incidence of orphanhood according to the age of newly married
      couples on their marriage."

PMID- 12179539
TI  - [Immigration to Italy from Eastern Europe].

PMID- 12179540
TI  - [The need for coordination among the countries of Southeast Asia].

PMID- 12179541
TI  - [A convergence of objectives at the International Conference on Population].

PMID- 12179542
TI  - [Population policy in developing countries].

PMID- 12179543
TI  - [The urban explosion in the third world].

PMID- 12179544
TI  - Bill: PM responds to Jayalalitha's plea.

PMID- 12179545
TI  - New plan to prevent female infanticide mooted.

PMID- 12179546
TI  - Children: a soft target.

PMID- 12179547
TI  - "Creating awareness about HIV / AIDS, the only solution".

PMID- 12179548
TI  - AIDS control: TN may show the way.

PMID- 12179549
TI  - Sustainable development and quality health care.
AB  - On the occasion of Development Week in Canada, Dr. Remi Sogunro spoke in
      February, 1994, about the many achievements of quality primary health care and
      PLAN's strategy to achieve sustainability. In one generation, under-5 mortality
      has been cut by a third. Deaths from measles has been reduced from 2.5 million to
      1 million a year.  Skeletal deformities from polio also have been reduced from
      1/2 million to less than 140,000.  Despite all this, there is much more to be
      attained.  35,000 children under 5 die from preventable diseases every day in
      developing countries.  The health community is working hard to address these
      silent emergencies. PLAN International's primary health care program targets the
      poor and undeserved populations where diseases are prevalent.  The main focus of
      PLAN's programs are mothers and children who are most vulnerable to disease.  Key
      interventions that PLAN gives priority to are childhood and maternal immunization
      programs, including pre- and post-natal care for mothers.  Other interventions
      under PLAN's comprehensive primary health care program include:  control of
      diarrheal diseases and acute respiratory infections, growth monitoring, nutrition
      and control of STDs and HIV/AIDS infection, water and sanitation, family planning
      information and educational services, and rehabilitation of the handicapped.  "Go
      in search of people, begin with what they know, build on what they have," goes a
      Chinese proverb.  This also summarizes PLAN's guiding principle for achieving
      sustainable development:  the importance of investing in people.  PLAN's programs
      in the field build partnerships and empower communities.  PLAN's emphasis on
      institution-building and capacity-building with local institutions is an
      important part of organizational strategy to ensure sustained development.

PMID- 12179550
TI  - CHWs trained in ARI management.
AB  - Regular supervision and refresher trainings were the key to the success of a CHW
      (community health worker) training program in rural Bolivia.  Since 1988, with
      the support of PLAN International, volunteer CHWs have been trained in 115
      villages in Sucre, a rural health area lacking adequate health centers.  CHWs
      educate the community, diagnose and treat pneumonia and refer severe cases to
      health centers or hospitals.  CHWs who were already working on diarrheal disease
      control were chosen for the acute respiratory infection (ARI) case management
      training.  A 3-day training program was organized for individual CHWs in their
      own homes and communities.  The course included practicing on real ARI cases
      under the trainer's supervision.  Since the program started, community respect
      for CHWs has risen.  In one remote village, community leaders reported a marked
      improvement in child survival.  Factors which explain the positive effects of
      CHWs include: a limited number of clearly defined tasks, provision of one-on-one
      appropriate training, periodic refresher courses, and continuous supervision. 
      The main problems have been a lack of constant supply of essential drugs and some
      CHWs over-diagnosing pneumonia.  However, once diagnosis is made, CHWs are
      careful about giving the correct antibiotic doses and instructions to mothers. 
      Refresher training and supervision have helped to correct these initial problems.
      PLAN International and the Ministry of Health have organized supervision and
      training meetings every 2 months.  The CHWs bring to these meetings reports of
      children treated and referred. Case management is analyzed, resupply of essential
      medicines is arranged and those with special problems are scheduled for a
      supervisory visit.

PMID- 12179551
TI  - One third of thirteen million.

PMID- 12179552
TI  - Malaria.

PMID- 12179553
TI  - Focusing on: HIV / AIDS. Workshop addresses world epidemic. Field office
      representatives convene in Khon Kaen.

PMID- 12179554
TI  - And in Kenya, an ambitious effort: AIDS cases multiplying despite attacks on
      problem.

PMID- 12179555
TI  - Mother-to-child HIV-1 transmission.

PMID- 12179558
TI  - Curing a diseased health system.

PMID- 12179557
TI  - AIDS orphans burden extended families. Zimbabwe survey finds that relatives
      struggle to care for surviving children.

PMID- 12179556
TI  - Applying research to AIDS programs in villages. Burkina Faso project learns from
      community survey.

PMID- 12179559
TI  - PLAN Bicol, Philippines: health manpower development program in action.

PMID- 12179560
TI  - Indigenous concepts useful in programs. Experiences in the Bolivian highlands.

PMID- 12179561
TI  - Significant improvements in children's health.

PMID- 12179562
TI  - What is child survival? Child-focused strategy forms key element of PLAN's health
      policy.

PMID- 12179563
TI  - Still-Birth Definition Act 1992 [16 March 1992].

PMID- 12179564
TI  - Child Support Act 1991. [25 July 1991].

PMID- 12179565
TI  - Age of Legal Capacity (Scotland) Act 1991. [Excerpt. 25 July 1991].

PMID- 12179566
TI  - Sexual Offences (Amendment) Act 1992 [16 March 1992].

PMID- 12179567
TI  - Sexual Offences Act 1993 [20 July 1993].

PMID- 12179568
TI  - Human Fertilisation and Embryology (Disclosure of Information) Act 1992 [16 July
      1992].

PMID- 12179569
TI  - Trade Union Reform and Employment Rights Act 1993 [1 July 1993].

PMID- 12179570
TI  - The Employment Standards Amendment Act (2) [14 December 1990].

PMID- 12179571
TI  - Maintenance Enforcement Act 1991. [Excerpt. 27 June 1991].

PMID- 12179572
TI  - Analysis of survival data with multiple causes of failure: a comparison of hazard
      and logistic-regression models with application in demography.
AB  - "The purpose of the paper is to compare results of estimation and inference
      concerning covariate effects as obtained from two approaches to the analysis of
      survival data with multiple causes of failure. The first approach involves a
      dynamic model for the cause-specific hazard rate. The second is based on a static
      logistic regression model for the conditional probability of having had an event
      of interest. The influence of sociodemographic characteristics on the rate of
      family initiation and, more importantly, on the choice between marriage and
      cohabitation as a first union, is examined. We found that results, generally, are
      similar across the methods considered. Some issues in relation to censoring
      mechanisms and independence among causes of failure are discussed."

PMID- 12179573
TI  - The cultural convergence of Korean immigrants in Hawaii: an empirical test of a
      mathematical theory.

PMID- 12179574
TI  - Why do cohabiting couples marry? An example of a causal event history approach to
      interdependent systems.
AB  - The purpose of this paper is to demonstrate a causal approach to interdependent
      systems based on two empirical investigations. These examples demonstrate 1) the
      study of two highly interdependent processes: entry into first marriage as the
      dependent process and the process of first birth/first pregnancy as the
      explaining one; 2) an interdependence occurring mainly in a very specific phase
      of individuals' lives (i.e., during the period of first family formation); 3) the
      involvement of time lags between cause and its effect (e.g., time until detection
      of conception); and 4) the highly dynamic character of an unfolding effect over
      time (i.e., the effect of first pregnancy/first birth on first marriage strongly
      depends on the progress of pregnancy and the time since the birth has taken
      place).

PMID- 12179575
TI  - On some methodological problems in selecting a locality for human migration
      study.

PMID- 12179576
TI  - Causal modeling in international migration research:  a methodological
      prolegomenon.

PMID- 12179577
TI  - A demoeconomic model of the rural sector.

PMID- 12179578
TI  - [Studies on male sterilization: acceptability, effectiveness technology; and
      complications].

PMID- 12179579
TI  - An overview of male sterilization.

PMID- 12179580
TI  - An observation on sperm disappearance from the ejaculate following vasectomy.

PMID- 12179581
TI  - Studies of vasovasostomy: 2. anastomosis of the vas deferens.

PMID- 12179582
TI  - Studies on Vasectomy. IX. Current status of reversible vas occlusion method.

PMID- 12179583
TI  - The method of expected number of deaths, 1786-1886-1986.
AB  - "The method of expected number of deaths is an integral part of standardization
      of vital rates, which is one of the oldest statistical techniques.  The expected
      number of deaths was calculated in 18th century actuarial mathematics...but the
      method seems to have been forgotten, and was reinvented in connection with 19th
      century studies of geographical and occupational variations of mortality.... It
      is noted that standardization of rates is intimately connected to the study of
      relative mortality, and a short description of very recent developments in the
      methodology of that area is included." (SUMMARY IN FRE)

PMID- 12179584
TI  - Problems of selecting a plausible fertility measure for Addis Ababa (based on the
      1984 census data).

PMID- 12179585
TI  - Emerging population issues in Africa.
AB  - "The rate of population growth in Africa has increased significantly because of
      large decreases in mortality without significant decline in fertility rates.  The
      factors leading to high fertility rates are explored as are the social issues
      that result because of the high proportion of children.  Further, although
      mortality rates in Africa have been improving, they continue to lag behind the
      rest of the world.  Some of the reasons behind these and other aspects of the
      demographic situation are explored." (SUMMARY IN FRE)

PMID- 12179586
TI  - U.S. cancer death rates:  a simple adjustment for urbanization.

PMID- 12179587
TI  - Administrative records and surveys as basis for statistics on international
      labour migration.

PMID- 12179588
TI  - Reducing costs of censuses in Norway through use of administrative registers.
AB  - "For some years it has been the policy of Statistics Norway to collaborate with
      various governmental agencies in order to use administrative registers in
      statistics production. This policy has been supported politically, and a new
      Statistics Act has been useful in these efforts. The purpose of this paper is to
      present the strategy and methodology used to produce statistics in general,
      census statistics in particular, when based on a combined use of administrative
      registers and directly collected data. Experiences from Norwegian censuses since
      1960 will be presented."

PMID- 12179590
TI  - Postcensal estimates for local areas using current samples with census as the
      source of sampling frame.
AB  - "Two techniques for direct postcensal local area estimation are introduced in
      this paper.  Compared with existing techniques for postcensal local area
      estimation, the proposed techniques are not subject to any bias due to the
      assumption of constancy of certain statistical relationships between the variable
      of interest and the symptomatic or associated variables established at a certain
      point in time (typically a census)."  The author notes that "application of the
      proposed techniques calls for recognition of an integrated design approach at the
      early planning stage, incorporating considerations of survey designs for the
      census and the postcensal sample surveys, maintenance and upkeep of the census
      sampling frame, data analysis and local area estimation requirements
      simultaneously.  When the current samples are continuous and overlap each other,
      a third technique for postcensal local area estimation is also proposed.  An
      example illustrating these techniques in estimating postcensal district
      population in Hong Kong is given."  (summary in FRE)

PMID- 12179589
TI  - Developing a census data system in China.

PMID- 12179591
TI  - Computer methods in population census data processing.
AB  - "The paper summarises the findings of an international survey of census
      processing methods used in the 1990 round.  Extensive use is made of computers,
      although the technologies involved vary considerably from country to country. 
      There is more extensive discussion of the use made of computer-assisted and
      automatic coding, non-keyboard data entry methods and the establishment of
      population databases." The geographical scope is worldwide. (SUMMARY IN FRE)

PMID- 12179592
TI  - Multipopulation survey designs:  five types with seven shared aspects.
AB  - "Five types of multipopulation surveys are defined and described: periodic
      surveys; multidomain designs; multinational survey designs; cumulated and
      combined samples; and controlled observations or quasi- experimental designs.  I
      emphasize the deliberate designs of these surveys, not the mere post hoc or ad
      hoc utilization of survey results. Most importantly, I emphasize a sharp
      distinction between seven listed aspects.  Similarity and standardization of the
      survey aspects (definitions, methods, measurements) are essential to avoid biases
      in comparisons, though admittedly difficult.  In contrast, flexibility in
      sampling designs and sizes, to reduce variances, is permissible, also desirable
      to reduce variances and costs." (SUMMARY IN FRE)

PMID- 12179594
TI  - Some sources of nonsampling errors in African census and survey work:  a review.
AB  - "The paper is a review of some of the more common sources of nonsampling errors
      in African census and survey work illustrated by some country experiences.  [The
      author suggests] that development and sustainment of an ongoing Integrated System
      of Household Surveys under the auspices of the United Nations National Household
      Survey Capability Programme may go a long way toward monitoring and controlling
      these and other errors that arise in the said census and survey work."  (summary
      in FRE)

PMID- 12179593
TI  - An analysis of sampling errors for the Demographic Health Surveys.
AB  - "Sampling errors and design effects from 48 nationally representative surveys
      conducted under the Demographic and Health Surveys Program for a large number of
      variables concerning fertility, family planning, fertility intentions, child
      health and mortality etc. are analysed for the total sample, and for urban-rural
      domains, sub-national regions and various demographic and socio-economic
      subclasses.... At the country level, overall design effect (the ratio of actual
      to simple random sampling standard error) averaged over all variables and
      countries is around 1.5. Variation among countries is high, but less so than
      among variables. Urban-rural and regional differentials in design effects are
      small, and can be attributed to the fact that similar sample designs and cluster
      sizes were used across those domains within each country.  Design effects for
      estimates over other subclasses are smaller, and tend towards 1.0 for small
      subclasses and differences, apart from the effect of sample weights which tends
      to persist undiminished across variables and subclasses." (SUMMARY IN FRE)

PMID- 12179595
TI  - Alternative dual system network estimators.
AB  - "When there are two or more data systems and none of them enumerates the
      population at an acceptable completeness level, concern about the bias due to
      underenumeration suggests an estimator which makes joint use of data compiled by
      the combined imperfect data systems.  Conventional dual system estimators are
      based on the existence of two separate data collection systems.  Dual system
      network estimators assume a main survey and a follow-up quality check survey. 
      The main survey adopts a multiplicity counting rule that combines two mutually
      exclusive partial counting rules."  Three dual system network estimators are
      presented.  "One was previously proposed by Sirken (1979) and is the natural
      analogue of the conventional dual system estimator.  The two other estimators are
      proposed as potential improvements, although neither of them is the natural
      analogue of the conventional dual system estimator.  The design effects of the
      three estimators are compared analytically and empirically with one another, and
      with those of the single system conventional and network estimators."  (summary
      in FRE)

PMID- 12179596
TI  - China's experiences in the quality control of its 1982 population census.
AB  - The author reports on experiences with China's 1982 census, which covered
      approximately one billion people and 19 census items.  It is noted that "the
      postenumeration sample survey indicates that the quality of the census
      enumeration is: 0.071% of overcounts and 0.056% of undercounts.  The paper
      presents principles governing quality control in the population census and
      explains a series of quality control procedures adopted to reduce possible errors
      originating in census planning, enumeration and data processing."

PMID- 12179597
TI  - Intervention in the tobacco habits of rural Indian women.

PMID- 12179599
TI  - Smoking control strategies in developing countries: report of a WHO Expert
      Committee.

PMID- 12179598
TI  - Cigarette smoking among Beijing (Peking) high schoolers.

PMID- 12179600
TI  - Smoking among Maoris and other minorities in New Zealand.

PMID- 12179601
TI  - Smoking or health: the Brazilian option.

PMID- 12179602
TI  - Dark tobacco and lung cancer in Cuba.

PMID- 12179603
TI  - Smoking in Malaysia: promotion and control.

PMID- 12179604
TI  - Smoking in Africa: the coming epidemic.

PMID- 12179605
TI  - World population prospects: 1988.

PMID- 12179606
TI  - Projected fertility and contraceptive use.

PMID- 12179607
TI  - Population trends and policies in the least developed countries.

PMID- 12179608
TI  - The world's refugee populations.

PMID- 12179609
TI  - Selected resolutions and decisions related to population adopted by the Economic
      and Social Council at its second regular session of 1991.

PMID- 12179610
TI  - Resolution adopted by the General Assembly on 21 December 1990. 45/216.
      Population and development.

PMID- 12179611
TI  - Women's education and fertility behaviour.

PMID- 12179614
TI  - Third Expert Group Meeting on Methods of Measuring the Impact of Family Planning
      Programmes on Fertility.

PMID- 12179615
TI  - Adolescent fertility in less developed countries.

PMID- 12179616
TI  - Integrating development and population planning.

PMID- 12179618
TI  - Meeting of the four Expert Groups convened in preparation for the International
      Conference on Population.

PMID- 12179619
TI  - UNFPA reports on 1981: highlights of the year.

PMID- 12179620
TI  - World population prospects: 1982 assessment.

PMID- 12179621
TI  - Current status of research on hormonal contraception in the male.

PMID- 12179622
TI  - Inhibition of progestational activity for fertility regulation.

PMID- 12179623
TI  - Sperm enzyme inhibitors for vaginal and other contraception.

PMID- 12179624
TI  - Current status of antagonistic analogs of LH-RH as a contraceptive method in the
      female.

PMID- 12179625
TI  - Immunological Methods of Fertility Regulation: report of a workshop.

PMID- 12179626
TI  - Transcutaneous male sterilization.

PMID- 12179627
TI  - Do contraceptive methods pose fetal risks?

PMID- 12179628
TI  - Long-acting steroidal contraceptive systems.

PMID- 12179629
TI  - Gossypol: a possible male antifertility agent.  Report of a workshop.

PMID- 12179630
TI  - Female sterilization using chemical agents.

PMID- 12179631
TI  - Current status of plant products reported to inhibit sperm.

PMID- 12179632
TI  - Novel peptides in ovarian follicular fluid: implications for contraceptive
      development.

PMID- 12179633
TI  - Current status of research on sperm antigens: potential applications as
      contraceptive vaccines.

PMID- 12179634
TI  - The etiology of pelvic inflammatory disease.

PMID- 12179635
TI  - Long-acting injectable norethisterone contraceptive system: review of clinical
      studies.

PMID- 12179636
TI  - Methods of monitoring ovarian function and predicting ovulation: summary of a
      meeting.

PMID- 12179637
TI  - Adolescent fathers in urban communities: exploring their needs and role in
      preventing pregnancy.

PMID- 12179638
TI  - Adolescent sexuality and premature parenthood: role of the Black church in
      prevention.

PMID- 12179639
TI  - Improving family planning services to rural adolescents.

PMID- 12179640
TI  - Women's responses to abortion: implications for post-abortion support groups.

PMID- 12179641
TI  - Contraceptive self-efficacy: a primary prevention strategy.
AB  - This paper discusses the development, implementation, and qualitative evaluation
      of an intervention designed to improve contraceptive self-efficacy (CSE) in a
      population at high risk for pregnancy.  In a previous study, a relationship was
      found between CSE and a measure of contraceptive use for sexually active young
      women attending a family planning clinic.  Here, the concept of CSE is further
      developed to identify contraceptive and sexual issues for adolescent males, for
      adolescents who show little or no motivation to obtain or use contraceptives, and
      for those adolescents who would plan to carry a pregnancy to term if they were to
      become pregnant.  Implications are drawn for developing primary prevention
      programs.

PMID- 12179642
TI  - Sexually active adolescents: implication for social work intervention and family
      planning services.

PMID- 12179644
TI  - [Decision of 12 October 1989].

PMID- 12179643
TI  - Successful and unsuccessful contraceptors:  a multivariate typology.
AB  - "The purpose of this study is to develop and test a multivariate,
      multidimensional exploratory model of successful and unsuccessful contraceptive
      use."  The data concern 200 sexually active females who visited an obstetrics and
      gynecology department in Hamilton, Ontario, Canada.  The authors conclude that
      successful contraceptive use has to be seen in a multidimensional context and is
      not simply a problem concerning contraceptive information.  They also conclude
      that early sexual socialization and education, generally in the family setting,
      is important in the development of sexually responsible behavior.

PMID- 12179645
TI  - [Judgment of 26 April 1990].

PMID- 12179646
TI  - [Judgment of 14 February 1991].

PMID- 12179647
TI  - [Judgment of 24 February 1992].

PMID- 12179648
TI  - [Judgment of 3 December 1991].

PMID- 12179649
TI  - Extent of utilization and factors influencing antenatal care in rural Rajshahi.

PMID- 12179650
TI  - Role of male factors in infertility and analysis of semen.

PMID- 12179651
TI  - Obstetric related residual morbidities among the women in Bangladesh.

PMID- 12179652
TI  - Cancer cervix -- a retrospective study.

PMID- 12179653
TI  - Arsenicosis: sex differentials.

PMID- 12179654
TI  - Sexually transmitted diseases among the immigrants seeking jobs abroad.

PMID- 12179656
TI  - Birth defects: prevention of neural tube defects by periconceptional use of folic
      acid and screening.
AB  - Folate deficiency is one of today's most common vitamin deficiencies in women. 
      Women who consume a low level of folate during pregnancy are at risk for poor
      pregnancy outcomes including birth defects.  Birth defects are the leading cause
      of fetal and infant deaths throughout the world.  Neural tube defects comprise a
      major portion of the birth tube defects.  Neural tube defects are common and
      serious malformations that originate early in pregnancy.  Each year in the US,
      about 4000 babies are born with these two most common neural tube defects, spina
      bifida and anencephaly.  Spina bifida is the leading cause of childhood
      paralysis.  Several studies showed that about 70% of the neural tube defects
      could be prevented if all women capable of becoming pregnant consumed 0.4 mg of
      folic acid daily before and during early pregnancy.  This paper reports results
      from various human and animal studies.

PMID- 12179655
TI  - Multiple drug resistant Neisseria gonorrhoeae among females of high risk
      behaviour in Dhaka city.

PMID- 12179657
TI  - A review of reproductive health situation in Bangladesh.

PMID- 12179658
TI  - Access to "Jiggasha program: a family planning communication approach" and its
      exposure to the selected background characteristics.

PMID- 12179659
TI  - HIV / AIDS: response to the pandemic in Bangladesh.

PMID- 12179660
TI  - Sexually transmitted diseases (STD) / reproductive tract infections (RTI)
      including acquired immunodeficiency syndrome (AIDS) / human immunodeficiency
      virus (HIV) infections among the women of reproductive age group: a review.

PMID- 12179661
TI  - Traditional birth attendants (hilots) in the Philippines.

PMID- 12179662
TI  - Reproductive endocrinology and infertility training in the Philippines.

PMID- 12179664
TI  - Hemolytic uremic syndrome in pregnancy.
AB  - A 22-year-old primipara presented with hypertension, anemia, thrombocytopenia and
      elevated liver enzymes.  She was initially managed as a case of HELLP syndrome
      but, with conventional treatment, the expected improvement did not occur.  She
      later developed intractable oliguria and azotemia.  The importance of considering
      hemolytic uremic syndrome, a distinct part of the spectrum of preeclampsia,
      separate from but overlapping with HELLP syndrome, was discussed.  The need for
      vigilance in the management was emphasized since the definitive treatment and
      prognosis differ greatly between the two conditions.

PMID- 12179663
TI  - Endometrial adenocarcinoma coexisting with an intrauterine pregnancy: a case
      report.
AB  - A rare case of adenocarcinoma of the endometrium discovered during curettage for
      incomplete abortion was presented and 12 similar cases in the literature were
      reviewed.  In 7 of the 12 patients, a complication of pregnancy led to the
      discovery of the tumor.  In the remaining five, the pregnancy occurred in
      patients known to have endometrial carcinoma.  Most of the cases were well
      differentiated and minimally invading the myometrium.  The pathophysiology, risk
      factors, diagnosis, treatment, and prognosis were described.

PMID- 12179665
TI  - Extraendometrial mullerian adenosarcoma.
AB  - An unusual case of mullerian adenocarcinoma involving multiple sites--the cervix,
      pelvic peritoneum, and ovary--without involvement of the endometrium is reported.
      This 38-year-old presented with vaginal bleeding and polypoid masses from the
      cervix.  On two occasions, cervical punch biopsies were interpreted as
      endometriosis.  Laparotomy revealed masses in the vesico-uterine space and in the
      cul-de-sac.  Total abdominal hysterectomy with bilateral salpingo-oophorectomy
      was done. Microscopic examination showed benign glandular and malignant stromal
      elements in the specimen from the cervix, left ovary, vesico-uterine and cul-de
      sac masses and intestinal implant. Postoperatively, she was treated with
      radiotherapy.  Pelvic and vaginal recurrences were noted 4 months
      postoperatively. Presently, 12 months postoperatively, the patient is still
      undergoing chemotherapy with vincristine, doxorubicin, and cyclophosphamide.  The
      clinical features, possible origin, problems of diagnosis and management,
      prognostic factors and recurrence patterns of this unusually located tumor are
      discussed.

PMID- 12179666
TI  - A single blind comparative study between Itraconazole and Fluconazole in the one
      day treatment of vulvo-vaginal candidiasis.

PMID- 12179667
TI  - Fasting oral glucose challenge test as a predictor of gestational diabetes
      mellitus.
AB  - Gestational diabetes greatly affects maternal and fetal morbidity. Its early
      detection can make possible prevention of adverse outcomes.  There is great
      controversy, however, regarding the appropriate screening test to accurately
      predict its presence. The universal screening test used, the oral glucose
      challenge test (OGCT), is not exempt from this controversy.  Should it be
      administered in the fasting or fed state?  This paper shows that the sensitivity
      of OGCT administered in the fasting state is 96.6%, much higher than that
      administered in the fed state which is 60%.

PMID- 12179668
TI  - A randomized controlled trial of the efficacy of transcutaneous electrical nerve
      stimulation (TENS) versus lidocaine in the relief of episiotomy pain.
AB  - The aim was to compare the efficacy of transcutaneous electrical nerve
      stimulation (TENS) and local infiltration of 2% lidocaine in the relief of
      episiotomy pain measured using a pain visual analog scale (VAS).  A randomized,
      double blind, controlled clinical trial was conducted from January 1 to May 15,
      1998, in the Labor-Delivery Complex of Chong Hua Hospital, Cebu City.  Skin
      electrodes were attached to two acupoints.  "Shenmen" on the wrist and "hegu" on
      the hand are acupoints for general pain relief and relaxation.  These acupoints
      were stimulated using a nerve stimulator.  Stimulation was started during advance
      labor and discontinued right after episiorrhaphy.  VAS scores were taken during
      certain periods and compared with VAS scores for those using the conventional
      method of 2% lidocaine infiltration into the episiotomy site.  There were 68
      patients who met the inclusion criteria.  38 in the TENS group and 30 in the
      Control group.  The patients profile of the two groups did not differ
      significantly in terms of age, age of gestation, parity, and length of
      episiotomy. Among those with VAS score of 5 (bearable), 37% was failed TENS,
      requiring rescue anesthesia.  The proportion of patients with pain during
      episiotomy and 12 hours after episiorrhaphy showed no significant difference
      between the two groups.  But during episiorrhaphy and 1 hour after episiorrhaphy,
      the TENS group was superior to the lidocaine group, with p-values of 0.05 (0.0392
      and 0.0063, respectively) based on the Mann Whitney U-Test. Ambulation time was
      shorter in the TENS group.  Episiotomy tenderness was nil in the TENS group. 
      There was no swelling and edema in the perineum of patients in the TENS.  The
      need for oral analgesics was likewise much lower in the TENS group.  TENS as a
      form of anesthesia-analgesia cannot totally alleviate episiotomy pain as measured
      by VAS scoring system, with 37% as failed TENS. The study showed there was a
      difference only in pain relief during repair, and 1 hour after repair.  With TENS
      being superior to lidocaine, ambulation time was shorter and episiotomy
      tenderness was nil in the TENS group.  Likewise, lesser number of patients
      requested for oral analgesics in the TENS group.

PMID- 12179669
TI  - Admission test as predictor of intrauterine fetal asphyxia.
AB  - This study determined the accuracy of the admission test in predicting
      intrauterine fetal asphyxia.  A total of 229 subjects were included.  The
      admission test, a short continuous electronic fetal monitoring recording, was
      made immediately on admission, on all patients in labor, and was categorized as
      "reassuring", "equivocal", or "ominous".  Intrauterine fetal asphyxia was
      considered to be present when the umbilical cord blood pH was 7.2 and/or the
      Apgar score was 7 at 1 minute; an "ominous" admission test has a high accuracy
      (LR = 8.54) in predicting intrauterine fetal asphyxia, while a "reassuring"
      admission test does not rule out the possibility of asphyxia (LR = 0.39). 
      "Reassuring" tracing is associated with low risk (6.5%) for asphyxia as measured
      by Apgar score and umbilical cord pH, while "ominous" tracing is associated with
      high risk (50%) for asphyxia.  In detecting an umbilical cord pH of 7.2, fetal
      heart rate variability is the most specific (98%), while absence of acceleration
      is the most sensitive (50%).

PMID- 12179670
TI  - First established pregnancy and birth after induction of ovulation with
      recombinant human follicle stimulating hormone during in vitro fertilization
      embryo transfer and intracytoplasmic sperm injection.
AB  - This case report describes the first established pregnancy and birth in the
      Philippines after induction of ovulation with recombinant follicle stimulating
      hormone (rec FSH) during In Vitro Fertilization-Embryo Transfer (IVF-ET) and
      Intracytoplasmic Sperm Injection (ICSI) in a Filipino woman with pelvic
      endometriosis who underwent right oophorectomy for endometrioma 1 year prior to
      IVF-ET and ICSI.  Husband's semenalysis revealed adequate volume with 10% normal
      forms.  Gonadotrophin releasing hormone agonist (Lupron) 375 mg subcutaneous was
      given for 2 cycles.  100 IU B.I.D.  (a total of 2200 IU) of rec FSH was
      administered intramuscularly daily with single preovulatory follicle seen upon
      transvaginal ultrasonographic examination of 10,000 IU of human chorionic
      gonadotrophin, after which a viable singleton pregnancy was revealed at a
      gestational age of 8 weeks.  The course of pregnancy until term was uneventful
      and ended with abdominal delivery at a gestational age of 37.3 weeks secondary to
      poor Fetopelvic Index with oligohydramnios.  A healthy girl was born and
      pediatric examination did not demonstrate any abnormality.

PMID- 12179671
TI  - Updates and controversies in the diagnosis and treatment of CIN.

PMID- 12179672
TI  - Girding for the new millennium.

PMID- 12179673
TI  - Endometrial cancer and surgical staging: a personal assessment.
AB  - In 1998, FIGO introduced a new staging system for endometrial cancer that is now
      surgical rather than clinical.  The addition of extensive lymph node surgery,
      either formal lymphadenectomy or liberal sampling of the pelvic and aortic lymph
      nodes, represents the most significant and controversial component of this
      system. The yield of metastatic nodes is relatively low.  The controversy
      surrounding this staging system are reviewed and some practical options
      considered.

PMID- 12179674
TI  - Takayasu's arteritis and antiphospholipid antibody syndrome in pregnancy.
AB  - This paper reports the first documented case of Takayasu's arteritis and
      antiphospholipid antibody syndrome complicating a pregnancy in a 29-year-old
      gravida-4 para-3 (1200) woman with recurrent fetal losses.  The epidemiology,
      pathophysiology, effects of both diseases on pregnancy, diagnosis and management
      are discussed.  There is a significant relationship between recurrent fetal
      losses and circulating antiphospholipid antibodies; however, there is no such
      relationship between these recurrent fetal losses and Takayasu's arteritis.

PMID- 12179675
TI  - Education for obstetrics and gynecology in the twenty-first century.

PMID- 12179676
TI  - A randomized controlled trial of oxytocin administered at the end of the second
      stage of labor versus oxytocin administered at the end of the third stage of
      labor in the prevention of postpartum hemorrhage.
AB  - The general objective was to determine the incidence of postpartum hemorrhage
      when oxytocin was administered at the end of the second stage of labor compared
      to when oxytocin was administered at the end of the third stage.  The specific
      objectives were to determine the mean amount of blood loss, duration of the third
      stage of labor, need for additional uterotonics and blood transfusion, incidence
      of hypotension and retained placenta, and mean difference in hemoglobin levels. 
      A randomized controlled trial was conducted in a tertiary care training hospital.
      130 women with term, singleton, live pregnancies in cephalic presentation who
      delivered vaginally were included.  Patients were randomly allocated to receive
      oxytocin after the second stage or after the third stage of labor.  Oxytocin was
      administered as a continuous intravenous infusion.  The placenta was delivered by
      controlled cord traction after placental separation.  Blood loss was measured by
      weight, and the corresponding volume was computed.  Relative risk was calculated.
      Incidence of postpartum hemorrhage, volume of blood loss, duration of the third
      stage of labor, need for additional uterotonics and blood transfusion, incidence
      of hypotension and retained placenta, and difference in hemoglobin levels were
      the main outcome measures.  There was a decreased incidence of postpartum
      hemorrhage (39.66% vs. 48.61%, relative risk [RR] = 0.82, 95% confidence interval
      [CI] = 0.55-1.21) and less amount of blood loss (557.93 ml vs. 636.84 ml, p =
      0.352) when oxytocin was administered at the end of the second stage of labor. 
      There was less need for additional uterotonics (12.07% vs. 13.89%, RR = 0.87, 95%
      CI = 0.35-2.14), and blood transfusion (5.17% vs. 5.56%, RR = 0.87, 95% CI = 0.22
      3.99).  There was a smaller mean difference in hemoglobin (16.20 g/dl vs. 20.29
      g/dl, p = 0.145).  Mean duration of the third stage of labor were comparable
      (7.93 minutes vs. 7.96 minutes, p = 0.863).  However, more patients developed
      hypotension (3.45% vs. 1.39%, RR = 2.48, 95% CI = 0.23-26.70).  All results were
      not statistically significant.  There was no incidence of retained placenta. 
      There is a trend towards a reduction of the risk of postpartum hemorrhage when
      oxytocin is administered at the end of the second stage of labor.  This is not
      accompanied by an increased risk for any morbidity.

PMID- 12179677
TI  - Menopausal medicine under difficult conditions: the Philippines.

PMID- 12179678
TI  - Recent activity in Turkey.

PMID- 12179679
TI  - Islam and the small family norm in Bangladesh.

PMID- 12179680
TI  - The International Conference on Population and Development, Cairo Egypt,
      September 5-13, 1994.

PMID- 12179681
TI  - Vasectomy project launched in Turkey. Turkey's first VSC clinic.

PMID- 12179683
TI  - Hillary Clinton visits Pathfinder projects in Brazil.

PMID- 12179682
TI  - Reproductive health program in Vietnam.

PMID- 12179684
TI  - International Planned Parenthood head visits Pathfinder.

PMID- 12179685
TI  - The 1996 election: what it will mean to international family planning.

PMID- 12179686
TI  - Spotlight on Peru.

PMID- 12179687
TI  - Abortion-related issues in the U.S. foreign assistance program.

PMID- 12179688
TI  - Family planning and married fulfillment.

PMID- 12179689
TI  - Family planning and vocations.

PMID- 12179691
TI  - Psychosocial aspects of NFP instruction: a national survey.

PMID- 12179690
TI  - Self-esteem, spiritual well-being, and intimacy: a comparison among couples using
      NFP and oral contraceptives.
AB  - The purpose of this study was to compare the intimacy, spiritual well being
      (SWB), and self-esteem of couples using natural family planning (NFP) with those
      couples using oral contraceptives (OCs).  22 couples who were using the Creighton
      Model Ovulation Method of NFP for 1 year to avoid pregnancy were matched with 22
      couples who were using OCs for a least a 1-year period and administered a SWB,
      self-esteem, and intimacy inventory.  Student t-tests were calculated to
      determine differences in the mean scores of the 3 inventories between the 2
      groups.  The results showed that the NFP couples had statistically higher self
      esteem (T=3.15, p0.01), SWB (T=4.25. p0.001), and intellectual intimacy (T=2.53,
      p0.05) than the OC couples.  There were no differences in emotional, social,
      recreational, and sexual intimacy between the groups.  Although the results
      provide some evidence that NFP can enhance a couple's relationship, other factors
      such as a sampling bias and educational levels could explain the difference.

PMID- 12179692
TI  - A profile of NFP acceptors in Egypt.

PMID- 12179693
TI  - Abortion and moral development theory: listening with different ears.

PMID- 12179694
TI  - Policy and program considerations for teenage pregnancy prevention: a summary for
      policymakers.

PMID- 12179695
TI  - Heterosexuals and HIV transmission: where do we go from here?

PMID- 12179696
TI  - Young women and sexual health.

PMID- 12179697
TI  - The epidemiological situation of HIV / AIDS in Asian and Pacific countries.

PMID- 12179698
TI  - AIDS radio triggers.

PMID- 12179699
TI  - In-flight AIDS videos.

PMID- 12179700
TI  - US refuses to issue entry visas to people with HIV / AIDS.

PMID- 12179701
TI  - Condoms "not used".

PMID- 12179702
TI  - The HIV / AIDS epidemic: the next ten years.

PMID- 12179703
TI  - Socioeconomic, sociodemographic and attitudinal correlates of the tempo of
      divorce.

PMID- 12179705
TI  - The effect of war on marriage, divorce and birth rates.
AB  - The impact of war on marriage, divorce, and birth rates in the United States from
      1933 to 1986 is explored.  The author concludes that "the involvement of the
      nation in military activities was accompanied by a decrease in marriage and birth
      rates but not by any change in divorce rates.  Mobilization of the armed forces
      and demobilization had no discernible impact on divorce, marriage or birth
      rates."

PMID- 12179707
TI  - The impact of unemployment on marriage and divorce.
AB  - "The present study was designed to explore whether unemployment has a deleterious
      impact on family life, resulting in lower rates of marriage and births and higher
      rates of divorce. Time series data were available for twelve nations for the 35
      year period of 1950 to 1985, and the present paper reports analyses of these data
      sets." The results indicate that unemployment is associated with lower marriage
      and birth rates and higher divorce rates.

PMID- 12179706
TI  - Religious homogamy and marital duration among those who file for divorce in
      California, 1966-1971.
AB  - The hypothesis that having a common religion is associated with more stable
      marriages is tested using California data on divorce for the period 1966-1971. 
      The results confirm the hypothesis, and the authors note that "religious homogamy
      among Jewish couples is associated with longer [marriage] duration than any other
      group.  Couples who report no religious affiliation appear to be at greatest risk
      of early filing for divorce.  The religious groupings include the Jewish, the
      Conservative Protestant, the Liberal Protestant, the Roman Catholic and those
      with no religious affiliation."

PMID- 12179708
TI  - Living arrangements after divorce: cohabitation versus remarriage.
AB  - "The purpose of this paper is to examine the characteristics of all [U.S.] couple
      households in which one or both partners were previously married. In this
      examination, we will consider not only households maintained by married
      couples...; we will also consider households formed by cohabiting couples. In
      addition, we will examine the living arrangements of children in these
      households, with particular attention to whether children are from the current
      union or a previous union."

PMID- 12179709
TI  - Trends in divorce and marriage around the world.
AB  - "A study of 27 [developed] nations indicated that divorce rates rose in 25 of the
      nations from 1950 to 1985 while marriage rates declined in 22 of the nations.
      Nations with higher divorce rates in 1950 had steeper increases in the divorce
      rate subsequently, supporting a critical-mass hypothesis."

PMID- 12179710
TI  - Economic consequences of marital dissolution for blacks.
AB  - Paying particular attention to the economic impact of post-divorce on black
      survey respondents of both sexes, "this study analyzes Weitzman's suggestion that
      men and women lose economic well-being in the first year after divorce. Family
      incomes of divorced women and men are compared with [those of] their married
      counterparts for five SES [socioeconomic status] categories. Using t-tests, it
      was found that, for most categories, for both genders, incomes of divorced
      persons were lower than incomes of married persons. Family incomes were regressed
      against a set of four control variables and a marital status variable.  The
      marital status variable was statistically significant for four of the five SES
      categories for females. This was not true for males.  Policy implications are
      considered." The geographical focus is on the United States.

PMID- 12179711
TI  - Teaching sexual education: the experience of a group of housewives in a poor
      neighborhood of Bogota.

PMID- 12179712
TI  - The need for a reproductive health framework: a response to Fred Sai's paper.

PMID- 12179714
TI  - In New York, PrepCom2 drafts ICPD framework. Preparing for the U.N. population
      summit, Cairo 1994.

PMID- 12179713
TI  - What makes a contraceptive acceptable?

PMID- 12179715
TI  - Population. Preparing for the 1994 world conference.

PMID- 12179716
TI  - The population-development tangle. Aspects and actors.

PMID- 12179718
TI  - In Chile, therapeutic abortion still a crime. September 28: Latin American Day
      for Decriminalization of Abortion.

PMID- 12179717
TI  - Abortion: women's demands. Report from Piriapolis.

PMID- 12179719
TI  - Global issues from an African point of view. 7th International Women and Health
      Meeting in Uganda.

PMID- 12179720
TI  - African women's health: an overview from the 7th IWHM.

PMID- 12179721
TI  - Uganda does what it can for women.

PMID- 12179722
TI  - Round table on RU486.

PMID- 12179723
TI  - Campaign for the prevention of maternal mortality and morbidity. Abortion: we
      shall no longer be silent about it] Sixth call for action, International Day of
      Action for Women's Health, May 28, 1993.

PMID- 12179724
TI  - Bringing childbirth back home. Uruguay's "Ayiqueen".

PMID- 12179725
TI  - Latin American and Caribbean Women's Health Network Women and Population Policies
      meeting. Women in decision-making.

PMID- 12179726
TI  - "RU486: Misconceptions, myths and morals." A critique of the criticisms.

PMID- 12179727
TI  - China: ultrasound abuse in sex selection.

PMID- 12179728
TI  - Setting agendas in contraceptive research. Mexico City symposium.

PMID- 12179729
TI  - May 28 International Day of Action for Women's Health.

PMID- 12179730
TI  - The alliance between feminists and researchers. Meeting women's unmet needs.

PMID- 12179731
TI  - Crimes of gender.

PMID- 12179732
TI  - "We need a mechanism to report abuses of women's human rights".

PMID- 12179733
TI  - Adolescent women face triple jeopardy: unwanted pregnancy, HIV / AIDS and unsafe
      abortion.

PMID- 12179734
TI  - Rights of life. Sexuality and reproduction.

PMID- 12179735
TI  - Midwives of the Sertao: the magic of survival.

PMID- 12179736
TI  - Human rights, repression and health meet takes stand on gender-based violence.

PMID- 12179737
TI  - The "ethics" of RU486.

PMID- 12179738
TI  - By and for women. Nicaragua's Si Mujer.

PMID- 12179739
TI  - Women's network in Afghanistan.

PMID- 12179740
TI  - Comparative study on the use of pharmacist advice between U.S. and Korea.

PMID- 12179741
TI  - Individual effects on married women's labor force participation in Korea.

PMID- 12179742
TI  - [[Family development:  a functional choice-making approach based on the National
      Family Planning Program]].

PMID- 12179743
TI  - A cohort analysis of phasic changes in family life cycle as basis for family
      health studies (summary).

PMID- 12179744
TI  - [[Changes in the support system for the aged in Korea]].

PMID- 12179745
TI  - [[Regional and monthly variations in mortality]].
AB  - "Regional and monthly variations in Korean mortality during the period of 1975
      1988 were investigated using vital registration data....A clear regional
      variation in death rates was found, with lower rates in the large cities of Seoul
      and Pusan and [in] two provinces...."  Differences in provincial rates are
      associated with socioeconomic variables and differences in levels of public
      health development.  Changes in seasonal variations in mortality over time are
      noted due to the changing pattern of causes of death from the predominance of
      infectious diseases in the 1970s to chronic and degenerative diseases in the
      1980s. (SUMMARY IN ENG)

PMID- 12179746
TI  - Family development: a functional choice-making approach based on the national
      family planning program. Summary.

PMID- 12179747
TI  - [Changing pattern of National Family Planning and Fertility Survey in Korea].
AB  - The authors review the evolution since the 1960s of South Korea's family planning
      and fertility survey programs. "In the 1960s, research was interested in
      respondents' contraception knowledge and practice rate and in the relationships
      between contraceptive knowledge and the practice rate....[The] major research
      emphasis in the 1970s and 1980s was measuring fertility and finding obstacles or
      problems to family planning projects." Recommendations for future research are
      made. (SUMMARY IN ENG)

PMID- 12179748
TI  - Sex ratio at birth in Korea.

PMID- 12179749
TI  - An overview of the aging population in Korea.
AB  - The author examines demographic aging in South Korea in light of the country's
      near-completion of the demographic transition.  "An attempt is made to describe
      the general features of the present situation of the Korean elderly by reviewing
      several aspects of the aging phenomenon in Korea, namely, the demographic,
      family, psychological, and social welfare aspects."   (SUMMARY IN KOR)

PMID- 12179750
TI  - [A study on socioeconomic factors related to cesarean section in Korea].

PMID- 12179751
TI  - [Determinants of urban obstetrical service utilization in rural pregnant women].

PMID- 12179752
TI  - [Post-nuptial coresidence of married women in Korea].

PMID- 12179753
TI  - [[Family ties of out-migrants: determinants of visiting and paying support to the
      family of origin]].
AB  - "This study investigates the socioeconomic and demographic determinants of [the]
      family ties of out-migrants. Family ties are measured by the frequency of visits
      and the amount of financial support that recent outmigrants pay to their family
      of origin.... Data [are] from the Korean National Migration Survey of 1983...."
      (SUMMARY IN ENG)

PMID- 12179754
TI  - [A study of contraceptive-failure pregnancy and induced abortion in Korea].
AB  - The author reviews South Korea's family planning program since its inception in
      1962.  The focus is on pregnancy due to contraceptive failure and the use of
      induced abortion as a remedy.  It is found that "according to a logistic
      regression analysis, major factors which affect the outcome of pregnancy due to
      contraceptive failure were residence area, number of boys, educational level,
      duration of marriage, women's age and number of children." (SUMMARY IN ENG)

PMID- 12179755
TI  - Interaction between clients and grass-root family planning workers in Korea:
      implications for program performance.

PMID- 12179756
TI  - Analysis of factors contributing to fertility decline in Korea.
AB  - With the successful Korean national family planning program and rapid
      socioeconomic advancement since 1962, the contraceptive prevalence rate has risen
      from 9% in 1964 to 79% in 1991, with the corresponding total fertility rate (TFR)
      going from 6.0 in 1960 to 1.6 in 1988, which is considerably below the
      replacement fertility rate.  The main purpose of this study is, therefore, to
      identify the structural and causal factors that contributed to the fall in
      fertility over the last 3 decades, in an effort to formulate future population
      policy directions and strategies. The 2 methods used for the study were:  the
      standardization approach to examine the structural factors on fertility decline,
      and the bongaarts model to measure the effects of the proximate variables in the
      fertility decline.  The study indicated that the fall in the crude birth rate and
      the general fertility rate for the periods of 1960-70 and 1980-90 were largely
      influenced by the decline in marital fertility which was triggered by the
      national family planning program initiated in 1962. The analysis based on the
      bongaarts model revealed that the 3 principal factors which exercised a strong
      influence on the fertility decline were the rise in age at marriage, the increase
      in induced abortion, and the increase in contraceptive use, but the influence of
      induced abortion has been decreasing in recent years.  In general, the study
      results suggest that the main concerns of the national family planning program
      should be shifted from the past quantitative approach with emphasis on fertility
      reduction to a qualitative approach which stresses maternal and child health and
      other public health programs.

PMID- 12179757
TI  - Changes in the determinants of fertility in Korea: analyses of pregnancy
      intervals and outcomes.
AB  - Korea completed the whole process of what is called the demographic transition to
      a low fertility and mortality level with the successful implementation of the
      national family planning program in 1962, and this has been accompanied by rapid
      socioeconomic development.  Most of the fertility decline was due to a rising age
      at marriage and to lower marital fertility.  The national family planning
      program, combined with the widespread practice of induced abortion, has placed an
      important role in reducing marital fertility, particularly among older women.
      This paper aims, therefore, to examine the determinants of fertility and their
      changes over time in an effort to suggest future population policy directions for
      Korea.  The analysis is divided into 2 parts-estimation of pregnancy intervals by
      applying the proportional hazards model, and estimation of the determinants of
      fertility by adopting the logistic regression model to find out whether a
      pregnancy terminates in a live birth or in an abortion.  In both analyses, the
      sex was included as the main explanatory variable.  A woman's education has been
      shown to have a significant effect on delaying the timing or on the wife's age at
      first pregnancy, but its effect on the pace of subsequent pregnancies is much
      smaller and often positive.  On the other hand, the woman's education has a
      consistently positive effect on the probability of a pregnancy ending in an
      abortion although the effect shows a steady decline over time.  Form first
      parity, the sex composition of previous children stands out consistently as the
      most important factor in deciding both the pace of pregnancy and its outcome. 
      The pregnancy risks of the women with sons are reduced by almost 50% at the
      second and third parities. The probability of a pregnancy ending in an abortion
      also increases substantially when parents already have a son.  The decline of the
      desired family size but the sustained strong son preference has made the sex of
      children a more important factor in the determination of Korean fertility.  The
      woman's education, on the other hand, has become a less important factor.

PMID- 12179759
TI  - Population aging and its health implications in Korea.
AB  - The author discusses the health implications of population aging in the Republic
      of Korea.  "The aging of [the] Korean population, until recently, has remained in
      its early stage, and Korea is expected to enjoy 'a golden period' of lower age
      dependency ratio by the early 2020s. Accordingly, little attention has been
      focused on the health issues and problems associated with these demographic
      changes toward aging in Korea.  But the changing demographic structure...will
      proceed with a relatively high tempo in the next decades.... Therefore it is
      stressed that 'the reserved years' of lower dependency, before population aging
      becomes a substantial public and private burden in Korean demographic context,
      must be fully utilized to formulate effective policies and counter-measures in
      health and welfare sectors, on which the greatest impacts of aging will fall."
      (SUMMARY IN KOR)

PMID- 12179758
TI  - Consequences of rapid fertility decline in the Republic of Korea: issues and
      solutions.
AB  - During the last 3 decades, efforts to deal with population problems in Korea have
      focused largely on reducing population growth.  The national population control
      program has been a major means of achieving this goal.  Between the early 1960s
      and 1990, evidence from a national survey indicates that the percent of current
      use of contraception rose from about 12% to 80% and the total fertility rate fell
      to 1.6. representing 1 of the most rapid fertility transitions in the developing
      world.  In conjunction with this rapid reduction in fertility, mortality also
      improved significantly during this period.  Thus, Korea has virtually completed
      the demographic transition from high birth and death rates to low birth and death
      rates during the same period.  It is widely recognized that Korea has reached
      demographic maturity and has also achieved remarkable economic development at the
      same time.  The world's demographic history shows that the demographic transition
      which almost every industrialized country has gone through from a predominantly
      rural, illiterate society with high birth and death rates, to a predominantly
      rural, illiterate society with high birth and death rates, to a predominantly
      urban, educated society with low birth and death rates usually takes well over a
      century, but in Korea, that process has taken only a few decades.  On the other
      hand, the consequences of a rapid fertility decline bring about various
      demographic and social issues which we have to take into consideration for future
      socioeconomic development policy concerning the well-being of the Korean people. 
      Some of issues for policy consideration can be broadly summarized as follows: 1)
      gradual imbalance of sex ratio at birth due to traditional son preference
      behavior; 2) latent effect of inevitable population aging and increasing
      dependency burden on behalf of the elderly for the public sector; 3) changes in
      family life cycle and rapid transformation form a large to a small family; 4)
      increasing demand for now social roles for women, supported by easing of child
      care burdens within households.

PMID- 12179760
TI  - [An analysis of Korean women's reproductivity].
AB  - An analysis of reproductivity is mainly concerned with the measurement of net
      force of fertility expressed in terms of a generation rather than in a given
      year.  The present study examined current trends of Korean Women's reproductivity
      interpreting general reproduction and net reproduction rates, intrinsic rate of
      natural increase and mean length of gestation.  The data used for this analysis
      were drawn from the national fertility surveys from 1970 through 1990 conducted
      by the Korea Institute for Population and Health.  The figures of the present
      study revealed that the reproduction rates of Korea during the last 20 years
      decreased from 2.22 in 1970 to 0.71 in 1990 and net reproduction rates also
      dropped from 1.9 to 0.69 during the same period of time.  Furthermore, from this
      study, it is noticed that the replacement level of fertility had been reached
      since the early 1980s.  The intrinsic rate of natural increase as measure of
      population growth under existing conditions of fertility and mortality and free
      of the influence of the current age distribution, is computed.  The level of rate
      was not much changed and was 0.3 in 1970 compared with 0.25 in 1990, which is
      still higher than other developed countries.  The mean age of mother at the birth
      of their daughters defined as the length of generation has been slightly changed
      from 23.9 in 1971 to 25.8 in 1990.

PMID- 12179761
TI  - Are labor markets segmented across occupations?

PMID- 12179762
TI  - Population ageing in a selected region of Bangladesh: socio-economic and health
      perspectives.
AB  - "This paper is an attempt to examine the socio-economic-demographic
      characteristics and health status of the aged (60 years and above) in rural
      Bangladesh.... About 87 percent of males are currently married as against only
      half of the females.  On the contrary, a large proportion (50 percent) of females
      are widowed while only 12 percent are widowers.  The educational status of males
      is much better than that of females.... About half of the females are found
      unemployed as against only one-third of males.  As regards the annual income, the
      condition of Hindus is better than that of Muslims.  The majority of the older
      people are living in large households of more than five members."

PMID- 12179763
TI  - Recent changes in the population control policy and its future directions in
      Korea.

PMID- 12179764
TI  - A study on the current contraceptive acceptors' unwanted pregnancy experience.
      Summary.

PMID- 12179765
TI  - [[Changing patterns and projections of headship rates in Korea]].
AB  - "The purpose of this study was to calculate the headship rate for time-series
      analysis,...to review the patterns of changing headship rates and related factors
      and to estimate the headship rates to 2010 [for the Republic of Korea].... The
      data used for this study were derived from the Population and Housing Census
      Reports from 1960 through 1990, U.N. Manual VII and household-related
      literature....[The authors predict that] the total headship rate will maintain a
      uniform pattern of decrease and increase by specific age and peak headship rates
      will gradually extend to younger people.... Rural headship rates will decrease
      steadily and be greatly influenced by age structure.... In addition, the
      difference in headship rates between male and female will be great....Lastly,
      both the divorced and the single will have increasing headship rates for all ages
      [with] the single [having] the most rapid increase rate after their thirties."
      (SUMMARY IN ENG)

PMID- 12179766
TI  - Health status of the elderly and their labor force participation in the
      developing countries along the Asia-Pacific rim.
AB  - The authors examine the health status and labor force participation of and
      support systems for the elderly in developing countries in east, Southeast, and
      south Asia and compare them with Western norms. They find that "there are
      numerous psychological and emotional elements involved in institutionalizing
      support for the elderly, and the marked differences in social and cultural
      factors between the Asian countries and Western industrialized nations make it
      difficult for the former to use...old-age support systems prevailing in the
      latter as a model." (SUMMARY IN KOR)

PMID- 12179768
TI  - [Analysis of contraceptive use: 1968-1991].

PMID- 12179767
TI  - Changes in the determinants of induced abortion in Korea.

PMID- 12179770
TI  - UN lowers projection on future population growth.

PMID- 12179771
TI  - Needs assessment study on adolescent reproductive health and behaviours. Bihar.

PMID- 12179772
TI  - Spel POPDEEDS and A.V. Show in schools.

PMID- 12179773
TI  - NCERT organized a training programme in population and development education for
      state project personnel.

PMID- 12179774
TI  - PPR meeting held: annual review and planning meet.

PMID- 12179775
TI  - International poster contest -- 1998 winning entries awarded.

PMID- 12179776
TI  - [Area differentials of sex imbalance in births].
AB  - Along with a rapid decline in fertility to below replacement levels in South
      Korea, a new demographic phenomenon has emerged: a distorted sex ratio at birth.
      In 1993, the sex ratio was 115.6, with significant differences in this ratio by
      region. "An analysis of national survey data showed that in the areas with the
      most distorted imbalance, people not only have a stronger preference for sons and
      more favoring attitude toward sex-selective induced abortion, but also actually
      have more sex-selective induced abortions after checking the sex of the fetus. 
      This analysis proved that the sex imbalance is being caused by means of sex
      selective induced abortions after checking the sex of the fetus."  (SUMMARY IN
      ENG)

PMID- 12179778
TI  - [Family changes and policy issues in Korea].

PMID- 12179777
TI  - [Factors determining the labor participation rates of married women of different
      income groups].

PMID- 12179779
TI  - [Problem issues of single-parent male-headed families and its policy measures].

PMID- 12179780
TI  - [Racial and gender differences in income before and after retirement in the U.S].

PMID- 12179781
TI  - A method of estimating infant deaths in Korea.
AB  - "The goal of this project was to develop a new method for estimating infant
      deaths in [South] Korea. An attempt was made to collect information on real
      infant death cases by using...medical insurance benefit data and by conducting a
      medical facilities survey, which allows us to [trace] back the fate of the births
      from the delivery.  Another strategy employed was the gathering of information on
      infant deaths from the various existing sources and integrating them into one set
      after adjusting for overlapping cases among the sources." (SUMMARY IN KOR)

PMID- 12179782
TI  - The relationship between sex-ratio and marital behavior.

PMID- 12179783
TI  - [A study of family life cycle of Korean women].

PMID- 12179785
TI  - Testing the cost-effectiveness of three alternative teams in implementing the
      Regional Center for Training (RCT) follow-up system in satellite centers.

PMID- 12179784
TI  - Family planning knowledge and practice.

PMID- 12179786
TI  - Promoting the role of Raidat Riefiat in family planning program (O.R. study).

PMID- 12179787
TI  - National Conference on Findings of Egyptian Maternal and Child Health Survey (7-8
      September 1992).

PMID- 12179788
TI  - Summary on Distinguished Lecturers Symposium and Guest Lectures on Contraception
      (7-8 October 1992).

PMID- 12179789
TI  - Building Development, Food and Population Issues in the Field of Agriculture with
      Rural Development in the Arab Countries (16-21 January 1993). Panel discussion
      (seminar).

PMID- 12179791
TI  - Problems in family planning service delivery systems, and toward an integrated
      rural development program for fertility reduction in rural Egypt.

PMID- 12179790
TI  - Socio-cultural dimensions of population policies in the Third World: the Egyptian
      case.

PMID- 12179792
TI  - Demographic aspects of unemployment in Jordan.

PMID- 12179793
TI  - Estimates of the population of Egypt, 1780-1882.

PMID- 12179794
TI  - Population and development in rural Egypt.

PMID- 12179795
TI  - [Population statistics].

PMID- 12179796
TI  - Acceptability study of the two versus three monthly injectable contraceptives.

PMID- 12179797
TI  - Rationale for an HIV / AIDS prevention and mitigation strategy for Africa:
      combatting the multisectoral impact of the epidemic.
AB  - Unlike most infectious diseases in Africa, HIV/AIDS affects the urban elite as
      well as the rural poor, and generally during their most economically productive
      years.  An increase in deaths among young adults of the magnitude predicted is
      likely to have substantial adverse effects on economic, political, and
      military/security stability throughout Africa.  AIDS is causing increased stress
      on fragile African economic infrastructures as labor productivity declines,
      particularly in agricultural, labor-dependent economies.  AIDS is causing
      obstacles to trade, foreign investment and tourism.  Health systems and social
      coping mechanisms already are overburdened.  High rates of HIV infection among
      police and military personnel threaten internal security. Furthermore, the
      demobilization of military forces in Africa may exacerbate the epidemic when HIV
      infected soldiers return home and spread the virus.  This presentation will
      illustrate why African AIDS Programs must be expanded to mitigate the
      multisectoral impact of the epidemic while preserving its spread.

PMID- 12179798
TI  - Immune response and AIDS.

PMID- 12179799
TI  - Immune system activation boosts HIV replication in HIV-infected people.

PMID- 12179800
TI  - HIV vaccine update. DNA vaccination: a promising candidate for a vaccine against
      HIV-1?

PMID- 12179801
TI  - Africa's battle against HIV: the potential role of South Africa.

PMID- 12179802
TI  - International view on what works in HIV prevention.

PMID- 12179803
TI  - IXth International Conference on AIDS and STDs in Africa (ICASA), Kampala, Uganda
      - December 10-14, 1995.

PMID- 12179804
TI  - Ethical and legal issues.

PMID- 12179805
TI  - The campaign against TB: governments must commit themselves. TB in Africa.

PMID- 12179806
TI  - Tuberculosis and HIV infection in Brazil -- update and overview.

PMID- 12179807
TI  - HIV vaccines advocacy: the role of UNAIDS. Research and accessibility.

PMID- 12179808
TI  - Migration and ethnicity in a non-immigration country: foreigners in a united
      Germany.
AB  - "The re-unification of Germany has dramatically altered the position of settled
      minorities in [the former West Germany]. Ethnic Germans have been granted rights
      hitherto denied to migrant workers and their descendants.  There has been a
      pronounced growth in hostility and violence directed mainly at Turks and
      Yugoslavs.  This has been most evident amongst the former citizens of the [former
      East Germany] and other ethnic Germans. These events have posed anew questions of
      legitimacy which have been answered so far in terms reminiscent of ideologies
      from the Second World War."

PMID- 12179809
TI  - Immigration into Europe and public policy:  do stops really work?
AB  - "Using Italy as a case study, this article explores whether attempts to stop
      immigration can ever be effective.  What it shows is that, contrary to public
      opinion, strict controls are not necessarily effective. Moreover, there is no
      evidence that the position of existing migrants improves when controls are
      increased.  On the contrary, strict controls are associated with undermining the
      position of existing minorities.  Such policies are particularly likely to
      generate the assumption that citizenship rights can only be available on
      ascriptive criteria."

PMID- 12179810
TI  - East-West and European migration in a global context.
AB  - "There is currently a great deal of concern about character and dimensions of
      East-West migration to Europe.  By seeing this movement and potential movement in
      a comparative and historical setting, some understanding of the overall dynamics
      of labour flows in a 150 year period is gained.  Key worldwide migratory
      movements are identified, focusing particularly on migration from Europe to the
      colonies and the U.S. successive periods of migration to Europe and the
      contemporary and projected movements to Europe from the 'East' and the 'South'. 
      The political and social status of the migrants is also assessed."

PMID- 12179811
TI  - The development of policy on denizens in Denmark.
AB  - "This article offers an analysis of Danish migration policy from 1960-90.  The
      framework employed is the Swedish sociologist Thomas Hammar's concentric 'gate'
      model and his concept of 'denizens'. Non-Danish citizens' access to Danish
      society is regulated by 'gates' and security and rights increase in proportion
      with the number of 'gates' passed, culminating in naturalisation and full social,
      legal and political rights. After an initial profile of the various groups of
      foreigners living in Denmark, I discuss the development of policy measures
      regulating immigration with particular reference to the 'Law for Foreigners'. 
      Finally I turn to the critical issue of policy on denizens."

PMID- 12179812
TI  - New employment regimes in cities: the impact on immigrant workers.
AB  - "The major cities of highly developed countries exhibit marked changes in job
      supplies and employment relations. It is frequently held that post-industrial
      societies require plentiful supplies of highly educated workers and will hold no
      openings for the low skilled. It is this latter category of jobs that immigrants
      have tended to fill in recent decades. Empirical data on major cities in advanced
      economies negate this supposition, revealing that there is an ongoing demand for
      immigrant labour and a continuing stream of employment opportunities which do not
      require high educational levels and which pay low wages.  The article examines
      whether this job supply is merely a residue, to some extent augmented by the
      supply of low wage workers themselves, or whether it is a feature of a
      reconfigured labour market in advanced urban economies, i.e. a systemic
      development."

PMID- 12179813
TI  - A continent of migration: European mass migration in the twentieth century.
AB  - "This article gives an overview of the size and geography of migration to and
      within Europe. Changing causes, patterns and trends of international migration,
      as well as key periods, are discussed. It also analyses the composition of
      foreign resident populations in Europe. The article covers the second half of the
      twentieth century. Different types of mass migration as well as links between
      particular sending and receiving countries are analysed. The article also looks
      at public opinion concerning ethnocentric attitudes and the number of foreigners
      in Europe. Finally, policy options are discussed."

PMID- 12179814
TI  - The eastern frontier of Western Europe: mobility in the buffer zone.
AB  - "The post-Communist countries of Poland, Hungary, [and] the Czech and Slovak
      Republics have become a buffer zone between East and West. In this article we
      analyse the way in which this occurs in terms of migration in and out of the
      region. Our analysis focuses upon the emerging role which this region plays in
      relation to other parts of Western and Eastern Europe and the way in which
      economic and political developments there have encouraged particular forms of
      migration. We attempt to build a picture of some of the different kinds of
      migration taking place in relation to the social and ethnic characteristics of
      migrants. The article concludes that these movements are better understood as
      part of the mobility and circulation of people rather than as one-way migration."

PMID- 12179815
TI  - The invisible community: undocumented Polish workers in Athens.
AB  - "This article describes the development of an economic migration from Poland to
      Greece and the creation of a migrant community in Athens. It presents the
      development of a new migration route by political immigrants. It then describes
      how the Polish political emigrants heading for Greece in the mid-1980s
      established the pillar institutions which were inherited by the Polish
      undocumented workers who have followed, and which have served the latter well.
      The article proceeds to highlight the work milieu of the Polish undocumented
      workers in Athens, and discusses the role played by the ?Polish church', i.e.,
      the Roman Catholic church to which Poles were given access. It concludes by
      considering the future prospects of this migration and of the Polish migrant
      community in Greece."

PMID- 12179816
TI  - European migration report.
AB  - "This report uses available statistics to describe the contemporary trends and
      patterns of international migration involving Central and Eastern Europe. It
      focuses on the former Warsaw Pact countries, excluding the former Soviet
      Union..., and also omits former Yugoslavia." The authors conclude that
      "substantial emigration to the West continues, much of it unrecorded. What is
      perhaps more surprising is that the region has emerged as one of substantial
      immigration. This reflects two main forces. First, the countries of Central and
      Eastern Europe have become stepping stones on the way to the lotus lands of
      Western Europe....Second, some of the countries of Central and Eastern
      Europe...have become honeypots in their own right."

PMID- 12179818
TI  - The sociology of migration from the former Yugoslavia.

PMID- 12179819
TI  - European migration from East to West: present patterns and future directions.
AB  - "Present-day migration control is largely a social and political construction; it
      cannot explain the patterns and processes of East-West migration. Western
      anxieties have been misleading, and are used as a substitute for the fears of the
      Cold War period. In reality, the rich countries of Western Europe have largely
      been able to control their borders and define the sort of immigration they want
      to accept. Most of the migrants from Eastern Europe have come in an arranged
      form, particularly the ethnic migrants. Uncontrolled immigration is concentrated
      in those sectors of the economy where regulation is weak, and internal forces are
      operating in favour of unregistered immigration."

PMID- 12179820
TI  - Migration: the limits of governmental control.
AB  - "The first issue addressed in the present article is why it is so difficult for
      governments to intervene successfully in migration processes. Within the
      analytical framework of the article, the point is made that the variables
      addressed by governmental measures form only a small part of the relevant
      variables. Addressing these variables effectively is further hampered by the
      conflicting interests of various economic sectors and by the conflicting roles
      various administrative institutions have defined for themselves. Finally the
      article addresses the question of whether a ?root-cause' approach offers better
      prospects for the management of migration. This does not appear to be the case at
      the moment."

PMID- 12179821
TI  - The new gastarbeiter system in Germany.
AB  - "Germany's new gastarbeiter policy is evaluated in the context of a long
      tradition of labour recruitment, particularly the last period of active
      recruitment abroad (1955-1973). The policy's characteristic features (of
      permission to stay being dependent on a work permit; this being limited to a
      certain period and linked to the requirements of a specific employer) [imply]
      that the gastarbeiter regime is a low cost means of increasing flexibility in
      cases of regional and/or sectoral bottlenecks in the employment system as well as
      a way of ?exporting' problems.... The mounting employment crisis in Germany has
      prompted the German government repeatedly to take advantage of provisions to
      restrict the conventions on labour movement."

PMID- 12179822
TI  - The political discourse on quota immigration in Germany.
AB  - "Since the late 1980s many professional politicians and social interest
      associations/organisations have been arguing for the creation of an immigration
      law which would allow and organise limited and legal new immigration to Germany
      on the basis of annual or two-three year quotas.  This political discourse on
      immigration policy contains proposals which go beyond pure self-interest and aim
      to contribute to the stated goals of ?citizenship in Europe' and ?open,
      transnational citizenship'. This position is so far only held by a minority. More
      dominant are the proponents of quota immigration policy and of political asylum
      and civil refugee policies, directly or indirectly exclusionist in relation to
      ?old' and/or ?new' immigrants and refugees. This article presents the argument
      for rethinking and restructuring the notion of quota immigration rather than
      rejecting it altogether."

PMID- 12179823
TI  - Admission policy, patterns of migration and integration: the German and French
      case compared.

PMID- 12179824
TI  - Regulating ethnic immigration: the case of the Aussiedler.

PMID- 12179825
TI  - Guest worker policies for the twenty-first century.

PMID- 12179826
TI  - Bosnian refugees in the Scandinavian countries: a comparative perspective on
      immigration control in the 1990s.
AB  - "In all the Nordic countries, a change of direction in refugee policy has taken
      place in recent years, primarily for similar reasons to those in the rest of
      Western Europe. These changes have been sparked off by the situation in the
      former Yugoslavia, but should also be seen as reflecting something more.... The
      prospect of a continuing influx of refugee groups, and a corresponding strain on
      national budgets, creates a backdrop for new thinking in all countries. An
      interesting aspect of this issue in the Nordic region is that, despite being a
      fairly homogeneous area, these countries have chosen radically different points
      of departure for their approach to refugees from Bosnia-Herzegovina. The article
      identifies these different national strategies and analyses the subsequent
      tendency towards convergence of policies that has taken place along the way."

PMID- 12179827
TI  - Immigration and the modern welfare state: the case of USA and Germany.
AB  - "This article presents a comparison of the inclusion of migrants into welfare
      programmes in the USA and in Germany. In the first part of the article a brief
      overview is provided of immigration categories in both countries in order to
      demonstrate the relevance of these administrative regulations for the
      opportunities of individual migrants to participate in the welfare system. In the
      second part we elaborate in more detail on how welfare programmes have developed
      as basic mechanisms to include or exclude migrants. Our findings illustrate an
      increasing differentiation of membership statuses parallel to the expansion of
      modern welfare systems. In both the USA and Germany, the territorial principle
      and participation in the labour market are of prime importance to the access to
      social rights. In both cases all migrants may profit from contributory
      programmes."

PMID- 12179829
TI  - Goodbye Yellow Brick Road:  the spatial mobility and immobility of Britain's
      ethnic population, 1971-81.

PMID- 12179828
TI  - The Chinese in Britain.
AB  - "This research note offers a brief historical perspective on the relationship
      between Hong Kong and Britain and describes the demographic profile of the
      Chinese community in Britain...[using] information obtained from the 1991 [UK]
      Census.... The data analysis shows that the Chinese population is widely
      dispersed and increasing rapidly, and is characterised by a high child-bearing
      capacity and a low rate of unemployment."

PMID- 12179830
TI  - Immigration to Greece: a critical evaluation of Greek policy.
AB  - "In the light of the EU's interest in the movement of labour within the Union,
      the first part of this article looks at the character of Greek migrant labour
      with the aim of providing an overview of changes in the flow of migrant labour
      into Greece and of the policies adopted in relation to immigrant labour. It
      discusses the failure of the Greek government to formulate strategic measures to
      combat illegal immigration...and the limited (if any) efforts being made to aid
      the integration of Albanians. The second part of the article concentrates on [the
      experiences of] Albanian migrant labourers in Greece....[It] also assesses the
      similarities and differences in the employment positions of Albanian men and
      women in Greece and the way in which mechanisms of marginalisation differently
      affect these two categories."

PMID- 12179831
TI  - The impact of migration policy on the labour market performance of migrants: a
      comparative case study.

PMID- 12179832
TI  - The Irish in Britain:  intermarriage and fertility levels, 1971-1976.

PMID- 12179833
TI  - New Zealand:  ethnic questions in the census and other official data.

PMID- 12179834
TI  - Immigration and settlement in the Netherlands.

PMID- 12179835
TI  - IPPF/WHR service statistics for 1987.

PMID- 12179836
TI  - New clinical services in Argentina.

PMID- 12179837
TI  - Family planning in the workplace in Jamaica.

PMID- 12179838
TI  - Successful trial of "no-scalpel" vasectomy.

PMID- 12179839
TI  - BEMFAM delivers AIDS alert.

PMID- 12179840
TI  - Dismissing rumors in rural and urban areas of Honduras.

PMID- 12179841
TI  - The transition to sustainable family planning programs.

PMID- 12179842
TI  - PROFAMILIA's proven ability to bring family planning to the Dominican Republic.

PMID- 12179844
TI  - IPPF Vision 2000.

PMID- 12179843
TI  - PPFC of Canada a committed partner.

PMID- 12179845
TI  - PRO-FAMILIA -- projects for today's social realities. Puerto Rico.

PMID- 12179846
TI  - Belize -- the new IPPF / WHR member.

PMID- 12179847
TI  - The witches' district: the urbanization process.

PMID- 12179848
TI  - Family planning in Latin America's barriadas.

PMID- 12179849
TI  - New family planning center serves 60,000 Nicaraguans.

PMID- 12179850
TI  - Caribbean male: macho and insensitive?

PMID- 12179851
TI  - Are Latin American and Caribbean men irresponsible with regard to family
      planning? A surprising male view.

PMID- 12179852
TI  - Are Latin American and Caribbean men irresponsible with regard to family
      planning? An inaccurate view of Caribbean men.

PMID- 12179853
TI  - Integrating AIDS components into the region's family planning programs.

PMID- 12179854
TI  - Are Latin American and Caribbean men irresponsible with regard to family
      planning? It is the couple who gets pregnant.

PMID- 12179855
TI  - The shape of things to come.

PMID- 12179856
TI  - Omnibus Report: Europe, Middle East, Africa, East Asia and Latin America.

PMID- 12179858
TI  - Rich countries and poor countries revisited.

PMID- 12179857
TI  - Penang.

PMID- 12179860
TI  - [Demography and human ecology].

PMID- 12179859
TI  - [Migration in the framework of the single European market].

PMID- 12179862
TI  - [Theories of population and modernity: the Portuguese case].

PMID- 12179861
TI  - [Portuguese emigration trends in the twentieth century and their impact on the
      national economy].

PMID- 12179863
TI  - [Demographic aging: a proposal to consider the course of events].

PMID- 12179864
TI  - [Employment and migration in Europe: perspectives for the 1980s].

PMID- 12179866
TI  - [A regional analysis of the decline in the fertility of the population of
      Portugal (1930-1970)].

PMID- 12179865
TI  - [Demographic trends in Portugal in the period 1970-1980:  global aspects].

PMID- 12179867
TI  - [Analysis of some emigrational cycles of Portuguese population emigration].

PMID- 12179868
TI  - [On the dynamics of the Portuguese population during the period 1930-1970].

PMID- 12179869
TI  - [The replacement of generations in Portugal:  a regional analysis (1930-1975)].

PMID- 12179870
TI  - [Neo-Malthusianism in liberal propaganda].

PMID- 12179871
TI  - The epidemiology of AIDS in Africa.

PMID- 12179872
TI  - Epidemiology of AIDS in Africa--part 2.

PMID- 12179873
TI  - Depo Provera: still controversial.

PMID- 12179874
TI  - The spread of AIDS.

PMID- 12179875
TI  - Tetanus facts.

PMID- 12179876
TI  - Paucity of family planning.

PMID- 12179877
TI  - Maternal mortality: a problem whose time has come.

PMID- 12179878
TI  - 500,000 lives saved each year. ORT 10 years after.

PMID- 12179879
TI  - Critical elements of Health for All strategies: population and women's issues.

PMID- 12179880
TI  - Brazilian government pushed to action on AIDS.

PMID- 12179881
TI  - Global contraceptive use improves health.

PMID- 12179882
TI  - Poor immunization coverage--a problem of supply or demand?

PMID- 12179883
TI  - Measuring the prevalence of immunization.

PMID- 12179884
TI  - Nigeria's new population policy.

PMID- 12179885
TI  - International health and family planning.

PMID- 12179886
TI  - Some notable patterns of fertility behaviour in Africa:  the case of Kenya.
AB  - "The high rate of population growth in Africa has led to government attempts to
      encourage fertility control, but economic development does not seem to be
      following Western demographic transition theory.  Kenyan total fertility was 8.1
      children in 1979 and mean desired number of children for ever married women is
      7.2.  Key patterns of fertility contributing to these figures are high levels of
      pre- and non-marital fertility, traditional orientations to fertility, low
      prevalence of modern orientations to family size and contraception, regional and
      ethnic variations and high fertility among young urban women."  The value of
      existing theories of fertility in explaining these trends is considered.

PMID- 12179887
TI  - Labour migration and the single European market:  a synthetic and prospective
      note.
AB  - "The present paper is an attempt to analyse and forecast the following major
      issues relating to migration in Europe after 1992:  (i) the evolution and
      structure of intra-European flows in the forthcoming single European market; (ii)
      the integration, after 1992, of established immigrant communities, including
      ethnic minorities and second generation groups; (iii) future immigration from non
      EC member states.... The article explains that, in addition to policy-related
      mutations inherent in the completion of the internal market, other factors
      (demographic changes and insufficient enrolment of national graduate students in
      key disciplines) and issues (emergence of atypical groups such as second
      generation and Eastern European migrants), are due to generate new patterns and
      modified interests in European labour migration after 1992."

PMID- 12179888
TI  - The life experience and status of Chinese rural women from observation of three
      age groups.
AB  - Interview data gathered during 2 surveys in Anhui and Shejiang Provinces in 1986
      and 1987 are used to depict changes in the social status and life situation of
      rural women in China in 3 age groups, 18-36, 37-55, and 56 and over.  For the
      younger women, marriage increasingly is a result of discussion with parents, not
      arrangement, but 3rd-party introductions are increasing.  They are active in
      household and township enterprises and aspire to more education and economic
      independence.  The middle-aged group experienced war and revolution and now work
      nonstop under the responsibility system of household production, aspiring to
      university education for sons and enterprise work for daughters.  The older
      women, while supported by their sons, live a frugal existence.  In general,
      preference for sons is still prevalent and deep-seated.  At the same time, the
      bride price and costs of marriage are increasing and of widespread concern. 
      Rural socioeconomic growth is required before Confucian traditions are overcome.

PMID- 12179889
TI  - Gender, migration and social change.
AB  - "This paper provides a critical review of existing studies about how migration
      alters women's position in the course of social change....First, the conceptual
      and methodological issues that bear on the assessment of changing gender
      relations are distilled from the existing literature.  Second, for heuristic
      purposes we delineate three alternative outcomes for migrant women using the
      distribution-redistribution analytical framework....Finally, we provide a
      selective review of case studies illustrating alternative outcomes for migrant
      women in Africa and Latin America." (SUMMARY IN FRE)

PMID- 12179890
TI  - The emigration potential of Czechoslovakia, Hungary, Lithuania, Poland and
      Russia:  recent survey results.
AB  - The author reviews recent evidence concerning the emigration potential of Russia
      and Eastern Europe, using data from a 1991 survey of 4,269 respondents.  "It is
      demonstrated that the proportion of adults wishing to emigrate from each of these
      countries in February 1991 varied from a low of 2 per cent in Lithuania to a high
      of 13 per cent in Poland. Total emigration potential from the region is estimated
      to have been between 10.2 and 16.7  million....A multiple regression analysis
      indicates that age and pessimism concerning democracy are the main factors that
      were independently associated with desire to emigrate."

PMID- 12179891
TI  - Labour migration and rural transformation in Nigeria.

PMID- 12179892
TI  - Women migrants in Nigeria.

PMID- 12179893
TI  - Population growth and the demographic transition in Kenya.

PMID- 12179894
TI  - Grounding a theory of African migration in recent data on Ghana.

PMID- 12179895
TI  - Population growth, agrarian peasant economy and environmental degradation in
      Tanzania.

PMID- 12179896
TI  - The socio-psychological factors of family planning with special reference to
      Iran: a theoretical appraisal.
AB  - Iran's explosive population growth, which increases the country's population by
      about 1.9 million people annually, is causing a considerable strain on resources
      and the environment, and the coming generations will be facing a serious
      situation unless this trend is reversed. The strength of cultural values has not
      encouraged a declining population growth rate in parallel with the Iranian wave
      of modernization before and after the revolution. A special cultural revolution
      is the prerequisite for a demographic revolution. This study is placing main
      emphasis on the social and psychological factors involved in family planning. The
      general findings of surveys conducted so far demonstrate that few people know
      anything about family planning and methods of contraception. Social, cultural,
      and religious institutions seem to inhibit the expansion of family planning.
      Moreover, the lack of economic and social security promotes a large family size
      and prevents contraceptive use. However, social change in Iranian society will
      eventually be brought about by urbanization, industrialization, and education,
      and the ensuing modernization of values is expected to increase the use of
      contraceptives and lead to changes in the associated social and cultural
      institutions.

PMID- 12179897
TI  - Racism, migration and the state in Western Europe:  a case for comparative
      analysis.
AB  - This paper offers a framework for the comparative analysis of international
      migration into Western Europe since 1945.  It identifies "the migration of four
      analytically distinct categories of person which highlights the role of the state
      in the reproduction of the imagined community of nations. That role is carried
      out in the context of a more general process of the regulation of scarcity, in
      the course of which people are simultaneously included in and excluded from the
      hierarcy of economic, political and ideological positions in the nation-state. 
      Of special interest is the content of the processes of signification and
      categorisation that are generated in the inclusionary and exclusionary processes.
      The countries selected for analysis are France, the Netherlands and Britain."

PMID- 12179898
TI  - The socio-cultural context of high fertility among Igbo women.

PMID- 12179899
TI  - From physiology to feminism. Reconfiguring body, gender and expertise in natural
      fertility control.

PMID- 12179900
TI  - Towards a better South Africa, but ... biggest problem often overlooked.

PMID- 12179901
TI  - Poor, powerless and pregnant. Empowering women will benefit all.

PMID- 12179902
TI  - Literacy. A corner stone for development.

PMID- 12179903
TI  - Solving the imminent survival crisis: church can make a valuable contribution.

PMID- 12179904
TI  - Rapid population growth: drastic action needed to curb numbers.

PMID- 12179906
TI  - Population Development Programme. Reduction of fertility rate a major goal.

PMID- 12179905
TI  - The role of the business community: investing in human potential.

PMID- 12179907
TI  - South Africa's position. Present generation can still prevent a crisis.

PMID- 12179909
TI  - A network to "eradicate" poor-quality vaccines.

PMID- 12179908
TI  - Hep B: more haves, but too many have-nots.

PMID- 12179910
TI  - From the Expanded Programme on Immunization (EPI) database: diphteria.

PMID- 12179911
TI  - Immunization news.

PMID- 12179912
TI  - Polio roundup. Grappling with the "problem" areas.

PMID- 12179913
TI  - Africa nears end of polio.

PMID- 12179914
TI  - View from the chair -- on tuberculosis vaccines.

PMID- 12179915
TI  - Vaccine supply and quality news.

PMID- 12179916
TI  - Upcoming vaccines should fill gaps in meningitis control.

PMID- 12179917
TI  - Deaths, severe reactions after DTP not due to vaccine, says study team. Adverse
      reactions in Kazakhstan.

PMID- 12179918
TI  - Vaccine researchers rise to the challenge of resurgent TB.

PMID- 12179919
TI  - Vaccine vial monitors take guesswork out of immunization.

PMID- 12179920
TI  - The diphtheria epidemic in Eastern Europe (still going strong).

PMID- 12179921
TI  - Polio -- the final ascent.

PMID- 12179922
TI  - Polio eradication still on target for 2000.

PMID- 12179923
TI  - Wood energy: the role of women's unvalued labor.

PMID- 12179924
TI  - Achieving sustainable agriculture through recognizing gender roles: some salient
      points.

PMID- 12179925
TI  - Gender-related impacts of improved agricultural technologies: identification of
      indicators from a case study.

PMID- 12179926
TI  - Food Security and Women's Access to Natural Resources workshop; a brief report.

PMID- 12179927
TI  - The GenDev Curriculum Development Workshop.

PMID- 12179928
TI  - Globalization of the economy and women's work in a sustainable society.

PMID- 12179929
TI  - Technology transfer for women entrepreneurs: issues for consideration.

PMID- 12179930
TI  - Hmong women, opium cultivation and livestock production in Lao PDR.

PMID- 12179931
TI  - Women's independent access to productive resources: fish ponds in the Oxbow Lakes
      Project, Bangladesh.

PMID- 12179932
TI  - Rural and indigenous women speak out on the impact of globalization.

PMID- 12179933
TI  - Women's roundtable discussion on the economic, social and political impacts of
      the Southeast Asian financial crisis.

PMID- 12179934
TI  - Can markets alter gender relations?

PMID- 12179935
TI  - Making women's voices heard: technological change and women's employment in
      Malaysia.

PMID- 12179936
TI  - Globalization, technological changes and the search for a new paradigm for
      women's work.

PMID- 12179937
TI  - Gender, technology change and globalization: the case of China.

PMID- 12179938
TI  - Engendering development theory from the standpoint of women.

PMID- 12179939
TI  - Gender and the environment: recent initiatives to improve sustainable development
      policy, planning and practice.

PMID- 12179940
TI  - Gender training in aquaculture in northern Vietnam. A report.

PMID- 12179942
TI  - Women's labor in Bangladesh and Sri Lanka: the trade-off with technology.

PMID- 12179941
TI  - Transitional economy, technological change and women's employment: the case of
      Vietnam.

PMID- 12179943
TI  - Rethinking gender planning: a critical discussion of the use of the concept of
      gender.

PMID- 12179944
TI  - Women and ethnic cleansing: a history of Partition in India and Pakistan.

PMID- 12179945
TI  - From anti-arrack to total prohibition: the women's movement in Andhra Pradesh,
      India.

PMID- 12179946
TI  - Post-Fordist technology and the changing patterns of women's employment in the
      Third World.
AB  - Literate but unskilled--and largely female--labor has thus far fueled the
      tremendous increase in manufactured exports of garments and microelectronic
      products from the Third World to the industrially advanced economies of the
      North.  The future growth of these sectors, however, may require literate and
      skilled workers--a category in which women are woefully under-represented,
      especially in the Third World.  In the case of the garment industry, defensive
      innovation in the industrially advanced countries, including automation and
      flexible management, has initiated a relocation of jobs to these countries or to
      offshore locations geographically close to their markets.  Automated garment
      production in these countries requires fewer but computer-literate workers.  In
      the case of microelectronics, development policies of East Asian countries and
      the competitive pressures on start-up companies in the North have led to an
      increased demand for computer-literate, skilled technicians over the unskilled
      and overwhelmingly female workforce of manual-assembly workers.  Women's
      continued employment and advancement in these industries globally will depend
      upon their acquisition of new technical skills.  The ratification by the 1995
      international women's conference at Beijing of the demand for better access to
      education and skills training for women, especially in the Third World, is a step
      in the right direction.

PMID- 12179947
TI  - Gender relations and housing: a cross-community analysis.
AB  - Housing is not only a technological product, it is also a product of culture and
      gender relations.  Gender differentiation in the means adopted to meet basic
      needs, access to religious spaces, social interaction, ownership and inheritance
      systems is reflected in built technology, affecting housing elements like the
      quality and size of space.  And just as gender differentiation affects the
      structure of the house, so also the structure of the house reveals existing
      hierarchies and perpetuates different access to opportunities.  It adds to
      difficulties in sharing household responsibility and comes in the way of
      efficiently running the household, affecting women's health and reinforcing
      existing gender relations.  This paper studies gender relations as they affect
      housing in the case of the Newar community of Khokana village in Nepal.  To
      highlight key points, illustrative examples are taken from a Karen and an Isan
      village in Thailand.

PMID- 12179948
TI  - Women's perspectives on public policy in India: a half-century of incomplete or
      lost agenda?
AB  - 52 years is not a small period for initiating progress.  The promises enshrined
      in the Indian Constitution and the vision of women's full emancipation advanced
      during the nationalist struggle have alas not merely receded, but there is every
      danger that the lost momentum may not be made up unless once again the authors
      gear ourselves to intervene more forcefully in the polity and public policy. 
      What we find despite tall pronouncements and a great deal of rhetoric and
      sentiment, is that the reality of public policy that emerges is full of
      ambiguities, ambivalences and contradictions, often taking away with the left
      hand what the right hand gives.  Women's recommendations towards a radical
      movement for promoting gender equality in free India got jettisoned.  The cost to
      women of this neglect is documented by plenty of data.  In spheres such as
      employment, education, population, health, family laws, environment, and criminal
      justice, the response of the state has often been either detrimental to women or
      merely helped maintain the status quo.  In many spheres, while women's
      interventions have been substantial, these were like a finger in the dyke, unable
      to reverse major policy directions.

PMID- 12179949
TI  - Ageism and sexism at work: the middle-aged women of Hong Kong.
AB  - Employment discrimination against middle-aged women has recently captured public
      attention in Hong Kong.  One reason is the economic slowdown and increasing
      unemployment since the 1993-94 and the 1997-to date economic downturns.  This
      paper looks at sex and age discrimination against middle-aged women in colonial
      Hong Kong where they faced such problems as low labor force participation,
      occupational and industrial segregation and wage differentials, which in turn
      left them vulnerable to unemployment and poverty.  Rampant age and sex
      discrimination in the workplace is due to a number of factors: traditional values
      and cultural devaluation of women's work and need for education, economic
      restructuring and labor importation, a legal vacuum, inefficient retraining
      policy, and the weak position of women in the labor movement.  The postcolonial
      government under Tung Chee Hwa is heavily influenced by business interests. 
      Women in the age group of 30-39 and above are hardest hit.  They are not targeted
      as special groups of trainees who require special assistance.  Given the limited
      concern for gender development on the part of the new government, the prospect
      for women workers does not look good.

PMID- 12179950
TI  - Counting women's work in the agricultural census of Nepal: a report.
AB  - Like many national statistical surveys, the Agricultural Census of Nepal does not
      reflect the actual contribution of women's work in agriculture.  Inadequacies in
      conceptualization, definition of terms and data gathering methods result in
      undervaluation and underrepresentation of women's work.  This study of 124 Newar
      households in the Lubhu Village Development Committee, Kathmandu Valley, provides
      a statistical representation of women's roles in agricultural operations and
      household activities by assessing the actual extent of their work.  After
      analyzing the gender division of labor, the study concludes that women's work in
      agriculture and household activities is significantly higher than men's work.

PMID- 12179951
TI  - Women in science, engineering and technology (SET): a report on the Indonesian
      experience.
AB  - This paper presents the preliminary results of a study by the Gender Working
      Group, Indonesian Institute of Sciences, on women's contribution to, and benefits
      to women from, science, engineering and technology (SET), specifically the
      benefits accruing to disadvantaged women in urban and rural areas in Indonesia.
      Previous studies on the participation of women in SET have shown the under
      representation of women in all SET activities, including decision-making and
      advisory positions.  However, some studies have shown that if gender perspectives
      are included in the design and implementation of development activities,
      disadvantaged women in urban and rural areas could greatly benefit from SET in
      development projects.  The two case studies in North Sulawesi and Central Lombok
      provinces show that the projects have enabled the expansion of employment
      opportunities for women and thus increased their technical skills and income.  In
      addition, the projects have also contributed to enhancing women's self
      confidence, self-reliance and communication skills.

PMID- 12179952
TI  - Gender, culture, and architecture in Ahmedabad and Berlin.
AB  - Spatial and social processes are inextricably linked.  Hence gender relations as
      an inherent part of social relations get built into the spatial forms of any
      society.  Spatial segregation by sex was a mark of traditional societies.  This
      has diminished somewhat in contemporary societies due to various factors, perhaps
      the most important being the entry of women into the public sphere and their
      participation in income-earning activities.  This paper looks at traditional,
      modern and postmodern housing in two cities--Ahmedabad and Berlin--through the
      lens of gender and culture.  While there have been changes in housing over time,
      these changes have not been in proportion with the changes in gender relations in
      society which, in turn, have not kept pace with the way women's needs and
      priorities have changed.  Housing must necessarily reflect the current needs of a
      society, and that entails reflecting the needs of both women and men equally.

PMID- 12179953
TI  - Is cyberspace a new communicative space for women?

PMID- 12179954
TI  - Critical velocity and time spent at a high level of VO2 for short intermittent
      runs at supramaximal velocities.
AB  - This study was designed to determine the intermittent critical velocity, the time
      spent at maximal oxygen uptake (VO2max) and the time spent above 90% of VO2max
      for short intermittent runs of 15 s at supramaximal velocities, alternating with
      15 s of passive recovery. Nine male subjects performed 5 field-tests to
      exhaustion (tlim): 4 intermittent runs at 110%, 120%, 130% and 140% of maximal
      aerobic speed (MAS) and 1 continuous run at 100% of MAS. Results have shown the
      mean intermittent critical velocity (4.82 +/- 0.41 m.s-1) was not significantly
      different from MAS (4.63 +/- 0.37 m.s-1). Intermittent runs at 110% and 120% of
      MAS and the continuous run at 100% of MAS lead all subjects to reach VO2max.
      However, intermittent runs at 120% of MAS (202 +/- 66 s) allowed subjects to
      spend a significantly longer time at VO2max (p < .05) than intermittent runs at
      110% (116 +/- 42 s), 130% (50 +/- 47 s), 140% (48 +/- 59 s) of MAS and continuous
      run at 100% of MAS (120 +/- 42 s). The time spent between 90 and 100% of VO2max
      was significantly longer (p < .05) for intermittent runs at 110% (383 +/- 180 s)
      and for 120% (323 +/- 272 s) of MAS than for intermittent runs at 130% (135 +/-
      133 s), 140% of MAS (77 +/- 96 s) and for continuous run at 100% of MAS (217 +/-
      114 s). Consequently, this kind of intermittent exercise with intensities from
      intermittent critical velocity to 120% of MAS could be introduced in a training
      program when the purpose is to increase VO2max.

PMID- 12179955
TI  - Reliability of concentric ankle dorsiflexion fatigue testing.
AB  - The purpose of this study was to determine the reliability of an isokinetic test
      for ankle dorsiflexion fatigue on a Biodex dynamometer. Young (21 to 32 years),
      recreationally active men (n = 10) and women (n = 10) performed 50 concentric (60
      degrees.s-1) dorsiflexion contractions, on two different occasions. Total work
      (TW), losses in work (work fatigue; WF), as well as relative losses in peak
      toruqe, an example being "3-3" which compared the first three to last three
      repetitions, were measured. The intra-class correlation coefficients (ICC2.1) and
      coefficients of variation (CV), as well as the Bland-Altman plots and analyses
      showed that the variables using peak torque and TW were more reliable than WF,
      with WF having a CV of 11.3% and the best peak torque variable, 3-3, having a CV
      of 5.6%. In conclusion, ankle dorsiflexion fatigue can be reliably assessed on a
      Biodex dynamometer.

PMID- 12179956
TI  - Exercise- and insulin-stimulated muscle glucose transport: distinct mechanisms of
      regulation.
AB  - In mammals, skeletal muscle is the primary target for the stimulation of glucose
      transport by a variety of activators. These include the hormone insulin and
      stimuli which increase energy demand such as exercise, hypoxia, and challenges to
      the oxidative chain. While it is known that both stimuli rapidly elevate glucose
      uptake into muscle by signalling the translocation of glucose transporters from
      intracellular stores to the plasma membrane, there are numerous contrasts between
      energy stressors and insulin in their mechanisms of glucose transport activation.
      Exercise and insulin recruit distinct intracellular pools of glucose transporters
      in skeletal muscle and the maximal effects of contraction and insulin are
      additive. Activation of phosphatidylinositol 3-kinase (PI3-K) is utilized by
      insulin to induce glucose transporter translocation, but does not participate in
      the responses to exercise or hypoxia. These findings suggest that energy
      stressors utilize different mechanisms from insulin to increase glucose influx;
      however, how these factors elicit their response is not clear. This review will
      summarize our current knowledge of these alternative pathways of glucose
      transport regulation. Emphasis is placed on the use of the mitochondrial
      uncoupler dinitrophenol to investigate mediators of this alternative signalling
      pathway in L6 muscle cells, a line used to characterize physiological responses
      in muscle such as glucose transport.

PMID- 12179957
TI  - New perspectives on the storage and organization of muscle glycogen.
AB  - Due to its large mass, skeletal muscle contains the largest depot of stored
      carbohydrate in the body in the form of muscle glycogen. Readily visualized by
      the electron microscope, glycogen granules appear as bead-like structures
      localized to specific subcellular locales. Each glycogen granule is a functional
      unit, not only containing carbohydrate, but also enzymes and other proteins
      needed for its metabolism. These proteins are not static, but rather associate
      and dissociate depending on the carbohydrate balance in the muscle. This review
      examines glycogen-associated proteins, their interactions, and roles in
      regulating glycogen metabolism. While certain enzymes such as glycogen synthase
      and glycogen phosphorylase have been extensively studied, other proteins such as
      the glycogen initiating and targeting proteins are just beginning to be
      understood. Two metabolically distinct forms of glycogen, pro- and marcoglycogen
      have been identified that vary in their carbohydrate complement per molecule and
      have different sensitivities to glycogen synthesis and degradation. Glycogen
      regulation takes place not only by allosteric regulation of enzymes, but also due
      to other factors such as subcellular location, granule size, and association with
      various glycogen-related proteins.

PMID- 12179958
TI  - Biotic interactions. Web alert.

PMID- 12179959
TI  - The dialogue between viruses and hosts in compatible interactions.
AB  - Understanding the biological principles behind virus-induced symptom expression
      in plants remains a longstanding challenge. By dissecting the compatible host
      virus relationship temporally and genetically, we have begun to map out the
      relationships of its component parts. The picture that emerges is one in which
      host gene expression and physiology are under tight temporal control during
      infection.

PMID- 12179960
TI  - Quorum sensing in plant-associated bacteria.
AB  - N-acyl homoserine lactone (AHL)-mediated quorum sensing by bacteria regulates
      traits that are involved in symbiotic, pathogenic and surface-associated
      relationships between microbial populations and their plant hosts. Recent
      advances demonstrate deviations from the classic LuxR/LuxI paradigm, which was
      first developed in Vibrio. For example, LuxR homologs can repress as well as
      activate gene expression, and non-AHL signals and signal mimics can affect the
      expression of genes that are controlled by quorum sensing. Many bacteria utilize
      multiple quorum-sensing systems, and these may be modulated via post
      transcriptional and other global regulatory mechanisms. Microbes inhabiting plant
      surfaces also produce and respond to a diverse mixture of AHL signals. The
      production of AHL mimics by plants and the identification of AHL degradative
      pathways suggest that bacteria and plants utilize this method of bacterial
      communication as a key control point for influencing the outcome of their
      interactions.

PMID- 12179961
TI  - The genomics parade of defense responses: to infinity and beyond.
AB  - Genomic-scale methods, such as cDNA microarrays, cDNA-AFLP analyses and
      proteomics are revolutionizing the study of plant-pathogen interactions, and are
      revealing a complex web of signaling cascades involved in plant defense
      responses. Recent studies have shown that responses to pathogens and
      environmental stresses are linked, suggesting that genes previously identified as
      stress-responsive may also play an active role in plant defense. As a result of
      proteomic analysis, proteins involved in early defense signaling are coming to
      light.

PMID- 12179962
TI  - Polygalacturonase-inhibiting proteins in defense against phytopathogenic fungi.
AB  - Polygalacturonase-inhibiting proteins (PGIPs) are ubiquitous plant cell wall
      proteins that are directed against fungal polygalacturonases (PGs), which are
      important pathogenicity factors. The inhibiting activity of PGIPs directly
      reduces the aggressive potential of PGs. In addition, it causes PGs to form more
      long-chain oligogalacturonides that are able to induce defense responses, thereby
      indirectly contributing to the plant defense. Recent evidence demonstrates that
      PGIPs are efficient defense proteins and limit fungal invasion. PGIPs and the
      products of many plant resistance genes share a leucine-rich repeat (LRR)
      structure, which provides specific recognition of pathogen-derived molecules. The
      high level of polymorphism of both PGIPs and polygalacturonases is an invaluable
      tool for deciphering the structure, function and evolution of plant LRR proteins
      and their ligands. Furthermore, information about PGIP structure and evolution
      paves the way to the development of efficient strategies for crop protection.

PMID- 12179963
TI  - Constitutive plant toxins and their role in defense against herbivores and
      pathogens.
AB  - Most recent investigations have focused on induced, rather than constitutive,
      plant defenses. Yet significant research has helped to illuminate some of the
      principal characteristics of constitutive defenses, including mechanisms of
      action and synergistic effects, as well as strategies used by herbivores and
      pathogens to circumvent them.

PMID- 12179964
TI  - Biotic interactions of marine algae.
AB  - Marine algae encompass lineages that diverged about one billion years ago. Recent
      results suggest that they feature natural immunity traits that are conserved, as
      well as others that appear to be phylum- or environment-specific. In particular,
      marine plants resemble terrestrial plants and animals in their basic mechanisms
      for pathogen recognition and signaling, suggesting that these essential cell
      functions arose in the sea. Specific traits are based on the synthesis of unique
      secondary defense metabolites, often making use of the variety of halides found
      in the sea.

PMID- 12179965
TI  - Innate immunity in plants and animals: emerging parallels between the recognition
      of general elicitors and pathogen-associated molecular patterns.
AB  - Recent findings have highlighted remarkable similarities in the innate pathogen
      defense systems of plants, animals and insects. Pathogen-associated molecular
      patterns (PAMP) that are similar to those activating innate immune responses in
      animals have been shown to mediate the activation of plant defense. Moreover,
      recognition complexes that are structurally related to animal PAMP receptors are
      now being discovered in plants, suggesting a common evolutionary origin of
      pathogen defense systems in higher eukaryotes.

PMID- 12179966
TI  - Cross talk between signaling pathways in pathogen defense.
AB  - Plant defense in response to microbial attack is regulated through a complex
      network of signaling pathways that involve three signaling molecules: salicylic
      acid (SA), jasmonic acid (JA) and ethylene. The SA and JA signaling pathways are
      mutually antagonistic. This regulatory cross talk may have evolved to allow
      plants to fine-tune the induction of their defenses in response to different
      plant pathogens.

PMID- 12179967
TI  - Phospholipid signalling in plant defence.
AB  - Phospholipid-derived molecules are emerging as novel second messengers in plant
      defence signalling. Recent research has begun to reveal the signals produced by
      the enzymes phospholipase C, phospholipase D and phospholipase A2 and their
      putative downstream targets. These include the activation of a MAP kinase cascade
      and triggering of an oxidative burst by phosphatidic acid; the regulation of ion
      channels and proton pumps by lysophospholipids and free fatty acids; and the
      conversion of free fatty acids into bioactive octadecanoids such as jasmonic
      acid.

PMID- 12179968
TI  - Yield penalties of disease resistance in crops.
AB  - Recently, there have been rapid developments in understanding the costs of
      disease and pest resistance in model plants and their ecological relevance in
      wild plants. In crop plants, however, much (although not all) of our current
      understanding of costs of resistance must be inferred from research on model
      species. To determine the true costs of resistance in crops and the likely
      benefit of resistance genes in new cultivars, however, other aspects of the
      plant's phenotype must be studied alongside resistance.

PMID- 12179969
TI  - Ecological costs of induced resistance.
AB  - There has been rapid progress in detecting the genetic or allocation costs of
      induced resistance. In addition to these 'internal' costs, ecological costs may
      result from external mechanisms, that is, from the detrimental effects of
      resistance on the plant's interactions with its environment. All evolutionarily
      relevant costs affect a plant's ability to perform under natural conditions. The
      conceptual separation of different forms of resistance costs simplifies the study
      of mechanisms by which these costs arise. Yet, integrative measures of fitness
      must be applied under natural conditions so that researchers can fully understand
      the costs and benefits of induced resistance.

PMID- 12179970
TI  - Volatile signaling in plant-plant-herbivore interactions: what is real?
AB  - Plants release volatiles after herbivore attack in a highly regulated fashion.
      These compounds attract natural enemies and function as indirect defenses.
      Whether neighboring plants 'eavesdrop' on these volatile signals and tailor their
      defenses accordingly remains controversial. Recent laboratory studies have
      identified transcriptional changes that occur in plants in response to certain
      volatiles. These changes occur under conditions that enhance the probability of
      signal perception and response. Field studies have demonstrated repeatable
      increases in the herbivore resistance of plants growing downwind of damaged
      plants.

PMID- 12179971
TI  - Ectomycorrhiza: gene expression, metabolism and the wood-wide web.
AB  - In the ectomycorrhizal symbiosis between fungi and trees, the fungus completely
      ensheaths the tree roots and takes over water and mineral nutrient supply, while
      the plant supplies photosynthate. Recent work has focussed on gene expression in
      the two partners, on the effects of global change and nitrogen deposition rate on
      the symbiosis, and on the role of mycorrhizal fungi in connecting individual
      plants to form a 'wood-wide web'.

PMID- 12179972
TI  - Enantioseparation of chiral sulfoxides and sulfinate esters by capillary
      electrophoresis.
AB  - Forty-one chiral sulfoxides and sulfinate esters were separated using sulfated
      beta-cyclodextrin and carboxymethyl beta-cyclodextrin as chiral selectors.
      Binding constants of some analytes to both chiral selectors were measured in
      order to examine and help explain the observed migration behavior and
      enantioselectivity trends. Overall, sulfated beta-cyclodextrin separated a
      greater number of compounds, and had better separating capabilities than did
      carboxymethyl beta-cyclodextrin for these analytes. This was true even though all
      of the analytes showed much stronger binding to carboxymethyl beta-cyclodextrin
      than to sulfated beta-cyclodextrin. General procedures to optimize the
      separation, by varying pH, selector concentration, and organic modifier
      concentration were examined and discussed. Chiral selector concentration had the
      greatest effect on enantioseparation, with higher concentrations of selector
      giving better peak-to-peak separations. Organic modifier had an adverse affect on
      resolution, with increasing amounts giving lower mobility differences. Lastly, pH
      had only a minimal effect on separation.

PMID- 12179973
TI  - Determination of the cardiolipin content of individual mitochondria by capillary
      electrophoresis with laser-induced fluorescence detection.
AB  - We report the application of capillary electrophoresis (CE) with postcolumn laser
      induced fluorescence (LIF) detection to measure the cardiolipin content of
      individual mitochondria from cultured NS1 cells. Mitochondria were isolated by
      differential centrifugation and stained with the fluorescent dye 10-N-nonyl
      acridine orange which stoichiometrically binds to cardiolipin in a 1:1 or 2:1
      ratio depending on the dye concentration. The green fluorescence resulting from
      the 1:1 complex was chosen for analysis because it is substantially more intense
      than the red fluorescence resulting from the 2:1 complex. Two dye concentrations
      that resulted in maximal and submaximal formation of the 1:1 10-N-nonyl acridine
      orange-cardiolipin complex were identified by spectrofluorometry. Individual
      mitochondria stained with both dye concentrations were separated and detected by
      CE with LIF detection. The data from mitochondria dosed with the lower dye
      concentration, where it is assumed that all the dye added to the mitochondrial
      sample was bound to cardiolipin, were used to derive a sensitivity factor
      relating fluorescence intensity of a mitochondrial event to its cardiolipin
      content. Using this factor, the cardiolipin contents of individual mitochondria
      stained with the higher dye concentration were determined, and ranged from 1.2 to
      920 amol, with a median value of 4 amol. These results suggest a new strategy for
      estimating the organellar content of compounds that can be fluorescently tagged.

PMID- 12179974
TI  - Separation and detection of angiotensin peptides by Cu(II) complexation and
      capillary electrophoresis with UV and electrochemical detection.
AB  - The use of capillary electrophoresis (CE) with on-capillary Cu(II) complexation
      for the determination of angiotensin and its metabolites is described. The
      resulting copper-peptide complexes can be detected using either UV or
      electrochemical (EC) detection. Optimal reaction and separation conditions for
      the angiotensin peptides were first determined using CE with UV detection. With
      UV detection, the limit of detection (signal-to noise ratio S/N = 3) for native
      angiotensin II was 18 microM, while the limit of detection (LOD) obtained for the
      copper-angiotensin II complex is 2 microM. CE with EC detection was then
      evaluated, yielding significantly lower LODs--2 microM for native angiotensin II
      and 200 nM for the copper-angiotensin II complex. The addition of copper to the
      run buffer improved the separation and sensitivity for both CE-UV and CE-EC
      detection. The method was demonstrated by monitoring the conversion of
      angiotensin I to angiotensin II in plasma via angiotensin-converting enzyme (ACE)
      and subsequent inhibition of ACE by captopril.

PMID- 12179975
TI  - Proteinase assay by capillary electrophoresis employing fluorescence-quenched
      protein-dye conjugates.
AB  - Determination of proteinases--enzymes that catalyze the hydrolysis of peptide
      bonds--is often difficult due to the presence of interferences in complex
      biological media and limited sample size. Capillary electrophoresis (CE), with
      laser-induced fluorescence (LIF) can serve as a useful tool for such
      determinations. LIF detection offers the advantages of increased sensitivity and
      increased selectivity. However, direct LIF detection requires the proteinase
      analyte to be fluorescently derivatized prior to analysis. A viable alternative
      is offered by the present work, in which protein substrates are first labeled
      with BODIPY dye, a relatively pH-insensitive, high-fluorescence quantum yield
      dye. Upon binding of some 4-10 molecules of dye to a single protein, the dye is
      effectively fluorescence-quenched. Digestion of the BODIPY--labeled and quenched
      protein by an unlabeled enzyme yields smaller peptide fragments in which the
      fluorescence of associated BODIPY tags is restored. We will present how the
      fragmentation pattern of BODIPY-labeled casein changes as a function of
      incubation time with trypsin, as well as the effect of varying concentrations of
      trypsin on the BODIPY-casein digest.

PMID- 12179977
TI  - Separation of Trp-Arg and Arg-Trp using G-quartet-forming DNA oligonucleotides in
      open-tubular capillary electrochromatography.
AB  - DNA oligonucleotides that form intramolecular G-quartet structures were
      investigated as stationary phase reagents for separation of mixtures of the
      isomeric dipeptides Trp-Arg and Arg-Trp in open-tubular capillary
      electrochromatography (OTCEC). The oligonucleotides included a thrombin-binding
      aptamer that forms a biplanar G-quartet structure and an oligonucleotide that
      forms a 4-plane G-quartet structure. Fluorescence, circular dichroism and UV
      visible absorbance spectroscopies were used in batch solution studies to indicate
      interactions between the dipeptides and the biplanar G-quartet structure. Results
      for OTCEC separations were compared with results obtained for capillary zone
      electrophoresis separations on a bare capillary. Temperature studies suggest that
      resolution is improved when the G-quartet structure is partially destabilized,
      but control experiments in which potassium chloride was not included in the
      mobile phase indicate that the G-quartet structure nevertheless plays a role in
      the separations.

PMID- 12179976
TI  - Proteome analysis of camptothecin-treated cortical neurons using isotope-coded
      affinity tags.
AB  - Isotope-coded affinity tags (ICATs) were employed to identify and quantitate
      changes in protein expression between control and camptothecin-treated mouse
      cortical neurons. Proteins extracted from control cortical neurons and those
      treated with camptothecin were labeled with the light and heavy isotopic versions
      of the ICAT reagents, respectively. ICAT-labeled samples were combined,
      proteolytically digested, and the derivatized peptides isolated using immobilized
      avidin chromatography. The peptides thus isolated were analyzed by reversed-phase
      liquid chromatography coupled directly to either a conventional ion-trap mass
      spectrometer (IT-MS) or a Fourier transform ion cyclotron resonance mass
      spectrometer (FTICR). While a majority of the peptide identifications were
      accomplished using IT-MS, FTICR was used to quantitate the relative abundances of
      the ICAT-labeled peptides taking advantage of its high resolution, sensitivity,
      and duty cycle. By using this combination of MS technologies we have thus far
      identified and quantified the expression of greater than 125 proteins from
      control and camptothecin-treated mouse cortical neurons. While proteins from most
      functional classes of proteins were identified, a particularly large percentage
      of the enzymes involved in glycolysis and the tricarboxylic acid cycle were
      observed.

PMID- 12179978
TI  - Element of a validation method for MU-B3 monoclonal antibody using an imaging
      capillary isoelectric focusing system.
AB  - This paper presents an imaging capillary isoelectric focusing (CIEF) assay for
      the determination of the identity, stability, and isoform distribution of a
      murine monoclonal antibody (MU-B3). The experiments were conducted using a
      Convergent Bioscience iCE280 instrument. The optimum carrier ampholyte
      composition that gave the best peak separation was found to be 25% Pharmalyte pH
      3-10 and 75% Pharmalyte pH 5-8. The antibody gave a highly reproducible CIEF
      profile with three major peaks having average isoelectric point (pI) values of
      6.83, 6.99, and 7.11. Intraday and interday reproducibility of pI values was
      found to be within RSD of 0.5%. The CIEF profile was also the same, with an
      alternate column cartridge and alternate batches of methyl cellulose. A plot of
      peak areas versus MU-B3 concentration was linear (R2 = 0.995) up to a
      concentration of 0.5 mg/mL in the sample solution. Peak area measurements were
      reproducible to within 7% RSD. The CIEF profiles of two other antibodies were
      distinctly different from the profile of MU-B3, showing that the assay is
      specific. After a sample of MU-B3 was subjected to heat stress by exposure to
      heat at 55 degrees C for 4 h, its CIEF profile was altered with extra peaks
      appearing at lower pI values, indicating that the assay could be used to monitor
      stability. The result of the heat stress experiment was also confirmed with a
      parallel slab-gel IEF analysis of the antibody sample before and after
      application of the heat stress. The results of this work suggest that imaging
      CIEF can be used for product testing under a quality control environment. The
      assay can be used for pI profiling of proteins and for monitoring structural
      changes (deamidation, glycosylation, etc.) during the manufacturing process and
      upon storage.

PMID- 12179979
TI  - Transient pseudo-isotachophoresis for sample concentration in capillary
      electrophoresis.
AB  - We show that many water miscible organic solvents such as acetonitrile, acetone
      and small alcohols can function as a terminating ion in transient
      isotachophoresis, which leads to sample concentration on the capillary. It is
      suggested that this method could be termed transient "pseudo-isotachophoresis"
      (pseudo-ITP). Because of their low conductivity, these water miscible organic
      solvents provide the high field strength necessary for band sharpening similar to
      that provided by the terminating ion. Salts, when present in such samples act
      briefly as leading ions, migrating rapidly in the organic solvent until they are
      slowed at the interface of the separation buffer. When the organic solvents are
      added to the sample, both the migrations as well as the stacking of the analytes
      are affected by the concentration of salts (leading ions) in the sample, similar
      to that observed in isotachophoresis. Our results show that this type of stacking
      offers good reproducibility and reliability for practical analysis. In practice,
      pseudo-ITP stacking is much easier to perform compared to that of true ITP with
      several added practical advantages as discussed.

PMID- 12179980
TI  - Effect of class I and II organic modifiers on retention and selectivity in
      vesicle electrokinetic chromatography.
AB  - Vesicles are large aggregates of surfactant monomers consisting of a spherical
      bilayer surrounding an internal cavity of solvent. The bilayer structure allows
      vesicles to be attractive models for the study of various transmembrane and
      binding processes. The use of thermodynamically stable vesicles (TSV) formed from
      oppositely charged surfactants for use as a pseudostationary phase in
      electrokinetic chromatography (EKC) was first accomplished using
      dodecyltrimethylammonium bromide and sodium dodecyl sulfate (DTAB/SDS).
      Surfactant vesicles have demonstrated enhanced separation characteristics
      compared to conventional micelles in EKC, although only investigated in aqueous
      media. Organic modifiers have been widely studied and used in EKC to enhance
      separation conditions. In this study, vesicles formed from cetyltrimethylammonium
      bromide and sodium octyl sulfate (CTAB/SOS) were investigated in the presence of
      "class I and II" organic modifiers. Electrophoretic and chromatographic
      parameters were examined as well as linear solvation energy relationship analysis
      (LSER) to characterize the effects of the modifiers on retention and selectivity
      in EKC. LSER analysis is a useful way to quantitatively investigate
      solute/solvent interactions responsible for retention and selectivity.

PMID- 12179981
TI  - Stacking for nonaqueous capillary electrophoresis.
AB  - Nonaqueous capillary electrophoresis (NACE) is a useful mode in CE for separation
      and quantification of hydrophobic compounds. However, because of the low
      conductivity of most of the organic solutions, stacking is not used often in this
      technique and the sample volume is very limited. As a result of the small sample
      volume, the detection limits are poor. Furthermore, NACE is affected greatly by
      the presence of salts in the sample. Here, we show that transient
      isotachophoresis (t-ITP) can be used easily in this type of electrophoresis to
      enhance the detection limits and also to reverse the deleterious effects of salts
      in the sample. Several factors, which affect the stacking in this type of
      electrophoresis, are described. For example, the presence of salts in the organic
      solvent, type of sample introduction, and the solvent for the terminating ion
      were all found to have profound effects on the degree of concentration.
      Furthermore, the separation time can be shortened by t-ITP.

PMID- 12179982
TI  - Amplification of small analytes in polymer solution by capillary electrophoresis.
AB  - We report concentration methods for the analysis of small solutes by capillary
      electrophoresis in conjunction with laser-induced native fluorescence using a
      Nd:YAG laser. After injecting samples, poly(ethylene oxide) (PEO) in the anode
      reservoir entered a capillary filled with Tris-borate buffer. When migrating in
      PEO solution, the analytes slowed down and stacked at the interface between the
      sample zone and PEO solution. As a result, the limits of detection (LODs) down to
      8 pM for 2-naphthalenesulfonic acid and 70 pM for L-tryptophan have been achieved
      when injecting at 30 cm height for 120 s and 230 s, respectively. Such low LODs
      are partially due to the effects of NaCl in the samples and PEO on the
      fluorescence characteristics of the analytes. In addition, the concentrations of
      NaCl and PEO have great impacts on the migration of the analytes and
      electroosmotic flow, thereby affecting resolution and speed. Without
      pretreatment, the determinations of five important markers in urine samples and
      two acids in a cerebrospinal fluid sample have been performed separately, with
      the relative standard deviations of the concentrations less than 3.6%.
      Furthermore, by applying a short plug of low-pH buffer after injection, the
      analysis of greater volumes of the urine sample has been carried out, resulting
      in detecting more peaks.

PMID- 12179983
TI  - Profiling isoflavonoids found in legume root extracts using capillary
      electrophoresis.
AB  - Legumes such as alfalfa (Medicago sativa L.), barrel medic (Medicago truncatula),
      white sweet clover (Melilotus alba) and fenugreek (Trigonella graecum), normally
      accumulate (-)-medicarpin and its malonated glucose conjugate as natural
      inhibitors of fungal pathogens. These plants also accumulate the biosynthetic
      precursor formononetin as well as the malonated glycoside. We were interested in
      developing a robust high-throughput method to quantitate the levels of these two
      isoflavonoids, both free and conjugated, in legume root extracts, for use in
      screening for mutant plants accumulating altered levels of these compounds.
      Capillary electrophoresis was examined as an alternative to current high
      performance liquid chromatography (HPLC) methods to generate isoflavonoid
      profiles. The developed assay used micellar electrokinetic capillary
      chromatography (MEKC) to provide the required selectivity in complex root
      extracts. The addition of 1,2-hexanediol to the sodium dodecyl sulfate (SDS)
      electrolyte provided improved resolution of adjacent isoflavonoids. We examined
      the role of several factors including sample preparation, buffer composition,
      buffer pH, and organic component in the injected sample. The use of capillaries
      with longer path lengths were also examined to increase sensitivity. A comparison
      of results obtained using MEKC and HPLC showed good correlation in the relative
      amounts of the isoflavonoids studied.

PMID- 12179984
TI  - A simple mathematical model to aid quantification of electrophoresis gels by
      image analysis.
AB  - In many scientific disciplines, measurements are taken from films that have been
      exposed to energetic sources. Examples include radiographs where the source is an
      X-ray tube, autoradiography where the source is a radioactive isotope and
      electrophoresis gels where the source is an enhanced chemiluminescence reaction.
      In these situations it is of interest to quantify the darkening of the film and
      compute the strength of the source which in the cases of autoradiography and
      electrophoresis can be used to compute unknown concentrations of biochemicals. We
      developed a simple mathematical model of the darkening of films in radiography,
      autoradiography and electrophoresis bands disclosed by enhanced
      chemiluminescence, and present formulae to calculate the strength of the source
      from measurement of film blackening by image analysis. A simple model is used in
      two examples to predict blackening of film exposed to electromagnetic radiation.
      This blackening is measured by image analysis. Results show reasonable agreement
      between predictions of the model and blackening of film for the examples chosen.
      This model is proposed as an aid to quantification of electrophoresis gels.

PMID- 12179985
TI  - Improved separation of integral membrane proteins by continuous elution
      electrophoresis with simultaneous detergent exchange: application to the
      purification of the fusion protein of the human immunodeficiency virus type 1.
AB  - We describe a protocol for preparative-scale purification of the fusion protein
      of the human immunodeficiency virus type 1 (HIV-1), gp41, from cells
      overexpressing the viral envelope proteins and from HIV-1 isolates. In the first
      step, the proteins were extracted from the membrane in sodium dodecyl sulfate
      polyacrylamide gel electrophoresis (SDS-PAGE) sample buffer. The extract was then
      subjected to separation by continuous elution electrophoresis using a nonionic or
      zwitterionic detergent in the mobile elution buffer, which results in the
      simultaneous exchange of SDS with that detergent. The separated proteins were
      obtained in an SDS-free buffer containing either Brij, 3-[(3
      chloramidopropyl)dimethylammonio]-1-propanesulfonate (CHAPS) or Triton X-100 and
      could then be subjected to subsequent purification steps like isoelectric
      focusing in the second dimension or immunoaffinity chromatography. The dilute
      protein fraction was concentrated and applied on a 10 mL immunoaffinity column
      packed with anti-gp41 monoclonal antibody immobilized on protein-G sepharose. The
      protein was eluted from the column at pH 2.7 and obtained in pure form in amounts
      of 30-50 micrograms that constituted a yield of 1%. The pure gp41 could not be
      sustained in solution in the absence of detergent and was not susceptible to
      proteolytic digestion by trypsin. The identification of the protein and the
      degree of purity was confirmed indirectly using surface enhanced laser desorption
      ionization-time of flight-mass spectrometry (SELDI-TOF-MS). The possible
      application of this approach for the isolation of integral membrane proteins with
      the propensity to undergo spontaneous folding and aggregation is being discussed.

PMID- 12179986
TI  - mRNA differential display of gene expression in colonic carcinoma.
AB  - We analyzed changes in gene expression in human colonic carcinoma by fluorescent
      mRNA differential display. RNA isolated from two samples of normal colon and four
      cases of colonic adenocarcinoma were amplified with a 15 x 32 set of primers
      resulting in 2880 cDNAs analyzed with an automated sequencer. Electrophoretic
      patterns implying constitutive gene expression as well as upregulated and
      downregulated expression in carcinomas were identified. Forty such cDNA fragments
      were purified by a novel fluorescent polyacrylamide gel electrophoresis (PAGE)
      based method and identified by cyclic sequencing. Most genes showing differential
      expression were upregulated in colonic carcinoma. Upregulated genes included
      those for various ribosomal and mitochondrial proteins, heat shock proteins,
      nucleolar RNA-helicase and phosphoserine aminotransferase. Downregulated genes
      included histone H3.3. In conclusion, genes associated with vital cellular
      functions such as transcription, protein synthesis and mitochondrial metabolism
      were upregulated in colonic carcinoma. Fluorescent mRNA differential display can
      be applied to the identification of novel cancer-related genes for diagnostic,
      prognostic and therapeutic purposes.

PMID- 12179987
TI  - High-performance capillary electrophoretic method for the quantification of 5
      methyl 2'-deoxycytidine in genomic DNA: application to plant, animal and human
      cancer tissues.
AB  - A new approach to the evaluation of the relative degree of genomic DNA
      methylation through the quantification of 2'-deoxynucleosides is proposed.
      Detection and quantification of 5-methyl 2'-deoxycytidine in genomic DNA has been
      performed using micellar high-performance capillary electrophoresis (HPCE) with
      UV-Vis detection. This approach has been demonstrated to be more sensitive and
      specific than other HPCE methods for the quantification of DNA methylation degree
      and also to be faster than other HPLC-based methods. The detection and
      quantification of nucleosides through enzymatic hydrolyses notably increases the
      specificity of the technique and allows its exploitation in the analysis of
      poorly purified and/or concentrated DNA samples such as those obtained from
      meristematic plant regions and paraffin-embedded tissues.

PMID- 12179988
TI  - Fluorescein-based pI markers for capillary isoelectric focusing with laser
      induced fluorescence detection.
AB  - We prepared a series of low-molecular-mass fluorescent ampholytes with narrow pI
      range. These fluorescein-based ampholytes are detection compatible with argon
      laser-induced fluorescence (LIF) detection. The selected properties, important
      for their routine use as fluorescent pI markers, were examined. The pI values of
      new fluorescein-based pI markers were determined by capillary isoelectric
      focusing (CIEF) using currently available low-molecular-mass pI markers for CIEF
      with photometric detection. The examples of CIEF with fluorometric detection of
      new compounds together with fluorescein isothiocyanate (FITC) derivatized
      proteins are presented.

PMID- 12179989
TI  - Enhanced detection of porphyrins by capillary electrophoresis-laser induced
      fluorescence.
AB  - A highly sensitive technique for the analysis of urinary porphyrins using
      capillary electrophoresis (CE) coupled with laser-induced fluorescence (LIF)
      detection is reported. Separation of mesoporphyrin IX, coproporphyrin,
      uroporphyrin and the penta-, hexa- and heptacarboxylic acid porphyrins was
      achieved in 11 min using a 10 mM 2-(N-cyclohexylamino)ethanesulfonic acid (CHES,
      pH 10) -75 mM sodium dodecyl sulfate (SDS) buffer. Migration time and peak area
      repeatability were less than 1 and 5% relative standard deviation (RSD),
      respectively. Limits of detection of 20 pM (2 x 10(-11) M) were achieved
      employing the recently introduced Nichia violet diode laser for excitation at 400
      nm. This represents an enhancement in sensitivity of over two orders of magnitude
      compared to previous reports. This high sensitivity for urinary porphyrins was
      demonstrated through the quantification of coproporphyrin and uroporphyrin in
      urine samples after up to a 100-fold dilution.

PMID- 12179990
TI  - Development and validation of capillary electrophoresis method for tobramycin
      with precapillary derivatization and UV detection.
AB  - One of the major drawbacks in the analysis of aminoglycoside antibiotics is their
      lack of UV chromophore and/or fluorophore. Tobramycin, a representative member of
      this group, was examined in this study. To overcome the detection hurdle, a
      precapillary derivatization followed by capillary electrophoresis analysis with
      direct UV detection was investigated. A central composite design was applied to
      optimize the method and three parameters were selected in this study: buffer pH,
      temperature and % acetonitrile (ACN). Selectivity between tobramycin main
      component and its adjacent peaks as well as the peak efficiency and symmetry
      factors were established as responses. For each response, a model was obtained by
      a second-order mathematical expression. Successful results were obtained with a
      simple background electrolyte (BGE) containing 30 mM sodium tetraborate, pH 10.2,
      and ACN (75:25 v/v). Under these conditions, baseline separation of tobramycin
      from its adjacent kanamycin B and an unknown peak was achieved. A temperature of
      20 degrees C and applied voltage of 28.0 kV were used. The method showed good
      validation data in terms of precision, limits of quantitation and detection,
      specificity and linearity and was found to be suitable for analysis of tobramycin
      bulk pharmaceutical samples.

PMID- 12179991
TI  - Enantioseparation of novel COX-2 anti-inflammatory drugs by capillary
      electrophoresis using single and dual cyclodextrin systems.
AB  - A capillary electrophoresis method was developed for the enantioseparation of
      three novel cyclooxygenase-2 (COX-2) inhibitor drugs (E-6259, E-6036 and E-6087)
      with anti-inflammatory and analgesic activities using sulfobutyl ether-beta
      cyclodextrin (SBE-beta-CD) as a chiral selector. The use of 50 mM sodium
      tetraborate at pH 9.2 with 30% v/v methanol, containing 7.1 mM SBE-beta-CD, as a
      background electrolyte (BGE) allowed the complete enantioseparation of the three
      neutral racemic mixtures (resolution = 2.4, 3.0 and 8.7, respectively) and their
      corresponding metabolites (oxidation products) in a single run. Migration times
      were shortened with some loss of enantioresolution by adding 1.75 mM dimethyl
      beta-cyclodextrin (DM-beta-CD) to the previous BGE (dual CD system). The reversal
      of the migration order of E-6259 enantiomers in the dual CD system was also
      studied. Furthermore, the addition of DM-beta-CD to the BGE introduced a new
      chemoselectivity in the system that allowed E-6259 to be separated from the
      structurally similar compound E-6036.

PMID- 12179992
TI  - Identification of Leguminosae gums and evaluation of carob-guar mixtures by
      capillary zone electrophoresis of protein extracts.
AB  - A procedure for the extraction and capillary zone electrophoresis (CZE)
      separation of proteins from carob, guar and tara gums in a background electrolyte
      (BGE) of pH 9 containing 0.1% polyvinyl alcohol is described. The CZE protein
      profiles exhibit characteristic peaks for each one of the Leguminosae gums, which
      can be used to construct models capable of identifying samples of carob, guar and
      tara gums, and predicting the guar content in binary carob-guar mixtures of
      different geographical origin and harvested in different years. The
      classification and prediction models are constructed by using linear discriminant
      analysis (LDA) and multiple linear regression (MLR), respectively. An excellent
      resolution between the three categories is obtained with LDA, the model being
      capable of classifying samples with recognition and prediction capabilities of
      100%. For MLR models constructed with carob-guar mixtures with and without a
      common history, the average of the calibration residuals are +/- 0.50 and +/-
      0.90%, respectively (average values for the 2-20% guar range). For the later
      model, the detection limit was 3.2% guar (from the standard deviation of 18
      mixtures with 2-4% guar, and for alpha = beta = 0.05).

PMID- 12179993
TI  - Ultrarapid capillary electrophoresis method for the determination of reduced and
      oxidized glutathione in red blood cells.
AB  - We describe a very rapid high-performance capillary electrophoresis method for
      the separation and quantification of reduced (GSH) and oxidized (GSSG)
      glutathione in red blood cells. Two procedures for sample preparation have been
      compared, Microcon-10 membrane filtration and acid precipitation. The separation
      is obtained in an uncoated capillary using a high ionic strength borate buffer at
      pH 7.8. The intra-assay coefficients of variation (CVs%) are 1.53 and 1.66 for
      GSH and GSSG, respectively. The run is shorter than 90 s and the migration time
      is highly reproducible both for GSH (CV% 0.22) and GSSG (CV% 0.17). When the
      filtration step is used only GSH is found, whereas both GSH and GSSG are
      detectable after acid precipitation, suggesting that GSSG revealed after acid
      treatment may be an artefact due to GSH oxidation. Because of its good analytical
      performance this method could be used for routine red blood cell glutathione
      measurement in healthy or pathological conditions.

PMID- 12179994
TI  - A polydimethylsiloxane/glass capillary electrophoresis microchip for the analysis
      of biogenic amines using indirect fluorescence detection.
AB  - A polydimethylsiloxane-glass capillary microchip is fabricated for the rapid
      analysis of a mixture of common biogenic amines using indirect fluorescence
      detection. Using a running buffer of phosphate and 2-propanol, and Rhodamine 110
      as a background fluorophore, both co-ionic and counter-ionic systems are
      explored. Studies demonstrate the separation and analysis of cations using
      indirect fluorescence detection for the first time in a chip-based system.
      Resulting electrophoretic separations are achieved within a few tens of seconds
      with detection limits of approximately 6 microM. The reduced sample handling and
      rapid separations afforded by the coupling of indirect fluorescence detection
      with chip-based capillary electrophoresis provide a highly efficient method for
      the analysis and detection of molecules not possessing a chromophore or
      fluorophore. Furthermore, limits of detection are on a par with reported chip
      based protocols that incorporate precolumn derivatisation with fluorescence
      detection. The current device circumvents lengthy sample preparation stages and
      therefore provides an attractive alternative technique for the analysis biogenic
      amines.

PMID- 12179995
TI  - Warping two-dimensional electrophoresis gel images to correct for geometric
      distortions of the spot pattern.
AB  - A crucial step in two-dimensional gel based protein expression analysis is to
      match spots in different gel images that correspond to the same protein. It still
      requires extensive and time-consuming manual interference, although several
      semiautomatic techniques exist. Geometric distortion of the protein patterns
      inherent to the electrophoresis procedure is one of the main causes of these
      difficulties. An image warping method to reduce this problem is presented. A
      warping is a function that deforms images by mapping between image domains. The
      method proceeds in two steps. Firstly, a simple physicochemical model is
      formulated and applied for warping of each gel image to correct for what might be
      one of the main causes of the distortions: current leakage across the sides
      during the second-dimensional electrophoresis. Secondly, the images are
      automatically aligned by maximizing a penalized likelihood criterion. The method
      is applied to a set of ten gel images showing the radioactively labeled proteome
      of yeast Saccharomyces cerevisiae during normal and steady-state saline growth.
      The improvement in matching when given the warped images instead of the original
      ones is exemplified by a comparison within a commercially available software.

PMID- 12179996
TI  - Inhibition of unwanted proteolysis during sample preparation: evaluation of its
      efficiency in challenge experiments.
AB  - Measures to counteract proteolysis during sample preparation are widely used;
      among them, protein extraction at a basic pH (Tris pH 11.0), sample boiling in
      sodium dodecyl sulfate (SDS), extraction in denaturing lysis solutions and the
      use of proteinase inhibitors combined with some of these approaches. Here, we
      tested their efficiency under stringent conditions using a high proteinase
      (trypsin and a mixture of pancreatic proteinases) contamination and as substrate,
      streptokinase, a protein highly sensitive to proteolytic degradation. Total
      degradation was observed in Tris pH 11.0. There was an efficient inhibition for
      the pancreatic proteinases after boiling in 1% SDS, 1% dithiothreitol (DTT),
      while trypsin inhibition was dependent on the enzyme-to-substrate ratio. A panel
      of 21 lysis solutions with variable concentrations of urea, thiourea and
      detergents was essayed for the ability to counteract proteolysis. In all
      solutions containing 7-9 M urea, detergents and proteinase inhibitors but not
      containing thiourea, there was a strong proteolysis. However, in all samples
      containing 2 M thiourea, proteolysis was inhibited. Moreover, inhibition was
      dependent on the thiourea concentration. According to these results, we are
      prompted to consider that the well-known benefits of incorporating thiourea into
      the lysis solution are a result of two factors, its efficiency in solubilizing
      proteins and the inhibition of the proteolysis of sensitive substrates; both
      contributing to the detection of a higher number of species in two-dimensional
      electrophoresis (2-DE) gels.

PMID- 12179997
TI  - Proteomic analysis of the Arabidopsis thaliana cell wall.
AB  - With the completion of the Arabidopsis genome, many hypothetical proteins have
      been predicted without any information on their expression, subcellular
      localisation and function. We have performed proteomic analysis of proteins
      sequentially extracted from enriched Arabidopsis cell wall fractions and
      separated by two-dimensional gel electrophoresis (2-DE). The proteins were
      identified by peptide mass fingerprinting using matrix-assisted laser
      desorption/ionisation-time of flight (MALDI-TOF) mass spectrometry and genomic
      database searches. This is part of a targeted exercise to establish the entire
      Arabidopsis secretome database. We report evidence for new proteins of unknown
      function whose existence had been predicted from genomic sequences and,
      furthermore, localise them to the cell wall. In addition, we observed an
      unexpected presence in the cell wall preparations of proteins whose known
      biochemical activity has never been associated with this compartment hitherto. We
      discuss the implications of these findings and present results suggesting a
      possible involvement of cell wall kinases in plant responses to pathogen attack.

PMID- 12179998
TI  - [The role of repeated biopsies in prognosis of prostate cancer].
AB  - INTRODUCTION: The treatment of prostate cancer is still controversial. One of the
      most common treatment form is the use of LHRH analogs, but its way of action is
      still not cleared enough. AIMS: The aim of this study was to determine the
      predictive value of some histological and immuno-histochemical parameters based
      on repeated biopsies taken from prostate carcinoma patients. PATIENTS/METHOD: At
      the time of diagnosis by needle biopsy the TNM stage, serum PSA level, Gleason's
      grade, apoptotic and mitotic index, as well as Ki67, p53 and bcl2 expression were
      investigated in 60 prostate carcinoma patients. Anti-androgen therapy
      supplemented with surgical or chemical castration (with LHRH analogs) was
      administered. Serum PSA-test and needle biopsy were repeated 13-14 weeks after
      starting the therapy, simultaneously with determination of the apoptotic and
      mitotic index, Ki67, p53 and bcl2 expression. RESULTS: Forty-seven patients were
      alive at the end of the study (average 23.46 +/- 8.6 months) and thirteen
      patients died (average 25.3 +/- 14.8 months). Initial TNM stage and Gleason's
      score proved to be of prognostic value. Decrease in mitotic index and increase in
      apoptotic index during therapy proved to predict favourable long-term response to
      androgen ablation therapy. Similarly, lower Ki67 and (mutant) p53 expression in
      the first and also in the second biopsy pointed to a favourable effect of
      antiandrogen and especially of LHRH analog treatment. Since the ratio between
      Ki67 percentage and apoptotic index strongly decreased in the survivors upon
      therapy, changes in Ki67/apoptosis ratio may be recommended as a histologically
      detectable predictive factor. However, bcl2 expression did not show significant
      correlation with the outcome of the disease. CONCLUSION: Histological evaluation
      of parameters such as mitotic and apoptotic index as well as Ki67 and p53
      expression in repeated biopsies during treatment may contribute to predicting the
      value of the actual treatment and may be useful to institute alterations in
      therapy.

PMID- 12179999
TI  - [Cerebral edema and changes of cerebral blood volume in patients with head
      injuries].
AB  - AIM: The pathogenesis of traumatic brain swelling remains unclear. The generally
      held view is that brain swelling is caused primarily by vascular engorgement and
      that edema plays a relatively minor role in the swelling process. The goal of
      this study was to examine the roles of cerebral blood volume (CBV) and edema in
      traumatic brain swelling. PATIENTS AND METHODS: Both brain-tissue water and CBV
      were measured in 76 head-injured patients, and the relative contribution of edema
      and blood to total brain swelling was determined. Comparable measures of brain
      tissue water were obtained in 30 healthy volunteers and CBV in seven volunteers.
      Brain edema was measured using magnetic resonance imaging, implementing a new
      technique for accurate measurement of total tissue water. Measurements of CBV in
      subgroup of 31 head-injured patients were based on consecutive measures of
      cerebral blood flow (CBF) obtained using stable xenon and calculation of mean
      transit time by dynamic computerized tomography scanning after a rapid bolus
      injection of iodinated contrast material. RESULTS: The mean (+/- standard
      deviation) percentage of swelling due to water was 9.37 +/- 8.7%, whereas that
      due to blood was -0.8 +/- 1.32%. CONCLUSION: The results of this study showed
      that brain edema is the major fluid component contributing to traumatic brain
      swelling. Moreover, CBV is reduced in proportion to CBF reduction following
      severe brain injury.

PMID- 12180000
TI  - [Frequency of hyperhomocysteinemia in hemodialysis patients with folic acid
      supplementation].
AB  - BACKGROUND: It is known that hyperhomocystinemia is an independent risk factor
      for development of atherosclerosis. In end stage renal disease the frequency of
      hyperhomocystinemia is much greater than in normal populations. AIM: In this
      study homocystein (Hcy), folic acid and vitamin B12 concentrations were
      determined in 125 chronic renal failure patients being on folic acid
      supplementation (3 mg/day). In 107 patients the frequency of C667T polymorphism
      of methylene tetrahyrofolate reductase (MTHFR) was also determined. The
      relationships between these parameters were also studied. RESULTS: It was found
      that in these patients who are under continuous folic acid supplementation the
      mean level of homocysteine was 16.8 +/- 7.2 mumol/L, a value considerably lower
      than the homocysteine concentration reported for non-supplemented patients. The
      elevation of homocysteine concentrations was independent of gender, time spent in
      renal replacement therapy, and the type of renal replacement therapy
      (hemodialysis: 17.6 +/- 12.6; hemodiafiltration: 16.6 +/- 12.9 mumol/L). Data
      showed an inverse relation between plasma homocysteine concentrations and the
      concentrations of folic acid and vitamin B12. Moderately severe
      hyperhomocystinemia (Hcy > 20 mumol/L) was found in about 30% of patients. In
      those the frequency of patients for homozygous T677 allele of MTHFR was about 25
      30%. However, in all ESRD patients the frequency of the homozygotes was the same
      then in the normal population. Homocysteine plasma levels correlated with MTHFR
      polymorphism: in the wild type group Hcy was 14 +/- 7 mumol/L, in the
      heterozygous group was 17.2 +/- 6.2 mumol/L, and in the homozygous group was 21
      +/- 19 mumol/L. CONCLUSIONS: Long-term folic acid supplementation decreased the
      homocysteine level in end stage renal disease patients. However, in folic acid
      resistant group, who were in 30% homozygotes for C667T of MTHFR (suggesting that
      homocysteine-methionine remethylation cycle is disturbed), instead of the
      administration of folic acid, methylene tetrahydrofolate supplementation might be
      considered.

PMID- 12180001
TI  - [Prophylaxis and therapy of gastropathy caused by non-steroidal anti-inflammatory
      drugs].
AB  - INTRODUCTION: The main disadvantage of the nonsteroidal anti-inflammatory drugs
      (NSAID) is their toxic effect on the gastroduodenal mucosa, which can cause life
      threatening complications. AIMS: We discuss the possibilities to prevent the
      harmful effect of the NSAIDs: the use of safer NSAIDs, and the co-therapy with
      protective mechanisms. METHODS: Among the safer NSAIDs we discuss the
      preferentially selective, and the highly selective COX-2 inhibitors, and the new,
      nitric-oxide releasing NSAIDs. We consider the role of the mucosa-protecting
      mechanisms: antacids, sucralfate, H2 receptor antagonists, proton-pump
      inhibitors, and misoprostol. CONCLUSIONS: The most effective opportunities to
      protect the gastroduodenal mucosa--which is highly recommended for the high risk
      group of patients--are the usage of highly selective NSAIDs, or the concomitant
      therapy with proton-pump inhibitors or misoprostol. The value of the letter is
      diminished by it's side effects.

PMID- 12180003
TI  - [Hemopoiesis on stromal sublayers formed by constant lines of fibroblasts].
AB  - We studied the formation of hemopoietic colonies on an artificial sublayer in the
      peritoneal cavity of mice under the influence of stromal sublayers consisting of
      fibroblasts of six constant cell limes. All studied lines of stromal cells
      supported the formation of granulocytic foci and some of them supported the
      formation of erythroid foci as well. It was shown that hemopoiesis was preserved
      or, in some cases, enhanced on sublayers of fixed (metabolically inactive) cells.
      The treatment of fibroblasts by E. coli lipopolysaccharide did not lead, as a
      rule, to significant stimulation of hemopoiesis.

PMID- 12180004
TI  - [Effect of continuous gamma-radiation at low doses on clonogenic hemopoietic (CFU
      S) and stromal (CFU-F) bone marrow cells ].
AB  - We studied the effects of low doses of continuous gamma-irradiation (Co60, 10
      days, mean daily dose power 1.5-2.0 mGy, total dose 15 mGy) on hemopoietic and
      stromal progenitor cells of murine bone marrow. The content of hemopoietic
      clonogenic cells representing a "younger" (CFU-S-11) and more "mature" (CFU-S-7)
      categories in the compartment of stem cells was determined in the bone marrow.
      The state of bone marrow stroma was estimated by the method of in vitro cloning
      according to the number of progenitor cells that form colonies of fibroblasts
      (CFU-F) and by the method of ectopic transplantation according to the capacity of
      stroma of organizing and building new hemopoietic territories. Continuous gamma
      irradiation at low doses, that were by one order of magnitude lower than those
      inducing hermesis, exerted a stimulating effect on both hemopoietic (CFU-S) and
      stromal (CFU-F) progenitor cells. The number of CFU-S in the compartment of stem
      cells of the bone marrow markedly increased and they formed larger hemopoietic
      territories but these cells appeared to create a qualitatively different
      microenvironment, which stimulated the proliferation of CFU-S.

PMID- 12180002
TI  - [Isolated left ventricular noncompaction--first description in a Hungarian
      patient].
AB  - The case of a young female patient is presented in whom the typical diagnostic
      features of isolated ventricular noncompaction were recognized by two-dimensional
      echocardiography after 11 year follow-up. This rare cardiomyopathy is
      characterized by prominent trabeculations of the apex and the distal lateral wall
      of the left ventricle, systolic dysfunction, restrictive dysfunction, functional
      mitral and tricuspid insufficiency. Literature review reveals the underlying
      abnormality of the myocardial embryogenesis with a delayed presentation in
      adulthood and variable clinical manifestations ranging from long asymptomatic
      periods to malignant courses including sudden death, transplantation and
      decreased survival.

PMID- 12180005
TI  - [The role of cell proliferation in tubulogenesis of human keratinocytes].
AB  - We studied kinetics and role of keratinocyte proliferation in the process of
      cysto- and tubulogenesis of human postnatal epidermal keratinocytes in collagen
      gel. The influence of media conditioned by embryonic and postnatal fibroblasts on
      morphogenesis has been comparatively analyzed. We studied the influence of
      proliferation inhibitors and inductors on tubulogenesis. The obtained data
      indicate partial dissociation of migration, proliferation, and differentiation of
      keratinocytes during morphogenetic processes in culture. We propose a new model
      considering proliferation of epithelial cells during cysto- and tubulogenesis.

PMID- 12180006
TI  - [Fibroblasts stimulate epithelialization of collagen gel].
AB  - We studied the influence of human embryonic fibroblasts on epithelialisation of
      collagen gel. Introduction of the fibroblasts into the gel stimulates
      proliferation of keratinocytes plated on the gel surface. The presence of
      fibroblasts in the gel also affects the pattern of keratinocyte migration on the
      gel and induces pronounced polarization of the migrating colonies.

PMID- 12180007
TI  - [An immunohistochemical study of localization of the calcium-binding protein
      recoverin in retina of the newt Pleurodeles waltl].
AB  - The presence and localization of the calcium-binding protein recoverin, initially
      found in photoreceptors of the bovine eye, were immunochemically studied in
      retina of the new Pleurodeles waltl. Polyclonal monospecific antibodies against
      recoverin were raised and the methods of immunoblotting and indirect
      immunofluorescence were used. A protein with an apparent molecular mass of 26 kDa
      was found in the retina extract, which was specifically stained by the antibodies
      against recoverin. Localization of recoverin was studied on the retina sections:
      an intense reaction was found in the inner segments and a weak reaction was found
      in the basal part of the outer segments of photoreceptors and in Landolt's clubs
      of displaced bipolars. The results we obtained suggest for the first time the
      presence of recoverin in the retina of a representative of the Urodeles and
      indicate to interspecific conservativeness of this protein and differences of its
      localization in the retina photoreceptors in different species. The data obtained
      open a possibility of using recoverin as a marker protein of photoreceptors and
      displaced bipolars in studied of retina regeneration in newts.

PMID- 12180008
TI  - [The mechanism of bactericidal activity in phagosomes of neutrophils].
AB  - Myeloperoxidase plays the key role in antimicrobial of phagocytes. This enzyme
      uses hydrogen peroxide and chloride to catalyze hypochlorous acid formation. HOCl
      is the most probable agent in the oxygen-dependent bactericidal activity in the
      phagocyte phagosome. Chlorination markers indicate HOCl generation in the
      quantities lethal for bacteria. Enzymatic assay for myeloperoxidase indicates
      proceeding of other reactions involved in bactericidal activity. Superoxide
      integrates many activities of this kind and is important for physiological
      function of myeloperoxidase. Elucidation of phagosomes biochemistry can help us
      to understand why certain pathogens survive in such unfavorable environment.

PMID- 12180009
TI  - [Pattern of formation of nuclear chromosomal apparatus after remote hybridization
      in wheat and buckwheat: effect of low temperature].
AB  - We studied the pattern of embryo formation in wheat and buckwheat interspecific
      hybrids. Formation of non-reduced gametes in the embryo sac was induced by low
      temperature (4-7 degrees C). Changed thermal conditions during meiosis proved to
      favor formation of hybrid embryos. Vital embryos have been obtained. Karyotypic
      analysis on the metaphase plates from the root meristem demonstrated different
      genotypes. Heterogeneous embryos caring both maternal and paternal chromosomes as
      well as the embryos caring solely maternal or paternal chromosomes have been
      revealed. Spermatozoa penetrate the embryo sac as a cell, which increases
      aminopeptidase activity. Sometimes low temperature induces formation of somatic
      embryos from nucellus cells in the plants.

PMID- 12180010
TI  - [Cycloheximide induced decrease in frost resistance of winter wheat is mediated
      by inhibition of adaptive rearrangement of the cell and chloroplast structure].
AB  - Cycloheximide in the concentration inhibiting protein synthesis and frost
      resistance of plants proved to prevent formation of cell and chloroplast
      structures specific for the plants adapted to frost. Important role of structural
      rearrangement of the cells during hardening preventing intracellular ice
      nucleation is proposed.

PMID- 12180011
TI  - [Analysis of mechanisms underlying adaptation processes].
AB  - A system of elementary adaptation mechanisms is presented. The adaptations are
      considered as transients to a new homeostatic condition induced by an
      environmental change. We propose to distinguish adaptation mechanisms not
      directly related to gene expression (changes in the rate of synthesis and
      degradation of proteins, protein-ligand interactions, changes in viscosity of the
      membrane lipids) and the mechanisms relying on gene expression (changes in
      expression of already functioning genes, expression of new genes, mutations).
      Most of these mechanisms have phenotypic nature and just one (mutations) is
      genotypic. By the nature and time pattern of the environmental influence the
      adaptation processes can be divided into four types: phenotypic adaptations under
      rapidly (A) or gradually (B) alternating environmental factors, genotypic
      adaptations induced by an instant change (mutation) (C), and step adaptational
      changes (several or many mutations) (D). We propose a model based on a (second
      order) linear differential equation qualitatively describing all four types of
      the adaptation processes.

PMID- 12180012
TI  - [Morphofunctional organization of lymphoepithelial organs of the human pharynx].
AB  - We present the current concepts of morphofunctional organization of the
      lymphoepithelial organs in the human pharynx based on the published data and
      authors' results. Functional compartmentation of palatine and pharyngeal tonsils
      is considered, which reflects cooperative cell interactions in the immune
      response; B- and T-areas have been structurally isolated and functionally
      substantiated. A special attention is paid to the fine structure of cryptal
      epithelium and its interactions with lymphoid cells infiltrating the epithelial
      sheet: lymphoepithelial symbiosis. Attention is also paid to structural homology
      of the lymphoepithelial compartment of palatine tonsils and thymus. The problem
      concerns the place of lymphoepithelial organs in hierarchy of the immune system
      as secondary organs with their own immunoregulatory area and having the functions
      of a regional center controlling the mucosal immunity.

PMID- 12180013
TI  - [Effect of structural changes of Pro6 in dermorphin molecule on its
      antinociceptive activity].
AB  - We studied effect of dermorphin (H-Tyr-DAla-Phe-Gly-Tyr-Pro-Ser-NH2) and its
      analogs with modified amino acid residue proline in position 6, H-Tyr-DAla-Phe
      Gly-Tyr-[DPro]-Ser-NH2, H-Tyr-DAla-Phe-Gly-Tyr-[dehydro-Pro]-Ser-NH2, and H-Tyr
      DAla-Phe-Gly-Tyr-[D-dehydro-Pro]-Ser-NH2, on nociception in the tail-flick and
      hot plate tests after intraperitoneal injection. Replacement of LPro with the
      stereoisomer DPro as well as Pro dehydration (LdHPro) was shown to increase
      antinociceptive activity. Replacement of LdHPro with DdHPro cancelled the
      activity in the tail-flick test. All three dermorphin analogs retained
      antinociceptive activity in the hot plate test; however, the effect of dermorphin
      was more pronounced.

PMID- 12180014
TI  - [New biological properties of p-aminobenzoic acid].
AB  - p-Aminobenzoic acid (PABA) is a cyclic amino acid, belongs to the vitamin B
      group, and is used as a protective drug against solar insolation and in
      diagnostic tests for the state of the gastrointestinal tract in medicine. We were
      the first to establish that PABA is an inducer of endogenous interferon and
      immunomodulator and displays a virucidal, synergistic antiviral effect when
      combined with chemical drugs and the properties of a direct anticoagulant. Based
      on these properties, we elaborated a new medicinal drug "Actipol" which was
      introduced in clinical practice.

PMID- 12180015
TI  - [Morphobiochemical adaptations to life on littoral in some sedentary gastropods].
AB  - Adaptations to attachment, respiration, nutrition, and pollution of sedentary
      gastropods with cowl-shaped shell living in littoral conditions and prone to the
      influence of abiotic factors are analyzed. Weight properties of individual parts
      of the radular apparatus related to scrapping mode of nutrition are discussed.
      The content of hemoglobin in radular tissues of some representatives of
      Patellidae, Acmaeidae, and Siphonariidae families is comparatively evaluated.

PMID- 12180016
TI  - [Heterogeneity and polymorphism of functionally specialized blood proteins of
      migratory fish based on the example of the North Caspian population of Russian
      sturgeons during the sea and river periods of life. 2. Hemoglobins].
AB  - We carried out comparative studies of the heterogeneity and polymorphism of the
      most important functionally specialized blood proteins, hemoglobins. The
      fractional composition of hemoglobin proved to be identical during the sea and
      river periods of life for all main parameters (number of components, relative
      mobility, and protein content of each component). This puts the Russian sturgeon
      in a special position with reference to migratory teleostean fish, specifically
      salmonids, in which the specific weight of the protein of "slow" and "fast"
      hemoglobins undergoes changes upon change of the habitat.

PMID- 12180017
TI  - [On bacterial origin of mitochondria in eukaryotes in the light of current ideas
      of evolution of the organic world].
AB  - The hypothesis of bacterial origin of mitochondria, which existed until the end
      of the 20th century, has been confirmed on the basis of the current concepts of
      organic world evolution in the open sea hydrosphere and original data on the
      entry of bacteria (prokaryotes0 in the cells of eukaryotes and their
      transformation into the mitochondrial mechanism of aerobic energy metabolism.
      This hypothesis can now be considered as a factually substantiated theory. The
      process of endocytosis of bacteria in the tissues of eukaryotes, which began at
      the onset of transition of the anaerobic state of open sea hydrosphere and land
      atmosphere (Early Proterozoic), is considered as the beginning of symbiotic mode
      of life of organisms of the Proterozoic and Postproterozoic organic world.

PMID- 12180018
TI  - [Study of PGM mutation mechanism in Yersinia pestis (plague pathogen) vaccine
      strain EV76].
AB  - Yersinia pestis vaccine strain EV76 is a mutant of the virulent strain which has
      lost the pigmentation phenotype (Pgm+). This phenotype includes three
      characteristics: it absorbs pigments from agar media (Hms+), produces a
      siderophore yersiniabactin (Ybt+), and causes a lethal disease after subcutaneous
      inoculation of laboratory animals (Vir+). These characteristics are lost
      simultaneously after high frequency spontaneous deletion of 10 kB fragment of
      chromosomal DNA, termed the pgm locus. We compared the pgm locus-associated
      genetic and phenotypical properties of the vaccine strain with those of a typical
      Pgm- deletion mutant of a virulent strain. The results indicate that Pgm-
      phenotype of the vaccine strain results not from the deletion of the pgm locus,
      but from the insertion inactivation of the genes located in this locus. In
      contrast to the deletion mutant, the vaccine strain carries sequences detected by
      hybridization and PCR, which are complementary to the pgm locus genes. Moreover,
      the vaccine strain differed from the deletion mutant by a low level of Hms+
      expression, a slower rate of cell death under iron-chelated conditions at 37
      degrees C, "residual virulence" upon subcutaneous inoculation, and capacity to
      form revertants which restore the characteristics of Pgm+ phenotype after cell
      growth at 12 degrees C.

PMID- 12180019
TI  - [Cloning and expression of 7.55 kb KPNI fragment of Burkholderia pseudomallei
      PPM1 plasmid in Escherichia coli].
AB  - BamHI, SalI, PstI, and KpnI fragments of pPM1 (B. pseudomallei 12.95 kb plasmid)
      were cloned in E. coli. The recombinant clones carrying a 7.55 kb KpnI fragment
      of pPM1 were highly resistant to several aminoglycosides (streptomycin,
      kanamycin, and gentamycin) and fluoroguinolones (perfloxacin, ofloxacin). Two
      outer membrane proteins (23 and 27 kDa) absent in E. coli and capable to form 120
      kDa oligomer complex were detected by the Western blot method in the strain
      carrying recombinant pS19 plasmid. The integration of a cloned 7.55 kb sequence
      in the chromosome was observed by the dot and Southern hybridization analysis in
      the clones carrying recombinant plasmids pS12 and pS14.

PMID- 12180020
TI  - [RNA transduction by phage MS2 noninfectious virions].
AB  - Two fragments (1.9 and 1.8 kb) including, respectively, "structural" genes (A, B,
      and lysis polypeptide) and "replicase" gene, were obtained by reverse
      transcription PCR on the template of bacteriophage MS2 genome RNA. The fragments
      contained a common sequence which allowed the assembly of the entire functional
      genome sDNA. 1.8 kb fragment was subjected to two independent modifications: 1)
      so that the replicase gene could be replaced by other sequences no more than 1.5
      kb in size and 2) it was inserted (on an artifician Tn-like structure) into E.
      coli chromosome. A system for replication of MS2-like corpuscles was thus
      created, containing a "shortened" genome and having extra genes. For extra genes,
      aminoglycoside-3'-phosphotransferase (kanamycin resistance) or a sequence of
      antiviral genetic program directed against hepatitis C virus were used.

PMID- 12180021
TI  - [Submicroscopic characteristics of Marburg virus and its mini genome analog
      replication in cell cultures].
AB  - Marburg virus (Filoviridae) causes severe hemorrhagic fevers in humans and some
      lower primates with high mortality. The virus genome is formed by a single strand
      RNA of negative polarity, coding for seven structural proteins. We studied the
      ultrastructure of Marburg virus replicative cycle and replication of its
      minigenome RNA (coding for the terminal areas of the genome) in the presence of
      helper virus in VERO fibroblastoid cell culture and epithelioid MDCK cell
      culture. Ultrastructural parameters of Marburg virus multiplication in these cell
      cultures are virtually the same. The virus nucleocapsid assembly is performed on
      the outer side of EPR membrane and is not associated with preliminary
      accumulation of the precursor material. Virions form by budding on plasmalemma
      and are located on the entire surface in Vero cells and only on the basolateral
      surface of MDCK cells. Replication of minigenome analog of marburg virus is
      associated with impairment of the helper virus morphogenesis and formation of
      spherical pseudoviral particles.

PMID- 12180022
TI  - [DNA technology for diagnosis and characterization of agricultural animal
      pathogenic viruses].
AB  - Use of recombinant DNA for the development of diagnostic and therapeutic and
      preventive drugs became one of the priority trends in modern experimental
      veterinary. This paper discusses modern methods of virus analysis based on the
      DNA technologies: restriction mapping, nucleic acid hybridization, and polymerase
      chain reaction. Examples of utilization of these methods for clinical diagnosis
      and research of animal viruses are offered.

PMID- 12180023
TI  - [Eukaryotic vectors of Celo avian adenovirus genome, carrying GFP and human IL-2
      genes].
AB  - Recombinant CELO avian adenoviruses carrying green fluorescent protein (GFP) and
      and human interleukin-2 (IL-2) genes were obtained by homologous recombination in
      cell culture. The resultant recombinant CELO viruses are reproduced in chick
      embryos in the renal tubular and chorionic allantoic membrane cells. The ability
      of CELO vectors to transduce human and animal cells was studied in vitro (in cell
      cultures) and in vivo (in laboratory animals). GFP gene delivery and expression
      in recombinant CELO virus in tumors in C57BL/6 mice were for the first time
      demonstrated for B16 melanoma. Human IL-2 gene expression and protein
      accumulation in allantoic fluid of chick embryos infected with CELO-IL-2 vector
      were detected for the first time.

PMID- 12180024
TI  - [Effect of 5-azacytidine on expression of DNA sequences homologous to ENV gene of
      murine mammary tumor virus in normal human lymphocytes].
AB  - Expression of DNA sequences, related to MMTV env gene, in peripheral blood
      lymphocytes, which was strictly specific for human mammary carcinoma, has been
      previously reported. These sequences (homologous to env gene site coding for MMTV
      gp52 envelope antigen) expressed in T cells can play the key role in virus
      infection transmission and propagation. In order to elucidate the possible routes
      of env MMTV-homologous sequences expression, we tried to induced it in donot T
      lymphocytes by various methods: hormone and virus treatment (related genome
      "saving" at the expense of the added virus envelope), T cell culturing with conA,
      interferon-2, and 5-azacytidine. RT-PCR with primers specific for the gp52-coding
      area of MMTV env gene showed expression of env-homologous sequences in donor T
      cells cultured in medium with 5-azacytidine. Indirect immunofluorescence with
      monospecific serum to MMTV gp52 detected gp52 analogous genes only in cultures
      with 5-azacytidine but not other agents. We therefore suggested that MMTV env
      homologous sequences in donors are situated in the methylated promoter zone.
      Expression of these sequences in T cells, specific for human mammary carcinoma,
      can be due to demethylation of the promoter and induction of env-homologous
      sequences to the level of translation of gp52 analogous antigens or by initial
      location of some of the expressed sequences in the demethylated zone of the
      genome.

PMID- 12180025
TI  - [Alteration of cholera toxin biosynthesis in Vibrio cholerae 01 as a result of
      temperate phage 139 integration into bacterial chromosome].
AB  - Infection of V. cholerae 01 (classical and eltor biovars) cells with the
      temperate cholera phage 139 derived from V. cholerae serogroup 0139 followed by
      integration of the phage genome into the bacterial chromosome significantly
      increased the production of cholera toxin, the main virulence factor. The level
      of toxin biosynthesis in the lysogenic V. cholerae classical strain increased 3
      fold and that in V. eltor thirty times in comparison with the parental strains.
      Increased production of cholera toxin was not associated with an increase in the
      number of copies of genes involved in its biosynthesis but seemed to be due to
      changes in toxinogenesis regulation.

PMID- 12180026
TI  - [Image of the month. De-insertion of a prosthetic mitral ring in the course of
      mitral valvuloplasty].

PMID- 12180027
TI  - [How I treat...pityriasis rubra pilaris].
AB  - Pityriasis rubra pilaris is a syndrome of unknown etiology. Six distinct clinical
      types have been described in infancy and adulthood. Oral retinoids have proven
      their efficacy. Emollients and topical calcipotriol may improve the clinical
      presentation.

PMID- 12180028
TI  - [Clinical case of the month. Management of thoracic empyema].
AB  - Adequate management of thoracic empyema implies prompt diagnosis, the application
      of simple treatment algorithm, and the avoidance of the complications of the
      chronic stage. A case report of a typical case of thoracic empyema is an
      opportunity to review the management of this affection.

PMID- 12180029
TI  - [Hypertension and arteriopathy].
AB  - High blood pressure as other factors of atherosclerosis is a well-known risk
      factor for development of peripheral arterial disease. A patient characterized by
      an isolated systolic hypertension and a low ankle/arm systolic blood pressure
      ratio very often presents coronary heart disease. Practising exercise (such as
      walking), stoping smoking and following an adapted diet are recommended.
      Hypertension treatment must be considered as a secondary prevention approach with
      a blood pressure normalisation as a target. All the different classes of
      antihypertensive drugs can be used, but with a marked preference for angiotensin
      converting enzyme (with caution for the renal artery stenosis risk) and for
      betablockers to improve the potential coronary heart disease (care is needed in
      the presence of severe peripheral arterial disease).

PMID- 12180030
TI  - [Pituitary diseases in elderly patients with chronic renal insufficiency].
AB  - Chronic renal failure (CRF) in the elderly is a cause of multiple endocrine
      dysfunctions. The three most common pituitary axes involved are the thyrotrope,
      lactotrope and gonadotrope axes. Thyroid dysfunction may be the consequence of
      thyroid or pituitary failure. Hyperprolactinemia results in gonadal failure and
      is present in 30% of patients. Early presentation of menopause and andropause are
      common in patients with CRF. Sexual hormonal replacement is controversial and
      must be individually tailored. We propose a systematic screening in the elderly
      with CRF: determination of TSH, TPO antibodies and cervical palpation, measures
      of PRL, LH, FSH and testosterone to explore lactotrope and gonadotrope axis.

PMID- 12180031
TI  - [Hypnosis for treatment of nausea and vomiting: it works!].
AB  - We report a case of uncontrollable vomits in 76-year-old patient, for which
      hypnosis was effective. Described vomits became initiated by administration of
      morphine per os, lasted three months and stood up to usual medication as well
      attempts of nutrition by ballasted micro-tube. Somatic etiology search was
      unsucceSsful; the growing significance of hypnosis in the field of anesthesia led
      to use relational and oriented solution therapy. The situation was rapidly and
      constantly solved.

PMID- 12180032
TI  - [Surveillance and side-effects of transfusions].
AB  - Allogenic blood transfusion may be required for the treatment of anemia due to a
      hematologic disease, the consequences of chemotherapy or other circumstances,
      such as haemorrage and/or surgery. Transfusion becomes indispensable to prevent
      the side effects of anemia, such as hypoxia, palpitations, tachycardia, cardiac
      ischemia and fatigue. However, frequent transfusions can cause several acute
      problems such as hemolysis, anaphylactic shock and septic shock but also chronic
      problems such as iron overload (hemochromatosis), alloimmunisation and metabolic
      disturbances. Each of these complications can produce serious consequences and
      could even be sometimes fatal. Therefore we should recognise, prevent and if
      necessary treat all these hazards. Our article emphasises the potential chronic
      problems. For hemochromatosis, an iron chelator (deferoxamine) should be
      administered. In the presence of allo-immunisation the more compatible ABO blood
      group must be chosen and blood products be eliminated by filtration, when there
      has been blood reaction. When an allo-graft of hematopoitic tissues is considered
      an irradiation of blood products is necessary. Research is being carried out to
      develop substitute products for transfusion (haemoglobine solutions) or molecules
      acting on the syntheses of haemoglobine (butyrate arginine). The efficacy of
      erythropoitine, (EPO) is well recognised for stimulation of haemoglobine
      syntheses in renal failure and oncology.

PMID- 12180033
TI  - ["Take this heart away!": from fear of rejection to post-transplant delirium].
AB  - Orthotopic heart transplantation is a major surgical intervention inducing
      conscious and unconscious psychological distress. Though all reports indicated
      global improvement of quality of life from pre- to post-transplantation, most
      retrospective and longitudinal studies found a high prevalence of psychopathology
      before and after surgery. Post-operative acute psychotic disorders are uncommon
      but they severely hamper the medical progress and require an immediate
      psychiatric assistance. The case of Pascal, a young receiver who presented a
      brief persecution delusional disorder after the first transplantation, showed the
      dramatic character of such unexpected symptoms.

PMID- 12180034
TI  - [Mandibular osteoradionecrosis: sword of Damocles of radiotherapy for head and
      neck cancers?].
AB  - Radiotherapy of head and neck cancer is efficient but may have severe late
      effects. Although unfrequent, mandibular radionecrosis is the most dreadful. A
      cascade of events leads from hyposialia to bone destruction through extensive
      caries and trauma linked to tooth removal. Prevention is based on oral hygiene
      and use of daily topical fluorides. Antibiotics and hyperbaric oxygen can be
      effective as a conservative management. Progressive osteonecrosis is best treated
      by mandible resection and reconstruction with microvascular free bone flaps.
      Patient compliance to prophylaxis is of major importance. The need for periodic
      follow-up under the supervision of the radiation oncologist is stressed and
      illustrated by a clinical case having experienced disastrous consequences.

PMID- 12180035
TI  - [Recommendations for management of acute chest pain. Report of the Belgium
      Interdisciplinary Working Group on Acute Cardiology].
AB  - The Belgium Interdisciplinary Working group on Acute Cardiology, including
      cardiologists, intensivists and urgentists was formed to provide consensus
      regarding the management of acute chest pain in the prehospital and the early
      hospital phase. General recommendations and critical pathways are proposed to
      improve the treatment of the patients with acute coronary syndromes.

PMID- 12180036
TI  - [How I explore ... an orphan metastasis from melanoma].
AB  - A presumed melanoma metastasis is sometimes found without any evidence for the
      primary neoplasm. Such an orphan metastasis merits a complementary exploration.
      Searching for the primary melanoma must then be performed using non invasive and
      clinically oriented methods. Beside a thorough skin examination,
      otorhinolaryngological, ophtalmic and gynecologic searches are recommended. In
      addition, paraclinical investigations are conducted according to the metastatic
      location, the gender and the functional complaints of the patient. The prognosis
      of these orphan metastases is not more dramatic than when the primary lesion is
      identified. Therapies are similar to those proposed in the classical presentation
      of the disease.

PMID- 12180037
TI  - [Pharma-Clinics. Medication of the month. Totelle Cycle: new sequential
      estrogen/progesterone regimen for hormone replacement therapy in menopause].
AB  - Totelle Cycle is a sequential regimen containing 2 mg of oestradiol for 28 days
      associated with a new progestogen, trimegestone, from day 15 to 28. It is
      indicated for the treatment of climacteric symptoms and the prevention of post
      menopausal bone loss. Trimegestone is a new 19-NOR progesterone derivative with
      an original activity profile, near to--but much more powerful than--progesterone
      itself, and devoid of androgenic, glucocorticoid and oestrogenic activity. This
      particular profile confers to trimegestone its metabolic neutrality and concurs
      to the high degree of safety and tolerance observed in studies related to Totelle
      Cycle.

PMID- 12180038
TI  - [Clinical study of the month. Attempt at preservation of B cells during the
      initial phase of type 1 diabetes: negative results with ultralente insulin, but
      promising results with an anti-CD3 monoclonal antibody].
AB  - Type 1 diabetes is an autoimmune disease leading to a progressive exhaustion of
      the insulin secretion and a destruction of the B-cells. Attempts of preservation
      of insulin-producing B-cells can be performed at an early, most often silent,
      stage of the disease in well-selected at high risk subjects or during the period
      immediately following the clinical diagnosis based upon classical signs of
      hyperglycaemia. In the "Diabetes Prevention Trial-Type 1", the prophylactic
      subcutaneous administration of low-dose ultralente insulin was not able to
      prevent the development of type 1 diabetes nor to preserve residual insulin
      secretion in young relatives at very high-risk of diabetes, selected upon
      genetic, immunological and metabolic criteria. In contrast, a pilot randomized
      trial shows that a treatment with a nonactivating humanized monoclonal antibody
      against CD3 mitigates the deterioration in insulin production and improves
      metabolic control, with lower dose of exogenous insulin, during the first year of
      type 1 diabetes mellitus in 9 out of 12 treated patients. Besides a better
      understanding of the natural history of the disease, these clinical trials open
      new perspectives for prevention of type 1 diabetes mellitus, currently assessed
      by the Belgian Diabetes Registry.

PMID- 12180039
TI  - Building the science base for dental public health.

PMID- 12180040
TI  - Orofacial pain: racial and sex differences among older adults.
AB  - OBJECTIVES: This study investigated racial differences in orofacial pain symptoms
      in a sample of older adults. Orofacial pain prevalence, persistence, severity,
      and behavioral impact were assessed. We also tested whether sex and race
      interact, such that racial differences are only observed for a single sex, or
      whether sex differences only occur within a single racial group. METHODS:
      Telephone interviews were conducted with a stratified random sample of 1,636
      community-dwelling older (age 65+ years) north Floridians. RESULTS: Racial
      differences were not found for 12-month prevalence or pain ratings for any
      painful oral symptom, or in the total number of symptoms. The most consistent
      racial differences were in behavioral impact associated with pain. Blacks
      reported greater behavioral impact as defined by pain having reduced their daily
      activities or motivating them to take some action in response to pain. For
      toothache pain, that action was more likely to have been some form of self
      medication. These relationships persisted after controlling for socioeconomic
      status, approach to health care, and pain intensity in multivariable models.
      CONCLUSION: Although pain prevalence is an important public health variable, this
      study suggests that other pain-related variables, such as behavioral impacts, are
      useful when describing disparities associated with orofacial pain.

PMID- 12180041
TI  - Racial and socioeconomic disparities in oral disadvantage, a measure of oral
      health-related quality of life: 24-month incidence.
AB  - OBJECTIVES: This paper estimates the incidence of oral disadvantage based on the
      subject's approach to dental care, sex, race, and financial status; identifies
      demographic and socioeconomic characteristics that were associated with oral
      disadvantage; and determines if these characteristics were differentially
      associated with the three domains of oral disadvantage. METHODS: The Florida
      Dental Care Study was a longitudinal study of oral health in diverse groups of
      persons who at baseline had at least one tooth, were 45 years or older, and were
      either African American or non-Hispanic white. Incidence rates, odds ratios, and
      95 percent confidence intervals were used to describe oral disadvantage and its
      relation to race, income, and other key sociodemographic characteristics.
      RESULTS: The strongest independent predictors of oral disadvantage were approach
      to dental care (problem-oriented attenders or regular), and situation if faced
      with an unexpected $500 dental bill. Demographic and socioeconomic
      characteristics were differentially associated with each disadvantage domain.
      CONCLUSIONS: African Americans, females, rural residents, individuals who did not
      graduate from high school, individuals with limited financial resources, and
      problem-oriented dental attenders had significantly higher occurrences of oral
      disadvantage. Racial and sex disparities in oral disadvantage were largely
      explained by differences in approach to dental care and financial resources
      between these groups.

PMID- 12180042
TI  - Influence of patient, visit, and oral health factors on dental service provision.
AB  - OBJECTIVES: Service provision should reflect the oral health of the patient.
      However, patient and visit factors may influence service patterns and the
      appropriateness of care delivered. The aim of this study was to examine factors
      associated with variation in dental services and to assess whether variation by
      patient and visit characteristics persisted after controlling for oral health
      status. METHODS: A random sample of Australian dentists was surveyed during 1997
      98 (response rate = 60.3%). Private general practitioners (n = 345) provided data
      on service provision, as well as patient, visit and oral health variables from a
      log of a typical clinical day (n = 4,115 patients). Multivariate Poisson
      regression models were run for eight service areas (e.g., diagnostic, preventive,
      and restorative). RESULTS: Significant effects (P < .05) were observed for oral
      health factors in all eight models, visit factors in all eight models, patient
      demographics in four models, dental knowledge/behavior in one model, and area
      based socioeconomic status in one model. CONCLUSIONS: After controlling for oral
      health, visit characteristics persisted as significant predictors of services,
      with nonemergency visits, insurance, and capital city location associated with
      more favorable service mix patterns. Higher socioeconomic status areas and
      payment scale ratings also were associated with a better service pattern in
      particular service areas. These findings show that a wide range of factors, in
      addition to oral health, contribute to variation in service provision.

PMID- 12180043
TI  - The association between Viadent use and oral leukoplakia--results of a matched
      case-control study.
AB  - OBJECTIVES: Several oral pathologists have described oral leukoplakia of the
      maxillary vestibule in patients with no traditional risk factors for the
      condition. On questioning these patients, it was determined that Viadent
      mouthrinse or Viadent toothpaste was commonly used by them. A hypothesis was
      developed that Viadent or a component of Viadent caused the lesions. This paper
      evaluates the association between oral leukoplakia and use of Viadent products.
      METHODS: A matched case-control study was designed to test the hypothesis that
      use of Viadent products increases an individual's risk of oral leukoplakia. Cases
      included 58 patients diagnosed with oral leukoplakia identified through the
      biopsy service at the Ohio State University, College of Dentistry, Oral Pathology
      Section. The matched control was a friend or relative of the patient. Cases and
      controls were administered a questionnaire about their use of Viadent, and other
      known risk factors for leukoplakia such as tobacco and excessive alcohol use.
      RESULTS: An age difference was seen between cases and controls, the cases being
      older (P < .001). After controlling for confounding factors, results of exact
      conditional logistic regression analyses showed that use of Viadent products was
      a risk indicator for oral leukoplakia (odds ratio = 10.0; 95% confidence interval
      = 2.0, 89.2). CONCLUSIONS: Viadent use is a risk indicator for oral leukoplakia,
      confirming our previous findings.

PMID- 12180044
TI  - Comparison of two methods of estimating 48-month tooth loss incidence.
AB  - OBJECTIVES: This paper quantifies validity of self-reported tooth loss, compares
      incidence using two methods (semiannual self-report, biannual clinical
      examination), and compares conclusions about risk factors for tooth loss using
      these two methods. METHODS: The Florida Dental Care Study included persons who at
      baseline had at least one tooth. In-person interviews and clinical examinations
      were conducted at baseline, 24 months, and 48 months, with semiannual telephone
      interviews in between. RESULTS: Agreement between self-reported and clinically
      derived tooth loss was high, although some statistically significant differences
      by certain baseline characteristics were evident. On a nominal scale (some tooth
      loss, none), kappa was 0.88 and percent concordance was 94 percent. On a ratio
      scale, Spearman's correlation was 0.90. Using self-report, the incidence estimate
      would have been 34 percent, as compared to 36 percent based on clinical
      examination. In a single bivariate (loss by self-report, loss by clinical
      examination) multiple logistic regression, conclusions about statistical
      significance and magnitude of seven risk factors for tooth loss did not differ.
      CONCLUSIONS: Validity of self-reported incidence was excellent. The self-reported
      method allowed for semiannual estimates and was less resource intensive.
      Substantive conclusions about tooth loss using either method were similar,
      although validity did differ between persons with certain baseline
      characteristics.

PMID- 12180045
TI  - Integrity of powdered and powder-free latex examination gloves.
AB  - OBJECTIVES: The difference in permeability between one brand of powdered and
      another of powder-free latex examination gloves was evaluated to determine leak
      rates. METHODS: Thirty-one of each type of glove were tested for each of three
      different conditions: usage by dental personnel (1) for 15 minutes or longer, (2)
      for less than 15 minutes, and (3) directly from the manufacturer's packaging
      (zero usage time). Each glove was evaluated in the fingers and the palm. The phiX
      174 viral solution in the glove was allowed to penetrate for 15 minutes. Powder
      (cornstarch) was subsequently added to 20 powder-free gloves, and 15 of these
      were pierced with a 30-gauge needle. RESULTS: Powdered gloves showed no leakage
      rates. Because of this, 30-, 27-, and 25-gauge needles were used to pierce five
      gloves each. One glove with 27- and 25-gauge needle holes showed leakage. Leakage
      rates for powder-free gloves: 45.1 percent for more than 15 minutes of use, 25.8
      percent for less than 15 minutes of use, and 16.1 percent for zero minutes of
      use. Two of the 20 pierced and one of the five unpierced powder-free gloves with
      added cornstarch leaked. CONCLUSION: Significant differences in leak results
      between powdered and powder-free gloves suggest further study is needed.

PMID- 12180046
TI  - Fluctuations in public water fluoride level in Bauru, Brazil.
AB  - OBJECTIVES: The aim of this study was to monitor the quality of public water
      supply fluoridation in Bauru, in the state of Sao Paulo, Brazil. METHODS: Water
      samples collected three times a week during four weeks in 20 areas of
      distribution of water were supplied by the City Water Department of Bauru, Sao
      Paulo, Brazil. Fluoride was analyzed using the ion-specific electrode (Orion
      model 9409) after sample buffering with an equal volume of TISAB II. Data were
      compared to fluoride concentration reported by City Water Department. RESULTS:
      Fluoride content ranged between 0.01 ppm and 9.35 ppm (n = 240). There was great
      variation among the different areas of distribution of water, as showed by the
      Levene test (P < .001). Kruskal-Wallis test showed a statistically significant
      difference in mean fluoride concentration among different areas (P < .001). Mean
      fluoride concentration was less than the optimum concentration (0.8 ppm) in 89
      percent of samples. The values reported by the City water Department were always
      higher than the analyzed fluoride concentrations. CONCLUSIONS: Based on the
      results from this study, more rigorous surveillance and monitoring of water
      fluoridation in Bauru is recommended.

PMID- 12180047
TI  - The epidemiology of self-reported TMJ sounds and pain in young adults in Israel.
AB  - OBJECTIVES: We investigated the prevalence of self-reported temporomandibular
      joint sounds (TMJS), masticatory muscle pain (MMP), and their interrelation in a
      young adult population. METHODS: A large sample (n = 20,869) of young soldiers
      aged 18-21 years who attended dental clinics were asked about their experience of
      TMJ sounds and pain. RESULTS: The overall prevalence of TMJS was 8.4 percent
      (8.9% in females and 8.2% in males) and for masticatory pain was 4.0 percent for
      both males and females (P < .001 under chi-square test). Twenty-five percent of
      patients reporting positive TMJS also reported positive MMP compared to 2 percent
      in the negative TMJS group (P < .001). Fifty-three percent of patients reporting
      positive MMP also reported positive TMJS, compared to 6.5 percent in the negative
      MMP group (P < .001). CONCLUSIONS: The low prevalence of TMJ sounds and pain
      found in these study might be attributed to the different cultural and social
      environment, as well as to the uniformity in age of the study group.

PMID- 12180048
TI  - The John W. Knutson Distinguished Service Award in Dental Public Health--2001
      recipient Robert E. Mecklenburg.

PMID- 12180049
TI  - Remarks on receiving the John W. Knutson Distinguished Service Award.

PMID- 12180050
TI  - [Kidney cancer metastasis to the adrenal gland. Role of adrenalectomy].
AB  - We analysed case records of 2507 patients with renal cell carcinoma treated in
      the department of onco-urology of Cancer Research Center (Moscow). 1939 of them
      underwent nephrectomy between 1971 and 1999. The overall incidence of adrenal
      metastases according to CT and histological findings was 4.7%. Synchronous
      metastases occurred in 90 and metachronous ones in 30 patients. Radical
      nephrectomy with adrenalectomy was performed in 18 out of 90 patients with
      synchronous metastases, palliative nephrectomy in 20 and 52 patients were not
      considered for surgery. Among 18 patients who underwent complete surgical
      resection, 12(66%) had either lymph node involvement or distant metastases. A
      microscopic metastasis was found on histological examination only in 1 patient
      with normal CT scan and macroscopically intact adrenal on intraoperative
      assessment. Mean survival after radical nephrectomy with adrenalectomy in 6
      patients with solitary lesions was 57 months compared to the longest survival of
      31 months in patients with widespread disease. Solitary metachronous ipsilateral
      and contralateral adrenal involvement was present in 7 patients. The average
      interval between nephrectomy and appearance of adrenal metastasis in this group
      was 73 months. One patient was lost for follow-up and one died of adrenal
      deficiency 4.3 months after adrenalectomy. One patient underwent a consecutive
      removal of brain and lung metastases 33 and 38 months following adrenalectomy
      while the remaining 4 were alive in 15, 16, 26 and 34 months with no evidence of
      the disease. Thus, ipsilateral adrenalectomy is obligatory only in patients with
      severe disease as shown by CT scan or at nephrectomy. About one-third of the
      patients will benefit from the surgery. Adrenalectomy should be performed in case
      of obvious adrenal involvement. The aggressive surgical approach is justified in
      solitary metachronous adrenal involvement because of long-term survival expected
      in some of such patients.

PMID- 12180051
TI  - [Treatment of benign prostatic hypertrophy with prostaplant].

PMID- 12180052
TI  - [Bacteriostatic shock in acute purulent pyelonephritis].
AB  - Fifty-seven patients with acute purulent pyelonephritis (APP) complicated by
      bacteriotoxic shock (BTS) were treated in Daghestan Medical Academy's urological
      clinic from 1982 to 1999. The condition was primarily caused by acute occlusion
      of the urinary tracts. The first step of the treatment was aimed at the recovery
      of normal hemodynamics. As early as the first hours of BTS, plasma- and
      hemosorption, hemodialysis, hemodialysis were made. If the patients got better,
      they were operated to remove the obstruction for urine flow (epicystostomy,
      nephrostomy). 28 recent cases received adjuvant laser therapy--irradiation of the
      cavitary renal system and blood. This was performed via light guide inserted into
      the renal pelvis through the nephrostomic drainage. The guide was connected with
      the He-Ne optic quantum generator AFL-1. Laser procedure lasted for 8-12 min, a
      course consisted of 7-8 procedures. Later, laser beam was also directed to the
      biologically active points corresponding to pyelonephritis. Normalization of
      renal function and T, B immunity was faster in patients exposed to laser
      radiation. Lethality in this group was lower.

PMID- 12180053
TI  - [Effectiveness of imipenem/cilastatin (Tienam, MSD) in treating complicated
      infections in urology].
AB  - Complicated urinary infections tend to eventuate in severe pyoseptic
      complications--bacteriuria, sepsis. The search for methods of fighting agents of
      urinary infections goes in the direction of perfection of already existing
      methods and in the direction of design of novel antibacterial drugs. In the
      middle 1980s the first carbapenem drug-imipenem--was proposed for urological
      clinical practice. Mechanism of its action as that of the other beta-lactam
      antibiotics consists in impairment of synthesis of bacterial cell wall as a
      result of the drug penetration through the surface membrane and irreversible
      binding with penicillin-binding proteins. Imipenem is active against most gram
      positive and gram-negative aerobic and anaerobic microorganisms which cause
      severe urological infections. The article presents the results of treatment of 45
      patients with severe urological infections with multiple resistance of the
      causing agent and failure of previous treatment. Imipenem was given in a daily
      dose 1.5-2.0 g. Sometimes a stepwise regimen was used: 500 mg 4 times a day
      intravenously for the first 3-4 days, then 500 mg twice a day intramuscularly for
      the following 3-4 days. In detection of highly sensitive bacteria (E. coli,
      Proteus mirabilis) daily doses were reduced to 1 g. In long standing infection
      caused by Pseudomonas aeruginosa imipenem was combined with amicacin. In high
      surgical risk of postoperative period imipenem was given prior to surgery and
      continued after it for 5 to 14 days. Good therapeutic results were achieved:
      clinical effect reached 95.5%, antibacterial efficiency was 87.8%. Thus, imipenem
      is antibiotic of the first line in empirical therapy of severe bacterial
      infections in urology as it has a wide spectrum of antibacterial action. We
      believe that this drug should not be left as a reserve but used for a starting
      empirical therapy of severe infections in urological hospital.

PMID- 12180054
TI  - [Dynamics of immunologic and biologic indicators in laser therapy on patients
      with acute pyelonephritis].

PMID- 12180055
TI  - [Increase in structural-functional tolerance of kidney to ischemia upon
      parenteral administration of sodium hypochlorite in the pre-ischemic period].
AB  - The opportunity of raising kidney structural and functional tolerance to ischemia
      with parenteral injections of 0.06% solution of sodium hypochlorite for 4 days in
      preischemia period was studied in experiment on 22 non-inbred rats of 200-280 g
      body weight. 90 minute ischemia was created by ligating the left and right kidney
      arteries, veins, ureters. Morphological and functional kidney data, enzymuria
      activity of nephron epithelium cells were registered, 80 and 33% of the rats
      survived 7 days after ischemia in the study and control groups, respectively. The
      control animals showed deterioration of the tubules function, high enzymuria.
      Thus, it is possible to raise kidney tolerance to ischemia by preischemic
      parenteral injection of sodium hypochlorite solution.

PMID- 12180057
TI  - [Results of clinical use of the polyfunctional lithotripsy device "Dornier-U
      50"].
AB  - The review of the results of clinical application of a polyfunctional
      lithotriptor Dornier-U50 in urolithiasis patients is presented. The treatment of
      324 patients produced good results of lithotripsy in uroliths of any location in
      generating high-energy shock waves. Complete fragmentation was achieved in 86.4%,
      partial one--in 11.7%. Complications occurred in 9% of which 5.3% were cases of
      upper urinary obstruction. The Dornier-U50 lithotriptor can be used for both
      extracorporeal lithotripsy (under x-ray and ultrasound targeting) and various
      endoscopic operations under x-ray telecontrol. This allows maximal utilization
      efficiency of this equipment in diagnosis and treatment in urological hospitals.

PMID- 12180058
TI  - [Extracorporeal shock wave lithotripsy and recurrent urolithiasis].
AB  - Changes in concentrations of total thyroxine (T4) and triiodothyronine (T3) in
      blood plasma, blood coagulation and prothrombin index (PI) 9 days after exposure
      to extracorporeal shock-wave lithotripsy (ESWL) were studied in patients with
      urolithiasis. Urolithiasis patients with chronic pyelonephritis running with non
      severe renal pain had often elevated concentrations of T3, T4 and blood
      coagulation. On day 9 after ESWL plasma concentration of T3 and coagulation
      decreased while T4 concentration and PI rose. The analysis of 4-year follow-up
      after ESWL demonstrates that high levels of T4 and PI on day 9 after ESWL may
      contribute to development of recurrent urolithiasis.

PMID- 12180056
TI  - [Results of organ-preserving therapy for invasive bladder cancer].
AB  - 87 patients with urinary bladder cancer (UBC) stage T2-3aN0M0 have received an
      organ-saving treatment which combined neoadjuvant chemotherapy (methotrexate,
      adriamycin, vinblastin, cysplatinum) followed by transurethral or open resection
      of the bladder. The patients were followed up for 3 to 60 months. Recurrent
      tumors arose in 49(56.3%) patients, at the primary site in 94%. Recurrence-free 5
      year survival made up 32.8 +/- 14.1 and 24.2 +/- 15.2% after transurethral and
      open resections of the bladder, respectively. In patients with a complete
      response to the neoadjuvant chemotherapy 5-year overall and recurrence-free
      survival reached 89.0 +/- 11.1 and 68.5 +/- 18.9%, respectively. It is thought
      valid to consider planning organ-saving treatment only in relation to patients
      with a complete regression of the tumor after neoadjuvant chemotherapy.

PMID- 12180059
TI  - [Sildenafil and alprostadil in the combined drug therapy of erectile
      dysfunction].
AB  - Forty-four patients with erectile dysfunction (ED) aged 21-72 years aged 21-72
      years (mean age 61 years) were examined and treated with sildenafil and
      alprostadil monotherapy or combined therapy. ED was psychogenic in 9(20.5%),
      arterial in 12(27.2%), vein occlusive in 9(20.5%) and neurogenic in 14(31.8%)
      patients. Monotherapy was most effective in psychogenic ED (alprostadil--100%,
      sildenafil--88.9%), least effective in vein occlusive ED (alprostadil--33.3%,
      sildenafil--22.2%). Alprostadil was more effective in arterial and neurogenic ED
      (83.3 vs 66.7 and 78.6 vs 57.1%, respectively). Combination of the two drugs
      produced much high response: 100, 85.7 and 55.5% in arterial, neurogenic and vein
      occlusive ED, respectively. Thus, combined treatment with sildenafil and
      alprostadil is a method of choice in the treatment of ED in failure of
      monotherapy with these drugs or in vein occlusive ED. In the combined treatment
      dose of the drugs, number of side effects and cost of therapy are lower.

PMID- 12180060
TI  - [Principle of hydronephrosis and choice of surgical method].
AB  - Experience in operative treatment of 1574 patients suffering from hydronephrosis
      is analysed. Among them, 656 patients were operated in the Chernobyl zone.
      Radical surgery, palliative operations and nephrectomy were performed in 63, 21.5
      and 16.5% patients, respectively. According to operative
      electropyeloureterography and histological examination of the removed material,
      circulatory segmental hypoplasia of near pelvis ureter in hydronephrosis had
      decreased electric potentials, up to their absence, urodynamic disorders.
      Ureteral hypoplasia is often associated with high branching of the ureter,
      additional aberrant renal vessel. In functional hydronephrosis it may be a
      primary cause of hydronephrosis and influence the choice of the operative
      treatment. Postoperative course of hydronephrosis in the Chernobyl zone is
      characterized by more frequent complications because of subnormal immunity and
      high virulence of urinary infection. For 12 years after the Chernobyl accident,
      no direct effects of low-dose radiation on renal function is ascertained. Renal
      function after radical plastic operations depended on the disease severity. In
      the Chernobyl zone all kinds of radical plastic operations in hydronephrosis were
      performed.

PMID- 12180061
TI  - [Postoperative cystitis in children].
AB  - Operative intervention on the urinary bladder in children entails postoperative
      reactive cystitis. Biopsies of urinary bladder mucosa were studied
      morphologically. Basing on these morphological findings and clinical evidence,
      three leading variants of the mucosa changes were distinguished: focal squamous
      cell metaplasia; excess of the lymphoid tissue and lymphangiectasia;
      hemangiectasia. These morphological changes aggravate the course of postoperative
      cystitis. UHF-therapy and magnetic-laser radiation beginning postoperative day 4
      and 7, respectively, reduce inflammation developing in postoperative cystitis.
      This indicates effectiveness of the above combined therapy which can be also used
      for prevention of acute inflammation episodes in postoperative period.

PMID- 12180062
TI  - [Modes of intensive therapy for arterial hypertension in children with terminal
      chronic kidney failure].
AB  - In spite of considerable progress in development of pediatric science, intensive
      therapy of kidney diseases remains the pressing issue because of high lethality
      among patients with renal failure (RF). Cardiovascular diseases, especially
      malignant hypertension syndrome with development of left ventricular
      insufficiency, are leading among the causes of late deaths of postdialysis
      patients. We studied hemodynamics in 18 children with terminal chronic renal
      failure running with marked arterial hypertension and left ventricular
      hypertrophy. We have found that high blood pressure was initially caused by
      hyperhydration and hypernatriemia. After hemodialysis, children with KT/V > 1
      developed hypertension due to hyperkinetic hemodynamics. Establishment of "dry
      weight" of the child on programmed dialysis was followed by renin-dependent
      arterial hypertension which was treated by inhibitors of angiotensin-converting
      enzyme and calcium antagonists, in one case by nephrectomy. In hemodialysis
      regimen KT/V < 1, dry weight was not achieved and hyperhydration-caused
      hypertension remained. Moderate arterial hypertension due to cukinetic
      hemodynamics was achieved only after 4 weeks of hemodialysis in administration of
      calcium antagonists, beta-blockers and central sympatholytics.

PMID- 12180063
TI  - [Iatrogenic foreign body].
AB  - Three cases of iatrogenic foreign bodies are described. In case 1 a large stone
      was removed from the urinary bladder of a 80-year-old man 8 years after
      suprapubic prostatectomy. The concrement contained a fragment of the gauze tampon
      left during that operation. In case 2 a surgeon trying to stop a profuse
      hemorrhage lost a surgical needle in paraurethral tissues above the urinary
      bladder of an elderly man undergoing prostatectomy. Because of the foreign body
      the patient developed complications: scarry obliteration of the bladder neck,
      concrement, a vesical fistula, chronic cystitis and chronic pyelonephritis. In
      case 3, the Dormia's basket broke with ureteral perforation and the metal
      fragments penetrated into the paraureteral fat in a 46-year-old woman undergoing
      ureterolithoextraction. 11 months later, the fragment migrated into the bladder
      wall and perforated it. The fragment was removed endoscopically.

PMID- 12180065
TI  - [Diverticulum of the urinary bladder].

PMID- 12180064
TI  - [Hydatid echinococcosis of paravesicular cellular tissue, simulating hydrocele].
AB  - A rare case of echinococcus granulosus echinococcosis of the paravesical fat
      simulating hydrocele is reported. After ideal echinococcectomy the patient was
      discharged with cure.

PMID- 12180066
TI  - [Modern methods of treating urethral strictures].

PMID- 12180067
TI  - [Comparative evaluation of the quality of life in patients with kidney cancer
      after organ-preserving operations and radical nephrectomy].
AB  - The study included 26 patients with renal carcinoma (RC) stage T1 which have
      undergone elective conservative surgery and 33 patients with the same disease
      after radical nephrectomy. To compare their postoperative quality of life, the
      patients filled in questionnaire EORTC QLQ-C30 (version 3) for cancer patients.
      The results of the questionnaire survey show a higher quality of life in RC
      patients after organ-saving operations, i.e. their physical condition is better,
      social adaptation faster. High quality of life and good 5-year survival suggest
      that conservative elective surgery in renal carcinoma stage T1 is an alternative
      to radical nephrectomy.

PMID- 12180068
TI  - [Decisions of the plenary meeting of the board of the Society of Urology
      (Yaroslavl'. 21-24 May 2001)].

PMID- 12180069
TI  - [Differential-diagnostic value of changes in nuclear ploidy of prostate
      epithelial cells during the carcinogenesis process].
AB  - Ploidometry of prostatic cell nuclei at different stages of carcinogenesis was
      made in 80 patients using 8 mcm histological sections stained by Felgen. Ploidy
      of 1332 nuclei of prostatic epithelial cells and 396 lymphocytes (tissue ploidy
      standard) was studied on computer image analyser "Imager-CG (computer program
      version Avtan-San). The study covered interphasic nuclei of the cells of the
      germinative zones of normal and hyperplastic structures, areas of intraepithelial
      neoplasia and adenocarcinoma with various disdifferentiation degree. Significant
      differences in ploidy and proliferative activity of prostatic cells at different
      carcinogenesis stages were revealed. Ploidometry data may help to take decision
      in differential histopathological diagnosis of benign and malignant tumors of the
      prostate.

PMID- 12180070
TI  - Spectrum of MECP2 mutations in Rett syndrome.
AB  - Mutations in the MECP2 (Methyl-CpG-binding protein) gene recently have been
      reported to cause Rett syndrome (RTT), an X-linked progressive encephalopathy. We
      have collected the results of MECP2 analysis conducted in four laboratories in
      France. A total of 301 RTT alleles have been analyzed, demonstrating a total of
      69 different mutations so far observed and accounting for 64% of MECP2 genes in
      RTT patients living in France. R168X (11.5%) is the most common of MECP2
      mutations, followed by R255X (10.9%), R270X (10.5%), T158M (7.8%), and R306C
      (6.8%). Only 10 mutations had a relative frequency > 2%. A total of 59 mutations
      were found in a small number of RTT alleles (from 1 to 2). These data demonstrate
      the high allelic heterogeneity of RTT in France and provide information relevant
      to the development of strategies for molecular diagnosis and genetic counseling
      in RTT families.

PMID- 12180071
TI  - Familial Mediterranean fever (FMF) mutations occur frequently in the Greek
      Cypriot population of Cyprus.
AB  - Familial Mediterranean Fever (FMF) is an autosomal recessive disease of high
      prevalence within Mediterranean countries and particularly common in four ethnic
      populations: Arabs, non-Ashkenazi Jews, Armenians, and Turks. The responsible
      gene MEFV has been assigned to chromosome 16p13.3. Our aim was to establish the
      frequencies of the most common mutations in Greek-Cypriots. We found that 1 in 25
      is a carrier of one of three mutations. V726A, M694V, and F479L. In 68 Grek
      Cypriot FMF chromosomes analyzed, we found V726A (25%), F479L (20.6%), M694V
      (17.6%), and others (36.8%). Mutation F479L, relatively common in this
      population, is very rare elsewhere. Our study indicates that FMF is not a rare
      condition in Cyprus and that, because of the significant morbidity associated
      with this disorder, which is often diagnosed only after unnecessary surgeries, a
      newborn screening program to detect affected in this population may be warranted.

PMID- 12180072
TI  - A proposed role for consumers and the general public as consumers of health care
      in community-wide genetic testing.

PMID- 12180073
TI  - Perceptions of genetics research as harmful to society: differences among samples
      of African-Americans and European-Americans.
AB  - Genetics has the potential not only to find cures for diseases, but to possess
      the mechanisms to change the bio-social make-up of populations. A specific
      question that has arisen on this issue is how developments in genetic technology
      may intersect with existing race and ethnic relations. Evidence of the
      racialization of some genetic disorders has been demonstrated elsewhere. The
      purpose of this study is to compare and contrast African-American and European
      American attitudes on the benefits of genetics research for society. Findings
      show that African-Americans were more likely to say genetics research is harmful
      for society. This relationship remained statistically significant after controls
      were introduced in a regression model. Demographic characteristics and self-rated
      knowledge of genetics had no effect on attitudes among African-Americans. A
      willingness to use genetic services correlated with favorable attitudes.
      Differences in social position may lead some groups to opposing interpretations
      and symbolic meanings of genetics. This may be true in the context of this study
      because the social meanings of genetics may be tainted by racialization,
      historical attempts at eugenics, and the potential abuse of genetics targeting
      groups partially defined by superficial genetic characteristics.

PMID- 12180074
TI  - Addressing consumer grievances in medicine: policies and practices of newborn
      screening programs in the United States.
AB  - Newborn screening programs collectively administer the largest genetic testing
      initiative in the United States. The redress of grievances is an important
      mechanism for consumers to provide input into clinical and public health
      programs. In this study, we evaluated mechanisms for addressing consumer
      grievances in newborn screening programs. To do this, we surveyed all 50 state
      plus the District of Columbia newborn screening programs by questionnaire
      regarding protocols for receipt and redress of problems reported by parents of
      newborns and ascertained the existence and nature of complaints and how
      complaints were documented and addressed. Pertinent state and federal legislation
      and regulation were also reviewed. Six of 49 newborn screening programs reported
      having formal policies for handling consumer grievances. Four states reported
      having pertinent legislation or regulation. Thirty-eight of 49 states reported
      having received complaints from 1993 to 1995. Thirteen of 49 newborn screening
      programs reported that they actively seek feedback from consumers. Consumer
      grievances ranged from minor complaints to potentially life-threatening concerns.
      In general, complaints are managed on an ad hoc basis; formal policies are
      typically lacking. As newborn screening programs affect a vast number of
      Americans, a proactive and comprehensive approach, including solicitation of
      consumer feedback, could benefit both newborn screening programs and the public
      served by them.

PMID- 12180075
TI  - Health-related quality-of-life assessment of prenatal diagnosis: chorionic villi
      sampling and amniocentesis.
AB  - This study assesses the health-related quality-of-life (HRQL) effects of
      chorionic villi sampling (CVS) and genetic amniocentesis (GA), including both
      process and outcomes of prenatal diagnosis. The HRQL of 126 women participating
      in a randomized controlled clinical trial of CVS versus GA in Toronto and
      Hamilton, Ontario, was assessed in four interviews at weeks 8, 13, 18, and 22 of
      pregnancy. Statistical analyses included analysis of variance, repeated measures
      analysis of covariance, chi-square, Fisher's exact test, Student's t-tests, and
      paired t-tests. Utility scores for patients undergoing CVS exceeded those for GA
      patients at week 18 (p = 0.04). Utility scores for hypothetical health states did
      not differ significantly by trial arm. CVS results in slightly improved HRQL
      during prenatal diagnosis. This advantage needs to be weighed against the high
      disutility patients attach to infrequent outcomes associated with pregnancy
      losses, equivocal diagnoses, and diagnostic inaccuracy.

PMID- 12180076
TI  - Does prenatal screening for 5,10-methylenetetrahydrofolate reductase (MTHFR)
      mutations in high-risk neural tube defect pregnancies make sense?
AB  - Despite the fact that neural tube defects (NTDs) are the most common congenital
      malformations of the central nervous system, investigators have yet to identify
      responsible gene(s). Research efforts have been productive in the identification
      of environmental factors, such as periconceptional folic acid supplementation,
      that modulate risk for the development of NTDs. Studies of the folic acid
      biosynthetic pathway led to the discovery of an association between elevated
      levels of homocysteine and NTD risk. Researchers subsequently identified single
      nucleotide polymorphisms in the gene coding for the enzyme 5,10
      methylenetetrahydrofolate reductase (MTHFR). Association studies suggested it was
      a potential risk factor for NTDs, because the thermolabile form of the enzyme led
      to elevated homocysteine concentrations when folic acid intake is low. Numerous
      studies analyzing MTHFR variants have resulted in positive associations with
      increased NTD risk only in certain populations, suggesting that these variants
      are not large contributors to the etiology of NTDs. With our limited
      understanding of the genes involved in regulating NTD susceptibility, the paucity
      of data on how folic acid protects the developing embryo, as well as the observed
      decrease in birth prevalence of NTDs following folic acid supplementation and
      food fortification, it makes little sense for prospective parents to be tested
      for MTHFR variants, or for variants of other known folate pathway genes.

PMID- 12180077
TI  - Detection of the G-->T polymorphism at the Sp1 binding site of the collagen type
      I alpha 1 gene by a novel ARMS-PCR method.
AB  - The G-->T mutation at base 1 of intron 1 at the binding site of the Sp1
      transcription factor of the collagen type I alpha 1 gene (COLIA1, GenBank
      accession no. AF017178) is a putative marker for low bone mineral density and
      osteoporotic fractures. A new method for the detection of this mutation is
      presented, based on the amplification refractory mutation system-polymerase chain
      reaction (ARMS-PCR), which utilizes two separate and simultaneous PCRs to detect
      the normal and mutated alleles. The forward primer (positions 1307-1336 of the
      gene) is common to both amplifications. Two reverse primers (positions 1566-1546)
      are used, differing in the 3' base (3'-C for the normal S allele and 3'-A for the
      mutated s allele). The former amplification uses the reverse primer specific for
      the S allele; the latter uses the reverse primer with the 3'-base complementary
      to the mutated base of the s allele. In the SS condition, amplification occurs
      only in the former reaction and in the ss condition only in the latter. Both
      reactions give a product in the Ss condition. Direct DNA sequencing of a COLIA1
      region containing the G-->T polymorphism demonstrates the validity of this ARMS
      PCR method. The new method is more reliable than a previously published detection
      method, which utilizes a mismatched reverse primer, introducing a restriction
      site in the T-substituted (s) allele. However, the restriction enzyme is costly,
      its digestion time long, and incomplete digestion can lead to an underestimation
      of the frequency of ss homozygosity. The latter can result in incorrect
      conclusions about a linkage between osteoporosis and the COLIA1 polymorphism. In
      a survey of the COLIA1 polymorphism in 133 osteoporotic subjects with femur
      fractures, 7 cases of ss homozygosity were consistently detected both by direct
      DNA sequencing and by the ARMS-PCR method. This, in contradistinction to the
      mismatched-primer method by which 3 of these 7 cases were inaccurately diagnosed
      as Ss heterozygosities.

PMID- 12180078
TI  - Hereditary hemochromatosis: the clinical significance of the S65C mutation.
AB  - Hereditary hemochromatosis (HH) is a common genetic disease with iron overload in
      certain organs, especially the liver. Most cases are homozygous for the C282Y
      mutation in the HFE gene; a few are C282Y heterozygous, compound C282Y/H63D
      heterozygous, or have no known mutation. A third mutation, S65C, has been
      associated with HH, but this finding is disputed. We have studied the clinical
      significance of various genotypes with the S65C mutation. In a population-based
      screening for HH in 65,238 persons, 613 had high serum transferrin saturation in
      two blood samples and were invited for HFE genotyping. In 556 persons with
      complete data sets, we studied the serum ferritin concentration and the risk of
      being diagnosed with phenotypic HH in the various genotypic groups. The
      phenotypic diagnosis was given without knowing the genotypic result. Except for
      the C282Y homozygotes, no differences in median serum ferritin concentrations
      were found between the various genotypic groups. However, the C282Y/S65C compound
      heterozygous group had a higher risk of being diagnosed with phenotypic HH than
      the wild-type group, as did the C282Y homozygous and the C282Y/H63D compound
      heterozygous groups. When combined with the C282Y mutation, the S65C mutation is
      associated with an increased risk of being diagnosed with phenotypic HH.

PMID- 12180079
TI  - T594M mutation of the beta-subunit of the epithelial sodium channel in Ghanaian
      populations from Kumasi and London and a possible association with hypertension.
AB  - We have tested 186 individuals from Ghana, 95 indigenous and 91 who have settled
      in the United Kingdom, for the presence of the T594M mutation in the beta-subunit
      of the epithelial sodium channel, which is associated with hypertension in black
      populations. The group living in Ghana had a mean age of 27 years and were
      normotensive, but had an increased frequency of the T allele compared to the
      London-based population. If this is reflected in larger studies, and the link
      with hypertension is maintained in the Ghanaian population, this mutation could
      be a significant cause of hypertension in Ghana.

PMID- 12180080
TI  - An improved assay for genotyping the common Alu insertion in the tissue-type
      plasminogen activation gene PLAT.
AB  - An improved assay for genotyping the common Alu insertion in the tissue-type
      plasminogen activator (PLAT) locus is described in this report. The assay is a
      valuable asset to clinical researchers interested in exploring disease
      associations with this allele. The automation and improved accuracy will
      facilitate future population-based studies, as well as clinical screening.

PMID- 12180081
TI  - Diagnostic DNA testing for X-linked ocular albinism (OA1) with a hierarchical
      mutation screening protocol.
AB  - Albinism is a group of inherited conditions in which affected individuals have
      less than normal pigment in the eyes, skin, and hair compared to others of the
      same race and ethnic background. The prevalence of all types of albinism in the
      United States is estimated at 1 in 20,000, based on poor epidemiological data. X
      linked Nettleship-Falls ocular albinism (XLOA, OA1) affects approximately
      1/150,000 males in the population. XLOA effects reduce visual acuity and
      nystagmus, result in a mild skin and hair phenotype, and occur mostly in XY
      males. Female carriers of XLOA have normal visual acuity, but often show iris
      punctate transillumination and a classic pattern of mosaic retinal pigmentation,
      coarse and grainy in the macula and becoming increasingly reticular into the
      periphery of the retinal pigment epithelium. Studies of OA1 have shown linkage of
      a single gene to markers at Xp22.3-p22.2. About 48% of the reported mutations in
      the OA1 gene are intragenic deletions and about 43% are point mutations. We
      present a hierarchical strategy for mutation screening for diagnostic testing for
      OA1 that comprises two tiers: first, multiplex PCR to detect intragenic deletions
      in the OA1 gene with denaturing high-performance liquid chromatography (dHPLC),
      and, second, heteroduplex analysis with dHPLC to scan for mutations, with
      subsequent sequencing of variants to confirm putative mutations in the OA1 gene.
      Prenatal diagnosis can be provided for families when the mutation has been firmly
      identified. We have validated this procedure with positive controls that were
      identified in patients by Southern blot, single-stranded conformation
      polymorphism (SSCP), and sequencing. In this hierarchical strategy, these
      procedures have an analytical sensitivity of > 99%.

PMID- 12180082
TI  - Genetic differentiation among host-associated Alebra leafhoppers (Hemiptera:
      Cicadellidae).
AB  - The limited importance ascribed to sympatric speciation processes via host race
      formation is partially due to the few cases of host races that have been reported
      among host populations. This work sheds light on the taxonomy of Alebra
      leafhoppers and examines the possible existence of host races among host
      associated populations. The species of this genus show varying degrees of host
      association with deciduous trees and shrubs and, frequently, host populations of
      uncertain taxonomic status coexist and occasionally become pests. Allozyme
      electrophoresis of 21 Greek populations including sympatric, local and
      geographically distant samples collected on 13 different plant species, show that
      they represent at least five species: A. albostriella Fallen, A. viridis (Rey)
      (sensu Gillham), A. wahlbergi Boheman and two new species. Of these, one is
      associated to Quercus frainetto and other is specific to Crataegus spp.
      Significant genetic differences among sympatric and local host populations were
      found only in A. albostriella, between populations on Turkey oak, beech and
      common alder. It is suggested that the last two of these host populations may
      represent different host races. The results show that both the host plant and
      geographical distance affect the patterns of differentiation in the genus. The
      formation of some species seems to have been the result of allopatric speciation
      events while, for others, their origin can be equally explained either by
      sympatric or allopatric speciation.

PMID- 12180083
TI  - On the use of double haploids for detecting QTL in outbred populations.
AB  - The power to detect quantitative trait loci (QTL) using the double haploid (DH),
      full-sib (FS) and hierarchical (HI) designs implemented in outbred fish
      populations was assessed for interval mapping using deterministic methods. The
      predictions were tested using simulation. The DH design was most efficient for
      the range of designs and parameters considered and was most beneficial when the
      FS design was not very powerful. The difference between the design was largest
      for a low amount of residual genetic variation. Accounting for an increase of the
      environmental variance due to the genetic constitution of the double haploid
      progeny changed the magnitude of the power, but the ranking of the designs
      remained the same. As large full sib family sizes can be obtained in fish, the
      practical value of HI designs as a strategy for increasing the power of QTL
      mapping experiments is limited when compared with the FS design. Overall, the
      results suggested that the DH design could be a very useful tool for QTL mapping
      in fish, and of particular importance when the effect of the QTL is low and the
      residual genetic variation from other chromosomes can be controlled by using
      multiple markers.

PMID- 12180084
TI  - The effects of altitude, aspect, grazing and time on the proportion of
      cyanogenics in neighbouring populations of Trifolium repens L. (white clover).
AB  - The proportion of cyanogenic individuals of white clover amongst 200 individuals
      in each of 32 neighbouring populations in Northumberland, UK were recorded. Sites
      differed for four altitude zones, two aspects, and were either sheep pasture or
      ungrazed meadow. The proportion of cyanogenics showed a striking reduction with
      increasing altitude. Below 100 m, north-facing sites contained more cyanogenics
      than south-facing sites, but aspect did not affect higher sites. Grassland
      management had no effect on the proportion of cyanogenics. A 24-year study of one
      population showed highly significant changes in the proportion of cyanogenics
      over time, suggesting that a significant turnover of individuals occurs. In some
      cases, different size class cohorts varied for the proportion of cyanogenics
      within a year, and the same cohort varied between years. We conclude that
      environment at birth may determine the proportion of cyanogenics for that cohort,
      so that this proportion persists in that cohort as it matures. Comparisons of the
      proportion of cyanogenics with mean monthly averages for January minimum
      temperature, July maximum temperature and August rainfall showed a significant
      association only with mean January minima 2 1/2 years previously. We hypothesise
      that the 2 to 3-year cohort may predominate in this population. We suggest that
      winter cold and summer drought may both select against cyanogenics. Grazing by
      large herbivores does not favour cyanogenesis, but some invertebrate herbivory
      may do so. Most selection probably occurs at birth and will be greatest in
      populations with a high turnover.

PMID- 12180085
TI  - Inheritance of an oviposition behavior by an egg parasitoid.
AB  - A quantitative genetic study revealed genetic and environmental sources of
      variance in percentage parasitism of European corn borer egg masses and secondary
      sex ratios by Trichogramma nubilale. Full and half-sib groups of T. nubilale were
      obtained from a nested mating design, which permitted the partitioning of the
      variance of T. nubilale parasitism of European corn borer egg masses into
      additive genetic variance, maternal/dominant variance and environmental variance.
      A mother-daughter regression of the percentage of an egg mass parasitized allowed
      a determination of the direction of a potential response to selection in the
      event of maternal effects. No or very little additive genetic effects were
      associated with the percentage of eggs within a mass parasitized and secondary
      sex ratios, but a significant amount of the variance for both traits had a
      maternal and/or dominant genetic source. The relationship between mothers and
      daughters in egg mass parasitism was positive, and 55.4% of the progeny of a
      given mother had behaviors that resemble their mother. Most of the variance had
      an environmental and/or unknown genetic source implying potentially high
      phenotypic plasticity associated with all these traits. The presence of maternal
      effects and phenotypic plasticity could have multiple and complex effects on
      progeny characters and potential responses to selection.

PMID- 12180086
TI  - Feminizing Wolbachia in an insect, Ostrinia furnacalis (Lepidoptera: Crambidae).
AB  - Wolbachia, which forms a group of maternally inherited bacteria in arthropods,
      often cause reproduction alterations in their hosts, such as cytoplasmic
      incompatibility, parthenogenesis, male-killing, hybrid breakdown and
      feminization. To date, Wolbachia-induced feminization has been reported only in
      isopods. Here we report that a Wolbachia strain feminizes an insect host,
      Ostrinia furnacalis. Among 79 wild females of O. furnacalis examined, Wolbachia
      infection was detected in 13 females. Twelve of the 13 infected females produced
      all-female progenies, and this trait was maternally inherited. Tetracycline
      treatment of thelygenic matrilines resulted in the production of all-male
      progenies. The present findings indicate that the Wolbachia infection induces
      feminization of genetic males in O. furnacalis. Differences in the Wolbachia
      induced feminization in O. furnacalis and that in isopods are discussed along
      with the differences in sex determination mechanisms between insects and isopods.
      Phylogenetic analysis of the wsp gene sequence of Wolbachia suggests independent
      evolutionary origins for the Wolbachia-induced feminizations in O. furnacalis and
      in isopods. Our findings over 5 years suggest that the infection has been
      maintained at a low prevalence in the O. furnacalis population.

PMID- 12180087
TI  - The maize Brown midrib1 locus affects cell wall composition and plant development
      in a dose-dependent manner.
AB  - The four brown midrib (bm) mutants of maize have a reduced content and altered
      subunit composition of the cell wall polymer lignin. The bm mutations have
      traditionally been considered completely recessive, because the brown midrib
      phenotype is only apparent in plants homozygous for the mutation. In addition to
      an effect on cell wall composition, some bm mutations have been shown to affect
      flowering time. We had preliminary evidence for a dosage effect of the Bm1 locus
      on flowering time, which prompted this detailed study on the Bm1 locus. In this
      study, near-isogenic lines (in an A619 background) with zero, one or two bm1
      mutant alleles were compared. The bm1 heterozygotes flowered significantly
      earlier than both the wild-type plants and bm1 mutants. This difference can at
      least be partly attributed to an accelerated growth rate in the later stages of
      plant development. Furthermore, Fourier transform infrared spectroscopy revealed
      that the cell wall composition of the bm1 heterozygous plants is distinct from
      both the bm1 and wild-type homozygotes. The combination of the data on flowering
      time and the data on cell wall composition provide evidence for a dosage effect
      at the Bm1 locus.

PMID- 12180088
TI  - S-allele diversity in Sorbus aucuparia and Crataegus monogyna (Rosaceae:
      Maloideae).
AB  - RT-PCR was used to obtain the first estimates from natural populations of allelic
      diversity at the RNase-based gametophytic self-incompatibility locus in the
      Rosaceae. A total of 20 alleles were retrieved from 20 Sorbus aucuparia
      individuals, whereas 17 alleles were found in 13 Crataegus monogyna samples.
      Estimates of population-level allele numbers fall within the range observed in
      the Solanaceae, the only other family with RNase-based incompatibility for which
      estimates are available. The nucleotide diversity of S-allele sequences was found
      to be much lower in the two Rosaceae species as compared with the Solanaceae.
      This was not due to a lower sequence divergence among most closely related
      alleles. Rather, it is the depth of the entire genealogy that differs markedly in
      the two families, with Rosaceae S-alleles exhibiting more recent apparent
      coalescence. We also investigated patterns of selection at the molecular level by
      comparing nucleotide diversity at synonymous and nonsynonymous sites. Stabilizing
      selection was inferred for the 5' region of the molecule, while evidence of
      diversifying selection was present elsewhere.

PMID- 12180089
TI  - Multiple origins of polyploidy in the phylogeny of southern African barbs
      (Cyprinidae) as inferred from mtDNA markers.
AB  - The cyprinid genus Barbus, with more than 800 nominal species, is an apparently
      polyphyletic assemblage to which a number of unrelated species, groups and/or
      assemblages have been assigned. It includes species that exhibit three different
      ploidy levels: diploid, tetraploid and hexaploid. Several lineages of the family
      Cyprinidae constitute a major component of the African freshwater ichthyofauna,
      having about 500 species, and fishes assigned to the genus 'Barbus' have the most
      species on the continent. We used complete sequences of the mitochondrial
      cytochrome b gene in order to infer phylogenetic relationships between diploid,
      tetraploid and hexaploid species of 'Barbus' occurring in southern Africa, the
      only region where representatives of all of the three ploidy levels occur. The
      results indicate that most of the lineages are incorrectly classified in the
      genus 'Barbus'. The southern African tetraploids probably originated from
      southern African diploids. They constitute a monophyletic group distinct from
      tetraploids occurring in the Euro-Mediterranean region (Barbus sensu stricto).
      The 'small' African diploid species seem to be paraphyletic, while the 'large'
      African hexaploid barbs species are of a single, recent origin and form a
      monophyletic group. The evidence of multiple, independent origins of polyploidy
      occurring in the African cyprinine cyprinids thus provides a significant
      contribution to the knowledge on the systematic diversity of these fishes, and
      warrants a thorough taxonomic reorganization of the genus.

PMID- 12180090
TI  - The effect of reproductive compensation on recessive disorders within
      consanguineous human populations.
AB  - We investigate the effects of consanguinity and population substructure on
      genetic health using the UK Asian population as an example. We review and expand
      upon previous treatments dealing with the deleterious effects of consanguinity on
      recessive disorders and consider how other factors, such as population
      substructure, may be of equal importance. For illustration, we quantify the
      relative risks of recessive lethal disorders by presenting some simple
      calculations that demonstrate the effect 'reproductive compensation' has on the
      maintenance of recessive alleles. The results show how reproductive compensation
      can effectively counteract the purging of deleterious alleles within
      consanguineous populations. Whereas inbreeding does not elevate the equilibrium
      frequency of affected individuals, reproductive compensation does. We suggest
      this effect must be built into interpretations of the incidence of genetic
      disease within populations such as the UK Asians. Information of this nature will
      benefit health care workers who inform such communities.

PMID- 12180091
TI  - Variation in heritability of tadpole growth: an experimental analysis.
AB  - Heritability characteristically shows large variation between traits, among
      populations and species, and through time. One of the reasons for this is its
      dependence on gene frequencies and how these are altered by selection and drift
      through the evolutionary process. We studied variation in heritability of tadpole
      growth rate in populations of the Swedish common frog, Rana temporaria. In
      populations evolving under warmer conditions, we have demonstrated elsewhere that
      tadpoles show better growth and physiological performance at relatively higher
      temperatures than tadpoles with an evolutionary history in a relatively cooler
      part of the distribution range. In the current study, we ask whether this process
      of divergence under natural selection has influenced the genetic architecture as
      visualised in estimates of heritability of growth rate at different temperature
      treatments under laboratory conditions. The results suggest that the additive
      genetic variance varies between treatments and is highest in a treatment that is
      common to both populations. Our estimates of narrow sense heritability are
      generally higher in the thermal regime that dominates in the natural environment.
      The reason for this appears not primarily to be because the component of additive
      genetic variation is higher in relation to the total phenotypic variation under
      these conditions, but because the part of the phenotypic variance explained by
      environmental variation increases at temperatures to which the current
      populations has been less frequently under selection.

PMID- 12180092
TI  - Environmental biotechnology regulatory affairs. Web alert.

PMID- 12180093
TI  - Challenges in applying microarrays to environmental studies.
AB  - Although DNA microarray technology has been used successfully to analyze global
      gene expression in pure cultures, it has not been rigorously tested and evaluated
      within the context of complex environmental samples. Adapting microarray
      hybridization for use in environmental studies faces several challenges
      associated with specificity, sensitivity and quantitation.

PMID- 12180094
TI  - Potential applications of DNA microarrays in biodefense-related diagnostics.
AB  - Recent years have witnessed a logarithmic growth in the number of applications
      involving DNA microarrays. Extrapolation of their use for infectious diagnostics
      and biodefense-related diagnostics seems obvious. Nevertheless, the application
      of DNA microarrays to biodefense-related diagnostics will depend on solving a set
      of substantial, yet approachable, technical and logistical problems that
      encompass diverse topics from amplification efficiency to bioinformatics.

PMID- 12180095
TI  - Molecular community analysis of microbial diversity.
AB  - New technologies that avoid the need for either gene amplification (e.g.
      microarrays) or nucleic acid extraction (e.g. in situ PCR) have recently been
      implemented in microbial ecology. Together with new approaches for culturing
      microorganisms and an increased understanding of the biases of molecular methods,
      these techniques form the most exciting advances in this field during the past
      year.

PMID- 12180096
TI  - Bacterial community composition and function in sewage treatment systems.
AB  - The application of modern molecular techniques has led to the identification, in
      situ quantification, and partial ecophysiological characterisation of bacteria
      responsible for bulking and foaming or for nutrient removal in sewage treatment
      systems. Unexpectedly, previously unrecognised, yet uncultured bacteria were
      demonstrated to catalyse nitrogen and phosphorous removal in activated-sludge and
      biofilm reactors. These findings provide the basis for the development of novel
      concepts for improving the efficiency and functional stability of waste water
      treatment systems.

PMID- 12180097
TI  - Developmental regulation of microbial biofilms.
AB  - Sophisticated molecular and microscopic methods used to study biofilm formation
      are rapidly broadening our understanding of surface-attached microbial
      communities in a wide variety of organisms. Regulatory mechanisms involved in the
      attachment and subsequent development of mature biofilms are being elucidated.
      Common themes are beginning to emerge, providing promise for the development of
      sophisticated control strategies.

PMID- 12180098
TI  - Disruption of bacterial quorum sensing by other organisms.
AB  - Higher plants and algae produce compounds that mimic quorum sensing: signals used
      by bacteria to regulate the expression of many genes and behaviors. Similarly,
      various bacteria can stimulate, inhibit or inactivate quorum sensing in other
      bacteria. These discoveries offer new opportunities to manipulate bacterial
      quorum sensing in applications relevant to medicine, agriculture and the
      environment.

PMID- 12180099
TI  - Phyllosphere microbiology.
AB  - Aerial plant surfaces harbor large numbers of microbes, some of which are
      deleterious to plants whereas others are benign or beneficial. Commercial
      formulations of bacteria antagonistic to plant pathogenic microbes and ice
      nucleation active bacteria have been utilized as an environmentally safe method
      to manage plant disease and to prevent frost damage. Molecular genetic tools,
      microscopic examination and whole-cell bacterial biosensors have provided
      extensive information on these microbes, their complex associations and their
      habitat. The aerial habitat influenced by plants, termed the phyllosphere, is
      particularly amenable to studies of microbial ecology and the information gained
      should lead to more effective means of plant protection.

PMID- 12180100
TI  - Linking marine biology and biotechnology.
AB  - Studies of biological systems in which there is a direct link between the
      challenges faced by marine organisms and biotechnologies enable us to rationally
      search for active natural compounds and other novel biotechnologies. This
      approach is proving successful in developing new methods for the prevention of
      marine biofouling and for the identification of new lead compounds for the
      development of ultraviolet sunscreens.

PMID- 12180101
TI  - Biosurfactants and oil bioremediation.
AB  - Oil pollution is an environmental problem of increasing importance. Hydrocarbon
      degrading microorganisms, adapted to grow and thrive in oil-containing
      environments, have an important role in the biological treatment of this
      pollution. One of the limiting factors in this process is the bioavailability of
      many fractions of the oil. The hydrocarbon-degrading microorganisms produce
      biosurfactants of diverse chemical nature and molecular size. These surface
      active materials increase the surface area of hydrophobic water-insoluble
      substrates and increase their bioavailability, thereby enhancing the growth of
      bacteria and the rate of bioremediation.

PMID- 12180102
TI  - Low-temperature extremophiles and their applications.
AB  - Psychrophilic (cold-adapted) organisms and their products have potential
      applications in a broad range of industrial, agricultural and medical processes.
      In order for growth to occur in low-temperature environments, all cellular
      components must adapt to the cold. This fact, in combination with the diversity
      of Archaea, Bacteria and Eucarya isolated from cold environments, highlights the
      breadth and type of biological products and processes that might be exploited for
      biotechnology. Relative to this undisputed potential, psychrophiles and their
      products are under-utilised in biotechnology; however, recent advances,
      particularly with cold-active enzymes, herald rapid growth for this burgeoning
      field.

PMID- 12180103
TI  - Fish spoilage bacteria--problems and solutions.
AB  - Microorganisms are the major cause of spoilage of most seafood products. However,
      only a few members of the microbial community, the specific spoilage organisms
      (SSOs), give rise to the offensive off-flavours associated with seafood spoilage.
      Combining microbial ecology, molecular techniques, analytical chemistry, sensory
      analysis and mathematical modelling allows us to characterise the SSOs and to
      develop methods to determine, predict and extend the shelf life of products.

PMID- 12180104
TI  - Ecology and physiology of infectious bacteria--implications for biotechnology.
AB  - Escalating incidents of life-threatening infections by antibiotic-resistant
      bacteria in recent years have provided strong impetus to discover new antibiotics
      and alternative treatment modalities. The need to couple information about
      bacterial physiology and ecology with innovative technologies will become ever
      more critical in the search for new antibiotics and for other therapies,
      including probiotics, improved vaccines, alternative antimicrobials and
      antitoxins.

PMID- 12180105
TI  - Understanding the puzzle of 'well-characterized biotechnology products'.
AB  - The concept of a 'well-characterized biotechnology product' is akin to assembling
      a jigsaw puzzle. Each of the analytical pieces must be assembled to provide a
      clearly, orthogonally defined picture that addresses completely the
      physicochemical, biological and pharmacological attributes that fully
      characterize the molecule.

PMID- 12180106
TI  - Prevention and management of CMV-related problems after hematopoietic stem cell
      transplantation.
AB  - Prevention and management of human cytomegalovirus (CMV) infection after
      hematopoietic stem cell transplantation has improved substantially in the past
      decade. However, with this improvement, there is increased complexity in deciding
      which diagnostic tests, treatment strategies and immunologic assessments are
      optimal for different patient populations. The purpose of this review is to
      address certain practical problems that commonly arise and suggest a suitable
      approach to management that should have wide applicability.

PMID- 12180108
TI  - A dose escalation study for salvage chemotherapy in patients with refractory
      lymphoma prior to high-dose myeloablative therapy with stem cell transplantation.
AB  - Chemosensitive response prior to transplantation has been shown to be most
      significant for survival post transplant. To estimate toxicity of a dose
      intensive regimen that was to improve chemosensitive response rate, 15 patients
      with primary refractory lymphoma were enrolled in dose escalation of pre
      transplant salvage chemotherapy. The first cycle had a fixed dose of ifosfamide 6
      g/m2 and mitoxantrone 12 mg/m2, with arabinosyl cytosine (Ara-C) 2 g/m2, and
      methylprednisolone 2.0 g. Each cycle of the second and third had cisplatin 90
      mg/m2, Ara-C 6 g/m2, methylprednisolone 2.0 g, and escalated doses of ifosfamide
      from 7.5 g/m2 to 15 g/m2 and mitoxantrone from 16 to 28 mg/m2. Blood stem cells
      were collected before the second cycle and > or = 3 x 10(6) CD34 cells/kg were
      infused 2 days after the second and third cycles, respectively. The maximum
      tolerated doses of ifosfamide and mitoxantrone were 11.25 g/m2 and 16 mg/m2,
      respectively. Acute renal failure and bacterial infection occurred as non
      hematologic dose limiting toxicities. Eleven patients completed therapy. Five
      patients achieved complete remission and five had partial remission. Nine
      patients received autologous and four received allogeneic transplants. Currently,
      six are alive without evidence of disease, with a 3-year survival of 40%.
      Although preliminary, the regimen suggests acceptable toxicity and significant
      activity that warrants further study.

PMID- 12180107
TI  - Allogeneic and autologous transplantation for haematological diseases, solid
      tumours and immune disorders: definitions and current practice in Europe.
AB  - The Accreditation Sub-Committee of the EBMT regularly publishes special reports
      on current practice of haemopoietic stem cell transplantation for haematological
      diseases, solid tumours and immune disorders. Major changes have occurred since
      the last report in 1998. Haemopoietic stem cell transplantation today includes
      allogeneic and autologous stem cells derived from bone marrow, peripheral blood
      and cord blood. With reduced intensity conditioning regimens in allogeneic
      transplantation, the age limit has increased, permitting the inclusion of older
      patients. New indications have emerged, such as autoimmune disorders and AL
      amyloidosis for autologous, and solid tumours for allogeneic transplants. Other
      indications, such as autologous transplantation for breast cancer have been
      challenged. An updated report with revised tables and operating definitions is
      presented here.

PMID- 12180109
TI  - Less frequent catheter dressing changes decrease local cutaneous toxicity of high
      dose chemotherapy in children, without increasing the rate of catheter-related
      infections: results of a randomised trial.
AB  - Cutaneous lesions caused by catheter dressing changes can be serious and generate
      local pain in children undergoing high-dose chemotherapy followed by bone marrow
      transplantation. One hundred and thirteen children entered a randomised trial to
      compare two catheter dressing change frequencies (15 days vs 4 days). Skin
      toxicity was classified according to the following scale: grade 0: healthy skin,
      to grade 4: severe skin toxicity. A qualitative culture of the skin at the
      catheter entry site was taken whenever the dressing was changed. Of the 112
      evaluable children (56 in each group) 32 developed grade > or = 2 local skin
      toxicity (eight in the 15-day group and 24 in the 4-day group; P = 0.001).
      Although higher in the 4-day group, the proportions of children experiencing pain
      during and between dressing changes were not statistically different between the
      two groups. The proportion of patients with one or more positive skin culture(s)
      at the catheter entry site during hospitalisation were similar in the two groups
      (27% in the 15-day group and 23% in the 4-day group) as were the proportions of
      documented nosocomial bloodstream infections (11% and 13%; NS). Whereas the
      planned frequency was maintained in the 4-day group (mean = 4 days, s.d. = 1), it
      was usually shortened in the 15-day group (mean = 8 days, s.d. = 4), mainly
      because dressings had loosened. Decreasing the catheter dressing change frequency
      proved efficient in reducing cutaneous toxicity without increasing the risk of
      local and systemic infection. In our unit, catheter dressings are changed every 8
      days since this analysis.

PMID- 12180110
TI  - Impact of high-dose chemotherapy on antigen-specific T cell immunity in breast
      cancer patients. Application of new flow cytometric method.
AB  - The present study analyses the influence of high-dose chemotherapy (HD) and
      autologous stem cell transplantation on natural and vaccine-induced specific
      immunity in breast cancer patients. Peripheral blood was collected from five
      breast cancer patients at serial time points in connection with treatment and in
      a follow-up period of 1 year. The frequencies of CD8+ and CD4+ T cells responsive
      to cytomegalovirus (CMV), varicella zoster virus (VZV), and tetanus in antigen
      activated whole blood were determined by flow cytometric analysis of CD69, TNF
      alpha, IFN gamma and IL-4 expression. Mononuclear cells were labelled with PKH26
      dye and the CMV, VZV, and tetanus toxoid-specific proliferation of T cell
      subpopulations was analysed by flow cytometry. In none of the patients did the
      treatment result in loss of overall T cell reactivity for any of the antigens.
      Prior to chemotherapy 5/5 patients possessed TNF alpha expressing T cells
      specific for CMV, 4/5 for VZV, and 3/5 for tetanus. One year after stem cell
      transplantation all patients possessed TNF alpha expressing T cells specific for
      CMV, VZV and tetanus. The highest percentages of cytokine-responding T cells were
      seen after stimulation with CMV antigen. In general, the lowest reactivity (close
      to zero) was measured in G-CSF-mobilised blood at the time of leukapheresis. In
      spite of a continuously reduced CD4 to CD8 ratio after transplantation, recovery
      of CD4+ T cells usually occurred prior to CD8+ recovery and often to a higher
      level. The study demonstrates that natural as well as vaccine-induced specific
      immunity established prior to HD can be regained after stem cell transplantation.
      These data indicate that introduction of a preventive cancer vaccination in
      combination with intensive chemotherapy may be a realistic treatment option.

PMID- 12180111
TI  - Outpatient total body irradiation as a component of a comprehensive outpatient
      transplant program.
AB  - Outpatient total body irradiation (TBI) as part of a comprehensive outpatient
      transplant program was delivered to 142 of 167 (85%) consecutive patients
      receiving TBI-based conditioning therapy. Outpatients received either a single
      fraction of 500 cGy (110 patients) or 1200 cGy in six fractions over 3 days (32
      patients). Patients were assessed daily and were administered oral ondansetron
      and dexamethasone for prophylaxis of nausea and vomiting as well as i.v.
      hydration. Accommodation during outpatient TBI-based conditioning was either the
      patient's home if within 30 min of the hospital, a hotel on the hospital grounds
      or on a closed hospital ward. None of the 142 patients required admission to the
      inpatient program during their TBI. There was no difference in 100-day mortality
      between those receiving TBI as an outpatient (9%) vs as an inpatient (16%). Of
      four deaths occurring within the first 14 days post transplant, none could be
      attributed to receiving TBI as an outpatient. Two hundred and six inpatient days
      were saved through the delivery of outpatient TBI. A comprehensive outpatient
      program, appropriate patient selection, daily hydration, the use of prophylactic
      5HT3 antagonist anti-emetic therapy all contribute to the safe delivery of
      outpatient TBI.

PMID- 12180112
TI  - Autologous hematopoietic cell transplantation non-Hodgkin's lymphoma: 100 month
      follow-up.
AB  - One hundred and ten adult patients with non-Hodgkin's lymphoma (NHL) received an
      autologous hematopoietic cell transplant (ABMT) from 1988 to 1993. All received a
      uniform preparative regimen of cyclophosphamide, BCNU and etoposide (CBV). Twenty
      one percent had low grade histologies, 54% intermediate grade, and 25% high
      grade. Median follow-up of 48 survivors is 100 months. Kaplan-Meier 10 year
      overall survival and relapse-free survival for the entire group is 42% and 32%,
      respectively. Fifty patients were in complete remission 2 years post transplant.
      With additional follow-up, patients with high grade malignancies are cured, while
      patients with intermediate or low grade histologies were at continued risk of
      relapse up to 5 years post transplant. Of 39 patients in complete remission 5
      years post transplant, none have relapsed with additional extended follow-up. We
      conclude that patients with NHL treated with ABMT, if in CR 5 years post
      transplant, are at very low risk of relapse with extended follow-up, suggesting
      the possibility of cure for all histologies, including those with low grade NHL.

PMID- 12180113
TI  - Transfusion-dependent congenital dyserythropoietic anemia type I successfully
      treated with allogeneic stem cell transplantation.
AB  - Until recently, therapy for patients with severe congenital dyserythropoietic
      anemia (CDA) has been limited to blood transfusions and chelation therapy. Three
      children with transfusion-dependent CDA type I underwent allogeneic stem cell
      transplantation (SCT) from matched sibling donors. Conditioning was with
      cyclophosphamide 50 mg/kg/day for 4 days, busulphan 4 mg/kg/day for 4 days, and
      antithymocyte globulin (ATG) 30 mg/kg for four doses pre-SCT. All patients
      engrafted and are alive, and transfusion independent. To our knowledge, this is
      the first report of successful SCT in the management of CDA type I.

PMID- 12180114
TI  - In vivo T cell depletion with pretransplant anti-thymocyte globulin reduces graft
      versus-host disease without increasing relapse in good risk myeloid leukemia
      patients after stem cell transplantation from matched related donors.
AB  - One-hundred and two patients with good risk myeloid leukemia (CML first chronic
      phase or AML first CR) were transplanted from HLA-related donors after
      conditioning with (n = 45) or without anti-thymocyte globulin (ATG) (n = 57). One
      graft failure was observed in the non-ATG and none in the ATG group. The median
      time to leukocyte engraftment (> 1 x 10(9)/l) was 16 (range 12-33) in the ATG
      group and 17 days (range 11-29) in the non-ATG group (NS) and for platelet
      engraftment (> 20 x 10(9)/l) 24 and 19 days (P = 0.002), respectively. Acute GVHD
      grade II-IV was observed in 47% of the non-ATG and in 20% of the ATG group (P =
      0.004). Grade III/IV GVHD occurred in 7% of the ATG and in 32% of the non-ATG
      group (P = 0.002). Chronic GVHD was seen in 36% and 67% (P = 0.005),
      respectively. After a median follow-up of 48 months (range 2-128), the 5-year
      estimated OS is 66% (95% KI: 51-81%) for the ATG group and 59% (95% KI: 46-72%)
      for the non-ATG group (NS). The 5-year estimated DFS is 64% (95% KI: 50-78%) for
      ATG and 55% (95% KI: 43-67%) for the non-ATG regimen (NS). The 5-year probability
      of relapse was 5% in the ATG and 15% in the non-ATG group (NS). ATG as part of
      the conditioning regimen leads to a significant reduction in GVHD without
      increase of relapse in patients with myeloid leukemia after stem cell
      transplantation from HLA-related donors.

PMID- 12180115
TI  - Toxoplasmosis in bone marrow transplantation: a report of two cases and
      systematic review of the literature.
AB  - Toxoplasma infection represents a rare but often fatal complication in bone
      marrow transplant (BMT) recipients. We report two cases of toxoplasmosis: one of
      successfully treated cerebral toxoplasmosis after peripheral blood stem cell
      transplantation, and a fatal case of pulmonary toxoplasmosis in a BMT recipient.
      We have systematically reviewed the 110 published cases of toxoplasmosis
      following BMT. We analyzed the pre-transplant and clinical features of BMT
      recipients developing toxoplasmosis, together with the diagnostic procedures used
      and treatment given. By univariate and multivariate statistical analysis we
      analyzed the risk factors for diagnosis (during life vs post-mortem) and
      Toxoplasma-related mortality. Ante-mortem diagnosis was made in 47% of cases.
      Site of infection (P = 0.02; odds ratio 10.8), presence of symptoms at onset (P =
      0.01) and conditioning regimen (P = 0.04) were factors influencing whether the
      diagnosis was made before or after death. Overall mortality rate was 80% and that
      attributed to toxoplasmosis was 66%. Variables influencing outcome were: site of
      infection (P = 0.02; odds ratio 5.28), day of onset (P = 0.04) and conditioning
      regimen (P = 0.04). Underlying disease (P = 0.02; odds ratio 9.45), among
      patients diagnosed before death, was the most significant factor influencing
      outcome.

PMID- 12180116
TI  - Assessing agreement between CD34 enumeration by flow cytometry and volumetric
      analysis.
AB  - Prior to replacement of an established method for CD34 enumeration by an
      alternative approach, evaluation of the agreement between the methods is
      essential. In this study, the comparison of two assays was evaluated according to
      the recommendation of Bland and Altman describing the agreement between two
      methods where the true value is not known. CD34 enumeration was performed on
      blood or leukapheresis product from 105 patients by flow cytometry (dual platform
      assay) and volumetric analysis (single platform assay). Both the flow cytometric
      and the volumetric analysis showed poor reproducibility for measures lower than
      approximately 9 CD34+ cells/mm3. For values higher than 29 CD34+ cells/mm3,
      evaluation of the agreement demonstrated a difference between the single and dual
      platform assay, where CD34 enumeration by the volumetric analysis demonstrated
      values 73-80% of the flow cytometric value. The difference between the two assays
      could be due to several technical pitfalls which are discussed.

PMID- 12180117
TI  - Reciprocal bone marrow transplantation between brother and sister.
AB  - A child with AML underwent allogeneic BMT from an HLA-identical sister donor.
      Prompt and stable triline-age engraftment occurred and after few months he
      returned to a normal life. Eight years later a primary NHL of bone developed in
      his sister. A partial remission was obtained by means of standard NHL treatment,
      but 3 months later rapid disease progression occurred with complete bone marrow
      invasion (ALL-L3). She was treated with a leukemia relapse protocol, obtaining a
      second partial remission. Unpurged bone marrow harvested from the brother,
      transplanted for AML 8 years earlier, was infused after conditioning with TBI and
      thiothepa. No GVHD prophylaxis was given. Neutrophil engraftment occurred by 14
      days and platelet engraftment by 20 days after BMT. No acute GVHD was observed,
      but unexpectedly she developed skin and liver GVHD-like symptoms 80 days after
      BMT. Since the liver biopsy was suggestive of liver GVHD and in the absence of
      any other evidence as a possible cause of the hepatic damage, the patient started
      mycophenolate. Two months later serum hepatitis B markers were detectable.

PMID- 12180118
TI  - Pseudoautologous blood stem cell transplantation for refractory chronic graft
      versus-host disease.
AB  - A female patient with AML received an allogeneic BMT from her brother. She
      experienced two relapses managed with chemotherapy and donor leukocyte infusions.
      The patient subsequently developed extensive therapy-refractory chronic GVHD.
      Pseudoautologous blood stem cell transplantation was performed as a salvage
      treatment for chronic GVHD. Her blood stem cells were easily mobilized with
      cyclophosphamide and G-CSF. The conditioning regimen was well tolerated and
      consisted of 200 mg/kg cyclophosphamide and horse-derived antithymocyte globulin.
      A total of 4.03 x 10(6)/kg CD34+ cells were infused and hematological recovery
      was rapid. Chronic GVHD improved with the ability to taper steroids. Nine months
      post transplantation the patient died from leukemia.

PMID- 12180119
TI  - Invasive airway aspergillosis with new airflow obstruction mimicking post-BMT
      bronchiolitis obliterans.
AB  - A 52-year-old male with severe gastrointestinal graft-versus-host disease (GVHD),
      developed dyspnea and irreversible airflow obstruction, 11 weeks post-allogeneic
      bone marrow stem cell transplantation. Based on the clinical picture and presence
      of 'mosaic attenuation' pattern on chest high-resolution computerized tomography
      (HRCT), he was presumed to have bone marrow transplantation-related bronchiolitis
      obliterans. Post-mortem examination revealed invasive airway aspergillosis with
      no evidence of bronchiolitis obliterans.

PMID- 12180120
TI  - Unusual cytomegalovirus complications after autologous stem cell transplantation
      for large B cell lymphoma: massive gastrointestinal hemorrhage followed by a
      communicating hydrocephalus.
AB  - Unusual cytomegalovirus (CMV)-related complications were seen after autologous
      stem cell transplantation (SCT) in a 50-year-old patient with diffuse large B
      cell lymphoma. One month after SCT, the patient developed life-threatening upper
      gastrointestinal tract (GIT) bleeding with several episodes of hemorrhagic shock.
      Endoscopy and subsequent explorative laparotomy revealed deep-seated bleeding
      ulcers containing intracellular CMV inclusion bodies distributed extensively in
      the GIT, from the lower esophagus to the small bowel. Later, she developed
      gradual loss of consciousness with communicating hydrocephalus which was possibly
      secondary to CMV-induced ventriculitis. She recovered completely after insertion
      of a ventriculostomy and subsequent V-P shunt.

PMID- 12180121
TI  - Increases in tumor necrosis factor-alpha in response to thyroid hormone-induced
      liver oxidative stress in the rat.
AB  - Thyroid hormone-induced calorigenesis contributes to liver oxidative stress and
      promotes an increased respiratory burst activity in Kupffer cells, which could
      conceivably increase the expression of redox-sensitive genes, including those
      coding for cytokines. Our aim was to test the hypothesis that L-3,3',5
      triiodothyronine (T3)-induced liver oxidative stress would markedly increase the
      production of TNF-alpha by Kupffer cells and its release into the circulation.
      Sprague-Dawley rats receive a single dose of 0.1 mg T3/kg or vehicle (controls)
      and determinations of liver O2 consumption, serum TNF-alpha, rectal temperature,
      and serum T3 levels, were carried out at different times after treatment. Hepatic
      content of total reduced glutathione (GSH) and biliary glutathione disulfide
      (GSSG) efflux were measured as indices of oxidative stress. In some studies,
      prior to T3 injection animals were administered either (i) the Kupffer cell
      inactivator gadolinium chloride (GdCl3), (ii) the antioxidants alpha-tocopherol
      and N-acetyl-L-cysteine (NAC), or (iii) an antisense oligonucleotide against TNF
      alpha (ASO TJU-2755). T3 elicited an 80-fold increase in the serum levels of TNF
      alpha at 22h after treatment, which coincided with the onset of thyroid
      calorigenesis. Pretreatment with GdCl3, alpha-tocopherol, NAC, and ASO TJU-2755
      virtually abolished this effect and markedly reduced T3-induced liver GSH
      depletion and the increases in biliary GSSG efflux. It is concluded that the
      hyperthyroid state in the rat increases the circulating levels of TNF-alpha by
      actions exerted at the Kupffer cell level and these are related to the oxidative
      stress status established in the liver by thyroid calorigenesis.

PMID- 12180122
TI  - Effects of antioxidants on surfactant peroxidation by stimulated human
      polymorphonuclear leukocytes.
AB  - Production of oxygen radicals by stimulated phagocytes followed by surfactant
      lipid peroxidation (LPO) and loss of surfactant function have all been implicated
      in the pathogenesis of acute lung injury. We studied the interactions between
      natural lung surfactant (Curosurf) and neutrophils in vitro, and compared various
      antioxidants; (superoxide dismutase (SOD), vitamin E, vitamin C, ebselen and
      melatonin), or combinations of them in duplicate and triplicate regarding their
      ability to decrease superoxide production and the peroxidation level of
      surfactant caused by activated phagocytes. The superoxide production of
      neutrophils activated by Candida albicans was measured with the nitroblue
      tetrazolium (NBT) test. The subsequent LPO was estimated as the content of
      malondialdehyde (MDA) and 4-hydroxyalkenals (4-HNE). We found that lung
      surfactant decreased the superoxide production by activated neutrophils (29.7%)
      and that Curosurf was peroxidized with elevated MDA/4-HNE values. With
      supplements of antioxidants (except vitamin C), superoxide radical production and
      the surfactant LPO level fell in a dose-dependent manner. The protective effect
      of the antioxidants differed in each test. SOD had a slight effect in both tests.
      The findings with vitamin E, melatonin and ebselen were similar. The best
      combination was that of a natural and a synthetic antioxidant (melatonin-ebselen)
      with a 60% decrease in comparison to the corresponding control. These findings
      suggest that antioxidants, particularly in combination, prevent LPO of lung
      surfactant.

PMID- 12180123
TI  - Decreased plasma and cerebrospinal fluid ascorbate levels in patients with septic
      encephalopathy.
AB  - Septic encephalopathies rapidly affect brain function without the involvement of
      a specific area causing a broad range of reversible neurologic symptoms.
      Capillary leakage including dysfunction of the blood-brain barrier has been
      proposed as a potential pathogenic mechanism in this entity. We tested the
      hypothesis that oxidative stress measured in plasma and cerebrospinal fluid (CSF)
      of patients suffering from septic encephalopathy could be linked to the
      neurologic symptoms of the disease. The neurologic symptoms of eleven patients
      with septic encephalopathy were described semiquantitatively through a score
      system. The ascorbate levels were significantly lower in both plasma and CSF from
      patients with septic encephalopathy than controls, and in CSF but not plasma this
      decrease correlated with the severity of neurologic symptoms. No significant
      changes were found for alpha-tocopherol. Our findings suggest that the short-term
      oxidative stress may be an important factor in the development of septic
      encephalopathy, possibly through dysregulation of the blood-brain barrier.

PMID- 12180125
TI  - Interaction of tert-butyl hydroperoxide with hypochlorous acid. A spin trapping
      and chemiluminescence study.
AB  - The formation of radical species during the reaction of ter-tbutyl hydroperoxide
      and hypochlorous acid has been investigated by spin trapping and
      chemiluminescence. A superposition of two signals appeared incubating tert-butyl
      hydroperoxide with hypochlorous acid in the presence of the spin trap alpha-(4
      pyridyl-1-oxide)-N-tert-butylnitrone (POBN). The first signal (aN = 1.537 mT, aH
      beta = 0.148 mT) was an oxidation product of POBN caused by the action of
      hypochlorous acid. The second spin adduct (aN = 1.484 mT, aH beta = 0.233 mT) was
      derived from a radical species that was formed in the result of reaction of tert
      butyl hydroperoxide with hypochlorous acid. Similarly, a superposition of two
      signals was also obtained using the spin trap N-tert-butyl-alpha-phenylnitrone
      (PBN). tert-Butyl hydroperoxide was also treated with Fe2+ or Ce4+ in the
      presence of POBN. Using Fe2+ a spin adduct with a N = 1.633 mT and aH beta =
      0.276 mT was observed. The major spin adduct formed with Ce4+ was characterised
      by a N = 1.480 mT and aH beta = 0.233 mT. The reaction of tert-butyl
      hydroperoxide with hypochlorous acid was accompanied by a light emission, that
      time profile and intensity were identical to those emission using Ce4+. The
      addition of Fe2+ to tert-butyl hydroperoxide yielded a much smaller
      chemiluminescence. Thus, tert-butyl hydroperoxide yielded in its reaction with
      hypochlorous acid or Ce4+ the same spin adduct and the same luminescence profile.
      Because Ce4+ is known to oxidize organic hydroperoxides to peroxyl radical
      species, it can be concluded that a similar reaction takes place in the case of
      hypochlorous acid.

PMID- 12180124
TI  - beta 2-glycoprotein I (apolipoprotein H) modulates uptake and endocytosis
      associated chemiluminescence in rat Kupffer cells.
AB  - beta 2-Glycoprotein I (beta 2 GPI) is known to influence macrophage uptake of
      particles with phosphatidylserine containing surfaces, as apoptotic thymocytes
      and unilamellar vesicles in vitro. Nevertheless, effects upon macrophage
      activation induced by this interaction are still unknown. beta 2 GPI influence
      upon the reactive species production by Kupffer cells was evaluated in order to
      investigate whether beta 2 GPI modulates the macrophage response to negatively
      charged surfaces. Chemiluminescence of isolated non-parenchymal rat liver cells
      was measured after phagocytosis of opsonized zymosan or phorbolymristate acetate
      (PMA) stimulation, in the presence and absence of large unilamellar vesicles
      (LUVs) containing 25 mol% phosphatidylserine (PS) or 50 mol% cardiolipin (CL) and
      complementary molar ratio of phosphatidylcholine (PC). beta 2 GPI decreased by
      50% the chemiluminescence response induced by opsonized zymosan, with a 66%
      reduction of the initial light emission rate. PMA stimulated Kupffer cell
      chemiluminescence was insensitive to human or rat beta 2 GPI. Albumin (500
      micrograms/ml) showed no effect upon chemiluminescence. beta 2 GPI increased
      PS/PC LUV uptake and degradation by Kupffer cells in a concentration-dependent
      manner, without leakage of the internal contents of the LUVs, as shown by
      fluorescence intensity enhancement. LUVs opsonized with antiphospholipid
      antibodies (aPL) from syphilitic patients increased light emission by Kupffer
      cells. Addition of beta 2 GPI to the assay reduced chemiluminescence due to
      opsonization with purified IgG antibodies from systemic lupus erythematosus (SLE
      or syphilis (Sy) patient sera. A marked net increase in chemiluminescence is
      observed in the presence of Sy aPL antibodies, whereas a decrease was found when
      SLE aPL were added to the assay, in the presence or absence of beta 2 GPI. At a
      concentration of 125 micrograms/ml, beta 2 GPI significantly reduced Kupffer cell
      Candida albicans phagocytosis index and killing score by 50 and 10%,
      respectively. The present data strongly suggest that particle uptake in the
      presence of beta 2 GPI is coupled to an inhibition of reactive species production
      by liver macrophages during the respiratory burst, supporting the role of beta 2
      GPI as a mediator of senescent cell removal.

PMID- 12180126
TI  - Nitric oxide and blood pressure in mice lacking extracellular-superoxide
      dismutase.
AB  - Nitric oxide is a major vasorelaxant and regulator of the blood pressure. The
      blood vessels contain several active sources of the superoxide radical, which
      reacts avidly with nitric oxide to form noxious peroxynitrite. There are large
      amounts of extracellular-superoxide dismutase (EC-SOD) in the vascular wall. To
      evaluate the importance of EC-SOD for the physiology of nitric oxide, here we
      studied the blood pressure in mice lacking the enzyme. In chronically
      instrumented non-anaesthetized mice there was no difference in mean arterial
      blood pressure between wild-type controls and EC-SOD mutants. Extensive
      inhibition of nitric oxide synthases with N-monomethyl-L-arginine however
      resulted in a larger increase in blood pressure, and infusion of the nitric oxide
      donor nitrosoglutathione caused less reduction in blood pressure in the EC-SOD
      null mice. We interpret the alterations to be caused by a moderately increased
      consumption of nitric oxide by the superoxide radical in the EC-SOD null mice.
      One role of EC-SOD may be to preserve nitric oxide, a function that should be
      particularly important in vascular pathologies, in which large increases in
      superoxide formation have been documented.

PMID- 12180127
TI  - Differences in mRNA expression, protein content, and enzyme activity of
      superoxide dismutases in type II pneumocytes of acute and chronic lung injury.
AB  - The lung is protected against oxidative stress by a variety of antioxidants and
      type II pneumocytes seem to play an important role in antioxidant defense.
      Previous studies have shown that inhalation of NO2 results in acute and chronic
      lung injury. How the expression and enzyme activity of antioxidant enzymes are
      influenced in type II cells of different inflammatory stages has yet not been
      studied. To elucidate this question, we exposed rats to 10 ppm NO2 for 3 or 20
      days to induce acute or chronic lung injury. From these and air-breathing rats,
      type II pneumocytes were isolated. The mRNA expression and protein content of
      CuZnSOD and MnSOD as well as total SOD-specific enzyme activity were determined.
      For the acute lung injury (3 d NO2), the expression of CuZnSOD mRNA was
      significantly increased, while MnSOD expression was significantly reduced after 3
      days of NO2 exposure. For the chronic lung injury (20 d NO2), CuZnSOD expression
      was still enhanced, while MnSOD expression was comparable to control. In parallel
      to CuZnSOD mRNA expression, the protein amount was significantly increased in
      acute and chronic lung injury however MnSOD protein content exhibited no
      intergroup differences. Total SOD enzyme activity showed a significant decrease
      after 3 days of NO2 exposure and was similar to control after 20 days. We
      conclude that during acute and chronic lung injury in type II pneumocytes
      expression and protein synthesis of CuZnSOD and MnSOD are regulated differently.

PMID- 12180128
TI  - Effects of oxicam inhibitors of cyclooxygenase on oxidative stress generation in
      rat gastric mucosa. A comparative study.
AB  - The aim of this study was to compare the effects of two nonsteroidal anti
      inflammatory drugs (NSAID), members of the same family with a different
      cyclooxygenase (COX) inhibition selectivity, meloxicam, preferent COX-2
      inhibitor, and piroxicam, preferent COX-1 inhibitor, on oxygen radical generation
      in rat gastric mucosa. Therefore, the activity of oxidative stress-related
      enzymes such as xanthine oxidase (XO), superoxide dismutase (SOD) and glutathione
      (GSH) homeostasis were studied in rats. Gastric prostaglandins (PG) were also
      assessed as a measure of COX-1 inhibition. Both oxicams produced a similar extent
      of the gastric mucosal damage and a significant decrease in PGE2 synthesis,
      however only piroxicam induced an increase of both myeloperoxidase (MPO) activity
      and tumor necrosis factor (TNF)-alpha content in the gastric mucosa, indicating
      that neutrophil-derived free radicals were involved in gastric injury.
      Furthermore, both compounds reduced SOD activity and increased XO activity in
      gastric mucosa. Our results also revealed modifications in GSH metabolism:
      although glutathione peroxidase (GSH-px) activity was unaffected by meloxicam or
      piroxicam administration, both glutathione reductase (GSSG-rd) activity and total
      GSH content were significantly decreased after dosing. These results suggest that
      under our experimental conditions, meloxicam, preferential COX-2 inhibitor causes
      rates of gastric lesion in rats comparable to those seen with the traditional
      NSAID piroxicam, preferential COX-1 inhibitor. In addition to suppression of
      systemic COX activity, oxygen radicals, probably derived via the XO, and
      neutrophils play an important role in the production of damage induced by both
      oxicams. Moreover, the decrease in SOD activity and changes in glutathione
      homeostasis in gastric mucosa may also contribute to pathogenesis of meloxicam-
      or piroxicam-induced gastropathy.

PMID- 12180129
TI  - Large differences in erythrocyte stability between species reflect different
      antioxidative defense mechanisms.
AB  - We have developed a screening assay for erythrocyte stability, which is rapid,
      easy, inexpensive, robust, and suitable for handling a large number of samples in
      parallel. Erythrocytes are incubated overnight in 96-well microtiter plates in
      absence or presence of various oxidants, intact cells are pelleted by
      centrifugation, and lysis is determined by release of intracellular constituents
      into the supernatant as either activity of lactate dehydrogenase (LDH) or
      absorbance of hemoglobin at 406 nm. There is good correlation between the
      methods. A number of advantages by the present method are that only small amounts
      of blood is needed, washing is optional, erythrocytes may be stored for at least
      one day before assay, and large numbers of samples can be handled in parallel.
      Using this set-up, we have compared erythrocyte stability from several different
      animal species. We find that erythrocyte susceptibility towards lysis induced by
      H2O2 and 2,2'-azobis (2-amidinopropane) dihydrochloride (AAPH) is highly species
      dependent. The different susceptibility between species is due to cellular
      components, since swapping of plasma between species has little or no effect. As
      a novel observation, we find that erythrocytes from chicken are the most
      sensitive of the species tested towards lysis by H2O2 and are almost four orders
      of magnitude more sensitive than erythrocytes from man. This is due to a much
      lower content of catalase in erythrocytes from chicken. A more narrow range is
      observed for susceptibility towards AAPH and the ranking between the species is
      different. Thus, chicken erythrocytes are more resistant towards AAPH than some
      mammals by up to two orders of magnitude. This differential stability towards
      different oxidative stressors is likely due to evolution/selection of different
      defense mechanisms.

PMID- 12180131
TI  - Effects of food processing on flavonoids and lycopene status in a Mediterranean
      tomato variety.
AB  - This research is focused on the antioxidant properties of dietary components, in
      particular phenolics and carotenoids and the assessment of the contribution of
      the combined antioxidants to the total antioxidant activity (TAA) of tomato
      fruit. The aim of this study was to analyse the effects of processing on the
      antioxidant properties of tomato. The effects of three different methods of
      processing fresh tomatoes into tomato sauce were investigated with respect to the
      antioxidant properties of the fruit. Identification and quantification of the
      main carotenoids and flavonoids present in tomatoes was achieved by HPLC analysis
      and the effect on the concentration and availability of these compounds was
      investigated at different stages of the processing. The processing affected
      mainly naringenin causing a reduction in the concentration. Conversely, levels of
      chlorogenic acid were increased suggesting an improvement in availability of this
      compound to extraction. The concentration of all-trans-lycopene was also
      increased following processing. Less than 10% isomerisation of all-trans-lycopene
      to the cis form was detected for all the methods analysed. The effects of
      processing on the overall antioxidant activity support the theory of a general
      improvement in availability of individual antioxidants. For both hydrophilic and
      lipophilic extracts TAA values were increased.

PMID- 12180130
TI  - Carotenoids induce apoptosis in the T-lymphoblast cell line Jurkat E6.1.
AB  - Epidemiologically, a high-carotenoid intake via a fruit- and vegetable-rich diet
      is associated with a decreased risk of various forms of cancer. The mechanisms by
      which carotenoids exert this protective effect are controversial. In this study,
      we examined the potency of a range of carotenoids commonly found in human plasma
      to induce apoptosis in Jurkat E6.1 malignant T-lymphoblast cells. At a
      concentration of 20 microM, the order of potency to induce apoptosis after 24 h
      was: beta-carotene > lycopene > lutein > beta-cryptoxanthin = zeaxanthin.
      Canthaxanthin failed to induce apoptosis under these conditions. beta-Carotene
      induced apoptosis in a time- and concentration-dependent manner with a lowest
      effective concentration of about 3 microM. Pre-conditioning of beta-carotene for
      72 h destroyed its pro-apoptotic activity almost completely, whereas degradation
      for 6 h or less did not, indicating that either beta-carotene itself and/or an
      early degradation product of beta-carotene are the death-inducing compounds.
      Apoptosis induced by beta-carotene was characterized by chromatin condensation
      and nuclear fragmentation, DNA degradation, PARP cleavage and caspase-3
      activation. The antioxidant BO-653 inhibited the degradation of beta-carotene in
      vitro and significantly increased its cytotoxicity, indicating that a pro-oxidant
      effect of beta-carotene is unlikely to cause its pro-apoptotic activity. The
      induction of apoptosis in transformed cells by carotenoids may explain their
      protective effect against cancer formation in humans. Possible pathways for
      induction of apoptosis by carotenoids are discussed.

PMID- 12180132
TI  - Molecular cloning, genomic organization, and mapping of beta 4GalT-VIb, a brain
      abundant member of beta 4-galactosyltransferase gene family, to human chromosome
      18q12.1.
AB  - In the present study, a brain abundant member of beta 4-galactosyltransferase
      gene family with an open reading frame encoding 343 amino acids was cloned and
      identified from a human leukemia cell cDNA library. The putative protein sequence
      is about 94.8 and 94.2% identical to the 382-amino-acid mouse and rat beta 4
      galactosyltransferase respectively and also contains cysteine residues previously
      shown to be important for the function of the gene family members. This cDNA
      (tentatively termed beta 4GalT-VIb) is identical to a recently reported cDNA
      (tentatively termed beta 4GalT-VIa) of human beta 4-galactosyltransferase except
      lacking one exon, suggesting that these two cDNAs are two different alternative
      transcripts of the same gene. Northern hybridization showed that the new
      alternative transcript, beta 4GalT-VIb, is expressed in all 16 human tissues
      tested with highest level in brain and rich level in testis, thymus and pancreas,
      whereas weak expression was detected in lung. The beta 4GalT-VIb gene was located
      to human chromosome 18q12.1 between markers WI-9180 and SGC35630 by radiation
      hybrid mapping. The genomic organization and adjacent gene content of beta 4GalT
      VIb were identified by comparing its cDNA sequence with three genomic sequences
      AC017100, AP002474 and AP001336, which showed that beta 4GalT-VIb spans an
      approximately 58 kb region and is composed of 8 exons. In addition, the most
      conserved motif composed of 41 residues, LXYX3FGGVSXL(T/S)X2
      QFX2INGFPNX(Y/F)WGWGGEDDDX2NR, was defined according to 17 sequences of beta
      4GalTs from seven different organisms for the first time.

PMID- 12180133
TI  - Cloning and tissue-specific expression of spliced variants of the rat organic
      anion transporter (rOAT-K).
AB  - During the last decade, molecular cloning has identified several families of
      multispecific organic ion transporters mediating the renal and hepatic
      elimination of organic ions. Clinically, these transporters play important roles
      in the renal tubular secretion and reabsorption of various drugs. They are also
      in part responsible for the drug pharmacologic responses, drug-drug interactions,
      and drug nephrotoxicity. This study describes 12 novel isoforms of the rat kidney
      organic anion transporter rOAT-K. These isoforms are spliced variants of the same
      gene arising from alternative splicing of six regions defined as A-F. The two
      previously reported isoforms rOAT-K1 and rOAT-K2 were also found to be spliced
      variants of this gene. The open reading frames of the 12 isoforms encode a range
      of 352-670 amino acid proteins. Tissue distribution studies showed that the
      majority of the isoforms are kidney- and liver-specific.

PMID- 12180134
TI  - A major substrate for MPF: cDNA cloning and expression of polypeptide chain
      elongation factor 1 gamma from goldfish (Carassius auratus).
AB  - One of the eukaryotic polypeptide chain elongation factors, EF-1 beta gamma delta
      complex, is involved in polypeptide chain elongation via the GDP/GTP exchange
      activity of EF-1 alpha. In the complex, EF-1 gamma has been reported to be a
      major substrate for maturation promoting factor (MPF). Here, we present the
      cloning, sequencing and expression analysis of goldfish, Carassius auratus, EF-1
      gamma from the goldfish ovary. The cloned cDNA was 1490 bp in length and encoded
      442 amino acids. The deduced amino acid sequence was highly homologous to EF-1
      gamma from other species. Although, the phosphorylation site identified in
      Xenopus EF-1 gamma was not conserved in the goldfish homologue, phosphorylation
      analysis showed that the goldfish EF-1 gamma was phosphorylated by MPF. We
      concluded that EF-1 gamma is a substrate for MPF during oocyte maturation in
      goldfish.

PMID- 12180135
TI  - Molecular analysis of an endopolygalacturonase gene from a Eucalyptus canker
      pathogen, Cryphonectria cubensis.
AB  - Cryphonectria cubensis causes a serious Eucalyptus canker disease. Fungal cell
      wall degrading enzymes (CWDEs) are important during the early stages of
      interaction of the fungus with Eucalyptus. To improve our understanding of the
      molecular regulation of the interaction of Eucalyptus and C. cubensis, the
      relevant genes involved in this interaction should be identified, cloned and
      studied. The aim of this study was, therefore, to clone the endopolygalacturonase
      (endoPG) gene of C. cubensis. C. cubensis was grown on a medium supplemented with
      Eucalyptus cell wall extracts. Degenerate primers were designed to amplify part
      of the endoPG gene from C. cubensis genomic DNA. The resulting sequence was used
      to design specific primers for use in inverse PCR to amplify the entire endoPG
      gene of C. cubensis (ccen-1). The endoPG sequence of C. cubensis has 93% amino
      acid sequence similarity to that of the chestnut blight pathogen, Cryphonectria
      parasitica.

PMID- 12180136
TI  - Isolation and sequencing of a putative promoter region of the murine G protein
      beta 1 subunit (GNB1) gene.
AB  - The expression of the heterotrimeric GTP-binding protein beta 1 subunit gene
      (GNB1) is regulated by psychostimulants such as cocaine and amphetamines. Since
      the up-regulation appears to be one of the candidate processes of sensitization,
      it is necessary to elucidate the cellular and molecular mechanism of the GNB1
      gene regulation for a better understanding the establishment of sensitization. In
      the present study, we describe the isolation and nucleotide sequence analysis of
      the GNB1 gene promoter region. We have isolated approximately 10 kb of the 5'
      flanking region of the mouse of GNB1 gene and found potential elements involved
      in putative transcriptional control of the GNB1, such as AP1, AP2, Sp1, cyclic
      AMP response element, and nuclear factor kappa B recognition sites, within the
      sequences 0.3 kb upstream from the putative transcription start site. This region
      was highly rich in G + C content, but lacked TATA or CATT boxes. Comparing the
      nucleotide sequence of the cDNA clone with the human genome databases using the
      BLAST program a region containing putative exon 1 and promoter of the human GNB1
      gene in chromosome 1 was found. The cloning and sequence analysis of an extensive
      portion of the 5'-flanking regulatory region of the GNB1 gene provides new
      insights into the factors involved in the regulation by psychostimulants of GNB1
      expression.

PMID- 12180137
TI  - cDNA cloning and molecular characterization of mink SMAD4.
AB  - The Smad family of proteins have been implicated as major components of the TGF
      beta signalling pathway and are important mediators of its pleiotrophic effects.
      Here we describe the cloning and characterization of the mink (Mustela vison)
      ortholog of Smad4. Mink Smad4 has a high level of conservation to its human
      counterpart showing 96% homology at the DNA level and 99% at the amino acid
      level. This is in agreement with the close homologies seen for the rat and mouse
      orthologs. In vitro transcription and translation shows the expression of a
      protein of predicted molecular weight, of identical size to its human
      counterpart.

PMID- 12180138
TI  - Genomic cloning of Xenopus TFIIS (TCEA1) and identification of its transcription
      start site.
AB  - We previously cloned the cDNA of the transcription factor TFIIS (SII) from
      Xenopus laevis and showed that its expression was not constant during Xenopus
      development. To investigate its regulation, we cloned the genomic DNA of Xenopus
      TFIIS, focusing on the 5'-promoter region. Here, we present the Xenopus TFIIS
      genomic sequence (-1730 to +214) and transcription start site (cap site). We
      define the position of the primary cap site as the adenine located 142 bp
      upstream from the adenine of the ATG (Met) codon. Another putative start-site
      region, where 13 transcriptional start sites are clustered within 12 bp, was
      mapped about 100 bp downstream of the primary cap site. Although a computer
      search found putative trans-element binding sites proximal to two Xenopus TFIIS
      transcription start sites, we could not identify typical "TATA" or "CAATT" boxes
      upstream of the primary cap site, probably owing to TFIIS's character as a "house
      keeping gene".

PMID- 12180139
TI  - Na-ctl-2, a cDNA encoding a C-type lectin expressed exclusively in adult Necator
      americanus hookworms.
AB  - C-type lectins (C-TLs) are carbohydrate-binding proteins central to diverse
      physiological processes including immunity, venom-induced haemostasis and wound
      repair. Here we describe the cloning of Na-ctl-2, a cDNA encoding a secreted C-TL
      from the human hookworm Necator americanus. The transcript was detected in mRNA
      from adult worms but not infective larvae. The cDNA encoded an N-terminal
      secretory signal peptide followed by a long-form C-TL domain with sequence
      similarity to C-TL-like proteins from Caenorhabditis elegans and mammalian
      antigen presenting cell receptors, suggesting that hookworms might utilise this
      class of lectin to interrupt anti-parasite immune responses or interfere with
      host clotting mechanisms. This is the first report of a full-length cDNA encoding
      a lectin from hookworms. The unusually skewed representation of this protein
      family within different nematode genera and its subsequent impact on the
      evolution of nematode parasitism is discussed.

PMID- 12180140
TI  - Isolation and sequence analysis of the GlnKamtB1amtB2 gene cluster, encoding a
      PII homologue and two putative ammonium transporters, from Pseudomonas stutzeri
      A15.
AB  - By PCR, using primers based on heterologous amtB genes, an amtB sequence of
      Pseudomonas stutzeri A15 was amplified. This DNA fragment was used as a probe in
      Southern hybridisation experiments and resulted in the isolation and sequence
      analysis of a 6017 bp genomic fragment of P. stutzeri A15 containing
      glnKamtB1amtB2. GlnK codes for a homologue of the nitrogen regulatory PII
      protein, amtB1 and amtB2 encode putative ammonium transporters. Whereas a
      glnKamtB gene cluster is common among bacteria, a tandem repeat of ammonium
      transporter genes has not been reported before. Apart from the presence of a
      second amtB gene, the gene organisation on this 6 kbp fragment is very similar to
      a particular region in the genome of Pseudomonas aeruginosa PAO1, relatively
      closely related to P. stutzeri. Furthermore, the amtB1 gene shows the highest
      similarity with P. aeruginosa amtB, whereas the amtB2 gene is more closely
      related to cyanobacterial amtB genes, which are reported to be monocistronically
      transcribed and not clustered with glnK homologues. Upstream of glnK, NtrC and
      RpoN recognition sites can be observed. In the intergenic region of
      glnKamtB1amtB2 no terminators nor extra promoter sequences were observed,
      indicating that glnKamtB1amtB2 is possibly transcribed as a nitrogen regulated
      operon.

PMID- 12180141
TI  - Determination of haploid DNA sequences in humans: application to the
      glucocerebrosidase pseudogene.
AB  - Variation analyses in the human genome at the sequence level, especially human
      genetic population analysis and genetic epidemiology, are hampered by the
      difficulty to ascertain haplotypes on autosomal regions. We have designed a new
      methodological approach to obtain autosomal haploid sequences from diploid
      organisms. First, genotypes are unambiguously determined through long-range PCR
      and diploid DNA sequencing. Second, cloning the whole PCR-amplified segment and
      sequencing a single clone for those fragments that presented a heterozygous
      position discern the allelic phase. The second allele is deduced from the
      genotype, and the phase reconfirmed by sequencing a second clone. A hundred human
      chromosomes were analysed for a 5.4 kb encompassing the glucocerebrosidase
      pseudogene on human chromosome 1. Haplotypes were unambiguously ascertained for
      all samples. The manner to combine the used techniques makes this approach a
      novelty. Haploid sequences from diploid organisms are obtained in a less time
      consuming and more accurate manner than in other used procedures.

PMID- 12180142
TI  - Will there be funds to support essential clinical genetic services?

PMID- 12180143
TI  - Cardiovascular disease in neurofibromatosis 1: report of the NF1 Cardiovascular
      Task Force.
AB  - PURPOSE: Patients with neurofibromatosis 1 (NF1) are at increased risk for a
      variety of cardiovascular disorders, but the natural history and pathogenesis of
      these abnormalities are poorly understood. METHODS: The National
      Neurofibromatosis Foundation convened an expert task force to review current
      knowledge about cardiovascular manifestations of NF1 and to make recommendations
      regarding clinical management and research priorities related to these features
      of the disease. RESULTS: This report summarizes the NF1 Cardiovascular Task
      Force's current understanding of vasculopathy, hypertension, and congenital heart
      defects that occur in association with NF1. Recommendations are made regarding
      routine surveillance for cardiovascular disease and diagnostic evaluation and
      management of cardiovascular disorders in individuals with NF1. CONCLUSION: Our
      understanding of the natural history and pathogenesis of cardiovascular disease
      in NF1 has improved substantially in the past few years, but many clinically
      important questions remain unanswered.

PMID- 12180144
TI  - Prevalence of aortic root dilation in the Ehlers-Danlos syndrome.
AB  - PURPOSE: To determine the prevalence of proximal aortic abnormalities in patients
      with Ehlers-Danlos syndrome (EDS). METHODS: In a prospective cohort study, aortic
      measurements by two-dimensional echocardiography were performed on consecutive
      EDS patients. RESULTS: Twenty-eight percent (20 of 71) had aortic root dilation
      (ARD) (> +2 SD above population based norms). Fourteen of 42 individuals with the
      classical form of EDS (types I/II) and 6 of 29 individuals with the hypermobile
      form (type III) had ARD, with no gender differences. CONCLUSION: ARD is a common
      finding in EDS. Longitudinal studies are indicated to determine progression of
      ARD and its clinical significance.

PMID- 12180145
TI  - Hypercholesterolemia in children with Smith-Magenis syndrome: del (17)
      (p11.2p11.2).
AB  - PURPOSE: Smith-Magenis syndrome (SMS), a probable contiguous gene syndrome due to
      an interstitial deletion of chromosome 17 band p11.2, is associated with a
      distinct and complex phenotype, including physical, developmental, and
      neurobehavioral features. The majority of SMS patients are deleted for a common
      approximately 4 Mb interval that includes the gene SREBF1, a transmembrane
      transcription factor that regulates the low density lipoprotein (LDL) receptor
      and plays a crucial role in cholesterol homeostasis. A systematic study of
      fasting lipid profiles of patients with SMS was conducted to determine the
      frequency of cholesterol abnormalities. METHODS: Fasting lipid profiles were
      examined in 49 children (27F/22M) between the ages of 0.6 years to 17.6 years
      (mean, 6.9 years) with a cytogenetically confirmed diagnosis of SMS. Observed
      values for serum total cholesterol (TC), triglycerides (TG), LDL cholesterol, and
      high density lipoprotein cholesterol were compared with published norms. The body
      mass index (BMI) was used as a measure of nutritional status. RESULTS: Mean TC
      was significantly higher than published NHANES III pediatric norms (P < 0.0008).
      Overall 28 of 49 (57%) SMS subjects had lipid values greater than the 95th
      percentile for age and gender for at least one or more of the following: TC, TG,
      and/or LDL. Only 16 SMS subjects (32%) were within normal limits for all three of
      these variables. BMI values showed minimal positive correlation to SMS lipid
      values; however, no consistent effect was found. Thus BMI values alone do not
      explain the marked trend in increased TC, TG, and/or LDL observed in the SMS
      group. Based on the American Academy of Pediatrics recommended lipid levels for
      children and adolescents, only one third of SMS subjects fall within normal range
      for TC and LDL; an additional one third each measure "borderline" or "high" for
      these values. CONCLUSION: Hypercholesterolemia is common in SMS and may serve as
      a useful early clinical biochemical marker of the syndrome.

PMID- 12180146
TI  - Spina bifida and folate-related genes: a study of gene-gene interactions.
AB  - PURPOSE: To assess whether interactions of common alleles of two folate genes
      contribute to spina bifida risk. METHODS: Case-control study, comparing 203
      children with spina bifida to 583 controls. RESULTS: Homozygosity for the 677C-T
      allele of 5,10-methylenetetrahydrofolate reductase (MTHFR) alone was associated
      with an odds ratio for spina bifida of 1.57 (95% confidence interval [CI], 1.02
      2.38). For the 844ins68 allele of cystathionine-beta-synthase alone, the odds
      ratio was 0.83 (95% CI, 0.39-1.64). For the joint genotype, the odds ratio was
      3.69 (95% CI, 1.04-13.50). CONCLUSIONS: Interactions between common alleles of
      folate genes might contribute to the risk for spina bifida.

PMID- 12180147
TI  - Prevalence of aneuploidies in South Carolina in the 1990s.
AB  - PURPOSE: Folate insufficiency due to nutritional deficiency or folate processing
      gene mutations has been proposed as a trisomy 21 risk factor. This study examined
      the possibility that increased folic acid intake among women of childbearing age
      may decrease the prevalence of trisomy 21 and other aneuploidies. METHODS: The
      prevalence of aneuploidies from 1990 through 1999 was compared with folic acid
      use in women of childbearing age in South Carolina. RESULTS: Folic acid use and
      the prevalence of all aneuploidies significantly increased during this period.
      CONCLUSION: Increased folic acid utilization in South Carolina was not associated
      with decreased prevalence of trisomy 21 or other aneuploidies.

PMID- 12180148
TI  - Survey of physician knowledge about hemochromatosis.
AB  - PURPOSE: To survey physicians about knowledge of hemochromatosis. METHODS: A
      questionnaire was faxed to American physicians. RESULTS: A total of 2,563
      evaluable responses were obtained. There were > or = 70% correct responses about
      at-risk population, associated abnormalities, and population screening. There
      were 32% and 53% correct answers about diagnosis and treatment, respectively. A
      total of 8.0% and 4.9% reported asking > 75% of patients about family history of
      hemochromatosis and iron overload, respectively. Less than 25% requested HFE
      mutation analysis in the previous year. Correct answers were associated with
      academic practice, internal medicine specialty, and medical school graduation
      within 10 years. CONCLUSION: Many physicians have inadequate knowledge about
      hemochromatosis diagnosis and treatment.

PMID- 12180149
TI  - The practice of clinical genetics: a survey of practitioners.
AB  - PURPOSE: A survey of clinical geneticists was undertaken to learn more about
      current practice. METHODS: An attempt was made to survey all geneticists
      practicing in the United States to elicit information on a variety of issues.
      RESULTS: A total of 69% of geneticists responded. Most practice at a medical
      school, most receive a portion of their income from salary, and many receive
      personal financial support from research grants. CONCLUSION: The specialty of
      medical genetics is primarily housed in tertiary care settings. Although a
      substantial amount of time is required to see patients, reimbursement for these
      services does not cover the costs to maintain such practices.

PMID- 12180151
TI  - Eight novel mutations in the HEXA gene.
AB  - PURPOSE: To characterize novel mutations in the HEXA gene (alpha-subunit beta
      hexosaminidase A). METHODS: Subjects included participants in the California Tay
      Sachs disease prevention program. DNA samples from 49 subjects (47 enzymatically
      defined carriers and 2 disease afflicted) who were negative for the four common
      disease-associated and the two pseudodeficient mutations, were subjected to
      single-strand conformation polymorphism (SSCP) analysis over 14 exons. RESULTS:
      Targeted sequencing of the 39 electrophoretic variants from SSCP analysis
      revealed eight novel and deleterious mutations and 31 with previously described
      mutations. Six novel mutations were found in non-Jewish carriers, and two were
      found in two patients with infantile Tay-Sachs disease. CONCLUSION:
      Identification of these eight novel mutations provides additional insight to the
      mutational spectrum for the HEXA gene. Furthermore, this knowledge should enhance
      diagnosis and prognosis for Tay-Sachs disease, carrier identification, and
      fundamental studies in structure/function relationships between this gene and its
      enzymatic product.

PMID- 12180150
TI  - Patient preferences of decision-making in the context of genetic testing for
      breast cancer risk.
AB  - PURPOSE: We conducted a study on women's preferred physician involvement in the
      decision to obtain genetic testing for breast cancer risk. METHODS: Women from a
      primary care physician network completed a telephone survey and a written
      baseline questionnaire. RESULTS: The majority preferred to make up their own
      minds. Predictors of leaving the decision to providers were less education, less
      knowledge, and higher external health locus of control. Trust in one's physician
      mediated the effect of health locus of control on decision method. CONCLUSION:
      Physicians will face requests from low-risk women and will need effective
      communication skills to inform women about the test.

PMID- 12180153
TI  - Designing the ambulatory endoscopy center.
AB  - Designing the ambulatory endoscopy center (AEC) covers the factors necessary to
      develop a design for a full-service endoscopy service based on patient comfort
      and physician/staff efficiency. The article deals with the flow of the patient,
      physician, staff, and materials through an efficient AEC. Detailed information of
      the design rules that must be followed and the entities that will review and
      license the AEC are included. The design of the AEC from the parking lot to the
      exit from the AEC is discussed. A complete space program is presented to help the
      reader determine the rooms in the center and the total area required for the
      center. The functional relationship diagram included in the article will help the
      reader understand the relationship of one room to another in the AEC. The
      philosophy behind the design and functional relationships is discussed in detail.

PMID- 12180152
TI  - Genetics Evaluation Guidelines for the Etiologic Diagnosis of Congenital Hearing
      Loss. Genetic Evaluation of Congenital Hearing Loss Expert Panel. ACMG statement.
AB  - The advent of hearing screening in newborns in many states has led to an increase
      in the use of genetic testing and related genetic services in the follow-up of
      infants with hearing loss. A significant proportion of those with congenital
      hearing loss have genetic etiologies underlying their hearing loss. To ensure
      that those identified with congenital hearing loss receive the genetic services
      appropriate to their conditions, the Maternal and Child Health Bureau of the
      Health Resources and Services Administration funded the American College of
      Medical Genetics to convene an expert panel to develop guidelines for the genetic
      evaluation of congenital hearing loss. After a brief overview of the current
      knowledge of hearing loss, newborn screening, and newborn hearing screening, we
      provide an overview of genetic services and a guideline that describes how best
      to ensure that patients receive appropriate genetic services. The significant
      contribution of genetic factors to these conditions combined with the rapid
      evolution of knowledge about the genetics of these conditions overlaid with the
      inherently multidisciplinary nature of genetic services provides an example of a
      condition for which a well-integrated multidisciplinary approach to care is
      clearly needed.

PMID- 12180154
TI  - Regulation and certification issues.
AB  - Regulatory and certification issues for endoscopy are complex, detailed, and
      broad. The different sources of the myriad regulations often have conflicting
      agendas, and the venues that seek to regulate endoscopic practice often overlap
      and seem redundant. Nonetheless, in spite of, or perhaps as a result of stringent
      regulation, endoscopy in the United States in thriving and continues to grow each
      year. Moreover, the penalties for not following the various regulations can be
      severe, and may result in criminal and civil sanctions. Any physician starting or
      already participating in a freestanding endoscopy center is well served by
      becoming familiar with the intent and generalities of each regulatory situation,
      and seeking appropriate legal and consulting counsel for specifics.

PMID- 12180155
TI  - Outpatient endoscopy. The case for the ambulatory surgery center.
AB  - Since the late 1970s, there has been a dramatic shift of GI endoscopy services
      from the inpatient to the outpatient setting. Outpatient GI endoscopy has
      migrated from the hospital endoscopy unit to the office and then on to the EASC.
      This evolution has been brought about by many forces, including the drive for
      health care cost containment, a desire for enhanced service, cost pressure on
      physicians, and demands for quality assurance. Although there are advantages and
      disadvantages to each of the outpatient settings (see Tables 5 and 6), the EASC
      seems to offer the most value to patients, payers, and physician owners. That
      value is defined as good outcomes, excellent service, and reasonable cost. Those
      attributes of the EASC that are most important in guaranteeing this value are
      physician control, time efficiency, convenience, and adequate reimbursement. The
      endoscopic ambulatory surgery center seems to be the best environment for
      delivering endoscopic services. The office AEC can only approach the
      attractiveness of an EASC when restrictive certificate-of-need laws prevent the
      development of an EASC; when groups lack a critical number of endoscopists to
      support an EASC (at least three endoscopists with a potential procedure volume of
      1200 to 1800 procedures per year [11]); when excess office capacity and personnel
      can be used for the office AEC; and, perhaps most importantly, when there is an
      ability to secure favorable contracts for facility payment from private health
      plans to the office endoscopy center. The evolution of EASCs over three decades
      has demonstrated many advantages to patients, physicians, and payers. Although
      further questions and challenges are inevitable, EASCs can adapt quickly and
      deliver value. The author believes the future is deservedly bright for such
      facilities.

PMID- 12180156
TI  - Assessing the financial health of the endoscopy center.
AB  - Just as a trend of a patient's physiologic vital signs is more informative than a
      single assessment, the most reliable measure of EASC financial health is achieved
      over a continuum of time. The earliest estimate of prognosis is accomplished with
      a business plan that is based on an analysis of practice history, strategic
      planning, and carefully derived assumptions. Periodic assessments of financial
      performance with benchmarking data provide a current assessment of health and
      allow trending of performance improvements or decline. Assurance of future
      financial health is derived from focusing on customer needs, developing EASC core
      competence, and creating value through innovation. Following these guidelines
      helps to ensure a strong, productive, and long-lasting EASC.

PMID- 12180157
TI  - Outpatient endoscopy possibilities for the office.
AB  - Office-based GI endoscopy is an alternative to more highly regulated EASC or
      hospital endoscopy units for physicians who are limited by Certificate of Need
      laws, group size, or other factors in developing an EASC. Such office-based
      endoscopy can successfully improve physician time management, patient
      satisfaction, and enhance practice revenues in selected patient populations.
      Safety and quality should be maintained at levels commensurate with hospital
      outpatient departments and EASCs.

PMID- 12180158
TI  - A corporate partner in the endoscopic ambulatory surgery center. A business
      relationship that works.
AB  - Although doubts persist in the minds of some, physician owners-developers of
      EASCs are increasingly entering into long-term business relationships with a CP
      by jointly developing an EASC or by selling a controlling financial interest in
      their EASC to the CP. In exchange, the physicians benefit through improved
      quality of care, increased patient and physician satisfaction, and enhanced EASC
      revenues.

PMID- 12180159
TI  - A corporate partner in the endoscopic ambulatory surgery center. Is it worth the
      cost?
AB  - In the preceding article of this two-part polemic on the advisability of a
      corporate partner in the endoscopic ambulatory surgery center (EASC), the
      advantages of such a partner were discussed and criteria given for judging its
      performance. Alternatives to the corporate partner were discussed. In that
      article, the corporate partnership in the EASC is a positive development yielding
      many benefits and few disadvantages to the physicians and the center. In this
      article, the balance tilts the other way.

PMID- 12180161
TI  - Staffing and scheduling in the endoscopy center.
AB  - As the growth of ambulatory endoscopy continues, the effort to deliver good
      clinical outcomes remains the primary goal. Achieving this goal is greatly
      impacted by the decisions made regarding staffing and scheduling. In addition to
      proven management techniques, creative thinking should also be used to allow for
      innovative and flexible ideas to be tried in the endoscopy unit. As more
      procedures are moved to the outpatient setting, greater scrutiny of patient care
      can be expected from outside agencies. Initial attention to details in addressing
      staffing and scheduling issues reaps significant benefits in developing and
      maintaining an efficient operation, and providing the quality of patient care
      desired by all interested parties.

PMID- 12180160
TI  - Endoscopic ambulatory surgery centers in the academic medical center. We can do
      it too!
AB  - A freestanding ambulatory surgery center (ASC) at an academic institution is an
      exception rather than the rule. It is a major challenge to the concept of the
      traditional academic medical center. Advantages and disadvantages are discussed,
      as well as the detailed planning process beginning with a well executed
      feasibility study, the hiring of consultants, and financing of the facility.
      Construction, opening of the facility and operation are not different from other
      ACSs. However, the integration of teaching and research presents new
      opportunities. Lessons learned and advice to others are detailed on how the ASC
      benefitted one specific institution and how it may add value and revenue to other
      academic medical centers.

PMID- 12180162
TI  - Sedation and analgesia.
AB  - In the United States sedation and analgesia is the standard of practice when
      performing upper and lower gastrointestinal endoscopy. Many of these endoscopic
      procedures are performed in ambulatory endoscopy centers, including ambulatory
      surgery centers. This article reviews new Joint Commission on Accreditation of
      Healthcare Organizations standards for sedation and analgesia, drugs used for
      sedation and analgesia (including side effects), patient assessment and
      monitoring (before, during, and postprocedure), and discharge of patients from
      the ambulatory endoscopy center.

PMID- 12180163
TI  - Information management.
AB  - The desire and requirements for information across the continuum of the
      enterprise are evident, because outcome measures, quality report cards, and
      financial pressures effect health care contracting. The real or perceived
      obstacles to having a comprehensive information management solution (the price
      tag, the compatibility of hardware and software, multiple locations, ownership of
      the information, and confidentiality) are so daunting that many are loathe to
      press ahead. The introduction of modern information technology into the AEC
      requires a systematic stepwise approach working with trusted partners and stable
      standards. Intelligent investment in these systems results in a more efficient
      and effective operating environment based on ongoing data monitoring.

PMID- 12180164
TI  - New technology in the endoscopy center.
AB  - The boundaries of endoscopy will continue to expand. Imaging modalities, such as
      high-resolution and high magnification endoscopy, tissue spectroscopy, optical
      coherence tomography, and wireless endoscopy, will continue to evolve. New
      therapeutic modalities, such as endoscopic antireflux procedures, are making
      endoscopic surgery a reality. In the increasingly restrictive reimbursement
      environment, however, it is critical to establish the cost-effectiveness of these
      new technologies to integrate them into daily practice.

PMID- 12180165
TI  - Coding and billing for gastrointestinal endoscopy.
AB  - The complexities associated with the coding, billing, and reimbursement process
      seem to increase daily. Keeping abreast of the changes in this environment is, to
      say the least, a challenge. To succeed in today's billing environment the
      gastroenterologist should surround his or her practice with staff, resources, and
      education. Experienced skilled staff, preferably a certified professional coder
      should be employed. Certified coders bring advanced coding skills to ones
      practice, which allows increased proficiency with the coding and billing process.
      Provide the necessary resources for staff. Current coding material is crucial to
      the financial success of the practice. CPT-4, ICD-9, and Correct Coding Guide are
      the bare basics of the resource material available to staff. Maintaining a
      library of resource material (i.e., Medicare bulletins, managed care newsletters,
      and so forth) aids the staff with the necessary tools to carry out their duties.
      In addition, specific gastroenterology coding subscriptions are available to
      assist in staying ahead of the ever-changing billing and coding environment.
      Continuing education in the billing and coding process for both the physician and
      staff is essential. Numerous workshops are offered periodically. It is imperative
      that staff attends all Medicare-sponsored workshops in addition to
      gastroenterology-specific coding seminars. More and more physicians are now aware
      of their responsibility in the billing process and have begun to participate in
      the coding education along with their staff. This is a significant indicator of a
      physicians' intent to have a compliant and financially successful practice.

PMID- 12180166
TI  - Continuous quality improvement in the ambulatory endoscopy center.
AB  - What does quality assessment have to do with the practicing gastroenterologist?
      Why should one spend the time and effort to incorporate CQI activities into an
      already busy practice? First and foremost, quality improvement should directly
      benefit the patient by ensuring that they receive the highest quality of care
      possible. For example, comparing endoscopic use or outcomes, such as procedure
      success or complications, with national standards or other endoscopists in the
      same community may identify physicians who could benefit from additional
      training. Similar analyses may likewise identify outstanding physicians who might
      serve as resources for other physicians. Surveys of patient satisfaction may
      reveal deficiencies, which might be unknown to a physician who is otherwise
      technically excellent; deficiencies that would never have been uncovered by
      traditional measures of quality. Second, applying the techniques of CQI to study
      one's own practice can provide a competitive edge when vying for managed care or
      corporate contracts. In this regard, CQI can be used to document physician or
      practice performance through tracking of endoscopic use, procedure success and
      complication rates, and patient satisfaction. Finally, the rising concern among
      various patient advocacy groups has led to an increased emphasis on quality
      improvement, and in most cases it is a required activity as part of the
      accreditation process. Steps to quality improvement There is more to quality
      improvement than simply selecting and implementing a performance improvement
      plan. A number of steps have been suggested to achieve fundamental improvement in
      the quality of medical care [3]. The first is to use outcomes management for
      improvement rather than for judgment. One of the major criticisms of QA is that
      it will be used to judge physicians providing care. It is feared that CQI will be
      used to identify poor performers who will then be punished. This strategy leads
      to fear and inhibits an honest pursuit of improvement. Second, learning must be
      viewed as a process. A quality improvement plan that is successful in one setting
      may not be as favorable in another situation. Clinicians must be able to focus on
      their individual situations and adapt what others have implemented to their own
      practice. Third, the most important aspect of the quality improvement is the
      implementation step. It matters little if elegant studies of endoscopic
      complications or patient satisfaction are completed if the information is not
      used to improve the delivery of health care to every single patient. The delivery
      of medical care continues to evolve. Resources are becoming increasingly scarce
      and the progressive rise of health care expenditures suggests a need for control.
      In this zeal for cost constraint, quality must not be sacrificed. This new-found
      attention to quality must be extended to the level of the individual practitioner
      to ensure that individual patients' interests are protected and the best possible
      care is delivered regardless of the economic implications. As providers of health
      care, endoscopists need to take an active role in these efforts both in
      understanding and implementing the techniques of quality assessment into their
      practices. If physicians are not actively involved in data collection and
      measurement to improve the quality and value of their own work, someone else will
      undoubtedly assume this role.

PMID- 12180167
TI  - Risk management for the endoscopy center.
AB  - Risk management, as applied to practice in the endoscopy center, is a framework
      of processes that attempt to minimize medical errors, prevent adverse events and
      patient injury, reduce the probability of malpractice actions being brought, and
      limit the financial and personal psychological costs that accompany malpractice
      lawsuits. This article summarizes the components of these processes, building on
      a foundation of applied legal concepts and pertinent malpractice claim data.

PMID- 12180168
TI  - Revenue enhancement for the practice and the endoscopic ambulatory surgery
      center.
AB  - Gastroenterologists, like all physicians, are attempting to control more of the
      services they provide by developing programs that enhance quality of care and
      practice revenues, reduce physician stress, and improve the physician's quality
      of life. Many opportunities exist to accomplish these goals, including those
      discussed in this article. The overriding feature of any such activity, however,
      must always meet the criteria of improving patient care.

PMID- 12180169
TI  - Clinical research.
AB  - Opportunities for clinical research should be explored carefully. Sites should
      evaluate potential areas of success, and focus on developing a quality center
      that can provide accurate data. Although there are numerous challenges to
      building a successful and productive research center, the rewards are great.

PMID- 12180170
TI  - A methodology for missile countermeasures optimization under uncertainty.
AB  - The missile countermeasures optimization problem is a complex strategy
      optimization problem that combines aircraft maneuvers with additional
      countermeasures in an attempt to survive attack from a single surface-launched,
      anti-aircraft missile. Classic solutions require the evading aircraft to execute
      specific sequences of maneuvers at precise distances from the pursuing missile
      and do not effectively account for uncertainty about the type and/or current
      state of the missile. This paper defines a new methodology for solving the
      missile countermeasures optimization problem under conditions of uncertainty. The
      resulting genetic programming system evolves programs that combine maneuvers with
      such countermeasures as chaff, flares, and jamming to optimize aircraft
      survivability. This methodology may be generalized to solve strategy optimization
      problems for intelligent, autonomous agents operating under conditions of
      uncertainty.

PMID- 12180171
TI  - Group properties of crossover and mutation.
AB  - It is supposed that the finite search space omega has certain symmetries that can
      be described in terms of a group of permutations acting upon it. If crossover and
      mutation respect these symmetries, then these operators can be described in terms
      of a mixing matrix and a group of permutation matrices. Conditions under which
      certain subsets of omega are invariant under crossover are investigated, leading
      to a generalization of the term schema. Finally, it is sometimes possible for the
      group acting on omega to induce a group structure on omega itself.

PMID- 12180172
TI  - ZCS redux.
AB  - Learning classifier systems traditionally use genetic algorithms to facilitate
      rule discovery, where rule fitness is payoff based. Current research has shifted
      to the use of accuracy-based fitness. This paper re-examines the use of a
      particular payoff-based learning classifier system--ZCS. By using simple
      difference equation models of ZCS, we show that this system is capable of optimal
      performance subject to appropriate parameter settings. This is demonstrated for
      both single- and multistep tasks. Optimal performance of ZCS in well-known,
      multistep maze tasks is then presented to support the findings from the models.

PMID- 12180173
TI  - Evolving neural networks through augmenting topologies.
AB  - An important question in neuroevolution is how to gain an advantage from evolving
      neural network topologies along with weights. We present a method, NeuroEvolution
      of Augmenting Topologies (NEAT), which outperforms the best fixed-topology method
      on a challenging benchmark reinforcement learning task. We claim that the
      increased efficiency is due to (1) employing a principled method of crossover of
      different topologies, (2) protecting structural innovation using speciation, and
      (3) incrementally growing from minimal structure. We test this claim through a
      series of ablation studies that demonstrate that each component is necessary to
      the system as a whole and to each other. What results is significantly faster
      learning. NEAT is also an important contribution to GAs because it shows how it
      is possible for evolution to both optimize and complexify solutions
      simultaneously, offering the possibility of evolving increasingly complex
      solutions over generations, and strengthening the analogy with biological
      evolution.

PMID- 12180174
TI  - Future solutions for the treatment and disposal of hazardous wastes in China.
AB  - The current status of the treatment and disposal of hazardous wastes in China is
      summarized on the basis of the results of the Declaring and Registration Project
      initiated nationally in 1995. A principle framework for the sound management of
      hazardous wastes is proposed, which includes three levels of technical solutions.
      Large-scale enterprises are encouraged to recycle, to treat, and to dispose of
      wastes by means of constructing facilities, and to have their extra capacities
      available to the public for a reasonable fee. Municipal governments, provincial
      governments, and the Central Government are to plan and construct centralized
      facilities to recycle, treat, and dispose of wastes. For a solution at the
      manufacturing level, recycling is identified as the main approach. Centralized
      facilities at the municipal level will mainly focus on special wastes that are
      unsuitable to transport and store, such as hospital waste, and for the technical
      solution at this level, incineration and recycling are identified as the main
      approaches. For the technical solution at the provincial and national levels,
      landfill and incineration are identified as the main approaches. Based on this
      principle and the current available data on hazardous wastes, a preliminary plan
      for the spatial distribution of cross-provincial centralized treatment and
      disposal facilities of hazardous wastes is presented. The construction of
      approximately nine cross-provincial comprehensive facilities is proposed. A
      priority list for the construction of these planned facilities is also presented.

PMID- 12180175
TI  - River systems as providers of goods and services: a basis for comparing desired
      and undesired effects of large dam projects.
AB  - In developing countries, large dam projects continue to be launched, primarily to
      secure a time-stable fresh-water supply and to generate hydropower. Meanwhile,
      calls for environmentally sustainable development put pressure on the dam
      building industry to integrate ecological concerns in project planning and
      decision-making. Such integration requires environmental impact statements (EISs)
      that can communicate the societal implications of the ecological effects in terms
      that are understandable and useful to planners and decision-makers. The purpose
      of this study is to develop a basic framework for assessing the societal
      implications of the river ecological effects expected of a proposed large dam
      project. The aim is to facilitate a comparison of desired and potential undesired
      effects on-site and downstream. The study involves two main tasks: to identify
      key river goods and services that a river system may provide, and to analyze how
      the implementation of a large dam project may alter the on-site capacity and
      downstream potentials to derive river goods and services from the river system.
      Three river goods and six river services are identified. River goods are defined
      as extractable partly man-made products and river services as naturally sustained
      processes. By four main types of flow manipulations, a large dam project improves
      the on-site capacity to derive desired river goods, but simultaneously threatens
      the provision of desirable river goods and services downstream. However, by
      adjusting the site, design, and operational schedule of the proposed dam project,
      undesirable effects on river goods and services can be minimized.

PMID- 12180176
TI  - Fertilizer management in watersheds of two Ramsar wetlands and effects on quality
      of inflowing water.
AB  - Two field experiments were carried out in the watersheds of two Ramsar wetland
      areas, Lakes Koronia and Volvi (area A) and Lakes Mikri and Megali Prespa (area
      B), to study the effect of application of N fertilizer on wheat yields, the
      quality of runoff water, and the quality of stream water. The treatments were a
      combination of two methods of fertilizer application (total amount in fall, and
      2/3 in fall + 1/3 in spring) at three rates (0, 100, and 200 kg N/ha) with four
      replications. Concentrations of NH4+, NO3-, NO2-, P, and Cl- and pH were
      determined in all water samples. Runoff water quality was not influenced by
      fertilizer application in either area. Chemical parameters for water did not
      differ along the selected watercourses in area B, while in area A they were
      higher in the samples taken near Lake Koronia than in the samples taken upstream,
      indicating that the watercourses are polluted downstream by nonagricultural
      sources. The differences in wheat yields between the 100 and 200 kg N/ha
      application rates were not high. These results call for better fertilizer
      management in order to achieve better yields and to diminish the possibility to
      have negative effects to the environment.

PMID- 12180177
TI  - Urban channel adjustments in a management context: an Australian example.
AB  - The impact of urbanization on stream channels has been investigated in a range of
      areas; the degree and extent of the channel adjustments have been demonstrated;
      and for a few areas these characteristics have recently been placed into a
      spatial context. A method of rapid field survey for depicting the channel network
      of urban areas in terms of near natural, adjusted, and channelized systems is
      illustrated for the urban area of Armidale NSW, for which Armidale Dumaresq
      Council had prepared a storm-water management plan. Such a survey could enable
      channel characteristics and adjustments, as well as water quantity and quality,
      to be included in the management plan. Possible options for management to address
      are suggested for each of the channel categories. A channel classification system
      of the kind suggested can provide a basic complement for the further development
      of the stormwater management plan, can afford a basis for specifying management
      alternatives, and can be helpful in demonstrating the options offered for
      community consultation.

PMID- 12180178
TI  - Sourcing sediment using multiple tracers in the catchment of Lake Argyle,
      Northwestern Australia.
AB  - Control of sedimentation in large reservoirs requires soil conservation at the
      catchment scale. In large, heterogeneous catchments, soil conservation planning
      needs to be based on sound information, and set within the framework of a
      sediment budget to ensure that all of the potentially significant sources and
      sinks are considered. The major sources of sediment reaching the reservoir, Lake
      Argyle, in tropical northwestern Australia, have been determined by combining
      measured sediment fluxes in rivers with spatial tracer-based estimates of
      proportional contributions from tributaries of the main stream entering the lake,
      the Ord River. The spatial tracers used are mineral particle magnetics, the
      strontium isotopic ratio, and the neodymium isotopic ratio. Fallout of 137Cs has
      been used to estimate the proportion of the sediment in Lake Argyle eroded from
      surface soils by sheet and rill erosion, and, by difference, the proportion
      eroded from subsurface soils by gully and channel erosion. About 96% of the
      sediment in the reservoir has come from less than 10% of the catchment, in the
      area of highly erodible soils formed on Cambrian-age sedimentary rocks. About 80%
      of the sediment in the reservoir has come from gully and channel erosion. A major
      catchment revegetation program, designed to slow sedimentation in the reservoir,
      appears to have had little effect because it did not target gullies, the major
      source of sediment. Had knowledge of the sediment budget been available before
      the revegetation program was designed, an entirely different approach would have
      been taken.

PMID- 12180179
TI  - A conceptual model for defining and assessing land management units using a fuzzy
      modeling approach in GIS environment.
AB  - Appropriate land management decisions are important for current and future use of
      the land to ensure its sustainability. This requires that land management units
      (LMUs) be specified to enable the identification of specific parameters employed
      in decision making processes. This paper presents the development of a conceptual
      model, within geographic information systems (GIS), for defining and assessing
      LMUs from available biophysical information. The model consists of two main
      components (sub-models): land quality-based suitability analysis and soil erosion
      estimation. Using a fuzzy set methodology, the first sub-model was constructed to
      derive a land suitability index (LSI) for a cropping land utilization type. The
      LSI thus highlights the suitability grades of every pixel in the study area on a
      continuous basis. A submodel of soil erosion was established based on the Revised
      Universal Soil Loss Equation (RUSLE) utilising the same spatial data bases
      employed for structuring the LSI. Using a soil loss tolerance principle, a fuzzy
      membership function of average annual soil loss (called soil loss index, SLI) was
      established, leading to compatibility between LSI and SLI for data integration.
      LMUs were then derived from various combinations of LSI and SLI. The methodology
      developed shows the significance of the model for refining available land
      suitability evaluation systems, which take no account of expected land
      degradation (from erosion) due to a nominated land use. It also provides a
      valuable guideline for cost-effective GIS applications in the identification and
      assessment of homogeneous land units, using available spatial information sets,
      at a finer scale.

PMID- 12180180
TI  - Foraging areas of king penguins from Macquarie Island in relation to a marine
      protected area.
AB  - Twenty-three king penguins (Aptenodytes patagonicus) from Macquarie Island were
      tracked by satellite during the late incubation period in 1998-1999 to determine
      the overlap of the foraging zone of king penguins with an area to be declared a
      marine protected area (MPA) near the island. While all penguins left the colony
      in an easterly direction and traveled clockwise back to the island, three
      penguins foraged in the northern parts of the general foraging area and stayed
      north of 56 degrees S. The remaining 20 penguins ventured south and most crossed
      59 degrees S before returning to the island. The total foraging area was
      estimated to be 156,000 km2 with 36,500 km2 being most important (where penguins
      spent > 150 hr in total). North-foraging penguins reached on average 331 +/- 24
      km from the colony compared to 530 +/- 76 km for the south-foraging penguins. The
      latter traveled an average total distance of 1313 +/- 176 km, while the northern
      foragers averaged 963 +/- 166 km. Not only did the penguins spend the majority of
      their foraging time within the boundaries of the proposed MPA, they also foraged
      chiefly within the boundaries of a highly protected zone. Thus, the MPA is likely
      to encompass the foraging zone of king penguins, at least during incubation.

PMID- 12180181
TI  - Soil arthropods (Coleoptera, Isopoda) in organic and conventional agroecosystems.
AB  - The relationship between two soil arthropod communities (Coleoptera and Isopoda)
      in organic and conventional fields was investigated. Soil arthropods were sampled
      by pitfall traps, and fuzzy set theory and canonical correspondence analysis
      (CCA) were used for their classification. The study was conducted in: (1) two
      organic and two conventional vineyards, (2) two organic and two conventional
      olive groves, and (3) one organic rotation system that involved maize and one
      conventional maize field. The species composition (three main fuzzy groups) was
      affected by the crop species and not by the farming system. The CCA placed the
      rare and unique taxa of soil arthropods at the edges of the diagram and grouped
      most of them together in relation to soil organic matter and Ca. The same
      analysis grouped all olive groves and related them to soil organic matter, all
      vineyards and related them to soil P and, finally, all maize fields and related
      them to soil N.

PMID- 12180182
TI  - Calculating resource restoration for an oil discharge in Lake Barre, Louisiana,
      USA.
AB  - Under the United States Oil Pollution Act of 1990, natural resource trustees are
      charged with assessing natural resource impacts due to an oil spill and
      determining the type and amount of natural resource restoration that will
      compensate the public for the impacts. Habitat equivalency analysis is a
      technique through which the impacts due to the spill and the benefits of
      restoration are quantified; both are quantified as habitat resources and
      associated ecological services. The goal of the analysis is to determine the
      amount of restoration such that the services lost are offset by services provided
      by restoration. In this paper, we first describe the habitat equivalency analysis
      framework. We then present an oil spill case from coastal Louisiana, USA, where
      the framework was applied to quantify resource impacts and determine the scale of
      restoration. In the Louisiana case, the trustees assessed impacts for oiled salt
      marsh and direct mortality to finfish, shellfish, and birds. The restoration
      project required planting salt-marsh vegetation in dredge material that was
      deposited on a barrier island. Using the habitat equivalency analysis framework,
      it was determined that 7.5 ha of the dredge platform should be planted as salt
      marsh. The planted hectares will benefit another 15.9 ha through vegetative
      spreading resulting in a total of 23.4 ha that will be enhanced or restored as
      compensation for the natural resource impacts.

PMID- 12180183
TI  - The National Vegetation Classification Standard applied to the remote sensing
      classification of two semiarid environments.
AB  - The National Vegetation Classification Standard (NVCS) was implemented at two US
      National Park Service (NPS) sites in Texas, the Padre Island National Seashore
      (PINS) and the Lake Meredith National Recreation Area (LMNRA), to provide
      information for NPS oil and gas management plans. Because NVCS landcover
      classifications did not exist for these two areas prior to this study, we created
      landcover classes, through intensive ground and aerial reconnaissance, that
      characterized the general landscape features and at the same time complied with
      NVCS guidelines. The created landcover classes were useful for the resource
      management and were conducive to classification with optical remote sensing
      systems, such as the Landsat Thematic Mapper (TM). In the LMNRA, topographic
      elevation data were added to the TM data to reduce confusion between cliff, high
      plains, and forest classes. Classification accuracies (kappa statistics) of 89.9%
      (0.89) and 88.2% (0.87) in PINS and LMNRA, respectively, verified that the two
      NPS landholdings were adequately mapped with TM data. Improved sensor systems
      with higher spectral and spatial resolutions will ultimately refine the broad
      classes defined in this classification; however, the landcover classifications
      created in this study have already provided valuable information for the
      management of both NPS lands. Habitat information provided by the classifications
      has aided in the placement of inventory and monitoring plots, has assisted oil
      and gas operators by providing information on sensitive habitats, and has allowed
      park managers to better use resources when fighting wildland fires and in
      protecting visitors and the infrastructure of NPS lands.

PMID- 12180184
TI  - Land-cover change in upper Barataria Basin estuary, Louisiana, 1972-1992:
      increases in Wetland area.
AB  - The Barataria Basin, Louisiana, USA, is an extensive wetland and coastal estuary
      system of great economic and intrinsic value. Although high rates of wetland loss
      along the coastal margin of the Barataria Basin have been well documented, little
      information exists on whether freshwater wetlands in the upper basin have
      changed. Our objectives were to quantify land-cover change in the upper basin
      over 20 years from 1972-1992 and to determine land-cover transition rates among
      land-cover types. Using 80-m resolution Landsat MSS data from the North American
      Landscape Characterization (NALC) data archive, we classified images from three
      time steps (1972, 1985, 1992) into six land-cover types: agriculture, urban,
      bottomland hardwood forest, swamp forest, freshwater marsh, and open water.
      Significant changes in land cover occurred within the upper Barataria Basin over
      the study period. Urban land increased from 8% to 17% of the total upper basin
      area, primarily due to conversions from agricultural land, and to a lesser
      degree, bottomland forest. Swamp forest increased from 30% to 41%, associated
      with conversions from bottomland hardwood forest and freshwater marsh. Overall,
      bottomland forest decreased 38% and total wetland area increased 21%. Within the
      upper Barataria, increases in total wetland area may be due to land subsidence.
      Based on our results, if present trends in the reduction of bottomland forest
      land cover were to continue, the upper Barataria Basin may have no bottomland
      hardwood forests left by the year 2025, as it is subjected to multiple stressors
      both in the higher elevations (from urbanization) and lower elevations (most
      likely from land subsidence). These results suggest that changes in the upper
      freshwater portions of coastal estuaries can be large and quite different from
      patterns observed in the more saline coastal margins.

PMID- 12180185
TI  - Change of Cu,Zn-superoxide dismutase activity of guinea pig lung in experimental
      asthma.
AB  - Correlation between the level of reactive oxygen species (ROS) generated by
      airway inflammatory cells and superoxide dismutase (SOD) activity of pulmonary
      tissue during an asthma attach was investigated in a guinea pig model of allergic
      asthma. In addition, the influence of SOD inhibition by diethyldithiocarbamate
      (DDC, Cu-chelating agent) on the airway was investigated in terms of pulmonary
      function during an asthma attach. Relative to controls, the capacity of
      bronchoalveolar lavage fluid (BAL) cells to release ROS was significantly
      increased in guinea pigs sensitized with ovalbumin (OA) as the antigen, and
      significantly increased in guinea pigs with an asthma attack provoked by the
      inhalation of OA. SOD activity was increased significantly in the antigen
      sensitized group. The asthma provocation group showed a tendency for increase in
      total SOD activity, compared with the sensitization group, whose increase was
      dependent on the increase in copper, zinc-SOD (Cu, Zn-SOD) activity. Pretreatment
      with DDC increased the severity and duration of the asthma attack. These results
      were indicated that Cu, Zn-SOD was closely involved in the asthma process,
      particularly in the scavenging of oxygen radicals secreted from BAL cells.

PMID- 12180186
TI  - Hemolysis of human erythrocytes by hypochlorous acid is modulated by amino acids,
      antioxidants, oxidants, membrane-perforating agents and by divalent metals.
AB  - The optimal conditions under which hypochlorous acid (NaOCl) either hemolyzes
      human RBC or kills monkey kidney epithelial cells (BGM) in culture had been
      investigated. While in Hank's balanced salt solution (HBSS), micromolar amounts
      of NaOCl caused full hemolysis and also killed BGM cells, in D-MEM or RPMI media
      rich in amino acids, 25-40 mM of hypochlorite were needed to induce cell injury.
      Cells exposed to high amounts of NaOCl became highly refractory to strong
      detergents. Hemolysis by NaOCl was strongly inhibited by a large variety of
      antioxidants. RBC treated by subtoxic concentrations either of peroxide, peroxyl
      radical, NO, cholesterol, PLA2, PLC as well as by N2, argon or by mixture of CO2
      (10%) and O2 (90%) became much more susceptible to lysis by NaOCl. On the other
      hand, while RBC treated by Fe2+, Co2+, and V2+ and to a lesser extent with Cu2+
      became highly resistant to NaOCl hemolysis presumably due to NaOCl decomposition,
      no such effect was found either with Co2+ or by Mn2+. RBC treated by azide to
      destroy catalase and then incubated with peroxide and with NaOCl failed to
      undergo hemolysis due to the ability of peroxide to decompose NaOCl. The
      inhibitory effects of the divalent metals on NaOCl-induced hemolysis were also
      substantiated by measuring the decrease in pH and by cyclic voltammetry. The
      findings that like peroxide, NaOCl also synergizes with membrane-perforating
      agents and with a protease to kill epithelial cells further implicate such
      "cocktails" in cell injury in inflammatory conditions. Taken together, because of
      the capacity of many agents to scavenge NaOCl, tissue damage by NaOCl-generated
      neutrophils can take place primarily if activated neutrophils closely adhere to
      target cells to avoid the scavenging effects of amino acids and of antioxidants.
      Therefore, the significance of the data which had tested the cytotoxic effects of
      NaOCl using cells suspended only in salt solutions, should be reconsidered.

PMID- 12180187
TI  - The interaction of resveratrol with ferrylmyoglobin and peroxynitrite; protection
      against LDL oxidation.
AB  - Resveratrol (3,4',5-trihydroxystilbene) is a natural phytoalexin synthesized in
      response to injury or fungal attack, found in the grape skin and wine, specially
      red wine. A large number of studies have demonstrated that resveratrol regulates
      many biological activities, namely protection against atherosclerosis by a set of
      pharmacological properties, including the antioxidant activity. In this study, we
      explored the capacity of resveratrol in protecting low density lipoproteins (LDL)
      against either ferrylmyoglobin- or peroxynitrite-mediated oxidation and the
      underlying mechanisms of its antioxidant potential. Resveratrol efficiently
      decreases the accumulation of hydroperoxides in LDL promoted by ferrylmyoglobin,
      a potent oxidant formed by the reaction of metmyoglobin with hydrogen peroxide,
      in a concentration-dependent manner, promptly reducing the oxoferryl complex to
      metmyoglobin. Simultaneously, resveratrol is consumed as detected by the rapid
      decrease in the characteristic peak at 310 nm, in a similar way to that observed
      upon its reaction with peroxidase/H2O2, pointing to a mechanism of one-electron
      oxidation and subsequent resveratrol dimer formation. On the other hand,
      resveratrol inhibits LDL apoprotein modifications induced by peroxynitrite,
      another potent oxidant formed by the reaction between superoxide and nitric
      oxide, as assessed by the decrease in apo-B net charge alterations and in
      carbonyl groups formation mediated by that oxidant. Resveratrol also interacts
      with peroxynitrite in a similar way to that observed with laccases, suggesting a
      mechanism of resveratrol oxidation rather than a nitration one. These mechanisms
      are discussed. Considering that either ferrylmyoglobin or peroxynitrite are
      physiologically relevant oxidants implicated in several pathologies, including
      atherosclerosis, our results certainly contribute to the understanding of the
      antioxidant action of resveratrol and consequently provide a new approach for the
      cardiovascular benefits associated with moderate consumption of red wine.

PMID- 12180188
TI  - Paraquat-generated oxidative stress in rat liver induces heme oxygenase-1 and
      aminolevulinic acid synthase.
AB  - The in vivo effect of the known herbicide, paraquat, on both hepatic oxidative
      stress and heme metabolism was studied. A marked increase in lipid peroxidation
      and a decrease in reduced glutathione (GSH) content were observed 1 h after
      paraquat administration. The activity of liver antioxidant enzymes, superoxide
      dismutase, catalase and glutathione peroxidase was decreased 3 h after paraquat
      injection. Heme oxygenase-1 induction started 9 h after treatment, peaking at 15
      h. delta-aminolevulinic acid synthase induction occurred once heme oxygenase had
      been enhanced, reaching its maximum (1.5-fold of control) at 16 h. delta
      aminolevulinic acid dehydratase activity was 40% inhibited at 3 h showing a
      profile similar to that of GSH, while porphobilinogenase activity was not
      modified along the whole period of the assay. Administration of alpha-tocopherol
      (35 mmol/kg body weight) 2 h before paraquat treatment entirely prevented the
      increase in thiobarbituric acid reactive substances (TBARS) content, the decrease
      in GSH levels as well as heme oxygenase-1 and delta-aminolevulinic acid synthase
      induction. This study shows that oxidative stress produced by paraquat leads to
      an increase in delta-aminolevulinic acid synthase and heme oxygenase-1
      activities, indicating that the herbicide affects both heme biosynthesis and
      degradation.

PMID- 12180189
TI  - Production of hydroxyl free radical in the xanthine oxidase system with addition
      of 1-methyl-3-nitro-1-nitrosoguanidine.
AB  - We have examined the mechanism of 1-methyl-3-nitro-1-nitrosoguanidine (MNNG)
      induced gastric cancer with respect to the production of hydroxyl free radical
      (OH). Nucleophilic attack by H2O2 on the nitroso group of MNNG produces 1-methyl
      3-nitroguanidine (MNG) and the intermediate peroxynitric acid (ONOOH), which
      splits into hydroxyl free radical (OH) and nitrogen dioxide leading to the
      formation of nitric and nitrate ions in water. Xanthine oxidase (XO) induces the
      production of O2.- or H2O2 from molecular oxygen, depending on the overall level
      of enzyme reduction. In this study, we examined OH production by the reaction of
      MNNG with H2O2 derived from the XO-HX system containing XO and the purine
      substrate hypoxanthine by ESR using the spin trapping reagent 5,5'-dimethyl-1
      pyrroline-N-oxide (DMPO). OH was produced in the XO-HX-DMPO system with addition
      of MNNG (the MNNG-XO-HX-DMPO system) under aerobic conditions, but was not in the
      XO-HX-DMPO system, and production of OH was inhibited by catalase but not by
      superoxide dismutase, suggesting that OH was produced by the reaction of MNNG
      with H2O2 derived from the XO-HX system. The production of OH was significantly
      increased with increase in the reducing activity of XO, though that of O2.- was
      not, also suggesting the O2(.-)-independent .OH production. The productions of
      nitrite ion and MNG in the MNNG-XO-HX system were determined by the colorimetric
      method and HPLC, respectively. Based on these findings, we conclude that .OH was
      produced by homolytic split of the intermediate ONOOH formed by nucleophilic
      attack of H2O2 derived from the XO-HX system on MNNG.

PMID- 12180190
TI  - Comparison of results from different laboratories in measuring 8-oxo-2'
      deoxyguanosine in synthetic oligonucleotides.
AB  - The European Standards Committee on Oxidative DNA Damage (ESCODD) was set up in
      1997 to resolve methodological problems and to reach agreement on the basal level
      of 8-oxo-2'-deoxyguanosine (8-oxodG) in biological samples. In the present ESCODD
      trial 6 samples of 8-oxodG-containing oligonucleotides with different ratios of 8
      oxodG/2'-deoxyadenosine (dAdo) were sent to 25 laboratories throughout Europe.
      The methods used were HPLC with electrochemical detection (amperometric or
      coulometric), GC-MS or LC-MS-MS. The LC-MS-MS and the coulometric HPLC analyses
      gave 8-oxodG concentrations within 53 and 73% of expected values, respectively,
      whereas the amperometric HPLC and GC-MS consistently overestimated the 8-oxodG
      concentration by several fold. As the oligonucleotides contained no 2'
      deoxyguanosine (dGuo), this was not due to artificial oxidation. On the contrary,
      in most cases the concentrations of dAdo and thymidine (dThd), used as estimates
      for non-oxidised DNA bases were underestimated, though a few laboratories
      overestimated the lowest concentration samples containing 8 and 20 microM,
      respectively. In one-third of the reported results, the ratio of 8-oxodG/10(5)
      dAdo was within 25% of the calculated value in the oligonucleotide samples and in
      half of the results the coefficient of variation in duplicate samples was less
      than 10%. The coefficients of variation were higher for the dAdo concentrations
      than for 8-oxodG. Our findings strongly indicate that careful quality control
      must be applied to the analytical procedures for 8-oxodG and very importantly
      also to the procedures for non-modified 2'-deoxyribonucleosides. We recommend the
      use of synthetic oligonucleotides for this purpose.

PMID- 12180191
TI  - Effect of chronic ethanol feeding on oxysterols in rat liver.
AB  - It was our hypothesis that, as a consequence of increased oxidative stress,
      cholesterol-derived hydroperoxides and oxysterols are increased in livers of rats
      exposed to ethanol. To test this we dosed Wistar rats (approximately 0.1 kg
      initial body weight) with ethanol chronically (rats fed a nutritionally complete
      liquid diet containing ethanol as 35% of total calories; sampled liver at
      approximately 6-7 weeks). We measured concentrations of 7 alpha- and 7 beta
      hydroperoxycholest-5-en-3 beta-ol (7 alpha-OOH and 7 beta-OOH) as well as 7 alpha
      and 7 beta-hydroxycholesterol (7 alpha-OH and 7 beta-OH), and 3 beta
      hydroxycholest-5-en-7-one (also termed 7-ketocholesterol; 7-keto). In response to
      chronic alcohol feeding, there were significant elevations in the concentrations
      of 7 alpha-OOH (+169%, P = 0.005) and 7 beta-OOH (+199%, P = 0.011). Increases in
      the concentrations of hepatic 7-keto (+74%, P = 0.01) and decreases in
      cholesterol (-43%; P = 0.03) also occurred. In contrast, the concentrations of
      both 7 alpha-OH and 7 beta-OH were not significant (NS). However, when oxysterols
      in chronic ethanol-fed rats were expressed relative to cholesterol there were
      significant increases in 7-keto/cholesterol (P = 0.0006), 7 alpha-OH/cholesterol
      (P = 0.0018) and 7 beta-OH/cholesterol (P = 0.0047). In conclusion, this is the
      first report of increased 7 alpha-OOH, 7 beta-OOH, and 7-keto in liver of rats
      and their elevation in chronic experimental alcoholism represent evidence of
      increased oxidative stress.

PMID- 12180192
TI  - Hydroxylation of deoxyguanosine at 5' site of GG and GGG sequences in double
      stranded DNA induced by carbamoyl radicals.
AB  - Free radicals generated by chemicals can cause sequence-specific DNA damage and
      play important roles in mutagenesis and carcinogenesis. Carbamoyl group (CONH2)
      and its derived groups (CONR2) occur as natural products and synthetic chemical
      compounds. We have investigated the DNA damage by carbamoyl radicals .(CONH2),
      one of carbon-centered radicals. Electron spin resonance (ESR) spectroscopic
      study has demonstrated that carbamoyl radicals were generated from formamide by
      treatment with H2O2 plus Cu(II), and from azodicarbonamide by treatment with
      Cu(II). We have investigated sequence specificity of DNA damage induced by
      carbamoyl radicals using 32P-labeled DNA fragments obtained from the human c-Ha
      ras-1 and p53 genes. Treatment of double-stranded DNA with carbamoyl radicals
      induced an alteration of guanine residues, and subsequent treatment with
      piperidine or Fpg protein led to chain cleavages at 5'-G of GG and GGG sequences.
      Carbamoyl radicals enhanced Cu(II)/H2O2-mediated formation of 8-oxo-7,8-dihydro
      2'-deoxyguanosine (8-oxodG) in double-stranded DNA more efficiently than that in
      single-stranded DNA. These results shows that carbamoyl radicals specifically
      induced hydroxylation of deoxyguanosine at 5' site of GG and GGG sequences in
      double-stranded DNA.

PMID- 12180193
TI  - A simple and rapid method for the determination of "free" iron in biological
      fluids.
AB  - We present a convenient method for determining "free" or non-protein-bound iron
      in biological fluids. The new method is based on the bathophenantroline method
      for determination of total serum iron, and comprises binding of iron by a
      chromogenic chelator (bathophenantroline-disulphonate, BPS), which is specific
      for ferrous iron. The ferrous complex of BPS absorbs strongly at 535 nm, and the
      detection limit is less than 1 microM in a sample size of 50 microliters. The
      chelator does not liberate iron from either haemoglobin or transferrin.
      Interference from copper or zinc in concentrations up to 50 microM does not
      significantly disturb measurements. The main problem when measuring in blood
      plasma, the high and fluctuating background in the region around 535 nm, has been
      overcome through filtering techniques. Data from measurements of ferrous iron in
      microdialysate, cerebrospinal fluid, and blood plasma in different animal models
      and clinical conditions are presented as illustrative examples of the usefulness
      of the method. The method allows the determination of ferric, as well as ferrous,
      iron in the same sample.

PMID- 12180194
TI  - Free radical scavenging properties of sulfinpyrazone.
AB  - Sulfinpyrazone, a potent uricosuric drug, was tested in vitro for its scavenging
      action against oxygen free radicals. In this study, sulfinpyrazone was able to
      scavenge 1,1-diphenyl-2-picrylhydrazyl radical with IC50 value of 29.82
      micrograms/ml compared to butylated hydroxytoluene (BHT, IC50 value = 20.15
      micrograms/ml) and Trolox (IC50 value = 16.01 micrograms/ml). It was able to
      scavenge superoxide anion with IC50 value of 27.72 micrograms/ml compared to
      Trolox (IC50 value = 22.08 micrograms/ml) and ascorbic acid (IC50 value = 14.65
      micrograms/ml). The hydroxyl radical scavenging activity of sulfinpyrazone is in
      a concentration-dependent fashion. In the range of concentrations used,
      sulfinpyrazone was not a scavenger toward H2O2. However, the intracellular H2O2
      induced 2',7'-dichlorofluorescin diacetate (DCF-DA) fluorescence in HL-60 cells
      was significantly reduced by sulfinpyrazone during 30-60 min of incubation.
      Finally, phorbol-12-myristate-13-acetate induced-lucigenin chemiluminescence in
      whole blood was markedly inhibited by sulfinpyrazone. Our results suggest a new
      direction for the pharmacological actions of sulfinpyrazone in free radical
      scavenging properties.

PMID- 12180195
TI  - The neuroprotective antioxidant alpha-lipoic acid induces detoxication enzymes in
      cultured astroglial cells.
AB  - alpha-Lipoic acid (LA), an antioxidant with broad neuroprotective capacity, is
      thought to act by scavenging reactive oxygen species and stimulation of
      glutathione synthesis. LA shows structural resemblance to dithiolethiones, like
      anethole dithiolethione (ADT). ADT protects against oxidative damage, primarily
      by induction of phase II detoxication enzymes, in particular NAD(P)H:quinone
      oxidoreductase (NQO1) and glutathione-S-transferase (GST). Therefore, we
      investigated whether LA, like ADT, is capable also of inducing these protective
      enzymes. Our data show that LA, like ADT, induces a highly significant, time- and
      concentration dependent, increase in the activity of NQO1 and GST in C6
      astroglial cells. The LA or ADT mediated induction of NQO1 was further confirmed
      by quantitative PCR and western blot analysis. This work for the first time
      unequivocally demonstrates LA mediated upregulation of phase II detoxication
      enzymes, which may highly contribute to the compounds' neuroprotective potential.
      Moreover, the data support the notion of a common mechanism of action of LA and
      ADT.

PMID- 12180196
TI  - alpha-tocopherol increases the intracellular glutathione level in HaCaT
      keratinocytes.
AB  - alpha-Tocopherol is a lipophilic vitamin that exhibits an antioxidative activity.
      The purpose of this study was to clarify the roles of alpha-tocopherol in the
      regulation of intracellular glutathione (GSH) levels in HaCaT keratinocytes. When
      HaCaT keratinocytes were cultivated with alpha-tocopherol for 24 h, the
      intracellular GSH was increased at every concentration of alpha-tocopherol
      tested. Furthermore, the HaCaT keratinocytes cultured with alpha-tocopherol at 50
      microM for 24 h exhibited resistance against H2O2. However, a short exposure of
      HaCaT keratinocytes to alpha-tocopherol for 1 h did not influence either the GSH
      level or the resistance to H2O2. These findings suggest that GSH, which is
      inductively synthesized by alpha-tocopherol, effectively reduces exogenous
      oxidative stress. To evaluate the effect of alpha-tocopherol on the GSH level,
      BSO, which is a typical inhibitor of gamma-glutamylcysteine synthetase (gamma
      GCS), was used. When BSO was added to HaCaT keratinocytes, no action of alpha
      tocopherol on the GSH level was observed. On the other hand, alpha-tocopherol
      resulted in the up-regulation of gamma-GCS-HS (heavy subunit) mRNA. In addition,
      water soluble alpha-tocopherol derivatives (alpha-tocopherol phosphate and
      trolox) caused no changes in GSH level. From these results, it was concluded that
      alpha-tocopherol increases the intracellular GSH level of HaCaT keratinocytes
      through the up-regulation of gamma-GCS-HS mRNA.

PMID- 12180197
TI  - In vitro antioxidant profile of phenolic acid derivatives.
AB  - Several caffeic acid esters isolated from propolis exhibit interesting
      antioxidant properties, but their in vivo use is compromised by hydrolysis of the
      ester bond in the gastrointestinal tract. Therefore, a series of caffeic acid
      amides were synthesized and their in vitro antioxidant profile was determined. A
      series of hydroxybenzoic acids, hydroxycinnamic acids, and the synthesized
      caffeic acid amides were tested for both their 1,1-diphenyl-2-picrylhydrazyl
      (DPPH) free radical scavenging and microsomal lipid peroxidation-inhibiting
      activity. Some of the highly active antioxidants were further tested by means of
      electron paramagnetic resonance for their hydroxyl radical scavenging activity.
      Since a promising antioxidant compound should show a lipid peroxidation
      inhibiting activity at micromolar level and a low cytotoxicity, the cytotoxicity
      of the phenolic compounds was also studied. In all the assays used, the caffeic
      acid anilides and the caffeic acid dopamine amide showed an interesting
      antioxidant activity.

PMID- 12180198
TI  - The mechanism of action of zinc-histidine complex (Curazink) as an antioxidant.

PMID- 12180199
TI  - The effect of growth of nasopharyngeal structures in velopharyngeal closure in
      patients with repaired cleft palate and controls without clefts: a cephalometric
      study.
AB  - To clarify the changes with growth of nasopharyngeal structures involved in
      velopharyngeal closure, a cross-sectional study from early childhood to puberty
      was carried out in 61 patients with repaired unilateral cleft lip and palate
      showing complete velopharyngeal closure (cleft group) and 82 controls without
      clefts (control group). Measurements of the nasopharyngeal area were derived from
      a coordinate system and landmarks on lateral cephalograms, and results were
      analysed by multivariate analysis and t test. The adequate ratio (velar length to
      pharyngeal depth ratio) in the control group was maintained at a stable value,
      indicating that the ratio around 1.3 would be standard to maintain velopharyngeal
      closure. The vertical position of posterior maxilla, pharyngeal depth and velar
      length in the cleft group showed a different pattern of growth from those in the
      control group. There was, however, characteristic growth in both groups for
      maintenance of velopharyngeal closure.

PMID- 12180200
TI  - Immediate alveolar ridge distraction after tooth extraction--a preliminary
      report.
AB  - Seven patients with severe periodontitis that had resulted in loss of alveolar
      ridge bone were treated by tooth extraction followed by immediate insertion of an
      implant distraction device. After successful distraction and bony healing the
      implant was used to fit a prosthesis.

PMID- 12180201
TI  - Regeneration of the mandibular condyle after unilateral condylectomy and myotomy
      of the masseter in lambs.
AB  - We investigated the degree of regeneration of the mandibular condyle after
      unilateral condylectomy and myotomy of the masseter in growing lambs. Four 10
      week-old lambs had unilateral condylectomy and myotomy of the superficial layer
      of the masseter on the right side, and were killed 3 months later. The joints
      were examined radiologically and histologically. All joints showed poor
      regeneration of the condylar head. In the medial plane there was partial condylar
      and articular cartilage reformation, but in the lateral plane there was neither
      condylar nor cartilaginous reformation. The articular cartilage of the temporal
      bone was thicker in the medial plane and the disc was thicker in the central
      plane, than in unoperated joints. We conclude that unilateral condylectomy and
      myotomy of the masseter in the growing period results in poor regeneration of the
      condyle.

PMID- 12180202
TI  - Insertion of percutaneous endoscopic gastrostomy tubes by a maxillofacial
      surgical team in patients with oropharyngeal cancer.
AB  - This study assessed the clinical outcome after insertion of a percutaneous
      endoscopic gastrostomy tube (PEGT) by a maxillofacial team in a series of 54
      patients. The indication for PEG feeding was any patient with oropharyngeal
      cancer who was unlikely to return to oral feeding within 14 days. Fifty-two
      patients (96%) had tubes successfully inserted at the time of examination under
      anaesthesia (n = 19) or definitive operation (n = 33). Feeding was established at
      a median of 2 days (range 1-6). Median duration of tube feeding was 18 weeks
      (range 4-70). There were no deaths or major complications and 10 minor
      complications. No tube was lost or required premature removal. We conclude that
      insertion of a PEG tube is a procedure that can be done safely by maxillofacial
      surgeons.

PMID- 12180203
TI  - Implantation of oral squamous cell carcinoma at the site of a percutaneous
      endoscopic gastrostomy: a case report.
AB  - A 55-year-old man had an operation and radiotherapy for a squamous cell carcinoma
      of the oral cavity and developed a metastatic deposit at the site of a
      percutaneous endoscopic gastrostomy, with no other evidence of systemic spread.
      Treatment of the metastasis was by neo-adjuvant chemotherapy with cisplatin and 5
      fluorouracil (5-FU) followed by en bloc resection of the stomal recurrence on the
      anterior abdominal wall. There has been no evidence of recurrence to date. Only
      17 other cases of metastasis to this site from a primary tumour in the upper
      aerodigestive tract have been reported. We review the relevant publications and
      discuss the techniques, complications and possible mechanisms of spread and their
      implications for the use of percutaneous endoscopic gastrostomy in head and neck
      cancer surgery.

PMID- 12180204
TI  - Bone induction in subcutaneous tissue in rats by a newly developed DNA-coated
      atelocollagen and bone morphogenetic protein.
AB  - A unique biomaterial, a mixture of DNA and collagen (DNA/collagen), was developed
      and its efficacy as a carrier matrix for bone morphogenetic protein (BMP) was
      evaluated histologically. The material was prepared as a composite of DNA from
      salmon milt and pepsin-digested type I collagen (atelocollagen) from bovine
      dermis. Phase-contrast and fluorescence microscopy showed atelocollagen fibres
      with DNA coating. The dose-response and time-course of bone induction by BMP in
      DNA/collagen (5 x 10 x 1 mm) in the subcutaneous tissue was investigated in 20
      male Wistar rats. The BMP/DNA/collagen induced new bone in a dose-dependent
      manner (0, 25, 50 or 100 micrograms of BMP). Histological examination in the time
      course study showed that the BMP (100 micrograms)/DNA/collagen induced bone
      formation, while the DNA/collagen alone resulted in the accumulation of
      fibroblasts. These results indicate that the DNA/collagen is effective as a
      carrier matrix for BMP. It provides a cell anchorage for differentiation of
      osteoblasts and is absorbed as bone matures.

PMID- 12180205
TI  - Modification of the Branemark irrigation system for use in free tissue transfer.

PMID- 12180206
TI  - Treatment of chylous fistula with fibrin glue and clavicular periosteal flap.
AB  - We describe a new treatment for chylous fistula using fibrin glue and clavicular
      periosteal flap.

PMID- 12180207
TI  - Changing picture of facial fractures in northern Nigeria.
AB  - This was a prospective study that aimed to find out the current pattern of facial
      fractures in northern Nigeria and to see if changes in the socioeconomic
      conditions in Nigeria during the past 20-30 years have affected the aetiology,
      sex and age distribution of the patients, and type of facial fractures. The
      setting was the maxillofacial unit of the University of Maiduguri Teaching
      Hospital, which is the only referral centre for facial trauma in north-eastern
      Nigeria, serving a population of about 30 million people. All 306 patients were
      treated for facial fracture between January 1996 and December 1999. Most of the
      patients (126/306, 41%) were in the age range 21-30 years and the male to female
      ratio was 2.19:1. The main causes of the fractures were assault (n = 147, 48%)
      followed by road traffic accidents (n = 111, 36%). Other aetiological factors
      such as falls, and sports or industrial accidents accounted for the remaining
      cases. Of the assault-related injuries 102 (33%) were the result of armed robbery
      and 45 (15%) the result of fights, mainly on the farms. The mandible was the most
      common site of fractures (n = 273, 89%) and most of the mandibular fractures were
      in the body of the mandible. Only 44/306 patients (14%) reported to the hospital
      within the first 24 hours after injury. Changing socioeconomic conditions are
      associated with an increase in assault-related facial fractures, but the
      predominantly affected age group, sex and site of fracture remain relatively
      constant.

PMID- 12180208
TI  - Long-term functional outcome of mandibular reconstruction with stainless steel AO
      reconstruction plates.
AB  - Mandibular continuity defects are usually reconstructed with bone grafts.
      However, factors associated with the tumour and the patient can still be reasons
      to choose reconstruction plates. The aim of this study was to find out the
      results of mandibular reconstructions with stainless steel AO reconstruction
      plates after a long follow-up period. The records of 36 patients were reviewed
      for personal data and the history of disease, treatment and complications.
      Patients with failed reconstructions were compared with those in whom the
      procedure had been successful. Patients and surgeons gave their opinion on the
      functional and cosmetic results. The mean follow-up was 39 months (range 4-99); 4
      patients were withdrawn because they developed early recurrent disease and in 17
      patients the reconstruction failed. We found no significant differences between
      the successful and the failed group. Fourteen patients could be evaluated for
      functional outcome, 10 of whom were totally or satisfactorily rehabilitated.
      Therefore, stainless steel reconstruction plates can be used in patients when
      other options are inappropriate.

PMID- 12180209
TI  - Ultrasonic debridement of contaminated facial wounds.
AB  - Contaminated facial wounds can be debrided with the Piezon ultrasonic scaler. The
      fine scaler tip provides efficient, rapid, precise and thorough removal of
      ingrained subdermal dirt and grit without the loss of viable facial tissue.

PMID- 12180210
TI  - A new type of occlusal wafer for orthognathic surgery.

PMID- 12180211
TI  - Intraoperative ultrasound-guided retrieval of an airgun pellet from the tongue: a
      case report.
AB  - Real-time intraoperative ultrasonography was used to detect and facilitate
      removal of an airgun pellet from the tongue of a 14-year-old boy. Diagnostic
      ultrasound was crucial in clarifying the positional relation between the foreign
      body and the instrument used, enabling safe, precise and rapid retrieval during a
      potentially hazardous surgical operation.

PMID- 12180212
TI  - Accuracy of diagnosis of fractures by maxillofacial and accident and emergency
      doctors using plain radiography compared with a telemedicine system: a
      prospective study.
AB  - Ten facial radiographs with fractures and 10 without fractures were viewed by
      eight oral and maxillofacial surgery (OMFS) and eight accident and emergency
      (A&E) doctors who were each asked questions about the presence and site of any
      fractures as well as the quality of the images and diagnostic confidence. Each
      radiograph was then transmitted over a teleradiology link and viewed by the same
      OMFS doctors who answered the same questions. The position of the fracture was
      more accurately assessed using plain radiography. Diagnosis by OMFS doctors using
      telemedicine was broadly comparable with fracture diagnosis by A&E doctors using
      plain radiography. Poor quality radiographs and frontozygomatic and infraorbital
      rim fractures were poorly diagnosed by telemedicine. This telemedicine system was
      a useful tool to aid diagnosis of most facial fractures. The need for appropriate
      clinical information is vital. Diagnosis of frontozygomatic and infraorbital rim
      disruption using telemedicine is less reliable than plain radiography.

PMID- 12180213
TI  - Paradental cysts: a role for food impaction in the pathogenesis? A review of
      cases from Northern Ireland.
AB  - We present the clinical, radiographic and histological findings of 15 paradental
      cysts. These were the second most common type of cyst associated with mandibular
      third molars, comprising 25% of all lesions at this site. Ten patients were aged
      30 years or younger and 13 gave a history of pericoronitis. There was a close
      relationship between the site of the cyst and the angle of the impacted tooth;
      the cyst lay mesially to two mesioangularly impacted teeth, buccal to two
      vertically impacted teeth and distal/distobuccal to the remainder, all but one of
      which were distoangular in impaction. The pericoronal follicular space was
      preserved in nine cases, a useful diagnostic sign. Most cysts were lined with
      epithelium that resembled that seen in radicular cysts, although the lining of
      three cysts resembled that of unicystic ameloblastoma, a potential diagnostic
      pitfall. We propose that the relation between location of cyst and angle of
      impaction points to a role for food impaction in the pathogenesis of paradental
      cysts.

PMID- 12180214
TI  - Angioleiomyoma in the tonsil: an uncommon tumour in a rare site.
AB  - An angioleiomyoma was excised from the palatine tonsil in a 30-year-old woman who
      complained of a painless swelling in the region of the tonsil. The mucosa
      covering the lesion showed prominent dilated blood vessels, necessitating
      vascular laboratory investigations to exclude any possibility of an aneurysm
      arising from the carotid system. The mass was excised with little blood loss.
      This was an uncommon tumour in an unusual site and required radio-imaging and
      angiographic studies of the great vessels of the head and neck before any
      operation was attempted. To the best of our knowledge, this is the first case
      reported in English.

PMID- 12180215
TI  - Foreign body reaction to calcium alginate fibre mimicking recurrent tumour of the
      submandibular salivary gland.
AB  - A 50-year-old woman was referred after the discovery of adenoid cystic carcinoma
      in an excised left submandibular gland. Treatment involved clearance of the left
      submandibular fossa, and bilateral levels II and III selective neck dissections.
      A left-sided submandibular haematoma developed during the immediate postoperative
      period. After removal of the clot, there was a persistent, low volume capillary
      ooze from the left submandibular fossa and a calcium alginate fibre pack
      (Kaltostat) was left in place to control the bleeding. After an extended period
      of time the pack excited a foreign body reaction which, on a computed tomogram,
      mimicked a recurrence of the tumour. We review the role of Kaltostat in this
      setting and its potential for foreign body reaction, which may mimic serious
      disease.

PMID- 12180216
TI  - Bilateral eyelid necrosis as a complication of pseudomonal septicaemia.
AB  - We present a case of bilateral eyelid necrosis as a result of Pseudomonas
      aeruginosa infection. This is a rare condition that occurs only in neutropenic
      patients. It may be unilateral or bilateral and requires aggressive management
      with correction of the neutrophil count, local debridement and systemic
      antibiotic therapy.

PMID- 12180217
TI  - Is there a need for mentoring for oral and maxillofacial surgery trainees?

PMID- 12180218
TI  - Angiocatheter as atraumatic fine suction tip for facial plastic surgery.

PMID- 12180219
TI  - First experience with a public domain computer-aided surgical system.
AB  - The outcome of complex craniofacial operations is critically dependent on careful
      and accurate preoperative planning. Recent advances in computer technology enable
      the surgeon to do surgical simulations directly on to a computer terminal. We
      describe the clinical application of a public domain-based computer-aided system
      in craniofacial surgery. Operation planning was based on clinical investigations
      and radiological images, with particular use of a virtual three-dimensional
      surgical simulation. Three patients with complex craniofacial malformations were
      admitted for orbital correction. Surgical simulation defined numerically the
      extent of bone movements and the extent of resection areas. Operations were
      guided by the virtual planning. The outcome was compared with the planning to
      assess the accuracy of the operative correction. Our first experience confirms
      that computer-assisted simulation is a reliable and useful tool that improves
      surgical planning and helps to evaluate the surgical outcome.

PMID- 12180220
TI  - Assessment of clinical reasoning competence in urology with the script
      concordance test: an exploratory study across two sites from different countries.
AB  - OBJECTIVES: The script concordance (SC) test is designed to measure the
      organisation of knowledge that allows interpretation of data in clinical
      reasoning. This study explores the use of this new written examination tool in
      urology. MATERIALS AND METHODS: An 80 items SC test was administered to
      participants from a French and a Canadian university. Three levels of experience
      were tested: urologists (n = 22), residents in urology (n = 25) and students (n =
      23). Scores between groups were compared by analysis of variance. Reliability
      analysis was studied with Cronbach alpha coefficient. RESULTS: Mean global scores
      were 51.45 +/- 5.29 for students, 58.19 +/- 3.81 for residents and 62.27 +/- 5.46
      for urologists. The difference between the three groups was statistically
      significant (P < 0.00001). Interaction between levels of expertise and sites was
      apparently not significant (P = 0.326). Cronbach alpha was 0.79 for the test.
      CONCLUSIONS: This study shows that the SC test is able to discriminate among
      participants according to their levels of clinical experience in urology. The
      results are similar in two different learning environments. The SC test appears
      as a simple and direct approach to testing organisation and use of knowledge in
      urology.

PMID- 12180221
TI  - Prevalence and physician awareness of symptoms of urinary bladder dysfunction.
AB  - PURPOSE: To determine awareness of bladder dysfunction and attitudes towards its
      management among office-based physicians. MATERIALS AND METHODS: A total of
      211,648 patients consulting office-based primary care physicians (PCPs),
      gynaecologists (OBGs) or urologists (UROs) for any reason were given a
      questionnaire of four questions related to symptoms of bladder dysfunction. The
      physicians were asked to discuss the answers with their patients and to choose
      from a list of suspected diagnoses. They were also asked whether medical therapy
      would be initiated and/or the patient referred to a specialist. RESULTS: Patients
      (57%) had a least one symptom of bladder dysfunction, with increased frequency
      being most common (41.9%), and symptoms of stress incontinence (30.6%), urgency
      (24.3%) and urge incontinence (20.2%) less frequent. However, patients with
      symptoms of overactive bladder (OAB), mixed incontinence or stress incontinence
      according to the questionnaire remained undiagnosed by their physician in 57.5,
      47.5 and 38.1% of cases, respectively. When a diagnosis was suspected by the
      physician, it often did not match what would be expected based on the
      questionnaire, and in half of all cases did not result in medical treatment.
      CONCLUSIONS: Bladder dysfunction is highly prevalent among patients consulting an
      office-based physician for any reason, but remains undiagnosed in many cases and
      untreated despite diagnosis in many others. Since various effective treatment
      options are available for bladder dysfunction, educational programs for patients
      and physicians appear necessary to improve the quality of diagnosis and treatment
      for this wide-spread condition.

PMID- 12180223
TI  - Prognostic value of a combination of IPSS, flow rate and residual urine volume
      compared to pressure-flow studies in the preoperative evaluation of symptomatic
      BPH.
AB  - OBJECTIVE: Evaluate the predictive value of a combination of IPSS, uroflowmetry
      and ultrasound determination of residual urine volume in the determination of
      bladder outflow obstruction (BOO) and in predicting treatment outcome. METHODS:
      Forty-five out of a group of 60 BPH symptomatic patients were included.
      Preoperative evaluation: urine culture, PSA, uroflowmetry with sonographic
      measurement of post-void residual urine, DRE, IPSS with quality of life questions
      and pressure-flow study. Selection criteria for surgery were IPSS > 16 and Qmax <
      10 ml/s. Transurethral resection of the prostate was performed in these patients;
      the control visit was performed at 3 months. Treatment success was defined as
      Qmax above 15 ml/s, residual urine of less than 100 ml, a 50% reduction in IPSS
      and absence of urinary retention. RESULTS: Urodynamic abnormalities were found in
      42 patients (93.3%): 19 had detrusor instability, 5 patients showed impaired
      contractility, 37 patients had proven BOO, and 8 patients were unobstructed or
      mildly obstructed. The overall success rate was 86% when measured by the IPSS.
      Its preoperative value was 16.9, and dropped significantly to 4 (P = 0.005). The
      score improved significantly after surgery only in the obstructed group compared
      to the non-obstructed group (P = 0.001), however preoperative IPSS did not
      correlate with objective treatment results. CONCLUSIONS: A high proportion of
      patients successfully operated (71.1%) had a combination of IPSS > 16 and Qmax <
      10 ml/s, although BOO could not be accurately predicted with non-invasive methods
      alone. Patients with no or mild infravesical obstruction had only minimal
      improvement of IPSS and uroflowmetry following surgery.

PMID- 12180222
TI  - Symptomatic benign prostate hyperplasia: impact on partners' quality of life.
AB  - OBJECTIVES: Symptomatic benign prostate hyperplasia (BPH), besides affecting
      patients' quality of life through lower urinary tract symptoms (LUTS), and
      related acute events, may affect their partners' quality of life as well. The
      present study was focused on exploring partner morbidity in cases of symptomatic
      BPH patients being evaluated for surgical treatment. METHODS: The study group was
      comprised of 50 couples where male partners suffered from symptomatic BPH and was
      referred for further evaluation and, possibly, surgical treatment. Male subjects
      were asked to fill out the IPSS form, while the female partners were, separately,
      asked to fill out another structured questionnaire about 7 items (sleep
      disturbance, social disruption, performance of essential tasks, psychological
      impact, sex life, fear of cancer, fear of surgery). Data were analyzed in
      relation to the severity of symptoms (IPSS), patient's and partner's age,
      couple's age difference, marriage duration, mode and place of living. RESULTS:
      Partners' morbidity due to their husband's condition was comprised of sleep
      disturbance (28%); disruption of social life (30%) positively related to IPSS and
      negatively to the symptom duration; inability to take care of essential tasks
      outside and inside their house (8%); psychological burden (66%) positively
      related to the wife's age, the couple's age difference and the marriage duration;
      inadequate sex life (48%); fear of prostate cancer (62%); and fear of surgery
      (82%). CONCLUSIONS: Partners of patients with symptomatic BPH experience
      significant morbidity because of their husband's condition. The severity of
      patients' symptoms, however, is not always related to partners' morbidity.
      Partners should be adequately informed of the benign nature of the disease, as
      well as, the possible operating risks.

PMID- 12180224
TI  - Comparison of local povidone-iodine antisepsis with parenteral antibacterial
      prophylaxis for prevention of infective complications of TURP: a prospective
      randomized controlled study.
AB  - OBJECTIVE: To determine whether antisepsis with povidone-iodine solution applied
      at the external urethral meatus confers protection against infective
      complications following transurethral resection of the prostate (TURP) and
      compare that with antibacterial prophylaxis. METHODS: A total of 167 patients
      with sterile urine undergoing TURP for benign prostatic hyperplasia (BPH) were
      prospectively randomized into three groups. Group A, had gauze soaked in saline
      applied at the urethral meatus (control group). In group B, the gauze was soaked
      in povidone-iodine instead of saline and group C had a single 1 g i.v. injection
      of cephradine at induction of anaesthesia with no treatment for the meatus.
      Bacteraemia, post-operative bacteriuria and other infective complications were
      compared in the three groups. Associations of bacteriuria at catheter removal and
      intra-operative bacteraemia with infective complications and with long term
      bacteriuria were also studied. RESULTS: Bacteriuria rate at catheter removal was
      not significantly different in the three groups. However, intraoperative
      bacteraemia and bacterial growth at the external urethral meatus was
      significantly lower in group C. Bacteriuria at catheter removal was significantly
      associated with bacterial growth at the meatus but not with long term bacteriuria
      at 3 months. Bacteriuria at catheter removal could not accurately predict
      infective complications. CONCLUSION: Post-TURP bacteriuria appears to be preceded
      by bacterial growth at the external urethral meatus. Antisepsis with povidone
      iodine solution application at the meatus does not confer adequate protection
      against meatal bacterial growth as that obtained by prophylactic antibacterials.
      Nonetheless, neither antibacterial prophylaxis nor local antisepsis could reduce
      bacteriuria rate in this study.

PMID- 12180225
TI  - Bone alkaline phosphatase serum level predicts the response to antiandrogen
      withdrawal.
AB  - OBJECTIVE: To analyze if the biochemical response to antiandrogen withdrawal
      correlates with total and percent free serum prostate specific antigen (PSA) and
      bone alkaline phosphatase (BAP). MATERIALS AND METHODS: A group of 46 patients in
      whom maximal androgen blockade (MAB) failed was included in this study. Flutamide
      was used in 32 patients and bicalutamide in 14. Total and free PSA and BAP were
      determined in serum the same day in which antiandrogen was withdrawn. Thereafter,
      serum PSA was determined every 15 days. A biochemical response was established
      when a decrease in serum PSA greater than 50% was observed. The duration of
      biochemical response was considered until the first of two consecutive PSA serum
      elevations. RESULTS: The rate of biochemical responses was 23.9%. The mean
      duration of responses was 5.2 months. The mean serum PSA in patients who
      responded to the antiandrogen withdrawal was 86.4 ng/ml, while it was 98.6 ng/ml
      in those who did not respond, P > 0.05. The mean of percent free PSA was 13.9 and
      17.7%, respectively, P > 0.05. However, the mean BAP in responder patients was
      significantly lower, 18.9 ng/ml versus 100.6 ng/ml, P < 0.03. The rate of
      responses to flutamide withdrawal was 25% and to bicalutamide withdrawal 21.4%, P
      > 0.05. Other factors as age, Gleason score, initial clinical stage and the
      period of antiandrogen exposure were also analyzed. However, none of them had
      statistical significance. Serum BAP was the only predictor of response in the
      logistic regression analysis and a cut-off point of 50 ng/ml provided a relative
      risk of 1.46 (95% CI 1.17-1.83). CONCLUSIONS: Lower serum levels of BAP seems to
      correlate with a better response to antiandrogen withdrawal. Moreover, a level of
      BAP higher than 50 ng/ml would predict strongly the absence of response.

PMID- 12180226
TI  - Multicentricity in renal cell carcinoma: can primary tumor location serve as a co
      determinant of surgical treatment?
AB  - OBJECTIVE: To assess the incidence of multicentricity in our series of renal cell
      carcinoma (RCC) patients and to investigate whether certain clinicopathological
      parameters could assist the selection of the appropriate surgical modality.
      METHODS: We performed a retrospective analysis of 235 RCC specimens that had been
      resected by radical nephrectomy at our institution from June 1995 to 2001.
      RESULTS: Twenty-six (11%) kidneys contained at least one small accompanying
      nodule. Fourteen (6%) kidneys exhibited satellite tumors that were histologically
      consistent with the adenomas, while "true" multicentricity was detected in 12
      (5%) specimens. In the latter, the number of concomitant foci was independent of
      the size of the primary tumor. No correlation was observed between histological
      pattern and multifocality. In five out of seven (71%) specimens that contained
      the main tumor mass within the upper or middle portion of the kidney, satellite
      lesions were found to be located at the mid-kidney, whereas specimens with lower
      pole RCC demonstrated no restriction in the distribution of accompanying nodules.
      All patients had been screened pre-operatively by ultrasonography and CT
      scanning. CONCLUSIONS: Our findings may be suggestive of a putative link between
      primary tumor location and multicentricity, although this relation could not be
      statistically confirmed. The 5% incidence of multicentricity renders the
      biological significance of satellite adenomas and/or adenocarcinomas unclear.

PMID- 12180227
TI  - Nephron-sparing surgery for renal angiomyolipoma.
AB  - INTRODUCTION: Renal angiomyolipoma (RAML) is a benign tumor composed of varying
      amounts of mature adipose tissue, smooth muscle and thick-walled blood vessels.
      RAML tend to grow over time requiring active intervention due to serious
      associated complications, such as hemorrhage and pain. Although RAML is an ideal
      tumor for organ preservation, data concerning efficacy of nephron-sparing surgery
      (NSS) are sparse. The aim of the study was to evaluate the efficacy of NSS in
      RAML with regard to renal function, tumor recurrence and surgical feasibility.
      PATIENTS AND METHODS: Charts of patients with pathologically confirmed RAML were
      reviewed and data recorded: tumor size, associated symptoms, intraoperative blood
      loss, serum creatinine, follow-up data with regard to tumor recurrence and long
      term renal function. A total of 28 patients were identified with RAML who
      underwent NSS because of tumor size > 4 cm, pain and/or to rule out malignancy
      due to radiographic features of uncertain interpretation. RESULTS: The median
      follow-up of all patients is 58 (3-114) months; median age was 55.6 (34-78)
      years, 24 patients were women, 4 patients were men. None of the patients
      developed a local recurrence. Median size of enucleated tumors was 5.5 (2.5-15)
      cm; indication for NSS was symptomatic tumor with hemorrhage in 4 patients (16%),
      prophylaxis of hemorrhage in 5 patients (20%) and radiographic features
      suspicious for malignancy in 16 patients (64%). In those cases, unenhanced and
      enhanced CT scans exhibit a hyperdense and a hypodense lesion as compared to the
      adjacent normal renal cortex, respectively. There were no intraoperative
      complications, median blood loss was 320 (50-1200) ml, none of the patients
      required blood transfusions. Post-operative course was uneventful in 26 patients
      (96%), 2 patients (7.1%) developed a urinary fistula managed by an endoluminal
      stent. Pre-operative serum creatinine was 0.9 (0.7-1.3) mg/dl, post-operative
      creatinine was 1.23 (0.7-1.5) mg/dl and serum creatinine at last follow-up was
      0.95 (0.7-1.2) mg/dl. CONCLUSIONS: NSS can be performed with a high success rate
      in RAML when surgical management is indicated. Long-term follow-up reveals no
      local tumor recurrences and stable renal function even in patients with a
      solitary kidney.

PMID- 12180228
TI  - Differential expression of bcl-2 family proteins in bladder carcinomas.
      Relationship with apoptotic rate and survival.
AB  - OBJECTIVE: To elucidate the role of various bcl-2 family molecules in the
      regulation of apoptosis and the progression of urothelial cancer, in relation to
      standard prognosticators. METHODS: Paraffin-embedded archival tissue from 103
      N0M0 consecutive patients with invasive bladder cancer (28 T1, 57 T2, 13 T3 and 5
      T4) was immunostained for bcl-2, bax, bcl-XL, bcl-Xs, p53, Ki-67 and with an anti
      single stranded DNA monoclonal antibody recognizing the apoptotic cells. Survival
      analysis was restricted to T2-T4 tumours. Patients were followed-up until death
      (n = 27) or for a mean (+/- S.D.) follow-up of 37.6 (+/- 17.4) months. Within
      this period, 39 patients relapsed after a mean (+/- S.D.) period of 13.6 (+/-
      12.3) months. RESULTS: Most tumours were immunoreactive for bax (73.1%) and bcl
      XL (80.9%) whereas bcl-2 and bcl-XS expression was comparatively less common
      (44.4 and 28.9%, respectively). The bcl-XL and bcl-XS positivity was related to
      high grade (P = 0.007) and advanced stage (P = 0.010), respectively. On the
      contrary, bax and bcl-2 positivity was unrelated to stage or grade. Apoptotic
      rate was independently influenced only by p53, bcl-2 and proliferation rate. In
      multivariate analysis of T2-T4 urothelial carcinomas (UC)s, only bax along with T
      category and age were the significant predictors of disease-free survival.
      Increased apoptosis and T-category were also independently related to the overall
      survival in T2-T4 UCs. CONCLUSIONS: The expression of bcl-2 family members
      appears to be differentially regulated in association with UC evolution. Most
      importantly, bax immunostaining offers additional information to that provided by
      traditional prognosticators, with regard to disease-free survival of T2-T4 UCs.

PMID- 12180229
TI  - Differences between local and review urinary cytology in diagnosis of bladder
      cancer. An interobserver multicenter analysis.
AB  - OBJECTIVES: The objective of the study is to evaluate the agreement of local and
      review urinary cytology in patients with newly diagnosed bladder cancer and in
      those being followed for their disease. In addition, the effect of the type of
      institution on agreement was determined. METHODS: A total of 652 consecutive
      patients with bladder cancer from 19 institutions were evaluated; 575 (88.2%) of
      the patients had cytopathological sample available for central review and were
      eligible for analysis. One hundred and twenty nine (22.4%) of the patients had
      newly diagnosed bladder cancer, whereas the remaining 446 (77.6%) patients were
      under follow-up. A voided urine sample was obtained prior to transurethral
      resection of the bladder (TURB) or routine follow-up cystoscopy and split for
      culture and cytology. The cytopathological samples were first analysed by a local
      pathologist, and then re-analysed by a central reviewer. The agreement of
      cytological readings was determined by Kappa coefficient. RESULTS: The
      sensitivities of local and review cytology in detection of primary bladder cancer
      were 38.8 and 31.0%, respectively. Recurrence was observed in 119 of the 446
      (26.7%) patients under follow-up, of which both local and review cytology
      detected 21 (17.6%) cases. Specificities of local and review cytology were 97.6
      and 96.6%, respectively. Overall agreement of urine cytology was good in patients
      with primary bladder cancer and moderate in those being followed for their
      disease as Kappa coefficients were 0.70 and 0.60, respectively. However, some
      disagreement was found when results were analysed according to type of
      institution, to type of primary tumour, and to result of follow-up cystoscopy. In
      patients with primary bladder cancer the Kappa coefficient was 0.86 (very good)
      in university hospitals and 0.36 (fair) in city hospitals. Accordingly, in
      patients under follow-up the Kappa coefficient was 0.65 (good) in university
      hospitals and 0.39 (fair) in district hospitals. Although the stage of primary
      tumour had no effect on agreement, agreement was moderate (Kappa coefficient
      0.45) in those with low grade tumour and good (Kappa coefficient 0.67) in those
      with high grade tumour. In addition, Kappa coefficients were 0.65 (good) and 0.40
      (fair) in those with and without recurrence at follow-up cystoscopy. CONCLUSIONS:
      Although overall agreement of routine cytology was from moderate to good in both
      diagnosis and monitoring of bladder cancer, there is some variation in agreement
      according to the type of institution. Accordingly, grade of primary tumour and
      the result of follow-up cystoscopy had effect on agreement reflecting
      subjectiveness and weak reproducibility of this test. This not only emphasises
      the need for continuing education and quality control for urine cytologic
      analysis, but also inspires the development of more objective tests.

PMID- 12180230
TI  - Accuracy of frozen section examination of testicular tumors of uncertain origin.
AB  - INTRODUCTION: A total of 80-90% of all testicular masses are malignant germ cell
      tumors. Benign testicular lesions are recognized in approximately 10-20% enabling
      a testis-preserving surgery on the findings of frozen section examination (FSE).
      However, there are only sparse information with regard to the reliability of FSE
      in testicular tumors of uncertain dignity. Therefore, we retrospectively reviewed
      our experience concerning the reliability of FSE in primary testicular tumors by
      comparing each FSE result to the final diagnosis. PATIENTS AND METHODS: From 1974
      to 2000, 354 patients were operated on a testicular tumor. During inguinal
      exploration and after clamping of the spermatic cord and appropriate dressing, a
      representative biopsy of the tumor was taken and sent for FSE. In case of
      malignancy radical orchiectomy was performed, in case of benign findings or in
      case of a germ cell tumor in a solitary testicle, the tumor was enucleated.
      Slides of FSE and the permanent sections were reviewed and compared with regard
      to the histological diagnosis and presence/absence of malignancy. RESULTS: Based
      on FSE, 317 tumors (89.5%) were found to be malignant ((100 seminomas (38.5%),
      217 nonseminomas (61.5%)) and 37 tumors (10.5%) were benign (17 epidermoid cysts,
      14 Leydig cell tumors, two cystadenomas, two simple cysts, two hemangiomas).
      Comparing FSE and definitive diagnosis, FSE correctly identified all malignant
      and benign lesions. There was a failure rate of 10 and 8% to differentiate
      seminomatous from nonseminomatous tumors and vice versa based on FSE, which,
      however, was irrelevant for the surgical management. Complications of the
      enucleations (n = 37) were: testicular atrophy in three cases, testicular
      hematoma in three cases, orchitis/epididymitis in one case. Not a single case
      disclosed a local relapse after a mean follow-up of 105 (12-240) months.
      CONCLUSIONS: Intraoperative FSE correctly identified all malignant and benign
      testicular masses including radical orchiectomy or organ-preserving surgery.
      Surgical management of testicular tumors based on FSE results is clinically
      practicable.

PMID- 12180231
TI  - Cigarette smoking as risk factor for erectile dysfunction: results from an
      Italian epidemiological study.
AB  - OBJECTIVES: We analysed the role of smoking on the risk of erectile dysfunction
      (ED) using data from a cross-sectional study on prevalence and risk factors for
      ED in the general population in Italy. METHODS: A total of 2010 men aged more
      than 18 years were randomly identified and interviewed by 143 general
      practitioners among their registered patients. Patients were asked "about their
      ability to achieve and maintain an erection sufficient for satisfactory sexual
      performance." If they were dissatisfied, they were defined as having ED. RESULTS:
      In comparison with never smokers, current smokers had an odds ratio (OR) of ED of
      1.7 (95% confidence interval (CI), 1.2-2.4) and ex-smokers of 1.6 (95% CI, 1.1
      2.3). The association between smoking and ED risk was present in subjects without
      a history of any cardiovascular disease, cardiopathy, hypertension, diabetes and
      neuropathy, but not in those with a history of these conditions. For example, the
      ORs of ED in smokers, in comparison with never smokers, were respectively 2.4,
      2.0 and 1.7 in men with no history of any cardiovascular disease, diabetes and
      neuropathy, but respectively 1.0, 1.0 and 1.2 in those with a history of the
      conditions. CONCLUSIONS: This study shows that the risk of ED is influenced by
      smoking and that the duration of the habit increases the risk. Further, it
      highlights the potential interaction of smoking with medical history on ED risk.

PMID- 12180232
TI  - Prevalence and correlates of erectile dysfunction in Turkey: a population-based
      study.
AB  - OBJECTIVES: Epidemiologic data indicate that erectile dysfunction (ED) is a
      significant problem among men worldwide. However, data do not exist for Turkish
      men. This study was conducted to determine the prevalence and sociodemographic,
      medical, and lifestyle correlates of ED in Turkey. METHODS: Information was
      gathered via physician-conducted interviews using a validated questionnaire.
      Respondents self-rated their ED as "none," "minimal," "moderate," or "severe".
      Bivariate and multivariate analyses were performed on data from a stratified
      random sample of 1982 men aged > or = 40 years to quantify the associations
      between ED and potential covariates. RESULTS: The age-adjusted overall prevalence
      of ED in Turkey was 69.2% (mild 33.2%, moderate 27.5%, severe 8.5%) and increased
      with age, as did severity of ED. When we consider moderate + severe ED cases, the
      prevalence is 36%. In a multivariate model, increased prevalence of moderate or
      severe ED was significantly associated with age, residence in eastern Turkey; low
      educational level; unemployment; or underlying diabetes, hypertension,
      depression, prostate problems or lower urinary tract symptoms. Conversely,
      residence in southern Turkey, alcohol consumption, physical activity, and higher
      income were significantly associated with decreased prevalence. CONCLUSIONS: ED
      affects a high proportion of Turkish men aged > or = 40 years, is correlated with
      a number of serious medical conditions and the frequency increases with age.

PMID- 12180233
TI  - The role of Acucise endopyelotomy in the treatment of ureteropelvic junction
      obstruction.
AB  - OBJECTIVE: Open surgical pyeloplasty has been the gold standard for the
      correction of ureteropelvic junction obstruction (UPJO). Endourological
      management of UPJO has gained increased acceptance, with reported success rates
      of 57-87%. It has been suggested that Acucise endopyelotomy (AE) should be the
      procedure of choice for patients with UPJO. The aim of this study was to assess
      the effectiveness of AE in the treatment of UPJO and the factors contributing to
      surgical outcome. MATERIALS AND METHODS: Forty-two patients (34 primary, 8
      secondary UPJO) underwent AE between June 1995 and December 1999. Presenting
      symptoms were; pain 34 (80.9%), UTI 10 (23.8%) and haematuria 5 (11.9%).
      Preoperative evaluation included ultrasound and/or intravenous urogram with
      diuretic renography. Hydronephrosis was graded in 36 patients. Of these 4, 14, 9
      and 9 had grade I, II, III and IV hydronephrosis, respectively. Twenty-four
      patients were stented prior to endopyelotomy and one required nephrostomy.
      Overall (true) success was defined as clinically pain free and radiologically no
      evidence of obstruction on diuretic scan. RESULTS: The average operating time was
      45 min and mean hospital stay was 2.7 days. Mean follow-up was 27 months (range 6
      55). The objective success rate was 52% and the subjective success rate was 64%.
      A total of 19 patients (45.2%) had long lasting clinical and radiographic
      treatment success. Three (7%) patients required nephrectomy and five (12%)
      underwent open pyeloplasty. Success rate for grade I/II hydronephrosis was 55.5%
      and only 27.7% with grade III/IV hydronephrosis. Normal renograms were found in
      12 (48%) of those with perioperative extravasation compared to three (25%)
      without. Only one of the eight patients with secondary UPJO had a normal post
      operative renogram. Size or type of stent used had no effect on surgical outcome.
      The substandard results were noted in patients with grade III/IV hydronephrosis,
      poor pre-operative renal function, secondary UPJO and without perioperative
      extravasation. CONCLUSIONS: Acucise endopyelotomy is a safe and minimally
      invasive procedure for the management of UPJO. Although the results of AE are
      suboptimal, its lower degree of invasiveness makes it reasonable choice for first
      line treatment. Careful selection of patients will improve the results of AE,
      although multicentre randomized trials are needed to make a valued comparison
      with other techniques.

PMID- 12180234
TI  - Flexible ureterorenoscopy for the treatment of lower pole calyx stones: influence
      of different lithotripsy probes and stone extraction tools on scope deflection
      and irrigation flow.
AB  - The 7.5 and 9.0 F flexible ureterorenoscopes are used widely in endourology.
      These scopes, along with new available tools and probes, enable intrarenal
      ureteroscopic access to renal stones in the lower pole. Following individual
      clinical experiences the infundibulopelvic angle has to be respected for the
      selection of different scopes, tools and probes. The aim of this study was to
      determine the influence of different scopes, tools and probes on the angle of the
      active and passive flexion of the flexible ureterorenoscope. The angles of the
      active and passive flexion and maximum irrigation flow of different flexible
      ureterorenoscope (9.0 F Wolf, 7.5 F Olympus, 7.5 F Storz) were measured
      repeatedly in vitro using nine different inserted tools and/or probes. In
      addition, the maximum allowing for easy passage of the nine different
      tools/probes through the channel of the scope were measured. The Olympus scope
      without working instrument present, allows for the greatest deflection. The
      flexible Lithoclast, the non-nitinol baskets, and the 365 microns laser probes
      significantly inhibit the deflection of all scopes. The greatest deflection with
      inserted working tool was possible using the Wolf and Storz scopes. Both nitinol
      tools as well as the 200 microns laser probe had only minimal influence on the
      deflection. The 200 microns laser probe reduces the irrigation flow from 50 to 28
      ml/min. In contrast, the baskets reduce the irrigation flow from 50 to 2 ml/min.
      There are significant differences of the active and passive flexion depending on
      the ureterorenoscopes itself and the different tools. In order to perform a
      successful flexible ureterorenoscopic stone treatment in the lower pole, the
      inhibition of the flexion of the different scopes together with the individual
      infundibulopelvic angle must be respected when selecting different tools and
      probes.

PMID- 12180236
TI  - Current role of simplified upper tract approach in the surgical treatment of
      ectopic ureteroceles: a single centre's experience.
AB  - OBJECTIVE: Despite renewed interest in either endoscopic decompression or
      complete reconstruction as primary approaches in ectopic ureterocele's (EU's)
      treatment, we advocate that a simplified upper tract approach is an optimal
      choice in a large subset of these patients. We review our surgical results to
      evaluate the effectiveness of different surgical procedures used in the treatment
      of EU, based on an individualized approach. PATIENTS AND METHODS: We
      retrospectively analysed all patients with EU and without previous treatment (n =
      59) operated in this centre between the years 1991 and 2000. This disorder was
      bilateral in three patients (62 EU) and associated with duplex ureters in 60
      cases. Vesicoureteral reflux (VUR) was diagnosed pre-operatively in 49.1% of
      patients. Treatment and choice of procedure was based on patients' age, clinical
      manifestations, associated abnormalities and function of the ureterocele-bearing
      moiety. Patients were divided in three separate groups according to the initial
      surgical approach. Group 1-11 patients submitted to endoscopic puncture (six
      urgent ureterocele decompression, four infants with obstruction of a functional
      ureterocele-bearing moiety and another with both lower pole ureter and mild
      bladder outflow obstruction). Group 2-30 patients (31 EU) submitted to a
      simplified upper tract approach--pyeloureterostomy (1), heminephrectomy (29) and
      nephrectomy (1) (all patients but one with non-viable renal segments; VUR, grade
      < or = III, present in six cases). Group 3-18 patients (20 EU) submitted to
      complete primary reconstruction (all patients with high-grade and/or
      contralateral reflux, with or without function of the ureterocele-bearing
      moiety). Success (clinically asymptomatic patients, without obstruction or VUR)
      and complication rates from the different approaches were analysed. For
      statistical evaluation, we used Fisher's exact test with p < or = 0.05 considered
      significant. RESULTS: The success rate of endoscopic treatment, simplified upper
      tract approach and complete reconstruction were 18.2%, 80% and 83.3%,
      respectively. Major complications occurred in two patients from group 3.
      CONCLUSION: Endoscopic puncture is our first option when immediate ureterocele
      decompression is required, although it seldom affords definitive treatment.
      Complete primary reconstruction is necessary in complex cases. Cure rates are
      high but there is a potential risk for serious complications. A simplified upper
      tract approach is curative in most patients without associated reflux.
      Heminephrectomy remains our first choice in a large subset of patients with non
      viable or hypofunctional renal segments and without high-grade reflux.

PMID- 12180235
TI  - Role of Oxalobacter formigenes in calcium oxalate stone disease: a study from
      North India.
AB  - OBJECTIVE: The present study was performed to detect the presence of an oxalate
      degrading bacteria Oxalobacter formigenes in the GI tract of calcium oxalate
      stone patients and normal individuals from North India. Furthermore, the possible
      relationship of this bacterium with number of stone episodes in this part of the
      world was also studied. The correlation of the presence or absence of O.
      formigenes with the urinary oxalate levels was evaluated. METHODS: DNA was
      extracted from the stool samples of 63 calcium oxalate stone formers and 40
      normal individuals. Polymerase chain reaction (PCR) was performed using genus
      specific primers for O. formigenes. The presence of which was confirmed by
      Southern blotting. Urinary oxalate levels were tested in each patient. RESULTS:
      As shown by PCR and Southern blotting, O. formigenes was present in 65% of normal
      individuals and in 30% of calcium oxalate stone formers. In patients with three
      or greater than three stone episodes colonies were present only in 5.6% of
      patients. Oxalate excretion was less in patients colonized with O. formigenes as
      compared to those with no colonization. CONCLUSION: In North Indian population
      the absence of O. formigenes can lead to a significant increase in the risk of
      absorptive hyperoxaluria and resultant recurrent calcium oxalate stone episodes.

PMID- 12180237
TI  - Chromosomal changes in incidental prostatic carcinomas detected by comparative
      genomic hybridization.
AB  - OBJECTIVES: The genetic changes underlying the development and progression of
      prostate cancer are poorly understood. To identify chromosomal regions in
      incidental prostatic carcinoma (T1a and T1b) was the primary aim of this study.
      MATERIALS AND METHODS: We used comparative genomic hybridization (CGH) to search
      for DNA sequence copy number changes on a series of 48 T1 prostate cancer
      diagnosed by transurethral resection (TURP) and by adenomectomy. Incidental
      prostatic carcinomas have not been studied by CGH previously. RESULTS: CGH
      analysis indicated that 14 cases (29.2%) of incidental prostatic carcinoma showed
      chromosome alterations. The most frequent alterations were chromosomal losses of
      8p (10.4%), 13q (6.3%), 5q (4.2%) and 18q (4.2%), and gains of 17p (10.4%), 17q
      (10.4%), 9q (6.3%) and 7q (4.2%). Minimal overlapping chromosomal regions of
      loss, indicative for the presence of tumor suppressor genes (TSGs), were mapped
      to 8p22 and 13q14.1-q21.3, and minimal overlapping regions of gain, indicative
      for the presence of oncogenes, were found at 9q34.2-qter, 17p12 and 17q24-qter.
      The statistical analysis displayed a significant association between chromosomal
      aberration detected by CGH and high Gleason score (P < 0.005) as well as between
      tumor categories T1a and T1b and chromosomal imbalance (P = 0.041). CONCLUSIONS:
      Studies directed at incidental prostatic carcinomas allow discovery of
      chromosomal changes in small and highly malignant tumors. Our results suggest
      that loss or gain of DNA in these regions are important in prostate cancer. This
      is the first study, which documents the spectrum of chromosomal changes in
      incidental prostatic carcinomas.

PMID- 12180238
TI  - CGA gene (coding for the alpha subunit of glycoprotein hormones) overexpression
      in ER alpha-positive prostate tumors.
AB  - OBJECTIVE: The precise role of estrogen, estrogen receptor (ER) and ER-responsive
      genes in prostate carcinogenesis is unclear. Paradoxically, estrogens and
      antiestrogens are used in the treatment of advanced metastatic prostate cancers.
      Recently, we identified CGA gene coding for the alpha subunit of glycoprotein
      hormones as a new ER alpha-responsive gene in human breast cancer cells. The aim
      of this study was to explore the role of CGA in the second major hormone-related
      cancer, i.e. prostate cancer. PATIENTS AND METHODS: We quantified CGA mRNA in
      nine cases of benign prostatic hyperplasia (BPH) and 23 sporadic prostate tumors
      (TP) by using a real-time quantitative reverse transcriptase-polymerase chain
      reaction (RT-PCR) assay. RESULTS: CGA overexpression (> 10 S.D. above the mean in
      normal prostate tissues (NP)) was observed in 39% of the TP (ranging from 4.4 to
      174.5 times the level in NP) and in none of the BPH samples. CGA overexpression
      was not accompanied by overexpression of the CGB, LHB, TSHB or FSHB genes to
      produce ectopic glycoprotein hormones. CGA gene overexpression correlated with ER
      alpha normal expression (P = 0.016), but not with ER beta or androgen receptor
      (AR) expression status. CONCLUSION: These results point to CGA gene as a member
      of a novel dysregulated pathway in prostate cancer. CGA should therefore be
      considered for investigation as possible novel molecular marker in clinical
      applications and as possible new potential therapeutic target.

PMID- 12180239
TI  - Prognostic significance of estrogen receptor expression in superficial
      transitional cell carcinoma of the urinary bladder.
AB  - OBJECTIVES: The role of estrogens in human bladder cancer still remains to be
      resolved. This study was undertaken to determine the estrogen receptor (ER)
      expression status and to elucidate the prognostic significance of ER in
      superficial transitional cell carcinoma (TCC) of the human bladder. METHODS:
      Tumor tissue blocks which were obtained by transurethral resection (TUR) from 121
      patients with superficial TCC and 30 control subjects were investigated. Median
      follow-up was 40 months. The expression of nuclear ER was evaluated by
      immunohistochemistry using avidin-biotin-peroxidase method and a monoclonal ER
      antibody. ER staining intensity in samples was assessed semi-quantitatively.
      Staining characteristics were compared with the clinico-pathological results.
      RESULTS: ERs were detected in 12.4% of the superficial TCC patients and in 10% of
      the controls (P = 0.73). No association was found between ER immuno-reactive
      score and patients' age, sex, tumor multiplicity or tumor size. An association
      between the ER staining intensity and higher tumor grade was observed (P = 0.01).
      Grades I, II and III tumors showed 10.6, 8.7 and 44.4% staining, respectively.
      Survival was not affected by ER expression. In multivariate analysis ER
      expression was not an independent prognostic factor. CONCLUSION: Superficial TCC
      of the bladder shows low ER expression and it appears that ERs do not have any
      direct role on the prognosis of patients with superficial TCC.

PMID- 12180241
TI  - Falls in cognitive impairment and dementia.
AB  - Older people with cognitive impairment and dementia are at increased risk for
      falls and subsequent adverse events. The most common risk factors for falls that
      are found specifically in patients with cognitive impairment and dementia are
      postural instability, medication, neurocardiovascular instability (particularly
      orthostatic hypotension), and environmental hazards. Based on data from studies
      in cognitively normal people who fall, modification of these risk factors may
      prevent falls in older people with cognitive impairment and dementia. Preliminary
      research in subjects with cognitive impairment and dementia suggests that
      physiotherapy may have a role in falls prevention. Additionally, risk-factor
      targeted interventions may reduce the risk of falls in patients who have
      cardiovascular abnormalities and neurocardiovascular instability.

PMID- 12180240
TI  - The epidemiology of falls and syncope.
AB  - Falls, syncope, and the associated complications are among the most serious
      problems that face the elderly population. The most common underlying causes and
      risk factors for falls include muscle weakness, gait and balance problems, visual
      impairment, cognitive impairment, depression, functional decline, and particular
      medications (especially in the presence of environmental hazards). Studies have
      identified the relative risks for these factors that enable a fairly accurate
      prediction of who is at high risk for falls and what areas to target for falls
      prevention activity. Causes and risk factors for syncope have not been studied as
      well in the older population. The most serious types of syncope have underlying
      cardiac etiologies but they cause less than 25% of the reported cases. The
      largest category of syncope (approximately 40%) is syncope of unknown etiology,
      which defies careful diagnostic evaluation but seems to be fairly benign. The
      epidemiology of these syndromes can provide extremely helpful insights for
      developing falls-prevention strategies.

PMID- 12180242
TI  - Intervention strategies and risk-factor modification for falls prevention. A
      review of recent intervention studies.
AB  - At least 21 randomized trials of falls-prevention interventions have been
      published in the past 10 years; thus, many falls clearly can be prevented. The
      most effective interventions are those that target community-dwelling people who
      are at high risk for falling. There is no doubt that for this group multifactor
      intervention is effective. Convincing evidence that exercise can prevent falls
      does exist, but the best type of exercise remains uncertain. Tai Chi, intensive
      strength and endurance training, and home-based exercises prescribed by a
      physiotherapist seem promising. Reducing the use of psychotropic medications does
      prevent falls, but the value of home modifications is still unclear.

PMID- 12180243
TI  - Neurally mediated syncope.
AB  - The prevalence and incidence of syncope increases with advancing years due to age
      related physiological changes in the neurocardiovascular, endocrine and renal
      systems. Cardiovascular syncope can present as falls because of amnesia for loss
      of consciousness or postural instability due to hypotension. Drop attacks or non
      accidental falls should thus be investigated for causes of syncope. The most
      common causes of neurally mediated syncope in older adults are carotid sinus
      syndrome, orthostatic hypotension and vasovagal syncope.

PMID- 12180244
TI  - Sick sinus syndrome.
AB  - Sinus-node dysfunction is common in the elderly and, in most cases, does not
      cause any symptoms. Despite the high number of laboratory investigations, most
      diagnoses of sinus-node dysfunction are made by 12-lead electrocardiography,
      which shows severe sinus bradycardia, sinus arrest, or sinoatrial block.
      Continuous electrocardiographic monitoring, exercise testing, and
      electrophysiologic investigations (including pharmacologic interventions to cause
      complete autonomic blockade) are sometimes useful in detecting transient or
      latent sinus-node abnormalities. The term sick sinus syndrome should be reserved
      for patients with symptomatic sinus-node dysfunction. Sick sinus syndrome has a
      protean presentation with variable degrees of clinical severity. Symptoms are
      often intermittent, changeable, and unpredictable. Because these symptoms can be
      observed in several other diseases, none are specific to sick sinus syndrome.
      Owing to the nonspecific nature of its symptoms, sick sinus syndrome can be
      diagnosed only when clear electrocardiographic signs corroborate symptoms. In the
      absence of a demonstrable link between signs and symptoms, a diagnosis can be
      presumed only when signs of severe sinus dysfunction are present and when every
      other possible cause of symptoms has been excluded carefully. Sinus-node
      dysfunction frequently is associated with diseases of the autonomic nervous
      system, and autonomic reflexes play a major role in the genesis of syncope.
      Survival does not seem to be affected by sick sinus syndrome. Atrioventricular
      block, chronic atrial fibrillation, and systemic embolism are major pathologic
      conditions that affect the outcome of the syndrome. Treatment should be aimed at
      controlling morbidity and relieving symptoms. Cardiac pacing is the most powerful
      therapy; physiologic pacing (atrial or dual-chamber) has been shown definitively
      to be superior to ventricular pacing.

PMID- 12180245
TI  - Atrioventricular block and problems with atrioventricular conduction.
AB  - This chapter has summarized briefly the current state of our knowledge on the
      incidence, etiology, presentation, investigation, and management of patients with
      AV block. The scope of the material covered has been widened intentionally to
      include a plethora of AV-conduction abnormalities because of the increases in the
      understanding of their clinical importance and contribution to left ventricular
      dysfunction. Under this heading, the critical importance of heart rate,
      maintenance of AV synchrony, and the sequence of ventricular activation and
      relaxation have been introduced and summarized briefly. The authors make a strong
      plea that, in the future, the reader consider AV-conduction abnormalities to be
      the parent topic, with the more-traditional, narrower subject of AV block forming
      a subunit thereof.

PMID- 12180246
TI  - Orthostatic hypotension.
AB  - A common problem among elderly people, orthostatic hypotension is associated with
      significant morbidity and mortality, which may be caused by medications, the
      cumulative effects of age- and hypertension-related alterations in blood pressure
      regulation, or age-associated diseases that impair autonomic function. Evaluation
      requires multiple blood pressure measurements taken at different times of the day
      and after meals or medications. Central and peripheral nervous system disorders
      should be sought, and the laboratory evaluation should concentrate on ruling out
      diabetes mellitus, amyloidosis, occult malignancy, and vitamin deficiencies. If
      orthostatic hypotension is detected, it should be considered a risk factor for
      adverse outcomes and treated first with nonpharmacologic interventions, including
      the withdrawal of potentially hypotensive medications. In patients with
      hypertension and orthostatic hypotension, the judicious treatment of hypertension
      may be helpful. For persistent, symptomatic orthostatic hypotension caused by
      autonomic failure, pharmacologic interventions include fludrocortisone,
      midodrine, and a variety of other agents. The careful evaluation and management
      of orthostatic hypotension will hopefully result in a significant reduction in
      falls, syncope, and fractures, and an attenuation of functional decline in
      elderly patients.

PMID- 12180247
TI  - Setting up a falls and syncope service for the elderly.
AB  - Establishing a neurocardiovascular investigation unit for the investigation of
      falls and syncope in the elderly is feasible. With the increasing growth in the
      elderly population, these units will be required to play an equally increasing
      role in both the clinical management of patients and the ongoing clinical
      research into the conditions that cause falls and blackouts in the elderly.

PMID- 12180248
TI  - Pacing interventions for falls and syncope in the elderly.
AB  - There is a high prevalence of cardiovascular disorders among elderly patients
      with recurrent falls or syncope, and cardiovascular causes are implicated in a
      significant proportion of three cases. Common cardiovascular causes of falls and
      syncope include carotid sinus syndrome, vasovagal episodes, sick sinus syndrome,
      and atrioventricular block. A comprehensive history and physical examination
      supplemented by electrocardiographic monitoring, carotid sinus massage, and tilt
      table testing in appropriately selected patients form the basis of the diagnostic
      evaluation to exclude a significant cardiovascular disorder. Patients with
      documented symptomatic bradycardia often benefit from pacemaker implantation, as
      evidenced by a reduction in recurrent events and improved quality of life.
      Although dual-chamber pacemakers, particularly those with rate responsiveness,
      provide more physiologic pacing than single-chamber ventricular devices, the
      superiority of dual-chamber pacemakers in reducing major clinical events has not
      been demonstrated. The efficacy of an aggressive evaluation and patient
      management strategy that includes pacemaker implantation for elderly patients
      with recurrent falls has been validated only by one prospective clinical trial;
      however, available data are compelling. For a variety of cardiovascular
      conditions, permanent pacemaker implantation has a demonstrated efficacy to
      prevent symptoms that arise from transient hypotension and decreased cerebral
      perfusion. The implication of these data is that many falls may be preventable
      through permanent pacemaker implantation in appropriately selected patients.

PMID- 12180249
TI  - Monitoring devices for falls and syncope.
AB  - Monitoring devices are an important adjunct to the clinical assessment of
      patients who experience falls. The use of these devices should be guided by the
      clinical history, a physical assessment, and routine investigations. Quantitative
      measures of postural sway should be used in conjunction with clinical measures to
      provide a more accurate assessment of gait and balance. Assessment of blood
      pressure changes during the investigation of neurocardiovascular causes of
      syncope and falls in older adults should be performed with noninvasive digital
      photoplethysmographic devices, so long as their appropriate use and limitations
      are applied and understood. Only minimal information can be gained from short
      term heart rate and rhythm monitoring in patients with infrequent symptoms. The
      usefulness of long-term ECG monitoring (with both external and implantable
      recorders) is well established for the diagnosis of unexplained syncope but
      requires further assessment in older individuals who experience falls. Twenty
      four-hour measurements of ambulatory blood pressure generally are not
      diagnostically helpful in patients who experience falls or syncope but do have a
      role in the monitoring of therapeutic interventions.

PMID- 12180250
TI  - Postprandial hypotension.
AB  - Postprandial hypotension is a prevalent condition in the elderly population and
      seems to be more common in frail elderly individuals who may be more susceptible
      to complications such as syncope and falls. Diagnosis is relatively easy and may
      be reversible in many cases. The epidemiology and pathophysiology of postprandial
      hypotension are not defined fully; however, a number of pathologic processes
      likely are involved, including abnormal sympathetic function, baroreceptor
      function, and vasoactive peptide release and activity. The precise relationship
      between symptoms and postprandial reductions in blood pressure is unclear. Blood
      pressure maintenance after a meal may depend on the interaction of some or all of
      the mechanisms outlined previously to compensate for the increase in bowel blood
      volume. The impairment of one or more of these mechanisms could result in
      inadequate compensation that leads to hypotension. If so, the presence of
      symptoms depends on that individual patient's ability to exercise adequate
      compensatory cerebral autoregulation. A hypertensive elderly patient may
      experience symptoms with only a small reduction in blood pressure, whereas a
      patient with autonomic failure may require a much larger fall in blood pressure
      to occur before they become symptomatic. The current definition of postprandial
      hypotension uses a threshold of 20 mm Hg as a cut off for diagnosis, but this may
      not be relevant to the presence or absence of symptoms. Further epidemiologic
      data are needed. Additionally, there is a lack of controlled trial evidence for
      the drugs that are used to treat this condition, and treatment often is carried
      out on a trial-and-error basis. Further research must be performed to identify
      the specific pathophysiology in certain patient groups, such as elderly
      hypertensive patients and those with autonomic failure, and to identify effective
      pharmacologic therapies that can be supported by randomized, placebo-controlled
      trials.

PMID- 12180252
TI  - When is intracardiac electrophysiologic evaluation indicated in the older or very
      elderly patient? Complications rates and data.
AB  - The use of invasive EPS and catheter ablation is well established for many
      cardiac rhythm disorders. Because of the high prevalence of arrhythmias, which
      often are tolerated poorly in the elderly, and the increased frequency of adverse
      effects of pharmacologic therapy in this population, the potential for benefit
      from invasive EPS and catheter ablation is great. The notion that elderly
      patients are at increased risk of complications from invasive EPS is not borne
      out by available data. Therefore, the suitability of this form of diagnostic and
      therapeutic approach should be based on the assessment of the individual patient
      and the clinical context, while taking into consideration patient-specific risks,
      goals, and expectations in adopting an invasive strategy.

PMID- 12180251
TI  - Atrial fibrillation and falls in the elderly.
AB  - Atrial fibrillation is an extremely rare cause of falls and syncope in the
      elderly. The routine use of ambulatory ECG monitoring to search for atrial
      fibrillation in elderly patients who fall is not recommended. Among elderly
      patients with atrial fibrillation who fall, short pauses of less than 3 seconds
      are nonspecific and are as common in patients who fall as they are in those who
      do not. Furthermore, most pauses are not associated with symptoms. Although the
      decision to implant a pacemaker for extremely long pauses is often
      straightforward, the decision to implant a pacemaker in patients who fall and who
      have short pauses ideally should be made after symptoms clearly have been
      associated with the dysrhythmia. This type of symptom-rhythm correlation is
      extremely valuable and often requires long-term ambulatory monitoring with
      external or internal (implanted) event or loop recorders. Among the growing
      population of elderly persons with chronic atrial fibrillation, oral
      anticoagulant therapy has been shown to have significant benefit and is
      underused, particularly in frail residents of long-term care facilities. The
      published literature does not support the commonly held belief that a patient's
      propensity to fall is an important factor in determining optimal antithrombotic
      therapy. Demographic shifts in the worldwide population continue to alter the
      practice of medicine, which is being influenced increasingly by the health care
      needs of the expanding elderly population. Additional research is needed to
      clarify the relationship between atrial fibrillation and falls in the elderly.

PMID- 12180253
TI  - Falls and syncope in elderly patients.

PMID- 12180254
TI  - [Quantitative cultures from catheters, using the Brun Buisson technique].
AB  - The objective of this collaborative work carried out in the Fundacion Favaloro
      and the Fundacion para la Lucha contra las Enfermedades Neurologicas de la
      Infancia, was to determine optimal conditions for incubation (time and
      atmosphere) of quantitative cultures of catheters processed according to the
      technique of vortex agitation (Brun Buisson method). From 689 processed
      catheters, 551 yielded negative cultures. From the 138 positive cultures, 125
      yielded monomicrobial cultures and 13 polimicrobial cultures (total number of
      microorganisms was 151). In the last situation each micoorganism was considered
      on an individual basis. A total of 58 episodes of catheter related bacteremias
      occurred, being 52 monomicrobial and 6 polimicrobial (total number of
      microorganisms was 64). When colony counts were compared in aerobic and in 5-10%
      CO2 atmospheres, a very good correlation was obtained (p = 0.27; r2 = 0.9268). No
      advantage was observed by incubating plates for more than 48 hours. Colony counts
      performed at the second versus the third day, and at the second day versus the
      seventh, gave very good correlation (p = 0.10 and r2 = 0.9996; p = 0.31 and r2 =
      0.9995, respectively).

PMID- 12180255
TI  - [Isolation of Plesiomonas shigelloides from a pediatric patient].
AB  - We report the isolation of P. shigelloides in the stools of a child with acute
      diarrhea living in the surroundings of Buenos Aires who usually drank untreated
      water. P. shigelloides has been implicated as an etiological agent in many
      sporadic cases of diarrhea, probably associated with drinking untreated water,
      eating uncooked seafood or foreign travel.

PMID- 12180256
TI  - [Absence of HTLV-I/II virus circulation in blood donors from the provinces of
      Santa Fe and Santiago del Estero].
AB  - In the present study, we evaluated the seroprevalence of HTLV-I/II infection
      among the blood donors in Santa Fe and Santiago del Estero provinces. A total of
      1327 serum samples from blood donors from Rafaela blood bank of Santa Fe province
      and 3382 serum samples from blood donors from Dr Edgar Bouzon blood bank of
      Santiago del Estero province were studied. The antibody screening was done by
      particle agglutination assay (PA) (SERODIA, Fujirebio Inc., Tokyo, Japan) or by
      enzyme immuno assay (EIA) (Abbott HTLV-I/HTLV-II EIA, Abbott, Germany). The "in
      house" indirect immunofluorescence assay (IFA) and Western blot (Bioblot HTLV
      Biokit, Barcelona, Spain) were used as confirmatory assays. All the samples
      resulted negative for specific antibodies against HTLV-I/II. These results
      suggest that HTLV-I/II are not circulating in low risk populations in these
      provinces or that the prevalences of infection would be lower than that reported
      by blood banks in other provinces of Argentina.

PMID- 12180257
TI  - [Group A bovine rotavirus: diagnosis and antigenic characterization of strains
      circulating in the Argentine Republic, 1994-1999].
AB  - Group A Bovine Rotavirus (BRV) has been identified as a major cause of neonatal
      diarrhea in cattle. The study was aimed to determine the prevalence of BRV and to
      antigenically characterize the G-types of circulating strains in dairy and beef
      herds in Argentina. A total of 1129 stool samples from diarrheic calves was
      analyzed from 1994 to 1999. The samples were initially screened for RV by ELISA
      and PAGE, and then G-typed using monoclonal antibodies (Mab) directed against G1,
      G2, G3, G6 and G10-specific epitopes. Forty percent (452/1129) of the samples
      were positive for RV by ELISA, while 24.7% (279/1129) were also positive for
      PAGE. VP7 was detected in the 70.5% (319/452) of the positive samples using a
      broadly reactive Mab (C60); 32.6% (104/319) were G6, 15.4% (49/319) were G10, and
      6% (19/319) were G1. However, 46.1% (147/319) of the samples remained untypable.
      Rotavirus diarrhea prevalences were comparable in beef and dairy herds (87.3% and
      a 74.4%, respectively). Finally, G6 was the most prevalent G-type circulating in
      beef herds while G10 prevailed in dairy herds. A better understanding of RV
      epidemiology will contribute to the optimization of current vaccines and
      prevention programs of RV diarrhea in calves.

PMID- 12180258
TI  - [Inhibition of the proteolytic activity of Helicobacter pylori by mouse immune
      serum].
AB  - The proteolytic activity (PA) of some microorganisms is an important pathogenic
      factor during tissue invasion. However, its role in Helicobacter pylori infection
      is not clear. Due to the importance of the immunological response to inhibit
      pathogenic factors of microorganisms, this study aims to establish an in vitro
      system to detect inhibitory antibodies to the PA of H. pylori in mouse serum. We
      obtained mouse sera from animals immunized by oral and intraperitoneal
      inoculations with the raw bacterial extract (BE) of H. pylori, in which we had
      previously detected PA. The degradation of azocasein subtract for BE was
      inhibited in 49.23% and 22.6% using 5 micrograms/ml of serum proteins (SP) from
      oral and intraperitoneal inoculation, respectively. However, when using more than
      25 micrograms/ml of SP of immune serum, PA was inhibited in a similar way than
      with control serum. In conclusion we present a methodology for the detection of
      inhibitory antibodies to PA of H. pylori in the serum of the immunized mouse.

PMID- 12180259
TI  - [Isolation and characterization of Shiga-toxin-producing Escherichia coli from
      frozen hamburgers and soft cheeses].
AB  - Shiga toxin producing-Escherichia coli (STEC), an important emerging foodborne
      pathogen, has been associated with bloody and non-bloody diarrhea, hemorrhagic
      colitis, hemolytic uremic syndrome (HUS) and thrombotic thrombocytopenic purpura.
      The cattle have been shown to be a major reservoir of STEC and raw foods such as
      ground beef and milk are the most common vehicles of infection. In the present
      study, the prevalence of STEC in 95 samples of frozen hamburgers and in 114
      samples of soft cheese was established in 8.4% and 0.9%, respectively. The
      genotypic and phenotypic characteristics of the strains were determined. The
      virulence genes stx1, stx2, eaeA and EHEC-hlyA were identified by PCR and by
      colony blot hybridization assays. Serotyping, antimicrobial susceptibility and
      production of Stx using specific cytotoxicity assays on Vero cells were also
      determined. All STEC strains were characterized as eaeA-/EHEC-hlyA+. The stx2
      genotype was prevalent (77.8%), and four different O:H serotypes were found,
      comprising: O8:H19 (5 strains), O113:H21 (1), O8:H16 (1), and O39:H49 (1). One
      STEC strain was nontypable. Although soft cheese complimented the microbiological
      quality controls for the coliform counts, the detection of STEC in one sample
      raises doubts concerning the effectiveness of the current quality controls. These
      data contribute to the implementation of strategies for the prevention and
      control of HUS.

PMID- 12180260
TI  - Use of a CO2 electrode to monitor fermentations that use xenobiotic compounds as
      source of carbon.
AB  - Bacterial strains were isolated from contaminated waters, mud or soils. They are
      capable of growing in mineral medium with different chemicals as carbon source,
      such as aliphatic or aromatic hydrocarbons and polychlorinated biphenyls (PCBs).
      Most of these strains tolerate high concentrations (up to 30% v/v) of the
      xenobiotic substrates. This is particularly important for the development of
      fermenting processes to treat effluents or residues with a high content of
      contaminating compounds. An ion-specific potentiometric electrode (CO2) has been
      developed to measure CO2 production continuously. When the different strains were
      incubated in a mineral medium and in the presence of the corresponding substrate,
      a parallel between growth, substrate consumption and CO2 production was found.
      The developed system is suggested as an efficient and economical alternative to
      evaluate the potential of biodegradation by different microorganisms.

PMID- 12180261
TI  - Salt stress response and proline accumulation in Brachiaria humidicola plants
      with and without mycorrhizal inoculation.
AB  - The work was carried out to investigate the effects of different concentrations
      of NaCl on Brachiaria humidicola Rendle in the presence and absence of Glomus
      etunicatum Becker and Gerdemann, as well as to evaluate some growth parameters
      and the accumulation of free proline in the plant leaves. The soil used was a
      Neosoil Fluvic Eutrophic with pH of 6.5, organic matter, 12.8 g kg-1 and soil
      texture, sandy loam, in which Brachiaria humidicola Rendle cv. 409 was grown.
      Five NaCl concentrations were tested 0; 0.22; 1.09; 1.96 and 2.84 g. kg-1 of
      soil, whose electrical conductivity (EC) were 2.22; 4.00; 8.13; 12.53 and 16.50
      dS m-1, respectively. Brachiaria humidicola showed salt tolerance when submitted
      to an EC of 4 dS m-1. There was a reduction of leaf area, dry matter of shoots
      and roots for the soil treatments beyond EC at 8 dS m-1. Free proline content in
      the leaves increased together with the increase in soil salinity (EC at 8 dS m-1)
      demonstrating that plants submitted to EC of 2 and 4 dS m-1 were less affected by
      salt stress, and consequently accumulated less proline in the leaves. Root
      colonization was not affected by the increase of NaCl dosage in the soil.

PMID- 12180264
TI  - Glyco-western blotting: biotinylated dermatan sulfate as a probe for the
      detection of dermatan sulfate binding proteins using western blotting.
AB  - Dermatan sulfate was biotinylated through the free amino residue of the core
      protein. The lysates of mouse and human lung culture cells were electrophoresed
      and blotted to a nitrocellulose membrane. The membrane was blocked successively
      with bovine serum albumin, avidin and biotin, and then treated with biotinylated
      dermatan sulfate followed by visualization using alkaline phosphatase conjugated
      avidin and its substrates. More than 30 bands were observed on the membrane when
      1 microgram/ml of biotinylated dermatan sulfate was used. The binding was
      prevented by an excess of dermatan sulfate but not chondroitin sulfate A or
      heparan sulfate. Some of the bands resisted washing with high salt concentration
      buffer. 60 kDa heat shock protein was found to be a dermatan sulfate binding
      protein upon two dimensional electrophoresis.

PMID- 12180263
TI  - Onychomycosis in Joao Pessoa City, Brazil.
AB  - Onychomycosis epidemiology is a combination of various factors which include,
      among others, clinical presentation, etiologic agents of the infection and the
      patient's history background. Out of a total of 672 nail samples examined, 460
      (68.4%) were microscopy positive for fungi and 306 (66.5%) of these were culture
      positive, including Candida (82%), dermatophytes (13.4%), Trichosporon spp (3.6%)
      and nondermatophyte molds (1%). Onychomycosis was more frequent in females
      (79.7%) than in males (20.3%). These were more common in fingernails (96.1%) than
      in toenails (60%) and yeasts were the most isolated etiologic agents. Among the
      clinical presentations, paronychia (CP) (57.2%) and onycholysis (CO) (24.8%) were
      the most common, caused frequently by C. albicans in 52.6% and 60.5% of the
      cases, respectively. T. rubrum (44.4%) and Trichosporon spp (22.2%) were the most
      frequent species in the case of distal lateral subungual onychomycosis (DLSO).
      Fusarium spp was the agent responsible for 33.3% of the cases of proximal
      subungual onychomycosis (PSO) and for 14.3% of white superficial onychomycosis
      (WSO), whereas Acremonium spp was responsible for 14.3% of the cases of WSO.

PMID- 12180262
TI  - Myeloperoxidase-generated phenothiazine cation radicals inactivate Trypanosoma
      cruzi dihydrolipoamide dehydrogenase.
AB  - Peroxidase/H2O2/phenothiazine systems irreversibly inhibit Trypanosoma cruzi
      dihydrolipoamide dehydrogenase (LADH). Inactivation of the parasite enzyme
      depended on (a) phenothiazine structure; (b) peroxidase nature; (c) incubation
      time and (d) the presence of a cation radical scavenger. With the
      myeloperoxidase/H2O2/system, promazine, trimeprazine, thioridazine,
      promethiazine, prochlorperazine, chlorpromazine and perphenazine were the most
      effective derivatives out of twelve phenothiazines studied. An electronegative
      substituent at position 2 of the phenothiazine ring such as Cl, or
      trifluoromethyl, propionyl and nitrile groups decreased or nullified
      phenothiazine activity. Myeloperoxidase/H2O2/, horseradish peroxidase/H2O2/, and
      myoglobin/H2O2/systems activated phenothiazines producing the corresponding
      cation radicals, myeloperoxidase being the most selective one with respect to
      phenothiazine structure. The myoglobin/H2O2/system activated phenothiazines that
      were scarcely active or inactivate with the MPO/H2O2/system, such as the
      trifluoromethyl derivatives. Production of phenothiazine cation radicals was
      demonstrated by optical spectroscopy. Phenothiazine cation radical stability
      depended on their structure as illustrated by promazine and thioridazine. Thiol
      compounds (GSH, N-acetyl-cysteine and penicillamine), aromatic aminoacids (L
      tyrosine, L-tryptophan, and the corresponding peptides) and ascorbate scavenged
      phenothiazine cation radicals, thus preventing LADH inactivation. Comparison of
      the summarized phenothiazine effects with those of phenothiazines on T. cruzi
      suggest the role of cation radicals in phenothiazines chemotherapeutic actions.

PMID- 12180265
TI  - Differential regulation of fibronectin fibrillogenesis by protein kinases A and
      C.
AB  - The assembly of fibronectin (Fn) matrix is a key event in regulating cell
      adhesion, migration and differentiation. To elucidate the regulatory role of
      protein kinases in the formation of fibrillar Fn matrix, we examined Fn fibril
      assembly from soluble bovine Fn underneath fibroblasts in Xenopus cell cultures
      and quantitated the resulting matrix by using a selectively cross-reactive
      antibody. The soluble form of bovine Fn was bath-applied to the cell cultures,
      and fibroblasts changed the soluble form of Fn into the fibrillar form in a time
      dependent manner. Integrin antagonists, Arg-Gly-Asp-Ser peptide and Rhodostomin,
      inhibited the formation of Fn matrix from soluble Fn. Genistein, cytochalasin D,
      colchicine, H-7, Ro-31-8220 and forskolin exerted similar inhibitory action.
      However, 12-O-tetradecanoyl-phorbol-13-acetate (TPA) significantly accelerated
      the formation of fibrillar Fn. The clustering of integrin and vinculin was
      enhanced and inhibited by TPA and forskolin, respectively. Following one day's
      incubation with soluble Fn to preorganize fibrillar Fn matrix, bath application
      of these drugs caused the degradation of the Fn network, indicating that Fn
      fibrillogenesis is a dynamic state modulated by cytoskeleton and protein kinases.
      Aprotinin and leupeptin selectively antagonized the Fn degradative action of
      forskolin, but not that caused by H-7. These results suggest that the dynamic
      assembly of Fn matrix is integrin- and cell-dependent and that both PKA and PKC
      play important roles in regulating the dynamics of Fn matrix. PKC activation
      enhanced the assembly of Fn, whereas inhibition of PKC caused the disassembly of
      Fn matrix. On the other hand, activation of PKA inhibited Fn assembly and caused
      the degradation of Fn matrix mainly via the activation of multiple proteolytic
      enzymes. Serine and cysteinyl proteases play important roles in Fn disassembly
      caused by PKA activation, but not that caused by PKC inhibition.

PMID- 12180266
TI  - Ontogeny of enhanced decorin levels and distribution within myocardium of failing
      hearts.
AB  - The proteoglycan, decorin, is a regulator of collagen fibril organization and its
      resulting functional properties. The temporal and spatial expression of decorin
      during the progression to heart failure is not well understood and may play a
      significant role in extracellular matrix remodeling. Decorin and types I and III
      collagen levels were measured in male Spontaneously Hypertensive Heart Failure
      (SHHF) and control Wistar-Furth rats at 2 and 8 mo, and at congestive heart
      failure (CHF). Decorin levels increased in the SHHF rats relative to the control
      rats in CHF. Type I collagen levels increased while type III levels decreased in
      the SHHF rats in CHF relative to the age matched controls. The SHHF rats have 48
      and 45 KDa isoforms of the decorin core protein expressed at all ages while
      control Wistar-Furths produced only a 45 KDa form. Decorin was localized in the
      outer ventricle wall but during CHF, decorin was expressed throughout the
      ventricular myocardium. Immunogold localization of decorin demonstrated an
      increased distribution of decorin along the myocardium collagen fibrils at CHF.
      The enhanced expression and greater distribution of decorin may be linked to
      extracellular matrix remodeling which occurs with the development of heart
      failure.

PMID- 12180267
TI  - Novel ultrastructural features as revealed by phthalocyanine reactions indicate
      cell priming for calcification in subdermally implanted aortic valves.
AB  - The roles played by various determinants in physiological, pathological or
      experimental calcification are still unclear. In this investigation, new insights
      were gained into structural changes occurring in porcine aortic valves undergoing
      mineralization in the rat subdermal model and then subjected to reactions with
      cationic phthalocyanines (PHTs), at salt-critical electrolyte concentrations
      (CEC). PHT reactions showed decalcifying effects, depending on both acidic pH in
      the media employed and mineral substitution by Cuprolinic Blue (CB) itself, as
      well as specific reactivity which enabled the ultrastructural detection of
      unusual, PHT-positive layers (PPLs) encircling cells and matrix vesicles, at 0.05
      M CEC conditions. Other reactions at different CEC conditions, or subsequent to
      enzymatical or specific extractive treatments, suggest PPL appearance is due to
      PHT uptake by clustered anionic phospholipids, which seem to be involved in
      mineral precipitation. PPLs present as a novel, reliable ultrastructural
      parameter indicating cell propensity in priming experimental and, possibly,
      pathological calcification.

PMID- 12180268
TI  - Alternative splicing of type II procollagen gene in the dedifferentiation of rat
      epiphyseal chondrocytes serially cultured in monolayer.
AB  - Type II procollagen is synthesized in two forms (IIA and IIB), generated by the
      alternative splicing of its precursor mRNA. The purpose of this study was to
      determine whether alternative splicing of type II procollagen pre-mRNA occurs
      during the dedifferentiation of chondrocytes in monolayer culture. We serially
      cultured rat epiphyseal chondrocytes for eight weeks in monolayer, and
      investigated the expression patterns of the two forms of type II procollagen
      transcripts according to the duration of the culture period. Reverse
      transcription-polymerase chain reaction and northern analysis revealed that both
      transcripts peaked on the day of cell isolation, but the expression level of IIB
      form was much higher than that of IIA form. The expression of IIA form decreased
      gradually, whereas the expression of IIB form decreased so rapidly that the ratio
      of type IIB and type IIA transcripts was reversed in the second week. In situ
      hybridization showed that all cells expressed type IIA mRNA throughout the
      culture period. The signal intensity for type IIA transcript decreased gradually
      in accordance with the results of RT-PCR and northern analysis. In situ
      hybridization of type IIB mRNA showed different results from in situ
      hybridization of type IIA mRNA. Like type IIA transcript, the freshly isolated
      chondrocytes and the cells in the first week showed positive signals for type IIB
      transcript. However, in the second week, positive signal was detected neither in
      polygonal cells nor large fibroblastic cells. Only a few cells of small size were
      weakly positive. From the third to the eighth week, no positive signal was
      detected. These findings indicate that alternative splicing of type II
      procollagen gene does occur and is regulated during the dedifferentiation of
      chondrocytes in monolayer culture.

PMID- 12180269
TI  - Identification of genes differentially expressed in cultured human osteoblasts
      versus human fibroblasts by DNA microarray analysis.
AB  - Little is known about patterns of gene expression from cells populating the
      connective tissues. This study investigated the possible variance of gene
      expression profile between human osteoblasts (HO) and human fibroblasts (HF) in
      vitro, using DNA microarray technology. Clustering identification was used to
      compare expression patterns between HO and HF for biological significance. Our
      results showed that genes encoding the extracellular matrix or apoptosis-related
      proteins tended to be expressed in greater abundance in HO, while more
      proteolysis-related proteins were expressed in higher level in HF. Significant
      differences in expression were also noted with genes related to signaling
      pathways. To confirm the array results, three genes (periostin, MFG-E8, MMP-10)
      were selected and analyzed independently by RT-PCR and northern blot. The results
      were found consistent with the array data in HO and HF. The present findings
      suggest that HO and HF differ not only phenotypically but in the expression level
      of tissue specific genes to assure the turnover and homeostasis of their
      respective tissues.

PMID- 12180270
TI  - Increased ash contents and estimation of dissolution from chemical changes due to
      in-vitro fluoride treatments.
AB  - The in-vitro fluoride treatment technique has been introduced to investigate the
      composite behavior of bone tissue. Bone tissue with different mechanical
      properties can be obtained by varying the concentration, pH and immersion time in
      fluoride ion solutions. The chemical and physical changes in intact pieces of
      bone treated in-vitro with different concentrations of fluoride ions are studied.
      The amount of bone mineral that does not contribute to the mechanical behavior of
      bone tissue is estimated from the dissolution occurring in the fluoride treated
      bones. Cortical bones from 18-month-old steers were treated in-vitro with 0.145,
      0.5 and 2.0 M sodium fluoride (NaF) solutions for three days. The dissolved bone
      mineral precipitates as calcium fluoride-like (CaF2/P with some phosphate [P]
      ions) and fluorapatite(FAp)/fluorhydroxyapatite(FHAp)-like materials within the
      bone tissue. The dissolution estimated from the presence of the precipitated
      fluoride phases is 5.6, 11.7, and 13.1% of the initial bone mineral content for
      the 0.145 M, 0.5 M, and 2.0 M NaF treatments respectively. Estimates of
      dissolution based on the measurements of phosphate and carbonate ions are lower
      and higher respectively when compared to the fluoride ion measurements. The wet
      and dry densities decreased slightly due to dissolution and re-precipitation
      while the ash content (ratio of the ash weight to dry weight) increased a small
      amount with increasing concentration of fluoride ion treatments. The increased
      ash content was due to the excess loss of water in the fluoride treated bones as
      compare to controls (untreated bone samples) during the drying process. The
      increased removal of water during the drying process may explain the increased
      ash contents in some in-vivo treatments.

PMID- 12180271
TI  - Regulation of tau phosphorylation and protection against beta-amyloid-induced
      neurodegeneration by lithium. Possible implications for Alzheimer's disease.
AB  - Alzheimer's disease is a neurodegenerative disorder characterized by the
      accumulation of the beta-amyloid peptide and the hyperphosphorylation of the tau
      protein, among other features. The most widely accepted hypothesis on the
      etiopathogenesis of this disease proposes that the aggregates of the beta-amyloid
      peptide are the main triggers of tau hyperphosphorylation and the subsequent
      degeneration of affected neurons. In support of this view, fibrillar aggregates
      of synthetic beta-amyloid peptide induce tau hyperphosphorylation and cell death
      in cultured neurons. We have previously reported that lithium inhibits tau
      hyperphosphorylation and also significantly protects cultured neurons from cell
      death triggered by beta-amyloid peptide. As lithium is a relatively specific
      inhibitor of glycogen synthase kinase-3 (in comparison with other protein
      kinases), and other studies also point to a relevant role of this enzyme, we
      favor the view that glycogen synthase kinase-3 is a crucial element in the
      pathogenesis of Alzheimer's disease. In our opinion, the possibility of using
      lithium, or other inhibitors of glycogen synthase kinase-3, in experimental
      trials aimed to ameliorate neurodegeneration in Alzheimer's disease should be
      considered.

PMID- 12180272
TI  - Modulation of synaptic plasticity by stress and antidepressants.
AB  - Recent preclinical and clinical studies have shown that mechanisms underlying
      neuronal plasticity and survival are involved in both the outcome of stressful
      experiences and the action of antidepressants. Whereas most antidepressants
      predominantly affect the brain levels of monoamine neurotransmitters, it is
      increasingly appreciated that they also modulate neurotransmission at synapses
      using the neurotransmitter glutamate (the most abundant in the brain). In the
      hippocampus, a main area of the limbic system involved in cognitive functions as
      well as attention and affect, specific molecules enriched at glutamatergic
      synapses mediate major changes in synaptic plasticity induced by stress paradigms
      or antidepressant treatments. We analyze here the modifications induced by stress
      or antidepressants in the strength of synaptic transmission in hippocampus, and
      the molecular modifications induced by antidepressants in two main mediators of
      synaptic plasticity: the N-methyl-D-aspartate (NMDA) receptor complex for
      glutamate and the Ca2+/calmodulin-dependent protein kinase II (CaM kinase II).
      Both stress and antidepressants induce alterations in long-term potentiation of
      hippocampal glutamatergic synapses, which may be partly accounted for by the
      influence of environmental or drug-induced stimulation of monoaminergic pathways
      projecting to the hippocampus. In the course of antidepressant treatments
      significant changes have been described in both the NMDA receptor and CaM kinase
      II, which may account for the physiological changes observed. A central role in
      these synaptic changes is exerted by brain-derived neurotrophic factor (BDNF),
      which modulates both synaptic plasticity and its molecular mediators, as well as
      inducing morphological synaptic changes. The role of these molecular effectors in
      synaptic plasticity is discussed in relation to the action of antidepressants and
      the search for new molecular targets of drug action in the therapy of mood
      disorders.

PMID- 12180273
TI  - Antidepressants and neuroplasticity.
AB  - OBJECTIVE: We review the literature on the cellular changes that underlie the
      structural impairments observed in brains of animals exposed to stress and in
      subjects with depressive disorders. We discuss the molecular, cellular and
      structural adaptations that underlie the therapeutic responses of different
      classes of antidepressants and contribute to the adaptive plasticity induced in
      the brain by these drugs. METHODS: We review results from various clinical and
      basic research studies. RESULTS: Studies demonstrate that chronic antidepressant
      treatment increases the rate of neurogenesis in the adult hippocampus. Studies
      also show that antidepressants up-regulate the cyclic adenosine monophosphate
      (cAMP) and the neurotrophin signaling pathways involved in plasticity and
      survival. In vitro and in vivo data provide direct evidence that the
      transcription factor, cAMP response element-binding protein (CREB) and the
      neurotrophin, brain derived-neurotrophic factor (BDNF) are key mediators of the
      therapeutic response to antidepressants. CONCLUSIONS: These results suggest that
      depression maybe associated with a disruption of mechanisms that govern cell
      survival and neural plasticity in the brain. Antidepressants could mediate their
      effects by increasing neurogenesis and modulating the signaling pathways involved
      in plasticity and survival.

PMID- 12180274
TI  - Different dependence of lithium and valproate on PI3K/PKB pathway.
AB  - OBJECTIVES: Acute treatment with valproate (VPA) or lithium (Li+) protects
      cerebellar granule cells (CGC) against apoptosis induced by low potassium (K+) (5
      mM). As the protection induced by VPA is absolutely dependent on insulin, in
      contrast to the observed effects of Li+, we decided to study the different role
      of the PI3K/PKB pathway in the neuroprotective effects of both drugs. METHODS: We
      have studied the neuroprotection elicited by Li+ or VPA in cultures of rat CGC.
      We induced the apoptosis by switching to a medium with a low concentration of K+
      or by adding C2-ceramide to the cultures. We studied the effect of Li+ and VPA on
      viability and on the regulation of the PI3K/PKB pathway. RESULTS AND CONCLUSIONS:
      Insulin also protects against low K(+)-induced apoptosis in CGC, probably through
      its interaction with an insulin-like growth factor receptor. Moreover, whereas
      Li+ protects against the apoptosis induced by C2-ceramide, VPA cannot, probably
      due to the inhibition of protein kinase B (PKB) caused in this apoptotic
      stimulus. These results suggest that VPA protects against low K(+)-induced
      apoptosis by acting on the PI3K/PKB pathway; however, VPA does not affect the
      increase of PKB activity caused by insulin in these cells. The protection by Li+
      is independent of this transduction pathway. Moreover, Li+ blocks the caspase 3
      activation induced by low K+, whereas neither VPA nor insulin affects this
      activation.

PMID- 12180275
TI  - Evaluation of neuroprotection by lithium and valproic acid against ouabain
      induced cell damage.
AB  - BACKGROUND: The pathophysiology of manic-depression may be associated with
      dysregulation of ion homeostasis. Ouabain is a potent inhibitor of the sodium
      potassium adenosine triphosphatase and has been purported to mimic abnormalities
      seen in acute mania. As manic episodes are believed to be neurotoxic and mood
      stabilizers have recently been implicated as neuroprotectants, it is of interest
      to determine if lithium and valproic acid antagonize ouabain-induced
      neurotoxicity. METHODS: Human neuroblastoma SH-SY5Y cells were differentiated for
      12 days then pretreated with lithium or valproic acid for 24 h and then
      challenged with a 10 microM ouabain insult. Cellular damage was assessed with
      lactate dehydrogenase (LDH) release, and apoptotic potential of ouabain was
      evaluated with DNA fragmentation. RESULTS: Ouabain significantly increased LDH
      release after 72 h of treatment. Lithium pretreatment at 1 mM diminished ouabain
      induced LDH release. Valproic acid alone at 100 and 1000 micrograms/mL
      significantly increased LDH release from the cells. Furthermore, it significantly
      potentiated ouabain-induced LDH release. DNA fragmentation suggests that ouabain
      induces apoptosis. CONCLUSIONS: Lithium at the therapeutic level of 1 mM limits
      the extent of cellular damage caused by 10 microM ouabain in SH-SY5Y cells as
      measured by LDH release. Valproic acid alone at the therapeutic concentration of
      100 micrograms/mL induces LDH release and does not prevent ouabain-induced LDH
      release.

PMID- 12180276
TI  - Topiramate versus bupropion SR when added to mood stabilizer therapy for the
      depressive phase of bipolar disorder: a preliminary single-blind study.
AB  - OBJECTIVE: Antiepileptic drugs (AEDs) are commonly employed in the treatment of
      bipolar disorder. The efficacy and tolerability of topiramate, a novel
      anticonvulsant, and bupropion SR when added to mood stabilizer therapy were
      compared under single-blind conditions (rater-blinded) in patients meeting DSM-IV
      criteria for bipolar I/II depression. METHODS: A total of 36 out-patients with
      Hamilton Depression Rating Scale (HDRS-17) scores > or = 16 were randomized to
      receive escalating doses of either topiramate (50-300 mg/day) or bupropion SR
      (100-400 mg/day) for 8 weeks. Data were analyzed on an intent-to-treat basis
      using the last observation carried forward method. RESULTS: The percentage of
      patients meeting a priori response criteria (> or = 50% decrease from baseline in
      mean HDRS-17 total score) was significant for both topiramate (56%) and bupropion
      SR (59%) [t(17) = 2.542, p = 0.04 and t(17) = 2.661, p = 0.03, respectively].
      Baseline demographic and clinical parameters were comparable between the two
      treatment groups. The mean doses of study medication were 176 mg/day (SD = 102
      mg/day) for the topiramate-treated group and 250 mg/day (SD = 133 mg/day) for the
      bupropion SR-treated group. A significant and comparable reduction in depressive
      symptoms was observed from baseline to endpoint following topiramate and
      bupropion SR treatment, according to a > or = 50% reduction in the HDRS-17. Total
      mean HDRS-17 scores significantly decreased from baseline to endpoint in both
      groups (p = 0.001), however, differences between the topiramate-treated group and
      the bupropion SR-treated group were not significant [t(36) = 1.754, p = 0.097].
      Both topiramate and bupropion SR were generally well tolerated. Thirteen patients
      discontinued the study: 2 because of lack of efficacy, 1 due to withdrawal of
      consent and 10 following side-effects (six in the topiramate and four in the
      bupropion SR-treated group). There were no cases of affective switch in either
      arm. Weight loss was experienced by patients in both groups (mean weight loss at
      endpoint was 1.2 kg in bupropion SR and 5.8 kg in topiramate) [t(17) = 2.325, p =
      0.061 and t(17) = 2.481, p = 0.043, respectively]. CONCLUSIONS: These preliminary
      data suggest that adjunctive topiramate may reduce depressive symptom severity in
      acute bipolar depression. The antidepressant efficacy of this compound requires
      confirmation via double-blind placebo controlled investigation.

PMID- 12180277
TI  - [Hepatitis C and alcohol].

PMID- 12180278
TI  - [Hepatitis C and drug use: epidemiology, screening, natural history and
      treatment].

PMID- 12180280
TI  - [Hepatitis C in France].

PMID- 12180279
TI  - [Chronic hepatitis C in HIV-HCV coinfected patients].

PMID- 12180282
TI  - [Natural history of HCV infection].

PMID- 12180281
TI  - [Modifications of epidemiological characteristics of hepatitis C].

PMID- 12180283
TI  - [Physiopathology of HCV infection].

PMID- 12180284
TI  - [Fibrosis in chronic hepatitis C infection: mechanisms and cofactors].

PMID- 12180285
TI  - [The role of liver biopsy in the management of chronic hepatitis C].

PMID- 12180286
TI  - [Management of patients with hepatitis C virus infection. Virological tests].

PMID- 12180287
TI  - [What are the indications for treatment of acute hepatitis C?].

PMID- 12180288
TI  - [Treatment of patients with chronic hepatitis C who have not been previously
      treated].

PMID- 12180289
TI  - [Treatment of patients with chronic hepatitis C virus infection and normal
      transaminases].

PMID- 12180290
TI  - [Treatment of chronic hepatitis C in children].

PMID- 12180291
TI  - [Treatment of extrahepatic manifestations associated with hepatitis C virus
      infection].

PMID- 12180292
TI  - [Treatment of hepatitis C virus-related cirrhosis].

PMID- 12180293
TI  - [Treatment of patients with chronic hepatitis C who relapsed or did not respond
      to a previous treatment].

PMID- 12180294
TI  - [Evaluation of response to treatment in chronic hepatitis C].

PMID- 12180295
TI  - [Treatment of hepatitis C after liver transplantation].

PMID- 12180296
TI  - [Treatment of chronic hepatitis C in special groups].

PMID- 12180298
TI  - [Treatment of hepatitis C in intravenous drug users].

PMID- 12180297
TI  - [Treatment of chronic hepatitis C and alcohol consumption].

PMID- 12180299
TI  - [Quality of life of patients with chronic hepatitis C: effect of treatments].

PMID- 12180302
TI  - [Chronic hepatitis C: apart from antiviral treatment what other measures should
      be recommended?].

PMID- 12180303
TI  - [What are the expectations of patients with chronic hepatitis C and how can they
      be satisfied?].

PMID- 12180301
TI  - [Treatment of chronic hepatitis C in patients coinfected with HIV: tolerability,
      drug interactions, therapeutic indications].

PMID- 12180300
TI  - [Treatment of chronic hepatitis C in patients with HIV coinfection: efficacy and
      tolerance].

PMID- 12180304
TI  - [Hepatitis C: therapeutic perspectives].

PMID- 12180305
TI  - Consensus conference. Treatment of hepatitis C.
AB  - This conference was organized according to the methodological rules published by
      the Agence Nationale d'Accreditation et d'Evaluation en Sante (ANAES). The
      conclusions and recommendations contained in this document were written, in full
      independence, by the jury of the conference. ANAES is in no way accountable for
      these views.

PMID- 12180306
TI  - [Treatment of acute hepatitis C].

PMID- 12180308
TI  - [Treatment of hepatitis C: advances and consensus].

PMID- 12180307
TI  - [Treatment of patients with chronic hepatitis C who never had been treated].

PMID- 12180310
TI  - [Treatment of chronic hepatitis C: side effects, tolerability and quality of
      life].

PMID- 12180309
TI  - [Chronic hepatitis C: what to do if the first treatment failed?].

PMID- 12180311
TI  - [Treatment of hepatitis C virus associated extrahepatic manifestations].

PMID- 12180312
TI  - [Hepatitis C and liver transplantation].

PMID- 12180313
TI  - [Natural history of hepatitis C virus infection].

PMID- 12180314
TI  - [Hepatitis C in certain patient populations: children, patients with hemophilia
      and thalassemia, the hemodialyzed and kidney transplant recipients].

PMID- 12180315
TI  - Effects of heavy resistance/power training on maximal strength, muscle
      morphology, and hormonal response patterns in 60-75-year-old men and women.
AB  - Eleven women (TRW; 64 +/- 4 yrs) and ten men (TRM; 65 +/- 5 yrs) participated in
      the strength/power training twice a week for 24 weeks. Basal concentrations of
      serum total and free testosterone, growth hormone (GH), dehydroepiandrosterone
      sulfate (DHEAS), cortisol and sex hormone binding globulin (SHBG) as well as
      acute responses of serum total and free testosterone, growth hormone (GH) were
      measured. Maximal 1RM strength in the squat, chair rise time and muscle fibre
      distribution and areas of type I and IIa and IIb of the vastus lateralis were
      also examined. 1RM squat increased in TRW by 26 (SD10)% (p < .001), and in TRM by
      35 (7)% (p < .001) and chair rise time improved in both groups (p < .001). Fibre
      areas increased in type I, (p < .01), IIa (p < .01) and IIb (p < .01) in TRM and
      type I (p < .05) and IIa (p < .05) in TRW. The proportion of type IIa increased
      from 31% to 43% (p < .05) in TRW and that of type IIb decreased from 27% to 17%
      (p < .05) in TRW and from 25% to 17% (p < .05) in TRM. Individual concentrations
      of testosterone/cortisol ratios correlated (r = 0.63; p < .05) with the
      individual increases in 1RM strength in TRW. The exercise sessions resulted in
      acute increases in serum GH in both groups (p < .05) with a further increase (p <
      .01) up to 10 minutes post-loading in TRM at post-training.

PMID- 12180317
TI  - Force-velocity relationship on a cycle ergometer and knee-extensor strength
      indices.
AB  - Maximal anaerobic power (Pmax) is often measured on a friction loaded cycle
      ergometer by means of an all-out exercise against a single braking force or from
      the force-velocity relationship. The relationship between braking force (F) and
      peak velocity (V) in cycling is linear: V = V0(1-F/F0) where V0 and F0 correspond
      to the intercepts with the velocity axis and force axis, respectively. The aim of
      the present paper was to test the hypothesis that parameter F0 expresses strength
      ability. The first study (12 male volleyball players) showed significant
      correlations between F0 and maximal isometric voluntary force (MVF) or maximal
      isometric rate of force development (MRFD) during isometric knee extension with
      data expressed either in absolute units (0.66 < r < 0.81, P < 0.01) or related to
      quadriceps muscle mass kgQ or kgQ2/3 (0.58 < r < 0.82, 0.05 < P < 0.001). In the
      second study (24 male athletes), F0 was significantly correlated with the peak
      torques in isokinetic Biodex knee extension at four angular velocities (0, 1.57,
      3.14 and 4.19 rad.s-1) with the values expressed in absolute units (0.49 < r <
      0.83, 0.05 < P < 0.001). When the results were related to kgQ or kgQ2/3 the
      correlation coefficients increased with velocity (0.22 < r < 0.69) and were
      significant (0.05 < P < 0.001) except at 0 rad.s-1. Nevertheless, the interest of
      the determination of F0 in addition to Pmax is questionable because similar
      coefficients of correlation were obtained between Pmax and strength performances.

PMID- 12180316
TI  - The lactate minimum test for cycling: estimation of the maximal lactate steady
      state.
AB  - This study evaluated the reliability and validity of the lactate minimum test
      (LMT), an incremental test given after lactic acidosis was induced by sprint
      exercise. This test is purported to accurately estimate the intensity of exercise
      at which the transport of lactate into and out of the blood is in equilibrium
      (maximal lactate steady state or MLSS) and should be a good predictor of
      endurance performance. Fourteen athletes (mean age 27.2 +/- 3.7 yrs) completed
      the following on Kreitler rollers: (a) two 20-km time-trials (35.1 +/- 3.3 and
      35.7 +/- 3.5 km.hr-1, p < .05); (b) two LMTs yielding lactate minimum speeds
      (LMS) of 33.6 +/- 3.4 and 33.4 +/- 3.1 km.hr-1 (p > 0.6); and (c) four constant
      intensity rides, at speeds bracketing the LMS. At 33.5 +/- 3.1 km.hr-1 plasma
      lactate concentration decreased 0.4 +/- 1.6 mM from 10 to 30 min. Plasma lactate
      increased 1.6 +/- 0.7 mM while riding 0.9 +/- 0.9 km.hr-1 faster. The LMT is a
      reliable (r2 = 0.904) and valid method to predict MLSS and a good predictor of
      endurance performance (LMT vs. 20-km time-trial, r2 = 0.86).

PMID- 12180318
TI  - Assuring gender equity in recruitment standards for police officers.
AB  - Human Rights Tribunals require application of non-discriminatory fitness
      standards in the hiring, promotion, and retention of employees. This issue has
      become controversial for public safety officers such as police, where differences
      in average levels of absolute fitness between men and women cause a high
      proportion of female applicants to fail many entrance tests. The present review
      summarizes the impact on physical working capacity of commonly encountered gender
      differences in size, body composition, haemoglobin levels, and muscular strength.
      The principles applied in designing content- and construct-validity occupational
      fitness tests are described, and Human Rights policies are reviewed in the light
      of the Meiorin judgment. Criteria are indicated for establishing a bona-fide
      occupational fitness requirement, and description is given of the approach used
      in developing standards that satisfy these criteria. Requirements are based on
      the task to be accomplished. The potential training response of female applicants
      is likely at least to match that of their male peers, and the needs of female
      police recruits are thus best accommodated by providing every opportunity to
      augment fitness to the required minimum level. The main weakness of any current
      requirement is that most police forces do not yet apply an equivalent criterion
      to older incumbent officers, where similar issues may arise.

PMID- 12180319
TI  - Modulation of force development by Na+, K+, Na+ K+ pump and KATP channel during
      muscular activity.
AB  - Extracellular K+ concentration increases during exercise and especially during
      fatigue development. It has been proposed that K+ is an important factor in the
      etiology of skeletal muscle fatigue because it suppresses membrane excitability
      and eventually force development. Based on the effect of K+, it has then been
      proposed the Na+ K+ pump reduces increases in extracellular K+ concentration
      while the ATP-sensitive K+ channel (KATP channel) allows for rapid increases in
      extracellular K+ to suppress force development when ATP levels start to fall or
      when the levels of metabolic end-products become high. However, recent studies
      have now demonstrated that an increase in extracellular K+ concentration can be
      advantageous to muscle during exercise because it not only stimulates
      vasodilation and the exercise pressor reflex, but it also potentiates force
      development when the Na+ concentration gradient is maintained. A new hypothesis
      is therefore proposed in which the Na+ K+ pump is important in maintaining the
      Na+ concentration gradient (and not the K+ concentration gradient as previously
      suggested), while the activation of KATP channels is important to increase the K+
      efflux and extracellular concentration. This situation then optimizes the
      development of force during exercise. Another hypothesis is proposed in which
      more KATP channels are activated while the activity of the Na+ K+ pump is reduced
      when ATP levels start to decrease to allow for an accumulation of intracellular
      Na+ and further increases in extracellular K+ concentration. These concentration
      changes then reduce membrane excitability and force development (i.e., fatigue)
      to protect muscle against large ATP depletion and function impairment.

PMID- 12180320
TI  - Chelation-assisted carbon-hydrogen and carbon-carbon bond activation by
      transition metal catalysts.
AB  - Herein we describe the chelation-assisted C-H and C-C bond activation of carbonyl
      compounds by Rh1 catalysts. Hydroacylation of olefins was accomplished by
      utilizing 2-amino-3-picoline as a chelation auxiliary. The same strategy was
      employed for the C-C bond activation of unstrained ketones. Allylamine 24 was
      devised as a synthon of formaldehyde. Hydroiminoacylation of alkynes with
      allylamine 24 was applied to the alkyne cleavage by the aid of cyclohexylamine.

PMID- 12180321
TI  - The separation of racemic crystals into enantiomers by chiral block copolymers.
AB  - A series of chiral double hydrophilic block copolymers (DHBCs) was synthesized
      and employed as additives in the crystallization of calcium tartrate tetrahydrate
      (CaT). We found that appropriate polymers can slow down the formation of the
      thermodynamically most stable racemic crystals as well as the formation of one of
      the pure enantiomeric crystals so that chiral separation by crystallization
      occurs even when racemic crystals can be formed. In addition, the presence of
      DHBCs results in major modifications of crystal morphology, creating unusual
      morphologies of higher complexity. Our study demonstrates the potential
      application of chiral DHBCs in the control of chirality throughout
      crystallization, in particular for racemic crystal systems, and also shows that
      enantiomeric excess of one enantiomer can be maximized by the kinetic control of
      crystallization.

PMID- 12180322
TI  - New scaffolds for supramolecular chemistry: upper-rim fully tethered 5
      methyleneureido-5'-methyl-2,2'-bipyridyl cyclodextrins.
AB  - Seven upper-rim fully tethered cyclodextrins (URFT-CDs) have been synthesised in
      a good average coupling yield using the one-step "phosphine imide" approach and
      their metal complexation behaviour with lanthanides and transition metals was
      explored. We observed that the A-TE-E light conversion process (antennae effect)
      occurs in the URFT-CD lanthanide complexes. A molecular redox switch based on the
      corresponding iron complexes is also reported. A reversible intramolecular
      translocation of the FeII and FeIII ions, between two distinct binding cavities
      has been monitored spectroscopically and achieved by chemical triggering.
      Finally, a negative allosteric control of ion recognition through the formation
      of a CD pseudocryptand is discussed.

PMID- 12180323
TI  - Thermal-, pressure-, and light-induced spin transition in novel cyanide-bridged
      FeII-AgI bimetallic compounds with three-dimensional interpenetrating double
      structures (FeIILx[Ag(CN)2]2).G.
AB  - Low-spin, high-spin and spin-transition behaviours have been observed for the
      doubly interpenetrating three-dimensional bimetallic compounds
      (FeII(pz)[Ag(CN)2]2).pz (pz = pyrazine), (FeII(4,4'-bipy)2[Ag(CN)2]2) (4,4'-bipy
      = 4,4'-bipyridine), and (FeII(bpe)2[Ag(CN)2]2) (bpe = bispyridylethylene),
      respectively. The single crystals of the bpe derivative undergo a spin transition
      with a large hysteresis loop at about 95 K. After several warming and cooling
      cycles, the single crystals become a microcrystalline powder with 50% spin
      transition. Influence of pressure--as well as light-induced excited spin-state
      trapping (LIESST) on the thermal 50% spin transition of the microcrystalline
      sample has also been investigated. Thermal spin-transition behaviour has also
      been induced at pressures higher than 1 bar for the 4,4'-bipy derivative. Both
      the 4,4'-bipy and bpe derivatives show strong pressure dependence of the spin
      state at 300 K.

PMID- 12180324
TI  - Synthesis and molecular tumbling properties of sialyl Lewis X and derived
      neoglycolipids.
AB  - The sialyl Lewis X (sLeX) epitope has become a prominent target for biological
      studies because of its role in inflammation through binding to selectins. This
      epitope is located at the terminal end in glycosphingolipids and a lactose unit
      serves as spacer to the ceramide moiety. This paper focuses on the influence of
      the spacer structure and spacer length in regard to the mobility of the sLeX
      epitope. To this end sLex neoglycolipids 1a-c, with one, two, or three lactose
      units as spacer between the sLeX tetrasaccharide epitope and the membrane anchor,
      were synthesized. The synthetic strategy was also applied to the synthesis of the
      corresponding Lewis X (LeX) derivatives. The glycolipids were inserted in model
      membranes, and the tumbling frequencies of the sLex tetrasaccharide epitopes were
      then analysed by NMR spectroscopy. A nonaethylene glycol spacer decouples the
      carbohydrate moiety from the membrane mobility while (oligo-)lactoses act as more
      rigid distance keepers between the Lewis epitope and the surface of the membrane.
      Quantification of the different degrees of decoupling was possible by analysis of
      rotational correlation times.

PMID- 12180325
TI  - Enantioselective Norrish-Yang cyclization reactions of N-(omega-oxo-omega
      phenylalkyl)-substituted imidazolidinones in solution and in the solid state.
AB  - The four N-(omega-oxo-omega-phenyl-alkyl)-substituted imidazolidinones 5-8 were
      prepared from N-acetylimidazolidinone (4). Upon irradiation, these substrates
      underwent Norrish-Yang cyclization to the racemic products rac-9-rac-12 (51-75%).
      The reactions of the N-2-oxoethylimidazolidinones 5 and 6 were conducted in
      tBuOH, and yielded 1:1 mixtures of exo/endo diastereoisomers rac-9a/rac-9b and
      rac-10a/rac-10b, accompanied by Norrish type II cleavage products. The reactions
      of the N-3-oxopropylimidazolidinones 7 and 8 were performed in toluene. The exo
      diastereoisomers rac-11a and rac-12a were the major diastereoisomers (d.r.
      approximately equal to 4:1). In the presence of the chiral compounds 1-3, the
      photocyclization of substrate 8 proceeded with significant enantiomeric excess (5
      60% ee). The more sophisticated complexing agents 3 and ent-3 provided better
      enantiofacial differentiation (up to 60% ee) than the lactams 1 and 2 (up to 26%
      ee). Low temperatures and an excess of the complexing agent helped to increase
      the enantioselectivity. The absolute configuration of the major exo product 12a
      obtained from compound 8 in the presence of complexing agent 3 was unambiguously
      established by single-crystal X-ray crystallography of its chiral N
      methoxyphenylacetyl derivative 15a. In a similar fashion, the absolute
      configurations of the endo products 12b and ent-12b were established. The N-2
      oxoethylimidazolidinone 5, which crystallized in a chiral space group, was
      irradiated in the solid state. At low levels of conversion, the product 9a/ent-9a
      was formed with high enantiomeric excess (78% ee). The enantioselectivity
      deteriorated at higher levels of conversion.

PMID- 12180326
TI  - Preparation and self-assembly of chiral porphyrin diads on the gold electrodes of
      quartz crystal microbalances: a novel potential approach to the development of
      enantioselective chemical sensors.
AB  - Porphyrin diad 1 was synthesized by reaction of the acyl chloride of porphyrin 2
      and trans-1,2-dithiane-4,5-diol. The Co complex of this diad was studied as a
      potential enantioselective receptor for chiral recognition in solution and in the
      solid state. In solution both enantiomers of limonene induce significant changes
      in the visible and circular dichroism (CD) spectra of [Co2(1)], while a different
      behavior is observed in the case of the enantiomeric pair of trans-1,2
      diaminocyclohexane. A different efficiency of [Co2(1)] chiral recognition is
      obtained for these compounds, with a remarkable degree of enantiodiscrimination
      observed in the case of limonene. Self-assembled monolayers of [Co2(1)] were
      deposited onto the gold electrodes of quartz crystal microbalances to be used as
      sensing materials of nanogravimetric sensors operating in the gas phase. The
      enantiodiscrimination properties of these sensors towards the enantiomeric pairs
      of chiral analytes have been studied. While in the case of analytes bearing donor
      ligand atoms we did not observe a remarkable enantioselectivity, a significant
      degree of chiral discrimination was observed in the case of limonene; this result
      is particularly encouraging for the potential development of enantioselective
      chemical sensors for use in an array configuration.

PMID- 12180327
TI  - Novel chiral pyromellitdiimide (1,2,4,5-benzenetetracarboxydiimide) dimers and
      trimers: exploring their structure, electronic transitions, and exciton coupling.
AB  - The chiral but highly symmetrical acyclic and cyclic pyromellitic diimide dimers
      and trimers 2-5 have been obtained and characterized for the first time. The
      pyromellitdiimide chromophores in these molecules are linked by a rigid
      diequatorially 1,2-disubstituted cyclohexane skeleton. The structures of the
      compounds have been determined in detail by molecular modeling and, in the case
      of cyclic dimer 4 and trimer 5, by means of X-ray diffraction analysis. The
      electronically excited states of the pyromellitdiimide chromophore (1a) have been
      studied in these and other model compounds by means of linear dichroism (LD),
      magnetic circular dichroism (MCD), and circular dichroism (CD) spectroscopy. CD
      spectra of the rigid cyclic trimer 5 have provided the most detailed information
      on the excited states of the pyromellitdiimide chromophore. The low-energy tail
      (340-360 nm) of the absorption envelope can be assigned to out-of-plane polarized
      n-pi* transitions (I, II). The higher energy bands are due to contributions from
      up to six pi-pi* transitions, these being polarized either along the long (IV-VI,
      VIII) or short axis (III, VII). The results of ab initio CIS/cc-pVDZ and
      semiempirical INDO/S-CI calculations have been compared with the experimental
      data. CD Cotton effects in the region 200-260 nm, which result from exciton
      interactions between electric dipole allowed transitions of two pyromellitdiimide
      chromophores in compounds 2-5, provide reliable and useful information concerning
      the conformation and absolute configuration of these molecules, which may be
      extrapolated to other oligoimide systems.

PMID- 12180328
TI  - Stereo- and enantioselective alkene epoxidations: a comparative study of D4- and
      D2-symmetric homochiral trans-dioxoruthenium(VI) porphyrins.
AB  - The mechanism of stoichiometric enantioselective alkene epoxidations by the D4-
      and D2-symmetric homochiral trans-dioxoruthenium(VI) porphyrins, [RuVI(D4
      Por*)O2] (1) and [RuVI(D2-Por*)O2] (2a), in the presence of pyrazole (Hpz) was
      studied by UV/Vis spectrophotometry and analysis of the organic products. The
      enantioselectivity of styrene oxidations is more susceptible to steric effects
      than to substituent electronic effects. Up to 72% ee was achieved for epoxidation
      of 3-substituted and cis-disubstituted styrenes by employing 1 as the oxidant,
      whereas entantioselectivities of only 20-40% were obtained in the reactions with
      2-substituted and trans-disubstituted styrenes. Complex 2a oxidized 2-substituted
      styrenes to their epoxides in up to 88% ee. Its reactions with trans-alkenes are
      more enantioselective (67% ee) than with the cis-alkenes (40% ee). Based on a two
      dimensional NOESY NMR study, 2a was found to adopt a more open conformation in
      benzene than in dichloromethane, which explains the observed solvent-dependent
      enantioselectivity of its reactions with alkenes. The oxidation of aromatic
      alkenes by the chiral dioxoruthenium(VI) porphyrins proceeds through the rate
      limiting formation of a benzylic radical intermediate; the observed
      enantioselectivity (eeobs) depends on both the facial selectivity of the first C
      O bond formation step and the diastereoselectivity of the subsequent epoxide ring
      closure. To account for the observed facial selection, "side-on" and "top-on"
      approach transition state models are examined (see: B. D. Brandes, E. N.
      Jacobsen, Tetrahedron Lett. 1995, 36, 5123).

PMID- 12180329
TI  - Theoretical clues to the mechanism of dioxygen formation at the oxygen-evolving
      complex of photosystem II.
AB  - The mechanism of the generation of dioxygen at the oxygen-evolving complex (OEC)
      of photosystem II (PSII), a crucial step in photosynthesis, is still under
      debate. The simplest unit present in the OEC that can produce O2 is a dinuclear
      oxo-bridge manganese complex within the tetranuclear Mn4 cluster. In this paper
      we report a theoretical study of the model complexes [Mn2(mu-O)2(NH3)6(H2O)2]n+
      (n = 2-5), for which density functional calculations have been carried out for
      several electronic configurations. The molecular orbital picture deduced from the
      calculations indicates that one-electron oxidation of the Mn2IV,IV/(O2-)2 complex
      (n = 4) mostly affects the oxygen atoms, thus ruling out the existence of a MnV
      oxidation state in this context, while the incipient formation of an O-O bond in
      the O2(3-) transient species evolves exothermally toward the dissociation of
      dioxygen and a Mn2II,III couple. These results identify the electronic features
      that could be needed to enable an intramolecular mechanism of oxygen-oxygen bond
      formation to exist at the OEC during photosynthesis.

PMID- 12180330
TI  - Pseudopeptide foldamers: the homo-oligomers of pyroglutamic acid.
AB  - As a part of a program evaluating substituted gamma-lactams as conformationally
      constrained building blocks of pseudopeptide foldamers, we synthesized the homo
      oligomers of L-pyroglutamic acid up to the tetramer level by solution methods.
      The preferred conformation of this pseudopeptide series in structure-supporting
      solvents was assessed by FT-IR absorption, 1H NMR and CD techniques. In addition,
      the crystal structure of the N alpha-protected dimer was established by X-ray
      diffraction. A high-level DFT computational modeling was performed based on the
      crystallographic parameters. In this analysis, we demonstrated that an alpha C
      H...O=C intramolecular hydrogen bond is responsible for the stabilization of the
      s-trans L-pGlu-L-pGlu conformation by 1.4 kcal mol-1. This effect can be easily
      detected by 1H NMR spectroscopy, owing to the anomalous chemical shifts of the
      alpha CH protons present in all of the oligomers. In summary, we have developed a
      new polyimide-based, foldameric structure that, if appropriately functionalized,
      has promise as a rigid scaffold for novel functions and applications.

PMID- 12180331
TI  - An unusual (10,3)-a racemic twofold interpenetrating network assembled from
      isolable tris(cyclopentadienyl)manganate and cesocene building blocks.
AB  - The syntheses and X-ray crystal structures of [([18]crown-6)2Cs](+)-[Cp3Mn]- (1),
      [([18]crown-6)2Cs](+)-[Cp'3Mn]- (2), [CsCp'] (3), [(CsCp')2-([18]crown-6)] (4),
      and Cs[MnCp3] (5), and the synthesis of Cs[MnCp'3] (6) are reported (Cp' =
      C5H4Me). The anions [Cp3Mn]- (1-) and [Cp'3Mn]- (2-) are characterized by eta 2
      coordination of all three Cp or Cp' rings. Measurements of the magnetic
      susceptibilities chi M resulted in values of mu eff = 6.20 microB (300 K), mu eff
      = 6.33 microB (301 K), and mu eff = 5.83 microB (300 K) for 1, 2, and 5,
      respectively, which are indicative of high-spin d5-Mn2+ centers. Density
      functional calculations illustrate that the coordination mode of 1- is
      characteristic for its sextet electronic ground state. Compound 3 forms infinite
      chains of cesocene-type sandwiches in the solid state, which are broken up into
      small subunits by the addition of crown ether to form 4. Compound 5 is a rare
      example of a (10,3)-a racemic interpenetrating network that crystallizes in the
      orthorhombic space group Pbca.

PMID- 12180332
TI  - Mechanism of the electrochemical conversion of aryl halides to arylzinc compounds
      by cobalt catalysis in DMF/pyridine.
AB  - The study of the electrochemical behavior of cobalt bromide, CoBr2, in the
      presence of zinc bromide, ZnBr2, and aryl halides, ArX, in a dimethylformamide
      (DMF)/pyridine (9:1, v/v) mixture allowed us to complete the study of the
      mechanism of the electrochemical conversion of aryl halides into arylzinc
      compounds by using cobalt catalysis. The last step of the catalytic process has
      been shown to be a transmetalation reaction between the arylcobalt(II) species
      and zinc ions that regenerates the cobalt(II) catalyst. The effect of zinc
      bromide on each step of the catalytic cycle has been studied. It is especially
      shown that the presence of ZnBr2 stabilizes the electrogenerated Co1 but has no
      effect on the rate constant of the oxidative addition of aryl halides, ArX, to
      Co1. Rate constants for the disproportionation reaction of Co1 and the oxidative
      addition have been determined in the presence of ZnBr2 and compared with the
      values obtained in its absence.

PMID- 12180333
TI  - Supramolecular architecture and magnetic properties of copper(II) and nickel(II)
      porphyrinogen-TCNQ electron-transfer salts.
AB  - The compounds [Cu(Tz)-(MeOH)2](TCNQ)2 (1), [Ni(Tz)-(MeOH)2](TCNQ)2 (2), [Cu(Tz)2]
      (TCNQ)7 (3) and [Ni(Tz)2](TCNQ)7 (4) (Tz = 2,7,12,17-tetramethyl-1,6,11,16
      tetraazaporphyrinogen) were obtained by metathesis reaction of [M(Tz)](ClO4)2
      with LiTCNQ and Et3NH(TCNQ)2, respectively. They were characterized by a
      combination of spectroscopic and physical methods. Compound 1 crystallizes in the
      monoclinic space group P2(1)/n with a = 8.310(2), b = 25.180(4), c = 20.727(4) A,
      beta = 93.58(2) degrees; Z = 4. Compound 3 crystallizes in the triclinic space
      group P1 with a = 11.244(1), b = 16.700(1), c = 17.321(1) A, a = 113.47(1), beta
      = 108.52(1), gamma = 96.12(1) degrees; Z = 2. The asymmetric unit of the compound
      1 is formed by cationic [Cu(Tz)(MeOH)2]2+ and by two crystallographically non
      equivalent TCNQ.- anions; these anions form dimeric units by overlap of the pi
      clouds. The dimers form hydrogen bonds with the metal-lomacrocyclic cation
      through the methanol ligands. According to this structure the compound is
      paramagnetic and behaves as an insulator in the temperature range studied. The
      paramagnetism arises only from the metal-complex moieties. Compound 3 shows an
      unprecedented structure due to the steric requirements of the macrocycle that
      favors the stacking of the TCNQ groups. The structure consists of infinite stacks
      of TCNQ units separated by the metal-macrocyclic units; there are seven TCNQ
      molecules per formula unit, one of which is formally mono-anionic, while the
      other six bear one half of an electron per molecule. The copper is six-coordinate
      in a very distorted octahedral environment. The Tz ligand is located in the
      equatorial plane and the apical nitrogens of the nitrile groups of two TCNQ
      molecules complete the coordination around the copper. The compound is a
      semiconductor and its magnetic behavior can be explained by the sum of the Curie
      contribution of the metal complex and the contribution arising from the magnetic
      exchange interactions of the spins located on the TCNQ units. The latter is found
      to be typical of one-dimensional antiferromagnetic distorted chains of S = 1/2
      spins and can be fitted according to a one-dimensional Heisenberg
      antiferromagnetic model.

PMID- 12180334
TI  - Setting the stage for new catalytic functions in designed proteins--exploring the
      imine pathway in the efficient decarboxylation of oxaloacetate by an Arg-Lys site
      in a four-helix bundle protein scaffold.
AB  - Fourteen 42-residue polypeptides have been designed to identify reactive sites
      for the catalysis of the decarboxylation of oxaloacetate, a chemical
      transformation that proceeds through the formation of an imine intermediate. The
      sequences fold into helix-loop-helix motifs and dimerize to four-helix bundles.
      The catalytically active lysine residues were incorporated in several surface
      exposed positions, but also in positions characterised by hydrophobic properties
      to reduce their pKa values. The molecular environments of the Lys residues were
      systematically varied, to find which residues were able to stabilise and bind the
      imine intermediate in the decarboxylation reaction. A two-residue Arg-Lys site
      formed the main component of the reactive site of the helix-loop-helix dimer
      Decarb-K34_R33, which obeyed saturation kinetics in catalysing the reaction with
      a kcat/KM of 0.59 M-1S-1. The rate constant measured was nearly three orders of
      magnitude larger than the second-order rate constant of the butylamine-catalysed
      reaction (0.0011 M-1S-1), and four orders of magnitude larger than the pseudo
      first-order rate constant of the uncatalyzed reaction (1.3 x 10(-5) s(-1)). The
      sequence of Decarb-K34_R33 contained only a single lysine residue. It was flanked
      by an arginine in the preceding position in the sequence. A flanking Arg residue
      provided more efficient catalysis than a flanking Lys or Gln residue. Arginines
      in flanking positions in the helix, in positions four residues before or after
      the Lys in the sequence, are not as important in catalysis as the Arg of the Arg
      Lys pair. The effect of pKa on the catalytic efficiency of the Lys residue in the
      decarboxylation reaction is well known. The identification of the role of the
      flanking Arg residue in catalysing decarboxylation, its optimal position, and the
      importance of conformational stability reported here sets the stage for
      developing a number of catalytic systems that depend on the formation of imine
      intermediates, but that lead to different reaction products.

PMID- 12180335
TI  - Control over calcium carbonate phase formation by dendrimer/surfactant templates.
AB  - Poly(propylene imine) dendrimers that are modified with long alkyl chains self
      assemble to form well-defined aggregates. The geometry and surface chemistry of
      the dendrimer assemblies can be varied through the addition of surfactants. These
      dendrimer/surfactant aggregates can be tuned to template the formation of the
      different phases of calcium carbonate. The use of octadecylamine results in the
      formation of polyhedral aggregates that become embedded within an amorphous
      calcium carbonate phase that persists in competition with the thermodynamic
      product, calcite. In combination with hexadecyltrimethylammonium bromide, small
      spherical aggregates are formed that induce the formation of vaterite. The use of
      the negatively charged surfactant SDS results in growth retardation by the Ca(2+)
      induced agglomeration of dendrimer/surfactant aggregates into giant spherical
      particles. Eventually these particles become overgrown by rhombohedral calcite.

PMID- 12180336
TI  - Experimental evidence for multiple oxidation pathways in the (salen) Mn-catalyzed
      epoxidation of alkenes.
AB  - The substrate electronic effects on the selectivity in the catalytic epoxidation
      of para-substituted cis stilbenes 2a-i were investigated by using (R,R)-[N,N'
      bis(3,5-di-tBu-salicylidene)-1,2-cyclohexanediamine]manganese(III) chloride 1 in
      benzene as the catalyst with iodosobenzene as the terminal oxidant. A Hammett
      study of the selectivity results reveals a stronger electrophilic character than
      previously assumed in the (salen)Mn-catalyzed reaction. In general, the best
      correlations with the experimental values were obtained by using the Hammett
      sigma + values, which gave rho = -1.37 for the rate of cis-epoxide formation and
      rho = -0.43 for the rate of the stepwise process leading to the corresponding
      trans product. The reaction involves two separate pathways as indicated also by
      the competitive breakdown of the intermediate on the path to trans epoxide for
      methoxy-substituted substrates. The asynchronicity in the concerted pathway
      leading to cis epoxide is apparent for 4-methoxy-4'-nitrostilbene, which yields
      cis epoxide with 75% ee entirely as a result of electronic effects.

PMID- 12180337
TI  - On the mechanism of arene-catalyzed lithiation: the role of arene dianions-
      naphthalene radical anion versus naphthalene dianion.
AB  - The use of lithium and a catalytic amount of an arene is a well-established
      methodology for the preparation of organolithium reagents that manifest greater
      reactivity than the classical lithium-arene solutions. In order to rationalize
      this conduct, the participation of a highly reduced species, the dianion, is
      proposed and its reactivity explored. Studies of kinetics and of distribution of
      products reveal that the electron-transfer (ET) reactivity profile of dilithium
      naphthalenide in its reaction with organic chlorides excludes alternative
      mechanisms of halogen-lithium exchange. The process generates organolithium
      compounds. The dianion thus emerges along with the radical anion as a suitable
      candidate for catalytic cycles in certain processes. Endowed with a higher redox
      potential than its radical anion counterpart, dilithium naphthalene displays a
      broader spectrum of reactivity and so increases the range of substrates suitable
      for lithiation. The reaction of dilithium naphthalene with THF is one example of
      the divergent reactivity of the radical anion and the dianion, which has been the
      source of apparent misinterpretation of results in the past and has now been
      appropriately addressed.

PMID- 12180338
TI  - Highly stereoselective and efficient synthesis of functionalized cyclohexanes
      with multiple stereocenters.
AB  - Chiral 7-oxo-2-enimides 2, which were readily obtained through a silyloxy-Cope
      rearrangement of syn-aldol products 1, have proved to be versatile substrates for
      a one-step, highly efficient and stereoselective synthesis of functionalized
      cyclohexanes. Organocopper and organoaluminum reagents have been employed as
      nucleophiles that underwent a conjugate addition to the enimide structure of the
      Cope products. The enolates formed in situ attacked the aldehyde or iminium ion
      in an intramolecular aldol or Mannich reaction, respectively, to directly yield
      cyclohexanols 3 and 4 and cyclohexylamines 5, respectively, in moderate to good
      yields and with excellent stereocontrol.

PMID- 12180339
TI  - Structure and chemistry of N-substituted corroles and their rhodium(I) and
      zinc(II) metal-ion complexes.
AB  - In the present work we report on the detailed structural features of the chiral
      N21- and N22-substituted benzyl and picolyl derivatives of
      tris(pentafluorophenyl)corrole [H3(tpfc)]. The main difference between the
      isomers is that substitution on N22 creates a much more crowded environment,
      reflected in higher deformation of the corrole ring from planarity and of the
      meso-aryls from perpendicular orientation. The effects of metal-ion chelation on
      corrole geometry are demonstrated by structural investigations of the zinc(II)
      and rhodium(I) complexes of the N21- and N22-alkylated corroles. The major
      finding is the intramolecular coordination of the pyridine moiety of the picolyl
      substituent in the case of [ZnII(N21-picolyl-tpfc)]. This pyridine is readily
      attracted to the zinc ion as an axial ligand, thus replacing the external
      pyridine molecule of the precursor [ZnII(N21-benzyl-tpfc)(py)]. The change is
      associated with a considerable flattening of the corrole ring in order to allow a
      more convenient coordination of the zinc ion to all four pyrrole nitrogen atoms
      (at Zn-N(pyr-role) distances of 1.956-1.987 A for the nonsubstituted sites, and
      2.224-2.247 A for the substituted sites). These structural investigations also
      aid a good understanding of the spectroscopic characteristics of the derivatives.

PMID- 12180340
TI  - Nanocrystalline metal oxides as destructive adsorbents for organophosphorus
      compounds at ambient temperatures.
AB  - Nanocrystals of magnesium oxide react with organophosphorus compounds at room
      temperature by dissociative chemisorption, which we term "destructive
      adsorption". This process involves cleavage of P-O and P-F bonds (but not P-C
      bonds) and immobilization of the resultant molecular fragments. These ultrafine
      powders have unusual crystalline shapes and possess high surface concentrations
      of reactive edge/corner and defect sites, and thereby display higher surface
      reactivity, normalized for surface area, than typical polycrystalline material.
      This high surface reactivity coupled with high surface area allows their use for
      effective decontamination of chemical warfare agents and related toxic
      substances. Herein data is presented for paraoxon, diisopropylfluorophosphate
      (DFP), and (CH3CH2O)2P(O)CH2-SC6H5 (DEPTMP). Solid-state NMR and IR spectroscopy
      indicate that all OR and F groups dissociate; this leaves bound -PO4, -F, and -OR
      groups for paraoxon, DFP, and DEPTMP, respectively. For paraoxon, it was shown
      that one monolayer reacts. For DEPTMP, the OR groups dissociate, but not the P
      CH2SC6H5 group. The nanocrystalline MgO reacts much faster and in higher capacity
      than typical activated carbon samples, which physisorb but do not destructively
      adsorb these phosphorous compounds.

PMID- 12180341
TI  - Stereoselective 1,2-cis glycosylation of 2-O-allyl protected thioglycosides.
AB  - The technique of intramolecular aglycon delivery (IAD), whereby a glycosyl
      acceptor is temporarily appended to a hydroxyl group of a glycosyl donor is an
      attractive method that can allow the synthesis of 1,2-cis glycosides in an
      entirely stereoselective fashion. 2-O-Allyl protected thioglycoside donors are
      excellent substrates for IAD, and may be glycosylated stereoselectively through a
      three-step reaction sequence. This sequence consists of quantitative yielding
      allyl bond isomerisation, to produce vinyl ethers that can then undergo N
      iodosuccinimide mediated tethering of the desired glycosyl acceptor, and
      subsequent intramolecular glycosylation, to yield either alpha-glucosides or beta
      mannosides accordingly. Although attempted one-pot tethering and glycosylation is
      hampered by competitive intermolecular reaction with excess glycosyl acceptor,
      this problem can be simply overcome by the use of excess glycosyl donor. Allyl
      mediated IAD is a widely applicable practical alternative to other IAD approaches
      for the synthesis of beta-mannosides, that is equally applicable for alpha-gluco
      linkages. It is advantageous in terms of both simplicity of application and
      yield, and in addition has no requirement for cyclic 4,6-protection of the
      glycosyl donor.

PMID- 12180342
TI  - Hexaphosphapentaprismane: a new gateway to organophosphorus cage compound
      chemistry.
AB  - Several independent synthetic routes are described leading to the formation of a
      novel unsaturated tetracyclic phosphorus carbon cage compound tBu4C4P6 (1), which
      undergoes a light-induced valence isomerization to produce the first
      hexaphosphapentaprismane cage tBu4C4P6 (2). A second unsaturated isomer tBu4C4P6
      (9) of 1 and the bis-[W(CO)5] complex 13 of 1 are stable towards similar
      isomerization reactions. Another starting material for the synthesis of the
      hexaphosphapentaprismane cage tBu4C4P6 (2) is the trimeric mercury complex
      [(tBu4C4P6)Hg]3 (11), which undergoes elimination of mercury to afford the title
      compound 2. Single-crystal X-ray structural determinations have been carried out
      on compounds 1, 2, 9, 11, and 13.

PMID- 12180343
TI  - Determination of transcription start site and analysis of promoter sequence,
      splice junction sites, intron sequence and codon usage bias of rat liver-specific
      organic anion transporter-1 (rlst-1/Oatp-4/Slc21a10) gene.

PMID- 12180344
TI  - Genetic mapping of the gene for SKI-1/S1P protease (locus symbol Mbtps1) to mouse
      chromosome 8.
AB  - Subtilisin/kexin isozyme-1 (SKI-1), otherwise known as Site-1 protease (S1P), is
      a Golgi proteinase mediating the proteolytic activation of the precursor to
      sterol-regulated element-binding proteins (SREBPs) 1 and 2, two transcriptional
      factors that regulate expression of a variety of genes involved in cholesterol
      and lipid metabolism. Using PCR and RFLP analysis on a panel of genomic DNA from
      a mouse intersubspecific back-cross, we have mapped the SK1-/S1P gene (locus
      symbol: Mbtps1) to the distal part of mouse chromosome 8, in a region that
      exhibits synteny homology to the human chromosome 16q24 region where its
      orthologue had been previously mapped.

PMID- 12180345
TI  - Characterization of a cDNA related to K-Cl Cotransporters in the root-knot
      nematode Meloidogyne incognita.
AB  - We report the cloning of a full-length cDNA from the plant-parasitic nematode
      Meloidogyne incognita, which encodes a putative protein of 1082 amino acids
      showing high similarity with K-Cl cotransporters (KCCs) from the free-living
      nematode Caenorhabditis elegans (54% identity) and from a number of mammals,
      including human. Hydropathy analysis indicates typical KCC topology patterns,
      with a hydrophylic NH2-terminal region, 12 membrane-spanning domains, and a long
      COOH-terminal hydrophylic region. Alignment of the nematode sequences with eleven
      KCC sequences from mammals suggests that the nematode proteins may constitute a
      separated family of KCCs. The M. incognita gene was shown to be expressed in both
      motile and sedentary stages, which suggests an important function in general
      physiology of the nematode. By analogy with known proteins, it is hypothesized
      that this gene is involved in the regulation of cell osmotic pressure to maintain
      nematode body fluids hyperosmotic to the environment.

PMID- 12180346
TI  - Complete mitochondrial DNA sequence and amino acid analysis of the cytochrome C
      oxidase subunit I (COI) from Aedes aegypti.
AB  - The complete sequence of the yellow fever mosquito, Aedes aegypti, mitochondrial
      cytochrome c oxidase subunit 1 gene has been identified. The nucleotide sequence
      codes for a 512 amino acid peptide. The AeCOI sequence is A + T rich (68.6%) and
      the codon usage is highly biased toward a preference for A- or T-ending triplets.
      The A. aegypti COI peptide shows high homology, up to 93% identity, with several
      other insect sequences and a phylogenetic analysis indicates that the A. aegypti
      sequence is closely related to two other mosquito species, Anopheles gambiae and
      A. quadrimaculatus. Comparisons of the nucleotide sequence for four A. aegypti
      laboratory strains revealed single nucleotide polymorphisms, with 25 nucleotide
      sites showing SNPs between strains. All SNPs occurred as synonymous transitions
      such that the peptide sequence is conserved among A. aegypti strains. RT-PCR
      analysis showed that COI is expressed at similar levels in all developmental
      stages and tissues.

PMID- 12180347
TI  - Nucleotide sequences of the internal transcribed spacers and 5.8S region of
      nuclear ribosomal DNA in Pinus taeda L. and Pinus echinata Mill.
AB  - The 615-bp nucleotide sequences of the first partial internal transcribed spacer
      (ITS-1), 5.8S rDNA and ITS-2 region from Pinus taeda L. (loblolly pine) and Pinus
      echinata Mill. (shortleaf pine) are reported. The two pine species show the same
      nucleotide sequences in this region, which indicates their close phylogenetic
      relationship. However, our reported nucleotide sequence in this region from
      shortleaf pine is different from the previous report for shortleaf pine in
      GenBank (accession number: AF037016). Our PCR-RFLP analysis of this region
      confirms our sequencing data. This correction is important for pine phylogenetic
      studies because it is located in the conserved 5.8S rDNA region.

PMID- 12180348
TI  - Contamination in the draft of the human genome masquerades as lateral gene
      transfer.

PMID- 12180349
TI  - Phylogenetic analysis of Hoxa 11 sequences reveals absence of transposable
      elements, conservation of transcription factor binding sites, and suggests
      antisense coding function.
AB  - Nine thousand and eighty-eight base pairs of the chicken Hoxa 11 gene, including
      8470 bases 5' of the translation start site were sequenced, and the
      characteristics of the upstream sequence investigated. Consistent with previous
      findings that middle repetitive elements are rare in the HoxA cluster, no
      repetitive elements were found other than simple oligonucleotide repeats.
      Multiple and pairwise alignments of the chicken upstream sequence with its human
      and mouse orthologs revealed multiple regions of 80% or higher homology across
      species. For the chicken, these regions were separated by sequences with no
      significant homology to human, mouse, or in most cases any other Genbank
      sequences. Selective clustering of transcription factor binding motifs was found
      to occur within the conserved homologous regions, suggesting evolutionary
      conservation of critical regulatory sequences. Of particular interest, seven
      conserved Cdx binding sites were found in the Hoxa 11 promoter, suggesting
      regulation by a non-clustered Caudal homeobox gene. Previous analysis of the
      mouse and human Hoxa 11 genes found a conserved antisense transcript, of unknown
      function. The chicken Hoxa 11 antisense strand included a conserved open reading
      frame capable of encoding 168 amino acids. Comparison of this region in mouse and
      chicken showed seven insertion/deletions, with each a multiple of three bases,
      thereby preserving open reading frame.

PMID- 12180350
TI  - Identification of the Xenopus laevis cDNA for EXT1: a phylogenetic perspective.
AB  - The EXT family of genes is involved in the developmentally important biosynthesis
      of heparan sulfate molecules. Members of the EXT family have a demonstrated role
      in gastrulation, wing formation in flies, and proper bone development in
      vertebrates. EXT family members have been isolated from several phylogenetically
      diverse species. We report here, the isolation of the first Xenopus laevis EXT1
      family member and discuss the evolutionary origins of this gene family.

PMID- 12180351
TI  - A novel two-component system of Bradyrhizobium japonicum: ElmS and ElmR are
      encoded in diverse orientations.
AB  - By completely sequencing the Bradyrhizobium japonicum insert of cosmid C27, a
      pair of genes was identified which was found to be highly similar to prokaryotic
      two-component systems. The genes of the putative regulator protein (214 aa),
      elmR, and the putative sensor histidine kinase (470 aa), elmS, are divergently
      oriented with their putative translational start sites separated by only 85
      nucleotides. This new locus is located about 10 kb upstream of the sipS signal
      peptidase allele. The highest similarities were found to regulatory proteins of
      methylotrophic bacteria. Genetically defined B. japonicum mutants were tested for
      their growth on different monocarbon compounds and for the symbiotic interactions
      with soybeans. Because no obvious phenotype could be observed the functional
      importance of this sensor/regulator-pair remains to be determined.

PMID- 12180352
TI  - Classification, epidemiology, risk factors, and natural history of peripheral
      arterial disease.
AB  - Peripheral arterial disease (PAD) is a clinical condition that has often been
      neglected. The clinical diagnosis of PAD may be made on the basis of an accurate
      history by using the WHO/Rose Questionnaire or the Edinburgh Questionnaire. From
      a clinical point of view, PAD may be classified into four stages. The PARTNERS
      Programme (PAD Awareness, Risk and Treatment: NEw Resources for Survival) is a
      recent study based on a partnership to improve PAD care. In this population, the
      prevalence of patients who were PAD+/CVD- was approximately 12% in males and 15%
      in females; PAD+/CVD+ approximately 18% in males and 14% in females; PAD-/CVD+
      28% in males and 17% in females; and finally, patients without vascular disease
      (PAD-/CVD-) 42% in males and 54% in females. The lessons derived from the
      PARTNERS Programme Study were informative; PAD is detectable in routine practice,
      using a simple, inexpensive, always available, clinical test such as calculation
      of the ankle-brachial pressure index (ABPI). Fewer than half of individuals with
      PAD are aware of their condition, while physicians are unaware of the presence of
      PAD in 70% of their patients with the condition. Diabetics and smokers are at
      high risk for PAD. Diabetes is present in about 41% of patients with PAD and a
      history of smoking (> 10 pack for year) is present in over 63% of patients with
      PAD. Antiplatelet therapy is taken by only about half of patients with PAD.
      Finally, the lack of diagnosis and treatment means that PAD patients remain at
      elevated risk of heart attack and stroke. Efforts must be made to diffuse this
      information to improve the diagnosis and treatment of PAD to reduce the risk of
      future fatal and nonfatal cardiac and cerebrovascular events.

PMID- 12180353
TI  - The pharmacology of cilostazol.
AB  - Cilostazol (6-[4-(1-cyclohexyl-1H-tetrazol-5-yl)butoxy]-3,4-dihydro-2(1H)
      quinolinone; OPC-13013) is a 2-oxo-quinoline derivative with antithrombotic,
      vasodilator, antimitogenic and cardiotonic properties. The compound is a potent
      inhibitor of phosphodiesterase (PDE) 3A, the isoform of PDE 3 in the
      cardiovascular system (IC50: 0.2 microM). In addition, there is inhibition of
      adenosine uptake, eventually resulting in changes in cAMP levels, dependent on
      the type of adenosine receptors (A1 or A2). Cilostazol inhibits platelet
      aggregation and has considerable antithrombotic effects in vivo. The compound
      relaxes vascular smooth muscle and inhibits mitogenesis and migration of vascular
      smooth muscle cells. In the heart, cilostazol causes positive inotropic and
      chronotropic effects. Most, if not all, of these actions are cAMP-mediated,
      including the modification of cAMP-controlled gene expression. Cilostazol
      decreases levels of serum triglycerides and causes some increase in HDL
      cholesterol levels. The compound has a number of additional effects which might
      contribute to its overall clinical efficacy. Cilostazol undergoes intensive and
      finally complete hepatic metabolism via the cytochrome P450 systems. This might
      result in some drug interaction, i.e. with erythromycin and omeprazole. The half
      life is approximately 10 h, resulting in about 2-fold accumulation of the drug
      during repeated administration.

PMID- 12180354
TI  - Evidence-based symptom relief of intermittent claudication: efficacy and safety
      of cilostazol.
AB  - Intermittent claudication (IC) is a common, debilitating symptom of
      atherosclerotic peripheral arterial disease. There are two therapeutic objectives
      in patients with IC: relief of symptoms and secondary prevention of acute
      thrombotic complications. Among patients with Fontaine stage II disease, surgical
      revascularization for symptom relief is reserved for those in whom
      exercise/lifestyle modification and medical therapy has failed. To improve
      exercise tolerance in IC requires favourable alteration in the oxygen
      supply/demand relationship in the lower limb. Following the largest ever clinical
      trials programme in patients with IC, cilostazol, a phosophodiesterase III
      inhibitor, has been licensed for symptom relief in the UK. In double-blind,
      randomized, placebo-controlled trials involving over 2000 patients, cilostazol
      100 mg b.d. produced significant and sustained improvements in pain-free and
      maximal walking distances as well as improved subjective assessments of quality
      of life. In particular, comparative studies with pentoxifylline (oxpentifylline)
      showed that cilostazol had significantly greater effects on functional outcome
      and exhibited good patient tolerance.

PMID- 12180355
TI  - Treating peripheral arterial disease in patients with diabetes.
AB  - Diabetes is associated with considerably higher risks of developing peripheral
      arterial disease (PAD) which, when it occurs, is more severe and progresses more
      rapidly than in nondiabetics. Early detection of PAD in the diabetic patient is
      therefore important, but may be complicated by the presence of neuropathy and
      calcification of the arteries such that ischaemic symptoms are not felt by the
      patient and ankle pressures are not reduced. Toe pressures are an alternative
      diagnostic tool in these patients. Good glycaemic control, while an essential
      part of diabetes management, does not appear to bring more than modest benefits
      in preventing the peripheral vascular complications of diabetes. Therefore,
      attention to other risk factors is needed. Treatment with the phosphodiesterase
      III inhibitor, cilostazol, has been shown to improve walking distances
      significantly in diabetes patients with intermittent claudication and also
      appears to improve plasma lipid profiles. Further, cilostazol has an antiplatelet
      action, which may prove to be of benefit in diabetes because hyperglycaemia is
      associated with increased platelet aggregability. Revascularization in diabetes
      patients with critical leg ischaemia is complex and associated with poorer
      outcomes than in non-diabetes patients. While surgical revascularization has
      better patency rates, in patients at high risk of surgical complications,
      percutaneous transluminal angioplasty may be a better option.

PMID- 12180356
TI  - Metabolic, endocrine and haemodynamic risk factors in the patient with peripheral
      arterial disease.
AB  - The morbidity and mortality associated with peripheral arterial disease (PAD)
      creates a huge burden in terms of costs both to the patient and to the health
      service. PAD is a deleterious and progressive condition that causes a marked
      increase in the risk of cardiovascular and cerebrovascular events. Further, PAD
      has a major negative impact on quality of life and mortality, and is associated
      with an increased risk of limb amputation. The clinical profile of patients at
      risk of PAD overlaps considerably with the known cardiovascular risk factors.
      These include, increasing age, smoking habit, diabetes, hypertension,
      dyslipidaemia, male sex and hyperhomocysteinaemia. For women, hormone replacement
      therapy appears to be associated with a reduced risk of PAD. Published PAD
      guidelines recommend aggressive management of risk factors, stressing the
      importance of lifestyle modification, antiplatelet agents, treating dyslipidaemia
      and diabetes. However, a large number of patients with PAD go undetected, either
      because they do not report their symptoms or because they are asymptomatic. It is
      therefore important to improve detection rates so that these patients can receive
      appropriate risk factor management.

PMID- 12180357
TI  - [Physical activity and life quality contribution in order to obtain a better
      healthy lifestyle].

PMID- 12180358
TI  - Beyond evidence-based medicine: bridge-building a medicine of meaning.
AB  - Contesting that a debate on evidence-based health care has taken place, this
      article charts three paths to the future: continuing avoidance of debate by
      proponents of evidence-based medicine (EBM); conflict, which the EBM movement
      courts and critics have espoused, and dialogue. The last portal allows for
      integration, which would end the disagreement between EBM and its critics and
      make a debate unnecessary. In search of integration, I sketch a bridge whose
      construction requires not compromise but a win- win approach. The bridge is a
      medicine of meaning (MOM). Consolidating multiple pillars of evidence to unify
      questions that are not necessarily the same for protagonists and critics of EBM,
      a MOM contends that the purpose or meaning of medicine is always healing and
      helping, and each party finds meaning in medicine by contributing to this common
      purpose in its own distinctive way.

PMID- 12180359
TI  - If not evidence, then what? Or does medicine really need a base?
AB  - This essay analyses the concept of ' base' in relation to its use in evidence
      based medicine (EBM). It evaluates the extent to which evidence provides a
      sufficient base for health care to rest and discusses whether medicine needs a
      base, and, if so, what are the other possible candidates. This paper will argue
      that EBM is linked epistemologically to the theory of foundationalism and shows
      how important criticisms of EBM emerge from anti-foundationalist epistemologies
      and interpretive frameworks. Drawing from recent writings in the philosophy of
      science, it is argued that there is a need to see multiple perspectives relevant
      to the practice and understanding of medicine.

PMID- 12180360
TI  - Reflexivity and metapositions: strategies for appraisal of clinical evidence.
AB  - According to Sackett, evidence-based medicine is the conscientious, explicit and
      judicious use of current best evidence in making decisions about the care of the
      individual patient. In this article, clinical reasoning is depicted as
      multilayered processes of evidence construction by means of social interaction
      and human interpretation. A basic set of knowledge is the doctors initial capital
      at the onset of the individual encounter. This is a necessary, but insufficient,
      presumption for the elaboration of clinical knowledge required to solve the
      particular problem. A diagnostic conclusion may appear to constitute the most
      obvious part of knowledge. Yet the formulation of hypotheses and the choice of
      adequate strategies for the pursuit of evidence are perhaps even more significant
      dimensions of clinical knowledge. Potential biases affect the ways in which
      evidence is gathered and used. When clinicians are not committed to appraising
      the evidence constituting the foundations of their enterprise, quality assessment
      of clinical practice becomes casual and unreliable. Reflexivity implies having a
      self-conscious account of the production of knowledge as it is being produced.
      From metapositions, critical questions can be asked and sometimes answered.
      Evidence-based practice in the original sense requires that doctors reflect upon
      their own positions as knowers, in the process of situated knowing, where certain
      rhetorical spaces rule.

PMID- 12180361
TI  - Data information and knowledge: the health informatics model and its role in
      evidence-based medicine.
AB  - The health informatics model consists of three essential parts: data, information
      and knowledge. These elements are arranged in a hierarchy, with data at the base
      of the model providing the basis for establishing information and leading in turn
      to the potential generation of knowledge. The informatics model converges closely
      with the principles, aims and tasks of evidence-based medicine (EBM),
      particularly as they relate to searching, appraising, reviewing and utilizing
      information and research. The development of health informatics today has its
      origins in the growth of statistics in the 18th and 19th centuries. As a new and
      growing discipline, statistics burgeoned amidst the challenge of measuring,
      monitoring and ultimately governing societies in the throes of massive change and
      expansion. The governance role embraced by statistics in the past resembles many
      aspects of the role ascribed to audit, quality assurance and EBM today. There are
      some deep-seated paradoxes within the field of health informatics. The
      informatics model posits an oversimplified and linear progression of data to
      information and knowledge. Health informatics may involve the spreading and
      dissemination of information but this should be seen as only a part, not the
      equivalent, of the complex process of generating knowledge.

PMID- 12180362
TI  - Clinical evaluation: constructing a new model for post-normal medicine.
AB  - The current paradigm in medicine is served by an explanatory model based on
      scientific positivism. We argue that there are inherent weaknesses in this model:
      its basis on reductionism, its reliance on linear thinking and its failure to
      incorporate human values invite a revision of our thinking about knowledge in
      medicine. We propose that a fresh explanatory model should be based on complexity
      theory, and argue that this better suits the new era of post-normal medicine,
      where analytical and predictive power are obtained by stepping back and looking
      at the relationships and overall context of a system rather than forcing reality
      into a preferred disciplinary framework. Better at times to be vaguely right, we
      argue, rather than precisely wrong.

PMID- 12180363
TI  - Impact of group structure and process on multidisciplinary evidence-based
      guideline development: an observational study.
AB  - RATIONALE, AIMS AND OBJECTIVES: This paper presents selected results from a study
      investigating the impact of small group processes on the development of clinical
      practice guidelines by multidisciplinary panels. Observations of one panel
      developing a guideline for primary care over several months are reported here.
      METHODS: Non-participant observation with content analy-sis of transcripts aided
      by field notes. RESULTS: Bales's interaction process analysis was used to
      categorize interactions in terms of their task-oriented or socioemotional
      qualities. This revealed a well-functioning, task-oriented group characterized by
      predominantly positive social behaviours. However, a breakdown of dialogue by
      speaker indicated a marked effect of professional role and status on the level of
      contribution to group discussions. This, and marked changes in panel composition
      across meetings, has implications for the multidisciplinarity of decision-making
      in such groups and hence for the acceptance and implementation of their outputs.
      CONCLUSIONS: These findings are likely to generalize to other health care
      settings in view of the growing emphasis on multidisciplinary decision-making and
      the clear status hierarchies inherent within the medical and allied fields.

PMID- 12180364
TI  - Physician knowledge, attitudes and practices regarding a widely implemented
      guideline.
AB  - RATIONALE, AIMS AND OBJECTIVES: Although clinical practice guidelines have been
      promoted widely, there is considerable concern that physicians have not
      incorporated them into their practice. Models suggest that a 'knowledge-attitude
      behaviour' sequence is important in modifying physician practice patterns. To
      address this, we examined physicians' knowledge of, attitudes towards and
      compliance with a widely implemented guideline - the Agency for Health Care
      Policy and Research (AHCPR) smoking cessation guideline. METHODS: A survey was
      mailed to a random sample of physicians at 128 veterans health administration
      facilities, which had implemented the guideline 2 years previously. RESULTS:
      Completed surveys were received from 879 physicians (50.3 response rate). Only 26
      of physicians reported receiving a copy or summary of the guideline, 44 reported
      little or no familiarity with it, 42 did not know if they agreed with it, 40 did
      not know if they complied with it and 46 did not know if it was effective.
      However, a high percentage of physicians reported that they always or usually
      explain the health risks of smoking (86) and that they always or usually suggest
      that their smoking patients stop (94). CONCLUSIONS: In spite of little
      familiarity with the guideline, the responding physicians reported practice
      patterns consistent with adherence to it. Knowledge is only one of a spectrum of
      barriers that affects physician adherence to guidelines. There are numerous
      opportunities for health care organizations to overcome the barriers to physician
      adoption of clinical practice guidelines in their day-to-day practice.

PMID- 12180365
TI  - Improving general practitioner records in France by a two-round medical audit.
AB  - RATIONALE, AIMS AND OBJECTIVES: The effectiveness of clinical audits in changing
      the practice of health care professionals is a moot point. Methods of
      implementation impinge directly upon outcomes. We investigated whether a network
      of local opinion leaders could contribute towards a successful audit. Our
      objectives were to: (i) bring about an improvement in record keeping in general
      practice; and (ii) increase GPs awareness of medical evaluation. METHODS: The GPs
      were recruited by local opinion leaders who had been briefed by the French
      National Agency for Accreditation and Evaluation in Health Care (ANAES, formerly
      ANDEM). On a given day (first round of the audit) they were invited to examine
      whether the medical records of their 10 first patients met 13 set criteria.
      Overall results were analysed by ANAES. Each GP was informed of how well they had
      fared compared with the regional and national averages and was provided with a
      standard set of recommendations. Anonymity was ensured by the local leaders. A
      second round was conducted 6 months later. RESULTS: A total of 244 GPs took part
      in both rounds of the audit; 32 dropped out after the first round. Their results
      were of a significantly lower standard. A significant improvement in results
      (P<0.025) was recorded between the two rounds for all 13 criteria of the
      questionnaire. Overall scores improved between the two rounds for 69 of the GPs
      and improved above average for 49. The greatest scatter in results was noted for
      items relating to medical history rather than to personal identity
      (administrative data). CONCLUSIONS: Self-assessment can help improve general
      standards of medical record keeping. A network of local opinion leaders, briefed
      by a national agency whose mission is to promote quality improvement in health
      care, seems to be an effective means of inducing participation in self
      assessment.

PMID- 12180366
TI  - The role of health informatics in clinical audit: part of the problem or key to
      the solution?
AB  - The concepts of quality assurance (for which clinical audit is an essential
      part), evaluation and clinical governance each depend on the ability to derive
      and record measurements that describe clinical performance. Rapid IT developments
      have raised many new possibilities for managing health care. They have allowed
      for easier collection and processing of data in greater quantities. These
      developments have encouraged the growth of quality assurance as a key feature of
      health care delivery. In the past most of the emphasis has been on hospital
      information systems designed predominantly for the administration of patients and
      the management of financial performance. Large, hi-tech information system
      capacity does not guarantee quality information. The task of producing
      information that can be confidently used to monitor the quality of clinical care
      requires attention to key aspects of the design and operation of the audit. The
      Myocardial Infarction National Audit Project (MINAP) utilizes an IT-based system
      to collect and process data on large numbers of patients and make them readily
      available to contributing hospitals. The project shows that IT systems that
      employ rigorous health informatics methodologies can do much to improve the
      monitoring and provision of health care.

PMID- 12180367
TI  - National sentinel clinical audit of evidence-based prescribing for older people:
      methodology and development.
AB  - RATIONALE, AIMS AND OBJECTIVES: This national clinical audit aimed to develop and
      implement a methodology to assess the appropriateness of prescribing for patients
      over the age of 65 in hospitals, general practice and nursing homes. METHODS:
      Organizations providing health care in the National Health Service in these three
      sectors were recruited into multi-disciplinary and inter-organizational local
      coalition teams. Prescription data and relevant clinical data were collected
      electronically on a customized database. The appropriateness of prescribing for
      specific conditions among the patients sampled was assessed by simple
      computerized algorithms, and users were provided with feedback to stimulate
      discussion and change. Use of the software tool was demonstrated to be feasible
      and its data reliable. Participants were re-audited, after a period of nationally
      guided and locally driven intervention, to evaluate levels of change. Local
      efforts to stimulate change and barriers to change were collected qualitatively.
      RESULTS AND CONCLUSIONS: The investigation revealed encouraging results and
      demonstrated the ability of audit to improve the quality of clinical services in
      given circumstances, although a multiplicity of questions relating to cost and
      methodology remain to be addressed.

PMID- 12180369
TI  - Reporting health care performance: learning from the past, prospects for the
      future.
AB  - In the USA, where public reporting of data on clinical performance is most
      advanced, comparative performance information, in the form of 'report cards',
      'provider profiles' and 'physician profiling', has been published for over a
      decade. Many other countries are now following a similar route and are seeking to
      develop comparative data on health care performance. Notwithstanding the
      idiosyncratic nature of US health care, and the implications this has for the
      generalizability of findings from the USA to other countries, it is pertinent to
      ask what other countries can learn from the US experience. Based on a series of
      structured interviews with leading experts on the US health system, this article
      draws out the key lessons for other countries as they develop similar policies in
      this area. This paper highlights three concerns that have dominated the
      development of adequate measures in the USA, and that require consideration when
      developing similar schemes elsewhere. Firstly, the need to develop indicators
      with sound metric properties - high in validity and meaningfulness, and
      appropriately risk-adjusted. Secondly, the need to involve all stakeholders in
      the design of indicators, and a requirement that those measures be adapted to
      different audiences. Thirdly, a need to understand the needs of end users and to
      engage with them in partnerships to increase the attention paid to measurement.
      This study concludes that the greatest challenge is posed by the desire to make
      comparative performance data more influential in leveraging performance
      improvement. Simply collecting, processing, analysing and disseminating
      comparative data is an enormous logistical and resource-intensive task, yet it is
      insufficient. Any national strategy emphasizing comparative data must grapple
      with how to engage the serious attention of those individuals and organizations
      to whom change is to be delivered.

PMID- 12180370
TI  - On the buzzword approach to policy formation.
AB  - This article draws attention to an absurd feature of contemporary political life
      that significantly affects health service policy and calls for an urgent
      explanation. Policies are formed by a process that privileges rhetoric over
      reality, producing policies that are conceptualized at a later date. Two
      influential articles on clinical governance illustrate this phenomenon perfectly.
      Lack of clarity about its true meaning and nature is a key feature of clinical
      governance. The lack of clarity allows policy-makers to shift responsibility for
      the problems of the health service onto the workforce, who are required to
      interpret the deliberately vague and platitudinous statements of management in
      order to implement the policy. But management, through the creation of monitoring
      agencies, reserves the right to determine whether the policy has been correctly
      interpreted, thus retaining power without responsibility. Government and senior
      management have abandoned the communicative function of language, eschewing
      reasoned debate (as characterized by the use of evidence and structured
      argument), instead employing language exclusively for the purposes of control and
      manipulation. Those of us still concerned that the future of our essential
      services should be determined by open and reasonable debate need to discuss
      urgently how to explain and respond to this appalling situation.

PMID- 12180368
TI  - When you hear hoofs, think horses, not zebras: an evidence-based model of health
      care accountability.
AB  - Health care organizations are increasingly asked to show accountability about
      their performance. This paper proposes that accountability can best be achieved
      through evaluative methods that are based on evidence regarding the relationship
      between processes of care and expected outcomes. Root cause analysis (RCA) is
      used as an illustration of how a generic method of inquiring can be transformed
      into an ongoing monitoring, evaluation, user education and accountability
      strategy. The role of performance indicators, as well as patient and community
      expectations, is discussed.

PMID- 12180371
TI  - Clinical governance: vision or mirage?
AB  - Clinical governance was intended to ensure clinical quality in the National
      Health Service. Its first full description, in the British Medical Journal in
      1998, seemed to some to be more rhetoric than substance. Now, 3 years on, its
      proponents believe it is starting to achieve its purpose. The British Medical
      Journal has again published a paper, this time subtitled 'turning vision into
      reality'. Expectations might have been that this paper would present evidence of
      how clinical governance is changing practice to ensure quality, but analysis of
      the paper shows that it does little more than repeat the rhetoric of the earlier
      description. It describes how clinical governance might be organized and what it
      might do, but not what it has done. Its authors repeat the idea that everyone can
      be 'the best' and achieve 'exellence', which is not reality at all. Anyone
      introducing a new method of managing the National Health System has the same
      obligation as those who introduce new treatments to provide evidence that the
      method works, and that the financial and non-financial costs are not too high.
      The new paper fails to provide that evidence.

PMID- 12180372
TI  - The evidence base for clinical governance.
AB  - RATIONALE, AIMS AND OBJECTIVES: Clinical governance has been advanced as a
      mechanism for continuous quality improvement within the UK National Health
      Service (NHS). This study aimed to assess whether evidence exists to support this
      claim. METHODS: A Medline search for evidence to link the introduction of
      clinical governance to improvements in the quality of health care was conducted.
      RESULTS: Of the 335 papers retrieved initially, 114 were potentially relevant to
      the question, but only 10 attributed changes in quality to clinical governance
      directly. Of these, only three attempted to provide data to support the
      assertion. CONCLUSION: No sound evidence currently exists to support the claim
      that clinical governance will increase service quality and moves towards its
      implementation must therefore be questioned.

PMID- 12180373
TI  - At what degree of belief in a research hypothesis is a trial in humans justified?
AB  - RATIONALE, AIMS AND OBJECTIVES: Randomized controlled trials (RCTs) have emerged
      as the most reliable method of assessing the effects of health care interventions
      in clinical medicine. However, RCTs should be undertaken only if there is
      substantial uncertainty about which of the trial treatments would benefit a
      patient most. The purpose of this study is to determine the degree of uncertainty
      in a research hypothesis before it can empirically be tested in an RCT. METHODS:
      We integrated arguments from three independent lines of research - on ethics,
      principles of the design and conduct of clinical trials, and medical decision
      making - to develop a decision model to help solve the dilemma of under which
      circumstances innovative treatments should be tested in an RCT. RESULTS: We
      showed that RCTs are the preferable option to resolve uncertainties about
      competing treatment alternatives whenever we desire reliable, undisputed, high
      quality evidence with a low likelihood of false-positive or false-negative
      results. CONCLUSIONS: When the expected benefit:risk ratio of a new treatment is
      small, an RCT is justified to resolve uncertainties over a wide range of prior
      belief (e.g. 10-90) in the accuracy of the research hypothesis. Randomized
      controlled trials represent the best means for resolving uncertainties about
      health care interventions.

PMID- 12180374
TI  - Birth odyssey.

PMID- 12180375
TI  - To screen or not to screen:  using spiral computerized tomography in the early
      detection of lung cancer.

PMID- 12180376
TI  - Helping patients search for meaning in their lives.

PMID- 12180377
TI  - Lessons from "over there": international approaches to HIV.

PMID- 12180378
TI  - Editorial: technical persistence.

PMID- 12180379
TI  - After the vaccine: the challenge of implementation.

PMID- 12180380
TI  - Understanding AIDS bereavement.

PMID- 12180381
TI  - Editorial: the normalizing of grief.

PMID- 12180382
TI  - Inducing wisdom: philosophical counseling for HIV-positive clients.

PMID- 12180383
TI  - Editorial: on the philosopher's couch.

PMID- 12180384
TI  - Rational suicide and the role of values.

PMID- 12180385
TI  - HIV, AIDS, and the distortion of science.

PMID- 12180386
TI  - Editorial: sense and credibility.

PMID- 12180387
TI  - Latino gay men and HIV: risk behavior as a sign of oppression.

PMID- 12180388
TI  - Editorial: institutionalized risk.

PMID- 12180389
TI  - The cultural scripts for Latino gay immigrants.

PMID- 12180390
TI  - HIV among African American men who have sex with men.

PMID- 12180391
TI  - Editorial: rationing benevolence.

PMID- 12180392
TI  - Responding to distrust of the medical system.

PMID- 12180393
TI  - Personality disorders and HIV disease: the borderline patient.

PMID- 12180394
TI  - Editorial: borderline prevention.

PMID- 12180395
TI  - The case of the HIV-positive borderline client.

PMID- 12180396
TI  - Report from the XIII International AIDS Conference. Psychosocial issues of the
      HIV pandemic in Africa.

PMID- 12180397
TI  - Editorial: into Africa.

PMID- 12180398
TI  - Living with HIV: prevention and care.

PMID- 12180399
TI  - Co-active coaching: an alternative to HIV-related psychotherapy.

PMID- 12180400
TI  - Coaching AIDS service organizations.

PMID- 12180401
TI  - Performance management.

PMID- 12180402
TI  - Training products of experts by minimizing contrastive divergence.
AB  - It is possible to combine multiple latent-variable models of the same data by
      multiplying their probability distributions together and then renormalizing. This
      way of combining individual "expert" models makes it hard to generate samples
      from the combined model but easy to infer the values of the latent variables of
      each expert, because the combination rule ensures that the latent variables of
      different experts are conditionally independent when given the data. A product of
      experts (PoE) is therefore an interesting candidate for a perceptual system in
      which rapid inference is vital and generation is unnecessary. Training a PoE by
      maximizing the likelihood of the data is difficult because it is hard even to
      approximate the derivatives of the renormalization term in the combination rule.
      Fortunately, a PoE can be trained using a different objective function called
      "contrastive divergence" whose derivatives with regard to the parameters can be
      approximated accurately and efficiently. Examples are presented of contrastive
      divergence learning using several types of expert on several types of data.

PMID- 12180403
TI  - Dynamic approximation of spatiotemporal receptive fields in nonlinear neural
      field models.
AB  - This article presents an approximation method to reduce the spatiotemporal
      behavior of localized activation peaks (also called "bumps") in non-linear neural
      field equations to a set of coupled ordinary differential equations (ODEs) for
      only the amplitudes and tuning widths of these peaks. This enables a simplified
      analysis of steady-state receptive fields and their stability, as well as
      spatiotemporal point spread functions and dynamic tuning properties. A lowest
      order approximation for peak amplitudes alone shows that much of the well-studied
      behavior of small neural systems (e.g., the Wilson-Cowan oscillator) should carry
      over to localized solutions in neural fields. Full spatiotemporal response
      profiles can further be reconstructed from this low-dimensional approximation.
      The method is applied to two standard neural field models: a one-layer model with
      difference-of-gaussians connectivity kernel and a two-layer excitatory-inhibitory
      network. Similar models have been previously employed in numerical studies
      addressing orientation tuning of cortical simple cells. Explicit formulas for
      tuning properties, instabilities, and oscillation frequencies are given, and
      exemplary spatiotemporal response functions, reconstructed from the low
      dimensional approximation, are compared with full network simulations.

PMID- 12180405
TI  - Robust blind source separation by beta divergence.
AB  - Blind source separation is aimed at recovering original independent signals when
      their linear mixtures are observed. Various methods for estimating a recovering
      matrix have been proposed and applied to data in many fields, such as biological
      signal processing, communication engineering, and financial market data analysis.
      One problem these methods have is that they are often too sensitive to outliers,
      and the existence of a few outliers might change the estimate drastically. In
      this article, we propose a robust method of blind source separation based on the
      beta divergence. Shift parameters are explicitly included in our model instead of
      the conventional way which assumes that original signals have zero mean. The
      estimator gives smaller weights to possible outliers so that their influence on
      the estimate is weakened. Simulation results show that the proposed estimator
      significantly improves the performance over the existing methods when outliers
      exist; it keeps equal performance otherwise.

PMID- 12180404
TI  - Independent components of magnetoencephalography: localization.
AB  - We applied second-order blind identification (SOBI), an independent component
      analysis method, to MEG data collected during cognitive tasks. We explored SOBI's
      ability to help isolate underlying neuronal sources with relatively poor signal
      to-noise ratios, allowing their identification and localization. We compare
      localization of the SOBI-separated components to localization from unprocessed
      sensor signals, using an equivalent current dipole modeling method. For visual
      and somatosensory modalities, SOBI preprocessing resulted in components that can
      be localized to physiologically and anatomically meaningful locations.
      Furthermore, this preprocessing allowed the detection of neuronal source
      activations that were otherwise undetectable. This increased probability of
      neuronal source detection and localization can be particularly beneficial for MEG
      studies of higher-level cognitive functions, which often have greater signal
      variability and degraded signal-to-noise ratios than sensory activation tasks.

PMID- 12180406
TI  - Joint entropy maximization in kernel-based topographic maps.
AB  - A new learning algorithm for kernel-based topographic map formation is
      introduced. The kernel parameters are adjusted individually so as to maximize the
      joint entropy of the kernel outputs. This is done by maximizing the differential
      entropies of the individual kernel outputs, given that the map's output
      redundancy, due to the kernel overlap, needs to be minimized. The latter is
      achieved by minimizing the mutual information between the kernel outputs. As a
      kernel, the (radial) incomplete gamma distribution is taken since, for a gaussian
      input density, the differential entropy of the kernel output will be maximal.
      Since the theoretically optimal joint entropy performance can be derived for the
      case of nonoverlapping gaussian mixture densities, a new clustering algorithm is
      suggested that uses this optimum as its "null" distribution. Finally, it is shown
      that the learning algorithm is similar to one that performs stochastic gradient
      descent on the Kullback-Leibler divergence for a heteroskedastic gaussian mixture
      density model.

PMID- 12180407
TI  - Sufficient conditions for error backflow convergence in dynamical recurrent
      neural networks.
AB  - This article extends previous analysis of the gradient decay to a class of
      discrete-time fully recurrent networks, called dynamical recurrent neural
      networks, obtained by modeling synapses as finite impulse response (FIR) filters
      instead of multiplicative scalars. Using elementary matrix manipulations, we
      provide an upper bound on the norm of the weight matrix, ensuring that the
      gradient vector, when propagated in a reverse manner in time through the error
      propagation network, decays exponentially to zero. This bound applies to all
      recurrent FIR architecture proposals, as well as fixed-point recurrent networks,
      regardless of delay and connectivity. In addition, we show that the computational
      overhead of the learning algorithm can be reduced drastically by taking advantage
      of the exponential decay of the gradient.

PMID- 12180408
TI  - Bayesian A* tree search with expected O(N) node expansions: applications to road
      tracking.
AB  - Many perception, reasoning, and learning problems can be expressed as Bayesian
      inference. We point out that formulating a problem as Bayesian inference implies
      specifying a probability distribution on the ensemble of problem instances. This
      ensemble can be used for analyzing the expected complexity of algorithms and also
      the algorithm-independent limits of inference. We illustrate this problem by
      analyzing the complexity of tree search. In particular, we study the problem of
      road detection, as formulated by Geman and Jedynak (1996). We prove that the
      expected convergence is linear in the size of the road (the depth of the tree)
      even though the worst-case performance is exponential. We also put a bound on the
      constant of the convergence and place a bound on the error rates.

PMID- 12180409
TI  - Training nu-support vector regression: theory and algorithms.
AB  - We discuss the relation between epsilon-support vector regression (epsilon-SVR)
      and nu-support vector regression (nu-SVR). In particular, we focus on properties
      that are different from those of C-support vector classification (C-SVC) and nu
      support vector classification (nu-SVC). We then discuss some issues that do not
      occur in the case of classification: the possible range of epsilon and the
      scaling of target values. A practical decomposition method for nu-SVR is
      implemented, and computational experiments are conducted. We show some
      interesting numerical observations specific to regression.

PMID- 12180410
TI  - On the problem in model selection of neural network regression in overrealizable
      scenario.
AB  - In considering a statistical model selection of neural networks and radial basis
      functions under an overrealizable case, the problem of unidentifiability emerges.
      Because the model selection criterion is an unbiased estimator of the
      generalization error based on the training error, this article analyzes the
      expected training error and the expected generalization error of neural networks
      and radial basis functions in overrealizable cases and clarifies the difference
      from regular models, for which identifiability holds. As a special case of an
      overrealizable scenario, we assumed a gaussian noise sequence as training data.
      In the least-squares estimation under this assumption, we first formulated the
      problem, in which the calculation of the expected errors of unidentifiable
      networks is reduced to the calculation of the expectation of the supremum of the
      chi2 process. Under this formulation, we gave an upper bound of the expected
      training error and a lower bound of the expected generalization error, where the
      generalization is measured at a set of training inputs. Furthermore, we gave
      stochastic bounds on the training error and the generalization error. The
      obtained upper bound of the expected training error is smaller than in regular
      models, and the lower bound of the expected generalization error is larger than
      in regular models. The result tells us that the degree of overfitting in neural
      networks and radial basis functions is higher than in regular models.
      Correspondingly, it also tells us that the generalization capability is worse
      than in the case of regular models. The article may be enough to show a
      difference between neural networks and regular models in the context of the least
      squares estimation in a simple situation. This is a first step in constructing a
      model selection criterion in an overrealizable case. Further important problems
      in this direction are also included in this article.

PMID- 12180412
TI  - Effects of quinine and quinidine on the transient outward and on the L-type
      Ca(2+) current in rat ventricular cardiomyocytes.
AB  - The effects of the enantiomers quinine and quinidine on the transient outward
      current (I(to)) and on the L-type Ca(2+) current (I(ca)) were investigated in rat
      ventricular cardiomyocytes using the patch-clamp technique. At a stimulation
      frequency of 2 Hz, both quinine and quinidine depressed the magnitude of I(to)
      and I(Ca); the half-maximal effects on I(to) were achieved at 11 and 15
      micromol/l, respectively, and those on I(Ca) at 14 and 10 micromol/l,
      respectively. At 0.2 Hz, both drugs depressed the magnitude of I(to), but not
      that of I(Ca). A change in extracellular pH from 7.3 to 8.3 did not significantly
      influence the effects of the drugs(which are protonated to 98% at pH 7.3) on
      I(to) or I(Ca). It is concluded that neither the different chemical structure nor
      the amount of protonation of quinine and quinidine controls their effects on
      I(to) or I(Ca).

PMID- 12180413
TI  - Role of seminal osmolarity in the reduction of human sperm motility.
AB  - Mammalian sperm at ejaculation are suspended in the seminal plasma, a
      heterogeneous mixture deriving from the testicular/epididymal fluid and from
      secretions of seminal vesicles, prostate and bulbourethral glands. Biochemical
      characteristics of seminal fluid change along the male reproductive tract when
      considering its inorganic and organic composition and pH but it is known that in
      each region of the male genital tract seminal osmolarity is higher than that of
      serum. It has been previously demonstrated that in invertebrate and vertebrate
      sperm, seminal plasma osmolarity influences sperm motility and activity, and
      human sperm have been shown to possess osmosensitive calcium entry pathway that
      controls important functions such as acrosome reaction and oocyte penetration. In
      the present study, we have determined seminal plasma osmolarity in a large number
      of normozoospermic fertile and asthenozoospermic infertile subjects correlating
      it with sperm motility percentages and kinematic characteristics determined
      utilizing a computerized motion analysis system. Our results confirm that seminal
      plasma osmolarity is higher than that of serum (336.1 +/- 20.2 vs. 291.1 +/- 6.9
      mOsm/L, respectively). Normozoospermic subjects show seminal osmolarity values
      that are significantly lower with respect to asthenozoospermic patients (317.8 +/
      12.2 vs. 345.2 +/- 22.6 mOsm/L, p<0.001), irrespective of the cause of
      asthenozoospermia. Seminal plasma osmolarity negatively correlates with sperm
      progressive motility percentages and kinetic characteristics (curvilinear
      velocity, linear velocity, linear coefficient and lateral displacements of sperm
      head). Furthermore, when sperm from fertile subjects were suspended in medium
      with an osmolarity increasing from 300 to 600 mOsm, sperm motility percentages
      and kinetics characteristics were progressively reduced and nearly abolished when
      medium osmolarity was 600 mOsm. On the contrary, when sperm from
      asthenozoospermic subjects with high semen osmolarity were resuspended in medium
      with lower osmolarity, sperm motility parameters improved significantly. Sperm
      motility parameters did not correlate with seminal plasma concentrations of
      sodium, potassium, chloride with a weak correlation only with seminal calcium
      concentration. No correlations are present between seminal plasma osmolarity and
      ionic composition. In conclusion, the present study confirms and extends the
      knowledge that, in human, seminal plasma osmolarity is higher than that of serum
      and demonstrates that seminal osmolarity influences sperm motility
      characteristics and then it may contribute to the pathogenesis of some forms of
      asthenozoospermia and male infertility.

PMID- 12180414
TI  - Providing dental services for people with disabilities: why is it so difficult?

PMID- 12180415
TI  - A civics lesson...and more.

PMID- 12180417
TI  - Why anaesthetising a patient is more prone to failure than flying a plane.

PMID- 12180416
TI  - Fiscal year 2001 Medicaid Home and Community-Based Services expenditures exceed
      those of ICFs/MR.

PMID- 12180418
TI  - Blood transfusion in patients with cardiac disease.

PMID- 12180419
TI  - Unrecognised fatal reaction to propofol or fentanyl.

PMID- 12180420
TI  - Deceptively well kept beard -- seeks attention.

PMID- 12180421
TI  - Re-useable and sheathed laryngoscope blades.

PMID- 12180422
TI  - Pre-operative airway evaluation.

PMID- 12180423
TI  - Pressure changes in tracheal tube cuffs at altitude.

PMID- 12180424
TI  - Cortical reflex myoclonus after propofol anaesthesia.

PMID- 12180425
TI  - An anaesthetists' role on labour ward.

PMID- 12180426
TI  - Cervical intraepithelial lesions and cervical cancer among Asian Pacific Islander
      women in a cervical cancer screening program.
AB  - Utilizing data from a cervical cancer screening program in California, we
      examined the relationship between being a woman of Asian/Pacific Islander (API)
      origin and receiving different types of abnormal cervical diagnoses. Initial
      descriptive data reflected a higher than expected percentage of API subjects with
      a final diagnosis of in situ and invasive cervical cancer when compared with
      other subjects in other ethnic groups (N = 2792). Results of multivariate
      analysis indicated that being of API origin retained significance in a model
      explaining the level of severity of the cervical final diagnosis, even when
      controlling for other significant predictors such as having a prior pap smear,
      age, referral source, the presence of cervical abnormalities and the time from
      screening to diagnosis. We conclude that women of API origin may not be accessing
      health care sufficiently early to prevent increasingly severe final diagnoses.
      Utilizing data from a cervical cancer screening program in California, we
      examined the relationship between being a woman of Asian/Pacific Islander (API)
      origin and receiving different types of abnormal cervical diagnoses. Initial
      descriptive data reflected a higher than expected percentage of API subjects with
      a final diagnosis of in situ and invasive cervical cancer when compared with
      other subjects in other ethnic groups (N = 2792). Results of multivariate
      analysis indicated that being of API origin retained significance in a model
      explaining the level of severity of the cervical final diagnosis, even when
      controlling for other significant predictors such as having a prior pap smear,
      age, referral source, the presence of cervical abnormalities and the time from
      screening to diagnosis. We conclude that women of API origin may not be accessing
      health care sufficiently early to prevent increasingly severe final diagnoses.

PMID- 12180427
TI  - The effects of an educational program for premenstrual syndrome of women of
      Korean industrial districts.
AB  - The purpose of this study is to find an intervention that will help alleviate
      women's signs and discomforts associated with premenstrual syndrome (PMS). As the
      social activities of women increase, eliminating PMS becomes increasingly
      important for many Korean women. A possible health care countermeasure for PMS is
      to assess PMS at an early stage; clarify the premenstrual signs, symptoms, and
      tensions; and afterward alleviate the premenstrual signs and discomforts. Related
      educational programs have been found to be effective interventions. Studies in
      Korea until now generally have focused on premenstrual signs and discomforts.
      This study, in contrast, was carried out in order to find women who have
      physical, mental, emotional, and behavioral discomforts due to PMS, then to
      provide them with an educational program, and eventually to establish an
      intervention that would help alleviate their premenstrual signs and discomforts.

PMID- 12180429
TI  - Current readings in nuclear medicine.

PMID- 12180428
TI  - Transgenic strategy for demonstrating nuclear reprogramming in the mouse.
AB  - Totipotency can be restored to the nuclei of somatic cells by reprogramming the
      nucleus via the technique of nuclear transfer. As genes expressed in somatic
      cells differ from those expressed in early embryos, a change in gene expression
      must accompany nuclear reprogramming. In this study, nuclear reprogramming of
      somatic cell nuclei following nuclear transfer (NT) was demonstrated by the
      reactivation of developmentally regulated lacZ reporter genes. NT embryos were
      generated by direct injection of adult cumulus cell nuclei into mature mouse
      oocytes from which maternal chromosomes were subsequently removed. Cumulus cells
      were collected from transgenic mice which show developmentally regulated lacZ
      reporter gene expression as a result of integration and functional coupling of
      reporter gene expression with the endogenous Oct4 or COB54 genes. As both genes
      are transcriptionally silent in somatic cells but are expressed during early
      embryonic development, reactivation of reporter gene expression in cumulus cell
      derived NT embryos was assessed as a means of monitoring nuclear reprogramming.
      The pattern of X-gal staining observed in individual NT embryos derived from both
      transgenic lines revealed that coordination of reactivation appeared to be
      specific for each gene, and that the timing of expression was consistent with
      that seen in control non-manipulated transgenic embryos. However, the staining in
      some NT embryos appeared to be diminished or absent. This reduction in staining
      may indicate a failure to reprogram gene expression in these embryos. Similar
      transgenic strategies employing lacZ vital stains, or alter-native reporters such
      as GFP, may facilitate real-time monitoring of reprogramming and a potential
      selection strategy to increase cloning efficiency through the identification and
      selection of reprogrammed, preimplantation stage NT embryos prior to embryo
      transfer.

PMID- 12180430
TI  - Bibliography. Current world literature. Hyperlipidaemia and cardiovascular
      disease.

PMID- 12180431
TI  - Pharmaceutical industry sets new guidelines for marketing to physicians.

PMID- 12180432
TI  - Effect of erythromycin on gastroduodenal contractile activity in developing
      neonates.

PMID- 12180434
TI  - Maxillary protraction.

PMID- 12180433
TI  - Colonic diversion for intractable constipation in children: colonic manometry
      helps guide clinical decisions.

PMID- 12180435
TI  - Ethical issues in endoscopic surgery.

PMID- 12180436
TI  - Intraoperative cholangiography during laparoscopic cholecystectomy.

PMID- 12180437
TI  - Induction of anti-RA33 hnRNP autoantibodies and transient spread to U1-A snRNP
      complex of spliceosome by idiotypic manipulation with anti-RA33 antibody
      preparation in mice.
AB  - OBJECTIVE: Anti-RA33 antibodies occur in patients with rheumatoid arthritis (RA),
      systemic lupus erythematosus (SLE), and mixed connective tissue disease (MCTD)
      and target the A2/B1 protein of the heterogeneous nuclear ribonucleoprotein
      (hnRNP) complex 4 which forms part of the spliceosome. The aim of the present
      study was to evaluate the immune response and pathological features induced in
      mice immunized with anti-RA33 antibodies or patient-derived recombinant single
      chain variable fragments (scFv) of anti-RA33 antibodies. METHODS: In the first
      set of the experiment, two strains of mice (C57BL/6J and BALB/c) were immunized
      with IgG preparations obtained from two patients with RA and one normal donor.
      One of the patients had high titer anti-RA33 antibodies; the other one showed
      weak borderline reactivity. In the second set of the experiment three groups of
      C57BL/6J mice were immunized, respectively, with affinity-purified (AP) anti-RA33
      antibodies, scFv of anti-RA33 antibodies and normal human IgG. The immunological
      response induced in immunized mice was studied by immunoblotting and line
      immunoassay (LIA). The presence of arthritis, serositis or myositis was assessed
      six-months following initial immunization. RESULTS: While anti-RA33 antibodies
      developed in only two of the mice immunized with different human IgG fractions,
      anti-RA33 antibodies were clearly detected in 7 sera of 13 mice immunized with AP
      anti-RA33 antibodies three months after the boost immunization and, moreover,
      also in 2 sera of 13 mice immunized with scFv of anti-RA33 antibodies. In
      contrast, mice immunized with normal human IgG did not develop anti-RA33
      antibodies. Interestingly, transient autoantibody production against another
      nuclear autoantigen, U1 snRNP, was observed in 3 C57BL/6J mice immunized with
      scFv and in 1 mouse immunized with AP autoantibodies. However, these
      immunological responses were not associated with pathological findings.
      CONCLUSIONS: Active immunization of naive mice with AP anti-RA33 antibodies and
      scFv of anti-RA33 antibodies resulted on the one hand in the production of murine
      anti-RA33 antibodies and led, on the other hand, to transient "autoantibody
      spread" to snRNP component of the spliceosome and other nuclear autoantigens.
      This "autoantibody spread" probably reflected disregulation of the idiotypic anti
      idiotypic cascade.

PMID- 12180439
TI  - Enabling evidence-based change in health care.

PMID- 12180438
TI  - Imaging evidence of successful multiple immunosuppressive treatment of cerebral
      involvement in Wegener's granulomatosis.

PMID- 12180440
TI  - Review: sildenafil improves sexual and erectile function in men.

PMID- 12180441
TI  - Review: antidepressants increase remission and clinical improvement in bulimia
      nervosa.

PMID- 12180442
TI  - Review: psychological treatment is as effective as antidepressants for bulimia
      nervosa, but a combination is best.

PMID- 12180444
TI  - Risperidone reduced the risk of relapse in outpatient schizophrenia and
      schizoaffective disorder.

PMID- 12180443
TI  - A school based psychosocial intervention was effective in children with
      persistent post-disaster trauma symptoms.

PMID- 12180445
TI  - A group of cognitive therapy programme reduced depressive episodes in at risk
      adolescents at 12 months of follow up.

PMID- 12180446
TI  - A behavioural management for continence intervention reduced urinary incontinence
      symptoms in older rural women.

PMID- 12180447
TI  - Naltrexone for 3 or 12 months in addition to psychosocial counselling did not
      reduce drinking in alcohol dependence.

PMID- 12180448
TI  - Review: methadone dose reduction is better than alpha2 adrenergic agonists for
      treatment retention in opioid dependence.

PMID- 12180449
TI  - Review: antidepressants are not effective for cocaine dependence.

PMID- 12180450
TI  - Review: dopamine agonists are not effective for cocaine dependence.

PMID- 12180451
TI  - A multidisciplinary community based rehabilitation programme improved social
      functioning in severe traumatic brain injury.

PMID- 12180452
TI  - Review: amisulpride is effective and safe for schizophrenia.

PMID- 12180453
TI  - Guided threat focus and reappraisal was better than safety seeking behaviour for
      reducing fear in claustrophobia.

PMID- 12180454
TI  - Intensive intervention for fear of childbirth did not reduce requests for
      caesarean section but decreased duration of vaginal labour.

PMID- 12180455
TI  - Review: selegiline leads to a small short term improvement in cognition and
      activities of daily living in Alzheimer's disease.

PMID- 12180456
TI  - The addition of olanzapine to valproate or lithium for acute manic or mixed
      bipolar episodes reduced manic symptoms.

PMID- 12180457
TI  - Extract of Ginkgo biloba added to haloperidol was effective for positive symptoms
      in refractory schizophrenia.

PMID- 12180458
TI  - 2 clock tests had high accuracy and naive raters had acceptable accuracy for
      detecting dementia.

PMID- 12180460
TI  - Mental disorders predicted all cause and cause specific deaths in Finnish adults.

PMID- 12180459
TI  - Review: major anxiety disorders all have substantive familial aggregation.

PMID- 12180461
TI  - High trait anger increased stroke in people </=60 years and those with high
      density lipoprotein cholesterol concentrations >47 mmol/l.

PMID- 12180462
TI  - Case management reduced hospital admission in caregivers of people with
      Alzheimer's disease.

PMID- 12180463
TI  - 4 thematic patterns described the experience of placing a relative with
      Alzheimer's disease in a special care unit.

PMID- 12180464
TI  - From logical neurons to poetic embodiments of mind: Warren S. McCulloch's project
      in neuroscience.
AB  - After more than half a century of eclipse, the mind (in contradistinction to
      brain and behavior) emerged in the 1950s as a legitimate object of experimental
      and quantitative research in natural science. This paper argues that the neural
      nets project of Warren S. McCulloch, in frequent collaboration with Walter Pitts,
      spearheaded this cognitivist turn in the 1940s. Viewing the project as a
      spiritual and poetic quest for the transcendental logos, as well as culturally
      situated epistemology, the paper focuses on McCulloch's and Pitts' efforts of
      logical modeling of the mind and on the social conditions that shaped that
      mission. From McCulloch's "experimental epistemology," the mind - purposes that
      ideas - emerged out of the regularities of neuronal interactions, or nets. That
      science of mind thus became a science of signals based on binary logic with
      clearly defined units of perception and precise rules of formation and
      transformation for representing mental states. Aimed at bridging the gulf between
      body and mind (matter and form) and the technical gulf between things man-made
      and things begotten, neural nets also laid the foundation for the field of
      artificial intelligence. Thus this paper also situates McCulloch;'s work within a
      larger historical trend, when cybernetics, information theory, systems theories,
      and electronic computers were coalescing into a new science of communication and
      control with enormous potential for industrial automation and military power in
      the Cold War era. McCulloch's modeling the mind as a system of command and
      control contributed to the actualization of this potential.

PMID- 12180465
TI  - The tortoise and the love-machine: Grey Walter and the politics of
      electroencephalography.
AB  - The life of the pioneer electroencephalographer, William Grey Walter, initially
      appears to be a paradigmatic example of the process of network building and
      delegation identified by Michel Callon and Bruno Latour. In his professional
      career, Walter continually repositioned himself, moving from an unhappy beginning
      as an expert in the apparently unless and suspect technology of the EEG, to
      become a self-styled crucial mediator in subjects as diverse as medical
      diagnosis, forensic detection, marriage counseling, and international diplomacy.
      This position was achieved moreover through the construction and co-option of
      human and mechanical accomplices - laboratory assistants, electrical tortoises,
      and mechanical analyzers - which sustained his research and propagated his
      arguments. However in contrast to Callon and Latour's atomistic account of
      scientific power and agency, this paper will extend their analysis to explore the
      impact of network building and delegation on domestic life, human desire, and
      personal identity. Walter's engagement with the complexities of love and the
      human brain demonstrates how the transformative power of scientific rhetoric
      extends simultaneously into both the organization of the world and the
      subjectivity of the individual.

PMID- 12180466
TI  - Techniques of the brain and the paradox of emotions, 1880-1930.
AB  - This essay studies the convergence of brain research with the physiology of
      emotions during the early twentieth century. It argues that the brain entered the
      laboratory of emotions not as an object of knowledge, but as a technique for
      producing emotions, in spite of the laboratory. The new brain-generated emotion
      signaled an epistemic break in the nature of studied emotion. It restructured the
      relationships between physiological and psychological forms of knowledge. It
      embodied the historical and political concerns of physiologists with pain. And it
      excluded the affectively experiencing subject from the study of "emotion." The
      essay also suggests that the brain-generated emotion was an object suspended in
      time and abstracted from history. Its unique a-temporal and de-contextualized
      characteristic transformed emotion into a product of a laboratory whose mode of
      production mimicked the modern factory. The constitutive elements that were
      assembled in creating the brain as emotion-generator were instrumental for the
      important studies of James Papez, Paul MacLean, and for the modern concept of
      Limbic System.

PMID- 12180467
TI  - Our traumatic neurosis and its brain.
AB  - During the nineteenth century, physicians either discovered or invented a variety
      of clinical autobiography called "traumatic memory." Freud produced two versions
      of this memory, the final version in the 1920s. A revolutionary nosology (DSM
      III), adopted in 1980, promised to extirpate Freud and the concept of neurosis
      from American psychiatry. However, it made a tacit exception for Freud's concept
      of traumatic neurosis, renaming it "postraumatic stress disorder." The following
      decades have been a period of intense clinical and scientific interest in this
      disorder. An influential research program has investigated traumatic neurosis and
      its brain through variations in cortisol excretion. I describe the history of
      this program, and examine its distinctive knowledge product. its running
      narrative of its achievements. The narrative's structure is analyzed and found to
      resemble a crossword puzzle constructed from heterogenous kinds of inference,
      recalling The Interpretation of Dreams. My conclusion is that, far from
      extirpating Freud's neurosis, biological research has secured a place for it in
      today's post-Freudian psychiatry.

PMID- 12180468
TI  - Bibliography of secondary sources on the history of dermatology. 1. Journal
      articles in English: supplemented through 2000.

PMID- 12180469
TI  - Hazardous materials: revision to standards for infectious substances. Final rule.
AB  - RSPA is revising transportation requirements for infectious substances, including
      regulated medical waste, to: adopt defining criteria and packaging requirements
      consistent with international standards; revise the current broad exceptions for
      diagnostic specimens and biological products; and authorize bulk packaging
      options for regulated medical waste consistent with requirements in international
      standards and DOT exemptions. These revisions will assure an acceptable level of
      safety for the transportation of infectious substances, and facilitate domestic
      and international transportation.

PMID- 12180470
TI  - Standards for privacy of individually identifiable health information. Final
      rule.
AB  - The Department of Health and Human Services ("HHS'' or "Department'') modifies
      certain standards in the Rule entitled "Standards for Privacy of Individually
      Identifiable Health Information'' ("Privacy Rule''). The Privacy Rule implements
      the privacy requirements of the Administrative Simplification subtitle of the
      Health Insurance Portability and Accountability Act of 1996. The purpose of these
      modifications is to maintain strong protections for the privacy of individually
      identifiable health information while clarifying certain of the Privacy Rule's
      provisions, addressing the unintended negative effects of the Privacy Rule on
      health care quality or access to health care, and relieving unintended
      administrative burdens created by the Privacy Rule.

PMID- 12180471
TI  - Toc, tic, and chloroplast protein import.
AB  - The vast majority of chloroplast proteins are synthesized in precursor form on
      cytosolic ribosomes. Chloroplast precursor proteins have cleavable, N-terminal
      targeting signals called transit peptides. Transit peptides direct precursor
      proteins to the chloroplast in an organelle-specific way. They can be
      phosphorylated by a cytosolic protein kinase, and this leads to the formation of
      a cytosolic guidance complex. The guidance complex--comprising precursor, hsp70
      and 14-3-3 proteins, as well as several unidentified components--docks at the
      outer envelope membrane. Translocation of precursor proteins across the envelope
      is achieved by the joint action of molecular machines called Toc (translocon at
      the outer envelope membrane of chloroplasts) and Tic (translocon at the inner
      envelope membrane of chloroplasts), respectively. The action of the Toc/Tic
      apparatus requires the hydrolysis of ATP and GTP at different levels, indicating
      energetic requirements and regulatory properties of the import process. The main
      subunits of the Toc and Tic complexes have been identified and characterized in
      vivo, in organello and in vitro. Phylogenetic evidence suggests that several
      translocon subunits are of cyanobacterial origin, indicating that today's import
      machinery was built around a prokaryotic core.

PMID- 12180472
TI  - The study of the radiation environment in near-earth space.
AB  - The report contains the description of the devices used for studying the
      radiation environment in space. They consist of passive dosimeters, a monitoring
      dosimeter and a spectrometer. Data were obtained with them over a long period of
      time. The analysis of these data permits one to conclude that radiation dose
      greatly depends on the apogee altitude and inclination; increasing the shield
      thickness does not greatly decrease the daily dose. The daily doses in orbits
      with an inclination of less than 65 degrees are 7 to 45 mrad day-1; the quality
      factor in those orbits was 1.2-1.4.

PMID- 12180473
TI  - The effect of ionizing radiations with different LET on survival and mutation in
      Chlorella.
AB  - The exposure of cells of Chlorella vulgaris LARG-I to radiations with a low LET
      (consisting of gamma-rays) yielded sigmoid dose-effect curves, whereas the action
      of radiations with a high LET (multiply charged ions of carbon C12(+6), boron
      B11(+2), neon Ne22(+4), argon Ar40(+8)) gave exponential curves. The rate of
      visible mutations depends directly on dose in the case of radiations with a low
      LET; it is a maximum after the action of radiations with a high LET. The highest
      RBE is shown by multiply charged ions of carbon (dE/dX 2850 MeV g-1 cm2). With
      dE/dX higher and lower than that of carbon ions the biological efficiency of
      radiations is less.

PMID- 12180474
TI  - Peculiarities of biological action of hadrons of space radiation.
AB  - Biological investigations in space enable one to make a significant contribution
      on high-energy hadrons to biological effects under the influence of factors of
      space flights. Physical and molecular principles of the action of high-energy
      hadrons are analysed. Genetic and somatic hadron effects produced by the
      secondary radiation from 70 GeV protons have been studied experimentally. The
      high biological effectiveness of hadrons, great variability in biological
      effects, and specifically of their action, are associated with strong
      interactions of high-energy hadrons. These are the probability of nuclear
      interaction with any atom nucleus, generation of a great number of secondary
      particles (among them, probably, highly effective multicharged and heavy nuclei,
      antiprotons, pi(-)-mesons), and the spatial distribution of secondary particles
      as a narrow cone with extremely high density of particles in its first part. The
      secondary radiation generated by high- and superhigh-energy hadrons upon their
      interaction with the spaceship is likely to be the greatest hazard of radiation
      to the crew during space flights.

PMID- 12180475
TI  - Some considerations of the theoretical limits for living organisms.
AB  - The study of the limits of life has been traditionally divided into two parts (a)
      extreme conditions for growth and metabolism, and (b) those conditions permitting
      survival in a dormant state. The variables most often considered have been
      temperature, radiation, availability of water and ageing. For growth and
      metabolism the most sensitive parts of living organisms appear to be those that
      involve labile metabolites, of which there is a great variety. For dormancy the
      stability of covalent bonds seems most important; here the C-C bond is likely to
      be less significant than C-O and C-N. But for both classes of damage the
      stability greatly depends on numerous factors (such as pH and oxygen
      concentration) that have seldom been considered in work so far. It is therefore
      desirable to explore the effects of combinations of adverse factors upon key
      metabolites and macromolecules. In addition, such studies may permit better
      estimates of the effects of very long time periods by extrapolation from
      experimental work.

PMID- 12180476
TI  - Membrane damage in dehydrated bacteria and its repair.
AB  - The dehydration of bacteria by vacuum exposure results in damage to the cell
      membrane. This membrane damage does not necessarily lead to cell death. A part of
      the dehydrated bacteria is capable of eliminating the membrane damage by repair
      processes. Repair can proceed rapidly under conditions that permit synthesizing
      activities. The kinetics of this repair process were studied by means of the
      membrane-mediated biosynthesis of the cell wall as well as by the recovery of
      resistance to small concentrations of lysozyme. Repair is a precondition for cell
      proliferation. At low temperature cells can conserve their membrane damage and
      the repair process can be initiated when conditions become favourable.

PMID- 12180477
TI  - VAD followed by VMCP: an alternative regimen for multiple myeloma.
AB  - In patients with multiple myeloma, a good complete response rate and disease-free
      survival may be achieved with sequential chemotherapy using VAD and VMCP, which
      is an alternative effective and less expensive treatment regimen. This regimen
      thus assumes particular significance in developing nations like India, where the
      majority of patients with myeloma cannot afford the cost of high-dose
      chemotherapy with stem cell rescue.

PMID- 12180478
TI  - Hodgkin's disease variant of Richter's transformation: a case report.
AB  - Hodgkin's disease rarely develops in patients with B-chronic lymphocytic
      leukemia. Patients developing Hodgkin's disease after the diagnosis of chronic
      lymphocytic leukemia have been called the "Hodgkin's disease variant of Richter's
      transformation." We present a 62-yr-old man with a 17-mo history of chronic
      lymphocytic leukemia, who clinically and hematologically on remission was
      admitted to our clinic because of rapidly developing right cervical
      lymphadenopathy. He was diagnosed with lymph node biopsy as a mixed-cellularity
      Hodgkin's disease.

PMID- 12180479
TI  - Simultaneous presentation of hepatocellular carcinoma in identical twin brothers.
AB  - Family history and hepatitis B virus (HBV) infection have been identified as risk
      factors for hepatocellular carcinoma. We report hepatocellular carcinoma (HCC)
      diagnosed at the same time in identical twin brothers. Serological analyses of
      the patients showed that both were chronically infected with HBV. Molecular
      analyses of the tumor specimens confirmed loss of heterozygocity of the Rb gene
      region. Both of the patients were unresponsive to chemotherapy and died within
      the same month with an interval of I wk. With a review of the current literature,
      we discuss the role of HBV infection and genetic factors on hepatic
      carcinogenesis.

PMID- 12180480
TI  - Flutamide-induced acute renal failure in a patient with metastatic prostate
      cancer.
AB  - Androgen blockage, with either orchiectomy or luteinizing hormone releasing
      hormone (LHRH) analogs combined with an antiandrogen drug, is the standard
      treatment for metastatic prostate cancer. Flutamide is a non-steroidal
      antiandrogen drug that is frequently used for total androgen blockage. We report
      on a 54-yr-old man with metastatic prostate cancer who developed nonoliguric
      acute renal failure (ARF) during treatment with flutamide. Following
      discontinuation of flutamide therapy, his renal functions returned to normal
      limits within 4 wk. After a rechallenge with flutamide, serum levels of BUN and
      creatinine increased again. His renal function recovered completely after the
      cessation of the drug for the second time. This observation confirm that ARF may
      be clearly attributed to flutamide therapy. Although very rare, flutamide-induced
      ARF should be considered.

PMID- 12180481
TI  - Tamoxifen-related porphyria cutanea tarda.
AB  - We report a case of porphyria cutanea tarda (PCT) in a patient with breast cancer
      following adjuvant tamoxifen. Cessation of tamoxifen resulted in a prompt decline
      in urinary porphyrins suggestive of a causative role. Tamoxifen is known to be
      hepatotoxic; however, its association with PCT is unclear. In this report, we
      discuss the porphyrinogenicity of tamoxifen and potential mechanisms.

PMID- 12180482
TI  - Skeletal muscle lymphoma.
AB  - Lymphoma usually presents with painless lymphadenopathy. However, it can also
      present at an extranodal site. Presentation with skeletal muscle infiltration is
      relatively uncommon and can be confused with a wide variety of both inflammatory
      as well as neoplastic conditions. We report a patient who presented with
      progressive swelling of the lower extremity resembling inflammatory necrosis on
      computed tomography scan, but was later diagnosed as skeletal muscle lymphoma on
      biopsy.

PMID- 12180483
TI  - Cancer patients undergoing chemotherapy show adequate serological response to
      vaccinations against influenza virus and Streptococcus pneumoniae.
AB  - Cancer patients receiving chemotherapy are prone to develop infections that might
      postpone treatment and lead to complications. The aim of our study was to
      investigate whether a heterogeneous population of patients with solid tumors and
      malignant lymphoma undergoing chemotherapy would respond serologically to
      vaccination against influenza and pneumococcal disease. There are no established
      routines in oncology departments in Norway regarding vaccination of these
      patients. The study included 35 cancer patients with median age 53 yr (range 20
      74) and 38 controls with median age 57 yr (range 43-75). The chemotherapy
      regimens used were mild or moderately immunosuppressive. After one vaccination,
      25 patients (72%) and 34 controls (87%) were serologically protected against two
      or three influenza strains. A higher proportion of patients with solid tumors
      (81%) than lymphoma (38%) achieved protection. Age, months on chemotherapy, and
      curative versus palliative treatment did not influence responses to vaccination.
      After vaccination with a 23-valent polysaccharide vaccine against pneumococci,
      most patients and controls achieved protective serum levels of antibodies against
      the different serotypes, with the exception that fewer patients were protected
      against serotype 4. The responses in controls were, however, generally stronger
      to all serotypes. Tumor type did not influence this vaccination response. We
      conclude that our cancer patients achieved adequate responses to influenza virus
      and Streptococcus pneumoniae. These are not live vaccines and are therefore safe
      for immunocompromised patients. Routine vaccinations against influenza virus and
      Streptococcus pneumoniae should be considered in cancer patients undergoing mild
      to moderately immunosuppressive chemotherapy.

PMID- 12180484
TI  - Negligible clinical effects of thalidomide in patients with myelofibrosis with
      myeloid metaplasia.
AB  - We conducted a nonrandomized prospective phase II study of thalidomide in anemic
      patients with myelofibrosis with myeloid metaplasia (MMM), with or without
      preceding polycythemia vera or essential thrombocythemia, with a primary aim to
      improve anemia. Thalidomide was given in escalating doses with a target dose of
      800 mg daily, but the median dose of thalidomide that was actually tolerated was
      400 mg daily. Fifteen patients were entered into the study and 14 were evaluable
      for response. Five of 14 (36%) patients discontinued thalidomide before 3 mo
      because of side effects, and none of these five patients had a response at the
      time when thalidomide was stopped. When evaluated after 3 mo of therapy, none of
      the remaining nine patients exhibited a discernible clinical response. Three
      patients showed progressive disease defined as > 50% increase in the need for red
      cell transfusions. Treatment was poorly tolerated, with all patients reporting
      side effects of thalidomide, the most prominent being fatigue documented in 80%
      of patients. Two patients died while on study, one from acute myelogenous
      leukemia and one from pneumonia. We conclude that thalidomide given in doses
      employed in the treatment of multiple myeloma gives no clinically relevant
      hematological effects in advanced MMM and is hampered by a very high incidence of
      side effects.

PMID- 12180486
TI  - Alemtuzumab, the first monoclonal antibody (MAb) directed against CD52.

PMID- 12180485
TI  - Expression of MDR1/P-glycoprotein, the multidrug resistance protein MRP, and the
      lung-resistance protein LRP in multiple myeloma.
AB  - The purpose of this study was to determine the incidence of three genes
      associated with multidrug resistance (MDR) in multiple myeloma in relation to
      treatment status. MDR1/Pgp (P-glycoprotein) expression was detected in 41% of 93
      myeloma samples. Generally, the incidence of MDR1/Pgp expression was higher in
      pretreated samples, and treatments with doxorubicin and/or vincristine were more
      effective in MDR1/Pgp expression than with alkylating agents. A significant
      association was observed between MDR1 /Pgp-positiveness and the ability of
      verapmil to increase doxorubicin sensitivity, suggesting functional relevance of
      MDR1/Pgp expression. MRP (multidrug resistance protein) expression was detected
      in 20.5% of 88 myeloma samples, in 26% at the mRNA level analyzed by quantitative
      reverse transriptase-polymerase chain reaction, and in only 3 of 79 samples by
      immunohistochemistry. LRP (lung-resistance protein) protein expression was
      observed in 12.5% of 72 myeloma samples. MRP and LRP expression was similar in
      samples with and without prior therapy. Approximately 80% of the myeloma samples
      with detectable mRNA expression of MDRI and MRP exhibited low expression levels
      corresponding to < 10% of the Pgp- and MRP-overexpressing multidrug-resistant
      human myeloma cell lines 8226/Dox6 and 8226/DOXint40c, respectively. Some normal
      bone marrow samples showed higher levels of MRP mRNA as compared to myeloma
      specimens, whereas MDRI mRNA expression in normal bone marrow was much lower (<
      or = 5%) than that in 8226/Dox6. These findings indicate a requirement to develop
      single-cell assays for MRP detection in multiple myeloma that are more sensitive
      than immunohistochemistry and might be useful to evaluate the incidence of genes
      associated with MDR.

PMID- 12180488
TI  - Clinical effects of alemtuzumab (Campath-1H) in B-cell chronic lymphocytic
      leukemia.
AB  - Alemtuzumab (Campath-1H) is a monoclonal antibody (MAb) that shows its most
      powerful effects in clearing malignant CD52-bearing cells from the blood and bone
      marrow. Attention had therefore focused on the use of alemtuzumab in the
      treatment of B-cell chronic lymphocytic leukemia (B-CLL), in which symptoms are
      the result of an expansion of a CD1a+/CD5+/CD23+/CD52+ malignant clone, causing
      lymphocytosis in the circulation and pervasive infiltration of the bone marrow.
      In clinical trials, in heavily pretreated patients, alemtuzumab was effective,
      producing responses in about one-third of patients who had failed to respond
      previously to chemotherapy, including fludarabine. In addition, there was an even
      higher clinical effect in the bone marrow. Alemtuzumab treatment has also allowed
      patients with advanced disease to proceed to stem cell transplantation, and
      preliminary data indicate that alemtuzumab is highly effective in previously
      untreated patients with B-CLL.

PMID- 12180487
TI  - Current and developing chemotherapy for CLL.
AB  - After several decades in which the standard treatment for chronic lymphocytic
      leukemia (CLL) was palliative, there is a shift toward intervention in patients
      with progressive disease. The introduction of the purine analogs has already seen
      great improvements in response rates, particularly when fludarabine is used in
      previously untreated patients. Combination chemotherapies, many of them based on
      fludarabine with alkylating agents or monoclonal antibodies, are continuing to
      improve the frequency, quality, and duration of responses.

PMID- 12180489
TI  - Alemtuzumab in T-cell malignancies.
AB  - Alemtuzumab is a humanized monoclonal antibody directed against the CD52 antigen,
      which is abundantly expressed on all normal and most malignant T-lymphocytes. We
      summarize the results of our experience using alemtuzumab to treat a range of
      clinically aggressive, mature, post-thymic, T-cell malignancies, including T-cell
      prolymphocytic leukemia (T-PLL), cutaneous T-cell lymphoma (CTCL), T-cell large
      granular lymphocyte (T-LGL) leukemia, and human T-cell lymphotropic virus I (HTLV
      I) associated adult T-cell leukemia-lymphoma (ATLL). Alemtuzumab was administered
      at a dose of 30 mg, three times a week until maximum response. Apart from first
      dose reactions, which were common, treatment was well tolerated, the main
      complication being infection and viral reactivation associated with the prolonged
      lymphopenia. Overall response rates were 76% (60% complete response) in 39
      patients with T-PLL and 100% in 3 patients with CTCL, of duration up to 4 yr.
      Experience in T-LGL and ATLL is limited to single cases only and further studies
      are required to better define the role of alemtuzumab in these subgroups. Our
      results indicate that alemtuzumab has activity in T-cell malignancies,
      particularly in T-PLL and in patients with predominantly blood and bone marrow
      disease. It may be possible to prolong response duration by the use of high-dose
      therapy and stem cell transplantation. Alemtuzumab may also have a role in
      purging minimal residual disease following other chemotherapy and prior to
      transplantation. We conclude that treatment with alemtuzumab may offer new hope
      to patients who otherwise have a bleak prognosis.

PMID- 12180490
TI  - A personal history of the CAMPATH-1H antibody.
AB  - The recent licensing of CAMPATH-1H (alemtuzumab) for the treatment of patients
      with refractory chronic lymphocytic leukemia has been the culmination of a long
      journey. This success is in large part due to the persistence, dedication, and
      commitment of a large number of academic collaborators. The first breakthrough
      was the identification of CAMPATH-1M, an isotype directed against CD52, and
      extremely efficient at lysing target cells in the presence of human complement,
      but limited in vivo by the rate of complement biosynthesis. The search for a
      monoclonal antibody that was more efficient in vivo found the rare class
      switching variant CAMPATH-1G, which is able to kill target cells by antibody
      dependent cell-mediated cytotoxicity. Construction of the humanized form of the
      antibody, CAMPATH-1H, and the development of resources to manufacture clinical
      grade material, further expedited many studies across the world in leukemia and
      lymphoma as well as in marrow transplantation, autoimmune disorders, and kidney
      transplantation. Such studies have taught us a lot about the diseases themselves,
      as well as offering the prospect of harnessing immunological tolerance processes
      to facilitate a whole new approach to immunosuppression.

PMID- 12180493
TI  - Future prospects for alemtuzumab (MabCampath).
AB  - In the treatment of hematological malignancies, the significance of achieving
      molecular complete remissions rather than a clinical complete remission has
      become increasingly apparent, as relapse is considered to be related to the
      presence and extent of residual, persistent malignant cells. Progress in the use
      of alemtuzumab (MabCampath) to eradicate minimal residual disease in chronic
      lymphocytic leukemia (CLL) has positive implications for patients, particularly
      prior to stem cell transplantation. Another beneficial aspect of monoclonal
      antibody therapy under active investigation is the ability of alemtuzumab to
      repeatedly produce or maintain responses. Subcutaneous administration of
      alemtuzumab is now emerging as a key advancement in the treatment of CLL. A phase
      II trial of subcutaneous alemtuzumab has demonstrated an 87% response rate in 38
      previously untreated patients, with a reduction in intravenous administration
      related rigors, as well as the elimination of nausea, dyspnea, diarrhea, and
      hypotension, frequently seen following intravenous administration of alemtuzumab.
      This trial demonstrates the advantages for safety, cost, flexibility, and
      convenience offered by subcutaneous administration of alemtuzumab. Finally,
      encouraging results with the combination of alemtuzumab and fludarabine, which
      demonstrate eradication of malignant cells in patients who are resistant to
      either agent alone, open the way for such combinations to produce durable
      responses even in refractory disease.

PMID- 12180492
TI  - Immunological effects and safe administration of alemtuzumab (MabCampath) in
      advanced B-cLL.
AB  - Alemtuzumab (MabCampath) can purge both B- and T-cells in a variety of clinical
      situations, as seen in the treatment of autoimmune disorders and of lymphoid
      malignancies such as B-cell chronic lymphocytic leukemia (B-CLL). One of the
      characteristics of advanced B-CLL is an increased susceptibility to infection,
      which may improve in patients whose disease responds to alemtuzumab, particularly
      when immune reconstitution by non-malignant stem cells is successful. However, at
      initiation of treatment, patients with advanced disease are likely to have poor
      immune function, and need careful management during and after treatment. Here, we
      present results showing the nature of immune reconstitution after alemtuzumab and
      the ways in which alemtuzumab may affect white cell counts during and after
      treatment. The management of B-CLL patients is discussed both in the context of
      minimizing acute "first-dose" events and with reference to the health risks
      already existing in this patient population. With protocols in place for dose
      escalation, for dose postponement in the event of cytopenia, and for anti
      infective prophylaxis, alemtuzumab can be used effectively and safely in high
      risk B-CLL patients.

PMID- 12180495
TI  - MK-383 (tirofiban) induces a GPIIb/IIIa receptor conformation which differs from
      the resting and activated receptor.
AB  - The platelet integrin alphaIIb beta3 (GPIIb/IIIa) acts as a receptor for
      fibrinogen, playing a critical role in platelet aggregation. GPIIb/IIIa
      antagonists, which block the receptor-ligand interaction, have been accused of
      causing occasional thrombocytopenia, probably via drug-induced platelet
      activation or immunogenic neoepitopes. We, therefore, analyzed the effects of the
      GPIIb/IIIa antagonist MK-383 (tirofiban) on platelet activation and GpIIb/IIIa
      conformation. At a concentration of 10(-7) mol/l, MK-383 completely inhibited
      fibrinogen binding to in vitro stimulated platelets. Simultaneously, the
      GPIIb/IIIa expression density increased, similar to that on activated platelets,
      but no effect on P-selectin expression or the formation of platelet-leukocyte
      aggregates could be observed, indicating that MK-383 binding did not induce
      general platelet activation. The GPIIb/IIIa receptor conformation was further
      analyzed by fluorescence resonance energy transfer analysis between fluorochrome
      labeled antibodies against different GpIIb/IIIa epitopes. As a result, MK-383
      induced a receptor conformation that differed from the resting as well as the
      activated receptor as induced by ADP or TRAP-6. This conformational modulation of
      GPIIb/IIIa presents an interesting mechanism which may be linked to receptor
      recruitment without inducing general platelet activation.

PMID- 12180491
TI  - Alemtuzumab in stem cell transplantation.
AB  - Alemtuzumab, otherwise called CAMPATH-1H, is a humanized monoclonal antibody
      directed against the CD52 antigen of lymphocytes. It is one of a family of
      CAMPATH-1 antibodies that have been used over the last 20 yr in stem cell
      transplantation for depletion of donor and recipient T-cells to prevent graft
      versus-host disease and graft rejection. Clinical trials have been carried out by
      a cooperative group of physicians and the protocols have gradually evolved as
      different problems have been identified and overcome. T-cell depletion carries
      risks of reducing graft-versus-tumor effects and increasing susceptibility to
      virus reactivation, but offers significant benefits in terms of reduced mortality
      and morbidity from graft-versus-host disease (GVHD). Two protocols are currently
      favored: (1) simple addition of CAMPATH-1H to the stem cell infusion and (2)
      administration in vivo prior to the transplant--especially in the context of
      nonmyeloablative conditioning regimens. Both of these give excellent control of
      GVHD with minimal graft rejection. Contrary to earlier expectations, a short
      course of posttransplant cyclosporin A (CyA) appears to further reduce transplant
      related mortality, mainly by a reduction in late deaths from infection. These
      results need to be consolidated by means of prospective clinical trials.

PMID- 12180494
TI  - Aspartame: review of safety.
AB  - Over 20 years have elapsed since aspartame was approved by regulatory agencies as
      a sweetener and flavor enhancer. The safety of aspartame and its metabolic
      constituents was established through extensive toxicology studies in laboratory
      animals, using much greater doses than people could possibly consume. Its safety
      was further confirmed through studies in several human subpopulations, including
      healthy infants, children, adolescents, and adults; obese individuals; diabetics;
      lactating women; and individuals heterozygous (PKUH) for the genetic disease
      phenylketonuria (PKU) who have a decreased ability to metabolize the essential
      amino acid, phenylalanine. Several scientific issues continued to be raised after
      approval, largely as a concern for theoretical toxicity from its metabolic
      components--the amino acids, aspartate and phenylalanine, and methanol--even
      though dietary exposure to these components is much greater than from aspartame.
      Nonetheless, additional research, including evaluations of possible associations
      between aspartame and headaches, seizures, behavior, cognition, and mood as well
      as allergic-type reactions and use by potentially sensitive subpopulations, has
      continued after approval. These findings are reviewed here. The safety testing of
      aspartame has gone well beyond that required to evaluate the safety of a food
      additive. When all the research on aspartame, including evaluations in both the
      premarketing and postmarketing periods, is examined as a whole, it is clear that
      aspartame is safe, and there are no unresolved questions regarding its safety
      under conditions of intended use.

PMID- 12180496
TI  - Regulation of platelet adhesion by oxidized lipoproteins and oxidized
      phospholipids.
AB  - Activated platelets adhere to the endothelium and release vasoactive mediators
      which induce vasoconstriction and remodeling of the vessel wall. The influence of
      native and ex vivo oxidized lipoproteins enriched with oxidized 1-palmitoyl-2
      arachidonoyl-sn-glycero-3-phosphorylcholine (ox-PAPC), the major lipid
      responsible for the biological activity of minimally oxidized LDL (mm-LDL), on
      platelet adhesion, membrane receptor expression and aggregation was studied.
      Influence of native and oxidized lipoproteins (5-100 microg protein/ml); ox-PAPC
      (0.5-50 microg/ml); ADP (1-10 microM) as well as the specific phosphatase 1 and
      2A inhibitor okadaic acid (3-10 microM) on platelet adhesion, receptor expression
      and aggregation was measured. Platelets adhered to all the classes of
      lipoproteins immobilized in plastic microtiter wells (native lipoproteins:
      HDL<LDL<VLDL<oxidized lipoproteins<ox-PAPC-enriched lipoproteins). Flow cytometry
      revealed that lipoproteins increased CD41 expression. Preincubation of platelets
      with ox-PAPC alone, significantly up-regulated CD62p and CD41 receptors (higher
      dose) but potently inhibited anti-CD36 MoAb binding. Okadaic acid increased anti
      CD41 and decreased anti-CD36 and anti-CD42b MoAbs binding. Neither ox-PAPC nor
      okadaic acid induced platelet aggregation. CD36 seems to be the main receptor
      responsible for binding of oxidized lipoproteins, particularly its ox-PAPC
      epitope. The effect of okadaic acid on CD36 and CD41 argue for the participation
      of phosphorylation-dependent reorganization of cellular trafficking and
      microtubule organization by ox-PAPC.

PMID- 12180497
TI  - Studies of fibrinogen binding to porcine platelets by flow cytometry: a method
      for studies of porcine platelet activation.
AB  - Platelets have a central function in haemostasis. They also participate in
      arterial thrombus formation in vascular disorders. Platelets have an important
      role in initiating and mediating ischaemia and related complications of ischemic
      heart disease. Several research groups are thus studying platelet activation and
      developing new platelet inhibitors. Platelet function is dependent upon membrane
      receptors and their interaction with other proteins. Binding of fibrinogen to the
      platelet glycoprotein (GP) IIb/IIIa receptor is a prerequisite for platelet
      aggregation and thrombus formation. Thus, several GPIIb/IIIa inhibitors have been
      developed of which abciximab is the clinically most widely used. Pigs are often
      used for experimental studies. We have developed a flow cytometry assay for
      measuring porcine platelet activation utilising an FITC-labelled chicken anti
      fibrinogen antibody. ADP, ristocetin and thrombin induce fibrinogen binding to
      porcine platelets similarly to human platelets. Ristocetin induces platelet
      aggregation and microvesicle formation from porcine platelets as well as from
      human platelets.

PMID- 12180498
TI  - Intracellular alkalinization augments platelet aggregation due to increase in
      cytosolic free-Ca2+.
AB  - Intracellular pH is known to increase during agonist-induced platelet activation.
      In order to elucidate the role of intracellular alkalinization in platelet
      activation, the effects of NH4Cl, as a tool to induce intracellular
      alkalinization, on ionomycin-induced platelet activation were investigated. NH4Cl
      (2.5-10 mM) concentration-dependently induced intracellular alkalinization.
      Platelet aggregation induced by ionomycin (0.1 microM) was augmented by treatment
      with NH4Cl (2.5-10 mM). Ionomycin-induced platelet aggregation in the absence of
      extraplatelet Ca2+, which was markedly attenuated compared to that in the
      presence of extraplatelet Ca2+, was also augmented by NH4Cl. NH4Cl treatment
      increased the number of large aggregates after ionomycin stimulation, while it
      decreased the number of small aggregates. Both transplasmalemmal Ca2+ entry and
      intracellular Ca2+ release induced by ionomycin were increased by treatment with
      NH4Cl (10 mM). SKF-96365 (100 microM), an inhibitor of receptor-operated Ca2+
      channels, did not affect ionomycin-induced Ca2+ entry but abolished the effect of
      NH4Cl on Ca2+ entry. Thus, NH4Cl augments receptor-operated Ca2+ channels and
      intracellular Ca2+ release. These findings suggest that intracellular
      alkalinization plays a significant role in agonist-induced platelet activation.

PMID- 12180499
TI  - Anti-platelet effects of different phenolic compounds from Yucca schidigera
      Roezl. bark.
AB  - Resveratrol (3,4',5-trihydroxystilbene) has been reported to have a variety of
      anti-inflammatory, anti-carcinogenic, anti-fungal and anti-platelet effects. It
      occurs naturally in different medicinal plants. Recently, resveratrol and other
      related phenolic compounds including trans-3,3',5,5'-tetrahydroxy-4'
      methoxystilbene and yuccaols A and C were isolated from the bark of Yucca
      schidigera. The aim of the present study was to evaluate in vitro the effects of
      these compounds on platelet aggregation induced by thrombin and ADP. Pretreatment
      of platelets with resveratrol or other tested phenolics (1-25 microg/ml) slightly
      reduced platelet aggregation stimulated by 5 microM ADP (P < 0.05) or 10 microM
      ADP (P < 0.005). The comparison of the inhibitory effects of tested compound in
      thrombin-induced platelet aggregation revealed that phenolic showed even stronger
      antiplatelet actions than resveratrol. These compounds also had an inhibitory
      effect on the thrombin-induced enzymatic platelet lipid peroxidation determined
      as the level of thiobarbituric acid reactive substances.

PMID- 12180500
TI  - Generation of reactive oxygen species in blood platelets.
AB  - The generation of superoxide anion radicals (O2*-) and the other reactive oxygen
      species (ROS) was estimated by means of cytochrome c reduction and
      chemiluminescence, as well in resting blood platelets and in platelets stimulated
      by thrombin in the presence or absence of some inhibitors of pathways involved in
      platelet activation. We used allopurinol (xanthine oxidase inhibitor), wortmannin
      (PI 3-kinase inhibitor) and staurosporine (protein kinase C inhibitor). To
      determine the involvement of the glutathione in ROS generation, we used L
      buthionine sulfoximine (BSO) which blocks GSH synthesis. Our results confirmed
      that thrombin stimulates the production of ROS concomitant with metabolism of
      arachidonate and production of malonyldialdehyde (MDA) in blood platelets (P <
      0.05) and showed that, in the presence of inhibitors, the generation of ROS in
      platelets (resting and stimulated) was reduced. This indicates that xanthine
      oxidase, PI 3-kinase or protein kinase C take part in the formation of ROS in
      blood platelets. Moreover, adhesion of platelets to fibrinogen and secretion of
      adenine nucleotides from platelets after wortmannin and staurosporine action was
      also inhibited. BSO not only decreased GSH level, but also reduced the amount of
      ROS; a correlation between the depletion of GSH and the decrease of ROS was
      observed (R = -0.987; P < 0.02). It is concluded that in blood platelets, ROS are
      produced in the receptor-mediated signaling pathways and platelet activation
      (arachidonic acid metabolism, the glutathione cycle, metabolism of
      phosphoinositoides and due to xanthine oxidase). Our results support the
      importance of ROS in platelet function.

PMID- 12180501
TI  - Development of thrombocytosis in HIV+ drug users: impact of antiretroviral
      therapy.
AB  - With the exception of hemolytic anemia, the potential hematological toxicity of
      antiretrovirals (ARV) and combination treatments in HIV treated individuals has
      not been well established. We report, for the first time, hematological toxicity
      defined as thrombocytosis in 9% of the HIV+ patients receiving highly active
      antiretroviral treatment (HAART) being followed in a nutritional clinical trial.
      Participants were evaluated every 6 months during a 2-year period (1998-2000) and
      blood drawn for biochemical, hematological and immunological parameters. NK cells
      were negatively correlated with platelet counts in the total cohort (P = 0.018)
      and persistently elevated with ARVT. Chronic thrombocytosis was associated with
      significantly lower NK percentages (P = 0.005). Twenty-five percent of the
      patients with thrombocytosis developed a cardiovascular disease. Together, these
      results support the proposal that HAART may increase the risk of hematological
      dysfunction and impact the risk of cardiovascular disease.

PMID- 12180502
TI  - Clopidogrel inhibits shear-induced platelet function.
AB  - We enrolled 17 healthy adult volunteers and measured platelet hemostasis time
      (PHT) and collagen-induced thrombus formation (CITF) before and after the oral
      administration of 300 mg of clopidogrel utilizing the Xylum Clot Signature
      Analyzer. We documented a statistically significant 30% prolongation of the PHT
      from 291+/-13 (SE) seconds to 376+/-31 (SE) s (P=0.037). There was a 7%
      prolongation of the CITF from 347+/-10 to 371+/-17 (SE) s (P=0.245). This study
      suggests that the Xylum Clot Signature Analyzer can measure changes in platelet
      function in response to a modest platelet inhibitor, and may be a useful clinical
      tool for the monitoring of antiplatelet therapies in patients.

PMID- 12180503
TI  - Ha'i ka mo'olelo ola: new developments in Native Hawaiian health.

PMID- 12180504
TI  - Sociocultural and community factors influencing the use of Native Hawaiian
      healers and healing practices among adolescents in Hawai'i.
AB  - Recently, there has been much emphasis placed on both alternative approaches to
      health care and the provision of culturally competent care. Despite these trends,
      few studies have examined the use of alternative therapies on the part of
      adolescents. Even fewer studies have been done focusing on traditional Hawaiian
      approaches to health care. This is essential, especially in Hawai'i, where
      Hawaiians have not attained health parity with other majority ethnic populations,
      despite significant efforts and funding to achieve this end. This study examines
      the sociocultural and community factors influencing the use of traditional Native
      Hawaiian healers and healing practices by adolescents in Hawai'i. The Hawaiian
      High Schools Health Survey was administered at five high schools on three islands
      in Hawai'i during the 1993-1994 school year. The sample included 1,321 high
      school students who preferred either an allopathic or alternative practitioner.
      Ethnicity, gender, community access, healer preference, health status, level of
      education, and health insurance status were used to predict healer use and
      participation in healing practices. Community access and healer preference
      predicted both healer use and participation in native healing practices. Mental
      health predicted healer use (i.e., seeing a Native Hawaiian healer in the past
      six months), but did not predict taking part in native healing practices, such as
      ho'oponopono and lomilomi. Hawaiian ethnicity, female gender, and a measure of
      health insurance predicted participation in native healing practices, but not
      healer use. These results suggest that native healing practices and traditional
      healers are being used in Native Hawaiian communities and this is perhaps not due
      to a lack of health insurance. Given the general separation between Western and
      Native Hawaiian health services, traditional healing practices should be made
      available in Native Hawaiian communities to see whether a collaboration between
      Western practitioners and traditional healers can have a greater positive impact
      on the health of Native Hawaiians, particularly for adolescents.

PMID- 12180505
TI  - Hawaiian health practitioners in contemporary society.
AB  - Hawaiian medical practices in Hawai'i became fragmented and deteriorated
      following the arrival of Western civilization. With the resurgence of Hawaiian
      pride, interest has risen to preserve what remains of Hawaiian healing methods.
      The purpose of this study is to determine the extent to which Hawaiian healing
      modalities are still in existence and practiced in the 1990s by Hawaiian health
      practitioners. Twenty-five Hawaiian health practitioners on the island of O'ahu
      agreed to in-depth interviews on their specific training and current practices of
      Hawaiian healing. Data collection included demographic characteristics, cultural
      attributes, training patterns, healing modalities, motivation to practice,
      spirituality and health, use of Hawaiian medicines, and training of haumana
      (students). Common practices as well as differences between practitioners and
      specialties were explored. This study found that a small, but substantive,
      component of Hawaiian healing is practiced by a growing number of Hawaiian
      practitioners. Content analyses identified two major components of Hawaiian
      healing: (1) attributes of Hawaiian culture, and (2) elements of spirituality in
      health and healing. Three significant modalities remain: ho'olomilomi, massage;
      la'au lapa'au, herbal medicine; and ho'oponopono, conflict resolution. Seventeen
      or 68% reported being skilled in more than one healing modality and 56% were
      training haumana. All practitioners reported apprenticeships under one or more
      master healers or a recognized elder healer--often a family member. Prior to, and
      after, the administration of any healing modality, spiritual blessings were
      administered by all practitioners to initiate the healing process and end the
      healing session. Hawaiian values--such as lokahi, harmony between man, nature,
      and the gods--are essential for holistic health. Without lokahi, there is
      illness. In summary, this study provides data that previously did not exist on
      contemporary Hawaiian health practitioners. Public health planners and health
      care professionals may find this information useful in developing culturally
      competent health programs for Hawaiian clients or patients.

PMID- 12180506
TI  - Health care utilization among women on O'ahu: implications for Native Hawaiian
      women.
AB  - Women generally seek and use more health care services than do men. Women are
      also more likely to encounter financial and non-financial barriers to care than
      do their male counterparts. These differences are accentuated among low income
      and minority women. We examined health care utilization patterns among women on
      O'ahu using survey data, and compared those patterns among Native Hawaiian and
      other ethnic groups. We also provide prevalence rates for several critical
      women's health issues by ethnic group and explore demographic predictors for
      health care utilization. Although the vast majority of women have seen health
      care providers in the last year, ethnic and socioeconomic disparities were
      identified, especially with respect to our Native Hawaiian female population. A
      pattern for Native Hawaiian women reveals among the highest rates of depression,
      as well as sexual/physical/emotional abuse. Alarmingly, Native Hawaiian women are
      also less likely to have seen a provider in the last year, less likely to have
      insurance coverage, and more likely to visit emergency departments. Differences
      by provider type served to reinforce these disparities. In order to reduce
      barriers to health care utilization for Native Hawaiian women--and for all women
      in Hawai'i--we recommend universal insurance coverage that includes screening and
      counseling services. Additionally, training for health care providers is
      essential in order to improve culturally competent, psychological assessments of
      health issues for women, particularly Native Hawaiian women.

PMID- 12180507
TI  - Ten-year changes in breast cancer knowledge, attitudes, and practices in Native
      Hawaiian women.
AB  - Compared to women in other ethnic groups, Native Hawaiian women have the highest
      breast cancer mortality rates in the state of Hawai'i. Nationally, the five-year
      relative survival rate for Native Hawaiian women is 9% shorter than for
      Caucasians and all races. This poor outcome has been attributed, in part, to late
      stage detection of cancer in Native Hawaiians, and data suggest that breast
      cancer screening rates for Native Hawaiian women are relatively low. This study
      examined breast cancer knowledge, attitudes, and practices (KAP) among Native
      Hawaiian women, reached through their friendship, community, and organizational
      networks. Response to an initial KAP survey in 1989-1990 was rewarded by a
      voucher for a free mammogram. Participation in both the survey (n = 903) and
      mammogram offer (n = 496) was high. The initial, Time 1 participants were
      resurveyed in 1999-2000, yielding a sample of 117 women who completed KAP surveys
      at both time points. After 10 years, changes in women's knowledge and attitudes
      were minimal. However, remarkable improvements in breast health practices were
      seen, with 62% of women reporting compliance with American Cancer Society
      guidelines for mammogram screening in 1999-2000, compared to only 14% in 1989
      1990. Findings suggest that breast health practices can be improved through
      appropriate outreach; encouragement by health professionals; and policies and
      programs that increase access and affordability.

PMID- 12180508
TI  - Treatment adherence to an antiretroviral regime: the lived experience of Native
      Hawaiians and kokua.
AB  - Treatment adherence to Highly Active Antiretroviral Therapy (HAART) is a critical
      issue in human immunodeficiency virus (HIV) care. HAART can extend the longevity
      of people living with HIV, but treatment efficacy relies on strict adherence that
      is difficult for many consumers to manage. Results presented in this article are
      based on semi-structured in-depth interviews with Native Hawaiian consumers (n =
      6) who reported moderate to low levels of overall HAART adherence, and based on
      their kokua, or primary support. All interviews were recorded on audiotape,
      transcribed verbatim, and analyzed using Grounded Theory methods. Research
      questions that guided the inquiry, included: What are the challenges of Hawaiians
      who report moderate to low levels of HAART adherence? How does non-adherence
      occur? What is the role of the kokua (primary caregiver) and/or family members in
      treatment adherence? What types of support enhance adherence? The
      unpredictability of living with HIV was a major challenge to adherence. Symptom
      distress and active use of alcohol and other drugs interfered with the capacity
      to appropriately adhere. Two patterns of non-adherence were identified:
      interrupted regime and intermittent use. Tangible and emotional types of support,
      sometimes delivered in culture-specific ways, were viewed as helpful in
      maintaining compliance and in resuming the regime when difficulties arose. The
      findings complement extant research on HAART by providing an understanding of
      adherence as a lived experience among Native Hawaiians and their kokua.

PMID- 12180509
TI  - Ka mauli o ka 'oina a he mauli kanaka: an ethnographic study from an Hawaiian
      sense of place.
AB  - Ka Mauli O Ka 'Aina A He Mauli Kanaka: The Life of the Land is the Life of the
      People. A sense of place has been directly linked to spiritual well being for all
      indigenous peoples. Yet, there is minimal evidence that demonstrates
      understanding and awareness of indigenous health issues from this perspective.
      Health, or the lack of it, appears to be related to place or the loss of it.
      Issues of Hawaiian health are inseparable from issues of land, water, and
      atmosphere. The purpose of this research study was to explore the experience of a
      sense of place and its relationship to health as perceived and experienced by
      Hawaiian participants living in Wai'anae, Hawai'i. Thirteen adult men and women,
      ranging in age from 36 to 80 years, participated in this ethnographic study. Two
      interviews conducted with each participant addressed the research question, "What
      is the experience of the relationship between a sense of place and health for
      Hawaiians?" Participants were also asked to photograph how they experienced this
      relationship. The qualitative data analysis computer software, Atlas.ti, was used
      to assist in data analysis. The findings suggest that the relationship between
      sense of place and health embodies four categories: (1) relationship to akua
      (god, spirit), (2) relationship to natural elements, (3) relationship to self and
      others, and (4) belonging to a particular place. Three major traditional Hawaiian
      concepts, which defined how the relationship between sense of place and health
      are experienced, were pono, mana, and kuleana. The relationship between these
      concepts revealed five cultural themes. Health for Hawaiians: I. is having a
      spiritual connection to their ancestral place; II. relates to the past, present,
      and future; III. is experienced with intention and understanding; IV. means an
      openness to the flow and use of energy; and V. is experienced as a pu'uhonua or
      safe place. These themes suggest implications for Hawaiian health education,
      practice, and further research, including that health professionals provide care
      from these perspectives in order to raise the health status of Hawaiians to the
      highest possible level. The limitations of the study suggest the uniqueness of
      Hawaiian communities and diversity of cultural traditions. Although responses
      from other communities will be valuable, an ethnographic study of one community
      (i.e., Wai'anae) provides the depth to understanding its people, place, patterns,
      and history. This study also engaged the community in selecting the participants.
      This allows for active involvement in the research process, particularly for this
      community, which has been a victim of this process in the past. The use of
      photography provided an excellent medium to capture the visual aspects of "place"
      creating a profound image of the relationship a person has with the land. Ka
      Mauli O Ka 'Aina A He Mauli Kanaka: The Life of the Land is the Life of the
      People.

PMID- 12180510
TI  - Native Hawaiian physician location and service to the underserved in Hawai'i.
AB  - This study examined the influence of demographic characteristics, training
      location, and "practice values" on geographic practice location and serving a
      medically underserved area/population (MUAP) among physicians of Native Hawaiian
      ancestry practicing within the State of Hawai'i. A survey assessing factors
      influencing practice location was mailed to 104 identified Native Hawaiian
      physicians in the State of Hawai'i with a response rate of 79% (n = 82). Factor
      analysis was used to identify underlying "practice value" variables important in
      physician practice location, resulting in three robust factors: (1) professional
      opportunity, (2) lifestyle, and (3) service. Data were analyzed using chi square,
      analyses of variance, and logistic regressions. Seventy-eight percent of the
      Native Hawaiian physicians sampled specialized in primary care, which is
      significantly more than in the general physician population in Hawai'i (57.3%)
      and in the continental United States (33.1%). Despite not being located in a
      MUAP, over half of the physicians felt that they provided important services to
      their medically underserved patients. Logistic regression models predicted 42% of
      the variance in practice location and 52% of the variance in serving a MUAP. In
      general, professional opportunity may be more important for non-MUAP physicians
      whereas service value may be more essential for MUAP physicians. Additional
      implications and further research are discussed.

PMID- 12180511
TI  - A profile of Hawaiians in the Medicaid Fee-For-Service program.
AB  - In Hawai'i, the Medicaid Fee-For-Service (FFS) program enrolled approximately
      39,000 individuals in fiscal year (FY) 1999. This program specifically provides
      healthcare services to enrollees classified as aged, blind, disabled, in-state
      foster children, and children who live out-of-state in subsidized adoptions. The
      total expenditure associated with this program was over $300 million in FY 1999.
      Nearly 4,600 enrollees in the Medicaid FFS program were self-identified as Native
      Hawaiians or part-Hawaiians. Although the proportion of Hawaiians in the Medicaid
      program was a fair representation of Hawaiians in the state, the distribution by
      recipient category within the program was in sharp contrast. Aged Hawaiians
      appeared to be under-represented in the program while disabled Hawaiians were
      overrepresented. Foster children and children under subsidized adoption accounted
      for 1% of the total Hawaiian population. Excluding the foster children and
      children under subsidized adoption, recipients of Hawaiian ancestry in the
      Medicaid FFS program (aged, blind, and disabled) obtained health care services
      amounting to approximately $34 million in FY 1999. Females in this population
      received more services, with total Medicaid payments amounting to $18.7 million.
      A higher proportion of Hawaiian recipients were on the neighbor islands. In this
      FFS Hawaiian population, the top three disease-states by dollar volume in FY
      1999, were Alzheimer's disease, acute cerebrovascular disease, and profound
      mental retardation. A total of $3 million in services were provided to recipients
      with these primary disease-states. The five leading disease-states facing
      Hawaiians were generally comparable to those confronting the overall FFS
      population.

PMID- 12180512
TI  - Eo na Mahu o Hawai'i: the extraordinary health needs of Hawai'i's Mahu.
AB  - An overview of health and social issues is presented here regarding Native
      Hawaiian transgenders. Perhaps due to relatively greater tolerance of gender
      diversity among Polynesian cultures, approximately 70% of all male-to-female
      transgenders in Hawai'i are Native Hawaiian. However, the overall climate is one
      of discrimination and harassment such that transgenders--who tend to be under
      educated, under-employed, and medically underserved--may be the most severely
      impacted of all Native Hawaiians. Lei Anuenue, human immunodeficiency virus (HIV)
      prevention program for Native Hawaiians, has provided a variety of services for
      transgenders, including outreach, educational workshops, support groups, HIV
      testing, and case management. All services are provided by peer leaders who are
      employed by the program. Data for this article are based on case management,
      including client self-disclosures and reports of peer staff who knew details of
      clients' lives having shared with them both generic experiences and specific
      activities. Information from 100 transgender clients and their case managers
      indicated that the transgender health profile is far more serious than that of
      mainstream Native Hawaiians. For example, 74% smoke, 31% use illegal drugs
      (excluding marijuana), more than 50% have been involved in street or domestic
      violence, and few individuals over age 50 have been found during three years of
      outreach. To some extent, employment options limit transgenders to prostitution,
      drug dealing, and minimum-wage jobs. In addition, a lifestyle of multiple sex
      partners and lack of opportunities for stable relationships place transgenders at
      much greater risk for HIV, sexually transmitted diseases (STD), and other
      infectious and non-infectious diseases as compared to the mainstream Native
      Hawaiian community. Clients in this study were from O'ahu, primarily from
      downtown Honolulu, Chinatown, and Wai'anae. Future studies should compare the
      results of this sample to transgenders from the neighbor islands (especially in
      rural Hawaiian areas), as well as utilize a structured prospective longitudinal
      approach.

PMID- 12180513
TI  - Kava as an anticraving agent: preliminary data.
AB  - Drug and alcohol abuse is one of the United States' most expensive and damaging
      health risk. The financial and social costs of addiction have led to a
      significant investment in prevention and treatment in an effort to reduce the
      incidence and prevalence of drug abuse. One important area of research is the
      chemistry of craving. It is assumed that if the neurological process of craving
      can be interrupted, then addiction can be successfully treated. The active
      ingredients found in kava, known as kavapyrones, have been found to bind to many
      sites in the brain that are associated with addiction and craving. In an effort
      to determine if kava can decrease the craving associated with substances of
      abuse, a craving survey and pilot study were completed where cravings of alcohol,
      tobacco, cocaine, and heroin were examined. The preliminary findings suggest that
      kava may reduce the craving associated with addiction. In one investigation, the
      participants reported a reduction in their desire for their drug of choice. In
      another investigation, a standardized amount of kavapyrones led to an apparent
      difference in abstinence between the experimental and placebo groups for alcohol.
      The studies presented are considered preliminary and exploratory, and intended
      only as a precursor to future, more systematic and large-scale investigations. If
      the findings are confirmed, kava may be a useful component to the treatment of
      addictions, especially for Native Hawaiian and Pacific peoples.

PMID- 12180514
TI  - Ethnic health data in Hawai'i: describing the databases.

PMID- 12180515
TI  - Hawai'i's first medical school. 1967.

PMID- 12180516
TI  - Genetic research and the vulnerability of Native Hawaiians.
AB  - Traditional research ethics are unable to provide adequate protections for human
      subjects involved in research--much less genetic research. New principles need to
      be developed to change the paradigm and put human research subjects in a more
      equitable relationship with their researchers. In addition, new laws should be
      crafted to level the playing field for human research participants. Humans can no
      longer look at themselves as hereditary beings, but as stewards of intra- and
      inter-generational genetic material in need of protection. Recommendations are
      provided.

PMID- 12180517
TI  - A call for respect and equality for indigenous scholarship in Hawaiian health.
AB  - In the State of Hawai'i, there has been steady interest on the part of Western
      scholarly communities in studies of indigenous Hawaiian intellectual properties.
      There exists an academic desire to appropriate new fields of knowledge from
      Hawaiian sources. This pursuit of knowledge runs the risk of increasing the sense
      of cultural violation already felt by many indigenous populations. If conducted
      using the means of colonialist intellectualism common to the academy of the
      dominant culture, this quest for new information will likely contribute to a
      legacy of spiritual and cultural violation felt by the Hawaiian people. This
      effort will then likely lead to a further decline in feelings of cultural
      integrity on the part of native populations. This endeavor will then increase the
      basis for the psycho-spiritual malaise that underpins the negative health
      statistics evidenced in Native Hawaiian populations. If present day researchers
      are to gain greater insight into the lexicon of knowledge available from Native
      Hawaiians, they will have to employ methods that provide for indigenous scholars
      to serve as co-researchers in this quest. If Western scholars are to gain access
      to Native Hawaiian knowledge, such information will more likely come as a result
      of healing this social wound by developing a new relationship of respect for
      Native Hawaiian cosmology, epistemology, and pedagogy--one wherein all parties
      are accepted as co-equals in the scholarly process.

PMID- 12180518
TI  - Reflections of a Native Hawaiian physician: Hawaiian cultural values in Western
      medical practice.
AB  - Native Hawaiians face challenges between their cultural upbringing and Western
      systems of learning. This paper describes my experiences of being a Native
      Hawaiian born and raised in Hawai'i and my path toward becoming a physician. This
      paper will reveal challenges of working within a Western educational system while
      remaining true to self and cultural values, and identifying ways to prosper in
      the medical profession while incorporating Native Hawaiian cultural values. In
      order to succeed in these areas, it is important to know oneself, to believe in
      oneself, to find a purpose and mission in life, and to appreciate and share one's
      gifts and talents. Awareness and acknowledgement of the differences between
      Western and Hawaiian beliefs is necessary to practice medicine in Hawai'i.

PMID- 12180519
TI  - Herbal medicine on the rise: the case of 'awa.
AB  - There has been increasing interest in 'awa on several levels (e.g., cultural,
      medicinal, economic). The present article explores the issues surrounding 'awa
      use, highlights existing literature, places the discussion in its proper
      indigenous context, and sheds light on the tensions fueled by culturally
      inappropriate practice. In concluding the article, recommendations within a
      native context are put forth in four domains: (a) education, (b) research, (c)
      analysis and implementation of legal protections, and (d) economic development.

PMID- 12180520
TI  - Cultural competence: a proposal for physicians reaching out to Native Hawaiian
      patients.
AB  - Many physicians of Native Hawaiian ancestry, as well as others, have noted a
      cultural gap between themselves and their Native Hawaiian patients. This cultural
      gap could potentially lead to discordance in the physician-patient relationship,
      and in turn, result in less than adequate therapeutic outcomes. Native Hawaiian
      physicians and those who treat Native Hawaiian patients are seeking ways to
      improve therapeutic relationships. Developing cultural competency in Native
      Hawaiian physicians and those who treat Native Hawaiian patients may be expected
      to improve therapeutic relationships. Principles of cultural competency,
      including increasing awareness of self and others, enhancing one's cultural
      knowledge base, and developing skills to communicate effectively, could be
      applied to physician-patient encounters with Native Hawaiian patients. The
      principles and skills of cultural competency could be learned during the formal
      and continuing medical education process. Developing an educational system that
      promotes cultural competency in physicians is necessary to address the health
      needs of Native Hawaiians and other diverse populations in Hawai'i.

PMID- 12180521
TI  - Uli'eo Koa--warrior preparedness.
AB  - The Uli'eo Koa Program was developed to study physiological and spiritual changes
      that occurred in a group of active Native Hawaiian adults participating in a
      specially designed, culturally appropriate exercise and diet intervention that
      approximated the training for Native Hawaiian warriors. Program components were
      physical exercise (including traditional Hawaiian lua [fighting art]), a
      traditional Hawaiian diet (THD), lomilomi (Hawaiian massage), and a culturally
      rich health education program for active Native Hawaiian adults. Periodic
      assessments of muscle strength/fitness, flexibility, body composition, weight,
      body mass index, as well as other indicators, were compared to current standards
      of clinical medicine and science related to physical performance. Differences
      observed from baseline to post-intervention suggested that the Uli'eo Koa Program
      may be effective in improving the health of Native Hawaiians. Limitations and
      clinical implications of the study are discussed.

PMID- 12180522
TI  - Uli'eo Koa Program: incorporating a traditional Hawaiian dietary component.
AB  - Traditional Hawaiian Diet (THD) programs were developed over the past 15 years as
      a culturally appropriate community intervention for improving the health status
      of Native Hawaiians. THD programs are generally three weeks in length and
      incorporate a diet regimen of foods traditional to the Hawaiian culture, coupled
      with an education component that emphasizes cultural beliefs and practices that
      support health and wellness. In accordance with traditional practice, THD meals
      consist mainly of vegetable foods, with controlled amounts of protein. THD
      programs have demonstrated high success in weight reduction of severely
      overweight individuals, as well as reductions of serum cholesterol,
      triglycerides, glucose, and blood pressure. THD programs, to date, have focused
      on the reduction of these risk factors. The Uli'eo Koa Program, Warrior
      Preparedness Program, is a pilot study that incorporated a traditional Hawaiian
      diet component to ascertain its effects on a group of moderately active, non
      obese Native Hawaiian adults--specifically the diet's contribution to wellness
      and physical fitness. Other components of the Uli'eo Koa Program were a physical
      exercise regimen and a traditional healing component. The purpose of the dietary
      component of the Uli'eo Koa Program was to provide the nutritional support needed
      to sustain nutritional requirements for increased physical activity within this
      group. The year-long Uli'eo Koa Program consisted of three phases. In Phase I,
      exercise was conducted twice a day and three meals, including snacks, were
      provided for participants over a three-week period. During Phase II, structured
      exercise time and meals were decreased to three times a week and two times a
      week, respectively, for eight weeks. Participants were responsible for
      maintaining these regimens on their own outside of the structured activities. In
      Phase III (in progress at the time of this manuscript preparation), the remainder
      of the program year, participants were solely responsible for structuring their
      own physical and dietary behaviors. The nutrient composition of the meals
      followed a traditional Hawaiian diet, which was typically high in complex
      carbohydrates, low (< 10%) in total dietary fat and limited in protein (as
      compared to a standard American diet). Dietary assessments were conducted at the
      onset (baseline) of the program, using a 24-hour dietary recall methodology. When
      the post-dietary assessments, conducted at the end of Phase II, were compared to
      the baseline assessments, positive results were indicated by the reported
      increases in intakes of all major nutrients, including key vitamins and minerals
      required for exercise. A final dietary assessment will be conducted at the end of
      the program year (Phase III) to determine maintenance of positive dietary habits.
      Implications and future research are discussed.

PMID- 12180523
TI  - Validating a measure of religiousness/spirituality for Native Hawaiians.
AB  - Religiousness and spirituality are integral to the human experience. There is
      emerging literature that shows that religiousness and spirituality are associated
      with various mental and physical health outcomes. Yet, the development of
      measures to accurately assess these phenomena in health settings is still in its
      early stages. The difficulties in developing standardized definitions and
      measures relate to varying interpretations of religiousness and spirituality, a
      reluctance to utilize a scientific approach to understand an existential and
      personal experience, and multicultural distinctions. The potential for designing
      health interventions in which religiousness and spirituality are integrated rests
      upon the development of measures that are psychometrically sound. This paper
      reports on preliminary research that empirically assesses one measure of
      religiousness and spirituality for Native Hawaiians--a group besieged with an
      array of health problems. The measure is the Brief Multidimensional Measure of
      Religiousness/Spirituality (BMMRS) developed by the National Institute on Aging
      and the Fetzer Institute. This instrument has shown to have appropriate
      reliability and validity scores. A modified BMMRS was administered to 15 Native
      Hawaiians who underwent a cultural intervention of exercise, diet, and education
      in a program called Uli'eo Koa (warrior fitness). The BMMRS was slightly modified
      based on the literature and earlier research to be more specific to Native
      Hawaiians. Overall, measures of internal consistency supported the reliability of
      the BMMRS. The strongest subscales included the domains of "daily spiritual
      experiences," "religious and spiritual coping," and "religious support." Low
      internal consistency estimates for the items, "watches/listens to religious
      programs," "family makes demands," and "significant loss in faith," suggest that
      these items do not measure the same concept for participants. Although the
      intercorrelations among the subscales were generally low and with wide
      variability, 10 of the 17 subscales/single items were moderately to highly
      correlated with one another, indicating concurrent validity. These subscales,
      some of which assessed, "daily spiritual experiences," "religious and spiritual
      coping," and "organizational religiousness," suggest that core ideas on
      spirituality and religiousness for these participants, broadly reflect both
      "personal" and "organizational" viewpoints. Caution should be used in
      interpreting the results of the study because of limitations in the study's
      design. However, despite these limitations in design, this study provides
      empirical support for future research on religiousness and spirituality for
      Native Hawaiians.

PMID- 12180524
TI  - O Ke Aloha Ka Mea I Ho'ola 'Ai--Compassion Is the Healer: an indigenous peoples
      healing conference. October 2000, Hawai'i.

PMID- 12180525
TI  - Utilizing cultural immersion in a cultural competency curriculum: a conference
      report.
AB  - Overall, the evaluations of the conference were excellent and the speakers
      received high marks. Many participants were deeply moved and eager to share what
      they learned with colleagues and family. The constructive comments centered on
      the large number of topics covered in a short time. Requests that we decrease the
      number of speakers and increase the amount of time for discussion will be
      addressed in the planning of what will hopefully be another similar program next
      year. In summary, based on this experience, adding a cultural immersion
      experience to a cultural competency curriculum can be very successful because
      this approach enables learning to occur on several levels, not just from sitting
      in a lecture but through actual experiences of the culture--physically,
      emotionally, and spiritually.

PMID- 12180526
TI  - Treating and counseling people of colour conference: a Native Hawaiian
      perspective.

PMID- 12180527
TI  - 5th International Conference on Diabetes and Indigenous Peoples. Christchurch,
      New Zealand. October 2000.

PMID- 12180528
TI  - 'Imi Hale: establishing an inheritance for Native Hawaiians on cancer awareness,
      research and training.
AB  - Native Hawaiians experience disproportionate rates of cancer incidence and
      mortality both nationally and in their homeland, Hawai'i. 'Imi Hale--the Native
      Hawaiian Cancer Awareness, Research, and Training Project, a five-year project
      funded by the National Cancer Institute, is aimed at reducing the burden of
      cancer among Native Hawaiians. The project's overall goal is to reduce cancer
      incidence and mortality among Native Hawaiians through the establishment of a
      sustainable infrastructure to 1) promote cancer awareness within Native Hawaiian
      communities, and 2) initiate cancer research, training, and control activities. A
      community-based project, 'Imi Hale emphasizes community participation, respect
      for cultural values, and the sharing of information, as we believe that a
      commitment to involve Native Hawaiians in all activities of the project will help
      assure that the community's awareness, training, and research priorities are
      addressed. In the first year of operation, cancer awareness activities included
      the development of culturally sensitive booklets on breast cancer and the
      provision of cancer education and screening for members of the Association of the
      Hawaiian Civic Clubs. Research and training activities included focus groups to
      explore the perceptions and experiences of cancer survivors, surveys to assess
      research priorities, the identification of Native Hawaiian researchers and the
      development of pilot research projects. The work of 'Imi Hale is guided by the
      hope that Native Hawaiians can reverse the negative effects of cancer and leave a
      powerful legacy and inheritance for future generations based on good health and
      well-being. 'Imi Hale means "to establish, as a dynasty; to acquire authority,
      power; to seek and establish an inheritance for one's children; and to form a
      friendship so close that one feels welcome in the house of the other." "By using
      our language for a name, we are invoking and honoring our ancestors, our culture,
      language and restoration as a nation."

PMID- 12180529
TI  - Imi Ho'ola post-baccalaureate program: recruitment, retention, and graduation of
      Asian American and Pacific Islander students in medicine.
AB  - Imi Ho'ola has been a successful model for training underrepresented minorities
      and disadvantaged individuals in medicine at the University of Hawai'i. This
      program has 28 years of experience assisting students to prepare for, qualify
      for, and complete the M.D. program, thereby producing medical doctors and other
      health professionals for Hawai'i, Guam, American Samoa, the U.S. Associated
      Pacific Islands (USAPI), and the continental U.S. Recently, Imi Ho'ola has
      expanded its outreach efforts to create an educational pathway for local high
      school and college students encouraging them to pursue higher education and
      health careers. A description of the Imi Ho'ola is presented with emphasis on its
      post-baccalaureate curriculum begun in 1995.

PMID- 12180530
TI  - The Native Hawaiian Health Professions Scholarship program's impact on the
      community of Ko'olau Loa: a program report.
AB  - The Native Hawaiian Health Professions Scholarship was established as one
      component of the Native Hawaiian Health Care Act of 1988, which was later
      reauthorized as the Native Hawaiian Health Care Improvement Act of 1992. The
      Scholarship program was designed to develop Native Hawaiian primary health care
      professionals who would return to work in Native Hawaiian communities. To ensure
      this, scholarship recipients fulfill their scholarship agreement by working in
      medically unserved and underserved communities throughout Hawai'i. Since 1991,
      121 scholarships have been awarded to Native Hawaiians training in different
      primary care professions including medicine, dentistry, nursing, midwifery,
      social work, and public health. Although the service obligation is attached to
      the scholarship as a means of "paying back," the intent is to provide an
      opportunity for graduates to establish a sense of social responsibility for the
      communities most in need. One of the communities benefiting from this program is
      Ko'olau Loa, a community that spans from Ka'a'awa to Pupukea on Windward O'ahu.
      Native Hawaiian Health Scholarship recipients, Kehau Santiago, Michele Shimizu,
      and Stephany Vaioleti live and continue to serve in the very community in which
      they fulfilled their service obligations. This article focuses on how the Native
      Hawaiian Health Scholarship Program--in particular, the three scholars--affected
      Ko'olau Loa.

PMID- 12180531
TI  - Lunalilo Home reopens.

PMID- 12180532
TI  - Evaluation of the AERx pulmonary delivery system for systemic delivery of a
      poorly soluble selective D-1 agonist, ABT-431.
AB  - PURPOSE: ABT-431 is a chemically stable, poorly soluble prodrug that rapidly
      converts in vivo to A-86929, a selective dopamine D-1 receptor agonist. This
      study was designed to evaluate the ability of the AERx pulmonary delivery system
      to deliver ABT-431 to the systemic circulation via the lung. METHODS: A 60%
      ethanol formulation of 50 mg/mL ABT-431 was used to prepare unit dosage forms
      containing 40 microL of formulation. The AERx system was used to generate a fine
      aerosol bolus from each unit dose that was collected either onto a filter
      assembly to chemically assay for the emitted dose or in an Andersen cascade
      impactor for particle size analysis. Plasma samples were obtained for
      pharmacokinetic analysis after pulmonary delivery and IV dosing of ABT-431 to
      nine healthy male volunteers. Doses from the AERx system were delivered as a
      bolus inhalation(s) (1, 2, 4, and 8 mg) and intravenous infusions were given over
      1 hr (5 mg). Pharmacokinetic parameters of A-86929 were estimated using
      noncompartmental analysis. RESULTS: The emitted dose was 1.02 mg (%RSD = 11.0, n
      = 48). The mass median aerodynamic diameter of the aerosol was 2.9 +/- 0.1 microm
      with a geometric standard deviation of 1.3 +/- 0.1 (n = 15). Tmax (mean +/- SD)
      after inhalation ranged from 0.9 +/- 0.6 to 11.5 +/- 2.5. The mean absolute
      pulmonary bioavailibility (as A-86929) based on emitted dose ranged from 81.9% to
      107.4%. CONCLUSIONS: This study demonstrated that the AERx pulmonary delivery
      system is capable of reproducibly generating fine nearly monodisperse aerosols of
      a small organic molecule. Aerosol inhalation utilizing the AERx pulmonary
      delivery system may be an efficient means for systemic delivery of small organic
      molecules such as ABT-431.

PMID- 12180533
TI  - Characterization of mefenamic acid-guaiacol ester: stability and transport across
      Caco-2 cell monolayers.
AB  - PURPOSE: Prodrug of non-steroidal anti-inflammatory drugs (NSAIDs) or NSAIDs
      linked with guaiacol have been reported to suppress gastrointestinal (GI)
      toxicity or induce GI protective effect. In this study. mefenamic-guaiacol ester
      was synthesized and its physicochemical properties. stability, and transport
      across Caco-2 monolayers were investigated. METHODS: Synthesis of the ester was
      carried out using mefenamic acid, guaiacol. N. N'-dimethylaminopyridine, and
      N,N'dicyclohexylcarbodiimide. The hydrolysis of the ester was investigated in
      aqueous buffer solutions pH 1-12 as well as in Caco-2 homogenate, human plasma,
      and porcine liver esterase. Caco-2 cell monolayers were utilized for transport
      studies. Due to the high lipophilicity of the ester with a calculated logP of
      6.15, bovine serum albumin (BSA, 4%) was included in the receiver compartment to
      obtain a good in vitro-in vivo correlation. Permeation of the ester was assessed
      with or without the exposure of cells to PMSF, an inhibitor of esterase. RESULTS:
      The ester was stable at a wide pH range from 1-10. However, it was hydrolyzed by
      enzymes from porcine liver esterase and Caco-2 homogenate. With the PMSF exposure
      on the apical (AP) side and in the presence of 4% BSA on the basolateral (BL)
      side, the transported amount of the ester from AP-to-BL direction was 14.63%
      after 3 hr with a lag time of 23 min. The Papp for the ester was 4.72 x 10(-6) cm
      s(-1). CONCLUSION: The results from hydrolysis studies indicate that this ester
      is a prodrug. The Papp value suggests the moderate absorption characteristic of
      the compound. The accumulation of this highly lipophilic ester in Caco-2 cells is
      reduced in the presence of BSA.

PMID- 12180535
TI  - Influence of structural variations in peptidomimetic 4-amidinophenylalanine
      derived thrombin inhibitors on plasma clearance and biliary excretion in rats.
AB  - PURPOSE: Systemic and hepato-biliary clearance of peptidomimetic thrombin
      inhibitors of the 4-amidinophenylalanine amide-type, derived from NAPAP (Nalpha
      [2-naphthylsulfonyl-glycyl]-4-amidinophenylalanine-piperidide) by substituting
      Gly in P2 for natural and unnatural amino acids or by varying the C- and N
      terminal moieties. resp., were investigated. METHODS: Concentrations of the
      compounds administered as intravenous bolus injection at a dose of 1 mg/kg to
      bile duct-cannulated rats were determined in plasma and bile samples collected
      over 4 hours using reversed-phase HPLC. RESULTS: NAPAP and the derivatives with
      additional charged groups are comparatively hydrophilic compounds. For NAPAP and
      most of the derivatives the biliary clearance accounted for a high percentage of
      the rapid systemic plasma clearance. Derivatives 2a-c with a second basic group
      in P2 position showed lower systemic and biliary clearance compared to NAPAP,
      whereas their cumulative biliary excretion after a period of 120 min was less
      affected. Bis-benzamidine derivatives 4a and 5 with the second amidino group in
      the N-terminal moiety had the lowest biliary clearance. Additional carboxylic
      groups reduced the systemic and biliary clearance only as free
      amidinophenylalanine carboxyl in 3a and 5. No influence compared to NAPAP was
      observed for 2d with a free carboxyl group in P2 position. CONCLUSIONS: The weak
      correlation of the log P values of the compounds with the clearance parameters
      indicates the influence of structural variations, especially of charged groups,
      in this series of compounds rather than overall lipophilicity on hepato-biliary
      elimination mediated by hepatocellular transporters.

PMID- 12180534
TI  - Modifying the bitterness of selected oral pharmaceuticals with cation and anion
      series of salts.
AB  - PURPOSE: NaCl has proven to be an effective bitterness inhibitor, but the reason
      remains unclear. The purpose of this study was to examine the influence of a
      variety of cations and anions on the bitterness of selected oral pharmaceuticals
      and bitter taste stimuli: pseudoephedrine, ranitidine, acetaminophen, quinine,
      and urea. METHOD: Human psychophysical taste evaluation using a whole mouth
      exposure procedure was used. RESULTS: The cations (all associated with the
      acetate anion) inhibited bitterness when mixed with pharmaceutical solutions to
      varying degrees. The sodium cation significantly (P < 0.003) inhibited bitterness
      of the pharmaceuticals more than the other cations. The anions (all associated
      with the sodium cation) also inhibited bitterness to varying degrees. With the
      exception of salicylate, the glutamate and adenosine monophosphate anions
      significantly (P < 0.001) inhibited bitterness of the pharmaceuticals more than
      the other anions. Also, there were several specific inhibitory interactions
      between ammonium, sodium and salicylate and certain pharmaceuticals. CONCLUSIONS:
      We conclude that sodium was the most successful cation and glutamate and AMP were
      the most successful anions at inhibiting bitterness. Structure forming and
      breaking properties of ions, as predicted by the Hofmeister series. and other
      physical-chemical ion properties failed to significantly predict bitterness
      inhibition.

PMID- 12180536
TI  - The N-demethylation of the doxepin isomers is mainly catalyzed by the polymorphic
      CYP2C19.
AB  - PURPOSE: This study was conducted to identify the cytochrome P450s (CYPs)
      responsible for the metabolism of the cis- and trans-isomers of the tricyclic
      antidepressant doxepin to its pharmacologically active N-desmethylmetabolite by
      in vitro techniques. METHODS: The doxepin N-demethylation was studied by means of
      pooled human liver microsomes and chemical inhibitors, recombinant human (rh)
      CYPs, and geno- and phenotyped human liver microsomes. RESULTS: The N
      demethylation of both isomers was inhibited most prominently by tranylcypromine
      (CYP2C19) to more than 50%. Furafylline (CYP1A2) and sulfaphenazole (CYP2C9)
      inhibited the N-demethylation to a lesser extent while quinidine (CYP2D6) or
      troleandomycine (CYP3A4) had no effect. Rh-CYP2C19, -CYP1A2, and -CYP2C9 were
      able to N-demethylate cis- and trans-doxepin. Only traces of trans
      desmethyldoxepin were detectable when CYP3A4 was used. The maximum velocity in
      the cis- and transdoxepin N-demethylation was significantly (P < 0.05) lower in
      microsomes with low CYP2C19 activity (345 +/- 44 and 508 +/- 75 pmol/min/ mg
      protein, respectively) compared to those with high CYP2C19 activity (779 +/- 132
      and 1,189 +/- 134 pmollmin/mg). CONCLUSION: The present study demonstrates a
      significant contribution of the polymorphic CYP2C19 to the N-demethylation of
      doxepin. CYP2C9 and CYP1A2 play a minor role and CYP3A4 does not contribute
      substantially.

PMID- 12180537
TI  - Differential modulation of P-glycoprotein expression and activity by non
      nucleoside HIV-1 reverse transcriptase inhibitors in cell culture.
AB  - PURPOSE: This study investigated the effects of the non-nucleoside HIV-1 reverse
      transcriptase inhibitors (NNRTI) nevirapine (NVR), efavirenz (EFV), and
      delavirdine (DLV) on P-glycoprotein (P-gp) activity and expression to anticipate
      P-gp related drug-drug interactions associated with combination therapy. METHODS:
      NNRTIs were evaluated as P-gp substrates by measuring differential transport
      across Caco-2 cell monolayers. Inhibition of P-gp mediated rhodaminel23 (Rh123)
      transport in Caco-2 cells was used to assess P-gp inhibition by NNRTIs. Induction
      of P-gp expression and activity in LS180V cells following 3-day exposure to
      NNRTIs was measured by western blot analysis and cellular Rh123 uptake,
      respectively. RESULTS: The NNRTIs showed no differential transport between the
      basolateral to apical and apical to basolateral direction. NNRTI transport in
      either direction was not affected by the P-gp inhibitor verapamil. DLV inhibited
      Rh123 transport, causing a reduction to 15% of control at 100 microM (IC50 = 30
      microM). NVR caused a concentration-dependent induction of P-gp expression in
      LS180V cells resulting in a 3.5-fold increase in immunoreactive P-gp at 100
      microM NVR. Induction attributable to EFV and DLV was quantitatively smaller. NVR
      significantly reduced cellular uptake of Rh123 into LS180V cells, indicating
      increased drug efflux due to induced P-gp activity; effects of EFV and DLV were
      smaller. Acute DLV treatment of LS180V cells previously induced with NVR or
      ritonavir did not reverse the decreased Rh123 cell accumulation. CONCLUSIONS:
      NNRTIs show differential effects on P-gp activity and expression in vitro.
      Clinical studies are required to elucidate the clinical importance of potential
      drug interactions.

PMID- 12180538
TI  - A novel in vitro delivery system for assessing the biological integrity of
      protein upon release from PLGA microspheres.
AB  - PURPOSE: The development of a novel in vitro system is required to assess the
      stability and release kinetics of a protein microsphere formulation used for drug
      delivery to the brain. METHODS: Microspheres containing lysozyme as model protein
      were prepared using a (w/o/w) emulsion-solvent evaporation process. Both the
      active and total (active + inactive) encapsulation efficiencies and release
      profiles were determined. The biologic activity of lysozyme was measured using
      bacterial cell lysis; total protein content was measured using a 125I-radiolabel.
      A novel in vitro apparatus was developed to determine kinetics over a sustained
      time period (>30 days). RESULTS: The microencapsulation technique allowed an
      entrapment of active lysozyme at 80 +/- 4% and a sustained (>42 days) in vitro
      release. The kinetics study showed that the novel in vitro system was able to
      detect the release of low amounts (ng) of protein. To improve the stability of
      the protein within microspheres and allow the release of biologically active
      lysozyme, a basic additive ( Mg(OH)2 ) was successfully encapsulated.
      CONCLUSIONS: This novel in vitro system was appropriate to study protein
      microsphere release kinetics. In addition, the model is cost-effective and mimes
      brain physiological conditions more closely than previous models.

PMID- 12180539
TI  - Sustained release chemotherapeutic microspheres provide superior efficacy over
      systemic therapy and local bolus infusions.
AB  - PURPOSE: The present studies evaluated the ability of injectable, biodegradable
      microspheres releasing carboplatin, doxorubicin, or 5-fluorouracil to suppress
      the growth of solid tumors implanted subcutaneously or intramuscularly. METHODS:
      Seven to 10 days after implantation of MATB-III cells, rats received systemic
      chemotherapy, intratumoral bolus chemotherapy, or injections of chemotherapeutic
      microspheres into the tumor center or multiple sites along the outer perimeter of
      the tumor. RESULTS: A single treatment with carboplatin, doxorubicin, or 5
      fluorouracil microspheres along the perimeter of the tumors produced a
      significant, dose-related suppression in tumor growth, relative to injections
      directly into the tumor center. Moreover, five temporally-spaced microsphere
      treatments along the tumor perimeter (with either doxorubicin or 5-fluorouracil
      microspheres) completely eradicated 100% of the subcutaneous tumors and 40-53% of
      the intramuscular tumors. Polypharmacy, accomplished by blending doxorubicin- and
      5-fluorouracil-loaded microspheres and injecting them into the tumors was even
      more efficacious than sustained delivery of either drug alone. Comparable doses
      of systemic chemotherapy or intratumoral bolus chemotherapy were ineffective.
      CONCLUSIONS: Injectable microspheres might be ideal for local, sustained delivery
      of chemotherapeutic agents to solid tumors. However, attention must be paid to
      the placement of the microspheres, for injections around the tumor perimeter may
      be required for efficacy.

PMID- 12180541
TI  - Relationship between particle size and impurity incorporation during
      crystallization of (+)-pseudoephedrine hydrochloride, acetaminophen, and adipic
      acid from aqueous solution.

PMID- 12180540
TI  - Long-circulating poly(ethylene glycol)-modified gelatin nanoparticles for
      intracellular delivery.
AB  - PURPOSE: The objective of this study was to develop and characterize long
      circulating, biodegradable, and biocompatible nanoparticulate formulation as an
      intracellular delivery vehicle. METHODS: Poly(ethylene glycol) (PEG)-modified
      gelatin was synthesized by reacting Type-B gelatin with PEG-epoxide. The
      nanoparticles, prepared by pH and temperature controlled ethanol-water solvent
      displacement technique, were characterized for mean size, size distribution, and
      surface morphology. Electron spectroscopy for chemical analysis (ESCA) was used
      to confirm the surface presence of PEG chains. In vitro release of
      tetramethylrhodamine-labeled dextran (TMR-dextran, Mol. wt. 10,000 daltons) from
      the nanoparticle formulations was examined in PBS, with and without 0.2-mg/ml
      protease, at 37 degrees C. Relative cytotoxicity profile of control and PEGylated
      gelatin was evaluated in BT-20 a human breast cancer cell line. The nanoparticles
      were incubated with BT-20 cells to determine uptake and cellular distribution
      using confocal microscopy. RESULTS: Gelatin and PEGylated gelatin nanoparticles
      were found to be spherical in shape with a smooth surface in a size range of 200
      500 nm and a unimodal size distribution. ESCA results showed an increase in the
      ether carbon (-C-O-) peak in the PEGylated gelatin nanoparticles due to the
      presence of PEG chains. The presence of PEG chains decreased the percent release
      of TMR-dextran in the presence of proteolytic enzyme due to steric repulsion.
      Cytotoxicity assays indicated that both gelatin and PEGylated gelatin were
      completely non-toxic to the cells. A large fraction of the administered control
      gelatin and PEGylated gelatin nanoparticles were found to be concentrated in the
      perinuclear region of the BT-20 cells after 12 hours indicating possible
      vesicular transport through initial uptake by endocytosis and endosomal
      processing. CONCLUSION: The results of this study show that PEGylation of gelatin
      may prove beneficial as long-circulating delivery system in vivo. Additionally,
      the nanoparticles could encapsulate hydrophilic macromolecules and are
      internalized by tumor cells.

PMID- 12180542
TI  - Biopharmaceutics classification system: the scientific basis for biowaiver
      extensions.
AB  - The current BSC guidance issued by the FDA allows for biowaivers based on
      conservative criteria. Possible new criteria and class boundaries are proposed
      for additional biowaivers based on the underlying physiology of the
      gastrointestinal tract. The proposed changes in new class boundaries for
      solubility and permeability are as follows: 1. Narrow the required solubility pH
      range from 1.0-7.5 to 1.0-6.8. 2. Reduce the high permeability requirement from
      90% to 85%. The following new criterion and potential biowaiver extension require
      more research: 1. Define a new intermediate permeability class boundary. 2. Allow
      biowaivers for highly soluble and intermediately permeable drugs in IR solid oral
      dosage forms with no less than 85% dissolved in 15 min in all physiologically
      relevant dissolution media, provided these IR products contain only known
      excipients that do not affect the oral drug absorption. The following areas
      require more extensive research: 1. Increase the dose volume for solubility
      classification to 500 mL. 2. Include bile salt in the solubility measurement. 3.
      Use the intrinsic dissolution method for solubility classification. 4. Define an
      intermediate solubility class for BCS Class II drugs. 5. Include surfactants in
      in vitro dissolution testing.

PMID- 12180544
TI  - Cationic cholesterol promotes gene transfection using the nuclear localization
      signal in protamine.
AB  - PURPOSE: The purpose of this study was to evaluate protamine-mediated gene
      transfection by liposomes with a novel cationic cholesterol derivative (I)
      compared to those with DC-Chol or DOTMA (Lipofectin). METHOD: Plasmid pGL3 DNA
      was complexed to the cationic liposomes with the derivative (I), DC-Chol, or
      DOTMA in SFM101(Nissui) at room temperature for 15 min, and thereafter the
      complex was incubated with target cells (NIH3T3) for 4 h at 37 degrees C. The
      cells then were washed and cultured for another 40 h in the growth medium at 37
      degrees C before luciferase assay. RESULTS: The transfection efficiency by the
      liposomes with the derivative (I) was much higher than that by the liposomes with
      DC-Chol or DOTMA. In addition, its transfection efficiency was enhanced greatly
      by the addition of protamine. Atomic force microscopy showed clearly how the size
      of the DNA-liposome complex was changed by protamine. Furthermore, fluorescence
      microscopic images showed that Cy5-labeled antisense DNAs were transferred
      quicker into the nucleus of the target cells by the liposomes with the derivative
      I in the presence of protamine. CONCLUSION: Although there exist several possible
      mechanisms, such as improved protection of DNA intracellularly by derivative (I),
      one possibility is that the DNA-protamine-liposome complex with the derivative
      (I) promoted gene transfection more significantly into the nucleus of the target
      cells using the nuclear localization signal of protamine.

PMID- 12180543
TI  - Rational design of peptide-based tumor vaccines.
AB  - Administration of synthetic peptides derived from proteins uniquely or
      overexpressed in tumor cells (tumor-associated antigens) can elicit tumor
      specific immune responses in vivo. This is because cytotoxic T lymphocytes can
      recognize and lyse tumor cells that display peptides derived from tumor
      associated antigens (TAAs) in the context of class I major histocompatibility
      complex (MHC) molecules. TAA peptides, in contrast to peptides of viral origin,
      generally bind weakly to the MHC molecule. In many cases, this explains the poor
      magnitude of T cell response directed at the tumor in vivo. Improving MHC binding
      as a strategy to upregulate antigen recognition can convert low affinity TAA
      peptides into useful tools in clinical trial settings. High-resolution structures
      of class I MHC molecules reported over the past two decades provided the
      framework for designing peptides that can induce optimal T cell response. This
      review will discuss the basic and clinical aspects of modifying native TAA
      peptides as tumor vaccines.

PMID- 12180545
TI  - Genetic immunization using nanoparticles engineered from microemulsion
      precursors.
AB  - PURPOSE: Genetic immunization using "naked" plasmid DNA (pDNA) has been shown to
      elicit broad humoral and cellular immune responses. However, more versatile and
      perhaps cell-targeted delivery systems are needed. To this end, a novel process
      to engineer cationic nanoparticles coated with pDNA for genetic immunization was
      explored. METHODS; Cationic nanoparticles were engineered from warm oil-in-water
      microemulsion precursors composed of emulsifying wax as the oil phase and
      cetyltrimethylammonium bromide (CTAB) as the cationic surfactant. Plasmid DNA was
      coated on the surface of the cationic nanoparticles to produce pDNA-coated
      nanoparticles. An endosomolytic lipid and/or a dendritic cell-targeting ligand
      (mannan) were incorporated in or deposited on the nanoparticles to enhance the in
      vitro cell transfection efficiency and the in vivo immune responses after
      subcutaneous injection to Balb/C mice. The IgG titer to expressed beta
      galactosidase and the cytokine release from isolated splenocytes after
      stimulation were determined on 28 days. RESULTS: Cationic nanoparticles (around
      100 nm) were engineered within minutes. The pDNA-coated nanoparticles were stable
      at 37 degrees C over 30 min in selected biologic fluids. Transmission electron
      microscopy showed the nanoparticles were spherical. Plasmid DNA-coated
      nanoparticles. especially those with both an endosomolytic lipid and dendritic
      cell-targeting ligand. resulted in significant enhancement in both IgG titer
      (over 16-fold) and T-helper type-1 (Th1-type) cytokine release (up to 300%
      increase) over "naked" pDNA. CONCLUSION: A novel method to engineer pDNA-coated
      nanoparticles for enhanced in vitro cell transfection and enhanced in vivo immune
      responses was reported.

PMID- 12180546
TI  - Bilayer films for mucosal (genetic) immunization via the buccal route in rabbits.
AB  - PURPOSE: The oral buccal mucosa may be an ideal site for mucosal immunization,
      allowing for the needle-free administration of cost-effective vaccines. A novel
      mucoadhesive bilayer film was developed to test the feasibility of this route of
      immunization in rabbits. METHODS: Bilayer films were developed using different
      ratios of Noveon and Eudragit S-100 as the mucoadhesive layer and a
      pharmaceutical wax as the impermeable backing layer. Optimal 3/8-inch films were
      post-loaded with 100 microg of plasmid DNA (CMV-beta-gal) or beta-galactosidase
      protein. The in vitro release rates and stability of the postloaded antigens were
      determined. The films were applied to the buccal pouch of rabbits on days 0. 7,
      and 14, and the humoral and splenocyte proliferative immune responses to beta-gal
      were determined through day 28 and compared to those responses after conventional
      subcutaneous injection of adjuvanted protein. RESULTS: The weight ratio of Noveon
      and Eudragit S-100 had a significant effect on adhesion time of bilayer films.
      Postloaded plasmid DNA and beta-gal remained stable after being released from
      bilayer films (release of -60-80% in 2 h for both). Buccal immunization using
      novel bilayer films (109 +/- 6-microm thickness) containing plasmid DNA led to
      comparable antigen-specific IgG titer to that of subcutaneous protein injection.
      All rabbits immunized with plasmid DNA via the buccal route but none by the
      subcutaneous route with protein antigen demonstrated splenocyte proliferative
      immune responses. CONCLUSION: The feasibility of buccal (genetic) immunization
      with these novel bilayer films was demonstrated.

PMID- 12180547
TI  - Controlled release of plasmid DNA from a genetically engineered silk-elastinlike
      hydrogel.
AB  - PURPOSE: The purpose of this study was to evaluate the potential of a genetically
      engineered silk-elastinlike polymer (SELP) as a matrix for the controlled release
      of plasmid DNA. METHODS: The influences of SELP concentration, DNA concentration,
      SELP cure time, and buffer ionic strength on the release of DNA from SELP
      hydrogels were investigated. To calculate the average effective diffusivity of
      DNA within the hydrogels, the release data were fitted to a known equation.
      RESULTS: DNA was released from SELP hydrogels by an ion-exchange mechanism. Under
      the conditions studied, the release rate was influenced by buffer ionic strength,
      SELP concentration, and SELP cure time but not DNA concentration. The apparent
      diffusivity of pRL-CMV plasmid DNA in SELP hydrogels ranged from 3.78 +/- 0.37 x
      10(-10) cm2/s (for hydrogels containing 12% w/w SELP and cured for 4 h) to 4.69
      +/- 2.81 x 10(-9) cm2/s (for hydrogels containing 8% w/w SELP and cured for 1 h).
      CONCLUSIONS: The ability to precisely customize the structure and physicochemical
      properties of SELPs using recombinant techniques, coupled with their ability to
      form injectable, in situ hydrogel depots that release DNA, renders this class of
      polymers an interesting candidate for further evaluation in controlled gene
      delivery.

PMID- 12180548
TI  - The lower-generation polypropylenimine dendrimers are effective gene-transfer
      agents.
AB  - OBJECTIVE: To evaluate polypropylenimine dendrimers (generations 1-5: DAB 4, DAB
      8, DAB 16, DAB 32, and DAB 64) as gene delivery systems. METHODS: DNA binding was
      evaluated by measuring the reduced fluorescence of ethidium bromide, and
      molecular modelling of dendrimer-DNA complexes also was performed. Cell
      cytotoxicity was evaluated against the A431 cell line using the MTT assay. In
      vitro transfection was evaluated against the A431 cell line using the beta
      galactosidase reporter gene and N-[1-(2,3-dioleoyloxy)propyl]-N,N,N
      trimethylammonium methylsulphate (DOTAP) served as a positive control. RESULTS:
      Molecular modeling and experimental data revealed that DNA binding increased with
      dendrimer generation. Cell cytotoxicity was largely generation dependent, and
      cytotoxicity followed the trend DAB 64 > DAB 32 > DAB 16 > DOTAP > DAB 4 > DAB 8,
      whereas transfection efficacy followed the trend DAB 8 = DOTAP = DAB 16 > DAB 4 >
      DAB 32 = DAB 64. CONCLUSION: The generation 2 polypropylenimine dendrimer
      combines a sufficient level of DNA binding with a low level of cell cytoxicity to
      give it optimum in vitro gene transfer activity.

PMID- 12180550
TI  - Prediction of drug transport through the blood-brain barrier in vivo: a
      comparison between two in vitro cell models.
AB  - PURPOSE: Studies were conducted to evaluate whether the use of an in vitro model
      of the blood-brain barrier (BBB) resulted in more accurate predictions of the in
      vivo transport of compounds compared to the use of a human intestinal cell line
      (Caco-2). METHODS: The in vitro BBB model employs bovine brain capillary
      endothelial cells co-cultured with primary rat astrocytes. The Caco-2 cells
      originate from a human colorectal carcinoma. The rat was used as experimental
      animal for the in vivo studies. RESULTS: Strong correlations (r = 0.93-0.95) were
      found between the results generated by the in vitro model of the BBB and two
      different methodologies to measure the permeability across the BBB in vivo. In
      contrast, a poor correlation (r = 0.68) was obtained between Caco-2 cell data and
      in vivo BBB transport. A relatively poor correlation (r = 0.74) was also found
      between the two in vitro models. CONCLUSION: The present study illustrates the
      limitations of the Caco-2 model to predict BBB permeability of compounds in vivo.
      The results emphasize the fact that the BBB and the intestinal mucosa are two
      fundamentally different biologic barriers, and to be able to make accurate
      predictions about the in vivo CNS penetration of potential drug candidates, it is
      important that the in vitro model possesses the main characteristics of the in
      vivo BBB.

PMID- 12180549
TI  - Glucose-modulated transgene expression via recombinant adeno-associated virus.
AB  - PURPOSE: The objective of this study was to examine glucose modulated reporter
      gene expression via recombinant adeno associated viral vectors both in vitro and
      in vivo. METHODS: Huh7 human hepatoma cells were transduced by recombi nant adeno
      associated virus (rAAV) vectors containing the luciferase gene under control of
      the rat insulin I gene promoter and a cytomegalovirus immediate-early promoter
      driving-enhanced green fluores cence protein gene. The reporter gene expression
      was evaluated by glucose stimulation either in the absence or presence of insulin
      se cretagogues, including phorbol-12-myristate-13-acetate, dibutyryl cy clic AMP,
      and forskolin. In vivo studies were performed by injecting rAAV into the livers
      of streptozotocin-induced diabetic C57BL/6J mice followed by measurements of
      blood glucose concentration and luciferase activity assays 2 weeks after rAAV
      injection. RESULTS: At a multiplicity of infection of 500, approximately 66-69%
      of cells expressed enhanced green fluorescence protein at 48 h post transduction.
      Luciferase activities, driven by the insulin gene promoter, in the rAAV
      transduced hepatoma cells responded to milli molars of glucose. The addition of
      phorbol-12-myristate-13-acetate dibutyryl cyclic AMP, and forskolin increased
      luciferase expression in the presence of either 1 mM or 25 mM glucose. The
      stimulation of luciferase activities by these substances was inhibited by the
      presence of 100 nM staurosporine. Exposure to increments of exogenous in sulin up
      to 10(-7) M inhibited luciferase gene expression in rAAV transduced Huh7 cells.
      The in vivo experiments demonstrated good correlation between luciferase
      activities and blood glucose levels in streptozotocin-induced diabetic animals.
      CONCLUSION: rAAV is a promising vector for hepatic gene therapy for diabetes.
      Glucose and insulin secretagogues modulated transgene ex pression in rAAV
      transduced hepatoma cells, suggesting that condi tions affecting insulin gene
      promoter function in pancreatic islet beta cells also affect transgene expression
      in human hepatoma cells con ferred with insulin gene promoter. Results obtained
      from in viv experiments demonstrated that glucose modulated transgene expres sion
      can be obtained in rAAV-treated diabetic C57BL16J mice.

PMID- 12180551
TI  - Role of ascorbic acid in stratum corneum lipid models exposed to UV irradiation.
AB  - PURPOSE: The effects of ascorbic acid on Stratum corneum lipid models following
      ultraviolet irradiation were studied adding iron ions as transition metal
      catalysts. METHODS: Lipid peroxidation was quantified by the thiobarbituric acid
      assay. The qualitative changes were studied on a molecular level by mass
      spectrometry. To elucidate the nature of free radical involvement we carried out
      electron paramagnetic resonance studies. The influence of ascorbic acid on the
      concentration of hydroxyl radicals was examined using the spin trapping
      technique. Moreover, we checked the vitamin's ability to react with stable
      radicals. RESULTS: Ascorbic acid was found to have prooxidative effects in all
      lipid systems in a concentration dependent manner. The degradation products of
      ascorbic acid after its prooxidative action were detected. The concentration of
      the hydroxyl radicals in the Fenton assay was decreased by ascorbic acid. The
      quantification assay of 2,2-diphenyl-1-picrylhydrazyl hydrate showed reduced
      concentration levels of the stable radical caused by ascorbic acid. CONCLUSIONS:
      Considering human skin and its constant exposure to UV light and oxygen, an
      increased pool of iron ions in irradiated skin and the depletion of co
      antioxidants, the administration of ascorbic acid in cosmetic formulations or in
      sunscreens could unfold adverse effects among the Stratum corneum lipids.

PMID- 12180552
TI  - Transdermal delivery of pergolide from surfactant-based elastic and rigid
      vesicles: characterization and in vitro transport studies.
AB  - PURPOSE: The aim of this study was to investigate the effect of elastic and rigid
      vesicles on the penetration of pergolide across human skin. METHODS: Vesicles
      used consisted of the bilayer-forming surfactant L-595 (sucrose laurate ester)
      and the micelle-forming surfactant PEG-8-L (octaoxyethylene laurate ester),
      together with the stabilizer sulfosuccinate. A series of L-595/PEG-8
      L/sulfosuccinate vesicles were investigated, ranging from very rigid to very
      elastic. Pergolide-loaded elastic and rigid vesicles were visualized using Cryo
      TEM and characterized for size and stability. Transdermal penetration of
      pergolide from different vesicle compositions was studied in vitro using flow
      through Franz diffusion cells. A saturated buffer solution served as the control.
      RESULTS: Vesicle composition had a major effect on the physicochemical
      characteristics, morphology and drug solubility of the vesicular system. L
      595/PEG-8-L/sulfosuccinate (70/30/5) elastic vesicles gave the best balance
      between vesicle stability and elasticity, as well as the highest drug solubility.
      Transport studies clearly showed that elastic vesicles were superior to rigid
      vesicles. Elastic vesicles enhanced the drug transport compared to the buffer
      control, although rigid vesicles decreased the drug transport. The best drug
      transport was achieved from L-595/PEG-8-L/sulfosuccinate (70/30/5) elastic
      vesicles, resulting in a steady-state flux of 13.6 +/- 2.3 ng/ (h*cm2). This was
      a 6.2-fold increase compared to the most rigid vesicles. CONCLUSIONS: This study
      supports the hypothesis that elastic vesicles are superior to rigid vesicles as
      vehicles for transdermal drug delivery.

PMID- 12180553
TI  - Nasal delivery of insulin using novel chitosan based formulations: a comparative
      study in two animal models between simple chitosan formulations and chitosan
      nanoparticles.
AB  - PURPOSE: To investigate whether the widely accepted advantages as sociated with
      the use of chitosan as a nasal drug delivery system might be further improved by
      application of chitosan formulated a nanoparticles. METHODS: Insulin-chitosan
      nanoparticles were prepared by the ionotropic gelation of chitosan glutamate and
      tripolyphosphate pentasodium and by simple complexation of insulin and chitosan.
      The nasal absorption of insulin after administration in chitosan nanoparticle
      formulations and in chitosan solution and powder formulations wa evaluated in
      anaesthetised rats and/or in conscious sheep. RESULTS: Insulin-chitosan
      nanoparticle formulations produced a pharmacological response in the two animal
      models, although in both cases the response in terms of lowering the blood
      glucose levels was less (to 52.9 or 59.7% of basal level in the rat, 72.6% in the
      sheep than that of the nasal insulin chitosan solution formulation (40.1% in the
      rat, 53.0% in the sheep). The insulin-chitosan solution formulation was found to
      be significantly more effective than the complex and nanoparticle formulations.
      The hypoglycaemic response of the rat to the administration of post-loaded
      insulin-chitosan nanopar ticles and insulin-loaded chitosan nanoparticles was
      comparable. As shown in the sheep model, the most effective chitosan formulation
      for nasal insulin absorption was a chitosan powder delivery system with a
      bioavailability of 17.0% as compared to 1.3% and 3.6% for the chitosan
      nanoparticles and chitosan solution formulations, respectively. CONCLUSION: It
      was shown conclusively that chitosan nanoparticles did not improve the absorption
      enhancing effect of chitosan in solution or powder form and that chitosan powder
      was the most effective for mulation for nasal delivery of insulin in the sheep
      model.

PMID- 12180554
TI  - Innovative alcohol- and drug-user treatment of inmates in New Zealand prisons.
AB  - The Kowhai Alcohol and Drug Treatment Unit at Rolleston Prison offers an
      innovative treatment approach for New Zealand inmates. The development of the
      program has involved local staff from Public Prisons, Psychological Services, and
      the Community Probation Service (CPS). This presentation outlines the author's
      impression of this bold innovation. The primary aim of the program is to reduce
      recidivism. This is achieved by assisting inmates to recognize the thoughts,
      emotions, and behaviours that are present in the period preceding and/or during
      the commission of criminal activity--particularly those that are precipitated
      and/or maintained by alcohol and drug use. This insight, coupled with the
      learning of specific coping skills and intensive lifestyle and reintegration
      planning, leads naturally to the follow-up phase that is conducted in the
      community. The functional relationship between offending and substance use is far
      more explicitly addressed in this new program compared with past programs that
      focused more on substance use.

PMID- 12180555
TI  - An outcome evaluation of prison-based treatment programming for substance users.
AB  - This paper briefly documents the results of a broad-based implementation of
      substance user treatment programs within the Federal correctional system in
      Canada.

PMID- 12180556
TI  - A discussion of the concept of technology transfer of research-based drug "abuse"
      prevention and treatment interventions.
AB  - With the availability of both drug user prevention and treatment interventions
      that have demonstrated effectiveness under rigorous experimental design, new
      avenues of research have opened up to bring these strategies to scale. Of major
      importance is adapting evidence-based prevention and treatment programs to
      community specifications without diluting their power. A number of researchers
      have examined this issue from a variety of perspectives. This brief discussion is
      an attempt to bring those perspectives together within a conceptual framework
      that integrates them around research issues and questions. Several theoretical
      perspectives that have not been brought into the technology transfer discussion
      are mentioned, others need to be reviewed for their potential to guide further
      research in this area.

PMID- 12180557
TI  - How do substance "abuse" providers get information to improve treatment?

PMID- 12180558
TI  - A brief overview and introduction to artificial neural networks.
AB  - This article is designed to acquaint professionals working in the field of
      substance use intervention with a range of artificial intelligence nonlinear,
      powerful tools, artificial neural networks, concepts, and paradigms. The family
      of ANNs, when appropriately selected and used, permits the maximization of what
      can be derived from available data as well as our studying and understanding the
      many people, processes, and phenomena which comprise substance use and its
      intervention. The latter represent complex, dynamic, multidimensional phenomena
      which are unpredictable and uncontrollable in the traditional "cause and effect"
      sense. As such they are likely to be nonlinear in their very essence. Using
      linear-based paradigms for planned intervention with nonlinear phenomena brooks
      the all-too-common possibility of using inappropriate intervention paradigms
      and/or drawing misleading conclusions about what is and/or has happened.

PMID- 12180559
TI  - Substitution therapy for heroin addiction.
AB  - Substitution treatment for heroin addiction, defined here as maintenance
      prescribing of opioid agonist drugs to opioid dependent subjects, has increased
      in the last decade. The recent history of substitution treatment in five
      countries--Canada, the U.K., Australia, Israel, and France--is reviewed. In all
      five countries, the critical issues around substitution treatment are similar.
      The first key issue concerns the balance between making treatment accessible and
      attractive, and minimizing diversion to the black market. The second issue
      concerns the role of primary health care in delivering MMT. In general, there has
      been increasing involvement of primary health care, with training and support for
      practitioners. However, there remains uncertainty and official ambivalence over
      whether treatment should be restricted to specialist clinics and practitioners,
      or available through primary care. Most importantly, underlying these issues is
      the problem of stigma being associated with both addiction, and with substitution
      treatment. The underlying problem that treatment is often at odds with community
      values places enormous strains on substitution treatment, and makes the treatment
      system vulnerable to shifting community support and abrupt, politically-driven
      changes in policy.

PMID- 12180560
TI  - Dual diagnosis on "substance abuse".
AB  - Three large U.S. epidemiological surveys researching the prevalence of comorbid
      psychiatric illness and "substance abuse disorders" are reviewed: the
      Epidemiological Catchment Area Study, (N=20,219); the National Comorbidity Survey
      (N=8098), and the National Longitudinal Alcohol Epidemiological Survey
      (N=42,862). Findings suggest that comorbidity is highly prevalent but that
      longitudinal information remains limited limited--which restricts understanding
      of its "natural history," stability, common risk factors, and causal
      relationships.

PMID- 12180561
TI  - Substance user treatment program quality: selected topics.
AB  - This panel explores the "state of the art" in conceptualization and research
      pertinent to program quality in substance user treatment. First, seven critical
      questions for program quality are identified and discussed. Second, a recent
      national evaluation of treatment examines the implications of long-term patient
      outcomes for treatment quality. Third, a large number of clinical trials of
      behavioral and pharmacological treatments for cocaine dependence were conducted
      during the 1990s; this research is synthesized and interpreted. Fourth, progress
      is reported in improving the quality of treatment through standardized criteria
      for patient placement matching.

PMID- 12180562
TI  - Prevention of HIV among drug users.
AB  - The relationship between injection drug use and HIV was established early in the
      HIV epidemic, and injection drug use has continued to be an important risk factor
      for HIV throughout the world. This panel included 4 papers related to HIV
      prevention among drug users, focusing on effective prevention strategies, the
      importance of organizing the AIDS-affected community, the impact of knowledge of
      serostatus on risk behaviors, and developing interventions for drug-using
      homosexual and bisexual men. These papers, addressing various aspects of the
      epidemic and methods to enhance prevention efforts, all indicate that although
      extensive knowledge regarding how to reduce HIV risks among drug users has
      accumulated, many areas for further research and intervention development remain.

PMID- 12180563
TI  - Changing patterns of "drug abuse" in the United States: connecting findings from
      macro- and microepidemiologic studies.
AB  - Trend analyses of the U.S. monitoring data systems (the National Household Survey
      on Drug Abuse and the Monitoring the Future Study) and of the country's
      surveillance program, the Community Epidemiology Work Group (CEWG), indicate that
      several new "drug abuse" patterns have emerged over the past several years. For
      adolescents, drug use rates are converging for females and males, the mean age at
      which youngsters initiate drug use has declined, and more young adolescents are
      reporting using drugs. Furthermore, emergent new drug use patterns are being
      observed by the CEWG. The use of drugs such as Rohypnol, the injecting of crack
      cocaine, and the spread of methamphetamines by new traffickers challenge our
      existing knowledge and understanding of drug use and its prevention. The National
      Institute on Drug Abuse has funded several large longitudinal studies that follow
      selected children and adolescents into their twenties, and some into their
      thirties. This research has been a rich source of information on the determinants
      of initiating and continuing drug abuse. Yet the findings from the surveys have
      not been well explored by the longitudinal studies, nor have the findings from
      the longitudinal studies been used in the surveys to better understand the
      observed changing trends in drug use patterns. This paper addresses six issues
      that have been observed from the findings from analyses of data from the surveys
      or macroepidemiologic studies. Information from the sub-population or micro
      epidemiologic studies are reviewed for possible hypotheses to explain each issue.
      Suggestions for further research and implications for prevention also are
      presented.

PMID- 12180564
TI  - Migration, acculturation, displacement: migratory workers and "substance abuse".
AB  - The following essays represent the topics and issues raised by the panel
      presenters. A diverse group of researchers came together to compare and contrast
      the substance use and "abuse" practices and patterns of marginalized groups in
      their region of the world. The panelists included researchers discussing: the
      hill people of Burma, Maori in New Zealand, Algerians in France, Mexican
      Americans in the United States and predominantly African-American homeless males
      in New York. We found many common themes. In particular, we found that each of
      the marginal populations increased their use of substances with increased time in
      the host society/culture. It was agreed that substance use is not only a process
      of adaptation but also a coping mechanism in, for the most part, hostile and
      unwelcoming environments. We also agreed that "abuse" of substances is not common
      to traditional cultures. Migration to a more modern society was accompanied by
      initiation and/or increase in substance use. When used at all, indigenous people
      tend to use substances in the controlled form of ritual and ceremony. The use of
      substances as a method of desensitizing to day-to-day stressors was adopted with
      exposure to the practises of their new surroundings. We found that there are more
      commonalities in the processes we examined than differences independent of
      location and race/ethnicity.

PMID- 12180565
TI  - Re-enculturation: culturally congruent interventions for Maori with alcohol- and
      drug-use-associated problems in New Zealand.
AB  - Generally, the relationship between culture and substance use has been explored
      in two ways. Firstly, high rates of substance use and related problems amongst
      indigenous and migrant populations generated interest in genetics and cultural
      susceptibility. Acculturation-strain type theories suggested the stress of
      culture-change increased the risk of substance use and related harm. Secondly,
      there has been an increasing emphasis on taking account of the diversity of
      social, psychological, and cultural factors in the assessment and treatment of
      alcohol- and drug-use-associated problems. Utilization of ethnocultural factors
      as a means to promote recovery from alcohol- and drug-use-associated problems is
      a feature of culturally congruent interventions. Maori are the indigenous people
      of New Zealand, and this paper outlines the background to the increasing
      inclusion of customary Maori values, beliefs, and practices in interventions in
      the development of culturally congruent programs.

PMID- 12180566
TI  - Medical outreach to homeless substance users in New York City: preliminary
      results.
AB  - An innovative, experimental, medical out-reach initiative, using a fully-equipped
      mobile medical van with a staff of 2 part-time physicians, a physician assistant,
      a social worker, and a driver/medical aid serving the needs of 1048, mostly male,
      minority group, high-level, homeless New York City substance users with
      infectious diseases is described. The study sample (N = 250) was divided into
      experimental S's who received Intensive case management and a control group who
      could choose to refer themselves to the SW. Biological tests revealed high rates
      of cocaine use and infectious diseases. Preliminary 4-month outcomes (N = 128)
      showed reductions in drug use, homelessness and health complaints in both groups;
      experimental subjects compared with controls received more Public Assistance and
      had fewer emergency room visits.

PMID- 12180567
TI  - Smoking cessation among persons in recovery.
AB  - The literature on smoking cessation for those in recovery from other drug use is
      reviewed. Reasons for engaging in this work, arguments against treatment of
      smoking along with another drug, characteristics of drug users who smoke, and
      treatment content implications are reviewed. Outcomes of 24 studies are
      presented. It is concluded that the future of research and practice in this arena
      should include facilitating smoking cessation among those early in recovery.

PMID- 12180568
TI  - Pathological gambling and substance misuse.
AB  - This paper first discusses the ways in which pathological gambling (a disorder of
      impulse control) and substance misuse are similar. It then examines research
      focusing on substance misuse among pathological gambles, and research on
      pathological gambling among substance misusers, focusing on a study examining
      gambling among 462 methadone patients from New York City. That study found that
      21% of the sample were probable pathological gamblers, while an additional 9%
      were problem gamblers, i.e., they had some problem related to their gambling. The
      treatment implications of these findings and future research directions are also
      discussed.

PMID- 12180570
TI  - Prevention of alcohol and drug "abuse" problems at the community level: what
      research tells us.
AB  - This paper presents alternative models for reducing alcohol-involved problems at
      the local level and a review of research evidence about effectiveness. A computer
      simulation model and results from a community trial in the United States is used
      to illustrate and demonstrate possibilities.

PMID- 12180569
TI  - A critical perspective on cross-cultural contexts for addiction and
      multiculturalism: their meanings and implications in the substance use field.
AB  - Despite evidence of the antiquity and ubiquity of psychoactive substance use,
      much of the literature is devoted to addiction in minority ethnocultural
      subgroups. When researchers study drug use in isolated "primitive" communities,
      they consider drug use to serve as a mechanism of social integration; when they
      study drug use in ethnocultural subgroups in contact with mainstream society,
      they consider drug use as a marker, or sometimes as a cause of social
      disorganization. The implicit assumption appears to be that addiction and race,
      ethnicity, or other minority ethnocultural subgroup membership are linked, and
      more prevalent and/or more problematic in minorities, further problematizing the
      status of minorities. Empirical studies identified through ETOH, the U.S.
      National Institute of Alcohol and Alcoholism (NIAAA)'s Internet-accessible
      computerized database, were subjected to content analysis of their abstracts
      (n(abs) = 44) as well as actual reports (n(rep) = 40). It was found that the
      content of neither abstracts nor actual reports supported the contention that
      there was a greater prevalence of drug use, drug-use-associated problems, or drug
      use-enhancing attitudes in minority ethnocultural subgroups when compared to
      mainstream society (chi2(abs) = 2.16, d.f. = 3, n.s., and chi2(rep) = 3.52, d.f.
      = 2, n.s. respectively). Researchers need to be aware of possible implicit
      assumptions about the relation between ethnicity and addiction.

PMID- 12180571
TI  - The shaman and the rave party: social pharmacology of ecstasy.
AB  - Current psychobiological models of drug addiction are focused on the capability
      of drugs to cause a pathological exploitation of the neural rewarding system.
      This approach has emphasized the role of hedonistic factors in the etiology of
      drug addiction. Comparing primitive and modern settings of intoxication, such as
      shamanic rituals and rave parties, it is possible to confute this assumption. The
      archaic way of perceiving and elaborating drug effects mainly determined their
      use as being for supernatural purposes and excluded recreational purposes. Only
      after a completely profane setting of drug use was developed, did psychoactive
      drugs express all their hedonistic potentialities. This development, however, has
      been a slow process.

PMID- 12180572
TI  - Migration and substance use: evidence from the U.S. National Health Interview
      Survey.
AB  - Representative data from the U.S. National Health Interview Survey are used to
      investigate the substance use patterns of immigrants and compare them to those of
      the native born populations. The information examined is from the 1991
      supplementary Drug and Alcohol Use Data File, which examined the self-reported
      substance use behaviors of approximately 21,000 adults aged 18-44. Findings
      indicate that immigrants to the U.S. in the late twentieth century are less
      likely to use alcohol and other drugs than are native born citizens. Additional
      findings suggest assimilation processes by which exposure to mainstream American
      society leads to patterns of alcohol and illicit drug use among long term
      immigrants that approximates that of the native born population. The patterns of
      substance use observed among immigrants, however, are not consistent with
      acculturative stress mechanisms. These findings provide an important and
      representative profile of the substance use patterns of one of the largest
      international migration streams of the past one hundred years.

PMID- 12180573
TI  - Controlling and policing substance use(rs).
AB  - Controlling drug use--a dynamic, global, politicalized process--is reviewed in
      terms of selected types of drugs, "natural levels" of drug demand and use, drug
      markets and the drug market environment, types of traffickers, illicit drug trade
      profits, approaches to drug control ("War on Drugs", "Zero Tolerance" programs
      and policies, "normalizing" and legalizing selected drugs), including UN's then
      relatively recent "Balanced Approach" and facets of drug law enforcement (drug
      prices and purity levels and values of drug seizures), including various rarely
      noted benefits to intervention programs and control agents. Unresolved issues and
      needed "tools" are noted while considering the implications of the first UN's
      World Drug Report data.

PMID- 12180574
TI  - Drug user treatment within a criminal justice context.
AB  - This paper summarizes what is known, and what is uncertain, about strategies what
      exploit the coercive potential of the criminal justice system to get problem drug
      users to get treatment for their dependency. It considers the links between
      problem drug use and crime, the characteristics of effective treatment for
      problem drug users, the effectiveness of coerced treatment, and the practical
      obstacles in bridging the gap between criminal justice and treatment services. It
      draws on experience in Britain, though it is also informed by the English
      language research literature, especially that carried out in the United States.

PMID- 12180575
TI  - The program of criminal undercover agents sources in the drug trade.
AB  - Information and intelligence have always been, and will remain the most essential
      components of policing, and indeed all law enforcement and security work,
      including the variety of drug control efforts. Sources of information are many
      and varied, ranging from everyday interactions of officers of the law with the
      public, anonymous reports, the use of paid and unpaid informants from the
      criminal underworld, to the law enforcement and security services' use of agents.
      This presentation, based on interviews with "handlers" of informants who are
      offenders and who supply information and evidence against other criminals, who
      may have been his former "comrades" explores: the dilemmas that the informer, and
      the handler face at each stage of the "operation" from recruitment to operation
      in the field, until the agent "fingers" the targets, and becomes a State witness.
      During each stage of the operation the "agents" motivations, fears, sense of
      betrayal (being betrayed and betraying others), being a "snitch", the need to
      protect identity as well as dependency upon the "handler" are the primary issues
      to be considered and resolved. The "handler" may have to tolerate the agent's
      commission of crimes during the operation and often may also have to "treat" the
      informant's spouse. Borrowed identity, which is the main meaning and dynamic of
      the informant's actions, and of any undercover work, will also be analyzed.

PMID- 12180576
TI  - Intravenous induction agents: etomidate.

PMID- 12180577
TI  - Cerebrovascular carbon dioxide reactivity in sheep: effect of propofol or
      isoflurane anaesthesia.
AB  - Propofol and isoflurane are commonly used in neuroanaesthesia. Some published
      data suggest that the use of these agents is associated with impaired cerebral
      blood flow/carbon dioxide (CO2) reactivity. Cerebrovascular CO2 reactivity was
      therefore measured in three cohorts of adult merino sheep: awake (n=6),
      anaesthetized with steady-state propofol (15 mg/min; n=6) and anaesthetized with
      2% isoflurane (n=6). Changes in cerebral blood flow were measured continuously
      from changes in velocities of blood in the sagittal sinus via a Doppler probe.
      Alterations in the partial pressure of carbon dioxide in arterial blood (PaCO2)
      over the range 18-63 mmHg were achieved by altering either the inspired CO2
      concentration or the rate of mechanical ventilation. Cerebral blood flow/CO2
      relationships were determined by linear regression analysis, with changes in
      cerebral blood flow expressed as a percentage of the value for a PaCO2 of 35
      mmHg. Propofol decreased cerebral blood flow by 55% relative to pre-anaesthesia
      values (P=0.0001), while isoflurane did not significantly alter cerebral blood
      flow (88.45% of baseline, P=0.39). Significant linear relationships between
      cerebral blood flow and CO2 tension were determined in all individual studies (r2
      ranged from 0.72 to 0.99). The slopes of the lines were highly variable between
      individuals for the awake cohort (mean 4.73, 1.42-7.12, 95% CI). The slopes for
      the propofol (mean 2.67, 2.06-3.28, 95% CI) and isoflurane (mean 2.82, 219-3.45,
      95% CI) cohorts were more predictable. However, there was no significant
      difference between these anaesthetic agents with respect to the CO2 reactivity of
      cerebral blood flow.

PMID- 12180578
TI  - Pharmacodynamics and atracurium and laudanosine concentrations during a fixed
      continuous infusion of atracurium in mechanically ventilated patients with acute
      respiratory distress syndrome.
AB  - The present study was designed to assess the pharmacodynamics and the plasma
      levels of atracurium and laudanosine found during a 72-hour fixed rate infusion
      of atracurium in acute respiratory distress syndrome patients without renal or
      liver failure. Nine sedated and mechanically ventilated acute respiratory
      distress syndrome patients without renal or liver failure were paralysed with a
      bolus of atracurium (1 mg x kg(-1)) followed by a 72-hour continuous infusion (1
      mg x kg(-1) x h(-1)). The count of train-of-four (TOF) and TOF ratio were
      monitored by an accelerograph until full neuromuscular recovery (T4/T1 > or =
      0.7). Atracurium and laudanosine concentrations were measured from the onset to
      four days after cessation of the infusion. An electroencephalogram was recorded
      daily. Analysis showed that TOF count was always < or = 3 until cessation of the
      infusion. Following cessation, neuromuscular recovery occurred between 31 and 96
      minutes (median value = 45 min). The highest atracurium and laudanosine
      concentrations ranged from 3.3 to 5.8 microg x ml(-1) and from 3 to 20 microg x
      ml(-1) respectively. In four patients with renal impairment, the highest
      laudanosine concentration was > 10 microg x ml(-1). No seizure was recorded. A
      fixed infusion rate of atracurium in acute respiratory distress syndrome patients
      provided an effective muscle paralysis with a rapid neuromuscular recovery but
      can lead to accumulation of laudanosine in patients with renal impairment.

PMID- 12180579
TI  - Effect of preoperative oral use of erythromycin and nizatidine on gastric pH and
      volume.
AB  - This randomized controlled trial examined the effects of preoperative oral
      erythromycin or nizatidine on gastric pH and volume. Sixty patients, ASA 1 and 2
      status scheduled for elective surgery were studied. All subjects received oral
      study medication with 10 ml of water 60 minutes prior to surgery. Patients in
      Group 1 (n=20) were given erythromycin 200 mg, in Group 2 (n=20) nizatidine 300
      mg, and in Group 3 (n=20) placebo capsule. A nasogastric tube was inserted
      immediately after anaesthesia induction. Gastric content was aspirated, and
      volume and pH recorded. pH values determined in Group 1 were 5.6+/-1.87; in Group
      2, 5.65+/-1.92 and in Group 3, 3.5+/-1.93. There was no statistical difference
      between Groups 1 and 2, but there was a statistically significant difference
      between Group 3 and Groups 1 and 2 (P<0.001). The volume of gastric content was
      10.25+/-6.65 ml in Group 1, 10.3+/-6.29 ml in Group 2 and 20.25+/-16.72 ml in
      Group 3. Again, there was no statistical difference between Groups 1 and 2, but
      there was a statistically significant difference between Group 3 and Groups 1 and
      2 (P<0.05). The proportion of patients considered "at risk" of significant lung
      injury should aspiration occur was 10% of Group 1, 5% of Group 2 and 20% of Group
      3 (not statistically different). We conclude that oral erythromycin and
      nizatidine given one hour prior to surgery are effective in reducing gastric pH
      and volume.

PMID- 12180580
TI  - Remifentanil and propofol sedation for retrobulbar nerve block.
AB  - We studied remifentanil and propofol for analgesia and sedation during the
      placement of an ophthalmic block. Eighty ASA I or II patients undergoing elective
      cataract surgery under a retrobulbar block in a rural camp setting were included
      in the study. Patients were randomly divided into four groups and received
      different drug combinations as follows: Group I--remifentanil 1 microg/kg, Group
      II--remifentanil 0.5 microg/kg and propofol 0.5 mg/kg, Group III--remifentanil 1
      microg/kg with propofol 0.5 mg/kg and Group IV--saline 0.1 ml/kg. Patients were
      observed for degree of movement, sedation, pain, recall and respiratory
      depression. No patient in the study groups reported pain or displayed movement
      whereas most of the patients in the control group had significant pain during the
      placement of the block. Also, seven (35%) patients in the control group showed
      significant movement which may have led to failure of block in two patients and
      retrobulbar haemorrhage in one patient. Incidence of significant respiratory
      depression was maximum in Group III patients (60%), followed by Group I (20%) and
      least in Group II (5%). All patients in the study groups remained cooperative and
      obeyed commands except four patients in group III (OAA/S-4). Postoperatively,
      other than the control group, recall was maximum in Group I (55%) and least in
      Group II (5%). Hence, a combination of remifentanil 0.5 microg/kg with propofol
      0.5 mg/kg as a bolus was considered to provide excellent relief of pain and
      anxiety with least adverse effects for the placement of ophthalmic blocks.

PMID- 12180581
TI  - Effect of addition of clonidine to local anaesthetic mixture for peribulbar
      block.
AB  - Clonidine added to local anaesthetics prolongs the duration of anaesthesia and
      analgesia of peripheral, neuraxial and retrobulbar blocks. The present randomized
      blinded controlled study was conducted to evaluate the effect of the addition of
      clonidine to local anaesthetic mixture on the quality, onset time, duration of
      peribulbar block, perioperative analgesia and patients' comfort. The study
      comprised two groups of 12 patients each. Group A (control) patients received 7
      ml of a mixture of 2% lignocaine and hyaluronidase with 1 ml normal saline, while
      group B (clonidine group) patients had clonidine 1 microg/kg added to the above
      mixture. Onset and duration of lid akinesia, globe anaesthesia and akinesia, time
      to first analgesic medication and total analgesic requirement were assessed.
      Patients were monitored for heart rate, blood pressure, sedation and respiratory
      depression. Addition of clonidine to local anaesthetic mixture resulted in a
      significant increase in duration of lid akinesia (85.4+/-25.6 vs 173.3+/-35.3
      min, P<0.001), globe anaesthesia (63.2+/-6.9 vs 78.8+/-17.5 min, P=0.012) and
      globe akinesia (161.3+/-24.3 vs 201.2+/-45.7 min, P=0.016). The onset time and
      quality of block were similar in both the groups. No significant haemodynamic,
      respiratory or sedative effects were recorded. The perioperative pain scores and
      the analgesic requirements were significantly (P<0.01) lower in group B patients.
      We found that addition of clonidine 1 microg/kg to local anaesthetic mixture
      significantly increases the duration of anaesthesia and analgesia after
      peribulbar block.

PMID- 12180582
TI  - Neurolytic celiac plexus block for visceral abdominal malignancy: is prior
      diagnostic block warranted?
AB  - Neurolytic celiac plexus block is a recognised treatment for visceral abdominal
      pain due to malignancy. The need for a diagnostic celiac plexus block prior to
      neurolytic blockade is of questionable value, as it may not predict a positive
      response and may incorrectly predict a lack of response. Our objective is to
      evaluate the efficacy of diagnostic celiac plexus block. The records of 59
      patients treated with celiac plexus block during 1994-2000 were retrospectively
      reviewed. Diagnostic block was performed on 32 patients prior to the decision for
      subsequent neurolytic block (Group 1). Another 27 patients were directly treated
      with a neurolytic celiac plexus block (Group 2). Response of Group 1 to
      diagnostic and neurolytic blocks was compared. Data from Group 2 was used to
      project the response of Group 1 should those patients with negative response to
      diagnostic block proceeded to neurolytic block. A two-by-two table was then
      constructed. The diagnostic celiac plexus block predicted a positive response
      with a sensitivity of 93% and a specificity of 37%. The positive predictive value
      was 85% and the negative predictive value was 58%. The estimated "number needed
      to test" before a "true" nonrespondent to lytic block to be detected was 16.7.
      Therefore, a positive response to diagnostic block correlates positively with
      neurolytic celiac plexus block for abdominal visceral pain due to malignancy.
      However, diagnostic block is a poor predictor when the response is negative.
      Hence, its clinical role is questionable and may not be warranted for patients
      with terminal malignancy.

PMID- 12180583
TI  - Risk factors for epistaxis during nasotracheal intubation.
AB  - We performed a study to confirm which risk factors are significantly associated
      with epistaxis during nasotracheal intubation. One hundred patients who underwent
      nasotracheal intubation were included. Risk factors for epistaxis were analysed
      using the multiple logistic regression analysis with stepwise variable selection
      method. Epistaxis was most likely to occur if transit of the tube through the
      nasal passage was difficult (P=0.0001, odds ratio 625, 95% confidence interval
      3.14-14.26). On the other hand, age and gender, obesity, smoking, tube size,
      repeated attempts of intubation, and intubation performed with the aid of
      Magillforceps were not significantly related with risk of epistaxis. The presence
      of nasal anatomical abnormalities also did not correlate significantly with
      epistaxis. Strategies to ensure smooth transit of the tube through the nasal
      passageways are essential to reduce the incidence of epistaxis.

PMID- 12180585
TI  - The Shikani Seeing Stylet for difficult intubation in children: initial
      experience.
AB  - The Shikani Seeing Stylet is a recently introduced reusable intubating stylet,
      produced in adult and paediatric versions. It combines features of a fibreoptic
      bronchoscope and a lightwand. Inside a malleable stainless steel sheath, the
      Shikani Seeing Stylet has a fibreoptic cable leading to a distal light source and
      high-resolution lens. In use, the stylet is placed in the lumen of the selected
      endotracheal tube and the light source enables the stylet to be used as a
      lightwand, while the fibreoptic capability enables visualization of the laryngeal
      inlet. It is portable, relatively inexpensive and easy to maintain. This report
      describes the use of the stylet on eight occasions in seven children, all of whom
      were assessed preoperatively as being potentially difficult to intubate. Three
      had been difficult to intubate previously. All were anaesthetized using
      inhalational anaesthesia. Once an adequate depth of anaesthesia had been
      achieved, conventional direct laryngoscopy was performed and identified as Grade
      3 in six of the patients and Grade 1 in one. Tracheal intubation was then
      attempted using the Shikani Seeing Stylet. On six of the eight occasions the
      attempt was made by different anaesthetists, none of whom had any prior clinical
      experience with the stylet. There were seven successful intubations and one
      failure in a patient who could not be intubated by any method. The Shikani Seeing
      Stylet seems a useful device for use in children with difficult airway problems,
      suspected cervical spine instability or limited mouth-opening.

PMID- 12180584
TI  - Suspected malignant hyperthermia reactions in New Zealand.
AB  - Early clinical signs, triggering agents, time to onset of reaction, mortality and
      methods of treatment were identified in 123 suspected malignant hyperthermia
      reactions. In vitro contracture test results were compared with clinical signs
      and the Malignant Hyperthermia Clinical Grading Scale. Increased end-tidal carbon
      dioxide is the earliest sign when not preceded by masseter spasm. Earlier
      diagnosis reduces the incidence of rigidity and severe metabolic acidosis. The
      combination of suxamethonium and a potent volatile anaesthetic agent triggers an
      earlier reaction compared with a volatile agent alone. There has been zero
      mortality since 1981, essentially due to a combination of advanced monitoring
      capability, increased anaesthetist awareness of malignant hyperthermia, and
      dantrolene availability. DNA analysis has identified nine New Zealand families
      with ryanodine receptor gene mutations. A positive DNA test indicates malignant
      hyperthermia susceptibility with "causative" mutations but discordance requires
      that negative DNA tests are confirmed with in vitro contracture test. This test
      also demonstrated the shortcomings of the Malignant Hyperthermia Clinical Grading
      Scale.

PMID- 12180586
TI  - Severe pulmonary hypertension in a patient with bronchiectasis complicated by cor
      pulmonale and a right-to-left shunt presenting for surgery.
AB  - A patient with advanced bronchiectasis, severe pulmonary hypertension complicated
      by cor pulmonale and a right-to-left shunt at atrial level presented for sigmoid
      colectomy. We outline the potential perioperative problems of this situation,
      discuss the perioperative risks and describe our clinical approach. A total
      intravenous anaesthetic technique using midazolam, fentanyl, ketamine and
      rocuronium was used to minimize changes in pulmonary and systemic vascular
      resistance and not induce bronchospasm. Preoperative nebulized salbutamol and
      ipratroprium were given to prevent bronchospasm and adrenaline and noradrenaline
      were infused to maintain cardiac output and the balance between systemic and
      pulmonary vascular resistance.

PMID- 12180587
TI  - The effects of inhalation of a novel nitric oxide donor, DETA/NO, in a patient
      with severe hypoxaemia due to acute respiratory distress syndrome.
AB  - Aerosolized NONOates have been investigated in animal models in acute pulmonary
      hypertension, but none have been used in humans. We report the first use of
      aerosolized diethylenetriamine nitric oxide adduct (DETA/NO), a NONOate, in a
      patient with severe acute respiratory distress syndrome. Both pulmonary vascular
      resistance index and mean pulmonary arterial pressure were reduced by a mean of
      26% and 18% respectively after the administration of a single dose of DETA/NO
      (150 micromol). Intrapulmonary shunting also improved. There were no significant
      changes in systemic arterial pressure or arterial methaemoglobin concentration
      after DETA/NO inhalation. We conclude that DETA/NO aerosol produced selective
      pulmonary vasodilation, with an improvement in pulmonary haemodynamics and
      oxygenation, while having no measurable effect on the systemic circulation.

PMID- 12180588
TI  - The use of vasopressin to treat catecholamine-resistant hypotension after
      phaeochromocytoma removal.
AB  - A patient undergoing excision of phaeochromocytoma developed refractory
      hypotension which was complicated by significant intraoperative blood loss.
      Cardiovascular support with fluids, blood and noradrenaline failed to reverse the
      hypotension. Introduction of vasopressin successfully reversed the hypotension.
      The experience with this case suggests that vasopressin may be a useful adjunct
      in the treatment of catecholamine-resistant hypotension after phaeochromocytoma
      excision.

PMID- 12180589
TI  - Anaphylaxis to Haemaccel and cross reactivity to Gelofusin.
AB  - A recent change from Haemaccel to Gelofusin as the preferred colloid for
      resuscitation in our region caused us to review patients who were known to be
      allergic to Haemaccel. As Gelofusin and Haemaccel are both modified gelatine, it
      seemed likely that cross reactivity could occur. Two patients who had been
      diagnosed previously as having had anaphylactic reactions to Haemaccel were
      tested intradermally with dilutions of 1/100 of Haemaccel and Gelofusin. Both
      patients showed similar positive reactions to each agent. It appears that
      patients who are known to be allergic to Haemaccel are probably allergic also to
      Gelofusin. Both patients have been given new Medic Alert bracelets stating
      "Allergic to Haemaccel and Gelofusin".

PMID- 12180590
TI  - Peripartum management of a patient with dopamine beta-hydroxylase deficiency, a
      rare congenital cause of dysautonomia.
AB  - We present the first reported case involving the peripartum anaesthetic
      management of dopamine beta-hydroxylase deficiency in a 22-year-old primigravida
      with high-grade placenta praevia. Elective caesarean section was performed at 36
      weeks gestation with a combined spinal-epidural regional anaesthetic technique.
      Extensive preparation was undertaken to manage the consequences of obstetric
      haemorrhage and consideration given to potential pharmacological sensitivities
      suspected to exist in patients with this rare disorder affecting sympathetic
      nervous system function. An uncomplicated caesarean section was performed from
      which the patient recovered well to be discharged home with a healthy baby.

PMID- 12180591
TI  - Successful use of oral methadone after failure of intravenous morphine and
      ketamine.
AB  - We describe an opioid-tolerant patient with severe acute pain which was
      unrelieved by morphine and ketamine via intravenous patient-controlled analgesia,
      but almost totally relieved by methadone. In the previous 24 hours, 509 mg of
      intravenous morphine and 769 mg of ketamine had been used and this was replaced
      by 200 mg of oral methadone. This implies that the success of methadone in
      morphine tolerant patients chiefly involves factors other than its role as an N
      methyl-D-aspartate receptor antagonist, and that methadone should be considered
      as a replacement for morphine when the N-methyl-D-aspartate antagonist ketamine
      has proved ineffective.

PMID- 12180592
TI  - A painful pulsatile abdominal mass in a young man with elevated blood pressures:
      an unusual presentation of phaeochromocytoma.
AB  - We report an unusual presentation of phaeochromocytoma in a young man with a
      painful, pulsatile abdominal mass and elevated blood pressures. This led to a
      delay in diagnosis and resulted in the administration of triggers of
      catecholamine release, possibly causing a catecholamine surge. This caused the
      development of catecholamine-induced cardiomyopathy and multiple organ failure,
      requiring inotropic and ventilatory support, intra-aortic balloon pump and
      dialysis. Fortunately, his condition reversed with supportive treatment and alpha
      adrenergic blockade. This illustrates the importance of having a high index of
      suspicion of phaeochromocytoma, especially in young patients with elevated blood
      pressures.

PMID- 12180593
TI  - Interscalene brachial plexus block for shoulder surgery in a patient with
      arthrogryposis multiplex congenita.
AB  - A five-year-old child with severe arthrogryposis multiplex congenita and
      malnutrition underwent surgery for chronic osteomyelitis of the head of the left
      humerus. The child had typical features of arthrogryposis multiplex congenita,
      including a difficult airway. Propofol was used for induction and maintenance.
      Spontaneous respiration was maintained with a nasal airway. Analgesia was
      provided with an interscalene brachial plexus block placed using a nerve
      stimulator. No opioid was given. The child had an uneventful recovery with good
      postoperative analgesia. The anaesthetic implications of arthrogryposis multiplex
      congenita are discussed.

PMID- 12180594
TI  - Bilateral vocal cord palsy following interscalene brachial plexus nerve block.
AB  - Acute respiratory complications of an interscalene brachial plexus block include
      ipsilateral phrenic nerve and recurrent laryngeal nerve palsies. A 71-year-old
      woman who had undergone a total thyroidectomy for papillary carcinoma 35 years
      ago was administered a right interscalene brachial plexus block for a shoulder
      hemi-arthroplasty. Subsequently she developed acute respiratory distress
      associated with marked stridor secondary to an acute right vocal cord palsy,
      which was superimposed on what was assumed to be a preexisting left-sided vocal
      cord palsy. On extubation the patient was noted to develop stridor again
      necessitating reintubation and tracheostomy was performed two weeks later. The
      vocal cord palsies failed to resolve over the subsequent 18-month follow-up. We
      describe this case to highlight the significant risk of this procedure in
      patients with preexisting or suspected contralateral vocal cord palsy.

PMID- 12180595
TI  - Spontaneous respiration via an open trachea for resection of a high tracheal
      stenosis in a child.
AB  - The successful management of tracheal stenosis requires compromise between the
      competing interests of the surgical and anaesthetic teams and the resources
      available. A seven-year-old girl with marked tracheal stenosis was successfully
      managed spontaneously breathing via an open trachea and a laryngeal mask.
      Anaesthesia was maintained by propofol infusion. When the trachea was opened,
      supplemental oxygen was administered via a modified cholangiocatheter placed into
      the distal segment. At no point was the trachea intubated.

PMID- 12180596
TI  - Awareness under TIVA: a doctor's personal experience.

PMID- 12180597
TI  - Do anaesthetists need to wear surgical masks in the operating theatre?

PMID- 12180598
TI  - More reports of spinal cord damage by spinal needles.

PMID- 12180599
TI  - Phonomyography--acoustic myography using condenser microphones: a promising new
      method of monitoring neuromuscular transmission.

PMID- 12180601
TI  - Patient Internet use in a community outpatient orthopaedic practice.
AB  - This study evaluated Internet use among orthopaedic patients in a private
      practice general orthopaedic setting. Of 154 respondents, twenty percent had used
      the Internet to research their orthopaedic diagnosis. Search rates were lowest
      for patients with arthritis and highest for patients with disorders of the spine
      or back. Seventy percent of these patients who had searched had found their
      searches helpful, and over 50% of patients who had searched had questions raised
      that they planned to address with their physicians. Of those patients who did
      search the Internet, none reported concern regarding the credibility of Internet
      retrieved material.

PMID- 12180600
TI  - Chondrocyte senescence and telomere regulation: implications in cartilage aging
      and cancer (a brief review).
AB  - Recent studies on osteoarthritis and the cartilage aging in our laboratory
      demonstrate that chronologic age correlates with molecular changes in human
      chondrocytes that affect cell cycle control and replicative life span. These
      findings indicate that age-related changes in chondrocytes may explain the
      heightened risk for development of primary osteoarthritis (OA) with increasing
      age. Concomitant studies of human chondrosarcoma suggest that these aging
      mechanisms may also play a role in preventing the malignant transformation of
      chondrocytes. The convergence at the molecular level of these seemingly
      dissimilar biologic processes provides an excellent opportunity to deepen our
      understanding of the fundamental processes underlying cartilage neoplasia,
      cartilage aging, and osteoarthritis.

PMID- 12180602
TI  - Achilles (the man, the myth, the tendon).

PMID- 12180603
TI  - Biomechanics or necromechanics? Or how to interpret biomechanical studies.
AB  - The field of biomechanics is inextricably linked with orthopaedic surgery: loads
      and load distribution play a major role in the problems we treat and in the
      success and failure of many of our treatments. Nonetheless, despite powerful
      investigational tools, I would argue biomechanics has made a relatively minor
      impact in clinical practice primarily because most studies fail to account for
      the major distinction between living and non-living systems: adaptability. While
      any study requires a clear question or hypothesis or goal, without accounting for
      adaptability and tissue tolerance, these studies might well be termed
      "necromechanical." These studies will always have limited clinical relevance
      unless they contain several key features: 1.) A choice of a mechanical parameter
      which is arguably a surrogate for relevant biological behavior; 2.) A set of
      loading regimens which arguably represent the entire range of loadings
      experienced in vivo; 3.) An explicit discussion of tissue tolerance to the
      mechanical perturbations of the study; 4.) When appropriate (i.e., the question
      relates to longer-term effects), an explicit exploration of tissue adaptation
      over time. Without meeting these requirements, any biomechanical study is suspect
      and requires interpretation with great caution. When meeting these requirements,
      biomechanics can provide powerful tools to explain the function of the body and
      to predict the success or failure of treatments prior to using them on patients.

PMID- 12180604
TI  - The future of academic medicine or is academic medicine to be determined by
      technology?

PMID- 12180605
TI  - Negative pressure dressings for open fracture wounds.

PMID- 12180606
TI  - Autosomal dominant transmission of isolated congenital vertical talus.

PMID- 12180607
TI  - Identification and initial characterization of 6,000 expressed sequenced tags
      (ESTs) from rat normal-growing cartilage and swarm rat chondrosarcoma cDNA
      libraries.
AB  - Chondrosarcoma is the second most common type of skeletal malignancy with a
      survival rate at five years for histological grade III of only 29 percent. The
      development of a reliable chondrosarcoma animal model could enable the study of
      tumor growth and progression, the effect of the host on tumor behavior, and the
      effectiveness of various therapeutic modalities. The Swarm rat chondrosarcoma is
      a tumor tissue line that has been maintained through the years by serial
      subcutaneous injections, and the histochemical characteristics of the tumor have
      remained essentially similar in all transplants over the years. This study was
      designed to initiate the characterization of the Swarm rat chondrosarcoma model
      by gene expression profiling as compared to normal-growing rat cartilage.
      Analysis of the gene expression from both libraries revealed a complex pattern of
      gene expression, including many genes not yet reported to be expressed by
      chondrocytes. It suggests that the biochemical characterization of growing
      cartilage and chondrosarcoma reported to date has only begun to describe the
      complexity of these tissues.

PMID- 12180608
TI  - Adverse reactions to OsteoSet bone graft substitute, the incidence in a
      consecutive series.
AB  - BACKGROUND: The purpose of this study was to identify factors that may be
      associated with the development of a sterile inflammatory reaction to OsteoSet
      (Wright Medical Technology) bone graft substitute. We report on a series of 58
      consecutive cases of patients with benign bone lesions who developed an adverse
      reaction to Osteoset. All procedures were performed by a single orthopaedic
      oncology surgeon. METHODS: Patients who exhibited an adverse reaction to OsteoSet
      and those who did not were analyzed for statistical differences with respect to
      age, sex, volume of graft material used, size of pellet, use of alcohol washes,
      mixing of OsteoSet with allograft, medications, drug allergies, and smoking
      history. Comparisons were made between the reaction group and the non-reaction
      group with respect to the these variables. RESULTS: Eight definite (13.8%) and 3
      probable (5.2%) reactions were identified. Symptoms developed an average of 38.9
      days after the operation. There was no statistically significant difference
      (p>0.05) in the volume of Osteoset used, size of pellet, use of alcohol washes,
      mixing of OsteoSet with allograft, patient age, sex, drug allergies, or smoking
      history. Reported use of at least one medication was statistically significant
      between groups when probable reactions were included with the non-reaction group
      (p < 0.05), but not when probables were analyzed with the definite reaction group
      ( p < 0.10). A review of our patients' medication lists did not reveal any single
      or combination of medications likely to be responsible for this difference. Type
      and location of tumor also did not appear to differ significantly between the two
      groups. CONCLUSIONS: Although we report a 13.8%-19.0% incidence of adverse
      reaction to OsteoSet, we are unable to identify any statistically significant
      factors that might predict the development of a reaction. Fortunately, the
      reaction is essentially self limited and fairly benign requiring only anti
      inflammatories and observation.

PMID- 12180609
TI  - The suppressive effect of hyaluronan on nitric oxide production and cell
      apoptosis in the central region of meniscus following partial meniscectomy.

PMID- 12180610
TI  - Fibular allograft after anterior cervical corpectomy: long term follow-up.
AB  - The purpose of this study was to provide clinical and radiographic evaluation
      after a minimum of two years in patients who had an anterior cervical corpectomy
      and a fibular allograft strut. Nineteen patients returned for a follow-up visit
      which included independent radiographic evaluation as well as completing a Visual
      Analogue Scale and Oswestry and Short-Form 36 questionnaires. The categories of
      fusion were as follows: 1) definitely fused (84%) 2) questionably fused (11%) 3)
      definitely not fused (5%). The average VAS was 29 mm (range 0-85). The Oswestry
      Back Scores showed relatively low levels of significant pain with an average
      score of 29 (range 0-73). Anterior cervical corpectomy followed by an allograft
      fibular strut provides for relatively high rates of arthrodesis without severe
      loss of height or sagittal alignment at long term radiographic follow-up.

PMID- 12180612
TI  - Relapsing clubfoot: causes, prevention, and treatment.

PMID- 12180613
TI  - A retrospective review of congenital pseudarthrosis of the tibia.
AB  - Thirty-three children with congenital pseudarthrosis of the tibia seen from 1970
      to 1997 at the Shriners Hospitals for Children in Lexington, KY were
      retrospectively reviewed. Twelve children were excluded due to follow-up of less
      than 2 years. Data was collected on age, sex, side and associated
      neurofibromatosis from the medical records of the remaining 21 children. Lesions
      were classified as to status at birth. The number of surgical attempts for union
      was recorded. Presence of bony union, deformity, and limb length discrepancy was
      noted. The mean age at last follow-up was 13 years. Union was reported in 10
      children (48%). There was no union after more than 3 surgical attempts. The 11
      children without union had an average of 4 surgical attempts (range 2-6).
      Amputation was performed in 7 of the 11 children without union. No predictor for
      nonunion was identified. Amputation was frequently needed.

PMID- 12180611
TI  - Expression of CD44 in human neoplastic and normal hyaline cartilage.
AB  - Although low-grade cartilage neoplasms typically consist of hyaline-like
      cartilage, most of them also contain some fibrocartilaginous regions. CD44, a
      cell surface receptor for hyaluronan, has been identified in cartilage. A family
      of alternatively spliced mRNA containing the variant 6 (v6) exon sequence of CD44
      has been linked to several types of neoplasms. We hypothesized that expressions
      of v6-containing CD44 species are associated with fibrocartilaginous regions of
      low-grade cartilage neoplasms. To test this hypothesis we performed reverse
      transcriptase-polymerase chain reaction (RT-PCR) and immunohistochemical analysis
      on eight samples: four from normal articular cartilage, one from a synovial
      chondromatosis, and three chondrosarcomas which were graded as I and I/II. The
      standard CD44s and a unique v6-containing CD44 species (CD44v6-10) were
      identified in all tissue samples by RT-PCR analysis. Immunohistochemically, using
      an antibody that cross-reacted with all CD44 species, CD44 was localized to the
      cell surface, lacuna wall and intracellular compartment of the chondrocytes in
      the middle and deep zone of normal cartilage, as well as with cells throughout
      the neoplastic masses. Utilizing an antibody specific for v6-containing CD44
      species, the variant species was identified throughout cells of the middle and
      deep zone of normal cartilage, and localized selectively to intracellular
      positions. In neoplastic masses, v6-containing CD44 species were found associated
      only with cells in the hyaline-like cartilage, but not in the fibrocartilaginous
      regions. Thus a differential expression of the v6-containing CD44 species in the
      neoplastic masses containing both hyaline-like cartilage and fibrocartilaginous
      regions was observed when compared to its homogenous expression in normal hyaline
      cartilage. An involvement between the lack of the variant CD44 (v6-containing)
      and altered tissue phenotype (e.g., fibrocartilaginous) is suggested.

PMID- 12180614
TI  - Painful spastic hip dislocation: proximal femoral resection.
AB  - The dislocated hip in a non-ambulatory child with spastic paresis tends to be a
      painful interference to sleep, sitting upright, and perineal care. Proximal
      femoral resection-interposition arthroplasty is one method of treatment for this
      condition. We reviewed eight hips, two bilateral cases, with a mean follow-up of
      30 months. Clinical improvement was observed in all except one case, with respect
      to pain relief and sitting tolerance. Some proximal migration was observed in
      three cases, despite routine post-operative skeletal traction in all cases and
      careful soft tissue interposition. One case showed significant heterotopic
      ossification which restricted prolonged sitting. This patient needed some
      occasional medication for pain.

PMID- 12180615
TI  - Observations on the development of the acetabulum following Chiari osteotomy.
AB  - A detailed analysis of acetabular development following Chiari osteotomy in ten
      patients with neuromuscular disease revealed an anti-Chiari effect in only one
      patient.

PMID- 12180616
TI  - Low-grade/dedifferentiated/high-grade chondrosarcoma: a case of histological and
      biological progression.

PMID- 12180619
TI  - Osteochondrosis of the superior pole of the patella: two cases with histologic
      correlation.
AB  - Two cases of osteochondrosis of the superior pole of the patella are reported
      with histologic findings. Both patients were young girls; one had mild cerebral
      palsy. Sixteen cases of this disorder have been documented but without histologic
      study. The histologic features of these two cases showed osteonecrosis with
      reparative changes. These findings support that this entity is similar to other
      osteochondroses of the quadriceps mechanism: Osgood-Schlatter disease and Sinding
      Larsen-Johansson disease.

PMID- 12180618
TI  - Idiopathic brachial neuritis.
AB  - Idiopathic brachial neuritis is a well defined clinical condition that most
      commonly affects young adults, seen usually by primary care physicians,
      neurologists or orthopaedic surgeons. Its onset is characterized by acute, aching
      shoulder pain lasting a few days to weeks, followed by progressive shoulder
      girdle and upper extremity weakness and atrophy, with a slow but progressive
      recovery of motor function over 6 to 18 months. Its early recognition can help
      avoid unnecessary and potentially harmful diagnostic and therapeutic
      interventions, and avoid delays in prescribing appropriate therapies that may be
      helpful only early in the course of the disease. We present a case of idiopathic
      brachial neuritis and discuss important aspects of the disease and difficulties
      in reaching the correct diagnosis.

PMID- 12180617
TI  - Minimum ten-year follow-up of cemented total hip replacement in patients with
      osteonecrosis of the femoral head.
AB  - Between November 1970 and September 1984 the senior author performed fifty-three
      consecutive total hip arthroplasties with cement in forty-one patients with the
      diagnosis of osteonecrosis of the femoral head. Five hips in three patients with
      failed renal transplants requiring chronic hemodialysis were excluded. At the
      time of final review, a minimum of ten years after the procedure, twenty-one
      patients (twenty-eight hips) were living, fifteen patients (eighteen hips) had
      died, and two patients (two hips) were lost to follow-up. A minimum ten-year
      follow-up radiograph was obtained on twenty-two (79%) of the hips in surviving
      patients. During the follow-up period 17.4% of hips (eight hips) required
      revision: 13.0% (six hips) for aseptic loosening, 2.2% (one hip) for sepsis, and
      2.2% (one hip) for recurrent dislocation. All eight revisions occurred in
      patients living at time of final review, giving a revision prevalence of 22.9%
      (17.1% for aseptic loosening, 2.9% for sepsis, and 2.9% for recurrent
      dislocation) in patients surviving ten years. The prevalence of revision of the
      femoral component for aseptic loosening was 6.5% (three hips) for all hips and
      9.1% (three hips) in patients surviving at least ten years. The prevalence of
      femoral aseptic loosening, defined as those components revised for aseptic
      loosening and those that demonstrated definite or probable radiographic
      loosening, was 13.0% (six hips) for all hips and 28.6% (six hips) for hips with
      at least ten-year radiographic follow-up. The prevalence of revision of the
      acetabular component for aseptic loosening was 13.0% (six hips) for all hips and
      18.2% (six hips) in patients surviving at least ten years. The prevalence of
      acetabular aseptic loosening was 15.2% (seven hips) for all hips and 29.2% (seven
      hips) for hips with at least ten-year radiographic follow-up. In patients with
      osteonecrosis of the femoral head survivorship was significantly inferior to that
      in the senior author's overall patient population with regard to revision for
      aseptic loosening (p=0.019), revision for acetabular loosening (p=0.01), revision
      for femoral loosening (p=0.008), and aseptic femoral loosening (p=0.004).
      Survivorship to aseptic acetabular loosening was not significantly different
      (p=0.32). Young age at the time of surgery significantly increased the risk of
      subsequent component loosening (p<0.008) and revision due to aseptic loosening
      (p<0.002). These findings demonstrate the relatively poor durability of cemented
      total hip arthroplasty in patients with osteonecrosis of the femoral head as
      compared to patients with other diagnoses and suggest that the younger age in
      this patient population compromises results.

PMID- 12180620
TI  - Resistance to activated protein C and digital thrombosis.
AB  - Resistance to activated protein C is a newly described genetic coagulation
      disorder previously only reported in patients with venous thromboembolism or
      central arterial embolism (cerebral or coronary). We report this defect in
      association with digital artery thrombosis and describe the pathophysiology of
      this disorder.

PMID- 12180622
TI  - Forty-year outcome of ankle "cup" arthroplasty for post-traumatic arthritis.
AB  - Ankle arthroplasty for post-traumatic tibiotalar arthritis remains controversial.
      The current literature strongly recommends arthrodesis, especially in those
      patients who will overload the joint: the young, the active and the overweight
      patients. The case described here is a 40-year follow up. A 31-year old man
      underwent talar dome resurfacing with a custom Vitallium implant for post
      traumatic arthritis in 1962. He continued to work as a heavy laborer until
      retirement in 1987 and presently remains virtually asymptomatic with regard to
      his foot and ankle. The longevity of this individual implant has been remarkable.
      The unique design, minimal resection, surgical approach and remarkable success
      merit discussion in the light of publication of predominantly bleak reports of
      arthroplasty in this patient population.

PMID- 12180621
TI  - Dramatic subperiosteal bone formation following physeal injury in patients with
      myelomeningocele.
AB  - We present five cases of dramatic subperiosteal bone formation following fracture
      of the distal femoral physis in children with myelomeningocele. These fractures
      often go unrecognized due to lack of displacement and/or pain. Children present
      with a swollen, warm extremity and often systemic signs of inflammation, but
      rarely any pain or history of trauma. The dramatic radiographic appearance can
      cause a diagnostic dilemma. We present these cases in order to familiarize the
      clinician with the oftentimes dramatic appearance of this injury.

PMID- 12180623
TI  - Obligations.

PMID- 12180625
TI  - Effect of CounterForce brace on symptomatic relief in a group of patients with
      symptomatic unicompartmental osteoarthritis: a prospective 2-year investigation.
AB  - We investigated the effect of the CounterForce brace (Breg, Inc, Vista, Calif) on
      symptomatic relief in a group of 30 patients who had symptomatic unicompartmental
      osteoarthritis and who had undergone at least 6 months of conservative treatment
      without resolution of symptoms. After 8 weeks of brace use, the majority of
      patients reported statistically significant improvements-substantial reduction in
      pain, increase in ability to work and to engage in activities of daily living,
      and substantial reduction in use of oral pain medication. At long-term follow-up
      (mean, 2.7 years), 41% of 29 patients were still using the brace, 35% had stopped
      using the brace (for a variety of reasons), and 24% had undergone arthroplasty.

PMID- 12180624
TI  - The etiology of adolescent idiopathic scoliosis.
AB  - The etiology of adolescent idiopathic scoliosis (AIS), the most common form of
      scoliosis, is unclear. Researchers with divergent perspectives have tried to
      better define this etiology. Genetics, growth hormone secretion, connective
      tissue structure, muscle structure, vestibular dysfunction, melatonin secretion,
      and platelet microstructure are major areas of focus. In this article, we review
      the literature in these areas and present the consensus on proposed hypotheses.
      Studies that simplify the etiology to a single factor have been inconclusive or
      unsuccessful. Most likely, the etiology is multifactorial, and reported
      associations are links in pathogenesis rather than etiologic factors. Research is
      needed to better define the role of all factors in AIS development.

PMID- 12180626
TI  - Effects of trunk position on back surface-contour measured by raster
      stereophotography.
AB  - A study of the contour of the surface of the back was conducted using the Quantec
      spinal image system (QSIS; raster stereophotography) and the Vicon 3-dimensional
      (3-D) motion analysis system with a plaster model of the scoliotic spine. With
      postural changes in 3 dimensions came alterations in the surface shape of the
      back. Most changes in QSIS parameters occurred in the coronal plane. The study
      showed that model 1, with 9 degrees of Q angle (similar to Cobb angle in the
      coronal plane) in right thoracolumbar scoliosis, altered 3-D metrics less than
      model 2 did, with 54 degrees of Q angle in scoliosis. The change in the position
      of the trunk in the transverse plane had a more significant impact on the QSIS
      parameters. Raster stereophotography has been used clinically to monitor curve
      progression. Changes in transverse rotation of the trunk correlate significantly
      with variations in Q angle and axial rotation. Clinicians using a raster
      stereophotograph system to assess scoliotic deformity need to control postural
      sway, as doing so results in more stable and reproducible measurements that can
      be used for clinical follow-up.

PMID- 12180627
TI  - Percutaneous pin fixation of a femoral neck fracture complicated by deep
      infection in a 12-year-old boy.
AB  - Avascular necrosis with or without resultant limb-length discrepancy and problems
      with bony union is not uncommon after femoral neck fractures in the pediatric
      population. This rare case of infection after closed reduction and percutaneous
      pinning of an intracapsular fracture of the hip in a child illustrates the
      treatment difficulties posed by joint sepsis and the value of modern scanning
      techniques.

PMID- 12180628
TI  - Intraosseous lipoma of the proximal radius with extraosseous extension and a
      secondary posterior interosseous nerve palsy.
AB  - We describe an unusual and previously unreported case of a histologically
      verified solitary intraosseous lipoma of the proximal radius with extraosseous
      tumor extension and a secondary posterior interosseous nerve palsy. A successful
      outcome was achieved after intralesional resection of the soft-tissue tumor
      extension, curettage of the proximal radius, autogenous cancellous bone grafting
      of the resultant intramedullary defect, and tendon transfers.

PMID- 12180629
TI  - Dysphagia caused by anterior cervical osteophytes: a case report.
AB  - This 79-year-old man had a several-year history of dysphagia. On presentation, he
      spoke with difficulty but was not short of breath, and hemoptysis was present. A
      17-mm osteophyte anterior to C3-C4 encroached on the posterior aspect of the oral
      pharynx and esophagus. The patient underwent C3-C6 anterior ostectomy; recovery
      was complete within 4 weeks.

PMID- 12180630
TI  - Effect of displacement of ulna-shaft fractures on forearm rotation: a cadaveric
      model.
AB  - Nonoperative treatment of ulna-shaft fractures may result in healing with
      residual displacement. In the study reported here, we used a cadaveric model to
      try to determine whether displacement significantly reduces forearm supination
      and pronation. Transverse osteotomies were made one third, one half, and two
      thirds of the distance from the proximal end to the distal end of each of 7 fresh
      cadaveric forearms. Displacements of 50% and 100% were tested at each osteotomy
      site. Specimens were mounted on a material-testing machine, and forearm rotation
      was determined. Supination loss was less than 15 degrees for all directions of
      displacement at all osteotomy sites. Pronation loss was less than 10 degrees at
      the distal osteotomy site; at the middle osteotomy site, pronation loss was 19
      degrees with 100% radial displacement (P < .05) and 20 degrees with 100% ulnar
      displacement (P< .05); and, at the proximal osteotomy site, pronation loss was 19
      degrees with 50% radial displacement (P < .01), 41 degrees with 100% radial
      displacement (P < .0005), and 33 degrees with 100% ulnar displacement (P < .005).
      We conclude that large residual displacement in distal fractures and moderate
      residual displacement in midshaft fractures do not significantly compromise
      forearm rotation. Proximal displacement was less tolerated in this model and
      resulted in significantly reduced forearm rotation.

PMID- 12180631
TI  - Technique for fabrication of an antibiotic-loaded cement hemiarthroplasty
      (ANTILOCH) prosthesis for infected total hip arthroplasty.
AB  - In North America, staged reimplantation is the preferred treatment for infected
      total hip arthroplasty. A simple technique for implantation of an antibiotic
      loaded cement spacer molded in the shape of a hemiarthroplasty prosthesis is
      described. A Teflon mold was cast in the shape of an Austin Moore hip
      hemiarthroplasty prosthesis. This mold allows for fabrication of a solid
      antibiotic-loaded cement spacer that accurately reproduces the shape of a
      hemiarthroplasty prosthesis. This technique allows for easy insertion, patient
      comfort, between-stage mobility, and local concentric delivery of antibiotic.

PMID- 12180632
TI  - Collapsing glomerulopathy--a new pattern of renal injury.
AB  - Collapsing glomerulopathy is a pattern of renal injury that has emerged along
      with the epidemic of HIV infection. The disease process is now increasingly
      recognized in non-HIV patients. In HIV and non-HIV patients the disease shares
      many clinical and pathologic features, and, we presume, pathogenetic factors. The
      disease entity is characterized by very heavy proteinuria frequently combined
      with rapidly progressive renal failure, poor outcome, glomerular collapse with
      hyperplasia and other degenerative changes of the visceral epithelial cells, and
      prominent tubulointerstitial injury with frequent microcystic changes. HIV
      associated nephropathy has a higher prevalence in blacks, high frequency of intra
      endothelial tubuloreticular inclusions, and prominent microcystic tubular
      changes. These differences, however, are not sufficient to predict the patient's
      HIV status from the biopsy findings alone. Collapsing glomerulopathy can also
      develop in association with lymphoproliferative disorders, systemic lupus
      erythematosus-like and other autoimmune diseases, other immune deficiency
      syndromes and viral infections, and in the context of immunosuppressive therapy.

PMID- 12180634
TI  - Renal biopsy interpretation in Alport Syndrome.
AB  - Alport Syndrome is a heritable progressive renal disease that, despite the large
      number of published studies, because of its genetic, clinical,
      immunohistochemical, and ultrastructural heterogeneity, still remains a
      diagnostic challenge. The focus of the discussion is on electron microscopy and
      immunohistochemistry Col (IV) chains. The differential diagnosis from thin
      glomerular basement membrane disease is discussed in depth, because both are
      familial, and can have similar clinical presentation and even ultrastructural
      pathology, but with a different outcome. The diagnostic role of molecular
      genetics, which identified the presence of collagen IV gene mutations and its
      relationship to the phenotypic expression of the renal damage, is also discussed.

PMID- 12180633
TI  - Glomerulopathies with organized deposits.
AB  - Glomerulopathies with organized deposits are much less frequent than those with
      usual-type immune complex deposits, even in busy renal biopsy practices. It is
      important to be able to provide the correct diagnosis because of the therapeutic
      and prognostic implications that may follow. This goal is achieved by thoughtful
      consideration of all pathologic and clinical findings. This review presents the
      salient features of amyloidosis, cryoglobulinemic glomerulonephritis, fibrillary
      glomerulonephritis, immunotactoid glomerulopathy, collagenofibrotic
      glomerulopathy, and fibronectin glomerulopathy. We also point out matrical
      fibrillary deposits that may mimic some of the above entities at the
      ultrastructural level. Emphasis is placed, through comparative illustrations, on
      the prominent role of electron microscopy.

PMID- 12180635
TI  - Diagnostic dilemmas in atypical postinfectious glomerulonephritis.
AB  - This study discusses the differential diagnosis of atypical postinfectious
      glomerulonephritis (PIGN) which may mimic a great variety of glomerular diseases.
      These include mild mesangial and/or endocapillary glomerulonephritis (GN) focal
      segmental glomerulosclerosis (FSGS) with diffuse IgM mesangial deposits,
      crescentic GN with C3 hump-like deposits, focal mesangiocapillary GN superimposed
      on endocapillary pattern, membranous GN with diffuse exudative changes,
      crescentic GN with microabscesses, and postinfectious glomerulonephritis with
      anti-GBM linear deposits.

PMID- 12180636
TI  - Diabetic glomerulopathy: unusual patterns and dual disease.
AB  - Diabetic glomerulopathy is a well-recognized consequence of both type I and type
      II diabetes. Occasionally, pathologic diagnosis may be challenging for the
      pathologist. These circumstances include atypical light microscopy or diabetic
      change with a second superimposed glomerulopathy (dual disease). We have compiled
      a selection of 12 renal biopsies from diabetic patients that show either an
      unusual pattern of nephropathy or "dual disease," as well as 2 cases in which the
      patient had no history of diabetes but had renal biopsies exhibiting changes
      consistent with diabetic nephropathy. The salient diagnostic features are
      discussed. To accurately assess these biopsies, immunofluorescence and electron
      microscopy become essential, and a broadened differential diagnosis must be
      considered.

PMID- 12180637
TI  - Glomerular injury associated with hepatitis C infection: a correlation with blood
      and tissue HCV-PCR.
AB  - Membranoproliferative glomerulonephritis, with or without cryoglobulinemia, and
      membranous glomerulonephritis are the best characterized glomerulonephropathies
      associated with hepatitis C virus (HCV) infection. Other more unusual patterns of
      glomerular injury, including IgA nephropathy, focal segmental glomerulosclerosis,
      crescentic glomerulonephritis, fibrillary glomerulonephritis, immunotactoid
      glomerulopathy, and thrombotic microangiopathy, have also been associated with
      HCV infection, but primarily on an anecdotal basis. It remains uncertain whether
      the patterns of glomerular injury seen in HCV infected patients, particularly the
      unusual patterns, represent a disease process specifically related to HCV
      infection or whether they represent nonspecific patterns of injury due to other
      causes that happen to occur in HCV-infected patients. We examine this issue by
      reviewing the epidemiological and pathological evidence in the literature that
      either supports or refutes a specific relationship between HCV and the pattern of
      glomerular injury. We also include our experience with 31 HCV-infected patients.
      In addition, the pathogenesis of HCV-associated glomerulonephropathies is
      discussed with an emphasis on the significance of detecting HCV in renal biopsies
      by reverse transcriptase-polymerase chain reaction.

PMID- 12180638
TI  - The complexity of multiple variables.

PMID- 12180640
TI  - Defining resident abuse within the culture of long-term care institutions.
AB  - Although researchers have identified the presence of resident abuse within long
      term carefacilities, it has not come under the same scrutiny as have other
      aspects of abuse against older adults. This is due, in part, to the difficulty in
      defining the phenomenon. The purpose of this study was to articulate a definition
      of resident abuse as perceived by registered nurses working in long-term care
      institutions. Ethnoscience was the method used to answer this question. The five
      categories of resident abuse characteristics--perception of hurtfelt by older
      residents, acts of omission or commission, context of care, intentional or
      unintentional, and behavioral clusters--that emerged through semistructured
      interviews and focus groups reflect the descriptions given by participants.
      Identifying a common definition of resident abuse suggests that assessment and
      intervention to reduce episodes of it are more likely to be effective.

PMID- 12180639
TI  - Falling short of the mark: tales of life after hospital discharge.
AB  - The purpose of this qualitative study was to explore the everyday issues,
      challenges, struggles, and needs of elderly, community-dwelling women in the
      first weeks posthospital discharge. Fourteen elderly women were interviewed in
      their homes 6 to 8 weeksfollowing hospitalization. In addition, using a process
      based on photo novella or photovoice, 4 of the women took photographs of their
      everyday lives. The photos were used as triggers during the interviews. The
      interviews were analyzed to identify the themes of the women's experiences. The
      overarching theme was that hospital discharge plans "fall short of the mark"
      because theyfailed to reflect the complexity of the posthospitalization
      experience by focusing primarily on very basic physical and medically related
      needs rather than on the reality of the women's recovery. These findings are
      alarming given the aging population. The implications for hospital discharge
      planners, home care service providers, and policy decision makers are discussed.

PMID- 12180641
TI  - Leave-taking experiences in the lives of abused women.
AB  - The World Health Organization identifies domestic violence as a major health
      crisis confronting women across the globe. The addition of women's voices about
      their abusive experiences increases understandings of domestic violence. In this
      phenomenological investigation of the coping strategies of abused women, 17 women
      provided meaningful insights into how, why, and when they left abusive
      relationships. Timing, selection of support systems, and intuition add new
      descriptions about abused women's leave-taking experiences. Implications for
      nursing practice include the use of helpful questioning and employment of the
      advocacy role. Based on thefindings of this study, more research is called for
      that allows abused women to demonstrate the variety of their experiences with the
      leave-taking process.

PMID- 12180642
TI  - Alternative theories of happiness in early adolescents.
AB  - The purpose of this study was to examine a set of variables representing enabling
      mechanisms vis-a-vis a set of variables representing personality characteristics
      in relation to happiness in early adolescents: these two theoretical perspectives
      were assessed using hierarchical analyses of sets that determined which of the
      two has greater explanatory power in relation to happiness. The final sample
      consisted of 127 early adolescents, ages 12 to 14, who responded to instruments
      measuring happiness, self-esteem, future time perspective, optimism, vigor,
      change, and social support in classrooms. Using hierarchical analyses of sets,
      the results indicated that the enabling mechanisms set explained more variance in
      happiness when entered first (65%) or second (22%) than did the personality
      characteristics set when entered first (50%) or second (7%) in the analyses.
      Implicationsfor nursing are addressed.

PMID- 12180643
TI  - A case study of comorbidities: vocal cord dysfunction, asthma, and panic
      disorder.
AB  - The purpose of this case study was to describe the nature of the symptom episodes
      experienced by a 24-year-old woman diagnosed with VCD, asthma, and panic
      disorder. A multiple card sort procedure was used to identify the type, order of
      presentation, and severity of symptoms experienced by the participant during her
      typical symptom episodes. Seven types of symptom episodes were investigated
      including VCD, asthma, and panic episodes; and co-occurring or combined episodes
      of VCD and asthma; VCD and panic; asthma and panic; and VCD, asthma, and panic.
      The variability and complexity of the participant's symptom episodes, which are
      described, led to the development of a new VCD/asthma/panic comorbidities symptom
      classification system.

PMID- 12180644
TI  - The minimum data set: predicting malnutrition in newly admitted nursing home
      residents.
AB  - The purpose of this study was to describe the prevalence of protein-calorie
      malnutrition (PCM) among newly admitted elderly nursing home residents and
      identify the most significant predictors of PCM using Minimum Data Set (MDS)
      variables. Using a cross-sectional design, the authors studied 306 nursing home
      residents. Malnutrition risk factors found on the MDS were measured for each
      resident. Overall, 118 (38.6%) residents met the Nutrition Screening Initiative
      Guidelines for PCM. MDS variables found to be significant predictors were weight
      loss, leaves 25% or more offood uneaten at most meals, psychiatric/mood
      diagnoses, deteriorated ability to participate in activities of daily living. and
      older age. Three additional variables (antidepressant use, diuretic use,
      therapeutic diet) were found to be protective-residents with these variables were
      more likely to have a normal body mass index. MDS data provide an opportunity for
      early identification of residents who are at riskfor PCM and accompanying
      morbidity.

PMID- 12180645
TI  - In search of authentic inhibitors of HIV-1 integration.
AB  - Current strategies for the treatment of HIV infection are based on cocktails of
      drugs that target the viral reverse transcriptase or protease enzymes. At
      present, the clinical benefit of this combination therapy for HIV-infected
      patients is considerable, although it is not clear how long this effect will last
      taking into account the emergence of multiple drug-resistant viral strains.
      Addition of new anti-HIV drugs targeting additional steps of the viral
      replication cycle may increase the potency of inhibition and prevent resistance
      development. During HIV replication, integration of the viral genome into the
      cellular chromosome is an essential step catalysed by the viral integrase.
      Although HIV integrase is an attractive target for antiviral therapy, so far all
      research efforts have led to the identification of only one series of compounds
      that selectively inhibit the integration step during HIV replication, namely the
      diketo acids. In this review we try to address the question why it has proven so
      difficult to find potent and selective integrase inhibitors. We point to
      potential pitfalls in defining an inhibitor as an authentic integrase inhibitor,
      and propose new strategies and technologies for the discovery of authentic HIV
      integration inhibitors.

PMID- 12180647
TI  - Resistance profiles of cyclic and linear inhibitors of HIV-1 protease.
AB  - Resistance to anti-HIV protease drugs is a major problem in the design of AIDS
      drugs with long-term efficacy. To identify structural features associated with a
      certain resistance profile, the inhibitory properties of a series of symmetric
      and asymmetric cyclic sulfamide, cyclic urea and linear transition-state analogue
      inhibitors of HIV-1 protease were investigated using wild-type and mutant enzyme.
      To allow a detailed structure-inhibition analysis, enzyme with single, double,
      triple and quadruple combinations of G48V, V82A, 184V and L90M substitutions was
      used. Kinetic analysis of the mutants revealed that catalytic efficiency was 1
      30% of that for the wild-type enzyme, a consequence of reduced kcat in all cases
      and an increased KM for all mutants except for the G48V enzyme. The overall
      structure-inhibitory profiles of the cyclic compounds were similar, and the
      inhibition of the V82A, 184V and G48V/L90M mutants were less efficient than of
      the wild-type enzyme. The greatest increase in Ki was generally observed for the
      184V mutant and least for the G48V/L90M mutant, and additional combinations of
      mutations did not result in improved inhibition profiles for the cyclic
      compounds. An extended analysis of additional mutants, and including a set of
      linear compounds, showed that the profile was unique for each compound, and did
      not reveal any general structural features associated with a certain inhibition
      profile. The effects of structural modifications in the inhibitors, or of
      mutations, were not additive and they differed depending on their context. The
      results demonstrate the difficulties in predicting resistance, even for closely
      related compounds, and designing compounds with improved resistance profiles.

PMID- 12180646
TI  - Hepatic and intestinal contributions to pharmacokinetic interaction of indinavir
      with amprenavir, nelfinavir and saquinavir in rats.
AB  - To elucidate the aspects of pharmacokinetic interactions among HIV protease
      inhibitors (PIs), we investigated the effects of indinavir (IDV) on the hepatic
      and intestinal first-pass metabolism of other HIV PIs, amprenavir (APV),
      saquinavir (SQV) and nelfinavir (NFV), in rats. After oral co-administration with
      IDV, the area under the concentration versus time curves (AUC) of APV, SQV and
      NFV increased significantly by 1.6-, 9.5- and 2.3-fold, respectively, compared
      with mono-administration. After intravenous administration, the AUC of APV, SQV
      and NFV also increased in the presence of IDV by 1.4-, 1.2- and 1.5-fold,
      respectively. Mean concentrations of APV, SQV and NFV in the liver extracellular
      fluid, measured using a liver microdialysis method, were very low compared with
      their Michaelis constants regardless of co-administration of IDV, suggesting that
      APV, SQV and NFV metabolism follows linear kinetics in the liver. This finding
      also indicates that metabolism of PIs depended on the metabolic clearance rate in
      the liver microsomes. The oral bioavailability of SQV in the presence of IDV
      increased markedly by 8.5-fold, and that of APV and NFV also increased by 1.2-
      and 1.5-fold, respectively. On the basis of the well-stirred model, the hepatic
      availabilities of APV, SQV and NFV in the presence of IDV increased by 1.1-, 1.4-
      and 1.5-fold, and the intestinal availabilities increased by 1.1-, 6.2- and 1.1
      fold, respectively. These results suggest that both hepatic and intestinal
      metabolism were essentially involved in the interactions between IDV and other
      HIV PIs, and the degree of those contributions varied with each combination of
      HIV PIs.

PMID- 12180649
TI  - Antiviral activity of brassinosteroids derivatives against measles virus in cell
      cultures.
AB  - Twenty-seven brassinosteroid derivatives were tested for antiviral activity
      against measles virus (MV) via a virus-yield reduction assay. Compounds 6b
      [(22S,235)-3beta-bromo-5alpha,22,23-trihydroxystigmastan-6-one], 1d [(22R,23R)
      2alpha,3alpha,22,23-tetrahydroxy-beta-Homo-7-oxa-stigmastan-6-one], 8a [(22R,23R)
      3beta-fluoro-22,23-dihydroxystigmastan-6-one], 9b [(22S,23S)-3beta-fluoro
      5alpha,22,23-trihydroxystigmastan-6-one] and 10b [(22S,23S)-5alpha-fluor
      3beta,22,23-trihydroxystigmastan-6-one], with selectivity indexes (SI) of 40, 57,
      31, 37 and 53, are the derivatives with good antiviral activity against MV. These
      SI values are higher than those obtained with ribavirin (used as reference drug).
      A comparative analysis of 50% cytotoxic concentration (CC50) values, using
      confluent non-growing cells, gives and indication of structure-activity
      relationship. According to their degree of cytotoxicity the compounds were
      divided in three groups: low, intermediate and high cytotoxicity. By observing
      the chemical structures of compounds belonging to the first group we can see that
      less cytotoxic activities are related to the presence of a 3beta-hydroxy group on
      C-3 (ring A) and a double bond between C-22 and C-23 (side chain). The
      replacement of a 5alpha-hydroxy group by a 5alpha-fluoro group enhances
      cytotoxicity. Halogenated brassinosteroid derivatives in C-3 position are more
      cytotoxic than those with an acetoxy group in the same position. For compounds
      1d, 6b, 10b and ribavirin, cytotoxicity measurements were also done with
      replicating cells; CC50 values were low, but they still competed favourably with
      ribavirin against MV.

PMID- 12180648
TI  - Coumarins and pyranocoumarins, potential novel pharmacophores for inhibition of
      measles virus replication.
AB  - A series of coumarin and pyranocoumarin analogues were evaluated in vitro for
      antiviral efficacy against measles virus (MV), strain Chicago. Of the 22
      compounds tested for inhibition, six were found to have selectivity indices
      greater than 10. These were compounds 5-hydroxy-7-propionyloxy-4-propylcoumarin
      (2a), 5,7-bis(tosyloxy)-4-propylcoumarin (7); 5-hydroxy-4-propyl-7-tosyloxy
      coumarin (8); 6,6-dimethyl-9-propionyloxy-4-propyl-2H,6H-benzo[1,2-b:3,4
      b']dipyran-2-one (9); 6,6-dimethyl-9-pivaloyloxy-4-propyl-2H,6H-benzo[1,2-b:3,4
      b']dipyran-2-one (10); and 7,8-cis-10,11,12-trans-4-propyl-6,6,10,11-tetramethyl
      7,8,9-trihydroxy-2H,6H,12H-benzo[1 ,2-b:3,4-b':5,6-b'']tripyran-2-one (18). Three
      of the active drugs were propyl coumarin analogues (2a, 7 and 8), two were
      dipyranone or chromeno-coumarins (9 and 10), and one was a benzotripyranone with
      a coumarin nucleus (18). Some appeared to be rather specific and potent
      inhibitors of MV with EC50 values ranging from 0.2 to 50 microg/ml and the
      majority of the EC50 values being less than 5 pg/ml. The compounds inhibited an
      additional nine strains of MV, and in virucidal tests the drugs did not
      physically disrupt the virion to inhibit virus replication. The inhibitory
      activity for one of the compounds tested (7) was somewhat dependent on virus
      concentration and it was still active when added to cells up to 24 h after virus
      exposure. When used in combination with ribavirin, compound 7 appeared not to
      profoundly affect the antiviral efficacy of ribavirin or its cell-associated
      toxicity. However, a slightly antagonistic MV-inhibitory effect was observed at
      the highest concentration of ribavirin used in combination with most
      concentrations of compound 7 tested. This and related compounds may be valuable
      leads in the development of a potent and selective class of MV inhibitors that
      could be used in future in the clinic.

PMID- 12180650
TI  - Some issues of environmental concern in Kampala, the capital city of Uganda.
AB  - Kampala, the capital city of Uganda is the administrative, political, commercial,
      industrial, educational and cultural centre of Uganda. The city has an area of
      190 km2 and is located 8 km north of Lake Victoria (the second largest fresh
      water lake in the world) and approximately 42 km north of the equator. The
      population varies from about 1.2 million during the day to perhaps 0.9 million at
      night. The anthropogenic activity of this population far exceeds the
      infrastructure capacity of the city, leading to the deterioration of the urban
      environment. This article highlights the major sources of environmental
      degradation and pollution in the city, which include solid waste, abattoir waste,
      sewage, sanitation, drainage, industrial pollution, traffic pollution,
      atmospheric pollution, urban agriculture, rapid urbanisation and water hyacinth.

PMID- 12180651
TI  - Mesophilic biomethanation and treatment of poultry waste-water using pilot scale
      UASB reactor.
AB  - The feasibility of applying the up-flow anaerobic sludge blanket (UASB) treatment
      for poultry waste (faeces) water was examined. A continuous-flow UASB pilot scale
      reactor of 3.50 L capacity using mixed culture was operated for 95 days to assess
      the treatability of poultry waste-water and its methane production. The maximum
      chemical oxygen demand (COD) removed was found to be 78% when organic loading
      rate (OLR) was 2.9 kg COD m(-3) day(-1) at hydraulic retention times (HRT) of
      13.2 hr. The average biogas recovery was 0.26 m3 CH4 kg COD with an average
      methane content of 57% at mean temperature of 30 degrees C. Data indicate more
      rapid methanogenesis with higher loading rates and shorter hydraulic retention
      times. At feed concentration of 4.8 kg COD m(-3) day(-1), anaerobic digestion was
      severely retarded at all hydraulic retention time tested. This complication in
      the reactor operations may be linked to build-up of colloidal solids often
      associated with poultry waste water and ammonia toxicity. Isolates from granular
      sludge and effluent were found to be facultative anaerobes most of which were
      Pseudomonas genera.

PMID- 12180652
TI  - Trace metal concentration in scalp hair of occupationally exposed autodrivers.
AB  - The concentrations of Cr, Pb, Zn, Cu, Ni and Cd were analyzed by Atomic
      Absorption Spectrophotometer in the scalp hair of professional male autodrivers
      who are occupationally exposed to the vehicular/industrial pollutants in the
      industrial city of Coimbatore, Tamil Nadu. The unwashed hair samples when
      compared with the washed hair showed a significantly higher levels of Cr, Zn and
      Pb. The correlation coefficient showed a strong mutual dependence on the scalp
      hair of the exposed individuals and no correlation was found among the trace
      metals except for Ni-Pb and Ni-Cd. The results in general showed a positive
      exogenous contribution of all the analyzed industrial trace metals. The drivers
      who are occupationally exposed to vehicular/industrial pollution are at risk.

PMID- 12180654
TI  - Emission of nitrous oxide from rice-wheat systems of Indo-Gangetic plains of
      India.
AB  - Nitrous oxide (N2O) accounts for 5% of the total enhanced greenhouse effect and
      responsible for the destruction of the stratospheric ozone. The rice-wheat
      cropping system occupying 26 million ha of productive land in Asia could be a
      major source of N2O as most of the fertilizer N in this region is consumed by
      this system. Emission of N2O as influenced by application of urea, urea plus farm
      yard manure (FYM), and urea plus dicyandiamide (DCD), a nitrification inhibitor,
      was studied in rice-wheat systems of Indo-Gangetic plains of India. Total
      emission of N2O-N from the rice-wheat systems varied between 654 g ha(-1) in
      unfertilized plots and 1,570 g ha(-1) in urea fertilized plots. Application of
      FYM and DCD reduced emission of N2O-N in rice. The magnitude of reduction was
      higher with DCD. In wheat also N2O-N emission was reduced by DCD. FYM applied in
      rice had no residual effect on N2O-N emission in wheat. In rice intermittent
      wetting and drying condition of soil resulted in higher N2O-N emission than that
      of saturated soil condition. Treatments with 5 irrigations gave higher emissions
      in wheat than those with 3 irrigations. In rice-wheat system, typical of a
      farmer's field in Indo-Gangetic plains, where 240 kg N is generally applied
      through urea, N2O-N emission is 1,570 g ha(-1) (0.38% of applied N) and
      application of FYM and DCD reduced it to 1,415 and 1,096 g ha(-1), respectively.

PMID- 12180653
TI  - The distribution of molybdenum in the tissues of wild ducks.
AB  - The Mo contents and the relations between Mo and Cu or Cr contents were
      investigated in the organs of Japanese wild ducks (spotbill duck, pintail,
      wigeon, scaup and tufted duck). The highest Mo content in kidney and liver of the
      dabbling ducks were more than 30 microg g(-1) dry weight (microg g(-1) d. wt.),
      though that of diving ducks were less than 11 microg g(-1) d. wt. The contents
      were lower in the ducks migrating within Japan, Eurasia and North America than
      those in the birds migrating between Japan and Eurasia. The contents of liver in
      all species were more than 50 and less than 5 microg g(-1) d. wt. for Cu and Cr,
      respectively. Significant correlations were found between Mo and both elements in
      pintail and scaup, and Mo and Cr in tufted duck. These results suggest that the
      contamination of wild ducks reflects the reproductive area, and not the collected
      area. Mo contents closely correlated with the Cu and/or Cr contaminations.

PMID- 12180655
TI  - Possible biological significance of contaminated sediments in Port Jackson,
      Sydney, Australia.
AB  - Comprehensive investigations of estuaries in central New South Wales has
      identified Port Jackson as the most contaminated waterway on the eastern seaboard
      of Australia. Extensive areas of the estuary are mantled in sediment containing
      high concentrations of a large range of metallic and organic contaminants.
      Although extensive, this database does not provide an effective basis for
      determining the potential adverse effects of chemicals on living resources. In
      the absence of any ecotoxicological information, the recently published (1999)
      draft Australian and New Zealand Environmental and Conservation Council (ANZECC)
      sediment quality guidelines have been used to assess possible adverse biological
      effects of these toxicants. The ANZECC guidelines use the lower effects range of
      the widely used U. S. National Oceanic and Atmospheric Administration (NOAA)
      scheme to identify potentially contaminated sediment and as a threshold to
      trigger for additional investigative work. This guideline level has been used in
      the current study to assess possible toxicity of contaminated sediments in Port
      Jackson. It is estimated that sediments in approximately 26% of the estuary,
      mainly the upper parts of the harbour and much of the central harbour, have a 67%
      probability of being toxic. Sediments in the central harbour and a major
      tributary, the Middle Harbour, comprising about 40% of the estuary, have a 13 to
      25% probability of toxicity. All sediments in the harbour, except at the mouth of
      the estuary, would require additional environmental assessment based on the
      proposed draft ANZECC sediment quality guidelines.

PMID- 12180656
TI  - Evaluating the heavy metal contamination in sediments from the guadalquivir
      estuary after the Aznalcollar mining spill (SW Spain): a multivariate analysis
      approach.
AB  - The Donana National Park is one of the most important Natural Reserves in west
      Europe. The park and the Guadalquivir estuary were impacted by the release of 5
      million cubic meters of acid waste from the processing of pyrite ore. Here are
      presented a multivariate analysis approach to evaluate the extension and the
      magnitude of the accidental spill on the estuarine sediments. Sediments were used
      to analyze 6 different metals (Fe, Mn, Zn, Cd, Pb, Cu). Also the concentration of
      the metals in the different geochemical sediment fractions were determined as a
      means of assessing the potential impact of the acid water from the mine. The
      analysis of the results obtained permits to establish that the impact of the
      accident was acute on the ecosystem due to the set up of a treatment plan in June
      1998 and to the high hydrodynamic of the estuary that absorb the early impact.
      Chronic contamination by Cu was also detected during the monitoring of the impact
      of the accident in the estuary but this did not appear to be related to the
      accidental spill. Because the likelihood of long term adverse effects from the
      heavy metal contamination of estuarine sediments, further ecotoxicological
      evaluations should be carried out for the estuary and the park using an
      integrated approach.

PMID- 12180657
TI  - Sediments and sediment-derived soils in Illinois: pedological and agronomic
      assessment.
AB  - Dredging sediments from water bodies in Illinois is done to preserve reservoir
      capacity, maintain navigation and recreation channels, and restore habitats, but
      the fate of the sediments is an issue. In anticipation of a major sediment
      dredging operation in Lake Peoria in the Illinois River, a retrospective study of
      sediment placement operations was performed. Sediments previously dredged from
      reservoirs and placed in retaining ponds were sampled along with adjacent upland
      soils which served as references. Sediments from the Illinois River above Peoria
      were sampled from islands, river bottom, and adjacent floodplain. Dredged
      sediment retention ponds initially support wetland vegetation. After dewatering,
      the physical properties of sediments tend to become similar to upland soils and
      the retention basins are then able to support conventional agriculture. Sediment
      organic matter content was similar to local reference surface soils, and soil pH
      of the sediments was neutral or above. Sediment textures are dominated by silts
      and clays, with the Lake Peoria samples being most clayey. Calcium was the
      dominant cation in all the samples, and micronutrients measured were in adequate
      supply for plant growth. However, because the Illinois River watershed includes
      industrial inputs, river sediments contained elevated levels of some metals, but
      they were generally below levels of regulatory concern. Results indicated that
      properly handled dredge sediments could make high quality agricultural soils. In
      addition, sediment placement on poor soils could improve their productivity.

PMID- 12180658
TI  - Intradermal test reactivity to Malassezia pachydermatis in healthy basset hounds
      and basset hounds with Malassezia dermatitis.
AB  - Nineteen healthy beagles, eight healthy basset hounds and 17 basset hounds with
      Malassezia dermatitis were tested intradermally with two extracts of M
      pachydermatis. One healthy beagle and two affected basset hounds showed wheal and
      flare reactions 15 minutes after the injection. Delayed reactions, consisting of
      erythematous macules and plaques, were commonly observed 24 hours after the
      injection in both the healthy and affected basset hounds, but occurred
      infrequently in the beagles. At 24 hours the diameters of the lesions in the
      healthy and affected basset hounds were significantly (P<0.01) greater than those
      in the healthy beagles, but the diameters in the healthy and affected basset
      hounds did not vary significantly. Delayed reactions in six of the basset hounds
      with Malassezia dermatitis were characterised histologically by superficial
      perivascular and periadnexal infiltrates of neutrophils and lymphocytes.

PMID- 12180659
TI  - Risk-based evaluation of postmortem inspection procedures for pigs in Australia.
AB  - The results of traditional (incision) and risk-based (visual) postmortem
      inspection procedures were compared on groups of approximately 30,000 pigs. The
      performance characteristics used as a basis for comparison included the non
      detection rates of grossly detectable abnormalities, the microbiological
      contamination rates of carcases and boned product, the association of reactive
      lymph nodes with carcase condemnation and the achievement of 'finished product
      standards' for 'wholesomeness'. It was estimated that 6 per cent of all cases of
      abscessation and 28 per cent of all cases of arthritis were undetected by the
      traditional method, and the comparable figures for the risk-based procedure were
      19 per cent and 39 per cent. However, when the rates of contamination of
      undetected abnormalities with foodborne hazards and other carcase contamination
      parameters were taken into account, it was concluded that both inspection systems
      were likely to result in a very similar level of consumer protection. Any
      increase in potential exposure to foodborne hazards in the abnormalities
      undetected by risk-based inspection would be insignificant in comparison with the
      potential exposure to foodborne hazards resulting from contaminated 'normal'
      lymph nodes and carcase surfaces. There were no statistically significant
      differences between the two procedures in the contamination rates of pre-chill
      carcases or boned retail products with Salmonella and Yersinia species.

PMID- 12180660
TI  - Epidemiological investigations of outbreaks of bovine ephemeral fever in Israel.
AB  - In two epidemics of bovine ephemeral fever (BEF) in Israel, one in 1990 and one
      in 1999, the virus was probably carried by vectors transported by air currents
      across the Rift Valley and through the Red Sea trough. The disease broke out
      under optimal ecological conditions among vulnerable cattle populations and
      spread rapidly; it developed in the spring and summer and ended soon after the
      daily average ambient temperature fell below 16 degrees C in late autumn. The
      proportion of herds affected reached 78.4 and 97.7 per cent in 1990 and 1999,
      respectively. The highest rates of incidence, morbidity and mortality were
      recorded in dairy cattle herds in the Jordan Valley, the initial focus of the
      outbreaks, with a morbidity of 20 and 38.6 per cent in 1990 and 1999,
      respectively, and mortality among the affected animals of 2 and 8.6 per cent in
      1990 and 1999, respectively. In 1991, the disease recurred sporadically in the
      central and southern regions of Israel in only three herds, but in 2000 the
      disease returned on an epidemic scale, and 85 per cent of herds were affected,
      with morbidity and mortality rates of 4-3 and 0-3 per cent, respectively. In the
      1999 epidemic, the morbidity rate decreased from 38-6 per cent on average in the
      Jordan Valley to 12.8 per cent in the inner valleys and 5.3 per cent on the
      Mediterranean coastal plain, but the mortality rate increased from 8-6 per cent
      in the Jordan Valley to 14-3 per cent in the inner valleys, and to 28 per cent on
      the Mediterranean coastal plain, where the outbreak declined. An average of 2-7
      per cent of the animals experienced a second attack of the disease two to six
      weeks later. The epidemic in 2000 was milder and shorter than that in 1999. All
      the cattle affected in both outbreaks were more than three months old. The
      vector(s) is not known for certain but the available evidence indicates that
      mosquitoes, and not Culicoides species, are the natural vectors of BEF virus in
      Israel.

PMID- 12180661
TI  - Arrest of metaphyseal ossification in pigs with experimental classical swine
      fever.

PMID- 12180662
TI  - Pancreatic atrophy in a peregrine falcon (Falco peregrinus).

PMID- 12180663
TI  - Meat from animals vaccinated against FMD.

PMID- 12180664
TI  - FMD in a parturient sheep flock.

PMID- 12180665
TI  - FMD in a parturient sheep flock.

PMID- 12180666
TI  - Need for continued awareness of BSE.

PMID- 12180667
TI  - Revised LVI stamp and appointment process.

PMID- 12180668
TI  - Future of the RCVS library.

PMID- 12180669
TI  - Bilateral patella ligament rupture in a llama.

PMID- 12180670
TI  - Predictions for rapid methods and automation in food microbiology.
AB  - A discussion is presented on the present status of rapid methods and automation
      in microbiology. Predictions are also presented for development in the following
      areas: viable cell counts; real-time monitoring of hygiene; polymerase chain
      reaction, ribotyping, and genetic tests in food laboratories; automated enzyme
      linked immunosorbent assay and immunotests; rapid dipstick technology; biosensors
      for Hazard Analysis Critical Control Point programs; instant detection of target
      pathogens by computer-generated matrix; effective separation and concentration
      for rapid identification of target cells; microbiological alert systems in food
      packages; and rapid alert kits for detecting pathogens at home.

PMID- 12180671
TI  - AOAC Task Group creates a much-needed document outlining microbiology criteria
      for method validation.

PMID- 12180672
TI  - Two ephedra methods successfully refined, validated, and now advanced to the AOAC
      collaborative study.

PMID- 12180673
TI  - Kinetic spectrophotometric determination of atenolol in dosage forms.
AB  - A simple kinetic procedure is described for the determination of atenolol in its
      dosage forms. The procedure is based on coupling the drug with 4-chloro-7
      nitrobenzo-2-oxa-1,3-diazole in pH 8 borate buffer at the boiling temperature for
      a fixed time of 30 min, and then measuring the absorbance of the reaction product
      at 460 nm. The absorbance-concentration plot is rectilinear over the range 5-50
      microg/mL with a minimum detection limit of 1.3 microg (4.9 x 10(-6) M). The
      determination of atenolol by the fixed-concentration and rate-constant methods is
      also feasible with the calibration equations obtained, but the fixed-time method
      proved to be more applicable. The procedure was applied successfully to
      commercial tablets, and statistical analysis showed that the results compared
      favorably with those obtained by the official methods. The interference likely to
      be introduced from some coformulated drugs and the effect of sensitizers and
      surfactants on the performance of the proposed method were also studied. A
      proposed reaction pathway is presented.

PMID- 12180675
TI  - Measurement of cis and trans isomers of vitamin K1 in rat tissues by liquid
      chromatography with a C30 column.
AB  - The purpose of this study was to validate a method for measuring vitamin K
      isomers in rat tissues by liquid chromatography (LC) with fluorescence detection
      after simple solvent extraction. This method uses separation on a C30 column,
      followed by zinc reduction and fluorescence measurement (243 nm, excitation; 430
      nm, emission) to detect and quantitate vitamin K isomers. We were able to
      separate cis- and trans-vitamin K1 in methylene chloride extracts of homogenized
      rat livers and in hexane extracts of rat plasma. Tissue extracts were evaporated
      and rediluted with tetrahydrofuran-methanol (1 + 1) or methanol before being
      injected under isocratic conditions onto the LC column. Liver tissue of Fischer
      344 rats fed a vitamin K1-containing diet ad libitum contained approximately 20
      and 60 ng/g cis- and trans-vitamin K1, respectively. Mean recoveries of vitamin
      K1 isomers from spiked liver were 92 +/- 11% for cis-vitamin K1 and 106 +/- 5%
      for trans-vitamin K1. We recovered 96 +/- 8% of trans-vitamin K1 added at 1, 3,
      and 6 ng/mL to plasma (containing an endogenous level of 4 ng/g) from the same
      rats; we recovered 112 +/- 5% when trans-vitamin K1 was added to human serum
      (National Institute of Standards and Technology Standard Reference Material
      968C). This direct method shows significant potential for the selective
      measurement of vitamin K1 isomers in tissues.

PMID- 12180674
TI  - Development and validation of a cost-effective, efficient, and robust liquid
      chromatographic method for the simultaneous determination of the acetyl and
      succinoyl content in hydroxypropyl methylcellulose acetate succinate polymer.
AB  - A reversed-phase liquid chromatographic method was developed and validated for
      the determination of the content of free acetic acid, free succinic acid, acetyl
      substituents, and succinoyl substituents in hydroxypropyl methylcellulose acetate
      succinate (HPMCAS; Chemical Abstracts Service Registry No. 71138-97-1) polymer.
      This single new method gave accurate and precise measurement of both acetyl and
      succinoyl substituents, which had previously required 3 Japanese Pharmaceutical
      Excipients (JPE) methods to accomplish. Consequently, analysis time and
      turnaround time are decreased significantly. Furthermore, this method can also
      separate and determine the free acetic and succinic acids in HPMCAS polymer, a
      task that the corresponding JPE method cannot achieve. The values for accuracy
      (average recovery from 12 standard samples) were 99.9% for acetic acid and 99.8%
      for succinic acid. The values for injection precision (relative standard
      deviation [RSD]) were 0.11% for acetic acid and 0.28% for succinic acid. The
      values for intermediate precision (RSD) were 1.25% for determination of the
      acetyl content at the 8.78% (w/w) level and 1.33% for determination of the
      succinoyl content at the 10.9% (w/w) level. The values for intermediate precision
      (RSD) were 5.98% for determination of free acetic acid at the 0.12% (w/w) level
      and 5.13% for determination of free succinic acid at the 0.029% (w/w) level. The
      method was proven to be robust with respect to variation in the pH of the mobile
      phase, the concentration of potassium dihydrogen phosphate, and the flow rate.
      The method is well suited for quality control in today's fast-paced
      pharmaceutical laboratories.

PMID- 12180676
TI  - Detection and identification of zeranol in chicken or rabbit liver by liquid
      chromatography-electrospray tandem mass spectrometry.
AB  - A sensitive, specific, and reliable liquid chromatography tandem mass
      spectrometry (LC-MS/MS) method was developed for detection and identification of
      zeranol in chicken or rabbit liver. A homogenized liver sample was hydrolyzed
      with beta-glucuronidase/arylsulfatase, and the hydrolysate was extracted with
      ethyl ether. The supernatant was evaporated to dryness, and the residue was
      dissolved in chloroform and re-extracted with sodium hydroxide. After
      acidification, the extract was cleaned up on a C18 solid-phase extraction
      cartridge and analyzed by electrospray LC-MS/MS in the negative ion mode. The
      multiple reaction monitoring transition from both m/z 321 to 277 and m/z 321 to
      303 was monitored for confirmation, and the product ion of 277 was used for
      quantitation. Separation was performed on a Waters XTettra C18 column (50 x 2.1
      mm, 3.5 microm) combined with a safeguard column (Symmetry C18, 20 x 3.9 mm, 5
      microm), using a gradient elution with acetonitrile and 20 mM ammonium acetate.
      Calibration curves were prepared and good linearity was achieved over the
      concentration ranges tested. For all liver samples fortified at 3 different
      levels of 1, 5, and 50 microg/kg, the overall recoveries and relative standard
      deviations were in the range of 61-90 and 8-13%, respectively. The limit of
      quantitation based on the assay validation was 1 microg/kg. The method had been
      used on a routine basis for detection and identification of zeranol in liver
      samples.

PMID- 12180677
TI  - Determination of sulfonamide residues in eggs by liquid chromatography.
AB  - A method was developed for determining residual sulfonamide antibacterials such
      as sulfamethazine (SMZ), sulfamonomethoxine (SMM), sulfadimethoxine (SDM), and
      sulfaquinoxaline (SQ) in eggs using liquid chromatography with a photodiode array
      detector. The spiked and blank samples were cleaned up by using an Ultrafree
      MC/PL centrifugal ultrafiltration unit. A Mightysil RP-4 GP column and a mobile
      phase of 28% (v/v) ethanol-H2O with a photodiode array detector were used for the
      determination. Average recoveries from eggs spiked with each drug at 0.1, 0.2,
      0.4, and 1.0 ppm were > or = 80.9%, with relative standard deviations between 1.3
      and 4.7%. The limits of quantitation were 0.060 ppm for SMZ, 0.045 for SMM, 0.044
      for SDM, and 0.093 for SQ. The analysis of one sample required < 30 min and < 5
      mL ethanol as solvent.

PMID- 12180678
TI  - Quantitative LC/MS-MS determination of sulfonamides and some other antibiotics in
      honey.
AB  - A simple and rapid method was developed for the determination of 20 antibiotics
      (sulfonamides, tetacyclines, and flumequine) in honey by liquid chromatography
      tandem mass spectrometry. The proposed method is sensitive (limit of detection
      0.5 to 10 ppb for the various antibiotics) and selective. A hydrolysis step
      ensures the liberation of sugar-bound sulfonamides. The approach has been used to
      analyze some 300 honey samples. A number of them were found to have exceeded the
      Swiss limit of 50 ppb.

PMID- 12180679
TI  - Simultaneous determination of codeine and pyridoxine in pharmaceutical
      preparations by first-derivative spectrofluorimetry.
AB  - A method for the simultaneous determination of codeine and pyridoxine was
      developed, based on the measurement of their native fluorescence signals, by
      using first-derivative spectrofluorimetry to resolve the mixture. Codeine was
      measured at lambda(em) = 309 nm, and pyridoxine was measured at lambda(em) = 450
      nm. Instrumental parameters were optimized, and the emission spectra were
      recorded between 275 and 475 nm, at lambda(ex) = 255 nm and excitation and
      emission slit widths of 2.5 and 10 nm, respectively. Systematic studies on the
      influence of species usually present along with the analytes (such as caffeine,
      ascorbic acid, paracetamol, and thiamine) were also performed. The calibration
      graphs were linear over the ranges of 0.5-7.0 and 0.1-1.0 microg/mL for codeine
      and pyridoxine, respectively, and the relative standard deviations (n = 10) were
      about 3%. The method was successfully applied to the determination of codeine and
      pyridoxine in solutions of synthetic mixtures and in synthetic and semisynthetic
      pharmaceutical formulations.

PMID- 12180680
TI  - A new, sensitive, and rapid spectrophotometric method for the determination of
      sulfa drugs.
AB  - A sensitive, rapid, and simple spectrophotometric method is described for the
      determination of sulfa drugs. The method is based on the formation of a red
      colored product by the diazotization of sulfonamides such as sulfathiazole (SFT),
      sulfadiazine (SFD), sulfacetamide (SFA), sulfamethoxazole (SFMx), sulfamerazine
      (SFMr), sulfaguanidine (SFG), and sulfamethazine (SFMt), followed by complexation
      with dopamine in the presence of molybdate ions in (1 + 1) H2SO4 medium.
      Absorbance of the resulting red product is measured at 490-510 nm, and the
      product is stable for 2 days at 27 degrees C. Beer's law is obeyed in the
      concentration range of 0.04-8.0 microg/mL at the wavelength of maximum
      absorption. The method was used successfully for the determination of some
      sulfonamides in tablets and eye drops. Common excipients used as additives in
      pharmaceuticals do not interfere in the proposed method. The method offers the
      advantages of simplicity, rapidity, and sensitivity without the need for
      extraction or heating. The limits of detection and quantitation were calculated
      for SFT, SFD, SFA, SFMx, SFMr, SFG, and SFMt.

PMID- 12180681
TI  - Spectrophotometric determination of phenylephrine hydrochloride in
      pharmaceuticals by flow injection analysis exploiting the reaction with potassium
      ferricyanide and 4-aminoantipyrine.
AB  - This paper presents a method for the determination of phenylephrine hydrochloride
      in pharmaceuticals by spectrophotometric flow injection analysis exploiting the
      reaction with potassium ferricyanide and 4-aminoantipyrine, which leads to the
      formation of a condensation product with strong absorptivity at 500 nm. The
      linear dynamic range was between 0.95 and 9 mg/L, with a limit of detection of
      0.2 mg/L and a sampling throughput of 120 samples per hour. The method was
      applied to eyewashes and nasal decongestant liquid medicines.

PMID- 12180682
TI  - Biosensor immunoassay of ivermectin in bovine milk.
AB  - A rapid and sensitive biosensor immunoassay was developed for determination of
      ivermectin residues in bovine milk. A detection limit of 16.2 ng/mL was achieved.
      A Biacore optical biosensor based on surface plasmon resonance was used, and a
      range of extraction techniques was investigated. In the final assay procedure,
      ivermectin was extracted with acetonitrile followed by C8 solid-phase extraction
      cleanup. It was proven experimentally that 2 methods of milk storage, freezing or
      addition of mercury-containing compounds as preservatives, could be used without
      considerable change in detected concentrations (samples were fortified with
      ivermectin after storage). The average values for milk samples spiked at 100 and
      50 ng/mL concentrations were 102.6 and 51.5 ng/mL, respectively. Extraction and
      analysis of 20 milk samples were performed within a single working day.

PMID- 12180683
TI  - Simultaneous determination of estradiol and medroxyprogesterone acetate in
      pharmaceutical formulations by second-derivative spectrophotometry.
AB  - This paper reports a simple and fast method for the simultaneous determination of
      estradiol (ED) and medroxyprogesterone acetate (MP) in pharmaceutical
      formulations by second-derivative spectrophotometry. Methanol was used to extract
      the drugs from formulations, and subsequently the extracts were evaluated
      directly by derivative spectrophotometry. The drugs were determined
      simultaneously by using the graphic method at 297.4 nm for ED and the zero
      crossing method at 273.4 nm for MP. If both compounds are present together in a
      sample, it is possible to quantitate one in the presence of the other. The best
      signal-to-noise ratio was found when the second derivative of the spectrum was
      used. The linear ranges for determination of the drugs were 4.7 x 10(-6) to 1.6 x
      10(-4) and 7.2 x 10(-6) to 2.0 x 10(-4) mol/L for ED and MP, respectively. The
      ingredients commonly found in commercial pharmaceutical formulations do not
      interfere with the determination. Chemical and spectral variables were optimized
      for the determination of both analytes. Good levels of repeatability (relative
      standard deviation), 1.4 and 1.9%, were obtained for ED and MP, respectively. The
      proposed method was applied to the determination of these drugs in pharmaceutical
      formulations.

PMID- 12180684
TI  - Liquid chromatographic determination of ampicillin residues in porcine muscle
      tissue by a multipenicillin analytical method: European Collaborative Study.
AB  - A collaborative study involving 14 laboratories was conducted to determine
      residues of ampicillin in porcine muscle tissue by using a liquid chromatographic
      method developed for multipenicillin analysis that can quantitate 8 penicillin
      compounds (benzylpenicillin, phenoxymethylpenicillin, ampicillin, amoxicillin,
      nafcillin, oxacillin, cloxacillin, and dicloxacillin) at trace levels in muscle
      tissue. This method involves extraction of the penicillins with phosphate buffer,
      pH 9, followed by cleanup and concentration on a C18 solid-phase extraction
      column and reaction with benzoic anhydride at 50 degrees C and with 1,2,4
      triazole and mercury(II) chloride solution, pH 9.0, at 65 degrees C. The
      derivatized compounds are eluted isocratically on a C8 column with a mobile phase
      of acetonitrile and phosphate buffer (pH 6; 0.1 M) containing sodium thiosulfate
      and the ion-pair reagent tetrabutylammonium hydrogen sulfate. The penicillins are
      detected by UV absorption at 325 nm. The limit of detection and the limit of
      determination (quantitation) of the method were calculated to be approximately 3
      5 and 25 microg/kg, respectively, in accordance with the criteria of European
      Union (EU) Decision No. 93/256/EEC. In this first interlaboratory study,
      collaborators were instructed to monitor 4 different penicillin compounds
      (benzylpenicillin, phenoxymethylpenicillin, ampicillin, and amoxicillin) by
      analyzing 8 blind samples of muscle tissue in triplicate. These samples were
      prepared from 2 materials containing different concentrations of incurred
      ampicillin (63.5 microg/kg for material No. 1 and 358.1 microg/kg for material
      No. 2) and 1 blank material. The repeatability relative standard deviation and
      the reproducibility relative standard deviation were 10.2 and 17.4%,
      respectively, for material No. 1 and 7.0 and 16.0%, respectively, for material
      No. 2. These results demonstrate that the method is suitable for the
      determination of ampicillin residues in muscle tissue at the EU maximum residue
      limit (50 microg/kg) and above. However, the identification of positives by this
      procedure may need additional confirmation by techniques with greater
      specificity, such as liquid chromatography combined with mass spectrometry, or
      tandem mass spectrometry. Investigations regarding the basis of interlaboratory
      testing studies will further demonstrate the suitability of multiresidue
      methodology for detecting and quantitating other compounds in the family of
      penicillin antibiotics.

PMID- 12180685
TI  - Liquid chromatographic determination of S-adenosyl-L-methionine in dietary
      supplement tablets.
AB  - A simple and reliable liquid chromatographic method was developed for the
      determination of S-adenosyl-L-methionine (SAM) in dietary supplement tablets. SAM
      in products was extracted with a phosphate buffer and separated from the mixture
      on a reversed-phase C8 column by ion-pair chromatography. A gradient mobile phase
      containing phosphate buffer, sodium octanesulfonate as the ion-pair reagent, and
      acetonitrile at a flow rate of 1.2 mL/min was used in the analysis. The UV
      detection wavelength was set at 257 nm. The calibration curve was linear over a
      range of 75-375 microg/mL for the SAM active ion with R2 = 0.9999. Replicate
      tests indicated good reproducibility of the method with a relative standard
      deviation of 0.9% (n = 8). The multiple extractions and recoveries from fortified
      products showed the high accuracy of the analysis. The use of the acidic buffer
      for SAM extraction and elution and the use of a fresh standard for each
      calibration to counteract the instability of the SAM compound significantly
      improved the accuracy of the method.

PMID- 12180686
TI  - DNA microarray technology used for studying foodborne pathogens and microbial
      habitats: minireview.
AB  - Microarray analysis is an emerging technology that has the potential to become a
      leading trend in bacterial identification in food and feed improvement. The
      technology uses fluorescent-labeled probes amplified from bacterial samples that
      are then hybridized to thousands of DNA sequences immobilized on chemically
      modified glass slides. The whole gene or open reading frame(s) is represented by
      a polymerase chain reaction fragment of double-strand DNA, approximately 1000
      base pair (bp) or 20-70 bp single-strand oligonucleotides. The technology can be
      used to identity bacteria and to study gene expression in complex microbial
      populations, such as those found in food and gastrointestinal tracts. Data
      generated by microarray analysis can be potentially used to improve the safety of
      our food supply as well as ensure the efficiency of animal feed conversion to
      human food, e.g., in meat and milk production by ruminants. This minireview
      addresses the use of microarray technology in bacterial identification and gene
      expression in different microbial systems and in habitats containing mixed
      populations of bacteria.

PMID- 12180687
TI  - Simultaneous quantitation of Aspergillus flavus/A. parasiticus and aflatoxins in
      peanuts.
AB  - A method was developed for simultaneous quantitation of Aspergillus flavus/A.
      parasiticus and aflatoxins in peanuts. Peanut samples were ground with an equal
      weight of water in a vertical cutter mixer to produce a slurry. Separate
      subsamples were taken for dilution-plating to determine total colony forming
      units (CFU)/g of A. flavus/A. parasiticus and for liquid chromatographic analysis
      to determine aflatoxin concentrations. Dry-grinding peanuts for homogenization of
      aflatoxins produced high temperatures that killed most of the A. flavus/A.
      parasiticus propagules. Addition of water to produce a slurry kept the
      temperature from rising above levels that killed the fungi. A 7 min grind time
      provided optimal homogenization for both the fungi and aflatoxins, so long as the
      temperature of the slurry did not exceed 45 degrees C. In the analysis of 60
      shelled peanut samples, total aflatoxin concentrations ranged from 0 to 10,000
      ng/g and total A. flavus/A. parasiticus ranged from 1.4 x 10(3) to 3.2 x 10(6)
      CFU/g. Regression analysis showed a significant positive correlation (p < 0.0001)
      between the quantities of A. flavus/A. parasiticus and aflatoxin (R2 = 0.82).

PMID- 12180688
TI  - Characterization of copolymer hydroxybutyrate/hydroxyvalerate from saponified
      vernonia, soybean, and "spent" frying oils.
AB  - Poly(beta-hydroxyalkanoate)s (PHAs) were biosynthesized by Ralstonia eutropha
      (formerly known as Alcaligenes eutrophus) by using saponified soybean, vernonia,
      and "spent" frying oils. These PHAs were isolated and characterized by matrix
      assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI
      TOFMS), gas chromatography/mass spectrometry (GC/MS), proton nuclear magnetic
      resonance spectrometry (1H NMR), and 2-dimensional homonuclear (1H-1H)
      correlation spectroscopy (COSY). The analytical results revealed that the PHAs
      produced from saponified vernonia and soybean oils were copolymers of
      hydroxybutyrate (HB) and hydroxyvalerate (HV), that is, P(HB/HV)s, whereas the
      saponified "spent" frying oil produced only poly(beta- hydroxybutyrate) (PHB)
      homopolymer. MALDI-MS, GC/MS, and NMR independently confirmed the composition of
      the PHAs. Saponified soybean oil and vernonia oil PHAs contained approximately 4
      and 1% HV units, respectively. For comparison, commercial PHB and P(HB/HV),
      produced by R. eutropha by using glucose and a cosubstrate of glucose and
      propionic acid, respectively, as carbon sources, were similarly characterized.

PMID- 12180689
TI  - Statistical approach for risk assessment of aflatoxin sampling plan used by
      manufacturers for raw shelled peanuts.
AB  - Processed food manufacturers often use acceptance sampling plans to screen out
      lots with unacceptable levels of contamination from incoming raw material
      streams. Sampling plan designs are determined by specifying sample sizes, sample
      preparation methods, analytical test methods, and accept/reject criteria.
      Sampling plan performance can be indicated by plotting acceptance probability
      versus contamination level as an operating characteristic (OC) curve. In
      practice, actual plan performance depends on the level of contamination in the
      incoming lot stream. This level can vary considerably over time, among different
      crop varieties, and among locales. To better gauge plan performance, a method of
      coupling an OC curve and crop distributions is proposed. The method provides a
      precise probabilistic statement about risk and can be easily performed with
      commercial spreadsheet software.

PMID- 12180690
TI  - Method validation study of hypoglycin A determination in ackee fruit.
AB  - A study was conducted to validate the performance characteristics of a published
      method entitled "Reversed-Phase Liquid Chromatographic Detection of Hypoglycin A
      in Canned Ackee Fruit Sample." Hypoglycin A (HG-A) was extracted from ackee fruit
      with 80% ethanol-water, centrifuged, and filtered; the sample extract then was
      reacted with phenylisothiocyanate. HG-A was separated by reversed-phase
      chromatography as the phenylthiocarbamyl derivative and detected at the low
      nanogram level using a UV detector at 254 nm. A study was conducted to determine
      recovery of HG-A added to a control ackee fruit sample. A control sample
      containing a low level of HG-A was spiked with 403.2, 201.6, 96.8, and 48.4
      microg HG-A/g ackee fruit, respectively. Twelve replicates were analyzed for each
      spike level. The mean percent recovery +/- standard deviation for spike levels
      403.2, 201.6, 96.8, and 48.4 microg HG-A/g were 94.37 +/- 1.27, 99.12 +/- 2.09,
      107.95 +/- 5.42, and 129.18 +/- 15.32%, respectively. The percent coefficient of
      variation (%CV) for spike levels 403.2, 201.6, 96.8, and 48.4 microg HG-A/g were
      1.35, 2.11, 5.02, and 11.86%, respectively. The recovery data indicate that HG-A
      can be recovered from ackee fruit with excellent accuracy and precision.
      Precision data obtained from replicate assays of ackee fruit naturally
      contaminated with low, medium, and high HG-A levels is presented.

PMID- 12180691
TI  - Real-time detection of genetically modified soya using Lightcycler and ABI 7700
      platforms with TaqMan, Scorpion, and SYBR Green I chemistries.
AB  - A comparative cross platform evaluation of real-time polymerase chain reaction
      detection of DNA sequences present in Roundup Ready soya was undertaken using the
      ABI 7700 and Roche Lightcycler detection systems in combination with 3 different
      detection chemistries: TaqMan, Scorpion primers, and SYBR Green I fluorescent
      dye. Various copy numbers of a plasmid containing the soya lectin sequence were
      used to determine the sensitivity and reproducibility of the different technology
      combinations and to examine both inter and intra machine variability. To examine
      the relative accuracy of each technology, the genetically modified soya content
      of baked products containing known amounts of Roundup Ready soya was determined
      by detection of lectin and the EPSPS transgene. It was determined that the
      combination of TaqMan detection chemistry and the ABI 7700 platform represented
      the best method for quantitative detection of genetically modified organisms in
      terms of both precision and accuracy.

PMID- 12180692
TI  - Rapid determination of thiamine, riboflavin, pyridoxine, and niacinamide in
      infant formulas by liquid chromatography.
AB  - A simplified, simultaneous determination of vitamins B1, B2, B3, and B6 in
      supplemented infant formulas was developed from a single deproteinized sample
      extract, with analysis by reversed-phase, ion-pair chromatography with an
      acidified methanol-water mobile phase. The dioctylsulfosuccinate counter-ion
      facilitates unique retention of the pyridine-based vitamins (niacinamide and
      pyridoxine) and allows for concurrent measurement of both the pyridoxal and
      riboflavin 5'-phosphate endogenous components of milk. Other naturally occurring
      undetected vitamin congeners have minimal analytical significance. UV detection
      is used for niacinamide, and programmed fluorescence detection is used for
      riboflavin and the B6 vitamins. Thiamine is routinely determined sequentially
      under modified elution conditions.

PMID- 12180693
TI  - French laboratory proficiency testing program for food microbiology.
AB  - The proficiency testing program in food microbiology (Reseau d'Analyses et
      d'Echanges en Microbiologie des Aliments; RAEMA), created in 1988, currently
      includes 440 participating laboratories. The program establishes proficiency in
      detection of Salmonella and Listeria monocytogenes, as well as quantitation of
      aerobic microorganisms, Enterobacteriaceae, coliforms, Escherichia coli,
      Clostridium perfringens, coagulase-positive Staphylococcus, and Listeria
      monocytogenes. Twice a year, 5 test samples are sent to participants to assess
      their precision and trueness for enumeration and detection of microorganisms.
      Results show an increasing involvement of food microbiology laboratories in
      quality assurance programs and use of standard and validated analytical methods.
      However, the percentage of laboratories obtaining questionable and unsatisfactory
      microbiological results remains relatively constant.

PMID- 12180694
TI  - Optimized determination of calcium in grape juice, wines, and other alcoholic
      beverages by atomic absorption spectrometry.
AB  - This paper describes a study of the different methods of sample preparation for
      the determination of calcium in grape juice, wines, and other alcoholic beverages
      by flame atomic absorption spectrometry; results are also reported for the
      practical application of these methods to the analysis of commercial samples
      produced in Spain. The methods tested included dealcoholization, dry
      mineralization, and wet mineralization with heating by using different acids
      and/or mixtures of acids. The sensitivity, detection limit, accuracy, precision,
      and selectiviy of each method were established. Such research is necessary
      because of the better analytical indexes obtained after acid digestion of the
      sample, as recommended by the European Union, which advocates the direct method.
      In addition, although high-temperature mineralization with an HNO3-HCIO4 mixture
      gave the best analytical results, mineralization with nitric acid at 80 degrees C
      for 15 min gave the most satisfactory results in all cases, including those for
      wines with high levels of sugar and beverages with high alcoholic content. The
      results for table wines subjected to the latter treatment had an accuracy of
      98.70-99.90%, a relative standard deviation of 2.46%, a detection limit of 19.0
      microg/L, and a determination limit of 31.7 microg/L. The method was found to be
      sufficiently sensitive and selective. It was applied to the determination of Ca
      in grape juice, different types of wines, and beverages with high alcoholic
      content, all of which are produced and widely consumed in Spain. The values
      obtained for Ca were 90.00 +/- 20.40 mg/L in the grape juices, 82.30 +/- 23.80
      mg/L in the white wines, 85.00 +/- 30.25 mg/L in the sweet wines, 84.92 +/- 23.11
      mg/L in the red wines, 85.75 +/- 27.65 mg/L in the rose wines, 9.51 +/- 6.65 mg/L
      in the brandies, 11.53 +/- 6.55 mg/L in the gin, 7.3 +/- 6.32 mg/L in the
      pacharan, and 8.41 +/- 4.85 mg/L in the anisettes. The method is therefore useful
      for routine analysis in the quality control of these beverages.

PMID- 12180695
TI  - Simultaneous determination of nickel, iron, and copper in margarine by
      inductively coupled plasma-atomic emission spectroscopy after sample
      emulsification.
AB  - Nickel, iron, and copper were determined in margarine samples by using
      emulsification followed by inductively coupled plasma-atomic emission
      spectroscopy. Sample treatment and instrumental conditions were optimized, and
      the results were compared with those obtained by a pseudodigestion method in
      order to evaluate the compatibility of both methodologies. The optimum amount of
      margarine in the emulsion was 35% when the surfactant Tween 80 was added as the
      emulsifier. Copper was below the detection limits of both methodologies, i.e.,
      digestion and emulsion; iron and nickel concentrations found by both
      methodologies were similar. The detection limits of the emulsion method were
      0.002, 0.015, and 0.092 mg/kg for copper, iron, and nickel, respectively. A
      benefit of the emulsion method is that laborious and lengthy sample digestion
      procedures are avoided. In addition, accurate and precise results are obtained.
      Recoveries with the emulsion method ranged from 101 to 104%, with relative
      standard deviations of < or = 6%.

PMID- 12180696
TI  - Spectrophotometric determination of organic nitrogen by a modified Lassaigne
      method and its application to meat products and baby food.
AB  - A modified Lassaigne method was developed for N determination based on fusion of
      the organic substance with metallic Na, conversion of the cyanide in the aqueous
      leachate to thiocyanate by ammonium polysulfide treatment, and colorimetric
      measurement of the thiocyanate formed by the addition of excessive ferric ions in
      acidic medium. The mean molar absorptivity of the Fe(NCS)2+ complex at 480 nm is
      2.96 x 10(3) L/mol x cm, enabling quantitation of 0.25-7.72 ppm N (linear range)
      in the final solution. The relative amounts of Na, (NH4)2S2, and Fe(III) with
      respect to nitrogen in the analyte were optimized. The developed method was
      successfully applied to the determination of N in various brands of baby food,
      and it was compared statistically with the conventional Kjeldahl and elemental
      analysis methods. Protein nitrogen in a number of meat products was also
      precisely determined by the developed method. Thus, the total digestion time of
      the conventional Kjeldahl method was reduced considerably (e.g., to approximately
      15 min for a dried sample) with a relatively simple spectrophotometric method
      requiring no sophisticated instrumentation.

PMID- 12180697
TI  - Rapid detection of single cell bacteria as a novel approach in food microbiology.
AB  - Solid-phase cytometry (SPC) is a novel technique that allows rapid detection of
      bacteria at the single cell level, without the need for a growth phase. After
      filtration of the sample, the retained microorganisms are fluorescently labeled
      on the membrane filter and automatically counted by a laser scanning device. Each
      fluorescent spot can be visually inspected with an epifluorescence microscope
      connected to the ChemScan by a computer-driven moving stage. Depending on the
      fluorogenic labels used, information on the identity and the physiological status
      of the microorganisms can be obtained within a few hours. Although SPC was
      originally recommended for the determination of the total viable microbial count
      in water and other liquid samples, it may also be a promising technique for the
      detection and enumeration of bacteria in food samples, provided they can be
      isolated from the unfilterable matrix. The short detection time inherent in this
      approach is a considerable advantage over conventional plate counting, especially
      for slow-growing microorganisms. The basic principles of SPC are discussed as
      well as its potential for the detection of Mycobacterium paratuberculosis, a
      model example of a slow-growing bacterium in milk.

PMID- 12180699
TI  - Rapid methods for detection and enumeration of Campylobacter spp. in foods.
AB  - Campylobacter spp. are the most commonly reported bacterial cause of acute
      diarrheal disease in humans throughout the world. Traditional cultural methods
      for the detection and quantitation of Campylobacterspp. are slow and tedious;
      therefore, specific, sensitive, and rapid methods for campylobacters are needed
      to collect sufficient data for risk assessment and food safety policy
      development. We developed several rapid methods based on polymerase chain
      reaction (PCR), DNA hybridization, hydrophobic grid membrane filters (HGMFs), and
      enzyme immunoassays (EIAs). A PCR assay targeting C. jejuni, combined with a
      simple sample preparation procedure, detects as few as 0.3 most probable number
      (MPN)/mL C. jejuni in naturally contaminated chicken rinses after 20-24 h
      enrichment. An HGMF-EIA method using a commercial polyclonal antibody for
      Campylobacter detects and enumerates thermophilic Campylobacter spp. from spiked
      chicken rinse and milk, and naturally contaminated chicken rinses. A C. jejuni
      specific probe in an HGMF-DNA hybridization protocol specifically detects and
      quantitates C. jejuni in food samples. A dot-blot EIA combined with an MPN
      procedure quantitates thermophilic campylobacters from samples that might be
      difficult to filter through HGMFs.

PMID- 12180698
TI  - Molecular methods for identification and detection of bacterial food pathogens.
AB  - The polymerase chain reaction (PCR) shortens conventional microbiological methods
      for the detection of food pathogens either by replacing the conventional
      biochemical and serological identification or by its direct use on pre-enrichment
      media or food products. PCR allows fast and highly reliable identification of
      bacterial taxa, particularly phenotypically atypical bacterial strains. For
      reliablity, PCR primers and reaction conditions must be thoroughly optimized and
      evaluated, appropriate sample preparations must be developed, and a stringent
      laboratory protocol must be followed. Positive control systems are used to
      monitor possible inhibition of the reaction and negative controls are needed to
      monitor for contamination. The most recent developments involve messenger RNA
      based (mRNA-based) detection of viable bacterial pathogens and real-time PCR
      quantitation of pathogens.

PMID- 12180700
TI  - Detection of infectious salmon anaemia virus (ISAV) by in situ hybridisation.
AB  - An in situ hybridisation method was developed to detect infectious salmon anaemia
      virus (ISAV) in fixed tissues from Atlantic salmon Salmo salar L. Three DNA
      probes detected ISAV in heart, liver, kidney, spleen, caeca, and mid-gut from
      infected farmed Atlantic salmon obtained from a natural outbreak of ISA. The
      strongest signals were obtained using Probe S8, from Segment 8 of ISAV.
      Hybridisation was most prominent in the endothelial cells of heart tissue. The
      probes reacted specifically with ISAV; no hybridisation was evident in uninfected
      tissues from Atlantic salmon. Importantly, the probes did not cross react with
      the pathogens IHNV (haematopoietic necrosis virus), IPNV (infectious pancreatic
      necrosis virus), SPDV (salmon pancreas disease virus) and VHSV (viral
      haemorrhagic septicemia virus).

PMID- 12180701
TI  - Isolation and molecular characterization of herpesvirus from cultured European
      eels Anguilla anguilla in Taiwan.
AB  - A herpesvirus has been isolated for the first time from a population of European
      eels Anguilla anguilla cultured in a recirculated system in Taiwan. Syncytia
      formation was detected in EP-1 (eel epidermis) cell cultures inoculated with cell
      free homogenates prepared from both integument and visceral organs of moribund
      fish. Inoculation of homogenates onto EK (eel kidney) cell cultures induced giant
      cell formation. Subsequent passages produced a consistent and progressive
      cytopathic effect (CPE) in cell cultures. In this study, EP-1 cell cultures
      infected with EEHV (European eel herpesvirus) were examined using an electron
      microscope. Numerous nucleocapsids of about 100 nm in diameter were found within
      the nucleus of infected cells, whereas enveloped particles were observed within
      the cytoplasm. The mature viral particle, about 235 nm in diameter, had an
      electron-dense core with a hexagonal nucleocapsid surrounded by a coarse capsule.
      Histopathological examination of moribund fish showed epithelial hyperplasia with
      intracytoplasmic metabolic inclusions in the skin. Macrophage aggregates were
      found in liver, spleen, and kidney. A pair of primers designed from channel
      catfish virus and salmonid herpesvirus 1 was used in a polymerase chain reaction.
      A 402 bp fragment was amplified and cloned from genomic DNA of EEHV. The
      nucleotide homology was 99% (298 of 300) with DNA polymerase of eel herpesvirus
      (anguillid herpesvirus). EEHV nucleic acids were detected within
      melanomacrophages in the skin, liver, spleen and kidney by in situ hybridization
      (ISH).

PMID- 12180702
TI  - Assessment of genetic variability and relatedness among atypical Aeromonas
      salmonicida from marine fishes, using AFLP-fingerprinting.
AB  - Atypical strains of Aeromonas salmonicida are the causal agent of atypical
      furunculosis or ulcer disease in various fish species, including spotted wolffish
      Anarhichas minor, which is a promising species in the Norwegian fish-farming
      industry. Isolates of atypical A. salmonicida comprise a very heterogenous group
      showing large variety in biochemical, molecular and virulence characteristics.
      The genetic variability among atypical isolates from wolffish was characterised
      using amplified fragment length polymorphism analysis: AFLP-fingerprinting.
      Additional isolates from halibut Hippoglossus hippoglossus, turbot Scophthalmus
      maximus, cod Gadus morhua and several salmonid fishes were included for
      assessment of variability and relatedness among a total of 56 atypical isolates
      of A. salmonicida. They were compared to reference strains of A. salmonicida
      subspecies and to other Aeromonas species pathogenic in fishes. AFLP-fingerprints
      subjected to similarity analysis yielded a grouping of the isolates into several
      clusters, revealing genetic heterogeneity among the isolates. There seems to be a
      correlation between genetic similarity among isolates and the fish host. The
      Icelandic isolates, mainly from cod, formed a very homogeneous subcluster, which
      was closely related to the wolffish isolates. All atypical isolates from spotted
      and common wolffish grouped together in a large cluster and appear to be very
      homogeneous, even though they had been isolated over a period of 8 yr at
      different locations in Norway. On the other hand, most of the isolates from
      turbot and halibut grouped together into 2 different clusters, while the 9
      atypical isolates from salmonids appeared in 4 different clusters. Thus, the
      atypical isolates of A. salmonicida from halibut, turbot and salmonid fishes seem
      to be more genetically diverse than those from wolffish and cod.

PMID- 12180704
TI  - Prokaryote infections in the New Zealand scallops Pecten novaezelandiae and
      Chlamys delicatula.
AB  - Four intracellular prokaryotes are reported from the scallops Pecten
      novaezelandiae Reeve, 1853 and Chlamys delicatula Hutton, 1873. Elongated (1025 x
      110 nm), irregular (390 x 200 nm), or toroidal (410 x 200 nm) mollicute-like
      organisms (M-LOs) occurred free in the cytoplasm in the digestive diverticular
      epithelial cells of both scallop species. Those in P. novaezelandiae bore
      osmiophilic blebs that sometimes connected the organisms together, and some had a
      rod-like protrusion, both of which resemble the blebs and tip structures of
      pathogenic mycoplasmas. The M-LOs in C. delicatula had a slightly denser core
      than periphery. Round M-LOs, 335 x 170 nm, occurred free in the cytoplasm of
      agranular haemocytes in P. novaezelandiae, without apparent harm to the host
      cell. In P. novaezelandiae, 2 types of highly prevalent (95 to 100%) basophilic
      inclusions in the branchial epithelium contained Rickettsia-like organisms (R
      LOs). Type 1 inclusions occurred in moderately hypertrophied, intensely
      basophilic cells, 8 to 10 microm in diameter, containing elongate intracellular R
      LOs, 2000 x 500 nm. Type 2 inclusions were elongated and moderately basophilic in
      markedly hypertrophic branchial epithelial cells, 50 x 20 microm in diameter,
      containing intracellular organisms 500 x 200 nm in diameter. The possible roles
      of these organisms in pathogenesis is discussed.

PMID- 12180703
TI  - Effects of a parasite-induced nephritis on osmoregulation in the common carp
      Cyprinus carpio.
AB  - Carp Cyprinus carpio infected with the haemoflagellate Trypanoplasma borreli
      undergo progressive nephritis associated with a destruction of approx. 40% of the
      nephric tubules. In an attempt to analyse the effect of the nephritis on the
      osmoregulation of affected carp, the clinical chemical properties of plasma and
      urine samples were analysed. Parasitised carp excreted greater amounts of
      electrolytes in their urine than uninfected carp which excreted highly diluted
      urine with an osmolality of about 10% of plasma osmolality. During the course of
      the infection, urine osmolality increased up to 26% of plasma osmolality by Day
      21 post-infection (p.i.). The plasma:urine ratio of Na+ also increased, while
      concomitant losses of Mg2+, Ca2+, K+ and inorganic phosphate were less
      pronounced. Infected carp were able to maintain a normal solute balance in their
      plasma. Plasma hydration (indicated by decreased protein contents) occurred on
      Day 21 p.i. Our data indicate that in T. borreli-infected carp, reabsorption
      processes of the distal renal tubule were disturbed, while secretory and
      absorption processes in the proximal tubule appeared to be less affected. In
      addition, infected carp were able to compensate their increased ion losses,
      probably by (energy-consuming) active absorption processes. The energy budget of
      infected carp was additionally affected by a substantial direct consumption of
      plasma glucose by the parasite.

PMID- 12180705
TI  - Evaluation of radiography, ultrasonography and endoscopy for detection of shell
      lesions in live abalone Haliotis iris (Mollusca: Gastropoda).
AB  - Radiography, ultrasonography and endoscopy were examined for their efficacy as
      non-destructive techniques for the detection of shell lesions in the marine
      gastropod Haliotis iris Gmelin. X-rays provided 69% correct diagnoses, with
      detection being restricted to those lesions which were mineralised. Ultrasound
      also showed potential to reliably detect lesions (83% correct diagnoses), but
      only where the lesions demonstrated a clear 3-dimensional relief. Lesion
      dimensions were underestimated using ultrasound. Endoscopy, applied to
      anaesthetised individuals, provided the most accurate method (92% correct
      diagnoses) for lesion detection and, although invasive, had no discernible effect
      on survival of the abalone 8 mo after screening.

PMID- 12180706
TI  - Cardiac abnormality with associated hernia in farmed rainbow trout Oncorhynchus
      mykiss.
AB  - A new type of cardiac malformation in rainbow trout Oncorhynchus mykiss from a
      broodstock fish farm is described. The ventricle of affected fish was located
      dorsodextrally to the atrium, while the latter was saccular, grossly enlarged and
      protruded through the muscles of the ventral body wall, forming a hernia covered
      only by dermis and epidermis. Histopathological changes included hypoplasia of
      the outer compact layer of the ventricular myocardium and severe distension of
      trabecular structures within the ventricle and atrium. Affected fish tolerated
      stress very poorly, and the majority of the affected fish died during the
      freshwater period. The causation(s) are not known, but hereditary and
      environmental factors are likely, as no infectious agents were isolated or
      detected microscopically.

PMID- 12180707
TI  - Effects of mercury on antioxidant mechanisms in the marine phanerogam Posidonia
      oceanica.
AB  - Biochemical markers of oxidative stress such as catalase activity, glutathione S
      transferase (GST) activity and levels of lipid peroxidation evaluated in terms of
      thiobarbituric acid reactive substances (TBARS) were measured in the sheaths of
      the marine phanerogam Posidonia oceanica (L.) Delile experimentally exposed to
      0.01, 0.1 and 1 microgHg l(-1) for 48 h. Up to a threshold concentration of 0.1
      microg Hg l(-1), an increase in catalase and GST activities and TBARS levels was
      observed, indicating that the antioxidant mechanisms were overtaxed and could not
      prevent membrane lipid peroxidation. Paradoxically, at 1 microg Hg l(-1), the
      damage seemed to decrease, as the lipid peroxidation levels of exposed sheaths
      were lower than those of controls and as catalase and GST activities were not
      different from those of controls. A possible rapid induction of phytochelatins
      detoxifying mercury could occur at this high level of mercury.

PMID- 12180708
TI  - A parvo-like virus in cultured redclaw crayfish Cherax quadricarinatus from
      Queensland, Australia.
AB  - In the summer of 1999/2000, an epizootic occurred in cultured juvenile redclaw
      crayfish Cherax quadricarinatus on one commercial crayfish farm in northern
      Queensland, Australia. Mortalities occurred over 4 wk, with up to 96% cumulative
      mortalities in 2 earthen ponds stocked with juveniles. The crayfish were weak,
      anorexic and lethargic. A transmission trial was conducted, using filtered, cell
      free extract prepared from infected crayfish as inoculum. The disease was
      reproduced, with on-going mortalities occurring in inoculated crayfish over 55 d.
      Experimentally inoculated crayfish showed gross signs of malaise, anorexia and
      disorientation before dying. Two types of intranuclear inclusion bodies (INIBs)
      were seen in tissues of endodermal, ectodermal and mesodermal origin by light
      microscopy with haematoxylin and eosin (H&E) stained sections. 'Early'-stage
      INIBs were eosinophilic, rounded and located centrally within slightly enlarged
      nuclei while 'late'-stage INIBs were well-rounded and deeply basophilic. The
      gills, cuticular epithelium and epithelial cells of the foregut, midgut and
      hindgut were the most heavily infected tissues. By transmission electron
      microscopy, virions with an average diameter of 19.5 nm were seen within electron
      dense granular inclusion bodies within enlarged nuclei of both naturally and
      experimentally infected crayfish. The size of the virions and cytopathology are
      consistent with characteristics of viruses in the Family Parvoviridae. This is
      the first reported case of mass mortality caused by a parvo-like virus infection
      in C. quadricarinatus.

PMID- 12180709
TI  - Complete ORF1b-gene sequence indicates yellow head virus is an invertebrate
      nidovirus.
AB  - We report the sequence of an 8503 nucleotide (nt) region of the genome of yellow
      head virus (YHV) encompassing the open reading frame (ORF) 1b gene. Comparison
      with the sequence of Australian gill-associated virus (GAV) indicated that the
      region, comprising approximately 30% of the YHV genome, commences 268 nt upstream
      of the putative ORF1a termination codon and continues through ORF1b to a site 30
      nt downstream of the ORF2 initiation codon. YHV ORF1a and ORF1b overlap by 37 nt.
      MFOLD analysis of the overlap and downstream region predicted a 131 nt folding
      structure (deltaG = -47.3 kcal mol(-1)) with potential to form an RNA pseudoknot.
      The structure resides 3 nt downstream of a ribosomal frame-shift 'slippery'
      sequence (AAAUUUU) and a -1 frame-shift at this site would extend the ORF1
      polyprotein by 2616 amino acids (299322 Da). In ORF1b, YHV shares 88.9% amino
      acid sequence identity with GAV and includes conserved polymerase, metal ion
      binding, helicase and other domains (Motifs 1 and 3) characteristic of
      nidoviruses. Compared to GAV, the YHV non-coding region linking the ORF 1b and
      ORF2 genes contains a 263 nt insertion. However, the region contains a conserved
      core sequence of 46 nucleotides (84.8% identity) that includes a stretch of 20
      identical nucleotides surrounding a sub-genomic RNA transcription termination
      site. The data confirms the taxonomic placement of YHV in the Nidovirales and
      supports biological and topographical evidence that YHV and GAV may be classified
      as distinct species.

PMID- 12180710
TI  - Vertical transmission of gill-associated virus (GAV) in the black tiger prawn
      Penaeus monodon.
AB  - Chronic gill-associated virus (GAV) infection is endemic in Penaeus monodon
      broodstock captured from north-east Queensland in Australia and in farmed shrimp
      produced from these. We investigated the role of vertical transmission in
      perpetuating the high prevalence of these chronic GAV infections. Reverse
      transcription (RT)-nested PCR detected GAV in spermatophores and mature ovarian
      tissue from broodstock and in fertilized eggs and nauplii spawned from wild
      fertilized females. In laboratory-reared P. monodon (> 12 mo old) that had a high
      mortality rate, RT-nested PCR detected GAV in male spermatophores at levels
      significantly higher than that detected in the lymphoid organ. By transmission
      electron microscopy (TEM), GAV virions were detected in spermatophore seminal
      fluid, but not sperm cells. Histological evidence of hypertrophied cell foci
      (spheroids) and TEM observation of GAV nucleocapsids and virions in spheroid
      cells was also found in 100% of lymphoid organs of approximately 1.2 g juvenile
      P. monodon reared in the laboratory from postlarvae collected from commercial
      hatcheries. Sequence analysis of PCR amplicons from parental P. monodon and
      fertilized eggs of artificially inseminated broodstock indicated that GAV
      associated with eggs can originate from both the male and female parents.
      Although the female GAV genotype was predominant in eggs, there was some
      dependence on infection levels in the male and female shrimp as indicated by RT
      PCR. RT-nested PCR data on GAV levels in eggs, nauplii, protozoea and PL5 progeny
      of the artificial matings suggests that vertically transmitted virus is most
      probably associated with the egg surface.

PMID- 12180711
TI  - Another selective COX-2 inhibitor: more questions than answers?

PMID- 12180712
TI  - The concept of disease modification in spondyloarthropathy.

PMID- 12180713
TI  - Monitoring methotrexate hepatic toxicity in rheumatoid arthritis: is it time to
      update the guidelines?

PMID- 12180714
TI  - Not yet time to change the guidelines for monitoring methotrexate liver toxicity:
      they have served us well.

PMID- 12180715
TI  - Modifications in adenoviral coat fiber proteins and transcriptional regulatory
      sequences enhance transgene expression.
AB  - OBJECTIVE: To characterize the adenoviral properties required to enhance
      intracellular transgene expression for gene therapy. METHODS: Primary human
      fibroblasts and macrophages were infected with standard replication-defective
      adenoviruses, adenoviral vectors containing modified fiber coat proteins
      expressing Arg-Gly-Asp (RGD) or heparin sulfate binding moieties, or a
      tetracycline-regulatable transgene transcription system. Each of these vectors
      expressed the beta-galactosidase gene (beta-Gal), which was quantified by flow
      cytometry. Ankle joints from rats with adjuvant induced arthritis were transduced
      intraarticularly with each of the vectors and B-Gal expression was quantified by
      flow cytometry. RESULTS: Primary human fibroblasts and macrophages displayed
      marked increases in transgene expression from both modified fiber protein vectors
      and from the tetracycline-regulatable vector, compared to an unmodified vector
      expressing the transgene from the cytomegalovirus promoter/enhancer. In the rat
      model, the modified fiber protein vectors and the tetracycline-regulatable vector
      system also displayed increased transgene expression in inflamed rat joints.
      CONCLUSION: Adenovirus attachment and uptake by cells and promoter strength limit
      transgene expression from conventional adenoviral vectors in models of rheumatoid
      arthritis.

PMID- 12180716
TI  - Suppressive effect of hochu-ekki-to on collagen induced arthritis in DBA1J mice.
AB  - OBJECTIVE: To investigate the effect of hochu-ekki-to (HET) decoction on the
      development of collagen-induced arthritis (CIA) in mice. METHODS: CIA was induced
      in male DBA/IJ mice by immunization with 2 injections of bovine type II collagen
      (CII). HET was orally administered at different doses and with different
      schedules. The incidence of arthritis, arthritis index, levels of anti-CII
      antibody, interleukin 6 (IL-6), and tumor necrosis factor-alpha (TNF-alpha) and
      lymphocyte subsets were examined. RESULTS: HET caused suppression of CIA
      development in a dose dependent fashion and exerted a suppressive effect on CIA
      when administered from the first CII immunization or from the onset of CIA, but
      not when administered for 2 weeks before CII immunization. HET inhibited the
      production of specific anti-CII antibody, IL-6, and TNF-alpha, and tended to
      normalize the proportions of cells in lymphocyte subsets. CONCLUSION: HET
      suppresses the development of CIA, and HET redistributes the population of
      lymphocytes in lymph node and blood and inhibits IL-6 and TNF-alpha secretion in
      CIA mice.

PMID- 12180717
TI  - Antirheumatic effects of humanized anti-Fas monoclonal antibody in human
      rheumatoid arthritis/SCID mouse chimera.
AB  - OBJECTIVE: Anti-Fas monoclonal antibodies (Mab) are considered to be a potential
      therapeutic agent for rheumatoid arthritis (RA). However, Fas mediated liver and
      chondrocyte damage is a serious problem in its clinical application. m-HFE7A, a
      novel anti-Fas Mab, selectively induces apoptosis in inflammatory cells. We
      succeeded in humanizing m-HFE7A to obtain h-HFE7A. We investigated the
      therapeutic effects of h-HFE7A Mab in RA. METHODS: We investigated the apoptosis
      inducing activities of h-HFE7A on human Fas ligand transfected cells and cultured
      human activated lymphocytes (human peripheral blood mononuclear cells and
      isolated human RA synovial lymphocytes), synoviocytes, and chondrocytes. We then
      examined the effects of h-HFE7A Mab in vivo using SCID-HuRAg mice implanted with
      human RA tissue. RESULTS: Administration of h-HFE7A Mab alone did not induce
      apoptosis in cultured human Fas ligand transfected cells and activated
      lymphocytes. However, apoptosis-inducing activities were noted by this Mab
      crosslinking with a secondary antibody or Fcgamma receptor positive cells. In
      contrast, no apoptosis induction by h-HFE7A was observed on cultured synoviocytes
      and chondrocytes with or without crosslinking. Thus the crosslinking with Fcgamma
      receptor positive cells is essential for the efficacy of this Mab in vivo. In the
      implanted tissue of the SCID-HuRAg mice, the number of inflammatory cells was
      significantly decreased in the h-HFE7A Mab treated group compared to the IgG
      treated control group. Moreover, there were only negligible effects in
      synoviocytes and chondrocytes with the h-HFE7A Mab. CONCLUSION: Administration of
      this novel humanized anti-Fas Mab may provide a new treatment for RA by inducing
      Fas mediated apoptosis in inflammatory cells.

PMID- 12180718
TI  - Hyperhomocysteinemia in rheumatoid arthritis: influence of methotrexate treatment
      and folic acid supplementation.
AB  - OBJECTIVE: To examine the effect of methotrexate (MTX) and folic acid
      supplementation on the homocysteine level in patients with rheumatoid arthritis
      (RA). METHODS: A cross sectional study was performed in 81 patients with RA,
      comprising a standardized clinical interview, an examination, and a blood
      specimen test. RESULTS: P-homocysteine tended to be lower in 41 patients
      receiving MTX, compared with 40 patients not receiving MTX. Of the MTX treated
      patients, 76% received folic acid supplementation. Multivariate analysis revealed
      a statistically significant association between P-homocysteine and P-creatinine
      (p < 0.001), and disease activity/progression measured by the Health Assessment
      Questionnaire score (p < 0.001). There was a tendency to negative association
      between P-homocys-teine and folic acid supplementation. CONCLUSION: P
      homocysteine in patients with RA receiving MTX and folic acid supplementation did
      not differ significantly from P-homocysteine in RA patients receiving other types
      of treatment.

PMID- 12180719
TI  - Cardiovascular risk factors in Chilean patients with rheumatoid arthritis.
AB  - OBJECTIVE: Epidemiologic studies have shown an increased mortality rate in
      patients with rheumatoid arthritis (RA). The most common cause of death in these
      patients is cardiovascular disease. We estimated the frequency of and examined
      risk factors for coronary artery disease in Chilean patients with RA. METHODS:
      Fifty-four patients with RA were studied: 87% were women, with a mean age (+/-
      standard deviation) of 51 +/- 13 yrs, 92% were rheumatoid factor positive, and
      51% had radiological erosions; 32 age and sex matched healthy controls were
      studied. Traditional cardiovascular risk factors and RA-specific variables were
      determined. Lipid profile, lipoprotein(a) [Lp(a)], homocysteine, ultrasensitive C
      reactive protein (CRP), anticardiolipin (aCL), anti-beta2-glycoprotein I (anti
      beta2-GPI) and antioxidized low density lipoprotein (ox-LDL) antibodies were
      measured. RESULTS: Median concentration of homocysteine was significantly higher
      in patients with RA than in controls: 10 (range 5.4-37.4) versus 8.3 (3.6-17.8)
      micromol/l (p = 0.001). Patients with RA who gave a history of cardiovascular
      disease had the highest concentrations of homocysteine: 15.1 (13.1-19.7) versus
      9.9 (5.4-37.4) micromol/l (p = 0.001). We found no differences between patients
      and controls in lipid profiles or Lp(a), or for other traditional risk factors.
      Anti-ox-LDL, IgG aCL, and IgG anti-beta2-GPI antibody levels were similar in both
      groups. IgM subtypes were higher in patients with RA than in controls, but in low
      titers. CONCLUSION: Our data suggest that a high homocysteine concentration could
      be an important risk marker for cardiovascular disease in patients with RA.

PMID- 12180720
TI  - A randomized, controlled, clinical trial of etoricoxib in the treatment of
      rheumatoid arthritis.
AB  - OBJECTIVE: To evaluate the efficacy and tolerability of the highly selective
      cyclooxygenase-2 (COX-2) inhibitor etoricoxib for the treatment of rheumatoid
      arthritis (RA). METHODS: A double blind, randomized, placebo and active
      comparator controlled, 12 week study conducted at 88 US sites. Eligible patients
      were chronic nonsteroidal antiinflammatory drug (NSAID) users with clinical
      worsening of RA upon withdrawal of prestudy NSAID. Patients received either
      placebo, etoricoxib 90 mg once daily, or naproxen 500 mg twice daily (2:2:1
      allocation ratio). Primary efficacy measures: patient and investigator global
      assessments of disease activity and direct assessment of arthritis by counts of
      tender and swollen joints. Key secondary measures: patient global assessment of
      pain, the Stanford Health Assessment Questionnaire, and the percentage of
      patients both completing the study and meeting the ACR20 criteria. Tolerability
      was assessed by tabulation of adverse events and routine laboratory evaluations.
      RESULTS: In all, 816 patients were randomized (placebo = 323, etoricoxib = 323,
      naproxen = 170), and 448 completed 12 weeks of treatment (placebo = 122,
      etoricoxib = 230, naproxen = 96). Compared with patients receiving placebo,
      patients receiving etoricoxib and naproxen showed significant improvements in all
      efficacy endpoints (p < 0.01). Compared with patients receiving naproxen,
      patients receiving etoricoxib demonstrated significant improvements (p < 0.05) on
      all primary endpoints and most other endpoints including ACR20 criteria. The
      percentage of patients who achieved an ACR20 response and who completed the study
      was 21%, 53%, and 39% in the placebo, etoricoxib and naproxen groups,
      respectively. Etoricoxib and naproxen were both generally well tolerated.
      CONCLUSION: In this study, etoricoxib 90 mg once daily was more effective than
      either placebo or naproxen 500 mg twice daily for treating patients with RA over
      12 weeks. Etoricoxib 90 mg was generally well tolerated in patients with RA.

PMID- 12180721
TI  - Effectiveness profiles and dose dependent retention of traditional disease
      modifying antirheumatic drugs for rheumatoid arthritis. An observational study.
AB  - OBJECTIVE: To determine the fate of traditional disease modifying antirheumatic
      drugs (DMARD) in the longer term, with special respect to dose related effects on
      drug retention rates, efficacy, and toxicity. METHODS: Historical analysis of
      DMARD therapies in 593 patients, comprising a total of 1319 courses of DMARD over
      a period of 2378 patient-years of therapy. DMARD dosages, treatment durations,
      and reasons for discontinuation, and measures of C-reactive protein and
      erythrocyte sedimentation rate were analyzed. Drug retention rates were estimated
      by Kaplan-Meier analysis. RESULTS: Methotrexate (MTX), chloroquine, and
      sulfasalazine (SSZ) emerged as the drugs most commonly applied during the past 15
      years, whereas gold salts and D-penicillamine became less frequently used during
      the past decade. Therapies had to be terminated mostly for adverse events (42%)
      or inefficacy (37%). Patients taking high dose therapy had significantly longer
      median retention rates than those taking low doses (SSZ 34 vs 7 mo; MTX 73 vs 39
      mo). Toxicity, ratherthan inefficacy, was the main reason for discontinuation of
      MTX and SSZ at low doses (p < 0.001). Median retention rates lasted < 24 mo for
      most DMARD, except for high dose MTX (> 36 mo). CONCLUSION: MTX, SSZ, and
      antimalarials have become the most commonly used traditional DMARD for rheumatoid
      arthritis. Their use is more often limited by toxicity than by inefficacy. If
      tolerated, they can be retained for long periods of time.

PMID- 12180722
TI  - Methotrexate, hydroxychloroquine, and intramuscular gold in rheumatoid arthritis:
      relative area under the curve effectiveness and sequence effects.
AB  - OBJECTIVE: The use of disease modifying antirheumatic drugs (DMARD) for
      rheumatoid arthritis (RA) is predicated on the expected value of the treatment
      course. Most clinical data are generalized from randomized controlled trials
      (RCT), which may result in estimates that are discordant with clinical experience
      and cannot address the effects of sequence of drugs. We computed estimates of
      relative DMARD effectiveness from a large observational database using area under
      the curve (AUC) data. METHODS: We examined data collected over a 20 year period
      on 1160 patients who were followed at the Wichita Arthritis Center. We utilized
      Health Assessment Questionnaire (HAQ) disability index data to quantify the
      effect of methotrexate (MTX), hydroxychloroquine (HCQ), and injectable gold
      (gold) on subsequent patient outcome. Using an AUC analysis, we compared length
      of treatment course, total disability averted, annual disability averted, and
      percentage of possible disability averted across drugs, and examined differences
      between first courses of therapy in DMARD naive patients and subsequent courses
      of the same and different DMARD in patients. RESULTS: Patients treated with MTX,
      HCQ, and gold improved at a rate of -0.33, -0.18 and -0.38 annualized HAQ area
      units, respectively. Since duration taking drug was greatest for MTX, then HCQ,
      then gold, the cumulative improvement was greatest with MTX (-1.07) versus gold (
      0.74) versus HCQ (-0.47) in disability unit years. All 3 drugs were better
      cumulatively with earlier disease (MTX-1.74 for < 1 yr vs -0.95 for > 1 yr; HCQ 
      0.68 vs -0.43; gold -1.71 vs -0.49). A second trial of the same drug was far less
      effective than the first course. On a percentage of possible improvement basis,
      these drugs were nearly equal since HCQ is given to less severely affected
      patients. CONCLUSION: MTX is the most effective DMARD of these 3 because of the
      length the therapeutic segment. In terms of disability averted, none of the
      agents decrease disability by more than 25% of the theoretically possible
      improvement. We documented that effectiveness of RA treatment is a function of
      drug sequence, duration of disease, whether it is a first or second course, and
      severity of disease. None of these clinically relevant observations have emerged
      from clinical trials. These methodologic approaches provide important
      quantitative comparative data and will be useful in further assessment of the
      relative effectiveness of present and future DMARD.

PMID- 12180723
TI  - Amelioration of accelerated collagen induced arthritis by a novel calcineurin
      inhibitor, ISA(TX)247.
AB  - OBJECTIVE: To examine the efficacy and toxicity of ISA(TX)247, a novel
      calcineurin inhibitor, in comparison to cyclosporine (cyclosporin A, CSA) and
      placebo in established collagen induced arthritis. ISA(TX)247 has up to 3-fold
      greater potency than CSA in an in vitro whole blood calcineurin inhibition assay
      and in in vivo solid organ and cell transplantation models. Phase I clinical
      trials show no discernible nephrotoxicity. METHODS: Type II collagen immunized
      DBA/Lac J mice with established arthritis were randomized to treatment with
      ISA(TX)247 (125/250/500 microg/mouse), CSA (250/500 microg/mouse), or drug
      vehicle, by daily intraperitoneal injection for 10 days from the onset of
      clinical arthritis. RESULTS: A significant dose dependent reduction in clinical
      severity was observed in ISA(TX)247 treated but not in CSA treated animals 10
      days after the onset of established arthritis, and when examined by area under
      the curve analysis during the treatment period. Significant improvement in paw
      swelling (p < 0.001), synovial histology (p < 0.001), and articular cartilage
      damage scores (p = 0.002) was also noted in ISA(TX)247 treated animals, even in
      the 125 pg dose group (p = 0.03 for paw swelling and synovial histology). By
      comparison, CSA had no significant effect on either synovial inflammation or
      articular cartilage damage. ISA(TX)247 (500 microg dose group) was the only
      treatment to significantly decrease the development of proximal interphalangeal
      joint erosions (p < 0.05). A significant reduction in Type II collagen antibody
      titer was noted in ISA(TX)247 animals in both 250 microg (p = 0.02) and 500
      microg (p = 0.004) dosage groups, but only in the 500 microg group for CSA (p =
      0.004). Treatment was well tolerated, with no significant toxicity in ISA(TX)247
      groups. CONCLUSION: ISA(TX)247 demonstrates efficacy and safety in the treatment
      of established collagen induced arthritis. Together with its improved potency and
      nephrotoxicity profile in comparison to CSA, this agent warrants further clinical
      investigation in autoimmune disease. Phase II studies in rheumatoid arthritis
      have been initiated.

PMID- 12180724
TI  - High dose chemotherapy and hematopoietic stem cell transplantation: a study of
      treatment preference in patients with rheumatoid arthritis and rheumatologists.
AB  - OBJECTIVE: Patients with intractable rheumatoid arthritis (RA) may benefit from
      treatment with high dose chemotherapy followed by rescue with autologous
      hematopoietic peripheral blood stem cell transplant (HSCT). We investigated
      whether the risks of this approach are acceptable to patients with RA and
      rheumatologists and whether risk taking by patients was associated with disease
      characteristics, socioeconomic variables, and/or personality traits. METHODS: A
      survey in the outpatient clinic was conducted among 2 cohorts of 45 (cohort A)
      and 51 (cohort B) RA patients with active disease. Patients received information
      about the potential benefit of HSCT (2/3 chance of a good clinical response, 1/3
      no response) and treatment related morbidity and mortality. Cure was assumed not
      to be a realistic perspective. Cohort A was asked to choose between their own
      disease state for an indefinite time or HSCT. Nonparametric tests were performed
      to evaluate putative predictive factors that led patients to accept transplant
      related mortality (TRM): swollen joint count, tender joint count, visual analog
      scale (VAS) measures of disease activity and pain, erythrocyte sedimentation
      rate, Health Assessment Questionnaire (HAQ), socioeconomic variables, RA Quality
      of Life Questionnaire (RAQoL), and the Life Orientation Test. Cohort B was asked
      to consider a worst case scenario with respect to their disease activity. The
      minimal duration of benefit was assessed, given a TRM of 0.01% and 2%. To
      evaluate treatment preference of physicians, 96 Dutch rheumatologists responded
      to a hypothetical clinical case analogous to the interviews with RA patients. The
      minimum duration of benefit was assessed, given a TRM of 2% and the maximal TRM
      acceptable to rheumatologists if duration of benefit was 2 years in 2/3 patients.
      RESULTS: In cohort A, 5 of 45 patients were willing to accept risk of death. VAS
      disease activity (p = 0.006), VAS pain (p = 0.021), and HAQ (p = 0.05) were
      significantly higher in patients willing to accept risk of death. Religiosity (p
      = 0.093), a higher Ritchie Articular Index (p = 0.096), and low quality of life
      (by RAQoL) (p = 0.133) showed trends toward risk taking. In cohort B, 22 of 50
      patients (44%) were willing to accept a risk of TRM related to HSCT. For the 22
      patients the median required duration of benefit given a TRM of 2% was 5 years
      (range 1-15). Physicians also required a median duration of benefit of 5 years.
      CONCLUSION: We evaluated risk taking in patients with RA and physicians based on
      a realistic perspective in which the tradeoff between short term risks and
      possible longterm benefit of HSCT was investigated. Based on current efficacy
      data for HSCT (2 years improvement in 2/3 patients), half the patients would
      accept the current TRM of 2%, based on registry results. Patients willing to
      accept TRM had higher VAS disease activity, VAS pain, and HAQ. Doctors were more
      willing to accept mortality in the treatment of RA.

PMID- 12180725
TI  - Infusion of epinephrine decreases serum levels of cortisol and 17
      hydroxyprogesterone in patients with rheumatoid arthritis.
AB  - OBJECTIVE: To investigate the pituitary and adrenal hormone response after an
      intravenous epinephrine challenge in patients with rheumatoid arthritis (RA) and
      controls. METHODS: Fifteen untreated female patients with RA (age 51.5 +/- 3.2
      yrs) and 7 healthy female controls (48.0 +/- 4.3 yrs) were infused with
      epinephrine (0.05 microg/kg/min) for about 20 min. Plasma levels of
      adrenocorticotropic hormone (ACTH), and serum levels of cortisol, 17
      hydroxyprogesterone (17OHP), and dehydroepiandrosterone sulfate (DHEAS) were
      analyzed at baseline and shortly after cessation of epinephrine infusion (20
      min). RESULTS: At baseline and after epinephrine infusion, serum levels of
      cortisol (p = 0.045) and 17OHP (p = 0.021) were higher in controls compared to
      patients with RA. In contrast, at baseline and after epinephrine infusion, plasma
      levels of ACTH and serum levels of DHEAS were similar in controls and patients.
      After epinephrine infusion, only the patients with RA had a significant decrease
      of serum cortisol (p = 0.026) and serum 17OHP (p = 0.026). Plasma levels of ACTH
      (p = 0.073) and serum levels of DHEAS (p = 0.055) tended to decrease. CONCLUSION:
      Serum cortisol and 17OHP (cortisol precursor) were lower in patients with RA
      compared to controls despite similar ACTH levels. Simulation of an
      adrenomedullary stress response by epinephrine infusion decreased serum cortisol
      and 17OHP in patients but not in controls. Such a response may play an
      unfavorable role during a typical stress reaction in patients with RA that may
      lead to a more proinflammatory situation.

PMID- 12180726
TI  - Screening for hydroxychloroquine toxicity by Texas ophthalmologists.
AB  - OBJECTIVE: To determine current practice patterns for screening for
      hydroxychloroquine (HCQ) toxicity by Texas ophthalmologists. METHODS: A survey
      was sent to all comprehensive ophthalmologists and retina specialists in the
      state of Texas. Questions included need for baseline examinations, frequency of
      followup, tests used to monitor for toxicity, and influences on monitoring
      regimen. RESULTS: Two hundred ninety of 577 surveys were returned correctly
      completed (response rate = 50.3%). Two hundred fifty-seven respondents (88.6%)
      felt a baseline examination was necessary prior to beginning HCQ therapy, and 223
      (76.9%) followed patients every 6 months during HCQ therapy. Visual acuity, slit
      lamp examination, and dilated fundus examination were performed on almost all
      patients, and about three-quarters of respondents also checked visual fields and
      color vision. While 183 ophthalmologists (63.1%) used the Ishihara
      pseudoisochromatic plates to check color vision, there was no consensus on the
      preferred visual field test. One hundred twenty-two respondents (42.1%) stated
      they had diagnosed a patient with HCQ ocular toxicity. CONCLUSION: Most
      ophthalmologists in Texas continue to perform baseline examinations and follow
      HCQ patients semiannually for the development of ocular toxicity despite recent
      recommendations questioning the need for such close followup. The majority check
      visual acuity, perform slit lamp and dilated fundus examinations, and test color
      vision and visual fields, although there is no consensus on the preferred method
      to test visual fields.

PMID- 12180727
TI  - Macrophage migration inhibitory factor gene polymorphism is associated with
      sarcoidosis in biopsy proven erythema nodosum.
AB  - OBJECTIVE: To assess whether polymorphism of the macrophage migration inhibitory
      factor (MIF) gene at the position -173 is implicated in the development of
      sarcoidosis. METHODS: Twenty-eight patients with biopsy proven erythema nodosum
      (EN) associated with sarcoidosis, 70 patients with biopsy proven EN related to
      other etiologies, and 122 healthy matched controls from the Lugo region of
      Northwest Spain were studied. Patients and controls were genotyped for a single
      nucleotide polymorphism in the 5'-flanking region at position -173 of the MIF
      gene, using SNapshot ddNTP primer extension, followed by capillary
      electrophoresis (ABI 3100). RESULTS: A significantly increased frequency of the C
      mutant allele was observed in patients with EN secondary to sarcoidosis compared
      to controls (p = 0.0016; p(corr) = 0.0032; OR 2.78, 95% CI 1.45, 5.35) and also
      compared to patients with EN unrelated to sarcoidosis (p = 0.0004; p(corr) =
      0.0008; OR 3.72, 95% CI 1.75, 7.87). Patients with EN carrying an MIF 173 C
      allele were found to have an increased risk of sarcoidosis (57% in EN secondary
      to sarcoidosis vs 24% in patients with EN related to other etiologies; p = 0.002;
      p(corr) = 0.004; OR 4.16, 95% CI 1.64, 10.50). CONCLUSION: This is the first
      attempt to assess the influence of MIF genetic polymorphism at position -173 in
      the development of sarcoidosis. The MIF 173 C allele is associated with a
      significantly increased risk of developing sarcoidosis in patients with EN.

PMID- 12180728
TI  - Systemic lupus erythematosus disease severity in men and women: a case-control
      study.
AB  - OBJECTIVE: To assess the severity of systemic lupus erythematosus (SLE) in men
      compared to women. METHODS: A validated Lupus Severity of Disease Index (SDI) was
      used to assess disease severity in a retrospective multicenter case-control
      study. Each man (n = 18) was matched with 1-3 women (n = 36) for age, disease
      duration, and clinical setting. Clinical and serologic features were assessed and
      compared. RESULTS: There was no significant sex difference in disease severity
      (SDI 4.8 men vs 3.9 women). Comparison of other clinical or serologic
      manifestations showed that cerebritis, thromboembolic phenomena, and
      antiphospholipid antibodies were more common in men. CONCLUSION: There is no
      difference in lupus disease severity between men and women. However, there are
      sex-specific differences in expression of some disease manifestations.

PMID- 12180730
TI  - Factor V Leiden, prothrombin gene mutation, and thrombosis risk in patients with
      antiphospholipid antibodies.
AB  - OBJECTIVE: To determine if the prevalence of 2 prothrombotic genetic factors,
      factor V Leiden and prothrombin gene mutation, is increased in patients with
      antiphospholipid (aPL) antibodies with a history of venous/arterial thrombosis
      compared to patients with aPL antibodies with no history of thrombosis. METHODS:
      One hundred fifty-seven patients with aPL antibodies were studied. The occurrence
      of venous and arterial thrombotic events since the time of antibody detection was
      determined retrospectively, using appropriate clinical and diagnostic criteria.
      Clinical risk factors for thrombosis were documented and included hypertension,
      hyperlipidemia, cigarette smoking, diabetes, positive family history, use of oral
      contraceptive, pregnancy, trauma, hospitalization, varicose veins, and
      malignancy. Genomic DNA was extracted from blood cells for determination of
      factor V Leiden mutation G1691 --> A and prothrombin mutation G20210 --> A by
      polymerase chain reaction and restriction fragment length polymorphism analysis.
      RESULTS: Of 157 patients, 69 had a history of thrombosis (venous 37, arterial
      32); 147 (94%) patients had anticardiolipin (aCL) antibodies; 69 (45%) had lupus
      anticoagulant (LAC). The prevalence of factor V Leiden in patients with
      thrombosis was 13% compared to 4.6% in patients without thrombosis (OR 3.11, CI
      0.92-10.6). In patients with aCL antibodies, 15% of patients with arterial
      thrombosis had factor V mutation compared to 3.5% of patients without thrombosis
      (OR 4.9, CI 1.2-19.3). The prothrombin gene mutation was identified in 5
      patients, none of whom had thrombosis. Stepwise logistic regression analysis
      indicated that LAC (p = 0.005), male sex (p = 0.04), and hypertension (p = 0.03)
      were the strongest risk factors for developing thrombosis and that no additional
      risk was conferred by factor V Leiden (p = 0.13) and prothrombin gene mutation.
      CONCLUSION: Although the prevalence of factor V Leiden is modestly increased in
      patients with autoimmune aPL antibodies and thrombosis, these results suggest
      that its detection does not significantly increase the risk of a thrombotic
      event, once other clinical risk factors have been considered. Prothrombin gene
      mutation is not associated with thrombosis in patients with aPL antibodies.

PMID- 12180729
TI  - Role of DNA methylation in transcription of human endogenous retrovirus in the
      pathogenesis of systemic lupus erythematosus.
AB  - OBJECTIVE: We recently reported that transcription of human endogenous retrovirus
      (HERV) clone 4-1-like sequences is increased in patients with systemic lupus
      erythematosus (SLE). We therefore investigated the role of DNA methylation in the
      transcription of this HERV. METHODS: The effect of a demethylating agent, 5-aza
      deoxycytidine (5-aza C), on the transcription of HERV clone 4-1 in healthy
      individuals and patients with SLE was examined using reverse transcriptase-PCR
      and real-time quantitative PCR. RESULTS: 5-aza C increased clone 4-1-like
      messenger RNA in healthy controls, but not in patients with SLE. CONCLUSION:
      Defects of methylation may contribute to the transcription of HERV in patients
      with SLE and this may be related to the pathogenesis of SLE.

PMID- 12180731
TI  - Behcet's disease in southern Chinese patients.
AB  - OBJECTIVE: To describe the clinical characteristics of Behcet's disease (BD) in a
      southern Chinese population and compare them with those reported in other ethnic
      groups. METHODS: Patients with BD from 4 large regional hospitals in Hong Kong
      were identified from the hospital information retrieval system. Their records
      were retrospectively reviewed and the diagnosis was verified by at least 2
      rheumatologists using the International Study Group (ISG) criteria. Demographic
      data and various clinical features of our patients were collected and analyzed.
      RESULTS: Between 1978 and 2000, 37 adult patients with definite BD according to
      the ISG criteria were identified. All patients were ethnic southern Chinese.
      There were 19 women and 18 men (F:M = 1.1:1). The mean age at diagnosis was 36.2
      +/- 10 (18-74) years. Presenting features at diagnosis, in decreasing order of
      frequency, were oral ulceration (100%), genital ulceration (81%), skin lesions
      (73%), arthritis/arthralgia (54%), and ocular lesions (35%). Among skin lesions,
      the commonest manifestations were erythema nodosum (74%), folliculitis (44%), and
      acneiform nodules (30%). Arthritis was usually polyarticular (75%) and
      symmetrical, and involved the upper limb joints. Anterior uveitis was the most
      common ocular complication (77%) and was often bilateral. Involvement of other
      systems such as the central nervous system, gastrointestinal (GI) tract, and
      cardiopulmonary system was uncommon. Vascular complications were rare. Only 2
      (6%) patients had a positive pathergy test. Our patients were followed for a mean
      of 59.9 +/- 52 months. Apart from recurrent attacks of orogenital ulceration and
      uveitis, new systemic features were unusual. One patient died of bowel
      perforation as a result of active GI disease. Compared with other reported
      series, our patients had fewer ocular and systemic manifestations, and a
      significantly lower incidence of the pathergy reaction. CONCLUSIONS: BD is rare
      among southern Chinese in Hong Kong and tends to run a more benign course with
      less systemic involvement and fewer serious ocular complications. Whether the
      observed difference in clinical manifestations of the disease is related to a
      different HLA association or environmental factors warrants further studies.

PMID- 12180732
TI  - Trends in the incidence of polymyalgia rheumatica over a 30 year period in
      Olmsted County, Minnesota, USA.
AB  - OBJECTIVE: To determine time trends in the incidence and survival of polymyalgia
      rheumatica (PMR) over a 30 year period in Olmsted County, Minnesota, USA.
      METHODS: Using the unified medical record linkage system of the Rochester
      Epidemiology Project, we identified all incident cases of PMR among residents of
      Olmsted County, MN, between January 1, 1970, and December 31, 1999. Incidence
      rates were estimated and age- and sex-adjusted to the 1990 US white population.
      The annual incidence rates were graphically illustrated using a 3 year centered
      moving average. A Poisson regression model was used to evaluate predictors of PMR
      incidence. Survival rates were computed and compared with the expected rates in
      the population. RESULTS: There were 378 incident cases of PMR during the 30 year
      study period. Of these 66.6% were female and the mean age at incidence was 72.8
      years. The overall age and sex adjusted annual incidence of PMR per 100,000
      population aged > or = 50 years was 58.7 (95% CI 52.8,64.7). Incidence rates
      increased with age in both sexes, but in women, unlike in men, incidence fell
      after age 80. The incidence rates varied over the period of observation, but no
      significant trends over time were found. In the multivariable analysis, sex (p =
      0.023), age (p < 0.001), and age2 (p < 0.001), but not calendar year (p = 0.24)
      were significant predictors of incidence. Survival among individuals with PMR was
      not significantly different from that expected in the population (p = 0.06).
      CONCLUSION: The incidence of PMR has remained relatively stable over the past 30
      years.

PMID- 12180734
TI  - Cetylated fatty acids improve knee function in patients with osteoarthritis.
AB  - OBJECTIVE: To determine the benefit of cetylated fatty acids (CFA) on knee range
      of motion and function in patients with osteoarthritis (OA). METHODS: Sixty-four
      patients with chronic knee OA were evaluated at baseline and at 30 and 68 days
      after consuming either placebo (vegetable oil; n = 31) or CFA (Celadrin; n = 33).
      Evaluations included physician assessment, knee range of motion with goniometry,
      and the Lequesne Algofunctional Index (LAI). RESULTS: After 68 days, patients
      treated with CFA exhibited significant (p < 0.001) increase in knee flexion (10.1
      degrees) compared to patients given placebo (1.1 degrees). Neither group reported
      improvement in knee extension. Patient responses to the LAI indicated a
      significant (p < 0.001) shift towards functional improvement for the CFA group (
      5.4 points) after 68 days compared to a modest improvement in the placebo group (
      2.1 points). CONCLUSION: Compared to placebo, CFA provides an improvement in knee
      range of motion and overall function in patients with OA of the knee. CFA may be
      an alternative to the use of nonsteroidal antiinflammatory drugs for the
      treatment of OA.

PMID- 12180733
TI  - Myofibroblast accumulation correlates with the formation of fibrotic tissue in a
      rat air pouch model.
AB  - OBJECTIVE: The pathogenesis of arthritic joints involves cartilage degradation
      and pannus formation. It is well known that pannus influences the cartilage;
      however, the mechanism behind how the degrading cartilage interacts with pannus
      is not well known. To investigate this interplay, the expression of extracellular
      matrix (ECM) components in pannus and the degrading cartilage was analyzed.
      METHODS: Studies were performed using a rat air pouch model where cotton with
      viable or killed cartilage was implanted into 7-day-old pouches for 1-28 days.
      The remodeling of cartilage and the formation of tissue in the cotton was
      characterized histologically by quantitation of infiltrated cells. The amounts of
      collagen, hyaluronan, and proteoglycan were estimated. RESULTS: Implantation of
      homologous femoral head cartilage in cotton resulted in extensive remodeling of
      cartilage and formation of ECM in the cotton. In cotton without cartilage,
      fibroblasts and myofibroblasts were the predominant cells in the early stage of
      analyses. The ECM formed in cotton was of a fibrotic type, with mainly collagen
      and smaller amounts of proteoglycans correlating to the presence of
      myofibroblasts. In the cotton with cartilage, however, inflammatory cells such as
      neutrophils, macrophages, and lymphocytes dominated. Delayed accumulation of
      collagen and increased synthesis of proteoglycans occurred early in cotton with
      viable as well as non-viable cartilage. In later stages, the cell pattern changed
      and the myofibroblasts emerged together with an increasing collagen formation.
      CONCLUSION: The interaction between cartilage and the newly formed granulation
      tissue results in a faster degradation of cartilage molecules, which in turn leak
      into the surrounding ECM and affect the recruitment of myofibroblasts. This
      indicates the importance of the micromatrix.

PMID- 12180735
TI  - Joint space narrowing and relationship with symptoms and signs in adults
      consulting for hip pain in primary care.
AB  - OBJECTIVE: To study whether clinical symptoms and signs can predict radiological
      osteoarthritis (OA) of the hip in primary care patients with hip pain. METHODS:
      Consecutive patients (n = 220) aged 50 years or older consulting the general
      practitioner for hip pain and referred for radiological investigation underwent a
      standardized history, radiological, laboratory, and physical examination.
      Radiological OA was confirmed with joint space < or = 2.5 mm. Additionally, a
      more stringent definition was used (< or = 1.5 mm). The relationship between
      radiological OA and possible clinical symptoms/signs of OA was tested.
      Combinations of clinical symptoms/signs that had shown an independent
      relationship with radiological OA in multivariate analyses were tested for their
      predictive value. RESULTS: Radiological OA (joint space < or = 2.5 mm) of the
      (more) symptomatic hip was present in 35.5% of the study population and more
      severe OA (joint space < or = 1.5 mm) in 11.4%. Presence of 4 specific
      symptoms/signs from history and examination showed a positive predictive value
      (PPV) of 73% (specificity 91%, sensitivity 45%) for radiological OA. When 5
      specific symptoms/signs were present, the PPV for the more severe radiological OA
      was 82% (specificity 98%, sensitivity 72%), and when 6 or 7 specific
      symptoms/signs were present the PPV was 100% (specificity 100%, sensitivity 40%
      and 8%, respectively). Negative predictive values were high for almost all
      combinations. CONCLUSION: In primary care patients with hip pain, clinical
      symptoms and signs can to a moderate extent predict radiological OA and to a
      large extent more severe radiological OA.

PMID- 12180736
TI  - A cross sectional study of the association between sex, smoking, and other
      lifestyle factors and osteoarthritis of the hand.
AB  - OBJECTIVE: To describe the association between sex, smoking, physical activity,
      occupation, and previous digit fracture and hand osteoarthritis (OA). METHODS:
      Cross sectional study of 522 subjects from 101 Tasmanian families (348 women, 174
      men). Hand OA was assessed by 2 observers using the OARSI atlas for joint space
      narrowing and osteophytes at distal interphalangeal (DIP) and carpometacarpal
      joints as well as a score for Heberden's nodes based on hand photography. A
      structured questionnaire collected information regarding physical activity, sport
      participation, occupation, and smoking history. RESULTS: Women had a higher
      prevalence of hand OA and the increase with age was significantly higher for
      women at all sites (all p < 0.05). Ever smoking was associated with less frequent
      (OR 0.59, 95% CI 0.38, 0.92) and less severe Heberden's nodes (beta -0.60, 95% CI
      -1.03, -0.17), but not radiological disease. Recall of occupation, physical
      activity, and sport participation between the ages of 20 and 40 years had no
      association with the prevalence or severity of hand OA, while self-reported
      digital fracture was significantly associated with more common (OR 2.42, 95% CI
      1.22, 4.83) and severe DIP joint disease (beta +3.92, 95% CI +1.50, +6.36). No
      factors were associated with carpometacarpal disease. CONCLUSION: In this sample,
      women had a higher prevalence of hand OA at all sites as well as greater severity
      and a steeper age gradient (implying higher incidence rates). Smoking may
      decrease the risk of Heberden's nodes while having no effect on radiological hand
      OA, suggesting a differential effect possibly at the time of disease onset. With
      the exception of digital fracture, these data do not support a causal role for
      occupation or activity in earlier life with regard to hand OA.

PMID- 12180737
TI  - Interleukin 17 induced nitric oxide suppresses matrix synthesis and protects
      cartilage from matrix breakdown.
AB  - OBJECTIVE: To investigate the role of nitric oxide (NO) in basal and cytokine
      induced cartilage matrix breakdown and synthesis across different species and in
      chondrocytes cultured as isolated cells or as tissue explants. METHODS: Articular
      cartilage from bovine, porcine, or human joints was cultured as explants in serum
      free media. Explants or monolayer cultures of primary chondrocytes were treated
      with cytokines in the absence or presence of inhibitors [antibodies to leukemia
      inhibitory factor (anti-LIF) or tumor necrosis factor-alpha, dexamethasone, or
      inhibitors of aggrecanase or NO synthase]. NO production and matrix breakdown and
      synthesis were measured. RESULTS: At low concentrations, a novel interleukin 17
      (IL-17) family member induced matrix breakdown without altering NO production.
      Treatment of articular cartilage explants with dexamethasone or anti-LIF blocked
      NO production by IL-17, but not by IL-1alpha. Inhibition of NO production in
      cytokine treated cartilage explants enhanced matrix breakdown and partially
      overcame suppression of matrix synthesis. In isolated chondrocytes, inhibition of
      NO production decreased expression of gelatinase and increased expression of
      stromelysin. CONCLUSION: Endogenous NO serves a dual function in cartilage: to
      protect the tissue from matrix breakdown and to mediate suppression of
      proteoglycan synthesis by cytokines. Despite the similarities in biological
      function between IL-I and IL-17, their downstream signaling pathways are distinct
      and appear to be affected by extracellular matrix degradation.

PMID- 12180738
TI  - Therapeutic exercise for people with osteoarthritis of the hip or knee. A
      systematic review.
AB  - OBJECTIVE: To determine whether land based therapeutic exercise is beneficial for
      people with osteoarthritis (OA) of the hip or knee in terms of reduced joint
      pain, improved physical function, and/or the patient's global assessment of
      therapeutic effectiveness. METHODS: Five databases were searched for randomized
      clinical trials. Standardized mean differences (SMD) with their 95% confidence
      intervals (CI) were calculated for each study and then combined using a fixed
      effects model. RESULTS: Only 2 studies, totaling about 100 participants, could
      potentially provide data on people with hip OA. Fourteen studies provided data on
      1633 participants with knee OA. Nine of these studies were considered of high
      methodological quality. For pain, combining the results revealed a mean moderate
      beneficial effect (SMD 0.46, 95% Cl 0.35, 0.57), while for self-reported physical
      function a mean small beneficial effect (SMD 0.33, 95% CI 0.23, 0.43) was found.
      These results appeared to be sensitive to blinding of outcome assessor and choice
      of control group. CONCLUSION: Land based therapeutic exercise was shown to reduce
      pain and improve physical function for people with OA of the knee.

PMID- 12180739
TI  - Cartilage intermediate layer protein expression in calcium pyrophosphate
      dihydrate crystal deposition disease.
AB  - OBJECTIVE: To elucidate the mechanisms of calcium pyrophosphate dihydrate crystal
      deposition disease (CPPDCD) in the meniscus, synovium, labrum, tendon, ligament,
      and soft tissue, we studied the expression of cartilage intermediate layer
      protein (CILP). METHODS: Histological sections and clinical data from 33 patients
      who fulfilled the criteria of Ryan and McCarty for CPPD were reviewed. Formalin
      fixed and paraffin embedded tissue sections of 33 patients with CPPDCD were
      stained with hematoxylin and eosin (H&E) and alizarin red S. Immunostaining was
      performed using affinity purified polyclonal antibody to synthetic peptide
      corresponding to the N-terminal sequence of the 61 kDa domain of porcine CILP.
      RESULTS: The age of patients ranged from 49 to 89 years (median 73). The knee was
      the commonest site. Radiologically, almost all lesions exhibited fine,
      radiopaque, linear deposits in the meniscus, articular cartilage, and synovium or
      joint capsule. Histopathologically, all cases showed deposits of birefringent
      monoclinic or triclinic crystals, which were visualized by polarized light
      microscopy with a red analyzer filter. In alizarin red S staining, more numerous
      crystals were observed than in H&E staining. Crystal deposition was usually
      associated with adjacent variable amounts of hypertrophic and/or metaplastic
      chondrocytes in each type of tissue. Variable intensity of CILP immunostaining
      was found in deposits of each lesion. Hypertrophic/metaplastic chondrocytes in
      and around CPPD deposits were also positive for CILP. Small cartilaginous islands
      remote from the CPPD deposits exhibited a weak positivity for CILP. In addition,
      weakly positive chondrocytes were noted in a transitional zone between
      cartilaginous islands with and without the deposits. In addition to cytoplasmic
      immunoreactivity, immunostaining for CILP was observed in the pericellular
      fibrous matrix. CONCLUSION: Hypertrophic or metaplastic chondrocytes
      characteristic of CPPDCD may be directly involved in the formation of CPPD
      crystals. Our study suggests that increased CILP expression was closely
      associated with CPPDCD, and might play a role in promoting CPPD crystal
      formation.

PMID- 12180740
TI  - Validation of the Arabic version of the WHO-ILAR COPCORD Core Questionnaire for
      community screening of rheumatic diseases in Kuwaitis. World Health Organization.
      International League Against Rheumatism. Community Oriented Program for the
      Control of Rheumatic Diseases.
AB  - OBJECTIVE: (1) To adapt the Community Oriented Program for the Control of
      Rheumatic Disease (COPCORD) Core Questionnaire (CCQ) for use as a rheumatic
      screening instrument among Kuwaitis, including translation, back translation,
      assessment of cross cultural equivalence, and reliability. (2) To determine the
      screening characteristics of the Arabic version of the CCQ for detecting
      rheumatic diseases compared to clinical examination by a rheumatologist. METHODS:
      Translation and assessment of cross cultural equivalence were undertaken using
      standard methods. Back translation was done by an Arabic-speaking rheumatologist.
      Interviewer agreement was assessed using a convenience sample. Sensitivity,
      specificity, and positive and negative predictive values were assessed first by
      administering the CCQ followed by full clinical examinations of a randomly
      selected sample of 359 Kuwaiti persons aged 15 years or older. RESULTS: (1) Cross
      cultural equivalence and back translation of the translated questionnaire were
      satisfactory. Interviewer agreement was acceptable. (2) The prevalence of
      rheumatic diseases based only on CCQ screening was 69% compared to 73% based on
      clinical examination. The sensitivity and specificity of the Arabic CCQ were
      94.4% and 97%, respectively, and the positive and negative predictive values of
      the instrument were 98.8% and 86.4%, respectively. CONCLUSION: The Arabic version
      of the CCQ appears promising as a screening tool to detect rheumatic diseases in
      Arabic speaking communities. The findings suggest that the Arabic CCQ followed by
      clinical examinations in positive respondents can provide an acceptable estimate
      of prevalence of rheumatic diseases. We intend to use this instrument to screen
      for the prevalence of rheumatic diseases among Kuwaiti nationals.

PMID- 12180741
TI  - Physically demanding situations as predictors of disability pensioning with soft
      tissue rheumatism among persons 30-39 years old in Norway, 1981-90.
AB  - OBJECTIVE: Physically demanding work is a predictor of disability pensioning with
      musculoskeletal diseases. Being a parent is probably also physically demanding.
      Having manual work and being a parent will be analyzed as possible predictors of
      becoming a disability pensioner with soft tissue rheumatism (DPSTR) after
      controlling for level of education, employment, number of hours worked, income,
      age, sex, and marital status. METHODS: In this prospective study based on census
      data of persons 30-39 years old in 1980, predictors of becoming DPSTR during the
      followup period 1981-90 were identified by logistic regression analysis. RESULTS:
      Manual work was a predictor for becoming DPSTR for both men and women, while
      being a parent was neither a risk factor nor a protective factor for becoming
      DPSTR. Being employed was a predictor of becoming DPSTR for married women, but a
      protective factor for unmarried women and all men. Low level of education and
      being married or divorced were predictors of becoming DPSTR for both men and
      women. Working part time and having low income were predictors of becoming DPSTR
      among men. CONCLUSION: Physically demanding employment, but not a physically
      demanding private life, predicts becoming DPSTR. This may reflect that factors
      concerning a patient's private life are not taken into account when evaluating
      whether or not a disability pension should be granted, at least not for patients
      with uncertain medical conditions.

PMID- 12180742
TI  - Severe cardiac involvement in children with systemic sclerosis and myositis.
AB  - OBJECTIVE: To assess the outcome of children with systemic sclerosis (SSc) and
      features of polymyositis. METHODS: The charts of 4 children who met the American
      College of Rheumatology criteria for SSc and had features of polymyositis, as
      defined by the presence of proximal muscle weakness and elevated serum creatine
      phosphokinase or aldolase level, were retrospectively reviewed. RESULTS: All
      children had multivisceral involvement including (1) myocardial perfusion defects
      in all cases, with mild to severe dilated cardiomyopathy in 3; (2) lung
      restrictive syndrome in 3; (3) mild to severe esophageal involvement in all
      cases; and (4) severe intestinal dysfunction in one child. Combination therapy of
      corticosteroids, methotrexate (MTX), and cyclosporine resulted in improved skin
      thickness and muscle strength scores in all cases, as well as in lung restrictive
      syndrome in 2, but was not effective regarding the progression of intestinal
      malabsorption in one patient, esophageal dysmotility in 3 patients, and dilated
      cardiomyopathy in 3. Endstage cardiac failure caused 2 deaths. In one child,
      heart transplantation was performed for the first time in this indication.
      CONCLUSION: Children with diffuse cutaneous SSc and features of polymyositis are
      prone to develop severe cardiomyopathy. Combination therapy of corticosteroids,
      MTX, and cyclosporine seems to be active on muscle, skin, and lung involvement
      but does not impair progression of esophageal or myocardial dysfunction. Heart
      transplantation might be considered, as an experimental treatment, in young
      patients with severe cardiomyopathy and no other irreversible organ damage.

PMID- 12180743
TI  - Synovial membrane expression of matrix metalloproteinases and tissue inhibitor 1
      in juvenile idiopathic arthritides.
AB  - OBJECTIVE: Matrix metalloproteinases (MMP) are a large family of proteolytic
      enzymes involved in the remodeling of extracellular matrix during tissue
      resorption. We investigated synovial tissue expression of the main proteolytic
      enzymes (MMP-1, MMP-3, and MMP-13) and tissue inhibitor of metalloprotease 1
      (TIMP-1) in juvenile idiopathic arthritides (JIA). METHODS: Expression of MMP-1,
      MMP-3, MMP-13, and TIMP-1 was studied by immunohistochemical analysis of synovial
      tissues, obtained at synoviectomy or arthroplasty from 9 patients with JIA, and
      was correlated with mononuclear cell infiltration into the lining layer. RESULTS:
      MMP-1 and MMP-3 were abundantly expressed in the lining layer, showing a high
      degree of correlation with macrophage infiltration (CD68+ cells). MMP-13 showed a
      lower degree of expression, with tissue distribution almost restricted to the
      sublining regions. TIMP-1 tissue distribution was similar to that observed for
      MMP-1 and -3, although with a definitely lower number of positive cells.
      CONCLUSION: The expression of MMP-1 and MMP-3 in the synovium of patients with IA
      was clearly correlated with the degree of inflammation. This indicates the
      possible role of MMP in the pathogenesis of synovitis in this group of pediatric
      idiopathic arthritides. Inadequate expression of tissue inhibitors may represent
      a crucial event for the development and perpetuation of tissue damage.

PMID- 12180744
TI  - Juvenile onset ankylosing spondylitis (JAS) has less severe spinal disease course
      than adult onset ankylosing spondylitis (AAS): clinical comparison between JAS
      and AAS in Korea.
AB  - OBJECTIVE: To assess the frequency of juvenile onset ankylosing spondylitis (JAS)
      in Korean patients with AS and to differentiate the clinical characteristics of
      JAS from adult onset ankylosing spondylitis (AAS). METHODS: We studied 98
      consecutive patients with AS who visited the rheumatology clinic of a tertiary
      referral center and compared clinical and radiographic features of JAS (n = 41)
      with those of AAS (n = 57). RESULTS: Median age at onset in JAS was 14 years
      (range 7-16) and in AAS 22 years (range 17-38) (p < 0.01). Patients with JAS at
      presentation showed fewer spinal symptoms and more frequent peripheral joint
      symptoms than those with AAS (41.5% vs 80.7% and 73.2% vs 36.8%, respectively; p
      < 0.01). Current cervical spine disease was more frequent in AAS (66.7% vs 43.9%;
      p = 0.02) and current knee disease in JAS (26.8% vs 8.8%; p = 0.02). Patients
      with JAS showed a shorter tragus-wall distance (mean +/- SD 10.6 +/- 1.7 vs 13.1
      +/- 6.9 cm; p < 0.01), more mobility on the modified Schober test (5.7 +/- 2.0 vs
      4.0 +/- 2.6 cm; p < 0.01) and chest expansion (4.4 +/- 1.7 vs 3.2 +/- 1.8 cm; p <
      0.01), and a better forced vital capacity (75.1 +/- 14.1% vs 82.1 +/- 16.1% of
      predicted value; p = 0.03) than those with AAS. Totally ankylosed sacroiliitis
      and spinal syndesmophyte on radiographs were less frequent in JAS patients than
      in AAS (19.5% vs 47.4% and 17.1% vs 54.4%, respectively; p < 0.01). CONCLUSION:
      The frequency of JAS (41.3%) among Koreans was higher than that reported for
      Caucasians. General joint involvement pattern at disease onset in JAS was similar
      to previous reports. Our data suggest that clinically and radiographically JAS
      has a less severe spinal disease course than AAS.

PMID- 12180745
TI  - Changes in markers of bone turnover and inflammatory variables during alendronate
      therapy in pediatric patients with rheumatic diseases.
AB  - OBJECTIVE: Alendronate treatment for 12 months in pediatric patients with
      rheumatic diseases and secondary low bone mass was reported to result in a
      substantial increase in bone mineral density (BMD). In this study, we evaluated
      the changes in bone metabolism and disease activity markers in 45 patients ages 5
      to 18 years (31 female, 14 male) with rheumatic diseases treated with alendronate
      for 12 months. METHODS: Variables analyzed included demographic and
      anthropometric data, biochemical markers of bone metabolism, disease activity
      indexes, and BMD values. For all variables, the differences between levels at
      baseline and at 12 months were calculated; correlations between the variables and
      between the BMD variation over 12 months and baseline levels of the different
      variables were also evaluated. RESULTS: There was a statistically significant
      decrease of both bone resorption and bone formation markers over the 12 month
      treatment period. By contrast, no disease activity index changed significantly
      over one year. BMD Z score change over one year did not correlate with
      erythrocyte sedimentation rate, matrix metalloproteinase-3, interleukin 6, or C
      reactive protein variations over the same period. CONCLUSION: These results
      support the conclusion that alendronate treatment is accompanied by a reduction
      of bone turnover in pediatric patients and that the observed BMD increase is not
      secondary to a reduction of inflammatory activity.

PMID- 12180746
TI  - Gynecomastia and sexual impotence associated with methotrexate treatment.
AB  - Methotrexate (MTX) is the disease modifying antirheumatic drug most frequently
      used for rheumatoid and psoriatic arthritis (PsA). Several reports associate
      sexual dysfunction to MTX use. We describe 2 cases of sexual impotence and
      gynecomastia in patients with PsA treated with MTX. Although the mechanism
      underlying MTX induced sexual dysfunction is unknown, the potential consequences
      should be taken in account in view of the steady increase in the number of
      patients.

PMID- 12180747
TI  - Necrotizing granulomatous vasculitis associated with cocaine use.
AB  - Cocaine abuse may be associated with a destructive nasal and pharyngeal process
      felt to be due to ischemia secondary to vasoconstriction. This report is the
      first to document a necrotizing granulomatous vasculitis associated with nasal
      destruction and an oronasal fistula in a chronic cocaine user. Cocaine is an
      environmental insult that may play a role in triggering cerebral and non-cerebral
      vasculitis including a necrotizing granulomatous vasculitis of the respiratory
      tract.

PMID- 12180748
TI  - Subcutaneous tophaceous nodule formation due to deposition of cholesterol
      crystals.

PMID- 12180749
TI  - Identification of radiologic healing phenomena in patients with rheumatoid
      arthritis.

PMID- 12180750
TI  - Cauda equina syndrome or a complication of total hip arthroplasty?

PMID- 12180751
TI  - Coexistent sickle cell disease and juvenile rheumatoid arthritis: 2 cases with
      delayed diagnosis and severe destructive arthropathy.

PMID- 12180752
TI  - Basal levels of DHEAS as a marker for disease activity in premenopausal women
      with recent onset rheumatoid arthritis.

PMID- 12180753
TI  - Sjogren's syndrome associated T cell large granular lymphocyte leukemia: a
      possible common etiopathogenesis.

PMID- 12180754
TI  - Total plasma homocysteine is not increased in Japanese patients with gout.

PMID- 12180755
TI  - Alopecia areata in a patient with rheumatoid arthritis treated with leflunomide.

PMID- 12180756
TI  - Captopril induced lupus.

PMID- 12180758
TI  - Hemarthrosis and scurvy.

PMID- 12180757
TI  - Is fibrillin-1 the link between ankylosing spondylitis and Marfan's syndrome?

PMID- 12180759
TI  - Heritability of anthropometric phenotypes in caste populations of Visakhapatnam,
      India.
AB  - In this study, we used anthropometric data from six Andhra caste populations to
      examine heritability patterns of 23 anthropometric phenotypes (linear,
      craniofacial, and soft tissue measures) with special reference to caste
      differences. We obtained anthropometric data from 342 nuclear families from
      Brahmin, Reddy, Telaga, Nagara, Ag. Kshatriya, and Mala castes of Visakhapatnam,
      India. These caste groups represent the existing hierarchical stratification of
      Indian populations. We used a variance components approach to determine the
      heritability (h2) of these 23 anthropometric phenotypes (height, weight, BMI,
      etc.). The sample consisted of 1918 individuals ranging in age from 6 to 72 years
      (mean = 21.5, S.D. = 13.8). The heritabilities (h2 +/- S.E.) for all
      anthropometric traits for the entire sample were significant (p < 0.0001) and
      varied from 0.25 +/- 0.05 (BMI) to 0.61 +/- 0.05 (bizygomatic breadth) after
      accounting for sex, age, and caste effects. Since data on socioeconomic and
      nutritional covariates were available for a subset of families, we repeated the
      genetic analyses using this subset, which has yielded higher heritabilities
      ranging from 0.21 +/- 0.16 (head breadth) to 0.72 +/- 0.18 (nasal breadth). In
      general, craniofacial measurements exhibited higher h2 compared to linear
      measures. Breadth measurements and circumferences yielded more or less similar
      heritabilities. Age and sex effects were significant (p < 0.0001 ) for most of
      the traits, while the effects of caste, socioeconomic status, and nutritional
      status were inconsistent across the traits. In conclusion, anthropometric
      phenotypes examined in this study are under appreciable additive genetic
      influences.

PMID- 12180760
TI  - Genetic polymorphism study at four minisatellite loci (D1S80, D17S5, D19S20, and
      APOB) among five Indian population groups.
AB  - The present study reports the genetic variation observed among five
      anthropologically distinct population groups of India, using four highly
      polymorphic minisatellite loci (D1S80, D17S5, D19S20, and APOB 3' VNTR) in order
      to examine the effect of geographical and linguistic affiliations on the genetic
      affinities among these groups. Random individuals from five ethnic groups were
      studied; the sample size ranged from 235 to 364. The population groups belong to
      two geographically separated regions of India, the state of Maharashtra (western
      India) and the state of Kerala (southern India). The two Maharashtrian groups
      (Konkanastha Brahmins and Marathas) speak "Marathi," an Indo-European language,
      whereas the three Kerala population groups (Nairs, Ezhavas, and Muslims) speak
      "Malayalam," an Indo-Dravidian language. Genomic DNA was extracted from
      peripheral blood samples and analyzed using amplified fragment length
      polymorphism (Amp-FLP) technique. All four loci displayed high heterozygosity
      with average heterozygosity in the range of 0.82 to 0.84. The Polymorphic
      Information Content and Power of Discrimination were > or = 0.75 and > or = 0.80,
      respectively. The coefficient of gene differentiation was found to be low
      (average G(ST) = 1.2%; range between 0.6% at D1S80 locus to 1.6% at APOB 3' VNTR
      locus) across the loci, indicating close affinity among the population groups.
      The neighbor-joining tree revealed two clear clusters, one for the two
      Maharashtrian population groups and the other for the three Kerala population
      groups. The results obtained are in conformity with the geographical and
      linguistic backgrounds of the studied populations.

PMID- 12180761
TI  - Immunoglobulin allotypes among Taiwan aborigines: evidence of malarial selection
      could affect studies of population affinity.
AB  - The aborigines of Taiwan represent the indigenous inhabitants of the island at
      the time of the arrival of the Chinese from the mainland. Linguistically, the
      aboriginal Taiwanese are related to the Malayo-Polynesian-speaking inhabitants of
      Indonesia and the Philippines. Three tribes occupied lowland areas while six
      tribes occupied highland areas. Previous studies indicate that genetic markers
      associated with malaria occur in lowland populations. Though the GM haplotypes
      are demonstrated to be very useful in the measure of population affinities, the
      possibility of malarial selection on this locus could affect studies of
      population affinity. The present work is a case study to see whether a subdivided
      insular population under a possible selective load will provide divergent
      clustering analysis depending on the population sampled. Immunoglobulin allotype
      (GM and KM) profiles were generated on 230 lowland and 407 highland Taiwan
      Aborigines from the nine tribes. A highly significant difference in GM haplotype
      distribution was detected between lowland and highland populations (adjusted G =
      69.408, 2 df [degrees of freedom], p < 0.00001). There were no significant
      differences in KM*1 frequency by altitude. The Taiwan Aboriginal GM and KM
      frequencies were compared to data from Indonesians, Vietnamese, Thai, Malay,
      Chinese from Taiwan, and Ryukyu Islanders from Okinawa using cluster analysis.
      The lowland populations plot among the Thai (N, NC) and Malayan Aborigines. In
      contrast, the highland and total Taiwan Aborigine samples plot with the
      Indonesian, Vietnamese, and Malayan Negrito samples. Thus, depending on the
      populations of Taiwan Aborigines used, different conclusions could be reached.
      The highland population supports the published linguistic ties; however, the
      lowland population does not support the linguistic relationship with Indonesian
      populations but is more closely related to Thai and Malays, or reflects a similar
      selection history.

PMID- 12180762
TI  - Alleles and haplotypes of tumor necrosis factor (TNF) alpha and beta genes in
      three ethnic populations of Sulawesi Indonesia.
AB  - Polymorphic variation in two cytokine genes, tumor necrosis factor (TNF) -alpha
      and -beta, was examined in three ethnic groups, the Bugis, the Makassans, and the
      Torajans, who inhabit Sulawesi, a large island in the Indonesian archipelago, and
      formerly a Dutch colony. TNF-alpha and -beta are key molecules in immune
      responses to infection, and both have been implicated in the pathogenesis and
      clinical manifestations of parasitic diseases. Several polymorphic variants with
      the potential to affect cytokine levels in autoimmune diseases and parasitic and
      bacterial infection have been reported. Two loci in the promoter region of TNF
      alpha and two sites in the first intron of TNF-beta were scored in a maximum of
      150 Bugis, 168 Makassans, and 58 Torajans. Genotypes at the two TNF-alpha loci
      are not in Hardy-Weinberg equilibrium because of a deficit of heterozygotes (p <
      0.05). However, genotypes at the TNF-beta loci exhibit Hardy-Weinberg
      equilibrium. A comparison of allelic and genotypic frequencies at all TNF loci
      across the ethnic groups reveals that the differences are significant for
      TNFalpha(308) (p < 0.01) and for TNFbeta(NcoI) (p < 0.05). Overall, the
      distribution of the alleles differs from that seen in the few Asian populations
      for which data are available (p < 0.05). Construction of 4-locus haplotypes
      showed that, in addition to the five previously reported, four novel haplotypes
      were present in Sulawesi. These novel haplotypes were in low frequency, and two
      were seen only in Bugis (haplotypes F and J) and one (haplotype K) only in
      Makassans. The other, haplotype D, was present in Makassans and Torajans.
      Preliminary sampling of other ethnic groups suggests that three of these
      haplotypes (D, F, and J) may be restricted to Asian or Asian-derived populations.
      The frequency of the common TNF haplotypes differed between Dutch and Sulawesi
      populations, and these data also indicated that haplotype E, which has a
      relatively high frequency in the Dutch (25%), may be a useful marker of
      Dutch/European admixture in Indonesian populations, in which it is either rare
      (1%) or absent. The results suggest that unique allelic combinations with
      potential to influence cytokine secretion are present in Sulawesi, possibly as a
      consequence of parasite-driven selection, and argue for more extensive
      investigation of haplotype distribution in parasite-endemic areas.

PMID- 12180763
TI  - The peopling of Sao Tome (Gulf of Guinea): origins of slave settlers and
      admixture with the Portuguese.
AB  - The geographic origins of African slave settlers and the Portuguese genetic
      contribution to the population of Sao Tome (Gulf of Guinea) were assessed through
      the analysis of beta-globin haplotypes in 44 chromosomes bearing the betaS allele
      and through the study of the genetic variation in eight autosomal markers (APOA1,
      AT3, FY, LPL, OCA2, RB1, Sb19.3, and GC) informative for admixture in a sample of
      224 individuals. The observed betaS haplotype distribution (36.4% Bantu, 52.3%
      Benin, 4.5% Cameroon, 4.5% Senegal, and 2.3% atypical) is in accordance with the
      historical information on the major geographic sources of slave settlers of Sao
      Tome, although it captures a more important contribution of Central-West Africa
      regions than previously anticipated. European admixture, estimated to be 10.7 +/-
      0.9%, has created a considerable level of genetic structure, as indicated by the
      finding of significant linkage disequilibrium between 33% of unlinked marker loci
      pairs. Recent admixture was found to have an important contribution to these
      values, since removal of individuals with Portuguese or Cape Verdian parents or
      grandparents from the sample dropped the miscegenation level to 6.5 +/- 0.8% and
      reduced significant linkage disequilibrium to 11% of unlinked marker pairs. Taken
      together, these results indicate that the peopling of Sao Tome might have
      provided one of the first examples of the combination of diverse African
      contributions and European admixture that emerged from the overseas population
      relocations promoted by the Atlantic slave trade.

PMID- 12180764
TI  - Affinities among Melanesians, Micronesians, and Polynesians: a neutral biparental
      genetic perspective.
AB  - The human colonization of Remote Oceania, the vast Pacific region including
      Micronesia, Polynesia, and Melanesia beyond the northern Solomon Islands, ranks
      as one of the greatest achievements of prehistory. Many aspects of human
      diversity have been examined in an effort to reconstruct this late Holocene
      expansion. Archaeolinguistic analyses describe a rapid expansion of Austronesian
      speaking "Lapita people" from Taiwan out into the Pacific. Analyses of biological
      markers, however, indicate genetic contributions from Pleistocene-settled Near
      Oceania into Micronesia and Polynesia, and genetic continuity across Melanesia.
      Thus, conflicts between archaeolinguistic and biological patterns suggest either
      linguistic diffusion or gene flow across linguistic barriers throughout
      Melanesia. To evaluate these hypotheses and the general utility of linguistic
      patterns for conceptualizing Pacific prehistory, we analyzed 14 neutral,
      biparental genetic (short tandem repeat) loci from 965 individuals representing
      27 island Southeast Asian, Melanesian, Micronesian, and Polynesian populations.
      Population bottlenecks during the colonization of Remote Oceania are indicated by
      a statistically significant regression of loss of heterozygosity on migration
      distance from island Southeast Asia (r = 0.78, p < 0.001). Genetic and geographic
      distances were consistently correlated (r > 0.35, p < 0.006), indicating
      extensive gene flow primarily focused among neighboring populations. Significant
      correlations between linguistic and geographic patterns and between genetic and
      linguistic patterns depended upon the inclusion of Papuan speakers in the
      analyses. These results are consistent with an expansion of Austronesian-speaking
      populations out of island Southeast Asia and into Remote Oceania, followed by
      substantial gene flow from Near Oceanic populations. Although linguistic and
      genetic distinctions correspond at times, particularly between Western and
      Central-Eastern Micronesia, gene flow has reduced the utility of linguistic data
      within Melanesia. Overall, geographic proximity is a better predictor of
      biparental genetic relationships than linguistic affinities.

PMID- 12180765
TI  - Mitochondrial DNA diversity in Southeast Asian populations.
AB  - In a previous study of Southeast Asian genetic variation, we characterized
      mitochondrial DNAs (mtDNAs) from six populations through high-resolution
      restriction fragment length polymorphism (RFLP) analysis. Our analysis revealed
      that these Southeast Asian populations were genetically similar to each other,
      suggesting they had a common origin. However, other patterns of population
      associations also emerged. Haplotypes from a major founding haplogroup in Papua
      New Guinea were present in Malaysia; the Vietnamese and Malaysian aborigines
      (Orang Asli) had high frequencies of haplogroup F, which was also seen in most
      other Southeast Asian populations; and haplogroup B, defined by the Region V 9
      base-pair deletion, was present throughout the region. In addition, the Malaysian
      and Sabah (Borneo) aborigine populations exhibited a number of unique mtDNA
      clusters that were not observed in other populations. Unfortunately, it has been
      difficult to compare these patterns of genetic diversity with those shown in
      subsequent studies of mtDNA variation in Southeast Asian populations because the
      latter have typically sequenced the first hypervariable segment (HVS-I) of the
      control region (CR) sequencing rather than used RFLP haplotyping to characterize
      the mtDNAs present in them. For this reason, we sequenced the HVS-I of Southeast
      Asian mtDNAs that had previously been subjected to RFLP analysis, and compared
      the resulting data with published information from other Southeast Asian and
      Oceanic groups. Our findings reveal broad patterns of mtDNA haplogroup
      distribution in Southeast Asia that may reflect different population expansion
      events in this region over the past 50,000-5,000 years.

PMID- 12180766
TI  - A cautionary tale on ancient migration detection: mitochondrial DNA variation in
      Santa Cruz Islands, Solomon Islands.
AB  - Over the past decade, the origin of the first Malayo-Polynesian settlers of the
      island Pacific has become a contentious issue in molecular anthropology as well
      as in archaeology and historical linguistics. Whether the descendants of the
      ancestral Malayo-Polynesian speakers moved rapidly through Indonesia and Island
      Melanesia in a few hundred years, or whether they were the product of
      considerable intermingling within the more westerly part of the latter region, it
      is widely accepted that they were the first humans to colonize the distant
      Pacific islands beyond the central Solomon Islands approximately 3,000 years ago.
      The Santa Cruz Islands in the Eastern Solomons would have most likely been the
      first in Remote Oceania to be colonized by them. Archaeologically, the first
      Oceanic Austronesian settlement of this region appears to have been overlain by
      various later influences from groups farther west in a complex manner. Molecular
      anthropologists have tended to equate the spread of various Austronesian-speaking
      groups with a particular mitochondrial variant (a 9-base-pair [bp] deletion with
      specific D-loop variants). We have shown before that this is an oversimplified
      picture, and assumed that the Santa Cruz situation, with its series of
      intrusions, would be informative as to the power of mitochondrial DNA haplotype
      interpretations. In the Santa Cruz Islands, the 9-bp deletion is associated with
      a small number of very closely related hypervariable D-loop haplotypes resulting
      in a star-shaped Bandelt median network, suggesting a recent population
      expansion. This network is similar to Polynesian median networks. In a pairwise
      mismatch comparison, the Santa Cruz haplotypes have a bimodal distribution, with
      the first cluster being composed almost entirely of the 9-bp-deleted haplotypes
      again attesting to their recent origins. Conversely, the nondeleted haplogroups
      bear signatures of more ancient origins within the general region. Therefore,
      while the profiles of the two sets of haplotypes indicate very distinctive
      origins in different populations with divergent expansion histories, the sequence
      of their introduction into the Santa Cruz Islands clearly does not follow simply.

PMID- 12180767
TI  - JC virus genotypes in the western Pacific suggest Asian mainland relationships
      and virus association with early population movements.
AB  - Distinct genotypes of human polyomavirus JC (JCV) have remained population
      associated possibly from the time of dispersal of modern humans from Africa.
      Seven major genotypes with additional subtypes serve as plausible markers for
      following early and more recent human migrations in all parts of the world.
      Phylogenetic trees of JCV sequences from the major continental population groups
      show a trifurcation at the base indicating early division into European, African,
      and Asian branches. Here, we have explored JCV relationships in the island
      populations of the western Pacific. Since these islands were settled from the
      Asian mainland and islands of Southeast Asia, we expected that their virus
      genotypes might show an Asian connection. We found that Type 2E (Austronesian)
      and Type 8 (non-Austronesian) are widely distributed in western Pacific
      populations. A few south China strains were found (Type 7A). A subtype of Type 8,
      Type 8A, was confined to Papua New Guinea. In keeping with these assignments we
      find that phylogenetic analysis by neighbor-joining and maximum parsimony methods
      places Type 2E in a closer relationship to east Asian mainland strains such as
      Type 2A and Type 7. Our findings support the Asian origins of the western Pacific
      JCV strains, and suggest three broad movements: an ancient one characterized by
      Type 8A, and then Type 8B, followed much later by migrations carrying Type 2E,
      which may correlate with the arrival of Austronesian-language speakers, the
      bearers of the "Lapita" cultural complex (approximately 3,500 to 5,000 years
      ago), and relatively recent movements carrying largely Type 7A (south China)
      strains directly from the West.

PMID- 12180768
TI  - Something old, something new: do genetic studies of contemporary populations
      reliably represent prehistoric populations of Pacific Rattus exulans?
AB  - Through our research focusing on genetic studies of both ancient and extant
      commensal animals in the Pacific for addressing issues of population origins and
      mobility in the region, we have been able to process a large number of
      archaeological faunal remains that we can compare to modern samples from the same
      islands. These comparisons shed light on and provide specific evidence for Rattus
      exulans population change through time. This information may provide a model for
      understanding human populations in the region and will illustrate the
      complexities of using data obtained from modern populations to infer prehistoric
      relationships. Two case studies are presented here-analyses of modern and
      archaeological populations of R. exulans from both Chatham Island and New
      Zealand. These two cases provide very different pictures regarding the
      relationship between the archaeological and the extant populations.

PMID- 12180769
TI  - Thinking creatively: from nursing education to practice.
AB  - Creative thinking is a critical link in the teaching-learning process, one that
      enhances problem solving in nursing practice. This article describes a
      conceptualization of creativity based on focus groups with 12 post-RN students
      and two nurse educators. Inherent within the major theme, striving for balance,
      were three subthemes-enhancing self-esteem, working within structure, and making
      time for reflection (i.e., process). When participants achieved balance, both
      personally and professionally, they experienced increased creative energy that
      resulted in creative expression, subsequently displayed in educational endeavors
      and clinical practice (i.e., product). Strategies for fostering creativity and
      criteria for evaluating creativity are offered, and implications for nurse
      educators, managers, and practitioners are examined.

PMID- 12180770
TI  - Internal e-mail: an avenue of educational opportunity.
AB  - Internal e-mail systems offer an ideal opportunity to provide cost-effective,
      user-friendly educational experiences for employees. This article describes the
      use of computer technology to reach employees working different hours and in a
      variety of professional and nonprofessional roles. Monthly newsletters that
      provided contemporary, compressed, educational activities were created by the
      education department staff at a Veterans Affairs medical center. The educational
      sessions provided individualized, self-paced learning, supportive of the adult
      learner. Employees selected the educational activities that suited their needs.
      Although participation was optional, employees consistently took part in the
      activities.

PMID- 12180771
TI  - Recognizing the talent within: preparing clinicians for a role in professional
      development.
AB  - BACKGROUND: Ongoing professional development is recognized as crucial to the
      psychiatric and mental health nursing profession; however, implementing effective
      professional development programs has proved problematic. The Centre for
      Psychiatric Nursing Research and Practice in Victoria, Australia, developed a
      clinician-trainer course to overcome some of the identified problems. METHOD: An
      evaluation was conducted to measure participant satisfaction with the program.
      RESULTS: The initial evaluation suggests the course delivery and content were
      considered useful and relevant to participants, although areas for improvement
      were identified. CONCLUSION: The model developed is potentially effective but a
      longitudinal evaluation is required to determine the impact of the course on the
      implementation of professional development in the clinical domain.

PMID- 12180772
TI  - Meeting the continuing education needs of rural nurses in role transition.
AB  - BACKGROUND: The community health center (CHC) model of care delivery is gaining
      acceptance throughout Canada's newly created rural health regions. The resulting
      change in nursing functions presents a challenge to regional health authorities
      to ensure the attainment and maintenance of practice competencies. METHOD: This
      qualitative study examined strategies used in selected parts of Canada to prepare
      and support rural diploma-prepared nurses for role transition from acute care
      into CHCs. RESULTS: In light of CHC nurses' increased degree of autonomy, skill
      level, and focus on community wellness, the findings indicate a need for
      additional educational preparation and supportive strategies for transitioning
      nurses. CONCLUSION: Regions should educate the public and staff about the
      principles of primary health care, population health, and factors that determine
      health to help stakeholders understand their community, the current gaps in
      service delivery, and the role of CHC nurses. Key players at the provincial level
      should work together to address competency issues and continuing education needs
      of nurses in career transition.

PMID- 12180773
TI  - Effects of an educational bereavement program on health care professionals'
      perceptions of perinatal loss.
AB  - BACKGROUND: The purpose of this study was to examine the differences in health
      care professionals' perceptions of perinatal loss situations before and after an
      educational program on perinatal bereavement. METHOD: A quasi-experimental design
      was used in a pretest and posttest format. RESULTS: Scores were significantly
      higher (p = .000) on each of the posttest vignettes. Overall scores were lowest
      for the miscarriage pretest, whereas scores for the pretest vignettes for the
      stillbirth and neonatal loss were similar. A similar pattern occurred in the
      posttest vignette scores. CONCLUSION: Health care professionals' perceptions of
      the emotional care needs of families experiencing perinatal loss were
      significantly increased after an educational program. The miscarriage vignette
      had the largest change score and the lowest mean scores on the pretest and
      posttest, which indicates professionals do not view miscarriage as significant a
      loss as stillbirth and neonatal loss.

PMID- 12180774
TI  - Pain management: a practical approach to nursing education.
AB  - This article describes a program that provides a practical approach to educating
      staff nurses in pain management. The content is appropriate for adult patients
      across all clinical specialties. Pain assessment and commonly used analgesic and
      adjuvant medications are provided in nine educational sessions lasting 10 to 20
      minute. Each presentation topic is prepared in Microsoft Power Point in three
      versions: slides, notes, and handouts.

PMID- 12180775
TI  - Opalescent and cloudy fruit juices: formation and particle stability.
AB  - Cloudy fruit juices, particularly from tropical fruit, are becoming a fast
      growing part of the fruit juice sector. The classification of cloud as coarse and
      fine clouds by centrifugation and composition of cloud from apple, pineapple,
      orange, guava, and lemon juice are described. Fine particulate is shown to be the
      true stable cloud and to contain considerable protein, carbohydrate, and lipid
      components. Often, tannin is present as well. The fine cloud probably arises from
      cell membranes and appears not to be simply cell debris. Factors relating to the
      stability of fruit juice cloud, including particle sizes, size distribution, and
      density, are described and discussed. Factors promoting stable cloud in juice are
      presented.

PMID- 12180776
TI  - Some interrelated thermophysical properties of liquid water and ice. I. A user
      friendly modeling review for food high-pressure processing.
AB  - A bibliographic search yielded a set of empirical equations that constitute an
      easy method for the calculation of some thermophysical properties of both liquid
      water and ice I, properties that are involved in the modeling of thermal
      processes in the high-pressure domain, as required in the design of new high
      pressure food processes. These properties, closely interrelated in their physical
      derivation and experimental measurement, are specific volume, specific isobaric
      heat capacity, thermal expansion coefficient, and isothermal compressibility
      coefficient. Where no single equation was found, an alternative method for
      calculation is proposed. Keeping in mind the intended applications and
      considering the availability of both experimental data and empirical equations,
      the limits for the set of equations where set in -40 to 120 degrees C and 0 to
      500 MPa for liquid water and -30 to 0 degrees C and 0 to 210 MPa for ice I. The
      equations and methods selected for each property are described and their results
      analyzed. Their good agreement with many existing experimental data is discussed.
      In addition, the routines implemented for the calculation of these properties
      after the described equations are made available in the public domain.

PMID- 12180777
TI  - Whey components: millennia of evolution create functionalities for mammalian
      nutrition: what we know and what we may be overlooking.
AB  - Nutrition is undergoing a revolution owing to the recognition that some foods
      contain trophic, health-promoting factors distinct from essential nutrients. In
      this revolution, whey is increasingly being viewed as more than a source of
      proteins with a particularly nutritious composition of essential amino acids.
      Milk evolved under continuous Darwinian selection pressure to nourish mammalian
      neonates. Evolutionary pressure appears to have led to the elaboration of a
      complex food that contains proteins, peptides, complex lipids, and
      oligosaccharides that act as growth factors, toxin-binding factors, antimicrobial
      peptides, prebiotics, and immune regulatory factors within the mammalian
      intestine. Importantly, these trophic macromolecules are not essential, although
      the health benefits that their biological activities within the intestine provide
      likely contributed to neonatal survival. Human and bovine milks contain many
      homologous components, and bovine whey may prove to be a source for molecules
      capable of providing biological activities to humans when consumed as food
      ingredients. To approach this potential, food and nutrition research must move
      beyond the description of food ingredients as delivering only essential nutrients
      and develop a mechanistic understanding of the interactions between dietary
      components and the metabolic and physiological properties of the intestine.

PMID- 12180778
TI  - Toward sustainable production of protein-rich foods: appraisal of eight crops for
      Western Europe. Part I. Analysis of the primary links of the production chain.
AB  - Increased production of plant protein is required to support the production of
      protein-rich foods that can replace meat in the human diet to reduce the strain
      that intensive animal husbandry poses to the environment. The suitability of
      lupin (Lupinus spp.), pea (Pisum sativum), quinoa (Chenopodium quinoa Willd.),
      triticale (x Triticosecale), lucerne (Medicago sativa), grasses (Lolium and
      Festuca spp.), rapeseed/canola (Brassica napus), and potato (Solanum tuberosum)
      for protein production in Western Europe was studied on the basis of a chain
      approach. The aspects considered are the familiarity of farmers with the
      cultivation of the crop, prospects for rapid crop improvement, protein production
      (kg/ha), protein quality (absence of unwanted substances) and familiarity with
      the usage for human food in Western Europe. Pea, lucerne, and grasses are the
      most promising, fair prospects are foreseen for lupin, triticale, rapeseed, and
      potato, whereas the possibilities for quinoa are judged to lag far behind.
      Estimated protein production for pea, lucerne, and grasses is 1250, 2500, and
      2500 kg/ha, respectively.

PMID- 12180779
TI  - The precautionary principle and other non-tariff barriers to free and fair
      international food trade.
AB  - International food trade and world population are growing rapidly. National
      legislation has been enacted and implemented in many countries to assure good
      quality and safe foods to meet increased demand. No country is fully self
      sufficient in domestic food production to meet population demands, and all
      require some food imports. Current international food trade agreements call for
      free and fair food trade between all countries, developed and developing.
      National food legislation and food production, processing and marketing systems
      have evolved in most countries to ensure better quality and safer foods. At the
      international level the work of the FAO/ WHO Codex Alimentarius Commission
      (Codex) and the World Trade Organization Agreements on Sanitary and Phytosanitary
      Measures (SPS) and on Technical Barriers to Trade (TBT) and related Uruguay Round
      agreements have been agreed to by over 140 countries with the aim to promoting
      the free and fair trade of good quality and safe foods between all countries. The
      SPS and TBT agreements rely on science-based Codex standards, guidelines, and
      recommendations as benchmarks for judging international food trade disputes. A
      number of non-tariff barriers to trade, often related to agricultural subsidies
      and other food trade payments in developed countries, continue to give rise to
      complaints to WTO. They also continue to prevent free and fair trade,
      particularly for developing countries in international food trade. A number of
      these non-tariff barriers to trade are briefly examined, along with other
      domestic and international food trade problems, and recommendations for
      improvements are made.

PMID- 12180780
TI  - What limits genomics, proteomics, transcriptomics?

PMID- 12180781
TI  - Biodegradation and biological treatments of cellulose, hemicellulose and lignin:
      an overview.
AB  - In nature, cellulose, lignocellulose and lignin are major sources of plant
      biomass; therefore, their recycling is indispensable for the carbon cycle. Each
      polymer is degraded by a variety of microorganisms which produce a battery of
      enzymes that work synergically. In the near future, processes that use
      lignocellulolytic enzymes or are based on microorganisms could lead to new,
      environmentally friendly technologies. This study reviews recent advances in the
      various biological treatments that can turn these three lignicellulose
      biopolymers into alternative fuels. In addition, biotechnological innovations
      based on natural delignification and applied to pulp and paper manufacture are
      also outlined.

PMID- 12180782
TI  - Biology of killer yeasts.
AB  - Killer yeasts secrete proteinaceous killer toxins lethal to susceptible yeast
      strains. These toxins have no activity against microorganisms other than yeasts,
      and the killer strains are insensitive to their own toxins. Killer toxins differ
      between species or strains, showing diverse characteristics in terms of
      structural genes, molecular size, mature structure and immunity. The mechanisms
      of recognizing and killing sensitive cells differ for each toxin. Killer yeasts
      and their toxins have many potential applications in environmental, medical and
      industrial biotechnology. They are also suitable to study the mechanisms of
      protein processing and secretion, and toxin interaction with sensitive cells.
      This review focuses on the biological diversity of the killer toxins described up
      to now and their potential biotechnological applications.

PMID- 12180783
TI  - Bacterial membrane injuries induced by lactacin F and nisin.
AB  - The combined action of nisin and lactacin F, two bacteriocins produced by lactic
      acid bacteria, is additive. In this report, the basis of this effect is examined.
      Channels formed by lactacin F were studied by experiments using planar lipid
      bilayers, and bactericidal effects were analyzed by flow cytometry. Lactacin F
      produced pores with a conductance of 1 ns in black lipid bilayers in 1 mM KCI at
      10 mV at 20 degrees C. Pore formation was strongly dependent on voltage. Although
      lactacin F formed pores at very low potential (10 mV), the dependence was
      exponential above 40 mV. The injuries induced by nisin and lactacin F in the
      membranes of Lactobacillus helveticus produced different flow cytometric
      profiles. Probably, when both bacteriocins are present, each acts separately;
      their cooperation may be due to an increase in the number of single membrane
      injuries.

PMID- 12180784
TI  - Survival of several Rhizobium/Bradyrhizobium strains on different inoculant
      formulations and inoculated seeds.
AB  - The effect of a variety factors on the survival of several rhizobia strains on
      inoculants and inoculated seeds has been evaluated. Since the rhizobia strains
      showed different cell-density-evolution patterns on peat-based inoculants and on
      inoculated seeds, several inoculant formulations with highly effective
      Rhizobium/Bradyrhizobium strains (for Lupinus, Hedysarum, Phaseolus and Glycine
      max.) were monitored under the following storage conditions: (a) the inoculants
      were kept refrigerated (at 4 degrees C), or (b) at room temperature (25 degrees
      C). The effect of water content (30-50%, w/w) in the inoculants as well as that
      of several seed-coating adhesives were also investigated. Alternative carriers
      including perlite and vermiculite were tested. For all of the strains, survival
      on sterile peat-based inoculants was higher than on the corresponding unsterile
      peat formulation; for the latter, refrigerated storage conditions are recommended
      to ensure high bacterial densities. The water content of the inoculants had a
      differential effect on strain survival depending on the sterility of the peat,
      such that a high water content was more detrimental when unsterilized peat was
      employed. The best adherent for rhizobia survival was a gum arabic/water
      solution. Perlite was as effective as peat in maintaining a high population of
      rhizobia, at least for 6 months of storage.

PMID- 12180785
TI  - Vaginal microbiota in healthy pregnant women and prenatal screening of group B
      streptococci (GBS).
AB  - The microbiota of the lower female genital tract was evaluated from vaginal swabs
      obtained from 623 healthy pregnant women at gestation periods of 35-40 weeks.
      Isolated and identified microorganisms were expressed as percentages of total
      samples. As expected, lactobacilli made up the dominant vaginal microbiota (70%).
      Enterobacteriaceae, mainly Escherichia coli, Klebsiella spp. and Proteus, were
      present in 38% of the samples, which might reflect the possible contamination of
      vaginal tract with rectal microorganisms. Candida albicans was present in 10% of
      healthy pregnant woman assayed. Streptoccocci (Streptococcus sp. and Enterococcus
      faecalis with 3% and 4%, respectively) and other gram-positive cocci
      (Staphylococcus sp., 5%), along with other microorgansisms such as Gardnerella
      vaginalis (5%) and Pseudomonas aeruginosa (2%) may represent a potential
      infection risk. Streptococcus agalactiae (group B streptococci beta-hemolytic,
      GBS) was detected in 7% of the samples. GBS infection is a leading cause of
      neonatal morbidity and mortality in the developed world. Furthermore, GBS was
      often co-isolated with C. albicans (54.5%) in the samples. A complete and
      detailed evaluation of the vaginal biota swab, with particular attention to the
      presence of potential pathogens such as GBS, is a preventive strategy that can
      provide useful information to obstetricians and gynecologist in managing the last
      days of pregnancy and delivery.

PMID- 12180787
TI  - Science and culture.

PMID- 12180786
TI  - Identification and partial purification of K88ab Escherichia coli receptor
      proteins in porcine brush border membranes.
AB  - Six receptor proteins, with molecular masses ranging from 94 to 27 kDa, that bind
      to Escherichia coli K88ab fimbriae were recovered from brush border membranes and
      were detected after solubilization with Triton X-114. The recovery of these
      receptor proteins in the aqueous phase suggests their peripheral localization.
      The 63-, 60- and 33-kDa K88ab binding proteins were recovered using gel
      filtration chromatography of the aqueous phase.

PMID- 12180788
TI  - Molecular biology of blood pressure regulatory genes.
AB  - Blood pressure is determined by vascular resistance and circulating volume.
      Activation of vascular angiotensin II or thromboxane receptor is mostly involved
      in the former, and function of renal prostagalandin EP3 receptor or thiazide
      sensitive sodium-chloride co-transporter is also in the latter. We have cloned
      rat genes for these blood pressure regulatory factors, and studied their gene
      expression. Here we review the molecular biology of those genes, based on our
      observations.

PMID- 12180789
TI  - Effects of gender on stress ulcer formation in rats.
AB  - In the experimental stress literature, the results of investigations have not
      shown a specific sex-dependent vulnerability to stress ulceration. The aim of
      this study was to evaluate the importance of sex differences on stress ulcer
      development. Related to gender, the contributing factors for stress ulcer
      production such as luminal acidity, sialic acid as an marker of gastric mucosal
      protection, oxygen (O2)-derived free radicals and endogenous antioxidant defence
      mechanisms were also investigated. Fifty Wistar Albino rats weighing about 230 g
      and aged 7 or 8 months were divided equally into five groups: Group I normal male
      rats, group II castrated male rats, group III normal female rats in estrus phase,
      group IV normal female rats in diestrus phase and group V castrated female rats.
      Cold restraint model was used for 6 hours to produce stress ulcer. No
      statistically significant difference was found out between groups in view of
      gross and histopathologic damage. There was no significant difference between
      groups according to gastric luminal acidity, gastric mucosal sialic acid, gastric
      malonaldehyde (MDA) and catalase values. Gastric superoxide dismutase (SOD)
      activity was significantly lower in Group I in comparison to those of Group III
      and IV. Sex differences do not interfere stress ulcer formation. SOD activity in
      rat gastric tissue has varied significantly by hormonal milieu.

PMID- 12180791
TI  - An optimization method for reference dose point of rectum in brachytherapy of
      gynecological neoplasms.
AB  - Rectum reference dose points have a direct impact on the morbidity seen in
      gynecological intracavitaty radiotherapy. The aim of this study is to obtain less
      morbidity by marking rectum with radio opaque solution. Fourteen patients with
      gynecological cancer who underwent external radiotherapy received 15 Gray (Gy)
      intracavitary radiotherapy. During the internal radiotherapy planning, radio
      opaque solution has been administered into the rectum to observe it on lateral
      radiogram. Thus rectum reference dose point and five points were marked at sites
      nearest to the sources. Nucletron Planning system was used for obtaining three
      dimensional planning. After therapy patients were followed at every three months.
      Median follow-up was 18 months. Most frequently observed morbidities were grade 1
      2 rectitis and cystitis in six patients. As a result, more accurate rectum dose
      values and less factors causing dose changing can provide better results for
      gynecological intracavitary brachytherapy.

PMID- 12180790
TI  - Clinical value of color Doppler ultrasonography measurements of full-term
      newborns with perinatal asphyxia and hypoxic ischemic encephalopathy in the first
      12 hours of life and long-term prognosis.
AB  - The cerebral blood flow velocities (CBFV) of infants with perinatal asphyxia and
      hypoxic ischemic encephalopathy (HIE) in the first 12 hours of their lives have
      been the chief focus of our concern in this study. Cerebral ischemia which can
      develop in the earlier hours of HIE, and the detection and diagnosis of this
      condition with color Doppler ultrasonography (cD-USG) will be put into
      discussion. Twenty-three full-term newborn infants who had perinatal asphyxia and
      HIE together with a control group constituting twenty full-term newborn infants
      who produced no problems, were included in our study. All of the infants
      underwent cD-USG in the postpartum period of the first 12 hours (mean 8.4 hours).
      Measurements being based upon peak systolic velocity (PSV), end diastolic
      velocity (EDV) and Pouecelout's resistive index (RI) in anterior and middle
      cerebral arteries were conducted. The infants, having been discharged from the
      unit they were followed up for mean 9.8 months in the outpatient clinic. PSV and
      EDV counts in the postpartum first 12 hours of 23 infants who were detected to
      have HIE were found to be significantly lower compared to the control group,
      whereas RI counts were found to be significantly higher (p < 0.05). The counts
      obtained from the right and left cerebral arteries of the infants with HIE were
      found to be corraleted with each others. The neonates in the patient group were
      observed to have gone through this prognosis: Three of them died, three of them
      had cerebral palsy, one of them had infantile spasms, and three of them had
      developmental retardation. When we compared the CBFV of the 10 neonates who had
      poor prognosis, retrospectively with the other 13 neonates who had good
      prognosis, PSV and EDV were found to be significantly lower and RI significantly
      higher (p < 0.05). In the light of the data we have obtained, cD-USG can be
      considered to be a highly practical device in evaluating CBVF of the infants with
      HIE. A skillful detection of the decrease in cerebral blood flow which can
      develop in the postasphyxial first 12 hours and the prospective treatments being
      based upon this approach would contribute to the diagnosis, treatment and
      prognosis of such cases.

PMID- 12180792
TI  - A case of pseudoadenomatous hyperplasia of ciliary body epithelium successfully
      treated by local resection.
AB  - A case of pseudoadenomatous hyperplasia of ciliary body epithelium was reported
      in which malignant melanoma of ciliary body was suspected. Partial resection for
      histopathology was performed in conjunction with cataract extraction, anterior
      resection and photocoagulation. Histopathology of the tumor identified as
      pseudoadenomatous hyperplasia of ciliary body epithelium. Partial resection of
      ciliary body tumor may be an alternative method for its differential diagnosis
      rather than enucleation and iridocyclectomy.

PMID- 12180793
TI  - Nonsurgical treatment for odontogenic maxillary sinusitis using irrigation
      through the root canal: preliminary case report.
AB  - As a new nonsurgical treatment for odontogenic maxillary sinusitis (OMS),
      irrigation of the maxillary sinus through the root canal of the causal tooth was
      carried out to the patient with OMS that had proved refractory to conservative
      treatments (i.e., root-canal treatment of the causal tooth and antibiotic
      therapy). Clinical signs, symptoms, and radiographs before and after the new
      treatment revealed evidence of good healing. The clinical signs and symptoms,
      such as oppressive pain in the cheek and retrorhinorrhoea, entirely disappeared
      immediately after the irrigation (which was done only once) without pain, and the
      obstructed ostiomeatal unit was aerated on the follow-up CT images. There was no
      side effect associated with saline irrigation, nor any recurrence of symptoms
      since the irrigation. We therefore propose the irrigation through the root canal
      of the causal tooth as a new treatment for periapical disease-induced maxillary
      sinusitis, a technique that should ensure proper ventilation and drainage by
      relieving obstruction of the ostiomeatal unit.

PMID- 12180794
TI  - Primary cerebral neuroblastoma: a case report and review.
AB  - Primitive neuroepithelial tumors are the least common among supratentorial tumors
      in children. They pose great diagnostic difficulty, preoperatively as well as
      pathologically. Being quite rare, cerebral neuroblastomas are accepted as a
      distinct pathological entity, which differs from other neuroectodermal tumors,
      although clinically, radiologically, and morphologically at operation they are
      indistinguishable. Also differentiation between primary cerebral neuroblastoma
      and the other primitive neuroectodermal tumors may be difficult on light
      microscopy and be misleading. A 9-year-old girl with primary cerebral
      neuroblastoma who was initially misdiagnosed is reported. The other cases from
      the literature are reviewed and the nature of this rare tumor and its
      differential diagnosis is discussed.

PMID- 12180795
TI  - Lipid peroxidation and erythrocyte antioxidant enzymes in patients with Behcet's
      disease.
AB  - In spite of unknown etiology, it is now accepted that reactive oxygen species
      (ROS) produced by neutrophils may be related to the pathogenesis of Behcet's
      Disease (BD). The objective was to investigate whether increased production of
      ROS may affect erythrocyte oxidant/antioxidant system in patients with BD. The
      levels of malondialdehyde (MDA), one of the end products of lipid peroxidation,
      in plasma and erythrocyte, and the activities of superoxide dismutase (SOD) and
      glutathione peroxidase (GSH-Px), antioxidant enzymes, in erythrocyte, also C
      reactive protein (CRP) and erythrocyte sedimentation rate (ESR) were measured in
      22 patients in active stage of the disease and also in 30 healthy controls.
      Increased CRP, ESR, and MDA levels in plasma and erythrocyte and increased SOD
      but decreased GSH-Px activities in erythrocytes were observed in the patients,
      when compared to the controls. In addition, significantly positive correlations
      between plasma and erythrocyte MDA levels, and erythrocyte MDA-CRP, MDA-ESR, MDA
      SOD, SOD-ESR and SOD-CRP levels, but negative correlation between plasma MDA and
      erythrocyte GSH-Px, were found in BD patients. It may be suggested that increased
      production of ROS in BD, as reflected by higher plasma and erythrocyte MDA
      levels, may impair erythrocyte membrane integrity and also may lead to the
      alterations in the erythrocyte antioxidant defense system, as reflected by higher
      SOD and lower GSH-Px activities in erythrocytes.

PMID- 12180796
TI  - Immunohistochemical study on inducible type of nitric oxide (iNOS), basic
      fibroblast growth factor (bFGF) and tumor growth factor-beta1 (TGF-beta1) in
      arteritis induced in rats by fenoldopam and theophylline, vasodilators.
AB  - Arteritis induced in rats by vasodilators, fenoldopam and theophylline, was
      examined immunohistochemically for expressions of inducible type of nitric oxide
      synthase (iNOS), basic fibroblast growth factor (bFGF) and tumor growth factor
      beta1 (TGF-beta1). Rats were administered fenoldopam for 24 hours by intravenous
      infusion with or without following repeated daily oral administrations of
      theophylline. Irrespective of theophylline administration, iNOS antigens were
      remarkably abundant in ED-1-positive cells on day 5 and 8 post-fenoldopam
      infusion (DPI); bFGF antigens were remarkably abundant in ED-1-positive cells on
      1 and 3 DPI; TGF-beta1 antigens were observed in ED-1-positive cells on and after
      5 DPI. These results suggest that the peak expression of iNOS antigen was
      followed by that of bFGF antigen, and bFGF may have a suppressive effect on iNOS
      expression in these rat arteritis models. On the other hand, TGF-beta1 was not
      considered to have a suppressive effect on iNOS expression in these models.

PMID- 12180797
TI  - Renal interstitial fibrosis (RIF): II. Ultrasound follow up study of single
      uranyl nitrate administration causing renal dysfunction in rats--comparison with
      histologic and functional renal parameters.
AB  - A single administration of uranyl nitrate (UN; 0.5 mg/100 g b. wt. i.p.) to adult
      female Wistar rats reliably induces renal interstitial fibrosis (RIF) providing
      an experimental model to investigate therapeutic strategies. It was the aim of
      this study to further characterise a rat model of UN induced RIF which we have
      studied previously (Appenroth et al. 2001) by the comparison of functional
      parameters with ultrasonographic examination over a period of 30 weeks after
      injury. In the acute phase after UN administration (between days 2 and 17) signs
      of inflammation (increase in renal blood flow, swelling of renal cortex,
      enlargement of renal pelvis) could be detected by ultrasound. After four weeks UN
      led to functional changes (decreased creatinine clearance, increased urinary
      protein excretion and increased OH-proline concentration in renal tissue). In
      vitro, the accumulation of p-aminohippurate and the gluconeogenesis were reduced.
      In accordance with the functional changes, distinct ultrasonographic
      abnormalities could be seen between weeks 10 and 30 after UN with regard to
      changes in kidney size and shape, reduced renal perfusion and enlargement of
      renal pelvis. The sensitivity of ultrasonography in small laboratory animals is
      limited and most useful for follow-up studies of acute renal changes after
      administration of nephrotoxins. Ultrasonography can not be recommended for non
      invasive screening of the progression of chronic renal failure.

PMID- 12180799
TI  - Astrocytic response in the rodent model of global cerebral ischemia and during
      reperfusion.
AB  - The present study investigated alterations in astrocytic cells after global
      cerebral ischemia resulting from cardiac arrest immediately and at several
      intervals after reperfusion when excessive formation of highly cytotoxic free
      radicals is known to occur. The cellular fraction of astrocytic origin (glial
      plasmalemmal vesicles - GPV) was examined by biochemical and immunochemical
      procedures. A tendency towards an elevation in immunocontent of glial fibrillary
      acidic protein (GFAP) was noticed after 24 hours whereas a significant increase
      was observed 7 days post ischemic event. The features of astrocytic stimulation
      were also observed in electron microscopy studies. An enhanced amount of
      gliofilaments was noticed in brain sections obtained from rats after 7 days of
      recovery. Simultaneously, a gradual decrease of total glutathione level,
      depending on the duration of reperfusion, was observed in brain homogenates and
      in fractions of astroglial origin. The most considerable reduction was observed
      on day 1 (52%) and day 7 (65%) after reperfusion in brain homogenates and on day
      7 (47%) in GPV fraction. The results indicate an enhanced reactivity of
      astrocytic cells in ischemic conditions concomitantly with a long lasting
      decrease of total glutathione. Obviously, the inability of astrocytic glutathione
      system to detoxify free radicals formed during ischemic/reoxidation conditions
      may lead to damage to cerebral neurons by oxidative stress.

PMID- 12180798
TI  - A modified method to culture human osteoblasts from bone tissue specimens using
      fibrin glue.
AB  - INTRODUCTION: To establish primary osteoblast cultures is a challenge. The
      methods for isolation mostly comprise digestion with extracellular matrix
      degrading enzymes after mincing the bone samples. These methods are labour
      intensive and lead to an inefficient recovery of cells. Therefore, the aim of
      this study was to develop a more reliable method for culturing human osteoblasts.
      MATERIALS AND METHODS: Bone tissue specimens were obtained from 20 patients
      undergoing reconstructive operations. Bone specimens were dissected and put into
      petri dishes with the bottom covered with fibrin glue. To identify the nature of
      the outgrowing cells, cytological staining was performed, i.e. Von Kossa, Azan,
      Dahl's, alkaline phosphatase, and collagen type I. RESULTS: Mean time interval of
      cellular outgrowth was 12 days after preparing the bone tissue specimens.
      Confluence of the cell cultures was reached after four to five weeks on average.
      All cells were positively stained using Von Kossa, alkaline Phosphatase and
      collagen type I. The matrix consisted of lime, calcium and collagens. CONCLUSION:
      A simplified method to culture osteoblasts from all kinds of bone tissue
      specimens is presented. The fibrin glue allows firm adhesion of the specimens to
      the petri dish. This allows the cells to grow out without disturbance. Normally,
      due to movements during medium exchange the adhesive bonds are disrupted. The
      fibrin glue retains the adhesive bonds. This method allows studying human
      osteoblasts in different clinical settings.

PMID- 12180800
TI  - On a possible interrelationship among smoking, gastric ulceration and endogenous
      prostacyclin.
AB  - Investigating either in animals or in humans it seems that smoking exerts an
      unfavourable effect on the gastric mucosa. The target of this action (among
      others) is the endogenous prostacyclin content. In gastric ulceration there is a
      tendency toward decreased endogenous prostacyclin activity even in non-smoker
      patients, the decrease of which is more pronounced in smokers. The results of
      animal and human investigations draw attention once again to a possible role of
      smoking in the development and healing of peptic ulcer disease. Therefore it is
      always useful for sufferers to give up smoking.

PMID- 12180801
TI  - Dolichol content in isolated sinusoidal liver cells after in vivo chronic
      treatment with thioacetamide.
AB  - The content of dolichol, an isoprenoid present in all biological membranes, was
      determined in isolated sinusoidal liver cells after treatment of rats for 2 and 4
      months with a low dosage of the hepatotoxin thioacetamide. The significant
      decrease in dolichol observed in hepatocytes after 2 months might be explained by
      peroxidation of the isoprenoid. At the same time point, retinol was retained, and
      decreased only after 4 months of treatment. After 4 months of treatment therefore
      both lipids decreased. In a subfraction of hepatic stellate cells, Ito-1 cells,
      the main storage site of vitamin A, dolichol decreased significantly only after 4
      months. A remarkable difference from hepatocytes is that in Ito-1 cells retinol
      content significantly decreased after 2 months of treatment. In another
      subfraction, Ito-2 cells, the content of the two isoprenoids decreased in
      parallel. This heterogeneous subfraction might represent those transitional
      hepatic stellate cells that, while losing retinol, are in the process of
      differentiating into myofibroblasts secreting extracellular matrix components. In
      Kupffer cells and sinusoidal endothelial cells, impairment of dolichol might be
      observed later, only after 4 months of treatment, while retinol decreases
      uniformly over time. Starting after two months of treatment, the decrease of
      dolichol and the increase of retinol in hepatocytes, at the same time as retinol
      decreases in hepatic stellate cells, might be taken as an early index of
      incipient liver injury due to thioacetamide. This hypothesis is discussed with
      regard to a role of dolichol in the modulation of membrane fluidity for
      intracellular and intercellular retinol transport.

PMID- 12180802
TI  - Distinguishing between adverse and non-adverse effects. Session summary.

PMID- 12180803
TI  - Genetically modified foods: hazard identification and risk assessment. Session
      summary.
AB  - During a Joint Society of Toxicologic Pathology (STP)/International Federation of
      Societies of Toxicologic Pathologists (IFSTP) International Symposium, held
      between June 24 and 28, 2001, in Orlando, FL, USA, there was a session entitled
      as "Genetically Modified Foods: Hazard Identification and Risk Assessment". The
      purpose of this session was to present and discuss the current situations in the
      US, European Union and Japan for the public concerns, safety assessments and
      regulations on genetically modified (GM) products used as foods or food
      ingredients. Assuming the wide and fast growing of the usage of GM products, it
      is the duty for us as toxicologic pathologists, to supply reliable data on their
      safety and possible risks or hazards as a world-wide basis to not only
      governments or regulatory agencies but also general public of our countries.

PMID- 12180804
TI  - Acute myotoxic and nephrotoxic effects of Aipysurus laevis venom following
      intramuscular injection in mice.
AB  - We studied the local toxic effects on muscle and kidney following injections of
      incremental doses of crude Aipysurus laevis venom in mice. Mice were sacrificed
      at 24 hours after intramuscular injection. The soleus muscle and kidneys were
      examined by light microscopy. Injected muscle showed coagulative necrosis and
      inflammation, the severity of the damage increased with increasing dose of toxin
      injected, reaching a peak at a dose of 0.2 mg/kg body weight. Our findings
      suggest that the venom is directly myotoxic, mainly affecting mitochondrial rich
      fibres. The associated inflammatory response is probably secondary to muscle
      damage rather than a direct toxic effect of the venom. There is also renal damage
      which is more severe than that seen following subcutaneous venom injection in our
      previous studies. This can be explained by a more rapid absorption of injected
      venom.

PMID- 12180805
TI  - Cytophotometrical and immunohistochemical analysis of soft palate muscles of
      children with isolated cleft palate and combined cleft lip and palate.
AB  - Palatal muscle biopsies from the cleft margin of children were subjected to
      cytophotometrical and immunohistochemical analysis. Muscle fiber types were
      classified according to the enzyme activity of myofibrillic adenosine
      triphosphatase, glycerol-3-phosphate-dehydrogenase and succinate dehydrogenase
      assessed cytophotometrically. Fiber type-related immunoreactivity of nitric oxide
      synthase (NOS) isoforms I, II, III, as a physiological modulator of skeletal
      muscle function, was related to the oxidative and glycolytic activity of the
      muscle fibers. Fast oxidative glycolytic fibers with high oxidative activity
      showed strong NOS I immunoreactivity, whereas fast glycolytic fibers with high
      glycolytic activity were stronger immunolabelled for NOS III. NOS II expression
      was similar in all fiber types. No differences in NOS immunoreactivity were found
      between the two investigated forms of deformity. Additionally to the usual
      skeletal muscle fiber types, a slow tonic fiber type was for the first time
      identified in cleft palate muscles. Comparison of two forms of cleft palate,
      isolated cleft palate and combined cleft lip and palate has shown decreased
      enzyme activities in muscle fibers of palatal muscles from combined cleft lip and
      palate. Fast oxidative glycolytic fibers were mainly effected. Cytophotometrical
      and immunohistochemical analysis indicated a depressed performance of the cleft
      palatal muscles from combined cleft lip and palate as a stronger deformity
      compared with isolated cleft palate.

PMID- 12180806
TI  - Entacapone does not induce conformational changes in liver mitochondria or
      skeletal muscle in vivo.
AB  - Entacapone and tolcapone, novel catechol-O-methyl-transferase (COMT) inhibitors,
      have been developed for the treatment of Parkinson's disease in combination with
      levodopa. Three fatal cases of drug-induced hepatitis, one with hepatic necrosis
      and mitochondrial changes have been reported in clinical use of tolcapone. In
      vitro tolcapone has been shown to induce uncoupling of oxidative phosphorylation.
      Liver and skeletal muscle tissues from an oral rat toxicity study were used to
      investigate the influence of entacapone, tolcapone (300 and 500 mg/kg/day) or a
      known uncoupling agent, 2,4-dinitrophenol (DNP), (20 mg/kg/ day) on the cell
      morphology. Centrolobular hypertrophy was revealed in the histopathology of the
      liver in tolcapone-treated rats. Transmission electron microscopy (TEM) of the
      liver and skeletal muscle tissue, revealed mitochondrial swelling and reduced
      matrix density with deformation of cristae in the tolcapone and DNP groups.
      Intermyofibrillar edema was characteristic of the skeletal muscle tissue of DNP-
      and tolcapone-exposed animals. In the tolcapone group, also the sarcomeres were
      prominent. Treatment-related light microscopic or TEM findings were not observed
      either in entacapone-treated or control animals. The similarity of structural
      damages induced by both tolcapone- and DNP suggests that uncoupling of oxidative
      phosphorylation may contribute to the toxicity of tolcapone in the rat.

PMID- 12180807
TI  - Sequential anaerobic-aerobic treatment of an aquifer contaminated by halogenated
      organics: field results.
AB  - In situ, sequential, anaerobic to aerobic treatment of groundwater removed
      perchloroethene (PCE, 1.1 microM) and benzene (0.8 microM) from a contaminated
      aquifer. Neither aerobic nor anaerobic treatment alone successfully degraded both
      the chlorinated and non-chlorinated organic contaminants in the aquifer. After
      the sequential treatment, PCE, trichloroethene (TCE), vinyl chloride (VC),
      chloroethane (CA), and benzene were not detectable in groundwater. Desorption of
      residual aquifer contaminants was tested by halting the groundwater recirculation
      and analyzing the groundwater after 3 and 7 weeks. No desorption of the
      chlorinated contaminants or daughter products was observed in the treated portion
      of the aquifer. Sequential anaerobic to aerobic treatment was successful in
      remediating the groundwater at this test site and may have broad applications at
      other contaminated sites. Over the 4-year course of the project, the predominant
      microbial environment of the test site varied from aerobic to sulfate-reducing,
      to methanogenic, and back to aerobic conditions. Metabolically active microbial
      populations developed under all conditions, demonstrating the diversity and
      robustness of natural microbial flora in the aquifer.

PMID- 12180808
TI  - Virus transport in physically and geochemically heterogeneous subsurface porous
      media.
AB  - A two-dimensional model for virus transport in physically and geochemically
      heterogeneous subsurface porous media is presented. The model involves solution
      of the advection-dispersion equation, which additionally considers virus
      inactivation in the solution, as well as virus removal at the solid matrix
      surface due to attachment (deposition), release, and inactivation. Two surface
      inactivation models for the fate of attached inactive viruses and their
      subsequent role on virus attachment and release were considered. Geochemical
      heterogeneity, portrayed as patches of positively charged metal oxyhydroxide
      coatings on collector grain surfaces, and physical heterogeneity, portrayed as
      spatial variability of hydraulic conductivity, were incorporated in the model.
      Both layered and randomly (log-normally) distributed physical and geochemical
      heterogeneities were considered. The upstream weighted multiple cell balance
      method was employed to numerically solve the governing equations of groundwater
      flow and virus transport. Model predictions show that the presence of subsurface
      layered geochemical and physical heterogeneity results in preferential flow paths
      and thus significantly affect virus mobility. Random distributions of physical
      and geochemical heterogeneity have also notable influence on the virus transport
      behavior. While the solution inactivation rate was found to significantly
      influence the virus transport behavior, surface inactivation under realistic
      field conditions has probably a negligible influence on the overall virus
      transport. It was further demonstrated that large virus release rates result in
      extended periods of virus breakthrough over significant distances downstream from
      the injection sites. This behavior suggests that simpler models that account for
      virus adsorption through a retardation factor may yield a misleading assessment
      of virus transport in "hydrogeologically sensitive" subsurface environments.

PMID- 12180809
TI  - Axi-symmetric simulation of soil vapor extraction influenced by soil fracturing.
AB  - Fracturing, either pneumatic or hydraulic, is a method to improve the performance
      of soil vapor extraction (SVE) in relatively low permeability soils (< 10(-5)
      cm/s). A two-dimensional model is presented to simulate trichloroethylene (TCE)
      soil vapor extraction modified by fracturing. Flow and transport is modeled using
      mobile macropore and micropore networks, which also have been identified in the
      literature as dual porosity, dual permeability, or heterogeneous flow models. In
      this model, fluids can flow in both the macropore and micropore networks. This
      represents a more general model compared to immobile micropore, mobile macropore
      models presented thus far in the literature for vapor flow and transport in two
      dimensions. The model considers pressure- and concentration-driven exchange
      between the macropore and micropore networks, concentration-driven exchange
      between the gas and sorbed phases within each network, and equilibrium exchange
      between the gas and water and a sorbed phase within each network. The parameters
      employed in an example simulation are based on field measurements made at a
      fractured site. Considered in the simulations were the influence of the volume
      percentage of fractures, the length of fractures, the relative location of the
      water table, and the influence of pulsed pumping. For these simulations,
      internetwork concentration-driven exchange most significantly affected mass
      removal. The volume percentage of fractures more significantly influence flow and
      mass removal than the length of fractures. The depth of the water table below the
      contamination plume only significantly influenced flow and mass removal when the
      water table was within 60 cm of the bottom of the contaminated soil in the vadose
      zone for the parameters considered in this study. Pulsed pumping was not found to
      increase the amount of mass removed in this study.

PMID- 12180810
TI  - A laboratory technique for investigation of diffusion and transformation of
      volatile organic compounds in low permeability media.
AB  - A laboratory diffusion cell technique that permits spatial and temporal estimates
      of porewater concentrations over short intervals suitable for estimation of
      effective diffusion coefficients (De) and degradation rate constants (k) of
      volatile organic compounds (VOCs) in saturated low permeability media is
      presented. The diffusion cell is a sealed cylinder containing vapour reservoirs
      for sampling, including a vapour reservoir source and an array of vapour-filled
      "mini-boreholes", which are maintained water- and sediment-free by slightly
      negative porewater pressures. The vapour reservoirs were sampled by Solid Phase
      Micro-Extraction (SPME), resulting in minimal disturbance to the experimental
      system. Porewater concentrations are estimated from the measured vapour
      concentrations. Experiments were conducted using a non-reactive medium and five
      VOCs with a range in partitioning properties. Calibration experiments showed that
      equilibrium partition coefficients could be used for calculating concentrations
      in the vapour reservoir source from concentrations in the SPME coating after a 1
      min microextraction and that the reservoir concentration was insignificantly
      affected by sampling. However, equilibrium was not reached during the one-min
      extraction of the boreholes; the microextraction reduced the borehole vapour
      concentrations, leading to diffusion of VOCs from porewater into the vapour
      filled borehole. Thus, empirical partitioning coefficients were required for the
      determination of porewater VOC concentrations. The experimental data and
      numerical modelling indicate masses extracted by SPME extraction are relatively
      small, with minimal perturbation on processes studied in diffusion experiments.
      This technique shows promise for laboratory investigation of diffusion and
      transformation processes in low permeability media.

PMID- 12180811
TI  - Effect of pore-water velocity on chemical nonequilibrium transport of Cd, Zn, and
      Pb in alluvial gravel columns.
AB  - This paper investigates the effects of pore-water velocity on chemical
      nonequilibrium during transport of Cd, Zn, and Pb through alluvial gravel
      columns. Three pore-water velocities ranging from 3 to 60 m/day were applied to
      triplicate columns for each metal. Model results for the symmetric breakthrough
      curves (BTCs) of tritium (3H2O) data suggest that physical nonequilibrium
      components were absent in the uniformly packed columns used in these studies. As
      a result, values of pore-water velocity and dispersion coefficient were estimated
      from fitting 3H2O BTCs to an equilibrium model. The BTCs of metals display long
      tailing, indicating presence of chemical nonequilibrium in the system, which was
      further supported by the decreased metal concentrations during flow interruption.
      The BTCs of the metals were analysed using a two-site model, and transport
      parameters were derived using the CXTFIT curve-fitting program. The model results
      indicate that the partitioning coefficient (beta), forward rate (k1), and
      backward rate (k2) are positively correlated with pore-water velocity (V); while
      the retardation factor (R), mass transfer coefficient ((omega), and ratio of
      k1/k2 are inversely correlated with V. There is no apparent relationship between
      the fraction of exchange sites at equilibrium (f) and V. The influence of Von k2
      is much greater than on R, beta, omega, and k1. A one-order-of-magnitude change
      in V would cause a two-order-of-magnitude change in k2 while resulting in only a
      one order-of-magnitude change in R, beta, omega, and k1. The forward rates for
      the metals are found to be two to three orders-of-magnitude greater than the
      corresponding backward rate. However, the difference between the two rates
      reduces with increasing pore-water velocity. Model results also suggest that Cd
      and Zn behave similarly, while Pb is much more strongly sorbed. At input
      concentrations of about 4 mg/l and pore-water velocities of 3-60 m/day in the
      groundwater within alluvial gravel, this study suggests retardation factors of 26
      289 for Cd, 24-255 for Zn, and 322-6377 for Pb.

PMID- 12180812
TI  - Two-site kinetic modeling of bacteriophages transport through columns of
      saturated dune sand.
AB  - Breakthrough curves, on a semi-log scale, from tests in porous media with block
      input of viruses, bacteria, protozoa and colloidal particles often exhibit a
      typical skewness: a rather slowly rising limb and a smooth transition of a
      declining limb to a very long tail. One-site kinetic models fail to fit the
      rising and declining limbs together with the tail satisfactorily. Inclusion of an
      equilibrium adsorption site does not seem to improve simulation results. This was
      encountered in the simulation of breakthrough curves from a recent field study on
      the removal of bacteriophages MS2 and PRD1 by passage through dune sand. In the
      present study, results of laboratory experiments for the study of this issue are
      presented. Breakthrough curves of salt and bacteriophages MS2, PRDI, and phiX174
      in 1 D column experiments have been measured. One- and two-site kinetic models
      have been applied to fit and predict breakthrough curves from column experiments.
      The two-site model fitted all breakthrough curves very satisfactorily, accounting
      for the skewness of the rising limb as well as for the smooth transition of the
      declining limb to the tail of the breakthrough curve. The one-site model does not
      follow the curvature of the breakthrough tail, leading to an overestimation of
      the inactivation rate coefficient for attached viruses. Interaction with kinetic
      site 1 is characterized by relatively fast attachment and slow detachment,
      whereas attachment to and detachment from kinetic site 2 is fast. Inactivation of
      viruses and interaction with kinetic site 2 provide only a minor contribution to
      removal. Virus removal is mainly determined by the attachment to site 1.
      Bacteriophage phiX174 attached more than MS2 and PRD1, which can be explained by
      the greater electrostatic repulsion that MS2 and PRD1 experience compared to the
      less negatively charged phiX174.

PMID- 12180813
TI  - Development and verification of a screening model for surface spreading of
      petroleum.
AB  - Overflows and leakage from aboveground storage tanks and pipelines carrying crude
      oil and petroleum products occur frequently. The spilled hydrocarbons pose
      environmental threats by contaminating the surrounding soil and the underlying
      ground water. Predicting the fate and transport of these chemicals is required
      for environmental risk assessment and for remedial measure design. The present
      paper discusses the formulation and application of the Oil Surface Flow Screening
      Model (OILSFSM) for predicting the surface flow of oil by taking into account
      infiltration and evaporation. Surface flow is simulated using a semi-analytical
      model based on the lubrication theory approximation of viscous flow. Infiltration
      is simulated using a version of the Green and Ampt infiltration model, which is
      modified to account for oil properties. Evaporation of volatile compounds is
      simulated using a compositional model that accounts for the changes in the
      fraction of each compound in the spilled oil. The coupling between surface flow,
      infiltration and evaporation is achieved by incorporating the infiltration and
      evaporation fluxes into the global continuity equation of the spilled oil. The
      model was verified against numerical models for infiltration and analytical
      models for surface flow. The verification study demonstrates the applicability of
      the model.

PMID- 12180814
TI  - Comment on "Model coupling intra-particle diffusion/sorption, nonlinear sorption,
      and biodegradation process" by H.K. Karapanagioti, C.M. Gossard, K.A. Strevett,
      R.L. Kolar, and D.A. Sabatini.

PMID- 12180815
TI  - Rejection of grafts with no H-2 disparity in TAP1 mutant mice: CD4 T cells are
      important effector cells and self H-2b class I molecules are target.
AB  - Our previous results showed that TAP1 mutant mice rejected heart and skin grafts
      from donors with no H-2 disparity that express normal density of MHC class I
      molecules at the cell surface. During rejection, CD4 cells were predominant and
      essentially, no CD8 cells were found infiltrating the grafts. We hypothesized
      that TAP1 mutant mice, which developed and matured in an MHC class I-deficient
      environment, may have selected a repertoire of T cells with distinct reactivity
      to self class I molecules. The rejection of grafts with no H-2 disparity could be
      mediated by CD4+ T cells reactive to wild type H-2b class I molecules, or derived
      peptides, in the context of self-APC. Accordingly, we observed that transplanted
      TAP1 mutant mice presented a significant amplification of the proliferative T
      cell response to H-2Kb peptides, indicating that the stimulus with the graft was
      sufficient to induce peripheral expansion of these T cell repertoires. Therefore,
      the response to H-2Kb molecules could be a relevant pathway of activating T cells
      and triggering rejection of grafts expressing normal levels of these class I
      molecules. To test our hypothesis, we investigate the effect of pre
      transplantation H-2Kb peptide-immunization on TAP1 mutant, which were then
      transplanted with C57BL/6 skin grafts (H-2b). Mice were immunized with a pool of
      five peptides derived from the polymorphic region of Kb alpha chain, before tail
      skin grafting. To study the role of CD4+ T cells in the rejection of C57BL/6 skin
      grafts, mice were in vivo depleted with an anti-CD4 monoclonal antibody GK1.5,
      and transplant evolution was observed. Sensitization of TAP1 mutant mice with H
      2Kb peptides accelerated the rejection of skin grafts. Immunized mice rejected
      grafts with a MST of 13 days, compared to 16 days for the non-immunized mice
      (P=0.0089). The significant acceleration of graft rejection, induced by
      immunization with H-2Kb peptides, indicates that these peptides are capable of
      mobilizing effector T-cells that participate in rejection. These results support
      our hypothesis that class I molecules may be a target in the rejection of grafts
      with no MHC disparity. Depletion of CD4 T-cells resulted in a significant delay
      in rejection compared with the untreated control group. The MST of skin grafts in
      the controls was 16 days, whereas CD4-depleted recipients rejected skin grafts
      with a MST of 41 days (P=0.025). Moreover, some animals did not show macroscopic
      signs of rejection up to > 100 days posttransplantation. The contribution of CD4+
      T cells to skin graft rejection, in our model, may reflect the occurrence of the
      presentation of H-2b peptides during graft rejection, in the context of self-APC.
      In conclusion, our results demonstrate an important role for H-2b molecules and
      CD4 T cells in the rejection of C57BL/6 grafts by TAP1 mutant mice. The low
      expression of MHC-I molecules on TAP1-/- mice may be determinant in the selection
      of a T cell repertoire strongly reactive to self MHC class I molecules which
      probably escapes the control of peripheral regulatory mechanisms.

PMID- 12180816
TI  - NK cells and transplantation.
AB  - The requirement for cytotoxic T lymphocytes during allograft rejection is
      controversial. We have demonstrated that CD8+ T cells are not essential for
      allograft rejection or for the induction of apoptosis in two experimental models
      of transplantation. To determine candidate cells types which may play a role in
      the events leading to graft rejection, the cellular composition of rejecting
      allografts was determined. We demonstrate that substantial numbers of NK cells,
      of recipient origin, infiltrate allografts as early as 12 h after
      transplantation. These NK cells produce cytokines and express cytotoxic mediators
      such as granzyme B and FasL. It is unknown which NK cell receptors are expressed
      and activated during transplantation. NK cells express multiple cell surface
      receptors, including MHC class I binding inhibitory receptors, which deliver a
      negative signal, and activation receptors, which stimulate cytokine secretion and
      cytotoxicity of NK cells. To begin to understand NK cell activation in the
      context of transplantation, we have recently cloned a novel rat immunoglobulin
      like surface receptor from a rejecting liver allograft. Sequence analysis
      demonstrates that this putative activation receptor contains 71% identity to
      human NKp30 at the DNA level, suggesting that it is the rat homologue (rNKp30).
      Characterization of NK activation receptors may lead to better understanding of
      the interactions between the innate and adaptive immune responses in
      transplantation.

PMID- 12180817
TI  - The role of IL6 cytokines in acute cardiac allograft rejection.

PMID- 12180818
TI  - The role of interleukin-10 in lung transplantation.
AB  - Interleukin-10 (IL-10) is a pleiotropic cytokine and its main function is to
      limit and terminate inflammatory responses. Lung transplantation is a relatively
      young clinical field compared to the transplantation of other solid organs and
      long-term survival is still limited. Complications after lung transplantation
      include ischemia-reperfusion injury immediately after transplantation, acute
      rejection and infection within the first year after transplantation and chronic
      allograft dysfunction in form of bronchiolitis obliterans thereafter. In the
      setting of lung transplantation two key functions of IL-10 might be of interest:
      (1) the inhibition of inflammatory immune responses; and (2) the inhibition of T
      cell mediated immune responses. In animal models, it has been shown that
      exogenous IL-10 is able to prevent posttransplant ischemia-reperfusion injury as
      well as to decrease acute rejection. It was also effective in preventing airway
      obliteration in an animal model of posttransplant bronchiolitis obliterans.
      Beneficial effects of IL-10 may be found early and late after lung
      transplantation. Location of IL-10 expression as well as the timing of
      administration seems to be important for the desired effects.

PMID- 12180819
TI  - Tolerance through bone marrow transplantation with costimulation blockade.
AB  - The routine induction of tolerance in organ transplant recipients remains an
      unattained goal. The creation of a state of mixed chimerism through allogeneic
      bone marrow transplantation leads to robust donor-specific tolerance in several
      experimental models and this approach has several features making it attractive
      for clinical development. One of its major drawbacks, however, has been the
      toxicity of the required host conditioning. The use of costimulation blocking
      reagents (anti-CD 154 monoclonal antibodies and the fusion protein CTLA4Ig) has
      led to much less toxic models of mixed chimerism in which global T cell depletion
      of the host is no longer necessary and which has even allowed the elimination of
      all cytoreductive treatment when combined with the injection of very high doses
      of bone marrow cells. In this overview we will briefly discuss general features
      of tolerance induction through bone marrow transplantation, will then describe
      recent models using costimulation blockade to induce mixed chimerism and will
      review the mechanisms of tolerance found with these regimens. Finally we will
      attempt to identify issues related to the clinical introduction of bone marrow
      transplantation with costimulation blockade which remain unresolved.

PMID- 12180820
TI  - The graft unveils its secrets: provocative therapeutic leads to protected
      vascularized allografts.

PMID- 12180821
TI  - The graft helps to define the character of the alloimmune response.
AB  - INTRODUCTION: In mice, kidney and liver allografts may be spontaneously accepted,
      whereas cardiac and skin allografts in the same strain combinations are rapidly
      rejected. The reasons for this dichotomy in murine response outcomes remains to
      be determined. METHODS AND RESULTS: When DBA/2 (H-2d) cardiac allografts were
      placed in C57BL/6 (H-2b) recipients, they were rejected within 10 days, unless
      the allograft recipients were transiently treated with gallium nitrate (GN), at
      which time the allografts were accepted for > 150 days. The cardiac allograft
      rejector mice displayed DBA/2-reactive DTH responses, whereas the cardiac
      allograft acceptor mice displayed both TGFbeta- and IL10-mediated inhibition of
      DTH responses. In contrast, DBA/2 kidney allografts placed at the same location
      in C57BL/6 mice were spontaneously accepted without immunosuppression. These
      kidney allograft acceptor mice displayed TGFbeta-mediated, but not IL10-mediated
      inhibition of donor-reactive DTH responses. CONCLUSIONS: In the DBA/2-> C57B1/6
      strain combination, cardiac allografts induce pro-inflammatory immunity and
      allograft rejection, while kidney allografts induce anti-inflammatory immunity
      and allograft acceptance despite the fact that both organs display the same
      strong MHC disparities and are implanted at the same location. Anti-inflammatory
      immunity and allograft acceptance are displayed by cardiac allograft recipients
      when they are transiently treated with select immunosuppressants. Thus, multiple
      immune response options are available to the organ allograft recipient, and the
      choice is determined, to some degree, by the allograft, itself.

PMID- 12180822
TI  - Evidence that a similar range of alloimmune responses can develop in murine and
      human allograft recipients.
AB  - Based on discrepancies between various laboratory and clinical observations,
      skepticism has developed regarding the pre-clinical value of rodent immunologic
      studies. In this article, we review the progression of our murine and human
      studies over the last several years, which have demonstrated that humans and mice
      can make very similar types of immune responses in vivo to allografts. Early
      studies by ourselves and others, demonstrated that mice can make either pro
      inflammatory (rejection) or anti-inflammatory (acceptance) immune responses to
      graft alloantigens. We demonstrated that donor-reactive DTH assays could be used
      to monitor which type of alloimmune response had been selected by the allograft
      recipient. To help determine if similar immune response options are available to
      humans and detectable by DTH assays, we first developed the transvivo DTH assay.
      In this system, mice are used as a receptacle in which DTH responses made by
      human PBMC can be induced and measured. These transvivo DTH studies revealed that
      human allograft recipients, like mice, commonly make either pro-inflammatory or
      anti-inflammatory immune responses to graft alloantigens. In transplant patients,
      this rarely correlates with the development of donor-reactive alloantibodies
      during the post-transplant period.

PMID- 12180823
TI  - Developmental aspects of immunomodulation: exploiting the immature immune system
      for organ transplantation.

PMID- 12180824
TI  - Immunology of pregnancy-pregnancy as a remission inducing agent in rheumatoid
      arthritis.
AB  - A variety of hormonal and immunological alterations are induced by pregnancy in
      order to protect the semi-allogeneic fetus from rejection. Systemic effects of
      altered immunoregulation induced by pregnancy influence the activity of
      rheumatoid arthritis (RA) and other autoimmune diseases. Pregnancy induces
      improvement or even remission of disease activity in 75% of RA patients. This
      phenomenon has still not been explained, however, several attractive hypotheses
      related to the immunology of pregnancy emerge. Pregnancy polarizes the immune
      response towards a TH2 response, which may counterbalance the augmented TH1
      response observed in RA. The increase of circulating inhibitors of
      proinflammatory cytokines occurring in pregnancy could act as a potent anti
      inflammatory agent in joint inflammation. In what way the induction of T cell
      tolerance to fetal antigens or maternal-fetal HLA disparity modulates disease
      activity of RA has not been studied. The concept of regulatory T cells has been
      discussed in the context of pregnancy, but until now has not been substantiated
      by experimental data. In conclusion, pregnancy influences the signs and symptoms
      of RA, but not the underlying autoimmune process. It remains to be investigated
      if a single event like neutralisation of proinflammatory cytokines or an
      interplay between circulating and cellular mechanisms is the key to remission.

PMID- 12180825
TI  - Pregnancy in renal transplantation: immunologic evaluation of neonates from
      mothers with transplanted kidney.
AB  - The occurrence of pregnancy in young female organ transplant recipients may
      sustain a high risk for prematurity and low rate of malformations in neonates.
      Therefore, it is necessary to counsel couples who want a child. In case of
      pregnancy, strict guidelines must be observed. Continuous exposure to CsA in
      utero seems to impair T-, B- and NK-cell development and function in neonates.
      This effect is prolonged throughout the first year of life. In addition, low
      levels of serum immunoglobulins occur at the same time. This leads to suggest a
      delayed administration of classical vaccinations (after the first 6 months of
      life) in view of the potential risks of both sub-optimal immunologic responses,
      and adverse events after the administration of live, attenuated vaccines in
      infants born from young female organ transplant recipients.

PMID- 12180826
TI  - Replicative senescence in organ transplantation-mechanisms and significance.
AB  - In the past two decades, transplantation has become a preferred modality of
      treatment of end-stage failure of vital organs. Currently, with the significant
      improvement in short-term graft survival rates, the main effort is concentrated
      on prolonging the functional life span of transplanted organs. One of the
      theories which were put forward to explain the progressive deterioration of
      transplant function was that of replicative senescence. Senescence of an organ or
      tissue results from age and/or environmental stress-dependant modification of
      cellular function. With time, the accumulation of cellular alterations may lead
      to deleterious effects in various organs and tissues and adversely affect
      transplants. In this article we are reviewing the candidate mechanisms of
      senescence such as telomere shortening, genetic regulation and environmental
      'toxic' factors and are examining the implications of the theory of replicative
      senescence for organ allograft. We are also presenting our experiments with renal
      ischemia/reperfusion in rat serving as a model of kidney transplantation, where
      baseline kidney telomere length and novel marker of cellular senescence-
      senescence associated beta-Galactosidase (SA-Gal) expression in tissue served as
      markers. For the first time in vivo, we were able to show that with aging of the
      animals the amount of senescent cells in kidney tissue was increasing, while the
      average renal tissue telomere length was decreasing. The degree of tissue
      senescence, as determined by amount of SA-Gal positively stained cells, was
      inversely correlated with the recovery of the kidney function after
      ischemia/reperfusion injury. These results confirm the theory of replicative
      senescence in organ ischemia for the first time in vivo, and quantitatively
      validate the direct correlation between the amount of senescent cells in the
      organ and its susceptibility to ischemic injury. We conclude that recent advances
      in study of the cellular basis of senescence, in vitro and especially in vivo,
      may hold clues to the understanding of events which could be implicated in the
      damage or protection of organ allografts.

PMID- 12180827
TI  - Molecular basis of HLA polymorphism: implications in clinical transplantation.
AB  - Polymorphism of the human leukocyte antigens (HLA) represents a major barrier to
      organ and hematopoietic stem cell (HSC) transplantation. The cloning and
      sequencing of HLA class I and II genes has not only provided a clear picture of
      the molecular basis of allelic polymorphism, but also allowed the development of
      a variety of PCR-based DNA typing techniques. Such methods are now progressively
      replacing serological typing for assessing donor/recipient HLA compatibility in
      clinical transplantation. The 100 serological HLA-A,B,Cw,DR,DQ,DP specificities
      now comprise more than 1300 alleles defined at the DNA sequence level. Most of
      the serotypes are subdivided into numerous allelic subtypes in worldwide
      populations (up to 50 alleles in some cases), although a limited number of
      alleles are detected in a given population group. In organ transplantation
      application of HLA molecular typing allowed to improve typing quality, leading to
      a more precise matching assessment with better clinical results. Knowledge of the
      molecular basis of class I gene polymorphisms also led to the development of new
      matching algorithms such as HLA-Matchmaker, based on immunogenic amino acid
      triplets localized on antibody-accessible external domains of class I antigens.
      The most impressive impact of novel DNA typing methods concerns matching for
      allogeneic HSC transplantation because subtle serologically silent sequence
      differences between allelic subtypes are efficiently recognized by alloreactive T
      cells with potentially serious consequences for graft outcome. High resolution
      HLA class I and II matching has contributed to improve patients survival after
      unrelated HSC transplantation, although the relative importance of individual
      loci remains to be elucidated. Donor matching criteria should take into account
      parameters such as the time frame allowed by the patient's disease and the
      probability to identify a well matched donor based on the patient's HLA
      phenotype.

PMID- 12180828
TI  - Anti-adhesion antibodies efalizumab, a humanized anti-CD11a monoclonal antibody.
AB  - The acquired immune response that leads to graft rejection depends on regulated
      adhesive interactions between T lymphocytes, endothelial cells, dendritic cells,
      graft tissue and the extracellular matrix to coordinate cellular trafficking and
      activation of antigen-reactive T lymphocytes. Inhibiting the function of
      molecules involved in the adhesion processes offers the potential for interfering
      with the allograft response. The leukocyte function associated antigen-1 molecule
      (LFA-1), a heterodimer of CD11a (alphaL) and CD18 (beta2) integrin subunits, is
      an attractive therapeutic target because it plays an important role in key steps
      of inflammation and tissue rejection. These include: (1) binding of leukocytes to
      endothelium; (2) trafficking through activated endothelium; and (3) costimulatory
      interactions between T lymphocytes and antigen presenting cells. Clinical
      experience with efalizumab, a humanized anti-CD11a monoclonal antibody (mAb), in
      patients with chronic plaque psoriasis has shown that anti-CD11a therapy is well
      tolerated and effective at reducing the severity of the disease without depleting
      lymphocytes. Initial results in renal transplant patients are also promising.

PMID- 12180829
TI  - Mycophenolate sodium: tolerability and efficacy in transplantation in the rat.
AB  - Inhibition of inosine monophosphate dehydrogenase by mycophenolate compounds
      results in potent immunosuppression, as demonstrated by the efficacy of the
      marketed prodrug mycophenolate mofetil (MMF) in clinical allotransplantation.
      Side effects are well-known and include bone marrow depression and
      gastrointestinal intolerability. Mycophenolate sodium (MPS) is in clinical
      development as an enteric-coated formulation to alleviate this gastrointestinal
      adverse effect. Accompanying this development, MPS and MMF were evaluated in a
      tolerability study in rats and in efficacy studies in rat allo- and
      xenotransplantation models. The compounds were given either singly or in
      combination with cyclosporine A and were efficacious in the prevention of allo-
      or xeno-graft rejection, but with a rather narrow window between optimal
      immunosuppression and adverse side effects. For instance, the minimal effective
      dose to prevent rejection of a kidney or heart allograft or a hamster heart
      xenograft is a daily dose of 10-20 mg/kg MPS, at which dose the first adverse
      side effects can be observed: the compound at 40 mg/kg is not tolerated. This
      window is even narrower for MMF than for MPS, and in most models, a minimal
      effective MMF dose could not be established. The window between optimal
      immunosuppression and adverse side effects is larger when the compounds are given
      in combination with cyclosporine A: in all models investigated combinations were
      established yielding long-term survival without histologic signs of rejection and
      without signs of side effects. Thus, the combination of an IMPDH inhibitor (MPS,
      MMF) and a calcineurin inhibitor (cyclosporine A) enables fine-tuning in
      achieving optimal immunosuppression avoiding drug side effects.

PMID- 12180831
TI  - Rational drug design.

PMID- 12180830
TI  - Statins as immunomodulators.
AB  - HMG-CoA reductase inhibitors, or statins, are effective lipid lowering agents,
      extensively used in medical practice. Statins have never been shown to be
      involved in the immune response, although few clinical reports have suggested a
      better outcome of cardiac transplantation in patients under pravastatin therapy.
      Major histocompatibility complex class II (MHC-II) molecules are directly
      involved in the activation of T lymphocytes and in the control of the immune
      response. Whereas only a limited number of specialized cell types express MHC-II
      constitutively, numerous other cells become MHC-II positive upon induction by
      interferon gamma (IFN-gamma). We and others recently demonstrated that statins
      act as direct inhibitors of induction of MHC-II expression by IFN-gamma and thus
      as repressors of MHC-II-mediated T cell activation. This effect was observed in
      several cell types, including primary human endothelial cells and macrophages.
      Interestingly, this inhibition is specific for inducible MHC-II expression and
      does not concern either constitutive expression of MHC-II or expression of MHC-I.
      In repressing induction of MHC-II, and subsequent T lymphocyte activation,
      statins therefore behave as a novel type of immunomodulator. This unexpected
      effect provides a scientific rationale for suggesting the use of statins as novel
      immunosuppressors, not only in organ transplantation but in numerous other
      pathologies as well.

PMID- 12180832
TI  - Insights into pharmacogenomics and its impact upon immunosuppressive therapy.
AB  - The advent of the genomic era has brought about several new fields of study, one
      of them being pharmacogenomics, which seeks to link drug treatment (pharmaco-)
      with the individual's genetic make-up (genomics). Pharmacogenomics holds many
      promises for improved treatment of a large variety of medical conditions,
      including immunosuppression for organ transplantation and autoimmune disease.
      Many of these promises have, however, not yet been fulfilled. In this brief
      overview of the subject, we attempt to provide insights into the evolving field
      of pharmacogenomics and discuss some of its potential benefits and promises,
      technological tools used by pharmacogenomics, the reasons for delays in
      breakthroughs in the field, and the relevance of pharmacogenornics to
      immunosuppression.

PMID- 12180833
TI  - How pharmacokinetic and pharmacodynamic drug monitoring can improve outcome in
      solid organ transplant recipients.
AB  - Within the field of solid organ transplantation there is an unprecedented
      interest in therapeutic drug monitoring of immunosuppressive drugs. Ideally
      therapeutic drug monitoring should cost-effectively lead to improved efficacy of
      the drug and to a reduction in side effects. Therapeutic drug monitoring will be
      most effective if there is a large interpatient variability and a small
      intrapatient variability. Therapeutic drug monitoring in transplantation is
      largely based on correlations between drug concentrations and toxicity or between
      drug concentrations and efficacy. Pharmacodynamic monitoring of immunosuppressive
      drugs has not reached the stage of widespread clinical application. In part this
      is caused by the fact that most of the pharmacodynamic assays are time-consuming,
      costly and in some cases only give a result after several days of incubation.
      Another reason for the limited interest in pharmacodynamic monitoring is the lack
      of data showing improved outcome if dose adjustment is based on pharmacodynamics
      rather than pharmacokinetics. On the other hand, such data are also lacking for
      pharmacokinetic monitoring. Prospective investigations on the contribution of
      therapeutic drug monitoring may result in further improvement of the safety and
      efficacy of our immunosuppressive regimens and more refined methods for
      therapeutic drug monitoring. There is no contest between pharmacokinetic and
      pharmacodynamic monitoring. Most likely the results of both ways of monitoring
      will be complementary.

PMID- 12180834
TI  - New concepts in organ preservation.
AB  - Organ preservation between donor and recipient is an important link in a chain
      that ultimately should lead to long term survival of the recipient thanks to a
      well-preserved, functionally intact organ. The period of organ ischaemia outside
      the body is subject to a number of biochemical stress factors which become known
      in more detail as knowledge on biochemical and immunological mechanisms improves.
      Efficacy of preservation fluids hence reduction of ischaemia injury may become
      enhanced by such additives as ion channel blockers, enzyme inhibitors, haeme
      oxygenase modulators, endothelin-l-inhibitors, quenchers of free radicals and
      anti-apoptotic agents. Many of these compounds, albeit of great theoretical
      interest, have not (yet?) made their way into clinical practice. This
      contribution is a survey of some promising agents, concentration and
      physicochemical interactions of which are analysed in some detail.

PMID- 12180835
TI  - A novel strategy against ischemia and reperfusion injury: cytoprotection with
      heme oxygenase system.
AB  - Much interest has recently been focused on the physiological/pathological role of
      the heme oxygenase (HO) system, the rate-limiting step in the conversion of heme,
      in inflammatory events. The HO system may be instrumental in mediating a number
      of cytoprotective effects, because of its end products, biliverdin, carbon
      monoxide (CO) and ferrous free iron (Fe2+). As each of the byproducts acts
      dependently and/or co-operatively with each other, their in vivo effects are
      complex. In general, the HO system is thought to exert three major functions in
      ischemia/reperfusion injury: (1) anti-oxidant effects; (2) maintenance of
      microcirculation; and (3) modulatory effects upon the cell cycle. The anti
      oxidant functions depend on heme degradation, oxygen consumption and the
      production of biliverdin/ferritin via iron accumulation. On the other hand, the
      production of CO, which has vasodilatory and anti-platelet aggregative
      properties, can maintain tissue microcirculation. Strikingly, CO may also be
      instrumental in anti-apoptotic and cell arrest mechanisms. The HO system prevents
      early injury in the re-perfused organ, and inhibits the function of immune
      reactive cells, such as neutrophils, macrophages and lymphocytes. The role of the
      HO system as a novel strategy to mitigate an antigen-independent
      ischemia/reperfusion injury has been documented in a number of transplantation
      models.

PMID- 12180836
TI  - Inhibition of graft arteriosclerosis development in rat aortas following heme
      oxygenase-1 gene transfer.
AB  - Heme oxygenase 1 (HO-1) is an enzyme which degrades heme into tree end products:
      biliverdin, free iron and carbon monoxide. This enzyme has recently been shown to
      have anti-inflammatory and tissue protective effects. HO-1 expression is involved
      in organ protection in pathological situations, and immunosuppressive treatments
      resulting in indefinite graft survival without chronic rejection have been
      associated with HO-1 expression by cells of the vessel wall. The aim of this
      study was to analyze the effect of specific HO-1 overexpression. We used a
      recombinant adenovirus coding for human HO-1 cDNA in a rat aorta chronic
      rejection model, 30 days after transplantation. Control groups included rats non
      treated or treated with a non-coding adenovirus Addl324. We first demonstrated
      that AdHO-1 was efficiently expressed in endothelial cells in vitro, and in rat
      aortas ex vivo after adenovirus gene transfer. We found that intimal thickening
      in AdHO-1 treated aortas (10.8 +/- 3.8%, n=5) was significantly decreased
      compared to untreated (21.2 +/- 5.6%, n = 5) or Addl324-treated (21.1 +/- 1.2%, n
      = 4) aortas. Immunohistology showed that treatment with AdHO-1 resulted in a
      significant reduction in leukocyte infiltration and a decreasing number of VSMC
      in the intima, compared to Addl324-treated aortas. However, this effect of HO-1
      on chronic rejection did not imply modifications on numbers of apoptotic cells in
      the graft or of alloantibody levels. We have demonstrated, for the first time,
      that specific HO-1 overexpression following gene transfer of HO-1 inhibited
      chronic rejection by reducing leukocyte and VSMC infiltration of the aorta
      intima.

PMID- 12180837
TI  - Survival pathways and preconditioning in liver transplantation.

PMID- 12180838
TI  - Microvascular prothrombogenicity and transplant coronary artery disease.
AB  - A major impediment for the long-term success of heart transplantation is the
      development of transplant coronary artery disease (CAD). Several risk factors for
      the development of transplant CAD are associated with the transformation of a
      normal thromboresistant microvasculature into a prothrombogenic microvasculature.
      Prothrombogenicity is characterized by loss of anticoagulation (i.e. loss of
      antithrombin), loss of fibrinolytic activity (i.e., loss of tissue plasminogen
      activator) and presence of endothelial activation (i.e. upregulation of
      endothelial intercellular adhesion molecule-1 and major histocompatibility class
      II antigen human leukocyte antigen-DR) in the arterial allograft
      microvasculature. Microvascular prothrombogenicity during the first trimester
      after transplantation is directly associated with subsequent development of
      transplant CAD. Although the mechanisms responsible for the loss of
      thromboresistant endothelium are unclear, the fact that changes in the
      anticoagulant, fibrinolytic, and activational status of endothelial cells may
      occur early after transplantation suggests a peritransplant phenomenon as an
      initiating event. Reducing prothrombogenicity of the cardiac microvasculature
      early after transplantation could slow the development of transplant CAD and
      significantly improve allograft survival.

PMID- 12180839
TI  - Xenotransplantation--how far have we come?
AB  - The immunologic barriers to xenotransplantation are summarized and approaches to
      overcome them briefly reviewed. Intensive investigation is being directed to the
      problem of acute humoral xenograft rejection, which is the major current barrier.
      Although the induced antibody response appears to be prevented by combination
      therapy with an anti-CD154 monoclonal antibody and mycophenolate mofetil,
      deposition of natural anti-Gal antibody on the graft endothelial cells appears to
      be sufficient to lead to rejection or a state of consumptive coagulopathy.
      Approaches towards the induction of tolerance are described. The potential
      microbiologic risks and physiologic incompatibilities of pig-to-human organ
      transplantation are also briefly discussed.

PMID- 12180840
TI  - Antibody-mediated activation of the classical complement pathway in xenograft
      rejection.
AB  - Transplant rejection is a multifactorial process involving complex interactions
      between components of the innate and the acquired immune system. In view of the
      shortage of donor organs available for transplantation, xenotransplantation of
      pig organs into man has been considered as a potential solution. However, in
      comparison to allografts, xenografts are subject to extremely potent rejection
      processes that are currently incompletely defined. Consequently, an appropriate
      and safe treatment protocol ensuring long-term graft survival is not yet
      available. The first barrier that has to be taken for a xenograft is hyperacute
      rejection, a rapid process induced by the binding of pre-formed antibodies from
      the host to the graft endothelium, followed by activation of the classical
      complement pathway. The present review concentrates on the role of antibodies and
      complement in xenograft rejection as well as on the approaches for treatment that
      target these components. The first part focuses on porcine xenoantigens that are
      recognized by human xenoreactive antibodies and the different treatment
      strategies that aim on interference in antibody binding. The second part of the
      review deals with complement activation by xenoreactive antibodies, and
      summarizes the role of complement in the induction of endothelial cell damage and
      cell activation. Finally, various options that are currently under development
      for complement inhibition are discussed, with special reference to the specific
      inhibition of the classical complement pathway by soluble complement inhibitors.

PMID- 12180841
TI  - Activation of complement pathways in xenotransplantation: an in vitro study.
AB  - Pig-to-human xenotransplantation faces the problem of hyperacute graft rejection
      due to the presence of human naturally occurring antibodies against the
      disaccharide Galalpha1-3Gal (anti-Gal antibodies) expressed on pig endothelium.
      Antibody-mediated complement activation is usually referred to as classical
      pathway activation. In this study we examined if the alternative complement
      pathway is also directly activated through anti-Gal antibodies or if the
      classical pathway is indispensable. We therefore developed a hemolysis test with
      rabbit erythrocytes (E), which have an activating surface for the alternative
      complement pathway and express abundant amounts of Galalpha1-3Gal, and used this
      assay in addition to the standard complement tests CH50 and AP50. In this rabbit
      E CH50 (RECH50) assay we were able to study activation of both major complement
      pathways simultaneously. FACS analysis was used to trace complement and antibody
      deposition on rabbit E. Anti-Gal depletion of human serum by immunoabsorption
      revealed a 65% reduction of rabbit E hemolysis in the RECH50 test (value before
      absorption: 28 +/- 5.8, after absorption: 9.9 +/- 2.8, P<0.001), but only a 35%
      reduction of lysis in the AP50 test (AP50 before 11.3 +/- 2.1, after 7.4 +/- 2.0,
      P<0.002). Repletion with purified anti-Gal fully restored hemolysis in both
      assays. Serum depleted of Clq showed a reduced lysis of rabbit E as compared to
      normal human serum; this effect increased with higher serum dilutions. The
      reciprocal picture, i.e. less effect on hemolysis with increasing dilution, was
      seen with factor D depleted serum. Comparison of the RECH50 values with the AP50
      values revealed an 8.4-fold increase of lysis in the RECH50 test, in which both
      complement pathways are running. By FACS analysis, complement deposition on
      rabbit E was determined and components of the classical pathway were found,
      especially in sera where the alternative pathway was disrupted. We conclude that
      in our model anti-Gal induce lysis via both classical and alternative complement
      pathways, but that the alternative pathway activation is of minor importance. In
      addition, we saw that with higher serum dilutions, the classical pathway (i.e.
      anti-Gal-mediated lysis) takes a predominant role in lysing the rabbit E. As anti
      Gal-mediated activation of the alternative complement cascade seems of minor
      importance based on our results, and as there are only few surfaces in
      transplanted organs that would favor the alternative pathway to be executed, the
      specific inhibition of early steps of the classical pathway appears as a
      realistic strategy in pig-to-primate xenotransplantation that-to the benefit of
      the patient-leaves the mainly anti-bacterial defense by the alternative pathway
      intact.

PMID- 12180843
TI  - Islet xenograft rejection in absence of CD8+ T cells does not require either
      interferon-gamma or interleukin-5.
AB  - We recently demonstrated that interleukin-5 and eosinophils mediate rejection of
      skin allografts when CD8+ T cell-dependent and Th1-type CD4+ T cell-dependent
      pathways are not functional. The purpose of this study was to determine whether a
      similar mechanism might be operative during rejection of rat islet xenografts in
      mice. First, we observed that eosinophils indeed infiltrate rejected islet grafts
      together with CD4+ and CD8+ T cells. CD8+ T cell depletion significantly enhanced
      graft survival and a further prolongation of islet function was obtained in
      combination with interferon-gamma neutralization. However, islet rejection
      characterized by prominent eosinophil and macrophage infiltration still occurred
      in this setting. Although eosinophil infiltrates were dramatically reduced in
      interleukin-5 deficient mice, the ability of these animals to reject islet
      xenografts under CD8+ T cell depletion and interferon-gamma neutralization was
      similar to that of wild-type mice. We conclude that in absence of CD8+ T cells
      and interferon-gamma, macrophages, but not eosinophils, mediate rejection of rat
      to-mouse islet xenografts.

PMID- 12180842
TI  - Virus safety in xenotransplantation: first exploratory in vivo studies in small
      laboratory animals and non-human primates.
AB  - For xenotransplantation, the transplantation of animal cells, tissues and organs
      into human recipients, to date, pigs are favored as potential donors. Beside
      ethical, immunological, physiological and technical problems, the microbiological
      safety of the xenograft has to be guaranteed. It will be possible to eliminate
      all of the known porcine microorgansims in the nearby future by vaccinating or
      specified pathogen-free breeding. Thus, the main risk will come from the porcine
      endogenous retroviruses (PERVs) which are present in the pig genome as proviruses
      of different subtypes. PERVs will therefore be transmitted, with the xenograft,
      to the human recipient. PERVs can infect numerous different types of human
      primary cells and cell lines in vitro and were shown to adapt to these cells by
      serial passaging on uninfected cells. Furthermore, PERVs have high homology to
      other retroviruses, such as feline leukemia virus (FeLV) or murine leukemia virus
      (MuLV), which are known to induce tumors or immunodeficiencies in the infected
      host. To evaluate the potential risk of a trans-species transmission of PERV in
      vivo, naive and immunosuppressed rats, guinea pigs and minks were inoculated with
      PERV and screened over a period of 3 months for an antibody reaction against PERV
      proteins or for the integration of proviral DNA into the genomic DNA of the
      host's cells. Furthermore, we inoculated three different species of non-human
      primates, rhesus monkey (Macaca mulatta), pig-tailed monkey (Macaca nemestrina)
      and baboon (Papio hamadryas) with high titers of a human-adapted PERV. To
      simulate a situation in xenotransplantation, the animals received a daily triple
      immunosuppression using cyclosporine A, methylprednisolone and RAD, a rapamycin
      derivative, presently under development by Novartis. None of the small laboratory
      animals or the non-human primates showed production of antibodies against PERV or
      evidence of integration of proviral DNA in blood cells or cells of several
      organs, 3 months after virus inoculation, despite the observation that cells of
      the animals used in the experiment were infectible in vitro. This apparent
      difference in the outcome of the in vitro and the in vivo data might be explained
      by an efficient elimination of the virus by the innate or adaptive immunity of
      the animals.

PMID- 12180844
TI  - The impact of regulatory policy on the development of somatic cell therapies in
      the United States.
AB  - Cellular therapies offer new promise for the treatment of a variety of diseases.
      In order to protect patients and donors, the Food and Drug Administration in the
      USA has been developing specific regulations. These have undergone several
      iterations, however, a broad-based strategy has recently emerged. These proposals
      are reviewed and their impact on academic institutions is assessed.

PMID- 12180845
TI  - Gene therapy in transplantation.
AB  - Gene transfer and gene therapy represent a relatively new field that has grown
      and expanded enormously in the last 5-10 years. The application of gene transfer
      and gene medicines to transplantation is currently in its infancy. Consideration
      for gene medicines in transplantation requires delivery of vectors, either to the
      graft or to the immune system. Delivery of vectors to the graft provides a choice
      of potential immunologic targets including: costimulatory signals; inhibitory
      cytokines; adhesion molecules; and molecules relating to apoptosis. In addition,
      non-immunologic targets, that increase graft protective mechanisms by reducing
      ischemic and immunologic damage, represent significant targets for gene transfer.
      Delivery of vectors to the immune system includes potential targets to modify the
      immune system, and results in tolerance. Other considerations for gene therapy
      include the development of additional technologies, such as gene conversion or
      transgenesis coupled with xenotransplantation, which may provide genetically
      modified organs. Another important aspect of gene transfer relates to regulation
      of the transgene expression. A variety of issues concerning innate immunity,
      adaptive immunity, response to vector components, response to transgene products,
      and entry of vectors into the antigen presentation and processing pathway require
      further investigation and refinement of approaches. Lastly, regulatable promoters
      and the understanding of their interaction with individual cells, tissues and
      organs, and their interaction with innate and adaptive immunity, are of paramount
      importance to improving the efficacy and utility of gene transfer. There is no
      doubt that there is much exciting basic and translational science to be
      accomplished in the next decade in order to solve these potential barriers and
      advance gene medicines into the clinical realm in transplantation.

PMID- 12180846
TI  - Cardiac tissue engineering.
AB  - Recent progress in implantations of differentiated cardiac and non-cardiac cells
      as well as adult stem cells into the heart suggests that the irreversible loss of
      viable cardiac myocytes that occurs during myocardial infarction can be at least
      partly substituted. We evaluated an alternative approach by reconstituting
      cardiac tissue grafts in vitro and implanting them as spontaneously and
      coherently contracting tissues. For this purpose we have optimized a method to
      generate ring-shaped three-dimensional engineered heart tissue (EHT) in vitro
      from neonatal rat cardiac myocytes. When subjected to isometric force
      measurements in organ baths, electrically stimulated EHTs exhibit a Frank
      Starling behavior, a positive inotropic response to increases in extracellular
      calcium, a positive inotropic and lusitropic response to isoprenaline, and a
      negative inotropic response to the muscarinic agonist carbachol ('accentuated
      antagonism'). Twitch tension under maximal calcium amounts to 1-2 mN/ mm2.
      Importantly, passive (resting) tension is low, yielding a ratio of active/passive
      tension of approximately 1.5 under basal and 14 under maximal calcium.
      Morphologically, EHTs represent a highly interconnected three-dimensional network
      of cardiac myocytes resembling loose cardiac tissue with a high fraction of
      binucleated cardiac myocytes, strong eosin staining and elongated centrally
      located nuclei. Electron microscopy demonstrated well developed sarcomeric
      structures, T-tubules, SR vesicles, T-tubule-SR-junctions, all types of
      intercellular connective structures, and a basement membrane. Thus, EHTs comprise
      functional and morphological properties of intact, ventricular myocardium. First
      implantation experiments of EHTs in the peritoneum of Fischer 344 rats showed
      that EHTs survived for at least 14 days, maintained a network of differentiated
      cardiac myocytes, and were strongly vascularized. Thus, EHTs may serve as
      material for a novel tissue replacement approach.

PMID- 12180848
TI  - The relationship between surgeon and basic scientist.
AB  - Basic science research has always been the cornerstone of a solid academic
      career, even for surgeons. In the past, many cardiothoracic and cardiovascular
      surgeons have used the large animal laboratory to design surgical operations,
      refine extracorporeal circulation, improve myocardial protection or simply
      validate clinical concepts. Today, funding for large animal research has almost
      disappeared. The basic science areas of 'cellular, molecular, genomics or gene
      therapy' must be involved to be considered for national or even local funding.
      This endeavor requires a new generation of surgical scientists and perhaps even
      more importantly, a new environment for the performance of such research.
      Academic surgery does not exist without active and long-standing commitment to
      research. Clinical research focusing on patient outcome remains an important task
      of the academic surgeon but this paper will focus on the relationship between
      surgeons and basic scientists and shall concentrate primarily on translational
      research and its challenge now and in the future. The collaboration between basic
      scientist and clinician is more essential than ever, because the society still
      optimally rewards science that has potential clinical applicability [1]. Even
      within surgical departments, active support and very close contact with PhDs can
      be essential for the clinical faculty members to be productive, using cellular
      and molecular techniques. In cardiovascular medicine and biology, there is a
      great potential to prevent or treat diseases with these techniques. The potential
      to modify ischemia-reperfusion, inflammation, angiogenesis, restenosis, organ
      tolerance or cardiomyocyte transplantation to remodel ventricles will be
      accomplished by a better understanding of cardiovascular biology. Surgeons must
      plan for a speciality that may look quite different in the next future.

PMID- 12180847
TI  - Efficient in vitro transduction of epithelial cells and keratinocytes with
      improved adenoviral gene transfer for the application in skin tissue engineering.
AB  - The adenovirus-mediated transfer of therapeutic genes into keratinocytes may be a
      useful approach to treat several skin diseases or to improve the graft take of in
      vitro generated skin equivalents used for wound coverage. However, in contrast to
      many other tissues, keratinocytes are relatively difficult to transduce by
      adenoviral vectors. To achieve high efficiency of adenoviral transduction into
      epithelial cells we investigated the effects of the polycation polybrene on the
      infection process. The human (HaCaT, A549) and rat (NBT II, MHICI) epithelial
      cell lines, as well as human and rat primary keratinocytes, were transduced with
      recombinant Ad(beta)-gal adenovirus, encoding for the reporter gene E. coli beta
      galactosidase, in the presence of various polybrene concentrations. We determined
      the amount of beta-gal positive cells by X-gal staining and the beta-gal
      expression by ONPG-assay after 24 h. In all tested human and rat epithelial cell
      lines, as well as in human and rat primary keratinocytes, the addition of
      polybrene during adenoviral transduction of Ad(beta)-gal resulted in a marked
      increase of beta-gal positive cells and beta-gal protein expression. The efficacy
      of polybrene showed a clear dose dependency. The improvement of adenoviral gene
      transfer into various types of human and rat epithelial cells by polybrene allows
      us to reduce the amount of recombinant virus particles resulting in a decreased
      inflammation induced by this therapeutic agent. In addition, the efficient
      transduction and expression with enhanced adenoviral transfer of therapeutic
      genes into primary keratinocytes provides a powerful tool for analysing the
      functions and the regulation of a gene of interest in vitro.

PMID- 12180849
TI  - The choice of the appropriate colours in subjects boosts performance and
      satisfaction.

PMID- 12180850
TI  - Signal transduction and co-stimulatory pathways.
AB  - Using specific cell surface receptors lymphocytes continuously sample their
      environment. Maturation of the immune system and initiation of a specific immune
      response rely on an array of extracellular cues that elicit complex intracellular
      biochemical signals. Essential molecules involved in signal transduction from
      immunoreceptors have emerged. After immunoreceptor engagement a core signaling
      complex is assembled comprising cytoplasmic immunoreceptor chains, kinases of the
      Src and ZAP70 families and various cytoplasmic and transmembrane adaptor
      molecules. Further effectors nucleate onto this complex evoking the
      characteristic responses of lymphocyte activation. Successful maturation of T
      cells into effector cells relies on the presence of a persistent stimulus
      presented in an appropriate extracellular environment. Encounter of MHC presented
      antigenic peptides and their cognate T cell receptors (TCRs) results in the
      formation of a nanometer intercellular gap between T cells and antigen presenting
      cells, which is now commonly referred to as the immunological synapse. The
      synapse is believed to sustain persistent TCR engagement. Its formation requires
      massive changes in T cell cytoskeletal architecture which essentially relies on
      signals provided by costimulatory molecules. The well orchestrated interplay
      between TCR and costimulatory signals decides about successful immune response
      and tolerance induction or immune failure and autoimmunity.

PMID- 12180851
TI  - Bag-1 up-regulation in anti-CD4 mAb-treated allo-activated T cell confers
      resistance to activation-induced cell death (AICD).
AB  - The non-depleting anti-CD4 monoclonal antibody (mAb) RIB5/2 is a powerful inducer
      of tolerance to major histocompatibility complex (MHC)-incompatible allografts in
      rat recipients. The unresponsiveness induced is characterized by the persistence
      (over 300 days) of donor-reactive regulatory T cells within the graft. We applied
      differential-display reverse-transcription polymerase chain reaction (RT-PCR) to
      identify differences at the mRNA level between graft-infiltrating cells of anti
      CD4 mAb-treated and non-treated control rats at day 5 after kidney
      transplantation. A 550-bp DNA fragment appearing only in anti-CD4 mAb-treated
      rats is identical with the anti-apoptotic protein Bag-1. A further investigation
      of Bag-1 expression during mixed lymphocyte reactions (MLR) revealed a three-four
      fold up-regulation of Bag-1 mRNA expression in anti-CD4 mAb-treated allogeneic
      cultures. Bag-1 up-regulation is associated with higher protection against
      apoptosis of anti-CD4 mAb-treated cultures. Application of antisense
      oligonucleotides specific for Bag-1 leads to both a reduction in Bag-1 expression
      and sensibility against apoptosis. Thus, the expression of Bag-1 in anti-CD4 mAb
      treated alloreactive T cells conferred resistance against apoptosis, which may
      contribute to the long-term survival of tolerance-mediating T cells in vivo.

PMID- 12180852
TI  - The role of glycosyl phosphatidyl inositol (GPI)-anchored cell surface proteins
      in T-cell activation.
AB  - Glycosylphosphatidylinositol (GPI)-anchored cell surface proteins are widely
      expressed in tissues, including cells of immunohematopoietic origin. Cross
      linking of GPI-linked proteins on T lymphocytes, such as Thy-1 (CD90), Ly-6 A/E,
      CD48, CD59 and others, induces T-cell mitogenesis. Similar to cross-linking with
      T-cell receptor (TcR)-specific antibodies, ligation of GPI-anchored proteins
      induces an intracellular flux of calcium, an up-regulation of activation
      associated cell surface proteins and the elaboration of growth-promoting
      lymphokines. These events are dependent on p56(lck)-mediated tyrosine
      phosphorylation of substrates. GPI-linked proteins are constitutively clustered
      in sphingolipid-rich membrane domains. Actin-driven rearrangements of the
      cytoskeleton are probably responsible for the physical approximation of TcR and
      GPI-anchored proteins in mature immunological synapses. Functionally, GPI-linked
      proteins can supplant for signal I and productively collaborate with CD28 to
      fully activate T cells.

PMID- 12180853
TI  - The role of matrix metalloproteinases in the activation of mesangial cells.
AB  - Mesangial cells play a prominent role in renal inflammatory disorders, especially
      in IgA nephropathy. This disease represents the most common form of
      glomerulonephritis that eventually leads to progressive kidney failure requiring
      renal replacement therapy. In kidney transplants, IgA nephropathy displays a high
      recurrence rate in the order of 50%. Increased cell proliferation rates and
      extracellular matrix (ECM) accumulation are crucial targets in the therapy of
      glomerulonephritis, including IgA nephropathy. The active role of matrix
      metalloproteinases (MMP) in the regulation of these two features is rapidly
      emerging. We studied a model of a specific type of mesangial cell-mediated
      glomerular inflammation, such as experimental mesangial proliferative
      glomerulonephritis and cultured proliferating mesangial cells. In addition, these
      tools allowed us to evaluate a new therapeutic strategy based on MMP inhibition.
      Inhibition of MMP activity and synthesis by antisense technology and by a
      synthetic inhibitor in vitro, successfully reverted the inflammatory mesangial
      cell phenotype to the physiologically existing resting state. In vivo, a
      hydramate-based MMP inhibitor attenuated excess mesangial cell proliferation and
      ECM accumulation in anti-Thy1.1 nephritis. The anti-proliferative effect was
      achieved by the induction of cell cycle arrest followed by apoptosis, mediated by
      the induction of p53, p21 and bax, but not by the Fas/FasL pathway. In
      conclusion, MMP inhibitors provide a new approach to the therapy of inflammation
      probably even beyond the field of renal disorders.

PMID- 12180854
TI  - Development of glutamatergic synapses in the rat retina: the postnatal expression
      of ionotropic glutamate receptor subunits.
AB  - We examined the distribution of the AMPA glutamate receptor subunits GluR1 to
      GluR4, of the kainate receptor subunits GluR6/7 and KA2, and of the glutamate
      receptor subunits delta1/2, during postnatal development of the rat retina by
      immunocytochemistry and light microscopy using receptor subunit specific
      antisera. The various ionotropic glutamate receptor subunits were expressed early
      in postnatal rat retina, and most of the subunits, with the exception of
      delta1/2. were found in both synaptic layers of rat retina. The glutamate
      receptor subunits studied showed differences in their time of appearance, their
      spatial distribution patterns, and in their expression levels in the developing
      rat retina. Interestingly, most of the AMPA receptor subunits were expressed
      earlier than the kainate receptor subunits in the two synaptic layers of the
      retina, indicating that AMPA glutamate receptors play an important role in early
      postnatal glutamatergic synaptic transmission. We also studied the
      ultrastructural localization of the AMPA glutamate receptor subunits GluR1 to
      GluR4 by immunocytochemistry and electron microscopy in the inner plexiform layer
      of the mature rat retina. Most of the subunits were found postsynaptic to the
      ribbon synapses of OFF-cone, ON-cone, and rod bipolar cells. The results of this
      study suggest an involvement of ionotropic glutamate receptors in processes of
      synaptic maturation and the formation of synaptic circuitries in the developing
      plexiform layers of the retina. Furthermore, AMPA and kainate receptors play a
      role in synaptic processing and in the development of both the scotopic and
      photopic pathways in the rat retina.

PMID- 12180855
TI  - Differential distributions of red-green and blue-yellow cone opponency across the
      visual field.
AB  - The color vision of Old World primates and humans uses two cone-opponent systems;
      one differences the outputs of L and M cones forming a red-green (RG) system, and
      the other differences S cones with a combination of L and M cones forming a blue
      yellow (BY) system. In this paper, we show that in human vision these two systems
      have a differential distribution across the visual field. Cone contrast
      sensitivities for sine-wave grating stimuli (smoothly enveloped in space and
      time) were measured for the two color systems (RG & BY) and the achromatic (Ach)
      system at a range of eccentricities in the nasal field (0-25 deg). We spatially
      scaled our stimuli independently for each system (RG, BY, & Ach) in order to
      activate that system optimally at each eccentricity. This controlled for any
      differential variations in spatial scale with eccentricity and provided a
      comparison between the three systems under equivalent conditions. We find that
      while red-green cone opponency has a steep decline away from the fovea, the loss
      in blue-yellow cone opponency is more gradual, showing a similar loss to that
      found for achromatic vision. Thus only red-green opponency, and not blue-yellow
      opponency, can be considered a foveal specialization of primate vision with an
      overrepresentation at the fovea. In addition, statistical calculations of the
      level of chance cone opponency in the two systems indicate that selective S cone
      connections to postreceptoral neurons are essential to maintain peripheral blue
      yellow sensitivity in human vision. In the red-green system, an assumption of
      cone selectivity is not required to account for losses in peripheral sensitivity.
      Overall, these results provide behavioral evidence for functionally distinct
      neuro-architectural origins of the two color systems in human vision, supporting
      recent physiological results in primates.

PMID- 12180856
TI  - The pupillary and ciliary components of the cat Edinger-Westphal nucleus: a
      transsynaptic transport investigation.
AB  - The distribution of preganglionic motoneurons supplying the ciliary ganglion in
      the cat was defined both qualitatively and quantitatively. These cells were
      retrogradely labeled directly, following injections of wheat germ agglutinin
      conjugated to horseradish peroxidase (WGA-HRP) into the ciliary ganglion, or were
      transsynaptically labeled following injections of WGA into the vitreous chamber.
      Almost half of the cells are distributed rostral to the oculomotor nucleus, both
      in and lateral to the anteromedian nucleus. Of the remaining preganglionic
      motoneurons, roughly 20% of the total are located dorsal to the oculomotor
      nucleus. Strikingly few of these neurons are actually found within the Edinger
      Westphal nucleus proper. Instead, the majority are found in the adjacent
      supraoculomotor area or along the midline between the two somatic nuclei. An
      additional population, roughly 30% of the total, is located ventral to the
      oculomotor nucleus. This study also provides evidence for a functional
      subdivision of this preganglionic population. Pupil-related preganglionic
      motoneurons were transsynaptically labeled by injecting WGA into the anterior
      chamber, while lens-related preganglionic motoneurons were transsynaptically
      labeled by injecting WGA into the ciliary muscle. The results suggest that the
      pupil-related preganglionic motoneurons, that is, those controlling the iris
      sphincter pupillae muscle, are located rostrally, in and lateral to the
      anteromedian nucleus. In contrast, lens-related preganglionic motoneurons, that
      is, those controlling the ciliary muscle are particularly prevalent caudally,
      both dorsal and ventral to the oculomotor nucleus. Thus, the cat intraocular
      muscle preganglionic innervation is spatially organized with respect to function,
      despite the dispersed nature of its distribution.

PMID- 12180857
TI  - Residual eye-movements in macaque and their effects on visual responses of
      neurons.
AB  - We recorded continuously, with high precision, the positions of the eyes in
      anesthetized macaque monkeys prepared for physiological recording. Most
      recordings were made after the infusion of muscle relaxant to immobilize the
      eyes; in some cases we also were able to record eye position for periods before
      the eyes were immobilized. In all monkeys, the eyes moved continuously by as much
      as 0.5 deg over a 10-min sampling period. The average distance moved was
      proportional to the square root of the sampling period, as would be expected from
      a random walk. The movements had three distinct components: slow drifts, and two
      rhythms driven by the pulse and respiration. The rhythmic movements occurred only
      under paralysis: they were not discernible in measurements made before the
      infusion of muscle relaxant. The movements of the eye in the paralyzed animal can
      have substantial effects on the measured physiological characteristics of
      neurons. For excursions in the midrange of those we observed, a neuron's
      sensitivity to a spatial frequency of 10 cycle/deg might be underestimated by as
      much as a factor of three, depending on the method by which responses were
      averaged. We show how the effects of eye-movements can be mitigated by
      appropriate data analysis.

PMID- 12180858
TI  - Optical imaging of orientation and ocular dominance maps in area 17 of cats with
      convergent strabismus.
AB  - Strabismus (or squint) is both a well-established model for developmental
      plasticity of the brain and a frequent clinical symptom. While the layout and
      topographic relationship of functional domains in area 17 of divergently
      squinting cats has been analyzed extensively in recent years (e.g. Lowel et al.,
      1998), functional maps in convergently squinting animals have so far not been
      visualized with comparable detail. We have therefore investigated the functional
      organization of area 17 in adult cats with a surgically induced convergent squint
      angle. In these animals, visual acuity was determined by both behavioral tests
      and recordings of visual evoked potentials, and animals with comparable acuities
      in both eyes were selected for further experiments. The functional layout of area
      17 was visualized using optical imaging of intrinsic signals. Monocular iso
      orientation domains had a patchy appearance and their layout was different for
      left and right eye stimulation, so that segregated ocular dominance domains could
      be visualized. Iso-orientation domains exhibited a pinwheel-like organization, as
      previously described for normal and divergently squinting cats. Mean pinwheel
      density was the same in the experimental and control animals (3.4 pinwheel
      centers per mm2 cortical surface), but significantly (P < 0.00001) higher than
      that reported previously for normal and divergently squinting cats (2.7/mm2). A
      comparison of orientation with ocular dominance maps revealed that iso
      orientation domains were continuous across the borders of ocular dominance
      domains and tended to intersect these borders at steep angles. However, in
      contrast to previous reports in normally raised cats, orientation pinwheel
      centers showed no consistent topographical relationship to the peaks of ocular
      dominance domains. Taken together, these observations indicate an overall
      similarity between the functional layout of orientation and ocular dominance maps
      in area 17 of convergently and divergently squinting cats. The higher pinwheel
      densities compared with previous reports suggest that animals from different gene
      pools might generally differ in this parameter and therefore also in the space
      constants of their cortical orientation maps.

PMID- 12180860
TI  - Mapping photoreceptor and postreceptoral labelling patterns using a channel
      permeable probe (agmatine) during development in the normal and RCS rat retina.
AB  - The aim of this study was to determine whether agmatine, a channel permeable
      probe, can identify photoreceptor dysfunction in the Royal College of Surgeons
      (RCS) retina at an earlier stage to that shown by apoptosis or anatomical
      markers, and also characterize the neurochemical development of the inner retina
      in the normal and degenerating rat. We used isolated retinas at different ages
      incubated in physiological media containing agmatine. Subsequently, postembedding
      immunocytochemistry was used to determine the number of labelled photoreceptors
      and the labelling pattern within postreceptoral neurons. Agmatine labelling
      patterns revealed a sequential development of retinal neurons beginning at
      postnatal day (PND) 11/12 with most horizontal cells, a few ganglion and amacrine
      cells, showing a strong signal. The neurochemical development progressed rapidly,
      and reflects to a large part the known distribution of glutamate receptors, with
      inner nuclear labelling being evident by PND14, continuing with the same pattern
      of labelling in adulthood for the control retina. The RCS retina showed markedly
      reduced agmatine labelling in the inner retina at PND20. A rapid increase in
      photoreceptor AGB labelling was evident during the degeneration phase. Multiple
      samples at PND14 and PND16 confirmed a significant increase of labelled
      photoreceptors in the RCS retina.

PMID- 12180859
TI  - Synaptic inputs of class III and class V interneurons in the cat pulvinar
      nucleus: differential integration of RS and RL inputs.
AB  - We previously reported that two types of visual thalamic interneurons (class III
      and class V) could be distinguished by the presence or absence of the enzyme
      brain nitric oxide synthase (bNOS; Bickford et al., 1999). In the present study,
      we found that further immunocytochemical characterization can be used to isolate
      class V and class III neurons: class V neurons express GABA and bNOS but not the
      calcium binding protein calbindin, whereas class III neurons express GABA and
      calbindin, but not bNOS. By pairing staining for bNOS or calbindin with staining
      for GABA, we were able to distinguish class III and class V neurons, thereby
      allowing us to characterize the synaptic inputs to these two interneuron
      populations within the cat pulvinar nucleus. We found class III and class V
      interneurons participate in distinctly different circuitries. Class III cells
      receive the majority of their input from large terminals with round vesicles (RL
      profiles, that presumably originate from cortical layer V) while class V cells
      receive all of their input from small terminals with round vesicles (RS profiles,
      that presumably originate from cortical layer VI). These two types of
      interneurons also target different regions of the dendritic arbors of
      thalamocortical cells; class III cells contact large caliber (presumably
      proximal) thalamocortical dendrites within glomeruli, while class V cells contact
      the small caliber (presumably distal) thalamocortical cell dendrites within the
      extraglomerular neuropil. Thus, a dual inhibitory system exists within the visual
      thalamus that integrates different types of corticothalamic input and targets
      distinct regions of thalamocortical cell dendritic arbors.

PMID- 12180861
TI  - Spatial-chromatic interactions in C-type horizontal cells of the turtle (Mauremys
      caspica) retina.
AB  - Horizontal cells are second-order retinal neurons that play a key role in spatial
      information processing. In some cold-blooded vertebrates such as turtles, a
      subtype of these cells, the chromaticity horizontal cells exhibit color-opponent
      responses and therefore are considered to be important also for color information
      processing. To reveal spatial and color interactions, the receptive-field
      properties of Red/Green and Yellow/Blue chromaticity horizontal cells in the
      retina of the turtle Mauremys caspica were studied by intracellular recordings
      from the everted eyecup preparation. We found that the polarity of the
      photoresponses depended not only upon the wavelength and intensity of the
      stimulus, but also upon its spatial configuration. Thus, a hyperpolarizing
      photoresponse that was elicited by full-field stimulation with bright light of
      wavelength close to the "neutral" one was reversed in polarity to a pure
      depolarizing one when a small spot or a thin annular pattern were used for
      stimulation. This finding could not be explained either by different balances
      between depolarizing and hyperpolarizing inputs to different cells or by stray
      light that effectively reduced the light intensity in the center of the small
      spot. Rather, it was found that the depolarizing and hyperpolarizing components
      were characterized by different receptive-field size and that these differences
      could account for the dependency of response polarity upon the spatial pattern of
      the stimulus. These findings indicate that color information processing in turtle
      C-type horizontal cells is a complex process that depends upon the wavelength and
      intensity of the light stimulus as well as upon its spatial properties.

PMID- 12180863
TI  - Are primate lateral geniculate nucleus (LGN) cells really sensitive to
      orientation or direction?
AB  - There is considerable controversy over the existence of orientation and direction
      sensitivity in lateral geniculate nucleus (LGN) neurons. Claims for the existence
      of these properties often were based upon data from cells tested well beyond
      their peak spatial frequencies. The goals of the present study were to examine
      the degree of orientation and direction sensitivity of LGN cells when tested at
      their peak spatial and temporal frequencies and to compare the tuning properties
      of these subcortical neurons with those of visual cortex. For this investigation,
      we used conventional extracellular recording to study orientation and direction
      sensitivities of owl monkey LGN cells by stimulating cells with drifting
      sinusoidal gratings at peak temporal frequencies, peak or higher spatial
      frequencies, and moderate contrast. A total of 110 LGN cells (32 koniocellular
      cells, 34 magnocellular cells, and 44 parvocellular cells) with eccentricities
      ranging from 2.6 deg to 27.5 deg were examined. Using the peak spatial and
      temporal frequencies for each cell, 41.8% of the LGN cells were found to be
      sensitive to orientation and 19.1% were direction sensitive. The degree of bias
      for orientation and direction did not vary with eccentricity or with cell class.
      Orientation sensitivity did, however, increase, and in some cases orientation
      preferences changed, at higher spatial frequencies. Increasing spatial frequency
      had no consistent effect on direction sensitivity. Compared to cortical cell
      orientation tuning, the prevalence and strength of LGN cell orientation and
      direction sensitivity are weak. Nevertheless, the high percentage of LGN cells
      sensitive to orientation even at peak spatial and temporal frequencies reinforces
      the view that subcortical biases could, in combination with activity-dependent
      cortical mechanisms and/or cortical inhibitory mechanisms, account for the much
      narrower orientation and direction tuning seen in visual cortex.

PMID- 12180862
TI  - Topographic map reorganization in cat area 17 after early monocular retinal
      lesions.
AB  - Neither discrete peripheral retinal lesions nor the normal optic disk produces
      obvious holes in one's percept of the world because the visual brain appears to
      perceptually "fill in" these blind spots. Where in the visual brain or how this
      filling in occurs is not well understood. A prevailing hypothesis states that
      topographic map of visual cortex reorganizes after retinal lesions, which "sews
      up" the hole in the topographic map representing the deprived area of cortex
      (cortical scotoma) and may lead to perceptual filling in. Since the map
      reorganization does not typically occur unless retinotopically matched lesions
      are made in both eyes, we investigated the conditions in which monocular retinal
      lesions can induce comparable map reorganization. We found that following
      monocular retinal lesions, deprived neurons in cat area 17 can acquire new
      receptive fields if the lesion occurred relatively early in life (8 weeks of age)
      and the lesioned cats experienced a substantial period of recovery (>3 years).
      Quantitative determination of the monocular and binocular response properties of
      reactivated units indicated that responses to the lesioned eye for such neurons
      were remarkably robust, and that the receptive-field properties for the two eyes
      were generally similar. Moreover, excitatory or inhibitory binocular interactions
      were found in the majority of experimental units when the two eyes were activated
      together. These results are consistent with the hypothesis that map
      reorganization after monocular retinal lesions require experience-dependent
      plasticity and may be involved in the perceptual filling in of blind spots due to
      retinal lesions early in life.

PMID- 12180864
TI  - Finland has BSE: only Sweden 'safe'.

PMID- 12180866
TI  - Generic import risk analysis for dogs and cats.

PMID- 12180865
TI  - Screw-worm fly threat.

PMID- 12180867
TI  - United Kingdom's response to its foot-and-mouth disease (FMD) epidemic.

PMID- 12180868
TI  - Veterinary pathologists in Australia.

PMID- 12180869
TI  - A case about ethics not treatment.

PMID- 12180870
TI  - A case about ethics not treatment.

PMID- 12180871
TI  - A case about ethics not treatment.

PMID- 12180872
TI  - Lack of veterinary practitioners in rural areas.

PMID- 12180873
TI  - Noninvasive estimation of cardiac systolic function using continuous-wave Doppler
      echocardiography in dogs with experimental mitral regurgitation.
AB  - OBJECTIVE: To evaluate the feasibility of noninvasive estimation of cardiac
      systolic function using transthoracic continuous-wave Doppler echocardiography in
      dogs with mitral regurgitation. PROCEDURE: Seven mongrel dogs with experimental
      mitral regurgitation were used. Left ventriculography and measurement of
      pulmonary capillary wedge pressure were performed under inhalational anaesthesia.
      A micromanometer-tipped catheter was placed into the left ventricle and
      transthoracic echocardiography was carried out. The peak rate of left ventricular
      pressure rise (peak dP/dt) was derived simultaneously by continuous-wave Doppler
      and manometer measurements. The Doppler-derived dP/dt was compared with the
      catheter-measured peak dP/dt in the dogs. RESULTS: Classification of the severity
      of mitral regurgitation in the dogs was as follows: 1+, 2 dogs; 2+, 1 dog; 3+, 2
      dogs; 4+, 1 dog; and not examined, 1 dog. We were able to derive dP/dt from the
      transthoracic continuous-wave Doppler echocardiography in all dogs. Doppler
      derived dP/dt had a significant correlation with the catheter-measured peak dP/dt
      (r = 0.90, P < 0.0001). CONCLUSION: It was demonstrated that transthoracic
      continuous-wave Doppler echocardiography is a feasible method of noninvasive
      estimation of cardiac systolic function in dogs with experimental mitral
      regurgitation and may have clinical usefulness in canine patients with
      spontaneous mitral regurgitation.

PMID- 12180874
TI  - Dicoumarol toxicity in cattle associated with ingestion of silage containing
      sweet vernal grass (Anthoxanthum odoratum).
AB  - A diagnosis of dicoumarol toxicity in a herd of Friesian cattle was made
      following investigation of the deaths of three mature cows and eleven yearling
      heifers. Affected stock had been fed wrapped, bailed silage containing
      approximately 90% sweet vernal grass (Anthoxanthum odoratum). Sweet vernal grass
      contains coumarin, which can be converted to dicoumarol, a vitamin K antagonist,
      through the action of moulds. Most deaths were preceded by lethargy, severe
      anaemia and subcutaneous and internal haemorrhage. Dicoumarol toxicosis was
      suspected based on clinical signs, necropsy findings and prolonged prothrombin
      and activated partial thromboplastin times. Dicoumarol analysis of blood from
      affected animals and silage confirmed the diagnosis. Activated partial
      thromboplastin time Haemoglobin Packed cell volume Prothrombin time Red cell
      count

PMID- 12180875
TI  - Unusual ovarian activity in a mare preceding the development of an ovarian
      granulosa cell tumour.
AB  - An 8-year-old mare, with a foal at foot, was inseminated on foal heat with frozen
      semen, with the resultant pregnancy lost between days 34 and 41. The right ovary
      developed a large anovulatory follicle that was non-responsive to multiple doses
      of ovulating agents. The follicle eventually appeared to luteinise, although
      plasma progesterone concentrations did not reflect this. Another follicle
      developed, responded to GnRH and resulted in a pregnancy from frozen semen that
      went to term with a healthy foal. When the mare was examined after foaling, the
      structure on the right ovary appeared to be a granulosa cell tumour; the left
      ovary was smaller than normal and non-functional. Surgical removal of the right
      ovary before increasing photoperiod resulted in a return to function of the left
      ovary and a pregnancy to frozen semen on the second cycle following removal.
      Figures showing concentrations of inhibin, progesterone, androstenedione,
      oestradiol and testosterone are presented for this entire period. Unusual ovarian
      activity in the mare might be a prelude to the development of a granulosa cell
      tumour.

PMID- 12180876
TI  - Clinical skills and knowledge used by veterinary graduates during their first
      year in small animal practice.
AB  - OBJECTIVE: To determine the clinical skills and areas of knowledge used by
      veterinarians in small animal practice during their first year after graduation
      and the degree of assistance and supervision they received while developing these
      skills. DESIGN: A postal survey was sent in December 1999 to 59 veterinarians who
      completed their training at Murdoch University in December 1998. PROCEDURE: The
      first part of the survey asked for information on veterinary work patterns since
      leaving university. The second part consisted of a list of diagnostic and
      therapeutic skills of varying complexity and the graduates were asked to indicate
      whether they had used these skills in practice and whether they had been assisted
      or supervised while doing them. The respondents were also asked if they had had
      the opportunity to practise these skills as undergraduates at university or
      during extramural experience. In the third part the areas of knowledge used in
      practice were assessed by analysis of a series of consecutive cases. RESULTS:
      Forty replies were received but since three graduates had done no small animal
      work the analysis of the skills section is based on 37 responses. Thirty
      graduates supplied information on 994 canine cases and 308 feline cases. The
      distribution of the mean work time was dogs and cats 69%, horses 13%, farm
      animals 11%, birds 3% and others 4%. Skills used by over 90% of graduates
      included general anaesthesia, examination of the tympanic membrane, taking and
      interpreting an abdominal radiograph, catheterising a male cat, fine needle
      aspiration of a mass, neutering dogs and cats, tooth scaling and extraction and
      treating an aural haematoma. The survey also identified the opportunities for
      undergraduates to practise some of these skills during extramural experence and
      the extent of assistance given to new graduates during their first year in
      practice. The areas of knowledge used in over 10% of the cases included
      vaccination, anaesthesia/sedation, skin/coat problems, general advice on pet
      health, neutering and musculoskeletal diseases. CONCLUSION: Veterinarians, in
      their first year after graduation, use a wide range of complex diagnostic and
      therapeutic skills. Although many of these skills are acquired during the
      undergraduate training, a significant contribution is made by extramural
      practical work undertaken during the clinical years of the undergraduate course
      and in the first year following graduation. Practising veterinarians play an
      important role in providing opportunities and supervision for clinical training.

PMID- 12180877
TI  - Microsporidiosis in a Gouldian finch (Erythrura [Chloebia] gouldiae).
AB  - A 12-day-old nestling Gouldian finch (Erythrura [Chloebia] gouldiae) was
      presented for investigation of a mortality problem in nestling finches raised by
      Bengalese finch foster parents. On histological examination, large numbers of
      spores consistent with a microsporidian organism were present within the small
      intestinal mucosa. Electron microscopy and molecular studies (sequencing the 5'
      end of the ssu rRNA gene) further defined the organism as Encephalitozoon hellem.
      Sequence homology with other eukaryotes was determined using a BLASTN search from
      the NCBI GenBank database. The finch isolate sequences showed greater than 99%
      homology with those of previously reported human and avian isolates.

PMID- 12180878
TI  - Conservative management of minimally displaced radial fractures in three horses.
AB  - Minimally displaced, spiral, radial fractures were diagnosed in three adult
      horses. Two horses had open fractures and in one horse the fracture was closed. A
      diagnosis was made on radiographs taken 24 h, 5, and 9 days after the fracture.
      There was minimal displacement of the fracture fragments despite the considerable
      time which had elapsed between fracture and diagnosis and an unfavourable
      prognosis with internal fixation, so conservative therapy was the preferred
      method of treatment. One horse developed a sequestrum and draining sinus, which
      was treated surgically under general anaesthesia 3 months after diagnosis of the
      fracture. Other complications were minimal and transient. Two horses were being
      used for pleasure riding 12 months after fracture and one horse was pasture sound
      at 8 months.

PMID- 12180879
TI  - Hiatal hernia controversies--a review of pathophysiology and treatment options.
AB  - OBJECTIVE: To provide a detailed discussion of the aetiology and pathophysiology
      of hiatal hernia in both humans and small animals, and review current medical and
      surgical treatments. DESIGN: Review article. SUMMARY: Hiatal hernia is not
      completely understood in humans or animals. It has a complex multifactorial
      aetiology and pathophysiology. A primary disturbance of the lower oesophageal
      sphincter has not been shown in humans or animals. Knowledge of pathophysiology
      is necessary to institute appropriate treatment. Medical and/or surgical therapy
      is not indicated in asymptomatic cases. Medical treatment should be used for up
      to 1 month in stable cases of sliding hiatal hernia. Paraoesophageal hiatal
      hernias and any large sliding hiatal hernia should be considered for prompt
      surgical treatment. Surgical techniques used depend on the type of hiatal hernia
      present. Surgical treatment of hiatal hernia cases should be performed by
      experienced surgeons, and must include hiatal closure and gastropexy. The Nissen
      fundoplication procedure has been discontinued in the veterinary field due to
      poor success rates, coupled with the published view that there is a marked
      difference in pathophysiology between humans and dogs. Reported complications
      associated with the original Nissen fundoplication technique are identical in the
      human and veterinary literature. There have been no complications reported with
      use of the modified or 'floppy' Nissen fundoplication in dogs. Both oesophagopexy
      and Nissen fundoplication require further evaluation in small animals.

PMID- 12180880
TI  - Surgical removal of a fish hook from the oesophagus of a turtle.
AB  - An adult male Macquarie turtle was presented for examination after swallowing a
      fish hook. Radiographs taken to determine the position of this foreign body
      within the gastrointestinal tract revealed the fish hook lodged in the turtle's
      oesophagus. Surgical removal of the fish hook involved an approach through the
      soft tissues of the lateral neck. The turtle recovered well and was returned to
      the wild.

PMID- 12180881
TI  - An estimate of specificity for a Johne's disease absorbed ELISA in northern
      Australian cattle.
AB  - OBJECTIVE: To estimate the specificity of an absorbed enzyme-linked immunosorbent
      assay kit for Johne's disease (JD) when used in mature cattle populations
      resident in northern Australia. DESIGN: Blood samples were collected from beef
      cattle in northern Queensland, the Northern Territory and northern Western
      Australia, and from dairy cattle in northern Queensland. The specificity of a
      serological test for JD was estimated by testing the blood samples with an
      absorbed ELISA kit. Further samples were collected from cattle with positive
      ELISA results to determine the presence or absence of infection with
      Mycobacterium avium subsp paratuberculosis. PROCEDURE: During 1995 and 1996,
      blood, tissue and gut contents were collected from beef cattle at abattoirs in
      Queensland and the Northern Territory; and blood and faecal samples were
      collected from dairy cattle in herds assessed to be most at risk for JD in
      northern Queensland. The blood samples were tested using an absorbed ELISA kit.
      Tissues and gut contents from beef cattle that had positive ELISA results were
      cultured for M. avium subsp paratuberculosis, and tissues were examined
      histologically. Faecal samples from dairy cattle with positive ELISA results were
      cultured for M. avium subsp paratuberculosis. RESULTS: Estimates of specificity
      for this absorbed ELISA in mature northern Australian cattle were 98.0% (97.0 to
      98.8%, 95% CI) in beef cattle, and 98.3% (96.7 to 99.3%, 95% CI) in dairy cattle.
      CONCLUSION: Estimates of specificity in this study were lower for beef cattle
      from the Northern Territory and northern Western Australia and for dairy cattle
      from northern Queensland than those quoted from studies on cattle in southern
      Western Australia. This should be considered when serological testing using the
      JD ELISA is carried out on northern Australian cattle.

PMID- 12180882
TI  - Derivation, safety and efficacy of a Marek's disease vaccine developed from an
      Australian isolate of very virulent Marek's disease virus.
AB  - OBJECTIVE: To develop a serotype 1 Marek's disease (MD) vaccine from a very
      virulent MDV (vvMDV) pathotype and demonstrate safety and efficacy against early
      challenge with very virulent field strains in the presence of maternal antibody.
      STUDY DESIGN: Strain BH 16 was isolated and attenuated by serial cell culture
      passage. One of two cloned passages was selected for vaccine development
      following early laboratory-scale protection trials in commercial birds.
      Comparative protection trials were carded out on the BH 16 vaccine and on a CVI
      988 Rispens vaccine using commercial and SPF chickens. Challenge viruses used
      were either a low passage strain BH 16 virus, the Woodlands No. 1 strain or MPF
      57 strain of MDV. The BH 16 vaccine was back-passaged in SPF chickens six times
      and virus recovered from the final passage and the original vaccine virus were
      tested for safety. The immunosuppressive potential of the BH 16 and Rispens
      vaccines was also assessed in parallel. RESULTS: The BH 16 and Rispens vaccines
      induced comparable levels of protection when used as monovalent or multivalent
      vaccines, although protection achieved with the monovalent vaccines was lower. No
      gross tumour formation was evident in any birds receiving the BH 16 vaccine or
      bird-passaged virus, although microscopic lesions were present in 2/12 birds that
      received the bird-passaged virus. In tests for immunosuppression, there was no
      histological evidence of damage to either the bursa of Fabricius or the thymus.
      CONCLUSION: The BH 16 vaccine was shown to be safe and at least as protective as
      the Rispens vaccine against three highly virulent MD challenge viruses.

PMID- 12180883
TI  - Brain damage in sheep from penetrating captive bolt stunning.
AB  - OBJECTIVE: To determine the severity and distribution of structural changes in
      the brains of adult sheep stunned by penetrating captive bolt. PROCEDURE: The
      unconstrained heads of ten, anaesthetised, unhorned, 2-year-old Merino sheep were
      impacted at the summit of the head with a penetrating captive bolt pistol. Six
      sheep were ventilated and four received no respiratory support. Two hours after
      impact, brains from the six ventilated sheep were perfusion-fixed with 4%
      paraformaldehyde. Sixteen whole, serial coronal sections from each brain were
      stained with haematoxylin and eosin and immunohistochemically for amyloid
      precursor protein, a sensitive marker of axonal and neuronal reaction in the
      brain after trauma. Pathological changes in these brains were then quantified by
      morphometric analysis. RESULTS: Structural change in all impacted brains was a
      mixture of focal injury around the wound track and more widely distributed damage
      in the cerebral hemispheres, cerebellum and brainstem, but varied considerably in
      severity between individual sheep. All nonventilated sheep died rapidly following
      respiratory arrest. CONCLUSIONS: After penetrating captive bolt stunning, damage
      to the central reticular formation, axonal connections, and the cortical mantle
      is the likely reason for failure of respiratory control and traumatic loss of
      consciousness.

PMID- 12180884
TI  - Assessment of organoleptic postmortem inspection techniques for bovine offal.
AB  - OBJECTIVE: To evaluate organoleptic postmortem inspection techniques for bovine
      livers and kidneys. STUDY DESIGN: At Australian export abattoirs, bovine liver
      and kidneys are assessed and graded by qualified meat inspectors during normal
      operations. Over a 12-month period at a large abattoir in eastern Australia
      during 1997 and 1998, a sample of these organs was reassessed independently using
      a range of pathological and microbiological methods. Agreement between routine
      inspection and independent assessment was evaluated using methods of inter-rater
      agreement. RESULTS: A total of 944 livers and 1374 kidneys were included in the
      study. All of these organs had been classified during routine inspection. The
      authors examined 363 livers and 329 kidneys both grossly and histologically,
      including 36 livers and 14 kidneys that were also subjected to microbiological
      examination. All other organs were only examined grossly. There was only a
      moderate level of agreement between the routine and independent assessment
      methods. For livers, the percentage agreement was 80.2%, McNemar's test of
      symmetry 55.2 (3 degrees of freedom, P < 0.001) and kappa 0.63. For kidneys, the
      percentage agreement was 67.8%, McNemar's test of symmetry 9.9 (1 df, P = 0.002)
      and kappa 0.35. CONCLUSIONS: The results reinforce concerns from a number of
      authors about organoleptic postmortem inspection. Risk assessment methodologies
      offer the opportunity to modify inspection techniques in a manner that is most
      relevant to current public health concerns.

PMID- 12180885
TI  - Evaluation of d,l-ethionine as a mechanism for pancreatic islet regeneration in
      dogs.
AB  - OBJECTIVE: To determine whether induction of pancreatic necrosis and islet
      proliferation by d,l-ethionine has potential for treating dogs with beta-cell
      insufficiency. DESIGN: Eighteen mixed breed dogs of both sexes were given d,l
      ethionine at 100 mg/kg three times weekly for 2 weeks; 6 dogs were euthanased at
      2, 14 and 28 d after the last dose. METHODS: Clinical signs during administration
      and recovery were assessed. Routine biochemical analyses were performed before
      each ethionine dose and then once weekly. Faecal samples were examined weekly for
      malassimilated nutrients and blood. Blood coagulation screening tests (OSPT and
      APTT) were determined on four dogs after ethionine administration. Intravenous
      glucose tolerance tests were conducted before the first and after the last
      ethionine dose and then fortnightly. All dogs were necropsied and pancreas,
      liver, kidney and jejunum were examined microscopically. RESULTS: During
      ethionine administration all animals displayed vomiting, inappetence, diarrhoea
      (often with blood), weight loss and depression. Three dogs were euthanased
      prematurely due to severe illness, but those allowed to recover were eating and
      brighter 7 d after cessation of ethionine administration. Serum concentrations of
      TLI, amylase and lipase increased initially, then decreased, during
      administration but retumed to normal during recovery. Concentrations of ALT, ALP,
      unconjugated and conjugated bilirubin increased during administration then
      decreased slowly. Histological examination revealed hepatic lipidosis and
      necrosis, but no renal or jejunal lesions. In most dogs, faecal examination
      demonstrated increased undigested starch and muscle, as well as increased
      digested and undigested fat, during ethionine administration or early during the
      recovery period, suggesting transient malassimilation. APTT was unchanged but
      OSPT was prolonged in all dogs. There was no impairment of insulin secretion or
      glucose intolerance and C-peptide concentrations were unaffected. Immediately
      after ethionine administration there was delayed insulin degradation and by day
      43 there was evidence of increased insulin sensitivity. CONCLUSION: d,l-ethionine
      administration in dogs appeared not to interfere with insulin secretion, but
      caused clinical signs and laboratory changes indicative of pancreatic exocrine
      necrosis, severe hepatobiliary disease and transient malassimilation. Pancreatic
      and hepatic dysfunction was severe but clinical recovery occurred after ethionine
      administration ceased. The severe side-effects observed with d,l-ethionine should
      preclude its potential use for treating diabetes mellitus in dogs.

PMID- 12180886
TI  - Assessment of the potential of dogs and cats as urban reservoirs of Ross River
      and Barmah Forest viruses.
AB  - OBJECTIVE: To determine whether dogs and cats are potential reservoirs of Ross
      River (RR) and Barmah Forest (BF) viruses METHOD: Young seronegative female dogs
      and cats were experimentally exposed to the viruses using Ochlerotatus vigilax
      (Skuse) mosquitoes. RESULTS: Only one of the 10 dogs and one of the 10 cats
      exposed to RR developed neutralising antibody. None of the animals developed
      detectable viraemia or clinical signs. One dog and three cats exposed to BF
      developed neutralising antibody. In addition, a serological survey of sera
      obtained from domestic dogs and cats residing in the Brisbane region indicated
      that 23.7% and 1.3% of dogs, and 14% and 2% of cats, had neutralising antibodies
      to RR and BF respectively. CONCLUSIONS: Although dogs and cats are exposed
      naturally to these viruses, and can become infected, they are unlikely to be
      important urban reservoirs of either virus.

PMID- 12180887
TI  - Phenotypic characterisation of Australian sheep and cattle isolates of Mannheimia
      haemolytica, Mannheimia granulomatis and Mannheimia varigena.
AB  - OBJECTIVE: To perform a comprehensive phenotypic characterisation of 35 isolates
      of bacteria previously identified as haemolytic Pasteurella-Actinobacillus and
      obtained from cattle and sheep. DESIGN: The 35 isolates that had been obtained
      from Australian animals, 30 from cattle and five from sheep, were compared with
      reference strains of the five recognised species of the genus Mannheimia--M.
      haemolytica, M. glucosida, M. granulomatis, M. ruminalis and M. varigena.
      RESULTS: Thirty-four of the isolates could be confidently assigned to three
      species of the genus Mannheimia. Twenty-nine were M. haemolytica, with 25 being
      isolated from cattle and four from sheep. All but three of the bovine M.
      haemolytica were isolated from pneumonic lungs. Of the three remaining bovine M.
      haemolytica isolates, one was obtained in pure culture from a bovine milk sample
      and the other two as part of a mixed flora associated with a middle ear infection
      of a calf suffering mucosal disease. Of the four ovine M. haemolytica isolates,
      two were isolated in pure culture from milk and two, also in pure culture, from
      pneumonic lungs. Three bovine isolates were identified as M. granulomatis--one
      from a tongue abscess, one from a jaw abscess and one from a lung showing
      suppurative bronchopneumonia. Two bovine isolates were identified as M. varigena-
      one coming from an udder and the other from a spleen. The available diagnostic
      records provided no information on whether these isolates were associated with a
      disease process. The remaining isolate was obtained from an ovine tongue abscess
      and could not be assigned to a recognised species within the genus Mannheimia.
      CONCLUSION: The study represents the first time that M. haemolytica, M.
      granulomatis and M. varigena have been recognised as being present in cattle and
      sheep in Australia. Veterinary laboratories that encounter Pasteurella
      Actinobacillus-like organisms from cattle and sheep should attempt as complete a
      characterisation as possible to help improve our knowledge of the disease
      potential of these organsims.

PMID- 12180888
TI  - Comparison of infectivity of Eimeria tenella oocysts maintained at 4, 12 or 28
      degrees C for up to 10 months.

PMID- 12180889
TI  - Cattle tick (Boophilus microplus) in Victoria on horses from Queensland.

PMID- 12180890
TI  - Birth of a Banteng (Bos javanicus) calf at Western Plains Zoo after fixed time
      artificial insemination.

PMID- 12180891
TI  - Feral pigs--the time bomb.

PMID- 12180892
TI  - Cosmetics: what is their influence on the skin microflora?
AB  - Human skin has a resident, transient and temporary resident microflora. This
      article considers the possibilities of topical products influencing the balance
      of the microflora. The resident micro-organisms are in a dynamic equilibrium with
      the host tissue and the microflora may be considered an integral component of the
      normal human skin. The great majority of these micro-organisms are gram-positive
      and reside on the skin surface and in the follicles. The host has a variety of
      structures, molecules and mechanisms which restrict the transient and temporary
      residents, as well as controlling the population and dominance of the resident
      group. These include local skin anatomy, hydration, nutrients and inhibitors of
      various types. The resident microflora is beneficial in occupying a niche and
      denying its access to transients, which may be harmful and infectious. Also, the
      residents are important in modifying the immune system. In the healthy host the
      microflora causes few and temporary problems. Therefore, it is of interest that
      topical products have little or no effect on the ecology of the microflora. A
      range of mechanisms by which long-term use of cosmetics may influence the
      microflora are considered. Although the risks associated are low, it is argued
      that it is necessary to monitor these changes in ecology and use technologies of
      modeling and bioinformatics to predict outcomes, whether good, neutral or of
      concern.

PMID- 12180894
TI  - Dermatological care of the diabetic foot.
AB  - Approximately 30% of patients with diabetes mellitus will have disease-related
      dermatological problems. Dry skin can be associated with autonomic neuropathy and
      may be fragile, promoting bacterial invasion. Any potentially infected 'diabetic
      foot' must be taken seriously, and non-painful deep sepsis suspected if there is
      evidence of sensory loss. Consideration should be given to eliminating nasal
      carriage of staphylococci if recurrent superficial sepsis occurs in the presence
      of poor diabetic control. Fungal infections, both of skin and nails, are common
      but usually not serious in the absence of immunosuppression. Treatment with
      topical antifungals may need to be combined with systemic therapy for successful
      eradication. Systemic antifungal therapy should be carefully considered as
      treatment needs to be prolonged and is potentially toxic, particularly in
      individuals with diabetes mellitus who often have co-morbidities. Varicose eczema
      should be treated by physical therapies intended to improve venous return and
      prevent peripheral edema and tissue injury. Allergic dermatitis is commonly
      associated with topical treatments and other sensitizers. Many reactions are not
      apparent from history, and patch testing for sensitivity is recommended. There
      are several diabetes mellitus-specific conditions that dermatologists must be
      aware of, including, necrobiosis lipoidica diabeticorum, granuloma annulare,
      diabetic dermopathy (spotted leg syndrome or shin spots), diabetic bullae
      (bullosis diabeticorum), and limited joint mobility and waxy skin syndrome.
      Ulceration, due to varying combinations of peripheral vascular disease and
      sensory neuropathy, is the province of the specialist team dealing with the
      diabetic foot and should ideally be referred to an appropriate multidisciplinary
      team.

PMID- 12180893
TI  - Recent advances in the treatment of AIDS-related Kaposi's sarcoma.
AB  - Kaposi's sarcoma (KS) is the most common malignancy associated with HIV infection
      and is considered an AIDS defining condition by the US Centers of Disease Control
      Guidelines. Several advances in the treatment of AIDS-related KS have been
      achieved over the past few years, even though a gold standard therapy for KS has
      not yet been defined and treatment must be tailored to individual needs. Since
      the availability of highly active antiretroviral therapy (HAART), a dramatic
      clinical response has been documented in patients with KS, making HAART an
      essential approach in the management of KS in most, if not all, patients with
      AIDS-related KS. However, in case of aggressive, visceral, and/or life
      threatening KS, more complex therapeutic schedules have to be taken into account,
      including chemotherapy, radiotherapy, and/or immunotherapy. In general, systemic
      treatment for KS is limited to widespread, symptomatic disease, whereas local
      interventions are indicated for minimal, cosmetically troublesome lesions. Among
      new cytotoxic agents, liposomal anthracyclines and paclitaxel are highly
      effective molecules for KS and have been approved by the US Food and Drug
      Administration (FDA) as first-line and second-line monotherapy, respectively, for
      advanced KS. Furthermore, a greater understanding of the pathogenesis of KS has
      lead to the development of an array of new experimental agents. Many
      antiangiogenic agents such as AGM 1470 (TNP 470), thalidomide, and glufanide
      disodium (IM 862) have produced encouraging responses in patients with KS and
      large clinical trials are in progress. Retinoic acids may also block
      neoangiogenesis as well as proliferation of KS cells in vitro, and they have been
      used either systemically or topically with a high response rate. Thus, a topical
      compound 0.1% alitretinoin gel was approved in 1999 by the FDA for the treatment
      of skin lesions associated with KS. Human chorionic gonadotropin, a hormonal
      agent, has shown a strong inhibitory activity in KS cells, but its role in the
      regression of KS lesions is not clear. Finally, the identification of a novel
      gamma-herpesvirus, human herpesvirus-8, as a causative agent for KS, together
      with novel antiangiogenic compounds, such as metalloproteinase inhibitors, may
      offer promising targets for the therapy of KS.

PMID- 12180895
TI  - Treatment of mucocutaneous presentations of herpes simplex virus infections.
AB  - Infections by herpes simplex virus (HSV) types I and II are diverse and quite
      frequent. After primary infection, the virus establishes a life-long latency in
      the sensory ganglia and recrudescences may occur at an unpredictable rate.
      Recurrent labial and genital herpes infections represent the majority of clinical
      manifestations of HSV infections. Their management is currently well established
      using evidence-based medicine data. Primary labial herpes is generally not
      treated with antivirals in otherwise healthy children, although intravenous
      aciclovir may be offered in severe primary infections, particularly in the
      immunocompromised patient. The decision whether or not to treat recurrent labial
      herpes should be evaluated individually and depends on the frequency and severity
      of relapses, the impairment of the quality of life, and the cost of therapy.
      Patients with mild disease may benefit from topical therapy, and those with
      severe and frequent recurrences may be considered for intermittent or long-term
      oral antiviral therapy. Primary genital herpes is treated with oral or
      intravenous antivirals, depending on the severity of the infection and associated
      symptoms. Recurrent genital herpes can be managed with episodic short courses of
      oral antivirals in patients whose recurrences are moderate to severe and rare,
      and have a clear prodrome. Patients with >5 episodes/year, severe recurrences or
      unrecognisable prodromes may be best managed with long-term suppressive antiviral
      prophylaxis. HSV is also responsible for a variety of other clinical
      manifestations, including herpetic whitlow, neonatal infection, disseminated and
      atypical cutaneous infections, traumatic herpes, eczema herpeticum, and HSV
      associated erythema multiforme. HSV infection may also represent a complication
      following cosmetic procedures of the oro-facial region, surgical and dental
      interventions, sun exposure and burns. Precise treatment guidelines for these HSV
      infections are not firmly established.

PMID- 12180896
TI  - The management of rosacea.
AB  - Rosacea is a multiphasic disease which is associated with flushing, erythrosis,
      papulopustular rosacea and phymas; each phase is likely to have its own
      treatment. Flushing is better prevented rather than treated, and its etiology
      investigated. Beta-blockers, atenolol in particular, are worthy of prophylactic
      trials examining their efficacy in treating the flushing associated with rosacea.
      Currently, clonidine is the only drug available for the treatment of flushing.
      Treatment for erythrosis includes topical and systemic therapies. Metronidazole
      1% cream and azelaic acid 20% cream have been reported to reduce the severity
      score of erythema. The systemic treatment of erythrosis is based on the
      association of Helicobacter pylori with rosacea. However, this role is still
      being debated. Eradication of H. pylori can be achieved using a triple therapy
      regimen lasting 1 to 2 weeks [omeprazole and a combination of two antibacterials
      (a choice from clarithromycin, metronidazole or amoxicillin)]. Both the flashlamp
      pumped long-pulse dye laser and the potassium-titanyl-phosphate laser may be used
      in the treatment of facial telangiectases. Both systemic and topical remedies may
      be used to treat the papulopustules of rosacea. Systemic treatment includes
      metronidazole, doxycycline, minocycline, clarithromycin and isotretinoin, while
      topical treatment is based on metronidazole cream and gel. The presence of
      Demodex folliculorum is important in the inflammatory reaction, whether it is
      pathogenetic or not. Crotamiton 10% cream or permethrin 5% cream may be useful
      medications for papulopustular rosacea, although they are rarely successful in
      eradicating D. folliculorum. Oral or topical ivermectin may also be useful in
      such cases. Ocular involvement is common in patients with cutaneous rosacea and
      can be treated with orally administered or topical antibacterials. Once
      rhinophyma starts to be evident, the only way to correct it is by aggressive
      dermatosurgical procedures. Decortication and various types of lasers can also be
      used. Associated conditions, such as seborrheic dermatitis and possible contact
      sensitizations, deserve attention.

PMID- 12180897
TI  - Dermatological complications of obesity.
AB  - Obesity is a health problem of considerable magnitude in the Western world.
      Dermatological changes have been reported in patients with obesity, including:
      acanthosis nigricans and skin tags (due to insulin resistance); hyperandrogenism;
      striae due to over extension; stasis pigmentation due to peripheral vascular
      disease; lymphedema; pathologies associated with augmented folds; morphologic
      changes in the foot anatomy due to excess load; and complications that may arise
      from hospitalization. Acanthosis nigricans plaques can be managed by improved
      control of hyperinsulinemia; the vitamin D3 analog calcipitriol has also been
      shown to be effective. Skin tags can be removed by snipping with curved scissors,
      by cryotherapy or by electrodesiccation. Hyperandrogenism, a result of increased
      production of endogenous androgens due to increased volumes of adipose tissue
      (which synthesizes testosterone) and hyperinsulinemia (which increases the
      production of ovarian androgens) needs to be carefully assessed to ensure
      disorders such as virilizing tumors and congenital adrenal hyperplasia are
      treated appropriately. Treatment of hyperandrogenism should be centred on
      controlling insulin levels; weight loss, oral contraceptive and antiandrogenic
      therapies are also possible treatment options. The etiology of striae distensae,
      also known as stretch marks, is yet to be defined and treatment options are
      unsatisfactory at present; striae rubra and alba have been treated with a pulsed
      dye laser with marginal success. The relationship between obesity and varicose
      veins is controversial; symptoms are best prevented by the use of elastic
      stockings. Itching and inflammation associated with stasis pigmentation, the
      result of red blood cells escaping into the tissues, can be treated with
      corticosteroids. Lymphedema is associated with dilatation of tissue channels,
      reduced tissue oxygenation and provides a culture medium for bacterial growth.
      Lymphedema treatment is directed towards reducing the limb girth and weight, and
      the prevention of infection. Intertrigo is caused by friction between skin
      surfaces, combined with moisture and warmth, resulting in infection. This
      infection, most commonly candidiasis, is best treated with topical antifungal
      agents; systemic antifungal therapy may be required in some patients. Excess load
      on the feet can result in morphological changes that require careful diagnosis;
      insoles may offer some symptom relief while control of obesity is achieved.
      Obesity-related dermatoses associated with hospitalization, such as pressure
      ulcers, diminished wound healing, dermatoses secondary to respiratory conditions,
      and incontinence, must all be carefully managed with an emphasis on prevention
      where possible. Recognition and control of the dermatological complications of
      obesity play an important role in diminishing the morbidity of obesity.

PMID- 12180900
TI  - Cutaneous drug reaction case reports: from the world literature.
AB  - Skin disorders are the most common adverse reactions attributed to drugs. Any
      skin disorder can be imitated, induced or aggravated by drugs. To help you keep
      up-to-date with the very latest skin reactions occurring with both new and
      established drugs, this section of the journal brings you information selected
      from the adverse drug reaction alerting service Reactions Weekly. The following
      case reports are selected from the very latest to be published in the world
      dermatology literature. Any claim of a first report has been verified by a search
      of AdisBase (a proprietary database of Adis International) and Medline. In
      addition, the World Health Organization (WHO) Adverse Drug Reactions database is
      also searched. This database, maintained by the Uppsala Monitoring Centre in
      Sweden, is the largest and most comprehensive adverse drug reaction source in the
      world, with information obtained from National Centers of 65 affiliate countries.
      Each case report is assessed for seriousness using the FDA MedWatch definition of
      serious (patient outcome is: death; life-threatening; hospitalization;
      disability; congenital anomaly; or requires intervention to prevent permanent
      impairment or damage).

PMID- 12180898
TI  - E-Z Derm a porcine heterograft material.

PMID- 12180901
TI  - Recent developments in oligosaccharide synthesis: tactics, solid-phase synthesis
      and library synthesis.
AB  - Oligosaccharides, commonly found on the cell surfaces, are deeply involved in a
      variety of important biological functions, yet demanding difficulties
      synthesizing such structures limit the investigation of their functions.
      Technologies to chemically synthesize these oligosaccharides have dramatically
      advanced during the last two decades mainly due to the introduction of good
      anomeric leaving groups. In addition, tactical analyses have been addressed to
      enhance the overall efficiency of oligosaccharide synthesis. Based on the
      advancement of solution-phase chemistry, solid-phase technologies are being
      investigated in connection with the current trend of combinatorial chemistry and
      high throughput screening. This review summarizes the necessary solution-phase
      methodologies, the status of solid-phase synthesis of oligosaccharides, and
      combinatorial synthesis of oligosaccharide libraries.

PMID- 12180902
TI  - Glycoconjugate libraries accessed by multicomponent reactions.
AB  - Glycobiology opens a wide field for new therapeutic approaches. However, the
      complexity and unavailability of various carbohydrate test compounds has excluded
      this class of natural products from modern screening systems. Alternatively,
      glycomimetics are considered to be more drug-like candidates for development. By
      means of multicomponent condensations (MCCs) utilizing suitable carbohydrate
      synthons, rapid and effective access to glycoconjugate libraries can be obtained.
      The flexibility of MCCs allows the assembly of diverse carbohydrate containing
      libraries. It may be assumed that MCCs containing carbohydrate moieties will play
      an important role in glycomimetic chemistry and biology.

PMID- 12180903
TI  - Sugar amino acid based scaffolds--novel peptidomimetics and their potential in
      combinatorial synthesis.
AB  - To meet the growing demands for the development of new molecular entities for
      discovering new drugs and materials, organic chemists have started looking for
      new concepts to supplement traditional approaches. In one such approach, the
      expertise gained over the years in the area of organic synthesis and the rational
      drug-design concepts are combined together to create "nature-like" and yet
      unnatural organic molecules that are expected to provide leads in discovering new
      molecules. Emulating the basic principles followed by nature to build its vast
      repertoire of biomolecules, organic chemists are developing many novel
      multifunctional building blocks. Sugar amino acids constitute an important class
      of such polyfunctional scaffolds where the carboxyl, amino and hydroxyl groups
      provide an excellent opportunity for organic chemists to create structural
      diversities akin to nature's molecular arsenal. Recent advances in the area of
      combinatorial chemistry give unprecedented technological support for rapid
      compilations of sugar amino acid-based libraries exploiting the diversities of
      carbohydrate molecules and well-developed solid-phase peptide synthesis methods.
      This review chronicles the development of sugar amino acids as a novel class of
      peptidomimetic building blocks and their applications in generating desired
      secondary structures in peptides as well as in creating mimics of natural
      biopolymers.

PMID- 12180904
TI  - Synthesis of a 56 component library of sugar beta-peptides.
AB  - Many biological processes of vital importance are triggered by the molecular
      recognition of small carbohydrate units by proteins and receptors thus leading to
      the belief that carbohydrates could act as candidates for the design of new
      drugs. We have developed a new useful synthetic approach, which can be applied in
      a combinatorial manner, giving access to 1,1-di-substituted pyrans projecting
      amide side chains in both the alpha- and beta-directions. Thus, treatment of the
      readily accessible hemiketal (1) with TFA followed by trimethylsilyl
      trifluoromethanesulfonate (TMSOTf) in the presence of a nitrile gives
      dihydrooxazinones (2) via a new type of modified intramolecular Ritter reaction.
      The dihydrooxazinones (2) can either be isolated or used directly in reactions
      with a broad variety of amines. Final deprotection furnishes the 1,1-di
      substituted sugar beta-peptides having the general structure (4).

PMID- 12180905
TI  - Frontal affinity chromatography for the screening of mixtures.
AB  - A protein stationary phase for frontal affinity chromatography was prepared,
      containing biotinylated beta-galactosidase immobilized to controlled pore glass
      beads via covalently bonded streptavidin. Single microaffinity columns of
      approximately 30 pmol of active beta-galactosidase were prepared from this
      material and characterized with a known ligand by frontal analysis. These columns
      were used to measure the specific interactions between the bound beta
      galactosidase and a library of modified beta-galactopyranosides using
      electrospray mass spectrometry as the means of detection. The library contained
      89 entries, each representing 4 diastereomers for a total of 356 library members.
      A single entry was analysed revealing differential activity among the 4 isomers.
      The library was grouped into 10 mixtures of 24-40 members each with each mixture
      infused under frontal chromatographic conditions. This deconvolution procedure
      led to the identification of 34 entries containing isomers with K(d) values
      better than 10 microM. A method based on a displacement principle was implemented
      as a rapid prescreen which served as the basis for a parallel column high
      throughput screening assay.

PMID- 12180906
TI  - Complex I-mediated reactive oxygen species generation: modulation by cytochrome c
      and NAD(P)+ oxidation-reduction state.
AB  - Several lines of evidence indicate that mitochondrial reactive oxygen species
      (ROS) generation is the major source of oxidative stress in the cell. It has been
      shown that ROS production accompanies cytochrome c release in different apoptotic
      paradigms, but the site(s) of ROS production remain obscure. In the current
      study, we demonstrate that loss of cytochrome c by mitochondria oxidizing NAD(+)
      linked substrates results in a dramatic increase of ROS production and
      respiratory inhibition. This increased ROS production can be mimicked by
      rotenone, a complex I inhibitor, as well as other chemical inhibitors of electron
      flow that act further downstream in the electron transport chain. The effects of
      cytochrome c depletion from mitoplasts on ROS production and respiration are
      reversible upon addition of exogenous cytochrome c. Thus in these models of
      mitochondrial injury, a primary site of ROS generation in both brain and heart
      mitochondria is proximal to the rotenone inhibitory site, rather than in complex
      III. ROS production at complex I is critically dependent upon a highly reduced
      state of the mitochondrial NAD(P)(+) pool and is achieved upon nearly complete
      inhibition of the respiratory chain. Redox clamp experiments using the
      acetoacetate/L-beta-hydroxybutyrate couple in the presence of a maximally
      inhibitory rotenone concentration suggest that the site is approx. 50 mV more
      electronegative than the NADH/NAD(+) couple. In the absence of inhibitors, this
      highly reduced state of mitochondria can be induced by reverse electron flow from
      succinate to NAD(+), accounting for profound ROS production in the presence of
      succinate. These results lead us to propose a model of thermodynamic control of
      mitochondrial ROS production which suggests that the ROS-generating site of
      complex I is the Fe-S centre N-1a.

PMID- 12180907
TI  - Matrilin-2 interacts with itself and with other extracellular matrix proteins.
AB  - Matrilin-2 is a component of extracellular filamentous networks. To study the
      interactions by which it can be integrated into such assemblies, full-length and
      truncated forms of matrilin-2 were recombinantly expressed in HEK-293 cells and
      purified from conditioned medium. The recombinant proteins, when used in
      interaction assays, showed affinity to matrilin-2 itself, but also to other
      collagenous and non-collagenous extracellular matrix proteins. The interaction
      between matrilin-2 and collagen I was studied in greater detail and could be
      shown to occur at distinct sites on the collagen I molecule and to have a K (D)
      of about 3 x 10(-8) M. Interactions with some non-collagenous protein ligands
      were even stronger, with matrilin-2 binding to fibrillin-2, fibronectin and
      laminin-1-nidogen-1 complexes, with K (D) values in the range of 10(-8)-10(-11)
      M. Co-localization of matrilin-2 with these ligands in the dermal-epidermal
      basement membrane, in the microfibrils extending from the basement membrane into
      the dermis, and in the dermal extracellular matrix, indicates a physiological
      relevance of the interactions in the assembly of supramolecular extracellular
      matrix structures.

PMID- 12180910
TI  - Structural mechanisms of multidrug recognition and regulation by bacterial
      multidrug transcription factors.
AB  - The increase in bacterial resistance to multiple drugs represents a serious and
      growing health risk. One component of multidrug resistance (MDR) is a group of
      multidrug transporters that are often regulated at the transcriptional level by
      repressors and/or activators. Some of these transcription factors are also
      multidrug-binding proteins, frequently recognizing the same array of drugs that
      are effluxed by the transporters that they regulate. How a single protein can
      recognize such chemically disparate compounds is an intriguing question from a
      structural standpoint and an important question in future drug development
      endeavours. Unlike the multidrug transporters, the cytosolic multidrug-binding
      regulatory proteins are more tractable systems for structural analyses. Here, we
      describe recent crystallographic studies on MarR, BmrR and QacR, three bacterial
      transcription regulators that are also multidrug-binding proteins. Although our
      understanding of multidrug binding and transcriptional regulation by MarR is in
      its initial stages, the structure of a BmrR-TPP+-DNA complex has revealed
      important insights into the novel transcription activation mechanism of the MerR
      family, and the structures of a QacR-DNA complex and QacR bound to six different
      drugs have revealed not only the mechanism of induction of this repressor but has
      afforded the first view of any MDR protein bound to multiple drugs.

PMID- 12180909
TI  - Membrane perturbations induced by the apoptotic Bax protein.
AB  - The apoptotic protein Bax, in oligomeric form, is effective in promoting both
      leakage and lipid mixing in liposomes composed of cardiolipin and
      phosphatidylethanolamine and/or phosphatidylcholine, upon the addition of
      calcium. In contrast, monomeric Bax is not active. At low concentrations at which
      caspase-8-cut Bid (tBid) alone has little effect on leakage, tBid augments the
      leakage caused by monomeric Bax. When solutions of oligomeric Bax are diluted to
      lower detergent concentrations than those required for Bax oligomerization, the
      protein is initially active in inducing liposomal leakage, indicating that the
      potency of the oligomeric form is not a consequence of being initially added to
      the liposomes in a high detergent concentration. However, in solutions of low
      detergent concentration, in the absence of liposomes, the oligomer gradually
      loses its lytic potency. This is accompanied by a loss of binding of bis-ANS
      (4,4'-dianilino-1,1'-binaphthyl-5,5'-disulphonic acid), indicating the loss of
      exposed hydrophobic sites, as well as a loss of the ability of the protein to
      translocate to membranes. Membrane translocation was measured by an energy
      transfer assay. It was demonstrated that membrane binding was greatly enhanced by
      oligomerization and by the presence of calcium. Thus the membrane-active form of
      Bax is unstable in the absence of detergent or lipid. In addition, we find that
      translocation to the membrane is enhanced by oligomerization as well as by the
      presence of high concentrations of calcium.

PMID- 12180912
TI  - Coiled-coil proteins associated with type III secretion systems: a versatile
      domain revisited.
AB  - The pathogenic potential of many Gram-negative bacteria is indicated by the
      possession of a specialized type III secretion system that is used to deliver
      virulence effector proteins directly into the cellular environment of the
      eukaryotic host. Extracellular assemblies of secreted proteins contrive a
      physical link between the pathogen and host cytosol and enable the translocated
      effectors to bypass the bacterial and host membranes in a single step. Subsequent
      interactions of some effector proteins with host cytoskeletal and signalling
      proteins result in modulation of the cytoskeletal architecture of the aggressed
      cell and facilitate entry, survival and dissemination of the pathogen. Although
      the secreted components of type III secretion systems are diverse, many are
      predicted to share a common coiled-coil structural feature. Coiled-coils are
      ubiquitous and highly versatile assembly motifs found in a wide range of
      structural and regulatory proteins. The prevalence of these domains in secreted
      virulence effector proteins suggests a fundamental contribution to multiple
      aspects of their function, and evidence accumulating from functional studies
      suggests an intrinsic involvement of coiled-coils in subunit assembly,
      translocation and flexible interactions with multiple bacterial and host
      proteins. The known functional flexibility that coiled-coil domains confer upon
      proteins provides insights into some of the pathogenic mechanisms used during
      interaction with the host.

PMID- 12180911
TI  - Mechanochemical ATPases and transcriptional activation.
AB  - Transcriptional activator proteins that act upon the sigma54-containing form of
      the bacterial RNA polymerase belong to the extensive AAA+ superfamily of ATPases,
      members of which are found in all three kingdoms of life and function in diverse
      cellular processes, often via chaperone-like activities. Formation and collapse
      of the transition state of ATP for hydrolysis appears to engender the interaction
      of the activator proteins with sigma54 and leads to the protein structural
      transitions needed for RNA polymerase to isomerize and engage with the DNA
      template strand. The common oligomeric structures of AAA+ proteins and the
      creation of the active site for ATP hydrolysis between protomers suggest that the
      critical changes in protomer structure required for productive interactions with
      sigma54-holoenzyme occur as a consequence of sensing the state of the gamma
      phosphate of ATP. Depending upon the form of nucleotide bound, different
      functional states of the activator are created that have distinct substrate and
      chaperone-like binding activities. In particular, interprotomer ATP interactions
      rely upon the use of an arginine finger, a situation reminiscent of GTPase
      activating proteins.

PMID- 12180908
TI  - Protein kinase A translocation and insulin secretion in pancreatic beta-cells:
      studies with adenylate cyclase toxin from Bordetella pertussis.
AB  - Activation of protein kinase A (cAMP-dependent protein kinase; PKA) triggers
      insulin secretion in the beta-cell. Adenylate cyclase toxin (ACT), a bacterial
      exotoxin with adenylate cyclase activity, and forskolin, an activator of
      adenylate cyclase, both dose-dependently increased insulin secretion in the
      presence, but not the absence, of glucose in insulin-secreting betaTC3 cells. The
      stimulation of cAMP release by either agent was dose-dependent but glucose
      independent. Omission of extracellular Ca(2+) totally abolished the effects of
      ACT on insulin secretion and cytosolic cAMP accumulation. ACT and forskolin
      caused rapid and dramatic increases in cytosolic Ca(2+), which were blocked by
      nifedipine and the omission of extracellular Ca(2+). Omission of glucose
      completely blocked the effects of forskolin and partially blocked the effects of
      ACT on cytosolic Ca(2+). PKA alpha, beta and gamma catalytic subunits (Calpha,
      Cbeta and Cgamma respectively) were identified in betaTC6 cells by confocal
      microscopy. Glucose and glucagon-like polypeptide-1 (GLP-1) caused translocation
      of Calpha to the nucleus and of Cbeta to the plasma membrane and the nucleus, but
      did not affect the distribution of Cgamma. In conclusion, glucose and GLP-1
      amplify insulin secretion via cAMP production and PKAbeta activation.

PMID- 12180914
TI  - Characterization of a fungal protein kinase from Cryphonectria parasitica and its
      transcriptional upregulation by hypovirus.
AB  - The chestnut blight fungus Cryphonectria parasitica and its hypovirus comprise
      useful model system to study the mechanisms of hypoviral infection. We used
      degenerate primers based on fungal protein kinases to isolate a gene, cppk1,
      which encodes a novel Ser/Thr protein kinase of C. parasitica. The gene showed
      highest homology to ptk1, a Ser/Thr protein kinase from Trichoderma reesei. The
      encoded protein had a predicted mass of 70.5 kDa and a pI of 7.45. Northern blot
      analyses revealed that the cppk1 transcript was expressed from the beginning of
      culture, with a slight increase by 5 days of culture. However, its expression was
      specifically affected by the presence of virus, and it was transcriptionally
      upregulated in the fungal strain infected with the hypovirus. A kinase assay
      using Escherichia coli-derived CpPK1 revealed CpPK1-specific phosphorylated
      proteins with estimated masses of 50 kDa and 44 kDa. In addition, the
      phosphorylation of both proteins was higher in a cell-free extract from the
      hypovirulent strain. The increased expression of cppk1 by the introduction of an
      additional copy results in a subset of viral symptoms of reduced pigmentation and
      conidiation in a virus-free isolate. cppk1 overexpression also causes the
      downregulation of mating factor genes Mf2/1 and Mf2/2, resulting in female
      sterility. The present study suggests that the hypovirus disturbs fungal
      signalling by transcriptional upregulation of cppk1, which results in reduced
      pigmentation and conidiation and female sterility.

PMID- 12180913
TI  - Overexpression of White Collar-1 (WC-1) activates circadian clock-associated
      genes, but is not sufficient to induce most light-regulated gene expression in
      Neurospora crassa.
AB  - Many processes in fungi are regulated by light, but the molecular mechanisms are
      not well understood. The White Collar-1 (WC-1) protein is required for all known
      blue-light responses in Neurospora crassa. In response to light, WC-1 levels
      increase, and the protein is transiently phosphorylated. To test the hypothesis
      that the increase in WC-1 levels after light treatment is sufficient to activate
      light-regulated gene expression, we used microarrays to identify genes that
      respond to light treatment. We then overexpressed WC-1 in dark-grown tissue and
      used the microarrays to identify genes regulated by an increase in WC-1 levels.
      We found that 3% of the genes were responsive to light, whereas 7% of the genes
      were responsive to WC-1 overexpression in the dark. However, only four out of 22
      light-induced genes were also induced by WC-1 overexpression, demonstrating that
      changes in the levels of WC-1 are not sufficient to activate all light-responsive
      genes. The WC proteins are also required for circadian rhythms in dark-grown
      cultures and for light entrainment of the circadian clock, and WC-1 protein
      levels show a circadian rhythm in the dark. We found that representative samples
      of the mRNAs induced by over-expression of WC-1 show circadian fluctuations in
      their levels. These data suggest that WC-1 can mediate both light and circadian
      responses, with an increase in WC-1 levels affecting circadian clock-responsive
      gene regulation and other features of WC-1, possibly its phosphorylation,
      affecting light-responsive gene regulation.

PMID- 12180915
TI  - Adaptation of protein secretion to extremely high-salt conditions by extensive
      use of the twin-arginine translocation pathway.
AB  - Halophilic archaea thrive in environments with salt concentrations approaching
      saturation. However, little is known about the way in which these organisms
      stabilize their secreted proteins in such 'hostile' conditions. Here, we present
      data suggesting that the utilization of protein translocation pathways for
      protein secretion by the Halobacteriaceae differs significantly from that of non
      haloarchaea, and most probably represents an adaptation to the high-salt
      environment. Although most proteins are secreted via the general secretion (Sec)
      machinery, the twin-arginine translocation (Tat) pathway is mainly used for the
      secretion of redox proteins and is distinct from the Sec pathway, in that it
      allows cytoplasmic folding of secreted proteins. tatfind (developed in this
      study) was used for systematic whole-genome analysis of Halobacterium sp. NRC-1
      and several other prokaryotes to identify putative Tat substrates. Our analyses
      revealed that the vast majority of haloarchaeal secreted proteins were predicted
      substrates of the Tat pathway. Strikingly, most of these putative Tat substrates
      were non-redox proteins, the homologues of which in non-haloarchaea were
      identified as putative Sec substrates. We confirmed experimentally that the
      secretion of one such putative Tat substrate depended on the twin-arginine motif
      in its signal sequence. This extensive utilization of the Tat pathway in
      haloarchaea suggests an evolutionary adaptation to high-salt conditions by
      allowing cytoplasmic folding of secreted proteins before their secretion.

PMID- 12180916
TI  - Characterization of Cah, a calcium-binding and heat-extractable autotransporter
      protein of enterohaemorrhagic Escherichia coli.
AB  - We have identified and characterized a protein of enterohaemorrhagic Escherichia
      coli (EHEC) serotype O157:H7 that shares homology with antigen 43 and AIDA-I of
      E. coli. The gene encoding this protein consists of a 2850 bp open reading frame
      and was named cah for calcium binding antigen 43 homologue. The prototype EHEC
      strain EDL933 possesses identical duplicate copies of cah (cah1 and cah2), which
      showed 100% identity at the nucleotide level. We showed that E. coli K-12
      containing the recombinant cah gene produced two proteins, an approximately 80
      kDa outer membrane protein and a 43.0 kDa heat-extractable protein. The Cah
      protein contains a predicted 52-amino-acid extended signal sequence found in
      several autotransporter proteins, and N-terminal sequencing data indicated that
      the 43.0 kDa passenger protein was derived from cleavage of the signal sequence
      from alanine at position 53. Phenotypes such as autoaggregation and change in
      bacterial shape were observed when a recombinant plasmid containing the cah gene
      was introduced into a laboratory E. coli strain, and these phenotypes were
      eliminated upon mutation of the cah gene. The passenger domain contains six
      domains found in calcium-binding proteins, and the recombinant Cah passenger
      protein bound 45Ca2+. In E. coli O157:H7, Cah is a heat-extractable protein, the
      expression of which is induced in minimal essential media and under divalent ion
      depleting conditions; it also participates in the formation of biofilms. Our
      results provide insight into the expression, secretion and preliminary features
      of the calcium-binding Cah autotransporter protein of EHEC O157:H7.

PMID- 12180917
TI  - Molecular dissection of Salmonella FliH, a regulator of the ATPase FliI and the
      type III flagellar protein export pathway.
AB  - FliH is a soluble component of the flagellar export apparatus that binds to the
      ATPase FliI, and negatively regulates its activity. The 235-amino-acid FliH
      dimerizes and interacts with FliI to form a hetero-trimeric (FliH)2FliI complex.
      In the present work, the importance of different regions of FliH was examined. A
      set of 24 scanning deletions of 10 amino acids was constructed over the entire
      FliH sequence, along with several combined deletions of 40 amino acids and
      truncations of both N- and C-termini. The mutant proteins were examined with
      respect to (i) complementation; (ii) dominance and multicopy effects; (iii)
      interaction with wild-type FliH; (iv) interaction with FliI; (v) inhibition of
      the ATPase activity of FliI; and (vi) interaction with the putative general
      chaperone FliJ. Analysis of the deletion mutants revealed a clear functional
      demarcation between the FliH N- and C-terminal regions. The 10-amino-acid
      deletions throughout most of the N-terminal half of the sequence complemented and
      were not dominant, whereas those throughout most of the C-terminal half did not
      complement and were dominant. FliI binding was disrupted by C-terminal deletions
      from residue 101 onwards, indicating that the C-terminal domain of FliH is
      essential for interaction with FliI. FliH dimerization was abolished by deletion
      of residues 101-140 in the centre of the sequence, as were complementation,
      dominance and interaction with FliI and FliJ. The importance of this region was
      confirmed by the fact that fragment FliHC2 (residues 99-235) interacted with FliH
      and FliI, whereas fragment FliHC1 (residues 119-235) did not. FliHC2 formed a
      relatively unstable complex with FliI and showed biphasic regulation of ATPase
      activity, suggesting that the FliH N-terminus stabilizes the (FliH)2FliI complex.
      Several of the N-terminal deletions tested permitted close to normal ATPase
      activity of FliI. Deletion of the last five residues of FliH caused a fivefold
      activation of ATPase activity, suggesting that this region of FliH governs a
      switch between repression and activation of FliI. Deletion of the first 10
      residues of FliH abolished complementation, severely reduced its interaction with
      FliJ and uncoupled its role as a FliI repressor from its other export functions.
      Based on these data, a model is presented for the domain construction and
      function of FliH in complex with FliI and FliJ.

PMID- 12180918
TI  - Donor strand complementation mechanism in the biogenesis of non-pilus systems.
AB  - The F1 antigen of Yersinia pestis belongs to a class of non-pilus adhesins
      assembled via a classical chaperone-usher pathway. Such pathways consist of PapD
      like chaperones that bind subunits and pilot them to the outer membrane usher,
      where they are assembled into surface structures. In a recombinant Escherichia
      coli model system, chaperone-subunit (Caf1M:Caf1n) complexes accumulate in the
      periplasm. Three independent methods showed that these complexes are rod- or coil
      shaped linear arrays of Caf1 subunits capped at one end by a single copy of Caf1M
      chaperone. Deletion and point mutagenesis identified an N-terminal donor strand
      region of Caf1 that was essential for polymerization in vitro, in the periplasm
      and at the cell surface, but not for chaperone-subunit interaction. Partial
      protease digestion of periplasmic complexes revealed that this region becomes
      buried upon formation of Caf1:Caf1 contacts. These results show that, despite the
      capsule-like appearance of F1 antigen, the basic structure is assembled as a
      linear array of subunits held together by intersubunit donor strand
      complementation. This example shows that strikingly different architectures can
      be achieved by the same general principle of donor strand complementation and
      suggests that a similar basic polymer organization will be shared by all surface
      structures assembled by classical chaperone-usher pathways.

PMID- 12180919
TI  - A peroxide-induced zinc uptake system plays an important role in protection
      against oxidative stress in Bacillus subtilis.
AB  - In Bacillus subtilis, hydrogen peroxide (H2O2) induces expression of the PerR
      regulon including catalase (KatA), alkyl hydroperoxide reductase and the DNA
      binding protein MrgA. We have identified the P-type metal-transporting ATPase
      ZosA (formerly YkvW) as an additional member of the perR regulon. Expression of
      zosA is induced by H2O2 and repressed by the PerR metalloregulatory protein,
      which binds to two Per boxes in the promoter region. Physiological studies
      implicate ZosA in Zn(II) uptake. ZosA functions together with two Zur-regulated
      uptake systems and one known efflux system to maintain Zn(II) homeostasis. ZosA
      is the major pathway for zinc uptake in cells growing with micromolar levels of
      Zn(II) that are known to repress the two Zur-regulated transporters. A perR
      mutant is sensitive to high levels of zinc, and this sensitivity is partially
      suppressed by a zosA mutation. ZosA is important for resistance to both H2O2 and
      the thiol-oxidizing agent diamide. This suggests that increased intracellular
      Zn(II) may protect thiols from oxidation. In contrast, catalase is critical for
      H2O2 resistance but does not contribute significantly to diamide resistance.
      Growth of cells with elevated zinc significantly increases resistance to high
      concentrations of H2O2, and this effect requires ZosA. Our results indicate that
      peroxide stress leads to the upregulation of a dedicated Zn(II) uptake system
      that plays an important role in H2O2 and disulphide stress resistance.

PMID- 12180920
TI  - Molecular and functional characterization of kshA and kshB, encoding two
      components of 3-ketosteroid 9alpha-hydroxylase, a class IA monooxygenase, in
      Rhodococcus erythropolis strain SQ1.
AB  - 9 alpha-Hydroxylation of 4-androstene-3,17-dione (AD) and 1,4-androstadiene-3,17
      dione (ADD) is catalysed by 3-ketosteroid 9 alpha-hydroxylase (KSH), a key enzyme
      in microbial steroid catabolism. Very limited knowledge is presently available on
      the KSH enzyme. Here, we report for the first time the identification and
      molecular characterization of genes encoding KSH activity. The kshA and kshB
      genes, encoding KSH in Rhodococcus erythropolis strain SQ1, were cloned by
      functional complementation of mutant strains blocked in AD(D) 9 alpha
      hydroxylation. Analysis of the deduced amino acid sequences of kshA and kshB
      showed that they contain domains typically conserved in class IA terminal
      oxygenases and class IA oxygenase reductases respectively. By definition, class
      IA oxygenases are made up of two components, thus classifying the KSH enzyme
      system in R. erythropolis strain SQ1 as a two-component class IA monooxygenase
      composed of KshA and KshB. Unmarked in frame gene deletion mutants of parent
      strain R. erythropolis SQ1, designated strains RG2 (kshA mutant) and RG4 (kshB
      mutant), were unable to grow on steroid substrates AD(D), whereas growth on 9
      alpha-hydroxy-4-androstene-3,17-dione (9OHAD) was not affected. Incubation of
      these mutant strains with AD resulted in the accumulation of ADD (30-50%
      conversion), confirming the involvement of KshA and KshB in AD(D) 9 alpha
      hydroxylation. Strain RG4 was also impaired in sterol degradation, suggesting a
      dual role for KshB in both sterol and steroid degradation.

PMID- 12180921
TI  - Conflicting needs for a Salmonella hypervirulence gene in host and non-host
      environments.
AB  - The Gram-negative pathogen Salmonella enterica harbours a periplasmic D-Ala-D-Ala
      dipeptidase (termed PcgL), which confers the ability to grow on D-Ala-D-Ala as
      sole carbon source. We now demonstrate that inactivation of the pcgL gene renders
      Salmonella hypervirulent. This phenotype results from the accumulation of
      peptidoglycan-derived D-Ala-D-Ala in the pcgL mutant and not from an
      intrinsically faster growth rate. Synthetic D-Ala-D-Ala (but not L-Ala-L-Ala or D
      Ala) increased the number of wild-type Salmonella in the liver and spleen of mice
      within 24 h of injection, suggesting that D-Ala-D-Ala interferes with some aspect
      of innate immunity. However, the pcgL mutant was unable to grow on D-Ala-D-Ala as
      sole carbon source and was defective for survival in nutrient-poor conditions. We
      identified clinical isolates lacking D-Ala-D-Ala dipeptidase activity and unable
      to grow on D-Ala-D-Ala because of inactivation of the pcgL gene. Our data suggest
      that genes (such as pcgL) that, when mutated make pathogens more virulent, may be
      retained because their contribution to pathogen fitness in non-host environments
      outweighs potential advantages of the hypervirulent vari-ant in the infected
      host.

PMID- 12180922
TI  - Proteomic analysis of the Caulobacter crescentus stalk indicates competence for
      nutrient uptake.
AB  - Caulobacter crescentus, a Gram-negative alpha-purple proteobacterium, is an
      oligotroph that lives in aquatic environments dilute in nutrients. This bacterium
      divides asymmetrically. Part of this asymmetric cell division involves the
      formation of a prosthecum at one pole, referred to as the stalk, which replaces
      the flagellum of the motile swarmer cell. Little is known about the synthesis or
      function of the stalk. The stalk is an extension of the cell membranes and
      peptidoglycan layer, and stalk elongation is stimulated by phosphate starvation.
      In this study, we have taken advantage of two-dimensional gel (2D gel) electro
      phoresis as well as the fully sequenced genome of Caulobacter to study the
      proteome of the stalk. We modified a stalk-shedding mutant strain of Caulobacter
      crescentus to increase the yield of stalk material shed and performed 2D gel
      electrophoresis of purified stalks and cellular fractions. Comparison of the
      stalk 2D gel with the 2D gels of cell membrane and soluble fractions showed that
      the stalk is mostly free of cytoplasmic proteins and has a profile very similar
      to that of the cell membrane. Of the 172 proteins on a stalk 2D gel, we report
      the identification of 64 spots, corresponding to 39 different proteins present in
      the stalk of Caulobacter. The identifications include several TonB-dependent
      receptors, two OmpA family proteins, a dipeptidase, GlpQ, two alkaline
      phosphatases, 3-phytase, a putative TolC protein and 11 proteins of unknown
      function. These identifications are consistent with the hypothesis that the stalk
      plays a role in nutrient uptake.

PMID- 12180924
TI  - Stage-specific gene expression during sexual development in Phytophthora
      infestans.
AB  - Eight genes that are upregulated during sexual development in the heterothallic
      oomycete, Phytophthora infestans, were identified by suppression subtractive
      hybridization. Two genes showed very low but detectable expression in vegetative
      hyphae and became induced about 40- to >100-fold early in mating, before
      gametangial initials appeared. The remaining six loci were not induced until
      later in mating, coincident with the formation of gametangia and oospores, with
      induction levels ranging from 60- to >100-fold. Five genes were single copy, and
      three were members of families. Sequence analysis revealed that the predicted
      products of three of the genes had similarity to proteins that influence RNA
      stability, namely a ribonuclease activator, the pumilio family of RNA-binding
      proteins and RNase H. The products of two other mating-induced genes resembled
      two types of Phytophthora proteins previously shown to elicit plant defence
      responses. Each mating-induced gene was also expressed in a self-fertile strain,
      which was shown to be a heterokaryon. However, quantitative and qualitative
      differences existed in their expression in normal matings and in the self-fertile
      heterokaryon. Besides the mating-induced genes, two extrachromosomal RNA elements
      were identified.

PMID- 12180923
TI  - Identification of a second Listeria secA gene associated with protein secretion
      and the rough phenotype.
AB  - We describe the identification and characterization of a second secA gene in
      Listeria monocytogenes. This gene, termed secA2, is involved in smooth-rough
      phenotypic variation and secA2 expression contributes to bacterial virulence.
      Spontaneous rough (R-) variants of L. monocytogenes grow in chains and form rough
      colonies on solid media. A subset of R-variants, classified here as type I, also
      shows reduced secretion of an autolysin, p60. We find that disruptions and in
      frame deletions in secA2 confer phenotypes identical to those of spontaneous type
      I R-variants. Additionally, the secA2 genes from two spontaneous type I R
      variants encoded truncated SecA2 proteins. Mutations were not found in the secA2
      genes from the remaining five independent R-variants, four of which showed a
      distinct (type II) rough morphology and secreted wild-type levels of p60.
      Expression of an epitope-tagged SecA2 in the DeltasecA2 strain and a spontaneous
      R-variant restored normal cell septation and smooth colony morphology. These data
      suggest that mutations in both secA2 and other genes contribute to smooth-rough
      phase variation in L. monocytogenes. Expression of the full-length SecA2 also
      promotes secretion of p60 and a set of additional L. monocytogenes proteins. We
      hypothesize that SecA2-dependent protein secretion plays a role in the
      colonization of environmental and host surfaces.

PMID- 12180925
TI  - Modulation of bft expression by the Bacteroides fragilis pathogenicity island and
      its flanking region.
AB  - To establish a recombinant system for high-level expression of biologically
      active Bacteroides fragilis toxin (BFT), we studied the expression of bft in non
      toxigenic B. fragilis (NTBF) strains. The bft gene and the B. fragilis
      pathogenicity island (BfPAI) were cloned into NTBF strains with two distinct
      genetic patterns: (i) pattern II, strains lacking the BfPAI and its flanking
      region; and (ii) pattern III, strains lacking the BfPAI but containing its
      flanking region. Analysis of BFT activity of these recombinant strains on HT29/C1
      cells showed that both the BfPAI and its flanking regions are important to
      optimal BFT activity. Reverse transcription polymerase chain reaction (RT-PCR)
      analysis indicated that the BfPAI and its flanking regions modulate bft
      expression. Further experiments demonstrated that the approximately 700 bp region
      upstream of bft is the BfPAI region critical for optimal bft expression. We
      conclude that both the region flanking the BfPAI and approximately 700 bp region
      upstream of bft are crucial to maximal BFT production by ETBF strains.

PMID- 12180926
TI  - Type 1 fimbriae and extracellular polysaccharides are preeminent uropathogenic
      Escherichia coli virulence determinants in the murine urinary tract.
AB  - Escherichia coli is the leading cause of urinary tract infections (UTIs). Despite
      the association of numerous bacterial factors with uropathogenic E. coli (UPEC),
      few such factors have been proved to be required for UTI in animal models.
      Previous investigations of urovirulence factors have relied on prior
      identification of phenotypic characteristics. We used signature-tagged
      mutagenesis (STM) in an unbiased effort to identify genes that are essential for
      UPEC survival within the murine urinary tract. A library of 2049 transposon
      mutants of the prototypic UPEC strain CFT073 was constructed using mini-Tn5km2
      carrying 92 unique tags and screened in a murine model of ascending UTI. After
      initial screening followed by confirmation in co-infection experiments, 19
      survival-defective mutants were identified. These mutants were recovered in
      numbers 101- to 106-fold less than the wild type in the bladder, kidneys or urine
      or at more than one site. The transposon junctions from each attenuated mutant
      were sequenced and analysed. Mutations were found in: (i) the type 1 fimbrial
      operon; (ii) genes involved in the biosyn-thesis of extracellular polysaccharides
      including group I capsule, group II capsule and enterobacterial common antigen;
      (iii) genes involved in metabolic pathways; and (iv) genes with unknown function.
      Five of the genes identified are absent from the genome of the E. coli K-12
      strain. Mutations in type 1 fimbrial genes resulted in severely attenuated
      colonization, even in the case of a mutant with an insertion upstream of the fim
      operon that affected the rate of fimbrial switching from the 'off' to the 'on'
      phase. Three mutants had insertions in a new type II capsule biosynthesis locus
      on a pathogenicity island and were impaired in the production of capsule in vivo.
      An additional mutant with an insertion in wecE was unable to synthesize
      enterobacterial common antigen. These results confirm the pre-eminence of type 1
      fimbriae, establish the importance of extracellular polysaccharides in the
      pathogenesis of UTI and identify new urovirulence determinants.

PMID- 12180927
TI  - Listeria monocytogenes bile salt hydrolase is a PrfA-regulated virulence factor
      involved in the intestinal and hepatic phases of listeriosis.
AB  - Listeria monocytogenes is a bacterial pathogen causing severe food-borne
      infections in humans and animals. It can sense and adapt to a variety of harsh
      microenvironments outside as well as inside the host. Once ingested by a
      mammalian host, the bacterial pathogen reaches the intestinal lumen, where it
      encounters bile salts which, in addition to their role in digestion, have
      antimicrobial activity. Comparison of the L. monocytogenes and Listeria innocua
      genomes has revealed the presence of an L. monocytogenes-specific putative gene
      encoding a bile salt hydrolase (BSH). Here, we show that the bsh gene encodes a
      functional intracellular enzyme in all pathogenic Listeria species. The bsh gene
      is positively regulated by PrfA, the transcriptional activator of known L.
      monocytogenes virulence genes. Moreover, BSH activity increases at low oxygen
      concentration. Deletion of bsh results in decreased resistance to bile in vitro,
      reduced bacterial faecal carriage after oral infection of the guinea-pigs,
      reduced virulence and liver colonization after intravenous inoculation of mice.
      Taken together, these results demonstrate that BSH is a novel PrfA-regulated L.
      monocytogenes virulence factor involved in the intestinal and hepatic phases of
      listeriosis.

PMID- 12180928
TI  - A Rho-dependent phase-variable transcription terminator controls expression of
      the FimE recombinase in Escherichia coli.
AB  - The fim switch is a 314 bp segment of invertible chromosomal DNA that is
      responsible for phase-variable expression of type 1 fimbriae in Escherichia coli.
      The switch harbours the promoter of the fimA gene. This codes for the type 1
      fimbrial subunit protein and, when the promoter is directed towards fimA (phase
      ON), the bacteria are fimbriate and, when it is directed away, the cells are
      afimbriate. The switch lies immediately downstream from the fimE gene, coding for
      a tyrosine site-specific recombinase that catalyses inversion of the switch from
      the ON to the OFF phase. It has been suggested previously that, because the fim
      switch lies immediately downstream from the fimE gene, expression of FimE could
      be subject to control by antisense RNA in phase OFF bacteria in which the
      promoter harboured within the fim switch is oriented against the direction of
      transcription of the fimE gene. In this study, no effect of inducible fimE
      antisense RNA, expressed in cis or in trans, on FimE expression was detected. In
      phase ON cells, fimE mRNA extends across the switch into fimA, whereas in phase
      OFF cells, it terminates within the switch. This termination is Rho dependent and
      is abolished in a rho mutant. The extended fimE found in phase ON cells is more
      stable and results in an approximately fivefold increase in FimE protein compared
      with phase OFF bacteria. In the absence of Rho factor, fimE mRNA is equally
      stable in phase ON and phase OFF cells, and the levels of FimE recombinase are
      also equal.

PMID- 12180929
TI  - The cell differentiation protein SpoIIE contains a regulatory site that controls
      its phosphatase activity in response to asymmetric septation.
AB  - Starvation induces Bacillus subtilis to initiate a -simple, two-cell
      developmental process that begins with an asymmetric cell division. Activation of
      the first compartment-specific transcription factor, sigmaF, is coupled to this
      morphological event. SpoIIE, a bifunctional protein, is essential for the
      compartment-specific activation of sigmaF and also has a morphogenic activity
      required for asymmetric cell division. SpoIIE consists of three domains: a
      hydrophobic N-terminal domain, which targets the protein to the membrane; a
      central domain, involved in oligomerization of SpoIIE and interaction with the
      cell division protein FtsZ; and a C-terminal domain comprising a PP2C protein
      phosphatase. Here, we report the isolation of mutations at the very beginning of
      the central domain of spoIIE, which are capable of activating sigmaF inde
      pendently of septum formation. Purified mutant proteins showed the same
      phosphatase activity as the wild-type protein in vitro. The mutant proteins were
      fully functional in respect of their localization to sites of asymmetric
      septation and support of asymmetric division. The data provide strong evidence
      that the phosphatase domain of SpoIIE is tightly regulated in a way that makes it
      respond to the formation of the asymmetric septum.

PMID- 12180930
TI  - Effect of var gene disruption on switching in Plasmodium falciparum.
AB  - The molecular mechanisms underpinning switching of variant antigens on the
      surface of Plasmodium falciparum-infected erythrocytes are poorly understood. We
      tested the hypothesis that insertional disruption of the A4var gene, one of two
      var genes located within the subtelomeric region of one end of chromosome 13,
      would result in a preferential switch in transcription to the adjacent R29var
      gene upon rosette selection. In this way, we aimed to mimic the preferential
      transcription of R29var in rosetting R29 parasites, a parasite line in which the
      A4var gene is deleted through a chromosome end truncation. Initial analysis of
      the knock-out parasite lines shows that the insertional disruption of the A4var
      gene prevents A4 PfEMP1 expression, but that switching transcription to other var
      gene variants is unaffected. Furthermore, analysis of var transcription in the
      knock-out parasite line during rosette selection shows that, rather than
      facilitating a switch to R29var gene transcription, this event was suppressed in
      the transfectants. These data, and the implications for epigenetic
      transcriptional control of var genes, are discussed.

PMID- 12180931
TI  - Dynamic response of catabolic pathways to autoacidification in Lactococcus
      lactis: transcript profiling and stability in relation to metabolic and energetic
      constraints.
AB  - The dynamic response of the central metabolic pathways to autoacidification
      (accumulation of organic acid fermentation products) in Lactococcus lactis was
      investigated in a global manner by integrating molecular data (cellular
      transcript concentrations, mRNA turnover) within physiological investigations of
      metabolic and energetic parameters. The decrease in pH associated with the
      accumulation of organic acids modified the physiological state of the cell
      considerably. Cytoplasmic acidification led to inhibition of enzyme activities
      and, consequently, to a diminished catabolic flux through glycolysis and a
      decreased rate of biochemical energy synthesis. This decrease in energy
      production together with the increased energy expenditure to counter cytoplasmic
      acidification led to energetic limitations for biomass synthesis. In these
      conditions, the specific growth rate decreased progressively, and growth
      ultimately stopped, although a diminished catabolic flux was maintained in the
      absence of growth. The cellular response to this phenomenon was to maintain
      significant levels of mRNA of catabolic genes, involving both continued
      transcription of the genes and also, in certain cases, an increase in transcript
      stability. Thus, translation was maintained, and intracellular concentration of
      certain enzymes increased, partially compensating for the inhibition of activity
      provoked by the diminished pH. When catabolic activity ceased after prolonged
      exposure to stress-induced stationary phase, endogenous RNA catabolism was
      observed.

PMID- 12180932
TI  - SakA MAP kinase is involved in stress signal transduction, sexual development and
      spore viability in Aspergillus nidulans.
AB  - In eukaryotic cells, environmental stress signals are transmitted by
      evolutionarily conserved MAPKs, such as Hog1 in the budding yeast Saccharomyces
      cerevisiae, Spc1 in the fission yeast Schizosaccharomyces pombe and p38/JNK in
      mammalian cells. Here, we report the identification of the Aspergillus nidulans
      sakA gene, which encodes a member of the stress MAPK family. The sakA gene is
      able to complement the S. pombe spc1- defects in both osmo-regulation and cell
      cycle progression. Moreover, SakA MAPK is activated in response to osmotic and
      oxidative stress in both S. pombe and A. nidulans. However, in contrast to hog1
      and spc1 mutants, the sakA null mutant is not sensitive to high osmolarity
      stress, indicating a different regulation of the osmostress response in this
      fungus. On the other hand, the DeltasakA mutant shows development and cell
      specific phenotypes. First, it displays premature steA-dependent sexual
      development. Second, DeltasakA mutant produces asexual spores that are highly
      sensitive to oxidative and heat shock stress and lose viability upon storage.
      Indeed, SakA is transiently activated early after induction of conidiation. Our
      results indicate that SakA MAPK is involved in stress signal transduction and
      repression of sexual development, and is required for spore stress resistance and
      survival.

PMID- 12180933
TI  - The Yersinia pseudotuberculosis Yut protein, a new type of urea transporter
      homologous to eukaryotic channels and functionally interchangeable in vitro with
      the Helicobacter pylori UreI protein.
AB  - Urea uptake in eukaryotes and prokaryotes occurs via diffusion or active
      transport across the cell membrane. Facilitated diffusion of urea in both types
      of organisms requires a single-component channel. In bacteria, these transport
      systems allow rapid access of urease to its substrate, resulting in ammonia
      production, which is needed either for resistance to acidity or as a nitrogen
      source. In Yersinia pseudotuberculosis, a ureolytic enteropathogenic bacterium, a
      gene of unknown function (yut) located near the urease locus was found to encode
      a putative membrane protein with weak homology to single-component eukaryotic
      urea transporters. When expressed in Xenopus oocytes, Yut greatly increases
      cellular permeability to urea. Inactivation of yut in Y. pseudotuberculosis
      results in diminished apparent urease activity and reduced resistance to acidity
      in vitro when urea is present in the medium. In the mouse model, bacterial
      colonization of the intestine mucosa is delayed with the Yut-deficient mutant.
      Although structurally unrelated, Yut and the Helicobacter pylori UreI urea
      channel were shown to be functionally interchangeable in vitro and are sufficient
      to allow urea uptake in both bacteria, thereby confirming their function in the
      respective parent organisms. Homologues of Yut were found in other yersiniae,
      Actinobacillus pleuropneumoniae, Brucella melitensis, Pseudomonas aeruginosa and
      Staphylococcus aureus. The Y. pseudotuberculosis Yut protein is therefore the
      first member of a novel class of bacterial urea permeases related to eukaryotic
      transporters.

PMID- 12180935
TI  - Agar gel immunodiffusion test (AGID) evaluation for detection of bovine
      paratuberculosis in Rio de Janeiro, Brazil.
AB  - AIMS: The aim of this study is to evaluate the AGID serological test for
      detection of antibodies anti-Mycobacterium paratuberculosis and its possible
      adoption as diagnostic method in our field conditions. METHODS: Bovine serum
      samples from dairy herds in Rio de Janeiro State, Brazil, were screened for the
      presence of antibodies against Myco. paratuberculosis using three different ELISA
      tests. A panel of 48 randomly selected sera were evaluated by an Agarose Gel
      Immunodiffusion (AGID) test using Protoplasmatic Paratuberculosis Antigen (PPA).
      AGID results were compared to the standards--the results of the three ELISA
      tests, and the specificity and sensitivity were calculated. RESULTS: From 48 sera
      tested for AGID, 14 (29.17%) were positive and 34 (70.83%) were negative. AGID
      sensitivity was 57% with two false-positive reactions, and specificity was 92.5%
      with nine false-negative results. The positive predictive value was calculated in
      85.7% for a confidence interval of 95%. SIGNIFICANCE AND IMPACT OF THE STUDY: Due
      to its low sensitivity and specificity rates, AGID test has shown to be
      unsatisfactory as a screening diagnostic method for subclinical herd infection,
      but it can be useful as a confirmatory test for clinical suspect animals.

PMID- 12180936
TI  - Susceptibility of Escherichia coli O157 and non-O157 isolates to lactate.
AB  - AIMS: To examine the effect of temperature on the antimicrobial efficacy of
      lactate and propionate against O157 and non-O157 Escherichia coli isolates.
      METHODS AND RESULTS: Lactate and, to a lesser extent, propionate effectively
      reduced viability at 37 degrees C. Ethanol enhanced this effect. Reducing the
      temperature to 20 or 5 degrees C caused an increase in survival in the presence
      of these organic acids with or without ethanol. At 20 degrees C the deltapH,
      membrane potential and intracellular lactate anion concentration were less than
      at 37 degrees C. CONCLUSIONS: The efficacy of lactate and propionate against E.
      coli O157 and non-O157 isolates is reduced at lower temperatures, perhaps due to
      the reduction in the deltapH, membrane potential and intracellular lactate anion
      concentration. SIGNIFICANCE AND IMPACT OF THE STUDY: These findings suggest that
      the usefulness of organic acids as decontaminants for E. coli O157 is temperature
      dependent.

PMID- 12180937
TI  - Helichrysum italicum extract interferes with the production of enterotoxins by
      Staphylococcus aureus.
AB  - AIMS: The purpose of this work was to evaluate the effect of Helichrysum italicum
      extract on enterotoxin (A-D) production by Staphylococcus aureus strains. METHODS
      AND RESULTS: The production of enterotoxins A-D in the presence or absence of
      H.italicum diethyl ether extract was estimated in microtiter plates using a
      reversed passive latex agglutination (SET-RPLA) kit (Oxoid, Basingstoke, UK). The
      results indicate that, in culture medium, inhibition of staphylococcal growth and
      enterotoxins appeared with 250-125 microg ml(-1) of the extract. Lower
      concentrations of the extract (62.5-31.25 microg ml(-1)) did not affect the final
      viable count of Staph. aureus but reduced the production of enterotoxins B and C.
      CONCLUSIONS: H. italicum interferes with growth and production of enterotoxins by
      Staph. aureus. SIGNIFICANCE AND IMPACT OF THE STUDY: There is considerable
      interest in the use of natural compounds as alternative methods to control
      undesirable pathogenic micro-organisms.

PMID- 12180938
TI  - flaA-like sequences containing internal termination codons (TAG) in urease
      positive thermophilic Campylobacter isolated in Japan.
AB  - AIMS: To demonstrate two flaA-like sequences containing two internal termination
      codons (TAG) in two Japanese strains of urease-positive thermophilic
      Campylobacter (UPTC). METHODS AND RESULTS: A primer pair of A1 and A2, which
      ought to generate a product of approx. 1700 bp of the flaA gene for Campylobacter
      jejuni, was used to amplify products of approx. 1450 bp for two Japanese strains
      of UPTC, CF89-12 and CF89-14. After molecular cloning and sequencing, the
      nucleotide sequences of the amplicons from the two strains were found to be 1461
      bp in length and to have nucleotide sequence differences in relation to each
      other at four nucleotide positions, respectively. CONCLUSIONS: Nucleotide and
      amino acid sequence alignment and homology analysis demonstrated that the
      polymerase chain reaction (PCR) amplicons from the two Japanese strains have
      approx. 83% nucleotide and 80% amino acid sequence homology to the possible open
      reading frame of the flaA gene of UPTC NCTC 12892. SIGNIFICANCE AND IMPACT OF THE
      STUDY: Surprisingly, both PCR amplicons from the Japanese UPTC have two internal
      termination codons (TAG) at nucleotide positions from 775 to 777 and 817 to 819,
      respectively.

PMID- 12180939
TI  - Influence of co-substrates on structure of microbial aggregates in long-chain
      fatty acid-fed anaerobic digesters.
AB  - AIMS: The purpose of this study was to investigate the influence of co
      substrates, such as glucose and cysteine, on the structure of microbial
      aggregates in anaerobic digesters treating oleate, a long-chain fatty acid
      (LCFA). METHODS AND RESULTS: Transmission electron microscopy (TEM) and confocal
      laser scanning microscopy (CLSM) were used to examine the structure of microbial
      aggregates. Fluorescence in situ hybridization (FISH) techniques were also used
      to characterize and localize the different trophic groups present in the
      aggregates. Oleate was found to inhibit the methanogenic activity and formation
      of granular biomass in digesters. The addition of co-substrates, such as glucose
      and cysteine either singly or in combination, increased the methanogenic activity
      and formation of granular biomass. Glucose was more effective than cysteine in
      reducing the inhibition by oleate on the methanogenic bacteria and in enhancing
      the formation of granules. CONCLUSIONS: The addition of nutrient substrate, such
      as glucose and cysteine could decrease the toxicity of LCFA on anaerobic
      granulation. SIGNIFICANCE AND IMPACT OF THE STUDY: The results suggest that the
      addition of other substrates might decrease the toxicity of LCFA on the
      granulation of biomass in anaerobic digesters and enhance methanogenic activity.
      A combination of TEM, CLSM and FISH techniques provides a better tool for
      visualizing microbial aggregates and for differentiating and localizing different
      microbial groups within these aggregates.

PMID- 12180940
TI  - Production of red pigment by submerged culture of Paecilomyces sinclairii.
AB  - AIMS: From a survey of submerged culture of edible mushrooms, a high pigment
      producing fungus Paecilomyces sinclairii was selected and its optimal culture
      conditions investigated. METHODS AND RESULTS: The optimal culture conditions for
      pigment production were as follows: inoculum age, 3 d; temperature, 25 degrees C;
      initial pH, 6.0; carbon source, 1.5% (w/v) soluble starch; nitrogen source, 1.5%
      (w/v) meat peptone. Although addition of 10 mmol l(-1) CaCl2 to the culture
      medium slightly increased pigment production, most of the bio-elements examined
      had no notable or detrimental effect on pigment production. CONCLUSIONS: Under
      the optimal conditions obtained in the flask culture tested, a ninefold increase
      in pigment production (4.4 g l(-1)) was achieved using a 5(-l) batch fermenter.
      Paecilomyces sinclairii secreted water-soluble red pigment into the culture
      medium. The pigment colour was strongly dependent on the pH of the solution: red
      at pH 3-4, violet at pH 5-9 and pink at pH 10-12. SIGNIFICANCE AND IMPACT OF THE
      STUDY: The high concentration of pigment (4.4 g l(-1)) produced by P. sinclairii
      demonstrates the possibility of commercial production of pigment by this strain,
      considering its relatively high production yield and light stability.

PMID- 12180941
TI  - Comparative study of in vitro methods used to analyse the activity of propolis
      extracts with different compositions against species of Candida.
AB  - AIMS: Propolis is known for its activity against micro-organisms and different in
      vitro assays have been used to evaluate this activity, frequently with
      contradictory results. METHODS AND RESULTS: Brazilian propolis from the state of
      Sao Paulo was extracted by maceration using different concentrations of ethanol
      and water. The resultant extracts were analysed by chromatographic methods.
      Several microbiological methods were compared to determine which one best
      evaluated the activity of the propolis extracts against species of Candida, with
      average minimal inhibitory concentration values between 6 and 12 mg ml(-1).
      CONCLUSIONS: Agar dilution in plates showed the clearest results. These were in
      agreement with the chromatographic analyses, which also identified the active
      substances. SIGNIFICANCE AND IMPACT OF THE STUDY: Although the active substances
      identified in this sample are typical of Brazilian propolis, their activity
      against Candida had not been recognized previously, demonstrating the importance
      of standardizing the correct combination of microbiological and chromatographic
      analyses.

PMID- 12180943
TI  - Zinc and glycerol enhance the production of nematicidal compounds in vitro and
      improve the biocontrol of Meloidogyne javanica in tomato by fluorescent
      pseudomonads.
AB  - AIMS: To assess the effects of various carbon and mineral sources on the
      nematicidal potential of biocontrol inoculants of Pseudomonas aeruginosa IE-6S+
      and Ps. fluorescens CHA0 under laboratory and glasshouse conditions. METHODS AND
      RESULTS: Culture filtrates of strains IE-6S+ and CHA0, cultured in nutrient yeast
      extract broth, caused substantial mortality of the juveniles of Meloidogyne
      javanica. The nematicidal activities of the culture filtrates were altered after
      amendment with various carbon and mineral sources. Soil amendment with zinc alone
      or in combination with glycerol improved the biocontrol efficacy against root
      knot nematode, promoted tomato plant growth and enhanced bacterial rhizosphere
      and endophytic colonization. CONCLUSIONS: Appropriate quantities of glycerol and
      zinc alone or in combination enhance the nematicidal activity of Ps. aeruginosa
      and Ps. fluorescens. Glucose reduces the activity of these bacteria against
      nematodes. SIGNIFICANCE AND IMPACT OF THE STUDY: Minerals and carbon sources are
      appealing because they are easy and economical to provide during liquid
      fermentation of inoculants or as fertilizer amendments to improve the biocontrol
      activity of indigenous and introduced bacteria.

PMID- 12180942
TI  - Fungicidal activity of essential oils of Cinnamomum zeylanicum (L.) and Syzygium
      aromaticum (L.) Merr et L.M. Perry against crown rot and anthracnose pathogens
      isolated from banana.
AB  - AIMS: To develop a post-harvest treatment system against post-harvest fungal
      pathogens of banana using natural products. METHODS AND RESULTS: Colletotrichum
      musae was isolated and identified as the causative agent responsible for
      anthracnose peel blemishes while three fungi, namely Lasiodiplodia theobromae, C.
      musae and Fusarium proliferatum, were identified as causative agents responsible
      for crown rot. During the liquid bioassay, cinnamon [Cinnamomum zeylanicum (L.)]
      leaf, bark and clove [Syzygium aromaticum (L.)] oils were tested against the
      anthracnose and crown rot pathogens. The test oils were fungistatic and
      fungicidal against the test pathogens within a range of 0.03-0.11% (v/v).
      CONCLUSIONS: Cinnamon and clove essential oils could be used as antifungal agents
      to manage post harvest fungal diseases of banana. SIGNIFICANCE AND IMPACT OF THE
      STUDY: Cinnamon and clove essential oil could be used as alternative post-harvest
      treatments on banana. Banana treated with essential oil is chemically safe and
      acceptable to consumers. Benomyl (Benlate), which is currently used to manage
      fungal pathogens, can cause adverse health effects and could be replaced with
      volatile essential oils.

PMID- 12180944
TI  - Isolation of Shiga toxin-producing Escherichia coli O103 from sheep using
      automated immunomagnetic separation (AIMS) and AIMS-ELISA: sheep as the source of
      a clinical E. coli O103 case?
AB  - AIMS: To investigate whether a sheep flock was the original reservoir of a Shiga
      toxin-producing Escherichia coli (STEC) O103 strain causing a clinical human case
      and to compare the two diagnostic methods automated immunomagnetic separation
      (AIMS) and AIMS-ELISA. METHODS AND RESULTS: AIMS detected Escherichia coli O103
      in 36.5% of the samples and AIMS-ELISA detected E. coli O103 in 52.1% of the
      samples. Polymerase chain reaction detected stx1 and eae in three of 109 E. coli
      O103 isolates. Pulsed field gel electrophoresis showed that the sheep and human
      STEC O103 were characterized by distinctly different profiles. CONCLUSIONS: The
      sheep flock was shown to carry STEC O103, although an association between the
      sheep flock and the clinical human case could neither be proven nor eliminated.
      Substantial agreement was found between AIMS and AIMS-ELISA, but AIMS-ELISA was
      less time consuming and resulted in a higher recovery of E. coli O103.
      SIGNIFICANCE AND IMPACT OF THE STUDY: The study shows that sheep may be carriers
      of STEC that are associated with human disease and that the methods described can
      be used to increase the sensitivity of STEC detection.

PMID- 12180946
TI  - Identification of genes involved in terbinafine resistance in Aspergillus
      nidulans.
AB  - AIMS: To determine the pattern and the genetic basis of resistance to
      terbinafine, a drug extensively used for the treatment of fungal infections in
      humans. METHODS AND RESULTS: Four resistant mutants from Aspergillus nidulans
      isolated after irradiation with ultraviolet light were crossed with the master
      strain F (MSF). Genetic analysis revealed that a single gene, located on
      chromosome IV, is responsible for resistance to terbinafine and that the alleles
      responsible for this resistance in these mutants are of a codominant or dominant
      nature at high terbinafine concentrations. Furthermore, the interaction of this
      mutation with another one identified on chromosome II causes the double mutant to
      be highly resistant. CONCLUSIONS: Periodic surveillance of antimycotic
      susceptibility would be an important measure in detecting the emergence and
      spread of resistance. Mutation in a single gene could be responsible for
      resistance to terbinafine and a genic interaction may be responsible for a higher
      level of antimycotic resistance. SIGNIFICANCE AND IMPACT OF THE STUDY: The
      understanding of the mechanisms that lead to changes in the sensitivity of a
      fungus to a given antifungal agent is important both in order to define
      strategies for the use of such agent and to guide the development of new
      antifungal agents.

PMID- 12180945
TI  - Analysis of a dextran-binding domain of the dextranase of Streptococcus mutans.
AB  - AIMS: To examine the dextran-binding domain of the dextranase (Dex) of
      Streptococcus mutans. METHODS AND RESULTS: Deletion mutants of the Dex gene of
      Strep. mutans were prepared by polymerase chain reaction and expressed in
      Escherichia coli cells. Binding of the truncated Dexs to dextran was measured
      with a Sephadex G-150 gel. Although the Dexs which lacked the N-terminal variable
      region lost enzyme activity, they still retained dextran-binding ability. In
      addition, further deletion into the conserved region from the N-terminal did not
      influence the dextran-binding ability. However, the Dex which carried a deletion
      in the C-terminus still possessed both enzyme activity and dextran-binding
      ability. Further deletion into the conserved region from the C-terminal resulted
      in complete disappearance of both enzyme and dextran-binding activities.
      CONCLUSIONS: Deletion analysis of the Dex gene of Strep. mutans showed that the C
      terminal side (about 120 amino acid residues) of the conserved region of the Dex
      was essential for dextran-binding ability. SIGNIFICANCE AND IMPACT OF THE STUDY:
      The dextran-binding domain was present in a different area from the catalytic
      site in the conserved region of the Dex molecule. The amino acid sequence of the
      dextran-binding domain of the Dex differed from those of glucan-binding regions
      of other glucan-binding proteins reported.

PMID- 12180947
TI  - Survival of Escherichia coli O157 in abattoir waste products.
AB  - AIMS: This study monitored survival and growth of Escherichia coli O157 in ovine
      and bovine abattoir waste. METHODS: Blood and gut contents were inoculated
      separately with cocktails of E. coli O157. Samples were stored aerophilically and
      microaerophilically at 5 degrees C, 15 degrees C and 30 degrees C to represent
      storage at different container depths and at extremes of UK ambient temperature.
      CONCLUSIONS: Results showed survival of E. coli O157 was irrespective of oxygen
      content with no significant differences observed between aerophilic and
      microaerophilic environments. Numbers of E. coli O157 in ovine and bovine gut
      contents showed no change when stored at 5 degrees C and increased 1-2 log(10) at
      15 degrees C and 30 degrees C in 28 h. In ovine and bovine blood, irrespective of
      storage temperature, there was a 0.5-2 log(10) reduction or no change in numbers
      except in ovine blood stored at 30 degrees C where the fall in numbers was
      followed by a 3 log(10) increase. In aged (stored at 4 degrees C for 18 h before
      spiking) bovine blood there was no significant change in numbers at 5 degrees C
      while at 15 degrees C there was 2 log(10) rise after 48 h. At 30 degrees C there
      was an initial 1 log(10) decrease in numbers followed by a 1 log(10) rise over
      the following 40 h. SIGNIFICANCE AND IMPACT OF STUDY: Abattoir wastes may become
      contaminated from animals infected with Verocytotoxigenic E. coli O157 and in
      certain storage conditions these pathogens could significantly increase in
      numbers. There is need for care in abattoir waste disposal, not only for
      personnel subject to direct contact, but also in the prevention of cross
      contamination to adjacent land and water courses which could indirectly infect
      humans.

PMID- 12180948
TI  - Association of pyrogenic exotoxin genes with pharyngitis and rheumatic
      fever/rheumatic heart disease among Indian isolates of Streptococcus pyogenes.
AB  - AIM: To monitor the presence of various pyrogenic exotoxin genes in strains of
      Streptococcus pyogenes isolated in India. METHODS & RESULTS: Isolates recovered
      from pharyngitis (52) and rheumatic fever (RF)/ rheumatic heart disease (RHD) (8)
      patients were analysed for the presence of toxin genes, speA, speB and speF, by
      PCR. The specificity of the products was confirmed by restriction enzyme
      digestion and Southern hybridization. Among the 60 isolates studied, the
      incidence of speA, speB and speF were 5(8.3%), 56(93.3%) and 53(88.3%),
      respectively. The expression of these genes was established in representative
      isolates by RT-PCR. CONCLUSIONS: Comparative analysis of frequency of the speA,
      speB and speF genes, among pharyngitis and RF/RHD associated isolates, showed
      higher incidence in RF/RHD (25%, 100%,100%) as compared to pharyngitis patients
      (5.8%, 92.3%, 86.5%), respectively. SIGNIFICANCE OF STUDY: The presence of the
      speA gene, which is usually associated with scarlet fever or toxic shock-like
      syndrome, within few Indian isolates may be indicative of new virulent strains
      circulating within the Indian community. High distribution of toxin genes among
      RF/RHD compared to pharyngitis isolates indicate their possible role in increased
      virulence.

PMID- 12180950
TI  - A RAPD-PCR genotyping assay which correlates with serotypes of group B
      streptococci.
AB  - AIMS: The purpose of this study was to determine if DNA polymorphisms generated
      by RAPD-PCR could be used to characterize Group B streptococci (GBS) for
      epidemiological purposes. METHODS AND RESULTS: 30 unrelated, previously serotyped
      strains were analysed by RAPD-PCR using two 10-mer primers (5' TGCGAGAGTC 3' and
      5' AGAGGGCACA 3'). Both primers generated DNA electropherotype patterns which, on
      analysis, clustered the isolates within their respective serotypes. A blind test
      of a further 3 field isolates also defined these strains within their
      subsequently determined serotypes. The detection of DNA polymorphisms between
      isolates within a serotype confirmed previous reports of the heterogenous nature
      of individual GBS serotypes. CONCLUSIONS: The RAPD-PCR is a potentially useful
      assay for the rapid characterization of neonatal infections associated with group
      B streptococci. The method appears to be more discriminatory than conventional
      serological assays. SIGNIFICANCE AND IMPACT OF THE STUDY: The RAPD-PCR assay is
      faster, more convenient and easier to perform than alternative DNA analytical
      procedures such as Pulsfield Gel Electrophoresis. We were able to reproduce the
      same results following re-testing of all isolates some 12 months later which
      suggests that the assay may be robust enough for use in routine epidemiological
      investigations.

PMID- 12180949
TI  - A highly selective direct method of detecting sulphate-reducing bacteria in crude
      oil.
AB  - AIMS: The aim of this work was to develop a highly selective method of detecting
      sulphate-reducing bacteria (SRB) in crude oil. METHODS: A pair of PCR primers was
      designed based on an alignment of the nucleotide sequence of the 16S rRNA genes
      from the Desulfovibrionaceae family. DNA extraction from crude oil was performed
      by the method using zirconia beads and a stool kit. RESULTS: The PCR specifically
      detected Desulfovibrio and Desulfomicrobium in a sediment sample. When nucleic
      acids extracted directly from crude oil were used for the PCR, 16S rRNA genes of
      Desulfovibrio and Thermodesulforhabdus norvegicus were detected. IMPACT OF STUDY:
      A simple direct method for detection of the SRB in crude oil using PCR was
      established.

PMID- 12180951
TI  - Detection of Proteobacteria from the rumen by PCR using methanotroph-specific
      primers.
AB  - AIMS: To detect Proteobacteria, including methanotrophs, from the rumen fluid and
      the bacteria inhabiting the rumen epithelium. METHODS AND RESULTS: Proteobacteria
      inhabiting the rumen were detected by PCR using methanotroph-specific primers.
      The detected Proteobacteria were divided into clusters A, B, and C in addition to
      one clone, which was distinct from the clusters and closely related to
      Nitrosomonas sp. The clusters A, B, and C were close to Succinivibrio
      dextrinosolvens, Enterobacter cloacae, and Actinobacillus minor, respectively.
      The clones obtained from the rumen fluid each belonged to cluster A or B. The
      clones obtained from the rumen epithelium belonged to cluster B or C or to
      Nitrosomonas sp. CONCLUSIONS: It has been assumed that the rumen fluid and the
      rumen epithelium host different populations of Proteobacteria. Moreover,
      detection of Nitrosomonas from the rumen epithelium would indicate the
      possibility that the bacterium oxidizes ammonia and methane on the rumen surface.
      SIGNIFICANCE AND IMPACT OF THE STUDY: These findings suggest that the rumen fluid
      and the epithelium support different microbial populations, which would play
      specific roles in rumen function. Future study should focus on the relationship
      between these communities and physiological functions in the rumen.

PMID- 12180952
TI  - Modulation of delayed-type hypersensitivity and acquired cellular resistance by
      orally administered viable indigenous lactobacilli in Listeria monocytogenes
      infected Wistar rats.
AB  - AIMS: Various probiotic lactobacilli have been reported to modulate immunity. In
      this study we investigate the effects of viable indigenous Lactobacillus strains
      Utr-1, Utr-2 and Utr-3, on T cell-mediated immunological memory responses.
      METHODS AND RESULTS: In Listeria monocytogenes infected rats it was demonstrated
      that short-term daily ingestion of Lactobacillus strain Utr-3 significantly
      decreased delayed-type hypersensitivity (DTH) expression, whereas long-term,
      daily oral administration of Lactobacillus strain Utr-3 and Lactobacillus strain
      Utr-2 significantly enhanced acquired cellular resistance (ACR) towards Listeria
      re-infection. CONCLUSIONS: Our findings demonstrate that certain indigenous
      Lactobacillus strains are capable of modulating T cell-mediated immunity.
      SIGNIFICANCE AND IMPACT OF THE STUDY: Our results support the importance of
      indigenous microflora analysis in probiotic lactobacilli studies.

PMID- 12180953
TI  - Cellobiose dehydrogenase production by Sclerotium species pathogenic to plants.
AB  - AIMS: Evaluation of various Sclerotium spp. as producers of the
      biotechnologically attractive enzyme cellobiose dehydrogenase. METHODS AND
      RESULTS: All isolates of S. coffeicola, S. delphinii and S. rolfsii grown in
      shaken flasks on a cellulose-based medium produced appreciable amounts of the
      extracellular enzyme cellobiose dehydrogenase. CONCLUSIONS: Cellobiose
      dehydrogenase seems to play an important role in phytopathogenic Sclerotium spp.;
      a possible function could be either in the degradation of rigid lignocellulose or
      as a protective mechanism against toxic quinones. SIGNIFICANCE AND IMPACT OF THE
      STUDY: S. coffeicola and S. delphinii were identified as potent, not-yet
      described producers of cellobiose dehydrogenase (CDH). The high levels of intact
      CDH produced by the different Sclerotium species should make them attractive
      producers for further studies and applications.

PMID- 12180954
TI  - Quantitative X-ray projection microscopy: phase-contrast and multi-spectral
      imaging.
AB  - We outline a new approach to X-ray projection microscopy in a scanning electron
      microscope (SEM), which exploits phase contrast to boost the quality and
      information content of images. These developments have been made possible by the
      combination of a high-brightness field-emission gun (FEG)-based SEM, direct
      detection CCD technology and new phase retrieval algorithms. Using this approach
      we have been able to obtain spatial resolution of < 0.2 micro m and have
      demonstrated novel features such as: (i) phase-contrast enhanced visibility of
      high spatial frequency image features (e.g. edges and boundaries) over a wide
      energy range; (ii) energy-resolved imaging to simultaneously produce multiple
      quasi-monochromatic images using broad-band polychromatic illumination; (iii)
      easy implementation of microtomography; (iv) rapid and robust phase/amplitude
      retrieval algorithms to enable new real-time and quantitative modes of
      microscopic imaging. These algorithms can also be applied successfully to recover
      object-plane information from intermediate-field images, unlocking the
      potentially greater contrast and resolution of the intermediate-field regime.
      Widespread applications are envisaged for fields such as materials science,
      biological and biomedical research and microelectronics device inspection. Some
      illustrative examples are presented. The quantitative methods described here are
      also very relevant to projection microscopy using other sources of radiation,
      such as visible light and electrons.

PMID- 12180955
TI  - Iso-butanol saturated water: a simple procedure for increasing staining intensity
      of resin sections for light and electron microscopy.
AB  - The addition of the alcohol iso-butanol (2-methylpropan-1-ol) to water was found
      to improve the post-staining procedures for semi-thin and ultrathin resin
      sections, for both light and electron microscopy. Stain penetration was enhanced
      with samples embedded in both acrylic and epoxy resins and provided structural
      information not previously seen. These improvements were found with general (non
      specific) stains and a fluorescence stain for light microscopy, as well as for a
      range of heavy metal stains for electron microscopy. The use of this
      water/solvent medium also gave improved results when used in a variety of
      immunogold labelling procedures, resulting in a greater specific label density
      without affecting background gold levels. The use of this solvent/water medium
      may have wider applications for other types of staining.

PMID- 12180956
TI  - Optic fibre bundle contact imaging probe employing a laser scanning confocal
      microscope.
AB  - A small diameter (600 micro m) fused optic fibre imaging bundle was used as a
      probe to compare fluorescent specimens by direct contact imaging using both a
      conventional fluorescence microscope and a laser scanning confocal microscope
      (LSCM) system. Green fluorescent polyester fibres placed on a green fluorescent
      cardboard background were used to model biological tissue. Axial displacement
      curves support the hypothesis that pinhole size in the LSCM system reduces the
      contribution of non-focal plane light. Qualitative comparison showed that the
      LSCM system produced superior image quality and contrast over the conventional
      system. The results indicate that the new LSCM-probe combination is an
      improvement over conventional fluorescence-probe systems. This study shows the
      feasibility of employing such a small diameter probe in the investigation of
      biological function in difficult to access areas.

PMID- 12180957
TI  - Measurement of magnetic domain wall width using energy-filtered Fresnel images.
AB  - Magnetic domain walls in Nd2Fe14B have been examined using a series of energy
      filtered Fresnel images in the field emission gun transmission electron
      microscope (FEGTEM). We describe the changes in the intensity distribution of the
      convergent wall image as a function of defocus, foil thickness and domain wall
      width. The effect of tilted domain walls and beam convergence on the fringe
      pattern is also discussed. A comparison of the experimental intensity profile
      with that from simulations allows the domain wall width to be determined.
      Measurement of very narrow walls is made possible only by using a relatively
      thick foil, which necessitates energy-filtering to allow quantitative comparison
      with simulations. The magnetic domain wall width in Nd2Fe14B was found to be 3 +/
      2 nm.

PMID- 12180958
TI  - Preparation of transmission electron microscopy cross-section specimens of crack
      tips using focused ion beam milling.
AB  - The preparation of transmission electron microscope (TEM) thin foil specimens
      from metal alloys containing cracks is usually thwarted by the difficulty in
      preventing preferential erosion of material along the flanks and at the tips of
      cracks. Recent developments in focused ion beam (FIB) micromachining methods have
      the potential to overcome this inherent problem. In this article we describe the
      development of new procedures, one using FIB alone and the other using a
      combination of FIB with more conventional ion milling to generate TEM specimens
      that largely retain the microstructural information at stress corrosion cracks in
      austentic alloys. Examples of corrosion product phase identification and
      interfacial segregation are included to verify that detailed information is not
      destroyed by ion bombardment during specimen preparation.

PMID- 12180959
TI  - Near real time in vivo fibre optic confocal microscopy: sub-cellular structure
      resolved.
AB  - We have built a fibre optic confocal reflectance microscope capable of imaging
      biological tissue in near real time. The measured lateral resolution is 3 micro m
      and axial resolution is 6 micro m. Images of epithelial cells, excised tissue
      biopsies, and the human lip in vivo have been obtained at 15 frames s-1. Both
      cell morphology and tissue architecture can be appreciated from images obtained
      with this microscope. This device has the potential to enable reflected light
      confocal imaging of internal organs for in situ detection of pathology.

PMID- 12180961
TI  - Image reconstruction by means of focus series.

PMID- 12180960
TI  - Amorphous solid water produced by cryosectioning of crystalline ice at 113 K.
AB  - Amorphous solid (vitreous) water can be obtained by a number of methods,
      including quick freezing of a very small volume of pure water, low pressure
      condensation of water vapour on a cold substrate or transformation of hexagonal
      ice (the ice which is naturally formed) under very high pressure at liquid
      nitrogen temperature. Larger volumes can be vitrified if cryoprotectant is added
      or when samples are frozen under high pressure. We show that a sample of 17.5%
      dextran solution or mouse brain tissue, respectively, frozen under high pressure
      (200 MPa) into cubic or hexagonal ice can be transformed into vitreous water by
      the very process of cryosectioning. The vitreous sections obtained by this
      procedure differ from cryosections obtained from vitreous samples by the
      irregular aspect of the sections and by small but significant differences in the
      electron diffraction patterns. For the growing community of cryo
      ultramicrotomists it is important to know that vitrification can occur at the
      knife edge. A vitreous sample is considered to show the best possible structural
      preservation. The sort of vitrification described here, however, can lead to bad
      structural preservation and is therefore considered to be a pitfall. Furthermore,
      we compare these sections with other forms of amorphous solid water and find it
      similar to high density amorphous water produced at very high pressures (about 1
      GPa) from hexagonal ice and annealed close to its transformation temperature at
      117 K.

PMID- 12180962
TI  - Stereological estimation of tubular length.
AB  - Very efficient and unbiased principles exist for estimating the total three
      dimensional (3D), two-dimensional and zero-dimensional amounts of arbitrary
      structure in 3D space. The total one-dimensional length of real structure, in the
      ordinary sense, is an abstraction from the point of view of integral geometry.
      All stereological estimators of 'tubular length' are thus approximations. In
      addition, they are riddled by biases due to several types of artificial edges and
      other practical problems. This paper discusses several of these and proposes
      practical solutions of minimal biases.

PMID- 12180963
TI  - Structures and mode of membrane interaction of a short alpha helical lytic
      peptide and its diastereomer determined by NMR, FTIR, and fluorescence
      spectroscopy.
AB  - The interaction of many lytic cationic antimicrobial peptides with their target
      cells involves electrostatic interactions, hydrophobic effects, and the formation
      of amphipathic secondary structures, such as alpha helices or beta sheets. We
      have shown in previous studies that incorporating approximately 30%d-amino acids
      into a short alpha helical lytic peptide composed of leucine and lysine preserved
      the antimicrobial activity of the parent peptide, while the hemolytic activity
      was abolished. However, the mechanisms underlying the unique structural features
      induced by incorporating d-amino acids that enable short diastereomeric
      antimicrobial peptides to preserve membrane binding and lytic capabilities remain
      unknown. In this study, we analyze in detail the structures of a model
      amphipathic alpha helical cytolytic peptide KLLLKWLL KLLK-NH2 and its
      diastereomeric analog and their interactions with zwitterionic and negatively
      charged membranes. Calculations based on high-resolution NMR experiments in
      dodecylphosphocholine (DPCho) and sodium dodecyl sulfate (SDS) micelles yield
      three-dimensional structures of both peptides. Structural analysis reveals that
      the peptides have an amphipathic organization within both membranes.
      Specifically, the alpha helical structure of the L-type peptide causes
      orientation of the hydrophobic and polar amino acids onto separate surfaces,
      allowing interactions with both the hydrophobic core of the membrane and the
      polar head group region. Significantly, despite the absence of helical
      structures, the diastereomer peptide analog exhibits similar segregation between
      the polar and hydrophobic surfaces. Further insight into the membrane-binding
      properties of the peptides and their depth of penetration into the lipid bilayer
      has been obtained through tryptophan quenching experiments using brominated
      phospholipids and the recently developed lipid/polydiacetylene (PDA) colorimetric
      assay. The combined NMR, FTIR, fluorescence, and colorimetric studies shed light
      on the importance of segregation between the positive charges and the hydrophobic
      moieties on opposite surfaces within the peptides for facilitating membrane
      binding and disruption, compared to the formation of alpha helical or beta sheet
      structures.

PMID- 12180965
TI  - Identification of hepatopoietin dimerization, its interacting regions and
      alternative splicing of its transcription.
AB  - Hepatopoietin (HPO) is a novel human hepatotrophic growth factor. Recently, we
      demonstrated that the extracellular ligand form of HPO can stimulate
      proliferation of hepatic cells via its specific receptor, which is on the surface
      of these cells. Also, the intracellular form of HPO potentiates the
      transcriptional factor AP-1. Intriguingly, a variety of HPO complexes with
      different molecular masses were detected in hepatocytes. In this study, we
      screened a human fetal liver cDNA library using the yeast two hybrid system with
      HPO as bait, hoping to find an HPO-binding protein. Surprisingly, HPO, itself,
      and a previously unidentified alternatively spliced form of HPO (named HPO23)
      were identified as interacting with HPO, indicating that HPO may exist as a
      homodimer or heterodimer. These results were further confirmed in vitro and in
      vivo. First, mass spectrometry analysis demonstrated that recombinant human HPO
      exist as a homodimer and that disulfide bonds were involved in the formation of
      rhHPO dimer. Secondly, a pull-down experiment confirmed that GST-HPO and HA-HPO,
      could bind together in vitro. Using HPO and various HPO deletion mutants, we
      identified the extreme 30 amino acids at both N- and C-termini are essential for
      HPO dimerization. Finally, Western blotting analysis demonstrated that HPO exists
      as two isoforms at 15 kDa and 23 kDa (HPO23) in liver cells, the 15 kDa species
      is located in nucleus, and the 23 kDa species mainly in the cytoplasm. These
      results implicated that the capacity of HPO to form both homodimers and
      heterodimers with the alternatively spliced forms might contribute to the
      existence of various HPO complexes in hepatic cells.

PMID- 12180964
TI  - Phosphorylation of Hrs downstream of the epidermal growth factor receptor.
AB  - The hepatocyte growth factor-regulated tyrosine kinase substrate Hrs is an early
      endosomal protein that is thought to play a regulatory role in the trafficking of
      growth factor/receptor complexes through early endosomes. Stimulation of cells
      with epidermal growth factor (EGF) rapidly leads to phosphorylation of Hrs,
      raising the question whether the receptor tyrosine kinase phosphorylates Hrs
      directly. Here, we present evidence that a downstream kinase, rather than the
      active receptor kinase is responsible. We show that the nonreceptor tyrosine
      kinase Src is able to phosphorylate Hrs in vitro and in vivo, but that Hrs is
      nevertheless phosphorylated in Src-, Yes- and Fyn-negative cells. Moreover, we
      show that only 10-20% of Hrs is phosphorylated following EGF stimulation, and
      that phosphorylation occurs at multiple tyrosines located in different parts of
      Hrs. These results suggest that Hrs is a substrate for several kinases downstream
      of the EGF receptor.

PMID- 12180966
TI  - Schemes of flux control in a model of Saccharomyces cerevisiae glycolysis.
AB  - We used parameter scanning to emulate changes to the limiting rate for steps in a
      fitted model of glucose-derepressed yeast glycolysis. Three flux-control regimes
      were observed, two of which were under the dominant control of hexose transport,
      in accordance with various experimental studies and other model predictions. A
      third control regime in which phosphofructokinase exerted dominant glycolytic
      flux control was also found, but it appeared to be physiologically unreachable by
      this model, and all realistically obtainable flux control regimes featured hexose
      transport as a step involving high flux control.

PMID- 12180967
TI  - Action of palytoxin on apical H+/K+-ATPase in rat colon.
AB  - Palytoxin stimulated a cation-dependent short-circuit current (Isc) in rat distal
      and proximal colon in a concentration-dependent fashion when applied to the
      mucosal surface of the tissue. The distal colon exhibited a higher sensitivity to
      the toxin. The palytoxin-induced Isc was blocked by vanadate but was resistant to
      ouabain or scilliroside, suggesting the conversion of a vanadate-sensitive H+/K+
      ATPase into an electrogenic cation transporter. Cation substitution experiments
      with basolaterally depolarized tissues suggested an apparent permeability of the
      palytoxin-induced conductance of Na+>K+>Li+. Immunohistochemical control
      experiments confirmed the absence of the Na+/K+-ATPase in the apical membrane.
      Consequently, the pore-forming action of palytoxin is not restricted to Na+/K+
      ATPase but is also observed with the colonic H+/K+-ATPase.

PMID- 12180968
TI  - A chloroplast RNA binding protein from stromal thylakoid membranes specifically
      binds to the 5' untranslated region of the psbA mRNA.
AB  - The intrachloroplastic localization of post-transcriptional gene expression steps
      represents one key determinant for the regulation of chloroplast development. We
      have characterized an RNA binding protein of 63 kDa (RBP63) from Chlamydomonas
      reinhardtii chloroplasts, which cofractionates with stromal thylakoid membranes.
      Solubility properties suggest that RBP63 is a peripheral membrane protein. Among
      RNA probes from different 5' untranslated regions of chloroplast transcripts,
      RBP63 preferentially binds to the psbA leader. This binding is dependent on a
      region comprising seven consecutive A residues, which is required for D1 protein
      synthesis. A possible role for this newly discovered RNA binding protein in
      membrane targeting of psbA gene expression is discussed.

PMID- 12180969
TI  - Characterization of scorpion alpha-like toxin group using two new toxins from the
      scorpion Leiurus quinquestriatus hebraeus.
AB  - Two novel toxins, Lqh6 and Lqh7, isolated from the venom of the scorpion Leiurus
      quinquestriatus hebraeus, have in their sequence a molecular signature (8Q/KPE10)
      associated with a recently defined group of alpha-toxins that target Na channels,
      namely the alpha-like toxins [reviewed in Gordon, D., Savarin, P., Gurevitz, M. &
      Zinn-Justin, S. (1998) J. Toxicol. Toxin Rev. 17, 131-159]. Lqh6 and Lqh7 are
      highly toxic to insects and mice, and inhibit the binding of alpha-toxins to
      cockroach neuronal membranes. Although they kill rodents by
      intracerebroventricular injection, they do not inhibit the binding of antimammal
      alpha-toxins (e.g. Lqh2) to rat brain synaptosomes, not even at high
      concentrations. Furthermore, in voltage-clamp experiments, rat brain Na channels
      IIA (rNav1.2A) expressed in Xenopus oocytes are not affected by Lqh6 nor by Lqh7
      below 3 micro m. In contrast, muscular Na channels (rNav1.4 and hNav1.5)
      expressed in the same cells respond to nanomolar concentrations of Lqh6 and Lqh7
      by slowing of Na current inactivation and a leftward shift of the peak
      conductance-voltage curve. The structural and pharmacological properties of the
      new toxins are compared to those of other scorpion alpha-toxins in order to re
      examine the hallmarks previously set for the alpha-like toxin group.

PMID- 12180970
TI  - A cocaine insensitive chimeric insect serotonin transporter reveals domains
      critical for cocaine interaction.
AB  - Serotonin transporters are key target sites for clinical drugs and
      psychostimulants, such as fluoxetine and cocaine. Molecular cloning of a
      serotonin transporter from the central nervous system of the insect Manduca sexta
      enabled us to define domains that affect antagonist action, particularly cocaine.
      This insect serotonin transporter transiently expressed in CV-1 monkey kidney
      cells exhibits saturable, high affinity Na+ and Cl- dependent serotonin uptake,
      with estimated Km and Vmax values of 436 +/- 19 nm and 3.8 +/- 0.6 x 10-18
      mol.cell.min-1, respectively. The Manduca high affinity Na+/Cl- dependent
      transporter shares 53% and 74% amino acid identity with the human and fruit fly
      serotonin transporters, respectively. However, in contrast to serotonin
      transporters from these two latter species, the Manduca transporter is inhibited
      poorly by fluoxetine (IC50 = 1.23 micro m) and cocaine (IC50 = 12.89 micro m). To
      delineate domains and residues that could play a role in cocaine interaction, the
      human serotonin transporter was mutated to incorporate unique amino acid
      substitutions, detected in the Manduca homologue. We identified a domain in
      extracellular loop 2 (amino acids 148-152), which, when inserted into the human
      transporter, results in decreased cocaine sensitivity of the latter (IC50 = 1.54
      micro m). We also constructed a number of chimeras between the human and Manduca
      serotonin transporters (hSERT and MasSERT, respectively). The chimera, hSERT1
      146/MasSERT106-587, which involved N-terminal swaps including transmembrane
      domains (TMDs) 1 and 2, was remarkably insensitive to cocaine (IC50 = 180 micro
      m) compared to the human (IC50 = 0.431 micro m) and Manduca serotonin
      transporters. The chimera MasSERT1-67/hSERT109-630, which involved only the TMD1
      swap, showed greater sensitivity to cocaine (IC50 = 0.225 micro m) than the human
      transporter. Both chimeras showed twofold higher serotonin transport affinity
      compared to human and Manduca serotonin transporters. Our results show TMD1 and
      TMD2 affect the apparent substrate transport and antagonist sensitivity by
      possibly providing unique conformations to the transporter. The availability of
      these chimeras facilitates elucidation of specific amino acids involved in
      interactions with cocaine.

PMID- 12180972
TI  - Thermodynamic stability of porcine beta-lactoglobulin. A structural relevance.
AB  - The proposed biological function of beta-lactoglobulins as transporting proteins
      assumes a binding ability for ligands and high stability under the acidic
      conditions of the stomach. This work shows that the conformational stability of
      nonruminant porcine beta-lactoglobulin (BLG) is not consistent with this
      hypothesis. Thermal denaturation of porcine BLG was studied by high-sensitivity
      differential scanning calorimetry within the pH range 2.0-10.0. Dependences of
      the denaturation temperature and enthalpy on pH were obtained, which reveal a
      substantial decrease in both parameters in acidic and basic media. The
      denaturation enthalpy follows a linear dependence on the denaturation
      temperature. The slope of this line is 9.4 +/- 0.6 kJ.mol-1. K-1,which is close
      to the denaturation heat capacity increment DeltadCp = 9.6 +/- 0.5 kJ.mol-1.K-1,
      determined directly from the thermograms. At pH 6.25 the denaturation
      temperatures of porcine and bovine BLG coincide, at 83.2 degrees C. At this pH
      the denaturation enthalpy of porcine BLG is 300 kJ.mol-1. The denaturation
      transition of porcine BLG was shown to be reversible at pH 3.0 and pH 9.0. The
      transition profile at both pH values follows the two-state model of denaturation.
      Based on the pH-dependence of the transition temperature and the linear
      temperature dependence of the transition enthalpy, the excess free energy of
      denaturation, DeltadGE, of porcine BLG was calculated as a function of pH and
      compared with that of bovine BLG derived from previously reported data. The pH
      dependence of DeltadGE is analysed in terms of the contributions of side-chain H
      bonds to the protein stability. Interactions stabilizing native folds of porcine
      and bovine BLG are discussed.

PMID- 12180971
TI  - Suppression of urokinase receptor expression by bikunin is associated with
      inhibition of upstream targets of extracellular signal-regulated kinase-dependent
      cascade.
AB  - Our laboratory showed that bikunin, a Kunitz-type protease inhibitor, suppresses
      4beta-phorbol 12-myristate 13-acetate (PMA)- or tumor necrosis factor-alpha
      (TNFalpha)-induced urokinase-type plasminogen activator (uPA) expression in
      different cell types. In addition to its effects on protease inhibition, bikunin
      could be modulating other cellular events associated with the metastatic cascade.
      To test this hypothesis, we examined whether bikunin was able to suppress the
      expression of uPA receptor (uPAR) mRNA and protein in a human chondrosarcoma cell
      line, HCS-2/8, and two human ovarian cancer cell lines, HOC-I and HRA. The
      present study showed that (a) bikunin suppresses the expression of constitutive
      and PMA-induced uPAR mRNA and protein in a variety of cell types; (b) an
      extracellular signal-regulated kinase (ERK) activation system is necessary for
      the PMA-induced increase in uPAR expression, as PD098059 and U0126, which prevent
      the activation of MEK1, reduce the uPAR expression; (c) bikunin markedly
      suppresses PMA-induced phosphorylation of ERK1/2 at the concentration that
      prevents uPAR expression, but does not reduce total ERK1/2 antigen level; (d)
      bikunin has no ability to inhibit overexpression of uPAR in cells treated with
      sodium vanadate; and (e) we further studied the inhibition of uPAR expression by
      stable transfection of HRA cells with bikunin gene, demonstrating that bikunin
      secretion is necessary for inhibition of uPAR expression. We conclude that
      bikunin downregulates constitutive and PMA-stimulated uPAR mRNA and protein
      possibly through suppression of upstream targets of the ERK-dependent cascade,
      independent of whether cells were treated with exogenous bikunin or transfected
      with bikunin gene.

PMID- 12180973
TI  - In vitro and in vivo self-cleavage of Streptococcus pneumoniae signal peptidase
      I.
AB  - We have previously demonstrated that Streptococcus pneumoniae signal peptidase
      (SPase) I catalyzes a self-cleavage to result in a truncated product, SPase37-204
      [Peng, S.B., Wang, L., Moomaw, J., Peery, R.B., Sun, P.M., Johnson, R.B., Lu, J.,
      Treadway, P., Skatrud, P.L. & Wang, Q.M. (2001) J. Bacteriol.183, 621-627]. In
      this study, we investigated the effect of phospholipid on invitro self-cleavage
      of S. pneumoniae SPase I. In the presence of phospholipid, the self-cleavage
      predominantly occurred at one cleavage site between Gly36-His37, whereas the self
      cleavage occurred at multiple sites in the absence of phospholipid, and two
      additional self-cleavage sites, Ala65-His66 and Ala143-Phe144, were identified.
      All three self-cleavage sites strongly resemble the signal peptide cleavage site
      and follow the (-1, -3) rule for SPase I recognition. Kinetic analysis
      demonstrated that self-cleavage is a concentration dependent and intermolecular
      event, and the activity in the presence of phospholipid is 25-fold higher than
      that in the absence of phospholipid. Biochemical analysis demonstrated that
      SPase37-204, the major product of the self-cleavage totally lost activity to
      cleave its substrates, indicating that the self-cleavage resulted in the
      inactivation of the enzyme. More importantly, the self-cleavage was demonstrated
      to be happening in vivo in all the growth phases of S. pneumoniae cells. The
      bacterial cells keep the active SPase I at the highest level in exponential
      growth phase, suggesting that the self-cleavage may play an important role in
      regulating the activity of the enzyme under different conditions.

PMID- 12180974
TI  - Leishmania donovani phosphofructokinase. Gene characterization, biochemical
      properties and structure-modeling studies.
AB  - The characterization of the gene encoding Leishmania donovani phosphofructokinase
      (PFK) and the biochemical properties of the expressed enzyme are reported. L.
      donovani has a single PFK gene copy per haploid genome that encodes a polypeptide
      with a deduced molecular mass of 53 988 and a pI of 9.26. The predicted amino
      acid sequence contains a C-terminal tripeptide that conforms to an established
      signal for glycosome targeting. L. donovani PFK showed most sequence similarity
      to inorganic pyrophosphate (PPi)-dependent PFKs, despite being ATP-dependent. It
      thereby resembles PFKs from other Kinetoplastida such as Trypanosoma brucei,
      Trypanoplasma borreli (characterized in this study), and a PFK found in Entamoeba
      histolytica. It exhibited hyperbolic kinetics with respect to ATP whereas the
      binding of the other substrate, fructose 6-phosphate, showed slight positive
      cooperativity. PPi, even at high concentrations, did not have any effect. AMP
      acted as an activator of PFK, shifting its kinetics for fructose 6-phosphate from
      slightly sigmoid to hyperbolic, and increasing considerably the affinity for this
      substrate, whereas GDP did not have any effect. Modelling studies and site
      directed mutagenesis were employed to shed light on the structural basis for the
      AMP effector specificity and on ATP/PPi specificity among PFKs.

PMID- 12180975
TI  - Detecting mitochondrial permeability transition by confocal imaging of intact
      cells pinocytically loaded with calcein.
AB  - When studied in vitro, mitochondrial permeability transition (MPT) is associated
      with an increase in mitochondrial permeability to solutes up to 1500 Da in mass
      and a loss of electrical potential difference across the inner mitochondrial
      membrane (Deltapsimit). The MPT has been implicated as being important in
      cellular calcium homeostasis, autophagy and cell death via necrosis and
      apoptosis. Thus, it is important to develop a valid technique for accurate
      measurement of this phenomenon in intact cells. We developed a procedure for the
      detection of MPT in intact cells that avoids the disadvantages associated with
      earlier approaches. In this new technique, unmodified (green-fluorescent) calcein
      is simultaneously introduced into the cytosol of millions of cells by the process
      of pinocytic loading and, to identify the position of individual mitochondria and
      to measure Deltapsimit, the cells are counter-stained with a red-fluorescing
      potentiometric dye. Using this approach with a variety of cell types, we
      demonstrate that cytosolic calcein is excluded from normal polarized mitochondria
      but enters them during MPT. This technique may be valuable in studies
      investigating the cellular functions of MPT.

PMID- 12180976
TI  - A sucrose-binding protein homologue from soybean exhibits GTP-binding activity
      that functions independently of sucrose transport activity.
AB  - The sucrose binding protein (SBP) has been implicated as an important component
      of the sucrose uptake system in plants. SBP-mediated sucrose transport displays
      unique kinetic features and the protein is not similar to other transport
      proteins. Here, we report the characterization of a member of the SBP family from
      soybean [Glycine max (L) Merrill] designated S64 or SBP2. Subcellular
      fractionation and precipitation by GTP-agarose demonstrated that S64/SBP2 is a
      membrane-associated protein that exhibits GTP binding activity. Purified
      recombinant S64/SBP2 protein, expressed as a histidine-tagged protein in
      Escherichia coli, exhibited nucleotide-binding specificity to guanine
      nucleotides. The GTP binding site was mapped to an imperfect Walker A type
      sequence, Ala279-Leu-Ala-Pro-Thr-Lys-Lys-Ser286, by site-directed mutagenesis.
      Escherichia coli-produced wild-type protein and a truncated version of the
      protein containing the putative binding-sequence-bound GTP, although not with the
      same efficiency. In contrast, replacement of Thr283 and Lys284 residues to Leu
      and Glu residues prevented GTP binding. The site directed mutant failed to bind
      GTP but retained the ability to undergo oligomerization andto promote growth of
      the susy7 yeast strain, deficient inutilizing extracellular sucrose, on medium
      containing sucrose as the sole carbon source. Our results indicate that GTP
      binding and sucrose transport by SBP are separable and function independently.
      The implications of our findings with respect to the function and membrane
      topology of SBP are discussed.

PMID- 12180977
TI  - Identification and structural characterization of a sialylated lacto-N
      neotetraose structure in the lipopolysaccharide of Haemophilus influenzae.
AB  - A sialylated lacto-N-neotetraose (Sial-lNnT) structural unit was identified and
      structurally characterized in the lipopolysaccharide (LPS) from the genome
      sequenced strain Rd [corrected] (RM118) of the human pathogen Haemophilus
      influenzae grown in the presence of sialic acid. A combination of molecular
      genetics, MS and NMR spectroscopy techniques showed that this structural unit
      extended from the proximal heptose residue of the inner core region of the LPS
      molecule. The structure of the Sial-lNnT unit was identical to that found in
      meningococcal LPS, but glycoforms containing truncations of the Sial-lNnT unit,
      comprising fewer residues than the complete oligosaccharide component, were not
      detected. The finding of sialylated glycoforms that were either fully extended or
      absent suggests a novel biosynthetic feature for adding the terminal
      tetrasaccharide unit of the Sial-lNnT to the glycose acceptor at the proximal
      inner core heptose.

PMID- 12180978
TI  - NADH oxidation and NAD+ reduction catalysed by tightly coupled inside-out
      vesicles from Paracoccus denitrificans.
AB  - Tightly coupled inside-out vesicles were prepared from Paracoccus denitrificans
      cells (SPP, sub-Paracoccus particles) and characterized kinetically. The rate of
      NADH oxidation, catalysed by SPP, increases 6-8 times on addition of gramicidin.
      The vesicles are capable of catalysing Delta micro H+-dependent reverse electron
      transfer from quinol to NAD+. The kinetic parameters of the NADH-oxidase and the
      reverse electron transfer carried out by membrane-bound P. denitrificans complex
      I were estimated and compared with those of the mitochondrial enzyme. The data
      demonstrate that catalytic properties of the dinucleotide-binding site of the
      bacterial and mitochondrial complex I are almost identical, pointing out similar
      organization of the site in mammals and P. denitrificans. Inhibition of the
      bacterial complex I by a specific inhibitor of Q reduction, rotenone, is very
      different from that of the mitochondrial enzyme. The inhibitor is capable of
      suppressing the NADH oxidation reaction only at micromolar concentrations, while
      the activity of mitochondrial enzyme is suppressed by nanomolar concentrations of
      rotenone. In contrast to the mitochondrial enzyme, rotenone, even at
      concentrations as high as 10 micro m, does not inhibit the reverse, Delta micro
      H+-dependent NAD+-reductase reaction on SPP.

PMID- 12180979
TI  - Cellular uptake of antisense oligonucleotides after complexing or conjugation
      with cell-penetrating model peptides.
AB  - The uptake by mammalian cells of phosphorothioate oligonucleotides was compared
      with that of their respective complexes or conjugates with cationic, cell
      penetrating model peptides of varying helix-forming propensity and
      amphipathicity. An HPLC-based protocol for the synthesis and purification of
      disulfide bridged conjugates in the 10-100 nmol range was developed. Confocal
      laser scanning microscopy (CLSM) in combination with gel-capillary
      electrophoresis and laser induced fluorescence detection (GCE-LIF) revealed
      cytoplasmic and nuclear accumulationin all cases. The uptake differences between
      naked oligonucleotides and their respective peptide complexes or conjugates were
      generally confined to one order of magnitude. No significant influence of the
      structural properties of the peptide components upon cellular uptake was found.
      Our results question the common belief that the increased biological activity of
      oligonucleotides after derivatization with membrane permeable peptides may be
      primarily due to improved membrane translocation.

PMID- 12180980
TI  - ISC1-encoded inositol phosphosphingolipid phospholipase C is involved in Na+/Li+
      halotolerance of Saccharomyces cerevisiae.
AB  - In Saccharomyces cerevisiae, toxic concentrations of Na+ orLi+ ions induce the
      expression of the cation-extrusion ATPase gene, ENA1. Several well-studied signal
      transduction pathways are known correlating high salinity to the transcriptional
      activation of ENA1. Nevertheless, information on the actual sensing mechanism
      initiating these pathways is limited. Here, we report that the ISC1-encoded
      phosphosphingolipid-specific phospholipase C appears to be involved in
      stimulation of ENA1 expression and, consequently, in mediating Na+ and Li+
      tolerance in yeast. Deletion of ISC1 distinctly decreased cellular Na+ and Li+
      tolerance as growth of the Deltaisc1::HIS5 mutant, DZY1, was severely impaired by
      0.5 m NaCl or 0.01 m LiCl. In contrast,K+ tolerance and general osmostress
      regulation wereunaffected. Isc1Delta mutant growth with 0.9 m KCl and glycerol
      accumulation in the presence of 0.9 m NaCl or 1.5 m sorbitol were comparable to
      that of the wild-type. ENA1-lacZ reporter studies suggested that the increased
      salt sensitivity of the isc1Delta mutant is related to a significant reduction of
      Na+/Li+-stimulated ENA1 expression. Correspondingly, Ena1p-dependent extrusion of
      Na+/Li+ ions was less efficient in the isc1Delta mutant than in wild-type cells.
      Itis suggested that ISC1-dependent hydrolysis of an unidentified yeast inositol
      phosphosphingolipid represents an early event in one of the salt-induced
      signalling pathways of ENA1 transcriptional activation.

PMID- 12180981
TI  - Cloning of a rat gene encoding the histo-blood group A enzyme. Tissue expression
      of the gene and of the A and B antigens.
AB  - The complete coding sequence of a BDIX rat gene homologous to the human ABO gene
      was determined. Identification of the exon-intron boundaries, obtained by
      comparison of the coding sequence with rat genomic sequences from data banks,
      revealed that the rat gene structure is identical to that of the human ABO gene.
      It localizes to rat chromosome 3 (q11-q12), a region homologous to human 9q34.
      Phylogenetic analysis of a set of sequences available for the various members of
      the same gene family confirmed that the rat sequence belongs to the ABO gene
      cluster. The cDNA was transfected in CHO cells already stably transfected with an
      alpha1,2fucosyltransferase in order to express H oligosaccharide acceptors.
      Analysis of the transfectants by flow cytometry indicated that A but not B
      epitopes were synthesized. Direct assay of the enzyme activity using 2'
      fucosyllactose as acceptor confirmed the strong UDP
      GalNAc:Fucalpha1,2GalalphaGalNAc transferase (Atransferase) activity of the
      enzyme product and allowed detection of a small UDP-Gal:Fucalpha1,2GalalphaGal
      transferase (B transferase) activity. The presence of the mRNA and of the A and B
      antigens was searched in various BDIX rat tissues. There was a general good
      concordance between the presence of the mRNA and that of the A antigen. Tissue
      distributions of the A and B antigens in the homozygous BDIX rat strain were
      largely different, indicating that these antigens cannot be synthesized by
      alleles of the same gene in this rat inbred strain.

PMID- 12180982
TI  - Xanthosine and xanthine. Substrate properties with purine nucleoside
      phosphorylases, and relevance to other enzyme systems.
AB  - Substrate properties of xanthine (Xan) and xanthosine (Xao) for purine nucleoside
      phosphorylases (PNP) of mammalian origin have been reported previously, but only
      at a single arbitrarily selected pH and with no kinetic constants. Additionally,
      studies have not taken into account the fact that, at physiological pH, Xao (pKa
      = 5.7) is a monoanion, while Xan (pKa = 7.7) is an equilibrium mixture of the
      neutral and monoanionic forms. Furthermore the monoanionic forms, unlike those of
      guanosine (Guo) and inosine (Ino), and guanine (Gua) and hypoxanthine (Hx), are
      still 6-oxopurines. The optimum pH for PNP from human erythrocytes and calf
      spleen with both Xao and Xan is in the range 5-6, whereas those with Guo and Gua,
      and Ino and Hx, are in the range 7-8. The pH-dependence of substrate properties
      of Xao and Xan points to both neutral and anionic forms as substrates, with a
      marked preference for the neutral species. Both neutral and anionic forms of 6
      thioxanthine (pKa = 6.5 +/- 0.1), but not of 2-thioxanthine (pKa = 5.9 +/- 0.1),
      are weaker substrates. Phosphorolysis of Xao to Xan by calf spleen PNP at pH 5.7
      levels off at 83% conversion, due to equilibrium with the reverse synthetic
      pathway (equilibrium constant 0.05), and not by product inhibition. Replacement
      of Pi by arsenate led to complete arsenolysis of Xao. Kinetic parameters are
      reported for the phosphorolytic and reverse synthetic pathways at several
      selected pH values. Phosphorolysis of 200 micro m Xao by the human enzyme at pH
      5.7 is inhibited by Guo (IC50 = 10 +/- 2 micro m), Hx (IC50 = 7 +/- 1 micro m)
      and Gua (IC50 = 4.0 +/- 0.2 micro m). With Gua, inhibition was shown to be
      competitive, with Ki = 2.0 +/- 0.3 micro m. By contrast, Xao and its products of
      phosphorolysis (Xan and R1P), were poor inhibitors of phosphorolysis of Guo, and
      Xan did not inhibit the reverse reaction with Gua. Possible modes of binding of
      the neutral and anionic forms of Xan and Xao by mammalian PNPs are proposed.
      Attention is directed to the fact that the structural properties of the neutral
      and ionic forms of XMP, Xao and Xan are also of key importance in many other
      enzyme systems, such as IMP dehydrogenase, some nucleic acid polymerases,
      biosynthesis of caffeine and phosphoribosyltransferases.

PMID- 12180983
TI  - Characterization of the 5' untranslated region of alpha and beta isoforms of the
      human thromboxane A2 receptor (TP). Differential promoter utilization by the TP
      isoforms.
AB  - In humans, thromboxane (TX) A2 signals through two TXA2 receptor (TP) isoforms,
      TPalpha and TPbeta, that diverge within their carboxyl terminal cytoplasmic (C)
      tail regions and arise by differential splicing. The human TP gene contains three
      exons E1-E3; while E1 exclusively encodes 5' untranslated region (UTR) sequence,
      E2 and E3 represent the main coding exons. An additional noncoding exon, E1b was
      identified within intron 1. Additionally, the TP gene contains two promoters P1
      and P2 located 5' of E1 and E1b, respectively. Herein, we investigated the
      molecular basis of the differential expression of the TP isoforms by
      characterizing the 5' UTR of the TP transcripts. While E1 and E1b were found
      associated with TP transcript(s), their expression was mutually exclusive. 5'
      rapid amplification of cDNA ends (5' RACE) established that the major
      transcription initiation (TI) sites were clustered between -115 and -92 within E1
      and at -99 within E1b. While E1 and E1b sequences were identified on TPalpha
      transcript(s), neither existed on TPbeta transcript(s). More specifically,
      TPalpha and TPbeta transcripts diverged within E2 and the major TI sites for
      TPbeta transcripts mapped to -12/-15 therein. Through genetic reporter assays, a
      previously unrecognized promoter, termed P3, was identified on the TP gene
      located immediately 5' of -12. The proximity of P3 to the TI site of TPbeta
      suggests a role for P3 in the control of TPbeta expression and implies that
      TPalpha and TPbeta, in addition to being products of differential splicing, are
      under the transcriptional control of distinct promoters.

PMID- 12180984
TI  - Functional characterization of the maltose ATP-binding-cassette transporter of
      Salmonella typhimurium by means of monoclonal antibodies directed against the
      MalK subunit.
AB  - The maltose ATP-binding cassette transporter of Salmonella typhimurium is
      composed of a membrane-associated complex (MalFGK2) and a periplasmic receptor
      (MalE). In addition to its role in transport, the complex acts as a repressor of
      maltose-regulated gene expression and is subject to inhibition in the process of
      inducer exclusion. These activities are thought to be mediated by interactions of
      the ATPase subunit, MalK, with the transcriptional activator, MalT, and
      nonphosphorylated enzyme IIA of the glucose phosphotransferase system,
      respectively. To gain further insight in protein regions that are critical for
      these functions, we have generated nine MalK-specific monoclonal antibodies.
      These bind to four nonoverlapping linear epitopes: 60-LFig-63 (5B5), 113
      RVNQVAEVLQL-123 (represented by 4H12), 309-GHETQI-314 (2F9) and 352-LFREDGSACR
      361 (represented by 4B3). All mAbs recognize their epitopes in soluble MalK and
      in the MalFGK2 complex with Kd values ranging from 10-6 to 10-8 m. ATP reduced
      the affinity of the mAbs for soluble MalK, indicating a conformational change
      that renders the epitopes less accessible. 4H12 and 5B5 inhibit the ATPase
      activity of MalK and the MalE/maltose-stimulated ATPase activity of
      proteoliposomes, while their Fab fragments displayed no significant effect. The
      results suggest a similar solvent-exposed position of helix 3 in the MalK dimer
      and in the intact complex and might argue against a direct role in the catalytic
      process. 4B3 and 2F9 exhibit reduced binding to the MalFGK2 complex in the
      presence of MalT and enzyme IIAGlc, respectively, thereby providing the first
      direct evidence for the C-terminal domain of MalK being the site of interaction
      with the regulatory proteins.

PMID- 12180985
TI  - Domains of ERRgamma that mediate homodimerization and interaction with factors
      stimulating DNA binding.
AB  - The estrogen receptor-related receptor gamma (ERRgamma/ERR3/NR3B3) is an orphan
      member of the nuclear receptor superfamily closely related to the estrogen
      receptors. To explore the DNA binding characteristics, the protein-DNA
      interaction was studied in electrophoretic mobility shift assays (EMSAs). In
      vitro translated ERRgamma binds as a homodimer to direct repeats (DR) without
      spacing of the nuclear receptor half-site 5'-AGGTCA-3' (DR-0), to extended half
      sites, and to the inverted estrogen response element. Using ERRgamma deletion
      constructs, binding was found to be dependent on the presence of sequences in the
      ligand binding domain (LBD). A far-Western analysis revealed that ERRgamma forms
      dimers even in the absence of DNA. Two elements, located in the hinge region and
      in the LBD, respectively, are necessary for DNA-independent dimerization. DNA
      binding of bacterial expressed ERRgamma requires additional factors present in
      the serum and in cellular extracts. Fusion proteins of the germ cell nuclear
      factor (GCNF/NR6A1) with ERRgamma showed that the characteristic feature to be
      stimulated by additional factors can be transferred to a heterologous protein.
      The stimulating activity was further characterized and its target sequence
      narrowed down to a small element in the hinge region.

PMID- 12180986
TI  - Redox reaction between amino-(3,4-dihydroxyphenyl)methyl phosphonic acid and
      dopaquinone is responsible for the apparent inhibitory effect on tyrosinase.
AB  - Amino-(3,4-dihydroxyphenyl)methyl phosphonic acid, the phosphonic analog of 3,4
      dihydroxyphenylglycine, had been previously reported as a potent inhibitor of
      tyrosinase. The mechanism of the apparent enzyme inhibition by this compound has
      now been established. Amino-(3,4-dihydroxyphenyl)methyl phosphonic acid turned
      out to be a substrate and was oxidized to o-quinone, which evolved to a final
      product identified as 3,4-dihydroxybenzaldehyde, the same as for 3,4
      dihydroxyphenylglycine. Monohydroxylated compounds (amino-(3-hydroxyphenyl)methyl
      phosphonic acid and amino-(4-hydroxyphenyl)methyl phosphonic acid) were not
      oxidized, neither was 4-hydroxy-l-phenylglycine. However, the relatively high Km
      for amino-(3,4-dihydroxyphenyl)methyl phosphonic acid (0.52 mm) indicated that
      competitive inhibition could not entirely explain the previously reported strong
      inhibitory effect (Ki = 50 and 97 micro m for tyrosine and 3-(3,4
      dihydroxyphenyl)alanine (Dopa) as substrates, respectively). Neither was the
      enzyme covalently inactivated to a significant degree. Spectroscopic and
      electrochemical analysis of the oxidation of a mixture of Dopa and the inhibitor
      demonstrated that the phosphonic compound reduced dopaquinone back to Dopa, thus
      diminishing and delaying the formation of dopachrome. This produces an apparent
      strong inhibitory effect when the reaction is monitored spectrophotometrically at
      475 nm. In this peculiar case Dopa acts as a redox shuttle mediating the
      oxidation of the shorter phosphonic homolog. Decomposition of the phosphonic o
      quinone to 3,4-dihydroxybenzaldehyde drives the reaction against the slightly
      unfavorable difference in redox potentials.

PMID- 12180987
TI  - Cloning and functional characterization of Phaeodactylum tricornutum front-end
      desaturases involved in eicosapentaenoic acid biosynthesis.
AB  - Phaeodactylum tricornutum is an unicellular silica-less diatom in which
      eicosapentaenoic acid accumulates up to 30% of the total fatty acids. This marine
      diatom was used for cloning genes encoding fatty acid desaturases involved in
      eicosapentaenoic acid biosynthesis. Using a combination of PCR, mass sequencing
      and library screening, the coding sequences of two desaturases were identified.
      Both protein sequences contained a cytochrome b5 domain fused to the N-terminus
      and the three histidine clusters common to all front-end fatty acid desaturases.
      The full length clones were expressed in Saccharomyces cerevisiae and
      characterized as Delta5- and Delta6-fatty acid desaturases. The substrate
      specificity of each enzyme was determined and confirmed their involvement in
      eicosapentaenoic acid biosynthesis. Using both desaturases in combination with
      the Delta6-specific elongase from Physcomitrella patens, the biosynthetic
      pathways of arachidonic and eicosapentaenoic acid were reconstituted in yeast.
      These reconstitutions indicated that these two desaturases functioned in the
      omega3- and omega6-pathways, in good agreement with both routes coexisting in
      Phaeodactylum tricornutum. Interestingly, when the substrate selectivity of each
      enzyme was determined, both desaturases converted the omega3- and omega6-fatty
      acids with similar efficiencies, indicating that none of them was specific for
      either the omega3- or the omega6-pathway. To our knowledge, this is the first
      report describing the isolation and biochemical characterization of fatty acid
      desaturases from diatoms.

PMID- 12180988
TI  - Effect of sequence polymorphism and drug resistance on two HIV-1 Gag processing
      sites.
AB  - The HIV-1 proteinase (PR) has proved to be a good target for antiretroviral
      therapy of AIDS, and various PR inhibitors are now in clinical use. However,
      there is a rapid selection of viral variants bearing mutations in the proteinase
      that are resistant to clinical inhibitors. Drug resistance also involves
      mutations of the nucleocapsid/p1 and p1/p6 cleavage sites of Gag, both in vitro
      and in vivo. Cleavages at these sites have been shown to be rate limiting steps
      for polyprotein processing and viral maturation. Furthermore, these sites show
      significant sequence polymorphism, which also may have an impact on virion
      infectivity. We have studied the hydrolysis of oligopeptides representing these
      cleavage sites with representative mutations found as natural variations or that
      arise as resistant mutations. Wild-type and five drug resistant PRs with
      mutations within or outside the substrate binding site were tested. While the
      natural variations showed either increased or decreased susceptibility of
      peptides toward the proteinases, the resistant mutations always had a beneficial
      effect on catalytic efficiency. Comparison of the specificity changes obtained
      for the various substrates suggested that the maximization of the van der Waals
      contacts between substrate and PR is the major determinant of specificity: the
      same effect is crucial for inhibitor potency. The natural nucleocapsid/p1 and
      p1/p6 sites do not appear to be optimized for rapid hydrolysis. Hence, mutation
      of these rate limiting cleavage sites can partly compensate for the reduced
      catalytic activity of drug resistant mutant HIV-1 proteinases.

PMID- 12180989
TI  - Unfolding and aggregation during the thermal denaturation of streptokinase.
AB  - The thermal denaturation of streptokinase from Streptococcus equisimilis (SK)
      together with that of a set of fragments encompassing each of its three domains
      has been investigated using differential scanning calorimetry (DSC). Analysis of
      the effects of pH, sample concentration and heating rates on the DSC thermograms
      has allowed us to find conditions where thermal unfolding occurs unequivocally
      under equilibrium. Under these conditions, pH 7.0 and a sample concentration of
      less than approximately 1.5 mg x mL(-1), or pH 8.0, the heat capacity curves of
      intact SK can be quantitatively described by three independent two-state
      transitions, each of which compares well with the two-state transition observed
      for the corresponding isolated SK domain. The results indicate that each
      structural domain of SK behaves as a single cooperative unfolding unit under
      equilibrium conditions. At pH 7.0 and high sample concentration, or at pH 6.0 at
      any concentration investigated, the thermal unfolding of domain A was accompanied
      by the time-dependent formation of aggregates of SK. This produces a severe
      deformation of the DSC curves, which become concentration dependent and
      kinetically controlled, and thus precludes their proper analysis by standard
      deconvolution methods. A simple model involving time-dependent, high-order
      aggregation may account for the observed effects. Limited-proteolysis experiments
      suggest that in the aggregates the N-terminal segment 1-63 and the whole of SK
      domain C are at least partially structured, while domain B is highly
      unstructured. Unfolding of domain A, under conditions where the N-terminal
      segment 1-63 has a high propensity for beta sheet structure and a partially
      formed hydrophobic core, gives rise to rapid aggregation. It is likely that this
      region is able to act as a nucleus for the aggregation of the full-length
      protein.

PMID- 12180991
TI  - Enhancement of oxidative stress-induced apoptosis by Hsp105alpha in mouse
      embryonal F9 cells.
AB  - Hsp105alpha is one of the major mammalian heat shock proteins that belongs to the
      HSP105/110 family, and is expressed at especially high levels in the brain as
      compared with other tissues in mammals. Previously, we showed that Hsp105alpha
      prevents stress-induced apoptosis in neuronal PC12 cells, and is a novel anti
      apoptotic neuroprotective factor in the mammalian brain. On the other hand, we
      have also demonstrated that Hsp105alpha is expressed transiently at high levels
      during mouse embryogenesis and is found not only in various tissues but also in
      apoptotic cells. In the present study, to elucidate the role of Hsp105alpha
      during mouse embryogenesis, we established mouse embryonal F9 cell lines that
      constitutively over-express Hsp105alpha. Over-expression of Hsp105alpha enhanced
      hydrogen peroxide-induced apoptosis by enhancing the activation of caspase-3,
      poly(ADP-ribose)polymerase cleavage, cytochrome c release and activation of p38
      mitogen-activated protein kinase (p38). Furthermore, oxidative stress-induced
      apoptosis was suppressed by SB202190, a potent inhibitor of p38, in F9 cells.
      These findings indicated that the activation of p38 is an essential step for
      apoptosis in F9 cells and that Hsp105alpha enhances activation of p38, release of
      cytochrome c and caspase activation. Hsp105alpha may play important roles in
      organogenesis, during which marked apoptosis occurs, by enhancing apoptosis
      during mouse embryogenesis.

PMID- 12180990
TI  - Functional expression and mutational analysis of flavonol synthase from Citrus
      unshiu.
AB  - Flavonols are produced by the desaturation of flavanols catalyzed by flavonol
      synthase. The enzyme belongs to the class of intermolecular dioxygenases which
      depend on molecular oxygen and FeII/2-oxoglutarate for activity, and have been in
      focus of structural studies recently. Flavonol synthase cDNAs were cloned from
      six plant species, but none of the enzymes had been studied in detail. Therefore,
      a cDNA from Citrus unshiu (Satsuma mandarin) designated as flavonol synthase was
      expressed in Escherichia coli, and the purified recombinant enzyme was subjected
      to kinetic and mutational chacterizations. The integrity of the recombinant
      synthase was revealed by a molecular ion from MALDI-TOF mass spectrometry at m/z
      37888 +/- 40 (as compared to 37899 Da calculated for the translated polypeptide),
      and by partial N-terminal sequencing. Maximal flavonol synthase activity was
      observed in the range of pH 5-6 with dihydroquercetin as substrate and a
      temperature optimum at about 37 degrees C. Km values of 272, 11 and 36 micro m
      were determined for dihydroquercetin, FeII and 2-oxoglutarate, respectively, with
      a sixfold higher affinity to dihydrokaempferol (Km 45 micro m). Flavonol synthase
      polypeptides share an overall sequence similarity of 85% (47% identity), whereas
      only 30-60% similarity were apparent with other dioxygenases. Like the other
      dioxygenases of this class, Citrus flavonol synthase cDNA encodes eight strictly
      conserved amino-acid residues which include two histidines (His221, His277) and
      one acidic amino acid (Asp223) residue for FeII-coordination, an arginine
      (Arg287) proposed to bind 2-oxoglutarate, and four amino acids (Gly68, His75,
      Gly261, Pro207) with no obvious functionality. Replacements of Gly68 and Gly261
      by alanine reduced the catalytic activity by 95%, while the exchange of these Gly
      residues for proline completely abolished the enzyme activity. Alternatively, the
      substitution of Pro207 by glycine hardly affected the activity. The data suggest
      that Gly68 and Gly261, at least, are required for proper folding of the flavonol
      synthase polypeptide.

PMID- 12180992
TI  - Electrostatic role of aromatic ring stacking in the pH-sensitive modulation of a
      chymotrypsin-type serine protease, Achromobacter protease I.
AB  - Achromobacter protease I (API) has a unique region of aromatic ring stacking with
      Trp169-His210 in close proximity to the catalytic triad. This paper reveals the
      electrostatic role of aromatic stacking in the shift in optimum pH to the
      alkaline region, which is the highest pH range (8.5-10) among chymotrypsin-type
      serine proteases. The pH-activity profile of API showed a sigmoidal distribution
      that appears at pH 8-10, with a shoulder at pH 6-8. Variants with smaller amino
      acid residues substituted for Trp169 had lower pH optima on the acidic side by 0
      0.9 units. On the other hand, replacement of His210 by Ala or Ser lowered the
      acidic rim by 1.9 pH units, which is essentially identical to that of
      chymotrypsin and trypsin. Energy minimization for the mutant structures suggested
      that the side-chain of Trp169 stacked with His210 was responsible for isolation
      of the electrostatic interaction between His210 and the catalytic Asp113 from
      solvent. The aromatic stacking regulates the low activity at neutral pH and the
      high activity at alkaline pH due to the interference of the hydrogen bonded
      network in the catalytic triad residues.

PMID- 12180993
TI  - Amyloidogenic nature of spider silk.
AB  - In spiders soluble proteins are converted to form insoluble silk fibres, stronger
      than steel. The final fibre product has long been the subject of study; however,
      little is known about the conversion process in the silk-producing gland of the
      spider. Here we describe a study of the conversion of the soluble form of the
      major spider-silk protein, spidroin, directly extracted from the silk gland, to a
      beta-sheet enriched state using circular dichroism (CD) spectroscopy. Combined
      with electron microscopy (EM) data showing fibril formation in the beta-sheet
      rich region of the gland and amino-acid sequence analyses linking spidroin and
      amyloids, these results lead us to suggest that the refolding conversion is
      amyloid like. We also propose that spider silk could be a valuable model system
      for testing hypotheses concerning beta-sheet formation in other fibrilogenic
      systems, including amyloids.

PMID- 12180994
TI  - A sheep model for the study of focal epilepsy with concurrent intracranial EEG
      and functional MRI.
AB  - PURPOSE: We describe a sheep model of penicillin-induced seizure activity using
      electroencephalography (EEG) and functional MRI (fMRI). METHODS: Ten adult sheep
      were used. Spikes and seizures were generated by instillation of 8,000-10,000 IU
      of penicillin into the right prefrontal cortex via a specially designed port.
      Bilateral intracranial EEG was acquired by using carbon fiber electrodes. Animals
      had behavioral characterization of their seizures and were then anesthetized for
      fMRI studies. Functional MRI was performed at 1.5 and 3 Tesla by measuring blood
      oxygen level-dependent (BOLD) weighted signal intensity at different times during
      the evolution of seizures. RESULTS: Behavioral seizures were associated with
      electrographic seizures. Intracranial EEG obtained in the MR scanner was of high
      quality. Focal spiking and seizures were seen in all animals and developed 11.3
      +/- 11.2 s and 17.3 +/- 12.1 min after penicillin administration, respectively.
      An average of 13 +/- 4.8 seizures were seen per animal, each lasting 27.3 +/-
      12.3 s. Functional MR images with little parenchymal artefact were obtained.
      Regional BOLD signal-intensity changes were observed during seizures at the
      seizure focus and ipsilateral amygdala. CONCLUSIONS: We have developed an animal
      model of partial epilepsy in which seizures can be reliably elicited with
      concurrent fMRI and intracranial EEG. During unilateral electrographic seizures,
      focal BOLD signal changes occurred at the seizure focus and ipsilateral amygdala,
      suggesting the presence of a cortico-subcortical loop. This observation
      illustrates the potential of the model for understanding seizure generation,
      spread, and possibly the consequences of repeated seizures on the brain.

PMID- 12180995
TI  - Seizure suppression by adenosine-releasing cells is independent of seizure
      frequency.
AB  - PURPOSE: Intraventricular cellular delivery of adenosine was recently shown to be
      transiently efficient in the suppression of seizure activity in the rat kindling
      model of epilepsy. We tested whether the suppression of seizures by adenosine
      releasing grafts was independent of seizure frequency. METHODS: Adenosine
      releasing cells were encapsulated and grafted into the lateral brain ventricle of
      rats kindled in the hippocampus. During 4 weeks after grafting, electric test
      stimulations were delivered at a frequency of either once a week or 3 times per
      week. Seizure activity was evaluated by visual scoring of seizure severity and by
      the recording of EEGs. RESULTS: Adenosine released from encapsulated cells
      exerted potent antiepileptic activity for >/=2 weeks. One week after grafting,
      treated rats displayed a complete protection from clonic seizures, and a
      protection from focal seizures was observed in the majority of animals. Seizure
      suppression was accompanied by a reduction of afterdischarges in EEG recordings.
      The protective efficacy of the grafted cells was the same irrespective of whether
      electrical test stimulations were delivered 1 or 3 times per week. Rats receiving
      control grafts continued to display full clonic convulsions. CONCLUSIONS: This
      study demonstrated that the frequency of test stimulations did not influence the
      seizure-suppressive potential of adenosine-releasing grafts. Thus the local
      delivery of adenosine is likely to be effective in seizure control over a
      threefold range of seizure-discharge frequency.

PMID- 12180996
TI  - The role of alpha2-adrenoceptors in the modulatory effects of morphine on seizure
      susceptibility in mice.
AB  - PURPOSE: To evaluate the effect of the alpha2-adrenoceptor agonist clonidine and
      the antagonist yohimbine on the dual modulation of seizure susceptibility induced
      by morphine and the anticonvulsant effect of acute stress in mice. METHODS: The
      thresholds for the clonic seizures induced after intravenous administration of
      pentylenetetrazole (PTZ) or bicuculline were assessed in mice weighing 23-30 g.
      Acute stress was induced by restraining mice for 2 h in a restrainer. RESULTS:
      Morphine at lower doses (0.5, 1, and 3 mg/kg) increased and, at higher doses (15,
      30, and 75 mg/kg), decreased the seizure threshold. Pretreatment with clonidine
      (0.001-0.1 mg/kg) inhibited the anticonvulsant effect of morphine, while
      potentiating its proconvulsant effect. Conversely, yohimbine (0.5-2 mg/kg)
      potentiated the anticonvulsant effect of morphine but inhibited its proconvulsant
      effects. Acute stress induced an anticonvulsant effect that was reversible by
      naloxone (1 mg/kg) or clonidine (0.05-0.1 mg/kg) or a combination of their lower
      doses (0.3 and 0.01 mg/kg, respectively), while being potentiated by yohimbine (1
      mg/kg). CONCLUSIONS: alpha2-Adrenoceptors play a dual role in the anticonvulsant
      effects of morphine. The activation of these receptors also can decrease the
      anticonvulsant effect of acute restraint stress in mice.

PMID- 12180997
TI  - Amygdaloid kindling in glutamate transporter (GLAST) knockout mice.
AB  - PURPOSE: Glutamate is the predominant excitatory neurotransmitter in the
      mammalian central nervous system. We previously reported abnormal glutamate
      release during seizures after kindling. GLAST and GLT-1 are astrocytic glutamate
      transporters, highly concentrated in the cerebellum and the telencephalon,
      respectively. We have investigated whether stages of amygdala kindling in
      knockout (KO) mice deficient in GLAST are the same as those of wild mice.
      METHODS: Electrodes were implanted into the basolateral amygdala, bilaterally, in
      C57BL/6J mice and GLAST KO mice under anesthesia. Once-daily stimulation was
      applied on one side through these electrodes, and bilateral EEG recordings were
      obtained. RESULTS: The behavioral manifestations of kindling in mice were (a)
      arrest of behavior, (b) head nodding, (c) forelimb clonus, (d) bilateral forelimb
      clonus with rearing, (e) tonic generalized convulsion with elevation of tail and
      falling with generalized tonic convulsion (GTC). Results of kindling: (a) Mutant
      mice kindled more slowly than wild-type mice (more stimulations were required to
      reach each stage in mutants); (b) after kindling was completed, additional
      stimulations induced shorter afterdischarges (ADs) in mutants than in wild-type
      mice; (c) Interictal epileptic spikes were more frequent in the mutants than in
      the wild-type mice, both in the stimulated amygdala and in the contralateral
      amygdala. CONCLUSIONS: GLAST KO mice, which are missing one type of astrocytic
      glutamate transporter, demonstrate kindling of an epileptic focus. However, the
      kindling is significantly slower in the GLAST mutant than in wild-type mice.
      These findings suggest that glutamate transport by the astrocytic GLAST
      transporter may have a role in normal epileptogenesis.

PMID- 12180998
TI  - The effect on vision of associated treatments in patients taking vigabatrin:
      carbamazepine versus valproate.
AB  - PURPOSE: To evaluate the effect on visual function of a concomitant antiepileptic
      drug (AED) in patients treated with vigabatrin (VGB). METHODS: Sixty-four
      consecutive patients with a history of partial seizures currently treated with
      VGB with either carbamazepine (CBZ) or valproate (VPA) were examined with
      automated kinetic perimetry, static perimetry, electrooculogram (EOG), and
      electroretinogram (ERG). An original device based on kinetic perimetry was
      developed to quantify the area of perception for each isopter. RESULTS: Fifty-two
      patients were finally included. The results showed a significant difference in
      patients treated with VGB-VPA compared with patients treated with VGB-CBZ
      concerning the mean defect of static perimetry and the peripheral and
      midperipheral isopter (III 4e and III 1a Goldmann equivalent, respectively) in
      kinetic perimetry. EOG and ERG results did not differ significantly between the
      two groups. CONCLUSIONS: The visual impairment due to visual field constriction
      was more important in patients treated with VGB and VPA compared with patients
      treated with VGB and CBZ. The origin of this difference between the two
      associations could not be related to any particular retinal electrophysiologic
      abnormality.

PMID- 12180999
TI  - Lack of an effect of topiramate on lamotrigine serum concentrations.
AB  - PURPOSE: Pharmacokinetic interactions between the older antiepileptic drugs
      (AEDs) and topiramate (TPM) were assessed during the clinical development of this
      drug. Lamotrigine (LTG) has become established as an important new drug in
      treating a wide spectrum of seizure types, but there are no published data on
      whether LTG serum concentrations change when TPM is added to treatment. METHODS:
      Escalating doses of TPM were added to stable LTG treatment in 24 young patients
      (8-21 years) with epilepsy. Blood samples taken before the morning dose were
      collected for drug-concentration measurement in all patients before starting
      treatment with TPM and after stabilisation at each dose escalation. Several
      patients had been maintained on unchanged therapy with drug-concentration
      monitoring for many months before introducing TPM, and a sequence of baseline LTG
      serum concentrations were available on these patients. RESULTS: The mean of all
      baseline LTG concentrations for the group as a whole was 10.4 +/- 4.4 mg/L
      compared with 9.7 +/- 4.3 mg/L after addition of TPM. A comparison of last
      baseline LTG concentration with first test LTG concentration (i.e., after 2
      weeks' TPM treatment) gave mean values of 10.7 +/- 4.7 and 10.8 +/- 4.6 mg/L,
      respectively. The mean LTG concentration for patients while taking their highest
      TPM dose was 9.5 +/- 4.3 mg/L. The analysis-of-variance modeling for the effect
      of TPM on LTG concentration yielded a mean LTG concentration ratio (with TPM vs.
      without TPM) of 94.2%, with a 90% confidence interval of 89.5-99.1%. CONCLUSIONS:
      TPM did not cause a significant change in LTG serum concentration in this group
      of patients.

PMID- 12181000
TI  - Self-discontinuation of antiepileptic medication in pregnancy: detection by hair
      analysis.
AB  - PURPOSE: Concerns over teratogenicity of antiepileptic drugs (AEDs) during
      pregnancy must be balanced against the risks of seizures to the mother and
      developing fetus. Pharmacokinetic changes and vomiting may alter drug levels, but
      more important may be the patient's decision to stop medication before or during
      pregnancy. Compliance assessment traditionally relies either on self-reporting or
      on AED plasma level monitoring; neither provides reliable information on drug
      taking behaviour over an extended interval (e.g., before, during, and after
      pregnancy). METHODS: We have used hair analysis to assess AED-taking behavior in
      pregnant women compared with nonpregnant female controls. Twenty-six pregnant
      women [mean age, 27.5 +/- 6.7 (SD) years] and 13 nonpregnant female epilepsy
      outpatients (mean age, 31.9 +/- 8.3 years) were studied. Carbamazepine (CBZ) or
      lamotrigine (LTG) concentrations were measured in 1-cm hair segments, and the
      within-subject variance in segmental hair concentrations of these drugs was
      calculated for each group. The variances of each group were then compared by
      using a variance ratio test. RESULTS: The variance of AED concentration in hair
      differed significantly between the pregnant and nonpregnant groups [variance
      ratio, 1.59 (p < 0.01)]. Four (15%) of the 26 pregnant patients had little or no
      AED in their proximal hair segments compared with more distal segments,
      apparently having discontinued their medication during pregnancy. Only one of
      these later disclosed having stopped her medication. One pregnant woman whose
      hair profile was similar to controls died suddenly at 30 weeks of gestation.
      CONCLUSIONS: This study confirms the perception that pregnant women with epilepsy
      frequently stop or greatly reduce their prescribed medication, usually without
      reference or acknowledgement to their clinician.

PMID- 12181001
TI  - Epileptic seizures in Behcet disease.
AB  - PURPOSE: To outline the clinical characteristics of seizures in our large series
      of Behcet disease (BD) patients with neurologic involvement. METHODS: All files
      of 223 patients with neuro-BD were evaluated retrospectively, and the group with
      clearly documented seizures was included in the current study. Clinical
      characteristics, EEG, neuroimaging and cerebrospinal fluid findings were
      reevaluated, and the seizures were classified according to the new proposed
      criteria of the International League Against Epilepsy. On excluding the patients
      in whom the seizures were due to possible seizure-provoking factors, the seizures
      that appeared during a neurologic exacerbation were noted. RESULTS: Seizures were
      seen in 10 (4.48%) of 223 patients. There were one female and nine male patients.
      In five of the patients, seizures occurred during neurologic exacerbation.
      Therefore, the actual prevalence of seizures due to BD in our group is 2.2%. In
      the remaining five patients, the seizures were not related to neurologic BD
      attacks, but probably were due to some seizure-provoking factors. The
      predominating seizure type was generalized tonic-clonic convulsions accompanied
      by focal motor seizures. It is notable that four patients died 1-5 years after
      the onset of the seizures. CONCLUSIONS: Our study showed that seizures are rare
      in BD. As the seizures due to some interventions and drugs are as frequent as
      neuro-BD-related seizures, seizure-provoking factors must be considered before
      attributing them to the pathogenetic mechanism of BD. The occurrence of seizures
      seems to be associated with a high mortality rate.

PMID- 12181002
TI  - Optimizing parameters for terminating cortical afterdischarges with pulse
      stimulation.
AB  - PURPOSE: We previously reported that brief pulses of electrical stimulation
      (BPSs) can terminate afterdischarges (ADs) during cortical stimulation. We
      investigated conditions under which BPS is more likely to suppress ADs. METHODS:
      We analyzed parameters altering BPS effectiveness on 200 ADs in seven patients
      with implanted subdural electrodes. RESULTS: The odds of BPSs stopping ADs was
      8.6 times greater at primary sites (directly stimulated electrodes) than at
      secondary sites (adjacent electrodes) (p = 0.016). BPS applied within 4.5 s after
      onset of AD had 2 times greater odds of stopping ADs (p = 0.014). BPS applied
      when AD voltage was negative was 1.9 times more likely to stop ADs (p = 0.012).
      ADs with rhythmic pattern responded best (p < 0.0001). BPS stopped 100% of ADs
      not starting immediately after localization stimulus (LS) versus 29% of those
      starting immediately (p < 0.0001). CONCLUSIONS: BPS is more likely to terminate
      ADs at primary electrodes, if given early, if applied to the negative peak of the
      AD waveform, if AD has a rhythmic pattern, and if AD did not start immediately
      after LS.

PMID- 12181003
TI  - Heart rate changes and ECG abnormalities during epileptic seizures: prevalence
      and definition of an objective clinical sign.
AB  - PURPOSE: To determine the prevalence of heart rate changes and ECG abnormalities
      during epileptic seizures and to determine the timing of heart rate changes
      compared to the first electrographic and clinical signs. To assess the risk
      factors for the occurrence of ECG abnormalities. METHODS: We analyzed
      retrospectively 281 seizures in 81 patients with intractable epilepsy who had
      prolonged video-EEG and two-channel ECG. The nature and timing of heart rate
      changes compared to the electrographic and clinical seizure onset was determined.
      The ictal period (including one minute preictally and three minutes postictally)
      was analyzed for cardiac arrhythmias, conduction and repolarization
      abnormalities. Risk factors for cardiac abnormalities were investigated using
      parametric and non-parametric statistics. RESULTS: There was an increase in heart
      rate of at least 10 beats/minute in 73% of seizures (93% of patients) and this
      occurred most often around seizure onset. In 23% of seizures (49% of patients)
      the rate increase preceded both the electrographic and the clinical onset. ECG
      abnormalities were found in 26% of seizures (44% of patients). One patient had an
      asystole for 30 seconds. Long seizure duration increased the occurrence of ECG
      abnormalities. No other risk factor was found. CONCLUSIONS: Heart rate changes
      occur frequently and occur around the time or even before the earliest
      electrographic or clinical change. The change can clarify the timing of seizure
      onset and the specific rate pattern may be useful for seizure diagnosis and for
      automatic seizure detection. ECG abnormalities occur often and repeatedly in
      several seizures of the same patient.

PMID- 12181004
TI  - Memory lateralization in medial temporal lobe epilepsy assessed by functional
      MRI.
AB  - PURPOSE: To determine the utility of functional magnetic resonance imaging (fMRI)
      in preoperative lateralization of memory function in patients with medial
      temporal lobe epilepsy (MTLE). METHODS: Nine patients with MTLE underwent
      standard preoperative assessment including video-EEG and intracarotid amytal
      testing (IAT). fMRI was performed while subjects encoded four types of stimuli
      (patterns, faces, scenes, and words). Activation maps were created for each
      subject representing areas more active for novel than for repeated stimuli.
      Regions of interest were drawn around the MTL in individual subjects,
      suprathreshold voxels were counted, and an asymmetry index was calculated.
      RESULTS: In eight of nine subjects, lateralization of memory encoding by fMRI was
      concordant with that obtained from the IAT. Group-level analysis demonstrated
      greater activation in the MTL contralateral to the seizure focus such that in the
      left MTLE group, verbal encoding engaged the right MTL, whereas in the right MTLE
      group, nonverbal encoding engaged the left MTL. CONCLUSIONS: fMRI is a valid tool
      for assessing of memory lateralization in patients with MTLE and may therefore
      allow noninvasive preoperative evaluation of memory lateralization. FMRI revealed
      that memory encoding may be reorganized to the contralateral MTL in patients with
      MTLE.

PMID- 12181005
TI  - Use of intraoperative magnetic resonance imaging in tailored temporal lobe
      surgeries for epilepsy.
AB  - PURPOSE: We investigated whether intraoperative magnetic resonance imaging (MRI)
      was able to assess immediately the extent of a tailored temporal lobe resection
      for epilepsy in comparison to delayed postoperative MRI. The recently proposed
      concept of an individually tailored procedure, preserving tissue not involved in
      seizures, leads to a variety of differently shaped resections. METHODS: For
      intraoperative imaging we used a Magnetom Open 0.2 Tesla scanner. Fifty-eight
      patients undergoing temporal lobe resections for pharmacoresistant epilepsy were
      investigated. Half of these were nonlesional. All patients had delayed
      postoperative follow-up scans, which were compared with the intraoperative,
      postresection images. RESULTS: In 49 (84%) of 58 cases, intraoperative MRI
      depicted the resection cavity identical to delayed postoperative studies.
      Complete resection of the visible lesion was primarily proved in 23 of the 29
      cases. In two patients with lesions and in one nonlesional case, the resection
      was extended after intraoperative imaging, thus increasing the rate of total
      resections in gliomas from 73 to 87%. In four patients, an extension into
      eloquent areas did not allow complete removal. In the nonlesional cases (n = 29),
      the extent of tailored temporal resections also could be exactly documented
      intraoperatively. CONCLUSIONS: Intraoperative MRI allowed a reliable evaluation
      of the localization and extent of resection in epilepsy surgery within the
      operative procedure. Furthermore, it provided the possibility of an image-based
      correction of an initially incomplete resection, particularly in lesional cases.
      In the majority of patients, the intraoperative images would have been able to
      replace delayed postoperative MRI. However, in 16%, there were postoperative
      changes in the resection volume.

PMID- 12181006
TI  - Frequency and significance of acute postoperative seizures following epilepsy
      surgery in children and adolescents.
AB  - PURPOSE: To determine the frequency and prognostic features of acute
      postoperative seizures (APOSs), within the first postoperative week, in a group
      of children undergoing surgery for the treatment of medically refractory
      epilepsy. METHODS: Patients younger than 18 years who underwent surgery for the
      relief of medically intractable epilepsy at the Mayo Clinic between 1985 and 1998
      with a minimum of 12 months of follow-up were eligible. A retrospective chart
      review was conducted to abstract information regarding demographics, epilepsy
      history, and preoperative, intraoperative, and postoperative risk factors, APOSs,
      and outcome. A multivariate analysis was conducted to control for confounding
      variables. RESULTS: The study group was composed of 148 patients (mean age at
      surgery, 13 years; range, 5 months to 18 years). Twenty-five percent of patients
      experienced APOSs. Risk factors associated with a statistically significant (p <
      0.05) greater likelihood of experiencing APOS were non-complex partial seizure
      type, extratemporal surgery, postoperative fever, non-temporal lobe epilepsy, and
      postoperative interictal epileptiform activity. At last follow-up, patients who
      did not experience APOSs had a significantly greater chance of being seizure free
      (80 vs. 51%; p < 0.001). With a multivariate analysis, APOS was found to be an
      independent predictor of outcome. CONCLUSIONS: This study indicates that APOSs
      are predictive of a less favorable outcome in the pediatric postsurgical patient;
      however, 51% remained seizure free at last follow-up. Finally, the effects of
      APOSs on outcome were shown to be stable over a 12-month follow-up period.

PMID- 12181007
TI  - Hypomotor seizures in infants and children.
AB  - PURPOSE: Hypomotor seizures (characterized by diminished behavioral activity with
      indeterminate level of consciousness) have been identified as an important
      seizure type in infants. Our goal was to investigate further the clinical and EEG
      features of hypomotor seizures. METHODS: We retrospectively reviewed 110
      hypomotor seizures from 34 patients recorded with video-EEG. RESULTS: Twenty
      seven (79%) patients were younger than 48 months, and seven (21%) were aged 4 to
      15 years. Seventy-one (64%) seizures had regional or lateralized EEG onset,
      arising predominantly from temporal or parietal lobe regions. The other 39 (35%)
      seizures had generalized onset, usually with abrupt onset of diffuse rhythmic
      high-amplitude theta activity or diffuse electrodecrement and only rarely (two
      patients) with slow spike-wave complexes or 3-Hz spike-wave complexes. Hypomotor
      seizures with generalized EEG onset were significantly shorter than those with
      regional or lateralized onset (p = 0.01, GEE model). Unsustained head or eye
      movements and subtle mouth automatisms were commonly seen in hypomotor seizures
      with either focal or generalized onset. Seventeen percent of hypomotor seizures
      with focal onset evolved to include version of head and eyes or jerking of one
      arm, whereas 2% of generalized hypomotor seizures evolved to a cluster of spasms.
      CONCLUSIONS: Hypomotor seizures may be either focal or generalized. Regional EEG
      onsets were most often temporal or parietal, suggesting that focal hypomotor
      seizures may be a bland form of "complex partial" seizures with no or minimal
      automatisms, seen predominantly in infants. Generalized hypomotor seizures were
      rarely associated with an ictal pattern of generalized spike-wave complexes,
      suggesting a different mechanism from absence seizures seen later in life.

PMID- 12181009
TI  - Long-term psychosocial outcomes of anterior temporal lobectomy.
AB  - PURPOSE: To examine the long-term psychosocial outcomes of a consecutive series
      of patients who underwent anterior temporal lobectomy (ATL) compared with
      medically managed patients. This study focused primarily on actual long-term
      changes (mean, 5 years) in life performance. There are relatively few long-term
      controlled studies of actual lifetime performance changes. METHODS: The sample
      consisted of 61 adults who underwent ATL and 23 individuals who were evaluated
      for surgery but did not proceed to surgery and continued to receive medical
      management. Participants were interviewed 2-9 years after surgery. A structured
      clinical interview and review of medical records was conducted to obtain
      information regarding seizure frequency and psychosocial status, focusing on
      employment, education, driving status, financial assistance, and independent
      living. In addition, two questions regarding quality of life were included.
      Seizure frequency was evaluated for the year before the interview. RESULTS:
      Significant differences in psychosocial outcome were found between the surgery
      group and medical management group. Favorable psychosocial outcomes were more
      common among those who had surgery (46 vs. 4%). Results indicated that 68% of the
      surgery group exhibited improved psychosocial status compared with 5% of the
      medical management group. Individuals who had surgery were more likely to be
      driving, working full-time, living independently, and being financially
      independent. Remaining seizure free was not a prerequisite for improvements in
      psychosocial outcomes. CONCLUSIONS: Compared with medical management, surgery has
      a significant positive impact on psychosocial outcomes in terms of employment,
      independent living, driving, and financial independence. Additionally, a person
      does not necessarily have to be seizure free to achieve positive changes in
      psychosocial outcomes.

PMID- 12181008
TI  - Dream recall frequency in epilepsy patients with partial and generalized
      seizures: a dream diary study.
AB  - PURPOSE: The frequency of dream recall (DR) in patients with brain diseases has
      proved to be indicative of the relation between sleep disturbances and the
      functioning of cognitive processes during sleep. In this study we attempted to
      ascertain whether DR frequency in patients with complex partial seizures (CPSs)
      is higher than that in those with generalized seizures. METHODS: DR frequency was
      assessed by means of a 60-day dream diary in patients with CPSs, whose epileptic
      focus was in the right (n = 12) or left temporal lobe (n = 28), and with
      idiopathic generalized seizures (n = 21). The patients enrolled in the study were
      not impaired in global cognitive and memory functioning. RESULTS: The ability to
      recall dreams was established in nearly all patients with either CPSs or
      generalized seizures. DR frequency resulted significantly higher (about twice) in
      patients with CPSs, regardless of (a) the side of the epileptic focus, (b) the
      presence of a cerebral lesion detectable on a computed tomography (CT) scan, or
      (c) the occurrence of seizures in the previous day. CONCLUSIONS: These findings
      indicate that overall, DR occurs in medicated epilepsy patients with CPSs more
      frequently than reported in previous studies. The high DR frequency observed in
      these patients, regardless of the side of the epileptic focus, is in agreement
      with the assumption that tempoparietal areas of both hemispheres are involved in
      the production and recall of the dream experience.

PMID- 12181010
TI  - Help-seeking patterns for children with epilepsy in rural India: implications for
      service delivery.
AB  - PURPOSE: Most people in the world with epilepsy are untreated with antiepileptic
      drugs (AEDs). In some developing countries, this is because treatment facilities
      are unavailable or difficult to access. It has even been suggested that
      indigenous health systems threaten the prospect of the global control of epilepsy
      with AEDs. We have investigated patterns and costs of help seeking for children
      with epilepsy in a region of rural India where only 12% of children with epilepsy
      were in treatment. Our objective was to find out (a) whom families had consulted;
      (b) if nonconsulting families differed in demographic or child medical factors;
      (c) if indigenous treatment was taken, exclusive of allopathic treatment; and (d)
      the direct and indirect cost of various providers. METHODS: We conducted a cross
      sectional interview study in a community-based program for childhood epilepsy in
      rural West Bengal, India. We interviewed parents of 85 children aged 2 to 18
      years with untreated epilepsy who had entered a clinical trial of AEDs during
      1995 through 1996. RESULTS: Eighty percent of families had sought some help in
      the past: 62% with an allopathic practitioner, 44% with traditional
      practitioners. Primary health centres (PHCs) and quacks were not popular. Twenty
      four percent of families never sought help of any kind, and this was unassociated
      with sex, income, maternal literacy, or medical variables. There was evidence of
      both exclusivity and pluralism: 42% of families first consulting allopathic
      practitioners also visited traditional practitioners, whereas 30% of families
      first consulting traditional practitioners also went to allopathic practitioners.
      One visit to a physician cost a median of 9-13% of monthly income and 5-12 person
      hours; the cost of visiting indigenous providers was negligible. CONCLUSIONS:
      Most families sought some form of help and were motivated to spend large amounts
      of money and time for allopathic treatments from qualified practitioners. The
      typical cost of allopathic treatment was unsustainable in the long term. Medical
      pluralism is common and does not adversely influence use of allopathic treatment.
      The phenomenon of nonconsulting merits further study. Traditional practitioners
      play a complementary role and might become involved in community treatment
      programs. Low-cost, local treatment is essential to the public health control of
      epilepsy.

PMID- 12181011
TI  - Epilepsy in The Alienist and Neurologist, 1880-1920.
AB  - PURPOSE: To study the history of epilepsy from 1880 to 1920. METHODS: We reviewed
      all 40 volumes of The Alienist and Neurologist and identified articles concerning
      primarily epilepsy. We analyzed three of these articles in greater detail.
      RESULTS: The Alienist and Neurologist published "Original
      Contributions,""Selections," (abstracts from other journals written by the
      editorial board), "Editorials," and (book) "Reviews." Of 258 epilepsy articles,
      there were 40 Original Contributions, 164 Selections, 39 Editorials, and 15
      Reviews. These articles included 71 on therapy (41 medication, 13 surgery, and 17
      other therapies); 66 general discussions; 46 on etiology or symptoms; 34 case
      studies; 28 social/legal articles; and 13 autopsy or pathology articles.
      CONCLUSIONS: Analysis of The Alienist and Neurologist provides a unique and
      valuable perspective on the clinical practice and academic world of epileptology
      during the decades around the turn of the twentieth century.

PMID- 12181012
TI  - Increased plasma levels of pro- and anti-inflammatory cytokines in patients with
      febrile seizures.
AB  - PURPOSE: Pro- and antiinflammatory cytokines regulate the febrile response during
      infection. Febrile seizures (FSs) conversely are associated with rapid onset of
      high fever. Activation of the cytokine network has been shown in previous studies
      of FSs and cytokines. In this study, the association between cytokines and FSs
      was further investigated. METHODS: Interleukin-1beta (IL-1beta), interleukin-1
      receptor antagonist (IL-1RA), interleukin-6 (IL-6), interleukin-10, and tumor
      necrosis factor-alpha plasma levels were measured with enzyme-linked
      immunosorbent assay in 55 children with FSs and in 20 age-matched febrile
      controls immediately on arrival at the hospital. Cerebrospinal fluid cytokine
      levels also were measured in 16 FS children. RESULTS: The plasma IL-1RA/IL-1beta
      ratio (mean, 2,133 vs. 119; median, 790 vs. 105; p < 0.0001) and plasma IL-6
      (mean, 41.7 pg/ml vs. 16.1 pg/ml; median, 19.6 pg/ml vs. 10.5 pg/ml; p = 0.005)
      were significantly higher in FS patients compared with control children. Logistic
      regression analysis was used to find the most significant predisposing factors
      for FSs. In this analysis, the high plasma IL-1RA/IL-1beta ratio was the most
      significant factor connected to FSs (OR, 41.5; 95% CI, 4.9-352.8), but high
      plasma IL-6 also was significantly associated with FSs (OR, 5.3; 95% CI, 1.4
      20.3). CONCLUSIONS: Present results support the hypothesis that the cytokine
      network is activated and could have a role in the pathogenesis of FS.

PMID- 12181013
TI  - Benefit of simultaneous recording of EEG and MEG in dipole localization.
AB  - PURPOSE: In this study, we tried to show that EEG and magnetoencephalography
      (MEG) are clinically complementary to each other and that a combination of both
      technologies is useful for the precise diagnosis of epileptic focus. METHODS: We
      recorded EEGs and MEGs simultaneously and analyzed dipoles in seven patients with
      intractable localization-related epilepsy. MEG dipoles were analyzed by using a
      BTI Magnes 148-channel magnetometer. EEG dipoles were analyzed by using a
      realistically shaped four-layered head model (scalp-skull-fluid-brain) built from
      2.0-mm slice magnetic resonance imaging (MRI) images. RESULTS: (a) In two of
      seven patients, MEG could not detect any epileptiform discharges, whereas EEG
      showed clear spikes. However, dipoles estimated from the MEG data corresponding
      to the early phase of EEG spikes clustered at a location close to that of the EEG
      detected dipole. (b) In two of seven patients, EEG showed only intermittent high
      voltage slow waves (HVSs) without definite spikes. However, MEG showed clear
      epileptiform discharges preceding these EEG-detected HVSs. Dipoles estimated for
      these EEG-detected HVSs were located at a location close to that of the MEG
      detected dipoles. (c) Based on the agreement of the results of these two
      techniques, surgical resection was performed in one patient with good results.
      CONCLUSIONS: Dipole modeling of epileptiform activity by MEG and EEG sometimes
      provides information not obtainable with either modality used alone.

PMID- 12181014
TI  - Is there an association between maternal carbamazepine use during pregnancy and
      eye malformations in the child?
AB  - PURPOSE: To check for an association between carbamazepine (CBZ) use by the
      mother during pregnancy and congenital eye malformations (i.e., anophthalmia,
      microphthalmia, and coloboma) in the child, as suggested by Sutcliffe et al.
      (1998), who reported four cases. METHODS: We checked all the cases with these eye
      malformations for CBZ use by the mother in the EUROCAT Northern Netherlands
      dataset, which registers infants with congenital malformations and records
      possible teratogenic exposures (including medication taken by the mother). We
      also reviewed 13 studies in the literature. RESULTS: The EUROCAT dataset recorded
      77 cases of anophthalmia, microphthalmia, or coloboma, but none with prenatal
      exposure to CBZ. Prenatal CBZ exposure was recorded in seven other cases without
      congenital eye malformation. Large studies in the literature on the teratogenic
      effects of CBZ (and other antiepileptic drugs), including data from the MADRE
      database, revealed no association between these congenital eye malformations and
      prenatal CBZ exposure. One case reported bilateral anophthalmia and other
      congenital anomalies after prenatal exposure to CBZ in combination with
      vigabatrin and dexamethasone. CONCLUSIONS: Our data do not support Sutcliffe's
      suggestion that prenatal CBZ exposure may result in congenital eye malformations.
      However, despite the large population represented, both the low birth prevalence
      of these congenital eye malformations and the low prevalence of CBZ exposure
      during pregnancy make it difficult to exclude an increased relative risk. The
      many large prospective and retrospective studies in the literature seem to agree
      with our findings, although there is still uncertainty about the teratogenic
      effect of CBZ in polytherapy.

PMID- 12181015
TI  - Focal cooling suppresses spontaneous epileptiform activity without changing the
      cortical motor threshold.
AB  - PURPOSE: Focal cerebral cooling has been shown to reduce epileptiform activity in
      animals. There are, however, few reports of this phenomenon in humans. METHODS:
      Electrocorticography was performed before resection of a right frontal tumor in a
      patient with partial seizures. Cold saline was applied to the interictal spike
      focus, and its effect on the epileptiform discharges was observed. RESULTS:
      Application of cold saline to the spike focus resulted in a transient, complete
      cessation of spiking. This effect was reproduced with a second application of
      cold saline. The motor threshold for electrical stimulation remained unchanged
      during the application of saline. CONCLUSIONS: In this patient with tumor-related
      epilepsy, focal cooling of the cortex reproducibly abolished interictal
      epileptiform discharges without changing the motor threshold to electrical
      stimulation.

PMID- 12181016
TI  - Partial status epilepticus in benign childhood epilepsy with centrotemporal
      spikes: are independent right and left seizures a risk factor?
AB  - PURPOSE: To describe an association between continuous simple partial seizures
      and independent right and left partial seizures in children with benign childhood
      epilepsy with centrotemporal spikes (BCECTS). METHODS: Three children with BCECTS
      and episodes of continuous simple partial seizures are described. RESULTS: All
      three children had a history of typical rolandic seizures occurring on the right
      and left sides of the body on different occasions. CONCLUSIONS: The occurrence of
      independent right and left rolandic seizures in children with BCECTS may be a
      predisposing factor for the development of partial status epilepticus.

PMID- 12181017
TI  - EEG features of glut-1 deficiency syndrome.
AB  - PURPOSE: Glut-1 deficiency syndrome (Glut-1 DS) is caused by the deficiency of
      the major glucose transporter in cerebral microvessels. METHODS: We performed pre
      and postprandial EEG recordings in two unrelated children with Glut-1 DS with
      developmental delay and seizures predominantly in the morning before breakfast.
      RESULTS: Extensive epileptiform discharges observed in the fasting state were
      improved markedly by food intake, as documented in EEG recordings 1 and 2 h after
      a meal. The ratio of cerebrospinal fluid glucose to blood glucose was decreased
      in both children. Glut-1 deficiency was confirmed by biochemical and molecular
      genetic investigations. CONCLUSIONS: Pre- and postprandial EEG recordings offer a
      simple screening test for Glut-1 DS.

PMID- 12181018
TI  - Reflex seizures induced by defecation, with an ictal EEG focus in the left
      frontotemporal region.
AB  - We report a 9-year-old boy with seizures induced by defecation. The episodes
      occurred 1-2 min after passing a bowel action and consisted of initial staring,
      gagging, and drooling followed by a secondarily generalized tonic-clonic seizure.
      The interictal EEGs were normal, but an ictal EEG with concurrent video
      monitoring demonstrated a polyspike wave discharge in the left frontotemporal
      region. There was no evidence of syncope, and the seizures did not occur while
      straining to empty his bowels or immediately on standing afterward. His magnetic
      resonance imaging scan was normal. This is the first reported case in which ictal
      EEG monitoring has demonstrated reflex seizures induced by defecation.

PMID- 12181019
TI  - Kozhevnikov-Rasmussen syndrome and the new proposal on classification.

PMID- 12181021
TI  - The future for clinical scientists in laboratory medicine.
AB  - Clinical science in the UK has been presented with a range of opportunities and
      new initiatives in recent years. This review summarizes the contribution of
      clinical scientists to the changing face of laboratory medicine, and describes
      some recent UK Government initiatives to modernize the scientific service and
      develop the people who work in it. Recent changes in the regulation of
      professional practice and the need for maintenance of professional competence are
      also discussed.

PMID- 12181022
TI  - The erythrocyte adhesiveness/aggregation test for the detection of an acute phase
      response and for the assessment of its intensity.
AB  - We have developed a simple slide test and image analysis to reveal the state of
      erythrocyte adhesiveness/aggregation in the peripheral blood of patients with
      various degrees of the humoral acute phase response. The significant correlation
      between the results of the erythrocyte adhesiveness/aggregation test (EAAT), the
      erythrocyte sedimentation rate and fibrinogen concentration support the notion
      that it is possible to use the EAAT as a marker for the intensity of the acute
      phase response. Within a group of 860 individuals, we were able to differentiate
      effectively between groups of patients with a different intensity of humoral
      acute phase response. The present study confirms previous observations that
      support the applicability of the EAAT to routine clinical practice.

PMID- 12181023
TI  - Treatment of myelodysplasia with oral cyclosporin.
AB  - Recent studies have shown a good response to immunosuppressive treatment with
      cyclosporin A (CSA) in patients with the myelodysplastic syndrome (MDS). We have
      treated six transfusion-dependent MDS patients with CSA for a minimum of 3
      months. None of these patients showed a significant response, while the drug was
      withdrawn in 3/6 patients because of intolerable side-effects. Two reasons for
      the failure of this treatment in our patients can be advanced. Firstly, the
      hypoplastic variant of MDS predominated in previous studies in contrast to ours.
      Secondly, the concomitant use of other immunosuppressive agents in previous
      studies might have enhanced the effect of CSA. We suggest further therapeutic
      trials of CSA in MDS, selecting patients on the basis of in vitro studies that
      predict an immunological basis for their disease, to assess its efficacy in
      prolonging survival.

PMID- 12181024
TI  - HLA class I and class II antigens associated with multiple myeloma in southern
      Africa.
AB  - While the exact aetiology of myeloma is unknown, genetic factors feature among
      the potential risk factors. The HLA phenotypes in African blacks with myeloma
      (the commonest haematopoietic malignancy in this group) have not been
      characterized. The purpose of this study was to determine the HLA class I and
      class II phenotypes of patients with multiple myeloma and to compare the findings
      to an ethnically matched control group of 100 individuals. Analysis of the HLA
      class I and class II phenotypes in 62 myeloma patients revealed: (i) a
      corresponding statistically significant association with HLA B18 [odds ratio (OR)
      6.3; 95% confidence interval (CI) 1.013-39.727; P < 0.005]; (ii) no statistically
      significant association with HLA B13, Cw2, Cw6 or the DR and DQ antigens; and
      (iii) a statistically significant negative (protective) association with HLA Cw7
      (OR 0.4; 95% CI 0.21-0.87; P < 0.005). This study suggests that although genetic
      factors may play a role in the multifactorial aetiology of multiple myeloma, with
      the exception of HLA B18, there is no specific association between HLA types and
      multiple myeloma in South African blacks.

PMID- 12181025
TI  - Role of bone marrow examination in staging Hodgkin's disease: experience in
      Mexico.
AB  - We assessed the value of bone marrow biopsy prospectively in a group of 91
      individuals with Hodgkin's disease. The median age of our population was 29 years
      (range 4-87 years); 59 were males. Most patients (45%) had nodular sclerosing
      disease and most patients (44%) were in pathological stage II at diagnosis. The
      bone marrow biopsy showed infiltration by Hodgkin's disease in only three
      individuals (3.3%); two of these patients displayed constitutional symptoms and
      had been assigned to stage III before the biopsy. In one case, bone marrow biopsy
      was the diagnostic procedure, which was performed as part of the investigation of
      fever of unknown origin. Follow-up periods ranged between 1 and 117 months
      (median 16 months). All patients achieved complete remission, seven patients
      relapsed and four were given autologous stem cell transplants. The median
      survival of the whole group was 117 months, while the 3500-day survival was 76%.
      As bone marrow biopsy was the diagnostic procedure in one case, bone marrow
      biopsy was a useful staging procedure in only 2.2% of patients (two out of 90
      patients). We suggest that bone marrow biopsy should be only be performed as a
      staging procedure in a selected subset of patients with Hodgkin's disease
      (clinical stage III, B symptoms, etc.).

PMID- 12181026
TI  - The PFA-100: a potential rapid screening tool for the assessment of platelet
      dysfunction.
AB  - The PFA-100 is a device that simulates high shear dependent platelet function in
      vitro and thus is particularly useful for screening for von Willebrand's disease
      (VWD). The aim of this study was to assess the overall potential of the PFA-100
      as a primary clinical screening tool using the wide spectrum of clinical samples
      assessed for platelet function within our institution. The PFA-100 test was
      performed using both collagen/ADP (CADP) and collagen/epinephrine (CEPI)
      cartridges on samples from 337 patients with a wide variety of haemostatic
      defects. One hundred and eighty-two patients were defined as having normal
      platelet function based on classical laboratory tests and von Willebrand factor
      levels. The overall clinical sensitivity of the PFA-100 for platelet
      abnormalities (including VWD) was 81% for CADP and 86% for CEPI. The overall
      specificity was found to be 82% for CADP and 80% for CEPI. When utilizing both
      cartridges in combination (with both results either higher or lower than the
      upper cutoff of the normal ranges), the overall false positive and false negative
      rates were 12% and 6%, respectively. The PFA-100 proved to be sensitive in
      detecting classical defects by giving prolonged closure times in samples from
      patients with major platelet function defects (e.g. von Willebrand's disease,
      Glanzmann's thrombasthenia and Bernard Soulier syndrome). However, there were a
      small number of false negative results (6%) obtained with various milder platelet
      defects (e.g. Hermansky Pudlak syndrome, storage pool and release defects, type I
      VWD and macrothrombocytopenia). The PFA-100 test provides a useful rapid
      screening tool and should increase the efficiency and reduce the cost of the
      routine diagnosis of platelet dysfunction.

PMID- 12181028
TI  - Portal or hepatic vein thrombosis as the first presentation of a
      myeloproliferative disorder in patients with normal peripheral blood counts.
AB  - Myeloproliferative disorders (MPD) are associated with an increased risk of
      thrombotic complications. We describe three patients with portal or hepatic vein
      thrombosis and normal peripheral blood counts who had MPD on bone marrow
      morphology and growth factor-independent megakaryocyte or erythroid colony growth
      in vitro. The peripheral blood counts have become abnormal subsequently in two
      patients. Patients presenting with unexplained portal or hepatic vein thrombosis
      should be investigated systematically for the presence of a MPD, which may not be
      apparent using conventional diagnostic criteria.

PMID- 12181027
TI  - Human factor VII deficiency caused by S339C mutation located adjacent to the
      specificity pocket of the catalytic domain.
AB  - This report documents our identification of a novel factor VII (FVII) gene
      mutation in a Japanese boy with FVII deficiency. The proband's FVII activity was
      34% and his FVII antigen level was 40% of normal controls. DNA sequence analysis
      of the proband's FVII gene identified a C to G point mutation at nucleotide
      position 10 933 in exon 8, which results in the substitution of Cys (TGC) for
      Ser339 (TCC). Hinf I digestion results indicate the proband and his mother were
      heterozygous for the mutation. Both wild-type and mutant FVIIs were transiently
      expressed in COS-1 cells. FVII levels measured in the culture medium of FVII
      Ser339Cys mutants were markedly reduced as compared to those of cells with FVII
      wild-type. The amount of intracellular FVII in FVII Ser339Cys mutants was 80% of
      that in wild-type. In the wild-type FVII, Ser339 is juxtaposed to Asp338, which
      is positioned at the bottom of the substrate-binding pocket in the protease
      domain and located adjacent to FVII Cys340, that forms a disulphide bond with
      Cys368. We suspect that the creation of a novel unpaired cysteine through this
      mutation leads to abnormal disulphide bonding during protein folding, thereby
      reducing the secretion of FVII.

PMID- 12181029
TI  - Coagulation abnormalities associated with extensive venous malformations of the
      limbs: differentiation from Kasabach-Merritt syndrome.
AB  - Confusion in the nomenclature of vascular malformations has been a major obstacle
      to the understanding of these conditions, so that misdiagnosis and treatment
      inconsistencies are common. Coagulation abnormalities occurring in combination
      with venous malformations (VM) have been misdiagnosed as Kasabach-Merritt
      syndrome (KMS), despite marked differences in clinical features, pathology and
      treatment. A homogenous group of 24 patients with diffuse limb VM was entered
      into a retrospective chart review study. The VM affected an upper limb in 12
      patients, a lower limb in 10 and both in two. Localized intravascular coagulation
      (LIC) was characterized by a decrease in fibrinogen (0.5-1 g/l), an increase in d
      dimers (2-64 micro g/ml) and presence of soluble complex of fibrin (+ to +++).
      Platelet counts were normal or slightly decreased. Higher VM severity scores were
      associated with more severe LIC. A number of events such as sclerotherapy,
      surgery, bone fracture, prolonged immobilization and pregnancy or menstruation
      triggered conversion of the LIC to disseminated intravascular coagulation (DIC),
      with bleeding related to factor consumption and multiorgan failure related to
      disseminated microvascular thrombosis. Clinical symptoms associated with
      worsening of LIC were pain, thrombosis and bleeding at wound sites or during
      surgery. None of the patients had the large ecchymotic and inflammatory tumours
      seen in KMS. Graded permanent elastic compression with heparin therapy was the
      only effective treatment. In conclusion, VM-associated LIC is a distinctive
      lifelong coagulopathy that must be differentiated from KMS, which is
      characterized by platelet trapping within a vascular tumour of infancy. The
      treatment of the two conditions is very different.

PMID- 12181030
TI  - Patient self-management of oral anticoagulation.
AB  - Patient self-management of oral anticoagulation is now widely practised in
      Germany and the USA. There are three different home-testing monitors available in
      the UK which are all reliable in terms of accuracy and reproducibility of
      results. Selected patients can be trained to perform their own International
      Normalized Ratio (INR) testing and dosing, with outcomes as good if not better
      than those from specialized anticoagulant clinics. Consensus on the frequency of
      testing and what quality control should be deployed is lacking. The cost
      effectiveness in the UK is unproven.

PMID- 12181031
TI  - Systemic vasculitis complicating hairy cell leukaemia treatment with cladribine.
AB  - A single course of cladribine has been used commonly over the past decade to
      treat hairy cell leukaemia, with an impressive rate of complete remission and few
      serious adverse effects. Although vasculitis has been reported in the course of
      hairy cell leukaemia, it has only rarely been reported as the consequence of
      cladribine treatment. We describe a 73-year-old woman who developed serious
      systemic vasculitis with associated thrombocytopenia in the course of treatment
      with cladribine.

PMID- 12181032
TI  - Not all cases of idiopathic thrombocytopenic purpura [correction of pupura] are
      what they might first seem.
AB  - We present the case of a patient diagnosed as having presumed idiopathic
      thrombocytopenic purpura (ITP) who subsequently developed chronic myelomonocytic
      leukaemia (CMML) after an interval of 16 months. A variety of peripheral
      cytopenias are commonly seen in myelodysplastic disorders (MDS), and autoimmune
      phenomena, including secondary ITP, are well described, especially in cases of
      CMML. We would advocate evaluation for possible MDS/CMML by morphological
      examination of the peripheral blood/bone marrow in adult patients presenting with
      isolated thrombocytopenia, especially if there is subsequent development of
      additional peripheral cytopenias, monocytosis or hepatosplenomegaly.

PMID- 12181033
TI  - Patients entered into MRC AML trials are biologically representative of the
      totality of the disease in the UK.

PMID- 12181034
TI  - Giant cell arteritis detected by bone marrow trephine.

PMID- 12181035
TI  - Bladder chloroma complicating refractory anaemia with excess of blasts.

PMID- 12181036
TI  - Factor VII Deficiency.

PMID- 12181037
TI  - Shwachman-diamond syndrome.

PMID- 12181038
TI  - Chromatin modification, leukaemia and implications for therapy.

PMID- 12181039
TI  - Immunotherapy for post-transplant lymphoproliferative disease.

PMID- 12181040
TI  - A single high dose of idarubicin combined with high-dose ARA-C for treatment of
      first relapse in childhood 'high-risk' acute lymphoblastic leukaemia: a study of
      the AIEOP group.
AB  - The outcome of children with acute lymphoblastic leukaemia (ALL) and early
      relapse remains unsatisfactory. In January 1995, the AIEOP (Associazione Italiana
      di Oncologia ed Ematologia Pediatrica) group opened a trial for children with ALL
      in first isolated or combined bone marrow relapse defined at high risk according
      to the length of first remission and the immunophenotype. The treatment plan
      included the combination of a single high-dose idarubicin and high-dose
      cytarabine as induction therapy followed by an intensive consolidation and stem
      cell transplant (SCT). In total, 100 children from 16 Italian centres were
      enrolled; 80 out of the 99 evaluable patients (81%) achieved second complete
      remission; eight (8%) died during induction and 11 (11%) failed to respond. A
      total of 42 out of the 80 responders (52.5%) received a SCT: 19 from an identical
      sibling, 11 from a matched unrelated donor and 12 from umbilical cord blood
      cells. The estimated 4-year overall survival and event-free survival were 25% and
      21% respectively. Disease-free survival at 4 years was 25.8% for the 80
      responders. At 4 years, 39 out of 100 children remain alive, with 27 of them free
      of leukaemia. This induction therapy has shown antileukaemic efficacy with
      acceptable toxicity; moreover, all responders proved eligible for intensive
      consolidation.

PMID- 12181041
TI  - High-dose cytarabine in upfront therapy for adult patients with acute
      lymphoblastic leukaemia.
AB  - In this national study, we have evaluated a new intensive chemotherapy protocol
      for adult patients with untreated acute lymphoblastic leukaemia (ALL). One
      hundred and fifty-three patients with median age 42 years received induction
      therapy with high-dose cytarabine (Ara-C), cyclophosphamide, daunorubicin,
      vincristine and betamethasone. A high complete remission (CR) rate (90%) was
      achieved in patients < 60 years compared with 70% in patients > 60 years (P =
      0.004). The estimated 3 year overall survival for all patients was 29% (CI 21
      36%) and the estimated continuous complete remission (CCR) at 3 years for the
      patients achieving CR according to the protocol was 36% (CI 27-45%). A favourable
      pretreatment characteristic was pre-B phenotype, especially for patients < 40
      years without any high-risk factor, with an estimated CCR at 3 years of 62% (CI
      41-82%). Stem cell transplantation (SCT) as post-remission therapy, mainly for
      high-risk patients, gave an estimated 3 year disease free survival (DFS) after
      SCT of 39% (CI 24-54%). No significant differences in DFS could be found between
      autologous, related or unrelated donor transplantation. We conclude that this
      intensive protocol resulted in a high CR rate combined with acceptable side
      effects and a favourable CCR for patients with pre-B ALL.

PMID- 12181042
TI  - Quantification improves the prognostic value of CD38 expression in B-cell chronic
      lymphocytic leukaemia.
AB  - Recent studies have shown that CD38 expressed as a percentage of the antigen
      positivity can predict prognosis and disease progression in patients with B-cell
      chronic lymphocytic leukaemia (B-CLL). The present study showed that
      quantification of CD38 expressed as antibody-binding capacity (ABC) improves the
      prognostic value of the percentage of CD38 positivity in B-CLL. In a cohort of 81
      patients with B-CLL, a level of CD38 expression of > or = 30% and an ABC value of
      250 proved statistically valid cut-off points to predict disease progression (%
      CD38: P=0.0027; ABC: P < 0.0001). There was a positive and significant
      correlation between the percentage of CD38 expression and ABC (r=0.7; P <
      0.0001). There was a better discrimination of survival using ABC rather than
      percentage CD38 positivity (P < 0.0001 compared with P=0.0027). Only ABC
      predicted for survival in patients under 60 years of age (P=0.0076) or with stage
      A disease (P=0.0195). Both percentage CD38 and ABC discriminated between time to
      first treatment for all patients but only ABC predicted time to treatment for
      stage A patients (P=0.0004). In conclusion, CD38 positivity is an important
      prognostic factor in B-CLL. However, quantification of CD38 is superior to the
      percentage positivity and should be used clinically in conjunction with other
      variables of predictive value to identify B-CLL patients that are likely to
      progress.

PMID- 12181043
TI  - The post-transplant cytogenetic response to interferon is a major determinant of
      survival after autologous stem cell transplantation for chronic myeloid leukaemia
      in chronic phase.
AB  - We have analysed the outcome of 581 autologous stem cell transplants (SCT) for
      chronic myeloid leukaemia (CML) in first chronic phase reported to the European
      Group for Blood and Marrow Transplantation between 1983 and 1998. Out off 207
      patients evaluable for cytogenetics within 6 months of SCT, 36 patients (17%)
      were in complete cytogenetic remission (CCR), 34 (16%) in major remission (MCR),
      74 (36%) in minor remission (mCR) and 63 (31%) had no cytogenetic response (NR).
      Interferon (IFN) was given post SCT to 267 patients. Results of the cytogenetic
      analysis within 1-2 years from SCT were available for 117 patients, the majority
      of whom (n = 101) received IFN post SCT: 17 (15%) were in CCR, 18 (15%) in MCR,
      24 (20%) in mCR and 58 (50%) NR. The median survival in this series was 96 months
      (71-125) from SCT. There was no difference in survival according to cytogenetic
      status pre- and immediately post SCT. However, patients in CCR or MCR at 1-2
      years post SCT had a 10-year survival of 66% compared with 36% for patients in
      mCR or NR (P = 0.003). The 5-year survival for patients receiving IFN post SCT
      was 72% compared with 61% for patients not treated with IFN (P = 0.01). Out of
      155 patients refractory to IFN pre SCT, 70% achieved a cytogenetic response post
      SCT, which was complete or major in 31%. IFN refractory patients who sustained a
      CCR or MCR for 1-2 years after SCT had an excellent outcome.

PMID- 12181044
TI  - Serial monitoring of BCR-ABL by peripheral blood real-time polymerase chain
      reaction predicts the marrow cytogenetic response to imatinib mesylate in chronic
      myeloid leukaemia.
AB  - Imatinib mesylate (trade name Glivec or Gleevec) is emerging as an important
      therapy in the management of chronic myeloid leukaemia (CML). It is clinically
      useful to monitor the cytogenetic response to imatinib, although frequent marrow
      examinations are inconvenient. We have used serial real-time reverse
      transcription-polymerase chain reaction (RT-PCR) to monitor the ratio of
      peripheral blood BCR-ABL to normal ABL transcripts in 43 patients receiving
      imatinib, and compared the results to concurrent conventional bone marrow (BM)
      cytogenetics. After 6 months of treatment, 13 cases were complete cytogenetic
      responders, defined as all BM metaphases negative for the Philadelphia (Ph)
      chromosome. In these patients, the BCR-ABL/ABL ratio was less than 0.08%. Six
      cases achieved a partial cytogenetic response (1-35% Ph-positive BM metaphases)
      and their BCR-ABL/ABL ratio was between 0.08 and 10%. In total, 24 cases were
      cytogenetic non-responders, and their BCR-ABL/ABL ratio exceeded 11%. The data
      suggested that the 6-month BCR-ABL/ABL ratio may reliably predict the
      contemporary marrow cytogenetic response. It was concluded that serial real-time
      RT-PCR may offer a convenient surrogate assessment of the marrow cytogenetic
      response to imatinib therapy in CML.

PMID- 12181045
TI  - Natural cytotoxicity to autologous antigen-pulsed dendritic cells in multiple
      myeloma.
AB  - To analyse autologous lymphocyte cytolytic activities of potential importance for
      cell-based immunotherapy in multiple myeloma (MM), in vitro differentiated
      dendritic cells (DCs) loaded with patient-specific monoclonal immunoglobulin
      (mIg) were used as autologous target cellsin cytotoxicity assays. Effector
      populations consisted of purified natural killer (NK) cells (CD56+, CD3-) and T
      cells (CD3+). The MM patients' NK cells cultured in the presence of interleukin 2
      (IL-2) showed pronounced cytotoxic activity towards autologous mature DCs.
      Autologous MM DC targets displayed similar susceptibility to NK cell lysis,
      compared with allogeneic control DC targets, despite high surface expression of
      self major histocompatibility complex (MHC) antigens. However, some degree of
      classic MHC class I-mediated negative regulation was implicated in the NK-DC
      interactions, as indicated by class I blocking experiments. NK-mediated lysis was
      also discerned towards primary autologous MM cells. The results indicated that
      the major effector mechanism was mediated through the perforin-granzyme
      exocytosis pathway. In conclusion, NK cells from MM patients displayed
      significant and consistent cytotoxicity towards autologous mature DCs, suggesting
      that innate immunity could be implicated in MM and may influence the outcome of
      the administration of tumour antigen-pulsed DCs in treatment trials.

PMID- 12181046
TI  - Myelofibrosis with myeloid metaplasia following essential thrombocythaemia:
      actuarial probability, presenting characteristics and evolution in a series of
      195 patients.
AB  - Myelofibrotic transformation is a known complication of essential
      thrombocythaemia (ET), but information on its incidence, presenting features and
      evolution is scarce. In a series of 195 patients with ET followed for a median of
      7.2 years (range: 1.9-24), evolution into myelofibrosis with myeloid metaplasia
      (MMM) occurred in 13 cases, a median of 8 years (range: 3.6-20.2) from diagnosis.
      The actuarial probability of this complication was 2.7% (95% CI: 2.4-2.9) at 5
      years, 8.3% (95% CI: 7.8-8.9) at 10 years, and 15.3% (95% CI: 6.1-24.5) at 15
      years. Four patients had not been treated before developing MMM. The main
      features indicating this condition were the appearance of immature myeloid
      precursors in the peripheral blood, a decrease in the Hb value not related to
      treatment and increased serum lactate dehydrogenase levels, followed by a
      progressive decrease in the platelet count, increasing leucocytosis and
      progressive splenomegaly. No patient had constitutional symptoms, and none of
      five evaluable cases showed chromosome abnormalities in bone marrow or
      unstimulated blood. After a median the myelofibrotic transformation, three
      patients have died and four have not required treatment for MMM as yet.

PMID- 12181047
TI  - Isolation of differentially expressed genes in NPM-ALK-positive anaplastic large
      cell lymphoma.
AB  - In this study, we used subtractive suppression hybridization to compare gene
      expression between an ALK-positive anaplastic large cell lymphoma (ALCL)-derived
      cell line and a clinical case of ALK-negative ALCL. Construction and screening of
      a subtracted library resulted in the cloning of 29 cDNAs which were
      differentially expressed. Most of these clones corresponded to novel genes with
      unknown function (EST) or to genes implicated in the differentiation, activation
      or signalling of T cells such as Ran/TC4, interleukin 1-receptor, thymosin beta4,
      thymosin beta10, moesin and cytohesin-1. Other genes involved in the regulation
      of apoptosis, such as human inhibitor of apoptosis-1 (HIAP-1), Bax inhibitor-1
      and MCL-1, or DNA repair, such as poly (ADP-ribose) polymerase 1 (PARP-1), X
      associated protein-1 (XAP-1), SUMO-1 (sentrin-1) and RanGTPase-activating protein
      1 (RanGAP-1), were isolated. Interestingly, we found that both RNA and protein
      levels of human sterol isomerase (hSI), also referred to as emopamil binding
      protein (EBP), were overexpressed in ALK+ tumours. This protein is involved in
      the biosynthesis of cholesterol and may be activated by NPM-ALK. Overall, our
      results suggest that all the genes described above are upregulated in the NPM-ALK
      driven transformation process, and that moesin and cytohesin-1 may be more
      specifically implicated in a signalling pathway involving PLCgamma and PI3K.

PMID- 12181048
TI  - Safety of allogeneic Epstein-Barr virus (EBV)-specific cytotoxic T lymphocytes
      for patients with refractory EBV-related lymphoma.
AB  - Epstein-Barr virus (EBV) causes lymphomas in immunocompromised individuals such
      as recipients of stem cell or organ transplants and patients with acquired
      immunodeficiency syndrome (AIDS). EBV has also been detected in the Reed
      Sternberg cells of approximately 50% of all cases of Hodgkin's disease (HD). The
      purpose of this study was to examine the safety, and the clinical and
      immunological effects of infusing allogeneic EBV-specific cytotoxic T lymphocytes
      (CTL) for patients with refractory EBV-positive malignancies. In this pilot
      study, we have treated four patients with EBV-related lymphoma using allogeneic
      EBV-specific CTL. Two patients received EBV-specific CTL derived from partially
      human leucocyte antigen (HLA)-matched donors and the other two from HLA-matched
      siblings. No complications were observed as a result of the CTL infusions and all
      patients showed increased levels of EBV-specific CTL precursors (CTLp) post
      infusion. Of the two organ transplant patients, one had refractory disease and
      has sustained a complete remission following the T-cell infusions. The second has
      also been disease free since T-cell infusions, although the efficacy cannot be
      definitively attributed to CTL therapy because this patient received local
      radiation therapy prior to immunotherapy. A patient with AIDS-related, EBV
      positive lymphoma had disease progression following CTL infusions. One HD patient
      received HLA 4/6 matched T cells from an unrelated donor and showed a decrease in
      the size of affected lymph nodes and resolution of B-symptoms post infusion. In
      conclusion, adoptive immunotherapy with allogeneic EBV-specific CTL is safe and
      may have efficacy in patients with high-risk or refractory EBV-related tumours.

PMID- 12181049
TI  - Differentiation between non-Hodgkin's lymphoma recurrence and second primary
      lymphoma by VDJ rearrangement analysis.
AB  - Relapses in non-Hodgkin's lymphomas (NHL) could be due to the reappearance of the
      initial neoplasm or new primary tumours. Discrimination between the two events
      would allow a more targeted therapeutic approach. VDJ rearrangement was used as
      marker of clonality in metachronous biopsy specimens from 10 patients with
      relapsed B-NHL. Complimentary determining region 3 was amplified and sequenced. D
      JH was identical in eight matched primary/secondary tumours, confirming the
      diagnosis of recurrence. In contrast, primary and secondary tumours in two
      patients were of different clonal origin. Our data indicate that VDJ analysis is
      a fundamental tool for identification of relapses in NHL.

PMID- 12181050
TI  - Low-dose, single-fraction, whole-lung radiotherapy for pulmonary hypertension
      associated with myelofibrosis with myeloid metaplasia.
AB  - Pulmonary hypertension (PH) can complicate myelofibrosis with myeloid metaplasia
      (MMM), may arise in the absence of evidence for thromboembolic disease and
      carries a grim prognosis. Four patients with MMM and severe symptomatic PH were
      treated with whole-lung external beam radiotherapy in a single fraction of 100
      cGy. Within 72 h, each patient noted marked symptomatic improvement and had
      relief of hypoxia and reduction of oedema and/or ascites. Three of the four
      patients enjoyed an objective improvement in pulmonary artery systolic pressure
      as measured by transthoracic Doppler echocardiography. Low-dose lung radiotherapy
      may be a useful palliative tool for patients with MMM complicated by PH.

PMID- 12181052
TI  - Strontium-89: a novel treatment for a case of osteosclerotic myeloma associated
      with life-threatening neuropathy.
AB  - Osteosclerotic myeloma is a rare disorder characterized by paraproteinaemia and
      osteosclerosis, and may be associated with a progressive peripheral neuropathy.
      Patients with widespread osteosclerotic lesions can succumb from neurological
      complications despite systemic chemotherapy. We present a case of disseminated
      osteosclerotic myeloma associated with POEMS (peripheral neuropathy,
      organomegaly, endocrinopathy, M band, skin changes) syndrome, which was
      complicated by a rapidly progressive, life-threatening neuropathy. The patient's
      symptoms remained unchanged in the face of combination chemotherapy. However, a
      substantial improvement was seen following outpatient treatment with the commonly
      available radioisotope strontium 89 in combination with steroids.

PMID- 12181051
TI  - Microvessel density, a surrogate marker of angiogenesis, is significantly related
      to survival in multiple myeloma patients.
AB  - We evaluated microvessel density (MVD) in bone marrow biopsies (BM) from multiple
      myeloma (MM) patients after staining with anti-CD34 and anti-CD105 antibodies
      (mAbs). The anti-CD105 mAb was significantly more sensitive than the anti-CD34
      mAb in visualizing blood vessels both in controls and MM samples. MVD was
      significantly higher in MM than in controls with both anti-CD34 and anti-CD105
      mAbs. Patients with low CD34+ MVD survived longer than patients with higher MVD
      (P = 0.01), whereas there was no difference in survival between patients with low
      and high CD105+ MVD. Multivariate analysis confirmed the independent significant
      association between CD34+ MVD and survival (P = 0.001).

PMID- 12181053
TI  - Factor XIII A-subunit concentration predicts outcome in stroke subjects and
      vascular outcome in healthy, middle-aged men.
AB  - There is growing evidence for a role of factor XIII (FXIII) in vascular disease.
      FXIII measures were determined in (i) a nested case-control study from the Second
      Northwick Park Heart Study of 63 men with myocardial infarction (MI) and 124 age
      matched controls and (ii) in a case-control study of 475 subjects with acute
      stroke and 461 controls followed up for 54 months for mortality. In both studies,
      measures of FXIII A- and B-subunit antigen, FXIII activity and prothrombin
      fragments (F1 + 2) were made. An in vitro model was used to investigate the
      effects of thrombin activity on FXIII A- and B-subunit antigen levels. In study
      1, patients clinically free of coronary artery disease who later developed MI had
      lower adjusted FXIII A-subunit levels at recruitment (129.2%vs 113.3%, P =
      0.007). In study 2, stroke patients with large vessel disease had lower A-subunit
      antigen levels (102.1%vs 127.2%, P < 0.001), but higher F1 + 2 levels (0.941%vs
      0.753%, P < 0.05), than subjects with small vessel disease. Levels of FXIII A
      subunit (100%vs 117%, P < 0.0001) were lower and F1 + 2 higher (1.020%vs 0.702%,
      P < 0.0001) in stroke patients who had died compared with those still alive at
      the end of the follow-up period. Low concentrations of FXIII A-subunit antigen
      predicted vascular outcome in otherwise healthy subjects and relate to both size
      of infarct and poor post-stroke survival in patients with acute ischaemic stroke.
      Low in vitro concentrations of FXIII A-subunit antigen wererelated to increased
      thrombin generation and, thus, increased risk of thrombotic events.

PMID- 12181054
TI  - A Leu55 to Pro substitution in the integrin alphaIIb is responsible for a case of
      Glanzmann's thrombasthenia.
AB  - Glanzmann's thrombasthenia (GT) is a hereditary bleeding disorder caused by a
      quantitative or qualitative defect in the integrin alphaIIbbeta3. A new mutation,
      a T to C substitution at base 258 in the alphaIIb gene, leading to the
      replacement of Leu55 with Pro, was found by sequence analysis of a patient's
      alphaIIb cDNA. In transfection experiments using COS7 cells, the cells co
      transfected with the mutated alphaIIb cDNA containing C258 and wild-type beta3
      cDNA scarcely expressed the alphaIIbbeta3 complex. The Leu55 to Pro substitution
      in the alphaIIb gene was found to be responsible for this case of Glanzmann's
      thrombasthenia.

PMID- 12181055
TI  - High P-glycoprotein-mediated export observed in patients with a history of
      idiopathic thrombocytopenic purpura.
AB  - Studies have suggested that high P-glycoprotein expression in lymphocytes from
      patients with autoimmune disorders may affect disease outcome. Idiopathic
      thrombocytopenic purpura (ITP) and Evans' syndrome are widely thought to be
      autoimmune processes, however, the precise mechanisms remain unknown. Peripheral
      blood mononuclear cells from patients with refractory or recurrent ITP or Evans'
      syndrome were studied using the rhodamine 123 flow cytometric assay to
      investigate functional export levels. Lymphocytes from ITP and Evans' syndrome
      patients showed a significantly decreased ability to retain rhodamine, suggesting
      increased export protein function. Reverse transcription polymerase chain
      reaction distinguished P-glycoprotein as the likely export protein.

PMID- 12181056
TI  - Use of a non-depleting anti-CD4 antibody to modulate the immune response to
      coagulation factors VIII and IX.
AB  - The generation of antibodies to therapeutic factors VIII or IX is a major problem
      in the management of haemophilia and places potential limitations on the
      application of gene therapy. We have investigated the administration of a non
      depleting anti-CD4 antibody for modulation of the immune response to human
      recombinant coagulation factors VIII and IX. In mice given these clotting
      factors, co-administration of anti-CD4 antibody significantly reduced the
      appearance of factor-specific antibodies. These data provide evidence that the
      neutralizing antibody response to exogenous coagulation factors may be
      controllable if non-depleting anti-CD4 antibody is co-administered at the time of
      initial replacement therapy.

PMID- 12181057
TI  - The effect of plasma caeruloplasmin levels on the sensitivity for activated
      protein C.
AB  - The effect of caeruloplasmin levels on the sensitivity for activated protein C
      (APC), measured by a clotting assay based on the activated partial thromboplastin
      time, was investigated in a large group of healthy individuals without factor V
      Leiden. A modest inverse association between caeruloplasmin and normalized APC
      sensitivity ratio was found (regression coefficient beta = -0.33 x 10-2; 95%
      confidence interval, -0.42 x 10-2 to -0.24 x 10-2). After adjustment for sex and
      oral contraceptive use, this association weakened (beta = -0.19 x 10-2; 95% CI: 
      0.34 x 10-2 to -0.05 x 10-2). After additional adjustment for factor VIII levels,
      which are known to influence the assay, the effect of caeruloplasmin on APC
      sensitivity completely disappeared.

PMID- 12181058
TI  - Influence of lineage-specific cytokines on commitment and asymmetric cell
      division of haematopoietic progenitor cells.
AB  - We examined the influence of cytokines on erythroid- and myeloid-lineage
      development of AC133+ cells during primary and secondary cultures. Cells cultured
      for 14 d in liquid medium containing erythropoietin (EPO) were amplified 831-fold
      with 98.2% erythroid cells. A similar culture exposed to granulocyte colony
      stimulating factor (G-CSF) grew 1350-fold with 97.4% myeloid cells. To assess
      whether the cells with EPO inducement could respond at this point to G-CSF
      signal, or vice versa, the EPO-stimulated population was re-grown with G-CSF,
      constituting 95.2% myeloid, of 5075-fold, cells after 14 d of re-culture.
      Conversely, reculture of the G-CSF-stimulated population with EPO resulted in a
      4083-fold growth with 81.4% erythroid cells. Semisolid culture containing EPO orG
      CSF showed that some individual colonies had self- renewal potential after 14 d
      culture and could be induced todevelop into a different lineage. Analysis of
      primitive markers, CD34 and Notch1, or lineage markers, EPO-R and CD13, by single
      cell reverse transcription polymerase chain reaction showed that individual
      colonies of 2-16 cells contained at least one CD34-positive cell with expression
      ofNotch1 and co-expression of EPO-R and CD13 appeared on either CD34-positive or
      CD34-negative cells. In situ hybridization with the same cell surface markers in
      cell populations confirmed the asymmetric cell division and co-expression from
      single cell data. The study provides a useful model for the analysis of
      multipotential progenitor development, and indicates that progenitor cells co
      express genes from different lineage pathways before commitment and that
      cytokines influence lineage commitment.

PMID- 12181059
TI  - The role of common gamma chain in human monocytes in vivo; evaluation from the
      studies of X-linked severe combined immunodeficiency (X-SCID) carriers and X-SCID
      patients who underwent cord blood stem cell transplantation.
AB  - Expression of common gamma chain (gammac) on monocytes was studied in five
      carriers of X-linked severe combined immunodeficiency (X-SCID) and two X-SCID
      patients who underwent cord blood stem cell transplantation (CBSCT). Flow
      cytometric analysis revealed that both gammac-negative and positive monocytes co
      existed in X-SCID carriers, whereas no gammac-negative T, B or NK cells were
      observed in them. Clonal analysis and reverse transcription polymerase chain
      reaction studies revealed that 13.2-45.0% of monocytes from these carriers
      expressed the mutant gammac message. X-SCID patients who received CBSCT
      persistently possessed the majority of gammac-negative monocytes with a good
      clinical course. These results, together, may indicate that gammac is not
      essential for monocyte development/function in vivo.

PMID- 12181060
TI  - Improvement of interleukin 2 production, clonogenic capability and restoration of
      stromal cell function in human immunodeficiency virus-type-1 patients after
      highly active antiretroviral therapy.
AB  - Haematological abnormalities frequently occur in patients infected by human
      immunodeficiency virus-type 1 (HIV-1). Increasing evidence indicates that bone
      marrow suppression (BM) results from viral infection of accessory cells, with
      impaired stromal function and alteration of haematopoietic growth factor network.
      We have investigated the effects of antiretroviral therapy on cytokine and
      chemokine production by BM cells and stromal cells in a group of HIV-1-infected
      subjects before and during treatment. Compared with uninfected controls, an
      altered cytokine and chemokine production by BM cells was observed before
      treatment, characterized by decreased interleukin 2 (IL-2) and elevated tumour
      necrosis factor-alpha, macrophage inflammatory protein (MIP)-1alpha, MIP-1beta,
      and RANTES (regulated on activation, normal T cell-expressed and secreted)
      levels, along with a defective BM clonogenic activity. Antiretroviral therapy
      showed increased BM clonogenic capability, associated with normalization of IL-2
      production and chemokine receptors expression on CD34+ cells. Pre-therapy, BM
      accessory cells were represented by macrophage-like cells, in some cases positive
      for HIV-1 DNA, suggesting that these cells are the main target of HIV-1
      infection. During therapy, the stromal cells became predominantly fibroblastoid
      like, as observed in normal controls, and were negative for HIV-1 DNA.
      Controlling HIV-1 replication may produce amelioration of stem cell activity, and
      restoration of stromal cell pattern and functions, with increased IL-2 production
      at BM level.

PMID- 12181061
TI  - Retroviral interleukin 1alpha gene transfer in bone marrow stromal cells in a
      primate model: induction of myelopoiesis stimulation.
AB  - Effects of interleukin 1-alpha (IL-1alpha), a proinflammatory cytokine with
      pleiotropic activity, in the myelopoietic setting, is mainly linked to its
      ability to increase haematopoietic growth factor production by bone marrow
      stromal cells. In order to minimize systemic effects of IL-1alpha therapy, we
      proposed a model of retroviral IL-1alpha gene transfer within bone marrow stromal
      cells in the macaque cynomolgus. Invitro, 10-15% of bone marrow stromal cells was
      effectively transduced by retroviral vector (murine Moloney leukaemia virus
      derived) expressing IL-1alpha/LacZ, or LacZ alone as control marker, as assessed
      by betaGal staining. IL-1alpha gene expression was upregulated [semiquantitative
      reverse transcription polymerase chain reaction (RT-PCR)] within the transduced
      cells and the cell supernatant showed an increased production of granulocyte
      colony-stimulating factor (G-CSF) and granulocyte-macrophage (GM)-CSF (enzyme
      linked immunosorbent assay) and an increased clonogenic activity (colony-forming
      cell assay). Ex vivo autologous expanded IL-1alpha/LacZ transduced bone marrow
      stromal cells were reinfused in two macaques (and two control animals for LacZ
      alone as controls), without clinical systemic toxicity; LacZ expression by RT-PCR
      was detected in one animal of each group between d 4 and 9. A slight increase of
      the peripheral blood leucocyte counts (both polymorphonuclear cells and
      monocytes) of the two animals transduced with IL-1alpha/LacZ was observed within
      10 d, indicating stimulation of myelopoiesis.

PMID- 12181062
TI  - Human natural killer cell development in a xenogeneic culture system.
AB  - In vivo and in vitro xenogeneic models have shown the ability of a non-human
      environment in supporting human haemopoiesis. In the present study, we evaluated
      the effect of fetal sheep thymic stroma in the in vitro development of natural
      killer (NK) cells from human haemopoietic progenitors. CD34+HLA-DR+ (CD34+
      DR+)Lin- and CD34+DR-Lin- bone marrow (BM) progenitors were cultured for 3 weeks
      with or without interleukin 2 (IL-2), in fetal sheep thymic stroma contact and
      transwell cultures. Both progenitors gave rise to NK cells, defined as CD45+CD56+
      cells, in the presence or absence of IL-2; however, the percentage of NK cells
      originated in cultures with IL-2 was significantly higher. Direct contact with
      stroma seemed to be required for the most immature progenitors, CD34+DR-Lin-, to
      differentiate along the NK cell lineage. Functional assays revealed that only
      cells grown in the presence of IL-2 were cytolytic against K562 targets and,
      curiously, NK cells derived from CD34+DR-Lin- progenitors were more cytotoxic
      that NK cells derived from CD34+DR+Lin- progenitors. These studies suggest that
      the ability of fetal sheep thymic stroma in promoting the generation of human NK
      cells from haemopoietic progenitors may have relevance in terms of NK cell
      ontogeny and induction of tolerance in transplantation.

PMID- 12181063
TI  - Relationship between hypercoagulable state and erythrocyte phosphatidylserine
      exposure in splenectomized haemoglobin E/beta-thalassaemic patients.
AB  - Small pulmonary arterial thromboses can occur following splenectomy of patients
      with haemoglobin E/beta-thalassaemia (Hb E/beta-thal). We compared plasma markers
      of coagulation activation in vivo and red blood cell (RBC) markers of
      procoagulant activity in 15 Hb E/beta-thal patients who were not splenectomized
      (NS), 15 who had been splenectomized (S), and 15 normal controls (NC). Levels of
      plasma thrombin-antithrombin III complex (TAT) were significantly higher in the S
      group than in either the NS or the NC groups, and levels of prothrombin fragment
      1.2 (F 1.2) were significantly higher in the S than in the NC group. Diluted
      Russell's viper venom clotting times were significantly shorter when RBCs from
      group S patients were added to the assay compared with RBCs from the NC group.
      Phosphatidylserine (PS) expression (% of annexin V-positive RBCs) on the outer
      leaflet of RBC membrane of both 'larger'- and 'smaller'-sized RBCs was
      significantly higher for the S than the NC group. The RBC PS expression of the S
      and the NS groups, respectively, accounted for 25 x 3% (P = 0 x 174) and 6.3% (P
      = 0 x 675) of the variation in plasma TAT levels. Our findings indicated that,
      when compared with NC, splenectomized patients with Hb E/beta-thal were in a
      chronic low-grade hypercoagulable state associated with increased numbers of
      circulating PS exposed RBCs. This condition may have a role in the risk of these
      patients for pulmonary arterial thromboses.

PMID- 12181064
TI  - Glycophorin A-mediated haemolysis of normal human erythrocytes: evidence for
      antigen aggregation in the pathogenesis of immune haemolysis.
AB  - The inexplicable severity of anti-Pr autoimmune haemolytic anaemia led us to test
      the hypothesis that the haemolysis was primarily due to a change in the function
      of glycophorin A, on which the Pr antigen is located. The lectins Maclura
      pomifera and wheat germ agglutinin that bind to glycophorin A induced the
      haemolysis of normal erythrocytes in vitro. Lectin binding led to an increase in
      erythrocyte membrane permeability to sodium and potassium, the former resulting
      in an influx of water and subsequent haemolysis. The response was glycophorin A
      specific as Concanavalin A, which binds to band 3, did not cause haemolysis and
      peanut agglutinin only did so after removal of erythrocyte sialic acid. The
      lectin-induced cation leak was not mediated by activation of cation channels as
      the inhibitors, tetrodotoxin, amiloride and 4,4' disothiocyanate stilbene
      2,2'disulphonate, had no effect, suggesting that the haemolysis was due to
      exacerbation of the inherent cation permeability of the erythrocyte membrane. A
      human IgAK anti-Pr autoantibody and a mouse anti-human glycophorin A antibody
      increased erythrocyte permeability to sodium. The role of glycophorin A in
      stabilizing and, upon aggregation, destabilizing the phospholipid bilayer is
      discussed. Our findings may help explain the severity of anti-Pr autoimmune
      haemolytic anaemia and other pathophysiological changes in human erythrocytes.

PMID- 12181065
TI  - Enforced expression of HOX11 is associated with an immature phenotype in J2E
      erythroid cells.
AB  - The HOX11 gene encodes a homeodomain transcription factor that is essential for
      spleen development during embryogenesis. HOX11 is also leukaemogenic, both
      through its clinical association with childhood T-cell acute lymphoblastic
      leukaemia, and its ability to immortalize other haematopoietic cell lineages
      experimentally. To examine the pathological role of HOX11 in tumorigenesis, we
      constitutively expressed HOX11 cDNA in J2E murine erythroleukaemic cells, which
      are capable of terminal differentiation. Enforced HOX11 expression was found to
      induce a profound alteration in J2E cellular morphology and differentiation
      status. Our analyses revealed that HOX11 produced clones with a preponderance of
      less differentiated cells that were highly adherent to plastic. Morphologically,
      the cells overexpressing HOX11 were larger and had decreased globin levels, as
      well as a reduction in haemoglobin synthesis in response to erythropoietin (EPO).
      Immunocytochemical analysis confirmed the immature erythroid phenotype imposed by
      HOX11, with clones transfected with HOX11 demonstrating expression of the c-Kit
      stem cell marker, while retaining EPO receptor expression. Taken together, these
      results show that HOX11 alters erythroid differentiation, favouring a less mature
      progenitor-like stage. This supports the notion that disrupted haematopoietic
      cell differentiation is responsible for pre-leukaemic immortalization by the
      HOX11 oncoprotein.

PMID- 12181066
TI  - Etilefrine for the prevention of priapism in adult sickle cell disease.
AB  - Priapism is a common complication of sickle cell disease (SCD) that could lead to
      erectile dysfunction and psychosocial problems. Treatment of established
      fulminant priapism is usually not satisfactory. It is therefore important to
      prevent this complication of SCD. The alpha-adrenergic agonist etilefrine (50-100
      mg/d) produced a good clinical response in 13 of 18 (72%) adults who have
      recurrent priapism; 17 had SCD and one sickle cell trait. After a follow-up of 1
      48 months, none of the 18 people on etilefrine developed hypertension or sexual
      dysfunction. Similar efficacy and safety profiles of the drug have been reported
      previously.

PMID- 12181067
TI  - Time for a redefinition of type 2M von Willebrand disease.

PMID- 12181068
TI  - Polyclonal hypergammaglobulinaemia with hyperviscosity syndrome.

PMID- 12181069
TI  - Possibility of somatic mosaicism of ELA2 mutation overlooked in an asymptomatic
      father transmitting severe congenital neutropenia to two offspring.

PMID- 12181071
TI  - The use of vitamin K for reversal of over-warfarinization in children.

PMID- 12181072
TI  - Reversal of coumarin-induced over-anticoagulation.

PMID- 12181074
TI  - Consequences at mRNA level of the PKLR gene splicing mutations IVS10(+1)G-->C and
      IVS8(+2)T-->G causing pyruvate kinase deficiency.

PMID- 12181075
TI  - Regarding the loss of CD20 after rituximab therapy.

PMID- 12181080
TI  - Policy mapping for establishing a national emergency health policy for Nigeria.
AB  - BACKGROUND: The number of potential life years lost due to accidents and injuries
      though poorly studied has resulted in tremendous economic and social loss to
      Nigeria. Numerous socio-cultural, economic and political factors including the
      current epidemic of ethnic and religious conflicts act in concert in predisposing
      to and enabling the ongoing catastrophe of accident and injuries in Nigeria.
      METHODS: Using the "policymaker", Microsoft-WindowscircledR; based software, the
      information generated on accidents and injuries and emergency health care in
      Nigeria from literature review, content analysis of relevant documents, expert
      interviewing and consensus opinion, a model National Emergency Health Policy was
      designed and analyzed. A major point of analysis for the policy is the current
      political feasibility of the policy including its opportunities and obstacles in
      the country. RESULTS: A model National Emergency Health Policy with policy goals,
      objectives, programs and evaluation benchmarks was generated. Critical analyses
      of potential policy problems, associated multiple players, diverging interests
      and implementation guidelines were developed. CONCLUSIONS: "Political health
      modeling" a term proposed here would be invaluable to policy makers and scholars
      in developing countries in assessing the political feasibility of policy
      managing. Political modeling applied to the development of a NEHP in Nigeria
      would empower policy makers and the policy making process and would ensure a
      sustainable emergency health policy in Nigeria.

PMID- 12181081
TI  - Sex steroids do not affect shigatoxin cytotoxicity on human renal tubular or
      glomerular cells.
AB  - BACKGROUND: The greater susceptibility of children to renal injury in post
      diarrheal hemolytic-uremic syndrome (HUS) may be related, at least in part, to
      heightened renal cell sensitivity to the cytotoxic effect of Shiga toxin (Stx),
      the putative mediator of kidney damage in HUS. We hypothesized that sexual
      maturation, which coincides with a falling incidence of HUS, may induce a
      relatively Stx-resistant state in the renal cells. METHODS: Cultured human
      glomerular endothelial (HGEN), human glomerular visceral epithelial (HGEC) and
      human proximal tubule (HPT) cells were exposed to Stx-1 after pre-incubation with
      progesterone, beta-estradiol or testosterone followed by determination of
      cytotoxicity. RESULTS: Under basal conditions, Stx-1 potently and dose
      dependently killed HPT and HGEC, but had relatively little effect on HGEN. Pre
      incubation for 1, 2 or 7 days with physiologic or pharmacologic concentrations of
      progesterone, beta-estradiol or testosterone had no effect on Stx-1 cytotoxicity
      dose-response on any cell type. In addition, no steroid altered Gb3 expression
      (Stx receptor) by any cell type at any time point. CONCLUSION: These data do not
      support the notion that hormonal changes associated with puberty induce an Stx
      resistant state within kidney cells.

PMID- 12181083
TI  - [Clinical efficacy and safety of huperzine Alpha in treatment of mild to moderate
      Alzheimer disease, a placebo-controlled, double-blind, randomized trial].
AB  - OBJECTIVE: To evaluate the clinical efficacy and safety of huperzine Alpha in
      treatment of patients with mild to moderate Alzheimer disease (AD). METHODS: Two
      hundred and two patients with the diagnosis of possible or probable AD from 15
      centers the nationwide were randomly divided into two groups: huperzine Alpha
      group (n = 100, given huperzine Alpha 400 micro g/day for 12 weeks) and placebo
      group (n = 102 ). Different scales were used to evaluate the cognitive function,
      activity of daily life (ADL), non-cognitive disorders, and overall clinical
      efficacy. Safety evaluation was conducted every 6 weeks. RESULTS: In comparison
      with the baseline data, there was an improvement of 4.6 points in cognition
      assessed by ADAS-Cog (P = 0.000); an improvement of 2.7 points by MMSE (P =
      0.000), an improvement of 1.5 points in behavior and mood by ADAS-non-Cog (P =
      0.008) with 59.2% of the patients being on the mend clinically; and an
      improvement of 2.4 points by ADL (P = 0.001) with the capacity of ADL improved by
      at least 10% among 32.75% of the patients. 70% of the patients in huperzine Alpha
      group scored 1 approximately 3 points, and 27.8% of them scored 1 approximately 2
      points by CIBIC-plus. The proportions of patients with an improvement of >/= 4
      points by ADAS-Cog were 56.1% and 12.5% in the huperzine Alpha group and placebo
      group respectively (P = 0.000). The proportions of patients with an improvement
      of >/= 4 points by MMSE were 37.8% and 10.1% in the huperzine Alpha group and
      placebo group respectively (P = 0.000). The proportions of patients with an
      improvement of 1 approximately 3 points in global rating by CIBIC-plus were 59.2%
      and 40.6% in the huperzine Alpha group and placebo group respectively (P = 0.01).
      The proportions of patients with an improvement of >/= 10% points by ADL were
      32.7% and 17.2% in the huperzine Alpha group and placebo group respectively (P =
      0.01). The proportions of patients with an improvement of > 0 points by ADS-non
      C0g were 70.0% and 36.3% in the huperzine Alpha group and placebo group
      respectively (P = 0.000). Mild and transient adverse events (edema of bilateral
      ankles and insomnia) were observed in 3% of huperzine Alpha treated patients.
      CONCLUSION: A safe and effective medicine, huperzine Alpha remarkably improves
      the cognition, behavior, ADL,and mood of AD patients.

PMID- 12181084
TI  - [Changes of pathogenic bacteria in pediatric patients of septicemia and drug
      resistance there of in Zhejiang Children's Hospital 1991 approximately 2000].
AB  - OBJECTIVE: To investigate the changes of pathogenic bacteria detected from the
      blood culture of pediatric patients with septicemia in the past 10 years, and to
      observe the drug resistance thereof in the past two years. METHODS: The blood
      samples of 4 425 pediatric patients aged 0 approximately 14 with the diagnosis of
      septicemia 1991 approximately 2000 in Zhejiang Children's Hospital were cultured
      in broth (1991 approximately 1996) or VITA AER blood culture apparatus (1997
      approximately 2000). Analytic Product Inc. (API ) system and KB paper strip
      method and VITEK automicroscan were used to identify the species and conduct drug
      resistance test. The results were interpreted according to the guideline of
      National Committee for Clinical Laboratory Standards. RESULTS: In the past 10
      years, Gram-positive bacteria remained the more frequent pathogens than Gram
      negative bacteria in pediatric patients with septicemia. The proportion of
      coagulase-negative staphylococcus (CNS) had been increasing and reached 69% in
      2000. The proportions of Staphylococcus aureus and Escherichia coli decreased
      from 35.4% and 18.2% in 1991 to 5.3% and 1.5% in 2000. In the past two years, the
      drug resistance rate of staphylococci against penicillin and erythromycin were
      more than 90% and 70% respectively. The oxacillin resistance rate of CNS was
      60.3%, significantly higher than that of Staphylococcus aureus (10.3%). No strain
      of Staphylococcus and Enterococcus resistant to vancomycin was found. Escherichia
      coli and Psudomonas aeruginosa and other species of Enterobacteriae were
      sensitive to imipenem/cilastin sodium, whereas the resistance rate of them to
      ampicillin and first generation cephalosporins was more than 50%. CONCLUSION: (1)
      Gram-positive bacteria are the predominant pathogens of pediatric patients with
      septicemia, with the species of Staphylococcus ranking first among which CNS is
      the main pathogen for infants and Staphylococcus aureus is the main pathogen for
      school children. (2) Escherichia coli is the most frequently found pathogenic
      Gram-negative bacterium in infants with septicemia whereas Salmonella in school
      children. (3) Drug resistance of isolated pathogenic bacteria in department of
      pediatrics is a serious problem. Monitoring the change of pathogen and the trends
      of antimicrobial resistance is very important in guiding therapy.

PMID- 12181085
TI  - [Working memory impairment in early Parkinson's disease patients].
AB  - OBJECTIVE: To investigate the characteristics of working memory impairment in
      early Parkinson's disease (PD) patients and underlying neuropsychological and
      patho-physiological mechanisms. METHODS: Thirty PD cases and 30 normal controls
      (NCs) were tested with modified Smith's working memory software. RESULTS: The
      correct rate of coordinate working memory in PD cases was 71.2 +/- 11.0%,
      significantly lower than that in the NCs (81.9% +/- 10.8%, t =3.78, P < 0.001).
      The correct rate of categorical working memory was 94.8 +/- 5.7% in the PD cases,
      not significantly different from that in the NCs (96.6% +/- 3.8%, t =1.46, P >
      0.05). CONCLUSION: There is visuo-spatial working memory impairment, mainly
      coordinate spatial working memory impairment, in early PD patients. The
      categorical spatial working memory is relatively intact in early PD. It is
      postulated that the different working memory subsystems apply for different
      neurocircuits.

PMID- 12181082
TI  - Shorter courses of parenteral antibiotic therapy do not appear to influence
      response rates for children with acute hematogenous osteomyelitis: a systematic
      review.
AB  - BACKGROUND: Acute hematogenous osteomyelitis (AHO) occurs primarily in children
      and is believed to evolve from bacteremia followed by localization of infection
      to the metaphysis of bones. Currently, there is no consensus on the route and
      duration of antimicrobial therapy to treat AHO. METHODS: We conducted a
      systematic review of a short versus long course of treatment for AHO due
      primarily to Staphylococcus aureus in children aged 3 months to 16 years. We
      searched Medline, Embase and the Cochrane trials registry for controlled trials.
      Clinical cure rate at 6 months was the primary outcome variable, and groups
      receiving less than 7 days of intravenous therapy were compared with groups
      receiving one week or longer of intravenous antimicrobials. RESULTS: 12 eligible
      prospective studies, one of which was randomized, were identified. The overall
      cure rate at 6 months for the short course of intravenous therapy was 95.2% (95%
      CI = 90.4 - 97.7) compared to 98.8% (95% CI = 93.6, 99.8) for the longer course
      of therapy. There was no significant difference in the duration of oral therapy
      between the two groups. CONCLUSIONS: Given the potential increased morbidity and
      cost associated with longer courses of intravenous therapy, this finding should
      be confirmed through a randomized controlled equivalence trial

PMID- 12181086
TI  - [Quantitative assessment of Parkinsonian rigidity by vessel Doppler
      ultrasonography].
AB  - OBJECTIVE: To investigate the value of quantitative assessment of parkinsonian
      rigidity by vessel Doppler ultrasonography. METHODS: The diameter of the rigid
      limbs, including radial artery and vein, ulnar artery and vein, brachial veins,
      popliteal vein, anterior tibial vein, and posterior tibial vein in twelve
      individuals with PD and twelve age matched controls were measured by
      ultrasonography in both "on" and "off" states. Meanwhile the UPDRS unified
      Parkinson's disease rating scale for rigidity were also recorded both in "on" and
      "off " states by experienced neurologists. RESULTS: The mean diameter of radial
      vein, ulnar vein, brachial vein, popliteal vein, anterior tibial vein and
      posterior tibial vein, were 1.14, 1.13, 2.47, 3.85, 1.89, and 1.33 mm
      respectively in "off " state (group "A"), and were 1.58, 1.54, 2.88, 4.65, 2.27,
      and 1.69 mm respectively in "on" states (group "B") among the PD patients. The
      diameters of corresponding vessels in the controls (group "C") were 2.07, 1.69,
      4.15, 5.07, 2.63, and 1.99 mm respectively. The data increased from group "A" to
      "C" gradually. Paired samples t tested showed a significant difference between
      the data of group A and group B (P = 0.00 approximately 0.03) and between group A
      and group C (P = 0.00 approximately 0.02) and no significant difference between
      group B and group C (P > 0.05, except for brachial vein with P = 0.02). The data
      of vein diameters in rigid limbs were correspondent to the UPDRS scores for
      rigidity with the correlation coefficient of 0.71, 0.82, 0.91, 0.73 (all P <
      0.01), 0.60 P < 0.05 , and 0.77 P < 0.01) for the above mentioned vessels
      respectively. CONCLUSION: The diameter of distant veins in limbs can be adopted
      as objective and quantitative indicators for parkinsonian rigidity and contribute
      to the evaluation of therapeutical effects.

PMID- 12181087
TI  - [Effectiveness of post-exposure prophylaxis using live attenuated hepatitis Alpha
      vaccine (H(2) strain) among schoolchildren].
AB  - OBJECTIVE: To observe the efficacy of emergency immunization to abort hepatitis
      Alpha outbreak using live attenuated hepatitis Alpha vaccine. METHODS: During an
      outbreak of hepatitis Alpha in a village in Zhengding County, Hebei Province, one
      dose of live attenuated hepatitis Alpha vaccine (H(2) strain) was administered to
      92 schoolchildren of two primary schools in that village on a voluntary basis,
      and 189 schoolchildren who were not vaccinated were used as controls. Their serum
      specimens were collected 3 times at different time points (0 and 18 days after
      the vaccination and 40 days after the appearance of the last hepatitis Alpha
      case). The total antibody and IgM of hepatitis Alpha were examined by ELISA.
      Clinical observation was made to discover whether new case appeared. The rates of
      seroconversion and hepatitis Alpha in susceptibles between vaccinated and
      unvaccinated groups were compared. RESULTS: The new infection rate of hepatitis
      Alpha during the 18 days after vaccination was 5.43% in the vaccinated group and
      7.43% in the control group (P > 0.05). The prevalence rate was 0 in both groups
      (P > 0.05). The new infection rate of hepatitis Alpha during the period from the
      18th day after vaccination to the 40th day after the appearance of the last case
      was 2.41% in the vaccinated group and 3.21% in the control group (P > 0.05).
      CONCLUSION: The live attenuated hepatitis Alpha vaccine can not provide post
      exposure protection against infection of hepatitis Alpha virus during the
      outbreak.

PMID- 12181089
TI  - [Detection of Mycoplasma hyorhinis in gastric cancer using bio-chip technology].
AB  - OBJECTIVE: To determine the prevalence of Mycoplasma hyorhinis in archived
      paraffin-embedded gastric cancer tissue and to find whether Mycoplasma hyorhinis
      infection can influence gene expression level in gastric cancer cells. METHODS: A
      high-dense tissue microarray containing 105 gastric cancer samples, 101 benign
      margin samples and 62 non-cancerous gastric disease samples resected during
      operation was constructed. PD4, a specific anti-Mycoplasma-hyorhinis Mab, was
      used to detect the infection rate in all the samples in the tissue microarrays
      immunohistochemically. Then, cDNA microarray was used to pinpoint differentially
      the expressed genes between gastric cancer cell line MGC803 samples with and
      without Mycoplasma hyorhinis infection. RESULTS: The infection rate of M.
      hyorhinis was 54.1% 53/98 in gastric cancer samples, 51.7% 45/87 in benign margin
      samples, and 15.8 % 9/57 in non-cancerous disease samples respectively. The
      difference of infection rates between gastric cancer and non-cancerous gastric
      disease was statistically significant (P = 0.001). Highly differentiated
      adenocarcinomas had more opportunity (84.6%) to be infected with M. hyorhinis
      than poorly differentiated ones (45.9%)(P < 0.05). Intestinal type of gastric
      cancers (according to Lauren's classification) got the infection more often than
      diffused type. About 409 gene expression alterations were detected in 48 000
      sites from two gastric cancer cell lines and the expression levels of some genes
      correlating with cell apoptosis and cell adhesion were down regulated after
      Mycoplasma hyorhinis infection. CONCLUSION: The infection rate of M. hyorhinis is
      significantly higher in gastric cancer than in other gastric diseases, thus
      indicating the association between Mycoplasma infection and gastric cancer.
      Mycoplasma hyorhinis infection influences the gene expression level in gastric
      cancer cell line MGC803, which indicates that the infection could have something
      to do with the process of gastric cancer. The question whether M.hyorhinis has
      oncogenic potential remains to be elucidated.

PMID- 12181088
TI  - [Treatment of chronic hepatitis C by bicyclum, a randomized double-blind placebo
      controlled trial].
AB  - OBJECTIVE: To evaluate the efficacy and safety of bicyclum, a China made new
      hepatocyte protecting agent, in the treatment of chronic hepatitis C (CHC).
      METHODS: Thirty-nine CHC patients matched demographically and clinically were
      randomized into two groups: bicyclum group (group A, n = 20) and placebo/bicyclum
      crossovergroup (group B, n = 19). Bicyclum 75mg/d or placebo was administered to
      these two groups respectively for 3 months. Then the patients in group A received
      bicyclum for further 3 months and were observed for 3 months after the treatment
      discontinued; and the patients in group B received bicyclum 75mg/d for six months
      and were observed for 3 months after the treatment discontinued. Investigation
      items included clinical manifestations,liver function, serum HCV RNA and anti
      HCV. RESULTS: In group A, the serum ALT was 120 +/- 43 U/L before treatment and
      was 57 +/- 32 U/L after treatment ( P < 0.01) In group B the baseline serum ALT
      was 126 U/L +/- 48 U/L. After the placebo administration the serum ALT was 127
      U/L +/- 97 U/L (P > 0.05) and the clinical feature showed no improvement. After
      bicyclum treatment for 6 months, the serum ALT in group B was 68 +/- 45 U/L,
      significantly lower than that before bicyclum treatment ( P < 0.01) and clinical
      symptoms improved. The overall ALT normalization response rate were 64.1% and
      48.7% at the end of bicyclum treatment and 3 months after the treatment
      discontinued respectively for the total 39 patients. The serum HCV-RNA became
      negative in 5 and 2 patients at end of treatment and 3 months after the treatment
      discontinued. Adverse drug reactions were mild and uncommon. Mild dizziness
      occurred in 1 patient in each group. CONCLUSION: Bicyclum is effective in
      improving ALT and clinical manifestations of CHC patients. It is safe and well
      tolerated and shows few adverse reactions.

PMID- 12181090
TI  - [Effect of GrB- positive expression in benign and malignant gastric epithelial
      tissue on local immune response].
AB  - OBJECTIVE: To observe whether benign and malignant gastric epithelial cells
      express cytotoxic protein GrB and investigate its effect on local immune
      response. METHODS: Immunohistochemical staining for GrB was performed on paraffin
      sections from 8 specimens of chronic superficial gastritis (CSG) and 35 specimens
      of gastric cancer (GC) to detect the GrB expression and density of infiltration
      by GrB(+)cytotoxic lymphocyte (CTL) and NK. RESULTS: (1) GrB was expressed in
      both benign and malignant gastric epithelial cells with the expression rates of
      62.5% (5/8) and 40% (14/35) respectively (kappa(2) = 0.58, P > 0.05). (2) The
      density of infiltration by GrB(+) CTL and NK in GC group was greater than that in
      CSG group, however without significant difference (t = 1.628, P > 0.05). (3) The
      density of infiltration by GrB(+) CTL and NK, and GrB expression in GC showed no
      significant difference among different clinicopathological variables except age.
      The GrB expression rate in age group impended to the marked level of test (P =
      0.06). (4) The density of infiltration by GrB(+) CTL and NK in GrB-positive GC
      group was significantly less than that in GrB-negative GC group (t = 1.89, P <
      0.05). The density of infiltration by GrB(+) CTL and NK showed a significantly
      negative correlation with GrB expression in GC (gamma(s) = -0.55, P < 0.001).
      CONCLUSION: GrB expression in gastric epithelial cell may be one of the
      accompanying changes in the course of malignant transformation of cells and play
      an important role in inhibiting local immune response, and it can be speculated
      as a novel molecule mechanism for tumor to escape immune surveillance.

PMID- 12181091
TI  - [Expression of osteopontin mRNA and its protein in colorectal cancer and liver
      metastatic tissues].
AB  - OBJECTIVE: To investigate the expression of osteopontine (OPN) in colorectal
      cancer and liver metastatic tissues and the significance of OPN in tumorigenesis
      and liver metastasis of colorectal cancer. METHODS: The expression of OPN mRNA in
      44 samples of colorectal cancer tissues and adjacent normal tissues and 20
      samples of liver metastatic tissues was examined by FQ-PCR, using glyceraldehyde
      3-phosphate dehydrogenase (GAPDH) as internal standard. S-P immunohistochemical
      method was utilized to detect the OPN protein in colorectal cancer and liver
      metastasis tissues. On the principle that the C(T) value is in inverse proportion
      to the log value of original copy number of target sequence, OPN C(T)/GAPDH C(T)
      was used to evaluate the mRNA expression level in different tissues. RESULTS: The
      OPN mRNA levels in colorectal cancer tissues were 0.85 approximately 1.47 (kappa
      +/- s = 1.15 +/- 0.14 ), significantly higher than those in adjacent normal
      tissues (0.94 approximately 1.47,kappa +/- s =1.32 +/- 0.18) and lower than those
      in liver metastatic tissues (0.92 approximately 1.30,kappa +/- s =1.07 +/- 0.10)
      (t =5.81, P =0.00 and t = 2.12,P =0.038), Immunohistochemistry showed that OPN
      protein was localized in the cytoplasm of colorectal cancer cells, metastatic
      cancer cells, and normal hepatocytes around metastatic tissue, but not in the
      normal colorectal tissues around the primary cancer and normal hepatocytes in
      persons without colorectal cancer. CONCLUSION: The expression of OPN mRNA is the
      highest in liver metastatic tissues, moderate in primary colorectal cancer
      tissues, and lowest in adjacent normal tissues of the metastatic liver cancer.
      OPN protein is located in cytoplasm of colorectal cancer cells. OPN is a
      potential marker for liver metastasis of colorectal cancer.

PMID- 12181092
TI  - [Expression and relocation of B23 in the process of rat liver cell hyperplasia
      and liver regeneration].
AB  - OBJECTIVE: To study the B23 expression and relocation in the process of liver
      regeneration at different time periods after partial hepatectomy (PH) on healthy
      rats, and to study the feasibility of using B23 as a proliferation marker.
      METHODS: Eighteen rats underwent partial hepatectomy (PH). The regenerative liver
      tissues were obtained at day 1, 2, 3, 4,and 7 after PH. The expression of B23 in
      hepatocytes of the regenerative tissues was measured using monoclonal antibody
      against nucleophosmin/B23 by Western blot and immunohistochemistry. The
      expression of proliferate cell nuclear antigen (PCNA) in these cells were
      measured using monoclonal antibody against PCNA by both methods for comparison
      with that of B23. RESULTS: Expression of B23 in the steady state of liver cells
      before PH was hardly detected by both methods. The increased expression of B23 in
      the regenerative liver cells was quantitatively changed like a parabolic curve at
      day 1 to days 7 after PH, with the peak expression of B23 at day 3 after PH. This
      quantitative variation of B23 expression was similar to that of PCNA expression.
      The variation of location of B23 in the regenerative liver cells was observed
      from nucleolus (G1-S phase) to nucleoplasm (S-G2 phase) and to cytoplasm and
      mitotic chromosome (M phase). CONCLUSION: B23 expression is quantitatively
      increased and moves in location in the process of liver regeneration after PH.
      B23 may be regarded as a proliferation marker in liver regeneration and liver
      cell hyperplasia.

PMID- 12181093
TI  - [Central nervous system infection complicated after cardiac surgery, a clinical
      analysis of 10 173 cases].
AB  - OBJECTIVE: To assess the morbidity, mortality, clinical features, death causes,
      prevention and treatment of patients with central nervous system infection(CNSI)
      undergoing cardiopulmonary bypass (CPB) surgery. METHODS: 10 173 cases of CNSI
      undergoing CPB surgery 1984 approximately 1997 were reviewed retrospectively to
      analysed the morbidity, mortality, clinical features, death causes, prevention
      and treatment of patients with CNSI after CPB surgery. RESULTS: After CPB
      surgery, the general morbidity of neurological complications (NC) was 1.4%
      (146/10 173), of which cerebrovascular diseases accounted for 59.6% (87/146), and
      CNSI 7.53%(11/146). The aortic clump time and CPB time were significantly longer
      in the CNSI group than in the controls (P < 0.01). Death occurred in 44 patients
      of the NC group, in which CNSI accounted for 18.2%(8/44). CONCLUSION:
      Postoperative CNSI correlates with longer aortic clump time and CPB time during
      the operation, and high mortality in CNSI group.

PMID- 12181094
TI  - [Complete genome sequence of 84FLi, a Hantaan virus strain isolated from the
      liver of fetus aborted by a pregnant women with hemmorrhagic fever with renal
      syndrome].
AB  - OBJECTIVE: To study the complete genome sequence of the Chinese Hantaan virus
      vaccine strain 84FLi and learn about its molecular characters. METHODS: The virus
      strain 84FLi was isolated from the liver of a fetus aborted by pregnant women
      with hemorrhagic fever with renal syndrome. The cDNAs of L  M and S segments were
      amplified fragment by fragment using RT-PCR. The purified PCR products were
      sequenced directly or cloned into pMD18-T vector and then sequenced. RESULTS: The
      complete genome of strain 84FLi was composed of L ( 6 533 bp)   M (3 616 bp) and
      S (1 688 bp)  coding 2151  1135 and 429 amino acids  respectively. The entire
      sequence composition was 3830A  2050C  2510G and 3447T  the GC and AT contents
      were 38.52% and 61.48%. Homology analysis showed that the homologies of 84 FLi S
      segment nucleotide sequences with strain RG9 (isolated in Guangzhou) and strain
      Chen4 (isolated in Anhui) were 99.6%. There were 83.7%  84.0% and 87.2%
      nucleotide sequences homology with the three segments of Hantaan virus foreign
      standard strain  76-118   while the amino acids sequences homology with those of
      76-118 were 97.5%  96.0% and 97.9% respectively. CONCLUSION: The strain 84FLi is
      highly related to other Chinese Hantaan virus isolates and is in the same subtype
      with the other two Chinese isolates RG9 and Chen4.

PMID- 12181095
TI  - [Experimental study of multidrug resistance mediated by human laminin receptor in
      gastric cancer cells].
AB  - OBJECTIVE: To study the mechanisms of multidrug resistance (MDR) mediated by
      human 67 000 laminin receptor (LR) with a relative molecular mas of 67 000 in
      gastric cancer cells. METHODS: Antisense RNA expression vector corresponding to
      LR precursor (LRP) was constructed by DNA recombinant technique, and transferred
      into gastric cancer MDR cells SGC7901/VCR with Lipofect AMINE. Western blot was
      employed to determine the LR expression level in gastric cancer cells. The
      sensitivity of gastric cancer cells to chemotherapeutic drugs was evaluated with
      MTT assay. Flow cytometry was used to analyze the cell cycle and to assess the
      mean fluorescence intensity of intracellular adriamycin in gastric cancer cells.
      RESULTS: Western blotting analysis demonstrated a decreased expression level of
      LR in SGC7901/VCR cells transfected with LRP antisense RNA expression vector. In
      comparison with the gastric cancer cells with out transfection or transfected
      with invalid vector, LR down-regulated transfectants (SGC7901/VCR-anLRP) showed
      higher sensitivity to vincristine, adriamycin, 5-fluodrouracil and cisplatin, and
      increased accumulation and retention of adriamycin. Cell cycle analysis suggested
      G1 block and spontaneous apoptosis of SGC7901/VCR-anLRP cells. CONCLUSION: LR
      might take part in mediation of MDR in gastric cancer cells through interfering
      with drug accumulation and cell apoptosis.

PMID- 12181096
TI  - [Effect of interleukin  I receptor antigonist gene therapy on arthritis induced
      by type II collagen in mice].
AB  - OBJECTIVE: To investigate the effect of interleukin-1 receptor antagonist gene
      therapy on type II collagen induced arthritis in DBA/1 mice. METHODS: Plasmid
      pcDI-IL-1ra that expresses IL-1ra in eukaryotes was constructed by inserting
      human IL-1ra cDNA into the eukaryotic expression vector pcDI. Eukaryotes were
      transfected with the plasmid pcDI-IL-1ra in vivo and in vitro. The expression of
      8 IL-1ra was examined by ELISA and immunohistochemistry. Type II collagen was
      used to induced arthritis in 32 DBA/1 mice. This plasmid was injected into the
      muscles of DBA/1 mice with arthritis induced by type II collagen by gene gun (20
      micro g/mouse) and into the muscle of 8 mice by intramuscular injection (200
      micro g/mouse). After the administration, the condition of arthritis was
      observed. The serum IL-ira was examined 6 and 12 days after administration. The
      expression of IL-ira in muscles was tested by computerized imaging analysis.
      RESULTS: PCR and DNA sequencing proved the accuracy of the inserted fragment.
      ELISA and immunohistochemistry detected high expression of IL-ira in vivo and in
      vitro. The absorbance ( A ) 490 value of IL-ira in the mouse muscle was 0.52 +/-
      0.03 in gene gun group, and 0.48 +/- 0.02 in intramuscular injection group, all
      higher than that in the control group (0.41 +/- 0.02,P < 0.01 and P < 0.05). The
      serum IL-ira values in the gene gun group and in tramuscular injection group 6
      days and 12 days after therapy were all significantly higher than that in the
      control group (all P < 0.01; and P < 0.01 and P < 0.05). Since the 6 th day after
      therapy, the redness and swelling of joints in both therapies groups were
      alleviated. Pathological examination made 12 days after therapy showed relief at
      different degrees of the infiltration of inflammatory cells, hyperplasia of
      synovia, bone infiltration, and cartilage destruction, especially in the gene gun
      group. CONCLUSION: Gene therapy of IL-ira via non-virus eukaryotic expression
      vactor, especially by gene gun, is effective in treating arthritis induced by
      type II collagen.

PMID- 12181098
TI  - Commentary: epidemiology and the continuum from genetic research to genetic
      testing.

PMID- 12181099
TI  - Reporting, appraising, and integrating data on genotype prevalence and gene
      disease associations.
AB  - The recent completion of the first draft of the human genome sequence and
      advances in technologies for genomic analysis are generating tremendous
      opportunities for epidemiologic studies to evaluate the role of genetic variants
      in human disease. Many methodological issues apply to the investigation of
      variation in the frequency of allelic variants of human genes, of the possibility
      that these influence disease risk, and of assessment of the magnitude of the
      associated risk. Based on a Human Genome Epidemiology workshop, a checklist for
      reporting and appraising studies of genotype prevalence and studies of gene
      disease associations was developed. This focuses on selection of study subjects,
      analytic validity of genotyping, population stratification, and statistical
      issues. Use of the checklist should facilitate the integration of evidence from
      these studies. The relation between the checklist and grading schemes that have
      been proposed for the evaluation of observational studies is discussed. Although
      the limitations of grading schemes are recognized, a robust approach is proposed.
      Other issues in the synthesis of evidence that are particularly relevant to
      studies of genotype prevalence and gene-disease association are discussed,
      notably identification of studies, publication bias, criteria for causal
      inference, and the appropriateness of quantitative synthesis.

PMID- 12181100
TI  - Genetic test evaluation: information needs of clinicians, policy makers, and the
      public.
AB  - Growing knowledge about gene-disease associations will lead to new opportunities
      for genetic testing. Many experts predict that genetic testing will become
      increasingly important as a guide to prevention, clinical management, and drug
      treatment based on genetic susceptibilities. As part of a Human Genetic
      Epidemiology workshop convened by the Centers for Disease Control and Prevention,
      a group of experts evaluated the evidence needed when considering the appropriate
      use of new genetic tests. Because new tests are likely to vary in their
      predictive value, their potential to direct prevention or treatment efforts, and
      their personal and social consequences, the task of determining appropriate use
      will require careful consideration of a variety of factors, including the
      analytic validity, clinical validity, clinical utility, and ethical, legal, and
      social implications of the test. Standardized formats are needed to summarize
      what is known and not known about new genetic tests with respect to each of these
      features. Following criteria for the objective assessment of test properties,
      reports should be structured to enable policy makers, clinicians, and the public
      to identify the available evidence, so that uncertainties can be taken into
      account when considering test use and planning future research.

PMID- 12181101
TI  - Cannabis use and psychosis: a longitudinal population-based study.
AB  - Cannabis use may increase the risk of psychotic disorders and result in a poor
      prognosis for those with an established vulnerability to psychosis. A 3-year
      follow-up (1997-1999) is reported of a general population of 4,045 psychosis-free
      persons and of 59 subjects in the Netherlands with a baseline diagnosis of
      psychotic disorder. Substance use was assessed at baseline, 1-year follow-up, and
      3-year follow-up. Baseline cannabis use predicted the presence at follow-up of
      any level of psychotic symptoms (adjusted odds ratio (OR) = 2.76, 95% confidence
      interval (CI): 1.18, 6.47), as well as a severe level of psychotic symptoms (OR =
      24.17, 95% CI: 5.44, 107.46), and clinician assessment of the need for care for
      psychotic symptoms (OR = 12.01, 95% CI: 2.24, 64.34). The effect of baseline
      cannabis use was stronger than the effect at 1-year and 3-year follow-up, and
      more than 50% of the psychosis diagnoses could be attributed to cannabis use. On
      the additive scale, the effect of cannabis use was much stronger in those with a
      baseline diagnosis of psychotic disorder (risk difference, 54.7%) than in those
      without (risk difference, 2.2%; p for interaction = 0.001). Results confirm
      previous suggestions that cannabis use increases the risk of both the incidence
      of psychosis in psychosis-free persons and a poor prognosis for those with an
      established vulnerability to psychotic disorder.

PMID- 12181102
TI  - Physical activity reduces the risk of subsequent depression for older adults.
AB  - Previous studies assessing protective effects of physical activity on depression
      have had conflicting results; one recent study argued that excluding disabled
      subjects attenuated any observed effects. The authors' objective was to compare
      the effects of higher levels of physical activity on prevalent and incident
      depression with and without exclusion of disabled subjects. Participants were
      1,947 community-dwelling adults from the Alameda County Study aged 50-94 years at
      baseline in 1994 with 5 years of follow-up. Depression was measured using
      criteria from the Diagnostic and Statistical Manual of Mental Disorders, Fourth
      Edition (Washington, DC: American Psychiatric Association, 1994). Physical
      activity was measured with an eight-point scale; odds ratios are based upon a one
      point increase on the scale. Even with adjustments for age, sex, ethnicity,
      financial strain, chronic conditions, disability, body mass index, alcohol
      consumption, smoking, and social relations, greater physical activity was
      protective for both prevalent depression (adjusted odds ratio (OR) = 0.90, 95%
      confidence interval (CI): 0.79, 1.01) and incident depression (adjusted OR =
      0.83, 95% CI: 0.73, 0.96) over 5 years. Exclusion of disabled subjects did not
      attenuate the incidence results (adjusted OR = 0.79, 95% CI: 0.67, 0.92).
      Findings support the protective effects of physical activity on depression for
      older adults and argue against excluding disabled subjects from similar studies.

PMID- 12181103
TI  - Correlates of bone and blood lead levels among middle-aged and elderly women.
AB  - In 1993-1995, the authors evaluated risk factors for elevated blood and bone lead
      levels in 264 Boston, Massachusetts, area women previously selected for a case
      control study of lead and hypertension. Bone lead was measured at the tibia and
      patella with K x-ray fluorescence. Blood lead was analyzed by graphite furnace
      atomic absorption. Participants were aged 46-74 years and had mean lead levels of
      3 (standard deviation, 2) micro g/dl (blood), 13 (standard deviation, 9) micro
      g/g (tibia), and 17 (standard deviation, 11) micro g/g (patella). In multivariate
      linear regression models, use of postmenopausal estrogen (inverse) and alcohol
      intake (positive) were significantly associated with blood lead levels. Both bone
      lead measures were significantly and positively associated with blood lead but
      only among postmenopausal women not using estrogen; for example, an increase from
      the first to the fifth quintile of tibia lead level (19 micro g/g) was associated
      with a 1.7- micro g/dl increase in blood lead (p = 0.0001) in this group. Older
      age and lower parity were associated with higher tibia lead; only age was
      associated with patella lead. The observed interaction of bone lead with estrogen
      status in determining blood lead supports the hypothesis that increased bone
      resorption, as occurs postmenopausally because of decreased estrogen production,
      results in heightened release of bone lead stores into blood.

PMID- 12181104
TI  - Anthropometric and behavioral correlates of insulin-like growth factor I and
      insulin-like growth factor binding protein 3 in middle-aged Japanese men.
AB  - High levels of plasma insulin-like growth factor I (IGF-I) and low levels of
      insulin-like growth factor binding protein 3 (IGFBP-3) have been related to
      increased risk of several cancers. Little is known about the behavioral
      determinants of these biologic markers. The authors examined the relation of
      anthropometric and behavioral factors to plasma concentrations of IGF-I and IGFBP
      3 in a cross-sectional study of 616 Japanese men aged 45-55 years in 1995-1996.
      In univariate analyses, body mass index was strongly, positively associated with
      both IGF-I and IGFBP-3. The waist/hip ratio was also linearly related to IGF-I
      and IGFBP-3 up to the third quartile level. Height was weakly, positively
      associated with IGF-I and IGFBP-3. Smoking was inversely associated with IGF-I
      and IGFBP-3. Alcohol use was associated inversely with IGF-I and positively with
      IGFBP-3. Neither IGF-I nor IGFBP-3 was related to physical activity. Results of
      the multivariate analysis were essentially the same as those of the univariate
      analyses. The findings regarding body mass index are in contrast to those of
      previous studies showing null or inverse associations, and they suggest that the
      relation of body mass index to IGF-I or IGFBP-3 may vary among populations. The
      study also indicates that smoking and alcohol use might affect plasma IGF-I and
      IGFBP-3.

PMID- 12181105
TI  - Serum insulin and glucose levels and breast cancer incidence: the atherosclerosis
      risk in communities study.
AB  - The authors examined the association of breast cancer incidence with serum levels
      of insulin and glucose in a cohort of 7,894 women aged 45-64 years from four US
      communities. Anthropometric factors and fasting levels of insulin and glucose
      were measured at baseline (1987-1989). Over an average follow-up period of 7.1
      years (1987-1995), 187 breast cancer cases were ascertained. Breast cancer was
      associated positively with body mass index but not with waist:hip ratio or serum
      insulin level. After adjustment for age, race, and study site, the incidence of
      breast cancer was 60% higher among diabetic women than among women with fasting
      glucose levels under 100 mg/dl, but this association was attenuated after further
      adjustment for body mass index and other covariates (adjusted rate ratio = 1.39,
      95% confidence interval: 0.86, 2.23). Circulating insulin levels were not
      predictive of future breast cancer incidence, but there may be a weak association
      with type 2 diabetes, perhaps modulated via increased adiposity.

PMID- 12181106
TI  - Instrumental measurements of skin color and skin ultraviolet light sensitivity
      and risk of cutaneous malignant melanoma: a case-control study in an Italian
      population.
AB  - The authors evaluated objective measurements of constitutive skin color and
      ultraviolet light sensitivity in relation to risk of cutaneous malignant melanoma
      (CMM). Incident CMM cases (n = 183) were diagnosed between December 1994 and
      January 1999 at the Maurizio Bufalini Hospital in Cesena, Italy. Controls (n =
      179) were mostly spouses/partners of cases and were frequency-matched by age and
      sex. In addition to interviews, constitutive skin color and skin ultraviolet
      light sensitivity were assessed by colorimetry and minimal erythema dose (MED),
      respectively. Odds ratios were estimated using unconditional logistic regression.
      The odds of CMM increased by a factor of 1.20 (95 percent confidence interval:
      1.12, 1.30) for each unit of skin brightness and by a factor of 1.24 (95 percent
      confidence interval: 1.07, 1.43) per 10 mJ/cm(2) of MED. These associations were
      largely independent of phenotypic or sun-related characteristics and were
      modified by sun exposure. Increased risk of CMM was observed only among subjects
      with the highest levels of sun exposure. Epidemiologic studies of CMM may benefit
      from the inclusion of colorimetric and MED measurements along with traditional
      risk factors to obtain more accurate, quantitative, and objective information.

PMID- 12181107
TI  - Risk factors for invasive epithelial ovarian cancer: results from a Swedish case
      control study.
AB  - This case-control study evaluated reproductive and other factors in relation to
      epithelial ovarian cancer (EOC) risk. Between 1993 and 1995, the authors
      recruited 655 EOC cases and 3,899 population controls aged 50-74 years who were
      born in and residents of Sweden. Data were collected through mailed
      questionnaires. Odds ratios were estimated by unconditional logistic regression.
      Parity reduced EOC risk (odds ratio = 0.61, 95% confidence interval (CI): 0.46,
      0.81) for uniparous compared with nulliparous women. The risk of EOC decreased
      with incomplete pregnancies, early menopausal age, late age at first birth, and
      unilateral oophorectomy; increased with family history of ovarian cancer; and was
      not associated with menarcheal age, lactation, irregular menses, and menopausal
      symptoms. Histology-specific odds ratios of EOC for ever compared with never
      users of oral contraceptives were: serous, 0.56 (95% CI: 0.42, 0.74); mucinous,
      1.96 (95% CI: 1.04, 3.68); endometrioid, 0.71 (95% CI: 0.49, 1.03); clear cell,
      0.66 (95% CI: 0.31, 1.43); and all EOCs, 0.73 (95% CI: 0.59, 0.90). Prolonged
      oral contraceptive use reduced EOC risk, with persistent protection up to 25
      years after the last use. Ever use of hormone replacement therapy increased EOC
      risk (odds ratio = 1.41, 95% CI: 1.15, 1.72). Among etiologic hypotheses, the
      retrograde transportation hypothesis accommodates most epidemiologic findings
      concerning EOC risk.

PMID- 12181108
TI  - Risk of specific birth defects in relation to chlorination and the amount of
      natural organic matter in the water supply.
AB  - To assess the effect of water chlorination by-products on specific birth defects,
      the authors conducted a nationwide cross-sectional study of 285,631 Norwegian
      births in 1993-1998. Risks of birth defects according to four chlorination by
      product exposure categories were compared on the basis of chlorination (yes/no)
      and level of water color (mg Pt/liter), representing the amount of natural
      organic matter: high (chlorination, < or =20), medium (chlorination, 10-19.9),
      and low (chlorination, <10) exposure, with no chlorination and low color (<10) as
      the reference category. In logistic regression analysis, the risks of any birth
      defect (adjusted odds ratio (OR) = 1.13, 95% confidence interval (CI): 1.01,
      1.25) and of cardiac (adjusted OR = 1.37, 95% CI: 1.00, 1.89), respiratory system
      (adjusted OR = 1.89, 95% CI: 1.00, 3.58), and urinary tract (adjusted OR = 1.46,
      95% CI: 1.00, 2.13) defects were significantly associated with exposure (medium
      and high combined). Regarding risk of specific birth defects, only that for
      ventricular septal defects was significantly elevated, with an exposure-response
      pattern, yielding adjusted odds ratios of 1.63 (95% CI: 1.02, 2.58) for the
      medium and 1.81 (95% CI: 1.05, 3.09) for the high exposure categories.
      Furthermore, risk of neural tube defects was related to high color (adjusted OR =
      2.60, 95% CI: 1.30, 5.26).

PMID- 12181109
TI  - Serum dioxin concentrations and menstrual cycle characteristics.
AB  - 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is a widespread industrial
      environmental contaminant. Animal studies suggest that TCDD exposure alters the
      estrus cycle. Twenty years after a 1976 industrial explosion in Seveso, Italy,
      the authors interviewed female residents to determine whether there was an
      association between TCDD exposure and current menstrual cycle characteristics.
      The authors analyzed serum samples collected soon after the explosion to quantify
      individual TCDD levels. Among women who were premenarcheal at the time of the
      explosion, a 10-fold increase in serum TCDD level was associated with a
      lengthening of the menstrual cycle by 0.93 days (95% confidence interval (CI): 
      0.01, 1.86) and a reduction in the odds of scanty menstrual flow (adjusted odds
      ratio = 0.33, 95% CI: 0.10, 1.06). However, among women who were postmenarcheal
      at the time of the explosion, TCDD was not associated with menstrual cycle length
      (adjusted beta = -0.03 days, 95% CI: -0.61, 0.54) or scantiness of flow (adjusted
      odds ratio = 1.36, 95% CI: 0.70, 2.64). In both menarche groups, TCDD levels were
      associated with decreased odds of having irregular cycles (adjusted odds ratio =
      0.46, 95% CI: 0.23, 0.95) but were not related to days of flow (adjusted beta =
      0.16 days, 95% CI: -0.08, 0.41). These results are consistent with effects of
      TCDD on ovarian function noted in some animal species and with greater
      sensitivity to TCDD during development.

PMID- 12181111
TI  - Ovariectomy increases mitogens and platelet-induced proliferation of arterial
      smooth muscle.
AB  - Experiments were designed to determine how ovariectomy modulates mitogenic
      factors in platelets and how these factors affect proliferation of coronary
      arterial smooth muscle. Platelet-derived growth factors (PDGF(AB) and PDGF(BB)),
      transforming growth factors (TGF-beta(1) and TGF-beta(2)), and vascular
      endothelial growth factor (VEGF(165)) were quantified in platelet lysates and
      platelet-poor plasma from adult gonadally intact and ovariectomized female pigs
      by ELISA. Proliferation of cultured coronary arterial smooth muscle cells (SMCs)
      from both groups of pigs was determined in response to autologous or heterologous
      platelet lysates. Platelet concentrations of PDGF(BB), but not PDGF(AB), TGF
      beta(1), and TGF-beta(2), increased with ovariectomy. VEGF(165) was not detected
      in platelets from either group. Proliferation of SMCs from ovariectomized females
      was significantly greater on exposure to autologous or heterologous platelet
      lysates than proliferation of SMCs from intact females. These results indicate
      that ovariectomy increases concentrations of PDGF(BB) in platelets. Higher levels
      of PDGF(BB) in platelets in synergy with other platelet-derived products could
      contribute to increased proliferative arterial response to injury after
      ovariectomy.

PMID- 12181110
TI  - Effect of gender on endothelium-dependent dilation to bradykinin in human adipose
      microvessels.
AB  - We examined the influence of gender and climacteric status, two coronary risk
      factors, on bradykinin (BK)-induced dilation in adipose arterioles from men and
      women of different ages [premenopausal women (Pre-W), postmenopausal women (Post
      W), and similar aged men (Y-M and O-M), respectively]. We examined the responses
      from both omental (more closely associated with coronary disease) and
      subcutaneous fat. Tissues were obtained at surgery and cannulated (60 mmHg) for
      measurement of internal diameter. In vessels from omental tissue, dilation to BK
      was more sensitive in Pre-W than other groups, whereas in vessels from
      subcutaneous tissue, sensitivity to BK was greater in both Pre-W and Post-W
      compared with Y-M and O-M. Maximal dilation was similar among groups.
      Indomethacin (Indo; 10(-5) M) alone had no effect on dilation to BK in any
      groups, but Indo and N(omega)-nitro-L-arginine methyl ester (L-NAME; 10(-4) M)
      reduced dilation to BK in Pre-W more than in Y-M. L-NAME increased dilation to BK
      in subcutaneous fat from Y-M but had no effect in Post-W and O-M. Indo- and L
      NAME-resistant dilation in all vessels was markedly reduced by 30 mM KCl. There
      was no difference in sodium nitroprusside-induced dilation among groups. We
      conclude that gender and climacteric state contribute to mechanisms of
      microvascular regulation in humans. Functional vascular differences in visceral
      and subcutaneous fat may underlie the proposed differential influence of these
      tissues on cardiovascular risk.

PMID- 12181112
TI  - Stabilization of mast cells by heme oxygenase-1: an anti-inflammatory role.
AB  - This study examined the role of bilirubin in heme oxygenase (HO)-1-mediated
      amelioration of mast cell (MC)-elicited inflammatory responses. Pretreatment of
      rats with an intraperitoneal injection of hemin, an inducer of HO-1, evolved a
      marked induction of the enzyme in MCs. Intravital videomicroscopy revealed that
      hemin pretreatment attenuated compound 48/80-elicited degranulation of MCs and
      resultant leukocyte adhesion in venules. Superfusion with biliverdin or
      bilirubin, but not with carbon monoxide (CO), another product of the HO reaction,
      mimicked suppressive actions of the HO-1 induction on both the cell degranulation
      and leukocyte adhesion elicited by the stimulus, suggesting a requirement of the
      enzyme reaction to generate bilirubin in the inhibitory mechanisms. Such MC
      desensitizing actions of bilirubin were observed in primary-cultured MCs and
      reproduced irrespective of the choice of stimuli, such as compound 48/80, calcium
      ionophore, and anti-IgE serum. Furthermore, MC-stabilizing effects of HO-1 were
      reproduced by the gene transfection of the enzyme into mastocytoma cell line
      RBL2H3. These results suggest that bilirubin generated through HO-1 serves as an
      anti-inflammatory substance that desensitizes MCs and ameliorates leukocyte
      recruitment.

PMID- 12181113
TI  - Mitochondrial respiratory control can compensate for intracellular O(2) gradients
      in cardiomyocytes at low PO(2).
AB  - In isolated single cardiomyocytes with moderately elevated mitochondrial
      respiration, direct evidence for intracellular radial gradients of oxygen
      concentration was obtained by subcellular spectrophotometry of myoglobin (Mb).
      When oxygen consumption was increased by carbonyl cyanide m-chlorophenylhydrazone
      (CCCP) during superfusion of cells with 4% oxygen, PO(2) at the cell core dropped
      to 2.3 mmHg, whereas Mb near the plasma membrane was almost fully saturated with
      oxygen. Subcellular NADH fluorometry demonstrated corresponding intracellular
      heterogeneities of NADH, indicating suppression of mitochondrial oxidative
      metabolism due to relatively slow intracellular oxygen diffusion. When oxygen
      consumption was increased by electrical pacing in 2% oxygen, radial oxygen
      gradients of similar magnitude were demonstrated (cell core PO(2) = 2.6 mmHg).
      However, an increase in NADH fluorescence at the cell core was not detected.
      Because CCCP abolished mitochondrial respiratory control while it was intact in
      electrically paced cardiomyocytes, we conclude that mitochondria with intact
      respiratory control can sustain electron transfer with reduced oxygen supply.
      Thus mitochondrial intrinsic regulation can compensate for relatively slow oxygen
      diffusion within cardiomyocytes.

PMID- 12181114
TI  - The effect of interleukin-6 on L-selectin levels on polymorphonuclear leukocytes.
AB  - Interleukin-6 (IL-6) shortens the transit time of polymorphonuclear leukocytes
      (PMN) through the marrow and accelerates their release into the circulation. In
      contrast to other inflammatory stimuli, this response is associated with a
      decrease in L-selectin levels on circulating PMN. The present study was designed
      to determine the effect of IL-6 on L-selectin levels of PMN in rabbits.
      Recombinant human IL-6 (2 microg/kg) caused a decrease in L-selectin levels on
      circulating PMN 3 to 12 h after treatment (P < 0.05). L-selectin levels decreased
      on PMN already in the circulation for up to 4 h (P < 0.05), on PMN released from
      the marrow posttreatment for up to 12 h (P < 0.01) and on PMN in the marrow for
      up to 6 h (P < 0.05) after IL-6 treatment. We conclude that IL-6 decreases L
      selectin levels on circulating PMN by demarginating PMN with low levels of L
      selectin and by releasing PMN from the marrow with low levels of L-selectin. We
      postulate that this prolonged downregulation of L-selectin on circulating PMN
      could influence their recruitment into inflammatory sites.

PMID- 12181115
TI  - Nitric oxide-independent effects of tempol on sympathetic nerve activity and
      blood pressure in DOCA-salt rats.
AB  - The role of sympathetic nerves and nitric oxide (NO) in tempol-induced
      cardiovascular responses was evaluated in urethane-anesthetized sham and
      deoxycorticosterone acetate (DOCA)-salt-treated (DOCA-salt) rats. Tempol (30-300
      micromol/kg iv), a superoxide (O) scavenger, decreased renal sympathetic nerve
      activity (RSNA), mean arterial pressure (MAP), and heart rate (HR) in DOCA-salt
      and sham rats. The antioxidants tiron and ascorbate did not alter MAP, HR, or
      RSNA in any rat. Tempol responses were unaffected after sham rats were treated
      with N(G)-nitro-L-arginine (L-NNA, 13 mg/kg). In DOCA-salt rats, L-NNA reduced
      tempol-induced depressor responses but not the inhibition of HR or RSNA. Tempol
      did not significantly decrease MAP, HR, or RSNA after hexamethonium (30 mg/kg iv)
      treatment in any rat. Dihydroethidine histochemistry revealed increased O levels
      in arteries and veins from DOCA-salt rats. Tempol treatment in vitro reduced O
      levels in arteries and veins from DOCA-salt rats. In conclusion, tempol-induced
      depressor responses are mediated largely by NO-independent sympathoinhibition in
      sham and DOCA-salt rats. There is an additional interaction between NO and tempol
      that contributes to depressor responses in DOCA-salt rats.

PMID- 12181116
TI  - Estrogen replacement reduces PGHS-2-dependent vasoconstriction in the aged rat.
AB  - The reduction in estrogen in postmenopausal women contributes to an increase in
      vascular dysfunction. Models of aging have shown that this is due, in part, to
      increased prostaglandin H synthase (PGHS)-dependent vasoconstriction. We showed
      previously that inducible PGHS-2-dependent vasoconstriction is increased with
      aging. In the present study, we hypothesized that estrogen suppresses PGHS-2
      dependent constriction in the aged rat. Isolated mesenteric arteries from placebo
      or estrogen-treated, ovariectomized aged (24 mo) Fisher rats were assessed for
      endothelium-dependent relaxation in the absence or presence of PGHS inhibitors.
      PGHS inhibition (meclofenamate, 1 micromol/l) enhanced methacholine-induced
      relaxation only in the placebo group. Specific PGHS-2 inhibition (NS-398, 10
      micromol/l) increased arterial relaxation to a greater extent than PGHS-1
      inhibition (valeryl salicylate, 3 mmol/l). Estrogen prevented the PGHS-dependent
      constrictor effect but did not enhance nitric oxide-dependent relaxation in this
      model. PGHS-1 and endothelial nitric oxide synthase were not altered by estrogen,
      whereas PGHS-2 expression was decreased in the estrogen-replaced rats (P < 0.05).
      In summary, estrogen replacement improved vasodilation in aged rats by decreasing
      PGHS-dependent constriction.

PMID- 12181117
TI  - Effect of lower limb exercise on forearm vascular function: contribution of
      nitric oxide.
AB  - We examined vascular function in an inactive muscle bed, the forearm, during
      lower limb exercise and determined the contribution of endothelium-derived nitric
      oxide (NO) to the hyperemic response. Eight young males were randomized to
      participate in two studies, each consisting of two bouts of lower limb exercise,
      separated by a 30-min recovery. Peak forearm blood flow (PFBF) and mean blood
      flow (MFBF) were continuously recorded at baseline and during exercise using
      continuous high-resolution vascular ultrasound and Doppler flow velocity
      measurement. During one session, the brachial artery was cannulated to allow
      continuous infusion of saline or N(G)-monomethyl-L-arginine (L-NMMA), an
      inhibitor of NO synthase. The alternate session was performed to control for
      possible effects of repeated exercise. At 60, 100, and 160 W, L-NMMA
      significantly decreased both PFBF and MFBF compared with the saline infusion.
      These results suggest that systemic production of NO occurs during exercise in
      resting vessel beds, which do not feed metabolically active tissue. This finding
      provides a plausible explanation for the antiatherogenic benefits of exercise.

PMID- 12181118
TI  - Spatial velocity profile in mouse embryonic aorta and Doppler-derived volumetric
      flow: a preliminary model.
AB  - Characterizing embryonic circulatory physiology requires accurate cardiac output
      and flow data. Despite recent applications of high-frequency ultrasound Doppler
      to the study of embryonic circulation, current Doppler analysis of volumetric
      flow is relatively crude. To improve Doppler derivation of volumetric flow, we
      sought a preliminary model of the spatial velocity profile in the mouse embryonic
      dorsal aorta using ultrasound biomicroscopy (UBM)-Doppler data. Embryonic
      hematocrit is 0.05-0.10 so rheologic properties must be insignificant. Low
      Reynolds numbers (<500) and Womersley parameters (<0.76) suggest laminar flow.
      UBM demonstrated a circular dorsal aortic cross section with no significant
      tapering. Low Dean numbers (<100) suggest the presence of minimal skewing of the
      spatial velocity profile. The inlet length allows for fully developed flow. There
      is no apparent aortic wall pulsatility. Extrapolation of prior studies to these
      vessel diameters (300-350 microm) and flow velocities (~50-200 mm/s) suggests
      parabolic spatial velocity profiles. Therefore, mouse embryonic dorsal aortic
      blood flow may correspond to Poiseuille flow in a straight rigid tube with
      parabolic spatial velocity profiles. As a first approximation, these results are
      an important step toward precise in utero ultrasound characterization of blood
      flow within the developing mammalian circulation.

PMID- 12181119
TI  - Hypoxia and acidosis impair cGMP synthesis in microvascular coronary endothelial
      cells.
AB  - To characterize the effects of ischemia on cGMP synthesis in microvascular
      endothelium, cultured endothelial cells from adult rat hearts were exposed to
      hypoxia or normoxia at pH 6.4 or 7.4. Cellular cGMP and soluble (sGC) and
      membrane guanylyl cyclase (mGC) activities were measured after stimulation of sGC
      (S-nitroso-N-acetyl-penicillamine) or mGC (urodilatin) or after no stimulation.
      Cell death (lactate dehydrogenase release) was negligible in all experiments.
      Hypoxia at pH 6.4 induced a rapid approximately 90% decrease in cellular cGMP
      after sGC and mGC stimulation. This effect was reproduced by acidosis. Hypoxia at
      pH 7.4 elicited a less pronounced (approximately 50%) and slower reduction in
      cGMP synthesis. Reoxygenation after 2 h of hypoxia at either pH 6.4 or 7.4
      normalized the response to mGC stimulation but further deteriorated the sGC
      response; normalization of pH rapidly reversed the effects of acidosis. At pH
      7.4, the response to GC stimulation correlated well with cellular ATP. We
      conclude that simulated ischemia severely depresses cGMP synthesis in
      microvascular coronary endothelial cells through ATP depletion and acidosis
      without intrinsic protein alteration.

PMID- 12181120
TI  - Dynamics of microvascular oxygen pressure during rest-contraction transition in
      skeletal muscle of diabetic rats.
AB  - Type I diabetes reduces dramatically the capacity of skeletal muscle to receive
      oxygen (QO(2)). In control (C; n = 6) and streptozotocin-induced diabetic (D: n =
      6, plasma glucose = 25.3 +/- 3.9 mmol/l and C: 8.3 +/- 0.5 mmol/l) rats,
      phosphorescence quenching was used to test the hypothesis that, in D rats, the
      decline in microvascular PO(2) [Pm(O(2)), which reflects the dynamic balance
      between O(2) utilization (VO(2)) and QO(2)] of the spinotrapezius muscle after
      the onset of electrical stimulation (1 Hz) would be faster compared with that of
      C rats. Pm(O(2)) data were fit with a one or two exponential process (contingent
      on the presence of an undershoot) with independent time delays using least
      squares regression analysis. In D rats, Pm(O(2)) at rest was lower (C: 31.2 +/-
      3.2 mmHg; D: 24.3 +/- 1.3 mmHg, P < 0.05) and at the onset of contractions
      decreased after a shorter delay (C: 13.5 +/- 1.8 s; D: 7.6 +/- 2.1 s, P < 0.05)
      and with a reduced mean response time (C: 31.4 +/- 3.3 s; D: 23.9 +/- 3.1 s, P <
      0.05). Pm(O(2)) exhibited a marked undershoot of the end-stimulation response in
      D muscles (D: 3.3 +/- 1.1 mmHg, P < 0.05), which was absent in C muscles. These
      results indicate an altered VO(2)-to-QO(2) matching across the rest-exercise
      transition in muscles of D rats.

PMID- 12181121
TI  - The neurotensin fragment AcNT(8-13) inhibits lowering of interstitial fluid
      pressure in rat trachea.
AB  - Injury to soft tissue results in the lowering of interstitial fluid pressure
      (P(if)), plasma protein extravasation, and increased total tissue volume. In this
      study, the effects of N-acetyl neurotensin(8-13) [AcNT(8-13)] on P(if) in rat
      trachea were examined after electrical stimulation (ES) of the vagus nerve. P(if)
      was measured with glass capillaries connected to a servocontrolled
      counterpressure system. In pentobarbital-anesthetized female Wistar rats, the
      P(if) after intravenous saline was -1.8 +/- 0.3 mmHg (means +/- SD) and decreased
      to -5.0 +/- 0.6 mmHg (P < 0.01, n = 9) after ES. AcNT(8-13) (10 microg/kg)
      blocked the fall in P(if) after ES (-2.5 +/- 2.3 mmHg, P < 0.01, n = 8). In
      tracheal tissue from animals pretreated with AcNT(8-13) at the same dose and
      immersed in phosphate-buffered saline (0.15 M, pH 7.4), the rate of fluid
      accumulation in excised tissues was significantly reduced after 2 h. The ability
      of AcNT(8-13) to modulate the fluid mechanics of tracheal interstitium after
      inflammation suggests that it may be a useful tool for studying cell adhesion and
      related factors that maintain structural integrity of connective tissue after
      injury.

PMID- 12181122
TI  - Thrombin stimulates dissociation and induction of HSP27 via p38 MAPK in vascular
      smooth muscle cells.
AB  - We investigated the effects of thrombin on the induction of heat shock proteins
      (HSP) 70 and 27, and the mechanism behind the induction in aortic smooth muscle
      A10 cells. Thrombin increased the level of HSP27 but had little effect on the
      level of HSP70. Thrombin stimulated the accumulation of HSP27 dose dependently
      between 0.01 and 1 U/ml and cycloheximide reduced the accumulation. Thrombin
      stimulated an increase in the level of HSP27 mRNA and actinomycin D suppressed
      the thrombin-increased mRNA level. Thrombin induced the phosphorylation of p38
      mitogen-activated protein kinase (MAPK). The HSP27 accumulation by thrombin was
      reduced by SB-203580 and PD-169316 but not by SB-202474. SB-203580 and PD-169316
      suppressed the thrombin-induced phosphorylation of p38 MAPK. SB-203580 reduced
      the thrombin-increased level of HSP27 mRNA. Dissociation of the aggregated HSP27
      to the dissociated HSP27 was induced by thrombin. Dissociation was inhibited by
      SB-203580. Thrombin induced the phosphorylation of HSP27 and the phosphorylation
      was suppressed by SB-203580. These results indicate that thrombin stimulates not
      only the dissociation of HSP27 but also the induction of HSP27 via p38 MAPK
      activation in aortic smooth muscle cells.

PMID- 12181123
TI  - Cardiac function and metabolism in Type 2 diabetic mice after treatment with BM
      17.0744, a novel PPAR-alpha activator.
AB  - Hearts from diabetic db/db mice, a model of Type 2 diabetes, exhibit left
      ventricular failure and altered metabolism of exogenous substrates. Peroxisome
      proliferator-activated receptor-alpha (PPAR-alpha) ligands reduce plasma lipid
      and glucose concentrations and improve insulin sensitivity in db/db mice.
      Consequently, the effect of 4- to 5-wk treatment of db/db mice with a novel PPAR
      alpha ligand (BM 17.0744; 25-38 mg x kg(-1) x day(-1)), commencing at 8 wk of
      age, on ex vivo cardiac function and metabolism was determined. Elevated plasma
      concentrations of glucose, fatty acids, and triacylglycerol (34.0 +/- 3.6, 2.0 +/
      0.4, and 0.9 +/- 0.1 mM, respectively) were reduced to normal after treatment
      with BM 17.0744 (10.8 +/- 0.6, 1.1 +/- 0.1, and 0.6 +/- 0.1 mM). Plasma insulin
      was also reduced significantly in treated compared with untreated db/db mice.
      Chronic treatment of db/db mice with the PPAR-alpha agonist resulted in a 50%
      reduction in rates of fatty acid oxidation, with a concomitant increase in
      glycolysis (1.7-fold) and glucose oxidation (2.3- fold). Correction of the
      diabetes-induced abnormalities in systemic and cardiac metabolism after BM
      17.0744 treatment did not, however, improve left ventricular contractile
      function.

PMID- 12181124
TI  - Altered dose response to beta-agonists in SERCA1a-expressing hearts ex vivo and
      in vivo.
AB  - In this study we evaluated the contractile characteristics of sarco(endo)plasmic
      reticulum Ca(2+)-ATPase (SERCA)1a-expressing hearts ex vivo and in vivo and in
      particular their response to beta-adrenergic stimulation. Analysis of isolated,
      work-performing hearts revealed that transgenic (TG) hearts develop much higher
      maximal rates of contraction and relaxation than wild-type (WT) hearts. Addition
      of isoproterenol only moderately increased the maximal rate of relaxation (+20%)
      but did not increase contractility or decrease relaxation time in TG hearts.
      Perfusion with varied buffer Ca(2+) concentrations indicated an altered dose
      response to Ca(2+). In vivo TG hearts displayed fairly higher maximal rates of
      contraction (+ 25%) but unchanged relaxation parameters and a blunted but
      significant response to dobutamine. Our study also shows that the phospholamban
      (PLB) level was decreased (-40%) and its phosphorylation status modified in TG
      hearts. This study clearly demonstrates that increases in SERCA protein level
      alter the beta-adrenergic response and affect the phosphorylation of PLB.
      Interestingly, the overall cardiac function in the live animal is only slightly
      enhanced, suggesting that (neuro)hormonal regulations may play an important role
      in controlling in vivo heart function.

PMID- 12181125
TI  - Enhancement of closed-state inactivation in long QT syndrome sodium channel
      mutation DeltaKPQ.
AB  - DeltaKPQ, a three amino acid [lysine (K), proline (P), glutamine (Q)] deletion
      mutation of the human cardiac Na channel (hH1), which is one cause of long QT
      syndrome (LQT3), has impaired inactivation resulting in a late sodium current. To
      better understand inactivation in DeltaKPQ, we applied a site-3 toxin
      anthopleurin A, which has been shown to inhibit inactivation from the open state
      with little or no effect on inactivation from the closed state(s) in wild-type
      hH1. In contrast to the effect of site-3 toxins on wild-type hH1, inactivation
      from closed state(s) in toxin-modified DeltaKPQ demonstrated a large negative
      shift in the Na channel availability curve of nearly -14 mV. Recovery from
      inactivation showed that toxin-modified DeltaKPQ channels recovered slightly
      faster than those in control, whereas development of inactivation at potentials
      negative to -80 mV showed that inactivation developed much more rapidly in toxin
      modified DeltaKPQ channels compared with control. An explanation for our results
      is that closed-state inactivation in toxin-modified DeltaKPQ is enhanced by the
      mutated inactivation lid being positioned "closer" to its receptor resulting in
      an increased rate of association between the inactivation lid and its receptor.

PMID- 12181126
TI  - Echocardiographic assessment of cardiac function in diabetic db/db and transgenic
      db/db-hGLUT4 mice.
AB  - Control db/+ and diabetic db/db mice at 6 and 12 wk of age were subjected to
      echocardiography to determine whether contractile function was reduced in vivo
      and restored in transgenic db/db-human glucose transporter 4 (hGLUT4) mice (12 wk
      old) in which cardiac metabolism has been normalized. Systolic function was
      unchanged in 6-wk-old db/db mice, but fractional shortening and velocity of
      circumferential fiber shortening were reduced in 12-wk-old db/db mice (43.8 +/-
      2.1% and 8.3 +/- 0.5 circs/s, respectively) relative to db/+ control mice (59.5
      +/- 2.3% and 11.8 +/- 0.4 circs/s, respectively). Doppler flow measurements were
      unchanged in 6-wk-old db/db mice. The ratio of E and A transmitral flows was
      reduced from 3.56 +/- 0.29 in db/+ mice to 2.40 +/- 0.20 in 12-wk-old db/db mice,
      indicating diastolic dysfunction. Thus a diabetic cardiomyopathy with systolic
      and diastolic dysfunction was evident in 12-wk-old diabetic db/db mice. Cardiac
      function was normalized in transgenic db/db-hGLUT4 mice, indicating that altered
      cardiac metabolism can produce contractile dysfunction in diabetic db/db hearts.

PMID- 12181127
TI  - Mechanism of RhoA/Rho kinase activation in endothelin-1- induced contraction in
      rabbit basilar artery.
AB  - This study was undertaken to demonstrate the role of the RhoA/Rho kinase pathway
      in endothelin-1 (ET-1)-induced contraction of the rabbit basilar artery.
      Isometric tension and Western blot were used to examine ET-1-induced contraction
      and RhoA activation. The upstream effect on ET-1-induced RhoA activity was
      determined by using ET(A) and ET(B) receptor antagonists, protein kinase C (PKC),
      tyrosine kinase, and phosphatidylinositol-3 kinase inhibitors. The downstream
      effect of ET-1-induced contraction and RhoA activity was studied in the presence
      of the Rho kinase inhibitor Y-27632. The effect of Rho kinase inhibitor on ET-1
      induced myosin light chain (MLC) phosphorylation was investigated by using urea
      glycerol-PAGE immunoblotting. We found 1) ET-1 increased RhoA activity (membrane
      binding RhoA) in a concentration-dependent manner; 2) ET(A), but not ET(B),
      receptor antagonist abolished the effect of ET-1 on RhoA activation; 3)
      phosphodylinositol-3 kinase inhibitor, but not PKC and tyrosine kinase
      inhibitors, reduced ET-1-induced RhoA activation; 4) Rho kinase inhibitor Y-27632
      (10 microM) inhibited ET-1-induced contraction; and 5) ET-1 increased the level
      of MLC phosphorylation. Rho kinase inhibitor Y-27632 reduced the effect of ET-1
      on MLC phosphorylation. This study demonstrated that RhoA/Rho kinase activation
      is involved in ET-1-induced contraction in the rabbit basilar artery.
      Phosphodylinositol-3 kinase and MLC might be the upstream and downstream factors
      of RhoA activation.

PMID- 12181128
TI  - Hypoxia-induced cleavage of caspase-3 and DFF45/ICAD in human failed
      cardiomyocytes.
AB  - It has been proposed that the hemodynamic deterioration associated with heart
      failure (HF) may be due in part to ongoing loss of viable cardiac myocytes
      through apoptosis. Hypoxia has been shown to promote apoptosis in normal
      cardiomyocytes. Adaptation and maladaptations inherent to heart failure can
      modify the susceptibility of cells to different stress factors. We hypothesized
      that HF modifies the threshold of cardiomyocytes to hypoxia-induced apoptosis.
      Cardiomyocytes were isolated from 18 human hearts explanted at the time of
      cardiac transplantation due to either ischemic cardiomyopathy (ICM) (n = 9) or
      idiopathic dilated cardiomyopathy (IDC) (n = 9). Tissue from five normal donor
      hearts (NL) for whom no suitable recipient was available was used as control.
      Cardiomyocytes were incubated for 3 h under normoxic (95% air-5% CO(2)) or
      hypoxic (95% N(2)-5% CO(2)) conditions. Expression of caspase-3 and DNA
      fragmentation factor-45 (DFF45)/inhibitor of caspase-3-activated DNase (ICAD) was
      detected by Western blot analysis. Three hours of hypoxia did not affect the
      expression of these proteins in NL cardiomyocytes. In contrast, hypoxia led to
      cleavage of caspase-3 and DFF45/ICAD both in ICM and IDC. In conclusion, failing
      cardiomyocytes exhibit increased susceptibility to hypoxia-induced apoptosis.

PMID- 12181129
TI  - EDHF, but not NO or prostaglandins, is critical to evoke a conducted dilation
      upon ACh in hamster arterioles.
AB  - Vasomotor reactions upon focal stimulation of arterioles have been shown to be
      conducted along the vascular wall. Such a conduction, which is assumed to reflect
      the spread of electrical signals, may contribute to coordination of responses
      within a vascular segment. We aimed to identify which endothelial autacoid(s) act
      as mediators of the local and conducted dilator responses, respectively. To this
      end, arterioles in the hamster cremaster microcirculation were locally stimulated
      with endothelium-dependent [acetylcholine (ACh)] or endothelium-independent
      dilators [sodium nitroprusside (SNP)], and the resulting changes in diameter were
      measured using a videomicroscopy technique at the site of application and up to
      1.4 mm upstream at distant sites. Experiments were also performed after blockade
      of nitric oxide (NO) synthase, cyclooxygenase, P-450 monooxygenase, or K(+)
      channels. Dilations upon ACh (71 +/- 3%) were conducted rapidly (<1 s) to
      upstream sites (at 1.4 mm: 37 +/- 5%). Although the NO donor SNP induced a
      similar local dilation (71 +/- 7%), this response was not conducted. Maximal
      amplitudes of ACh-induced dilations were not attenuated after inhibition of NO
      synthase and cyclooxygenase at the local and remote sites. However, additional
      treatment with a P-450 monooxygenase blocker (sulfaphenazole) strongly attenuated
      the local response (from 62 +/- 9 to 17 +/- 5%) and abrogated dilations at
      distant sites (at 0.67 mm: from 23 +/- 4% to 4 +/- 3%). Likewise, 17-octadecynoic
      acid strongly attenuated local and remote responses. Blockers of Ca(2+)-dependent
      K(+) channels (charybdotoxin or iberiotoxin) attenuated dilations at the local
      and remote sites after focal application at the ACh stimulation site. In marked
      contrast, treatment of the upstream site with these blockers was without any
      effect. We conclude that upon local stimulation with ACh, a cytochrome P-450
      monooxygenase product is generated that induces local dilation via the activation
      of Ca(2+)-dependent K(+) channels and initiates conduction of the dilation. In
      contrast to the local site, neither activation of these K(+) channels nor the
      synthesis of NO or prostaglandins is necessary to dilate the arterioles at
      remote, distant sites. This suggests that endothelium-derived hyperpolarizing
      factor serves as an important mediator to initiate conducted dilations and, by
      doing so, may act as a key player in the coordination of arteriolar behavior in
      the microcirculatory network.

PMID- 12181130
TI  - MitoK(ATP) opener, diazoxide, reduces neuronal damage after middle cerebral
      artery occlusion in the rat.
AB  - We investigated effects of diazoxide, a selective opener of mitochondrial ATP
      sensitive K(+) (mitoK(ATP)) channels, against brain damage after middle cerebral
      artery occlusion (MCAO) in male Wistar rats. Diazoxide (0.4 or 2 mM in 30 microl
      saline) or saline (sham) was infused into the right lateral ventricle 15 min
      before MCAO. Neurological score was improved 24 h later in the animals treated
      with 2 mM diazoxide (13.8 +/- 0.7, n = 13) compared with sham treatment (9.5 +/-
      0.2, n = 6, P < 0.01). The total percent infarct volume (MCAO vs. contralateral
      side) of sham treatment animals was 43.6 +/- 3.6% (n = 12). Treatment with 2 mM
      diazoxide reduced the infarct volume to 20.9 +/- 4.8% (n = 13, P < 0.05). Effects
      of diazoxide were prominent in the cerebral cortex. The protective effect of
      diazoxide was completely prevented by the pretreatment with 5-hydroxydecanoate
      (100 mM in 10 microl saline), a selective blocker of mitoK(ATP) channels (n = 6).
      These results indicate that selective opening of the mitoK(ATP) channel has
      neuroprotective effects against ischemia-reperfusion injury in the rat brain.

PMID- 12181131
TI  - Role of NO in modulating neuronal activity in superficial dorsal horn of spinal
      cord during exercise pressor reflex.
AB  - Static contraction of hindlimb skeletal muscle in cats induces a reflex pressor
      response. The superficial dorsal horn of the spinal cord is the major site of the
      first synapse of this reflex. In this study, static contraction of the triceps
      surae muscle was evoked by electrical stimulation of the tibial nerve for 2 min
      in anesthetized cats (stimulus parameters: two times motor threshold at 30 Hz,
      0.025-ms duration). Ten stimulations were performed and 1-min rest was allowed
      between stimulations. Muscle contraction caused a maximal increase of 32 +/- 5
      mmHg in mean arterial pressure (MAP), which was obtained from the first three
      contractions. Activated neurons in the superficial dorsal horn were identified by
      c-Fos protein. Distinct c-Fos expression was present in the L6-S1 level of the
      superficial dorsal horn ipsilateral to the contracting leg (88 +/- 14 labeled
      cells per section at L7), whereas only scattered c-Fos expression was observed in
      the contralateral superficial dorsal horn (9 +/- 2 labeled cells per section, P <
      0.05 compared with ipsilateral section). A few c-Fos-labeled cells were found in
      control animals (12 +/- 5 labeled cells per section, P < 0.05 compared with
      stimulated cats). Furthermore, double-labeling methods demonstrated that c-Fos
      protein coexisted with nitric oxide (NO) synthase (NOS) positive staining in the
      superficial dorsal horn. Finally, an intrathecal injection of an inhibitor of
      NOS, N-nitro-L-arginine methyl ester (5 mM), resulted in fewer c-Fos-labeled
      cells (58 +/- 12 labeled cells per section) and a reduced maximal MAP response
      (20 +/- 3 mmHg, P < 0.05). These results suggest that the exercise pressor reflex
      induced by static contraction is mediated by activation of neurons in the
      superficial dorsal horn and that formation of NO in this region is involved in
      modulating the activated neurons and the pressor response to contraction.

PMID- 12181132
TI  - Preconditioning with ethanol prevents postischemic leukocyte-endothelial cell
      adhesive interactions.
AB  - Long-term ethanol consumption at low to moderate levels exerts cardioprotective
      effects in the setting of ischemia and reperfusion (I/R). The aims of this study
      were to determine whether 1) a single orally administered dose of ethanol
      [ethanol preconditioning (EtOH-PC)] would induce a biphasic temporal pattern of
      protection (early and late phases) against the inflammatory responses to I/R and
      2) adenosine and nitric oxide (NO) act as initiators of the late phase of
      protection. Ethanol was administered as a bolus to C57BL/6 mice at a dose that
      achieved a peak plasma concentration of ~45 mg/dl 30 min after gavage and
      returned to control levels within 60 min of alcohol ingestion. The superior
      mesenteric artery was occluded for 45 min followed by 60 min of reperfusion
      beginning 10 min or 1, 2, 3, 4, or 24 h after ethanol ingestion, and the numbers
      of fluorescently labeled rolling and firmly adherent (stationary) leukocytes in
      single postcapillary venules of the small intestine were quantified using
      intravital microscopic approaches. I/R induced marked increases in leukocyte
      rolling and adhesion, effects that were attenuated by EtOH-PC 2-3 h before I/R
      (early phase), absent when assessed after 10 min, 1 h, and 4 h of ethanol
      ingestion, with an even more powerful late phase of protection reemerging when
      I/R was induced 24 h later. The anti-inflammatory effects of late EtOH-PC were
      abolished by treatment with adenosine deaminase, an adenosine A(2) (but not A(1))
      receptor antagonist, or a NO synthase (NOS) inhibitor during the period of EtOH
      PC. Preconditioning with an adenosine A(2) (but not an A(1)) receptor agonist in
      lieu of ethanol 24 h before I/R mimicked the protective actions of late phase
      EtOH-PC. Like EtOH-PC, the effect of preconditioning with an adenosine A(2)
      receptor agonist was abrogated by coincident NOS inhibition. These findings
      suggest that EtOH-PC induces a biphasic temporal pattern of protection against
      the proinflammatory effects of I/R. In addition, our observations are consistent
      with the hypothesis that the late phase of EtOH-PC is triggered by NO formed
      secondary to adenosine A(2) receptor-dependent activation of NOS during the
      period of ethanol exposure.

PMID- 12181133
TI  - Transmural action potential and ionic current remodeling in ventricles of failing
      canine hearts.
AB  - Heart failure (HF) produces important alterations in currents underlying cardiac
      repolarization, but the transmural distribution of such changes is unknown. We
      therefore recorded action potentials and ionic currents in cells isolated from
      the endocardium, midmyocardium, and epicardium of the left ventricle from dogs
      with and without tachypacing-induced HF. HF greatly increased action potential
      duration (APD) but attenuated APD heterogeneity in the three regions. Early
      afterdepolarizations (EADs) were observed in all cell types of failing hearts but
      not in controls. Inward rectifier K(+) current (I(K1)) was homogeneously reduced
      by approximately 41% (at -60 mV) in the three cell types. Transient outward K(+)
      current (I(to1)) was decreased by 43-45% at +30 mV, and the slow component of the
      delayed rectifier K(+) current (I(Ks)) was significantly downregulated by 57%,
      49%, and 58%, respectively, in epicardial, midmyocardial, and endocardial cells,
      whereas the rapid component of the delayed rectifier K(+) current was not
      altered. The results indicate that HF remodels electrophysiology in all layers of
      the left ventricle, and the downregulation of I(K1), I(to1), and I(Ks) increases
      APD and favors occurrence of EADs.

PMID- 12181134
TI  - Oxygen transport across vasa recta in the renal medulla.
AB  - In this model of oxygen transport in the renal medullary microcirculation, we
      predicted that the net amount of oxygen reabsorbed from vasa recta into the
      interstitium is on the order of 10(-6) mmol/s, i.e., significantly lower than
      estimated medullary oxygen requirements based on active sodium reabsorption. Our
      simulations confirmed a number of experimental findings. Low medullary PO(2)
      results from the countercurrent arrangement of vessels and an elevated vasa recta
      permeability to oxygen, as well as high metabolic needs. Diffusional shunting of
      oxygen between descending vasa recta (DVR) and ascending vasa recta also explains
      why a 20-mmHg decrease in initial PO(2) at the corticomedullary junction only
      leads to a small drop in papillary tip PO(2) (<2 mmHg with baseline parameter
      values). Conversely, small changes in the consumption rate of DVR-supplied
      oxygen, in blood flow rate, in hematocrit, or in capillary permeability to
      oxygen, beyond certain values sharply reduce interstitial PO(2). Without
      erythrocytes, papillary tip PO(2) cannot be maintained above 10 mmHg, even when
      oxygen consumption is zero.

PMID- 12181136
TI  - Analysis of right ventricular function in healthy mice and a murine model of
      heart failure by in vivo MRI.
AB  - Because of its complex geometry, assessment of right ventricular (RV) function is
      more difficult than it is for the left ventricle (LV). Because gene-targeted
      mouse models of cardiomyopathy may involve remodeling of the right heart, the
      purpose of this study was to develop high-resolution functional magnetic
      resonance imaging (MRI) for in vivo quantification of RV volumes and global
      function in mice. Thirty-three mice of various age were studied under isoflurane
      anesthesia by electrocardiogram-triggered cine-MRI at 7 T. MRI revealed close
      correlations between RV and LV stroke volume and cardiac output (r = 0.97, P <
      0.0001 each). Consistent with human physiology, murine RV end-diastolic and end
      systolic volumes were significantly higher compared with LV volumes (P < 0.05
      each). MRI in mice with LV heart failure due to myocardial infarction revealed
      significant structural and functional changes of the RV, indicating RV
      dysfunction. Hence, MRI allows for the quantification of RV volumes and global
      systolic function with high accuracy and bears the potential to evaluate
      mechanisms of RV remodeling in mouse models of heart failure.

PMID- 12181135
TI  - Phosphorylation of cardiac protein kinase B is regulated by palmitate.
AB  - In this study isolated perfused working rat hearts were used to investigate the
      role of palmitate-regulated protein kinase B (PKB) phosphorylation on glucose
      metabolism. Rat hearts were perfused aerobically in working mode with 11 mM
      glucose and either 100 microU/ml insulin or 100 microU/ml insulin and 1.2 mM
      palmitate. PKB activity and phosphorylation state were reduced in the presence of
      1.2 mM palmitate, which correlates with a decrease in glycolysis (47%), glucose
      oxidation (84%), and glucose uptake (43%). In contrast to skeletal muscle,
      neither p38 nor ERK underwent changes in their phosphorylation states in response
      to insulin or insulin and palmitate. Moreover, pharmacological restoration of
      glucose oxidation rates in hearts perfused with 1.2 mM palmitate demonstrated no
      increase in PKB phosphorylation state. In cultured mouse cardiac muscle HL-1
      cells, insulin markedly increased PKB phosphorylation, which was blunted by pre-
      and cotreatment with 1.2 mM palmitate. However, neither palmitate nor C(2)
      ceramide treatment of insulin-stimulated cells was able to accelerate PKB
      dephosphorylation beyond that observed following the removal of insulin alone.
      Taken together, these experiments show the control of PKB phosphorylation by
      palmitate is independent of ceramide and suggest that this signaling event may be
      an important regulator of myocardial glucose uptake and oxidation.

PMID- 12181137
TI  - Optimizing ventricular fibers: uniform strain or stress, but not ATP consumption,
      leads to high efficiency.
AB  - The aim of this study was to investigate the influence of fiber orientation in
      the left ventricular (LV) wall on the ejection fraction, efficiency, and
      heterogeneity of the distributions of developed fiber stress, strain and ATP
      consumption. A finite element model of LV mechanics was used with active
      properties of the cardiac muscle described by the Huxley-type cross-bridge model.
      The computed variances of sarcomere length (SL(var)), developed stress (DS(var)),
      and ATP consumption (ATP(var)) have several minima at different transmural
      courses of helix fiber angle. We identified only one region in the used design
      space with high ejection fraction, high efficiency of the LV and relatively small
      SL(var), DS(var), and ATP(var). This region corresponds to the physiological
      distribution of the helix fiber angle in the LV wall. Transmural fiber angle can
      be predicted by minimizing SL(var) and DS(var), but not ATP(var). If ATP(var) was
      minimized, then the transverse fiber angle was considerably underestimated. The
      results suggest that ATP consumption distribution is not regulating the fiber
      orientation in the heart.

PMID- 12181138
TI  - ADP-induced pial arteriolar dilation in ovariectomized rats involves gap
      junctional communication.
AB  - It was previously shown that, despite the loss of nitric oxide (NO) dependence,
      ADP-induced pial arteriolar dilation was not attenuated in estrogen-depleted
      [i.e., ovariectomized (Ovx)] rats. Additional evidence suggested that the NO was
      replaced by an endothelium-dependent hyperpolarizing factor (EDHF)-like
      mechanism. To further characterize the nascent EDHF role in Ovx females, the
      current study was undertaken to test whether, in Ovx rats, ADP-induced pial
      arteriolar dilation retained its endothelial dependence and whether gap junctions
      are involved in that response. A closed cranial window and intravital microscopy
      system was used to monitor pial arteriolar diameter changes in anesthetized rats.
      The endothelial portion of the ADP-induced dilation was evaluated using light dye
      endothelial injury (L/D). The study was organized around three experimental
      approaches. First, the responses of pial arterioles to ADP before and after L/D
      exposure in intact and Ovx female rats were tested. L/D reduced the ADP response
      by 50-70% in both groups, thereby indicating that the endothelium dependence of
      ADP-induced vasodilation is not altered by chronic estrogen depletion. Second,
      the NO synthase inhibitor N(omega)-nitro-L-arginine (L-NNA) and the prostanoid
      synthesis inhibitor indomethacin (Indo) were coapplied. In intact females, L-NNA
      Indo attenuated the response to ADP by 50%, with no further changes upon the
      addition of L/D. On the other hand, L-NNA-Indo did not affect ADP reactivity in
      Ovx rats, but subsequent L/D exposure reduced the ADP response by >50%. The NO
      prostanoid-independent, but endothelium-dependent, nature of the response in Ovx
      females is a hallmark of EDHF participation. Third, gap junctional inhibition
      strategies were applied. A selective inhibitor of gap junctional function, Gap
      27, did not affect ADP reactivity in intact females but reduced the the ADP
      response by 50% in Ovx females. A similar result was obtained following
      application of a connexin43 antisense oligonucleotide. These findings suggest
      that the nascent EDHF dependency of ADP-induced pial arteriolar dilation in Ovx
      females involves connexin43-related gap junctional communication.

PMID- 12181139
TI  - Role of protein phosphatases in hypoxic preconditioning.
AB  - To find a protein kinase C (PKC)-independent preconditioning mechanism, hypoxic
      preconditioning (HP; i.e., 10-min anoxia and 10-min reoxygenation) was applied to
      isolated rat hearts before 60-min global ischemia. HP led to improved recovery of
      developed pressure and reduced end-diastolic pressure in the left ventricle
      during reperfusion. Protection was unaffected by the PKC inhibitor
      bisindolylmaleimide (BIM; 1 micromol/l). It was abolished by the inhibitor of
      protein phosphatases 1 and 2A cantharidin (20 or 5 micromol/l) and partially
      enhanced by the inhibitor of protein phosphatase 2A okadaic acid (5 nmol/l). In
      adult rat cardiomyocytes treated with BIM and exposed to 60-min simulated
      ischemia (anoxia, extracellular pH 6.4), HP led to attenuation of anoxic
      Na(+)/Ca(2+) overload and of hypercontracture, which developed on reoxygenation.
      This protection was prevented by treatment with cantharidin but not with okadaic
      acid. In conclusion, HP exerts PKC-independent protection on ischemic-reperfused
      rat hearts and cardiomyocytes. Protein phosphatase 1 seems a mediator of this
      protective mechanism.

PMID- 12181140
TI  - Microvascular reperfusion injury: rapid expansion of anatomic no reflow during
      reperfusion in the rabbit.
AB  - The aim was to define the degree and time course of reperfusion-related expansion
      of no reflow. In five groups of anesthetized, open-chest rabbits (30-min coronary
      occlusion and different durations of reperfusion), anatomic no reflow was
      determined by injection of thioflavin S at the end of reperfusion and compared
      with regional myocardial blood flow (RMBF; radioactive microspheres) and infarct
      size (triphenyltetrazolium). The area of no reflow progressively increased from
      12.2 +/- 4.2% of the risk area after 2 min of reperfusion to 30.8 +/- 3.1% after
      2 h and 34.9 +/- 3.3% after 8 h and significantly correlated with infarct size
      after 1 h of reperfusion (r = 0.88-0.97). This rapid expansion of no reflow
      predominantly occurred during the first 2 h, finally encompassing approximately
      80% of the infarct size, and was accompanied by a decrease of RMBF within the
      risk area, being hyperemic after 2 min of reperfusion (3.78 +/- 0.75 ml x min(-1)
      x g(-1)) and plateauing at a level of approximately 0.9 ml x min(-1) x g(-1) by 2
      and 8 h of reperfusion (preischemic RMBF: 2.06 +/- 0.01 ml x min(-1) x g(-1)).
      The development of macroscopic hemorrhage lagged behind no reflow, was closely
      correlated with it, and may be the consequence of microvascular damage.

PMID- 12181141
TI  - Enhanced NO and superoxide generation in dysfunctional hearts from endotoxemic
      rats.
AB  - Free radicals have been implicated in the etiology of cardiac dysfunction during
      sepsis, but the actual species responsible remains unclear. We studied the
      alterations in myocardial nitric oxide (NO), superoxide, and peroxynitrite
      generation along with cardiac mechanical function and efficiency in hearts from
      lipopolysaccharide (LPS)-treated rats. Six hours after LPS (4 mg/kg ip) or saline
      (control) treatment, hearts were isolated and perfused for 1 h with recirculating
      Krebs-Henseleit buffer and paced at 300 beats/min. Cardiac work, O(2)
      consumption, and cardiac efficiency were markedly depressed in LPS hearts
      compared with controls. Plasma nitrate/nitrite level was elevated in LPS rats,
      and ventricular NO production was enhanced as measured by electron spin resonance
      spectroscopy, Ca(2+)-independent NO synthase (NOS) activity, and inducible NOS
      immunohistochemistry. Ventricular superoxide production was also enhanced in LPS
      treated hearts as seen by lucigenin chemiluminescence and xanthine oxidase
      activity. Increased nitrotyrosine staining (immunohistochemistry) and higher
      lipid hydroperoxides levels were also detected in LPS-treated hearts, indicating
      oxygen radical-induced stress. Enhanced generation of both NO and superoxide, and
      thus peroxynitrite, occur in dysfunctional hearts from endotoxemic rats.

PMID- 12181142
TI  - Increased vulnerability to inducible atrial fibrillation caused by partial
      cellular uncoupling with heptanol.
AB  - We hypothesized that partial cellular uncoupling produced by low concentrations
      of heptanol increases the vulnerability to inducible atrial fibrillation (AF).
      The epicardial surface of 12 isolated-perfused canine left atria was optically
      mapped before and after 1-50 microM heptanol infusion. At baseline, no sustained
      (>30 s) AF could be induced in any of the 12 tissues. However, after 2 microM
      heptanol infusion, sustained AF was induced in 9 of 12 tissues (P < 0.001).
      Heptanol >5 microM caused loss of 1:1 capture during rapid pacing, causing no AF
      to be induced. AF was initiated by conduction block across the fiber leading to
      reentry, which broke up after one to two rotations into two to four independent
      wavelets that sustained the AF. Heptanol at 2 microM had no effect on the
      cellular action potential duration restitution or on the maximal velocity rate
      over time of the upstroke. The effects of heptanol were reversible. We conclude
      that partial cellular uncoupling by heptanol without changing atrial active
      membrane properties promotes wavebreak, reentry, and AF during rapid pacing.

PMID- 12181143
TI  - Differential distribution of Kir2.1 and Kir2.3 subunits in canine atrium and
      ventricle.
AB  - Ventricular inward rectifier K(+) current (I(K1)) is substantially larger than
      atrial, producing functionally important action potential differences. To
      evaluate possible molecular mechanisms, we recorded I(K1) with patch-clamp
      techniques and studied Kir2.1 and Kir2.3 subunit expression. I(K1) density was
      >10-fold larger in the canine ventricle than atrium. Kir2.1 protein expression
      (Western blot) was 78% greater (P < 0.01) in the ventricle, but Kir2.3 band
      density was 228% greater (P < 0.01) in the atrium. Immunocytochemistry showed
      transverse tubular localization of Kir2.1 in 89% (17 of 19) of ventricular and
      26% (5 of 19, P < 0.0001) of atrial cells. Both exhibited a weakly positive
      Kir2.1 signal at intercalated disks. Kir2.3 was strongly expressed at the
      intercalated disks in all cells and in the transverse tubular regions in 78% (14
      of 18) of atrial and 22% (4 of 18, P < 0.001) of ventricular cells. Tissue
      immunohistochemical results qualitatively resembled isolated cell data. We
      conclude that the expression density and subcellular localization of Kir2.1 and
      Kir2.3 subunits differ in the canine atrium versus ventricle. Overall protein
      density differences are insufficient to explain I(K1) discrepancies, which may be
      related to differences in subcellular distribution.

PMID- 12181144
TI  - Platelets activated by transient coronary occlusion exacerbate ischemia
      reperfusion injury in rat hearts.
AB  - Platelets (Plt) accumulate in reperfused myocardium but their effect on
      myocardial necrosis has not been established. We tested the hypothesis that the
      effect of Plt depends on their activation status. Pig Plt were obtained before 48
      min of coronary occlusion (pre-CO-Plt), 10 min after reperfusion (R-Plt), or
      after a 60-min sham operation (sham-Plt). Plt were infused into isolated rat
      hearts (n = 124) and subsequently submitted to 60 min of ischemia and 60 min of
      reperfusion. P-selectin expression was higher (P = 0.02) in R-Plt than in pre-CO
      Plt or sham-Plt. Lactate dehydrogenase (LDH) release during reperfusion was
      similar in hearts receiving pre-CO-Plt, sham-Plt, or no Plt, but R-Plt increased
      LDH release by 60% (P = 0.004). Activation of pre-CO-Plt with thrombin increased
      P-selectin expression and LDH release (P < 0.001), and these results were
      unaffected by tirofiban. There was a close correlation between P-selectin
      expression and LDH release (r = 0.84; P < 0.001), and myocardial Plt accumulation
      (r = 0.85; P < 0.001). We conclude that the deleterious effect of Plt on
      reperfused myocardium depends on their activation status as represented by P
      selectin expression, which is enhanced by ischemia-reperfusion.

PMID- 12181145
TI  - Scaling vs. nonscaling methods of assessing autonomic tone in streptozotocin
      induced diabetic rats.
AB  - We studied heart rate variability in rats by power scaling spectral analysis
      (PSSA), autoregressive modeling (AR), and detrended fluctuation analysis (DFA),
      assessed stability by coefficient of variation between consecutive 6-h epochs,
      and then compared cross-correlation among techniques. These same parameters were
      checked from baseline conditions through acute and chronic disease states
      (streptozotocin-induced diabetes) followed by therapeutic intervention (insulin).
      Cross-correlation between methods over the entire time period was r = 0.94 (DFA
      and PSSA), r = 0.81 (DFA and AR), and r = 0.77 (AR and PSSA). Under baseline
      conditions the scaling parameter measured by DFA and PSSA and the high-frequency
      (HF) component measured by AR fluctuated around an average value, but these
      fluctuations were different for the three methods. After diabetes induction, a
      strong correlation was found between the HF power and the short-term scaling
      parameter. Despite their differences in methodology, DFA and PSSA assess changes
      in parasympathetic tone as detected by autoregressive modeling.

PMID- 12181146
TI  - Comparison of generalized and gender-specific transfer functions for the
      derivation of aortic waveforms.
AB  - Arterial transfer functions have been promoted for the derivation of central
      aortic waveform characteristics not usually accessible noninvasively, but
      possibly of prognostic significance. The utility of generalized rather than
      gender-specific transfer functions has not been assessed. Invasive central aortic
      and noninvasive radial (Millar Mikro-tip tonometer) blood pressure waveforms were
      recorded simultaneously in 78 subjects (61 male and 17 female). Average transfer
      functions were obtained for the whole group and for each gender by two methods.
      Reverse transformation was performed with the use of each transfer function.
      Measured aortic waveform parameters were compared with those derived using
      average, gender-appropriate, and gender-inappropriate transfer functions.
      Differences in central waveform characteristics were demonstrated between men and
      women. Derived waveform parameters were significantly different from measured
      values [e.g., subendocardial viability index and augmentation index (P < 0.001)].
      A gender-appropriate transfer function significantly improved the derivation of
      some parameters, including systolic pressure and systolic and diastolic pressure
      time integrals (P < 0.05). Generalized arterial transfer functions may not be
      universally applicable across all waveform parameters of potential interest, and
      gender-specific transfer functions may be more appropriate.

PMID- 12181147
TI  - Myocardial infarction in rat eliminates regional heterogeneity of AP profiles,
      I(to) K(+) currents, and [Ca(2+)](i) transients.
AB  - Transient outward K(+) current density (I(to)) has been shown to vary between
      different regions of the normal myocardium and to be reduced in heart disease. In
      this study, we measured regional changes in action potential duration (APD),
      I(to), and intracellular Ca(2+) concentration ([Ca(2+)](i)) transients of
      ventricular myocytes derived from the right ventricular free wall (RVW) and
      interventricular septum (SEP) 8 wk after myocardial infarction (MI). At +40 mV,
      I(to) density in sham-operated hearts was significantly higher (P < 0.01) in the
      RVW (15.0 +/- 0.8 pA/pF, n = 47) compared with the SEP (7.0 +/- 1.1 pA/pF, n =
      18). After MI, I(to) density was not reduced in SEP myocytes but was reduced (P <
      0.01) in RVW myocytes (8.7 +/- 1.0 pA/pF, n = 26) to levels indistinguishable
      from post-MI SEP myocytes. These changes in I(to) density correlated with Kv4.2
      (but not Kv4.3) protein expression. By contrast, Kv1.4 expression was
      significantly higher in the RVW compared with the SEP and increased significantly
      after MI in RVW. APD measured at 50% or 90% repolarization was prolonged, whereas
      peak [Ca(2+)](i) transients amplitude was higher in the SEP compared with the RVW
      in sham myocytes. These regional differences in APD and [Ca(2+)](i) transients
      were eliminated by MI. Our results demonstrate that the significant regional
      differences in I(to) density, APD, and [Ca(2+)](i) between RVW and SEP are linked
      to a variation in Kv4.2 expression, which largely disappears after MI.

PMID- 12181148
TI  - Estrogen increases iNOS expression in the ovine coronary artery.
AB  - Estrogen is believed to protect postmenopausal women from coronary vascular
      disease, in part by increasing production of nitric oxide (NO). In this study, we
      investigated the possibility that transcriptional activation of inducible NO
      synthase (iNOS) is responsible for a component of the estrogen-induced increase
      in coronary blood flow. Twenty-two ewes were instrumented with Doppler flow
      probes on their left circumflex coronary and pulmonary arteries. Nine ewes
      received 17beta-estradiol (1 microg/kg), and the coronary vascular response was
      followed for 16 h. Estradiol significantly increased coronary blood flow by 22 +/
      4% over baseline and the peak response occurred at 2 h (P < 0.01). To examine
      the effect of estrogen on NOS expression in the ovine coronary artery, 17
      noninstrumented animals were killed 2 h after administration of estradiol or
      vehicle. Coronary arteries were analyzed for ovine iNOS and endothelial NOS
      (eNOS) expression by semiquantitative RT-PCR. PCR primers were based on partial
      cDNA clones for ovine eNOS and iNOS isolated as part of this study. The
      expression of iNOS was significantly increased (27-fold) by the administration of
      estradiol, whereas the expression of eNOS was much weaker (2-fold). To confirm
      these effects in vivo, additional instrumented animals received either the
      estrogen receptor (ER) antagonist ICI-182,780 (n = 5), the iNOS antagonist
      dexamethasone (n = 5), or pyrrolidine dithiocarbamic acid, an inhibitor of
      nuclear factor-kappaB (n = 5). All three antagonists inhibited estrogen-induced
      increases in coronary blood flow and increases in cardiac output by over 85%.
      These results strongly support the hypothesis that 17beta-estradiol increases
      coronary blood flow in the unanesthetized nonpregnant ewe via an ER-dependent
      mechanism that results in an increase in both eNOS and iNOS expression.

PMID- 12181149
TI  - A new inbred Wistar-Kyoto rat substrain exhibiting apparent salt sensitivity and
      borderline hypertension.
AB  - The normotensive Wistar-Kyoto (WKY) rat strain is a traditional control for the
      spontaneously hypertensive rat (SHR). We found trait differences between two
      inbred normotensive WKY strains, derived originally from different vendors, and
      compared these two strains from La Jolla-Taconic Farms (WKY/lj-tf) and La Jolla
      Charles River (WKY/lj-cr) with the inbred SHR/lj-cr for cardiovascular, diurnal,
      and activity traits under normal and high (8%) NaCl diets. Marked genetic
      diversity was found between the two vendor-derived WKY. By using an extended
      study design and radiotelemetry, we compared WKY/lj-cr, WKY/lj-tf, and SHR/lj-cr
      with the following results: systolic pressure (120 +/- 1, 133 +/- 1, 168 +/- 3
      mmHg, respectively); diurnal variation in heart rate (DeltaHR: 46 +/- 3, 71 +/-
      4, 57 +/- 2 beats/min, respectively); and salt sensitivity of arterial pressure
      (Deltasystolic: 10 +/- 1, 21 +/- 1, 20 +/- 1 mmHg, respectively). The WKY/lj-tf
      genotype apparently results in compromised control of arterial pressure and heart
      rate, especially during high NaCl intake, and greater susceptibility to high
      pressure (i.e., high NaCl-induced secondary changes). WKY/lj-tf thus constitutes
      a new inbred borderline hypertensive WKY substrain offering unique opportunities
      for genomic studies into the development of genetic hypertension.

PMID- 12181150
TI  - Systemic and microvascular responses to hemorrhagic shock and resuscitation with
      Hb vesicles.
AB  - A phospholipid vesicle encapsulating hemoglobin (Hb vesicle, HbV) has been
      developed to provide O(2)-carrying capacity to plasma expanders. Its ability to
      restore systemic and microcirculatory conditions after hemorrhagic shock was
      evaluated in the dorsal skinfold window preparation of conscious hamsters. The
      HbV was suspended in 8% human serum albumin (HSA) at Hb concentrations of 3.8
      g/dl [HbV(3.8)/HSA] and 7.6 g/dl [HbV(7.6)/HSA]. Shock was induced by 50% blood
      withdrawal, and mean arterial pressure (MAP) at 40 mmHg was maintained for 1 h by
      the additional blood withdrawal. The hamsters receiving either HbV(3.8)/HSA or
      HbV(7.6)/HSA suspensions restored MAP to 93 +/- 14 and 93 +/- 10 mmHg,
      respectively, similar with those receiving the shed blood (98 +/- 13 mmHg), which
      were significantly higher by comparison with resuscitation with HSA alone (62 +/-
      12 mmHg). Only the HSA group tended to maintain hyperventilation and negative
      base excess after the resuscitation. Subcutaneous microvascular blood flow
      reduced to approximately 10-20% of baseline during shock, and reinfusion of shed
      blood restored blood flow to approximately 60-80% of baseline, an effect
      primarily due to the sustained constriction of small arteries A(0) (diameter 143
      +/- 29 microm). The HbV(3.8)/HSA group had significantly better microvascular
      blood flow recovery and nonsignificantly better tissue oxygenation than of the
      HSA group. The recovery of base excess and improved tissue oxygenation appears to
      be primarily due to the increased oxygen-carrying capacity of HbV fluid
      resuscitation.

PMID- 12181151
TI  - Evidence of unbalanced regulatory mechanism of heart rate and systolic pressure
      after acute myocardial infarction.
AB  - The interactions between systolic arterial pressure (SAP) and R-R interval (RR)
      fluctuations after acute myocardial infarction (AMI) were investigated by
      measures of synchronization separating the feedback from the feedforward control
      and capturing both linear and nonlinear contributions. The causal
      synchronization, evaluating the ability of RR to predict SAP (chi(s/t)) or vice
      versa (chi(t/s)), and the global synchronization (chi) were estimated at rest and
      after head-up tilt in 35 post-AMI patients, 20 young and 12 old. Significance and
      nonlinearity of the coupling were assessed by surrogate data analysis. Tilting
      increased the number of young subjects in which RR-SAP link was significant (from
      17 to 19) and linear (from 11 to 18). In AMI, both significance and linearity of
      the coupling were low at rest (26 significant and 24 nonlinear) and further
      reduced after tilt (17 significant and 16 nonlinear). Old subjects showed a
      partial recovery of linearity after tilt (rest: 1 linear of 7 significant; tilt:
      5 linear of 8 significant). In young subjects, the causal synchronization indexes
      were balanced and increased from rest (chi(t/s) = 0.072 +/- 0.037 and chi(s/t) =
      0.054 +/- 0.028) to tilt (chi(t/s) = 0.125 +/- 0.071 and chi(s/t) = 0.108 +/-
      0.053). On the contrary, in old subjects and AMI patients, the feedforward was
      prevalent to the feedback coupling at rest (old: chi(t/s) = 0.041 +/- 0.023 and
      chi(s/t) = 0.069 +/- 0.042; AMI: chi(t/s) = 0.050 +/- 0.030 and chi(s/t) = 0.089
      +/- 0.053). Tilting blunted the unbalance in old subjects (chi(t/s) = 0.065 +/-
      0.052 and chi(s/t) = 0.069 +/- 0.044) but not in AMI patients (chi(t/s) = 0.040
      +/- 0.019 and chi(s/t) = 0.060 +/- 0.040). Thus, after AMI, nonlinear mechanisms
      are elicited in RR-SAP interactions. Furthermore, the neural regulation of the
      cardiovascular system resulted in imbalance as a consequence of impaired feedback
      and enhanced feedforward control mechanisms.

PMID- 12181152
TI  - Role of cardiac eNOS expression during pregnancy in the coupling of myocardial
      oxygen consumption to cardiac work.
AB  - We assessed whether pregnancy results in enhanced nitric oxide (NO)-mediated
      control of myocardial oxygen consumption. Rats were studied before (C), at 1 wk
      (1w) or 2 wk (2w) of pregnancy, and at 4 days after giving birth (-4d). Left
      ventricular endothelial NO synthase (eNOS) protein expression was determined by
      immunoblotting. Oxygen consumption of left ventricular tissue samples was
      measured in vitro in response to increasing doses of bradykinin with or without
      addition of the NOS inhibitor N(G)-nitro-L-arginine methyl ester (L-NAME).
      Echocardiography indicated an increased cardiac output during pregnancy.
      Myocardial eNOS protein expression significantly increased by 46 +/- 9 and 39 +/-
      8% at 1w and 2w, respectively, and returned to control levels at -4d. Bradykinin
      (10(-4) M) decreased cardiac oxygen consumption in a NO-dependent manner by 17 +/
      2% at C, by 21 +/- 2% at 1w, by 24 +/- 2% at 2w (P < 0.05 vs. C and -4d), and by
      18 +/- 1% at -4d. Myocardial eNOS protein expression is transiently increased
      during pregnancy in rats, and this increase is associated with enhanced NO
      dependent control of myocardial oxygen consumption at a time when cardiac output
      is increased.

PMID- 12181153
TI  - Troponin I serines 43/45 and regulation of cardiac myofilament function.
AB  - We studied Ca(2+) dependence of tension and actomyosin ATPase rate in detergent
      extracted fiber bundles isolated from transgenic mice (TG), in which cardiac
      troponin I (cTnI) serines 43 and 45 were mutated to alanines (cTnI S43A/S45A).
      Basal phosphorylation levels of cTnI were lower in TG than in wild-type (WT)
      mice, but phosphorylation of cardiac troponin T was increased. Compared with WT,
      TG fiber bundles showed a 13% decrease in maximum tension and a 20% increase in
      maximum MgATPase activity, yielding an increase in tension cost. Protein kinase C
      (PKC) activation with endothelin (ET) or phenylephrine plus propranolol (PP)
      before detergent extraction induced a decrease in maximum tension and MgATPase
      activity in WT fibers, whereas ET or PP increased maximum tension and stiffness
      in TG fibers. TG MgATPase activity was unchanged by ET but increased by PP.
      Measurement of protein phosphorylation revealed differential effects of agonists
      between WT and TG myofilaments and within the TG myofilaments. Our results
      demonstrate the importance of PKC-mediated phosphorylation of cTnI S43/S45 in the
      control of myofilament activation and cross-bridge cycling rate.

PMID- 12181154
TI  - Normal contractions triggered by I(Ca,L) in ventricular myocytes from rats with
      postinfarction CHF.
AB  - Attenuated L-type Ca(2+) current (I(Ca,L)), or current-contraction gain have been
      proposed to explain impaired cardiac contractility in congestive heart failure
      (CHF). Six weeks after coronary artery ligation, which induced CHF, left
      ventricular myocytes from isoflurane-anesthetized rats were current or voltage
      clamped from -70 mV. In both cases, contraction and contractility were attenuated
      in CHF cells compared with cells from sham-operated rats when cells were only
      minimally dialyzed using high-resistance microelectrodes. With patch pipettes,
      cell dialysis caused attenuation of contractions in sham cells, but not CHF
      cells. Stepping from -50 mV, the following variables were not different between
      sham and CHF, respectively: peak I(Ca,L) (4.5 +/- 0.3 vs. 3.8 +/- 0.3 pApF(-1) at
      23 degrees C and 9.4 +/- 0.5 vs. 8.4 +/- 0.5 pApF(-1) at 37 degrees C), the bell
      shaped voltage-contraction relationship in Cs(+) solutions (fractional
      shortening, 15.2 +/- 1.0% vs. 14.3 +/- 0.7%, respectively, at 23 degrees C and
      7.5 +/- 0.4% vs. 6.7 +/- 0.5% at 37 degrees C) and the sigmoidal voltage
      contraction relationship in K(+) solutions. Caffeine-induced Ca(2+) release and
      sarcoplasmic reticulum Ca(2+)-ATPase-to-phospholamban ratio were not different.
      Thus CHF contractions triggered by I(Ca,L) were normal, and the contractile
      deficit was only seen in undialyzed cardiomyocytes stimulated from -70 mV.

PMID- 12181155
TI  - Effects of homocysteine on intracellular nitric oxide and superoxide levels in
      the renal arterial endothelium.
AB  - The present study was designed to test the hypothesis that homocysteine (Hcys)
      reduces intracellular nitric oxide (NO) concentrations ([NO](i)) and stimulates
      superoxide (O.) production in the renal arterial endothelium, thereby resulting
      in endothelial dysfunction. With the use of fluorescence microscopic imaging
      analysis, a calcium ionophore, A-23187 (2 microM), and bradykinin (2 microM) were
      found to increase endothelial [NO](i) in freshly dissected lumen-opened small
      renal arteries loaded with 4,5-diaminofluorescein diacetate (DAF-2DA; 10 microM).
      Preincubation of the arteries with L-Hcys (20-40 microM) significantly attenuated
      the increase in endothelial [NO](i). However, L-Hcys had no effect on NO synthase
      activity in the renal arteries, as measured by the conversion rate of
      [(3)H]arginine to [(3)H]citrulline, but it concentration dependently decreased
      DAF-2DA-sensitive fluorescence induced by PAPA-NONOate in the solution,
      suggesting that L-Hcys reduces endothelial [NO](i) by its scavenging action.
      Because other thiol compounds such as L-cysteine and glutathione were also found
      to reduce [NO](i), it seems that decreased NO is not the only mechanism resulting
      in endothelial dysfunction or arteriosclerosis in hyperhomocysteinemia (hHcys).
      By analysis of intracellular O. levels using dihydroethidium trapping, we found
      that only L-Hcys among the thiol compounds studied markedly increased O. levels
      in the renal endothelium. These results indicate that L-Hcys inhibits the agonist
      induced NO increase but stimulates O. production within endothelial cells. These
      effects of L-Hcys on [NO](i) and [O.] may contribute to endothelial injury
      associated with hHcys.

PMID- 12181156
TI  - Nonreentrant focal activations in pulmonary veins in canine model of sustained
      atrial fibrillation.
AB  - Repetitive rapid activities are present in the pulmonary veins (PVs) in dogs with
      pacing-induced sustained atrial fibrillation (AF). The mechanisms are unclear. We
      induced sustained (>48 h) AF by rapidly pacing the left atrium (LA) in six dogs.
      High-density computerized mapping was done in the PVs and atria. Results show
      repetitive focal activations in all dogs and in 12 of 18 mapped PVs. Activation
      originated from the middle of the PV and then propagated to the LA and distal PV
      with conduction blocks. The right atrium (RA) was usually activated by a single
      large wavefront. Mean AF cycle length in the PVs (left superior, 82 +/- 6 ms;
      left inferior, 83 +/- 6 ms; right inferior, 83 +/- 4 ms) and LA posterior wall
      (87 +/- 5 ms) were significantly (P < 0.05) shorter than those in the LA anterior
      wall (92 +/- 4 ms) and RA (107 +/- 5 ms). PVs in normal dogs did not have focal
      activations during induced AF. No reentrant wavefronts were demonstrated in the
      PVs. We conclude that nonreentrant focal activations are present in the PVs in a
      canine model of pacing-induced sustained AF.

PMID- 12181157
TI  - Alterations of beta-adrenergic signaling and cardiac hypertrophy in transgenic
      mice overexpressing TGF-beta(1).
AB  - Transforming growth factor-beta(1) (TGF-beta(1)) promotes or inhibits cell
      proliferation and induces fibrotic processes and extracellular matrix production
      in numerous cell types. Several cardiac diseases are associated with an increased
      expression of TGF-beta(1) mRNA, particularly during the transition from stable
      cardiac hypertrophy to heart failure. In vitro studies suggest a link between TGF
      beta(1) signaling and the beta-adrenergic system. However, the in vivo effects of
      this growth factor on myocardial tissue have been poorly identified. In
      transgenic mice overexpressing TGF-beta(1) (TGF-beta), we investigated the in
      vivo effects on cardiac morphology, beta-adrenergic signaling, and contractile
      function. When compared with nontransgenic controls (NTG), TGF-beta mice revealed
      significant cardiac hypertrophy (heart weight, 164 +/- 7 vs. 130 +/- 3 mg, P <
      0.01; heart weight-to-body weight ratio, 6.8 +/- 0.3 vs. 5.1 +/- 0.1 mg/g, P <
      0.01), accompanied by interstitial fibrosis. These morphological changes
      correlated with an increased expression of hypertrophy-associated proteins such
      as atrial natriuretic factor (ANF). Furthermore, overexpression of TGF-beta(1)
      led to alterations of beta-adrenergic signaling as myocardial beta-adrenoceptor
      density increased from 7.3 +/- 0.3 to 11.2 +/- 1.1 fmol/mg protein (P < 0.05),
      whereas the expression of beta-adrenoceptor kinase-1 and inhibitory G proteins
      decreased by 56 +/- 9.7% and 58 +/- 7.6%, respectively (P < 0.05). As a
      consequence of altered beta-adrenergic signaling, hearts from TGF-beta showed
      enhanced contractile responsiveness to isoproterenol stimulation. In conclusion,
      we conclude that TGF-beta(1) induces cardiac hypertrophy and enhanced beta
      adrenergic signaling in vivo. The morphological alterations are either induced by
      direct effects of TGF-beta(1) or may at least in part result from increased beta
      adrenergic signaling, which may contribute to excessive catecholamine stimulation
      during the transition from compensated hypertrophy to heart failure.

PMID- 12181158
TI  - Sildenafil (Viagra) induces powerful cardioprotective effect via opening of
      mitochondrial K(ATP) channels in rabbits.
AB  - Sildenafil citrate (Viagra) is the pharmacological agent used to treat erectile
      dysfunction in men. Because this drug has a vasodilatory effect, we hypothesized
      that such an action may induce a preconditioning-like cardioprotective effect via
      opening of mitochondrial ATP-sensitive K (K(ATP)) channels. Rabbits were treated
      with sildenafil citrate (0.7 mg/kg iv) either 30 min (acute phase) or 24 h
      (delayed phase) before 30 min of ischemia and 3 h of reperfusion. Mitochondrial
      K(ATP) channel blocker 5-hydroxydecanoate (5-HD, 5 mg/kg iv) was given 10 min
      before ischemia-reperfusion. Infarct size was measured by tetrazolium staining.
      Sildenafil caused reduction in arterial blood pressure within 2 min of treatment,
      which returned to nearly baseline levels 3 min later. The infarct size (% risk
      area, means +/- SE) reduced from 33.8 +/- 1.7 in control rabbits to 10.8 +/- 0.9
      during the acute phase (68% reduction, P < 0.05) and 19.9 +/- 2.0 during the
      delayed phase (41% reduction, P < 0.05). 5-HD abolished protection with an
      increase in infarct size to 35.6 +/- 0.4% and 36.8 +/- 1.6% during the acute and
      delayed phase, respectively (P < 0.05). Similar acute and delayed
      cardioprotective effects were observed when sildenafil was administered orally.
      Systemic hemodynamics also decreased after oral administration of the drug.
      However, these changes were mild and occurred slowly. For the first time, we
      demonstrate that sildenafil induces acute and delayed protective effects against
      ischemia-reperfusion injury, which are mediated by opening of mitochondrial
      K(ATP) channels.

PMID- 12181159
TI  - Aging and neural control of the GI tract. I. Age-related changes in the enteric
      nervous system.
AB  - As we enter the 21st century, the segment of the population that is the most
      rapidly expanding is that comprised of individuals 85 yr of age and older.
      Dysfunctions of the gastrointestinal (GI) system, including dysphagia,
      constipation, diarrhea, and irritable bowel syndrome are more common complaints
      of the elderly, yet our knowledge of the aging GI tract is incomplete. Compared
      with the rapid advances in the neurobiology of aging in the central nervous
      system, the understanding of age-related changes in the enteric nervous system
      (ENS) is poor. In this brief review, I recap experiments that reveal
      neurodegenerative changes and their functional correlates in the ENS of mice,
      rats, and guinea pigs. Clinical literature seems indicative of similar structural
      and functional age-related changes in the human ENS. Current studies that address
      the mechanisms underlying age-related changes in the ENS are introduced. The
      future directions for this field include physiological and pharmacological
      studies, especially at cellular and molecular levels. Research in the aging ENS
      is poised to make major advances, and this new knowledge will be useful for
      clinicians seeking to better understand and treat GI dysfunction in the elderly.

PMID- 12181160
TI  - The epithelial cell cytoskeleton and intracellular trafficking. III. How is
      villin involved in the actin cytoskeleton dynamics in intestinal cells?
AB  - Villin plays a key role in the maintenance of the brush border organization by
      bundling F-actin into a network of parallel filaments. Our previous in vivo data
      on villin knockout mice showed that, although this protein is not necessary for
      the bundling of F-actin, it is important for the reorganization of the actin
      cytoskeleton elicited by stress conditions. We further investigated villin
      property to initiate actin remodeling in cellular processes such as hepatocyte
      growth factor-induced motility, morphogenesis, and bacterial infection. Our data
      suggest that villin is involved in actin remodeling necessary for many cellular
      processes requiring the actin cytoskeleton plasticity.

PMID- 12181161
TI  - Ca2+- and PKC-dependent stimulation of PGE2 synthesis by deoxycholic acid in
      human colonic fibroblasts.
AB  - We investigated prostanoid biogenesis by human colonic fibroblasts (CCD-18Co
      cells and nine primary fibroblast cultures) exposed to a primary (cholic, CA) or
      a secondary (deoxycholic, DCA) bile acid. Basal PGE2 levels in CCD-18Co cultures
      and fibroblast strains initiated from normal and adenocarcinomatous colon,
      respectively, were 1.7 +/- 0.3, 4.0 +/- 2.0, and 15.0 +/- 4.8 ng/mg protein. Peak
      levels 24 h after exposure to DCA (300 microM) rose, respectively, seven-, six-
      and sevenfold, but CA elicited no such responses. Increases in PGE2 synthesis
      were preceded by sequential increases in PGH synthase-2 mRNA and protein
      expression and were fully prevented by a nonselective (indomethacin) or a
      selective (celecoxib) nonsteroidal anti-inflammatory drug. DCA, but not CA,
      caused abrupt, transient increases in fibroblast intracellular Ca2+ concentration
      ([Ca2+]i) approximately 1 min after exposure. Increased [Ca2+]i was required for
      DCA-mediated induction of PGE2 synthesis, and protein kinase C was a further
      essential component of this signaling pathway. Colonic fibroblasts may be a major
      target for prostanoid biogenesis induced by fecal bile acids and, potentially,
      other noxious actions of these agents.

PMID- 12181163
TI  - Effects of peptides derived from dietary proteins on mucus secretion in rat
      jejunum.
AB  - The hypothesis that dietary proteins or their hydrolysates may regulate
      intestinal mucin discharge was investigated in the isolated vascularly perfused
      rat jejunum using an enzyme-linked immunosorbent assay for rat intestinal mucins.
      On luminal administration, casein hydrolysate [0.05-5% (wt/vol)] stimulated mucin
      secretion in rat jejunum (maximal response at 417% of controls). Lactalbumin
      hydrolysate (5%) also evoked mucin discharge. In contrast, casein, and a mixture
      of amino acids was without effect. Chicken egg albumin and its hydrolysate or
      meat hydrolysate also did not modify mucin release. Interestingly, casein
      hydrolysate-induced mucin secretion was abolished by intra-arterial TTX or
      naloxone (an opioid antagonist). beta-Casomorphin-7, an opioid peptide released
      from beta-casein on milk ingestion, induced a strong mucin secretion (response at
      563% of controls) that was inhibited by naloxone. Intra-arterial beta-casomorphin
      7 also markedly increased mucin secretion (410% of controls). In conclusion, two
      enzymatic milk protein hydrolysates (casein and lactalbumin hydrolysates) and
      beta-casomorphin-7, specifically, induced mucin release in rat jejunum. The
      casein hydrolysate-induced mucin secretion is triggered by a neural pathway and
      mediated by opioid receptor activation.

PMID- 12181162
TI  - NSAIDs counteract H. pylori VacA toxin-induced cell vacuolation in MKN 28 gastric
      mucosal cells.
AB  - The relationship between nonsteroidal anti-inflammatory drugs (NSAIDs) and
      Helicobacter pylori-induced gastric mucosal injury is still under debate. VacA
      toxin is an important H. pylori virulence factor that causes cytoplasmic
      vacuolation in cultured cells. Whether and how NSAIDs affect VacA-induced
      cytotoxicity is unclear. This study was designed to evaluate the effect of NSAIDs
      on H. pylori VacA toxin-induced cell vacuolation in human gastric mucosal cells
      in culture (MKN 28 cell line). Our data show that 1) NSAIDs (indomethacin,
      aspirin, and NS-398) inhibit VacA-induced cell vacuolation independently of
      inhibition of cell proliferation and prostaglandin synthesis; 2) NSAIDs impair
      vacuole development/maintenance without affecting cell binding and
      internalization of VacA; and 3) NSAIDs, as well as the chloride channel blocker 5
      nitro-2-(3-phenylpropylamino) benzoic acid, also inhibit cell vacuolation induced
      by ammonia. We thus hypothesize that NSAIDs might protect MKN 28 cells against
      VacA-induced cytotoxicity by inhibiting VacA channel activity required for
      vacuole genesis.

PMID- 12181164
TI  - Mechanisms of airway protection during retching, vomiting, and swallowing.
AB  - We investigated the mechanisms of airway protection and bolus transport during
      retching and vomiting by recording responses of the pharyngeal, laryngeal, and
      hyoid muscles and comparing them with responses during swallowing and responses
      of the gastrointestinal tract. Five dogs were chronically instrumented with
      electrodes on the striated muscles and strain gauges on smooth muscles. Retching
      and vomiting were stimulated by apomorphine (5-10 ug/kg iv). During retching, the
      hyoid and thyroid descending and laryngeal abductor muscles were activated;
      between retches, the hyoid, thyroid, and pharyngeal elevating, and laryngeal
      adductor muscles were activated. Vomiting always occurred during the ascending
      phase of retching and consisted of three sequential phases of hyoid and
      pharyngeal muscle activation culminating in simultaneous activation of all
      recorded elevating and descending laryngeal, hyoid, and pharyngeal muscles.
      Retrograde activation of esophagus and pharyngeal muscles occurred during the
      later phases, and laryngeal adductor was maximally activated in all phases of the
      vomit. During swallowing, the laryngeal adductor activation was followed
      immediately by brief activation of the laryngeal abductor. We concluded that
      retching functions to mix gastric contents with refluxed intestinal secretions
      and to impart an orad momentum to the bolus before vomiting. During retches, the
      airway is protected by glottal closure, and between retches, it is protected by
      ascent of the larynx and closure of the upper esophageal sphincter. The airway is
      protected by maximum glottal closure during vomiting. During swallowing, the
      airway is protected by laryngeal elevation and glottal closure followed by brief
      opening of the glottis, which may release subglottal pressure expelling material
      from the laryngeal vestibule.

PMID- 12181165
TI  - Role of ICAM-1 in chronic ethanol consumption-enhanced liver injury after gut
      ischemia-reperfusion in rats.
AB  - Intercellular adhesion molecule-1 (ICAM-1) has been implicated in the hepatic
      microvascular dysfunction elicited by gut ischemia-reperfusion (I/R). Although
      the effects of chronic ethanol (EtOH) consumption on the liver are well known, it
      remains unclear whether this condition renders the hepatic microcirculation more
      vulnerable to the deleterious effects of gut and/or hepatic I/R. The objectives
      of this study were to determine whether chronic EtOH consumption alters the
      severity of gut I/R-induced hepatic microvascular dysfunction and hepatocellular
      injury and to determine whether ICAM-1 contributes to this response. Male Wistar
      rats, pair fed for 6 wk a liquid diet containing EtOH or an isocaloric control
      diet, were exposed to gut I/R. Intravital video microscopy was used to monitor
      leukocyte recruitment in the hepatic microcirculation, the number of nonperfused
      sinusoids (NPS), and plasma concentrations of endotoxin and tumor necrosis factor
      alpha. Plasma alanine aminotransferase (ALT) levels were measured 6 h after the
      onset of reperfusion. In control rats, gut I/R elicited increases in the number
      of stationary leukocytes, NPS, and plasma endotoxin, tumor necrosis factor-alpha,
      and ALT. In EtOH-fed rats, the gut I/R-induced increases in NPS and leukostasis
      were blunted in the midzonal region, while exaggerated leukostasis was noted in
      the pericentral region and terminal hepatic venules. Chronic EtOH consumption
      also enhanced the gut I/R-induced increase in plasma endotoxin and ALT. The
      exaggerated responses to gut I/R normally seen in EtOH-fed rats were largely
      prevented by pretreatment with a blocking anti-ICAM-1 monoclonal antibody. In
      conclusion, these results suggest that chronic EtOH consumption enhances gut I/R
      induced hepatic microvascular dysfunction and hepatocellular injury in the
      pericentral region and terminal hepatic venules via an enhanced hepatic
      expression of ICAM-1.

PMID- 12181166
TI  - Cholinergic and nitrergic regulation of in vivo giant migrating contractions in
      rat colon.
AB  - The aim of this study was to characterize in vivo rat colonic motor activity in
      normal and inflamed states and determine its neural regulation. Circular muscle
      contractions were recorded by surgically implanted strain-gauge transducers. The
      rat colon exhibited predominantly giant migrating contractions (GMCs) whose
      frequency decreased distally. Only a small percentage of these GMCs propagated in
      the distal direction; the rest occurred randomly. Phasic contractions were
      present, but their amplitude was very small compared with that of GMCs.
      Inflammation induced by oral administration of dextran sodium sulfate suppressed
      the frequency of GMCs in the proximal and middle but not in the distal colon.
      Frequency of GMCs was suppressed by intraperitoneally administered atropine and 4
      diphenylacetoxy-N-methyl-piperidine methiodide and was enhanced by N(w)-nitro-L
      arginine methyl ester. Serotonin, tachykinin, and calcitonin gene-related peptide
      receptor or receptor subtype antagonists as well as guanethidine and suramin had
      no significant effect on the frequency of GMCs. Verapamil transiently suppressed
      the GMCs. In conclusion, unlike the canine and human colons, the rat colon
      exhibits frequent GMCs and their frequency is suppressed in inflammation. In vivo
      GMCs are stimulated by neural release of acetylcholine that acts on M3 receptors.
      Constitutive release of nitric oxide may partially suppress their frequency.

PMID- 12181167
TI  - Poly(ADP-ribose) polymerase triggers the microvascular mechanisms of hepatic
      ischemia-reperfusion injury.
AB  - Activation of poly(ADP-ribose) polymerase (PARP) mediates oxidative stress
      induced cell injury. We tested the hypothesis that PARP contributes to ischemia
      reperfusion (I/R) damage of the liver by triggering the mechanisms of
      microcirculatory failure. Leukocyte- and platelet-endothelial cell interactions
      as well as sinusoidal perfusion were analyzed by intravital fluorescence
      microscopy after lobar hepatic I/R (90 min/30 min) in C57BL/6 x 129/Sv wild-type
      (PARP+/+) and PARP-deficient (PARP-/-) mice. Hepatic I/R induced
      leukocyte/platelet-endothelial cell interactions and tissue injury in PARP+/+
      mice, as indicated by impaired sinusoidal perfusion and increased alanine
      aminotransferase (ALT)/aspartate aminotransferase (AST) serum activities. In PARP
      /- mice, however, the postischemic increase in the numbers of rolling/adherent
      leukocytes and platelets was significantly lower. In addition, I/R-induced
      translocation of CD62P as well as mRNA expression of CD62E, CD54, and CD106 were
      attenuated. The degree of perfusion failure was reduced and the increase in the
      ALT/AST activities was lower in PARP-/- mice compared with PARP+/+ mice. We
      conclude that PARP contributes to hepatic microvascular injury by triggering the
      expression/translocation of adhesion molecules and modulating leukocyte/platelet
      endothelial cell interactions.

PMID- 12181168
TI  - Hepatic leukocyte recruitment in a model of acute colitis.
AB  - There is a close relationship between inflammatory bowel disease (IBD) and
      various hepatobiliary disorders. The objective of this study was to determine
      whether hepatic leukocyte recruitment occurs in experimental colitis. We used the
      murine model of colitis induced by 2,4-dinitrobenezenesulfonic acid (DNBS). Male
      C57Bl/6 mice received an intrarectal injection of 4 mg DNBS in 100 microl 50%
      ethanol. Controls received 100 microl 50% ethanol. The hepatic microcirculation
      was examined at 3 and 14 days post-DNBS by intravital video microscopy. Three
      days post-DNBS, when mice had developed acute colitis, there was associated
      hepatic leukocyte recruitment. Within the postsinusoidal venules there was a
      fourfold increase in the flux of rolling leukocytes that was P-selectin dependent
      but not alpha(4)-integrin dependent. There was also an increase in stationary
      leukocytes within the sinusoids, although this was not associated with an
      increase in serum alanine transaminase. By 14 days post-DNBS when macroscopic
      evidence of colonic inflammation was resolved, rolling within the postsinusoidal
      venules had returned to control levels. In this murine model of colitis, we
      describe a link between acute colonic inflammation and remote hepatic leukocyte
      recruitment that is P-selectin dependent. Active IBD may lead to remote hepatic
      inflammation.

PMID- 12181169
TI  - Upregulation of CFTR expression but not SLC26A3 and SLC9A3 in ulcerative colitis.
AB  - In inflamed colonic mucosa, the equilibrium between absorptive and secretory
      functions for electrolyte and salt transport is disturbed. We compared the
      expression of three major mediators of the intestinal salt transport between
      healthy and inflamed colonic mucosa to understand the pathophysiology of diarrhea
      in inflammatory bowel disease. Expression levels of the cystic fibrosis
      transmembrane regulator (CFTR) (Cl- channel), SLC26A3 (Cl-/HCO exchanger) and
      SLC9A3 (Na+/H+ exchanger) mRNAs were measured by real-time quantitative RT-PCR in
      peroperative colonic samples from controls (n = 4) and patients with ulcerative
      colitis (n = 10). Several samples were obtained from each individual. Tissue
      samples were divided into three subgroups according to their histological degree
      of inflammation. Expression of CFTR and SLC26A3 proteins were determined by
      immunohistochemistry and Western blotting from the same samples, respectively.
      Increased expression of CFTR mRNA was observed in all three groups of affected
      tissue samples, most pronounced in mildly inflamed colonic mucosa (5-fold
      increase in expression; P < 0.001). The expression of the CFTR protein was
      detected from health and inflamed colon tissue. Although the expression of the
      SLC26A3 mRNA was significantly decreased in severe ulcerative colitis (P < 0.05),
      the SLC26A3 protein levels remained unchanged in all groups. The expression of
      SLC9A3 mRNA was significantly changed between the mild and severe groups.
      Intestinal inflammation modulates the expression of three major mediators of
      intestinal salt transport and may contribute to diarrhea in ulcerative colitis
      both by increasing transepithelial Cl- secretion and by inhibiting the epithelial
      NaCl absorption.

PMID- 12181170
TI  - Physiological and morphological effects of alendronate on rabbit esophageal
      epithelium.
AB  - Alendronate, an aminobisphosphonate, produces as a side effect a topical (pill
      induced) esophagitis. To gain insight into this phenomenon, we assessed the
      effects of luminal alendronate on both esophageal epithelial structure and
      function. Sections of rabbit esophageal epithelium were exposed to luminal
      alendronate at neutral or acidic pH while mounted in Ussing chambers to monitor
      transmural electrical potential difference (PD), short-circuit current (I(sc)),
      and resistance (R). Morphological changes were sought by light microscopy in
      hematoxylin and eosin-stained sections. Impedance analysis was used for
      localization of alendronate-induced effects on ion transport. Luminal, but not
      serosal, alendronate (pH 6.9-7.2), increased PD and I(sc) in a dose- and time
      dependent manner, with little change in R and mild edema of surface cell layers.
      The changes in I(sc) (and PD) were reversible with drug washout and could be
      prevented either by inhibition of Na,K-ATPase activity with serosal ouabain or by
      inhibition of apical Na channels with luminal acidification to pH 2.0 with HCl.
      An effect on apical Na channel activity was also supported by impedance analysis.
      Luminal alendronate at acidic pH was more damaging than either alendronate at
      neutral pH or acidic pH alone. These data suggest that alendronate stimulates net
      ion (Na) transport in esophageal epithelium by increasing apical membrane sodium
      channel activity and that this occurs with limited morphological change and no
      alteration in barrier function. Also alendronate is far more damaging at acidic
      than at neutral pH, suggesting its association with esophagitis requires gastric
      acid for expression. This expression may occur either by potentiation between the
      damaging effects of (refluxed) gastric acid and drug or by acid-induced
      conversion of the drug to a more toxic form.

PMID- 12181171
TI  - Endothelial COX-1 and -2 differentially affect reactivity of MVB in portal
      hypertensive rats.
AB  - Expression of constitutive and inducible cyclooxygenase (COX-1 and COX-2,
      respectively) and the role of prostanoids were investigated in the aorta and
      mesenteric vascular bed (MVB) from the portal vein-ligated rat (PVL) as a model
      of portal hypertension. Functional experiments were carried out in MVB from PVL
      and sham-operated rats in the absence or presence of the nonselective COX
      inhibitor indomethacin or the selective inhibitors of COX-1 (SC-560) or COX-2 (NS
      398). Western blots of COX-1 and COX-2 proteins were evaluated in aorta and MVB,
      and PGI(2) production by enzyme immunoassay of 6-keto-PGF(1alpha) was evaluated
      in the aorta. In the presence of functional endothelium, decreased contraction to
      norepinephrine (NE) and increased vasodilatation to ACh were observed in MVB from
      PVL. Exposure of MVB to indomethacin, SC-560, or NS-398 reversed the
      hyporeactivity to NE and the increased endothelial vasodilatation to ACh in PVL,
      with NS-398 being more potent than the other two inhibitors. Upregulation of COX
      1 and COX-2 expressions was detected in aorta and MVB from PVL portal
      hypertensive rats, and increased production of 6-keto-PGF(1alpha) was observed in
      aorta from portal hypertensive rats. These results suggest that generation of
      endothelial vasodilator prostanoids, from COX-1 and COX-2 isoforms, accounts for
      the increased mesenteric blood flow in portal hypertension.

PMID- 12181172
TI  - Local, exendin-(9-39)-insensitive, site of action of GLP-1 in canine ileum.
AB  - Glucagon-like peptide-1 (GLP-1) modulates glucose levels following a meal,
      including by inhibition of gastric emptying and intestinal transport. Intra
      arterial injection of GLP-1 into the gastric corpus, antrum, or pylorus of
      anesthetized dogs had no effect on the contractile activity of the resting or
      neurally activated stomach. GLP-1 injected intra-arterially inhibited intestinal
      segments when activated by enteric nerve stimulation but not by acetylcholine.
      Isolated ileum segments were perfused intra-arterially, instrumented with strain
      gauges to record circular muscle activity and with subserosal electrodes to
      stimulate enteric nerves. GLP-1 caused concentration-dependent inhibition of
      nerve-stimulated phasic but not tonic activity. This was absent during TTX
      induced activity and partly prevented by N(G)-nitro-L-arginine. Exendin-(9-39),
      the GLP-1 antagonist, had no intrinsic activity and did not affect the actions of
      GLP-1. Capsaicin mimicked the effects of GLP-1 and may have reduced the effect of
      subsequent GLP-1. GLP-1 may mediate paracrine action on afferent nerves in the
      canine ileal mucosa using an unusual receptor.

PMID- 12181173
TI  - Histamine is involved in gastric vasodilation during acid back diffusion via
      activation of sensory neurons.
AB  - Protective vasodilation during acid back diffusion into the rat gastric mucosa
      depends on activation of sensory neurons and mast cell degranulation with
      histamine release. We hypothesized that these two mediator systems interact and
      that histamine partly exerts its effect via sensory nerves. Gastric blood flow
      (GBF) and luminal histamine were measured in chambered stomachs, and mast cell
      numbers were assessed by morphometry. Ablation of sensory neurons and depletion
      of mast cells were produced by pretreatment with capsaicin or dexamethasone,
      respectively. Mucosal exposure to 1.5 M NaCl and then to pH 1.0 saline in ablated
      and control rats caused increased luminal histamine and reduced numbers of mast
      cells. Enterochromaffin-like cell marker pancreastatin remained unchanged. Only
      control rats responded with an increase in GBF. Capsaicin stimulation (640
      microM) of the undamaged mucosa induced identical increase in GBF and unchanged
      mast cell mass in normal and dexamethasone-treated rats. Increase in GBF after
      topical exposure to histamine (30 mM) in rats pretreated with capsaicin or a
      calcitonin gene-related peptide (CGRP)(1) antagonist human CGRP(8-37) or exposed
      to the calcium pore blocker ruthenium red was less than one-half of that in
      control rats. These data suggest that mast cell-derived histamine is involved in
      gastric vasodilatation during acid back diffusion partly via sensory neurons.

PMID- 12181174
TI  - Cosensitivity of vagal mucosal afferents to histamine and 5-HT in the rat
      jejunum.
AB  - A complex sensitivity of afferent nerves in the mesentery of the rat jejunum to
      systemic administration of histamine has recently been demonstrated. In the
      present study, we aimed to characterize subpopulations of mesenteric afferents
      that mediate this afferent nerve response. Multiunit afferent discharge was
      recorded from mesenteric nerves supplying the proximal jejunum in anesthetized
      rats. The majority of mesenteric bundles (84%) exhibited biphasic responses to
      histamine (8 micromol/kg), and these bundles also responded to 2-methyl-5-HT
      (2m5HT). In contrast, monophasic responses lacked a short-latency component, and
      these bundles failed to respond to 2m5HT. Single-unit analysis revealed a
      population of afferents that possessed cosensitivity for 2m5HT and histamine.
      This population of afferents was absent in chronically vagotomized animals,
      whereas mucosal anesthesia with luminal lidocaine reversibly converted the
      biphasic profile to a monophasic one. Ondansetron (500 microg/kg) blocked the
      response to 2m5HT with no effect on the profile of the histamine response,
      whereas pyrilamine (5 mg/kg) blocked the histamine response without affecting the
      response to 2m5HT. We conclude that histamine-sensitive afferents exist in the
      rat proximal jejunum that also respond to 5-HT via the 5-HT3 receptor. These
      fibers appear to be vagal afferents originating in the intestinal mucosa and may
      be involved in the organization of mast cell-mediated responses.

PMID- 12181175
TI  - Vitamin D-inducible calcium transport and gene expression in three Caco-2 cell
      lines.
AB  - The parental cell line (P) of Caco-2 cells and two clones, BBe and TC7, were
      studied at 11 days postconfluence to test the facilitated diffusion model of
      vitamin D-mediated intestinal calcium absorption (CaTx). Nuclear vitamin D
      receptor (nVDR) and calbindin D(9k) (CaBP) were measured by Western blot; 1,25
      hydroxyvitamin D(3) 24-hydroxylase (CYP24), CaBP, plasma membrane Ca-ATPase
      (PMCA), and Ca transport channel (CaT1) mRNA levels were examined by RT-PCR; and
      net apical-to-basolateral CaTx was examined after treating cells with vehicle or
      10 nM calcitriol for 8 (mRNA levels) or 48 h (protein, CaBP mRNA, CaTx). nVDR
      level was lowest in BBe (38% P value) and directly related to CYP24 induction
      (TC7 = P, which were 1.56 times greater than BBe). nVDR was inversely related to
      the vitamin D-induced levels of CaT1 mRNA, CaBP mRNA, PMCA mRNA, and net CaTx,
      with the highest induction seen in BBe. Basal CaBP mRNA (86 times greater than P)
      and protein levels were highest in TC7 cells and were not associated with higher
      net CaTx, suggesting CaBP may not be rate limiting for CaTx in these cells.

PMID- 12181176
TI  - Modulation of Cl-/OH- exchange activity in Caco-2 cells by nitric oxide.
AB  - The present studies were undertaken to determine the direct effects of nitric
      oxide (NO) released from an exogenous donor, S-nitroso-N-acetyl pencillamine
      (SNAP) on Cl-/OH- exchange activity in human Caco-2 cells. Our results
      demonstrate that NO inhibits Cl-/OH- exchange activity in Caco-2 cells via cGMP
      dependent protein kinases G (PKG) and C (PKC) signal-transduction pathways. Our
      data in support of this conclusion can be outlined as follows: 1) incubation of
      Caco-2 cells with SNAP (500 microM) for 30 min resulted in approximately 50%
      inhibition of DIDS-sensitive 36Cl uptake; 2) soluble guanylate cyclase inhibitors
      Ly-83583 and (1,2,4)oxadiazolo(4,3-a)quinoxalin-1-one significantly blocked the
      inhibition of Cl-/OH- exchange activity by SNAP; 3) addition of 8-bromo-cGMP (8
      BrcGMP) mimicked the effects of SNAP; 4) specific PKG inhibitor KT-5823
      significantly inhibited the decrease in Cl-/OH- exchange activity in response to
      either SNAP or 8-BrcGMP; 5) Cl-/OH-exchange activity in Caco-2 cells in response
      to SNAP was not altered in the presence of protein kinase A (PKA) inhibitor (Rp
      cAMPS), demonstrating that the PKA pathway was not involved; 6) the effect of NO
      on Cl-/OH- exchange activity was mediated by PKC, because each of the two PKC
      inhibitors chelerythrine chloride and calphostin C blocked the SNAP-mediated
      inhibition of Cl-/OH- exchange activity; 7) SO/OH- exchange in Caco-2 cells was
      unaffected by SNAP. Our results suggest that NO-induced inhibition of Cl-/OH-
      exchange may play an important role in the pathophysiology of diarrhea associated
      with inflammatory bowel diseases.

PMID- 12181177
TI  - LPS-induced suppression of gastric motility relieved by TNFR:Fc construct in
      dorsal vagal complex.
AB  - Our previous studies suggested that the cytokine tumor necrosis factor-alpha (TNF
      alpha) may act within the neural circuitry of the medullary dorsal vagal complex
      (DVC) to affect changes in gastric function, such as gastric stasis, loss of
      appetite, nausea, and vomiting. The definitive demonstration that endogenously
      generated TNF-alpha is capable of affecting gastric function via the DVC
      circuitry has been impeded by the lack of an antagonist for TNF-alpha. The
      present studies used localized central nervous system applications of the TNF
      adsorbant construct (TNFR:Fc; TNF-receptor linked to the Fc portion of the human
      immunoglobulin IgG1) to attempt to neutralize the suppressive effects of
      endogenously produced TNF-alpha. Gastric motility of thiobutabarbital
      anesthetized rats was monitored after systemic administration of
      lipopolysaccharide (LPS) to induce TNF-alpha production. Continuous perfusion of
      the floor of the fourth ventricle with TNFR:Fc reversed the potent
      gastroinhibition induced by LPS, i.e., central thyrotropin-releasing hormone
      induced increases in motility were not inhibited. This disinhibition of gastric
      stasis was not seen after intravenous administration of similar doses of TNFR:Fc
      nor ventricular application of the Fc fragment of human immunoglobulin. These
      results validate our previous studies that suggest that circulating TNF-alpha may
      act directly within the DVC to affect gastric function in a variety of
      pathophysiological states.

PMID- 12181178
TI  - Activation of human and mouse Kupffer cells by lipopolysaccharide is mediated by
      CD14.
AB  - Upregulation of CD14 in Kupffer cells has been implicated in the pathogenesis of
      several forms of liver injury, including alcoholic liver disease. However, it
      remains unclear whether CD14 mediates lipopolysaccharide (LPS) signaling in this
      specialized liver macrophage population. In this series of experiments, we
      determined the role of CD14 in LPS activation of Kupffer cells by using several
      complementary approaches. First, we isolated Kupffer cells from human livers and
      studied the effects of anti-CD14 antibodies on LPS activation of these cells.
      Kupffer cells were incubated with increasing concentrations of LPS in the
      presence and absence of recombinant human LPS binding protein (LBP). With
      increasing concentrations of LPS, human Kupffer cell tumor necrosis factor-alpha
      (TNF-alpha) production (a marker for Kupffer cell activation) increased in a dose
      dependent manner in the presence and absence of LBP. In the presence of anti
      human CD14 antibodies, the production of TNF-alpha was significantly diminished.
      Second, we compared LPS activation of Kupffer cells isolated from wild-type and
      CD14 knockout mice. Kupffer cells from CD14 knockout mice produced significantly
      less TNF-alpha in response to the same amount of LPS. Together, these data
      strongly support a critical role for CD14 in Kupffer cell responses to LPS.

PMID- 12181180
TI  - Mesenteric afferent nerves are sensitive to vascular perfusion in a novel
      preparation of rat ileum in vitro.
AB  - Using novel in vitro preparations of vascularly perfused rat ileum, we
      investigated mesenteric afferent sensitivity to vascular perfusion. Gut (GPP) and
      vascular (VPP) perfusion pressures were recorded simultaneously with afferent
      discharge (AD). After preconstriction (L-phenylephrine), capsaicin (100 microM,
      gut lumen) caused a transient increase in AD and a sustained fall in VPP,
      supporting afferent modulation of vascular tone. In turn, AD was affected by
      vascular perfusion rate (VPR). Increasing VPR step-wise (0.6 to 1.0, 1.4 and 1.8
      ml/min) caused concomitant falls in AD, returning at 0.6 ml/min. Terminating flow
      (5 min) increased AD. Afferent responses were independent of changes in GPP,
      vascular O2, or the gut "tube" ("gut-off"). In gut-off studies, where capsaicin
      (100 nM ia) still reduced VPP, flow-associated falls in AD were abolished by the
      enzyme neuraminidase (0.2 U/ml ia or extravascularly over 20 min). In contrast,
      increased AD after stopped flow was unaffected. We propose that mesenteric
      afferents "sense" changes in vascular perfusion. The precise stimuli (pressure
      and/or flow) and the physiological relevance to control of local circulation
      remain to be determined.

PMID- 12181179
TI  - Sexual dimorphic expression of ADH in rat liver: importance of the hypothalamic
      pituitary-liver axis.
AB  - Hepatic alcohol dehydrogenase (ADH) activity is higher in female than in male
      rats. Although sex steroids, thyroid, and growth hormone (GH) have been shown to
      regulate hepatic ADH, the mechanism(s) for sexual dimorphic expression is
      unclear. We tested the possibility that the GH secretory pattern determined
      differential expression of ADH. Gonadectomized and hypophysectomized male and
      female rats were examined. Hepatic ADH activity was 2.1-fold greater in females.
      Because protein and mRNA content were also 1.7- and 2.4-fold greater, results
      indicated that activity differences were due to pretranslational mechanisms.
      Estradiol increased ADH selectively in males, and testosterone selectively
      decreased activity and mRNA levels in females. Effect of sex steroids on ADH was
      lost after hypophysectomy; infusion of GH in males increased ADH to basal female
      levels, supporting a role of the pituitary-liver axis. However, GH and L
      thyroxine (T4) replacements alone in hypophysectomized rats did not restore
      dimorphic differences for either ADH activity or mRNA levels. On the other hand,
      T4 in combination with intermittent administration of GH reduced ADH activity and
      mRNA to basal male values, whereas T4 plus GH infusion replicated female levels.
      These results indicate that the intermittent male pattern of GH secretion
      combined with T4 is the principal determinant of low ADH activity in male liver.

PMID- 12181181
TI  - Models of gastric hyperalgesia in the rat.
AB  - Despite the prevalence of dyspepsia, nonhuman models for study of gastric
      hyperalgesia are limited. We thus characterized responses to gastric distension
      (GD) in the absence of and after two different gastric insults. A balloon was
      surgically placed into the stomach, and electromyographic responses to GD were
      recorded from the acromiotrapezius muscle at various times after balloon
      placement. Rats received either 20% acetic acid (HAc) or saline injections into
      the stomach wall or 0.1% iodoacetamide (IA) in drinking water. Responses to GD
      were monotonic with increasing distending pressure (10-80 mmHg) and were
      reproducible from days 3-14 after balloon implantation. Both HAc injection and IA
      ingestion led to increased responses to GD (i.e., gastric hyperalgesia), which,
      in the case of HAc, persisted for 60 days after HAc treatment. HAc injection
      produced ulcers in all treated animals; IA ingestion produced no lesions.
      Myeloperoxidase activity significantly increased after HAc but not saline
      injection or IA ingestion. In the awake, unrestrained rat, visceromotor responses
      to GD are quantifiable, reliable, and reproducible. Significantly enhanced
      responses to GD were apparent in two models of gastric insult, both of which may
      be useful for the study of the mechanisms of gastric hyperalgesia.

PMID- 12181182
TI  - Effect of prolonged gastric distension on motor function of LES and of proximal
      stomach.
AB  - Gastric distension is a potent stimulus of transient lower esophageal sphincter
      (LES) relaxation. To investigate the time effect of prolonged gastric distension
      on the rate of transient LES relaxations, LES pressure, and the motor and sensory
      functions of the proximal stomach, we performed a continuous isobaric distension
      of the proximal stomach at the 75% threshold pressure for discomfort for 2 h in
      seven healthy subjects. A multilumen assembly incorporating a sleeve and an
      electronic barostat was used. The rate of transient LES relaxations (n/30 min)
      was constant during the first hour [4.1 +/- 1.2 (0-30 min) and 5.4 +/- 1.1 (30-60
      min)] but markedly decreased (P < 0.05) in the second hour [2.1 +/- 0.5 (60-90
      min) and 2.3 +/- 0.9 (90-120 min)], whereas LES pressure, baseline volume and
      volume waves within the gastric bag, hunger, and fullness did not change
      throughout the experiment. It is concluded that the rate of transient LES
      relaxations decreases with time during prolonged gastric distension, thus
      suggesting that this type of stimulus should not be used in sequential
      experimental conditions.

PMID- 12181183
TI  - Effect of intragastric barostat bag on proximal and distal gastric accommodation
      in response to liquid meal.
AB  - The barostat is the gold standard for measurement of proximal gastric
      accommodation. Ultrasonography can be used to measure gastric volume. The aim was
      to investigate the effects of the barostat bag on gastric accommodation and
      transpyloric flow. Accommodation after a liquid meal (300 ml, 450 kcal) was
      measured twice at random in eight healthy volunteers. Proximal accommodation was
      measured once using barostat and once using ultrasound (US). Antrum accommodation
      was measured using US. Bag volume (BV), antral area (AA), proximal gastric area,
      and proximal gastric diameter (PGD) data were assessed before and 1, 5, 15, 30,
      40, 50, and 60 min postprandially. Transpyloric flow was measured using Doppler 1
      5 min postprandially. Fasted, AA size was not affected by the barostat bag (1
      mmHg > minimal distension pressure; 2.7 +/- 0.5 vs. 2.6 +/- 0.3 cm(2)).
      Postprandially, AAs were larger with the bag present (ANOVA, P < 0.04). Maximum
      AA was reached with the bag in 5 min, without the bag in 1 min postprandially
      (15.1 +/- 2.3 vs. 9.4 +/- 1.5 cm(2); P < 0.03). Furthermore, AAs were related to
      BVs (r = 0.57; P < 0.01). After bag deflation, AA decreased (11.9 +/- 1.8 to 7.0
      +/- 0.9 cm(2); P = 0.02) and was comparable with the 60-min AA size without the
      bag (7.1 +/- 1.2 cm(2); P = 0.76) present. Proximal gastric radius calculated
      from the BVs and PGDs was larger with the bag present (ANOVA, P < 0.001). No
      effect on early gastric emptying was observed. Postprandially, the barostat bag
      causes dilatation of the antrum due to meal displacement without influencing
      early gastric emptying. This antral dilatation is likely to induce exaggerated
      proximal gastric relaxation observed in studies using the barostat to evaluate
      fundic accommodation.

PMID- 12181184
TI  - Effect of iron status on DMT1 expression in duodenal enterocytes from beta2
      microglobulin knockout mice.
AB  - Divalent metal transporter I (DMT1) is thought to be involved in transport of
      iron across the apical cell membrane of villus duodenal cells. To determine its
      role in hereditary hemochromatosis (HH), we used beta2-microglobulin knockout
      (B2M-/-) mice that accumulate iron as in HH. The B2M-/- and control C57BL/6
      (B2M+/+) mice were fed diets with different iron contents. Increasing the iron
      availability increased plasma iron levels in both B2M+/+ and B2M-/- mice.
      Reducing the iron availability decreased the plasma iron concentration in B2M+/+
      mice but was without effect on plasma iron in B2M-/- mice. DMT1 was not
      detectable in mice fed normal or iron-loaded diets when using
      immunohistochemistry. In Western blots, however, the protein was consistently
      observed regardless of the dietary regimen. DMT1 expression was increased to the
      same extent in B2M+/+ and B2M-/- mice when fed an iron-poor diet. In both strains
      of mice fed an iron-poor diet, DMT1 was evenly distributed in the differentiated
      enterocytes from the base to the tip of the villi but was absent from the crypts
      of Lieberkuhn. These data suggest that the observed effects were due to the state
      of iron deficiency in mucosal cells rather than genetic defect.

PMID- 12181185
TI  - Proguanylin secretion and the role of negative-feedback inhibition in a villous
      epithelial cell line.
AB  - The mechanisms of proguanylin synthesis and secretion in the intestine are
      incompletely understood. We designed an in vitro model to study proguanylin
      secretion in a model of intestinal villous epithelial cells. The C2/bbe1 cell
      line, a differentiated subclone of Caco-2 cells, was used to examine the
      direction of proguanylin secretion and the potential for feedback regulation via
      activators of the guanylyl cyclase C signal transduction pathway. When cells were
      grown on Transwell inserts, proguanylin was secreted into the apical and
      basolateral media, consistent with other models of intestinal guanylin secretion.
      Proguanylin synthesis and secretion were not decreased on activation of guanylyl
      cyclase C-mediated chloride secretion, implying a regulatory system other than
      negative-feedback inhibition. These data describe the use of C2/bbe1 cells as a
      model for proguanylin secretion in villous epithelial cells and demonstrate their
      potential use for the study of the regulatory mechanisms governing proguanylin
      synthesis and secretion.

PMID- 12181186
TI  - Role of TNF-alpha in gut mucosal changes after severe burn.
AB  - Gut epithelial cell death by apoptosis is increased in the gut epithelium after
      severe burn associated with mucosal atrophy. We hypothesized that tumor necrosis
      factor (TNF)-alpha-TNF receptor (TNFR) interaction activates apoptosis in small
      bowel mucosal cells after severe burn. C57BL6 mice received a 30% total body
      surface area scald burn and were treated with neutralizing anti-TNF-alpha. The
      proximal small bowel was assessed for mucosal atrophy. Proliferation and
      apoptosis of mucosal cells were assessed by proliferative cell nuclear antigen
      immunostaining and terminal deoxyuridine nick-end labeling assay, respectively.
      Mucosal height and mucosal cell number decreased after burn. Anti-TNF-alpha
      treated mice showed significantly less mucosal atrophy. Proliferation of
      intestinal cells was not changed with burn or anti-TNF-alpha treatment. An over
      threefold increase in apoptotic cell number was seen after burn, which was
      diminished by anti-TNF-alpha treatment. Changes in gut mucosal homeostasis after
      severe burn are affected, in part, by the activation of apoptosis by TNF-alpha
      TNFR interaction.

PMID- 12181187
TI  - Resistance to Fas-induced apoptosis in hepatocytes: role of GSH depletion by cell
      isolation and culture.
AB  - The involvement of reduction/oxidation (redox) state in cell sensitivity to
      apoptosis has been suggested by several studies in which induction of apoptosis
      was shown to require oxidative stress or GSH extrusion. On the other hand,
      biochemical studies of caspases revealed that their activation necessitates a
      reduced cysteine in their active site. This is ensured by maintaining intact
      intracellular glutathione status during apoptotic induction as reported by in
      vivo studies. Therefore, we investigated the relationship between intracellular
      glutathione levels and the sensitivity of mouse hepatocytes in culture to Fas
      induced apoptosis as well as potential mechanisms responsible for this
      sensitivity. We found that total and reduced glutathione levels are decreased by
      one-half after cell isolation procedure and further decline by 25% during cell
      culture for 2 h in normal Williams' E medium. Cell culture in medium supplemented
      with cysteine and methionine maintains glutathione at a level similar to that
      measured just after cell isolation. Results show that the capacity of Fas to
      activate caspase-8 and to induce apoptosis requires important intracellular
      glutathione levels and high GSH/total glutathione ratio. In conclusion, the
      present study shows that intracellular glutathione plays an important role in
      maintaining the apoptotic machinery functional and is thus capable of
      transmitting the apoptotic signal.

PMID- 12181188
TI  - Iron activates NF-kappaB in Kupffer cells.
AB  - Iron exacerbates various types of liver injury in which nuclear factor (NF)
      kappaB-driven genes are implicated. This study tested a hypothesis that iron
      directly elicits the signaling required for activation of NF-kappaB and
      stimulation of tumor necrosis factor (TNF)-alpha gene expression in Kupffer
      cells. Addition of Fe2+ but not Fe3+ (approximately 5-50 microM) to cultured rat
      Kupffer cells increased TNF-alpha release and TNF-alpha promoter activity in a NF
      kappaB-dependent manner. Cu+ but not Cu2+ stimulated TNF-alpha protein release
      and promoter activity but with less potency. Fe2+ caused a disappearance of the
      cytosolic inhibitor kappaBalpha, a concomitant increase in nuclear p65 protein,
      and increased DNA binding of p50/p50 and p65/p50 without affecting activator
      protein-1 binding. Addition of Fe2+ to the cells resulted in an increase in
      electron paramagnetic resonance-detectable.OH peaking at 15 min, preceding
      activation of NF-kappaB but coinciding with activation of inhibitor kappaB kinase
      (IKK) but not c-Jun NH2-terminal kinase. In conclusion, Fe2+ serves as a direct
      agonist to activate IKK, NF-kappaB, and TNF-alpha promoter activity and to induce
      the release of TNF-alpha protein by cultured Kupffer cells in a redox status
      dependent manner. We propose that this finding offers a molecular basis for iron
      mediated accentuation of TNF-alpha-dependent liver injury.

PMID- 12181189
TI  - cAMP inhibits bile acid-induced apoptosis by blocking caspase activation and
      cytochrome c release.
AB  - We have previously shown that cAMP protects against bile acid-induced apoptosis
      in cultured rat hepatocytes in a phosphoinositide 3-kinase (PI3K)-dependent
      manner. In the present studies, we investigated the mechanisms involved in this
      anti-apoptotic effect. Hepatocyte apoptosis induced by glycodeoxycholate (GCDC)
      was associated with mitochondrial depolarization, activation of caspases, the
      release of cytochrome c from the mitochondria, and translocation of BAX from the
      cytosol to the mitochondria. cAMP inhibited GCDC-induced apoptosis, caspase 3 and
      caspase 9 activation, and cytochrome c release in a PI3K-dependent manner. cAMP
      activated PI3K in p85 immunoprecipitates and resulted in PI3K-dependent
      activation of the survival kinase Akt. Chemical inhibition of Akt phosphorylation
      with SB-203580 partially blocked the protective effect of cAMP. cAMP resulted in
      wortmannin-independent phosphorylation of BAD and was associated with
      translocation of BAD from the mitochondria to the cytosol. These results suggest
      that GCDC-induced apoptosis in cultured rat hepatocytes proceeds through a
      caspase-dependent intracellular stress pathway and that the survival effect of
      cAMP is mediated in part by PI3K-dependent Akt activation at the level of the
      mitochondria.

PMID- 12181190
TI  - Unimpaired osmotic water permeability and fluid secretion in bile duct epithelia
      of AQP1 null mice.
AB  - The mechanisms by which fluid moves across the luminal membrane of cholangiocyte
      epithelia are uncertain. Previous studies suggested that aquaporin-1 (AQP1) is an
      important determinant of water movement in rat cholangiocytes and that cyclic AMP
      mediates the movement of these water channels from cytoplasm to apical membrane,
      thereby increasing the osmotic water permeability. To test this possibility we
      measured agonist-stimulated fluid secretion and osmotically driven water
      transport in isolated bile duct units (IBDUs) from AQP1 wild-type (+/+) and null
      (-/-) mice. AQP1 expression was confirmed in a mouse cholangiocyte cell line and
      +/+ liver. Forskolin-induced fluid secretion, measured from the kinetics of IBDU
      luminal expansion, was 0.05 fl/min and was not impaired in -/- mice. Osmotic
      water permeability (P(f)), measured from the initial rate of IBDU swelling in
      response to a 70-mosM osmotic gradient, was 11.1 x 10(-4) cm/s in +/+ mice and
      11.5 x 10(-4) cm/s in -/- mice. P(f) values increased by approximately 50% in
      both +/+ and -/- mice following preincubation with forskolin. These findings
      provide direct evidence that AQP1 is not rate limiting for water movement in
      mouse cholangiocytes and does not appear to be regulated by cyclic AMP in this
      species.

PMID- 12181191
TI  - Regulation of NHE3 by nitric oxide in Caco-2 cells.
AB  - The effect of nitric oxide (NO) on Na+/H+ exchange (NHE) activity was
      investigated utilizing Caco-2 cells as an experimental model. Incubation of Caco
      2 cells with 10(-3) M S-nitroso-N-acetylpenicillamine (SNAP), a conventional
      donor of NO, for 20 min resulted in a approximately 45% dose-dependent decrease
      in NHE activity, as determined by assay of ethylisopropylamiloride-sensitive 22Na
      uptake. A similar decrease in NHE activity was observed utilizing another NO
      specific donor, sodium nitroprusside. SNAP-mediated inhibition of NHE activity
      was not secondary to a loss of cell viability. NHE3 activity was significantly
      reduced by SNAP (P < 0.05), whereas NHE2 activity was essentially unaltered. The
      effects of SNAP were mediated by the cGMP-dependent signal transduction pathway
      as follows: 1) LY-83583 and 1H-(1,2,4)oxadiazolo(4,3-a)quinoxalin-1-one (ODQ),
      specific inhibitors of soluble guanylate cyclase, blocked the inhibitory effect
      of SNAP on NHE; 2) 8-bromo-cGMP mimicked the effects of SNAP on NHE activity; 3)
      the SNAP-induced decrease in NHE activity was counteracted by a specific protein
      kinase G inhibitor, KT-5823 (1 microM); 4) chelerythrine chloride (2 microM) or
      calphostin C (200 nM), specific protein kinase C inhibitors, did not affect
      inhibition of NHE activity by SNAP; 5) there was no cross activation by the
      protein kinase A-dependent pathway, as the inhibitory effects of SNAP were not
      blocked by Rp-cAMPS (25 microM), a specific protein kinase A inhibitor. These
      data provide novel evidence that NO inhibits NHE3 activity via activation of
      soluble guanylate cyclase, resulting in an increase in intracellular cGMP levels
      and activation of protein kinase G.

PMID- 12181192
TI  - Expression of rat hepatic multidrug resistance-associated proteins and organic
      anion transporters in pregnancy.
AB  - The expression of hepatic multidrug resistance-associated protein (Mrp)1, 2, 3,
      and 6 and organic anion transporting polypeptides (Oatp)1 and 2 were examined in
      control and 20- to 21-day pregnant rats. Western analysis showed that expression
      of Oatp2 was decreased 50% in pregnancy, whereas expression of Oatp1 did not
      change. Expression of Mrp2 protein determined by Western analysis of total liver
      homogenate decreased to 50% of control levels in pregnant rats, consistent with
      studies using plasma membranes. Confocal immunohistochemistry showed that Mrp2
      expression was confined to the canalicular membrane in both control and pregnant
      rats and was not detectable in intracellular compartments. In isolated perfused
      liver, the biliary excretion of 2,4-dintrophenyl-glutathione was significantly
      decreased in pregnancy, consistent with decreased expression of Mrp2. The
      expression of the basolateral transporter Mrp1 was not altered in pregnancy,
      whereas expression of Mrp6 mRNA was decreased by 60%. Expression of Mrp3 was also
      decreased by 50% in pregnant rat liver, indicating differential regulation of Mrp
      isoforms in pregnancy. These data also demonstrate that decreased Mrp2 expression
      is not necessarily accompanied by increased Mrp3 expression.

PMID- 12181194
TI  - Similarities and differences in the propagation of slow waves and peristaltic
      waves.
AB  - The relationship between slow waves and peristaltic reflexes has not been well
      analyzed. In this study, we have recorded the electrical activity of slow waves
      together with that generated by spontaneous peristaltic contractions at 240
      extracellular sites simultaneously. Recordings were made from five isolated
      tubular and six sheet segments of feline duodenum superfused in vitro. In all
      preparations, slow waves propagated as broad wave fronts along the longitudinal
      axis of the preparation in either the aborad or the orad direction. Electrical
      potentials recorded during peristalsis (peristaltic waves) also propagated as
      broad wave fronts in either directions. Peristaltic waves often spontaneously
      stopped conducting (46%), in contrast to slow waves that never did. Peristaltic
      waves propagated at a lower velocity than the slow waves (0.98 +/- 0.25 and 1.29
      +/- 0.28 cm/s, respectively; P < 0.001; n = 24) and in a direction independent of
      the preceding slow wave direction (64% in the same direction, 46% in the opposite
      direction). In conclusion, slow waves and peristaltic waves in the isolated
      feline duodenum seem to constitute two separate electrical events that may drive
      two different mechanisms of contraction in the small intestine.

PMID- 12181193
TI  - Multipotential stem cells in adult mouse gastric epithelium.
AB  - Previous studies of chimeric animals demonstrate that multipotential stem cells
      play a role in the development of the gastric epithelium; however, despite much
      effort, it is not clear whether they persist into adulthood. Here, chemical
      mutagenesis was used to label random epithelial cells by loss of transgene
      function in adult hemizygous ROSA26 mice, a mouse strain expressing the transgene
      lacZ in all tissues. Many clones derived from such cells contained all the major
      epithelial cell types, thereby demonstrating existence of functional
      multipotential stem cells in adult mouse gastric epithelium. We also observed
      clones containing only a single mature cell type, indicating the presence of long
      lived committed progenitors in the gastric epithelium. Similar results were
      obtained in duodenum and colon, showing that this mouse model is suitable for
      lineage tracing in all regions of the gastrointestinal tract and likely useful
      for cell lineage studies in other adult renewing tissues.

PMID- 12181195
TI  - Regulation of parietal cell migration by gastrin in the mouse.
AB  - Recent studies suggest that gastrin regulates parietal cell maturation. We asked
      whether it also regulates parietal cell life span and migration along the gland.
      Dividing cells were labeled with 5'-bromo-2'-deoxyuridine (BrdU), and parietal
      cells were identified by staining with Dolichos biflorus lectin. Cells positive
      for D. biflorus lectin and BrdU were reliably identified 10-30 days after BrdU
      injection in mice in which the gastrin gene had been deleted by homologous
      recombination (Gas-KO) and wild-type (C57BL/6) mice. The time course of labeling
      was similar in the two groups. The distribution of BrdU-labeled parietal cells in
      wild-type mice was consistent with migration to the base of the gland, but in Gas
      KO mice, a higher proportion of BrdU-labeled cells was found more superficially
      20 and 30 days after BrdU injection. Conversely, in transgenic mice
      overexpressing gastrin, BrdU-labeled parietal cells accounted for a higher
      proportion of the labeled pool in the base of the gland 10 days after BrdU
      injection. Gastrin, therefore, stimulates movement of parietal cells along the
      gland axis but does not influence their life span.

PMID- 12181196
TI  - Cathepsin B inhibition prevents trypsinogen activation and reduces pancreatitis
      severity.
AB  - Intrapancreatic activation of trypsinogen is believed to play a critical role in
      the initiation of acute pancreatitis, but mechanisms responsible for
      intrapancreatic trypsinogen activation during pancreatitis have not been clearly
      defined. In previous in vitro studies, we have shown that intra-acinar cell
      activation of trypsinogen and acinar cell injury in response to supramaximal
      secretagogue stimulation could be prevented by the cell permeant cathepsin B
      inhibitor E64d (Saluja A, Donovan EA, Yamanaka K, Yamaguchi Y, Hofbauer B, and
      Steer ML. Gastroenterology 113: 304-310, 1997). The present studies evaluated the
      role of intrapancreatic trypsinogen activation, this time under in vivo
      conditions, in two models of pancreatitis by using another highly soluble cell
      permeant cathepsin B inhibitor, L-3-trans-(propylcarbamoyl)oxirane-2-carbonyl-L
      isoleucyl-L-proline methyl ester (CA-074me). Intravenous administration of CA
      074me (10 mg/kg) before induction of either secretagogue-elicited pancreatitis in
      mice or duct infusion-elicited pancreatitis in rats markedly reduced the extent
      of intrapancreatic trypsinogen activation and substantially reduced the severity
      of both pancreatitis models. These observations support the hypothesis that,
      during the early stages of pancreatitis, trypsinogen activation in the pancreas
      is mediated by the lysosomal enzyme cathepsin B. Our findings also suggest that
      pharmacological interventions that inhibit cathepsin B may prove useful in
      preventing acute pancreatitis or reducing its severity.

PMID- 12181197
TI  - Proapoptotic protein PACT is expressed at high levels in colonic epithelial cells
      in mice.
AB  - The protein activator of RNA-activated protein kinase (PKR) is a proapoptotic
      protein called PACT. PKR is an interferon (IFN)-induced serine-threonine protein
      kinase that plays a central role in IFN's antiviral and antiproliferative
      activities. PKR activation in cells leads to phosphorylation of the alpha-subunit
      of the eukaryotic protein synthesis initiation factor (eIF)2alpha, inhibition of
      protein synthesis, and apoptosis. In the absence of viral infections, PKR is
      activated by its activator PACT, especially in response to diverse stress
      signals. Overexpression of PACT in cells causes enhanced sensitivity to stress
      induced apoptosis. We examined PACT expression in different mouse tissues and
      evaluated its possible role in regulating apoptosis. PACT is expressed at high
      levels in colonic epithelial cells, especially as they exit the cell cycle and
      enter an apoptotic program. PACT expression also coincides with the presence of
      active PKR and phosphorylated eIF2alpha. These results suggest a possible role of
      PACT-mediated PKR activation in the regulation of epithelial cell apoptosis in
      mouse colon. In addition, transient overexpression of PACT in a nontransformed
      intestinal epithelial cell line leads to induction of apoptosis, further
      supporting PACT's role in inducing apoptosis.

PMID- 12181198
TI  - IGF-I and TGF-beta1 have distinct effects on phenotype and proliferation of
      intestinal fibroblasts.
AB  - Insulin-like growth factor I (IGF-I) and transforming growth factor-beta1 (TGF
      beta1) are upregulated in myofibroblasts at sites of fibrosis in experimental
      enterocolitis and in Crohn's disease (CD). We compared the sites of expression of
      IGF-I and TGF-beta1 in a rat peptidoglycan-polysaccharide (PG-PS) model of
      chronic granulomatous enterocolitis and fibrosis. We used the human colonic CCD
      18Co fibroblast/myofibroblast cell line to test the hypothesis that TGF-beta1 and
      IGF-I interact to regulate proliferation, collagen synthesis, and activated
      phenotype typified by expression of alpha-smooth muscle actin and organization
      into stress fibers. IGF-I potently stimulated while TGF-beta1 inhibited basal DNA
      synthesis. TGF-beta1 and IGF-I each had similar but not additive effects to
      induce type I collagen. TGF-beta1 but not IGF-I potently stimulated expression of
      alpha-smooth muscle actin and stress fiber formation. IGF-I in combination with
      TGF-beta1 attenuated stress fiber formation without reducing alpha-smooth muscle
      actin expression. Stress fibers were not a prerequisite for increased collagen
      synthesis. TGF-beta1 upregulated IGF-I mRNA, which led us to examine the effects
      of IGF-I in cells previously activated by TGF-beta1 pretreatment. IGF-I potently
      stimulated proliferation of TGF-beta1-activated myofibroblasts without reversing
      activated fibrogenic phenotype. We conclude that TGF-beta1 and IGF-I both
      stimulate type I collagen synthesis but have differential effects on activated
      phenotype and proliferation. We propose that during intestinal inflammation,
      regulation of activated phenotype and proliferation may require sequential
      actions of TGF-beta1 and IGF-I, but they may act in concert to increase collagen
      deposition.

PMID- 12181199
TI  - Apoptosis in activated rat pancreatic stellate cells.
AB  - Proliferation and matrix synthesis by activated pancreatic stellate cells (PSC)
      participate in the development of chronic pancreatitis. Apoptosis of PSC may
      terminate this process but has not yet been studied in this particular cell type
      and was the aim of the present study. PSC were isolated from rat pancreas and
      characterized for expression of glial fibrillary acidic protein, alpha-smooth
      muscle actin, CD95, and tumor necrosis factor-alpha-related apoptosis-inducing
      ligand (TRAIL) receptors. Apoptosis was determined by TdT-UTP nick end-labeling
      reaction, annexin V binding, and caspase-8 activation. Both CD95L and TRAIL
      induced apoptosis in PSC. The apoptotic response was minor in PSC cultured for 7
      days but increased markedly thereafter. Sensitization of PSC with culture
      duration was accompanied by increased expression of CD95 and TRAIL receptor 2 and
      no alterations of Flip expression or protein kinase B phosphorylation but was
      paralleled by the appearance of a COOH-terminal cleavage product of receptor
      interacting protein. PSC apoptosis was also induced by PK-11195, a ligand of the
      peripheral benzodiazepine receptor. PSC apoptosis may be important in terminating
      the wound-healing response after pancreas injury and exhibits features distinct
      from apoptosis induction in hepatic stellate cells.

PMID- 12181200
TI  - Grown-up congenital heart (GUCH) disease: current needs and provision of service
      for adolescents and adults with congenital heart disease in the UK.
AB  - This report addresses the needs and problems of grown-up congenital heart (GUCH)
      patients and makes recommendations on organisation of national medical care,
      training of specialists, and education of the profession. The size of the
      national population of patients with grown-up congenital heart disease (GUCH) is
      uncertain, but since 80-85% of patients born with congenital heart disease now
      survive to adulthood (age 16 years), an annual increase of 2500 can be
      anticipated according to birth rate. Organisation of medical care is haphazard
      with only three of 18 cardiac surgical centres operating on over 30 cases per
      annum and only two established specialised units fully equipped and staffed. Not
      all grown-ups with congenital heart disease require the same level of expertise;
      20-25% are complex, rare, etc, and require life long expert supervision and/or
      intervention; a further 35-40% require access to expert consultation. The rest,
      about 40%, have simple or cured diseases and need little or no specialist
      expertise. The size of the population needing expertise is small in comparison to
      coronary and hypertensive disease, aging, and increasing in complexity. It
      requires expert cardiac surgery and specialised medical cardiology, intensive
      care, electrophysiology, imaging and interventions, "at risk" pregnancy services,
      connection to transplant services familiar with their basic problem, clinical
      nurse specialist advisors, and trained nurses. An integrated national service is
      described with 4-6 specialist units established within adult cardiology, ideally
      in relation or proximity to university hospital/departments in appropriate
      geographic location, based in association with established paediatric cardiac
      surgical centres with designated inpatient and outpatient facilities for grown-up
      patients with congenital heart disease. Specialist units should accept
      responsibility for educating the profession, training the specialists,
      cooperative research, receiving patients "out of region", sharing particular
      skills between each other, and they must liaise with other services and trusts in
      the health service, particularly specified outpatient clinics in district and
      regional centres. Not every regional cardiac centre requires a full GUCH
      specialised service since there are too few patients. Complex patients need to be
      concentrated for expertise, experience, and optimal management. Transition of
      care from paediatric to adult supervision should be routine, around age 16 years,
      flexibly managed, smooth, and explained to patient and family. Each patient
      should be entered into a local database and a national registry needs to be
      established. The Department of Health should accept responsibility of
      dissemination of information on special needs of such patients. The GUCH
      Patients' Association is active in helping with lifestyle and social problems.
      Easy access to specialised care for those with complex heart disease is crucial
      if the nation accepts, as it should, continued medical responsibility to provide
      optimal medical care for GUCH patients.

PMID- 12181201
TI  - Imaging of cardiac adrenergic innervation.

PMID- 12181202
TI  - Automated cardiac flow measurement by digital colour Doppler echocardiography.

PMID- 12181203
TI  - Percutaneous coronary intervention in diabetics: time to consider "intimal
      remodelling therapy"?

PMID- 12181204
TI  - Atropa belladonna.

PMID- 12181205
TI  - Difficult haemostasis following diagnostic transfemoral angiogram caused by
      inadvertent puncture of the arteria profunda femoris.

PMID- 12181206
TI  - Papillary fibroelastoma as a cause of cardioembolic stroke.

PMID- 12181207
TI  - Tumour feeding vessel in metastatic intracardiac mass demonstrated by
      transthoracic Doppler echocardiography.

PMID- 12181208
TI  - New insights into the mechanism of neurally mediated syncope.
AB  - OBJECTIVE: To determine the role of the cerebral cortex in neurally mediated
      syncope, the electroencephalograms (EEG) of patients recorded during head up tilt
      table test were analysed. DESIGN: Retrospective study. SETTING: University
      hospital. PATIENTS: 18 patients with syncope or near syncope underwent head up
      tilt table test with simultaneous ECG and EEG monitoring. METHODS: Standard 70
      degrees tilt table test was done with simultaneous ECG and EEG monitoring. EEG
      waveforms were analysed by both visual inspection and spectral analysis. RESULTS:
      6 of 18 patients (33%) had a positive tilt table test. Before syncope slow waves
      increased in patients with a positive test. In addition, five of six tilt
      positive patients (83%) had slow wave activity that lateralised to the left side
      of the brain (mean (SD) 822 (724) v 172 (215) micro V(2), p < 0.05), while none
      of the tilt negative patients exhibited lateralisation (24 (15) v 26 (19) micro
      V(2), NS). Spectral analysis showed that the lateralisation occurred in the delta
      frequency. The lateralisation preceded the event by 5-56 seconds (18 (21)
      seconds). CONCLUSIONS: EEG activity lateralises to the left hemisphere of the
      brain before syncope. The lateralisation precedes syncope and is associated with
      the onset of bradycardia, hypotension, and clinical symptoms. These findings
      suggest that the central nervous system may have a role in neurally mediated
      syncope.

PMID- 12181209
TI  - Prediction of mortality from coronary heart disease among diverse populations: is
      there a common predictive function?
AB  - OBJECTIVES: To examine the generalisability of multivariate risk functions from
      diverse populations in three contexts: ordering risk, magnitude of relative
      risks, and estimation of absolute risk. DESIGN: Meta-analysis of prospective
      cohort studies. PATIENTS: Participants from various epidemiological studies. MAIN
      OUTCOME MEASURE: Death from coronary heart disease (CHD). RESULTS: The analysis
      included 105 420 men and 56 535 women 35-74 years of age and free of CHD at
      baseline from 16 observational studies with a total of 27 analytical groups. The
      area under the receiver operating characteristic curve (AUC) was used to judge
      the ability of the multivariate risk function to order risk correctly. AUCs
      ranged from 0.60 to 0.80. The AUCs differed significantly between the studies (p
      < 0.01) but were very similar for different risk functions applied to the same
      population, indicating similar ability to rank risk for different models. The
      magnitudes of the relative risks associated with major risk factors (age,
      systolic blood pressure, serum total cholesterol, smoking, and diabetes) varied
      significantly across studies (p < 0.05 for homogeneity). The prediction of
      absolute risk was not very accurate in most of the cases when a model derived
      from one study was applied to a different study. CONCLUSIONS: When considered
      qualitatively, the major risk factors are associated with CHD mortality in a
      diverse set of populations. However, when considered quantitatively, there was
      significant heterogeneity in all three aspects: ordering risk, magnitude of
      relative risks, and estimation of absolute risk.

PMID- 12181211
TI  - Magnetic resonance imaging of left atrial thrombus.

PMID- 12181210
TI  - Adherence to statin treatment and readmission of patients after myocardial
      infarction: a six year follow up study.
AB  - OBJECTIVE: To investigate patients' adherence to statin treatment prescribed
      following their first myocardial infarction (MI) and to estimate the effect of
      adherence to statins on recurrence of MI and all cause mortality. DESIGN: Cohort
      study using a record linkage database. SETTING: Tayside, Scotland, UK. PATIENTS:
      Patients who experienced their first MI between January 1990 and November 1995.
      MAIN OUTCOME MEASURES: Percentage of statin use and adherence to statins by
      patients after an MI and the relative risk of hospitalisation for recurrent MI.
      The effect of adherence on all cause mortality was also examined. The covariates
      used were age, sex, socioeconomic deprivation, serum cholesterol concentration,
      diabetes mellitus, cardiovascular drug use, and other hospitalisations. RESULTS:
      Of 5590 patients who experienced an incident MI, 717 (12.8%) experienced at least
      one further MI. Only 7.7% of patients used statins after an MI during the study
      period. Compared with those not taking statins, those who had 80% or better
      adherence to statin treatment had an adjusted relative risk of recurrent MI of
      0.19 (95% confidence interval (CI) 0.08 to 0.47) and all cause mortality of 0.47
      (95% CI 0.22 to 0.99). There was no significant reduction in either end point for
      those who were less than 80% adherent to statins. CONCLUSIONS: Despite the
      infrequent use of statin during the study period, good adherence to statin
      treatment was associated with lower risk of recurrent MI.

PMID- 12181214
TI  - Giant congenital aneurysm of the non-coronary sinus of Valsalva.

PMID- 12181213
TI  - Ventilatory variables are strong prognostic markers in elderly patients with
      heart failure.
AB  - OBJECTIVE: To evaluate the safety and prognostic capacity of cardiopulmonary
      exercise testing in patients > or = 60 years old who are hospitalised with heart
      failure caused by left ventricular dysfunction. DESIGN: Prospective study.
      SETTING: University hospital. PATIENTS: Study participants were 67 patients (66%
      men) with clinical heart failure stabilised on medical treatment. The study is a
      part of a nursing intervention study. Mean (SD) age was 74 (6) years, New York
      Heart Association functional class II-III, and ejection fraction 0.36 (0.11).
      INTERVENTIONS: Cardiopulmonary exercise testing and echocardiography. MAIN
      OUTCOME MEASURES: Peak oxygen consumption (VO2), peak ventilatory equivalents for
      carbon dioxide (VE/VCO2) and oxygen (VE/VO2), left ventricular volumes, and
      mortality. RESULTS: Mean (SD) peak VO2 was 11.7 (3.7) ml/kg/min, peak VE/VCO2 43
      (9), and peak VE/VO2 46 (11). During 12-59 months of follow up, 14 patients died.
      In univariate analyses peak VO2, VE/VO2, and VE/VCO2 were all strongly related (p
      < 0.01) to mortality. In a multivariate Cox regression analysis, peak VE/VCO2 was
      the strongest predictor of mortality (p < 0.001), followed by left ventricular
      end systolic volume (p < 0.001). A cut off of peak VE/VCO2 at > or = 45 gave a
      univariate hazard ratio of 6.7 for death during follow up. No adverse events
      occurred during the exercise test. CONCLUSION: These findings extend results
      found in selected middle aged patients to elderly patients with heart failure and
      show that ventilatory parameters from a cardiopulmonary exercise test, such as
      peak VO2, VE/O2, and VE/VCO2 are powerful predictors of mortality.

PMID- 12181212
TI  - Long term efficacy and safety of atorvastatin in the treatment of severe type III
      and combined dyslipidaemia.
AB  - BACKGROUND: Fibric acid derivatives and HMG-CoA reductase inhibitors are
      effective in combination for treating patients with familial
      dysbetalipoproteinaemia and severe combined dyslipidaemia, but combination
      therapy affects compliance and increases the risk of side effects. AIM: To
      evaluate the efficacy and safety of monotherapy with atorvastatin, an HMG-CoA
      reductase inhibitor with superior efficacy in lowering low density lipoprotein
      cholesterol and triglyceride concentrations, in patients with
      dysbetalipoproteinaemia and severe combined dyslipidaemia. METHODS: Atorvastatin
      was tested as single drug treatment in 36 patients with familial
      dysbetalipoproteinaemia and 23 patients with severe combined dyslipidaemia.
      RESULTS: After 40 weeks of 40 mg atorvastatin treatment decreases in total
      cholesterol, triglycerides, and apolipoprotein B of 40%, 43%, and 41%,
      respectively, were observed in the combined dyslipidaemia group, and of 46%, 40%,
      and 43% in the dysbetalipoproteinaemic patients. Target concentrations of total
      cholesterol (< 5 mmol/l) were reached by 63% of the patients, and target
      concentrations of triglycerides (< 3.0 mmol/l) by 66%. Treatment with
      atorvastatin was well tolerated and no serious side effects were reported.
      CONCLUSIONS: Atorvastatin is very effective as monotherapy in the treatment of
      familial dysbetalipoproteinaemia and severe combined dyslipidaemia.

PMID- 12181215
TI  - Assessment of right ventricular function with Doppler echocardiographic indices
      derived from tricuspid annular motion: comparison with radionuclide angiography.
AB  - OBJECTIVE: To assess right ventricular systolic function using indices derived
      from tricuspid annular motion, and to compare the results with right ventricular
      ejection fraction (RVEF) calculated from radionuclide angiography. DESIGN: Pulsed
      Doppler echocardiography indices were obtained from 10 patients with a normal
      RVEF (group 1) and from 20 patients whose RVEF was less than 45% (group 2).
      RESULTS: The patients in the two groups were similar in age, systolic blood
      pressure, and heart rate. There was a close correlation between the tricuspid
      annular motion derived indices (D wave integral (DWI), peak velocity of D wave
      (PVDW), and tricuspid plane systolic excursion (TPSE)) and RVEF (r = 0.72, 0.82,
      and 0.79, respectively). DWI was significantly higher in group 1 than in group 2.
      PVDW discriminated adequately between individuals with abnormal and normal right
      ventricular ejection fraction. The sensitivity and specificity of tricuspid
      annular motion derived indices were very good. CONCLUSIONS: Indices derived from
      tricuspid annular motion appear to be important tools for assessing right
      ventricular systolic function.

PMID- 12181216
TI  - Clinical characteristics and prognosis of hospitalised inpatients with heart
      failure and preserved or reduced left ventricular ejection fraction.
AB  - OBJECTIVE: To determine the clinical and prognostic differences between patients
      with heart failure who had preserved or deteriorated systolic function, defined
      as a left ventricular ejection fraction of > 50% or < 50%, respectively, within
      two weeks of admission to hospital. METHODS: The records of 229 patients with
      congestive heart failure were studied. There were 95 women and 134 men, mean (SD)
      age 66.7 (11.7) years, who had been admitted to a cardiology department for
      congestive heart failure in the period 1991 to 1994, and whose left ventricular
      systolic function had been evaluated echocardiographically within two weeks of
      admission. Data were collected on the main clinical findings, supplementary
      investigations, treatment, and duration of hospital admission. Follow up
      information was obtained in the spring of 1998 by searching the general archives
      of the hospital and by a telephone survey. RESULTS: Left ventricular systolic
      function was preserved in 29% of the patients. The preserved and deteriorated
      groups differed significantly in the sex ratio (more women in the preserved
      group) and in the presence of a third heart sound, cardiomegaly, alveolar oedema,
      ischaemic cardiomyopathy, and treatment with angiotensin converting enzyme (ACE)
      inhibitors (all more in the deteriorated group). There were no significant
      differences in age, New York Heart Association functional class, rhythm
      disturbances, left ventricular hypertrophy, treatment with drugs other than ACE
      inhibitors, or survival. In the group as a whole, the survival rates after three
      months, one year, and five years were 92.6%, 80%, and 48.4%, respectively.
      CONCLUSIONS: In view of the unexpectedly poor prognosis of patients with
      congestive heart failure and preserved left ventricular systolic function,
      controlled clinical trials should be carried out to optimise their treatment.

PMID- 12181217
TI  - Assessment of myocardial adrenergic innervation in patients with sick sinus
      syndrome: effect of asynchronous ventricular activation from ventricular apical
      stimulation.
AB  - OBJECTIVE: To investigate ventricular sympathetic innervation in patients with
      sick sinus syndrome and to detect regional deterioration of adrenergic
      innervation caused by asynchronous ventricular activation from right ventricular
      pacing. DESIGN: Prospective controlled study. SETTING: Tertiary cardiac referral
      centre. PATIENTS: 22 patients with sick sinus syndrome and indications for
      permanent dual chamber pacing; 20 healthy individuals as controls. INTERVENTIONS:
      All patients underwent myocardial imaging with planar and single photon emission
      computed tomography (SPECT) after an intravenous infusion of 5 mCi 123I-meta
      iodobenzylguanidine (123I-MIBG) before and after pacemaker implantation. A SPECT
      thallium201 myocardial study was done during the same week as the 123I-MIBG study
      in all patients. MAIN OUTCOME MEASURES: The heart to mediastinum (H/M) ratio and
      washout rate were calculated during the 123I-MIBG study to assess the global
      cardiac sympathetic activity; the aim of the SPECT study was to investigate the
      regional distribution of adrenergic innervation. RESULTS: The H/M ratio was
      significantly smaller in the patients with sick sinus syndrome than in the
      controls (p < 0.001). In sick sinus syndrome there were regional adrenergic
      innervation defects, mostly in the inferior and apical walls. After a medium term
      pacing period, a redistribution of 123I-MIBG uptake was detected, with
      deterioration of adrenergic innervation in the inferior, apical, and posterior
      walls. The thallium201 myocardial perfusion study showed no change after three
      months of permanent pacing. CONCLUSIONS: Patients with sick sinus syndrome have
      global and regional disturbances of the adrenergic innervation of the left
      ventricular myocardium. These seem to deteriorate as a result of asynchronous
      electrical activation. The clinical significance of this finding requires further
      investigation.

PMID- 12181219
TI  - Separation of coronary ostium caused by pseudoaneurysm formation after composite
      valve graft replacement for acute dissection of the ascending aorta.

PMID- 12181218
TI  - Clinical outcomes of patients with diabetes mellitus and acute myocardial
      infarction treated with primary angioplasty or fibrinolysis.
AB  - OBJECTIVE: To compare the early and late outcomes of primary percutaneous
      transluminal coronary angioplasty (PTCA) with fibrinolytic treatment among
      diabetic patients with acute myocardial infarction (AMI). DESIGN: Retrospective
      observational study with data obtained from prospective registries. SETTING:
      Tertiary cardiovascular institution with 24 hour acute interventional facilities.
      PATIENTS: 202 consecutive diabetic patients with AMI receiving reperfusion
      treatment within six hours of symptom onset. INTERVENTIONS: Fibrinolytic
      treatment was administered to 99 patients, and 103 patients underwent primary
      PTCA. Most patients undergoing PTCA received adjunctive stenting (94.2%) and
      glycoprotein IIb/IIIa inhibition (63.1%). MAIN OUTCOME MEASURES: Death, non-fatal
      reinfarction, and target vessel revascularisation at 30 days and one year were
      assessed. RESULTS: Baseline characteristics were similar in these two treatment
      groups except that the proportion of patients with Killip class III or IV was
      considerably higher in those treated with PTCA (15.5% v 6.1%, p = 0.03) and time
      to treatment was significantly longer (103.7 v 68.0 minutes, p < 0.001). Among
      those treated with PTCA, the rates for in-hospital recurrent ischaemia (5.8% v
      17.2%, p = 0.011) and target vessel revascularisation at one year (19.4% v 36.4%,
      p = 0.007) were lower. Death or reinfarction at one year was also reduced among
      those treated with PTCA (17.5% v 31.3%, p = 0.02), with an adjusted relative risk
      of 0.29 (95% confidence interval 0.15 to 0.57) compared with fibrinolysis.
      CONCLUSION: Among diabetic patients with AMI, primary PTCA was associated with
      reduced early and late adverse events compared with fibrinolytic treatment.

PMID- 12181220
TI  - ECG determinants in adult patients with chronic right ventricular pressure
      overload caused by congenital heart disease: relation with plasma neurohormones
      and MRI parameters.
AB  - OBJECTIVE: To examine retrospectively the changes in ECG parameters over time and
      their correlation with other quantitative right ventricular (RV) function
      parameters in patients with chronic RV pressure overload caused by congenital
      heart disease. METHODS: 48 patients with chronic RV pressure overload caused by
      the following congenital heart diseases were studied: nine with congenitally
      corrected transposition of the great arteries (TGA), 12 with surgically corrected
      TGA, and 27 with a subpulmonary pressure overloaded RV. QRS duration and
      dispersion were measured manually from standard ECG recorded twice within five
      years. RV end diastolic volume (EDV) and RV mass were determined by magnetic
      resonance imaging. Brain natriuretic peptide (BNP) plasma concentrations were
      measured. RESULTS: QRS duration and QRS dispersion increased in all patient
      groups during the follow up period. QRS duration increased significantly in the
      congenitally corrected TGA (p = 0.04) and the subpulmonary pressure overloaded RV
      groups (p = 0.01). QRS dispersion increased significantly in patients with
      surgically corrected TGA (p = 0.03) and in the subpulmonary pressure overloaded
      RV group (p = 0.02). A significant correlation was found between QRS duration and
      RVEDV (r = 0.71, p < 0.0001). RV mass was significantly correlated with QRS
      duration in patients with tetralogy of Fallot (r = 0.67, p = 0.01). Mean (SD)
      plasma brain natriuretic peptide concentrations (6.6 (5.4) pmol/l) were increased
      compared with normal reference values but no correlation was found with ECG
      parameters or RV systolic pressure. No malignant arrhythmia or sudden death
      occurred. CONCLUSIONS: ECG parameters worsened gradually in asymptomatic or
      minimally symptomatic patients with chronic RV pressure overload, regardless of
      the nature of their congenital heart disease. In all patients, a significant
      positive correlation was found between QRS duration and RVEDV. In patients with
      tetralogy of Fallot there was also a correlation between QRS duration and RV
      mass.

PMID- 12181222
TI  - Displacement of the heart caused by pulmonary agenesis.

PMID- 12181221
TI  - Influence of twin-twin transfusion syndrome on fetal cardiovascular structure and
      function: prospective case-control study of 136 monochorionic twin pregnancies.
AB  - OBJECTIVE: To test the hypothesis that identical twins show no inter-twin
      differences in cardiovascular structure or physiology in fetal life unless there
      has been twin-twin transfusion syndrome. DESIGN: Unselected prospective case
      control observational study of fetoplacental haemodynamics including
      echocardiography at a median of 24 (16.7 to 32.3) weeks, with postnatal
      confirmation of congenital heart disease or normality. SETTING: Fetal medicine
      unit. PATIENTS: 136 women with monochorionic diamniotic twin pregnancies, of
      which 47 fetal twin pairs (35%) had twin-twin transfusion syndrome. RESULTS:
      There were no haemodynamic differences between the bigger fetus (twin 1) and the
      smaller co-twin (twin 2) in uncomplicated monochorionic diamniotic pairs. In twin
      twin transfusion syndrome, recipient fetuses had increased aortic and pulmonary
      velocities compared with their donor co-twins (mean (SD): 0.73 (0.23) m/s and
      0.63 (0.14) m/s), respectively, v 0.53 (0.16) m/s and 0.48 (0.10) m/s in donor
      twins; p = 0.003 (aortic) and < 0.0001 (pulmonary)), and also in comparison with
      twin 1 and twin 2. The overall prevalence of congenital heart disease was
      increased above that in singletons (3.8% v 0.56%; 6.9% in twin-twin transfusion v
      2.3% in uncomplicated monochorionic diamniotic twins), with inter-twin
      discordance for defects. The prevalence in recipient twins was 11.9% (p = 0.014 v
      uncomplicated control twins). CONCLUSIONS: Fetuses with an identical genome but
      no circulatory imbalance have similar cardiovascular physiology but discordant
      phenotypic expression of congenital heart disease. The high prevalence of
      congenital heart disease in monochorionic diamniotic twins merits detailed fetal
      echocardiography.

PMID- 12181223
TI  - Non-invasive automated assessment of the ratio of pulmonary to systemic flow in
      patients with atrial septal defects by the colour Doppler velocity profile
      integration method.
AB  - BACKGROUND: The recent introduction of the automated cardiac flow measurement
      (ACM) method, using spatiotemporal integration of the Doppler velocity profile,
      provides a quick and accurate automated calculation of cardiac output. OBJECTIVE:
      To evaluate the ACM method against oximetry during cardiac catheterisation for
      estimating the Qp/Qs (pulmonary to systemic flow) ratio in patients with an
      atrial septal defect. METHODS: Left and right ventricular stroke volume (LVSV,
      RVSV) were calculated by ACM in 22 patients with an atrial septal defect who
      underwent cardiac catheterisation and in 11 patients without heart disease
      (control group). With ACM, the Qp/Qs ratio was estimated from RVSV divided by
      LVSV. In the patients with an atrial septal defect, the Qp/Qs ratio was assessed
      by oximetry at the time of cardiac catheterisation. RESULTS: There was a good
      correlation between LVSV and RVSV obtained by ACM in the control group (r = 0.98,
      y = 0.97x + 0.25, SEE = 2.9 ml). The mean difference between LVSV and RVSV by ACM
      was -1.25 (2.76) ml. The Qp/Qs ratio obtained by ACM in the control group was
      0.98 (0.06). The Qp/Qs ratio in patients with an atrial septal defect was
      significantly higher than in the control group (3.11 (1.20), p < 0.001). ACM
      determination of the Qp/Qs ratio correlated well with oximetry determination (r =
      0.86, y = 0.75x + 0.55, SEE = 0.64). The mean difference between ACM and oximetry
      for the measurement of the Qp/Qs ratio was -0.28 (0.69). CONCLUSIONS: The newly
      developed ACM method is clinically useful for non-invasive automated estimations
      of the Qp/Qs ratio in patients with an atrial septal defect.

PMID- 12181224
TI  - New applications of intracardiac echocardiography: assessment of coronary blood
      flow by colour and pulsed Doppler imaging in dogs.
AB  - OBJECTIVE: To explore the application of a new 10 French intracardiac
      echocardiography (ICE) catheter with phased array and Doppler capable transducer
      for the assessment of epicardial and intramyocardial coronary blood flow.
      METHODS: The coronary arteries were detected by cross sectional imaging in seven
      closed chest dogs, and coronary blood flow visualised by colour Doppler. Blood
      flow velocities were recorded by pulsed Doppler at baseline for reproducibility
      of repeated measurements, and during hyperaemia for coronary flow reserve
      measurements. Comparisons were made with Doppler guide wire data obtained
      simultaneously. Intramyocardial coronary artery blood flow was assessed by colour
      flow mapping, and the blood flow velocities recorded using pulsed Doppler at
      baseline and during hyperaemia. RESULTS: Seven left main, six left anterior
      descending, seven left circumflex, and five right coronary arteries were
      visualised in the seven animals by cross sectional or colour Doppler imaging.
      Repeated measurements of coronary flow velocity showed a good correlation (mean
      diastolic velocity, r = 0.93, n = 22, p < 0.0001; peak diastolic velocity, r =
      0.96, n = 22, p < 0.0001, respectively). Intraobserver/interobserver variability
      was satisfactorily low. Coronary flow reserve from ICE correlated highly with the
      value obtained from the Doppler guide wire (r = 0.90, n = 26, p < 0.0001).
      Intramyocardial coronary blood flow was identified in all seven dogs, and flow
      velocities were recorded at baseline and during hyperaemia in four animals.
      CONCLUSIONS: This new ICE catheter provides high quality diagnostic resolution.
      It is useful for coronary blood flow assessment.

PMID- 12181225
TI  - Non-paroxysmal junctional tachycardia with type I exit block.

PMID- 12181226
TI  - A rapid and reproducible on line automated technique to determine endothelial
      function.
AB  - OBJECTIVE: To evaluate clinically a new on line, automated technique to measure
      flow mediated dilatation (FMD) as a marker of endothelial function. DESIGN:
      Prospective study. PATIENTS: 12 healthy volunteers and 12 patients with
      significant, angiographically documented coronary artery disease. INTERVENTIONS:
      Brachial arteries were imaged using a standard vascular ultrasound system with a
      5-12 MHz linear transducer. Arterial diameter was measured on line (in real time)
      by connecting the ultrasound system to a personal computer equipped with a frame
      grabber and artery wall detection software (VIA) specially developed by the
      authors' group. By using this new technique, FMD was measured following 4.5
      minutes of ischaemia of the proximal forearm in all subjects on two separate
      days. RESULTS: The mean (SD) day to day variability in FMD measurements was 0.90
      (0.48)%,which compares very favourably with current methods. The FMD measurement
      was available within seconds of completing the scan. CONCLUSIONS: Personal
      computer based automated techniques to assess FMD involve image acquisition and
      recording after which a second (off line) image interpretation session is
      required. The need for off line analysis makes current methods time consuming and
      increases the variability of measurement. This on line, automated analysis
      technique for FMD assessment reduces the variability and greatly increases the
      speed of measurement. Using this system may mean that fewer patients will be
      required in clinical trials assessing the effects of interventions on endothelial
      function. Adopting this method may also facilitate the screening of larger
      numbers of subjects for endothelial dysfunction.

PMID- 12181227
TI  - Pulmonary arteriovenous malformation and aortopulmonary collateral imaged by time
      resolved contrast enhanced magnetic resonance angiography.

PMID- 12181228
TI  - Does adenosine prevent myocardial micronecrosis following percutaneous coronary
      intervention? The ADELINE pilot trial. ADEnosine Limit myocardial Necrosis.

PMID- 12181229
TI  - Supernormal conduction mimicking a supraventricular capture beat during wide
      complex tachycardia.

PMID- 12181230
TI  - Increased circulating interleukin-18 in patients with congestive heart failure.

PMID- 12181231
TI  - Acute myocardial infarction: reperfusion treatment.

PMID- 12181232
TI  - Cardiovascular and coronary risk estimation in hypertension management.

PMID- 12181236
TI  - Back to baked potato? Or is it another "laboratory finding"?

PMID- 12181233
TI  - Off-pump coronary artery bypass surgery.

PMID- 12181237
TI  - Advanced pancreatic cancer--5 years on.

PMID- 12181238
TI  - Cyclooxygenase-2 (COX-2) a new prognostic and predictive factor for ovarian
      cancer? Are all the criteria fulfilled?

PMID- 12181239
TI  - Heating the patient: a promising approach?
AB  - There is a clear rationale for using hyperthermia in cancer treatment. Treatment
      at temperatures between 40 and 44 degrees C is cytotoxic for cells in an
      environment with a low pO(2) and low pH, conditions that are found specifically
      within tumour tissue, due to insufficient blood perfusion. Under such conditions
      radiotherapy is less effective, and systemically applied cytotoxic agents will
      reach such areas in lower concentrations than in well perfused areas. Therefore,
      the addition of hyperthermia to radiotherapy or chemotherapy will result in at
      least an additive effect. Furthermore, the effects of both radiotherapy and many
      drugs are enhanced at an increased temperature. Hyperthermia can be applied by
      several methods: local hyperthermia by external or internal energy sources,
      regional hyperthermia by perfusion of organs or limbs, or by irrigation of body
      cavities, and whole body hyperthermia. The use of hyperthermia alone has resulted
      in complete overall response rates of 13%. The clinical value of hyperthermia in
      addition to other treatment modalities has been shown in randomised trials.
      Significant improvement in clinical outcome has been demonstrated for tumours of
      the head and neck, breast, brain, bladder, cervix, rectum, lung, oesophagus,
      vulva and vagina, and also for melanoma. Additional hyperthermia resulted in
      remarkably higher (complete) response rates, accompanied by improved local tumour
      control rates, better palliative effects and/or better overall survival rates.
      Generally, when combined with radiotherapy, no increase in radiation toxicity
      could be demonstrated. Whether toxicity from chemotherapy is enhanced depends on
      sequence of the two modalities, and on which tissues are heated. Toxicity from
      hyperthermia cannot always be avoided, but is usually of limited clinical
      relevance. Recent developments include improvements in heating techniques and
      thermometry, development of hyperthermia treatment planning models, studies on
      heat shock proteins and an effect on anti-cancer immune responses, drug targeting
      to tumours, bone marrow purging, combination with drugs targeting tumour
      vasculature, and the role of hyperthermia in gene therapy. The clinical results
      achieved to date have confirmed the expectations raised by results from
      experimental studies. These findings justify using hyperthermia as part of
      standard treatment in tumour sites for which its efficacy has been proven and,
      furthermore, to initiate new studies with other tumours. Hyperthermia is
      certainly a promising approach and deserves more attention than it has received
      until now.

PMID- 12181240
TI  - A randomised trial comparing 5-FU with 5-FU plus cisplatin in advanced pancreatic
      carcinoma.
AB  - BACKGROUND: Chemotherapy is moderately efficient as a treatment for pancreatic
      adenocarcinoma, but patient survival and quality of life has improved with this
      modality in some trials. In a previous phase II trial, 5-fluorouracil (5-FU) plus
      cisplatin (FUP) yielded a 26.5% response rate and a 29% survival rate at 1 year.
      The present study aimed to compare FUP with 5-FU alone, which was the control arm
      in former Mayo Clinic trials. PATIENTS AND METHODS: Patients with untreated
      cytologically or histologically proven metastatic or locally advanced
      adenocarcinoma of the pancreas were deemed measurable or evaluable. Chemotherapy
      regimens consisted of a control FU arm (5-FU 500 mg/m(2)/day for 5 days) and the
      investigational FUP arm (continuous 5-FU 1000 mg/m(2)/day for 5 days plus
      cisplatin 100 mg/m(2) on day 1 or day 2). In both arms, chemotherapy was repeated
      at day 29. RESULTS: Two-hundred and seven patients from 18 centres were
      randomised: 103 in the FU arm and 104 in FUP arm. Treatment arms were balanced
      with respect to performance status grade 0-1 (83% versus 86%, respectively) and
      the presence of metastases (92% versus 89%, respectively). The median number of
      cycles administered was two in both arms (range 0-14). Five patients did not
      receive any chemotherapy and 45 received only one cycle. Toxicity (WHO grade 3-4)
      was lower with FU than with FUP (20% versus 48%, P <0.001), as was neutropenia
      (6% versus 23%), vomiting (4% versus 17%) and toxicity-related deaths (one versus
      four early in the trial). The response rate was low in both arms, but superior in
      the FUP arm: 12% versus 0% (intention-to-treat analysis, P <0.01). The survival
      rates at 6 months were 28% and 38% for the FU and FUP arms, respectively, and 1
      year survival rates were 9% and 17% (log-rank test, P = 0.10). One-year
      progression-free survival was 0% with FU versus 10% with FUP (log-rank test, P =
      0.0001). CONCLUSIONS: In advanced pancreatic carcinomas with a poor prognosis,
      FUP was superior to FU in terms of response and progression-free survival, but
      not in terms of overall survival. The low response rate is partly related to the
      number of patients who received only one cycle of chemotherapy. A more effective,
      better tolerated version of this FUP combination is needed.

PMID- 12181241
TI  - Optimization of 5-fluorouracil (5-FU)/cisplatin combination chemotherapy with a
      new schedule of leucovorin, 5-FU and cisplatin (LV5FU2-P regimen) in patients
      with biliary tract carcinoma.
AB  - BACKGROUND: Unresectable biliary tract carcinoma (BTC) is associated with a very
      poor prognosis. To improve efficacy and tolerance of the 5-fluorouracil (5
      FU)/cisplatin combination in BTC, we designed a new therapeutic schedule, the
      LV5FU2-P regimen. PATIENTS AND METHODS: Twenty-nine patients with advanced or
      metastatic BTC were prospectively enrolled in the study. The treatment (LV5FU2-P
      regimen) consisted of a biweekly administration of a 2-h infusion of leucovorin
      200 mg/m(2), a 400 mg/m(2) bolus of 5-FU followed by a 22-h continuous infusion
      of 600 mg/m(2) 5-FU on two consecutive days and cisplatin 50 mg/m(2) on day 2.
      Clinical symptoms, performance and weight changes were monitored. RESULTS:
      Objective responses were observed in 10 patients (34%) (95% confidence interval
      23% to 45%) including one complete response and nine partial responses
      (stabilization 38%, progression 28%). Median progression-free survival and
      overall survival were 6.5 and 9.5 months, respectively. Weight gain was observed
      in 45% of patients and performance status improved in 60%. One patient had a
      grade 4 thrombocytopenia, and grade 3 toxicity occurred in 41% of patients. There
      were no treatment-related deaths. CONCLUSIONS: This study, one of the largest
      phase II trials performed for this disease, shows that the LV5FU2-P regimen is an
      active and well-tolerated chemotherapy for advanced and metastatic BTC.

PMID- 12181242
TI  - Whole-body hyperthermia (41.8 degrees C) combined with bimonthly oxaliplatin,
      high-dose leucovorin and 5-fluorouracil 48-hour continuous infusion in pretreated
      metastatic colorectal cancer: a phase II study.
AB  - BACKGROUND: Second- and third-line treatments remain a challenge in advanced
      colorectal cancer. Studies of bimonthly regimens of high-dose leucovorin (LV) and
      5-fluorouracil (5-FU) by continuous infusion combined with oxaliplatin (L-OHP)
      have shown encouraging response rates in patients not responding to a bimonthly
      LV/5-FU regimen. Hyperthermic enhancement of L-OHP efficiency by increased DNA
      adduct formation has been demonstrated in vitro. This study was designed to
      address feasibility, toxicity and efficacy issues of whole-body hyperthermia
      (WBH) as an adjunct to L-OHP/LV/5-FU in pretreated patients after progression to
      first- and second-line treatments with LV/5-FU by continuous infusion and
      irinotecan. PATIENTS AND METHODS: Forty-four patients with advanced colorectal
      cancer, who had progressed during or within 3 months after completion of
      chemotherapy with LV/5-FU 24-h infusion (LV/5-FU(24h)) (eight patients) or
      irinotecan combined with or after LV/5-FU(24h )(36 patients), were treated with L
      OHP 85 mg/m(2), 2-h intravenous (i.v.) infusion, followed by LV 200 mg/m(2), 1-h
      i.v. infusion, and 5-FU 3 g/m(2), 48-h continuous infusion. Every second cycle of
      the biweekly regimen was combined with WBH, thus allowing a comparison of
      toxicity with and without WBH in the same patient. Whole-body hyperthermia was
      administered by a humidified radiant heat device. The target temperature of 41.8
      degrees C was maintained for 60 min. L-OHP (2-h infusion) was started at a core
      body temperature of 39 degrees C. RESULTS: All patients could be evaluated for
      toxicity, and 41 patients were evaluable for response. A total of 273 L-OHP
      containing regimens were administered, 130 with and 143 without WBH. Hyperthermic
      treatment combined with L-OHP/LV/5-FU showed no unexpected toxicities. WHO grade
      3 toxicities were rare and evenly balanced between cycles given with or without
      WBH. One early death occurred due to sepsis and tumor lysis. The overall response
      rate was 20%, with two complete and six partial responses. Twenty-three patients
      (56%) had stable disease and nine patients (22%) progressive disease. With a
      median observation time of 70 weeks, the median time to progression was 21 weeks
      [95% confidence interval (CI) 17-25 weeks] and the median survival was 50 weeks
      (95% CI 39-61 weeks) from the start of therapy. CONCLUSIONS: This trial suggests
      some advantage of combining L-OHP/LV/5-FU with WBH. Results compare favorably
      with the activity of similar regimens without WBH in less extensively pretreated
      patients. These data support further evaluation and warrant phase III studies.

PMID- 12181244
TI  - Concomitant chemoradiation versus neoadjuvant chemotherapy in locally advanced
      cervical carcinoma: results from two consecutive phase II studies.
AB  - BACKGROUND: Randomized studies comparing induction chemotherapy followed by
      surgical resection with radiation alone found that the neoadjuvant approach
      produces better results. So far, this latter modality has not been compared with
      standard concomitant chemoradiation. The objective of this report was to compare
      the results of two consecutive phase II studies: neoadjuvant chemotherapy
      followed by surgery or chemoradiation for the unresectable cases versus standard
      cisplatin-based chemoradiation. PATIENTS AND METHODS: From February 1999 to July
      1999, 41 patients with cervical carcinoma, stages IB2-IIIB, were treated with
      neoadjuvant chemotherapy. Treatment consisted of three 21-day courses of
      cisplatin 100 mg/m(2) on day 1 and gemcitabine 1000 mg/m(2) on days 1 and 8,
      followed by either surgery or concomitant chemoradiation for the non-operable
      cases. From August 1999 to December 1999, an equal number of patients having
      comparable clinicopathological characteristics were treated with six weekly
      courses of cisplatin 40 mg/m(2) during standard pelvic radiation. RESULTS: A
      total of 82 patients were analyzed. Both groups were similar with regard to age,
      histology, International Federation of Gynecology and Obstetrics (FIGO) stage,
      tumor size, pretreatment hemoglobin levels, parametrial infiltration and
      performance status. In the neoadjuvant arm the overall response rate to induction
      chemotherapy was 95% (95% confidence interval 88% to 100%). Twenty-three patients
      had surgery and 14 underwent chemoradiation. In the definitive chemoradiation
      study, 38 patients completed treatment, the median number of cisplatin courses
      was six for a dose intensity of 33 mg/m(2)/week. Doses to points A and B were 85
      Gy (range 68-95) and 55 Gy (range 51-65), respectively. Chemoradiation was
      delivered in 44.6 (range 28-113) days. Complete response rates after all
      treatment were similar: 97% and 87% in the neoadjuvant and chemoradiation groups,
      respectively. At a median follow-up of 28 (range 2-33) and 24 (range 3-30)
      months, respectively, there were no differences in overall survival. To date, 15
      and 13 patients in the neoadjuvant and chemoradiation groups, respectively, have
      died of disease (P = 0.8567). CONCLUSIONS: The results of this non-randomized
      comparison suggest that induction chemotherapy followed by surgery or
      chemoradiation is at least as effective in terms of response and survival as
      standard cisplatin-based chemoradiation. A randomized study is needed to confirm
      these findings.

PMID- 12181243
TI  - Increased cyclooxygenase-2 (COX-2) expression is associated with chemotherapy
      resistance and outcome in ovarian cancer patients.
AB  - BACKGROUND: Cyclooxygenase-2 (COX-2) expression is associated with aggressive
      clinicopathological parameters and unfavourable prognosis in several human
      malignancies. The aim of this study was to investigate the expression of COX-2
      and its association with clinicopathological parameters, response to treatment,
      and clinical outcome in ovarian cancer patients. PATIENTS AND METHODS: COX-2
      expression was analysed by immunohistochemistry in 87 primary ovarian carcinomas
      from patients with measurable disease after primary laparotomy. RESULTS: COX-2
      immunoreaction was observed in 39 (44.8%) cases, and did not differ in
      distribution according to age, FIGO stage, debulking at time of surgery, presence
      of ascites, histotype or tumour grade. Both in patients cytoreduced at first
      surgery and in those undergoing only explorative laparotomy, the percentage of
      COX-2 positivity was significantly higher in non-responding than in patients
      responding to treatment (P = 0.043 and P = 0.0018, respectively). In multivariate
      analysis, only COX-2 positivity and older age retained an independent role in
      predicting a poor chance of response to treatment. There was no significant
      difference of clinical outcome according to COX-2 status in patients undergoing
      primary debulking while, in the subgroup of patients who underwent explorative
      laparotomy, COX-2-positive cases showed a shorter time to progression (P = 0.025)
      and overall survival (P = 0.025). CONCLUSIONS: The assessment of COX-2 status
      could provide additional information in order to identify ovarian cancer patients
      with a poor chance of response to chemotherapy and potentially candidates for
      more individualised treatments.

PMID- 12181245
TI  - A randomized phase II pilot trial of adjuvant marimastat in patients with early
      stage breast cancer.
AB  - BACKGROUND: This pilot trial was performed to evaluate the safety, toxicity and
      pharmacokinetics of chronic therapy with the matrix metalloproteinase inhibitor
      marimastat in the adjuvant treatment of breast cancer. PATIENTS AND METHODS:
      Patients with high-risk node negative or node positive breast cancer received
      marimastat either 5 or 10 mg p.o. b.i.d. for 12 months. Marimastat was given
      either as a single agent following completion of adjuvant chemotherapy or
      concurrently with tamoxifen. RESULTS: Sixty-three patients were enrolled from
      June 1997 to May 1998. All patients have completed 12 months of treatment or have
      discontinued therapy due to toxicity, relapse or intercurrent illness. Moderate
      (WHO criteria) arthralgia/arthritis was reported by 34% of patients receiving 5
      mg b.i.d. and 45% of patients receiving 10 mg b.i.d.; severe arthralgia/arthritis
      was reported by 6% and 23% of patients, respectively. Six patients (19%)
      receiving 5 mg b.i.d. and 11 (35%) receiving 10 mg b.i.d. discontinued marimastat
      therapy due to toxicity. Trough plasma levels were rarely within the target range
      for biological activity (40-200 ng/ml) with mean concentration for patients
      receiving: 5 mg b.i.d. = 7.5; 5 mg b.i.d. plus tamoxifen = 6.9; 10 mg b.i.d. =
      11.9; 10 mg b.i.d. plus tamoxifen = 12.8. CONCLUSIONS: A randomized adjuvant
      trial with marimastat is not warranted as chronic administration cannot maintain
      plasma levels with the target range.

PMID- 12181246
TI  - A randomized phase II study of sequential docetaxel and
      doxorubicin/cyclophosphamide in patients with metastatic breast cancer.
AB  - BACKGROUND: Docetaxel has yielded promising response rates as a component of
      doxorubicin-based combination schedules in patients with metastatic breast
      cancer, including docetaxel/doxorubicin and
      docetaxel/doxorubicin/cyclophosphamide (AC). This randomized two-stage phase II
      study was conducted to evaluate sequential treatment with docetaxel and AC as
      first-line treatment in patients with recurrent or metastatic breast cancer
      previously untreated with chemotherapy for metastatic disease. PATIENTS AND
      METHODS: Thirty-three patients were randomized to either docetaxel (100 mg/m(2))
      on day 1 of a 21-day cycle for three cycles followed by AC (60/600 mg/m(2)) on
      day 1 of a 21-day cycle for three cycles (n = 17) or vice-versa (n = 16), without
      prophylactic granulocyte colony-stimulating factor support. In addition, we
      compared pre-treatment serum sErbB1 and sErbB2 protein concentrations with that
      of an age- and menopausal status-matched group of healthy women, and examined
      changes in serum sErbB1 and sErbB2 protein concentrations in these two treatment
      schedules. Data from each one of the two arms of the trial (docetaxel then AC, or
      AC and then docetaxel) were analyzed separately. RESULTS: Enrollment was
      suspended after the first-stage of accrual, based on statistical design.
      Confirmed objective response rates after six cycles of treatment were 35% [95%
      confidence interval (CI) 14% to 62%] with docetaxel then AC and 38% (95% CI 15%
      to 65%) with AC then docetaxel. Dose reductions were frequent and mostly due to
      grade 4 neutropenia. Median survival time was 2.5 years in the docetaxel then AC
      group, and 1.1 years in the AC then docetaxel group. Serum sErbB1 concentrations
      were not significantly different between the study patients and healthy women,
      and did not change significantly after three and six cycles of treatment. In
      contrast, serum sErbB2 concentrations were significantly higher in the study
      patients compared with healthy women and tended to decrease after three and six
      cycles of treatment. CONCLUSIONS: Response rates at the end of six cycles of
      treatment, which led to termination of accrual after the first stage using either
      the sequence of docetaxel first or docetaxel after AC chemotherapy, were lower
      than anticipated. However, median survival times and median progression-free
      survival times are similar to those reported in other studies. These data further
      suggest that additional studies to assess whether serum sErbB2 concentrations are
      useful predictors of responsiveness to chemotherapy are warranted.

PMID- 12181247
TI  - Management of women with ductal carcinoma in situ of the breast: a population
      based study.
AB  - BACKGROUND: Increasing incidence of ductal carcinoma in situ (DCIS) confronts
      patients and clinicians with optimal treatment decisions. This multidisciplinary
      study investigates therapeutic modalities of DCIS in daily practice and provides
      recommendations on how to increase quality of care. PATIENTS AND METHODS: All
      women (n = 116) with unilateral DCIS recorded in the Geneva Cancer Registry from
      1995 to 1999 were considered. Information concerned patient and tumor
      characteristics, treatment and outcome. Factors linked to therapy were determined
      using a case-control approach. Cases were women with treatment of interest and
      controls other women on the study. RESULTS: Most DCIS cases (62%) were discovered
      by mammography screening. Ninety (78%) women had breast-conserving surgery (BCS),
      18 (16%) mastectomy and seven (6%) bilateral mastectomy. Eight (7%) patients had
      tumor-positive margins, 18 (16%) lymph node dissection and two (1.7%)
      chemotherapy. Twenty-five per cent of women with BCS had no radiotherapy, three
      had radiotherapy after mastectomy. Less than 50% underwent breast reconstruction
      after mastectomy. Method of discovery, multifocality, tumor localization, size
      and differentiation were linked to the use of BCS or lymph node dissection.
      CONCLUSIONS: Because of important disparities in DCIS management, recommendations
      are made to increase quality of care, in particular to prevent axillary
      dissection or bilateral mastectomy and to increase the use of radiotherapy after
      BCS.

PMID- 12181248
TI  - Loss of cyclin D1 and p16 expression correlates with local recurrence in
      nasopharyngeal carcinoma following radiotherapy.
AB  - BACKGROUND: The cyclin D1/p16/Rb pathway plays a critical role in tumorigenesis
      and each component of this pathway may be affected in various malignancies. The
      purpose of this study was to investigate the expression and prognostic
      significance of these proteins in nasopharyngeal carcinoma (NPC). PATIENTS AND
      METHODS: Sixty-five patients undergoing radiotherapy for NPC were analyzed. The
      expression of cyclin D1, p16 and pRb was evaluated with immunohistochemical
      analysis of archived pretreatment tumor materials and expression of these
      proteins was correlated with clinicopathological parameters. RESULTS: Positive
      expression of cyclin D1 was observed in 43 of 65 NPCs (66%). p16 and pRb
      inactivation was identified in 42 of 65 (65%) and four of 65 (6%) tumors,
      respectively. All but seven tumors (58 of 65, 89%) contained at least one
      alternation in the cyclin D1/p16/Rb pathway. Loss of cyclin D1 as well as p16 was
      closely related to local recurrence after radiotherapy for NPC (P = 0.015 and
      0.047). No association between pRb expression and clinicopathological outcome was
      apparent. CONCLUSIONS: The study's results suggest that the cyclin D1/p16/Rb
      pathway plays an important role in NPC tumorigenesis. We also find that cyclin D1
      and p16 protein levels in NPC may be of use clinically as a predictor of local
      tumor control.

PMID- 12181249
TI  - Combination gemcitabine and cisplatin chemotherapy for metastatic or recurrent
      nasopharyngeal carcinoma: report of a phase II study.
AB  - BACKGROUND: To evaluate the efficacy and toxicity of combination gemcitabine plus
      cisplatin (GC) chemotherapy in metastatic or recurrent nasopharyngeal carcinoma
      (NPC). PATIENTS AND METHODS: Forty-four patients of Chinese ethnicity with
      metastatic or recurrent NPC received ambulatory GC chemotherapy every 28 days
      (gemcitabine 1000 mg/m(2) days 1, 8 and 15; cisplatin 50 mg/m(2) days 1 and 8).
      There were 40 male and four female patients with a mean age of 47.4 years. More
      than half (54.5%) of the patients had received either prior platinum-based
      chemotherapy and/or radiotherapy to target lesions. RESULTS: There were nine
      complete responses and 23 partial responses in the 44 patients, achieving an
      overall response rate of 73% (78% for the 41 assessable patients). The mean
      duration of response was 5.3 months. Improved subjective symptom-control scores
      were found in 78% of patients with pre-existing symptoms, while 64% of patients
      experienced improved general well-being scores. Toxicity was mainly
      hematological: grade III/IV anemia, granulocytopenia and thrombocytopenia were
      found in 11, 37 and 16% of cycles, respectively. With a median follow-up of 17.2
      months, 62% survived 1 year while 36% were alive and progression free.
      CONCLUSIONS: Gemcitabine plus cisplatin chemotherapy offers a satisfactory
      overall response rate, subjective patient improvement and safety profile for
      metastatic and recurrent NPC.

PMID- 12181250
TI  - Neovastat (AE-941) in refractory renal cell carcinoma patients: report of a phase
      II trial with two dose levels.
AB  - BACKGROUND: renal cell carcinoma (RCC) is a potential target for anti-angiogenic
      drugs because of its high vascularization. Neovastat (AE-941) is an inhibitor of
      angiogenesis with a mechanism of action that could prove beneficial in the
      treatment of RCC. Patients and design A phase II trial was conducted to identify
      the long-term safety profile of Neovastat in advanced cancer patients and to
      obtain preliminary information on its efficacy in solid tumors refractory to
      standard treatments. Neovastat (60 or 240 ml/day) was administered orally
      (b.i.d.) to 144 patients with solid tumors refractory to standard therapies or
      for whom no standard treatments were available. RESULTS: A survival analysis was
      conducted on 22 patients with a primary diagnosis of refractory RCC to determine
      whether the dose of Neovastat had any effect. A significant relationship between
      dose and survival was observed; the median survival time was significantly longer
      (16.3 versus 7.1 months; P = 0.01) in patients treated with Neovastat 240 ml/day
      (n = 14) compared with patients receiving 60 ml/day (n = 8). No dose-limiting
      toxicity was reported. The most frequent adverse event was taste alteration
      (13.6%). CONCLUSIONS: Neovastat is well tolerated by advanced cancer patients at
      doses of 60 and 240 ml/day. The higher dose of Neovastat administered in this
      trial is associated with a survival benefit in RCC, which is not explained by
      differences in major prognostic factors.

PMID- 12181251
TI  - An international evaluation of CODOX-M and CODOX-M alternating with IVAC in adult
      Burkitt's lymphoma: results of United Kingdom Lymphoma Group LY06 study.
AB  - BACKGROUND: Burkitt's lymphoma (BL) is a rare and rapidly progressive form of B
      cell non-Hodgkin's lymphoma. Cyclophosphamide, vincristine, doxorubicin, high
      dose methotrexate (CODOX-M)/ifosfamide, etoposide and high-dose cytarabine (IVAC)
      is a highly effective alternating non-cross-resistant regimen developed by
      Magrath et al. (Magrath I., Adde M., Shad A. et al. J Clin Oncol 1996; 14: 925
      934) at the US National Cancer Institute. The aim was to confirm these results in
      a larger, international, multi-centre study using International Prognostic Index
      based criteria to assign prognostic groups, whilst slightly simplifying the
      protocol. PATIENTS AND METHODS: A phase II study where: (i) low risk (LR)
      patients were treated with three cycles of modified CODOX-M; and (ii) high risk
      (HR) patients received treatment with four cycles of alternating modified CODOX-M
      and IVAC chemotherapy. Target of 60 patients, fit for protocol treatment, from 16
      to 60 years of age with locally diagnosed, non-HIV-related, non-organ-transplant
      related BL. RESULTS: Results are given for 52 of 72 registered patients whose
      pathological eligibility was confirmed by central pathology review: 12 LR plus 40
      HR. The majority of patients (n = 41) completed protocol treatment, but toxicity
      was severe, especially myelosuppression and mucositis. Overall, 2-year event-free
      survival (EFS) was 64.6% (95% CI 50.4% to 78.9%) and 2-year overall survival (OS)
      was 72.8% (95% CI 59.4% to 86.3%). For LR, 2-year EFS was 83.3% and OS was 81.5%.
      For HR, 2-year EFS was 59.5% and OS was 69.9%. CONCLUSIONS: This study confirms
      high cure rates with this CODOX-M/IVAC approach.

PMID- 12181252
TI  - Age-related differences among patients with follicular lymphoma and the
      importance of prognostic scoring systems: analysis from a population-based non
      Hodgkin's lymphoma registry.
AB  - BACKGROUND: The influence of age on the outcome of follicular non-Hodgkin's
      lymphoma (FL) was studied in a population-based non-Hodgkin's lymphoma registry.
      PATIENTS AND METHODS: This study comprised 214 follicular lymphoma patients.
      Grade I/II was considered separately from grade III FL. The data were analyzed
      with respect to three age groups: <60, 60-69 and >or=70 years. RESULTS: The
      overall survival rate decreased in the older age groups. Grade III patients
      showed a statistically significant decrease in overall survival in comparison
      with grade I/II patients (P = 0.03). Cause-specific survival analysis showed that
      in the older age groups, there was an increasing influence of concomitant disease
      on the death rate, especially among grade III FL patients >70 years of age. The
      survival curve in grade III FL patients was shown to reach a plateau. The
      prognostic scoring system, according to the Italian Lymphoma Intergroup, fitted
      better to grade I/II patients, while the International Prognostic Index showed
      better discrimination amongst grade III patients. CONCLUSIONS: Separate grading
      for follicular lymphoma is useful. An age >70 years has a negative impact on
      outcome, but the contribution of concomitant disease herein is important.
      Different prognostic scoring systems should be applied to the different grades of
      FL.

PMID- 12181253
TI  - Bendamustine is effective in relapsed or refractory aggressive non-Hodgkin's
      lymphoma.
AB  - BACKGROUND: Bendamustine, an alkylating agent with a nitrogen mustard group and a
      purine-like benzimidazol group, has been shown to be effective in several solid
      tumors and indolent non-Hodgkin's lymphomas, but has not yet been studied for
      efficacy in aggressive lymphomas. PATIENTS AND METHODS: We conducted a phase II
      study in patients with relapsed or refractory high-grade non-Hodgkin's lymphomas,
      using bendamustine at a dose of 120 mg/m(2) on days 1 and 2, every 3 weeks for up
      to six cycles. Twenty-one patients were enrolled; 18 were evaluable for response
      and toxicity, 10 of whom were refractory to previous chemotherapy. RESULTS: With
      three patients achieving a complete response (at 6, >or=8 and >or=22 months) and
      five a partial response (three at 2 months, one at 3 months and one at 10
      months), the total response rate of the evaluable patients was 44% (eight out of
      18; 38% of all patients). Two complete and two partial responders were refractory
      to prior treatment. In 10 patients, treatment had to be stopped after one to
      three cycles due to progressive disease or hematological toxicity (n = 2). Non
      hematological side effects were mild. Eight (13%) WHO grade 3 and no grade 4
      events were observed in 60 evaluable treatment cycles. Hematologic toxicity was
      moderate (grade 3 and 4): anemia in five cycles (8%), leukopenia in seven (12%)
      and thrombocytopenia in eight (13%). CONCLUSIONS: Bendamustine as a single agent
      is effective against aggressive lymphoma, even in cases of refractory disease.
      Further studies are warranted to determine the significance of bendamustine in
      the treatment of aggressive lymphomas.

PMID- 12181254
TI  - Primary cutaneous non-Hodgkin's lymphoma with aggressive histology: inferior
      outcome is associated with peripheral T-cell type and elevated lactate
      dehydrogenase, but not extent of cutaneous involvement.
AB  - BACKGROUND: The aim of this study was to explore the association between extent
      of cutaneous involvement, presenting features and progression-free survival (PFS)
      in patients with primary cutaneous non-Hodgkin's lymphoma (PCNHL) of aggressive
      histology. METHODS: Previously untreated patients with localized or extensive
      PCNHL of aggressive histology, treated with combination chemotherapy, but
      excluding lymphoblastic lymphoma and mycosis fungoides and its variants, were
      reviewed retrospectively. RESULTS: We identified 53 patients, of whom 52 (35
      males, 17 females) were treated with doxorubicin-based regimens. Median age was
      52 years (range 25-81 years), and disease was localized and extensive in 37 and
      16 patients, respectively. Twenty-four patients had diffuse large B-cell
      lymphoma, nine had grade 3 follicular lymphoma, 13 had peripheral T-cell lymphoma
      (PTCL; not otherwise specified) and seven had anaplastic large cell lymphoma (WHO
      classification). With a median follow-up of 101 months (range 2-237 months) for
      survivors, the 10-year PFS was 65 +/- 7% and overall survival was 72 +/- 8%. The
      first failure involved the skin in 33% of B-cell and 91% of relapsing T-cell
      lymphomas. Univariate analysis revealed that PTCL (P = 0.005), lymphopenia (P =
      0.01) and high serum levels of beta(2)-microglobulin (P = 0.0006) and LDH (P =
      0.002), but not extent of skin involvement, were associated with inferior PFS.
      Multivariate analysis revealed that only PTCL and high serum lactate
      dehydrogenase (LDH) were independently associated with inferior PFS. CONCLUSIONS:
      PTCL and elevated serum LDH level, but not extent of cutaneous involvement are
      associated with inferior PFS in aggressive PCNHL treated with combination
      chemotherapy.

PMID- 12181255
TI  - Relationship between objective responses in phase I trials and potential efficacy
      of non-specific cytotoxic investigational new drugs.
AB  - BACKGROUND: Although the evaluation of new investigational drugs in phase I, II
      and III trials requires considerable time and patient resources, only a few of
      these drugs are ultimately established as anticancer drugs. MATERIALS AND
      METHODS: We collected papers of phase I trials by a Medline search using the key
      words 'Neoplasms/Drug Therapy in MeSH' and 'Phase I' for the period from 1976 to
      1993. A drug was defined as 'effective' if a regimen including the drug produced
      positive results in at least one phase III trial. We analyzed the relationship
      between objective (complete and partial) responses in phase I trials and the
      effectiveness of agents in phase III trials. RESULTS: A total of 399 single-agent
      phase I trials of cytotoxic agents in adult patients with solid tumors were
      obtained. Further clinical investigation was not recommended in 36 trials (9%)
      because of severe toxicity. In the remaining 363 trials, 174 drugs were evaluated
      and the median number of trials for each drug was two (range one to nine).
      Objective responses were observed in 495 (4.1%) of 12 076 patients, 178 (49%) of
      363 trials, and 115 (66%) of 174 drugs. Of the 174 drugs, 48 (28%) were
      considered to be effective. Percentages of effective drugs rose as the number of
      responders in phase I trials increased. Logistic regression analyses showed the
      number of responders to be significantly associated with drug effectiveness [odds
      ratio = 1.16 (1.06-1.27), P = 0.001 for 174 drugs; odds ratio = 1.16 (1.05-1.28),
      P = 0.0038 for 363 trials]. Although 10 active drugs failed to produce an
      objective response in phase I trials, seven of them produced a tumor regression
      of <50%, and three reportedly produced objective responses in phase I trials
      conducted before 1975. The numbers of responders among patients with lung,
      ovarian, breast or colorectal cancer, but not those among patients with lymphoma,
      melanoma, sarcoma or renal-cell carcinoma, were associated significantly with
      drug effectiveness against the respective tumors. CONCLUSIONS: Objective
      responses observed in phase I trials are important for determining the future
      development of an anticancer drug.

PMID- 12181256
TI  - Assessment of the risk/benefit ratio of phase II cancer clinical trials by
      Institutional Review Board (IRB) members.
AB  - BACKGROUND: This study examined the assessment of risk/benefit ratios for phase
      II cancer clinical trials by Institutional Review Board (IRB) members. PATIENTS
      AND METHODS: Semi-structured interviews were conducted with 53 IRB members from
      six research hospitals and specialized cancer centers in The Netherlands.
      RESULTS: While the toxicity and side-effects of treatment were most often
      identified as risks associated with participating in a phase II trial,
      approximately two-thirds of IRB members also cited psychosocial and/or quality-of
      life risks. Conversely, 68% of the respondents identified psychosocial benefits
      of trial participation, while 25% cited treatment effectiveness as a possible
      benefit. Between one-quarter and two-thirds of respondents indicated that trial
      protocols provide insufficient information regarding the likelihood, magnitude
      and duration of both risks and benefits. Between 15% and 34% of IRB members
      reported feeling less than fully competent at evaluating various aspects of phase
      II protocols (e.g. originality and feasibility of the study, adequacy of the
      methods and analysis procedures, etc.). This was particularly the case for non
      physician IRB members. Few IRB members reported weighing risks and benefits in a
      systematic manner, but rather relied on global impressions or preferred to leave
      such matters to the IRB as a whole or to their patients. CONCLUSIONS: A
      substantial minority of IRB members believes that trial protocols provide too
      little information relevant to evaluating various cost/benefit and scientific
      issues, and feels less than fully competent in carrying out such evaluations. IRB
      members are more likely to identify psychosocial benefits than physical health
      benefits that may accrue to patients participating in phase II trials.

PMID- 12181257
TI  - Exacerbation of oxaliplatin neurosensory toxicity following surgery.
AB  - Combination of chemotherapy and surgical resection of metastases is the most
      promising strategy to improve the fraction of long-term survivors and cured
      patients in metastatic colorectal cancer. We reproducibly observed evidence of
      exacerbation of the oxaliplatin-induced neurosensory toxicity following surgery.
      Total, protein-bound and intra-erythrocytic concentrations of oxaliplatin were
      measured, whenever possible, immediately prior to surgery and 4, 24 and 48 h
      following surgical resection. Among 12 patients, seven (58%) patients reported
      immediate post-operative aggravation of the pre-existing neurotoxicity. At the
      time of surgery, we detected high intra-erythrocytic platinum concentrations in
      all patients (median: 1365 micro g/l, range: 820-2968 micro g/l). While
      ultrafilterable oxaliplatin was not detectable prior to surgery, it could be
      detected immediately after surgery and during 48 h. These results suggest that
      patients heavily pretreated with oxaliplatin may experience aggravation of
      neurotoxicity after surgery, probably through a redistribution of the pool of
      intra-erythrocytic oxaliplatin biotransformation products into the plasma. This
      clinical observation might be the consequence of peroperative hemolysis.

PMID- 12181258
TI  - Adjuvant interferon for melanoma.

PMID- 12181259
TI  - Planning palliative or terminal care: the dilemma of doctors' prognoses in
      terminally ill cancer patients.

PMID- 12181262
TI  - Proliferation in African breast cancer: biology and prognostication in nigerian
      breast cancer material.
AB  - Three hundred cases of invasive breast carcinoma from the University of Calabar
      Teaching Hospital, Nigeria were subjected to evaluation of proliferative activity
      by mitotic counts. The prognostic significance and association with other
      prognostic factors were evaluated. The mitotic activity was expressed as mitotic
      activity index (MAI), and standardized mitotic index (SMI). Pearson's correlation
      and univariate and multivariate Cox's regression were used. The mean follow-up
      time was 25.9 months. The mean values of SMI and MAI were 42.6 mitotic figures
      per square millimeter and 30.5 mitotic figures per 10 high-power fields,
      respectively, and these were much higher than values reported for Europe or other
      Western countries. The SMI had a positive correlation with tumor size (r = 0.31,
      P <.0001), histologic grade (r = 0.68, P <.0001), nuclear area (r = 0.45, P
      <.0001), and negative correlation with fraction of fields with tubular
      differentiation (FTD; r = -0.56, P = <0.0001). There was no statistically
      significant difference in the mitotic activity between the postmenopausal and the
      premenopausal patients. Also, lymph node-positive patients had higher counts than
      did lymph node-negative patients. Earlier determined grading associated decision
      thresholds divided the patients into groups of favorable and unfavorable
      prognosis. However, the statistically optimal thresholds for Nigerian material
      were different (32 and 92 mitotic figures per square millimeter for SMI). Tumor
      size of 5 cm, SMI, and MAI were independent prognostic factors. Nigerian breast
      cancers are high-grade, high-stage, and high-proliferating cancers occurring in a
      younger population than those of the Western countries. Proliferation is also
      more active. Evaluation of SMI or MAI can improve the distinction between
      aggressive and less aggressive variants of breast cancer.

PMID- 12181263
TI  - Upper tract urothelial carcinoma: a clinicopathologic study including
      microsatellite instability analysis.
AB  - Urothelial carcinoma of the renal pelvis and ureter may develop as a
      manifestation of the hereditary nonpolyposis colorectal cancer syndrome that is
      characterized by mutations in a number of DNA mismatch repair genes and
      detectable as microsatellite instability. In this study, we examined
      microsatellite instability and the clinicopathologic features of urothelial
      carcinoma of the renal pelvis (n = 61) and ureter (n = 53) from 114 consecutive
      patients surgically treated from 1985-1992. Clinical data were obtained through
      chart review. Matched normal and tumor DNA was extracted from paraffin-embedded
      tissue, and a panel of six microsatellite loci was analyzed. The male-female
      ratio was 2.8:1 with a median age of 70 years (range, 28 to 92 y). Microsatellite
      analysis was successful in 67 tumors, and 21 (31.3%) patients had tumors that
      exhibited microsatellite instability. Patients with microsatellite-unstable
      tumors were significantly more likely to have additional nonurologic cancers (P
      =.015) including colorectal carcinoma (P =.001) compared with patients with
      tumors that did not exhibit microsatellite instability. In addition, patients
      with microsatellite-unstable tumors showed more colorectal cancers in their
      family (P =.026) and were more likely to have higher grade urothelial carcinoma
      of the upper tract (P =.028). Grade and stage, but not microsatellite status,
      were the strongest predictors of cancer-specific survival. This study found the
      highest frequency of microsatellite instability in upper urothelial tract
      carcinomas reported to date and highlights upper tract urothelial carcinoma as a
      marker of the hereditary nonpolyposis colorectal cancer syndrome in some
      patients. These findings reinforce the importance of obtaining cancer histories
      in patients with upper tract urothelial carcinoma to subsequently identify
      individuals with the hereditary nonpolyposis colorectal cancer syndrome and at
      risk relatives for surveillance and management programs.

PMID- 12181264
TI  - Analysis of histological and immunohistochemical patterns of the liver in
      posthepatitic and alcoholic cirrhosis by computerized morphometry.
AB  - To assess the degree of fibrosis and the structural changes affecting parenchymal
      and extraparenchymal components in liver cirrhosis, a computerized morphometric
      model has been applied to liver specimens from patients with posthepatitic and
      alcoholic cirrhosis. All specimens have been stained with chromotrope-aniline
      blue method and monoclonal antibodies against cytokeratin 7, CD31, and VIII
      factor. Volume fractions of parenchymal compartment and fibrosis have been
      determined stereologically on CAB slices; moreover, volume fractions of portal
      bile ducts and proliferated bile ductules, hepatocytes with biliary metaplasia,
      capillary units, and vascular structures have been measured. Volume fraction of
      fibrosis was higher in alcoholic cirrhosis when compared with the case of
      posthepatitic cirrhosis. Volume fractions describing parenchymal compartment
      showed a similar trend in both viral groups. The main differences were related to
      immunohistochemical stainings. Volume fraction of hepatocytes with biliary
      metaplasia was higher in hepatitis C virus-related cirrhosis, whereas volume
      fractions of biliary structures were more prominent in hepatitis B virus-related
      cirrhosis. Capillary units were more prominent in posthepatitic cirrhosis than in
      alcoholic cirrhosis. Interestingly, both forms of posthepatitic cirrhosis show
      similar features when compared with alcoholic cirrhosis. Our computerized
      morphometric model well describes and quantifies the morphological alterations of
      the liver, and it could represent an adjunctive tool to evaluate the degree of
      dysplastic phenomena involving parenchymal and extraparenchymal components.

PMID- 12181265
TI  - Chromosomal imbalances in diffuse large B-cell lymphoma detected by comparative
      genomic hybridization.
AB  - Diffuse large B-cell lymphoma (DLBCL) is the most common form of non-Hodgkin
      lymphoma. In contrast to many other hematological malignancies, no chromosomal
      abnormalities with a diagnostic or prognostic value have been identified in
      DLBCL. Numerical chromosomal imbalances were characterized by comparative genomic
      hybridization (CGH) performed on 54 DLBCL tumors from a total of 40 patients. The
      clonal relatedness was demonstrated in 9 of 11 pairs of matched diagnostic tumors
      and their relapses as determined by IGH gene rearrangement analysis and/or the
      CGH profiles. Furthermore, immunohistochemical expression analyses of BCL2 and
      BCL6/LAZ3 were performed on all cases. Copy number changes were detected in 94%
      of the diagnostic tumor samples and in all of the relapses. Chromosomal losses in
      diagnostic tumors were preferentially observed at 8p22-pter (29%), 1p34-pter
      (26%), 6q23-qter (20%), 17p12-pter (17%) and 22q (17%), 9p23-pter (14%), whereas
      gains were mainly seen in Xq25-26 (43%), 13q22 (26%), 12cen-q14 (20%), 3q24-25
      (11%), 7 (11%), and 18q12-21 (11%). Loss of 22q was significantly more commonly
      seen in the diagnostic tumor samples with more advanced clinical stage in other
      words, Stage III-IV compared with Stage I-II, and band 18q21 was significantly
      more often gained in relapses as compared to diagnostic tumors. None of the
      recurrent alterations were detected as a single abnormality, suggesting that
      other genetic lesions below the detection level of CGH may be the initiating
      event in the tumorigenesis of DLBCL. However, the distribution of CGH alterations
      support the idea of a progression of genetic events where loss of 8p and 9p and
      gain of 3q, 13q, and 18q would represent relatively early events because they
      were distributed in tumors with only two abnormalities.

PMID- 12181266
TI  - The potential value of comparative genomic hybridization analysis in effusion-and
      fine needle aspiration cytology.
AB  - Comparative genomic hybridization (CGH) is a molecular cytogenetic technique that
      provides an overview on chromosomal imbalances within the whole tumor cell
      genome. This method has yet not been applied in effusion cytology. We performed
      CGH analysis in malignant effusions, fine needle aspirates, and imprint smears
      from eight ovarian adenocarcinomas, three breast carcinomas, one colon
      adenocarcinoma, and three malignant mesotheliomas. In part, CGH analysis from
      fresh frozen tissue and classic karyotyping served as controls. In this series,
      14/15 cytologic specimens were suitable for extraction of high molecular weight
      DNA sufficient for reliable CGH analysis. CGH profiles from cytologic material
      were equal or even more significant in comparison with corresponding fresh frozen
      tumor samples. We conclude that CGH analysis from cytologic specimens may support
      the primary cytologic diagnosis of malignancy, especially in the differential
      diagnosis of benign proliferating mesothelium, malignant mesothelioma, and
      metastatic adenocarcinoma. CGH analysis of metastatic lesions may provide
      information on the site of the primary tumors and detects cytogenetic imbalances
      affecting oncogenes and tumor suppressor genes involved in tumor progression and
      metastatic spread.

PMID- 12181268
TI  - Prognostic value of intratumoral neutrophils in advanced gastric carcinoma in a
      high-risk area in northern Italy.
AB  - Several lines of evidence indicate that neutrophils act nonspecifically against
      tumor cells. The correlation between tumor-infiltrating neutrophils (TINs) and
      clinicopathological features remains unclear and deserves to be investigated. To
      analyze the prognostic influence of TINs in gastric carcinoma, the authors
      selected 273 patients with advanced gastric carcinoma who underwent gastrectomy
      at Cremona Hospital (Lombardia, Italy) between 1990 and 1995 and followed them
      for a period of 5 years. The number of TINs was assessed in a semiquantitative
      manner using the mean value of 20 nonoverlapping high-power fields
      (magnification, 400x; 0.08 mm(2)). The patients were divided into two groups:
      patients with a moderate or extensive amount of TINs (n = 76; >10 TINs per 20
      high-power fields) and patients with a minor amount of TINs (n = 197; <or=10 TINs
      per 20 high-power fields). The Kaplan-Meier method and Greenwood formula were
      used to estimate the crude survival rates in the two groups. Multivariate
      analyses based on the Cox proportional hazard regression model were performed to
      assess the effect of the prognostic factors on survival. Among the potential
      prognostic factors analyzed by univariate analysis, sex, age, location of
      neoplasia, pTNM stage, TINs, and surgical curability were significantly
      associated with higher survival rate. The study of the possible interaction
      effects of the clinical-pathological factors with TINs reveals that female
      patients with a moderate or extensive amount of TINs have about a 39% reduction
      in their risk of mortality, whereas male patients do not seem to be affected by
      the level of TINs. These results suggest that women appear to have a better
      prognosis than men in advanced gastric carcinoma. Gender differences in some host
      defense mechanisms and particularly in neutrophil function may be responsible for
      this event. Confirmation of these findings would give valuable insights about
      host reaction to gastric cancer growth and, ultimately, possibly would have
      implications regarding the identification of low-risk patients who could be
      spared adjuvant therapy.

PMID- 12181267
TI  - Hepatocellular carcinomas show abnormal expression of fibronectin protein.
AB  - Fibronectin plays an important role in cell-to-cell adhesion, cell migration, and
      cell signaling. In the liver, fibronectin expression has been studied primarily
      as a component of the extracellular matrix, but little information is available
      on the expression of fibronectin protein in the neoplastic cells of
      hepatocellular carcinomas (HCCs). Twenty-four surgically resected HCCs were
      immunostained with fibronectin. Tumor and normal liver tissues were concurrently
      analyzed in all cases, and expression in the tumor was evaluated in comparison to
      the nonneoplastic liver. The average age at resection was 54 +/- 18 years for the
      18 men and 6 women. Twenty-one of the cases were classic HCCs including 6 cases
      that were well differentiated, 12 cases moderately differentiated, and 3 cases
      poorly differentiated. The remaining 3 cases were moderately differentiated
      fibrolamellar carcinomas. In the normal liver, fibronectin labeled the sinusoids
      and weakly to moderately stained the cytoplasm of hepatocytes. In HCCs, 15/24
      showed overexpression of fibronectin in the cytoplasm, 8/24 showed no change from
      the nonneoplastic liver, and one case showed decreased cytoplasmic staining. In
      addition, an abnormal membranous staining pattern was noted in 16/24 HCCs. In
      contrast to the HCCs, none of the three fibrolamellar carcinomas showed increased
      cytoplasmic or membranous staining. Excluding fibrolamellar carcinoma, increased
      cytoplasmic staining and/or an abnormal membranous staining was noted in 19/21
      (90%) of HCCs. Fibronectin shows abnormal cytoplasmic and/or membranous staining
      in the majority of HCCs. The implications of fibronectin overexpression are
      uncertain but may reflect a critical step in tumor genesis.

PMID- 12181269
TI  - Differential expression of thymus and activation regulated chemokine and its
      receptor CCR4 in nodal and cutaneous anaplastic large-cell lymphomas and
      Hodgkin's disease.
AB  - Recent studies demonstrated that Hodgkin/Reed-Sternberg (H/RS) cells in Hodgkin's
      disease (HD) express thymus and activation-regulated chemokine (TARC), whereas
      reactive lymphocytes surrounding H/RS cells express its ligand, CC-chemokine
      receptor 4 (CCR4). Because in vitro studies showed that CCR4 expression is a
      marker for lymphocytes bearing a T-helper 2 (Th2) phenotype, it was suggested
      that expression of TARC is a new immune escape mechanism in HD. To find out
      whether this mechanism might also be operative in CD30+ malignant lymphomas other
      than HD, TARC and CCR4 expression was investigated by immunohistochemistry on
      paraffin and frozen-tissue sections of 39 nodal CD30+ anaplastic large cell
      lymphomas (ALCL), including 27 ALK-negative and 12 ALK-positive ALCL, 25 primary
      cutaneous CD30+ ALCL, including 11 patients with lymphomatoid papulosis, and 31
      cases of HD. TARC was expressed by the neoplastic cells in 12/27 (44%) nodal ALK
      negative ALCL and all cases of classic HD, but not in nodal ALK-positive ALCL
      (0/12) and only rarely in primary cutaneous CD30+ ALCL (3/25). In contrast, CCR4
      was expressed by the neoplastic cells in 9/9 cutaneous CD30+ ALCL, and in 9/15
      (60%) nodal ALK-negative ALCL, but only in 1/4 (25%) nodal ALK-positive ALCL and
      not by the H/RS cells in HD (0/8). Apart from three cases of HD showing 10 to 15%
      CCR4-positive lymphocytes surrounding TARC-positive H/RS cells, CCR4-positive
      reactive T cells were few (<5%) in all other cases studied. Our results
      demonstrate a differential expression of TARC and CCR4 in different types of
      CD30+ malignant lymphomas. The small number of CCR4-positive reactive T cells in
      most cases studied argues against an important role of TARC expression in the
      evasion of antitumor responses.

PMID- 12181270
TI  - Chronic sclerosing sialadenitis of the submandibular gland is mainly due to a T
      lymphocyte immune reaction.
AB  - The aim of our study was to investigate the role of immunopathological processes
      in the pathogenesis of chronic sclerosing sialadenitis of submandibular glands
      (Kuttner tumor). For this purpose, biopsy specimens from submandibular glands of
      22 patients with the histological diagnosis of chronic sclerosing sialadenitis
      were analyzed. Paraffin-embedded tissues were immunostained for T-lymphocyte
      subsets (CD3, CD4, CD8), cytotoxic T cells (granzyme B), B cells (CD20, Ki-B3),
      and macrophages (Ki-M1P). Polymerase chain reaction and capillary electrophoresis
      were used to detect rearrangements of the T-cell receptor gamma chain and the
      CDRIII region of the immunoglobulin heavy chain. In all cases, abundant cytotoxic
      T cells were found, especially in close association with ducts and acini. T-cell
      receptor gamma chain rearrangements showed a monoclonal pattern in 6 cases
      (27.3%), an oligoclonal pattern in 8 (36.4%), and a polyclonal pattern in 8
      (36.4%). The B-cell reaction was less pronounced and largely restricted to lymph
      follicles. Molecular analysis of immunoglobulin heavy chain revealed a polyclonal
      rearrangement in 17 cases (77.3%). In conclusion, there is an intimate
      relationship between the T-cell-dominated inflammatory infiltrate and acinar and
      duct cells. This, together with the frequent demonstration of monoclonal and
      oligoclonal populations of cytotoxic T cells and their histopathological
      behavior, suggests that chronic sclerosing sialadenitis may be the result of an
      immune process triggered by intraductal agents.

PMID- 12181271
TI  - Male breast carcinoma: correlation of ER, PR, Ki-67, Her2-Neu, and p53 with
      treatment and survival, a study of 65 cases.
AB  - Male breast cancer is rare, and experience of it in any single institution is
      limited. Our current understanding regarding its biology, natural history, and
      treatment strategies has been extrapolated from its female counterpart. The aim
      of this study is to evaluate the expression patterns of estrogen receptor (ER),
      progesterone receptor (PR), MiB1 (Ki67), Her-2/neu (c-erbB2), and p53 and to
      correlate them with the prognosis, presentation, staging, management, and
      survival/outcome in male breast carcinoma identified through the Veterans
      Administration nationwide cancer registry. Sixty-five cases of male breast cancer
      were reviewed for classification. Tumor blocks were requested from each
      institution for immunohistochemical staining and evaluation of ER, PR, p53, Her2
      neu, and MiB1. Seventeen age- and disease-matched male veteran patients with
      breast gynecomastia were used as controls. Traditional prognostic data were
      collected for comparison with female breast cancers (i.e., age, lymph node
      status, clinical staging, tumor size, histological grade, and disease-free and
      overall survival). Male breast carcinoma had worse disease-free survival than
      controls (P =.03). The clinical stage regardless of tumor size or lymph node
      metastasis was the single most significant prognostic factor (P <.0001). ER
      positive patients appeared to have a better survival than did ER-negative
      patients (P =.03, univariate; P not significant in multivariate) and did not
      benefit from treatment with tamoxifen (P =.0027, univariate; P =.42,
      multivariate). MiB1 and PR expressions did not correlate with treatment or
      survival, and p53 was associated with shorter disease free survival (P =.07,
      univariate; P =.047, multivariate). Stage for stage, Her2-neu was associated with
      shorter disease-free survival (P <.0001) and correlated with positive lymph nodes
      (P =.08). Surgery alone versus surgery with adjuvant treatments (chemotherapy,
      radiotherapy, tamoxifen, or combination) did not show any survival difference.
      Adjuvant therapy seemed to be associated with worse outcome. In the Veterans
      Administration hospital setting, the clinical stage and the expressions of p53
      and Her2-neu in male breast carcinoma may be prognostically useful markers in
      guiding future treatment in prospective studies, whereas ER, PR, and MiB1
      expressions are of limited value.

PMID- 12181272
TI  - Altered cellular distribution of tuberin and glucocorticoid receptor in sporadic
      fundic gland polyps.
AB  - Gastric fundic gland polyps (FGPs) are considered hamartomas, and various
      gastrointestinal hamartomas are associated with tuberous sclerosis complex (TSC).
      The aim of this study was to investigate a possible link between TSC proteins
      (hamartin and tuberin) and sporadic FGPs. We examined 33 sporadic FGPs and 26
      biopsies of normal fundic mucosa by immunohistochemistry. Nuclear
      immunoreactivity for tuberin was dramatically reduced or lost in most sporadic
      FGPs, and tuberin unexpectedly accumulated in the cytoplasm in oxyntic glands.
      About 18% (6/33) of FGPs were immunopositive in an average of 1.7% of oxyntic
      cell nuclei, compared with 77% (20/26) of controls in an average of 24.4% of
      oxyntic cell nuclei (P <.01). No change in hamartin was noted. We further
      examined the tuberin-associated proteins glucocorticoid receptor (GCR) and p27.
      Nuclear immunoreactivity for GCR was lost in most sporadic FGPs, but p27
      distribution was normal. Sporadic FGPs had a low frequency of staining for Ki-67
      except for some cells from cystic components, which is consistent with their slow
      growth. Our results are consistent with the hypothesis that tuberin may play an
      important role in pathogenesis of sporadic FGPs. First, an altered cellular
      localization of tuberin may lead to the deregulation of cell proliferation by
      interrupting its interaction with hamartin. Second, altered cellular localization
      of tuberin may preclude its negative regulation of gene transcription mediated by
      GCR.

PMID- 12181273
TI  - A rapid and reliable enzyme immunoassay PCR-based screening method to identify
      EBV-carrying gastric carcinomas.
AB  - Epstein-Barr virus (EBV) is associated with a substantial number of gastric
      adenocarcinomas worldwide, as confirmed by EBER1/2-RNA in situ hybridization
      (RISH). In the present study, we developed a rapid and sensitive PCR-based
      prescreening method for the detection of EBV in gastric carcinomas to reduce the
      amount of laborious EBER1/2-RISH assays to be performed. The method was evaluated
      by testing gastric adenocarcinomas (n = 242) using both BamHI W PCR-enzyme
      immunoassay (EIA) and EBER1/2-RISH, in combination with appropriate DNA and RNA
      quality controls. Seventy-four percent of the paraffin-embedded gastric
      adenocarcinomas had good DNA quality as shown by beta-globin polymerase chain
      reaction (PCR) after proteinase K and boiling pretreatment, whereas after DNA
      purification this was increased to 90%. Thirty-two percent of all cases were EBV
      DNA positive after PCR-EIA, whereas 10% of these gastric cancers contained EBV
      transcripts in the neoplastic cells as confirmed by EBER1/2-RISH. Interestingly,
      only samples with high optical density (OD) 405/630 values in PCR-EIA, equivalent
      to the maximum reading of the assay as determined by the positive control,
      contained EBV-positive tumor cells in the EBER1/2-RISH. In contrast, the weak
      positive samples, as determined by low OD readings in the PCR-EIA were EBER1/2
      RISH negative. In conclusion, high OD values in EBV PCR-EIA are very valuable to
      prescreen EBV-carrying gastric carcinomas as confirmed by EBER1/2-RISH. Only
      these samples and those with poor DNA quality will require testing in the EBER1/2
      RISH, thereby reducing the amount of laborious RISH assays with 85%.

PMID- 12181274
TI  - Molecular analysis of p53, MDM2, and H-ras genes in osteosarcoma and malignant
      fibrous histiocytoma of bone in patients older than 40 years.
AB  - Some investigators have reported that the histological features of osteosarcoma
      (OS) arising in elderly patients are different from those in younger patients;
      however, a molecular biologic study of OS in elderly patients has not been
      documented. In this study, 23 cases of OS (15 osteoblastic and 8 MFH-like types)
      and 18 cases of MFH of bone in patients 40 years of age or older were analyzed
      for mutation of the p53 gene, amplification of the MDM2 gene, and mutation of the
      H-ras gene, using formalin-fixed paraffin-embedded materials. We also examined
      the expression of p53, MDM2, and p21WAF1 protein immunohistochemically and
      assessed the proliferative activities using the monoclonal antibody MIB-1. p53
      immunoreactivity was recognized in 5 of 23 OS cases (22%), whereas p53 gene
      mutations were also detected in 5 of 23 OS cases (22%; osteoblastic [4/15; 27%]
      and MFH-like [1/8; 18%] types) and in 4 of 18 cases of MFH of bone (22%). There
      was a statistically significant correlation between p53 immunoreactivity and p53
      mutation status in OS (P =.0482). All those cases of osteoblastic OS and MFH of
      bone that had p53 mutations, with the exception of one case of MFH of bone that
      had a silent mutation, showed aggressive biologic behavior (dead of disease
      within 12 mo), in contrast to the MFH-like OS cases (alive without disease at 22
      mo). Three cases of OS (13%) and three cases of MFH of bone (17%) showed
      immunoreactivity for MDM2. As for gene alteration, three cases of OS (13%) and 3
      cases of MFH of bone (17%) demonstrated MDM2 amplification. MDM2 amplification
      showed a significant correlation with the expression of MDM2 protein in OS (P
      =.0344). p21WAF1 expression was detected in three cases of OS (13%) and in six
      cases of MFH of bone (33%). MDM2 alteration and p21WAF1 expression were not
      observed in any of the cases of MFH-like OS. MIB-1-LI showed a statistically
      significant correlation with p53 immunoreactivity and MDM2 immunoreactivity in OS
      (P =.0307 and P =.0358, respectively). H-ras mutation at Codons 12 and 13 was not
      recognized in any of the cases of OS or MFH of bone. In conclusion, although
      treatment differences during the time of study make it difficult to compare
      survival analysis, in the current study, p53 mutation in osteoblastic OS and MFH
      of bone in elderly patients seemed to be closely associated with the progression
      of the tumor, which was not the case in MFH-like OS. Furthermore, MDM2 alteration
      and p21WAF1 expression were demonstrated only in osteoblastic OS and MFH of bone,
      whereas they were not recognized in MFH-like OS. Although the number of patients
      in this analysis was small, it would appear that MFH-like OS may have some
      characteristic biologic aspects when compared with osteoblastic OS and MFH of
      bone in elderly patients.

PMID- 12181275
TI  - An efficient method for the assessment of DNA quality of archival microdissected
      specimens.
AB  - There will be an increasing need of methods for assessing the suitability of
      specimens for genetic-based assays as DNA markers become an integral part of
      molecular diagnosis. The targeting of specimens for specific analyses will
      require the ability to rapidly screen for DNA quality. Conventional methods such
      as Southern analysis and gene specific-polymerase chain reaction (PCR) often
      require quantities of material that represent a significant portion of the
      specimen, especially in microdissected samples. Here we describe a novel
      application of a commonly used PCR-based DNA-fingerprinting technology that
      requires minimal quantities of DNA to simultaneously assess multiple regions
      throughout the genome for DNA quality. Randomly amplified polymorphic DNA (RAPD)
      PCR generates DNA fragments of a broad size range with the product size
      reflecting the degree of sample fragmentation. Fourteen DNA samples extracted
      from cells microdissected from seven formalin-fixed, paraffin-embedded oral
      cancer biopsies were assessed for DNA quality using gene-specific PCR and RAPD
      PCR. Although the more conventional assay required 2-ng DNA (or 300-cell
      equivalents) to examine DNA quality at a single locus, RAPD-PCR provided a more
      informative profile of DNA quality from the same microdissected archival
      specimens.

PMID- 12181276
TI  - Back to the salt mines-- endothelial dysfunction in hypertension and compensatory
      role of endothelium-derived hyperpolarizing factor (EDHF).

PMID- 12181277
TI  - Application of physiological genomics to the study of hearing disorders.
AB  - Although the biophysical principles of how the ear operates are reasonably well
      understood, little is known about the specific genes that confer normal function
      to the inner ear. Nevertheless, the recent implementation of genomic tools has
      led to extraordinary progress in the identification of mutated genes that cause
      non-syndromic and syndromic forms of deafness. Part of this success is directly
      related to the sequencing of the human and mouse genomes and improved gene
      annotation methods. This review discusses how physiological genomic tools, such
      as genomic databases, expressed sequence tag databases and DNA arrays have been
      applied to find candidate genes for important molecular processes in the inner
      ear. It also illustrates, using the discovery of genes encoding essential
      components of cochlear K+ homeostasis as an example, how the combination of
      physiological genomic tools with physiological and morphological information has
      led to an in-depth understanding of cochlear ion homeostasis. Finally, it
      discusses how the use of applied genomic tools, such as gene arrays, will further
      advance our knowledge of how the inner ear works, develops, ages and regenerates.

PMID- 12181278
TI  - Cellular mechanisms for apical ATP effects on intracellular pH in human bronchial
      epithelium.
AB  - The effect of external ATP on intracellular pH (pH(i)) was investigated using a
      pH imaging system in a human bronchial epithelial cell line (16HBE14o-) loaded
      with BCECF-AM. The steady-state pH(i) of 16HBE14o- epithelial monolayers was
      7.137 +/- 0.027 (n = 46). Apical addition of ATP (10(-4) M) to epithelial
      monolayers induced a rapid and sustained pH(i) decrease of 0.164 +/- 0.024 pH
      units (n = 17; P < 0.001). The intracellular acidification was rapidly reversed
      upon removal of external ATP. In contrast, the non-hydrolysable ATP analogue AMP
      PNP did not produce any significant change in pH(i). Inhibition of
      purinoreceptors by suramin did not affect the acidification induced by apical
      ATP. Inhibition of Na+-H+ exchange by apical Na+ removal or addition of amiloride
      (0.5 mM) reduced the apical ATP-induced pH(i) decrease, suggesting the
      involvement of a Na+-H+ exchanger or surface pH effects on the ATP-induced pH(i)
      response. Inhibitors of proton channels such as ZnCl2 (10(-4) M) also partially
      inhibited the ATP response. The pH(i) response to ATP was dependent on the
      external pH (pH(o)), with increasing acidification produced at lower pH(o)
      values. Neither the basal pH(i) nor the ATP-induced intracellular acidification
      was affected by thapsigargin (a Ca2+-ATPase inhibitor), chelerythrine chloride (a
      protein kinase C (PKC) inhibitor), RpcAMP (a protein kinase A (PKA) inhibitor) or
      PMA (a PKC activator). Therefore, the intracellular acidification of human
      bronchial epithelial cells induced by apical ATP does not involve signalling via
      Ca2+, PKC or PKA nor binding to a purinoreceptor. We interpret the effect of ATP
      to produce an intracellular acidification as a three step process: activation of
      H+ channels, inhibition of Na+-H+ exchange and influx of protonated ATP.

PMID- 12181279
TI  - Non-ionotropic cross-talk between AMPA and NMDA receptors in rodent hippocampal
      neurones.
AB  - Many fast excitatory synapses in the hippocampus are enriched with both AMPARs
      (alpha-amino-3-hydroxyl-5-methyl-4-isoxazolepropionate receptors) and NMDARs (N
      methyl-D-aspartate receptors). Their proximity allows them to be activated
      simultaneously by the same neurotransmitter, L-glutamate. Activation of AMPARs
      leads to influx of sodium and calcium ions, which can increase or decrease NMDAR
      activity through sodium concentration-dependent cascades or a calcium-calmodulin
      dependent inactivation process, respectively. Here we provide evidence that the
      activation of AMPARs inhibits NMDARs through a non-ionotropic mechanism. NMDA
      induced current in isolated rat CA1 hippocampal cells and nucleated patches of
      cultured mouse hippocampal neurones decreased when AMPARs were activated.
      Conversely, when AMPARs were blocked, the NMDA component of glutamate-induced
      current increased. The inhibitory action of AMPAR activation on NMDAR-mediated
      current depends upon the open state of AMPA channels and rapidly diminishes after
      deactivation of AMPARs. The inhibitory action was independent of membrane
      voltage, univalent cation fluxes and calcium influx. The AMPA-NMDA cross
      inhibition also occurred in evoked synaptic current in CA1 neurones from intact
      mouse hippocampal slices. This cross-talk may play a role in preventing
      overexcitation during bursting activities in the hippocampus.

PMID- 12181280
TI  - Zn2+ currents are mediated by calcium-permeable AMPA/kainate channels in cultured
      murine hippocampal neurones.
AB  - Permeation of the endogenous cation Zn2+ through calcium-permeable AMPA/kainate
      receptor-gated (Ca-A/K) channels might subserve pathological and/or physiological
      signalling roles. Voltage-clamp recording was used to directly assess Zn2+ flux
      through these channels on cultured murine hippocampal neurones. Ca-A/K channels
      were present in large numbers only on a minority of neurones (Ca-A/K+ neurones),
      many of which were GABAergic. The presence of these channels was assessed in
      whole-cell or outside-out patch recording as the degree of inward rectification
      of kainate-activated currents, quantified via a rectification index (RI = G+40/G
      60), which ranged from <0.4 (strongly inwardly rectifying) to >2 (outwardly
      rectifying). The specificity of a low RI as an indication of robust Ca-A/K
      channel expression was verified by two other techniques, kainate-stimulated
      cobalt-uptake labelling, and fluorescence imaging of kainate-induced increases in
      intracellular Ca2+. In addition, the degree of inward rectification of kainate
      activated currents correlated strongly with the positive shift of the reversal
      potential (V(rev)) upon switching to a sodium-free, 10 mM Ca2+ buffer. With Zn2+
      (3 mM) as the only permeant extracellular cation, kainate-induced inward currents
      were only observed in neurones that had previously been identified as Ca-A/K+. A
      comparison between the V(rev) observed with 3 mM Zn2+ and that observed with Ca2+
      as the permeant cation revealed a P(Ca)/P(Zn) of approximately 1.8. Inward
      currents recorded in 3 mM Ca2+ were unaffected by the addition of 0.3 mM Zn2+,
      while microfluorimetrically detected increases in the intracellular concentration
      of Zn2+ in Ca-A/K+ neurones upon kainate exposure in the presence of 0.3 mM Zn2+
      were only mildly attenuated by the addition of 1.8 mM Ca2+. These results provide
      direct evidence that Zn2+ can carry currents through Ca-A/K channels, and that
      there is little interference between Ca2+ and Zn2+ in permeating these channels.

PMID- 12181281
TI  - Dynamic representation of whisker deflection by synaptic potentials in spiny
      stellate and pyramidal cells in the barrels and septa of layer 4 rat
      somatosensory cortex.
AB  - Whole-cell voltage recordings were made in vivo from excitatory neurons (n = 23)
      in layer 4 of the barrel cortex in urethane-anaesthetised rats. Their receptive
      fields (RFs) for a brief whisker deflection were mapped, the position of the cell
      soma relative to barrel borders was determined for 15 cells and dendritic and
      axonal arbors were reconstructed for all cells. Three classes of neurons were
      identified: spiny stellate cells and pyramidal cells located in barrels and
      pyramidal cells located in septa. Dendritic and, with some exceptions, axonal
      arborisations of barrel cells were mostly restricted to the borders of a column
      with a cross sectional area of a barrel, defining a cytoarchitectonic barrel
      column. Dendrites and axons of septum cells, in contrast, mostly extended across
      barrel borders. The subthreshold RFs measured by evoked postsynaptic potentials
      (PSPs) comprised a principal whisker (PW) and several surround whiskers (SuWs)
      indicating that deflection of a single whisker is represented in multiple barrels
      and septa. Barrel cells responded with larger depolarisation to stimulation of
      the PW (13.7 +/- 4.6 mV (mean +/- S.D.), n = 10) than septum cells (5.7 +/- 2.4
      mV, n = 5), the gradient between peak responses to PW and SuW deflection was
      steeper and the latency of depolarisation onset was shorter (8 +/- 1.4 ms vs. 11
      +/- 2 ms). In barrel cells the response onset and the peak to SuW deflection was
      delayed depending on the distance to the PW thus indicating that the spatial
      representation of a single whisker deflection in the barrel map is dynamic and
      varies on the scale of milliseconds to tens of milliseconds. Septum cells
      responded later and with comparable latencies to PW and SuW stimulation.
      Spontaneous (0.053 +/- 0.12 action potentials (APs) s(-1)) and evoked APs (0.14
      +/- 0.29 APs per principal whisker (PW) stimulus) were sparse. We conclude that
      PSPs in ensembles of barrel cells represent dynamically the deflection of a
      single whisker with high temporal and spatial acuity, initially by the excitation
      in a single PW-barrel followed by multi-barrel excitation. This presumably
      reflects the divergence of thalamocortical projections to different barrels.
      Septum cell PSPs preferably represent multiple whisker deflections, but less
      dynamically and with less spatial acuity.

PMID- 12181282
TI  - Role of outer ring carboxylates of the rat skeletal muscle sodium channel pore in
      proton block.
AB  - Voltage-gated Na+ current is reduced by acid solution. Protons reduce peak Na+
      conductance by lowering single channel conductance and shift the voltage range of
      gating by neutralizing surface charges. Structure-function studies identify six
      carboxyls and a lysine in the channel's outer vestibule. We examined the roles of
      the superficial ring of carboxyls in acid block of Na(v)1.4 (the rat skeletal
      muscle Na+ channel isoform) by measuring the effects of their neutralization or
      their substitution by lysine on sensitivity to acid solutions, using the two
      micropipette voltage clamp in Xenopus oocytes. Alteration of the outer ring of
      carboxylates had little effect on the voltage for half-activation of Na+ current,
      as if they are distant from the channels' voltage sensors. The mutations did not
      abolish proton block; rather, they all shifted the pK(a) (-log of the
      dissociation constant) in the acid direction. Effects of neutralization on pK(a)
      were not identical for different mutations, with E758Q > D1241A > D1532N > E403Q.
      E758K showed double the effect of E758Q, and the other lysine mutations all
      produced larger effects than the neutralizing mutations. Calculation of the
      electrostatic potential produced by these carboxylates using a pore model showed
      that the pK(a) values of carboxylates of Glu-403, Glu-758, and Asp-1532 are
      shifted to values similar to the experimentally measured pK(a). Calculations also
      predict the experimentally observed changes in pK(a) that result from mutational
      neutralization or introduction of a positive charge. We propose that proton block
      results from partial protonation of these outer ring carboxylates and that all of
      the carboxylates contribute to a composite Na+ site.

PMID- 12181283
TI  - Neuropeptide Y inhibits axonal transport of particles in neurites of cultured
      adult mouse dorsal root ganglion cells.
AB  - Neuropeptide Y (NPY) plays a modulatory role in processing nociceptive
      information. The present study investigated the effects of NPY on axonal
      transport of particles in neurites of cultured adult dorsal root ganglion (DRG)
      cells using video-enhanced microscopy. Application of NPY decreased the number of
      particles transported in both the anterograde and retrograde directions. This
      effect was persistently observed during NPY application and was reversed after
      washout. The inhibitory effect of NPY was concentration dependent between 10(-9)
      M and 10(-6) M. The instantaneous velocity of individual particles moving in
      anterograde and retrograde directions was also reduced by NPY. Both the NPY Y1
      receptor agonist [Leu31,Pro34]-NPY and NPY Y2 receptor agonist NPY(13-36)
      mimicked the effect of NPY on the number of transported particles. An
      immunocytochemical study using an antiserum against the NPY Y1 receptor protein
      revealed that the Y1 receptor was expressed in the majority (85.9 %) of cultured
      adult mouse DRG cells. Pre-treatment of cells with pertussis toxin, a GTP-binding
      protein (G protein) inhibitor, completely blocked the inhibitory effect of NPY.
      Each application of SQ-22536, an adenylate cyclase inhibitor, and H-89, a protein
      kinase A inhibitor, mimicked and occluded the effect of NPY. In contrast,
      dibutyryl cAMP (dbcAMP), a membrane permeable cAMP analogue, and forskolin, an
      activator of adenylate cyclase, produced a transient increase in axonal
      transport. The application of dbcAMP and forskolin in combination with NPY
      negated the effect of NPY alone. These results suggest that NPY, acting at Y1 and
      Y2 receptors, inhibits axonal transport of particles in sensory neurones. The
      effect seems to be mediated by a pertussis toxin-sensitive G protein, adenylate
      cyclase, and protein kinase A pathway. Therefore, NPY may be a modulatory factor
      for axonal transport in sensory neurones.

PMID- 12181284
TI  - Presynaptic and postsynaptic mechanisms underlie paired pulse depression at
      single GABAergic boutons in rat collicular cultures.
AB  - Paired pulse depression (PPD) is a common form of short-term synaptic plasticity.
      The aim of this study was to characterise PPD at the level of a single inhibitory
      bouton. Low-density collicular cultures were loaded with the Ca2+ indicator
      Oregon Green-1, active boutons were stained with RH414, and action potentials
      were blocked with TTX. Evoked IPSCs (eIPSCs) and presynaptic Ca2+ transients were
      recorded in response to direct presynaptic depolarisation of an individual
      bouton. The single bouton eIPSCs had a low failure rate (< 0.1), large average
      quantal content (3-6) and slow decay (tau(1) = 15 ms, tau(2) = 81 ms). The PPD of
      eIPSCs had two distinct components: PPD(fast) and PPD(slow) (tau = 86 ms and 2
      s). PPD(slow) showed no dependence on extracellular Ca2+ concentration, or on the
      first eIPSC's failure rate or amplitude. Most probably, it reflects a release
      independent inhibition of exocytosis. PPD(fast) was only observed in normal or
      elevated Ca2+. It decreased with the failure rate and increased with the
      amplitude of the first eIPSC. It coincided with paired pulse depression of the
      presynaptic Ca2+ transients (tau = 120 ms). The decay of the latter was
      accelerated by EGTA, which also reduced PPD(fast). Therefore, a suppressive
      effect of residual presynaptic Ca2+ on subsequent Ca2+ influx is considered the
      most likely cause of PPD(fast). PPD(fast) may also have a postsynaptic component,
      because exposure to a low-affinity GABA(A) receptor antagonist (TPMPA; 300
      microM) counteracted PPD(fast), and asynchronous IPSC amplitudes were depressed
      for a short interval following an eIPSC. Thus, at these synapses, PPD is produced
      by at least two release-independent presynaptic mechanisms and one release
      dependent postsynaptic mechanism.

PMID- 12181286
TI  - In vitro and in vivo analysis of the effects of corticotropin releasing factor on
      rat dorsal vagal complex.
AB  - In vivo and in vitro electrophysiological experiments were performed on the rat
      dorsal vagal complex (DVC, i.e. nucleus of the tractus solitarius, NTS, and
      dorsal motor nucleus of the vagus, DMV) to examine the effects of corticotropin
      releasing hormone (CRF) on the central components of the vago-vagal reflex
      control of gastric function. When applied to gastrointestinal projecting DMV
      neurones, CRF (10-300 nM) induced a concentration-dependent membrane
      depolarization, an increase in action potential firing rate and decrease in
      amplitude of the action potential afterhyperpolarization (P < 0.05). Pretreatment
      with the non-selective CRF antagonist, astressin (0.5-1 microM) or the selective
      CRF(2) receptor antagonist, astressin 2B (500 nM) attenuated the CRF-induced
      increase in firing rate but did not alter basal discharge rate. CRF (30-300 nM)
      increased the amplitude of excitatory postsynaptic currents (EPSCs) evoked by
      stimulation of the NTS (P < 0.05). An alteration in the paired pulse ratio
      indicated the EPSC's increase occurred due to actions at presynaptic sites. In
      the in vivo anaesthetized rat preparation, bilateral microinjections (20 fmol in
      20 nl for each site) of CRF in the DVC decreased gastric motility in rats
      pretreated with the muscarinic agonist, bethanecol (P < 0.05). The effects of CRF
      were abolished by systemic administration of the NOS inhibitor, L-NAME, or by
      bilateral vagotomy. We concluded that CRF had both a direct and an indirect
      excitatory effect on DMV neurones via activation of CRF(2) receptors and the
      decrease in gastric motility observed following microinjection of CRF in the DVC
      is due to the activation of an inhibitory non-adrenergic non-cholinergic input to
      the gastrointestinal tract.

PMID- 12181285
TI  - Organic cation transporter mRNA and function in the rat superior cervical
      ganglion.
AB  - Reuptake of extracellular noradrenaline (NA) into superior cervical ganglion
      (SCG) neurones is mediated by means of the noradrenaline transporter (NAT, uptake
      1). We now demonstrate by single-cell RT-PCR that mRNA of the organic cation
      transporter 3 (OCT3, uptake 2) occurs in rat SCG neurones as well. Furthermore,
      our RT-PCR analyses reveal the presence of mRNA for novel organic cation
      transporters 1 and 2 (OCTN1 and OCTN2), but not for OCT1 or OCT2 in the ganglion.
      Making use of the NAT as a powerful, neurone-specific transporter system, we
      loaded[3H]-N-methyl-4-phenylpyridinium ([3H]-MPP+) into cultured rat SCG
      neurones. The ensuing radioactive outflow from these cultures was enhanced by
      desipramine and reserpine, but reduced (in the presence of desipramine) by the
      OCT3 inhibitors cyanine 863, oestradiol and corticosterone. In contrast, cyanine
      863 enhanced the radioactive outflow from cultures preloaded with [3H]-NA. Two
      observations suggest that a depletion of storage vesicles by cyanine 863 accounts
      for the latter phenomenon: first, the primary radioactive product isolated from
      supernatants of cultures loaded with [3H]-NA was the metabolite [3H]-DHPG; and
      second, inhibition of MAO significantly reduced the radioactive outflow in
      response to cyanine 863. The outflow of [3H]-MPP+ was significantly enhanced by
      MPP+, guanidine, choline and amantadine as potential substrates for OCT-related
      transmembrane transporters. However, desipramine at a low concentration
      essentially blocked the radioactive outflow induced by all of these substances
      with the exception of MPP+, indicating the NAT and not an OCT as their primary
      site of action. The MPP+-induced release of [3H]-MPP+ was fully prevented by a
      combined application of desipramine and cyanine 863. No trans-stimulation of [3H]
      MPP+ outflow was observed by the OCTN1 and OCTN2 substrate carnitine at 100
      microM. Our observations indicate an OCT-mediated transmembrane transport of [3H]
      MPP+. Amongst the three OCTs expressed in the SCG, OCT3 best fits the profile of
      substrates and antagonists that cause trans-stimulation and trans-inhibition,
      respectively, of [3H]-MPP+ release.

PMID- 12181287
TI  - Relationship between intracellular ionic strength and expression of tonicity
      responsive genes in rat papillary collecting duct cells.
AB  - Intracellular ionic strength may play an important role in regulating the
      expression of genes encoding osmolyte-accumulating molecules. To establish
      whether a strict relation exists between these variables, intracellular ionic
      strength (sum of Na+, Cl- and K+ concentrations) and the relative abundance of
      mRNA derived from various tonicity-sensitive genes was examined using electron
      microprobe analysis and Northern blots on primary cultures of rat papillary
      collecting duct (PCD) cells following acute or long-term alterations in medium
      tonicity. Hypertonic medium (450 mosmol kg(-1)) evoked an initial rise in
      intracellular ionic strength (269 +/- 5 vs. 194 +/- 7 mmol (kg wet weight (wt))(
      1) in isotonic controls; means +/- S.E.M.), which subsequently declined
      gradually, and a significantly higher abundance of bgt1 (Na+- and Cl- -dependent
      betaine transporter), smit (Na+/myo-inositol cotransporter), ar (aldose
      reductase) and osp94 (osmotic stress protein 94) mRNAs. Conversely, exposure to
      hypotonic medium (200 mosmol kg(-1)) for 12 h was associated with significantly
      reduced intracellular ionic strength (153 +/- 4 mmol (kg wet wt)(-1)) and
      significantly reduced the abundance of smit and ar mRNAs. PCD cells
      preconditioned in hypotonic medium and re-exposed to isotonic medium showed
      significantly higher abundance of these mRNAs than isotonic controls, although
      the intracellular ionic strength did not differ. Two further tonicity-sensitive
      genes responded differently to medium tonicity: while the abundance of hsp70
      (heat shock protein 70) mRNA increased significantly following both hypo- and
      hypertonic stress, inos (inducible nitric oxide synthase) mRNA abundance
      correlated inversely with medium tonicity. These findings support the view that
      the effect of intracellular ionic strength on the expression of bgt1, smit, ar
      and osp94 is modulated by additional factors such as cell volume, and that its
      effect on the pathways regulating hsp70 and inos is even more complex.

PMID- 12181289
TI  - Excitation-contraction coupling and sarcoplasmic reticulum function in
      mechanically skinned fibres from fast skeletal muscles of aged mice.
AB  - Ageing is generally associated with a decline in skeletal muscle mass and
      strength, and a slowing of muscle contraction, factors that impact upon the
      quality of life for the elderly. Alterations in Ca2+ handling are thought to
      contribute to these age-related changes in muscle contractility, yet the effects
      of ageing on sarcoplasmic reticulum (SR) Ca2+ handling and the Ca2+ transport
      system remain unresolved. We used mechanically skinned single fibres from the
      fast twitch extensor digitorum longus (EDL) muscles from young (4-month-old) and
      old (27- to 28-month-old) mice to test the hypothesis that the age-related
      changes in skeletal muscle contractility, especially the slower rate of
      contraction, are due to changes intrinsic to the muscle fibres. There were no age
      related differences in the peak height of depolarization-induced contractile
      response (DICR) or the number of DICRs elicited before rundown (DICR < 50 % of
      initial). The time taken to reach peak DICR (TPDICR) was approximately12 % slower
      in single muscle fibres from old compared with young mice (P < 0.05). The rate of
      relaxation following DICR was not different in young and old mice. Examination of
      SR function demonstrated that SR Ca2+ reloading in Ca2+ -depleted skinned fibres
      was not different in young and old mice, nor was there any age-related difference
      in Ca2+ leak from the SR. However, low [caffeine] contracture in fibres from old
      mice was only half of that observed in fibres from young mice (P < 0.05),
      indicating a lower sensitivity of the SR Ca2+ release channel (CRC) to caffeine.
      We found no difference in maximum Ca2+ -activated force (P(o)) or specific force
      (sP(o); P(o) corrected for cross-sectional area) in EDL muscle fibres from young
      and old mice. Impaired excitation-contraction (E-C) coupling and a decrease in SR
      CRC function are mechanisms which are likely to contribute to the overall slowing
      of muscle contraction with age.

PMID- 12181288
TI  - Excitation of smooth muscles isolated from the guinea-pig gastric antrum in
      response to depolarization.
AB  - In small segments of circular smooth muscle bundle isolated from the guinea-pig
      gastric antrum, depolarization of the tissue with intracellular current stimuli
      evoked regenerative slow potentials after a refractory period of 5-10 s. The
      refractory period changed inversely with the amplitude and duration of the
      stimulating depolarization. Thapsigargin (an inhibitor of calcium-ATPase at
      internal stores), 2-aminoethoxydiphenyl borate (2-APB, an inhibitor of inositol
      1,4,5-trisphosphate (IP3)-receptor-mediated Ca2+ release), and carbonyl cyanide m
      chlorophenyl-hydrazone (a mitochondrial protonophore) reduced the amplitude of
      slow potentials, with no significant alteration of the refractory period.
      Bisindolylmaleimide I or chelerythrine (inhibitors of protein kinase C, PKC)
      increased the refractory period and inhibited the amplitude of slow potentials.
      These results indicate that the refractory period and amplitude of slow
      potentials are related to the activation of PKC and the amount of Ca2+ released
      from the internal stores through activation of IP3 receptors, respectively.
      Acetylcholine (ACh) reduced the refractory period and increased the amplitude of
      slow potentials: the former was antagonized by chelerythrine and the latter by 2
      APB. The results suggest that ACh has dual actions; stimulation of the metabolism
      of inositol phosphate and activation of PKC. Phorbol-12-myristate-13-acetate, a
      selective stimulant of PKC, at low concentrations (< 10 nM) mimicked the actions
      of ACh and at high concentrations reduced the frequency of slow potentials and
      increased the refractory period. The possible involvement of the concentration
      dependent differences in the actions of phorbol ester on the translocation of PKC
      was considered.

PMID- 12181290
TI  - The mechanism of the force enhancement by MgADP under simulated ischaemic
      conditions in rat cardiac myocytes.
AB  - In this study, the effects of MgADP and/or MgATP on the Ca2+ -dependent and Ca2+ 
      independent contractile force restoration were determined in order to identify
      the origin of the tonic force increase (i.e. ischaemic contracture) which
      develops during advanced stages of ischaemia. Experiments were performed at 15
      degrees C during simulated ischaemic conditions in Triton-skinned right
      ventricular myocytes from rats. In the presence of 5 mM MgATP the maximal Ca2+ 
      dependent force (P(o)) of 39 +/- 2 kN m(-2) (mean +/- S.E.M.) under control
      conditions (pH 7.0, 15 mM phosphocreatine (CP)) decreased to 8 +/- 1 % during
      simulated ischaemia (pH 6.2, 30 mM inorganic phosphate (P(i)), without CP). This
      change was accompanied by a major reduction in Ca2+ sensitivity (pCa(50) 4.10 vs.
      5.62). Substitution of MgADP for MgATP restored isometric force production and
      its Ca2+ sensitivity (pCa(50) 4.74 at 4 mM MgADP and 1 mM MgATP). In addition, it
      shifted the MgATP threshold concentration of Ca2+ -independent force development
      to higher levels in a concentration-dependent manner. However, Ca2+ -independent
      force was facilitated less by MgADP than Ca2+ -dependent force. The MgADP-induced
      increase in force was accompanied by marked reductions in the velocity of
      unloaded shortening and the rate of tension redevelopment. These data and
      simulations using a model of cross-bridge kinetics suggest that the ischaemic
      force is not a consequence of a reduction in intracellular MgATP concentration,
      but identify MgADP as a key modulator of the cross-bridge cycle under simulated
      ischaemic conditions in cardiac muscle, with a much lower inhibition constant
      (0.012 +/- 0.003 mM) than in skeletal muscle. Therefore, MgADP has a high
      potential to stabilize the force-generating cross-bridge state and to facilitate
      the development of ischaemic contracture, possibly involving a Ca2+ activation
      process in the ischaemic myocardium.

PMID- 12181291
TI  - Physical activity changes the regulation of mitochondrial respiration in human
      skeletal muscle.
AB  - This study explores the importance of creatine kinase (CK) in the regulation of
      muscle mitochondrial respiration in human subjects depending on their level of
      physical activity. Volunteers were classified as sedentary, active or athletic
      according to the total activity index as determined by the Baecke questionnaire
      in combination with maximal oxygen uptake values (peak V(O2), expressed in ml
      min(-1) kg(-1)). All volunteers underwent a cyclo-ergometric incremental exercise
      test to estimate their peak V(O2) and V(O2) at the ventilatory threshold (VT).
      Muscle biopsy samples were taken from the vastus lateralis and mitochondrial
      respiration was evaluated in an oxygraph cell on saponin permeabilised muscle
      fibres in the absence (V(0)) or in the presence (V(max)) of saturating [ADP].
      While V(0) was similar, V(max) differed among groups (sedentary, 3.7 +/- 0.3,
      active, 5.9 +/- 0.9 and athletic, 7.9 +/- 0.5 micromol O2 min(-1) (g dry weight)(
      1)). V(max) was correlated with peak V(O2) (P < 0.01, r = 0.63) and with V(T) (P
      < 0.01, r = 0.57). There was a significantly greater degree of coupling between
      oxidation and phosphorylation (V(max)/V(0)) in the athletic individuals. The
      mitochondrial K(m) for ADP was significantly higher in athletic subjects (P <
      0.01). Mitochondrial CK (mi-CK) activation by addition of creatine induced a
      marked decrease in K(m) in athletic individuals only, indicative of an efficient
      coupling of mi-CK to ADP rephosphorylation in the athletic subjects only. It is
      suggested that increasing aerobic performance requires an enhancement of both
      muscle oxidative capacity and mechanisms of respiratory control, attesting to the
      importance of temporal co-ordination of energy fluxes by CK for higher efficacy.

PMID- 12181292
TI  - Oxidant stress stimulates anion secretion from the human airway epithelial cell
      line Calu-3: implications for cystic fibrosis lung disease.
AB  - Exposure to reactive oxygen species (ROS) is associated with tissue damage in the
      lung and may be a common element in the pathogenesis of all inflammatory lung
      diseases. Exposure to the ROS hydrogen peroxide (H2O2) evoked a rapid increase in
      transepithelial anion secretion across monolayers of the human submucosal gland
      serous cell line Calu-3. This increase was almost entirely abolished by the
      addition of diphenylamine-2-carboxylate (DPC), implicating the cystic fibrosis
      transmembrane conductance regulator (CFTR) Cl- channel in the response. The
      response was also reduced by inhibitors of basolateral K+ channels. Studies of
      electrically isolated apical and basolateral membranes revealed that H2O2
      stimulated both apical Cl- and basolateral K+ conductances (G(Cl) and G(K)).
      Apical G(Cl) was sensitive to DPC, but unaffected by 4,4'
      diisothiocyanatostilbene-2,2'-disulfonic acid (DIDS), suggesting that CFTR is the
      major anion conduction pathway mediating the response to H2O2. Additionally, H2O2
      had no effect on G(Cl) in the presence of the adenylate cyclase inhibitor SQ22536
      or following maximal stimulation of G(Cl) with forskolin, implicating the cAMP
      dependent protein kinase pathway in the apical response to H2O2. Basolateral G(K)
      was reduced by the K+ channel inhibitors clotrimazole and clofilium, indicating
      roles for KCNN4 and KCNQ1 in the H2O2-stimulated response. We propose that ROS
      stimulated anion secretion from serous cells plays an important role in keeping
      the airways clear from damaging radicals that could potentially initiate tissue
      destruction. Our finding that this response is CFTR dependent suggests that an
      important host defence mechanism would be dysfunctional in the cystic fibrosis
      (CF) lung. Loss of this compensatory protective mechanism could expose the CF
      lung to ROS for extended periods, which could be important in the pathogenesis of
      CF lung disease.

PMID- 12181293
TI  - Cold- and menthol-sensitive C afferents of cat urinary bladder.
AB  - Cold-sensitive C afferents of the urinary bladder were studied in adult cats
      anaesthetised with alpha-chloralose. The bladder was catheterised for fluid
      instillations and bladder pressure recordings. Pelvic nerve branches were
      stimulated electrically close to the bladder. Evoked afferent activity was
      recorded from dissected filaments of the ipsilateral S1-S2 dorsal roots.
      Responsive afferents were identified using the 'marking technique', based on
      activity-dependent decrease in C fibre conduction velocity. Of 108 examined
      bladder C afferents, 14 were activated by innocuous cooling of the bladder wall.
      Their conduction velocities ranged from 0.6 to 1.7 ms(-1) and their activity
      dependent decrease in conduction velocity was <10 %. All nine cold-sensitive
      afferents tested responded to menthol exposure. Cold-sensitive C afferents failed
      to respond to bladder filling with body-warm saline and to active bladder
      contractions. These characteristics indicate that the cold-sensitive C afferents
      of the bladder resemble cutaneous cold receptors rather than cold-sensitive
      mechanoreceptors or nociceptors. It is concluded that the bladder wall is endowed
      with cold receptors with unmyelinated C afferents in the pelvic nerves and that
      these afferents are responsible for the bladder cooling reflex.

PMID- 12181294
TI  - The release and vascular action of bradykinin in the isolated perfused bovine
      udder.
AB  - It has been postulated that the mammary kinin system may play a role in
      modulating mammary blood flow. Until the present study, the local release of
      bradykinin (BK) or other kinin system constituents into the mammary vasculature
      had not been reported and there were also conflicting findings on the action of
      BK on udder vasculature. Udders were removed from healthy lactating cows at
      slaughter. Pairs of ipsilateral quarters were perfused with Tyrode solution
      through the external pudendalis artery and drained via the cranial superficial
      epigastric vein. Mammary secretion was collected through teat cannulae. The
      perfusion pressure was linearly related to perfusate flux between 60 and 210 ml
      min(-1) and the flow rate was adjusted (110-150 ml min(-1)) to give a basal
      pressure of 85 mmHg. PO2, PCO2 and pH in the venous effluent perfusate stabilised
      at 157 +/- 10 mmHg, 50.1 +/- 2.4 mmHg and 7.1 +/- 0.03, respectively. The venous
      effluent contained immunoreactive BK and BK precursor, tissue kallikrein
      activity, and bradykinin-destroying enzyme. The concentration of BK stabilised at
      378 +/- 48 pg (ml perfusate)(-1), that of trypsin-activated BK precursor was 679
      +/- 59 pg BK equivalents ml(-1) and that of tissue kallikrein, measured as
      cleavage of D-Val.Leu.Arg-p-nitroanilide (D-Val.Leu.Arg-pNA), was 5.5 +/- 1.7
      nmol p-NA h(-1) ml(-1). Arterial infusion of phenylephrine (0.49-490 microM)
      produced increases in perfusion pressure (vasoconstriction). Acetylcholine (ACh)
      (0.55-55 microM) and BK (0.1-10 microM) produced only vasodilatation. BK (EC50 =
      1.00+/-0.04 microM) was a more potent vasodilator than ACh (EC50 = 9.57+/-0.49
      microM). The basal BK concentration was 250 times below the threshold for
      vasoactivity. The udder produced a milk-like secretion, which was dependent on
      perfusate flow and contained a concentration of BK which remained unchanged from
      60 to 180 min of perfusion (231 +/- 31 pg ml(-1)) unlike that in the venous
      effluent which doubled between 60 and 120 min. Thus, in addition to its secretion
      into milk, BK, together with its precursor and tissue kallikrein, is continuously
      released into the vasculature of the isolated, perfused, lactating bovine udder.

PMID- 12181295
TI  - Patterns of intracellular and intercellular Ca2+ waves in the longitudinal muscle
      layer of the murine large intestine in vitro.
AB  - Ca2+ wave activity was monitored in the longitudinal (LM) layer of isolated
      murine caecum and proximal colon at 35 degrees C with fluo-4 AM and an iCCD
      camera. Both intracellular (within LM cells) and intercellular (also spreading
      from cell to cell) Ca2+ waves were observed. Intracellular Ca2+ waves were
      associated with a lack of muscle movement whereas intercellular Ca2+ waves, which
      were five times more intense than intracellular waves, were often associated with
      localized contractions. Several intracellular Ca2+ waves were present at the same
      time in individual LM cells. Waves in adjacent LM cells were not coordinated and
      were unaffected by TTX (1 microM) but were blocked by IP3 receptor antagonists
      xestospongin-C (Xe-C; 2 microM) or 2-aminoethyl diphenylborate (2-APB; 25
      microM), and by ryanodine (10 microM). Caffeine (5 mM) restored wave activity
      following blockade with Xe-C. NiCl2 (1 mM) blocked intracellular Ca2+ waves, and
      nicardipine (2 microM) reduced their frequency and intensity, but did not affect
      their velocity, suggesting the sarcoplasmic reticulum may be fuelled by
      extracellular Ca2+ entry. Intercellular Ca2+ waves often occurred in bursts and
      propagated rapidly across sizeable regions of the LM layer and were blocked by
      heptanol (0.5 mM). Intercellular Ca2+ waves were dependent upon neural activity,
      external Ca2+ entry through L-type Ca2+ channels, and amplification via calcium
      induced calcium release (CICR). In conclusion, intracellular Ca2+ waves, which
      may reduce muscle excitability, are confined to individual LM cells. They depend
      upon Ca2+ release from internal Ca2+ stores and are likely to be fuelled by
      extracellular Ca2+ entry. Intercellular Ca2+ waves, which are likely to underlie
      smooth muscle tone, mixing and propulsion, depend upon neural activity, muscle
      action potential propagation and amplification by CICR.

PMID- 12181296
TI  - Change in endothelial function in mesenteric arteries of Sprague-Dawley rats fed
      a high salt diet.
AB  - A high salt diet in some species results in elevated arterial blood pressure and
      alterations in vascular smooth muscle responses to agonists. Weanling male
      Sprague-Dawley rats were given either a high salt diet containing 8 % or a low
      salt diet of 0.4 % sodium chloride for a period of 4 weeks. At the end of the
      feeding period, tail systolic pressure was higher in the high salt than in low
      salt rats. The rats were then killed and the intestines removed. Vascular smooth
      muscle (VSM) responses were estimated from the changes in lumenal diameter of
      pressurised second order mesenteric resistance arteries. High salt diet resulted
      in enhanced VSM responses to noradrenaline. The vessels dilated in response both
      to acetylcholine and to sodium nitroprusside and the responses were similar in
      vessels from both high and low salt rats. However, vessels from high salt rats
      were resistant to the blocking of endothelium derived nitric oxide (EDNO) with L
      NAME and the responses were instead abolished by blocking endothelium derived
      hyperpolarising factor (EDHF) with apamin and charybdotoxin. These results show
      that in Sprague-Dawley rats, a high salt diet enhances the vasoconstriction in
      response to noradrenaline. The vasodilatory responses to acetylcholine were not
      significantly changed. However, they appeared to be mediated mainly by EDHF
      rather than by EDNO as in the low salt animals.

PMID- 12181297
TI  - Nitric oxide-induced Cl- secretion in isolated rat colon is mediated by the
      release of thromboxane A2.
AB  - We have shown previously that thromboxane A2 (TXA2), which may be released by the
      anti-tumour drug irinotecan and by platelet-activating factor (PAF), causes Cl-
      secretion in the isolated rat colon. In the present study, the involvement of
      TXA2 in nitric oxide-induced Cl- secretion in isolated rat colon was
      investigated. In colonic mucosa set between Ussing chambers, the NO donor sodium
      nitroprusside (SNP; 100 microM) caused Cl- secretion, an effect that was almost
      completely inhibited by the NO scavenger carboxy-PTIO at 200 microM. The SNP
      induced Cl- secretion was inhibited in a concentration-dependent manner by the
      TXA2 receptor antagonist ONO-3708 (IC50 = 2 microM) and the TX synthase inhibitor
      Y-20811 (IC50 = 0.4 microM). SNP significantly increased the release of TXA2
      (measured as TXB2 release) from the mucosa. The SNP-induced increases in Cl-
      secretion and TXA2 release were blocked by a NO-sensitive guanylate cyclase
      inhibitor (ODQ). Dibutyryl cGMP (500 microM) also induced Cl- secretion, which
      was sensitive to ONO-3708 (10 microM) and Y-20811 (1 microM), and increased the
      release of TXA2 from the mucosa. PAF-induced (10 microM) Cl- secretion was
      inhibited by carboxy-PTIO (200 microM) and ODQ (10 microM), whereas irinotecan
      induced (500 microM) Cl- secretion was not significantly inhibited by these
      drugs. A stable TXA2 analogue (STA2) but not SNP (100 microM) changed the
      membrane potential of epithelial cells in isolated colonic crypts under the whole
      cell current-clamp condition. These results indicate that PAF elicits the NO-cGMP
      pathway and then stimulates the release of TXA2, which is a stimulant of colonic
      Cl- secretion. In contrast, the NO-cGMP pathway is not involved in the TXA2
      mediated Cl- secretion induced by irinotecan.

PMID- 12181298
TI  - Static gamma-motoneurones couple group Ia and II afferents of single muscle
      spindles in anaesthetised and decerebrate cats.
AB  - Ideas about the functions of static gamma-motoneurones are based on the responses
      of primary and secondary endings to electrical stimulation of single static gamma
      axons, usually at high frequencies. We compared these effects with the actions of
      spontaneously active gamma-motoneurones. In anaesthetised cats, afferents and
      efferents were recorded in intramuscular nerve branches to single muscle
      spindles. The occurrence of gamma-spikes, identified by a spike shape recognition
      system, was linked to video-taped contractions of type-identified intrafusal
      fibres in the dissected muscle spindles. When some static gamma-motoneurones were
      active at low frequency (< 15 Hz) they coupled the firing of group Ia and II
      afferents. Activity of other static gamma-motoneurones which tensed the
      intrafusal fibres appeared to enhance this effect. Under these conditions the
      secondary ending responded at shorter latency than the primary ending. In another
      series of experiments on decerebrate cats, responses of primary and secondary
      endings of single muscle spindles to activation of gamma-motoneurones by natural
      stimuli were compared with their responses to electrical stimulation of single
      gamma-axons supplying the same spindle. Electrical stimulation mimicked the
      natural actions of gamma-motoneurones on either the primary or the secondary
      ending, but not on both together. However, gamma-activity evoked by natural
      stimuli coupled the firing of afferents with the muscle at constant length, and
      also when it was stretched. Analysis showed that the timing and tightness of this
      coupling determined the degree of summation of excitatory postsynaptic potentials
      (EPSPs) evoked by each afferent in alpha-motoneurones and interneurones contacted
      by terminals of both endings, and thus the degree of facilitation of reflex
      actions of group II afferents.

PMID- 12181299
TI  - Distribution of the forces produced by motor unit activity in the human flexor
      digitorum profundus.
AB  - In humans, the flexor digitorum profundus (FDP), which is a multi-tendoned
      muscle, produces forces that flex the four distal interphalangeal joints of the
      fingers. We determined whether the force associated with activity in a single
      motor unit in the FDP was confined to a single finger or distributed to more than
      one finger during a natural grasp. The discharge of single low-threshold motor
      units (n = 69) was recorded at sites across the muscle during weak voluntary
      grasping involving all fingers and spike-triggered averaging of the forces under
      each of the finger pads was used to assess the distribution pattern. Spike
      triggered averaging revealed that time-locked changes in force occurred under the
      'test' finger (that finger on which the unit principally acted) as well as under
      the 'non-test' fingers. However, for the index-, middle- and ring-finger units,
      the changes in force under non-test fingers were typically small (< 20 % of those
      under the test finger). For little-finger units, the mean changes in force under
      the adjacent ring finger were large (>50 % of those under the test finger). The
      distribution of forces by little-finger units differed significantly from that
      for each of the other three fingers. Apart from increases in force under non-test
      fingers, there was occasional unloading of adjacent fingers (22/267
      combinations), usually affecting the index finger. The increases in force under
      the test finger correlated significantly with the background force for units
      acting on the middle, ring and little fingers. During a functional grasp, the
      activity of single units in the FDP allows for a relatively selective control of
      forces at the tips of the index, middle and ring fingers, but this is limited for
      little-finger units.

PMID- 12181301
TI  - Disinhibition in the human motor cortex is enhanced by synchronous upper limb
      movements.
AB  - The phasic modulation of wrist flexor corticomotor disinhibition has previously
      been demonstrated during the flexion phase of rhythmical passive flexion
      extension of the human wrist. Here we ask if rhythmical bimanual flexion
      extension movements of the wrists of neurologically intact subjects, modulate
      inhibitory activity in the motor cortex. In the first experiment intracortical
      inhibition was assessed when one wrist was passively flexed and extended on its
      own, with the addition of the opposite limb voluntarily moving synchronously in a
      mirror symmetric pattern, and also in a near-symmetric asynchronous pattern. Two
      subsequent experiments investigated firstly the modulation of spinal reflex
      pathway activity during the same three movement conditions, and secondly the
      effect of contralateral wrist movement alone on the excitability of
      corticomotoneuronal pathways to a static test limb. When the wrist flexors of
      both upper limbs were shortening simultaneously (i.e. synchronously),
      intracortical inhibition associated with flexor representations was suppressed to
      a greater extent than when the two muscles were shortening asynchronously. The
      results of the three experiments indicate that modulation of inhibitory activity
      was taking place at the cortical level. These findings may have further
      application in the study of rehabilitation procedures where the effects of
      simultaneous activation of affected and unaffected upper limbs in hemiparetic
      patients are to be investigated.

PMID- 12181302
TI  - The mechanisms of interhemispheric inhibition in the human motor cortex.
AB  - Transcranial magnetic stimulation can be used to non-invasively study inhibitory
      processes in the human motor cortex. Interhemispheric inhibition can be measured
      by applying a conditioning stimulus to the motor cortex resulting in inhibition
      of the contralateral motor cortex. Transcranial magnetic stimulation can also be
      used to demonstrate ipsilateral cortico-cortical inhibition in the motor cortex.
      At least two different ipsilateral cortico-cortical inhibitory processes have
      been identified: short interval intracortical inhibition and long interval
      intracortical inhibition. However, the relationship between interhemispheric
      inhibition and ipsilateral cortico-cortical inhibition remains unclear. This
      study examined the relationship between interhemispheric inhibition, short
      interval intracortical inhibition and long interval intracortical inhibition.
      First, the effect of test stimulus intensity on each inhibitory process was
      studied. Second, the effects of interhemispheric inhibition on short interval
      intracortical inhibition and long interval intracortical inhibition on
      interhemispheric inhibition were examined. Motor evoked potentials were recorded
      from the right first dorsal interosseous muscle in 11 right-handed healthy
      volunteers. For interhemispheric inhibition, conditioning stimuli were applied to
      the right motor cortex and test stimuli to the left motor cortex. For short
      interval intracortical inhibition and long interval intracortical inhibition,
      both conditioning stimuli and test stimuli were applied to the left motor cortex.
      With increasing test stimulus intensities, long interval intracortical inhibition
      and interhemispheric inhibition decreased, while short interval intracortical
      inhibition increased. Moreover, short interval intracortical inhibition was
      significantly reduced in the presence of interhemispheric inhibition.
      Interhemispheric inhibition was significantly reduced in the presence of long
      interval intracortical inhibition when matched for test motor evoked potential
      amplitude but the difference was not significant when matched for test pulse
      intensity. These findings suggest that both interhemispheric inhibition and long
      interval intracortical inhibition are predominately mediated by low threshold
      cortical neurons and may share common inhibitory mechanisms. In contrast, the
      mechanisms mediating short interval intracortical inhibition are probably
      different from those mediating long interval intracortical inhibition and
      interhemispheric inhibition although these systems appear to interact.

PMID- 12181300
TI  - Molecular adaptations of neuromuscular disease-associated proteins in response to
      eccentric exercise in human skeletal muscle.
AB  - The molecular events by which eccentric muscle contractions induce muscle damage
      and remodelling remain largely unknown. We assessed whether eccentric exercise
      modulates the expression of proteinases (calpains 1, 2 and 3, proteasome,
      cathepsin B+L), muscle structural proteins (alpha-sarcoglycan and desmin), and
      the expression of the heat shock proteins Hsp27 and alphaB-crystallin. Vastus
      lateralis muscle biopsies from twelve healthy male volunteers were obtained
      before, immediately after, and 1 and 14 days after a 30 min downhill treadmill
      running exercise. Eccentric exercise induced muscle damage as evidenced by the
      analysis of muscle pain and weakness, creatine kinase serum activity,
      myoglobinaemia and ultrastructural analysis of muscle biopsies. The calpain 3
      mRNA level was decreased immediately after exercise whereas calpain 2 mRNA level
      was increased at day 1. Both mRNA levels returned to control values by day 14. By
      contrast, cathepsin B+L and proteasome enzyme activities were increased at day
      14. The alpha-sarcoglycan protein level was decreased immediately after exercise
      and at day 1, whereas the desmin level peaked at day 14. alphaB-crystallin and
      Hsp27 protein levels were increased at days 1 and 14. Our results suggest that
      the differential expression of calpain 2 and 3 mRNA levels may be important in
      the process of exercise-induced muscle damage, whereas expression of alpha
      sarcoglycan, desmin, alphaB-crystallin and Hsp27 may be essentially involved in
      the subsequent remodelling of myofibrillar structure. This remodelling response
      may limit the extent of muscle damage upon a subsequent mechanical stress.

PMID- 12181303
TI  - Xanthine oxidase, but not neutrophils, contributes to activation of cardiac
      sympathetic afferents during myocardial ischaemia in cats.
AB  - Activation of cardiac sympathetic afferents during myocardial ischaemia causes
      angina and induces important cardiovascular reflex responses. Reactive oxygen
      species (ROS) are important chemical stimuli of cardiac afferents during and
      after ischaemia. Iron-catalysed Fenton chemistry constitutes one mechanism of
      production of hydroxyl radicals. Another potential source of these species is
      xanthine oxidase-catalysed oxidation of purines. Polymorphonuclear leukocytes
      (PMNs) also contribute to the production of ROS in some conditions. The present
      study tested the hypothesis that both xanthine oxidase-catalysed oxidation of
      purines and neutrophils provide a source of ROS sufficient to activate cardiac
      afferents during ischaemia. We recorded single-unit activity of cardiac afferents
      innervating the ventricles recorded from the left thoracic sympathetic chain (T1
      5) of anaesthetized cats to identify the afferents' responses to ischaemia. The
      role of xanthine oxidase in activation of these afferents was determined by
      infusion of oxypurinol (10 mg kg(-1), I.V.), an inhibitor of xanthine oxidase.
      The importance of neutrophils as a potential source of ROS in the activation of
      cardiac afferents during ischaemia was assessed by the infusion of a polyclonal
      antibody (3 mg ml(-1) kg(-1), I.V.) raised in rabbits immunized with cat PMNs.
      This antibody decreased the number of circulating PMNs and, to a smaller extent,
      platelets. Since previous data suggest that platelets release serotonin (5-HT),
      which activates cardiac afferents through a serotonin receptor (subtype 3,5-HT3
      receptor) mechanism, before treatment with the antibody in another group, we
      blocked 5-HT3 receptors on sensory nerve endings with tropisetron (300 microg kg(
      1), I.V.). We observed that oxypurinol significantly decreased the activity of
      cardiac afferents during myocardial ischaemia from 1.5 +/- 0.4 to 0.8 +/- 0.4
      impulses s(-1). Similarly, the polyclonal antibody significantly reduced the
      discharge frequency of ischaemically sensitive cardiac afferents from 2.5 +/- 0.7
      to 1.1 +/- 0.4 impulses s(-1). However, pre-blockade of 5-HT3 receptors
      eliminated the influence of the antibody on discharge activity of the afferents
      during ischaemia. This study demonstrates that ROS generated from the oxidation
      of purines contribute to the stimulation of ischaemically sensitive cardiac
      sympathetic afferents, whereas PMNs do not play a major role in this process.

PMID- 12181304
TI  - Mechanism of blood pressure and R-R variability: insights from ganglion blockade
      in humans.
AB  - Spontaneous blood pressure (BP) and R-R variability are used frequently as
      'windows' into cardiovascular control mechanisms. However, the origin of these
      rhythmic fluctuations is not completely understood. In this study, with ganglion
      blockade, we evaluated the role of autonomic neural activity versus other 'non
      neural' factors in the origin of BP and R-R variability in humans. Beat-to-beat
      BP, R-R interval and respiratory excursions were recorded in ten healthy subjects
      (aged 30 +/- 6 years) before and after ganglion blockade with trimethaphan. The
      spectral power of these variables was calculated in the very low (0.0078-0.05
      Hz), low (0.05-0.15 Hz) and high (0.15-0.35 Hz) frequency ranges. The
      relationship between systolic BP and R-R variability was examined by cross
      spectral analysis. After blockade, R-R variability was virtually abolished at all
      frequencies; however, respiration and high frequency BP variability remained
      unchanged. Very low and low frequency BP variability was reduced substantially by
      84 and 69 %, respectively, but still persisted. Transfer function gain between
      systolic BP and R-R interval variability decreased by 92 and 88 % at low and high
      frequencies, respectively, while the phase changed from negative to positive
      values at the high frequencies. These data suggest that under supine resting
      conditions with spontaneous breathing: (1) R-R variability at all measured
      frequencies is predominantly controlled by autonomic neural activity; (2) BP
      variability at high frequencies (> 0.15 Hz) is mediated largely, if not
      exclusively, by mechanical effects of respiration on intrathoracic pressure
      and/or cardiac filling; (3) BP variability at very low and low frequencies (<
      0.15 Hz) is probably mediated by both sympathetic nerve activity and intrinsic
      vasomotor rhythmicity; and (4) the dynamic relationship between BP and R-R
      variability as quantified by transfer function analysis is determined
      predominantly by autonomic neural activity rather than other, non-neural factors.

PMID- 12181305
TI  - Role of central command in carotid baroreflex resetting in humans during static
      exercise.
AB  - The purpose of the experiments was to examine the role of central command in the
      exercise-induced resetting of the carotid baroreflex. Eight subjects performed 30
      % maximal voluntary contraction (MVC) static knee extension and flexion with
      manipulation of central command (CC) by patellar tendon vibration (PTV). The same
      subjects also performed static knee extension and flexion exercise without PTV at
      a force development that elicited the same ratings of perceived exertion (RPE) as
      those observed during exercise with PTV in order to assess involvement of the
      exercise pressor reflex. Carotid baroreflex (CBR) function curves were modelled
      from the heart rate (HR) and mean arterial pressure (MAP) responses to rapid
      changes in neck pressure and suction during steady state static exercise. Knee
      extension exercise with PTV (decreased CC activation) reset the CBR-HR and CBR
      MAP to a lower operating pressure (P < 0.05) and knee flexion exercise with PTV
      (increased CC activation) reset the CBR-HR and CBR-MAP to a higher operating
      pressure (P < 0.05). Comparison between knee extension and flexion exercise at
      the same RPE with and without PTV found no difference in the resetting of the CBR
      HR function curves (P > 0.05) suggesting the response was determined primarily by
      CC activation. However, the CBR-MAP function curves were reset to operating
      pressures determined by both exercise pressor reflex (EPR) and central command
      activation. Thus the physiological response to exercise requires CC activation to
      reset the carotid-cardiac reflex but requires either CC or EPR to reset the
      carotid-vasomotor reflex.

PMID- 12181306
TI  - The effect of testosterone on regional blood flow in prepubertal anaesthetized
      pigs.
AB  - This work was undertaken to study the effects of testosterone on the coronary,
      mesenteric, renal and iliac circulations and to determine the mechanisms of
      action involved. In prepubertal pigs of both sexes anaesthetized with sodium
      pentobarbitone, changes in left circumflex or anterior descending coronary,
      superior mesenteric, left renal and left external iliac blood flow caused by
      intra-arterial infusion of testosterone were assessed using electromagnetic
      flowmeters. Changes in heart rate and arterial blood pressure were prevented by
      atrial pacing and by connecting the arterial system to a pressurized reservoir
      containing Ringer solution. In 12 pigs, intra-arterial infusion of testosterone
      for 5 min to achieve a stable intra-arterial concentration of 1 microg l(-1)
      increased coronary, mesenteric, renal and iliac blood flow without affecting the
      maximum rate of change of left ventricular systolic pressure (left ventricular
      dP/dt(max)) and filling pressures of the heart. In a further five pigs, a
      concentration-response curve was obtained by graded increases in the intra
      arterial concentration of the hormone between 0.125 and 8 microg l(-1). The
      mechanisms of these responses were studied in the 12 pigs by repeating the
      experiment after haemodynamic variables had returned to the control values before
      infusions. In six pigs, blockade of muscarinic cholinoceptors and adrenoceptors
      with atropine, propranolol and phentolamine did not affect the responses caused
      by intra-arterial infusion of testosterone performed to achieve a stable intra
      arterial concentration of 1 microg l(-1). In the same pigs and in the remaining
      six pigs, the increases in coronary, mesenteric, renal and iliac blood flow
      caused by intra-arterial infusion of testosterone performed to achieve a stable
      intra-arterial concentration of 1 microg l(-1) were prevented by intra-arterial
      injection of N(omega)-nitro-L-arginine methyl ester. The present study shows that
      intra-arterial infusion of testosterone dilated coronary, mesenteric, renal and
      iliac circulations. The mechanism of this response involved the release of nitric
      oxide.

PMID- 12181307
TI  - Interleukin-6 production in human subcutaneous abdominal adipose tissue: the
      effect of exercise.
AB  - The interleukin-6 (IL-6) output from subcutaneous, abdominal adipose tissue was
      studied in nine healthy subjects before, during and for 3 h after 1 h two-legged
      bicycle exercise at 60 % maximal oxygen consumption. Seven subjects were studied
      in control experiments without exercise. The adipose tissue IL-6 output was
      measured by direct Fick technique. An artery and a subcutaneous vein on the
      anterior abdominal wall were catheterized. Adipose tissue blood flow was measured
      using the 133Xe-washout method. In both studies there was a significant IL-6
      output in the basal state and no significant change was observed during exercise.
      Post-exercise the IL-6 output began to increase after 30 min. Three hours post
      exercise it was 58.6 +/- 22.2 pg (100 g)(-1) min(-1). In the control experiments
      the IL-6 output also increased, but it only reached a level of 3.5 +/- 0.8 pg
      (100 g)(-1) min(-1). The temporal profile of the post-exercise change in the IL-6
      output closely resembles the changes in the outputs of glycerol and fatty acids,
      which we have described previously in the same adipose tissue depot. The
      difference is that it begins to increase ~30 min before the glycerol and fatty
      acid outputs begin to increase. Thus, we suggest that the enhanced IL-6
      production post-exercise in abdominal, subcutaneous adipose tissue may act
      locally via autocrine/paracrine mechanisms influencing lipolysis and fatty acid
      mobilization rate from this lipid depot.

PMID- 12181308
TI  - Metabolic effects of interleukin-6 in human splanchnic and adipose tissue.
AB  - Interleukin-6 (IL-6) was infused intravenously for 2.5 h in seven healthy human
      volunteers at a dose giving rise to a circulating IL-6 concentration of
      approximately 35 ng l(-1). The metabolic effects of this infusion were studied in
      subcutaneous adipose tissue on the anterior abdominal wall and in the splanchnic
      tissues by the Fick principle after catheterizations of an artery, a subcutaneous
      vein draining adipose tissue, and a hepatic vein, and measurements of regional
      adipose tissue and splanchnic blood flows. In control studies without IL-6
      infusion subcutaneous adipose tissue metabolism was studied by the same technique
      in eight healthy subjects. The net release of glycerol and fatty acids from the
      subcutaneous abdominal adipose tissue remained constant in the control
      experiment. IL-6 infusion gave rise to increase in net glycerol release in
      subcutaneous adipose tissue while the net release of fatty acids did not change
      significantly. In the splanchnic region IL-6 elicited a pronounced
      vasodilatation, and the uptake of fatty acids and the gluconeogenic precursors
      glycerol and lactate increased significantly. The splanchnic net output of
      glucose and triacylglycerol did not change during the IL-6 infusion. It is
      concluded that IL-6 elicits lipolytic effects in human adipose tissue in vivo,
      and that IL-6 also has effects on the splanchnic lipid and carbohydrate
      metabolism.

PMID- 12181309
TI  - Prenatal hypoxia impairs circadian synchronisation and response of the biological
      clock to light in adult rats.
AB  - The aim of this study was to test the hypothesis that prenatal hypoxia in rats
      might lead to consistent changes in the entrainment of the circadian clock by
      light. Pregnant female rats were placed in a chamber provided with hypoxic gas
      (10 % O2--90 % N2) at gestational day 5 and returned to normoxia before delivery.
      Once adult, rats born to hypoxic mothers had significant alterations in their
      circadian rhythm of locomotor activity (recorded in freely accessible running
      wheels). Under a regular 12/12 light/dark (LD) cycle, they showed a phase advance
      of their rhythm of activity (mean phase advance of 87 min) and were less active
      than control rats. After an abrupt 6 h phase delay in the LD cycle, rats from the
      prenatal hypoxic group (PNH) took significantly more time to resynchronise to the
      new LD cycle compared to controls (+53 %; 6.0 +/- 1.5 vs. 9.2 +/- 0.5 days
      respectively). Under constant darkness, PNH and control rats had a similar period
      of activity (24.27 +/- 0.20 vs. 24.40 +/- 0.13) but the response of PNH rats to a
      light pulse in the early subjective night was less marked than that of control
      rats (101 +/- 9 vs. 158 +/- 13 min). When submitted to acute restraint stress,
      PNH rats had a prolonged secretion of corticosterone compared to controls. These
      results indicate that prenatal hypoxia is a factor that has long lasting
      consequences for the functional output of the biological clock and the hormonal
      response to stress.

PMID- 12181310
TI  - 1,25-Dihydroxyvitamin D down-regulates cell membrane growth- and nuclear growth
      promoting signals by the epidermal growth factor receptor.
AB  - 1,25(OH)(2)D(3) antiproliferative properties are widely known. However, the
      molecular bases of these properties are only partially elucidated. Since
      1,25(OH)(2)D(3) effectively arrests growth in many tumors and hyperplastic
      tissues whose growth is driven by co-expression of EGFR and its ligand TGF-alpha,
      it was hypothesized that 1,25(OH)(2)D(3) could affect the TGF-alpha/EGFR
      autocrine growth loop. This study examined 1,25(OH)(2)D(3) regulation of EGFR
      growth signals, using human epidermoid A431 cells, in which the overexpression of
      EGFR and TGF-alpha constitute the major autocrine mitogenic signal.
      1,25(OH)(2)D(3) inhibited autocrine and EGF-induced A431 cell proliferation.
      Furthermore, 1,25(OH)(2)D(3) changed the cellular localization of both TGF-alpha
      and EGFR and inhibited ligand-dependent phosphorylation of EGFR and ERK1/2. In
      addition, 1,25(OH)(2)D(3) impaired autocrine and EGF-induced nuclear
      translocation of activated EGFR and, consequently, its binding to AT-rich DNA
      sequences and transcriptional activation of the cyclin D1 promoter. These results
      demonstrate that 1,25(OH)(2)D(3) alters EGFR membrane trafficking and down
      regulates EGFR growth signaling.

PMID- 12181311
TI  - Definition of an inhibitory juxtamembrane WW-like domain in the platelet-derived
      growth factor beta receptor.
AB  - A variety of tumors contain activating mutations in the cytoplasmic juxtamembrane
      domain of the type III family of receptor-tyrosine kinases, and some constructed
      mutations in this domain induce ligand-independent receptor activation. To
      explore the role of this domain in regulation of receptor activity, we subjected
      the juxtamembrane domain of the murine platelet-derived growth factor (PDGF) beta
      receptor to alanine-scanning mutagenesis. The mutant receptors were expressed in
      Ba/F3 cells and tested for constitutive tyrosine phosphorylation, association
      with phosphatidylinositol 3'-kinase, and their ability to induce cell survival
      and proliferation in the absence of interleukin-3. The mutant receptors
      accumulated to similar levels and appeared to undergo a normal PDGF-induced
      increase in tyrosine phosphorylation. Alanine substitutions at numerous positions
      located throughout the juxtamembrane domain caused constitutive receptor
      activation, as did an alanine insertion in the membrane-proximal segment of the
      juxtamembrane domain and a six-amino acid deletion in the center of the domain.
      It is possible to model the PDGF receptor juxtamembrane domain as a short alpha
      helix followed by a three-stranded beta-sheet very similar to the known
      structures of WW domains. Strikingly, the activating mutations clustered in the
      central portions of the first and second beta strands and along one face of the
      beta-sheet, whereas the loops connecting the strands were largely devoid of
      mutationally sensitive positions. These findings provide strong support for the
      model that the activating mutations in the juxtamembrane region stimulate
      receptor activity by disrupting an inhibitory WW-like domain.

PMID- 12181312
TI  - The androgen receptor interacts with multiple regions of the large subunit of
      general transcription factor TFIIF.
AB  - The androgen receptor (AR) is a ligand-activated transcription factor that
      regulates genes important for male development and reproductive function. The
      main determinants for the transactivation function lie within the structurally
      distinct amino-terminal domain. Previously we identified an interaction between
      the AR-transactivation domain (amino acids 142-485) and the general transcription
      factor TFIIF (McEwan, I. J., and Gustafsson, J.-A. (1997) Proc. Natl. Acad. Sci.
      U. S. A. 94, 8485-8490). We have now mapped the binding sites for the AR
      transactivation domain within the RAP74 subunit of TFIIF. Both the amino-terminal
      136 amino acids and the carboxyl-terminal 155 amino acids of RAP74 interacted
      with the AR-transactivation domain and were able to rescue basal transcription
      after squelching by the AR polypeptide. Competition experiments demonstrated that
      the AR could interact with the holo-TFIIF protein and that the carboxyl terminus
      of RAP74 represented the principal receptor-binding site. Point mutations within
      AR-transactivation domain distinguished the binding sites for RAP74 and the p160
      coactivator SRC-1a and identified a single copy of a six amino acid repeat motif
      as being important for RAP74 binding. These data indicate that the AR
      transactivation domain can potentially make multiple protein-protein interactions
      with coactivators and components of the general transcriptional machinery in
      order to regulate target gene expression.

PMID- 12181313
TI  - Telomere-binding protein TRF2 binds to and stimulates the Werner and Bloom
      syndrome helicases.
AB  - Werner syndrome is a human premature aging disorder displaying cellular defects
      associated with telomere maintenance including genomic instability, premature
      senescence, and accelerated telomere erosion. The yeast homologue of the Werner
      protein (WRN), Sgs1, is required for recombination-mediated lengthening of
      telomeres in telomerase-deficient cells. In human cells, we report that WRN co
      localizes and physically interacts with the critical telomere maintenance protein
      TRF2. This interaction is mediated by the RecQ conserved C-terminal region of
      WRN. In vitro, TRF2 demonstrates high affinity for WRN and for another RecQ
      family member, the Bloom syndrome protein (BLM). TRF2 interaction with either WRN
      or BLM results in a notable stimulation of their helicase activities.
      Furthermore, the WRN and BLM helicases, partnered with replication protein A,
      actively unwind long telomeric duplex regions that are pre-bound by TRF2. These
      results suggest that TRF2 functions with WRN, and possibly BLM, in a common
      pathway at telomeric ends.

PMID- 12181314
TI  - Active site in RrmJ, a heat shock-induced methyltransferase.
AB  - The heat shock protein RrmJ (FtsJ), highly conserved from eubacteria to eukarya,
      is responsible for the 2'-O-ribose methylation of the universally conserved base
      U2552 in the A-loop of the 23 S rRNA. Absence of this methylation, which occurs
      late in the maturation process of the ribosome, appears to cause the
      destabilization and premature dissociation of the 50 S ribosomal subunit. To
      understand the mechanism of 2'-O-ribose methyltransfer reactions, we
      characterized the enzymatic parameters of RrmJ and conducted site-specific
      mutagenesis of RrmJ. A structure based sequence alignment with VP39, a
      structurally related 2'-O-methyltransferase from vaccinia virus, guided our
      mutagenesis studies. We analyzed the function of our RrmJ mutants in vivo and
      characterized the methyltransfer reaction of the purified proteins in vitro. The
      active site of RrmJ appears to be formed by a catalytic triad consisting of two
      lysine residues, Lys-38 and Lys-164, and the negatively charged residue Asp-124.
      Another highly conserved residue, Glu-199, that is present in the active site of
      RrmJ and VP39 appears to play only a minor role in the methyltransfer reaction in
      vivo. Based on these results, a reaction mechanism for the methyltransfer
      activity of RrmJ is proposed.

PMID- 12181315
TI  - Structural and dynamic features of Alzheimer's Abeta peptide in amyloid fibrils
      studied by site-directed spin labeling.
AB  - Electron paramagnetic resonance spectroscopy analysis of 19 spin-labeled
      derivatives of the Alzheimer's amyloid beta (Abeta) peptide was used to reveal
      structural features of amyloid fibril formation. In the fibril, extensive regions
      of the peptide show an in-register, parallel arrangement. Based on the parallel
      arrangement and side chain mobility analysis we find the amyloid structure to be
      mostly ordered and specific, but we also identify more dynamic regions (N and C
      termini) and likely turn or bend regions (around residues 23-26). Despite their
      different aggregation properties and roles in disease, the two peptides, Abeta40
      and Abeta42, homogeneously co-mix in amyloid fibrils suggesting that they possess
      the same structural architecture.

PMID- 12181316
TI  - A polyamine analogue prevents acute pancreatitis and restores early liver
      regeneration in transgenic rats with activated polyamine catabolism.
AB  - We recently generated a transgenic rat model for acute pancreatitis, which was
      apparently caused by a massive depletion of pancreatic polyamines spermidine and
      spermine due to inducible activation of their catabolism (Alhonen, L., Parkkinen,
      J. J., Keinanen, T., Sinervirta, R., Herzig, K. H., and Janne, J. (2000) Proc.
      Natl. Acad. Sci. U. S. A. 97, 8290-8295). When subjected to partial hepatectomy,
      these animals showed striking activation of polyamine catabolism at 24 h
      postoperatively with a profound decrease in hepatic spermidine and spermine pools
      and failure to initiate liver regeneration. Here we show that pancreatitis in
      this model could be totally prevented, as judged by histopathology and plasma
      alpha-amylase activity, by administration of 1-methylspermidine, a metabolically
      stable analogue of spermidine. Similarly, the analogue, given prior to partial
      hepatectomy, restored early liver regeneration in the transgenic rats, as
      indicated by a dramatic increase in the number of proliferating cell nuclear
      antigen-positive hepatocytes from about 1% to more than 40% in response to the
      drug. The present results suggest that the extremely high concentration of
      spermidine in the pancreas, in fact the highest in the mammalian body, may have a
      critical role in maintaining organ integrity. The failure to initiate liver
      regeneration in the absence of sufficient hepatic polyamine pools similarly
      indicates that polyamines are required for proper commencement of the
      regenerative process.

PMID- 12181317
TI  - Involvement of calcium-independent phospholipase A2 in hydrogen peroxide-induced
      accumulation of free fatty acids in human U937 cells.
AB  - Previous studies have demonstrated that U937 cells are able to mobilize
      arachidonic acid (AA) and synthesize prostaglandins in response to receptor
      directed and soluble stimuli by a mechanism that involves the activation of Group
      IV cytosolic phospholipase A(2)alpha. In this paper we show that these cells also
      mobilize AA in response to an oxidative stress induced by H(2)O(2) through a
      mechanism that appears not to be mediated by cytosolic phospholipase A(2)alpha
      but by the calcium-independent Group VI phospholipase A(2) (iPLA(2)). This is
      supported by the following lines of evidence: (i) the response is essentially
      calcium-independent, (ii) it is inhibited by bromoenol lactone, and (iii) it is
      inhibited by an iPLA(2) antisense oligonucleotide. Enzyme assays conducted under
      a variety of conditions reveal that the specific activity of the iPLA(2) does not
      change as a result of H(2)O(2) exposure, which argues against the activation of a
      specific signaling cascade ending in the iPLA(2). Rather, the oxidant acts to
      perturb membrane homeostasis in a way that the enzyme
      susceptibility/accessibility to its substrate increases, and this results in
      altered fatty acid release. In support of this view, not only AA, but also other
      fatty acids, were found to be liberated in an iPLA(2)-dependent manner in the
      H(2)O(2)-treated cells. Collectively, these studies underscore the importance of
      the iPLA(2) in modulating homeostatic fatty acid deacylation reactions and
      document a potentially important route under pathophysiological conditions for
      increasing free fatty acid levels during oxidative stress.

PMID- 12181318
TI  - Ser(214) is crucial for substrate binding to serine proteases.
AB  - Highly conserved amino acids that form crucial structural elements of the
      catalytic apparatus can be used to account for the evolutionary history of serine
      proteases and the cascades into which they are organized. One such evolutionary
      marker in chymotrypsin-like proteases is Ser(214), located adjacent to the active
      site and forming part of the primary specificity pocket. Here we report the
      mutation of Ser(214) in thrombin to Ala, Thr, Cys, Asp, Glu, and Lys. None of the
      mutants seriously compromises active site catalytic function as measured by the
      kinetic parameter k(cat). However, the least conservative mutations result in
      large increases in K(m) because of lower rates of substrate diffusion into the
      active site. Therefore, the role of Ser(214) is to promote the productive
      formation of the enzyme-substrate complex. The S214C mutant is catalytically
      inactive, which suggests that during evolution the TCN-->AGY codon transitions
      for Ser(214) occurred through Thr intermediates.

PMID- 12181319
TI  - Peroxisome proliferator-activated receptor coactivator-1alpha (PGC-1alpha)
      coactivates the cardiac-enriched nuclear receptors estrogen-related receptor
      alpha and -gamma. Identification of novel leucine-rich interaction motif within
      PGC-1alpha.
AB  - The transcriptional coactivator PPARgamma coactivator-1alpha (PGC-1alpha) has
      been characterized as a broad regulator of cellular energy metabolism. Although
      PGC-1alpha functions through many transcription factors, the PGC-1alpha partners
      identified to date are unlikely to account for all of its biologic actions. The
      orphan nuclear receptor estrogen-related receptor alpha (ERRalpha) was identified
      in a yeast two-hybrid screen of a cardiac cDNA library as a novel PGC-1alpha
      binding protein. ERRalpha was implicated previously in regulating the gene
      encoding medium-chain acyl-CoA dehydrogenase (MCAD), which catalyzes the initial
      step in mitochondrial fatty acid oxidation. The cardiac perinatal expression
      pattern of ERRalpha paralleled that of PGC-1alpha and MCAD. Adenoviral-mediated
      ERRalpha overexpression in primary neonatal cardiac mycoytes induced endogenous
      MCAD expression. Furthermore, PGC-1alpha enhanced the transactivation of reporter
      plasmids containing an estrogen response element or the MCAD gene promoter by
      ERRalpha and the related isoform ERRgamma. In vitro binding experiments
      demonstrated that ERRalpha interacts with PGC-1alpha via its activation function
      2 homology region. Mutagenesis studies revealed that the LXXLL motif at amino
      acid position 142-146 of PGC-1alpha (L2), necessary for PGC-1alpha interactions
      with other nuclear receptors, is not required for the PGC-1alpha.ERRalpha
      interaction. Rather, ERRalpha binds PGC-1alpha primarily through a Leu-rich motif
      at amino acids 209-213 (Leu-3) and utilizes additional LXXLL-containing domains
      as accessory binding sites. Thus, the PGC-1alpha.ERRalpha interaction is distinct
      from that of other nuclear receptor PGC-1alpha partners, including PPARalpha,
      hepatocyte nuclear factor-4alpha, and estrogen receptor alpha. These results
      identify ERRalpha and ERRgamma as novel PGC-1alpha interacting proteins,
      implicate ERR isoforms in the regulation of mitochondrial energy metabolism, and
      suggest a potential mechanism whereby PGC-1alpha selectively binds transcription
      factor partners.

PMID- 12181320
TI  - Substrate conformational restriction and CD45-catalyzed dephosphorylation of tail
      tyrosine-phosphorylated Src protein.
AB  - Hydrolysis of the tail phosphotyrosine in Src family members is catalyzed by the
      protein-tyrosine phosphatase CD45, activating Src family-related signaling
      pathways. Using purified recombinant phospho-Src (P-Src) (amino acid residues 83
      533) and purified recombinant CD45 catalytic (cytoplasmic) domain (amino acid
      residues 565-1268), we have analyzed the kinetic behavior of dephosphorylation. A
      time course of phosphatase activity showed the presence of a burst phase. By
      varying the concentration of P-Src, it was shown that the amplitude of this burst
      phase increased linearly with respect to P-Src concentration. Approximately 2% of
      P-Src was shown to be rapidly dephosphorylated followed by a slower linear phase.
      A P-Src protein substrate containing a functional point mutation in the Src
      homology domain 2 (SH2) led to more rapid dephosphorylation catalyzed by CD45,
      and this reaction showed only a single linear kinetic phase. These results were
      interpreted in terms of a model in which P-Src exists in a relatively slow
      dynamic equilibrium between "closed" and "open" conformational forms. Combined
      mutations in the SH2 and SH3 domain or the addition of an SH3 domain ligand
      peptide enhanced the accessibility of P-Src to CD45 by biasing P-Src to a more
      open form. Consistent with this model, a phosphotyrosine peptide that behaved as
      an SH2 domain binding ligand showed approximately 100-fold greater affinity for
      unphosphorylated Src versus P-Src. Surprisingly, P-Src possessing combined SH3
      and SH2 functional inactivating point mutations was dephosphorylated by CD45 more
      slowly compared with P-Src completely lacking SH3 and SH2 domains. Additional
      data suggest that the SH3 and SH2 domains can inhibit accessibility of the P-Src
      tail to CD45 by interactions other than direct phosphotyrosine binding by the SH2
      domain. Taken together, these results suggest how activation of Src family member
      signaling pathways by CD45 may be influenced by the presence or absence of ligand
      interactions remote from the tail.

PMID- 12181321
TI  - DEAD box RhlB RNA helicase physically associates with exoribonuclease PNPase to
      degrade double-stranded RNA independent of the degradosome-assembling region of
      RNase E.
AB  - The Escherichia coli RNA degradosome is a multicomponent ribonucleolytic complex
      consisting of three major proteins that assemble on a scaffold provided by the C
      terminal region of the endonuclease, RNase E. Using an E. coli two-hybrid system,
      together with BIAcore apparatus, we investigated the ability of three proteins,
      polynucleotide phosphorylase (PNPase), RhlB RNA helicase, and enolase, a
      glycolytic protein, to interact physically and functionally independently of
      RNase E. Here we report that Rh1B can physically bind to PNPase, both in vitro
      and in vivo, and can also form homodimers with itself. However, binding of RhlB
      or PNPase to enolase was not detected under the same conditions. BIAcore analysis
      revealed real-time, direct binding for bimolecular interactions between Rh1B
      units and for the RhlB interaction with PNPase. Furthermore, in the absence of
      RNase E, purified RhlB can carry out ATP-dependent unwinding of double-stranded
      RNA and consequently modulate degradation of double-stranded RNA together with
      the exonuclease activity of PNPase. These results provide evidence for the first
      time that both functional and physical interactions of individual degradosome
      protein components can occur in the absence of RNase E and raise the prospect
      that the RNase E-independent complexes of RhlB RNA helicase and PNPase, detected
      in vivo, may constitute mini-machines that assist in the degradation of duplex
      RNA in structures physically distinct from multicomponent RNA degradosomes.

PMID- 12181322
TI  - mRNA decay is rapidly induced after spore germination of Saccharomyces
      cerevisiae.
AB  - Spores from the yeast Saccharomyces cerevisiae can germinate and resume their
      vegetative growth when placed in favorable conditions. Biochemical studies on
      germination have been limited by the difficulty of obtaining a pure population of
      spores germinating synchronously. Here, we report that spores can be purified and
      sorted according to their size by centrifugal elutriation and that these spores
      are able to germinate synchronously. Synchronizing their development has allowed
      reevaluating certain parameters of germination, and we demonstrate that both
      transcription and translation are induced very rapidly after germination
      induction. Spores contain mRNAs that are stable for several months in spores kept
      at 4 degrees C. Germination induction leads to very rapid degradation of these
      mRNAs, thus providing a simple model to study induction of mRNA decay in
      eukaryotes. mRNAs from the spore are polyadenylated, capped, and cosediment on
      sucrose gradients with ribosomes and polysomes and with components of the mRNA
      degradation machinery. The presence of polysomes in the spores led us to evaluate
      the activity of the translation apparatus in these cells. We present evidence
      that there is ongoing transcription and translation in nongerminating yeast
      spores incubated in water at 30 degrees C, suggesting that these activities could
      play a role in spore long term survival.

PMID- 12181323
TI  - Negative regulation of Epstein-Barr virus latent membrane protein 1-mediated
      functions by the bone morphogenetic protein receptor IA-binding protein, BRAM1.
AB  - The latent membrane protein 1 (LMP1) of Epstein-Barr virus causes cellular
      transformation and activates several intracellular signals, including NF-kappaB
      and c-Jun N-terminal kinase. Using yeast two-hybrid screening with the LMP1 C
      terminal sequence as bait, we demonstrate that BRAM1 (bone morphogenetic protein
      receptor-associated molecule 1) is an LMP1-interacting protein. BRAM1 associates
      with LMP1, both in vitro and in vivo, as revealed by confocal microscopy,
      glutathione S-transferase pull-down, and co-immunoprecipitation assays. This
      association mainly involves the C-terminal half of BRAM1 comprising the MYND
      domain and the CTAR2 region of LMP1, which is critical in LMP1-mediated signaling
      pathways. We show that BRAM1 interferes with LMP1-mediated NF-kappaB activation
      but not the JNK signaling pathway. Because the CTAR2 region interacts with the
      tumor necrosis factor (TNF-alpha receptor-associated death domain protein, it is
      interesting to find that BRAM1 also interferes with NF-kappaB activation mediated
      by TNF-alpha. BRAM1 interferes LMP1-mediated and TNF-alpha-induced NF-kappaB
      activation by targeting IkappaBalpha molecules. Moreover, BRAM1 inhibits the
      resistance of LMP1-expressing cells to TNF-alpha-induced cytotoxicity. We
      therefore propose that the BRAM1 molecule associates with LMP1 and functions as a
      negative regulator of LMP1-mediated biological functions.

PMID- 12181325
TI  - The role of apolipoprotein A-I helix 10 in apolipoprotein-mediated cholesterol
      efflux via the ATP-binding cassette transporter ABCA1.
AB  - Recent studies of Tangier disease have shown that the ATP-binding cassette
      transporter A1 (ABCA1)/apolipoprotein A-I (apoA-I) interaction is critical for
      high density lipoprotein particle formation, apoA-I integrity, and proper reverse
      cholesterol transport. However, the specifics of this interaction are unknown. It
      has been suggested that amphipathic helices of apoA-I bind to a lipid domain
      created by the ABCA1 transporter. Alternatively, apoA-I may bind directly to
      ABCA1 itself. To better understand this interaction, we created several
      truncation mutants of apoA-I and then followed up with more specific point
      mutants and helix translocation mutants to identify and characterize the
      locations of apoA-I required for ABCA1-mediated cholesterol efflux. We found that
      deletion of residues 221-243 (helix 10) abolished ABCA1-mediated cholesterol
      efflux from cultured RAW mouse macrophages treated with 8-bromo-cAMP. Point
      mutations in helix 10 that affected the helical charge distribution reduced ABCA1
      mediated cholesterol efflux versus the wild type. We noted a strong positive
      correlation between cholesterol efflux and the lipid binding characteristics of
      apoA-I when mutations were made in helix 10. However, there was no such
      correlation for helix translocations in other areas of the protein as long as
      helix 10 remained intact at the C terminus. From these observations, we propose
      an alternative model for apolipoprotein-mediated efflux.

PMID- 12181326
TI  - Characterization of a Schizosaccharomyces pombe strain deleted for a sequence
      homologue of the human damaged DNA binding 1 (DDB1) gene.
AB  - Human damaged DNA-binding protein (DDB) is a heterodimer of p48/DDB2 and
      p127/DDB1 subunits. Mutations in DDB2 are responsible for Xeroderma Pigmentosum
      group E, but no mutants of mammalian DDB1 have been described. To study DDB1, the
      Schizosaccharomyces pombe DDB1 sequence homologue (ddb1(+)) was cloned, and a
      ddb1 deletion strain was constructed. The gene is not essential; however, mutant
      cells showed a 37% impairment in colony-forming ability, an elongated phenotype,
      and abnormal nuclei. The ddb1Delta strain was sensitive to UV irradiation, X
      rays, methylmethane sulfonate, and thiabendazole, and these sensitivities were
      compared with those of the well characterized rad13Delta, rhp51Delta, and
      cds1Delta mutant strains. Ddb1p showed nuclear and nucleolar localization, and
      the aberrant nuclear structures observed in the ddb1Delta strain suggest a role
      for Ddb1p in chromosome segregation.

PMID- 12181324
TI  - Sequence determinants in hypoxia-inducible factor-1alpha for hydroxylation by the
      prolyl hydroxylases PHD1, PHD2, and PHD3.
AB  - Hypoxia-inducible factor (HIF) is a heterodimeric transcription factor induced by
      hypoxia. Under normoxic conditions, site-specific proline hydroxylation of the
      alpha subunits of HIF allows recognition by the von Hippel-Lindau tumor
      suppressor protein (VHL), a component of an E3 ubiquitin ligase complex that
      targets these subunits for degradation by the ubiquitin-proteasome pathway. Under
      hypoxic conditions, this hydroxylation is inhibited, allowing the alpha subunits
      of HIF to escape VHL-mediated degradation. Three enzymes, prolyl hydroxylase
      domain-containing proteins 1, 2, and 3 (PHD1, -2, and -3; also known as HIF
      prolyl hydroxylase 3, 2, and 1, respectively), have recently been identified that
      catalyze proline hydroxylation of HIF alpha subunits. These enzymes hydroxylate
      specific prolines in HIF alpha subunits in the context of a strongly conserved
      LXXLAP sequence motif (where X indicates any amino acid and P indicates the
      hydroxylacceptor proline). We report here that PHD2 has the highest specific
      activity toward the primary hydroxylation site of HIF-1alpha. Furthermore, and
      unexpectedly, mutations can be tolerated at the -5, -2, and -1 positions
      (relative to proline) of the LXXLAP motif. Thus, these results provide evidence
      that the only obligatory residue for proline hydroxylation in HIF-1alpha is the
      hydroxylacceptor proline itself.

PMID- 12181327
TI  - A dominant-negative mutant of human DNA helicase B blocks the onset of
      chromosomal DNA replication.
AB  - A cDNA encoding a human ortholog of mouse DNA helicase B, which may play a role
      in DNA replication, has been cloned and expressed as a recombinant protein. The
      predicted human DNA helicase B (HDHB) protein contains conserved helicase motifs
      (superfamily 1) that are strikingly similar to those of bacterial recD and T4 dda
      proteins. The HDHB gene is expressed at low levels in liver, spleen, kidney, and
      brain and at higher levels in testis and thymus. Purified recombinant HDHB
      hydrolyzed ATP and dATP in the presence of single-stranded DNA, displayed robust
      5'-3' DNA helicase activity, and interacted physically and functionally with DNA
      polymerase alpha-primase. HDHB proteins with mutations in the Walker A or B motif
      lacked ATPase and helicase activity but retained the ability to interact with DNA
      polymerase alpha-primase, suggesting that the mutants might be dominant over
      endogenous HDHB in human cells. When purified HDHB protein was microinjected into
      the nucleus of cells in early G(1), the mutant proteins inhibited DNA synthesis,
      whereas the wild type protein had no effect. Injection of wild type or mutant
      protein into cells at G(1)/S did not prevent DNA synthesis. The results suggest
      that HDHB function is required for S phase entry.

PMID- 12181328
TI  - A research journey with ATP synthase.

PMID- 12181329
TI  - Casein kinase I regulates membrane binding by ARF GAP1.
AB  - ARF GAP1, a 415-amino acid GTPase activating protein (GAP) for ADP-ribosylation
      factor (ARF) contains an amino-terminal 115-amino acid catalytic domain and no
      other recognizable features. Amino acids 203-334 of ARF GAP1 were sufficient to
      target a GFP-fusion protein to Golgi membranes in vivo. When overexpressed in COS
      1 cells, this protein domain inhibited protein transport between the ER and Golgi
      and, in vitro, competed with the full-length ARF GAP1 for binding to membranes.
      Membrane binding by ARF GAP1 in vitro was increased by a factor in cytosol and
      this increase was inhibited by IC261, an inhibitor selective for casein kinase
      Idelta (CKIdelta), or when cytosol was treated with antibody to CKIdelta. The
      noncatalytic domain of ARF GAP1 was phosphorylated both in vivo and in vitro by
      CKI. IC261 blocked membrane binding by ARF GAP1 in vivo and inhibited protein
      transport in the early secretory pathway. Overexpression of a catalytically
      inactive CKIdelta also inhibited the binding of ARF GAP1 to membranes and
      interfered with protein transport. Thus, a CKI isoform is required for protein
      traffic through the early secretory pathway and can modulate the amount of ARF
      GAP1 that can bind to membranes.

PMID- 12181330
TI  - Crp79p, like Mex67p, is an auxiliary mRNA export factor in Schizosaccharomyces
      pombe.
AB  - The export of mRNA from the nucleus to the cytoplasm involves interactions of
      proteins with mRNA and the nuclear pore complex. We isolated Crp79p, a novel mRNA
      export factor from the same synthetic lethal screen that led to the
      identification of spMex67p in Schizosaccharomyces pombe. Crp79p is a 710-amino
      acid-long protein that contains three RNA recognition motif domains in tandem and
      a distinct C-terminus. Fused to green fluorescent protein (GFP), Crp79p localizes
      to the cytoplasm. Like Mex67p, Crp79-GFP binds poly(A)(+) RNA in vivo, shuttles
      between the nucleus and the cytoplasm, and contains a nuclear export activity at
      the C-terminus that is Crm1p-independent. All of these properties are essential
      for Crp79p to promote mRNA export. Crp79p import into the nucleus depends on the
      Ran system. A domain of spMex67p previously identified as having a nuclear export
      activity can functionally substitute for the nuclear export activity at the C
      terminus of Crp79p. Although both Crp79p and spMex67p function to export mRNA,
      Crp79p does not substitute for all of spMex67p functions and probably is not a
      functional homologue of spMex67p. We propose that Crp79p is a nonessential mRNA
      export carrier in S. pombe.

PMID- 12181331
TI  - Downstream E-box-mediated regulation of the human telomerase reverse
      transcriptase (hTERT) gene transcription: evidence for an endogenous mechanism of
      transcriptional repression.
AB  - Regulation of the hTERT gene encoding the telomerase catalytic subunit plays an
      important role in human cell senescence, immortalization, and carcinogenesis. By
      examining the activity of various deleted or mutated hTERT promoter fragments, we
      show that an E-box element downstream of the transcription initiation site is
      critical to differential hTERT transcription between the telomerase/hTERT
      positive renal cell carcinoma cell line (RCC23) and its telomerase/hTERT-negative
      counterpart containing a transferred, normal chromosome 3 (RCC23+3). This E-box
      element mediated repression of hTERT transcription in RCC23+3 but not in RCC23. A
      copy number-dependent enhancement of the repression suggested active repression,
      rather than loss of activation, in RCC23+3. Endogenous expression levels of c-Myc
      or Mad1, which could activate or repress hTERT transcription when overexpressed,
      did not account for the differential hTERT transcription. Gel mobility shift
      assays identified the upstream stimulatory factors (USFs) as a major E-box
      binding protein complex in both RCC23 and RCC23+3 and, importantly, detected an
      RCC23+3-specific, E-box-binding factor that was distinct from the USF and Myc/Mad
      families. The E-box-mediated repression was also active in normal human
      fibroblasts and epithelial cells and inactive in some, but not all,
      telomerase/hTERT-positive cancer cells. These findings provide evidence for an
      endogenous, repressive mechanism that actively functions in telomerase/hTERT
      negative normal cells and becomes defective during carcinogenic processes, e.g.,
      by an inactivation of the telomerase repressor gene on chromosome 3.

PMID- 12181332
TI  - Cytochrome c release and mitochondria involvement in programmed cell death
      induced by acetic acid in Saccharomyces cerevisiae.
AB  - Evidence is presented that mitochondria are implicated in the previously
      described programmed cell death (PCD) process induced by acetic acid in
      Saccharomyces cerevisiae. In yeast cells undergoing a PCD process induced by
      acetic acid, translocation of cytochrome c (CytC) to the cytosol and reactive
      oxygen species production, two events known to be proapoptotic in mammals, were
      observed. Associated with these events, reduction in oxygen consumption and in
      mitochondrial membrane potential was found. Enzymatic assays showed that the
      activity of complex bc(1) was normal, whereas that of cytochrome c oxidase (COX)
      was strongly decreased. This decrease is in accordance with the observed
      reduction in the amounts of COX II subunit and of cytochromes a+a(3). The acetic
      acid-induced PCD process was found to be independent of oxidative phosphorylation
      because it was not inhibited by oligomycin treatment. The inability of S.
      cerevisiae mutant strains (lacking mitochondrial DNA, heme lyase, or ATPase) to
      undergo acetic acid-induced PCD and in the ATPase mutant (knockout in ATP10) the
      absence of CytC release provides further evidence that the process is mediated by
      a mitochondria-dependent apoptotic pathway. The understanding of the involvement
      of a mitochondria-dependent apoptotic pathway in S. cerevisiae PCD process will
      be most useful in the further elucidation of an ancestral pathway common to PCD
      in metazoans.

PMID- 12181333
TI  - Scd5p and clathrin function are important for cortical actin organization,
      endocytosis, and localization of sla2p in yeast.
AB  - SCD5 was identified as a multicopy suppressor of clathrin HC-deficient yeast.
      SCD5 is essential, but an scd5-Delta338 mutant, expressing Scd5p with a C
      terminal truncation of 338 amino acids, is temperature sensitive for growth.
      Further studies here demonstrate that scd5-Delta338 affects receptor-mediated and
      fluid-phase endocytosis and normal actin organization. The scd5-Delta338 mutant
      contains larger and depolarized cortical actin patches and a prevalence of G
      actin bars. scd5-Delta338 also displays synthetic negative genetic interactions
      with mutations in several other proteins important for cortical actin
      organization and endocytosis. Moreover, Scd5p colocalizes with cortical actin.
      Analysis has revealed that clathrin-deficient yeast also have a major defect in
      cortical actin organization and accumulate G-actin. Overexpression of SCD5
      partially suppresses the actin defect of clathrin mutants, whereas combining scd5
      Delta338 with a clathrin mutation exacerbates the actin and endocytic phenotypes.
      Both Scd5p and yeast clathrin physically associate with Sla2p, a homologue of the
      mammalian huntingtin interacting protein HIP1 and the related HIP1R. Furthermore,
      Sla2p localization at the cell cortex is dependent on Scd5p and clathrin
      function. Therefore, Scd5p and clathrin are important for actin organization and
      endocytosis, and Sla2p may provide a critical link between clathrin and the actin
      cytoskeleton in yeast, similar to HIP1(R) in animal cells.

PMID- 12181334
TI  - MEC3, MEC1, and DDC2 are essential components of a telomere checkpoint pathway
      required for cell cycle arrest during senescence in Saccharomyces cerevisiae.
AB  - When telomerase is absent and/or telomeres become critically short, cells undergo
      a progressive decline in viability termed senescence. The telomere checkpoint
      model predicts that cells will respond to a damaged or critically short telomere
      by transiently arresting and activating repair of the telomere. We examined the
      senescence of telomerase-deficient Saccharomyces cerevisiae at the cellular level
      to ask if the loss of telomerase activity triggers a checkpoint response. As
      telomerase-deficient mutants were serially subcultured, cells exhibited a
      progressive decline in average growth rate and an increase in the number of cells
      delayed in the G2/M stage of the cell cycle. MEC3, MEC1, and DDC2, genes
      important for the DNA damage checkpoint response, were required for the cell
      cycle delay in telomerase-deficient cells. In contrast, TEL1, RAD9, and RAD53,
      genes also required for the DNA damage checkpoint response, were not required for
      the G2/M delay in telomerase-deficient cells. We propose that the telomere
      checkpoint is distinct from the DNA damage checkpoint and requires a specific set
      of gene products to delay the cell cycle and presumably to activate telomerase
      and/or other telomere repair activities.

PMID- 12181336
TI  - Cytoplasmic localization of Wis1 MAPKK by nuclear export signal is important for
      nuclear targeting of Spc1/Sty1 MAPK in fission yeast.
AB  - Mitogen-activated protein kinase (MAPK) cascade is a ubiquitous signaling module
      that transmits extracellular stimuli through the cytoplasm to the nucleus; in
      response to activating stimuli, MAPKs translocate into the nucleus. Mammalian MEK
      MAPK kinases (MAPKKs) have in their N termini an MAPK-docking site and a nuclear
      export signal (NES) sequence, which are known to play critical roles in
      maintaining ERK MAPKs in the cytoplasm of unstimulated cells. Herein, we show
      that the Wis1 MAPKK of the stress-activated Spc1 MAPK cascade in fission yeast
      also has a MAPK-docking site and an NES sequence in its N-terminal domain.
      Unexpectedly, an inactivating mutation to the NES of chromosomal wis1(+) does not
      affect the subcellular localization of Spc1 MAPK, whereas this NES mutation
      disturbs the cytoplasmic localization of Wis1. However, when Wis1 is targeted to
      the nucleus by fusing to a nuclear localization signal sequence, stress-induced
      nuclear translocation of Spc1 is abrogated, indicating that cytoplasmic Wis1 is
      required for nuclear transport of Spc1 upon stress. Moreover, we have observed
      that a fraction of Wis1 translocates into the nucleus in response to stress.
      These results suggest that cytoplasmic localization of Wis1 MAPKK by its NES is
      important for stress signaling to the nucleus.

PMID- 12181335
TI  - Organizational diversity among distinct glycoprotein endoplasmic reticulum
      associated degradation programs.
AB  - Protein folding and quality control in the early secretory pathway function as
      posttranslational checkpoints in eukaryote gene expression. Herein, an aberrant
      form of the hepatic secretory protein alpha1-antitrypsin was stably expressed in
      a human embryonic kidney cell line to elucidate the mechanisms by which
      glycoprotein endoplasmic reticulum-associated degradation (GERAD) is administered
      in cells from higher eukaryotes. After biosynthesis, genetic variant PI Z
      underwent alternative phases of secretion and degradation, the latter of which
      was mediated by the proteasome. Degradation required release from calnexin- and
      asparagine-linked oligosaccharide modification by endoplasmic reticulum
      mannosidase I, the latter of which occurred as PI Z was bound to the molecular
      chaperone grp78/BiP. That a distinct GERAD program operates in human embryonic
      kidney cells was supported by the extent of PI Z secretion, apparent lack of
      polymerization, inability of calnexin to participate in the degradation process,
      and sequestration of the glycoprotein folding sensor UDP-glucose:glycoprotein
      glucosyltransferase in the Golgi complex. Because UDP-glucose:glycoprotein
      glucosyltransferase sustains calnexin binding, its altered distribution is
      consistent with a GERAD program that hinders the reentry of substrates into the
      calnexin cycle, allowing grp78/BiP to partner with a lectin, other than calnexin,
      in the recognition of a two-component GERAD signal to facilitate substrate
      recruitment. How the processing of a mutant protein, rather than the mutation
      itself, can contribute to disease pathogenesis, is discussed.

PMID- 12181337
TI  - Multiple functions of sterols in yeast endocytosis.
AB  - Sterols are essential factors for endocytosis in animals and yeast. To
      investigate the sterol structural requirements for yeast endocytosis, we created
      a variety of ergDelta mutants, each accumulating a distinct set of sterols
      different from ergosterol. Mutant erg2Deltaerg6Delta and erg3Deltaerg6Delta cells
      exhibit a strong internalization defect of the alpha-factor receptor (Ste2p).
      Specific sterol structures are necessary for pheromone-dependent receptor
      hyperphosphorylation, a prerequisite for internalization. The lack of
      phosphorylation is not due to a defect in Ste2p localization or in ligand
      receptor interaction. Contrary to most known endocytic factors, sterols seem to
      function in internalization independently of actin. Furthermore, sterol
      structures are required at a postinternalization step of endocytosis. ergDelta
      cells were able to take up the membrane marker FM4-64, but exhibited defects in
      FM4-64 movement through endosomal compartments to the vacuole. Therefore, there
      are at least two roles for sterols in endocytosis. Based on sterol analysis, the
      sterol structural requirements for these two processes were different, suggesting
      that sterols may have distinct functions at different places in the endocytic
      pathway. Interestingly, sterol structures unable to support endocytosis allowed
      transport of the glycosylphosphatidylinositol-anchored protein Gas1p from the
      endoplasmic reticulum to Golgi compartment.

PMID- 12181338
TI  - Yarrowia lipolytica cells mutant for the PEX24 gene encoding a peroxisomal
      membrane peroxin mislocalize peroxisomal proteins and accumulate membrane
      structures containing both peroxisomal matrix and membrane proteins.
AB  - Peroxins are proteins required for peroxisome assembly and are encoded by the PEX
      genes. Functional complementation of the oleic acid-nonutilizing strain mut1-1 of
      the yeast Yarrowia lipolytica has identified the novel gene, PEX24. PEX24 encodes
      Pex24p, a protein of 550 amino acids (61,100 Da). Pex24p is an integral membrane
      protein of peroxisomes that exhibits high sequence homology to two hypothetical
      proteins encoded by the open reading frames YHR150W and YDR479C of the
      Saccharomyces cerevisiae genome. Pex24p is detectable in wild-type cells grown in
      glucose-containing medium, and its levels are significantly increased by
      incubation of cells in oleic acid-containing medium, the metabolism of which
      requires intact peroxisomes. pex24 mutants are compromised in the targeting of
      both matrix and membrane proteins to peroxisomes. Although pex24 mutants fail to
      assemble functional peroxisomes, they do harbor membrane structures that contain
      subsets of peroxisomal proteins.

PMID- 12181340
TI  - Fluorescence resonance energy transfer detection of synaptophysin I and vesicle
      associated membrane protein 2 interactions during exocytosis from single live
      synapses.
AB  - To investigate the molecular interactions of synaptophysin I and vesicle
      associated membrane protein 2 (VAMP2)/synaptobrevin II during exocytosis, we have
      used time-lapse videomicroscopy to measure fluorescence resonance energy transfer
      in live neurons. For this purpose, fluorescent protein variants fused to
      synaptophysin I or VAMP2 were expressed in rat hippocampal neurons. We show that
      synaptophysin I and VAMP2 form both homo- and hetero-oligomers on the synaptic
      vesicle membrane. When exocytosis is stimulated with alpha-latrotoxin, VAMP2
      dissociates from synaptophysin I even in the absence of appreciable exocytosis,
      whereas synaptophysin I oligomers disassemble only upon incorporation of the
      vesicle with the plasma membrane. We propose that synaptophysin I has multiple
      roles in neurotransmitter release, regulating VAMP2 availability for the soluble
      N-ethylmaleimide-sensitive factor attachment protein receptor complex and
      possibly participating in the late steps of exocytosis.

PMID- 12181339
TI  - Dual regulation of actin rearrangement through lysophosphatidic acid receptor in
      neuroblast cell lines: actin depolymerization by Ca(2+)-alpha-actinin and
      polymerization by rho.
AB  - Lysophosphatidic acid (LPA) is a potent lipid mediator with actions on many cell
      types. Morphological changes involving actin polymerization are mediated by at
      least two cognate G protein-coupled receptors, LPA(1)/EDG-2 or LPA(2)/EDG-4.
      Herein, we show that LPA can also induce actin depolymerization preceding actin
      polymerization within single TR mouse immortalized neuroblasts. Actin
      depolymerization resulted in immediate loss of membrane ruffling, whereas actin
      polymerization resulted in process retraction. Each pathway was found to be
      independent: depolymerization mediated by intracellular calcium mobilization, and
      alpha-actinin activity and polymerization mediated by the activation of the small
      Rho GTPase. alpha-Actinin-mediated depolymerization seems to be involved in
      growth cone collapse of primary neurons, indicating a physiological significance
      of LPA-induced actin depolymerization. Further evidence for dual regulation of
      actin rearrangement was found by heterologous retroviral transduction of either
      lpa(1) or lpa(2) in B103 cells that neither express LPA receptors nor respond to
      LPA, to confer both forms of LPA-induced actin rearrangements. These results
      suggest that diverging intracellular signals from a single type of LPA receptor
      could regulate actin depolymerization, as well as polymerization, within a single
      cell. This dual actin rearrangement may play a novel, important role in
      regulation of the neuronal morphology and motility during brain development.

PMID- 12181341
TI  - The microtubule-destabilizing kinesin XKCM1 regulates microtubule dynamic
      instability in cells.
AB  - The dynamic activities of cellular microtubules (MTs) are tightly regulated by a
      balance between MT-stabilizing and -destabilizing proteins. Studies in Xenopus
      egg extracts have shown that the major MT destabilizer during interphase and
      mitosis is the kinesin-related protein XKCM1, which depolymerizes MT ends in an
      ATP-dependent manner. Herein, we examine the effects of both overexpression and
      inhibition of XKCM1 on the regulation of MT dynamics in vertebrate somatic cells.
      We found that XKCM1 is a MT-destabilizing enzyme in PtK2 cells and that XKCM1
      modulates cellular MT dynamics. Our results indicate that perturbation of XKCM1
      levels alters the catastrophe frequency and the rescue frequency of cellular MTs.
      In addition, we found that overexpression of XKCM1 or inhibition of KCM1 during
      mitosis leads to the formation of aberrant spindles and a mitotic delay. The
      predominant spindle defects from excess XKCM1 included monoastral and monopolar
      spindles, as well as small prometaphase-like spindles with improper chromosomal
      attachments. Inhibition of KCM1 during mitosis led to prometaphase spindles with
      excessively long MTs and spindles with partially separated poles and a radial MT
      array. These results show that KCM1 plays a critical role in regulating both
      interphase and mitotic MT dynamics in mammalian cells.

PMID- 12181342
TI  - Septin function in Candida albicans morphogenesis.
AB  - The septin proteins function in the formation of septa, mating projections, and
      spores in Saccharomyces cerevisiae, as well as in cell division and other
      processes in animal cells. Candida albicans septins were examined in this study
      for their roles in morphogenesis of this multimorphic, opportunistically
      pathogenic fungus, which can range from round budding yeast to elongated hyphae.
      C. albicans green fluorescent protein labeled septin proteins localized to a
      tight ring at the bud and pseudohyphae necks and as a more diffuse array in
      emerging germ tubes of hyphae. Deletion analysis demonstrated that the C.
      albicans homologs of the S. cerevisiae CDC3 and CDC12 septins are essential for
      viability. In contrast, the C. albicans cdc10Delta and cdc11Delta mutants were
      viable but displayed conditional defects in cytokinesis, localization of cell
      wall chitin, and bud morphology. The mutant phenotypes were not identical,
      however, indicating that these septins carry out distinct functions. The viable
      septin mutants could be stimulated to undergo hyphal morphogenesis but formed
      hyphae with abnormal curvature, and they differed from wild type in the selection
      of sites for subsequent rounds of hyphal formation. The cdc11Delta mutants were
      also defective for invasive growth when embedded in agar. These results further
      extend the known roles of the septins by demonstrating that they are essential
      for the proper morphogenesis of C. albicans during both budding and filamentous
      growth.

PMID- 12181343
TI  - The septation apparatus, an autonomous system in budding yeast.
AB  - Actomyosin ring contraction and chitin primary septum deposition are
      interdependent processes in cell division of budding yeast. By fusing Myo1p, as
      representative of the contractile ring, and Chs2p for the primary septum, to
      different fluorescent proteins we show herein that the two processes proceed
      essentially at the same location and simultaneously. Chs2p differs from Myo1p in
      that it reflects the changes in shape of the plasma membrane to which it is
      attached and in that it is packed after its action into visible endocytic
      vesicles for its disposal. To ascertain whether this highly coordinated system
      could function independently of other cell cycle events, we reexamined the septum
      like structures made by the septin mutant cdc3 at various sites on the cell
      cortex at the nonpermissive temperature. With the fluorescent fusion proteins
      mentioned above, we observed that in cdc3 at 37 degrees C both Myo1p and Chs2p
      colocalize at different spots of the cell cortex. A contraction of the Myo1p
      patch could also be detected, as well as that of a Chs2p patch, with subsequent
      appearance of vesicles. Furthermore, the septin Cdc12p, fused with yellow or cyan
      fluorescent protein, also colocalized with Myo1p and Chs2p at the aberrant
      locations. The formation of delocalized septa did not require nuclear division.
      We conclude that the septation apparatus, composed of septins, contractile ring,
      and the chitin synthase II system, can function at ectopic locations autonomously
      and independently of cell division, and that it can recruit the other elements
      necessary for the formation of secondary septa.

PMID- 12181344
TI  - Overexpression of yeast Hsp110 homolog Sse1p suppresses ydj1-151
      thermosensitivity and restores Hsp90-dependent activity.
AB  - The Saccharomyces cerevisiae heat-shock protein (Hsp)40, Ydj1p, is involved in a
      variety of cellular activities that control polypeptide fate, such as folding and
      translocation across intracellular membranes. To elucidate the mechanism of Ydj1p
      action, and to identify functional partners, we screened for multicopy
      suppressors of the temperature-sensitive ydj1-151 mutant and identified a yeast
      Hsp110, SSE1. Overexpression of Sse1p also suppressed the folding defect of v-Src
      kinase in the ydj1-151 mutant and partially reversed the alpha-factor
      translocation defect. SSE1-dependent suppression of ydj1-151 thermosensitivity
      required the wild-type ATP-binding domain of Sse1p. However, the Sse1p mutants
      maintained heat-denatured firefly luciferase in a folding-competent state in
      vitro and restored human androgen receptor folding in sse1 mutant cells. Because
      the folding of both v-Src kinase and human androgen receptor in yeast requires
      the Hsp90 complex, these data suggest that Ydj1p and Sse1p are interacting
      cochaperones in the Hsp90 complex and facilitate Hsp90-dependent activity.

PMID- 12181345
TI  - Clastosome: a subtype of nuclear body enriched in 19S and 20S proteasomes,
      ubiquitin, and protein substrates of proteasome.
AB  - Nuclear bodies represent a heterogeneous class of nuclear structures. Herein, we
      describe that a subset of nuclear bodies is highly enriched in components of the
      ubiquitin-proteasome pathway of proteolysis. We coined the term clastosome (from
      the Greek klastos, broken and soma, body) to refer to this type of nuclear body.
      Clastosomes contain a high concentration of 1) ubiquitin conjugates, 2) the
      proteolytically active 20S core and the 19S regulatory complexes of the 26S
      proteasome, and 3) protein substrates of the proteasome. Although detected in a
      variety of cell types, clastosomes are scarce under normal conditions; however,
      they become more abundant when proteasomal activity is stimulated. In contrast,
      clastosomes disappear when cells are treated with proteasome inhibitors. Protein
      substrates of the proteasome that are found concentrated in clastosomes include
      the short-lived transcription factors c-Fos and c-Jun, adenovirus E1A proteins,
      and the PML protein. We propose that clastosomes are sites where proteolysis of a
      variety of protein substrates is taking place.

PMID- 12181346
TI  - Dissection of transient oxidative stress response in Saccharomyces cerevisiae by
      using DNA microarrays.
AB  - Yeast cells were grown in glucose-limited chemostat cultures and forced to switch
      to a new carbon source, the fatty acid oleate. Alterations in gene expression
      were monitored using DNA microarrays combined with bioinformatics tools, among
      which was included the recently developed algorithm REDUCE. Immediately after the
      switch to oleate, a transient and very specific stress response was observed,
      followed by the up-regulation of genes encoding peroxisomal enzymes required for
      fatty acid metabolism. The stress response included up-regulation of genes coding
      for enzymes to keep thioredoxin and glutathione reduced, as well as enzymes
      required for the detoxification of reactive oxygen species. Among the genes
      coding for various isoenzymes involved in these processes, only a specific subset
      was expressed. Not the general stress transcription factors Msn2 and Msn4, but
      rather the specific factor Yap1p seemed to be the main regulator of the stress
      response. We ascribe the initiation of the oxidative stress response to a
      combination of poor redox flux and fatty acid-induced uncoupling of the
      respiratory chain during the metabolic reprogramming phase.

PMID- 12181347
TI  - Function of dynein and dynactin in herpes simplex virus capsid transport.
AB  - After fusion of the viral envelope with the plasma membrane, herpes simplex virus
      type 1 (HSV1) capsids are transported along microtubules (MTs) from the cell
      periphery to the nucleus. The motor ATPase cytoplasmic dynein and its
      multisubunit cofactor dynactin mediate most transport processes directed toward
      the minus-ends of MTs. Immunofluorescence microscopy experiments demonstrated
      that HSV1 capsids colocalized with cytoplasmic dynein and dynactin. We blocked
      the function of dynein by overexpressing the dynactin subunit dynamitin, which
      leads to the disruption of the dynactin complex. We then infected such cells with
      HSV1 and measured the efficiency of particle binding, virus entry, capsid
      transport to the nucleus, and the expression of immediate-early viral genes. High
      concentrations of dynamitin and dynamitin-GFP reduced the number of viral capsids
      transported to the nucleus. Moreover, viral protein synthesis was inhibited,
      whereas virus binding to the plasma membrane, its internalization, and the
      organization of the MT network were not affected. We concluded that incoming HSV1
      capsids are propelled along MTs by dynein and that dynein and dynactin are
      required for efficient viral capsid transport to the nucleus.

PMID- 12181348
TI  - Structure of the Golgi and distribution of reporter molecules at 20 degrees C
      reveals the complexity of the exit compartments.
AB  - Incubating cells at 20 degrees C blocks transport out of the Golgi complex and
      amplifies the exit compartments. We have used the 20 degrees C block, followed by
      EM tomography and serial section reconstruction, to study the structure of Golgi
      exit sites in NRK cells. The dominant feature of Golgi structure in temperature
      blocked cells is the presence of large bulging domains on the three trans-most
      cisternae. These domains extend laterally from the stack and are continuous with
      "cisternal" domains that maintain normal thickness and alignment with the other
      stacked Golgi cisternae. The bulging domains do not resemble the perpendicularly
      extending tubules associated with the trans-cisternae of control cells. Such
      tubules are completely absent in temperature-blocked cells. The three cisternae
      with bulging domains can be identified as trans by their association with
      specialized ER and the presence of clathrin-coated buds on the trans-most
      cisterna only. Immunogold labeling and immunoblots show a significant degradation
      of a medial- and a trans-Golgi marker with no evidence for their redistribution
      within the Golgi or to other organelles. These data suggest that exit from the
      Golgi occurs directly from three trans-cisternae and that specialized ER plays a
      significant role in trans-Golgi function.

PMID- 12181349
TI  - Identification of the functional domains of yeast sorting nexins Vps5p and
      Vps17p.
AB  - Sorting nexins (Snxs) are a recently discovered family of conserved hydrophilic
      cytoplasmic proteins that have been found associated with membranes of the
      endocytic system and that are implicated in the trafficking of many endosomal
      membrane proteins, including the epidermal growth factor receptor and transferrin
      receptor. Snx proteins are partly defined by the presence of a p40 phox homology
      domain that has recently been shown to bind phosphatidylinositol 3-phosphate.
      Most Snx proteins also contain a predicted coiled-coils domain in the carboxyl
      terminal half of the protein and have been shown to form dimers with other
      members of the Snx family. The yeast sorting nexins Vps5p and Vps17p form a dimer
      and are also components of the retromer complex that mediates endosome-to-Golgi
      transport of the carboxypeptidase Y receptor Vps10p. To functionally define the
      different domains of the yeast sorting nexins Vps5p and Vps17p, we have generated
      various truncations to examine the role that the different domains of
      Vps5p/Vps17p play in their respective functions. Herein, we show that the C
      terminal halves of Vps5p and Vps17p, which contain the coiled-coils domains, are
      necessary and sufficient for their interaction. We have also mapped the retromer
      assembly domain to the N-terminal half of Vps5p and found that binding of Vps5p
      by Vps17p synergizes the interaction between Vps5p and other retromer components.
      Additionally, we have examined which domain(s) of Vps5p is necessary for membrane
      association.

PMID- 12181350
TI  - Cross-linking CD98 promotes integrin-like signaling and anchorage-independent
      growth.
AB  - CD98, an early marker of T-cell activation, is an important regulator of integrin
      mediated adhesion events. Previous studies suggest that CD98 is coupled to both
      cellular activation and transformation and is involved in the pathogenesis of
      viral infection, inflammatory disease, and cancer. Understanding of the molecular
      mechanisms underlying CD98 activity may have far-reaching practical applications
      in the development of novel therapeutic strategies in these disease states. Using
      small cell lung cancer cell lines, which are nonadherent, nonpolarized, and
      highly express CD98, we show that, in vitro, under physiological conditions, CD98
      is constitutively associated with beta1 integrins regardless of activation
      status. Cross-linking CD98 with the monoclonal antibody 4F2 stimulated
      phosphatidylinositol (PI) 3-kinase, PI(3,4,5)P(3), and protein kinase B in the
      absence of integrin ligation or extracellular matrix engagement. Furthermore,
      cross-linking CD98 promoted anchorage-independent growth. Using fibroblasts
      derived from beta1 integrin null stem cells (GD25), wild-type GD25beta1, or GD25
      cells expressing a mutation preventing beta1 integrin-dependent FAK
      phosphorylation, we demonstrate that a functional beta1 integrin is required for
      CD98 signaling. We propose that by cross-linking CD98, it acts as a "molecular
      facilitator" in the plasma membrane, clustering beta1 integrins to form high
      density complexes. This results in integrin activation, integrin-like signaling,
      and anchorage-independent growth. Activation of PI 3-kinase may, in part, explain
      cellular transformation seen on overexpressing CD98. These results may provide a
      paradigm for events involved in such diverse processes as inflammation and viral
      induced cell fusion.

PMID- 12181351
TI  - Molecular cloning and functional expression of the rat 175-kDa hyaluronan
      receptor for endocytosis.
AB  - We recently purified the rat liver hyaluronan receptor for endocytosis (HARE) and
      found abundant expression of 175- and approximately 300-kDa HARE species in
      sinusoidal endothelial cells of the liver, spleen, and lymph nodes. We report
      herein the first cloning and functional expression of the rat 175-kDa HARE.
      Peptide sequences were obtained from the purified 175-kDa HARE, and degenerate
      oligonucleotide primers were designed for reverse transcription-polymerase chain
      reaction and cDNA cloning. Results of 5'-rapid amplification of cDNA ends,
      Northern analysis, N-terminal sequence, and antibody reactivity analyses
      indicated the absence of mRNA directly encoding the 175-kDa HARE. This protein is
      most likely derived from a larger precursor. Accordingly, we constructed an
      artificial 4.7-kb cDNA encoding the 1431 amino acid 175-kDa HARE. The predicted
      type I membrane protein has a mass of 156,393 Da and a pI of 7.86. The 175-kDa
      HARE cDNA, fused to the N-terminal leader sequence of the Ig kappa-chain, was
      transfected transiently into COS-7 cells and stably into SK-Hep-1 cells,
      respectively, to assess hyaluronan or hyaluronic acid (HA)-binding activity and
      endocytosis. In both cases, HARE expression and HA-binding activity were
      detected. Furthermore, stable SK-175HARE cells demonstrated specific endocytosis
      of (125)I-HA and receptor recycling. Fluorescence-activated cell sorting analysis
      confirmed that recombinant HARE was expressed on the cell surface and that
      fluorescent HA uptake was inhibited by a specific blocking monoclonal antibody
      against HARE. Additionally, HARE was substantially colocalized with clathrin, but
      not with internalized HA that was delivered to lysosomes. The results confirm
      that recombinant 175-kDa HARE is an authentic endocytic receptor for HA and that
      this receptor can function independently of the approximately 300-kDa HARE. HARE
      is the first functionally identified member of a protein family that shares a
      similar organization of Fasciclin, epidermal growth factor-like, Xlink, and
      transmembrane domains.

PMID- 12181352
TI  - The MEK kinase Ssk2p promotes actin cytoskeleton recovery after osmotic stress.
AB  - Saccharomyces cerevisiae adapts to osmotic stress through the activation of a
      conserved high-osmolarity growth (HOG) mitogen-activated protein (MAP) kinase
      pathway. Transmission through the HOG pathway is very well understood, yet other
      aspects of the cellular response to osmotic stress remain poorly understood, most
      notably regulation of actin organization. The actin cytoskeleton rapidly
      disassembles in response to osmotic insult and is induced to reassemble only
      after osmotic balance with the environment is reestablished. Here, we show that
      one of three MEK kinases of the HOG pathway, Ssk2p, is specialized to facilitate
      actin cytoskeleton reassembly after osmotic stress. Within minutes of cells'
      experiencing osmotic stress or catastrophic disassembly of the actin cytoskeleton
      through latrunculin A treatment, Ssk2p concentrates in the neck of budding yeast
      cells and concurrently forms a 1:1 complex with actin. These observations suggest
      that Ssk2p has a novel, previously undescribed function in sensing damage to the
      actin cytoskeleton. We also describe a second function for Ssk2p in facilitating
      reassembly of a polarized actin cytoskeleton at the end of the cell cycle, a
      prerequisite for efficient cell cycle completion. Loss of Ssk2p, its kinase
      activity, or its ability to localize and interact with actin led to delays in
      actin recovery and a resulting delay in cell cycle completion. These unique
      capabilities of Ssk2p are activated by a novel mechanism that does not involve
      known components of the HOG pathway.

PMID- 12181353
TI  - The Shb adaptor protein binds to tyrosine 766 in the FGFR-1 and regulates the
      Ras/MEK/MAPK pathway via FRS2 phosphorylation in endothelial cells.
AB  - Stimulation of fibroblast growth factor receptor-1 (FGFR-1) is known to result in
      phosphorylation of tyrosine 766 and the recruitment and subsequent activation of
      phospholipase C-gamma (PLC-gamma). To assess the role of tyrosine 766 in
      endothelial cell function, we generated endothelial cells expressing a chimeric
      receptor, composed of the extracellular domain of the PDGF receptor-alpha and the
      intracellular domain of FGFR-1. Mutation of tyrosine 766 to phenylalanine
      prevented PLC-gamma activation and resulted in a reduced phosphorylation of FRS2
      and reduced activation of the Ras/MEK/MAPK pathway relative to the wild-type
      chimeric receptor. However, FGFR-1-mediated MAPK activation was not dependent on
      PKC activation or intracellular calcium, both downstream mediators of PLC-gamma
      activation. We report that the adaptor protein Shb is also able to bind tyrosine
      766 in the FGFR-1, via its SH2 domain, resulting in its subsequent
      phosphorylation. Overexpression of an SH2 domain mutant Shb caused a dramatic
      reduction in FGFR-1-mediated FRS2 phosphorylation with concomitant perturbment of
      the Ras/MEK/MAPK pathway. Expression of the chimeric receptor mutant and the Shb
      SH2 domain mutant resulted in a similar reduction in FGFR-1-mediated
      mitogenicity. We conclude, that Shb binds to tyrosine 766 in the FGFR-1 and
      regulates FGF-mediated mitogenicity via FRS2 phosphorylation and the subsequent
      activation of the Ras/MEK/MAPK pathway.

PMID- 12181354
TI  - c-erbB2-induced disruption of matrix adhesion and morphogenesis reveals a novel
      role for protein kinase B as a negative regulator of alpha(2)beta(1) integrin
      function.
AB  - Overexpression of the growth factor receptor subunit c-erbB2, leading to its
      ligand-independent homodimerization and activation, has been implicated in the
      pathogenesis of mammary carcinoma. Here, we have examined the effects of c-erbB2
      on the adhesive properties of a mammary epithelial cell line, HB2/tnz34, in which
      c-erbB2 homodimerization can be induced by means of a transfected hybrid "trk
      neu" construct. trk-neu consists of the extracellular domain of the trkA nerve
      growth factor (NGF) receptor fused to the transmembrane and cytoplasmic domains
      of c-erbB2, allowing NGF-induced c-erbB2 homodimer signaling. Both spreading and
      adhesion on collagen surfaces were impaired on c-erbB2 activation in HB2/tnz34
      cells. Antibody-mediated stimulation of alpha(2)beta(1) integrin function
      restored adhesion, suggesting a direct role for c-erbB2 in integrin inactivation.
      Using pharmacological inhibitors and transient transfections, we identified
      signaling pathways required for suppression of integrin function by c-erbB2.
      Among these was the MEK-ERK pathway, previously implicated in integrin
      inactivation. However, we could also show that downstream of phosphoinositide-3
      kinase (PI3K), protein kinase B (PKB) acted as a previously unknown, potent
      inhibitor of integrin function and mediator of the disruptive effects of c-erbB2
      on adhesion and morphogenesis. The integrin-linked kinase, previously identified
      as a PKB coactivator, was also found to be required for integrin inactivation by
      c-erbB2. In addition, the PI3K-dependent mTOR/S6 kinase pathway was shown to
      mediate c-erbB2-induced inhibition of adhesion (but not spreading) independently
      of PKB. Overexpression of MEK1 or PKB suppressed adhesion without requirement for
      c-erbB2 activation, suggesting that these two pathways partake in integrin
      inhibition by targeting common downstream effectors. These results demonstrate a
      major novel role for PI3K and PKB in regulation of integrin function.

PMID- 12181355
TI  - Release of hepatocyte growth factor from mechanically stretched skeletal muscle
      satellite cells and role of pH and nitric oxide.
AB  - Application of mechanical stretch to cultured adult rat muscle satellite cells
      results in release of hepatocyte growth factor (HGF) and accelerated entry into
      the cell cycle. Stretch activation of cultured rat muscle satellite cells was
      observed only when medium pH was between 7.1 and 7.5, even though activation of
      satellite cells was accelerated by exogenous HGF over a pH range from 6.9 to 7.8.
      Furthermore, HGF was only released in stretched cultures when the pH of the
      medium was between 7.1 and 7.4. Conditioned medium from stretched satellite cell
      cultures stimulated activation of unstretched satellite cells, and the addition
      of anti-HGF neutralizing antibodies to stretch-conditioned medium inhibited the
      stretch activation response. Conditioned medium from satellite cells that were
      stretched in the presence of nitric-oxide synthase (NOS) inhibitor N(omega)-nitro
      L-arginine methyl ester hydrochloride did not accelerate activation of
      unstretched control satellite cells, and HGF was not released into the medium.
      Conditioned medium from unstretched cells that were treated with a nitric oxide
      donor, sodium nitroprusside dihydrate, was able to accelerate the activation of
      satellite cells in vitro, and HGF was found in the conditioned medium. Immunoblot
      analysis indicated that both neuronal and endothelial NOS isoforms were present
      in satellite cell cultures. Furthermore, assays of NOS activity in stretched
      satellite cell cultures demonstrated that NOS is stimulated when satellite cells
      are stretched in vitro. These experiments indicate that stretch triggers an
      intracellular cascade of events, including nitric oxide synthesis, which results
      in HGF release and satellite cell activation.

PMID- 12181356
TI  - beta-Tubulin C354 mutations that severely decrease microtubule dynamics do not
      prevent nuclear migration in yeast.
AB  - Microtubule dynamics are influenced by interactions of microtubules with cellular
      factors and by changes in the primary sequence of the tubulin molecule. Mutations
      of yeast beta-tubulin C354, which is located near the binding site of some
      antimitotic compounds, reduce microtubule dynamicity greater than 90% in vivo and
      in vitro. The resulting intrinsically stable microtubules allowed us to determine
      which, if any, cellular processes are dependent on dynamic microtubules. The
      average number of cytoplasmic microtubules decreased from 3 in wild-type to 1 in
      mutant cells. The single microtubule effectively located the bud site before bud
      emergence. Although spindles were positioned near the bud neck at the onset of
      anaphase, the mutant cells were deficient in preanaphase spindle alignment along
      the mother-bud axis. Spindle microtubule dynamics and spindle elongation rates
      were also severely depressed in the mutants. The pattern and extent of
      cytoplasmic microtubule dynamics modulation through the cell cycle may reveal the
      minimum dynamic properties required to support growth. The ability to alter
      intrinsic microtubule dynamics and determine the in vivo phenotype of cells
      expressing the mutant tubulin provides a critical advance in assessing the
      dynamic requirements of an essential gene function.

PMID- 12181358
TI  - Association of PI-3 kinase with PAK1 leads to actin phosphorylation and
      cytoskeletal reorganization.
AB  - The family of p21-activated kinases (PAKs) have been implicated in the
      rearrangement of actin cytoskeleton by acting downstream of the small GTPases Rac
      and Cdc42. Here we report that even though Cdc42/Rac1 or Akt are not activated,
      phosphatidylinositol-3 (PI-3) kinase activation induces PAK1 kinase activity.
      Indeed, we demonstrate that PI-3 kinase associates with the N-terminal regulatory
      domain of PAK1 (amino acids 67-150) leading to PAK1 activation. The association
      of the PI-3 kinase with the Cdc42/Rac1 binding-deficient PAK1(H83,86L) confirms
      that the small GTPases are not involved in the PI-3 kinase-PAK1 interaction.
      Furthermore, PAK1 was activated in cells expressing the dominant-negative forms
      of Cdc42 or Rac1. Additionally, we show that PAK1 phosphorylates actin, resulting
      in the dissolution of stress fibers and redistribution of microfilaments. The
      phosphorylation of actin was inhibited by the kinase-dead PAK1(K299R) or the PAK1
      autoinhibitory domain (PAK1(83-149)), indicating that PAK1 was responsible for
      actin phosphorylation. We conclude that the association of PI-3 kinase with PAK1
      regulates PAK1 kinase activity through a Cdc42/Rac1-independent mechanism leading
      to actin phosphorylation and cytoskeletal reorganization.

PMID- 12181357
TI  - Cell stress and MEKK1-mediated c-Jun activation modulate NFkappaB activity and
      cell viability.
AB  - Chemotherapeutic agents such as cisplatin induce persistent activation of N
      terminal c-Jun Kinase, which in turn mediates induction of apoptosis. By using a
      common MAPK Kinase, MEKK1, cisplatin also activates the survival transcription
      factor NFkappaB. We have found a cross-talk between c-Jun expression and NFkappaB
      transcriptional activation in response to cisplatin. Fibroblast derived from c
      jun knock out mice are more resistant to cisplatin-induced cell death, and this
      survival advantage is mediated by upregulation of NFkappaB-dependent
      transcription and expression of MIAP3. This process can be reverted by ectopic
      expression of c-Jun in c-jun(-/-) fibroblasts, which decreases p65
      transcriptional activity back to normal levels. Negative regulation of NFkappaB
      dependent transcription by c-jun contributes to cisplatin-induced cell death,
      which suggests that inhibition of NFkappaB may potentiate the antineoplastic
      effect of conventional chemotherapeutic agents.

PMID- 12181360
TI  - Exercise, genetics, and blood pressure: focus on "physical exercise and blood
      pressure with reference to the angiotensinogen M235T polymorphism" and on
      "angiotensinogen M235T polymorphism associates with exercise hemodynamics in
      postmenopausal women".

PMID- 12181359
TI  - Role of the Rab GTP-binding protein Ypt3 in the fission yeast exocytic pathway
      and its connection to calcineurin function.
AB  - A genetic screen for mutations synthetically lethal with fission yeast
      calcineurin deletion led to the identification of Ypt3, a homolog of mammalian
      Rab11 GTP-binding protein. A mutant with the temperature-sensitive ypt3-i5 allele
      showed pleiotropic phenotypes such as defects in cytokinesis, cell wall
      integrity, and vacuole fusion, and these were exacerbated by FK506-treatment, a
      specific inhibitor of calcineurin. Green fluorescent protein (GFP)-tagged Ypt3
      showed cytoplasmic staining that was concentrated at growth sites, and this
      polarized localization required the actin cytoskeleton. It was also detected as a
      punctate staining in an actin-independent manner. Electron microscopy revealed
      that ypt3-i5 mutants accumulated aberrant Golgi-like structures and putative post
      Golgi vesicles, which increased remarkably at the restrictive temperature.
      Consistently, the secretion of GFP fused with the pho1(+) leader peptide (SPL
      GFP) was abolished at the restrictive temperature in ypt3-i5 mutants. FK506
      treatment accentuated the accumulation of aberrant Golgi-like structures and
      caused a significant decrease of SPL-GFP secretion at a permissive temperature.
      These results suggest that Ypt3 is required at multiple steps of the exocytic
      pathway and its mutation affects diverse cellular processes and that calcineurin
      is functionally connected to these cellular processes.

PMID- 12181361
TI  - Differential expression of NAT1 translational repressor during development of
      bovine intramuscular adipocytes.
AB  - This study was undertaken to test for differential gene expression in
      intramuscular adipocytes during fat deposition of feedlot steers. Angus x
      Hereford steers (n = 50) were fed a high-energy concentrate ration ad libitum for
      20 (n = 5), 86 (n = 15), 121 (n = 15), and 146 days (n = 15) to obtain various
      degrees of intramuscular adipocyte development. Carcass traits were significantly
      different (P < 0.05) between the groups. Intramuscular adipose tissue was excised
      from the longissimus dorsi and snap frozen in liquid nitrogen. Pooled samples of
      total RNA representing each group were analyzed by differential-display
      polymerase chain reaction using 200 primer combinations comprising 20 arbitrary
      (5') and 10 anchor (3') oligonucleotides. Bands (n = 70) representing putative
      differences among treatment groups were excised, sequenced, and subjected to
      BLAST homology search. From these, 40 contained significant homology to known
      genes. One was of particular interest, the translational repressor NAT1 (novel
      APOBEC-1 target-1). NAT1 mRNA was quantified in individual animals to confirm
      differential expression among treatment groups. Results indicate that NAT1
      message is more abundant (P < 0.05) in intramuscular adipocytes of younger/leaner
      animals.

PMID- 12181362
TI  - Genome-wide linkage scan for exercise stroke volume and cardiac output in the
      HERITAGE Family Study.
AB  - A genome-wide linkage scan was performed for genes affecting submaximal exercise
      cardiac output (Q) and stroke volume (SV) in the sedentary state and their
      responses to a standardized 20-wk endurance training program. A total of 509
      polymorphic markers were used, and 328 pairs of siblings from 99 white nuclear
      families and 102 sibling pairs from 105 black family units were available. Q and
      SV were measured in relative steady state during exercise at 50 W (Q50 and SV50,
      respectively). Baseline phenotypes were adjusted for age, sex, and body surface
      area (BSA), and the training responses (post-training - baseline, Delta) were
      adjusted for age, sex, baseline BSA, and baseline value of the phenotype. Three
      analytical strategies were used: a multipoint variance components linkage
      analysis using all the family data, and regression-based single- and multipoint
      linkage analyses using pairs of siblings. In whites, baseline SV50 and DeltaSV50
      showed promising linkages (P < 0.0023) with markers on chromosomes 14q31.1 and
      10p11.2, respectively. Suggestive evidence of linkage (0.01 > P > 0.0023) for
      DeltaSV50 and Delta Q50 was detected on chromosome 2q31.1 and for baseline SV50
      and Q50 on chromosome 9q32-q33. In blacks, markers on 18q11.2 showed promising
      linkages with baseline Q50. Suggestive evidence of linkage was found in three
      regions for baseline SV50 (1p21.3, 3q13.3, 12q13.2) and one for baseline SV50 and
      Q50 (10p14). All these chromosomal regions include several potential candidate
      genes and therefore warrant further studies in the HERITAGE cohort and other
      studies.

PMID- 12181363
TI  - Angiotensinogen M235T polymorphism associates with exercise hemodynamics in
      postmenopausal women.
AB  - We sought to determine whether the M235T angiotensinogen (AGT) polymorphism,
      either interacting with habitual physical activity (PA) levels or independently,
      was associated with cardiovascular (CV) hemodynamics during maximal and
      submaximal exercise. Sixty-one healthy postmenopausal women (16 sedentary, 21
      physically active, and 24 endurance athletes) had heart rate (HR), blood pressure
      (BP), cardiac output, stroke volume (SV), total peripheral resistance (TPR), and
      arteriovenous O2 difference (a-vDO2) assessed during 40, 60, 80, and
      approximately 100% of VO2 max treadmill exercise. VO2 max did not differ among
      AGT genotype groups; however, maximal HR was 14 beats/min higher in AGT TT than
      MM genotype women (P < 0.05). AGT TT genotype women also had 19 beats/min higher
      HR during approximately 100% VO2 max exercise than AGT MM genotype women (P =
      0.008). AGT genotype also interacted with habitual PA levels to associate with
      systolic BP and a-vDO2 during approximately 100% VO2 max exercise (both P <
      0.01). AGT TT genotype women had 11 beats/min higher HR during submaximal
      exercise than MM genotype women (P < 0.05). AGT genotype interacted with habitual
      PA levels to associate with systolic BP during submaximal exercise (P = 0.009).
      AGT genotype, independently or interacting with habitual PA levels, did not
      associate significantly with diastolic BP, cardiac output, SV, or TPR during
      maximal or submaximal exercise. Thus this common genetic variant in the renin
      angiotensin system appears to associate, both interactively with habitual PA
      levels and independently, with HR, systolic BP, and a-vDO2 responses to maximal
      and submaximal exercise in postmenopausal women.

PMID- 12181364
TI  - Physical exercise and blood pressure with reference to the angiotensinogen M235T
      polymorphism.
AB  - We investigated the role of the angiotensinogen (AGT) gene M235T polymorphism in
      determining blood pressure (BP) response to moderate intensity exercise in a 6-yr
      randomized controlled trial in 140 middle-aged men. Sitting, supine, and standing
      blood pressures were measured annually. Of the randomized men, 86% participated
      in the trial for 6 yr. Submaximal cardiorespiratory fitness increased by 16% in
      the exercise group. In the M homozygotes, sitting systolic BP decreased by 1.0
      mmHg in the exercise but increased by 14.6 mmHg in the reference group (P = 0.007
      for net effect). Sitting and supine diastolic BP decreased by 6.2 and 3.3 mmHg in
      the exercise but increased by 2.8 and 3.2 mmHg in the reference group (P = 0.026
      and 0.024 for net effects), respectively. Regular moderate intensity exercise
      attenuates aging-related increase in systolic BP and decreases diastolic BP among
      the M homozygotes of the AGT gene M235T polymorphism.

PMID- 12181365
TI  - RNA interference of peroxisome-related genes in C. elegans: a new model for human
      peroxisomal disorders.
AB  - RNA-mediated interference (RNAi) for the posttranscriptional silencing of genes
      was used to evaluate the importance of various peroxisomal enzymes and peroxins
      for the development of Caenorhabditis elegans and to compare the roles of these
      proteins in the nematode to their roles in yeasts and humans. The nematode
      counterparts of the human ATP-binding cassette half-transporters, the enzymes
      alkyldihydroxyacetonephosphate synthase and Delta(3,5)-Delta (2,4)-dienoyl-CoA
      isomerase, the receptors for peroxisomal membrane and matrix proteins (Pex19p and
      Pex5p), and components of the docking and translocation machineries for matrix
      proteins (Pex13p and Pex12p) are essential for the development of C. elegans.
      Unexpectedly, RNAi silencing of the acyl-CoA synthetase-mediated activation of
      fatty acids, the alpha- and beta-oxidation of fatty acids, the intraperoxisomal
      decomposition of hydrogen peroxide, and the peroxins Pex1p, Pex2p, and Pex6p had
      no apparent effect on C. elegans development. The described analysis of
      functional gene knockouts through RNAi provides a basis for the use of C. elegans
      as a valuable model system with which to study the molecular and physiological
      defects underlying the human peroxisomal disorders.

PMID- 12181366
TI  - Quantitative assessment of ground squirrel mRNA levels in multiple stages of
      hibernation.
AB  - Hibernators in torpor dramatically reduce their metabolic, respiratory, and heart
      rates and core body temperature. These extreme physiological conditions are
      frequently and rapidly reversed during the winter hibernation season via
      endogenous mechanisms. This phenotype must derive from regulated expression of
      the hibernator's genome; to identify its molecular components, a cDNA subtraction
      was used to enrich for seasonally upregulated mRNAs in liver of golden-mantled
      ground squirrels. The relative steady-state levels for seven mRNAs identified by
      this screen, plus five others, were measured and analyzed for seasonal and stage
      specific differences using kinetic RT-PCR. Four mRNAs show seasonal upregulation
      in which all five winter stages differ significantly from and are higher than
      summer (alpha2-macroglobulin, apolipoprotein A1, cathepsin H, and thyroxine
      binding globulin). One of these mRNAs, alpha2-macroglobulin, varies during the
      winter stages with significantly lower levels at late torpor. None of the 12
      mRNAs increased during torpor. The implications for these newly recognized
      upregulated mRNAs for hibernation as well as more global issues of maintaining
      steady-state levels of mRNA during torpor are discussed.

PMID- 12181367
TI  - Gene expression changes during mouse skeletal myoblast differentiation revealed
      by transcriptional profiling.
AB  - Studies described here utilize high-density oligonucleotide arrays to
      characterize changes in global mRNA expression patterns during proliferation,
      cell cycle withdrawal, and terminal differentiation in mouse C2C12 myoblasts.
      Statistical analyses revealed 629 sequences differentially regulated between
      proliferating and differentiating myoblasts. These genes were clustered using
      self-organizing maps to identify sets of coregulated genes and were assigned to
      functional categories that were analyzed for distribution across expression
      clusters. Clusters were identified with statistically significant enrichment of
      functional categories including muscle contraction, cell adhesion, extracellular
      matrix function, cellular metabolism, mitochondrial transport, DNA replication,
      cell cycle control, mRNA transcription, and unexpectedly, immune regulation. In
      addition, functional category enrichment data can be used to predict gene
      function for numerous differentially regulated expressed sequence tags. The
      results provide new insight into how genes involved in these cellular processes
      may play a role in skeletal muscle growth and differentiation.

PMID- 12181368
TI  - Applications for multifrequency ultrasound biomicroscopy in mice from
      implantation to adulthood.
AB  - A new multifrequency (19-55 MHz) ultrasound biomicroscope with two-dimensional
      imaging and integrated Doppler ultrasound was evaluated using phantoms and
      isoflurane-anesthetized mice. Phantoms revealed the biomicroscope's lateral
      resolution was between 50 and 100 microm, whereas that of a conventional 13 MHz
      ultrasound system was 200-500 microm. This difference was apparent in the
      markedly higher resolution images achieved using the biomicroscope in vivo.
      Transcutaneous images of embryos in pregnant mice from approximately 2 days after
      implantation (7 days gestation) to near term (17.5 days) were obtained using
      frequencies from 25 to 40 MHz. The ectoplacental cone and early embryonic
      cavities were visible as were the placenta and embryonic organs throughout
      development to term. We also evaluated the ability of the biomicroscope to detect
      important features of heart development by examining embryos from 8.5 to 17.5 day
      gestation in exteriorized uteri using 55 MHz ultrasound. Cardiac looping,
      division of the outflow tract, and ventricular septation were visible. In
      postnatal imaging, we observed the heart and kidney of neonatal mice at 55 MHz,
      the carotid artery in juveniles (approximately 8 g body wt) and adults
      (approximately 25 g body wt) at 40 MHz, and the adult heart, aorta, and kidney at
      19 MHz. The coefficient of variation of carotid and aortic diameter measurements
      was 1-3%. In addition, blisters in GRIP1 -/- embryos and aortic valvular stenosis
      in two adults were readily visualized. Using image-guided Doppler function, low
      blood velocities in vessels as small as 100 microm in diameter including the
      primitive heart tube at day 8.5 were measurable, but high blood velocities (>37.5
      cm/s) such as in the heart and large arteries in late gestation and postnatal
      life were off-scale. Accurate cardiac dimension measurements were impeded by poor
      temporal resolution (4 frames/s). In summary, the multifrequency ultrasound
      biomicroscope is a versatile tool well suited to detailed study of the morphology
      of various organ systems throughout development in mice and for hemodynamic
      measurements in the low velocity range.

PMID- 12181369
TI  - Influenza vaccination.

PMID- 12181370
TI  - Influenza in working populations: an overview.

PMID- 12181371
TI  - The epidemiology of influenza.
AB  - Influenza remains a globally important cause of febrile respiratory illness.
      Influenza virus activity in the community results in significant mortality,
      morbidity and economic disruption, particularly in those at high risk of
      developing complications, such as the elderly and those with underlying chronic
      medical conditions, including pulmonary disease and diabetes mellitus. The
      occurrence in Hong Kong in 1997 of avian influenza H5N1 in man, which resulted in
      six deaths, served to remind us of the importance of continuing surveillance and
      preparation for the next pandemic.

PMID- 12181372
TI  - Nosocomial transmission of influenza.
AB  - Influenza is a common nosocomial infection. Serious outbreaks occur typically in
      elderly long-term patients, but have also been reported in renal, transplant and
      oncology units, neonatal intensive care and paediatrics. It is likely that staff
      patient cross-infection is common. Prompt diagnosis of an outbreak lies at the
      heart of an effective influenza control programme. This requires effective
      virological surveillance. There are a variety of strategies that can help to
      prevent spread of influenza in health care settings. Basic infection control
      should include isolating infected residents, restricting circulation of nursing
      staff between patients, and restriction of visitors. Annual influenza
      immunization should be offered to elderly patients, subjects with chronic
      disease, and those in long-term residential or nursing home care. Vaccination of
      health care workers has been shown to be effective in protecting elderly patients
      in long-term care. Use of oral amantadine or rimantadine is an additional
      possible strategy for prophylaxis or treatment during an outbreak.

PMID- 12181373
TI  - Influenza vaccines in adults.
AB  - Available influenza vaccines contain inactivated viruses, either whole or in
      parts, and are administered parenterally or intranasally. Their composition
      varies yearly because of viral antigenic shifts and drifts. Vaccines with a
      composition matching yearly World Health Organization recommendations are 72%
      [95% confidence interval (CI) = 54-83%] efficacious (prevention of influenza
      cases caused by influenza viruses A and B). Their effectiveness [capacity to
      prevent clinical influenza, or influenza-like illness (ILI)] is lower, at 37%
      (95% CI = 18-52%). A decision to vaccinate an adult population has to take into
      account the efficacy of the vaccines and their effectiveness (the likely
      proportion of ILI caused by influenza A and B viruses, amenable to prevention by
      vaccination), as well as costs and likely compliance. As the yearly levels of
      circulating A and B viruses are difficult to predict during the decision time for
      a vaccination campaign, there is a considerable element of uncertainty regarding
      the likely effectiveness of 'this year's' vaccine.

PMID- 12181374
TI  - The management of influenza in people of working age.
AB  - Influenza is common, causing considerable morbidity and sickness absence from
      work in most winters. Influenza vaccines have been available for >40 years, but
      are not extensively used in the workforce (in the UK). Amantadine has been
      available for 25 years as a treatment and prophylactic against influenza A
      infection, but has scarcely been used. In the last 3 years, two neuraminidase
      inhibitor antivirals, zanamivir and oseltamivir, have been introduced to the
      market for the treatment and prophylaxis of influenza A and B infections. This
      review focuses on aspects of prevention and treatment of influenza appropriate to
      people of working age. Decisions based on the cost-effectiveness of prevention
      and treatment options differ when viewed from the perspective of the healthcare
      provider, the employer or the employee. Options currently available need to be
      directed to a wider range of people than those conventionally regarded as the
      target risk group.

PMID- 12181375
TI  - Sickness absence due to influenza.
AB  - In addition to its recognized health effects, influenza has socio-economic
      consequences, most notably sickness absence and associated work disruption. It
      may account for 10-12% of all sickness absence from work. Data on the impact of
      influenza on work are limited. Most research has assessed the impact of an
      intervention, usually influenza immunization. Within the available literature,
      there are five randomized controlled trials in the workplace that have assessed
      the effectiveness of influenza immunization as an intervention: two in the
      general working population and three in the health sector. If the benefit desired
      is a reduction in sickness absence as a cost-effective measure, the likely
      outcome is a modest gain in years when incidence of influenza is increased in the
      community. There are some distinctive factors in the health care industry: health
      care workers may exhibit different absence behaviour, they may be more exposed to
      infection at work and they may pose a risk as a source of nosocomial infection.
      From the occupational health perspective, how do we best inform employers
      currently? The cost-effectiveness case has not been absolutely proven. More
      research appears necessary, including assessment of those factors that influence
      uptake of influenza immunization. In the interim, a targeted approach to certain
      job categories may be the way forward.

PMID- 12181376
TI  - A survey of the delivery and uptake of influenza vaccine among health care
      workers.
AB  - During the 1990s, policies for immunizing fit health care workers against
      influenza varied between National Health Service (NHS) employers and the uptake
      of influenza vaccine by NHS staff was poor. In light of recent Department of
      Health recommendations to immunize key health care staff against influenza, we
      explored the possible reasons for poor uptake and assessed the impact of an
      intensive promotion campaign on vaccine acceptance. Among 290 doctors and nurses,
      the main perceived barriers to influenza immunization were difficulty with
      practical access to vaccine and lack of time to attend. Following intensive
      promotion and improved local access to influenza vaccine, the uptake among health
      care workers was approximately doubled. However, the overall proportion of staff
      immunized was low (5%) and the immunization rate among medical staff was
      particularly poor (2%). The practical implications for influenza immunization
      campaigns aimed at health care workers are discussed.

PMID- 12181377
TI  - Vaccination against influenza: UK health care workers not on-message.
AB  - Vaccination of health care workers against influenza is considered to be
      important as a means of protecting patients from nosocomial infection. Vaccine
      uptake rates have been reported to be no more than 40% and often between 20 and
      30%. An evaluation of the performance of UK National Health Service trusts,
      following a governmental directive to implement vaccination during the winter of
      2000-2001, has shown a poor uptake of vaccine. Reasons for accepting or declining
      vaccine are discussed. There is a need for global leadership on this issue to
      promote the value of vaccination and to change the behaviour of health care
      workers.

PMID- 12181378
TI  - Reduced efficiency of influenza vaccine in prevention of influenza-like illness
      in working adults: a 7 month prospective survey in EDF Gaz de France employees,
      in Rhone-Alpes, 1996-1997.
AB  - The efficiency of influenza vaccine was evaluated in the working population by
      comparing the percentage of people presenting with an influenza-like illness
      (ILI) according to their influenza immunization status, drug expenses and
      workdays lost. A self-completed questionnaire about the vaccination was sent to
      5785 people randomly chosen among 18 249 workers. When any sick leave was
      incurred amongst the respondents (63.3%), of whom 301 were vaccinated and 3362
      unvaccinated, a clinical form was completed by the private physician and the
      medical adviser of the firm (Electricite de France and Gaz de France). A final
      self-completed questionnaire was sent to people whose sick leave was not
      documented by a physician's reported diagnosis. In total, we obtained complete
      data for 90.9% of the sampling. The vaccine coverage rate of 8.2% [95% confidence
      interval (95% CI) = 7.4-9.0%] was higher in men than in women, increasing with
      age and professional category. Among the 775 subjects with a medical diagnosis,
      the vaccine effectiveness was not significant: 27.3% (95% CI = -13.8 to 53.5%).
      In the unvaccinated group, 9.6% had days absent from work, versus 7.0% in the
      vaccinated group; the two populations were comparable in terms of clinical
      symptoms, smoking habits, exposure to respiratory risk factors and chronic
      pathology. The average duration of sick leave for ILI was not significantly
      different between vaccinated (0.5 days) and unvaccinated workers (0.6 days).
      Despite the large size of the population and the occurrence of an epidemic due to
      a virus closely related to the vaccine strain (A/Wuhan/359/95), the vaccine did
      not effectively protect the small vaccine group nor result in an economic
      benefit, whatever the professional group.

PMID- 12181379
TI  - Effect of glucose tolerance status on PAI-1 plasma levels in overweight and obese
      subjects.
AB  - OBJECTIVE: The aim of our study was to examine whether plasminogen activator
      inhibitor-1 (PAI-1) plasma levels varied as a function of differences in glucose
      tolerance status independently of body fatness, body-fat distribution, and
      insulin sensitivity. RESEARCH METHODS AND PROCEDURES: Plasma PAI-1 antigen
      levels, along with insulin resistance [measured by homeostatic model assessment
      (HOMA(IR))], central fat accumulation, body composition, blood pressure, and
      fasting concentrations of glucose, insulin, and lipids, were measured in 229
      overweight and obese [body mass index (BMI) > or =25 kg/m(2)) subjects with
      normal glucose tolerance (NGT) and in 44 age- and BMI-matched subjects with
      impaired glucose tolerance (IGT). RESULTS: Plasma PAI-1 antigen levels were
      significantly higher in IGT than in NGT subjects. Log PAI-1 was positively
      correlated with BMI, HOMA(IR), and log insulin, and inversely associated with
      high-density lipoprotein-cholesterol both in IGT and in NGT individuals. On the
      other hand, log PAI-1 was positively correlated with waist circumference, fat
      mass (FM), fat-free mass, systolic and diastolic blood pressure, and log
      triglycerides only in the NGT group. After multivariate analyses, the strongest
      determinants of PAI-1 levels were BMI, FM, waist circumference, and high-density
      lipoprotein cholesterol in the NGT group and only HOMA(IR) in the IGT cohort.
      DISCUSSION: This study demonstrates that PAI-1 concentrations are higher in IGT
      than in NGT subjects. Furthermore, we suggest that the influences of total
      adiposity, central fat, and insulin resistance, main determinants of PAI-1
      concentrations, are different according to the degree of glucose tolerance.

PMID- 12181380
TI  - Differences in resting metabolic rate between white and African-American young
      adults.
AB  - OBJECTIVE: A reported lower resting metabolic rate (RMR) in African-American
      women than in white women could explain the higher prevalence of obesity in the
      former group. Little information is available on RMR in African-American men.
      RESEARCH METHODS AND PROCEDURES: We assessed RMR by indirect calorimetry and body
      composition by DXA in 395 adults ages 28 to 40 years (100 African-American men,
      95 white men, 94 African-American women, and 106 white women), recruited from
      participants in the Coronary Artery Risk Development in Young Adults (CARDIA),
      Birmingham, Alabama, and Oakland, California, field centers. RESULTS: Using
      linear models, fat-free mass, fat mass, visceral fat, and age were significantly
      related to RMR, but the usual level of physical activity was not. After
      adjustment for these variables, mean RMR was significantly higher in whites
      (1665.07 +/- 10.78 kcal/d) than in African Americans (1585.05 +/- 11.02 kcal/d)
      by 80 +/- 16 kcal/d (p < 0.0001). The ethnic x gender interaction was not
      significant (p = 0.9512), indicating that the difference in RMR between African
      American and white subjects was similar for men and women. DISCUSSION: RMR is
      approximately 5% higher in white than in African-American participants in CARDIA.
      The difference was the same for men and women and for lean and obese individuals.
      The prevalence of obesity is not higher in African-American men than in white
      men. Because of these reasons, we believe that RMR differences are unlikely to be
      a primary explanation for why African-American women are more prone to obesity
      than white women.

PMID- 12181381
TI  - Genetic and environmental influences on body-fat measures among African-American
      twins.
AB  - OBJECTIVE: To investigate the genetic and environmental influences on body-fat
      measures including waist circumference (WC), waist-to-hip ratio (WHR), and body
      mass index (BMI) among African-American men and women. RESEARCH METHODS AND
      PROCEDURES: Measurements were taken as part of the Carolina African American Twin
      Study of Aging. This sample currently comprises 146 same-sex African-American
      twins with an average age of 50 years (range, 22 to 88 years). This analysis
      included 26 monozygotic and 29 dizygotic men and 45 monozygotic and 46 dizygotic
      women. Maximum likelihood quantitative genetic analysis was used. RESULTS: In
      men, additive genetic effects accounted for 77% of the variance in WC, 59% in
      WHR, and 89% in BMI. In women, additive genetic effects accounted for 76% of the
      variance in WC, 56% in WHR, and 73% in BMI. The remaining variance in both men
      and women was attributed to unique environmental effects (WC, 21%; WHR, 36%; BMI,
      11% in men and WC, 22%; WHR, 38%; BMI, 27% in women) and age (WC, 2%; WHR, 5% in
      men and WC, 2%; WHR, 6% in women). When BMI was controlled in the analysis of WC
      and WHR, it accounted for a portion of the genetic and environmental variance in
      WHR and over one-half of the genetic and environmental variance in WC.
      DISCUSSION: There are both genetic and environmental influences on WC, WHR, and
      BMI, and independent of BMI, there are genetic and environmental effects on WC
      and WHR among both genders. The results from this African-American twin sample
      are similar to findings among white twin samples.

PMID- 12181382
TI  - Body mass index and physical function in older women.
AB  - OBJECTIVE: We modified existing standardized measurement tools in the Physical
      Performance Test and tasks from the Frailty and Injuries: Cooperative Studies of
      Intervention Technique Study to evaluate physical function in older women. Our
      objectives were (1) to characterize physical function themes based on
      combinations of tasks (deriving factors or components) and (2) to quantify the
      correlation between derived factors and body mass index (BMI). RESEARCH METHODS
      AND PROCEDURES: Nutrition risk screens from enrollees in a Medicare-managed risk
      program served as the sampling frame. To obtain adequate representation for a
      range of BMI, a random sample was obtained of 90 women from the following BMI
      strata: BMI, 22 to <27 kg/m(2); BMI, 27 to <30 kg/m(2); and BMI, > or =30
      kg/m(2). Subjects were asked to perform a series of 18 functional tasks during a
      home visit. RESULTS: The mean age was similar in the three BMI groups with an
      overall mean age of 71 +/- 4.9 years (SD). Factors characterized by lower-body
      function, upper-body function, coordination, and strength were responsible for
      30%, 11%, 9%, and 9% of the variance in task scores, respectively. BMI,
      controlling for age, explained 5%, 14%, 3%, and 0% of the variation in these
      factors, respectively. Higher BMI is associated significantly with poorer upper-
      and lower-body function but is not associated significantly to strength or
      coordination. DISCUSSION: Higher BMI seems to differentially impede specific
      aspects of physical function, especially upper-body function, and to a lesser
      extent, lower-body function. BMI does not seem to be associated with levels of
      coordination or strength. Better understanding of how BMI impacts physical
      function will aid in the design of interventions to promote independent living in
      elderly, obese women.

PMID- 12181383
TI  - Health-related quality of life varies among obese subgroups.
AB  - OBJECTIVE: To compare the health-related quality of life (HRQOL) of
      overweight/obese individuals from different subgroups that vary in treatment
      seeking status and treatment intensity. RESEARCH METHODS AND PROCEDURES:
      Participants were from five distinct groups, representing a continuum of
      treatment intensity: overweight/obese community volunteers who were not enrolled
      in weight-loss treatment, clinical trial participants, outpatient weight-loss
      program/studies participants, participants in a day treatment program for
      obesity, and gastric bypass patients. The sample was large (n = 3353),
      geographically diverse (subjects were from 13 different states in the U.S.), and
      demographically diverse (age range, 18 to 90 years; at least 14% African
      Americans; 32.6% men). An obesity-specific instrument, the Impact of Weight on
      Quality of Life-Lite questionnaire, was used to assess health-related quality of
      life (HRQOL). RESULTS: Results indicated that obesity-specific HRQOL was
      significantly more impaired in the treatment-seeking groups than in the
      nontreatment-seeking group across comparable gender and body mass index (BMI)
      categories. Within the treatment groups, HRQOL varied by treatment intensity.
      Gastric bypass patients had the most impairment, followed by day treatment
      patients, followed by participants in outpatient weight-loss programs/studies,
      followed by participants in clinical trials. Obesity-specific HRQOL was more
      impaired for those with higher BMIs, whites, and women in certain treatment
      groups. DISCUSSION: There are differences in HRQOL across subgroups of
      overweight/obese individuals that vary by treatment-seeking status, treatment
      modality, gender, race, and BMI.

PMID- 12181384
TI  - Effects of obesity phenotype on coronary heart disease risk factors in response
      to weight loss.
AB  - OBJECTIVE: To determine whether there is a difference in risk-factor improvement
      for coronary heart disease (CHD) between the intra-abdominal fat (IF) and
      subcutaneous fat (SF) obesity phenotypes after weight loss. RESEARCH METHODS AND
      PROCEDURES: Subjects included 55 mildly obese women (body mass index, 25 to 36
      kg/m(2); age range, 34 to 63 years) who had at least two of three CHD risk
      factors [systolic blood pressure (SBP), >140 mm Hg; total cholesterol (TC), >220
      mg/dL; fasting plasma glucose, >110 mg/dL). Using computed tomography, IF obesity
      was classified as > or =110 cm(2) of the IF area measured; subjects with <110
      cm(2) were classified as having SF obesity. The IF and SF obesity groups were
      divided into diet-only and diet-plus-exercise groups. Assays and measurements
      were performed before and after a 14-week (98-day) intervention. RESULTS: Weight
      was reduced by 7 to 10 kg in each group. The IF and SF areas, SBP, diastolic
      blood pressure, TC, and low-density lipoprotein-cholesterol were significantly
      reduced in all groups (p < 0.01). Reduction in IF area was greater in IF obesity
      than in SF obesity, whereas no differences were observed in the improvement of
      CHD risk factors. Sample sizes needed for observing a significant difference for
      SBP, TC, triglycerides, and fasting plasma glucose were greater than the number
      of subjects in this study. DISCUSSION: Our results suggest that the influence of
      the obesity phenotype on improving CHD risk factors is not apparent. A larger
      study is needed to prove the validity of this finding.

PMID- 12181385
TI  - Influence of excess fat on cardiac morphology and function: study in
      uncomplicated obesity.
AB  - OBJECTIVE: To evaluate whether or not "uncomplicated" obesity (without associated
      comorbidities) is really associated with cardiac abnormalities. RESEARCH METHODS
      AND PROCEDURES: We evaluated cardiac parameters in obese subjects with long-term
      obesity, normal glucose tolerance, normal blood pressure, and regular plasma
      lipids. We selected 75 obese patients [body mass index (BMI) >30 kg/m(2)], who
      included 58 women and 17 men (mean age, 33.7 +/- 11.9 years; BMI, 37.8 +/- 5.5
      kg/m(2)) with a > or =10-year history of excess fat, and 60 age-matched normal
      weight controls, who included 47 women and 13 men (mean age, 32.7 +/- 10.4 years;
      BMI, 23.1 +/- 1.4 kg/m(2)). Each subject underwent an oral glucose tolerance test
      to exclude impaired glucose tolerance or diabetes mellitus, bioelectrical
      impedance analysis to calculate fat mass and fat-free mass, and echocardiography.
      RESULTS: Obese patients presented diastolic function impairment, hyperkinetic
      systole, and greater aortic root and left atrium compared with normal subjects.
      No statistically significant differences between obese subjects and normal
      subjects were found in indexed left ventricular mass (LVM/body surface area,
      LVM/height(2.7), and LVM/fat-free mass(kg)), and no changes in left ventricular
      geometry were observed. No statistically significant differences in cardiac
      parameters between extreme (BMI > 40 kg/m(2)) and mild obesity (BMI < 35 kg/m(2))
      were observed. DISCUSSION: In conclusion, our data showed that obesity, in the
      absence of glucose intolerance, hypertension, and dyslipidemia, seems to be
      associated only with an impairment of diastolic function and hyperkinetic
      systole, and not with left ventricular hypertrophy.

PMID- 12181386
TI  - Preferential stimulation of abdominal subcutaneous lipolysis after prednisolone
      exposure in humans.
AB  - OBJECTIVE: The role of cortisol in the regulation of lipolysis is not clear. This
      study was undertaken to explore whether a standard dose of prednisolone for 1
      week would influence lipolysis in abdominal and femoral tissue. RESEARCH METHODS
      AND PROCEDURES: We used the microdialysis technique, the forearm technique, and
      indirect calorimetry, in the fasting state, after 1 week of treatment with
      prednisolone (30 mg daily) or placebo. Eight healthy young men (age: 25 +/- 3
      years; height: 181 +/- 1 cm; body mass index [BMI]: 23.3 +/- 0.7 kg/m(2)) were
      studied. RESULTS: Treatment with prednisolone induced insulin resistance
      (Homeostasis Model Assessment index: placebo vs. prednisolone: 7.15 +/- 1.63 vs.
      17.00 +/- 14.26, p = 0.03), hyperinsulinemia (p = 0.01), and hyperglucagonemia (p
      = 0.001), whereas growth hormone concentrations were unaffected. Abdominal
      adipose tissue interstitial glycerol was increased during treatment with
      prednisolone in the face of significant hyperinsulinemia, although it barely
      reached statistical significance (p = 0.06). At the femoral adipose tissue depot,
      no difference in lipolysis was found. Arterial and venous free fatty acids (FFA)
      were comparable in the two situations, whereas the arteriovenous difference
      across the forearm was significantly decreased during treatment with
      prednisolone, indicating increased uptake, or decreased release of FFA. Energy
      expenditure (p = 0.3), respiratory quotient (p = 0.9), glucose oxidation (p =
      0.9), lipid oxidation (p = 1.0), and protein oxidation (p = 0.1) were unaltered
      on the 2 study days. DISCUSSION: Short-term treatment with a standard dose of
      corticosteroids induces increased abdominal adipose tissue lipolysis, as well as
      hyperinsulinemia, hyperglucagonemia, and insulin resistance.

PMID- 12181387
TI  - Role of ghrelin polymorphisms in obesity based on three different studies.
AB  - OBJECTIVE: Associations between preproghrelin DNA variants and obesity-related
      phenotypes were studied in 3004 subjects from the Quebec Family Study (QFS), the
      HERITAGE Family Study (HERITAGE), and the Swedish Obese Subjects (SOS) Study.
      RESEARCH METHODS AND PROCEDURES: Body mass index (BMI), fat mass (FM) from
      underwater weighing, and abdominal fat from computerized tomography were
      measured. The ghrelin polymorphisms were identified by polymerase chain reaction.
      RESULTS: Arg51Gln QFS subjects (n = 6) had lower ghrelin concentrations (p =
      0.007) than Arg51Arg subjects (n = 14). White preproghrelin Met72Met subjects in
      HERITAGE had the lowest BMI (p = 0.020), and those in the QFS cohort had the
      lowest FM (p < 0.001). Met72 carrier status (Met72+) was associated with lower FM
      (p = 0.026) and higher insulin-like growth factor-1 levels (p = 0.019) among
      blacks. Met72Met QFS subjects had less visceral fat (p = 0.002) and a lower
      fasting respiratory quotient (p = 0.037). HERITAGE Met72+ white subjects also
      showed lower exercise respiratory quotient (p = 0.030) and higher maximal oxygen
      uptake (p = 0.023). Furthermore, the prevalence of Met72+ was higher (19.2%; p <
      0.05) in SOS subjects whose BMI was < or =25 kg/m(2) than in those with BMI >25
      kg/m(2) (14.8%). SOS Met72+ obese women had a lower (11.4%; p = 0.032) prevalence
      of hypertension than noncarriers (23.9%). DISCUSSION: Arg51Gln mutation was
      associated with lower plasma ghrelin levels but not with obesity. The
      preproghrelin Met72 carrier status seems to be protective against fat
      accumulation and associated metabolic comorbidities.

PMID- 12181388
TI  - Predicting incident diabetes in Jamaica: the role of anthropometry.
AB  - OBJECTIVE: To evaluate the performance of the body mass index (BMI), waist
      circumference, waist-to-hip ratio (WHR), and waist-to-height ratio (WHTR) in
      predicting incident diabetes in Jamaica. RESEARCH METHODS AND PROCEDURES: A
      cohort of 728 nondiabetic adults (290 men and 438 women), ages 25 to 74 years and
      residents of Spanish Town, Jamaica, were followed for a mean of 4 years.
      Participants had fasting and 2-hour postchallenge glucose concentrations measured
      at baseline and follow-up. RESULTS: There were 51 cases of incident diabetes (17
      men and 34 women). All indices were independent predictors of diabetes, and none
      was clearly superior. The area under the receiver operating characteristics
      curves (95% confidence interval) for BMI was 0.74 (0.59 to 0.88) for men and 0.62
      (0.51 to 0.72) for women. For waist circumference, these values were 0.78 (0.65
      to 0.91) in men and 0.61 (0.50 to 0.71) in women. Similar results were obtained
      for WHR and WHTR. "Optimal" cut-off points for BMI were 24.8 kg/m(2) (men) and
      29.3 kg/m(2) (women). For waist circumference, these were 88 cm and 84.5 cm for
      men and women, respectively. Corresponding values for WHR were 0.87 and 0.80 and
      for WHTR were 0.51 and 0.54, respectively. DISCUSSION: Cut-off points for waist
      circumference and WHR were similar to those proposed in developed countries for
      women but lower in men. Waist circumference could be useful in health promotion
      as an alternative to BMI.

PMID- 12181389
TI  - Assessing the validity of body mass index standards in early postmenopausal
      women.
AB  - OBJECTIVE: To examine the relationship between percentage of total body fat
      (%Fat) and body mass index (BMI) in early postmenopausal women and to evaluate
      the validity of the BMI standards for obesity established by the NIH. RESEARCH
      METHODS AND PROCEDURES: Three hundred seventeen healthy, sedentary,
      postmenopausal women (ages, 40 to 66 years; BMI, 18 to 35 kg/m(2); 3 to 10 years
      postmenopausal) participated in the study. Height, weight, BMI, and %Fat, as
      assessed by DXA, were measured. Receiver operating characteristic analysis was
      performed to evaluate the ability of BMI to discriminate obesity from non-obesity
      using 38%Fat as the criterion value. RESULTS: A moderately high relationship was
      observed between BMI and %Fat (r = 0.81; y = 1.41x + 2.65) with a SE of estimate
      of 3.9%. Eighty-one percent of other studies examined fell within 1 SE of
      estimate as derived from our study. Receiver operating characteristic analysis
      showed that BMI is a good diagnostic test for obesity. The cutoff for BMI
      corresponding to the criterion value of 38%Fat that maximized the sum of the
      sensitivity and specificity was 24.9 kg/m(2). The true-positive (sensitivity) and
      false-positive (1--specificity) rates were 84.4% and 14.6%, respectively. The
      area under the curve estimate for BMI was 0.914. DISCUSSION: There is a strong
      association between %Fat and BMI in postmenopausal women. Current NIH BMI-based
      classifications for obesity may be misleading based on currently proposed %Fat
      standards. BMI >25 kg/m(2) rather than BMI >30 kg/m(2) may be superior for
      diagnosing obesity in postmenopausal women.

PMID- 12181390
TI  - Cross-sectional and longitudinal associations between body mass index and
      marriage-related factors.
AB  - OBJECTIVE: To assess the relationship between marriage and obesity. RESEARCH
      METHODS AND PROCEDURES: Cross-sectional and longitudinal associations were
      examined between participant body mass index (BMI), spouse BMI, and participant
      diet and exercise habits. RESULTS: Spouse and participant BMI and BMI changes
      over 2 years were significantly associated. Participant BMI was associated with
      higher consumption of calorie-dense foods and lower frequency of physical
      activity. Participants' eating and exercise habits were only weakly related to
      spouse BMI. BMI did not predict the likelihood of marriage or divorce. However,
      marriage was associated with a significant 2-year weight gain and divorce with a
      significant 2-year weight loss. DISCUSSION: The results suggest that spouse
      similarity in BMI is at least partly due to shared environment. The observed
      effects of marriage and divorce on weight may be due to the influence of marriage
      on inducements to eat (e.g., shared meals) or on motivation for weight control.

PMID- 12181391
TI  - Obesity affects nursing-care facility admission among whites but not blacks.
AB  - OBJECTIVE: This study examines whether obese individuals have a greater rate of
      nursing care facility admission than normal weight individuals. RESEARCH METHODS
      AND PROCEDURES: Data from the National Health and Nutrition Examination Survey
      Epidemiological Follow-up Survey were analyzed. Cox proportional hazards models
      were used to examine the relationship between baseline weight status and
      subsequent time to first nursing home admission while adjusting for sex, age,
      race, marital status, height, presence of children, smoking status, education,
      region, urban residence, income, and physical activity. RESULTS: Of 5960 adults
      45 to 74 years old, 989 individuals were admitted to a nursing care facility over
      the subsequent 20 years. Body mass index (BMI) was studied using five categories:
      < 18.5, 18.5 to <25, 25.0 to <30, 30.0 to <35, > or =35 kg/m(2). The effects of
      BMI differed by race: compared with those with a BMI of 18.5 to < 25 kg/m(2),
      adults with a BMI > or =30 kg/m(2) or a BMI <18.5 kg/m(2) had a greater rate of
      nursing home admission in whites, whereas no relationship was found in blacks.
      The inclusion of time to death with nursing home admission as a joint outcome
      yielded similar results. DISCUSSION: The large increase in the prevalence of
      obesity coupled with the rapid expansion of the number of older Americans will
      likely increase the demand for nursing facility use. More research is needed to
      understand differences in factors related to nursing home admission among ethnic
      groups.

PMID- 12181392
TI  - Use of the health and activities limitation index as a measure of quality of life
      in obesity.
AB  - OBJECTIVE: Obesity reduces the quality of life (QOL); however, quantification of
      obesity's impact on QOL is cumbersome. Utility indices reduce QOL measurements to
      a single numerical value that can be used in the calculation of Quality-Adjusted
      Life-Years and the cost effectiveness for obesity treatment. The purpose of this
      investigation is to assess the sensitivity of the Health and Activities
      Limitation Index (HALex) utility index to obesity. RESEARCH METHODS AND
      PROCEDURES: The answers to five questions regarding an individual's self
      perception of his or her health status and information about limitation in daily
      and work activities were collected from 32,440 adults in the 1998 National Health
      Information Survey. Answers to the questions were scored and converted to a
      utility index score ranging from 0 (near-death state) to 1 (perfect health) with
      no limitations. Average values for indices corresponding to differing body mass
      indices were obtained and significance determined by ANOVA. RESULTS: The utility
      index for normal weight males and females was 0.86 +/- 0.19 and fell to 0.68 +/-
      0.27 for superobese males and 0.60 +/- 0.28 in superobese females. Utility
      indices fell linearly with increasing body mass index and were lower for
      respondents having obesity-related comorbid conditions known to reduce the
      quality of life. DISCUSSION: There is a statistically significant decrease in the
      QOL with increasing obesity, slightly worse for women compared with men. The
      Health and Activities Limitation Index can quantitate the effect obesity and its
      complications have on quality of life.

PMID- 12181393
TI  - Immunomanipulation of appetite and body temperature through the functional
      mimicry of leptin.
AB  - OBJECTIVE: Although current obesity therapies produce some benefits, there is a
      need for new strategies to treat obesity. A novel proposal is the use of anti
      idiotypic antibodies as surrogate ligands or hormones. These anti-idiotypic
      antibodies carry an internal motif that imitates or mimics an epitope in the
      antigen (i.e., hormone or ligand). Thus, anti-idiotypic antibodies to several
      ligands may mimic them in transducing signals when binding to their receptors.
      RESEARCH METHODS AND PROCEDURES: We developed an anti-idiotypic polyclonal
      antibody against the region of a leptin monoclonal antibody that competitively
      binds leptin, mimicking the active site structure of leptin. To test whether our
      anti-idiotype could also reproduce leptin functions, we examined food intake,
      body weight, and colonic temperature in male Wistar rats (n = 9) in response to
      intracerebroventricular administration of the leptin anti-idiotype. RESULTS: Our
      leptin anti-idiotype induced a significant reduction in food intake coupled with
      an increase in body temperature comparable to that of leptin. That is, the
      intracerebroventricular administration of 8.0 microg of leptin anti-idiotype or
      5.0 microg leptin significantly increased colonic temperature (Delta 1.9 +/- 0.11
      degrees C and Delta 1.7 +/- 0.12 degrees C, respectively). In addition, both
      decreased 24-hour food intake (-26.4 +/- 2.4% and -21.9 +/- 2.2%) compared with
      the control. The gain in body weight was also decreased by acute administration
      of the anti-idiotype (-1.4 +/- 0.28%) and leptin (-1.1 +/- 0.17%) vs. the
      phosphate-buffered saline control (1.3 +/- 0.15%). DISCUSSION: These studies
      revealed that the leptin anti-idiotype inhibited food intake and enhanced heat
      production, mimicking leptin's central actions.

PMID- 12181394
TI  - Assessment of childhood obesity: national reference data or international
      approach?
AB  - Assessing body mass index in children requires cutoffs that are different from
      those for adults. The aim of this review is to summarize the evidence base,
      rationale, and practical issues that should inform decisions about the use of
      national and international reference data for assessing obesity in children. In
      many countries, decisions are being made without consideration of the existing
      evidence, and with limited understanding of the practical problems or potential
      harm that may arise.

PMID- 12181396
TI  - Health-related quality of life among obese subgroups.

PMID- 12181395
TI  - Effect of postpartum exercise on mothers and their offspring: a review of the
      literature.
AB  - Epidemiological studies suggest that childbearing may contribute to the
      development of obesity. In the past 12 years, several cross-sectional and
      randomized trials have addressed the effect of postpartum exercise on weight loss
      and/or energy balance in mostly lactating women. These studies suggest that
      moderate exercise without specific calorie restriction does not promote greater
      weight or fat loss. This may be because exercise may promote greater energy
      intake and/or reduced energy expenditure from nonexercise physical activity (thus
      preventing negative energy balance), but further research is needed. Regular
      exercise, however, is likely to have other important health benefits after
      childbirth. A few published studies suggest that postpartum exercise improves
      aerobic fitness, high-density lipoprotein-cholesterol levels, and insulin
      sensitivity. Exercise may also enhance psychological well-being, but controlled
      clinical studies are needed. Although two published studies have addressed
      whether exercise training attenuates lactation-induced bone loss, better
      controlled studies are needed to determine whether postpartum weight-bearing
      exercise can improve bone mineral density in lactating and nonlactating women
      alike. In lactating women, several studies have collectively determined that
      neither acute nor regular exercise has adverse effects on a mother's ability to
      successfully breast-feed. It needs to be determined whether a woman's
      participation in regular exercise after childbirth will improve her ability to
      mother or instill lifetime habits of regular physical activity in either herself
      or her offspring. Overall, published studies have established the importance of
      regular exercise during the postpartum period. More research, however, is needed
      in this important area.

PMID- 12181397
TI  - Leptin is a hypoxia-inducible gene.

PMID- 12181399
TI  - A molecular star in the wars against cancer.

PMID- 12181400
TI  - New strains of bacteria and exacerbations of chronic obstructive pulmonary
      disease.
AB  - BACKGROUND: The role of bacterial pathogens in acute exacerbations of chronic
      obstructive pulmonary disease is controversial. In older studies, the rates of
      isolation of bacterial pathogens from sputum were the same during acute
      exacerbations and during stable disease. However, these studies did not
      differentiate among strains within a bacterial species and therefore could not
      detect changes in strains over time. We hypothesized that the acquisition of a
      new strain of a pathogenic bacterial species is associated with exacerbation of
      chronic obstructive pulmonary disease. METHODS: We conducted a prospective study
      in which clinical information and sputum samples for culture were collected
      monthly and during exacerbations from 81 outpatients with chronic obstructive
      pulmonary disease. Molecular typing of sputum isolates of nonencapsulated
      Haemophilus influenzae, Moraxella catarrhalis, Streptococcus pneumoniae, and
      Pseudomonas aeruginosa was performed. RESULTS: Over a period of 56 months, the 81
      patients made a total of 1975 clinic visits, 374 of which were made during
      exacerbations (mean, 2.1 per patient per year). On the basis of molecular typing,
      an exacerbation was diagnosed at 33.0 percent of the clinic visits that involved
      isolation of a new strain of a bacterial pathogen, as compared with 15.4 percent
      of visits at which no new strain was isolated (P<0.001; relative risk of an
      exacerbation, 2.15; 95 percent confidence interval, 1.83 to 2.53). Isolation of a
      new strain of H. influenzae, M. catarrhalis, or S. pneumoniae was associated with
      a significantly increased risk of an exacerbation. CONCLUSIONS: The association
      between an exacerbation and the isolation of a new strain of a bacterial pathogen
      supports the causative role of bacteria in exacerbations of chronic obstructive
      pulmonary disease.

PMID- 12181401
TI  - Efficacy and safety of imatinib mesylate in advanced gastrointestinal stromal
      tumors.
AB  - BACKGROUND: Constitutive activation of KIT receptor tyrosine kinase is critical
      in the pathogenesis of gastrointestinal stromal tumors. Imatinib mesylate, a
      selective tyrosine kinase inhibitor, has been shown in preclinical models and
      preliminary clinical studies to have activity against such tumors. METHODS: We
      conducted an open-label, randomized, multicenter trial to evaluate the activity
      of imatinib in patients with advanced gastrointestinal stromal tumor. We assessed
      antitumor response and the safety and tolerability of the drug. Pharmacokinetics
      were assessed in a subgroup of patients. RESULTS: A total of 147 patients were
      randomly assigned to receive 400 mg or 600 mg of imatinib daily. Overall, 79
      patients (53.7 percent) had a partial response, 41 patients (27.9 percent) had
      stable disease, and for technical reasons, response could not be evaluated in 7
      patients (4.8 percent). No patient had a complete response to the treatment. The
      median duration of response had not been reached after a median follow-up of 24
      weeks after the onset of response. Early resistance to imatinib was noted in 20
      patients (13.6 percent). Therapy was well tolerated, although mild-to-moderate
      edema, diarrhea, and fatigue were common. Gastrointestinal or intraabdominal
      hemorrhage occurred in approximately 5 percent of patients. There were no
      significant differences in toxic effects or response between the two doses.
      Imatinib was well absorbed, with pharmacokinetics similar to those reported in
      patients with chronic myeloid leukemia. CONCLUSIONS: Imatinib induced a sustained
      objective response in more than half of patients with an advanced unresectable or
      metastatic gastrointestinal stromal tumor. Inhibition of the KIT signal
      transduction pathway is a promising treatment for advanced gastrointestinal
      stromal tumors, which resist conventional chemotherapy.

PMID- 12181402
TI  - Response to imatinib mesylate in patients with chronic myeloproliferative
      diseases with rearrangements of the platelet-derived growth factor receptor beta.
AB  - BACKGROUND: A small proportion of patients with chronic myeloproliferative
      diseases have constitutive activation of the gene for platelet-derived growth
      factor receptor beta (PDGFRB), which encodes a receptor tyrosine kinase. The gene
      is located on chromosome 5q33, and the activation is usually caused by a
      t(5;12)(q33;p13) translocation associated with an ETV6-PDGFRB fusion gene. The
      tyrosine kinase inhibitor imatinib mesylate specifically inhibits ABL, PDGFR, and
      KIT kinases and has impressive clinical efficacy in BCR-ABL-positive chronic
      myeloid leukemia. METHODS: We treated four patients who had chronic
      myeloproliferative diseases and chromosomal translocations involving 5q33 with
      imatinib mesylate (400 mg daily). Three of the four patients presented with
      leukocytosis and eosinophilia; their leukemia cells carried the ETV6-PDGFRB
      fusion gene. The fourth patient had leukocytosis, eosinophilia, and a t(5;12)
      translocation involving PDGFRB and an unknown partner gene; he also had extensive
      raised, ulcerated skin lesions that had been present for a long time. RESULTS: In
      all four patients, a normal blood count was achieved within four weeks after
      treatment began. In the patient with skin disease, the lesions began to resolve
      shortly after treatment began. The t(5;12) translocation was undetectable by 12
      weeks in three patients and by 36 weeks in the fourth patient. In the three
      patients with the ETV6-PDGFRB fusion gene, the transcript level decreased, and in
      one patient, it became undetectable by 36 weeks. All responses were durable at 9
      to 12 months of follow-up. CONCLUSIONS: Imatinib mesylate induces durable
      responses in patients with chronic myeloproliferative diseases associated with
      activation of PDGFRB.

PMID- 12181404
TI  - Images in clinical medicine. Pulmonary cryptococcal granulomas.

PMID- 12181403
TI  - Prospective study of polyomavirus type BK replication and nephropathy in renal
      transplant recipients.
AB  - BACKGROUND: Nephropathy associated with the polyomavirus type BK (BKV)
      nephropathy has emerged as a cause of allograft failure linked to
      immunosuppressive regimens containing tacrolimus or mycophenolate mofetil. The
      presence of viral inclusions, known as "decoy cells," in urine and the presence
      of BKV DNA in plasma have been proposed as markers for the replication of BKV and
      associated nephropathy, but data from prospective studies have been lacking.
      METHODS: In a prospective, single-center study, we followed 78 renal-transplant
      recipients who were receiving immunosuppressive therapy that included tacrolimus
      (37 patients) or mycophenolate mofetil (41 patients). Urine was tested for the
      presence of decoy cells at routine visits. BKV DNA was measured 3, 6, and 12
      months after transplantation and whenever decoy cells were detected. The viral
      load in plasma was quantified with the use of a real-time polymerase-chain
      reaction method. Renal biopsy was performed if allograft function deteriorated.
      RESULTS: Twenty-three patients had decoy-cell shedding a median of 16 weeks after
      transplantation (range, 2 to 69), 10 patients had BKV viremia at a median of 23
      weeks (range, 4 to 73), and 5 had BKV nephropathy at a median of 28 weeks (range,
      8 to 86). Kaplan-Meier estimates of the probability of decoy-cell shedding,
      viremia, and nephropathy were 30 percent (95 percent confidence interval, 20 to
      40 percent), 13 percent (95 percent confidence interval, 5 to 21 percent), and 8
      percent (95 percent confidence interval, 1 to 15 percent), respectively.
      Antirejection treatment, particularly with corticosteroids, was associated with
      BKV replication and nephropathy. The viral load in plasma was higher in patients
      with BKV nephropathy than in those without nephropathy (P<0.001 by the Mann
      Whitney test). BKV antibodies were detected in 77 percent of the 78 patients
      before transplantation, including 4 of 5 with BKV nephropathy. CONCLUSIONS: BKV
      nephropathy in renal-transplant recipients represents a secondary infection
      associated with rejection and its treatment in most cases and could be monitored
      by measuring the viral load in plasma.

PMID- 12181405
TI  - Clinical practice. Obstructive sleep apnea.

PMID- 12181406
TI  - Illness after international travel.

PMID- 12181407
TI  - Case records of the Massachusetts General Hospital. Weekly clinicopathological
      exercises. Case 25-2002. A 46-year-old woman with extensive pulmonary
      infiltrates.

PMID- 12181408
TI  - Bacteria and exacerbations of chronic obstructive pulmonary disease.

PMID- 12181409
TI  - BK virus nephropathy--polyomavirus adding insult to injury.

PMID- 12181410
TI  - n-3 fatty acids and the risk of sudden death.

PMID- 12181411
TI  - Treatment preferences of seriously ill patients.

PMID- 12181412
TI  - Hematogenous anaerobic osteomyelitis.

PMID- 12181413
TI  - Medical events during airline flights.

PMID- 12181414
TI  - Framework Convention on Tobacco Control.

PMID- 12181415
TI  - Transfusion medicine.

PMID- 12181416
TI  - Complete molecular remission in chronic myelogenous leukemia after imatinib
      therapy.

PMID- 12181417
TI  - Inhibition of tetrodotoxin (TTX)-resistant and TTX-sensitive neuronal Na(+)
      channels by the secretolytic ambroxol.
AB  - Ambroxol has a long history for the treatment of airway diseases because of its
      beneficial effects on surfactant synthesis and mucus-modifying properties. Some
      findings, however, point to an additional effect on neuronal signal transduction:
      ambroxol can suppress reflexes such as the cough or the corneal reflex. The
      airways and the cornea are innervated by C-fibers, which express voltage-gated
      Na(+) channels with and without sensitivity to tetrodotoxin (TTX). In this study,
      we performed voltage-clamp experiments to investigate whether ambroxol affects
      these channel types. In rat dorsal root ganglia, TTX-resistant Na(+) currents
      were suppressed in a concentration-dependent manner with IC(50) values of 35.2
      and 22.5 microM for tonic and phasic block, respectively. Depolarizing prepulses
      increased the potency of ambroxol, and steady-state inhibition curves were
      shifted to more negative values. The inhibition was not frequency-dependent. TTX
      sensitive currents were inhibited with lower potency (approximately 50%
      inhibition with 100 microM). Recombinant rat brain IIA channels in Chinese
      hamster ovary cells were blocked with IC(50) values of 111.5 and 57.6 microM for
      tonic and phasic block, respectively; in contrast to TTX-resistant channels the
      block was frequency-dependent. Thus, ambroxol indeed blocks neuronal voltage
      gated Na(+) channels, and TTX-resistant channels in sensory neurons were more
      sensitive than TTX-sensitive. Compared with known local anesthetics (e.g.,
      lidocaine or benzocaine), the potency for Na(+) channel block was relatively
      high. A recent clinical trial has further confirmed that ambroxol relieved pain
      and was beneficial in patients who suffered from sore throat.

PMID- 12181418
TI  - Development of a real-time in vivo transcription assay: application reveals
      pregnane X receptor-mediated induction of CYP3A4 by cancer chemotherapeutic
      agents.
AB  - We report the development of a rapid real-time assay that measures the
      transcription of luciferase reporter genes in transduced mouse hepatic cells in
      vivo. Luciferase activity is noninvasively measured by whole-body optical imaging
      within hours of the hydrodynamic injection of as little as 1 microg of naked DNA.
      Transcription of genes introduced as linearized DNA can be serially assayed for
      weeks in each animal. Transcription was quantified by extracorporal monitoring of
      bioluminescence as well as or better than by traditional in vitro bioluminescence
      assay. Our assay allows the measurement of transcription as it occurs, under the
      most informative biological conditions (i.e., in a living, intact organ).
      Furthermore, it substantially reduces the cost, time, and number of animals
      required for analysis of gene expression. The utility of the method is
      demonstrated in the discovery that topotecan and etoposide are ligands of
      pregnane X receptor that induce CYP3A4 transcription.

PMID- 12181419
TI  - Pharmacogenomics of human UDP-glucuronosyltransferases and irinotecan toxicity.

PMID- 12181420
TI  - Measures of efficacy using G proteins as endpoints: differential engagement of G
      proteins through single receptors.

PMID- 12181421
TI  - Depletion of intracellular GTP results in nuclear factor-kappaB activation and
      intercellular adhesion molecule-1 expression in human endothelial cells.
AB  - The expression of the intercellular adhesion molecule 1 (ICAM-1) on the surface
      of endothelial cells plays an important role in immune-mediated processes. The
      induction by the proinflammatory cytokine interleukin (IL)-1beta is regulated by
      nuclear transcription factor kappaB (NF-kappaB). We studied the effect of an
      inosine-5'-monophosphate dehydrogenase (IMPDH) inhibitor, mycophenolic acid
      (MPA), on constitutive and IL-1beta-induced expression of ICAM-1 in human
      umbilical vein endothelial cells (HUVECs). Unexpectedly, pretreatment with MPA
      enhanced the constitutive expression and potentiated the induction of ICAM-1 by
      IL-1beta, as detected by flow cytometry. Northern blot analysis revealed an
      increase in ICAM-1 mRNA levels in cells treated with MPA. This was associated
      with an increase in phosphorylation of IkappaB-alpha (an inhibitor of NF-kappaB),
      nuclear translocation of the NF-kappaB subunits p50 and p65 and their binding to
      DNA as detected by Western blotting, confocal microscopy, and electrophoretic
      mobility shift assay. The up-regulation of ICAM-1 by MPA was prevented by high
      doses (100 microM) of guanine or guanosine but not by physiological doses (0.1
      microM), indicating that guanylates are involved in endothelial responses to IL
      1beta. Cultivation of HUVECs in the absence of guanine enhanced further ICAM-1
      expression during IMPDH inhibition. These results demonstrate that cytokine
      mediated endothelial ICAM-1 expression can be modulated by IMPDH inhibition. We
      believe this represents a novel interaction between endothelial guanylate
      metabolism, NF-kappaB activation, and adhesion molecule expression.

PMID- 12181422
TI  - A77 1726 induces differentiation of human myeloid leukemia K562 cells by
      depletion of intracellular CTP pools.
AB  - A77 1726 (LEF) is the active metabolite of leflunomide, a recently approved
      immunosuppressive agent. We examined the ability of LEF to induce differentiation
      of a human erythroleukemia (K562) cell line and show that LEF induces a dose- and
      time-dependent differentiation of these cells as characterized by growth
      inhibition, hemoglobin production, and erythroid membrane protein glycophorin A
      expression. This effect was dependent on depletion of the intracellular
      pyrimidine ribonucleotides (UTP and CTP), and preceded by a specific S-phase
      arrest of the cell cycle. Supplementation of the cultures with exogenous uridine
      restored intracellular UTP and CTP to normal levels and prevented the LEF-induced
      cell cycle block and differentiation of K562 cells. Interestingly, addition of
      cytidine alone blocked the LEF-induced differentiation of K562 cells but only
      restored the CTP pool. By contrast, neither deoxycytidine nor thymidine prevented
      the effects of LEF on these cells. Similarly, pyrimidine starvation of a cell
      line lacking the de novo pyrimidine pathway (G9c) resulted in an S-phase arrest
      that was reversed by the addition of cytidine. Thus these studies demonstrate an
      important role for CTP in regulating cell cycle progression and show that LEF is
      an effective inducer of tumor cell differentiation through depletion of this
      ribonucleotide.

PMID- 12181423
TI  - Glutamate cascade to cAMP response element-binding protein phosphorylation in
      cultured striatal neurons through calcium-coupled group I metabotropic glutamate
      receptors.
AB  - Emerging evidence indicates that group I metabotropic glutamate receptors
      (mGluRs) play a significant role in the addictive plasticity of striatal neurons.
      The plasticity is probably mediated by altered cellular gene expression in
      relation to stimulation of group I mGluRs and associative signaling proteins. In
      this study, we investigated the signaling linkage of surface group I mGluRs to
      the nuclear transcription factor cAMP response element-binding protein (CREB) in
      cultured primary striatal neurons. We found that selective activation of group I
      mGluRs (primarily the mGluR5 subtype) was able to up-regulate CREB
      phosphorylation in neurochemically identified gamma-aminobutyratergic neurons but
      not glia. The CREB phosphorylation was independent of kainate/AMPA receptors but
      partially dependent of concomitant NMDA receptor activation. Because L-type
      voltage-operated Ca(2+) channel inhibitors substantially blocked the CREB
      phosphorylation, group I receptors are believed to lead to activation of L-type
      Ca(2+) channels, resulting in the CREB phosphorylation. Indeed, further studies
      on signaling pathways showed that group I mGluRs, by activating phospholipase C,
      induced a rapid and transient Ca(2+) release from the 1,4,5-triphosphate
      sensitive rather than ryanodine-sensitive Ca(2+) store. The transient Ca(2+) rise
      in turn triggered the opening of L-type Ca(2+) channels, resulting in a
      progressively larger increase in cytoplasmic Ca(2+) levels that is responsible
      for subsequent CREB phosphorylation. These results indicate that Ca(2+)-coupled
      group I mGluRs possess the ability to up-regulate CREB phosphorylation via the
      intracellular Ca(2+) release-induced activation of L-type Ca(2+) channels and, to
      a lesser extent, NMDA receptors in primary striatal neurons.

PMID- 12181424
TI  - Molecular cloning and characterization of the human voltage-gated calcium channel
      alpha(2)delta-4 subunit.
AB  - The voltage-gated calcium channel is composed of a pore-forming alpha(1) subunit
      and several regulatory subunits: alpha(2)delta, beta, and gamma. We report here
      the identification of a novel alpha(2)delta subunit, alpha(2)delta-4, from the
      expressed sequence tag database followed by its cloning and characterization. The
      novel alpha(2)delta-4 subunit gene contains 39 exons spanning about 130 kilobases
      and is co-localized with the CHCNA1C gene (alpha(1C) subunit) on human chromosome
      12p13.3. Alternative splicing of the alpha(2)delta-4 gene gives rise to four
      potential variants, a through d. The open reading frame of human alpha(2)delta-4a
      is composed of 3363 base pairs encoding a protein with 1120 residues and a
      calculated molecular mass of 126 kDa. The alpha(2)delta-4a subunit shares 30, 32,
      and 61% identity with the human calcium channel alpha(2)delta-1, alpha(2)delta-2,
      and alpha(2)delta-3 subunits, respectively. Primary sequence comparison suggests
      that alpha(2)delta-4 lacks the gabapentin binding motifs characterized for
      alpha(2)delta-1 and alpha(2)delta-2; this was confirmed by a [(3)H]gabapentin
      binding assay. In human embryonic kidney 293 cells, the alpha(2)delta-4 subunit
      associated with Ca(V)1.2 and beta(3) subunits and significantly increased
      Ca(V)1.2/beta(3)-mediated Ca(2+) influx. Immunohistochemical study revealed that
      the alpha(2)delta-4 subunit has limited distribution in special cell types of the
      pituitary, adrenal gland, colon, and fetal liver. Whether the alpha(2)delta-4
      subunit plays a distinct physiological role in select endocrine tissues remains
      to be demonstrated.

PMID- 12181425
TI  - Vascular smooth muscle cell phosphodiesterase (PDE) 3 and PDE4 activities and
      levels are regulated by cyclic AMP in vivo.
AB  - Prolonged incubation of several cell types, including cultured vascular smooth
      muscle cells (VSMC), with cyclic AMP-elevating agents increases cAMP
      phosphodiesterase (PDE) activity and levels. In this work, we describe for the
      first time an increase in arterial VSMC cAMP PDE activity and levels caused by
      cAMP-elevating agents when these agents are administered to rats in vivo.
      Injections of rats with dibutyryl cAMP (dbcAMP) or forskolin increased both PDE3
      and PDE4 activities in aortic and femoral artery VSMC. Consistent with the idea
      that cAMP-elevating agents increased PDE3 and PDE4 activities by acting directly
      on VSMC, local delivery of dbcAMP or forskolin to femoral arteries using a
      pluronic gel-based approach increased femoral artery VSMC PDE3 and PDE4
      activities to levels similar to those observed after injection of these agents.
      Consistent with a role for de novo mRNA and protein synthesis in the cAMP
      elevating agent induced increase in PDE3 and PDE4, 1) systemic administration of
      forskolin increased PDE3A, PDE3B, and PDE4D mRNA levels in aortic VSMC and
      femoral artery VSMC, 2) local delivery of dbcAMP increased PDE3A, PDE3B, and
      PDE4D3 protein levels in femoral artery VSMC, and 3) local administration of
      either actinomycin D or cycloheximide attenuated the effect of dbcAMP. In
      addition, our results indicate that the PDE3 and PDE4 variants increased by cAMP
      elevating agents in arterial VSMC in situ were distinct from those elevated by
      these agents in cultured arterial VSMC. Consistent with the effect of increased
      VSMC cAMP PDE on blood vessel function, inhibition of PDE3 and PDE4 activities
      potentiated the relaxant effect of forskolin in dbcAMP-treated femoral artery
      rings to a greater extent than in untreated control blood vessels. We propose
      that our findings are consistent with the concept that cAMP regulates VSMC cAMP
      PDE activity and levels in vivo and that VSMC phenotype influences the choice of
      cAMP PDE variant that is elevated. Our findings are discussed in the context that
      agents aimed at specific PDE3 or PDE4 variants could perhaps allow greater
      control of cAMP-mediated regulation of VSMC behaviors that are phenotype
      dependent.

PMID- 12181426
TI  - D2 and D3 dopamine receptor cell surface localization mediated by interaction
      with protein 4.1N.
AB  - We identified protein 4.1N as a D2-like dopamine receptor-interacting protein in
      a yeast two-hybrid screen. Protein 4.1N is a neuronally enriched member of the
      4.1 family of cytoskeletal proteins, which also includes protein 4.1R of
      erythrocytes and the 4.1G and 4.1B isoforms. The interaction of protein 4.1N was
      specific for the D2 and D3 dopamine receptors and was independently confirmed in
      pulldown and coimmunoprecipitation assays. Deletion mapping localized the site of
      dopamine receptor/protein 4.1N interaction to the N-terminal segment of the third
      intracellular domain of D2 and D3 receptors and the carboxyl-terminal domain of
      protein 4.1N. D2 and D3 receptors were also found to interact with the highly
      conserved carboxyl-terminal domain of proteins 4.1R, 4.1G, and 4.1B.
      Immunofluorescence studies show that protein 4.1N and D2 and D3 dopamine
      receptors are expressed at the plasma membrane of transfected human embryonic
      kidney 293 and mouse neuroblastoma Neuro2A cells. However, expression of D2 or D3
      receptors with a protein 4.1N truncation fragment reduces the level of D2 and D3
      receptor expression at the plasma membrane. These results suggest that protein
      4.1N/dopamine receptor interaction is required for localization or stability of
      dopamine receptors at the neuronal plasma membrane.

PMID- 12181427
TI  - Identification of interaction sites of cyclic nucleotide phosphodiesterase type
      3A with milrinone and cilostazol using molecular modeling and site-directed
      mutagenesis.
AB  - To identify amino acid residues involved in PDE3-selective inhibitor binding, we
      selected eight presumed interacting residues in the substrate-binding pocket of
      PDE3A using a model created on basis of homology to the PDE4B crystal structure.
      We changed the residues to alanine using site-directed mutagenesis technique,
      expressed the mutants in a baculovirus/Sf9 cell system, and analyzed the kinetic
      characteristics of inhibition of the mutant enzymes by milrinone and cilostazol,
      specific inhibitors of PDE3. The mutants displayed differential sensitivity to
      the inhibitors. Mutants Y751A, D950A, and F1004A had reduced sensitivity to
      milrinone (K(i) changed from 0.66 microM for the recombinant PDE3A to 7.5 to 156
      microM for the mutants), and diminished sensitivity to cilostazol (K(i) of the
      mutants were 18- to 371-fold higher than that of the recombinant PDE3A). In
      contrast, the mutants T844A, F972A and Q975A showed increased K(i) for cilostazol
      but no difference for milrinone from the recombinant PDE3A. Molecular models show
      that the PDE3 inhibitors cilostazol and milrinone share some of common residues
      but interact with distinct residues at the active site, suggesting that selective
      inhibitors can be designed with flexible size against PDE3 active site. Our study
      implies that highly conserved residuals Y751, D950 and F1004 in the PDE families
      are key residues for binding of both substrate and inhibitors, and nonconserved
      T844 may be responsible for the cilostazol selectivity of PDE3A. Detailed
      knowledge of the structure of inhibitory sites should contribute to development
      of more potent and specific inhibitory drugs.

PMID- 12181428
TI  - A fusion protein of the human P2Y(1) receptor and NTPDase1 exhibits functional
      activities of the native receptor and ectoenzyme and reduced signaling responses
      to endogenously released nucleotides.
AB  - To begin to address the functional interactions between constitutively released
      nucleotides, ectonucleotidase activity, and P2Y receptor-promoted signaling
      responses, we engineered the human P2Y(1) receptor in a fusion protein with a
      member of the ectonucleoside triphosphate diphosphohydrolase family, NTPDase1.
      Membranes prepared from Chinese hamster ovary (CHO)-K1 cells stably expressing
      either wild-type NTPDase1 or the P2Y(1) receptor-NTPDase1 fusion protein
      exhibited nucleotide-hydrolytic activities that were over 300-fold greater than
      activity measured in membranes from empty vector-transfected cells. The molecular
      ratio for nucleoside triphosphate versus diphosphate hydrolysis was approximately
      1:0.4 for both the wild-type NTPDase1 and P2Y(1)-NTPDase1 fusion protein. Stable
      expression of the P2Y(1)-NTPDase1 fusion protein conferred an ADP and 2MeSADP
      promoted Ca(2+) response to CHO-K1 cells. Moreover, the maximal capacity of the
      nonhydrolyzable agonist ADPbetaS to stimulate inositol phosphate accumulation was
      similar, and the EC(50) of ADPbetaS was lower in the fusion protein than the wild
      type receptor. In contrast, the substantial nucleotide-hydrolyzing activity of
      the fusion protein resulted in a greater than 50-fold shift to the right of the
      concentration-effect curve of ADP for activation of phospholipase C compared with
      the wild-type receptor. Heterologous expression of the P2Y(1) and other P2Y
      receptors results in marked increases in basal inositol phosphate levels. Given
      the high nucleotidase activity and apparently normal receptor signaling activity
      of the P2Y(1) receptor-NTPDase1 fusion protein, we quantitated basal inositol
      phosphate accumulation in cells stably expressing either the wild-type P2Y(1)
      receptor or the fusion protein. Although marked elevation of inositol phosphate
      levels occurred with wild-type P2Y(1) receptor expression, levels in cells
      expressing the fusion protein were not different from those in wild-type CHO-K1
      cells.

PMID- 12181430
TI  - Blockade of nitric-oxide synthase reduces choroidal neovascularization.
AB  - Nitric oxide (NO) promotes retinal and choroidal neovascularization, although
      different isoforms of nitric-oxide synthetase (NOS) are critical in each.
      Deficiency of endothelial NOS (eNOS) suppresses retinal but not choroidal
      neovascularization, whereas deficiency of neuronal NOS (nNOS) or inducible NOS
      (iNOS) suppresses choroidal, but not retinal neovascularization. In this study,
      we investigated the effect of N(G)-monomethyl-L-arginine (L-NMMA), a nonspecific
      NOS inhibitor, in three models of ocular neovascularization. Oral administration
      of L-NMMA caused significant inhibition of choroidal neovascularization in mice
      with laser-induced rupture of Bruch's membrane and significantly inhibited
      subretinal neovascularization in transgenic mice with expression of vascular
      endothelial growth factor (VEGF) in photoreceptors (rho/VEGF mice) but did not
      inhibit retinal neovascularization in mice with ischemic retinopathy. By
      extensive mating among mice deficient in NOS isoforms, triple homozygous mutant
      mice deficient in all three NOS isoforms were produced. These mice had marked
      suppression of choroidal neovascularization at sites of rupture of Bruch's
      membrane and near-complete suppression of subretinal neovascularization in
      rho/VEGF mice but showed no difference in ischemia-induced retinal
      neovascularization compared with wild-type mice. These data indicate that NO is
      an important stimulator of choroidal neovascularization and that reduction of NO
      by pharmacologic or genetic means is a good treatment strategy. However, the
      situation is more complex for ischemia-induced retinal neovascularization for
      which NO produced in endothelial cells by eNOS is stimulatory, but NO produced in
      other retinal cells by iNOS and/or nNOS is inhibitory. Selective inhibitors of
      eNOS may be needed for treatment of retinal neovascularization.

PMID- 12181429
TI  - Arsenic trioxide produces polymerization of microtubules and mitotic arrest
      before apoptosis in human tumor cell lines.
AB  - Arsenic trioxide (As(2)O(3)) has been found to induce apoptosis in leukemia cell
      lines and clinical remissions in patients with acute promyelocytic leukemia. In
      this study, we investigated the cytotoxic effect and mechanisms of action of
      As(2)O(3) in human tumor cell lines. As(2)O(3) caused inhibition of cell growth
      (IC(50) range, 3-14 microM) in a variety of human solid tumor cell lines,
      including four human non-small-cell lung cancer cell lines (H460, H322, H520,
      H661), two ovarian cancer cell lines (SK-OV-03, A2780), cervical cancer HeLa, and
      breast carcinoma MCF-7, as assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5
      diphenyltetrazolium bromide assay. Flow cytometry analysis showed that As(2)O(3)
      treatment resulted in a time-dependent accumulation of cells in the G(2)/M phase.
      We observed, using Wright-Giemsa and 4',6-diamidine-2-phenylindole
      dihydrochloride staining, that As(2)O(3) blocked the cell cycle in mitosis. In
      vitro examination revealed that As(2)O(3) markedly promoted tubulin
      polymerization without affecting GTP binding to beta-tubulin. Immunocytochemical
      and EM studies of treated MCF-7 cells showed that As(2)O(3) treatment caused
      changes in the cellular microtubule network and formation of polymerized
      microtubules. Similar to most anti-tubulin agents, As(2)O(3) treatment induced up
      regulation of the cyclin B1 levels and activation of p34(cdc2)/cyclinB1 kinase,
      as well as Bcl-2 phosphorylation. Furthermore, activation of caspase-3 and -7 and
      cleavage of poly(ADP-ribose) polymerase and beta-catenin occurred only in
      As(2)O(3)-induced mitotic cells, not in interphase cells, suggesting that
      As(2)O(3)-induced mitotic arrest may be a requirement for the activation of
      apoptotic pathways. In addition, As(2)O(3) exhibited similar inhibitory effects
      against parental MCF-7, P-glycoprotein-overexpressing MCF-7/doxorubicin cells,
      and multidrug resistance protein (MRP)-expressing MCF-7/etoposide cells
      (resistance indices, 2.3 and 1.9, respectively). Similarly, As(2)O(3) had similar
      inhibitory effect against parental ovarian carcinoma A2780 cells and tubulin
      mutation paclitaxel-resistant cell lines PTx10 and PTx22 (resistance indices,
      0.86 and 0.93, respectively), suggesting that its effect on tubulin
      polymerization and G(2)/M phase arrest is distinct from that of paclitaxel. Taken
      together, our data demonstrate that As(2)O(3) has a paclitaxel-like effect,
      markedly promotes tubulin polymerization, arrests cell cycle at mitosis, and
      induces apoptosis. In addition, As(2)O(3) is a poor substrate for transport by P
      glycoprotein and MRP, and non-cross-resistant with paclitaxel resistant cell
      lines due to tubulin mutation, suggesting that As(2)O(3) may be useful for
      treatment of human solid tumors, particularly in patients with paclitaxel
      resistance.

PMID- 12181431
TI  - Restoration of human beta-globin gene expression in murine and human IVS2-654
      thalassemic erythroid cells by free uptake of antisense oligonucleotides.
AB  - Correct human beta-globin mRNA has been restored in erythroid cells from
      transgenic mice carrying the human gene with beta-globin IVS2-654 splice mutation
      and from thalassemia patients with the IVS2-654/beta(E) genotype. This was
      accomplished in a dose- and time-dependent manner by free uptake of morpholino
      oligonucleotide antisense to the aberrant splice site at position 652 of intron 2
      in beta-globin pre-mRNA. Under optimal conditions of oligonucleotide uptake, the
      maximal levels of correct human beta-globin mRNA and hemoglobin A in patients'
      erythroid cells were 77 and 54%, respectively. These levels of correction were
      equal to, if not higher than, those obtained by syringe loading of the
      oligonucleotide into the cells. Comparison of splicing correction results with
      the cellular uptake of fluorescein-labeled oligonucleotide indicated that the
      levels of mRNA and hemoglobin A correlate well with the nuclear localization of
      the oligonucleotide and the degree of erythroid differentiation of cultured
      cells. Similar but not as pronounced results were obtained after the
      oligonucleotide treatment of bone marrow cells from IVS2-654 mouse. The
      effectiveness of the free antisense morpholino oligonucleotide in restoration of
      correct splicing of IVS2-654 pre-mRNA in cultured erythropoietic cells from
      transgenic mice and thalassemic patients suggests the applicability of this or
      similar compounds in in vivo experiments and possibly in treatment of
      thalassemia.

PMID- 12181432
TI  - Genistein inhibits cardiac L-type Ca(2+) channel activity by a tyrosine kinase
      independent mechanism.
AB  - It has been suggested that protein tyrosine kinase (PTK) activity can directly
      regulate cardiac L-type Ca(2+) channels. This conclusion is based to a large
      extent on the observation that the PTK inhibitor genistein can inhibit the
      cardiac L-type Ca(2+) current. The purpose of the present study was to determine
      whether the ability of genistein to inhibit cardiac L-type Ca(2+) channel
      activity is due to inhibition of PTK activity. Genistein significantly reduced
      the magnitude of the L-type Ca(2+) current in guinea pig ventricular myocytes
      recorded using the whole-cell patch-clamp technique. However, this effect was
      associated with extracellular, not intracellular, application of the drug.
      Peroxovanadate (PVN), a potent protein tyrosine phosphatase inhibitor, had no
      effect on the basal Ca(2+) current. PVN was also ineffective in preventing the
      inhibitory effect of genistein. Internal perfusion of cells with a pipette
      solution containing ATPgammaS was used to prevent reversibility of
      phosphorylation-dependent processes. This treatment did not alter the inhibitory
      effect of genistein, although it did result in irreversible protein kinase A
      dependent regulation of the Ca(2+) current. Bath application of lavendustin A, a
      PTK inhibitor that is structurally unrelated to genistein, did not affect the
      Ca(2+) current amplitude. The inhibitory effect of genistein was also associated
      with a hyperpolarizing shift in the voltage dependence of Ca(2+) channel
      inactivation. These results are consistent with the conclusion that the cardiac L
      type Ca(2+) current is not directly regulated by PTK activity and that the
      inhibitory effect of genistein is due to direct non-catalytic blockade of the
      channels.

PMID- 12181433
TI  - Effects of 5'-alkyl-benzothiadiazides on (R,S)-alpha-amino-3-hydroxy-5-methyl-4
      isoxazolepropionic acid (AMPA) receptor biophysics and synaptic responses.
AB  - Alkyl-substituted benzothiadiazides (BTDs) were tested for their effects on (R,S)
      alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)-type glutamate
      receptors. In excised patches, the 5'-ethyl derivative "D1" blocked the
      desensitization of AMPA receptor currents during prolonged application of
      glutamate (EC(50), 36 microM), and it slowed deactivation of responses elicited
      by 1-ms glutamate pulses greater than 10-fold. [(3)H]Fluorowillardiine binding to
      rat synaptic membranes was increased by D1 by a factor of 3.6 (EC(50), 17 microM)
      with a Hill coefficient near 2. In hippocampal slices, the compound reversibly
      increased excitatory postsynaptic currents and field excitatory postsynaptic
      potentials (EPSPs) with thresholds around 10 microM. The size of the alkyl
      substituent influenced both the potency and nature of the drug effect on synaptic
      currents: 5'-methyl compounds had a 2-fold greater effect on response amplitude
      than on response duration, whereas 5'-ethyl compounds like D1 caused greater
      increases in duration than amplitude. In tests with recombinantly expressed AMPA
      receptor subunits, D1 preferred the glutamate receptor (GluR) subunit GluR4 flip
      (0.64 microM) over GluR4 flop (5.3 microM); similar affinities but with smaller
      flip-flop differences were obtained for GluR1 through 3. These results show that
      D1 and congeners are significantly more potent than the parent compound IDRA-21
      and that they differ in two fundamental aspects from cyclothiazide, the most
      widely studied BTD: 1) D1 markedly increases the agonist affinity of AMPA
      receptors and 2) it has immediate and large effects on field EPSPs. The large
      gain in potency conferred by alkyl substitution suggests that the 5' substituent
      is in intimate contact with the receptor, with the size of the substituent
      determining the way in which receptor kinetics is changed.

PMID- 12181434
TI  - Differential activation of Gq/11 and Gi(3) proteins at 5-hydroxytryptamine(2C)
      receptors revealed by antibody capture assays: influence of receptor reserve and
      relationship to agonist-directed trafficking.
AB  - As determined by a guanosine 5'-O-(3-[(35)S]thio)triphosphate ([(35)S]GTPgammaS)
      binding assay, which does not distinguish G protein subtypes, 5-hydroxytryptamine
      (5-HT) and 2(S)- 1-(6-chloro-5-fluoro-1H-indol-1-yl)-2-propanamine fumarate
      (Ro600175) behaved as full agonists at human 5-HT(2C) (h5-HT(2C)) receptors (VSV
      isoform) stably expressed in Chinese hamster ovary (CHO) cells, whereas 1-2,5
      dimethoxy-4-iodophenyl-2-aminopropane (DOI), d-lysergic acid diethylamide (LSD),
      and lisuride exhibited partial agonist properties. After treatment with pertussis
      toxin to uncouple 5-HT(2C) receptors from Gi/Go but not Gq/11, DOI and LSD were
      as efficacious as 5-HT and Ro600175 in stimulating [(35)S]GTPgammaS binding,
      whereas lisuride still exhibited low efficacy (40%). Correspondingly, in a
      scintillation proximity assay employing specific antibodies against Gq/11, 5-HT,
      Ro600175, DOI, and LSD behaved as high-efficacy agonists, whereas lisuride showed
      efficacy of 36%. In contrast, when employing a specific antibody recognizing
      Gi(3), DOI and LSD were less efficacious (80 and 30%, respectively) than 5-HT and
      Ro600175, and lisuride was inactive. Agonist actions were specifically mediated
      by h5-HT(2C) receptors inasmuch as the selective 5-HT(2C) antagonist SB242,084
      blocked [(35)S]GTPgammaS binding at both Gq/11 and Gi(3). Agonist potency for
      stimulation of Gi(3) was ~6- to 8-fold less than for Gq/11, indicating that the
      latter was preferentially engaged by h5-HT(2C) receptors. Inactivation of h5
      HT(2C) receptors with the alkylating agent N-ethoxycarbonyl-2-ethoxy-1,2
      dihydroquinoline did not modify the efficacy of 5-HT, Ro600175, and DOI at Gq/11,
      whereas their efficacies were substantially reduced at Gi(3), indicating a
      greater receptor reserve for the former. Finally, the preferential activation of
      Gq/11 versus Gi(3) by DOI, LSD, and lisuride was diminished in the presence of
      lower receptor number. In conclusion, h5-HT(2C) receptors couple to both Gq/11
      and Gi(3) in CHO cells, and efficacy for G protein subtype activation is both
      ligand- and receptor reserve-dependent.

PMID- 12181435
TI  - Antibody capture assay reveals bell-shaped concentration-response isotherms for
      h5-HT(1A) receptor-mediated Galpha(i3) activation: conformational selection by
      high-efficacy agonists, and relationship to trafficking of receptor signaling.
AB  - Although serotonin 5-HT(1A) receptors couple to several Gi/o G-protein subtypes,
      little is known concerning their differential activation patterns. In this study,
      in membranes of Chinese hamster ovary cells expressing h5-hydroxytryptamine(1A)
      receptors (CHO-h5-HT(1A)), isotherms of 5-HT-stimulated guanosine-5'-O-(3
      [(35)S]thio)-triphosphate ([(35)S]GTPgammaS) binding were biphasic, suggesting
      coupling to multiple G-protein subtypes. The high potency component was abolished
      by preincubation with an antibody recognizing Galpha(i3) subunits and was
      resistant to induction of [(35)S]GTPgammaS dissociation by unlabeled GTPgammaS,
      thus yielding a bell-shaped concentration-response isotherm. To directly
      investigate Galpha(i3) activation, we adopted an antibody-capture/scintillation
      proximity assay. 5-HT and other high-efficacy agonists yielded bell-shaped
      [(35)S]GTPgammaS binding isotherms, with peaks at nanomolar concentrations. As
      drug concentrations increased, Galpha(i3) stimulation progressively returned to
      basal values. In contrast, the partial agonists (-)-pindolol and 4-(benzodioxan-5
      yl)1-(indan-2-yl)piperazine (S15535) displayed sigmoidal stimulation isotherms,
      whereas spiperone and other inverse agonists sigmoidally inhibited
      [(35)S]GTPgammaS binding. Agonist-induced stimulation and inverse agonist-induced
      inhibition of Galpha(i3) activation were i) abolished by pretreatment of CHO-h5
      HT(1A) cells with pertussis toxin; ii) reversed by the selective 5-HT(1A)
      antagonist (N-[2-[4-(2-methoxy-phenyl)-1-piperazinyl]ethyl]-N-(2-pyridinyl)
      cyclohexane-carboxamide) fumarate (WAY100,635), and iii) absent in nontransfected
      CHO cell membranes. 5-HT isotherms could be modified by altering sodium
      concentration; only stimulatory actions were observed at 300mM NaCl, whereas only
      inhibitory actions were seen at 10 mM NaCl. Furthermore, bell-shaped isotherms
      were not detected at short incubation times, suggesting time-dependent changes in
      receptor/Galpha(i3) coupling. Taken together, these data show that low but not
      high concentrations of high-efficacy 5-HT(1A) agonists direct receptor signaling
      to Galpha(i3). In contrast, partial agonists favor h5-HT(1A) receptor signaling
      to Galpha(i3) over a wide concentration range, whereas inverse agonists inhibit
      constitutive Galpha(i3) activation.

PMID- 12181436
TI  - Inhibitory effect of fluvastatin on lysophosphatidylcholine-induced nonselective
      cation current in Guinea pig ventricular myocytes.
AB  - Using the whole-cell voltage-clamp method, we investigated the effect of
      fluvastatin, a 3-hydroxy-3-methylglutaryl-CoA reductase inhibitor, on
      lysophosphatidylcholine (LPC)-induced nonselective cation current (I(NSC)) in
      guinea pig cardiac ventricular myocytes. External LPC (3 to approximately 50
      microM) induced I(NSC) in a dose-dependent manner with a lag. With fluvastatin (5
      microM) in the external solution, LPC induced I(NSC), which was significantly
      smaller and with a longer lag compared with that in the absence of fluvastatin.
      With mevalonic acid (MVA) (100 microM) in the external solution, fluvastatin did
      not diminish LPC-induced I(NSC). Geranylgeranylpyrophosphate, an MVA metabolite,
      in the pipette solution prevented fluvastatin from diminishing LPC-induced
      I(NSC), suggesting that isoprenylated signaling molecules, such as the small G
      protein Rho, might be involved in the LPC effect. Botulinum toxin C3, Rho-kinase
      inhibitor (R)-(+)-trans-N-(4-pyridyl)-4-(1-aminoethyl)-cyclohexanecarboxamide, 2
      HCl (Y-27632), or pertussis toxin in the pipette solution suppressed LPC-induced
      I(NSC). We conclude that LPC induces I(NSC) via a Gi/Go-coupled receptor and Rho
      mediated pathway. The inhibitory effect of fluvastatin on LPC-induced I(NSC)
      provides a new insight into the signal transduction mechanism and may have
      important clinical implications.

PMID- 12181437
TI  - Common human UGT1A polymorphisms and the altered metabolism of irinotecan active
      metabolite 7-ethyl-10-hydroxycamptothecin (SN-38).
AB  - 7-Ethyl-10-hydroxycamptothecin (SN-38) is the pharmacologically active metabolite
      of irinotecan, in addition to being responsible for severe toxicity.
      Glucuronidation is the main metabolic pathway of SN-38 and has been shown to
      protect against irinotecan-induced gastrointestinal toxicity. The purpose of this
      study was to determine whether common polymorphic UDP-glucuronosyltransferase
      (UGT) affects SN-38 glucuronidation. First, kinetic characterization of SN-38
      glucuronide (SN-38-G) formation was assessed for all known human UGT1A and UGT2B
      overexpressed in human embryonic kidney 293 cells. To assess the relative
      activity of UGT isoenzymes for SN-38, rates of formation of SN-38-G were
      monitored by liquid chromatography/mass spectrometry analysis and normalized by
      level of UGT cellular expression. Determination of intrinsic clearances predicts
      that hepatic UGT1A1 and UGT1A9 and the extrahepatic UGT1A7 are major components
      in SN-38-G formation, whereas a minor role is suggested for UGT1A6, UGT1A8, and
      UGT1A10. In support of the involvement of UGT1A9, a strong coefficient of
      correlation was observed in the glucuronidation of SN-38 and a substrate, mainly
      glucuronidate, by UGT1A9 (flavopiridol) by human liver microsomes (coefficient of
      correlation, 0.905; p = 0.002). In vitro functional experiments revealed a
      negative impact of the UGT1A1 allelic variants. Residual activities of 49, 7, 8,
      and 11% were observed for UGT1A1*6 (G(71)R), UGT1A1*27 (P(229)Q), UGT1A1*35
      (L(233)R), and UGT1A1*7 (Y(486)D), respectively. Common variants of UGT1A7,
      UGT1A7*3 (N(129)K;R(131)K;W(208)R), and UGT1A7*4 (W(208)R), displayed residual
      activities of 41 and 28% compared with the UGT1A7*1 allele. Taken together, these
      data provide the evidence that molecular determinants of irinotecan response may
      include the UGT1A polymorphisms studied herein and common genetic variants of the
      hepatic UGT1A9 isoenzyme yet to be described.

PMID- 12181438
TI  - A reevaluation of neuronal zinc measurements: artifacts associated with high
      intracellular dye concentration.
AB  - The emergence of zinc as a potent neurotoxin has prompted the development of
      techniques suitable for the measurement of intracellular free zinc ([Zn(2+)](i))
      in cultured cells. Accordingly, a new family of Zn(2+)-sensitive fluorophores has
      become available. Using ionophore-induced elevations of [Zn(2+)](i) in cultured
      neurons, we measured [Zn(2+)](i)-induced changes in the novel dyes FuraZin-1 and
      FluoZin-2 and compared them with the established [Zn(2+)](i)-sensitive
      fluorophores mag-fura-2 and Newport Green. All of these dyes effectively detected
      [Zn(2+)](i), and FuraZin-1, FluoZin-2, and Newport Green showed selectivity for
      [Zn(2+)](i) over [Ca(2+)](i) and [Mg(2+)](i). However, the dyes showed little
      difference in their apparent sensitivity to [Zn(2+)](i), even though their in
      vitro affinities for Zn(2+) varied from 20 nM to 3 microM. We show herein that
      this is a consequence of the relatively high concentrations of intracellular dye
      used in experiments of this nature. Thus, for the measurement of [Zn(2+)](i), the
      sensitivity of the reporting system is dominated by the intracellular dye
      concentration, whereas dye affinity is unimportant. We extend these findings to
      show that calibration of dye signal to ion concentration is critically dependent
      on precise measurement of intracellular dye concentration.

PMID- 12181439
TI  - Covalent binding of the nitroso metabolite of sulfamethoxazole leads to toxicity
      and major histocompatibility complex-restricted antigen presentation.
AB  - Treatment with sulfamethoxazole (SMX) can lead to hypersensitivity reactions. T
      cells from hypersensitive patients recognize either the parent drug and/or the
      reactive nitroso (SMX-NO) metabolite. In this study, using a novel in vitro rat
      splenocyte assay, we have investigated the toxicological and immunological
      consequences of cell surface haptenation by SMX-NO. SMX-NO was found to be
      unstable in solution; spontaneous transformation yielded appreciable amounts of
      SMX-hydroxylamine, nitro-SMX, and the previously unknown azoxy and azo dimers
      within 15 min. Irreversible binding of SMX-NO to cellular protein was
      demonstrated by flow cytometry, with haptenation being greater on the surface of
      antigen-presenting cells than on T cells. The consequences of irreversible
      binding of SMX-NO were examined in two ways. First, haptenation above a threshold
      level led to a proportionate increase in cell death (both apoptosis and
      necrosis). Indeed, the cells that became haptenated were the same as those that
      underwent necrotic cell death. Second, sensitized splenocytes proliferated in the
      presence of major histocompatibility complex (MHC)-restricted antigen derived
      from both viable and dead cells haptenated with low and high levels of SMX-NO,
      respectively. However, direct modification of MHC by SMX-NO was not the mechanism
      of antigen presentation. The antigenic threshold of SMX-NO for T-cell
      proliferation and toxicity was estimated to be between 0.5 and 1 microM and 5 to
      10 microM, respectively. The potential of SMX-NO to generate a potent antigen and
      cause cytotoxicity may in combination provide the signals necessary to induce a
      hypersensitivity reaction to SMX.

PMID- 12181440
TI  - Nuclear pregnane x receptor and constitutive androstane receptor regulate
      overlapping but distinct sets of genes involved in xenobiotic detoxification.
AB  - The nuclear pregnane X receptor (PXR) and constitutive androstane receptor (CAR)
      play central roles in protecting the body against environmental chemicals
      (xenobiotics). PXR and CAR are activated by a wide range of xenobiotics and
      regulate cytochrome P450 and other genes whose products are involved in the
      detoxification of these chemicals. In this report, we have used receptor
      selective agonists together with receptor-null mice to identify PXR and CAR
      target genes in the liver and small intestine. Our results demonstrate that PXR
      and CAR regulate overlapping but distinct sets of genes involved in all phases of
      xenobiotic metabolism, including oxidative metabolism, conjugation, and
      transport. Among the murine genes regulated by PXR were those encoding PXR and
      CAR. We provide evidence that PXR regulates a similar program of genes involved
      in xenobiotic metabolism in human liver. Among the genes regulated by PXR in
      primary human hepatocytes were the aryl hydrocarbon receptor and its target genes
      CYP1A1 and CYP1A2. These findings underscore the importance of these two nuclear
      receptors in defending the body against a broad array of potentially harmful
      xenobiotics.

PMID- 12181441
TI  - Neurotensin induces tyrosine hydroxylase gene activation through nitric oxide and
      protein kinase C signaling pathways.
AB  - The regulation of tyrosine hydroxylase (TH) represents an effective means to
      control the level of catecholamines, because TH is the major limiting enzyme of
      monoamine biosynthesis. The neuropeptide neurotensin (NT) is a neuromodulator of
      dopaminergic systems, and a direct interaction between NT and TH expression has
      been demonstrated in vivo and in vitro. In the present work, the molecular
      mechanisms and signaling pathways responsible for TH gene activation have been
      explored. In N1E-115 cells, NT agonist induced a TH protein level increase,
      correlating with a significant increase in TH mRNA abundance. This cellular
      response was the result of TH promoter activation, via c-fos and Jun D binding at
      the AP-1 responsive element. Using selective protein kinase C and nitric oxide
      synthase inhibitors, we demonstrate, by quantitative reverse transcription
      polymerase chain reaction, gel shift, and protein assays, that TH gene activation
      by NT agonist requires both protein kinase C stimulation and nitric oxide
      production. The two pathways exert distinct roles; whereas nitric oxide synthase
      inhibitors blocked c-fos expression, protein kinase C inhibitors blocked that of
      Jun D. The requirement for two distinct and concomitant pathways by NT
      demonstrates a very fine level of control of specificity on TH gene activation.

PMID- 12181442
TI  - Characterization and comparison of RGS2 and RGS4 as GTPase-activating proteins
      for m2 muscarinic receptor-stimulated G(i).
AB  - RGS2 and RGS4 were studied for their effects as GTPase activating proteins (GAPs)
      on receptor-activated G(i) in a novel steady-state assay using membranes from Sf9
      cells quadruply infected with baculoviruses encoding the m2 muscarinic receptor,
      G(alphai2), G(beta1), and G(gamma2). In the presence of the muscarinic agonist
      carbachol, regulator of G protein signaling 2 (RGS2) and RGS4 each produced up to
      a 10-fold increase in agonist-dependent GTPase activity. The observed K(m) for
      GTP in this system was increased in the presence of RGS4. NaCl and KCl inhibited
      the GAP activities of both RGS2 and RGS4, although they had no effect on GTPase
      activity in the absence of RGS proteins. MgCl(2) had a complex effect on GTPase
      activity, with optimal RGS2 and RGS4 GAP activities occurring, respectively, at
      high micromolar and low millimolar concentrations of free Mg(2+). The
      concentration dependence of RGS GAP activity was assessed, and RGS4 was found to
      be more potent than RGS2 by up to an order of magnitude. This direct observation
      confirms a similar difference in potency found when these two RGS proteins were
      compared for their ability to inhibit signaling downstream of G(i). RGS2 yielded
      Hill coefficients greater than 2.0, suggesting that it may bind in a positively
      cooperative manner to oligomeric structures containing more than one G protein.
      Furthermore, RGS4 yielded a bell-shaped dose-dependence under low magnesium (0.5
      mM) conditions, which is also consistent with the idea of RGS cooperativity.

PMID- 12181443
TI  - Akt activation induced by lysophosphatidic acid and sphingosine-1-phosphate
      requires both mitogen-activated protein kinase kinase and p38 mitogen-activated
      protein kinase and is cell-line specific.
AB  - The signaling pathways that lysophosphatidic acid (LPA) and sphingosine-1
      phosphate (S1P) use to activate Akt in ovarian cancer cells are investigated
      here. We show for the first time, with the use of both pharmacological and
      genetic inhibitors, that the kinase activity and S473 phosphorylation of Akt
      induced by LPA and S1P requires both mitogen-activated protein (MAP) kinase
      kinase (MEK) and p38 MAP kinase, and MEK is likely to be upstream of p38, in HEY
      ovarian cancer cells. The requirement for both MEK and p38 is cell type- and
      stimulus-specific. Among 12 cell lines that we tested, 11 respond to LPA and S1P
      and all of the responsive cell lines require p38 but only nine of them require
      MEK. Among different stimuli tested, platelet-derived growth factor stimulates
      S473 phosphorylation of Akt in a MEK- and p38-dependent manner. However,
      epidermal growth factor, thrombin, and endothelin-1-stimulated Akt S473
      phosphorylation require p38 but not MEK. Insulin, on the other hand, stimulates
      Akt S473 phosphorylation independent of both MEK and p38 in HEY cells. T308
      phosphorylation stimulated by LPA/S1P requires MEK but not p38 activation. MEK
      and p38 activation were sufficient for Akt S473 but not T308 phosphorylation in
      HEY cells. In contrast to S1P and PDGF, LPA requires Rho for Akt S473
      phosphorylation, and Rho is upstream of phosphatidylinositol 3-kinase (PI3-K).
      LPA/S1P-induced Akt activation may be involved in cell survival, because LPA and
      S1P treatment in HEY ovarian cancer cells results in a decrease in paclitaxel
      induced caspase-3 activity in a PI3-K/MEK/p38-dependent manner.

PMID- 12181444
TI  - Activation of phospholipase Cgamma2 by tyrosine phosphorylation.
AB  - Phospholipase Cgamma2 (PLCgamma2) has been implicated in collagen-induced signal
      transduction in platelets and antigen-dependent signaling in B-lymphocytes. It
      has been suggested that tyrosine kinases activate PLCgamma2. We expressed the
      full-length cDNA for human PLCgamma2 in bacteria and purified the recombinant
      enzyme. The recombinant enzyme was Ca(2+)-dependent with optimal activity in the
      range of 1 to 10 microM Ca(2+). In vitro phosphorylation experiments with
      recombinant PLCgamma2 and recombinant Lck, Fyn, and Lyn tyrosine kinases showed
      that phosphorylation of PLCgamma2 led to activation of the recombinant enzyme.
      Using site-directed mutagenesis, we investigated the role of specific tyrosine
      residues in activation of PLCgamma2. A mutant form of PLCgamma2, in which all
      three tyrosines at positions 743, 753, and 759 in the SH2-SH3 linker region were
      replaced by phenylalanines, exhibited decreased Lck-induced phosphorylation and
      completely abolished the Lck-dependent activation of PLCgamma2. Individual
      mutations of these tyrosine residues demonstrated that tyrosines 753 and 759, but
      not 743, were responsible for Lck-induced activation of PLCgamma2. To confirm
      these results, we procured a phosphospecific antibody to a peptide containing
      phosphorylated tyrosines corresponding to residues 753 and 759. This antibody
      recognized phosphorylated wild-type PLCgamma2 on Western blots but did not
      interact with unphosphorylated PLCgamma2 or with PLCgamma2 containing mutated
      tyrosine residues at 753 and 759. Using this antibody, we showed in intact
      platelets that collagen, a PLCgamma2-dependent agonist, induces phosphorylation
      of PLCgamma2 at Y753 and Y759. These studies demonstrate the importance of these
      two tyrosine residues in regulating the activity of PLCgamma2.

PMID- 12181445
TI  - Inhibition of cyclin-dependent kinase 2 by the Chk1-Cdc25A pathway during the S
      phase checkpoint activated by fludarabine: dysregulation by 7
      hydroxystaurosporine.
AB  - Human myeloid leukemia ML-1 cells responded to cytostatic concentrations of
      fludarabine nucleoside (F-ara-A) by instituting an arrest in S-phase that
      involved the inhibition of cyclin-dependent kinase 2 (Cdk2). This seemed to be
      mediated by 1) persistent phosphorylation on the Tyr(15) residue of Cdk2 and 2)
      an increased association of Cdk2 with p21. S-phase arrest was also associated
      with an increase in Chk1 kinase activity. Concomitantly, the activity of Cdc25A
      phosphatase was decreased. Immunoprecipitation studies demonstrated complexes of
      Cdk2, Cdc25A, and Chk1. The addition of the Chk1 kinase inhibitor 7
      hydroxystaurosporine (UCN-01) to F-ara-A-arrested S-phase cells resulted in a
      rapid decrease in the fraction of cells with an S-phase DNA content and a
      corresponding increase in the fraction of apoptotic cells. Under these
      conditions, the kinase activity of Chk1 was reduced, Cdc25A phosphatase activity
      was increased, the level of Tyr(15) phosphorylation of Cdk2 was reduced, and the
      kinase activity associated with immunoprecipitates of Cdk2 and cyclin A was
      reactivated. UCN-01 also had no effect on the association of p21 with Cdk2.
      Lastly, cells incubated with UCN-01 before F-ara-A addition did not arrest in S
      phase. Thus, the DNA damage induced by F-ara-A initiated a hierarchical
      regulatory cascade through Chk1 and Cdc25A that resulted in Cdk2 inhibition,
      affecting an S-phase checkpoint that was dysregulated by UCN-01. These results
      suggest a mechanism by which UCN-01 enhances the cytotoxicity of agents that
      cause an S-phase arrest.

PMID- 12181446
TI  - Regulation of platinum-compound cytotoxicity by the c-Jun N-terminal kinase and c
      Jun signaling pathway in small-cell lung cancer cells.
AB  - Cytotoxic platinum compounds including cisplatin are standard cancer
      chemotherapeutics and are also activators of stress-signaling pathways. In this
      study, we tested the role of the c-Jun N-terminal kinase (JNK) family of mitogen
      activated protein kinases and their transcription factor target, c-Jun, in the
      cytotoxic response of small-cell lung cancer (SCLC) cells to cisplatin and its
      less effective trans-isomer, transplatin. Both agents stimulated JNK activity;
      the transplatin response was rapid and transient, whereas JNK activation by
      cisplatin was delayed and sustained. Despite the differential kinetics of JNK
      activation, expression of nonphosphorylatable JNK mutants sensitized the SCLC
      cells to killing by cisplatin or transplatin, suggesting that JNK activation in
      response to these agents signals a protective response. Consistent with this
      finding, overexpression of the JNK target, c-Jun, significantly protected SCLC
      cells from platinum compounds, whereas expression of a c-Jun mutant encoding only
      the DNA binding domain increased the sensitivity of the SCLC cells to these
      drugs. These findings support the hypothesis that activation of the JNKs by
      platinum compounds controls c-Jun-dependent transcriptional events that promote a
      protective response in SCLC cells. Oligonucleotide array analysis identified
      genes encoding a variety of signaling proteins whose expression was reciprocally
      changed by c-Jun and c-Jun-DBD (c-Jun-DNA binding domain). It is noteworthy that
      genes whose products are involved in DNA repair, glutathione synthesis, or drug
      accumulation did not exhibit altered expression by c-Jun or c-Jun-DBD. The
      findings indicate that inhibition of the JNK pathway is a potential means to
      enhance the sensitivity of SCLC cells to platinum compounds.

PMID- 12181447
TI  - Dexamethasone inhibits inducible nitric-oxide synthase expression and nitric
      oxide production by destabilizing mRNA in lipopolysaccharide-treated macrophages.
AB  - Nitric oxide (NO) production through the inducible nitric-oxide synthase (iNOS)
      pathway is increased in inflammatory diseases and leads to cellular injury. Anti
      inflammatory steroids inhibit the expression of various inflammatory genes,
      including iNOS. In the present study, we investigated the mechanism how
      dexamethasone decreased NO production in murine J774 macrophages. Dexamethasone
      (0.1-10 microM) inhibited the production of NO and iNOS protein in a dose
      dependent manner in cells stimulated with lipopolysaccharides (LPS). In contrast,
      in cells treated with a combination of LPS and interferon-gamma (IFN-gamma),
      dexamethasone did not reduce iNOS expression and NO formation. Dissociated
      glucocorticoid RU24858 inhibited iNOS expression and NO production to levels
      comparable with that of dexamethasone, suggesting that the reduced iNOS
      expression by dexamethasone is not a GRE-mediated event. In further studies, the
      effect of dexamethasone on iNOS mRNA levels was tested by actinomycin assay. The
      half-life of iNOS mRNA after LPS treatment was 5 h 40 min, and dexamethasone
      reduced it to 3 h. The increased degradation of iNOS mRNA was reversed by a
      protein synthesis inhibitor cycloheximide. iNOS mRNA was more stabile in cells
      treated with a combination of LPS plus IFN-gamma (half-life = 8 h 20 min), and
      dexamethasone had a minor effect in these conditions. In conclusion,
      dexamethasone decreases iNOS-dependent NO production by destabilizing iNOS mRNA
      in LPS-treated cells by a mechanism that requires de novo protein synthesis.
      Also, decreased iNOS mRNA and protein expression and NO formation by
      dexamethasone was not found in cells treated with a combination of LPS plus IFN
      gamma, suggesting that the effect of dexamethasone is stimulus-dependent.

PMID- 12181448
TI  - Mechanisms underlying tissue selectivity of anandamide and other vanilloid
      receptor agonists.
AB  - Anandamide acts as a full vanilloid receptor agonist in many bioassay systems,
      but it is a weak activator of primary afferents in the airways. To address this
      discrepancy, we compared the effect of different vanilloid receptor agonists in
      isolated airways and mesenteric arteries of guinea pig using preparations
      containing different phenotypes of the capsaicin-sensitive sensory nerve. We
      found that anandamide is a powerful vasodilator of mesenteric arteries but a weak
      constrictor of main bronchi. These effects of anandamide are mediated by
      vanilloid receptors on primary afferents and do not involve cannabinoid
      receptors. Anandamide also contracts isolated lung strips, an effect caused by
      the hydrolysis of anandamide and subsequent formation of cyclooxygenase products.
      Although capsaicin is equally potent in bronchi and mesenteric arteries,
      anandamide, resiniferatoxin, and particularly olvanil are significantly less
      potent in bronchi. Competition experiments with the vanilloid receptor antagonist
      capsazepine did not provide evidence of vanilloid receptor heterogeneity.
      Arachidonoyl-5-methoxytryptamine (VDM13), an inhibitor of the anandamide membrane
      transporter, attenuates responses to olvanil and anandamide, but not capsaicin
      and resiniferatoxin, in mesenteric arteries. VDM13 did not affect responses to
      these agonists in bronchi, suggesting that the anandamide membrane transporter is
      absent in this phenotype of the sensory nerve. Computer simulations using an
      operational model of agonism were consistent, with differences in intrinsic
      efficacy and receptor content being responsible for the remaining differences in
      agonist potency between the tissues. This study describes differences between
      vanilloid receptor agonists regarding tissue selectivity and provides a
      conceptual framework for developing tissue-selective vanilloid receptor agonists
      devoid of bronchoconstrictor activity.

PMID- 12181449
TI  - Role of the human herpesvirus 6 u69-encoded kinase in the phosphorylation of
      ganciclovir.
AB  - The human herpesvirus 6 (HHV-6) U69 gene product (pU69) is the presumed
      functional homolog of the human cytomegalovirus (HCMV) UL97-encoded kinase
      (pUL97), which converts ganciclovir to its monophosphate metabolite in HCMV
      infected cells. It has been reported that insertion of U69 into baculovirus
      confers sensitivity to ganciclovir in insect cells (J Virol 73:3284-3291, 1999).
      Our metabolic studies in HHV-6-infected human T-lymphoblast cells indicated that
      the efficiency of ganciclovir phosphorylation induced by HHV-6 was relatively
      poor. Recombinant vaccinia viruses (rVVs), expressing high levels of pU69 from
      two HHV-6 strains (representing the A and B variant), were constructed and used
      to compare the ganciclovir-phosphorylating capacity of pU69 and pUL97 in human
      cells. Metabolic studies with [8-(3)H]ganciclovir showed that ganciclovir was
      phosphorylated in human cells infected with pU69-expressing rVVs, although the
      levels of phosphorylated ganciclovir metabolites were approximately 10-fold lower
      than those observed with pUL97. We also demonstrated that pU69, like pUL97, is
      expressed as a nuclear protein. Our results indicate that the limited
      phosphorylation of ganciclovir by pU69 may contribute to its modest antiviral
      activity against HHV-6 in certain cell systems.

PMID- 12181450
TI  - 2,3,7,8-Tetrachlorodibenzo-p-dioxin suppresses tumor necrosis factor-alpha and
      anti-CD40-induced activation of NF-kappaB/Rel in dendritic cells: p50 homodimer
      activation is not affected.
AB  - 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) suppresses many immune responses, both
      innate and adaptive. Suppression is mediated by the aryl hydrocarbon receptor
      (AhR), a ligand-activated transcription factor. The AhR mediates TCDD toxicity
      presumably through the alteration of transcriptional events, either by promoting
      gene expression or potentially by physically interacting with other transcription
      factors. Another transcription factor, NF-kappaB/Rel, is involved in several
      signaling pathways in immune cells and is crucial for generating effective immune
      responses. Dendritic cells (DCs), considered to be the "pacemakers" of the immune
      system, were recently recognized as targets of TCDD and are also dependent on NF
      kappaB/Rel for activation and survival. In these studies, we investigated whether
      TCDD would alter the activation of NF-kappaB/Rel in DCs. The dendritic cell line
      DC2.4 was exposed to TCDD before treatment with tumor necrosis factor alpha (TNF
      alpha) or anti-CD40, and NF-kappaB/Rel activation was measured by electrophoretic
      mobility shift assay and immunoblotting. TCDD suppressed the binding of NF
      kappaB/Rel to its cognate response element in TNF-alpha- and anti-CD40-treated
      cells and blocked translocation to the nucleus. The AhR was shown to associate
      with RelA, after coimmunoprecipitation, and seemed to block its binding to DNA.
      It is noteworthy that p50 homodimers freely bound to DNA. These results suggest
      that TCDD may alter the balance between NF-kappaB/Rel heterodimers and
      transcriptional inhibitory p50 homodimers in DCs, leading to defects in the DCs
      and suppression of the immune response.

PMID- 12181452
TI  - Regulation of human CYP2C9 by the constitutive androstane receptor: discovery of
      a new distal binding site.
AB  - The CYP2C subfamily metabolizes many clinically important drugs. These genes
      respond to prototypical inducers such as phenobarbital and rifampicin, yet little
      has been reported on the mechanisms of induction. This report examines the
      regulation of CYP2C9 with respect to two specific receptors thought to be
      involved in phenobarbital (PB) induction, the constitutive androstane receptor
      (CAR) and pregnane X receptor (PXR). Transfection of either mouse CAR (mCAR) or
      human CAR (hCAR) into HepG2 cells results in increased CYP2C9 mRNA content.
      Inducers further increased this response in CAR transfected cells. mCAR but not
      hCAR conferred drug inducibility to the proximal -2145 bp of the CYP2C9 promoter
      in luciferase assays. Further examination of a -2925-bp promoter construct
      revealed that hCAR cotransfection increased activity 20-fold. Gel shift assays
      confirmed the presence of a distal PB-responsive enhancer module-like enhancer
      module, CAR-responsive enhancer (CAR-RE), between -2900 and -2841 bp consisting
      of two DR-5 nuclear receptor binding motifs capable of binding hCAR, mCAR, and,
      to a lesser extent, human PXR. The majority of binding and hCAR activation is
      derived from the NR1 portion of the CAR-RE. PB treatment did not further increase
      the hCAR activation in any of the constructs. In summary, a new CAR/PXR binding
      site was identified in the CYP2C9 promoter, and this site seems to constitutively
      regulate transcription via a CAR-dependent mechanism; however, it could not be
      shown to account for PB inducibility of the gene.

PMID- 12181451
TI  - Identification of the extracellular loop 2 as the point of interaction between
      the N terminus of the chemokine MIP-1alpha and its CCR1 receptor.
AB  - Macrophage inflammatory peptide-1alpha (MIP-1alpha)/CC-chemokine receptor ligand
      3 is an 8-kDa peptide that induces chemotaxis of various lymphocytes to sites of
      inflammation through interaction with the G protein-coupled chemokine receptors
      CCR1 and CCR5. We recently described the preparation of a photoactivatable
      derivative of MIP-1alpha labeled with a benzophenone group at the extreme N
      terminal end, which is a determinant for the agonist character of chemokines.
      Benzophenone-MIP-1alpha is a full agonist that specifically and covalently labels
      CCR1 and CCR5 receptors upon irradiation. In the present study, we use enzymatic
      and chemical cleavage methods on wild-type and mutated CCR1 receptors to show
      that the N terminus of the chemokine MIP-1alpha interacts in a specific manner
      with the second extracellular loop of the CCR1 receptor, within a segment
      comprising amino acids 178 to 194. This is the first report on the direct
      identification of a contact point between the N terminus of a chemokine and its
      membrane-bound receptor. The work shows that the part of chemokines that is
      endowed with agonist properties interacts with extracellular parts of the
      receptor rather than the transmembrane core of the protein.

PMID- 12181453
TI  - Generation and analysis of constitutively active and physically destabilized
      mutants of the human beta(1)-adrenoceptor.
AB  - Constitutive activity of wild-type and mutant forms of human beta(1)- and beta(2)
      adrenoceptors was measured by guanosine 5'-O-(3-[(35)S]thio)triphosphate
      ([(35)S]GTPgammaS) binding assays using fusion proteins between these receptors
      and G(s)alpha. Constitutive activity of the beta(1)-adrenoceptor is enhanced by
      mutation of Leu(322). The ability of ligands to suppress receptor instability and
      produce up-regulation is often associated with constitutively active mutants.
      Leu(322)Lysbeta(1)-adrenoceptor, but not wild type, was up-regulated by exposure
      to the beta(1)-adrenoceptor selective blocker betaxolol. More extensive sequence
      alterations of the beta(1)-adrenoceptor were generated to mimic the initially
      described constitutively active mutant (CAM) of the beta(2)-adrenoceptor that is
      up-regulated strongly by betaxolol. Substitution of amino acids 316 to 324 of the
      beta(1)-adrenoceptor with the equivalent alpha(1b)-adrenoceptor sequence did not
      result in up-regulation by betaxolol. However, these forms of both beta(1)- and
      beta(2)-adrenoceptors displayed substantial and equivalent constitutive activity.
      The addition of the Leu(322)Lys mutation into the alpha(1b)-adrenoceptor
      substituted beta(1)-adrenoceptor to produce the CAMKbeta(1)-adrenoceptor allowed
      substantially greater levels of up-regulation by betaxolol without enhancement of
      constitutive [(35)S]GTPgammaS binding. Arg(156)Alabeta(1)-adrenoceptor was up
      regulated strongly by betaxolol but displayed lower constitutive activity than
      did other mutants. Binding of [(35)S]GTPgammaS binding to all the fusion proteins
      was increased substantially by isoprenaline. Despite the ability of betaxolol to
      cause up-regulation of many mutants, only for the CAMbeta(2)-adrenoceptor
      G(s)alpha and CAMKbeta(1)-adrenoceptor-G(s)alpha fusion proteins was the basal
      binding of [(35)S]GTPgammaS decreased by betaxolol. Clear resolution between
      receptor constitutive activity and ligand suppression of receptor instability can
      be obtained for mutant beta-adrenoceptors, and potential inverse agonists do not
      function equally at phenotypically apparently equivalent CAM receptors.

PMID- 12181454
TI  - Effects of phosphoinositide 3-kinase on the endothelin-1-induced activation of
      voltage-independent Ca(2+) channels and mitogenesis in Chinese hamster ovary
      cells stably expressing endothelin(a) receptor.
AB  - We recently demonstrated that endothelin-1 (ET-1) activates two types of Ca(2+)
      permeable nonselective cation channel (designated NSCC-1 and NSCC-2) and a store
      operated Ca(2+) channel (SOCC) in Chinese hamster ovary cells expressing
      endothelin(A) receptor (CHO-ET(A)R). In addition, these channels can be
      discriminated using Ca(2+) channel blockers (R,S)-(3,4-dihydro-6,7-dimethoxy
      isochinolin-1-yl)-2-phenyl-N,N-di[2-(2,3,4-trimethoxyphenyl)ethyl]acetamid
      mesylate (LOE 908) and 1-(beta-[3-(4-methoxyphenyl)propoxy]-4-methoxyphenethyl)
      1H-imidazole (SK&F 96365). LOE 908 is a blocker of NSCC-1 and NSCC-2, whereas
      SK&F 96365 is a blocker of SOCC and NSCC-2. In this study, we investigated the
      effects of phosphoinositide 3-kinase (PI3K) on the ET-1-induced activation of
      these channels and mitogenesis in CHO-ET(A)R using wortmannin and 2-(4
      morpholinyl)-8-phenyl-4H-1-benzopyran-4-one (LY 294002), inhibitors of
      phosphoinositide 3-kinase (PI3K). ET-1-induced Ca(2+) influx was partially
      inhibited in CHO-ET(A)R pretreated with wortmannin or LY 294002. In contrast,
      addition of wortmannin or LY 294002 after stimulation with ET-1 did not suppress
      Ca(2+) influx. The Ca(2+) channels activated by ET-1 in wortmannin or LY 294002
      treated CHO-ET(A)R were sensitive to LOE 908 and resistant to SK&F 96365.
      Wortmannin also partially inhibited ET-1-induced mitogenesis. LOE 908, but not
      SK&F 96365, abolished the wortmannin-resistant part of mitogenesis. The IC(50)
      values (~30 nM) of wortmannin for the ET-1-induced Ca(2+) influx and mitogenesis
      were similar to those for the ET-1-induced PI3K activation. In conclusion, NSCC-2
      and SOCC are stimulated by ET-1 via PI3K-dependent cascade, whereas NSCC-1 is
      stimulated via PI3K-independent cascade. Moreover, PI3K seems to be required for
      the activation of the Ca(2+) entry, but not for its maintenance. In addition,
      PI3K is involved in the ET-1-induced mitogenesis that depends on the
      extracellular Ca(2+) influx through SOCC and NSCC-2.

PMID- 12181456
TI  - Design, measurement, and analytical considerations for testing hypotheses
      relative to condom effectiveness against non-viral STIs.

PMID- 12181457
TI  - Chlamydia trachomatis diagnostics.
AB  - Nucleic acid amplification (NAA) assays for the diagnosis of Chlamydia
      trachomatis infections started to appear in the peer reviewed literature about 12
      years ago and during that period we have seen an incredible effort put into the
      development and evaluation of commercially developed NAA kits to diagnose and
      treat infections.

PMID- 12181460
TI  - Assisting medical students to conduct empathic conversations with patients from a
      sexual medicine clinic.
AB  - OBJECTIVE: To describe an exercise, the structure and content of which assists
      medical students to conduct potentially embarrassing conversations concerning
      sexual health which require expression of empathy, to integrate previous
      learning, to identify their further learning needs, and to develop and test
      strategies to meet these needs. METHOD: Students' role play, sequentially,
      speakers (patients) and listeners (clinical students) in a "carousel," in which
      all students are engaged at all times in a sequence of pairings which change at
      rapid intervals. Half way through the exercise, students reflect on the
      experience, identify difficulties and successes, and develop and share strategies
      for experimental use in the second half of the exercise. RESULTS: Qualitative
      comments from the written student evaluations are reported. CONCLUSIONS: The
      exercise provides a formative student centred approach to the integration and
      further development of previously learnt knowledge and skills of value for
      promoting sexual health education. It is useful for educators interested in
      promoting more open and informed learning about sexual health.

PMID- 12181459
TI  - HIV testing and high risk sexual behaviour among London's migrant African
      communities: a participatory research study.
AB  - OBJECTIVES: To describe the demographic and behavioural factors associated with
      HIV testing among migrant Africans in London. METHODS: A cross sectional survey
      of migrants from five sub-Saharan African communities (Congo, Kenya, Uganda,
      Zambia, Zimbabwe) resident in London was carried out. The study formed part of a
      larger community based participatory research initiative with migrant African
      communities in London-the MAYISHA project. Trained, ethnically matched
      interviewers recruited study participants in a variety of community venues. A
      brief self completion questionnaire collected data on demographic
      characteristics, utilisation of sexual health services, HIV testing history,
      sexual behaviour, and attitudes. RESULTS: Valid questionnaires were obtained from
      748 participants (396 men and 352 women), median ages 31 and 27 years,
      respectively. Median length of UK residence was 6 years. 34% of men and 30% of
      women reported ever having had an HIV test. HIV testing was significantly
      associated with age and previous STI diagnosis among women; and additionally,
      nationality, education, employment, and self perceived risk of acquiring HIV
      among men. After controlling for significant demographic variables, previous
      diagnosis of an STI (adjusted odds ratio and 95% confidence interval for men:
      2.96, 1.63 to 5.38, and women 2.03, 1.06 to 3.88) and perceived risk of acquiring
      HIV for men (adjusted OR 2.28, 95%CI 1.34 to 3.90) remained independently
      associated. CONCLUSION: Among these high HIV prevalence migrant communities,
      these data suggest that HIV testing remains largely associated with an
      individual's STI history or self perceived risk. This strategy may be
      inappropriate given the potential for onward and vertical transmission. Antenatal
      HIV testing combined with proactive targeted HIV testing promotion should be
      prioritised.

PMID- 12181458
TI  - Sexually acquired hepatitis.
AB  - OBJECTIVES: To assess current knowledge of sexually transmitted viral hepatitis
      in relation to epidemiology, clinical presentation, management, and diagnosis
      with particular reference to resource-poor settings. METHOD: A search of
      published literature identified through Medline from 1966 to October 2001, the
      Cochrane Library, and reference lists taken from each article obtained. Textword
      and MeSH searches for hepatitis A, B, C, D, E, G, delta, GB virus, GBV-C, and TT
      virus were linked to searches under the textword terms sex$, prevent$, and MeSH
      subheadings, microbiology, complications, drug therapy, therapy, diagnosis,
      epidemiology, transmission, and prevention and control. CONCLUSIONS: In
      heterosexual relationships, hepatitis B is readily transmitted sexually and
      hepatitis C and D less so, with no evidence for sexual transmission of hepatitis
      A. Hepatitis types A-D are all transmissible sexually in male homosexual
      relationships under certain conditions. In resource-poor countries sexual
      transmission is generally only a significant route of transmission for hepatitis
      B.

PMID- 12181461
TI  - HIV infection among people of foreign origin voluntarily tested in Spain. A
      comparison with national subjects.
AB  - OBJECTIVES: To describe exposure categories and HIV prevalence among subjects
      voluntarily tested in Spain by country of origin. METHODS: HIV prevalence and
      exposure categories were compared between national and non-Spanish subjects
      voluntarily tested in 18 sexually transmitted disease/HIV testing clinics from 16
      Spanish cities in 2000. RESULTS: Of 8861 testers, 2810 (31.7%) came from foreign
      countries; 73.1% from Latin America, 9.1% from western Europe, 6.2% from
      central/eastern Europe, 4.4% from northern Africa, and 4.2% from sub-Sahara
      Africa. Among women from Latin America, 78% were sex workers compared to 5.5%
      Spanish women. HIV infection was diagnosed in 170 persons, 34.7% from foreign
      countries. HIV prevalence for Spanish subjects (23% for men and 1.0% for women)
      was significantly different from men and women from Latin America (11.3% and 0.3%
      respectively), Sub-Saharan Africa (9.1% and 7.5% respectively), and women from
      the north of Africa (11.8%). Compared with Spaniards, analyses of persons of the
      same exposure category showed higher HIV prevalence in men who had sex with men
      from Latin America (odds ratio: 4.1; 95% CI: 2.4-6.9), heterosexual men from sub
      Sahara Africa (OR: 19.3; 95% CI: 6.4-58.0), and Latin America (OR: 9.4; 95% CI:
      3.4-25.9), heterosexual women from sub-Sahara Africa (OR: 16.9; 95% CI: 3.5-82.4)
      and from northern Africa (OR: 15.3; 95% CI: 3.2-73.2). CONCLUSIONS: An important
      proportion of HIV testers from these clinics came from foreign countries and some
      groups showed a high prevalence of HIV infection. Specific prevention and testing
      programmes adapted to the needs of migrants in Spain should be developed.

PMID- 12181462
TI  - Factors influencing HIV progression in a seroconverter cohort in Madrid from 1985
      to 1999.
AB  - OBJECTIVE: To study HIV progression from seroconversion over a 15 year period and
      measure the population effectiveness of highly active antiretroviral therapy
      (HAART). METHODS: A cohort study of people with well documented dates of
      seroconversion. Cumulative risk of AIDS and death were calculated by extended
      Kaplan-Meier allowing for late entry. Cox proportional hazards models were used
      to study variables associated with HIV progression. To assess the impact of
      HAART, calendar time was divided in three periods; before 1992, 1992-6, and 1997
      9. RESULTS: From January 1985 to May 2000, 226 seroconverters were identified.
      The median seroconversion interval was 11 months, median seroconversion date was
      March 1993. 202 (89%) were men, 76% of whom were homo/bisexual. A 66% reduction
      in progression to AIDS was observed in 1997-9 compared to 1992-96 (HR 0.34 95%
      CI: 0.16 to 0.70). People with primary education appeared to have faster
      progression to AIDS compared to those with university studies (HR 2.69 95%CI:
      1.17 to 6.16). An 82% reduction in mortality from HIV seroconversion was observed
      in 1997-9 (HR 0.18 95% CI: 0.05 to 0.68) compared to 1992-6. Progression to death
      for people with primary education was twice as fast as for those with university
      education (p 0.0007). People without confirmation of an HIV negative test had
      faster progression (HR 4.47 95% CI: 1.18 to 16.92). CONCLUSIONS: The reduction in
      progression to AIDS and death from seroconversion from 1992-6 to 1997-9 in Madrid
      is likely to be attributable to HAART. HIV progression was faster in subjects
      with primary education; better educational level may be associated with better
      adherence to medication.

PMID- 12181463
TI  - Community effects on the risk of HIV infection in rural Tanzania.
AB  - OBJECTIVES: To investigate the effect of community characteristics on HIV
      prevalence and incidence. METHODS: Data from an open cohort study with
      demographic surveillance, epidemiological surveys, and qualitative research were
      used to examine the association between individual and community risk factors
      with HIV prevalence in 1994-5 and incidence between 1994-5 and 1996-7 among men
      (n=2271) and women (n=2752) living in a rural area in northwest Tanzania. Using
      subvillages as the unit of analysis, community factors investigated were level of
      social and economic activity, ratio of bar workers per male population aged 18
      59, level of community mobility, and distance to the nearest town. Logistic and
      Cox regression models were estimated to assess community effects, controlling for
      multiple individual factors. RESULTS: All four community factors had strong
      effects on HIV transmission. Men who lived in subvillages with the highest level
      of social and economic activity had an odds of being HIV positive that was about
      five times higher (OR=4.71, 95% CI=2.89 to 6.71) than those in places with low
      levels of activity; women in these subvillages had an odds that was twice as high
      (OR=1.92, 95% CI=1.27 to 2.92). After controlling for community effects, the
      effects of some individual factors on the risk of HIV-education, male
      circumcision, type of work, and number of household assets-changed notably. The
      association between HIV incidence and community factors was in the expected
      direction, but did not reach statistical significance (RR=2.07, p=0.10).
      CONCLUSIONS: Results suggest that community characteristics play an important
      part in the spread of HIV in rural Tanzania. Community effects need both to be
      considered in individual risk factor analyses and be given more attention in
      intervention programmes.

PMID- 12181465
TI  - Part time female sex workers in a suburban community in Kenya: a vulnerable
      hidden population.
AB  - BACKGROUND: In sub-Saharan Africa, female sex workers (FSWs) are a vulnerable
      high risk group for the acquisition and transmission of sexually transmitted
      infections (STI) and HIV. OBJECTIVES: To study parameters of sexual behaviour and
      knowledge of STI and HIV, to describe health seeking behaviour related to STI,
      and to measure the prevalence of gonorrhoea, chlamydia, syphilis, and HIV-1, to
      provide baseline data for targeted STI and HIV prevention interventions. METHODS:
      In a cross sectional survey with snowballing recruitment, between February and
      March 2000, 503 self identified FSWs in a suburb in Mombasa, Kenya, were
      interviewed with a structured questionnaire and screened for gonorrhoea,
      chlamydia, syphilis, and HIV-1. RESULTS: The mean number of sexual partners in
      the previous week was 2.8 (SD 1.6). The mean number of non-regular clients and
      regular clients in the previous week was 1.5 (1.0) and 1.0 (0.9) respectively.
      The median weekly income from sex work was $US15. A total of 337 (67%) women had
      an alternative income in the informal sector. 146 (29%) and 145 (45%) never used
      a condom with a client and non-paying partner respectively. The prevalence of
      gonorrhoea, chlamydia, and syphilis was 1.8%, 4.2%, and 2.0% respectively. The
      overall HIV-1 seroprevalence was 30.6%. CONCLUSIONS: There is a large need for
      intensive STI and HIV prevention interventions in part time FSW.

PMID- 12181464
TI  - 15 Month follow up of African children following vaginal cleansing with
      benzalkonium chloride of their HIV infected mothers during late pregnancy and
      delivery.
AB  - OBJECTIVES: To study mother to child HIV-1 transmission (MTCT) and infant
      mortality following benzalkonium chloride (BC) disinfection. METHODS: A
      randomised, double blind phase II placebo controlled trial. Women testing
      positive for HIV-1 infection in prenatal care units in Abidjan, Cote d'Ivoire,
      and Bobo-Dioulasso, Burkina Faso, from November 1996 to April 1997 were eligible,
      with their informed consent. Women self administered daily a vaginal suppository
      of 1% BC (53) or matched placebo (54) from 36 weeks of pregnancy, plus a single
      dose during labour. The neonate was bathed with 1% BC solution or placebo within
      30 minutes after birth. MTCT rate was assessed based on repeated polymerase chain
      reaction (PCR) and serology results. For the present analysis, children were
      followed up to 15 months. RESULTS: A total of 107 women were enrolled. Of 103
      eligible liveborn children, 23 were HIV infected, 75 uninfected, and five of
      indeterminate status. MTCT transmission rate was 24.2% overall (95% confidence
      interval (CI): 14.3% to 30.4%). On an intent to treat basis, the transmission
      rate did not differ between the two groups (23.5%, CI 13.8 to 38.5, in the BC
      group and 24.8%, CI 15.0 to 39.6, in the placebo group at 15 months). Similarly,
      there was no difference in mortality at 15 months (22.9%, CI 13.7 to 36.9, in the
      BC group and 16.5%, CI 9.0 to 29.4, in the placebo group). CONCLUSION: This
      analysis failed to suggest any benefit of BC disinfection on mother to child HIV
      transmission or perinatal and infant mortality.

PMID- 12181466
TI  - Coexistence of urethritis with genital ulcer disease in South Africa: influence
      on provision of syndromic management.
AB  - OBJECTIVE: To assess whether syndromic management of genital ulcer disease was
      sound, if based on the premise that men with genital ulcers rarely have a
      concomitant urethral infection. METHODS: Specimens were taken in 1998 from 186
      mine workers in Carletonville, South Africa, who were seen consecutively with
      genital ulcers. The specimens comprised a swab from the ulcer, a urethral swab
      for a Gram stained smear, and 10-15 ml of a first catch urine sample. The latter
      was tested by ligase chain reaction assays for Neisseria gonorrhoeae and
      Chlamydia trachomatis specific DNA sequences and by a polymerase chain reaction
      (PCR) assay for Mycoplasma genitalium. Ulcer inducing micro-organisms were
      detected either by a multiplex PCR assay, or in the case of lymphogranuloma
      venereum (LGV) serologically, and human immunodeficiency virus (HIV) infection
      was detected by an enzyme linked immunosorbent assay (ELISA) test. RESULTS: Most
      (54%) of the ulcers were chancroidal, 18% were herpetic (HSV type 2), 6.5%
      primary syphilitic, and 3.2% due to LGV. More than one micro-organism was
      detected in 9.1% of the ulcers and less than 10% were undiagnosed. Microscopic
      examination of the urethral smears showed that 99 (53%) of the men had
      urethritis, of whom 45 (45%) were infected with N gonorrhoeae. Of the 54 men
      (55%) who had non-gonococcal urethritis (NGU), 11 (19.6%) harboured C trachomatis
      or M genitalium. Almost two thirds (64.5%) of the men had HIV infection, but this
      did not seem to have influenced the aetiology of the ulcers. Nor was a particular
      ulcer associated with one type of urethritis more than the other. Neither C
      trachomatis nor M genitalium was associated significantly with non-gonococcal
      urethritis (NGU) in either HIV positive or HIV negative men. CONCLUSION: The
      combination of antibiotics used for the management of genital ulcer disease in
      men in this South African mining population needs to be widened to encompass
      frequently occurring concomitant gonococcal urethritis and NGU infections. This
      means treatment with long acting penicillin, combined with ciprofloxacin and
      azithromycin or erythromycin. A similar situation may exist in other geographical
      locations with a need to provide appropriate antimicrobial combinations depending
      on the patterns of infection detected.

PMID- 12181467
TI  - The diagnosis of chlamydia, gonorrhoea, and trichomonas infections by self
      obtained low vaginal swabs, in remote northern Australian clinical practice.
AB  - OBJECTIVE: To examine the diagnostic performance of self obtained low vaginal
      swabs (SOLVS) and polymerase chain reaction (PCR) techniques in the diagnosis of
      Chlamydia trachomatis (CT), Neisseria gonorrhoeae (NG), and Trichomonas vaginalis
      (TV) infection in a variety of clinical practice settings in remote north western
      Australia. DESIGN: A cross sectional field study of microbiological collection
      techniques in women undergoing gynaecological investigation in remote settings
      performed by a variety of practitioner types over 10 months. PARTICIPANTS AND
      SETTING: 349 women from remote towns and communities in the Kimberley region of
      north west Western Australia having gynaecological examinations for clinical
      reasons, well women screening, antenatal screening, and sexual health
      examinations. RESULTS: The overall prevalence of infection in the study
      population based on any positive conventional sample was 9.2%, 7.6%, and 16.1%
      for CT, NG, and TV respectively. The detection rates for CT and NG by SOLVS were
      89% and 96% respectively, compared with 79% and 91% for endocervical swabs and
      79% and 83% for first void urine. SOLVS had a sensitivity of 93% for TV
      detection, equal to that of clinician obtained low vaginal swabs. None of these
      differences reached statistical significance. A combination of SOLVS and first
      void urine detected 96% of the CT cases, 100% of the NG cases, and 96% of TV
      cases. CONCLUSIONS: Self obtained low vaginal swabs are an acceptable, simple and
      sensitive diagnostic sample for the detection of CT, NG, and TV, and have
      particular applications in remote clinical practice and as a screening technique.

PMID- 12181468
TI  - Performance of the rapid plasma reagin and the rapid syphilis screening tests in
      the diagnosis of syphilis in field conditions in rural Africa.
AB  - OBJECTIVES: To assess the rapid plasma reagin (RPR) test performance in the field
      and to evaluate a new rapid syphilis test (RST) as a primary screen for syphilis.
      METHODS: 1325 women of reproductive age from rural communities in the Gambia were
      tested for syphilis seropositivity using a RPR 18 mm circle card and a RST strip.
      Within 1 week a repeat RPR and a TPHA test were carried out using standard
      techniques in the laboratory. RESULTS: Comparing field tests to a diagnosis of
      "active" syphilis defined as laboratory RPR and TPHA positive, the RPR test was
      77.5% sensitive and 94.1% specific; the RST was 75.0% sensitive and 95.2%
      specific. The RST was easier to use and interpret than the RPR test especially
      where field conditions were difficult. In this setting with a low prevalence of
      syphilis in the community (3%), the chance of someone with a positive test being
      confirmed as having serologically active syphilis was less than 50% for both
      tests. CONCLUSIONS: The appropriateness of syphilis screening using RPR testing
      in antenatal clinics and health centres should be questioned if there is a low
      prevalence in the population, conditions for testing are poor, and resources
      limited. There is still an urgent need for an appropriate rapid syphilis test for
      field use.

PMID- 12181469
TI  - Chlamydia trachomatis in non-gonococcal urethritis patients and their
      heterosexual partners: routine testing by polymerase chain reaction.
AB  - OBJECTIVES: To identify the proportion of cases of non-gonococcal urethritis
      (NGU) in which Chlamydia trachomatis was detected in patients and their partners,
      using DNA amplification testing; and to relate the importance of age and symptoms
      to the presence of chlamydial infection and so clarify the aetiology and
      epidemiology of NGU, with a view to reducing the prevalence of chlamydial
      infection in general. METHODS: A 6 month cohort of all newly registered
      heterosexual men diagnosed with NGU, shortly after the introduction of polymerase
      chain reaction (PCR) chlamydial testing in 1997, was reviewed, with particular
      reference to their age and presence of symptoms; where possible, their women
      partners' data were traced. RESULTS: Of 283 NGU patients, 35% were chlamydia
      positive and significantly younger than the chlamydia negative cases (mean ages
      25 and 29 years respectively). 51% NGU patients were symptomatic, of whom 40%
      were chlamydia positive. 43% of all chlamydia positive NGU patients were
      asymptomatic. 36 men had had chlamydia positive index partners. 26% of the 97
      secondary female contacts were chlamydia positive; three had had a negative male
      partner. From 155 men (28% chlamydia positive) no contacts were traceable.
      CONCLUSIONS: In comparison with a previous similar study in 1987-90, using less
      sensitive diagnostic methods, a higher rate of chlamydial infection in NGU was
      detected. Young age and the presence of symptoms were confirmed as important
      factors for chlamydial positivity.

PMID- 12181470
TI  - Mycoplasma genitalium is not associated with adverse outcomes of pregnancy in
      Guinea-Bissau.
AB  - OBJECTIVE: To evaluate the impact of Mycoplasma genitalium on the outcome of
      pregnancy. METHODS: Cervical samples from women who had previously participated
      in a case-control study (designed to assess the impact of syphilis and HIV-2 on
      the outcome of pregnancy in Guinea-Bissau) were processed using a PCR assay to
      detect the presence of M genitalium. Controls were women who had delivered a term
      neonate with a birth weight over 2500 g. Cases were classified into four groups
      of mothers according to the outcome of pregnancy: stillbirths, spontaneous
      abortions, premature deliveries, and small for gestational age (SGA) babies.
      RESULTS: Among the 1014 women included in this study, 6.2% were infected with M
      genitalium. M genitalium infection was not significantly associated with any of
      the adverse outcomes of pregnancy studied. Odds ratios (OR) for premature or SGA
      delivery in the presence of M genitalium infection were 1.37 (95% CI 0.69 to
      2.60) and 0.44 (95% CI 0.01 to 2.75), respectively. For abortions and
      stillbirths, OR were respectively 0.61 (95% CI 0.07 to 2.51) and 1.07 (95% CI
      0.42 to 2.42). CONCLUSION: M genitalium appears not to have a deleterious impact
      on the outcome of pregnancy.

PMID- 12181471
TI  - The historical role and education of nurses for the care and management of
      sexually transmitted infections in the United Kingdom: 1 role.
AB  - Nurses have been involved in the management of sexually transmitted infections
      (STIs) well before the era of Florence Nightingale. Their role has varied from
      that of the technician, almoner, counsellor, and doctor's assistant, to one in
      which they are able to provide first line management of STIs in nurse led
      clinics. However, changes to the role of the nurse have not been entirely through
      choice. It appears that nurses have often been called upon in times of crisis and
      need-their role often evolving only through demand for services and personnel.
      Barriers to developing the role of the nurse continue to exist as we move into
      the 21st century. From Lock hospitals to specialised genitourinary medicine
      clinics, this historical review looks at how the role of the nurse has evolved
      over the past 150 years and suggests how past lessons can help enhance the
      contribution nurses will make to the future of STI management and control.

PMID- 12181472
TI  - The historical role and education of nurses for the care and management of
      sexually transmitted infections in the United Kingdom: 2 education and training.
AB  - The beginning of the 20th century saw the first attempts to educate nurses about
      sexually transmitted infections (STIs) in the United Kingdom. Throughout the
      century, numerous individuals and organisations campaigned for improved STI
      awareness education for nurses. Education initiatives gradually moved from the
      more generic nurse training programmes to the specialist courses for
      genitourinary medicine (GUM) nurses. Even so, it wasn't until the 1970s that
      these specialist courses were successfully implemented and sustained. Following a
      detailed review of nursing education and STIs over the past century, this paper
      speculates why programmes of STI education have never been sustained for the
      general nursing workforce. It then considers possible developments for future
      education agendas that will ultimately enable nurses to contribute more readily
      to the challenges that national sexual health and nursing strategies currently
      propose.

PMID- 12181473
TI  - Perianal Crohn's disease masquerading as perianal warts.

PMID- 12181475
TI  - Multicentric plasma cell variant Castleman's disease mimicking intrapulmonary
      malignancy.

PMID- 12181480
TI  - Vulvovaginitis due to fluconazole resistant Candida albicans following self
      treatment with non-prescribed triazoles.

PMID- 12181481
TI  - Resurgence of syphilis in England.

PMID- 12181482
TI  - Adult and paediatric contact immunotherapy with squaric acid dibutylester (SADBE)
      for recurrent, multiple, resistant, mucocutaneous anogenital warts.

PMID- 12181483
TI  - Will the legalisation of street sex work improve health?

PMID- 12181484
TI  - Recreational drug use by GUM clinic attendees.

PMID- 12181485
TI  - HIV negative certification and sexual health issues facing performers in the
      adult entertainment industry in the UK.

PMID- 12181488
TI  - Identification of the binding sites of regulatory proteins in bacterial genomes.
AB  - We present an algorithm that extracts the binding sites (represented by position
      specific weight matrices) for many different transcription factors from the
      regulatory regions of a genome, without the need for delineating groups of
      coregulated genes. The algorithm uses the fact that many DNA-binding proteins in
      bacteria bind to a bipartite motif with two short segments more conserved than
      the intervening region. It identifies all statistically significant patterns of
      the form W(1)N(x)W(2), where W(1) and W(2) are two short oligonucleotides
      separated by x arbitrary bases, and groups them into clusters of similar
      patterns. These clusters are then used to derive quantitative recognition
      profiles of putative regulatory proteins. For a given cluster, the algorithm
      finds the matching sequences plus the flanking regions in the genome and performs
      a multiple sequence alignment to derive position-specific weight matrices. We
      have analyzed the Escherichia coli genome with this algorithm and found
      approximately 1,500 significant patterns, which give rise to approximately 160
      distinct position-specific weight matrices. A fraction of these matrices match
      the binding sites of one-third of the approximately 60 characterized
      transcription factors with high statistical significance. Many of the remaining
      matrices are likely to describe binding sites and regulons of uncharacterized
      transcription factors. The significance of these matrices was evaluated by their
      specificity, the location of the predicted sites, and the biological functions of
      the corresponding regulons, allowing us to suggest putative regulatory functions.
      The algorithm is efficient for analyzing newly sequenced bacterial genomes for
      which little is known about transcriptional regulation.

PMID- 12181489
TI  - Mutations and common polymorphisms in ADAMTS13 gene responsible for von
      Willebrand factor-cleaving protease activity.
AB  - von Willebrand factor (VWF) is synthesized primarily in vascular endothelial
      cells and secreted into the plasma as unusually large VWF multimers. Normally,
      these multimers are quickly degraded into smaller forms by a plasma
      metalloproteinase, VWF-cleaving protease (VWF-CP). Decreases in the activity of
      this enzyme result in congenital and acquired thrombotic thrombocytopenic purpura
      (TTP). The human VWF-CP has recently been purified. Cloning of the corresponding
      cDNA revealed that the 1,427-aa polypeptide is a member of the ADAMTS gene
      family, termed ADAMTS13. Twelve rare mutations in this gene have been identified
      in patients with congenital TTP. Here, we report missense and nonsense mutations
      in two Japanese families with Upshaw-Schulman syndrome, congenital TTP with
      neonatal onset and frequent relapses. The comparison of individual ADAMTS13
      genotypes and plasma VWF-CP activities indicated that the R268P, Q449stop, and
      C508Y mutations abrogated activity of the enzyme, whereas the P475S mutant
      retained low but significant activity. The effects of these mutations were
      further confirmed by expression analysis in HeLa cells. Recombinant VWF-CP
      containing either the R268P or C508Y mutations was not secreted from cells. In
      contrast, Q449stop and P475S mutants were normally secreted but demonstrated
      minimal activity. Genotype analysis of 364 Japanese subjects revealed that P475S
      is heterozygous in 9.6% of individuals, suggesting that approximately 10% of the
      Japanese population possesses reduced VWF-CP activity. We report on a single
      nucleotide polymorphism associated with alterations in VWF-CP activity; it will
      be important to assess this single-nucleotide polymorphism as a risk factor for
      thrombotic disorders.

PMID- 12181490
TI  - Transmission of prions.
AB  - The "protein only" hypothesis states that the infectious agent causing
      transmissible spongiform encephalopathies is a conformational isomer of PrP, a
      host protein predominantly expressed in brain, and is strongly supported by many
      lines of evidence. Prion diseases are so far unique among conformational diseases
      in that they are transmissible, not only experimentally but also by natural
      routes, mainly by ingestion. A striking feature of prions is their extraordinary
      resistance to conventional sterilization procedures, and their capacity to bind
      to surfaces of metal and plastic without losing infectivity. This property, first
      observed in a clinical setting, is now being investigated in experimental
      settings, both in animals and in cell culture.

PMID- 12181491
TI  - High molecular weight RNAs and small interfering RNAs induce systemic
      posttranscriptional gene silencing in plants.
AB  - Posttranscriptional gene silencing (PTGS) in transgenic plants is an epigenetic
      form of RNA degradation related to PTGS and RNA interference (RNAi) in fungi and
      animals. Evidence suggests that transgene loci and RNA viruses can generate
      double-stranded RNAs similar in sequence to the transcribed region of target
      genes, which then undergo endonucleolytic cleavage to generate small interfering
      RNAs (siRNA) that promote degradation of cognate RNAs. The silent state in
      transgenic plants and in Caenorhabditis elegans can spread systemically, implying
      that mobile silencing signals exist. Neither the chemical nature of these signals
      nor their exact source in the PTGS pathway is known. Here, we use a positive
      marker system and real-time monitoring of green fluorescent protein expression to
      show that large sense, antisense, and double-stranded RNAs as well as double
      stranded siRNAs delivered biolistically into plant cells trigger silencing
      capable of spreading locally and systemically. Systemically silenced leaves show
      greatly reduced levels of target RNA and accumulate siRNAs, confirming that RNA
      can induce systemic PTGS. The induced siRNAs represent parts of the target RNA
      that are outside of the region of homology with the triggering siRNA. Our results
      imply that siRNAs themselves or intermediates induced by siRNAs could comprise
      silencing signals and that these signals induce self-amplifying production of
      siRNAs.

PMID- 12181494
TI  - Health beliefs of first-degree relatives of individuals with colorectal cancer
      and participation in health maintenance visits: a population-based survey.
AB  - The occurrence of colorectal cancer (CRC) in two or more close relatives by
      chance is relatively common, and a family history of CRC is recognized as a risk
      factor for CRC. The purpose of this study was to identify variables associated
      with participation of first-degree relatives (FDRs) of individuals diagnosed with
      CRC in health maintenance visits with healthcare providers. Data were collected
      from a survey mailed to patients (n = 1081) diagnosed with CRC under age 60 years
      who were identified by the Pennsylvania Cancer Registry. An enclosure was also
      included in the mailing for their FDRs. Of the 1,081 people contacted, 174
      registry patients and 90 FDRs agreed to participate in this study. A logistic
      regression model was built, and constructs of the Health Belief Model and
      selected sociodemographic variables (age, gender, level of education) were
      entered with participation in health maintenance visits as the dependent
      variable. The analysis revealed 2 Health Belief Model variables (perceived
      barriers and perceived seriousness) and 1 sociodemographic variable (level of
      education) as predictive of an FDR's participation in health maintenance visits.
      The findings from this study suggest that FDRs of individuals with CRC do not
      perceive that they are at risk for CRC, despite their family history. These data
      also provide the foundation for future studies aimed at the development of
      interventions to increase awareness of the importance and benefits of screening
      for relatives of individuals with CRC.

PMID- 12181493
TI  - TCL1 participates in early embryonic development and is overexpressed in human
      seminomas.
AB  - Overexpression of the TCL1 oncogene has been shown to play a causative role in T
      cell leukemias of humans and mice. The characterization of Tcl1-deficient mice in
      these studies indicates an important developmental role for Tcl1 in early
      embryogenesis. In wild-type embryos, Tcl1 is abundant in the first three mitotic
      cycles, during which it shuttles between nuclei and the embryo cortical regions
      in a cell-cycle-dependent fashion. The absence of this protein in early
      embryogenesis results in reduced fertility of female mice. The present studies
      elucidate the mechanism responsible for the reduced female fertility through
      analysis of the oogenesis stages and early embryo development in Tcl1-deficient
      mice. Even though Tcl1(-/-) females display normal oogenesis and rates of oocyte
      maturation/ovulation and fertilization, the lack of maternally derived Tcl1
      impairs the embryo's ability to undergo normal cleavage and develop to the morula
      stage, especially under in vitro culture conditions. Beyond this crisis point,
      differentiative traits of zygotic genome activation and embryo compaction can
      take place normally. In contrast with this unanticipated role in early
      embryogenesis, we observed an overexpression of TCL1 in human seminomas. This
      finding suggests that TCL1 dysregulation could contribute to the development of
      this germinal cell cancer as well as lymphoid malignancies.

PMID- 12181492
TI  - Vascular endothelial growth factor (VEGF) stimulates neurogenesis in vitro and in
      vivo.
AB  - Vascular endothelial growth factor (VEGF) is an angiogenic protein with
      neurotrophic and neuroprotective effects. Because VEGF promotes the proliferation
      of vascular endothelial cells, we examined the possibility that it also
      stimulates the proliferation of neuronal precursors in murine cerebral cortical
      cultures and in adult rat brain in vivo. VEGF (>10 ng/ml) stimulated 5-bromo-2'
      deoxyuridine (BrdUrd) incorporation into cells that expressed immature neuronal
      marker proteins and increased cell number in cultures by 20-30%. Cultured cells
      labeled by BrdUrd expressed VEGFR2/Flk-1, but not VEGFR1/Flt-1 receptors, and the
      effect of VEGF was blocked by the VEGFR2/Flk-1 receptor tyrosine kinase inhibitor
      SU1498. Intracerebroventricular administration of VEGF into rat brain increased
      BrdUrd labeling of cells in the subventricular zone (SVZ) and the subgranular
      zone (SGZ) of the hippocampal dentate gyrus (DG), where VEGFR2/Flk-1 was
      colocalized with the immature neuronal marker, doublecortin (Dcx). The increase
      in BrdUrd labeling after the administration of VEGF was caused by an increase in
      cell proliferation, rather than a decrease in cell death, because VEGF did not
      reduce caspase-3 cleavage in SVZ or SGZ. Cells labeled with BrdUrd after VEGF
      treatment in vivo include immature and mature neurons, astroglia, and endothelial
      cells. These findings implicate the angiogenesis factor VEGF in neurogenesis as
      well.

PMID- 12181495
TI  - Evaluation of an education program for patients with breast cancer receiving
      radiation therapy.
AB  - The acquisition of knowledge is presumed to be part of the coping process for
      women facing increased stress because of a breast cancer diagnosis. The purpose
      of this study was to evaluate the impact of an education program on the perceived
      adequacy of knowledge of patients with breast cancer receiving radiation therapy.
      Second, the intent was to investigate the patients' preferences regarding
      involvement in decision making, amount and type of information wanted, and
      preferred information-seeking activities.A priori quota sampling was planned to
      ensure that at least 20 subjects were recruited to each of 3 age categories,
      assumed to represent premenopausal, perimenopausal, and postmenopausal patients
      with breast cancer receiving radiation therapy. Subjects (N = 79) completed
      questionnaires before and after the evidence-based education program. The
      education consisted of a 20-minute interactive video (first session);
      individualized education, including technical procedures and self-care (second
      session); and a 1-hour class (third session). Individual teaching as required was
      provided afterward during radiation therapy.Significant increases in perceived
      adequacy of knowledge scores indicate that the program was effective, especially
      with information concerning disease and treatment for postmenopausal subjects.
      Subjects' participation in 7 of the information-seeking strategies suggests that
      many had actively sought information before undergoing radiation therapy.
      Preferences for information that may be indicative of individual coping patterns
      were similar for more than half of the subjects. The majority preferred as many
      details as possible, as much information as possible (good and bad), and to
      participate in decision making. However, not all subjects wanted complete
      information, except for the information on all side effects. Findings from this
      study suggest that individual patients' information preferences, priority
      information needs, and preferred information-seeking activities should be
      identified early and incorporated within educational programs to target resources
      and maximize the likelihood that positive patient outcomes will result.

PMID- 12181496
TI  - Breast cancer risk-factor and screening awareness among women nurses and teachers
      in Amman, Jordan.
AB  - Breast cancer awareness studies of women in Jordan do not exist. This study used
      data from 163 nurses and 178 teachers surveyed in Amman to determine 2 dimensions
      of breast cancer awareness: general breast cancer awareness, defined as knowledge
      of risk factors associated with the disease and breast cancer screening
      awareness, defined as knowledge of breast self-examination and mammography. The
      survey instrument was based on 2 previously validated knowledge-based
      questionnaires in the literature (Breast Cancer Knowledge Test and the
      Comprehensive Breast Cancer Questionnaire). Analysis of covariance indicated that
      family history was associated with general breast cancer awareness. Profession,
      age, and family history significantly influenced breast cancer screening
      awareness. The average percentage of correct responses to general breast cancer
      awareness was adjusted for select covariates (adjusted means). The adjusted mean
      general awareness score for nurses was not significantly different from that of
      teachers (P =.8470). Nurses were more aware than teachers of the importance of
      breast cancer screening and its techniques. The adjusted mean screening awareness
      score for nurses was 88.3%, compared with 73.1% for teachers (P <.0001). These
      results provide important information about the level of breast cancer awareness
      among women nurses and teachers in Jordan and may be useful for developing future
      prevention and screening education programs.

PMID- 12181497
TI  - Fatigue in patients with breast cancer receiving adjuvant chemotherapy: a review
      of the literature.
AB  - The aim of this literature review was to evaluate the prevalence and course of
      fatigue in patients with breast cancer undergoing adjuvant chemotherapy and to
      examine factors relating to fatigue. Fatigue is one of the most common side
      effects of chemotherapy. High and fluctuating prevalence rates of fatigue have
      been found not only during but also after adjuvant chemotherapy. The intensity of
      fatigue seems to be stable throughout the treatment cycles, despite the common
      perception that more chemotherapy treatments lead to greater fatigue. The first
      two days after a chemotherapy treatment seem to be the worst period. The
      influence of factors such as pain, impaired quality of sleep, and depression are
      be highly consistent across several studies, although it is often not clear
      whether it is the symptoms that cause the fatigue or vice versa. The outcomes of
      the studies indicate that several symptoms are interrelated in a network of
      symptoms. Factors such as changes in weight, menopausal symptoms, coping, social
      support, and biochemical changes have been mentioned in the literature as
      potentially contributing to fatigue. Results have been conflicting and need
      further study.

PMID- 12181498
TI  - Facilitating patients' coping with fatigue during chemotherapy-pilot outcomes.
AB  - A pilot study was conducted to develop and test a nursing intervention to
      facilitate the management of fatigue in patients receiving chemotherapy. The
      intervention, named the "Beating Fatigue" program, has 4 elements:
      assessment/monitoring, education, coaching in the management of fatigue, and
      provision of emotional support. Beating Fatigue was implemented with and
      evaluated by 8 patients. Overall, patients were very positive about the program
      and perceived the opportunity to talk to someone about fatigue as the most
      beneficial strategy within the program, although individual patients varied in
      which aspect they most preferred. Data from the pilot work supported the view
      that a multifaceted approach to the management of cancer-related fatigue is
      appropriate because it enables an intervention package to be tailored to an
      individual's requirements. The approach appeared both feasible and practical.
      Although numeric data were limited, there was some evidence that the approach had
      the capacity to lessen fatigue and enhance emotional well-being.

PMID- 12181499
TI  - Symptom distresses and coping strategies in patients with non-small cell lung
      cancer.
AB  - The purpose of this study is to understand the correlation of symptom distresses
      and coping strategies of patients with lung cancer. Seventy-three patients with
      non-small cell lung cancer from the cancer center or ward in the two medical
      centers located in northern Taiwan participated. The instruments used in this
      study were the Symptom Distress Scale and Coping Strategies Scale. The results of
      the study showed that the degree of symptom distress during the therapeutic
      period was mild to moderate. When patients were confronted with symptom distress,
      they combined problem- and emotion-focused coping strategies. Participants with
      higher physical symptom distress had higher psychological distress and emotion
      focused coping strategy frequency. It was also found that the distress of tension
      anxiety and age explained 39.4% of variance in physical symptom distresses. The
      physical symptom distresses and the frequency of emotion-focused coping strategy
      frequency explained 48.8% of variance in the psychologic symptom distresses.
      Finally, it is recommend that a support group be established to enable sharing of
      experiences and emotional support among patients.

PMID- 12181502
TI  - Prayer in people with cancer.
AB  - The purpose of this study was to adapt an instrument to assess prayer activities,
      experiences, and attitudes for people with cancer. A cross-sectional
      correlational research design was used to study 32 adults (24 women and 8 men) at
      3 urban oncology and 2 radiation clinics. The prayer scale was adapted for people
      with cancer by the author, reviewed by measurement and content experts, and
      tested by administration to 32 people with a variety of cancers. Expert review
      supported the content validity of the adapted instrument. Instrument subscales
      had acceptable reliability for internal consistency. The 3 prayer scale subscales
      were moderately correlated to perceived relationship with God. Results
      demonstrated that high scores on the frequency of prayer subscale were associated
      with low levels of education and functional status and high presence of
      metastasis at diagnosis. Reports of more prayer activity were related to low
      levels of functional status. Additionally, those reporting low levels of physical
      health status had more prayer experiences. The prayer scale is a sensitive
      instrument for assessing prayer activities, experiences, and attitudes of people
      with cancer. Prayer is a valuable internal resource, which can lessen the effect
      of cancer.

PMID- 12181500
TI  - Being in a lived retreat--embodied meaning of alleviated suffering.
AB  - Meanings of alleviated suffering in persons living with life-threatening cancer
      are explored in this life-world phenomenologic study. In repeated conversations,
      16 patients with cancer who were receiving palliative care shared their embodied
      experiences in personal narratives. When interpreting the narratives, the
      following meanings of experiencing alleviation of suffering were disclosed: an
      endurable body being independent and feeling at home, feelings of connectedness,
      taking a long view of the suffering, being lifted out of the suffering, and an
      inner peace. Movements that were found in alleviation were dampening the
      suffering, arousing a zest for life, and focusing on both the present and the
      patient's dignity. As an interpreted whole, alleviation of suffering was found to
      be an embodied experience of "being in a lived retreat." This is a symbolic place
      owned by the person and is experienced in either the company of others or
      solitude. This lived retreat can provide a feeling of being at home, creating
      peace, rest, confidence, and breathing space in the person's suffering. It means
      coping with the altered lived body and feeling dignified. This is a personal
      experience that is both intersubjectively created and dependent. The importance
      of openness and responsibility in palliative care is emphasized in the findings
      and the notion of control of suffering in palliative care is accordingly
      rejected.

PMID- 12181504
TI  - Recruits from overseas need better assessment and support.

PMID- 12181503
TI  - People who have had strokes are receiving inadequate care.

PMID- 12181505
TI  - Nurse who volunteered to take a group of patients on holiday.

PMID- 12181506
TI  - A survey of nurses' assessment of peripheral intravenous catheters.
AB  - The purpose of this survey was to improve nursing care of patients with
      peripheral intravenous catheters (PVCs), focusing on assessment of the PVC site
      for infection. The survey was conducted in 20 wards by an infection control nurse
      (ICN), recording data on assessment, site infection and removal/resiting of PVCs.
      Nursing staff were interviewed on assessment of the PVC site and nursing
      interventions were recorded. A total of 554 PVCs in 397 patients were surveyed of
      which 28 (5%) had site infection. There was no related bloodstream infection
      (BSI). Overall, PVCs were assessed 450 (81%) times by nurses. Malfunction was
      reported 95 (17%) times, pain 28 (5%) times and pyrexia 10 (2%) times.
      Characteristics that showed significant difference between 28 infected and 526
      non-infected PVCs included when nurses assessed PVCs as infected, and nurses'
      intervention for PVCs inserted for 1-3 days' duration. Other characteristics were
      resiting PVCs when associated with malfunction and also resiting because of pain.
      The involvement of the ICN was likely to have contributed to the low infection
      rate. While not conclusive this survey identified characteristics between
      infected and non-infected PVCs that may have been associated with this low
      infection rate, namely, nurses' overall intervention in PVC care and assessment
      that is focused on identifying infection, and resiting for malfunction and pain.
      These are simple assessment and intervention measures that should not require the
      assignment of a dedicated ICN, but which are within the capabilities of all
      healthcare workers entrusted with PVC care.

PMID- 12181507
TI  - Medical devices regulations and the Medical Devices Agency.
AB  - Pansy suffered from a chronic lung condition that required frequent courses of
      antibiotics. As her veins were poor and cannulation was difficult, a passport was
      inserted into a vein in her arm in which antibiotics and other solutions were
      administered. After three courses of antibiotics over the course of several
      weeks, the nurses had difficulty in administering the medication through the
      passport but finally succeeded. Subsequently, during a routine X-ray of her
      lungs, it was discovered that the tube connected with the reservoir had become
      disconnected and had moved down the vein towards the heart.

PMID- 12181508
TI  - Older people who smoke: why nurses should help them to stop.
AB  - Smoking is the greatest preventable cause of ill health and premature death in
      the UK. Although the prevalence of smoking is lower among adults over 65 years
      than in younger age groups, the actual number of older smokers is increasing
      steadily as the proportion of older adults in the population rises. If nurses are
      to function effectively in their role as health promoters it is important that
      they base their practice on appropriate research-based evidence. In this article
      we discuss the current evidence on the health consequences of smoking in later
      life and the benefits of cessation. We provide information on approaches that
      discuss some of the barriers to behavioural change. Our aim is to provide nurses
      with information that will help them to help older smokers make informed choices.

PMID- 12181510
TI  - What do patients want to happen to their dentures before surgery?
AB  - The removal of dentures before having an anaesthetic can be an undignified and
      distressing event. However, there has been a gradual change in practice and
      dentures are now often left in place during an anaesthetic. This enquiry into
      patients' preferences was carried out to find out what patients would like to
      happen to their dentures, and to see if there were any differences in opinions
      among age groups. A postal questionnaire was sent out to patients who wore
      dentures following discharge after surgery. One hundred replies were analysed.
      There was a spread of opinions across the age groups and by gender. Nurses need
      to allow patients the choice of what to do in relation to their dentures when
      going to theatre, although the anaesthetist must make the final decision of
      whether or not to remove them immediately before the anaesthetic if they feel
      patient safety could be compromised.

PMID- 12181509
TI  - Hearing disability: a source of distress for older people and carers.
AB  - Many older people develop hearing disability: however, only a small proportion
      who would benefit from a hearing aid own one. Communication is a shared
      experience that can be substantially limited by hearing difficulty, so this lack
      of hearing aid provision is likely to affect both individuals and those around
      them. This study, a randomized, controlled trial, was designed to examine the
      influence of hearing aid provision on dependent older people and caring family
      members who lived together within multigeneration households. A total of 63
      intervention families and 70 control group families participated in the trial. We
      found that hearing disability and handicap are related to reduced well-being and
      depression in older people, and in turn these are related to increased levels of
      carer distress. Of the 63 older people in the intervention group fitted with
      hearing aids, all but one was experiencing benefit at 6 months, although no
      changes in depression were detected. Hearing aids significantly reduced the
      carer's perception of related difficulties and was a welcome intervention.

PMID- 12181511
TI  - An introduction to clinical negligence: nurses and the law.
AB  - Clinical negligence is a serious problem in the NHS, with claims and costs rising
      steadily. In order to understand the system fully, reference must be made to the
      increasingly complex and developing NHS quality regulation and management
      structure and the law must be considered in this context. This series of articles
      will look at the concept of clinical negligence and examine some of the legal
      issues that arise.

PMID- 12181512
TI  - Point-of-care testing and recognizing and preventing errors.
AB  - Jenny, the practice nurse of a busy GP surgery, was asked to carry out a
      commercially available test to exclude a diagnosis of infectious mononucleosis.
      The test was negative. The patient was prescribed amoxycillin and later developed
      a severe rash. However, the blood tests from the local pathology laboratory
      showed that the patient did have infectious mononucleosis. The GP discovered from
      colleagues that over the last few weeks other patients as the surgery had been
      recorded as having negative tests but positive laboratory results had later
      followed.

PMID- 12181513
TI  - Modern students suffer from acute reality shock.

PMID- 12181514
TI  - Reality bites on Big Brother.

PMID- 12181515
TI  - The costs of long-term catheterization in the community.
AB  - The prevalence of long-term catheterization in the adult population is of the
      order of 0.03-0.07%, rising to 0.5% in those over 75 years and 2% in those over
      85 years old. Studies have shown that the prevalence of urinary incontinence
      increases with age and is higher in females. Little is known about the costs of
      long-term catheterization, which have consequences for care decisions. A pilot
      study was conducted to test (a) the applicability in the UK of a methodology
      developed in the USA for measuring the cost of long-term catheterization in
      community-based patients, and (b) the feasibility of using it in larger-scale
      community-based studies. The study made use of the method developed in the USA by
      Wagner and Hu (1998) to assess the true costs in the population. Patients were
      selected in order to represent as broad as possible a range of underlying disease
      processes and social circumstances. Eight patients were selected, drawn from 3
      distinct groups of patients. The pilot study demonstrated wide variation in
      direct costs for 7 patients living in the community over a 3-month period,
      ranging from pound 118.80 to pound 2585.26. Since staffing is - for the most part
      - the most significant cost element, this indicates significant variation in
      levels of need. Resources deployed for one nursing procedure clearly impact on
      opportunities to undertake other procedures. An understanding of the costs of any
      procedure is necessary in order to make best use of the limited resources
      available.

PMID- 12181516
TI  - Schizophrenia: management and care in the community.
AB  - The move to community care has resulted in many more individuals with severe
      mental health needs relying on community services. Community facilities did not
      receive the proceeds from hospital closures and this had led to inadequate
      provision and facilities for individuals with severe mental health needs. There
      also appears to have been a lack of effective interventions and skills for
      dealing with this specific client group. The National Framework Strategy
      (Department of Health, 1999) for mental health outlines ways to modernize mental
      health services and aims to ensure that they will be more accessible, more
      effective and coordinated across health and social care. Over the past decade,
      there has been a great deal of research examining the effectiveness of
      psychosocial and family interventions for individuals with psychosis. This
      article discusses how such interventions could address some of the shortcomings
      of community care for the severely mentally ill.

PMID- 12181517
TI  - The child patient and consent to treatment: legal overview.
AB  - The giving of consent by the patient before medical treatment is a central tenet
      of medical law. Although it may be fairly clear when an adult patient has given
      consent, the situation can be less clear, and more complex, when a child patient
      is involved. This article seeks to explore the legal issues and concepts that
      arise when treating a minor, and to show how the courts and legal process may
      become involved.

PMID- 12181518
TI  - Bowlby's attachment theory: implications for health visiting.
AB  - This article reviews the current state of research in attachment theory. It also
      examines the relations between attachment, child care and development, and the
      significance of attachment to adult functioning and well-being. It seems likely
      that humans need close emotional relationships or bonds with others. This need
      applies particularly to infants, who look to parents or other care givers for
      love and security. The best-known psychological explanation of this need is
      attachment theory, which has been influential in increasing our understanding of
      the early mother-infant relationship, and in the formulation of guidelines for
      child care (Melhuish, 1998). Good-quality parental care may be difficult to
      define, and questions remain regarding the nature of child care and the
      consequences that it can have for later development. This article concludes with
      a discussion of the possible implications for health-visitor intervention within
      families, which are intended to improve the quality of the relationship between
      parents or care givers and the infant.

PMID- 12181521
TI  - Putting fever in perspective.

PMID- 12181519
TI  - Faculty practice: a model to bridge the theory-practice divide.
AB  - It has been suggested that as a result of nurse education withdrawing from the
      clinical setting and becoming established in institutions of higher education,
      there has been a separation of theory from practice. Recognition of the theory
      practice gap by clinicians and professional bodies has led to calls for nurse
      educators to retain a clinical focus. Faculty practice is described and
      critically discussed as a model of practice to bridge the theory-practice divide.
      In this article, the author presents the results of a 6-month pilot study to
      implement such a model within a community trust, and suggests that the
      development of such initiatives will foster collaborative working and improve
      nurse education and patient care.

PMID- 12181523
TI  - Cellular pattern formation in the retina: retinal regeneration as a model system.
AB  - Like many structures in the central nervous system, the neural retina is highly
      organized at the cellular level. Examples of this cellular organization include
      the laminar profile of the vertebrate retina, the hexagonal array of ommatidia in
      the retinas of insects, and non-random two-dimensional patterns of specific
      vertebrate retinal neurons. These organized cellular ensembles are taxonomically
      robust, and their importance in visual processing is, although typically not well
      understood, virtually axiomatic. The presence of non-random cellular patterns in
      the retina also begs questions concerning the spatial nature of the patterns, and
      the underlying mechanisms that coordinate their assembly during retinal
      development and growth. What are the spatial characteristics of the non-random
      cellular patterns? What molecular signaling schemes might account for their
      assembly? What are good model systems for investigating these issues? In this
      review we attempt to provide some preliminary answers to these questions. We
      present recent advances in our understanding of cellular patterns in the
      vertebrate retina and the mechanisms that underlie their assembly, the ability of
      adult anamniote retinas to regenerate following injury, and how these seemingly
      disparate topics can be successfully merged into an effort to better understand
      both processes. We combine insights from retinal assembly mechanisms in
      Drosophila with empirical, quantitative, and theoretical investigations in
      vertebrates, to propose an inclusive model for retinal cell patterning.

PMID- 12181522
TI  - Clinical phenotype and linkage analysis of the congenital fibrosis of the
      extraocular muscles in an Indian family.
AB  - PURPOSE: To describe the clinical phenotype and linkage analysis of the
      congenital fibrosis of the extraocular muscles (CFEOM) in an Indian family.
      METHODS: Individuals were examined and their peripheral blood samples were
      withdrawn for genetic analysis. The disorder was tested for linkage to two known
      autosomal dominant CFEOM loci on chromosome 12p11.2-q12 (CFEOM1) and chromosome
      16q24 (CFEOM3) using microsatellite markers. RESULTS: Nine individuals including
      seven affecteds participated in the study. All seven affecteds had a classic form
      of CFEOM which included congenital bilateral ptosis, hypotropia, and chin
      elevation. The disorder segregated as an autosomal dominant trait in this family.
      The maximum simulated lod score in this family was 2.02. Linkage to CFEOM3 was
      excluded (Z<-2.00), whereas analysis of chromosome 12 markers was positive. The
      maximum observed two-point lod score was 1.8 (given the size and structure of the
      family) at theta=0 with marker D12S345. Markers D12S61, D12S1631, D12S87,
      D12S345, D12S59, D12S1048, and D12S1668 cosegregated with the disease locus in
      all affecteds. Haplotype analysis showed that the candidate region spanned the
      centromere. CONCLUSIONS: The present data showed a classic CFEOM phenotype in an
      Indian family. The family's phenotype is consistent with linkage to CFEOM1 locus
      on chromosome 12p11.2-q12.

PMID- 12181524
TI  - A decisive effort?

PMID- 12181526
TI  - Breaking down biological borders.

PMID- 12181525
TI  - Small world, big opportunities.

PMID- 12181527
TI  - Save starry nights.

PMID- 12181528
TI  - Slowdown will undermine reform.

PMID- 12181530
TI  - Senators attack Pentagon over weak state of defence research.

PMID- 12181531
TI  - Scientists seek safety in secrets of the soundbite.

PMID- 12181532
TI  - French minister plans shake-up for research.

PMID- 12181533
TI  - Climate model under fire as rains fail India.

PMID- 12181535
TI  - Top projects suffer as medical funding falters.

PMID- 12181537
TI  - Troubled waters.

PMID- 12181538
TI  - Caught on camera.

PMID- 12181539
TI  - Plant mathematics and Fibonacci's flowers.

PMID- 12181540
TI  - Macroecology is distinct from biogeography.

PMID- 12181541
TI  - The search for general principles in ecology.

PMID- 12181546
TI  - Getting out of shape.

PMID- 12181547
TI  - Mass tool for diagnosis.

PMID- 12181548
TI  - Cell motility: braking WAVEs.

PMID- 12181549
TI  - Mind the double gap.

PMID- 12181551
TI  - Breaking plates.

PMID- 12181550
TI  - Signal transduction: positive feedback from coffee.

PMID- 12181552
TI  - Developmental biology: signalling legacies.

PMID- 12181553
TI  - Vote for Little Higgs.

PMID- 12181554
TI  - Scratching the Bose surface.

PMID- 12181555
TI  - Muscle regulator goes the distance.

PMID- 12181556
TI  - Surprising strength of silkworm silk.
AB  - Commercial silkworm silk is presumed to be much weaker and less extensible than
      spider dragline silk, which has been hailed as a 'super-fibre'. But we show here
      that the mechanical properties of silkworm silks can approach those of spider
      dragline silk when reeled under controlled conditions. We suggest that silkworms
      might be able to produce threads that compare well with spider silk by changing
      their spinning habits, rather than by having their silk genes altered.

PMID- 12181557
TI  - Thermoregulation in a parasite's life cycle.
AB  - The life cycle of the malaria parasite Plasmodium falciparum goes through three
      developmental stages (schizogony, gametogony and sporogony), each of which
      presents different environmental constraints that must be met by an adaptive
      response in the parasite. Here we show that thermoregulation, in which the
      transcription of select RNAs is upregulated at cooler temperatures, is crucial to
      the developmental transition that occurs during the transmission of P. falciparum
      from human to mosquito. Our findings offer new insight into how the malaria
      parasite senses and reacts to its environment.

PMID- 12181559
TI  - Macroscopically ordered state in an exciton system.
AB  - There is a rich variety of quantum liquids -- such as superconductors, liquid
      helium and atom Bose-Einstein condensates -- that exhibit macroscopic coherence
      in the form of ordered arrays of vortices. Experimental observation of a
      macroscopically ordered electronic state in semiconductors has, however, remained
      a challenging and relatively unexplored problem. A promising approach for the
      realization of such a state is to use excitons, bound pairs of electrons and
      holes that can form in semiconductor systems. At low densities, excitons are Bose
      particles, and at low temperatures, of the order of a few kelvin, excitons can
      form a quantum liquid -- that is, a statistically degenerate Bose gas or even a
      Bose-Einstein condensate. Here we report photoluminescence measurements of a
      quasi-two-dimensional exciton gas in GaAs/AlGaAs coupled quantum wells and the
      observation of a macroscopically ordered exciton state. Our spatially resolved
      measurements reveal fragmentation of the ring-shaped emission pattern into
      circular structures that form periodic arrays over lengths up to 1 mm.

PMID- 12181560
TI  - Long-range transport in excitonic dark states in coupled quantum wells.
AB  - During the past ten years, coupled quantum wells have emerged as a promising
      system for experiments on Bose condensation of excitons, with numerous
      theoretical and experimental studies aimed at the demonstration of this effect.
      One of the issues driving these studies is the possibility of long-range coherent
      transport of excitons. Excitons in quantum wells typically diffuse only a few
      micrometres from the spot where they are generated by a laser pulse; their
      diffusion is limited by their lifetime (typically a few nanoseconds) and by
      scattering due to disorder in the well structure. Here we report
      photoluminescence measurements of InGaAs quantum wells and the observation of an
      effect by which luminescence from excitons appears hundreds of micrometres away
      from the laser excitation spot. This luminescence appears as a ring around the
      laser spot; almost none appears in the region between the laser spot and the
      ring. This implies that the excitons must travel in a dark state until they reach
      some critical distance, at which they collectively revert to luminescing states.
      It is unclear whether this effect is related to macroscopic coherence caused by
      Bose condensation of excitons.

PMID- 12181561
TI  - The origin of the anomalous superconducting properties of MgB(2).
AB  - Magnesium diboride differs from ordinary metallic superconductors in several
      important ways, including the failure of conventional models to predict
      accurately its unusually high transition temperature, the effects of isotope
      substitution on the critical transition temperature, and its anomalous specific
      heat. A detailed examination of the energy associated with the formation of
      charge-carrying pairs, referred to as the 'superconducting energy gap', should
      clarify why MgB(2) is different. Some early experimental studies have indicated
      that MgB(2) has multiple gaps, but past theoretical studies have not explained
      from first principles the origin of these gaps and their effects. Here we report
      an ab initio calculation of the superconducting gaps in MgB(2) and their effects
      on measurable quantities. An important feature is that the electronic states
      dominated by orbitals in the boron plane couple strongly to specific phonon
      modes, making pair formation favourable. This explains the high transition
      temperature, the anomalous structure in the specific heat, and the existence of
      multiple gaps in this material. Our analysis suggests comparable or higher
      transition temperatures may result in layered materials based on B, C and N with
      partially filled planar orbitals.

PMID- 12181558
TI  - A physical map of the mouse genome.
AB  - A physical map of a genome is an essential guide for navigation, allowing the
      location of any gene or other landmark in the chromosomal DNA. We have
      constructed a physical map of the mouse genome that contains 296 contigs of
      overlapping bacterial clones and 16,992 unique markers. The mouse contigs were
      aligned to the human genome sequence on the basis of 51,486 homology matches,
      thus enabling use of the conserved synteny (correspondence between chromosome
      blocks) of the two genomes to accelerate construction of the mouse map. The map
      provides a framework for assembly of whole-genome shotgun sequence data, and a
      tile path of clones for generation of the reference sequence. Definition of the
      human-mouse alignment at this level of resolution enables identification of a
      mouse clone that corresponds to almost any position in the human genome. The
      human sequence may be used to facilitate construction of other mammalian genome
      maps using the same strategy.

PMID- 12181562
TI  - The influence of a chemical boundary layer on the fixity, spacing and lifetime of
      mantle plumes.
AB  - Seismological observations provide evidence that the lowermost mantle contains
      superposed thermal and compositional boundary layers that are laterally
      heterogeneous. Whereas the thermal boundary layer forms as a consequence of the
      heat flux from the Earth's outer core, the origin of an (intrinsically dense)
      chemical boundary layer remains uncertain. Observed zones of 'ultra-low' seismic
      velocity suggest that this dense layer may contain metals or partial melt, and
      thus it is reasonable to expect the dense layer to have a relatively low
      viscosity. Also, it is thought that instabilities in the thermal boundary layer
      could lead to the intermittent formation and rise of mantle plumes. Flow into
      ascending plumes can deform the dense layer, leading, in turn, to its gradual
      entrainment. Here we use analogue experiments to show that the presence of a
      dense layer at the bottom of the mantle induces lateral variations in temperature
      and viscosity that, in turn, determine the location and dynamics of mantle
      plumes. A dense layer causes mantle plumes to become spatially fixed, and the
      entrainment of low-viscosity fluid enables plumes to persist within the Earth for
      hundreds of millions of years.

PMID- 12181563
TI  - Seismic evidence for catastrophic slab loss beneath Kamchatka.
AB  - In the northwest Pacific Ocean, a sharp corner in the boundary between the
      Pacific plate and the North American plate joins a subduction zone running along
      the southern half of the Kamchatka peninsula with a region of transcurrent motion
      along the western Aleutian arc. Here we present images of the seismic structure
      beneath the Aleutian-Kamchatka junction and the surrounding region, indicating
      that: the subducting Pacific lithosphere terminates at the Aleutian-Kamchatka
      junction; no relict slab underlies the extinct northern Kamchatka volcanic arc;
      and the upper mantle beneath northern Kamchatka has unusually slow shear
      wavespeeds. From the tectonic and volcanic evolution of Kamchatka over the past
      10 Myr (refs 3-5) we infer that at least two episodes of catastrophic slab loss
      have occurred. About 5 to 10 Myr ago, catastrophic slab loss shut down island-arc
      volcanic activity north of the Aleutian-Kamchatka junction. A later episode of
      slab loss, since about 2 Myr ago, seems to be related to the activity of the
      world's most productive island-arc volcano, Klyuchevskoy. Removal of lithospheric
      mantle is commonly discussed in the context of a continental collision, but our
      findings imply that episodes of slab detachment and loss are also important
      agents in the evolution of oceanic convergent margins.

PMID- 12181564
TI  - A primitive fish close to the common ancestor of tetrapods and lungfish.
AB  - The relationship of the three living groups of sarcopterygians or lobe-finned
      fish (tetrapods, lungfish and coelacanths) has been a matter of debate. Although
      opinions still differ, most recent phylogenies suggest that tetrapods are more
      closely related to lungfish than to coelacanths. However, no previously known
      fossil taxon exhibits a concrete character combination approximating the
      condition expected in the last common ancestor of tetrapods and lungfish -- and
      it is still poorly understood how early sarcopterygians diverged into the
      tetrapod lineage (Tetrapodomorpha) and the lungfish lineage (Dipnomorpha). Here
      we describe a fossil sarcopterygian fish, Styloichthys changae gen. et sp. nov.,
      that possesses an eyestalk and which exhibits the character combination expected
      in a stem group close to the last common ancestor of tetrapods and lungfish.
      Styloichthys from the Lower Devonian of China bridges the morphological gap
      between stem-group sarcopterygians (Psarolepis and Achoania) and basal
      tetrapodomorphs/basal dipnomorphs. It provides information that will help in the
      study of the relationship of early sarcopterygians, and which will also help to
      resolve the tetrapod-lungfish divergence into a documented sequence of character
      acquisition.

PMID- 12181565
TI  - Increasing dominance of large lianas in Amazonian forests.
AB  - Ecological orthodoxy suggests that old-growth forests should be close to dynamic
      equilibrium, but this view has been challenged by recent findings that
      neotropical forests are accumulating carbon and biomass, possibly in response to
      the increasing atmospheric concentrations of carbon dioxide. However, it is
      unclear whether the recent increase in tree biomass has been accompanied by a
      shift in community composition. Such changes could reduce or enhance the carbon
      storage potential of old-growth forests in the long term. Here we show that non
      fragmented Amazon forests are experiencing a concerted increase in the density,
      basal area and mean size of woody climbing plants (lianas). Over the last two
      decades of the twentieth century the dominance of large lianas relative to trees
      has increased by 1.7-4.6% a year. Lianas enhance tree mortality and suppress tree
      growth, so their rapid increase implies that the tropical terrestrial carbon sink
      may shut down sooner than current models suggest. Predictions of future tropical
      carbon fluxes will need to account for the changing composition and dynamics of
      supposedly undisturbed forests.

PMID- 12181566
TI  - Involvement of DARPP-32 phosphorylation in the stimulant action of caffeine.
AB  - Caffeine has been imbibed since ancient times in tea and coffee, and more
      recently in colas. Caffeine owes its psychostimulant action to a blockade of
      adenosine A(2A) receptors, but little is known about its intracellular mechanism
      of action. Here we show that the stimulatory effect of caffeine on motor activity
      in mice was greatly reduced following genetic deletion of DARPP-32 (dopamine- and
      cyclic AMP-regulated phosphoprotein of relative molecular mass 32,000). Results
      virtually identical to those seen with caffeine were obtained with the selective
      A(2A) antagonist SCH 58261. The depressant effect of the A(2A) receptor agonist,
      CGS 21680, on motor activity was also greatly attenuated in DARPP-32 knockout
      mice. In support of a role for DARPP-32 in the action of caffeine, we found that,
      in striata of intact mice, caffeine increased the state of phosphorylation of
      DARPP-32 at Thr 75. Caffeine increased Thr 75 phosphorylation through inhibition
      of PP-2A-catalysed dephosphorylation, rather than through stimulation of cyclin
      dependent kinase 5 (Cdk5)-catalysed phosphorylation, of this residue. Together,
      these studies demonstrate the involvement of DARPP-32 and its
      phosphorylation/dephosphorylation in the stimulant action of caffeine.

PMID- 12181567
TI  - Sperm from neonatal mammalian testes grafted in mice.
AB  - Spermatogenesis is a productive and highly organized process that generates
      virtually unlimited numbers of sperm during adulthood. Continuous proliferation
      and differentiation of germ cells occur in a delicate balance with other
      testicular compartments, especially the supporting Sertoli cells. Many complex
      aspects of testis function in humans and large animals have remained elusive
      because of a lack of suitable in vitro or in vivo models. Germ cell
      transplantation has produced complete donor-derived spermatogenesis in rodents
      but not in other mammalian species. Production of sperm in grafted tissue from
      immature mammalian testes and across species has not yet been accomplished. Here
      we report the establishment of complete spermatogenesis by grafting testis tissue
      from newborn mice, pigs or goats into mouse hosts. This approach maintains
      structural integrity and provides the accessibility that is essential for
      studying and manipulating the function of testes and for preserving the male germ
      line. Our results indicate that this approach is applicable to diverse mammalian
      species.

PMID- 12181568
TI  - Distalization of the Drosophila leg by graded EGF-receptor activity.
AB  - Arthropods and higher vertebrates both possess appendages, but these are
      morphologically distinct and the molecular mechanisms regulating patterning along
      their proximodistal axis (base to tip) are thought to be quite different. In
      Drosophila, gene expression along this axis is thought to be controlled primarily
      by a combination of transforming growth factor-beta (TGF-beta) and Wnt signalling
      from sources of ligands, Decapentaplegic (Dpp) and Wingless (Wg), in dorsal and
      ventral stripes, respectively. In vertebrates, however, proximodistal patterning
      is regulated by receptor tyrosine kinase (RTK) activity from a source of ligands,
      fibroblast growth factors (FGFs), at the tip of the limb bud. Here I revise our
      understanding of limb development in flies and show that the distal region is
      actually patterned by a distal-to-proximal gradient of RTK activity, established
      by a source of epidermal growth factor (EGF)-related ligands at the presumptive
      tip. This similarity between proximodistal patterning in vertebrates and flies
      supports previous suggestions of an evolutionary relationship between
      appendages/body-wall outgrowths in animals.

PMID- 12181569
TI  - Synthetic GPI as a candidate anti-toxic vaccine in a model of malaria.
AB  - The malaria parasite Plasmodium falciparum infects 5-10% of the world's
      population and kills two million people annually. Fatalities are thought to
      result in part from pathological reactions initiated by a malarial toxin.
      Glycosylphosphatidylinositol (GPI) originating from the parasite has the
      properties predicted of a toxin; however, a requirement for toxins in general and
      GPI in particular in malarial pathogenesis and fatality remains unproven. As anti
      toxic vaccines can be highly effective public health tools, we sought to
      determine whether anti-GPI vaccination could prevent pathology and fatalities in
      the Plasmodium berghei/rodent model of severe malaria. The P. falciparum GPI
      glycan of the sequence NH(2)-CH(2)-CH(2)-PO(4)-(Man alpha 1-2)6Man alpha 1-2Man
      alpha 1-6Man alpha 1-4GlcNH(2)alpha 1-6myo-inositol-1,2-cyclic-phosphate was
      chemically synthesized, conjugated to carriers, and used to immunize mice.
      Recipients were substantially protected against malarial acidosis, pulmonary
      oedema, cerebral syndrome and fatality. Anti-GPI antibodies neutralized pro
      inflammatory activity by P. falciparum in vitro. Thus, we show that GPI is a
      significant pro-inflammatory endotoxin of parasitic origin, and that several
      disease parameters in malarious mice are toxin-dependent. GPI may contribute to
      pathogenesis and fatalities in humans. Synthetic GPI is therefore a prototype
      carbohydrate anti-toxic vaccine against malaria.

PMID- 12181570
TI  - Mechanism of regulation of WAVE1-induced actin nucleation by Rac1 and Nck.
AB  - Rac signalling to actin -- a pathway that is thought to be mediated by the
      protein Scar/WAVE (WASP (Wiskott-Aldrich syndrome protein)-family verprolin
      homologous protein -- has a principal role in cell motility. In an analogous
      pathway, direct interaction of Cdc42 with the related protein N-WASP stimulates
      actin polymerization. For the Rac-WAVE pathway, no such direct interaction has
      been identified. Here we report a mechanism by which Rac and the adapter protein
      Nck activate actin nucleation through WAVE1. WAVE1 exists in a heterotetrameric
      complex that includes orthologues of human PIR121 (p53-inducible messenger RNA
      with a relative molecular mass (M(r)) of 140,000), Nap125 (NCK-associated protein
      with an M(r) of 125,000) and HSPC300. Whereas recombinant WAVE1 is constitutively
      active, the WAVE1 complex is inactive. We therefore propose that Rac1 and Nck
      cause dissociation of the WAVE1 complex, which releases active WAVE1-HSPC300 and
      leads to actin nucleation.

PMID- 12181571
TI  - Modulation of an RNA-binding protein by abscisic-acid-activated protein kinase.
AB  - Protein kinases are involved in stress signalling in both plant and animal
      systems. The hormone abscisic acid mediates the responses of plants to stresses
      such as drought, salinity and cold. Abscisic-acid-activated protein kinase (AAPK 
      - found in guard cells, which control stomatal pores -- has been shown to
      regulate plasma membrane ion channels. Here we show that AAPK-interacting protein
      1 (AKIP1), with sequence homology to heterogeneous nuclear RNA-binding protein
      A/B, is a substrate of AAPK. AAPK-dependent phosphorylation is required for the
      interaction of AKIP1 with messenger RNA that encodes dehydrin, a protein
      implicated in cell protection under stress conditions. AAPK and AKIP1 are present
      in the guard-cell nucleus, and in vivo treatment of such cells with abscisic acid
      enhances the partitioning of AKIP1 into subnuclear foci which are reminiscent of
      nuclear speckles. These results show that phosphorylation-regulated RNA target
      discrimination by heterogeneous nuclear RNA-binding proteins may be a general
      phenomenon in eukaryotes, and implicate a plant hormone in the regulation of
      protein dynamics during rapid subnuclear reorganization.

PMID- 12181575
TI  - [ENDOSCOPIC POLYPECTOMY MODIFIES COLORECTAL CANCER PROGNOSIS]

PMID- 12181572
TI  - Transcriptional co-activator PGC-1 alpha drives the formation of slow-twitch
      muscle fibres.
AB  - The biochemical basis for the regulation of fibre-type determination in skeletal
      muscle is not well understood. In addition to the expression of particular
      myofibrillar proteins, type I (slow-twitch) fibres are much higher in
      mitochondrial content and are more dependent on oxidative metabolism than type II
      (fast-twitch) fibres. We have previously identified a transcriptional co
      activator, peroxisome-proliferator-activated receptor-gamma co-activator-1 (PGC-1
      alpha), which is expressed in several tissues including brown fat and skeletal
      muscle, and that activates mitochondrial biogenesis and oxidative metabolism. We
      show here that PGC-1 alpha is expressed preferentially in muscle enriched in type
      I fibres. When PGC-1 alpha is expressed at physiological levels in transgenic
      mice driven by a muscle creatine kinase (MCK) promoter, a fibre type conversion
      is observed: muscles normally rich in type II fibres are redder and activate
      genes of mitochondrial oxidative metabolism. Notably, putative type II muscles
      from PGC-1 alpha transgenic mice also express proteins characteristic of type I
      fibres, such as troponin I (slow) and myoglobin, and show a much greater
      resistance to electrically stimulated fatigue. Using fibre-type-specific
      promoters, we show in cultured muscle cells that PGC-1 alpha activates
      transcription in cooperation with Mef2 proteins and serves as a target for
      calcineurin signalling, which has been implicated in slow fibre gene expression.
      These data indicate that PGC-1 alpha is a principal factor regulating muscle
      fibre type determination.

PMID- 12181576
TI  - [COLORECTAL MALIGNANT POLYP: RESULTS OF TREATMENT AND FOLLOW-UP]
AB  - We present the results of the treatment and five year or more follow-up of
      patients with malignant polyp removed by colonoscopic polypectomy. They were 17
      male and 9 female, between 25-85 years old, mean 60.4 years. 29 malignant polyps
      removed had well differentiated or moderated well differentiated adenocarcinoma;
      10 patients had 36 synchronous lesions, 77% of them were adenomas. 22 patients
      had only polypectomy, and 4 polypectomy and colon resection, whose surgical
      specimen was tumor free in the site of polypectomy, without metastatic nodes.
      During the follow-up, two patients died of other causes than malignant polyp; one
      did not return; and 23 remain free of tumor. Colonoscopic polypectomy can be an
      excellent treatment for malignant colorectal polyp if the risk factors 
      endoscopic, pathological of the invasive carcinoma and the general clinical
      conditions of patients- are strictly applied.

PMID- 12181577
TI  - [ESOPHAGEAL STENOSIS IN CHILDREN: MEDICAL TREATMENT EXPERIENCE]
AB  - We present a retrospective evaluation of our experience in the period that goes
      from January 1992 to December 1998, clinical records of 58 patients ages from 2
      months old to 15 years, male and female, who were treated at the GI service of
      Instituto de Salud del Ni o, were reviewed. All of them had esophageal stenosis
      and were included in the Esophageal Dilatation Program with Savary-Gilliard
      bougies. The causes of Esophageal Stenosis in the study were: Caustic agents
      37.9%, gastro esophageal reflux (GER) 20.7%, surgery sequela 19.0%, related to
      esophageal esclerotherapy 12.1%, foreign body itself or maneuvers to retrieve
      them 8.6%, stomach adenocarcinoma invading the esophagus. Patients were
      classified in three groups: Group 1: stenosis due to caustic agents Group 2:
      stenosis due to GER Group 3: The remaining causes mentioned above., In each the
      following was calculated: the arithmetical media, the range of dilatations
      sessions and the total number of them. The higher figures took place in group 1.
      So we conclude that the number of sessions is directly related with the cause of
      the stenosis, requiring more number of dilatations to get a better response.
      Finally the response to treatment is evaluated considering a good response in
      72.4%. A mild response in 15.5% and therapeutic failure in 12.1% of patients. The
      rate of complications was 10.3 per patient and 1.1 in relation to the total
      number of dilatation sessions. The main complications were: gastric perforation,
      duodenal perforation, pneumomediastinum, esophago-tracheal fistulae andi
      pseudodiverticulum formation, with resolution as seen in posterior controls.
      These complications occured after the proceeding took place. The treatment was
      installed according to each case. The patients with duodenal perforation died. We
      conclude that esophageal dilatations in infants with esophageal stenosis, of
      different ethiology, are secure and efficient.

PMID- 12181579
TI  - [OMEPRAZOL VS RANITIDINE IN UPPER DIGESTIVE BLEEDING]
AB  - Pectic ulcer is the most frequent cause of gastrointestinal bleeding. The
      homeostatic mechanism of bleeding, and coagulation, does not happen with values
      of pH less than 5,0. Therefore neutralization of gastric acidity (pH more than
      5,0) is a recourse of control, improve the evolution and healing of peptic ulcer
      and to avoid a new bleeding. The aim of this study was to compare the results of
      treatment with omeprazole and ranitidine, in 57 patients admitted at emergency
      room of the Hospital Central de la Polic a Nacional del Per with endoscopic
      diagnosis of peptic ulcer, using Forrest classification. Patients received
      omeprazole 40 mg in bolus IV, followed by continuos infusion of 8 mg/hour for 72
      hours (group A) or ranitidine 50 mg IV each 8 hours for 72 hours (group B). A new
      endoscopy was made 72 hours after admission demostrated a succesful therapy in
      both group. Bleeding stopped in 26/27 patients in group A (96,2%) and in 23/30
      patients in group B (76,6%) (p<0,05). The results of this study show that the
      omeprazole IV is more effective than ranitidine IV in the control of UGB because
      of peptic ulcer and provides a faster healing.

PMID- 12181580
TI  - [ALTERNATIVES IN THE TREATMENT OF CHRONIC CONSTIPATION]
AB  - This article briefly reviews epidemiological, patophysiological and definition
      aspects of chronic constipation. Additionally, treatment of constipation
      regarding to general an specific measures, including several types of laxatives
      and presenting the alternative use of combined fiber and Senna, is discussed.

PMID- 12181578
TI  - [ENTERAL NUTRITION IN PERU]
AB  - Drawbacks of Nutritional Support diffusion in Peru are presented within current
      Latin-American technological reality. That reality is compared to widespread use
      of antibiotic therapy versus a marked lack of use of Nutritional Support. Those
      factors are against immunity of seriously compromised patients as Enteral
      Nutrition has positive effects on a patient s immunity.Four patients treated with
      three kinds of enteral formulas during a prospective study serve as examples to
      show the suitable consequences of using Enteral Nutrition and why Nutritional
      Support should be legally enforced and regulated in Peru.

PMID- 12181581
TI  - [HEPATIC HYDATIC CYST ASSOCIATED WITH PORTAL HYPERTENSION]
AB  - We report the case of a 26-year-old woman from Cerro of Pasco - Per , with
      hydatid cyst in the liver associated with portal hypertension. We know that the
      echinococcosis in the liver is usually asymptomatic, although can produce
      clinical features that depend of the size and localization in the liver. The
      clinical, radiological and endoscopic findings are presented, due to the uncommon
      presentation and the few cases reported in the literature about this asociation

PMID- 12181582
TI  - [SMALL BOWELL LIPOMA CAUSING INTUSSUSCEPTION IN AN ADULT]
AB  - Primary or metastatic neoplasms of the small bowel are rare. The most common
      cause of intestinal intussusceptionin adults are tumors of the small bowel. The
      intraluminal lesion alters the normal peristalsis of the intestine and permits
      the displacement of the proximal intestine to the interior of a segment of the
      distal intestine generally fixed. The preoperative diagnosis is difficult and
      computed tomography and intestinal barium are the most useful studies in order to
      define this entity. The management is surgical and consists in the reduction of
      the affected segment and the surgical resection with margin of mesentery. The
      prognosis correlates with the result of the histopathological study of the
      original tumor. The present study analyzes a case of lipoma of small bowel
      causing intussusception and intestinal occlusion. At laparotomy an ileocecal
      intussusception caused by an intraluminal tumor in the terminal ileon was
      evidenced, performing right hemicolectomy and end- to- end ileotransverse
      colostomy. The microscopic study revealed a lipoma of ileum.

PMID- 12181583
TI  - [ANISAKIASIS. REPORT OF A CASE AND REVIEW OF THE LITERATURE]
AB  - We present the case of a 38 year-old woman, who attended the Gastroenterology
      Service of a private hospital in Lima, complaining of a one week history of
      retroesternal "burning" sensation and mild, sporadic right lower quadrant
      abdominal pain. Laboratory test within normal limits were obtained and an upper
      endoscopic study was done. A white, mobile, 30 mm length parasite found attached
      to the gastric mucosa. Which was removed and identified as Anisakis spp. Taking
      into account how unusual is the report of this type of findings, the authors
      decided to review the literature and present it to the medical community. We
      suspect this parasitosis is subregistered in our country.

PMID- 12181584
TI  - Signal detection theory, detectability and stochastic resonance effects.
AB  - Stochastic resonance is a phenomenon in which the performance of certain non
      linear detectors can be enhanced by the addition of appropriate levels of random
      noise. Signal detection theory offers a powerful tool for analysing this type of
      system, through an ability to separate detection processes into reception and
      classification, with the former generally being linear and the latter always non
      linear. Through appropriate measures of signal detectability it is possible to
      decide whether a local improvement in detection via stochastic resonance occurs
      due to the non-linear effects of the classification process. In this case,
      improvement of detection through the addition of noise can never improve
      detection beyond that of a corresponding adaptive system. Signal detection and
      stochastic resonance is investigated in several integrate-and-fire neuron models.
      It is demonstrated that the stochastic resonance observed in spiking models is
      caused by non-linear properties of the spike-generation process itself. The true
      detectability of the signal, as seen by the receiver part of the spiking neuron
      (the integrator part), decreases monotonically with input noise level for all
      signal and noise intensities.

PMID- 12181585
TI  - Stochastic resonance in psychophysics and in animal behavior.
AB  - A recent analysis of the energy detector model in sensory psychophysics concluded
      that stochastic resonance does not occur in a measure of signal detectability (
      d'), but can occur in a percent-correct measure of performance as an
      epiphenomenon of nonoptimal criterion placement [Tougaard (2000) Biol Cybern 83:
      471-480]. When generalized to signal detection in sensory systems in general,
      this conclusion is a serious challenge to the idea that stochastic resonance
      could play a significant role in sensory processing in humans and other animals.
      It also seems to be inconsistent with recent demonstrations of stochastic
      resonance in sensory systems of both nonhuman animals and humans using measures
      of system performance such as signal-to-noise ratio of power spectral densities
      and percent-correct detections in a two-interval forced-choice paradigm, both
      closely related to d'. In this paper we address this apparent dilemma by
      discussing several models of how stochastic resonance can arise in signal
      detection systems, including especially those that implement a "soft threshold"
      at the input transform stage. One example involves redefining d' for energy
      increments in terms of parameters of the spike-count distribution of FitzHugh
      Nagumo neurons. Another involves a Poisson spike generator that receives an
      exponentially transformed noisy periodic signal. In this case it can be shown
      that the signal-to-noise ratio of the power spectral density at the signal
      frequency, which exhibits stochastic resonance, is proportional to d'. Finally, a
      variant of d' is shown to exhibit stochastic resonance when calculated directly
      from the distributions of power spectral densities at the signal frequency
      resulting from transformation of noise alone and a noisy signal by a sufficiently
      steep nonlinear response function. All of these examples, and others from the
      literature, imply that stochastic resonance is more than an epiphenomenon,
      although significant limitations to the extent to which adding noise can aid
      detection do exist.

PMID- 12181586
TI  - Desynchronization of brain rhythms with soft phase-resetting techniques.
AB  - Composite stimulation techniques are presented here which are based on a soft
      (i.e., slow and mild) reset. They effectively desynchronize a cluster of globally
      coupled phase oscillators in the presence of noise. A composite stimulus contains
      two qualitatively different stimuli. The first stimulus is either a periodic
      pulse train or a smooth, sinusoidal periodic stimulus with an entraining
      frequency close to the cluster's natural frequency. In the course of several
      periods of the entrainment, the cluster's dynamics is reset (restarted),
      independently of its initial dynamic state. The second stimulus, a single pulse,
      is administered with a fixed delay after the first stimulus in order to
      desynchronize the cluster by hitting it in a vulnerable state. The incoherent
      state is unstable, and thus the desynchronized cluster starts to resynchronize.
      Nevertheless, resynchronization can effectively be blocked by repeatedly
      delivering the same composite stimulus. Previously designed stimulation
      techniques essentially rely on a hard (i.e., abrupt) reset. With the composite
      stimulation techniques based on a soft reset, an effective desynchronization can
      be achieved even if strong, quickly resetting stimuli are not available or not
      tolerated. Accordingly, the soft methods are very promising for applications in
      biology and medicine requiring mild stimulation. In particular, it can be applied
      to effectively maintain incoherency in a population of oscillatory neurons which
      try to synchronize their firing. Accordingly, it is explained how to use the soft
      techniques for (i). an improved, milder, and demand-controlled deep brain
      stimulation for patients with Parkinson's disease or essential tremor, and for
      (ii). selectively blocking gamma activity in order to manipulate visual binding.

PMID- 12181587
TI  - Schema design and implementation of the grasp-related mirror neuron system.
AB  - Mirror neurons within a monkey's premotor area F5 fire not only when the monkey
      performs a certain class of actions but also when the monkey observes another
      monkey (or the experimenter) perform a similar action. It has thus been argued
      that these neurons are crucial for understanding of actions by others. We offer
      the hand-state hypothesis as a new explanation of the evolution of this
      capability: the basic functionality of the F5 mirror system is to elaborate the
      appropriate feedback - what we call the hand state - for opposition-space based
      control of manual grasping of an object. Given this functionality, the social
      role of the F5 mirror system in understanding the actions of others may be seen
      as an exaptation gained by generalizing from one's own hand to an other's hand.
      In other words, mirror neurons first evolved to augment the "canonical" F5
      neurons (active during self-movement based on observation of an object) by
      providing visual feedback on "hand state," relating the shape of the hand to the
      shape of the object. We then introduce the MNS1 (mirror neuron system 1) model of
      F5 and related brain regions. The existing Fagg-Arbib-Rizzolatti-Sakata model
      represents circuitry for visually guided grasping of objects, linking the
      anterior intraparietal area (AIP) with F5 canonical neurons. The MNS1 model
      extends the AIP visual pathway by also modeling pathways, directed toward F5
      mirror neurons, which match arm-hand trajectories to the affordances and location
      of a potential target object. We present the basic schemas for the MNS1 model,
      then aggregate them into three "grand schemas" - visual analysis of hand state,
      reach and grasp, and the core mirror circuit - for each of which we present a
      useful implementation (a non-neural visual processing system, a multijoint 3-D
      kinematics simulator, and a learning neural network, respectively). With this
      implementation we show how the mirror system may learn to recognize actions
      already in the repertoire of the F5 canonical neurons. We show that the
      connectivity pattern of mirror neuron circuitry can be established through
      training, and that the resultant network can exhibit a range of novel,
      physiologically interesting behaviors during the process of action recognition.
      We train the system on the basis of final grasp but then observe the whole time
      course of mirror neuron activity, yielding predictions for neurophysiological
      experiments under conditions of spatial perturbation, altered kinematics, and
      ambiguous grasp execution which highlight the importance of the timing of mirror
      neuron activity.

PMID- 12181588
TI  - Perception--action coupling model for human locomotor pointing.
AB  - How do humans achieve the precise positioning of the feet during walking, for
      example, to reach the first step of a stairway? We addressed this question at the
      visuomotor integration level. Based on the optical specification of the required
      adaptation, a dynamical system model of the visuomotor control of human locomotor
      pointing was devised for the positioning of a foot on a visible target on the
      floor during walking. Visuomotor integration consists of directly linking optical
      information to a motor command that specifically modulates step length in
      accordance with the ongoing dynamics of locomotor pattern generation. The
      adaptation of locomotion emerges from a perception-action coupling type of
      control based on temporal information rather than on feedforward planning of
      movements. The proposed model reproduces experimental results obtained for human
      locomotor pointing.

PMID- 12181589
TI  - Augmented vasodilator response to L-arginine after coronary angioplasty may
      attenuate restenosis.
AB  - Nitric oxide (NO) plays an important role in the control of vascular tone as well
      as structure. This study examined the possibility that the extent of restenosis 3
      months after percutaneous transluminal coronary angioplasty (PTCA) might be
      correlated with the magnitude of NO production at the PTCA sites on the day
      following PTCA. In 23 consecutive patients who underwent PTCA, we examined the
      coronary artery diameter response to intracoronary administration of L-arginine
      (1 microg/kg) and isosorbide dinitrate (ISDN, 40 microg/kg) at the sites of PTCA
      (n = 25) and at untreated sites distal to the PTCA sites approximately 18 h after
      PTCA. The coronary artery diameter at the PTCA site was determined 3 months after
      PTCA in all patients. Normalized vasodilator responses to L-arginine (responses
      to L-arginine/those to ISDN) were greater at the PTCA sites than at the untreated
      sites (P = 0.05), whereas vasodilator responses to ISDN did not differ between
      the PTCA and untreated sites. These results suggest a greater production of NO at
      the PTCA sites despite presumable loss of the endothelium due to the PTCA.
      Furthermore, the magnitude of normalized vasodilator responses to L-arginine
      examined at 18 h after PTCA correlated with the coronary artery diameter 3 months
      after PTCA (r = 0.592, P = 0.002). These results suggest that augmented NO
      production after PTCA may protect against the development of coronary restenosis.
      Treatment that enhances local NO production may be clinically useful in
      preventing restenosis after PTCA.

PMID- 12181590
TI  - Assessment of right heart function in the athlete's heart.
AB  - It is known that the heart of an athlete has been physiologically adapted by
      prolonged training. There are a large number of echocardiographic studies which
      have focused on left ventricular wall thickness and dilatation, but there are few
      studies concerning right heart function in the athlete's heart. The aim of this
      study was to assess right heart function in elite athletes by conventional and
      new echocardiographic methods. The study population consisted of 36 elite highly
      trained male athletes and 16 age-matched healthy sedentary controls. Right
      atrial, right ventricular, and inferior vena cava dimensions, and pulsed Doppler
      measurements of tricuspid inflow and right ventricular outflow were obtained, and
      systolic (preejection period, ejection time, preejection time/ejection time, QV
      peak, isovolumic contraction time) and diastolic (E peak, A peak, E/A ratio,
      decelaration time, isovolumic relexation time) function parameters were measured.
      The myocardial performance index was calculated as (isovolumetric contraction
      time + isovolumetric relaxation time)/ejection time. In addition, right
      ventricular systolic and diastolic functions were determined by Pulsed wave
      tissue Doppler imaging (S, E, and A velocities) at the lateral corners of the
      tricuspid annulus. The left ventricular mass index (P < 0.005), and right atrial
      (P < 0.001), right ventricular (P < 0.001), and inferior vena cava dimensions (P
      < 0.001) were significantly greater in athletes than in controls. Tricuspid E
      peak, A peak, E/A ratio, deceleration time, isovolumic relaxation time,
      preejection period, right ventricular ejection time, preejection time/ejection
      time, isovolumic contraction time, QV peak, and myocardial performance index were
      found to be similar in athletes and in controls (P > 0.05). Systolic, early
      diastolic, and late diastolic tissue Doppler imaging velocities were not
      significantly different in athletes and controls (P > 0.05). Left ventricular
      hypertrophy (LV mass index >134 g/m2) was found in 15 of the athletes. Right
      atrial dimension was greater in the athletes with left ventricular hypertrophy
      than in those without hypertrophy (P < 0.05). All right ventricular systolic and
      diastolic echocardiographic parameters were similar in athletes with and without
      left ventricular hypertrophy (P > 0.05). The results of this study indicate that
      right ventricular systolic and diastolic functions do not deteriorate in the
      athlete's heart despite significant chamber dilatation. They suggest that these
      changes are a normal physiologic adaptation to prolonged training.

PMID- 12181592
TI  - Carbon monoxide regulates blood pressure cooperatively with nitric oxide in
      hypertensive rats.
AB  - Both carbon monoxide (CO), the product of heme oxygenase (HO), and nitric oxide
      (NO) elevate cyclic guanosine monophosphate levels in smooth muscle cells,
      leading to relaxation of the vessels. We examined the hypothesis that the effect
      of CO in regulating blood pressure could be augmented in hypertension where the
      function and/or production of NO is impaired. We used two hypertensive models, a
      spontaneously hypertensive rat (SHR), and a Wistar Kyoto rat (WKY) which was
      given the NO synthase (NOS) inhibitor N(omega)-nitro- L-arginine (L-NNA). In
      these hypertensive rats, we examined HO gene expression with Northern blot
      analysis, guanosine 3',5'-monophosphate (cGMP) levels with enzyme-linked
      immunosorbent assay of each organ, and the response of blood pressure to
      treatment with an HO substrate (hemin, 23 micromol/kg body weight, i.p.) or HO
      inhibitor (zinc or tin protoporphyrin-IX; ZnPP or SnPP, 50 micromol/kg body
      weight i.p. or s.c.), for 4 or 8 consecutive days with plethysmography. Northern
      blot analysis showed that HO-1 and -2 mRNA levels in the left ventricle, aorta,
      kidney, and soleus muscle in the hypertensive rats were 2-5 times higher than
      those in control normotensive WKYrats. In contrast, both HO mRNA levels in the
      gastrocnemius muscle in the hypertensive rats were similar to those in control
      WKYrats. As to whether the HO/CO system contributes to the regulation of blood
      pressure, ZnPP or SnPP increased and hemin decreased systolic blood pressure
      (SBP), respectively, in the hypertensive rats (P < 0.01), but not in WKYrats,
      accompanied with changes in cGMP in each organ of the hypertensive rats. The
      effect of CO in the regulation of blood pressure is augmented, resulting in
      increased expression of HO gene when the function and/or production of NO is
      impaired.

PMID- 12181591
TI  - The role of endothelin in oxygen-induced contraction of the ductus arteriosus in
      rabbit and rat fetuses.
AB  - The role of endothelin in oxygen-induced contraction remains controversial. The
      present study was designed to investigate the role of endothelin in O2-induced
      contraction in the isolated ductal preparation of rabbit and rat, using the
      endothelin receptor antagonists, bosentan (antagonist for both ET-A and ET-B
      receptors) and BQ 485 (an ET-A selective antagonist). The ductus was isolated
      from fetal rabbits at 30 days of gestation (term 31 days) and fetal rats at 21
      days of gestation (term 22 days). In the rabbit ductus with intact endothelium,
      13% of the O2-induced contraction was inhibited by bosentan and 14% by BQ 485. In
      the rabbit ductus without endothelium, bosentan did not cause significant
      inhibition of the oxygen-induced contraction. In the rat ductus with intact
      endothelium, about 44% of the O2-induced contraction was inhibited by bosentan.
      In the rat ductus without endothelium, O2-induced contraction was 20% less than
      that in the ductus with intact endothelium. In the rat ductus without
      endothelium, bosentan further decreased the oxygen-induced contraction by about
      24%. These data suggest that (1) endothelin plays a significant role in O2
      induced contraction in the isolated ductus arteriosus, (2) there is a species
      difference in the degree of contribution of endothelin to the O2-induced ductal
      contraction, and (3) there is a species difference in the degree of contribution
      of the endothelium and vascular smooth muscle cells to the release of endothelin
      from the ductus arteriosus.

PMID- 12181593
TI  - A recurrent right atrial thrombus: a suggestive sign for Behcet's disease? A case
      report.
AB  - A29-year-old woman with Behcet's disease was admitted to our cardiology
      department with a history of cough, dyspnea, and palpitation. Transthoracic and
      transesophageal echocardiography revealed a right atrial mass. She was operated
      on to remove the mass, which was shown by histopathological examination to be a
      thrombus. Three months later, echocardiography was repeated and recurrent right
      atrial thrombus was observed. Warfarin was given to the patient. One month later,
      the mass was not observed on echocardiographic examination. We report recurrent
      right atrial thrombus in a patient with Behcet's disease.

PMID- 12181594
TI  - Allograft pulmonary artery root replacement for refractory isolated pulmonic
      valve endocarditis.
AB  - A 45-year-old diabetic woman was subjected to percutaneous cardiopulmonary
      support for a life-threatening pulmonary embolism. One month later, she developed
      isolated pulmonic valve endocarditis. The causative organism was methicillin
      resistant Staphylococcus aureus. Because of the uncontrollable infection and
      residual pulmonary hypertension, she underwent pulmonary artery root replacement
      with a cryopreserved pulmonary allograft. The postoperative course was very good.
      In this case, allograft implantation with a full root played a very important
      role because this method permitted thorough resection of the infected tissues and
      reconstruction which is highly resistant to infection.

PMID- 12181595
TI  - Involvement of the coronary artery in a patient with thromboangiitis obliterans.
      A case report.
AB  - We report a case of coronary artery bypass grafting (CABG) using the left
      internal mammary artery (LIMA) and a saphenous vein graft in a 36-year-old man
      with Buerger's disease. He was hospitalized in the coronary intensive care unit
      with a diagnosis of acute myocardial infarction. His coronary angiography showed
      total occlusion of the proximal segment of the left anterior descending artery
      (LAD) and right coronary artery. Left ventricular dysfunction was detected by
      ventriculography. The patient had undergone bilateral sympathectomy of the lumbar
      branches for distal arterial occlusions due to thromboangiitis obliterans 12
      years previously. Under cardiopulmonary bypass and aortic cross-clamping, we
      performed endarterectomy and a complex bypass procedure to LAD. Aorta-right
      coronary artery bypass was also applied. A histopathological study of an
      endarterectomy specimen showed characteristic features of thromboangiitis
      obliterans. The postoperative course was uneventful and the patient was
      discharged on the ninth postoperative day.

PMID- 12181596
TI  - Spontaneous intramyocardial hematoma presenting as a rapidly expanding mass
      followed by echocardiography.
AB  - A50-year-old man with an intramyocardial mass was referred to us. He had
      undergone resection of both a coronary arterial aneurysm of unknown origin and a
      postinfarction left ventricular (LV) aneurysm 5 years before. Peak creatine
      kinase was slightly over the upper normal range, and an electrocardiogram
      revealed neither a new Q-wave nor an additional ST-segment change. Repeated two
      dimensional echocardiography indicated rapid expansion of a heterogeneous mass in
      the posterior wall of the LV. The mass was intraoperatively diagnosed as
      intramyocardial hematoma without connection to the LV cavity. Via posterolateral
      thoracotomy with partial cardiopulmonary bypass, the outer layer of the hematoma
      was completely resected, and xenopericardium was applied with a continuous suture
      to cover the space which the hematoma had occupied. The patient made an
      uneventful recovery.

PMID- 12181597
TI  - Free-floating ball thrombus in the left atrium.
AB  - Free-floating ball thrombi in the left atrium are rarely seen. They can cause
      sudden death by occluding the mitral valve. A 47-year-old female patient who
      showed signs of mitral stenosis during a physical examination and atrial
      fibrillation by electrocardiography was not administered anticoagulant therapy.
      On the transthoracic echocardiogram, a stenotic mitral valve and a floating
      mobile mass were seen inside the large left atrium. This mass was rounded (ball
      like), had smooth contours, and occasionally occluded the stenotic mitral valve.
      The patient underwent emergency surgery to remove the mass, which was later
      proven to be a thrombus pathologically. Additionally, mitral valve replacement
      was performed. The importance of anticoagulant therapy for patients with
      rheumatic mitral stenosis has been emphasized by this case.

PMID- 12181598
TI  - Multiple complex coronary plaques in a patient with acute myocardial infarction.
AB  - This report describes the case of a patient who developed acute myocardial
      infarction with ST segment elevation in anterior and inferior leads,
      simultaneously. After treatment with systemic thrombolysis, and after an initial
      short-lasting symptomatic improvement, chest pain and ST segment elevation
      recurred. Coronary angiography revealed severe complex stenotic lesions at both
      the right coronary artery and the left anterior descending (LAD) coronary artery.
      Percutaneous coronary angioplasty and stent implantation were successfully
      performed at both lesions. This case supports the concept that, at least in some
      patients, acute coronary artery disease reflects a diffuse pathophysiologic
      process that may lead to multifocal plaque instability associated with clinical
      instability at multiple sites.

PMID- 12181599
TI  - Serum lipoprotein (a) level and severity of coronary artery disease.

PMID- 12181600
TI  - Evolutionary suicide and evolution of dispersal in structured metapopulations.
AB  - We study the evolution of dispersal in a structured metapopulation model. The
      metapopulation consists of a large (infinite) number of local populations living
      in patches of habitable environment. Dispersal between patches is modelled by a
      disperser pool and individuals in transit between patches are exposed to a risk
      of mortality. Occasionally, local catastrophes eradicate a local population: all
      individuals in the affected patch die, yet the patch remains habitable. We prove
      that, in the absence of catastrophes, the strategy not to migrate is
      evolutionarily stable. Under a given set of environmental conditions, a
      metapopulation may be viable and yet selection may favor dispersal rates that
      drive the metapopulation to extinction. This phenomenon is known as evolutionary
      suicide. We show that in our model evolutionary suicide can occur for catastrophe
      rates that increase with decreasing local population size. Evolutionary suicide
      can also happen for constant catastrophe rates, if local growth within patches
      shows an Allee effect. We study the evolutionary bifurcation towards evolutionary
      suicide and show that a discontinuous transition to extinction is a necessary
      condition for evolutionary suicide to occur. In other words, if population size
      smoothly approaches zero at a boundary of viability in parameter space, this
      boundary is evolutionarily repelling and no suicide can occur.

PMID- 12181601
TI  - Evolutionary branching of dispersal strategies in structured metapopulations.
AB  - Dispersal polymorphism and evolutionary branching of dispersal strategies has
      been found in several metapopulation models. The mechanism behind those findings
      has been temporal variation caused by cyclic or chaotic local dynamics, or
      temporally and spatially varying carrying capacities. We present a new mechanism:
      spatial heterogeneity in the sense of different patch types with sufficient
      proportions, and temporal variation caused by catastrophes. The model where this
      occurs is a generalization of the model by Gyllenberg and Metz (2001). Their
      model is a size-structured metapopulation model with infinitely many identical
      patches. We present a generalized version of their metapopulation model allowing
      for different types of patches. In structured population models, defining and
      computing fitness in polymorphic situations is, in general, difficult. We present
      an efficient method, which can be applied also to other structured population or
      metapopulation models.

PMID- 12181602
TI  - The role of cell-cell interactions in a two-phase model for avascular tumour
      growth.
AB  - A two-phase model is presented to describe avascular tumour growth. Conservation
      of mass equations, including oxygen-dependent cell growth and death terms, are
      coupled with equations of momentum conservation. The cellular phase behaves as a
      viscous liquid, while the viscosity of the extracellular water manifests itself
      as an interphase drag. It is assumed that the cells become mechanically stressed
      if they are too densely packed and that the tumour will try to increase its
      volume in order to relieve such stress. By contrast, the overlapping filopodia of
      sparsely populated cells create short-range attractive effects. Finally, oxygen
      is consumed by the cells as it diffuses through the tumour. The resulting system
      of equations are reduced to three, which describe the evolution of the tumour
      cell volume fraction, the cell speed and the oxygen tension. Numerical
      simulations indicate that the tumour either evolves to a travelling wave profile,
      in which it expands at a constant rate, or it settles to a steady state, in which
      the net rates of cell proliferation and death balance. The impact of varying key
      model parameters such as cellular viscosity, interphase drag, and cellular
      tension are discussed. For example, tumours consisting of well-differentiated
      (i.e. viscous) cells are shown to grow more slowly than those consisting of
      poorly-differentiated (i.e. less viscous) cells. Analytical results for the case
      of oxygen-independent growth are also presented, and the effects of varying the
      key parameters determined (the results are in line with the numerical simulations
      of the full problem). The key results and their biological implications are then
      summarised and future model refinements discussed.

PMID- 12181603
TI  - Reaction routes in biochemical reaction systems: algebraic properties, validated
      calculation procedure and example from nucleotide metabolism.
AB  - Elementary flux modes (direct reaction routes) are minimal sets of enzymes that
      can operate at steady state, with all irreversible reactions used in the
      appropriate direction. They can be interpreted as component pathways of a
      (bio)chemical reaction network. Here, two different definitions of elementary
      modes are given and their equivalence is proved. Several algebraic properties of
      elementary modes are then presented and proved. This concerns, amongst other
      features, the minimal number of enzymes of the network not used in an elementary
      mode and the situations where irreversible reactions are replaced by reversible
      ones. Based on these properties, a refined algorithm is presented, and it is
      formally proved that this algorithm will exclusively generate all the elementary
      flux modes of an arbitrary network containing reversible or irreversible
      reactions or both. The algorithm is illustrated by a biochemical example relevant
      in nucleotide metabolism. The computer implementation in two different
      programming languages is discussed.

PMID- 12181604
TI  - Sternal fractures: retrospective analysis of 100 cases.
AB  - Isolated sternal fractures are seen with increasing frequency in road accidents,
      especially since the introduction of seatbelt legislation. The medical records of
      all our patients who were treated with a diagnosis of sternal fracture (SF) over
      the past two decades were retrospectively reviewed to determine the incidence,
      morbidity, and mortality of this entity. Between 1984 and 1998, 100 consecutive
      patients were admitted to the Department of Surge Surgery, General Hospital of
      Nikea-Piraeus, Greece, for SF. There were 72 men and 28 women ranging in age
      between 17 and 84 years. Sixty-seven patients sustained an isolated SF and the
      remaining 33 had a SF in combination with multiple injuries such as flail chest
      (n = 19), head injury (n = 18), limb fractures (n = 10), spinal fractures (n =
      4), hear contusion (n = 1), hemo-pneumothorax (n = 9), pneumothorax (n = 6),
      hemomediastinum (n = 5), and pericarditis (n = 2), among others. All patients
      with a radiological diagnosis were admitted for cardiac monitoring for at least
      24 hours. Electrocardiogram (ECG), determinations of cardiac enzyme levels such
      as lactic dehydrogenase, creatine kinase, and creatine kinase-MB, and evaluation
      by a cardiologist were routinely performed. An echocardiogram was performed as
      indicated by the cardiologist. Seven patients underwent operation, two for
      abdominal bleeding, two for chest wall and sternal stabilization, two for open
      pneumothorax, and one for massive hemothorax. Eight of our patients needed
      ventilatory support. Four of them died from respiratory insufficiency, myocardial
      infarction, and heart and lung contusion. Although an isolated SF carries a good
      prognosis, careful evaluation and clinical observation are essential.

PMID- 12181605
TI  - Quality of life, surgical outcome, and patient satisfaction three years after
      laparoscopic Nissen fundoplication.
AB  - Quality of life data and patient satisfaction are important issues in estimating
      the outcome of laparoscopic antireflux surgery (LARS). Long-term of quality of
      life assessment has not yet received wide attention. The aim of this prospective
      study was to evaluate surgical outcome, including quality of life and patient
      satisfaction, after laparoscopic "floppy" Nissen fundoplication up to 3 years
      after surgery. Between 1994 and 1996, a total of 150 consecutive patients with
      severe gastroesophageal reflux disease underwent laparoscopic "floppy" Nissen
      fundoplication. Quality of life was evaluated using the Gastrointestinal Quality
      of Life Index (GIQLI). The GIQLI questionnaire was given to the patients prior to
      surgery, and again 3 months, 1 year, and 3 years postoperatively. In addition, 24
      hour pH monitoring and esophageal manometry were performed preoperatively and at
      each follow-up date. Finally, surgical side-effects and patient satisfaction with
      the surgical outcome were evaluated 3 years after LARS. Postoperatively lower
      esophageal sphincter pressure improved significantly in all patients, whereas pH
      values showed normal data in all but 5 patients. Before surgery, all patients had
      a poor quality of life (GIQLI score, 90.1 +/- 8.9 points). Postoperatively, GIQLI
      improved significantly (p < .01) and remained stable for at least 3 years, with a
      mean value of 123.7 +/- 9.8 points. This is comparable to 122.6 +/- 8.5 points of
      healthy individuals. Ninety-eight percent of the patients rated their
      satisfaction with surgical treatment as excellent or good and would undergo
      surgery again if necessary. Nine patients suffered from minimal surgical side
      effects, but these did not significantly impair their quality of life.
      Laparoscopic reoperation was performed in 2 patients 3 months after initial
      surgery because of severe dysphagia. Both patients were free of symptoms 3 years
      after surgery. The efficacy and long-term outcome of treatment of
      gastroesophageal reflux disease with laparoscopic "floppy" Nissen fundoplication
      can be evaluated by objective testing, but also with subjective judgment of the
      patient, including quality of life assessment.

PMID- 12181606
TI  - Harbinger or hermit? Pancreatic anatomy and surgery through the ages--part 1.

PMID- 12181607
TI  - Relationships between gastric development and anatomic bases of radical surgery
      for cancer.
AB  - The aim of this study was to determine with all possible accuracy the processes
      of embryologic development of the stomach and its lymphatics in order to confirm
      their supposed link with the modern anatomic bases of gastric cancer surgery. The
      knowledge of the anatomic behavior of the peritoneal folds and of the lymphatic
      drainage of the stomach is, in fact, considered the essential basis for the
      comprehension of the oncologic dissection of the stomach. The study was based on
      reconstruction of serial histologic sections of 9 human embryos and 8 human
      fetuses regarding the mesogastric area, as well as anatomic microdissection of 2
      9-month fetuses. The proximal part of the stomach is not involved in the rotation
      mechanism of the other portions; the lesser sac development follows cranial
      migration of the spleen; the cardiac (pars cardiaca gastris) area is in
      continuity with the zone of paraaortic lymph node development; lateral and
      posterior lymph nodes of the hepatoduodenal ligament do not take origin in the
      dorsal mesogastrium: they develop together with the common bile duct and the
      ventral pancreas inside the mesoduodenum; the fusion of the dorsal mesogastrium
      and the gastric fundus with the posterior abdominal wall appears late in
      development. The embryologic study of the mesogastric area clarifies the real
      mechanism of development of the stomach and its lymphatic pathways with some
      differences from classic reports; these results agree with the more recent
      modification of the lymph nodes classification used in the radical treatment of
      gastric cancer.

PMID- 12181608
TI  - Dehydroepiandrosterone sulfate and growth axis hormones in patients after
      surgery.
AB  - We selected 38 patients scheduled for cholecystectomy and studied their serum
      concentrations of dehydroepiandrosterone (DHEA) and growth axis hormones [growth
      hormone/insulin-like growth factor-1 (GH/IGF-1)]. We aimed to determine whether
      alterations in these concentrations resulted from surgical stress or, on the
      contrary, preceded surgery and were themselves a cause of chronic diseases that
      reduce life expectancy. We measured the serum concentrations of DHEA sulfate
      (DHEA-S), ACTH, cortisol, human GH (hGH), IGF-1, and IGF-1 binding protein-3
      (IGFBP-3) preoperatively and then 2 and 7 days after surgery; we also compared
      the preoperative findings with those of a healthy control group. The results were
      analyzed by gender because DHEA and GH/IGF-1 are known to present sexual
      dimorphism. There were no significant differences between the preoperative and
      control results for any of the parameters studied. We found a significant
      reduction in the concentrations of DHEA-S and IGF-1 on days 2 and 7 after surgery
      versus the preoperative values. We conclude that the decrease in DHEA-S in
      patients after surgery is a result of surgical trauma and does not precede
      surgical stress. The decrease in hormone levels observed in patients with chronic
      disease may therefore be a result, not a cause, of disease, as some have claimed.
      Further studies with a later endpoint would be of interest to assess any
      subsequent return of DHEA-S levels to baseline measurements.

PMID- 12181610
TI  - Adenosine 5'-monophosphate is a selective inhibitor of the brown adipocyte
      nonselective cation channel.
AB  - Calcium-activated nonselective cation channels (NSC(Ca)) in brown adipocytes are
      inhibited by several nucleotides acting on the cytosolic side of the membrane. We
      used excised inside-out patches from rat brown adipocytes to identify important
      nucleotide structures for NSC-channel inhibition. We found that 100 microM 5'-AMP
      inhibited NSC-channel activity more than did ATP or ADP. Adenosine was a weak
      inhibitor, whereas adenine and ribose-5-phosphate had no effect. The channel
      activity was effectively blocked by 10 microM AMP, but it was unaffected by 10
      microM cAMP, CMP, GMP, IMP, TMP or UMP. Dose-response studies yielded IC(50)
      values of 4 microM for AMP and 32 microM for cAMP. dAMP was as effective as AMP,
      but all 5'-phosphate group modifications on AMP dramatically lowered the
      inhibitory effect. 10 microM of the AMP precursor adenylosuccinate weakly
      inhibited the channel activity. An increase in AMP concentration from 1 to 10
      microM shifted the EC(50) for Ca(2+) activation almost 1 order of magnitude; a
      Schild plot analysis yielded a K(B) value of 0.3 microM for AMP. We conclude that
      AMP is the most efficacious endogenous nucleotide inhibitor of the brown
      adipocyte nonselective cation channel (NSC(Ca/AMP)) yet identified and that there
      is functional competition between Ca(2+) and AMP. The brown adipocyte NSC(Ca/AMP)
      thus appears to be functionally different from the NSC(Ca,PKA) in the exocrine
      pancreas and the NSC-(Ca,cAMP) in the endocrine pancreas, but similar to the
      NSC(Ca/AMP) in the endocrine pancreas.

PMID- 12181609
TI  - Genistein modifies the activation kinetics and magnitude of phosphorylated wild
      type and G551D-CFTR chloride currents.
AB  - We have studied the mechanism by which genistein activates cystic fibrosis
      transmembrane conductance regulator (CFTR) in CHO cells expressing wild type or
      G551D-CFTR. In wild-type CHO cells, after exposure to 2.5 microM forskolin, 25
      microM genistein induced a further 2-fold and rapid increase of the forskolin
      activated CFTR current. In both types of cells, when forskolin was added after
      genistein preincubation, whole-cell current density was greatly reduced compared
      to that measured when genistein was added after phosphorylation of CFTR, and all
      activation kinetic parameters were significantly altered. Genistein had no effect
      on the adenylate cyclase activity. Our results suggest that the occupancy of a
      putative genistein binding site is critical for the gating mechanism of CFTR
      chloride channels, which, depending on the phosphorylation status of the R
      domain, drives CFTR either into a refractory state or alternatively to a highly
      activated state.

PMID- 12181611
TI  - Wavelet analysis of nonequilibrium ionic currents in human heart sodium channel
      (hH1a).
AB  - Nonequilibrium response spectroscopy (NRS), the technique of using rapidly
      fluctuating voltage pulses in the study of ion channels, is applied here. NRS is
      known to drive an ensemble of ion channels far from equilibrium where, it has
      been argued, new details of ion channel kinetics can be studied under
      nonequilibrium conditions. In this paper, a single-pulse NRS technique with
      custom-designed waveforms built from wavelets is used. The pulses are designed to
      produce different responses from two competing models of a human heart isoform of
      the sodium channel (hH1a). Experimental data using this new type of pulses are
      obtained through whole-cell recordings from mammalian cells (HEK 293). Wavelet
      analysis of the model response and the experimental data is introduced to show
      how these NRS pulses can aid in distinguishing the better of the two models and
      thus introduces another important application of this new technique.

PMID- 12181612
TI  - Blue light modulation of ion transport in the slime mutant of Neurospora crassa.
AB  - Blue light is the primary entrainment signal for a number of developmental and
      morphological processes in the lower eucaryote Neurospora crassa. Blue light
      regulates photoactivation of carotenoid synthesis, conidiation, phototropism of
      perithecia and circadian rhythms. Changes in the electrical properties of the
      plasma membrane are one of the fastest responses to blue light irradiation. To
      enable patch-clamp studies on light-induced ion channel activity, the wall-less
      slime mutant was used. Patch-clamp experiments were complemented by non-invasive
      ion-selective measurements of light-induced ion fluxes of slime cells using the
      vibrating probe technique. Blue light usually caused a decrease in conductance
      within 2-5 minutes at both negative and positive voltages, and a negative shift
      in the reversal potential in whole-cell patch-clamp measurements. Both K+ and Cl-
      channels contribute to the inward and outward currents, based on the effects of
      TEA (10 mM) and DIDS (500 microM). However, the negative shift in the reversal
      potential indicates that under blue light the Cl- conductance becomes dominant in
      the electrical properties of the slime cells due to a decrease of K+ conductance.
      The ion-selective probe revealed that blue light induced the following changes in
      the net ion fluxes within 5 minutes: 1) decrease in H+ influx; 2) increase in K+
      efflux; and 3) increase in Cl- influx. Ca2+ flux was unchanged. Therefore, blue
      light regulates an ensemble of transport processes: H+, Cl-, and K+ transport.

PMID- 12181613
TI  - Functional studies on a split type II Na/P(i)-cotransporter.
AB  - Analysis of rat and mouse proximal tubular brush-border membrane expression of
      the type IIa Na/P(i)-cotransporter provides evidence for its cleavage in the
      large extracellular loop (ECL-2). To study functional properties and membrane
      distribution of this split NaP(i)-IIa transporter we followed two strategies. In
      one strategy we expressed the transporter as two complementary parts (p40 and
      p45) in Xenopus laevis oocytes and as another strategy we cleaved the WT protein
      with trypsin. Both strategies resulted in a split NaP(i)-IIa protein located in
      the plasma membrane. The two domains were tied together by a disulfide bridge,
      most likely involving the cysteines 306 and 334. Surface expression of the NaP(i)
      IIa fragments was dependent on the presence of both domains. If both domains were
      coexpressed, the transporter was functional and transport characteristics were
      identical to those of the WT-NaP(i)-IIa protein. Corresponding to this, the
      transporter cleaved by trypsin also retains its transport capacity. These data
      indicate that cleavage of the type IIa Na/P(i)-cotransporter at ECL-2 is
      compatible with its cotransport function.

PMID- 12181614
TI  - The phytotoxic lipodepsipeptide syringopeptin 25A from Pseudomonas syringae pv
      syringae forms ion channels in sugar beet vacuoles.
AB  - Syringopeptin 25A (SP(25)A) belongs to a family of cyclic lipodepsipeptides
      (LDPs) produced by the gram-negative bacterium Pseudomonas syringae, a
      phytopathogenic organism that affects several plants of agronomic interest. LDPs
      increase the permeability of plasma and, possibly, intracellular membranes in
      plant cells. Consistently, SP(25)A forms ion channels in planar lipid bilayers
      and other model membranes. Here we used sugar beet tonoplasts as a new biological
      model system to study toxin action. When applied to the vacuoles by a fast
      perfusion procedure, SP(25)A increases membrane permeability by forming discrete
      ion channels even at low applied potentials. The SP(25)A channel displays anion
      selectivity (with a Cl-/K+ permeability ratio of 6.7 +/- 1.3) and has intrinsic
      rectification properties that derive from a different channel conductance at
      negative and positive voltages, presumably owing to an asymmetric distribution of
      fixed charges on the pore. Substitution of chloride with different anions reveals
      the following selectivity sequence NO3- approximately Cl-> F- > gluconate-,
      suggesting that the permeation pore is filled with water. The properties of the
      SP(25)A channels in vacuolar membranes are similar to those observed in planar
      lipid membranes prepared with asolectin. This work provides a direct
      demonstration of toxin effects on a native plant membrane, extending to a
      biological system previous results obtained on artificial planar lipid membranes.

PMID- 12181615
TI  - Extracellular adenine nucleotides regulate Na+/H+ exchanger NHE3 activity in A6
      NHE3 transfectants by a cAMP/PKA-dependent mechanism.
AB  - As potential autocrine or paracrine factors, extracellular nucleotides are known
      to be important regulators of renal ion transporters by activating cell surface
      receptors and intracellular signaling pathways. We investigated the influence of
      extracellular adenine nucleotides on Na+/H+ exchanger isoform 3 (NHE3) activity
      in A6-NHE3 cells. This is a polarized cell line obtained by stable transfection
      of A6 cells with the cDNA encoding the rat isoform of NHE3, which is expressed on
      the apical membrane. Basolateral addition of the P2Y(1) agonist, 2-MeSADP,
      induced an inhibition of NHE3 activity, which was prevented by preincubation with
      selective P2Y(1) antagonists, MRS 2179 (N6-methyl-2'-deoxyadenosine-3',5'
      bisphosphate) and MRS 2286 (2-[2-(2-chloro-6-methylamino-purin-9-yl)-ethyl]
      propane-1,3-bisoxy(diammoniumphosphate)). NHE3 activity was also significantly
      inhibited by ATP and ATP-gamma-S but not by UTP. 2-MeSADP induced a P2Y(1)
      antagonist-sensitive increase in both [Ca2+]i and cAMP production. Pre-incubation
      with a PKC inhibitor, Calphostin C, or the calcium chelator BAPTA-AM, had no
      effect on the 2-MeSADP-dependent inhibition of NHE3 activity, whereas this
      inhibition was reversed by either incubation with the PKA inhibitor H89 or by
      mutation of two PKA target serines (S552 and S605) on NHE3. Pre-incubation of the
      A6-NHE3 cells with the synthetic peptide, Ht31, which prevents the binding
      between AKAPs and the regulatory PKA subunits RII, also prevented the 2-MeSADP
      induced inhibition of NHE3. We conclude that only the cAMP/PKA pathway is
      involved in the inhibition of NHE3 activity.

PMID- 12181616
TI  - Pharmacologic doses of medroxyprogesterone may cause bone loss through
      glucocorticoid activity: an hypothesis.
AB  - A number of studies suggest that progestagens may have beneficial effects on bone
      metabolism. C(21) Progestin medroxyprogesterone acetate (MPA) is one of the most
      commonly prescribed progestins for hormone replacement therapy and in gynecologic
      practice. However, it appears that MPA with significant glucocorticoid (GC)
      activity may decrease bone density. In this review, we argue that bone loss
      associated with MPA administration is caused by decreased osteoblast
      differentiation as a result of MPA occupying the GC receptor, since increasing GC
      receptor occupancy beyond that reached at normal (= optimal) GC concentrations
      attenuates osteoblast differentiation. We propose that progestins with no GC
      activity may be a better choice for progestagen therapy to achieve more
      beneficial effects on bone metabolism.

PMID- 12181618
TI  - Does osteoporosis classification using heel BMD agree across manufacturers?
AB  - The lack of standardization in bone mineral density (BMD) measurements is known.
      Several studies have been carried out to cross-calibrate the axial dual X-ray
      absorptiometry (DXA) devices. Recently, a number of peripheral DXA (pDXA)
      densitometers have been introduced. In this study we evaluated the agreement
      between two heel DXA devices on BMD and T-scores. A total of 99 females aged 21
      78 years (ca. 16 per decade) had their non-dominant heel BMD measured using the
      PIXI (Lunar Inc.) and the Apollo (Norland Medical) pDXA scanners. The mean BMD
      values were 0.492 and 0.607 g/cm(2) and the mean T-scores using manufacturers'
      specified reference data were -0.07 and -0.25 for the PIXI and Apollo,
      respectively. Both the BMD and T-score intermachine relationships were highly
      correlated but showed significant nonidentity slopes and non-zero offsets. The
      diagnostic comparison on T-scores resulted in 86% agreement between the
      instruments (weighted kappa score of 0.550). Normalizing the reference peaks and
      SDs using this study's young adult population BMD results removed the systematic
      T-score disagreement. We found that PIXI and Apollo are highly correlated.
      Differences in BMD values are mainly due to different region of interest (ROI)
      definitions and additional T-score disagreement reflects the difference in
      normative databases.

PMID- 12181617
TI  - Quantitative ultrasound and mortality: a prospective study.
AB  - Previous studies suggest that low bone mineral density (BMD) is associated with
      increased mortality, but the relationship between quantitative ultrasound (QUS)
      and mortality is unknown. We studied 5816 women over age 70 years enrolled in the
      Study of Osteoporotic Fractures. QUS of the calcaneus, and BMD of the calcaneus
      and hip, were measured at baseline, and women were contacted every 4 months to
      determine vital status. All reported deaths were confirmed by review of the death
      certificate or hospital records, and classified by ICD-9 code. During 5.0 years
      of follow-up, 677 women died. Women in the lowest quintile of QUS had the highest
      mortality during follow-up. After adjustment for age, grip strength, weight,
      height, health status, estrogen use, smoking, physical activity, and history of
      hypertension, diabetes, cardiovascular disease, cancer and stroke, each 1 SD
      reduction in broadband ultrasonic attenuation (BUA) was associated with a 16%
      increase in mortality (RH = 1.16; 95% CI: 1.07, 1.26). Mortality from
      cardiovascular disease, cancer and other causes were all increased among women
      with low QUS, but the association with cancer deaths was not statistically
      significant after multiple adjustments (RH = 1.09; CI: 0.93, 1.27). Low BMD was
      also associated with an increased risk of total and cause-specific mortality, but
      we found little evidence that BUA and BMD were independent predictors of
      mortality. Results were similar among women who did not fracture during follow
      up. In this large population-based study of older women, low QUS is associated
      with both total and cause-specific mortality. This relationship was independent
      of other factors associated with mortality, such as age and health status, and
      suggests QUS and BMD may reflect some aspect of aging not captured by these
      traditional factors.

PMID- 12181619
TI  - Uneven deficits in vertebral bone density in postmenopausal patients with primary
      hyperparathyroidism as evaluated by posterior-anterior and lateral dual-energy
      absorptiometry.
AB  - This investigation was undertaken to determine whether the preservation of bone
      mass in patients with mild primary hyperparathyroidism (PHPT) could be detected
      when measuring spine density in the lateral projection. We compared the bone
      mineral density (BMD) of L2-L4 utilizing the posterior-anterior (PA) and lateral
      projections in postmenopausal patients with PHPT and in a group of 27
      postmenopausal normal women. Thirty-three consecutive postmenopausal patients
      with PHPT were studied; 25 were asymptomatic whereas the remaining 8 suffered
      complications related to the disease. Based upon the criteria established by the
      Consensus Conference on the Management of Asymptomatic PHPT, only 10 of the 25
      asymptomatic patients could be considered affected by mild disease; the remaining
      patients were classified as having moderate disease. Patients with mild disease
      had mean lateral total BMD values (0.682 +/- 0.113 g/cm(2)) significantly higher
      than normal women (0.588 +/- 0.076, p<0.02) and patients with moderate disease
      (0.599 +/- 0.077, p<0.05). There were significant differences among the three
      groups in both PA L2-L4 and L1-L4 levels: patients with mild disease had
      significantly higher mean BMD values than patients with moderate disease and
      normal women, when either three or four vertebrae were considered. Interestingly,
      at this latter site, patients with moderate disease had significantly ( p<0.05)
      lower values than normal women. Our results indicate that patients with mild PHPT
      have a preservation of vertebral mass when compared with the other
      hyperparathyroid patients and normal women, when taking into account both the
      mainly trabecular portion and the whole vertebra. The finding that when the PA
      projection was assessed, BMD values of patients with moderate disease were
      significantly lower than those of normal women, might be attributed to the
      detrimental effect of raised parathyroid hormone levels on the cortical component
      of the vertebral body.

PMID- 12181620
TI  - Does a fracture at one site predict later fractures at other sites? A British
      cohort study.
AB  - The extent to which a fracture at one skeletal site predicts further fractures at
      other sites remains uncertain. We addressed this issue using information from the
      UK General Practice Research Database, which contains the medical records of
      general practitioners; our study population consisted of all patients aged 20
      years or older with an incident fracture during 1988 to 1998. We identified 222
      369 subjects (119 317 women, 103 052 men) who had sustained at least one fracture
      during follow-up. There was a 2- to 3-fold increase in the risk of subsequent
      fractures at different skeletal sites. A patient with a radius/ulna fracture had
      a standardized incidence ratio (SIR) of 3.0 (95% confidence interval 2.9-3.1) for
      fractures at a different skeletal site; for initial vertebral fracture, this
      ratio was 2.9 (2.8-3.1) and for initial femur/hip fracture it was 2.6 (2.5-2.7).
      The SIRs were generally higher among men than women. Men aged 65-74 years with a
      radius/ulna fracture or vertebral fracture had substantially higher rates of
      subsequent femur/hip fractures than expected; SIRs were 6.0 (3.4-9.9) and 13.4
      (7.3-22.5). Corresponding SIRs among women of similar age were 3.3 (2.8-3.9) and
      5.8 (4.1-8.1), respectively. Men and women aged 65 years or older with a
      vertebral fracture had a 5-year risk of femur/hip fracture of 6.7% and 13.3%,
      respectively. Our results indicate that fractures at any site are strong risk
      factors for subsequent fractures, among both elderly men and women.

PMID- 12181621
TI  - Is distal forearm fracture in men due to osteoporosis?
AB  - Although widely regarded as a disease of women, osteoporosis does cause
      considerable morbidity and mortality in men. The lifetime risk of an
      osteoporortic fracture for a man is 1 in 12 and 30% of all hip fractures occur in
      men. In women, low-trauma distal forearm fracture is widely regarded as a typical
      early manifestation of postmenopausal osteoporosis. Traditionally, this has not
      been thought to be the case for men. We present a case-control study of 147 men
      with distal forearm fracture compared with 198 age-matched controls. The controls
      were selected from a pre-existing database of dual-energy X-ray absorptiometry
      scans of healthy volunteers. Both groups were sent questionnaires regarding basic
      demographics, fracture history and risk factors for osteoporosis, and the
      fracture group was asked to attend for bone densitometry. There were 103
      responses from the fracture group (70%), of whom 67 (47%) underwent densitometry.
      There were 165 (83%) responses from the control group. Secondary causes of
      osteoporosis could be identified in 51% of the fracture group and 37% of the
      control group. The fracture group had significantly lower bone mineral density at
      all sites measured compared with the controls (0.75 g/cm(2) vs 0.85 g/cm(2) at
      the femoral neck, p<0.0001; 0.95 g/cm(2) vs 1.03 g/cm(2) at the total femur, p =
      0.001; and 0.99 g/cm(2) vs 1.06 g/cm(2) at the lumbar spine, p = 0.001). These
      differences remained after adjusting for age and body mass index ( p<0.0005 at
      all sites). Overall, 41.8% of the fracture group were osteoporotic in at least
      one site ( T-score <-2.5 SD below the mean for young men) compared with only
      10.3% of controls. This study is the first to demonstrate that men with distal
      forearm fractures have lower bone mineral density than their peers and a higher
      risk of osteoporosis.

PMID- 12181622
TI  - Cost-effectiveness of hormone replacement therapy for fracture prevention in
      young postmenopausal women: an economic analysis based on a prospective cohort
      study.
AB  - A recent systematic review of randomized controlled trials has shown that hormone
      replacement therapy (HRT) prevents fractures when taken soon after the menopause.
      HRT for treatment of menopausal symptoms is relatively cost-effective, but
      whether its use for prevention of perimenopausal fractures is economically
      efficient is unknown. We undertook a 6-year follow-up of 3645 perimenopausal
      women who had a bone mineral density (BMD) measurement with recommendation to use
      HRT if low BMD was present. Data were collected on incident fractures and costs.
      After an average of 6.2 years of follow-up HRT use significantly reduced incident
      fractures by 52% (95% CI: 67% to 18%). However, costs were increased by an
      average of pounds sterling 275 (95% CI: pounds sterling 228 to pounds sterling
      330) for the group as a whole; for hysterectomized women costs were increased
      less (pounds sterling 138), but this was still significantly greater than for non
      HRT users (95% CI: pounds sterling 6 to pounds sterling 275). The cost per
      averted fracture was about pounds sterling 11 000 (95% CI: pounds sterling 8625
      to pounds sterling 13 872) for the whole group and for hysterectomized women the
      corresponding figure was substantially less (pounds sterling 1784; 95% CI: pounds
      sterling 59 to pounds sterling 3532). HRT given to women at or shortly after the
      menopause is therefore associated with a halving of fracture incidence. Such a
      policy for hysterectomized women without menopausal symptoms may be cost
      effective as such women are at elevated risk of fracture and need cheaper,
      unopposed, estrogens.

PMID- 12181623
TI  - Bisphosphonates in the treatment of thalassemia-induced osteoporosis.
AB  - The aim of our randomized, placebo-controlled study was to investigate the
      effects of 2 years' daily oral administration of alendronate or intramuscular
      administration of clodronate every 10 days, on bone remodeling parameters and
      bone mineral density (BMD), safety and tolerability in a group of osteoporotic
      thalassemic patients. Twenty-five young patients (mean age 26.6 +/- 7.1 years)
      with beta-thalassemia major were randomly divided to receive placebo or 100 mg of
      clodronate intramuscularly every 10 days or 10 mg of alendronate per os daily.
      All patients took 500 mg of elemental calcium and 400 IU cholecalciferol in the
      evening at meal time. After 2 years, pyridinium crosslinks, which are bone
      resorption markers, did not differ significantly from baseline values in the
      placebo group, whereas they had decreased significantly in the clodronate and
      alendronate groups. Osteocalcin, a bone formation marker, did not change
      significantly in the placebo group, whereas it decreased slightly, but not
      significantly, in the clodronate and alendronate groups after 12 and 24 months.
      At the end of the study, the lumbar spine BMD had decreased significantly in the
      placebo group; it did not change significantly in the clodronate group; in the
      alendronate group it had increased but not significantly, whereas the increase
      was significant with respect to the placebo group. Femoral neck BMD decreased
      significantly in the placebo group; it did not change significantly in the
      clodronate group, but increased significantly in the alendronate group. No
      relevant side effects were recorded during our study. In conclusion, in patients
      with thalassemia-induced osteoporosis, the daily administration of alendronate
      significantly increases BMD, the most important predictor of the risk of fracture
      at several sites. Clodronate treatment at our dosage is ineffective in this
      pathology in spite of the good compliance of patients.

PMID- 12181624
TI  - Vertebral fracture and cortical bone changes in corticosteroid-induced
      osteoporosis.
AB  - Despite an intriguing understanding of trabecular bone dynamics, little is known
      about corticosteroid-induced cortical bone loss and fractures. Recently, we
      verified a steroid-induced decrease in cortical bone volume and density using
      peripheral quantitative computed tomography (pQCT) in adult asthmatic patients
      given oral corticosteroids. Subsequently, the pQCT parameters and presence of
      vertebral fractures were investigated to further clarify the role of cortical
      bone quality in fractures in 86 postmenopausal (>5 years after menopause)
      asthmatic patients on high-dose oral steroid (>10 g cumulative oral prednisolone)
      (steroid group) and 194 age-matched controls (control group). Cortical and
      trabecular bone was subjected to measurement of various parameters using pQCT
      (Stratec XCT960). Relative Cortical Volume (RCV) was calculated by dividing the
      cortical area by the total bone area. Strength Strain Index (SSI) was determined
      in the radius based on the density distribution around the axis. Spinal fracture
      was assessed on lateral radiographs. Patients treated with high doses of oral
      steroid (>10 g cumulative oral prednisolone) were found to have an increased risk
      of fracture compared with control women receiving no steroid medication (odds
      ratio, 8.85; 95% CI, 4.21-18.60) after adjustment was made for years since
      menopause, body mass index and RCV. In both groups, the diagnostic and predictive
      ability of the pQCT parameters for vertebral fracture was assessed by the areas
      under their receiver operating characteristic (ROC) curves. All parameters were
      found to be significant predictors ( p<0.0001) in the control group. In the
      steroid group, however, the cortical bone mineral density (BMD) ( p = 0.001), RCV
      ( p<0.0001) and SSI ( p = 0.001) were found to be significant predictors, but not
      trabecular BMD ( p = 0.176). For comparison between the two groups, thresholds of
      all parameters for vertebral fracture were also calculated by the point of
      coincidence of sensitivity with specificity in ROC testing and the 90th
      percentile value. Although a rise in fracture threshold in the steroid group was
      suggested, considerable difference in the values obtained by the two methods of
      calculation precluded any conclusion. High-dose oral steroid administration was
      associated with an increased risk of fracture. Cortical bone parameters obtained
      by pQCT could play a role as good predictors of future corticosteroid-induced
      vertebral fractures.

PMID- 12181625
TI  - Calcium supplement and bone medication use in a US Medicare health maintenance
      organization.
AB  - This study was conducted to determine the prevalence of the use of calcium
      supplements and of prescription medications to prevent or treat osteoporosis in
      men and women in a large New England Medicare Health Maintenance Organization
      (HMO). A two-page diet, medication use and medical history questionnaire was sent
      to a random sample of 9000 out of 82 985 members and 2932 (32.6%) responded. Over
      97% of the participants were Caucasian and 64.7% were female. The mean ages of
      the men and women were 74.4+/-5.8 and 74.6+/-6.2 years, respectively. Sixty-nine
      percent of the men and 59% of the women consumed two or fewer servings of dairy
      foods per day. Calcium supplement use was more prevalent among the women than the
      men (66.8% vs 24.9%, p<0.001). Men and women with higher dairy food intakes were
      more likely to take calcium supplements than were those with lower dairy intakes.
      Prescription bone medications (including bisphosphonates, raloxifene and
      calcitonin) were used currently by 17.5% of the women and 2.3% of the men (
      p<0.001). An additional 16.2% of the women currently took estrogen. Among the
      women, bone medication use did not change with age but estrogen use declined with
      increasing age. Among women age 80+ years, 15.6% used bone medications and 4.9%
      took estrogen. According to a national survey, more than half the US Caucasian
      female population over age 80 years has bone density low enough to warrant
      treatment under current guidelines. Based on the results of this survey, many
      elderly men and women may benefit from increased utilization of calcium
      supplements and bone-active medications.

PMID- 12181626
TI  - Household tobacco smoke exposure is negatively associated with premenopausal bone
      mass.
AB  - Subjects exposed to environmental tobacco smoke have been found to be at
      increased risk for several health problems. Whether exposure to passive tobacco
      smoke is associated with reduced bone mineral density (BMD) is unknown. In order
      to examine this, we measured BMD in 154 healthy premenopausal women (age range 40
      45 years). BMD of the total hip, femoral neck, lumbar spine and total body was
      measured by dual-energy X-ray absorptiometry (DXA). Data were collected on
      exposure to household tobacco smoke from age 10 years to the present as well as
      on other lifestyle factors related to bone mass. We found that 67.5% of the
      subjects had a history of household tobacco smoke exposure. Subjects exposed to
      household tobacco smoke had a mean adjusted BMD that was significantly lower at
      the total hip ( p = 0.021) and femoral neck ( p = 0.018) compared with subjects
      who were not exposed. In addition, duration of household tobacco smoke exposure
      was negatively associated with BMD at the total hip ( p = 0.010), femoral neck (
      p = 0.004), lumbar spine ( p = 0.037) and total body ( p = 0.031). Subjects
      exposed to household tobacco smoke for 15 years or more had mean adjusted BMD
      that was 4% lower at the total body, and more than 8% lower at the total hip,
      femoral neck and lumbar spine, compared with subjects who were not exposed. In
      conclusion, household tobacco smoke exposure during adolescence and young
      adulthood was found to be negatively associated with BMD at the total hip and
      femoral neck, and duration of exposure was negatively associated with BMD at the
      total hip, femoral neck, lumbar spine and total body in premenopausal women.

PMID- 12181627
TI  - Age-related bone mineral density, accumulated bone loss rate and prevalence of
      osteoporosis at multiple skeletal sites in chinese women.
AB  - We investigated the age-related bone mineral density (BMD), accumulated bone loss
      rate (ABLR) and the prevalence of osteoporosis at different skeletal sites in
      Chinese women. BMD was measured at the anteroposterior (AP) spine, supine lateral
      spine (areal BMD at the midarea [mLat] and the whole region [Lat], volumetric BMD
      at the middle region [MVD] and total region [TVD]), hip (femoral neck [FN],
      trochanter [Troc] and Ward's triangle [Ward's]) and forearm (radius + ulna
      ultradistal [RUUD], 1/3 region [RU1/3] and total region [RUT]) using a dual
      energy X-ray absorptiometry (DXA) fan-beam bone densitometer (Hologic QDR 4500A)
      in 2702 females aged from 5 to 96 years old. Data were analyzed by eight
      different regression models. We found that the cubic regression model was the
      best for describing age-related changes in BMD. The coefficients of determination
      ( R(2)) of the fitting curve were 0.398 to 0.612 ( p = 0.000). The data were then
      analyzed by 5-year age groups. This showed that the earliest peak BMD was at the
      age of 20-24 years at Troc and Ward's, and the latest at the age of 40-44 years
      at RU1/3 and RUT of the distal forearm. Compared with BMD, the ABLRs were highest
      at Ward's (-66.2%) and the lowest at RU1/3 of the distal forearm (-31.3%) in
      subjects over 80 years old. The prevalence of osteoporosis at at least one site
      in these women was 0.5 +/- 0.4% in those 30-39, 4.6 +/- 4.4% in those 40-49, 23.9
      +/- 13.3% in those 50-59, 56.3 +/- 20.3% in those 60-69, 71.8 +/- 16.7% in those
      70-79 and 83.2 +/- 12.1% those over 80 years of age, respectively. The prevalence
      of osteoporosis in these women was 8.6-11.1% at the age of 40-49 and 36.5-40.6%
      at the age of 50-59 at the lateral spine regions (mLat, Lat, MVD and TVD), and
      0.5-3.7% at the age of 40-49 and and 3.9-21.7% at the age of 50-59 years at the
      other skeletal sites (AP, FN, Troc, Ward's, RUUD, RU1/3 and RUT). Significant
      differences were found in the prevalence of osteoporosis between the lateral
      spine regions and other skeletal sites ( p<0.001) at the age of 40-59 years. In
      summary, we demonstrated significant age-related differences in peak BMD, ABLR
      and osteoporosis prevalence among various skeletal sites. Our data suggest that
      the supine lateral spine is the most sensitive site for the diagnosis of
      osteoporosis, especially in the early menopausal period, although the prevalence
      of osteoporosis varied with age and with different sites measured.

PMID- 12181628
TI  - Ursodeoxycholic acid enhances fractional calcium absorption in primary biliary
      cirrhosis.
AB  - Bone disease is a frequently reported complication in primary biliary cirrhosis
      (PBC), but its pathogenesis is poorly understood. Calcium malabsorption has been
      considered as an important contributing factor. Ursodeoxycholic acid (UDCA) is
      the treatment of choice in PBC, improving survival, but its effect on calcium
      absorption is unknown. In this study, we have measured fractional calcium
      absorption, using a single isotope method, in a group of female PBC patients
      (median age: 60 years, range: 46-78 years) and age-matched female controls
      (median age: 58 years, range: 36-74). Bone mineral density (BMD) in PBC patients
      was significantly lower than age-matched controls (g/cm(2) +/- SEM; lumbar spine:
      controls 1.139+/-0.028, PBC patients 1.004+/-0.026, p = 0.0028; femoral neck:
      controls 0.944+/-0.034, PBC patients 0.819+/-0.023, p = 0.0032). Twenty two PBC
      patients, who were not vitamin D-deficient, were off and on UDCA for
      approximately 1 month and approximately 8 weeks, respectively. Fractional calcium
      absorption in PBC patients prior to UDCA treatment (mean +/- SEM, 33.8+/-2.6%)
      was significantly lower than controls (52.0+/-2.4%, p<0.001). Following UDCA
      therapy, fractional calcium absorption increased significantly (Off UDCA: 33.1+/
      2.6%, On UDCA: 36.6+/-2.5%, p<0.0058). Osteocalcin levels were significantly
      raised in the PBC group (mean +/- SEM, ng/ml, 41.4+/-2.02) compared to controls
      (31.1+/-2.64, p = 0.002). There were no differences in parathyroid hormone (PTH)
      or 25-hydroxyvitamin D levels between these two groups or following UDCA therapy.
      In conclusion, we found that PBC patients display low spinal and femoral neck
      BMD, reduced fractional calcium absorption, and elevated plasma osteocalcin. The
      calcium malabsorption is corrected partially by UDCA therapy. Long-term studies
      are required to determine whether this effect can be sustained, and whether a
      sustained increase in fractional calcium absorption can translate into a
      favorable change in bone strength in patients with PBC.

PMID- 12181629
TI  - Effects of diode laser therapy on blood flow in axial pattern flaps in the rat
      model.
AB  - Axial pattern skin flaps are a very important reparative tool for the plastic and
      reconstructive surgeon in the reconstruction of tissue defects. From whatever
      unfortunate reason, part or all of such flaps occasionally suffers from
      irreversible ischaemia with loss of the flap. Infrared diode laser therapy has
      been shown to improve local and systemic circulation. The present study was
      designed to assess the effect of an 830 nm diode laser (power density, 18.5
      W/cm(2), energy density 185 J/cm(2)) on the blood flow of axial pattern flaps in
      the rat model and their survival, compared with unirradiated controls. The flaps
      were raised in all animals ( n=40), and blood flow assessed with laser speckle
      flowmetry (LSF). In the experimental groups (3 groups, n=10 per group), the flaps
      were irradiated either directly over the dominant feeder vessel (iliolumbar
      artery), at the proximal end or at the distal end of the flap itself and blood
      flow assessed during irradiation. Flowmetry was performed again in all animals at
      5 and 10 min postirradiation, and the flaps sutured back in position. The
      unirradiated controls were handled in exactly the same way, but the laser was not
      activated. The survival rate of the flaps was assessed on the fifth postoperative
      day. LSF demonstrated significant increased blood flow in the flaps at 5 and 10
      min postirradiation in all experimental groups compared with the control animals.
      At five days postirradiation, there was significantly better survival of the
      flaps in all the experimental groups compared with the controls ( p<0.01), but no
      significant difference was seen between any of the experimental groups. We
      conclude that laser therapy increases the blood flow and perfusion of transferred
      flaps, and that this has significant effects on the survival of the flaps. One
      possible mechanism of modulation of the autonomic nervous system is discussed.

PMID- 12181630
TI  - In vivo study of intradermal focusing for tattoo removal.
AB  - Delivery of intradermally focused nanosecond laser pulses with small energy as an
      alternate technique applicable to clinical procedures in dermatological and
      plastic surgery is an area of relatively new interest with multiple potential
      applications. We assessed this approach on common tattoo pigments in dermis in an
      in vivo study using a wavelength of 1064 nm. Paired micropigs were tattooed with
      standard blue, black, green and red pigments. The tattoos were allowed to mature
      and then treated by 12 ns pulses in a focused beam of 11.4 degrees cone angle.
      Visual observation and histological analysis of biopsies were performed to
      evaluate results. Significant reduction in pulse energy and collateral damage was
      achieved with pulse energy ranging between 38 to 63 mJ. Blue and black tattoos
      were found to respond well from a clinical standpoint. The depth dependence of
      tissue response and pigment redistributions at 1 hour, 1 week and 1 month after
      laser treatment was quantitatively analysed through biopsies and a strong
      relationship was demonstrated between tattoo response and laser-induced dermal
      vacuolation. The optical absorption coefficients of the four tattoo pigments were
      measured to be approximately the same and the laser-induced plasma is suggested
      to be responsible for the pigment redistribution. As we hypothesised, intradermal
      focusing of nanosecond pulses significantly reduced required pulse energy for
      tattoo ablation to about 60 mJ or less. These results stimulate a number of
      additional questions relevant not only to clinical applications but also to the
      understanding of the fundamental process of laser-pigment interaction in the
      dermis as it relates to tattoo removal.

PMID- 12181631
TI  - A novel method of drug delivery for fibrinolysis with Ho:YAG laser-induced liquid
      jet.
AB  - Two of the problems inherent in the treatment of cerebral emboli are the narrow
      therapeutic time window and the severe side effects of fibrinolytic drugs. Thus,
      it is necessary to develop a new method of removing a cerebral thrombus more
      rapidly and with smaller quantities of fibrinolytics. The behaviour of a bubble
      formed by holmium (Ho):YAG laser irradiation in a capillary tube filled with pure
      water was observed at various stand-off distances (L; distance between the end of
      optical fibre and the capillary exit). Subsequently, a liquid-jet generator was
      created by insertion of an optical fibre (core diameter: 0.6 mm) into a catheter
      (6 Fr) filled with pure water, and a pulsed Ho:YAG laser (pulse duration time=350
      micros, laser energy=230 mJ/pulse) was used to irradiate the optical fibre. The
      maximum penetration depth, into a gelatin artificial thrombus, of a liquid jet
      generated with this device was measured for various stand-off distances.
      Additionally, the phenomenon and the pressure around the catheter exit were
      captured via shadowgraph and PVDF needle hydrophone, respectively. The laser
      induced bubble in the capillary tube grew rapidly in the direction of propagation
      and generated a liquid jet. The maximum penetration depth of this liquid jet into
      an artificial thrombus increased in proportion to L and reached a maximum value
      (9 mm) when L was around 13 mm. A shock wave whose overpressure at a point 4 mm
      away from the catheter exit exceeded 12 MPa was captured by shadowgraph. It was
      concluded that Ho:YAG laser irradiation within a water-filled catheter caused
      liquid jet formation, which could penetrate straight into an artificial thrombus.
      Hence, this jet is expected to promote fibrinolysis by means of injecting
      fibrinolytics deeply into the thrombus. After resolving some problems, this
      system will be applied to an endovascular therapy for cerebral embolisms in the
      near future.

PMID- 12181632
TI  - Laser and non-laser light sources for photodynamic therapy.
AB  - Photodynamic therapy (PDT) is an anticancer combination therapy, which requires a
      photosensitiser, which tends to accumulate preferentially in the tumour, and
      light. Historically large, complex lasers have been used to carry out PDT
      treatment. Nowadays there is a wide range of coherent and non-coherent sources
      that can be used. This paper considers the important characteristics of light
      sources for PDT, including dye lasers pumped by argon or metal vapour lasers and
      frequency-doubled Nd:YAG lasers. Non-laser sources including tungsten filament,
      xenon arc, metal halide and fluorescent lamps are also discussed. New exciting
      developments such as LEDs and femtosecond lasers are also reviewed. The relative
      merits of laser and non-laser sources are critically examined.

PMID- 12181633
TI  - Ultrastructural changes in thyroid perifollicular capillaries during normal
      postnatal development and after infrared laser radiation.
AB  - This study was carried out on the perifollicular capillaries of the thyroid gland
      during postnatal (PN) development in normal conditions and after irradiation
      (46.8 J/cm(2)) with an infrared (IR) laser (904 nm). This was done using 11-, 21
      , and 35-day-old Wistar rats. The changes in the capillaries were determined
      using quantitative methods as well as electron microscopy. During normal PN
      development the most relevant changes were an increase in the size of the
      capillaries, especially the lumen, thinning of the endothelium and an increase in
      the size of pinocytotic vesicles. Our results suggest that during PN development,
      the capillaries undergo some growth and maturation processes until they reach the
      optimal morphological conditions for their exchange functions. IR laser
      irradiation seems to stimulate the growth and maturation of endothelial cells in
      the youngest rats, while in older ones it causes irregular thickening of the
      endothelium and a reduction of the capillary lumen. These changes could be a sign
      of functional alterations in follicular cells caused by exposure to IR laser.

PMID- 12181634
TI  - Er:YAG laser modification of root canal dentine: influence of pulse duration,
      repetitive irradiation and water spray.
AB  - The aim of this study was to determine the effects of varying parameters of
      Er:YAG laser irradiation with and without water spray cooling on root canal
      dentine in vitro. After horizontally removing tooth crowns from extracted human
      teeth, roots were axially sectioned into thin slices, exposing the root canal
      surface. An Er:YAG laser delivered 10-30 J/cm(2) into a 0.4-mm diameter laser
      spot on the root canal surface. Single pulses of different lengths (80-280 micro
      s) were applied with and without water spray cooling/irrigation, and sequences of
      three pulses at a repetition rate of 30 Hz were applied at selected pulse
      parameters. The irradiated samples were investigated using both confocal laser
      scanning microscopy (CLSM) and scanning electron microscopy (SEM). At most
      irradiation conditions, the root canal dentine surface was ablated. Three
      dimensional images from CLSM revealed that the cavity walls were not smooth.
      Depths of the cavities revealed significant differences between the cavities. No
      debris was observed at the surface of cavities at any irradiation condition.
      Strong melting and recrystallisation, or unusually flat surfaces with open
      dentinal tubules were obtained with sequences of three pulses without water
      cooling. CLSM is an effective tool for investigation of laser effects on root
      canal dentine. By varying the irradiation conditions, the Er:YAG laser can induce
      different modifications of root canal surface, which may be very interesting for
      root canal preparation.

PMID- 12181635
TI  - Development of a stable solution of 5-aminolaevulinic acid for intracutaneous
      injection in photodynamic therapy.
AB  - Photodynamic therapy using 5-aminolaevulinic acid (ALA) as a photosensitiser is a
      new treatment modality for basal cell carcinomas. Until now ALA has been used
      topically as a cream. As this administration route leads sometimes to
      insufficient penetration in the skin, an intracutaneously injectable solution of
      ALA was developed. The influence of pH, concentration and temperature on the
      degradation of ALA in aqueous solution was investigated in order to optimise the
      formulation of the injection. In 0.1% ALA solutions with pH values between 4 and
      8 a pH dependency of ALA degradation was shown, comprising fast decomposition at
      pH values higher than 7, whereas at a pH value of 6 or lower the solutions
      remained within the range of 90-110% of the initial concentration for at least
      128 days. An increase of degradation rate with increasing concentrations became
      evident which is consistent with the supposed second-order degradation kinetics.
      After accelerated stability research at 63 degrees C and 85 degrees C a shelf
      life of 281 days for a 0.1% ALA solution pH 5 was calculated from an Arrhenius
      plot. A 2% ALA solution was proven to be isotonic. From our results a 0.1-2% ALA
      solution with pH 5 and an appropriate amount of sodium chloride to obtain
      isotonicity is recommended as an injectable solution.

PMID- 12181636
TI  - Laser stimulation on bone defect healing: an in vitro study.
AB  - The aim of this in vitro study was to evaluate whether low-power laser (LPL)
      stimulation can accelerate bone healing. Bone defects of a standard area were
      created in the distal epiphysis of 12 femora explanted from six rats, and they
      were cultured in BGJb medium for 21 days. Six defects were treated daily with Ga
      Al-As, 780 nm LPL for 10 consecutive days (lased group, LG), while the remainder
      were sham-treated (control group, CG). Alkaline phosphatase/total protein
      (ALP/TP), calcium (Ca), and nitric oxide (NO) were tested on days 7, 14 and 21 to
      monitor the metabolism of cultured bone. The percentage of healing of the defect
      area was determined by histomorphometric analysis. After 21 days significant
      increases were observed in ALP/TP in LG versus CG (p<0.001), in NO in the LG
      versus CG ( p<0.0005) and in Ca in CG versus LG ( p<0.001). The healing rate of
      the defect area in the LG was higher than in the CG ( p=0.007). These in vitro
      results suggest that Ga-Al-As LPL treatment may play a positive role in bone
      defect healing.

PMID- 12181637
TI  - Is there anticipation in the age at onset of cancer in families with Li-Fraumeni
      syndrome?
AB  - Anticipation in the age at onset of cancer in successive generations was
      described in several familial cancer syndromes. Based on multiple statistical
      analyses of a database of families with germline TP53 mutations, and using
      several different approaches and measures to eliminate possible biases, we show
      that anticipation may be a feature of the Li-Fraumeni syndrome. Definitive proof
      of anticipation in pedigrees with germline TP53 mutations will require more
      family data and further analysis, as well as research on the role of the p53
      protein in processes like genome stability, which may represent the biological
      basis of anticipation in these families. This should have important practical
      implications for genetic testing, counselling, and preventative care for
      individuals at risk.

PMID- 12181638
TI  - Verification of 525 coding SNPs in 179 hypertension candidate genes in the
      Japanese population: identification of 159 SNPs in 93 genes.
AB  - Single-nucleotide polymorphisms (SNPs) located in coding regions (coding SNPs;
      cSNPs) with amino acid substitution can potentially alter protein function.
      Therefore, identification of the nonsynonymous cSNPs of the genes of common
      diseases is valuable in tests of association with phenotypes. In this study, we
      validated 525 candidate cSNPs from 179 hypertension candidate genes deposited in
      the publicly available database dbSNP by DNA sequencing of samples from 32
      Japanese individuals. We identified a total of 143 SNPs (27%) in 93 hypertension
      candidate genes. We also identified 16 new SNPs, for a total of 159 SNPs. Of the
      159 SNPs thus identified, 104 were nonsynonymous. We estimate that approximately
      20% of the SNPs deposited in dbSNP database showed a minor allele frequency of
      over 5%. The candidate SNPs for hypertension identified in this study would be
      valuable for association studies with hypertension to accelerate the
      identification of hypertension genes.

PMID- 12181639
TI  - Confirmation of genetic homogeneity of nonsyndromic low-frequency sensorineural
      hearing loss by linkage analysis and a DFNA6/14 mutation in a Japanese family.
AB  - Nonsyndromic low-frequency sensorineural hearing loss (LFSNHL) comprises a group
      (DFNA1, DFNA6, DFNA14, and DFNA38) of hearing disorders affecting only
      frequencies below 2000 Hz, and is often associated with tinnitus. An LFSNHL locus
      has recently been assigned to chromosome 4p16, and mutations in WFS1, the
      causative gene for Wolfram syndrome, have been found to cause LFSNHL in families
      with DFNA6, DFNA14, or DFNA38. We performed a genome-wide linkage analysis of a
      Japanese family in which 20 members were affected with LFSNHL and obtained a
      maximum LOD score of 5.36 at a recombination fraction of 0.05 ( P = 1.00) at the
      D4S2983 locus on 4p16. Haplotype analysis revealed that the disease locus mapped
      to between D4S2366 and D4S2983. Mutation analysis revealed a novel missense
      mutation (K634T) in WFS1. We thus concluded that the LFSNHL in this family was
      caused by the WFS1 mutation. The mutation observed (K634T) was located in the
      hydrophobic, extracytoplasmic, juxta-transmembrane region of the WFS1 protein,
      wolframin, and was hitherto undescribed. This unique mutation site in our
      patients is likely related to their milder phenotype (lacking tinnitus) compared
      with those of six previous DFNA6/14 patients with WFS1mutations. It is likely
      that a genotype-phenotype correlation is also applicable in the case of
      DFNA6/14/38.

PMID- 12181640
TI  - Linkage and association analyses of the osteoprotegerin gene locus with human
      osteoporosis.
AB  - Osteoprotegerin (OPG), a secreted glycoprotein and a member of the tumor necrosis
      factor receptor superfamily, is considered to play an important role in the
      regulation of bone resorption by modifying osteoclast differentiation.
      Overexpression of OPG in mice has been reported to result in osteopetrosis,
      whereas targeted disruption of OPG in mice has been associated with osteoporosis.
      Accordingly, OPG could be a strong candidate gene for susceptibility to human
      osteoporosis. Here, we analyzed whether OPG is involved in the etiology of
      osteoporosis using both linkage and association analyses. We recruited 164 sib
      pairs in Gunma prefecture, which is located in the central part of Honshu
      (mainland Japan), for a linkage study, and 394 postmenopausal women in Akita
      prefecture, which is in the northern part of Honshu, for an association study. We
      identified two microsatellite polymorphisms in the linkage study, and six single
      nucleotide polymorphisms (SNPs) in the OPG region for the association study.
      Although, no evidence of significant linkage between OPG and osteoporosis was
      found, a possible association of one SNP, located in the promoter region of the
      gene, was identified. A haplotype analysis with the six SNPs revealed that four
      major haplotypes account for 71% of the alleles in the Japanese population.

PMID- 12181641
TI  - Two novel mutations and coexistence of the 991C>T and the 1339C>T mutation on a
      single allele in the coproporphyrinogen oxidase gene in Swedish patients with
      hereditary coproporphyria.
AB  - Hereditary coproporphyria (HCP) is an autosomal dominant disorder, resulting from
      a partial deficiency of the enzyme coproporphyrinogen oxidase (CPO). This enzyme
      catalyzes the sixth step of the heme biosynthetic pathway, and mutations in the
      CPO gene have been coupled to HCP. The present study was undertaken to identify
      disease-producing mutations in the CPOgene in nine Swedish families with HCP.
      Exon 1 of the CPO gene of the nine probands was analyzed directly by sequencing,
      and exons 2-7 were screened by denaturating gradient gel electrophoresis,
      followed by sequencing of exons showing abnormal band pattern. Mutations were
      detected in five of the nine families. In two of these families, the novel
      mutations 623C>T (S208F, exon 2) and 982C>T (R328C, exon 5) were identified,
      respectively. In the affected members of the other three families, the previously
      reported mutations 991C>T (R331W, exon 5) and 1339C>T (R447C, exon 7) were shown
      to coexist on one allele. The present study contributes 2 novel mutations to the
      34 that have been previously reported to cause HCP. In addition, this is the
      first report on patients carrying two HCP-coupled mutations on one allele.

PMID- 12181642
TI  - The role of vitamin D receptor gene polymorphisms in the susceptibility to
      prostate cancer of a southern European population.
AB  - Epidemiological data indicate a relationship between ultraviolet radiation,
      vitamin D, and prostate cancer risk. Antiproliferative effects of vitamin D
      require the expression of the nuclear vitamin D receptor (VDR). A three-fold
      increase in prostate cancer risk associated with the less active vitamin D
      receptor allele (the T allele from VDR TaqI polymorphism at codon 352) was
      reported. The role of VDR genotypes in the susceptibility to prostate cancer has
      not yet been studied in populations of southern Europe. In the present study, we
      determined VDR TaqI genotypes in Portuguese prostate cancer cases ( n = 163) and
      controls ( n = 211), a southern European population. When cases were compared
      with controls, we found an association of VDR T allele with prostate cancer risk
      (odds ratio [OR] = 1.87, 95% confidence interval [CI] 1.02-3.37; P = 0.035). This
      association was confirmed using logistic regression analysis (OR = 2.11, 95% CI
      1.15-3.88; P = 0.015) and in particular associated to risk of prostate cancer
      onset in men over the age of 66 years (OR = 2.36, 95% CI 1.05-5.29; P = 0.036).
      Fifty percent of cases older than 66 years could be attributed to the influence
      of this risk factor. Our results indicate that the contribution of VDR genotypes
      to prostate cancer susceptibility might depend on the population studied and its
      geographic localization, and that VDR genotypes are important in the definition
      of the genetic risk profile of populations of southern Europe.

PMID- 12181643
TI  - 906 variations among 27 genes encoding cytochrome P450 (CYP) enzymes and aldehyde
      dehydrogenases (ALDHs) in the Japanese population.
AB  - We screened DNAs from 48 Japanese individuals for single-nucleotide polymorphisms
      (SNPs) in genes encoding 13 cytochrome P450 (CYP) enzymes and 14 aldehyde
      dehydrogenases (ALDHs) by directly sequencing their entire genomic regions except
      for repetitive elements. This approach identified 810 SNPs and 96
      insertion/deletion polymorphisms among the 27 genes. Of the 810 SNPs, 229 were
      identified among the CYP genes and 581 in the ALDH genes; of the total, 48 SNPs
      were located in 5' flanking regions, 619 in introns, 91 in exons, and 52 in 3'
      flanking regions. These variants should contribute to studies designed to
      investigate possible correlations between genotypes and phenotypes of disease
      susceptibility or responsiveness to drug therapy.

PMID- 12181644
TI  - Identification of polymorphisms in the human SHP1 gene.
AB  - Because mutations in human SHP1 underlie obesity and diabetes, SHP1 is a
      candidate gene for human lipodystrophy syndromes. To identify possible disease
      mutations and/or common single-nucleotide polymorphisms (SNPs), we developed
      primer pairs to amplify the promoter and coding region of SHP1. We used these
      pairs to sequence SHP1 in lipodystrophy patients who had no mutations in known
      lipodystrophy genes, and also in normal control subjects. We found no rare SHP1
      coding sequence variants that were exclusive to patients with lipodystrophy.
      However, we found four polymorphisms, namely, an SNP [-394]C>T in the promoter, a
      micro-deletion polymorphism [-195]delCTGA in the promoter, a missense SNP 541G>C
      in exon 1 (which changed the amino acid sequence G171A), and an SNP 903C>T in
      exon 2. The findings suggest that SHP1 mutations are not commonly seen in
      patients with lipodystrophy who had no mutations in known disease genes. However,
      the identification of amplification primers and polymorphisms provides tools to
      further investigate SHP1 for association with other phenotypes.

PMID- 12181645
TI  - A microarray-based method for detecting methylated loci.
AB  - CpG island DNA methylation plays an important role in regulating gene expression
      in development and carcinogenesis. We developed a new microarray-based method
      called methylation amplification DNA chip (MAD) for detecting differences in
      methylation. In this method, only methylated CpG islands from the two samples
      that we wanted to compare were amplified and used for hybridization. The resource
      material for the microarray was derived from the methylated DNA library of the
      sample in which we wanted to detect hypermethylation. Choosing the methylated DNA
      library as the resource material of the microarray increased the percentage of
      DNA fragments derived from hypermethylated loci on the microarray.

PMID- 12181646
TI  - Wilson disease.
AB  - Wilson disease is an autosomal recessive inherited disorder of copper metabolism,
      characterized by the accumulation of copper in the body due to defective biliary
      copper excretion from hepatocytes. Recently, novel components involved in copper
      metabolism, including Menkes disease protein (ATP7A), Wilson disease protein
      (ATP7B), and copper chaperones, have been identified. It has been demonstrated
      that ATP7B functions in copper secretion into the plasma, coupled with
      ceruloplasmin synthesis and biliary copper excretion. However, the precise
      intracellular localization of ATP7B has been disputed. Various mutations of ATP7B
      have been reported in patients with Wilson disease, and investigations of
      genotype-phenotype correlations are now being conducted in the patients. These
      recent findings provide us with information on the molecular pathogenesis of
      Wilson disease, as well as the biological mechanisms of copper homeostasis. In
      this review, recent advances in this field are briefly summarized.

PMID- 12181648
TI  - Cellular and molecular events leading to renal tubulointerstitial fibrosis.
AB  - Connective tissue remodeling of the extracellular matrix (ECM) is an essential
      and dynamic process associated with both physiological responses, such as wound
      healing, and pathological conditions, such as renal tubulointerstitial fibrosis
      (TIF). Data from the published literature indicate that collagens and several non
      collagenous ECM glycoproteins actively contribute to TIF. The early phase of TIF
      is usually associated with an inflammatory process mediated by soluble factors
      released by activated resident cells and by infiltrating cells. Fibrogenic
      cytokines and growth factors secreted by inflammatory cells and fibroblasts are
      actively involved in connective tissue remodeling, possibly by regulating the
      rate of synthesis and degradation of the ECM. An uncontrolled balance of this
      process usually results in TIF. We review the physiology of wound healing and the
      pathology of fibrosis, emphasizing TIF.

PMID- 12181649
TI  - Electron-dense deposition patterns and the outcomes of idiopathic membranous
      nephropathy in Japanese.
AB  - A considerable diversity in prognosis is seen with membranous nephropathy (MN).
      In terms of pathological findings, the presence of tubulointerstitial lesions was
      emphasized as a poor prognostic factor. However, the glomerular factors affecting
      the long-term outcome of idiopathic human MN have remained unclear. We reviewed
      the initial clinicopathological factors affecting the primary and secondary
      outcomes in 105 patients with primary MN, as well as reviewing previous reports.
      Based on electron microscopic (EM) findings, we could divide patients into two
      subtypes and one subgroup; i.e., homogeneous type with a synchronous phase of
      electron-dense deposits, with large dense deposits (deep subgroup) and
      heterogeneous type with various phases of dense deposits. The homogeneous type
      showed no endstage renal failure, and had earlier remission as compared with the
      heterogeneous type. For the secondary outcome, heterogeneous type and deep
      subgroup were also independent risk factors. However, there was no significant
      difference in the final primary or secondary outcome for any treatment subgroups.
      These results indicated that our category of EM findings was a beneficial marker
      of the primary and secondary outcomes in MN; the homogeneous type of MN with
      synchronous phase of electron-dense deposits (except for the "deep" subgroup) had
      a good outcome.

PMID- 12181650
TI  - Transformation of interstitial fibroblasts and tubulointerstitial fibrosis in
      diabetic nephropathy.
AB  - The developmental mechanism of tubulointerstitial fibrosis in diabetic
      nephropathy (DN) has not been elucidated. Tubulointerstitial fibrosis, as well as
      glomerulosclerosis, occurs in DN. Myofibroblasts which overproduce extracellular
      matrix are present in the renal interstitium in diabetics, although they are
      almost never seen in normal kidneys. The myofibroblasts appear to originate from
      interstitial fibroblasts. In addition, transforming growth factor-beta1 (TGF-beta
      1), which can evoke myofibroblast transformation, is detected in interstitial
      cells in the diabetic kidney, but not in the normal kidney. Taken together, these
      findings led us to speculate that TGF-beta 1 induces the transformation of
      interstitial fibroblasts into myofibroblasts, followed by tubulointerstitial
      fibrosis. Based on this speculation, we discuss the developmental mechanism of
      tubulointerstitial fibrosis in this review.

PMID- 12181651
TI  - Ultrastructural and cytochemical characterization of human cord blood cells.
AB  - As part of a study to identify the characteristics of cord blood cells, we
      examined their morphological features by electron microscopy. Additionally, we
      cultured CD34-positive cells derived from cord blood and from bone marrow to
      perform morphological observations, as well as cytochemical examinations
      following the peroxidase reaction. Compared with normal peripheral blood cells,
      cord blood cells frequently showed immature morphology and a unique
      ultrastructure, such as nuclear pockets in neutrophils, several crystalloids in a
      single eosinophilic granule, and deformed nuclei in lymphocytes. In contrast to
      bone marrow cells, cord blood cells yielded a large number of cells of immature
      myelo-monocytic lineages in cell culture, and demonstrated a weaker peroxidase
      reaction. We identified that cord blood cells were different from normal
      peripheral blood cells and bone marrow cells, confirming the functional
      differences that were previously assumed.

PMID- 12181652
TI  - Synovial sarcoma arising from the pleura: a case report with ultrastructural and
      immunohistological studies.
AB  - Synovial sarcoma commonly occurs in the para-articular regions of the
      extremities, and rarely in the pleura. We report a 46-year-old woman with primary
      synovial sarcoma of the pleura. She was admitted with a complaint of left-sided
      chest pain and exertional dyspnea. She had previously undergone two operations
      for pleural neoplasm, at the ages of 33 and 36 years. A computed tomography scan
      revealed an expanded mass in the left thoracic cavity, involving the surrounding
      tissue. Macroscopic findings demonstrated a 25 x 25 x 15-cm grayish-white mass
      with hemorrhage beneath the pleura. Both epithelial and spindle cells were
      observed microscopically. Ultrastructural microscopy of the epithelioid cells
      demonstrated short, blunt microvilli on the luminal surface, and desmosomes
      between the neoplastic cells. Immunohistochemically, the tumor cells of the
      epithelial component were positive for embryonal membrane antigen (EMA),
      carcinoembryonic antigen (CEA), human mesothelial cells (HBME)-1, and
      cytokeratin, and the spindle cells were positive for vimentin. These findings led
      us to a diagnosis of primary synovial sarcoma of the pleura. She had no evidence
      of recurrence or metastasis after the third operation.

PMID- 12181654
TI  - The 17th annual research meeting of the Japanese orthopaedic association.

PMID- 12181653
TI  - An ultrastructural study of calcifying odontogenic cyst, especially calcified
      material.
AB  - The ultrastructural features of calcification in a case of calcifying odontogenic
      cyst (COC) were studied. Scanning electron microscopic examination of the inner
      parts of the cyst wall revealed many short microvilli, and X-ray microanalysis of
      the high-density masses in the intercellular parts showed prominent calcium
      peaks, which meant that these masses were calcified materials. On transmission
      electron microscopic observations, many calcifications exhibited a distinctive
      ring formation around the periphery of a central core that consisted of an
      amorphous structure. These calcifications were observed with necrotic remnants of
      nuclear material and many identifiable mitochondria, thin fibers, and epithelial
      cells. The cytoplasm of ghost cells consisted of numerous short electron-dense
      tonofilament bundles. Needle-like structures were shown in the tonofilament
      bundles. X-ray diffraction analysis showed that the needle-like crystals were
      hydroxyapatite. It is suggested that calcification in a COC may be related to
      degenerative mitochondria and tonofilament bundles of ghost cells.

PMID- 12181655
TI  - CT image evaluation of the internal rotation limit prior to bony impingement
      after total hip arthroplasty.
AB  - This study evaluated the internal rotation limit prior to bony impingement of the
      proximal femur on the pelvis after total hip arthroplasty (THA). Reconstructed
      computed tomography (CT) images of 90 degrees hip flexion were used to simulate
      the internal rotation limit against safety limits measured intraoperatively.
      Ninety joints in 86 subjects (12 men and 74 women) underwent THA for the
      treatment of secondary coxarthrosis. The correlation between the internal
      rotation limit prior to the bony impingement intraoperatively and the simulated
      internal rotation angle on the reconstructed CT image was statistically
      significant. We provide a new method to simulate the internal rotation limit
      prior to bony impingement based on postoperative CT.

PMID- 12181656
TI  - Vascular compression caused by solitary osteochondroma: useful diagnostic methods
      of magnetic resonance angiography and Doppler ultrasonography.
AB  - Osteochondroma is a common benign bone tumor that sometimes causes vascular
      complications when the lesion is situated near the knee. Venous complications are
      seen less frequently. We report two cases of solitary osteochondroma that arose
      in the distal femur. The patients were an 11-year-old boy and a 16-year-old boy,
      both of whom were suffering from bone protuberance and lower leg swelling due to
      congestion. In both patients, magnetic resonance imaging (MRI) revealed dilated
      popliteal veins at a site distal from the tumors or superficial veins. MR
      angiography (MRA) showed compressed popliteal arteries, and Doppler
      ultrasonography revealed weaker blood flow in the dorsalis pedis arteries in the
      lower leg with the tumor than in the other lower leg. The former patient
      complained of pain due to swelling in the lower leg, and for this reason the
      patient underwent resection of the tumor. After resection, both the swelling and
      the pain were decreased, and Doppler ultrasonography also revealed normal blood
      flow in the artery. The latter patient had swelling, but no pain, in the lower
      leg, and accordingly this patient has been followed carefully without resection,
      since there is always the possibility of irreversible vascular damage caused by
      osteochondroma, such as arterial or venous occlusion. We present two patients
      with osteochondroma, both of whom suffered from swelling of the lower leg due to
      venous compression by the tumor. In both cases, MRI and MRA were useful to show
      the presence of vascular compression. Doppler ultrasonography could also reveal
      the blood flow disturbance objectively, even in current osteochondroma cases in
      which there were no arterial symptoms.

PMID- 12181658
TI  - Augmentation with a Gore-Tex patch for repair of large rotator cuff tears that
      cannot be sutured.
AB  - The objective of this study was to determine the effectiveness of augmentation
      with a Gore-Tex patch in reconstruction of rotator cuff tears that cannot be
      repaired by direct suture. Twenty-eight shoulders of 27 patients underwent this
      procedure. The average age at surgery was 62 years, the average duration of
      symptoms before surgery was 16 months, and the average follow-up period was 44
      months. The shoulders were classified into two groups according to patch size
      (anteroposterior dimension up to 2 cm or greater than 2 cm). The clinical outcome
      was evaluated by using the shoulder surgery classification system issued by the
      Japanese Orthopaedic Association (JOA score), and the postoperative isometric
      abduction strength at 90 degrees of abduction was assessed by the method of
      Constant. The average total JOA score improved from 57.7 to 88.7 points, a
      statistically significant change. There was no difference in the improvement in
      score between shoulders treated with small patches (12 shoulders) and those
      treated with large patches (16 shoulders). The average abduction strength was 6.2
      kg in the small-patch group and 1.5 kg in the large-patch group, with a
      statistically significant difference between the two groups. Good clinical
      results, especially pain relief, could be achieved with this procedure in both
      the small- and the large-patch groups, but good abduction strength was obtained
      only in the small-patch group. The mechanism of the improvement by this procedure
      is still controversial.

PMID- 12181657
TI  - Changes in LPIA D-dimer levels after total hip or knee arthroplasty relevant to
      deep-vein thrombosis diagnosed by bilateral ascending venography.
AB  - The purpose of the current retrospective study was to determine the most
      sensitive and specific cutoff value of plasma D-dimer level associated with deep
      vein thrombosis (DVT) after total hip (THA) or knee (TKA) joint arthroplasty.
      Diagnosis of DVT was determined by bilateral ascending venography pre- and
      postoperatively. Plasma D-dimer levels were measured by a latex photometric
      immunoassay system (LPIA) preoperatively and postoperatively on days 1, 3, 7, 10,
      14, and 21. Postoperative DVT diagnosed by venography was found in 22 patients
      (40.1%) after THA and in 18 patients (64.3%) after TKA. Plasma D-dimer levels
      were significantly higher ( P < 0.01) in patients with DVT than in those without
      DVT on days 1, 7, and 10 after THA, but only on day 7 after TKA. Statistical
      analysis confirmed that a cutoff value of 10.0 microg/ml for D-dimer on day 7 was
      most sensitive (THA, 95.5%; TKA, 94.4%) and most specific (THA, 96.9%; TKA,
      90.0%) in the diagnosis of DVT after THA as well as TKA. It was concluded that
      over 10 microg/ml of LPIA D-dimer on postoperative day 7 appears to be an
      indication of the occurrence of DVT after THA and TKA.

PMID- 12181659
TI  - Aggressive active mobilization following zone II flexor tendon repair using a two
      strand heavy-gauge locking loop technique.
AB  - In vitro and in vivo experimental studies have shown that a new two-strand
      technique increases the tensile strength of flexor tendon repair and eliminates
      gap formation at the healing repair site. The purpose of the current study was to
      clinically evaluate the new technique, followed by an aggressive active
      mobilization program. Seven digits with zone II flexor tendon lacerations were
      treated using the technique, employing a heavy (2-0) braided polyester suture.
      The patients were encouraged to perform active mobilization of the injured digits
      by themselves with almost a full range of flexion and extension after they were
      instructed by the surgeon for few days from the first postoperative day. All
      patients were followed up for at least 6 months, except for one, with whom
      contact was lost in 14 weeks postoperatively. Six of the seven digits were
      evaluated as excellent in 6 months by the original Strickland criteria, thus
      showing that the combination of the new repair technique and aggressive active
      mobilization is effective for zone II flexor tendon repair.

PMID- 12181660
TI  - Epithelioid sarcoma of the extremities: a dismal long-term outcome.
AB  - Epithelioid sarcoma is a rare histologic subtype of sarcoma. The clinical
      behavior and prognostic factors influencing survival in this disease are
      examined. A review of clinicopathologic features of patients with epithelioid
      sarcoma prospectively followed between September 1981 and April 2001 at the
      Cancer Institute Hospital was performed. Eight patients (4 men and 4 women)
      constituted the subjects of this study, with a mean age of 41 years. Tumors
      presented in the lower extremity in 62.5% of patients and in the upper extremity
      in 37.5%. All patients were followed for at least 10 years from the time of
      diagnosis or until death. The follow-up ranged from 17 to 228 months, with a mean
      of 78 months. At least one local recurrence was seen in 50% of patients. During
      the course of the disease, metastases to regional lymph nodes developed in 50% of
      patients and metastases to the lungs in 62.5%. The median survival was 31 months,
      with a 25% 5-year and 10-year survival rate. Pulmonary metastases were correlated
      with decreased survival. A delay in diagnosis of epithelioid sarcoma is common.
      Epithelioid sarcoma differs from other sarcoma subtypes in its propensity for
      nodal spread and local recurrence. Chemotherapy and radiotherapy have an
      insignificant effect on the course of epithelioid sarcoma. Careful follow-up,
      evaluating local recurrence, nodal spread, and pulmonary metastases, is
      warranted. The long-term outcome of epithelioid sarcoma is dismal.

PMID- 12181661
TI  - Bipolar revision arthroplasty for failed threaded acetabular components:
      radiographic evaluation of cup migration.
AB  - We studied the radiographic results of bipolar revision hip arthroplasty in 25
      patients (25 hips). These patients had suffered from osteoarthrosis of the hip
      due to acetabular dysplasia and had undergone total hip replacement using smooth
      threaded acetabular components. In the revision surgery, these components were
      replaced by bipolar cups; autografts were implanted in 23 patients and
      hydroxyapatite grains were added in 7. At the time of follow-up, the severity of
      migration was radiographically graded from I to IV: grade I, 5 mm or less; grade
      II, 6 to 10 mm; grade III, 11 to 15 mm; and grade IV, 16 mm or more. Five to 11
      years (average, 7.0 years) after surgery, 9 patients were classified as grade I,
      6 as grade II, 4 as grade III, and 6 as grade IV. Among the 6 individuals with
      grade IV migration, hydroxyapatite grains had been used in 5. There was a
      significant negative correlation between the distance of migration and the
      increase in size of the threaded acetabular components used in the primary total
      hip replacement and the bipolar cups in the revision surgery. Because of the
      tendency to migrate, we concluded that this procedure has a limited role in
      revision surgery.

PMID- 12181662
TI  - Femoral shaft fracture callus formation after intramedullary nailing: a
      comparison of interlocking and Ender nailing.
AB  - Intramedullary nailing is widely used for the operative treatment of femoral
      fractures. Recently, the biologic healing of fractures has become better
      understood from fundamental investigations. However, there has been no clinical
      comparison between the fracture healing process with these two fixation methods.
      The purpose of this study was to use radiographs to compare callus formation with
      two types of intramedullary nailing for femoral shaft fractures: reamed
      interlocking (IL) nails and Ender nails. Femoral shaft type A fractures (AO
      classification) were studied. Twenty-seven fractures were treated with reamed IL
      nailing, and 81 fractures were treated with Ender nailing. The callus area was
      calculated from the maximum cross-sectional area on the anteroposterior and
      lateral radiographs. The callus appeared at a mean of 3.9 weeks after surgery in
      the IL group, and at a mean of 2.8 weeks in the Ender group ( P < 0.05). In the
      IL and Ender groups, fracture healing was noted at a mean of 3.4 and 2.0 months,
      respectively. The mean area of callus formation in the IL and Ender nailing
      groups was 439.5 mm(2) and 699.4 mm(2), respectively ( P < 0.02). Ender nailing
      results in abundant callus, which forms at an earlier stage after the procedure
      than in patients treated with IL nailing. Dynamization at the fracture site is
      reported to increase external callus formation. Our results indicate that the
      elasticity of the fixation obtained with Ender nailing promotes callus formation.

PMID- 12181663
TI  - High-dose chemotherapy and autologous peripheral blood stem-cell transfusion
      after conventional chemotherapy for patients with high-risk Ewing's tumors.
AB  - Although the overall results of treatment of Ewing's tumors have improved,
      patients with high-risk factors, including metastatic disease at diagnosis, bulky
      primary tumors, axial sites, and age >15 years, continue to have poor prognoses.
      The effects of high-dose chemotherapy and autologous peripheral blood stem-cell
      transplantation on high-risk Ewing's tumor patients have been reported. In most
      of these studies, conditioning and high-dose regimens varied among patients. Here
      we report the feasibility and effects of a high-dose chemotherapy regimen
      conducted in our institution. Seven patients with high-risk Ewing's tumors were
      treated by high-dose chemotherapy. The patients received four cycles of remission
      induction chemotherapy, and then peripheral blood stem cells were mobilized by
      high-dose etoposide and harvested. Myeloablative chemotherapy consisted of
      carboplatin, ifosfamide, and etoposide. The patients have 5-year overall and
      relapse-free survival probabilities of 0.86 and 0.81, respectively. The results
      were significantly better than those for patients treated with conventional
      chemotherapy alone. None of the patients had severe side effects. The high-dose
      regimen and transplantation were feasible and well tolerated. The poor prognoses
      of high-risk Ewing's tumor patients may be improved by high-dose chemotherapy
      with peripheral blood stem cell transplantation. However, the real impact of the
      therapy on the clinical outcome of patients with high-risk Ewing's tumors should
      be evaluated in a prospective, randomized study.

PMID- 12181664
TI  - Quantitative analysis of the effect of lumbar orthosis on trunk muscle strength
      and muscle activity in normal subjects.
AB  - We studied the effect of lumbar orthosis on trunk muscle strength and muscle
      activity during flexion-extension bending of the trunk in 31 male volunteers.
      Trunk muscle strength was measured with a kinetic measurement system. Peak torque
      was calculated by using the mean torque of five repetitions. Trunk muscle
      activity was measured with commercially available equipment that has portable EMG
      data-collection units. The maximum level of the EMG signal was evaluated by
      employing the analyzing part of the computer's measuring program. With the
      application of the lumbar orthosis, the strength of the abdominal muscle and the
      back muscle increased; conversely, the activities of both muscles were decreased
      significantly. This might imply that lumbar orthosis reduces the load of the
      trunk muscles during performance.

PMID- 12181665
TI  - Intramuscular bone induction by human recombinant bone morphogenetic protein-2
      with beta-tricalcium phosphate as a carrier: in vivo bone banking for muscle
      pedicle autograft.
AB  - An ideal replacement for bone defects is auto-bone tissue, of which there is an
      ample supply with the required form and with vascularity. Our strategy for
      generating such bone tissue is as follows. First, bone tissue is induced in
      muscle by bone morphogenetic protein-2 (BMP-2) with beta-tricalcium phosphate as
      a carrier to maintain its form in the muscle. Second, the induced bone in the
      muscle pedicle is grafted to the bone defect to maintain vascularity. In the
      first experiment, 50 microg of recombinant human BMP-2 (rhBMP-2) was inoculated
      into the hip abductor muscle of rabbits with beta-tricalcium phosphate under
      anesthesia. Five weeks after the operation, intramuscular bone formation was
      observed in all of the samples, and the form and size of the induced bone tissue
      were identical to those of the carrier. Ten weeks after the operation, the
      induced bone was partly absorbed. In the second experiment, 50 microg of rhBMP-2
      was inoculated in the same manner as previously. Five weeks after the operation,
      the muscle tissue around the induced bone was incised, leaving just the proximal
      part as a pedicle. Two or four weeks after the second operation, the induced bone
      tissue had rich vascularity and no empty lacunae. This indicates the possibility
      of in vivo bone banking to enable morphologically controlled and vascularized
      auto-bone grafts.

PMID- 12181666
TI  - T1-2 disc herniation following an en bloc cervical laminoplasty.
AB  - We report a rare case of T1-2 disc herniation following cervical laminoplasty. A
      56-year-old male patient presented with left foot-drop and gait disturbance of
      abrupt onset 11 years after a successful laminoplasty from C3-7. Magnetic
      resonance imaging revealed spinal stenosis at T1-2 due to intervertebral disc
      herniation and ligamentum flavum hypertrophy. Three days later, laminectomy with
      disc fragment excision was performed at that level. Two weeks after surgery, he
      was able to walk without assistance. Mechanical stresses may have directly
      affected the T1-2 intervertebral disc following laminoplasty and may have caused
      disc herniation.

PMID- 12181667
TI  - Case report of a Cushing's syndrome patient with multiple pathologic fractures
      during pregnancy.
AB  - We describe a case of multiple pathologic fractures in a woman with Cushing's
      syndrome during pregnancy. Pathologic fractures were seen in the pubic and
      ischial bones and in T12 and L1 of the vertebral body. These findings,
      accompanied by easy fatigue, amenorrhea without nursing, psychological disorder,
      and premature birth, were retrospectively compatible with those of Cushing's
      syndrome, not pregnancy-associated osteoporosis. After adrenalectomy, the pain in
      her groin and back ceased. Plain radiographs showed healing of the fractures and
      increased mineralization. This case demonstrates the need to be alert to the
      possible presence of metabolic bone disease, including Cushing's syndrome, when
      we encounter multiple pathologic fractures with osteoporosis in young patients,
      even if the patient is pregnant.

PMID- 12181668
TI  - Solitary lymphangioma of the femur. A case report.
AB  - Lymphangioma of the bone is a benign lesion, characterized by newly formed lymph
      vessels. It usually occurs in a diffuse manner or as multiple lesions. Solitary
      lymphangioma of the bone is an extremely rare condition. We herein describe a
      case of solitary lymphangioma of the femur in a 55-year-old woman who presented
      with knee pain. Radiographs showed an eccentric osteolytic lesion in the distal
      femur. This is the first reported case of solitary lymphangioma of the bone
      occurring in the femur.

PMID- 12181669
TI  - Hydatid disease at the proximal end of the clavicle.
AB  - We report a case of hydatid disease at the proximal end of the clavicle of a 47
      year-old woman. In an open biopsy, laminated layers, characteristic of
      Echinococcus multilocularis larvae, were revealed by periodic acid-Schiff (PAS)
      staining. A marked foreign-body reaction was observed in the pathological
      findings. The patient was definitely diagnosed as having osseous hydatid disease.
      We performed resection of the infected part of the clavicle, and after the
      operation, she has been cured under medication with albendazole for 9 years, with
      no finding of recurrence in the clavicle.

PMID- 12181671
TI  - Phycodnaviridae--large DNA algal viruses.
AB  - Members and prospective members of the family Phycodnaviridae are large
      icosahedral, dsDNA (180 to 560 kb) viruses that infect eukaryotic algae. The
      genomes of two phycodnaviruses have been sequenced: the 331 kb genome of
      Paramecium bursaria chlorella virus (PBCV-1) and more recently, the 336 kb genome
      of the Ectocarpus siliculosus virus (EsV-1). EsV-1 has approximately 231 protein
      encoding genes whereas, the slightly smaller PBCV-1 genome has 11 tRNA genes and
      approximately 375 protein-encoding genes. Surprisingly, the two viruses only have
      33 genes in common, of which 17 have no counterparts in the databases. The low
      number of homologous genes between the two viruses can probably be attributed to
      their different life styles. PBCV-1 is a lytic virus that infects a unicellular,
      endosymbiotic freshwater green alga whereas, EsV-1 is a lysogenic virus that
      infects a free-living filamentous marine brown alga. Furthermore, accumulating
      evidence indicates that the phycodnaviruses and their genes are ancient, thus
      allowing significant differences to have evolved. This review briefly describes
      some of the biological properties of the phycodnaviruses, focusing on PBCV-1 and
      EsV-1, and then compares their genomes.

PMID- 12181670
TI  - Recent progress in flexor tendon healing.
AB  - Although advances in the treatment of flexor tendon injuries have led to improved
      clinical outcomes during the past several decades, a subset of patients continue
      to experience a loss of function. Using a canine model of sharp transection of
      the flexor digitorum profundus tendon followed by repair and rehabilitation using
      clinically relevant techniques, we have examined the influence of multistrand
      suture and postoperative rehabilitation variables on digital function and tendon
      strength. Our findings highlight the critical role of repair technique in
      providing a stiff and strong repair and indicate that continued refinement of
      suture techniques is warranted in order to minimize repair-site elongation (gap).
      Gap formation continues to occur at a high frequency, and the formation of gaps
      greater than 3 mm delays the accrual of repair-site strength that occurs with
      time. Furthermore, our results indicate that passive-motion rehabilitation that
      produces a moderate amount of tendon excursion (2 mm) at low levels of tendon
      force (5 N) is sufficient to inhibit adhesion formation and to promote healing.
      Increases in excursion or force beyond these levels do not accelerate the healing
      process. These findings suggest that we are approaching the limit of the extent
      to which we can modulate healing by manipulating rehabilitation variables such as
      tendon excursion and force. Future advances will probably require manipulation of
      the biological factors that promote healing.

PMID- 12181672
TI  - CD8+ T cells from feline immunodeficiency virus (FIV) infected cats suppress
      exogenous FIV replication of their peripheral blood mononuclear cells in vitro.
AB  - Feline immunodeficiency virus (FIV) isolates from domestic cats have been
      classified into five subtypes, designated A, B, C, D and E. Although many FIV
      infected cats may have frequent contact with multiple strains of FIV, they
      usually become infected with a single FIV subtype. In the present study, we
      demonstrate that peripheral blood mononuclear cells (PBMC) of FIV infected cats
      were resistant to exogenous FIV (second virus) replication in vitro and that the
      resistance of these PBMC was mediated by CD8+ T cells. In cats with a low anti
      FIV activity of CD8+ T cells, the proviral DNA of the second virus inoculated
      into PBMC was detected intracellularly, and both the second and the originally
      infecting strain (original virus) were produced in the culture supernatant. In
      contrast, in cats with a high anti-FIV activity of CD8+ T cells, both the
      proviral DNA of the second virus and the original virus were detected in PBMC
      intracellularly, but neither virus was produced in the culture supernatant.
      However, when PBMCs from these cats were depleted of CD8+ T cells, the RNA of
      both viruses was detected in the culture supernatant. These results suggest that
      CD8+ T cells inhibit the late phase of FIV replication after viral integration.
      Moreover, the inhibition was also effective against FIV strains of different
      subtypes from that of the original strain. It appears that the CD8+ T cell
      mediated immune response plays important roles in the maintenance of an
      asymptomatic state in FIV-infected cats and their resistance to superinfection.

PMID- 12181673
TI  - Immunophilins and HIV-1 infection.
AB  - Peptides of the V3 loop of the HIV-1 envelope glycoprotein gp120 have been shown
      to bind with high affinity to the immunophilins cyclophilin (Cyp) A, CypB and the
      FK506-binding protein 12 (FKBP12) [10]. We investigated whether immunophilins
      affect HIV-1 infection by assuming they are able to bind to the V3 loop of gp120.
      T cells and peripheral blood mononuclear cells were infected with T-cell-tropic
      or macrophage-tropic HIV-1 strains, respectively, in the presence of different
      concentrations of immunophilins. P24 antigen ELISA and real-time PCR measurements
      demonstrated that exogenously added immunophilins do not influence HIV-1
      infection. CypA is known to interact with the HIV-1 Gag polyprotein and to be
      incorporated into the virions. This incorporation can be prevented by cyclosporin
      A (CsA) resulting in a decreased yield of infectious virus, the mechanism of
      which is unknown. We measured a normal production of proviral DNA in the first
      round of infection in CsA treated cells but afterwards, infection was decreased
      if CsA was present. Pre-treatment of the HIV-1 inocula with CsA, blocking the
      function of virus-associated CypA, did not inhibit the ensuing yield of
      infection. We therefore may conclude that endogenous CypA exerts its action after
      reverse transcription but before virus maturation, probably during capsid
      formation. FK520, an immunosuppressor which binds to FKBP, had no effect on HIV-1
      infection.

PMID- 12181674
TI  - Synthesis and expression of viral antigens in Vero cells persistently infected
      with Junin virus.
AB  - Two Vero cell lines persistently infected with XJCl3 and Cl67 strains of Junin
      virus and named V3 and V7, respectively, have been characterized with respect to
      the presence and expression of the nucleoprotein (N) and the glycoprotein
      precursor (GPC) viral genes. After the acute phase of infection, where a marked
      CPE and high titers of virus were obtained, JV persistently infected cells became
      morphologically undistinguishable from Vero cells and virus production dropped to
      undetectable levels. V3 and V7 were resistant to the superinfection with
      antigenically related viruses. This fact could not be attributed to the presence
      of defective interfering particles or non-infectious virus in the supernatant.
      Expression of N was consistently detected in both cultures and accumulation of
      two degradation products of N was evident during the late passages. Although no
      G1 (main surface glycoprotein) expression was observed, a marked fusogenic
      capacity was detected in both cultures indicating at least, the synthesis of a
      GPC derived fusogenic glycoprotein. Cell lysates from V3 and V7 subjected to RT
      PCR, using specific primers for N gene, or to a nested RT-PCR using specific
      primers for GPC (G1 region) confirmed the presence of both viral genes. No viral
      DNA sequences could be detected in JV persistently infected cells.

PMID- 12181675
TI  - Folding of the rabbit hemorrhagic disease virus capsid protein and delineation of
      N-terminal domains dispensable for assembly.
AB  - Rabbit hemorrhagic disease virus (RHDV) and European brown hare syndrome virus
      (EBHSV) are caliciviruses that produce severe symptoms and are lethal to rabbits
      and hares. The folding of the capsid protein was studied by determination of the
      antigenic pattern of chimeric capsid proteins, composed of regions from RHDV and
      EBHSV capsid proteins. The anti-RHDV monoclonal antibody (MAb) E3, which is known
      to bind an external conformational epitope, recognized the RHDV C-terminal
      region. The anti-RHDV MAb A47, which binds a buried epitope, recognized the RHDV
      N-terminal region. Using a pGEX expression library, we more precisely mapped the
      MAb A47 epitope on a 31 residues length peptide, between residue 129 and 160 of
      the VP60, confirming its location in the N-terminal part of the protein. These
      results demonstrate that the C-terminal part of the protein is accessible to the
      exterior whereas the N-terminal domain of the protein constitutes the internal
      shell domain of the particle. With the aim of using virus-like particles (VLPs)
      of RHDV as epitope carriers or DNA transfer vectors, we produced in the
      baculovirus system three proteins, DeltaN1, DeltaN2 and DeltaN3, truncated at the
      N terminus. The DeltaN1 protein assembled into VLPs, demonstrating that the first
      42 amino acid residues are not essential for capsid assembly. In contrast,
      DeltaN2, from which the first 75 residues were missing, was unable to form VLPs.
      The small particles obtained with the DeltaN3 protein lacking residues 31 to 93,
      located in the immunodominant region of the RHDV capsid protein, indicate that up
      to 62 amino acid residues can be eliminated without preventing assembly.

PMID- 12181676
TI  - The complete sequence of the genome of Cocksfoot streak virus (CSV), a grass
      infecting Potyvirus.
AB  - The complete nucleotide sequence of Cocksfoot streak virus (CSV) has been
      determined. The viral genome comprises 9663 nucleotides, excluding a 3'-terminal
      poly(A) sequence. The genome of CSV has a 133 nt 5'-non coding and a 260 nt 3'
      non coding region. The RNA of CSV encodes a single polyprotein of 3089 amino acid
      residues and has a deduced genome organization typical for a member of the family
      Potyviridae. CSV is transmissible by aphids and has a narrow host range in the
      Gramineae. It was compared to two potyviruses having monocotyledonous hosts
      (monocot potyviruses) and several potyviruses infecting dicotyledonous plants
      (dicot potyviruses). CSV is most closely related to other monocot potyviruses
      like Maize dwarf mosaic virus (MDMV) and Johnson grass mosaic virus (JGMV), but
      also closely related to the dicot potyviruses. On the other hand, CSV is less
      related to monocot viruses from the other genera (Rymovirus, Tritimovirus) within
      the Potyviridae. Specific motifs, described for potyviral polyproteins, are also
      present in the polyprotein of CSV. Only two motifs in the HC-Pro--motif involved
      in long distance movement and motif for HC-Pro self-interaction--were different
      in comparison to most of the dicot potyviruses.

PMID- 12181677
TI  - Hibiscus virus S is a new subgroup II tobamovirus: evidence from its unique coat
      protein and movement protein sequences.
AB  - The coat protein (CP) and movement protein (MP) sequences of a new tobamovirus
      infecting Hibiscus rosa-sinensis L were determined. The CP gene encodes 163 amino
      acid (aa) residues and with a theoretical molecular weight of 18.19 kDa. The MP
      gene encodes 282 amino acids and its theoretical molecular weight is 30.36 kDa.
      The nucleotide (nt) and aa sequences of the CP were 46.88 % to 51.63 % and 45.34
      % to 57.06 % identical to other tobamoviruses, respectively. The nt and aa
      sequence identities of MP ranged from 38.81 % to 43.90 % and 30.85 % to 37.88 %,
      respectively. The predicted virion origin of assembly (OAS) was located in the CP
      gene. Phylogenetic trees generated based on the nt and aa sequences of both CP
      and MP genes indicate that this new virus clusters with members of subgroup II of
      tobamoviruses. Although this hibiscus virus shared a high nt and aa sequence
      identity with Sunn-hemp mosaic virus (SHMV), Western analysis showed that it is
      serologically unrelated to SHMV. We propose the name Hibiscus virus S (HVS) for
      this Singapore isolate. This is the first report on partial nt sequence of a
      tobamovirus that infects hibiscus.

PMID- 12181678
TI  - Phylogeny and geographical differentiation of zucchini yellow mosaic virus
      isolates (Potyviridae) based on molecular analysis of the coat protein and part
      of the cytoplasmic inclusion protein genes.
AB  - DNA sequences for the coat protein (CP) and part of the cytoplasmic inclusion
      (CI) protein genes after reverse transcriptase-polymerase chain reaction (RT-PCR)
      were reported for the first time for isolates of zucchini yellow mosaic virus
      (ZYMV) from Austria, Germany, Italy and Slovenia. Comparison of the DNA sequences
      of 30 isolates from different geographical regions worldwide revealed highest
      similarities of the Austrian isolates to those from Slovenia and Hungary.
      Isolates from Germany and Italy were only distantly related and clustered with
      isolates from other parts of the world. Our results indicate that a specific
      isolate can spread rapidly to geographically adjacent areas but may not be
      directly related to isolates found in other neighboring countries.

PMID- 12181679
TI  - Avian embryo susceptibility to Italian H7N1 avian influenza viruses belonging to
      different genetic lineages.
AB  - In the present paper we report of the results of an immunohistochemical
      investigation to assess tissue tropism and viral replication in developing
      chicken, turkey, Muscovy duck and mallard duck embryos, of Italian H7N1 isolates
      belonging to different genetic lineages. LPAI isolates were chosen on the basis
      of the location in the phylogenetic tree: a progenitor strain,
      A/ty/Italy/977/V99, (exhibiting no additional glycosylation site, nAGS), strain
      A/ty/Italy/2379/V99 (AGS in position 123) and strain A/ty/Italy/3675/V99 (AGS in
      position 149) were selected. The latter two strains belonged to distinct lineages
      originating from the pool of progenitor strains. HPAI isolate A/ty/Italy/4580/V99
      was also included in the study. All the embryos tested supported the growth of
      HPAI. The LPAI isolates replicated readily in the allantoic layer of the CAM of
      all the species tested, and did not grow in the developing chicken, turkey and
      Muscovy duck embryos. In contrast, they replicated to different extents in the
      respiratory tract of the developing mallard embryo, which also presented lower
      mortality rates than the other species. We conclude from these findings that the
      pathogenesis of LPAI infections in mallard embryos is different to that observed
      in other species, and should be investigated further.

PMID- 12181681
TI  - Nucleotide sequence analysis of RNA-2 of a flat apple isolate of Cherry rasp leaf
      virus with regions showing greater identity to animal picornaviruses than to
      related plant viruses.
AB  - RNA-2 of a flat apple isolate of Cherry rasp leaf virus (CRLV-FA) appears to
      consist of 3274 nucleotides, excluding a 3' poly (A) tail. The data supports re
      classification of CRLV in a new genus in the family Comoviridae. A single open
      reading frame (ORF) encoding a putative 108 kDa polyprotein was identified.
      Potential protease cleavage sites were identified which would result in the
      production of a putative movement protein (41 kDa), and 3 capsid protein subunits
      (24, 20, and 22 kDa, respectively). A 5'-UTR and 3'-UTR were identified, 248 nt
      and 146 nt long, respectively. The genome organisation of CRLV-FA RNA-2 is
      similar to that of Apple latent spherical virus (ALSV) RNA-2, a new member of the
      family Comoviridae. The Vp25 amino acid sequences were unique to CRLV-FA and ALSV
      (54% identity), with no relationship identified to any other virus. CRLV-FA Vp20
      and Vp24 amino acid sequences were closely related to ALSV (59 and 65%,
      respectively) but the only other relationships identified were with a range of
      animal ssRNA positive-strand viruses.

PMID- 12181680
TI  - Characterization and identification of Oya virus, a Simbu serogroup virus of the
      genus Bunyavirus, isolated from a pig suspected of Nipah virus infection.
AB  - A virus, named Oya virus, was isolated in Vero cell cultures from the lungs of a
      pig suspected of Nipah virus infection. The virus was revealed as a spherical
      enveloped RNA virus with a diameter of 79 nm. For identification of Oya virus, RT
      PCR was performed. A common primer set for S-RNA of the Simbu serogroup of the
      genus Bunyavirus was able to amplify a cDNA from Oya virus RNA. The sequence data
      of the product revealed that the partial gene of Oya virus S-RNA segment had 65
      70% homology with published cDNA sequences of Simbu serogroup viruses. The
      phylogenetic analysis of the data showed that the Oya virus is grouped in Simbu
      serogroup, but is genetically distinct from the serogroup viruses that have been
      analyzed molecularly. Serological surveys revealed that the virus distributed
      widely and densely in Malaysia.

PMID- 12181682
TI  - Size and sequence variability of the Arabis mosaic virus protein 2A.
AB  - The RNA 2 of the nepovirus Arabis mosaic virus (ArMV) encodes a polyprotein from
      which protein 2A is released by proteolytic cleavage at the N-terminus. The 2A
      gene of 19 ArMV isolates from different geographical origin and 9 distinct
      natural hosts was amplified by RT/PCR and subsequently cloned and sequenced.
      These 19 isolates and those from databanks were classified into four groups based
      on the size of the protein 2A which ranged from 233 to 280 amino acids, and
      sequence identities. Sequence variability was mainly located in the N-terminus of
      the proteins, whereas the core region and the C-terminus were conserved.

PMID- 12181683
TI  - A summary of taxonomic changes recently approved by ICTV.

PMID- 12181684
TI  - Five years experience with gravitational shunts in chronic hydrocephalus of
      adults.
AB  - OBJECTIVE: Gravitational shunts for management of chronic hydrocephalus are
      supposed to avoid or at least to reduce the risk of overdrainage. In order to
      find out if this hypothesis is correct, we did a prospective study and analysed
      the results of a series of 185 hydrocephalic adults, treated by using
      gravitational shunts. For the few cases in whom overdrainage occurred, we wanted
      to establish the reason for it. Especially it should be proven or excluded that
      overdrainage was caused by shortcomings of the principle of gravitational shunts.
      Another goal was to compare post-shunting changes of the ventricular size with
      clinical outcome. A comparably large study has not yet been published. METHODS:
      185 adult patients who suffered from chronic hydrocephalus were shunted between
      1996-2000, either using the combination of an adjustable Codmann Hakim Valve &
      Miethke Shunt Assistant (35 patients) or a Miethke Dual Switch Valve (150
      patients). The clinical course of each patient has been followed until the end of
      2000. Average follow-up time was 26 months (range 6-60 months). RESULTS: 88% of
      our patients were shunt responders, 70% had a good or excellent outcome.
      Overdrainage occurred in only 4%. It turned out that this complication was not a
      failure of the concept of gravitational shunts, but the result of a wrongly
      estimated intraperitoneal pressure. After shunting the ventricular size was
      reduced only marginally. In 92% of the patients the Evans-Index decreased less
      than 20% after the shunt insertion, but 69% of these patients had a good or
      excellent outcome. The most obvious difference comparing pre- and postoperative
      imaging was a better visibility of the high apical sulci after shunting.
      CONCLUSION: In our series gravitational shunts proved to be effective in
      preventing overdrainage. The 4% negative exceptions are mainly avoidable. There
      was no correlation between outcome and ventricular size reduction, and as a rule
      ventricular size was only marginally reduced.

PMID- 12181685
TI  - Neural activity of the globus pallidus interna and its anatomical relations to
      the optic tract in Parkinson's disease.
AB  - BACKGROUND: To reveal landmarks for placing the globus pallidus interna (GPi)
      target on MR images, visual evoked potentials (VEPs) of the optic tract (OT) and
      neural activities of the GPi were studied retrospectively. METHODS: The dorsal
      and lateral border of the OT were determined by VEPs of the OT, and neural
      activity in the pallidal region was recorded with a semimicro-electrode in 20
      patients. The Unified Parkinson's Disease Rating Scale (UPDRS) was used to assess
      the condition of each patient before and 6 months and 12 months after surgery.
      FINDINGS: The location of trajectories relative to the lateral border of the OT
      were 3 mm medial (-3) in 6, 2 mm medial (-2) in 7, 1 mm medial (-1) in 8, at the
      lateral border (0) in 6, 1 mm lateral (+1) in 5, 2 mm lateral (+2) in 6, and 3 mm
      lateral (+3) in 5. The mean amplitudes along trajectories -3 and -2 mm were
      significantly higher than the others (post-hoc, p<0.01). In dorsoventral
      relations, the amplitudes from 5.1 mm to 6.8 mm of the medial trajectories (-3 to
      0 mm) were significantly higher than others (post-hoc, p<0.01). The lesions
      placed medial to the lateral border of the OT located just above the lateral
      border of the OT on postoperative MR images (n=12) and brought better surgical
      benefits of total motor score, rigidity and bradykinesia than those placed
      lateral to the OT (n=8). INTERPRETATION: Our data indicate that hyperactive cells
      of the GPi are located medial to the lateral border of the OT and at least 5.1 mm
      above its dorsal surface, and this corresponds to the area just above the lateral
      border of the OT on MR images.

PMID- 12181686
TI  - Cranial neuronavigation with direct integration of (11)C methionine positron
      emission tomography (PET) data -- results of a pilot study in 32 surgical cases.
AB  - BACKGROUND: MRI detects small intracranial lesions, but has difficulties in
      differentiating between tumour, gliosis and edema. (11)C methionine-PET may help
      to overcome this problem. For its appropriate intra-operative use, it must be
      integrated into neuronavigation. We present the results of our pilot study with
      this method. METHOD: 32 patients with 34 intracranial lesions detected by MRI
      underwent additional (11)C methionine-PET, because the pathophysiological
      behaviour or the tumour delineation was unclear. All lesions were treated
      surgically. In 25 patients PET data could be integrated directly into cranial
      neuronavigation. FINDINGS: (11)C methionine uptake was observed in 27/34 lesions,
      26 of them were tumours: 14 malignant and 7 benign gliomas, 3 gliomas without
      further histological typing, one Ewing sarcoma and one non-Hodgkin lymphoma. Only
      one (11)C methionine positive lesion was non-tumourous: it was staged as post
      irradiation necrosis in a patient operated on for a malignant glioma. 3/7 (11)C
      methionine negative lesions were classified as gliosis (n=2) and M. Whipple
      (n=1), but 4/7 were tumours: 2 astrocytomas WHO(degrees)II, 1 DNT and one
      astrocytoma WHO(degrees)III. The sensitivity of (11)C methionine-PET was 87%, the
      specificity 75%, the positive predictive value 96% and the negative predictive
      value 43%. In all tumourous cases with positive tracer uptake the borderline area
      of the tumour was better defined by (11)C methionine-PET than by MRI.
      INTERPRETATION: A positive (11)C methionine-PET is highly suspicious of a tumour,
      a negative one does not exclude it. (11)C methionine-PET seems to be more
      sensitive than MRI for differentiating between tumour and edema or gliosis.
      Simultaneous integration MRI and (11)C methionine-PET into cranial
      neuronavigation can facilitate cross total tumour removal in glioma surgery.

PMID- 12181687
TI  - Palliative occipito-cervical stabilization in patients with malignant tumors of
      the occipito-cervical junction and the upper cervical spine.
AB  - BACKGROUND: Occipital-cervical stability may be impaired in patients with primary
      malignant or metastatic tumors of the cranio-cervical junction and the upper
      cervical spine. The purpose of this study was to evaluate occipital-cervical
      fixation with pre-bent titanium-loops and sublaminar wiring in order to achieve a
      rigid and safe stabilisation of the occipito-cervical region in this group of
      patients. METHOD: 20 patients with severe impairment of occipito-cervical
      stability due to primary malignant or metastatic cervical bone involvement were
      included in this study. For palliation of symptoms, resulting from destructive
      instability, a stabilization procedure using Ransford Loops with sublaminar cable
      fixation was used in these patients as a palliative therapeutic concept.
      FINDINGS: Pain which was the major symptom in all patients treated, showed good
      and immediate response to the stabilization procedures. All 20 patients were
      either pain free or had good improvement with less intake of analgesic drugs.
      Signs of spinal cord compression like spasticity and quadraparesis were less
      likely to improve after surgery. However in 3 of 5 patients neurological function
      improved after surgery whereas in 2 patients no improvement was achieved.
      INTERPRETATION: In all patients with impaired occipito-cervical stability due to
      primary malignant or metastatic tumors of the occipito-cervical junction and the
      upper cervical spine, immediate stabilization resulting in an improvement of pain
      was achieved. Occipito-cervical stabilization using contoured Ransford loops is a
      promising palliative therapeutic concept in this group of patients.

PMID- 12181688
TI  - Decompressive craniectomy for the management of patients with refractory
      hypertension: should it be reconsidered?
AB  - INTRODUCTION: The management of refractory post-traumatic cerebral oedema remains
      a frustrating endeavor for the neurosurgeon and the intensivist. Mortality and
      morbidity rates remain high, despite refinements in medical and pharmacological
      means of controlling intracranial hypertension. METHOD AND MATERIAL: In this
      retrospective study we have evaluated the efficacy of decompressive craniectomy
      as a last resort therapy, from the data of nine patients with severe brain injury
      and delayed cerebral oedema (diffuse injury type III), treated between January
      1997 and September 1999. The following parameters were considered: age, Glascow
      Coma Scale, injury severity, intracranial pressure, CT findings, pupil
      reaction/posturing. Follow-up period was over at least 2 years and outcome
      measured on the GOS. RESULTS: Patients have been operated on post-trauma median
      day 3, mean age 26+/-9, GCS 7+/-3.7, mean APACHE II 16+/-6.4, mean ISS 27.8+/
      16.1, mean preoperative ICP 37.7+/-10.0, mean postoperative ICP 18.1+/-16.01.
      Seven patients have been operated by a frontotemporoparietal approach (six of
      them bilateral, one unilateral) and two patients have been operated on by a
      bilateral subtemporal approach. Mortality rates 22%, severe disability 11%, good
      recovery 66%. DISCUSSION: Patients with STBI, developing delayed intracranial
      hypertension caused by diffuse cerebral oedema, definitely benefit from
      craniectomy when current medical treatment has failed. The encouraging results of
      outcome in this and more recent studies, indicate the need for a multi
      institutional randomized prospective study evaluating early indicators of raised
      ICP, timing, efficacy of treatment, operative technique and complications of
      decompressive craniectomy.

PMID- 12181689
TI  - Right hemispheric frontal lesions as a cause for anorexia nervosa report of three
      cases.
AB  - OBJECT: Aetiology and pathogenesis of eating disorders is a matter of
      controversy. In some cases they can occur in association with tumours involving
      the temporal cortex, in temporal lobe epilepsy or in the advanced state of
      degenerative diseases involving temporal structures. We report about three
      patients with right frontal intracerebral lesions, one oligo-astrocytoma and two
      vascular malformations, associated with partial seizures and anorexia nervosa.
      PATIENTS AND METHODS: 3 patients, one female and two men with anorexia nervosa
      and right frontal intracerebral lesions were admitted to our wards due to focal
      seizures or loss of consciousness. They were treated either microsurgically or by
      endovascular embolization after neuro-imaging. In our retrospective analysis of
      the patients' reports and course we investigated the histopathology of the
      lesions, duration of the eating disorder and the clinical outcome. RESULTS: Two
      patients underwent craniotomy with extirpation of the lesion. In one case
      histology revealed an oligo-astrocytoma, in the other haemorrhagic infarction due
      to a venous malformation. The patient with the arteriovenous malformation (AVM)
      was embolized with microparticles. The patients with the oligoastrocytoma and AVM
      totally recovered. They gained weight and stayed seizure free. The patient with
      the infarction remained in a vegetative state. CONCLUSIONS: Right frontal
      intracerebral lesions with their close relationship to the limbic system could be
      causative for eating disorders. We therefore recommend performing a cranial MRI
      in all patients with suspected eating disorders, especially if they occur in
      combination with focal seizures.

PMID- 12181690
TI  - Accumulation of PN1 and PN3 sodium channels in painful human neuroma-evidence
      from immunocytochemistry.
AB  - BACKGROUND: The axolemmal distribution and density of voltage-gated sodium
      channels largely determines the electrical excitability of sprouting neurites.
      Recent evidence suggests that accumulation of sodium channels at injured axonal
      tips may be responsible for ectopic axonal hyperexcitability and the resulting
      abnormal sensory phenomena of pain and paresthesias. For future improvement in
      pain management it is necessary to identify structurally significant generators
      of autorhythmicity. A first step in this regard will be to determine the
      predominant types of sodium channels in injured axons. The opportunity to test
      human specimens from painful and non-painful neuroma is of great value. METHODS:
      We employed immunocytochemical methods to investigate if two types of highly
      specific voltage-gated sodium channel subtypes could be detected in sections of
      human neuroma. FINDINGS: Both subtypes of sodium channels PN1 and PN3 accumulated
      abnormally in human neuromas. The immunoreactive pattern was more pronounced in
      painful neuromas. This is in contrast to previous reports that focused either on
      PN1 or PN3 as main generators of hyperexcitability induced pain. INTERPRETATION:
      Both, PN1 and PN3 seem to be involved in hyperexcitability induced pain. It can
      be expected that a variety of other highly specific voltage gated sodium channel
      subtypes will be detected in regenerating peripheral nerve in the near future,
      which contribute to the development of neuropathic pain states. Thus, in order to
      therapeutically control hyperexcitability induced neuropathic pain, it might be
      worthwhile to develop pharmaceuticals that can selectively block different sodium
      channel subtypes and subunits.A review of the role of sodium channels in
      neuropathic pain is implemented in the discussion.

PMID- 12181691
TI  - Fast in vivo water quantification in rat brain oedema based on T(1) measurement
      at high magnetic field.
AB  - BACKGROUND: In vivo water content determination based on magnetic resonance (MR)
      method is of importance in clinical practice as well as in animal studies to
      follow up the treatment given in order to reduce brain oedema. The methods
      proposed in the literature so far are largely time consuming. The aim of this
      study was to find a fast in vivo water quantification method having real
      advantage for patients suffering from critical conditions. METHOD: Cold injury
      was applied to provoke brain oedema in fourteen rats. T(1) values of both the
      oedematous area and the contralateral normal cortex were determined by two
      independent methods 24 hours after the cold impact. First, from a series of
      images recorded by inversion recovery spin echo (IRSE) sequence and then by
      progressive saturation experiment performed by localised MR spectroscopy using
      stimulated echo acquisition mode (STEAM). To reduce the acquisition time, a two
      element repetition time array was optimised for the STEAM experiment, whereas
      four inversion times were used for T(1) mapping. Both methods were validated
      against gel phantoms with known T(1) values. After the MR measurements the
      animals were sacrificed and the water contents of the regions of interest were
      determined by gravimetric wet-dry method. FINDINGS: The reciprocals of the in
      vivo measured T(1) values were correlated with the reciprocals of the brain water
      contents. STEAM experiment showed stronger correlation (r=0.96) than IRSE
      (r=0.93). In addition, STEAM provided more accurate T(1) values in the phantom
      study. Determination of brain water content based on T1 measurement does work
      also at high magnetic field. Determination of brain water content by Magnetic
      Resonance Spectroscopy is feasible within 2 minutes. INTERPRETATION: Using the
      presented fast method, water content can be determined within a couple of minutes
      in animal experiments as well as in the daily clinical practice.

PMID- 12181692
TI  - Efficacy of methylprednisolone in acute experimental cauda equina injury.
AB  - In this experimental study the efficacy of methylprednisolone was investigated by
      neurophysiological and histopathological evaluation in a rabbit cauda equina
      model where injury was produced with an aneurysm clip (closed pressure 192 gr).
      High dose methylprednisolone (kg/30 mg) was administered by intravenous infusion
      in the 8th, 16th and 24th hours after injury followed by infusion of the same
      dosage every 6 hours for 24 hours. Nerve conduction velocity was measured before
      and early after trauma and 3 weeks after injury. Both neurophysiological and
      histopathological investigations demonstrated the neuroprotective effectiveness
      of methylprednisolone if it was given in the 8th hour after trauma. Although
      recovery was observed its efficacy was less pronounced when it was given in the
      16th and 24th hours.

PMID- 12181693
TI  - Neurocytoma of the thoracic spinal cord.
AB  - Central neurocytoma is an unusual tumour that arises in the supratentorial
      ventricular system of young adults. Similar lesions, termed simply neurocytoma,
      have been described at a variety of locations outside the ventricular system.
      Here, we report the case of a 50-year-old man who presented with pain and a
      rapidly progressive myelopathy due to a neurocytoma of the upper thoracic spinal
      cord. The literature on spinal neurocytoma and its relation to central
      neurocytoma are discussed.

PMID- 12181694
TI  - Cerebellar liponeurocytoma. Case report with considerations on prognosis and
      management.
AB  - BACKGROUND: Cerebellar liponeurocytoma has only recently been recognized as a
      distinct clinicopathological entity. Although the few cases described in
      literature support the relatively benign nature of this lesion, optimum treatment
      strategy and long term behaviour still have to be defined. CLINICAL PRESENTATION:
      This 61-year-old man came under our observation with unspecific signs of
      intracranial hypertension and a symptomathology revealing a probable posterior
      fossa lesion. Imaging studies showed a cerebellar mass lesion with prevalent
      adipose content. INTERVENTION: Gross total tumour removal was performed. The
      pathological examination revealed a lesion composed of medulloblastoma-like cells
      with prominent areas of lipidisation. A review of literature has been made in an
      attempt to investigate on recurrence patterns, importance of the extent of
      removal and the usefulness of radiotherapy. CONCLUSION: The few cases reported in
      literature so far seem to confirm the relatively benign nature of cerebellar
      liponeurocytoma. No radiotherapy was given in our case and the reasons for this
      decision are reported.

PMID- 12181695
TI  - Sudden onset pharyngeal pain associated with dissecting vertebral artery
      aneurysm.
AB  - BACKGROUND AND PURPOSE: We report a case of sudden onset pharyngeal pain due to
      dissection of the vertebral artery. CASE DESCRIPTION: A 65-year-old patient
      presented with sudden onset of unilateral pharyngeal pain, which was first,
      diagnosed as idiopathic glossopharyngeal neuralgia. Magnetic resonance image and
      cerebral angiography revealed a dissecting vertebral artery aneurysm. The
      anatomical site of the aneurysm may explain this complication. CONCLUSIONS:
      Sudden onset of pharyngeal pain, although rare, should be considered as a
      complication of dissection of the vertebral artery even though there are no other
      general or neurological symptoms.

PMID- 12181696
TI  - Unexpected delayed rupture of the vertebral-posterior inferior cerebellar artery
      aneurysms following closed head injury.
AB  - Subarachnoid haemorrhage secondary to closed head injury is rarely associated
      with traumatic aneurysms of the posterior circulation. We report two cases of
      ruptured vertebral-posterior inferior cerebellar artery (VA-PICA) pseudoaneurysms
      following closed head injuries. In each case, there was no associated penetrating
      injury or skull fracture. The first patient was kicked followed by disturbed
      consciousness. The computerized tomography (CT) scan on admission and cerebral
      angiography on the 11th day after the trauma revealed a massive subarachnoid
      haemorrhage (SAH) with pan-ventricular haemorrhage and an aneurysm of the right
      PICA near its origin. Further ruptures occurred on the 12th, 15th, and 66th day,
      and he died on the 69th day. The second patient complained of persistent headache
      and nausea following a fight on the previous day. A CT scan and angiography on
      the 1st day after the trauma showed posterior fossa SAH with fourth ventricular
      blood and a tiny protrusion of the left VA-PICA. On the 14th day, repeated
      angiography revealed a remarkable growth of the aneurysm, followed by the second
      rupture. The repair of the VA-PICA junction was urgently performed with
      successful exclusion of the aneurysm. To our knowledge, only eight cases of
      traumatic aneurysms located at the VA or the PICA near its origin have been
      reported. When intraventricular blood is found with massive subarachnoid blood or
      with posterior fossa SAH, this ominous complication should be considered.
      Traumatic VA-PICA pseudoaneurysms are curable by refined microsurgical
      techniques, if diagnosed in time.

PMID- 12181697
TI  - Cystic germinoma arising from the right temporal lobe.

PMID- 12181698
TI  - The pathophysiology of syringomyelia - historical overview and current concept.
AB  - Various ideas and hypotheses have been brought forward to explain the development
      of syringomyelia in the past two centuries. None of them offers a sufficient
      basis to serve as a concept for the treatment of all affected patients. Apart
      from a discussion of the different hypotheses this paper proposes a new
      pathophysiological concept based on clinical, experimental and literature
      studies. Syringomyelia is understood as a state of chronic interstitial edema of
      the spinal cord due to accumulation of extracellular fluid (ECF). This
      accumulation is caused by a cascade of events starting with obstruction of
      cerebrospinal fluid (CSF) flow and/or spinal cord tethering which ultimately
      alter ECF flow and increase ECF volume. Treatment should be targeted against the
      pathological process which causes CSF flow obstruction and cord tethering to
      inhibit this pathophysiological process at a decisive point.

PMID- 12181699
TI  - The effects of 10 degrees reverse trendelenburg position on ICP and CPP in prone
      positioned patients subjected to craniotomy for occipital or cerebellar tumours.
AB  - BACKGROUND: Control of ICP-hypertension is of utmost importance during
      craniotomy. The effects of reverse Trendelenburg position (RTP) upon ICP and CPP
      have recently been studied in supine positioned patients. METHOD: In this study
      we investigated changes in intracranial pressure (ICP), mean arterial blood
      pressure (MABP), CPP and jugular bulb pressure (JBP) before and one minute after
      10( degrees ) RTP in 26 prone positioned patients with either occipital (n=12) or
      cerebellar tumours (n=14). ICP was measured by a subdural approach after removal
      of the bone flap. Tension of the dura was estimated by the surgeons by digital
      palpation before and after change in position. FINDINGS: In patients with
      occipital tumours ICP decreased from 21.0 to 15.6 mm Hg (p<0.05). MABP decreased
      from 87.9 to 83.3 mm Hg (p<0.05), JBP decreased from 14.3 to 7.7 mm Hg (P<0.05),
      while CPP was unchanged. In patients with cerebellar tumours ICP decreased from
      18.3 to 14.2 mm Hg (p<0.05). MABP decreased from 93,8 to 90.5 mm Hg (p<0.05), JBP
      decreased from 12.1 to 5.0 mm Hg (P<0.05), while CPP was unchanged. There were no
      significant differences between the two groups with regard to changes in ICP,
      MABP, CPP and JBP. The change in ICP was accompanied by a significant decrease in
      dural tension (p<0.05). INTERPRETATION: In prone positioned patients 10 degrees
      RTP significantly reduces ICP, JPB and MABP within one minute, while CPP is
      unchanged.

PMID- 12181700
TI  - Radiosurgery of residual and recurrent vestibular schwannomas.
AB  - Radiosurgery is either a primary or an adjunctive management approach used to
      treat patients with vestibular schwannomas. We sought to determine outcomes
      measuring the potential benefits against the neurological risks in patients who
      underwent radiosurgery after previous microsurgical subtotal resection or
      recurrence of the tumour after total resection. Gamma Knife radiosurgery was
      applied as an adjunctive treatment modality for 86 patients with vestibular
      schwannomas from April 1992 to August 2001. We evaluated the results of 50
      patients who had a follow-up of at least 3.5 years (median 75 months, range 42
      114 months). In 16 patients a recurrence of disease was observed after previous
      total resection. The median treatment volume was 3.4 ccm with a median dose to
      the tumour margin of 13 Gy. Tumour control rate was 96%. Two tumours progressed
      after adjunctive radiosurgery. Useful hearing (Gardner-Robertson II) (4 patients
      (8%)) and residual hearing (Gardner-Roberson III) (10 patients (20%)) remained
      unchanged in all patients, who presented with it before radiosurgery,
      respectively. Clinical neurological improvement was observed in 24 patients
      (46%). Adverse effects comprised transient neurological symptoms and signs
      (incomplete facial palsy, House-Brackman II/III) in five cases (recovered
      completely), mild trigeminal neuropathy in four cases, and morphological changes
      displaying rapid enlargement of a pre-existing macrocyst in one patient and
      tumour growth in another one. No permanent new cranial nerve deficit was
      observed. Radiosurgery appears to be an effective adjunctive method for growth
      control of vestibular schwannomas and is associated with both a low mortality
      rate and a good quality of life. Accordingly, radiosurgery is a rewarding
      therapeutic approach for the preservation of cranial nerve function in the
      management of patients with vestibular schwannoma in whom prior microsurgical
      resection failed.

PMID- 12181701
TI  - Local changes in cerebral energy metabolism due to brain retraction during
      routine neurosurgical procedures.
AB  - PATIENTS AND INTERVENTIONS: Tissue damage caused by brain retraction was
      evaluated utilizing intracerebral microdialysis in six patients operated on
      subfrontally for pituitary adenoma. The microdialysis probes (membrane length 10
      mm, cut-off 20 kDalton) were placed in cerebral cortex beneath the brain
      retractor and perfused with Ringer solution at 0.3 microl/min. The microdialysis
      vials were changed at intervals of 30 minutes and analysed for glucose, pyruvate,
      lactate, glutamate and glycerol. RESULTS: During brain retraction regional
      intracerebral glucose was within normal range in cortical tissue and the levels
      of lactate, glutamate, and glycerol as well as the lactate/pyruvate ratio were
      considerably above normal range. CONCLUSION: The biochemical analysis shows a
      pronounced incomplete cerebral ischemia due to brain retraction. The increases in
      glutamate and glycerol indicate tissue damage and degradation of cell membranes.
      Intracerebral microdialysis may be a valuable tool in the development of optimal
      techniques for brain retraction during neurosurgical procedures.

PMID- 12181702
TI  - Microsurgical anterior cervical foraminotomy (uncoforaminotomy) for unilateral
      radiculopathy: clinical results of a new technique.
AB  - BACKGROUND: The authors report the clinical application of a new microsurgical
      technique. The cervical anterior foraminotomy (uncoforaminotomy), which is used
      for the surgical treatment of unilateral cervical radiculopathy secondary to
      posterolateral disc herniations or spondylotic foraminal stenoses. METHOD:
      Between June 2000 and May 2001, 34 patients (16 men and 18 women with a mean age
      of 43.8 years, range 29 to 80 years) underwent anterior cervical foraminotomy
      (uncoforaminotomy) for the treatment of cervical radiculopathy at one or two
      adjacent levels in the Neurosurgical Department of the University of Vienna. This
      surgical technique was devised to accomplish direct anterior decompression of the
      affected nerve root by removing an offending posterolateral sponylotic spur or
      disc fragment. The nerve root is decompressed from its origin in the spinal cord
      to the point were it passes behind the vertebral artery laterally. The
      intervertebral disc of the affected level is maintained in its form and function.
      Thus, the functioning motion segment is preserved and fusion related sequelae,
      including graft related complications, graft site complications and the adjacent
      level disease, are avoided. Prior to its clinical application, anatomical
      features of the anterior cervical spine were reviewed, and an anatomical
      morphometric analysis and work-up of the technique was performed in 4 cervical
      specimens. FINDINGS: The follow-up period varied from two to 17 months with a
      mean of 8.2 months. The large majority (97%) of patients were pleased with the
      results of their operation. The relief of neck pain and redicular pain in the
      affected dermatome was immediate in all patients. Motor-weakness and sensory
      deficit improved dramatically immediately postoperatively, and improved to
      normalisation in the majority of patients within 3 to 6 months. Two of the
      patients sustained an incomplete transient recurrent laryngeal nerve palsy, which
      fully resolved within two to 4 weeks. One of the patients had a repeat herniation
      on the second postoperative day, but recovered completely after re-operation and
      continued to do well at the 6-month follow-up. No permanent surgery related
      morbidity or associated complications were encountered. INTERPRETATION: The
      results indicate that this new microsurgical technique is an attractive treatment
      option for adequate anterior decompression of the cervical nerve root via a
      minimized approach. It was associated with excellent clinical outcome and a less
      painful postoperative course, allowing patients an almost immediate return to
      unrestricted full activity.

PMID- 12181703
TI  - Double noncontiguous cervical spinal injuries.
AB  - BACKGROUND: Double noncontiguous spinal injuries in the same patient, the first
      at the cervical level and the second at the thoracic or thoracolumbar level are
      not uncommon. On the other hand the incidence of double noncontiguous cervical
      injuries in low and these injuries imply complex mechanisms. This study
      investigates the cases of double noncontiguous cervical lesions in 342 cases of
      acute cervical injuries. METHOD: An analysis of 342 patients with cervical
      injuries found 67 multiple cervical injuries and only 11 cases of double
      noncontiguous cervical lesions. FINDINGS AND INTERPRETATION: Double noncontiguous
      cervical injuries have a frequency of 3.2% in this study and in three cases there
      were pre-existing benign cervical lesions. A possible spinal biomechanical
      behaviour during injury can be that the first lesion appears because of the
      traumatic impact and there is a uniform transmission of the remaining traumatic
      strain all along the spine. It seems that the propagated force finds a spinal
      zone where the spinal resistance is diminished and the second spinal lesion can
      occur. Spinal vulnerability for the second lesion in the same trauma can be
      caused by a pre-existing benign spinal lesion or by a biomechanical discontinuity
      because of a particular posture at the traumatic moment. The second lesion in
      double noncontiguous cervical lesions can appear through a single great impact in
      pre-existing lesions, double impacts at the same time with injuries at two
      cervical levels or repeated cervical impacts in very quick succession in the same
      trauma.

PMID- 12181704
TI  - Effects of iso- and hypervolemic hemodilution on regional cerebral blood flow and
      oxygen delivery for patients with vasospasm after aneurysmal subarachnoid
      hemorrhage.
AB  - BACKGROUND: Arterial vasospasm after subarachnoid hemorrhage may cause cerebral
      ischemia. Treatment with hemodilution, reducing blood viscosity, and
      hypervolemia, increasing cardiac performance and distending the vasospastic
      artery, are clinically established methods to improve blood flow through the
      vasospastic arterial bed. METHOD: Eight patients with transcranial Doppler
      verified vasospasm after subarachnoid hemorrhage were investigated with global
      (two-dimensional (133)Xenon) and regional (three-dimensional (99 m)Tc-HMPAO)
      cerebral blood flow (CBF) measurements, before and after 1/iso- and
      2/hypervolemic hemodilution. Hematocrit was reduced to 0.28 from 0.36.
      Hypervolemia was achieved by increasing blood volume by 1100 ml. FINDINGS:
      Isovolemic hemodilution increased global cerebral blood flow from 52.25+/-10.12
      to 58.56+/-11.73 ml * 100 g(-1) * min(-1) (p<0.05), but after hypervolemic
      hemodilution CBF returned to 51.38+/-11.34 ml * 100 g(-1) * min(-1). Global
      cerebral delivery rate of oxygen (CDRO(2)) decreased from 7.94+/-1.92 to 6.98+/
      1.66 ml * 100 g(-1) * min(-1) (p<0.001) during isovolemic hemodilution and
      remained reduced, 6.77+/-1.60 ml * 100 g(-1) * min(-1) (p<0.001), after the
      hypervolemic hemodilution. As a test of the hemodilution effect on regional
      CDRO(2) an ischemic threshold was defined as the maximal amount of oxygen
      transported by a CBF of 10 ml * 100 g(-1) * min(-1) at a Hb 140 g/l which
      corresponds to a CDRO(2) of 1.83 ml * 100 g(-1) * min(-1). The brain volume with
      a CDRO(2) exceeding the ichemic threshold was 1300+/-236 ml before intervention.
      After isovolemic hemodilution the non-ischemic brain volume was reduced to 1206+/
      341 (p<0,003). After hypervolemic hemodilution the non-ischemic brain volume
      remained reduced at 1228+/-347 ml (p<0.05). INTERPRETATION: The present study of
      controlled isovolemic hemodilution demonstrated increased global CBF, but there
      was a pronounced reduction in oxygen delivery capacity. Both CBF and CDRO(2)
      remained decreased during further hypervolemic hemodilution. We conclude that
      hemodilution to hematocrit 0.28 is not beneficial for patients with cerebral
      vasospasm after SAH.

PMID- 12181705
TI  - Multi-slice 3D-CTA - an improvement over single slice helical CTA for cerebral
      aneurysms.
AB  - BACKGROUND AND OBJECTIVE: The aim of this study was to demonstrate the utility of
      volume rendered multi-slice helical three-dimensional CT angiography in patients
      with cerebral aneurysm when compared with single slice CT angiography and formal
      digital subtraction angiography. METHODS: A prototype Toshiba Aquilon multi-slice
      CT scanner was employed with the following scan conditions: voltage 135 kV;
      current 300 mA; slice thickness 0.8 mm; scan speed 0.75 sec/cycle; couch speed 1
      mm/sec; range 50 mm from foramen magnum; scan pitch 3; three dimensional images
      were reconstructed using multiple image projections and integral volume rendering
      algorithms on a Xlink/Xtension workstation. 80 cases of multi-slice CTA for
      cerebral aneurysm carried out at Fujita University from January 1999 to January
      2001 were reviewed. RESULTS: The advantages of multi-slice imaging are
      illustrated with representative cases of cerebral aneurysm - good demonstration
      of three dimensional anatomy, appreciation of perforators down to 1 mm in size,
      delineation of the vessels around the aneurysm complex, relationship between the
      aneurysm and skull base, information on calcification, thrombus and blebs in the
      wall and eleven routine views for perusal. CONCLUSION: Multi-slice CTA is a
      significant improvement over single slice CTA for cerebral aneurysms. It is our
      experience the superior and precise images produced by multi-slice technology
      displays anatomical information not readily available from standard DSA.
      Multislice 3D-CTA is relatively non-invasive and provides better and adequate
      detail for surgical planning. The basis of multi-slice CT angiography is
      described. Multi slice CTA is changing the way cerebral aneurysms are being
      managed nowadays. New advances in the technology of multi-slice CTA resulting in
      increased image resolution are outlined.

PMID- 12181706
TI  - Diffuse arachnoidal enhancement of a well differentiated choroid plexus
      papilloma.
AB  - INTRODUCTION: The case of a 38-year old man with a histologically benign choroid
      plexus papilloma arising within the fourth ventricle with en plaque growth around
      the brain stem and medulla is described in detail. Up to this point this
      particular growth pattern has not been published and is a rare presentation for
      this tumour. CLINICAL PRESENTATION: The patient presented with a 1.5 year history
      of headache, nausea, and vomiting in the morning. Additional symptoms like
      blurred vision and gait ataxia lead to hospital admission. MRI demonstrated a
      homogeneously contrast-enhancing tumour completely filling the fourth ventricle
      and subsequent obstructive hydrocephalus. In addition Gd enhancement encasing the
      brain stem, the lower aspect of the medulla and the conus medullaris was seen
      suggesting a disseminated ependymoma or medulloblastoma. INTERVENTION: An
      extensive resection of the tumour in the fourth ventricle and CP angle was
      performed. Infiltrative growth into the structures of the left CP angle and into
      the rhomboid fossa hampered complete removal. Surprisingly histological
      examination revealed a well-differentiated papillary choroid plexus papilloma
      without signs of anaplasia. On follow up imaging the Gd enhancement encasing the
      pons vanished completely. A growing cyst adjacent to a small tumour residuum left
      behind on the floor of the fourth ventricle led to re-operation after 8 months
      with complete removal. DISCUSSION: This case presents several biological,
      neuroradiological and surgical aspects which make it noteworthy and we hope that
      the informations provided add to the understanding of these tumours, expand the
      differential diagnostic thinking of lesions which present with diffuse arachnoid
      Gd enhancement upon first presentation.

PMID- 12181707
TI  - Simultaneous dissection of intra- and extracranial vertebral artery. Report of
      two cases and review of literature.
AB  - Two patients who developed subarachnoid haemorrhage are presented. The first
      patient was a 41-year-old woman whose angiograms showed right extracranial
      vertebral artery (VA) dissection starting at the C2 level extending to the
      intracranial VA near the VA union. Proximal occlusion of the right VA by the
      endovascular approach was performed. The second patient was a 57-year-old man
      whose angiograms showed the left intracranial VA dissection distal to the
      posterior inferior cerebellar artery and an extracranial aneurysmal dilatation of
      the left VA at the C1 level and extracranial VA dissection in the V3 portion of
      the right VA. Left intracranial VA dissection was surgically trapped, and the
      remaining lesions were conservatively treated. Simultaneous dissection of the
      intracranial and extracranial portions of the VA is rare. Such lesions usually
      cause brain ischaemia, but may cause intracranial subarachnoid haemorrhage.

PMID- 12181708
TI  - Intracranial extraskeletal myxoid chondrosarcoma: case report and review of the
      literature.
AB  - BACKGROUND: We describe a patient with an intracranial extra skeletal myxoid
      chondrosarcoma (EMC), an unusual neoplasm of the deep soft tissues of the
      extremities. Very rarely are they localised as an intracranial lesion, and we
      believe it is very important to accurately distinguish EMC from other
      intracranial tumours such as classical or "skeletal" chondrosarcomas, mesenchymal
      chondrosarcoma, enchondroma, and myxoid tumours (chordoma, and chondromyxoid
      fibroma) in order to determine their prognostic implications. Furthermore, this
      case presents with the second local recurrence, higher-grade cellular areas, such
      an event has never been reported in intracranial cases. METHOD: A 17 year-old
      female presented with tonic and clonic seizures, episodic left hemiplegia and
      intense right-sided headaches. Computed tomography and magnetic resonance of the
      skull showed a right fronto-parietal cortical lesion. Complete surgical excision
      of the lesion through a right parieto-temporal craniotomy was performed. The
      tumoral lesion recurred locally twice (16 and 19 months after the initial surgery
      respectively). FINDINGS: First and second surgical specimens where diagnosed as
      extra skeletal myxoid chondrosarcoma. Microscopically, the third specimen (second
      local recurrence) showed abrupt transition from areas of conventional myxoid
      chondrosarcoma to high-grade cellular areas with fusiform features.
      INTERPRETATION: Extra skeletal myxoid chondrosarcoma is very rarely described as
      an intracranial lesion. Reference on this topic is very confusing as there is no
      clear-cut distinction between skeletal chondrosarcomas with prominent myxoid
      matrix and extra skeletal myxoid chondrosarcoma which is a definite entity first
      defined by Enzinger and Shiraki in 1972 in deep soft tissues of the extremities.
      We review the cases reported in the literature with the diagnosis of myxoid
      chondrosarcoma either of extra skeletal origin or with skeletal attachment, and
      analyse their clinic and pathological features.

PMID- 12181709
TI  - Secondary syringomyelia disappearing after removal of tentorial meningioma.

PMID- 12181711
TI  - Intra- and parasellar manifestation of an Ewing's sarcoma before detection of the
      primary tumour.

PMID- 12181710
TI  - Beare-Stevenson cutis gyrata syndrome with Chiari malformation.

PMID- 12181712
TI  - Bilateral cortical blindness associated with cerebral angiitis.

PMID- 12181714
TI  - Epidermal growth factor receptor and transformation.
AB  - The action of transforming growth factor peptides is mediated by distinct
      membrane receptors, which in turn activate a postreceptor signaling mechanism,
      eventually resulting in a mitogenic response. Such a signaling pathway may be
      modified by oncogene expression at the receptor or postreceptor levels, as well
      as by alterations in the levels of expression of the growth factor itself. One of
      the most extensively studied group of receptors is the type I epidermal growth
      factor receptor family. Activation of this receptor triggers the induction of
      receptor dimerization, which enables cross-phosphorylation to occur between two
      receptor molecules. This dimerization model provides a universal mechanism to
      activate the type I receptor family for growth factors and subsequent
      transformation.

PMID- 12181715
TI  - Enteral nutrition in surgical patients.
AB  - PURPOSE: Malnutrition is well-recognized as a potential cause of increased
      morbidity and mortality in surgical patients; however, enteral and parenteral
      nutritional support given pre- and postoperatively have been shown to decrease
      these rates. We conducted a prospective study to assess the short-term efficacy
      of oral dietary supplementation in malnourished patients undergoing major
      abdominal surgery. METHODS: Sixty patients undergoing major abdominal surgery
      were divided according to nutritional risk index into borderline (BM), moderately
      (MM), and severely (SM) malnourished categories. The patients in each category
      were randomly divided into a treatment group (TG) and a control group (CG). TG
      patients were given an oral sip feed containing 500 kcal of energy and 16.66 g of
      protein in addition to their daily oral intake. The differences in nutritional
      intake, in terms of energy and protein, and the changes in nutritional status, as
      assessed by anthropometric, biochemical, and hematological values, complication
      rates, and duration of stay were compared. RESULTS: The supplemented feeds were
      well tolerated and the total caloric and protein intake in the TG was
      significantly higher than in the CG, at 1798 vs 1182 kcal ( P < 0.01), protein
      55.71 vs 39.48 g ( P < 0.01), respectively. Weight loss in the SM patients was
      significantly less in the TG than in the CG, at 2.15 vs 4.6 kg ( P < 0.001),
      respectively. Complications developed in 7 of the 30 TG patients and in 10 of the
      30 CG patients, with maximum reduction seen in the SM category (7 in the CG vs 4
      in the TG). CONCLUSIONS: Patients with severe malnutrition are likely to develop
      large energy deficits postoperatively, resulting in loss of body mass and a
      higher incidence of infective complications. Oral nutritional supplements are
      well tolerated by these patients, and help to improve their energy and routine
      intake and reduce the risk of complications.

PMID- 12181716
TI  - Postoperative hyperbilirubinemia after surgery for gastrointestinal perforation.
AB  - PURPOSE: The aim of this study was to evaluate the risk factors and outcome of
      patients with hyperbilirubinemia after surgery for generalized peritonitis.
      METHODS: We retrospectively analyzed data from 229 patients with generalized
      peritonitis caused by gastrointestinal (GI) perforations. RESULTS: Postoperative
      hyperbilirubinemia defined as a value of > or =5 mg/dl, within 1 month, developed
      in 39 patients. Postoperative hyperbilirubinemia was related to age ( P =
      0.0102), poor nutritional status ( P = 0.0388), decreased base excess ( P =
      0.0037), delay until surgery ( P = 0.0276), preoperative serum bilirubin ( P =
      0.0321) and postoperative persistent infection ( P < 0.0001). Higher mortality
      was seen in patients with hyperbilirubinemia (59%) than in those without
      hyperbilirubinemia (4%). The patients with hyperbilirubinemia who survived had
      decreased serum bilirubin levels after 3-5 postoperative days whereas a
      continuous increase was seen in the patients who ultimately died. Preoperative
      shock ( P = 0.0003), a decreased preoperative platelet count ( P = 0.0152),
      postoperative infection ( P = 0.0050), and postoperative hyperbilirubinemia ( P <
      0.0001) were risk factors for overall mortality. CONCLUSION: These results
      indicate that postoperative hyperbilirubinemia in patients with GI perforation is
      related to persistent postoperative infection and associated with poor prognosis.

PMID- 12181717
TI  - Hemodynamic changes during gaseous and gasless laparoscopic cholecystectomy.
AB  - PURPOSE: The main disadvantage of gaseous laparoscopic surgery is the need for
      CO(2) insufflation and the elevation of intra-abdominal pressure. Gasless
      laparoscopic surgery is an alternative to gaseous laparoscopic surgery, which
      avoids the hazardous effects of pneumoperitoneum. This study was conducted to
      investigate the hemodynamic effects of pneumoperitoneum and to compare gasless
      and gaseous laparoscopic cholecystectomy on a hemodynamic basis. METHODS: The
      gasless laparoscopic procedure uses an electromechanical retractor system to lift
      the abdominal wall. We performed 20 gaseous and 11 gasless laparoscopic
      cholecystectomies in a collective total of 31 patients with symptomatic
      gallstones. The mean arterial pressure, heart rate, end diastolic index, systemic
      vascular resistance index, cardiac index (CI), ejection fraction (EF), and stroke
      index (SI) values were monitored noninvasively by thoracic electrical
      bioimpedance. RESULTS: In the gaseous group, statistically significant changes
      were detected in CI, EF, and SI values after insufflation as compared to the
      values before pneumoperitoneum. In the gasless group, only minimal changes were
      detected in the SI values, which were not significant. CONCLUSION: Gasless
      laparoscopy has little effect on the hemodynamic parameters of patients and
      provides an alternative to the gaseous technique in selected cases.

PMID- 12181719
TI  - Gut glutamine metabolism at different stages of sepsis in rats.
AB  - PURPOSE: To investigate gut glutamine metabolism and determine the effects of
      glutamine supplementation in different stages of sepsis in a rat model. METHODS:
      Sepsis was induced by cecal ligation and puncture (CLP), and control rats
      underwent a sham operation. In the first experiment, a continuous infusion of
      normal saline was started at the end of the operation. Intestinal blood flow,
      glutamine concentrations of the abdominal aorta and superior mesenteric vein
      (SMV) were measured, and gut glutamine extraction and flux were calculated 5 h
      after the sham operation, and 5 and 20 h after CLP, being groups Ia ( n = 9), Ib
      ( n = 8), and Ic ( n = 8), respectively. In the second experiment, animals
      received a continuous infusion of alanyl-glutamine instead of normal saline and
      were divided into groups IIa ( n = 8), IIb ( n = 8), and IIc ( n = 6). The same
      parameters were measured in each group and compared with those of the
      corresponding group in the first experiment. RESULTS: In the first experiment, no
      significant difference in SMV blood flow was seen among the groups. The arterial
      glutamine concentration was increased in group Ic ( P < 0.05) compared with that
      in groups Ia and Ib. Gut glutamine extraction was significantly increased in
      group Ib ( P < 0.01) and significantly decreased in group Ic ( P < 0.05) compared
      with that in group Ia. In the second experiment, gut glutamine flux was
      significantly increased in group Ilb ( P < 0.01) compared with that in group Ib,
      but the increase did not reach statistical significance between groups Ia and IIa
      or between groups Ic and IIc. CONCLUSION: These results indicate that intestinal
      glutamine uptake is increased and glutamine utilization is enhanced by glutamine
      supplementation in early sepsis.

PMID- 12181718
TI  - Expression of somatostatin receptor and effects of somatostatin analog on
      pancreatic endocrine tumors.
AB  - PURPOSE: Somatostatin analogs have been administered to patients with pancreatic
      endocrine tumors in an attempt to inhibit hormone hypersecretion and prevent
      tumor growth. It is speculated that their efficacy is correlated with the
      expression of specific subtypes of somatostatin receptors. The aim of this study
      was to immunohistochemically evaluate the expression of somatostatin receptor
      subtypes in human pancreatic endocrine tumors, and to determine whether the
      expression of these subtypes is correlated with the effectiveness of the
      somatostatin analogs. METHODS: Somatostatin receptor subtypes 1, 2, and 3 (sst 1,
      2, and 3) were immunohistochemically investigated in seven pancreatic endocrine
      tumors: four insulinomas, one VIPoma, and two nonfunctioning tumors associated
      with multiple endocrine neoplasia type I, using paraffin sections. Three of the
      four patients with insulinoma were given an octreotide injection. RESULTS: Cells
      were homogeneously stained in the tumor region. More than 85% of the specimens
      expressed sst 1, 2, and 3. There was no difference among the immunohistochemical
      stainings of somatostatin receptor subtypes according to most tumor
      characteristics; however, the expression of sst 2 was extremely positive, and the
      expression of sst 3 was moderately positive in the specimen from a patient in
      whom the octreotide injection had proven very effective. CONCLUSION: These
      findings indicate that the efficacy of octreotide may be correlated with the
      density of sst 2 and 3 in an immunohistological study using paraffin sections.

PMID- 12181720
TI  - Cellular localization of tumor necrosis factor-alpha mRNA and interleukin-6 mRNA
      in the rat liver after hemorrhagic shock.
AB  - PURPOSE: Our previous studies showed that tumor necrosis factor (TNF)-alpha and
      interleukin (IL)-6 are induced after hemorrhagic shock and that their induction
      is attenuated by hyperbaric oxygen treatment. In this study, we tried to identify
      the cell types in the liver that are responsible for the increase in TNF-alpha
      mRNA and IL-6 mRNA after hemorrhage using in situ reverse transcription
      polymerase chain reaction (in situ RT-PCR). METHODS: Chronically cannulated rats
      were subjected to hemorrhage, maintaining a mean arterial blood pressure of 40
      mmHg for 1 h. They were resuscitated with the collected blood and saline, and the
      livers were removed at designated times, then fixed and frozen. RESULTS: Standard
      in situ hybridization could not detect the mRNAs of TNF-alpha and IL-6 in the
      livers; however, in situ RT-PCR detected TNF-alpha mRNA and IL-6 mRNA mainly in
      the vascular endothelial cells and perivascular nonparenchymal cells of the bled
      rats. Sinusoidal cells were positive for TNF-alpha mRNA, but negative for IL-6
      mRNA. No signal was found in normal rats, or when the experimental protocol was
      modified to: omit the RT step; precede the RT step with RNA digestion; or use an
      irrelevant probe. CONCLUSION: These results show that vascular endothelial cells
      and perivascular nonparenchymal cells are activated after massive hemorrhage to
      produce inflammatory cytokines.

PMID- 12181721
TI  - Vasoactive peptides in a pulmonary embolism model.
AB  - PURPOSE: To investigate changes in atrial natriuretic peptide (ANP) and
      angiotensin II (AT-II) levels in a canine model of pulmonary embolism (PE),
      created by embolizing the left posterior pulmonary artery with gelatin powder.
      METHODS: Pulmonary arterial pressure (PAP) was measured before, immediately
      after, and 1 day after pulmonary artery embolization. Plasma ANP and AT-II levels
      were measured by radioimmunoassay (RIA) before and 1, 3, 7, 14, 21, and 28 days
      after embolization. ANP and AT-II levels were also measured by RIA in both
      embolized and nonembolized lung tissue 28 days after embolization. RESULTS: No
      changes in plasma ANP or AT-II were seen within 28 days after embolization.
      Although the ANP level in the nonembolized lung tissue was significantly
      increased, the level in the embolized lung tissue was significantly decreased
      compared with that of sham-operated control lung tissue. The AT-II level in the
      nonembolized lung tissue was significantly decreased compared with that of the
      control lung tissue, but the level in the embolized lung tissue did not change.
      CONCLUSION: Both ANP and AT-II in the nonembolized lung tissue reacted to
      compensate for vasoconstriction caused by the PE in this model.

PMID- 12181722
TI  - Live donor partial liver harvest for canine liver transplantation: development of
      an innovative technique for surgical training and research.
AB  - PURPOSE: Most models of canine segmental liver transplantation use about 40% of
      the total liver volume including the left lateral and medial segments, an
      approach which is associated with some shortcomings. First, during live donor
      harvest, a necrotic segment requiring further resection is unavoidable after
      removal of the donor segments; and second, to harvest the left lobe, two
      dissection planes must be used. This creates some technical bias and limitations
      in designing a canine research model. Herein, we report a new technique of
      harvesting up to 70% of the liver in dogs. METHODS: The right medial and quadrate
      segments, the left lobe, and the papillary process of the caudate lobe were
      resected and harvested for transplantation. We divided the middle hepatic vein to
      enable a single parenchymal dissection between the right medial and lateral
      segments and no perfusion defect was seen. Using this technique, we performed
      orthotopic autoauxiliary transplantation ( n = 6) and orthotopic alloauxiliary
      transplantation ( n = 5) in dogs. RESULTS: All dogs transplanted with an
      autograft were alive at the completion of surgery. All donor dogs providing 70%
      of the liver volume for allografts were alive 1 week after surgery, and all five
      allograft recipient dogs were alive 48 h after surgery, at which point they were
      killed. CONCLUSIONS: This novel experimental technique of partial living donor
      liver transplantation using about 70% of the liver allows for easier harvest and
      effective live donor partial liver transplantation. Moreover, the fact that
      division of the liver parenchyme can be done without leaving a necrotic segment
      shows the possibilities for various research models of ischemic-reperfusion
      injury. This technique allows us to divide the liver in situ, then subject the
      right segment of the liver to various insults or remedies for comparison.

PMID- 12181723
TI  - Primary leiomyosarcoma of the breast: report of a case.
AB  - We describe herein a case of primary leiomyosarcoma of the breast in a 59-year
      old woman. Preoperative clinical examination and cytology findings indicated a
      benign breast tumor, but intraoperative histopathological examination of the
      tumor revealed malignant spindle cells, and a modified radical mastectomy was
      performed. Immunohistochemical analysis subsequently confirmed a diagnosis of
      leiomyosarcoma. Primary leiomyosarcoma of the breast is extremely rare and
      difficult to diagnose before surgery because of the need for mitotic figures and
      immunohistochemical staining to confirm the diagnosis. When pre- and
      intraoperative examinations indicate the possibility of a leiomyosarcoma, an
      extended excision with sufficient margins should be performed to remove all of
      the affected tissue. A review of the literature on this unusual tumor of the
      breast is presented.

PMID- 12181724
TI  - Severe stenosis of the true lumen in the abdominal aorta after an ascending aorta
      reconstruction for an acute type a dissection: report of a case.
AB  - We encountered a case of severe symptomatic stenosis of the abdominal aorta after
      a surgical repair of an ascending aortic dissection. A 75-year-old woman
      underwent a reconstruction of the ascending aorta to treat a Stanford type A
      acute aortic dissection and cardiac tamponade. Eight hours postoperatively, the
      patient was anuric. An abdominal computed tomography scan revealed severe
      stenosis of the true lumen of the suprarenal abdominal aorta due to a dilatation
      of the false lumen. The patient's ischemic symptoms progressed to include a
      weakening femoral pulse and, as a result, an emergency right axillofemoral artery
      bypass was performed. We hypothesize that the stenosis of the true lumen of the
      abdominal aorta was secondary to the mechanical obstruction due to a false lumen,
      which already existed because of the thoracic dissection, and its size increased
      postoperatively as a consequence of uncontrolled postoperative hypertension.

PMID- 12181725
TI  - Late embolization of an unfractured port catheter into the heart: report of a
      case.
AB  - This case report describes the embolization of an unfractured venous port
      catheter, 18 months after its implantation into the heart. To our knowledge, this
      complication has never been documented before. A 33-year-old woman underwent
      placement of a totally implantable venous access port for chemotherapy to treat
      advanced gastric cancer. The catheter tip was repositioned by a transfemoral
      sling after dislocation into the right jugular vein 2 months before embolization.
      After embolization into the heart, the catheter was successfully removed by a
      percutaneous femoral vein approach using a dormia basket. As totally implantable
      venous access ports become used more frequently, problems associated with their
      extended use will be encountered.

PMID- 12181726
TI  - Gastrectomy in combination with a distal splenorenal shunt in a patient with
      gastric cancer and portal hypertension: report of a case.
AB  - We describe the case of a patient with gastric cancer complicated by portal
      hypertension due to liver cirrhosis. Endoscopy showed esophageal varices in the
      lower third of the esophagus and a superficially depressed lesion in the middle
      third of the stomach, while a biopsy suggested signet-ring cell carcinoma.
      Laboratory data showed pancytopenia, the indocyanine green fraction after 15 min
      was 29%, and the symptoms corresponded to the Child B criteria. A preoperative
      arteriogram revealed a remarkably dilated left gastric vein and the development
      of collateral pathways. We performed a distal subtotal gastrectomy with a
      reconstruction by the Billroth I method combined with a distal splenorenal shunt
      (DSRS) and a splenopancreatic disconnection (SPD). The endoscopic findings of the
      esophageal varices 15 months after surgery showed only a few white veins and the
      red color sign had disappeared. Now 7 years have passed since surgery, the risk
      of variceal hemorrhage has disappeared, and the patient is ambulatory and well.
      These results seems to be attributable to the long-term maintenance of the shunt
      selectivity and good portal hemodynamics. In patients with gastric cancer
      complicated with esophageal and/or gastric varices, it is recommended that DSRS
      with SPD be performed after a reconstruction using the Billroth I method.

PMID- 12181728
TI  - Giant cystic lymphangioma of the small bowel mesentery: report of a case.
AB  - We herein describe the case of a 48-year-old man who presented to our hospital
      with abdominal distension and pain. Preoperative studies including abdominal
      ultrasonography and computed tomography failed to determine the cause of the
      pain. At laparotomy, a giant cystic tumor of the small bowel mesentery was found.
      Histologically, the tumor was diagnosed as a cystic lymphangioma. Although
      mesenteric lymphangiomas are rare, especially in adults, they should be
      considered as a possible cause of acute abdomen.

PMID- 12181727
TI  - Gastric perforation due to the ingestion of a hollow toothpick: report of a case.
AB  - A perforation due to the ingestion of a toothpick is a condition seldom seen in
      the stomach. We herein describe an 80-year-old woman with a perforation of the
      stomach due to an ingested hollow toothpick. The toothpick was easily removed
      during a mini-laparotomy. The site of perforation was closed with absorbable
      sutures and omentum was used to function as an overlying patch. The postoperative
      course was uncomplicated. The hollow toothpick functioned as a fistula between
      the contents of the stomach and the peritoneal cavity. This resulted in a very
      different clinical picture from that observed in "classical wooden" toothpick
      injury, where the toothpick is not able to function as a fistula. To the best of
      our knowledge, this is the first description of a hollow toothpick perforating
      the stomach. A hollow toothpick perforation must be considered in any patient
      with symptoms of intestinal perforation, even when there is no history of
      swallowing toothpicks. Removal of a toothpick and subsequent suturing of the
      puncture site is a simple and relatively minor surgical procedure, which may have
      a lower morbidity and mortality as compared to other causes of gastric
      perforation. A precaution to observe, is the potential danger that one of the
      members of the operating team might perforate a finger.

PMID- 12181729
TI  - Acute fulminant necrotizing colitis caused by amebiasis: report of a case.
AB  - Fulminating colitis rarely develops as a complication of amebiasis; however, it
      is difficult to diagnose and treat, and associated with a very high mortality
      rate. We report herein the case of a 62-year-old man with superacute fulminant
      necrotizing amebic colitis who, despite treatment with aggressive surgery and
      antiamebic agents, died of multiple organ failure following sepsis on the 25th
      day after onset. The patient had no immmunosuppressive disorders and claimed that
      he had never had homosexual intercourse, or traveled to the tropics in recent
      years. Since the incidence of amebiasis is increasing in developed countries,
      including Japan, more attention should be focused on the fulminating nature of
      this disease.

PMID- 12181731
TI  - Removal of a splenic artery with a large aneurysm adhered to the pancreas without
      pancreatectomy: report of a case.
AB  - Splenic artery aneurysms account for about 60% of all visceral aneurysms. The
      treatment include surgical procedures that sometimes require pancreatectomy. This
      report describes the case of a 64-year-old woman who had multiple splenic artery
      aneurysms with various visceral artery dilatations. Because there was no obvious
      cause for the splenic artery aneurysms and other arterial abnormalities, we
      suspected an anomaly of the connective tissue, which was subsequently confirmed
      by a postoperative histopathologic examination. Thus, we decided to remove the
      whole splenic artery, to eliminate the formation of any further aneurysms, as
      well as a splenectomy. During the operation, the largest splenic artery aneurysm
      was found to be adhered to the pancreas too tightly to ablate. It initially
      appeared that pancreatectomy would be necessary, but considering the associated
      risk of postoperative complications, we tried to avoid this. Thus, we cut open
      the aneurysm and excised it, leaving the anterior wall which was adhered to the
      pancreas. Our procedure proved the best way to preserve the pancreas and
      eliminate further aneurysmal formation.

PMID- 12181730
TI  - A successful resection and long-term survival of a patient with intrahepatic
      recurrences of combined hepatocellular-cholangiocarcinoma: report of a case.
AB  - Because of the low incidence rate of combined hepatocellular-cholangiocarcinoma
      (combined HCC-CC), the clinicopathological features of a recurrent tumor of this
      disease remain to be elucidated. We describe a 47-year-old Japanese woman with a
      5-cm diameter mass lesion in the liver. A hepatectomy and dissection of the local
      lymph nodes were performed and a histological examination of the resected
      specimen showed combined HCC-CC. After a follow-up of 15 months, intrahepatic
      recurrence was observed, and a hepatectomy was performed again followed by
      hepatic arterial infusion chemotherapy. A histological examination revealed that
      the recurrent tumors consisted of only cholangioacarcinoma. A disease-free
      survival was obtained for about 7 years after the recurrence. To improve the poor
      prognosis of combined HCC-CC, clinicopathological features of this disease and
      the therapy selection for recurrent tumors should be discussed.

PMID- 12181732
TI  - Solitary splenic metastasis from ovarian cancer successfully treated by hand
      assisted laparoscopic splenectomy: report of a case.
AB  - Solitary splenic metastasis is an extremely rare phenomenon for which splenectomy
      is generally indicated because a good prognosis can be achieved if chemotherapy
      is given postoperatively. We report herein a case of solitary splenic metastasis
      from ovarian cancer, which was completely removed by hand-assisted laparoscopic
      surgery.

PMID- 12181733
TI  - Rupture of a saccular renal artery aneurysm: report of a case.
AB  - This paper reports a patient who was successfully treated for a ruptured renal
      artery aneurysm. A 64-year-old man presented with sudden onset of strong
      abdominal and lumbar pain, and a 2-week history of abdominal discomfort.
      Abdominal computed tomography and visceral arteriography revealed a
      retroperitoneal hematoma and a 7.5-cm saccular renal aneurysm with active
      bleeding. A laparotomy was indicated, and a nephrectomy was performed due to the
      persistent bleeding and refractory hypotension presented during surgery. The
      postoperative course was uneventful, and the patient was discharged with a normal
      renal function on the tenth day. This paper presents the successful management of
      a ruptured renal aneurysm with a review of the literature, and the management
      possibilities of such patients is also discussed.

PMID- 12181735
TI  - Inguinal hernia as a rare manifestation of meconium peritonitis: report of a
      case.
AB  - The usual manifestations of meconium peritonitis confined to the inguinoscrotal
      region are soft hydroceles, hard nodules in the scrotum, and, occasionally,
      calcified nodules in the wall of a hernia sac, with or without calcification on
      abdominal X-ray. Inguinal hernia is an extremely rare manifestation of healed
      meconium peritonitis. An unusual presentation of meconium peritonitis encountered
      during hernia repair is described herein to alert the pediatric surgeon of this
      possibility to avoid unnecessary abdominal exploration.

PMID- 12181734
TI  - A traumatic pseudoaneurysm of the dorsalis pedis artery: report of a case.
AB  - A 63-year old woman underwent a resection of a pseudoaneurysm in the dorsalis
      pedis artery. The aneurysm was suggested to have formed because of a bruise on
      the dorsal aspect of the foot 5 years previously. This is a rare case of a
      traumatic aneurysm in the peripheral artery.

PMID- 12181736
TI  - From the nematode and mammals back to the pine tree: on the diversity and
      evolution of programmed cell death.

PMID- 12181737
TI  - Origin licensing and programmed cell death: a hypothesis.

PMID- 12181738
TI  - 'Tissue' transglutaminase ablation reduces neuronal death and prolongs survival
      in a mouse model of Huntington's disease.
AB  - By crossing Huntington's disease (HD) R6/1 transgenic mice with 'tissue'
      transglutaminase (TG2) knock-out mice, we have demonstrated that this
      multifunctional enzyme plays an important role in the neuronal death
      characterising this disorder in vivo. In fact, a large reduction in cell death is
      observed in R6/1, TG2(-/-) compared with R6/1 transgenic mice. In addition, we
      have shown that the formation of neuronal intranuclear inclusions (NII) is
      potentiated in absence of the 'tissue' transglutaminase. These phenomena are
      paralleled by a significant improvement both in motor performances and survival
      of R6/1, TG2(-/-) versus R6/1 mice. Taken together these findings suggest an
      important role for tissue transglutaminase in the regulation of neuronal cell
      death occurring in Huntington's disease.

PMID- 12181739
TI  - XIAP inhibition of caspase-3 preserves its association with the Apaf-1 apoptosome
      and prevents CD95- and Bax-induced apoptosis.
AB  - Ligation of death receptors or formation of the Apaf-1 apoptosome results in the
      activation of caspases and execution of apoptosis. We recently demonstrated that
      X-linked inhibitor-of-apoptosis protein (XIAP) associates with the apoptosome in
      vitro. By utilizing XIAP mutants, we now report that XIAP binds to the 'native'
      apoptosome complex via a specific interaction with the small p12 subunit of
      processed caspase-9. Indeed, we provide the first direct evidence that XIAP can
      simultaneously bind active caspases-9 and -3 within the same complex and that
      inhibition of caspase-3 by the Linker-BIR2 domain prevents disruption of BIR3
      caspase-9 interactions. Recent studies suggest that inhibition of caspase-3 is
      dispensable for its anti-apoptotic effects. However, we clearly demonstrate that
      inhibition of caspase-3 is required to inhibit CD95 (Fas/Apo-1)-mediated
      apoptosis, whereas inhibition of either caspase-9 or caspase-3 prevents Bax
      induced cell death. Finally, we illustrate for the first time that XIAP mutants,
      which are incapable of binding to caspases-9 and -3 are completely devoid of anti
      apoptotic activity. Thus, XIAP's capacity to maintain inhibition of caspase-9
      within the Apaf-1 apoptosome is influenced by its ability to simultaneously
      inhibit active caspase-3, and depending upon the apoptotic stimulus, inhibition
      of caspase-9 or 3 is essential for XIAP's anti-apoptotic activity.

PMID- 12181740
TI  - Variable apoptotic response of NSCLC cells to inhibition of the MEK/ERK pathway
      by small molecules or dominant negative mutants.
AB  - To evaluate the role of the MEK/ERK pathway in NSCLC survival, we analyzed NSCLC
      cell lines that differed in tumor histology and status of p53, Rb, and K-ras.
      Constitutive ERK1/2 activity was demonstrated in 17 of 19 cell lines by
      maintenance of ERK1/2 phosphorylation with serum deprivation. Phosphorylation of
      ERK1/2 correlated with phosphorylation of MEK1/2 and p90RSK, but was inversely
      correlated with phosphorylation of c-Raf at S259. With serum deprivation, the MEK
      inhibitors, PD98059 and U0126, inhibited ERK1/2 activity but did not increase
      apoptosis. PD98059 and U0126 induced cell cycle arrest in G(0)/G(i) in cells with
      the highest levels of ERK1/2 activity, which correlated with induction of p27 but
      not p21. To confirm the cytostatic response to MEK inhibitors, we performed
      transient transfections with dominant negative forms of MEK or ERK. Surprisingly,
      dominant negative MEK and ERK mutants increased apoptosis without affecting cell
      cycle or p27 levels. When combined with paclitaxel, MEK inhibitors had no effect
      on apoptosis. In contrast, dominant negative ERK2 potentiated paclitaxel-induced
      apoptosis. Our studies show that constitutive ERK1/2 activity in NSCLC cells
      promotes cellular survival and chemotherapeutic resistance. Moreover, our data
      are the first to demonstrate divergent cellular responses to inhibition of the
      MEK/ERK pathway by small molecule inhibitors or dominant negative mutants.

PMID- 12181741
TI  - Mitomycin C induces apoptosis and caspase-8 and -9 processing through a caspase-3
      and Fas-independent pathway.
AB  - Caspase-3 activity has been described to be essential for drug-induced apoptosis.
      Recent results suggest that in addition to its downstream executor function,
      caspase-3 is also involved in the processing of upstream caspase-8 and -9. To
      test the absolute requirement for caspase-3, we examined mitomycin C (MMC)
      induced apoptosis in the caspase-3 deficient human breast cancer cell line MCF-7.
      MMC was used as anticancer drug since this agent was preferentially active
      compared to chemotherapeutic compounds with differing mechanisms of action such
      as cisplatin, docetaxel, or lovastatin. MMC treatment led to pronounced caspase
      8, -9, and -7 processing and early morphological features of apoptosis within 48
      h. This could be inhibited by the broad-spectrum caspase inhibitor z-VAD.fmk and
      to a lesser extent by z-IETD.fmk and z-LEHD.fmk, which have a certain preference
      for inhibiting caspase-8 and -9, respectively. MMC induced apoptosis in MCF-7
      cells was not mediated by the death receptor pathway as demonstrated by
      experiments using the inhibiting anti-Fas antibody ZB4 and transfections with
      CrmA, a viral serpin inhibitor of caspase-8, and the dominant negative Fas
      associated death domain (FADD-DN). Stable expression with Bcl-2 significantly
      prevented the processing of caspase-9 but also of caspase-8 and blocked the
      induction of apoptosis. Thus, we provide evidence that caspase-3 activity is
      dispensable for MMC-induced apoptosis and for caspase-8 and -9 processing in MCF
      7 cells.

PMID- 12181743
TI  - Reovirus-induced apoptosis requires both death receptor- and mitochondrial
      mediated caspase-dependent pathways of cell death.
AB  - Apoptosis plays an important role in the pathogenesis of many viral infections.
      Despite this fact, the apoptotic pathways triggered during viral infections are
      incompletely understood. We now provide the first detailed characterization of
      the pattern of caspase activation following infection with a cytoplasmically
      replicating RNA virus. Reovirus infection of HEK293 cells results in the
      activation of caspase-8 followed by cleavage of the pro-apoptotic protein Bid.
      This initiates the activation of the mitochondrial apoptotic pathway leading to
      release of cytochrome c and activation of caspase-9. Combined activation of death
      receptor and mitochondrial pathways results in downstream activation of effector
      caspases including caspase-3 and caspase-7 and cleavage of cellular substrates
      including PARP. Apoptosis is initiated by death receptor pathways but requires
      mitochondrial amplification producing a biphasic pattern of caspase-8, Bid, and
      caspase-3 activation.

PMID- 12181742
TI  - Caspase cleavage of the nuclear autoantigen LEDGF/p75 abrogates its pro-survival
      function: implications for autoimmunity in atopic disorders.
AB  - Lens epithelium-derived growth factor p75 (LEDGF/p75) is a nuclear autoantigen in
      atopic disorders implicated in cellular protection against stress-induced
      apoptosis. We observed that LEDGF/p75 was cleaved during apoptosis into fragments
      of 65 and 58 kD generated by caspases-3 and -7 cleaving at three sites:
      DEVPD30/G, DAQD486/G and WEID85/N. Sequence analysis revealed that the DEVPD30/G
      and WEID85/N sites lie within the highly conserved HATH (homologous to amino
      terminus of hepatoma-derived growth factor) region, also known as PWWP domain.
      Alignment of proteins containing this domain failed to reveal conservation of the
      DEVPD30/G and WEID85/N sites, suggesting that the HATH/PWWP domain of LEDGF/p75
      may be specifically targeted by caspases. Overexpression of LEDGF/p75 protected
      HepG2 cells from serum starvation-induced cell death, whereas expression of the
      65 kD fragment failed to protect. The apoptotic cleavage of LEDGF/p75 may
      contribute to the pathogenesis of atopic disorders by abrogating its pro-survival
      function and enhancing its immunogenicity.

PMID- 12181745
TI  - Spontaneous apoptosis in primary cultures of human and rat hepatocytes: molecular
      mechanisms and regulation by dexamethasone.
AB  - To elucidate the biochemical pathways leading to spontaneous apoptosis in primary
      cultures of human and rat hepatocytes, we examined the activation of the caspase
      cascade, the expression of Bcl-2-related-proteins and heat shock proteins.
      Comparisons were made before and after dexamethasone (DEX) treatment. We show
      that DEX inhibited spontaneous apoptosis in a dose-dependent manner. DEX
      increases the expression of anti-apoptotic Bcl-2 and Bcl-x(L) proteins, decreases
      the expression of pro-apoptotic Bax and inhibits Bad translocation thereby
      preventing the release of cytochrome c, the activation of caspases, and cell
      death. Although, the expression of Hsp27 and Hsp70 proteins remained unchanged,
      the oncogenic protein c-Myc is upregulated upon DEX-treatment. These results
      indicate that DEX mediates its survival effect against spontaneous apoptosis by
      acting upstream of the mitochondrial changes. Thus, the mitochondrial apoptotic
      pathway plays a major role in regulating spontaneous apoptosis in these cells.
      Blocking this pathway therefore may assist with organ preservation for
      transplant, drug screening, and other purposes.

PMID- 12181746
TI  - Deoxyribonuclease IIalpha is required during the phagocytic phase of apoptosis
      and its loss causes perinatal lethality.
AB  - Deoxyribonuclease IIalpha (DNase IIalpha) is one of many endonucleases implicated
      in DNA digestion during apoptosis. We produced mice with targeted disruption of
      DNase IIalpha and defined its role in apoptosis. Mice deleted for DNase IIalpha
      die at birth with many tissues exhibiting large DNA-containing bodies that result
      from engulfed but undigested cell corpses. These DNA-containing bodies are
      pronounced in the liver where fetal definitive erythropoiesis occurs and extruded
      nuclei are degraded. They are found between the digits, where apoptosis occurs,
      and in many other regions of the embryo. Defects in the diaphragm appear to cause
      death of the mice due to asphyxiation. The DNA in these bodies contains 3'
      hydroxyl ends and therefore stain positive in the TUNEL assay. In addition,
      numerous unengulfed TUNEL-positive cells are observed throughout the embryo.
      Apoptotic cells are normally cleared rapidly from a tissue; hence the persistence
      of the DNA-containing bodies and TUNEL-positive cells identifies sites where
      apoptosis occurs during development. These results demonstrate that DNase IIalpha
      is not required for the generation of the characteristic DNA fragmentation that
      occurs during apoptosis but is required for degrading DNA of dying cells and this
      function is necessary for proper fetal development.

PMID- 12181744
TI  - Release of cytochrome c and activation of pro-caspase-9 following lysosomal
      photodamage involves Bid cleavage.
AB  - Photodynamic therapy (PDT) protocols employing lysosomal sensitizers induce
      apoptosis via a mechanism that causes cytochrome c release prior to loss of
      mitochondrial membrane potential (DeltaPsi(m)). The current study was designed to
      determine how lysosomal photodamage initiates mitochondrial-mediated apoptosis in
      murine hepatoma 1c1c7 cells. Fluorescence microscopy demonstrated that the
      photosensitizer N-aspartyl chlorin e6 (NPe6) localized to the lysosomes.
      Irradiation of cultures preloaded with NPe6 induced the rapid destruction of
      lysosomes, and subsequent cleavage/activation of Bid, pro-caspases-9 and -3. Pro
      caspase-8 was not activated. Release of cytochrome c occurred at about the time
      of Bid cleavage and preceded the loss of DeltaPsi(m). Extracts of purified
      lysosomes catalyzed the in vitro cleavage of cytosolic Bid, but not pro-caspase-3
      activation. Pharmacological inhibition of cathepsin B, L and D activities did not
      suppress Bid cleavage or pro-caspases-9 and -3 activation. These studies
      demonstrate that photodamaged lysosomes trigger the mitochondrial apoptotic
      pathway by releasing proteases that activate Bid.

PMID- 12181747
TI  - MEK/ERK pathway protects ionizing radiation-induced loss of mitochondrial
      membrane potential and cell death in lymphocytic leukemia cells.
AB  - MEK/ERK-mediated signals have recently been found to inhibit Fas-mediated cell
      death through inhibition of caspase-8 activity. It remains unknown whether
      MEK/ERK-mediated signals affect ionizing radiation (IR)-induced cell death. Here
      we demonstrate that MEK/ERK-mediated signals selectively inhibit IR-induced loss
      of mitochondrial membrane potential (DeltaPsi(m)) and subsequent cell death. In
      Jurkat cells, TPA strongly activated ERK and inhibited the IR-induced caspase
      8/Bid cleavage and the loss of DeltaPsi(m). The inhibitory effect of TPA was
      mostly abrogated by pretreatment of a specific MEK inhibitor PD98059, indicating
      that the effect depends upon MEK/ERK-mediated signals. Moreover, BAF-B03
      transfectants expressing IL-2 receptor (IL-2R) beta(c) chain lacking the acidic
      region, which is responsible for MEK/ERK-mediated signals, revealed higher
      sensitivity to IR than the transfectants expressing wild-type IL-2R.
      Interestingly, the signals could neither protect the DeltaPsi(m) loss nor cell
      death in UV-irradiated cells. These data imply that the anti-apoptotic effect of
      MEK/ERK-mediated signals appears to selectively inhibit the IR-induced cell death
      through protection of the DeltaPsi(m) loss. Our data enlighten an anti-apoptotic
      function of MEK/ERK pathway against IR-induced apoptosis, thereby implying its
      contribution to radioresistance.

PMID- 12181748
TI  - Propapoptotic effects of NF-kappaB in LNCaP prostate cancer cells lead to serine
      protease activation.
AB  - LNCaP prostate cancer cells are resistant to induction of apoptosis by gamma
      irradiation and partially sensitive to TNF-alpha or FAS antibody, irradiation
      sensitizes cells to apoptosis induced by FAS antibody or TNF-alpha. LNCaP cell
      clones stably expressing IkappaBalpha super repressor were resistant to apoptosis
      induced by death ligands in the presence or absence of irradiation. IkappaBalpha
      super repressor expression also increased clonogenic survival after exposure to
      TNF-alpha+irradiation, but had no effect on survival after irradiation alone.
      IkappaBalpha super repressor expression blocked the increase of whole cell and
      cell surface FAS expression induced by TNF-alpha, but did not effect induction of
      FAS expression and cell surface FAS expression that resulted from irradiation. In
      cells expressing IkappaBalpha super repressor there was diminished activation of
      caspases-8 and -7 and diminished production of proscaspases-8 and -7, usually
      required for death induction in LNCaP cells. Peptide inhibitors of caspase
      activation complemented the IkappaBalpha super repressor inhibition of apoptosis,
      but peptide inhibitors of serine proteases had no effect on LNCaP cells
      expressing IkappaBalpha super repressor. Moreover, cleavage of a serine protease
      substrate was induced by treatment of LNCaP cells with TNF-alpha and irradiation.
      The data suggest that in LNCaP cells NF-kappaB mediates a proapoptotic pathway
      that leads to activation of proapoptotic serine proteases.

PMID- 12181749
TI  - Tipping the balance between necrosis and apoptosis in human and murine cells
      treated with interferon and dsRNA.
AB  - Interferons enhance the cellular antiviral response by inducing expression of
      protective proteins. Many of these proteins are activated by dsRNA, a typical by
      product of viral infection. Here we show that type-I and type-II interferons can
      sensitize cells to dsRNA-induced cytotoxicity. In caspase-8- or FADD-deficient
      Jurkat cells dsRNA induces necrosis, instead of apoptosis. In L929sA cells dsRNA
      induced necrosis involves high reactive oxygen species production. The
      antioxidant butylated hydroxyanisole protects cells from necrosis, but shifts the
      response to apoptosis. Treatment with the caspase inhibitor benzyloxycarbonyl-Val
      Ala-DL-Asp(OMe)-fluoromethylketone or overexpression of Bcl-2 prevent this shift
      and promote necrosis. Our results suggest that a single stimulus can initiate
      different death-signaling pathways, leading to either necrotic or apoptotic cell
      death. Inhibition of key events in these signaling pathways, such as caspase
      activation, cytochrome c release or mitochondrial reactive oxygen species
      production, tips the balance between necrosis and apoptosis, leading to dominance
      of one of these death programs.

PMID- 12181750
TI  - Expression and transcriptional regulation of caspase-14 in simple and complex
      epithelia.
AB  - Caspase-14 is a recent addition to the caspase family of aspartate proteases
      involved in apoptotic processes. Human caspase-14 appears to be only weakly
      processed during apoptosis, and it does not cleave classical caspase substrates.
      Post partum, caspase-14 is prominently expressed by human keratinocytes and
      reportedly participates in terminal differentiation of complex epithelia. Here we
      provide evidence challenging the view that caspase-14 expression or processing is
      linked exclusively to terminal keratinocyte differentiation. We demonstrate that
      caspase-14 expression extended to multiple cell lines derived from simple
      epithelia of the breast, prostate, and stomach. In keratinocytes and breast
      epithelial cells, caspase-14 expression was upregulated in high-density cultures
      and during forced suspension culture. These effects were primarily due to
      transcriptional activation as indicated by reporter gene assays using a 2 kb
      caspase-14 promoter fragment. Importantly, caspase-14 was not cleaved during
      forced suspension culture of either cell type although this treatment induced
      caspase-dependent apoptosis (anoikis). Forced expression of caspase-14 in
      immortalized human keratinocytes had no effect on cell death in forced suspension
      nor was the transfected caspase-14 processed in this setting. In contrast to
      postconfluent and forced suspension culture, terminal differentiation of
      keratinocytes induced in vitro by Ca2+ treatment was not associated with
      increased caspase-14 expression or promoter activity. Our results indicate that
      (1) caspase-14 is expressed not only in complex but also simple epithelia; (2)
      cells derived from complex and simple epithelia upregulate caspase-14 expression
      in conditions of high cell density or lack of matrix interaction and; (3) in both
      cell types this phenomenon is due to transcriptional regulation.

PMID- 12181751
TI  - Early redox imbalance mediates hydroperoxide-induced apoptosis in mitotic
      competent undifferentiated PC-12 cells.
AB  - Our recent study has demonstrated that cellular redox imbalance can directly
      initiate apoptosis in a mitotic competent PC-12 cell line without the involvement
      of reactive oxygen species (ROS). However, whether cell apoptosis induced by ROS
      is, in fact, mediated by a loss of redox balance caused by the oxidant is
      unresolved. The linkage between oxidant-mediated apoptosis and the induction of
      cellular redox was examined in PC-12 cells using the oxidant, tert
      butylhydroperoxide (TBH). TBH caused cell apoptosis in 24 h that was preceded by
      an early increase (30 min) in oxidized glutathione (GSSG). Pretreatment with N
      acetyl cysteine prevented TBH-induced GSSG increases and cell apoptosis. Altered
      Bax/BcL-2 expression and release of mitochondrial cytochrome c occurred post
      redox imbalance and was kinetically linked to caspase-3 activation and poly ADP
      ribose polymerase cleavage. Moreover, cell apoptosis was attenuated by inhibition
      of caspase-9, but not caspase-8, and blockade of mitochondrial ROS generation and
      permeability transition pore attenuated caspase 3 activation and cell apoptosis.
      Collectively, these results show that TBH-induced GSSG elevation is associated
      with the disruption of mitochondrial integrity, activation of caspase-3 and cell
      apoptosis. This redox induction of the apoptotic cascade was dissociated from
      cellular GSH efflux.

PMID- 12181752
TI  - Key role of mitochondria in cerulenin-mediated apoptosis.
AB  - Cerulenin, a fungal metabolite, is known to be a specific inhibitor of fatty acid
      synthase. Here we report that cerulenin is an effective inducer of apoptosis in
      different wild-type p53 and mutant p53 tumor cell lines, whereas normal human
      keratinocytes and fibroblasts are resistant to the apoptotic effect. To get more
      insight into the mechanisms of how cerulenin induces apoptosis we investigated
      several signal transduction molecules, including p53, p73, p21/WAF1, Bax,
      cytochrome c, and caspases 3 and 9. Our data strongly indicate that mitochondria
      play a key role in the cerulenin-mediated pathway. Bax overexpression correlated
      with the extent of apoptosis and appears to be regulated in a p53-independent
      manner. The significance of the mitochondrial pathway for the cerulenin-mediated
      apoptosis was confirmed by the rapid mitochondrial release of cytochrome c both
      in wild-type p53 and mutant cell lines. Interestingly, the rapid release of
      cytochrome c was not accompanied by a breakdown of the mitochondrial potential.
      Instead, the complete disruption of the mitochondrial function coincided with the
      appearance of a p18 kDa cleavage product of Bax.

PMID- 12181753
TI  - Death on the beach: a rosy forecast for the 21st century.

PMID- 12181754
TI  - [Not Available].
AB  - BACKGROUND: In this review we wanted to explane of opinions of The Turkish
      Association for Trauma and Emergency Surgery monthly inter-hospital meetings
      results. METHODS: Opinions of meetings participants about blunt abdominal trauma
      were reviewed. RESULTS: Haemodynamic stability and conscience situation are the
      main factors to determine the approach to blunt abdominal trauma patients. We
      generally prefer ultrasonography (USG) to first step diagnostic technique for
      haemodynamica/ly stable patients. IfUSG is not possible, diagnostic
      peritoneallavage (DPL) could be perform. We propose that DPL or USGcould be
      perform when the focus isnot known in the haemodynamica/ly unstable, multi
      traumatised patients. But we don 't agree to perform any diagnostic techniques if
      we know that haemodynamic unstability is caused from intraperitoneal injury.
      CONCLUTION: We prefer and propose resuscitation and emergency laparotomy for a/l
      patients of whom focus of the haemodynamica/ly un-stability is i1itra-abdominal
      damage. But ifthe haemodynamica/ly un-stable patients have pelvic bone fractures
      we don't propose the emergency laparotomy, because the probablefocus ofthe
      serious bleeding is pelvic vessels. In our opinion that patients must be
      resuscitated aggressively and evaluated with C1; because in this situations false
      positivity of the DPL is often. Surgeons must not take shelter the laparotomy for
      the name of life rescue, because negative and non- therapeutic laparotomy has
      high morbidity.

PMID- 12181755
TI  - Abdominal compartment syndrome.
AB  - OBJECTIVE: To invstigte the physiologic effects and therapeutic management ofthe
      abdominal kompartm sendrome (ACS) METHODS: A review ofthe recent Iiterature,
      experiences and opinions ofthe author are expressed in the papei: RESULTS AND
      CONCLUSIONS: Intraabdominal bleeding, peritonitis, ileus, shock-reperfusion
      syndrome, intestinal edema, Iaparoscopic procedures with gas, ciosure ofthe
      abdomen in spite ofincreased pressure and burns are some ofthefactors that take
      place in etiology. The critical intrabdominal pressure value that requires
      decompression is debatable. In patients with high abdominal pressures, the
      pressure should be decreased with Iaparotomy immediately and the abdomen should
      not be ciosed primarily. These measures will help us to Iower the rates of
      mortality and morbidity and improve the quality ofhealth services.

PMID- 12181756
TI  - Effects of granulocyte colony-stimulating factor (g-csf) on neutrophil
      phagocytosis during experimental obstructive jaundice.
AB  - BACKGROUND: Obstruction ofthe extrahepati(biliary tree produces profound
      depression of many components ofthe immune system. G-CSF improves
      diseasedfiinction fneutrophils in various conditions. In this study, we planned
      to investigate the changes on neutrophil phagocytosis in obstruct;ve jaundice and
      the effect ofG-CSF adm;nistration on thisfiinction. METHODS: Rats were divided
      into 5 groups as follows: the sham group and four other groups that underwent
      double ligation and division of common bile duct. Two of these four groups (Group
      3 and 5) received G-CSF during experiment. Neutrophil hagocytosis index was
      determinedforgroup2and 3 attheend ofthe 15 daysand forgroup 1, 4and 5 attheend of
      the21 days. RESULTS: Neutrophil phagocytosis index significantly increased at the
      end ofthe 15th day after the bile duct ligation (Group 2) and significantly
      decreased at the end ofthe 21th day after the bile duct ligation (Group 4).
      Neutrophil phagocytosis index in G-CSF-treated groups was significantly increased
      at the end ofthe 15'h days (Group 3) and increased at the end of the 21th day
      (Group 5). CONCLUTION: As a result, neutrophil phagocytosis index is improved if
      G-CSF is administered later in the course of prolonged jaundice.

PMID- 12181757
TI  - [Peptic ulcer perforation: an analysis of risk factors].
AB  - BACKGROUND: Despite decreasing incidence of peptic ulcer disease, peptic ulcer
      perforation remains a source of mortality. This retrospective study was performed
      to find riskfactors for mortality and to construct a score that predict outcome
      for patients with peptic ulcer perforation. METHODS: A review of94 patients
      operated (primer ciosure and omentoplasty) for perforated peptic ulcer in Iast
      ten years was undertaken to study. lndependent risk factors for mortality were
      found with Iinear regression analysis and risk score was constructed using
      standardized coefficients of risk factors. RESULTS: Acute renal failure (ARF) (p
      < 0,00 1 ), treatment delay more than 48 hours (> =48 hours) (p = 0,203 ) and age
      greater than 60 years (> 60 years) (p = 0, 199) were found signijicant factors
      independently injuencing mortality. The risk score was (Risk score = (ARF)XO,497
      + (> =48 hours)XO,203 + (>60years)XO,199). The overall predictive accuracy of
      risk score was%95. CONCLUTION: Treatment delay and related acute renal failure
      and advanced age are determining factors for survival after ulcer perforation.
      Delay of treatment may be only changeable factor for mortality. lt is ciear that,
      the early diagnosis and treatment aredecreasing operative mortality of peptic
      ulcer perforation. Every effort to decrease the mortality should be this mannei:

PMID- 12181758
TI  - [STAGED ABDOMINAL REPAIR (STAR) PROCEDURES IN OUR CLlNIC].
AB  - AIM: In this study we assessed the results of staged abdominal repair (STAR)
      applications in our clinic. METHODS: Retrospective analysis ofsix cases who were
      operated by staged abdominal repair (STAR) between December 1998-1January 2002
      were assessed according to operation indications, type of operation, presentation
      ofthe complications and mortality. RESULTS: The initial operations for two
      ischemic bowel disease cases were right hemicolectomy + end ileostomy + mucous
      fistula and partial small bowel resection + right hemicolectomy +
      ileotransversostomy. The operative indications were fistula formation following
      strangulatedfemoral hernia, diverticular perforation, diverticulitis + massive
      lower gastrointestinal bleeding and abdominal ! gunshot trauma, and operations
      were right hemicolectomy + ileotransversostomy, subtotal colectomy +
      ileorectostomy + diverting ileostomy, subtotal colectomy + Hartmann procedure and
      primary repair of vena cava + distal pancreatectomy + left hemicolectomy+
      Hartmann procedure respectively. Median hospital stay was 28 days. Two cases had
      pulmonary problems (pleural effiision and 1 atelectasis). Gunshot trauma patient
      died four days after the abdominal closure probably due to pulmonary emboli.
      CONCLUTIONS: Relaparotomy decision may be made prior to the operation but the
      final decision is made per-operatively. Staged abdominal repair gives an
      opportunity for sufficient debridement and peritoneallavage and also gives a
      chance to evaluate the anastomosis sites.

PMID- 12181759
TI  - [PROGNOTIC FACTORS EFFECTING MORTALlTY IN TRAUMATIC DIAPHRAGMA INJURY].
AB  - BACKGROUND: Traumatic diaphragma rupturesare difficult to diagnose and generally
      with associated organe injuries. The aim ofthe study is to evaluate the factors
      effect on mortality. METHODS: Twenty-three patients with traumatic diaphragma
      injuries, admitted to our hospital were retrospectively evaluated for
      demographics, diagnosis, otherorgan injuries, treatment, mortalityand morbidity.
      RESULTS: All patients were male and the mean age was 24.7  10.0. The diaphragma
      injuries were observed during laparatomy in 19 patients (%82.6), during
      laparatomy and thoracotomy in 2 (%8.7). The injuries were diagnosed with fluid
      drainage from thorax tube during peritoneal lavage in 2 patients (%8. 7). All
      patients, but one, had other organ injuries (%95.7), most commonly in stomach,
      spleen and liver. Seven patients died during peroperative or postoperative peiod
      (%30.4). When these seven patients were compared to survived patients, it was
      observed that age and trauma score were statistically related to mortality rate
      (p<0.05), but the lenght ofthe diaphragmatic injury was not related to mortality
      rate (p > 0.05). CONCLUSION: Traumatic diaphragma injuries are generally
      diagnosed during laparatomy and associated with other organ injuries. The high
      mortality rate in patients with traumatic diaphragma injuries, is not related to
      the characteristics ofthe diaphragma injury, but it is closely related to
      concomitant problems such as patient is age and trauma score.

PMID- 12181760
TI  - [Epidemiologic evaluation of trauma cases admitted to a pediatric emergency
      service].
AB  - BACKGROUND: This study was performed to contribute epidemiological data about
      pediatric trauma registry in our country. METHODS: Ninety-four children with
      trauma who were admitted to the Pediatric Emergency Clinic of our hospital were
      prospectively evaluated. RESULTS: Forty-five percent patients were female and 55%
      were male with a mean age of 79+52 months. Traffic accidents were the primary
      cause of trauma (46%). The education level of the mothers were above high school
      in only 30.4 % patients. Forty-four percent of trauma took place during daytime,
      the incidence of trauma was high in summer and autumn (p<0.05). Eighteen percent
      of patients required major and 31 % of patients required minor surgical treatment
      whereas 48% of patients were conservatively treated and 3% died. Forty-seven
      percent of patients were referred to our hospital from another hospital and
      surgical intervention requirement for referred patients were found to be higher
      than the others (p<0.05). CONCLUSION: Increasing the education level if mothers
      will contribute to the prevention of childhood trauma. KEYWORDS: Pediatric
      trauma, childhood, epidemiology

PMID- 12181762
TI  - [LOCKED INTRAMEDULLARY NAlLlNG OF HUMERAL SHAFT FRACTURES].
AB  - BACKGROUND: Clinical and radiological results ofthe patients with humeral
      shaftfractures who underwent Iocked intramedullary nailing are retrospectively
      evaluated in this study. METHODS: 29 patients (17 males, 12 females; mean age
      43.6; range 26 to 68 years) who underwent Iocked intramedullary nailing were
      evaluated retrospectively. 17 patients had major and seven patients had minor
      traumas. ln three patients the fractures were, pathological and also two patients
      had additional hypertrophic non-union. Closed intramedullary nailing was
      performed in 21 patients. Three patients (two with non-union) were treated by
      using autogenous graft. Nine patients were nailed antegradely and 20
      retrogradely. RESULTS: The meanfollow-up period was 16.2 months (range 8 to 47
      months). The mean time ofunion was 18 weeks (range 8 to 36 weeks) in 26 patients
      (% 90) but non-union occured in three patients.Functional end results
      ofshoulderand elbow were excellent in 23 (%79) patients, moderate infour (%13)
      patients and bad in two %8) patients. Postoperative complications included radial
      nerve palsy, breakaie of the distal locking screw and superficial infection in
      one patient each. Nail migration also occured in an osteoporotic patient.
      CONCLUTIONS: Locked intramedullary nailing is the treatment ofchoicefor humeral
      shaftfractures in osteopenic bone, pathological fractures, comminuted or
      segmentalfractures and also for humeral shaftfractures in polytraumatised
      patients who may need to use the injured armfor early rehabilitation and
      mobilization.

PMID- 12181761
TI  - [Ambulance in emergency medicine].
AB  - BACKGROUND: The ambulance service is very important in emergency medicine. The
      aim of this study was to investigate the new governing statuate of private
      ambulance service and to propose some new ideas. METHODS: We examinated the new
      governing statuate of private ambulance service, rules of patient transporte
      between the hospitals and reports written by SSK Goztepe Educational Hospital
      ambulance drivers. CONCLUTION: We concluded that SSK Goztepe Educational Hospital
      ambulance drivers have a iot of problems especially at the rules of patient
      transport between the hospitals and there are some defiencies at the new
      governing statuate of private ambulance service. RESULTS: We concluded that it is
      necesssary to manage all the ambulance services in one center; all the private
      ambulance services have to have a specialist and all these must be determinated
      by the special rules. Key words: Regulation ofprivate ambulance, emergency head
      maintanence, ambulance services

PMID- 12181763
TI  - [Risk of compartment syndrome in open and closed tibial fractures].
AB  - BACKGROUND: In orthopaedic traumatology; acute compartment syndrome is a common
      complication associated with tibial fractures. In our study, we investigate
      differences, if any, between open and closed tibialfractures in terms oftheir
      risk of compartment syndrome. METHODS: Fourty-two tibial fractures of 39
      patients, 29 (69%) closed and 13 (31%) open, having the risk of acute compartment
      syndrome according to the clinical examination, were monitored following traumas
      during which their DP (DP= Diastolic blood pressure -Absolute compartment
      pressure) and absolute compartment pressures were measured via intracompartmental
      pressure measuring equipment. RESULTS: Average absolute compartment pressure was
      found to be 31.25 mmHg in open and 29,32 mmHg in closed fractures (p=O,484)
      whereas average DP was measured to be 47,46 mmHg in open and 49,66 mmHg in
      closedfractures (p=O,415). According to student's test, the difference between
      the two groups was not significant. We found the incidence of acute compartment
      syndrome as 7, 7% in open fractures, 6.9% in closed and 7, 1 % in overall tibial
      fractures andfasciotomy was carried out in those cases. CONCLUTION: Statistically
      not significant difference between the pressure levels,found in open and closed
      tibialfractures, showed that open type oftibialfractures holds the risk of
      compartment syndrome as much as the closed one.

PMID- 12181764
TI  - [Rupture of an incidental giant liver hemangioma caused by blunt abdominal
      trauma].
AB  - A patient with blunt abdokminal trauma due to a traffic accident was admitted to
      our clinic and operated urgently because of hemodynamic shock. Operative
      exploration revealed rupture of a congenital giant cavernous liver hemangioma,
      then a partial hepatic resection was performed. Liver abscess and pleural
      effusion occurred in the postoperative period and the abscess was drained by a CT
      guided cathetei: However the catheter drainage get infected. As a conclusion, if
      a liver hemangioma is detected incidentally on routine check-up studies, these
      people, carrying potential risk ofrupture should be warned about high risk jobs.

PMID- 12181765
TI  - [Bouveret'S syndrome: gastric outlet obstruction by a gallstone].
AB  - This rare syndrome first described by Bouveret in 1896, occurs when a stone
      migrates through a cholecysto or choledochoduodenal jistula lodging in the
      duodenal bulb and resulting in obstruction. Up to date, less than 100 cases
      reported in the literature. This rare type of gallstone ileus can be diagnosed
      and treated endoscopically, although there are a few previous reports of
      successful endoscopic, removal. However, surgical removal is safe and effective
      but the most controversial aspect is the proper treatment, simple enterotomy and
      removal ofthe gallstone alone or enterolithotomy in association with
      cholecystectomy and dejinitive correction ofthe biliodigestive fistula. This
      paper presents a case report of a 65 year old man with gastric outlet obstruction
      caused by a large gallstone. The diagnose and treatment of this case who was
      admitted in 1.General Surgical Department of Taksim Teaching and Research
      Hospital was researched under the reference of recent literature.

PMID- 12181766
TI  - [A rare cause of acute abdomen in childhood: primary omental torsion].
AB  - We examined the fact that 12 years old obese girl who applied to our clinic with
      acute abdomen symptoms and we determined primer omental torsion (POT) at
      laparotomy in this case. This disease is rare in childhood and imitates the signs
      of acute appendicitis. Obesity and anatomic variations ofthe omentum are
      predisposingfactorsfor POI ln this study we wanted to share our experiences in
      diagnosis and treatment ofPOI

PMID- 12181767
TI  - [Self migrating intracranial bullets].
AB  - We report herein two patients in whom bullets migrated into adjacent lateral
      ventricles in the brain and moved freely as a consequence of gravity. A rewiew
      ofthe literature suggests that spontaneous migration ofintracerebral bullets is
      being eased by cerebral softness, specific gravity of the bullet compared with
      brain tissue. ln patients undergoing the surgical removal of intracerebral or
      intraventricular bullets, an x-ray is recommended after final positioning.

PMID- 12181768
TI  - [Unrealistic promises, one-sided presentations, constructive expectations].

PMID- 12181769
TI  - [Therapeutic factors of outpatient group psychotherapy - the predictive validity
      of the Group Experience Questionnaire (GEQ)].
AB  - It was the aim of the study to investigate different factors of group experience
      in relation to therapy effects and to prove the predictive validity of the Group
      Experience Questionnaire (GEQ); for this purpose for each scale of the GEQ the
      values of later "Responders" and "Non Responders" were compared. The sample
      consisted of 50 patients with psychosomatic diseases who where treated with
      outpatient integrated psychodynamic group therapy. We found that the GEQ is able
      to differentiate between successful and less successful patients. Especially the
      therapeutic factors "autonomy and optimism" as well as "well-being" are of high
      predictive value. Contrary to former investigations the therapeutic factor
      "cohesion" was less important, which could hint at the fact that a medium amount
      of cohesion might be sufficient for an effective process of treatment.

PMID- 12181770
TI  - [Nicotine dependence and motivation for smoking cessation in patients of a
      cardiologic-pneumologic department].
AB  - Tobacco cessation interventions are cost effective therapies in the secondary
      prevention of coronary heart and chronic obstructive pulmonary diseases which
      however are rarely used in Germany. Therefore the frequency and the degree of
      tobacco addiction, the previous treatment of tobacco abuse and the present
      motivation for smoking cessation of all patients treated within one month in a
      department of cardiology/pneumology were assessed. 255 of 264 admitted patients
      (39 % women, 61 % men, mean age 65 +/- 13 years) were evaluated. 33/255 patients
      (13 %) were smokers, 110/255 (43 %) were former smokers and 112/255 (44 %)
      patients never smoked. 25/33 (76 %) of the smoking patients met the criteria of
      nicotine dependence and 8/33 (24 %) the criteria of nicotine abuse of the DSM-IV.
      According to the Fagerstrom-Nicotine-Dependence-Test (FTND) 6/33 (18 %) smokers
      were low nicotine dependent (FTND 0 - 3 points), 24/33 (73 %) smokers were
      moderate nicotine dependent (FTND 4 - 7 points) and 3/33 (9 %) smokers were high
      nicotine dependent (FTND 8 - 10 points). 8/33 patients (24 %) agreed in, 8/33
      patients (24 %) were undecisive with regard to and 17/33 (52 %) smokers refused
      smoking cessation treatment during their hospital stay. There was no difference
      in the FTND between patients willing to stop smoking and patients which were
      undecisive or unwilling to stop smoking. 27/33 (82 %) patients were pointed to
      the existence of a tobacco induced disease by physicians, 14/33 (42 %) had
      received informations about smoking cessation, 7/33 (21 %) had received nicotine
      substitution and 3/33 (9 %) other treatments (smoking cessation training,
      acupuncture) in the past. Motivation for and realization of smoking cessation
      interventions should be considered as important tasks of the psychosomatic or
      addiction primary care in private practices and hospitals.

PMID- 12181771
TI  - [Religious and spiritual beliefs - validation of the German version of the
      "Systems of Belief Inventory" (SBI-15R-D) by Holland et al. in a population-based
      sample].
AB  - The present study describes the German version of the "Systems of Belief
      Inventory (SBI-15R)" developed by Holland et al. The questionnaire was used in a
      representative sample of 954 eastern and 1031 western Germans. The SBI met tests
      of internal consistency and demonstrated discriminant validity. But the two
      factors of the original version could not clearly be replicated. For the
      relevance of religious beliefs we found that women score higher than men, older
      score higher than younger, persons with lower education score higher than persons
      with higher education, western Germans score higher than eastern Germans.
      Connections between the SBI-15R-D and self-evaluation as being religious and
      importance of faith during childhood give hints to the instrument's validity. The
      SBI-15R-D can serve as a valid and economic tool to explore the role of religious
      and spiritual beliefs.

PMID- 12181772
TI  - [Recalled parental rearing and the wish to have a child - are there
      associations?].
AB  - The present study concerns the impact of recalled parental rearing behaviour on
      both the intensity of the wish to have a child and on different motives to have a
      child. Until now there are no empirical studies as to this objective. Our study
      is based on a representative sample of 1509 persons aged 18 to 50 years. The
      statistical analyses were restricted to those subjects who lived in partnership
      and reported an actual wish to have a child (n = 331). The data were assessed by
      self-reporting scales: The Questionnaire of Recalled Parental Rearing Behaviour
      "Fragebogen zum erinnerten elterlichen Erziehungsverhalten, FEE", the Partnership
      Questionnaire "Partnerschaftsfragebogen, PFB", and the Leipzig Questionnaire of
      Motives to Have a Child "Leipziger Fragebogen zu Kinderwunschmotiven, LKM". A
      recalled parental rearing behaviour, which was characterized as having been
      rejective, overprotective and less emotionally warm was associated with such
      motives which do not promote the wish to have own children (fear of personal
      restrictions and a low degree of social support). Simultaneously, a negative
      parental rearing behaviour was correlated with a stronger desire for social
      recognition by an own child. The recalled maternal rearing behaviour was
      altogether stronger associated with motives to have a child than the paternal. On
      the other hand, no relevant associations could be found between the recalled
      parental rearing behaviour and the intensity of the wish to have a child.

PMID- 12181773
TI  - [Psychiatric comorbidity in medical inpatients - prevalence and effect on the
      length of stay].
AB  - In the course of a year the prevalence of psychiatric comorbidity as well as the
      effect of psychiatric comorbidity on the length of stay on two internal medical
      wards we investigated. When examined by separate methods, the prevalence of
      psychiatric comorbidity reached 36 % (ICD-10 diagnosis) in a sample of 511
      medical inpatients of a university hospital. The study shows that patients with
      psychiatric comorbidity have a significantly longer length of stay - up to 8.2
      days compared with inpatients with mere internal diagnosis. This association was
      not influenced by the length and the severity of the illness. The findings lead
      to the conclusion that psychiatric comorbidity is a central contributor to one of
      the most important factors of medical costs - the length of stay.

PMID- 12181775
TI  - Power calculations for a general class of family-based association tests:
      dichotomous traits.
AB  - Using large-sample theory, we present a unified approach to power calculations
      for family-based association tests. Currently available methods for power
      calculations are restricted to special designs or require approximations or
      simulations. Our analytical approach to power calculations is broadly applicable
      in many settings. We discuss power calculations for two scenarios that have high
      practical relevance and in which power previously could only be assessed by
      simulation studies or by approximations: (1) studies using both affected and
      unaffected offspring and (2) studies with missing parental information. When the
      population prevalence is high, it can be worthwhile to genotype unaffected
      offspring. For many scenarios, high power can be achieved with reasonable sample
      sizes, even when no parental information is available.

PMID- 12181774
TI  - DNA sequence variation in a 3.7-kb noncoding sequence 5' of the CYP1A2 gene:
      implications for human population history and natural selection.
AB  - CYP1A2 is a cytochrome P450 gene that is involved in human physiological
      responses to a variety of drugs and toxins. To investigate the role of population
      history and natural selection in shaping genetic diversity in CYP1A2, we
      sequenced a 3.7-kb region 5' from CYP1A2 in a diverse collection of 113
      individuals from three major continental regions of the Old World (Africa, Asia,
      and Europe). We also examined sequences in the 90-member National Institutes of
      Health DNA Polymorphism Discovery Resource (PDR). Eighteen single-nucleotide
      polymorphisms (SNPs) were found. Most of the high-frequency SNPs found in the Old
      World sample were also found in the PDR sample. However, six SNPs were detected
      in the Old World sample but not in the PDR sample, and two SNPs found in the PDR
      sample were not found in the Old World sample. Most pairs of SNPs were in
      complete linkage disequilibrium with one another, and there was no indication of
      a decline of disequilibrium with physical distance in this region. The average +/
      SD nucleotide diversity in the Old World sample was 0.00043+/-0.00026. The
      African population had the highest level of nucleotide diversity and the lowest
      level of linkage disequilibrium. Two distinct haplotype clusters with broadly
      overlapping geographical distributions were present. Of the 17 haplotypes found
      in the Old World sample, 12 were found in the African sample, 8 were found in
      Indians, 5 were found in non-Indian Asians, and 5 were found in Europeans.
      Haplotypes found outside Africa were mostly a subset of those found within
      Africa. These patterns are all consistent with an African origin of modern
      humans. Seven SNPs were singletons, and the site-frequency spectrum showed a
      significant departure from neutral expectations, suggesting population expansion
      and/or natural selection. Comparison with outgroup species showed that four
      derived SNPs have achieved high (>0.90) frequencies in human populations, a trend
      consistent with the action of positive natural selection. These patterns have a
      number of implications for disease-association studies in CYP1A2 and other genes.

PMID- 12181778
TI  - Miss B.

PMID- 12181776
TI  - Dissecting the genetic complexity of the association between human leukocyte
      antigens and rheumatoid arthritis.
AB  - Rheumatoid arthritis (RA) is an inflammatory disease with a complex genetic
      component. An association between RA and the human leukocyte antigen (HLA)
      complex has long been observed in many different populations, and most studies
      have focused on a direct role for the HLA-DRB1 "shared epitope" in disease
      susceptibility. We have performed an extensive haplotype analysis, using 54
      markers distributed across the entire HLA complex, in a set of 469 multicase
      families with RA. The results show that, in addition to associations with the
      DRB1 alleles, at least two additional genetic effects are present within the
      major histocompatibility complex. One of these lies within a 497-kb region in the
      central portion of the HLA complex, an interval that excludes DRB1. This genetic
      risk factor is present on a segment of a highly conserved ancestral A1-B8-DRB1*03
      (8.1) haplotype. Additional risk genes may also be present in the HLA class I
      region in a subset of DRB1*0404 haplotypes. These data emphasize the importance
      of defining haplotypes when trying to understand the HLA associations with
      disease, and they clearly demonstrate that such associations with RA are complex
      and cannot be completely explained by the DRB1 locus.

PMID- 12181777
TI  - Contribution of BRCA1 and BRCA2 mutations to breast and ovarian cancer in
      Pakistan.
AB  - The population of Pakistan has been reported to have the highest rate of breast
      cancer of any Asian population (excluding Jews in Israel) and one of the highest
      rates of ovarian cancer worldwide. To explore the contribution that genetic
      factors make to these high rates, we have conducted a case-control study of 341
      case subjects with breast cancer, 120 case subjects with ovarian cancer, and 200
      female control subjects from two major cities of Pakistan (Karachi and Lahore).
      The prevalence of BRCA1 or BRCA2 mutations among case subjects with breast cancer
      was 6.7% (95% confidence interval [CI] 4.1%-9.4%), and that among case subjects
      with ovarian cancer was 15.8% (95% CI 9.2%-22.4%). Mutations of the BRCA1 gene
      accounted for 84% of the mutations among case subjects with ovarian cancer and
      65% of mutations among case subjects with breast cancer. The majority of detected
      mutations are unique to Pakistan. Five BRCA1 mutations (2080insA, 3889delAG,
      4184del4, 4284delAG, and IVS14-1A-->G) and one BRCA2 mutation (3337C-->T) were
      found in multiple case subjects and represent candidate founder mutations. The
      penetrance of deleterious mutations in BRCA1 and BRCA2 is comparable to that of
      Western populations. The cumulative risk of cancer to age 85 years in female
      first-degree relatives of BRCA1-mutation-positive case subjects was 48% and was
      37% for first-degree relatives of the BRCA2-mutation-positive case subjects. A
      higher proportion of case subjects with breast cancer than of control subjects
      were the progeny of first-cousin marriages (odds ratio [OR] 2.1; 95% CI 1.4-3.3;
      P=.001). The effects of consanguinity were significant for case subjects with
      early-onset breast cancer (age <40 years) (OR=2.7; 95% CI 1.5-4.9; P=.0008) and
      case subjects with ovarian cancer (OR=2.4; 95% CI 1.4-4.2; P=.002). These results
      suggest that recessively inherited genes may contribute to breast and ovarian
      cancer risk in Pakistan.

PMID- 12181779
TI  - Interview with Align Technology executives. Interview by David L Turpin.

PMID- 12181780
TI  - [Experimental study on growth factor in promotion of chondrocytes proliferation].
AB  - OBJECTIVE: To study the effect of two cytokines, basic fibrolast growth
      factor(bFGF) and insulin-like growth factor-I(IGF-I), on cell proliferation in
      chondrocytes of adult rabbits. METHODS: The primary chondrocytes of adult rabbits
      were harvested and cultured with bFGF and IGF-I at different concentrations,
      respectively, as well as with the mixture of the two cytokines; the quantity of
      cultured chondrocytes was detected by MTT assay at the 24th, 48th and 72nd hours;
      and the final fold increase of different groups was measured by cell count for
      the 3rd passage; and the proliferation index of the groups was recorded by
      flowing cytometer on the 14th day. RESULTS: 1. The cultured chondrocytes with
      either bFGF, IGF-I or their mixture were significantly more than that of control
      group at the 24th, 48th and 72th hours (P < 0.01). 2. After the 3rd passage, the
      final folds of proliferation were significantly higher in the groups with
      cytokines than in the control group (P < 0.01); and the final fold with the
      mixture of cytokines was significantly higher than that of both IGF-I and bFGF (P
      < 0.01). 3. The proliferation index was significantly higher in the groups with
      cytokines than in the control group (P < 0.01); the proliferation index with the
      mixture of cytokines was significantly higher than that of both IGF-I and bFGF (P
      < 0.05); besides, proliferation index was higher when cytokine was applied twice
      than once (P < 0.05); besides, proliferation index was higher when cytokine was
      applied twice than once (P < 0.05). CONCLUSION: bFGF and IGF-I could promote
      chondrocytes proliferation of adult rabbits obviously and they are synergistic in
      cell proliferation.

PMID- 12181781
TI  - [Experimental study on repair of articular cartilage defect in large area with
      chondrocytes cultured on fascia].
AB  - OBJECTIVE: To study the biological characteristic and potential of chondrocytes
      grafting cultured on fascia in repairing large defect of articular cartilage in
      rabbits. METHODS: Chondrocytes of young rabbits were isolated and sub-cultured on
      fascia. The large defect of articular cartilage was repaired by grafts of freeze
      preserved and fresh chondrocytes cultured on fascia, and free chondrocytes
      respectively; the biological characteristic and metabolism were evaluated by
      macroscopic, histological and immunohistochemical observations, autoradiography
      method and the measurement of nitric oxide content 6, 12, 24 weeks after
      grafting. RESULTS: The chondrocytes cultured on fascia maintained normal growth
      feature and metabolism, and there was no damage to chondrocytes after
      cryopreservation; the repaired cartilage was similar to the normal cartilage in
      cellular morphology and biological characteristics. CONCLUSION: Chondrocytes
      could be cultured normally on fascia, which could be used as an ideal carrier of
      chondrocytes.

PMID- 12181782
TI  - [Effect of insulin-like growth factor-I on cultured articular chondrocytes of
      rabbits].
AB  - OBJECTIVE: To investigate the influence of insulin-like growth factor-I (IGF-I)
      on biological characteristics of articular chondrocytes cultured in vitro of
      rabbits. METHODS: Monolayer articular chondrocytes of 4-week old rabbits were
      cultured in medium with IGF-I, at the concentrations of 3, 10, 30, 100, and 300
      ng/ml. The DNA content in cells and glucuronic acid content in matrix were
      detected on the 2nd, 4th, 6th days after culture. RESULTS: The DNA content in
      cells and the glucuronic acid content in matrix in articular chondrocytes
      cultured in medium with IGF-I at concentrations of 3-300 ng/ml were all
      significantly higher than those in control group (P < 0.01), which reached the
      peak at the concentrations of 30-100 mg/ml on the 4th day. CONCLUSION: IGF-I
      could obviously promote the proliferation of articular chondrocytes in vitro, and
      there exist time-dependent and dose-dependent effect.

PMID- 12181783
TI  - [Clinical study on surgical repair of acute acromioclavicular dislocation by
      modified Weaver-Dunn technique].
AB  - OBJECTIVE: To investigate the clinical value of modified Weaver-Dunn technique in
      repair of acute acromioclavicular dislocation. METHODS: From January 1993 to
      December 1998, 18 cases of acromioclavicular dislocation were treated by modified
      Weaver-Dunn technique, and other 17 cases of the same suffering were treated by
      tension band fixation of the acromioclavicular joints. All of the patients were
      followed up for 12-36 months before clinical evaluation of the function of
      shoulder joints, according to University of Pennsylvanian Shoulder Score System.
      RESULTS: In short term, the shoulder joints recovered much more rapidly in the
      cases repaired by modified Weaver-Dunn technique; 12, 24 and 36 months after
      operation, the scores of the cases repaired by modified Weaver-Dunn technique
      were (189.7 +/- 6.7), (193.7 +/- 3.6) and (194.7 +/- 3.4) respectively according
      to the Shoulder Score System, while those of the cases treated by tension band
      fixation were (167.3 +/- 7.8), (170.2 +/- 6.3) and (165.6 +/- 5.9) respectively.
      The above data indicated that there was significant difference between two groups
      (P < 0.05). CONCLUSION: The modified Weaver-Dunn technique was a better surgical
      approach than tension band fixation for repair of acute acromioclavicular
      dislocation.

PMID- 12181784
TI  - [Treatment of elbow joint ankylosis by repair of articular surface with
      periosteal autograft].
AB  - OBJECTIVE: To evaluate the clinical effect of periosteal autograft in repair of
      ankylosis of elbow joint. METHODS: From May 1985 to November 1999, 18 cases of
      elbow joints ankylosis (6 cases of osteo-ankylosis, 12 cases of fibroankylosis)
      were treated by repairing articular surface with periosteal autografting. Out of
      18 cases, 13 were caused by old dislocation and fracture of elbow joints, 3 by
      late rheumatoid arthritis, and 2 by old total joint tuberculosis. In this
      surgical approach, periosteum from upper end of tibia was transplanted into
      articular surface after correction of the elbow joint from ankylosis deformity,
      and continuous passive or active movement of the operated joint was adopted with
      skeletal traction through olecranon of ulna for 4 weeks after operation. All of
      the cases were followed up for 1-9 years, 5.2 years on average, before clinical
      evaluation. RESULTS: The elbow joints in 11 cases were restored to normal, the
      joints in 4 cases obtained active movement in the range of 100 degrees-0 degree,
      and the joints in the other 3 cases could only have limited movement because of
      severe muscular atrophy. CONCLUSION: The articular surface in arthroplasty of
      elbow joint ankylosis could be effectively repaired by periosteal autograft, and
      the function of the joints could be obviously improved by continuous movement of
      the joints after operation with skeletal traction.

PMID- 12181785
TI  - [Repair of cartilage defect of knee joints with free periosteal autograft].
AB  - OBJECTIVE: To investigate the clinical application of periosteal autograft in
      repair of cartilage defect caused by osteoarthritis of knee. METHODS: From 1996
      to 1999, 36 knees of cartilage defect of knee joint in 28 cases were treated. In
      the operation, the cracked degenerative cartilage was removed before free
      periosteum from tibia was transplanted to repair the defect, and the meniscuses
      in 8 kness of the 36 knees were reconstructed. After operation, early continuous
      passive movement was adopted for 4 weeks, and 8 knees with reconstruction of the
      meniscus were immobilized by plaster splint for 7 days after operation and before
      passive movement. All of the cases were followed up for 1 to 4 years before
      clinical evaluation in symptoms, signs and radiological findings. RESULTS: The
      general satisfactory rate was 86.1%, in which the function was excellent in 22
      knees and good in 9 knees. CONCLUSION: The periosteal autograft is a good choice
      for repairing cartilage defect due to osteoarthritis, with a satisfactory outcome
      in the short term.

PMID- 12181786
TI  - [Clinical study on chitosan in prevention of knee adhesion after patellar
      operation].
AB  - OBJECTIVE: To investigate the clinical effect of chitosan in prevention of knee
      dysfunction due to adhesion after operation for patellar fracture. METHODS: From
      March to October 1999, 40 cases of patellar fracture were treated by internal
      fixation, with intra-articular injection of 2% chitosan in only 24 cases after
      fixation and with no chitosan injection in 16 cases (control group). The function
      of the knee joint, including extension and flexion, was evaluated 1 month and 1
      year after operation respectively. RESULTS: One month after operation, the knees
      with chitosan injection could actively move in the average range of 104 degrees
      +/- 23 degrees, and the knees in the control group could move in the average
      range of 72 degrees +/- 16 degrees, which showed significant difference between
      two groups (P < 0.01); 1 year after operation, the range of movement of the knees
      with injection was 165 degrees +/- 38 degrees on average, and that of the knees
      in the control group was 110 degrees +/- 31 degrees, which also indicated
      significant difference between two groups (P < 0.05). CONCLUSION: Medical
      chitosan could effectively prevent or reduce the post-operative adhesion of knee
      joint after patellar operation.

PMID- 12181787
TI  - [Treatment of calcaneal interarticular fracture by open reduction and internal
      fixation].
AB  - OBJECTIVE: To investigate the clinical outcome of open reduction and internal
      fixation of calcaneal interarticular fractures. METHODS: From August 1998, 38
      calcanneal interarticular fractures in 35 cases, including 8 of type II, 14 of
      type III and 16 of type IV according to Sander's classification, were treated by
      open reduction to restore the posterior articular facet, subtalar facet, Bohler
      angle and Gissane's angle, following internal fixation by plastic titanic alloy
      plate. Thirty-three calcanneal interarticular fractures were followed up for 6 to
      22 months, 12.3 months on average; and the healing time and joint function were
      evaluated according to Maryland Foot Score System. RESULTS: The average healing
      time of fracture was 7.1 weeks, ranging from 5 to 12 weeks; and the joint
      function was excellent in 18 calcanneus, good in 13 calcanneus, and the
      satisfactory rate was 93.9%. CONCLUSION: Open reduction and internal fixation
      with plastic titanium plate is a good choice for calcanel interarticular
      fractures.

PMID- 12181788
TI  - [Function of fibula in stability of ankle joint].
AB  - OBJECTIVE: To summarize the function of fibula in stability of ankle joints.
      METHODS: Recent original articles were extensively reviewed, which were related
      to the physiological function and biomechanical properties of fibula, the
      influence of fibular fracture on stability of ankle joints and mechanism of
      osteoarthritis of ankle joints. RESULTS: The fibula had the function of weight
      bearing; and it was generally agreed that discontinued fibula could lead to intra
      articular disorder of ankle joint in children; but there were various viewpoints
      regarding the influence of fibular fracture on the ankle joint in adults.
      CONCLUSION: Fibula may play an important role in stability of ankle joint.

PMID- 12181789
TI  - [Experimental study on transplantation of acellular xeno-dermis and suspended
      keratinocytes].
AB  - OBJECTIVE: To investigate the outcome and histological changes of transplantation
      of acellular xeno-dermis combined with suspended keratinocytes. METHODS: Forty
      two nude mice with full-thickness skin defect on the back were randomly divided
      into 2 groups, then acellular xeno-dermisand and suspended keratinocytes were
      adopted to cover the skin defect in the experimental group, pure suspended
      keratinocytes in the control group. The area of wound healing was calculated 2, 3
      and 5 weeks after transplantation, and the rates of wound contraction were also
      calculated, and biopsy for histological examination was performed 3, 6 and 12
      weeks after transplantation. RESULTS: Compared with the experimental group, the
      control group showed delayed wound healing (P < 0.05), intensive wound
      contraction (P < 0.05), poor durability, elasticity, and cosmetic appearances as
      well as disordered collagen fibers. In contrast, it was observed that the
      proliferation of collagen fibers was regularly organized, with no obvious acute
      immuno-rejection responses in the experimental group. CONCLUSION: The composite
      transplantation of acellular xenodermis and suspended keratinocytes could promote
      the wound healing with a satisfactory outcome.

PMID- 12181790
TI  - [Characteristics and effect of three transforming growth factor-beta isoforms and
      their receptor(I) on scar formation].
AB  - OBJECTIVE: To observe the differences in protein contents of three transforming
      growth factor-beta (TGF-beta) isoforms, beta 1, beta 2, beta 3 and their
      receptor(I) in hypertrophic scar and normal skin and to explore their influence
      on scar formation. METHODS: Eight cases of hypertrophic scar and their
      corresponding normal skin were detected to compare the expression and
      distribution of TGF-beta 1, beta 2, beta 3 and receptor(I) with
      immunohistochemistry and common pathological methods. RESULTS: Positive signals
      of TGF-beta 1, beta 2, and beta 3 could all be detected in normal skin, mainly in
      the cytoplasm and extracellular matrix of epidermal cells; in addition, those
      factors could also be found in interfollicular keratinocytes and sweat gland
      cells; and the positive particles of TGF-beta R(I) were mostly located in the
      membrane of keratinocytes and some fibroblasts. In hypertrophic scar, TGF-beta 1
      and beta 3 could be detected in epidermal basal cells; TGF-beta 2 chiefly
      distributed in epidermal cells and some fibroblast cells; the protein contents of
      TGF-beta 1 and beta 3 were significantly lower than that of normal skin, while
      the change of TGF-beta 2 content was undistinguished when compared with normal
      skin. In two kinds of tissues, the distribution and the content of TGF-beta R(I)
      had no obviously difference. CONCLUSION: The different expression and
      distribution of TGF-beta 1, beta 2 and beta 3 between hypertrophic scar and
      normal skin may be associated with the mechanism controlling scar formation, in
      which the role of the TGF-beta R (I) and downstream signal factors need to be
      further studied.

PMID- 12181791
TI  - [Effect of exogenous hyaluronan on wound healing].
AB  - OBJECTIVE: To investigate the mechanism of impeded wound healing by exogenous
      hyaluronan (HA). METHODS: Wound healing models were established on 18 adult
      rabbit ears, which were randomly divided into 3 groups, the 2% HA treated-group
      (group A), the 1% HA treated-group(group B), and the PBS control group (group C).
      The process of wound healing was observed morphologically and histologically. The
      expression of alpha-smooth muscle actin in fibroblast was measured by
      immunohistochemical method. RESULTS: 1. The mean values of wound healing time of
      groups A, B and C were (11.7 +/- 0.6), (11.3 +/- 0.6), and (10.8 +/- 1.0) days
      respectively. Wound contraction was greater in group C than in group A and group
      B. 2. Compared with PBS controls, the collagen fibril was slender and arrayed
      regularly in HA treated wound. 3. The expression of alpha-smooth muscle actin was
      greater in group C than in groups A and B. CONCLUSION: It is one of reasons of
      impeded wound healing that exogenous HA inhibits the expression of alpha-smooth
      muscle protein and wound contraction. There exists dose-dependent effect.

PMID- 12181792
TI  - [Experimental study on bacteriostasis of chitosan and sodium hyaluronate].
AB  - OBJECTIVE: To compare the effect and coverage of bacteriostasis of chitosan and
      sodium hyaluronate. METHODS: Each of the five bacteria, Proteus mirabilis,
      Escherichia coli, Candida albicans, Pseudomonas aeruginosa, Staphylococcus
      aureus, was cultivated for 33 tubes of broth culture. Leaving three tubes each
      group as control group, ploidy diluted concentration of high relative molecular
      weight chitosan, low relative molecular weight chitosan and sodium hyaluronate
      were added respectively in the broth culture. All the tubes were cultivated for
      18 hours at 37 degrees C with homeothermia. Then the growth of bacteria was
      observed. RESULTS: The minimal inhibitory concentrations (MIC) of high relative
      molecular weight chitosan were: Proteus mirabilis 0.031%, Escherichia coli
      0.063%, Candida albicans 0.063%, Pseudomonas aeruginosa 0.063%, Staphylococcus
      aureus 0.063%; and the MIC of low relative molecular weight chitosan were:
      Proteus mirabilis 0.125%, Escherichia coli 0.025%, Candida albicans 0.25%,
      Pseudomonas aeruginosa 0.25%, Staphylococcus aureus 0.125%; bacteria grew well in
      each tube of sodium hyaluronate group and control group. CONCLUSION: The above
      results show that sodium hyaluronate has no bacteriostasis, while chitosan has
      bacteriostasis on broad spectrum and high relative molecular weigh: chitosan has
      stronger effect.

PMID- 12181793
TI  - [Proliferative ability of the central area tenocytes of flexor tendons in vitro].
AB  - OBJECTIVE: To study the healing ability of the central area tissue of flexor
      tendons after injury. METHODS: Tendons of flexor digitorum profundus of the long
      toes from 8 white Leghorn hens were harvested in zone II. Tissues were cut in 4
      mm segments and divided into the experimental group (the central area tissue of
      flexor tendons) and the control group (the tendon segments without epitenon).
      There were 12 tendon segments cultured in each group. Specimens were obtained and
      examined under light microscope on the 9th, 18th and 27th days after culture,
      respectively. Another 4 tendons were used as normal control, and they were
      directly examined under light microscope. RESULTS: The number of tenocytes was
      significantly less in the control group than in the experimental group and the
      uncultured state (P < 0.01); the number of tenocytes was significantly higher in
      the experimental group than in the uncultured state (P < 0.01). The number of
      tenocytes of the experimental group were higher on the 9th day than on the 18th
      and 27th days after culture(P < 0.01). CONCLUSION: The central area tissue of
      flexor tendons has favorable healing ability after injury.

PMID- 12181794
TI  - [Clinical study on two internal fixation methods Kaneda and Z-plate in the
      operation of anterior surgical approach after thoracolumbar fractures].
AB  - OBJECTIVE: To study the difference between two internal fixation methods Kaneda
      and Z-plate in the operation of anterior surgical approach and decompression
      after thoracolumbar fractures. METHODS: The bio-mechanical structure of the
      internal fixture, install when operating, complications and time of the operation
      were compared in the cases by Kaneda and Z-plate. RESULTS: Z-plate method had the
      following characteristics: reasonable of the bio-mechanical structure; stability
      after internal fixture being installed; capability of completely propping up the
      injured centrum and keeping the height of middle-column; simple operation when
      installing internal fixture and shorter time of operation (1.1 hours, P < 0.05);
      fewer complications. CONCLUSION: Z-plate is an ideal internal fixation method in
      the operation of anterior surgical approach after thoracolumbar fractures.

PMID- 12181796
TI  - [Application of tissue flaps in repair of limbs injuries].
AB  - OBJECTIVE: To summarize and analyze the main point on the reconstruction of
      traumatic tissue defects of limbs with vascularized skin and multi-tissue flaps.
      METHODS: Sixty-seven cases of traumatic tissue defects of limbs were
      reconstructed with 14 kinds of skin or multi-tissue flaps. The operative methods
      included local transposition, cross-transposition with vessel pedicles and vessel
      anastomosed free transplantation. RESULTS: Forty cases with vessel anastomosed
      free transplantation and 26 cases with local or cross-transposition of vessel
      pedicled flaps were survived. In the followed up cases, 53 cases were satisfied
      with the outward appearance of the skin flaps. All the cases with bone flap or
      skin-bone flap resulted in union. And the cases with motor nerve anastomosed
      myocutaneous flap transplantation had recovered to 2-3 grade muscle contraction
      ability. CONCLUSION: It is important that the appropriate flaps and operative
      methods should be chosen according to the size, location, depth and structure of
      the tissue defects. To raise the success rate and to gain better operation
      effect, the correct manipulation in operation and the rational postoperative
      treatment are necessary.

PMID- 12181795
TI  - [Treatment of fracture of neck of femur in the aged with hollow compression
      screw].
AB  - OBJECTIVE: To summarize the clinical results of hollow compression screw in
      treatment of fracture of neck of femur in the aged. METHODS: From November 1993
      to October, 1998, 52 aged patients with several types of fracture of neck of
      femur were treated; among them, there were 25 males and 27 females aged from 60
      to 83 years (70 years on average). There were 48 cases of fresh fracture and 4
      cases of old fracture. Forty-two cases were performed closed reduction internal
      fixation, 10 cases with open reduction internal fixation. RESULTS: All the
      patients could sit by themselves 4 to 6 days after operation, and could walk with
      a crutch 10 to 15 days after operation. The mobility of hip joint was nearly
      normal 4 weeks after operation. All the patients were followed 26 to 84 months,
      48.5 months on average. Bone union was achieved in 50 cases, nonunion in 2 cases.
      The average healing time was 4.7 months. There were no other complications, such
      as ankylosis and muscular atrophy, but ischemic necrosis in 3 cases. CONCLUSION:
      This method has following advantages, convenient manipulation, less injury,
      stable fixation, and the short-term recovery, which avoid some common
      complications. It is a reliable method worthy of popularizing.

PMID- 12181797
TI  - [Effect of endogenous carbon monoxide on oxidant-mediated multiple organ injury
      following limb ischemia-reperfusion in rats].
AB  - OBJECTIVE: To determine the role of endogenous carbon monoxide(CO) in oxidant
      mediated organ injury following limb ischemia-reperfusion (I/R) in rats. METHODS:
      Sixty-four SD rats were divided into 4 groups: Sham group, Sham + zinc
      protoporphyrin (ZnPP, an inhibitor of heme oxygenase activity), 2-hour ischemia
      followed by 4-hour reperfusion (I/R) group and I/R + ZnPP group.
      Carboxyhemoglobin (COHb) level in the artery blood, malondialdehyde (MDA) content
      and superoxide dismutase (SOD) activity in the lung, heart, liver and kidney were
      detected. The 24-hour survival rate of rats was studied. RESULTS: Compared with
      the sham group, the COHb level and MDA content significantly increased, while the
      SOD activity and the survival rate significantly decreased in I/R group (P <
      0.05). Compared with the I/R group, MDA content significantly increased, while
      the SOD activity, the 24-hour survival rate and COHb level significantly
      decreased in I/R + ZnPP group (P < 0.05, respectively). CONCLUSION: Limb I/R
      could lead to the oxidant-mediated multiple organ injury accompanied by the
      increase of CO level which play an important role in the defense against I/R
      induced remote multiple organ injury in rats.

PMID- 12181798
TI  - [Potential seeding cells for cartilage tissue engineering--bone marrow stromal
      stem cells].
AB  - OBJECTIVE: To review the recent research progress of bone-marrow stromal stem
      cells (BMSCs) in the conditions of culture in vitro, chondrogenic
      differentiation, and the application in cartilage tissue engineering. METHODS:
      Recent original articles related to such aspects of BMSCs were reviewed
      extensively. RESULTS: BMSCs are easy to be isolated and cultivated. In the
      process of chondrogenesis of BMSCs, the special factors and interaction between
      cells are investigated extensively. BMSCs have been identified to form cartilage
      in vivo. One theory is the committed chondrocyte from BMSCs is only a transient
      stage. CONCLUSION: BMSCs are the alternative seeding cells for cartilage tissue
      engineering. The conditions promoting mature chondrocyte should be further
      investigated.

PMID- 12181800
TI  - [The advances in immunological research on xenotransplantation].
AB  - OBJECTIVE: To investigate the mechanism of xenotransplantation rejection and the
      interaction between the immunocytes. METHODS: This review concluded the research
      achievements and new advances in xenotransplantation based on the relevant
      experimental data. RESULTS: Transgenic pig technology and novel
      immunosuppressants were applied to suppress hyperacute rejection and acute
      vascular rejection respectively. Modulation of T cell and antigen presenting
      cells and induction of tolerance were taken for the prevention of acute cellular
      rejection. CONCLUSION: In general, the technology of transgenic pig is relatively
      mature and effective. The mechanism and prevention of acute vascular rejection
      and acute cellular rejection should be further investigated.

PMID- 12181799
TI  - [Effect of combined application of external cyclosporine A and CTLA4Ig on the
      survival of rat auricle allograft].
AB  - OBJECTIVE: To study the effect of combined application of external cyclosporine A
      (CsA) and CTLA4Ig in inhibiting rejection and inducing immune tolerance in
      composite tissue allograft. METHODS: The auricles with vessel pedicle were
      transplanted from Lewis rats to BN rats under microsurgery. CsA was spreaded on
      the surface of grafts in combination with administration of CTLA4Ig
      intraperitoneally after transplantation. The rejection response and survival time
      of grafts were observed, and the IL-2 level in serum was measured. RESULTS: The
      mean survival time was (7.8 +/- 1.7) days in control group. It was (15.2 +/- 1.9)
      days when recipients treated by CsA and (16.6 +/- 2.1) days by CTLA4Ig. Under the
      combination of CsA and CTLA4Ig, the mean survival time was significantly
      prolonged to (28.8 +/- 3.5) days (P < 0.05) with the lowest level of IL-2 in
      serum of recipients. CONCLUSION: The combined application of external CsA and
      CTLA4Ig inhibits rejection of allograft effectively, which can be a favorable
      therapy on composite tissue allo-transplantation.

PMID- 12181801
TI  - Recent inspectional trends: are regulatory requirements for sterile products
      becoming scientifically undoable or unpractical?

PMID- 12181803
TI  - Sterile filtration--a review of the past and present technologies.

PMID- 12181802
TI  - Helium leak test for sterility assurance of a sealed bag. I: Relationship of
      helium leak and pinhole diameter.
AB  - Described herein is an attempt to establish a simpler, more reliable method to
      maintain the aseptic condition of bulk materials of drug substances. The method
      would be used in the manufacturing process of our "double-bag" kit system for
      infusion, which has two compartments, one for the infusion liquid and another for
      the drug product. To manufacture the kit system, we used a flexible inner
      container to enclose the bulk under aseptic conditions and a method for ensuring
      sterility of the container. We used an aluminum laminate bag as the inner
      container, which was then enclosed in a polyethylene bag. To detect tears or
      pinholes in the bag, a helium leak test was evaluated. First, a simple
      experimental model of helium leakage from bags was established. In the model, a
      pinhole was made in a film disk of the aluminum laminate or polyethylene material
      used for the inner and outer bags. A helium leak detector was used to measure the
      escape of helium through the pinhole, and the leak could be detected from a
      pinhole from 10 microns in diameter. As the bulk product was doubly sealed in an
      aluminum bag and a polyethylene bag in the manufacturing process to maintain an
      aseptic condition, we also checked for helium leak from pinholes of film disks
      after connecting two film disks. The results showed that helium leak was
      detectable when the pinhole diameters of both film disks were more than 20
      microns. Clearly, helium leak is strongly affected by pinhole diameter in both
      experimental models. We have calculated, for the pinhole geometries studied,
      helium leak rates by using the Poiseuille Equation. Calculated values were in
      agreement with experimental values.

PMID- 12181804
TI  - Determination of residual moisture in lyophilized protein pharmaceuticals using a
      rapid and non-invasive method: near infrared spectroscopy.
AB  - This study examined the application of near-infrared (NIR) spectroscopy to
      analyze residual moisture in lyophilized protein pharmaceuticals sealed in glass
      vials. We demonstrated that NIR was able to determine residual moisture in five
      marketed and clinical products with the same precision as Karl Fischer titration.
      We further investigated how changes in product configuration and protein
      formulation affected NIR measurement accuracy using a lyophilized monoclonal
      antibody rhuMAb E25 containing 1% to 5% residual moisture. The results indicated
      that the lyophilized cake porosity and dimensions had no effect on NIR
      measurement when the cake height and diameter exceeded the NIR penetration depth.
      In addition, changing the buffer and surfactant concentrations in the formulation
      did not affect moisture determination by NIR. However, doubling or halving the
      concentration of a disaccharide, which was used as a lyoprotectant, caused
      significant deviation between the NIR and Karl Fischer data because the NIR
      absorbance of the disaccharide overlapped with the moisture signal. Furthermore,
      complete removal of the disaccharide resulted in alteration of the protein NIR
      spectra, suggesting that NIR may be used to evaluate solid-state protein
      structure. The disaccharide concentration must be kept constant in this
      formulation to obtain accurate moisture results by NIR.

PMID- 12181805
TI  - Validation of the Scan RDI for routine microbiological analysis of process water.
AB  - In this report, we review the validation methods and criteria specified in the
      PDA Technical Report No. 33 "Evaluation, Validation, and Implementation of New
      Microbiological Testing Methods" against data generated on the Chemunex Scan RDI.
      For each parameter, we have either reported data obtained in-house or reviewed
      information and documentation available from the manufacturer of the system. For
      all specified requirements, the Scan RDI produced data that was within the
      specifications suggested in the PDA Technical Report or suitable information was
      obtained from the manufacturer. The results of the study indicate that the Scan
      RDI can be validated for routine use in a pharmaceutical environment and provide
      results equivalent to current methods, but in a much shorter time frame.

PMID- 12181806
TI  - Wet heat inactivation of lipopolysaccharide from E. coli serotype 055:B5.
AB  - Wet heat inactivation of lipopolysaccharide (LPS) from E. coli Serotype 055:B5
      was investigated. The LPS solutions were heated at study temperatures ranging
      from 78 degrees C to 175 degrees C, and were assayed using the Limulus Amebocyte
      Lysate (LAL) test. Plots of the log of the amount of endotoxin remaining versus
      heating time showed biphasic decreases. The initial slopes are associated with a
      faster rate of decrease to about a 0.5-log unit reduction, and were followed by a
      slower, linear rate of decline in the secondary slopes. The curves were applied
      to the biexponential model expressed by the equation (Et = E1e-klt + E2e-k2t).
      The LPS inactivation rates (k1 and k2) each conformed to their own Arrhenius
      equation. Therefore, the processes required to achieve the desired level of LPS
      inactivation can be obtained by mathematical means.

PMID- 12181807
TI  - [Experience in application of modified ballistic cardiography in assessment of
      contractile myocardial function in patients with coronary atherosclerosis].
AB  - Complex examination of myocardial contractility (MC) including modified
      (vertical) ballistocardiography (MBCG) covered 109 patients with coronary
      atherosclerosis. The MBCG registers early MC defects typical for patients with
      coronary atherosclerosis, ischemic heart disease. It is highly sensitive.
      Algorithms for diagnosis of the above defects have been developed. MBCG can be
      widely used in practical cardiology as a highly informative method for MC
      evaluation.

PMID- 12181808
TI  - [24-hour arterial hypertension profile and heart rhythm variability in patients
      with arterial hypertension and NIDDM].
AB  - The study covered 72 patients with non-insulin-dependent diabetes mellitus
      (NIDDM) whose mean age was 54.2 +/- 0.8 years, duration of the disease 8.6 +/-
      3.6 years. They had also mild or moderate arterial hypertension mean duration of
      which was 12.4 +/- 4.3 years. The examination of the patients consisted of 24-h
      arterial pressure (AP) monitoring, Holter ECG monitoring, cardiointervalography.
      For eight weeks 19 patients received enalapril (5-20 mg/day), 14 patients were
      given felodipin (5-10 mg/day) and 15 patients were treated with valsartan (80-160
      mg/day). Enhanced activity of the sympathetic nervous system in hypertensive
      subjects with NIDDM raises daily average values of systolic and diastolic AP,
      variability and speed of AP morning rise. In NIDDM patients with moderate
      arterial hypertension vegetative regulation of AP was more stressed than in mild
      hypertension. Optimal medication of NIDDM patients' arterial hypertension may
      consist of ACE inhibitors and antagonists of angiotensin II receptors. These drug
      lower stress of the sympathetic nervous system and thus promote normalization of
      daily profile of AP.

PMID- 12181809
TI  - [Specification of rheumatic fever contribution to formation of senile aortic
      stenosis].
AB  - Calcinated aortic stenosis developing in the elderly is erroneously referred to
      atherosclerotic lesion of the valve or is thought to be rheumatic heart defect
      undetected previously. The atherosclerotic hypothesis is rejected by foreign
      investigated while a conception of postrheumatic damage is discussed in the light
      of immune inflammation found in the calcinated valve. Immunogenetic testing was
      used for investigation of correlations between senile aortic stenosis and
      rheumatic fever.

PMID- 12181810
TI  - [The study of partial tension of blood oxygen and forced expiration in patients
      with chronic obstructive bronchitis receiving inhalation of hypertonic salt
      solution].
AB  - To ascertain side effects of aerosol therapy which implies use of concentrated
      hypertensive salt solution (HSS), patients with chronic obstructive bronchitis
      (COB) and marked obstructive ventilation disturbances on HSS inhalation treatment
      were examined for PaO2 and bronchial patency. It was established that HSS
      inhalations do not affect PaO2 in COB patients. This expands opportunities for
      design of aerosol technology and its practical applications.

PMID- 12181811
TI  - [Cardiac syndrome in females with systemic undifferentiated dysplasia of the
      connective tissue].
AB  - The trial enrolled 119 women with systemic undifferentiated dysplasia of the
      connective tissue (DCT) aged 14-39 years; 86.6% of them had asthenic
      constitution. Ultrasound most frequently found prolapse of mitral cusps and
      accessory chord as in the left ventricle. Use of chest x-ray, echocardiography,
      ECG 24-h monitoring and transesophageal pacing discovered combination of heart
      dislocation, changed intracardiac structures, disturbed rhythm and conduction in
      87 examinees. This provided the diagnosis of dysplastic heart syndrome. Multiple
      significant correlations between echocardiometric parameters, hormonal indices,
      neuroendocrine disorders, reproductive disorders point to close relations between
      cardiovascular and neuroendocrine systems in women with DCT.

PMID- 12181812
TI  - [Quality of life and attitude to the disease in patients with chronic gastritis].
AB  - Examination of 118 patients with various morphofunctional types of chronic
      gastritis for quality of life (QL) and personal attitude (PA) to the disease has
      revealed that in non-atrophic gastritis QL deteriorates moderately because of the
      diet, diagnostic procedures and treatment. PA is anxious, neurastenic, sensitive
      and hypochondriac; in focal atrophic gastritis QL is the same but PA is less
      negative, primarily adequate; in diffuse atrophic gastritis there are the worst
      trends in QL because of the disease, abnormal physical activity and routine life,
      PA is hypochondric, melancholic, neurastenic and egocentric. Thus, therapeutic
      policy in various morphofunctional types of chronic gastritis should account for
      personality reactions of the patients and deterioration of life quality. This
      allows maintenance of social and medical adaptation of the patients, development
      of adequate mechanisms of psychological defence, adequate treatment compliance.

PMID- 12181813
TI  - [Psychophysiological aspects of duodenal ulcer in young patients].
AB  - SMALL and Spilberg-Khanin questionnaires were used to examine psychological state
      while statistical and spectral analysis of heart rate at rest and orthostasis to
      evaluate vegetative status in 86 patients aged 15-24 years with duodenal ulcer
      (DU). Patients with mild DU had the least psychological and vegetative
      alterations primarily of the neurotic trend with a relative enhancement of the
      nervous sympathetic component. A severe disease was characterized by the greatest
      psychovegetative changes--high SMALL scales, anxiety, stress of the vegetative
      nervous systems at rest and orthostasis. Thus, alterations in psychic and
      vegetative status may serve criteria in prediction of DU course in young
      patients.

PMID- 12181814
TI  - [Urine levels of thiamine and riboflavine in diuretic therapy of patients with
      cardiovascular diseases].
AB  - Diuretic therapy entails decreased plasma concentrations of thiamine and
      riboflavine. Vitamins eliminated with urine more rapidly when diuresis
      accelerates. This process is not related to diuresis cause. A linear relationship
      exists between diuresis intensity and amount of eliminated thiamine and
      riboflavine. Thus it is shown that diuretic therapy provokes thiamine and
      riboflavine elimination from the body.

PMID- 12181815
TI  - [Practical aspects of antihypertensive therapy].

PMID- 12181816
TI  - [Work on a scientific medical article].
AB  - Motivations to writing scientific medical articles are outlined as well as types
      of medical publications and requirements to a good article. Market of medical
      papers is analysed and algorithm of search for a journal for sending publication
      is presented. Correlations between medical practice and science, training of
      personnel and co-authorship are considered.

PMID- 12181817
TI  - [Management of patients with raised and non-raised ST acute coronary syndrome].
AB  - Unstable angina pectoris has been regarded for many years as an intermediate
      state between chronic stable angina and acute myocardial infarction. Recently it
      has been found that unstable angina pectoris and myocardial infarction are
      consequences of the same pathophysiological process--rupture or erosion of
      atherosclerotic plaque and joining thrombosis and embolism of distal vessels. It
      would be valid to use the term "acute coronary syndrome" (ACS) as a provisional
      diagnosis. Among AC8 patients there are patients with and without ST segment
      elevation. This dictates therapeutic policy and predicts the patients' survival.
      Two clinical cases illustrate the validity of the above division and
      effectiveness of adequate policy of the above patients therapy.

PMID- 12181818
TI  - [Successful gastric resection in a male patient with factor VII deficiency and
      telangiectasia].

PMID- 12181819
TI  - [A benign course of histiocytosis X].
AB  - A case is reported of an accurate diagnosis of chronic histiocytosis X initiated
      with lung affection. The disease is characterized by a benign course for 7 years
      in the absence of treatment in spite of associated viral infection (hepatitis B
      virus) which is suggested to be one of causative factors of histiocytosis X.

PMID- 12181820
TI  - [Systemic lupus erythematosus and sepsis].
AB  - Features of clinical course and symptoms of systemic lupus erythematosus are
      analysed in SLE patients with sepsis (n = 11) which was defined as a systemic
      inflammatory reaction to verified infection with polyorganic insufficiency.
      Statistic analysis was made with the program MS Excel 7.0. Sepsis, activating
      factors, antibacterial and immunosuppressive therapy are discussed. Outcomes are
      described. Differential diagnosis with paraneoplastic syndrome is illustrated.

PMID- 12181821
TI  - [A case of primary hyperparathyroidism].
AB  - A case report of primary hyperparathyroidism with symptoms caused by
      hypercalcemia. Osteoporosis was detected only in thoracic spine. Test for
      parathormone provided a final diagnosis. The patient was treated surgically.

PMID- 12181822
TI  - [Differential diagnosis of neutropenia in large granulated lymphocyte syndrome
      and in rheumatoid arthritis].
AB  - The paper reports a case of leukemia from large granulated lymphocytes (LGL) in a
      patient with rheumatoid arthritis and neutropenia, describes current aspects of
      this leukemia diagnosis including morphological, immunological and molecular
      genetic methods, demonstrates other variants of neutropenia development in
      rheumatoid arthritis.

PMID- 12181823
TI  - [Disputable issues of chemotherapy and surgery in ulcer disease].

PMID- 12181824
TI  - [Problem of heart failure at XXIII European Cardiology Congress (Stockholm,
      September 2001)].

PMID- 12181826
TI  - [Endocrine function of fat tissue. Problems of obesity treatment].

PMID- 12181827
TI  - [Liposomal daunorubicin and interferon-alfa in combination with all-retinoic acid
      -a new regime for the treatment of acute promyelocytic leukemia].
AB  - AIM: To define duration and schemes of maintenance therapy, to evaluate
      cytarabine demand while treatment of acute promyelocytic leukemia (APL) with an
      original program 5D + Ifa + AT RA. MATERIAL AND METHODS: The above treatment was
      conducted in 7 patients with APL (1 male, 6 females, 18-45 years, leukocytes 1.2
      15.0 x 10(9)/l). RESULTS: Induction by 5D program was performed in 5 patients. A
      complete remission was achieved in 4 of them, molecular--in 3. One woman died. 5D
      consolidation was performed in 6 patients. After the first course of
      consolidation all the patients achieved molecular remission. Maintenance of
      remission with Ifa + ATRA was made in 5 patients. In one female the remission
      came to the end. Mean time of the follow-up was 18 months. The remission lasted 5
      36 months. Monitoring of molecular remission has not found marker PML/RARa.
      CONCLUSION: Daunozom monotherapy leads to a complete remission after the first
      course in most of the patients. In the majority of them it was molecular.
      Maintenance with If + ATRA for 2 years maintains molecular remission for 5-36
      months.

PMID- 12181828
TI  - [Clinical significance of erythrocyte ferritin in refractory anemia and chronic
      myeloid leukemia].
AB  - AIM: To find out if the RBC ferritin elevation can serve as an additional
      criterion of inefficient erythropoiesis during progression of chronic myeloid
      leukemia (CML) and in various types of refractory anemia. MATERIAL AND METHODS:
      The study group consisted of 56 MDS patients and 73 patients at various stages of
      CML. 20 healthy donors and 105 patients with verified inefficient erythropoiesis
      (20--with B12 deficiency before and after the treatment, 85--with beta
      thalassemia) were the controls. A ferritin level was measured by radioimmunoassay
      in RBC hemolysates. RESULTS: The RBC ferritin level in all types of refractory
      anemia was elevated throughout the disease course, increasing with the
      development of transfusion dependency. The CML progression was also accompanied
      by RBC ferritin level elevation associated with abnormal erythroid cell
      accumulation and elevation of intracellular PAS-positive substance (p < 0.05).
      CONCLUSION: RBC ferritin level elevation can be considered as an additional
      biochemical criterion of inefficient erythropoiesis that may be useful in
      differentiation of anemias, adequate therapy selection and follow-up of
      erythropoiesis.

PMID- 12181829
TI  - [High dose immunosuppressive therapy with autologous transplantation of stem
      blood cells in autoimmune diseases].

PMID- 12181830
TI  - [Mobilization of peripheral blood cells for auto- and allogenic transplantations
      of hemopoietic cells].
AB  - AIM: To study mobilisation of peripheral blood stem cells (PBSC) via single and
      split subcutaneous injection of granulocytic colony-stimulating factor (G-CSF)
      and isolation of PBSC concentrates for their transplantation with leukapheresis
      (LA) and large volume leukapheresis (LVL) in patients with solid tumors and
      hematological diseases as well as in the group of relative donors. MATERIAL AND
      METHODS: LA procedures were made on cell blood fractionator COBE Spectra. In
      groups 1 and 2 LVL was made with apparatus perfusion of circulating blood of the
      patient or donor (15-33 l) vs 7-12 l in LA by standard technique in group 3. To
      reduce the volume of sodium citrate solution used in LVL, to prevent citrate
      intoxication and hypervolemia, a sharp rise of anticoagulant/blood ration was
      applied. RESULTS: PBSC-mobilisation with split doses of G-CSF and large volume
      leukapheresis in 23 patients and 11 relative donors vs mobilisation in 26
      patients with single-daily dose of G-CSF and leukapheresis of 3 TBV has revealed
      that split administration of G-CSF increased the number of leukocytes and CD34+
      cells more considerably. CONCLUSION: LVL provides PBSC dose sufficient for
      transplantation during one procedure in the majority of donors and relative
      donors. This makes the method more comfortable and cost-effective.

PMID- 12181831
TI  - [Search for non-relative donor by the Russian register of bone marrow donors].
AB  - AIM: To select maximally HLA compatible donor for hematological patients who need
      transplantation of bone marrow from non-relative donor. MATERIALS AND METHODS: 75
      patients with hematological malignancy were observed. All of them have
      indications to non-relative transplantation of the bone marrow. Methods of
      polymerase chain reaction with sequence-specific primers and classic
      microlymphocytotoxic test were used. RESULTS: Typing of HLA antigens of class I
      and alleles of class II loci enabled search for non-relative donor for
      transplantation of bone marrow in accordance with the requirements of the
      European Federation of Immunogenetics. Most of the patients (86.6%) had at least
      one potential HLA-A, -B, -DR compatible donor. Half of the patients had potential
      donors typed at the allele level by class II loci. This diminishes time of HLA
      compatible donor selection. CONCLUSION: DNA typing enables the search for the non
      relative donors meeting modern requirements. This allowed 5 non-relative bone
      marrow transplantations.

PMID- 12181832
TI  - [Experience with high-dose immunosuppressive therapy followed by transplantation
      of autologous stem hematopoietic cells in patients with multiple sclerosis].
AB  - AIM: To assess efficiency of immunosuppressive therapy and subsequent autologous
      transplantation of stem blood cells (SBC) in patients with multiple sclerosis.
      MATERIAL AND METHODS: The trial enrolled 23 patients (4 men and 19 women) with
      multiple sclerosis (MS) lasting for 3 to 12 years. The age of the patients ranged
      from 18 to 44 years. The index of the progression was above 1 in all the
      patients. A remitting, primary-progredient, secondary-progredient course was
      diagnosed in 3, 3 and 17 patients, respectively. Posttransplantation follow-up
      was 1 to 1.5 years. The degree of the neurological deficiency (0-6 scores) was
      estimated by the scale of functional systems damage. Lymphocyte subpopulations
      were evaluated by enzyme immunoassay according to expression of membrane antigens
      CD3, CD4, CD8, CD16, CD20, CD25, CD56, CD95 using monoclonal antibodies ICO
      (Biomedspectr), humoral immunity--by serum levels of IgA, IgM and IgG. SBC
      mobilization was conducted for 5 days by subcutaneous introduction of neipogen
      (Roche) in a dose 8.7-10 mcg/kg. Preparation of SBC was made on Haemonetics blood
      separator on mobilization day 4-5. Cryopreservation was carried out in programmed
      freezer (Cryomed) with 7% dimethylsulphoxide as a cryoprotector.
      Pretransplantation conditioning was conducted according to the schemes BEAM +
      antilymphocytic globulin (protocol N 1) and fludar + melfalan + ALG (protocol N
      2). RESULTS: In posttransplantation period most of the patients achieved a fall
      in intensity of motor and coordination disorders. No recovery of cranial nerve
      function was observed. The protocols of pretransplantation preparation were
      compared by efficiency and organic toxicity. CONCLUSION: Indications to
      immunosuppressive therapy in MS patients were defined, pathogenetic validation of
      the immunosuppressive therapy was attempted.

PMID- 12181833
TI  - [Molecular cytogenetic monitoring of chimerism and minimal residual disease in
      patient with chronic myeloid leukemia after allogenic and syngenic bone marrow
      transplantation].
AB  - AIM: To study trends in restoration of normal and tumor hemopoiesis after
      transplantation of allogenic and syngenic hemopoietic cells. MATERIAL AND
      METHODS: The examination of bone marrow before transplantation and 1, 2, 3, 6, 9
      months, 1, 2 and 3 years after bone marrow transplantation (BMT) was made in 25
      patients with chronic myeloid leukemia (CML) after allogenic transplantation of
      the bone marrow (TBM) and 4 patients after syngenic TBM. The method of G
      differential staining of chromosomes and fluorescent hybridization in situ (FISH)
      with DNA probe to centromeric sites X/Y of chromosomes and genes BCR/ABL was
      used. RESULTS: 56% of CML patients after allogenic BMT were in cytogenetic and
      clinicohematological remission, 16% developed early cytogenetic recurrence.
      Single metaphase with t(9;22) were identified in 28%; 14.3% developed late
      cytogenetic and hematological recurrence. In patients in posttransplantation
      remission there were from 0.1 to 5.8% cells of the host. The number of cells of
      the host and the number of BCR/ABL-positive cells correlated significantly.
      CONCLUSION: The results of 8-year monitoring of chimerism and minimal residual
      disease validate application of molecular-cytogenetic methods for assessing
      transplant condition.

PMID- 12181834
TI  - [Cytomegalovirus infection in bone marrow transplantation].
AB  - AIM: To evaluate frequency and clinical features of CMV infection in patients
      with hematological malignancies (HM) after autologous and allogeneic stem cell
      transplantation, protective and therapeutic methods, efficiency of CMV
      hyperimmune immunoglobulin cytotest (Biotest Pharma). MATERIAL AND METHODS: The
      trial enrolled 22 patients (group 1) with HM and severe aplastic anemia after
      allogeneic bone marrow transplantation, 58 patients (group 2) with HM after
      autologous stem cell transplantation. The patients were examined for CMV
      infection by serologic methods and PCR. RESULTS: The probabilities of CMV
      infection were greater in group 1 than group 2--10/22(45%) versus 12/58 (21%), p
      < 0.05. Clinical signs of CMV disease were pneumonitis (27%), hepatitis (32%),
      gastroenteritis (9%), haemorrhagic cystitis (55%), slow engraftment (59%),
      prolonged thrombocytopenia (68%), encephalitis (5%). Six (60%) patients with CMV
      infection after allogeneic and 1(8%) patient with CMV infections after autologous
      stem cell transplantation were dead. The cytotest after allogeneic
      transplantation of the bone marrow reduced the risk of CMV infection from 62 to
      36%. CONCLUSION: CMV infection influences prognosis both in allogeneic and
      autologous transplantation of hemopoietic stem cells. Cytotest lowers the risk of
      CMV development after transplantation of allogeneic bone marrow.

PMID- 12181836
TI  - [Resuscitation in a hematologic clinic: urgent problems].

PMID- 12181837
TI  - [Opportunities of delayed densitometry of "late (fixed) contrast" as a test for
      tumors in residual mediastinal lesion in primary mediastinal lymphosarcoma after
      polychemotherapy].
AB  - AIM: To clarify the potential of delayed densitometry of late (fixed) contrast in
      differentiation between tumor and fibrosis in residual mediastinal lesion (RML).
      MATERIAL AND METHODS: Computed tomography (computed tomograph of the third
      generation COMATOM CR-3 made in Germany, SIEMENS) has examined 12 patients with
      mediastinal lymphosarcomas after polychemotherapy. All of them had a RML 3 to 6
      cm in diameter. RESULTS: CT has detected 8 cases of the tumor and 4 cases of
      fibrosis. The criteria of the tumor were the following: increased RML density
      shortly after the contrast medium introduction and 30 min after urographine
      introduction (p < 0.01); RML density 30 min after introduction of contrast medium
      was higher than above the aorta (p < 0.01). Fibrosis in RML was stated if RML
      density before, at the high of concentration and after introduction of the
      contrast medium was the same (p > 0.01); aortic density was significantly higher
      of RML density at the height of the contrast (p < 0.01). CONCLUSION: The above
      method differentiates the tumor with fibrosis in RML with maximal probability.
      This facilitates further choice of therapeutic policy in secondary resistant form
      of primary mediastinal lymphosarcoma.

PMID- 12181835
TI  - [Giant cell lymphosarcoma or lymphogranulomatosis variants?].

PMID- 12181839
TI  - [Plasmapheresis in combine therapy of hypercoagulation syndrome in hematogenic
      thrombophilia].
AB  - AIM: To specify indications to plasmapheresis (PA) and to assess its efficiency
      in patients with hypercoagulatory syndrome in hematogenic thrombophilia (HT).
      MATERIAL AND METHODS: 18 patients (11 males, 7 females, age 26-50 years) with
      various forms of HT received standard antiaggregation, anticoagulatory therapy
      plus therapeutic PA. By PA technique the patients were divided into two groups.
      RESULTS: A positive trend in clinical, instrumental and laboratory indices was
      observed in all the patients. CONCLUSION: Therapeutic PA in hypercoagulation
      syndrome in HT patients leads to fast normalization of the clinical picture and
      reestablishment of patency of thrombus-affected vessels.

PMID- 12181838
TI  - [Tumor necrosis factor, interleukin-6, endotoxin and procalcitonin in septic
      shock in patients with hematologic neoplasms].
AB  - AIM: To study changes in proinflammatory markers and mediators in septic shock in
      patients with hematologic malignancy (HM). MATERIAL AND METHODS: The examination
      of 33 patients with HM and septic shock included measurement of plasma
      concentrations of tumor necrosis factor (TNF), interleukine-6 (IL-6), endotoxin,
      procalcitonin (PCT) 12-24 hours before and each 12 hours after shock;
      registration of central hemodynamics parameters, the condition severity by APACHE
      II. RESULTS: Out of 33 patients 18 died of refractory shock, 15 survived the
      shock. Within the first shock hour TNF fell from 571.2 +/- 195 to 115.8 +/- 71.1
      pg/ml (p < 0.02), later being stable. In those who died and survived TNF was the
      same. IL-6 fall was seen 36 hours after shock and was observed in the survivors;
      in those who died IL-6 was unchanged. Endotoxin in the blood was detected in 21
      of 33 patients. In the survivors endotoxinemia declined after 2 days of
      treatment. 72 hours after beginning of the shock the survivors had no endotoxin.
      In shock APACH II severity of the patient's condition was graver in patients with
      endotoxinemia than without it (31.6 +/- 1.6 and 28.1 +/- 1.6 scores, p < 0.05).
      Blood endotoxin levels and APACHE II scores correlated (r = 0.24, p < 0.05)
      positively and negatively with deficiency of buffer bases (r = -0.29, p < 0.05)
      and blood pH) r = -0.3, p < 0.05), left ventricular contractility index (r = 
      0.46, p < 0.01) and right ventricle (r = -0.52, p < 0.01), mean AP (r = -0.22, p
      < 0.03). PCT concentration was lower before shock than on its hour 1 (4.2 +/- 2.9
      and 6.9 +/- 1.1 ng/ml, p < 0.05). No significant changes in PCT were found later.
      CONCLUSION: PCT is a specific marker of a severe infection. Rapid elimination
      from the blood of TNF and IL-6 makes them inadequate in sepsis diagnosis.
      Endotoxinemia aggravates the patients condition. Positive LAL-test results were
      obtained in gram-negative and fungal infections.

PMID- 12181840
TI  - [A case of unclassifiable peripheral T-cell lymphoma].

PMID- 12181841
TI  - [Mast cell leukemia].

PMID- 12181843
TI  - [Hypercoagulation syndrome: pathogenesis, diagnosis, treatment].

PMID- 12181842
TI  - [A case of atypical myelodysplastic syndrome with eosinophilia and complex
      cytogenetic changes t(3; 12)(q21; p13); t(16; 17); (q24; q12)].

PMID- 12181844
TI  - [Primary gastric lymphoma].

PMID- 12181845
TI  - [Immunological markers in histological diagnosis of lymphoma].

PMID- 12181846
TI  - The value of looking. Multiple myeloma discovered by an unusual finding in Gram
      stained spinal fluid.

PMID- 12181847
TI  - Neutropenic enterocolitis in a woman treated with 5-fluorouracil and leucovorin
      for colon carcinoma.

PMID- 12181848
TI  - Alcohol ablation of the intraventricular septum in symptomatic patients with
      hypertrophic obstructive cardiomyopathy.

PMID- 12181849
TI  - Assuring the maximum health potential of North Carolina's children. The North
      Carolina Institute of Medicine Task Force Study.

PMID- 12181850
TI  - The public health challenge of youth smoking in North Carolina. Putting what we
      know into practice.

PMID- 12181851
TI  - Speaking truth(sm) to youth. How the American Legacy Foundation is helping teens
      reject tobacco.

PMID- 12181852
TI  - The Health and Wellness Trust Fund Commission.

PMID- 12181853
TI  - Tobacco control policy-making in North Carolina for the 21st century.

PMID- 12181854
TI  - Youth speaks out. The time is now for tobacco-free schools.

PMID- 12181855
TI  - Policy options for addressing issues of youth and tobacco.

PMID- 12181856
TI  - The case for increasing North Carolina's cigarette excise tax.

PMID- 12181857
TI  - Tobacco control in the land of the golden leaf. Has political perception kept
      pace with reality?

PMID- 12181858
TI  - Access to care.

PMID- 12181859
TI  - Caught in the malpractice crossfire.

PMID- 12181860
TI  - Screening for prostate cancer.

PMID- 12181862
TI  - Thromboembolic complications of atrial myxomas.

PMID- 12181861
TI  - Atypical mycobacterial osteomyelitis in a non-AIDS patient.
AB  - Disseminated Mycobacterium avium intercellulare (MAI) infection is rare in non
      AIDS patients. We report a 60-year-old woman with chronic lung disease who
      developed vertebral osteomyelitis due to MAI. She was treated successfully with
      combined therapy consisting of rifampin, ethambutol, and clarithromycin.

PMID- 12181863
TI  - Temporal trends of risk factors associated with low birth weight--national and
      state of Connecticut: 1992-1998.
AB  - OBJECTIVES: To describe the magnitude of the problem of low birth weight in the
      U.S. and the State of Connecticut. To describe the temporal trends of selected
      risk factors associated with low birth weight (LBW) from 1992-1998. METHODS:
      Retrospective, descriptive study utilizing reports from birth certificate data
      from National Center for Health Statistics and Annual Registration Reports for
      the State of Connecticut. RESULTS: Over the seven-year period (1992-1998), the
      birth rate decreased from 15.9% to 14.6% at the national level and from 14.5% to
      13.4% in Connecticut. However, percent of low birth weight increased from 7.1% to
      7.6% at the national level and from 6.9% to 7.8% in Connecticut. There was an
      increase in the percent of premature infants nationally. Significant changes in
      the LBW risk factors at both the national level and in Connecticut were increased
      births to mothers > or = 35 years (P < 0.0001) and increased multiple births (P =
      0.0001).

PMID- 12181865
TI  - 2002 Connecticut health policymaker survey.
AB  - In Spring 2002, Connecticut health policymakers in executive and legislative
      branches of government were surveyed to assess their needs for health policy
      information and their perceptions of upcoming health challenges facing
      Connecticut citizens; a similar survey was conducted in 2000. Policymakers
      receive information from a wide variety of sources; most often from within state
      government--state agencies and legislative staff--and from health advocacy
      organizations/coalitions. The most trusted sources of information are legislative
      staff, journals/publications, and state agencies. The areas of greatest need for
      information were: health-care financing, the uninsured, prescription drug
      coverage, long-term care, and mental health/substance abuse. Between 2000 and
      2002, concerns over the costs of health care have increased significantly.
      Connecticut policymakers prefer to receive information in short, one, or two-page
      fact sheets.

PMID- 12181866
TI  - Ciprofloxacin: a warning for clinicians.

PMID- 12181867
TI  - The not so good old days.

PMID- 12181868
TI  - Hailing one of health care's priceless resources--nurses.

PMID- 12181869
TI  - A continuing dialogue: the future of nursing.

PMID- 12181870
TI  - Waiting for the days of autumn.

PMID- 12181871
TI  - Mini implants. Part I. A solution for loose dentures.

PMID- 12181873
TI  - Chronic pain management: a clinical overview.

PMID- 12181872
TI  - Impact of proton pump inhibitor utilization patterns on gastroesophageal reflux
      disease-related costs.
AB  - OBJECTIVE: To determine proton pump inhibitor (PPI) treatment patterns and their
      effect on costs related to gastroesophageal reflux disease. METHODS: This study
      used claims data to identify continuously enrolled subjects diagnosed with
      gastroesophageal reflux disease (GERD) and newly treated with a PPI between Oct.
      1, 1999 and March 31, 2000. Data were analyzed for 6 months following PPI
      initiation. Results were stratified by first PPI filled during the study period.
      Compliance (as measured by a medication-possession ratio), dosage escalation (>
      25 percent of initial dose), and daily average consumption (DACON) were measured.
      Regression analysis was performed on GERD-related costs using treatment patterns,
      type of PPI drug, and compliance as independent variables of interest. RESULTS:
      Of 75,452 subjects, there were 51,232 (67.9 percent) lansoprazole, 22,829 (30.3
      percent) omeprazole, and 1,391 (1.8 percent) rabeprazole subjects. The possession
      ratio was not significantly different by drug. Only 3.5 percent of rabeprazole
      subjects escalated versus 5.5 percent of omeprazole subjects and 9.3 percent of
      lansoprazole subjects (p = .0001). Among subjects with esophageal ulcer or hiatal
      hernia, rabeprazole users had a significantly lower final DACON (1.03) versus
      both lansoprazole (1.20) and omeprazole subjects (1.22, p = .0299). Subjects who
      were compliant with therapy (ratio > 0.80) had 43 percent higher GERD-related
      pharmacy costs and 33 percent higher GERD-related total costs (both p < .001).
      GERD-related medical costs were not significantly affected by compliance.
      Subjects who filled lansoprazole prescriptions had 9.4 percent higher GERD
      related pharmacy costs versus rabeprazole subjects (p < .01). Omeprazole subjects
      had 12.5 percent higher GERD-related total costs versus rabeprazole subjects (p <
      .01), while lansoprazole subjects had 18 percent higher GERD-related total costs
      versus rabeprazole subjects (p < .001). CONCLUSIONS: Rabeprazole subjects had
      lower GERD-related costs, less escalation, and lower DACON (measured as number of
      tablets consumed per day), compared to lansoprazole and omeprazole subjects.
      Compliance was not significantly different between the drugs, nor did increased
      compliance decrease GERD-related costs.

PMID- 12181874
TI  - The shaping of health care policy.

PMID- 12181875
TI  - The value of atypical antipsychotics in the treatment of schizophrenia.

PMID- 12181876
TI  - [Transpupillary thermotherapy in age-related macular degeneration. Preliminary
      results].
AB  - OBJECTIVE: To evaluate anatomical and functional results of transpupillary
      thermotherapy (TTT) in age-related macular degeneration (ARMD) with a chorioid
      neovascular membrane (CNVM). MATERIAL AND METHODS: TTT was performed by means of
      a diode laser (Iris Medical Oculight Six) in 38 eyes of 35 patients aged 46-93
      years, mean 70.6 years. Ocult CNVM was treated in 34 eyes, classical CNVM in 4
      eyes. In TTT we applied 1 to 5 points (on average 1.9 spot) and used a laser beam
      with a diameter of 0.5-3 mm (mean width 1.61 mm). In 10 eyes with occult CNVM
      (29%) TTT was repeated after 1-6 months. The patients were followed up after TTT
      for 6-18 months on average for 9.5 months. RESULTS: The final visual acuity (VA)
      improved after TTT in two eyes (5.3%), remained unchanged in 22 eyes (57.9%) and
      deteriorated in 14 eyes (36.8%). The mean VA after TTT declined from 0.23 to
      0.17. Biomicroscopic manifestations of exudation disappeared or receded in 29
      eyes with occult CNVM (85.3%) and in 3 eyes with classical CNVM (75%).
      Fluoroangiographic examination revealed a reduced or absent extravasation of the
      dye in 24 eyes with occult CNVM (70.5%) and in 3 eyes with classical CNVM (75%).
      Optic coherent tomography confirmed regression of exudative changes and the
      development of a chorioretinal scar in 23 eyes with occult CNVM (67.6%) and 3
      eyes with classical CNVM (75%). CONCLUSION: TTT is a new potential therapy of
      ACMD with CNVM. It is indicated in particular in occult CNVM. It can be however
      used also in classical CNVM. TTT is not economically pretentious and can be used
      also in other than large clinical departments. It is important to test the
      possibilities and limitations of TTT on a large number of patients and assess its
      position among other therapeutic procedures.

PMID- 12181877
TI  - [Results of vitrectomy in cystoid diabetic macular edema detected by optical
      coherence tomography].
AB  - PURPOSE: To evaluate the surgical results of the pars plana vitrectomy (PPV) with
      separation of the posterior hyaloid (PH) with the cystoid diabetic macular edema
      (DME) using optical coherence tomography (OCT). METHODS: PPV with removing of the
      PH was performed in 10 eyes of 10 patients with cystoid DME. The macular
      structure, the vitreoretinal interface and the foveal thickness before and after
      PPV was evaluated using OCT and was correlated with a slit lamp biomicroscope.
      All 10 eyes had undergone panretinal and macular photocoagulation. RESULTS: OCT
      demonstrated postoperatively in all 10 eyes the regression of cystoid DME and the
      presence of foveal depression. Visual acuity (VA) has improved by 2 and more
      Snellen lines in 6 eyes with preoperative decrease of VA not longer than 5
      months. CONCLUSIONS: PPV with separation of PH is efficient method in treatment
      of cystoid DME. Duration of cystoid DME is a significant factor for determination
      of functional prognosis. OCT facilitates the follow-up of the dynamics of
      regression of the structure and thickness of the fovea.

PMID- 12181878
TI  - [Long-term experience with glaucoma silicone implants in a multicenter study].
AB  - PURPOSE: To evaluate the experience with a glaucoma implant in complicated
      glaucoma, designed in collaboration with the Institute of Polymers in Prague.
      METHODS: In a multicentric retrospective study 91 eyes of 86 patients with
      otherwise uncontrollable glaucoma underwent GSI implantation in four departments.
      The implant of medical silicone consists of a tube with an internal diameter of
      0.4 mm, connected to a round lens-shaped episcleral plate 169 mm2, covering the
      tube orifice from above. The indications were infantile glaucoma (14 eyes),
      traumatic glaucoma (14 eyes), various secondary glaucomas in 12, primary open
      angle glaucoma in 11, neovascular and after PPV in 10 eyes each, usually after
      unsuccessful previous surgery. RESULTS: The average follow-up time was 20.5
      months (SD +/- 19.5). Postoperative intraocular pressure at the last control was
      6-22 mmHg in 56 eyes (50.95%). Life table analysis showed a cumulative
      probability of 494% (at least qualified success). Long-term hypotony was seen in
      6 eyes. CONCLUSIONS: The GSI is comparable with similar tube shunts but is much
      less expensive. In vitro experiments are planned to improve the construction of
      the implant and its results.

PMID- 12181880
TI  - [Malignant lymphoma of the orbit].
AB  - The authors describe a non-Hodgkin malignant large-cell B lymphoma with ample
      lymphocytes in a female patient with foci in the left breast and right orbit,
      with suspect skin foci and enlarged nodes in the mediastinum as revealed by
      computed tomography. In the differential diagnosis the authors reflected
      according to the course of the disease in addition to malignant lymphoma also on
      orbitocellulitis or a pseudotumour of the orbit. The remarkable feature is that
      the patient had already treatment on account of a multiple myeloma. The authors
      emphasize comprehensive treatment of the patient and the necessity of
      consultations with specialist of other medical disciplines associated with this
      disease. After radiotherapy total regression of the orbital finding occurred in
      the patient.

PMID- 12181879
TI  - [Detection of tumor circulating cells in patients with ocular melanoma].
AB  - The authors investigated a group of 51 patients (29 men and 22 women) with
      intraocular melanoma: 41 patients with melanoma of the chorioid, 10 patients with
      melanoma of the ciliary body. They evaluated the clinical and pathological
      finding according to the TNM classification recommended by UICC (International
      Union Against Cancer). In all investigated patients they assessed circulating
      tumour cells (melanocytes) in the peripheral blood stream based on the detection
      of mRNA tyrosinase and marker MART 1. When evaluating the presence of markers
      according to the diagnosis irrespective of time, they found in patients in the
      clinical stage of T2 choroidal melanoma a 19% positivity of different markers and
      very rare a concurrent positivity of both markers. Patients in the clinical stage
      T3 had a 51% positivity of one marker and 34% concurrent positivity of both
      markers. In melanoma of the ciliary body evidence of individual markers was
      positive in 17% and only in 11% both markers were positive concurrently. On
      comparison of therapeutic procedures from the aspect of development in time in
      patients treated by brachytherapy only rare positivity was found at the time of
      administration the radioactive plaque, following an eight-month interval after
      brachytherapy the positivity of markers increased to 28%. On evaluation of
      markers of choroidal melanoma and ciliary body melanoma resolved by enucleation
      had their positivity at the time of operation was 36%, and during check-ups up to
      one year or longer it persisted at similar levels. Concurrent presence of both
      markers before this operation was rare, during postoperative check-up
      examinations it was within a range of 23 and 33%. The presence of both markers
      was repeatedly proved in five patients with chooidal melanoma after enucleation
      of the eye, in four of them in direct correlation with a metastatic process.

PMID- 12181881
TI  - [Allergodil eye drops in the treatment of allergic conjunctivitis].
AB  - The authors describe a group of 20 patients with symptoms of allergic
      conjunctivitis where for a period of 2-6 weeks twice a day into the conjunctival
      sac of both eyes Allergidol gtt, ophth., ASTA Medica AG FRG was administered. As
      to subjective sensations the authors evaluated itching, burning, the sensation of
      a foreign body and lacrimation, as to objective signs oedema of the eyelids,
      hyperaemia of the conjunctiva and papillary hypertrophy. The authors evaluated
      also the rate of onset of the effect, its duration and tolerance of the
      preparation. Subjective symptoms disappeared in 90% patients, hyperaemia of the
      conjunctivae and papillary hypertrophy receded in 12 patients (60%), in 8 (40%)
      they disappeared. Regression of subjective complaints occurred in all patients
      within 20 minutes, the duration of the effect was within the range of 11-13 hours
      in 18 patients (90%), 6-8 hours in two patients (10%). As to undesirable effects
      one female patient reported after administration of the eye drops a bitter
      sensation in the mouth, another one a burning sensation. Evidence was provided
      that the local H1 antihistaminic Allergodil gtt is effective in monotherapy in
      mild forms of allergic conjunctivitis.

PMID- 12181882
TI  - [Optic neuritis as the first sign of multiple sclerosis].
AB  - BACKGROUND: Optic neuritis (ON) is as the initial manifestation of multiple
      sclerosis (SM) a favourable prognostic factor during the subsequent course.
      OBJECTIVE: To assess the ratio of ON at the onset of SM in the authors patients
      and to assess according to clinical criteria the form of disease and degree of
      functional inability, expressed by Kurtzke s EDSS scale. PATIENTS AND METHODS: In
      a retrospective analysis of patients with clinically defined and probable SM
      (Poser s criteria)) hospitalized at the neurological clinic in 1987-2000 the
      authors investigated the incidence of ON in relation to the course and form of
      SM. In individual patients they evaluated the age at the onset of the first
      manifestations of SM, the form, duration and degree of functional inability in
      EDSS. These findings were compared in groups of patients with incipient ON and
      without ON at the onset of SM (non-ON). RESULTS: ON as an isolated initial
      symptom of SM was present in 29 (18.2%) of the total number of 159 patients. The
      mean age at the time of the initial ON was 27.9 years which is as compared with
      the non-ON group of SM patients by 2.8 years less. Patients with isolated ON at
      the onset had the resulting general affection by 2 grades EDDSS lower than the
      non-ON and it was recorded in 73% cases with a relapse-remitting course of SM.
      The secondary progressive form of the disease accounted for 27% and the primary
      progressive form was not found. CONCLUSION: ON as the initial manifestation of SM
      is a favourable prognostic factor during the subsequent clinical course of the
      disease.

PMID- 12181883
TI  - [Refractive defects of the eye in descendents of a rural population in western
      Moravia].
AB  - The results from longitudinal follow-up of the incidence of refractive eye errors
      in a population from rural region have contributed to the characteristics of the
      regional gene pool. Generation born within 1950-1964 (Generation I.) was compared
      with that born within 1980-1994 (Generation II.). At the same time, a long-term
      follow-up has demonstrated changes in the quantity of phenotypes in absolute
      number (values of morbidity: generation I.--all types of refractive errors: urban
      population men 104/1000, women 132/1000. Rural population men 119/1000, women
      135/1000. Generation II.: urban men 132/1000, women 169/1000, rural men 124/1000,
      women 136/1000. The difference in morbidity between women and men in the Ist and
      IInd generations, both urban and rural, has not changed. A more pronounced
      difference can be seen in urban population, namely at myopia in both generations
      (myopia urban population: generation I. men 40.8%, women 59.2%, generation II.
      men 43.9%, women 56.1%, myopia rural population: generation I.: men 44.2%, women
      55.8%, generation II.: men 47.2%, women 52.8%. Hyperopia urban population:
      generation I., men 46.7%, women 53.3%, generation II. men 47.3%, women 52.7%. The
      incidence of astigmatism has shown constant ratio 1:1 both between men and women,
      and urban and rural populations. These changes were demonstrated most markedly in
      urban population, but these deviations are caused by emigration from rural to
      urban districts, especially from a hinterland. 10% of IInd generation (1980-1994)
      are relatives of Ist generation (1950-1964) only.

PMID- 12181884
TI  - [Transpupillary thermotherapy in age-related macular degeneration with choroidal
      membrane neovascularization].

PMID- 12181885
TI  - [Astigmatism after penetrating keratoplasty. I. Causes of its development].

PMID- 12181886
TI  - [Eco-environment and nutrient accumulation of sharptooth oak stands in southern
      slope of Mt. Qinling].
AB  - Based on the date from chemical analysis of 10,785 botanical and 1489 edaphic
      samples, the amount of nutrients accumulated in soil layer (0-60 cm) of
      sharptooth oak stands, the total biomass of the stands and their contents of
      accumulated nutrients, and the amount of litter and its contents of accumulated
      nutrients in southern slope of Mt. Qinling were calculated. To a certain extent,
      the biomass and the nutrient accumulation of the stands were increased with stand
      densities and stand ages from thin to high or from young to old, similar to the
      utilization efficiency of the stands to soil nutrient elements and the trunk
      canopy ratio. The tree composition of the stands much more influenced nutrient
      accumulation contents than the biomass. The more broad-leaved tree of species
      composition, the higher nutrient accumulation contents of stands. In the same
      region biomass and its nutrient contents of the stands with similar site factors
      and stand factors had not remarkably difference among different forest-types, but
      had a difference among various forest types and species composition. In different
      region, biomass and its nutrient contents of the stands with similar site factors
      and stand factors had a difference with the sequence of south slope > north
      slope, middle section > east section or west section. The utilization efficiency
      of soil nutrient elements by the stands was decreased from lower to higher
      elevation, from the south to north slope, from middle to east and west section.

PMID- 12181887
TI  - [Species structure of natural secondary forest in the Wudaohe farm].
AB  - The analysis of soil thickness and slope gradient in natural secondary forest of
      the Wudaohe forest farm showed that the area of the secondary forest whose soil
      thickness was lower than 30 cm and slope gradient was higher than 25 degrees was
      2390.1 hm2, covering 83.5% of its total area, while the area with soil thickness
      of higher than or equal to 30 cm and slope gradient of lower than or equal to 25
      degrees was only 474.2 hm2, covering 16.5% of the total. It is suggested that the
      secondary forest is ecologically fragile, and this forest farm should develop a
      mulriple forest including waterhead-protection forest, lumber stand and economic
      forest. It was shown by analytic hierarchy process (AHP) that the suitable ratio
      of three forest types is 72.7%, 18.6%, 8.7%, respectively.

PMID- 12181888
TI  - [Vegetation and its relation with climate conditions near the timberline of
      Beitai, the Xiaowutai Mts., northern China].
AB  - On the basis of field investigations, the timberline range of Beitai, the
      Xiaowutai Mountains was carved up, and the changes in the makeup and diversity of
      plants with the altitude were discussed. The results showed that the timberline
      with gradual changes in the northern slope of Beitai ranged from 2620-2800 m. In
      timberline, herbaceous plants were rich, and the diversity was higher than that
      in coniferous forest and sub-alpine meadow zones. The turnover rates of species
      were gradually hoisting from the centre of timberline to sub-alpine meadow and
      forest zones, and highest at the edge of timberline. Betula, Picea meyreri and
      Larix principis-ruprechtii species were the ecological indicator for research on
      environmental changes. Climate indication significance of these arbor species
      distributed in and near the timberline was also discussed.

PMID- 12181889
TI  - [Evaluation on degradation of Karst forest community and human disturbance].
AB  - Fire, reclamation, herd, and cut led to degradation of Karst forest in Guizhou
      Province. Five indexes as height, dominance, percentage of asexual individual,
      biomass, and percentage of shade-tolerant for evaluating community degradation
      were selected. Degraded communities were divided into six degraded grades (A-F).
      Community structure and function fluctuated normally in climax (A) under nature
      force or light human disturbance. While effect of disturbance was preponderated
      over the range of community fluctuation, climax community degraded evidently, and
      degraded degree of communities increased gradually. Degraded grades of
      communities were consistent to succession stages of degraded community. In
      degraded process, the key factor was decrease of biomass and shade-tolerant
      species. Degraded communities due to fire, herd, and reclamation were distributed
      in grades C-F, and degraded community due to cut was in grades B-C. Amount of
      asexual individual was influenced by disturbance type, and the amount in degraded
      communities due to fire and cut was more than that due to reclamation and herd.
      Degraded degree of different disturbed community was in order of cut community <
      cleared community < herded community < fired community.

PMID- 12181890
TI  - [Dynamic characteristics of nutrient elements in Castanea henryi plantation at
      beginning of fructification and its simulation].
AB  - The dynamic variation of nutrient elements in Castanea henryi plantation was
      analysed and simulated by means of a system analysis, and the models of four
      compartments including aboveground, root, soil and litter were constructed.
      Evaluation on the nutrient pools of N, P, K, Ca and Mg in the four compartments
      at the beginning of fructification showed that soil compartment had highest
      content of N, P, K and Ca which was up to 311.47, 11.64, 218.90 and 87.56 kg.hm
      2, respectively. The highest Mg occurred in litter compartment, up to 7.563 kg.hm
      2. Based on the compartment model, the fluxes and rates of the five nutrient
      elements between the compartments were calculated, and their changing trends in
      compartments in 5 years were forecasted. The results showed that the most
      suitable amount of annually compensating the five elements was 20(N), 8(P), 5(K),
      10 (Ca) and 5 (Mg) kg.hm-2, respectively. This nutrient compensation promoted the
      nutrient flows, and normalised the growth and metabolism of the tree. The
      research could provide with important basic data for nutrient management of this
      type of plantation at this stage.

PMID- 12181891
TI  - [Effect of returning corn straw into soil on soil fertility].
AB  - Three-year field micro-plot experiment was conducted to study the effect of
      applying corn root stubble, corn straw, and the ordure of cattle fed with corn
      straw to improve soil fertility in northern Liaoning province. The results showed
      that chemical fertilizers could significantly increase the corn production, while
      organic fertilizers mainly improved the soil physical and chemical properties so
      as to increase soil fertility. In comparison with no fertilizer treatment,
      combination of chemical fertilizers and organic materials could increase soil
      organic matter by 3.06%-27.78%. The increments of soil organic matter by using
      different organic materials were in order of 100% corn straw > 50% corn straw >
      mixture of cattle ordure and soil > cattle ordure > 33% corn straw > corn root
      stubble. For maintaining and increasing soil organic matter, corn straw was
      better than mixture of cattle ordure and soil, and secondly better than cattle
      ordure if they contained the same carbon content. In addition, comparing with
      applying chemical fertilizers only, combination of chemical fertilizers and
      organic materials increased soil labile oxidization organic matter by 10.91%
      20.67%, increased extractable humic acid by 1.43%-14.28%, raised slack/stable
      ratio of bonded humus by 0.07-0.19, and raised HA/FA ratio by 0.07-0.24.
      Meanwhile, this combination improved the soil nutrient status of N, P, and K, and
      the status of soil moisture and porosity, which demonstrated the increase of
      activity of soil organic matter and the improvement of soil fertility. So
      directly adding straw into soil without removing after harvest in autumn should
      be actively recommended, and the amount of corn straw added into soil should be
      30 to 50 percent of the total production of corn straw.

PMID- 12181892
TI  - [Quantification of dry matter accumulation and distribution among different
      organs of winter wheat].
AB  - Based on the field experimental data, dry matter accumulation and distribution
      among different organs of winter wheat were studied to modify the dry matter
      distribution of the winter wheat growth model. The calculating method of
      distribution and transition coefficient was introduced, and a function table
      between distribution coefficient and relative development stage was established.
      Meanwhile, the model was verified based on the experimental data, and the result
      was reasonable.

PMID- 12181893
TI  - [Effects of drought, CO2 concentration and temperature increasing on
      photosynthesis rate, evapotranspiration, and water use efficiency of spring
      wheat].
AB  - The effects of drought, CO2 concentration and temperature increasing on
      development period, photosynthesis rate (Pn), evapotranspiration (ET), and water
      use efficiency of spring wheat were investigated. The results showed that
      elevated CO2 concentration (550, 700 mumol.mol-1) could lengthen heading-ripening
      period, but high temperature (average diurnal temperature increase 4.8 degrees
      C), which made heading-ripening period shorten and speeded the seedling under
      treatment of both high CO2 concentration and high temperature, affected growing
      period more than high CO2 concentration. The combined effects of elevated CO2
      concentration and temperature enhanced Pn, stomatal resistance (r), leaf water
      use efficiency (WUEl), and whole-canopy water use efficiency (WUE), while
      transpiration rate (E) were not significantly affected. The effects on ET
      depended on soil moisture. High CO2 concentration and high temperature enhanced
      ET under high (75%-85% field water capacity) and middle (55%-65% field water
      capacity) soil moisture, but decrease ET under low soil moisture (35%-45% field
      water capacity).

PMID- 12181894
TI  - [Energy balance, water use efficiency and surface resistance in a maize field].
AB  - The characteristics of land surface/air energy translation was analysed on the
      basis of the observation data collected over a maize field in the North China
      Plain. The results indicated that the energy balance processes of land surface
      were greatly affected by the features of underlying face. Latent heat fluxes were
      the main component of land surface/air energy exchanges. Daily sensible heat
      fluxes were turned to be negative in the late growth period of maize. Among
      factors regulating surface energy translation, bulk canopy resistance was
      seasonally changed with high values in the early and late stage and with low
      value in the mid stage, and the lowest value of 25 s.m-1. This trend was closely
      related to soil cover fraction and leaf senescence condition. Water use
      efficiency (WUE) was not changed with evapotranspiration. The low WUE in the
      early stage means that the energy resources were not fully utilised, and the high
      WUE in the late stage means that enough soil water content was the key for high
      and stable yield.

PMID- 12181895
TI  - [Bioavailability of exotic zinc and cadmium in purple soil].
AB  - Correlation analysis between seven forms and available amounts (extracted by
      DTPA) of Zn and Cd, and their path analysis from soil to lettuce (Lactuca sativ
      L.) were conducted to evaluate bioavailability of zinc and cadmium and their
      contributions to the plant. The results showed that exchangeable Zn and Cd were
      significantly correlated to available Zn and Cd (r = 0.954 and 0.953) at
      significance level of 0.01, and path coefficients of exotic Zn and Cd to tissue
      Zn and Cd were 1.267 and 1.168 respectively, indicating the high bioavailability
      of exchangeable Zn and Cd in purple soil. Exotic Zn and Cd made the most
      contribution to the plant, while the path chain coefficients of CAB-Zn, MnO-Zn,
      and Cd to the plant by indirect action of exchangeable forms were 0.856, 0.592,
      0.723, respectively, showing that they may make some other contributions to
      tissue Zn and Cd through exchangeable forms. Therefore, exchangeable Zn and Cd
      are not only highest available, but also are bioavailable bridges and main paths
      from purple soil to the plant.

PMID- 12181896
TI  - [Chemical depletion of cumulative phosphorus in soils].
AB  - Cumulative phosphorus was defined as the phosphorus which was unavailable for
      plants and accumulated in soils fertilizer application. In this paper, chemical
      depletion of cumulative phosphorus in soils was studied by methods of batch
      equilibrium, kinetic, and anionic exchange resin membrane. The results showed
      that desorption amount of cumulative P increased with time increasing, and the
      desorption process was consonant with second-order kinetic equation. Release rate
      of P in different treatments was in order of PK > NPK > NK. The amount and rate
      of P released from red soil were higher than those of Fluvio-aquic soil. Desorbed
      P was significantly correlated with soil available P and P uptake by Plant. The
      maximum utilization of cumulative P in soils was about 45% of total phosphorus.

PMID- 12181897
TI  - [Dynamic tendency of arid oasis under the influence of water resources decrease-
      a case study of Ejina oasis in Heihe River Basin].
AB  - The runoff changes of arid inland river seriously influenced on the formations
      and changes of oasis in the lower reach. By the oasis patches dynamic modeling,
      the vegetation-water interrelated analysis, and the estimation of water demand by
      the ecological system, the dynamic tendency of the Ejina oasis in the lower reach
      of Heihe River Basin under difference water resources allocating were studied.
      The results showed that the lowest water demanded for preserving the present
      oasis area was about 5.7 x 10(8) m3 based on rational usage of the water
      resources. Considering the water demand of people and livestock, and the water
      lose in the water transport process, the incoming runoff through the Langxinshan
      section should be about 6.0 x 10(8) m3 to preserve the present oasis area before
      2015. To regain the oasis area to the level at the primary of 1980s, the demand
      incoming runoff should be about 8.9 x 10(8) m3, and the runoff through the
      Zhengyixia section should be 10.9 x 10(8)-13.1 x 10(8) m3.

PMID- 12181899
TI  - [Comparison of leaf tissue turnover for Leymus chinensis and Phragmites communis
      after grazing].
AB  - Leaf tissue turnover of Leymus chinensis and Phragmites communis after grazing
      was studied by application of theory and method of tissue turnover in this paper.
      The results showed that the number of living leaf of P. communis was larger than
      that of L. chinensis, but the length of living leaf of L. chinensis was larger
      than that of P. communis during the whole growth period. Both of the leaf
      appearance rate and the leaf elongation rate of L. chinensis and P. communis were
      largest at first, and then they decreased gradually. The rate of leaf wither and
      leaf senescence were in the converse trend. The leaf lifespan of P. communis was
      shorter than that of L. chinensis. The velocity of leaf tissue turnover of P.
      communis was faster than that of L. chinensis. There would be a great loss if the
      leaf tissue of L. chinensis were not used in time. The quality of grasslands
      could be improved by different utilization ways and periods.

PMID- 12181898
TI  - [Induction of sesquiterpene cyclase gene expression and antioxidant enzymes
      regulated by exongenous salicylic acid in leaves of Capsicum annuum].
AB  - An analysis of the induction of sesquiterpene cyclase gene expression and
      antioxidant enzymes in Capsicum annuum by exongenous salicyclic acid (SA) pointed
      out that the sesquiterpene cyclase gene expression in detached pepper leaves was
      induced by 0.5-4 mmol.L-1 of exongenous SA, whereas the enzyme activity and
      accumulation of cyclase mRNA were much lower, and it took a longer time (36 h)
      for the gene to be induced to express after SA treatment, comparing to other
      elicitors such as UV and fungi treatment. The activities of SOD and POD were
      enhanced, while the CAT activity was inhibited to some degree. Consequently, H2O2
      content was increased in SA treated pepper leaves. H2O2 accumulation was related
      to the integrated influences from antioxidant enzymes.

PMID- 12181900
TI  - [Effect of light on the growth and stem flowering rate of mat rush].
AB  - Stem length and whether it flowered are two key elements for mat rush quality.
      The results indicated that different photoperiod and light intensity
      significantly affected these two ones. In the early growing stage, day extension
      significantly increased stem flowering rate, lower light intensity by shading
      reduced the number of tillers, stem length, stem flowering rate and the number of
      florets per cyme. In the middle and late growing stage, shading within some
      degree could increase stem length and reduced stem flowering rate. It is
      suggested that light was one of important ecological factors to result in
      flowering transition and to affect the quality of mat rush.

PMID- 12181901
TI  - [Effects of habitat fragmentation on nesting site selection of red-crowned
      crane].
AB  - During April and May of 1985, 1995 and 1998, red-crowned crane's nesting and
      variation of breeding population quantities in Shuangtaihekou National Natural
      Reserve in Liaoning, and also the habitat fragmentation there were investigated.
      Associated with previous data of the reserve, red-crowned crane's nesting habitat
      had been seriously fragmentated into 91 patches from one integrated reed wetland.
      The area of the smallest patch was 0.37 km2, and the minimum distance of two
      nests was 304 m. Compared with records of previous data, the minimum area of
      nesting habitat reduced by 0.72 km2. However, the breeding population quantities
      of red-crowned crane had maintained at about 30 pairs for a long period. The red
      crowned crane adapted to the changed environment by the ecological adaptation
      strategy of reducing area of nesting habitat.

PMID- 12181902
TI  - [Evaluation on the impacts of environmental changes and Three-Gorge engineering
      on the population of Yangtze voles (Microtus forits) in the Dongting Lake
      region].
AB  - The relationships between the population of Yangtze voles (Microtus fortis) and
      the evolvement of the Dongting Lake beaches were analyzed based on historical
      data, and the impacts of the Three-Gorge Engineering on beach environment and
      water level of the lake were assessed according to the regulation scheme on
      downward discharge flux of the Three-Gorge dam. The results indicated that the
      population of the voles has been increasing since 1950's, owing to the continuous
      enlargement of the lake beach and prolonging successional emergence of the beach.
      The emergence date of the beach in Autumn would be earlier, its emergence area
      would be going up, the population of the voles would be also expanded at the
      initial post-construction stage, which would still increase with the continuous
      expansion of beach area in a middle and long period after the establishment of
      the dam. More voles would thus move to the farmland, and heavily harm crops.

PMID- 12181903
TI  - [Relationship between rare earth accumulation and rape sclerotiniose].
AB  - Field plot experiment with long-term application of rare earth fertilizers showed
      that 0.5-10% of adsorption capactiy and 0.6 kg.hm-2 of rare earth application had
      no remarkable effect on natural incidence of rape sclerotiniose, ratio of
      diseased plants, natural disease index, expanding rate of diseased spots, yield
      of single plant, and 1000-seed weight.

PMID- 12181904
TI  - [Relationship between population dynamic of freshwater leech Whitmania laevis and
      chemical factors of water].
AB  - The population size of freshwater leech Whitmania laevis had been observed every
      month in Guangzhou kaleyard slot from 1994 to 1998, and ten chemical factors of
      water were measured. The relationship between the population dynamic of W. laevis
      and chemical factors was studied by stepwise regression analysis method. The
      results showed that the population size dynamic of W. laevis was different every
      year. The maximum of population size appeared in April, May, and June, and the
      total population size of three months was accounted for 57.14-71.18% of whole
      year. The major chemical factors that effected on the annual population size were
      different every year, and the factors included pH value, PO(4)3-, Na+, Ca2+, and
      Mg2+. Fe3+ was the chief chemical factor effecting on population size during the
      5 years observation. The behavior of leech W. laevis was also described in this
      paper.

PMID- 12181905
TI  - [Effects of copper mine tailings on seed germination and seedling growth of five
      legumes species].
AB  - Through solution culture and soil culture experiments, effects of Tongling copper
      mine tailings on seed germination and seeding growth of five legumes species were
      studied in this paper. The results showed that the seeds of five legumes species
      could germinate in the normal and acidified tailings extracted solution, but
      germination percentage was lower than that under control. It indicated that
      tailings extracted solution had inhibition effect on seed germination, however,
      acidified tailings extracted solution promoted absorbing water of the seeds in
      early stage. In five amelioration substrates between tailings and soils, the
      tailings also inhibited seed germination of the five species. No dead seedlings
      of Glycine max, Phaseolus angularis, P. calacaratus were found within 70 days.

PMID- 12181906
TI  - [Potential of purifying SO2 of main tree species and their planting quota in
      Shenyang area].
AB  - The total potential of purifying SO2 of main tree species was studied by using
      the combination of field measurement and fumigation experiment in this paper. The
      integrated value of purifying SO2 including total bimass, absorption intensity of
      SO2, and absorption-transformation periods of sulfur by trees was 4.39 x 10(6)
      kg, which was accounted for 3.66% of total sulfur released per year in Shenyang.
      It indicated that the maximum daily potential of purifying SO2 of trees might be
      12.19 kg.km-2. Supposed that the average annual absorption capacity for sulfur of
      trees in Shenyang was 0.70 kg per tree and the average annual absorption capacity
      for sulfur of broad-leaved trees was 1.35 kg.tree-1, 88.88 million broad-leaved
      trees would be required to purify the annual released SO2 thoroughly. This number
      was equivalent to 12.9 times of existing trees. On the conditions of
      strengthening environmental protection and decreasing 20% of annual released
      sulfur, if the broad-leaved trees was double of the present number, SO2 content
      in air might be below 0.06 mg.m-3 and Shenyang would become a standardizing city
      with clear air.

PMID- 12181907
TI  - [On forest ecosystem health and its evaluation].
AB  - Definition and connotation of forest ecosystem health were introduced, and
      existing ideas and methods of health evaluation were analyzed in this paper.
      Furthermore, forest ecosystem health was discussed from the aspects of the
      management objective approach, ecosystem approach, and integration approach.
      Widespread application of ecological indicators is the main means of evaluation
      on forest ecosystem health at present, and some material forest health evaluation
      methods, especially EMAP and FHM, were introduced and summarized to impel the
      relative researches in China.

PMID- 12181908
TI  - [A review on the water physiological characteristics of Tamarix and its
      prospect].
AB  - It is very important to study and grasp the water physiological characteristics
      of Tamarix in order to use properly and scientifically manage it. Based on the
      multiply studies on the water physiological characteristics of Tamarix (P-V
      curves, predawn water potential and water potential daily course and
      transpiration rate) for many years, a preliminary comment was given on the
      experimental methods used at home and abroad. The aims of this paper is to
      understand the ecological characteristics of Tamarix as fast as possible and
      provide theoretical bases for the restoration and re-establishment of Tamarix in
      the arid and semi-arid region.

PMID- 12181909
TI  - [Spatial heterogeneity and forest regeneration].
AB  - The research on spatial heterogeneity is meaningful for forest regeneration
      dynamics, which is a critical part in the forest ecosystem dynamics.
      Traditionally, forestry scientists are mainly concentrated their attention to the
      studies on the process of regeneration. However forests are spatiotemporal
      heterogeneous. In regeneration, there exists an ecological dynamic process at
      temporal scale, but also a heterogeneous pattern at spatial scale. Almost of the
      factors influencing forest regeneration, including both botic and abotic
      environment, both natural and human disturbances, and both characteristics of
      tree species and response of tree species to different disturbance agents, are
      spatially heterogeneous. Discussion on spatial heterogeneity and its effect on
      regeneration is indispensable for the understanding of the pattern, process and
      mechanism of forest regeneration. Main research contents and viewpoints of
      spatial heterogeneity in forest regeneration were summarised on the basis of
      available literature, and sources of spatial heterogeneity in the process of
      regeneration were analysed. The response of species to spatial heterogeneity,
      small-scale spatial heterogeneity and regeneration dynamics, spatial
      heterogeneity of lights in stand and regeneration pattern, and correlative
      relationships between the scales of soil heterogeneity and regeneration
      heterogeneity were reviewed.

PMID- 12181910
TI  - [Advances in the ecological risk management of pollution point sources of
      toxicants in aquatic environment].
AB  - Progress in this field in developed countries and China was reviewed and the
      prospects were also presented in this paper. Based on the water quality standards
      and discharge standards, the chemical-specific approach in common use could not
      effectively control complex discharges containing toxic organics. Therefore,
      applying this traditional approach only was not a valuable measure. Toxicity
      based approach could be used at the same time to supply the gap for the control
      of complex discharges containing toxic organics effectively based on the
      requirements of ecological risk management. Toxicity identification evaluation
      (TIE) for identifying the key toxicants causing the effluent ecotoxicity was a
      core of the ecological risk management of point sources of toxics. The prospects
      were also described for the development of TIE methodology and the application of
      toxicity-based approach to the ecological risk management of point sources of
      toxicants in aquatic environment in China.

PMID- 12181911
TI  - [Advances of studies on ecological risk of herbicide atrazine and its
      determination and remediation].
AB  - With wide application of chemical such as pesticide in farming, the coming
      problems of ecological risks and environmental pollution were increasingly
      serious. Residual material of atrazine was founded in the surface water,
      underground water, and atmospheric sedimentation, and it resulted in the global
      ecological influences. For atrazine could exit in soil for a long time and enrich
      in organism, it would bring about potential threaten on the safety of food. The
      results from experiments on animal indicated that atrazine had biological
      activity. So, there is an increasing demand for further studying on its
      ecological risks. In this paper, some viewpoints of the researches on atrazine
      were introduced. With the development of analytical techniques, the opportunities
      were created to study on the ecological risks of atrazine, and people should
      attach serious importance to the bioremediation techniques.

PMID- 12181912
TI  - [Application of continuous-flow culture in microecological research].
AB  - The application of continuous-flow culture in microbial ecology and its advances
      were reviewed. Continuous-flow culture can be used to build in vitro models
      simulating ecosystems composed of normal bacteria such as human or animals
      intestinal and buccal bacteria, to examine the interactions between normal
      bacteria and pathogens, to investigate the physiological and biochemical traits
      of bacteria and their metabolic products, and to develop microecological
      preparations.

PMID- 12181913
TI  - [Establishment and applications of the spatial database of land resources
      information in Anshun, Guizhou Province].
AB  - For the purpose of managing and processing land resources and environment
      information, a spatial database of land information in Anshun City, Guizhou
      Province, which involved present data and the investigated information by remote
      sensing, was established under the supporting of PAMAP GIS 4.2. The spatial
      database could provide the functionality of querying for spatial data and its
      associated attributes, conversion between the different data formats, mapping the
      digital terrain, fast and accurate analysis on soil resources, land assessment
      and management application, and soil erosion risk mapping. The establishment of
      this spatial database was expected to play an important role in territorial
      planning, agricultural sustainable development, spatial assessment of ecological
      environment, and so on.

PMID- 12181914
TI  - [Benefit of sediment reduction by biological measures in the watershed scale].
AB  - Based on the measured data and the model of plotted watershed hydrology, the
      benefit of sediment reduction by biological harnesses of soil and water
      conservation was studied in the watershed scale. The result indicated that the
      erosion modulus in Wangdonggou watershed, which were 1869 t.km-2, 1050 t.km-2,
      383 t.km-2, and 504 t.km-2 in the periods of the sixth, seventh, eighth, and
      ninth five-year plans, respectively, were gradually reduced by comprehensive
      measures. Taken out the effect of rainfall, the sediment reduction by biological
      measures of soil and water conservation was increased by 24.1% and 22.4% in the
      periods of eighth and ninth five-year plans compared to that in the seventh five
      year plan.

PMID- 12181915
TI  - [Effect of agrochemicals and bio-control productions on soil nematode community
      dynamics].
AB  - Dynamics of soil nematode communities amended with agrochemicals and bio-control
      preparations were investigated in a soybean field. The results showed that the
      frequency of plant non-parasitic nematodes were obviously higher in soil amended
      with bio-control preparations (Doufeng 1) than with urea and herbicide, however,
      that of plant parasitic nematodes exhibited an inverse trend.

PMID- 12181916
TI  - Recruitment and retention of nurses in residential aged care.

PMID- 12181917
TI  - [Fairness of health care].

PMID- 12181918
TI  - [Screening of breast cancer].

PMID- 12181919
TI  - [Examination and therapy of a painful breast].

PMID- 12181920
TI  - [Outcome of surgical treatment of colorectal cancer in Mikkeli Central Hospital].

PMID- 12181921
TI  - [Embolization therapy of severe obstetric hemorrhage in connection to labor].

PMID- 12181922
TI  - ["Mini Medical School"--the basics of medicine in an open university].

PMID- 12181923
TI  - [A bruise in the back].

PMID- 12181924
TI  - [Viktor Jansson: Ready (A fighter)].

PMID- 12181925
TI  - [When is an andrologist needed?].

PMID- 12181926
TI  - [I am a man--or am I?].

PMID- 12181927
TI  - [Male biology--is the man only testosterone?].

PMID- 12181928
TI  - [Male sexual dysfunction].

PMID- 12181929
TI  - [Andropause].

PMID- 12181930
TI  - [Drugs and the masculinity].

PMID- 12181931
TI  - [MS patients should get beta-interferon therapy early and for a long time].

PMID- 12181932
TI  - [Advantages of female sterilization--is there disadvantages?].

PMID- 12181933
TI  - [Cranial and facial anomalies].

PMID- 12181934
TI  - [Aspergillosis in stem cell transplant recipients].

PMID- 12181935
TI  - [Blood culture positive Staphylococcus aureus infections in children].

PMID- 12181936
TI  - [Myocardial infarction triggered by grief reaction].

PMID- 12181937
TI  - [ECG changes, resembling anterior myocardial infarction, caused by spontaneous
      pneumothorax].

PMID- 12181938
TI  - [Maintenance of insulin treatment].

PMID- 12181939
TI  - [Einar Ilmoni: A sick woman].

PMID- 12181940
TI  - [Abdominal problems in an old lady].

PMID- 12181941
TI  - Nutritional support of the patient receiving high-dose therapy with hematopoietic
      stem cell support.
AB  - Hematopoietic stem cell transplantation (HSCT) is an intensive therapy that is
      being used increasingly in an attempt to cure certain malignancies. One of the
      major adverse effects of this treatment is an inadequate oral intake that may
      result in dehydration and malnutrition. Factors that may contribute to inadequate
      oral intake include mucositis, nausea, vomiting, and anorexia. In addition, prior
      to transplant, many patients may have experienced, or continue to experience
      malnutrition associated with malignancy and its therapy. Traditionally, total
      parenteral nutrition (TPN) has been the mainstay of nutritional support in this
      patient population. The blood and marrow transplant (BMT) team at the Ottawa
      Hospital has significantly decreased the use of TPN through the initiation of a
      comprehensive nutritional support program that uses a variety of interventions
      including oral supplementation and enteral feeding. Understanding the causes and
      implications of malnutrition, and using tools that allow risk assessment and
      timely implementation of appropriate nutritional interventions, may facilitate
      full patient recovery parallel to hematopoietic recovery in the HSCT patient
      population.

PMID- 12181942
TI  - The use of unconventional therapies among cancer patients: implications for
      nursing practice.
AB  - This essay received an honourable mention in the 2001 Canadian Cancer Society's
      essay contest for oncology or cancer control (nursing program). The complexity of
      human experience in relation to illness requires that nurses and physicians be
      knowledgeable of available treatment modalities. Historically, the health care
      system has been based on the medical model (Burk, 1998). However, cancer patients
      are using complementary and alternative therapies at increasing rates nowadays.
      Given that there has been an increase in the use of unconventional therapies
      internationally, it is apparent that this is of great significance for the
      practice of nursing, and demands adequate consideration by nurses throughout the
      world. The purpose of this paper is to outline and discuss the views and
      arguments pertaining to whether or not cancer patients should be informed about
      alternative and complementary therapies by nurses, and to explore what can be
      done to influence resolution of this debate. The format of this paper is as
      follows: first, a brief description of alternative and complementary therapies
      and my position on this issue; second, a description of the contexts shaping this
      issue; third, a description of the stakeholders in this issue; fourth, an
      identification of assumptions and beliefs shaping this issue; and fifth, the
      position that nursing groups have taken on this issue.

PMID- 12181943
TI  - Canadian strategy for cancer control: governance and implementation workshop.

PMID- 12181944
TI  - The 2001 Helene Hudson Memorial Lecture. The power of story: using intimacy and
      love in oncology nursing practice.

PMID- 12181945
TI  - Evidence-based practice: implications for the practising oncology nurse.
AB  - While the premises of EBP seem highly appropriate on the surface, disquieting
      questions are raised when one examines the implications for the practising
      oncology nurse of attempting to implement EBP. There are clinical situations for
      which no empirical evidence exists on which to base nursing decisions. In some
      cases, empirical evidence is sparse and based on a mix of small, descriptive
      studies. Although guidelines exist for examining purely quantitative literature
      and are being developed for examining purely qualitative literature, no
      guidelines exist for evaluating a mixture. The process of operationalizing EBP is
      time-consuming and requires expertise which many oncology nurses lack. Does this
      mean that EBP is a laudable but impossible enterprise? I don't think so. Nurses
      will need to incorporate the empirical literature as well as other sources of
      knowledge to inform their clinical decision-making. In addition, oncology nurses
      need to apply and adapt models, such as Howell and Pelton's (2001), to make the
      best use of all sources of knowledge to facilitate excellent patient care.

PMID- 12181946
TI  - Oncology nurses' experiences regarding patients' use of complementary and
      alternative therapies.
AB  - In their search for information and in making decisions about complementary and
      alternative therapies, patients will turn to oncology nurses. How oncology nurses
      respond to the patient's questions or comments can have an impact on the decision
      a patient makes about pursuing a particular therapy or whether the patient feels
      supported. The impetus for this work was the desire to understand how oncology
      nurses are responding to the patient trend of using complementary and alternative
      therapies. Twenty-eight nurses were interviewed over the telephone and a content
      analysis was completed from the transcribed interviews. The nurses who
      participated in this study regularly engaged in conversations with patients about
      complementary therapies and were aware of the reasons patients pursued these
      therapies. Conversations about alternative therapies occurred less frequently,
      but often created turmoil for the nurse. The nurses thought they had a role in
      maintaining an open dialogue about therapies, but felt their knowledge about
      particular therapies was limited. Obtaining information was a challenge and they
      often learned about specific therapies from patients and the popular media.
      Turmoil arose for nurses most often with regards to patients pursuing ingested
      therapies or alternative therapies. Nurses suggested complementary therapies to
      patients, but usually waited for patients to raise the topic of alternative
      therapies. Providing support to patients, whatever course they are choosing to
      pursue, was seen as an important nursing role.

PMID- 12181947
TI  - Enhancing palliative care through Watson's carative factors.
AB  - Palliative care is aimed at alleviating the suffering of patients with terminal
      illnesses. As more patients make the decision to die at home, community
      palliative care has become an alternative to hospitalization. The literature was
      examined in relation to the needs of terminally ill patients in the community and
      their families to determine their priority needs. Patients were found to have
      physical, psychosocial, and spiritual needs, while families had needs in relation
      to the physical care of their loved ones, as well as information and psychosocial
      needs. The use of Watson's theory of human caring, and in particular her carative
      factors, was found to be an appropriate nursing model to direct palliative care
      nurses in meeting the needs of both patients and their families.

PMID- 12181948
TI  - The 2001 Schering Lecture. Listening with more than your stethoscope: feeling
      with more than your fingertips: advanced practice nursing in oncology.

PMID- 12181949
TI  - [Cell replacement and stem cell therapies are coming].

PMID- 12181950
TI  - [Neural transplantations in the management of neurological diseases].

PMID- 12181952
TI  - [Adaptation to a near person's suicide].

PMID- 12181951
TI  - [Neuroborreliosis].

PMID- 12181953
TI  - [Efficacy of organized screening in comparison to spontaneous Pap samples in the
      prevention of invasive cervical cancer].

PMID- 12181954
TI  - [A relief from neural pain--gabapentin helped against hip ache in a girl with
      cerebral palsy].

PMID- 12181955
TI  - [Prevention and treatment of traveller's diarrhea].

PMID- 12181956
TI  - [A painful lump in the thigh].

PMID- 12181957
TI  - [Hard to find evidence on efficacy of radiotherapy in musculoskeletal pain
      syndromes].

PMID- 12181958
TI  - [Homemaker and physician].

PMID- 12181959
TI  - [Type 2 diabetes can be prevented by life style changes].

PMID- 12181960
TI  - [Expensive pharmacological prevention of atherosclerosis].

PMID- 12181961
TI  - [Breast conserving surgery for mammary cancer].

PMID- 12181962
TI  - [Reference values of the oscillometric technique give support to asthma
      diagnostics in small children].

PMID- 12181963
TI  - [Human cowpox--a new zoonosis in Finland].

PMID- 12181964
TI  - [Prosthetic valve thrombosis].

PMID- 12181965
TI  - [Follow-up of patients with brain tumor].

PMID- 12181966
TI  - [Hard and acute headache in an elderly person].

PMID- 12181967
TI  - [Iivari Honkola: The country wedding].

PMID- 12181968
TI  - [Adolescent and substance abuse].

PMID- 12181969
TI  - [The nature and course of substance use disorders in adolescents].

PMID- 12181970
TI  - [Treatment of substance-related disorders in adolescents].

PMID- 12181971
TI  - [Indications for involuntary treatment of an adolescent with substance use
      disorder].

PMID- 12181972
TI  - [Will TIA go over?].

PMID- 12181973
TI  - [Are children in the shadow region of drug therapy].

PMID- 12181974
TI  - [Some light for the prognosis of gastric cancer].

PMID- 12181975
TI  - [Gene errors of dilated cardiomyopathy].

PMID- 12181976
TI  - [Hypoalbuminemia and its clinical significance].

PMID- 12181977
TI  - [Surgical management of glaucoma is still needed].

PMID- 12181978
TI  - [Diagnostics of Smith-Lemli-Opitz syndrome with the help of gas chromatography].

PMID- 12181979
TI  - [Lung volume reduction procedure in the treatment of severe emphysema].

PMID- 12181980
TI  - [Surgical management of respiratory insufficiency due to diaphragmatic
      paralysis].

PMID- 12181981
TI  - [Ventricular fibrillation--a life-threatening complication of cardioversion].

PMID- 12181982
TI  - [Gout].

PMID- 12181983
TI  - [A food loving child with rhinitis].

PMID- 12181984
TI  - [Does the patient have strength enough, and does the physician?].

PMID- 12181985
TI  - [Subtle changes of meanings].

PMID- 12181986
TI  - [Is the goal to increase the level of doctoral candidates or the level of
      science?].

PMID- 12181987
TI  - [Direct endoscopic approach improves prognosis of septic-synovitis in the horse].
AB  - The medical records of 71 horses with sepic arthritis, bursitis, or
      tenosynovitis, treated between 1996 and 2001 at Dierenkliniek Enmeloord, were
      reviewed. A total number of 81 joints, tendon sheaths and bursae were treated (21
      tarsi, 17 digital tendon sheaths, 14 metacarpo/metatarso-phalangeal joints, 12
      stifles, 6 carpi, 4 coffin joints, 2 navicular bursae, 1 elbow joint, 1 proximal
      interphalangeal joint, 1 tarsal sheath, 1 bursa calcanei subtendineum). The
      aetiology in 42 cases was a penetrating wound (group 1), in 4 cases an intra
      articular injection, and in 2 cases arthroscopic surgery (group II), and in 13
      cases septic arthritis in young foals (group III); in 10 cases the aetiology was
      unknown (group V). A total of 93 endoscopic lavages was performed on 81 joints,
      tendon sheaths, and bursae (1-3 lavages, mean 1.18 lavage per synovial
      structure). Survival rates were 95% for group I, 100% for group II, 73% for group
      III and 100% for group IV. Horses were discharged after 4-73 days of
      hospitalization (mean 20 days). Longterm follow-up revealed a survival rate of
      92% for group I, 100% for group II, 67% for group III, and 90% for group IV. Of
      the surviving horses, 89% were sound and 11% had some degree of residual
      lameness. It is concluded that instant aggressive treatment using endoscopic
      techniques yields the best results so far and is therefore recommended.

PMID- 12181988
TI  - [A special case of intestinal torsion in a cow].

PMID- 12181989
TI  - [Dachshund and Co].

PMID- 12181990
TI  - [Reaction to the news article about anesthetic weapons].

PMID- 12181992
TI  - [Predecessors: veterinarians from earlier times (48). Heinrich Albert Johne (1839
      1910)].

PMID- 12181993
TI  - [The consequences of the surgery decision (health and welfare law for animals)
      for certain physical surgeries in horses].

PMID- 12181994
TI  - Executive coaching: employing trusted advisors to improve performance.

PMID- 12181995
TI  - The trusted advisor: "pinnacle relationships" with executive coaches.

PMID- 12181996
TI  - Should the executive coaching process be invisible?

PMID- 12181997
TI  - [Effect of variable magnetic field on motor impairment and quality of life in
      patients with multiple sclerosis].
AB  - Modern treatment of multiple sclerosis (SM) takes into consideration the current
      stage of the disease, symptomatic treatment and modification of the course of the
      disease. The most promising method of management is immunotherapy. It is,
      however, effective only in some cases, in patients with low degree of disability,
      and it is rather expensive. In view of some recent reports concerning the
      possibility of utilisation of variable magnetic fields in the treatment of SM,
      the study was undertaken to evaluate the effectiveness of impulses generated by
      magnetic field obtained by means of VIOFOR JPS stimulator. The study was carried
      out on 76 subjects with long-term history of clinically confirmed SM. The mean
      duration of the disease was 8.5 years, and the mean age of the patients 37.8
      years. The patients were divided into two groups: the study group and the
      controls. In the study group the patients were exposed to magnetic fields
      generated by VIOFOR JPS. Magnetic stimulation was not applied in the control
      group. The progress of the disease according to EDDS and the quality of life
      according to Testa and Simonson Questionnaire were assessed on admission and
      after 21 days of stimulation. No significant differences between the groups were
      found with respect to motor impairment evaluated using the EDDS score (6.2 at the
      beginning of the study and 5.1 after 21 days; in the control group--6.1 and 5.6,
      respectively). The quality of life was found to be significantly better in the
      group exposed to magnetic field stimulation than in the controls (p < 0.01).
      Particular variables contributing to the physical, psychological and social
      component of quality of life were analysed in detail. The most significant
      difference was observed with respect to the improvement of mental condition of
      the patients (alleviation of depression, elimination of anxiety, better emotional
      control), as well as to the decrease of muscle tone, dysaesthesia and painful
      sensations. No side effects were observed in any of the cases. The obtained
      effects encourage us to recommend magnetic stimulation as a method supplementing
      symptomatic treatment of patients with multiple sclerosis.

PMID- 12181998
TI  - [Malignant thyroid lymphoma--diagnostic and treatment problems].
AB  - The aim of this study was to present our experience in the diagnostics and
      treatment of primary malignant thyroid lymphoma (PMTL). Five patients at the age
      of 48-72 years with PMTL were treated at the Department of General Surgery in
      Bytom in the years 1988-1999. They made up 0.04% of patients operated on at this
      time in our Department because of different types of goiter and 1.05% because of
      thyroid carcinoma. The clinical examinations included ultrasonography,
      radioisotope diagnostics, preoperative thin needle biopsy and hormonal
      examination of thyroid gland. All patients were operated on under general
      anesthesia and with intraoperative histopathological examination. They were
      treated with chemo- and/or radiotherapy in postoperative period. The appearance
      of PMTL was preceded by nodular goiter or Hashimoto disease. In three cases we
      observed neck compression symptoms and in two the dramatic course of disease.
      Ultrasonography revealed hypoechogenic thyroid gland with nodular structures
      characterized by the decreased J131 uptake. In one case thin needle biopsy
      confirmed the diagnosis of PMTL. Evident hypothyreosis was diagnosed in one and
      subclinical in two patients. Surgical treatment--partial excision of neoplastic
      tumor--was complicated by tracheostomy in two cases. One case with almost total
      resection of thyroid gland was complicated by lesion of esophagus which was
      sutured. After operation one patient was treated with chemotherapy, one with
      radiotherapy and two cases using both of methods. Three patients died: in 3rd,
      32nd day and after 3 months since surgery. We confirmed the remission of the
      disease in two the youngest patients with not advanced state. One of them was
      treated with Co 60 therapy and the second one with chemotherapy according to COP
      and radiotherapy. CONCLUSIONS: PMTL is a rare disease and difficult to diagnose.
      The biopsy is useful. The treatment of PMTL combined, including surgical
      treatment, chemo- and radiotherapy. The prognosis is uncertain and depends on the
      disease period.

PMID- 12181999
TI  - [Profile of microorganisms isolated in nasopharyngeal swabs from the patients
      with acute infectious mononucleosis].
AB  - Infectious mononucleosis is a self-limiting lymphoproliferative disorder, which
      contribute to the development of the various clinical symptoms. Exudative
      tonsillitis was found to be caused by Epstein-Barr virus in 19% of all viral
      infections and may imitate a bacterial etiology. The aim of this study was to
      identify the microbes from the nasopharyngeal swabs obtained from the patients
      with exudative tonsillitis and to assess their susceptibility to antibiotics. The
      patients were hospitalized as an infectious mononucleosis after unsuccessful
      antibiotic therapy. 84 patients were investigated: group I--patients with
      serological positive infectious mononucleosis tests and group II--patients with
      acute exudative tonsillitis and with serologically excluded infectious
      mononucleosis. The diagnosis was confirmed clinically, haematologically,
      biochemically and serologically. Nasopharyngeal specimens were taken, once, at
      the first day of hospitalization. Then, routine microbiological assays were
      performed. Isolated strains were identified biochemically: API Strep, API Staph,
      API E, API Ne, APINH (bioMerieux). The susceptibility to antibiotics with an agar
      diffusion assay was performed according to Kirby-Bauer. We concluded that
      various, potentially pathogenic bacterial flora was found in throat during
      infectious mononucleosis. Haemophilus spp. and Staphylococcus aureus MSSA were
      isolated more frequently. Haemophilus influence was susceptible to cefotaxime and
      azytromycine. Candida albicans was isolated in every fourth patient.
      Streptococcus pyogenes as an etiological agent of exudative tonsillitis was
      confirmed in the group II. The pharyngeal candidiosis was also observed more
      frequently in the group II.

PMID- 12182000
TI  - [Antibodies seroprevalence for mycoplasma pneumoniae antigens in patients with
      bronchial asthma].
AB  - Microorganisms causing respiratory system infections, mainly viruses but also
      bacteria, among which there are atypical such as Chlamydophila pneumoniae, play a
      role in etiopathogenesis of bronchial asthma. Mycoplasma pneumoniae is suggested
      to take part in the initiation and the bronchial asthma exacerbation. The aim of
      the paper was to determine the frequency of occurrence of anti-Mycoplasma
      pneumoniae antibodies in serum of patients suffering from bronchial asthma in
      comparison with the control group of healthy persons. The presence of IgG, IgM
      and IgA class anti-Mycoplasma pneumoniae antibodies was assessed by
      immunoenzymatic assay ELISA. Serologic markers of Mycoplasma pneumoniae infection
      were more frequently observed in patients with bronchial asthma (15%) than in the
      control group (5.13%). The diagnosis of Mycoplasma pneumoniae infection is
      especially important in patients with bronchial asthma. The pathogen causing
      bronchial hyperreactivity is eliminated by the appropriate antibiotic therapy,
      which allows reducing the dose of inhaled corticosteroids. The immunoenzymatic
      assay determining the level and class of specific antibodies to find
      mycoplasmatic infection quickly and precisely.

PMID- 12182002
TI  - [Estimation of the influence of psychological support on body mass reduction in
      the obese patients].
AB  - Obesity is an excessive accumulation of fatty tissue in the organism. Incorrect
      eating habits and low physical activity are the major cause of overweight and
      obesity. The aim of the study was to investigate the efficiency of dietetic
      treatment and increased physical activity in patients with excessive body mass.
      The study was carried out on 140 patients with overweight or simple obesity (131
      women and 9 men), aged 15-65 years, the members of the support group previously
      instructed in dietetics. The treatment consisted of the application of diet 1000
      1500 kcal/day and the participation in the programme of body-mass reducing
      exercises (physical exercise twice a week and exercise in water once a week for
      45 min). The attendance was monitored and those who missed the classes were
      excluded from the group. The study was terminated after 2 years. In the group I
      (exercising for 0-3 months) 39 patients reduced their body mass by 7.7 kg on the
      average. In the group II (exercising for 3-6 months) 59 patients reduced their
      body mass by the average of 14.5 kg. In the group III (exercising for 6-12
      months) in 38 patients the average loss of body mass was 20.9 kg. In the group IV
      (exercising for over 12 months) 4 patients reduced their weight by 26-70 kg (mean
      50 kg), which gave the 26.5-47% loss of the initial body mass. The patients with
      overweight and obesity included in the present study reduced their body mass
      through the application of an adequately selected diet and increased physical
      activity. More than 40% of the patients were able to preserve up to 6 months of
      the programme, and about 30% up to one year.

PMID- 12182001
TI  - [Echocardiographic assessment of circulation system in patients during and 3-5
      years after all therapy in childhood].
AB  - Circulatory disturbances may occur during and after the treatment of acute
      lymphoblastic leukemia (ALL). The reasons are: leukemic infiltrations of the
      heart, anaemia, renal disturbances, infections, cardiotoxic drugs, especially
      anthracyclines (Atc). The aim of the study was echocardiographic assessment of
      circulatory system in patients during and 3-5 years after ALL therapy in
      childhood. The study group (group B) consisted of 20 children, aged 1-16 years,
      who underwent Atc treatment with cumulative doses 155.8-330 mg/m2 and
      cardioprotective agent--dexrazoxane. In this group echocardiography was performed
      before the treatment as well as after 1, 6, 12 months and 3 years. The
      retrospective group (R) consisted of 36 persons aged 12-24 years, examined 3-5
      years after the completion of ALL treatment, who had undergone the treatment with
      Atc in doses 148.6-416.7 mg/m2 without cardioprotection. The control group (K)
      consisted of 28 healthy volunteers, aged 9-25 years. In all subjects
      echocardiography was performed, standard measurements taken, systolic and
      diastolic indices of left ventricle (LV) function calculated. In patients during
      and 3-5 years after the treatment neither LV dilatation nor abnormal wall
      thickness was found. The systolic indices remained normal. In the group B
      echocardiographic indices did not change significantly during 3 years of
      treatment and did not correlate with growing cumulative Atc doses. In this group
      isovolumetric relaxation time (IVRT) was significantly longer, what emphasized
      the need of further clinical and echocardiographic follow-up.

PMID- 12182003
TI  - [Blood flow in ophthalmic artery and visual evoked potentials in diabetic
      patients].
AB  - Diabetes despite the progress in therapy causes various complications including
      the visual impairment. The evaluation of Visual Evoked Potentials (VEP) gives the
      possibility to detect subclinical features of visual tract damage whereas
      Transcranial Doppler Sonography enables non-invasive vessel assessment including
      Ophthalmic Artery (OA). The assessment of VEP and Blood Flow Velocities (BFV) of
      carotid and ophthalmic artery in diabetics with various changes in retinal
      arteries was the purpose of this investigation. 26 diabetics, at the average age
      of 43.7 +/- 12.1 years and average diabetes treatment duration of 9.4 +/- 4.9
      years, and 43 healthy controls were examined. In each patient ophthalmoscopy,
      doppler examination of carotid and ophthalmic arteries (CCA, ICA, ECA, OA) and
      evaluation of VEP was performed. BFV of ICA and ECA was significantly greater (p
      < 0.001) whereas BFV of OA was greater in diabetics in comparison to the
      controls. VEP latency was significantly prolonged (p < 0.01) in diabetic patients
      compared to control group. BFV of ICA and OA in retinopathy patients was
      significantly lower comparing to angiopathy patients (p < or = 0.02; p < or =
      0.01 respectively) whereas VEP amplitude was similar in examined subgroups of
      diabetics. The correlation between BFV of OA and VEP latency was not observed in
      diabetics. The obtained results suggest that diabetes affects negatively blood
      flow velocities of important for visual organ vessels as well as visual tract
      conduction.

PMID- 12182004
TI  - [Dynamics of the changes of blood and plasma rheological properties in ischaemic
      stroke].
AB  - The aim of the study was to establish relation between hemorheological
      disturbances and the degree of pathological changes in patients with ischaemic
      cerebral stroke as well as to examine the dynamics of changes in blood and plasma
      viscosity during hospitalization and treatment. The patients were divided into
      two groups according to ischaemic changes extent recognized on the basis of
      tomogram and clinical examination: group I--ten patients at the age of 64 +/-
      11.8 years with hemiparesis and with hypodense cerebral foci several mm in
      diameter; group II--eight patients at the age of 65 +/- 10 years with hemiplegia
      and more severe course of disease. The hypodense foci in the brain were several
      centimetres Blood viscosity measurements were carried out by Brookfild's
      viscometer using cone-plate system and plasma viscosity by Ubbelohd's capillary
      viscometer at the temperature of 37 degrees C. Apart from rheological
      examinations, blood morphological measurements, ESR and biochemical examinations,
      such as sugar blood concentration, total cholesterol, LDL cholesterol, HDL
      cholesterol, triglycerides and total serum proteins were performed. It was found
      that in patients in the group II both viscosity of whole blood and plasma as well
      as corrected viscosity were significantly higher. What is more, degree of
      rheological disturbances of blood and plasma was related to severity of the
      course of the disease. Observation of the dynamics of changes in rheological
      parameters showed that rheological parameters of blood and plasma during
      hospitalization and treatment improved along with recovery.

PMID- 12182005
TI  - [The complications of the use of hemodialysis catheters in central veins of the
      upper part of body--own experience].
AB  - Catheters with the double lumen are commonly used in order to obtain the
      temporary access to circulation enabling hemodialysis in patients with renal
      failure. The placement of catheter in the central vein is not entirely safe
      procedure. Instead it involves the number of complications connected with both
      the insertion of catheter and leaving it in the vessel for a longer time. In 66
      patients with renal failure the authors have analysed those complications which
      accompanied the catheterization of central veins. In those patients the temporary
      access to circulation was obtained by the puncture of jugular internal or
      subclavian vein. There were 21 men in the examined group at the age of 40-77
      years (61 on average) and 45 women at the age of 26-78 years (57 on average). The
      obtained results were statistically analysed. It turned out that the
      complications appeared in 23 cases which was 36.4% of the examined group. The
      most frequent complications were infections (35%), thrombotic changes in the
      catheter lumen (35%) and haematoma or bleeding (21%). The incidence of infection,
      thrombotic changes and bleeding in the place of catheter insertion was similar in
      each of applied central accesses. However, the incidence of bleeding in the place
      of the insertion of catheter was significantly higher in patients with
      coagulation disorders.

PMID- 12182006
TI  - [Nedocromil sodium--the influence on allergic inflammation].
AB  - Asthma is an inflammatory disease of airways which is associated with airway
      hyperresponsiveness clinically manifested by diurnal variations of peak
      expiratory flow (PEF), impaired lung function and recurrent symptoms. The
      specific role of mast cells--the key effector cells involved in the inflammation
      occurring in milder forms of the disease is discussed. According to the GINA
      guidelines inhaled nedocromil sodium is one of the medications recommended as the
      preferred choice in the treatment of mild persistent asthma. There is also
      opinion that nedocromil sodium (NS) plays a role as an early therapeutic
      intervention. Recent data suggest its efficiency in the controlling the symptoms
      of a mild asthma. NS has been shown to inhibit the immediate release of mediators
      from mast cells and sensory nerve activation. NS blocks chloride channels
      involved in cell activation and in this mechanism it may influence inflammatory
      cells and consequently inhibit, bronchospasm, cough and wheezing. As it is known,
      nedocromil sodium can reverse the clinical features of airway inflammation in
      asthma. It decreases the severity of symptoms, diurnal variation of PEF,
      bronchial hyper responsiveness as well as improves pulmonary function.

PMID- 12182007
TI  - [Skin lesions in renal transplant recipients].
AB  - Renal transplantation is considered the only good long-term therapy for chronic
      renal failure. Better surgical techniques and recent advances in
      immunosuppressive therapy allow patients to survive for many years, free from any
      complications due to rejection. However, cutaneous lesions can be a significant
      problem for this group of patients. Immunosuppression predisposes them to
      infections--predominantly viral, but also fungal and bacterial ones, as well as
      malignant tumours like basal cell carcinoma, squamous cell carcinoma, melanoma
      and Kaposi's sarcoma. The review of the current literature on skin manifestations
      in renal transplant recipients is done.

PMID- 12182008
TI  - [The process of moulding knowledge about illness in patients with ischaemic heart
      disease].
AB  - The presented work handles the problem of the process of moulding knowledge about
      illness on the example of cardiologic patients. The papers cognitive frames are
      pointed out by the conception of transfer of knowledge. The author acknowledges
      that the patients convictions and behaviours can be understood more thoroughly if
      the following aspects are analysed: doctors convictions and attitudes, their
      skills in transferring the medical knowledge (to the patients) and ability to
      recognize the capacities and limitations of patients. Considering social changes,
      we can respect the gradual evolution of the present models of relations between
      patients and medical staff to the forms closer to the recommended ones.

PMID- 12182010
TI  - [A case of Wegener's granulomatosis].
AB  - We present a case of Wegener's granulomatosis in which otitis media symptoms
      masked the disease in first phases. Progressive, unilateral hearing loss, almost
      deafness, together with facial nerve paresis allowed us to make proper diagnosis
      and apply therapy.

PMID- 12182009
TI  - [Myelosis funicularis as a result of secondary vitamin B12 deficiency in a 9-year
      old girl].
AB  - A nine-year-old girl without aggravating family history or adverse pregnancy and
      neonatal outcome, who underwent a resection of the end section of the small bowel
      as a result of atresia in the first twenty four hours of her life, was admitted
      to the Department on account of spastic paresis of the lower extremities. Apathy
      and tiredness appeared the most striking features on the physical examination of
      the child; likewise the pale colour of skin and a scar on the abdomen integuments
      -a result of the resection. Neurological examination revealed pyramidal syndrome
      from the lower extremities, disturbed sense of balance with intensified with
      closed eyes, and deep sensibility disorders. Megaloblastic anaemia was revealed
      on further examination, while bone marrow image showed normoblastic
      erythropoiesis with the presence of megaloid cells. The extremely low level of
      vitamin B12 in the blood serum and a regular level of folic acid were found. The
      vitamin B12 absorption test (Schilling test) showed considerable impairment in
      the process. The inflammation of the esophagus and duodenum mucosa was confirmed
      in a histopathological examination. Furthermore, irregular result of
      somatosensory induced potentials (SEP) and conductivity test revealed some
      characteristics of axonal--demyelinating neuropathy in the lower extremities. MRI
      of the head and spinal cord was correct. The diagnostics excluded methylomalonic
      acidosis, multiple sclerosis and other causes of ataxia in children. The overall
      clinical picture, that is megaloblastic anaemia, the characteristics of the
      myelosis funicularis and interview data--resection of the bowel as well as other
      examinations confirmed that the observed disorders resulted from the impairment
      of vitamin B12 absorption. An appropriate treatment consisted of supplementation
      of vitamin B12 (intramuscular) and folic acid (orally) improved the neurological
      condition and hematologic parameters. CONCLUSIONS: It is necessary to monitor
      hematologic parameters and the neurologic condition in the group of children who
      underwent the resection of the ileum in infancy. If vitamin B12 deficiency
      symptoms occur, appropriate treatment should be duly applied.

PMID- 12182011
TI  - [Metachronous tumor of the small intestine--rare cause of ileus in a patient
      after resection of colon cancer].
AB  - Neoplastic metastases in the small intestine are rare--only 2% of the metastases
      are localized in the small intestine. It is important to remember that colorectal
      metastases are the most frequent, though metachronous cancer of the small
      intestine is the rare cause of ileus or bleeding in patients who underwent
      resection of the colorectal cancer. The challenge is to select among those
      patients, the ones with metachronous tumor in the other parts of the small and
      large bowel. The diagnostics in these situations is often difficult and only the
      operative management is an optimal way of treatment. We present the case of the
      patient with metachronous cancer of the small intestine after the sigmoid
      resection and the diagnostic difficulties concerned.

PMID- 12182012
TI  - Gonarthritis in the course of Lyme disease in a one-and-a-half-year-old child.
AB  - A case of a one-and-a-half-year-old girl is reported in whom gonarthritis in the
      course of Lyme disease was diagnosed. The girl was brought up in an urban
      environment. She never was in a forest and had no contact with animals (except
      for a healthy pet-dog, which was under veterinary supervision). She did not
      attend a nursery, and went for walks only within urban area under the careful
      guidance of her parents. In spite of the negative family history the level of
      antibodies against Borrelia burgdorferi was estimated. A very high level of IgG
      antibodies and a low level of IgM Borrelia burgdorferi antibodies, accompanied by
      physical symptoms allowed to diagnose the second stage of Lyme disease. We
      considered the described case as worth presentation due to the child's very early
      age. Moreover, the infection was caused supposedly due to the contact with a dog
      (which may be unusual carrier of ticks), and not--as in most cases--in a forest.

PMID- 12182013
TI  - [Epidemiology of thyroid cancer in Poland].
AB  - The aim of the paper is to analyse the epidemiological situation of thyroid
      cancer in Cracow region from 1986 to 1999 and to review regional thyroid cancer
      registers in Poland (including 43.7% of the Polish population) in 1999. The
      standardized register was based upon assumptions: 100% of histopathological
      verification according to ICD-10, the register ascertainment in at least 80%, the
      demographic area not smaller than 100,000 inhabitants, the incidence rate (IR)
      calculated as the newly diagnosed cases number per 100,000 inhabitants in a
      calendar year. Since 1990 a statistically significant rise of the thyroid cancer
      incidence affecting mainly women > 40 years of age have been observed. From 1998
      1999 the cancer morbidity was reduced. Within the last 5 years in the Cracow area
      the follicular carcinoma incidence has decreased significantly, which has been
      associated with effective iodine prophylaxis. The highest incidence values have
      been observed in Cracow and Olsztyn, showing a territorial relationship with the
      highest thyroid irradiation doses after Chernobyl accident. The mean IR value has
      been 3.86 (1.48 men, 6.08 women), which corresponds to about 1500 newly diagnosed
      cases in Poland in 1999. The follicular to papillary carcinoma ratio has been
      5.32. The major etiological factors have been iodine deficiency and ionising
      radiation. The present data have indicated that iodine prophylaxis should be
      continued and that the population should be protected against ionising radiation.

PMID- 12182014
TI  - [Occurrence of papillary and follicular thyroid cancer among Silesian women].
AB  - In the years 1990-2000 within Silesia District 1067 thyroid cancer cases were
      diagnosed. From the total, papillary carcinoma established 59.9% (639 cases), and
      follicular carcinoma--26.0% (276 cases). An existence of some distinct endemic
      areas--for both papillary and follicular thyroid cancers simultaneously was
      confirmed. The etiologic background is unclear, but the significant impact of
      environmental iodine supply seems unprobable.

PMID- 12182015
TI  - [The role of fine needle biopsy in diagnosis of thyroid cancer].
AB  - The majority of changes in the structure and consistency of the thyroid gland is
      a clear indication for fine needle aspiration biopsy (FNAB). This does not mean,
      however, that cytological evaluation provides an unequivocal diagnostic
      confirmation for every pathological change found by palpation or by imaging
      technology. The main purpose of FNAB is to differentiate the type of examined
      pathological lesion (i.e. neoplastic or non-neoplastic) and to help in the
      selection of appropriate therapy. The diagnoses obtained by FNAB may be divided
      into five categories. FNAB plays the key role in the diagnostics of papillary and
      anaplastic thyroid carcinoma.

PMID- 12182016
TI  - [Evaluation of thyroid cancer morbidity in Warsaw in 1987-1997].
AB  - The crude and standardized thyroid cancer incidence rates calculated for the
      period 1987-1997 in Poland increased from 0.5 to 0.9 and 0.5 to 0.8 per 100,000
      men, and from 1.8 to 3.6 and 1.4 to 2.8 per 100,000 women. The incidence of the
      cancer in women in Warsaw doubled during the same period. The upward trend only
      slightly showed up in the male population of Warsaw. Mortality rates caused by
      the thyroid cancer in both sexes in Warsaw population declined over the years
      1963-1997. The 5-year relative survival rates, calculated for the period 1985
      1989, were lower in men than in women (respectively 66 and 49%). This fact can be
      partly explained by more frequent occurrence of anaplastic tumours in men than in
      women (respectively 14.2 and 7.8%).

PMID- 12182017
TI  - [Thyroid cancer morbidity in the Olsztyn region in 1993-1999].
AB  - Olsztyn region (in the north of Poland) was classified as an iodine deficiency
      area with moderate endemic goiter prevalence. Following Chernobyl accident, the
      population had one of the highest radiation doses affecting thyroid. Aims of the
      study were to estimate the incidence of thyroid cancer and to determine its
      histopathological type. The register was carried out in Olsztyn region population
      including each newly diagnosed case of thyroid cancer in the calendar year. The
      personal data of patients were collected and processed on in computer. The
      incidence rate was calculated as the number of newly diagnosed cases in the
      calendar year per 100,000 inhabitants dependent on sex and age. The results were
      statistically evaluated. 242 newly diagnosed cases of thyroid cancer were
      registered including 8 young patients (up to 18 years of age) and 234 adults. The
      increase in the number of cancer cases was observed year by year. The predominant
      type of thyroid cancer was papillary carcinoma--66.8%. Follicular carcinoma
      constituted 17% of cases. A statistically significant increase of incidence rate
      was observed in women--from 2.8/100,000 to 11.1/100,000.

PMID- 12182018
TI  - [Incidence of thyroid cancer in children and adolescents in Bialorus after the
      Chernobyl catastrophe in 1986].
AB  - Fifteen years after Chernobyl nuclear plant catastrophe thyroid cancer was
      diagnosed in 882 persons among the group of 2,618,482 persons aged 6-18 years.
      The radioactive contamination, mainly with isotopes of radioactive iodine, seems
      to be a major cause of such a high incidence of thyroid cancer in children and
      adolescents. However, it is necessary to consider other factors which also might
      influence the process of transformation of the thyroid cells to the thyroid
      cancer. The iodine deficiency in environment was recognized as an important
      factor. Therefore, the countrywide programme of the investigations of iodine
      deficiency and goiter prevalence was established in the Republic of Belarus with
      the assistance of WHO Office for Europe. Within this program the examination of
      11,562 children and adolescents aged 6-18 years from 30 schools in urban and
      rural areas was performed. The results obtained are typical for significant
      iodine deficiency and moderate goiter endemy. The analysis of these two factors
      and their influence on the incidence and distribution of thyroid cancer in
      different regions of Belarus is a subject of this paper. It is worth adding that
      15 years after the catastrophe a visible rise in the number of thyroid cancers is
      noted in the group of adolescents and adults.

PMID- 12182019
TI  - [Ionizing radiation as a risk factor for thyroid cancer in Krakow and Nowy Sacz
      regions].
AB  - In a group of 224 patients with thyroid cancer registered from 1990 to 1999 and
      in 243 controls matched for sex and age doses for the thyroid due to accumulation
      of 131I after Chernobyl accident and radiological diagnostic procedures involving
      the neck and dentition was calculated according to Johnson's model and based upon
      questionnaires. There was a significantly higher dose for the thyroid due to
      accumulation of 131I in the Krakow area in comparison with the Nowy Sacz area.
      There was also a significantly higher frequency of radiological procedures
      involving the thyroid gland preceding the development of thyroid cancer in
      comparison with the control group. The present findings are concordant with about
      40% increase of thyroid cancer in the Krakow area in comparison with the Nowy
      Sacz region. The present study has indicated that ionising radiation may be a
      factor involved in the pathogenesis of thyroid cancer and its significant rise
      within the last 10 years. However, it has not been the main factor, but only one
      of the risk factors. The study has also indicated that iodine prophylaxis should
      be continued and that radiological procedures involving the neck and head in
      patients with nodular goitre should be carried out with caution.

PMID- 12182020
TI  - [Biological risk factors for differentiated thyroid cancer].
AB  - Apart from the two relatively well documented risk factors for thyroid cancer
      i.e. iodine deficiency and ionising radiation, the mechanism of carcinogenesis
      involves a number of biological and environmental factors. The aim of the study
      was to analyse the selected biological and environmental risk factors in patients
      with differentiated thyroid cancer in comparison with a reference group in a case
      control study. METHODS: Both the group of 188 women and 30 men with thyroid
      cancer including 92 with follicular carcinoma and 126 with papillary carcinoma
      and the control group of 287 women and 58 men were subjected to the examination.
      All the study participants were given a standard questionnaire and underwent
      physical examination including thyroid USG, blood hormone levels and urine iodine
      concentration. The following risk factors were included in the analysis: family
      history, sex, age, thyroid morbidity, employment, body weight, hormone
      replacement therapy in women, cigarette smoking. In both groups with thyroid
      cancer women predominant with the female to male ratio 6.7 in follicular
      carcinoma and 6.0 in the papillary variant. In both groups of diagnoses the mean
      age was high--above 50, higher in men than in women. Over 70% of the patients
      with thyroid cancer had nodular goitre before the detection of cancer. In the
      control group the proportion of diagnosed goitre was slightly above 10%. A
      significantly more frequent hormone replacement therapy and contraception and
      more frequent miscarriages in women with thyroid cancer were noteworthy. One may
      assume that initiation, promotion and progression of the neoplastic process in
      the thyroid is triggered by a number of factors, both biological and
      environmental, and only multifactorial analysis may provide an insight into the
      mechanisms of carcinogenesis followed by initiation of preventives measures in
      appropriate cases.

PMID- 12182021
TI  - [Iodine deficiency and thyroid neoplasms in the Krakow region].
AB  - The aim of the study was to evaluate the correlation between incidence rate (IR)
      of thyroid cancer and severity of iodine deficiency. The influence of iodine
      prophylaxis on IR was also investigated. The suspension of iodine prophylaxis in
      1980 resulted in goitre prevalence increase in schoolchildren (up to 60%) and
      elevated TSH levels in neonates observed in early 1990-ties. In 1990 rise in
      thyroid cancer IR was observed. IR of papillary and follicular carcinoma in 1995
      were 1.6 and 1.5 respectively. Papillary to follicular ratio was about 1.0. Such
      a high prevalence of follicular cancer was specific for iodine deficient regions.
      In 1997, after introduction of mandatory model of iodine prophylaxis in Poland,
      increase in papillary thyroid cancer IR was observed, reaching in 1998 6.23 per
      100,000 inhabitants. Papillary to follicular cancer ratio rose to 2.48. In 1999
      no further increase in thyroid cancer IR was observed. Increase in papillary
      cancer incidence between 1990 and 1999 may be related to overlapping of iodine
      deficiency and other cancer risk factors i.e. radiation after Chernobyl accident.

PMID- 12182022
TI  - [Geographic differences in iodine supply in the Silesia terrain in relation to
      thyroid cancer risk].
AB  - Risk factors associated with differentiated thyroid carcinoma depend on its
      histotype. Follicular carcinoma is described as a predominant type in the areas
      with iodine deficiency, in opposite to papillary thyroid cancer. The incidence of
      thyroid cancer and its histotypes varies considerably throughout Silesia (data
      obtained from the Institute of Oncology Cancer Register, Gliwice). The factors
      responsible for these differences are unknown. The aim of our study was to
      evaluate the present iodine supply in Silesia region and to relate it to the
      incidence of the various histotypes of thyroid carcinoma. Urinary iodine
      excretion observed in 7-11 year-old-children was used as a parameter of iodine
      supply and measured in the group of 1037 school children in sixteen localities,
      equally dispersed throughout Silesia. Urine samples were obtained to measure
      iodine concentration by the modified Sandell-Kolthoff's catalytic method. Mean
      incidence rates of papillary and follicular thyroid carcinoma were calculated for
      regions of Silesia by averaging the rates of the communities in each region.
      Despite the intensive iodine prophylaxis the persistent symptoms of iodine
      deficiency were observed. There were significant differences in children's
      ioduria among investigated regions. The percentage of low ioduria (lower then 100
      micrograms/l) varied from 35.7% to 87.7%. We observed no correlation between age
      adjusted rates for histotypes of thyroid carcinoma and the percentage of urine
      iodine below 100 micrograms/l, which served as an estimation of iodine
      deficiency. Our study indicates that Silesia is still an area of moderate iodine
      deficiency. We were unable to explain the factors responsible for the observed
      differences in the incidence rates of papillary and follicular thyroid carcinoma.

PMID- 12182023
TI  - [Evaluation of surgical treatment results in patients with differentiated thyroid
      cancer from materials in the Oncologic Institute in Gliwice].
AB  - The optimal surgical treatment for patients with differentiated thyroid carcinoma
      is still controversial and discussed. The aim of this study was to analyze the
      effectiveness of treatment in differentiated thyroid carcinoma, to establish the
      prognostic value of histopathological type, clinical advancement, the extent of
      surgery and to estimate the therapeutic benefit rate of the radical approach. The
      randomized group of 768 patients with differentiated thyroid carcinoma, aged
      between 16 to 40 (median age 44), treated in Oncology Center Institute in Gliwice
      between 1986 and 1997 were analyzed. They were operated in different surgical
      clinics in Poland. The primary total thyroidectomy was performed in 153 of
      patients (20%), the secondary radical operation in 474 (62%). 136 persons were
      operated by less radical approach. Cervical lymph node metastases were observed
      in 26% of patients. Distant metastases occurred in 8% of cases. 610 persons were
      treated with 131I. All patients were administered hormonal therapy to suppress
      TSH. Locoregional recurrence occurred in 7.5% of patients. Complete remission was
      observed in 71.5% of persons (548 patients). The influence of distant metastases
      lymph node metastases and tumor size on the long-term prognosis was analyzed in
      univariate statistic analysis. There were no differences in survival in patients
      with papillary and follicular carcinoma. The 10-year survival was statistically
      significantly longer in patients who underwent radical surgical treatment (92%)
      than after non-total thyroidectomy (80%). Despite the relatively high risk of
      surgical complications the benefits of the radical approach were significant.

PMID- 12182024
TI  - [Radical surgical treatment of differentiated thyroid cancer--necessity or over
      enthusiasm?].
AB  - The extent of surgical treatment of well differentiated thyroid cancer has been
      controversial and widely discussed for years. Although the recommendations
      defining the strategy of thyroid surgery were approved in 1995, a lot of
      questions remained. The aim of this retrospective study was to analyse long-term
      results of surgical treatment of thyroid cancer according to the type of applied
      surgical procedure. The study group consisted of 206 patients surgically treated
      for well differentiated thyroid cancer with the minimal follow-up period of 5
      years. The median age patients was 49.1 years. 159 patients (77.2%) have still
      remained in the follow-up programme, 23 died because of thyroid cancer (11.1%)
      and the remaining 24 have either refused to participate in the programme or died
      of other causes. Median follow-up period was 10.7 years. Total thyroidectomy was
      performed in 90 patients (43.7%) and less extensive procedures in 106 (51.4%).
      The remaining patients were qualified for palliative reduction of the tumour mass
      and they were not included in this study. The comparison of the patients with I
      and II stage of the disease according to the type of surgical procedure did not
      show differences in 10-year survival. In stage III the difference was very close
      to statistical significance. The same results were observed with regard to
      disease recurrence. Long-time survival in low risk patients was not related to
      the extent of surgical procedure. The risk of recurrence and death was higher in
      the patients with advanced disease in stage III who underwent less radical
      procedures like total resection of involved lobe with isthmus and subtotal
      resection of contralateral lobe.

PMID- 12182025
TI  - [Cervical lymph node surgery in differentiated thyroid cancer: selective or
      elective lymphadenectomy?].
AB  - The value and prognostic significance of regional lymph node dissection in
      patients with thyroid cancer remains a matter of controversy. The classification
      of the cervical lymph nodes and the extent of their resection in patients with
      different thyroid cancers is also discussed. The aim of the paper was to present
      the space classification of regional lymph nodes, the incidence of their
      involvement and the extent of their resection in patients with differentiated
      thyroid cancer. The results of multicenter studies have indicated that regional
      lymph node metastases in patients with differentiated thyroid cancer, especially
      of a papillary type, have been frequent. Ipsilateral central, ipsilateral
      lateral, contralateral lateral, and mediastinal lymph nodes have been affected in
      42-86%, 32-68%, 12-24%, and 3-20% of patients respectively. In 20% of patients
      only central lymph nodes have been affected, whereas in others metastases have
      been determined at least in 2 or more lymph node groups. Regional lymph nodes
      have been classified into Groups I-IV. Moreover, lymph node recurrences have been
      more frequent in patients who either have not got the regional lymph nodes
      removed or have only enlarged ones determined as involved excised. Therefore,
      primary regional lymph nodes dissection is indicated. Elective resection of the
      lymph nodes of Group I (central lymph nodes) as a part of primary total
      thyroidectomy in patients with thyroid cancer and more selective excision of the
      lymph nodes of Groups II-IV are recommended. The author has presented his own
      experience in lymph node dissection in patients with differentiated thyroid
      cancer and compared it with other results.

PMID- 12182026
TI  - [Should cervical lymph nodes be electively removed in differentiated thyroid
      carcinoma?].
AB  - Differentiated thyroid carcinomas (DTC; papillary and follicular) constitute
      merely 0.5-1% of all malignancies in the world. The proper extent of their
      surgical resection has been discussed for many years. Two different approaches
      predominate in the literature. One group claims, that elective, modified radical
      neck dissection (MRND) should be performed. That strategy is supported by high
      frequency (80%) of observed "occult", clinically not evident, micrometastases in
      regional lymph nodes on the neck. On the other hand, there have been no studies
      so far which would unquestionably confirm the prognostic value of neck lymph node
      involvement in DTC, or the favorable influence of elective lymph node dissection
      on long-term survival. Therefore, other authors do not recommend prophylactic
      lateral neck dissection. MRND, apart from its doubtful influence on prognosis, is
      connected with a higher complication rate and longer hospitalization. The authors
      of this review also share this opinion.

PMID- 12182027
TI  - [Current views on diagnostic standards and treatments with L-thyroxine of single
      non-toxic thyroid nodules or multinodular non-toxic goiter].
AB  - The present opinions on the therapy with L-thyroxine (L-T4) of single non-toxic
      thyroid nodules, as well as of multinodular non-toxic goitre are rather
      divergent. This treatment is based on the suppression of TSH secretion from the
      pituitary. There are no doubts that FNAB performance is the first and--at the
      same time--the most significant diagnostic procedure in the case of thyroid
      structural lesions (nodules, goitre, thyroiditis). FNAB performance should--by
      all means--precede the beginning of L-T4 application for the treatment of thyroid
      nodules. The simplicity, clearness and high efficacy, with comparable results in
      each case, are the core of good diagnostic algorithm. Unfortunately, non all
      diagnostic algorithms concerning thyroid nodules and multinodular goiter, fulfill
      these important criteria.

PMID- 12182028
TI  - [Early evaluation of results after total thyroidectomy in patients with thyroid
      cancer].
AB  - 219 patients (159 females, 60 males) operated in Clinic of Oncological Surgery in
      Gliwice between 1995 and 1999 were analyzed in this study. In 89% of cases
      differentiated thyroid carcinoma (DTC) was diagnosed. In other patients medullary
      cancer (8%) and anaplastic one (3%) were diagnosed. Total thyroidectomy with
      removal of the central cervical lymph nodes compartment was performed in all
      cases. In 86% of operations bilateral nodal biopsy was done. In 27% of cases
      modified cervical lymph node dissection was performed. 44 patients were in T4
      stage. In 51% of cases cervical nodal metastases were observed. The operation was
      estimated as radical in 195 patients. Distant metastases occurred in 15 patients.
      Bilateral paresis of recurrent laryngeal nerve was not observed, unilateral was
      noticed in 8.7% of cases, permanent hypoparathyroidism appeared in 15% of
      patients. In postoperative scintigraphy radioiodine uptake was in the range of 0
      10% in 206 cases and in the range of 0-3% in 2/3 of operated patients. 125
      patients with DTC were treated with 131I. All patients with DTC were administered
      L-thyroxine to suppress TSH. In other types of cancer substitutive hormone
      therapy was introduced. In the entire group 8 deaths occurred and 13 cases of
      local recurrences were observed during the observation. CONCLUSION: The results
      prove the high effectiveness of the radical thyroidectomy performed in thyroid
      cancer.

PMID- 12182029
TI  - [Evaluation of results after repeated radical surgery for differentiated thyroid
      cancer].
AB  - Total thyroidectomy is the treatment of choice in thyroid cancer. Unfortunately,
      the diagnosis is not always established before the first operation and the
      secondary radical surgery is necessary. The aim of this study was to analyze the
      effectiveness of secondary surgery in differentiated thyroid carcinoma. The
      randomized group of 768 patients with differentiated thyroid carcinoma, treated
      in Oncology Center Institute in Gilwice between 1986 and 1997 was analyzed. Among
      them 474 persons (56%) - 398 females and 76 males (median age 44 years) were
      operated more than once in different clinics in Poland. They were compared with
      136 persons operated by less radical approach. Negative histobiological risk
      factors were noted in 4% to 33% of cases. Cervical lymph node metastases were
      observed in 18% of patients. Distant metastases occurred in 3% of cases. 373
      persons were treated with 131(I). All patients administered hormonal therapy to
      suppress TSH. After secondary operation the rate of cancer foci was 28% (when
      radicalization was performed durning one year after primary surgery) and 56% when
      it was done later. This difference was statistically significant (p=0,0002).
      Locoregional recurrence was observed in 5% of patients. In the entire examined
      group the actual 5-year-survival was 98% and 10-year-survival was 92%. Complete
      remission was observed in 80% of patients. The incidence of multifocality in 1/3
      of cases and the presence of neoplasm in the re-operated thyroid gland in 1/4 of
      cases have substantiated the decision for secondary surgery. The delay in
      radicalization surgery of more than 12 months has doubled the risk of
      multifocality in thyroid gland remnants. Our results have confirmed the necessity
      of the secondary surgery after nonradical primary thyroid resection in
      differentiated thyroid carcinoma.

PMID- 12182031
TI  - [Problems associated with general anesthesia in patients with thyroid cancer].
AB  - The group of 100 patients with thyroid cancer operated in Institute of Oncology
      in Gliwice was described. The risk of anaesthesia, intraoperative complications
      and the results obtained depend on the preoperative preparation, especially on
      adequate treatment of endocrine disorders of thyroid, parathyroid and adrenal
      glands. It is necessary to estimate the presence of multiendocrine disorders in
      medullary thyroid carcinoma, especially of those with pheochromocytoma, because
      of its high mortality in the non alfa-blockers prepared patients.

PMID- 12182030
TI  - [Clinical picture of differentiated thyroid carcinoma in the T1 stage].
AB  - Patients with thyroid microcarcinoma have usually excellent prognosis. However,
      recurrences in neck and distant metastases have been reported. The optimal
      treatment for this group of patients is still discussed. The aim of study was to
      present the clinical and histopathological data of our group of patients with
      differentiated thyroid carcinoma of 1 cm or less in size diagnosed from 1990 to
      2000. 146 patients (137 females and 9 males, mean age 47 years) with
      differentiated thyroid carcinoma up to 1 cm in the greatest dimension were
      analyzed. The median follow-up time was 3.5 years. The diagnosis was incidental
      (made after primary surgery) in 82% of cases. In 85% of patients papillary
      thyroid carcinoma was diagnosed (in 6% of them as follicular variant).
      Histopathological risk factors were noticed in 32 patients (21%). The patients
      were operated in different surgical clinics in Poland. 5% (8) of primary
      operations and 51% (33) of secondary ones were performed in our center. The most
      frequent primary operation was bilateral, subtotal strumectomy (62%). Total
      thyroidectomy was made in 14% of cases (21). Secondary radical operation was
      performed in 65 patients (44%). Residual cancer was found in 9% of reoperated
      patients. 47% of patients (69) were treated with 131I and all of them were
      administered hormonal therapy to suppress TSH. No recurrence and distant
      metastases were observed. Lymph node metastases were diagnosed and treated in 10
      patients (7%). During observation period 1 patient died because of breast cancer.
      No statistically significant influence of clinical and histopathological risk
      factors or operation type on clinical outcome was observed. In the analyzed group
      secondary surgery was connected with the higher risk of complications.
      CONCLUSIONS: In thyroid papillary microcarcinoma total thyroidectomy is
      recommended for patients with multiple foci of neoplasm or with metastases (lymph
      node or distant). Establishment of optimal treatment in minimal follicular
      thyroid cancer is not possible on the basis of our data and published literature.

PMID- 12182032
TI  - [Significance of intraoperative isotope detection in primary and secondary
      radical surgical treatment of thyroid cancer].
AB  - When diagnosis of the thyroid carcinoma is made preoperatively, total
      thyroidectomy with excision of lymph nodes involved in neoplastic process is
      indicated. The cases of carcinoma diagnosed upon tissue examination after
      strumectomy performed for other indications should be referred for radical
      rethyroidectomy. Even after macroscopically total thyroidectomy, postoperative
      scintigraphy may reveal remnants of thyroid tissue, the most often in the place
      of pyramidal lobe, in proximity of the laryngeal recurrent nerves or small
      metastatic lymph nodes overlooked during the first operation. In order to improve
      the rate of surgical cure, intraoperative scintigraphy was performed.
      Intraoperative evaluation of totality of the operation was performed in 114
      patients. In all cases postoperative scintigraphy revealed iodine uptake above 1%
      (ranging from 1.9% to 23%). The other group of 186 patients had the radicalness
      of total thyroidectomy and total rethyroidectomy checked intraoperatively with
      gamma-beams detector. Radioiodine uptake ranged postoperatively in these patients
      from 0% to 3.74%. Only 73 (39%) of them required radioiodine treatment due to
      iodine uptake above the neck. The intraoperative use of gamma-beams detector
      allows improving totality of thyroidectomy and for significant reduction in
      number of patients who require ablation with radioiodine.

PMID- 12182033
TI  - [Possibilities and limitations of intraoperative isotope detection for thyroid
      carcinoma].
AB  - Intraoperative probes become increasingly important in the surgical management of
      cancer. Attempts with gamma probe guided surgery to improve the completeness of
      surgical excision of radioiodine avid tissues in thyroid cancer have been
      performed through several decades. The first Polish results by Pomorski et al.
      have shown that gamma probe guided surgery after preoperative dose of 131I have
      allowed locating and increasing the completeness of thyroid excision. These
      results have been substantiated by other authors. However, in the evaluation of
      intraoperative gamma probe localization of 131I avid tissues one should remember
      of the limitations of the method. The article begins with a discussion of the
      statistical limitations of the radiation detection and of the key performance
      parameters that characterize detectors. Later on we continue with the description
      of specific aspects concerning gamma probe guided surgery in thyroid cancer.

PMID- 12182034
TI  - [Indications for adjuvant therapy of thyroid cancer with radioiodine therapy].
AB  - Indications for complementary radioiodine therapy of differentiated thyroid
      carcinoma are based on its potential to sterilize micrometastases and to ablate
      thyroid remnants. A short summary of the assumptions leading to the combination
      of total thyroidectomy with complementary radioiodine treatment is given in the
      paper. We also present the preliminary results of the evaluation of nearly 800
      patients with differentiated thyroid carcinoma treated surgically in various
      centres and referred to our department for radioiodine therapy. Total 10-year
      survival was significantly higher in patients in whom complementary radioiodine
      therapy had been introduced after total or less than total thyroidectomy. The
      upper limit of postoperative 24 h thyroid uptake of 20% before radioiodine
      therapy was revealed as a good criterium for the optimal long-term effects.
      However, a gradual decrease of postoperative 131I uptake has been observed, thus,
      this upper limit is probably to be lowered in future.

PMID- 12182035
TI  - [Radiobiologic basis for using 131I to treat patients with thyroid cancer].
AB  - The basic biological principle for 131I treatment of patients with thyroid cancer
      is the ability of well-differentiated tumor cells to uptake iodine. The
      absorption of adequate activities of radioiodine may sterilize primary tumor
      cells and the metastatic deposits. The basic factors which determine the
      effectiveness of radioiodine treatment include the effective half-life of 131I,
      the discrete energy of its beta decay, the effective range of emitted beta-rays,
      the activity of individual therapeutic doses, the intrinsic ability of tumor to
      uptake radioiodine, and the absorbed total radiation dose. The biological
      factors, which contribute to the effectiveness of radioiodine treatment, can be
      referred to "five Rs" of radiobiology: radiosensitivity, repair, redistribution,
      reoxygenation, and repopulation. The theoretical radiobiological considerations
      suggest that improvements in therapeutic indexes of radioiodine treatment are
      possible, e.g. by unconventional fractionation of 131I, or by combining the
      radionuclide therapy with external-beam irradiation. The net effect of such
      strategies in the clinic is, however, often unpredictable, and remains
      investigational and controversial. This illustrates the need for improved design
      of new research in clinical and experimental radiobiology of radioiodine
      treatment.

PMID- 12182036
TI  - [Early evaluation of treatment effectiveness using 131I iodine radiotherapy in
      patients with differentiated thyroid cancer].
AB  - This paper presents the preliminary results of a prospective randomized trial on
      early effectiveness of 30 mCi versus 60 mCi for ablation of thyroid remnants in
      patients with WDTC after total thyroidectomy. Since April 1998 to January 2000,
      220 patients with papillary thyroid cancer in stage T1b-3, N0-x, M0 had entered
      the study. 106 patients received 60 mCi and 114 received 30 mCi as the first
      ablation dose. The subject for the analysis was the uptake over the neck, post
      therapeutic whole body scintigraphy and Tg level 6 months after ablation. The
      early effectiveness of ablation was estimated using a 5-degree scale: 0--very
      good effect, 1--good effect, 2--dubious effect-required repetition of WBS and Tg
      assessment in 6-12 months, 3--insufficient ablation--required repetition of
      radioiodine treatment, 4--for evident dissemination or local recurrence. RESULTS:
      Grades 0 were obtained in 29 (53%) after 30 mCi (group I) and in 38 patients
      (86%) after 60 mCi (group II). Grades 1 were obtained in group I in 15 patients
      (28%) and in 4 patients (9%) of group II. Grades 2 were obtained in group I in 9
      patients (17%) and in group II in 1 (2.3%). Grade 3 was obtained only in 1 (2%)
      patient after 30 mCi. Grade 4 was obtained in one patient after 60 mCi (2.3%).
      The difference in uptake over the neck in the two groups was statistically
      significant (p < 0.05), although the differences in early effectiveness between
      the both groups according to the 5-degree scale were on the borderline of
      significance (p = 0.075). There was a correlation between uptake before and after
      ablation in 30 mCi group, which was not seen present in 60 mCi group. CONCLUSION:
      For the ablation of thyroid remnants 60 mCi should be considered as a standard
      dose.

PMID- 12182037
TI  - [Use of recombinant human TSH for stimulation of iodine radioisotope uptake in
      metastases of thyroid cancer during therapy with 131I].
AB  - The diagnostics with the use of recombinant human TSH for the follow-up of
      differentiated thyroid carcinoma (DTC) has been already approved. In more than
      400 diagnostic scans, rhTSH proved to be effective in promoting 131I uptake in
      thyroid remnants and DTC metastases in patients receiving suppressive doses of
      thyroxine. However, information about its application in radioiodine treatment of
      DTC are scarce, especially with respect to patients with metastatic disease. In
      this review we have described our own results obtained during rhTSH aided
      radioiodine treatment of 42 patients with advanced DTC with reference to current
      literature data about diagnostic and therapeutic application of rhTSH.

PMID- 12182038
TI  - [Non-iodine-absorbing metastasis of differentiated thyroid cancer--therapeutic
      probe with 13-cis retinoic acid].
AB  - The absence of iodine uptake in metastases of differentiated thyroid carcinoma
      makes them unresponsive to treatment with radioiodine 131I. In many of such cases
      symptomatic treatment remains the only available therapy. The results of studies
      on partial redifferentiation of metastases of thyroid cancer achieved after cis
      retinoid acid therapy have drawn attention to the possibility of restoration of
      iodine uptake in metastases after pretreatment with cis-retinoic acid
      (Roaccutane). 5 patients with iodine uptake-negative metastases of differentiated
      thyroid carcinoma were given Roaccutane in a dose 1.5 mg/kg/24 h daily for 6
      weeks before the therapy with radioiodine. In none of the patients restoration of
      radioiodine uptake in metastases has occurred as shown in post-therapeutic total
      body scintigraphy.

PMID- 12182039
TI  - [Use of 13-cis retinoic acid for treatment of advanced differentiated thyroid
      cancer].
AB  - Retinoids, a large group of compounds structurally related to vitamin A, are able
      to induce redifferentiation of thyroid cancer cells. The aim of the study is to
      present our early results of retinoids redifferentiation therapy of thyroid
      cancer patients. In 15 patients with advanced thyroid cancer, whose cancer foci
      did not concentrate radioiodine, 13-cis retinoic acid (Roaccutan) was given for 6
      weeks before radioiodine treatment. Radioiodine therapy was performed under
      exogenous TSH stimulation (Thyrogen). Three patients were treated twice. The
      planned retinoid dose was delivered to 11 patients. In the other four patients
      the reduction of retinoids dose was necessary due to severe side effects. In post
      therapeutic scintigraphy radioiodine uptake was visible in two out of seven
      patients (29%) with lung metastases, in 5 out of 9 (56%) with locoregional
      disease and in two with bone metastases. On the whole, in 50% of patients
      reinduction of radioiodine uptake was visible, however, in most patients only a
      very discrete one. Thyroglobulin concentration before and after retinoids therapy
      did not differ significantly. CONCLUSIONS: In a subgroup of patients 13-cis
      retinoic acid can induce radioiodine uptake, however, prospective studies in
      larger groups of patients are necessary to prove its clinical application.

PMID- 12182040
TI  - [Problems with radiation protection for adjuvant radiotherapy of thyroid cancer].
AB  - Ablative treatment of thyroid cancer with 131I is associated with the exposure to
      ionizing radiation of not only the target cells but also other cells and organs
      in the patient's body. Thermoluminescent dosimetry showed that the mean dose
      equivalent in ovaries equaled to several dozen mSv when the mean therapeutic dose
      was 2.8 GBq of 131I. In the treated young women the performed ovulation tests
      revealed no dysfunction of the ovaries. The highest dose equivalent in the clinic
      staff would not exceed 20 mSv per year. Accordingly, the dose equivalents to the
      public would not exceed the threshold limit of 1 mSv per year. In order to
      fulfill the requirements of regulations for disposal of radioactive waste and the
      necessity to store the waste for as long as 80 days it is obligatory to utilize
      setting tanks of very large capacity.

PMID- 12182041
TI  - [Power Doppler as a method that is better than color Doppler for evaluation of
      thyroid nodular lesions].
AB  - AIM: The evaluation of usefulness of color Doppler sonography and power Doppler
      sonography in the diagnostics of thyroid nodules with the low or absent uptake of
      (99m)Tc-pertechnate. Although scintigraphy is highly sensitive method in the
      diagnosis of cold nodules it is non-specific in the diagnostics of malignant
      changes of thyroid. We tried to investigate the possibility to improve the
      diagnostic accuracy of sonography. MATERIAL AND METHODS: 122 cold thyroid nodules
      were investigated with linear 7.5 Mhz Doppler probe. The flow pattern in power
      Doppler and color Doppler were correlated with cytologic and histopathologic
      examination. RESULTS: According to cytology, PD has better sensitivity and
      specificity than CD; consecutively-100% vs. 86.6% and 93.4% vs. 84.1%.
      CONCLUSIONS: 1. Power Doppler can detect low blood flow in small blood vessels,
      observed in thyroid cancer. 2. Power Doppler allows the best nodules selection
      for fine-needle biopsy than color Doppler.

PMID- 12182042
TI  - [Environmental radiation exposure of a thyroid cancer patient resulting from
      adjuvant iodine radiotherapy].
AB  - The aim of the study was to evaluate radiation risk in the environment of
      patients treated with 131I as an ablative therapy following radical surgery for
      the differentiated thyroid cancer. The activities of radioiodine used in this
      form of therapy approximate 2.8 GBq (76 mCi) and the in cases of the cancer
      metastases to other organs may be as high as 7.4 GBq (200 mCi). Dose equivalent
      rates were estimated in nine seated patients at the level of the thyroid close to
      the gland surface, and 0.5 and 1 m away from it. The measurements were performed
      at one, 24, 48, 72, 96, 120, 144, and 168 hours after the injection of 131I. The
      dose equivalent rates at various distances from the thyroid surface at different
      times were approximated with the exponential function by the least square method.
      Then, the dose equivalents were calculated from the moment of 131I application to
      the moment of the total removal of the isotope from the organism. From this
      relation, time intervals after which the annual threshold doses of 1, 5, and 50
      mSv would be exceeded were computed as the function of the applied 131I activity.
      The results of the present study indicate that attendants of the patients treated
      with 131I will not be exposed to the doses of ionising radiation exceeding the
      acceptable annual thresholds provided with the limited time intervals. In
      addition, the present results may be useful in elaborating procedures of dealing
      with and handling the patients during their stay at hospital, at home, and at
      work.

PMID- 12182043
TI  - [Clinical-pathomorphologic preparation of patients after surgical treatment of
      differentiated thyroid cancer to adjuvant treatment with 131I].
AB  - Thyroid cancer treatment includes: surgery, radioiodine therapy, thyroxine
      therapy and radiotherapy. Selection of treatment's strategy depends on
      histopathological evaluation, age of patient and iodine uptake. The aim of the
      analysis was to verify how the medical documentation of patients treated by
      surgical treatment was prepared. All patients were directed to the Department of
      Endocrinology, Holycross Cancer Center in Kielce. Analysis encompassed 33
      patients classified to 131I therapy for the first time. In each case patient's
      medical documentation and histopathological diagnosis made in Department of Tumor
      Pathology, Holycross Cancer Center, were compared. RESULTS: A conformity with
      primary cancer diagnosis was obtained in all but one patient in whom pathological
      consultation did not confirm oxyphilic carcinoma. In four cases the type of
      cancer was changed as a result of repeated consultation. pTMN classification was
      stated in 23 primary pathologic examination cases. After consultation of slides
      and inspection of surgery protocol, total or partial pTNM stage was obtained in
      other 9 patients. CONCLUSIONS: Establishment of diagnostic and therapeutic
      algorithm, accepted on Conference in Szczyrk, 1995 is inadequately executed in
      small centers. Routine consultation of histopathological slides creates a
      possibility to make a proper choice of treatment's strategy.

PMID- 12182044
TI  - [The role of teleradiotherapy in treatment of thyroid cancer].
AB  - The role of teleradiotherapy in the treatment of patients with thyroid cancer is
      presented. The indications for external irradiation include patients with:
      primary inoperable disease or inoperable recurrence, microscopic or gross
      residual disease after surgery, high risk of local regional failure, and
      metastatic thyroid cancer, especially with skeletal, brain and mediastinal
      metastases.

PMID- 12182045
TI  - [Prospective analysis of criteria for interpreting measurements of thyroglobulin
      serum concentration during conditions of endogenous TSH stimulation in serum of
      patients with differentiated thyroid carcinoma].
AB  - The aim of this study was the assessment of diagnostic value of thyroglobulin
      serum measurement in patients with DTC during endogenous TSH stimulation.
      Thyroglobulin was measured by immunofluorometric method (Delfia-Wallac) in
      patients after combined surgery and I131 ablation. Predictive values for two
      threshold levels 10 and 30 ng/ml were compared. At 5 years follow up it has been
      demonstrated, that Tg values higher than 10 ng/ml were the true signals of DTC
      relapse only in 46% patients. Tg values higher than 30 ng/ml were associated with
      disease progression in 65% of patients. Thus, we accept Tg concentration of 30
      ng/ml measured during endogenous TSH stimulation as a good cut-off limit for the
      detection of DTC progression. Reduction of this threshold up to 10 ng/ml is
      associated with the increased risk of false positive results.

PMID- 12182046
TI  - [Comparison of efficacy of various methods of thyroglobulin measurements in
      differentiated thyroid cancer].
AB  - Monitoring patients with differentiated thyroid carcinoma (DTC) by thyroglobulin
      (Tg) measurements requires selecting optimal methods used for detection of this
      marker. An increase the thyroglobulin concentration in serum is a predictor of
      tumor recurrence. All serum thyroglobulin assays can be falsified by presence of
      Tg autoantibodies, which are present in approximately 20% of DTC patients. The
      aim of this study was a comparison of the clinical utility of two different
      methods for determining serum Tg concentration in monitoring patients with DTC
      during thyroxine treatment. Tg concentration was measured in serum samples of
      1530 patients with DTC during replacement thyroid hormone using two methods:
      fluoroimmunometric assay (IFMA) Wallac Delfia Thyroglobulin and immunoradiometric
      assay (IRMA) Brahms DYNOtest Tg-S. 1847 values of Tg concentration and recovery
      test detected between 1992 and 1995 years using IFMA methods and 1187 values of
      Tg and thyroglobulin autoantibodies concentration measured in 2000 year using
      IRMA methods were also included. The correlation between Tg values in all
      patients group wasn't good (r = 0.83; p < 0.05), but when we excluded patients
      with incorrect recovery test determined by IRMA, the correlation factor was
      higher (r = 0.94; p < 0.05). The estimation of Tg recovery test obtained in IRMA
      assay eliminated from monitoring only 3% patients with DTC, when IFMA assay
      excluded nearly 1/5 patients, whereas the estimation Tg autoantibodies 7% from
      all patients. The IRMA method is the most resistant to interference and allows to
      monitor a reliably greater group of patients with DTC during thyroxine treatment.

PMID- 12182047
TI  - [Thyroglobulin RT-PCR method for detection of lymph node metastases during the
      course of differentiated thyroid cancers].
AB  - In patients with a suspicion of recurrence of differentiated thyroid cancer with
      metastases to lymph nodes, detection of thyroglobulin (Tg) mRNA in fine needle
      biopsy material may support the interpretation of classic cytological examination
      in cases where it fails to detect lymph node involvement early enough. AIM:
      Prospective study of thyroglobulin mRNA detection in neck lymph nodes in patients
      with suspected differentiated thyroid cancer (DTC) metastases. MATERIAL: 70 nodes
      from 60 patients with suspected DTC recurrence were investigated. Patients with
      suspicion of lymph node metastases of other types of cancer were included as a
      control group. Thyroglobulin RT-PCR was conducted in residual material left after
      preparation of cytological smears from fine needle biopsy specimens. Primers
      spanning exons 3-5 were used with 39 cycles of PCR. RNA isolation control and
      cDNA amplification were carried out using GADPH starters. RESULTS: Classical
      cytology confirmed nodal involvement in 22 of DTC patients, RT-PCR Tg was
      positive in 20 of them (91%). Among 48 patients with a suspicion of DTC
      recurrence and negative cytology, Tg mRNA was found twice. One positive RT-PCR
      result was confirmed by repeated cytology conducted 4-6 months later and followed
      by surgery. No positive result of RT-PCR was obtained with other head and neck
      malignancies. The overall specificity was estimated with 98%. CONCLUSIONS: RT-PCR
      Tg shows sufficient specificity to be applied in further studies estimating its
      usefulness in fine needle biopsy for early detection of lymph node metastases in
      differentiated thyroid cancer.

PMID- 12182048
TI  - [99mTc Tetrofosmin in diagnosis of distant metastases from differentiated thyroid
      cancer].
AB  - Technetium 99mTc(TF), non-specific tumor-searching tracer was evaluated for its
      ability to detect distant metastases of differentiated thyroid carcinoma (DTC)
      and its reliability in the follow-up of DTC. Whole body scintigraphy (wbs) was
      performed 20-30 min after intravenous injection of 740 MBq 99mTc tetrofosmin by
      means of a dual-head gamma-camera (followed by spot images if needed) in 61
      patients (pts) with DTC; 52 pts with distant metastases in 131I whole body
      scintigraphy (34) or in other methods (x-ray, CT, ultrasound) (7) or with
      negative 131I whole body scan and elevated thyroglobulin (11). In the group of 52
      pts with signs of neoplasm dissemination, 36 showed positive TF whole body scan
      (69%), 16 (31%) pts were TF-negative. 23 of 34 131I positive wbs were also TF
      positive (68%), 11 out of 34 were TF negative (32%). In a group of 7 pts with
      metastases in x-ray, CT or ultrasound 4/7 were positive (57%), 3/7 were TF
      negative (18%). In a control group of 11 persons (2 diseases-free, 9 with DTC in
      clinical remission) TF whole body scans were negative in all cases. CONCLUSIONS:
      Technetium 99mTc tetrofosmin is clinically useful for detecting distant
      metastases of differentiated thyroid carcinoma and deserves complementary
      clinical application in follow-up in such patients.

PMID- 12182049
TI  - [Accuracy of ultrasound-guided fine-needle aspiration biopsy in diagnosis of
      changes in thyroid nodular lesions].
AB  - The aim of this study was to compare the results of US-FNAB with definitive
      histological examination of thyroid nodular lesions. 590 patients who underwent
      surgery were reviewed (473 females, 117 males, ranging in age from 9 to 81 years,
      average 36 years). Histological evaluation of cytologically diagnosed benign
      nodules revealed nodular goiter in 407 cases (91.5%), Hashimoto's thyroiditis in
      2 (0.4%), follicular adenoma in 31 (7%), papillary carcinoma in 2 (0.4%) and
      follicular carcinoma in 3 (0.7%). In the cytological group of follicular nodule
      (n = 71) histological diagnoses included: nodular goiter in 11 cases (15.5%),
      follicular adenoma in 36 (50.7%), papillary carcinoma in 2 (2.8%), follicular
      carcinoma in 20 (28.2%). The diagnosis of papillary carcinoma (n = 65) was
      confirmed histologically in 59 cases (90.8%), in the remaining 6 cases
      Hashimoto's thyroiditis and medullary carcinoma were diagnosed. In the cases
      diagnosed cytologically as medullary carcinoma (n = 8) histological diagnoses
      included: medullary carcinoma in 7 cases (87.5%). The cytological diagnosis of
      anaplastic carcinoma (n = 1) was confirmed histologically. These results support
      the value of US-FNAB in the diagnostics of thyroid neoplasms. US-FNAB performance
      was as follows: sensitivity 78%, specificity 97%, accuracy 92%, 2.3% of false
      positive and 6.1% of false negative results.

PMID- 12182051
TI  - [Treatment with L-thyroxine for differentiated thyroid carcinoma].
AB  - Differentiated thyroid carcinoma (DTC) is one of malignant neoplasms with a very
      good prognosis and low mortality rate provided a proper therapy and its
      systematic monitoring is given. DTC treatment consists of surgery, radioiodine
      and L-thyroxine therapy. L-thyroxine therapy in DTC should be both substitutive
      and suppressive. Substitutive therapy consists in the removal of the lack of
      thyroid hormones symptoms so that the serum TSH is about 1 mU/l. Suppressive
      therapy consists in complete inhibition of TSH secretion by pituitary gland. This
      prevents from the regrowth and inhibition of carcinoma progress in patients with
      evident or residual neoplasmic disease. Although complete suppressive therapy
      (TSH less than 0.05 mU/l) is the most recommended one, in patients with low
      recurrence risk incomplete suppression can be used (TSH = 0.1-0.3 mU/l).
      Suppressive L-thyroxine doses may give side-effects such as: cardiac signs
      (arrhythmia, coronary or heart insufficiency), decrease in bone mineral density
      with osteopoenia or osteoporosis or subclinical hyperthyroidism. However, the
      side-effects of the suppressive L-thyroxine doses may be symptomatically treated
      (with beta-blockers, biphosphoniates).

PMID- 12182052
TI  - [Evaluation of effects of L-thyroxine therapy in differentiated thyroid carcinoma
      on the cardiovascular system --prospective study].
AB  - Patients with differentiated thyroid carcinoma are treated by thyreoidectomy,
      followed by radioiodine treatment. A life-time suppressive therapy with L
      thyroxine is also indicated. However, it may cause cardiovascular side effects.
      The aim of the study was a prospective evaluation of the left ventricle
      hypertrophy in patients treated with suppressive doses of thyroxine. A
      significant rise in left ventricular mass and mass index was noted during the
      first year of therapy and could be prevented by a simultaneous treatment with low
      doses of bisoprolol.

PMID- 12182050
TI  - [Evaluation of the relationship between chosen factors and results of whole body
      scintigraphy with 131I in patients with differentiated thyroid cancers].
AB  - Treatment and diagnostics with 131I play an important role in patients with
      differentiated thyroid cancer (DTC) after thyreoidectomy. The aim of the study
      was to assess the influence of some factors on ablative therapy results. Fifty
      seven patients with DTC were investigated (44 females--mean age 46.6 yrs, 13
      males--mean age 55.6 yrs.). Papillary thyroid cancer was diagnosed in forty five
      patients (79%) however, follicular thyroid cancer in the others (21%). We
      performed post-therapeutic whole-body scan (WBS) after high fixed doses of 131I
      (median = 75 mCi) and six months later diagnostic WBS (mean 4.3 mCi) in every
      patient. Postoperative radioiodine uptake, levels of TSH and thyroglobulin (Tg)
      serum concentrations were assessed after thyroid hormones withdrawal before
      imaging. The absence of radioiodine uptake in the thyroid bed (effective
      ablation) was observed in 64.9% of patients. In other cases scans showed
      significantly diminished uptake of the tracer in the remnants. Statistically
      significant difference in TSH levels before and after radioiodine therapy (75.6
      vs. 106.7 microIU/ml, p < 0.001) was found in all patients. However,
      effectiveness of the ablative therapy did not depend on radioiodine uptake, TSH
      and Tg levels before radioiodine treatment.

PMID- 12182053
TI  - [Evaluation of bone density in women after thyroid cancer surgery and treatment
      with suppressive doses of L-thyroxine].
AB  - The aim of this work was to evaluate the degree of bone resorption and incidence
      of osteoporosis in female postmenopausal patients with differentiated thyroid
      cancer treated with suppressive doses of thyroxine. During the regular follow-up
      of women with differentiated thyroid cancer, densitometry of lumbar spine (L2-L4)
      and femoral head were performed. urine concentration of deoxypyridinoline and
      calcium-phosphate metabolism were also evaluated. Osteoporosis was diagnosed in
      11% of patients, all without hormone replacement therapy (HRT). Mean bone density
      was significantly higher in patients treated with HRT. A decrease in bone mass
      was related to the duration of thyroxine therapy. The best results of bone mass
      density were obtained in patients on HRT and with short duration of thyroxine
      therapy. Deoxypiridinoline estimation did not exhibit significant differences
      between groups, however it was useful in the individual evaluation of bone
      resorption.

PMID- 12182054
TI  - [Hormonal replacement therapy in women after surgery for thyroid cancer treated
      with suppressive doses of L-thyroxine].
AB  - Total thyroidectomy followed by 131I ablation and thyroxine suppressive therapy
      is recommended for the treatment of differentiated thyroid carcinomas. Thyroxine
      should be given at a dose sufficient to suppress TSH to low or undetectable
      levels. These patients are categorized as subclinical hyperthyroidism subjects.
      Some cardiovascular effects of subclinical hyperthyroidism, such as an increase
      in left ventricular mass and accelerated bone loss, should be taken into
      consideration. Estrogens reduce the loss of bone mass in thyrotoxic
      postmenopausal patients and have cardioprotective effects. The relatively high
      incidence of thyroid carcinoma in women suggests that estrogen and/or
      progesterone may be important for the development of these neoplasms.
      Immunohistochemical study has established that steroid receptors are present in
      thyroid tissue. Many authors suggest that estrogens by itself do not appear to
      affect the natural history of thyroid cancer. Besides the thyroid, active iodide
      transports catalysed by the sodium/iodide symporter occurs in the lactating
      mammary gland. An increased risk of breast carcinoma in women with thyroid
      carcinoma due to carcinogenicity of radioiodine has been reported by some but not
      all investigators. Hormone replacement therapy in the thyroxine treated
      postmenopausal women consists in conventional oral or transdermal estrogen
      combined with progesterone. In some cases the daily dose of thyroxine should be
      increased to achieve TSH suppression.

PMID- 12182055
TI  - [Pregnancy in women with thyroid cancer treated with suppressive doses of L
      thyroxine].
AB  - The aim of the study was to estimate the dose of thyroxine required by pregnant
      women who had undergone total thyreoidectomy and radioiodine treatment for
      thyroid cancer. Material consisted of 4 pregnant women, aged mean 30.8 years. One
      of patients was studied during 2 consecutive pregnancies. The daily mean dose of
      thyroxine was 175 micrograms. The control group consisted of 7 women with primary
      hypothyroidism aged mean 33.5 years, who were treated with replacement doses of
      thyroxine. One of them was pregnant twice. The mean daily dose of thyroxine was
      106.3 micrograms. The estimation of TSH, fT4 were repeated every 4 weeks.
      RESULTS: In all cases natural deliveries took place. All infants were alive and
      had no congenital malformations and no clinical or biochemical thyroid
      dysfunction was found. Pregnant women treated for thyroid cancer needed to have
      optimized their suppressive therapy by increasing the dose of thyroxine by 26% at
      the first trimester, 27% at the second and 38% at the last one. Statistically
      significant increase was found at the 1st trimester of pregnancy and it remained
      at the same level till the delivery. Pregnant hypothyroid women needed to have
      optimized their replacement thyroxine therapy by increasing of the dose by 53% at
      the first trimester, by 49% at the second and by 53% at the last one. Similarly
      to the 1st group of patients, we noticed statistically significant increase at
      the 1st trimester of pregnancy. CONCLUSION: In pregnant women who have been
      previously treated for thyroid cancer the suppressive dose of thyroxine needs to
      be increased by 26-38% which is slightly less than the increase of the
      replacement dose in hypothyroid pregnant women.

PMID- 12182056
TI  - [Parathyroid hypofunction after total thyroidectomy for differentiated thyroid
      carcinoma--perspectives after long term observation and treatment].
AB  - Hypoparathyroidism remains a serious complication of total thyroidectomy for
      differentiated thyroid carcinoma (DTC). In Brachytherapy Department 952 patients
      affected with DTC were followed up in the years 1996-2000. Radical total
      thyroidectomy was performed in 235 (24.6%) of cases, while the other 717 patients
      underwent complete rethyroidectomy. The incidence of hypoparathyroidism following
      radical operation and after complete rethyroidectomy was 15.74% and 23.43%,
      respectively. In patients operated in our institution, blood for calcium was
      analyzed daily for five days following the surgery. If calcium level was normal
      the next measurement was performed 4-5 weeks thereafter. Hypoparathyroidism was
      diagnosed later in postoperative period in many patients operated elsewhere.
      Asymptomatic hypocalcemia during the first week after the operation requires oral
      administration of calcium. If hypocalcemia requiring intravenous calcium
      supplementation does not resolve in a few days, vitamin 1(OH)D3 is introduced.
      Vitamin 1(OH)D3 and calcium carbonate play the main role in management of
      persistent hypocalcemia. In case of marked hypercalciuria thiazid diuretics are
      instituted. Low-phosphate diet is recommended. The aim of treatment of
      hypoparathyroidism is to restore normal serum calcium level with calciuria not
      exceeding 5 mg/kg/24 h, so to avoid hypocalcemic complications as well as vitamin
      D intoxication.

PMID- 12182057
TI  - [Consequences of clinical genetic analysis of RET proto-oncogene].
AB  - Preliminary results of treatment of inherited medullary thyroid carcinoma,
      diagnosed primarily with genetic analysis of mutation of protooncogene RET are
      presented. Among 16 carriers of mutation identical with mutation diagnosed
      earlier in proband, there were 4 patients with clinically obvious medullary
      thyroid carcinoma and 12 asymptomatic carriers. In all patients, in whom
      calcitonin level was increased preoperatively, its normalization was obtained.
      The paper summarizes these aspects of cooperation between geneticians and
      physicians in which diagnostic results influence clinical decisions (indication
      and time of thyroid and lymph nodes surgery and it's spectrum, range of
      diagnostic procedures towards pheochromocytoma and parathyroid hyperplasia in
      relation to the found mutation).

PMID- 12182059
TI  - [Differential criteria between papillary and follicular thyroid carcinoma-
      initial conclusions from a multicenter trial].
AB  - Histopathological diagnosis of thyroid cancer is difficult and requires much
      experience. Pathologists have to know many histopathological variants and be
      aware of the current diagnostic criteria. The aim of the study was to unify
      criteria applied all over the country and compare whether the accuracy of
      diagnosis has changed in the course of the last fifteen years. In a multicenter
      trial, 36 pathologists from 25 centers reevaluated 232 thyroid tumors operated
      between 1985-1998. The reference diagnosis was given on the basis of evaluation
      made by four experienced pathologists. The two-step analysis was performed. At
      first, the accuracy of the diagnosis of malignant neoplasm was evaluated. Then,
      the accuracy of the diagnosis of the cancer histotype was analyzed, with
      estimation of kappa coefficients and their asymptomatic standard error.
      Comparison of primary and reference diagnoses revealed statistically significant
      differences--in 17% of cases the primary diagnosis of cancer was not confirmed by
      experienced pathologists. Kappa coefficient for the diagnosis of cancer histotype
      was 0.53 + 0.06. On the contrary, the diagnoses made by the participants of the
      trial did not differ significantly from the reference ones. Kappa coefficient for
      the diagnosis of cancer histotype was significantly higher than for primary
      diagnoses with 0.63 +/- 0.10 (p < 0.001). The first results of the multicenter
      trial indicated that the most frequent diagnostic error made at primary diagnosis
      was the overdiagnosis of follicular thyroid carcinoma. Thus, a summary of strict
      criteria for papillary and follicular thyroid carcinoma is also given.

PMID- 12182058
TI  - [Proto-oncogene RET somatic mutations in medullary thyroid carcinoma].
AB  - Somatic mutations of the RET protooncogene are present in 23-68% cases of
      sporadic medullary thyroid carcinoma (MTC). The aim of the study was to introduce
      the RET somatic mutations analysis in tumor tissue as well as to evaluate their
      types and frequencies in postoperative specimens of MTC patients treated in the
      Center of Oncology in Gliwice. MATERIAL: 14 tumor tissues obtained from sporadic
      MTC patients and two control groups--six and four specimens from patients with
      MEN 2A and MEN 2B syndrome respectively. METHODS: Tumor tissue DNA isolation
      followed by PCR amplification of RET exons 10, 11, 13, 14, 16 and automated,
      fluorescent sequencing of PCR products. We identified somatic mutation ATG > ACG
      in codon 918, exon 16 in 7 of 14 (50%) of analyzed sporadic MTC cases. We also
      found one deletion/insertion mutation in RET exon 11 that encompasses cysteine
      codon 634 and has not been published so far. The types and frequencies of found
      RET gene mutations were similar to previously reported. The analysis of RET
      somatic mutations supports the differentiation between the sporadic and inherited
      MTC. The presence of somatic mutation and its simultaneous absence in the
      germline proves sporadic type of cancer.

PMID- 12182060
TI  - [Results of treating medullary thyroid carcinoma: the differences between
      sporadic and inherited forms].
AB  - Medullary thyroid carcinoma (MTC) can be divided into two subgroups: sporadic or
      inherited. Hereditary form of MTC is often believed to be form with better
      prognosis than sporadic one. In this study the differences in MTC prognosis in
      Polish population of patients was analyzed. The group of 169 patients with MTC
      was examined. Hereditary cancer was stated in 48 (28%) patients. The median age
      of disease onset was 41 years (from 7 to 71 years). Genetic examination of RET
      protooncogene was performed in all patients. The calcitonin and CEA serum level
      analysis and radiological and radioisotopic examinations were used for monitoring
      of the disease course. Nineteen cases of MEN 2A syndrome, 11 cases of MEN 2B one
      and 18 cases of non classified familial MTC were recognized among patients with
      inherited MTC. Significantly lower age of disease onset in inherited MTC than in
      sporadic one was observed (27 years vs. 43.7 years, p < 0.001). Local or nodal
      recurrence was observed in 22 (13%) patients, distant metastases were stated in
      21 (12%) patients. Basal or stimulated serum calcitonin level was increased in 85
      (50%) patients. No significant differences between sporadic and inherited disease
      were observed. Eight patients died during observation, including 3 patients with
      sporadic MTC and 5 patients with inherited MTC. The updated 10-year survival rate
      was 97% in patients with sporadic MTC; in hereditary MTC it was about 20% worse.
      The complications related to the presence of adrenal tumors were the main reason
      for death in MEN2 and no significant differences in the course of MTC itself were
      observed.

PMID- 12182061
TI  - [Medullary thyroid carcinoma--personal observations].
AB  - The paper presents the rules of surgical treatment in medullary carcinoma of the
      thyroid gland based on own experience and survey of literature. Changing trends
      in diagnostic and therapeutic approach were described. The results achieved
      encouraged authors to find some conclusions. Long term results of therapy depend
      mostly on stage of disease in time of initial surgery, radicality of primary
      operation and further supportive treatment. Systematic follow-up after surgery
      makes it possible to early detect the recurrence and has an influence on survival
      rate. In cases of poorly differentiated medullary thyroid cancer even radical
      surgical procedure followed by the appropriate supportive treatment results in a
      not satisfactory survival.

PMID- 12182062
TI  - [Diagnosis and treatment of malignant thyroid neoplasms. Recommendations of the
      Scientific Committee of the 2nd Scientific Conference "Thyroid Carcinoma 2000"].

PMID- 12182063
TI  - [Criteria for histopathologic diagnosis of thyroid cancer in a quick test of
      accuracy].
AB  - A quick test of accuracy of histopathological diagnosis of thyroid carcinoma was
      performed in May 2000 during the meeting of Polish thyroid cancer group
      (Committee for Epidemiology, Diagnosis and Treatment of Thyroid Carcinoma). 29
      pathologists participated in the test and evaluated 8 cases of thyroid carcinoma
      and 14 benign thyroid lesions. All cases were chosen from the current material
      sent for pathologic evaluation to the Institute of Oncology in Gliwice due to
      diagnostic difficulties. In total, 591 diagnoses were made and were the subject
      of the presented analysis. They were compared with reference diagnosis in two
      aspects. First, the accuracy of the distinction between malignant and benign
      lesions was evaluated. 72.5% of diagnoses were concordant with the reference. The
      false diagnosis of cancer in a benign lesion was observed 133 times (22.5% of all
      diagnoses). A reverse error--a false exclusion of cancer--was seen in 29
      diagnoses (4.9%). Chi 2 test revealed a statistically significant difference
      between the participants' diagnoses and reference ones (p < 0.0001).
      Overdiagnosis of cancer was the most frequent at the diagnosis of follicular or
      oxyphilic cancer. With reference to the diagnosis of cancer histotype, concordant
      diagnoses were seen in 40-47% of cases with the lowest accuracy of the diagnosis
      of oxyphilic (40% of correct diagnoses) and follicular (50%) cancer. The causes
      of false diagnoses may be divided in two groups: sample-related causes (sampling
      of surgical specimens, lack of standard description, insufficient number of
      samples, poor quality of staining) and diagnostic errors: non-compliance with
      diagnostic criteria and inappropriate setting of diagnoses, which require
      immunohistochemical confirmation.

PMID- 12182064
TI  - [Rearrangement of the RET gene in papillary thyroid carcinoma].
AB  - The RET/PTC oncogenes, activated forms of the RET protooncogene, almost
      exclusively found in papillary thyroid carcinoma (PTC). What is more, the
      targeted expression of RET/PTC in mice leads to the development of thyroid tumors
      very similar to human PTCs. In all RET/PTC types the RET tyrosine kinase domain
      is fused to the N-terminus of ubiquitously expressed genes that is capable of
      ligand-independent dimerization. The majority of RET/PTC identified consists of
      two types which results from the inversion of chromosome 10: RET/PTC1 and
      RET/PTC3. The prevalence of RET/PTC in papillary thyroid carcinomas of thyroid
      varies widely from a few to about 80% with the highest frequency in tumors
      arising in children after ionizing radiation. In Polish population the frequency
      of RET rearrangements in papillary cancers is 27%, although, it was reported to
      be twice higher in young patients (50% in patients younger than 21 at operation).
      Correlation with clinical outcome as well as prognostic value of RET/PTC is
      controversial. Some authors suggest that it predicts metastases, others found
      rearranged RET in more favourable, slow growing tumors. RET/PTC3 seems to be
      associated with solid/follicular variant PTC and short latency period (it is
      found more frequently in children) whereas RET/PTC1--with classic PTC variant and
      long latency.

PMID- 12182065
TI  - [Prognostic significance of selected oncogene and suppressor gene expression in
      follicular thyroid carcinoma].
AB  - Oncogene and suppressor gene expression (cyclin D, p21WAF1, nm23-H1, Rb1,
      p16INK4A, and p53) was evaluated in 23 follicular thyroid carcinomas diagnosed in
      20 women and 3 men operated or reoperated in Institute of Oncology in Gliwice in
      years 1992-1999. Positive reaction with p16INK4A, Rb1 and cyclin D1 antibodies
      was observed in all tumors, with nm23-H1 in 22 cases. The presence of p21WAF1 was
      stated in 8 cases (34.8%) and p53 in 7 cases (30.4%). A simultaneous presence of
      expression of p53 and lack of expression of p21WAF1 was stated three times and in
      two cases were accompanied by distant metastases. This pattern of expression was
      only rarely observed in minimally invasive follicular cancer. The prognostic
      significance of simultaneous immunohistochemical analysis of p53 and p21WAF1 in
      follicular thyroid carcinoma is suggested and has to be proved in further
      studies.

PMID- 12182066
TI  - [Poorly differentiated carcinoma of the thyroid--immunohistochemical evaluation
      of p53 and p27 protein expression].
AB  - Thyroid carcinomas represent a broad spectrum of tumours with different biologic
      behaviours. The gap between the indolent course of well-differentiated papillary
      and follicular carcinomas and the very aggressive behaviour of anaplastic
      carcinomas is filled by variants of thyroid carcinoma with intermediate
      prognosis, designated in the literature as poorly differentiated (with insular,
      trabecular and solid patterns) and tall/columnar cell variant of papillary
      carcinoma. The study has been carried out in 103 patients who had thyroid cancer
      with various grade of differentiation. The diagnostic significance of p53 and p27
      expression in tumor cells has been investigated by immunohistochemical analysis.
      Well differentiated carcinomas have exhibited the lowest p53 staining frequency,
      the expression has been higher in poorly differentiated carcinomas and 100% of
      anaplastic carcinomas have been positive p27 immunohistochemistry has been
      positive in 80% of investigated carcinomas (in 15% strong positive reaction). In
      the group of poorly differentiated tumours positive reaction has been observed in
      75% cases (in 15% strong positive reaction). Our data suggest that expression of
      p53 and p27 seems to have limited routine diagnostic significance, but p53
      positivity is a good marker of tumour progression.

PMID- 12182067
TI  - [Expression of protein p53: the marker of low neoplastic cell differentiation in
      thyroid carcinoma].
AB  - The aim of the study was to evaluate the frequency of positive staining of p53
      protein in the course of thyroid carcinoma and to establish the prognostic value
      of such expression. MATERIAL AND METHOD: Immunohistochemical staining of frozen
      sections was performed in 159 patients with thyroid carcinoma (139 females and 29
      males). The average age was 50.4 years. All patients have been followed-up for at
      least 5 years and the average time of observation was 10.7 years. There were 46%
      patients with papillary carcinoma, 39% with follicular carcinoma and 15% with
      poorly differentiated thyroid carcinoma in the study group. Additionally,
      staining was performed in 6 cases of anaplastic carcinoma. The expression of p53
      protein was assessed by two-degree scale: a medium (10% of cells with positive
      staining) and strong (50% of positive staining). RESULTS: In the group of 135
      patients with well differentiated thyroid carcinoma the expression of p53 protein
      has been found in 55 cases (40.1%) but significantly more often in medium (69.1%)
      than in strong degree (30.9%). Significantly more often in expression has
      occurred among patients with poorly differentiated carcinoma (66%) and anaplastic
      carcinoma (100% of patients with strong expression in all cases). Comparing the
      frequency of p53 protein expression on every stage of disease, no significant
      difference has been found. The presence of p53 protein has not correlated with
      reduced changes in survival. In multivariate analyses the expression of p53
      protein have not shown prognostic value. CONCLUSION: The expression of p53
      protein has concerned the poorly differentiated carcinomas of thyroid and has not
      correlated with the stage of disease. No influence of expression on clinical
      course of the well differentiated thyroid carcinoma has been found. Worse
      prognoses have correlated with poor differentiated thyroid cancer cases and with
      strong expression of p53 protein.

PMID- 12182068
TI  - [Sodium-iodide cotransporter in gene therapy].
AB  - Since cloning (1996) and characterization of the sodium iodide symporter (NaIS)
      gene, several investigators have studied the possibility of novel cytoreductive
      gene therapy based on NaIS gene. The NaIS present in membranes of the thyroid
      cells is responsible for the capacity of the thyroid to concentrate iodide. The
      strategies of these methods explore NaIS gene transfer into non-thyroidal cancer
      cells. NaIS gene transfer has been shown to be capable of inducing radioiodine
      accumulation in vitro in several non-thyroidal cell lines. Successful
      transfection with NaIS gene was demonstrated in human ovarian adenocarcinoma,
      prostatic adenocarcinoma, human glioma, melanoma, colon carcinoma, lung or
      mammary gland cell lines. NaIS transfected tumor cells accumulated radioiodine
      highly enough to elicit therapeutic response to 131I in vitro and in vivo. These
      data have suggested potential role of NaIS as a novel cancer therapy approach for
      a targeting radiotherapy for non-thyroidal cancers.

PMID- 12182069
TI  - A method for constructing reshaping single-domain antibody.
AB  - The aim of this research was to demonstrate a novel and practical method for
      constructing reshaping Single-domain antibodies. Different from other methods,
      our method does not need to model the configuration of antibodies with specific
      sequences to determine the sequences of human acceptor FRs and then determine
      which amino acid residues in human acceptor FRs should be substituted. Most
      importantly, reshaping and enhancing the antigen binding affinity shared one
      procedure at the same time. Using this method, the reshaping anti-CD28 single
      domain antibodies were constructed. According to the amino acid sequence of a
      mouse anti-human CD28 monoclonal antibody VH, two most homologous sequences of
      human antibodies were selected from GenBank and one of them was used as a main
      framework region for constructing the reshaping antibody. Before the original
      mouse antibody CDRs were inserted into the human acceptor FRs, some amino acid
      residues which were different from those of the original mouse antibody in the
      corresponding positions of the human acceptor FRs were determined or
      alternatively mutated by their conservative properties in Kabat classification.
      When the synthesized nucleotide fragments in different length were spliced by
      overlap PCR into the entire reshaping genes, Taq DNA polymerase and high Mg2+
      concentration were used to introduce more mutation in FRs and CDRs randomly. A
      phage library was constructed using these PCR products and several reshaping
      Single-domain antibodies with high antigen binding affinity were selected after
      three rounds of panning. Two of them were expressed in E. coli BL21 (DE3). The
      antigen-binding affinity of refolded proteins was still in a high level measured
      by ELISA. These results suggested that this method was feasible and efficient for
      constructing reshaping Single-domain antibodies.

PMID- 12182070
TI  - [Origins and migrations of Bouyei people in China--insights from Y chromosome and
      mitochondrion].
AB  - The frequency of Y-chromosome haplotypes consisted of thirteen single nucleotide
      polymorphism alleles in Bouyei people was investigated using PCR-RFLP. And the
      polymorphism of mitochondrial DNA Region V was studied. Nine Y-chromosome
      haplotypes (H1, H4, H5, H6, H7, H8, H9, H11, H12) and two mtDNA alleles (9-bp
      deletion) were obtained in the samples. The frequency distribution of these
      haplotypes and mtDNA polymorphisms in Bouyei people were very similar to that in
      Daic speaking populations including Zhuang, Li, Dong, and Yao people from Jinxiu,
      indicating a close genetic relationship among those populations implicating a
      common ancestry. A hypothesis of the origin of Bouyei people was proposed.

PMID- 12182071
TI  - [Polymorphic loci and polymorphism analysis of short tandem repeats within XNP
      gene].
AB  - To select polymorphic short tandem repeat markers within X-linked nuclear protein
      (XNP) gene, genomic clones which contain XNP gene were recognized by homologous
      analysis with XNP cDNA. By comparing the cDNA with genomic DNA, non-exonic
      sequences were identified, and short tandem repeats were selected from non-exonic
      sequences by using BCM search Launcher. Polymorphisms of the short tandem repeats
      in Chinese population were evaluated by PCR amplification and PAGE. Five short
      tandem repeats were identified from XNP gene, two of which were polymorphic. Four
      and 11 alleles were observed in Chinese population for XNPSTR1 and XNPSTR4,
      respectively. Heterozygosities were 47% for XNPSTR1 and 70% for XNPSTR4. XNPSTR1
      and XNPSTR4 localized within 3' end and intron 10, respectively. Two polymorphic
      short tandem repeats have been identified within XNP gene and will be useful for
      linkage analysis and gene diagnosis of XNP gene.

PMID- 12182072
TI  - [High expression of human FIX(hFIX) in transgenic mice directed by goat beta
      casein gene promoter].
AB  - To probe the feasibility of efficient production of human clotting factor
      IX(hFIX) with the approach of mammary gland bioreactor of transgenic animals, we
      constructed hFIX mammary gland expression vector containing promoter, exon 1,
      intron 1 and exon 2 of the goat beta-casein gene about 6.7 kb fragment as well as
      full-length of hFIX cDNA and its modified intron 1 sequence. By using transgenic
      products and 12 transgenic founders (9 female, 3 male) were produced, and the
      integration rate thus was 11.2%. ELISA assay and Western blot showed that the
      milk of 8 female transgenic mice had hFIX expression with high clotting
      activities. The highest hFIX expression in the milk of one transgenic mouse
      reached 52.9 mg/L, and the highest clotting activity of the transgene milk was
      279.2%. FISH experiments indicated that hFIX DNA was integrated in different
      chromosomes in different mice. This result indicated that the hFIX mammary gland
      expression vector based on the goat beta-casein promoter can efficiently direct
      high expression of hFIX gene in the milk of transgenic mice, which maintained
      high clotting activity.

PMID- 12182073
TI  - Preparation of Meloidogyne javanica near-isogenic lines virulent and avirulent
      against the tomato resistance gene Mi and preliminary analyses of the genetic
      variation between the two lines.
AB  - Meloidogyne javanica, reproducing by mitotic parthenogenesis, is an economically
      important pathogen of a wide range of crops. A pair of near-isogenic lines
      virulent and avirulent toward the tomato resistance gene Mi were prepared for M.
      javanica by continuously selecting an avirulent population on the resistant
      tomato cultivar Momotaro over 19 generations. Random amplified polymorphic DNA
      (RAPD) analysis with 102 primers revealed that RAPD patterns were highly
      conserved between the virulent and avirulent lines, confirming that the two lines
      were genomically very similar. Nevertheless, with one of the primers a distinct
      polymorphic fragment, specific for the avirulent lines, was amplified. Southern
      hybridization results indicated that the polymorphic fragment and its homologs
      were deleted from the genome of the virulent line during the process of virulence
      acquisition. Sequence analysis and homology searches of public data bases,
      however, revealed no published sequences significantly similar to the sequence of
      the fragment, precluding a prediction of the potential function of the sequence.
      The successful preparation of the near-isogenic Mi-virulent and avirulent lines
      laid a firm foundation for the further identification and isolation of virulence
      related genes in M. javanica.

PMID- 12182074
TI  - [Induction of non-disjunction of chromosome 8 by Tripterygium hypoglaucum (Levl.)
      Hutch in mouse sperm].
AB  - Fluorescence in situ hybridization (FISH) was employed to detect non-disjunction
      of chromosome 8 during meiosis in young adult male mice after treated by
      Tripterygium hypoglaucum(Levl.) Hutch(THH). The Kunming male mice were given
      THH(120 mg/kg, 240 mg/kg, 480 mg/kg) by abdominal cavity injection, and
      sacrificed 22 days sfter the treatment of THH. Epididymis sperm was used to make
      smear. FISH using bio-16-dUTP-labelled DNA probes specific for chromosome 8 was
      performed on epididymal sperm decondensed for 60 min each in 10 mmol/L DTT and 4
      mmol/L LIS. The aneuploidy frequencies of chromosome 8 were significantly higher
      than the solvent control (P < 0.001) in both 240 mg/kg group and 480 mg/kg group.
      The aneuploidy frequencies were not significantly different between the sperm in
      120 mg/kg group and the solvent control (P > 0.05). It is concluded that THH
      could induce non-disjunction of chromosome 8 in mouse sperm, and THH is a
      potential germinal aneugen in mammalian during the meiosis.

PMID- 12182075
TI  - [Establishment of segregating inbred strain of Yuyi hairless mice and its
      monitoring of genetic characteristics].
AB  - Using brother-sister inbreeding with forced heterozygosity to breed a new
      segregating inbred strain which carry mutant hairless gene. Then, genetic
      monitoring was conducted by the skin grafting test, coat color test and
      biochemical marker analysis, and its basic biological characteristics were
      studied with corresponding methods. The Results are that the Yuyi Hairless Mice
      (YYHL) with unique biological characteristics have been bred successfully and
      have progressed to 30th generation since 1991. Thirteen biochemical markers loci
      on nine chromosomes coding biochemical markers measured with electrophoresis were
      all homogenous. The skin grafting test showed that no dropping graft was found
      during 100 days after transplanting, implying the YYHL was of isohistogeneicity.
      Analysis of coat color genes indicated that the hair color of first generation
      hybrid crossed between YYHL and DBA/2 was all agouti suggesting that the coat
      color genes of the YYHL were homogenous. The gene type is AABBccDD. All these
      showed that the YYHL have been an inbred strain reaching the international
      standards.

PMID- 12182076
TI  - [Construction and homologous detection of a DNA plasmid library specific for Z
      chromosome of quail].
AB  - A simple method was used to adapt a standard light microscope for the collection
      of quail Z chromosomes from mitotic-metaphase spreads. The microisolated
      chromosomes were subjected to proteinase K treatment in a collection drop to
      release DNA, which was then amplified using a degenerate oligonucleotide-primed
      PCR (DOP-PCR) strategy. Size distributions of the PCR products were analyzed by
      agarose gel electrophoresis, and smears of DNA revealed that ranged in size from
      200-1 400 bp, without any evidence of preferential amplification. The second
      round PCR products were cloned into pBluescript plasmids to construct a Z
      chromosome-specific DNA library. The size range of the cloned inserts was 200-1
      400 bp. Using inserted fragments from the library as probes, chromosome painting
      was performed on quail chromosomes. The results showed that Z chromosomes of
      quail were completely covered by strong signals and there were little signals on
      other chromosomes. It was indicated that inserted DNA of the library was specific
      to the Z chromosome of quail. The library can be used as chromosome painting
      probe to detect conserved syntenic groups on the chromosomes of other related
      species and study mechanisms of sex-chromosomes evolution in birds.

PMID- 12182077
TI  - [Genetic analysis and molecular tagging of a gene for non-palea in rice].
AB  - The mutants involved in the development of floral organ are good material for
      understanding the molecular genetic mechanisms of floral development. A rice
      mutant, that lacks palea in its florets, was derived from a spontaneous mutation
      in an indica line, SAR III-93-369. Genetic analyses in three F2 populations from
      the mutant crossed with three rice varieties, Sheng 47, N625 and CDR22,
      respectively, showed that the mutant trait is controlled by a single recessive
      gene. In the F2 population from npa-1/Sheng47 the gene for the non-palea trait
      was mapped between two restriction fragment length polymorphism markers, C498 and
      RZ450, with distances of 7.5 cM and 2.4 cM, respectively. The tagged recessive
      non-palea gene is temporarily designated npa-1.

PMID- 12182078
TI  - [Analysis of gene loci and epistasis for drought tolerance in seedling stage of
      rice (Oryza sativa L.)].
AB  - Drought tolerance of rice is important because a considerable proportion of the
      world rice area is not irrigated and is prone to water deficit. In this study, an
      indica variety, Zhai Ye Qing 8 (ZYQ8), and a japonica variety, Jing Xi 17 (JX17),
      and their double haploid (DH) population were used for genetic study of drought
      tolerance. Water supply was stopped in seedling period for 15 days and then
      drought tolerance of the DH population and their parents were investigated.
      Mapping quantitative trait loci (QTLs) was undertaken base on the constructed
      molecular linkage map of this population. Two QTLs (qDR-5 and qDR-12) for drought
      tolerance were identified, they were in the region of GA41-GA257 on chromosome 5
      and RG457-Y12817R on chromosome 12, respectively. The tolerance alleles of both
      QTLs were from the indica parent, ZYQ8. In the meantime two genes for drought
      tolerance near GA257 and Y12817R were detected too by using Epistat software,
      that is in accordance with the result by using Mapmaker/QTL. In addition, three
      loci (RG541, G318 and G192 on chromosome 1, 4 and 8, respectively) were found
      interacting with GA257 by Epistat software, while one locus (CT234 on chromosome
      3) found interacting with Y12817R were also detected by Epistat software.

PMID- 12182079
TI  - [Physical mapping of the 45S rDNA and 5S rDNA to rice prometaphase chromosome].
AB  - Rice (Oryza sativa L.) is one of the most important cereal crops in the world.
      The chromosomes of rice are relatively small in size. With the help of
      fluorescence in situ hybridization (FISH), several rice DNAs have been localized
      on rice chromosomes. 45S rDNA and 5S rDNA are encoding sequences for ribosomal
      RNA synthesis. For detecting the chromosomes related to 45S rDNA and 5S rDNA, the
      digoxigenin-dUTP labeled probe DNA was probed to the prometaphase chromosomes
      which were prepared from the root tips harvested from an indica rice variety,
      Zhongxian 3037. For identification of the chromosomes, slides were stained with
      Giemsa before FISH. With the improved FISH protocol 45S rDNA was clearly detected
      on two pairs of chromosomes which are usually found to be attached to nucleolus.
      The signal size between two pairs of the chromosomes was different. According to
      the characteristics of the chromosomes, the chromosomes with bigger signal were
      chromosome 9 and the other pair were chromosome 10. They were also discriminated
      from arm ratio. The signals of 5S rDNA were relatively small but clear. According
      to the size and arm ratio of the chromosome with FISH signals, the 5S rDNA was
      mapped on the short arm of chromosome 11, very close to the centromere region.

PMID- 12182080
TI  - [Identification of molecular markers associated with rice root traits by
      correlation coefficient analysis].
AB  - After growing in nutrient solution for 10 days, 84 rice varieties were harvested
      and measured in maximum root length (MRL) and root dry weight (RDW) separately.
      Twenty-seven of them were selected as representative variety for correlated
      fragments screening with amplified fragment length polymorphism (AFLP) technique.
      After surveying with 15 pairs of AFLP primers, 7 fragments from 4 pairs of
      primers were identified having significant correlation with MRL or/and RDW based
      on correlation coefficient analysis. One of them, "T3P3f", was cloned and
      sequenced, and its specific primers (Z336) were designed for the regular PCR
      amplication. Further analysis in 84 rice varieties revealed that correlation
      coefficient between Z336 and MRL was -0.193, much closer to the significant level
      of 5%; as between Z336 and RDW was -0.391, over the significant level of 1%. For
      the trait expression, Z336 could explain the root trait difference of 3.7% for
      MRL and 15.3% for RDW, respectively. The result shows the marker Z336 might
      tightly link with a QTL that has the negative relation with RDW expression. With
      a double haploid (DH) population from a cross of ZYQ8 and JX17, Z336 was finally
      anchored on rice chromosome 11 with a linked marker of 9.4 cM.

PMID- 12182081
TI  - [Genetic variation of main restorer lines of hybrid rice in China was revealed by
      microsatellite markers].
AB  - A total of thirty-five restorer lines of hybrid rice (Oryza sativa L.) were
      analyzed by twenty-five SSR (simple sequence repeats) primer pairs, which
      disperse on 12 chromosomes in rice. Those primers detected 65 alleles among 35
      restorer lines of hybrid rice. Per primer pair detected 2.6 alleles on the
      average. PIC (polymorphism index content) values ranged from 0.206 to 0.682. PIC
      value is 0.414 on the average. The result from cluster analysis shows that hybrid
      rice restorer lines have abundant resource in China, but the genetic diversity is
      small and the genetic background is vulnerable among them. The utilization of
      rice heterosis was limited seriously.

PMID- 12182082
TI  - [Identification of blue grained wheat and its irradiation-mutated offsprings by
      genomic in situ hybridization (GISH)].
AB  - Transferring useful chromosome(s), chromosomal fragment(s) or genes from related
      species into common wheat (Triticum aestivum L.) is an effective method for
      improving wheat cultivars, and DNA:DNA in situ hybridization has been proven to
      be an effective method for directly demonstrating alien chromosome number and
      distribution in plant. In this study, genomic in situ hybridization (GISH) was
      used to identify the chromosomal constitutions of the blue-grained wheat Blue-58
      originated from distant hybridization between Triticum aestivum L. and Agropyron
      elongatum (Host) Beauv (2n = 10x = 70) and its irradiation-mutated offsprings.
      The results showed that, as previously reported, Blue-58 (2n = 42) was a
      substitution line in which a pair of 4D chromosomes of common wheat was
      substituted by a pair of 4E chromosomes from Agropyron elongatum. Mutation line
      LW004 might be a homozygous reciprocal translocation line in which two pair of
      chromosomes might be involved in the translocation event and it showed high
      efficiency in utilizing soil phosphorus in our field screening experiments.
      Mutation line LW43-3-4 was a blue monosomic line with 40 wheat chromosomes plus
      one 4E chromosome from Agropyron elongatum in its genome and its seeds showed
      light-blue color. Some other chromosome rearrangements and structure changes were
      also detected among the mutated offsprings through GISH, such as telomonosomic
      line (40 W + 1't4E) and a line with a chromosomal constitution of 39 W + 1'4E +
      1't4E. Our results indicated very clearly that it was the chromosome derived from
      Agropyron elongatum carried gene(s) responsible for the blue pigmentation in
      wheat grains and it was also illustrated from our results that the combination of
      effective methods for generating mutations at chromosomal level and convenient
      detection of these mutations played pivotal roles in creating materials for
      chromosome engineering and in breeding by means of chromosome engineering.

PMID- 12182083
TI  - [Factors affecting Agrobacterium tumefaciens-mediated transformation of wheat
      (Triticum aestivum L.)].
AB  - Immature embryos and embryo-derived calli from two cultivars of winter wheat
      (Triticum aestivum L.), BAU146 and BAU170, were transformed with three strains of
      Agrobacterium tumefaciens, AGL-1, EHA105 and LBA4404 harboring expression vector
      p3301 or pBTAaB. Both vectors contained bar gene and p3301 contained also gus
      gene with an intron. The highest explant survival rate and transformation
      efficiency was obtained when the bacterial cell density was OD600 1.0 with 1 h of
      infection incubation. Higher osmotic treatment of the explants before inoculation
      had a positive effect on transformation, while addition of acetosyringone showed
      ambiguous one, depending on the explant types and bacterium strains. The
      efficiencies of transformation and transgenic plant regeneration were varied
      greatly with the bacterium strain, receptor genotype, explant type and its age
      and physiological state. After optimizing these factors, a large number of PPT
      resistant calli and some of PPT-resistant plants were obtained. The resistant
      plantlet tested and 50% to 60% of the resistant calli were GUS-positive. The
      integration of foreign DNA into the genome of transgenic plants (3 out 6) was
      further confirmed by PCR and Southern Blot analysis.

PMID- 12182084
TI  - Molecular cloning, characterization and mapping of a rhodanese like gene in
      wheat.
AB  - To isolate genes related to resistance to Erysiphe graminis (Blumeria graminis)
      DC. f. sp. tritici in wheat (Triticum aestivum L.), differential display analysis
      was conducted for mRNA extracted from seedlings of a wheat-Haynaldia villosa
      6VS/6AL translocation line 92R137 that contains a powdery mildew resistance gene
      Pm21. A full-length cDNA sequence named TaTST (Triticum aestivum thiosulfate
      sulfurtransferase) homologous to the thiosulfate sulfurtransferase (rhodanese) in
      Datisca glomerata was isolated. Northern blot showed that the expression of TaTST
      was enhanced after infection with Erysiphe graminis. TaTST was mapped on the
      short arm of 6B chromosomes of wheat through Southern blot and GSP-PCR using
      Chinese Spring nullisomic/tetrasomic lines and ditelosomic lines. There is a
      homologue of TaTST on 6VS too.

PMID- 12182085
TI  - [Construction of physical map and polymorphism analysis of mtDNA region R from
      Mo17CMS-J of maize].
AB  - Total DNA from twenty-six CMS lines of maize under Mo17, 77 and W23 nuclear
      background were used for PCR amplification, including N, T, C, S four groups of
      cytoplasms. The primers was prefabricated according the sequence of R region
      published by Zebala (1997). Through these amplifications, mitochondrial DNA
      fragments were obtained from maize total DNA. Generally the results in one group
      are identical. And they are different from the others. The amplified fragments
      were sequenced and also give us much more information about the structure of
      mitochondrial genes that may lead to CMS. In order to isolate and identify the
      CMS genes, we developed a new platform to construct physical map of chromosome
      DNA by means of restriction enzyme double-digestion. The elongation of contigs is
      based on Southern hybridization. Having retrieved DNA from agarose gel after
      electrophoresis by beta-agarase, we labelled it with 32P-dCTP as a probe. We
      detected the positive clones in the gene library. Two contigs were revealed. And
      a restriction map covering 40 kb was constructed, including R region.

PMID- 12182086
TI  - [Cloning and characterization of cuticle degrading enzyme CDEP-1 from Beauveria
      bassiana].
AB  - Beauveria bassiana extracellular subtilisin-like serine endoprotease is a
      potential virulence factor by virtue of its activity against insect cuticles. A
      cDNA library was constructed using mRNA from mycelia of Beauveria bassiana grown
      on cuticle/chitin cultures. A cDNA clone of the protease, designated CDEP-1, was
      isolated from cDNA library. CDEP-1 contained an 1,134 bp ORF that predicted a
      protein of 377 amino acids with M(r) = 38,616 and PI = 8.302. The amino acid
      sequence of the gene shows 57.9%, 83.3% and 54.7% identity to Metarhizium
      nisopliae Pr1, Beauveria bassiana Pr1 and proteinase K, respectively. Southern
      analysis indicated that CDEP-1 was present as singly copy in Beauveria bassiana.

PMID- 12182087
TI  - Iatrogenesis imperfecta.

PMID- 12182088
TI  - An ominous message from a remote island.

PMID- 12182089
TI  - Alzheimer's disease in RI: perspectives in 2002.

PMID- 12182090
TI  - Agrin and microvascular damage in Alzheimer's disease.

PMID- 12182091
TI  - Dementia with Lewy bodies: a diagnostic and treatment challenge.
AB  - DLB demonstrates the pathological overlap between neurodegenerative disorders.
      Clinicians who work with the elderly need to be aware of the dramatic variability
      of symptoms in order to make an accurate diagnosis and treatment plan. There is
      much work to be done on the genetics and pathogenesis of DLB. More objectives
      diagnostic tests are needed, as are more controlled treatment trials for the
      specific symptoms of DLB.

PMID- 12182092
TI  - Medical treatment of Alzheimer's disease: past, present, and future.

PMID- 12182093
TI  - Behavioral issues in Alzheimer's disease.

PMID- 12182094
TI  - Quality of life in dementia.

PMID- 12182095
TI  - Judicial diagnosis. Guardianship and the incapacitated patient.

PMID- 12182096
TI  - Planning for trauma care in Rhode Island.

PMID- 12182097
TI  - Progress in the control of colorectal cancer in Rhode Island, 1987-2000.

PMID- 12182098
TI  - [Is it enough to use thyrotropin measurement alone as a standard screening of
      thyroid diseases?].

PMID- 12182099
TI  - [Etiopathogenesis of osteoarthritis].

PMID- 12182100
TI  - [Thoracoscopy].

PMID- 12182101
TI  - [Burn injuries in the burn care unit of Kuopio University Hospital 1994-2000].

PMID- 12182102
TI  - [Fetal breech presentation--an elective cesarean section or vaginal delivery?].

PMID- 12182103
TI  - [A primary aortocaval fistula: a rare complication of aortic aneurysm].

PMID- 12182104
TI  - [Dysphagia, cough and headache caused by Arnold-Chiari type I malformation].

PMID- 12182105
TI  - [Age and anticoagulant therapy].

PMID- 12182106
TI  - [Regularly appearing abdominal pain].

PMID- 12182107
TI  - [Overexploitation by Duodecim?].

PMID- 12182108
TI  - [Nothing is so sure than the unsure].

PMID- 12182109
TI  - IgM serum antibodies to human cytomegalovirus nonstructural gene products p52 and
      CM2(UL44 and UL57) are uniquely present in a subset of patients with chronic
      fatigue syndrome.
AB  - Human cytomegalovirus (HCMV) IgM serum antibodies to two nonstructural gene
      products UL44 and UL57 (p52 and CM2) were assayed in patients with the diagnosis
      of the chronic fatigue syndrome (CFS) according to criteria established by the US
      Centers for Disease Control and Prevention. A subset of 16 CFS patients
      demonstrated HCMV IgG, but no HCMV IgM serum antibodies to conformational
      structural HCMV antigens (designated, V). By convention, these findings are
      interpreted to indicate only a remote HCMV infection. However, HCMV IgM p52 and
      CM2 antibodies were uniquely present in these 16 CFS patients. Other CFS patients
      with similar HCMV (V) IgG antibodies (18 patients), non-fatigued HCMV (V) IgG
      positive control patients (18 patients), random HCMV (V) IgG-positive control
      patients from a clinical laboratory (26 patients), and non-fatigued HCMV (V) IgG
      negative control patients (15 patients) did not have HCMV, IgM p52 or CM2 serum
      antibodies (p < 0.05). Control HCMV (V) IgG-positive patients had no serum IgM
      HCMV (V) antibodies to conventional structural HCMV (V) antigen. Thus, 77 various
      control patients did not contain IgM p52 or CM2 serum antibodies. The presence of
      IgM p52 and/or CM2 HCMV serum antibodies in this subset of CSF-specific patients
      may detect incomplete HCMV multiplication in which a part of the HCMV protein
      coding content of the HCMV genome is processed, but remains unassembled. These
      findings suggest that the presence of HCMV IgM p52 and CM2 serum antibodies may
      be a specific diagnostic test for the diagnosis of a subset of CFS patients.
      Further, these data suggest an etiologic relationship for HCMV infection in this
      group of CFS patients.

PMID- 12182110
TI  - Species susceptibilities to chemical carcinogens: a critical appraisal of the
      roles of sex hormones (endocrine status) and nutritional influences.
AB  - The objective of the present evaluation was to assess the possible roles of the
      sex hormones (endocrine status), nutritional influences and other factors in
      regard to species susceptibilities to chemical carcinogens. By reviewing the
      experimental and epidemiological data, it was concluded that there are compelling
      indications, particularly in the fields of physiology and metabolism, to conclude
      the limited usefulness of the various animal species in sex hormone research. The
      findings allow only restricted inferences for the human species. On the other
      hand, as far as nutritional influences on cancer development are concerned,
      similar mechanisms operate with regard to high or low calorie, fat, protein and
      carbohydrate intakes in animals and humans. Consequently, the findings obtained
      in laboratory animals can be transmitted with some modifications to the human
      species. This assessment is the continuation of an earlier work, which appraised
      the roles of genetic and viral agents, concerning species susceptibilities to
      chemical carcinogens.

PMID- 12182111
TI  - Quantitative evaluation of the murine B16 melanoma tumor model after gene marking
      with an EGFP/Neo expressing retroviral vector.
AB  - Reliable evaluation of tumor growth in animal models depends upon accurate
      identification of all malignant cells in affected organs. An ideal tumor cell
      label is non-toxic, labels the cells in a population uniformly and does not
      affect their biological behavior. A good candidate for such a cell label is
      enhanced green fluorescence protein (EGFP). However, the stability of EGFP
      expression and the characteristics of EGFP-marked tumors cells in vivo have not
      yet been elucidated in detail. We here report that a B16 murine melanoma subline
      stably transduced with an EGFP/Neo encoding retroviral vector display the same
      growth patterns in vitro and in vivo as the parental cell line. Furthermore, the
      transduced cells were found to maintain the level of EGFP expression in vivo for
      at least 15 days. Thus, B16 malignant melanoma cells stably transduced with the
      gene for EGFP seem well suited for studies on tumor growth in mouse models.

PMID- 12182112
TI  - In vivo growth of mouse leukemia L1210 cells with metabolic alterations in the
      subunits of ribonucleotide reductase.
AB  - Mouse leukemia L1210 cells selected for resistance to drugs targeted specifically
      at each of the protein subunits of ribonucleotide reductase were studied for
      their ability to grow in vivo. The life-span of the mice injected with
      hydroxyurea-resistant L1210 cells, which have elevated levels of the mRNA and
      protein for the non-heme iron (NHI, R2) subunit of ribonucleotide reductase, was
      approximately twice that of the mice injected with equal numbers of the parental
      wild-type L1210 leukemia cells. The life-span of mice injected with the L1210
      cells that had alterations in the effector-binding subunit (EB, R1) was
      considerably shorter than the mice injected with the parental wild-type L1210
      cells. These results provide direct evidence that tumor cells with alterations in
      the properties of ribonucleotide reductase grow differently in vivo, with defined
      effects on the host mouse that cause either an increased survival time or a
      decreased survival time compared to the effects of wild-type L1210 leukemia cells
      on tumor-bearing mice.

PMID- 12182113
TI  - A role for effectors of cellular immunity in epimorphic regeneration of amphibian
      limbs.
AB  - Immune modulation of regeneration of amphibian appendages is suggested, but not
      proven, by previous studies. Earlier studies have not demonstrated effects of
      treatments on both epimorphic regeneration and immune responses or restoration of
      regeneration by specific reversal of immunomodulation. Cyclosporin A (CsA) and
      interleukin-2 (IL-2) were used in this study to demonstrate the effects of immune
      suppression and its reversal, on allograft rejection and forelimb regeneration.
      When administered alone, CsA suppressed rejection of skin allografts and induced
      a dose-dependent retardation of regeneration. IL-2, administered alone, did not
      affect allograft rejection or regeneration. However, when combined with CsA, IL-2
      abrogated or reversed effects of CsA on both allograft rejection and forelimb
      regeneration, in a dose-dependent manner. The selective focus of CsA's action and
      the ability of IL-2 to overcome and reverse these effects strongly suggest that T
      lymphocytes participate in or contribute to expression of epimorphic regeneration
      of amphibian appendages. Further studies are required to better characterize this
      role.

PMID- 12182114
TI  - Expression of inducible nitric oxide synthase during cisplatin-based chemotherapy
      for gastric cancer.
AB  - BACKGROUND: Nitric oxide (NO) has been reported to protect cells from apoptosis
      during chemotherapy. In this study, the protective role of inducible nitric oxide
      synthase (iNOS) against cisplatin (CDDP)-induced apoptosis was evaluated in a
      cell line and in patients with gastric cancer. MATERIALS AND METHODS: MKN-45
      cells were incubated with CDDP and the correlation between the occurrence of
      apoptotic cells (evaluated by flow cytometry) and the expression of iNOS
      messenger RNA (mRNA) in cells was analyzed. In 15 patients with advanced gastric
      cancer, CDDP-based preoperative chemotherapy was introduced. The expression
      levels of iNOS mRNA were compared between tumor samples before and after
      treatment with CDDP. Moreover, the iNOS protein expression and the percentage of
      apoptotic cancer cells (apoptotic index: AI) were analyzed immunohistochemically
      in 15 CDDP-treated tumors and in 50 untreated advanced gastric cancers. RESULTS:
      High AI was detected after 24 hours of treatment with high-dose CDDP in MKN-45,
      while the iNOS mRNA expression levels did not change before and after treatment.
      In 15 patients treated with CDDP, the percentage of iNOS mRNA-positive cases
      increased from 20% (pretreatment tumors) to 40% (resected tumors). However, the
      mean AI of iNOS-positive tumors was not different from that of iNOS-negative
      tumors. Also, in 50 untreated patients, iNOS protein expression did not correlate
      with the AIs of the tumors. CONCLUSION: Our results demonstrate that iNOS
      expression may not correlate with the occurrence of apoptosis during CDDP
      treatment in gastric cancer.

PMID- 12182115
TI  - Chronic colitis in Macaca fascicularis: similarities with chronic colitis in
      humans.
AB  - In recent years, a substantial number of macaques have died at the Southwest
      Foundation for Biomedical Research, USA, following protracted intractable
      diarrhea. The diarrhea could last for up to two years and occurred in infant,
      juvenile or young adult animals. The histopathological diagnosis at autopsy was
      chronic colitis. The histopathological subtype of chronic colitis is here
      assessed in a relatively large number of colonic specimens obtained at autopsy (n
      = 90). The colonic mucosa was well preserved for histological examination in 83
      of the 90 macaques. At review, various histological phenotypes of chronic colitis
      were found. Chronic lymphocytic-plasmacytic colitis occurred in 78.3% (65 out of
      83), chronic ulcerative colitis in 20.5% (17 out of 83) and Crohn's colitis in
      1.2% (1 out of 83). In macaques, some histological phenotypes of chronic colitis
      (ulcerative and Crohn's colitis) closely mimic chronic colitis in humans. The
      awareness that chronic colitis in macaques is not one disease but a series of
      chronic inflammatory changes, with common clinical symptoms and similar gross
      appearances, may lead to the correct histological diagnosis of the subtype of the
      disease.

PMID- 12182116
TI  - Carcinoid tumor originating in a horseshoe kidney.
AB  - An atypical carcinoid tumor originating in the horseshoe kidney of a 39-year-old
      man is reported. The tumor showed cytological atypia, increased mitotic rate and
      histological signs of mucinous differentiation and osseous metaplasia. Even
      though there were distant metastases, the patient survived partial nephrectomy
      including resection of the primary tumor for four years. The review of literature
      shows that carcinoid tumors originate some 60 to 85 times more often in horseshoe
      kidneys than in normal kidneys. The clinical course of renal carcinoid tumors is
      highly variable.

PMID- 12182117
TI  - Oral administration of 5-methoxypsoralen affects the distribution and metabolism
      of 2-aminofluorene in Sprague-Dawley rats.
AB  - BACKGROUND: The effects of 5-methoxypsoralen (5-MOP) on the distribution and
      metabolism of chemical carcinogens such as 2-aminofluorene (AF) has not been
      previously reported. In this study, the influences of 5-MOP on the metabolism of
      AF in Sprague-Dawley (SD) rats were investigated. MATERIALS AND METHODS: After
      receiving 5-MOP in 24 hours, AF was introduced into each animal by gastric
      intubation. After 12, 24, 48 and 72 hours the urine, feces, and cytosol of the
      liver, kidneys, stomach, colon, bladder and blood of rats were collected and
      assayed for AF and its metabolites by HPLC. RESULTS: Compared to the control
      regimen, 5-MOP caused an increase of the metabolites excreted in urine and feces.
      The largest dose of metabolites were excreted between 48-72 hours. The major
      metabolite excreted in the urine was 9-hydroxy-AAF (9-OH-AAF) and in the feces
      was 7-hydroxy-AAF (7-OH-AAF). There was no time-effect for the tissues, and the
      liver was the main target organ for the AF and its metabolites. The major
      residual metabolite of AF in the liver, kidneys, stomach, colon and bladder was 7
      OH-AAF. In blood it was 9-OH-AAF. The bladder had the lowest metabolic residue in
      tissues, and blood played the role of transportation but was not the target
      organ. 5-MOP decreased the concentration of AF and its residual metabolites of
      liver, stomach, kidneys, bladder and blood at various times. CONCLUSION: 5-MOP
      increased the metabolism of AF in order to transform to ring-hydroxylated
      metabolites and increased excretion of the ring-hydroxylated metabolites,
      therefore decreasing AF and its residual metabolites in vivo. Although 5-MOP was
      shown to be an inhibitor of CYP 2A6 and CYP 2B1, somehow it causes an increase of
      activity in AF metabolism in vivo; it induces more CYPs involved in the
      metabolism of AF.

PMID- 12182118
TI  - Developmental abnormalities induced by X-irradiation in p53 deficient mice.
AB  - In order to assess the influence of p53 inactivation on radiation-induced
      developmental effects, male mice heterozygous for the wild-type p53 allele
      (mimicking the human Li-Fraumeni syndrome) were crossed with C57BL females, and
      their heterozygous p53+/- progeny were mated with each other to obtain p53+/-,
      p53-/- and p53+/+ embryos. Pregnant females were X-irradiated with 0.5 Gy on days
      1 (pre-implantation period), 8 or 11 (organogenesis period) of gestation.
      Dissection of the pregnant females occurred on day 19 of gestation. The p53
      genotype of the foetuses was determined by PCR from small pieces of soft tissues.
      Exencephaly was the only external malformation found in the control group. It
      affected essentially p53-/- female foetuses. A number of p53+/- and p53+/-
      control foetuses also showed dwarfism, or underdevelopment. In the group
      irradiated on day 1, the frequency of abnormal foetuses was, paradoxically, lower
      than that found in the control group. As in that group, exencephaly and dwarfism
      constituted the only anomalies that were found. Exencephaly affected only
      homozygous p53-/- females, while dwarfism concerned either p53-/- or p53+/-
      foetuses, with a majority of females. Irradiation on day 8 of gestation induced a
      significant increase in the frequency of abnormal foetuses, compared to the
      control group. Various malformations were observed in addition to exencephaly,
      including gastroschisis, polydactyly, cephalic oedema and cleft palate. All
      malformed foetuses were either homozygous p53-/- or heterozygous p53+/- while
      most affected foetuses were females, as was the case for dwarf individuals.
      Irradiation on day 11 did not cause an increase in the frequency of abnormal
      foetuses, in comparison with the controls. However, a large spectrum of external
      malformations was again noticed, as in the group irradiated on day 8. All
      affected foetuses were homozygous p53-/- and there were slightly more abnormal
      females than males (3 out of 5). No dwarfs were found in this group. Overall,
      these results confirm the importance of the p53 tumour-suppressor protein for
      normal embryonic development. They clearly show that homozygous p53-/- (or
      heterozygous p53+/- to a lesser extent) foetuses are more at risk for radiation
      induction of external malformations during the organogenesis period, and that the
      risk of developing such malformations is much higher for females than for males.
      In contrast to results published very recently by others, we found that malformed
      foetuses resulting from an X-irradiation with a low-dose during the highly
      sensitive period of gastrulation are able to survive to birth.

PMID- 12182119
TI  - Modeling the effects of genetic factors on late-onset diseases in cohort studies.
AB  - Many late-onset diseases are caused by what appears to be a combination of a
      genetic predisposition to disease and environmental factors. The use of existing
      cohort studies provides an opportunity to infer genetic predisposition to disease
      on a representative sample of a study population, now that many such studies are
      gathering genetic information on the participants. One feature to using existing
      cohorts is that subjects may be censored due to death prior to genetic sampling,
      thereby adding a layer of complexity to the analysis. We develop a statistical
      framework to infer parameters of a latent variables model for disease onset. The
      latent variables model describes the role of genetic and modifiable risk factors
      on the onset ages of multiple diseases, and accounts for right-censoring of
      disease onset ages. The framework also allows for missing genetic information by
      inferring a subject's unknown genotype through appropriately incorporated
      covariate information. The model is applied to data gathered in the Framingham
      Heart Study for measuring the effect of different Apo-E genotypes on the
      occurrence of various cardiovascular disease events.

PMID- 12182120
TI  - Smooth conditional distribution function and quantiles under random censorship.
AB  - We consider a nonparametric random design regression model in which the response
      variable is possibly right censored. The aim of this paper is to estimate the
      conditional distribution function and the conditional alpha-quantile of the
      response variable. We restrict attention to the case where the response variable
      as well as the explanatory variable are unidimensional and continuous. We propose
      and discuss two classes of estimators which are smooth with respect to the
      response variable as well as to the covariate. Some simulations demonstrate that
      the new methods have better mean square error performances than the generalized
      Kaplan-Meier estimator introduced by Beran (1981) and considered in the
      literature by Dabrowska (1989, 1992) and Gonzalez-Manteiga and Cadarso-Suarez
      (1994).

PMID- 12182121
TI  - The additive nonparametric and semiparametric Aalen model as the rate function
      for a counting process.
AB  - We use the additive risk model of Aalen (Aalen, 1980) as a model for the rate of
      a counting process. Rather than specifying the intensity, that is the
      instantaneous probability of an event conditional on the entire history of the
      relevant covariates and counting processes, we present a model for the rate
      function, i.e., the instantaneous probability of an event conditional on only a
      selected set of covariates. When the rate function for the counting process is of
      Aalen form we show that the usual Aalen estimator can be used and gives almost
      unbiased estimates. The usual martingale based variance estimator is incorrect
      and an alternative estimator should be used. We also consider the semi-parametric
      version of the Aalen model as a rate model (McKeague and Sasieni, 1994) and show
      that the standard errors that are computed based on an assumption of intensities
      are incorrect and give a different estimator. Finally, we introduce and implement
      a test-statistic for the hypothesis of a time-constant effect in both the non
      parametric and semi-parametric model. A small simulation study was performed to
      evaluate the performance of the new estimator of the standard error.

PMID- 12182122
TI  - Semiparametric inference methods for general time scale models.
AB  - In this paper we consider semiparametric inference methods for the time scale
      parameters in general time scale models (Oakes, 1995; Duchesne and Lawless,
      2000). We use the results of Robins and Tsiatis (1992) and Lin and Ying (1995) to
      derive a rank-based estimator that is more efficient and robust than the
      traditional minimum coefficient of variation (min CV) estimator of Kordonsky and
      Gerstbakh (1993) for many underlying models. Moreover, our estimator can readily
      handle censored samples, which is not the case with the min CV method.

PMID- 12182123
TI  - Generalized supremum tests for the equality of cause specific hazard rates.
AB  - In this paper we propose two new classes of asymptotically distribution-free
      Renyi-type tests for testing the equality of two risks in a competing risk model
      with possible censoring. This work extends the work of Aly, Kochar and McKeague
      [1994, Journal of American Statistical Association, 89, 994-999] and many of the
      existing tests for this problem belong to these newly proposed classes. The
      asymptotic properties of the proposed tests are investigated. Simulation studies
      are done to compare the performance with existing tests. A competing risks data
      set is analyzed to demonstrate the usefulness of the procedure.

PMID- 12182124
TI  - A minimum distance estimation approach to the two-sample location-scale problem.
AB  - As reported by Kalbfleisch and Prentice (1980), the generalized Wilcoxon test
      fails to detect a difference between the lifetime distributions of the male and
      female mice died from Thymic Leukemia. This failure is a result of the test's
      inability to detect a distributional difference when a location shift and a scale
      change exist simultaneously. In this article, we propose an estimator based on
      the minimization of an average distance between two independent quantile
      processes under a location-scale model. Large sample inference on the proposed
      estimator, with possible right-censorship, is discussed. The mouse leukemia data
      are used as an example for illustration purpose.

PMID- 12182125
TI  - Proceedings from the tenth course on accelerator radiation protection.
      International School of Radiation Damage and Protection. Erice, Sicily. October 2
      9, 2001.

PMID- 12182127
TI  - Proceedings of the Indo-US Workshop on Nutrition and Health of Women, Infants,
      and Children. Hyderabad, India. February 10-12, 2000.

PMID- 12182126
TI  - Commentary on "Community mental health care for women with severe mental illness
      who are parents" - The tragedy of missed opportunities: of missed opportunities:
      What providers can do.
AB  - Women and men who meet criteria for psychiatric disorder are likely to be
      parents. Many go undiagnosed and untreated, putting themselves and their children
      at risk of poor outcomes. Adults with mental illness may fear disclosing their
      status as parents; providers may not ask. Practices can be modified to promote
      the well being of parents with mental illness and their children.

PMID- 12182128
TI  - Food- and water-borne parasitic zoonoses in the 21st Century. Proceedings of the
      3rd Seminar on Food-Borne Parasitic Zoonoses in the 21st Century. Bangkok,
      Thailand. December 6-8, 2000.

PMID- 12182129
TI  - CURE: A panacea for all ills?

PMID- 12182130
TI  - Proceedings of the International Conference on Dietary Factors: Cancer Causes and
      Prevention. Vienna, Austria. February 14-17, 2001.

PMID- 12182131
TI  - Therapy for the treatment-experienced patient.

PMID- 12182132
TI  - Current concepts in HIV-associated nephropathy.

PMID- 12182133
TI  - Highlights from the 13th meeting of the International Society for Sexually
      Transmitted Diseases Research.

PMID- 12182134
TI  - Nevirapine reduces perinatal HIV transmission.

PMID- 12182135
TI  - Antiretroviral therapy.

PMID- 12182136
TI  - Update on opportunistic infections.

PMID- 12182137
TI  - Toxicity of antiretroviral agents.

PMID- 12182138
TI  - HIV outcomes: natural history of HIV and economic impact.

PMID- 12182139
TI  - Second national AIDS malignancy conference.

PMID- 12182140
TI  - ACOG committee opinion. "Scheduled cesarean delivery and the prevention of
      vertical transmission of HIV infection" [ACOG committee opinion #219, August
      1999].

PMID- 12182141
TI  - Antiretroviral therapy in naive patients.

PMID- 12182142
TI  - Management of the treatment experienced patient.

PMID- 12182143
TI  - Responding to HIV treatment side effects and residual symptoms.

PMID- 12182144
TI  - Editorial: symptoms of living with HIV.

PMID- 12182145
TI  - HAART breaks: structured treatment interruptions.

PMID- 12182146
TI  - Predicting type 1 diabetes using autoantibodies: the latest results from the
      diabetes autoantibody standardization program.

PMID- 12182147
TI  - Papers from the Japanese Surgical Society presented at the 63rd Annual Meeting of
      the Society of University Surgeons. Honolulu, Hawaii, USA. February 14-16, 2002.

PMID- 12182148
TI  - [Male reproductive capacity and its investigation. 1952].

PMID- 12182149
TI  - [Basement membrane laminin in head and neck squamous cell carcinoma and its
      significance in therapy].

PMID- 12182150
TI  - [Physiopathology of allergic rhinitis in children and its treatment].

PMID- 12182151
TI  - Sharp packaging.

PMID- 12182152
TI  - Sezary syndrome.

PMID- 12182153
TI  - A familiar asthma spacer for inhalation induction.

PMID- 12182155
TI  - The Big Mac test.

PMID- 12182157
TI  - Bibliography. Current world literature. Degenerative diseases.

PMID- 12182156
TI  - Seminal plasma induces programmed cell death in cultured peripheral blood
      mononuclear cells.
AB  - Immunosuppressive properties of seminal plasma inhibit the recovery of infectious
      HIV from semen, and led to the view early in the pandemic that semen HIV was
      transmitted principally by infected semen cells. More recent studies have
      revealed significant titers of HIV RNA in seminal plasma, however, even from men
      receiving successful antiviral therapy. Thus, studies of infectious HIV in
      seminal plasma are important to understanding sexual transmission and response to
      therapy. The present studies were undertaken to determine whether seminal plasma
      immunosuppression is mediated by the induction of programmed cell death (PCD).
      Peripheral blood mononuclear cells (PBMCs) were cultured without or with
      phytohemagglutinin and seminal plasma from normal donors, or men postvasectomy,
      or seminal vesicle protein collected at surgery. PBMC survival was measured at 3,
      6, and 18 hr of culture; cells were examined for evidence of PCD by uptake of the
      fluorescent dye YO-PRO, and for fragmented nuclear DNA by the TUNEL assay.
      Approximately 90% of PBMCs cultured with seminal plasma from intact or
      vasectomized men were lost during 18 hr of culture; seminal vesicle protein did
      not induce cell loss. PCD assays were positive for PBMCs exposed to the seminal
      plasma, and negative for PBMCs cultured with seminal vesicle protein. Serum was
      not required for PCD induction. A 3-hr pulse with seminal plasma was sufficient
      to initiate PCD. These findings indicate that PCD induction accounts for the
      cytotoxic properties of semen, that the PCD is not the result of semen amine
      oxidases, and either that substances produced by seminal vesicles only at
      ejaculation, or by the prostate, are responsible for PCD induction.

PMID- 12182158
TI  - Bibliography. Current world literature. Movement disorders.

PMID- 12182160
TI  - The Royal Army Medical College. 1904.

PMID- 12182159
TI  - Inhibitory effects of 14-membered ring macrolide antibiotics on bleomycin-induced
      acute lung injury.
AB  - 14-membered ring macrolides have been reported to have anti-inflammatory effects
      and to decrease neutrophil infiltration into the airways in chronic lower
      respiratory tract diseases. This study investigated the potential inhibitory
      effects of macrolide antibiotics on bleomycin-induced acute lung injury. Four
      drugs were studied: two 14-membered ring macrolides, clarithromycin (CAM) and
      roxithromycin (RXM); a 15-membered ring macrolide, azithromycin (AZM); and a 16
      membered ring macrolide, josamycin (JM). Their effects were compared with
      macrolide untreated, pretreated, and post-treated groups. An acute lung injury
      was inhibited by pretreatment with CAM or RXM, which significantly ameliorated
      the bleomycin-induced increases in the total cell and neutrophil counts in
      bronchoalveolar lavage (BAL) fluids and the wet lung weight. The pretreatment
      with CAM or RXM also suppressed inflammatory cell infiltration and interstitial
      lung edema in the histopathological study. These inhibitory effects were
      associated with a decreased KC concentration in the BAL fluid and a decreased
      number of apoptotic cells in the lungs. Posttreatment with CAM or RXM had no
      marked inhibitory effects. Pretreatment with AZM was much less effective, and JM
      showed no inhibitory effects. These findings suggest that 14-membered ring
      macrolides have different effects on inflammatory lung disease than 15- and 16
      membered ring macrolides and may be therapeutic agents for acute lung injury and
      pulmonary fibrosis.

PMID- 12182161
TI  - Understanding sexual activity defined in the HEDIS measure of screening young
      women for Chlamydia trachomatis.
AB  - BACKGROUND: Periodic screening of sexually active young women for Chlamydia
      trachomatis is widely recommended and is now monitored in the Health Plan
      Employer Data and Information Set (HEDIS). Because little is known about how well
      the HEDIS measure identifies sexually active women eligible for screening, rates
      of sexual activity as defined by the measure's specifications were compared with
      those derived from self-reported sexual behavior and use of sexual health
      services among privately insured women. METHODS: Using the 1996 MarketScan claims
      data for privately insured women aged 15-25 years, a measure of sexual activity
      based on the HEDIS specifications for sexual activity was calculated, that is,
      claims for Pap tests and pelvic examinations, contraceptive services, pregnancy
      related service, and screening and treatment for sexually transmitted diseases.
      RESULTS: For privately insured women 15-25 years of age, the sexual activity rate
      was estimated to be 27% based on the HEDIS algorithm using the MarketScan claims
      data and 60% based on self-reported sexual behavior or 62% based on self-reported
      use of sexual health services using the 1995 National Survey of Family Growth
      (NSFG) data. DISCUSSION: Among young, privately insured women, use of claims
      specified by HEDIS classifies a smaller proportion of young women as sexually
      active than does use of self-reported survey data on sexual behavior or use of
      sexual health services. If HEDIS continues to rely on claims data because it is
      easier or less costly to collect and analyze than survey data, users of this
      performance measure should be aware that it may underestimate the number of women
      who are eligible for this screening benefit.

PMID- 12182163
TI  - From the Centers for Disease Control and Prevention. Multistate outbreak of
      Escherichia coli O157:H7 infections associated with eating ground beef--United
      States, June-July 2002.

PMID- 12182162
TI  - Relationship of family functioning to progress in a post-acute rehabilitation
      programme following traumatic brain injury.
AB  - PRIMARY OBJECTIVE: To investigate the relationship of family functioning to
      patients' progress in a post-acute TBI rehabilitation programme. RESEARCH DESIGN:
      Cohort study investigating predictors of change from admission to follow-up.
      METHODS AND PROCEDURES: Caregivers of 37 persons with severe TBI consecutively
      admitted to a residential post-acute rehabilitation facility completed the Family
      Assessment Device (FAD) within a few weeks of admission. The Disability Rating
      Scale (DRS) was completed upon admission and approximately 1 month after
      discharge. FAD scores were used to predict DRS change scores after controlling
      for injury severity, admit FAD scores, and time from admission to follow-up. MAIN
      OUTCOMES AND RESULTS: Persons with unhealthy family functioning showed less
      improvement on DRS total, level of functioning (LOF), and employability (EMP)
      scores. CONCLUSIONS: The results emphasize that family functioning is an
      important variable to include in future models predicting rehabilitation outcome,
      and the importance of family intervention as part of the rehabilitation process.

PMID- 12182164
TI  - From the Centers for Disease Control and Prevention. Update: AIDS--United States,
      2000.

PMID- 12182166
TI  - Brain death worldwide: accepted fact but no global consensus in diagnostic
      criteria.

PMID- 12182165
TI  - The neurogenetics of mucolipidosis type IV.
AB  - BACKGROUND: Mucolipidosis type IV (MLIV) is an autosomal recessive disease caused
      by mutations in the MCOLN1 gene that codes for mucolipin, a member of the
      transient receptor potential (TRP) gene family. OBJECTIVE: To comprehensively
      characterize the clinical and genetic abnormalities of MLIV. METHODS: Twenty
      eight patients with MLIV, aged 2 to 25 years, were studied. Ten returned for
      follow-up every 1 to 2 years for up to 5 years. Standard clinical, neuroimaging,
      neurophysiologic, and genetic techniques were used. RESULTS: All patients had
      varying degrees of corneal clouding, with progressive optic atrophy and retinal
      dystrophy. Twenty-three patients had severe motor and mental impairment. Motor
      function deteriorated in three patients and remained stable in the rest. All had
      a constitutive achlorhydria with elevated plasma gastrin level, and 12 had iron
      deficiency or anemia. Head MRI showed consistent characteristic findings of a
      thin corpus callosum and remained unchanged during the follow-up period.
      Prominent abnormalities of speech, hand usage, and swallowing were also noted.
      Mutations in the MCOLN1 gene were present in all patients. Correlation of the
      genotype with the neurologic handicap and corpus callosum dysplasia was found.
      CONCLUSIONS: MLIV is both a developmental and a degenerative disorder. The
      presentation as a cerebral palsy-like encephalopathy may delay diagnosis.

PMID- 12182167
TI  - Brain death worldwide: accepted fact but no global consensus in diagnostic
      criteria.

PMID- 12182168
TI  - Brain death worldwide: accepted fact but no global consensus in diagnostic
      criteria.

PMID- 12182170
TI  - Study outlines key factors in successful beta-blocker use.

PMID- 12182169
TI  - Brain death worldwide: accepted fact but no global consensus in diagnostic
      criteria.

PMID- 12182171
TI  - New tactics shorten hospital stays for prostate patients.

PMID- 12182172
TI  - New medication recommended for Parkinson's disease.

PMID- 12182173
TI  - A short history of the urology in Hungary.

PMID- 12182174
TI  - [The "hospital review" in 1865: the first journal for hospital service in
      Hungary].
AB  - This article is a concise history of the first Hungarian journal for hospital
      medicine published in Pozsony (Bratislava, Pressburg) from the year 1865. The
      editorial board of the Korhazi Szemle (Hospital Review) consisting of young
      physicians (Zlamal, Gotthard, Kanka) attempted to give a complete overview on
      Hungarian hospital research, including new ways of therapies and hospital
      statistics as well. Analysing the publications of the journal author concludes,
      that the hospital of Pozsony (Bratislava) founded in 1864 represented a rather
      high niveau of healing. The first tracheotomies, and the first histologic tests
      have been performed here in the region.

PMID- 12182175
TI  - [Birth control in antiquity].
AB  - Challenges of the overpopulation has been handled by two different ways by
      ancient Greeks: on the level of the individual and on that of the community
      respectively. Regarding the so-called micro-social strategies various preventive
      methods (getting married late, contraception, homosexuality, prostitution,
      zoophily and the one-child system) but also those of correctional methods were
      used as well: abortion, killing the new-born or selling him or her as a slave.
      The author, who is a well-known researcher of the polis system, gives an overview
      of all these methods. He focuses-by the help of contemporary texts-on the problem
      of putting out the child, single-child system, late marriage, contraception and
      abortion.

PMID- 12182176
TI  - [The role of the scientific societies in the development of the Hungarian medical
      literature between 1867 and 1914].

PMID- 12182177
TI  - Who lives where? British anti-malaria policy in Southern-Nigeria (1899-1912).

PMID- 12182178
TI  - [The history of the so called "Shortened University Courses". The medical faculty
      of the Royal Hungarian University of Sciences in Breslau and Halle 1944-45].
AB  - On the autumn of 1944, when the Soviet troops entered Hungary and quickly pushed
      toward Budapest, the government was taken over by Hungarian Nazis - backed by the
      SS and the Wehrmacht. The new government attempted to evacuate all public
      administration including ministries, various offices, institutions of higher
      education, the gold reserve, the Crown etc. and equipment to Germany. A
      governmental decree located as a centre of Hungarian medical education Halle an
      der Saale. The students of the recently organized "shortened courses" were forced
      to leave their homeland and finish their studies in the Reich. Author - being a
      witness and victim of these events - gives a detailed and vivid report of the
      troubles, circumstances and losses of the Hungarian community in Germany. Later
      on he discusses also the offences, and unfounded accusations students had to
      suffer, when retiring home. The article has been the first one describing these
      events from viewpoint of the medical students, for almost sixty years.

PMID- 12182179
TI  - The memory of today in the history of medicine.

PMID- 12182180
TI  - [The first decades of pharmaceutical training at the Royal Hungarian University
      in the XVIIIth century].
AB  - This is the second part of the author's former article; the previous one was
      published in the last issue of our journal. The author gives an overview on the
      education of pharmacists in 18th-century Hungary. She attempts to provide a
      complete list of the sources of medical and pharmaceutical education, with a
      special regard on subjects lacking any textbook published in Hungary at that
      time. Based on the analysis of hand-written and archival data author concludes
      that students during their courses borrowed the required exsiccated material or
      manuscripts and even the herbal items from the University itself. Author calls
      our attention to the hitherto neglected fact, that the possibility of acquiring
      botanical knowledge was actually given at the University, while former researches
      emphasized only the difficulties. Even the library of the university at Buda and
      Pest possessed a rather valuable material. Author concludes, that the
      pharmaceutical education in Hungary presented the average level of the age.

PMID- 12182181
TI  - n-3 fatty acids and the risk of sudden death.

PMID- 12182182
TI  - n-3 fatty acids and the risk of sudden death.

PMID- 12182183
TI  - n-3 fatty acids and the risk of sudden death.

PMID- 12182184
TI  - Treatment preferences of seriously ill patients.

PMID- 12182185
TI  - Treatment preferences of seriously ill patients.

PMID- 12182186
TI  - Treatment preferences of seriously ill patients.

PMID- 12182187
TI  - Medical events during airline flights.

PMID- 12182188
TI  - Medical events during airline flights.

PMID- 12182189
TI  - Medical events during airline flights.

PMID- 12182190
TI  - Medical events during airline flights.

PMID- 12182191
TI  - Medical events during airline flights.

PMID- 12182192
TI  - Framework Convention on Tobacco Control.

PMID- 12182193
TI  - Framework Convention on Tobacco Control.

PMID- 12182194
TI  - Applying positive psychology in the study of extreme environments.

PMID- 12182195
TI  - Interrelations between the small isolated groups with homogeneous and
      heterogeneous composition.
AB  - Increase in the heterogeneity of a space crew's composition (cultural and gender
      differences) is a risk factor that can negatively influence the formation of a
      cohesive crew, which depends on a common way of perceiving one's social
      environment, goals and values. Method. Three groups working in isolation from 110
      to 240 days, all with different cultural and gender composition were analysed
      using a modification of Kelly's repertory grid technique during a space
      simulation at the Institute for Biomedical Problems, Moscow. Subjects assessed
      themselves and each other monthly. Results. National Russian and international
      groups failed to create a single cohesive crew. Members of both groups considered
      people from their group as "us" and their neighbours as "them". Their relations
      became more negative during the mission, with attitudes changing from neutral to
      poor. Subjects began to perceive each other as "different and distant". Cultural
      and language differences prevented national (Russian) and international groups
      from forming a common understanding of behavioural rules and establishing close
      emotional contacts. Conclusions. Differences in perception of the interpersonal
      environment, group goals and values in national and international groups hindered
      the formation of a joint cohesive crew.

PMID- 12182196
TI  - Entropy generation method to quantify thermal comfort.
AB  - The present paper presents a thermodynamic approach to assess the quality of
      human-thermal environment interaction and quantify thermal comfort. The approach
      involves development of entropy generation term by applying second law of
      thermodynamics to the combined human-environment system. The entropy generation
      term combines both human thermal physiological responses and thermal
      environmental variables to provide an objective measure of thermal comfort. The
      original concepts and definitions form the basis for establishing the
      mathematical relationship between thermal comfort and entropy generation term. As
      a result of logic and deterministic approach, an Objective Thermal Comfort Index
      (OTCI) is defined and established as a function of entropy generation. In order
      to verify the entropy-based thermal comfort model, human thermal physiological
      responses due to changes in ambient conditions are simulated using a well
      established and validated human thermal model developed at the Institute of
      Environmental Research of Kansas State University (KSU). The finite element based
      KSU human thermal computer model is being utilized as a "Computational
      Environmental Chamber" to conduct series of simulations to examine the human
      thermal responses to different environmental conditions. The output from the
      simulation, which include human thermal responses and input data consisting of
      environmental conditions are fed into the thermal comfort model. Continuous
      monitoring of thermal comfort in comfortable and extreme environmental conditions
      is demonstrated. The Objective Thermal Comfort values obtained from the entropy
      based model are validated against regression based Predicted Mean Vote (PMV)
      values. Using the corresponding air temperatures and vapor pressures that were
      used in the computer simulation in the regression equation generates the PMV
      values. The preliminary results indicate that the OTCI and PMV values correlate
      well under ideal conditions. However, an experimental study is needed in the
      future to fully establish the validity of the OTCI formula and the model. One of
      the practical applications of this index is that could it be integrated in
      thermal control systems to develop human-centered environmental control systems
      for potential use in aircraft, mass transit vehicles, intelligent building
      systems, and space vehicles.

PMID- 12182197
TI  - Critical path plan for food and nutrition research required for planetary
      exploration missions.
AB  - In preparation for future planetary exploration, NASA-Johnson Space Center has
      developed a critical path plan for food and nutrition research needs. The plan
      highlights the risk factors pertaining to food and nutrition associated with
      exposure to the space flight environment as well as the possible consequences if
      no corrective measures are implemented. Included in the plan are the initiating
      events such as microgravity, remote environment and mission duration, which
      obviously impact the risk factors. The plan includes points of intervention where
      mitigating factors can be implemented to avoid outcomes such as malnutrition and
      unsafe foods. Physiological changes induced by lack of gravity, as well as
      increased exposure to radiation, may alter nutrient bio-availability, and/or
      nutrient requirements. An inadequate food system, whether due to technical
      limitations or nutritional shortcomings, can result in serious consequences.
      Additionally, microbial and chemical food contamination or psychological factors
      such as depression may lead to insufficient food intake. Critical questions
      define areas where further research is required to eliminate or ameliorate the
      risk from each of those factors. These questions delineate priorities for NASA
      food and nutrition research for planetary exploration missions.

PMID- 12182198
TI  - Psychology keeps astronauts well grounded: structures that psychologists put in
      place are critical to an astronaut's success.

PMID- 12182199
TI  - Aerospace clinical psychology and its role in serving practitioners of hazardous
      activities.

PMID- 12182200
TI  - Some problems of group interaction in prolonged space flights.
AB  - The objective of this paper is to describe psychological phenomena which has
      developed in the course of inter- and intragroup interaction in space. Several
      objective reasons are stressed which comprise the basis of the formation of the
      majority of the psychological phenomena. The authors also discuss prediction of
      these phenomena, namely, can they occur on the International Space Station (ISS)
      and what countermeasures will prevent them. In the analysis, the authors rely on
      the practice of prolonged spaceflight (PSF) psychological support in Russia;
      preliminary results of several flights within the Mir/NASA project; the personal
      experience of cosmonaut Valery V. Polyakov; and data gained during prolonged
      studies simulating PSF conditions (isolation, microgravity, etc.).

PMID- 12182201
TI  - Human performance during spaceflight.

PMID- 12182202
TI  - EPR adoption and dual record maintenance in the U.S.: assessing variation in
      medical systems infrastructure.
AB  - The growing adoption of evidence-based medicine in the United States is acting to
      cause fundamental changes in the delivery of healthcare management services. With
      the increasing incorporation of electronic patient records (EPRs) into the day-to
      day practice of medicine, it necessitates greater dependence on adequate
      functioning of such resources, as they become more frequently used as a clinical
      complement in the practice of medicine. Assessing the patterns of adoption of
      EPRs is likewise of increasing importance, with the recent imposition of uniform
      government data collection and management requirements. The medium of data
      storage and maintenance within many organizations is a critical factor in the
      ultimate delivery of service, with a like need for an integrated, designated
      medium for the management of data becoming paramount. This study examines, on a
      nationwide basis, variation in reported adoption of EPRs within U.S. healthcare
      organizations, and the related maintenance of dual electronic/paper record
      systems.

PMID- 12182203
TI  - Regional variation in medical systems data: influences on upcoding.
AB  - Attempts to minimize over-reimbursement to health care providers have resulted in
      highly publicized prosecution of health care providers and provider
      organizations. Such prosecution has led many to propose that upcoding influences
      exerted upon health care information managers would largely disappear, both
      within and external to the provider organization. This study seeks to examine the
      degree of both intra- and extraorganizational influences on reimbursement
      optimizing practices through a national survey of accredited health information
      managers. Results suggest that significant upcoding influence continues to occur
      within organizations, despite the risk of severe counterfraud penalties designed
      to eliminate such practices. We examine variation in intra- and
      extraorganizational optimizing influences, finding such influence was found to
      exist both within and external to the provider organization. We also examine how
      optimization influences vary across demographic, practice setting, and market
      characteristics. We find significant variation in influence across practice
      settings and managed care markets. Ramifications for reimbursement assessment are
      discussed.

PMID- 12182204
TI  - The application of the unified modeling language in object-oriented analysis of
      healthcare information systems.
AB  - This paper concerns itself with the beneficial effects of the Unified Modeling
      Language (UML), a nonproprietary object modeling standard, in specifying,
      visualizing, constructing, documenting, and communicating the model of a
      healthcare information system from the user's perspective. The author outlines
      the process of object-oriented analysis (OOA) using the UML and illustrates this
      with healthcare examples to demonstrate the practicality of application of the
      UML by healthcare personnel to real-world information system problems. The UML
      will accelerate advanced uses of object-orientation such as reuse technology,
      resulting in significantly higher software productivity. The UML is also
      applicable in the context of a component paradigm that promises to enhance the
      capabilities of healthcare information systems and simplify their management and
      maintenance.

PMID- 12182205
TI  - Stochastic trees and the StoTree modeling environment: models and software for
      medical decision analysis.
AB  - In this paper we present a review of stochastic trees, a convenient modeling
      approach for medical treatment decision analyses. Stochastic trees are a
      generalization of decision trees that incorporate useful features from continuous
      time Markov chains. We also discuss StoTree, a freely available software tool for
      the formulation and solution of stochastic trees, implemented in the Excel
      spreadsheet environment.

PMID- 12182206
TI  - Generating decision trees from otoneurological data with a variable grouping
      method.
AB  - When medical data sets are modelled by machine learning methods, wealth of
      variables may be available. This paper deals with variable selection for decision
      tree induction in the context of two otoneurological data sets: vertigo data, and
      postoperative nausea and vomiting data. First, a variable grouping method based
      on measures of association and graph theoretic techniques was used to gain
      insight into data. Then, representations of learning data were defined using the
      information from discovered variable groups, and decision trees were generated.
      The use of variable grouping method was beneficial by revealing interesting
      associations between variables and enabling generation of accurate and reasonable
      decision trees that modelled the application areas from different viewpoints.

PMID- 12182207
TI  - An application of linear programming discriminant analysis to classifying and
      predicting the symptomatic status of HIV/AIDS patients.
AB  - This study presents an application of linear programming discriminant analysis
      (LPDA) to classify and to predict the symptomatic status of HIV/AIDS patients. We
      applied LPDA as well as several traditional discriminant analysis methods to the
      AIDS Cost and Services Utilization Survey data set in order to demonstrate the
      use of LPDA to classify the symptomatic status of HIV/AIDS patients. The
      potential benefit of LPDA in terms of the classification accuracy was also
      analyzed.

PMID- 12182208
TI  - A method to convert HDTV videos of broadcast satellite to RealSystem multimedia
      contents.
AB  - Recently, the Internet is widely used in the field of medicine. Daily use of e
      mail for medical communication is very common. Also various information regarding
      hospitals can be accessed via the network. Apart from this practical use of the
      computer network, the mediums of telemedicine, tele-education, and telecare are
      also available. The Medical Information Network via Communications Satellite for
      University Hospital (MINCS-UH; http://www.umin.ac.jp/mincs/) was constructed by
      the Ministry of Education, Culture, Sports, Science and Technology. These
      programs feature high quality images viewed on High Definition Television (HDTV)
      through the Broadcast Satellite (BS). We have compiled a video library of MINCS
      UH program contents with W-VHS tapes for HDTV and VHS or S-VHS tapesfor NTSC,
      available to medical staff in our university hospital through the Hospital local
      area network (Hospital intranet). We have also constructed a web-based streaming
      system that is a low cost, user-friendly multimedia delivery system capable of
      providing medical lectures. This system was constructed using the RealSystem
      package with the Internet Protocol (IP) network. Although the image quality of
      RealSystem is inferior to that of the original video, users can review lectures
      and medical congress presentations with video and audio through Hospital
      intranet, at any time that is convenient to them. This system can also be an
      efficient tool for distance learning and supports the diffusion of up-to-date
      information and technology to busy physicians via the Internet.

PMID- 12182209
TI  - Decision trees: an overview and their use in medicine.
AB  - In medical decision making (classification, diagnosing, etc.) there are many
      situations where decision must be made effectively and reliably. Conceptual
      simple decision making models with the possibility of automatic learning are the
      most appropriate for performing such tasks. Decision trees are a reliable and
      effective decision making technique that provide high classification accuracy
      with a simple representation of gathered knowledge and they have been used in
      different areas of medical decision making. In the paper we present the basic
      characteristics of decision trees and the successful alternatives to the
      traditional induction approach with the emphasis on existing and possible future
      applications in medicine.

PMID- 12182210
TI  - Does size really matter--using a decision tree approach for comparison of three
      different databases from the medical field of acute appendicitis.
AB  - Decision trees have been successfully used for years in many medical decision
      making applications. Transparent representation of acquired knowledge and fast
      algorithms made decision trees one of the most often used symbolic machine
      learning approaches. This paper concentrates on the problem of separating acute
      appendicitis, which is a special problem of acute abdominal pain, from other
      diseases that cause acute abdominal pain by use of an decision tree approach.
      Early and accurate diagnosing of acute appendicitis is still a difficult and
      challenging problem in everyday clinical routine. An important factor in the
      error rate is poor discrimination between acute appendicitis and other diseases
      that cause acute abdominal pain. This error rate is still high, despite
      considerable improvements in history-taking and clinical examination, computer
      aided decision-support, and special investigation such as ultrasound. We
      investigated three databases of different size with cases of acute abdominal pain
      to complete this task as successful as possible. The results show that the size
      of the database does not necessary directly influence the success of the decision
      tree built on it. Surprisingly we got the best results from the decision trees
      built on the smallest and the biggest database, where the database with medium
      size (relative to the other two) was not so successful. Despite this we were able
      to produce decision tree classifiers that were capable of producing correct
      decisions on test data sets with accuracy up to 84%, sensitivity to acute
      appendicitis up to 90%, and specificity up to 80% on the same test set.

PMID- 12182211
TI  - Evolution in medical decision making.
AB  - The classical approach to medical decision making can be limited by the
      underlying theories. The evolutionary computation is a different concept, which
      can find many different solutions of the problem. In medicine, this is useful
      because of different expectations the decision system must face. We implemented a
      tool for genetic induction of vector decision trees, which are a good choice for
      a medical decision model because of their simplicity and transparency. The vector
      decision tree gives multiple classifications in one single pass. Evolutionary
      development of such trees achieved good results when the results were
      statistically compared to those of other classical methods. For medical
      interpretation however a cooperation with doctors is needed to verify the model
      build.

PMID- 12182212
TI  - Yohimbine administration prevents over-responsiveness to epinephrine induced by
      simulated microgravity.
AB  - BACKGROUND: Simulated microgravity produces sustained inhibition of
      sympathoneural release, turnover, and synthesis of norepinephrine (NE) and
      hypersensitization of beta-adrenergic pathways. These changes may explain the
      orthostatic intolerance experienced by astronauts returning from spaceflights.
      HYPOTHESIS: Chronic administration of yohimbine would prevent the increase of
      beta-adrenergic hypersensitivity to epinephrine (Epi) induced by simulated
      microgravity. METHODS: Eight healthy young subjects received 8 mg of yohimbine
      (an antagonist of alpha2adrenoceptors) orally twice a day during the simulated
      microgravity achieved through -6 degrees head-down bed rest (HDBR). The
      catecholamine-induced lipolysis was studied on isolated fat cells from
      subcutaneous adipose tissue before HDBR and on the fifth day of HDBR. Epi was
      infused at three graded rates (0.01, 0.02, and 0.03 microg x kg(-1) x min(-1) for
      40 min each) before and at the end of the HDBR period. The effects of Epi on the
      sympathetic nervous system (SNS) activity-assessed by plasma NE levels and
      spectral analysis of systolic BP and heart rate variability-and on plasma levels
      of glycerol, non-esterified fatty acids, glucose, and insulin and on energy
      expenditure were evaluated. RESULTS: Under yohimbine treatment, HDBR failed to
      modify urinary NE excretion and spectral variability of systolic BP in the mid
      frequency range. The beta- and alpha-adrenergic sensitivity of fat cells were not
      modified by HDBR nor were plasma NE levels and spectral variability of systolic
      BP induced by Epi infusion. No alteration of Epi-induced changes in heart rate
      and systolic and diastolic BPs were observed after HDBR. Epi-induced increases in
      plasma glucose, insulin, glycerol, and non-esterified fatty acid levels as well
      as energy expenditure were also unmodified by HDBR. Only the Epi-induced plasma
      lactate level was increased by HDBR. CONCLUSION: Our data suggest that the
      increase in the effects of Epi induced during microgravity could be attenuated by
      chronic administration of yohimbine. An explanation for this effect could be SNS
      activation brought about by the alpha2-adrenoceptor antagonist properties of
      yohimbine.

PMID- 12182213
TI  - Comparative data from 2250 male and female sports divers: diving patterns and
      decompression sickness.
AB  - BACKGROUND: The aim of the study was to compare the diving habits and histories
      of men and women in recreational scuba diving. METHODS: More than 10,000
      questionnaires were circulated to recreational divers in the United Kingdom.
      Retrospective, broad-based information was requested concerning general health,
      smoking, alcohol, recreational drug use, diving habits and histories, and
      physician-confirmed and self-diagnosed episodes of decompression sickness (DCS).
      Data relating only to women were also gathered. Questionnaires were anonymous.
      RESULTS: Over four years, 2250 divers responded, 47% of whom were women. Of the
      458,827 dives reported, 310% were by women. Differences in diving habits were
      observed between men and women, which included number of dives per annum, maximum
      depths dived, and dives with extra stops. When the level of experience was taken
      into account in this study group, the estimated rate of DCS in men was 2.60 times
      greater than for women. CONCLUSIONS: In this study, comparison between men and
      women in recreational diving differed from the initial evaluation when underlying
      factors were taken into account. Future studies should attempt to control for
      underlying factors in the data gathering and data analysis.

PMID- 12182214
TI  - Age effects on body fluid distribution during exercise in the heat.
AB  - BACKGROUND: The purpose was to study the effects of age on body fluid
      distribution during exercise and exercise combined with heat stress. METHODS: Ten
      young (Y; 23.2 +/-0.7 yr) and eight older (O; 65.3 +/- 1.0 yr) men performed two
      80-min intermittent exercise bouts on a cycle ergometer at 50% VO2peak, one in a
      thermoneutral (N), 22 degrees C environment, the other in a hot (H), 40 degrees C
      environment. For each condition, changes in serum protein, albumin, and
      electrolytes (Cl-, Na+, K+); total body water (TBW); plasma volume (PV); and
      interstitial (ISF), extracellular (ECF), and intracellular (ICF) fluids were
      determined. RESULTS: During exercise, [Cl-] responses increased more in O than Y
      (p < or = 0.05) while albumin (g) increased in Y and decreased in O (p < or =
      0.05). There were no age-related differences in total protein changes nor any of
      the other blood parameters. PV decreased similarly for all subjects in both
      conditions with larger decreases in the H environment (241.8 +/- 40.3 vs. 478.3
      +/- 46.0 mL). Loss of TBW was exacerbated in the H condition and significantly
      different (p < 0.05) between the groups (N: Y = -1.03 +/- 0.076 L, O = -0.88 +/-
      0.12 L; H: Y = -1.65 +/- 0.12 L, O = -1.85 +/- 0.14 L). The O group lost more ICF
      (p < 0.05) (N: Y = -510.4 +/- 86.8 mL, O = -631.7 +/- 115.1 mL; H: Y = -529.3 +/-
      118.0 mL, O = -928.6 +/- 118.9 mL) and less ISF (p < 0.05) (N: Y = -295.5 +/-
      101.1 mL, O = 15.8 +/- 77.6 mL; H: Y = -684.6 +/- 134.5 mL, O = -397.9 +/- 165.5
      mL) in both conditions. CONCLUSIONS: There was an interactive effect between age
      and heat stress in TBW loss. In addition, older individuals lost more ICF and
      less ISF than younger individuals during prolonged exercise. These findings
      suggest that the utilization of ICF, rather than ISF, to preserve PV during
      cycling exercise at or near 50% VO2max may be an age-related compensation.

PMID- 12182216
TI  - Speech motor control and acute mountain sickness.
AB  - BACKGROUND: An objective method that accurately quantifies the severity of Acute
      Mountain Sickness (AMS) symptoms is needed to enable more reliable evaluation of
      altitude acclimatization and testing of potentially beneficial interventions.
      HYPOTHESIS: Changes in human articulation, as quantified by timed variations in
      acoustic waveforms of specific spoken words (voice onset time; VOT), are
      correlated with the severity of AMS. METHODS: Fifteen volunteers were exposed to
      a simulated altitude of 4300 m (446 mm Hg) in a hypobaric chamber for 48 h.
      Speech motor control was determined from digitally recorded and analyzed timing
      patterns of 30 different monosyllabic words characterized as voiced and unvoiced,
      and as labial, alveolar, or velar. The Environmental Symptoms Questionnaire (ESQ)
      was used to assess AMS. RESULTS: Significant AMS symptoms occurred after 4 h,
      peaked at 16 h, and returned toward baseline after 48 h. Labial VOTs were shorter
      after 4 and 39 h of exposure; velar VOTs were altered only after 4 h; and there
      were no changes in alveolar VOTs. The duration of vowel sounds was increased
      after 4 h of exposure and returned to normal thereafter. Only 1 of 15 subjects
      did not increase vowel time after 4 h of exposure. The 39-h labial (p = 0.009)
      and velar (p = 0.037) voiced-unvoiced timed separations consonants and the
      symptoms of AMS were significantly correlated. CONCLUSIONS: Two objective
      measures of speech production were affected by exposure to 4300 m altitude and
      correlated with AMS severity. Alterations in speech production may represent an
      objective measure of AMS and central vulnerability to hypoxia.

PMID- 12182215
TI  - Energy intake deficit and physical performance at altitude.
AB  - BACKGROUND: Physical performance of sea-level (SL) residents acutely exposed to
      altitude (ALT) is diminished and may improve somewhat with ALT acclimatization.
      HYPOTHESIS: A large reduction in lean body mass (LBM), due to severe energy
      intake deficit during the first 21 d of ALT (4300 m) acclimatization, will
      adversely affect performance. METHODS: At ALT, 10 men received a deficit (DEF) of
      1500 kcal x d(-1) below body weight (BW) maintenance requirements and 7 men
      received adequate (ADQ) kcal x d(-1) to maintain BW. Performance was assessed by:
      1) maximal oxygen uptake (VO2max); 2) time to complete 50 cycles of a lift and
      carry task (L+C); 3) number of one-arm elbow flexions (10% BW at 22 flexions x
      min(-1); and 4) adductor pollicis (AP) muscle strength and endurance time
      (repeated 5-s static contractions at 50% of maximal force followed by 5-s rest,
      to exhaustion). Performance and body composition (using BW and circumference
      measures) were determined at SL and at ALT on days 2 through 21. RESULTS: At SL,
      there were no between-group differences (p > 0.05) for any of the performance
      measures. From SL to day 21 at ALT, BW and LBM declined by 6.6 +/- 3 kg and 4.6
      kg, respectively, for the DEF group (both p < 0.01), but did not change (both p >
      0.05) for the ADQ group. Performance changes from day 2 or 3 to day 20 or 21 at
      ALT were as follows (values are means +/- SD): VO2max (ml x min(-1)): DEF = +97
      +/- 237, ADQ = +159 +/- 156; L + C (s): DEF = -62 +/- 35*, ADQ = -35 +/- 20* (*p
      < 0.05; improved from day 3); arm flex (reps): DEF = -2 +/- 7, ADQ = +2 +/- 8; AP
      endurance (min): DEF = +1.4 +/- 2, ADQ = + 1.9 +/- 2; AP strength (kg): DEF = 
      0.7 +/- 4, ADQ = -1.2 +/- 2. There were no differences in performance between
      groups. CONCLUSIONS: A significant BW and LBM loss due to underfeeding during the
      first 21 d of ALT acclimatization does not impair physical performance at ALT.

PMID- 12182218
TI  - Head and eye movements in visual search using night vision goggles.
AB  - BACKGROUND: Night-vision goggles (NVGs) provide only a restricted field of view
      and have other characteristics that may affect the head and eye movements used in
      visual search. METHODS: We measured head scan patterns, the magnitude and
      duration of gaze saccades, and fixation duration as subjects searched computer
      generated imagery either with or without NVGs. Subjects searched for either a
      large (6 degrees) target on a low-detail background (high conspicuity condition)
      or a small (2 degrees) target on a high-detail background (low conspicuity
      condition). RESULTS: All subjects displayed head-scan patterns that were
      qualitatively similar to those reported in the literature. Although both head
      scan speed and amplitude were higher for the NVG condition as compared with the
      no-NVG condition, the difference was not statistically significant. Head-scan
      speed did vary significantly with target conspicuity, however. Gaze saccade
      amplitude varied with target conspicuity but only when NVGs were used. Fixation
      duration did not vary with either NVG use or target conspicuity. A two-parameter
      (exponent and scaling parameter) power function was fitted to the amplitude
      duration data. The power-function exponents varied from about 0.30 to 0.44, but
      there was a concommitant variation in the scaling parameter, and the result was
      no significant difference in the form of the power functions fitted to the data.
      CONCLUSIONS: NVG use did not significantly affect any of the individual head or
      eye movement variables involved in searching the computer-generated imagery
      studied here. However, the decrease in gaze-saccade amplitude with increased
      target conspicuity when NVGs were used is evidence of the sensitivity of the head
      and eye movement measurement techniques used here, and suggests that all
      available measures of response efficiency be considered when evaluating NVGs
      using complex stimuli.

PMID- 12182217
TI  - The effect of simulated weightlessness on hypobaric decompression sickness.
AB  - BACKGROUND: A discrepancy exists between the incidence of ground-based
      decompression sickness (DCS) during simulated extravehicular activity (EVA) at
      hypobaric space suit pressure (20-40%) and crewmember reports during actual EVA
      (zero reports). This could be due to the effect of gravity during ground-based
      DCS studies. HYPOTHESIS: At EVA suit pressures of 29.6 kPa (4.3 psia), there is
      no difference in the incidence of hypobaric DCS between a control group and group
      exposed to simulated weightlessness (supine body position). METHODS: Male
      subjects were exposed to a hypobaric pressure of 29.6 kPa (4.3 psi) for up to 4
      h. The control group (n = 26) pre-oxygenated for 60 min (first 10 min exercising)
      before hypobaric exposure and walking around in the altitude chamber. The test
      group (n = 39) remained supine for a 3 h prior to and during the 60-min pre
      oxygenation (also including exercise) and at hypobaric pressure. DCS symptoms and
      venous gas emboli (VGE) at hypobaric pressure were registered. RESULTS: DCS
      occurred in 42% in the control and in 44% in simulated weightlessness group
      (n.s.). The mean time for DCS to develop was 112 min (SD +/- 61) and 123 min (+/-
      67), respectively. VGE occurred in 81% of the control group subjects and in 51%
      of the simulated weightlessness subjects (p = 0.02), while severe VGE occurred in
      58% and 33%, respectively (p = 0.08). VGE started after 113 min (+/- 43) in the
      control and after 76 min (+/- 64) in the simulated weightlessness group.
      CONCLUSIONS: No difference in incidence of DCS was shown between control and
      simulated weightlessness conditions. VGE occurred more frequently during the
      control condition with bubble-releasing arm and leg movements.

PMID- 12182219
TI  - Corneal injury threshold in rabbits for the 1540 nm infrared laser.
AB  - BACKGROUND: In the 40 yr since lasers were invented, they have become commonplace
      in military operations, and while their utility in this setting is undeniable,
      they also represent a potential hazard for those in contact with them. This
      threat must be recognized, information must be gathered to understand this injury
      potential, and the necessary measures must be taken to properly protect those who
      will work, train, and fight with these systems. The exact mechanisms of
      laser/tissue interaction at 1540 nm are not well understood. Previous studies and
      textbooks show remarkable disparity in reporting where 1540 nm laser energy is
      deposited and the quantity of energy required to cause tissue damage. Rabbit
      cornea is very similar histologically to that of humans with the exception that
      it lacks Bowman's membrane. This model has been recommended as a reasonable
      approximation by past researchers and avoids the use of valuable non-human,
      primate research animals. METHODS: A rabbit model was used to demonstrate the
      ability of the 1540 nm laser to produce corneal injuries. Various energies were
      applied to find the threshold at which injury is consistently produced.
      Observations included the appearance of the injury in the rabbit cornea. All
      rabbits were between 5 and 6 kg. RESULTS: Corneal injury was consistent at
      energies above 56 J x cm(-2). Injuries involved the deeper corneal stroma rather
      than only the epithelial layer, thus raising concern for permanent visual
      disability in those affected. The gross appearance of these injuries was white
      opaque areas easily seen within the corneal stroma. CONCLUSIONS: Data shows
      conclusively that the 1540 nm laser causes significant corneal damage at
      reproducible energy levels. Further research is clearly necessary to advance our
      understanding of the role of Bowman's membrane, the healing properties of the
      injured cornea, and the epidemiology of laser injury.

PMID- 12182220
TI  - Aeromedical waiver status in U.S. Naval aviators involved in Class A mishaps.
AB  - PURPOSE: U.S. Naval aviators are subject to stringent aeromedical standards.
      Aeromedic waivers are considered when a naval aviator develops a medical
      condition that is deemed safe for flight, allowing that aviator to continue in a
      flying status. No Class A (serious) mishap to date has been directly attributable
      to an aviator's waivered condition. However, to date no study has been conducted
      to review the overall mishap rate among aviators who are flying with a waiver.
      This study evaluated the aeromedical waiver status of naval aviators involved in
      Class A mishaps from 1992-1999. METHOD: Aviation mishaps in the U.S. Navy are
      investigated by trained personnel, who report their detailed findings to the U.S.
      Naval Safety Center (NSC). The Navy Operational Medicine Institute (NOMI)
      maintains a database of all aviation physicals, including the waiver status of
      individual aviators. A collaborative NSC/NOMI study was done to investigate the
      prevalence of waivers in mishap and non-mishap aviators. Records were retrieved
      on 234 naval aviators who were the "pilot at the controls" of Class A mishaps
      occurring from 1992-1999. This mishap waiver rate was compared with the baseline
      waiver rate for all pilots in 1994 (midpoint). Odds Ratios were calculated of
      having a Class A mishap if the aviator had a waiver. RESULTS AND CONCLUSIONS:
      Analysis failed to find a statistical difference in waiver rates between mishap
      aviators and the general naval aviator population indicating that the U.S. Naval
      Aeromedical Service is providing aeromedically safe naval aviators to the fleet.

PMID- 12182221
TI  - Epidemic decompression sickness: case report, literature review, and clinical
      commentary.
AB  - BACKGROUND: Decompression sickness (DCS) is a syndrome of symptoms caused by
      bubbles of inert gas. These bubbles are produced by a significant ambient
      pressure drop. Although cases are usually solitary there have been several
      episodes of DCS clusters. This paper reports an episode of epidemic decompression
      sickness and reviews the literature. METHODS: The case reported describes six
      aircrewmen with DCS following an unpressurized AC-130 flight (maximum altitude
      17,000 ft). Two obvious concerns-the low altitude at which DCS was encountered
      and the potential for epidemic hysteria-are discussed and discounted. In
      addition, factors contributing to this case are recounted in depth. Moreover, the
      literature was examined for similar cases of epidemic decompression sickness.
      Four other instances were discovered. Detailed qualitative analysis of these five
      reports was performed. RESULTS: With this information epidemic decompression
      sickness is defined and classified. Two types are described-individual-based (Epi
      I) and population-based (Epi-P). Epi-I is a cluster of DCS following a solitary
      exposure; whereas, Epi-P is a cluster of DCS following multiple exposures over
      time. Investigation of Epi-P follows the classical rules of outbreak
      investigation (time, place, person, and environment); whereas, Epi-I does not. In
      fact, the focus in Epi-I is almost entirely the environment. Following this
      outline should produce an etiology that control measures can be directed against.
      However, it is prudent to look beyond the etiology. Enter the Haddon Matrix, a
      classic public health tool that considers counter-measures before, during, and
      after the event. CONCLUSION: These many concepts are illustrated with the
      presented case. Following this template, both the expert and the novice flight
      surgeon have a systematic and reproducible approach to these difficult puzzles.

PMID- 12182222
TI  - Task and postural factors are related to back pain in helicopter pilots.
AB  - BACKGROUND: A previous survey by Shear et al. revealed a high prevalence of back
      pain in Royal Navy helicopter aircrew, compared with controls. It was recommended
      that a second survey be undertaken, taking account of flying tasks and cockpit
      ergonomics. This was the purpose of the present investigation. METHOD: A
      questionnaire containing items on back pain and posture was circulated to all 246
      acting pilots, with returns of 75%. The questionnaire sought information on pain
      in both the flying pilot and co-pilot/instructor roles. RESULTS: The 12-mo
      prevalence of back pain was 80%. Task-related back pain was greatest in
      instrument flying (72%) and least in the co-pilot and instructor roles (24%).
      Self-ratings of posture indicated that forward flexed trunk postures predominated
      in the flying roles and were most extreme in instrument flying. In non-flying
      roles, symmetrical, reclining postures were more often reported. No demographic
      or psychosocial variables were significantly related to back pain prevalence or
      disability. CONCLUSIONS: Much of the back pain experienced by helicopter pilots
      appears to be due to the posture needed to operate the cyclic and collective
      controls. In instrument flying, it is suggested that the visual demands of
      scanning the displays may exacerbate the pain by causing the pilot to lean
      further forward.

PMID- 12182223
TI  - Prevention of carbon monoxide exposure in general and recreational aviation.
AB  - Carbon monoxide exposure is an important public health issue that poses a
      significant, albeit uncommon risk in aviation. Exposure is most common in single
      engine piston-driven aircraft where air is passed over the exhaust manifold to
      serve as cabin heat. Effective primary prevention of this exposure is the regular
      inspection and maintenance of aircraft exhaust systems, as required by law. For
      situations at special risk should exposure occur, and where there is concern for
      the public safety, installation of active warning devices for CO intrusion into
      cockpits may improve secondary prevention. Modern studies should be performed of
      occupation-specific abilities to support the 50 ppm FAA CO exposure standard and
      50-70 ppm FAA Technical Standard Order (TSO) for CO monitors alerting pilots to
      the possibility of exhaust gas intrusion into their cockpits.

PMID- 12182225
TI  - "Vibroacoustic disease".

PMID- 12182224
TI  - Human factors analysis of accidents involving visual flight rules flight into
      adverse weather.
AB  - BACKGROUND: General aviation (GA) accident statistics indicate that visual flight
      rules (VFR) flight into instrument meteorological conditions (IMC) is a major
      safety hazard. However, little research has been conducted to identify the
      factors that influence VFR pilots' decisions to risk flying into deteriorating
      weather. The purpose of the present study was to further examine the causes of GA
      accidents associated with VFR flight into IMC. METHOD: A comprehensive review of
      GA accident reports maintained by the National Transportation Safety Board (NTSB)
      was conducted to identify accidents involving VFR flight into IMC between January
      1990 and December 1997. These accidents were compared with other GA accidents
      that occurred during the same time period. RESULTS: Analyses of these accidents
      revealed that VFR flight into IMC accidents were more likely to involve less
      experienced pilots and to have passengers aboard the accident aircraft compared
      with the other GA accidents. In addition, most VFR flight into IMC accidents were
      considered by the NTSB to have involved intentional flight into adverse weather
      by the pilot. DISCUSSION: These findings are interpreted in terms of their
      implications for the underlying causes of VFR flight into IMC, including
      situation assessment, risk perception, and social pressure. Intervention programs
      that address all of these factors are needed.

PMID- 12182226
TI  - The secreted aspartic proteinases as a new target in the therapy of candidiasis.
AB  - Secreted aspartic proteinases (Saps) are important virulence factors in different
      types of candidiasis caused by Candida albicans (C. albicans). The various
      isoenzymes are expected to fulfil different tasks during mucosal or disseminated
      infections. It could be shown that the introduction of the proteinase inhibitors
      like saquinavir and indinavir in the therapy of human immunodeficiency virus
      (HIV) infected patients has an effect on Sap activity in vitro as well as in
      vivo. Therefore, drugs like the HIV proteinase inhibitors could play an essential
      role in the treatment of candidiasis in the future, especially if further adapted
      to this target.

PMID- 12182228
TI  - Therapeutic strategies for hepatitis B virus-associated hepatocellular carcinoma.
AB  - Hepatocellular carcinoma (HCC) is a one of the most prevalent cancers worldwide,
      especially in the Asia Pacific region. At present, the five-year survival of
      individuals with HCC is low, mainly due to the late presentation of the disease,
      and limited therapeutic options. The major risk factors for HCC in the Asia
      Pacific region include hepatitis B and C viral infection. Removing or reducing
      these risk factors, such as by immunizing against the hepatitis B virus, may
      reduce the incidence of hepatitis B-associated HCC in the distant future.
      However, immunization does not decrease the risk of HCC in individuals who are
      currently infected with HBV worldwide highlighting the continued importance of
      examining strategies for the treatment of HCC. Current treatment strategies
      include surgical resection, liver transplantation, chemotherapy, transcatheter
      arterial chemoembolism and percutaneous injection. Except for surgical resection
      and liver transplantation, which represent the most viable treatment options,
      most of the other present treatments are mainly for palliation. Hence novel
      treatment modalities continue to be investigated and several of these are
      currently in clinical trials. One of the more promising novel approaches for HCC
      treatment is gene therapy. Potential promising gene therapeutic approaches for
      the treatment of HCC include augmentation of tumor suppressor genes, inhibition
      of abnormally over-expressed oncogenes as well as specifically inducing death of
      cancer cells either via "suicide" gene therapy, conditional replicative
      adenovirus strategy, immunomodulation or inhibiting tumor angiogenesis.
      Nonetheless, successful implementation of these gene therapeutic approaches is
      dependent on overcoming current practical and technical hurdles underscoring the
      need for a better understanding of the basic aspects of gene therapy.

PMID- 12182227
TI  - ETS proteins and MMPs: partners in invasion and metastasis.
AB  - Binding sites for the ETS domain family of transcription factors are found in the
      promoters of the matrix metalloproteinase (MMP) family of matrix degrading
      enzymes. Evidence is accumulating that both these groups of molecules are
      important in the process of angiogenesis in addition to matrix degradation.
      Furthermore, they are both expressed in tumor tissue as well as in the normal
      surrounding stroma. These factors along with various sites at which they may be
      regulated collectively makes them attractive targets to consider for therapeutic
      intervention in the processes of invasion and metastasis.

PMID- 12182229
TI  - HMG-Co A reductase inhibitors in the treatment of cardiovascular diseases:
      stabilization of coronary artery plaque.
AB  - 3-Hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors (statins)
      are greatly contributed to the treatment of hypercholesterolemia, and constitute
      an important part of comprehensive strategies for the treatment of cardiovascular
      disease in the 21st century. Particularly, a strategy for preventing acute
      coronary syndrome (ACS), the most important complication of hyperlipidemia, is
      urgently needed. Recent research has revealed a new mechanism of prevention of
      coronary heart disease by statins: they not only lowered cholesterol level as
      previously reported, but also contribute directly to plaque stabilization. Among
      many statins recently marketed, some act directly onto the blood vessel wall to
      stabilize plaques already formed (so-called vascular statins), while statins are
      originally classified as chemical or non-chemical. At the same time, reports on
      pleiotropic activities of statins, including improvement of osteoporosis, have
      accumulated to suggest an extended role of statins, not merely as a hypolipidemic
      agent but also possibly an anti-arteriosclerotic/anti-aging drug. This article
      reviews the direct action of statins on the blood vessel wall, with reference to
      classification of statins based on difference in action on the blood vessel wall
      (hepatic statins vs. vascular statins).

PMID- 12182230
TI  - Computational function assignment for potential drug targets: from single genes
      to cellular systems.
AB  - Biomedical science is currently undergoing an epoch-marking transition from its
      classical phase to the post-genome era. The outstanding success of world-wide
      genome sequencing efforts, evidenced by the recent publication of the draft of
      the human genome, together with the completion of several genomes of eukaryotic
      model organisms and the availability of microbial genome sequences, is opening up
      data sources of unprecedented scale for drug discovery. Furthermore, the
      elucidation of genome expression states through transcriptomic and proteomic
      techniques is playing a crucial role in the characterisation of disease at the
      molecular level. At the same time, our still very limited knowledge of the
      biological functions of genes and proteins at different levels of cellular
      organisation is preventing full exploitation of the available data. This review
      will discuss current computational techniques for function prediction based on
      the sequence-structure-function paradigm. Newly emerging approaches aimed at
      gaining an expanded understanding of function through integration of data from
      various sources and modelling of complex cellular systems will also be
      highlighted.

PMID- 12182231
TI  - Tumor cell-based vaccination in renal cell carcinoma: rationale. approaches, and
      recent clinical development.
AB  - Since there is some evidence for spontaneous immunity against renal cell
      carcinoma, vaccination strategies are often used in patients with this tumor
      type, both in the adjuvant and the metastatic setting. Therefore, therapeutic
      strategies aim at augmenting anti-tumor immunity, but tumor-specific antigens
      suitable for vaccination purposes in renal cell carcinoma still remain to be
      identified. Early approaches used whole tumor cells or cell lysates with or
      without non-specific adjuvants like BCG. Studies investigating tumor cell
      vaccines have demonstrated immunological responses following vaccination, like
      positive cutaneous delayed hypersensitivity reactions indicating biological
      acitivity of tumor cell vaccines, and clinical responses have been observed as
      well. However, no clinical benefit has been demonstrated in randomized phase III
      trials. In recent years, efforts to develop more potent vaccines resulted in more
      sophisticated methods of tumor vaccination: The insertion of "neo-antigens" to
      enhance immunogenicity, the insertion of T-cell co-stimulatory molecules to
      enhance anti-tumor T-cell activation and the local production of cytokines to
      enhance T-cell function or the migration of antigen-presenting cells. Tumor cells
      have been genetically modified to express and produce cytokines, which in turn
      enhance the immunogenicity of the vaccine. The important role of dendritic cells
      has been recognized and tumor antigen-pulsed dendritic cells have been proposed.
      Hybrid cell vaccines are another promising approach. Safety and some
      effectiveness of these vaccines were demonstrated in phase I and II trials.
      However, randomized phase III trials are mandatory to confirm the usefulness of
      vaccination strategies. This review will describe the principals of tumor
      vaccination and, in a second part, focus on clinical studies of tumor vaccination
      in patients with renal cell carcinoma.

PMID- 12182232
TI  - Evaluation by SDS-Page and immunoblotting of residual antigenicity in gluten
      treated wine: a preliminary study.
AB  - Hydrolyzed gluten could be a suitable alternative to animal proteins in the wine
      clarification process, but the residual proteins could constitute a risk for
      subjects suffering from celiac disease or allergy to cereals. The aim of this
      study was to investigate possible traces of gluten in treated wine and to assess
      its antigenicity in commercial products. The presence of gluten in treated wine
      was evaluated by an electrophoretic method [sodium dodecylsulfate-polyacrylamide
      gel electrophoresis (SDS-PAGE)] and its immunoreactivity was evaluated by
      immunoblotting. No traces of protein were found in untreated samples. A small
      quantity of protein was detected in treated wine but this produced no significant
      immunochemical reaction. In an experimental clarification process, a protein
      fraction was detectable in untreated samples and in the first stages of the
      clarification process. However, there was no significant gluten-associated
      immunochemical reaction in clarified wine samples, confirming strong binding
      between the clarifying agent and the phenolic fraction. In conclusion, the
      clarifying process strongly reduced the amount of protein material, at least in
      red wines. Under the most restrictive tests of the presence of gluten in the
      product, the predictable residue of gluten in wine was safe for celiac subjects.
      For allergic subjects the data are less conclusive because there is no known
      limit for allergic reactions, but clear labeling of the method of treating the
      wine should also protect this group of consumers.

PMID- 12182233
TI  - Inhibitory activity of the white wine compounds, tyrosol and caffeic acid, on
      lipopolysaccharide-induced tumor necrosis factor-alpha release in human
      peripheral blood mononuclear cells.
AB  - The objective of this study was to assess whether tyrosol and caffeic acid are
      able to inhibit lipopolysaccharide (LPS)-induced tumor necrosis factor (TNF)
      alpha release. TNF is one of the most important cytokines involved in
      inflammatory reactions. The results show that both tyrosol and caffeic acid are
      able to inhibit LPS-induced TNF-alpha release from human monocytes, even at low
      doses. Their mechanisms of action are discussed and we conclude that high doses
      of the two compounds are not required to achieve effective inhibition of
      inflammatory reactions due to TNF-alpha release.

PMID- 12182234
TI  - Both serum receptors of tumor necrosis factor are influenced by mud pack
      treatment in osteoarthrotic patients.
AB  - Several authors have demonstrated the pivotal role of proinflammatory cytokines
      in inducing progressive cartilage degradation and secondary inflammation of the
      synovial membrane in osteoarthritis (OA). It has recently been established that
      tumor necrosis factor (TNF)-alpha plays a well-defined role in the
      pathophysiology of inflammatory joint diseases and that binding to circulating
      soluble TNF-alpha receptors can inactivate it. We investigated the influence of
      mud pack treatment, which is able to diminish TNF-alpha serum values, on specific
      TNF receptor (sTNF-R) levels. Thirty-six patients with OA were enrolled and
      randomized into two groups. Group A underwent mud pack treatment and group B
      underwent thermal bath treatment. A group of 20 healthy untreated subjects was
      used as a control. Blood samples were collected at baseline and after treatment,
      and assays of sTNF-R55 and sTNF-R75 were performed in both groups. We found small
      changes in sTNF-Rs serum values but these were not statistically significant.
      sTNF-R55 serum values decreased by 0.4% after the therapy in group A, while in
      group B the decrease was -17.7%. sTNF-R75 was reduced by -21.17% in group A and
      by -10.6% in group B. In conclusion, through its thermic and ant/inflammatory
      activity mud pack treatment shows complex interaction with the most common
      factors of inflammatory and cartilage degradation. Our results suggest that the
      thermic component of this natural treatment is mainly involved in modulating
      inflammatory reaction and cartilage damage through binding of the circulating
      TNF, which controls the activation of the cells responsible for the production of
      proinflammatory cytokines.

PMID- 12182235
TI  - Low molecular weight hyaluronic acid prevents oxygen free radical damage to
      granulation tissue during wound healing.
AB  - Hyaluronic acid protects granulation tissue from oxygen free radical damage and
      stimulates wound healing, but its molecular weight prevents it from permeating
      the epidermal barrier A low molecular weight hyaluronic acid preparation is able
      to permeate the skin, but it is unknown whether or not it retains the scavenging
      effects of oxygen free radicals in granulation tissue. Our experiments were
      conducted in rats with excisional or incisional wounds. Wound contraction over 11
      days and breaking strength on the fifth day were measured. Oxygen free radical
      production was induced by intraperitoneal administration of two different
      xenobiotics: phenazine methosulfate and zymosan. The wounds were treated
      topically with low molecular weight hyaluronic acid (0.2%) cream or placebo. In
      the incisional wound group, the effects of superoxide dismutase were also
      determined. Absolute controls received wounds and placebo but no xenobiotics.
      Wound healing was significantly slower in the xenobiotic group than in the
      control groups. These effects were strongly reduced by topical administration of
      low molecular weight hyaluronic acid (0.2%) cream and in incisional wounds by
      topically injected superoxide dismutase. Low molecular weight hyaluronic acid is
      effective as the native compound against oxygen free radicals. Its
      pharmacological effects through transdermal administration should be tested in
      appropriate models.

PMID- 12182236
TI  - Hyperprolactinemia does not influence hypothalamic-pituitary-adrenocortical
      function during hypoglycemia in women.
AB  - Elevated plasma prolactin and mild hypocortisolemia have been observed in
      patients with rheumatic disorders. This study was designed to assess the
      potential inhibitory effect of hyperprolactinemia on hypothalamic-pituitary
      adrenocortical function. Hypoglycemia was induced by intravenous insulin
      injection (0.1 IU/kg) in 10 female volunteers of fertile age during their
      follicular phase twice: 60 min after either domperidone (10 mg orally) or placebo
      administration. Blood samples were collected from an indwelling catheter inserted
      into the cubital vein at -60, 0, 30, 45, 60 and 90 min. The concentrations of
      prolactin, adrenocorticotropic hormone (ACTH), cortisol, epinephrine,
      norepinephrine and glucose were measured in plasma. Domperidone administration
      significantly increased plasma prolactin concentrations (71 +/- 11 ng/ml vs. 14
      +/- 6 ng/ml; p <0.001), while basal plasma concentrations of ACTH, cortisol,
      norepinephrine and epinephrine were unaffected. Insulin-induced hypoglycemia
      resulted in a significant rise in the mean plasma ACTH levels from 10 +/- 1 pg/ml
      (domperidone) and 11 +/- 1 pg/ml (controls) to 148 +/- 19 pg/ml (domperidone) and
      139 +/- 12 pg/ml (controls) at 45 min (p < 0.001), in plasma cortisol from 407 +/
      62 nmol/l (domperidone) and 391 +/- 42 nmol/l (controls) to 925 +/- 60 nmol/l
      (domperidone) and 810 +/- 52 nmol/l (controls) at 60 min (p < 0.001), and in
      plasma epinephrine from 40 +/- 26 pg/ml (domperidone) and 16 +/- 3 pg/ml
      (controls) to 274 +/- 55 pg/ml (domperidone) and 352 +/- 61 pg/ml (controls) at
      30 min; (p < 0.001). The significant increase in ACTH, cortisol and epinephrine
      responses to hypoglycemia was similar in both groups. We observed mild
      norepinephrine response to hypoglycemia but this was irrespective of the
      medication. In conclusion, pharmacologically-induced hyperprolactinemia did not
      induce significant changes of hypothalamic-pituitary-adrenocortical function and
      did not influence sympathoadrenal activity in healthy young women.

PMID- 12182237
TI  - Assessment of technical surgical skills.
AB  - OBJECTIVE: To review methods of assessment of technical surgical competence, and
      to point out the potential benefit of such assessment to training and safe
      practice. DESIGN: Review of publications about methods of evaluation of technical
      surgical competence. Studies were identified through MEDLINE using the keywords
      surgery, assessment, operative skills, training, and competence. The references
      cited in these studies were reviewed to find out whether any other trials fitted
      the selection criteria. SETTING: Teaching hospital, Denmark. RESULTS: There are
      several validated methods that allow objective assessment of operative skills for
      both open and laparoscopic surgery. CONCLUSIONS: Objective assessment of
      technical surgical skills is possible and reliable and valid methods are
      available. There are good reasons to implement evaluation programmes as a part of
      surgical education.

PMID- 12182238
TI  - Applied anatomy of the genital branch of the genitofemoral nerve in open inguinal
      herniorrhaphy.
AB  - OBJECTIVE: To record the anatomical variations and clinical importance of the
      genital branch of the genitofemoral nerve in the inguinal canal. DESIGN:
      Neuropathology study. SETTING: General hospital, Taiwan. SUBJECTS: 58 cadavers.
      INTERVENTIONS: 116 dissections findings of the genitofemoral nerve in the
      inguinal canal. MAIN OUTCOME MEASURES: Anatomical variations. RESULTS: All the
      genital branches passed through the ventral aspect of the internal ring. Almost
      all these branches entered the ring and continued within the spermatic cord
      between the fibres of the cremaster and the internal spermatic fascia. In 59% the
      nerve was related to the inferior fibres and in 38% it was in relation to the
      lateral or medial fibres. In only 3% did the genital branch run outside the
      spermatic cord. CONCLUSION: To avoid damage to the genital branch of the
      genitofemoral nerve, suturing should be done over the dorsal aspect of the
      internal ring. The cremaster should be incised longitudinal rather than
      transversely and the genital branch of the genitofemoral nerve should be
      identified before repair of the posterior wall.

PMID- 12182239
TI  - Outcome of repair of bilateral groin hernias: a prospective evaluation of 1,487
      patients.
AB  - OBJECTIVE: To find out whether simultaneous repair of bilateral hernias increases
      the risk of recurrence compared with unilateral repair. DESIGN: Prospective
      study. SETTING: Swedish hospitals participating in the Swedish Hernia Register
      (SHR). INTERVENTIONS: Prospective collection of data from the SHR, 1992-1999
      inclusive. The Cox proportional hazard test was used for calculating odds ratio
      (OR). MAIN OUTCOME MEASURES: Hernia repairs were followed up in a life table
      fashion until re-operation for recurrence or death of the patient. RESULTS: 33416
      unilateral and 1487 bilateral operations on 2974 groin hernias were found. Direct
      hernias were more common in the bilateral than in the unilateral group, 1,825,
      61% compared with 13,336, 40%, (p < 0.0001). A laparoscopic method was used for
      1774 (60%) of bilateral and 3285 (10%) unilateral repairs, and 455 bilateral
      operations (31%) were done as day cases compared with 18376 (55%) unilateral ones
      (p < 0.0001 for both comparisons). The cumulative incidence of reoperation at
      three years for groin hernias after bilateral and unilateral repair was 4.1% (95%
      confidence interval 3.1% to 5.1%) and 3.4% (95% Cl 3.1% to 3.7%, respectively.
      After adjustment for other risk factors, the OR for reoperation for recurrence
      after bilateral repair was 1.2 (95% CI 0.9 to 1.5) with unilateral repair as
      reference. The OR for reoperation after laparoscopic bilateral repair compared
      with open bilateral repair was 0.9 (95% CI 0.6 to 1.4). CONCLUSIONS: Simultaneous
      repair of bilateral hernias does not increase the risk of reoperation for
      recurrence and there is no significant difference in the risk of reoperation
      after bilateral repair using open or laparoscopic techniques.

PMID- 12182240
TI  - Preoperative management is more important than choice of sutured or stapled
      anastomosis in Crohn's disease.
AB  - OBJECTIVE: To find out if there were any differences in postoperative
      complications and anastomotic leak rate between sutured and stapled anastomoses
      after bowel resection in patients exposed to the same preoperative management
      programme. DESIGN: Prospective observational non-randomised study. SETTING:
      Colorectal unit, Sweden. PATIENTS: Between 1996 and 2000 bowel resections with
      anastomosis were done for 42 consecutive patients with Crohn's disease. 20
      patients had their anastomoses sutured (sutured group) and 22 had their
      anastomosis stapled (stapled group) over two successive periods. MAIN OUTCOME
      MEASURES: Postoperative complications and anastomotic leak rate. RESULTS: None of
      the patients were on immunosuppressive treatment and about half in each group had
      had several weeks of preoperative enteral nutrition. No anastomotic-related
      complications and few other postoperative complications were noted, irrespective
      of the anastomotic technique used. CONCLUSION: A strategy to operate on Crohn
      patients without steroids and, if indicated, treated preoperatively with enteral
      nutrition and percutaneous drainage of abscesses resulted in no anastomotic leaks
      and few postoperative complications. These results were independent of the
      anastomotic technique used.

PMID- 12182241
TI  - New approaches in the management of rectal carcinoma result in reduced local
      recurrence rate and improved survival.
AB  - OBJECTIVE: To find out whether total mesorectal excision (TME) technique alone or
      combined with preoperative radiotherapy reduces local recurrence rate and
      improves survival. DESIGN: Partly retrospective (the first period), partly
      prospective (the second period) study. SETTING: University hospital, Helsinki,
      Finland. SUBJECTS: 144 patients between 1980 and 1990 and 61 patients between
      1991 and 1997 with rectal cancer, who underwent major curative surgery.
      INTERVENTIONS: A conventional surgical technique was used during the first period
      and TME alone or combined with preoperative radiotherapy when appropriate during
      the second period. MAIN OUTCOME MEASURES: Postoperative morbidity and mortality,
      local recurrence rate, and 5-year survival. RESULTS: After anterior resection
      4/76 of the patients (5%) during the first period and 8/43 (19%) during the
      second period developed anastomotic leaks. Operative 30-day mortality was 1% (n =
      1) and 0, respectively. Actuarial local recurrence rate was 17% in the first
      period and 9% in the second period. Actuarial crude 5-year survival improved from
      55% to 78% and cancer-specific survival from 67% to 86% between the two study
      periods. CONCLUSIONS: Despite an increased number of anastomotic complications
      TME is safe. Refinement of the surgical technique together with preoperative
      radiotherapy yields lower local recurrence rates and an improved survival
      compared with conventional surgery alone.

PMID- 12182242
TI  - An intraluminal prosthesis may improve healing of a one-layer colonic
      anastomosis: an experimental study in pigs.
AB  - OBJECTIVE: To compare healing of one-layer colonic anastomoses with or without a
      soluble intraluminal prosthesis (* SBS-tube). DESIGN: Randomised, partly blinded
      controlled study. SETTING: University hospital, Denmark. SUBJECTS: 16 female
      Danish country strain pigs, of which 8 had the SBS tube inserted and 8 acted as
      controls. INTERVENTIONS: One-layer colonic anastomoses either hand-sewn (n = 8,
      controls) or hand-sewn onto an SBS tube (n = 8). MAIN OUTCOME MEASURES:
      Macroscopic evaluation, leakage test, breaking strength, histology, oxygen
      tension in and near the anastomosis peroperatively and 4 days postoperatively.
      RESULTS: Three quarters of the tubes (n = 8) dissolved in less than 2 hours.
      Histological examination showed significantly better structured layers and more
      mucosal epithelial covering in the SBS group. The other histological variables
      examined were: tissue gap (p < 0.08), inflammation (p < 0.10), breaking strength
      (p < 0.46) and amount of granulation tissue (p < 0.71), but the last findings
      were not significant. Oxygen tension at the anastomotic line was better in the
      SBS tube group, but not significantly so. CONCLUSIONS: We conclude that the SBS
      tube facilitates the sewing of the anastomosis and may improve healing, possibly
      because of better apposition of the cut ends and reduced tension in the sutures.

PMID- 12182243
TI  - Training for advanced laparoscopic surgery.
AB  - OBJECTIVE: To evaluate the efficiency of training for advanced minimally-invasive
      surgery in rats. SETTING: Teaching hospital, Germany. SUBJECTS: 10 surgical
      residents with few laparoscopic training skills had two days laparoscopic
      microsurgical training using rats. INTERVENTIONS: Increasingly difficult
      procedures started using a rubber model, followed by 'open' and 'closed' rat
      models simulating laparoscopic conditions. MAIN OUTCOME MEASURES: The surgical
      skills of all participants were assessed before and after the laparoscopic
      training course by applying 5 defined tasks in a simulation trainer. As a control
      group, 8 surgical residents with the same amount of minimal-invasive training
      were tested after a 2-day interval. RESULTS: All participants of the laparoscopic
      training programme significantly improved their surgical skills for all 5 tasks
      (p < 0.05). In the control group only one of the 5 tasks was significantly
      improved after repetition. Participants of the complete training programme
      consistently improved their surgical skills significantly compared with the
      controls before and after repetition (p < 0.05). CONCLUSION: Surgical training in
      minimal-invasive techniques in the rat model is effective and reproducible
      especially to improve laparoscopic skills such as bimanual tissue handling, knot
      tying and microsurgical suturing.

PMID- 12182244
TI  - Hormonal changes related to reduced renal blood flow and low urine output under
      prolonged increased intra-abdominal pressure in pigs.
AB  - OBJECTIVE: To investigate effects of prolonged increased intra-abdominal pressure
      (IAP) on diuresis, renal blood flow, and hormones that influence renal function,
      in particular endothelin. DESIGN: Experimental study. SETTING: Haukeland
      University Hospital, Norway. ANIMALS: 21 domestic pigs. METHODS: The TAP was
      maintained at normal (n = 7) or at 20 mmHg (n = 7) or 30 mmHg (n = 7) for three
      hours. MAIN OUTCOME MEASURES: Urine output, renal venous pressure, renal artery
      blood flow (transit-time flowmetry), renal cortex blood flow (microspheres), and
      renin, aldosterone, atrial natriuretic factor (ANF), adrenaline, noradrenaline,
      cortisol, and endothelin-1 (ET-1) in renal venous blood. RESULTS: An IAP of 20
      mmHg was followed by no significant changes in the variables studied. An IAP of
      30mmHg was associated with anuria, considerably reduced renal blood flow and
      increased renal vascular resistance. The renin activity and the blood
      concentrations of ET-1, aldosterone, noradrenaline, adrenaline, and cortisol
      increased during the three hours that IAP was at 30 mmHg. CONCLUSION: An IAP of
      20 mmHg did not influence renal haemodynamics or diuresis. The low renal blood
      flow observed at an IAP of 30 mmHg probably results from reduced arteriovenous
      pressure difference and vasoconstriction. Increased concentrations of endothelin,
      angiotensin II, and noradrenaline may account for the vasoconstriction. The
      anuria can be explained by low renal blood flow and increased reabsorption of
      sodium in renal tubules caused by aldosterone.

PMID- 12182245
TI  - Injuries in 8927 patients admitted after motor-cycle crashes in Sweden 1987-1994
      inclusive.
AB  - OBJECTIVE: To discover morbidity and mortality rates after motor-cycle crashes on
      the national level in Sweden. DESIGN: Retrospective study. SETTING: Teaching
      hospital, Sweden. INTERVENTIONS: Extraction of data from International
      Classification of Diseases (ICD) codes E819C (motor-cycle drivers) and E819D
      (motor-cycle passengers) recorded in the Swedish Hospital Discharge Register
      (SHDR) between 1987 and 1994. MAIN OUTCOME MEASURES: Injury distribution, medical
      consequences, mortality, survival, and incidence by age, sex and geographical
      area. RESULTS: The number of people admitted to hospital after motor-cycle
      crashes decreased significantly during the period (from 1743 in 1987 to 1258 in
      1994, p < 0.001). The most frequent injuries among drivers and passengers alike
      were fractures of the legs, arms, and vertebrae, followed by injuries to the head
      and brain. The in-hospital mortality was lower among drivers (n = 172, 2.2%) than
      among passengers (n = 31,3.3%). CONCLUSION: The incidence of injuries after motor
      cyclist crashes decreased during the study period. The most common victims were
      young men with fractures and brain injuries. Those at most risk of dying were
      older passengers.

PMID- 12182246
TI  - Diagnosis and treatment of primary incarcerated lumbar hernia.

PMID- 12182247
TI  - Total thyroidectomy: the procedure of choice for multinodular goitre.

PMID- 12182248
TI  - Is total thyroidectomy a dangerous procedure outside a specialised thyroid
      surgical unit?

PMID- 12182249
TI  - The role of angiotensin II antagonism in type 2 diabetes mellitus: a review of
      renoprotection studies.
AB  - BACKGROUND: Diabetic nephropathy is the leading cause of end-stage renal disease
      (ESRD) in Western and Asian countries. Effective antihypertensive therapy reduces
      the rate of decline in renal function and postpones ESRD in patients with
      diabetic nephropathy. OBJECTIVE: This review presents evidence from studies on
      how blood pressure control, plasma glucose control, and the presence of
      proteinuria determine outcomes in diabetic patients. The role of angiotensin II
      (All) in the development of diabetic nephropathy and the reno- and
      cardiobeneficial effects of AII antagonism in patients with type 2 diabetes
      mellitus (DM-2) and diabetic nephropathy also are addressed. METHODS: Articles
      included in this review were found using a MEDLINE search for studies published
      from 1991 to 2001 and including the search terms diabetic nephropathy, type 2
      diabetes mellitus, microalbuminuria, proteinuria, angiotensin receptor blockade,
      angiotensin-converting enzyme inhibition, and cardiovascular disease. Articles
      reporting new data, new mechanisms, major clinical trials, and our own data were
      included. RESULTS: Recently, the Reduction of Endpoints in NIDDM (non-insulin
      dependent diabetes mellitus) with the Angiotensin II Antagonist Losartan (RENAAL)
      trial provided sufficient data to conclude that the blockade of the All AT1
      receptor with losartan confers renoprotection in patients with DM-2 and
      nephropathy. Similar results were obtained with irbesartan in the Irbesartan
      Diabetic Nephropathy Trial (IDNT) and the Irbesartan in Patients with Type 2
      Diabetes and Microalbuminuria study (IRMA 2). The results of RENAAL indicate that
      the renoprotective effects of losartan were attributable to effects beyond blood
      pressure control. In addition to the favorable impact of the All blockade on
      blood pressure and renal hemodynamics, the blockade of the growth-promoting,
      profibrotic, nonhemodynamic actions of AII also may be important for
      renoprotection. Intensive blood pressure control also confers cardiovascular
      protection in pa- tients with DM-2. Some studies suggest that the blockade of the
      renin-angiotensin system confers superior cardioprotective effects in patients
      with DM-2. The RENAAL study also showed cardioprotection with losartan, with an
      important reduction in the risk for first hospitalization for heart failure.
      CONCLUSION: Evidence supports the importance of an effective blockade of AII
      action for both reno- and cardioprotection in patients with DM-2.

PMID- 12182250
TI  - Efficacy of budesonide in inhaled corticosteroid-naive patients and patients with
      mild persistent asthma.
AB  - BACKGROUND: Patients with mild intermittent or mild persistent asthma represent
      70% of asthma sufferers. Inhaled corticosteroids (ICSs) are the mainstay of
      treatment for persistent asthma, although many of the early clinical studies of
      these drugs included only patients with moderate to severe asthma. OBJECTIVE:
      This article reviews the literature on the efficacy of budesonide in the
      treatment of mild persistent asthma, including newly diagnosed ICS-naive
      patients. METHODS: Published data were identified by a MEDLINE search of the
      English-language literature from 1992 to 2002 using the terms budesonide plus
      efficacy or safety, both with and without the termsfluticasone or beclomethasone.
      An AstraZeneca reference database was also used to identify publications from the
      same period. Controlled, randomized studies that included patients with mild
      persistent asthma and early-treatment intervention were selected for inclusion.
      RESULTS: Inhaled budesonide has been used for almost 20 years in the treatment
      and control of moderate to severe asthma. Studies involving patients with mild
      persistent asthma have demonstrated significant improvements in peak expiratory
      flow (PEF) rates (P < 0.01) and forced expiratory volume in I second (P < 0.016)
      values for adult, adolescent, and pediatric patients treated with budesonide
      compared with placebo. Budesonide therapy is effective when given once or twice
      daily via dry powder inhaler or nebulizer, even at a low starting dose (200
      microg/d). No significant adverse events have been reported with budesonide
      within the dose range used to treat mild persistent asthma (200 to 400 microg/d).
      Significant improvements in PEF rates (P < 0.01) and significant reductions in
      the risk of exacerbations and the number of days with poorly controlled asthma
      have been reported for ICS-naive patients treated with budesonide compared with
      placebo (both P < 0.001). In the primary care setting, mild persistent asthma may
      be undertreated. Patients with mild persistent asthma benefit significantly from
      early treatment with budesonide (P < 0.05). CONCLUSIONS: Budesonide is effective
      and well tolerated in the treatment of mild persistent asthma in adults and
      children, including many patients whose primary care physicians do not think they
      require daily ICS treatment.

PMID- 12182251
TI  - A multicenter, randomized, double-blind, placebo-controlled, 8-week trial of the
      efficacy and tolerability of once-daily losartan 100 mg/hydrochlorothiazide 25 mg
      and losartan 50 mg/hydrochlorothiazide 12.5 mg in the treatment of moderate-to
      severe essential hypertension.
AB  - BACKGROUND: Many patients with moderate-to-severe hypertension require multiple
      drug therapy to achieve blood-pressure goals. Fixed-dose combination therapy with
      losartan and hydrochlorothiazide may be useful in this population. OBJECTIVE:
      This study was conducted to obtain additional data on the antihypertensive
      efficacy and tolerability of once-daily, fixed-dose combinations of losartan and
      hydrochlorothiazide. METHODS: This was a multicenter, randomized, double-blind,
      parallel-group, placebo-controlled trial. Patients > or = 21 years of age with
      moderate-to-severe essential hypertension, defined as a mean trough sitting
      diastolic blood pressure (SiDBP) of 105 to 115 mm Hg, were randomly assigned in a
      2:2:1 ratio to receive losartan 100 mg/hydrochlorothiazide 25 mg (L100/25),
      losartan 50 mg/hydrochlorothiazide 12.5 mg (L50/12.5), or placebo (PBO) once
      daily for 8 weeks. The primary efficacy measurement was the mean change from
      baseline in trough SiDBP in the L100/25 versus L50/12.5 treatment groups.
      Responders were defined as patients with mean trough SiDBP <90 mm Hg or a > or =
      10-mm Hg decrease in mean trough SiDBP. RESULTS: A total of 446 patients were
      randomly assigned to receive L100/25 (n = 173), L50/12.5 (n = 184), or PBO (n =
      89). At week 8, mean trough SiDBP was significantly lower than at baseline in the
      L100/25 (-17.5 mm Hg), L50/12.5 (-15.2 mm Hg), and PBO groups (-8.5 mm Hg) (all P
      < 0.001). The difference between the active-treatment groups was statistically
      significant (-2.2 mm Hg; 95% Cl, range -3.8 to -0.6) (P = 0.006), as was the
      difference between the L100/25 and PBO groups (-9.0 mm Hg; 95% CI, range -I1.0 to
      -7.0) (P < 0.001) and the L50/12.5 and PBO groups (-6.7 mm Hg; 95% CI, range -8.7
      to -4.8) (P < 0.001). At week 8, the percentages of responders were 86.7% (144 of
      166), 78.9% (142 of 180), and 50.0% (42 of 84) in the L100/25, L50/12.5, and PBO
      groups, respectively. The incidence of adverse experiences (AEs) was 34.7% (60 of
      173) in the L100/25 group, 23.9% (44 of 184) in the L50/12.5 group, and 32.6% (29
      of 89) in the PBO group. The incidence of drug-related AEs was similar among the
      treatment groups (L100/25, 7.5% [13 of 173]; L50/12.5, 7.1% [13 of 184]; and PBO,
      11.2% [10 of 89]). CONCLUSIONS: This study demonstrates the antihypertensive
      efficacy and tolerability of the once-daily, fixed-dose combination L50/12.5 in
      patients with moderate-to-severe essential hypertension. In this study, L100/25
      provided additional anti-hypertensive efficacy beyond that of L50/12.5 (and both
      were more efficacious than PBO). Approximately 4 of 5 patients (78.9%) treated
      with L50/12.5 responded to therapy, as did nearly 9 of 10 patients (86.7%)
      treated with L100/25. The tolerability profiles of L50/12.5 and L100/25 were
      similar to that of PBO.

PMID- 12182252
TI  - The effect of ranitidine on the pharmacokinetics of rosiglitazone in healthy
      adult male volunteers.
AB  - BACKGROUND: Rosiglitazone is an insulin-sensitizing oral agent in the
      thiazolidinedione class used to treat patients with type 2 diabetes mellitus. It
      binds to peroxisome proliferator-activated receptor gamma in liver, muscle, and
      adipose tissue. Ranitidine, a histamine2-receptor antagonist, may be prescribed
      for patients with type 2 diabetes and esophageal symptoms such as heartburn. By
      raising gastrointestinal pH levels, ranitidine may affect the bioavailability of
      coadministered drugs. OBJECTIVES: This article presents the absolute
      bioavailability of rosiglitazone, as well as the effects of ranitidine on the
      pharmacokinetics of rosiglitazone. METHODS: Healthy men were enrolled in a
      randomized, open-label, 4-period, period-balanced crossover study of
      rosiglitazone and ranitidine. All individuals received each of 4 regimens
      successively, separated by a 4-day washout period: a single IV dose of
      rosiglitazone 2 mg administered alone over 1 hour; a single IV dose of
      rosiglitazone 2 mg administered over 1 hour on the fourth day of treatment with
      oral ranitidine 150 mg given every 12 hours; a single oral dose of rosiglitazone
      4 mg alone; and a single oral dose of rosiglitazone 4 mg on the fourth day of
      treatment with oral ranitidine 150 mg given every 12 hours. The primary end point
      was dose-normalized area under the plasma concentration-time curve from time 0 to
      infinity (AUC(0-infinity)). Maximum observed plasma concentration (Cmax), the
      time at which Cmax occurred (Tmax), plasma clearance (CL), steady-state volume of
      distribution (Vss), and terminal elimination half-life (t 1/2) were also
      assessed. RESULTS: Twelve individuals were enrolled. The absolute bioavailability
      of rosiglitazone was 99%. For AUC(0-infinity), the point estimate and the
      associated 95% CI for the ratio of ranitidine + IV rosiglitazone to IV
      rosiglitazone alone was 1.02 (range, 0.88-1.20). With oral rosiglitazone, the
      AUC(0-infinity) point estimate (95% CI) for the ratio of ranitidine +
      rosiglitazone to rosiglitazone alone was 0.99 (range, 0.85-1.16). Cmax, Tmax, t
      1/2, Vss and CL of rosiglitazone, whether administered orally or intravenously,
      were unaffected by ranitidine. Oral and IV rosiglitazone were associated with a
      favorable safety profile and were well tolerated with or without concurrent
      ranitidine treatment. CONCLUSIONS: In this study of 12 healthy adult male
      volunteers, the absolute bioavailability of rosiglitazone was 99%, and the oral
      and IV single-dose pharmacokinetics of rosiglitazone were unaltered by concurrent
      treatment with ranitidine.

PMID- 12182253
TI  - A randomized, double-blind, placebo-controlled comparison of the analgesic
      efficacy, onset of action, and tolerability of ibuprofen arginate and ibuprofen
      in postoperative dental pain.
AB  - BACKGROUND: Because of its enhanced pharmacokinetic characteristics, ibuprofen
      arginate might be expected to provide faster pain relief than standard ibuprofen
      formulations in patients experiencing acute pain. OBJECTIVE: This study assessed
      the analgesic efficacy, speed of onset, and tolerability of ibuprofen arginate
      compared with a commercially available form of ibuprofen in patients with
      postoperative dental pain. METHODS: Patients were randomized to receive ibuprofen
      arginate 200 or 400 mg, ibuprofen 200 or 400 mg, or placebo in this multicenter,
      double-blind, double-dummy, parallel-group trial. Patients were observed for 6
      hours after administration of a single dose of study medication. A repeated-dose,
      open-label phase followed. Pain intensity and pain relief were measured using
      traditional verbal descriptor scales; onset of analgesia was assessed using 2
      stopwatches to measure the time to achievement of specific pain relief criteria.
      RESULTS: A total of 498 patients (219 men, 279 women; mean age, 21.5 years)
      participated in this study. Baseline pain was moderate in 388 patients (78%) and
      severe in 110 patients (22%). Meaningful pain relief was reached after a median
      of 29 and 28 minutes with ibuprofen arginate 200 and 400 mg, respectively, and
      after 52 and 44 minutes with ibuprofen 200 and 400 mg, respectively (all, P <
      0.05). The percentages of patients who achieved meaningful pain relief within the
      first hour after treatment were 77.6% and 83.7% for ibuprofen arginate 200 and
      400 mg, respectively, 61.0% and 63.0% for ibuprofen 200 and 400 mg, respectively,
      and 39.8% for placebo. The differences between ibuprofen arginate and ibuprofen
      were statistically significant (both doses, P < 0.05). Significantly greater
      numbers of patients achieved meaningful pain relief with ibuprofen arginate 400
      mg compared with placebo from 20 minutes through 6 hours and with ibuprofen
      arginate 200 mg from 30 minutes through 6 hours (P < 0.05). Compared with
      placebo, a greater number of patients achieved meaningful pain relief with
      ibuprofen 400 mg from 45 minutes through 6 hours; with ibuprofen 200 mg. the
      corresponding interval was from I through 6 hours. After the first hour, pain
      reduction was similar for the similar doses of the 2 ibuprofen preparations.
      Median remedication times with both doses of ibuprofen arginate were similar to
      those with both doses of ibuprofen, ranging from 4.0 to 5.2 hours. Adverse-event
      profiles were similar between the 2 active medications. CONCLUSIONS: Ibuprofen
      arginate was effective in this population of patients experiencing moderate to
      severe pain after surgical extraction of > or = 1 impacted third molar, with 16
      to 24 minutes' faster time to meaningful pain relief than with ibuprofen. The 2
      formulations had similar tolerability profiles.

PMID- 12182256
TI  - A randomized, double-blind comparison of a clindamycin phosphate/benzoyl peroxide
      gel formulation and a matching clindamycin gel with respect to microbiologic
      activity and clinical efficacy in the topical treatment of acne vulgaris.
AB  - BACKGROUND: One approach to suppressing the overgrowth of antibiotic-resistant
      bacteria is to develop combination products composed of active constituents with
      complementary but distinct mechanisms of antibacterial action. OBJECTIVE: The
      purpose of this study was to compare the antimicrobial and clinical efficacy and
      tolerability of clindamycin phosphate 1%/benzoyl peroxide 5% gel formulation with
      matching clindamycin 1% gel in the treatment of acne vulgaris. METHODS: This 16
      week, single-center, double-blind, randomized, parallel-group study compared the
      combination gel with clindamycin monotherapy applied BID in patients 13 to 30
      years of age with mild to moderate acne and facial Propionibacterium acnes counts
      > or = 10(4) colony-forming units per square centimeter of skin. RESULTS: Seventy
      nine patients were enrolled and randomly assigned to receive the combination gel
      (n = 40) or clindamycin monotherapy (n = 39). Seventy patients (50 males, 20
      females; mean age, 18.2 years) were included in the intent-to-treat group. The
      combination gel treatment produced significantly greater reductions (P < or =
      0.046) from baseline in total lesion counts and in numbers of inflammatory
      lesions and comedones compared with clindamycin monotherapy. Greater reductions
      in the severity of acne also were observed in the physician's and patient's
      Clinical Global Improvement scale scores and in other secondary efficacy
      measurements. Reductions in clindamycin-resistant P acnes counts were observed
      relative to baseline in the combination gel group; in contrast, P acnes counts
      increased by >1,600% in the clindamycin monotherapy group at week 16 (P = 0.018
      vs combination gel). Reductions in inflammatory (r2 = 0.31; P = 0.016) and total
      (r2 = 0.28; P = 0.027) lesions were correlated with decreases in clindamycin
      resistant bacteria. Also, significant correlations were observed between the
      percent change from baseline in total lesion counts (r2 = 0.44; P < 0.001) and
      comedo counts (r2 = 0.50; P < 0.001) and the log10 change from baseline in total
      P acnes counts. CONCLUSIONS: The total P acnes count (P = 0.002) and the
      clindamycin-resistant P acnes count (P = 0.018) were significantly reduced after
      16 weeks of treatment with combination gel compared with clindamycin monotherapy.
      These reductions in total P acnes and clindamycin-resistant P acnes counts
      correlated with reductions in total acne lesions.

PMID- 12182255
TI  - Efficacy and tolerability of a "suprabioavailable" formulation of fenofibrate in
      patients with dyslipidemia: a pooled analysis of two open-label trials.
AB  - BACKGROUND: Newer fibrates such as micronized fenofibrate lower triglyceride (TG)
      levels, raise high-density lipoprotein cholesterol (HDL-C) levels, and lower
      fibrinogen levels, in addition to markedly lowering levels of total cholesterol
      (TC) and low-density lipoprotein cholesterol (LDL-C). A new microcoated
      "suprabioavailable" formulation of fenofibrate has demonstrated a superior
      pharmacokinetic profile compared with micronized fenofibrate 200 mg/d and may
      effectively reduce cardiovascular risk factors at the lower dose of 160 mg/d.
      OBJECTIVE: The goal of this study was to assess the efficacy and tolerability of
      the suprabioavailable" formulation of fenofibrate in patients with type IIa, type
      IIb, or type IV dyslipidemia. METHODS: This was a pooled analysis of data from 2
      unpublished multicenter, open-label trials with a common protocol. After a 4-week
      washout period, patients with dyslipidemias not corrected by diet alone were
      assigned to receive microcoated fenofibrate 160 mg/d for 12 weeks. Changes in
      lipid profiles and safety variables (vital signs, body weight, and laboratory
      measures) were monitored throughout the study, and adverse events occurring
      between visits 1 and 5 were recorded by the study investigators. RESULTS: The 2
      trials included 375 men and women (mean age, 55.2 years) with type IIa (n = 158),
      type IIb (n = 195), type IV (n = 21), or other (n = 1) dyslipidemias. At end
      point. HDL-C levels in patients with type IIa, IIb, or IV dyslipidemia were
      increased by a respective 10.9% (P < 0.001), 16.1% (P < 0.001), and 12.1% (P <
      0.05), whereas TG levels were decreased by a respective 27.7% (P < 0.001), 46.4%
      (P < 0.001), and 40.2% (P < 0.05). In patients with type IIa or IIb dyslipidemia,
      TC decreased (-14.3% in each group), LDL-C decreased (-20.6% and -13.2%,
      respectively), and the LDL-C/HDL-C ratio decreased (-26.7% and -22.0%) (all, P <
      0.001). Overall, 121 of 375 (32.3%) patients experienced > or = adverse event
      (AE) (202 nonserious, 8 serious). Of these, 10.1% were judged to be possibly drug
      related. The most common nonserious AEs were those affecting the body as a whole
      (2.7% of patients) and the digestive system (5.3% of patients). No serious AE was
      considered drug related. CONCLUSIONS: The new "suprabioavailable" microcoated,
      micronized formulation of fenofibrate appears to maintain the good efficacy and
      safety profile of micronized fenofibrate. In the study population with moderate
      dyslipidemia (types IIa and IIb), it promoted beneficial changes in major lipid
      risk factors for cardiovascular disease.

PMID- 12182254
TI  - Pharmacokinetics and pharmacodynamics of piperacillin/tazobactam when
      administered by continuous infusion and intermittent dosing.
AB  - BACKGROUND: Although intermittent bolus dosing is currently the standard of
      practice for many antimicrobial agents, beta-lactams exhibit time-dependent
      bacterial killing. Maximizing the time above the minimum inhibitory concentration
      (MIC) for a pathogen is the best pharmacodynamic predictor of efficacy. Use of a
      continuous infusion has been advocated for maximizing the time above the MIC
      compared with intermittent bolus dosing. OBJECTIVE: This study compared the
      pharmacokinetics and pharmacodynamics of piperacillin/tazobactam when
      administered as an intermittent bolus versus a continuous infusion against
      clinical isolates of Pseudomonas aeruginosa and Klebsiella pneumoniae. METHODS:
      Healthy volunteers were randomly assigned to receive piperacillin 3 g/ tazobactam
      0.375 g q6h for 24 hours, piperacillin 6 g/tazobactam 0.75 g continuous infusion
      over 24 hours, and piperacillin 12 g/tazobactam 1.5 g continuous infusion over 24
      hours. Five clinical isolates each of P aeruginosa and K pneumoniae were used for
      pharmacodynamic analyses. RESULTS: Eleven healthy subjects (7 men, 4 women; mean
      +/- SD age, 28 +/- 4.7 years) were enrolled. Mean steady-state serum
      concentrations of piperacillin were 16.0 +/- 5.0 and 37.2 +/- 6.8 microg/mL with
      piperacillin 6 and 12 g, respectively. Piperacillin/tazobactam 13.5 g continuous
      infusion (piperacillin 12 g/tazobactam 1.5 g) was significantly more likely to
      produce a serum inhibitory titer > or = 1:2 against P aeruginosa at 24 hours than
      either the 6.75 g continuous infusion (piperacillin 6 g/tazobactam 0.75 g) or
      3.375 g q6h (piperacillin 3 g/ tazobactam 0.375 g). There were no statistical
      differences against K pneumoniae between regimens. The median area under the
      inhibitory activity-time curve (AUIC) for the 13.5 g continuous infusion was
      higher than that for 3.375 g q6h and the 6.75 g continuous infusion against both
      P aeruginosa and Kpneumoniae (P < or = 0.007, 13.5 g continuous infusion and
      3.375 g q6h vs 6.75 g continuous infusion against K pneumoniae). The percentage
      of subjects with an AUIC > or = 125 was higher with both 3.375 g q6h and the 13.5
      g continuous infusion than with the 6.75 g continuous infusion against P
      aeruginosa and K pneumoniae (both, P < 0.001 vs 6.75 g continuous infusion
      against K pneumoniae). CONCLUSIONS: Piperacillin 12 g/tazobactam 1.5 g continuous
      infusion consistently resulted in serum concentrations above the breakpoint for
      Enterobacteriaceae and many of the susceptible strains of P aeruginosa in this
      study in 11 healthy subjects. Randomized controlled clinical trials are warranted
      to determine the appropriate dose of piperacillin/tazobactam.

PMID- 12182257
TI  - Randomized, double-blind, multicenter comparison of oral cefditoren 200 or 400 mg
      BID with either cefuroxime 250 mg BID or cefadroxil 500 mg BID for the treatment
      of uncomplicated skin and skin-structure infections.
AB  - BACKGROUND: Uncomplicated skin and skin-structure infections are commonly
      observed in medical practice. Because these infections typically are confined to
      the superficial layers and seldom lead to the destruction of skin structures and
      resultant systemic dissemination, in general they can be treated with an oral
      antibiotic with potent microbiologic activity against gram-positive pathogens.
      OBJECTIVE: This paper compares the efficacy and tolerability of 3 beta-lactam
      antibiotics in patients with uncomplicated skin and skin-structure infections.
      METHODS: Two double-blind, multicenter, parallel-group studies were conducted, in
      which patients aged > or = 12 years with uncomplicated skin and skin-structure
      infections were randomized to receive cefditoren 200 or 400 mg, cefuroxime 250
      mg, or cefadroxil 500 mg, each BID for 10 days. Study 1 compared cefditoren with
      cefuroxime; Study 2 compared cefditoren with cefadroxil. Clinical and
      microbiologic responses were assessed at a posttreatment visit (within 48 hours
      of treatment completion) and test-of-cure visit (7-14 days after treatment
      completion). Patients were monitored closely throughout the study with the use of
      physical examinations, clinical laboratory tests, and assessment of adverse
      events. RESULTS: A total of 1,685 patients (855 males, 830 females; mean age,
      41.1 years [range, 12-95 years]) were enrolled. Within both studies, the 3
      treatment groups were similar at baseline based on demographic characteristics
      and types of infection. Cellulitis (26%), wound infection (25%), and simple
      abscess (15%) were the most common infections. Clinical cure rates at the test-of
      cure visit were 85% (443/523) for cefditoren 200 mg, 83% (427/516) for cefditoren
      400 mg, 88% (234/265) for cefuroxime, and 85% (211/248) for cefadroxil. At the
      test-of-cure visit, cefditoren 200 mg had eradicated significantly fewer of the
      causative pathogens isolated before treatment in microbiologically evaluable
      patients than did cefuroxime in Study 1 (P = 0.043) but significantly more of the
      pathogens than did cefadroxil in Study 2 (P = 0.018). Eradication rates for the
      most commonly isolated pathogens were generally similar in the 3 treatment groups
      in both studies, with the only significant difference favoring cefditoren 200 and
      400 mg over cefadroxil for Peptostreptococcus species in Study 2 (P = 0.016 and P
      = 0.003, respectively). A minority of patients (< or = 5% in any treatment group)
      discontinued study-drug treatment prematurely due to a treatment-related adverse
      event, with statistically higher rates for cefditoren 400 mg than for cefditoren
      200 mg and the comparator cephalosporins (each P < 0.05). All 3 cephalosporins
      were generally well tolerated. Most adverse events (>93%) were categorized as
      mild to moderate, with the most common being diarrhea, nausea, and headache.
      CONCLUSION: In this population of patients with uncomplicated skin and skin
      structure infections, including those due to Staphylococcus aureus or
      Streptococcus pyogenes, the clinical cure rate and tolerability of cefditoren
      were comparable to those of cefuroxime and cefadroxil.

PMID- 12182258
TI  - Double-blind, placebo-controlled, dose-ranging study of ramosetron for the
      prevention of nausea and vomiting after thyroidectomy.
AB  - BACKGROUND: Patients receiving general anesthesia during thyroidectomy have a
      high risk for postoperative nausea and vomiting. OBJECTIVE: This prospective,
      randomized, double-blind, placebo-controlled, dose-ranging study was undertaken
      to assess the efficacy and safety of ramosetron, a selective 5-hydroxytryptamine
      type 3-receptor antagonist, in preventing nausea and vomiting after
      thyroidectomy. METHODS: Standard general anesthetic technique and postoperative
      analgesia were employed. Patients undergoing thyroidectomy were randomized to
      receive IV ramosetron 0.15, 0.3, or 0.6 mg or placebo at completion of the
      procedure. During the first 48 hours after anesthesia, episodes of emesis and
      adverse events were assessed by nursing staff who were blinded to patients'
      treatment assignment. RESULTS: Eighty patients (22 men, 58 women; age range, 28
      63 years; weight range, 37-91 kg) were enrolled in the study. There were no
      differences in demographic characteristics between treatment groups. The numbers
      of patients who were emesis free (no nausea, retching, or vomiting) 0 to 24 hours
      after anesthesia were 10 of 20 (50%) with ramosetron 0.15 mg, 17 of 20 (85%) with
      ramosetron 0.3 mg, 18 of 20 (90%) with ramosetron 0.6 mg, and 8 of 20 (40%) with
      placebo. The corresponding numbers 24 to 48 hours after anesthesia were 11 of 20
      (55%), 18 of 20 (90%), 18 of 20 (90%), and 9 of 20 (45%). At both time points,
      only the values for ramosetron 0.3 and 0.6 mg were statistically significant
      versus placebo (P < or = 0.001). No clinically serious adverse events were
      observed in any group. CONCLUSIONS: In this population of patients receiving
      general anesthesia while undergoing thyroidectomy, ramosetron 0.3 mg was
      effective in preventing postoperative nausea and vomiting 0 to 48 hours after
      anesthesia. Increasing the dose to 0.6 mg provided no demonstrable benefit.

PMID- 12182259
TI  - A retrospective assessment of the effectiveness of fenofibrate 267 mg on high
      density lipoprotein cholesterol levels in patients attending a lipid clinic.
AB  - BACKGROUND: A high-density lipoprotein cholesterol level (HDL-C) <1 mmol/L is
      associated with increased cardiovascular morbidity and mortality. In clinical
      trials, fibrates have been shown to increase levels of HDL-C, with subsequent
      reduction in cardiovascular risk. OBJECTIVE: This study evaluated the use of
      fenofibrate 267 mg/d in a routine lipid clinic setting to determine how much HDL
      C could be increased in everyday clinical practice. METHODS: Blood samples from
      patients who had taken fenofibrate 267 mg/d between 1998 and 2001 at the Lipid
      Clinic, Charing Cross Hospital, London, United Kingdom, were analyzed for changes
      in total cholesterol (TC), HDL-C, and triglycerides during follow-up. RESULTS:
      Sixty-five consecutive patients (49 men, 16 women; mean age, 54 +/- 1.2 years)
      were included in the study. The follow-up period ranged from 1 to 36 months
      (mean, 9.6 months +/- 26.7 days). Patients achieved a 6% overall increase in HDL
      C, from 0.91 +/- 0.03 mmol/L to 0.97 +/- 0.03 mmol/L (P = 0.016). The TC/HDL-C
      ratio decreased by 21% from 7.0 +/- 0.3 mmol/L to 5.5 +/- 0.2 mmol/L (P < 0.001).
      Patients with lower levels of HDL-C at baseline (<0.9 mmol/L) showed the most
      improvement, with an 8% increase (P < 0.05). Twenty-eight patients (43%) reached
      a target HDL-C posttherapy value >1.0 mmol/L. Thirty-nine patients (responders)
      had increases in their HDL-C levels; 26 patients (nonresponders) had decreases or
      no change in their HDL-C levels. For the 26 (40%) patients in whom HDL-C did not
      increase, the TC/HDL-C ratio decreased by 12% from 6.5 +/- 0.3 mmol/L to 5.7 +/-
      0.3 mmol/L (P = 0.003). CONCLUSIONS: Fenofibrate 267 mg/d is well tolerated and
      can achieve significant increases in HDL-C levels in clinical practice. However,
      these results should be confirmed in a larger routine clinical setting because of
      the discrepancies between the results of some clinical trials.

PMID- 12182260
TI  - Comparison of the efficacy of combined fluticasone propionate and olopatadine
      versus combined fluticasone propionate and fexofenadine for the treatment of
      allergic rhinoconjunctivitis induced by conjunctival allergen challenge.
AB  - BACKGROUND: One approach to treating allergic rhinoconjunctivitis is the
      concomitant use of an intranasal spray such as fluticasone propionate to
      alleviate nasal symptoms and a topical or systemic agent to relieve ocular
      symptoms. It has not yet been determined whether a topical or systemic agent is
      more effective for the latter purpose. OBJECTIVE: This study compared the
      efficacy of combined use of fluticasone and olopatadine with combined use of
      fluticasone and fexofenadine in the treatment of the signs and symptoms of
      allergic rhinoconjunctivitis. METHODS: This 2-site, randomized, double-masked,
      placebo-controlled, parallel-group study employed the conjunctival allergen
      challenge (CAC) model, a standardized method of inducing ocular and nasal signs
      and symptoms of allergic rhinoconjunctivitis. At visit 1, subjects underwent CAC
      to determine the dose of allergen required to elicit a positive reaction. The
      allergen dose was confirmed at visit 2, and, according to a randomization
      schedule, subjects were dispensed fluticasone, olopatadine, and placebo pill;
      fluticasone, fexofenadine, and tear substitute; or placebo nasal spray, placebo
      pill, and tear substitute. CAC took place at visit 3, after patients had used the
      assigned medications for 2 weeks. Study medication was instilled 2 hours before
      CAC, after which allergic signs and symptoms were graded on standardized scales.
      The primary efficacy variables were ocular itching, ocular redness, and overall
      nasal symptoms. RESULTS: Eighty subjects completed the study: 30 received
      fluticasone and olopatadine, 30 fluticasone and fexofenadine, and 20 placebo.
      Women constituted 63.8% of the study population and men 36.3%; 91.3% were white,
      3.8% black, 2.5% Hispanic, 1.3% Asian, and 1.3% other. Concomitant use of
      fluticasone and olopatadine produced significantly greater improvements in ocular
      itching at 3 and 7 minutes after CAC compared with fluticasone and fexofenadine
      (P < 0.05). There were no significant differences in redness scores between
      groups; however, concomitant use of fluticasone and olopatadine produced
      significantly greater improvements in redness at 2 time points in each of the 3
      vessel beds (ciliary, conjunctival, and episcleral) compared with placebo, and
      fluticasone and fexofenadine produced significantly greater improvement in
      redness at 1 time point in I vessel bed compared with placebo (both comparisons,
      P < 0.05). The 2 treatments had similar effects on total nasal symptom efficacy
      scores. CONCLUSIONS: In this study, concomitant use of the topical agents
      fluticasone and olopatadine was more effective than concomitant use of
      fluticasone plus fexofenadine for overall treatment of the signs and symptoms of
      induced allergic rhinoconjunctivitis.

PMID- 12182261
TI  - Comparison of the effects of losartan and atenolol on common carotid artery
      intima-media thickness in patients with hypertension: results of a 2-year, double
      blind, randomized, controlled study.
AB  - BACKGROUND: Hypertension induces progressive pathologic changes in the arterial
      wall. Experimental findings suggest that these changes, which include intima
      media thickening, may be mediated, at least in part, by angiotensin II (AII).
      OBJECTIVE: The Losartan Vascular Regression Study (LAARS) was a double-blind,
      parallel-group, randomized, controlled, multicenter study designed to compare the
      effects of the AII antagonist losartan and the beta-blocker atenolol on
      ultrasonographically determined intimamedia thickness (IMT) of the common carotid
      artery (CCA) in patients with mild to moderate essential hypertension. METHODS:
      The primary end point of the study was the yearly rate of change (YRC) from
      baseline of the mean IMT of the CCA (CCA-IMT(mean)) averaged over 2 years of
      treatment. Secondary end points included IMT of the common femoral artery and
      sitting systolic and diastolic blood pressures (SiSBP/SiDBP). Safety assessments
      of losartan and atenolol were made by statistical and clinical review of the
      incidence of adverse experiences as well as review of vital signs and laboratory
      values. A total of 414 patients with essential hypertension were screened for
      study inclusion at 36 study centers in Germany and Brazil. Patients received
      losartan (50 mg once daily) or atenolol (50 mg once daily) for 24 months. Target
      blood pressure (SiSBP/SiDBP <140/<90 mm Hg) was achieved by adding
      hydrochlorothiazide 12.5 mg once daily, doubling the dose of study drug, or
      adding an open-label calcium channel blocker sequentially, as needed. RESULTS: Of
      the original 414 patients screened, 280 hypertension patients (SiDBP 95-115 mm
      Hg), aged 35 to 65 years, with an IMT of 0.8 to 1.5 mm of the right or left CCA,
      were randomized to treatment with either losartan (n = 142) or atenolol (n =
      138). Both losartan and atenolol therapy produced comparable reductions in CCA
      IMTmean over 24 months compared with baseline; the average YRC was -0.038 +/-
      0.004 mm/y (P < or = 0.001) for losartan and -0.037 +/- 0.004 mm/y (P < or =
      0.001) for atenolol. There were no significant differences between groups.
      Losartan showed a greater reduction of femoral artery IMT than did atenolol; the
      average YRC was -0.024 mm/y (P < or = 0.05) for losartan and -0.017 mm/y for
      atenolol (P = NS), with no significant difference between groups. Both agents
      produced similar significant reductions in SiSBP and SiDBP and were generally
      well tolerated. Approximately 7% of losartan patients had drug-related clinical
      adverse events, compared with 12% of atenolol patients. CONCLUSIONS: The findings
      of LAARS, the first large study with an AII antagonist that examined IMT, suggest
      that AII antagonism reverses the early stages of vascular hypertrophy in patients
      with hypertension. Further studies are needed to delineate the relative
      importance of AII antagonism versus blood pressure reduction per se in mediating
      the beneficial vascular effects of losartan.

PMID- 12182262
TI  - Efficacy of venlafaxine in patients with major depressive disorder who have
      unsustained or no response to selective serotonin reuptake inhibitors: an open
      label, uncontrolled study.
AB  - BACKGROUND: Approximately half of patients who are prescribed selective serotonin
      re-uptake inhibitors (SSRIs) either do not respond to treatment or do not
      experience a sustained response. OBJECTIVE: The purpose of this study was to
      assess the efficacy of venlafaxine immediate-release (IR) and extended-release
      (XR) in outpatients who either did not respond to SSRI treatment or did not
      maintain a sustained response. METHODS: Outpatients who met the Diagnostic and
      Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) criteria for
      major depressive disorder who were previously treated with an SSRI (fluoxetine >
      or = 20 mg/d; sertraline > or = 50 mg/d; paroxetine > or = 20 mg/d) for > or = 6
      weeks, but demonstrated an inadequate or unsustained response, were switched to
      venlafaxine (IR or XR formulation, 50-400 mg/d, titrated from 37.5 mg/d) for > or
      = 6 weeks. Response at 6 to 8 weeks was defined as total score < or = 10 on the
      modified 25-item Hamilton Depression (HAM-D25) rating scale or total score > or =
      5 on the 21-item Patient Global Improvement (PGI-21) scale. Remission was defined
      as a HAM-D25 total score < or = 8 or PGI-21 score > or = 7. Tests were
      administered by an unblinded, board-certified psychiatrist. RESULTS: A total of
      73 patients (54 women, 19 men; mean age, 38.6 years) were enrolled and treated
      with venlafaxine IR (n = 63) or venlafaxine XR (n = 10); 33 were SSRI
      nonresponders and 36 had an unsustained response to SSRI treatment. Four patients
      receiving venlafaxine IR discontinued due to drug-related adverse events
      (agitation, sedation, or nausea). Data from these patients were excluded from the
      analysis. After 6 to 8 weeks of treatment, 94.2% (65/69) of patients were
      considered responders (HAM-D25 or PGI-21 criteria); 91.3% (63/69) of patients
      responded to treatment as assessed by both measures. Eighty-seven percent (60/69)
      and 85.5% (59/69) of patients achieved remission based on HAM-D,5 and PGI-21
      criteria, respectively. Response/remission rates were comparable among patients
      treated with SSRIs, regardless of whether patients had failed to respond to
      treatment with 1 or 2 SSRIs. CONCLUSION: Venlafaxine IR/venlafaxine XR may be
      effective in outpatients with major depressive disorder who do not respond or
      have an unsustained response to SSRIs. However, randomized, controlled trials are
      needed before any conclusions can be drawn about the efficacy of this agent in
      this population.

PMID- 12182263
TI  - Pharmaceutical patents and price controls.
AB  - BACKGROUND: Since 1995, every member-country of the World Trade Organization
      (WTO) has agreed to honor a 20-year patent-life, from the date of a
      pharmaceutical company's application for the patent, in the country of
      application. Patent protection retards competitive imitation of an invented
      product. This kind of protection is particularly important for pharmaceuticals,
      because pharmaceuticals that are not derived from biotechnology can be imitated
      easily and inexpensively. The economic function of a patent is to allow a period
      of above-normal profits for a technically and commercially successful product;
      these profits stimulate further investment and invention. However, direct price
      controls, or permutations of direct price controls on pharmaceutical compounds,
      can fully or partially circumvent the economic intent of patent agreements.
      OBJECTIVE: This paper formulates an economic model that takes into account demand
      and cost/supply dimensions of the output and pricing of a hypothetical
      pharmaceutical, extrapolating about the respective effects of direct price
      controls and lack of price controls, and describing permutations of direct price
      controls in different countries. RESULTS: The pharmaceutical industry depends on
      patents to fund the development and introduction of new products. A country can
      indirectly circumvent the economic logic of a patent by using price controls, but
      it cannot shift the economic costs of such a policy to another country that does
      not use price controls. Instead, less money is available for research and
      development (R&D). CONCLUSIONS: Pharmaceutical price controls allow some
      countries to avoid the constraints of patent agreements without breaking those
      agreements outright. This, in turn, reduces the amount of profit available for
      further R&D, which is a detriment to consumers worldwide.

PMID- 12182264
TI  - Reducing STD and HIV risk behavior of substance-dependent adolescents: a
      randomized controlled trial.
AB  - A randomized controlled trial assessed 3 interventions designed to increase safer
      sex behaviors of substance-dependent adolescents. Participants (N = 161) received
      12 sessions of either a health information intervention (I only), information
      plus skills-based safer sex training (I + B), or the same experimental condition
      plus a risk-sensitization manipulation (I + M + B). The I + B and I + M + B
      conditions, as compared with the I only condition, (a) produced more favorable
      attitudes toward condoms; (b) reduced the frequency of unprotected vaginal sex;
      and (c) increased behavioral skill performance, frequency of condom-protected
      sex, percentage of intercourse occasions that were condom protected, and number
      of adolescents who abstained from sex. The intervention that included the risk
      sensitization procedure was more resistant to decay. An unexpected finding was
      that the I + B and I + M + B conditions produced substantial increases in sexual
      abstinence.

PMID- 12182265
TI  - Does imaginal exposure exacerbate PTSD symptoms?
AB  - Symptom exacerbation (i.e., treatment side effects) has often been neglected in
      the psychotherapy literature. Although prolonged exposure has gained empirical
      support for the treatment of chronic posttraumatic stress disorder (PTSD), some
      have expressed concem that imaginal exposure, a component of this therapy, may
      cause symptom exacerbation, leading to inferior outcome or dropout. In the
      present study, symptom exacerbation was examined in 76 women with chronic PTSD.
      To define a "reliable" exacerbation, we used a method incorporating the standard
      deviation and test-retest reliability of each outcome measure. Only a minority of
      participants exhibited reliable symptom exacerbation. Individuals who reported
      symptom exacerbation benefited comparably from treatment. Further, symptom
      exacerbation was unrelated to dropout. Thus, although a minority of individuals
      experienced a temporary symptom exacerbation, this exacerbation was unrelated to
      outcome.

PMID- 12182266
TI  - Is paranoid status prognostic of good outcomes? It depends.
AB  - Better outcomes for psychiatric inpatients classified as paranoid rather than
      nonparanoid could be due to group differences in disability levels created by
      traditional classification approaches. Paranoid functioning, per se, may not
      predict good institutional outcomes. The authors retrieved community outcome data
      for 469 inpatients from 19 wards, a subsample of participants that had been
      previously examined during their inpatient stay. Paranoid groups showed better
      community outcomes as an artifact of differences in disability levels when
      classifications were based on the traditional approach that requires a
      predominance of paranoid over nonparanoid behavior. No differential outcomes
      appeared when classifications were based on dimensionally measured paranoid
      functioning alone. In fact, dispositions of patients suggest that staff view
      paranoid behavior as a negative rather than positive prognostic indicator.

PMID- 12182267
TI  - Correlates of body image dissatisfaction among overweight women seeking weight
      loss.
AB  - Predictors of body image dissatisfaction (BID) among obese people are poorly
      understood. In 79 obese women seeking weight reduction, associations with BID of
      self-esteem, youth teasing, adult teasing, and internalization of sociocultural
      appearance standards (ISAS) were studied. Analyses revealed that only self
      esteem, adult teasing, and ISAS predicted BID. Results highlight the importance
      of adulthood self-esteem and interpersonal-cultural context--rather than
      childhood experiences--in predicting adulthood BID.

PMID- 12182268
TI  - Efficacy of moderation-oriented cue exposure for problem drinkers: a randomized
      controlled trial.
AB  - The effectiveness of cue exposure following a priming dose was compared with
      cognitive-behavioral intervention in a community sample of problem drinkers.
      Participants were randomly allocated to 1 of the 2 conditions and received a mean
      of 5.84 (SD = 2.69) sessions. A psychologist blind to treatment condition
      conducted an 8-month follow-up. Compared with pretreatment levels, significant
      decreases in alcohol consumption were evident posttreatment and maintained at
      follow-up for both groups. Reductions in severity of dependence, impaired
      control, and alcohol-related problems were also evident for both groups at follow
      up. No differences in outcome associated with initial severity of alcohol
      dependence were apparent. The results raise the issue of the appropriateness of
      reserving a goal of controlled drinking for those with relatively mild alcohol
      problems and low alcohol dependence.

PMID- 12182269
TI  - Treatment expectancies, patient alliance, and outcome: further analyses from the
      National Institute of Mental Health Treatment of Depression Collaborative
      Research Program.
AB  - Prior analyses from the National Institute of Mental Health Treatment of
      Depression Collaborative Research Program indicated that patients' expectancies
      of treatment effectiveness (S. M. Sotsky et al., 1991) and the quality of the
      therapeutic alliance (J. L. Krupnick et al., 1996) predicted clinical
      improvement. These data were reanalyzed to examine the hypothesis that the link
      between treatment expectancies and outcome would be mediated by patients'
      contribution to the alliance. Among 151 patients who completed treatment, this
      hypothesis was supported, suggesting that patients who expect treatment to be
      effective tend to engage more constructively in session, which helps bring about
      symptom reduction. Therapists' expectancies for patient improvement also
      predicted outcome, although this association was not mediated by the alliance.
      None of the expectancy scales interacted with alliance ratings in the prediction
      of clinical improvement.

PMID- 12182270
TI  - A comparison of cognitive-processing therapy with prolonged exposure and a
      waiting condition for the treatment of chronic posttraumatic stress disorder in
      female rape victims.
AB  - The purpose of this study was to compare cognitive-processing therapy (CPT) with
      prolonged exposure and a minimal attention condition (MA) for the treatment of
      posttraumatic stress disorder (PTSD) and depression. One hundred seventy-one
      female rape victims were randomized into 1 of the 3 conditions, and 121 completed
      treatment. Participants were assessed with the Clinician-Administered PTSD Scale,
      the PTSD Symptom Scale, the Structured Clinical Interview for DSM-IV, the Beck
      Depression Inventory, and the Trauma-Related Guilt Inventory. Independent
      assessments were made at pretreatment, posttreatment, and 3 and 9 months
      posttreatment. Analyses indicated that both treatments were highly efficacious
      and superior to MA. The 2 therapies had similar results except that CPT produced
      better scores on 2 of 4 guilt subscales.

PMID- 12182271
TI  - Pattern of change in prolonged exposure and cognitive-processing therapy for
      female rape victims with posttraumatic stress disorder.
AB  - Curve estimation techniques were used to identify the pattern of therapeutic
      change in female rape victims with posttraumatic stress disorder (PTSD). Within
      session data on the Posttraumatic Stress Disorder Symptom Scale were obtained, in
      alternate therapy sessions, on 171 women. The final sample of treatment
      completers included 54 prolonged exposure (PE) and 54 cognitive-processing
      therapy (CPT) completers. For both PE and CPT, a quadratic function provided the
      best fit for the total PTSD, reexperiencing, and arousal scores. However, a
      difference in the line of best fit was observed for the avoidance symptoms.
      Although a quadratic function still provided a better fit for the PE avoidance, a
      linear function was more parsimonious in explaining the CPT avoidance variance.
      Implications of the findings are discussed.

PMID- 12182272
TI  - Multicenter trial of fluoxetine as an adjunct to behavioral smoking cessation
      treatment.
AB  - The authors evaluated the efficacy of fluoxetine hydrochloride (Prozac; Eli Lilly
      and Company, Indianapolis, IN) as an adjunct to behavioral treatment for smoking
      cessation. Sixteen sites randomized 989 smokers to 3 dose conditions: 10 weeks of
      placebo, 30 mg, or 60 mg fluoxetine per day. Smokers received 9 sessions of
      individualized cognitive-behavioral therapy, and biologically verified 7-day self
      reported abstinence follow-ups were conducted at 1, 3, and 6 months
      posttreatment. Analyses assuming missing data counted as smoking observed no
      treatment difference in outcomes. Pattern-mixture analysis that estimates
      treatment effects in the presence of missing data observed enhanced quit rates
      associated with both the 60-mg and 30-mg doses. Results support a modest, short
      term effect of fluoxetine on smoking cessation and consideration of alternative
      models for handling missing data.

PMID- 12182273
TI  - Alcohol use disorders and cognitive abilities in young adulthood: a prospective
      study.
AB  - The effect of alcohol use disorder (AUD) on cognitive and neuropsychological
      abilities was investigated in a prospective study of 68 freshmen who met past
      year criteria for AUD on 2 or more occasions during their college years and 66
      matched controls. At baseline, participants were administered a total of 14
      subtests from the Wechsler Adult Intelligence Scale-Revised, Wechsler Memory
      Scale, and Halstead-Reitan Neuropsychological Battery. At 7-year follow-up, most
      measures were readministered, along with the Reflective Judgment Interview,
      Watson-Glaser Critical Thinking Appraisal, and Plant Test. Analyses revealed few
      differences between AUD and control groups. However, visuospatial deficits may be
      present among AUD participants with poor baseline visuospatial performance.
      Alcohol exposure measures yielded similar patterns to those shown with AUD.

PMID- 12182274
TI  - Does interpersonal psychotherapy protect women from depression in the face of
      stressful life events?
AB  - The present study compared the role of life events in predicting time to index
      episode onset under conditions of no or variable treatment versus the role of
      life events in predicting time to recurrence during maintenance interpersonal
      psychotherapy (IPT). Eighty-three women with recurrent major depression
      participated in acute IPT treatment followed by 2 years of maintenance IPT. Life
      events were assessed using contextual interview and rating methods. Cox
      regression survival analyses indicated that, although severe life events were
      significantly associated with time to index episode onset, there was little
      evidence of an association between events experienced during maintenance
      treatment and time to recurrence. These results provide evidence that IPT may
      decrease the potency of life events in provoking recurrence.

PMID- 12182275
TI  - Change in emotion-regulation strategy for women with metastatic breast cancer
      following supportive-expressive group therapy.
AB  - Four relatively independent emotion-regulation constructs (suppression of
      negative affect, restraint, repression, and emotional self-efficacy) were tested
      as outcomes in a randomized trial of supportive-expressive group therapy for
      women with metastatic breast cancer. Results indicate that report of suppression
      of negative affect decreased and restraint of aggressive, inconsiderate,
      impulsive, and irresponsible behavior increased in the treatment group as
      compared with controls over 1 year in the group. Groups did not differ over time
      on repression or emotional self-efficacy. This study provides evidence that
      emotion-focused therapy can help women with advanced breast cancer to become more
      expressive without becoming more hostile. Even though these aspects of emotion
      regulation appear trait-like within the control group, significant change was
      observed with treatment.

PMID- 12182276
TI  - Cognitive mediation of rape's mental, physical, and social health impact: tests
      of four models in cross-sectional data.
AB  - Four nested, theoretically specified, increasingly complex models were tested
      representing cognitive mediation of rape's effects on mental, physical, and
      social health. Data were cross-sectional (N = 253 rape survivors). Outcomes were
      standardized assessments of social maladjustment, physical, and psychological
      symptoms, including posttraumatic stress disorder (PTSD). The best-fitting model
      was not fully cognitively mediated. Personological and rape characteristics
      influenced the level of self-blame experienced and the intensity of maladaptive
      beliefs about self and others. Self-blame and maladaptive beliefs predicted
      psychological distress, which strongly influenced all health outcomes. Self
      ratings of rape memory characteristics contributed little to predicting postrape
      distress. The model accounted for 56% of the variance in general distress,
      including 91% of psychological symptom severity; 54% of PTSD symptoms; 65% of
      social maladjustment; and 17% of physical symptoms. Longitudinal replication is
      planned.

PMID- 12182277
TI  - The mediating roles of perceived social support and resources in the self
      efficacy-suicide attempts relation among African American abused women.
AB  - The authors examined whether self-efficacy among African American abused women
      decreased their risk of suicide attempts through the mediating influences of
      perceived social support from friends, perceived social support from family, and
      perceived effectiveness for obtaining material resources. The sample consisted of
      100 women who presented to a hospital following a suicide attempt and 100 women
      who presented to the same hospital for nonemergency medical problems. Results
      revealed that the association between self-efficacy and suicide attempt status
      was partially accounted for by the mediating roles of perceived social support
      from friends and family, and perceived effectiveness at obtaining resources.
      Findings suggest that interventions to increase abused women's self-efficacy
      should focus on increasing their capacity to obtain social and material
      resources.

PMID- 12182279
TI  - Screening for posttraumatic stress disorder in a general psychiatric outpatient
      setting.
AB  - Posttraumatic stress disorder (PTSD) may affect survivors of a number of
      accidents and illnesses, in addition to violence victims and combat veterans.
      Prior research suggests that PTSD may be underdiagnosed when trauma is not the
      presenting problem. Thus, a PTSD screening scale might have utility in routine
      clinical settings. The authors evaluated the screening performance of the
      Posttraumatic Diagnostic Scale (PDS) in a general psychiatric setting. Results
      indicated that the PDS performed as well in this setting as it did in the
      original trauma-focused validation studies, independent of PTSD status as a
      primary, versus secondary, reason for presenting. A simple cutoff score was
      adequate for case identification. There were no gender effects, and the scale
      performed equally well among patients with, versus without, a depressive
      diagnosis.

PMID- 12182278
TI  - Effects and generalizability of communally oriented HIV-AIDS prevention versus
      general health promotion groups for single, inner-city women in urban clinics.
AB  - A primary prevention, behavioral intervention designed to reduce HIV risk
      behavior was tested in a randomized, controlled trial with single, inner-city
      women. A total of 935 women were randomly assigned to 1 of 3 conditions: a small
      group, 6-session communally oriented HIV prevention intervention; a yoked general
      health promotion intervention control; or a standard care control. Both
      interventions involved the interactive use of videotapes by live group leaders.
      The HIV prevention intervention, in particular, resulted in significant positive
      effects on self-reported and behaviorally assessed safer-sex behavior. Women in
      the HIV prevention group showed reduced point prevalences of medically tested
      sexually transmitted diseases at follow-up in some comparisons.

PMID- 12182280
TI  - Gay-related stress and emotional distress among gay, lesbian, and bisexual
      youths: a longitudinal examination.
AB  - The longitudinal relations between gay-related stress (i.e., gay-related
      stressful events, negative attitudes toward homosexuality, and discomfort with
      homosexuality) and emotional distress (i.e., anxious symptoms, depressive
      symptoms, and conduct problems) were examined at 3 assessment periods (baseline,
      6 months, and 12 months) among 140 gay, lesbian, and bisexual (GLB) youths.
      Although some findings were consistent with the hypothesis that stress would be
      associated with subsequent distress among GLB youths, the larger number of
      nonsignificant relations and the presence of relations between distress and
      subsequent gay-related stress indicate that the hypothesis was unsupported. The
      authors discuss the potential reasons for the lack of hypothesized relations and
      offer suggestions for future research.

PMID- 12182281
TI  - A finite mixture model of growth trajectories of adolescent alcohol use:
      predictors and consequences.
AB  - The current study sought to identify classes of growth trajectories of adolescent
      alcohol use and to examine the predictors and outcomes associated with the
      classes. Alcohol use was assessed from Grades 7 to 12 in a school-based sample.
      Latent growth mixture modeling was used, and results indicated 5 discrete
      longitudinal drinking patterns. The 2 most common drinking patterns included
      occasional very light drinking from Grades 7 to 12 and moderate escalation in
      both quantity and frequency of alcohol use. One group drank infrequently but at
      high levels throughout the study period. Another group exhibited rapid escalation
      in both quantity and frequency. The final group started at high levels of
      frequency and quantity in Grade 7 and showed rapid de-escalation in frequency.
      Emotional distress and risk taking distinguished the classes, and all classes,
      particularly rapid escalators, showed elevated levels of alcohol-related problems
      relative to occasional very light drinkers.

PMID- 12182282
TI  - The role of self-control in early escalation of substance use: a time-varying
      analysis.
AB  - This research tested predictions about the role of temperament and self-control
      in early substance use (tobacco, alcohol, and marijuana). A sample of 1,526
      participants was assessed in 6th grade (mean age = 11.5 years) and followed with
      yearly assessments through 9th grade. Latent growth models showed temperament
      dimensions were related to early substance use, and their effects were mediated
      through generalized self-control ability. Time-varying effects indicated rate of
      growth in substance use was higher among participants who showed increases in
      poor self-control and lower among participants who showed increases in good self
      control. Results in self-report data were corroborated by independent teacher
      ratings. Findings are discussed with reference to epigenetic models of protection
      and vulnerability.

PMID- 12182283
TI  - Differentiating stages of smoking intensity among adolescents: stage-specific
      psychological and social influences.
AB  - Researchers' understanding of the impact of sociocultural and psychological
      factors on the various stages of adolescent smoking uptake is limited. Using
      national data, the authors examined transitions across smoking stages among
      adolescents (N = 20,747) as a function of interpersonal, familial, and peer
      domains. Peer smoking was particularly influential on differentiating regular
      smoking, whereas alcohol use was most influential on earlier smoking. Although
      significant, depression and delinquency were attenuated in the context of other
      variables. Higher school grade was more likely to differentiate regular smoking
      from earlier smoking stages, whereas African American ethnicity and connectedness
      to school and family were protective of smoking initiation. Results lend support
      for an interactional approach to adolescent smoking, with implications for stage
      matched prevention and intervention applications.

PMID- 12182284
TI  - The new medical group: managing patient health care to include quality and
      affordability.

PMID- 12182285
TI  - New partnerships in cancer programs.

PMID- 12182286
TI  - Assisting nurses and health care professionals in educating patients facing
      unrelated stem cell transplants.

PMID- 12182287
TI  - Radiopharmaceutical therapy.

PMID- 12182288
TI  - The team concept revisited.

PMID- 12182289
TI  - Influence of the microgap in the peri-implant hard and soft tissues: a
      histomorphometric study in dogs.
AB  - PURPOSE: The purpose of this study was to examine the dimensions and
      relationships of the peri-implant tissues surrounding osseointegrated 2-stage
      implants placed at different depths in bone. MATERIALS AND METHODS: Twenty-four
      implants were placed in the mandibles of 4 mongrel dogs. A modification of the
      surgical protocol was introduced so that in group I, implants remained 1 mm above
      the bone crest, in group II, implants were placed level with the bone crest; and
      group III implants were countersunk to approximately 1 mm below the bone crest.
      After 3 months, abutment operations were carried out with the placement of 3-mm
      standard abutments. Following a healing period of 3 months the dogs were
      sacrificed. A total of 20 implants were available for histometric analysis. Non
      decalcified sections were evaluated for the dimensions of the junctional
      epithelium, connective tissue band, marginal bone level, and bone-to-metal
      contact. RESULTS: Histologic observations showed a mucosal barrier consisting of
      keratinized oral epithelium continuous with a thin junctional epithelium facing
      the implant and abutment surface. Junctional epithelium showed a mean of 1.67 mm
      for group 1, 1.93 mm for group II, and 2.78 mm for group III. These values were
      not statistically different. The band of connective tissue had a mean of 1.13 mm
      for group 1, 0.92 mm for group II, and 1.60 mm for group III. These values were
      not statistically different, except for group II versus group III. Bone level had
      a mean of 2.50 mm for group 1, 2.30 mm for group II, and 1.60 mm for group III.
      These differences were significant between groups I and III. The surface of bone
      contact along the implant (BMC%) showed mean values of 46.8% in group 1, 53.7% in
      group II, and 49.0% in group III (no significant differences among the 3 groups).
      DISCUSSION: There was a clear tendency of the epithelium and connective tissue to
      be longer the deeper the implants were placed, although those differences were
      not statistically significant. Bone loss was smaller for group III (countersink
      group). This is not in accordance with recent articles which have stated that
      bone will maintain its biologic width. CONCLUSIONS: When the microgap between
      implants and abutments was placed deeper in the bone, additional bone loss did
      not result.

PMID- 12182290
TI  - Prospective evaluation of implants connected to teeth.
AB  - PURPOSE: This prospective clinical trial examined the effect on teeth and
      implants when rigidly or non-rigidly connected in a cross-arch model. MATERIALS
      AND METHODS: Thirty patients received 2 implants, 1 on each side of the mandible,
      and were restored with 3-unit fixed partial dentures connected either rigidly or
      non-rigidly to an abutment tooth. Patients were followed for at least 5 years
      post-restoration. RESULTS: Repeated-measures analysis revealed no significant
      difference in crestal bone loss at implants (rigid versus non-rigid methods). An
      overall significant difference (P < .001) was found comparing methods for teeth.
      Paired t tests revealed no significant differences in crestal bone levels for
      implants or teeth at the 5-year recall. Kaplan-Meier methods and the Cox
      proportional hazards model showed no differences between attachment methods with
      regard to success based on survival and bone loss criteria. During the 5-year
      recall period, 1 implant (rigid side) was removed. Four implants developed bone
      loss greater than 2 mm during the course of this trial. One tooth on the rigid
      side and 2 teeth on the non-rigid side had greater than 2 mm of crestal bone loss
      and were removed secondary to fractures. In all, 5 abutment teeth were removed,
      all of which had been treated with root canal therapy and fractured at the
      interface of the post within the tooth. There was no clear relationship of tooth
      fracture to attachment. Repeated-measures analysis of mobility values revealed no
      significant changes over the time course of this study, and paired t tests
      revealed no statistically significant differences between implants for mobility.
      Repeated-measures analysis and paired t tests for probing depth revealed no
      significant changes over the time course of this study. There were no significant
      differences in soft tissue indices for either attachment method. The percentage
      of patients who had measurable intrusion was 66% for the non-rigid group, and 44%
      for the rigid group; 25% of the non-rigid teeth had greater than 0.5 mm
      intrusion, compared with 12.5% for the rigid group. For the 2 time periods
      evaluated, there was no significant increase in intrusion over time. The non
      rigid-side implant required more nonscheduled visits to treat problems than the
      rigid implant and the teeth. DISCUSSION: Most patients were treated successfully
      with rigid or non-rigid attachment of implants to teeth. CONCLUSION: The high
      incidence of intrusion and non-scheduled patient visits suggest that alternative
      treatments without connecting implants to teeth may be indicated.

PMID- 12182291
TI  - Autogenous demineralized dentin matrix for tissue engineering applications:
      radiographic and histomorphometric studies.
AB  - PURPOSE: This work evaluated the osteoconductive properties of autogenous
      demineralized dentin matrix (ADDM) on surgical bone defects in the parietal bone
      of rabbits, using the guided bone regeneration technique and
      polytetrafluoroethylene (PTFE) membrane. MATERIALS AND METHODS: Surgical bone
      defects were created in 24 adult rabbits and repaired with either ADDM and PTFE
      (experimental group) or PTFE alone (control group). The ADDM had been obtained
      from the central incisors of the experimental rabbits. The rabbits were
      sacrificed after 15, 30, 60, and 90 days and the defects examined
      radiographically and histologically. RESULTS: Radiographically, the defects in
      the experimental animals achieved radiopacity more quickly than the defects in
      the control group. DISCUSSION: After 15, 30, 60, and 90 days of observation
      following surgery, the ADDM slices appeared to stimulate new bone formation. The
      dentin slices were completely incorporated into the new bone tissue and were
      resorbed during the bone repair. CONCLUSIONS: Bone repair was accelerated on the
      bone defects treated with ADDM when compared to the control group.

PMID- 12182292
TI  - Influence of particle size of autogenous bone grafts on the early stages of bone
      regeneration: a histologic and stereologic study in rabbit calvarium.
AB  - PURPOSE: The aim of this study was to investigate the influence of particle size
      of autogenous bone grafts on the early stages of bone regeneration. MATERIALS AND
      METHODS: Bicortical skull bone defects were prepared in 15 rabbits (4 in each
      rabbit). Two defects were filled at random with either small (0.5 to 2 mm3) or
      large (10 mm3) autogenous bone particles. In addition, 1 defect was left unfilled
      (control defect). All defects were covered bicortically by expanded
      polytetrafluoroethylene membranes. The animals were divided randomly into 3
      groups and sacrificed after 1, 2, and 4 weeks, respectively. Histologic and
      stereologic evaluations were performed after the sections were blinded. RESULTS:
      No significant differences in total vessel surface area could be identified among
      the 3 groups. The total volume of newly formed bone in defects with small
      particles was larger and more mature compared to defects with large particles
      after 2 and 4 weeks. Furthermore, the resorption of small particles was more
      pronounced after 4 weeks, documenting a higher level of bone substitution
      compared to large particles. DISCUSSION: The early stages of bone regeneration
      were influenced by the particle site of autogenous bone grafts. CONCLUSION: The
      present study indicated that particles of 0.5 to 2 mm3 in size should be
      preferred to particles of 10 mm3 in size for bone grafting.

PMID- 12182293
TI  - Microscopic analysis of reconstructed maxillary alveolar ridges using autogenous
      bone grafts from the chin and iliac crest.
AB  - PURPOSE: The aim of this study was to histologically analyze the bone repair of
      maxillary areas reconstructed with autogenous bone grafts using 2 different donor
      sites, the ilium and the chin. MATERIALS AND METHODS: Specimens were retrieved
      with trephine burs positioned transversely in augmented ridges 4 months after
      placement of the grafts. To analyze bone conditions, a histomorphometric study of
      ground sections was performed using a special template to identify 3 specific
      regions of the specimens: cortical bone, cancellous bone, and the region of
      transition between the alveolar ridge and the graft. Ten patients, 5 men and 5
      women, with a mean age of 47 years (range 28 to 67) were evaluated. RESULTS:
      Results indicated good incorporation of the grafts in this period, demonstrated
      by intense osteogenesis indicating an active remodeling process. DISCUSSION: In
      both groups, the improvement in bone quality of the receptor site was evident,
      independent of the size of the reconstruction, although chin grafts presented
      better bone quality. CONCLUSIONS: From this study it was possible to conclude
      that a period of 4 months is sufficient for the placement of osseointegrated
      implants in reconstructed areas, where chin or iliac autogenous grafts have been
      used.

PMID- 12182294
TI  - Immediate mandibular rehabilitation with endosseous implants: simultaneous
      extraction, implant placement, and loading.
AB  - PURPOSE: This report of a clinical patient series indicates the relative safety
      and illustrates the procedures involved in the extraction of remaining teeth
      followed by immediate implant placement and loading with a simple acrylic resin
      fixed denture. MATERIALS AND METHODS: Ten consecutive patients who selected tooth
      extraction and implant-supported fixed denture rehabilitation of the mandible
      were treated using a 1-visit approach for extraction, implant placement, and
      restoration. Healthy individuals (10 women) were treated under local anesthesia.
      Fifty-four implants were placed in 10 patients. Five or 6 Astra Tech implants (11
      or 13 mm long) were placed into the edentulous parasymphyseal region of the
      mandible. Four to 6 implants (48 of 54) were immediately loaded by the
      fabrication of a simple acrylic resin fixed denture. The criterion for loading
      was clinical judgment of primary stability, ie, the absence of axial or lateral
      mobility with physical resistance to rotation. Patients were recalled at 1, 3,
      and 12 weeks. At 12 weeks, impressions were made for the fabrication of a screw
      retained fixed denture. The fixed dentures were completed using conventional
      fabrication and prosthetic techniques. RESULTS: After a period of 6 to 18 months,
      all 54 implants had survived and were considered 100% successful by independent
      testing of mobility and radiographic evidence of osseointegration. There were no
      surgical complications. Fracture and debonding of the acrylic resin provisional
      denture occurred for 1 patient during the first 12 weeks of treatment.
      DISCUSSION: Advantages to extraction with simultaneous replacement include the
      maintenance of vertical dimension, elimination of reline procedures and interim
      denture therapy, and potential improvement of soft tissue healing. CONCLUSION:
      This therapeutic approach simplifies patient care without apparent additional
      risk.

PMID- 12182295
TI  - Maximum dislodging forces of implant overdenture stud attachments.
AB  - PURPOSE: The aim of this study was to compare the retention and stability of the
      Nobel Biocare standard ball (NBS), Nobel Biocare 2.25-mm-diameter ball (NB2),
      Zest Anchor (ZA), Zest Anchor Advanced Generation (ZAAG), Sterngold ERA orange
      (SEO), and Sterngold ERA white (SEW) attachments on an implant-retained
      overdenture model. MATERIALS AND METHODS: The attachments were tested using 2
      permanently placed Branemark System implants on a test model that was attached to
      an Instron machine (crosshead speed 50.8 mm/minute). Each attachment had one part
      embedded in a denture-like housing and the other part screwed into the implants.
      Dislodging tensile forces were applied to the housings in 3 directions simulating
      function: vertical, oblique, and anterior-posterior. Eight tests were done in 3
      directions with 6 samples of each attachment. The dislodging forces generated
      measurements of the peak load (maximum dislodging force). A 1-way analysis of
      variance followed by the Tukey studentized range test was used to determine
      groups that were significantly different. All tests for significance were carried
      out at the .05 level of significance. RESULTS: Results showed the ZAAG attachment
      to be the most retentive for the peak load measurement when subjected to
      vertically directed forces, with mean values and standard deviations of 37.2 +/-
      5.5 N. The next most retentive attachment was the NBS, followed by the SEO, NB2,
      SEW, and ZA. For obliquely directed forces, the ZAAG attachment was the most
      retentive, with mean values and standard deviations of 27.2 +/- 4.2 N. The next
      most retentive was the NBS, followed by the NB2, SEO, ZA, and SEW. For anterior
      posteriorly directed forces, results showed the NBS had the highest measured
      retentive force, with mean values and standard deviations of 34.6 +/- 18.8 N, but
      this was not statistically different from the NB2 and ZAAG; this was followed by
      the SEO, SEW, and ZA. DISCUSSION: There has been a marked resurgence in the
      treatment of patients with overdentures using implant attachments as retentive
      devices. The maximum force developed (a measure of retention) as the implant stud
      attachments were resisting removal from the implant abutments was determined.
      CONCLUSIONS: Based on the present study, the clinician may be able to make
      empirical decisions on attachment selection, depending on the amount of retention
      desired and the specific clinical situation.

PMID- 12182296
TI  - Comparison of uniaxial resistance forces of cements used with implant-supported
      crowns.
AB  - PURPOSE: Provisional cements are commonly used to facilitate retrievability of
      cement-retained fixed implant restorations. While the functional life spans of
      these cements are unpredictable, the relative retentiveness of various permanent
      and provisional cements between dental alloys and titanium abutments is not well
      documented. The aim of this study was to compare the uniaxial resistance forces
      of permanent and provisional luting cements used for implant-supported crowns.
      MATERIALS AND METHODS: Seven samples on 4 different abutments (a total of 28
      crowns) were cast using a gold-platinum-palladium alloy. The crowns were cemented
      with 3 different provisional, polycarboxylate, and glass-ionomer cements and 1
      zinc phosphate cement. After storage of samples in artificial saliva for 24
      hours, tensile tests were performed. RESULTS: While the highest uniaxial
      resistance forces were recorded for polycarboxylate cements, provisional cements
      exhibited significantly lower failure strengths (P < .05). The uniaxial
      resistance force of cements on different abutments exhibited notably different
      trends; however, more force was required to remove crowns cemented to long
      abutments (P < .05). DISCUSSION: Glass-ionomer and zinc phosphate cements may be
      used to increase the maintenance of implant-supported crowns. Temporary
      cementation of such restorations may necessitate frequent recementation,
      particularly for restorations on short abutments. CONCLUSIONS: Temporary
      cementation may be more suitable for restorations supported by multiple implants.

PMID- 12182297
TI  - Evaluation of a predoctoral implant curriculum: does such a program influence
      graduates' practice patterns?
AB  - PURPOSE: Didactic predoctoral dental implant education is part of the curriculum
      in most US dental schools. However, fewer than half offer laboratory instruction,
      and only a few allow dental students to place and restore dental implants. The
      additional time necessary for laboratory and clinical experience encroaches on an
      already crowded curriculum. Is the additional time necessary in the curriculum
      for laboratory and clinical experience by dental students reflected by the
      practice patterns of graduates who have completed such a program over the past 10
      years? MATERIALS AND METHODS: A survey was designed to determine the implant
      practice patterns of graduates of the Creighton School of Dentistry, Omaha,
      Nebraska, for the 10-year period 1988 to 1997. These graduates had all
      participated in a formal undergraduate didactic and laboratory curriculum in
      implant dentistry. Approximately half also had the opportunity to place and/or
      restore dental implants while students. The survey was also sent to graduates
      (also 1988 to 1997) from a midwestern dental school without a formal laboratory
      or clinical component (used as a control group). The data were analyzed
      statistically. RESULTS: In comparison to the control group (56% versus 23%), more
      than twice as many Creighton graduates restore dental implants as a part of their
      general practice, surgically place more dental implants, refer more implant
      patients to surgical specialists, and seek more continuing education hours
      related to implant dentistry. These conclusions were all supported by statistical
      analysis of the data. DISCUSSION: Student clinical experience with implant
      dentistry appears to significantly increase the incorporation of implant
      dentistry into future dental practices. Even if clinical experience was not an
      option, a school curriculum which included both didactic and laboratory
      participation still significantly increased the number of graduates who included
      implant dentistry in their practices. CONCLUSION: The inclusion of laboratory and
      clinical experience in implant dentistry in the CUSD undergraduate curriculum
      resulted in significantly greater participation in implant dentistry at the
      general practice level.

PMID- 12182298
TI  - Multicenter retrospective analysis of the solid-screw ITI implant for posterior
      single-tooth replacements.
AB  - PURPOSE: This report involves the retrospective analysis of ITI implants placed
      and/or restored by a group of 7 clinicians located throughout the United States
      (5 periodontists and 2 prosthodontists). MATERIALS AND METHODS: Six hundred
      seventy-five posterior single-tooth implants were restored in 471 patients
      (average time of loading 21.30 months, with a range of 1 to 78 months). Three
      hundred seventy implants and 71 implants were placed in mandibular and maxillary
      molar sites, respectively, and 108 and 126 were placed in mandibular and
      maxillary premolar sites, respectively. RESULTS: A cumulative survival rate of
      99.1% was obtained for all sites (6 failures). The survival rates for individual
      sites were as follows: 98.4% mandibular molars, 100% maxillary molars, 100%
      mandibular premolars, and 100% maxillary premolars. "At-risk" implants (1 to 2 mm
      of radiographic bone loss) were noted at 5 sites. DISCUSSION: Minimal restorative
      problems were found with either screw-retained (n = 71) or cemented restorations
      on solid abutments (n = 600); 80.3% of screw-retained and 98.2% of cemented
      restorations were free of complications, respectively. Patient satisfaction
      scores were high (97.4%) as determined by the Patient Satisfaction Questionnaire.
      CONCLUSION: The data suggest that solid-screw (4.1 or 4.8 mm wide) ITI implants
      can be a satisfactory choice for posterior single-tooth restorations.

PMID- 12182299
TI  - The endoscopically controlled osteotome sinus floor elevation: a preliminary
      prospective study.
AB  - PURPOSE: It was the aim of the present prospective study to quantify the gain in
      height of implant sites by endoscopically controlled osteotome sinus floor
      elevations (ECOSFE) with simultaneous implant placement and to report the number
      of sinus membrane perforations. MATERIALS AND METHODS: From October 1999 to
      December 2000, of 92 sinus floor elevations, 18 were carried out endoscopically
      controlled with an osteotome technique. As augmentation material, beta-tricalcium
      phosphate (beta-TCP) or autogenous bone was used; 22 implants were placed.
      RESULTS: The residual height of the alveolar crest in the posterior maxilla was
      6.8 +/- 1.6 mm on average. The implant lengths ranged from 10 to 16 mm (mean
      implant length 12.2 +/- 1.4 mm). They were significantly larger than the residual
      height of the alveolar crests (P < .0005). Elevation of the sinus floor with an
      osteotome had to be supported by conventional sinus floor elevation instruments
      after a mean elevation of 3.0 +/- 0.8 mm to prevent perforation of the sinus
      membrane. However, 1 perforation occurred, which was repaired with a periosteal
      patch. At stage 2 surgery, 2 implants were removed because of mobility.
      Endoscopic control revealed one case in which beta-TCP could be found within the
      sinus; another case showed areas of polypoid mucosa on the sinus floor.
      DISCUSSION: With the ECOSFE, perforations of the sinus membrane can be
      visualized; however, they cannot be avoided. Although this technique is less
      invasive than the lateral window technique, it cannot be recommended as a
      standard procedure in the posterior maxilla because of the large amount of
      additional equipment needed and the technically demanding procedure. CONCLUSION:
      The use of the ECOSFE should be confined to scientific trials.

PMID- 12182300
TI  - Effects of immediate loading with threaded hydroxyapatite-coated root-form
      implants on single premolar replacements: a preliminary report.
AB  - PURPOSE: This prospective study evaluated the immediate loading of single,
      threaded, root-form implants placed in the maxillary premolar area. MATERIALS AND
      METHODS: Ten human subjects were included in this preliminary report. In all
      cases, a screw-retained temporary acrylic resin crown was placed immediately
      after implant surgery. The definitive screw-retained metal-ceramic crown was
      placed 6 months later. RESULTS: Standardized radiographs demonstrated 0.58, 0.73,
      0.84, and 0.90 mm mean marginal bone loss at 1, 3, 6, and 12 months after implant
      surgery, respectively. Implant mobility was evaluated with the Periotest device.
      At the day of surgery, mean mobility was -3.3, while minor changes were observed
      thereafter: mean values of -3.77, -3.47, and -3.63 were recorded at 3, 6, and 12
      months after implant surgery, respectively. Sulcus depth appeared relatively
      stable after the 3rd month when the implant platform was used as a reference.
      Recession of 0.43 mm was recorded between the 3rd and 12th month; when the depth
      of the peri-implant sulcus was measured from the implant platform, 0.1 mm of
      change was seen between the 3rd and 12th month. Probing depth measurements
      revealed that 3 months after implant placement, average probing depth was 3.60
      mm, while at 12 months it was 3.20 mm. DISCUSSION: The peri-implant soft tissue
      parameters (bleeding on probing, probing depth, peri-implant soft tissue level),
      mobility, and marginal bone level appeared to be similar to findings of previous
      studies regarding the conventional 2-stage loading protocol. CONCLUSION: Results
      of the current study provided evidence that, under the condition of this
      investigation, single root-form implants can be immediately loaded when placed in
      the maxillary premolar area.

PMID- 12182301
TI  - Rehabilitation of patients with congenital unrepaired cleft palate defects using
      free iliac crest bone grafts and dental implants.
AB  - PURPOSE: To rehabilitate the mastication and speech of edentulous congenital
      cleft lip and palate patients with the use of endosseous implants in conjunction
      with bone augmentation. MATERIALS AND METHODS: Between 1992 and 1999, 6 partially
      and 4 completely edentulous adult patients with complex cleft palate defects were
      treated. Six patients had large, unrepaired defects of the hard and soft palate,
      whereas the other 4 had residual oronasal fistulas after failed palatoplasty and
      bone grafting. In 8 patients, free inlay-antral and simultaneous lateral-onlay
      bone grafts (3 patients) were obtained from the iliac crest, and dental implants
      were placed secondarily. In the other 2 patients, the implants were placed
      without grafting in recent extraction sites. Rigid bars with extensions over the
      defects were used to support obturator prostheses (n = 7), or patients were
      provided with fixed implant-supported prostheses (n = 3). In all, 50 cylindric,
      screw-type dental implants were placed and followed up for 1 to 8 years (mean, 5
      years). RESULTS: Six implants were regarded as early failures and 1 was lost
      during the first year of loading; 1 patient lost all 5 implants. The cumulative
      success rate at 5 years was 85.7%. DISCUSSION AND CONCLUSION: All 9 successfully
      rehabilitated patients reported a remarkable functional and psychologic
      improvement after the treatment. The described treatment protocol also seemed to
      be effective for correcting velopharyngeal insufficiency in patients using an
      obturator prosthesis.

PMID- 12182302
TI  - Bone response to plasma-sprayed hydroxyapatite and radiofrequency-sputtered
      calcium phosphate implants in vivo.
AB  - PURPOSE: The objective of this study was to evaluate the effect of radiofrequency
      (RF) sputtered calcium phosphate (CaP) coating of titanium implants on bond
      strength at the bone-implant interface and percent bone contact length. MATERIALS
      AND METHODS: Cylindric sputtered CaP-coated and plasma-sprayed hydroxyapatite-
      (HA) coated implants (4.0 mm diameter and 8 mm length) were implanted in dog
      mandibles. Half the sputtered CaP-coated implants were heat-treated. RESULTS:
      Twelve weeks after implant placement, no statistical differences in the mean
      ultimate interfacial strengths were observed between as-sputtered CaP-coated,
      sputtered CaP-coated heat-treated, and control plasma-sprayed HA-coated implants.
      Histomorphometric evaluation indicated that the percent bone contact lengths for
      the plasma-sprayed HA-coated implants and the as-sputtered CaP-coated implants
      were similar and significantly greater than that for the sputtered CaP-coated
      heat-treated implants. Differences in the ultimate interfacial strength and
      percent bone contact length between different implant sites in the mandible were
      not observed. DISCUSSION: The results of this study, considered together with the
      results of previous studies, suggest that once early osseointegration is
      achieved, biodegradation of the thin CaP coatings is not detrimental to bone
      coating-implant fixation, and does not compromise bone responses to the coated
      implant surfaces. CONCLUSION: The interfacial strength and histomorphometric data
      suggest that the CaP coatings applied using the sputtering process produce bone
      responses similar to those of HA coatings applied using plasma spraying.

PMID- 12182303
TI  - Immediate placement and implant loading for expedited patient care: a patient
      report.
AB  - This patient report concerns etiologic factors leading to a failed natural
      dentition, masticatory function, and poor dental esthetics in a 30-year-old
      woman. The surgical and restorative treatment provided for the patient was
      designed to address her dental phobia, location of residence, and debilitated
      oral condition. While the following case report details an example of the
      clinical success that can be achieved through advances in dental implant
      treatment, the most satisfying event was not necessarily the procedure itself,
      but the profound change that the generosity of the osseointegration community has
      made on the life of a needy individual. Through the active leadership of the
      Osseointegration Foundation Charitable Grant Program, the patient, whose complex
      treatment is described here, was able to take advantage of treatment that
      otherwise would not have been available to her. This complex treatment was
      enabled by the Osseointegration Foundation and other caring donors.

PMID- 12182304
TI  - The McGill consensus statement on overdentures. Mandibular two-implant
      overdentures as first choice standard of care for edentulous patients. Montreal,
      Quebec, May 24-25, 2002.

PMID- 12182305
TI  - Fibroblast adhesion and proliferation on poly(ethylene glycol) hydrogels
      crosslinked by hydrolyzable polyrotaxane.
AB  - Fibroblast culture was performed to evaluate cell adhesion and proliferation on
      poly(ethylene glycol) (PEG) hydrogels crosslinked by a hydrolyzable polyrotaxane.
      The polyrotaxane consisting of alpha-cyclodextrins (alpha-CDs) and PEG terminated
      by benzyloxycarbonyl (Z)-L-phenylalanine (L-Phe) via ester linkage was used as a
      multi-functional crosslinker in the PEG hydrogels. From the results of contact
      angle and small angle light scattering measurements, it was suggested that the
      surface and bulk structure of the PEG hydrogels were heterogeneous. Fibroblast
      adhesion and proliferation on the hydrogels was observed. The number of
      fibroblast adhesion on the hydrogels crosslinked by the polyrotaxane was
      proportional to contact angle values and correlation length, and was
      significantly higher than those crosslinked by alpha-CDs in spite of similar
      contact angle and correlation length. These findings suggest that the cells
      recognize the surface heterogeneity due to the polyrotaxane structure, and the
      number of cell adhesion and proliferation is controllable by the polyrotaxane
      content in feed.

PMID- 12182306
TI  - Study on the three-dimensional proliferation of rabbit articular cartilage
      derived chondrocytes on polyhydroxyalkanoate scaffolds.
AB  - Polymer scaffold systems consisting of poly(hydroxybutyrate-co-hydroxyhexanoate)
      (PHBHHx)/polyhydroxybutyrate (PHB) (PHBHHx/PHB) were investigated for possible
      application as a matrix for the three-dimensional growth of chondrocyte culture.
      Blend polymers of PHBHHx/PHB were fabricated into three-dimensional porous
      scaffolds by the salt-leaching method. Chondrocytes isolated from rabbit
      articular cartilage (RAC) were seeded on the scaffolds and incubated over 28
      days, with change of the culture medium every 4 days. PHB scaffold was taken as a
      control. Methylthiazol tetrazolium (MTT) (3-[4,5-dimethylthiazol-2-yl]-2,5
      diphenyltertra-zolium bromide) assay was used to quantitatively examine the
      proliferation of chondrocytes. Results showed that chondrocytes proliferated
      better on the PHBHHx/PHB scaffolds than on PHB one. The maximal cell densities
      were all observed after 7 days of incubation. As for the blend polymers, cells
      grew better on scaffolds consisting of PHBHHx/PHB in ratios of 2:1 and 1:2 than
      they did on PHBHHx/PHB of 1:1. Scanning electron microscopy (SEM) also showed
      that large quantities of chondrocytes grew initially on the surface of the
      scaffold. After 7 days, they further grew into the open pores of the blend
      polymer scaffolds. Morphologically, cells found on the surface of the scaffold
      exhibited a flat appearance and slowly form confluent cell multilayers starting
      from 14 to 28 days of the growth. In contrast, cells showed rounded morphology,
      formed aggregates and islets inside the scaffolds. In addition, chondrocytes
      proliferated on the scaffold and preserved their phenotype for up to 28 days.

PMID- 12182307
TI  - Polymerization kinetics of HEMA/DEGDMA: using changes in initiation and chain
      transfer rates to explore the effects of chain-length-dependent termination.
AB  - The effect of kinetic chain length and chain transfer on the polymerization
      kinetics and network structure in polymerizations of loosely crosslinked 2
      hydroxyethyl methacrylate/di(ethylene glycol) dimethacrylate mixtures was
      explored. Polymerization behavior of the monomer mixture in the presence and
      absence of a chain transfer agent was monitored at various initiation rates and
      chain transfer agent concentration levels. Dependence of the polymerization rate
      on the initiation rate was found to deviate from the classical square-root
      relationship because of chain-length-dependent termination. This effect was
      further confirmed by addition of a chain transfer agent. The presence of a chain
      transfer agent led to the formation of shorter kinetic chains, which enhanced
      termination and slowed the polymerization. Investigation of the polymerization
      kinetics after cessation of irradiation yielded kt/kp[M] values for both systems.
      Prior to the onset of reaction diffusion-controlled termination, the system that
      included a chain transfer agent exhibited much higher kt/kp[M] values than the
      polymerization system without added chain transfer agent. In addition, the onset
      of reaction diffusion-controlled termination was delayed to higher conversions in
      the system containing chain transfer agent. The impact of a chain transfer agent
      on the polymerization behavior and kinetics demonstrates that the chain-length
      dependent termination phenomenon is indeed important and must be considered in
      kinetic modeling of loosely crosslinked systems.

PMID- 12182308
TI  - Plasma sprayed wollastonite/TiO2 composite coatings on titanium alloys.
AB  - Wollastonite/TiO2 composite coatings were prepared using plasma spraying
      technology onto Ti-6Al-4V substrate. The composite coatings exhibit obvious
      lamellar structure with alternating wollastonite coating and TiO2 coating. No
      obvious cracks exist on the interface between coatings and substrate. In the case
      of composite coatings, the primarily crystalline phases of the coatings are
      wollastonite and rutile, indicating wollastonite and TiO2 did not react during
      plasma spraying process. Some of rutile in the powders transforms into anatase
      due to plasma spraying. The mean bond strength of the composite coatings is
      higher than 30 MPa. The Vickers microhardness of coatings increase with the
      increase in the content of TiO2. Wollastonite/TiO2 composite coatings were soaked
      in simulated body fluid to examine their bioactivity. Carbonate-containing
      hydroxyapatite (CHA) layer was formed on the surface of the wollastonite and W7T3
      coatings soaked in simulated body fluid, while was not formed on the surface of
      the TiO2 and W3T7 coatings after immersion. In addition, a rich-silica layer
      appeared at the interface of CHA and wollastonite and W7T3 coatings. In order to
      investigate the cytocompatibility of the coatings, osteoblast was seeded onto the
      surface of the coatings. The scanning electron microscopy observation showed that
      the addition of wollastonite promote the proliferation of osteoblast. It is
      enough to prove that the wollastonite and wollastonite/TiO2 composite coatings
      possess excellent cytocompatibility.

PMID- 12182309
TI  - Healing of alveolar bone in resorbable and non-resorbable membrane-protected
      defects. A histologic pilot study in dogs.
AB  - Two main types of membrane barriers are used for bone regeneration, non
      resorbable and resorbable. Polytetrafluorethilene non-resorbable membranes have
      been extensively studied but they require a second surgical step for removal.
      Although polylactic acid (PLA) resorbable membranes avoid this problem, they have
      not been sufficiently evaluated on bone defects. The purpose of this pilot study
      was to compare the healing events of bone regeneration after placement of non
      resorbable or resorbable membranes and to evaluate the amount of newly formed
      bone 2 and 4 months after membrane placement. Mandibular second, third and fourth
      premolars of four adult mongrel dogs were extracted bilaterally. Two rectangular
      bone defects (8 mm corono-apical and 12 mm mesial-distal) were created
      bilaterally 3 months after tooth extractions. Each dog received two resorbable
      membranes and one non-resorbable membrane; one defect was left untreated. Two
      dogs were killed at 2 months and the remaining two at 4 months following surgery.
      Undecalcified sections were obtained and stained with toluidine blue and pyronin
      G. Histomorphometric analysis was performed using the NIH Image software. Newly
      formed bone was observed under both resorbable and non-resorbable membranes. The
      amount of regenerated bone was similar between both treatments at 2 and 4 months
      after surgery. At 2 months, the newly formed bone was still immature whereas at 4
      months some areas of woven bone were observed. The bone formation observed in the
      untreated defects was significantly lower than that observed in both resorbable
      and non-resorbable membrane-protected defects. In summary, the present study
      suggests that PLA membranes can yield good results when used on bone defects
      while avoid a second surgical procedure.

PMID- 12182310
TI  - Tailoring the pore architecture in 3-D alginate scaffolds by controlling the
      freezing regime during fabrication.
AB  - The pore architecture in 3-D polymeric scaffoldings plays a critical role in
      tissue engineering as it provides the framework for the seeded cells to organize
      into a functioning tissue. In the present paper, we investigate the effect of
      freezing regime on the pore microstructure in 3-D alginate scaffolds, fabricated
      by the freeze-dry method. The scaffolds have shown isotropic pore structure, when
      the calcium crosslinked alginate solutions were slowly frozen at -20 degrees C,
      in a nearly homogenous cold atmosphere; the pores were spherical and
      interconnected. In contrast, when the cooling process was performed in liquid
      nitrogen or oil bath, where a temperature gradient was formed along the freezing
      solution, two main regions of pore structure were noted; at the interface with
      the cooling medium, small spherical pores were seen and above them a region with
      elongated pores. The different pore shape affected the compressibility of the
      scaffolds, while it had no effect on albumin diffusion. Rat hepatocytes seeded
      within the scaffolds were arranged according to the their pore shape. In
      scaffolds with elongated pores, the cells were lining along the pores, thus
      forming lines of interacting cells. In the scaffolds with the isotropic spherical
      pores, the hepatocytes clustered into spheroid-like aggregates. Thus, it appears
      that pore shape can modulate hepatocyte morphogenesis.

PMID- 12182311
TI  - Optimal design and fabrication of scaffolds to mimic tissue properties and
      satisfy biological constraints.
AB  - Bone tissue engineering scaffolds must shape regenerating tissue, provide
      temporary mechanical support and enhance tissue regeneration. These requirements
      result in conflicting design goals. For example, increased temporary mechanical
      function requires a dense scaffold while enhanced cell/gene delivery requires a
      porous scaffold. This paper demonstrates an image-based homogenization
      optimization approach that can design scaffold microstructure, scaffold material
      and regenerate tissue microstructure to meet conflicting design requirements. In
      addition, constraints to ensure adequate cell/gene delivery can be introduced
      using a minimum porosity threshold. Homogenization theory was used to compute
      relationships between scaffold microstructure and effective stiffness. The
      functional relationships were used in the MATLAB optimization toolbox to compute
      optimal pore dimensions and scaffold material such that the scaffold and
      regenerate tissue effective stiffness matched that of native bone stiffness. The
      scaffold design was converted into STL format for solid free-form fabrication.
      Scaffolds were designed that matched mandibular condyle trabecular bone
      properties. Results showed excellent agreement between native bone properties and
      designed scaffold properties (all R2 > 0.89). Finally, example scaffolds were
      built from hydroxyapatite using a SFF casting technique.

PMID- 12182312
TI  - Etching kinetics of a self-etching primer.
AB  - Self-etching primers are thought to offer significant advantages over total-etch
      adhesive systems. The hypothesis tested in this study was that there was no
      difference in etching characteristics between a self-etching primer and a
      phosphoric acid solution at the same pH. Etching was assessed using atomic force
      microscopy (AFM) evaluation of site-specific changes in the height of the
      peritubular and intertubular dentin as a function of exposure time. Human dentin
      disks (n = 6/group), prepared with an acid-resistant glass reference layer, were
      etched with a self-etching primer and with 0.0134 M phosphoric acid (both pH
      approximately egual to 1.94). Depth changes relative to the reference layer were
      measured with the AFM after each etching interval, at 15 different locations,
      each in the peritubular and intertubular dentin. The total demineralization depth
      was measured in a scanning electron microscope. Peritubular dentin etching rate
      was linear while it could be measured (up to 15 s) and was greater for the self
      etching primer (p < 0.0001). Intertubular dentin displayed a similar
      demineralization pattern with both acids, ultimately reaching a plateau in the
      majority of specimens. The self-etching primer attained a plateau after less
      recession than phosphoric acid (p < 0.0001). Dentin demineralization appears to
      be affected by other factors in addition to the pH of the etchant solutions.

PMID- 12182313
TI  - Effect of CaF2 on densification and properties of hydroxyapatite-zirconia
      composites for biomedical applications.
AB  - Hydroxyapatite (HA) composites with zirconia (ZrO2) up to 40 vol% were fabricated
      with the addition of CaF2. The sinterability of the composites was found to be
      enhanced markedly by the addition of small amounts of CaF2 (< 5 vol%).
      Decomposition of HA to beta-TCP was suppressed due to the substitution of F- for
      OH-, consequently forming fluor-hydroxyapatite (FHA) solid solution. This
      suppression of decomposition allowed the production of a fully dense body, which
      retained both high flexural strength and fracture toughness. The osteoblast-like
      cell (MG63) response to these F- ion-containing composites displayed comparable
      cell viability to pure-HA by in vitro proliferation test.

PMID- 12182314
TI  - Wettability and surface charge of Si3N4-bioglass composites in contact with
      simulated physiological liquids.
AB  - Wettability and surface charge studies were performed on a novel Si3N4-30wt%
      bioglass biocomposite. Contact angle and surface tension variation with time were
      determined at 25 degrees C, respectively, by the sessile and pendant drop
      techniques, for distinct testing liquids: water, diiodomethane, simulated body
      fluid (SBF) and bovine serum albumin (BSA) dissolved in SBF solution. This
      biocomposite revealed a hydrophilic character (theta = 26.6 +/- 2.0 degrees) and
      a surface tension value (66.6 mJ m(-2)) comparatively higher than those of the
      most common bioceramics. An important characteristic is the high work of adhesion
      towards SBF + BSA (96.4 +/- 0.2mJ m(-2)) that was measured. The Si3N4-bioglass
      material is negatively surface charged above the pH(IEP) = 2.5 in aqueous SBF +
      BSA solution, as a result of the presence at the surface of unsaturated Si-O
      bonds and Si-OH groups. The very high negative zeta potential at pH approximately
      7 (-58.6 +/- 5.5mV) influenced albumin adsorption and mechanisms are discussed in
      terms of entropy and enthalpy gains from conformational unfolding and cations
      coadsorption.

PMID- 12182315
TI  - Silk matrix for tissue engineered anterior cruciate ligaments.
AB  - A silk-fiber matrix was studied as a suitable material for tissue engineering
      anterior cruciate ligaments (ACL). The matrix was successfully designed to match
      the complex and demanding mechanical requirements of a native human ACL,
      including adequate fatigue performance. This protein matrix supported the
      attachment, expansion and differentiation of adult human progenitor bone marrow
      stromal cells based on scanning electron microscopy, DNA quantitation and the
      expression of collagen types I and III and tenascin-C markers. The results
      support the conclusion that properly prepared silkworm fiber matrices, aside from
      providing unique benefits in terms of mechanical properties as well as
      biocompatibility and slow degradability, can provide suitable biomaterial
      matrices for the support of adult stem cell differentiation toward ligament
      lineages. These results point toward this matrix as a new option for ACL repair
      to overcome current limitations with synthetic and other degradable materials.

PMID- 12182316
TI  - Incorporation of tobramycin into biomimetic hydroxyapatite coating on titanium.
AB  - Calcium phosphate coatings containing an antibiotic were produced on titanium
      alloy (Ti6Al4V) implants using a biomimetic approach. Thin, amorphous calcium
      phosphate (ACP) coatings were first deposited onto Ti6Al4V plates by immersion in
      5 times concentrated simulated body fluid (SBF), for 24h at 37 degrees C. The ACP
      coated implants were then immersed in a supersaturated calcium phosphate (SCP)
      solution containing 0, 100, 200, 400, 600 or 800 mg/l of tobramycin for 48 h at
      37 degrees C. A carbonated hydroxyapatite (CHA) layer, approximately 40 microm
      thick, was formed. Approximately 3 microg/mg of tobramycin was co-precipitated
      with the CHA crystals onto titanium alloy plates, using 800mg/l tobramycin in the
      coating solution. For comparison, plasma-sprayed calcium phosphate coatings were
      also immersed in solutions containing 100, 200, 400 or 1,000 mg/l of tobramycin
      for 10, 40 min, or 48 h. A maximum of about 0.3 microg/mg could be adsorbed onto
      the plasma-sprayed calcium phosphate coating with the comparable concentration of
      800 mg/l in solution. The dissolution of coating and release of tobramycin were
      also measured in vitro using saline solution buffered at pH 5.0 or 7.3 at 37
      degrees C. The release rate of tobramycin was faster at pH 7.3 than at pH 5, with
      50 and 4 microg/ml/min, respectively. Tobramycin released from the biomimetic
      coated plates could inhibit growth of Staphylococcus aureus bacteria. The result
      of this study, therefore, indicates that the biomimetic CHA coatings containing
      antibiotics could be used to prevent post-surgical infections in orthopaedic or
      trauma.

PMID- 12182317
TI  - Density functional study of structural, electronic and vibrational properties of
      mg- and zn-doped tricalcium phosphate biomaterials.
AB  - Zn- and to a lesser extent Mg-releasing tricalcium phosphate (Zn- and Mg-TCP)
      have excellent bioactivities which do not exist in their parent TCP base.
      However, the mechanisms through which the dopants affect the properties are not
      known. In order to gain insight from geometrical and electronic structures and
      chemical bonding, ab initio density functional calculations have been performed
      for these materials using cluster models. The results show a distorted structure
      for Zn-TCP which may be related to its bioactivity, whereas no such distortion
      was found for TCP and Mg-TCP. The infrared spectra of these materials has been
      calculated, and the relationship to the structure investigated.

PMID- 12182318
TI  - Solution structure of a DNA duplex containing a formamide-adenine base pair.
AB  - The N-(2-deoxy-beta3-D-erythro-pentofuranosyl) formamide residue results from a
      ring fragmentation product of thymine or cytosine. The presence of a formamide
      adenine base pair in the sequence 5'd(AGGAACCACG).d(CGTGGFTCCT) has been studied
      by 1H and 31P nuclear magnetic resonance (NMR) and molecular dynamics. There are
      two possible isomers for the formamide side chain, either cis or trans. For each
      isomer, we observed an equilibrium in solution between two forms. First, a
      species where the formamide is intrahelical and paired with the facing adenine.
      For the cis isomer, the formamide is in a syn conformation and two hydrogen bonds
      with adenine are formed. The trans isomer is in an anti conformation and a single
      hydrogen bond is observed. In the second form, whatever the isomer, the formamide
      is rejected outside the helix, whereas the adenine remains inside.

PMID- 12182319
TI  - Mouse one-cell embryos undergoing a radiation-induced G2 arrest may re-enter S
      phase in the absence of cytokinesis.
AB  - PCC (premature chromosome condensation) can be used for visualizing and scoring
      damage induced by radiation in the chromatin of cells undergoing a G1 or G2
      arrest. A method involving the fusion of irradiated single embryonic cells with
      single MI oocytes was used to induce PCC in mouse zygotes of the BALB/c strain,
      which suffer a drastic G2 arrest after X-irradiation (dose used 2.5 Gy). Other G2
      arrested embryos were exposed in vitro to the phosphatase inhibitor calyculin A.
      Both methods furnished excellent chromosome preparations of the G2-arrested
      embryos. The mean number of chromosome fragments did not change significantly
      during G2 arrest, suggesting that zygotes of this strain are unable to repair DNA
      damage leading to such aberrations. Forty to fifty percent of the irradiated
      embryos were unable to cleave after G2 arrest and remained blocked at the one
      cell stage for a few days before dying. PCC preparations obtained from such
      embryos suggested that about 30% of them had undergone a late mitosis not
      followed by cytokinesis and had entered a new DNA synthesis. These results are
      discussed in the light of recent observations in irradiated human cells deficient
      in the p53/14-3-3sigma pathway.

PMID- 12182320
TI  - Effects of fast neutrons on chromatin: dependence on chromatin structure.
AB  - The effects of fast neutrons (10-100 Gy) on chromatin extracted from normal
      (liver of Wistar rats) and tumor (Walker carcinosarcoma maintained on Wistar
      rats) tissues were compared. The spectroscopic assays used were (i) chromatin
      intrinsic fluorescence, (ii) time-resolved fluorescence of chromatin - proflavine
      complexes, and (iii) fluorescence resonance energy transfer (FRET) between dansyl
      chloride and acridine orange coupled to chromatin. For both normal and tumor
      chromatin, the intensity of intrinsic fluorescence specific for acidic and basic
      proteins decreased with increasing dose. The relative contributions of the
      excited-state lifetime of proflavine bound to chromatin were reduced upon fast
      neutron irradiation, indicating a decrease in the proportion of chromatin DNA
      available for ligand binding. The Forster energy transfer efficiencies were also
      modified by irradiation. These effects were larger for chromatin from tumor
      tissue. In the range 0-100 Gy, fast neutrons induced alterations in DNA and
      acidic and basic proteins, as well as in global chromatin structure. The
      radiosensitivity of chromatin extracted from tumor tissue seems to be higher than
      that of chromatin extracted from normal tissue, probably because of its higher
      euchromatin (loose)--heterochromatin (compact) ratio.

PMID- 12182321
TI  - Radiation could induce p53-independent and cell cycle--unrelated apoptosis in 5
      fluorouracil radiosensitized head and neck carcinoma cells.
AB  - The effect of chemoresistance induction in radiosensitivity and cellular behavior
      after irradiation remains misunderstood. This study was designed to understand
      the relationship between radiation-induced cell cycle arrest, apoptosis, and
      radiosensitivity in KB cell line and KB3 subline selected after 5-fluorouracil
      (5FU) exposure. Exposure of KB cells to 5FU led to an increase in
      radiosensitivity. G2/M cell cycle arrest was observed in the two cell lines after
      irradiation. The radioresistant KB cell line reached the maximum arrest two hours
      before KB3. The cellular exit from this arrest was found to be related to the
      wild type p53 protein expression induction. After irradiation, only KB3 cell line
      underwent apoptosis. This apoptosis induction seemed to be independent of G2/M
      arrest exit, which was carried out later. The difference in radiosensitivity
      between KB and KB3 subline may result therefore from both a difference in
      apoptosis induction and a difference in G2/M arrest maximum duration. Moreover,
      5FU exposure has led to an increase in constitutive p53 protein expression, which
      may be associated with an increase in basal apoptosis cell fraction. Given the
      existing correlation between radiosensitivity and the percentage of basal
      apoptosis, the constitutive p53 protein expression may be related to intrinsic
      radiosensitivity in our cellular model.

PMID- 12182322
TI  - Induction of apoptosis by high linear energy transfer radiation: role of p531.
AB  - The involvement of the tumor suppressor p53 gene in the sensitivity of many cell
      types towards low linear energy transfer (LET) radiation is now well established.
      However, little information is available on the relationship between p53 status
      of tumor cells and their ability to undergo apoptosis following exposure to high
      LET radiation. Here we present the results of experiments carried out with the
      human lymphoblastoid cell line TK6 and its p53 knock-out counterpart NH32. Cells
      were irradiated at doses ranging from 0.25 to 8 Gy with fast neutrons (65 MeV),
      carbon ions (95 MeV/nucleon), and X rays (15 MV). For both cell lines, the
      occurrence of apoptosis, determined by the quantification of hypodiploid
      particles as well as the activation of several caspases, was compared with their
      sensitivity towards high-LET radiation. Results indicate that p53 is involved in
      the response of TK6 cells to fast neutrons and carbon ions, as measured by cell
      proliferation and occurrence of apoptosis. However, p53-deficient cells are still
      able to undergo apoptosis following irradiation. This suggests that heavy ions
      and fast neutrons induce cellular damage that is not under the control of p53.
      The involvement of executioner caspases in high-LET radiation induced apoptosis
      was also evaluated by use of specific inhibitors.

PMID- 12182323
TI  - Inhibition of ultraviolet B (UVB) induced apoptosis in A431 cells by mimosine is
      not dependent on cell cycle arrest.
AB  - Ultraviolet (UV) radiation is a strong apoptotic trigger in many cell types. We
      have previously reported that a plant amino acid, mimosine (beta [N-(3-hydroxy-4
      pyridone)]-alpha-aminopropionic acid), with a well-known reversible G1 cell cycle
      arrest activity can inhibit apoptosis induced by UV irradiation and RNA
      polymerase II blockage in human A431 cells. Here, apoptosis was measured with a
      fluorimetric caspase activation assay. Interestingly, the protective state was
      effective up to 24 h following removal of mimosine from the culture medium while
      cells were progressing in the cell cycle. Our results demonstrate that the
      protective effect of mimosine against UV-induced apoptosis can be dissociated
      from its G1 cell-cycle arrest activity.

PMID- 12182324
TI  - Ultrastructural lesions induced by neptunium-237: apoptosis or necrosis?
AB  - In this study, we are concerned with the 237 isotope of neptunium (237Np), which
      is a by-product of uranium in nuclear reactors. To study ultrastructural lesions
      induced by this element, a group of rats were injected with a solution of 237Np
      nitrate once a day for 14 weeks. Lesions observed in liver and kidney are
      described using electron microscopy. Ultrastructural alterations of cellular
      membranes and intracellular organelles demonstrated the existence of neptunium
      toxicity. This toxicity was characterized by various lesions, such as cytoplasmic
      clarification, disappearance of mitochondrial cristae, swollen mitochondria,
      abnormal condensation of nuclear chromatin, and nuclear fragmentations. This
      study demonstrated the probable induction of apoptosis by neptunium both in liver
      and kidneys.

PMID- 12182325
TI  - Blood-brain barrier permeability after gamma whole-body irradiation: an in vivo
      microdialysis study.
AB  - The effects of total-body irradiation on the permeability of rat striatal blood
      brain barrier (BBB) to [3H]alpha-aminoisobutyric acid (AIBA) and [14C]sucrose
      were investigated using the microdialysis technique. Seven days, 3 and 6 weeks,
      and 3, 5, and 8 months after gamma exposure at a dose of 4.5 Gy, no modification
      of the permeability to both [3H]AIBA and [14C]sucrose was observed. But, in the
      course of the initial syndrome, we observed a significant but transient increase
      in the BBB permeability to the two markers between 3 and 17 h after exposure. A
      secondary transient "opening" of the BBB to [14C]sucrose was noticed about 28 h
      following irradiation without the corresponding increase in BBB permeability to
      [3H]AIBA. On the contrary, the transport of [3H]AIBA through the BBB was
      decreased between 33 and 47 h postradiation. In conclusion, our experiments
      showed early modifications of BBB permeability after a moderate-dose whole-body
      exposure. Confirmation of these results with other tracers, in another
      experimental model or in humans, would have clinical applications for designing
      appropriate pharmacotherapy in radiotherapy and treatment of accidental
      overexposure.

PMID- 12182326
TI  - Potential role of the membrane in the development of intestinal cellular damage
      after whole-body gamma irradiation of the rat.
AB  - Our study emphasizes the effect of gamma irradiation on intestinal cell membrane
      fluidity and addresses the potential relationships existing between radiation
      induced lipoperoxidation, membrane fluidity, and changes in membrane protein
      activities. Male Wistar rats were exposed to an 8-Gy total body irradiation (60Co
      source) and studied 1, 4, and 7 days after irradiation (D1, D4, and D7). Membrane
      enzyme activities and fluorescence anisotropy were determined on small intestinal
      crude membrane preparations. The supernatants of membrane preparations as well as
      plasma were used for malonedialdehyde (MDA) quantification. The effect of
      carbamylcholine on electrical parameters was estimated on distal ileum placed in
      Ussing chambers. We observed a decrease in fluorescence anisotropy for at least 7
      days, an increase in membrane production of MDA at D4, a decrease in membrane
      enzyme activities at D4, but an amplification of carbamylcholine-induced increase
      in short-circuit current at D4 and D7. Furthermore, correlations were observed
      between the 1,6-diphenyl-1,3,5-hexatriene anisotropy coefficient and sucrase
      activity and between MDA levels and leucine aminopeptidase activity. Thus, total
      body irradiation induces changes in intestinal membrane fluidity and an increase
      in lipoperoxidation. These modifications may have an impact on the activity of
      membrane proteins involved in intestinal function.

PMID- 12182327
TI  - Autologous cell therapy as a new approach to treatment of radiation-induced bone
      marrow aplasia: preliminary study in a baboon model.
AB  - The sparing of viable hematopoietic stem and progenitor cells located in
      underexposed bone marrow territories associated with the relative radioresistance
      of certain stem cell populations is the rationale for autologous cell therapy
      consisting of ex vivo expansion of residual cells after collection
      postirradiation. The feasibility of this treatment mainly depends on time
      constraints and hematopoietic cell threshold. We showed in this study that in the
      absence of early-acting mobilizing agent administration, subliminar amounts of
      CD34+ cells can be collected (1 x 10(6) CD34+ cells/100 mL bone marrow or for 1 L
      apheresis) from 6-Gy gamma globally irradiated baboons. Residual CD34+ cells were
      successfully expanded in serum-free medium in the presence of antiapoptotic
      cytokine combination (stem cell factor + FLT-3 ligand + thrombopoietin +
      interleukin 3, 50 ng/mL each, i.e., 4F): KCD34+ = x2.8 and x13.7 (n = 2).
      Moreover, we demonstrated the short-term neutrophil engraftment potential of a
      low-size mixed expanded graft (1.5 x 106 final CD34+cells/kg) issued from the
      coculture of unirradiated (20%) and 2.5-Gy in vitro irradiated (80%) CD34+ cells
      on an allogeneic stromal cell layer in the presence of 4F. Further preclinical
      research needs to be performed to clearly establish this therapeutic approach
      that could be optimized by the early administration of antiapoptotic cytokines.

PMID- 12182328
TI  - Thrombopoietin protects mice from mortality and myelosuppression following high
      dose irradiation: importance of time scheduling.
AB  - Thrombopoietin is the major regulator of platelet production and a stimulator of
      multilineage hematopoietic recovery following irradiation. The efficacy of three
      different schedules of thrombopoietin administration was tested on blood cell
      counts, hematopoietic bone marrow progenitors, and 30-day animal survival in
      C57BL6/J mice receiving a total body irradiation, with doses ranging from 7 to 10
      Gy. A single dose of murine thrombopoietin was injected 2 h before, 2 h after, or
      24 h after irradiation. Thrombopoietin promoted multilineage hematopoietic
      recovery in comparison to placebo up to 9 Gy at the level of both blood cells and
      bone marrow progenitors, whatever the schedule of administration. The injection
      of thrombopoietin 2 h before or 2 h after irradiation equally led to the best
      results concerning hematopoietic recovery. On the other hand, thrombopoietin
      administration promoted 30-day survival up to 9 Gy with the highest efficacy
      obtained when thrombopoietin was injected either 2 h before or 2 h after
      irradiation. However, when its injection was delayed at 24 h, thrombopoietin had
      almost no effect on survival of 9 Gy irradiated mice. Altogether, our results
      show that the time schedule for thrombopoietin injection is of critical
      importance and when thrombopoietin is administered before or shortly after
      irradiation, it efficiently promotes mice survival to supra-lethal irradiation
      (up to 9 Gy) in relation with hematopoietic recovery.

PMID- 12182329
TI  - [The effect of dose distribution on risk of lung cancer after inhalation of
      actinide oxides].
AB  - The aim of this work was to estimate risk of lung tumour occurrence after
      inhalation of actinide oxides from published studies and rat studies in progress.
      For the same delivered dose, the risk increases when homogeneity of irradiation
      increases, i.e., the number of particles deposited after inhalation increases
      (small particles and (or) low specific alpha activity). The dose-effect
      relationships reported appear linear up to a few gray, depending on the aerosol
      considered, and then the slope decreases. This slope, which corresponds with the
      risk, can vary over one order of magnitude depending on the aerosol used. An
      effective threshold at about 1 Gy was not observed for the most homogeneous dose
      distributions. A dosimetric and biological approach is proposed to provide a more
      realistic risk estimate.

PMID- 12182330
TI  - Effect of pre-exposure to beta rays of tritium on some biochemical parameters
      measured in organs of rats subsequently irradiated with fast neutrons.
AB  - The experiment examined biological responses produced by combined sequential
      exposure to low-level tritium contamination, followed by challenging irradiation
      with fast neutrons. Modifications of endogenous antioxidant potential of
      different organs in rats were discussed in relation to tissue radiosensitivity.
      Rats pre-contaminated to 7 cGy and 35 cGy have been additionally irradiated to 1
      Gy with fast neutrons. Lipid peroxide level was determined in liver, kidney,
      small intestine, spleen, bone marrow, and plasma. Reduced glutathione (GSH) level
      and glucose-6-phosphate dehydrogenase (G6PDH) activity were determined in
      erythrocytes. An in vitro thymidine uptake assay was performed in isolated bone
      marrow cells. The lipid peroxide level decreased significantly only in liver and
      kidney from rats pre-exposed to 35 cGy. For small intestine and spleen, tissues
      of comparatively higher radiosensitivity, no induced radioprotection was
      observed, as reflected in the homeostasis of the lipid peroxides. The same
      behavior was observed in bone marrow, the most radiosensitive tissue studied.
      However, the bone marrow thymidine-incorporation assay revealed a possible
      adaptive-type reaction in rats pre-exposed to 35 cGy. We conclude that for
      radiosensitive tissues pre-exposure to chronic low doses of low linear energy
      transfer (LET) irradiation has no protective effect on their antioxidant status,
      whereas a protective effect is observed in radioresistent tissues.

PMID- 12182331
TI  - Ingestion of double-stranded RNA by preparasitic juvenile cyst nematodes leads to
      RNA interference.
AB  - RNA interference is of value in determining gene function in many organisms.
      Plant parasitic nematodes are refractory to microinjection as a means of
      introducing RNA and do not show any oral uptake until they are within plants. We
      have used octopamine to stimulate uptake by preparasitic second stage juveniles
      of two cyst nematodes, Heterodera glycines and Globodera pallida. This new
      technique was used to facilitate uptake of double stranded RNA (dsRNA) together
      with fluoroscein isothiocyanate as a visual marker. Targeting cysteine
      proteinases did not reduce the number of parasites but caused a shift from the
      normal female/male ratio of 3:1 to 1:1 by 14 days postinfection (dpi). Exposure
      of H. glycines to dsRNA corresponding to a newly characterized protein with
      homology to C-type lectins did not affect sexual fate, but 41% fewer parasites
      were recovered from the plants. As expected, treatment with dsRNA corresponding
      to the major sperm protein (MSP) had no effect on either parasite development or
      sexual fate over 14 days. Northern analysis showed lower transcript abundance for
      the two targeted mRNAs that occur in J2, plus a later inhibition for MSP
      transcripts when males developed sperm at 15 dpi. These findings establish a
      procedure for RNAi of plant parasitic nematodes.

PMID- 12182332
TI  - Sequence-, tissue-, and delivery-specific targeting of RNA during post
      transcriptional gene silencing.
AB  - Transgenic Nicotiana benthamiana plants expressing an untranslatable version of
      the coat protein (CP) gene from the Tamarillo mosaic virus (TaMV) were either
      resistant to TaMV infection or recovered from infection. These phenotypes were
      the result of a post-transcriptional gene silencing (PTGS) mechanism that
      targeted TaMV-CP sequences for degradation. The TaMV-CP sequences were degraded
      when present in the wild-type TaMV potyvirus, in transgene mRNA, or in chimeric
      viral vectors based on White clover mosaic virus. The more efficiently targeted
      region was mapped to a 134-nt segment. Differences were observed in the
      efficiency of targeting during cell-to-cell and long-distance movement of the
      chimeric viruses. However, the TaMV-CP sequences do not appear to be targeted for
      degradation when delivered by biolistics.

PMID- 12182333
TI  - Constitutive expression of hrap gene in transgenic tobacco plant enhances
      resistance against virulent bacterial pathogens by induction of a hypersensitive
      response.
AB  - Hypersensitive response-assisting protein (HRAP) has been previously reported as
      an amphipathic plant protein isolated from sweet pepper that intensifies the
      harpin(Pss)-mediated hypersensitive response (HR). The hrap gene has no
      appreciable similarity to any other known sequences, and its activity can be
      rapidly induced by incompatible pathogen infection. To assess the function of the
      hrap gene in plant disease resistance, the CaMV 35S promoter was used to express
      sweet pepper hrap in transgenic tobacco. Compared with wild-type tobacco,
      transgenic tobacco plants exhibit more sensitivity to harpin(Pss) and show
      resistance to virulent pathogens (Pseudomonas syringae pv. tabaci and Erwinia
      carotovora subsp. carotovora). This disease resistance of transgenic tobacco does
      not originate from a constitutive HR, because endogenous level of salicylic acid
      and hsr203J mRNA showed similarities in transgenic and wildtype tobacco under
      noninfected conditions. However, following a virulent pathogen infection in hrap
      transgenic tobacco, hsr203J was rapidly induced and a micro-HR necrosis was
      visualized by trypan blue staining in the infiltration area. Consequently, we
      suggest that the disease resistance of transgenic plants may result from the
      induction of a HR by a virulent pathogen infection.

PMID- 12182334
TI  - pH regulates endoglucanase expression and virulence of Alternaria alternata in
      persimmon fruit.
AB  - The phytopathogenic fungus Alternaria alternata produces one endo-1,4-beta
      glucanase, AaK1, which is an important factor in disease development in persimmon
      fruit. During growth of A. alternata in media containing acidified yeast extract
      or cell walls from persimmon fruit, the fungus secreted ammonia and raised the
      medium pH. A rise in media pH from 3.8 to 6.0 in the presence of cell walls
      induced the expression of AaK1, whereas a glucose-induced decline in pH to 2.5
      repressed transcription and enzymatic production. Treatments with buffered
      solutions at pH 6.0 during growth of A. alternata in the presence of glucose
      derepressed AaK1 expression and endo-1,4-beta-glucanase production and enhanced
      decay development on the fruit. The results suggest that conditions affecting
      environmental pH modulate gene expression of AaK1 and virulence of A. alternata
      in persimmon fruit

PMID- 12182335
TI  - Extending chestnut blight hypovirus host range within diaporthales by biolistic
      delivery of viral cDNA.
AB  - Biolistic bombardment was used to successfully transform three phytopathogenic
      fungal species with an infectious cDNA clone of the prototypic hypovirus, CHV1
      EP713, a genetic element responsible for the virulence attenuation
      (hypovirulence) of the chestnut blight fungus, Cryphonectria parasitica. The
      fungal species included two strains each of C. parasitica and Valsa ceratosperma,
      as well as one strain of Phomopsis G-type (teleomorph Diaporthe Nitschke); all
      are members of the order Diaporthales but classified into three different genera.
      A subset of transformants for each of the fungal species contained CHV1-EP713
      dsRNA derived from chromosomally integrated viral cDNA. As has been reported for
      CHV1-EP713 infection of the natural host C parasitica, biolistic introduction of
      CHV1-EP713 into the new fungal hosts V ceratosperma and Phomopsis G-type resulted
      in altered colony morphology and, more importantly, reduced virulence. These
      results suggest a potential for hypoviruses as biological control agents in plant
      infecting fungal pathogens other than the chestnut blight fungus and closely
      related species. In addition, the particle delivery technique offers a convenient
      means of transmitting hypoviruses to potential host fungi that provides new
      avenues for fundamental mycovirus research and may have practical applications
      for conferring hypovirulence directly on infected plants in the field.

PMID- 12182336
TI  - Oomycete plant pathogens use electric fields to target roots.
AB  - Plant roots generate electrical currents and associated electrical fields as a
      consequence of electrogenic ion transport at the root surface. Here we
      demonstrate that the attraction of swimming zoospores of oomycete plant pathogens
      to plant roots is mediated in part by electrotaxis in natural root-generated
      electric fields. The zones of accumulation of anode- or cathode-seeking zoospores
      adjacent to intact and wounded root surfaces correlated with their in vitro
      electrotactic behavior. Manipulation of the root electrical field was reflected
      in changes in the pattern of zoospore accumulation and imposed focal electrical
      fields were capable of overriding endogenous signals at the root surface. The
      overall pattern of zoospore accumulation around roots was not affected by the
      presence of amino acids at concentrations expected within the rhizosphere,
      although higher concentrations induced encystment and reduced root targeting. The
      data suggest that electrical signals can augment or override chemical ones in
      mediating short-range tactic responses of oomycete zoospores at root surfaces.

PMID- 12182337
TI  - Virus-induced gene silencing in transgenic plants expressing the minor capsid
      protein of Beet western yellows virus.
AB  - Transgenic Nicotiana benthamiana expressing the minor coat protein P74 of the
      phloem-limited Beet western yellows virus (BWYV) exhibited an unusual spatial
      pattern of post-transcriptional gene silencing (PTGS) when infected with BWYV or
      related viruses. Following infection, transgenic P74 and its mRNA accumulated to
      only low levels, 21 to 23 nucleotide RNAs homologous to the transgene appeared,
      and the transgene DNA underwent methylation. The infecting viral RNA, however,
      was not subject to significant silencing but multiplied readily and produced P74
      in the phloem tissues, although the P74 encoded by the transgene disappeared from
      the phloem as well as the nonvascular tissues.

PMID- 12182338
TI  - Differential expression of genes encoding Arabidopsis phospholipases after
      challenge with virulent or avirulent Pseudomonas isolates.
AB  - Phospholipase D (PLD; EC 3.1.4.4) has been linked to a number of cellular
      processes, including Tran membrane signaling and membrane degradation. Four PLD
      genes (alpha, beta, gamma1, and gamma2) have been cloned from Arabidopsis
      thalami. They encode isoforms with distinct regulatory and catalytic properties
      but little is known about their physiological roles. Using cDNA amplified
      fragment length polymorphism display and RNA blot analysis, we identified
      Arabidopsis PLDgamma1 and a gene encoding a lysophospholipase (EC 3.1.1.5),
      lysoPL1, to be differentially expressed during host response to virulent and
      avirulent pathogen challenge. Examination of the expression pattern of
      phospholipase genes induced in response to pathogen challenge was undertaken
      using the lysoPL1 and gene-specific probes corresponding to the PLD isoforms a,
      beta, and gamma1. Each mRNA class exhibited different temporal patterns of
      expression after infiltration of leaves with Pseudomonas syringae pv. tomato with
      or without avrRpm1. PLDalpha was rapidly induced and remained constitutively
      elevated regardless of treatment. PLDbeta was transiently induced upon pathogen
      challenge. However, mRNA for the lysoPL1 and PLDgamma1 genes showed enhanced and
      sustained elevation during an incompatible interaction, in both ndr1 and
      overexpressing NahG genetic backgrounds. Further evidence for differential
      engagement of these PLD mRNA during defense responses, other than gene-for-gene
      interactions, was demonstrated by their response to salicylic acid treatment or
      wounding. Our results indicate that genes encoding lysoPL1, PLDgamma1, and
      PLDbeta are induced during early responses to pathogen challenge and,
      additionally, PLDyl and lysoPL1 are specifically upregulated during gene-for-gene
      interactions, leading to the hypersensitive response. We discuss the possible
      role of these genes in plant-pathogen interactions.

PMID- 12182339
TI  - Mutation of rpiA in Enterobacter cloacae decreases seed and root colonization and
      biocontrol of damping-off caused by Pythium ultimum on cucumber.
AB  - Strains of Enterobacter cloacae show promise as biocontrol agents for Pythium
      ultimum-induced damping-off on cucumber and other crops. E. cloacae A145 is a
      mini-Tn5 Km transposon mutant of strain 501R3 that was significantly reduced in
      suppression of damping-off on cucumber caused by P. ultimum. Strain A145 was
      deficient in colonization of cucumber, sunflower, and wheat seeds and
      significantly reduced in colonization of corn and cowpea seeds relative to strain
      501R3. Populations of strain A145 were also significantly lower than those of
      strain 501R3 at all sampling times in cucumber, wheat, and sunflower rhizosphere.
      Populations of strain A145 were not detectable in any rhizosphere after 42 days,
      while populations of strain 501R3 remained at substantial levels throughout all
      experiments. Molecular characterization of strain A145 indicated mini-Tn5 Km was
      inserted in a region of the E. cloacae genome with a high degree of DNA and amino
      acid sequence similarity to rpiA, which encodes ribose-5-phosphate isomerase. In
      Escherichia coli, RpiA catalyzes the interconversion of ribose-5-phosphate and
      ribulose-5-phosphate and is a key enzyme in the pentose phosphate pathway. Ribose
      5-phosphate isomerase activity in cell lysates from strain A145 was approximately
      3.5% of that from strain 501R3. In addition, strain A145 was a ribose auxotroph,
      as expected for an rpiA mutant. Introduction of a 1.0-kb DNA fragment containing
      only the rpiA homologue into strain A145 restored ribose phosphate isomerase
      activity, prototrophy, seedling colonization, and disease suppression to levels
      similar to those associated with strain 501R3. Experiments reported here indicate
      a key role for rpiA and possibly the pentose phosphate pathway in suppression of
      damping-off and colonization of subterranean portions of plants by E. cloacae.

PMID- 12182340
TI  - The occurrence of CMV-specific short Rnas in transgenic tobacco expressing virus
      derived double-stranded RNA is indicative of resistance to the virus.
AB  - Expression or introduction of double-stranded (ds)RNA in eukaryotic cells can
      trigger sequence-specific gene silencing of transgenes, endogenes, and viruses.
      Transgenic plants producing dsRNAs with homology to viral sequences are likely to
      exhibit pathogen-derived resistance to the virus. Cucumber mosaic virus (CMV), a
      very widespread virus with over 1,000 host species, has the natural ability to
      suppress silencing in order to establish infection. Here, we report the
      generation of transgenic tobacco lines, where a DNA transgene containing an
      inverted repeat of CMV cDNA had been introduced. Expression of this DNA construct
      delivered an RNA transcript that is able to form an intramolecular double strand.
      Transgenic plants were challenged with CMV. Three categories of plants could be
      discriminated: susceptible plants, which typically reacted with milder symptoms
      than the wild-type control; a "recovery" phenotype, in which newly emerging
      leaves were free of symptoms; and plants that showed complete resistance.
      Northern analysis showed that the expression of CMV dsRNA caused, in some
      transgenic lines, the generation of short RNAs characteristic of
      posttranscriptional gene silencing. Those lines were CMV resistant. The
      correlation between the detection of short RNAs and virus resistance provides a
      molecular marker that makes it possible to predict success in attempts to
      engineer virus resistance by dsRNA.

PMID- 12182341
TI  - High-affinity nod factor binding site from Phaseolus vulgaris cell suspension
      cultures.
AB  - The lipo-chitooligosaccharidic Nod factors produced by rhizobia are key molecules
      in the establishment of symbiosis with legumes and probably are recognized by the
      host plant via specific receptors. Here, we report on the presence of a binding
      site in cell cultures of Phaseolus vulgaris displaying a high affinity for Nod
      factors from Rhizobium tropici (NodRt-V) (Me, S, C18:1), a symbiont of this
      legume. The binding site shares common properties with NFBS2, a Nod-factor
      binding site previously characterised in Medicago varia, in terms of affinity,
      preferential plasma-membrane location, and sensitivity to proteases and lysine
      reactive reagents. However, the bean site poorly recognizes the Nod factors
      produced by Sinorhizobium meliloti, the symbiont of Medicago. The study of
      selectivity toward the Nod factors reveals that the length and degree of
      unsaturation of the acyl chain and the length of the oligosaccharidic moiety are
      important determinants of high affinity binding to the bean site; whereas, the N
      methyl and O-sulfuryl groups play a minor role. Thus, the common characteristics
      of P. vulgaris and M. varia Nod-factor binding sites suggest that they probably
      correspond to structurally related proteins, but their different selectivity
      suggests that they may be involved in a differential perception system for Nod
      factors in legumes.

PMID- 12182342
TI  - Pisatin demethylase genes are on dispensable chromosomes while genes for
      pathogenicity on carrot and ripe tomato are on other chromosomes in Nectria
      haematococca.
AB  - Studies on the wide-host-range fungus Nectria haematococca MP VI have shown a
      linkage between virulence on pea and five of nine PDA genes that encode the
      ability to detoxify the pea phytoalexin, pisatin. Most of the PDA genes are on
      chromosomes of approximately 1.6 megabases (Mb) and two of these genes, PDA1-2
      and PDA6-1, have been demonstrated to reside on approximately 1.6-Mb chromosomes
      that can be lost during meiosis. Prior studies also have shown that the
      dispensable chromosome carrying PDA6-1 contains a gene (MAK1) necessary for
      maximum virulence on chickpea. The present study evaluated whether the other
      approximately 1.6-Mb chromosomes that carry PDA genes also are dispensable, their
      relationship to each other, and whether they contain genes for pathogenicity on
      hosts other than pea or chickpea. DNA from the PDA1-1 chromosome (associated with
      virulence on pea) and the PDA6-1 chromosome (associated with virulence on
      chickpea) were used to probe blots of contour-clamped homogeneous electric field
      (CHEF) gels of isolates carrying different PDA genes and genetically related Pda-
      isolates. All of the approximately 1.6-Mb PDA-bearing chromosomes hybridized with
      both probes, indicating that they share significant similarity. Genetically
      related Pda-progeny lacked chromosomes of approximately 1.6 Mb and there was no
      significant hybridization of any chromosomes to the PDA1-1 and PDA6-1 chromosome
      probes. When isolates carrying different PDA genes and related Pda- isolates were
      tested for virulence on carrot and ripe tomato, there was no significant
      difference in lesion sizes produced by Pda+ and Pda- isolates, indicating that
      genes for pathogenicity on these hosts are not on the PDA-containing chromosomes.
      These results support the hypothesis that the chromosomes carrying PDA genes are
      dispensable and carry host-specific virulence genes while genes for pathogenicity
      on other hosts are carried on other chromosomes.

PMID- 12182343
TI  - Transcript profiling in the barley mildew pathogen Blumeria graminis by serial
      analysis of gene expression (SAGE).
AB  - The fungal pathogen Blumeria graminis f. sp. hordei develops on the barley leaf
      via distinct, morphologically well-defined stages. After landing on a host plant,
      the conidia rapidly germinate to form a primary germ tube. Subsequently, an
      appressorial germ tube emerges from the conidium and differentiates an
      appressorium from which penetration of the host cell wall is attempted. We have
      used serial analysis of gene expression to provide a measurement of messenger RNA
      contents in ungerminated conidia, during conidial germination, and during
      appressorium formation. The resulting data provide a resource for the
      characterization of changes in transcript accumulation during early development
      of B. graminis.

PMID- 12182344
TI  - Sulfoxide-metal exchange for the synthesis of the 2'-tributylstannyl derivative
      of 2',3'-didehydro-2',3'-dideoxyuridine (d4u): a general entry to 2'-carbon
      substituted analogues of d4U.
AB  - Methods are described for the synthesis of the 2'-tributylstannyl derivative of
      2',3'-didehydro-2',3'-dideoxyuridine (d4U). Two approaches were investigated:
      radical-mediated desulfonylative stannylation of the 2'-benzenesulfonyl
      derivative of d4U and sulfoxide-metal exchange reaction of the 2'-benzenesulfinyl
      derivative. The latter approach was found to give the desired 2'-stannyl
      derivative in good yield. It was also shown that manipulations of the stannyl
      group allowed the introduction of a variety of carbon-substituents to the 2'
      position by applying the Stille reaction. The whole reaction sequence has opened
      up a highly general entry to 2'-carbon-substituted analogues of d4U.

PMID- 12182345
TI  - Pyrimidinethione nucleosides and their deaza analogues.
AB  - The methods of preparation, structure, chemical properties and synthetic
      potentiality of pyrimidinethione nucleosides and their deaza analogues are
      reported.

PMID- 12182346
TI  - Unsaturated fluoroketonucleosides as anticancer agents: the synthesis and
      biological activity of 5-fluoro-1-(3,4-di-deoxy-3-fluoro-6-O-trityl-beta-d
      glycero-hex-3-eno-pyranos-2- ulosyl) uracil.
AB  - Direct oxidation of 5-fluoro-1-(4-O-acetyl-3-deoxy-3-fluoro-6-O-trityl-beta-D
      glucopyranosyl) uracil 9 led to the title compound 10 after a beta-elimination
      reaction. The formation of the hydrate of ketone 10 due to the highly
      electronegative fluorine atom in the a position to the carbonyl group, prompted
      us to carry out a comparative study of different methods of oxidation and to
      define the best strategy for the synthesis of such molecules. Results of in vitro
      and in vivo biological evaluations are reported.

PMID- 12182347
TI  - Synthesis of thiaazaheterocycle nucleoside analogues.
AB  - The syntheses of thiazinone, thiazinedione and thiazolinone base modified
      nucleoside analogues have been discussed in both the deoxy- and ribosyl series.
      Both inter- and intramolecular N-glycosylations were evaluated.

PMID- 12182348
TI  - New glycosyl-(carboxamide)-1,2,3-triazole-N-nucleosides: synthesis and antitumor
      activity.
AB  - A series of potential bioactive compounds, 1-glucopyranosyl- 1,2,3-triazole-4,5
      dimethylcarboxylate, 1-glucopyranosyl-1,2,3-triazole-4,5-N-dicarboxamide,-dialkyl
      dicarboxamide-N-nucleosides and 6-amino-4H-1-(beta-D-glucopyranosyl)-8-hydroxy
      1,2.3-triazolo[4,5-e][1,3]-diazepin-4-one, were synthesized. Primary activity
      screening of the novel nucleosides showed poor or no anticancer activity against
      breast, lung and CNS tumors.

PMID- 12182349
TI  - Synthesis of 1-(2-hydroxy-3-methoxypropyl)uracils and their activity against
      L1210 and macrophage raw 264.7 cells.
AB  - The title compounds were obtained from appropriate 5-substituted uracil
      derivatives and 1,2-oxy-3-methoxypropane in the presence of sodium hydride. Under
      similar conditions 5-iodouracil gave 2-methoxymethyl-2,3-dihydro-oxazolo[3,2
      c]pyrimidine-5,7-dione as a result of intramolecular cine type nucleophilic
      substitution. Cytotoxicity of 1-(2-hydroxy-3-methoxypropyl)-5-substituted uracil
      derivatives against L1210 and macrophage RAW 264.7 cells in vitro was examined.

PMID- 12182350
TI  - Synthesis and characterization of nucleoside derivatives, n-(benzoyl)-n
      (deoxyguanosin-8-yl)4-aminobiphenyl and n-(2'-deoxyguanosin-8-yl)4-aminobiphenyl
      via alpha-phenyl-n-(4-biphenyl)nitrone.
AB  - Lead tetraacetate (LTA) oxidation of alpha-Phenyl-N-(4-bipheny])nitrone (8) to
      give a new ultimate carcinogen, N-acetoxy-N-benzoyl-4-aminobiphenyl (9) which was
      reacted with deoxyguanosine (dG) at pH 6.9 to give nucleoside derivative, N
      (benzoyl)-N-(deoxyguanosin-8-yl)-4-aminobiphenyl (10). Following debenzoylation
      with sodium carbonate-methanol leads to N-(2'-deoxyguanosin-8-yl)-4-aminobiphenyl
      (11).

PMID- 12182351
TI  - Microwave assisted high yielding preparation of N-protected 2'
      deoxyribonucleosides useful for oligonucleotide synthesis.
AB  - A rapid and high yielding method for the synthesis of precursors of synthons for
      DNA synthesis, N-protected 2'-deoxyribonucleosides is described, which occur
      under mild conditions using microwave irradiation. The desired material, N
      protected nucleosides, was obtained in 93-96% yield in few minutes. The final
      products were then characterized by 1H-NMR and MALDI-TOF and compared with the
      standard samples. The method is amenable to small to moderate scale of synthesis.

PMID- 12182352
TI  - Reaction of glycosyl isothiocynates with 3-indolylaminomethyl-ketone
      hydrochloride.
AB  - Reaction of glycosyl isothiocyanate la-c with 3-indolylaminomethylketone
      hydrochloride(2) yielded glycosylthiourea derivatives 3a-c. Cyclodehydration of
      3a-c with acetic anhydride afforded 5-(indol-3-yl)-2-[N-per-O-acetyl-D
      glycopyranosyl)amino]thiazoles 4a-c. Deacetylation of 4a-c gave 5-(indol-3-yl)-2
      [N-(D-glycopyranosyl) amino] thiazoles 5a-c.

PMID- 12182353
TI  - Fertilization efficiency of in vitro matured oocytes transferred to oviducts of
      inseminated goats: a model to assess in vivo fertilization performance of goat
      spermatozoa.
AB  - An alternative to conventional in vivo validation of sperm assays might be to
      assess the fertilization rate of multiple oocytes transferred to the oviducts of
      inseminated females. Increasing the number of oocytes increases the egg-sperm
      ratio in the oviduct under an unaltered endocrine milieu, setting the basis for
      picking up statistical differences between treatments in small populations. The
      study evaluated the model by transferring oocytes to females inseminated under
      conditions that are known to modify the fertilization rate in the field. The
      study then evaluated the use of cattle oocytes to replace goat oocytes for
      assessing sperm function under this model. In Experiment 1, 12 females were
      inseminated at estrus with either 100 or 300 million spermatozoa 20 h before
      transferring homologous oocytes into the oviduct ipsilateral to the ovulation
      point. In Experiment 2, 10 females were inseminated either once or twice; 10-20 h
      later, homologous oocytes were transferred into the oviduct ipsilateral to the
      ovulation point. In Experiment 3, 13 bilateral-ovulated females were inseminated
      and 20 h later goat and cattle oocytes were transferred to contralateral
      oviducts. Then, 16-20 h later, oocytes were flushed from the oviduct, cleaned of
      spermatozoa and stained to assess the fertilization rate. The fertilization rate
      was improved by increasing sperm numbers at insemination (P < 0.04) and by
      increasing the number of inseminations (P < 0.02). The results in Experiment 3
      showed that fertilization rates were similar for goat and cattle oocyte (P >
      0.05) and that fertilization values were highly correlated (r = 0.811, P <
      0.001). Results suggest that the model can be used for in vivo validation of in
      vitro sperm assays by facilitating the expression of statistical differences in
      small number of animals. In addition, cattle oocytes can be used to replace goat
      oocytes to study in vivo sperm function in goats.

PMID- 12182354
TI  - Reproductive performance of early-weaned female swine according to their estrus
      profile and frequency of artificial insemination.
AB  - We determined the estrus profile (weaning-to-estrus interval (WEI), estrus
      duration (ED), and frequency of estrus per detection period) in 184 female swine
      and estimated the effect of the WEI, ED and frequency of artificial insemination
      (AI) on farrowing rate (FR) and litter size. Estrus detection was done at 8:30
      a.m. and 5:00 p.m. The WEI was categorized as short (<100 h), medium (100-120 h)
      and long (>120 h). The ED was categorized as short (<60 h), medium (60-72 h) and
      long (>72 h). Mean lactation length was 14.6 days, mean WEI was 124.5 h and mean
      ED was 69 h. In each weaning group, females received either one or two AI,
      following a breeding schedule based on the estrus profile. In single-mated
      females, Al was performed 36 h after the beginning of estrus. In double-mated
      females, the first AI was done 24 h after the beginning of estrus and the second
      AI occurred 12 h later. The period of estrus detection had no effect (P > 0.05)
      on WEI, ED, FR, total born (TB) and live born litter size (LB). Mean FR was
      82.6%, mean TB was 10.0% and mean LB was 9.2%. Mean ED was shorter (P < 0.03) for
      females having medium and long WEI (67.0 and 65.4 h, respectively) than for those
      having short WEI (72.2 h). A linear regression analysis identified a weak (R2 =
      0.02) but significant negative association between ED and WEI (P = 0.05). The WEI
      did not influence FR (P > 0.05). Total litter size for females having short WEI
      (9.4) was lower (P < 0.03) than for those having long WEI (10.4). Also, LB for
      females having medium and long WEI (9.7-9.8) was higher (P < 0.05) than for those
      having short WEI (8.7). AI frequency had no effect on FR (P > 0.05). TB and LB
      litter size were lower (P < 0.05) for single-mated females (9.6 and 9.0,
      respectively) than for double-mated females (10.7 and 9.6, respectively). Double
      Al was associated with higher subsequent litter size. However, breeding schedules
      based only on estrus profile may not be precise in determining ideal breeding
      time, since females having short WEI had the longest ED and produced the lowest
      litter size.

PMID- 12182355
TI  - Evidence for sulfatase and 17beta-hydroxysteroid dehydrogenase type 1 activities
      in equine epididymis and uterus.
AB  - Our previous work showed that stallion testis produces high amounts of estrogens
      which are subsequently found in the ejaculate. These estrogens are mainly
      synthesized by testicular aromatase, and the major estrogen produced is estrone
      sulfate (E1S). The objective of this study was to investigate the potential role
      of E1S as a source of estrogens in the male and female horse reproductive tracts
      by determining whether both estrone sulfatase (Sulf) and 17beta-hydroxysteroid
      dehydrogenase type I (17beta-HSD1) activities were present in equine testes,
      epididymis and uterus. We assessed E1S bioconversion into estrone (E1) and
      estradiol (E2) in these tissues. Both Sulf and 17beta-HSD1 activities were well
      detected in the cauda epididymis and uterus. Additionally, Sulf activity was
      present in the distal corpus of the epididymis, and 17beta-HSDI in the proximal
      corpus. In contrast, aromatase gene expression, measured as an internal control
      of endogenous estrogen production, had high activity only in the testis. We found
      that seminal E1S of testicular origin can be metabolized to E2, especially in the
      cauda epididymis and uterus. Because E2 appears to play a major role in male and
      female reproduction, we propose that the bioconversion of seminal E1S could
      affect male and female fertility.

PMID- 12182356
TI  - Use of naloxone challenge to predict sexual performance of rams before the fall
      breeding season.
AB  - Serving capacity tests (SCT) identify rams as sexually active, sexually inactive,
      or low sexual performers. Labor and time requirements make SCT impractical and
      expensive. Therefore, a hormone-based test for libido was developed using the
      responses of LH and testosterone (T) after naloxone. This test effectively
      identified sexually active and inactive rams during the breeding season (November
      and December). The current study evaluated the effectiveness of this method at a
      different time of the year. Objectives were to determine if the blood test can
      detect differences in libido during late July and August, and to characterize LH
      and T profiles up to 120 min postnaloxone treatments at this time of year. Two
      experiments were conducted using i.v. naloxone at 0.75 mg/kg BW. Sexually active
      (SA) and sexually inactive (SIA) rams were identified using SCT. In Experiment 1,
      16 SA and 18 SIA rams of several breeds were identified based on SCT conducted
      before naloxone tests. In Experiment 2, 72 Suffolk x white face rams were given
      SCT after naloxone tests and were of unknown sexual activity at the time of the
      naloxone tests. Mixed model analyses for repeated measures with repeated factors
      (month and sample time) and a covariate for mean LH or T before naloxone
      treatment were used for LH and T data. Proc Logistics modeled probabilities that
      rams were sexually active. The LH response to naloxone increased but did not
      differ (P > 0.09) by ram class (SA or SIA) or month. The T response peaked 75-90
      min after naloxone treatment and was still elevated at 120 min. Testosterone
      differed (P < 0.03) for ram class by month by time in Experiment I and differed
      (P < 0.01) between months in Experiment 2. Proc Logistics incorrectly indicated
      that SA and SIA rams were all sexually active. This study indicates that the
      naloxone challenge test cannot discriminate between SA and SIA rams during July
      and August. Further research is required to determine the time of year when this
      sire identification test for libido has significant accuracy.

PMID- 12182357
TI  - Evaluation of a porcine zona pellucida vaccine for the immunocontraception of
      domestic kittens (Felis catus).
AB  - With a seasonally polyestrus breeding structure, the unwanted domestic cat
      population has proven difficult to control. Various lethal methods have been used
      in an attempt to lower this population of cats. Recently, humane attempts to
      control "pest species," such as the feral cat, have focused on
      immunocontraception. SpayVacTM is a vaccine that uses antibodies raised against
      porcine (ZP) antigens to prevent fertilization of the ovum. SpayVac, delivered in
      a single dose, has been evaluated in fallow deer and several species of seals
      with >90% reduction in fertility and no adverse reactions. This study evaluated
      the effectiveness of SpayVac in reducing fertility in domestic kittens. Thirty
      female kittens were treated with SpayVac containing either Freund's complete
      adjuvant (FCA) or alum, or with a control vehicle. Kittens were monitored for
      side effects, estrus cycling at maturity, and fecundity. Anti-porcine ZP
      antibodies were quantified by ELISA. Immunohistochemical assays measured the
      species specificity of the antibodies produced and IgG binding in vivo. Despite
      high anti-porcine ZP antibody titers, neither formulation of SpayVac prevented
      estrus cycling at maturity or reduced fecundity. Immunohistochemical assays
      indicated that antibodies produced by cats treated with SpayVac recognized
      porcine ZP, but not feline ZP.

PMID- 12182358
TI  - Strategies to improve the ovarian response to equine pituitary extract in cyclic
      mares.
AB  - Equine pituitary extract (EPE) has been reported to induce heightened follicular
      development in mares, but the response is inconsistent and lower than results
      obtained in ruminants undergoing standard superovulatory protocols. Three
      separate experiments were conducted to improve the ovarian response to EPE by
      evaluating: (1) effect of increasing the frequency or dose of EPE treatment; (2)
      use of a potent gonadotropin-releasing hormone agonist (GnRH-a) prior to EPE
      stimulation; (3) administration of EPE twice daily in successively decreasing
      doses. In the first experiment, 50 mares were randomly assigned to one of four
      treatment groups. Mares received (1) 25 mg EPE once daily; (2) 50 mg EPE once
      daily; (3) 12.5 mg EPE twice daily; or (4) 25 mg EPE twice daily. All mares began
      EPE treatment 5 days after detection of ovulation and received a single dose of
      cloprostenol sodium 7 days postovulation. EPE was discontinued once half of a
      cohort of follicles reached a diameter of >35 mm and hCG was administered. Mares
      receiving 50 mg of EPE once daily developed a greater number (P = 0.008) of
      preovulatory follicles than the remaining groups of EPE-treated mares, and more
      (P = 0.06) ovulations were detected for mares receiving 25 mg EPE twice daily
      compared to those receiving either 25 mg EPE once daily and 12.5 mg EPE twice
      daily. Embryo recovery per mare was greater (P = 0.05) in the mares that received
      12.5 mg EPE twice daily than those that received 25 mg EPE once daily. In
      Experiment 2, 20 randomly selected mares received either 25 mg EPE twice daily
      beginning 5 days after a spontaneous ovulation, or two doses of a GnRH-a agonist
      upon detection of a follicle >35 mm and 25 mg EPE twice daily beginning 5 days
      after ovulation. Twenty-four hours after administration of hCG, oocytes were
      recovered by transvaginal aspiration from all follicles >35 mm. No differences
      were observed between groups in the numbers of preovulatory follicles generated
      (P = 0.54) and oocytes recovered (P = 0.40) per mare. In Experiment 3, 18 mares
      were randomly assigned to one of two treatment groups. Then, 6-11 days after
      ovulation, mares were administered a dose of PGF2, and concomitantly began twice
      daily treatments with EPE given in successively declining doses, or a dose of
      PGF2alpha, but no EPE treatment. Mares administered EPE developed a higher (P =
      0.0004) number of follicles > or = 35 mm, experienced more (P = 0.02) ovulations,
      and yielded a greater (P = 0.0006) number of embryos than untreated mares. In
      summary, doubling the dose of EPE generated a greater ovarian response, while
      increasing the frequency of treatment, but not necessarily the dose, improved
      embryo collection. Additionally, pretreatment with a GnRH-a prior to ovarian
      stimulation did not enhance the response to EPE or oocyte recovery rates.

PMID- 12182360
TI  - Pregnancy rates following timed embryo transfer with fresh or vitrified in vitro
      produced embryos in lactating dairy cows under heat stress conditions.
AB  - Timed embryo transfer (TET) using in vitro produced (IVP) embryos without estrus
      detection can be used to reduce adverse effects of heat stress on fertility. One
      limitation is the poor survival of IVP embryos after cryopreservation. Objectives
      of this study were to confirm beneficial effects of TET on pregnancy rate during
      heat stress as compared to timed artificial insemination (TAI), and to determine
      if cryopreservation by vitrification could improve survival of IVP embryos
      transferred to dairy cattle under heat stress conditions. For vitrified embryos
      (TET-V), a three-step pre-equilibration procedure was used to vitrify excellent
      and good quality Day 7 IVP Holstein blastocysts. For fresh IVP embryos (TET-F),
      Holstein oocytes were matured and fertilized; resultant embryos were cultured in
      modified KSOM for 7 days using the same method as for production of vitrified
      embryos. Excellent and good quality blastocysts on Day 7 were transported to the
      cooperating dairy in a portable incubator. Nonpregnant, lactating Holsteins (n =
      155) were treated with GnRH (100 microg, i.m., Day 0), followed 7 days later by
      prostaglandin F2alpha (PGF2alpha, 25 mg, i.m.) and GnRH (100 microg) on Day 9.
      Cows in the TAI treatment (n = 68) were inseminated the next day (Day 10) with
      semen from a single bull that also was used to produce embryos. Cows in the other
      treatments (n = 33 for TET-F; n = 54 for TET-V) received an embryo on Day 17
      (i.e. Day 7 after anticipated ovulation and Day 8 after second GnRH treatment).
      The proportion of cows that responded to synchronization based on plasma
      progesterone concentrations on Day 10 and Day 17 was 67.7%. Pregnancy rate for
      all cows on Day 45 was higher (P < 0.05) in the TET-F treatment than for the TAI
      and TET-V treatments (19.0 +/- 5.0,6.2 +/- 3.6, and 6.5 +/- 4.1%). For cows
      responding to synchronization, pregnancy rate was also higher (P < 0.05) for TET
      F than for other treatments (26.7 +/- 6.4, 5.0 +/- 4.3, and 7.4 +/- 4.7%). In the
      TET-F treatment group, cows producing more milk had lower (P < 0.05) pregnancy
      rates than cows producing less milk. In conclusion, ET of fresh IVP embryos can
      improve pregnancy rate under heat stress conditions, but pregnancy rate following
      transfer of vitrified embryos was no better than that following TAI.

PMID- 12182359
TI  - Effects of deslorelin or hCG administration on reproductive performance in first
      postpartum estrus mares.
AB  - A tendency for deslorelin implants to suppress subsequent follicular growth and
      delay return to estrus following induced ovulation has been documented in
      nonlactating mares. To investigate this phenomenon in lactating mares, 22
      broodmares in southeast Texas were administered either deslorelin or hCG to
      induce ovulation in the first postpartum estrus during February and March 2001.
      Mares were teased daily and examined twice weekly (Tuesdays and Thursdays) by
      transrectal ultrasonography. When a follicle >35 mm diameter was detected on
      Tuesday, mares were treated with either 2,500 U hCG administered intravenously or
      with one implant (2.1 mg) deslorelin administered subcutaneously. Mares were bred
      every other day until ovulation was detected or until they ceased behavioral
      estrus, and were examined 16 days after treatment to detect pregnancy. Follicular
      measurements were recorded for all mares during each examination, and
      interestrous intervals were recorded for mares not becoming pregnant. Treatment
      of mares with either hCG or deslorelin resulted in similar ovulatory responses
      and pregnancy rates. Deslorelin-treated mares had fewer ovarian follicles >20 mm
      in diameter 16 days after treatment than hCG-treated mares (P < 0.01).
      Interestrous intervals for mares failing to become pregnant on foal heat breeding
      were prolonged in deslorelin-treated compared to hCG-treated mares (P < 0.01).
      Date of treatment was negatively correlated with length of the interestrous
      interval in deslorelin-treated mares (P < 0.01), but was not correlated with
      length of interestrous interval in hCG-treated mares (P > 0.10). All mares
      failing to become pregnant from foal heat breedings became pregnant from later
      breedings, but the parturition to conception interval was prolonged in deslorelin
      treated compared to hCG-treated mares that did not become pregnant on foal heat
      (P < 0.01).

PMID- 12182361
TI  - An effective method for freezing White Italian gander semen.
AB  - Efficiency of freezing method, worked out for the White Italian gander semen was
      evaluated by comparing motility, morphology and fertilizing ability of
      spermatozoa in fresh and frozen-thawed semen. A part of pooled semen, collected
      from 25 White Italian ganders by dorso-abdominal massage was used immediately for
      artificial insemination of 10 geese (the control group) with a dose of 80 microl.
      This insemination was performed six times at weekly intervals. The remainder of
      the semen was diluted 1:0.5 (v/v) with EK diluent, equilibrated for 15 min at +4
      degrees C, mixed with 6% (v/v) of dimethylformamide (DMF) and frozen to -140
      degrees C at a rate of 60 degrees C/min. Frozen semen was thawed in a 60 degrees
      C water-bath and inseminated twice weekly in a dose of 100 microl (10 females of
      the experimental group, 12 inseminations were made). The freezing process
      affected spermatozoa motility and morphology, but had no effect on their
      fertilizing ability. Positive movement was observed in 50-60% of the spermatozoa
      in fresh semen and about 40% of the frozen-thawed cells. The average percentage
      of total live and live normal spermatozoa decreased due to freezing from 92.2 to
      68.4% and from 34.7 to 14.1%, respectively. After the fresh semen insemination
      with average 12 million of the live normal spermatozoa per week average fertility
      was 88.24%; hatchability of set eggs was 80.88% and hatchability of fertile eggs
      was 91.67%. For frozen-thawed semen inseminated with average 9.5 million of the
      undamaged spermatozoa per week, the average fertility and hatchability rate was
      83.78, 73.87, and 88.17%, respectively. Fecundity rates obtained after
      insemination with the frozen-thawed gander semen allow for the application of the
      freezing technique into breeding practice, in place of natural mating or to
      assist natural mating in periods of lowered fertility level.

PMID- 12182362
TI  - Effects of hemicastration and castration on foam production and its relationship
      with fertility in male Japanese quail.
AB  - Healthy heavy body weight strain of adult male Japanese quail (Coturnix coturnix
      Japonica) of the same age were used in this study to observe the effect of
      hemicastration and castration on the frequency of foam discharges from cloacal
      gland and other related parameters. The quails were housed in individual cages
      and divided into four groups: control (intact birds), sham-operated control
      (intact birds with incision), hemicastrated, and castrated groups of birds.
      Hemicastration and castration were carried out surgically at 10 and 13 weeks of
      age, respectively. Subsequently, 3 weeks after castration birds were examined for
      different parameters. Hemicastration caused a significant (P < 0.05) drop in the
      foam discharge frequency, weight of the foam, and the level of testosterone in
      the plasma, whereas in castrated group these variables were observed nil or
      negligible as compared to both of the controls. A suppressive effect of
      hemicastration was also noticed on the body weight, area of the cloacal gland, as
      well as percent fertility. Castration induced the drastic regression of the
      cloacal gland and a significant reduction (P < 0.05) of the body weight was also
      noted as compared to other groups. Frequencies of foam discharges were twice the
      number in daytime (06:00-18:00 h) than night, irrespective of the groups. In
      another study, the effect of characteristics of foam or foam glands on fertility
      was examined in 77 male birds paired with females. Several characteristics of
      foam and foam glands were examined for infertility, such as light yellow foam,
      dark yellow foam, smaller area of foam gland (below 225 mm2), hardness of foam
      gland and certain unknown factors that contributed 0.23, 0.68, 5.23, 2.27 and
      3.64% infertility, respectively. An overall 12.1% birds were found to be
      infertile. This data indicated that smaller sizes of foam glands might reflect
      the poorest fertilizing ability of the male birds. From this study, it may be
      concluded that the cloacal gland may be considered as an external indicator of
      testicular function of the birds. Characteristics of the cloacal gland or foam or
      both may be used as a simple and effective tool to predict the fertilizing
      ability of an individual male in view of the very small semen ejaculate that is
      very difficult to collect and evaluate for fertility.

PMID- 12182363
TI  - Seasonal variations in testicular consistency, scrotal circumference and
      spermiogramme parameters of extensively reared Brahman (Bos indicus) bulls in the
      tropics.
AB  - Twenty-five mature Brahman (Bos indicus) extensively reared breeding bulls were
      clinically examined and electroejaculated at monthly intervals for 13 months to
      study if testicular consistency (TC), scrotal circumference (SC), sperm motility
      and morphology show seasonal variation under tropical conditions. Changes in SC
      were positively related to body condition (BC) (beta = 0.7 cm, P < 0.001) and age
      (P < 0.01). These changes were, however, not associated with deviations in TC,
      sperm motility or morphology (P > 0.05). Sperm motility was higher in samples
      collected during the breeding season than in samples collected at other times (62
      versus 52%, LSM, P < 0.01). The frequency of bent tails with cytoplasmic droplet
      entrapped fluctuated between monthly ejaculates, (LSM range 3-21%, P < 0.05).
      However, there was no relationship between these fluctuations and environmental
      temperature, rainfall or changes in BC, TC or SC of the bulls (P > 0.05). Other
      sperm abnormalities did not change significantly during the study period. The
      absence of a relationship between any of the climatic variables studied and SC,
      TC and sperm motility or morphology, respectively, indicates that temperature is
      not a main factor influencing reproductive performance in Brahman bulls in the
      tropics. On the contrary, the changes found in BC followed by variations in SC
      suggest that nutrition may be a major factor affecting seasonal variations in
      male reproductive parameters, especially testicular size, in these sires.

PMID- 12182364
TI  - Plasma progesterone profiles and factors affecting embryo-fetal mortality
      following embryo transfer in dairy cattle.
AB  - The relationship between plasma progesterone (P4) levels and embryo survival, and
      the value of P4 profiles for the selection of cattle embryo transfer recipients
      is still a matter of controversy. This study reports a comparison between
      lactating cows and heifers (n = 407) from a single dairy herd, after transfer of
      either fresh or frozen-thawed good quality embryos, of their ability to sustain
      embryo-fetal development to term. Plasma P4 concentrations on the day of estrus
      (Day 0 = D0), Day 4, Day 7 and on Day 21 were measured and related to embryo
      survival. Plasma P4 levels on Days 0, 4 and 7 were similar in recipients later
      found pregnant or open. Plasma P4 levels on Day 7 were significantly higher (P <
      0.01) in heifers than in cows, but they were similar in pregnant and nonpregnant
      heifers and in pregnant and nonpregnant cows. Pregnancy rates for fresh and
      frozen-thawed embryos were higher in heifers than in cows, but the differences
      did not reach significance. However, the overall late embryonic mortality was
      significantly higher (P < 0.01) and the calving rate for frozen-thawed embryos
      was significantly lower (P < 0.05) in cows than in heifers. As expected, plasma
      P4 on Day 21 was significantly higher (P < 0.001) in pregnant than in nonpregnant
      recipients, but there was no difference between pregnant cows and pregnant
      heifers. Plasma P4 levels on Day 7 of recipients presumed pregnant on Day 21 and
      later found pregnant or nonpregnant were similar, but plasma P4 levels on Day 21
      were significantly higher (P < 0.001) in pregnant than in nonpregnant recipients.
      The results of this study suggest that plasma P4 levels until the day of
      transfer, except for the rejection of recipients with abnormal luteal function,
      are of limited practical use for embryo transfer recipient selection. However, in
      lactating cows low plasma P4 values on Day 7 might negatively affect embryo
      survival, while in heifers this effect is not noticeable. Lactating cows are more
      prone to embryo loss than heifers, especially in the case of frozen-thawed
      embryos; this is associated with a lower competence of the corpus luteum at Day
      7.

PMID- 12182365
TI  - Ultrasonographic appearance of tissue is a better indicator of CL function than
      CL diameter measurement in dairy cows.
AB  - In this study, the ovaries of 99 randomly selected Friesian cows were examined by
      ultrasonography measuring the diameter and evaluating the appearance of corpora
      lutea (CLs) in order to assess the most reliable method for their functional
      classification. Concurrently, blood samples were taken and analyzed for plasma
      progesterone (P4) concentration. On the basis of the ultrasonographic measurement
      of the diameter of the CL, three groups were established: (A) CL not detected (n
      = 30), (B) CL psi < 20 mm (n = 22), and (C) CL psi > or = 20mm (n = 47). On the
      basis of the ultrasonographic appearance, three different groups were
      established: (A) CL not detected (n = 30), (B) evolving CL (n = 25), and (C) mid
      cycle CL (n = 44). On the basis of the P4 values, CLs were functionally
      classified in the following three groups: (A) CL not detected when plasma P4 was
      lower than 1 ng/ml (n = 27), (B) evolving CL when plasma P4 was between 1 and 4
      ng/ml inclusive (n = 29), and (C) mid-cycle CL when plasma P4 was more than 4
      ng/ml (n = 43). The degree of agreement between plasma P4 concentrations and
      either ultrasonographic classification (diameter or appearance) was highly
      significant (P < 0.001). However, the results of the present study suggest that
      for the evaluation of functional classification of the CL in cows
      ultrasonographic appearance is more reliable than the evaluation of the diameter.

PMID- 12182366
TI  - Vitrification and rapid freezing of rabbit fetal tissues and skin samples from
      rabbits and pigs.
AB  - Vitrification (3.58 M EG and 2.82 M DMSO in PBS with 20% FCS) and rapid-freezing
      (0.25 M sucrose, 2.25 M EG, and 2.25 M DMSO in PBS with 20% FCS) procedures were
      assayed to cryopreserve rabbit tissue samples from 12-day fetuses, and skin
      samples from live born pups and adult rabbits. These methods were also assayed to
      cryopreserve pig skin samples obtained from abattoir animals. The ability of
      rabbit tissue samples to attach and colonize the substratum by cell proliferation
      was not affected by the assayed cryopreservation procedures, regardless of
      specimen age. In porcines, sample attachment and cell proliferation capability of
      primary cultures were not affected by applied cryopreservation procedures. Almost
      all primary cultures from cryopreserved skin samples reached confluency (from 92
      to 100%). Results reported here allow us to establish in both species, rabbit and
      pig, a cryobank of skin samples from adult specimens classified as outliers for
      longevity (in rabbits) and prolificacy (in pigs).

PMID- 12182367
TI  - Comparison of the effects of using standard and simple portable CO2 incubators on
      the in vitro developmental competence of bovine embryos reconstituted by somatic
      cell nuclear transfer.
AB  - In an attempt to determine the cultural factors that would improve cloning
      efficiency, we compared the effects of two incubation systems-a simple portable
      system and a standard CO2 incubator-on the production of bovine embryos by
      electrofusion of quiescent fetal fibroblast nuclei to enucleated oocytes matured
      in vitro. While the temperature (38.5 degrees C) and CO2 concentration (5%) were
      similar in both systems, the portable incubator operated in a vacuum of 300 mmHg
      and at an O2 level of 8-10%, which is lower than the standard. Although there
      were no significant differences between the two systems in terms of in vitro
      oocyte maturation (MII stage), fusion rates, and the number of cells in Day 7
      blastocysts, significantly higher proportions of nuclear-transferred oocytes
      cleaved (P < 0.05) and developed to the blastocyst stage (P < 0.01) in the
      portable incubator (70.5 +/- 0.6 and 36.1 +/- 1.4%, respectively) than in the
      standard incubator (64.1 +/- 3.2 and 23.5 +/- 1.4%, respectively). Following the
      transfer of six blastocysts from the portable incubator group to three
      recipients, survival rates on Days 60, 90, and 120 were 100, 66.7 and 33.3%,
      respectively. This relatively high early embryonic loss may be associated with
      multiple pregnancy complications or other abnormalities of placentation
      frequently observed in cloned embryos. Further studies using this portable
      incubator system are needed to determine the optimum levels of O2, CO2, and air
      pressure.

PMID- 12182368
TI  - Plasma membrane and acrosomal integrity in bovine spermatozoa with the knobbed
      acrosome defect.
AB  - Previous studies have shown that bovine spermatozoa with the knobbed acrosome
      defect have a reduced ability to bind to and penetrate the bovine zona pellucida.
      Cryopreserved spermatozoa from a normal control bull (N) and two bulls with the
      knobbed acrosome defect (K1 and K2) were subjected to a hypoosmotic swelling test
      (HOST) to evaluate the functional integrity of the plasma membrane. A
      capacitation assay and a calcium ionophore challenge test was used to determine
      the ability of spermatozoa to undergo capacitation and acrosome reaction (AR),
      respectively. The mean percentage of spermatozoa responding to the HOST was
      significantly higher for Bull N (68.8 +/- 2.4) than for Bulls K1 (36.1 +/- 4.6)
      and K2 (40.2 +/- 4.7). The mean percentage of capacitated spermatozoa (54.0 +/-
      1.8) was significantly higher for the treatment group (incubation in capacitating
      medium) for Bull N than that of the negative control group (29.5 +/- 1.8).
      However, there was no difference between the treatment and the negative control
      groups of the bulls with the knobbed spermatozoa (36.5 +/- 1.4 and 27.1 +/- 3.0
      for Bull K1 and 47.5 +/- 3.8 and 35.2 +/- 6.6 for Bull K2, respectively).
      Although the mean percentage of acrosome-reacted spermatozoa (60.7 +/- 1.3) was
      higher for the treatment group (receiving calcium ionophore) for Bull N than that
      of the negative control (29.5 +/- 1.3), there was no difference between the
      treatment and the negative control groups for the bulls with the knobbed
      spermatozoa (47.8 +/- 3.3 and 49.3 +/- 5.0 for Bull K1 and 58.8 +/- 10 and 59.5
      +/- 9.7 for Bull K2, respectively). A positive correlation existed between the
      proportion of spermatozoa that did not respond to the HOST and that undergoing a
      spontaneous AR. Results suggest that spermatozoa with the knobbed acrosome defect
      have impaired plasma membrane function which predisposes them to premature
      capacitation and spontaneous AR on incubation after thawing.

PMID- 12182369
TI  - Differences in sperm migration through cervical mucus in vitro relates to sperm
      colonization of the oviduct and fertilizing ability in goats.
AB  - Sperm migration in estrous cervical mucus can be used to measure the ability of
      spermatozoa to migrate through the genital tract. The relationship of this test
      with the sperm colonization of the isthmus, and its impact on fertility has not
      been evaluated in goats. Our objectives were to determine the differences among
      spermatozoa of different bucks in their ability to penetrate homologous cervical
      mucus in vitro and to determine the relationship between sperm displacement
      through cervical mucus and the ability of spermatozoa to colonize the oviduct and
      penetrate IVM oocytes, in vivo. Sperm migration in cervical mucus was assessed in
      flat capillary tubes with a phase contrast microscope. In the first experiment,
      fresh semen was used to establish differences between males in the ability of
      their spermatozoa to migrate in cervical mucus. In the second experiment, goats
      in estrus were inseminated with fresh spermatozoa from males with significant
      differences in mucus migration ability, and sperm numbers were evaluated at the
      UTJ. In the third experiment, the fertilization efficiency of IVM oocytes
      transferred to the oviduct of estrous females inseminated with semen from the
      same males as earlier, was used to assess the relationship between the mucus
      migration test and the in vivo fertilization performance of their spermatozoa.
      Spermatozoa from different males varies significantly in sperm migration
      efficiency in cervical mucus (15.5a +/- 1.2; 14.9a +/- 1.4; 17.5ab +/- 1.2;
      17.0ab +/- 1.5; 19.7b +/- 1.2; 20.1b +/- 1.4 mm; media +/- S.E.M. for males A-F,
      respectively, P < 0.05). Spermatozoa from males with different mucus migration
      efficiency values produced different sperm populations at the oviduct reservoir
      of inseminated females (1,233 +/- 92.3 versus 28.8 +/- 17.0 spermatozoa of males
      with high and low relative migration efficiency, respectively, P < 0.02).
      Spermatozoa from males with different mucus migration efficiency values have
      different fertilization rates of IVM oocytes transferred to oviduct (47/96
      (49.0%) versus 25/91 (27.5%) for males with high and low relative migration
      efficiency, respectively, P < 0.05). Cumulative results suggest that sperm
      migration in cervical mucus is related to the ability of spermatozoa to colonize
      the oviduct and to fertilize matured oocytes in vivo.

PMID- 12182370
TI  - Interventional study to evaluate the impact of an alcohol-based hand gel in
      improving hand hygiene compliance.
AB  - OBJECTIVE: To evaluate the effects of the introduction of an alcohol-based hand
      gel and multifaceted quality improvement (QI) interventions on hand hygiene (HH)
      compliance. DESIGN: Interventional, randomized cohort study with four study
      phases (baseline; limited intervention in two units; full intervention in three
      units; washout phase), performed in three intensive care units at a pediatric
      referral hospital. METHODS: During 724 thirty-minute daytime monitoring sessions,
      a nonidentified observer witnessed 12,216 opportunities for HH and recorded
      compliance. INTERVENTIONS: Introduction of an alcohol-based hand gel;
      multifaceted QI interventions (educational program, opinion leaders, performance
      feedback). RESULTS: Baseline compliance decreased after the first 2 weeks of
      observation from 42.5% to 28.2% (presumably because of waning of a Hawthorne
      effect), further decreased to 23.3% in the limited intervention phase and
      increased to 35.1% after the introduction of a hand gel with QI support in all
      three units (P < 0.001). The rise in compliance persisted in the last phase
      (compliance, 37.2%); however, a gradual decline was observed during the final
      weeks. Except for the limited intervention phase, compliance achieved through
      standard handwashing and glove use remained stable around 20 and 10%,
      respectively, whereas compliance achieved through gel use increased to 8% (P <
      0.001). After adjusting for confounding, implementation of the hand gel with QI
      support remained significantly associated with compliance (odds ratio, 1.6; 95%
      confidence interval, 1.4 to 1.8). In a final survey completed by 62 staff
      members, satisfaction with the hand gel was modest (45%). CONCLUSIONS: We noted a
      statistically significant, modest improvement in compliance after introduction of
      an alcohol-based hand gel with multifaceted QI support. When appropriately
      implemented, alcohol-based HH may be effective in improving compliance.

PMID- 12182371
TI  - Commentary: Waterless hand hygiene--if there's a will, there's a way.

PMID- 12182372
TI  - Childhood vaccinations and risk of asthma.
AB  - BACKGROUND: A few previous studies have suggested that childhood vaccines,
      particularly whole cell pertussis vaccine, may increase the risk of asthma. We
      evaluated the suggested association between childhood vaccinations and risk of
      asthma. METHODS: Cohort study involving 167,240 children who were enrolled in 4
      large health maintenance organizations during 1991 to 1997, with follow-up from
      birth until at least 18 months to a maximum of 6 years of age. Vaccinations were
      ascertained through computerized immunization tracking systems, and onset of
      asthma was identified through computerized data on medical care encounters and
      medication dispensings. RESULTS: In the study 18,407 children (11.0%) developed
      asthma, with a median age at onset of 11 months. The relative risks (95%
      confidence intervals) of asthma were: 0.92 (0.83 to 1.02) for diphtheria, tetanus
      and whole cell pertussis vaccine; 1.09 (0.9 to 1.23) for oral polio vaccine; 0.97
      (0.91 to 1.04) for measles, mumps and rubella (MMR) vaccine; 1.18 (1.02 to 1.36)
      for Haemophilus influenzae type b (Hib); and 1.20 (1.13 to 1.27) for hepatitis B
      vaccine. The Hib result was not consistent across health maintenance
      organizations. In a subanalysis restricted to children who had at least 2 medical
      care encounters during their first year, the relative risks decreased to 1.07
      (0.71 to 1.60) for Hib and 1.09 (0.88 to 1.34) for hepatitis B vaccine.
      CONCLUSION: There is no association between diphtheria, tetanus and whole cell
      pertussis vaccine, oral polio vaccine or measles, mumps and rubella vaccine and
      the risk of asthma. The weak associations for Hib and hepatitis B vaccines seem
      to be at least partially accounted for by health care utilization or information
      bias.

PMID- 12182373
TI  - Variations in central venous catheter-related infection risks among Canadian
      neonatal intensive care units.
AB  - BACKGROUND: The objective of this study was to examine central venous catheter
      (CVC)-related nosocomial blood stream infection risks of umbilical venous,
      percutaneous and Broviac catheters, as well as variations in CVC use and CVC
      related risk for nosocomial blood stream infection in the neonatal intensive care
      unit (NICU). METHODS: A cohort study was performed based on 19,507 infants
      admitted to 17 NICUs in the Canadian Neonatal Network from January, 1996, through
      October, 1997. Information on these subjects was prospectively collected by
      trained abstractors. Incidence of infection was measured as infection episodes
      per 1000 patient days. The risk ratio (RR) of CVC use for nosocomial blood stream
      infection was calculated as the infection rate during catheter days divided by
      the infection rate during noncatheter days. Using a Poisson regression model we
      examined the adjusted RR of CVC use for nosocomial blood stream infection,
      controlling for patient characteristics and illness severity at admission.
      Interinstitutional variations in CVC-related infection risks were examined by
      stratified analyses. RESULTS: CVC were used in 22.5% of patients. The incidence
      of nosocomial blood stream infection was 2.9 per 1000 noncatheter days, 7.2 per
      1000 umbilical venous catheter days, 13.1 per 1000 percutaneous catheter days and
      12.1 per 1000 Broviac catheter days. The RR for nosocomial blood stream
      infection, adjusted for differences in patient characteristics and admission
      illness severity, was 2.5 for umbilical venous catheter, 4.6 for percutaneous
      catheter and 4.3 for Broviac catheter (P < 0.05). There were significant (P <
      0.05) risk-adjusted variations in CVC-related infection risks among NICUs.
      CONCLUSIONS: CVC use increased the risk of nosocomial blood stream infection. The
      risk of nosocomial blood stream infection in percutaneous and Broviac catheters
      was 70 to 80% higher than in umbilical venous catheters. There was significant
      variation in CVC-related infection risks among Canadian NICUs.

PMID- 12182374
TI  - Palivizumab prophylaxis for respiratory syncytial virus in Canada: utilization
      and outcomes.
AB  - OBJECTIVE: To provide information on the use and outcomes of palivizumab
      prophylaxis in children at high risk of serious respiratory syncytial virus (RSV)
      infection. DESIGN: Observational, prospective, longitudinal, multicenter study.
      SETTING: Eighteen hospitals and pediatric clinics located in six provinces across
      Canada. PATIENTS: Infants enrolled in the palivizumab Special Access Programme of
      Canada's Therapeutic Products Programme throughout the 1999 to 2000 RSV season.
      Most were premature infants born at < or = 32 weeks of gestation and/or had
      bronchopulmonary dysplasia. METHODS AND MAIN OUTCOME MEASURES: Neonatal and
      demographic data were recorded for each subject. The parent/caregiver was
      contacted on a monthly basis until the end of the RSV season to obtain
      information on palivizumab utilization and compliance as well as incidence and
      severity of respiratory infections. RESULTS: There were 444 evaluable subjects
      who each received 1 to 7 injections of palivizumab for a total of 1702 doses from
      September 1999 to April 2000. Most subjects received 5 injections with high
      compliance. Prophylaxis was discontinued in 2% of children. There were 116
      clinical events or hospitalizations involving respiratory tract infections
      reported in 91 children. Eighty-six of these were managed in an outpatient
      setting, and 30 required hospitalization. The estimated incidence of
      hospitalization for RSV-positive lower respiratory tract infections (LRTIs) was
      2.4%. Hospitalization for RSV LRTI occurred more often in children with
      bronchopulmonary dysplasia (6.0%) than in those with prematurity only (1.6%).
      CONCLUSIONS: This study demonstrates that prophylaxis with palivizumab during the
      RSV season was associated with a low rate of hospitalization for RSV-positive
      LRTIs. Palivizumab was well-tolerated, and compliance was high. The findings
      confirm the results of the major randomized clinical trial of palivizumab and
      demonstrate the safety and effectiveness of RSV prophylaxis.

PMID- 12182375
TI  - Early multitherapy including a protease inhibitor for human immunodeficiency
      virus type 1-infected infants.
AB  - BACKGROUND: To assess tolerance and efficacy of early multitherapy including a
      protease inhibitor for infants perinatally infected with HIV. METHODS:
      Observational study of tolerance and clinical and immunovirologic evolution in
      HIV-infected infants treated before the age of 1 year in the French Perinatal
      Study. RESULTS: Thirty-one infants were included. The median age was 3.7 months
      at initiation of multitherapy. Clinical stage was C (n = 8), B (n = 5) or A/N (n
      = 18). The median HIV RNA viral load was 5.8 log copies/ml, and the median CD4
      cell percentage was 29%. Median follow-up of treatment was 27 months. Of 31
      infants 15 experienced mild to moderate adverse events. No infant had clinical or
      immunologic progression. The median change in viral load was -2.7 log copies/ml
      after 3 months, -2.0 log after 12 months and -1.7 log after 24 months of
      treatment. The proportion of infants with a viral load below 500 copies/ml
      decreased from 53% at 6 months to 18% at 24 months of treatment. The virologic
      response was not correlated with viral load at baseline. However, the slope of
      the viral load decrease during the first month of treatment was predictive of the
      virologic response at 3 and 6 months. Fourteen infants with a viral load of >500
      copies/ml after 6 months of treatment displayed viruses with antiretroviral
      resistance mutations in reverse transcriptase and/or protease genes. CONCLUSIONS:
      Despite the absence of clinical or immunologic progression, the high frequency of
      virologic failure associated with genotypic resistance reveals the difficulties
      associated with implementing antiretroviral multitherapy in infants. Suboptimal
      doses of protease inhibitor could be a factor contributing to treatment failure.

PMID- 12182376
TI  - Tendon or joint disorders in children after treatment with fluoroquinolones or
      azithromycin.
AB  - BACKGROUND: Fluoroquinolones (FQs) have been infrequently used in children,
      largely because of concern that these agents can cause lesions of the cartilage
      in juvenile animals. However, the relevance of this laboratory observation to
      children treated with FQs is unknown. A retrospective, observational study was
      conducted to assess the incidence and relative risk of tendon or joint disorders
      (TJDs) that occur after use of selected FQs compared with azithromycin (AZ), a
      drug with no known effect on cartilage or tendons in humans or animals. METHODS:
      An automated database was searched to identify patients younger than 19 years who
      had been prescribed ofloxacin (OFX), levofloxacin, ciprofloxacin (CPX), or AZ.
      Potential cases of TJD occurring within 60 days of a prescription of one of the
      study drugs were identified based on assignment of a claims diagnosis consistent
      with a TJD within this period. Verified cases were identified by a blinded review
      of abstracts of medical records from subjects identified as potential cases.
      RESULTS: The incidence of verified TJD was 0.82% for OFX (13 of 1593) and CPX (37
      of 4531) and was 0.78% for AZ (118 of 15,073). The relative risk of TJD for OFX
      and CPX compared with AZ was 1.04 (95% confidence interval, 0.55 to 1.84) and
      1.04 (95% confidence interval, 0.72 to 1.51), respectively. The distributions of
      claims diagnoses and time to onset of TJD were comparable for all groups. The
      most frequently reported category of TJD involved the joint followed by tendon,
      cartilage and gait disorder. CONCLUSIONS: In this observational study involving
      more than 6000 FQ-treated children, the incidence of TJD associated with selected
      FQ use in children was <1% and was comparable with that of the reference group,
      children treated with AZ.

PMID- 12182377
TI  - Clindamycin treatment of methicillin-resistant Staphylococcus aureus infections
      in children.
AB  - BACKGROUND: Methicillin-resistant Staphylococcus aureus (MRSA) with a narrower
      antibiotic resistance pattern have emerged. There is a risk for the appearance of
      resistance during clindamycin therapy of erythromycin-resistant MRSA infections
      because of the linked resistance mechanisms. METHODS: We analyzed clindamycin
      susceptible MRSA organisms from children (1987 to 2000) along with clinical data.
      Antibiotic susceptibilities of organisms were tested, pulsed field gel
      electrophoresis (PFGE) was done and the linked resistance mechanism was detected
      by the D test. RESULTS: An average of 11 clindamycin-susceptible MRSA per year
      were obtained from children since 1993. Of 88 isolates 33 (38%) were erythromycin
      resistant. The latter were less often community-acquired (45% vs. 69%), more
      often from infants <1 month of age (24% vs. 4%) and less likely to be in the
      community acquisition-associated PFGE Group 1 (62% vs. 87%) than those that were
      susceptible. The D test was positive in 31 of 33 erythromycin-resistant isolates.
      A 9-month-old boy with pneumonia/empyema caused by a clindamycin-susceptible,
      erythromycin-resistant, D test-positive MRSA developed a PFGE-identical
      clindamycin-resistant isolate and clinical relapse during clindamycin treatment.
      In contrast a 12-year-old girl with abscesses caused by a similar MRSA developed
      another abscess after clindamycin therapy, but the organism was unchanged in
      susceptibility. CONCLUSIONS: Erythromycin resistance was present in 38% of
      clindamycin-susceptible MRSA in children, and clindamycin resistance was detected
      during treatment in one child. Clindamycin remains a treatment option if the
      clinician is notified of the risk by the microbiology laboratory and the clinical
      situation is suitable.

PMID- 12182378
TI  - Antibody persistence in five-year-old children who received a pentavalent
      combination vaccine in infancy.
AB  - BACKGROUND: Antibody persistence was studied in 5.5-year-old Swedish children who
      in infancy completed a vaccine trial of a combined diphtheria toxoid, tetanus
      toxoid, acellular pertussis, inactivated polio and Haemophilus influenzae type b
      conjugate vaccine. Three priming doses at ages 2-4-6 months induced higher
      geometric mean concentrations of antibodies for all antigens than did two doses
      at 3-5 months, but there were no differences in proportions with protective
      antibody concentrations. After the booster dose administered at 13 or 12 months
      of age, respectively, there were no differences in concentrations or proportions
      between the groups. METHODS: In the present follow-up serum samples from 180 of
      the 228 vaccinees, 88 from the 4-dose and 92 from the 3-dose group, were 4.5
      years later again tested for antibodies. RESULTS: The two groups did not differ
      significantly in antibody concentrations or proportions with antibodies above
      protective or other defined levels, with the exception of poliovirus type 3 (P <
      or = 0.01). In all 89% had > or = 0.01 IU/ml antibodies against diphtheria by
      enzyme-linked immunosorbent assay and 76% by the Vero cell neutralization test,
      93% had > or = 0.01 IU/ml antibodies against tetanus, 96 to 99% had detectable
      antibodies against the polioviruses and 97% had > or = 0.15 microg/ml H.
      influenzae type b antibodies. As for pertussis only 44% had detectable antibodies
      against pertussis toxoid by enzyme-linked immunosorbent assay but 99% by Chinese
      hamster ovary cell neutralization test, and 94% had detectable antibodies against
      filamentous hemagglutinin. CONCLUSION: We found the persistence of antibodies
      satisfactory, with no clinically relevant differences in antibody concentrations
      demonstrated between children vaccinated according to a three dose or a four dose
      schedule in infancy.

PMID- 12182379
TI  - Instituting a routine varicella vaccination program in Canada: an economic
      evaluation.
AB  - BACKGROUND: After licensing of a varicella vaccine in Canada in 1998, Health
      Canada commissioned a study to evaluate options for a vaccination program. The
      evaluation of a program of vaccination of 12-month-old children, with and without
      a catch-up program for susceptible 12-year-olds, is presented here. METHODS: An
      economic model was developed simulating the expected experience, with and without
      vaccination, of cohorts of children susceptible to varicella. The cohorts were
      simulated for 70 years, and infection and complication rates were calculated
      along with the attendant costs, with an assumed vaccine cost of $60. RESULTS:
      With an 85% coverage rate vaccination is expected to reduce the number of
      chickenpox cases by approximately two-thirds and varicella-related complications
      by up to 75%. The overall costs of varicella are expected to drop by >$4 million
      (1998 Canadian dollars) per 100,000 eligible vaccinees, but costs to the health
      care system are expected to increase by >$2 million. From the health care system
      perspective, vaccination would cost approximately $42 per discounted case
      avoided. INTERPRETATION: Routine varicella vaccination would likely substantially
      reduce the overall costs of managing chickenpox but would result in an increase
      in health care expenditures. These findings are consistent with evaluations in
      other countries.

PMID- 12182380
TI  - Immune response to octavalent diphtheria- and tetanus-conjugated pneumococcal
      vaccines is serotype- and carrier-specific: the choice for a mixed carrier
      vaccine.
AB  - BACKGROUND: Development of protein-conjugated pneumococcal vaccines for infants
      has led to formulations that are immunogenic in the age group at highest risk for
      pneumococcal diseases. This study focuses on the search for an optimal
      formulation. METHODS: In a randomized trial Icelandic infants (n = 160) were
      immunized at age 3, 4 and 6 months with one of two octavalent pneumococcal
      conjugate vaccines (serotypes 3, 4, 6B, 9V, 14, 18C, 19F and 23F conjugated to
      diphtheria toxoid (PncD) or tetanus protein (PncT) followed with a booster of
      either the same conjugate or 23-valent polysaccharide vaccine at 13 months.
      Safety data were collected after each vaccination, and IgG responses (enzyme
      linked immunosorbent assay) were measured at 3, 4, 6, 7, 13 and 14 months.
      RESULTS: Both conjugates were safe and caused fewer local reactions than the
      routine vaccines (P < 0.0001). At 7 months both groups had significant IgG
      response to all serotypes. The geometric mean concentration range was 0.35 to
      4.09 and 0.65 to 3.38 microg/ml for PncD and PncT, respectively, with 88.2 to
      100% and 92.4 to 100% of subjects reaching > or = 0.15 microg/ml. The PncD gave
      better primary responses to serotypes 3, 9V and 18C, whereas PncT gave better
      response to serotype 4. Similar responses were induced to the other serotypes.
      Good booster IgG responses were obtained in all vaccine groups; 97.5 to 100% of
      subjects reached > or = 1 microg/ml. CONCLUSIONS: Both octavalent pneumococcal
      conjugates were safe and immunogenic in infants. Based on the results from this
      and similar trials, a mixed diphtheria and tetanus pneumococcal conjugate vaccine
      was designed to provide the optimal immune response to each serotype.

PMID- 12182381
TI  - Vaccination with measles, mumps and rubella vaccine and varicella vaccine:
      safety, tolerability, immunogenicity, persistence of antibody and duration of
      protection against varicella in healthy children.
AB  - BACKGROUND: Administration of M-M-R II (Measles, Mumps and Rubella Virus Vaccine,
      Live) and VARIVAX [Varicella Virus Vaccine Live (Oka/Merck)] given concomitantly
      at separate injection sites during the same office visit could increase vaccine
      compliance by reducing the number of health care visits for immunizations. We
      compared the safety and immunogenicity of M-M-R II and VARIVAX given
      concomitantly at separate sites (Group A) with administration of the two vaccines
      6 weeks apart (Group B) as well as the persistence of varicella antibody and the
      duration of protection afforded by varicella vaccine. METHODS: A total of 603
      healthy children, ages 12 months to 6 years, with no history of measles, mumps,
      rubella, varicella and zoster or vaccination against these diseases, were
      randomized to either Group A or B and were followed for clinical reactions and
      serologic responses to all four viral components. Children were enrolled from
      August through December, 1993. Subjects were followed for 5 years to evaluate
      persistence of varicella antibody and breakthrough varicella rates. We compared
      breakthrough rates to expected attack rates in unvaccinated children to produce
      estimates of vaccine efficacy. RESULTS: Both vaccine regimens were generally well
      tolerated. There were no significant differences between the groups in the rates
      of fever, injection site reactions or rashes after vaccination. Seroconversion
      rates and geometric mean titers for measles, mumps and rubella were not
      significantly different between groups. The varicella seroconversion rate and
      percentage with glycoprotein-based ELISA titers > or = 5.0 units were similar
      between the two groups (99.5 and 92.5% vs. 100 and 94.8% for Groups A and B,
      respectively), but the geometric mean titers were statistically significantly
      different (13.2 for Group A and 17.9 for Group B). Varicella antibody persistence
      rates were >98 to 100% during 6 years of follow-up in both groups. Compared with
      historical rates, varicella vaccine efficacy during 5 years was estimated to be
      90.5% (95% confidence interval, 86.2%, 95.0%) and 88.9% (95% confidence interval,
      83.7%, 93.7%) in Groups A and B, respectively. CONCLUSIONS: Administration of M-M
      R II and VARIVAX concomitantly at separate injection sites or 6 weeks apart was
      generally well-tolerated and immunogenic in healthy children 12 months to 6 years
      of age. VARIVAX administered with M-M-R II induced persistent immunity and long
      term protection against breakthrough varicella infection.

PMID- 12182382
TI  - Incomplete (atypical) Kawasaki disease.

PMID- 12182383
TI  - Human herpesviruses 6 and 7.

PMID- 12182385
TI  - Lack of association between receipt of conjugate haemophilus influenzae type B
      vaccine (HbOC) in infancy and risk of type 1 (juvenile onset) diabetes: long term
      follow-up of the HbOC efficacy trial cohort.
AB  - We evaluated the effect of infant vaccination with HbOC Haemophilus influenzae
      type b (Hib) conjugate vaccine on the risk of onset of type 1 juvenile diabetes
      later in life by examining data from a large controlled prospective Phase III
      clinical efficacy trial conducted within Northern California Kaiser Permanente
      between 1988 and 1990. The overall study population included children who were
      offered the Hib conjugate vaccine (acceptors and refusers) as well as a cohort of
      children who were systemically excluded from the trial on the basis of their
      birth date. These children are now 10 to 12 years of age. We found no evidence
      that vaccination with Hib conjugate vaccine in infancy is associated with risk of
      diabetes later in life.

PMID- 12182384
TI  - Breast milk transmission of group B streptococcal infection.
AB  - A term female infant developed late onset group B streptococcal disease on Day 12
      of life. The source of the organism appeared to be expressed maternal breast milk
      in the absence of clinical mastitis. Asymptomatic excretion of group B
      Streptococcus in breast milk may be an underrecognized cause of neonatal
      infection.

PMID- 12182386
TI  - Guillain-Barre syndrome after exanthem subitum.
AB  - A female infant developed Guillain-Barre syndrome 20 days after having exanthem
      subitum confirmed serologically as human herpesvirus 6 infection. DNA of human
      herpesvirus 6 was detected in peripheral blood mononuclear cells collected on
      admission.

PMID- 12182387
TI  - Jarisch-Herxheimer reaction associated with ciprofloxacin administration for tick
      borne relapsing fever.
AB  - A 14-year-old girl was seen at a community clinic with a chief complaint of
      abdominal pain and fevers and was treated with oral ciprofloxacin for presumed
      pyelonephritis. She became tachycardic and hypotensive after her first dose of
      antibiotic, and she developed disseminated intravascular coagulation. She was
      admitted to our hospital for presumed sepsis. Her outpatient peripheral blood
      smear was reviewed, revealing spirochetes consistent with Borrelia sp. To our
      knowledge this is the first reported case of the Jarisch-Herxheimer reaction to
      ciprofloxacin.

PMID- 12182388
TI  - Chromobacterium violaceum: a case of diarrhea in Senegal.
AB  - A 5-year-old infant with diarrhea had heavy growth of Chromobacterium violaceum
      cultured from stool. This organism is restricted geographically between latitudes
      35 degrees N and 35 degrees S. It can cause sepsis and various focal infections
      but is not a well-known cause of diarrhea.

PMID- 12182389
TI  - Cervical lymphadenitis caused by Mycobacterium lentiflavum.
AB  - We report a case of human infection caused by Mycobacterium lentiflavum and
      review the literature for infections caused by this bacterium. The patient was a
      19-month-old boy with involvement of a cervical lymph node. Surgical removal of
      the lymphadenopathy was both diagnostic and curative.

PMID- 12182390
TI  - Anaerobiospirillum succiniciproducens bacteremia in a young child.
AB  - We report a case of Anaerobiospirillum succiniciproducens bacteremia in a young
      child who had no underlying disease. The case should alert microbiologists and
      physicians to an uncommon organism that is very often resistant to antibiotics
      normally prescribed empirically for infections caused by organisms of similar
      morphology and characteristics such as Campylobacter species.

PMID- 12182391
TI  - The need for immunoglobulin for travelers who receive hepatitis A vaccine.

PMID- 12182392
TI  - Acquired multidrug-resistant tuberculosis in an immunocompetent adolescent.

PMID- 12182393
TI  - Salmonella london endogenous endophthalmitis in a healthy infant.

PMID- 12182394
TI  - Management of the febrile child without a focus of infection in the era of
      universal pneumococcal immunization.
AB  - Should strategies of management of invasive disease in the febrile child without
      focus of infection (occult bacteremia) be reconsidered in communities with
      universal immunization of infants with the conjugate vaccines for Haemophilus
      influenzae type b and Streptococcus pneumoniae (PCV7)? The incidence of occult
      bacteremia is likely to decrease with the virtual elimination of H. influenzae
      type b and vaccine serotype pneumococcal invasive diseases. The number of
      children with fever coming to physicians' offices, however, is unlikely to
      change. The challenge of distinguishing the febrile child with invasive bacterial
      disease who requires aggressive therapy from the febrile child who has a viral
      infection and requires only symptomatic therapy will persist. The bacteriology of
      invasive disease in infants and young children in 2002 will include pneumococcal
      serotypes not in PCV7; serotypes in PCV7 that occur in the unimmunized, partially
      immunized or fully immunized child (vaccine failures); Neisseria meningitidis;
      Salmonella spp., group A Streptococcus, Staphylococcus aureus and gram-negative
      enteric bacilli. Management plans published in the 1990s suggested an aggressive
      diagnostic approach to the febrile child 3 to 36 months old who was toxic or had
      a temperature of >39 degrees C. Diagnostic tests included white blood cell
      counts, cultures of blood and urine and chest radiograph and lumbar puncture as
      indicated by clinical signs and administration of parenteral ceftriaxone.
      Although PCV7 was extraordinarily effective in prevention of serotype-specific
      invasive pneumococcal disease in clinical trials, pediatricians need to know
      whether the results based on 38,000 enrollees will be maintained as millions of
      children are immunized. In addition questions about change in serotype of
      pneumococci causing invasive disease (serotype switching), herd immunity and
      durability of protection after immunization need to be answered. Until more
      experience is available to answer these questions, the febrile child without
      focus of infection should be managed without consideration of immunization with
      PCV7. Evaluation of the organism (serotype) and the host (acute and convalescent
      sera) should be undertaken for each case of invasive pneumococcal disease in this
      era of universal pneumococcal immunization.

PMID- 12182395
TI  - Management of pneumococcal meningitis.
AB  - During the past decade antibiotic resistance among Streptococcus pneumoniae
      isolates has complicated the empiric approach to and treatment of pneumococcal
      meningitis. Standard empiric therapy for suspected bacterial meningitis for
      infants and children older than 1 month of age is the combination of cefotaxime
      or ceftriaxone and vancomycin. Treatment is modified after antimicrobial
      susceptibilities are available. The optimal treatment of pneumococcal meningitis
      caused by strains with a cefotaxime/ceftriaxone MIC >2 microg/ml is unknown,
      although the addition of rifampin to the initial combination is generally
      recommended. The role of newer agents including quinolones is under
      investigation. Dexamethasone remains the only adjunctive antiinflammatory therapy
      to consider. The empiric approach to the child with suspected bacterial
      meningitis who has received the pneumococcal conjugate vaccine currently remains
      unchanged.

PMID- 12182396
TI  - Management of community-acquired pediatric pneumonia in an era of increasing
      antibiotic resistance and conjugate vaccines.
AB  - The antibiotic management of infants and children with pneumonia is based on the
      clinician's assessment of the most likely infecting pathogens, the
      susceptibilities of the infecting pathogens and the seriousness of the illness.
      The bacterial etiology of pneumonia changed significantly following the universal
      use of protein-conjugated vaccines for Haemophilus influenzae type b. Similar
      significant changes are likely to occur with universal use of protein-conjugated
      vaccines for Streptococcus pneumoniae, requiring the clinician to alter
      assumptions of the risk of invasive bacterial infection in the child who presents
      with pneumonia. New strategies are likely to require fewer ancillary tests (e.g.
      white blood cell count, C-reactive protein and blood culture) and suggest a
      decreased need for empiric antibiotic therapy. Although the majority of lower
      respiratory tract infections in children have a viral etiology and are not
      amenable to antibiotic therapy, for the seriously ill child who is thought to be
      likely to have pneumonia caused by a bacterial pathogen, recent changes in the
      susceptibility patterns of both common organisms such as S. pneumoniae and more
      unusual pulmonary pathogens such as Staphylococcus aureus have forced changes in
      the selection of both empiric and definitive antibiotic therapy. Third generation
      cephalosporins ceftriaxone and cefotaxime appear to be effective therapy for
      pneumonia caused by virtually all current isolates of S. pneumoniae. In contrast
      antibiotic regimens for life-threatening pulmonary infections in which
      Staphylococcus aureus is a suspected pathogen should include vancomycin.

PMID- 12182397
TI  - Acute otitis media in an era of increasing antimicrobial resistance and universal
      administration of pneumococcal conjugate vaccine.
AB  - The last decade has witnessed a shift in the epidemiology of acute otitis media
      (AOM) with an earlier onset of disease and a greater proportion of children with
      recurrent episodes before 1 year of age. In addition antimicrobial resistance to
      beta-lactams, macrolides and trimethoprim-sulfamethoxazole among otopathogens has
      increased significantly. Most recently universal administration of a seven valent
      pneumococcal conjugate vaccine has been endorsed by the American Academy of
      Pediatrics and the Advisory Committee on Immunization Practices. Earlier onset of
      disease and the decrease in antimicrobial susceptibility among pediatric
      respiratory bacterial pathogens is likely to increase the risk of failure among
      young children with AOM. A seven valent pneumococcal conjugate vaccine (PCV7) has
      demonstrated efficacy for prevention of serotype-specific pneumococcal otitis;
      however, increase in disease caused by nonvaccine serotypes and Haemophilus
      influenzae has been reported. With these events as the background, I have
      reviewed the strategies most likely to be successful for the treatment of AOM in
      2002.

PMID- 12182398
TI  - Rapid diagnosis in pediatric infectious diseases: the past, the present and the
      future.
AB  - The focus of rapid diagnosis of infectious diseases of children in the last
      decade has shifted from variations of the conventional laboratory techniques of
      antigen detection, microscopy and culture to that of molecular diagnosis of
      infectious agents. Pediatricians will need to be able to interpret the use,
      limitations and results of molecular diagnostic techniques as they are
      increasingly integrated into routine clinical microbiology laboratory protocols.
      PCR is the best known and most successfully implemented diagnostic molecular
      technology to date. It can detect specific infectious agents and determine their
      virulence and antimicrobial genotypes with greater speed, sensitivity and
      specificity than conventional microbiology methods. Inherent technical
      limitations of PCR are present, although they are reduced in laboratories that
      follow suitable validation and quality control procedures. Variations of PCR
      together with advances in nucleic acid amplification technology have broadened
      its diagnostic capabilities in clinical infectious disease to now rival and even
      surpass traditional methods in some situations. Automation of all components of
      PCR is now possible. The completion of the genome sequencing projects for
      significant microbial pathogens, in combination with PCR and DNA chip technology,
      will revolutionize the diagnosis and management of infectious diseases.

PMID- 12182399
TI  - Phylogeny and morphological evolution of the amblystegiaceae (Bryopsida).
AB  - To circumscribe the moss family Amblystegiaceae, we performed a broad-scale
      analysis of trnL-trnF spacer sequence data for 168 species of the Hypnales and 11
      species of the Hookeriales and additional analyses of trnL-trnF and atpB-rbcL
      (chloroplast DNA), one nuclear region, the internal transcribed spacers of 18S
      26S rDNA, and 68 morphological characters for a reduced data set of 54 species of
      Hypnales. The traditionally circumscribed Amblystegiaceae are polyphyletic and
      include the Amblystegiaceae s. str. and the Calliergonaceae fam. nov., plus
      several taxa closely related to other Hypnalean families. Generic relationships
      within the redefined Amblystegiaceae were investigated by analyzing data from the
      three DNA regions and morphology as used in the broader analysis. Reconstruction
      of morphological evolution was evaluated using maximum-parsimony and maximum
      likelihood. Numerous independent character-state transitions implied by the
      phylogeny suggest that morphological characters that have traditionally been used
      to delineate the Amblystegiaceae are homoplastic. Sporophytic traits, which are
      generally given primacy over gametophytic traits in moss classification, are more
      labile than previously thought, and many characters that are related to
      sporophyte specializations are strongly correlated with habitat conditions. The
      evolution of several gametophyte features previously thought to be reliable for
      delineating the family are also strongly correlated with habitat. These
      observations help to explain the instability of the Amblystegiaceae in previous
      taxonomic and phylogenetic analyses based on morphology.

PMID- 12182400
TI  - Molecular phylogenetics and mitochondrial genomic evolution in the chamaeleonidae
      (Reptilia, Squamata).
AB  - A phylogenetic hypothesis for the lizard family Chamaeleonidae is generated from
      1503 aligned base positions (883 parsimony-informative) of mitochondrial DNA for
      specimens representing 59 species (57 ingroup and two outgroup). Sequences are
      reported for a genomic segment encoding eight transfer RNAs, NADH dehydrogenase
      component 2 (ND2), and portions of NADH dehydrogenase component 1 (ND1) and
      cytochrome c oxidase subunit 1 (COI). Newly reported genomic rearrangements and
      duplications support the hypothesis that mitochondrial gene order and content are
      destabilized by phylogenetic loss of a functional origin for light-strand
      replication between the genes encoding tRNA(Asn) and tRNA(Cys). A novel gene
      order characterizes all sampled Brookesia except B. nasus. Brookesia nasus, the
      apparent sister taxon of a clade formed by all other Brookesia, has the ancestral
      gene order but contains a large tandem duplication. An apparently noncoding 220
      base pair insertion between the genes encoding ND2 and tRNA(Trp) is reported for
      Bradypodion tavetanum. Phylogenetic analysis identifies nine clades whose
      ancestral lineages diverged early in chamaeleonid evolutionary history: (1)
      Brookesia (possibly excluding B. nasus), (2) Chamaeleo subgenus Chamaeleo
      (excluding C. namaquensis), (3) Chamaeleo subgenus Trioceros, (4) viviparous
      Bradypodion, (5) oviparous Bradypodion, (6) genus Furcifer (except F. balteatus),
      and (7-9) three distinct clades of Calumma. Chamaeleo namaquensis, Brookesia
      nasus, Furcifer balteatus, Rhampholeon brevicaudatus, and R. spectrum represent
      ancient lineages dating to approximately the same time. Multiple independent
      losses and a possible secondary gain of horns are inferred for Trioceros.
      Viviparity has at least two separate origins in chameleons, one in Bradypodion
      and

PMID- 12182402
TI  - Phylogeny of hydradephagan water beetles inferred from 18S rRNA sequences.
AB  - Several families in the beetle suborder Adephaga have an aquatic life style and
      are commonly grouped in the "Hydradephaga," but their monophyly is contentious
      and relationships between and within these families are poorly understood. Here
      we present full-length 18S rRNA sequence for 84 species of Hydradephaga,
      including representatives of most major groups down to the tribal level, and a
      total of 68 species of the largest family, Dytiscidae. Using a direct
      optimization method for the alignment of length-variable regions, the preferred
      tree topology was obtained when the cost of gaps and the cost of nucleotide
      changes were equal, and three hypervariable regions of 18S rRNA were downweighted
      by a factor of five. Confirming recent molecular studies, the Hydradephaga were
      found to be monophyletic, indicating a single colonization of the aquatic medium.
      The most basal group within Hydradephaga is Gyrinidae, followed in a comb-like
      arrangement by families Haliplidae, Noteridae, Amphizoidae, and Hygrobiidae plus
      Dytiscidae. Under most alignment parameters, Hygrobiidae is placed amid
      Dytiscidae in an unstable position, suggesting a possible data artifact. Basal
      relationships within Dytiscidae are not well established, nor is the monophyly of
      subfamilies Hydroporinae and Colymbetinae. In contrast, relationships at the
      genus level appear generally well supported. Despite the great differences in the
      rates of change and the significant incongruence of the phylogenetic signal in
      conserved vs hypervariable regions of the 18S rRNA gene, both contribute to
      establish relationships at all taxonomic levels.

PMID- 12182401
TI  - A phylogenetic analysis of cordyliformes (Reptilia: Squamata): comparison of
      molecular and karyological data.
AB  - A karyological study and the analysis of two mitochondrial genes were conducted
      in several species of cordyliformes from Madagascar. Both studies confirmed the
      monophyly of cordyliformes. The karyological conservatism and small genetic
      distance among mitochondrial genes observed in these species are in line with the
      hypothesis that all cordyliformes should be included in a single family. The two
      studies yielded contrasting results with regard to the relationships between the
      Malagasy species and the Cordylidae and Gerrhosauridae. Nonetheless, the
      consistency between the data from mitochondrial gene analysis and those of
      taxonomic studies based on morphological characters is more in favor of an
      affinity between Malagasy Zonosaurinae and Gerrhosauridae and suggests that the
      karyological similarities between the former and the Cordylidae may be due to
      plesiomorphy. Interesting, though not conclusive, data were also obtained on
      interspecific relationships among Zono-

PMID- 12182403
TI  - Phylogenetic relationships and ancestral areas of the bustards (Gruiformes:
      Otididae), inferred from mitochondrial DNA and nuclear intron sequences.
AB  - The taxonomy of the bustards is poorly understood phylogenetically and has not
      been extensively evaluated using molecular methods. We sequenced part of the
      mitochondrial cytochrome b gene, the control region (central domain II), and an
      intron-exon crossing fragment of the nuclear chromo-helicase-DNA binding gene
      (CHD1) in 27 bustard taxa (including multiple subspecies) representing 11 genera
      and four gruiform outgroup species. Molecular datings suggest a Miocene origin
      for the family. Inferred phylogenetic relationships include the following: (i)
      the basal polytomy consists of 10 branches (mostly consistent with traditional
      genera), suggesting a rapid early radiation; (ii) sister relationships between
      several couplets of genera include Ardeotis with Neotis, Afrotis with Eupodotis
      (excluding E. rueppellii), Otis with Chlamydotis, and Houbaropsis with
      Sypheotides; (iii) the genus Eupodotis may be polyphyletic; and (iv) the
      currently delimited genera Ardeotis and Neotis do not form independent
      monophyletic lineages. Molecular evidence for the Afro-tropical origin of the
      Otididae is provided.

PMID- 12182404
TI  - Molecular phylogenetics of Iberian wall lizards (Podarcis): is Podarcis hispanica
      a species complex?
AB  - Phylogenetic relationships between species and morphotypes of Podarcis wall
      lizards from the Iberian Peninsula and north Africa were estimated using partial
      12S rRNA and cytochrome b mitochondrial DNA sequences. All species except
      Podarcis hispanica form monophyletic units. P. hispanica is paraphyletic,
      although all identified morphotypes are monophyletic. These morphotypes represent
      highly divergent lineages showing 10-15% pairwise sequence divergence with the
      cytochrome b gene. The data suggest that P. hispanica is a species complex. We
      recommend using P. hispanica* until additional sampling delimits the number and
      ranges of species currently referred to P. hispanica. P. carbonelli, which has
      recently been raised to species status, is confirmed as a genetically distinct
      form. P. atrata is genetically distinct, but much more closely related to some
      populations of P. hispanica than previously thought.

PMID- 12182405
TI  - Chroococcidiopsis and heterocyst-differentiating cyanobacteria are each other's
      closest living relatives.
AB  - Many filamentous cyanobacteria reduce atmospheric nitrogen in specialized
      differentiated cells called heterocysts. Here we present evidence that shows that
      members of the unicellular non-heterocyst-differentiating genus Chroococcidiopsis
      and the filamentous heterocyst-differentiating cyanobacteria are each other's
      closest living relatives. Distance, maximum-parsimony, and maximum-likelihood
      analyses of complete small subunit ribosomal RNA gene sequences yielded highly
      congruent support for the monophyly of Chroococcidiopsis and the heterocyst
      differentiating cyanobacteria. Our results demonstrate that the order
      Pleurocapsales, which traditionally contains Chroococcidiopsis, is a polyphyletic
      assemblage with the ability to reproduce by multiple fission having arisen
      independently at least twice during the cyanobacterial radiation. Our data also
      reject Myxosarcina as a sister taxon to Chroococcidiopsis, indicating that the
      numerous presumed shared derived characters thought to unite the two genera
      evolved independently. The sequence divergence within the Chroococcidiopsis
      lineage is comparable to and probably exceeds that in the entire heterocyst
      differentiating lineage. Chroococcidiopsis forms unique survival cells under
      nitrogen-limiting conditions, and the sister group relationship with the
      heterocystous cyanobacteria shown here suggests that differentiation of these
      cells and heterocysts may be related processes.

PMID- 12182406
TI  - Mitochondrial 12S rDNA sequence relationships suggest that the enigmatic bovid
      "Linh Duong" Pseudonovibos spiralis is closely related to buffalo.
AB  - The phylogenetic position and taxonomic status of the recently described
      Southeast Asian endemic bovid Pseudonovibos spiralis were deduced from nearly
      complete 12S mitochondrial rDNA sequences of this species and Bubalus bubalis
      alongside 26 sequences of Bovidae from GenBank using Cervus elaphus (Cervidae) as
      outgroup. Maximum-likelihood analyses performed by PUZZLE and fastDNAml nested P.
      spiralis at the base of the subtribe buffalo Bovini, suggesting the close
      relationship of this enigmatic species with buffalo and enabling its distinction
      into the separate

PMID- 12182407
TI  - Treatment of chronic pain with spinal cord stimulation versus alternative
      therapies: cost-effectiveness analysis.
AB  - OBJECTIVE: There is limited available research measuring the cost-effectiveness
      of spinal cord stimulation (SCS), compared with best medical
      treatment/conventional pain therapy (CPT). The purpose of this study was to
      tabulate the actual costs (in Canadian dollars) for a consecutive series of
      patients treated with SCS in a constant health care delivery environment and to
      compare the costs with those for a control group treated in the same controlled
      environment. METHODS: We present a consecutive series of 104 patients with failed
      back syndrome. Within this group, 60 patients underwent SCS electrode
      implantation, whereas 44 patients were designated as control subjects. We
      monitored these patients for a 5-year period and tabulated the actual costs
      incurred in diagnostic imaging, professional fees paid to physicians,
      implantation (including the costs for hardware), nursing visits for maintenance
      of the stimulators, physiotherapy, chiropractic treatments, massage therapy, and
      hospitalization for treatment of breakthrough pain. From these data, the
      cumulative costs for each group were calculated for a 5-year period. An analysis
      of Oswestry questionnaire results was also performed, to evaluate the effects of
      treatment on the quality of life. RESULTS: The actual mean cumulative cost for
      SCS therapy for a 5-year period was $29,123/patient, compared with $38,029 for
      CPT. The cost of treatment for the SCS group was greater than that for the CPT
      group in the first 2.5 years. The costs of treating patients with SCS became less
      than those for CPT after that period and remained so during the rest of the
      follow-up period. In addition, 15% of SCS-treated patients were able to return to
      employment, because of superior pain control and lower drug intake. No patients
      in the control group were able to return to employment of any kind. CONCLUSION:
      SCS is cost-effective in the long term, despite the initial high costs of the
      implantable devices.

PMID- 12182408
TI  - Proposed use of prophylactic decompressive craniectomy in poor-grade aneurysmal
      subarachnoid hemorrhage patients presenting with associated large sylvian
      hematomas.
AB  - OBJECTIVE: As a group, patients who present in poor neurological grade after
      aneurysmal subarachnoid hemorrhage (SAH) often have poor outcomes. There may be
      subgroups of these patients, however, in which one pathological process
      predominates and for which the initiation of specific therapeutic interventions
      that target the predominant pathological process may result in improved outcome.
      We report the use of prophylactic decompressive craniectomy in patients
      presenting in poor neurological condition after SAH from middle cerebral artery
      aneurysms with associated large sylvian fissure hematomas. Craniectomy allowed
      significant parenchymal swelling in the posthemorrhagic period without increased
      intracranial pressure (ICP) or herniation syndrome. METHODS: Eight patients (mean
      age, 56.5 yr; age range, 42-66 yr) presented comatose with SAH (five Hunt and
      Hess Grade IV, three Hunt and Hess Grade V). Radiographic evaluations
      demonstrated middle cerebral artery aneurysm and associated large sylvian fissure
      hematoma (mean clot volume, 121 ml; range, 30-175 ml). Patients were brought
      emergently to the operating room and treated with a modification of the pterional
      craniotomy and aneurysm clipping that included a planned craniectomy and
      duraplasty. A large, reverse question mark scalp flap was created, followed by
      bone removal with the following margins: anterior, frontal to the midpupillary
      line; posterior at least 2 cm behind the external auditory meatus; superior up to
      2 cm lateral to the superior sagittal sinus; and inferior to the floor of the
      middle cranial fossa. Generous duraplasty was performed using either pericranium
      or suitable, commercially available dural substitutes. RESULTS: All of the eight
      patients tolerated the craniectomy without operative complications.
      Postoperatively, all patients experienced immediate decreases in ICP to levels at
      or below 20 mm Hg (presentation mean ICP, 31.6 mm Hg; postoperative mean ICP,
      13.1 mm Hg). ICP control was sustained in seven of eight patients, with the one
      exception being due to a massive hemispheric infarction secondary to refractory
      vasospasm. Follow-up (> or = 1 yr, except for one patient who died during the
      hospital stay) demonstrated that the craniectomy patients had a remarkably high
      number of good or excellent outcomes. The outcomes in the hemicraniectomy group
      were five good or excellent, one fair, and two poor or dead. CONCLUSION: The data
      gathered in this study demonstrate that decompressive craniectomy can be
      performed safely as part of initial management for a subcategory of patients with
      SAH who present with large sylvian fissure hematomas. In addition, the
      performance of decompressive craniectomy in the patients described in this
      article seemed to be associated with rapid and sustained control of ICP. Although
      the number of patients in this study is small, the data lend support to the
      hypothesis that decompressive craniectomy may be associated with good or
      excellent outcome in a carefully selected subset of patients with SAH.

PMID- 12182409
TI  - Trans-supraorbital approach to supratentorial aneurysms.
AB  - OBJECTIVE: The trans-supraorbital approach has the advantage of combining the
      keyhole principle with cranial base surgery. The anatomic fields that can be
      visualized with the use of this procedure have been demonstrated in cadavers, and
      the advantages and potential surgical applications of this procedure are
      described in this report. This article is the first to describe a group of
      intracranial supratentorial aneurysms. METHODS: We used the trans-supraorbital
      approach in 22 cases of supratentorial aneurysms. In this technique, an incision
      is made through the eyebrow, then a 3.5-cm craniotomy is performed with en bloc
      extension to the orbital arch, complemented by different drilling extensions of
      the orbital roof according to the surgical objective. We describe the anatomic
      details of the experimental work as well as the clinical results. RESULTS: The
      trans-supraorbital technique offers an unlimited wide exposure of neurovascular
      structures in this microsurgical corridor. The craniotomy extension allows
      greater exposure than the conventional keyhole supraorbital approach, which makes
      the technique safe for the patient and comfortable for the surgeon. All patient
      outcomes were successful; no serious complications from the surgical technique
      occurred. Our success was achieved through better microscopic illumination in the
      deep field and by gaining access to the complete supratentorial vascular
      territory with minimal cerebral retraction and an acceptable cosmetic result.
      CONCLUSION: The trans-supraorbital approach is effective for gaining access to
      and treating supratentorial aneurysms. Also, the microsurgical field is more
      convenient in microscope-assisted surgery because total reliance on the endoscope
      is not required, and minimal brain retraction is needed. This modification of the
      keyhole procedure also provides multiple surgical options in this microsurgical
      corridor, using the principles of minimal invasiveness in cranial base surgery.

PMID- 12182410
TI  - Image-guided endoscopic transnasal removal of recurrent pituitary adenomas.
AB  - OBJECTIVE: To assess the role that neuronavigation plays in assisting endoscopic
      transsphenoidal reoperations for recurrent pituitary adenomas. METHODS: During a
      45-month period, 19 endoscopic endonasal transsphenoidal reoperations were
      performed for recurrent pituitary adenomas. In 11 of 19 patients, the procedure
      was performed with the aid of an optically guided system. Clinical records were
      reviewed retrospectively, with attention to the following: comparison of baseline
      clinical data, the duration of surgery, and the postoperative course and
      complications of both image-guided and non-image-guided endoscopic reoperations.
      In addition, to test the reliability of the neuronavigation system, we made
      measurements of intraoperative accuracy in five additional transnasal endoscopic
      procedures in "virgin" noses and sphenoidal sinuses. RESULTS: In both groups
      studied, we found no difference with regard to either morbidity or mortality,
      which were null. The mean setup time was 13 minutes shorter in non-image-guided
      procedures (P = 0.021), and the operative time was 36 minutes shorter in image
      guided procedures (P = 0.038). No other statistically significant differences
      were found between the two groups. In all cases, we found that the system
      performed without malfunction. Continuous information regarding instrument
      location and trajectory was provided to the surgeon. Measurements of the
      intraoperative accuracy in the axial, coronal, and sagittal planes indicated a
      mean intraoperatively verified system error of 1.6 +/- 0.6 mm. CONCLUSION:
      Neuronavigation can be applied during endonasal transsphenoidal endoscopic
      surgery and requires a minimal amount of time. It makes reoperation easier,
      faster, and probably safer.

PMID- 12182411
TI  - Treatment of giant intracranial aneurysms with saphenous vein extracranial-to
      intracranial bypass grafting: indications, operative technique, and results in 29
      patients.
AB  - OBJECTIVE: The treatment of giant intracranial aneurysms is a challenge because
      of the limitations and difficulty of direct surgical clipping and endovascular
      coiling. We describe the indications, surgical technique, and complications of
      saphenous vein extracranial-to-intracranial bypass grafting followed by acute
      parent vessel occlusion in the management of these difficult lesions. METHODS:
      Between January 1990 and December 1999, 29 patients with giant intracranial
      aneurysms underwent 30 saphenous vein bypass grafts followed by immediate parent
      vessel occlusion. There were 11 men and 18 women with a mean follow-up period of
      62 months. Twenty-five patients harbored aneurysms involving the internal carotid
      artery, 2 had middle cerebral artery aneurysms, and 2 had aneurysms in the
      basilar artery. Serial cerebral or magnetic resonance angiograms were obtained to
      assess graft patency and aneurysm obliteration. RESULTS: All 30 aneurysms were
      excluded from the cerebral circulation, with 28 vein grafts remaining patent. Two
      patients had graft occlusions: one because of poor runoff and the other because
      of misplacement of a cranial pin during a bypass procedure on the contralateral
      side. Other surgical complications included one death from a large cerebral
      infarction, homonymous hemianopsia from thrombosis of an anterior choroidal
      artery after internal carotid artery occlusion, and temporary hemiparesis from a
      presumed perforator thrombosis adjacent to a basilar aneurysm. CONCLUSION: With
      appropriate attention to surgical technique, a saphenous vein extracranial-to
      intracranial bypass followed by acute parent vessel occlusion is a safe and
      effective method of treating giant intracranial aneurysms. A high rate of graft
      patency and adequate cerebral blood flow can be achieved. Thrombosis of
      perforating arteries caused by altered blood flow hemodynamics after parent
      vessel occlusion may be a continuing source of complications.

PMID- 12182412
TI  - Clinical and radiographic outcome in the management of posterior circulation
      aneurysms by use of direct surgical or endovascular techniques.
AB  - OBJECTIVE: Posterior circulation aneurysms can be difficult lesions to treat
      surgically, and they have potential for high morbidity and mortality,
      particularly in elderly patients or those in poor neurological condition. In an
      effort to improve outcomes, our combined neurosurgical and neuroendovascular unit
      has used both surgical clipping and endovascular coiling techniques to treat
      posterior circulation aneurysms. Patients considered at high risk for surgery
      were managed with endovascular treatment. METHODS: From 1990 to 1998, 197
      posterior circulation aneurysms in 189 patients were treated in our combined
      neurovascular unit. Of these aneurysms, 128 were ruptured, 63 were unruptured,
      and 6 had a distant history of rupture in patients who came to our center for
      delayed or repeat treatment. A total of 132 aneurysms were treated with surgical
      clipping (85 ruptured, 46 unruptured, and 1 with distant history of rupture) and
      65 aneurysms were treated with endovascular coiling (43 ruptured, 17 unruptured,
      and 5 with distant history of rupture). Dissecting aneurysms of the vertebral or
      posteroinferior cerebellar arteries or aneurysms treated with proximal
      (Hunterian) occlusion were excluded from this analysis. Surgical risk was
      assessed using a previously described system (Massachusetts General Hospital
      [MGH] grade), which incorporates age, Hunt and Hess grade, size of lesion, and
      Fisher grade. RESULTS: Overall clinical outcomes at 1 year of follow-up were
      77.2% excellent or good, 10.2% fair, 4.1% poor, and 8.6% dead. Surgical treatment
      resulted in 95.6% complete aneurysm occlusion and 4.4% with residual aneurysm
      after surgical treatment, whereas endovascular treatment resulted in 32.3%
      complete occlusion, 26.2% with residual aneurysm, and 41.5% with partial
      occlusion. In most cases, however, treatment with Guglielmi detachable coils
      (Boston Scientific/Target, Fremont, CA) was performed for palliation rather than
      complete radiographic occlusion. Outcome was closely associated with MGH grade
      with either treatment modality. Excellent/good outcomes were achieved in 96,
      92.3, 82.9, 46.2, and 0% of surgically treated patients with MGH Grades of 0, 1,
      2, 3, and 4, respectively. In comparison, excellent/good outcomes were achieved
      in 100, 84.2, 61.9, 0, and 50% of endovascularly treated patients with MGH Grades
      of 0, 1, 2, 3, and 4, respectively. CONCLUSION: A combined surgical and
      endovascular approach to posterior circulation aneurysms can achieve good
      outcomes in high-risk surgical patients treated by use of coiling techniques.

PMID- 12182413
TI  - Partial labyrinthectomy petrous apicectomy approach to the petroclival region: an
      anatomic and technical study.
AB  - OBJECTIVE: The petroclival region generally is thought to be an inaccessible area
      in the intracranial compartment. A number of ways of reaching this area during
      surgery have been described, including the presigmoid petrosal approach. The
      partial labyrinthectomy petrous apicectomy approach is a relatively new approach
      to this region and is a variant of the presigmoid petrosal approach. This study
      aims to demonstrate the technique and the microsurgical anatomy of the partial
      labyrinthectomy petrous apicectomy approach and to provide a quantitative study
      of its exposure to compare it with other common approaches to this region,
      particularly the presigmoid petrosal approach. METHODS: Bilateral stepwise
      dissections were performed on 15 formalin-fixed and dye-injected cadaveric heads
      (30 sides) under x3 to x40 magnification. A temporal craniotomy was performed
      after a complete mastoidectomy. A partial labyrinthectomy and petrous apicectomy
      were performed next. The amount of dura exposed was measured before and after the
      partial labyrinthectomy and the petrous apicectomy. By measuring the angles of
      exposure, the approach was examined to analyze how much increased access was
      gained. RESULTS: This approach provided wide exposure to the petroclival region,
      the cerebellopontine angle, Meckel's cave, the cavernous sinus, and the
      prepontine region. On average, there was an increase of 10.8 mm in horizontal
      exposure as compared with the retrolabyrinthine approach. The average angle of
      vision achieved with the clival pit as the target was 58.9 degrees. In most of
      the specimens, an area from the IIIrd to the IXth cranial nerves was easily
      visible without any significant brain retraction. A high jugular bulb did not
      reduce the exposure. CONCLUSION: The partial labyrinthectomy petrous apicectomy
      approach converts two narrow tunnels into a wide corridor. It increases the angle
      of exposure markedly, providing easy and excellent exposure of the otherwise
      difficult-to-access petroclival region, and it may also preserve hearing.

PMID- 12182414
TI  - Transsphenoidal microsurgery.
AB  - Transsphenoidal microsurgery is a well-established neurosurgical procedure that
      has become the standard of care in the management of the majority of pituitary
      tumors and a select group of other sellar lesions. The safety of the procedure
      depends on the surgeon's adherence to certain anatomic concepts. Foremost among
      these concepts is the necessity of preserving the integrity of the arachnoid
      membrane covering the tumor dome and avoiding vascular injuries in the cavernous
      sinus. The objective of this article is to demonstrate the sequential steps of a
      transsphenoidal microsurgical procedure for the removal of a pituitary tumor in
      light of the anatomic concepts discussed, with the goal of preventing
      complications and achieving the best possible outcome.

PMID- 12182415
TI  - Ventriculostomy-related infections: a critical review of the literature.
AB  - OBJECTIVE: To provide a critical evaluation of the published literature
      describing risk factors for ventriculostomy-related infections (VRIs) and the
      efficacy of prophylactic catheter exchange. METHODS: A MEDLINE literature search
      was performed, and data were extracted from studies published from 1941 through
      2001. RESULTS: Published criteria for diagnosing VRIs are highly variable.
      Intraventricular hemorrhage, subarachnoid hemorrhage, cranial fracture with
      cerebrospinal fluid leak, craniotomy, systemic infections, and catheter
      irrigation all predispose patients to the development of VRIs. Extended duration
      of catheterization is correlated with an increasing risk of cerebrospinal fluid
      infections during the first 10 days of catheterization. Prophylactic catheter
      exchange does not modify the risk of developing later VRIs in retrospective
      studies. CONCLUSION: Categorizing suspected cerebrospinal fluid infections as
      contaminants, colonization, suspected or confirmed VRIs, or ventriculitis more
      accurately describes the patient's clinical condition and may indicate different
      management strategies. A prospective, randomized clinical trial is required to
      further evaluate the efficacy of prophylactic catheter exchange in limiting the
      incidence of VRIs during prolonged catheterization. Although prophylactic
      catheter exchange remains a practice option, the available data suggest that this
      procedure is not currently justified.

PMID- 12182416
TI  - Tenascin in meningioma: expression is correlated with anaplasia, vascular
      endothelial growth factor expression, and peritumoral edema but not with tumor
      border shape.
AB  - OBJECTIVE: Tenascin is an extracellular matrix glycoprotein that is expressed
      during embryogenesis, inflammation, angiogenesis, and carcinogenesis. The aim of
      this study was to investigate how tenascin expression relates to histological
      grade, angiogenesis, and radiological findings in meningiomas. METHODS: Twenty
      typical, 20 atypical, and 5 malignant meningiomas were studied retrospectively.
      Tenascin expression and vascular endothelial growth factor (VEGF) expression in
      the tumor tissue were investigated by immunohistochemistry. Tenascin messenger
      ribonucleic acid expression was also studied by comparative reverse transcriptase
      polymerase chain reaction. Magnetic resonance images from each case were assessed
      for peritumoral edema and tumor border shape. RESULTS: The atypical and malignant
      meningiomas showed higher levels of tenascin expression than the typical
      meningiomas. The more sensitive messenger ribonucleic acid-based methods
      confirmed this finding. Tenascin expression was correlated with peritumoral edema
      and VEGF expression but not with tumor border shape. In the 13 tumors with marked
      tenascin expression, peritumoral edema was Grade 0 in one, Grade 1 in three, and
      Grade 2 in nine specimens. In the same 13 tumors, VEGF expression was Grade 1 in
      five and Grade 2 in eight specimens, and the findings for tumor border shape were
      Grade 0 in seven, Grade 1 in four, and Grade 2 in two specimens. CONCLUSION: In
      meningiomas, tenascin expression is correlated with anaplasia, tumor-associated
      edema, and VEGF expression but not with tumor border shape. This protein may play
      a role in the neoplastic and/or angiogenic processes in atypical and malignant
      meningiomas and may thus be a potential target for meningioma therapy.

PMID- 12182417
TI  - Interleukin-1beta messenger ribonucleic acid and protein levels after fluid
      percussion brain injury in rats: importance of injury severity and brain
      temperature.
AB  - OBJECTIVE: Posttraumatic temperature manipulations have been reported to
      significantly influence the inflammatory response to traumatic brain injury
      (TBI). The purpose of this study was to determine the temporal and regional
      profiles of messenger ribonucleic acid (mRNA) expression and protein levels for
      the proinflammatory cytokine interleukin-1beta (IL-1beta), after moderate or
      severe TBI. The effects of posttraumatic hypothermia (33 degrees C) or
      hyperthermia (39.5 degrees C) on these consequences of TBI were then determined.
      METHODS: Male Sprague-Dawley rats underwent fluid-percussion brain injury. In the
      first phase of the study, rats were killed 15 minutes or 1, 3, or 24 hours after
      moderate TBI (1.8-2.2 atmospheres), for reverse transcription-polymerase chain
      reaction analysis. Other groups of rats were killed 1, 3, 24, or 72 hours after
      moderate or severe TBI (2.4-2.7 atmospheres), for protein analysis. In the second
      phase, rats underwent moderate fluid-percussion brain injury, followed
      immediately by 3 hours of posttraumatic normothermia (37 degrees C), hyperthermia
      (39.5 degrees C), or hypothermia (33 degrees C), and were then killed, for
      analyses of protein levels and mRNA expression. Brain samples, including cerebral
      cortex, hippocampus, thalamus, and cerebellum, were dissected and stored at -80
      degrees C until analyzed. RESULTS: The findings indicated that mRNA levels were
      increased (P < 0.05) as early as 1 hour after TBI and remained elevated up to 3
      hours after moderate TBI. Although both moderate and severe TBI induced increased
      levels of IL-1beta (P < 0.05), increased protein levels were also noted in remote
      brain structures after severe TBI. Posttraumatic hypothermia attenuated IL-1beta
      protein levels, compared with normothermia (P < 0.05), although the levels
      remained elevated in comparison with sham values. In contrast, hyperthermia had
      no significant effect on IL-1beta levels, compared with normothermic values.
      Posttraumatic temperature manipulations had no significant effect on IL-1beta
      mRNA levels. CONCLUSION: Injury severity determines the degree of IL-1beta
      protein level elevation after TBI. The effects of posttraumatic hypothermia on IL
      1beta protein levels (an important mediator of neurodegeneration after TBI) may
      partly explain the established effects of posttraumatic temperature manipulations
      on inflammatory processes after TBI.

PMID- 12182418
TI  - Necrosis and glioblastoma: a friend or a foe? A review and a hypothesis.
AB  - OBJECTIVE: Two main forms of cell death are encountered in biology: apoptosis
      (i.e., programmed cell death) and necrosis (i.e., accidental cell death). Because
      necrosis and apoptosis can lead to cell removal, one might intuit that they are
      both desirable in cancer treatment. However, in the setting of glioblastoma
      multiforme, a malignant brain tumor for which the presence of necrosis is an
      important diagnostic feature, clinical studies indicate that as the degree of
      necrosis advances, the patient's prognosis worsens. Despite the apparent
      importance of this form of cell death, the mechanism of development of necrosis
      in glioblastomas remains unelucidated. The purpose of this article is to try to
      resolve this dilemma by hypothesizing the mechanism of necrosis formation in
      these tumors. METHODS: On the basis of an extensive review of the literature, we
      present a hypothesis for the mechanism of necrosis formation in glioblastoma
      multiforme. RESULTS: One of the many possible pathways leading to necrosis
      formation may involve increased tumor cell secretion of tumor necrosis factor.
      Procoagulation and antiapoptotic mechanisms resulting from certain pathways could
      prevent the completion of tumor necrosis factor-induced apoptosis and could
      promote necrosis as the final mode of cell death. Such a hypothesis would explain
      the inverse correlation that exists between tumor necrosis and the survival of
      patients with glioblastomas, because the hypoxia that results from procoagulation
      selects for tumor cells that are more aggressive and more resistant to apoptosis
      inducing therapies. CONCLUSION: A complete understanding of the series of events
      surrounding necrosis development in glioblastomas that is evidence-based is
      likely to provide targets for future therapies. On the basis of the potential
      mechanisms of development of necrosis described in this article, we postulate
      that effective therapies may have to be directed against the pathways that result
      in the formation of necrosis.

PMID- 12182419
TI  - Heat shock protein expression in cerebral vessels after subarachnoid hemorrhage.
AB  - OBJECTIVE: The mechanisms of cerebral vasospasm after subarachnoid hemorrhage
      (SAH) remain controversial. Recent data have implicated two small heat shock
      proteins (HSPs), namely HSP20 and HSP27, in the regulation of vascular tone.
      Increases in the phosphorylation of HSP20 are associated with vasorelaxation, and
      increases in the phosphorylation of HSP27 are associated with impaired
      vasorelaxation. Therefore, we hypothesized that alterations in the expression
      and/or phosphorylation of these two small HSPs might play a role in cerebral
      vasospasm after SAH. METHODS: A rat model of endovascular perforation was used to
      induce SAH. Middle cerebral arteries were harvested from control animals, sham
      treated animals, and animals with SAH, 48 hours after SAH induction. Dose
      response curves for endothelium-independent (sodium nitroprusside, 10(-8) to 10(
      4) mol/L) and endothelium-dependent (bradykinin, 10(-10) to 10(-5) mol/L)
      relaxing agents were recorded ex vivo. Physiological responses were correlated
      with the expression and phosphorylation of HSP20 and HSP27 by using one- and two
      dimensional immunoblots. RESULTS: There was impaired endothelium-independent and
      endothelium-dependent relaxation in cerebral vessels after SAH. These changes
      were associated with decreased expression of both total and phosphorylated HSP20
      and increases in the amount of phosphorylated HSP27. CONCLUSION: In this model,
      impaired relaxation of cerebral vessels after SAH was associated with increases
      in the amount of phosphorylated HSP27 and decreases in the expression and
      phosphorylation of HSP20. These data are consistent with alterations in the
      expression and phosphorylation of these small HSPs in other models of vasospasm.

PMID- 12182420
TI  - Effect of trapidil in ischemia/reperfusion injury of peripheral nerves.
AB  - OBJECTIVE: Ischemia plays an important role in the development of pathological
      changes in nerve tissue, and restoration of blood flow results in injury
      (ischemia/reperfusion [I/R] injury) mediated by toxic oxygen free radicals.
      Trapidil is currently used as a coronary artery vasodilating agent and is also
      used for the prevention of ischemic symptoms of cerebral vasospasm. The purpose
      of this study was to determine the effects of trapidil on I/R injury and the
      ischemic tolerance of rat peripheral nerves. METHODS: Preischemia or
      prereperfusion administration of trapidil (8 mg/kg) was evaluated in the rat
      sciatic nerve I/R injury model. Nerve tissue samples from the I/R injury site
      were assayed for malondialdehyde (MDA), nitrites, and nitrates, as markers of I/R
      injury, and pathological changes were evaluated by electron microscopy. RESULTS:
      I/R resulted in an increase in MDA levels, which remained elevated for 2 weeks in
      control nerves. Rats that received trapidil before ischemia exhibited decreased
      MDA levels, and rats that received trapidil after the standard 3 hours of
      ischemia demonstrated increased tolerance to reperfusion, as reflected in
      significantly decreased MDA levels. Nitrite and nitrate levels in trapidil
      treated rats were significantly higher than those in control animals.
      Histological evaluations of the sciatic nerve segments demonstrated that
      preischemia and postischemia trapidil treatments had a sparing effect against the
      myelin damage and axonal edema that are consistently noted in untreated ischemic
      reperfused nerves. CONCLUSION: The results confirm that pretreatment with
      trapidil before the ischemic insult or before reperfusion provides marked
      protection against I/R injury in peripheral nerves.

PMID- 12182421
TI  - Isolated, giant cerebellopontine angle craniopharyngioma in a patient with
      Gardner syndrome: case report.
AB  - OBJECTIVE AND IMPORTANCE: We report the case of a 29-year-old man with Gardner
      syndrome and an isolated, giant cerebellopontine angle craniopharyngioma. Our
      description of this patient is only the second case report of a craniopharyngioma
      arising primarily in the cerebellopontine angle. CLINICAL PRESENTATION: The
      patient presented with a 1-year history of progressive neurological impairment
      and headache. On the basis of the patient's history of multiple dermal fibromas,
      a cranial osteoma, familial adenomatous polyposis (FAP), a total abdominal
      colectomy, and an adenoma of the ampulla of Vater, we diagnosed the patients
      condition as Gardner syndrome. INTERVENTION: Magnetic resonance imaging showed a
      large cerebellopontine angle tumor, which was removed through a suboccipital
      retromastoid craniotomy. The pathological features were those of an
      adamantinomatous craniopharyngioma. The patient has done well postoperatively and
      has no new neurological deficits. A careful retrospective review of the
      preoperative imaging shows that this tumor was located exclusively in the
      posterior fossa and was not an extension of a sellar, suprasellar, or clival
      craniopharyngioma. CONCLUSION: We present the second reported case of FAP and
      craniopharyngioma. There is no known genetic link between FAP and
      craniopharyngioma. Now that the patient has manifested a primary tumor of the
      central nervous system with FAP, it is unclear whether he should be classified as
      having Turcot syndrome. For this patient, we recommended vigilant follow-up
      imaging and forgoing external beam radiotherapy unless there is a documented
      recurrence of his craniopharyngioma.

PMID- 12182422
TI  - Familial medulloblastoma: case report of one family and review of the literature.
AB  - OBJECTIVE AND IMPORTANCE: Medulloblastoma is the most common malignant brain
      tumor and the most common malignant solid tumor in children. Most
      medulloblastomas are sporadic, but rare familial forms have been described. To
      the best of our knowledge, only 10 case reports of familial medulloblastoma have
      been published. A variety of candidate genes have been suggested to be involved
      in familial medulloblastomas. However, the exact pathogenesis and genetics
      involved in familial medulloblastoma remain unknown. CLINICAL PRESENTATION: We
      describe the presentation of medulloblastoma in two siblings (one of each sex)
      and their great-uncle. The three cases differ with regard to age at onset and
      pathological subtype of medulloblastoma. INTERVENTION OR TECHNIQUE:
      Immunostaining of tissue blocks for gene products involved in medulloblastoma
      differed in the two siblings for beta-catenin and was similar with staining for
      gli. CONCLUSION: This article is only the second report in the literature to
      address the genetics of familial medulloblastoma in the absence of characterized
      conditions such as Li-Fraumeni's cancer syndrome and basal cell nevus, Rubinstein
      Taybi's, and Turcot's syndromes. The discrepancy in beta-catenin staining in the
      two siblings suggests that the two tumors differentiated through divergent
      pathways. We briefly summarize all published cases of familial medulloblastoma
      and review the literature on the genes involved in medulloblastoma formation.

PMID- 12182423
TI  - Angioplasty for intracranial symptomatic vertebrobasilar ischemia.
AB  - OBJECTIVE: Although anterior circulation disease has both medical and surgical
      treatment options, management of vertebrobasilar disease has predominantly had
      only medical options. Some patients remain symptomatic despite medical treatment,
      and angioplasty has been demonstrated to relieve critical stenoses. However, the
      elative safety and effectiveness of medical and surgical treatments is not
      clearly known. This report reviews the clinical characteristics, indications, and
      procedural risks of intracranial angioplasty in a series of patients with
      symptomatic posterior circulation ischemia. METHODS: All patients undergoing
      angioplasty for critical intracranial vertebral or basilar artery stenosis at the
      University of California at San Francisco Medical Center between June 1986 and
      July 1999 were included in a retrospective record review. Clinical features and
      procedural complications were recorded. RESULTS: Angioplasty was performed on 25
      vessel lesions in 25 patients in whom medical therapy had failed. The patients
      ranged in age from 50 to 87 years. Of the 25 stenoses, 10 were intracranial
      vertebral, 9 vertebrobasilar junction, and 6 basilar in location. Angioplasty was
      effective in reducing the degree of stenosis by more than 40% in all 25 vessels.
      The overall risk of stroke or death was 28%, and the risk of disabling stroke or
      death was 16%. CONCLUSION: Intracranial posterior circulation angioplasty is
      effective in the reduction of stenosis and can be performed with relative safety.
      Angioplasty can be considered as a treatment option in patients with recurrent
      ischemic symptoms despite medical therapy.

PMID- 12182424
TI  - Endovascularly treated cerebral aneurysm using Guglielmi detachable coils acting
      as a nidus for brain abscess formation secondary to Salmonella bacteremia: case
      report.
AB  - OBJECTIVE AND IMPORTANCE: Intracranial infections related to the various foreign
      materials used to secure intracranial aneurysms are extremely rare. The lack of
      neoendothelium formation across the necks of aneurysms, which is particularly
      prone to occur when the sac is incompletely packed by Guglielmi detachable coils
      (GDC), results in the absence of isolation of the coils from the circulation.
      Colonization of GDCs, which act as a foreign-body nidus after hematogenous spread
      from infections with bacteremia, may result in localized intracranial infection.
      CLINICAL PRESENTATION: A 55-year-old woman developed meningitis and a brain
      abscess surrounding a giant aneurysm that was treated endovascularly with GDC 3
      1/2 years earlier. Four weeks before she sought care, she experienced an
      infective illness with proven Salmonella bacteremia. Salmonella group D was
      isolated from cerebrospinal fluid. INTERVENTION: The patient was treated
      successfully with long-term cephalosporin therapy. Follow-up imaging studies
      revealed regression of the abscess. CONCLUSION: This case suggests that the GDC
      acted as a colonized foreign body, resulting in the surrounding abscess formation
      after infection with Salmonella bacteremia. Alternatively, the reaction of the
      surrounding tissue to the GDC was the predisposing factor and acted as the nidus
      for the abscess formation.

PMID- 12182425
TI  - Cervical spinal cord compression attributable to a calcified intervertebral disc
      in a patient with X-linked hypophosphatemic rickets: case report and review of
      the literature.
AB  - OBJECTIVE AND IMPORTANCE: X-linked hypophosphatemic rickets is a common inherited
      phosphate-wasting disorder, but it is a rare cause of spinal cord compression. We
      present the first reported case of a calcified intervertebral disc causing spinal
      canal stenosis in X-linked hypophosphatemic rickets. CLINICAL PRESENTATION: A 44
      year-old woman presented with paresthesia of her left arm and a loss of grip in
      both hands. Magnetic resonance imaging revealed a calcified intervertebral disc,
      as well as a posterior osteophytic bar causing marked cervical cord compression
      at C6/C7. INTERVENTION: An anterior cervical discectomy at C6/C7 and fusion with
      autologous bone graft were performed. The patient then exhibited significant
      improvement. CONCLUSION: A review of the 16 published cases demonstrates that
      thickening of the vertebral laminae, facet joint hypertrophy, and ossification of
      the intervertebral discs, posterior longitudinal ligament, and/or ligamentum
      flavum contribute to spinal canal stenosis in X-linked hypophosphatemic rickets.
      Those changes are caused by the disease itself and are unlikely to be related to
      long-term vitamin D treatment. Eleven of 16 patients were reported to have
      experienced favorable outcomes after surgery.

PMID- 12182426
TI  - Heterotopic ossification of peripheral nerve ("neuritis ossificans"): report of
      two cases.
AB  - OBJECTIVE AND IMPORTANCE: Heterotopic ossification ("neuritis ossificans") is
      among the least frequently encountered reactive lesions in peripheral nerves.
      Only two cases have been described previously, one in the median nerve of a 34
      year-old man, and the other in the ulnar nerve of an adult woman. The
      architecture of this lesion is distinctly zonal. Consisting of a central
      fibroblastic core, an intervening zone of osteoid production, and a peripheral
      layer of ossification, the pattern is remarkably similar to that of myositis
      ossificans. This similarity and the occurrence of the process in superficial
      nerves have led to speculation that trauma plays a role in its pathogenesis; this
      hypothesis remains unproved. We describe two additional cases of neuritis
      ossificans. CLINICAL PRESENTATION: One patient, a 41-year-old man, experienced
      pain and numbness in the left leg for several months but had no history of local
      trauma. A mass was detected in the saphenous nerve. The second patient, a 16-year
      old boy, noted subacute onset of pain in the popliteal fossa and decreased
      sensation in the distribution of the lateral sural cutaneous nerve. A mass was
      found within the tibial nerve at the knee level. INTERVENTION: In each patient,
      resection of the mass required sacrifice of a segment of the nerve. CONCLUSION:
      In each patient, the mass was composed of fibrovascular tissue with osteoid and
      bone deposition arranged in a zonal pattern. The ossifying process was
      intraneural but encased rather than directly involving nerve fascicles. These
      exceptionally intact examples of neuritis ossificans underscore its resemblance
      to myositis ossificans. Nerve-sparing resection of such masses is not always
      possible.

PMID- 12182427
TI  - Covered stent-graft repair of the brachiocephalic arteries: technical note.
AB  - OBJECTIVE: The use of a covered stent-graft to repair disruptions of the cervical
      carotid and vertebral arteries is described. This device maintains vessel patency
      while effectively excluding pseudoaneurysms, arteriovenous fistulae, and other
      breaches in the integrity of the arterial wall. METHODS: Patient 1 bled from a
      large rent in the proximal common carotid artery as a result of tumor invasion.
      Patient 2 developed a vertebral arteriovenous fistula after a stab injury to the
      neck. Patient 3 developed cerebral infarction and an enlarging pseudoaneurysm of
      the internal carotid artery, also after a stab wound to the neck. RESULTS: All
      three patients were treated with the Wallgraft endoprosthesis (Boston Scientific,
      Watertown, MA). In each case, the vessel wall defect was repaired while antegrade
      flow through the artery was preserved or restored. No neurological complications
      occurred as a result of stent-graft deployment. CONCLUSION: Covered stent-grafts
      offer an alternative to endovascular occlusion of the parent vessel, thereby
      expanding the therapeutic options for patients with extracranial cerebrovascular
      disease. These three cases highlight the usefulness and versatility of these
      devices for endoluminal reconstruction of the brachiocephalic vasculature.

PMID- 12182429
TI  - Trapping and revascularization for a dissecting aneurysm of the proximal
      posteroinferior cerebellar artery: technical case report and review of the
      literature.
AB  - OBJECTIVE AND IMPORTANCE: Subarachnoid hemorrhage caused by an isolated
      dissection of the proximal portion of the posteroinferior cerebellar artery
      (PICA) is a rare problem. The optimal treatment to use for patients presenting
      with this clinical scenario varies and therefore is controversial in the
      literature. We report a patient in whom this problem was treated effectively with
      trapping of the diseased segment and revascularization of the PICA. We report
      this case to review this rare topic and to present our perspective on the
      indications for and the effectiveness of trapping and revascularization for
      proximal PICA dissections that cause hemorrhage. CLINICAL PRESENTATION: A 55-year
      old man was transferred to our institution and admitted for Hunt and Hess Grade
      IV subarachnoid hemorrhage, which improved to Hunt and Hess Grade III after
      ventricular drainage. Imaging revealed the source of the hemorrhage to be a
      pseudoaneurysm related to the dissection of the proximal portion of the PICA.
      INTERVENTION: Three days after the initial bleeding episode, we operated on the
      patient. After the occipital artery was prepared for bypass, the diseased segment
      was trapped. The occipital artery-to-PICA anastomosis was then immediately
      performed distal to the trapped segment. CONCLUSION: On the basis of our
      experience, the literature regarding this topic, and the anatomy of the
      perforators of the PICA, we think that the best treatment for a pseudoaneurysm
      located within the first three segments of the PICA is trapping of the diseased
      segment followed by revascularization distal to the trapped segment. This
      approach should prevent rehemorrhage and should avoid iatrogenic ischemic
      complications of the brainstem.

PMID- 12182428
TI  - Clinical and hemodynamic responses to balloon test occlusion of the straight
      sinus: technical case report.
AB  - OBJECTIVE AND IMPORTANCE: Surgical sacrifice of the straight sinus may be
      performed during intracranial tumor resection. Sacrifice of the straight sinus is
      associated with an unpredictable risk of venous infarction. We describe a patient
      with a falcine meningioma who underwent endovascular balloon test occlusion of
      the straight sinus before surgical resection. CLINICAL PRESENTATION: A 48-year
      old woman presented with symptoms resulting from a 4-cm-diameter meningioma in
      the left occipital region. Along its inferior margin, the tumor abutted the
      straight sinus. Cerebral angiography demonstrated occlusion of the posterior one
      third of the superior sagittal sinus but patency of the straight sinus.
      TECHNIQUE: A 4-mm angioplasty balloon was directed into the straight sinus via
      the right jugular vein. In addition to clinical assessments, the pressure within
      the proximal straight sinus, upstream from the balloon, was measured before and
      during inflation. Severe headaches followed balloon inflation, and the pressure
      in the proximal straight sinus increased 18 mm Hg. With balloon deflation, the
      clinical and hemodynamic findings immediately returned to normal. On the basis of
      these findings, the straight sinus was preserved during surgery. CONCLUSION: This
      technique is straightforward and allows some assessment of the physiological
      responses and individual tolerance to sinus occlusion before surgery.

PMID- 12182430
TI  - Three-dimensional bone-free rendering of the cerebral circulation by use of
      computed tomographic angiography and fuzzy connectedness.
AB  - INTRODUCTION: Three-dimensional computed tomographic angiography (3-D-CTA) can be
      used to evaluate cerebrovascular disease. A potential limitation of this
      technology is obscuration of vascular anatomy by bone. In view of this, we
      developed a method for bone-free rendering using iterative relative fuzzy
      connectedness (IRFC) of 3-D-CTA to examine the cerebral vasculature without the
      intervening cranial base. METHODS: 3-D-CTA was obtained in 10 patients with
      cerebrovascular disease by use of an algorithm based on IRFC. Bone structures
      were removed and vascular anatomy was isolated with an almost completely
      automated process. Bone-removed images were rendered via maximum intensity
      projections, compared with digital subtraction angiography, and evaluated for
      vascular abnormalities. RESULTS: Compared with digital subtraction angiography,
      IRFC 3-D-CTA successfully defined the intracranial vascular anatomy in all 10
      patients. An aneurysm was identified in 6 patients, bilateral carotid-cavernous
      fistulae in 1 patient, and no structural abnormalities in the remaining 3
      patients. CONCLUSION: In 3-D-CTA, our preliminary findings suggest that bone
      obscuration, one of the current limitations of CTA, can be overcome through
      appropriate computer algorithms. We are now working on improving the
      computational efficiency of these algorithms to allow routine use of IRFC 3-D-CTA
      in an interventional or surgical suite.

PMID- 12182431
TI  - Novel multipurpose bipolar instrument for endoscopic neurosurgery.
AB  - OBJECTIVE: Hemorrhage control in endoscopic neurosurgery is critical because of
      the lack of suitable instruments for coagulation. One reason for this problem is
      that miniaturization of the instruments is still a technical problem. In this
      article, we present a solution: the use of bipolar microforceps with a small
      diameter of 1.5 mm. METHODS: With the use of modern synthetic and metallic
      materials, the construction of the bipolar microforceps was designed without the
      use of mechanical joints. All movable elements are integrated within the
      instrument shaft. This design provides optimal visibility of the operating field
      because the sheath has a diameter of only 1.5 mm along its entire length.
      Therefore, this instrument is compatible with most working channels of
      neuroendoscopes. RESULTS: The new, joint-free design of the forceps and the
      electric insulation of the branches were the technical innovations that led to
      the development of this novel, multipurpose instrument. CONCLUSION: This new
      instrument may enhance endoscopic resection and shrinkage of cystic lesions and
      may offer new possibilities in endoscopic tumor resection and the treatment of
      hemorrhage.

PMID- 12182432
TI  - MicroGuide microelectrode recording system.

PMID- 12182433
TI  - Multimodal quantitation of the effects of endovascular therapy for vasospasm on
      cerebral blood flow, transcranial doppler ultrasonographic velocities, and
      cerebral artery diameters.
AB  - OBJECTIVE: The goal of this study was to quantify the effects of endovascular
      therapy on vasospastic cerebral vessels. METHODS: We reviewed the medical records
      for 387 patients with ruptured intracranial aneurysms who were treated at a
      single institution (University of California, Los Angeles) between May 1, 1993,
      and March 31, 2001. Patients who developed cerebral vasospasm and underwent
      cerebral arteriographic, transcranial Doppler ultrasonographic, and cerebral
      blood flow (CBF) studies before and after endovascular therapy for cerebral
      arterial spasm (vasospasm) were included in this study. RESULTS: Forty-five
      patients fulfilled the aforementioned criteria and were treated with either
      papaverine infusion, papaverine infusion with angioplasty, or angioplasty alone.
      After balloon angioplasty (12 patients), CBF increased from 27.8 +/- 2.8 ml/100
      g/min to 28.4 +/- 3.0 ml/100 g/min (P = 0.87); the middle cerebral artery blood
      flow velocity was 1 57.6 +/- 9.4 cm/s and decreased to 76.3 +/- 9.3 cm/s (P <
      0.05), with a mean increase in cerebral artery diameters of 24.4%. Papaverine
      infusion (20 patients) transiently increased the CBF from 27.5 +/- 2.1 ml/100
      g/min to 38.7 +/- 2.8 ml/100 g/min (P < 0.05) and decreased the middle cerebral
      artery blood flow velocity from 109.9 +/- 9.1 cm/s to 82.8 +/- 8.6 cm/s (P <
      0.05). There was a mean increase in vessel diameters of 30.1% after papaverine
      infusion. Combined treatment (13 patients) significantly increased the CBF from
      33.3 +/- 3.2 ml/100 g/min to 41.7 +/- 2.8 ml/100 g/min (P< 0.05) and decreased
      the transcranial Doppler velocities from 148.9 +/- 12.7 cm/s to 111.4 +/- 10.6
      cm/s (P < 0.05), with a mean increase in vessel diameters of 42.2%. CONCLUSION:
      Balloon angioplasty increased proximal vessel diameters, whereas papaverine
      treatment effectively dilated distal cerebral vessels. In our small series, we
      observed no correlation between early clinical improvement or clinical outcomes
      and any of our quantitative or physiological data (CBF, transcranial Doppler
      velocities, or vessel diameters).

PMID- 12182434
TI  - Malignant pineal parenchymal tumors in adult patients: patterns of care and
      prognostic factors.
AB  - OBJECTIVE: The aim of our study was to analyze patterns of care and to identify
      prognostic factors in patients at least 18 years of age who received radiotherapy
      for malignant pineal parenchymal tumors. METHODS: In a multicenter, retrospective
      study, we analyzed data for 37 previously published cases and 64 patients treated
      at the participating institutions. RESULTS: A total of 56 patients received
      postoperative radiotherapy, and 45 patients received primary radiotherapy.
      Chemotherapy was administered to 34 patients. The median follow-up period was 38
      months, and median overall survival was 100 months. The variables that
      significantly influenced overall survival were the extent of disease (localized
      versus disseminated; P = 0.0002), differentiation (pineal parenchymal tumor of
      intermediate differentiation versus pineoblastoma; P = 0.001), and residual
      disease (> or = 50% versus < 50% reduction in size; P < 0.0001). In a
      multivariate analysis, the parameters turned out to be independent risk factors.
      The median survival in patients with local or spinal failure was 15 months. Local
      control was better in older patients (> or = 32 yr versus < 32 yr; P = 0.02).
      Spinal control was more successful in patients with pineal parenchymal tumors of
      intermediate differentiation than it was in patients with pineoblastomas (P =
      0.03). Nine of 45 treatment failures occurred later than 5 years after treatment.
      CONCLUSION: Stage, histological characteristics, and response are independent
      risk factors in adults with malignant pineal parenchymal tumors. Late relapses
      are common.

PMID- 12182435
TI  - Transsphenoidal surgery for Cushing's disease: endocrinological follow-up
      monitoring of 82 patients.
AB  - OBJECTIVE: Transsphenoidal surgery is the preferred treatment modality for
      adrenocorticotropic hormone-secreting pituitary adenomas. In the past 2 decades,
      several institutions in the United States and Europe have reported remission
      rates of 70 to 85% after transsphenoidal surgery for treatment of Cushing's
      disease. We analyzed our postoperative results for a large cohort of patients
      with Cushing's disease. METHODS: Eighty-two patients with adrenocorticotropic
      hormone-secreting adenomas (79 microadenomas and 3 macroadenomas) underwent
      transsphenoidal surgery between 1990 and 2000. Seventy-seven patients were
      surgically treated for the first time, and 13 patients underwent reoperations (5
      had undergone the first operation elsewhere) because of previous surgical failure
      (10 patients) or recurrence (3 patients). The mean postoperative follow-up period
      was 4.2 +/- 2.8 years. Biochemical remission was defined as postoperative
      normalization of elevated 24-hour urinary free cortisol secretion and suppression
      of morning cortisol levels with 1 mg of dexamethasone. RESULTS: Remission was
      achieved for 78% of all patients after one operation and for 62% of patients who
      underwent a second operation. The recurrence rate was 5%. Ten patients did not
      exhibit a visible tumor on magnetic resonance imaging scans, and the other
      patients were divided according to adenoma size (2-5 or 6-10 mm). Remission rates
      were similar for the three groups of patients (78-80%). Pituitary tumor stained
      for adrenocorticotropic hormone was detected in 78% of resected pituitary tissue
      specimens obtained from patients who achieved remission, compared with 53% from
      patients who experienced surgical failure (P = 0.06). CONCLUSION: Our series
      demonstrates the efficacy of transsphenoidal surgery for Cushing's disease
      resulting from pituitary microadenomas. Microadenoma size had no effect on the
      remission rate. Reoperations are indicated after initial surgical failures.

PMID- 12182436
TI  - Long-term control of hydrocephalus via endoscopic third ventriculostomy in
      children with tectal plate gliomas.
AB  - OBJECTIVE: We report the control of hydrocephalus in children with presumed
      tectal plate gliomas by the use of endoscopic third ventriculostomy (ETV).
      METHODS: The hospital records, office charts, and imaging studies from children
      who underwent ETV at the Children's Hospital of Alabama were reviewed. Thirteen
      children with the diagnosis of tectal plate glioma and hydrocephalus were
      identified. ETV was the primary therapy instituted for all but one of these
      children. Successful treatment outcome was defined as shunt freedom, improvement
      in symptoms, and reduced ventricular size. RESULTS: Thirteen children underwent a
      total of 15 ETVs, and all children were shunt-free at their most recent follow-up
      examinations. One child underwent successful secondary ETV, one child underwent
      shunt removal concomitant with the initial ETV, and one child underwent shunt
      removal concomitant with secondary ETV. Symptoms and signs resolved in all
      patients. All postoperative cranial imaging studies revealed normal or reduced
      ventricular size as compared with preoperative cranial imaging scans. The median
      follow-up period was 31 months. CONCLUSION: In our surgical experience, ETV has
      been uniformly successful in the management of hydrocephalus caused by tectal
      plate gliomas in children. ETV should be considered the treatment of choice for
      hydrocephalus in pediatric patients with tectal plate gliomas.

PMID- 12182437
TI  - A cost-effectiveness analysis of endoscopic third ventriculostomy.
AB  - OBJECTIVE: Endoscopic third ventriculostomy (ETV) is currently the principal
      alternative to cerebrospinal fluid shunt placement in the management of pediatric
      hydrocephalus. Cost-effectiveness analysis can help determine the optimal
      strategy for integrating these different approaches. METHODS: All patients (n =
      28) who underwent ETV at British Columbia's Children's Hospital between 1989 and
      1998 were matched for age, pathogenesis, and number of previous shunt procedures,
      with patients treated with cerebrospinal fluid shunts. To perform a cost
      effectiveness analysis, hydrocephalus-related resource consumption and outcome
      (determined as the number of hydrocephalus treatment-free days during follow-up)
      were then retrospectively identified. Cost data were linked to resource use to
      provide a total cost for all resources used. Costs and outcomes were discounted
      annually at 5% by standard economic analysis methods. RESULTS: Twenty-four of 28
      ETV patients had obstructive hydrocephalus. Over equivalent follow-up periods
      (median, 35 mo), the ETV success rate (defined by need for reoperation) was 54%.
      One hydrocephalus-related death and one hemiparesis occurred in the ETV group. No
      permanent procedure-related morbidity or mortality was seen in the shunt group.
      The cost/effect ratios for the two groups were similar. The additional
      incremental resource use by the shunt group included six readmissions and eight
      reoperations. ETV mean costs per patient were $10,570 +/- $7628, versus $10,922
      +/- $8722 for the shunt group (Canadian dollars for the year 2000). Costs accrued
      more quickly for the shunt group as time passed. The additional incremental
      outcome benefit to the endoscopy group was 86 treatment-free days (3.07 d per
      patient [95% confidence interval, -7.56 to 13.70 d]). Neither of these
      differences was statistically significant. CONCLUSION: In this matched cohort,
      ETV was not significantly less costly or more effective over a median 35 months
      of follow-up, with a 54% initial ETV success rate, even before the additional
      morbidity and mortality encountered were taken into account. The time course for
      the accrued costs suggests that a larger cohort, longer follow-up, or higher
      success rates are needed to demonstrate the cost-effectiveness of this therapy.

PMID- 12182438
TI  - Spinal epidural abscesses: clinical manifestations, prognostic factors, and
      outcomes.
AB  - OBJECTIVE: This study was performed to evaluate the clinical manifestations and
      prognostic factors for outcomes among patients with nontuberculous spinal
      epidural abscesses. METHODS: The records and magnetic resonance imaging/computed
      tomographic results for patients treated between 1994 and 2000 were
      retrospectively evaluated. Outcomes were assessed after 11 months, using scores
      ranging from 0 (dead) to 4 (no neurological deficits). RESULTS: All 25 patients
      (mean age, 62 yr) underwent surgery and subsequently received antibiotics.
      Back/neck pain (72% of patients), leukocytosis (64%), fever (60%), and motor
      deficits (56%) were the most common symptoms at admission. Outcomes were assessed
      as poor for 40% of the patients and as good (no deficit or independently
      ambulatory) for 60%. Low leg muscle strength grades (r = 0.68, P < 0.001) and
      high white blood cell (WBC) counts (r = -0.56, P = 0.006) at admission were
      significantly correlated with low outcome scores. From the time of admission
      until 14 days after surgery, the poor-outcome group exhibited significantly (P <
      0.005) higher WBC counts, compared with the good-outcome group. The same was true
      for C-reactive protein levels, with the exception that no differences between
      groups were observed until 8 days after surgery. Factors such as cervicothoracic
      abscess locations (P = 0.041), lower limb motor deficits (P = 0.005), complete
      paralysis (P = 0.005), and WBC counts of more than 14,000 cells/microl (P =
      0.049) at admission were observed to be prognostic for poor outcomes. CONCLUSION:
      Surgical decompression combined with antimicrobial therapy remains the
      recommended treatment. In addition to abscess locations and motor deficits,
      inflammatory markers such as WBC counts and C-reactive protein levels are
      prognostic for outcomes.

PMID- 12182439
TI  - Facet fusion in the lumbosacral spine: a 2-year follow-up study.
AB  - OBJECTIVE: A clinical and radiological follow-up study was undertaken to assess
      the safety, efficacy, and complication rate associated with instrumented facet
      fusion of the lumbar and lumbosacral spine. METHODS: This study involved 99
      patients with degenerative lumbar disorders who were treated surgically at the
      authors' neurosurgical department and followed for more than 2 years. Eighty-two
      patients underwent one-level fusion for the treatment of Grade I or II
      degenerative spondylolisthesis and accompanying spinal canal stenosis (44
      patients) or recurrent disc herniation (38 patients). Seventeen patients
      underwent two-level fusion for the treatment of either double instances of the
      above indications (seven patients) or concurrent stenosis at the adjacent level
      (10 patients). RESULTS: There were no technique-related complications. The
      overall 2-year success rate of fusion was 96%; the success rates by fusion type
      were 99% in one-level fusions and 88% in two-level fusions. Degenerative
      spondylolisthesis had the highest success rate at 100%, whereas the success rate
      in patients who had not responded to previous discectomy was 93%. Patients with
      concurrent stenosis experienced the lowest success rate: 80%. Excellent or good
      clinical results were obtained for 85% of patients with one-level fusions and for
      65% of patients with two-level fusions. CONCLUSION: Instrumented facet fusion
      alone is a simple, safe, and effective surgical option for the treatment of
      patients with single-level disorders, especially patients with degenerative
      spondylolisthesis.

PMID- 12182440
TI  - Comparison of the mini-open versus laparoscopic approach for anterior lumbar
      interbody fusion: a retrospective review.
AB  - OBJECTIVE: The anterior lumbar interbody fusion (ALIF) procedure has become an
      accepted fusion technique for treating patients with degenerative disorders of
      the lumbar spine. Many consider laparoscopic ALIF to be the least invasive
      approach. A modification of the open laparotomy--the "mini-open" approach--is an
      attractive alternative. In this retrospective review, a comparison of these two
      ALIF approaches is presented. METHODS: We conducted a retrospective review of 98
      patients who underwent ALIF procedures between 1996 and 2001 in which either a
      mini-open or a laparoscopic approach was used. Patient demographics,
      intraoperative parameters, length of hospitalization, and technique-related
      complications associated with the use of these two approaches were compared. The
      subset of patients who underwent L5-S1 ALIF procedures was analyzed separately.
      Statistical analysis was conducted with chi2 and Student's paired t tests.
      RESULTS: Between 1996 and 2001, a total of 98 patients underwent ALIF. A
      laparoscopic approach was used in 47 of these patients, and the mini-open
      technique was used in the other 51 patients. Operative preparation and procedure
      time were longer with the use of a laparoscopic approach, and significantly
      greater during L5-S1 ALIF procedures (P < 0.05). A marginal but significant
      increase in length of stay was observed after mini-open ALIF procedures (P <
      0.05). The immediate postoperative complication rate was greater after mini-open
      ALIF procedures, 17.6 versus 4.3% (P < 0.05); however, the rate of retrograde
      ejaculation was higher in the laparoscopic group, 45 versus 6% (P < 0.05).
      CONCLUSION: Both the laparoscopic and mini-open techniques are effective
      approaches to use when performing ALIF procedures. On the basis of the data
      obtained in this retrospective review, the laparoscopic approach does not seem to
      have a definitive advantage over the mini-open exposure, particularly in an L5-S1
      ALIF procedure. In our opinion, the mini-open approach possesses a number of
      theoretical advantages; however, the individual surgeon's preference ultimately
      is likely to be the dictating factor.

PMID- 12182441
TI  - Influence of polarization effects in ooplasma and pronuclei on embryo quality and
      implantation in an IVF program.
AB  - PURPOSE: The presence of a clear half-moon-like zone of cytoplasm in oocytes is
      called "halo effect." The prognostic value of this effect is not yet determined.
      Aligned nucleoli in pronuclei (PN) represent a further polarization phenomenon
      and a marker for implantation potential. Aim of the prospective study was to
      evaluate the influence of the halo effect on IVF outcome and to compare the
      results with observed polarization in PN. METHODS: A total of 374 cycles with
      embryonic transfer were analyzed regarding halo effect and pattern of nucleoli.
      The oocytes were single-cultured to observe the following embryo quality of each
      PN stage. RESULTS: Cycles with halo-positive oocytes showed a significant higher
      pregnancy rate (44.0% vs. 31.1%; p < 0.05). Furthermore, higher pregnancy rates
      in cycles with polarized nucleoli were observed. Polarized PN resulted in a
      significant lower fragmentation and higher cleavage rate of embryos. The
      fragmentation rate was significantly lower in halo+ oocytes, but the cleavage
      rate was not influenced. CONCLUSIONS: The results indicate that the presence of a
      polarized zone of human fertilized oocytes can be a useful indicator for good
      oocyte quality. Since the origin of ooplasmic polarization seems to be a
      different process compared with the alignment of nucleoli, the observation will
      give additional predictive information about the implantation potential.

PMID- 12182442
TI  - Intraindividual hormonal variability in ultrasonographically timed successive
      ovulatory menstrual cycles is detected only in the luteal phase in infertility
      patients.
AB  - OBJECTIVE: To assess intraindividual variation of follicle stimulating hormone,
      luteinising hormone, estradiol, progesterone, inhibin A, and inhibin B in three
      successive ovulatory cycles correlated with transvaginal ultrasound monitored
      morphological changes in the ovary. METHODS: Serial transvaginal color and pulsed
      Doppler ultrasound and serum hormone analysis were performed during
      midfollicular, periovulatory, and midluteal phase for three consecutive cycles in
      19 patients with normal menstrual cycles. RESULTS: Luteinising hormone and
      progesterone showed significant differences in the midluteal phase between the
      1st and 2nd cycle (luteinising hormone p = 0.007 and progesterone p = 0.02).
      Progesterone showed a similar significant change (p = 0.013) between the 2nd and
      3rd cycle. No significant differences were seen in the midfollicular or
      periovulatory phases or between the 1st and 3rd cycle. CONCLUSIONS: Luteal phase
      progesterone and luteinising hormone concentrations showed individual variation
      in successive cycles suggesting early or late corpus luteolysis. Follicular and
      periovulatory hormone levels were similar in subsequent ovulatory cycles.

PMID- 12182443
TI  - Objective assessments of temperature maintenance using in vitro culture
      techniques.
AB  - PURPOSE: To assess the ability of various facets of embryo culture (microscope
      stage warmers, volumes of culture media, culture vessel lids, and type of culture
      incubator) to maintain a constant temperature in vitro. METHODS: Ability to
      maintain 37.0 degrees C in the microenvironment of gametes was recorded by
      digital thermocouple in the chosen facets of in vitro culture. RESULTS: Stage
      warmers are highly variable in their ability to maintain the set temperature
      (range 33.8 degrees C-37.0 degrees C after 60 s). Temperature loss in culture
      media is both volume and vessel dependent, and the direct heat transfer culture
      incubator (MINC) has superior temperature maintenance compared with a large
      volume air convection incubator (FORMA), where temperature regain from 35.0
      degrees C to 37.0 degrees C took 5.5 min compared to >20 min. CONCLUSIONS: There
      are large measurable differences in the ability to maintain set temperature that
      depend on the stage warmer used, volume of media, use of vessel lids, and the
      type of incubator chosen for IVF culture.

PMID- 12182444
TI  - A comparative study of Y chromosome microdeletions in infertile males from two
      Chinese populations.
AB  - PURPOSE: To compare the prevalence and type of Y-microdeletions in Hong Kong and
      Shanghai men with severe male-factor infertility. METHODS: Seven Y-linked
      sequence tagged site (STS) primers and seven gene-specific primers were screened
      in 293 infertile males (139 from Hong Kong and 154 from Shanghai) and 161 fertile
      men (61 from Hong Kong and 100 from Shanghai). Serum FSH, LH, and testosterone
      levels were also measured in these men. RESULTS: The incidence of Yq
      microdeletions in nonobstructive azoospermic men from Hong Kong (8.5%) and
      Shanghai (6%) was similar. Yq microdeletions were observed in severe oligospermic
      patients (8.5%) from Hong Kong but not from Shanghai. Among the 9 Hong Kong men
      with Y-microdeletions, 8 had AZFc deletion and one had AZFb deletion. In
      contrast, 6 of 9 men from Shanghai with Y-microdeletions had AZFb deletion. The
      incidence of AZFb deletion among Y-microdeleted men was statistically different
      between the two populations. Two of the men with AZFb deletion also had AZFa and
      AZFc deletions. CONCLUSIONS: Regional variations in the type of Y-microdeletion
      existed between Hong Kong and Shanghai infertile males.

PMID- 12182445
TI  - Effect of in vivo GnRH agonist and GnRH antagonist on hCG and insulin-stimulated
      progesterone production by human granulosa-lutein cells in vitro.
AB  - PURPOSE: To investigate hCG and insulin-stimulated progesterone (P) production by
      human granulosa-lutein cells (hGLC) in vitro. METHODS: hGLCs were isolated from
      patients undergoing IVF-ET cycles in which GnRH agonist or GnRH antagonist was
      used to prevent a midcycle gonadotropin surge. The cells were cultured for 3
      days, and then treated with hCG 0.5, 1, and 10 IU/I, and insulin 0.01, 0.1, and 1
      microM in serum free conditions. In vitro P production was measured by enzyme
      immunoassay. RESULTS: hCG stimulated P production by hGLCs from cycles in which
      GnRH antagonist was used, but a blunted response was seen in GnRH-agonist treated
      cycles. Insulin-stimulated P production was similar in cells from cycles in which
      GnRH-agonist or GnRH-antagonist treatment was used. CONCLUSIONS: Because insulin
      and hCG may share common pathways beyond the level of receptor activation, we
      hypothesize that GnRH agonist, but not GnRH antagonist, may affect the expression
      and/or activation of LH receptors in the hGLCs.

PMID- 12182447
TI  - Isolation and expression analysis of the human RNH2 gene encoding ribonuclease
      inhibitor 2.
AB  - Ribonuclease inhibitor 1 (RI-1) is a cytoplasmic protein that inhibits a variety
      of pancreatic-type mammalian Rnases by forming a very tight, reversible 1:1
      complex. Recently a novel gene encoding ribonuclease inhibitor 2, Rnh2 has been
      isolated in mouse. The expression pattern of the mouse Rnh2 is specific to
      testis, especially in the spermatogonia. Then it has been suggested that the
      mouse Rnh2 gene may play critical roles in mouse spermatogenesis. In this study,
      we isolated the human RNH2 cDNA and analyzed its expression pattern. The human
      RNH2 is also expressed limited to testis, and then it is suggested that the human
      Rnh2 gene may also play critical roles in human spermatogenesis.

PMID- 12182446
TI  - Successful delivery following cryopreservation of zygotes produced by in vitro
      matured oocytes retrieved from a woman with polycystic ovarian syndrome-like
      disease: a case report.
AB  - PURPOSE: To estimate frozen zygotes, which developed from in vitro matured
      oocytes retrieved from polycystic ovarian syndrome-like disease. METHODS: Oocyte
      retrieval was performed on Day 15 following withdrawal bleeding. The oocytes were
      incubated for 24 h in TCM-199 maturation medium supplemented with follicle fluid,
      E2, FSH, and hCG. RESULTS: A total of 12 immature oocytes were collected. Seven
      of the 12 oocytes (58.3%) developed to the metaphase-II stage, and subsequently,
      all seven fertilized oocytes were frozen at the pronuclear stage. The remaining
      five oocytes failed to develop to the metaphase-II stage after an additional 24 h
      of incubation. Three of seven cryopreserved oocytes were thawed and developed to
      2-8-cell cleaved stage embryos. The first pregnancy failed. However, the second
      frozen-thawed embryo transfer resulted in the delivery of healthy twins.
      CONCLUSIONS: Successful delivery using frozen zygotes from an anovulatory woman
      with polycystic ovarian syndrome-like disease.

PMID- 12182449
TI  - The intrasplenic circulation of three formulations of the same protein antigen.
AB  - This paper presents a kinetic study of the intrasplenic circulation of three
      formulations of the protein antigen conalbumin including the soluble form and two
      liposomal formulations, one encapsulated in the internal aqueous milieu and one
      surface-linked to the liposomal vehicle. These formulations differ not only in
      their physical status but also in their immunostimulating properties and were
      chosen in an attempt to correlate the movements of antigen in lymphoid tissues
      with the immune response elicited. The presence of conalbumin was followed over a
      period of 21 days using, as a detection system, an antibody that we developed and
      which allows for the visualization of antigenic peptides such as those presented
      at the surface of antigen-presenting cells (APC). The results demonstrate that
      the amount of antigen accessing to the spleen, its time of residency and the
      pathway it follows are all profoundly influenced by the form under which it
      penetrates the immune system. The results also indicate that the marked initial
      preferences of an antigen for either B cells, marginal zone macrophages (MZM) or
      metallophilic macrophages (MM) are of fundamental importance in determining the
      fate of this antigen in the spleen. It is concluded that the exact formulation of
      an antigen is as crucial to the regulation of the immune response as is the
      nature of this antigen. It is further concluded that liposomes can be used
      efficiently to modify the formulation of an antigen and can contribute as such to
      the induction of specific immune functions by driving the antigen towards some
      privileged immune cell populations.

PMID- 12182448
TI  - Reduction of macrophage activation after antioxidant enzymes gene transfer to rat
      insulinoma INS-1 cells.
AB  - BACKGROUND: After transplantation, islet damage occurs through oxidative stress
      and host immune rejection mediated in part by macrophage activation. We
      investigated the influence of the overexpression of catalase (CAT) and Cu/Zn
      superoxide dismutase (Cu/Zn SOD) by rat insulinoma INS-1 beta cells exposed to
      oxidative stress on their viability and murine macrophage activation. METHODS:
      INS-1 cells were infected with adenoviral vectors containing CAT (AdCAT) or Cu/Zn
      SOD (AdSOD) genes. After 72 hours, noninfected and infected INS-1 cells were
      exposed to oxidative stress and their viability was assessed using a colorimetric
      assay. Murine peritoneal exudate macrophages (mPEM) incubated with the
      supernatant of infected and stressed INS-1 cells were tested for chemotaxis and
      cytokine release (TNF-alpha, IL-alpha and IFN-gamma). RESULTS: After infection,
      AdCAT and AdSOD gene transfer protected INS-1 cells from the toxicity of
      different oxidative reagents. The exposure of non-infected INS-1 cells to
      oxidative stress stimulated mPEM chemotaxis. INS-1 cells infection with AdCAT or
      AdSOD reduced significantly mPEM chemotaxis from 2.41 +/- 0.31 to 1.61 +/- 0.17
      and from 2.53 +/- 0.24 to 1.27 +/- 0.14 respectively (n = 5; p < 0.05). Cytokine
      release by mPEM was stimulated after exposure to stressed noninfected INS-1 cell
      supernatant. CAT and Cu/Zn SOD overexpression by infected INS-1 cells decreased
      significantly the release of TNF-alpha from 268.18 +/- 30.18 to 81.40 +/- 23.58
      pg/ml and from 446.96 +/- 75.47 to 20.37 +/- 2.38 pg/ml respectively (n = 6; p <
      0.001). The overexpression of these enzymes also reduced significantly the
      release of IL-1beta and IFN-gamma. CONCLUSIONS: CAT or Cu/Zn SOD gene transfer to
      INS-1 cells preserved them from oxidative damage and reduced the macrophage
      activation induced by these pancreatic cells. Therefore, protection of pancreatic
      beta cells against oxidative injury by antioxidant enzymes gene transfer is an
      effective approach to overcome the deleterious actions of macrophages in
      pancreatic islet transplantation.

PMID- 12182450
TI  - Long term iNOS expression in thoracic lymph nodes of silicotic rats.
AB  - Beside the lung, thoracic lymph nodes are most affected during silicosis. The
      mechanisms leading to enlargement of the lymph nodes and partial activation of
      lymph node cells are still unclear. The present study demonstrates an increase in
      iNOS mRNA expression in the lung draining lymph nodes of rats at 1, 2, and 8
      months following silica exposure. Histopathological analysis revealed that iNOS
      protein was exclusively expressed by macrophages located within the granulomatous
      areas of the enlarged lymph nodes. In contrast, no differences in mRNA expression
      and number of iNOS-positive cells were found in the lungs of silica-exposed and
      non-exposed rats. In vitro experiments showed that silica particles alone did not
      induce NO release in primary alveolar macrophages (AMs) or the alveolar
      macrophage cell line NR8383. However, the addition of interferon (IFN)-gamma led
      to a significant nitric oxide production by primary AMs. NR8383 cells responded
      only when a combination of IFN-gamma and silica particles was applied. These
      results indicate that the macrophage activator IFN-gamma, which has already been
      shown to be expressed at elevated levels by lymphocytes of the silicotic lymph
      nodes, may be responsible for the long-lasting iNOS expression in thoracic lymph
      nodes. Our observations support the hypothesis that the mutual activation of
      lymphocytes and macrophages is a central process in the development of chronic
      silicosis.

PMID- 12182451
TI  - Cloning and characterization of the promoter region of the human CD83 gene.
AB  - Human CD83 (hCD83) is a glycoprotein expressed predominantly on the surface of
      dendritic cells (DC). To get insight into the regulation of hCD83 expression, we
      cloned a 3037 bp fragment up-stream of the translation initiation codon. Deletion
      mutants were constructed revealing highest promoter activity in the -261 fragment
      containing four SP1 binding sites and one NF-kappaB element. Electrophoretic
      mobility shift assays demonstrated the specific interaction of NF-kappaB factors
      with the NF-kappaB element as well as specific binding of SP1 and SP3 to the SP1
      binding site. The hCD83 promoter was inducible by TNF-alpha. This inducibility
      was strictly dependent on the intact NF-kappaB element.

PMID- 12182452
TI  - Accessory cells with a veiled morphology and movement pattern generated from
      monocytes after avoidance of plastic adherence and of NADPH oxidase activation. A
      comparison with GM-CSF/IL-4-induced monocyte-derived dendritic cells.
AB  - Veiled cells (VC) present in afferent lymph transport antigen from the periphery
      to the draining lymph nodes. Although VC in lymph form a heterogeneous
      population, some of the cells clearly belong on morphological grounds to the
      Langerhans cell (LC)/ dendritic cell (DC) series. Here we show that culturing
      monocytes for 24 hrs while avoiding plastic adherence (polypropylene tubes) and
      avoiding the activation of NADPH oxidase (blocking agents) results in the
      generation of a population of veiled accessory cells. The generated VC were
      actively moving cells like lymph-borne VC in vivo. The monocyte (mo)-derived VC
      population existed of CD14(dim/-) and CD14(brighT) cells. Of these the CD14(dim/
      ) VC were as good in stimulating allogeneic T cell proliferation as immature DC
      (iDC) obtained after one week of adherent culture of monocytes in granulocyte
      macrophage-colony stimulating factor (GM-CSF)/interleukin (IL)-4. This
      underscores the accessory cell function of the mo-derived CD14(dim/-) VC.
      Although the CD14(dim/-)VC had a modest expression of the DC-specific marker CD83
      and were positive for S100, expression of the DC-specific markers CD1a, Langerin,
      DC-SIGN, and DC-LAMP were absent. This indicates that the here generated
      CD14(dim/-) VC can not be considered as classical LC/DC. It was also impossible
      to turn the CD14(dim/-) mo-derived VC population into typical DC by culture for
      one week in GM-CSF/IL-4 or LPS. In fact the cells died tinder such circumstances,
      gaining some macrophage characteristics before dying. The IL-12 production from
      mo-derived CD14(dim/-) VC was lower, whereas the production of IL-10 was higher
      as compared to iDC. Consequently the T cells that were stimulated by these mo
      derived VC produced less IFN-gamma as compared with T cells stimulated by iDC.
      Our data indicate that it is possible to rapidly generate a population of
      CD14(dim/-) veiled accessory cells from monocytes. The marker pattern and
      cytokine production of these VC indicate that this population is not a classical
      DC population. The cells might earlier be related to the veiled macrophage-like
      cells also earlier described in afferent lymph.

PMID- 12182453
TI  - Modulation of Ly49 D expression after allogeneic bone marrow transplantation and
      functional consequences.
AB  - Ly49 antigens, interacting with MHC class I molecules, enable NK cells to
      distinguish "self" from "non-self". Here, we investigated the activating receptor
      Ly49 D after allogeneic bone marrow transplantation (BMT). After transplantation
      of B6 bone marrow (BM) into BALB/c recipients we observed a significant reduction
      of Ly49 D+ NK cells and a decreased density of expression. We found a
      nonstochastic distribution of Ly49 D with Ly49 G2. In contrast to reduced
      coexpression with Ly49 A, a constant rate of Ly49 G2 on Ly49 D+ NK cells was
      observed in allogeneic chimeras. Cytotoxicity was reduced during the first two
      months after BMT After this time allogeneic chimeras showed tolerance against
      host-specific targets. We conclude that NK cells are able to shape their Lys49
      repertoire fitting to a new environment after allogeneic BMT. This alteration
      seems to depend on the presence of new corresponding MHC class I molecules
      resulting in downregulation of respective receptors on donor cells. Analysing
      coexpression of Ly49 D and Ly49 G2, we found a relationship between these two
      receptors, showing a distinct effect after allogeneic BMT. Functional data
      indicate that a time of reduced NK cell cytotoxicity after BMT is followed by in
      vitro tolerance of allogeneic chimeras.

PMID- 12182454
TI  - Analysis of the immune response against tetanus toxoid: enumeration of specific T
      helper cells by the Elispot assay.
AB  - Tetanus toxoid (TT) is an antigen known to induce strong T cell specific immune
      responses in humans after vaccination. Here we have used the Elispot assay to
      assess the number of TT-specific Interferon-gamma (IFN-gamma) secreting T cells
      present in individuals and monitored the number of TT specific T cells present in
      the donors for more than two years. In each of the 22 healthy volunteers tested,
      TT-specific T cells could be detected. Six out of 7 repetitively tested donors
      showed a remarkably constant number of TT-specific IFN-gamma secreting T cells
      over several months, whereas one donor demonstrated a transient increase during a
      flu-like infection. Three healthy donors received TT booster-immunizations and
      showed significant increases in the number of TT-specific IFN-gamma secreting T
      cells which reached peak levels by 4 weeks after vaccination. Depletion of either
      CD4+ T cells, CD8+ T cells or CD16+/CD56+ T cells by immunomagnetic separation
      demonstrated that TT-specific IFN-gamma secretion is mediated exclusively by CD4+
      T cells. In addition, HLA class-I and -II blocking studies showed that IFN-gamma
      production is performed by HLA class-II restricted cells. Our data show that the
      Elispot assay can be reliably used to assess the number of TT-specific CD4+ IFN
      gamma producing cells (i.e. probably T helper cells) and therefore maybe also
      useful for the assessment of reactions to other helper antigens.

PMID- 12182456
TI  - B-1 B cell subset composition of DBA/2J mice.
AB  - Studies of B cell subpopulations have focused upon BALB/c mice and related
      strains. The B cell subset composition of DBA/2J mice, a prototype strain for
      BALB/c mice, has been investigated less thoroughly. This report provides the
      results of a study of the B-1 B cells of DBA/2J mice. In contrast to C.B-17 mice,
      in which B-1 B cells expressed both the CD5 and CD11b antigens, CD11b expression
      was most characteristic of DBA/2J B-1 B cells. This was particularly evident in
      the peritoneal cavity where CD5-CD11b+ B cells were the predominant B cell
      subpopulation. The number of B-1 B cells increased with age in both the spleen
      and peritoneal cavity. Strain-specific differences in B cell subset composition
      may be significant when considering B cell lymphomagenesis with aging.

PMID- 12182455
TI  - Influence of porcine natural modified surfactant on chemotaxis and oxidative
      metabolism of polymorphonuclear leukocytes.
AB  - Surfactant has been shown to influence a variety of immune functions. However,
      for in vitro studies most investigators used a single surfactant concentration
      often far below what has to be expected in bronchoalveolar fluid following
      surfactant replacement therapy. We studied the chemotactic activity and the
      oxygen metabolite release of human polymorphonuclear leukocytes (PMN) following
      incubation with Curosurf, a porcine modified natural surfactant preparation, at
      concentrations ranging from 1 to 16 mg/ml. In the presence of 1% bovine serum
      albumin, surfactant at 1 and 4 mg/ml enhanced anaphylatoxin C5a-related
      chemotaxis, whereas a higher dose of 16 mg/ml was inhibitory. Furthermore,
      Curosurf itself demonstrated a concentration-dependent chemotactic effect. Oxygen
      metabolite release, as measured by nitroblue tetrazolium reduction, was
      significantly diminished at surfactant concentrations of 8 and 16 mg/ml. This
      effect was most pronounced when group B streptococci at concentrations 5 x 10(9)
      CFU/ml were applied for PMN stimulation. We conclude that the effects of
      surfactant on PMN immune functions are not only concentration-dependent but also
      influenced by the degree of PMN stimulation.

PMID- 12182457
TI  - The course of Leishmania major infection in mice lacking granzyme-mediated
      mechanisms.
AB  - We previously showed that T cells expressing granzyme (gzm) A are more frequent
      in skin lesions of susceptible mice than in those of resistant mice infected with
      the intracellular parasite Leishmania major. To determine the in vivo role of gzm
      in cutaneous leishmaniasis, we examined the course of L. major infection in gzmA
      deficient mice. Despite a delay in host colonization of susceptible mice, the
      lack of gzmA did not influence the course of lesion development or result in a
      discernible alteration of the interferon-gamma and interleukin-4 production.
      Moreover, no differences in these parameters were observed between wild-type
      controls and mice deficient in gzmB or both gzmA and gzmB. These findings
      indicate that neither gzmA nor gzmB are critical for the development of T helper
      cell responses and the outcome of L. major infection.

PMID- 12182458
TI  - IL-24 is expressed by rat and human macrophages.
AB  - Recently, a number of interleukin-10 (IL-10) homologues, among them IL-24
      formerly known as melanocyte differentiation factor-7 (mda-7), has been
      described. Since IL-10 is released by macrophages and plays an important role in
      the resolution of inflammatory processes, we hypothesized that IL-24 might also
      be expressed in cells of the monocyte/macrophage lineage. We analyzed IL-24
      expression on the mRNA and protein level in stimulated rat and human macrophages.
      In rat alveolar macrophages and NR8383 cells, IL-24 mRNA induction was observed
      following stimulation with LPS and IL-4 whereas TNF-alpha failed. Intracellular
      IL-24 protein was detected in unstimulated and IL-4 stimulated NR8383 cells. Also
      human blood monocytes showed a strong up-regulation of IL-24 mRNA following
      preparation which was enhanced by LPS and lowered by IL-10. Furthermore,
      infection of human monocytes with influenza A virus A/PR/8 caused an induction of
      IL-24 mRNA expression. In conclusion, our data show that IL-24 expression is
      induced in stimulated and infected rat and human macrophages, however, more
      insights into the functions of IL-24 are necessary to define its physiological
      relevance.

PMID- 12182460
TI  - Natural anti-galactose alpha1,3 galactose antibodies delay, but do not prevent
      the acceptance of extracellular matrix xenografts.
AB  - Naturally occurring antibodies to the galactose alpha1,3 galactose (alpha gal)
      epitope expressed on xenogeneic grafts are a major barrier to organ
      transplantation in humans. Porcine small intestinal submucosa (SIS) expresses the
      alpha gal epitope and is currently being used as a bioscaffold for tissue
      remodeling. To examine in detail the potential role of the alpha gal epitope in
      immune recognition of this acellular, avascular biomaterial, we have used mice
      which have a genetic disruption in the alpha1,3 galactosyltransferase gene (alpha
      gal(-/-)mice) and thus express natural anti-alpha gal antibodies in a manner
      similar to humans. It was found that alpha gal(-/-)mice produced IgM anti-alpha
      gal antibodies in addition to IgG1 SIS-specific antibodies, which did not bind to
      the alpha gal epitope. Histological examination of implant sites demonstrated an
      early inflammatory response that consisted predominantly of neutrophils in both
      alpha gal(+/+) and alpha gal(-/-)mice. However, while alpha gal(+/+)mice
      completely remodeled SIS implants by day 25, alpha gal(-/-)mice still exhibited
      some visible SIS together with inflammatory cellular infiltrates at this time
      point. Nevertheless, by day 35, the implant site in alpha gal(-/-)mice appeared
      to be entirely remodeled although a few acute inflammatory cells were still
      present. Immunization of alpha gal(-/-)mice with sheep erythrocytes to enhance
      anti-alpha gal antibody levels led to a more robust early inflammatory response
      following implantation but did not change the ultimate fate of the graft. We
      conclude that, in contrast to xenotransplantation of whole organs, naturally
      occurring anti-alpha gal antibodies do not influence the ability of xenogeneic
      extracellular matrices to serve as bioscaffolds for tissue remodeling.

PMID- 12182459
TI  - Novel assays of multiple lymphocyte functions in whole blood measure: new
      mechanisms of action of mycophenolate mofetil in vivo.
AB  - The antiproliferative effects of MMF are believed to be the mechanism of its
      immunosuppressive action. We further investigated the mechanisms of action by
      assessing the pharmacodynamics (PD) of MMF in treated animals using whole blood
      assays not only of lymphocyte proliferation but also of activation. In vitro,
      different MPA concentrations were added to rat whole blood. In vivo, Lewis rats
      were treated with single doses of 5, 10 or 20 mg/kg MMF (n = 6 rats/dose group).
      Blood was obtained before and at different times after drug administration. For
      both in vitro and in vivo studies, different mitogens with calcium-dependent
      (TCR) or -independent (co-stimulatory) pathways of lymphocyte activation were
      added to the blood for stimulation. Proliferation was measured by [3H]TdR
      incorporation and by flow cytometric detection of DNA content. Activation was
      measured by changes in T cell surface expression of CD25, CD134, CD71, CD11a and
      CD54. In vitro and in vivo studies showed a dose-dependent inhibition by MPA and
      MMF, respectively, of lymphocyte proliferation and surface antigen expression. We
      observed high correlations between MMF PD effects over time with both MMF dose
      and MPA plasma concentrations in vivo. We show that MMF, apart from its
      antiproliferative effect, induced a dose-dependent suppression of calcium
      dependent and -independent stimulated expression of important lymphocyte cell
      surface antigens. These data suggest that the ex vivo assessment of immune
      function in whole blood can uncover new mechanisms of MMF action. Our results
      demonstrated that the measurement of the PD is a means to assess the functional
      effects of MMF after its administration in vivo.

PMID- 12182461
TI  - Allogeneic chimerism established with a mixture of low dose bone marrow cells and
      splenocytes in sublethally irradiated mice.
AB  - BACKGROUND: Allogeneic chimerism has been established in graft-accepting
      recipients and the donor cells in the host may act in a major way to facilitate
      the induction of tolerance. In this study, we examined the effects of allogeneic
      chimerism after injecting donor bone marrow cells (BMCs) mixed with splenocytes
      (SPLCs) to the sublethally conditioned recipients. METHODS: In BALB/c(H-2(d)) to
      B6(H-2(b)) combination, B6 recipients were irradiated at 7.5 Gy and were injected
      a mixture of donor BMCs and SPLCs intravenously. On day 90 after injection, the
      degree of chimerism in peripheral blood lymphocytes (PBL) and in the splenocytes
      was checked by flow cytometry. RESULTS: In groups which were injected varying
      BMCs, when > 45 x 10(6) BMCs were injected into B6, a large percentage of donor
      cells were detected in PBL and in the spleen. In contrast, when < 30 x 10(6) BMCs
      were injected into B6, only a small percentage of donor cells were detected. In
      the groups which were injected 3 x 10(6) BMCs with varying SPLCs, when > 10 x
      10(6) SPLCs were added, a large percentage of donor cells were detected in PBL
      and SPLCs, but a small percentage of donor cells were detected with the addition
      of < 3 x 10(6) SPLCs. A high percentage of chimeric mice showed donor specific
      tolerance in vitro, mixed lymphocyte responses, and in vivo, skin grafting. In
      contrast, only a small percentage of chimeric mice showed no donor specific
      tolerance by skin grafting. CONCLUSION: These findings suggested that even a low
      dose of BMCs can establish a state of allogeneic chimerism and donor specific
      tolerance if combined with SPLCs.

PMID- 12182462
TI  - Quantification of lymphocytes propagating from rat-kidney allografts--a tool to
      monitor anti-rejection treatment.
AB  - BACKGROUND: Morphological evaluation of kidney biopsies applying the Banff
      Classification is closely correlated to clinical parameters of rejection.
      However, this classification is insufficient for monitoring the effect of
      instituted anti-rejection therapy. The objective of the present study was to
      develop a diagnostic tool enabling rapid assessment of the effects of an
      attempted anti-rejection treatment. MATERIALS AND METHODS: A kidney
      allotransplantation model in the rat was applied. All animals were initially
      maintained on cyclosporine A (CsA). In order to induce an episode of acute
      cellular rejection, CsA was withdrawn for 5 days. Thereafter, the
      immunosuppressive treatment was restarted. Core biopsies were taken before, and
      at various times after, the introduction of anti-rejection therapy. Infiltrating
      cells were isolated using an in vitro culture system, allowing cells to propagate
      from the biopsies to culture medium. Propagated cells were counted and analysed
      for subtype and activation markers using flow cytometry. The results were
      compared with immunohistochemical and morphological analyses of the grafts.
      RESULTS: By applying the in vitro culture system it was possible to demonstrate a
      reduction in outgrowth of mononuclear cells from core biopsies as early as 2 days
      after the start of anti-rejection therapy. At this time-point, as well as 2 days
      later, morphological and immunohistochemical analyses of biopsies showed ongoing
      acute cellular rejection, with no differences between biopsies taken before and
      after restart of CsA-therapy. The percentage of propagating T lymphocytes
      expressing the activation markers CD25 or MHC class II did not differ between
      grafts with ongoing rejection and grafts obtained from CsA-treated rats, neither
      did the ratio of CD4/CD8-positive cells. CONCLUSION: Our findings indicate that
      the ex vivo propagation method could function as a complement to routine
      histology, not only in the diagnosis of cellular rejection but also in order to
      rapidly reveal a failure of an anti-rejection therapy to halt the rejection
      process.

PMID- 12182463
TI  - Efficacy of donor splenocytes mixed with bone marrow cells for induction of
      tolerance in sublethally irradiated mice.
AB  - BACKGROUND: High dose of bone marrow cells (BMCs) has been reported to be
      essential to establish donor-specific tolerance. In clinical settings, a large
      quantity of BMCs is very difficult to be obtained. Our previous report
      demonstrated that even a low dose of BMCs could establish donor-specific
      tolerance if mixed with splenocytes (SPLCs). In the present study, various
      components of SPLCs were purified or removed and were investigated their
      contribution for enhancement of bone marrow engraftment leading to donor-specific
      tolerance in sublethally irradiated mice. METHODS: Sublethally irradiated C57BL/6
      recipient mice were intravenously injected 3 x 10(6) BMCs mixed with various
      components and various numbers of SPLCs harvested from BALB/c donor mice. One
      week after injection, skin grafting was performed. The degree of chimerism in
      peripheral blood lymphocytes (PBLs) and in SPLCs was analyzed by FACS 3 months
      after transplantation. RESULTS: Recipients receiving 3 X 106 BMCs mixed with 10 x
      10(6) T cell-enriched SPLCs established chimerism. Recipients receiving BMCs
      mixed with macrophage-depleted SPLCs also showed chimeirism and donor-specific
      tolerance. B cell-enriched SPLCs did not help small dose of BMCs to establish
      chimerism. Irradiated SPLCs were not effective to induce tolerance even with
      additional infusion to recipients. CONCLUSIONS: Active effects of splenic T cells
      were more important to help engraftment of small dose of BMCs than B cells, but
      the interaction between T and B cells might play some roles to enhance BMC
      engraftment. Splenic macrophages or dendritic cells might have some adverse
      effects against tolerance induction. Fatal graft-versus-host disease (GVHD) might
      be avoided by depleting adherent cells from SPLCs, so macrophages or dendritic
      cells were also considered as key components to induce donor-specific tolerance
      and prevent GVHD in this model.

PMID- 12182464
TI  - No association between transforming growth factor beta gene polymorphism and
      acute allograft rejection after cardiac transplantation.
AB  - Transforming growth factor-beta1 (TGF-beta1) is a multifunctional cytokine, which
      inhibits both development of Th1 and Th2 subsets and the Th1 proinflammatory
      response. TGF-beta1 production is influenced through several single nucleotide
      polymorphisms (SNP) in the structural gene and promoter region. Acute rejection
      of transplants depends on the Th1/Th2 balance within the graft, high levels of
      TGF-beta1 shift this balance towards Th2. We investigated whether genotypes of 4
      SNP (-800 and -509 in the promoter region, codon 10 and codon 25 in the first
      exon) were correlated with cardiac disease or with incidence of rejection after
      heart transplantation (HTX). Genotypes were determined for 70 HTX patients and 61
      donors by sequencing or oligonucleotide ligation assay. No association between
      SNP genotypes and heart disease or acute transplant rejection was observed. We
      conclude that genetic variation in the TGF-beta1 gene neither influences the
      existence of cardiomyopathy nor the incidence of rejection upon HTX.

PMID- 12182465
TI  - Short-course methotrexate and long-term acceptance of fully allogeneic rat
      cardiac grafts: a possible mechanism of tolerance.
AB  - Although a short course of methotrexate (MTX) has a potential immunoregulatory
      effect on clinical allograft rejection, little data are available about the drug,
      and the mechanism of hyporeactivity after withdrawal is still unknown. In
      previous studies, we achieved permanent graft acceptance through administration
      of a short course of high-dose MTX during heterotopic ratheart transplantation
      (HHT) in a combination of DA (MHC haplotype; RT1(a)) to PVG/c (RT1(c)) rats. A 3
      week course of MTX (0.25 mg/kg/day) was administered intraperitoneally to the
      PVG/c recipients of a DA heart graft, and 11 of 16 rats survived longer than 300
      days after HHT. The splenic lymphocytes obtained from one recipient showed high
      reactivity against donor type splenic lymphocytes, but others did not. All serum
      samples from recipients showed immunosuppressive activity. The serum had anti
      donor antibodies. These results showed that tolerance induced by short-course MTX
      was maintained by a serologic factor believed to be anti-idiotypic antibodies.

PMID- 12182468
TI  - Pancreatic tissue grafts are reinnervated by neuro-peptidergic and cholinergic
      nerves within five days of transplantation.
AB  - The reinnervation process is crucial for the survival and functioning of cell,
      tissue or organ transplants. This study was designed to examine the exact time of
      reinnervation of intraocular pancreatic tissue transplants in rats. The rate of
      survival of neuropeptide-containing cells in pancreatic tissue grafts was also
      investigated. Calcitonin gene-related peptide (CGRP), galanin (GAL), neuropeptide
      Y (NPY) were observed in the surviving nerve cell bodies of the grafts. The
      iridal nerves reinnervating the pancreatic grafts expressed CGRP, GAL, NPY and
      choline-acetyl-transferase (ChAT) on day 5, and tyrosine hydroxylase (TH) and
      nitric oxide synthase (bNOS) on day 6 of the transplantation period. The
      expression of CGRP in the reinnervating nerves was more consistent when compared
      to GAL, NPY, ChAT, TH and bNOS. Although all of the three neuropeptides (CGRP,
      GAL, NPY) were present in the surviving nerve cell bodies of the pancreatic
      tissue graft up to the end (day 9) of the transplantation period, the number of
      CGRP-immunopositive cells was consistently higher throughout the transplantation
      period. Hence, the number of CGRP-positive cells in the pancreatic tissue graft
      was significantly (P < 0.05) higher than that of GAL and NPY. In conclusion,
      pancreatic fragments were reinnervated by neuropeptidergic (CGRP, NPY) and
      cholinergic (ChAT) nerves within the first 5 days of transplantation. In addition
      to the reinnervation of pancreatic tissue grafts, the intrinsic neurones of the
      grafts also survived after transplantation. The rate of survival of CGRP
      containing cells in the pancreatic tissue grafts was more consistent compared to
      that of NPY and GAL.

PMID- 12182469
TI  - Inhibition of the IL-15 pathway in anti-CD25 mAb treated renal allograft
      recipients.
AB  - Anti-CD25 mAb's are used for prophylaxis of rejection in allograft
      transplantation. These agents target the alpha-chain, part of the IL
      2Ralphabetagamma complex. The beta- and gamma-chain are signaling components that
      are not specific for IL-2. The T-cell growth factors IL2, IL-7 and IL-15 utilize
      the gamma-chain and IL-2 and IL-15 share the beta-chain. We have studied the
      consequences of targeting the IL-2R alpha-chain with the anti-CD25 mAb
      basiliximab by measuring the IL-2R alphabetagamma expression levels and the IL-2,
      IL-7 and IL-15 driven proliferation. By flowcytometry and limiting dilution
      analysis, the IL-2R complex was analyzed in peripheral blood samples from renal
      allograft recipients (n = 29) who received basiliximab (20 mg IV bolus on day 0
      and 4), cyclosporin and mycophenolate mofetil. In peripheral blood, after
      induction therapy with basiliximab, no CD25 positive T-cells were detectable for
      61 days (median, range 25-93 days). When CD25 cells were covered with
      basiliximab, the percentage and the mean fluorescence intensity (MFI) of IL
      2Rbeta positive T-cells significantly decreased, P = 0.02 and P = 0.013,
      respectively, whereas the expression level of the IL-2Rgamma was not affected.
      The inhibition of the expression of the IL-2R alpha- and beta-chain had
      significant consequences for the function of these cells. Both the IL-2- and the
      IL-15-dependent proliferation were inhibited, P = 0.007 and P = 0.01,
      respectively. The control, the IL-7 driven proliferation, was not influenced by
      basiliximab. In conclusion, therapy with anti-CD25 mAb's affect T-cell-dependent
      allogeneic immune responses, not only by blocking IL-2 signaling but also by
      impairing IL-15 signaling through downregulating the IL-2/IL-15 receptor beta
      chain.

PMID- 12182467
TI  - Remission and pancreas isograft survival in recent onset diabetic NOD mice after
      treatment with low-dose anti-CD3 monoclonal antibodies.
AB  - Diabetes in NOD mice is an autoimmune disease similar to Type I diabetes in
      humans. Prior to hypoglycemia, changes in the islet infiltrate led to
      autoreactive T cell activation and destruction of the insulin-producing beta
      cells. If T cell activation can be inhibited before beta cell destruction is
      complete, islet cell rescue and regeneration can occur. Female NOD mice > 100
      days old with blood glucose levels > 20 mM/l for less than 7 days were selected
      as 'recent onset' mice. Untreated, all of these animals would die of diabetes in
      < 40 days. Mice treated with anti-CD4 (GK1.5) achieved 14.3% permanent remission,
      while those treated with anti-CD8 (53.6.7) showed 33.3% permanent remission. Mice
      treated with anti-CD3 (145-2C1) also achieved 33.3% permanent remission, but 14%
      of these died of first dose syndrome. In mice treated with a low dose of anti-CD3
      (10 microg KT3), which did not induce first dose syndrome, 50% remained in
      remission for > 100 days. This dose of mAb reduced insulitis but did not deplete
      splenic CD3 cells. When mice in remission were challenged with a vascularized
      pancreas isograft at 50 days, 9/22 remained normal and 13/22 had recurrent
      disease in both transplanted and native pancreas. Of the long-surviving isografts
      7/9 were in KT3 treated recipients. Histology showed activated T cell
      infiltration in the native and transplanted pancreases of mice with transient
      remission. Benign insulitis with macrophages, B cells, CD4 > CD8 T cells and low
      levels of IL-2R, IL-2, IFN-gamma and IL-4 was seen in islets from the native
      pancreas and in long surviving pancreas isografts in mice that remained in
      remission. Thus, using low dose KT3, it was possible to halt the development of
      diabetes in 50% of animals treated soon after diagnosis, despite significant
      islet cell destruction at this stage. Of the KT3 treated mice in permanent
      remission, 70% had re-established tolerance to autoantigen and did not destroy
      vascularized pancreas isografts.

PMID- 12182470
TI  - Inactivation of Escherichia coli O157:H7, Salmonella enterica serotype
      enteritidis, and Listeria monocytogenes on lettuce by hydrogen peroxide and
      lactic acid and by hydrogen peroxide with mild heat.
AB  - Iceberg lettuce is a major component in vegetable salad and has been associated
      with many outbreaks of foodborne illnesses. In this study, several combinations
      of lactic acid and hydrogen peroxide were tested to obtain effective
      antibacterial activity without adverse effects on sensory characteristics. A five
      strain mixture of Escherichia coli O157:H7, Salmonella enterica serotype
      Enteritidis, and Listeria monocytogenes was inoculated separately onto fresh-cut
      lettuce leaves, which were later treated with 1.5% lactic acid plus 1.5% hydrogen
      peroxide (H2O2) at 40 degrees C for 15 min, 1.5% lactic acid plus 2% H2O2 at 22
      degrees C for 5 min, and 2% H2O2 at 50 degrees C for 60 or 90 s. Control lettuce
      leaves were treated with deionized water under the same conditions. A 4-log
      reduction was obtained for lettuce treated with the combinations of lactic acid
      and H2O2 for E. coli O157:H7 and Salmonella Enteritidis, and a 3-log reduction
      was obtained for L. monocytogenes. However, the sensory characteristics of
      lettuce were compromised by these treatments. The treatment of lettuce leaves
      with 2% H2O2 at 50 degrees C was effective not only in reducing pathogenic
      bacteria but also in maintaining good sensory quality for up to 15 days. A < or =
      4-log reduction of E. coli O157:H7 and Salmonella Enteritidis was achieved with
      the 2% H2O2 treatment, whereas a 3-log reduction of L. monocytogenes was
      obtained. There was no significant difference (P > 0.05) between pathogen
      population reductions obtained with 2% H2O2 with 60- and 90-s exposure times.
      Hydrogen peroxide residue was undetectable (the minimum level of sensitivity was
      2 ppm) on lettuce surfaces after the treated lettuce was rinsed with cold water
      and centrifuged with a salad spinner. Hence, the treatment of lettuce with 2%
      H2O2 at 50 degrees C for 60 s is effective in initially reducing substantial
      populations of foodborne pathogens and maintaining high product quality.

PMID- 12182466
TI  - CTLA4Ig combined with anti-LFA-1 prolongs cardiac allograft survival
      indefinitely.
AB  - CTLA4Ig and anti-LFA-1 are members of a new generation of immunomodulatory drugs
      which inhibit important signaling pathways in T cell activation. Both substances
      target molecules which have pivitol functions in the activation of CD4+ and CD8+
      T cells and have been theorized to have an interdependent relationship. These
      drugs have been used independently in various treatment regimens and have shown
      great promise in prolonging the survival of allografts. In order to test whether
      these substances have synergistic or potentiating effects when combined, we
      performed mixed lymphocyte reactions, skin transplantation and vascularised
      heterotopic heart transplantation in the Balb/c (H-2(d)) to C3H/HeJ (H-2(k))
      strain combination. When anti-LFA-1 and CTLA4Ig were combined at low doses, there
      was a substantial inhibition of lymphocyte proliferation. When each drug was used
      as a mono-therapy in skin graft recipients, there was no significant effect on
      median graft survival (anti-LFA-1, 15 days; CTLA4Ig, 16 days) when compared to
      untreated controls (13 days), whereas a combination of anti-LFA-1 and CTLA4Ig
      extended graft survival significantly to 32 days. Untreated vascularised heart
      grafts rejected at a median of 8 days, CTLA4Ig-treated mice rejected at a median
      time of 79 days and anti-LFA-1-treated mice rejected at 43 days (n = 9). When
      CTLA4Ig and anti-LFA-1 were combined, all animals had functioning heart grafts at
      100 days after transplantation. Histological analysis of combined-therapy hearts
      showed no signs or only minor changes associated with chronic rejection. In
      conclusion, these results indicate a synergistic effect of combining anti-LFA-1
      with CTLA4Ig in inhibiting lymphocyte proliferation and prolonging the survival
      of fully MHC-mismatched allografts.

PMID- 12182471
TI  - Consumer acceptance of fresh-cut iceberg lettuce treated with 2% hydrogen
      peroxide and mild heat.
AB  - An antibacterial treatment consisting of 2% hydrogen peroxide at 50 degrees C for
      60 s was evaluated for its effects on the sensory quality of fresh-cut iceberg
      lettuce. Treated lettuce was packaged in polyethylene film by a protocol used in
      the fresh-cut produce industry and then stored along with untreated controls for
      3, 10, and 15 days at 5 degrees C. Gas chromatographic analysis confirmed that
      the desired initial volume (approximately 6 liters) and oxygen gas content
      (approximately 10%) were maintained during storage. Consumers from the local
      community who were the primary shoppers for their households and who purchased
      and ate lettuce regularly evaluated the appearance, color, aroma, flavor, and
      texture of the lettuce and their overall liking of the lettuce. Forty consumers
      were recruited to evaluate processing replication 1 on 26 April, and another 40
      were chosen to evaluate processing replication 2 on 3 May. Because replication
      differences were observed in instrumental color measurements and in mean sensory
      ratings, replications were not pooled for the two test dates. Lettuce purchased
      for processing replication 2 was considerably greener than that used in
      replication 1. Overall, the antibacterial treatment was more effective than the
      control treatment in maintaining sensory quality over 15 days of storage,
      provided that the lettuce was initially intensely green. Three-fourths of the
      participants indicated that they would be willing to buy precut packaged lettuce
      that had already been treated at the packinghouse or processing plant with an
      antibacterial solution, and of these participants, 62.5% indicated that they
      would be willing to pay 5 to 10 cents more per bag.

PMID- 12182472
TI  - Application of nested polymerase chain reaction to detection of Salmonella in
      poultry environment.
AB  - Isolation of Salmonella from environmental and processing-plant poultry samples
      requires the sampling of large numbers of areas within the poultry house or
      plant. Subsequently, the required number of samples necessitates a large volume
      of work for a microbiology laboratory, especially when the protocol requires the
      inclusion of a delayed secondary enrichment for the isolation of Salmonella. This
      study examined the use of the polymerase chain reaction (PCR) to identify those
      secondary enrichments containing Salmonella. The unique Salmonella virulence gene
      invA was chosen as the target for the development of a nested PCR because of its
      uniform distribution among Salmonella serotypes. The use of nested PCR primers
      increased the sensitivity of detection 100-fold, resulting in the detection of as
      few as four cells. There was a strong, statistically significant positive
      correlation between PCR and culture results as determined by chi-square (P <
      0.001) and kappa (kappa = 0.915; excellent agreement) tests. Using PCR to screen
      primary enrichments for presumptive Salmonella contamination, we improved our
      efficiency at isolating Salmonella upon secondary enrichment by 20%, and no false
      negatives were observed. This method will not only validate the use of secondary
      enrichment procedures but also reduce costs and manpower required for the
      surveillance of Salmonella.

PMID- 12182473
TI  - Occurrence and distribution of Arcobacter species in poultry processing.
AB  - A total of 16 broiler flocks slaughtered in the morning in eight Belgian poultry
      slaughterhouses were examined for the presence of Campylobacteraceae. In samples
      collected before and after chilling, the prevalence of arcobacters was found to
      be higher than the prevalence of thermophilic campylobacters, with the slaughter
      procedure used having no clear effect. Two slaughterhouses were selected for a
      detailed investigation of the occurrence and distribution of arcobacters.
      Sampling carried out before slaughter revealed that both Arcobacter butzleri and
      Arcobacter cryaerophilus were commonly present on the slaughter equipment in both
      plants. These findings indicate inadequate decontamination of the slaughterhouse
      environment and suggest potential Arcobacter contamination of broiler carcasses
      through the slaughter equipment. Even before evisceration, contamination levels
      of hundreds to several thousands of arcobacters per gram of neck skin were
      detected. It appears unlikely that contamination through slaughter equipment
      alone explains the high contamination levels found for poultry products.
      Arcobacters were not isolated from the 30 intestinal tracts sampled for each
      broiler flock examined. A. cryaerophilus was the only Arcobacter species
      recovered from the transport crate samples collected before and after washing.
      Arcobacter contamination during slaughter, either direct (from chicken intestinal
      content or feces) or indirect (from equipment), was not confirmed. The origin and
      the precise routes of contamination remain to be determined.

PMID- 12182475
TI  - Hot water and organic acid interventions to control microbiological contamination
      on hog carcasses during processing.
AB  - Pork skin and muscle tissue were washed with water at temperatures from 25 to 80
      degrees C. Water temperatures of 65 and 80 degrees C resulted in greater
      population reductions of Enterobacteriaceae on pork muscle tissue than lower
      water temperatures. There was no observable effect of water temperature on
      population reductions of Enterobacteriaceae on pork skin. Water temperatures of
      55, 65, and 80 degrees C reduced the populations of Enterobacteriaceae on
      inoculated scalded carcasses processed in a university abattoir by 1 to 1.5
      log/cm2. Following the water wash with an organic acid rinse resulted in further
      numerical reductions in populations, although these were not statistically
      different from the water wash alone. The jowls of both scalded and skinned
      carcasses processed in a commercial establishment were directly inoculated with a
      fecal material slurry and then processed with organic acid rinsing only, hot
      water washing only, or a combination of hot water washing followed by organic
      acid rinsing. The hot water and acid treatment reduced the populations of
      mesophilic aerobic bacteria and Escherichia coli by approximately 2 log cycles on
      both scalded and skinned hog carcasses. The combined treatment resulted in 60% of
      the scalded carcasses and 40% of the skinned carcasses with undetectable levels
      of E. coli after direct fecal inoculation of the carcasses. Hot water washing
      followed by organic acid rinsing can significantly improve the microbiological
      quality of pork carcasses.

PMID- 12182474
TI  - Attachment of Arcobacter butzleri, a new waterborne pathogen, to water
      distribution pipe surfaces.
AB  - The capability of Arcobacter butzleri to attach to various water distribution
      pipe surfaces, such as stainless steel, copper, and plastic, was evaluated using
      scanning electron microscopy. Our results indicated that Arcobacter cells could
      easily attach to all surface types and the number of attached cells depended on
      the length of exposure and temperatures (4 and 20 degrees C). Extracellular
      fibrils were also observed on the stainless steel surface, especially after 72 h
      of contact times at both refrigeration and ambient temperatures. In addition, the
      surface energy value of each material was estimated by contact angle measurements
      using water, alpha-bromonaphthalene, and dimethylsulfoxide. The surface energy of
      A. butzleri was 58.6 mJ x m(-2) and the surface energy values of the three
      surfaces studied showed that plastic had a low energy surface (26.1 mJ x m(-2))
      as did copper (45.8 mJ x m(-2)) and stainless steel (65.7 mJ x m(-2)).

PMID- 12182476
TI  - Inactivation of Escherichia coli by a combination of nisin, pulsed electric
      fields, and water activity reduction by sodium chloride.
AB  - The effect of nisin combined with pulsed electric fields (PEF) and water activity
      reduction by sodium chloride (NaCl) on the inactivation of E. coli in simulated
      milk ultrafiltrate media was studied with a Doehlert design and a response
      surface method. The reduction of water activity from 0.99 to 0.95 by the addition
      of NaCl (without any other hurdle) did not affect E. coli viability of
      approximately 10(8) CFU/ml. A reduction in PEF effectiveness occurred when the
      NaCl concentration was increased because of an increase in conductance, which
      reduced the pulse decay time. In cells submitted to PEF nisin activity was
      decreased, probably as a consequence of the nonspecific binding of nisin to
      cellular debris or the emergence of new binding sites in or from cells. However,
      the lethal effect due to nisin was reestablished and further improved when water
      activity was reduced to 0.95. A synergistic effect was evidenced when low
      intensity PEF were applied. Decreasing water activity to 0.95 and applying PEF at
      5 kV/cm (a nonlethal intensity when no other hurdle is used) with the further
      addition of nisin (1,200 IU/ml) resulted in a 5-log cycle reduction of the
      bacterial population.

PMID- 12182477
TI  - Assessment of the potential for Listeria monocytogenes survival and growth during
      alfalfa sprout production and use of ionizing radiation as a potential
      intervention treatment.
AB  - Alfalfa seeds (Australian, nondormant, nonscarified) were treated with 20,000 ppm
      active chlorine, sprouted in canning jars for 5 days, and packaged and stored at
      5 degrees C for up to 9 days. Seeds or sprouts were inoculated with a three
      strain cocktail of Listeria monocytogenes at one of three points during the
      process-day 0 (before 24-h aqueous seed soak), day 1 (after 24-h aqueous seed
      soak), or day 5 (after sprouting, before prepackaging 10 ppm chlorine rinse)--or
      control (no inoculum), and the ability of the inoculum to survive and grow was
      evaluated. Total bacterial numbers on uninoculated seeds increased dramatically
      during the first 24-h the seeds were soaked, from 3.5 to ca. 8.0 log CFU/g, and
      remained at this level during refrigerated storage. When the seeds were
      inoculated with a cocktail of L. monocytogenes (log 5 CFU/10 ml) on day 0 or 1,
      the population of the pathogen increased dramatically, to within 1 to 2 logs of
      the total, and remained high during refrigerated storage. When sprouted seeds
      were inoculated with L. monocytogenes later in the process (day 5), the inoculum
      survived but did not grow more than ca. 1 log CFU/g, regardless of whether the
      inoculation level in each jar was low (10(3)) or high (10(5)). Irradiation of
      sprouts with beta radiation at 3.3 or 5.3 kGy, but not 1.5 kGy, was effective at
      eliminating L. monocytogenes from inoculated sprouts (6 log CFU/g) without
      causing noticeable changes in appearance or odor. In summary, L. monocytogenes
      can grow on sprouts during production, can survive on refrigerated sprouts, and
      may be eliminated on sprouts with beta radiation.

PMID- 12182478
TI  - Influence of pH and temperature on the growth of and toxin production by
      neurotoxigenic strains of Clostridium butyricum type E.
AB  - Strains of Clostridium butyricum that produce botulinal toxin type E have been
      implicated in outbreaks of foodborne botulism in China, India, and Italy, yet the
      conditions that are favorable for the growth and toxinogenesis of these strains
      remain to be established. We attempted to determine the temperatures and pH
      levels that are most conducive to the growth of and toxin production by the six
      strains of neurotoxigenic C. butyricum that have been implicated in outbreaks of
      infective and foodborne botulism in Italy. The strains were cultured for 180 days
      on Trypticase-peptone-glucose-yeast extract broth at various pHs (4.6, 4.8, 5.0,
      5.2, 5.4, 5.6, and 5.8) at 30 degrees C and at various temperatures (10, 12, and
      15 degrees C) at pH 7.0. Growth was determined by checking for turbidity; toxin
      production was determined by the mouse bioassay. We also inoculated two foods:
      mascarpone cheese incubated at 25 and 15 degrees C and pesto sauce incubated at
      25 degrees C. The lowest pH at which growth and toxin production occurred was 4.8
      at 43 and 44 days of incubation, respectively. The lowest temperature at which
      growth and toxin production occurred was 12 degrees C, with growth and toxin
      production first being observed after 15 days. For both foods, toxin production
      was observed after 5 days at 25 degrees C. Since the strains did not show
      particularly psychrotrophic behavior, 4 degrees C can be considered a
      sufficiently low temperature for the inhibition of growth. However, the
      observation of toxin production in foods at room temperature and at abused
      refrigeration temperatures demands that these strains be considered a new risk
      for the food industry.

PMID- 12182479
TI  - Heat resistance of juice spoilage microorganisms.
AB  - The heat resistance of various yeasts (Saccharomyces cerevisiae, Rhodotorula
      mucilaginosa, Torulaspora delbrueckii, and Zygosaccharomyces rouxii), molds
      (Penicillium citrinum, Penicillium roquefortii, and Aspergillus niger), and
      lactic acid bacteria (Lactobacillus fermentum and Lactobacillus plantarum)
      obtained from spoiled acid or acidified food products was determined in 0.1 M
      citrate buffer at pH values of 3.0, 3.5, and 4.0. S. cerevisiae was the most heat
      resistant of the microorganisms in citrate buffer, and its heat resistance was
      further evaluated in apple, grapefruit, calcium-fortified apple, and tomato
      juices as well as in a juice base with high fructose corn syrup. Decimal
      reduction times (D-values) and changes in temperature required to change the D
      value (z-values) for S. cerevisiae were higher in the juices than in citrate
      buffer at all pH values tested. The D57 degrees C(135 degrees F)-values varied
      from 9.4 min in the juice product with pH 2.8 to 32 min in a calcium-added apple
      juice with pH 3.9. The S. cerevisiae strain used in this study can be used in
      thermal-death-time experiments in acidic products to calculate process conditions
      and in challenge tests to validate the calculated temperatures and hold times
      during processing.

PMID- 12182480
TI  - Effectiveness of electrolyzed water as a sanitizer for treating different
      surfaces.
AB  - The effectiveness of electrolyzed (EO) water at killing Enterobacter aerogenes
      and Staphylococcus aureus in pure culture was evaluated. One milliliter
      (approximately 10(9) CFU/ml) of each bacterium was subjected to 9 ml of EO water
      or control water (EO water containing 10% neutralizing buffer) at room
      temperature for 30 s. Inactivation (reduction of > 9 log10 CFU/ ml) of both
      pathogens occurred within 30 s after exposure to EO water containing
      approximately 25 or 50 mg of residual chlorine per liter. The effectiveness of EO
      water in reducing E. aerogenes and S. aureus on different surfaces (glass,
      stainless steel, glazed ceramic tile, unglazed ceramic tile, and vitreous china)
      was also evaluated. After immersion of the tested surfaces in EO water for 5 min
      without agitation, populations of E. aerogenes and S. aureus were reduced by 2.2
      to 2.4 log10 CFU/ cm2 and by 1.7 to 1.9 log10 CFU/cm2, respectively, whereas
      washing with control water resulted in a reduction of only 0.1 to 0.3 log10
      CFU/cm2. The washing of tested surfaces in EO water with agitation (50 rpm)
      reduced populations of viable cells on the tested surfaces to < 1 CFU/cm2. For
      the control water treatment with agitation, the surviving numbers of both strains
      on the tested surfaces were approximately 3 log10 CFU/cm2. No viable cells of
      either strain were observed in the EO water after treatment, regardless of
      agitation. However, large populations of both pathogens were recovered from
      control wash solution after treatment.

PMID- 12182481
TI  - Evaluation of the spiral plating system for the routine assessment of indicator
      microorganisms in raw ewe's milk.
AB  - The numbers of members of different microbial groups in bulk raw ewe's milk used
      for cheesemaking (46 samples, taken on receipt at the dairy over 1 year) were
      assayed by the spiral plating system to determine the effectiveness of this
      method compared with that of widely accepted conventional methods in providing
      counts. The results indicated that for ewe's milk, the suitability of the spiral
      plating system depends to a great extent on the microbial group studied. Although
      "spiral" counts of mesophiles, psychrotrophs, coliforms, and Enterobacteriaceae
      could be considered equivalent to those obtained by conventional techniques (r >
      or = 0.90; variance between replicate platings approximately 0.005), the
      automated method was found not to be suitable for the assessment of other groups
      of indicator bacteria (thermodurics and enterococci). Counts of lactic acid
      bacteria and yeasts and molds were affected significantly (P < 0.05) by the
      plating method, although other statistical parameters were more favorable (r =
      0.88 and r = 0.82, respectively; 95% confidence limits within 0.5 log units).
      Finally, counts of staphylococci, particularly on Baird-Parker medium, showed
      less variation and higher reproducibility with the spiral method. Nevertheless,
      for the routine microbiological analysis of ewe's milk, the spiral plating
      system, with its time-, effort-, and material-saving advantages, is preferred
      over the conventional method.

PMID- 12182482
TI  - Safety of consumer handling of fresh produce from the time of purchase to the
      plate: a comprehensive consumer survey.
AB  - A national mail survey focusing on consumer handling of fresh fruits and
      vegetables was conducted among 2,000 randomly selected households in the United
      States. The objective was to quantify consumer practices relating to the
      purchase, transport, storage, and preparation of fresh produce, with emphasis on
      practices that affect safety. Following an additional mailing procedure, a
      response rate of 33% was obtained. Six percent of the consumers responded that
      they seldom or never wash fresh produce, and more than 35% indicated that they do
      not wash their melons before preparation. Twenty-three percent of the respondents
      indicated placing their meat, poultry, and fish on a refrigerator shelf above
      other foods, and 9% do not place their produce at any specific location in the
      refrigerator. Almost half of the respondents indicated not always washing their
      hands before handling fresh produce. Ninety-seven percent of respondents reported
      that they always wash their food preparation surfaces after contact with meat
      products, yet 5% and 24% dry wipe or wash with water only, respectively. The
      results from this study suggest that women, lower-income households, people 65
      years and older, and non-college graduates practice safer food handling methods
      than men, higher-income households, people younger than 65 years, and college or
      postcollege graduates. The survey findings suggest that consumer education
      materials should emphasize safe handling practices from purchase through
      consumption. Educational outreach should target specific subpopulations, men,
      college graduates, higher-income households, and people younger than 65 years
      because of their higher frequency of unsafe handling and washing practices.

PMID- 12182483
TI  - Microbial quality of water supply to an urban community in Trinidad.
AB  - A microbiological study was conducted to determine the quality of the water
      supply to an urban community in San Fernando proper in south Trinidad using total
      coliforms and thermotolerant coliforms as indicators of water pollution. The
      membrane filter technique was used to detect total coliforms and thermotolerant
      coliforms on endo agar and MFc agar, respectively. The residual chlorine levels
      in water from the reservoir, from standpipes along the distribution line, and
      from households were determined with a commercial test kit. Of a total of 104
      drinking water samples obtained from households, 84 (80.8%), 56 (53.8%), and 70
      (67.3%) tested positive for total coliforms, thermotolerant coliforms, and
      Escherichia coli, respectively. The difference was statistically significant (P <
      0.05, chi2). Of the 81 water samples collected from the Water and Sewerage
      Authority (WASA) main supply to households, 38 (46.9%), 13 (16.0%), and 27
      (33.3%) were contaminated by total coliforms, thermotolerant coliforms, and E.
      coli, respectively, and the difference was statistically significant (P < 0.05,
      chi2). Eight (20.5%) of 39 water samples from standpipes along the distribution
      line tested positive for total coliforms, compared with 4 (10.3%) samples testing
      positive for thermotolerant coliforms. All five samples of treated water obtained
      from the reservoir tested negative for coliforms. There was a significant
      difference (P = 0.004) in the mean residual chlorine levels in water from the
      reservoir, water from standpipes, and water from households. Similarly, as the
      level of residual chlorine decreased, there was a statistically significant (P =
      0.004) increase in the prevalence of total coliforms in water from 0.0% (treated
      reservoir water) to 15.2% (standpipe) to 53.5% (household mains) to 80.0%
      (household drinking water). There was also a statistically significant difference
      (P < 0.001, chi2) in the prevalence of total coliforms in drinking water and in
      water from the WASA main supply to households. Of the 105 E. coli strains tested,
      7 (6.7%), 16 (15.2%), and 22 (21.0%) were mucoid, hemolytic, and non-sorbitol
      fermenters, respectively. It was concluded that the high degree of contamination
      of drinking water in households poses a health hazard to consumers.

PMID- 12182484
TI  - Development and application of an enzyme immunoassay based on a monoclonal
      antibody against gonyautoxin components of paralytic shellfish poisoning toxins.
AB  - With a gonyautoxin 2/3 (GTX2/3)-specific monoclonal antibody (designated GT-13A)
      and a saxitoxin-horseradish peroxidase conjugate (STX-HRP), a direct competitive
      enzyme immunoassay (GTX-EIA) was established and its sensitivity to various toxin
      components was investigated. The concentrations resulting in 50% inhibition of
      the binding of STX-HRP to the solid-phase GT-13A antibody for GTX2/3, decarbamoyl
      GTX2/3 (dc-GTX2/3), N-sulfocarbamoyl-GTX2/3 (C1/2), GTX1/4, STX, and neosaxitoxin
      (neoSTX) in GTX-EIA were found to be 0.28, 0.41, 0.52, 3.46, 4.06, and 89.37
      ng/ml, respectively. When the minimum detection limit was assumed to be at a
      toxin concentration causing 30% inhibition of the binding of STX-HRP to the solid
      phase GT-13A antibody, the detection limits for GTX2/3, dc-GTX2/3, C1/2, GTX1/4,
      STX, and neoSTX were found to be 0.15, 0.18, 0.19, 1.09, 1.50, and 22.93 ng/ml,
      respectively. These results indicate that all of the GTX components examined and
      STX are detectable at concentrations lower than the regulatory limit of 80
      microg/100 g of shellfish tissue, even when a minimum dilution factor of 100 is
      applied to tissue extracts with the extraction procedure of the Association of
      Official Analytical Chemists. Therefore, GTX-EIA is thought to be a useful
      qualitative screening method for GTX components and STX in the mass monitoring of
      toxin-contaminated shellfish.

PMID- 12182485
TI  - Apparent antifungal activity of several lactic acid bacteria against Penicillium
      discolor is due to acetic acid in the medium.
AB  - Fifty-six dairy bacteria belonging to the genera Lactococcus, Lactobacillus,
      Pediococcus, Propionibacterium, Streptococcus, Enterococcus, Leuconostoc, and
      Brevibacterium were screened for antifungal activity against four species of
      fungi relevant to the cheese industry (Penicillium discolor, Penicillium commune,
      Penicillium roqueforti, and Aspergillus vesicolor). Most of the active strains
      belonged to the genus Lactobacillus, whereas Penicillium discolor was found to be
      the most sensitive of the four fungi investigated. Further studies on P. discolor
      showed antifungal activity only below pH 5. This effect of pH suggests that
      organic acids present in the culture could be involved in the detected activity.
      Determination of acid composition revealed lactic acid production for active
      dairy strains and the presence of acetic acid in active as well as inactive
      strains. It was demonstrated that the undissociated acetic acid originates from
      the bacterial growth medium. The synergistic effect of the acetic acid present
      and the lactic acid produced was likely the main factor responsible for the
      antifungal properties of the selected bacteria. These results could explain some
      discrepancies in reports of the antifungal properties of lactic acid bacteria,
      since the role of acetic acid has not been considered in previous studies.

PMID- 12182486
TI  - Citrinin production and stability in cheese.
AB  - Citrinin is a nephrotoxic fungal metabolite that has been demonstrated to be
      mutagenic in hepatocytes. It can be produced by several fungal species that
      belong mainly to the genus Penicillium and has been isolated from many feeds and
      human foods. Cheese is a very sensitive product because it can be naturally
      contaminated by citrinin-producing molds. The purpose of this study was to
      determine whether citrinin can be produced in cheeses and whether it is stable in
      these products. Both toxigenic strains of Penicillium citrinum and Penicillium
      expansum used were able to produce citrinin in cheese at 20 degrees C, but not at
      4 degrees C. Up to 600 mg of citrinin per kg of cheese was obtained after 10 days
      of incubation. Interestingly, fresh goat cheese appeared to be a more favorable
      substrate for toxigenesis than did yeast extract-sucrose medium. Although
      contamination was mainly superficial, 33% of the toxin remained in cheese after
      trimming. Moreover, citrinin appeared to be very stable in some of the tested
      cheeses (goat cheese, Saint Marcellin, Soignon). For all cheeses tested, more
      than 50% of the initial content of citrinin was still present after 8 days of
      storage. Taken together, these results suggest that the contamination of cheeses
      by wild strains of Penicillium must be avoided.

PMID- 12182487
TI  - Prevalence of Shiga toxin-producing Escherichia coli in ground beef and cattle
      feces from King County, Washington.
AB  - Shiga toxin-producing Escherichia coli (STEC) is increasingly recognized as a
      common cause of diarrhea. STEC infection is a major public health threat because
      of its ability to cause serious and potentially life-threatening illnesses. The
      main reservoirs of STEC are believed to be the intestinal tracts of animals.
      Several studies have investigated the prevalence of STEC in various food items.
      The objective of this study was to determine the prevalence of STEC in the
      Seattle ground beef supply. In addition, the relative amount of STEC
      contamination between stores was compared, and possible differences between types
      of ground beef based on fat content (9, 16, and 23%) were investigated. A survey
      of Stx-I and/or Stx-II genes in fecal samples from cattle at a local
      slaughterhouse was also conducted. Of 296 ground beef samples tested from area
      retail grocery stores, 16.8% were positive for the presence of the toxin genes.
      Our data showed that there was no statistically significant difference (P > 0.05)
      in the prevalence of STEC between the ground beef samples of different fat
      contents and between grocery store chains. Of the 103 cattle fecal samples
      tested, 19 (18.4%) were found positive for the presence of Stx-I and/or Stx-II
      genes. The presence of a rather high percentage of STEC in the food supply in the
      absence of large number of cases suggests that not all STEC lineages are
      pathogenic for humans.

PMID- 12182488
TI  - Prevalence of thermophilic Campylobacter spp. in ready-to-eat foods and raw
      poultry in Northern Ireland.
AB  - Although there have been numerous studies investigating the prevalence of
      campylobacters in animals and raw meats, there are limited data on the
      persistence of these organisms in ready-to-eat (RTE) foodstuffs. Although poultry
      is now well established as a major reservoir of thermophilic campylobacters, it
      is widely assumed that hazard analysis critical control point (HACCP) controls in
      commercial and industrial settings are effective in eliminating this hazard
      through thorough cooking of RTE products. Therefore, it was the primary aim of
      this study to investigate the effectiveness of HACCP controls in eliminating
      campylobacters in such cooked RTE foods by attempting to isolate viable organisms
      from product. Concurrently, the results of this study demonstrate that local
      poultry is highly contaminated with campylobacters. Commercially available RTE
      foodstuffs (n = 2,030) consisting of 1,061 poultry-related cooked products and
      969 other products were analyzed and were not found to contain thermophilic
      Campylobacter spp. In addition, 107 raw chickens (63 fresh birds and 44 frozen
      birds) were sampled, and 94% of the fresh birds and 77% of the frozen birds
      examined were demonstrated to be contaminated with campylobacters, with
      Campylobacter jejuni, Campylobacter coli, and Campylobacter lari accounting for
      69, 30, and 1% of the contaminating organisms, respectively. In general,
      commercially available RTE foodstuffs, including cooked poultry, are not commonly
      contaminated with campylobacters and thus do not appear to represent a
      significant cause of clinical infection of Campylobacter spp. in Northern
      Ireland. However, raw poultry produce, including fresh and frozen chicken,
      frequently tested positive for campylobacters. Implementation of HACCP systems by
      food processors will help to minimize and/or eliminate the risk posed by this
      organism to the consumer.

PMID- 12182489
TI  - Rapid enumeration of Listeria monocytogenes in artificially contaminated cabbage
      using real-time polymerase chain reaction.
AB  - A quantitative real-time polymerase chain reaction (PCR) detection method
      specific for Listeria monocytogenes was developed, and studies involving pure
      culture showed that the response of the assay was linear over 7 log10 (log)
      cycles. The method was then applied to the detection of L. monocytogenes
      artificially inoculated onto cabbage, a vegetable chosen because it is a major
      component of coleslaw, which has been associated with an outbreak of listeriosis.
      After being allowed to attach to the food, cells were washed from the cabbage
      leaf surface and recovered by centrifugation. The DNA was purified by an organic
      solvent extraction technique and analyzed by real-time PCR. In this matrix, the
      method again produced a linear response over 7 log cycles from 1.4 x 10(2) to 1.4
      x 10(9) CFU of L. monocytogenes in 25 g of cabbage, and analysis of the
      reproducibility of the system showed that log differences in L. monocytogenes
      numbers added to cabbage could be reliably distinguished. The system allowed
      quantitative results to be obtained within 8 h and was relatively inexpensive,
      showing good potential for routine analytical use.

PMID- 12182490
TI  - Comparison of growth kinetics for healthy and heat-injured Listeria monocytogenes
      in eight enrichment broths.
AB  - Detection of Listeria in food products is often limited by performance of
      enrichment media used to support growth of Listeria to detectable levels. In this
      study, growth curves were generated using healthy and heat-injured Listeria
      monocytogenes strain F5069 in three nonselective and five selective enrichment
      broths. Nonselective enrichment media included the current Food and Drug
      Administration Bacteriological Analytical Manual Listeria enrichment broth base
      (BAM), Listeria repair broth (LRB), and Trypticase soy broth. Selective
      enrichment media included BAM with selective agents and LRB with selective
      agents, BCM L. monocytogenes preenrichment broth, Fraser broth, and UVM-modified
      Listeria enrichment broth. The Gompertz equation was used to model the growth of
      L. monocytogenes. Gompertz parameters were used to calculate exponential growth
      rate, lag-phase duration (LPD), generation time, maximum population density
      (MPD), and time required for repair of injured cells. Statistical differences (P
      < 0.05) in broth performance were noted for LPD and MPD when healthy and injured
      cells were inoculated into the broths. With the exception of Fraser broth, there
      were no significant differences in the time required for the repair of injured
      cells. Results indicate that the distinction between selective and nonselective
      broths in their ability to grow healthy Listeria and to repair sublethally
      injured cells is not solely an elementary issue of presence or absence of
      selective agents.

PMID- 12182491
TI  - Occurrence of aflatoxins and ochratoxin A in Indian poultry feeds.
AB  - From 1998 to 2001, 216 ingredients intended for incorporation into chicken feed,
      which included groundnut cake, maize, millets, rice bran, sorghum, soybean,
      sunflower, and mixed feeds, were assayed for aflatoxins and ochratoxin A
      contamination using an indirect competitive enzyme-linked immunosorbent assay.
      Thirty-eight percent of the samples were contaminated with aflatoxins and 6% with
      ochratoxin A. The incidence scores of aflatoxin contamination in excess of 10
      microg/kg were 41 of 95 for maize, 18 of 30 for mixed feeds, 10 of 37 for
      groundnut, 6 of 29 for sorghum, 5 of 10 for sunflower, 3 of 14 for rice bran, and
      1 of 8 for millet. Ochratoxin A contamination, in excess of 10 microg/kg, was
      found in 9 of 29 sorghum samples, 1 of 27 groundnut samples, 1 of 14 rice bran
      samples, 1 of 10 sunflower samples, and 2 of 8 millet samples. Ochratoxin A was
      not found in maize and mixed feeds. None of the three soybean samples contained
      ochratoxin A. This is the first report, to our knowledge, of co-occurrence of
      aflatoxins and ochratoxin A in Indian poultry feeds. The results confirm the
      importance of analysis of ingredients before incorporating them into mixed feeds.

PMID- 12182492
TI  - Tetrodotoxin in gastropods (snails) implicated in food poisoning in Northern
      Taiwan.
AB  - The toxin in the gastropods (snails) Zeuxis sufflatus and Niotha clathrata
      implicated in a food poisoning incident in northern Taiwan in April 2001 was
      studied. The symptoms exhibited by four victims were general paresthesia,
      paralysis of the phalanges and the extremities, paralysis, coma, vomiting, and
      aphasia. The remaining gastropods were assayed for toxicity in the form of
      tetrodotoxin (TTX). The ranges of specimen toxicity were 345 to 1,640 mouse units
      (MU) for Z sufflatus and 190 to 643 MU for N. clathrata. The toxicities of the
      digestive gland and for other parts of the gastropod were 1,120 +/- 477 MU and
      497 +/- 238 MU, respectively, for Z sufflatus and 683 +/- 113 MU and 289 +/- 169
      MU, respectively, for N. clathrata. The toxin from the methanolic extract of the
      gastropods was partially purified by ultrafiltration and Bio-Gel P-2 column
      chromatography. Cellulose acetate membrane electrophoresis, thin-layer
      chromatography, high-performance liquid chromatography, and gas chromatography
      mass spectrometry analyses demonstrated that the toxin consisted of TTX. It was
      concluded that the causative agent of the food poisoning in question was TTX.

PMID- 12182493
TI  - Direct detection of Cryptosporidium parvum oocysts by immunomagnetic separation
      polymerase chain reaction in raw milk.
AB  - Cryptosporidium parvum is an emerging protozoan parasite responsible for several
      serious outbreaks of cryptosporidiosis, an enteric infection characterized by
      severe intestinal distress. This parasite can be transmitted through contaminated
      water and raw food in the oocyst form, which is resistant to many environmental
      stresses and food processes. C. parvum is also commonly found on dairy farms and
      could be transmitted to humans through contaminated raw milk and dairy products.
      Thus, an immunomagnetic separation-polymerase chain reaction assay for direct
      detection of C. parvum oocysts in milk was developed. The procedure was able to
      detect < 10 C. parvum oocysts. Thus, it could be used for monitoring milk
      samples.

PMID- 12182494
TI  - Circadian phase and period responses to light stimuli in two nocturnal rodents.
AB  - We report period response curves (tauRC) for two nocturnal Murid species from
      India, Mus booduga and Mus platythrix. We further discuss the method of phase
      shift estimation in the presence of tau-changes, because such changes pose a
      serious methodological problem in the estimation of phase shifts. Although the
      tauRC indicates that most of the phase shifts are associated with small changes
      in tau, the period changes across all the phases showed a significant positive
      correlation with the phase shifts. We conclude that tauRCs are a reality even in
      nocturnal mammals, although their amplitude is less than what is usually found in
      diurnal mammals, and requires a larger data set to be distinguished from noise.

PMID- 12182495
TI  - Three days of novel wheel access diminishes light-induced phase delays in vivo
      with no effect on per1 induction by light.
AB  - The mammalian circadian clock, located in the hypothalamic suprachiasmatic
      nuclei, synchronizes endogenous behavioral and physiological rhythms to a 24 h
      period through responses to two types of stimuli: photic (light) and nonphotic
      (behaviorally induced arousal and/or increases in activity). Photic stimuli can
      block nonphotic effects and vice versa, although the mechanisms and levels of
      interactions between these two stimuli types are unknown. Here, we investigated
      whether 3 d of access to a novel running wheel alters the phase shift to light in
      vivo, and whether this effect could be seen on induction by light of the
      circadian gene per1. Through measurement of running wheel activity of golden
      hamsters, access to a new wheel for 3 d was shown to diminish photic phase delays
      with no effect on phase advances. As seen using in situ hybridization, however,
      there was no effect on levels of light-induced per1 mRNA. This study indicates a
      possible role for this paradigm as a model of interactions between photic and
      nonphotic stimuli.

PMID- 12182496
TI  - Circadian rhythm in plasma aldosterone concentration and its seasonal modulation
      in the camel (Camelus dromedarius) living in the Algerian Sahara desert.
AB  - Five male camels dwelling in the Algerian Sahara were studied for circadian
      rhythmicity in plasma aldosterone concentration and its seasonal modulation.
      Blood was sampled at a frequency of 1 h or less for a span of 27 h during each
      season of the year. The mean plasma aldosterone concentration exhibited a
      significant circadian rhythmicity in every season of the year. Plasma aldosterone
      concentration was lowest in the morning, increased in the afternoon, and
      generally highest in the late evening. The peak of the circadian rhythm exhibited
      seasonal variation; it occurred at 20:04h in October, 16:41h in December, 20:40h
      in March, and 24:16h in June. The rhythm's 24h mean also exhibited seasonal
      variability, being significantly higher in March and June compared to October.

PMID- 12182497
TI  - Sleep logs of young adults with self-selected sleep times predict the dim light
      melatonin onset.
AB  - The purpose of this study was to determine whether a sleep log parameter could be
      used to estimate the circadian phase of normal, healthy, young adults who sleep
      at their normal times, and thus naturally have day-to-day variability in their
      times of sleep. Thus, we did not impose any restrictions on the sleep schedules
      of our subjects (n = 26). For 14 d, they completed daily sleep logs that were
      verified with wrist activity monitors. On day 14, salivary melatonin was sampled
      every 30 min in dim light from 19:00 to 07:30 h to determine the dim light
      melatonin onset (DLMO). Daily sleep parameters (onset, midpoint, and wake) were
      taken from sleep logs and averaged over the last 5, 7, and 14 d before
      determination of the DLMO. The mean DLMO was 22:48 +/- 01:30 h. Sleep onset and
      wake time averaged over the last 5 d were 01:44 +/- 01:41 and 08:44 +/- 01:26 h,
      respectively. The DLMO was significantly correlated with sleep onset, midpoint,
      and wake time, but was most strongly correlated with the mean midpoint of sleep
      from the last 5 d (r = 0.89). The DLMO predicted using the mean midpoint of sleep
      from the last 5 d was within 1 h of the DLMO determined from salivary melatonin
      for 92% of the subjects; in no case did the difference exceed 1.5 h. The
      correlation between the DLMO and the score on the morningness-eveningness
      questionnaire was significant but comparatively weak (r = -0.48). We conclude
      that the circadian phase of normal, healthy day-active young adults can be
      accurately predicted using sleep times recorded on sleep logs (and verified by
      actigraphy), even when the sleep schedules are irregular.

PMID- 12182498
TI  - Gender differences in morningness-eveningness preference.
AB  - Morningness-eveningness preference (morning-, intermediate-, evening-type) or
      circadian typology is the individual difference that most clearly explains the
      variations in the rhythmic expression of biological or behavioral patterns. The
      aim of this study was to analyze gender difference in morningness-eveningness
      preference using the Horne and Ostberg questionnaire in the largest university
      student population selected so far (N = 2135), with an age range 18-30 yr.
      Morningness-eveningness questionnaire (MEQ) score distribution closely correlated
      to the normal curve (range 17-78, mean = 48.25; SD = 10.11), with 338 (15.84%)
      morning-types, 1273 (59.62%) intermediate-types, and 524 (24.54%) evening-types.
      The men and women differed significantly in their mean scores (p < 0.0001) and
      distribution per circadian typology (p < 0.00001), with the men presenting a more
      pronounced eveningness preference. Three factors were identified by factor
      analysis: time of greatest efficiency (I), sleep time/sleep phase (II), awakening
      time/sleep inertia (III). The MEQ items sensitive to gender differences were
      essentially those included in factor I and factor II. The results are discussed
      in relation to recent models of circadian regulation of the sleep-wake cycle.

PMID- 12182499
TI  - Regulation of the 24h body temperature rhythm of women in luteal phase: role of
      gonadal steroids and prostaglandins.
AB  - An investigation into whether the rise in the 24h body temperature rhythm
      observed in the luteal menstrual phase is antagonized by the administration of
      prostaglandin synthesis inhibitors has been made. Intravaginal body temperature
      was monitored continuously for 24h, once in the follicular and twice in the
      luteal phase. In the luteal phase, women were studied both without and with the
      simultaneous administration of a prostaglandin synthesis inhibitor (lysine
      acetylsalicylate; 1.8 g every 6 h orally). The progesterone/estradiol ratio
      (measured at 17:00h each day) was related to mesor (r = 0.825; P < 0.001),
      acrophase (r = 0.682; P < 0.02), and amplitude (r = -0.731; P < 0.001) of the 24h
      body temperature rhythm. Luteal phase elevation of the progesterone/estradiol
      ratio was associated with a 0.32 +/- 0.07 degrees C increase in mesor (P < 0.01),
      a 0.11 +/- 0.02 degrees C decrease in amplitude (P < 0.001), and a 34.8 +/- 11.6
      min delay in acrophase (P < 0.03) of the 24h body temperature rhythm.
      Prostaglandin synthesis inhibitors did not counteract these modifications. The
      present data shows that the modifications of the circadian parameters of the 24h
      body temperature rhythm observed during the luteal phase of the menstrual cycle
      are strictly related to modifications of the progesterone/estradiol ratio, and
      presumably independent of prostaglandin synthesis.

PMID- 12182500
TI  - The diurnal rhythm in isometric muscular performance differs with eumenorrheic
      menstrual cycle phase.
AB  - The aim of this study was to examine the effect of the interaction of circamensal
      and diurnal rhythms in temperature upon the production of maximal voluntary
      muscle force. Ten eumenorrheic females (mean age: 24 +/- 3 yr mean body mass:
      58.4 +/- 6.9 kg) participated in the experiment at both 06:00 and 18:00h at the
      mid-point of both the follicular and luteal phases of the menstrual cycle.
      Subjects performed tasks of maximal isometric lifting strength (MILS) at knee
      height, and endurance time (t) for lifting 45% of MILS, upon an isometric lift
      dynamometer. Body temperature was elevated at 18:00h and in the luteal phase by
      0.52 +/- 0.4 and 0.26 +/- 0.35 degrees C, respectively. The amplitude of the
      diurnal variation in temperature was blunted by 0.3 degrees C within the luteal
      phase. Maximal isometric performance was elevated by 8% at 18:00h in the luteal
      phase of the cycle (p < 0.05 interaction for MILS) but unaffected by time of day
      in the follicular phase. Endurance time was unaffected by time or phase (p >
      0.05). It should be noted that the classic diurnal rhythm in maximal voluntary
      isometric muscle force may not be evident in all phases of the female menstrual
      cycle.

PMID- 12182501
TI  - Jet lag in athletes after eastward and westward time-zone transition.
AB  - In healthy male top athletes several functions were measured after either a
      westbound flight over six time-zones (WEST: Frankfurt-Atlanta; n = 13) or an
      eastbound flight over eight time-zones (EAST: Munich-Osaka; n = 6). Under either
      condition the athletes performed two standardized exercise training units in the
      morning and in the afternoon within 24 h, investigations were done as controls in
      Germany and on day 1, 4, 6, and 11, after arrival. The primary aim of the study
      was to evaluate the effect of time-zone transitions on the 24h profiles of blood
      pressure (BP) and heart rate (HR) using an ambulatory BP device (SpaceLabs
      90207), for up to 11 d after arrival at the destination. As additional
      parameters, we studied jet-lag symptoms, training performance, and training
      coordination by using visual analog scales. Finally, oral temperature and grip
      strength were measured, and saliva samples were analyzed for cortisol and
      melatonin. The study showed that all functions were disturbed on the first day
      after arrival at the destination, jet-lag symptoms remained until day 5-6 after
      WEST and day 7 after EAST, training performance was worst within the first 4 d
      after WEST. In accordance with earlier reports, cortisol, melatonin, body
      temperature, and grip strength were affected in their 24h profiles and
      additionally modified by the training units. Surprisingly, BP and HR were not
      only affected on the first day but also the time-zone transition led to an
      increase in BP after WEST and a decrease in BP after EAST. However, the training
      units seemed to influence the BP profile more than the time-zone transitions. HR
      rhythm was affected by both time-zone transitions and exercise. It is concluded
      that not only jet-lag symptoms but also alterations in physiological functions
      should be considered to occur in highly competitive athletes due to time-zone
      transition and, therefore, an appropriate time of reentrainment is recommended.

PMID- 12182502
TI  - Circadian pattern of blood pressure, heart rate, and double product in liver
      glycogen storage disease.
AB  - The objective of this study was to determine systolic, diastolic, and mean
      arterial blood pressure (SBP, DBP, and MAP), heart rate (HR), double-product (DP:
      SBP x HR), and activity levels and their 24h pattern in liver glycogen storage
      disease (LGSD) patients. A case series of 12 (11 pediatric and one adult)
      diurnally active LGSD (seven type I, three type III, and two type IX) subjects
      were simultaneously assessed by 24h ambulatory blood pressure monitoring and
      wrist actigraphy. Nine subjects were judged to be hypertensive based on the
      criterion of an elevated 24h mean SBP and/or DBP being elevated beyond reference
      standards or the SBP and/or DBP load (percentage of time BP exceeds normal
      values) being greater than 25%. Two of the three other subjects, not viewed as
      hypertensive based on their 24h average SBP or DBP, exhibited daytime or
      nighttime SBP and/or DBP load hypertension. Each study variables displayed
      statistically significant (p < 0.001) group circadian rhythmicity. The SBP, DBP,
      and MAP displayed comparable 24h patterns of appreciable amplitude (total peak
      trough variation equal to 17.7, 23.6, and 19.6%, respectively, of the 24h mean)
      with highest values (orthophase) occurring approximately 11 h after the
      commencement of daytime activity. The sleep-time trough (bathyphase) occurred
      approximately 4.5 h before morning awakening. The statistically significant (p <
      0.006) circadian rhythms of HR (amplitude equal to 33.2% of the 24h mean) and DP
      (amplitude equal to 49.4% of the 24h mean) peaked earlier, approximately 7.4 h
      into the daytime activity span. The sleep-time trough occurred approximately 3 h
      before morning awakening. The 24h pattern in the cardiovascular variables was
      correlated with the 24h pattern of activity, with r ranging from 0.50 for DBP to
      0.39 for HR.

PMID- 12182503
TI  - Morning preference in onset of symptomatic third-degree atrioventricular heart
      block.
AB  - The aim of this study was to examine 24h patterning in the symptoms indicative of
      third-degree atrio-ventricular (AV) heart block. We found a total of 227 cases
      (126 men and 101 women) of third-degree AV block that had been diagnosed by the
      Emergency Medical Department of the St. Anna Hospital in Ferrara, Italy between
      1990 and 2001. Determination of the hour of onset of symptomatic third-degree AV
      block, however, was possible and listed in the records of only 161 or 70.9% of
      the cases (92 men and 69 women). The onset time of every event was categorized
      into one of four 6h spans of the 24h: night (00:00-05:59h), morning (06:00
      11:59h), afternoon (12:00-17:59h), and evening (18:00-23:59h). The onset of the
      symptoms of third-degree AV block in the sample of 161 cases was significantly
      greater in the morning between 06:00 and 11:59h than any other 6h span of the day
      and night (chi2-test; p < 0.001). The same phenomenon was substantiated in the
      subgroup of the 92 males (chi2; p < 0.0001), although it could not be detected
      for the smaller subgroup of 69 women. The 24h pattern, with morning preference,
      in the onset of symptomatic third-degree AV block is similar to the one in sudden
      cardiac death and cardiogenic cardiac arrest. The etiology of the 24h pattern in
      symptomatic AV block is unknown; it may be an expression of intrinsic biological
      rhythmicity within the heart tissue or its control system, and/or the timing of
      environmental triggers resulting in coronary ischemia.

PMID- 12182504
TI  - Ciclograma: a tool for detection of rhythmicities in sleep/wake cycles.
AB  - The Fourier spectral analysis of binary time series (or rectangular signals)
      causes methodological problems, due to the fact that it is based on sinusoidal
      functions. We propose a new tool for the detection of periodicities in binary
      time series, focusing on sleep/wake cycles. This methodology is based on a
      weighted histogram of cycle durations. In this paper, we compare our methodology
      with the Fourier spectral analysis on the basis of simulated and real binary data
      sets of various lengths. We also provide an approach to statistical validation of
      the periodicities determined with our methodology. Furthermore, we analyze the
      discriminating power of both methods in terms of standard deviation. Our results
      indicate that the Ciclograma is much more powerful than Fourier analysis when
      applied on this type of time series.

PMID- 12182505
TI  - Mood and behaviour problems associated with seasonal changes in Britain and
      Ireland.
AB  - BACKGROUND: Research from across the world has shown that rates of seasonal mood
      disturbances may vary according to such factors as geographical location, age and
      gender. Little is known of the nature of these problems within representative
      community samples in UK and Ireland. AIMS: In two studies we examined the extent
      to which winter disrupts mood and behaviour among random samples of British and
      Irish adults. METHODS: In the first study, 533 adults randomly chosen from
      electoral data from four towns spread across 50-58 degrees N completed the
      Seasonal Pattern Assessment Questionnaire (SPAQ). In the second study, 498 adults
      from two towns in Northern Ireland (54 degrees N) completed the SPAQ. RESULTS:
      Although the combined response rate across the two studies was low (20.5%), the
      prevalence rates were similar to several other western European sites. The rate
      of SAD and S-SAD averaged across the six centres as determined from strict SPAQ
      criteria, was 6.7% and 10.5% respectively. There was some variability in rates
      from town to town, with one Northern Irish town presenting rates more associated
      with areas at much lower latitudes, although most differences between towns were
      not significant. As in most other studies, females of reproductive age tended to
      supply the higher number of incidences. CONCLUSION: This report from community
      samples across six sites confirms earlier suggestions that rates of seasonal
      disturbance in mood and behaviour deserve serious consideration by mental health
      practitioners throughout the region.

PMID- 12182506
TI  - Family type and criminal behaviour of male offspring: the Northern Finland 1966
      Birth Cohort Study.
AB  - BACKGROUND: Unstable family environment during childhood is known to predispose
      to juvenile delinquency. AIMS: This study explored whether childhood family
      structure is associated with violent behaviour of adult offspring. METHODS: We
      used a large, unselected general population birth cohort (n = 5589 males) linked
      with the national crime registers (up to the age of 32 years). The Ministry of
      Justice provided information on registered offences for all subjects. A logistic
      regression analysis was performed to examine the association between family type
      and criminality (violent and non-violent crimes). RESULTS: We found that single
      parent family "at birth" (adj. OR 3.6, 95% CI 1.8-7.0) and "all time" (up to the
      age of 14 years) (adj. OR 5.2, 95% CI 2.5-10.6) were risk factors for violent
      offences of an adult offspring. Also parental death (adj. OR 2.2, 95% CI 1.3-3.6)
      and divorce (adj. OR 2.5, 95% CI 1.6-3.7) doubled the risk for violence. Non
      violent offences were associated only with parental death and, divorce.
      CONCLUSIONS: A single-parent family of origin is strongly associated with later
      violent criminality of male offspring. Further studies are needed to explore the
      psychosocial aspects of single-parent family environment which may promote the
      vulnerability to violent offending in adulthood.

PMID- 12182507
TI  - Psychiatric emergencies and the millennium: an international study.
AB  - BACKGROUND: The millennium posed an unknown challenge to mental health services
      worldwide. In anticipation, contingencies were implemented in preparation for the
      unexpected impact on psychiatric morbidity. RESULTS: This study evaluates the
      impact of the millennium on psychiatric emergency service utilization in the
      Northern and Southern hemispheres--the UK, Nigeria and Australia. Findings did
      not demonstrate a notable "millennium effect" on mental health services. A number
      of patients presented psychopathology incorporating millennium themes. A post
      Christmas and post-New Year increase in presentation was observed. CONCLUSION:
      There was no change in service needs.

PMID- 12182508
TI  - Effect of culture and environment on the phenomenology of delusions and
      hallucinations.
AB  - BACKGROUND: The present study was conducted to compare the influence of culture
      and immediate environment on the phenomenology of schizophrenic symptoms by
      examining the actual content of delusions and hallucinations in three groups of
      schizophrenic patients. METHOD: Pakistanis living in Britain (BP; N = 53),
      Pakistanis in Pakistan (PP; N = 98) and British White (BW; N = 50). The content
      of the patients' delusions and hallucinations was obtained from medical records
      and key-workers' reports from All-Saints Hospital, Birmingham and two psychiatric
      units in Lahore. All references to delusions and hallucinations were coded in
      accordance with the classification scheme developed for the Present State
      Examination (Wing et al., 1974). RESULTS: Comparisons indicated greater
      differences in phenomenology of delusions and hallucinations between the
      Pakistani pair (BP vs. PP) than between the British groups (BP vs. BW). The
      findings suggested a stronger influence of the immediate environment on the
      pathogenesis of delusions and hallucinations. CONCLUSIONS: The results are
      discussed with reference to the cultural and religious values of the ethnic
      groups.

PMID- 12182509
TI  - A randomised controlled trial of an educational intervention for depression among
      Asian women in primary care in the United Kingdom.
AB  - OBJECTIVE: To determine the effect of patient education on patient perspectives
      and outcome of depression in a sample of Asian women in primary care. DESIGN: A
      randomised, clinical trial of "patient education" versus "usual care". SETTING: A
      general practice in London, which has a high proportion of Asians. SUBJECTS:
      Seventy patients with psychiatric morbidity (a score of 3 or more on the General
      Health Questionnaire 12) were recruited for the trial. OUTCOME MEASURES:
      Patient's explanatory models of illness (the patient's perspective on depression;
      recognition of depression as illness and recommend a medical intervention for
      this condition) and psychiatric morbidity at follow-up after two months were the
      primary outcome measures. RESULTS: One hundred and fifty-five women of Asian
      decent were contacted. One hundred and forty-eight (95.5%) agreed to take part in
      the study. Seventy (47.3%) were classed as cases of common mental disorder using
      the General Health Questionnaire 12. Thirty-five were randomly allocated to
      receive education about the nature, causes, prevalence and treatment of
      depression, 35 did not receive such information. There were no statistical
      differences between the two groups on baseline characteristics. Sixty-six (94.3%)
      subjects were followed up at two months. An intention to treat analysis showed
      that there was no difference in explanatory model measures between the two groups
      at the end of the study. However, more patients who received education were no
      longer cases (a score of 2 or less on the GHQ) (15/35; 42.9%) compared to
      controls (7/35; 20%) (p < 0.05) as did those with lower GHQ scores at entry (p <
      0.03). Receipt of educational intervention (OR 3.4; 95% CI 1.01, 11.5) and lower
      GHQ scores at entry (OR 7.1; 95% CI 1.05, 30.2) remained significantly associated
      with recovery after adjusting for baseline variables using logistic regression.
      CONCLUSIONS: Patients with common mental disorders, especially those with milder
      forms of the condition, who received the educational material had a higher
      recovery rate than patients who do not receive such education. The mechanism for
      this improvement was unclear, not being reflected in patient's apparent
      understanding of depression nor explained by change in general practitioner's
      response. The results of this study need to be replicated.

PMID- 12182510
TI  - Abuse of carers by relatives with severe mental illness.
AB  - BACKGROUND: Relatives often experience considerable problems looking after a
      family member with severe mental illness. The problems arising from verbal and
      physical abuse are not well researched or acknowledged. AIMS: To examine the
      frequency with which family carers experienced verbal and physical abuse from
      relatives who were being looked after by a community mental health service and to
      identify the correlates and consequences of that abuse. METHOD: Interviews with
      all the clients of a community mental health service in suburban Melbourne who
      had regular contact with a family carer together with interviews with the carers.
      RESULTS: One hundred and one clients and their family carers were interviewed.
      Supporting a previous study of patients on an acute admission ward, the
      experiences of verbal and physical abuse were positively correlated. Higher rates
      of abuse were associated with poor relationships between patients and their
      families and a history of poly-drug misuse and previous criminal offences on the
      part of the patient. Relatives experiencing higher levels of abuse were more
      likely to have. symptoms of emotional distress and were rated as experiencing
      more burden. CONCLUSIONS: Verbal and physical abuse are not infrequent problems
      facing family members caring for a relative with severe mental illness. Some of
      the risk factors for such abuse can be identified. Care plans for family carers
      could usefully target risk reduction strategies to minimise the occurrence of
      abuse.

PMID- 12182511
TI  - Community rehabilitation service for patients with severe psychotic disorders:
      the Slovene experience.
AB  - BACKGROUND: Rehabilitation can be carried out at various sites. METHOD: Two
      groups of patients with severe mental disorders were compared: those included in
      community rehabilitation service and those only attending an outpatient clinic
      regarding their clinical status, social functioning, standard of living and
      quality of life. RESULTS: We found no significant global differences in group
      characteristics, social functioning and clinical status, but we did prove the
      lower social status of the group included in the rehabilitation service and their
      satisfaction with the services they use. CONCLUSIONS: The community
      rehabilitation services in Slovenia are coping with existential social needs of
      their users but this study failed to demonstrate their success in improving
      health or social functioning.

PMID- 12182512
TI  - Mental health care in primary and community settings: results from WHO's Project
      Atlas.

PMID- 12182513
TI  - Trauma and the Kanun: two responses to loss in Albania and Kosova.
AB  - Social anthropology has proposed that social institutions and psychological
      reactions may at times be alternative ways of dealing with similar situations;
      and that at a high level of generality, they may be conceived of as variants of
      similar (psycho-social) phenomena. Response to sudden bereavement in Albanian
      Kosova may follow two routes: the customary law arguing stoicism but retribution,
      and the psychological idiom of 'trauma' recently introduced by Western European
      aid agencies. Similarities and differences between what at first appear two quite
      distinct responses are outlined.

PMID- 12182514
TI  - Psychiatric units in Brazilian general hospitals: a growing philanthropic field.
AB  - BACKGROUND: Some countries, mainly in North America and Europe, have adopted
      psychiatric wards in the general hospital as an alternative to the classic
      psychiatric hospital. In Brazil there are 6,169 general hospitals, 1.3% of which
      with a psychiatric unit. This service strategy is scarcely developed in the
      country and comprises only 4% of all psychiatric admissions. There was no
      information on the facilities and functioning of the psychiatric units in general
      hospitals. OBJECTIVE: To determine the main characteristics of psychiatric units
      in Brazilian general hospitals and to assess the current trends in the services
      provided. METHOD: A mailing survey assessed all 94 Brazilian general hospitals
      which made psychiatric admissions. A two-page questionnaire was designed to
      determine the main characteristics of each institution and of the psychiatric
      unit. RESULTS: Seventy-nine (84%) questionnaires were returned. In contrast to
      the 1970s and 1980s, in the last decade the installation of psychiatric units has
      spread to smaller philanthropic institutions that are not linked to medical
      schools. A fifth of hospitals admit psychiatric patients to medical wards because
      there is no specialist psychiatric ward. They try to meet all the local emergency
      demands, usually alcohol-dependent patients who need short term admission. This
      could signal the beginning of a program through which mental health professionals
      may become an integral part of general health services. CONCLUSION: The
      inauguration of psychiatric wards in philanthropic hospitals, as well as the
      admission of psychiatric patients in their medical wards, is a phenomenon
      peculiar to this decade. The installation of psychiatric services in these and
      other general hospitals would overcome two of major difficulties encountered:
      prejudice and a lack of financial resources.

PMID- 12182515
TI  - Postpartum eclampsia.

PMID- 12182516
TI  - Preventing postpartum weight retention.

PMID- 12182517
TI  - Do children with acute asthma benefit more from anticholinergics and beta2
      agonists than from beta2 agonists alone?

PMID- 12182518
TI  - Environmental control of allergic diseases.
AB  - Allergic disease affects millions of persons in the United States. Environmental
      control measures are essential for persons who are sensitive to dust mite and cat
      allergens and may be important in persons who are sensitive to cockroaches and
      fungus. The bedroom is the most important room in which to implement
      environmental control measures, such as encasing mattresses and pillows in vinyl
      or semipermeable covers. Patients with asthma (especially persistent asthma)
      should be considered for allergy testing and more aggressive environmental
      control measures. Carpet in the bedroom or over concrete should be removed. For
      persons who are sensitive to pet allergens, permanent removal of the pet is
      recommended. Dust mite and fungus growth can be controlled by keeping the
      household humidity level at less than 50 percent. Removing sources of food and
      water and using insecticides will help control cockroach populations. Patients
      who are sensitive to mold and outdoor air pollution should consider limiting
      outdoor activities when these levels are high. Patients with asthma should avoid
      exposure to tobacco smoke. (Am Fam Physician 2002;66:429-30.)

PMID- 12182519
TI  - Information from your family doctor. Things that can cause asthma and allergies.

PMID- 12182520
TI  - Rosacea: a common, yet commonly overlooked, condition.
AB  - Rosacea is a common, but often overlooked, skin condition of uncertain etiology
      that can lead to significant facial disfigurement, ocular complications, and
      severe emotional distress. The progression of rosacea is variable; however,
      typical stages include: (1) facial flushing, (2) erythema and/or edema and ocular
      symptoms, (3) papules and pustules, and (4) rhinophyma. A history of exacerbation
      by sun exposure, stress, cold weather, hot beverages, alcohol consumption, or
      certain foods helps determine the diagnosis; the first line of treatment is
      avoidance of these triggering or exacerbating factors. Most patients respond well
      to long-term topical antibiotic treatment. Oral or topical retinoid therapy may
      also be effective. Laser treatment is an option for progressive telangiectasis or
      rhinophyma. Family physicians should be able to identify and effectively treat
      the majority of patients with rosacea. Consultation with subspecialists may be
      required for the management of rhinophyma, ocular complications, or severe
      disease. (Am Fam Physician 2002;66:442.)

PMID- 12182521
TI  - Information from your family doctor. Rosacea--what is it, and what can I do about
      it?

PMID- 12182522
TI  - Managing hypertension in athletes and physically active patients.
AB  - Athletes and other physically active patients should be screened for hypertension
      and given appropriate therapy if needed. Mild hypertension should be treated with
      non-pharmacologic measures for six months. If blood pressure control is adequate,
      lifestyle modifications are continued. If control is inadequate, low-dose therapy
      with an angiotensin-converting enzyme inhibitor or a calcium channel blocker may
      be started. A thiazide diuretic may be used as first-line treatment for
      hypertension in casually active patients; however, diuretic therapy is less
      desirable in high-intensity or endurance athletes because of the risk of
      hypovolemia or hypokalemia. If beta blockade is needed, a combined alpha-beta
      blocker may be the best choice. When the target blood pressure is achieved, long
      term follow-up care and management should be emphasized. If excellent control is
      maintained for six to 12 months, medication may be reduced or withdrawn in a
      small number of patients. If the target blood pressure is not achieved, the
      medication dosage may be adjusted, or a second medication, usually a diuretic,
      may be added. Physicians need to be aware of the effects of various medications
      on exercise tolerance and the rules for participation established by sports
      regulatory bodies (Am Fam Physician 2002;66:457-8).

PMID- 12182523
TI  - Information from your family doctor. High blood pressure and exercise.

PMID- 12182525
TI  - Information from your family doctor. What should I know about ACE inhibitors?

PMID- 12182526
TI  - Thromboembolism.

PMID- 12182524
TI  - Using ACE inhibitors appropriately.
AB  - When first introduced in 1981, angiotensin-converting enzyme (ACE) inhibitors
      were indicated only for treatment of refractory hypertension. Since then, they
      have been shown to reduce morbidity or mortality in congestive heart failure,
      myocardial infarction, diabetes mellitus, chronic renal insufficiency, and
      atherosclerotic cardiovascular disease. Pathologies underlying these conditions
      are, in part, attributable to the renin-angiotensin-aldosterone system.
      Angiotensin II contributes to endothelial dysfunction. altered renal
      hemodynamics, and vascular and cardiac hypertrophy. ACE inhibitors attenuate
      these effects. Clinical outcomes of ACE inhibition include decreases in
      myocardial infarction (fatal and nonfatal), reinfarction, angina, stroke, end
      stage renal disease, and morbidity and mortality associated with heart failure.
      ACE inhibitors are generally well tolerated and have few contraindications. (Am
      Fam Physician 2002;66:473.)

PMID- 12182527
TI  - Facial rash.

PMID- 12182528
TI  - AAP issues guidelines for selecting and using the most appropriate car safety
      seats. American Academy of Pediatrics.

PMID- 12182529
TI  - Prospective replication of the Violence Risk Appraisal Guide in predicting
      violent recidivism among forensic patients.
AB  - An exhaustive survey of a cohort of forensic patients provided an opportunity for
      a prospective replication of the predictive accuracy of the Violence Risk
      Appraisal Guide (VRAG). Data collected during the original survey also permitted
      a test of the predictive accuracy of clinical assessments of risk on the same
      cohort. The VRAG yielded a large effect size in predicting violent recidivism
      (ROC area = .80) over a constant 5-year follow-up and performed significantly
      better than averaged clinical opinions. The superiority of the VRAG was also
      observed at very short follow-up times and for very serious violence. Moreover,
      for 16 subsamples, observed rates of violent recidivism did not differ
      significantly from the expected rates. VRAG score was unrelated, and clinical
      judgments inversely related to violent recidivism in the small low-risk sample of
      female forensic patients. The authors conclude that, regardless of length of
      opportunity or severity of outcome, actuarial methods are more accurate than is
      clinical judgment.

PMID- 12182530
TI  - Children's conceptual knowledge of lying and its relation to their actual
      behaviors: implications for court competence examinations.
AB  - Child witnesses must undergo a competence examination in which they must show
      appropriate conceptual understanding of lying and truth-telling, and promise to
      tell the truth. Three experiments (Ns = 123, 103, 177) were conducted to address
      the assumptions underlying the court competence examination that (1) children who
      understand lying and its moral implications are less likely to lie and (2)
      discussing the conceptual issues concerning lying and having children promising
      to tell the truth promotes truth-telling. Both measures of lying and
      understanding of truth- and lie-telling were obtained from children between 3 and
      7 years of age. Most children demonstrated appropriate conceptual knowledge of
      lying and truth-telling and the obligation to tell the truth, but many of the
      same children lied to conceal their own transgression. Promising to tell the
      truth significantly reduced lying. Implications for legal systems are discussed.

PMID- 12182531
TI  - Reactions to mandatory sentences in relation to the ethnic identity and criminal
      history of the offender.
AB  - This study investigated the responses of 181 participants (87 men, 94 women),
      from Adelaide, South Australia, to scenarios describing mandatory sentences for
      perpetrators of a property offense committed in the Northern Territory,
      Australia. Four scenarios that were randomly distributed varied ethnic identity
      (White Australian, Aboriginal Australian) and criminal history (first-time
      offender, third-time offender). Participants completed attitude measures for both
      mandatory sentencing and capital punishment, a right-wing authoritarianism scale,
      and a scale concerned with sentencing goals (retribution, deterrence, protection
      of society, and rehabilitation). Results showed strong effects of attitude toward
      mandatory sentencing on scenario responses for variables such as perceived
      responsibility, deservingness, leniency, seriousness, anger and pleasure, and
      weaker effects of ethnic identity and criminal history. Participants were
      generally more sympathetic when the offender was an Aboriginal Australian.
      Results of a multiple regression analysis showed that attitude toward mandatory
      sentence was predicted by right-wing authoritarianism and by sentencing goals
      relating to deterrence and the protection of society.

PMID- 12182532
TI  - Validity of the mockwitness paradigm: testing the assumptions.
AB  - Mockwitness identifications are used to provide a quantitative measure of lineup
      fairness. Some theoretical and practical assumptions of this paradigm have not
      been studied in terms of mockwitnesses' decision processes and procedural
      variation (e.g., instructions, lineup presentation method), and the current
      experiment was conducted to empirically evaluate these assumptions. Four hundred
      and eighty mockwitnesses were given physical information about a culprit,
      received 1 of 4 variations of lineup instructions, and were asked to identify the
      culprit from either a fair or unfair sequential lineup containing 1 of 2 targets.
      Lineup bias estimates varied as a result of lineup fairness and the target
      presented. Mockwitnesses generally reported that the target's physical
      description was their main source of identifying information. Our findings
      support the use of mockwitness identifications as a useful technique for
      sequential lineup evaluation, but only for mockwitnesses who selected only 1
      lineup member. Recommendations for the use of this evaluation procedure are
      discussed.

PMID- 12182533
TI  - Examining the construct validity of the original and revised JBS: a cross
      validation of sample and method.
AB  - Factor analysis is a statistical technique that can provide an understanding of
      construct validity. Previous research examining the factor structure of the Juror
      Bias Scale (JBS) has uncovered problems in the scale's assessment of the
      constructs of probability of commission (PC) and reasonable doubt (RD). We here
      reevaluate the scale's constructs to better our understanding of the pretrial
      biases involved in the juror decision-making process. Importantly, previous
      findings have been limited to college student samples and trial material that has
      involved rape evidence. This study examines the construct validity of the JBS in
      a sample of 617 jury-eligible adults drawn from the community, and the predictive
      validity of the JBS is examined across 3 distinct trial scenarios. The results
      parallel earlier findings, indicating that although RD is a tenable and useful
      construct affecting juror decision-making, PC may be a less relevant pretrial
      bias. We therefore suggest that future research emphasize alternative constructs,
      such as confidence and cynicism in the criminal justice system.

PMID- 12182534
TI  - Assay of specific antibodies produced in organs of mice immunized with nerve
      growth factor.
AB  - Immunization of mice with nerve growth factor (NGF) leads to the production of
      antibodies, which can be assayed, from the serum. Currently, it is considered
      that the spleen of an immunized animal is predominantly involved in the
      production of antibodies. Therefore, spleen cells of the immunized animal are
      used to fuse with the respective species of myeloma cells to create in vitro
      immortalized antibodies secreting hybridomas. This investigation reports that
      besides spleen, other organs are involved in the production of antibodies. Adult
      Balb/c female mice were immunized with cobra venom derived NGF, 10 microg/mouse,
      three times, ten days apart. A set of immunized mice was sacrificed after each
      injection for organs. The serum and organ homogenates were assayed for antibodies
      specific to NGF. It was revealed that the liver and the ovaries showed the
      highest level of antibodies, higher than serum of the immunized mice. Spleen
      showed a higher level of antibodies than kidney, lung, and salivary glands. The
      homogenates of bone, brain, muscle, pancreas, and skin did not show detectable
      antibodies. This is a first-hand investigation reporting the involvement of
      organs other than spleen in the production of antibodies.

PMID- 12182535
TI  - A novel low molecular weight hemorrhagic toxin from Trimeresurus flavoviridis
      (Vorojima) venom.
AB  - A low molecular weight hemorrhagic toxin, LMHT, was isolated from the venom of
      Trimeresurus flavoviridis from Yorojima using Q-Sepharose column chromatography.
      The purified hemorrhagic toxin was homogeneous by disc polyacrylamide gel
      electrophoresis at pH 8.3, and Ouchterlony immunodiffusion. LMHT has a molecular
      weight of 16,500 and possesses hemorrhagic activity. It did not show casein,
      azocasein, azoalbumin, or TAME (tosyl-L-arginine methyl ester hydrochloride)
      hydrolytic activities. Hemorrhagic activity was inhibited by EDTA, TEP
      (tetraethylenepentamine), p-APMSF(p-amidinophenylmethanesulfonylfluoride HCl),
      and N-bromosuccinimide. The minimum hemorrhagic dose of this hemorrhagic toxin
      was 7.1 microg/mouse. LMHT induced hydrolysis of the Aa and Bbeta chains of
      bovine fibrinogen.

PMID- 12182536
TI  - Toxicity of tannins towards the free-living nematode Caenorhabditis elegans and
      the brine shrimp Artemia salina.
AB  - Toxicities of gallo- and condensed tannins towards the free-living nematode
      Caenorhabditis elegans is dependent on the tannins' molecular sizes. In the
      present paper we investigate the toxicity of ellagitannins to C elegans and the
      toxicity of ellagi-, gallo-, and condensed tannins to the brine shrimpArtemia
      salina. Ellagitannins 1 and 2 were isolated from Euphorbia supina and identified
      as tellimagrandin I and rugosin A methyl ester, respectively. An ellagitannin
      preparation from Cornus officinalis was chromatographically fractionated into
      ellagitannins A through H, having different molecular weights and specific
      rotations. Three of the ten ellagitannins, 2, G, and H produced significant
      toxicity towards C. elegans, showing the presence of an activity-structure
      relationship, as opposed to the results from tests of gallo- and condensed
      tannins. Ellagi-, gallo-, and condensed tannins also produced toxicity in A.
      salina.

PMID- 12182537
TI  - Comparison of phytotoxicity and mammalian cytotoxicity of nontrichothecene
      mycotoxins.
AB  - The phytotoxicity and mammalian cytotoxicity of four nontrichothecene mycotoxins
      (apicidin, sambutoxin, wortmannin, HC-toxin) were compared. Phytotoxicity was
      evaluated in terms of electrolyte leakage, growth inhibition, and reduction in
      chlorophyll content. Based on the parameters evaluated, the relative order of
      phytotoxicity to duckweed (Lemna pausicostata L.) was wortmannin > HC-toxin >
      apicidin >> sambutoxin. A 48-hr exposure to 10 microM wortmannin, HC-toxin or
      apicidin caused electrolyte leakage from duckweed. The IC50 values for growth
      inhibition and chlorophyll reduction for wortmannin, HC-toxin, and apicidin were
      0.2 and 2.6 microM, 15.4 and 12.6 microM, and 27.7 and 45.3 microM, respectively.
      Based on the parameters measured, a 72-hr exposure to 100 microM sambutoxin was
      not toxic to duckweed. Kudzu (Pueraria lobata L.) leaf disc assays revealed a
      similar trend in relative toxicities, but higher mycotoxin concentrations were
      required to elicit phytotoxic effects compared to duckweed. All four mycotoxins
      were cytotoxic to four mammalian cell cultures. However, in contrast to plants,
      wortmannin was the least toxic (IC50 = 10 to 20 microM) and sambutoxin exhibited
      a high level of toxicity (IC50 = 0.5 to 1 microM).

PMID- 12182538
TI  - Toxic pyrrolyzidine alkaloids from three mongolian plants. a possible risk for
      cattle poisoning.
AB  - Ten pyrrolizidine alkaloids (PA) were isolated from Senecio ambraceus, Senecio
      arcticus, and Nonea pulla growing on Mongolian pastures and meadows. Because of
      the contained toxic PA, these plants are suspected of causing cattle poisoning,
      which is reported in the literature and also in personal reports from local
      farmers and herdsmen. The structures of the PA were elucidated using
      spectroscopical methods. S. ambraceus contains the toxic PA senecionine,
      seneciphylline, and otosenine. In S. arcticus, senecionine can be found too,
      besides the non-toxic PA platyphylline, neoplatyphylline, and
      acetylplatyphylline. Nonea pulla is shown to contain the 0-7 isomers lycopsamine
      and intermedine as well as their 0-7-acetylderivatives. Besides the first
      mentioned acetylplatyphylline, all PA were already described in the literature.

PMID- 12182539
TI  - A reduced immunization scheme to obtain an experimental anti-Loxosceles laeta
      ("violinist spider") venom.
AB  - Bites by Loxosceles (L.) laeta spiders can produce severe envenomation in humans.
      The only specific treatment is the early administration of antivenom. The
      production of anti-Loxosceles antivenom is hampered by the extremely low venom
      yield by these spiders and by the difficulties in maintaining a large breeder of
      Loxosceles. We developed an experimental equinum L. laeta antivenom, using as
      immunogen venom glands homogenates from spiders captured in Argentina. Horses
      immunized with venom gland homogenate (1.0 mg total protein per horse) by the
      subcutaneous route were bled after completion of the immunization scheme. Plasma
      was fractionated by ammonium sulfate precipitation and treated with pepsin to
      obtain F(ab')2 fragments. The protein composition of the experimental antivenom
      was assessed by SDS-PAGE, and its immunochemical reactivity was compared with
      those of other anti-Loxosceles antivenoms available for therapeutic use in
      Argentina by ELISA and Western blot. The experimental, homologous anti-L. laeta
      antivenom appeared to be more efficient in neutralizing the lethal potency in
      mice and the necrotizing activity in rabbits than of the heterologous antivenom.

PMID- 12182540
TI  - Characterization of Habu thrombin-like enzyme (THLE) with a new n-terminal
      sequence from the venom of Trimeresurus flavoviridis (Habu).
AB  - A thrombin-like enzyme with a new amino-terminal sequence was isolated from the
      venom of Trimeresurus flavoviridis using Q-Sepharose, CM-Cellulose, and HW55
      column chromatographies. Homogeneity was confirmed by the formation of a single
      band in polyacrylamide gel electrophoresis. The enzyme has a molecular weight of
      29,000 Da. This thrombin-like enzyme was inhibited by p
      amidinophenylmethanesulfonyl fluoride hydrochloride (p-APMSF), and dithiothreitol
      (DTT) suggesting that serines and disulfide bonds are involved in the expression
      of the enzyme's clotting activity. This thrombin-like enzyme hydrolyzes the
      Aalpha-chain and Bbeta-chain of bovine fibrinogen. The enzyme was stable to heat
      treatment.

PMID- 12182541
TI  - Identification of tetrodotoxin in marine gastropods implicated in food poisoning.
AB  - Attempts were made to identify the toxin in the gastropod Zeuxis samiplicutus
      that was responsible for the recent food poisoning incidents in southern
      Zhejiang, Mainland China. Symptoms associated with the poisonings included
      paralysis, coma, vomiting, and aphasia. The remaining specimens of gastropod were
      assayed for tetrodotoxin toxicity (TTX). The range of specimen toxicity was found
      to be 4 - 186 mouse units (MU), and the average toxicity was 111 +/- 45 MU. The
      toxin was partially purified from the methanol extract of the gastropod by
      ultrafitration and Bio-Gel P-2 column chromatography. Cellulose acetate membrane
      electrophoresis, TLC, and HPLC analyses demonstrated that the toxin contained
      TTX. It was concluded that the causative agent of the above food poisoning was
      TTX.

PMID- 12182542
TI  - Comparative study of three short-chain neurotoxins from the venom of Naja
      kaouthia (Yunnan, China).
AB  - Three short-chain neurotoxins named NT-1, NT-II, and NT-III were purified from
      the venom of Naja kaouthia, a snake distributed throughout the south of Yunnan
      province, China, by a series of chromatographic steps, including an FPLC Resource
      S column. Their molecular weights, determined by matrix-assisted laser desorption
      ionization time-of-flight (MALDI-TOF) MS, were 6952.19 Da, 6854.92 Da, and
      6828.80 Da, respectively. NT-I consisted of 62 amino acid residues, and the other
      two consisted of 61 amino acid residues, including 8 cysteines. After hydrolysis
      by endoproteinase Glu-C, their primary sequences were determined. A test of their
      activities demonstrated that they effectively inhibited muscle contractions
      induced by electric stimulation. Furthermore, the extent of inhibition caused by
      NT-II and NT-III was less than that of NT-I. The IC50s were 0.04 microg/ml, 0.20
      microg/ml, and 0.23 microg/ml for NT-I, NT-II, and NT-III, respectively. Compared
      with NT-II and NT-III, the higher activity of NT-I may be a result of the amino
      acid residue substitution Ile36 to Arg36.

PMID- 12182544
TI  - Biological activities of skin secretions of the salamander Tylototriton
      verrucosus.
AB  - Water-soluble skin secretions of salamander Tylototriton verrucosus, first
      described by Anderson in 1871, were studied for their biological and enzymatic
      activities. They were found to be toxic to mice with an intraperitoneal LD50 of
      11.5 mg/kg. Using Sephadex G-75 gel filtration, it was proven that the toxic
      components of the secretions are proteins with molecular weights ranging from
      30,000 to 50,000 Da. The secretions of T. verrucosus display a wide spectrum of
      antimicrobial activities and also contain both proteolytic activity and trypsin
      inhibitory activity. In contrast, neither hemolytic nor hemorrhagic activities
      were found. The secretions were determined to have phospholipase A2 activity;
      however, no acetylcholine esterase activity was detectable under the assay
      conditions.

PMID- 12182543
TI  - Tezosentan inhibits both equinatoxin II and endotelin-1 induced contractions of
      isolated porcine coronary artery in a similar way.
AB  - In the present study we examined the endothelium-dependent mechanism in the
      constriction of the isolated porcine coronary artery induced by Equinatoxin II
      (EqT II). EqT II is a polypeptide isolated from the sea anemone (Actinia equina,
      L.). Contractions induced by endothelin-1 (ET-1) were compared with the
      contractions induced by EqT II. The force of contraction induced by 100 nM EqT II
      reached only 30% of the force of contraction induced by 100 nM ET-1. EC50 for ET
      1 was 5.14 nM, and for EqT II 101.1 nM. The effects of tezosentan, an endothelin
      ETA/B receptor antagonist, on contractions induced by either ET-1 or EqT II were
      compared. Tezosentan inhibited both ET-1 and, to a lesser extent, EqT II-induced
      contractions of isolated porcine coronary artery. Our present results confirm the
      involvement of endothelium in the EqT II-induced contractions of coronary
      arteries. The mode of action of tezosentan upon EqT II-induced contractions
      indicate that besides its pore-forming effect in the membranes, endothelium, and
      specifically endothelin-dependent mechanisms, are very important components of
      the toxin constrictory effects.

PMID- 12182545
TI  - Capacity of Thai green pit viper antivenom to neutralize the venoms of Thai
      Trimeresurus snakes and comparison of biological activities of these venoms.
AB  - The capacity of Thai green pit viper antivenom raised to Trimeresurus albolabris
      to neutralize the venoms from six species of Trimeresurus sp. in Thailand has
      been examined. They were Trimeresurus albolabris, T. macrops, T. popeiorum, T.
      hageni, T. purpureomaculatus, and T. kanburiensis. The antivenom neutralized
      lethal and hemorrhagic activities of all these venoms. The capacity of antivenom
      to neutralize lethal toxicity of the venom was expressed as the amounts (mg) of
      snake venom neutralized by 1 ml of the antivenom. The largest capacity was found
      with the homologous venom. Results of immunodiffusion, immunoblotting, and
      antigen-antibody complex formation experiments supported the results of
      neutralization experiments. Several biological activities of the Trimeresurus
      venoms were also examined and compared. They were lethal, hemorrhagic,
      proteolytic, phospholipase A, arginine ester hydrolyse, and thrombin activities.
      There was no correlation between the ratios of lethal toxicity and hemorrhagic
      activity, lethal toxicity and phospholipase A activity, as well as hemorrhagic
      activity and proteolytic activity.

PMID- 12182546
TI  - Amino acid sequence and biological properties of phospholipase A2-II from the
      venom of Agkistrodon bilineatus (Common Cantil).

PMID- 12182547
TI  - Surface analysis methods for characterizing polymeric biomaterials.
AB  - Surface properties have an enormous effect on the success or failure of a
      biomaterial device, thus signifying the considerable importance of and the need
      for adequate characterization of the biomaterial surface. Microscopy techniques
      used in the analysis of biomaterial surfaces include scanning electron
      microscopy, transmission electron microscopy, atomic force microscopy, and
      confocal microscopy. Spectroscopic techniques include X-ray photoelectron
      spectroscopy, Fourier Transform infrared attenuated total reflection and
      secondary ion mass spectrometry. The measurement of contact angles, although one
      of the earlier techniques developed remains a very useful tool in the evaluation
      of surface hydrophobicity/hydrophilicity. This paper provides a brief, easy to
      understand synopsis of these and other techniques including emerging techniques,
      which are proving useful in the analysis of the surface properties of polymeric
      biomaterials. Cautionary statements have been made, numerous authors referenced
      and examples used to show the specific type of information that can be acquired
      from the different techniques used in the characterization of polymeric
      biomaterials surfaces.

PMID- 12182548
TI  - Photoimmobilization of biomolecules within a 3-dimensional hydrogel matrix.
AB  - It has been recognized that a three-dimensional cell invasive scaffold that
      provides both topographical and chemical cues is desirable in regenerative tissue
      engineering to encourage cell attachment, migration, regrowth and ultimately
      tissue repair. Carbohydrate hydrogels are attractive for such applications
      because they are generally biocompatible and able to match the mechanical
      properties of most soft tissues. Although carbohydrate hydrogels have been
      previously modified with cell adhesive peptides and proteins, complicated
      hydrogel matrix activation was required prior to biomolecule coupling and,
      perhaps more importantly, the overall immobilization yield was low at
      approximately 1%. In this study, we report the photo-immobilization of a model
      biomolecule, ovalbumin (OVA), to agarose gel. We describe two methods of
      modification where the photoactive moiety is coupled to either the protein (i.e.
      OVA) or the matrix (i.e. agarose) prior to immobilization. We found that the
      photo-immobilization yield depends on the location of the photoactive moiety.
      Using photoactive OVA, 1.8% of the OVA initially incorporated into the agarose
      gel is immobilized; using photoactive agarose, 9.3% of the OVA initially mixed
      with the agarose is immobilized. The latter is a significant improvement over
      previous yields and may be useful in attaining our goal of immobilizing a
      biomolecule gradient for guided tissue regeneration.

PMID- 12182549
TI  - Glucose binding to molecularly imprinted polymers.
AB  - The main goal of this study was to prepare molecularly imprinted polymers (MIPs)
      with glucose recognition sites and to evaluate their glucose-binding properties
      for potential applications in glucose sensing and self-regulating insulin
      delivery devices. To mimic glucose-binding sites of natural proteins, monomers
      possessing functional groups similar to amino acids were used. Vinyl acetic acid
      (VAA), acrylamide (AAm), 4-pentenoic acid (PA), and allyl benzene (AB) were
      copolymerized with a cross-linking agent (N,N'-methylenebisacrylamide, BIS) in
      the presence of glucose as a template. The binding affinity of glucose to MIPs
      was examined by using an equilibrium dialysis technique. The dissociation
      constants of the MIPs were determined by Scatchard analysis. MIPs showed glucose
      binding affinity, while polymers synthesized in the absence of glucose template
      did not show a glucose-binding property. MIPs composed of VAA, AAm, PA, and AB at
      optimized mole ratios of monomers and cross-linker showed the highest glucose
      binding affinity, KD = 1.66 mM, which is comparable to that of a well-known
      glucose binding protein, concanavalin A (KD = 1.84 mM). The affinity between
      monomer and glucose was in the order VAA > AAm > AB > PA.

PMID- 12182550
TI  - The effect of oxidation on the enzyme-catalyzed hydrolytic biodegradation of
      poly(urethane)s.
AB  - Although the biodegradation of polyurethanes (PU) by oxidative and hydrolytic
      agents has been studied extensively, few investigations have reported on the
      combination of their effects. Since neutrophils (PMN) arrive at an implanted
      device first and release HOCl, followed by monocyte-derived macrophages (MDM)
      which have potent esterase activities and oxidants of their own, the combined
      effect of oxidative and hydrolytic degradation on radiolabeled polycarbonate
      polyurethanes (PCNU)s was investigated and compared to that of a polyester-PU
      (PESU) and a polyether-PU (PEU). The PCNUs were synthesized with PCN (MW =
      1,000), and butanediol (14C-BD) and one of two diisocyanates, hexane-1,6
      diisocyanate (14C-HDI) or methylene bis-p-phenyl diisocyanate (MDI). The PESU and
      PEU were synthesized using toluene-diisocyanate (14C-TDI), with polycaprolactone
      and polytetramethylene oxide as soft segments respectively, and ethylene diamine
      as the chain extender. The effect of pre-treatment with 0.1 mM HOC1 for 1 week on
      the HDI-based PCNUs and both TDI-based PUs resulted in a significant inhibition
      of radiolabel release (RR) elicited by cholesterol esterase (CE), when compared
      to buffer alone, whereas the MDI-based PCNU showed a small but significant
      increase. When PMN were activated on the HDI-based PCNU surface with phorbol
      myristate acetate (PMA), HOCl was released for 3 h, and was almost completely
      abolished by sodium azide (AZ). Simultaneously, the PMN-elicited RR, shown
      previously to be due to the esterolytic cleavage by serine proteases, was
      inhibited approximately 75% by PMA-activation of the cells, but significantly
      increased relative to the latter when AZ was added. Both in vitro oxidation by
      HOCl and the release of HOCI by PMN were associated with the inhibition of RR and
      suggest perturbations between oxidative and hydrolytic mechanisms of
      biodegradation.

PMID- 12182551
TI  - Novel dendrimer based polyurethanes for PEO incorporation.
AB  - A series of segmented polyurethanes based on methylene diisocyanate/poly
      (tetramethylene oxide) and chain extended with either ethylene diamine or butane
      diol in combination with a generation 2 polypropylenimine octaamine dendrimer
      were synthesized. For polymer synthesis, the dendrimers were protected with
      either t-boc or Fmoc groups and were incorporated into the polyurethane
      microstructure to permit further functionalization with biologically active
      groups. Following deprotection, the dendrimers were reacted with succinimidyl
      propionate polyethylene oxide (SPA-PEO) to improve the protein resistance of the
      polymers and to examine the potential of this technique for polymer
      functionalization. Different synthesis techniques were examined to optimize the
      incorporation of the PEO into the polymer microstructure. Incorporation of the
      dendrimers and the PEO were confirmed by NMR and FTIR. Gel permeation
      chromatography was used to examine the molecular weights of the various
      polyurethanes. The dendrimer incorporated polymers had significantly lower
      molecular weights than the ED or BDO chain extended controls, likely due to lower
      reactivity of the dendrimers as a result of steric factors. Following PEO
      reaction, the molecular weights of the resultant polymers were consistent with
      the levels of PEO incorporation noted by comparison of peak intensities in the
      NMR spectra. Due to the highly hydrophilic nature of the PEO, some migration to
      the polymer surface was expected. Water contact angles and XPS, used to
      characterize the surfaces, suggest that there was some PEO enrichment at the
      surface of the polymers. Adsorption of radiolabeled fibrinogen to the polymer
      surfaces was decreased by a factor of approximately 40% in some of the PEO
      incorporated polymers. There were also differences in the patterns of plasma
      protein adsorption on the various surfaces as evaluated by SDS PAGE and
      immunoblotting. Therefore, the use of dendrimers in biomaterials for
      incorporation of a large number of functional groups seems to be promising.

PMID- 12182552
TI  - Identification of biodegradation products formed by L-phenylalanine based
      segmented polyurethaneureas.
AB  - The degradation of novel biodegradable segmented polyurethanes was investigated
      with a view to determining the cleavage points within the polymer backbones
      targeted by the enzyme chymotrypsin. While the materials were developed with
      specific enzyme cleavage sites designed into the polymer chains, the nature of
      their degradation had not yet been determined. In this work, two segmented
      polyurethaneureas containing L-phenylalanine residues in the chain extender and
      two control polymers were subjected to degradation in the presence of
      chymotrypsin. Samples were collected for analysis over a time period from 1 day
      to 8 weeks. The degradation products from these materials were isolated using
      solid phase extraction and reversed phase high pressure liquid chromatography,
      and identified using mass and tandem mass spectrometry. Three hard segment
      related degradation products were identified and provide important insight into
      the polyurethane backbone cleavage sites. Cleavage of urea, ester and urethane
      bonds were observed. The results confirmed that chymotrypsin was able to cleave
      ester bonds adjacent to phenylalanine residues contained within the novel chain
      extender.

PMID- 12182553
TI  - Polyelectrolyte multilayer films modulate cytoskeletal organization in
      chondrosarcoma cells.
AB  - The aim of this study was to evaluate polyelectrolyte multilayer films as
      interfaces for implants. Polyelectrolyte multilayers were built up with different
      terminating layers by alternate deposition of oppositely charged polyelectrolytes
      on which chondrosarcoma (HCS-2/8) cells were grown in the presence of serum.
      Films formed by an increasing number of layers were investigated. The terminating
      layer was made of one of the following polyelectrolytes: poly-sodium-4
      styrenesulfonate (PSS), poly-L-glutamic acid (PGA), poly-allylamine hydrochloride
      (PAH), or poly(L-lysine) (PLL). Cell viability, inflammatory response, adherence,
      and cytoskeletal organization were studied. Induction of interleukin-8 (IL-8)
      secretion was detected on PAH and PLL ending polyelectrolyte films. Early
      cellular adherence was enhanced with PGA, PAH, PLL, and, to a lower extent, PSS
      terminating layers. Adherence was independent of the number of layers
      constituting the films. The presence of actin filaments and vinculin focal
      adhesion spots was observed on PSS or PAH ending films. They were respectively
      partially and totally absent on PGA and PLL terminating multilayer architectures.
      For PLL ending films, vinculin and actin organization was clearly dependent on
      the number of deposited layers. The results of this study suggest that PSS ending
      multilayered films constitute a good interfacial micro-environment at the
      material surface for HCS-2/8 cells.

PMID- 12182554
TI  - Fibrinogen adsorption by PS latex particles coated with various amounts of a
      PEO/PPO/PEO triblock copolymer.
AB  - Polystyrene (PS) latex particles of different sizes were adsorption coated with
      the polymeric surfactant Pluronic F108 (PEO129-PPO56-PEO129). The commercial
      surfactant was found to have a bimodal molecular weight distribution. However,
      the maximum surface concentrations resulting from adsorption of either the
      purified high molecular weight component or the composite were identical. An
      increase in the copolymer surface concentration on 252-nm particles was found to
      decrease their fibrinogen uptake exponentially. At maximum copolymer surface
      concentration, the fibrinogen uptake was two orders of magnitude lower than that
      of bare particles (down from 3.3 mg/m2 to 0.03 mg/m2). This surface protection
      was equally effective whether the adsorption involved the bimodal polymer
      surfactant or the purified high molecular weight fraction. The PEO tail mobility
      was investigated with electron paramagnetic resonance (EPR), and found to
      increase with an increase in polymer surface concentration. The comparatively
      slow motion of the PEO chains at low surface concentration indicated that not
      only the PPO block, but also the PEO blocks interacted hydrophobically with the
      PS surface. When the copolymer surface concentration was increased, the PEO tails
      were gradually being released, acquiring higher mobility as the surface became
      covered by the more strongly binding PPO blocks. Results obtained with F108
      coated particles of different sizes showed that particle size had a significant
      effect on the fibrinogen uptake, with larger particles showing larger fibrinogen
      uptakes.

PMID- 12182555
TI  - Cell adhesion behavior of chitosan surface modified by bonding 2
      methacryloyloxyethyl phosphorylcholine.
AB  - 2-Methacryloyloxyethyl phosphorylcholine (MPC)-bonded chitosan was prepared by
      Michael addition of MPC to the amino groups of chitosan. The modified surfaces
      were characterized by static contact angle and electron spectroscopy for chemical
      analysis (ESCA). The water contact angle of chitosan decreased with the MPC
      bonding and the rate of decrease depended on the amount of MPC bonding. ESCA
      analysis results proved that MPC had been bonded on the chitosan surface and the
      chitosan modified directly by MPC had a much higher concentration of MPC on the
      surface compared with that of MPC on chitosan modified indirectly by MPC. Cell
      adhesion tests indicated that a low concentration of MPC bonded chitosan was more
      favorable to cell adhesion while a high concentration of MPC bonded chitosan
      inhibited cell attachment.

PMID- 12182556
TI  - Morphology of poly(methacrylic acid)/poly(N-isopropyl acrylamide)
      interpenetrating polymeric networks.
AB  - The morphology of interpenetrating polymeric networks (IPNs) composed of the
      temperature-sensitive poly(N-isopropyl acrylamide) (PNIPAAm) and the pH-sensitive
      poly(methacrylic acid) (PMAA) were investigated by scanning electron microscopy
      (SEM). The IPN hydrogels were prepared by a sequential UV polymerization method.
      SEM studies were conducted on IPN hydrogel samples dried by different methods,
      and the influence on the IPN structure was discussed. The environmental
      conditions induced morphological changes for these dual sensitive IPN hydrogels
      which were studied by cryogenic SEM, when the gels were analyzed in their wet
      state. The results showed that the porous size in the IPN was strongly influenced
      by the environmental pH and temperature. Decrease in pH and increase in
      temperature resulted in significant pore size decrease for the swollen IPNs
      hydrogels.

PMID- 12182557
TI  - Physicochemical properties and in vitro biocompatibility of PEO/PTMO multiblock
      copolymer/segmented polyurethane blends.
AB  - A multiblock copolymer composed of poly(ethylene oxide) (PEO) and
      poly(tetramethylene oxide) (PTMO) and which forms a physical hydrogel was blended
      with Pellethane, a commercial segmented polyurethane (SPU) developed for various
      biomedical devices, to provide a PEO-rich surface with improved stability. The
      effect of the copolymer blending was evaluated with respect to surface
      hydrophilicity, long-term stability, mechanical properties, in vitro protein
      adsorption, and platelet adhesion. A small amount of the copolymer additive (5
      wt%) significantly improved surface hydrophilicity, which was then gradually
      enhanced by increasing the amount of the copolymer in the blends. The blend films
      exhibited minimal extraction of the copolymer additive when exposed to a buffer
      solution for 2 months at 37 degrees C, resulting in less than 1 wt% weight loss
      of the films even with 30 wt% content of the copolymer in the blends. Although a
      certain degree of alteration in the mechanical properties was observed by
      increasing the copolymer content, the mechanical properties were well maintained
      for up to 10 wt% addition of the copolymer, when compared with the bare SPU.
      Protein adsorption was significantly reduced with a small amount of copolymer
      additive as low as 5 wt%. Fibrinogen, an adhesive protein for further cellular
      adhesion and activation, was effectively repelled by increasing the amount of
      copolymer additive. The platelet adhesion test revealed that the blend film
      surface reduced platelet adhesion and the degree of inhibition was proportional
      to the content of the additive, up to 30 wt%. The high molecular weight (Mw =
      66,000) and compatible chemical structure of the copolymer with SPU made the
      surfaces PEO-rich and stable in an aqueous environment, resulting in an
      enhancement of the resistance to protein adsorption and platelet adhesion without
      a significant deterioration in physical properties.

PMID- 12182558
TI  - The effect of fluid shear and co-adsorbed proteins on the stability of
      immobilized fibrinogen and subsequent platelet interactions.
AB  - The conformation adopted by the plasma protein fibrinogen upon its adsorption
      onto synthetic surfaces has been implicated to play an important role in
      determining the blood compatibility of biomaterials. It has recently been shown
      that adsorbed fibrinogen undergoes biologically significant conformational
      changes with increasing residence time on the surface of selected biomaterials.
      The purpose of this study was to examine the effects of co-adsorbed proteins and
      shear forces on such time-dependent functional changes in fibrinogen adsorbed
      onto polyethylene (PE), polytetrafluoroethylene (PTFE), and silicone rubber (SR).
      Fibrinogen was adsorbed onto these materials for 1 min and then allowed to
      'reside' on these surfaces for up to 2 h prior to assessing its biological
      activity. Changes in fibrinogen reactivity were determined by measuring the
      adhesion of 51Cr-labeled platelets and the ability of blood plasma to displace
      previously adsorbed fibrinogen. The magnitude of platelet adhesion to substrates
      adsorbed with pure fibrinogen increased in the presence of shear, compared with
      static conditions; at the lowest shear rate of 200 s(-1), samples exhibited a 20
      fold increase in adhered platelet levels. In contrast, at a higher shear rate of
      1000 s(-1), the three polymers supported minimal levels of platelet attachment.
      Surfaces pre-adsorbed with 10% plasma did not promote a significant increase in
      the number of adherent platelets with increasing shear when compared with the
      pure fibrinogen-coated substrates. The presence of shear also significantly
      altered the materials' ability to retain fibrinogen. Under static conditions, the
      amount of fibrinogen retained following incubation in blood plasma increased on
      all materials with increasing fibrinogen residence time. However, the materials
      varied distinctly in their ability to retain adsorbed fibrinogen with increasing
      fibrinogen residence time, shear rate, and nature of the co-adsorbed proteins.
      Thus, the results from this study indicate that fluid shear, residence time of
      the adsorbed protein, nature of the co-adsorbed proteins, and surface chemistry
      of the material all play important roles in influencing platelet-surface
      interactions and that they act in a complex manner to influence the
      biocompatibility of a material.

PMID- 12182559
TI  - Poly(hydroxyethyl methacrylate-co-methacrylamidoalanine) membranes and their
      utilization as metal-chelate affinity adsorbents for lysozyme adsorption.
AB  - Different adsorbents have been reported in the literature for protein
      purification. The authors have developed a novel and new approach to obtain high
      protein adsorption capacity utilizing a 2-methacrylamidoalanine-containing
      membrane. Amino acid ligand 2-methacrylamidoalanine (MAAL) monomer was
      synthesized using methacryloyl chloride and alanine. Poly(2
      hydroxyethylmethacrylate-co-2-methacrylamidoalanine) [p(HEMA-co-MAAL)] membranes
      were then prepared by UV-initiated photopolymerization of HEMA and MAAL in the
      presence of an initiator (azobisisobutyronitrile, AIBN). The synthesized MAAL
      monomer was characterized by NMR. p(HEMA-co-MAAL) membranes were characterized by
      swelling studies, porosimeter, SEM, FTIR, and elemental analysis. These membranes
      have macropores in the size range of 5-10 microm. Cu(II) ions (25.9 mmol/m2) were
      chelated on these membranes. p(HEMA-co-MAAL) membranes were used to study the
      adsorption of lysozyme from aqueous media containing different amounts of
      lysozyme (0.1-3.0 mg/l) and at different pH values (4.0-8.0). The non-specific
      adsorption of lysozyme on the pHEMA membranes was negligible (0.9 microg/cm2).
      Incorporation of MAAL increased the lysozyme adsorption significantly up to 2.96
      mg/cm2. The lysozyme adsorption capacity of the Cu(II) incorporated membranes
      (9.98 mg/cm2) was greater than that of the p(HEMA-co-MAAL) membranes. More than
      90% of the adsorbed lysozyme was desorbed in 1 h in the desorption medium
      containing 1.0 M NaCl and 0.025 M EDTA. The metal-chelate affinity membranes are
      suitable for repeated use for more than ten cycles without a noticeable loss of
      capacity.

PMID- 12182561
TI  - Computational study of [10]annulene NMR spectra.
AB  - [reaction: see text] High-level theoretical methods are applied to calculate the
      13C NMR chemical shifts of three isomers of [10]annulene. Comparison with
      experiment clearly shows that the carrier of NMR signals of the so-called B form
      is the "twist" isomer. The results of this study strongly support predictions of
      relative energies of mono-trans [10]annulene isomers at the CCSD(T) level, which
      in turn are in qualitative disagreement with DFT and MP2 calculations.

PMID- 12182560
TI  - Co-culture of extracellular matrix suppresses the cell death of rat pancreatic
      islets.
AB  - The purpose of this study was to investigate the effect of culture
      microenvironment on the cell death of isolated rat pancreatic islets. After
      isolation by the conventional collagenase digestion technique, the islets were
      cultured in a hydrogel of collagen type I mixed with collagen type III, type IV,
      and laminin. Irrespective of the type of mixture, islet cell death was
      significantly suppressed by their co-culture with the collagen hydrogel mixtures,
      although no change in islet morphology was observed. Co-culture with the collagen
      mixtures had no influence on the expressed mRNA level of insulin, glucagon, and
      somatostatin of the islets, or the islet secretion of hepatocyte growth factor
      (HGF), interleukin (IL)-1alpha, and IL-1beta. These findings suggest that three
      dimensional culture in the collagen hydrogel and the mixture of laminin is able
      to maintain the cell viability of islets.

PMID- 12182562
TI  - A novel, stereoselective silyl-directed Stevens [1,2]-shift of ammonium ylides.
AB  - [reaction: see text] The silyl group of 2-silylpyrrolidines such as 1 plays
      several critical roles: a stereochemical control element in a facially selective
      carbenoid addition to the ring nitrogen, a stereochemical "placeholder" during
      regioselective 1,2-migration with retention by the resulting spirocyclic ammonium
      ylide, and a hydroxyl surrogate for an eventual stereoselective Fleming-Tamao
      oxidation. This chemistry represents a novel use of the Stevens rearrangement and
      offers a short, enantioselective route to hydroxylated quinolizidines such as 3
      from Boc-pyrrolidine.

PMID- 12182563
TI  - Copper(II) tetrafluoroborate catalyzed ring-opening reaction of epoxides with
      alcohols at room temperature.
AB  - [reaction: see text] Efficient ring opening of different epoxides by reaction
      with representative alcohols is presented. These processes were carried out at
      room temperature and rely on the usefulness of commercial copper
      tetrafluoroborate as catalyst.

PMID- 12182565
TI  - Ruthenium-catalyzed hydrosilylation of 1-alkynes with novel regioselectivity.
AB  - [reaction: see text] A ruthenium catalyst precursor bearing a bulky and electron
      donating pentamethylcyclopentadienyl (Cp) ligand, typically CpRuH3(PPh3),
      mediates hydrosilylation of several 1-alkynes with novel regioselectivity to give
      preferentially 2-silyl-1-alkenes.

PMID- 12182564
TI  - A novel approach to the synthesis of bicyclic lactones via an interrupted Nazarov
      reaction of gem-divinyl dihydrofurans.
AB  - [reaction: see text] A facile Lewis acid induced interrupted Nazarov reaction of
      gem-divinyl dihydrofurans to bicyclic lactones is described.

PMID- 12182566
TI  - Increased activity of in situ catalysts for alkyne metathesis.
AB  - [reaction: see text] Reaction of an enyne (1,1-diphenyl-pent-1-ene-3-yne) with a
      preheated mixture of Mo(CO)6/4-chlorophenol/3-hexyne at 130 degrees C furnished
      1,1,6,6-tetraphenylhex-1,5-diene-3-yne in an 80% yield. If the starting material
      was heated with a mixture of Mo(CO)6 and 4-chlorophenol under identical
      conditions, no reaction was observed.

PMID- 12182567
TI  - On the verge of axial chirality: atroposelective synthesis of the AB-biaryl
      fragment of vancomycin.
AB  - [structure: see text] Using the "lactone concept", differently substituted AB
      biaryl fragments (P)-2 (R = Me, t-Bu) of vancomycin have been synthesized
      atroposelectively. Their otherwise configurational instability was remedied by
      inclusion of two chlorine atoms in the B ring to give (M)-29. Starting from a
      still configurationally unstable lactone-bridged precursor, we obtained this
      biaryl with high atroposelectivity (dr 94:6) by ring cleavage with dynamic
      kinetic diastereomeric resolution.

PMID- 12182568
TI  - Silicon-tethered cyclocarbonylation of alkynes.
AB  - [reaction: see text] Temporary union of alkynes in the Fe(CO)5-promoted
      cyclocarbonylation provides a method for carbonylative cross-coupling of alkynes
      to construct unsymmetrically substituted cyclopentadienones.

PMID- 12182569
TI  - Total synthesis of proposed amphidinolide A via a highly selective ring-closing
      metathesis.
AB  - [structure: see text] A highly convergent synthesis of the proposed structure of
      amphidinolide A is reported. Instructive applications of several organometallic
      processes are illustrated, including a highly selective ring-closing metathesis
      reaction.

PMID- 12182570
TI  - Azaspirene: a novel angiogenesis inhibitor containing a 1-oxa-7-azaspiro[4.4]non
      2-ene-4,6-dione skeleton produced by the fungus Neosartorya sp.
AB  - [structure: see text] Azaspirene isolated from the fungus Neosartorya sp. is a
      novel angiogenesis inhibitor with a 1-oxa-7-azaspiro[4.4]non-2-ene-4,6-dione
      skeleton. Azaspirene inhibits the endothelial migration induced by vascular
      endothelial growth factor (ED100 = 27.1 microM).

PMID- 12182571
TI  - Carbon monoxide free aminocarbonylation of aryl and alkenyl iodides using DMF as
      an amide source.
AB  - [reaction: see text] Palladium-catalyzed coupling reaction of N,N
      dimethylformamide with aryl or alkenyl halides successfully proceeded in the
      presence of phosphoryl chloride to afford the corresponding tertiary amides in
      good yields.

PMID- 12182572
TI  - Intermolecular alkyne hydroaminations involving 1,1-disubstituted hydrazines.
AB  - [reaction: see text] Two readily prepared catalysts have been developed for the
      hydroamination of alkynes by 1,1-disubstituted hydrazines. The catalyses are
      facile with terminal alkynes and some internal alkynes. If the hydrazine bears an
      aryl group, Fischer cyclization can occur in a one-pot procedure. In addition,
      reactions with acetylene to produce a plethora of hydrazones are described.
      Catalytic reactions involving acetylene and substituted hydrazines are complete
      in less than 2 h at room temperature and 1 atm of pressure.

PMID- 12182574
TI  - Diastereoselective reduction of alkenylboronic esters as a new method for
      controlling the stereochemistry of up to three adjacent centers in cyclic and
      acyclic molecules.
AB  - [reaction: see text] cis-Boronates are readily available via a diastereoselective
      Pd-catalyzed reduction of tetrasubstituted alkenylboronic esters using H2.
      Applying the reaction conditions presented to unsaturated open-chain boronic
      esters allows the stereochemistry of up to three adjacent centers to be
      controlled.

PMID- 12182573
TI  - Modulation of boradiazaindacene emission by cation-mediated oxidative PET.
AB  - [reaction: see text] Bright green boradiazaindacene fluorescence is quenched by
      an oxidative photoinduced electron transfer (PET) from the excited state
      fluorophore to the bipyridyl unit complexed to metal cations. The closed shell
      diamagnetic cation Zn(II) is one of the most effective quenchers of fluorescence
      in this system, demonstrating that the quenching is not simply related to the
      facilitated intersystem crossing. The molecule also acts as a NOR logic gate with
      two chemical inputs, TFA and Zn(II).

PMID- 12182575
TI  - General method for the synthesis of caged phosphopeptides: tools for the
      exploration of signal transduction pathways.
AB  - [reaction: see text] An interassembly approach for the synthesis of peptides
      containing 1-(2-nitrophenyl)ethyl-caged phosphoserine, -threonine, and -tyrosine
      has been developed. Photochemical uncaging of these peptides releases the 2
      nitrophenylethyl protecting group to afford the corresponding phosphopeptide. The
      peptides described herein are based on phosphorylation sites of kinases involved
      in cell movement or cell cycle regulation and demonstrate the versatility of the
      method and compatibility with the synthesis of polypeptides, including a variety
      of encoded amino acids.

PMID- 12182576
TI  - Cyclic chiral silyl derivatives for the determination of the absolute
      configuration of aliphatic diols by gas chromatography.
AB  - [reaction: see text] Chiral bidentate silyl reagents have been developed for the
      GC analysis of aliphatic 1,3- and 1,4-diols. These reagents react with the diols
      to cyclic siloxanes, which allow the determination of their enantiomeric
      composition even in complex mixtures. The absolute configuration of 4,6
      nonadecanediol 7, occurring in the lipids of sunflower pollen, has been
      determined to be (4S,6R) by comparison with derivatized synthetic enantiomers.

PMID- 12182577
TI  - Recommendations for the evaluation of aromatic stabilization energies.
AB  - [reaction: see text] Perturbing influences, such as strain and the presence of
      heteroatoms, complicate the evaluation of aromatic stabilization energies (ASE).
      These complications are overcome easily by employing the "isomerization method".
      This is based on the differences (ISE) between total energies computed for only
      two species: a methyl derivative of the aromatic system and its nonaromatic
      exocyclic methylene isomer. The ISEs of benzene, pyridine, and naphthalene as
      well as the strained [5]paracyclophane, methano[10]annulene, and
      octadehydro[14]annulene are evaluated.

PMID- 12182578
TI  - Studies aimed at the total synthesis of azadirachtin. A modeled connection of C-8
      and C-14 in azadirachtin.
AB  - [reaction: see text] Studies on the connection between the right and left
      segments of azadirachtin are described. The Ireland-Claisen rearrangement of Li
      enolate of the modeled ester with dichlorodimethylsilane in toluene afforded the
      desired limonoid framework stereoselectively in good yield.

PMID- 12182579
TI  - Total synthesis of epi-otteliones.
AB  - [reaction: see text] Syntheses of 6-epi- and 8-epi-otteliones, corresponding to
      earlier proposed structures of the biologically potent natural product ottelione
      A, have been accomplished from the readily available Diels-Alder adduct of
      cyclopentadiene and p-benzoquinone.

PMID- 12182581
TI  - In situ generation of endohedral metallocenophanes of cobalt and rhodium with one
      cyclopentadienone unit.
AB  - [reaction: see text] Endohedral metallocenophanes of cobalt and rhodium were
      prepared using thermolysis of cyclopentadienylmetaldicarbonyl complexes bearing
      two alkyne units. In the case of the rhodium cyclopentadienonophanes, the
      structures of two isomeric complexes were confirmed by X-ray diffraction
      analysis.

PMID- 12182580
TI  - Improved functional group compatibility in the palladium-catalyzed synthesis of
      aryl amines.
AB  - [reaction: see text] The use of Pd2dba3 with bulky, electron-rich ligands 1 or 2
      and LiN(TMS)2 as the base for the coupling of amines with aryl halides containing
      hydroxyl, amide, or enolizable keto groups is described. This protocol expands
      the utility of palladium-catalyzed C-N bond formation by allowing for the use of
      aryl halides containing these functional groups, obviating the need for
      protecting group manipulations.

PMID- 12182582
TI  - Synthesis of tyrocidine A and its analogues by spontaneous cyclization in aqueous
      solution.
AB  - [reaction: see text] Head-to-tail cyclization of peptides is a multistep process
      involving tedious C-terminal activation and side chain protection. Here we report
      a facile, quantitative cyclization method in aqueous ammonia solution for the
      total syntheses of the cyclic decapeptide antibiotic Tyrocidine A and its
      analogues from their fully deprotected linear thioester precursors on a solid
      support. This novel aqueous method is conformation-dependent and may be
      applicable to syntheses of other natural cyclic peptides.

PMID- 12182583
TI  - Tripodal nitro-imidazolium receptor for anion binding driven by (C-H)+- - -X-
      hydrogen bonds.
AB  - [structure: see text] A positively charged tripodal receptor with nitro groups in
      the imidazolium rings was designed, synthesized, and characterized for its anion
      binding strength. The receptor shows strong affinity and high selectivity for Cl-
      through (C-H)+- - -X(-) hydrogen bonds wherein charge-charge and charge-dipole
      electrostatic interactions dominate. The association constant with chloride anion
      in a 9:1 mixture of acetonitrile-d3 and DMSO-d6 is measured to be 1.1 x 10(6) M(
      1). The receptor also shows reasonably high affinity toward H2PO4-.

PMID- 12182584
TI  - Calix[4]arene-functionalized naphthalene and perylene imide dyes.
AB  - [reaction: see text] Calix[4]arenes bearing one, two, or four 1,8-naphthyl imide
      groups at the wide rim and bis-calix[4]arenes connected via perylene-bisimide dye
      spacers have been synthesized. The low-temperature NMR spectrum of the
      tetranaphthylimide suggests, in agreement with a crystal structure, a C2
      symmetrical pinched cone conformation stabilized via face-to-face pi-pi
      interactions between opposite naphthylimide groups. UV-vis and fluorescence
      studies have been carried out for the perylene bis-calix[4]arene dyes.

PMID- 12182585
TI  - Ethyl 2-chlorooxazole-4-carboxylate: a versatile intermediate for the synthesis
      of substituted oxazoles.
AB  - [reaction: see text] By using a sequence of regiocontrolled halogenation and
      palladium-catalyzed coupling reactions, the synthesis of variously substituted
      oxazoles from ethyl 2-chlorooxazole-4-carboxylate (2) was accomplished. The
      methodology was applied to the synthesis of a series of 2,4-disubstituted, 2,5
      disubstituted, and 2,4,5-trisubstituted oxazoles.

PMID- 12182586
TI  - Theoretical elucidation on the antioxidant mechanism of curcumin: a DFT study.
AB  - [reaction: see text] Bond dissociation enthalpies (BDEs) for the curcumin-related
      compounds have been calculated using density functional theory (DFT) methods. It
      was found that the antioxidant mechanism of curcumin was a H-atom abstraction
      from the phenolic group, not from the central CH2 group in the heptadienone link.
      Curcumin, methylcurcumin, and half-curcumin had similar O-H BDEs, indicating that
      the two phenolic groups in curcumin were independent of each other.

PMID- 12182587
TI  - Total synthesis of the alkaloids martinelline and martinellic acid via a hetero
      Diels-Alder multicomponent coupling reaction.
AB  - [reaction: see text] A concise synthesis of the guanidine alkaloids, (+/-)
      martinelline and (+/-)-martinellic acid, using a protic acid catalyzed 2:1 hetero
      Diels-Alder coupling reaction between N-Cbz 2-pyrroline and methyl 4
      aminobenzoate, is described. Protic acid catalysis, rather than Lewis acid
      catalysis, was necessary to achieve the desired sense of diastereocontrol in the
      coupling reaction.

PMID- 12182588
TI  - pi-Ligands for generating transition metal-peptide complexes: coordination of
      amino acid derivatives to tungsten utilizing alkyne ligands.
AB  - [structure: see text] Amino acid derivatives bearing an alkyne (AA-CCH) at either
      the N- or C-terminus readily react with W(CO)3(S2CNMe2)2 to replace the carbon
      monoxides and form the novel bis-alkyne complexes W(AA-CCH)2(S2CNMe2)2; the
      solution behavior of these complexes shows that only the alkyne, and not the
      other functional groups on the amino acid, bonds to the tungsten.

PMID- 12182589
TI  - Total synthesis of batzelladine D.
AB  - [structure: see text] Stereoselective total synthesis of batzelladine D was
      accomplished in 15 steps. This synthesis features (i) successive 1,3-dipolar
      cycloaddition reactions to form the 2,5-disubstituted pyrrolidine ring system,
      (ii) esterification of the side chain to the bicyclic guanidine carboxylate, a
      common synthetic intermediate of batzelladine alkaloids, and (iii) tricyclic
      guanidine formation under the Mitsunobu reaction conditions.

PMID- 12182590
TI  - Concise total synthesis of (+/-)-aloperine and 6-epi-aloperine.
AB  - [reaction: see text] Total synthesis of aloperine and 6-epi-aloperine is
      reported. The crucial steps of the synthetic strategy are an aza-annulation
      reaction and an intermolecular Diels-Alder reaction. The synthetic plan proceeds
      from commercially available piperidine-2-ethanol.

PMID- 12182591
TI  - Lanthanide Lewis acid-mediated enantioselective conjugate radical additions.
AB  - [reaction: see text] Lanthanide triflates along with proline-derived ligands have
      been found to be efficient catalysts for enantioselective conjugate addition of
      nucleophilic radicals to enoates. N-Acyl oxazolidinones, when used as achiral
      additives, gave meaningful enhancements in the ees for the product.

PMID- 12182592
TI  - Enantioselective conjugate addition of silylketene acetals to beta
      enamidomalonates. Synthesis of beta-amino acid derivatives.
AB  - [reaction: see text] Conjugate addition of silylketene acetals or enolsilanes to
      enamidomalonates proceeds with excellent chemical efficiency and good selectivity
      using Cu(OTf)2 and a chiral bisoxazoline. The effect of the Lewis acid, ligand,
      the N-acyl substituent, and the nucleophile on yield and selectivity for the
      addition product have been evaluated.

PMID- 12182594
TI  - Total synthesis of (+/-)-mycoepoxydiene, a novel fungal metabolite having an
      oxygen-bridged cyclooctadiene skeleton.
AB  - [reaction: see text] The first total synthesis of (+/-)-mycoepoxydiene has been
      accomplished. A ring-closing olefin metathesis (RCM) approach was employed for
      the construction of the oxygen-bridged eight-membered bicyclic skeleton. The RCM
      product was converted to the target natural product featuring the oxidative
      rearrangement of a furfuryl alcohol introduced as the side chain and the
      stereoselective 1,2-reduction of a delta-keto-beta,gamma-unsaturated alpha-lactol
      intermediate.

PMID- 12182593
TI  - Measurement of enantiomeric excess using molecularly imprinted polymers.
AB  - [reaction: see text] A new method is presented for the measurement of
      enantiomeric excess (ee) utilizing molecularly imprinted polymers (MIPs). The
      method is demonstrated to be accurate and rapid, as the ee values can be
      calculated from straightforward concentration measurements. The MIP-based assay
      can also be adapted to measure the ee of samples of differing initial
      concentrations.

PMID- 12182596
TI  - Geometry and halogen regiochemistry determination of vicinal vinyl dihalides by
      1H and 13C NMR. Application to the structure elucidation of prefuroplocamioid, an
      unusual marine monoterpene.
AB  - Empirical rules based on 13C and 1H NMR spectroscopy to determine the
      regiochemistry and geometry of the 1,2-bromochloro vinyl portion of naturally
      occurring or synthetic compounds containing this functionality are proposed. The
      key feature of the method comes from the comparison of the spectral data of the
      new monoterpene metabolite, prefuroplocamioid, isolated from Plocamium
      cartilagineum, with those of other marine monoterpenes, as well as with some
      model compounds found in the literature.

PMID- 12182595
TI  - Synthesis of (+/-)-5-epi-citreoviral and (+/-)-citreoviral and the kinetic
      resolution of an allylic silane by a [3 + 2] annulation.
AB  - [reaction: see text] The [3 + 2] annulation reaction of allylsilane 1 with an
      alpha-keto ester provided the highly substituted tetrahydrofuran 2 as a single
      diastereomer in high yield. The synthesis of (+/-)-5-epi-citreoviral and (+/-)
      citreoviral has been accomplished with this annulation reaction as the key step.
      Using the pantolactone-derived alpha-keto ester, the allylsilane 1 has been
      resolved with high enantiomeric purity.

PMID- 12182598
TI  - Tandem carbon-carbon bond constructions via catalyzed cyanation/Brook
      rearrangement/C-acylation reactions of acylsilanes.
AB  - [reaction: see text] A tandem nucleophile-catalyzed cyanation/Brook
      rearrangement/C-acylation has been developed. Phase transfer cocatalysts
      facilitate cyanide-catalyzed reactions between acylsilanes and cyanoformates to
      afford protected tertiary carbinol products. A catalytic cycle is proposed
      involving cyanation of an acylsilane, [1,2]-Brook rearrangement, and C-acylation
      of the derived carbanion by a cyanoformate ester. The reaction offers an
      efficient method for the preparation of functionalized, unsymmetrical malonic
      acid derivatives.

PMID- 12182597
TI  - A divergent approach to the myriaporones and tedanolide: completion of the carbon
      skeleton of myriaporone 1.
AB  - [reaction: see text] A linear but concise synthetic approach toward the
      structurally related natural products myriaporone and tedanolide is reported. The
      route is highlighted by a stereoselective homoallenylboration and a regio- and
      chemoselective nitrile oxide cycloaddition. Installation of the (Z)-olefin
      completed the carbon skeleton of myriaporone 1.

PMID- 12182599
TI  - Microwave-accelerated O-alkylation of carboxylic acids with O-alkylisoureas.
AB  - [reaction: see text] Microwave-assisted O-alkylations of several carboxylic acids
      have been performed with three different O-alkylisoureas. All reactions are
      significantly faster compared to conventionally heated reactions, while retaining
      high chemoselectivity. The combination of microwave technology with the use of
      the solid-supported isourea 3 enables the synthetic chemist to obtain the pure
      methyl esters starting from the corresponding acids in less than an hour.

PMID- 12182600
TI  - Short total synthesis of 8,10-di-O-methylbergenin.
AB  - [reaction: see text] A short, high-yielding synthesis of the C-glucoside 8,10-di
      O-methylbergenin is reported. Key elements of the synthesis are a stereoselective
      installation of a beta-C-aryl linkage, a palladium(0)-catalyzed aryl
      carbonylation, and a regioselective lactonization reaction. This pathway should
      allow access to a host of bergenin analogues.

PMID- 12182601
TI  - A [2 + 2] cycloaddition route to dimethylaminomethylene vinamidinium salts.
AB  - [reaction: see text] Trifluoropropanoic acid reacts with 1 equiv of POCl3 in DMF
      to generate the trifluoromethyl enamine (7). At this stage, two reaction
      manifolds are available. The expected reaction with additional POCl3 generates
      the 2-trifluoromethyl vinamidinium salt (3c). However, thermally driven loss of
      fluoride generates an iminium ion, which sets the stage for a [2 + 2]
      cycloaddition to ultimately generate the dimethylaminomethylene vinamidinium salt
      (1).

PMID- 12182602
TI  - Ligand-free palladium catalysis of the Suzuki reaction in water using microwave
      heating.
AB  - [reaction: see text] We report the ligand-free palladium catalysis of the Suzuki
      reaction in water using microwave heating. Our methodology uses low palladium
      loadings (0.4 mol %), is fast (5-10 min reaction time), and is useful for
      couplings involving boronic acids and aryl iodides, bromides, and chlorides.

PMID- 12182604
TI  - Total synthesis of gambierol.
AB  - [structure: see text] The first total synthesis of gambierol, a marine polycyclic
      ether toxin, has been achieved. The synthesis features the Pd(PPh3)4/CuCl/LiCl
      promoted Stille coupling for the stereoselective construction of the sensitive
      triene side chain that includes a conjugated (Z,Z)-diene moiety.

PMID- 12182603
TI  - Highly stereoselective and stereodivergent synthesis of four types of THF cores
      in acetogenins using a C4-chiral building block.
AB  - [reaction: see text] Four stereoisomers of the THF cores, synthetic intermediates
      of acetogenins, have been synthesized with high diastereoselectivity by
      asymmetric alkynylation and subsequent stereodivergent THF ring formation. The
      asymmetric alkynylation of alpha-oxyaldehyde with (S)-3-butyne-1,2-diol
      derivatives (C4-unit) gave good yields of syn and anti adducts with >97:3 dr and
      94:6 dr, respectively. These adducts were converted into the four types of THF
      compounds via one-pot THF formation or via intramolecular Williamson synthesis.

PMID- 12182606
TI  - Tuning the reaction paths in palladium(0)-catalyzed coupling-cyclization reaction
      of beta-amino allenes with organic halides: a substituent switch.
AB  - [reaction: see text] Substituent effects on the allene moiety and the N
      protecting group were found to be the dominant factor in determining the reaction
      paths in the Pd(0)-catalyzed coupling-cyclization reaction of beta-amino allenes
      with organic halides.

PMID- 12182605
TI  - The first example of enantioselective allyl transfer from a linear homoallylic
      alcohol to an aldehyde.
AB  - [reaction: see text] The first example of enantioselective linear homoallylic
      alcohol transfer reaction was revealed. In all cases, the whole rearrangement is
      thermodynamically favorable and a steric effect is the driving force of this
      reaction. The preservation of the stereocenter and olefin geometry together with
      the isolation of gamma-adduct homoallylic alcohols in one isomeric form have
      warranted the proposed mechanism.

PMID- 12182607
TI  - Trans-hydrometalation of alkynes by a combination of InCl3 and DIBAL-H: one-pot
      access to functionalized (Z)-alkenes.
AB  - [reaction: see text] Triethylborane-induced hydrometalation of alkynes proceeds
      in an anti manner to afford the corresponding (Z)-alkenylmetal compounds
      stereoselectively, where dichloroindium hydride would play a key role. A variety
      of functional groups including hydroxy, carbonyl, and carboxy groups were
      tolerant under the reaction conditions. Following iodolysis and cross-coupling
      reaction of the (Z)-alkenylmetal species show the usefulness of this strategy.

PMID- 12182608
TI  - An amphiphilic resin-supported palladium catalyst for high-throughput cross
      coupling in water.
AB  - [reaction: see text] The Suzuki-Miyaura coupling of aryl halides (8 varieties)
      and aryl- or vinylboronic acids (12 varieties) took place in water in the
      presence of a palladium complex of an amphiphilic polystyrene-poly(ethylene
      glycol) copolymer resin-supported N-anchored 2-aza-1,3
      bis(diphenylphosphino)propane ligand and potassium carbonate to give uniform and
      quantitative yields of the corresponding biaryls (96 varieties).

PMID- 12182609
TI  - A simple and advantageous protocol for the oxidation of alcohols with O
      iodoxybenzoic acid (IBX).
AB  - [reaction: see text] An efficient, user-friendly procedure for the oxidation of
      alcohols using IBX is described. Simply heating a solution of the alcohol in the
      presence of suspended IBX followed by filtration and removal of the solvent gives
      excellent yields of the corresponding carbonyl compounds. We illustrate this
      procedure with a panel of primary and secondary alcohol substrates and note that
      it allows recycling and reuse of the oxidant.

PMID- 12182611
TI  - Biomimetic cycloaddition approach to tropolone natural products via a tropolone
      ortho-quinone methide.
AB  - [reaction: see text] A study toward a possible biomimetic hetero Diels-Alder
      reaction is reported between humulene and a novel tropolone ortho-quinone
      methide. A suitable tropolone ortho-quinone methide precursor has been prepared
      from 3-methyl-2-furoate. Heating the ortho-quinone methide precursor gave a
      tropolone ortho-quinone methide, which in the presence of humulene underwent a
      hetero Diels-Alder reaction to give a deoxy analogue of epolone B.

PMID- 12182610
TI  - Synthesis of (-)-pinolidoxin: divergent synthetic strategy exploiting a common
      silacyclic precursor.
AB  - [reaction: see text] We describe a highly convergent and efficient synthesis of (
      )-pinolidoxin, a potent modulator of plant pathogenesis, providing unambiguous
      determination of the relative and absolute stereostructure of this highly
      oxygenated fungal metabolite. Our unique strategy highlights the applications of
      novel silacyclic precursors for stereocontrolled polyol synthesis and features
      the finding of the reversible ring-closing metathesis.

PMID- 12182612
TI  - New and convenient method for incorporation of pentafluorosulfanyl (SF5)
      substituents into aliphatic organic compounds.
AB  - [reaction: see text] Use of Et3B as a catalytic initiator allows the convenient,
      regiospecific, and highly stereoselective addition of SF5Cl in high yield to a
      variety of alkenes and alkynes.

PMID- 12182616
TI  - Stereoselective synthesis of annular 9-cis-retinoids and binding characterization
      to the retinoid X receptor.
AB  - Analogues of 9-cis-retinoic acid incorporating an alicyclic ring between the C19
      and C10 positions have been synthesized and evaluated as ligands for the RXRalpha
      nuclear receptor. The stereocontrolled synthesis of these configurationally
      constrained retinoids combines a Stille cross-coupling and the Wittig reaction as
      key bond-forming steps. The palladium-catalyzed cross-coupling reaction of the
      beta-bromo-alpha,beta-unsaturated aldehydes 5 to dienylstannane 6 is very fast at
      room temperature, and takes place with preservation of the dienylstannane
      geometry. A highly stereoselective Wittig reaction afforded the C7-C8 bond
      connecting the hydrophobic ring to the retinoid side chain. The binding
      affinities of these compounds for the receptor were determined, and the
      structural and energetic rationale behind the affinity profile of the cyclic 9
      cis-retinoic acid derivatives for the RXRalpha nuclear receptor was characterized
      by using Molecular Mechanics protocols.

PMID- 12182615
TI  - A highly effective nonpolar isostere of deoxyguanosine: synthesis, structure,
      stacking, and base pairing.
AB  - We describe the preparation and structure of the deoxyribonucleoside of 4-fluoro
      6-methylbenzimidazole, abbreviated dH (8), which acts as a close shape mimic of
      the nucleoside deoxyguanosine. The nucleoside is prepared from 2-fluoro-4
      methylaniline in seven steps. The X-ray crystal structure reveals a (-sc)
      glycosidic orientation, an S conformation for the deoxyribose moiety, and quite
      close shape mimicry of guanine by the substituted benzimidazole. Conformational
      studies by (1)H NMR and (1)H-(1)H ROESY experiments reveal an S-type conformation
      and an anti glycosidic orientation in solution (D(2)O), essentially the same as
      that of deoxyguanosine. Base-stacking studies in a "dangling end" context reveal
      that the benzimidazole base mimic stacks more strongly than all four natural
      bases, and more strongly than its counterpart guanine by 1.1 kcal/mol. Base
      pairing studies in a 12mer DNA duplex show that, like other nonpolar nucleoside
      isosteres, H is destabilizing and nonselective when paired opposite natural
      bases. However, when paired opposite another nonpolar isostere, difluorotoluene
      (F), a mimic of thymine, the pair exhibits stability approaching that of its
      natural analogue, a G-T (wobble) base pair. The nucleoside analogue dH will be
      useful in studies of protein-DNA interactions, and the H-F base pair will serve
      as a structurally and thermodynamically close mimic of G-T in studies of DNA
      mismatch repair enzymes.

PMID- 12182617
TI  - A cassette ligation strategy with thioether replacement of three Gly-Gly peptide
      bonds: total chemical synthesis of the 101 residue protein early pregnancy factor
      [psi(CH(2)S)28-29,56-57,76-77].
AB  - The 101 residue protein "early pregnancy factor" (EPF), also known as human
      chaperonin 10, was synthesized from four functionalized, but unprotected, peptide
      segments by a sequential thioether ligation strategy. The approach exploits the
      differential reactivity of a peptide-NHCH(2)CH(2)SH thiolate with XCH(2)CO
      peptides, where X = Cl or I/Br. Initial model studies with short functionalized
      (but unprotected) peptides showed a significantly faster reaction of a peptide
      NHCH(2)CH(2)SH thiolate with a BrCH(2)CO-peptide than with a ClCH(2)CO-peptide,
      where thiolate displacement of the halide leads to chemoselective formation of a
      thioether surrogate for the Gly-Gly peptide bond. This rate difference was used
      as the basis of a novel sequential ligation approach to the synthesis of large
      polypeptide chains. Thus, ligation of a model bifunctional N(alpha)-chloroacetyl,
      C-terminal thiolated peptide with a second N(alpha)-bromoacetyl peptide
      demonstrated chemoselective bromide displacement by the thiol group. Further
      investigations showed that the relatively unreactive N(alpha)-chloroacetyl
      peptides could be "activated" by halide exchange using saturated KI solutions to
      yield the highly reactive N(alpha)-iodoacetyl peptides. These findings were used
      to formulate a sequential thioether ligation strategy for the synthesis of EPF, a
      101 amino acid protein containing three Gly-Gly sites approximately equidistantly
      spaced within the peptide chain. Four peptide segments or "cassettes" comprising
      the EPF protein sequence (BrAc-[EPF 78-101] 12, ClAc-[EPF 58-75]-[NHCH(2)CH(2)SH]
      13, ClAc-[EPF 30-55]-[NHCH(2)CH(2)SH] 14, and Ac-[EPF 1-27]-[NHCH(2)CH(2)SH] 15)
      of EPF were synthesized in high yield and purity using Boc SPPS chemistry. In the
      stepwise sequential ligation strategy, reaction of peptides 12 and 13 was
      followed by conversion of the N-terminal chloroacetyl functional group to an
      iodoacetyl, thus activating the product peptide for further ligation with peptide
      14. The process of ligation followed by iodoacetyl activation was repeated to
      yield an analogue of EPF (EPF psi(CH(2)S)(28)(-)(29,56)(-)(57,76)(-)(77)) 19 in
      19% overall yield.

PMID- 12182618
TI  - The periodic table and the intrinsic barrier in s(n)2 reactions.
AB  - The identity S(N)2 reactions on nitrogen (see eq 3) with nucleophiles having the
      general structure H(n)()X(-) where X belongs to the group of nonmetallic elements
      which do not border the line separating them from the metallic elements (X = F,
      Cl, Br, I, O, S, Se, N, P, and C) were studied at the G2+ level. The results show
      that, similarly to the previously observed phenomenon for S(N)2 reaction on
      carbon (J. Am. Chem. Soc. 1999, 121, 7724), the Periodic Table, through the
      valence of the element X, controls the intrinsic barrier for the reaction. The
      average intrinsic barriers obtained for nitrogen substrates were 20, 27, 39, and
      57 kcal/mol for the mono-, di-, tri-, and tetravalent X's, respectively. It is
      also concluded that the intrinsic barriers are similar for N- and C-based
      substrates and dimethyl substitution on both raises the intrinsic barrier by ca.
      10 kcal/mol.

PMID- 12182619
TI  - Synthesis of mayolene-16 and mayolene-18: larval defensive lipids from the
      European cabbage butterfly.
AB  - A tandem Wittig approach has been employed for the synthesis of both
      (11S,9Z,12Z,15Z)- and (11R,9Z,12Z,15Z)-hydroxyoctadeca-9,12,15-trienoic acid (11
      hydroxylinolenic acid, 11-HLA) from (R)-glyceraldehyde acetonide. From (11R)-HLA
      we have prepared the corresponding palmitic acid and stearic acid esters,
      mayolene-16 (1) and mayolene-18 (2), insect defensive compounds recently
      identified from Pieris rapae larvae. In addition, we describe the synthesis of
      three macrocyclic oligomers (24-26) derived from (11R)-HLA.

PMID- 12182620
TI  - Synthesis and self-inclusion of bipyridine-spaced cyclodextrin dimers.
AB  - The synthesis and conformational behavior of two cyclodextrin dimers containing
      aromatic bipyridine spacers is presented. The proton NMR spectra of these dimers
      in aqueous solution show a doubling of signals in the aromatic region due to
      complete or partial self-inclusion of the spacer. The degree and the strength of
      self-inclusion is dependent on the substitution pattern of the bipyridine unit.
      This unexpected difference in the self-inclusion behavior is revealed by 2D NOESY
      and circular dichroism spectra.

PMID- 12182621
TI  - Anionic cycloaromatization of 1-aryl-3-hexen-1,5-diynes initiated by methoxide
      addition: synthesis of phenanthridinones, benzo[c]phenanthridinones, and biaryls.
AB  - Treatment of 2-((Z)-6-substituted-3-hexene-1,5-diynyl)benzonitriles with sodium
      methoxide in refluxing methanol in the presence of a polar aprotic solvent, such
      as DMSO, HMPA, THF, or 18-crown-6, gave phenanthridinones in 21-77% yields. In
      these cases, addition of 10% DMSO into the reaction mixture gave the highest
      yield. On the other hand, methanolysis of 2-(2-(2
      alkynylphenyl)ethynyl)benzonitriles under the same reaction conditions gave
      benzo[c]phenanthridinones in 31-57% yields. Methanolysis of (Z)-1-aryl-3-hexen
      1,5-diynes in the presence of 2 equiv of tetrabutylammonium iodide gave biaryls
      in 14-64% yields. It is found that the reactions with aryl groups bearing
      electron-withdrawing groups proceeded at greater rates and gave better yields.

PMID- 12182622
TI  - Synthesis of chiral pilocarpine analogues via a C-8 ketone intermediate.
AB  - The synthesis of a chiral pilocarpine analogue 3 in which the lactone ring is
      replaced by an oxazolidinone and the bridging methylene group is in the ketone
      oxidation state has been accomplished. The utility of this compound as a key
      intermediate for the preparation of more complex structures was demonstrated by
      its reduction to two alcohol epimers and its reaction with a methylene ylide.

PMID- 12182624
TI  - Tandem Pummerer/Mannich cyclization cascade of alpha-sulfinylamides as a method
      to prepare aza-heterocycles.
AB  - A series of alpha-sulfinylenamides was conveniently prepared by the condensation
      of a primary amine with a ketone, followed by reaction of the resulting imine
      with ethylsulfenylacetyl chloride and subsequent oxidation with sodium periodate.
      When treated with p-TsOH, cyclization occurred to produce fused isoquinoline
      lactams by a mechanism that involves an initial Pummerer reaction followed by a
      subsequent cyclization of the resulting N-acyliminium ion onto the tethered
      aromatic ring. The isolation of a single diastereomer was rationalized in terms
      of a Nazarov-type 4pi-electrocyclic reaction followed by pi-cyclization onto the
      least hindered side of the N-acyliminium ion. Another method that was used to
      generate the alpha-acylthionium ion intermediate involved the reaction of
      bis(ethylsulfenylacetyl)acetamides with dimethyl(methyl)thiosulfonium
      tetrafluoroborate (DMTSF). Treatment of several bis-ethylsulfenylenamides with
      DMTSF delivered novel spiro-heterocycles as single diastereomers in good yield by
      a related process. The convergency and stereochemical control associated with
      this cascade sequence make it particularly suited for the assembly of natural
      product scaffolds. Some preliminary studies were directed toward both mesembrine
      and deethylibophyllidine. When the model Z-enamido sulfoxide 33 was heated with p
      TsOH, a 80% yield of tosylate 34 was obtained as a single diastereomer. In this
      case, the carbocation intermediate derived from cyclization onto the terminal pi
      bond was trapped with p-TsOH from the least hindered face, opposite the angular
      carbomethoxy and methyl groups. Related cyclization cascades were also found to
      occur with systems containing tethered indole rings.

PMID- 12182623
TI  - Stereoselective synthesis of the beta-anomer of 4'-thionucleosides based on
      electrophilic glycosidation to 4-thiofuranoid glycals.
AB  - Three types of 4-thiofuranoid glycal with different 3,5-O-silyl protecting groups
      were prepared and their electrophilic glycosidation was investigated. The 3,5-bis
      O-(tert-butyldimethylsilyl)-4-thiofuranoid glycal (5) was obtained through
      mesylation of 2-deoxy-4-thio-D-erythro-pentofuranose (4) and subsequent base
      promoted elimination, while thermal elimination of sulfoxide derivatives was
      suitable for the preparation of 3,5-O-(tetraisopropyldisiloxane-1,3-diyl) (9) and
      3,5-O-(di-tert-butylsilylene) (11) 4-thioglycals. The glycosidation reactions of
      these 4-thioglycals were carried out, in the presence of either PhSeCl or NIS, by
      using silylated derivatives of uracil, thymine, cytosine, and N(6)
      benzoyladenine. Among the three 4-thioglycals, 11 was found to be an excellent
      glycosyl donor, forming the desired beta-anomer exclusively irrespective of the
      nucleobase employed.

PMID- 12182626
TI  - Alkylation of dihydrofullerenes.
AB  - The fulleride dianions C(60)(2-) and C(70)(2-) were generated by deprotonation of
      the corresponding hydrogenated fullerenes, 1,2-C(60)H(2) and 1,2-C(70)H(2). These
      anions were prepared in the presence of a variety of alkylating agents, and mono-
      or dialkylated products were obtained. Alkylation was not successful with
      sulfonate ester alkylating agents. Deprotonation of monoalkylated compounds,
      followed by second alkylation with a different alkylating agent, produced
      heterodialkylated compounds. The monoalkyated material was invariably the 1,2
      isomers, while the dialkylated materials were generally 1,4-isomers, although
      some 1,2-isomer was observed in the C(70) context. The major product from
      alkylation of C(70)(2-) was the 7,23-isomer 13a, a structure where the alkylation
      took place near the equator of the fullerene cage, rather than at the more
      strained carbons near the poles.

PMID- 12182627
TI  - Gamma-hydroxy-alpha,beta-alkenenitriles: chelation-controlled conjugate
      additions.
AB  - Temporarily anchoring Grignard and organolithium reagents to gamma-hydroxy
      alpha,beta-alkenenitriles promotes efficient conjugate additions to what are
      otherwise recalcitrant Michael acceptors. Sequential deprotonation and addition
      of a modest excess of a second Grignard reagent allows effective conjugate
      delivery of alkyl groups to cyclic and acyclic alkenenitriles. Mechanistically,
      conjugate additions proceed through alkylmagnesium alkoxide complexes for all but
      the more substituted alkenenitriles that require alkyl transfers from the more
      reactive ate complexes. Synthetically, chelation-controlled conjugate additions
      rapidly, and stereoselectively, assemble substituted nitriles, installing up to
      two new stereocenters in a single synthetic operation.

PMID- 12182628
TI  - Lewis acid-promoted synthesis and reactivity of beta-O-benzylhydroxylamino imides
      derived from D-glyceraldehyde.
AB  - This paper describes the synthesis and use of beta-hydroxylamino imides derived
      from D-glyceraldehyde possessing a number of reactive sites that operate
      synergistically or alternatively to bring about highly regio- and
      diastereoselective transformations to give an optically pure aziridine-2-imide, a
      dihydro pyrimidine-2,4-dione, or a lactone. Both the syntheses, via the
      diastereoselective 1,4-conjugate addition of O-benzyl hydroxylamine to alpha,beta
      unsaturated imides, and transformations can be simply tuned by choosing between
      different Lewis acids.

PMID- 12182625
TI  - Enantioselective synthesis of bicyclo[3.1.0]hexane carbocyclic nucleosides via a
      lipase-catalyzed asymmetric acetylation. Characterization of an unusual acetal
      byproduct.
AB  - The bicyclo[3.1.0]hexane scaffold can lock the conformation of a carbocyclic
      nucleoside into one of the two antipodal (north or south) conformations typical
      of conventional nucleosides that normally exist in a rapid, two-state equilibrium
      in solution. In a recent brief communication, we reported a practical method to
      access the requisite bicyclo[3.1.0]hexane pseudosugar for the north antipode via
      an intramolecular olefin-ketocarbene cycloaddition. The most attractive features
      of this synthesis was that a relatively complex synthon was obtained from simple
      and inexpensive starting materials and that the resulting racemic mixtures of
      purine nucleosides could be successfully resolved by adenosine deaminase (ADA)
      hydrolysis. In this work, we describe the development of a more general, lipase
      catalyzed double-acetylation reaction, which could successfully resolve an
      earlier precursor, 4-(tert-butyldiphenylsilamethoxy)-1
      (hydroxymethyl)bicyclo[3.1.0]hexan-2-ol [(+/-)-7], into enantiomerically pure (+)
      diacetate 8 and (-)-monoacetate 9. The former diacetate was converted to the
      conformationally locked (north)-carbocyclic guanosine (+)-17 identical to the one
      obtained previously by ADA resolution. The present method represents a more
      general and efficient process applicable to the synthesis of all classes of
      (north) bicyclo[3.1.0]hexane nucleosides, including pyrimidine analogues. During
      the lipase-catalyzed resolution, we were able to demonstrate the presence of an
      unusual acetal-forming reaction that consumed small amounts of the unreactive
      monoacetate (-)-9. This side reaction was also enzyme-catalyzed and was triggered
      by the byproduct acetaldehyde generated during the reaction.

PMID- 12182629
TI  - Anion binding by fluorescent biimidazole diamides.
AB  - Six 2,2'-biimidazoles with various amide groups at the 4- and 4'-positions were
      prepared from 5-propyl-1H-imidazole-4-carboxylic acid ethyl ester. In the final
      step of the synthesis, biimidazole C2-C2' bond formation was accomplished in 33
      45% yield by palladium(0)-catalyzed homocoupling of the corresponding 2
      iodoimidazoles. Four of the biimidazoles were studied by X-ray diffraction. In
      the solid state, all display coplanar imidazole rings, an anti relationship of
      amide groups, and intramolecular (NH(amide).N(imid)) and intermolecular
      (NH(imid).O(amide)) hydrogen bonding. In CH(2)Cl(2), the emission intensity of
      the biimidazoles is quenched by the presence of dihydrogenphosphate and chloride
      anions, but no shifts in lambda(emiss) are observed. Binding constants for 1:1
      biimidazole-anion complexation (K(assoc)) are on the order of 10(4) M(-)(1) for
      H(2)PO(4)(-) and Cl(-). One of the receptors (bearing 3,5-difluorobenzylamides)
      is selective for chloride. The participation of the amide NH atoms in anion
      binding was established by (1)H NMR.

PMID- 12182631
TI  - Palladium-catalyzed aminoallylation of activated olefins with allylic halides and
      phthalimide.
AB  - The three-component aminoallylation reaction of the activated olefins 2 with the
      phthalimide 1a and allyl chloride proceeded very smoothly in the presence of
      Pd(2)dba(3).CHCl(3) (5 mol %)/P(4-FC(6)H(4))(3) (40 mol %) and Cs(2)CO(3) (3
      equiv against 2) in dichloromethane at room temperature to give the corresponding
      aminoallylated products, N-pent-4-enylphthalimides 3, in 58-99% yields. The
      reaction of oxazolidinone 1b also proceeded very smoothly to give N-(2,2-dicyano
      1-phenylpent-4-enyl)oxazolidinone in a quantitative yield; however, the Tsuji
      Trost-type allylation products 4 were obtained in the case of dibenzylamine, N
      tosylaniline, and pyrrolidin-2-one. Further, 2 underwent cycloaddition with N
      tosylvinylaziridine 9a in the presence of Pd(2)dba(3).CHCl(3) (5 mol %)/P(4
      FC(6)H(4))(3) (40 mol %) in THF at room temperature, giving the corresponding
      pyrrolidines 11 in 69-99% yields.

PMID- 12182630
TI  - First total syntheses of the phytotoxins solanapyrones D and E via the domino
      Michael protocol.
AB  - The phytotoxins solanapyrones D (1) and E (2) have been synthesized from the
      decalone prepared by the domino Michael reaction of the kinetic enolate of
      optically pure acetylcyclohexene with methyl crotonate. The decalone was
      transformed into a solanapyrone core by equilibration into thermodynamically
      stable trans-decalone (11), dehydroxylation, and dehydration. Condensation of a
      methyl acetoacetate equivalent followed by cyclization installed a pyrone moiety.
      Introduction of a formyl or hydroxymethyl unit into the pyrone ring via Pummerer
      related reactions furnished solanapyrones D (1) and E (2).

PMID- 12182632
TI  - trans-2,2'-Bi(1-phenyladamantylidene): the most twisted biadamantylidene.
AB  - The Grignard coupling of 2,2-dibromo-1-phenyladamantane gave trans-2,2'-bi(1
      phenyladamantylidene) (1-Ph). Single-crystal X-ray analysis indicated that 1-Ph
      has a 23.2 degrees twisted double bond, which is much more distorted than that of
      parent 2,2'-biadamantylidene (1-H) and that of the ethyl-substituted derivative
      (1-Et). A cyclic voltammogram showed a reversible electron oxidation wave at 0.87
      V vs Fc/Fc(+), which is 0.19 V lower than 1-H, indicating a significant increase
      in the HOMO energy level due to the distortion. The reaction of 1-Ph with 0.9
      equiv of bromine gave an intramolecular Friedel-Crafts alkylation product, while
      bromination of 1-H and 1-Me has been reported to give a bridged bromonium ion and
      a rearranged product, 2-(1-methyl-2-adamantylidene)-4
      bromotricyclo[5,3,1,0(3.9)]undec-4-ene, respectively.

PMID- 12182633
TI  - Extent of cyclic pi-electron delocalization modification in exocyclically
      substituted fulvenes.
AB  - Fulvene derivatives, 20 mono- and 14 di-exocyclically substituted, were optimized
      at the B3LYP/6-311+G level of theory. Aromaticity indices include aromatic
      stabilization energy (ASE), Schleyer's Nucleus Independent Chemical Shift (NICS),
      (3)He chemical shifts, anisotropy and exaltation of magnetic susceptibility, and
      the Harmonic Oscillator Model of Aromaticity (HOMA), which is a geometry-based
      descriptor. These indices were used to estimate the extent of a cyclic pi
      electron delocalization due to the substituent effect. A dramatic variation of
      these indices was found, indicating great sensitivity of the pi-electron
      structure of the ring. Except for anisotropy of magnetic susceptibility, all
      other indices exhibited perfect equivalence.

PMID- 12182634
TI  - Asymmetric synthesis of 1,2,3-trisubstituted cyclopentanes and cyclohexanes as
      key components of substance p antagonists.
AB  - An efficient asymmetric synthesis of 1,2,3-trisubstituted cyclopentanes and
      cyclohexanes is described. Three methods were developed for the preparation of
      the 2,3-disubstituted cyclopentenones and cyclohexenones, which are key achiral
      building blocks. These intermediates are reduced catalytically with (R)-2
      methyloxazaborolidine in high yield (82-98%) and excellent ee (89-96%). Directed
      reduction of the chiral allylic alcohols using Red-Al gives exclusively the 1,2
      anti stereochemistry (>99:1). Epimerization of the ester center followed by
      saponification/crystallization affords the desired hydroxyacids in good yield (65
      70%) and in high enantiomeric excess (>99%).

PMID- 12182635
TI  - Novel intramolecular [4 + 1] and [4 + 2] annulation reactions employing cascade
      radical cyclizations.
AB  - Tributyltin hydride and tris(trimethylsilyl)silane promote sequential/cascade
      free radical cyclization reactions of dienoate tethered vinyliodides or alkynes.
      These processes produce [4 + 1] and [4 + 2] annulated products. In contrast, the
      electrochemical reductions of the vinyliodides afford monocyclic compounds. Both
      the regiochemical and stereochemical courses of the sequential radical
      cyclizations strongly depend on substrate structure. Especially important is the
      balance between steric and stereoelectronic (Baldwin's rules) factors that serve
      to control cyclization regiochemistry.

PMID- 12182636
TI  - General protocols for the synthesis of C(2)-symmetric and asymmetric 2,8
      disubstituted analogues of Troger's base via efficient bromine-lithium exchanges
      of 2,8-dibromo-6H,12H-5,11-methanodibenzo[b,f][1,5]diazocine.
AB  - Methods for facile synthesis of symmetric and unsymmetric functionalized
      analogues of Troger's base were developed with use of 2,8-dibromo-6H,12H-5,11
      methanodibenzo[b,f][1,5]diazocine (2) as the starting material. C(2)-symmetric
      2,8-disubstituted analogues of Troger's base (4a-f) were synthesized via double
      bromine-lithium exchange of 2 followed by quench with electrophiles.
      Desymmetrization via single bromine-lithium exchange of 2, followed by quench
      with electrophiles, afforded asymmetric analogues of Troger's base (6a-g).
      Further reaction of 2-bromo-8-(trimethylsilyl)-6H,12H-5,11
      methanodibenzo[b,f][1,5]diazocine (6b) produced 7a-c via single bromine-lithium
      exchange and subsequent quench with electrophiles.

PMID- 12182637
TI  - Dinitro and quinodimethane derivatives of terthiophene that can be both oxidized
      and reduced. Crystal structures, spectra, and a method for analyzing quinoid
      contributions to structure.
AB  - Two new oligothiophenes, the dinitro compound 3',4'-dibutyl-5,5' '-dinitro
      2,2':5',2' '-terthiophene (1) and the quinodimethane 3',4'-dibutyl-5,5' '
      bis(dicyanomethylene)-5,5' '-dihydro-2,2':5',2' '-terthiophene (2), have been
      synthesized and studied with electrochemistry, UV-vis-NIR-IR spectroscopy, ESR,
      and X-ray crystallography. These compounds, designed to be both electron and hole
      carriers, show redox properties that are unusual for oligothiophenes. Cyclic
      voltammetry and spectroelectrochemistry demonstrated that each compound could be
      oxidized to a cation radical and reduced to an anion radical and dianion. The
      spectra of 2 and its three redox partners were analyzed in terms of a limiting
      structure in which the neutral 2 has orbitals corresponding to those of a
      substituted-terthiophene dication. Compound 1 crystallizes with the thiophene
      rings held in an unusual nonplanar, cisoid configuration in face-to-face pi
      stacks, with a spacing between molecules of 3.65 A. The C-C bond lengths of the
      outer nitro-substituted rings have quinoid character. Compound 2 crystallizes
      with the thiophene rings in a planar, transoid configuration. The molecules are
      held in pi-stacks formed from pi-dimers with a spacing between molecules of 3.47
      and 3.63 A. The C-C bond distances of the thiophene rings of 1 and 2 and other
      oligomers were analyzed by a principal component analysis. The analysis found
      that 93% of the structural variance resided in one principal component related to
      the quinoid structure of the oligothiophene moiety. The analysis reliably
      demonstrated a quinoid contribution to the structure of 1. This method should be
      applicable to understanding the structure of other conjugated molecules in which
      quinoid structures contribute.

PMID- 12182638
TI  - [1,5] Sigmatropic hydrogen shifts in cyclic 1,3-dienes.
AB  - Density functional calculations have been carried out for [1,5] hydrogen shifts
      in 1,3-cycloalkadienes (cyclohexadiene, cycloheptadiene, and cyclooctadiene). The
      complexity of the potential surfaces of these reactions was found to increase
      with ring size. For 1,3-cyclohexadiene a single transition structure for the
      [1,5] hydrogen shift was located, which connects the two enantiomeric conformers.
      For 1,3-cycloheptadiene two enantiomeric transition structures for the [1,5]
      hydrogen shift were located, which interconnect three conformers of the diene, a
      pair of enantiomeric conformers and a third achiral conformer. Finally for 1,3
      cyclooctadiene two diastereomeric transition structures were found in addition to
      six conformers (three pairs of enantiomeric conformers) of the diene. Calculated
      activation energies for the [1,5] hydrogen shifts were found to be in qualitative
      agreement with experiment. Variation in these energies are attributed to strain
      energies present in either the diene or the transition structure.

PMID- 12182639
TI  - Total synthesis and absolute configuration of liverwort diterpenes, (-)
      13(15)E,16E-3beta,4beta-epoxy-18-hydroxysphenoloba-13(15),16-diene and (-)
      13(15)Z,16E-3beta,4beta-Epoxy-18-hydroxysphenoloba-13(15),16-diene, by use of the
      ring closing metathesis reaction applied to seven-membered carbocycles with a
      trisubstituted double bond.
AB  - Seven-membered cyclic compounds possessing trisubstituted double bonds have been
      effectively constructed employing the Grubbs catalyst to effect olefin
      metathesis. The keto ester does not undergo cyclization; however, alcohols
      protected by the silyl groups smoothly cyclized into seven-membered compounds.
      The product was successfully converted to (-)-13(15)E,16E-3beta,4beta-epoxy-18
      hydroxysphenoloba-13(15),16-diene and (-)-13(15)Z,16E-3beta,4beta-epoxy-18
      hydroxysphenoloba-13(15),16-diene, liverwort diterpenes isolated from
      Anastrophyllum auritum to establish the absolute configuration.

PMID- 12182641
TI  - Lewis acid-promoted Kharasch-Curran additions: a competition kinetics study of
      bromine atom transfer addition of N-alpha-bromoacetyl-oxazolidinone to 1-hexene.
AB  - Lewis acids can efficiently promote free radical atom transfer reactions of an
      oxazolidinone imide substrate, 1, derived from alpha-bromo acetic acid. Thus, 1
      undergoes a radical chain addition to 1-hexene giving the atom transfer addition
      compound, 6, in the presence of scandium or ytterbium triflate in 1,2
      dichloroethane or a cosolvent mixture of 1/9 THF/dichloromethane. In 1,2
      dichloroethane the solution is heterogeneous, while the cosolvent mixture gives a
      homogeneous solution, even at temperatures of -78 degrees C. Competition
      experiments were carried out in both solvent systems with added carbon
      tetrachloride to study how Lewis acid affected the product distribution. In the
      presence of carbon tetrachloride, chloride 7 is formed in addition to 6 and the
      ratio of these two products depends on the amount of Lewis acid present. In the
      presence of ytterbium triflate, in the cosolvent system, the reaction rate of
      bromine atom transfer was enhanced up to 400-fold compared to the reaction
      without added Lewis acid. Significant rate enhancements were also obtained in the
      solvent 1,2-dichloroethane, although the analysis of the system is complicated by
      the heterogeneous nature of the medium. Computation of C-Br bond dissociation
      energies (BDE) of the complexed and uncomplexed oxazolidinone bromide suggest
      that complexation lowers the BDE due to the effect of the strong electron
      withdrawing group on the C-Br bond dipole.

PMID- 12182640
TI  - Photochemistry of N-isopropoxy-substituted 2(1H)-pyridone and 4-p-tolylthiazole
      2(3H)-thione: alkoxyl-radical release (spin-trapping, EPR, and transient
      spectroscopy) and its significance in the photooxidative induction of DNA strand
      breaks.
AB  - UVA-irradiation of the photo-Fenton reagents N-isopropoxypyridone 2b and N
      isopropoxythiazole-2(3H)-thione 3b releases radicals which induce strand breaks.
      Transient spectroscopy establishes N-O bond scission [Phi(N)(-)(O) = (75 +/- 8)%
      for 2b and (65 +/- 7)% 3b] as the dominating primary photochemical process to
      afford the DNA-damaging radicals. Product studies and laser-flash experiments
      reveal that the thiazolethione 3b leads primarily to the disulfide 5, from which
      through C-S bond breakage, the bithiazyl 6, the thiazole 7, and the
      isothiocyanate 8 are derived. Upon irradiation of pyridone 2b (300 nm) in aqueous
      media, a mixture of isopropoxyl and 2-hydroxyprop-2-yl radicals is formed, as
      confirmed by trapping with 5,5-dimethyl-1-pyrroline N-oxide (DMPO) and EPR
      spectroscopy. In contrast, the photolysis of the thiazolethione 3b (350 nm)
      affords exclusively the DMPO adducts of the isopropoxyl radicals. Control
      experiments disclose that the thiazolethione-derived photoproduct disulfide 5, or
      the intermediary thiyl radicals B, scavenge the carbon-centered 2-hydroxyprop-2
      yl radicals, which are generated from the isopropoxyl radicals by hydrogen shift.
      With supercoiled pBR 322 DNA in a 60:40 mixture of H(2)O-MeCN, the pyridone 2b
      and the thiazolethione 3b display moderate strand-break activity (17% open
      circular DNA for 2b and 12% for 3b). In pure water, however, the pyridone 2b
      photoinduces substantially more DNA cleavage (32% open-circular DNA), which is
      attributed to the peroxyl radicals generated from the 2-hydroxyprop-2-yl radicals
      by oxygen trapping. The lower strand-break activity of the thiazolethione 3b
      derives presumably from isopropoxyl radicals, because only these are detected in
      the photolysis of this photo-Fenton reagent.

PMID- 12182642
TI  - Prochirality revisited. An approach for restructuring stereochemistry by novel
      terminology.
AB  - The importance of orbits (equivalence classes) has been stressed to restructure
      stereochemistry. The concept of sphericity has been formulated by a new scheme
      that requires a minimum set of knowledge on point-group theory. The concept of
      prochirality has been revisited from the viewpoint based on the new formulation
      of sphericity. A variety of objects such as atoms, ligands, and faces are
      discussed as the members of such an orbit. In particular, orbits for atoms in
      tetrahedral molecules and for the faces of carbonyl compounds, ethylene
      derivatives, and allene derivatives have been examined in terms of the concept of
      sphericity. The conventional topicity terms of two categories ("topic
      relationship between two sites" and "topic attribute of a site") have been
      effectively replaced by the sphericity terms.

PMID- 12182643
TI  - 1,2-Oxopalladation versus pi-allyl palladium route. A regioconvergent approach to
      a key intermediate for cyclopentanoids synthesis. New insights into the Pd(II)
      catalyzed lactonization reaction.
AB  - Regioconvergent synthesis of the key lactone 1 from an equimolar mixture of the
      two olefins 4 and 5 was achieved by unique Pd(II) chemistry. The synthetic
      versatility of lactone 1 has been demonstrated in the synthesis of iridoids and
      of the endo-Corey lactone 2, which is a key intermediate for the F(2)-isoprostane
      synthesis. Upon exposure of the sodium salts of 4 and 5 to a catalytic amount of
      Pd(OAc)(2) under oxygen, in the presence of AcOH, an isomeric lactone 12 was
      obtained in addition to the title compound 1. The Pd(II) lactonization was
      optimized by fine-tuning all the factors participating in the catalytic cycle:
      solvent, oxidant, co-oxidant, and Pd(II) source. The Hosokawa's heterobimetallic
      couple emerged as the catalyst of choice. With a Cu(II)-Pd(II) couple, the redox
      process was transferred to copper, and the formal oxidation state of palladium
      remained constant during the reaction. By virtue of this new methodology, lactone
      1 was obtained in a rewarding 60% yield, along with isomeric lactone 12 in 30%
      yield. A detailed mechanistic study was carried out in order to elucidate the
      formation of lactones 1 and 12. Lactone 1 was formed from either olefin 8 or
      olefin 10; on the other hand, lactone 12 was formed exclusively from olefin 10.
      An intramolecular 1,2-acyloxypalladiation was invoked for the transformation of 8
      into 1, whereas the pi-allyl complexes 13 and 11 were involved in the
      transformation of olefin 10 into 12 and 1, respectively.

PMID- 12182644
TI  - Theoretical study of the photochemical [2 + 2]-cycloadditions of cyclic and
      acyclic alpha,beta-unsaturated carbonyl compounds to ethylene.
AB  - The ground and first triplet excited-state potential energy surfaces of the [2 +
      2]-cycloadditions of 2-cyclohexenone, methyl acrylate, and methyl crotonate to
      ethylene have been studied by means of CASSCF and DFT-B3LYP calculations. The
      attack of ethylene to the (3)(pi-pi) alpha,beta-unsaturated carbonyl compound
      leads to the formation of a triplet 1,4-biradical intermediate that evolves to
      the ground-state potential energy surface. The outcome of the reaction is
      governed by the competition between the deactivation of the (3)(pi-pi) alpha,beta
      unsaturated carbonyl compound itself and its reaction with ethylene to form the
      triplet 1,4-biradical. For 2-cyclohexenone, the potential energy barrier
      corresponding to the formation of the biradical intermediate is lower than for
      the acyclic systems. On the other hand, the energy necessary to reach the
      crossing point between the (3)(pi-pi) and the ground-state potential energy
      surfaces is lower for the acyclic systems than for 2-cyclohexenone. For methyl
      acrylate and methyl crotonate, the decay of the (3)(pi-pi) state of the isolated
      molecule is therefore expected to be faster than the formation of the 1,4
      biradical, so that the [2 + 2]-cycloaddition will not take place. However, for 2
      cyclohexenone the formation of the triplet 1,4-biradical is favorable, and the
      process will lead to the formation of the corresponding cyclobutane derivative.

PMID- 12182645
TI  - Stereodivergent process for the synthesis of the decahydroquinoline type of
      dendrobatid alkaloids.
AB  - A flexible and stereodivergent synthesis of the cis- and trans-fused 2,5
      disubstituted octahydroquinolinone ring systems bearing all four stereogenic
      centers for the synthesis of the decahydroquinoline type of dendrobatid alkaloids
      has been achieved. The strategy involves stereoselective and stereodivergent
      construction of 2,3,6-trisubstituted piperidine ring systems using the Michael
      type of conjugate addition reaction to the enaminoesters 1 and 3, the
      intramolecular aldol type of cyclization reaction of keto aldehydes 11 and 12,
      and ring-closing metathesis of 21 as key steps.

PMID- 12182646
TI  - 1,2-silyl-migrative cyclization of vinylsilanes bearing a hydroxy group:
      stereoselective synthesis of multisubstituted tetrahydropyrans and
      tetrahydrofurans(1).
AB  - Acid-catalyzed intramolecular addition of a hydroxy group to alpha-alkylated
      vinylsilanes has been studied. Treatment of (Z)-5-alkyl-5-silyl-4-penten-1-ols 1
      (R = alkyl) with 5 mol % TiCl(4) in CHCl(3) gave trans-2-alkyl-3
      silyltetrahydropyrans 2 exclusively (trans/cis = >99/1 to 97/3). The cyclization
      efficiency and rate strongly depended on the geometry of the C-C double bond and
      the silyl group. The use of (E)-vinylsilanes resulted in lower yields with poor
      cis-selectivity. In the cyclization of (Z)-1 (R = Bu), the silyl group used, the
      reaction time, and the yield of 2 were as follows: SiMe(2)Ph, 9.5 h, 75%;
      SiMe(3), 7.5 h, 66%; SiMePh(2), 24 h, 58%; SiMe(2)-t-Bu, 0.75 h, 85%; SiMe(2)Bn,
      1.5 h, 78%. This 1,2-silyl-migrative cyclization could be applied to
      stereoselective synthesis of trisubstituted tetrahydropyrans. The acid-catalyzed
      reaction of 1-, 2-, or 3-substituted (Z)-5-silyl-4-nonen-1-ols 8 gave r-2,t-3,c-6
      , r-2,t-3,t-5-, or r-2,t-3,c-4-trisubstituted tetrahydropyrans with high
      diastereoselectivity, respectively. (Z)-4-Alkyl-4-silyl-3-buten-1-ols 5 as well
      as 1 underwent the 1,2-silyl-migrative cyclization to give 2-alkyl-3
      silyltetrahydrofurans 6 with high trans-selectivity. This silicon-directed
      cyclization was also available for the stereoselective synthesis of tri- and
      tetrasubstituted tetrahydrofurans.

PMID- 12182647
TI  - Dehydro[12]- and -[18]annulenes fused with tetrafluorobenzene: synthesis,
      electronic properties, packing structures, and reactivity in the solid state.
AB  - Dehydro[12]- and -[18]annulenes 3 and 4 fused with tetrafluorobenzene were newly
      synthesized by the copper-mediated oxidative coupling of 1,2
      diethynyltetrafluorobenzene. The UV-vis spectra of 3 and 4 showed the maximum
      absorption to be almost identical to that of the corresponding unsubstituted
      benzodehydro[12]- and -[18]annulenes 1 and 2, respectively, while the reduction
      waves in cyclic voltammetry observed at potentials of -1.48 and -1.56 V vs
      Fc/Fc(+) for 3 and 4 were less negative than those for 1 and 2. In agreement with
      these results, theoretical calculations (B3LYP/6-31G(d)) indicated that the HOMO
      LUMO gap is similar for 1 and 3 and for 2 and 4 but that the LUMO levels of 3 and
      4 are apparently lowered by the electronegative fluorine substituents. The X-ray
      crystallography of single crystals grown from 3 (crystal A), 3.C(6)H(6) (crystal
      B), and a mixture of 1 and 3 (crystal C) demonstrated that the molecules of 3 are
      stacked in a slanted manner in crystals A and B, while those of 1 and 3 form
      sandwichlike 1:2 complexes (3.1.3) that are stacked in a columnar arrangement in
      crystal C. Despite the suitable packing for topochemical polymerization, crystals
      A-C were quite stable against photochemical reaction. In contrast, differential
      scanning calorimetry showed that the thermal polymerization occurred explosively
      at 120-135 degrees C.

PMID- 12182648
TI  - Progress toward a peptidomimetic of laminin-derived pentapeptide YIGSR: synthesis
      of the unique tricyclic core structure.
AB  - The peptide sequence YIGSR, a segment of the basement membrane matrix
      glycoprotein laminin, has been identified as a key component in tumor cell
      invasion. Guided by extensive NMR work and de novo design algorithms, a
      nonpeptide mimetic of this pentapeptide was identified as a lead candidate for
      synthesis. The target displays the key amino acid side chains from a novel
      tricyclic scaffold. The first synthesis of this unique scaffold is completed in
      11 steps and 7% overall yield.

PMID- 12182650
TI  - Selectivity via cooperative interactions: detection of dicarboxylates in water by
      a pinwheel chemosensor.
AB  - The recognition properties of a cooperative pinwheel chemosensor for
      dicarboxylates are described. The sensor possesses four guanidinium recognition
      elements to cooperatively bind two dicarboxylates of varying size. The effect of
      cooperativity and the read-out mechanism contributes to favorable binding
      constants for dicarboxylates in water, as well as a high degree of selectivity
      over monocarboxylates. Appropriate methods of reporting affinity for cooperative
      systems are discussed.

PMID- 12182649
TI  - Efficient synthesis of 4-(2'-alkenyl)-2,5-dihydrofurans and 5,6-dihydro-2H-pyrans
      via the Pd-catalyzed cyclizative coupling reaction of 2,3- or 3,4-allenols with
      allylic halides.
AB  - In the absence of a base, palladium(II) catalysts, such as PdCl(2),
      PdCl(2)(CH(3)CN)(2), Pd(OAc)(2), and [(pi-C(3)H(5))PdCl](2), can catalyze the
      cyclizative coupling reaction of 2,3- or 3,4-allenols with allylic halides in DMA
      at room temperature to provide 2,5-dihydrofurans and 5,6-dihydro-2H-pyrans,
      respectively, in moderate to good yields. Under similar reaction conditions,
      nonsubstituted 2,3-allenol 1s affords bimolecular cyclizative coupling product 5s
      as the major product. The scope of the reaction and its mechanism have been
      studied briefly. On the basis of the experimental results, the transformation was
      believed to proceed via a divalent palladium-catalyzed pathway.

PMID- 12182651
TI  - Triplet energy distribution in photoinitiators containing two dissociable groups.
AB  - Suitable probe molecules containing the benzophenone chromophore and one
      dissociable bond [perester 1 or C-X (4, 5)] or two such bonds (2, 3) have been
      synthesized and studied to examine intramolecular triplet energy dispersion.
      Triplet energies and phosphorescence quantum yields as well as quantum
      efficiencies of bond scissions have been studied, and the flow of triplet energy
      in such molecules is discussed. Upon irradiation at 350 nm in either benzene or
      methanol, the target peresters undergo dissociation of both cleavable groups,
      producing a pair of radicals. The presence of a benzylic chloride function has
      little influence on the efficiency of perester dissociation. However, the
      presence of a benzylic bromide function was found to decrease the quantum yield
      of decomposition of the perester function of 3. This can be explained by taking
      into account the effect of the heavy atom and the rate of cage geminate radical
      pair recombination. The nature of the heavy atom perturbation, however, was found
      to be different in 5 as compared with 3.

PMID- 12182652
TI  - Nucleophilic addition of benzenethiol to 1',2'-unsaturated nucleosides: 1'-C
      phenylthio-2'-deoxynucleosides as anomeric radical precursors.
AB  - The addition reaction of benzenethiol to the glycal portion of 1',2'-unsaturated
      uridine proceeds efficiently in the presence of Et(3)N. The mechanism involves
      nucleophilic attack of thiolate at the anomeric position in the rate-determining
      step, wherein conjugation between the nucleobase and the glycal portion is
      crucial. The derivative having a methyl group either at the 2'- or 6-position did
      not undergo this addition reaction, due to their sterically prohibited
      coplanarity. The 1',2'-unsaturated derivatives of thymine and adenine can also be
      used as substrates for this addition reaction. It was also shown that the
      resulting 1'-C-phenylthio-2'-deoxynucleosides serve as precursors for radical
      mediated C-C bond formation at the anomeric position.

PMID- 12182653
TI  - Laser flash photolysis of [3,n]paracyclophan-2-ones. Direct observation and
      chemical behavior of 4,4'-(1,n-alkanediyl)bisbenzyl biradicals.
AB  - The 4,4'-(1,n-alkanediyl)bisbenzyl biradicals (2b-d) have been generated from the
      Norrish type-I reaction of [3,n]paracyclophan-2-ones (1b-d) giving the
      paracyclophanes 3b-d as the only reaction products. The behavior of biradicals 2b
      d has been studied in detail and compared with the previously reported biradical
      2a. The lifetimes increase as the chain length decreases and are affected by the
      solvent viscosity, thus showing the effect of the length of the chain on the
      conformations of the biradicals. Quenching with persistent radicals such as TEMPO
      resulted in length-dependent rate constants. Finally, the study of the magnetic
      field effects on the biradical lifetimes suggest that ISC control determines
      biradical lifetimes for long-chain systems.

PMID- 12182654
TI  - Functionalization of the methylene groups of p-tert-butylcalix[4]arene: S-C, N-C,
      and C-C bond formation.
AB  - Reaction of the calixarene derivative 7 with two exocyclic double bonds with
      carbon-, nitrogen-, oxygen-, or sulfur-containing nucleophiles afforded
      bis(spirodienone) derivatives substituted at two opposite methylene groups in a
      trans fashion. LiAlH(4) reduction of the bis(spirodienone) derivatives with two
      methylenes functionalized by thiomethoxy, diethyl malonate, or anilino
      substituents yielded trans methylene-substituted calix[4]arenes. Upon standing in
      solution, the calixarene derivative incorporating SMe groups on the bridges
      underwent trans right harpoon over left harpoon cis isomerization. An
      equilibration study performed on this calixarene derivative (tetrachloroethane
      d(2), 430 K) indicated that the cis isomer is the form of lower free energy.

PMID- 12182655
TI  - Advanced oxidation chemistry of paracetamol. UV/H(2)O(2)-induced
      hydroxylation/degradation pathways and (15)N-aided inventory of nitrogenous
      breakdown products.
AB  - The advanced oxidation chemistry of the antipyretic drug paracetamol (1) with the
      UV/H(2)O(2) system was investigated by an integrated methodology based on (15)N
      labeling and GC-MS, HPLC, and 2D (1)H, (13)C, and (15)N NMR analysis. Main
      degradation pathways derived from three hydroxylation steps, leading to 1,4
      hydroquinone/1,4-benzoquinone, 4-acetylaminocatechol and, to a much lesser
      extent, 4-acetylaminoresorcine. Oxidation of the primary aromatic intermediates,
      viz. 4-acetylaminocatechol, 1,4-hydroquinone, 1,4-benzoquinone, and 1,2,4
      benzenetriol, resulted in a series of nitrogenous and non-nitrogenous degradation
      products. The former included N-acetylglyoxylamide, acetylaminomalonic acid,
      acetylaminohydroxymalonic acid, acetylaminomaleic acid, diastereoisomeric 2
      acetylamino-3-hydroxybutanedioic acids, 2-acetylaminobutenedioic acid, 3
      acetylamino-4-hydroxy-2-pentenedioic acid, and 2,4-dihydroxy-3-acetylamino-2
      pentenedioic acid, as well as two muconic and hydroxymuconic acid derivatives.
      (15)N NMR spectra revealed the accumulation since the early stages of substantial
      amounts of acetamide and oxalic acid monoamide. These results provide the first
      insight into the advanced oxidation chemistry of a 4-aminophenol derivative by
      the UV/H(2)O(2) system, and highlight the investigative potential of integrated
      GC-MS/NMR methodologies based on (15)N-labeling to track degradation pathways of
      nitrogenous species.

PMID- 12182656
TI  - Regio- and stereoselective synthesis of (E)-alkene trans-Xaa-Pro dipeptide
      mimetics utilizing organocopper-mediated anti-S(N)2' reactions.
AB  - Proline dipeptides (Xaa-Pro) exist as an equilibrium mixture of cis- and trans
      rotamers, which depends on the energy barriers for imide isomerization. This
      conformation mixture contributes to both structure and function of proline
      containing peptides and proteins. Structural motifs resembling these cis- or
      trans-conformers have served as useful tools for elucidating contributions of
      proline residues in the physicochemical and biological profiles of structures
      which contain them. Among such motifs are alkene dipeptide isosteres which mimic
      cis- or trans-imide using (Z)- or (E)-alkene, respectively. In this report, the
      first regio- and stereoselective syntheses of (E)-alkene dipeptide isosteres (20,
      31, and 35) corresponding to trans-proline dipeptides are described. Key to the
      synthesis of these mimetics is the anti-S(N)2' reaction of vinyl aziridines such
      as 15 or vinyl oxazolidinones such as 28 and 32 with organocopper reagents "RCu"
      (R = CH(2)SiMe(2)(Oi-Pr)). Reaction of cis-vinylaziridine 15 derived from L
      serine with organocopper reagent gave a precursor of the trans-L-Ser-D-Pro type
      alkene isosteres 20, accompanied by an S(N)2 side product. One limitation with
      the use of such aziridine-mediated methodology is formation of the corresponding
      trans-aziridine 22, which leads to L-L type isosteres, that is unstable and
      obtainable only in low yield. On the other hand, both isomers of oxazolidinone
      derivatives can be easily obtained from N-Boc-protected amino alcohols. The
      reaction of trans- 28 or cis-oxazolidinone derivative 32 with organocopper
      reagents proceeds quantitatively with high regio- and diastereoselectivities in
      anti-S(N)2' fashion. Subsequent oxidative treatment of the newly introduced
      isopropoxydimethylsilylmethyl group yields trans-L-Ser-L-Pro 31 or trans-L-Ser-D
      Pro type isosteres 35, respectively. Of note, synthesized isostere 31 can also be
      converted to trans-phosphoSer-Pro 42 and trans-Cys-Pro mimetics 44. The present
      synthetic methodology affords trans-Xaa-Pro alkene-type dipeptide isosteres in
      high yield with relatively simple manipulation.

PMID- 12182657
TI  - Diastereoselective synthesis of new psi[(E)-CH=CMe]- and psi[(Z)-CH=CMe]-type
      alkene dipeptide isosteres by organocopper reagents and application to
      conformationally restricted cyclic RGD peptidomimetics.
AB  - Diastereoselective synthesis of new psi[(E)-CH=CMe]- and psi[(Z)-CH=CMe]-type
      alkene dipeptide isosteres corresponding to dipeptides having one N-methylamino
      acid, and application to bioactive peptides, are described. In a key reaction
      introducing the chiral alpha-alkyl group of the isosteres, organocopper-mediated
      alkylation of syn-beta-methylated gamma-mesyloxy-alpha,beta-enoate 26a afforded E
      and Z-isomers of anti-S(N)2' products in a solvent-dependent manner. The
      resulting two isosteres, D-Phe-psi[(E)-CH=CMe]-L-Val 27a and D-Phe-psi[(Z)
      CH=CMe]-L-Val 28b, which corresponded to trans- and cis-conformers of D-Phe-L
      MeVal, respectively, were utilized in a structure-activity relationship study on
      cyclic RGD peptides 1 and 2, in company with a psi[(E)-CH=CH]-type alkene
      dipeptide isostere, D-Phe-psi[(E)-CH=CH]-L-Val. The cyclic isostere-containing
      pseudopeptides 3, 4, and 40 were synthesized and biological activity against
      integrin alpha(V)beta(3) and alpha(IIb)beta(3) receptors were also evaluated.

PMID- 12182658
TI  - Diastereoselective and intramolecular cycloadditions of asymmetric p-nitroso
      phosphine oxides.
AB  - Benzyl phenyl P-nitroso phosphine oxide (5) reacts as an N-O heterodienophile
      with 1,3-cyclopentadiene to give the diastereomeric cycloadducts 6a,b in a ratio
      of 1.5:1 (6a:6b). The same reaction in the presence of tin tetrachloride produces
      6a,b in a ratio of 2.9:1 (6a:6b). Cycloaddition of the structurally modified P
      nitroso phosphine oxide (18) with 1,3-cyclopentadiene forms the diastereomeric
      cycloadducts 16a,b in a ratio of 3.1:1 (16a:16b). These results suggest the
      reactions of these P-nitroso phosphine oxides and 1,3-cyclopentadiene occur
      through a transition state where the heterodienophile adopts an s-cis
      conformation and approaches the diene in an exo fashion syn to the phenyl group.
      This model resembles those proposed for the cycloadditions of the structurally
      similar asymmetric vinyl phosphine oxides. Reaction of 18 with 1,3
      cyclopentadiene in the presence of a Lewis acid produces cycloadducts 16a,b in a
      ratio of 7:1 (16a:16b), which approaches synthetic utility. Similar experiments
      show that 1,3-cyclohexadiene likely reacts with P-nitroso phosphine oxides
      through a different transition state, limiting current predictions regarding the
      diastereoselectivity of these reactions. The intramolecular cycloaddition of an
      asymmetric P-nitroso phosphine oxide (19) for the first time produces a unique
      phosphorus-containing heterocyclic compound (20).

PMID- 12182659
TI  - Synthesis of the ABC ring system of manzamine A.
AB  - A synthesis of the core ABC ring system of the manzamine alkaloids is described,
      starting from arecoline. The key steps involve a Claisen rearrangement to set up
      a 4-substituted-3-methylenepiperidine and a stereoselective azomethine ylide
      dipolar cycloaddition reaction. Condensation of the aldehyde 6 and sarcosine
      ethyl ester hydrochloride salt gives an intermediate azomethine ylide, which
      undergoes an intramolecular cycloaddition reaction to set up two new rings and
      three new chiral centers stereoselectively. The aldehyde 6 was not a suitable
      substrate for related azomethine ylide cycloaddition reactions with other amines.
      However, the related dimethyl acetal 26 could be condensed with a variety of
      amines to give the desired tricyclic products. The cycloaddition reaction with N
      methyl or N-allyl glycine ethyl ester gave almost exclusively the exo adduct,
      whereas cycloaddition with glycine ethyl ester gave the endo adduct.

PMID- 12182660
TI  - Anion effects on the recognition of ion pairs by calix[4]arene-based
      heteroditopic receptors.
AB  - A novel heteroditopic receptor (5) based on a rigid calix[4]arene cavity bearing
      at the upper rim four arylsulfonamido binding sites has been synthesized. The
      binding abilities of this new host have been investigated in apolar solvents
      toward a series of tetramethylammonium salts (tosylate, chloride, acetate,
      trifluoroacetate, and picrate) and compared with those of monotopic and
      heteroditopic calix[4]arene-bis(crown-3)-based receptors 1 and 2 in order to
      evaluate the role of the anion on ion-pair recognition. While monotopic host 1
      shows an efficiency order toward the different salts that increases when the
      anion is less interactive (Hofmeister trend), an opposite role of the
      counteranion on the recognition process was observed with host 5 (anti-Hofmeister
      trend). A more complex behavior is experienced by host 2, which shows a high and
      leveled efficiency for all the anions tested. The results obtained were explained
      on the basis of the different types of ion pairs present in the recognition
      process. Further information on the role of the anion were obtained by the "dual
      host" strategy utilizing the tri-n-butylthioureido derivative of tren 7, which
      forms a stable complex with chloride anion. The very high efficiency shown by
      these heteroditopic hosts opens new routes in supramolecular projects and is a
      very interesting tool in the molecular recognition of ion-pairs and its
      applications.

PMID- 12182661
TI  - Development of an effective chiral auxiliary for hydroxyalkyl radicals.
AB  - The development of an effective chiral auxiliary for hydroxyalkyl radicals is
      delineated. Both the 2-tetrahydropyranyl (THP) and tri-O-benzyl-2-deoxy-alpha-D
      glucopyranosyl (GLU) auxiliaries resulted in diastereoselective radical additions
      to methyl acrylate at -78 degrees C (ds = 6/1 and 11/1, respectively). The
      developing stereochemistry at the radical center was completely under auxiliary
      control. Correlation experiments showed that the D-GLU auxiliary led to attack on
      the radical Si-face. The selectivity of these radical additions dropped-off
      considerably when the more reactive 2-nitropropene trap was employed.
      Computational studies suggested that the observed facial selectivity was due
      primarily to entropic factors in the transition state but that a smaller
      temperature-dependent enthalpic contribution was also involved. It was
      hypothesized that incorporation of a quaternary center at C-6 (THP numbering)
      would restore the facial selectivity with more reactive radical traps by
      restricting the orientations available to the incoming alkene. In the event, the
      trans-6-tert-butyltetrahydropyranyl (tBu-THP) auxiliary resulted in very good
      diastereoselection with 2-nitropropene (ds = 35/1 at -78 degrees C, 15/1 at 0
      degrees C, and 8/1 at RT) as did the tri-O-benzyl-6,6-dimethyl-2-alpha-D
      deoxyglucopyranosyl (diMe-GLU) auxiliary during additions to ethyl alpha
      trifluoroacetoxyacrylate (ds = 10/1 at 0 degrees C). A protocol for recovery of
      the sugar-derived chiral auxiliaries was also established. This work sets the
      stage for the development of a novel approach to 1, 3, 5.(2n + 1) polyols based
      on iterative radical homologation as well as the application of these pyranosidic
      auxiliaries to other synthetically important reactions.

PMID- 12182662
TI  - Theory supplemented by experiment. Electronic effects on the rotational stability
      of the amide group in p-substituted acetanilides.
AB  - The electronic effect of polar substituents on the barrier of internal rotation
      around the amide carbon-nitrogen bond in a series of 10 p-substituted
      acetanilides is studied by applying density functional theory at the B3LYP/6
      31G(d,p) level. The theoretical results are supplemented by experimental data on
      the amide C=O and N-H stretching mode frequency shifts. It is shown that
      computations at the theoretical level employed provide a valuable approach in
      studying the factors determining the conformational stability of the studied
      series of compounds. It is found that an excellent linear dependence between the
      barriers of rotation and frequency shifts exists. It is concluded that the
      variations of the amide C=O stretching mode frequency can be used for
      quantitative characterization of the amide group conformational flexibility in
      the studied series of acetanilides.

PMID- 12182663
TI  - Synthesis of suspected carcinogenic metabolites of 7H-benzo[c]fluorene, a coal
      tar component implicated in causation of lung tumors.
AB  - High incidences of lung tumors were observed in mice fed coal tar in their diet.
      The principal component of tar that gives rise to DNA-bound adducts in mouse lung
      was identified as 7H-benzo[c]fluorene (BcF). We now report the synthesis of
      suspected active metabolites of BcF, specifically the trans-3,4-dihydrodiol of
      BcF (2), its likely proximate carcinogenic metabolite, and the corresponding anti
      and syn-diol epoxides of BcF (3 and 4) in which the epoxide ring resides in the
      pseudobay region. The diol epoxide derivatives (3 and 4) are postulated to be
      ultimate carcinogenic metabolites of BcF that bind to DNA in mouse lung.

PMID- 12182664
TI  - Sulfur-rich heterocycles from 2-metalated benzo[b]thiophene and benzo[b]furan:
      synthesis and structure.
AB  - The reaction of 2-lithiated benzo[b]thiophene with 8 equiv of elemental sulfur
      was found to give pentathiepino[6,7-b]benzo[d]thiophene. In contrast, treatment
      of 2-lithiated benzo[b]furan with sulfur under similar conditions produced the
      interesting ring system bis(benzo[4,5]furo)[2,3-e:3',2'-g][1,2,3,4]tetrathiocine.
      Both of these new cyclic polysulfides were studied by X-ray crystallography. Two
      polymorphic forms of pentathiepino[6,7-b]benzo[d]thiophene were found, displaying
      similar conformations but different packing schemes, which was also evident from
      powder diffraction data.

PMID- 12182665
TI  - Hydroformylation of alkenes employing rhodium(i) complexes and a phosphine oxide
      ligand.
AB  - Following the facile synthesis of a novel phosphine oxide compound,
      (diphenylphosphinoyl)phenylmethanol (1), this compound was employed as a ligand
      in the rhodium-catalyzed hydroformylation of alkenes, with good conversions and
      regioselectivities. This ligand was partially resolved using an enzyme, and
      enantioselective hydroformylation was carried out with the addition of a
      rhodium(I) complex. The rhodium(I) complex containing ligand 1 was not isolated,
      although it was subjected to low-temperature NMR studies.

PMID- 12182666
TI  - An effective procedure for the acylation of azaindoles at C-3.
AB  - Conditions for attachment of acetyl chloride, benzoyl chloride, and chloromethyl
      oxalate to the 3-position of 4-, 5-, 6-, or 7-azaindoles were explored. Best
      results were achieved with an excess of AlCl(3) in CH(2)Cl(2) followed by the
      addition of an acyl chloride at room temperature.

PMID- 12182667
TI  - Practical synthesis of chiral emopamil left hand as a bioactive motif.
AB  - An asymmetric synthesis of (2S)-2-(2-isopropyl)-5-hydroxy-2-phenylpentanenitrile
      (emopamil left hand, 2) has been completed by use of the MAD (methyl aluminum
      bis(4-methyl-2,6-di-tert-butylphenoxide)-induced rearrangement of a chiral
      epoxyalcohol as the key reaction. The stereochemistry of the chiral quaternary
      center was confirmed by transformation of 2 to (S)-noremopamil. This method
      requires minimal purification procedures and affords high chemical and optical
      yields. Acid-catalyzed isomerization of an allylaldehyde and retro-aldol type
      racemization at the quaternary carbon of a nitrile-alcohol were encountered.

PMID- 12182668
TI  - Dimethylformamide as a carbon monoxide source in fast palladium-catalyzed
      aminocarbonylations of aryl bromides.
AB  - Dimethylformamide (DMF) acts as an efficient source of carbon monoxide and
      dimethylamine in the palladium-catalyzed aminocarbonylation (Heck carbonylation)
      of p-tolyl bromide to provide the dimethylamide. Addition of amines to the
      reaction mixture in excess delivers the corresponding aryl amides in good yields.
      The amines employed, benzylamine, morpholine, and aniline, all constitute good
      reaction partners. The reaction proceeds smoothly with bromobenzene and more
      electron-rich aryl bromides, but electron-deficient aryl bromides fail to undergo
      aminocarbonylation. The reactions are conducted at 180-190 degrees C for 15-20
      min with microwave heating in a reaction mixture containing imidazole and
      potassium tert-butoxide: the latter is required to promote decomposition of the
      DMF solvent at a suitable rate. The beneficial effects of controlled microwave
      irradiation as an energy source for the rapid heating of the carbonylation
      reaction mixture are demonstrated. The carbonylation procedure reported herein,
      which relies on the in situ generation of carbon monoxide, serves as a convenient
      alternative to other carbonylation methods and is particularly applicable to
      small-scale reactions where short reaction times are desired and the direct use
      of carbon monoxide gas is impractical.

PMID- 12182669
TI  - Comparison of electrophilic amination reagents for N-amination of 2
      oxazolidinones and application to synthesis of chiral hydrazones.
AB  - Comparison of several hydroxylamine-based electrophilic ammonia equivalents in
      the N-amination of 2-oxazolidinones revealed that O-(p-nitrobenzoyl)hydroxylamine
      (NbzONH(2)) and sodium hydride in dioxane is a superior reagent combination for
      this purpose. Practical preparations of a variety of chiral N-acylhydrazones by
      this method gave yields ranging from 45 to 95%. Methods for exchange or removal
      of the aldehyde component have been developed, making this a general route to
      chiral N-acylhydrazones of interest for asymmetric synthesis applications.

PMID- 12182670
TI  - Synthesis of the pro-gly dipeptide alkene isostere using olefin cross-metathesis.
AB  - An approach to the synthesis of dipeptide olefin isosteres using intermolecular
      olefin cross-metathesis is presented. In particular, a synthesis of the Pro-Gly
      isostere (1) is reported. Conversion of N-BOC-proline into the corresponding
      vinyl-substituted carbamate provides the N-terminal cross-metathesis partner (2).
      Methyl 3-butenoate (3) is employed as the C-terminal component. Treatment of the
      two partners in an optimized molar ratio affords the cross product 1 (83% yield).
      Three other examples are demonstrated to evaluate the potential of the approach.

PMID- 12182671
TI  - High-speed heck reactions in ionic liquid with controlled microwave heating.
AB  - Palladium-catalyzed Heck arylations in the polar and robust ionic liquid, 1-butyl
      3-methylimidazolium hexafluorophosphate (bmimPF(6)), have for the first time been
      accomplished under microwave irradiation. The couplings were efficiently
      performed in sealed tubes within 5-45 min of heating. Without significant
      reductions in yield, a phosphine-free ionic catalyst phase could be recycled in
      five successive 20 min reactions at 180 degrees C. The product was easily removed
      from the reaction medium by distillation.

PMID- 12182672
TI  - Convenient preparation of indolyl Malonates via Carbenoid insertion.
AB  - Indoles, when treated with methyldiazomalonate under catalysis by
      rhodium(II)acetate, undergo C-H and N-H insertion reactions regioselectively
      depending on the substitution pattern on the indole moiety. In indoles where the
      3-position is unsubstituted, high yields of the C3-H insertion product were
      observed. In 3-alkylindoles, 2-substitution predominated, while N
      methyltetrahydrocarbazole yielded the product resulting from insertion into the
      C6-H bond. Indoles in which the nitrogen is unprotected yield varying degrees of
      N-H insertion.

PMID- 12182673
TI  - Synthesis of functionalized 1,5-cyclooctadienes by LICKOR metalation.
AB  - 1,5-Cyclooctadiene was lithiated under LICKOR superbase conditions followed by
      reaction with alkyl halides or ethylene oxide to yield 3-substituted 1,5
      cyclooctadienes in high yield and purity. This procedure is suitable for
      preparation of 1,5-cyclooctadienes carrying pendant functional groups for
      immobilization on solid-phase resins.

PMID- 12182674
TI  - Competing ring-photoisomerization pathways in the 1,2,4-oxadiazole series. An
      unprecedented ring-degenerate photoisomerization.
AB  - The irradiation of some 5-alkyl-3-amino-1,2,4-oxadiazoles at lambda = 254 nm in
      methanol in the presence of triethylamine (TEA) gave ring-photoisomerization both
      into 2-alkyl-5-amino-1,3,4-oxadiazoles and, unprecedently, into the ring
      degenerate 3-alkyl-5-amino-1,2,4-oxadiazoles. The competing ring contraction-ring
      expansion route and the internal cyclization-isomerization mechanism explain the
      results.

PMID- 12182675
TI  - Catalytic asymmetric synthesis of protected tryptophan regioisomers.
AB  - Tryptophan 1 (Trp) is superior to all other naturally occurring peptide residues
      in its ability to bind cations (the cation-pi interaction). In an effort to
      expand the toolbox of Trp-like amino acids, in this note we report catalytic
      asymmetric syntheses of Trp regioisomers 2a-e, where the alanine unit is attached
      not to C-3 of indole but to C-2, C-4, C-5, C-6, or C-7. Excellent asymmetric
      induction is obtained in each case (generally >97% ee). Ab initio calculations
      suggest that the indole nuclei of 2a-e will bind Na(+) with the same affinity as
      that of Trp.

PMID- 12182676
TI  - Synthesis of cyclic peptidomimetics from aldol building blocks.
AB  - Aldol products (3-hydroxy acids) with an allyl-protected hydroxy group were
      converted to amino alcohols by Curtius rearrangement. Combination of the
      carboxylic acid with the amino alcohols gave the amides 10. Ring-closing
      metathesis led to the 12-membered lactams 12 as mixtures of E/Z-isomers. The
      scheme was also transferred to the solid-phase. In this case the macrolactams are
      formed via cyclorelease. For a pair of E/Z-isomers the solution conformation was
      determined by ROESY spectroscopy.

PMID- 12182677
TI  - Flexible synthesis of phenanthrenes by a PtCl(2)-catalyzed cycloisomerization
      reaction.
AB  - Readily available biphenyl derivatives containing an alkyne unit at one of their
      ortho positions are converted into substituted phenanthrenes upon exposure to
      catalytic amounts of either PtCl(2), AuCl(3), GaCl(3), or InCl(3) in toluene.
      This 6-endo-dig cyclization likely proceeds through initial pi-coordination of
      the alkyne unit followed by interception of the resulting eta(2)-metal complex by
      the adjacent arene ring. The reaction is inherently modular, allowing for
      substantial structural variations and for the incorporation of substituents at
      any site of the phenanthrene product except C-9. Moreover, the reaction is
      readily applied to the heterocyclic series as exemplified by the preparation of
      benzoindoles, naphthothiophenes as well as bridgehead nitrogen heterocycles.

PMID- 12182678
TI  - Generation and intermolecular reactions of 3-indolylacyl radicals.
AB  - The generation of 3-indolylacyl radicals from the corresponding phenyl
      selenoesters and the scope of their participation in intermolecular addition
      reactions to carbon-carbon double bonds under both reductive and nonreductive
      conditions have been studied.

PMID- 12182679
TI  - Beckmann rearrangement of oximes under very mild conditions.
AB  - A variety of ketoximes, easily prepared from the corresponding ketones, undergo
      the Beckmann rearrangement upon treatment with 2,4,6-trichloro[1,3,5]triazine in
      N,N-dimethylformamide at room temperature in excellent yields. This procedure can
      be applied to aldoximes for obtaining the corresponding nitriles.

PMID- 12182681
TI  - Ab initio thermochemistry of some halogenated cyclopropanes.
AB  - The standard enthalpies of formation for a series of chloro- and fluoro
      substituted cyclopropanes have been calculated by using high-level ab initio
      G3/B3LYP methods. The relative stabilities of isomers and the influence of
      substituents on thermochemistry in several classes of substituted derivatives are
      discussed.

PMID- 12182680
TI  - Stereoselective synthesis of new selenium-containing heterocycles by
      cyclocarbonylation of aminoalkynes with carbon monoxide and selenium.
AB  - The reaction of 3-aminoalkynes 2 with carbon monoxide and selenium yielded 5
      alkylideneselenazolin-2-ones 3 stereoselectively via cycloaddition of in situ
      generated carbamoselenoates to the carbon-carbon triple bond. 4-Aminoalkyne 7
      also afforded the corresponding six-membered selenium-containing heterocycle with
      the aid of CuI.

PMID- 12182682
TI  - Synthesis of poly(alkyl aryl ether) dendrimers.
AB  - Poly(alkyl aryl ether) dendrimers of up to four generations composed of a
      phloroglucinol core, branching components, and pentamethylene spacers are
      synthesized by a divergent growth methodology. A repetitive synthetic sequence of
      phenolic O-alkylation and O-benzyl deprotection reactions are adopted for the
      synthesis of these dendrimers. The peripheries of the dendrimers contain 6, 12,
      24, and 48 phenolic hydroxyl groups, either in the protected or unprotected form,
      for the first, second, third, and fourth generations, respectively. Because of
      the presence of hydrophilic exterior and relatively hydrophobic interior regions,
      alkaline aqueous solutions of these dendrimers are able to solubilize an
      otherwise insoluble pyrene molecule and these supramolecular complexes
      precipitate upon neutralization of the aqueous solutions.

PMID- 12182685
TI  - A vaccine against Alzheimer's disease: developments to date.
AB  - There are no significantly effective therapeutic or prophylactic agents for
      Alzheimer's disease (AD), the leading cause of age-related dementia. AD is
      characterised pathologically by plaque-like deposits of beta-amyloid in the brain
      as well as cytoskeletal ("neurofibrillary") alterations within nerve cells. A
      novel immunisation strategy directed at the beta-amyloid abnormalities underlying
      plaque pathology has recently been proposed for AD. This approach is supported by
      experimental studies utilising beta-amyloid as an immunogen, or antibodies to
      beta-amyloid, in transgenic experimental models that develop plaque pathology but
      not neurofibrillary alterations or severe neurodegeneration. Behavioural
      abnormalities in these mice related to deficits in spatial working memory were
      also ameliorated by immunisation with beta-amyloid. The promise of this novel
      approach to AD treatment and/or prevention has led to initial human trials
      utilising beta-amyloid as an immunogen.

PMID- 12182684
TI  - High-dose chemotherapy and stem cell support for breast cancer: where are we now?
AB  - To date, there is no definitive evidence that high-dose chemotherapy and
      haematopoietic stem cell support offers a survival advantage over conventional
      dose chemotherapy for metastatic or high-risk primary breast cancer. Studies of
      metastatic disease discussed in this review have an adequate duration of follow
      up given the short natural history of metastatic breast cancer. Thus, the results
      of these studies are unlikely to change with a longer observation period. On the
      other hand, studies of high-dose chemotherapy in the treatment of high-risk
      primary breast cancer need longer follow-up in light of the longer natural
      history of this type of disease. Results of unpublished studies and longer follow
      up of available studies may still demonstrate a survival advantage for high-dose
      chemotherapy in patients with metastatic or high-risk primary breast cancer. We
      continue to encourage participation in innovative clinical studies.

PMID- 12182686
TI  - Issues in the conduct of therapeutic trials in palliative care: an Australian
      perspective.
AB  - Palliative care has been slow to demonstrate that its common interventions are
      supported by high levels of evidence. There are multiple reasons for this-
      historical and cultural, as well as the recognised difficulties of conducting
      studies in dying persons. There are problems in isolating the effect of a single
      intervention from the many other changing dimensions which attend the progress of
      terminal illness, and problems also in defining particular outcomes free from the
      contaminating effect of other simultaneous changes in a patient's situation.
      Sickness is an interaction between disease and patient, and science sits more
      comfortably with the study of disease than with the understanding of the patient.
      Nevertheless, the therapies commonly employed for symptom management in
      individuals with advanced and terminal illness deserve more rigorous
      investigation to establish their efficacy. In Australia, new levels of government
      support for research have stimulated a closer examination of principles and
      practical guidelines for the conduct of research in this area of healthcare.

PMID- 12182687
TI  - Viral skin infections in the elderly: diagnosis and management.
AB  - Over the past several years, there have been advances in the diagnosis and
      treatment of cutaneous viral diseases in elderly patients. Herpes zoster is
      caused by reactivation in adults of the varicella-zoster virus (VZV) that causes
      chickenpox in children. For many years, aciclovir was the gold standard of
      antiviral therapy for the treatment of herpes zoster. Famciclovir and
      valaciclovir are newer antivirals, which offer less frequent administration.
      Postherpetic neuralgia (PHN) refers to pain lasting 2 months or more after an
      acute attack of herpes zoster. The pain may be constant or intermittent. The
      treatment of established PHN may include topical anaesthetics, analgesics,
      tricyclic antidepressants and anticonvulsants, and nonpharmacological therapy may
      be used to complement such treatment. Therapeutic strategies to prevent PHN
      include the use of oral corticosteroids, nerve blocks, and treatment with
      standard antiviral therapy. The three most recently discovered human herpes
      viruses (HHV-6, HHV-7 and HHV-8), in common with the other members of the family,
      may cause a primary infection, establish latent infection in a specific set of
      cells in their host, and then reactivate if conditions of altered immunity
      develop. These viruses have been associated with an array of disorders, which are
      important for the clinician to recognise. Cytomegalovirus (CMV) is a member of
      the herpesvirus family that is very prevalent worldwide. More than 80% of primary
      infections and 20% of reactivation-producing symptoms occur in transplant
      populations. Treatment options include intravenous administration of ganciclovir,
      foscarnet or cidofovir. Herpes simplex virus (HSV) most commonly affects the
      genital and perioral regions. In the elderly, HSV infection is typically manifest
      at the vermilion border of the lip. The main concern of recurrent herpes labialis
      in the elderly is related to potential autoinoculation of the eye or genital
      area. Treatment with aciclovir, famciclovir or valaciclovir is indicated for
      these infections. Molluscum contagiosum is caused by a poxvirus, which produces
      cutaneous lesions that appear as small, firm, umbilicated papules.
      Immunocompromised patients often do not respond to the usual destructive
      therapies, and intravenous or topical cidofovir may be useful in these patients.

PMID- 12182689
TI  - Tolerability of hypnosedatives in older patients.
AB  - Sleep disturbances are common and prevalence rates increase with age. Especially
      in the elderly, somatic diseases and medications with adverse effects relating to
      sleep are frequent reasons for disturbed and nonrefreshing sleep. It should be
      emphasised that these reasons must be excluded before symptomatic therapy is
      started. In some cases the use of hypnosedatives may be included as part of the
      treatment of a somatic disease and may cause sleep disturbances. Pharmacotherapy
      is one of the main approaches in the management of primary insomnia and should be
      part of a broader treatment strategy including nonpharmacological methods. This
      article focuses on the tolerability of frequently prescribed hypnosedatives in
      the elderly with primary insomnia and addresses the primary care physician. In
      general, recommendations for the pharmacotherapy of insomnia in elderly patients
      include using a reduced dosage. For some substances (e.g. zolpidem, zopiclone,
      zaleplon, temazepam and triazolam) the recommended dosage is half that
      recommended for younger patients. The properties of the selected hypnosedative
      should be taken into consideration and matched with the type of sleep disturbance
      experienced by the patient. Ultrashort-acting drugs may be useful when initiating
      sleep is the main problem, whereas short- and intermediate-acting substances are
      recommended for maintaining sleep. Possible interactions with pre-existing
      medication must also be taken into consideration. Some agents such as
      antipsychotics, antidepressants, melatonin and herbal agents may be used in
      specific indications. However, only a few of these substances have proven
      tolerability in the elderly and further investigations are recommended.

PMID- 12182688
TI  - Aging and intestinal motility: a review of factors that affect intestinal
      motility in the aged.
AB  - Normal aging is associated with significant changes in the function of most
      organs and tissues. In this regard, the gastrointestinal tract is no exception.
      The purpose of this review is to detail the important age-related changes in
      motor function of the various parts of the gastrointestinal tract and to
      highlight some of the important motility changes that may occur, either in
      relation to common age-related disorders, or as a result of certain drugs
      commonly prescribed in the aged. A major confounding factor in the interpretation
      of motor phenomena throughout the gastrointestinal tract in this age group is the
      frequent coexistence of neurological, endocrinological and other disease states,
      which may be independently associated with dysmotility. Overall, current data are
      insufficient to implicate normal aging as a cause of dysmotility in the elderly.
      Normal aging is associated with various changes in gastrointestinal motility, but
      the clinical significance of such changes remains unclear. More important is the
      impact of various age-related diseases on gastrointestinal motility in the
      elderly: for example, long-standing diabetes mellitus may reduce gastric emptying
      in up to 50% of patients; depression significantly prolongs whole-gut transit
      time; hypothyroidism may prolong oro-caecal transit time; and chronic renal
      failure is associated with impaired gastric emptying. In addition, various,
      frequently used drugs in the elderly cause disordered gastrointestinal motility.
      These drugs include anticholinergics, especially antidepressants with an
      anticholinergic effect, opioid analgesics and calcium antagonists.

PMID- 12182690
TI  - Smooth blood pressure control obtained with extended-release felodipine in
      elderly patients with hypertension: evaluation by 24-hour ambulatory blood
      pressure monitoring.
AB  - OBJECTIVE: To assess, by smoothness index (SI), distribution of the
      antihypertensive effect of extended-release (ER) felodipine over 24 hours in
      elderly patients with hypertension. METHODS: After a 4-week washout phase, 35
      elderly patients (mean age 69 +/- 4 years) with mild-to-moderate hypertension
      received 2 weeks' treatment with ER felodipine 5mg once daily. The dosage of ER
      felodipine was doubled to 10 mg/day and given for a further 2 weeks in non
      responders (sitting clinic blood pressure > 140/90mm Hg). The study had an open
      label design with no placebo control. After each period, clinic and ambulatory
      blood pressures were measured. Trough-to-peak (T/P) ratio was computed by
      dividing the blood pressure (BP) change at trough (22 to 24 hours after drug
      intake) by the change at peak (2 adjacent hours with a maximal BP reduction
      between the second and eighth hour after drug intake). SI was calculated as the
      ratio between the average of the 24, hourly, treatment-induced BP changes and its
      standard deviation. RESULTS: After the initial 2-week treatment period, clinic
      and 24-hour ambulatory BP values were higher in non-responders (145 +/- 11/87 +/-
      8 and 135 +/- 17/80 +/- 6mm Hg, respectively) than in responders (133 +/- 6/81 +/
      3 and 130 +/- 9/77 +/- 7mm Hg). In non-responders, clinic and 24-hour BP values
      were lowered after a further 2 weeks of treatment with ER felodipine 10 mg/day
      (128 +/- 11/78 +/- 6 and 128 +/- 12/75 +/- 5mm Hg). SI was high in responders
      (0.8 +/- 0.8/0.7 +/- 0.7 for systolic/diastolic BP) and low in non-responders
      (0.5 +/- 0.6/0.3 +/- 0.6) during the first 2-week treatment period. It increased
      in non-responders after an additional 2 weeks of treatment with ER felodipine 10
      mg/day (1.0 +/- 0.8/0.7 +/- 0.6). Median T/P ratios were 0.73 and 0.61 (systolic
      BP and diastolic BP) in responders and 0.41 and 0.61 in non-responders after 2
      weeks of treatment. At variance with SI, T/P ratios did not increase in non
      responders after doubling the dosage of ER felodipine (0.34 and 0.18). ER
      felodipine did not increase 24-hour heart rate. A total of nine adverse events
      were recorded in six patients (17%), but no patients withdrew from the study.
      CONCLUSION: ER felodipine 5 to 10 mg/day smoothly and safely reduces 24-hour
      ambulatory BP in elderly patients with hypertension.

PMID- 12182691
TI  - Preserving our mission.

PMID- 12182692
TI  - Interventions to promote physical activity among African American women.
AB  - The lack of routine physical activity among African American women places them at
      risk for negative health outcomes associated with inactivity. The number of
      studies focused on African American women has increased dramatically in the past
      decade. This review examined the intervention research literature testing
      strategies to increase activity among African American women. Eighteen studies
      with 1,623 subjects were retrieved. Diverse interventions, settings, and measures
      were reported. Common methodologic weaknesses included lack of randomization of
      subjects, single-group design, instruments without documented validity and
      reliability, significant attrition, and questionable timing of outcome variable
      measurement. Strategies to design and deliver culturally appropriate
      interventions are reviewed. Suggestions for future research, such as examining
      intragroup differences and communal resources, are provided.

PMID- 12182693
TI  - Maternal characteristics and maternal limit-setting styles.
AB  - In a longitudinal study of 126 mothers and toddlers during toddlerhood, maternal
      limit-setting styles were assessed at 12, 24, and 36 months in relation to
      selected maternal characteristics. Mothers using teaching-based limit-setting
      styles at 12 months reported more optimal relationship histories of care and
      overprotection/control in their own families of origin. The main contributor to a
      maternal teaching-based limit-setting style in this sample was years of formal
      education, followed by a more multicausal conceptualization of how children
      develop. Thus, while years of formal education appear to facilitate the use of a
      teaching-based limit-setting style, formal education is not the only way to
      develop these skills. Maternal conceptualization of development may be amenable
      to intervention through a number of alternative learning activities. Further
      research is needed to explore the effects of different types of educational and
      learning opportunities on current maternal behavior, with the goal of optimizing
      socialization skills related to the development of toddler self-regulation.

PMID- 12182694
TI  - Effectiveness of a mobile medical van in providing screening services for STDs
      and HIV.
AB  - This retrospective study assesses the efficacy of a mobile medical van in
      screening high risk individuals and identifying new cases of HIV and other
      sexually transmitted diseases (STDs) in an urban setting from July 1996 through
      March 1997. High risk sex and drug use were common, while consistent condom use
      was rare. Relatively few patients were screened for STDs; positive cases
      represented only a small proportion of the STD cases identified in the study
      community. The mobile program, however, accounted for 11.5% of all HIV tests
      conducted at public test sites in the city. Mobile medical programs have the
      potential to improve STD and HIV control efforts by providing services to high
      risk individuals who may lack access to care elsewhere. Doing so, however, will
      require more active case finding techniques, including new, less invasive
      techniques to test asymptomatic individuals.

PMID- 12182695
TI  - Assessment of community contamination: a critical approach.
AB  - The purpose of this paper is to review data from two Superfund sites and describe
      the latitude of interpretation of "environmental risk" by residents living in the
      area, governmental agencies, and the media. The first community was located
      within a 5-mi perimeter of the Rocky Flats Environmental Technology Site (RFETS)
      outside Denver, Colorado. The second community was located on the south side of
      Tucson, Arizona, adjacent to the Tucson International Airport area (TIAA)
      Superfund site. Critical theory was the perspective used in this analysis and
      proposal of public health actions to attain social justice. Differences between
      the two populations' experiences with risk and contamination coincided with
      divergent levels of trust in government. RFETS residents demanded monitoring,
      whereas the minority residents at TIAA were ambivalent about their trust in
      government cleanup activities. Unraveling the purpose of "facts" and the social
      force of "truth" can direct nurses to address environmental justice issues. By
      policing governmental and business activities in halting or cleaning up
      environmental contamination, nurses may become mouthpieces for the concerns
      underlying the fragile surface of "virtual trust" in contaminated communities.
      Cutting through competing rhetoric to police environmental safety, the core
      function of assurance becomes what nurses do, not what they say.

PMID- 12182696
TI  - Mexican American elders' use of skilled home care nursing services.
AB  - Hispanic elders use skilled home care nursing (SHCN) services less often than
      Anglo elders. The purpose of this study was to identify factors that influence
      whether disabled Mexican American elders decide to use SHCN services. The
      research process included reviewing the historical context in one Mexican
      American community, interviewing key and primary informants, presenting a report
      to the community and getting feedback, and assessing whether the community
      perceived a need for increased use of SHCN services by their disabled elders.
      Seven barriers to the use of SHCN services were identified: expectations of
      discrimination, lack of knowledge about services, expectations embedded in
      familism, lack of sense of prevention, lack of health insurance, preference for
      traditional remedies, and neglect/abuse. A community advisory committee validated
      the barriers identified during interviews and the need for increased use of SHCN
      services. Results provide new insight into the sociopolitical and cultural
      complexities that influence health care utilization decisions by Mexican American
      elders and their families and uncover traditional, oversimplified beliefs and
      practices by mainstream professionals and policymakers. Interventions that
      decrease inequities in a southern Arizona community may be transferable to other
      vulnerable populations in the United States and globally.

PMID- 12182697
TI  - Evaluation of a clinic-based parent education program to reduce the risk of
      infant and toddler maltreatment.
AB  - Community-based parent education programs are a common component of service plans
      for abusive and potentially abusive parents. Despite their widespread use, few
      studies have evaluated the effect of such programs to change actual parenting
      behavior even though this is a key intervention goal. The purpose of this study
      was to evaluate whether a relatively brief and inexpensive clinic-based education
      program could benefit parents of infants and toddlers by alleviating parental
      stress and improving parent-child interaction. Participants were 199 parents of
      children 1 through 36 months of age who were at risk for parenting problems and
      child maltreatment due to serious life stress including poverty, low social
      support, personal histories of childhood maltreatment, and substance abuse.
      Program effects were evaluated in terms of improvement in self-reported parenting
      stress and observed parent-child interaction. Positive effects were documented
      for the group as a whole and within each of three subgroups: two community
      samples and a group of mothers and children in residential drug treatment.
      Additional analyses illustrated a dose-response relationship between program
      attendance and magnitude of gain in observed parenting skills.

PMID- 12182698
TI  - Development and evaluation of an instrument to measure seniors' attitudes toward
      the use of bathroom grab bars.
AB  - Bath grab bars can minimize the effects of many age-related deficits that may
      contribute to bath-related falls. Despite their potential value, bathroom safety
      devices remain largely underutilized by many community-living older adults and
      knowledge concerning attitudinal factors that influence the use of grab bars is
      sparse. This void of knowledge is due, at least in part, to the lack of
      instruments to measure the psychosocial constructs influencing bathroom safety
      device use. This study examined the psychometric properties of a newly developed
      Grab Bar Use Attitude scale (GUAS). Instrument formation, including item
      generation, evaluation by a panel of experts, and pilot testing of the draft
      instrument to establish its face and content validity, was followed by instrument
      validation using 546 community-living seniors. Results of principal components
      analysis of the GUAS revealed a two-factor solution, explaining 56% of the
      variance. The two constructs may best be described as functional/safety and
      psychosocial consequences of using grab bars. Psychometric analyses of the 9-item
      scale provided empirical evidence of the internal consistency of the total scale
      and each subscale. Finally, the GUAS distinguished between regular grab bar users
      and nonregular users. Implications for use are discussed.

PMID- 12182699
TI  - Insect-resistant transgenic plants in a multi-trophic context.
AB  - So far, genetic engineering of plants in the context of insect pest control has
      involved insertion of genes that code for toxins, and may be characterized as the
      incorporation of biopesticides into classical plant breeding. In the context of
      pesticide usage in pest control, natural enemies of herbivores have received
      increasing attention, because carnivorous arthropods are an important component
      of insect pest control. However, in plant breeding programmes, natural enemies of
      herbivores have largely been ignored, although there are many examples that show
      that plant breeding affects the effectiveness of biological control. Negative
      influences of modified plant characteristics on carnivorous arthropods may induce
      population growth of new, even more harmful pest species that had no pest status
      prior to the pesticide treatment. Sustainable pest management will only be
      possible when negative effects on non-target, beneficial arthropods are
      minimized. In this review, we summarize the effects of insect-resistant crops and
      insect-resistant transgenic crops, especially Bt crops, from a food web
      perspective. As food web components, we distinguish target herbivores, non-target
      herbivores, pollinators, parasitoids and predators. Below-ground organisms such
      as Collembola, nematodes and earthworms should also be included in risk
      assessment studies, but have received little attention. The toxins produced in Bt
      plants retain their toxicity when bound to the soil, so accumulation of these
      toxins is likely to occur. Earthworms ingest the bound toxins but are not
      affected by them. However, earthworms may function as intermediaries through
      which the toxins are passed on to other trophic levels. In studies where effects
      of insect-resistant (Bt) plants on natural enemies were considered, positive,
      negative and no effects have been found. So far, most studies have concentrated
      on natural enemies of target herbivores. However, Bt toxins are structurally
      rearranged when they bind to midgut receptors, so that they are likely to lose
      their toxicity inside target herbivores. What happens to the toxins in non-target
      herbivores, and whether these herbivores may act as intermediaries through which
      the toxins may be passed on to the natural enemies, remains to be studied.

PMID- 12182700
TI  - Transgenic crops, biotechnology and ownership rights: what scientists need to
      know.
AB  - Ownership of intellectual and tangible property (IP/TP) rights in agricultural
      biotechnology (ag-biotech) and transgenic plants has become critically important.
      For scientists in all institutions, whether industrialized or developing country,
      public or private sector, an understanding of IP/TP rights is fundamental in both
      research and development. Transgenic plants and ag-biotech products embody
      numerous components and processes, each of which may have IP/TP rights attached.
      To identify these rights, a transgenic plant or ag-biotech product must be
      dissected into its essential components and processes, with each 'piece' analysed
      under the IP/TP 'microscope'. This product deconstruction is an integral step in
      product clearance (PC) analysis leading to freedom to operate (FTO). To
      facilitate a PC analysis, the following points are important: (1) knowing what
      one has and where it's from, (2) organizing material transfer agreements and
      licences, (3) researching scientific and patent databases and relevant
      literature, (4) instituting a laboratory notebook policy, (5) keeping track of
      ownership of germplasm and plant genetic resources, and (6) promoting ongoing
      IP/TP management, awareness and training. However, a FTO opinion does not solve
      the IP/TP issues of releasing a transgenic plant or ag-biotech product; rather,
      it is a management tool for assessing the risks of litigation. When transferring
      transgenic plants or ag-biotech to developing nations, scientists from
      industrialized countries have the heightened responsibility of verifying that
      IP/TP issues are fully addressed and documented. Successful technology transfer
      goes beyond research, development and licensing; it is an holistic package
      leading to long-term partnerships in international development. Managing IP/TP
      requires capacity-building in scientists and technology transfer offices, in both
      industrialized and developing countries.

PMID- 12182701
TI  - Five years of Bt cotton in China - the benefits continue.
AB  - Bt cotton is spreading very rapidly in China, in response to demand from farmers
      for technology that will reduce both the cost of pesticide applications and
      exposure to pesticides, and will free up time for other tasks. Based on surveys
      of hundreds of farmers in the Yellow River cotton-growing region in northern
      China in 1999, 2000 and 2001, over 4 million smallholders have been able to
      increase yield per hectare, and reduce pesticide costs, time spent spraying
      dangerous pesticides, and illnesses due to pesticide poisoning. The expansion of
      this cost-saving technology is increasing the supply of cotton and pushing down
      the price, but prices are still sufficiently high for adopters of Bt cotton to
      make substantial gains in net income.

PMID- 12182703
TI  - Sequence elements within an HSP70 promoter counteract transcriptional transgene
      silencing in Chlamydomonas.
AB  - We have shown previously that the HSP70A (A) promoter, when fused upstream of
      other promoters, significantly improves their performance in driving transgene
      expression in Chlamydomonas. Here, we employed the bacterial resistance gene ble,
      driven by the RBCS2 (R) promoter or an AR promoter fusion, to determine, by which
      mechanism(s) the A promoter may exert its enhancing effect. We observed that
      transformation rates of AR-ble constructs were significantly higher than those of
      R-ble constructs. However, ble mRNA levels in pools of transformants generated
      with either construct type were the same. Co-transformation experiments revealed
      that the R-ble transgene was silenced in 80% of the transformants, whereas this
      fraction was reduced to 36% in transformants harbouring the AR-ble transgene. We
      conclude that the A promoter acts by decreasing the probability that a transgene
      becomes transcriptionally silenced. We mapped two elements within the A promoter
      that are responsible for this effect. The core of the first element appears to be
      located between nucleotides - 7 and + 67 relative to the HSP70A transcriptional
      start site. Its activity is strongly dependent on its spatial setting with
      respect to the R promoter and is increased by upstream sequences (- 196 to - 8).
      The second element is independent of the first and is located to the region from 
      754 to - 197. Its activity is spacing-independent and additive to the first
      element.

PMID- 12182702
TI  - Tomato LeAGP-1 arabinogalactan-protein purified from transgenic tobacco
      corroborates the Hyp contiguity hypothesis.
AB  - Functional analysis of the hyperglycosylated arabinogalactan-proteins (AGPs)
      attempts to relate biological roles to the molecular properties that result
      largely from O-Hyp glycosylation putatively coded by the primary sequence. The
      Hyp contiguity hypothesis predicts contiguous Hyp residues as attachment sites
      for arabino-oligosaccharides (arabinosides) and clustered, non-contiguous Hyp
      residues as arabinogalactan polysaccharide sites. Although earlier tests of
      naturally occurring hydroxyproline-rich glycoproteins (HRGPs) and HRGPs designed
      by synthetic genes were consistent with a sequence-driven code, the predictive
      value of the hypothesis starting from the DNA sequences of known AGPs remained
      untested due to difficulties in purifying a single AGP for analysis. However,
      expression in tobacco (Nicotiana tabacum) of the major tomato (Lycopersicon
      esculentum) AGP, LeAGP-1, as an enhanced green fluorescent protein fusion
      glycoprotein (EGFP)-LeAGP-1, increased its hydrophobicity sufficiently for
      chromatographic purification from other closely related endogenous AGPs. We also
      designed and purified two variants of LeAGP-1 for future functional analysis: one
      lacking the putative glycosylphosphatidylinositol (GPI)-anchor signal sequence;
      the other lacking a 12-residue internal lysine-rich region. Fluorescence
      microscopy of plasmolysed cells confirmed the location of LeAGP-1 at the plasma
      membrane outer surface and in Hechtian threads. Hyp glycoside profiles of the
      fusion glycoproteins gave ratios of Hyp-polysaccharides to Hyp-arabinosides plus
      non-glycosylated Hyp consistent with those predicted from DNA sequences by the
      Hyp contiguity hypothesis. These results demonstrate a route to the purification
      of AGPs and the use of the Hyp contiguity hypothesis for predicting the Hyp O
      glycosylation profile of an HRGP from its DNA sequence.

PMID- 12182705
TI  - Modifying the pollen coat protein composition in Brassica.
AB  - The interactions between pollen and stigma are essential for plant reproduction
      and are made possible by compounds, such as proteins and lipids, located on their
      surfaces. The pollen coat is formed in part by compounds synthesized in, and
      released from, the tapetum, which become transferred to the pollen coat late in
      pollen development. In the Brassicaceae the predominant proteins of the mature
      pollen coat are the tapetal oleosin-like proteins, which are highly expressed in,
      and ultimately transferred from, the tapetum. Here we report the modification of
      the protein composition of the pollen coat by the addition of an active enzyme
      which was synthesized in the tapetum. The marker enzyme beta-glucuronidase (GUS)
      was successfully targeted to the pollen coat in transgenic Brassica carinata
      plants expressing GUS translationally fused to a B. napus tapetal oleosin-like
      protein (BnOlnB;4). To our knowledge this is the first demonstration of the
      targeting of an enzyme to the pollen coat.

PMID- 12182704
TI  - On the origin of class B floral homeotic genes: functional substitution and
      dominant inhibition in Arabidopsis by expression of an orthologue from the
      gymnosperm Gnetum.
AB  - Class B floral homeotic genes are involved in specifying stamen and petal
      identity in angiosperms (flowering plants). Here we report that gymnosperms, the
      closest relatives of the angiosperms, contain at least two different clades
      representing putative orthologues of class B genes, termed GGM2-like and DAL12
      like genes. To obtain information about the functional conservation of the class
      B genes in seed plants, the representative of one of these clades from Gnetum,
      termed GGM2, was expressed under the control of the CaMV 35S promoter in
      Arabidopsis wild-type plants and in different class B mutants. In wild-type
      plants and in a conditional mutant grown at a permissive temperature, gain-of
      function phenotypes were obtained in whorls 1 and 4, where class B genes are
      usually not expressed. In contrast, loss-of-function phenotypes were observed in
      whorls 2 and 3, where class B genes are expressed. In different class B gene null
      mutants of Arabidopsis, and in the conditional B mutant grown at the non
      permissive temperature, a partial complementation of the mutant phenotype was
      obtained. In situ hybridization studies and class B gene promoter test fusion
      experiments demonstrated that the gain-of-function phenotypes are not due to an
      upregulation of the endogenous B genes from Arabidopsis, and hence probably
      involve interactions between GGM2 protein homodimers and class B protein target
      genes other than the Arabidopsis class B genes itself. To our knowledge, this is
      the first time that partial complementation of a homeotic mutant by an
      orthologous gene from a distantly related species has been reported. These data
      suggest that GGM2 has a function in the gymnosperm Gnetum which is related to
      that of class B floral organ identity genes of angiosperms. That function may be
      in the specification of male reproductive organ identity, and in distinguishing
      male from female reproductive organs.

PMID- 12182706
TI  - A novel interaction partner for the C-terminus of Arabidopsis thaliana plasma
      membrane H+-ATPase (AHA1 isoform): site and mechanism of action on H+-ATPase
      activity differ from those of 14-3-3 proteins.
AB  - Using the two-hybrid technique we identified a novel protein whose N-terminal 88
      amino acids (aa) interact with the C-terminal regulatory domain of the plasma
      membrane (PM) H+-ATPase from Arabidopsis thaliana (aa 847-949 of isoform AHA1).
      The corresponding gene has been named Ppi1 for Proton pump interactor 1. The
      encoded protein is 612 aa long and rich in charged and polar residues, except for
      the extreme C-terminus, where it presents a hydrophobic stretch of 24 aa. Several
      genes in the A. thaliana genome and many ESTs from different plant species share
      significant similarity (50-70% at the aa level over stretches of 200-600 aa) to
      Ppi1. The PPI1 N-terminus, expressed in bacteria as a fusion protein with either
      GST or a His-tag, binds the PM H+-ATPase in overlay experiments. The same fusion
      proteins and the entire coding region fused to GST stimulate H+-ATPase activity.
      The effect of the His-tagged peptide is synergistic with that of fusicoccin (FC)
      and of tryptic removal of a C-terminal 10 kDa fragment. The His-tagged peptide
      binds also the trypsinised H+-ATPase. Altogether these results indicate that PPI1
      N-terminus is able to modulate the PM H+-ATPase activity by binding to a site
      different from the 14-3-3 binding site and is located upstream of the trypsin
      cleavage site.

PMID- 12182707
TI  - Arf1 GTPase plays roles in the protein traffic between the endoplasmic reticulum
      and the Golgi apparatus in tobacco and Arabidopsis cultured cells.
AB  - Arf GTPases are known to be key regulators of vesicle budding in various steps of
      membrane traffic in yeast and animal cells. We cloned the Arabidopsis Arf1
      homologue, AtArf1, and examined its function. AtArf1 complements yeast arf1 arf2
      mutants and its GFP-fusion is localized to the Golgi apparatus in plant cells
      like its animal counterpart. The expression of dominant negative mutants of
      AtArf1 in tobacco and Arabidopsis cultured cells affected the localization of co
      expressed GFP-tagged proteins in a variety of ways. AtArf1 Q71L and AtArf1 T31N,
      GTP- and GDP-fixed mutants, respectively, changed the localization of a cis-Golgi
      marker, AtErd2-GFP, from the Golgi apparatus to the endoplasmic reticulum but not
      that of GFP-AtRer1B or GFP-AtSed5. GFP-AtRer1B and GFP-AtSed5 were accumulated in
      aberrant structures of the Golgi by AtArf1 Q71L. A soluble vacuolar protein,
      sporamin-GFP, was also located to the ER by AtArf1 Q71L. These results indicate
      that AtArf1 play roles in the vesicular transport between the ER and the Golgi
      and in the maintenance of the normal Golgi organization in plant cells.

PMID- 12182708
TI  - Disruption of the Arabidopsis AtKu80 gene demonstrates an essential role for
      AtKu80 protein in efficient repair of DNA double-strand breaks in vivo.
AB  - Double-strand breaks (DSBs) in DNA may occur spontaneously in the cell or be
      induced experimentally by gamma-irradiation, and represent one of the most
      serious threats to genomic integrity. Non-homologous end joining (NHEJ) rather
      than homologous recombination appears to be the major pathway for DSB repair in
      humans and plants, and it may also be the major route whereby T-DNA integrates
      into the plant genome during cell transformation. In yeast and mammals, the
      exposed ends of damaged DNA are bound with high affinity by a dimer of Ku70 and
      Ku80 proteins, which protects the ends from exonucleases and juxtaposes the two
      ends of the DSB, independent of sequence homology. Here we report the functional
      characterization of Ku70 and Ku80 from Arabidopsis thaliana, and demonstrate that
      AtKu80 and AtKu70 form a heterodimer with DNA binding activity that is specific
      for DNA ends. An atku80 knockout mutant shows hypersensitivity to the DNA
      damaging agents menadione and bleomycin, consistent with a role for AtKu80 in the
      repair of DSBs in vivo in Arabidopsis.

PMID- 12182710
TI  - Transgene integration in aspen: structures of integration sites and mechanism of
      T-DNA integration.
AB  - To obtain insight into the mechanism of transferred DNA (T-DNA) integration in a
      long-lived tree system, we analysed 30 transgenic aspen lines. In total, 27 right
      T-DNA/plant junctions, 20 left T-DNA/plant junctions, and 10 target insertions
      from control plants were obtained. At the right end, the T-DNA was conserved up
      to the cleavage site in 18 transgenic lines (67%), and the right border repeat
      was deleted in nine junctions. Nucleotides from the left border repeat were
      present in 19 transgenic lines out of 20 cases analysed. However, only four (20%)
      of the left border ends were conserved to the processing end, indicating that the
      T-DNA left and right ends are treated mechanistically differently during the T
      DNA integration process. Comparison of the genomic target sites prior to
      integration to the T-DNA revealed that the T-DNA inserted into the plant genome
      without any notable deletion of genomic sequence in three out of 10 transgenic
      lines analysed. However, deletions of DNA ranging in length from a few
      nucleotides to more than 500 bp were observed in other transgenic lines. Filler
      DNAs of up to 235 bp were observed on left and/or right junctions of six
      transgenic lines, which in most cases originated from the nearby host genomic
      sequence or from the T-DNA. Short sequence similarities between recombining
      strands near break points, in particular for the left T-DNA end, were observed in
      most of the lines analysed. These results confirm the well-accepted T-DNA
      integration model based on single-stranded annealing followed by ligation of the
      right border which is preserved by the VirD2 protein. However, a second category
      of T-DNA integration was also identified in nine transgenic lines, in which the
      right border of the T-DNA was partly truncated. Such integration events are
      described via a model for the repair of genomic double-strand breaks in somatic
      plant cells based on synthesis-dependent strand-annealing. This report in a long
      lived tree system provides major insight into the mechanism of transgene
      integration.

PMID- 12182709
TI  - Characterization of a HKT-type transporter in rice as a general alkali cation
      transporter.
AB  - We report the characterization of rice OsHKT1 (Oryza sativa ssp. indica)
      homologous to the wheat K+/Na+-symporter HKT1. Expression of OsHKT1 in the yeast
      strain CY162 defective in K+-uptake restored growth at mM and micro M
      concentrations of K+ and mediated hypersensitivity to Na+. When expressed in
      Xenopus oocytes, rice OsHKT1 showed uptake characteristics of a Na+-transporter
      but mediated transport of other alkali cations as well. OsHKT1 expression was
      analysed in salt-tolerant rice Pokkali and salt-sensitive IR29 in response to
      external cation concentrations. OsHKT1 is expressed in roots and leaves. Exposure
      to Na+, Rb+, Li+, and Cs+ reduced OsHKT1 transcript amounts in both varieties
      and, in some cases, incompletely spliced transcripts were observed. By in situ
      hybridizations the expression of OsHKT1 was localized to the root epidermis and
      the vascular tissue inside the endodermis. In leaves, OsHKT1 showed strongest
      signals in cells surrounding the vasculature. The repression of OsHKT1 in the two
      rice varieties during salt stress was different in various cell types with main
      differences in the root vascular tissue. The data suggest control over HKT
      expression as a factor that may distinguish salt stress-sensitive and stress
      tolerant lines. Differences in transcript expression in space and time in
      different lines of the same species appear to be a component of ion homeostasis
      correlated with salt sensitivity and tolerance.

PMID- 12182739
TI  - The role of the gut flora in health and disease, and its modification as therapy.
AB  - The gut flora is a vast interior ecosystem whose nature is only beginning to be
      unravelled, due to the emergence of sophisticated molecular tools. Techniques
      such as 16S ribosomal RNA analysis, polymerase chain reaction amplification and
      the use of DNA microarrays now facilitate rapid identification and
      characterization of species resistant to conventional culture and possibly
      unknown species. Life-long cross-talk between the host and the gut flora
      determines whether health is maintained or disease intervenes. An understanding
      of these bacteria-bacteria and bacteria-host immune and epithelial cell
      interactions is likely to lead to a greater insight into disease pathogenesis.
      Studies of single organism-epithelial interactions have revealed the large range
      of metabolic processes that gut bacteria may influence. In inflammatory bowel
      diseases, bacteria drive the inflammatory process, and genetic predisposition to
      disease identified to date, such as the recently described NOD2/CARD15 gene
      variants, may relate to altered bacterial recognition. Extra-intestinal
      disorders, such as atopy and arthritis, may also have an altered gut milieu as
      their basis. Clinical evidence is emerging that the modification of this internal
      environment, using either antibiotics or probiotic bacteria, is beneficial in
      preventing and treating disease. This natural and apparently safe approach holds
      great appeal.

PMID- 12182740
TI  - The treatment of irritable bowel syndrome.
AB  - The efforts of clinical researchers, lay organizations and pharmaceutical
      companies have increased the public profile of irritable bowel syndrome and made
      it a respectable diagnosis. Diagnostic symptom criteria encourage a firm clinical
      diagnosis, which is the foundation of a logical management strategy. This begins
      with education. Reassurance that no structural disease threatens should be
      tempered with the reality that symptoms are likely to recur over many years.
      Patients expect diet and lifestyle advice, even if this is not specific to
      irritable bowel syndrome. Only a few of those with irritable bowel syndrome see
      doctors, and even fewer see specialists. Therefore, the treating physician should
      ascertain the reason for the visit, the patient's fears and the presence of any
      comorbid illness, such as depression, that might require treatment in its own
      right. No drug treatment is useful for all of the symptoms of irritable bowel
      syndrome, and many patients require no drug at all. If used, drugs should target
      the predominant symptom. Alosetron, a 5-HT3 antagonist, is effective in treating
      women with irritable bowel syndrome who also have diarrhoea. Tegaserod, a 5-HT4
      agonist, is useful for women with irritable bowel syndrome who are constipated.
      Most patients with irritable bowel syndrome need psychological support.
      Reassurance, discussion and relaxation techniques can be provided by the family
      doctor. Difficult psychopathology may require referral to a mental health
      professional, and the gastroenterologist can settle diagnostic uncertainties. In
      all cases, successful treatment depends on a confident diagnosis and the strength
      of the doctor-patient relationship.

PMID- 12182741
TI  - Clinical perspectives, mechanisms, diagnosis and management of irritable bowel
      syndrome.
AB  - This consensus document reviews the current status of the epidemiology, social
      impact, patient quality of life, pathophysiology, diagnosis and treatment of
      irritable bowel syndrome. Current evidence suggests that two major mechanisms may
      interact in irritable bowel syndrome: altered gastrointestinal motility and
      increased sensitivity of the intestine. However, other factors, such as
      psychosocial factors, intake of food and prior infection, may contribute to its
      development. Management of patients is based on a positive diagnosis of the
      symptom complex, careful history and physical examination to exclude 'red flags'
      as risk factors for organic disease, and, if indicated, investigations to exclude
      other disorders. Therapeutic choices include dietary fibre for constipation,
      opioid agents for diarrhoea and low-dose antidepressants or infrequent use of
      antispasmodics for pain, although the evidence basis for efficacy is limited or
      in some cases absent. Psychotherapy and hypnotherapy are the subject of ongoing
      study. Treatment should be tailored to patient needs and fears. Novel therapies
      are emerging, and drugs acting on serotonin receptors have proven efficacy and a
      scientific rationale and, if approved, should be useful in the overall management
      of patients with irritable bowel syndrome. Patient and physician education, early
      identification of psychosocial issues and better therapies are important
      strategies to reduce the suffering and societal cost of irritable bowel syndrome.

PMID- 12182742
TI  - Impact of Helicobacter pylori eradication on heartburn in patients with gastric
      or duodenal ulcer disease -- results from a randomized trial programme.
AB  - BACKGROUND: Helicobacter pylori infection has been proposed as a protective
      factor against the development of gastro-oesophageal reflux disease. AIM: To
      study heartburn and endoscopic findings before and after H. pylori eradication
      therapy in patients with peptic ulcer disease. METHODS: In a multicentre trial
      programme, patients (n = 1497) were randomized to the omeprazole triple therapy
      group or to the control group, and were followed for 1-6 months after treatment.
      Patients in whom the infection was eradicated were compared with those in whom
      infection persisted. The severity of heartburn was measured at baseline and at
      each return visit. Endoscopy was performed 6 months after therapy in two of the
      five studies. RESULTS: In patients with duodenal ulcer, there was a significantly
      lower prevalence of heartburn after successful eradication of H. pylori relative
      to that after failed eradication (estimated odds ratio, 0.48). The reduction in
      the prevalence of heartburn in patients with gastric ulcer was independent of the
      post-treatment H. pylori status. In studies in which ulcer relapse was included
      in the model, this factor emerged as a significant factor for heartburn. The
      observed incidence of oesophagitis at the last visit was not influenced by H.
      pylori status. CONCLUSIONS: Eradication of H. pylori in patients with peptic
      ulcer disease was associated with a reduced prevalence of heartburn. Prevention
      of ulcer relapse could be the true cause of this reduction.

PMID- 12182743
TI  - Appropriateness of urea breath test: a prospective observational study based on
      Maastricht 2000 guidelines.
AB  - BACKGROUND: The urea breath test is routinely used for diagnosing or confirming
      the eradication of Helicobacter pylori. AIM: To evaluate the appropriateness of
      urea breath test referrals. METHODS: The age, sex, symptoms, endoscopic findings,
      use of non-steroidal anti-inflammatory drugs, family history of gastric cancer or
      H. pylori infection and concomitant diseases of patients referred for urea breath
      testing in a 1-year period were recorded. The appropriateness of urea breath test
      referrals was judged according to Maastricht guidelines. RESULTS: One thousand,
      three hundred and twenty subjects (47 +/- 16 years) were referred in 2001: 578
      (43.8%) for the diagnosis and 742 (56.2%) for confirmation of the eradication of
      H. pylori. The urea breath test was considered to be appropriate in 836 (63.3%)
      patients, inappropriate in 192 (14.5%) and appropriate but avoidable in 292
      (22.1%). The appropriateness ratios of urea breath test referrals were 4.6 and
      9.0 (P < 0.0001) for general practitioners and gastroenterologists, respectively.
      Of the patients (n=230) with un investigated dyspepsia, who underwent urea breath
      testing according to a 'test and treat' strategy, 98 (42.6%) presented at least
      one risk factor for organic disease. CONCLUSIONS: In Italy, nearly 36% of urea
      breath test referrals are inappropriate or could be avoided if all dyspeptic
      patients with risk factors were referred for endoscopy or all dyspeptic patients
      undergoing endoscopy were tested for H. pylori infection with biopsy methods.
      Both general practitioners and, to a lesser extent, gastroenterologists require
      educational programmes to deal effectively with H. pylori.

PMID- 12182744
TI  - Helicobacter pylori eradication therapy improves atrophic gastritis and
      intestinal metaplasia: a 5-year prospective study of patients with atrophic
      gastritis.
AB  - AIM: : To investigate the effect of the eradication of Helicobacter pylori on
      histological gastritis. METHODS: : Twenty-six patients with moderate to severe
      atrophy received successful eradication therapy of H.pylori. Four patients
      dropped out and 22 were followed up prospectively for 5 years. The grades of
      gastritis were estimated from gastric biopsy specimens. The grade of intestinal
      metaplasia was also evaluated by dye-endoscopy using methylene blue
      (methylthioninium chloride). The serum levels of pepsinogen, gastrin and anti
      parietal cell antibody were also determined. RESULTS: : The grades of atrophy
      decreased in patients with successful eradication therapy in the gastric corpus
      (before vs. 5 years after eradication, 2.09 +/- 0.15 vs. 0.91 +/- 0.17; P < 0.01)
      and in the antrum (2.14 +/- 0.17 vs. 1.36 +/- 0.17; P < 0.01). The levels of
      intestinal metaplasia were also decreased in the corpus (0.91 +/- 0.24 vs. 0.50
      +/- 0.16; P < 0.05) and in the antrum (1.41 +/- 0.20 vs. 1.00 +/- 0.16; P <
      0.05), which was also demonstrated by the methylene blue (methylthioninium
      chloride) staining method (33.4 +/- 8.2% vs. 23.0 +/- 6.5%; P < 0.05). The
      improvement of corpus atrophy correlated well with the high serum level of
      pepsinogen I (P = 0.005), but showed no correlation with the levels of anti
      parietal cell antibody. CONCLUSIONS: : These results suggest that gastric atrophy
      and intestinal metaplasia are reversible events in some patients.

PMID- 12182745
TI  - Efficacy of quadruple therapy with pantoprazole, bismuth, tetracycline and
      metronidazole as rescue treatment for Helicobacter pylori infection.
AB  - AIM: To study the efficacy of a 7-day quadruple regimen combining pantoprazole,
      bismuth, tetracycline and metronidazole as rescue treatment for Helicobacter
      pylori infection after failure of standard triple therapy. METHODS: A prospective
      study was made of 140 patients infected with H. pylori and diagnosed with peptic
      ulcer or non-ulcer dyspepsia in whom triple therapy with proton pump inhibitor,
      clarithromycin and amoxicillin had failed. The patients were treated with
      quadruple therapy including pantoprazole, 40 mg twice daily, colloidal bismuth
      subcitrate, 120 mg four times daily, tetracycline, 500 mg four times daily, and
      metronidazole, 500 mg three times daily, for 7 days. Two months after completion
      of therapy, a 13C-urea breath test was performed to confirm eradication. RESULTS:
      With quadruple therapy, the H. pylori eradication rates were 82% (95% confidence
      interval (CI), 75-88%) by 'intention-to-treat' and 85% (95% CI, 79-91%) by 'per
      protocol'. No major side-effects were observed. No differences in eradication
      success were observed in relation to underlying disease (peptic ulcer: 85% (95%
      CI, 76-91%) vs. non-ulcer dyspepsia: 83% (95% CI, 68-93%)) or smoking habits
      (smokers: 86% (95% CI, 75-93%) vs. non-smokers: 83% (95% CI, 71-91%)).
      CONCLUSION: Quadruple therapy with pantoprazole, bismuth, tetracycline and
      metronidazole for 7 days is an effective H. pylori eradication treatment for
      patients in whom standard triple therapy has failed.

PMID- 12182746
TI  - Meta-analysis: the effect of probiotic administration on antibiotic-associated
      diarrhoea.
AB  - BACKGROUND: Antibiotic-associated diarrhoea can be attributed in part to
      imbalances in intestinal microflora. Therefore, probiotic preparations are used
      to prevent this diarrhoea. However, although several trials have been conducted,
      no conclusive evidence has been found of the efficacy of different preparations,
      e.g. Lactobacillus spp. and Saccharomyces spp. AIM: To conduct a meta-analysis of
      the data in the literature on the efficacy of probiotics in the prevention of
      antibiotic-associated diarrhoea. METHODS: A literature search was performed of
      electronic databases, Abstract Books and single paper references. Data were also
      obtained from the authors. Only placebo-controlled studies were included in the
      search. The Mantel-Haenszel test was used to estimate the relative risk for
      single studies and an overall combined relative risk, each study being submitted
      to the Mantel-Haenszel test for homogeneity. RESULTS: Twenty-two studies matched
      the inclusion criteria. Only seven studies (881 patients) were homogeneous. The
      combined relative risk was 0.3966 (95% confidence interval, 0.27-0.57).
      CONCLUSIONS: The results suggest a strong benefit of probiotic administration on
      antibiotic-associated diarrhoea, but further data are needed. The evidence for
      beneficial effects is still not definitive. Published studies are flawed by the
      lack of a placebo design and by peculiar population features.

PMID- 12182747
TI  - Patient-centred endpoints in economic evaluations of gastro-oesophageal reflux
      disease.
AB  - AIM: To perform a systematic review of the economic literature on gastro
      oesophageal reflux disease to evaluate (a) the use of patient-centred
      effectiveness end-points, or (b) the use of patient-centred economic end-points,
      and the influence of these end-points on the outcome of the model. METHODS: Three
      electronic databases (EMBASE, BIOSIS and Medline) were used, together with a
      manual search of meeting abstracts for relevant articles. The quality of the
      studies was determined by the Drummond criteria. RESULTS: Our initial search
      identified 179 articles and a manual search revealed 78 abstracts and articles. A
      total of 47 studies (36 fully published articles and 11 abstracts) met the seven
      Drummond criteria for inclusion in our evaluation. CONCLUSIONS: This systematic
      review demonstrates that many of the published economic evaluations available
      today take the perspective of the third-party payer and focus on pharmaceutical
      costs relevant to the third-party payer. Our study also demonstrates that there
      are a number of costs of illness determinations, such that pharmaceutical costs
      account for only a small proportion of the total costs of managing gastro
      oesophageal reflux disease. Future economic analyses should consider an
      evaluation of the patient's desire for complete symptom relief by including cost
      utility assessments or willingness to pay data.

PMID- 12182748
TI  - Effects of ABT-229, a motilin agonist, on acid reflux, oesophageal motility and
      gastric emptying in patients with gastro-oesophageal reflux disease.
AB  - AIM: The effect of ABT-229, a new macrolide with no antibacterial activity, on
      gastro-oesophageal reflux, oesophageal motility and gastric emptying in patients
      with gastro-oesophageal reflux disease was investigated. METHODS: Twenty-one
      patients were treated with a placebo and ABT-229 (2.5, 5 or 10 mg b.d.) in a
      randomized, incomplete crossover study design. Ambulatory 24-h pH manometry was
      performed and gastric emptying was assessed by the 13C-octanoic acid breath test
      on the seventh day of treatment. RESULTS: A significant decrease was found in the
      mean (+/- s.e.) percentage of reflux time (intra-oesophageal pH < 4) for ABT-229
      5 mg b.d. and 10 mg b.d., but not for 2.5 mg b.d., compared with placebo. For ABT
      229 5 mg, it was 8.5 +/- 0.5% vs. 10.7 +/- 0.7% (P < 0.038) and, for ABT-229 10
      mg, it was 6.6 +/- 0.5% vs. 8.4 +/- 0.5% (P < 0.019). There were no significant
      differences in any of the analysed manometric parameters. In addition, the
      gastric half-emptying time for all doses of ABT-229 did not differ significantly
      from that after placebo. CONCLUSIONS: ABT-229 is able to reduce slightly, but
      significantly, acid reflux in patients with gastro-oesophageal reflux disease.
      This effect does not appear to be due to a measurable improvement in oesophageal
      motility or gastric emptying.

PMID- 12182749
TI  - Reappraisal of non-invasive management strategies for uninvestigated dyspepsia: a
      cost-minimization analysis.
AB  - BACKGROUND: The benefits of the Helicobacter pylori test-and-treat strategy are
      attributable largely to the cure of peptic ulcer disease while limiting the use
      of endoscopy. AIM: To reappraise the test-and-treat strategy and empirical proton
      pump inhibitor therapy for the management of uninvestigated dyspepsia in the
      light of the decreasing prevalence of H. pylori infection, peptic ulcer disease
      and peptic ulcer disease attributable to H. pylori. METHODS: Using a decision
      analytical model, we estimated the cost per patient with uninvestigated dyspepsia
      managed with the test-and-treat strategy ($25/test; H.pylori treatment, $200) or
      proton pump inhibitor ($90/month). Endoscopy ($550) guided therapy for persistent
      or recurrent symptoms. RESULTS: In the base case (25%H. pylori prevalence, 20%
      likelihood of peptic ulcer disease, 75% of ulcers due to H.pylori), the cost per
      patient is $545 with the test-and-treat strategy and $529 with proton pump
      inhibitor, and both strategies yield similar clinical outcomes at 1 year. H.
      pylori prevalence, the likelihood of peptic ulcer disease and the proportion of
      ulcers due to H.pylori are important determinants of the least costly strategy.
      At an H. pylori prevalence below 20%, proton pump inhibitor is consistently less
      costly than the test-and-treat strategy. CONCLUSIONS: As the H. pylori
      prevalence, the likelihood of peptic ulcer disease and the proportion of ulcers
      due to H. pylori decrease, empirical proton pump inhibitor becomes less costly
      than the test-and-treat strategy for the management of uninvestigated dyspepsia.
      Given the modest cost differential between the strategies, the test-and-treat
      strategy may be favoured if patients without peptic ulcer disease derive long
      term benefit from H.pylori eradication.

PMID- 12182750
TI  - The use of ciclosporin in paediatric inflammatory bowel disease: an Italian
      experience.
AB  - AIM: To asses the efficacy and safety of ciclosporin in a paediatric population
      with inflammatory bowel disease. PATIENTS AND METHODS: Twenty-three Italian
      children treated with ciclosporin were studied retrospectively. The indications
      for treatment were severe unresponsive colitis, chronic active colitis or severe
      fistulizing Crohn's disease. The treatment duration, follow-up and causes of drug
      discontinuation were assessed. RESULTS: Sixteen patients were treated
      intravenously for a mean time of 10 +/- 7 days (1-24 days) and 19 orally for a
      mean time of 133 days (17-660 days). The mean follow-up of all patients was 13.2
      months. Ciclosporin was totally ineffective, being discontinued for surgery, in
      nine of 23 patients (39%); it was discontinued for partial response in three
      patients (13%). During treatment, clinical remission was achieved in eight
      children (35%) and maintained after drug withdrawal in four (17%). In severe
      unresponsive colitis, urgent colectomy was avoided in 12 (85%) of 14 patients who
      tolerated the drug. Side-effects appeared in six of 23 patients (26%), and three
      (13%) required ciclosporin to be discontinued due to neurotoxicity. CONCLUSIONS:
      Ciclosporin shows disappointing long-term results in the treatment of refractory
      inflammatory bowel disease, but can play an important role in preventing urgent
      surgery in unresponsive severe colitis. Severe side-effects can occur.

PMID- 12182751
TI  - The effectiveness of budesonide therapy for Crohn's disease.
AB  - AIM: To assess the effectiveness and safety of budesonide in comparison to
      corticosteroids, 5-aminosalicylic acid (5-ASA), or placebo for inducing remission
      of active Crohn's disease and for maintaining remission. STUDY SELECTION
      CRITERIA: Randomized controlled trials comparing budesonide to corticosteroids, 5
      ASA products or placebo were included. Trials had to report on the effectiveness
      of treatment (defined as decreasing or maintaining Crohn's Disease Activity
      Index, CDAI, scores < or = 150) or adverse events. DATA ANALYSIS: After assessing
      the validity of study design and independent, duplicate data extraction from
      selected trials, summary relative risks (RR) were calculated for each outcome. A
      test of heterogeneity was also calculated for each outcome using a random effects
      model. RESULTS: Budesonide was more likely to induce remission than placebo
      (RR=1.82, 95% CI: 1.15-2.88) or 5-ASA (RR=1.73, 95% CI: 1.26-2.39), although only
      one trial compared budesonide to 5-ASA products. Although budesonide induced
      remission less frequently than conventional corticosteroids (RR=0.87, 95% CI:
      0.76-0.995), there was no significant difference between conventional
      corticosteroids and budesonide for inducing remission among patients with a low
      disease activity (initial CDAI=200-300). Budesonide was significantly less likely
      to cause corticosteroid-associated adverse events than conventional
      corticosteroids (RR=0.65, 95% CI: 0.53-0.80). No significant difference in total
      adverse events or corticosteroid-associated adverse events was demonstrated
      between budesonide and 5-ASA or placebo. CONCLUSION: Budesonide is significantly
      more effective than placebo or 5-ASA for inducing remission of active Crohn's
      disease. Although budesonide is 13% less effective for the induction of remission
      in active Crohn's disease than conventional corticosteroids, it is less likely to
      cause corticosteroid-related adverse effects. Budesonide is ineffective in
      maintaining remission.

PMID- 12182752
TI  - Discordance between the degree of osteopenia and the prevalence of spontaneous
      vertebral fractures in Crohn's disease.
AB  - BACKGROUND: A high prevalence of osteoporosis has been noted in Crohn's disease,
      but data about fractures are scarce. METHODS: The relationship between low bone
      mineral density and the prevalence of vertebral fractures was studied in 271
      patients with ileo-caecal Crohn's disease in a large European/Israeli study. One
      hundred and eighty-one currently steroid-free patients with active Crohn's
      disease (98 completely steroid-naive) and 90 steroid-dependent patients with
      inactive or quiescent Crohn's disease were investigated by dual X-ray
      absorptiometry scan of the lumbar spine, a standardized posterior/anterior and
      lateral X-ray of the thoracic and lumbar spine, and an assessment of potential
      risk factors for osteoporosis. RESULTS: Thirty-nine asymptomatic fractures were
      seen in 25 of 179 steroid-free patients (14.0%; 27 wedge, 12 concavity), and 17
      fractures were seen in 13 of 89 steroid-dependent patients (14.6%; 14 wedge,
      three concavity). The prevalence of fractures in steroid-naive patients was
      12.4%. The average bone mineral density, expressed as the T-score, of patients
      with fractures was not significantly different from that of those without
      fractures (-0.759 vs. -0.837; P=0.73); 55% of patients with fractures had a
      normal T-score. The bone mineral density was negatively correlated with lifetime
      steroids, but not with previous bowel resection or current disease activity. The
      fracture rate was not correlated with the bone mineral density (P=0.73) or
      lifetime steroid dose (P=0.83); in women, but not in men, the fracture rate was
      correlated with age (P=0.009). CONCLUSIONS: The lack of correlation between the
      prevalence of fractures on the one hand and the bone mineral density and lifetime
      steroid dose on the other necessitates new hypotheses for the pathogenesis of the
      former.

PMID- 12182753
TI  - Percutaneous ethanol injection vs. resection in patients with small single
      hepatocellular carcinoma: a retrospective case-control study with cost analysis.
AB  - BACKGROUND: Percutaneous ethanol injection and hepatic resection are the most
      widely used curative therapeutic options for patients with compensated liver
      disease and small hepatocellular carcinoma. AIM: To compare percutaneous ethanol
      injection and hepatic resection in a selected group of consecutive French
      patients with a single hepatocellular carcinoma, smaller than or equal to 50 mm,
      in terms of survival, recurrence rate of malignancy and direct costs. METHODS:
      The analysis of two contemporary cohorts of Child-Pugh A or B patients with a
      single hepatocellular carcinoma of < or = 50 mm treated by percutaneous ethanol
      injection (n=55) or hepatic resection (n=50). RESULTS: Long-term survival was not
      significantly different between the two groups when the size of hepatocellular
      carcinoma was less than 30 mm. However, the survival of patients with
      hepatocellular carcinoma larger than 30 mm was higher after hepatic resection
      than after percutaneous ethanol injection (P=0.044). The cumulative direct costs
      were significantly higher in patients treated by hepatic resection than in those
      treated by percutaneous ethanol injection regardless of the tumour size. The
      calculated costs per month of survival in patients treated with percutaneous
      ethanol injection and hepatic resection were 999 vs. 3865 euros, respectively (P
      < 0.001). CONCLUSIONS: Percutaneous ethanol injection is more cost effective than
      hepatic resection in patients with a single hepatocellular carcinoma smaller than
      30 mm. However, in patients with a larger tumour, long-term survival is higher
      after hepatic resection.

PMID- 12182754
TI  - The effect of regular medication on the outcome of paracetamol poisoning.
AB  - BACKGROUND: Patients admitted with paracetamol overdose frequently receive one or
      more types of regular medication that may affect the outcome of the paracetamol
      intoxication. AIM: To describe the use of regular medication in patients with
      paracetamol poisoning and to evaluate its effects on morbidity and mortality.
      METHODS: Seven hundred and thirty-seven consecutive patients admitted with
      paracetamol poisoning were studied and the use of regular medication was
      recorded. The relative risk of hepatic encephalopathy, death or liver
      transplantation, severe hepatic dysfunction and severe hepatocellular injury was
      evaluated by multivariate analysis. RESULTS: Regular medication was received by
      332 patients (45%). Medication with benzodiazepines (105 cases), antidepressants
      (100 cases), neuroleptics (75 cases), paracetamol (58 cases), oral contraceptives
      (51 cases), beta-agonists (40 cases), opioid analgesics (32 cases) and
      anticonvulsants (27 cases) predominated. Regular medication with opioid
      analgesics was associated with a high incidence of hepatic dysfunction (odds
      ratio, 5.39; 95% confidence interval, 1.13-25.8). No significant findings were
      demonstrated for benzodiazepines, antidepressants, neuroleptics, paracetamol,
      oral contraceptives, beta-agonists or anticonvulsants in the multivariate
      analysis. CONCLUSIONS: Regular medication with psychotropic medication,
      analgesics, oral contraceptives, beta-agonists or anticonvulsants was frequent in
      patients admitted with paracetamol poisoning. Medication with opioid analgesics
      was associated with a significantly increased incidence of hepatic dysfunction,
      whereas the other medications did not appear to affect the outcome of the
      paracetamol intoxication.

PMID- 12182755
TI  - Serum bile acids in patients with liver failure supported with a bioartificial
      liver.
AB  - BACKGROUND: Serum bile acids are increased in liver failure, but the composition
      of the bile acid pool in this condition has not been studied in detail. This
      information is of interest because of dihydroxy bile acid toxicity. METHODS: We
      measured serum bile acids by gas chromatography-mass spectrometry in 13 patients
      with fulminant liver failure and five patients with acute-on-chronic liver
      failure. Furthermore, serum bile acids were analysed in the same patients after 6
      h of treatment with a bioartificial liver, consisting of a hollow-fibre cartridge
      with microcarrier-attached porcine hepatocytes and a charcoal column. RESULTS:
      Pre-bioartificial liver serum bile acids demonstrated a high dihydroxy/trihydroxy
      ratio and were higher in patients with acute-on-chronic liver failure than in
      those with fulminant liver failure (452.8 +/- 98.6 vs. 182.1 +/- 39.7 micro
      mol/L; P < 0.05). Bioartificial liver treatment decreased significantly serum
      bile acids in patients with fulminant liver failure (-38.8%) and acute-on-chronic
      liver failure (-35.8%), with a decreased dihydroxy/trihydroxy ratio. In vitro,
      porcine hepatocytes in the bioreactor cleared most conjugated bile acid species
      from pooled patient plasma. CONCLUSIONS: Acute liver failure is associated with
      very high serum levels of toxic bile acids that could contribute to the
      pathogenesis of the syndrome. Bioartificial liver treatment reduces both serum
      bile acid concentrations and the hydrophobicity of the bile acid pool.

PMID- 12182756
TI  - Non-transferrin-bound iron in untreated and ribavirin-treated chronic hepatitis C
      patients.
AB  - BACKGROUND: In patients with chronic hepatitis C, elevations in serum iron
      levels, hepatic iron content and oxidative stress-related molecules have been
      reported. Treatment with ribavirin induces an increase in hepatic iron
      concentration. In situations of iron overload, non-transferrin-bound iron can
      appear. Therefore, we determined non-transferrin-bound iron levels in untreated
      chronic hepatitis C patients and in patients during interferon-ribavirin
      treatment. MATERIALS AND METHODS: In 10 untreated and 19 interferon-ribavirin
      treated chronic hepatitis C patients, we examined non-transferrin-bound iron
      levels by a colorimetric method using nitrilotriacetic acid as a ligand and
      sodium triscarbonatecobalt (III) to block free iron binding sites on transferrin.
      RESULTS: Despite the presence of high serum iron saturation and ferritin levels,
      non-transferrin-bound iron was absent in the majority of hepatitis C virus
      patients (25/29, 86%). There was no difference in non-transferrin-bound iron
      levels between untreated and treated patients. Four patients with high non
      transferrin-bound iron levels were distinguished by higher serum iron levels. In
      two of these patients, hepatocytic iron was present on liver biopsy. CONCLUSIONS:
      In the majority of chronic hepatitis C patients, non-transferrin-bound iron
      levels are normal. Treatment with ribavirin does not induce high non-transferrin
      bound iron levels. Non-transferrin-bound iron levels are only higher than normal
      in hepatitis C patients with higher serum iron levels.

PMID- 12182757
TI  - Octreotide enhances the accelerating effect of erythromycin on gastric emptying
      in healthy subjects.
AB  - BACKGROUND: Erythromycin exhibits gastrokinetic properties through cholinergic
      pathways. Reports regarding the action of octreotide on gastric emptying are
      conflicting. AIM: : To assess: (i) the hypothesis that serotonin receptors are
      involved in the accelerating effect of erythromycin on gastric emptying; and (ii)
      any modification of the gastrokinetic action of erythromycin induced by
      octreotide. SUBJECTS AND METHODS: Gastric emptying of a standard meal was
      estimated in 20 healthy subjects by scintigraphy on three different occasions in
      a double-blind, placebo-controlled manner and in random order: (i) after placebo;
      (ii) after 200 mg of intravenous erythromycin; and (iii) after 200 mg of
      intravenous erythromycin following pre-treatment with either 4 mg of intravenous
      ondansetron (10 subjects) or 50 micro g octreotide. RESULTS: Erythromycin
      significantly accelerated gastric emptying in all subjects by abolishing the lag
      phase. Pre-treatment with ondansetron abolished the accelerating effect of
      erythromycin by restoring the emptying times to placebo levels. Octreotide
      significantly enhanced the accelerating effect of erythromycin by reducing both
      the lag and post-lag phases of gastric emptying. CONCLUSIONS: Serotonin receptors
      are involved in the accelerating effect of erythromycin on gastric emptying. This
      effect seems to be enhanced by pre-treatment with octreotide, possibly as a
      result of the modification of the gastrointestinal hormonal environment.

PMID- 12182758
TI  - Magnesium chloride slows gastric emptying, but does not affect digestive
      functions.
AB  - BACKGROUND: An inverse relationship has been established between serum magnesium
      and serum lipid levels. By means of breath tests, we tested the hypothesis that
      magnesium inhibits intraluminal lipid digestion and subsequently causes changes
      in lipid metabolism. We also investigated the influence of the administration of
      magnesium chloride on protein digestion and gastric emptying. METHODS: Five
      healthy volunteers performed simultaneous breath tests for gastric emptying and
      intraluminal lipid digestion, and six others for gastric emptying and protein
      digestion. Each test was performed in basal conditions and after the intake of
      800 mg of magnesium chloride dissolved in water. Breath samples were taken at
      regular time intervals and analysed for 13CO2 and 14CO2 enrichment in order to
      calculate gastric emptying and lipid and protein digestion rates. RESULTS: The
      oral administration of a single dose of magnesium chloride resulted in a
      diminished rate of intraluminal lipid and protein digestion. The most pronounced
      effect of magnesium chloride, however, was a decreased gastric emptying rate of
      both test meals. After correction for gastric emptying, no differences were noted
      in intraluminal lipid or protein digestion. Therefore, the lower lipid levels
      noted after magnesium supplementation are unlikely to be the result of altered
      lipid assimilation. CONCLUSION: Magnesium chloride slows gastric emptying but
      does not influence lipid digestion.

PMID- 12182759
TI  - Mechanistic distinctions between agrin and laminin-1 induced aggregation of
      acetylcholine receptors.
AB  - BACKGROUND: One of the earliest steps in synaptogenesis at the neuromuscular
      junction is the aggregation of nicotinic acetylcholine receptors at the
      postsynaptic membrane. This study presents quantitative analyses of receptor and
      alpha-Dystroglycan aggregation in response to agrin and laminin-1, alone or in
      combination. RESULTS: Both laminin and agrin increased overall expression of
      receptors on the plasma membrane. Following a 24 hour exposure, agrin increased
      the number of receptor aggregates but did not affect the number of alpha
      Dystroglycan aggregates, while the reverse was true of laminin-1. Laminin also
      increased receptor concentration within aggregates, while agrin had no such
      effect. Finally, the spatial distribution of aggregates was indistinguishable
      from random in the case of laminin, while agrin induced aggregates were closer
      together than predicted by a random model. CONCLUSIONS: Agrin and laminin-1 both
      increase acetylcholine receptor aggregate size after 24 hours, but several lines
      of evidence indicate that this is achieved via different mechanisms. Agrin and
      laminin had different effects on the number and density of receptor and alpha
      Dystroglycan aggregates. Moreover the random distribution of laminin induced (as
      opposed to agrin induced) receptor aggregates suggests that the former may
      influence aggregate size by simple mass action effects due to increased receptor
      expression.

PMID- 12182760
TI  - PKQuest: a general physiologically based pharmacokinetic model. Introduction and
      application to propranolol.
AB  - BACKGROUND: A "physiologically based pharmacokinetic" (PBPK) approach uses a
      realistic model of the animal to describe the pharmacokinetics. Previous PBPKs
      have been designed for specific solutes, required specification of a large number
      of parameters and have not been designed for general use. METHODS: This new PBPK
      program (PKQuest) includes a "Standardhuman" and "Standardrat" data set so that
      the user input is minimized. It has a simple user interface, graphical output and
      many new features: 1) An option that uses the measured plasma concentrations to
      solve for the time course of the gastrointestinal, intramuscular, intraperotineal
      or skin absorption and systemic availability of a drug - for a general non-linear
      system. 2) Capillary permeability limitation defined in terms of the permeability
      surface area products. 4) Saturable plasma and tissue protein binding. 5) A lung
      model that includes perfusion-ventilation mismatch. 6) A general optimization
      routine using either a global (simulated annealing) or local (Powell)
      minimization applicable to all model parameters. RESULTS: PKQuest was applied to
      measurements of human propranolol pharmacokinetics and intestinal absorption. A
      meal has two effects: 1) increases portal blood flow by 50%; and 2) decreases
      liver metabolism by 20%. There is a significant delay in the oval propranolol
      absorption in fasting subjects that is absent in fed subjects. The oral
      absorption of the long acting form of propranolol continues for a period of more
      than 24 hours. CONCLUSIONS: PKQuest provides a new general purpose, easy to use,
      freely distributed www.pkquest.com and physiologically rigorous PBPK software
      routine.

PMID- 12182761
TI  - PKQuest: measurement of intestinal absorption and first pass metabolism -
      application to human ethanol pharmacokinetics.
AB  - BACKGROUND: PKQuest, a new physiologically based pharmacokinetic (PBPK) program,
      is applied to human ethanol data. The classical definition of first pass
      metabolism (FPM) based on the differences in the area under the curve (AUC) for
      identical intravenous and oral doses is invalid if the metabolism is non-linear
      (e.g. ethanol). Uncertainties in the measurement of FPM have led to controversy
      about the magnitude of gastric alcohol metabolism. PKQuest implements a new,
      rigorous definition of FPM based on finding the equivalent intravenous input
      function that would produce a blood time course identical to that observed for
      the oral intake. This input function equals the peripheral availability (PA) and
      the FPM is defined by: FPM = Total oral dose - PA. PKQuest also provides a
      quantitative measurement of the time course of intestinal absorption. METHODS:
      PKQuest was applied to previously published ethanol pharmacokinetic data.
      RESULTS: The rate of ethanol absorption is primarily limited by the rate of
      gastric emptying. For oral ethanol with a meal: absorption is slow (Tilde; 3
      hours) and the fractional PKQuest FPM was 36% (0.15 gm/Kg dose) and 7% (0.3
      gm/Kg). In contrast, fasting oral ethanol absorption is fast (Tilde; 50 minutes)
      and FPM is small. CONCLUSIONS: The standard AUC and one compartment methods
      significantly overestimate the FPM. Gastric ethanol metabolism is not
      significant. Ingestion of a coincident meal with the ethanol can reduce the peak
      blood level by about 4 fold at low doses. PKQuest and all the examples are freely
      available on the web at www.pkquest.com.

PMID- 12182762
TI  - Drug-induced and postnatal hypothyroidism impairs the accumulation of
      diacylglycerol in liver and liver cell plasma membranes.
AB  - BACKGROUND: Thyroid hormones are well known modulators of signal transduction.
      The effect of hyper- and hypo-thyroidism on diacylglycerol/protein kinase C
      (DAG/PKC) signaling in cardiomiocytes has been determined. Triiodothyronine (T3)
      has been shown to prevent the alpha1-adrenoreceptor-mediated activation of PKC
      but does not alter the stimulation of enzyme and hepatic metabolism by phorbol
      ethers. It has been suggested that the elevation of endogenous DAG in senescent
      or hypothyroid cells changes the PKC-dependent response of cells to phorbol
      esters and hormones. In the present study, was examined the formation of DAG and
      activation of PKC in liver cells from rats of different thyroid status. RESULTS:
      The results obtained provide the first demonstration of DAG accumulation in liver
      and cell plasma membranes at age- and drug-dependent thyroid gland malfunction.
      The experiments were performed in either the [14C]CH3COOH-labeled rat liver,
      liver slices or hepatocytes labeled by [14C] oleic acid and [3H]arachidonic acid
      or [14C]palmitic acid as well as in the isolated liver cell plasma membranes of
      90- and 720-day-old rats of different thyroid status. The decrease of T4 and T3
      levels in blood serum of 720-day-old rats and mercazolil-treated animals was
      associated with increases of both the DAG mass in liver and liver cell plasma
      membranes and newly synthesized [14C]DAG level in liver and isolated hepatocytes.
      Hypothyroidism decreased PKC activity in both membrane and cytosol as well as
      phospholipid and triacylglycerol synthesis in liver. These hypothyroidism effects
      were restored in liver by injection of T4. T4 administration to the intact
      animals of different ages decreased the DAG level in liver and isolated plasma
      membranes and the content of newly synthesized DAG in liver. The reduction of DAG
      level in liver was not associated with increasing free fatty acid level. DAG
      labeling ratio 14C/3H in liver slices of rats of different thyroid state sharply
      differed from PL. DAG was relatively enriched in [14C]oleic acid whereas PL were
      enriched in [3H]arachidonic acid. CONCLUSIONS: The above data have indicated that
      thyroid hormones are important physiological modulators of DAG level in rat liver
      and cell plasma membranes. Age- and drug-induced malfunction of thyroid gland
      resulted in a prominent decrease of glycerolipid synthesis which may promote DAG
      accumulation in liver.

PMID- 12182763
TI  - Identification of bacteria in drinking and purified water during the monitoring
      of a typical water purification system.
AB  - BACKGROUND: A typical purification system that provides purified water which
      meets ionic and organic chemical standards, must be protected from microbial
      proliferation to minimize cross-contamination for use in cleaning and
      preparations in pharmaceutical industries and in health environments.
      METHODOLOGY: Samples of water were taken directly from the public distribution
      water tank at twelve different stages of a typical purification system were
      analyzed for the identification of isolated bacteria. Two miniature kits were
      used: (i) identification system (api 20 NE, Bio-Merieux) for non-enteric and non
      fermenting gram-negative rods; and (ii) identification system (BBL crystal,
      Becton and Dickson) for enteric and non-fermenting gram-negative rods. The
      efficiency of the chemical sanitizers used in the stages of the system, over the
      isolated and identified bacteria in the sampling water, was evaluated by the
      minimum inhibitory concentration (MIC) method. RESULTS: The 78 isolated colonies
      were identified as the following bacteria genera: Pseudomonas, Flavobacterium and
      Acinetobacter. According to the miniature kits used in the identification, there
      was a prevalence of isolation of P. aeruginosa 32.05%, P. picketti (Ralstonia
      picketti) 23.08%, P. vesiculares 12.82%,P. diminuta 11.54%, F. aureum 6.42%, P.
      fluorescens 5.13%, A. lwoffi 2.56%, P. putida 2.56%, P. alcaligenes 1.28%, P.
      paucimobilis 1.28%, and F. multivorum 1.28%. CONCLUSIONS: We found that research
      was required for the identification of gram-negative non-fermenting bacteria,
      which were isolated from drinking water and water purification systems, since
      Pseudomonas genera represents opportunistic pathogens which disperse and adhere
      easily to surfaces, forming a biofilm which interferes with the cleaning and
      disinfection procedures in hospital and industrial environments.

PMID- 12182764
TI  - PKQuest: volatile solutes - application to enflurane, nitrous oxide, halothane,
      methoxyflurane and toluene pharmacokinetics.
AB  - BACKGROUND: The application of physiologically based pharmacokinetic models
      (PBPK) to human studies has been limited by the lack of the detailed organ
      information that is required for this analysis. PKQuest is a new generic PBPK
      that is designed to avoid this problem by using a set of "standard human" default
      parameters that are applicable to most solutes. RESULTS: PKQuest is used to model
      the human pharmacokinetics of the volatile solutes. A "standard human" value for
      the lipid content of the blood and each organ (klip) was chosen. This set of klip
      and the oil/water partition coefficient then specifies the organ/blood partition
      for each organ. Using this approach, the pharmacokinetics of inert volatile
      solute is completely specified by just 2 parameters: the water/air and oil/water
      partition coefficients. The model predictions of PKQuest were in good agreement
      with the experimental data for the inert solutes enflurane and nitrous oxide and
      the metabolized solutes halothane and toluene. METHODS: The experimental data
      that was modeled was taken from previous publications. CONCLUSIONS: This approach
      greatly increases the predictive power of the PBPK. For inert volatile solutes
      the pharmacokinetics are determined just from the water/air and oil/water
      partition coefficient. Methoxyflurane cannot be modeled by this PBPK because the
      arterial and end tidal partial pressures are not equal (as assumed in the PBPK).
      This inequality results from the "washin-washout" artifact in the large airways
      that is established for solutes with large water/air partition
      coefficients.PKQuest and the worked examples are available on the web
      www.pkquest.com.

PMID- 12182766
TI  - The neurosurgeon in sport: awareness of the risks of heatstroke and dietary
      supplements.
AB  - THE SCIENCE OF fluid replacement in athletic training, particularly with regard
      to American football players, has advanced during the past 3 decades. This
      advance has resulted in substantial decreases in heatstroke-related deaths during
      summer training sessions. Recent trends in football heatstroke fatalities toward
      significant increases may, in part, be attributable to or aggravated by the use
      of dietary supplements. Credible scientific evidence has been found that
      amphetamine derivatives and the ergonomic aid creatine may contribute to
      subclinical dehydration and heatstroke in selected individuals. Caution is urged
      in the education and evaluation of football players who train during the hot
      summer months.

PMID- 12182765
TI  - Chronic garlic administration protects rat heart against oxidative stress induced
      by ischemic reperfusion injury.
AB  - BACKGROUND: Oxidative stress plays a major role in the biochemical and
      pathological changes associated with myocardial ischemic-reperfusion injury
      (IRI). The need to identify agents with a potential for preventing such damage
      has assumed great importance. Chronic oral administration of raw garlic has been
      previously reported to augment myocardial endogenous antioxidants. In the present
      study, the effect of chronic oral administration of raw garlic homogenate on
      oxidative stress induced by ischemic-reperfusion injury in isolated rat heart was
      investigated. RESULTS: Raw garlic homogenate (125, 250 and 500 mg/kg once daily
      for 30 days) was administered orally in Wistar albino rats. Thereafter, hearts
      were isolated and subjected to IRI (9 min. of global ischemia, followed by 12 min
      of reperfusion; perfusion with K-H buffer solution; 37 degrees C, 60 mm Hg.).
      Significant myocyte injury and rise in myocardial TBARS along with reduction in
      myocardial SOD, catalase, GSH and GPx were observed following IRI. Depletion of
      myocardial endogenous antioxidants and rise in TBARS were significantly less in
      the garlic-treated rat hearts. Oxidative stress induced cellular damage as
      indicated by ultrastructural changes, like disruption of myofilament, Z-band
      architecture along with mitochondrial changes were significantly less.
      CONCLUSIONS: The study strongly suggests that chronic garlic administration
      prevents oxidative stress and associated ultrastructural changes, induced by
      myocardial ischemic-reperfusion injury.

PMID- 12182767
TI  - Brain oxygenation and energy metabolism: part I-biological function and
      pathophysiology.
AB  - CONTINUOUS OXYGEN DELIVERY and CO(2) clearance are paramount in the maintenance
      of normal brain function and tissue integrity. Under normal conditions, aerobic
      metabolism is the major source of energy in the brain, but this system may be
      compromised by the interruption of substrate delivery and disturbances in
      cerebral metabolism. These disruptions are major factors contributing to ischemic
      and hypoxic brain damage resulting from traumatic brain injury, stroke, and
      subarachnoid hemorrhage. There is evidence that mitochondrial function also is
      reduced after injury. Furthermore, early impairment of cerebral blood flow in
      patients with severe injury correlates with poor tissue oxygenation and may be an
      important parameter in secondary damage. Recent advances in brain tissue
      monitoring in the intensive care unit and operating room have made it possible to
      continuously measure tissue oxygen tension and temperature, as well as certain
      aspects of brain metabolism and neurochemistry. Therefore, it is important to
      understand the physiological process and the pathophysiology produced by these
      events. This is Part I of a two-part review that analyzes the physiology of
      cerebral oxygenation and metabolism as well as some of the pathological
      mechanisms involved in ischemic and traumatic brain injuries. Brain tissue
      monitoring techniques will be examined in the second article of this two-part
      series. To understand cerebral oxygenation, it is important to understand
      cerebral blood flow, energy production, ischemia, acidosis, generation of
      reactive oxygen species, and mitochondrial failure. These issues provide the
      basis of knowledge regarding brain bioenergetics and are important topics to
      understand when developing new approaches to patient care.

PMID- 12182768
TI  - Results of multimodality treatment for 141 patients with brain arteriovenous
      malformations and seizures: factors associated with seizure incidence and seizure
      outcomes.
AB  - OBJECTIVE: Previous reports of seizure outcomes after arteriovenous malformation
      (AVM) treatment have involved single-treatment modality (surgery, radiosurgery,
      or embolization) series. Such series reflect only selected lesions, of certain
      sizes, locations, and other clinical and anatomic characteristics, that are
      amenable to the single therapy, limiting the analysis of those factors. We report
      the results of AVM treatment using a multimodality approach that we think
      encompasses a broader spectrum of treatable brain AVMs. We tested for factors
      associated with seizure presentation and seizure outcomes. METHODS: Between 1991
      and 1999, the multidisciplinary neurovascular unit at Massachusetts General
      Hospital treated 424 patients with brain AVMs. Treatment consisted of surgical
      resection, radiosurgery, or embolization, either alone or in combination. One
      hundred forty-one patients (33%) experienced seizures before treatment. We
      studied the following factors: sex, age, AVM size, AVM location, occurrence of
      intracranial hemorrhage, seizure type, duration of seizure history, treatment
      modality, and AVM obliteration. We tested for statistical associations between
      these factors and seizure presentation and outcomes. Clinical follow-up
      monitoring was via mailed questionnaires. RESULTS: When we compared the 141
      patients with seizures with the 283 patients who did not experience seizures
      (total of 424 patients), male sex, age of less than 65 years, AVM size of more
      than 3 cm, and temporal lobe AVM location were statistically associated with
      seizures (P < 0.01, P < 0.05, P < 0.0001, and P < 0.01, respectively). Posterior
      fossa and deep locations were statistically associated with no seizures (P <
      0.0001). One hundred ten (78%) of the 141 patients who experienced seizures
      before treatment responded to the mailed questionnaires, with a mean follow-up
      period of 2.9 years. A detailed comparison of responders and nonresponders
      demonstrated no statistically significant differences in pertinent
      characteristics. As determined with the Engel Seizure Outcome Scale, there were
      73 (66%) Class I (free of disabling seizures), 11 (10%) Class II (rare disabling
      seizures), 1 (0.9%) Class III (worthwhile improvement), and 22 (20%) Class IV (no
      worthwhile improvement) outcomes. Three patients died during the follow-up
      period. We tested for factors associated with Engel Class I outcomes. Sex, age,
      and AVM size were not associated with Class I outcomes. Short seizure history,
      association of seizures with intracranial hemorrhage, generalized tonicoclonic
      seizure type, deep and posterior fossa AVM locations, surgical resection, and
      complete AVM obliteration were statistically associated with Class I outcomes (P
      < 0.0001, P < 0.05, P < 0.05, P < 0.05, P < 0.001, and P < 0.001, respectively).
      When only completely obliterated AVMs were considered, there were no
      statistically significant differences between surgery, radiosurgery, and
      embolization. CONCLUSION: Certain factors, as identified in an analysis of a wide
      spectrum of treatable brain AVMs, can facilitate predictions of the incidence of
      seizure presentation with AVMs, as well as seizure outcomes after multimodality
      treatment.

PMID- 12182770
TI  - Hemodynamic evaluation of basilar and vertebral artery angioplasty.
AB  - OBJECTIVE: The postangioplasty evaluation of a stenotic vessel is often conducted
      by studying serial angiograms to determine the anatomic reduction in stenosis. In
      flow-limiting stenosis, the hemodynamic change that accompanies these anatomic
      changes is of great importance in evaluating the success of the angioplasty. The
      purpose of this article is to demonstrate the usefulness of phase contrast
      magnetic resonance angiography (PCMRA) in evaluating the hemodynamic changes that
      occur after angioplasty of the basilar and vertebral arteries. METHODS: Between
      January 1998 and February 2000, PCMRA was performed for the hemodynamic
      evaluation of 130 patients who presented at our institution. Twenty-six patients
      were evaluated for vertebrobasilar insufficiency, and flow rates of their
      vertebral and basilar arteries were determined. In five patients, angioplasty was
      done on the basilar or vertebral arteries, and PCMRA was performed to determine
      flow rates before and after the procedure. RESULTS: Of the five patients
      undergoing angioplasty, the average percentage of stenosis was 81%. The average
      increase in basilar artery flow rate was 46 ml/min (P < 0.05) after angioplasty.
      Two of these patients are described. One patient demonstrated the comparison of
      flow rates in the vertebral and basilar arteries after angioplasty. The second
      patient showed follow-up flow rates measured after angioplasty and up to 4 months
      later to predict restenosis. CONCLUSION: The use of flow rate data before and
      after angioplasty is helpful not only to evaluate the treatment immediately after
      the procedure but also to evaluate the effectiveness of the treatment during a
      long period. PCMRA provides a noninvasive method for measuring arterial flow
      rates with far-reaching implications in neurosurgery.

PMID- 12182769
TI  - Cerebral perfusion before and after endovascular or surgical treatment of acutely
      ruptured cerebral aneurysms: a 1-year prospective follow-up study.
AB  - OBJECTIVE: To prospectively determine temporal changes in regional cerebral
      perfusion in patients with acutely (<72 h) ruptured cerebral aneurysms treated
      either endovascularly or surgically. METHODS: Cerebral perfusion was measured
      both before and 1 week after treatment by use of a (99m)Tc-labeled ethyl-cysteine
      dimer and single-photon emission computed tomographic (SPECT) studies in 46 of 81
      consecutive patients included in a prospective randomized study of early
      treatment of ruptured aneurysms. In addition to visual analysis of the SPECT
      images, corticocerebellar perfusion ratios were calculated for seven predefined
      bilateral regions. Late ischemic deficits were evaluated after 12 months by
      magnetic resonance imaging of the brain. RESULTS: Acute perfusion deficits were
      commonly seen before treatment. In the visual comparison between the first and
      second SPECT studies, the number of new or enlarged deficits (P = 0.006) and
      deficits that expanded from unilateral to bilateral (P = 0.020) significantly
      increased in the surgical group but not in the endovascular group. In the second
      SPECT study, surgical patients had decreased corticocerebellar perfusion ratios
      in the right frontobasal cortex (P = 0.012) compared with the endovascular
      patients, and in the ipsilateral frontobasal cortex (P = 0.002) and ipsilateral
      temporal apex (P = 0.002) compared with the contralateral side of the ruptured
      aneurysm. The 12-month magnetic resonance imaging of the brain revealed no
      significant difference in the number of ischemic deficits between the
      endovascular and surgical groups. CONCLUSION: Disturbances in cerebral perfusion
      both before and after treatment are common. Although no major differences in the
      findings were detected between patients treated with either clips or coils,
      progression of perfusion deficits was more common in the surgical group. However,
      the 12-month magnetic resonance imaging of the brain revealed equal numbers of
      ischemic deficits in the treatment groups.

PMID- 12182771
TI  - Transradial cerebral angiography: an alternative route.
AB  - INTRODUCTION: The transradial approach has been well described for arteriography
      of the coronary vessels. To assess the safety and success rate of the transradial
      approach for three-vessel or four-vessel diagnostic cerebral arteriography, we
      reviewed the experience at our institution and compared our complication rates
      with those found in the literature for transfemoral cerebral angiography and
      transradial coronary angiography. METHODS: We reviewed the electronic medical
      records of 129 consecutive patients in whom 132 cerebral angiographic studies
      were performed by use of a transradial approach between December 1999 and June
      2001. A total of 54 selective catheterizations were performed, of which 39 were
      of the vertebral artery, 11 of the internal carotid artery, and 4 of the external
      carotid artery. Records were reviewed for periprocedural and delayed
      complications, indications for diagnostic angiography, and requirement of
      conversion to a femoral approach. Records were reviewed prospectively for the
      first 55 procedures and retrospectively for the next 77 procedures. RESULTS: The
      mean time to initial clinical follow-up was 1.5 months (median, 0.5 mo). The
      combined rate of periprocedural and delayed complications was 9%, and there were
      no major complications. Minor periprocedural complications included transient
      radial artery spasm (four patients), failure to access the brachial artery (two
      patients), severe pain (one patient), skin desquamation (one patient), and
      hematoma (one patient). There were no major complications. At the time of follow
      up evaluation, these patients were without deficits related to cannulation of the
      radial artery. CONCLUSION: The transradial approach for cerebral angiography is a
      safe alternative to the transfemoral route. After transradial cerebral
      angiography, patients require a shorter observation period and are not restricted
      to bed rest. As technological developments generate smaller, more pliable
      endovascular surgical devices, future endovascular surgery may be performed
      transradially.

PMID- 12182773
TI  - Prospective feasibility study of outpatient stereotactic brain lesion biopsy.
AB  - OBJECTIVE: To assess the safety and feasibility of performing computed tomography
      guided stereotactic brain lesion biopsy as an outpatient day-surgery procedure.
      METHODS: In late 1996, a prospective trial of outpatient stereotactic biopsies
      was initiated. The protocol consists of preadmission education of the patient,
      computed tomography-guided biopsy with local anesthesia (using a Brown-Roberts
      Wells or Cosman-Roberts-Wells frame), postoperative observation in the
      postanesthetic care unit for 2 hours and in the day surgery unit for 2 hours, and
      then discharge home 4 hours after the procedure. RESULTS: Seventy-six patients
      constituted the intent-to-treat group, of whom two were not discharged on the
      same day (97.4% success rate). The two patients underwent inpatient admission
      because one required intravenous antibiotic treatment of a brain abscess and the
      other had a hard lesion in the brainstem that precluded biopsy needle
      penetration; admission for further investigation of the lesion was elected. Two
      patients experienced complications (2.6%), i.e., one small area of
      intraventricular hemorrhage that produced only a mild headache and one case of
      mild worsening of preexisting leg weakness, with negative computed tomographic
      results. CONCLUSION: Discharging patients home after 4 hours of observation after
      stereotactic biopsies seems to be a safe, well-tolerated practice. In this
      series, there was no major morbidity and no patient was disadvantaged by
      participating in this protocol. This approach would be expected to result in
      health care resource and cost savings, with a potential increase in patient
      satisfaction because of shorter hospital stays.

PMID- 12182772
TI  - The Brain Tumor Cooperative Group NIH Trial 87-01: a randomized comparison of
      surgery, external radiotherapy, and carmustine versus surgery, interstitial
      radiotherapy boost, external radiation therapy, and carmustine.
AB  - OBJECTIVE: The objective of the Brain Tumor Cooperative Group NIH Trial 87-01
      trial was to investigate the effect of additional implanted radiation therapy in
      newly diagnosed patients with pathologically confirmed malignant gliomas.
      METHODS: The study involved a randomized comparison of surgery, external beam
      radiotherapy, and carmustine (BCNU) versus surgery, external beam therapy,
      interstitial radiotherapy boost, and BCNU in newly diagnosed malignant gliomas.
      (125)I was chosen as best suited for this effort because it allowed
      preimplantation planning and postimplantation quality assurance review. Two
      hundred ninety-nine patients met the eligibility criteria and were randomized
      into the two arms of the study between December 1987 and April 1994. Follow-up
      continued for an additional 3 years. Twenty-nine patients were identified as
      having committed protocol violations and were excluded, resulting in 270 subjects
      in the Valid Study Group. One hundred thirty-seven patients received external
      beam radiation and BCNU, and 133 underwent the (125)I implantation plus external
      beam radiation and BCNU therapy. RESULTS: The overall median survival for the
      Valid Study Group was 64.3 weeks. The median survival for patients receiving
      additional therapy of (125)I was 68.1 weeks, and median survival for those
      receiving only external beam radiation and BCNU was 58.8 weeks. The cumulative
      proportion surviving between the two treatment groups was not statistically
      significantly different (log-rank test, P = 0.101). As in other studies in the
      literature, age, Karnofsky score, and pathology were predictors of mortality.
      Additional analyses incorporating an adjustment for these prognostic variables,
      either in a stratified analysis or Cox proportional hazards model, did not result
      in statistically significant differences in the cumulative proportion of patients
      surviving between the two treatment groups. CONCLUSION: We conclude that there is
      no long-term survival advantage of increased radiation dose with (125)I seeds in
      newly diagnosed glioma patients.

PMID- 12182774
TI  - Latency between symptom onset and diagnosis of pediatric brain tumors: an Eastern
      Canadian geographic study.
AB  - OBJECTIVE: Tumors of the central nervous system are now thought to be the most
      common form of childhood malignancies. Previous studies suggested that delays
      might exist between symptom onset and the diagnosis of pediatric brain tumors. In
      the Maritime Provinces of Canada (New Brunswick, Nova Scotia, and Prince Edward
      Island), there are only two pediatric neurosurgical centers; therefore, the
      Maritime Provinces are ideal for study of the epidemiological features of
      pediatric brain tumors. The aim of this study was to examine the incidence rates
      of pediatric brain tumors in eastern Canada, as well as factors important in
      their diagnosis. METHODS: We collected data on 104 cases during a 6-year period
      (1995-2000), both prospectively and retrospectively, for the Maritime pediatric
      neuro-oncology database. All < or =17-year-old patients in the Maritime Provinces
      with pediatric brain tumors were treated in one of two neurosurgical centers (St.
      John, New Brunswick, or Halifax, Nova Scotia). RESULTS: The incidence rate for
      pediatric brain tumors was 4.28/100,000 child-yr. Tumors were more common among
      male patients and involved the infratentorial compartment in 65% of the total
      cases. The two most common types of tumors were astrocytomas (37%) and
      medulloblastomas (21%). The mean time to diagnosis was 7.3 months (95% confidence
      interval [CI], 4.99-9.67 mo), and only 41% of our cases were correctly diagnosed
      within three visits to various physicians. Tumors located in the brainstem
      required significantly longer times for diagnosis, compared with those located
      elsewhere (mean, 11.76 mo [95% CI, 3.13-20.39 mo] versus 6.57 mo [95% CI, 4.20
      8.95 mo]; P = 0.014). Medulloblastomas as a group exhibited significantly shorter
      diagnostic times, compared with other pathological subtypes (mean, 3.78 mo [95%
      CI, 1.97-5.59 mo] versus 8.35 mo [95% CI, 5.40-11.3 mo]; P = 0.006). CONCLUSION:
      The incidence rates for pediatric brain tumors in the Maritime Provinces are
      similar to those of other reported series. The correct diagnosis of pediatric
      brain tumors still generally requires a number of months and frequent visits to
      various physicians. The majority of pediatric brainstem tumors might no longer be
      of a diffuse malignant nature but might represent more-focal benign lesions.

PMID- 12182775
TI  - Classification of spinal cord arteriovenous shunts: proposal for a reappraisal-
      the Bicetre experience with 155 consecutive patients treated between 1981 and
      1999.
AB  - OBJECTIVE: Spinal cord arteriovenous shunts (SCAVSs) are currently classified
      according to their morphological features. Certain shunts cannot be fully
      integrated into the predetermined categories that are usually described, however.
      Can these classifications be reevaluated on the basis of recent anatomic,
      biological, and genetic advances? METHODS: We reviewed the clinical and
      radiological files for 155 SCAVSs that were treated at Hopital Bicetre between
      1981 and 1999. The lesions were examined with respect to their number (single or
      multiple), their primary architectural type (nidus or fistula), and their
      possible links with associated metameric lesions. RESULTS: All SCAVSs were either
      arteriovenous malformations or fistulae, with the latter being either micro- or
      macrofistulae. All SCAVSs corresponded to three categories, i.e., genetic
      hereditary lesions (macrofistulae and hereditary hemorrhagic telangiectasia),
      genetic nonhereditary lesions (all of which were multiple lesions with metameric
      or myelomeric associations), and single lesions (which could represent incomplete
      presentations of one of the previous groups). Of the SCAVSs in our series, 81%
      were single lesions and 19% were multiple; among these, 59% were true intradural
      shunts with metameric features. Ten cases of Cobb syndrome, three cases of
      Klippel-Trenaunay syndrome, and two cases of Parkes-Weber syndrome, all with
      associated cord lesions, were observed. Nineteen percent of SCAVSs were fistulae;
      23% of those were macrofistulae, of which 83% were related to Rendu-Osler-Weber
      disease. CONCLUSION: It seems legitimate to propose a categorization that takes
      into consideration a primary malformation (nidus or fistula) that evolves with
      time and in which angioarchitectural changes occur. Recognition of the factors
      originally responsible for the shunt (e.g., genetic hereditary or genetic
      nonhereditary) allows a different classification of SCAVSs.

PMID- 12182776
TI  - Spinal cord stimulation electrode design: prospective, randomized, controlled
      trial comparing percutaneous and laminectomy electrodes-part I: technical
      outcomes.
AB  - OBJECTIVE: The clinical use of spinal cord stimulation for treatment of chronic
      intractable pain has been increasingly successful because of recent technical
      improvements, particularly the development of multiple-contact electrodes
      supported by programmable implanted pulse generators. Contemporary electrodes can
      be placed percutaneously in some cases and require a limited laminectomy in other
      cases. METHODS: We performed a prospective, randomized, controlled trial
      comparing two prototypical electrode designs, using a computerized system that
      allows direct patient interaction and quantitative measurements. A series of 24
      patients with chronic lumbosacral pain syndromes first underwent testing with
      percutaneous four-contact electrodes and then underwent implantation, at the same
      spinal level, of one of two different electrode configurations; 12 patients
      received a new percutaneous four-contact electrode of the same design and 12
      received an insulated four-contact array, which was implanted via laminectomy.
      RESULTS: The insulated array performed significantly (P = 0.0005-0.0047) better
      than the temporary percutaneous electrode for the same patients, according to all
      three measures tested (ratings of paresthesia coverage of pain, coverage
      calculated from patient drawings, and amplitudes), at the "usage" amplitude for
      the three standard bipoles examined. The insulated array also performed
      significantly (P = 0.0000-0.026) better than the permanent percutaneous electrode
      in terms of coverage ratings and amplitude requirements. Low back coverage
      ratings were significantly better for the insulated array than for the temporary
      percutaneous electrode, and scaled amplitudes necessary for low back coverage
      were significantly better for the permanent percutaneous electrode than for the
      temporary electrode. In comparison with the percutaneous temporary electrode, at
      subjectively identical stimulation intensities, the permanent insulated array
      required significantly lower amplitude. CONCLUSION: We can immediately infer from
      these technical data that the use of an insulated array, in comparison with a
      percutaneous electrode, would double battery life. Extended follow-up monitoring
      will be required to assess the extent to which the technical advantages we
      observed for the insulated array might be associated with improved clinical
      outcomes.

PMID- 12182777
TI  - Efficacy of prophylactic antibiotic therapy in spinal surgery: a meta-analysis.
AB  - OBJECTIVE: There is considerable variation in practice regarding the use of
      prophylactic antibiotic therapy in spinal operations. To date, individual studies
      have not demonstrated a significant benefit for prophylactic antibiotic therapy
      in spinal operations. METHODS: Systematic database searches for randomized
      prospective trials of prophylactic antibiotic therapy in spinal surgery, general
      neurosurgery, and orthopedic surgery were performed. Random-effects meta-analysis
      and Bayesian meta-regressions of treatment benefits versus baseline infection
      rates and other trial characteristics were performed. RESULTS: Six prospective
      randomized trials or trial subgroups, enrolling 843 patients, were identified,
      i.e., one spinal surgery trial, four general neurosurgery trials, and one general
      orthopedic surgery trial. No individual trial demonstrated a statistically
      significant effect of prophylactic antibiotic therapy for spinal surgery
      patients. Raw pooled infection rates were 2.2% (10 of 451 patients) with
      antibiotics and 5.9% (23 of 392 patients) without antibiotics. Individual trial
      infection rates ranged from 1.2 to 8.5%. The pooled odds ratio was 0.37 (95%
      confidence interval, 0.17-0.78), favoring antibiotic treatment (P < 0.01). There
      was no significant heterogeneity in treatment efficacy among the trials. Bayesian
      meta-regression was used to test whether antibiotics were less effective in
      trials with low baseline infection rates and whether an optimal antibiotic
      regimen could be identified. There was no significant difference in antibiotic
      treatment effects in trials with lower baseline infection rates, in trials using
      antibiotics with gram-negative coverage in addition to gram-positive coverage, or
      in trials using multiple-dose versus single-dose regimens. Nonrandomized studies
      of antibiotic therapy in spinal surgery yielded greater treatment effect
      estimates than did randomized trials, but not significantly so. CONCLUSION:
      Prophylactic antibiotic therapy is beneficial for spinal surgery, even when
      expected infection rates without antibiotic treatment are low.

PMID- 12182778
TI  - Brain operations guided by real-time two-dimensional ultrasound: new
      possibilities as a result of improved image quality.
AB  - OBJECTIVE: In 1995, a project was initiated in Trondheim, Norway, to investigate
      various possibilities for more frequent use of ultrasound in brain surgery. Since
      that time, the quality of ultrasonic images has improved considerably through
      technological adjustment of parameters. The objective of the present study was to
      explore essential clinical parameters required for the successful use of
      ultrasonic guidance in brain surgery. METHODS: During the study period, several
      surgical setups designed to optimize the use of intraoperative real-time two
      dimensional ultrasonic imaging were explored. These included various positions of
      the ultrasound probe in relation to both the operation cavity and the lesion, as
      well as the position of the operation channel in relation to the gravity line.
      RESULTS: All lesions from the latest period (1997-2001; n = 114) were depicted
      well by ultrasound imaging, with the exception of two cases. High image quality
      and direct image guidance of the tool were maintained best throughout the
      operation by imaging through an intact dura and at an angle relative to a
      vertical operation channel. All tumor operations were performed without
      complications, and ultrasound imaging was found to be an important factor in the
      detection of remaining tumor tissue at the conclusion of surgery. For 14 low
      vascular tumors, the operation was guided only by ultrasound imaging. No bleeding
      complications occurred. A method of minimally invasive ultrasound-guided
      evacuation of hematomas was developed. In 19 patients, the method was found to be
      efficient (i.e., >90% of the hematoma was evacuated) and without complications,
      except for one patient who experienced rebleeding. CONCLUSION: With proper
      planning and surgical setup, ultrasound imaging may provide acceptable image
      quality for use in image-guided brain operations.

PMID- 12182779
TI  - Polylactic acid mesh reconstruction of the anterior iliac crest after bone
      harvesting reduces early postoperative pain after anterior cervical fusion
      surgery.
AB  - OBJECTIVE: Autologous iliac crest bone enhances the rate of spinal arthrodesis.
      However, graft site complications are common, with donor site pain being
      particularly troublesome. Reconstruction of the hip defect with an absorbable
      polylactic acid mesh to restore the bony cortical contour has been proposed to
      reduce hip pain. METHODS: Thirty-nine consecutive patients treated by a single
      senior surgeon (BAG) during a 14-month period were studied. All patients had
      cervical spondylosis treated through an anterior approach supplemented with an
      autologous hip graft. Patients with preexisting hip pain were excluded. Pain was
      rated on a scale of 1 to 10 at 1 week and 3 months after surgery via a
      questionnaire. Postoperative pain medication regimens were standardized. RESULTS:
      Thirty patients were available for follow-up, 15 with mesh implantation and 15
      without. Hip pain in the mesh-treated group averaged 4.7 and 1.6 at 1 week and 3
      months, respectively. Hip pain in the standard-treatment group averaged 6.9 and
      2.5 at 1 week and 3 months, respectively. These differences were statistically
      significant (P = 0.004 at 1 wk and 0.055 at 3 mo). Hospital length of stay was
      shorter in the mesh-treated group (2.1 versus 3.2 d, respectively), but this
      difference was not statistically significant. Two patients without mesh treatment
      complained of the cosmetic defect resulting from absent bone, and three had
      temporary difficulty with hip eversion or flexion. Two patients in the mesh
      treated group developed seromas, which were treated conservatively. CONCLUSION:
      Reconstruction of the iliac crest reduces early postoperative pain. Other
      potential benefits may include shorter hospitalizations and a reduced incidence
      of hip weakness; however, careful attention to wound closure is necessary to
      prevent seroma formation.

PMID- 12182780
TI  - Use of the telescopic plate spacer in treatment of cervical and cervicothoracic
      spine tumors.
AB  - OBJECTIVE: We investigated the mechanical and in vivo properties of a novel
      device, called the telescopic plate spacer (TPS), designed to promote restoration
      of height, alignment, and stability after cervical corpectomy for tumor. METHODS:
      The device first underwent mechanical testing. Comparisons were made with a
      commercially available anterior cervical plate. A caprine study was then
      performed. Twelve goats underwent a cervical corpectomy and placement of either a
      TPS filled with autograft or a plate and autograft. The animals were killed at 28
      weeks and assessed for fusion. A prospective human study was then conducted.
      Fifteen patients with cervical or cervicothoracic tumors underwent corpectomy and
      placement of allograft-filled TPS. End points included pain scores and
      radiographic assessment of vertebral height, alignment, and stability. RESULTS:
      In the mechanical study, the TPS outperformed the anterior cervical plate in all
      modalities except for torsion stiffness and tension-bending failure load. The
      caprine study demonstrated fusion in six of six cases at 28 weeks in the TPS
      group, compared with four of six cases in the plate and autograft group. In the
      human study, patients (n = 15) were stabilized with the TPS after corpectomy
      (range, 1-3 levels; average, 1.7 levels). There were no failures of
      instrumentation or neurological deterioration. Stability was achieved in all
      patients, with an average follow-up of 9 months. Durable improvements in pain
      scores (P = 0.001), vertebral height (P = 0.002), and reduction of kyphosis (P =
      0.046) were achieved. CONCLUSION: The TPS can be used to restore height,
      alignment, and stability after corpectomy.

PMID- 12182781
TI  - Is the root entry/exit zone important in microvascular compression syndromes?
AB  - OBJECTIVE: Microvascular compression syndromes such as trigeminal neuralgia,
      hemifacial spasm, and disabling positional vertigo involve an artery or vein
      compressing a cranial nerve. A cranial nerve is composed of a central nervous
      system (CNS) segment and a peripheral nervous system (PNS) segment separated by
      the root entry/exit zone (REZ). Although vascular compression can occur at any
      point along the cranial nerve, it has been generally assumed that only vascular
      contact at the REZ of the affected cranial nerve can cause symptoms. On the basis
      of personal surgical experience, we propose that vascular compression of the CNS
      segment alone causes symptoms. This has important repercussions for the future
      diagnosis and treatment of microvascular compression syndromes, especially the
      cochleovestibular compression syndrome. METHODS: For the anatomic study, four
      autopsy specimens and one surgical biopsy specimen of the vestibulocochlear nerve
      were microscopically and ultramicroscopically analyzed for structural differences
      between the CNS and PNS segments. For the clinical study, five patients with the
      clinical picture of cochleovestibular compression syndrome were treated by
      microsurgical decompression at the level of the CNS segment and not the REZ. One
      patient underwent reoperation for recurrent symptoms 4 years later, and a 4-mm
      vestibular neurectomy was performed at that stage. We performed an
      epidemiological analysis to demonstrate that the known incidences of trigeminal
      neuralgia, hemifacial spasm, and glossopharyngeal neuralgia are related to the
      length of their respective CNS segments. RESULTS: Histological differences
      between the PNS and CNS segments suggest that the PNS segment is more resistant
      to compression. This was confirmed by neurophysiological data from intraoperative
      monitoring in posterior fossa surgery and experimental studies. We found a clear
      epidemiological correlation between the length of the CNS segment, which differed
      among cranial nerves, and the incidence of the microvascular compression
      syndrome. Successful decompression of the CNS segment in patients without
      compression at the REZ of the vestibulocochlear nerve for disabling positional
      vertigo provides clinical support for this hypothesis. CONCLUSION: The evidence
      we present supports the hypothesis that vascular compression syndromes arise from
      vascular contact along the CNS segment of the cranial nerves.

PMID- 12182782
TI  - Pituitary surgery: transsphenoidal approach.
AB  - THE TRANSSPHENOIDAL APPROACH for sellar tumors has evolved significantly since it
      was described initially during the first decade of the 20th century. The approach
      currently incorporates technological advancements and refinements in patient
      selection, operative technique, and postoperative care. Although many of these
      innovations are considered indispensable, the operative technique, as performed
      by contemporary neurosurgeons, is not standardized. This variability is a
      reflection of surgeon's preference, the lessons of experience, and the bias
      inherent in neurosurgical training. The methods and preferences described herein
      embody the distillation of an experience gained from 3900 transsphenoidal
      operations.

PMID- 12182784
TI  - In vivo assessment of calcium alginate gel for endovascular embolization of a
      cerebral arteriovenous malformation model using the Swine rete mirabile.
AB  - OBJECTIVE: We sought to assess the stability of calcium alginate as an embolic
      agent in an animal model of a cerebral arteriovenous malformation (AVM). Swine
      cerebral AVM models were used to test the injectability, radiographic
      visualization, mechanical stability, and biocompatibility of calcium alginate as
      an occlusive agent. METHODS: The swine cerebral AVM model included a carotid-to
      jugular anastomosis to increase flow to the rete mirabile (RM), thereby
      simulating the pressure gradient and shunted blood flow of an AVM. Alginate and
      the reactive component, calcium chloride, were injected from double-lumen
      microcatheters to form a complete RM occlusion in the "acute swine" AVM model and
      a partial occlusion in a "survival swine" model. RESULTS: Angiographic and
      histological results verified complete occlusion of the left RM in acute animals
      when alginate was injected in stages. Partial RM occlusion in the survival
      animals blocked blood flow to the inferior portion of the RM but left flow open
      to the superior portion of the RM and the circle of Willis. One-week survival
      results showed that the alginate remained a stable occlusive material.
      Histological results showed a minor bioactive response and encapsulation of the
      alginate polymer, thereby increasing the stability and effective occlusion of the
      embolization material. CONCLUSION: Calcium alginate proved to be an effective
      endovascular occlusion material that blocked blood flow to the swine RM. The
      swine AVM models provided assessment of alginate injectability and effective
      occlusion and provided initial in vivo characteristics of alginate stability and
      biocompatibility.

PMID- 12182783
TI  - Endothelin-converting enzyme activity in human cerebral circulation.
AB  - OBJECTIVE: An increased level of endothelin (ET)-1 seems to be involved in the
      development of augmented cerebrovascular resistance in different pathological
      conditions, most notably vasospasm after subarachnoid hemorrhage. Therefore,
      interfering with the ET synthesis or ET receptor blockade may be a promising
      approach in the treatment of cerebral vasospasm after subarachnoid hemorrhage.
      Although the receptors mediating the effects of ET-1 human cerebrovasculature are
      well characterized, data concerning the functionally relevant ET-converting
      enzyme (ECE) activity are scarce. METHODS: ECE activity was determined in organ
      bath studies by the use of intraoperatively harvested human pial arteries. The
      level of ECE activity was analyzed by comparing the shift in the concentration
      effect curves obtained for ET-1 and its precursor, big ET-1. In addition, the
      presence of ECE-1alpha immunoreactivity was studied in human cerebral tissue.
      RESULTS: ECE-1alpha immunoreactivity was found, although not consistently, in
      human cerebral arteries and was restricted to the endothelium. In isolated pial
      arterial segments, ET-1 and big ET-1 induced concentration-related contractions
      with mean pD(2) values of 9.25 +/- 0.34 and 7.13 +/- 0.17, respectively, yielding
      a 123-fold shift of big ET-1 versus mature ET-1. Preincubation with
      phosphoramidon (10(-4) mol/L) resulted in a small yet significant inhibition of
      the contraction induced by big ET-1. CONCLUSION: The results of our study
      indicate the presence of functional ECE activity and ECE-1alpha immunoreactivity
      in human cerebral arteries. Furthermore, the data suggest the presence of ECE
      like activity that differs from that of ECE-1alpha.

PMID- 12182785
TI  - Sodium channel-blocking agents are not of benefit to rats with kaolin-induced
      hydrocephalus.
AB  - OBJECTIVE: Hydrocephalus causes damage to periventricular white matter at least
      in part through chronic ischemia. The sodium channel-blocking agents mexiletine
      and riluzole have been shown to be of some protective value in various models of
      neurological injury. We hypothesized that these agents would ameliorate the
      effects of experimental childhood-onset hydrocephalus. METHODS: Hydrocephalus was
      induced in 4-week-old rats by injection of kaolin into the cisterna magna. Tests
      of cognitive and motor function were performed on a weekly basis. In a blinded
      and randomized manner, mexiletine (0.7, 7, or 42 mg/kg/d) or riluzole (1.4 or
      13.6 mg/kg/d) was administered by osmotic minipump for 2 weeks, beginning 2 weeks
      after induction of hydrocephalus. The brains were then subjected to
      histopathological and biochemical analyses. RESULTS: Compared with untreated
      hydrocephalic rats, neither mexiletine nor riluzole was associated with a
      protective effect on behavioral, structural, or biochemical abnormalities.
      CONCLUSION: Protection of hydrocephalic brains through pharmacological sodium
      channel blockade is probably an approach not worth pursuing.

PMID- 12182786
TI  - Neurosurgery in the People's Republic of China: a century's review.
AB  - A CENTURY IS quite a short time in the history of humankind, but there have been
      significant happenings in the field of neurosurgery in China during the past
      century. We review the history of the founding and development of neurosurgery in
      China. We record these events faithfully, and we also dedicate this article to
      those pioneers, including Song-Tao Guan, Yi-Cheng Zhao, and others, who devoted
      their lives to neurosurgery in China.

PMID- 12182787
TI  - Radiosurgical treatment of a cerebral arteriovenous malformation in a patient
      with moyamoya disease: case report.
AB  - OBJECTIVE AND IMPORTANCE: A case of a cerebral arteriovenous malformation (AVM),
      which was treated with gamma knife surgery, in a patient with moyamoya disease is
      described. This is the first report of radiosurgical treatment of a cerebral AVM
      in a patient with moyamoya disease; the outcome was satisfactory. CLINICAL
      PRESENTATION: The patient presented with frequent episodes of transient ischemic
      attacks and seizures. INTERVENTION: Staged encephaloduroarteriosynangiosis was
      performed on both sides, with an interval of 10 months. Postoperative cerebral
      angiography demonstrated augmented cerebral perfusion, which increased the size
      of the AVM nidus. The patient subsequently underwent gamma knife surgery, and the
      AVM completely disappeared 2 years later. CONCLUSION: Radiosurgery may be a good
      treatment option for AVMs accompanying moyamoya disease, allowing the
      preservation of collateral vessels and the prevention of possible misery
      perfusion.

PMID- 12182788
TI  - Shaking limb transient ischemic attacks: unusual presentation of carotid artery
      occlusive disease: report of two cases.
AB  - OBJECTIVE AND IMPORTANCE: Shaking limb transient ischemic attacks (TIAs)
      represent a rare clinical syndrome that has been ascribed to focal cerebral
      ischemia attributable to insufficient brain perfusion, usually resulting from
      carotid artery occlusive disease. The techniques conventionally used to evaluate
      this condition are contrast angiography, carotid artery ultrasonography, and
      magnetic resonance angiography. Treatment consists of internal carotid artery
      (ICA) endarterectomy or, in the case of complete ICA occlusion, extracranial
      intracranial bypass. In this report, two patients with shaking limb TIAs are
      presented. For one patient, preoperative evaluations included single-photon
      emission computed tomographic studies with acetazolamide vasodilator challenge;
      for the second patient, computed tomographic angiography was used to assess
      vascular anatomic features. CLINICAL PRESENTATION: Two patients with severe
      carotid artery disease presented with brief, recurrent, shaking limb TIAs.
      Angiograms obtained for Patient 1 demonstrated complete ICA occlusion in
      association with severe external carotid artery stenosis, whereas preoperative
      single-photon emission computed tomographic scans revealed a lack of
      cerebrovascular reserve in response to acetazolamide challenge. Carotid artery
      duplex ultrasonography and computed tomographic angiography demonstrated severe
      stenosis of the ICA for Patient 2. INTERVENTION: Patient 1 underwent a left
      external carotid artery endarterectomy. Patient 2 underwent a right ICA
      endarterectomy. CONCLUSION: After surgery, the shaking limb episodes ceased for
      both patients. Postoperative single-photon emission computed tomographic scans
      for Patient 1 demonstrated increased cerebral blood flow in response to
      acetazolamide challenge. These data provide support for the concept that shaking
      limb TIAs are related to hemodynamic failure and that improvements in cerebral
      blood flow through conducting vessels can alleviate the condition.

PMID- 12182789
TI  - Primary meningeal osteosarcoma: case report and review of the literature.
AB  - OBJECTIVE AND IMPORTANCE: Primary meningeal osteosarcomas are extremely rare
      lesions; before this case report, only five cases had been reported in the
      literature. We encountered a patient with a meningeal osteosarcoma but no
      evidence of additional tumor at another remote site. CLINICAL PRESENTATION: A 56
      year-old man presented with progressive weakness of the right leg and the right
      arm. Computed tomography and magnetic resonance imaging revealed an extracerebral
      frontoparietal tumor on the left side. INTERVENTION: The patient underwent
      complete resection of the tumor and subsequent radiotherapy of the tumor region.
      The histological examination showed evidence of the osteosarcoma, which was
      confined to the meninges. Postoperative adjuvant radiotherapy was administered.
      There was no tumor recurrence during 3 years of postoperative follow-up. Because
      the patient had no risk factors or further osteosarcomas, primary meningeal
      development was assumed. CONCLUSION: Despite their rarity, osteosarcomas must be
      considered in the differential diagnosis of meningeal tumors.

PMID- 12182790
TI  - Lateral supratentorial endodermal cyst: case report and review of literature.
AB  - OBJECTIVE AND IMPORTANCE: Epithelial cysts of the central nervous system are
      unusual entities, with the majority reported to occur in the spinal canal. More
      unusual is the intracranial presentation, which shows a predilection for midline
      localization in the posterior fossa, brainstem, and suprasellar regions. This
      report discusses the differential diagnosis, pathogenesis, radiographic
      presentation, and therapeutic considerations of a laterally positioned cerebral
      convexity endodermal cyst. CLINICAL PRESENTATION: A 49-year-old right-handed man
      presented with approximately a 30-month history of short- and long-term memory
      difficulties. A magnetic resonance imaging study revealed a large, nonenhancing,
      extra-axial cystic lesion overlying the right lateral frontal convexity.
      INTERVENTION: A right frontoparietal craniotomy exposed a large extra-axial cyst
      with an opaque, yellowish-white membrane containing a mucoid fluid. Histological
      analysis disclosed a layer of unremarkable, ciliated columnar epithelium with a
      basement membrane that stained positive for cytokeratin, periodic acid-Schiff,
      and Alcian blue. No evidence of either a muscular or cartilaginous layer around
      the mucosa was present to further delineate neurenteric versus bronchogenic
      origin of the cyst. CONCLUSION: This case involved the occurrence of a solitary
      endodermal cyst as an extra-axial mass localized over the lateral frontal lobe.
      The lateral supratentorial localization of this lesion illustrates the need for
      consideration of the pathogenesis of this entity as well as its diagnostic
      differentiation from other cystic abnormalities in this region. A review of the
      histochemistry of endodermal, neuroepithelial, and other cerebral cysts is
      presented.

PMID- 12182792
TI  - Far lateral extraforaminal lumbar synovial cyst: report of two cases.
AB  - OBJECTIVE AND IMPORTANCE: We present two cases of a far lateral extraforaminal
      synovial cyst at the L5-S1 level of the spine. Neither case was diagnosed as a
      synovial cyst before surgery because of their atypical location. Only one other
      case of an extraforaminal synovial cyst, located at L4-L5, has been reported in
      the literature. CLINICAL PRESENTATION: Both women presented with radicular leg
      pain and examination findings consistent with L5 root compression. INTERVENTION:
      During surgery, the cyst was not associated with the facet joint. One cyst was
      adherent to the nerve root. Both cysts were completely resected, with excellent
      pain relief. CONCLUSION: These cases serve as a stimulus to look outside the
      spinal canal and foramen in patients with symptoms suggesting nerve root
      compression. Far lateral extraforaminal synovial cyst should be included in the
      differential diagnosis.

PMID- 12182791
TI  - Endoscopic third ventriculostomy for treatment of noncommunicating syringomyelia
      associated with a Chiari I malformation and hydrocephalus: case report and
      pathophysiological considerations.
AB  - OBJECTIVE AND IMPORTANCE: A Chiari I malformation associated with syringomyelia
      and hydrocephalus is a rare condition. We report the successful use of endoscopic
      third ventriculostomy for the treatment of this pathological entity. The
      successful use of this technique in such a case has not been previously
      described, and the results allow us to speculate on the pathophysiological
      mechanism involved. CLINICAL PRESENTATION: A 34-year-old woman presented with
      headaches, a motor deficit of the right upper limb, and gait dyspraxia. Magnetic
      resonance imaging scans demonstrated dilation of all ventricles, compression of
      the retrocerebellar cerebrospinal fluid space, downward displacement of the
      tonsils, and syringomyelia. Syringomyelia involved the cervicodorsal cord below
      C3, with a syrinx-free segment between C1 and C3 and no enlargement of the
      rostral part of the central canal. INTERVENTION: Endoscopic third ventriculostomy
      resulted in prompt improvement of the clinical symptoms. Postoperative magnetic
      resonance imaging scans demonstrated shrinkage of the syrinx and return of the
      cerebellar tonsils to their physiological positions. CONCLUSION: This experience
      demonstrates that endoscopic third ventriculostomy, which is a simple, safe
      technique, may be the treatment of choice for associated Chiari I malformations,
      hydrocephalus, and syringomyelia (even the noncommunicating type).

PMID- 12182793
TI  - Spinal epidural abscess successfully treated with percutaneous, computed
      tomography-guided, needle aspiration and parenteral antibiotic therapy: case
      report and review of the literature.
AB  - OBJECTIVE AND IMPORTANCE: We describe a case of a posterior spinal epidural
      abscess that was successfully treated with percutaneous, computed tomography
      guided, needle aspiration and parenteral antibiotic therapy. CLINICAL
      PRESENTATION: A 48-year-old man experienced acute pain in the paralumbar region
      for 1 week, followed by gait disturbance and micturition difficulty. Laboratory
      studies demonstrated leukocytosis and hyperglycemia. Blood cultures yielded
      Staphylococcus aureus. Magnetic resonance imaging scans of the thoracolumbar
      spine revealed a posterior spinal epidural abscess located between L2 and the
      lower cervical spine. INTERVENTION: The patient's low back pain persisted despite
      10 days of antibiotic therapy. Therefore, percutaneous, computed tomography
      guided, needle aspiration was performed. The low back pain was relieved
      dramatically and immediately after the procedure. The spinal epidural abscess
      completely resolved after 6 weeks of antibiotic treatment. CONCLUSION: Surgical
      decompression and antibiotic therapy are the treatments of choice for patients
      with spinal epidural abscesses. Selected patients may be treated nonsurgically.
      Rarely, percutaneous drainage of the abscess has been reported to be helpful. Our
      case suggests that percutaneous, computed tomography-guided, needle aspiration
      might be a rational alternative to surgical decompression for treatment of spinal
      epidural abscesses.

PMID- 12182794
TI  - Use of FloSeal hemostatic sealant in transsphenoidal pituitary surgery: technical
      note.
AB  - OBJECTIVE: Bleeding during transsphenoidal pituitary surgery can lead to a
      variety of operative difficulties. When the endonasal transsphenoidal approach is
      used, even mild intraoperative hemorrhage can lessen visibility in the confined
      operative field of view. This technical note describes the use of a hemostatic
      agent we have found of benefit in obtaining prompt hemostasis during this
      operation. METHODS: Operative records were reviewed for an 18-month period for
      all patients who underwent transsphenoidal surgery since we began using FloSeal
      hemostatic sealant in January 2000. RESULTS: During the study period, 293
      transsphenoidal operations were performed for pituitary lesions. Of these, 20
      procedures involved vigorous or persistent bleeding. When the standard techniques
      for hemostasis failed or were inadequate, FloSeal, a sterile mixture of a gelatin
      matrix and thrombin component mixed at the time of use, was applied to the site
      of hemorrhage by use of a 14-gauge angiocatheter to reach the sella. We observed
      complete hemostasis immediately on application of FloSeal in all cases except
      one, which required a second application. Hemostasis was obtained immediately
      after the second application. No operations were aborted during this period as a
      consequence of undue bleeding. CONCLUSION: We detail the method in which we use
      FloSeal in transsphenoidal surgery and report our impression of its
      effectiveness. FloSeal has been demonstrated to be safe and biocompatible as
      compared with hemostatic agents currently in use.

PMID- 12182796
TI  - How tutors assist adults with learning disabilities to use virtual environments.
AB  - PURPOSE: To describe strategies used by tutors teaching adults with learning
      disabilities to use desktop virtual environments and to investigate their
      effectiveness by examining changes over time in tutor and learner behaviour.
      METHOD: Twenty adults with learning disabilities spent 12 sessions with one of
      four non-disabled tutors learning to use desktop virtual environments designed to
      teach independent living skills. Sessions were recorded on videotape, categories
      of behaviour were described and tapes analysed for frequency of tutor behaviours
      and goals achieved by learners. RESULTS: Tutor strategies were described in terms
      of whether they aimed to help the learner master the interaction devices or to
      navigate and achieve goals in the virtual environments and how directive they
      were. There were some differences between tutors but this did not relate to
      whether tutors were experienced users themselves of the environments or were
      initially unfamiliar with them. Goal achievement was maintained at a constant
      level while help with the interaction devices and specific information about the
      environment decreased over repeated sessions. Rates of non-specific information
      did not change. CONCLUSIONS: Pretraining with the interaction devices would free
      both tutor and learner to concentrate on achieving goals in the environments.
      Much of the specific help given by the tutor could be incorporated into the
      software.

PMID- 12182797
TI  - Control of virtual environments for young people with learning difficulties.
AB  - PURPOSE: The objective of this research is to identify the requirements for the
      selection or development of usable virtual environment (VE) interface devices for
      young people with learning disabilities. METHOD: A user-centred design
      methodology was employed, to produce a design specification for usable VE
      interface devices. Details of the users' cognitive, physical and perceptual
      abilities were obtained through observation and normative assessment tests.
      CONCLUSIONS: A review of computer interface technology, including virtual reality
      and assistive devices, was conducted. As there were no devices identified that
      met all the requirements of the design specification, it was concluded that there
      is a need for the design and development of new concepts. Future research will
      involve concept and prototype development and user-based evaluation of the
      prototypes.

PMID- 12182798
TI  - Design guidelines for interactive multimedia learning environments to promote
      social inclusion.
AB  - PURPOSE: There is a continuing need for guidelines to aid in the design of
      Interactive Multimedia Learning Environments (IMLE) to promote effective
      learning. The project introduced in this paper looks at an important subset of
      this problem, the design of interactive learning environments to promote social
      inclusion. METHOD: A consortium of six partners contributed toward defining
      learning material to develop a range of work based skills, including
      horticulture, IT and catering. These were then developed into IMLE prototypes.
      Formative evaluation of these prototypes then revealed a range of usability
      problems, which were grouped into generic types and frequency of occurrence.
      RESULTS: The most important and frequently occurring problems were used to distil
      a set of design guidelines for the development of effective IMLE. The results
      from this usability content analysis were also used to refine the initial
      prototypes to improve their usability and effectiveness. CONCLUSIONS: These
      guidelines, termed the Greenhat Design Guidelines, can be adopted for use by all
      multimedia developers aiming to promote the social inclusion of vulnerable or
      socially disadvantaged groups of people. The refined IMLE can be accessed via the
      Greenhat Server to improve the employment-related skills of socially excluded
      people.

PMID- 12182799
TI  - The role of virtual reality technology in the assessment and training of
      inexperienced powered wheelchair users.
AB  - PURPOSE: The current paper provides quantitative and qualitative data concerning
      the application of two virtual environments to the assessment and training of
      inexperienced powered wheelchair users, both in terms of the ability to control
      the chair accurately without hitting objects in the environment (manoeuvrability)
      and in terms of being able to find ones way around a complex environment without
      becoming lost (route-finding). METHOD: Six novice powered wheelchair users
      participated in the project, completing either the manoeuvrability or route
      finding components of the study. Performance measures were taken in real life pre
      and post training and throughout virtual reality sessions. Participants also
      completed a questionnaire regarding the aesthetics of the virtual environments
      and aspects of the powered wheelchair simulation. RESULTS: The participants rated
      the aesthetics of the virtual environments positively and engaged well with the
      virtual system. However, they found the manoeuvrability tasks considerably more
      difficult in virtual reality (VR) than in real life. Some difficulties with
      controlling the simulated wheelchair were apparent. Some improvements on virtual
      and real life manoeuvrability tasks and route finding were noted following
      conventional and virtual training. CONCLUSIONS: The study indicated that the two
      virtual environments represent a potentially useful means of assessing and
      training novice powered wheelchair users. The virtual environments however must
      become less challenging if they are to represent a motivating and effective means
      of improving performance. Further development of the way in which wheelchair
      movement is controlled and simulated represents a key element in this multi stage
      project.

PMID- 12182800
TI  - Talk your way round--a speech interface to a virtual museum.
AB  - PURPOSE: To explore the development of a speech interface to a virtual world and
      to consider its relevance for disabled users. METHOD: The system was developed
      using mainly software that is available at minimal cost. How well the system
      functioned was assessed by measuring the number of times a group of users with a
      range of voices had to repeat commands in order for them to be successfully
      recognized. During an initial session, these users were asked to use the system
      with no instruction to see how easy this was. RESULTS: Most of the spoken
      commands had to be repeated less than twice on average for successful
      recognition. For a set of 'teleportation' commands this figure was higher (2.4),
      but it was clear why this was so and could easily be rectified. The system was
      easy to use without instruction. Comments on the system were generally positive.
      CONCLUSIONS: While the system has some limitations, a virtual world with a
      reasonably reliable speech interface has been developed almost entirely from
      software which is available at minimal cost. Improvements and further testing are
      considered. Such a system would clearly improve access to virtual reality (VR)
      technologies for those without the skills or physical ability to use a standard
      keyboard and mouse. It is an example of both assistive technology (AT) and
      universal design.

PMID- 12182801
TI  - Visualization tools for blind people using multiple modalities.
AB  - PURPOSE: There are many problems when blind people need to access visualizations
      such as graphs and tables. Current speech or raised-paper technology does not
      provide a good solution. Our approach is to use non-speech sounds and haptics to
      allow a richer and more flexible form of access to graphs and tables. METHOD: Two
      experiments are reported that test out designs for both sound and haptic graph
      solutions. In the audio case a standard speech interface is compared to one with
      non-speech sounds added. The haptic experiment compares two different graph
      designs to see which was the most effective. RESULTS: Our results for the sound
      graphs showed a significant decrease in subjective workload, reduced time taken
      to complete tasks and reduced errors as compared to a standard speech interface.
      For the haptic graphs reductions in workload and some of the problems that can
      occur when using such graphs are shown. CONCLUSIONS: Using non-speech sound and
      haptics can significantly improve interaction with visualizations such as graphs.
      This multimodal approach makes the most of the senses our users have to provide
      access to information in more flexible ways.

PMID- 12182802
TI  - An evaluation of the efficacy of training people with learning disabilities in a
      virtual environment.
AB  - PURPOSE: To evaluate the efficacy of using a virtual kitchen for vocational
      training of people with learning disabilities. METHOD: Twenty four catering
      students with learning disabilities participated in the study. Half the students
      were currently being trained in the kitchen on which the virtual kitchen was
      modelled but the remaining students were unfamiliar with this kitchen. Students
      were first pre-tested on four food preparation tasks and identification of 12
      hazards in their own training kitchens. They were subsequently trained on one
      food preparation task and three hazards in their own training kitchens, one food
      preparation task and three hazards in the virtual kitchen, and one food
      preparation task and three hazards in specially designed workbooks. They were
      then retested in their own training kitchens on all the food preparation tasks
      and all the hazards. RESULTS: Virtual training was found to be as beneficial as
      real training and more beneficial than workbook and no training in the food
      preparation tasks. However, virtual, real and workbook training were found to be
      equally beneficial in the hazard identification task. Students who were
      unfamiliar with the kitchen on which the virtual kitchen was modelled benefited
      from virtual training to the same extent as students who were familiar with the
      kitchen. CONCLUSIONS: Vocational students with learning disabilities were able to
      use the virtual environment and were motivated to learn using this training
      method. Depending on the task being trained, virtual training had a more
      beneficial effect on real task performance than workbook training, even when the
      virtual kitchen was not modelled on the real training kitchen.

PMID- 12182803
TI  - An exploratory investigation into the usability and usefulness of training people
      with learning disabilities in a virtual environment.
AB  - PURPOSE: Two studies sought to answer the following questions. Are people with
      learning disabilities capable of using a virtual environment? Are they motivated
      to learn using this training method? Do they show any benefit from using a
      virtual environment? Does any benefit transfer to improved real world
      performance? METHOD: In the first study, 30 students with learning disabilities
      were sequentially allocated to an active or a passive experimental group. Active
      participants explored a virtual bungalow searching for a toy car. Passive
      participants watched the exploration undertaken by the preceding active
      participant and searched for the toy car. All participants then performed spatial
      and object recognition tests of their knowledge of the virtual environment. In
      the second study, the errors of 45 participants on a real steadiness tester task
      were noted before they were randomly allocated to three groups-a real training
      group, a virtual training group and a no training group. After training, the
      participants performed a second test trial on the real steadiness tester.
      RESULTS: The students were capable of using a virtual environment and were
      motivated to use this training method. Active exploration of a virtual
      environment was found to enhance their memory of the spatial layout of the
      bungalow but not their memory of the virtual objects. In the second study,
      virtual training was found to transfer to real task performance. CONCLUSIONS:
      These two laboratory-based studies provide answers to four important questions
      concerning virtual training of people with learning disabilities. Hopefully, the
      findings will encourage this training aid to be used more widely.

PMID- 12182805
TI  - Guest editorial.

PMID- 12182804
TI  - The virtual courtroom: a view of justice. Project to prepare witnesses or victims
      with learning disabilities to give evidence.
AB  - PURPOSE: With the advent of 'The Youth Justice and Criminal Evidence Act 1999'
      passed by Parliament in August 1999, vulnerable witnesses can for the first time
      give evidence to the court with the support of 'special measures'. People with a
      learning disability fall into the category of vulnerable witnesses, and the
      purpose of this paper is to describe the development of the virtual courtroom, a
      virtual reality (VR) and multimedia based training platform to prepare this group
      of people for such an eventuality. METHOD: A user-centred design methodology was
      adopted, with a user group being formed of students and adults with learning
      disabilities. This group, working together with facilitators, experts on the new
      act, and experienced designers of VR based training systems, designed and
      implemented the virtual courtroom. RESULTS: The virtual courtroom model has been
      produced using the Realimation Virtual Reality software tool. The next stage of
      the project is to design and develop three multimedia-based scenarios showing a
      variety of situations in which a person with a learning disability could give
      evidence in court. CONCLUSION: One of the recommendations in the 'Speaking up for
      justice' report, suggested that the Home Office develop further material to
      assist vulnerable witnesses to prepare for their attendance at court. The virtual
      courtroom provides one of the first and most innovative of such solutions.

PMID- 12182806
TI  - A comparative ultrastructural study of spermatozoa of the teiid lizards
      Cnemidophorus gularis gularis, Cnemidophorus ocellifer, and Kentropyx
      altamazonica (Reptilia, Squamata, Teiidae).
AB  - The ultrastructure of the spermatozoa of Cnemidophorus gularis gularis,
      Cnemidophorus ocellifer, and Kentropyx altamazonica is described for the first
      time. Mature spermatozoa of Cnemidophorus spp. and K. altamazonica differ in the
      occurrence of a perforatorial base plate, the enlargement of axonemal fibers 3
      and 8, and shape of mitochondria. The comparisons of the ultrastructure sperm of
      Cnemidophorus spp. and K. altamazonica with Ameiva ameiva [J. Morphol. (2002) in
      press] suggest that Ameiva and Cnemidophorus are more similar to each other than
      either is to Kentropyx. Statistical analyses reveal that sperm of all three
      species studied are significantly different in the following dimensions: head,
      acrosome, distal centriole length, and nuclear shoulders width. There was no
      variable statistically different between the Cnemidophorus spp. only. The length
      of the tail, midpiece, entire sperm, and nuclear rostrum are significantly
      different between K. altamazonica and Cnemidophorus spp. Our results indicate
      that sperm ultrastructure presents intra and intergeneric variability.

PMID- 12182807
TI  - Postnatal mammary ductal growth: three-dimensional imaging of cell proliferation,
      effects of estrogen treatment, and expression of steroid receptors in prepubertal
      calves.
AB  - Cows may provide insights into mammary development that are not easily obtained
      using mouse models. Mammary growth in control and estrogen-treated calves was
      investigated to evaluate general patterns of proliferation and relationship to
      estrogen receptor (ER) expression. After in vivo labeling with bromodeoxyuridine
      (BrdU), serial histological sections of mammary tissue were used to generate
      three-dimensional reconstructions. BrdU-labeled cells were present throughout the
      highly branched terminal ducts. ER and progesterone receptors (PR) were
      colocalized in nuclei of ductal epithelial cells. However, basal cells and
      epithelial cells that were located in the central region of epithelial cords and
      those that lined the lumen of patent ducts were ER- and PR-negative, as were
      stromal cells. Cells along the basal portion of the epithelium were not
      myoepithelial. ER in mammary epithelial cells but not stromal cells is analogous
      to patterns in human breast but contrasts with localization in murine mammary
      gland. After estrogen stimulation, 99% of BrdU-labeled (and Ki67-labeled)
      epithelial cells were ER-negative. Data suggest that proliferation in response to
      estrogen treatment was initiated within ER-positive epithelial cells of the
      developing mammary gland and the signal was propagated in paracrine fashion to
      stromal elements and ER-negative epithelial cells.

PMID- 12182808
TI  - Cell proliferation in bovine mammary epithelium: identification of the primary
      proliferative cell population.
AB  - Histologic analyses indicate that a lightly staining cell population present in
      mammary parenchyma may function as mammary stem cells. We performed an analysis
      of mammary epithelial cell proliferation in prepubertal bromodeoxyuridine (BrdU)
      injected Holstein heifers to investigate this hypothesis. We observed light,
      dark, and intermediate staining cells in histologic sections stained with basic
      fuschin and azure II. Light cells comprised 10% of the total parenchymal cell
      population but accounted for 50% of the cell proliferation. Intermediate cells
      comprised 60% of the cell population and 43% of proliferating cells. Dark cells
      comprised 30% of the parenchymal cell population but only 7% of proliferating
      cells. The distribution of BrdU+ cells across basal, embedded, and lumenal
      parenchymal cell layers was correlated with the fraction of total parenchymal
      cells present in each layer (r=0.99). However, the proportion of mitotic cells
      observed in the basal cell layer was only half of what would be predicted by the
      BrdU-labeling data. This observation suggests that some basal cells either arrest
      in G(2) or migrate into the suprabasal epithelial layers before undergoing
      mitosis. These results strongly support the concept that lightly staining mammary
      parenchymal cells are the primary proliferative cell population.

PMID- 12182809
TI  - Different regulatory elements within the MyoD promoter control its expression in
      the brain and inhibit its functional consequences in neurogenesis.
AB  - MyoD is a key basic helix-loop-helix (bHLH) transcription factor capable of
      converting many cells into skeletal muscle. Together with Myf5 it is essential
      for initiating skeletal myogenesis. In this report, the restricted domains of
      MyoD-lacZ expression have been revealed in the embryonic mouse brain by the
      analysis of transgenic mice with reporter genes driven by MyoD regulatory
      elements. The MD6.0-lacZ transgene was localized in the basal plate of pons,
      medulla oblongata (i.e. the medial longitudinal fasciculus) and spinal cord of
      wild-type and mutant mouse embryos at various stages of development, whereas the
      258/-2.5lacZ transgene was not detected in the brain. In addition, MyoD RNA and
      MyoD protein accumulations were monitored in neurons expressing MD6.0-lacZ
      transgene. Although MyoD was detected in muscle myotomal cells, it was absent in
      MD6.0-lacZ-expressing neurons. This would account for the lack of myogenic
      conversion in brain structures and the absence of a neural phenotype in MyoD-/-
      embryos and mice. Together, these data indicate that within the promoter of MyoD
      different regulatory elements control its expression and prevent the functional
      consequences of MyoD in neurogenesis.

PMID- 12182810
TI  - Different expressions of connexin 43 and 32 in the fibroblasts of human dental
      pulp.
AB  - The expression and localization of gap junctional proteins connexin (Cx) 26, 32,
      and 43 was examined in human dental pulp. Dental pulp tissues were obtained from
      human third molars immediately after extraction. Some pulp tissues were used for
      cell culture, and the rest for histological observations. Immunostaining for
      cultured dental pulp fibroblasts (DPFs) showed that Cx32 and 43 were expressed in
      human DPFs, and proteins corresponding to 27 (Cx32) and 43kDa (Cx43) were
      identified by Western blot analysis. Immunostaining for tissue sections showed
      that the expression of Cx32 and 43 was observed in the entire region of the pulp
      and further strong expression of Cx32 was established beneath the cell-rich zone.
      Considering the close relationship between Cx types and cell functions, the
      results indicate that DPFs beneath the cell-rich zone may have specific, Cx32
      related functions. The cell rich zone is thought to contain progenitor
      odontoblasts that can be induced to differentiate into mature odontoblasts in
      response to wounding. Therefore, it may be hypothesized that DPFs just beneath
      the cell-rich zone produce proteins and induce odontoblast differentiation from
      the cells in the cell-rich zone.

PMID- 12182811
TI  - Stereology and ultrastructure of the seminal vesicle of C57/BL/6J mice following
      chronic alcohol ingestion.
AB  - Excessive alcohol consumption causes metabolic changes and pathologic alterations
      in testes and accessory sex organ in different animal species. The aim of the
      present study was to evaluate the macroscopic, histologic and ultrastructural
      alterations provoked by chronic ingestion of different ethanol concentrations
      over increasing periods of time on the secretory epithelium of the seminal
      vesicle of C57/BL/6J mice in using stereological methods. Sixty male adult mice
      were divided into three experimental groups: Control, Alcoholic 25% and Alcoholic
      35%, respectively, receiving tap water and tap water containing ethanol diluted
      to 25 and 35 degrees Gay Lussac. All mice were fed with the same solid diet.
      After 150 and 250 days of treatment the animals were sacrificed and the seminal
      vesicles were collected and processed for light and transmission electron
      microscopy. The cellular, cytoplasmic and nuclear volumes and the area density of
      autophagic and secretory vacuoles were measured. The histologic alterations
      observed in the alcoholic mice consisted of a reduction in epithelial size and
      cell volume, with maintenance of the same nuclear and cytoplasmic ratio as
      verified in the control groups. The ultrastructural alterations were: increased
      density of dense body area, decreased density of secretory granule area, and
      dilated rough endoplasmic reticulum and Golgi cisternae. We conclude that chronic
      ethanol ingestion causes depleting morphologic alterations in the epithelial
      cells of the seminal vesicle and negatively affects the secretory process of this
      gland.

PMID- 12182812
TI  - Low temperature FESEM of the calcifying interface of a scleractinian coral.
AB  - The ultrastructural nature of the calcifying interface in the scleractinian coral
      Galaxea fascicularis has been investigated using high-resolution, low temperature
      field emission scanning electron microscopy (FESEM). This technique permitted
      structural analyses of soft tissue and skeleton in G. fascicularis in a frozen
      hydrated state, without the need for chemical fixation or decalcification.
      Structural comparisons are made between frozen-hydrated polyps and polyps that
      have undergone conventional fixation and decalcification. Vesicles expelled by
      the calicoblastic ectodermal cells into sub-skeletal spaces and previously
      suggested to play a role in calcification were commonly observed in fixed samples
      but were distinctly absent in frozen-hydrated preparations. We propose that these
      vesicles are fixation artefacts. Two distinct types of vesicles (380 and 70 nm in
      diameter, respectively), were predominant throughout the calicoblastic ectodermal
      cells of frozen-hydrated preparations, but these were never seen to be entering,
      or to be contained within, sub-skeletal spaces, nor did they contain any
      crystalline material. In frozen-hydrated preparations, membranous sheets were
      seen to surround and isolate portions of aboral mesogloea and to form junctional
      complexes with calicoblastic cells. The calicoblastic ectoderm was closely
      associated with the underlying skeleton, with sub-skeletal spaces significantly
      smaller (P<0.0001) in frozen-hydrated polyps compared to fixed polyps. A network
      of organic filaments (26 nm in diameter) extended from the apical membranes of
      calicoblastic cells into these small sub-skeletal cavities. A thin sheath was
      also frequently observed adjacent to the apical membrane of calicoblastic cells.

PMID- 12182813
TI  - Kalisomes in corals: a novel KCl concentrating organelle?
AB  - Large membrane-bound inclusions were clearly visible within the gastrodermis and
      lipid-containing cells of planulae and settled larvae of the zooxanthellate
      coral, Pocillopora damicornis after fixation or freeze-substitution. We suggest
      that these inclusions may be a novel potassium (kalium) chloride concentrating
      organelle, for which we propose the name kalisome. The inclusions were more
      abundant in settled larvae than in planulae and were not present in mature
      polyps. In planulae of the azooxanthellate coral, Dendrophyllia sp. these
      inclusions were extremely rare. Quantitative X-ray microanalysis of freeze
      substituted preparations showed that the inclusions in P. damicornis settled
      larvae contained very high, positively correlated, concentrations of K (2.5 mol x
      kg(-1)) and Cl (2.5 mol x kg(-1)). Lower concentrations of both K (1.2 mol x kg(
      1)) and Cl (1.3 mol x kg(-1)) were detected in P. damicornis planulae, yet higher
      concentrations were measured in Dendrophyllia planulae (K=6.0 mol x kg(-1);
      Cl=5.1 mol x kg(-1)). No significant (P>0.05) differences in concentration were
      observed between inclusions in freeze-substituted and freeze-dried sections of
      planulae. Symbiotic algae (zooxanthellae) in P. damicornis planulae and settled
      larvae also contained deposits with high levels of K and Cl, but these were not
      positively correlated and no structures associated with them were retained by
      fixation. Significant (P<0.05) concentration differences were also observed
      between deposits in freeze-substituted and freeze-dried sections. However,
      similar to 'kalisomes,' zooxanthellae deposits were more abundant in settled
      larvae than planulae and absent in mature polyps. Higher concentrations of K and
      Cl were also detected in settled larvae (K=0.7 mol x kg(-1); Cl=1.1 mol x kg(-1))
      in comparison to planulae (K=0.4 mol x kg(-1); Cl=0.5 mol x kg(-1)).

PMID- 12182814
TI  - Functional morphology of adult female Culex quinquefasciatus midgut during blood
      digestion.
AB  - The adult female Culex quinquefasciatus midgut comprises a narrow anterior and a
      dilated posterior region, with epithelia composed of a monolayer of adjacent
      epithelial cells joined at the apical portion by septate junctions. Densely
      packed apical microvilli and an intricate basal labyrinth characterise each cell
      pole. Our morphological studies suggest that, during blood digestion, the
      anterior midgut region also participates in an initial absorptive stage which is
      probably related to the intake of water, salts and other small molecules. This
      activity peaked by 6h after bloodmeal feeding (ABF) and ended approximately 18 h
      ABF, when the peritrophic membrane was already formed. After this time,
      absorption only occurred in the posterior region, with morphologic and
      biochemical evidence of high synthetic activity related to the secretion of
      proteases. Chymotrypsin, elastase, aminopeptidase, and trypsin reached their
      maximum activity at around 36 h ABF. Digestion products were apparently absorbed
      and transported to the basal labyrinth, from where they should be released to the
      hemolymph. At 72 h ABF, proteolysis had already ended and protein levels had
      returned to those observed before blood meal. The epithelium of the posterior
      region, however, did not return to its initial morphology, appearing quite
      disorganised. Additionally, from 48 h ABF onwards some epithelial cells showed
      morphological signals of apoptosis.

PMID- 12182815
TI  - Expression and purification of recombinant full-length NS3 protease-helicase from
      a new variant of Hepatitis C virus.
AB  - Viral mRNA extracted from the serum of a patient infected with HCV strain 1a was
      used for cloning, expression, and purification of full-length Hepatitis C NS3
      protein. Sequencing of the protease gene identified the virus to be a new variant
      closely related to strain H77, differing in 15 out of 631 amino acids in the NS3
      protein, none of which were predicted to be directly involved in catalysis,
      binding of substrate, or cofactor. A pBAD expression system was used to express
      the enzyme with an N-terminal tag in Escherichia coli. Purification from the
      soluble cellular fraction was achieved by Ni(2+)-IMAC and PolyU Sepharose
      affinity chromatography. The dependence of the proteolytic activity of the full
      length NS3 protein on ionic strength, glycerol concentration, and a peptide
      corresponding to the activating region of NS4A was analyzed and used to design an
      activity assay that is suitable for inhibition studies. The kinetic constants
      (k(cat) and K(M)) for catalysis and the inhibitory potencies (IC(50) and K(i)) of
      five product-based hexapeptide inhibitors were comparable to those reported for
      the truncated NS3 protein. Detailed kinetic and inhibition studies using this
      variant of full-length NS3 can increase the understanding of the enzymatic
      characteristics of NS3, reveal the importance of the substituted amino acids and
      the significance of the genetic variability for design of effective inhibitors of
      the virus, and is thus of relevance for drug discovery.

PMID- 12182816
TI  - A micro-scale process for high-throughput expression of cDNAs in the yeast
      Saccharomyces cerevisiae.
AB  - Methods have been developed aimed at applying at high-throughput technology for
      expression of cloned cDNAs in yeast. Yeast is a eukaryotic host, which produces
      soluble recombinant proteins and is capable of introducing post-translational
      modifications of protein. It is, thus, an appropriate expression system both for
      the routine expression of various cDNAs or protein domains and for the expression
      of proteins, which are not correctly expressed in Escherichia coli. Here, we
      describe a standard system in Saccharomyces cerevisiae, based on a vector for
      intracellular protein expression, where the gene products are fused to specific
      peptide sequences (tags). These epitope tags, the N-terminal His(6) tag and the C
      terminal StrepII tag, allow subsequent immunological identification and
      purification of the gene products by a two-step affinity chromatography. This
      method of dual-tagged recombinant protein purification eliminates contamination
      by degraded protein products. A miniaturization of the procedures for cloning,
      expression, and detection was performed to allow all steps to be carried out in
      96-well microtiter plates. The system is, thus, suitable for automation. We were
      able to analyze the simultaneous protein expression of a large number of cDNA
      clones due to the highly parallel approach of protein production and
      purification. The microtiter plate technology format was extended to quantitative
      analysis. An ELISA-based assay was developed that detects StrepII-tagged
      proteins. The application of this high-throughput expression system for protein
      production will be a useful tool for functional and structural analyses of novel
      genes, identified by the Human Genome Project and other large-scale sequencing
      projects.

PMID- 12182817
TI  - cDNA cloning, high-level expression, purification, and characterization of an
      avian Cu,Zn superoxide dismutase from Peking duck.
AB  - As a special species of avian, Peking duck is often used as a model for exploring
      effective factors against cardio-cerebrovascular diseases, and therefore
      investigations of antioxidant enzymes including superoxide dismutase are
      intriguing. By using 3(')-RACE with a gene-specific primer, a cDNA encoding duck
      Cu,Zn SOD was amplified from the total RNA extracted from Peking duck liver.
      Three free cysteine residues are found in the deduced amino acid sequence of duck
      SOD, among which Cys153 at the carbonyl-terminal is a distinctive feature.
      Production with a high yield of recombinant duck Cu,Zn SOD was achieved in
      Escherichia coli after the reconstituted expression vector pET-3a-dSOD was
      transformed into the bacterial strain BL21(DE3)pLysS. After two steps of anion
      exchange chromatography, a great quantity of the purified enzyme (100mg/L
      fermented culture) with an enzymatic activity comparable to that of native duck
      and bovine SOD was finally obtained. Duck SOD is a homodimer with 153 residues
      for each subunit. The molecular mass of the recombinant enzyme is 15,540.0Da
      measured by mass spectrum, which well coincides with the estimated size of the
      sequence but significantly differs from that of the native counterpart. Five
      charge isomers were observed on isoelectricfocusing (IEF). The most interesting
      observation is that the thermal stability of duck SOD is much lower than that of
      the bovine enzyme as revealed by irreversible heat inactivation at 70 degrees C.
      These properties are discussed in relation to the distinctive free Cys residues
      in duck Cu,Zn SOD.

PMID- 12182818
TI  - Extraction and purification of decorin from corneal stroma retain structure and
      biological activity.
AB  - We developed a method to purify decorin core protein from tissue with the goal of
      preserving its native structure and biological function. Currently, most
      procedures rely on the use of denaturing reagents potentially altering the
      biological activity. Decorin was purified from corneal stromas without the use of
      detergents or chaotropic reagents. Proteoglycans isolated using anion exchange
      chromatography on Q-Sepharose were treated with chondroitinase ABC. Decorin was
      isolated by a second Q-Sepharose chromatography with affinity chromatographies on
      heparin-Sepharose and concanavalin A-Sepharose. SDS-PAGE revealed a 98.4% pure
      44kDa protein identified as decorin with a yield of 35mg per 100 bovine corneas.
      Identification was confirmed by NanoESI and MALDI qTOF. The novel inclusion of
      20% propylene glycol in extraction and column buffers resulted in recoveries of
      proteoglycans comparable with those observed with detergents and urea. Purified
      decorin did alter the rate of fibrillogenesis of type I collagen and inhibited
      the lateral fusion of collagen fibrils. It also bound to [125I]TGF-beta1 with an
      apparent K(d) of 40nM. Circular dichroism spectroscopy of decorin displayed the
      spectra of alpha-helices and beta-pleated sheets consistent with those obtained
      from recombinant decorin. Urea-induced unfolding was cooperative and reversible
      while thermal denaturation caused irreversible unfolding. Native decorin can be
      purified from tissue in quantity and quality for biophysical, biochemical, and
      biological assays.

PMID- 12182819
TI  - High level expression and secretion of truncated forms of herpes simplex virus
      type 1 and type 2 glycoprotein D by the methylotrophic yeast Pichia pastoris.
AB  - Herpes simplex virus type 1 and 2 (HSV-1 and -2) glycoproteins D (gD-1 and gD-2)
      play a role in the entry of the virus into the host cell. Availability of
      substantial amounts of these proteins, or large fragments thereof, will be needed
      to allow studies at the molecular level. We studied the potency of the Pichia
      pastoris yeast expression system to produce soluble forms of gD. The DNA
      sequences encoding the extracellular domains of gD [amino acids 1-314 (gD-1(1
      314)) and amino acids 1-254 (gD-1(1-254)) of gD-1 and amino acids 1-314 of gD-2
      (gD-2(1-314))] were cloned into the P. pastoris yeast expression vector pPIC9.
      Two truncated forms of gD-1 were fitted with a His tail (designated as gD-1(1
      314His) and gD-1(1-254His)) to facilitate their purification. Large amounts of gD
      1(1-314) and gD-1(1-314His) (280-300mg/L induction medium) were produced. The
      yields of recombinant gD-1(1-254) and gD-1(1-254His) were lower: 20-36mg/L, and
      the yield of the gD-2(1-314) fragment was much lower: 6mg/L. SDS-PAGE analysis
      revealed multiple glycosylated species of the larger gD fragments, ranging in
      apparent molecular weight from 31 to 78kDa. The smaller gD-1(1-254) fragment
      appeared as two bands with molecular weights of 33 and 31kDa. All recombinant
      proteins produced by P. pastoris were recognized, as expected, by a panel of MAbs
      (A16, DL6, A18, DL11, HD1, ABDI, and AP7). In addition, we showed that gD-1(1
      314), gD-2(1-314), and gD-1(1-254His) were able to interfere with binding of HSV
      to susceptible cells. These results indicate that the conformations of the
      recombinant proteins closely resemble those of native gD.

PMID- 12182820
TI  - Design, production, and characterization of a monomeric streptavidin and its
      application for affinity purification of biotinylated proteins.
AB  - To expand the application of the streptavidin-biotin technology for reversible
      affinity purification of biotinylated proteins, a novel form of monomeric
      streptavidin was engineered and produced using Bacillus subtilis as the
      expression host. By changing as little as two amino acid residues (T90 and D128)
      to alanine, the resulting mutant streptavidin designated DM3 was produced 100% in
      the monomeric form as a soluble functional protein via secretion. It remained in
      the monomeric state in the presence or absence of biotin. Interaction of purified
      monomeric streptavidin with biotin was studied by surface plasmon resonance-based
      BIAcore biosensor. Its on-rate is comparable to that of monomeric avidin while
      its off-rate is seven times lower. The dissociation constant was determined to be
      1.3 x 10(-8)M. These properties make it an attractive agent for affinity
      purification of biotinylated proteins. An affinity matrix with immobilized DM3
      mutein was prepared and applied to purify biotinylated cytochrome c from a crude
      extract. Biotinylated cytochrome c could be purified to homogeneity in one step
      and was shown to retain full biological activity. Advantages of using DM3 mutein
      over other traditional methods in the purification of biotinylated proteins are
      discussed.

PMID- 12182821
TI  - Expression and purification of a small cytokine growth-blocking peptide from
      armyworm Pseudaletia separata by an optimized fermentation method using the
      methylotrophic yeast Pichia pastoris.
AB  - A small multifunctional cytokine, growth-blocking peptide (GBP), from the
      armyworm Pseudaletia separata larvae was expressed as a soluble and active
      recombinant peptide in the methylotrophic yeast Pichia pastoris. An expression
      vector for GBP secretion was constructed using vector pPIC9, and GBP was
      expressed under the control of the alcohol oxidase (AOX1) promoter. Although we
      first tried to cultivate GBP in shake flask cultures, the yield was low, probably
      due to proteolysis of the recombinant protein. To overcome this problem, we
      utilized a high-density fermentation method. The pH of the medium in the
      fermenter was kept at 3.0, and the medium was collected within 48h post methanol
      shift to minimize exposure of the target peptide to proteases. Recombinant GBP
      was purified through three reverse-phase HPLC columns. We characterized the 25
      amino acid GBP by molecular mass spectrometry and amino acid sequencing.
      Plasmatocyte spreading, one of the activities of GBP, was similar between
      chemically synthesized GBP and purified recombinant GBP. Up to 50mg GBP was
      recovered per 1L of yeast culture supernatant.

PMID- 12182822
TI  - A purification method of the diagnostic enzyme Bacillus uricase using magnetic
      beads and non-specific protease.
AB  - A simple purification method of the Bacillus uricase (Uao) was newly developed.
      The gene coding for Uao with a C-terminal 6-histidine tag (Uao-HT) was
      constructed and overexpressed. Using the non-specific proteases, such as
      proteinase K, the tag was easily removed because Uao-HT includes its C-terminal
      region to be specifically cleaved by them. Such treatment of Uao-HT with the
      proteases did not affect its enzymatic properties and enabled us to purify it
      from the crude extract with a single-step protocol; the cell lysate containing
      Uao-HT was mixed with the Ni ion-chelating magnetic beads and then the adsorbed
      enzyme was eluted with the proteinase K-containing buffer after untagged proteins
      were washed out. The isolated enzyme yielded a single band on SDS-PAGE and was
      fully active. This method is extremely useful for high-throughput purification of
      mutants because of compatibility with automation.

PMID- 12182823
TI  - Efficient expression and secretion of recombinant hirudin III in E. coli using
      the L-asparaginase II signal sequence.
AB  - One of the hirudin variants HV3 was efficiently expressed in Escherichia coli
      using the L-asparaginase II signal sequence and the product was secreted into the
      culture medium. For the secretory manufacture of HV3, the L-asparaginase II
      signal sequence containing a single NheI restriction site at its 3' end was
      designed using the degenerate codons and PCR-amplified from E. coli chromosomal
      DNA. The synthetic HV3 coding sequence was fused to the signal sequence in-frame
      by its 5' NheI restriction site. The above signal-HV3 fusion gene was inserted
      into an expression vector pTA, which was derived from pkk223-3 such that its
      expression was under the control of the tac promotor. The resulting HV3 secretion
      expression vector pTASH thus constructed was introduced into an E. coli host cell
      AS1.357 with high L-asparaginase II producing level. After inducing with IPTG,
      the expression product was efficiently secreted into the culture medium and shake
      flask culturing gave a yield of approximately 5 x 10(5)ATU/L (approximately
      60mg/L). The secreted HV3 was easily purified from culture supernatant using
      ultrafiltration, ion-exchange column chromatography, and FPLC reverse-phase
      chromatography. The purified rHV3 from the culture supernatant had the expected N
      terminal amino sequence and strong antithrombin activity, suggesting that the
      signal sequence was completely removed and the product was processed accurately
      during the secretion process.

PMID- 12182824
TI  - Cloning and hemolysin-mediated secretory expression of a codon-optimized
      synthetic human interleukin-6 gene in Escherichia coli.
AB  - Previously, we constructed human interleukin-6 (hIL-6)-secreting Escherichia coli
      and Salmonella typhimurium strains by fusion of the hIL-6 cDNA to the HlyA(s)
      secretional signal, utilizing the hemolysin export apparatus for extracellular
      delivery of a bioactive hIL-6-hemolysin (hIL-6-HlyA(s)) fusion protein. Molecular
      analysis of the secretion process revealed that low secretion levels were due to
      inefficient gene expression. To adapt the codon usage in hIL-6 cDNA to the E.
      coli codon bias, a synthetic hIL-6Ec gene variant was constructed from 20
      overlapping oligonucleotides, yielding a 561-bp fragment, which comprises the
      complete hIL-6 cDNA sequence. Genetic fusion of the hIL-6Ec gene with the hlyA(s)
      secretional signal as an integral part of the hemolysin operon resulted in 3-fold
      higher hIL-6-HlyA(s) secretion levels in E. coli, compared to a strain expressing
      the original hIL-6-hlyA(s) fusion gene. An increase in the electrophoretic
      mobility of secreted hIL-6-HlyA(s) in non-reducing SDS-PAGE, similar to that
      found for recombinant mature hIL-6, and the absence of such a mobility shift in
      the intracellular hIL-6-HlyA(s) protein fraction indicated that in hIL-6-HlyA(s)
      most probably correct intramolecular disulfide bond formation occurred during the
      secretion step. To confirm the disulfide bond formation, hIL-6-HlyA(s) was
      purified by a single-step immunoaffinity chromatography from culture supernatant
      in yields of 18 microg/L culture supernatant with purity in the range of 60%.
      These results demonstrate that codon usage has an impact on the hemolysin
      mediated secretion of hIL-6 and, furthermore, provide evidence that the hemolysin
      system enables secretory delivery of disulfide-bridged proteins.

PMID- 12182825
TI  - Large-scale production of functional human adrenomedullin: expression, cleavage,
      amidation, and purification.
AB  - Human adrenomedullin (hAM) is a 52-amino-acid regulatory peptide containing a six
      membered ring structure and an amidated C-terminus, features that are essential
      for its biological activity. Here, we describe a simple and effective protocol
      for producing large quantities of highly pure, functional recombinant hAM. A
      peptide precursor (hAM-Gly) was expressed in Escherichia coli as a fusion protein
      with thioredoxin and collected as inclusion bodies. The fusion protein was then
      digested with BLase, a glutamate-specific endopeptidase, to prepare hAM-Gly. The
      essential ring structure formed spontaneously, while the terminal amide was
      generated by conversion of the added glycine residue using peptidylglycine alpha
      amidating enzyme. The low solubility of hAM-Gly enabled the use of a selective
      precipitation/extraction method to generate a product that was 80-90% pure, which
      was sufficient to proceed with the alpha-amidating enzyme reaction. The resultant
      hAM was then purified further by column chromatography. The final yield was about
      82 mg/L of bacterial culture, and the purity, determined by reverse phase HPLC,
      was >99.5%. The recombinant hAM was biologically active, eliciting concentration
      dependent increases in cAMP in CHO-K1 cells expressing a specific hAM receptor
      and hypotensive responses when intravenously injected into rats. This new
      approach to the synthesis of hAM is simpler and more cost-effective for large
      scale production than chemical synthesis. It therefore represents a new powerful
      tool that has the potential to facilitate analysis of the structure and function
      of hAM, as well as the development of new therapeutic protocols for the treatment
      of ailments such as hypertension.

PMID- 12182827
TI  - Purification of secreted leukotoxin (LtxA) from Actinobacillus
      actinomycetemcomitans.
AB  - The RTX (repeats in toxin) family of toxins is important in the pathogenesis of
      many Gram-negative bacteria. The oral and systemic human pathogen Actinobacillus
      actinomycetemcomitans produces a member of this family known as leukotoxin
      (LtxA). Previously, we found that LtxA is secreted into culture supernatants of
      A. actinomycetemcomitans and that this protein is abundant and relatively pure.
      Here, we report a large-scale method for the isolation and purification of LtxA
      from culture supernatants of A. actinomycetemcomitans strain JP2. The
      purification scheme involves ammonium sulfate precipitation of culture
      supernatants, dialysis, and ultrafiltration to concentrate LtxA to approximately
      10mg/ml. We found that LtxA remained soluble in buffer that contained at least
      250mM NaCl. Purified LtxA was >98% pure and the final preparations were active
      against HL-60 cells. The entire purification protocol can be completed within 2
      days. The ability to readily obtain a large amount of purified leukotoxin should
      accelerate investigations into the structure and biology of this important
      virulence factor.

PMID- 12182826
TI  - Preparation and expression of biologically active prolactin and growth hormone
      receptors and suppressor of cytokine signaling proteins 1, 2, 3, and 6 tagged
      with cyan and yellow fluorescent proteins.
AB  - To prepare reagents for a study of the interactions of prolactin (PRL) and growth
      hormone (GH) receptors (Rs) with suppressor of cytokine signaling (SOCS) proteins
      in living cells by fluorescence resonance energy transfer methodology, the
      respective proteins were tagged with cyan (CFP) or yellow (YFP) fluorescent
      protein. Constructs encoding ovine (o)PRLR-YFP, oPRLR-CFP, oGHR-YFP, and oGHR-CFP
      tagged downstream of the receptor DNA were prepared in the plasmid pcDNA plasmid
      and tested for biological activity in HEK 293T cells transiently cotransfected
      with those constructs and the reporter gene encoding luciferase. All four
      constructs were biologically active and as potent as their untagged counterparts.
      Cells transfected with those proteins exhibited fluorescence in the cytoplasm and
      the membrane. Constructs encoding DNA tagged with YFP or CFP upstream of SOCS1,
      SOCS2, SOCS3, and SOCS6 were prepared in pECFP-C1 and pEYFP-C1 plasmids. The
      biological activities of SOCS1 and SOCS3 tagged at their amino termini were
      assayed by their ability to inhibit placental lactogen (PL)- or GH-induced
      activation of JAK2/STAT5-mediated luciferase transcription in HEK 293T cells; the
      activity of SOCS2 was assayed by its ability to abolish SOCS1-induced inhibition.
      The tagged proteins exhibited biological activity that was equal to or even more
      potent than their untagged counterparts. The biological activities of CFP-SOCS2
      and YFP-SOCS2 were also assayed using GST-GHR binding assay. Their interaction
      with the cytosolic domain of GHR was equivalent to their respective untagged
      counterparts. The biological activity of the construct encoding SOCS6 was not
      tested because of lack of a suitable assay. Cells transfected with eight of these
      tagged constructs expressed the fluorescent proteins in both the nucleus and
      cytosol; the tagged SOCS2 was localized mostly in the latter compartment.

PMID- 12182828
TI  - Expression and one-step purification of a developmentally regulated protein from
      Dictyostelium discoideum.
AB  - To overexpress Dictyostelium 5NT, a 1506bp fragment of the cDNA encoding the gene
      was cloned into a pET32c+ vector and expressed in the Escherichia coli expression
      host BL21-CodonPlus(DE3)-RIL by Isopropyl-beta-D-thiogalactoside (IPTG)
      induction. Maximum induction of insoluble recombinant protein was reached after
      incubation of the culture for 3h with 1.0mM IPTG. High level of 5NT expression
      was confirmed by SDS-PAGE and immunoblotting analysis. The recombinant 5NT was
      purified to homogeneity by a one-step purification using continuous-elution
      electrophoresis. Ten mg recombinant 5NT was purified per liter of growth medium.
      To achieve one of the goals of this study, polyclonal antibody against the
      recombinant 5NT was produced in a rabbit. We have shown previously by Northern
      blot and reporter gene analyses that 5nt is developmentally regulated. In this
      report, we used polyclonal antibody against the recombinant protein in Western
      blot analysis of membrane protein extracts from different developmental stages of
      Dictyostelium. The 5NT protein levels were first detected at the tight
      aggregation stage of development. Thus, there is no significant delay between
      transcription and translation of 5nt.

PMID- 12182829
TI  - Synthesis of cholera toxin B subunit gene: cloning and expression of a functional
      6XHis-tagged protein in Escherichia coli.
AB  - Cholera toxin B subunit (CTB) has been extensively studied as immunogen,
      adjuvant, and oral tolerance inductor depending on the antigen conjugated or
      coadministered. It has been already expressed in several bacterial and yeast
      systems. In this study, we synthesized a versatile gene coding a 6XHis-tagged CTB
      (359bp). The sequence was designed according to codon usage of Escherichia coli,
      Lactobacillus casei, and Salmonella typhimurium. The gene assembly was based on a
      polymerase chain reaction, in which the polymerase extends DNA fragments from a
      pool of overlapping oligonucleotides. The synthetic gene was amplified, cloned,
      and expressed in E. coli in an insoluble form, reaching levels about 13 mg of
      purified active pentameric rCTB per liter of induced culture. Western blot and
      ELISA analyses showed that recombinant CTB is strongly and specifically
      recognized by polyclonal antibodies against the cholera toxin. The ability to
      form the functional pentamers was observed in cell culture by the inhibition of
      cholera toxin activity on Y1 adrenal cells in the presence of recombinant CTB.
      The 6XHis-tagged CTB provides a simple way to obtain functional CTB through
      Ni(2+)-charged resin after refolding and also free of possible CTA contaminants
      as in the case of CTB obtained from Vibrio cholerae cultures.

PMID- 12182830
TI  - Secretory expression and purification of Aspergillus niger glucose oxidase in
      Saccharomyces cerevisiae mutant deficient in PMR1 gene.
AB  - The gene encoding glucose oxidase (GOD) from Aspergillus niger was expressed as a
      secretory product in the yeast Saccharomyces cerevisiae. Six consecutive
      histidine residues were fused to the C-terminus of GOD to facilitate
      purification. The recombinant GOD-His(6) secreted by S. cerevisiae migrated as a
      broad diffuse band on SDS-PAGE, with an apparent molecular weight higher than
      that in natural A. niger GOD. To investigate the effects of hyperglycosylation on
      the secretion efficiency and enzyme properties, GOD-His(6) was expressed and
      secreted in a S. cerevisiae mutant in which the PMR1 gene encoding Ca(++)-ATPase
      was disrupted. The pmr1 null mutant strain secreted an amount of GOD-His(6) per
      unit cell mass higher than that in the wild-type strain. In contrast to the
      hyperglycosylated GOD-His(6) secreted in the wild-type strain, the pmr1 mutant
      strain secreted GOD-His(6) in a homogeneous form with a protein band pattern
      similar to that in natural A. niger GOD, based on SDS-PAGE. The hyperglycosylated
      and pmr1Delta mutant-derived GOD-His(6) enzymes were purified to homogeneity by
      immobilized metal ion-affinity chromatography and their specific activities and
      stabilities were compared. The specific activity of the pmr1Delta mutant-derived
      GOD-His(6) on a protein basis was very similar to that of the hyperglycosylated
      GOD-His(6), although its pH and thermal stabilities were lower than those of the
      hyperglycosylated GOD-His(6).

PMID- 12182831
TI  - Large-scale purification of active platelet integrin glycoprotein IIb-IIIa.
AB  - Glycoprotein IIb-IIIa is an abundant platelet receptor of the integrin family
      that plays a primary role in platelet aggregation. It exists on the platelet
      surface predominantly in a resting or inactive conformation that is converted to
      an active binding competent conformation upon platelet activation. There is much
      interest in studying the difference between active and inactive GP IIb-IIIa,
      developing therapeutic agents targeted towards GP IIb-IIIa and developing
      diagnostic assays for antibodies that recognize epitopes on GP IIb-IIIa. We
      present here the development of a large-scale process for purifying active GP IIb
      IIIa from human platelets. The procedure results in 25mg batch sizes of high
      purity and activity. Additionally, the effects of detergent concentration and
      impurities such as IgG on ELISA assays are examined.

PMID- 12182832
TI  - Removal of DnaK contamination during fusion protein purifications.
AB  - The use of fusion proteins for recombinant protein expression in Escherichia coli
      has become popular because the carrier increases protein solubility, standardizes
      expression levels, and facilitates purification of the fusion products. However,
      we have observed that the peptide regions that fuse the carrier to the protein of
      interest bind E. coli Hsp70 molecular chaperones (DnaK) depending on their amino
      acid composition, resulting in an unwanted contamination during protein
      purification. Here we describe an approach that helps to circumvent this unwanted
      contamination. First, the appropriate amino acids surrounding and comprising the
      cloning site are chosen by using a software based on an algorithm already
      developed to decrease to a minimum the propensity of the fusion protein to bind
      DnaK. Second, DnaK contamination is significantly reduced by washing the fusion
      protein bound to the purification resin with MgATP plus soluble denatured E. coli
      proteins before elution. The approach can also be applied to eliminate other
      molecular chaperones.

PMID- 12182833
TI  - Overexpression, purification, and characterization of the periplasmic space
      thiamin-binding protein of the thiamin traffic ATPase in Escherichia coli.
AB  - Thiamin (Vitamin B(1)) transport in Escherichia coli occurs by the superfamily of
      traffic ATPases in which the initial receptor is the periplasmic binding protein.
      We have cloned the periplasmic thiamin-binding protein (TBP) of the E. coli
      periplasmic thiamin transport system and purified the overexpressed protein to
      apparent homogeneity. A subsequent biochemical characterization demonstrates that
      TBP is a 34.205kDa monomer. TBP also contains one tightly bound thiamin species
      [thiamin, thiamin monophosphate (TMP), or thiamin diphosphate (TDP)] per monomer
      (K(D)=0.8 microM) when isolated under conditions that would remove any loosely
      bound ligands. We also demonstrate that thiamin is readily exchangeable in the
      presence of exogenous thiamin with a k(off)=0.12s(-1). The biochemical
      characteristics of the overexpressed, plasmid-derived TBP are indistinguishable
      from those determined for endogenous TBP purified from E. coli. The
      overexpression and purification of TBP that we present here allows the rapid
      isolation of large amounts of pure protein that are required for further
      mechanistic and structural studies and demonstrates a vast improvement over
      previously reported purifications.

PMID- 12182834
TI  - Expression, purification, and characterization of recombinant nonphosphorylating
      NADP-dependent glyceraldehyde-3-phosphate dehydrogenase from Clostridium
      acetobutylicum.
AB  - Clostridium acetobutylicum gapN was cloned and expressed in Escherichia coli BL
      21. The IPTG-induced nonphosphorylating NADP-dependent GAPDH (GAPN) has been
      purified about 34-fold from E. coli cells and its physical and kinetic properties
      were investigated. The purification method consisted of a rapid and
      straightforward procedure involving anion-exchange and hydroxyapatite
      chromatographies. The purified protein is an homotetrameric of 204kDa exhibiting
      absolute specificity for NADP. Chromatofocusing analysis showed the presence of
      only one acidic GAPN isoform with an acid isoelectric point of 4.2. The optimum
      pH of purified enzyme was 8.2. Studies on the effect of assay temperature on
      enzyme activity revealed an optimal value of about 65 degrees C with activation
      energy of 18KJmol(-1). The apparent K(m) values for NADP and D-glyceraldehyde-3
      phosphate (D-G3P) or DL-G3P were estimated to be 0.200+/-0.05 and 0.545+/-0.1 mM,
      respectively. No inhibition was observed with L-D3P. The V(max) of the purified
      protein was estimated to be 78.8 U mg(-1). The Cl. acetobutylicum GAPN was
      markedly inhibited by sulfhydryl-modifying reagent iodoacetamide, these results
      suggest the participation of essential sulfhydryl groups in the catalytic
      activity.

PMID- 12182835
TI  - Expression, purification, and characterization of human dipeptidyl peptidase
      IV/CD26 in Sf9 insect cells.
AB  - The human dipeptidyl peptidase IV/CD26 (DPPIV/CD26) is a multifunctional type-II
      membrane bound glycoprotein. As a receptor of collagen I and fibronectin it
      mediates cell-cell and cell-matrix adhesion, and by interacting with
      extracellular adenosine deaminase and CD45 it is involved in regulatory and
      costimulatory events in the immune system. DPPIV/CD26 has a very distinct
      substrate specificity, and is potentially capable of truncating many cytokines,
      chemokines, and peptide hormones. In this study, we describe the overexpression,
      purification, and characterization of human DPPIV/CD26 in Spodoptera frugiperda
      (Sf9) cells, using the baculovirus system. Overexpression of DPPIV/CD26 was
      confirmed by measurement of its peptidase specificity, SDS-PAGE, and Western blot
      analyses. Expression rates were between 6.4 and 17.6 mg protein per liter
      suspension culture (1.5 x 10(9)cells). The N-linked oligosaccharide composition
      was examined and compared with that of mammalian cell-expressed DPPIV/CD26. Two
      step purification by immunoaffinity chromatography and size-exclusion fast
      protein liquid chromatography (SE-FPLC) led to highly stable protein with
      significant peptidase activity. A subsequent gel filtration step on a Superdex
      200 column yielded 2mg homogeneous dimeric DPPIV/CD26 (per liter insect cell
      culture) for crystallographic studies. Protein homogeneity was confirmed by
      silver staining of non-denaturating PAGE gels and by MALDI-TOF analysis of
      tryptic peptides.

PMID- 12182836
TI  - Expression, purification, and biochemical characterization of Mycobacterium
      tuberculosis aspartate decarboxylase, PanD.
AB  - Like all bacteria, Mycobacterium tuberculosis (Mtb) possesses the genes necessary
      for coenzyme A biosynthesis and metabolism. In the present work, the Mtb panD
      gene was PCR amplified, overexpressed, and purified by metal affinity
      chromatography. The recombinant Mtb panD was found to exist as a tetramer in
      solution. Incubation of Mtb panD at 37 degrees C for several hours resulted in a
      complete cleavage of the inactive (pi) form into the two subunits (alpha and
      beta). The cleavage was confirmed by Western blot analysis as well as by N
      terminal sequencing. Cleaved Mtb panD was assayed for decarboxylase activity with
      L-aspartate as substrate. The kinetic parameters K(m) and k(cat) were found to be
      219 microM and 0.65s(-1), respectively. These results provide the means for
      further studies based on the identification of the Mtb panD as well as other
      components of pantothenate metabolism as potential drug targets.

PMID- 12182837
TI  - Preparation of active recombinant cathepsin K expressed in bacteria as inclusion
      body.
AB  - Human cathepsin K (EC 3.4.22.38) is a member of the cysteine protease family with
      high primary sequence homology to cathepsins S, L, and B. It has been shown that
      cathepsin K plays a major role in the resorption of the bone matrix by
      osteoclasts. Cathepsin K has a potential as a drug target for the diseases
      related to bone matrix metabolism such as osteoporosis. We have expressed
      recombinant human procathepsin K in Escherichia coli as inclusion bodies.
      Purified procathepsin K had size of 38kDa which is in agreement with the
      predicted mass of the construct. Refolding was done by rapid dilution into 50mM
      Tris-HCl, pH 8.0 buffer containing 5mM EDTA, 10 mM GSH, 1mM GSSG, 0.7 M L
      arginine, 0.5 M NaCl, and 1% CHAPS and further dialysis against 25 mM Tris-HCl,
      pH 8.0 containing 0.5 M NaCl. Mature active cathepsin K was prepared from
      refolded procathepsin K by incubating at 40 degrees C in pH 4.0 buffers with or
      without pepsin or cysteine. The presence of pepsin or cysteine in autocatalysis
      buffer did not have effect on the degree of conversion of nascent to mature
      cathepsin K, but reduced the autocatalysis time slightly. Proteolytic activity
      was confirmed using synthetic substrate, and Western blotting identified mature
      cathepsin K. Active cathepsin K had type I and II collagenolytic activities which
      could be inhibited by E-64.

PMID- 12182838
TI  - Heterologous expression, purification, and enzymatic activity of Mycobacterium
      tuberculosis NAD(+) synthetase.
AB  - The enzyme NAD(+) synthetase (NadE) catalyzes the last step of NAD biosynthesis.
      Given NAD vital role in cell metabolism, the enzyme represents a valid target for
      the development of new antimycobacterial agents. In the present study we
      expressed and purified two putative forms of Mycobacterium tuberculosis NAD(+)
      synthetase, differing in the polypeptide chain length (NadE-738 and NadE-679).
      Furthermore, we evaluated several systems for the heterologous expression and
      large scale purification of the enzyme. In particular, we compared the efficiency
      of production, the yield of purification, and the catalytic activity of
      recombinant enzyme in different hosts, ranging from Escherichia coli strains to
      cultured High Five (Trichoplusia ni BTI-TN-5B1-4) insect cells. Among the systems
      assayed, we found that the expression of a thioredoxin-NadE fusion protein in E.
      coli Origami(DE3) is the best system in obtaining highly pure, active NAD(+)
      synthetase. The recombinant enzyme maintained its activity even after proteolytic
      cleavage of thioredoxin moiety. Biochemical evidence suggests that the shorter
      form (NadE-679) may be the real M. tuberculosis NAD(+) synthetase. These results
      enable us to obtain a purified product for structure-function analysis and high
      throughput assays for rapid screening of compounds which inhibit enzymatic
      activity.

PMID- 12182839
TI  - Human cerebral endothelial cells are a potential source for bioactive BDNF.
AB  - Inflammatory stimuli within the central nervous system may not only induce tissue
      damage but may also convey neuroprotection. It has been shown that brain derived
      neurotrophic factor (BDNF) is a neuroprotective candidate. Here we show that BDNF
      is constitutively expressed in cultured human cerebral endothelial cells (HCEC)
      and can further be upregulated under proinflammatory conditions. TNF-alpha
      treatment resulted in an increase in BDNF mRNA expression and protein levels were
      significantly elevated after 72 h (69+/-33%, P<0.01). Using functional assays it
      was demonstrated that BDNF produced by HCEC is bioactive and supports motoneuron
      survival. In contrast, BDNF expression was reduced by TNF-alpha in human
      umbilical vein endothelial cells (HUVEC). We conclude that HCEC likely to
      contribute to neuronal survival under physiological and inflammatory conditions.

PMID- 12182840
TI  - Local levels of interleukin-1beta, -4, -6 and tumor necrosis factor alpha in an
      experimental model of murine osteomyelitis due to staphylococcus aureus.
AB  - The purpose of this study is to evaluate local levels of interleukin-1 beta (IL-1
      beta), -4 (IL-4), -6 (IL-6), and tumour necrosis factor-alpha (TNF-alpha), in a
      model of murine osteomyelitis due to Staphylococcus aureus. Cytokine levels in
      supernatants derived from bone homogenates were determined by enzyme-linked
      immunosorbent assay, for 28 days following the direct implantation of murine
      tibiae with S.aureus. Levels of IL-1 beta and IL-6 in infected bone were elevated
      in the early post-infection period and then decreased. In contrast, TNF-alpha
      levels remained elevated 3 to 28 days post-infection, while IL-4 levels were
      elevated late in the course of infection. The histopathology of infected bone
      showed predominant infiltration of inflammatory cells and bone resorption 3 to 7
      days after infection, and bone resorption and adjacent areas of formation 14 to
      28 days after infection. These results suggest that the elevated IL-1 beta and IL
      6 levels induced by infection may be related to bone damage mainly in the early
      phase of infection, and that TNF-alpha and IL-4 may at least in part be
      associated with histopathological changes, including both bone resorption and
      formation in the later phase of this osteomyelitis model.

PMID- 12182841
TI  - Regulation of proteinase-activated receptor 1 by inflammatory mediators in human
      vascular endothelial cells.
AB  - Thrombin plays a critical role in haemostasis, inflammation, and cell
      proliferation, mediated by proteinase-activated receptor 1 (PAR-1; thrombin
      receptor). The physiological and pathological regulation of PAR-1 by inflammatory
      mediators has not yet been fully elucidated. The aim of this study is to
      investigate the effects of inflammatory mediators on mRNA and protein expression
      of PAR-1 in early passage human vascular endothelial cells. Endothelial cells
      were activated by inflammatory mediators, such as tumour necrosis factor alpha
      (TNFalpha), interferon gamma (IFN gamma), and bacterial substance
      lipopolysaccharide (LPS), and the PAR-1 expression was verified by flow cytometry
      or RT-PCR. By stimulating endothelial cells with TNFalpha, IFN gamma, and LPS,
      the PAR-1 expression on the cell surface remained almost unchanged for 48 h.
      After stimulation with 20-300 U/ml TNFalpha, the total cellular PAR-1 expression
      (both on cell surface and in the cytoplasm) significantly decreased at 24h and
      thereafter recovered to the basal level at 48 h. The stimulation with 100 U/ml
      TNFalpha transiently down-regulated the PAR-1 mRNA expression to approximately
      0.3-fold of the basal level at 30 min, but it rebounded 3-fold above the basal
      level at 6h, and again decreased to 0.5-fold of the basal level at 12h, and
      finally returned to the basal level at 24h. In contrast, IFN gamma or LPS did not
      affect the PAR-1 mRNA expression.

PMID- 12182842
TI  - Interleukin-12 inhibits eotaxin secretion of cultured primary lung cells and
      alleviates airway inflammation in vivo.
AB  - The mechanisms that cause the inflammation of airway and lung tissue in asthma
      have been studied extensively. It is noted that type 1T helper cell (Th1)-related
      cytokines could decrease the accumulation of eosinophils in lung tissue and
      relieve airway constriction. But the therapeutic mechanisms of Th1 cytokines
      remain unclear. In this study, interleukin-12 (IL-12) DNA plasmid as a
      therapeutic reagent was delivered intravenously. Bronchoalveolar lavage (BAL)
      fluids were collected from IL-12 treated and control mice, and analyzed for cell
      composition and eotaxin level. The results showed that IL-12 DNA plasmid could
      effectively inhibit eosinophilia and airway inflammation in vivo. The level of
      eotaxin in BAL fluid also decreased. To further investigate the effect of Th1
      related cytokines such as IL-12 or interferon-gamma (IFN-gamma) on the eotaxin
      level produced by lung cells, primary lung cell culture was established. The
      results demonstrated that both IL-12 and IFN-gamma could suppress eotaxin
      secretion from IL-13 or IL-4 stimulated primary lung cell culture. Moreover, the
      inhibitory effect of IL-12 could not be reversed by the administration of anti
      IFN-gamma antibody. All the evidences suggested that IL-12 could regulate airway
      inflammation by suppressing the eotaxin secretion of lung tissue through an IFN
      gamma independent mechanism.

PMID- 12182843
TI  - Cytokine production in Linomide-treated nod mice and the potential role of a Th
      (1)/Th(2) shift on autoimmune and anti-inflammatory processes.
AB  - Linomide prevents the development of autoimmune insulitis and insulin-deficient
      diabetes mellitus in female NOD mice. Linomide prevents development of autoimmune
      manifestations in other experimentally induced and spontaneous autoimmune
      diseases as well, but the mechanism of action is unknown. The present report
      summarizes our investigations on the effect of Linomide on different functional T
      cell subsets in NOD mice analyzed according to their cytokine profile.
      Supernatants from cultured splenocytes and peritoneal cells taken from Linomide
      treated mice contained lower levels of TNFalpha, IL-1 beta, IFN gamma and IL-12
      versus higher levels of IL-4, IL-6 and IL-10 in comparison with supernatants from
      cultures of untreated mice. Our results suggest that regulation of autoimmunity
      following oral Linomide administration in NOD mice induces a shift from Th(1) to
      Th(2) phenotype response, thereby preventing the development of diabetes by
      active cytokine-induced immunoregulation of T cell subsets, including
      downregulation of Th(1) and upregulation of Th(2).

PMID- 12182844
TI  - Crouzon's syndrome: differential in vitro secretion of bFGF, TGFbeta I isoforms
      and extracellular matrix macromolecules in patients with FGFR2 gene mutation.
AB  - In the Crouzon's syndrome the cranial morphogenic processes are altered due to
      the early fusion of cranial sutures. We analysed the phenotype of cultured
      fibroblasts from normal subjects and from Crouzon patients with a specific
      fibroblast growth factor receptor 2 mutation resulting in a Cys 342 Tyr
      substitution within the third immunoglobulin domain. Crouzon fibroblasts differed
      from normal fibroblasts in their extracellular matrix macromolecule accumulation.
      In Crouzon fibroblasts glycosaminoglycans and fibronectin were decreased and type
      I collagen increased. As transforming growth factors beta (TGF beta) and basic
      fibroblasts growth factor (bFGF) together regulate extracellular matrix
      deposition, we evaluated TGF beta(1), TGF beta(3) and bFGF production by Crouzon
      and normal fibroblasts. TGF beta(1), TGFb(3) and bFGF levels were lower while TGF
      beta(1) mRNA transcripts were higher in Crouzon cells. As the increased TGF
      beta(1) gene expression did not translate into a parallel increase of secreted
      TGF beta(1), control of TGF beta(1) secretion may be mainly post-transcriptional.
      Furthermore, adding bFGF increased TGF beta(1) and TGF beta(3) secretion,
      suggesting the drop may be due to the altered signal transduction of bFGF. These
      innovative data suggest the in vitro differences between normal and Crouzon
      fibroblasts may be due to an imbalance in TGF beta and bFGF levels which alters
      the microenvironment where morphogenesis takes place.

PMID- 12182845
TI  - Increase in serum level of interleukin-1 alpha mediates morphine anti
      inflammatory effect in carrageenan-induced paw oedema in mice.
AB  - In the present studies we examined the effects of an intra-peritoneal injection
      of morphine (7 mg/kg) on carrageenan-induced paw oedema in mice. Carrageenan
      induced paw oedema was measured by mercury plethysmometer and was maximal at hour
      3, and pretreatment with morphine could reduce the oedema significantly. At the
      same time the serum levels of interleukin-1 alpha (IL-1 alpha) were increased.
      Pretreatment with naloxone and dexamethasone abolished morphine anti-inflammatory
      while decreasing IL-1 alpha serum levels, significantly. These findings suggest
      that an increase in serum levels of IL-1 alpha plays an important role in the
      anti-inflammatory effect of morphine.

PMID- 12182847
TI  - Peptide inhibitors of CDK2-cyclin A that target the cyclin recruitment-site:
      structural variants of the C-terminal Phe.
AB  - A focused series of octapeptides based on the lead compound H-His-Ala-Lys-Arg-Arg
      Leu-Ile-Phe-NH(2) 1, in which the C-terminal phenylalanine residue was replaced
      by alpha and/or beta-modified variants, was synthesized using solid-phase
      chemistry. Both the L-threo-beta-hydroxy-phenylalanine (beta-phenylserine, Pse)
      and (2S)-phenylalaninol derivatives, as competitive binders at the cyclin
      recruitment site, displayed potent inhibitory activity towards the CDK2-cyclin A
      complex. Unexpectedly, the D-threo-Pse derivatives also showed inhibitory
      activity.

PMID- 12182848
TI  - Synthesis of tag introducible (3-trifluoromethyl)phenyldiazirine based
      photoreactive phenylalanine.
AB  - An efficient synthesis of tag introducible (3-trifluoromethyl)phenyldiazirine
      based phenylalanine derivatives is described. Alkylation of a chiral glycine
      equivalent with a spacer containing (3-trifluoromethyl)phenyldiazirinyl bromides
      enables us to create photoreactive L-phenylalanine derivatives. After
      introduction of biotin at the spacer, the biotinylated and photoreactive amino
      acid was applied for L-amino acid oxidase and incorporated into a substrate
      binding site. These compounds will be powerful tools not only for photoaffinity
      labeling to elucidate properties of bioactive peptides but also as trifunctional
      photophors to introduce a ligand skeleton.

PMID- 12182849
TI  - Synthesis and antiaggregant properties of Stabilized analogues of polyunsaturated
      fatty acid metabolites.
AB  - New aromatic and heteroaromatic analogues of polyunsaturated fatty acid
      metabolites have been prepared using short and versatile strategies. Preliminary
      studies of their activity as inhibitors of platelet aggregation are reported.

PMID- 12182850
TI  - Spirocyclic NK(1) antagonists I: [4.5] and [5.5]-spiroketals.
AB  - A series of novel spiroketal-based NK(1) antagonists is described. The effect of
      modifications to the spiroether ring and aromatic substituents are discussed,
      leading to the identification of compounds with high affinity and excellent CNS
      penetration.

PMID- 12182851
TI  - Parallel solution- and solid-phase synthesis of spirohydantoin derivatives as
      neurokinin-1 receptor ligands.
AB  - The combination of the 3,5-bis(trifluoromethyl)phenyl group with a spirohydantoin
      motive as a central scaffold was the basis for the design of a combinatorial
      library targeted towards the neurokinin-1 receptor. A solution- and solid-phase
      procedure is described and binding affinities of representative compounds
      presented.

PMID- 12182852
TI  - Halogenated indole-3-acetic acids as oxidatively activated prodrugs with
      potential for targeted cancer therapy.
AB  - Substituted indole-3-acetic acid (IAA) derivatives, plant auxins with potential
      for use as prodrugs in enzyme-prodrug directed cancer therapies, were oxidised
      with horseradish peroxidase (HRP) and toxicity against V79 Chinese hamster lung
      fibroblasts was determined. Rate constants for oxidation by HRP compound I were
      also measured. Halogenated IAAs were found to be the most cytotoxic, with typical
      surviving fractions of <10(-3) after incubation for 2h with 100 microM prodrug
      and HRP.

PMID- 12182853
TI  - Perylene diimides with different side chains are selective in inducing different
      G-quadruplex DNA structures and in inhibiting telomerase.
AB  - Four N,N'-disubstituted perylene diimides, having different side chains, have
      been studied for their ability in inducing G-quadruplex DNA structures. We found
      that electrostatic interactions between ligands side chains and DNA grooves play
      a main role not only in the amount of G-quadruplex formed, but also in selecting
      its topology. Moreover, such compounds show also a different ability to inhibit
      telomerase. The correlation of these findings suggests the intriguing possibility
      that different G-quadruplex structures could differently inhibit the enzyme.

PMID- 12182854
TI  - A new series of M3 muscarinic antagonists based on the 4-amino-piperidine
      scaffold.
AB  - A series of 4-amino-piperidine containing molecules have been synthesized and
      structure-affinity relationship toward the M3-muscarinic receptor has been
      investigated. Chemical modulations provided molecules with K(i) for the human M3
      R up to 1 nM with variable selectivity (3- to 40-fold) over the human M2-R.
      Compounds 2 (pA(2)=8.3, 8.6) demonstrates in vitro on guinea pig bladder and
      ileal strips potent anticholinergic properties and tissue selectivity.

PMID- 12182855
TI  - New N-alkyl-1,2-dihydro-2-thioxo-3-pyridinecarbothioamides as antituberculous
      agents with improved pharmacokinetics.
AB  - Infections caused by multidrug-resistant Mycobacterium tuberculosis (MT) and non
      tuberculous mycobacteria are difficult to treat and, indeed, new therapeutic
      agents are being sought. As a part of an ongoing research in our laboratories,
      novel N-alkyl-1,2-dihydro-2-thioxo-3-pyridinecarbothioamides have been
      synthesized and evaluated against several strains of MT and Mycobacterium avium
      complex (MAC). The pharmacokinetics and relative bioavailability after
      intravenous administration of three derivatives have been investigated.
      Introduction of a hydroxyl or a tertiary amino group in the N-alkyl chain
      resulted in an improved pharmacokinetic profile without affecting sensitively the
      antituberculous potency.

PMID- 12182856
TI  - Novel phenolic antioxidants as multifunctional inhibitors of inducible VCAM-1
      expression for use in atherosclerosis.
AB  - A series of novel phenolic compounds has been discovered as potent inhibitors of
      TNF-alpha-inducible expression of vascular cell adhesion molecule-1 (VCAM-1) with
      concurrent antioxidant and lipid-modulating properties. Optimization of these
      multifunctional agents led to the identification of 3a (AGI-1067) as a clinical
      candidate with demonstrated efficacies in animal models of atherosclerosis and
      hyperlipidemia.

PMID- 12182857
TI  - Tetrahydrothienopyridylbutyl-tetrahydrobenzindoles: new selective ligands of the
      5-HT(7) receptor.
AB  - The synthesis and the affinity for the 5-HT(7) receptor and other receptors of a
      novel series of fused-ring tetrahydropyridine derivatives are described. Some of
      the compounds showed high affinity for the 5-HT(7) receptor.
      Tetrahydrothienopyridylbutyl-tetrahydrobenzindoles and are potent ligands for the
      5-HT(7) receptor, with high selectivity over the 5-HT(2) receptor and other
      receptors. These compounds should be useful tools for clarifying the biological
      role of the 5-HT(7) receptor.

PMID- 12182858
TI  - Glutathione-like tripeptides as inhibitors of glutathionylspermidine synthetase.
      Part 1: Substitution of the glycine carboxylic acid group.
AB  - Glutathionylspermidine synthetase/amidase (GspS) is an essential enzyme in the
      biosynthesis and turnover of trypanothione and represents an attractive target
      for the design of selective anti-parasitic drugs. We synthesised a series of
      analogues of glutathione (L-gamma-Glu-L-Leu-Gly-X) where the glycine carboxylic
      acid group (X) has been substituted for other acidic groups such as tetrazole,
      hydroxamic acid, acylsulphonamide and boronic acid. The boronic acid appears the
      most promising lead compound (IC(50) of 17.2 microM).

PMID- 12182859
TI  - Silica-based artificial protease exploiting aldehyde groups as catalytic
      elements.
AB  - An artificial protease synthesized by covering the surface of silica gel with
      aldehyde and indole groups effectively hydrolyzed albumin and gamma-globulin. It
      is proposed that the aldehyde group is involved in both complexation of the
      protein substrate and the catalytic cleavage of the peptide bonds of the
      complexed proteins.

PMID- 12182860
TI  - Dihydroquinolines as novel n-NOS inhibitors.
AB  - Dihydroquinolines have been synthesized and have been shown to be potent n-NOS
      inhibitors. Selectivity versus e-NOS was increased to approximately 100-fold
      through appropriate substitution at the benzene ring.

PMID- 12182861
TI  - Quaternary salts of E2020 analogues as acetylcholinesterase inhibitors for the
      reversal of neuromuscular block.
AB  - A series benzylpiperidinium and benzylpyridinium quaternary salts have been
      synthesised and tested for inhibition of acetylcholinesterase and reversal of
      neuromuscular block induced by vecuronium. Several potent reversal agents have
      been identified and their haemodynamic effects measured.

PMID- 12182862
TI  - Novel piperidinium and pyridinium agents as water-soluble acetylcholinesterase
      inhibitors for the reversal of neuromuscular blockade.
AB  - A series of piperidinium and pyridinium agents containing a common structural
      fragment of 5,6-dimethoxybenzothiophene have been synthesised as water-soluble
      acetylcholinesterase inhibitors. Several compounds, for example 42 (AChE IC(50)
      0.03 microM) have been found to reverse the neuromuscular blockade induced by
      vecuronium bromide in vitro and in vivo. Coupled with their high water solubility
      (up to 30-60 mg/mL), these compounds are potentially useful as intravenous
      reversal agents of neuromuscular blocking agents in surgical anaesthesia.

PMID- 12182863
TI  - Structure-activity relationship studies of ethyl 2-[(3-methyl-2,5-dioxo(3
      pyrrolinyl))amino]-4-(trifluoromethyl)pyrimidine-5-carboxylate: an inhibitor of
      AP-1 and NF-kappaB mediated gene expression.
AB  - Several analogues of ethyl 2-[(3-methyl-2,5-dioxo(3-pyrrolinyl))amino]-4
      (trifluoromethyl)pyrimidine-5-carboxylate (1) were synthesized and tested as
      inhibitors of AP-1 and NF-kappaB mediated transcriptional activation in Jurkat T
      cells. From our SAR work, ethyl 2-[(3-methyl-2,5-dioxo(3-pyrrolinyl))-N
      methylamino]-4-(trifluoromethyl)-pyrimidine-5-carboxylate was identified as a
      novel and potent inhibitor.

PMID- 12182864
TI  - Comparison of the prevention of aflatoxin b(1)-induced genotoxicity by quercetin
      and quercetin pentaacetate.
AB  - Earlier work carried out in our laboratory highlighted the mode of action of
      acetoxy 4-methylcoumarins in preventing the genotoxicity of aflatoxin B(1)
      (AFB(1)). We have in this report extended the observations to quercetin
      pentaacetate (QPA), which unlike quercetin (Q) has demonstrated time-dependent
      inhibition of liver microsome catalysed AFB(1) epoxidation as measured by AFB(1)
      binding to DNA. The action of QPA is similar to that of the acetoxy 4
      methylcoumarins in that they are acted upon by microsomal transacetylase leading
      to modulation of catalytic activities of certain enzymes (such as P-450 enzymes,
      NADPH cytochrome C reductase and glutathione S-transferase) possibly by way of
      protein acetylation. In the present work, we have documented the transacetylase
      mediated action of QPA in preventing genotoxicity due to AFB(1).

PMID- 12182865
TI  - Structure-activity relationship of biaryl acylsulfonamide analogues on the human
      EP(3) prostanoid receptor.
AB  - Potent and selective ligands for the human EP3 prostanoid receptor are described.
      Biaryl compounds bearing a tethered ortho substituted acidic moiety were
      identified as potent EP3 antagonists based on the SAR described herein. The
      binding affinity of key compounds on all eight human prostanoid receptors is
      reported.

PMID- 12182866
TI  - 8-Aryl xanthines potent inhibitors of phosphodiesterase 5.
AB  - In clinical studies, several inhibitors of phosphodiesterase 5 (PDE5) have
      demonstrated utility in the treatment of erectile dysfunction. We describe herein
      a series of 8-aryl xanthine derivatives which function as potent PDE5 inhibitors
      with, in many cases, high levels of selectivity versus other PDE isoforms.

PMID- 12182867
TI  - DNA binding ligands with excellent antibiotic potency against drug-resistant gram
      positive bacteria.
AB  - An efficient synthesis of DNA binding molecules consisting of four heterocyclic
      carboxamide units and various substituents at both termini is described. The
      minor-groove binding ligands showed excellent activity against a broad range of
      Gram-positive bacteria; no cross-resistance to known antibacterial drugs was
      observed.

PMID- 12182868
TI  - Parallel synthesis and anti-malarial activity of a sulfonamide library.
AB  - Solution-phase synthesis and evaluation of a library of 31 sulfonamides as
      inhibitors of a chloroquine-resistant strain of Plasmodium falciparum are
      described. The most potent compound displayed an activity 100-fold better than
      chloroquine. Experiments using a fluorescent sulfonamide derivative suggest that
      their site of action inside the parasite is different to that of chloroquine.

PMID- 12182869
TI  - Synthesis and evaluation of 4-hydroxyphenylacetic acid amides and 4
      hydroxycinnamamides as antioxidants.
AB  - 4-Hydroxyphenylacetic acid amides and 4-hydroxycinnamamides were synthesized and
      their antioxidant and neuroprotective activities were evaluated. Among the
      prepared compounds, 8b, and exhibited potent inhibition of lipid peroxidation in
      rat brain homogenates, and marked DPPH radical scavenging activities.
      Furthermore, and exhibited neuroprotective action against the oxidative damage
      induced by the exposure of primary cultured rat cortical cells to H(2)O(2),
      xanthine/xanthine oxidase, or Fe(2+)/ascorbic acid. Based on these results, we
      found that was the most potent antioxidant among the compounds tested.

PMID- 12182870
TI  - The discovery of SB-435495. A potent, orally active inhibitor of lipoprotein
      associated phospholipase A(2) for evaluation in man.
AB  - The introduction of a functionalised amido substituent into a series of 1
      (biphenylmethylacetamido)-pyrimidones has given a series of inhibitors of
      recombinant lipoprotein-associated phospholipase A(2) with sub-nanomolar potency
      and very encouraging developability properties. Diethylaminoethyl derivative 32,
      SB-435495, was selected for progression to man.

PMID- 12182871
TI  - Synthesis and characterization of a new RXR agonist based on the 6-tert-butyl-1,1
      dimethylindanyl structure.
AB  - A new ligand for RXR is described, which is based on a 6-tert-butyl-1,1
      dimethylindanyl skeleton as bioisostere of the hydrophobic retinoid region. The
      Stille cross-coupling reaction allowed the attachment of the polyene side chain
      to the indanyl ring. Docking studies were carried out to explain the RXR binding
      profile of this analogue.

PMID- 12182872
TI  - Synthesis and cytotoxic activity of pyridazino[1',6':1,2]pyrido[3,4-b]indol-5
      inium derivatives as anti-cancer agents.
AB  - Several new pyridazino[1',6':1,2]pyrido[3,4-b]indol-5-inium derivatives were
      synthesised from beta-carboline derivatives and their cytotoxic activity and
      effect on the cell cycle were evaluated against L1210 cancer cells.

PMID- 12182873
TI  - 4-Aminoquinolines as a novel class of NR1/2B subtype selective NMDA receptor
      antagonists.
AB  - Screening of the Roche compound library led to the identification of 4
      aminoquinoline 4 as structurally novel NR1/2B subtype selective NMDA receptor
      antagonist. The SAR which was developed in this series resulted in the discovery
      of highly potent and in vivo active blockers.

PMID- 12182874
TI  - Long-chain aminoalcohol and diamine derivatives induce apoptosis through a
      caspase-3 dependent pathway.
AB  - A number of long chain diamines and aminoalcohols and several of their alkyl,
      acyl and carbamoyl derivatives, have been synthesized and evaluated for their
      apoptotic activities using the Jurkat cell line. Apoptosis was measured by flow
      cytometry and the best results were found for the aminoalcohols displaying either
      a free alcohol or an amine with at least, one free hydrogen atom. The apoptotic
      pathway was mediated by a disruption of the mitochondria transmembrane potential
      and caspase-3 activation, inducing DNA fragmentation at the phase G(1)/S of the
      cell cycle.

PMID- 12182875
TI  - Design, synthesis and biological evaluation of cyclic angiotensin II analogues
      with 3,5 side-chain bridges. Role of C-terminal aromatic residue and ring cluster
      for activity and implications in the drug design of AT1 non-peptide antagonists.
AB  - The novel amide linked angiotensin II (ANG II) cyclic analogues: gamma, epsilon 
      cyclo(3, 5)-[Sar(1)-Glu(3)-Lys(5)-Ile(8)] ANG II (I) and gamma, epsilon -cyclo(3,
      5)-[Sar(1)-Glu(3)-Lys(5)-Phe(8)] ANG II (II) have been designed, synthesized and
      bioassayed in anesthetized rabbits in order to unravel structural ring cluster
      characteristics important for receptor activation. Analogue I with Ile at
      position 8 was an inhibitor of Angiotensin II while analogue II with Phe at
      position 8 was found to be an agonist. Similar results were reported for cyclic
      compounds that have reversed the linking between positions 3 and 5. The overall
      results show that positions 3 and 5 do not govern the biological activity of the
      synthetic analogues. It also appears that the aromatic ring cluster (Tyr-His-Phe)
      in agonist peptides is an essential stereo-electronic feature for Angiotensin II
      to exert its biological activity. A non-peptide mimetic of ANG II, 1-[2'-[(N
      benzyl)tetrazol-5-yl]biphenyl-4-yl]methyl]-2-hydroxymethylbenzimidazole (BZI8)
      has been designed and synthesized. This molecule is more rigid and much less
      active than AT(1) non-peptide mimetic losartan probably because it lacks to mimic
      the orientation of tetrazole and the pharmacophore segments of butyl chain and
      imidazole ring.

PMID- 12182876
TI  - Syntheses of polycationic dendrimers on lipophilic peptide core for complexation
      and transport of oligonucleotides.
AB  - Synthesis of novel polycationic lipophilic peptide core(s) was accomplished and
      these agents successfully transfected human retinal pigment epithelium cells with
      ODN1 upon complexation with the oligonucleotide. The level of transfection was
      indirectly measured by the decreased production of the protein hVEGF (human
      vascular endothelial growth factor) in comparison to the transfection agent
      cytofectin GSV.

PMID- 12182877
TI  - Multisubstrate analogue inhibitors of glucosamine-6-phosphate synthase from
      Candida albicans.
AB  - Compounds 1-6 were designed as multisubstrate inhibitors of glucosamine synthase.
      These compounds are also useful probes for measuring the distances between the
      two active sites in the multidomain protein. Our data suggest that the two
      binding pockets are in close proximity to each other.

PMID- 12182878
TI  - The synthesis of substituted fluorenes as novel non-imidazole histamine h(3)
      inhibitors.
AB  - A novel non-imidazole fluorene oxime 1a has been identified as a histamine H(3)
      inhibitor, and its structure-activity relationship has been evaluated.

PMID- 12182879
TI  - Synthesis and DNA binding properties of saturated distamycin analogues.
AB  - A series of saturated heterocyclic analogues of distamycin were prepared and
      examined. A fluorescent intercalator displacement (FID) assay conducted on p[dA]
      p[dT] DNA to obtain C(50) values and a hairpin deoxyoligonucleotide containing an
      A/T-rich binding site was used to evaluate DNA binding affinity. It is observed
      that saturated heterocycles greatly reduce the DNA binding relative to
      distamycin.

PMID- 12182880
TI  - Oligonucleotides comprised of alternating 2'-deoxy-2'-fluoro-beta-D
      arabinonucleosides and D-2'-deoxyribonucleosides (2'F-ANA/DNA 'altimers') induce
      efficient RNA cleavage mediated by RNase H.
AB  - Chimeric oligonucleotides comprised of alternating residues of 2'-deoxy-2'-fluoro
      D-arabinonucleic acid (2'F-ANA) and DNA were synthesized and evaluated for an
      important antisense property-the ability to elicit ribonuclease H (RNase H)
      degradation of complementary RNA. Experiments used both human RNase HII and
      Escherichia coli RNase HI. Mixed backbone oligomers comprising alternating three
      nucleotide segments of 2'F-ANA and three-nucleotide segments of DNA were the most
      efficient at eliciting RNase H degradation of target RNA, and were significantly
      better than oligonucleotides entirely composed of DNA, suggesting that these
      mixed backbone oligonucleotides may be potent antisense agents.

PMID- 12182881
TI  - Nr-CAM and TAG-1 are expressed in distinct populations of developing
      precerebellar and cerebellar neurons.
AB  - Nr-CAM and TAG-1 interact at the floor-plate during the formation of spinal cord
      commissural projections [Stoeckli, E.T., Landmesser, L.T., Sci. 274 (1995) 1123
      1133; Fitzli, D., Stoeckli, E.T., Kunz, S., Siribour, K., Rader, C., Kunz, B.,
      Kozlov, S.V., Buchstaller, A., Lane, R.P., Suter, D.M., Dreyer, W.J.,
      Sonderegger, P., J. Cell. Biol. 149 (2000) 951-968]. We report here the spatio
      temporal patterns of expression of these two adhesion molecules during the
      development of the lower brainstem (medulla and pons) and cerebellum. Nr-CAM and
      Tag-1 label distinct populations of precerebellar neurons at key steps of their
      development. Nr-CAM expression starts at E11.5-E12 in the floor-plate, that
      constitutes an intermediate target during axon outgrowth and nuclear migration of
      precerebellar neurons. At E13-E14, it is expressed in both floor-plate and
      inferior olivary nuclei (ION) neurons before being strictly restricted to ION
      neurons from E15 onwards. Furthermore Nr-CAM, which is widely expressed in the
      cerebellum during embryonic development, becomes strictly confined to Purkinje
      and Golgi cells in postnatal cerebellum, suggesting a possible role of Nr-CAM for
      the maturation or stabilization of the synaptic contacts, in particular between
      climbing fibers and Purkinje cells. On the other hand, Tag-1 is expressed by
      migrating neurons that will form the lateral reticular and basilar pontine
      nuclei. These results emphasize the possibility that TAG-1/Nr-CAM interactions
      are also involved in the development of the cerebellar system (precerebellar and
      cerebellar neurons). However, the pattern of cerebellar expression of TAG-1-
      early migrating Purkinje cells up to E14 and external granular cells--prevents
      the implication of this adhesion molecule in the organization of extracerebellar
      projections.

PMID- 12182883
TI  - Dopamine D2L receptor knockout mice display deficits in positive and negative
      reinforcing properties of morphine and in avoidance learning.
AB  - The dopamine D2 receptor (D2) is implicated in drug addiction, learning and
      memory. Two isoforms of the D2 receptor, termed D2L (long form) and D2S (short
      form), have been identified. We previously generated mice lacking D2L (D2L-/-),
      but expressing functional D2S. In this study, we investigated the role of D2L in
      the positive and negative reinforcing properties of abused drugs and electrical
      stimuli, using D2L-/- mice as a model system. Mice were trained in three
      associative learning tasks: conditioned place preference to morphine and cocaine,
      conditioned place aversion to naloxone-precipitated morphine withdrawal, and
      active avoidance. D2L-/- mice, like wild type mice, developed a place preference
      to cocaine. In contrast to wild type mice, D2L-/- mice did not develop a place
      preference to morphine, nor did they attain a place aversion to morphine
      withdrawal. D2L-/- mice also failed to acquire avoidance behavior in response to
      electrical stimuli. There were no significant differences between D2L-/- and wild
      type mice in mu-opioid receptor density, morphine-induced locomotor stimulation
      and morphine withdrawal symptoms. These results suggest that D2L may have a
      greater impact than D2S on the rewarding aspects of morphine, and the aversive
      properties of morphine withdrawal and electrical stimulus. These findings also
      suggest that the presence of D2L is critical in the acquisition (learning) and/or
      retention (memory) of context-stimulus associations in certain situations. On the
      other hand, D2L is not essential for the rewarding aspects of cocaine and for the
      development of morphine dependence. Thus, these studies reveal distinct
      functional roles of D2L and/or D2S in drug addiction and avoidance learning,
      which may lead to a better understanding of the neurobiological basis underlying
      these behaviors.

PMID- 12182882
TI  - Repeated cocaine administration alters the electrophysiological properties of
      prefrontal cortical neurons.
AB  - Recently it has become clear that some of the symptoms of addiction such as
      relapse to drug-taking behavior arise, in part, from a dysfunction in cognitive
      and emotional processing. This realization has promoted investigations into the
      physiology and pathophysiology of forebrain circuits that are both innervated by
      dopamine and play an important role in cognitive processing, including the
      prefrontal cortex. In order to study long-term neuroadaptations occurring in the
      prefrontal cortex of the rat as a consequence of psychostimulant administration,
      cocaine was repeatedly administered in either a contingent or a non-contingent
      manner. At least 2 weeks following the last cocaine injection, in vivo
      intracellular recordings were made from neurons located in the deep layers of the
      prefrontal cortex. Repeated cocaine administration abolished the presence of
      membrane bistability normally present in neurons located in the limbic prefrontal
      cortex. These results indicate that repeated exposure to cocaine produces
      enduring changes in the basal activity of neurons in the prefrontal cortex that
      may contribute to previously identify cognitive and emotional dysfunctions in
      cocaine addicts.

PMID- 12182885
TI  - Glycinergic synaptic transmission to bullfrog retinal bipolar cells is input
      specific.
AB  - Glycinergic inhibitory postsynaptic currents (IPSCs) focally elicited at the
      dendrites and axon terminals were recorded from bipolar cells in the bullfrog
      retinal slice, using the whole-cell clamp technique. IPSCs driven by input from
      interplexiform cells at bipolar cell dendrites (ipc-IPSCs) had a much slower
      decay time constant (25.2 +/- 7.8 ms) than IPSCs driven by input from amacrine
      cells at bipolar cell axon terminals (ac-IPSCs) (14.7 +/- 5.5 ms). Furthermore,
      peak-scaled non-stationary noise analysis revealed that the weighted mean single
      channel conductance of the glycine receptors underlying bipolar cell dendritic
      ipc-IPSCs (20.8 +/- 6.6 pS) was significantly larger than that of those
      underlying bipolar cell axon terminal ac-IPSCs (12.9 +/- 2.9 pS). These results
      demonstrate that glycinergic synaptic transmission with different properties at
      bipolar cell dendrites and axon terminals differentially mediates intraretinal
      centrofugal signal transfer from the inner retina to the outer retina provided by
      interplexiform cells and lateral inhibition offered by amacrine cells in the
      inner retina.

PMID- 12182884
TI  - The neuropeptide Y receptors, Y1 and Y2, are transiently and differentially
      expressed in the developing cerebellum.
AB  - Neuropeptide Y (NPY), a peptide widely expressed in the brain, acts through the
      protein G-coupled receptors Y1, Y2 and Y5. In the adult rat, this peptide
      modulates many important functions such as the control of energy balance and
      anxiety. Its involvement in brain development has been less investigated. In the
      present study, we have analysed the expression of Y1 and Y2 in the developing rat
      cerebellum using RNase protection assay. Both receptors were detected in the
      embryo but at very low levels. Their expression then increased, reaching a peak
      at postnatal day 10. At later stages, we observed a down-regulation of both Y1
      and Y2 mRNA levels. This pattern of expression was delayed in hypothyroid rats,
      suggesting that the regulation of NPY receptors was strictly related to
      cerebellar development stages. In situ hybridisation and immunohistochemistry
      analyses revealed specific localisations of the receptors. Y1 was exclusively
      expressed by Purkinje cells while Y2 was found mostly in granule cells of the
      internal granule cell layer. These observations argue in favour of specific roles
      for Y1 and Y2 in the developing cerebellum. In an initial attempt to characterise
      these roles, we have determined the number of apoptotic cells in the developing
      cerebellum of Y2(-/-) mice and analysed the effects of NPY on primary cultures of
      cerebellar granule neurones. Our data showed that the absence of Y2 did not
      increase cell death in the internal granule cell layer of the developing
      cerebellum, and that NPY by itself did not prevent the death of differentiated
      granule cells cultured in serum-free medium. However, we found that co-treatment
      of the cells by NPY and neuromediators such as NMDA or GABA strongly promoted the
      survival of granule neurones. Taken together, these observations suggest an
      involvement of the NPY receptors in cerebellar ontogenesis that remains to be
      demonstrated in vivo.

PMID- 12182886
TI  - Chronic gliosis triggers Alzheimer's disease-like processing of amyloid precursor
      protein.
AB  - Alzheimer's disease is a progressively dementing illness characterized by the
      extracellular accumulation and deposition of beta-amyloid. Early onset
      Alzheimer's disease is linked to mutations in three genes, all of which lead to
      increased beta-amyloid production. Inflammatory changes and gliosis may also play
      a role in the disease process, but the importance of these reactive events
      remains unclear. We recently reported that chronic cortical gliosis in
      heterotopic fetal rat cortical transplants is associated with significant changes
      in the levels of some of the proteins implicated in the pathogenesis of
      Alzheimer's disease. Because rodent beta-amyloid does not form extracellular
      amyloid deposits, we have now extended this model of chronic cortical gliosis to
      transgenic mice expressing the Swedish mutant form of human amyloid precursor
      protein. In addition, apolipoprotein E knockout mice were used to elucidate the
      role of this protein in reactive gliosis. The expression of mutant and murine
      proteins was assayed 6 or 10 months after transplantation using
      immunohistochemical and western blot methods. Heterotopic transplantation of
      fetal cortex onto the midbrain of neonatal mice consistently resulted in reactive
      gliosis, independent of apolipoprotein E status. In contrast, in homotopic cortex
      to-cortex grafts there was little alteration in glial reactivity, a result
      similar to that obtained previously in rats. By 10 months post-transplantation
      the level of presenilin-1 expression was lower in heterotopic grafts than in host
      cortex and there was increased expression of transgenic amyloid precursor
      protein, but only in the gliotic cortex-to-midbrain grafts. Most importantly,
      increased levels of beta-amyloid, and particularly its precursor, C-99, were
      selectively found in these heterotopic transplants. Our results show that chronic
      gliosis is associated with altered processing of the amyloid precursor protein in
      vivo and thus may initiate or exacerbate pathological changes associated with
      Alzheimer's disease.

PMID- 12182887
TI  - Neonatal neuronal overexpression of glycogen synthase kinase-3 beta reduces brain
      size in transgenic mice.
AB  - Glycogen synthase kinase-3beta (GSK-3beta) is important in neurogenesis. Here we
      demonstrate that the kinase influenced post-natal maturation and differentiation
      of neurons in vivo in transgenic mice that overexpress a constitutively active
      GSK-3beta[S9A]. Magnetic resonance imaging revealed a reduced volume of the
      entire brain, concordant with a nearly 20% reduction in wet brain weight. The
      reduced volume was most prominent for the cerebral cortex, without however,
      disturbing the normal cortical layering. The resulting compacted architecture was
      further demonstrated by an increased neuronal density, by reduced size of
      neuronal cell bodies and of the somatodendritic compartment of pyramidal neurons
      in the cortex. No evidence for apoptosis was obtained. The marked overall
      reduction in the level of the microtubule-associated protein 2 in brain and in
      spinal cord, did not affect the ultrastructure of the microtubular cytoskeleton
      in the proximal apical dendrites. The overall reduction in size of the entire CNS
      induced by constitutive active GSK-3beta caused only very subtle changes in the
      psychomotoric ability of adult and ageing GSK-3beta transgenic mice.

PMID- 12182888
TI  - Immunoreactive localisation of P2Y1 receptors within the rat and human nodose
      ganglia and rat brainstem: comparison with [alpha 33P]deoxyadenosine 5'
      triphosphate autoradiography.
AB  - The present study employed standard peroxidase immunohistochemistry to map the
      distribution of P2Y(1) receptors in the rat brainstem and nodose ganglia and
      characterised the binding profile of [alpha(33)P]dATP. Binding of
      [alpha(33)P]dATP was fully displaceable by adenosine 5'-triphosphate (ATP), and
      was found on both human and rat nodose ganglia, and throughout the rat brainstem,
      including the nucleus tractus solitarius and ventrolateral medulla.
      [Alpha(33)P]dATP binding in the human nodose ganglia was significantly displaced
      by both 2-methylthio ATP and alpha,beta-methylene ATP, but not by uridine 5'
      triphosphate, pyridoxalphosphate-6-azophenyl-2',4'-disulfonic acid, 8,8'
      (carbonylbis(imino-4,1-phenylenecarbonylimino-4,1
      phenylenecarbonylimino))bis(1,3,5-naphtalenetrisulfonic) acid (NF279) or N
      ethylcarboxamidoadenosine. [Alpha(33)P]dATP binding in the rat nodose ganglia and
      brainstem was significantly displaced by only 2-methylthio ATP, suggesting that
      [alpha(33)P]dATP is binding to P2Y receptors in the rat. Binding of
      [alpha(33)P]dATP was also significantly displaced by alpha,beta-methylene
      adenosine 5'-diphosphate, suggesting a component of the binding is to endogenous
      ecto-5'-nucleotidase, however, almost all binding could be displaced by a
      combination of receptor agonists (2-methylthio ATP, uridine 5'-triphosphate and
      alpha,beta-methylene ATP), suggesting preferential binding to receptors.
      Immunoreactivity to P2Y(1) receptor (P2Y(1)-IR) exhibited similar distribution
      patterns to [alpha(33)P]dATP binding, with a clear topographic profile.
      Particularly dense P2Y(1)-IR labeling was evident in cells and fibres of the
      dorsal vagal complex. Immunolabeling was also present in the dorsal motor nucleus
      of the vagus and nucleus ambiguus, indicating the possibility of P2Y(1) receptors
      on vagal efferents. Unilateral vagal ligation was also performed to examine the
      transport of P2Y(1) receptor, using both immunohistochemistry and
      [alpha(33)P]dATP autoradiography. Accumulations of both P2Y(1)-IR and
      [alpha(33)P]dATP binding were apparent adjacent to both ligatures, suggesting bi
      directional transport of P2Y(1) receptors along the rat vagus nerve. This current
      study represents the first description of P2Y(1) receptor distribution within the
      rodent brainstem and nodose ganglion and also characterises [alpha(33)P]dATP
      binding to P2Y receptors.

PMID- 12182889
TI  - Early defect in the expression of mouse sperm DNAJ 1, a member of the DNAJ/heat
      shock protein 40 chaperone protein family, in the spinal cord of the wobbler
      mouse, a murine model of motoneuronal degeneration.
AB  - Prevention of protein misfolding is ensured by chaperone proteins, including the
      heat shock proteins (HSP) of the DNAJ/HSP40 family. Detection of abnormal protein
      aggregates in various neurodegenerative diseases has led to the proposal that
      altered chaperone activity contributes to neurodegeneration. Msj-1, a DNAJ/HSP40
      protein located around the spermatozoa acrosome, was recently found to be down
      regulated in the testis of wobbler mutant mice. Wobbler is an unidentified
      recessive mutation which triggers progressive motoneuron degeneration with
      abnormal intracellular protein accumulations, and defective spermatozoa
      maturation. Here, we examined Msj-1 expression in the spinal cord of the mutants
      and their controls. Msj-1 transcripts were amplified by reverse transcription
      polymerase chain reaction from mutant and wild-type spinal cord RNA. Sequencing
      of Msj-1 coding region revealed no change in the mutant. In contrast, decreased
      Msj-1 mRNA levels were observed in five to six-week-old wobbler mice spinal cord,
      when motoneuron degeneration is at its apex, as compared to controls. A similar
      decrease was observed in two-week-old wobbler spinal cord, when the number of
      motoneurons is still unaltered, indicating that the decreased mRNA content is
      intrinsic to the mutant and not simply related to the loss of cells expressing
      Msj-1. Assays of Msj-1 protein levels yielded similar results. Immunofluorescent
      labeling revealed numerous Msj-1-ir motoneurons in five-week-old control spinal
      cord while no signal was observed in age-matched wobbler. Our results show,
      therefore, that Msj-1 expression is down-regulated in both organs affected by the
      wobbler mutation, the CNS and the testis, and that this defect precedes the first
      histological signs of motoneuron degeneration. These results provide the first
      example of an association between transcriptional repression of a chaperone
      protein and a neurodegenerative process.

PMID- 12182891
TI  - The effects of beta-estradiol on SHSY5Y neuroblastoma cells during heavy metal
      induced oxidative stress, neurotoxicity and beta-amyloid secretion.
AB  - The role of estrogen as a neurotrophic/neuroprotective agent in neurodegenerative
      diseases such as Alzheimer's and Parkinson's diseases is increasingly being
      shown. In this study we examine the neuroprotective effects of beta-estradiol on
      SHSY5Y neuroblastoma cells which have been exposed to the heavy metals cobalt and
      mercury. The results show that cobalt and mercury are able to induce oxidative
      stress and cell cytotoxicity and increase the secretion of beta-amyloid 1-40 and
      1-42. These deleterious effects are reversed by the pretreatment of cells with
      beta-estradiol. It is further shown that beta-estradiol exerts its
      neuroprotective action through mechanisms which reduce oxidative stress and
      reduce beta-amyloid secretion. Pre-treatment of the cells with alpha-estradiol
      did not alleviate the toxic effects of the heavy metals. Our results are
      significant as they contribute to a better understanding of the mode of action of
      estrogen with relevance to its use in the treatment of neurodegenerative
      disorders.

PMID- 12182890
TI  - Thyroid hormone distribution in the mouse brain: the role of transthyretin.
AB  - Transthyretin is the major thyroxine-binding protein in the plasma of rodents,
      and the main thyroxine-binding protein in the cerebrospinal fluid of both rodents
      and humans. The choroid plexus synthesizes transthyretin and secretes it to the
      cerebrospinal fluid. Although it was suggested that transthyretin might play an
      important role in mediating thyroxine transfer from the blood into the brain
      across the choroid plexus-cerebrospinal fluid barrier, newer findings question
      this hypothesis. Because thyroid hormone passage across brain barriers is a
      precondition for its action in the CNS, and because brain is an important target
      of thyroid hormone action, we investigated the role of transthyretin in mediating
      thyroid hormone access to and distribution within the brain in a transthyretin
      null mouse model system. In this report we describe the results derived from use
      of film autoradiography, a technique that yields definitive morphological
      results. Film autoradiograms were prepared at 3 and 19 h after intravenous
      injection of either high specific activity [(125)I]thyroxine or
      [(125)I]triiodothyronine. Image analyses were designed to demonstrate regional
      changes in hormone distribution, and to highlight alterations in iodothyronine
      delivery from ventricles to brain parenchyma. We find no qualitative or
      quantitative differences in these parameters between the transthyretin-null and
      the wild-type mouse brain after either [(125)I]thyroxine or
      [(125)I]triiodothyronine administration. The data presented here now provide
      definitive evidence that, under standard laboratory conditions, transthyretin is
      not required for thyroid hormone access to or distribution within the mouse
      brain. This study also provides the first map of iodothyronine distribution in
      the brain of the mouse.

PMID- 12182892
TI  - DCG-IV but not other group-II metabotropic receptor agonists induces microglial
      BDNF mRNA expression in the rat striatum. Correlation with neuronal injury.
AB  - We have previously described a neuroprotective action of (2S,2'R,3'R)-2-(2'3'
      dicarboxycyclopropyl)glycine (DCG-IV), an agonist for group-II metabotropic
      receptors, on dopaminergic nerve terminals against the degeneration induced by 1
      methyl-4-phenylpyridinium (MPP+). This effect was accompanied by an up-regulation
      of brain-derived neurotrophic factor (BDNF) mRNA expression in the rat striatum.
      We have now analyzed the phenotypic nature of the BDNF mRNA-expressing cells in
      response to intrastriatal injection of DCG-IV. Dual in situ hybridization and
      immunohistochemistry revealed that microglial cells but not astrocytes were
      responsible for this induction. Subsequent analysis demonstrated that this effect
      was accompanied by striking loss of striatal glutamic acid decarboxylase (GAD)
      mRNA and massive appearance of internucleosomal DNA fragmentation, a hallmark of
      apoptosis. A dose-response study demonstrated that doses of DCG-IV as low as 5
      nmol was very toxic in terms GAD mRNA and apoptosis. 0.5 nmol of DCG-IV did not
      induce toxicity at all in terms of GAD mRNA and apoptosis. Activation of group-II
      metabotropic receptors in striatum with N-Acetyl-Asp-Glu (NAAG; a mGlu3 agonist)
      and (2R,4R)-4-aminopyrrolidine-2,4-dicarboxylate (a mGlu2 and mGlu3 agonist) did
      not induce neither loss of GAD mRNA nor appearance of apoptosis (doses up to 20
      nmol). In additional experiments, NAAG, in contrast to DCG-IV, failed to protect
      the striatal dopaminergic system against the degeneration induced by MPP+ as
      studied by microdialysis. Finally, we studied the mechanism by which DCG-IV is
      highly toxic. For that, selective antagonists of either metabotropic--(R,S)-alpha
      methyl-4-carboxyphenylglycine and LY 341495--or ionotropic (N-methyl-D-aspartate,
      NMDA)--DL-2-amino-5-phosphonovaleric acid (AP-5) glutamate receptors --were co
      administered with DCG-IV. Only AP-5 highly protected the striatum against the
      degeneration induced by DCG-IV. Since DCG-IV also activates the NMDA receptor at
      concentrations higher than 3 microM, it is conceivable that a intrastriatal
      concentration equal or higher than 3 microM after a single striatal injection of
      5-20 nmol of DCG-IV. Our findings suggest that much caution must be exerted when
      testing the numerous neuroprotective effects ascribed to group-II metabotropic
      receptor activation, in particular when using DCG-IV. We conclude that the
      neuroprotectant capability of a given compound on a specific system does not
      exclude the possibility of inducing toxicity on a different one.

PMID- 12182893
TI  - Grafts of fetal septal cells after cholinergic immunotoxic denervation of the
      hippocampus: a functional dissociation between dorsal and ventral implantation
      sites.
AB  - Three-month-old Long-Evans rats were subjected to intraseptal infusions of 0.8
      microg of 192 IgG-saporin followed, 2 weeks later, by intrahippocampal suspension
      grafts containing fetal cells from the medial septum and the diagonal band of
      Broca. The suspensions were implanted in the dorsal or the ventral hippocampus.
      Sham-operated and lesion-only rats were used as controls. Between 18 and 32 weeks
      after grafting, all rats were tested in a water maze (using protocols placing
      emphasis on reference memory or on working memory) and an eight-arm radial maze.
      The lesion produced extensive cholinergic denervation of the hippocampus, as
      evidenced by reduced acetylcholinesterase-positivity and acetylcholine content.
      Depending upon their implantation site, the grafts restored an
      acetylcholinesterase-positive reinnervation pattern in either the dorsal or the
      ventral hippocampus. Nevertheless, the grafts failed to normalize the
      concentration of acetylcholine in either region. The cholinergic lesion impaired
      working memory performance in both the water maze and the radial maze. To a
      limited degree, reference memory was also altered. Grafts placed in the ventral
      hippocampus had no significant behavioral effect, whereas those placed in the
      dorsal hippocampus normalized working memory performance in the water maze. Our
      data show that infusion of 192 IgG-saporin into the septal region deprived the
      hippocampus of its cholinergic innervation and altered spatial working memory
      more consistently than spatial reference memory. Although the cholinergic nature
      of the graft-induced reinnervation remains to be established more clearly, these
      results further support the idea of a functional dissociation between the dorsal
      and the ventral hippocampus, the former being preferentially involved in spatial
      memory.

PMID- 12182894
TI  - 3 Beta-hydroxysteroid dehydrogenase expression in rat spinal cord.
AB  - In adult male rats, 3beta-hydroxysteroid dehydrogenase/delta5-delta4-isomerase
      (3beta-HSD) expressing cells were identified in the spinal cord from the cervical
      to the sacral segments. An in situ hybridization study, using an oligonucleotide
      common to the four known isoforms of rat 3beta-HSD, revealed its mRNA in gray
      matter. Measurements of optical densities in autoradiograms showed the following
      regional distribution: dorsal horn (layers I-III) > central canal (layer X) > or
      = ventral horn (layers VIII-IX) > ventral funiculus = lateral funiculus. At the
      cellular level, the number of grains was higher on the large motoneurons than on
      small neurons of the dorsal horn, but the grain density per cell was similar.
      Further evidence for the expression of 3beta-HSD in the spinal cord was obtained
      by western blot analysis, which revealed an immunoreactive protein of
      approximately 45 kDa in the dorsal and ventral parts of the spinal cord.
      Castration and adrenalectomy did not influence the expression of 3beta-HSD mRNA
      and protein. Gas chromatography/mass spectrometry measurements showed higher
      levels of pregnenolone and progesterone in the spinal cord than in the plasma.
      After castration and adrenalectomy, their levels remained elevated in the spinal
      cord, suggesting that these neurosteroids may be synthesized locally. The wide
      distribution of 3beta-HSD, and the high levels of pregnenolone and progesterone
      in the spinal cord even after castration and adrenalectomy, strongly suggest a
      potential endogenous production of progesterone and an important signalling
      function of this steroid in the spinal cord.

PMID- 12182896
TI  - Effects of long-term hormone replacement and of tibolone on choline
      acetyltransferase and acetylcholinesterase activities in the brains of
      ovariectomized, cynomologus monkeys.
AB  - We examined long-term effects of low and high doses of tibolone, conjugated
      equine estrogens, and conjugated equine estrogens plus medroxyprogesterone
      acetate on choline acetyltransferase and acetylcholinesterase activities within
      different regions of the brain in cynomologus monkeys. All treatments were
      administered for 2 years. None of the treatments produced significant increases
      in either choline acetyltransferase or acetylcholinesterase in any of eight brain
      regions analyzed. In contrast, treatment with conjugated equine estrogens plus
      medroxyprogesterone acetate, but not conjugated equine estrogens alone, produced
      significant reductions in both choline acetyltransferase and acetylcholinesterase
      in the medial septum/diagonal band of Broca compared with untreated controls.
      Treatment with tibolone also resulted in significant reductions in both choline
      acetyltransferase and acetylcholinesterase in the medial septum/diagonal band of
      Broca, and this effect was dose-related. These findings are the first to report
      the effects of long-term therapies used by postmenopausal women on cholinergic
      measures in the primate brain. The findings are consistent with recent reports in
      rats, and suggest that any positive effects of long-term estrogen or hormone
      replacement therapy on cognitive processes are probably not due to significant
      effects on choline acetyltransferase or acetylcholinesterase activities.

PMID- 12182895
TI  - Overexpression of neuronal Sec1 enhances axonal branching in hippocampal neurons.
AB  - The soluble N-ethylmaleimide-sensitive factor-attached protein receptor (SNARE)
      proteins syntaxin 1 and synaptosomal-associated protein-25 have been implicated
      in axonal outgrowth. Neuronal Sec1 (nSec1), also called murine unc18a (Munc18a),
      is a syntaxin 1-binding protein involved in the regulation of SNARE complex
      formation in synaptic vesicle membrane fusion. Here we analysed whether
      nSec1/Munc18a is involved in neurite formation. nSec1/Munc18a expressed under the
      control of an inducible promoter in differentiated PC12 cells as well as in
      hippocampal neurons appears first in the cell body, and at later times after
      induction along neurites and in growth cones. It is localised to distinct tubular
      and punctated structures. In addition, exogenous nSec1/Munc18a inhibited
      regulated secretion in PC12 cells. Overexpression in PC12 cells of nSec1/Munc18a
      or its homologue Munc18b, reduced the total length of neurites. This effect was
      enhanced with nSec1-T574A, a mutant that lacks a cyclin-dependent kinase 5
      phosphorylation site and displays an increased binding to syntaxin 1. In
      contrast, in hippocampal neurons the total length of all primary neurites and
      branches was increased upon transfection of nSec1/Munc18a. Detailed morphometric
      analysis revealed that this was a consequence of an increased number of axonal
      side branches, while the average lengths in primary neurites and of side branches
      were not affected. From these results we suggest that nSec1/Munc18a is involved
      in the regulation of SNARE complex-dependent membrane fusion events implicated in
      the ramification of axonal processes in neurons.

PMID- 12182897
TI  - Neural activities in the substantia nigra modulated by stimulation of the
      orofacial motor cortex and rhythmical jaw movements in the rat.
AB  - Neurons related to jaw movements in the substantia nigra pars reticulata were
      explored by examining changes in their neural activities in response to
      electrical stimulation of the orofacial sensorimotor cortex and during rhythmical
      jaw movements induced by mechanical stimulation applied to the oral cavity in the
      rat. Out of 80 neurons tested, 59 showed changes in their firing patterns of
      activities in response to the electrical stimulation of the cortex. The
      responding neurons were mainly located in the dorsolateral part of the substantia
      nigra pars reticulata. The substantia nigra pars reticulata neurons showing
      responses were classified into the following five types according to their
      response patterns: (1) an inhibition preceded by an early excitation and followed
      by a late excitation (n = 26), (2) an inhibition preceded by an early excitation
      but not followed by a late excitation (n = 7), (3) an inhibition not preceded by
      an early excitation but followed by a late excitation (n = 2), (4) an inhibition
      without early or late excitations (n = 7) and (5) an excitation without an
      inhibition (n = 17). Out of 18 neurons responding to the cortical stimulation, 11
      (61.1%) increased or decreased their neural activities during rhythmical jaw
      movements. Some of these neurons had a projection to the lateral part of the
      superior colliculus (n = 5) and/or to the parvicellular reticular formation (n =
      2). These results provide first neurophysiological evidence for neurons in the
      dorsolateral part of the substantia nigra pars reticulata with inputs from and
      outputs to the areas related to jaw movements. These neurons may participate in
      the control of jaw movements in the rat.

PMID- 12182898
TI  - Neonatal capsaicin treatment results in prolonged mitochondrial damage and
      delayed cell death of B cells in the rat trigeminal ganglia.
AB  - Capsaicin acts on the vanilloid receptor subtype 1, a noxious heat-gated cation
      channel located on a major subgroup of nociceptive primary afferent neurons.
      Following the systemic capsaicin treatment of neonatal rats, the loss of B-type
      sensory neurons in trigeminal ganglion of adult rats with chemoanalgesia and
      abolition of neurogenic inflammation was investigated. Our quantitative
      morphometric analysis revealed that in the trigeminal ganglion of neonatal rats
      treated with 50 mg/kg s.c. capsaicin, the total number of neurons, morphology of
      B-type cells and cell-size histograms did not differ from that of the controls 1
      or 5 days after treatment. These observations indicate that early cell death does
      not play a significant part in the loss of B-type cells, which in our sample was
      39.4% on the 19th day. However under the electron microscope pronounced selective
      mitochondrial swelling with disorganized cristae was observed in B-type neurons
      at 1-20 weeks after capsaicin treatment. Daily treatment with nerve growth factor
      (NGF, 10 x 100 microg/kg s.c.), started 1 day after capsaicin injection,
      prevented the loss of B-type cells but did not counteract the development of long
      lasting mitochondrial damage. After NGF treatment, partial restitution of
      chemonociception to capsaicin instillation into the eye occurred but capsaicin
      induced inhibition of neurogenic plasma extravasation in the hindpaw evoked by
      topical application of mustard oil remained unaltered. We conclude, that
      capsaicin treatment in neonatal rats, as in the adults, destroys terminal parts
      of the sensory neurons supplied by vanilloid receptors and induces long-lasting
      mitochondrial swelling in the soma. We hypothesize that loss of NGF uptake
      results in delayed cell death of B-type neurons in neonates.

PMID- 12182899
TI  - Ventral striatal anatomy of locomotor activity induced by cocaine, D-amphetamine,
      dopamine and D1/D2 agonists.
AB  - The ventral striatum appears to play a critical role in mediating motoric effects
      (i.e. ambulatory activity and rearing) of psychostimulants such as cocaine. We
      evaluated whether sub-regions of the ventral striatum play differential roles in
      locomotion and rearing induced by various dopaminergic drugs. Injections of D
      amphetamine and dopamine stimulated locomotion and rearing with a similar potency
      at each of the sub-regions: the core, medial shell or medial tubercle. However,
      injections of mixtures of the D(1)- and D(2)-type agonists SKF 38393 and
      quinpirole or cocaine into the medial olfactory tubercle or the medial shell of
      the nucleus accumbens induced marked locomotion and rearing, while these
      injections into the core induced little or no locomotion or rearing. Furthermore,
      cocaine injections into the lateral or posterior tubercle produced marginal
      locomotion and rearing, while cocaine injections into regions just dorsal to
      these tubercle sites, the lateral portion of the shell or the ventral pallidum,
      did not produce any stimulating effect. We conclude that dopaminergic compounds
      induce vigorous locomotion and rearing in both core and shell; the relative roles
      of the core and shell differ depending on chemical compounds. Similar to the
      nucleus accumbens, the olfactory tubercle, particularly the medial portion, also
      mediates these behaviors induced by dopaminergic compounds. The medial ventral
      striatum (i.e. the medial tubercle and medial shell) plays a more important role
      in cocaine-induced locomotion and rearing than the lateral ventral striatum (i.e.
      the core, lateral shell and lateral tubercle). Moreover, the differential effects
      of cocaine between the medial and lateral portions of the shell on locomotion and
      rearing suggest more than two functional units (the core vs. the shell) within
      the accumbens.

PMID- 12182900
TI  - Effects of paired-pulse and repetitive stimulation on neurons in the rat medial
      geniculate body.
AB  - Many behaviorally relevant sounds, including language, are composed of brief,
      rapid, repetitive acoustic features. Recent studies suggest that abnormalities in
      producing and understanding spoken language are correlated with abnormal neural
      responsiveness to such auditory stimuli at higher auditory levels [Tallal et al.,
      Science 271 (1996) 81-84; Wright et al., Nature 387 (1997) 176-178; Nagarajan et
      al., Proc. Natl. Acad. Sci. USA 96 (1999) 6483-6488] and with abnormal anatomical
      features in the auditory thalamus [Galaburda et al., Proc. Natl. Acad. Sci. USA
      91 (1994) 8010-8013]. To begin to understand potential mechanisms for normal and
      abnormal transfer of sensory information to the cortex, we recorded the
      intracellular responses of medial geniculate body thalamocortical neurons in a
      rat brain slice preparation. Inferior colliculus or corticothalamic axons were
      excited by pairs or trains of electrical stimuli. Neurons receiving only
      excitatory collicular input had tufted dendritic morphology and displayed strong
      paired-pulse depression of their large, short-latency excitatory postsynaptic
      potentials. In contrast, geniculate neurons receiving excitatory and inhibitory
      collicular inputs could have stellate or tufted morphology and displayed much
      weaker depression or even paired-pulse facilitation of their smaller, longer
      latency excitatory postsynaptic potentials. Depression was not blocked by
      ionotropic glutamate, GABA(A) or GABA(B) receptor antagonists. Facilitation was
      unaffected by GABA(A) receptor antagonists but was diminished by N-methyl-D
      aspartate (NMDA) receptor blockade. Similar stimulation of the corticothalamic
      input always elicited paired-pulse facilitation. The NMDA-independent
      facilitation of the second cortical excitatory postsynaptic potential lasted
      longer and was more pronounced than that seen for the excitatory collicular
      inputs. Paired-pulse stimulation of isolated collicular inhibitory postsynaptic
      potentials generated little change in the second GABA(A) potential amplitude
      measured from the resting potential, but the GABA(B) amplitude was sensitive to
      the interstimulus interval. Train stimuli applied to collicular or cortical
      inputs generated intra-train responses that were often predicted by their paired
      pulse behavior. Long-lasting responses following train stimulation of the
      collicular inputs were uncommon. In contrast, corticothalamic inputs often
      generated long-lasting depolarizing responses that were dependent on activation
      of a metabotropic glutamate receptor. Our results demonstrate that during
      repetitive afferent firing there are input-specific mechanisms controlling
      synaptic strength and membrane potential over short and long time scales.
      Furthermore, they suggest that there may be two classes of excitatory collicular
      input to medial geniculate neurons and a single class of small-terminal
      corticothalamic inputs, each of which has distinct features.

PMID- 12182901
TI  - Endomorphin-2 inhibits GABAergic inputs to cardiac parasympathetic neurons in the
      nucleus ambiguus.
AB  - The nucleus ambiguus is an area containing cardiac vagal neurons, from which
      originates most of the parasympathetic control regulating heart rate and cardiac
      function. GABAergic pathways to these neurons have recently been described, yet
      modulation of this GABAergic input and its impact upon cardiac vagal neurons is
      unknown. The nucleus ambiguus has been shown to contain mu-opioid receptors and
      endomorphin-1 and endomorphin-2, the endogenous peptide ligands for the mu
      receptor, whilst microinjections of opioids in the ambiguus area evoke
      bradycardia. The present study therefore examined the effects of endomorphin-1,
      endomorphin-2 and DAMGO (a synthetic, mu-selective agonist) on spontaneous
      GABAergic IPSCs in cardiac parasympathetic neurons. Only endomorphin-2 (100
      microM) produced a significant inhibition, of both the frequency (-22.8%) and the
      amplitude (-30.5%) of the spontaneous IPSCs in cardiac vagal neurons. The
      inhibitory effects of endomorphin-2 were blocked by naloxonazine (10 microM), a
      selective mu(1) receptor antagonist. Naloxonazine alone (10 microM) had a
      potentiating effect on the frequency of the GABAergic IPSCs (+161.43%) but not on
      the amplitude, indicating that GABA release to cardiac vagal neurons may be under
      tonic control of opioids acting at the mu(1) receptor. Endomorphin-2 did not
      reduce the responses evoked by exogenous application of GABA. These results
      indicate that endomorphin-2 acts on mu(1) receptors located on precedent neurons
      to decrease GABAergic input to cardiac vagal neurons located in the nucleus
      ambiguus. The subsequent increase in parasympathetic outflow to the heart may be
      one mechanism by which mu-selective opioids act to induce bradycardia.

PMID- 12182902
TI  - Ferritin induction protects cortical astrocytes from heme-mediated oxidative
      injury.
AB  - Hemin is released from hemoglobin after CNS hemorrhage and may contribute to its
      cytotoxic effect. In a prior study, we demonstrated that heme oxygenase-1
      induction protected murine cortical astrocytes from hemoglobin toxicity. Since
      heme metabolism releases iron, this observation suggested that these cells are
      able to effectively sequester and detoxify free iron. In this study, we tested
      the hypotheses that astrocytes increased ferritin synthesis after exposure to
      heme-bound iron, and that this induction protected cells from subsequent exposure
      to toxic concentrations of hemin. Incubation with low micromolar concentrations
      of hemin, hemoglobin, or ferrous sulfate increased ferritin expression, as
      detected on immunoblots stained with a polyclonal antibody that was raised
      against horse spleen ferritin. Time course studies demonstrated an increase in
      ferritin levels within 2 h. Weak and scattered cellular staining was detected by
      immunohistochemistry in control, untreated cultures, while diffuse
      immunoreactivity was observed in cultures exposed to heme-bound iron. An enhanced
      ferritin band was detected on immunoblots from cultures that were treated with
      purified apoferritin, consistent with astrocytic ferritin uptake.
      Immunoreactivity after apoferritin treatment was not altered by concomitant
      treatment with cycloheximide. Pretreatment with apoferritin protected astrocytes
      from hemin toxicity in a concentration-dependent fashion between 1 and 4 mg/ml.
      At the highest concentration, cell death due to a 6-h exposure to 30 microM hemin
      was decreased by about 85%. A protective effect was also produced by induction of
      endogenous ferritin with nontoxic concentrations of ferrous sulfate, hemoglobin,
      or hemin. These results suggest that cortical astrocytes respond to exogenous
      heme-bound or free iron by rapidly increasing ferritin synthesis. The combined
      action of heme oxygenase-1 and ferritin may be a primary astrocytic defense
      against heme-mediated injury.

PMID- 12182903
TI  - Rapid, specific and active site-catalyzed effect of tissue-plasminogen activator
      on hippocampus-dependent learning in mice.
AB  - In the present study we trained tissue-plasminogen activator (tPA)-knockout (tPA 
      /-) and wild-type (tPA +/+) male mice in step-down inhibitory avoidance learning,
      a hippocampus-dependent task. tPA -/- displayed significantly shorter latencies
      to step down at 90 min, one, two and seven days after training indicating the
      learning deficit in these animals (P < 0.05 vs tPA +/+). The locomotor activity,
      the level of anxiety in an elevated-plus maze, as well as the pain threshold did
      not differ between the two strains of mice. The learning disability of tPA -/-
      was overcome by more intense training. The learning deficit was also partially
      restored by limited intrahippocampal delivery of tPA (infused for 2 h before
      training; P < 0.05 vs control), but not by the delivery of urokinase plasminogen
      activator, indicating the acute need for tPA in learning. The beneficial effect
      of tPA was abolished by co-infusion of its inhibitor tPA-STOP, indicating that
      the facilitatory effect of tPA on learning requires a proteolytic step. However,
      tPA activity in the hippocampus was not indispensable for effective memory
      retrieval in tPA-infused tPA -/- mice. Thus, rapid, specific and proteolytic
      action of tPA facilitates hippocampus-dependent learning, but not retrieval of
      previously acquired information.

PMID- 12182904
TI  - Optical monitoring of synaptic summation along the dendrites of CA1 pyramidal
      neurons.
AB  - The primary function of neurons is to integrate synaptic inputs and to transmit
      the results to other cells. Recent studies with somatic whole-cell recordings
      have shown that separate excitatory inputs to hippocampal or cortical pyramidal
      neurons are summated non-linearly. In the present study, we examined how
      postsynaptic potentials (PSPs) are summated along the dendrites employing fast
      optical voltage imaging techniques. Rat hippocampal slices were stained with a
      fluorescent voltage-sensitive dye (JPW1114) and optical signals were monitored
      with a 16 x 16 photodiode array system. Two independent input pathways were
      stimulated individually or in pairs through glass electrodes such that different
      locations of the dendrites received separate synaptic inputs. We found that (1)
      the summation of PSPs was sub-linear along the entirety of dendrites, (2) the
      blockade of GABA(A) receptors suppressed sub-linearity and (3) further blockade
      of GABA(B) receptors suppressed sub-linearity of the summation of separate inputs
      on apical dendrites. Our study demonstrates that pyramidal neurons integrate PSPs
      linearly along the entirety of dendrites; moreover, GABAergic inputs are
      responsible for maintaining sub-linear summation in CA1 pyramidal neurons.

PMID- 12182905
TI  - Insulin, but not proinsulin C-peptide, enhances platelet fibrinogen binding in
      vitro in Type 1 diabetes mellitus patients and healthy subjects.
AB  - INTRODUCTION: Insulin treatment is essential in Type 1 diabetes mellitus (DM).
      However, previous studies have shown complex effects of insulin on platelet
      function. Proinsulin C-peptide has shown beneficial effects in Type 1 DM, but it
      is not known if it can affect platelet activation. We thus investigated how
      insulin, C-peptide, and their combination influence platelets from DM patients
      and healthy subjects. MATERIALS AND METHODS: Hirudinized blood from patients (n =
      10) and healthy subjects (n = 10) was preincubated in the absence or presence of
      insulin (10 and 100 microU/ml), C-peptide (0.3, 1, and 10 nM), or the combination
      (1 nM C-peptide + 100 microU/ml insulin or 10 nM C-peptide + 100 microU/ml
      insulin) and further incubated without or with 10(-6) M ADP. Platelet activation
      was monitored by platelet fibrinogen binding and P-selectin expression using
      whole blood flow cytometry. Data are presented as binding index (BI), which
      integrates the percentage of activated cells and their mean fluorescence
      intensity. RESULTS: Insulin enhanced ADP-induced platelet fibrinogen binding in
      both Type 1 DM patients and healthy subjects. For example, ADP-stimulated
      platelet fibrinogen BI increased from 4.25 +/- 0.74 to 8.63 +/- 2.00 with 10
      microU/ml insulin (P < .05) in Type 1 DM patients. However, insulin did not
      increase platelet P-selectin expression. Proinsulin C-peptide did not influence
      platelet fibrinogen binding or P-selectin expression in either Type 1 DM patients
      or healthy subjects. The combination of C-peptide and insulin had similar effects
      as insulin alone. CONCLUSIONS: Insulin at physiological concentrations enhances
      platelet fibrinogen binding in both Type 1 DM patients and healthy subjects,
      whilst C-peptide does not influence platelet activation.

PMID- 12182906
TI  - Seasonal variations of deep vein thrombosis and its influence on the location of
      the thrombus.
AB  - The role of season as a predisposing factor for the development of deep vein
      thrombosis is controversially discussed. We analysed retrospectively seasonal
      variations in the occurrence of deep vein thrombosis of the leg in 905 patients
      between 1996 and 2000. Additionally, we evaluated the relationship between the
      season and the location of the thrombus. Our study revealed that the frequency of
      deep vein thrombosis of the leg was significantly higher during the winter half
      than during the summer half (p < 0.001). Regarding the seasonal variation of the
      location of the thrombus, distal deep vein thrombosis was more frequent during
      the winter half while proximal deep vein thrombosis was diagnosed more often
      during the summer half of the year. In conclusion, we suggest that the season has
      an influence on the development of deep vein thrombosis in the leg as well as on
      the location of the thrombus.

PMID- 12182907
TI  - The quality of oral anticoagulation before, during and after a period of patient
      self-management.
AB  - The study analyzes the quality of anticoagulation during a 3-year follow-up on
      patients who were treated by an anticoagulation clinic (ACS) for 1 year (Phase
      I), performed weekly self-management of anticoagulation (PSM) after a specific
      training for another year (Phase II) and finally returned to be treated by the
      anticoagulation clinic (ACS) for a third year (Phase III). The mean fraction of
      INR values within therapeutic target range was higher in Phase II (0.69 +/- 0,
      11) compared to Phases I (0.40 +/- 0.20) and III (0.56 +/- 0.18; p < 0.05). Time
      spent in therapeutic target range was higher in Phase II (0.70 +/- 0.10) compared
      to Phases I (0.43 +/- 0.25) and III (0.60 +/- 0.17; p < 0.05). Mean square
      deviation from target value was lower in Phase II (0.39 +/- 0.17) compared to
      Phases I (0.81 +/- 0.44) and III (0.64 +/- 0.39, p = 0.05). Thus, the quality of
      anticoagulation during Phase II (PSM) was significantly better compared to Phases
      I (ACS) and III (ACS) in all endpoints tested. This shows that the quality of
      oral anticoagulation deteriorates again if patient self-management is stopped and
      patients return to conventional treatment. Furthermore, the quality of
      anticoagulation was better in Phase III (post-PSM) compared with Phase I (pre
      PSM) although the type of treatment was identical in both phases (ACS). This
      suggests that the increased patient empowerment and enhanced compliance acquired
      during PSM (Phase II) might have a positive impact on the quality of
      anticoagulation, even when patients return to the conventional treatment (ACS).

PMID- 12182908
TI  - Amino-terminal fragment of urokinase-type plasminogen activator inhibits its
      plasminogen activation.
AB  - The amino terminal fragment (ATF, Ser(1)-Lys(135)) of urokinase-type plasminogen
      activator (uPA) containing an epidermal growth factor-like (EGF) and kringle
      domain is critically involved in some important functions of uPA, such as
      receptor binding and chemotactic activity. In this report, the effect of ATF on
      single-chain uPA (sc-uPA) induced plasminogen activation was investigated. It was
      shown that sc-uPA-induced activation of Glu-plasminogen or Lys-plasminogen was
      significantly inhibited in the presence of ATF. In addition, sc-uPA activation to
      two-chain uPA (tc-uPA) by Lys-plasmin and plasminogen activation to plasmin by tc
      uPA were both found to be inhibited by ATF. The inhibition of these activations
      was significantly attenuated but not diminished when ATF was pretreated with
      immobilized carboxypeptidase B (CPB), indicating that the C-terminal Lys(135) as
      well as internal Lys/Arg residue binding was involved in the mechanism. Kinetic
      analysis showed that sc-uPA activation by Lys-plasmin competitively inhibited by
      ATF and CPB pretreated ATF (CPB-ATF) with an inhibitory constant (K(i)) of 3.8+/
      0.31 and 12.4 +/- 1.8 microM, respectively. In contrast to sc-uPA-induced Glu- or
      Lys-plasminogen activation, sc-uPA-induced mini-plasminogen activation, sc-uPA
      activation by mini-plasmin and mini-plasminogen activation by tc-uPA were not
      affected by ATF. These findings suggested that the inhibitory effects of ATF on
      sc-uPA activation by Lys-plasmin and Glu- or Lys-plasminogen activation by tc-uPA
      were related to the binding of ATF (by its C-terminal Lys(135) and internal
      Lys/Arg residue) with the kringle 1-4 of plasmin and plasminogen, respectively.

PMID- 12182910
TI  - Hyperhomocysteinemia and venous thromboembolism: a risk factor more prevalent in
      the elderly and in idiopathic cases.
AB  - Fasting plasma homocysteine level and the related clinical findings were analysed
      in 240 consecutive patients with venous thromboembolism. Hyperhomocysteinemia,
      defined as a plasma level above 20 micromol/l (corresponding to the percentile
      95th in the controls), was present in 11.2% of the patients. Plasma homocysteine
      level was similar in patients presenting with either deep venous thrombosis,
      pulmonary embolism or both conditions. It was significantly higher in patients
      with primary (unprovoked) VTE than in patients with secondary disease (associated
      with at least one risk factor): 12.3 vs. 9.55 micromol/l (p < 0.005). Mean
      homocysteine was higher in male than in female patients (14.51 vs. 12.9
      micromol/l, p < 0.05) and increased significantly with age. Hyperhomocysteinemia
      was more frequent in patients with relapsing disease (14 of 76, 18.4%) than in
      those presenting with a single episode (13 of 164, 7.9%) (p = 0.034).
      Furthermore, hyperhomocysteinemia was correlated with reduced protein C level (p
      = 0.013). In a multivariate analysis, two factors were significantly associated
      with hyperhomocysteinemia: older age (p < 0.0001) and idiopathic occurrence (p <
      0.02). Since the frequency of homozygous MTHFR thermolabile variant was rather
      similar in patients and controls, testing for C677T mutation was not helpful in
      screening VTE patients. However, the homozygous mutation was significantly more
      prevalent among hyperhomocysteinemia patients, confirming its role in the genesis
      of hyperhomocysteinemia. According to its prevalence, to the putative role in
      venous and arterial disease and the availability of an effective and low-cost
      corrective therapy, hyperhomocysteinemia deserves interest, especially in the
      elderly and in the patients with idiopathic VTE disease.

PMID- 12182909
TI  - Absence of paradoxical thrombin activation by fibrin-specific thrombolytics in
      acute myocardial infarction: comparison of single-bolus tenecteplase and front
      loaded alteplase.
AB  - OBJECTIVES: Thrombolytic therapy in patients with acute myocardial infarction is
      hampered by bleeding complications and procoagulant effects favoring early
      reocclusion. TNK-tPA was shown in vitro to have considerable fibrin specificity.
      We investigated the effects of tenecteplase (TNK-tPA) and alteplase (rt-PA) on
      the haemostasis and fibrinolytic system. METHODS AND RESULTS: We enrolled 30
      patients with AMI into the study. Twenty patients received front-loaded rt-PA up
      to 100 mg; 10 patients were given TNK-tPA in a single bolus up to 50 mg. All
      patients received aspirin and intravenous heparin. During the first 2 days, the
      following parameters were repetitively determined: thrombin-antithrombin III
      complexes (TAT), antithrombin III (ATIII), prothrombin fragment F 1 + 2 (F 1 +
      2), kallikrein-like activity (KK), activated factor XII (FXIIa), plasmin alpha 2
      antiplasmin complexes (PAP), fibrinogen, D-dimers (DD), tissue-type plasminogen
      activator (t-PA). A total of 75 healthy persons served as control group. TAT
      increased significantly after rt-PA but not after TNK-tPA (3 h: 38.1 +/- 29.4
      versus 10.5 +/- 4.2 microg/l; p < 0.01), indicating paradoxical thrombin
      activation. F 1 + 2 increased transiently after rt-PA but not after TNK-tPA.
      Fibrinogen was significantly lower after rt-PA versus TNK-tPA (3 h: 163 +/- 27
      versus 380 +/- 54 mg/dl; p < 0.05). KK activities in the rt-PA group were
      significantly (p < 0.01) increased over 48 h versus TNK-tPA. PAP and D-dimers
      were lower over the time course of 48 h in the tenecteplase group versus rt-PA.
      CONCLUSIONS: This study indicates that tenecteplase has higher fibrin specificity
      not only in vitro but also in vivo versus alteplase. TNK-tPA consecutively has no
      paradoxical systemic procoagulant effect due to the lower extent of activation of
      the kallikrein-factor XII system than alteplase.

PMID- 12182911
TI  - Cancer-related thrombotic microangiopathy secondary to Von Willebrand factor
      cleaving protease deficiency.
AB  - Cancer-related thrombotic microangiopathy (TM) is a serious complication with a
      short-term life-threatening prognosis. This complication shares certain
      similarities with thrombotic thrombocytopenic purpura and hemolytic uremic
      syndrome, both characterized by circulating platelet aggregates containing
      ultralarge multimers of Von Willebrand factor (VWF). We report a case of cancer
      related thrombotic microangiopathy secondary to disseminated metastatic cancer
      with undetectable serum Von Willebrand factor-cleaving protease activity and no
      evidence of serum inhibitory antibody. A concomitant decrease of Ca 19-9 level
      and hemolysis was observed during chemotherapy, in parallel with normalization of
      Von Willebrand factor-cleaving protease activity. The role of ultralarge
      multimers of Von Willebrand factor in platelet aggregation in the context of
      metastatic disease is discussed with respect to our findings in this case of
      cancer-related thrombotic microangiopathy.

PMID- 12182913
TI  - Platelet sialic acid as a potential pathogenic factor in coronary heart disease.
AB  - It was previously reported that, compared to healthy individuals, patients with
      coronary heart disease (CHD) exhibit a higher proportion of platelets with lower
      densities and higher propensity to aggregate. Reasons for this increased tendency
      to aggregate were unknown but appeared to be independent of the patient's age,
      gender, or smoking habits. Sialic acid (N-acetyl-neuraminic acid), a negatively
      charged sugar and constituent of many glycoproteins and gangliosides, is known to
      confer the bulk of negative charges to mammalian cell surfaces. These negatively
      charged surfaces can help cells of the bloodstream to maintain a relative
      distance from each other due to repulsion of the same (negative) charges. In this
      study, we examined whether differences in platelet sialic acid are a potential
      pathogenic factor in patients with coronary heart disease. Upon isolating
      platelets, we found a significantly higher (p < 0.05) proportion of low density
      platelets in patients compared to healthy controls, which is in accordance with
      previously published data. We found significantly less (p < 0.05) sialic acid in
      platelets from patients compared to the control. Most of the platelet total
      sialic acid was susceptible to cleavage by neuraminidase, demonstrating sialic
      acid to be preferably localized at the outer platelet surface. We conclude that
      the lower sialic acid content found in platelets from CHD patients could
      represent a contributing factor for the observed higher aggregability of
      platelets from these patients. Due to the lower sialic acid content and resulting
      lower negative surface charge, less repulsion between the platelets could
      facilitate aggregation.

PMID- 12182912
TI  - Heme oxygenase-1 gene promoter polymorphism is associated with abdominal aortic
      aneurysm.
AB  - OBJECTIVE: Vascular inflammation is a hallmark in the development of abdominal
      aortic aneurysms (AAA). Heme oxygenase-1 (HO-1) is a novel vascular anti
      inflammatory factor. A (GT)(n) dinucleotide repeat in the HO-1 gene promoter
      shows a length polymorphism that modulates the level of gene transcription. Short
      (< 25 GT) repeats are associated with an increased HO-1 upregulation in response
      to inflammatory stimuli than are longer repeats. We hypothesised that patients
      with AAA had less frequently short repeats in the HO-1 gene promoter compared to
      patients with coronary (CAD) or peripheral artery disease (PAD), or healthy
      controls. METHODS: 70 consecutive patients with atherosclerotic AAA, each 70 age-
      and sex-matched patients with CAD and PAD as well as 61 unmatched healthy
      atherosclerosis-free controls for a total of 271 individuals were studied. The
      frequency of carriers of short repeats in the HO-1 gene promoter was determined
      and compared between the groups. RESULTS: In the AAA group, 29 patients (41%)
      were carriers of short (GT)(n) repeats compared to 47 patients (67%) in the CAD
      group, 44 patients (63%) in the PAD group and 35 healthy controls (59%). Patients
      with AAA were less frequently carriers of short repeats compared to age- and sex
      matched patients with CAD (OR = 0.38, p = 0.006) and PAD (OR = 0.35, p = 0.01).
      Healthy controls exhibited short alleles more frequently than patients with AAA
      (p = 0.04), but comparable to CAD (p = 0.3) and PAD patients (p = 0.7).
      CONCLUSION: Patients with AAA were less frequently carriers of short (< 25 GT)
      repeats in the HO-1 gene promoter than patients with atherosclerosis or healthy
      subjects. This suggests that short alleles, and thus, facilitated upregulation of
      HO-1, may be a protective anti-inflammatory factor against the development of
      AAA.

PMID- 12182914
TI  - Resveratrol and vitamin C as antioxidants in blood platelets.
AB  - We investigated the effects of two different compounds with potential
      antioxidative action (found in many fruits, which can be used in therapy of
      cardiovascular disorders): trans-resveratrol (3,4',5-trihydroxystilbene) and
      vitamin C on oxidative stress in blood platelets. Oxidative stress in blood
      platelets was estimated by the measurement of: (1) the generation of superoxide
      radicals (O(2)(-*)) (reduction of cytochrome c) and other reactive oxygen species
      -ROS: H(2)O(2), singlet oxygen and organic radicals (chemiluminescence), (2) the
      production of thiobarbituric acid reactive substances (TBARS) and the level of
      conjugate dienes as markers of lipid peroxidation. We have shown that vitamin C
      at the concentrations of 750-3000 microM, but not at the concentration of 100
      microM (prooxidative action) significantly inhibited peroxidation of lipids
      (measured by TBARS and conjugate dienes) and the production of ROS in blood
      platelets. After the incubation of blood platelets for 30 min at 37 degrees C
      with vitamin C at the concentration of 3000 microM, inhibition of ROS generation
      (above 90%) was achieved. The inhibition of ROS production caused by resveratrol
      at physiological plasma concentrations 0.05-2 microM was lower than by vitamin C.
      At the highest concentration of vitamin C used (3000 microM), the inhibition of
      O(2)(-*) generation was about 40%. Moreover, we did not observe any synergistic
      action of resveratrol and vitamin C at antioxidative dose (3000 microM) on the
      inhibition of lipid peroxidation and the production of O(2)(-*) or ROS in blood
      platelets. Resveratrol as an antioxidant reduced oxidative stress in blood
      platelets caused by vitamin C at prooxidative dose (100 microM).

PMID- 12182915
TI  - Development of a non-human primate sub-clinical model of heparin-induced
      thrombocytopenia: platelet responses to human anti-heparin-platelet factor 4
      antibodies.
AB  - The purpose of this study was to characterize the responses of human and non
      human primate (Macaca mulatta) platelets to anti-heparin-platelet factor 4
      (AHPF4) antibodies. Due to the variations observed in the functionality and
      immunoglobulin isotypes in patients with heparin-induced thrombocytopenia (HIT),
      we used highly characterized human AHPF4 antibodies to study platelet activation
      responses. Using ELISA and 14C-serotonin release assay (SRA) systems, three
      patients' plasmapheresis fluid with similar responses to these assays were
      pooled. This pool was then used to study the platelet activation responses of
      human and primate platelets in the HIT platelet aggregation assay, a flow
      cytometry assay, and a variation of the aggregation assay in which glycoprotein
      IIb/IIIa inhibitors were supplemented. In the plasmapheresis fluid from three
      patients, the most significant AHPF4 immunoglobulin isotype present (based on
      optical density readings) was IgG, with less IgM (p < 0.001) and IgA (p < 0.001).
      The SRA yielded equivalent platelet activation results in all three patients.
      Using this pool in the platelet aggregation assay, without any heparin present,
      there was less percent aggregation (p < 0.001) with human platelets (11.8 +/-
      2.35, n = 5) compared to the primate platelets (54.3 +/- 10.2, n = 9). In
      presence of 0.4 U/ml heparin, both platelet types had similar percent
      aggregations (p > 0.05). Three glycoprotein IIb/IIIa receptor inhibitors were
      used to evaluate the similarities in platelet activation. Eptifibatide was found
      to be a strong inhibitor of both species' platelet types at concentrations
      greater than 0.01 microg/ml. This was not the case with tirofiban which inhibited
      both human and monkey platelets at concentrations greater than 0.025 microg/ml.
      Abciximab inhibited aggregation at concentrations greater than 6.25 microg/ml.
      These data indicate that phylogenetic similarities in platelets of humans and
      primates may be used to further characterize the pathophysiology of HIT syndrome.

PMID- 12182916
TI  - Separation of active and inactive forms of human antithrombin by heparin affinity
      chromatography.
AB  - During the manufacturing of an antithrombin preparation, it is necessary to
      define all steps that may damage or alter the target molecule, and thus decrease
      the biological activity of the inhibitor in blood coagulation. Pasteurization,
      commonly used procedure for viral inactivation of plasma derived antithrombin
      concentrates, was shown to partially alter the conformation of the active native
      antithrombin to an inactive latent form. To study intensively the different forms
      of inactive antithrombin that are formed upon heat treatment, human alpha
      antithrombin, human beta-antithrombin and an equimolar mixture of the two
      isoforms were incubated at 60 degrees C for 15 h in the presence of citrate as
      stabilizing agent. Using two subsequent heparin affinity chromatography steps,
      three different inactive fractions were separated. By comparison of the heparin
      binding capacities, isoelectric points and unfolding characteristics of these
      inactive forms, the alpha-latent and beta-latent antithrombin isoforms could be
      identified. It was also shown that additional inactive forms such as proteinase
      cleaved and/or oxidized forms of antithrombin are formed during the heat
      treatment process. In four commercially available antithrombin preparations, all
      produced by pasteurization, the amount of inactive protein varied between 0.5%
      and 9.5%.

PMID- 12182917
TI  - Enhanced endogenous thrombolysis induced by a specific factor Xa inhibitor, DX
      9065a, evaluated in a rat arterial thrombolysis model in vivo.
AB  - We have previously established an animal model to investigate mechanisms of
      arterial thrombolysis in vivo and have demonstrated that endogenous thrombolysis,
      mediated by thrombin-activatable fibrinolysis inhibitor, is enhanced by
      administration of specific thrombin inhibitors. The aim of the present study was
      to evaluate the effects of a synthetic and specific factor Xa inhibitor, DX
      9065a, on endogenous fibrinolysis. Mural thrombi were formed in rat mesenteric
      arterioles by helium-neon laser irradiation in the presence of Evans blue.
      Thrombolysis was continuously monitored by video microscopy and was quantified
      using image analysis software. Oral and intravenous administration of DX-9065a
      enhanced endogenous thrombolysis in vivo. The mechanisms require additional
      investigation using other experimental systems, but nevertheless, the present
      results extended our previous findings and further suggested that the enhanced
      fibrinolysis might be due to depressed activity thrombin-activatable fibrinolysis
      inhibitor. The synthetic factor Xa inhibitor could provide the basis for a useful
      thrombolytic agent.

PMID- 12182918
TI  - Assessment of platelet activation after exercise using a standardized whole blood
      flow cytometry assay.

PMID- 12182920
TI  - Mood disorders in late life: a patient's perspective.

PMID- 12182921
TI  - Discovery and development of antidepressants: a perspective from a pharmaceutical
      discovery company.

PMID- 12182922
TI  - Diagnosis of late life depression: the view from primary care.
AB  - In the typical primary care practice, in which patients with a wide range of
      diseases and symptoms present with numerous needs, concerns, and requests, a
      chronic disease that lacks quantitative, biologically based diagnostic testing,
      such as depression, can present a daunting diagnostic challenge to even the best
      and most dedicated primary care physician. Depression does not compete well for
      patient and physician time and energy with other medical problems and medical co
      morbidity in patients who seek care from their primary care physician. Primary
      care patients may be more comfortable with and accepting of depression being
      framed as a "normal" chronic disease rather than a psychiatric "brain" disease
      subject to cultural and generational stigmas, nihilism, and prejudice. Insurance
      parity in mental health care would make depression and other mental illness more
      legitimate in the eyes of patients, family members, employers, and physicians. Of
      particular value would be new and creative approaches to collaborative care,
      including telephone monitoring, nurse clinician outreach, and improved
      availability of psychiatric consultation in primary care, because elderly
      depressed patients often see the care of their depression as part of the
      integrated care of multiple chronic medical diseases, rather than a separate
      psychiatric problem to be referred for specialty care.

PMID- 12182923
TI  - Assessment of late life depression.
AB  - This article focuses on diagnostic and nosologic challenges intrinsic to
      geriatric depression, including characteristics interfering with symptom and
      syndrome ascertainment, the impact of medical and cognitive disorders, the
      usefulness of screening instruments, and barriers imposed by treatment settings.
      The article also identifies gaps in existing knowledge and outlines a research
      agenda. Nosologic characterization of depressives syndromes contributed by
      specific medical disorders may lead to effective strategies for prevention and
      treatment of depression. Studies need to examine whether treatment of depression
      can improve the outcome of medical illnesses requiring active patient involvement
      in treatment. Considering disability a distinct aspect of health status may add
      an important dimension to the assessment of depression and result in
      complementary interventions aimed at depression and disability concurrently. The
      provisional criteria for depression of Alzheimer's disease, if validated, may
      facilitate treatment research. Studies need to characterize cognitive
      dysfunctions associated with later development of dementia or poor treatment
      response in patients with depression. Care managers working together with primary
      care physicians can improve the recognition and treatment of depressed elderly
      patients by obtaining the training in using validated instruments and treatment
      algorithms.

PMID- 12182924
TI  - Psychosocial risk factors for depressive disorders in late life.
AB  - This article summarizes research findings on psychosocial risk factors for late
      life depressive disorders. The article draws heavily on longitudinal cohort
      studies of well-defined, population-based samples with diagnostic measures that
      assess the risk of incident or new-onset depressive episodes. These studies have
      identified a number of significant psychosocial risk factors for late life
      depressive disorders, including life events and ongoing difficulties; death of a
      spouse or other loved one; medical illness and injuries; disability and
      functional decline; and lack of social contact. Additional evidence suggests that
      the impact of these psychosocial risk factors on depression can be enhanced or
      buffered by personal or environmental factors. Although many of these
      psychosocial risk factors are more prevalent among older than younger adults, it
      is not clear that their impact on the risk of depression differs by age.
      Methodological challenges to advancing research on psychosocial risk factors for
      late life depression are reviewed, including problems related to study designs,
      sample selection, and measurement.

PMID- 12182925
TI  - Biological risk factors in late life depression.
AB  - A number of biological risk factors have been tentatively identified for unipolar
      and bipolar disorder in the elderly. The list includes genetic factors as well as
      medical illness in general and vascular disease in particular. Most of these risk
      factors have been identified on the basis of cross sectional studies rather than
      longitudinal studies. There is a need for long term epidemiologic and prevention
      studies (in the case of modifiable risk factors). The modifiable risk factors
      include medical illness in general and vascular disease in particular. An example
      is the use of antidepressants following stroke to prevent the onset of
      depression. Of particular interest is the role of vascular risk factors and MRI
      changes suggesting subtle cerebrovascular disease in the development of
      depression and bipolar disorder in late life. The changes have been established
      using both clinical samples and in the case of depression in cross sectional
      epidemiologic samples. The location of these cerebrovascular changes has
      contributed to our understanding of the regions of the brain implicated in the
      pathophysiology of depression. Further longitudinal and preventive studies are
      needed to conclusively demonstrate these as biological risk factors.

PMID- 12182926
TI  - Risk factors for suicide in later life.
AB  - Suicide rates are higher in later life than in any other age group. The design of
      effective suicide prevention strategies hinges on the identification of specific,
      quantifiable risk factors. Methodological challenges include the lack of
      systematically applied terminology in suicide and risk factor research, the low
      base rate of suicide, and its complex, multidetermined nature. Although variables
      in mental, physical, and social domains have been correlated with completed
      suicide in older adults, controlled studies are necessary to test hypothesized
      risk factors. Prospective cohort and retrospective case control studies indicate
      that affective disorder is a powerful independent risk factor for suicide in
      elders. Other mental illnesses play less of a role. Physical illness and
      functional impairment increase risk, but their influence appears to be mediated
      by depression. Social ties and their disruption are significantly and
      independently associated with risk for suicide in later life, relationships
      between which may be moderated by a rigid, anxious, and obsessional personality
      style. Affective illness is a highly potent risk factor for suicide in later life
      with clear implications for the design of prevention strategies. Additional
      research is needed to define more precisely the interactions between emotional,
      physical, and social factors that determine risk for suicide in the older adult.

PMID- 12182927
TI  - Depression as a risk factor for non-suicide mortality in the elderly.
AB  - Depression can be a consequence of medical illness and disability, yet recent
      literature suggests it may also influence morbidity and mortality through a
      variety of behavioral and biological mediators. Relatively little is known about
      the complex temporal relations among behavior, affect, motivation, and
      pathophysiology to account for the association between depression and mortality.
      We performed a systematic review of the recent literature (1997-2001) examining
      the evidence linking depression to non-suicide mortality, describe possible
      mediators of the depression mortality effect, and identify important next steps
      in this area of research, including: a) the development of well-specified a
      priory mediator models that articulate how depression leads to mortality; b) the
      conduct of longitudinal studies in which depression and behavioral and
      pathophyisological mediators are assessed simultaneously; c) treatment studies
      for depression that include assessments of associated changes in health-related
      quality of life, medical morbidity, and mortality; and d) treatment studies for
      behavioral risk factors and medical conditions that include assessment of
      depressive symptoms.

PMID- 12182928
TI  - Medical comorbidity and late life depression: what is known and what are the
      unmet needs?
AB  - Depression is an important problem in older patients with multiple medical
      problems, where the under-recognition and undertreatment of depression is
      especially common. A large number of studies assessing the relationship between
      depression and medical burden have focused on patients with cardiac disease, and
      recent research has focused on the role of depression as an independent risk
      factor for cardiac disease, mortality, and functional status in elderly patients.
      In particular, among coronary bypass surgery patients, depressive symptoms were
      found to occur most commonly in those with the highest comorbidity. In the
      treatment of depression in older adults, both pharmacologic and psychosocial
      interventions have shown promise, but such treatments need to be tested to
      determine whether mortality and functional status are affected. From a
      methodological perspective, new studies will need to control for comorbid
      disease, as many previous studies suggesting depression as a risk factor for
      mortality in cardiovascular patients have not consistently done so.

PMID- 12182929
TI  - Comorbid psychiatric disorders in late life depression.
AB  - In late life depression, common comorbid psychiatric disorders are alcohol use,
      anxiety, and personality disorders. Elderly depressed patients are three to four
      times more likely to have an alcohol use disorder compared with nondepressed
      elderly subjects, with a prevalence of 15%-30% in patients with late life major
      depression. While the presence of a comorbid alcohol use disorder may worsen the
      prognosis for geriatric depression, limited data suggest that successful
      treatment of depression combined with reducing alcohol use leads to the best
      possible outcomes. Most studies show that the overall prevalence of anxiety
      disorders, particularly panic disorder and obsessive-compulsive disorder, is low
      in geriatric depression, but generalized anxiety disorder may not be uncommon. It
      remains unclear if the presence of a comorbid anxiety disorder impacts on the
      treatment and prognosis of late life major depression. Personality disorders
      occur in 10%-30% of patients with late life major depression or dysthymic
      disorder, particularly in patients with early onset depressive illness. Cluster C
      disorders, including the avoidant, dependent, and obsessive-compulsive subtypes
      predominate, while Cluster B diagnoses, including borderline, narcissistic,
      histrionic and antisocial, are rare. Overall, the research database on comorbid
      psychiatric disorders in major and nonmajor late life depression is relatively
      sparse. Since comorbid psychiatric disorders affect clinical course and
      prognosis, and may worsen long-term disability in late life depression,
      considerably more research in this field is needed.

PMID- 12182931
TI  - Post stroke depression: epidemiology, pathophysiology, and biological treatment.
AB  - Depression is a common occurrence after stroke and is associated with excess
      disability, cognitive impairment, and mortality. The authors undertook a
      systematic review of the English language literature to review several aspects of
      this illness, including the prevalence of this disorder, the debate on its
      etiology, and the current understanding of the biological treatment of poststroke
      depression. Methodological problems encountered in the study of poststroke
      depression are highlighted throughout the manuscript. The authors conclude that
      the available evidence supports poststroke depression as being multifactorial in
      origin and consistent with the biopsychosocial model of mental illness.

PMID- 12182930
TI  - Depression in Alzheimer's disease: overview and treatment.
AB  - Psychiatric disturbances affect as many as 90% of patients with Alzheimer's
      disease (AD) and are a major focus of treatment. Depression is one of the most
      frequent psychiatric complications of AD, affecting as many as 50% of patients.
      In this context, depression is a significant public health problem that has a
      series of serious adverse consequences for patients and their caregivers. There
      has been little research into the course or treatment of depression associated
      with AD. This is in part due to the absence of validated operational criteria for
      defining depression in AD. Recently, the National Institute of Mental Health
      (NIMH) convened an expert consensus panel to develop draft criteria for
      depression of Alzheimer's disease (NIMH-dAD) and to establish research priorities
      in this area. This article provides an overview of recent knowledge with regard
      to depression in AD with a special emphasis on its treatment. We conclude with
      recommendations for further research in this area.

PMID- 12182932
TI  - Drug and ECT treatment of depression in the elderly, 1996-2001: a literature
      review.
AB  - A computer-based literature search of all antidepressant and electroconvulsive
      therapy (ECT) treatment studies published between 1995 and September 2001 was
      conducted. In addition, a review of published chapters, review articles, and
      metaanalyses was also conducted. Articles were categorized into those reporting
      comparative studies, those in which the therapeutic agent was not compared with
      another, articles about ECT, and review articles. These recent publications
      support the conclusions from prior reviews that antidepressants and ECT are
      effective and safe treatments for depressed elderly patients. Differences in
      efficacy and side effects appear to be slight among the various types of
      antidepressants. Research studies of depressed elderly increased markedly since
      1995 compared with all previous years although more studies are still necessary.

PMID- 12182933
TI  - Diagnosis and treatment of older adults with depression in primary care.
AB  - This article provides an overview of current challenges in the diagnosis and
      treatment of depressed older adults in primary care and considers suggestions for
      clinicians, researchers, and policy makers to improve care for this population.
      Despite the enormous toll of depression on individuals and society and the
      availability of effective treatments, depressed older adults remain largely
      untreated or undertreated. They rarely see mental health professionals, but have
      relatively frequent contact with primary care providers. In primary care, the
      chronic and recurrent nature of depression and a number of patient, provider, and
      policy-related barriers interfere with effective depression treatment. Recent
      research suggests that improving care for individuals with late life depression
      will require education and engagement of older adults and their primary care
      providers as active partners in caring for depression. It will also require
      additional human resources and systematic models of care dedicated to proactively
      managing depression as a chronic illness. Finally, it will require training of
      mental health professionals to effectively collaborate with their colleagues in
      primary care in treating depressed older adults. Further improvement in
      depression care would likely result from the implementation of true parity for
      mental health treatments for older adults.

PMID- 12182934
TI  - Psychotherapy and combined psychotherapy/pharmacotherapy for late life
      depression.
AB  - Over the past 20 years, numerous studies have investigated the efficacy of
      psychotherapy for treating late life depression and, to a lesser degree, the
      efficacy of psychotherapy combined with antidepressant medication. Of the
      intervention studies, cognitive-behavioral therapy and interpersonal
      psychotherapy combined with antidepressant medication have the largest base of
      evidence in support of their efficacy for late life depression. To a lesser
      degree, there is support for stand-alone interpersonal psychotherapy, brief
      dynamic therapy, and life review treatments. The purpose of this review is to
      present data on the acute and long-term effects of cognitive-behavioral therapy,
      interpersonal psychotherapy, brief dynamic therapy, and combined antidepressant
      medication and psychotherapy to discuss the generalizability of these
      interventions, and to discuss future research directions and the need for
      increased opportunities for this area of research.

PMID- 12182936
TI  - A ubiquitin-like peptide from the mushroom Pleurotus sajor-caju exhibits
      relatively potent translation-inhibitory and ribonuclease activities.
AB  - The fruiting bodies of the edible mushroom Pleurotus sajor-caju were extracted
      with an aqueous buffer and then subjected to affinity chromatography on Affi-gel
      Blue gel, ion exchange chromatography on DEAE-cellulose and gel filtration on
      Superdex 75. From the fraction of the extract adsorbed on Affi-gel Blue gel and
      unadsorbed on DEAE-cellulose, a 9.5 kDa peptide with an N-terminal sequence
      similar to ubiquitin was isolated with a yield of 0.25 mg/kg mushroom. The
      peptide inhibited cell-free translation with an IC(50) of 30 nM. It exhibited a
      ribonuclease activity of 450 U/mg toward yeast transfer RNA. The activities were
      substantially more potent than those of previously isolated mushroom ubiquitin
      like protein and peptide.

PMID- 12182937
TI  - Neuropeptide F and its expression in the yellow fever mosquito, Aedes aegypti.
AB  - A neuropeptide F (NPF) was isolated from an extract of adult Aedes aegypti
      mosquitoes based on its immunoreactivity in a radioimmunoassay for Drosophila
      NPF. After sequencing the peptide, cDNAs encoding the NPF were identified from
      head and midgut. These cDNAs encode a prepropeptide containing a 36 amino acid
      peptide with an amidated carboxyl terminus, and its sequence shows it to be a
      member of the neuropeptide F/Y superfamily. Immunocytochemistry and Northern
      blots confirmed that both the brain and midgut of females are likely sources of
      NPF, found at its highest hemolymph titer before and 24 h after a blood meal.

PMID- 12182938
TI  - A novel GGNG-related neuropeptide from the polychaete Perinereis vancaurica.
AB  - The GGNG peptides are myoactive peptides so far identified from earthworms and
      leeches, which are the earthworm excitatory peptides (EEP) and the leech
      excitatory peptide (LEP), respectively. A novel GGNG peptide was isolated and
      structurally determined from a marine polychaete, Perinereis vancaurica, using a
      combination of immunological assay and high performance liquid chromatography
      (HPLC). The peptide was a pentadecapeptide whose amino acid sequence was similar
      to that of EEP and LEP, and showed myoactivity on isolated esophagus of P.
      vancaurica with a threshold concentration of 10(-10)M. The peptide was designated
      as polychaete excitatory peptide (PEP). Amidation of the alpha-carboxyl group of
      C-terminal residue occurred in PEP. This is the case for LEP, but not for EEP.
      The cDNA cloning revealed that the structure of the PEP precursor is more similar
      to the EEP precursor than to the LEP precursor. Immunohistochemical staining
      showed the presence of PEP in several neurons of central nervous system (CNS) as
      somata and neuropile structure, epithelial cells of the pharynx and epidermal
      cells throughout the body wall. Altogether these results support the
      physiological significance of PEP in regulation of the CNS neural activity and
      the peripheral myoactivity.

PMID- 12182939
TI  - Histatin 5 and derivatives. Their localization and effects on the ultra
      structural level.
AB  - Histatins, a family of cationic peptides present in saliva, are active against
      the opportunistic yeast Candida albicans. The mechanism of action is still
      unclear. Histatin 5 and more potent synthetic variants, dhvar4 and dhvar5, were
      used to study localization and effects on morphology on the ultra-structural
      level. Although all peptides induced leakage, no association with the plasma
      membrane, indicative for permanent pores, was observed with immuno-gold-labeling.
      Freeze-fracturing showed severe changes of the plasma membrane. Together with,
      for the dhvars, the loss of intracellular integrity, this suggests that leakage
      may be a secondary effect rather than an effect of formation of permanent pores.

PMID- 12182940
TI  - Cloning and characterization of rhesus monkey MCH-R1 and MCH-R2.
AB  - Rhesus monkey MCH-R1 and MCH-R2 receptors were cloned. Amino acid homology is
      98.8% between monkey and human MCH-R1, while monkey and human MCH-R2 are 98%
      homologous. Binding and intracellular signaling characteristics of the monkey
      receptors were compared with the human homologues. The results demonstrate that
      MCH binds to the monkey MCH-R1 receptor with a K(d) of 6.5 nM and monkey MCH-R2
      with a K(d) of 2.2 nM similar to K(d) values for human MCH-R1 and MCH-R2.
      Additionally, monkey MCH-R1 couples through G(i)/G(o) and G(q)-type G proteins
      similar to human MCH-R1 whereas monkey and human MCH-R2 utilize the G(q)
      signaling pathway.

PMID- 12182941
TI  - Regulation of cellular alpha-MSH and beta-endorphin during stimulated secretion
      from intermediate pituitary cells: involvement of aspartyl and cysteine proteases
      in the control of cellular levels of alpha-MSH and beta-endorphin.
AB  - The regulation of cellular levels of alpha-melanocyte stimulating factor (alpha
      MSH) and beta-endorphin in response to stimulated secretion from intermediate
      pituitary cells in primary culture was investigated in this study. Regulation of
      the cell content of alpha-MSH and beta-endorphin occurred in two phases
      consisting of (a) initial depletion of cellular levels of these peptide hormones
      during short-term secretion (3 h) induced by isoproterenol, forskolin, or phorbol
      myristate acetate (PMA) which was followed by (b) long-term (24 h) increases in
      cellular levels of alpha-MSH and beta-endorphin in response to stimulated
      secretion induced by isoproterenol and PMA. In short-term experiments (3 h),
      cellular levels of alpha-MSH and beta-endorphin were reduced by 30-50% during
      stimulated secretion of these peptide hormones by isoproterenol (agonist for the
      beta-adrenergic receptor), forskolin that activates protein kinase A (PKA), and
      PMA that activates protein kinase C (PKC). Moreover, dopamine inhibited
      isoproterenol-induced depletion of cellular alpha-MSH and beta-endorphin. During
      long-term incubation of cells (24 h) with isoproterenol, cellular alpha-MSH and
      beta-endorphin were increased to twice that of controls (unstimulated cells).
      Treatment with PMA for 24 h also increased cellular levels of alpha-MSH and beta
      endorphin. Moreover, cellular levels of alpha-MSH and beta-endorphin were
      decreased during long-term treatment of cells with an aspartyl protease
      inhibitor, pepstatin A, and with the cysteine protease inhibitor E64c. These
      results implicate aspartyl and cysteine proteases in the cellular production of
      alpha-MSH and beta-endorphin that requires proteolytic processing of their common
      precursor proopiomelanocortin (POMC). These findings demonstrate the parallel
      regulation of cellular levels of alpha-MSH and beta-endorphin during their
      cosecretion, which may involve aspartyl and cysteine proteases in the metabolism
      of these peptide hormones.

PMID- 12182942
TI  - Noncompetitive nature of oxytocin antagonists with general structure
      Mpa(1)Xxx(2)Sar(7)Arg(8).
AB  - Eight oxytocin (OT) antagonists with general structure Mpa(1)Sar(7)Arg(8),
      substituted at position 2 with conformationally constrained and bulky amino
      acids, were synthesized and pharmacologically tested. Binding affinities and
      selectivities of compounds for OT, and vasopressin receptor subtypes were
      investigated. In vitro effects of antagonists were evaluated via inhibition of OT
      induced contractions of isolated guinea-pig uterus. The abilities of OT
      antagonists to inhibit spontaneous contractility in 24 h postpartum rat uterus
      were investigated. These peptides exhibited pseudoirreversible pharmacological
      properties, and comprise a novel group of OT antagonists for potential clinical
      use. Their noncompetitive pharmacological nature can be of therapeutic benefit
      through a sustained effect on myometrium.

PMID- 12182943
TI  - Sodium deficiency enhances the behavioral responses to centrally administered
      vasopressin in rats.
AB  - The ability of sodium deficiency to stimulate vasopressin (VP) release was
      examined by determining if sodium deficiency sensitizes the animal to the
      behavioral disruption caused by intraventricular injections of VP. In sodium
      replete rats, intraventricular injections of 50 ng VP on Day 1 had no effect on
      behavior, but this dose elicited abnormal behaviors (barrel rolls, hind-limb
      extensions) when administered on Day 2, indicating a sensitization phenomenon. In
      separate experiments, the first intraventricular injection of 50 ng VP in sodium
      deficient but not in sodium-replete rats also elicited barrel rotations followed
      by hind-limb extension. Intraventricular injection of VP also disrupted motor
      behavior in sodium-replete rats that had multiple prior experiences with sodium
      deficiency but not in naive rats. These results show that sodium deficiency can
      mimic the effect of central injections of VP in sensitizing the brain to the
      behavioral effects of exogenous VP. This suggests that sodium deficiency induces
      the central release of VP.

PMID- 12182944
TI  - Interactions of human secretin with sterically stabilized phospholipid micelles
      amplify peptide-induced vasodilation in vivo.
AB  - Secretin, a 27-amino acid neuropeptide, is a member of the
      glucagon/secretin/vasoactive intestinal polypeptide (VIP) superfamily of
      amphipathic peptides that elicits transient vasodilation in vivo. The purpose of
      this study was to determine whether association of human secretin with sterically
      stabilized phospholipid micelles (SSM) amplifies the vasorelaxant effects of the
      peptide in the peripheral microcirculation in vivo. We found that secretin in
      saline evoked significant concentration-dependent vasodilation in the intact
      hamster cheek pouch microcirculation (P < 0.05). This response was potentiated
      and prolonged significantly when secretin was associated with SSM (P < 0.05).
      Vasodilation evoked by secretin in saline and secretin in SSM was abrogated by
      VIP(10-28), a VIP receptor antagonist, but not by PACAP(6-38), a PACAP receptor
      antagonist, or Hoe140, a selective bradykinin B(2) receptor antagonist.
      Collectively, these data indicate that self-association of human secretin with
      SSM significantly amplifies peptide vasoreactivity in the intact peripheral
      microcirculation through activation of VIP receptors. We suggest that the
      vasoactive effects of human secretin in vivo are, in part, phospholipid
      dependent.

PMID- 12182945
TI  - Cardiotrophin-1 stimulates endothelin-1 via gp130 in vascular endothelial cells.
AB  - Endothelin-1 (ET-1) is a vasoconstricting and mitogenic peptide released from
      vascular endothelial cells under normal and pathophysiological conditions, and
      synthesis and secretion of ET-1 are stimulated by cytokines. Cardiotrophin-1 (CT
      1) is a new member of the interleukin-6-type cytokines that induce biological
      actions through the glycoprotein (gp) 130. The present study was designed to
      determine the presence of CT-1 and the gp130 cytokine system in vascular
      endothelial cells and to investigate whether CT-1 stimulates synthesis and
      secretion of ET-1 in the vascular endothelial cells. We first sought to determine
      gene expression and immunoreactivity of CT-1, gp130 and ET-1 in cultured canine
      aortic endothelial cells (CAECs) using Northern blot analysis and
      immunocytochemistry, which revealed the presence of CT-1 and gp130 together with
      ET-1 in CAECs. CT-1 increased ET-1 gene expression in CAECs, and stimulated ET-1
      secretion from CAECs in a dose-dependent manner. Furthermore, inhibition of gp130
      by monoclonal antibody attenuated ET-1 secretion from CAECs, suggesting that
      actions of CT-1 on the secretion of ET-1 are mediated through gp130 receptor
      system. The present study, therefore, reports the presence of CT-1 and gp130 in
      vascular endothelial cells and mechanisms of secretion of ET-1 related to this
      cytokine system.

PMID- 12182946
TI  - Angiotensin-(1-7) and bradykinin interaction in diabetes mellitus: in vivo study.
AB  - The interaction between angiotensin-(1-7) (Ang-(1-7)) and bradykinin (BK) was
      determined in the mesentery of anesthetized Wistar alloxan-diabetic and non
      diabetic rats using intravital microscopy. Impaired BK vasodilation observed in
      arterioles of diabetic rats was restored by acute and chronic insulin treatment
      as well as by enalapril. Though capable of potentiating BK in non-diabetic rats,
      Ang-(1-7) did not potentiate BK in diabetic rats. Chronic but not acute insulin
      treatment restored the potentiation, whereas enalapril did not. Potassium channel
      blockade (by tetraethylammonium (TEA)) but not nitric oxide (NO) synthase
      inhibition (by N-omega-nitro-L-arginine-methyl-esther (L-NAME)) abolished the
      restorative effect of insulin. Our data allow us to suggest that the alteration
      observed is restored by insulin by a mechanism involving membrane
      hyperpolarization but not NO release. The beneficial effect of enalapril in
      diabetes might not involve the potentiation of BK by Ang-(1-7).

PMID- 12182947
TI  - Interaction of linear and cyclic peptide antagonists at the human B(2) kinin
      receptor.
AB  - The ligand receptor interactions involving the C-terminal moiety of kinin B(2)
      receptor antagonists Icatibant (H-DArg-Arg-Pro-Hyp-Gly-Thi-Ser-Dtic-Oic-Arg-OH),
      MEN 11270 (H-DArg-Arg-Pro-Hyp-Gly-Thi-c(Dab-Dtic-Oic-Arg)c(7gamma-10alpha)) and a
      series of analogs modified in position 10 were investigated by radioligand
      binding experiments at the wild type (WT) and at the Ser(111)Ala and Ser(111)Lys
      mutant human kinin B(2) receptors. Icatibant and [Lys(10)]-Icatibant maintained
      the same high affinity towards the three receptors. For Icatibant-NH(2),
      [Ala(10)]-Icatibant, MEN 11270 and [Glu(10)]-MEN 11270, the changes in affinity
      at the WT and Ser(111)Lys receptors indicated that the presence of a net positive
      or negative charge at the C-terminal moiety of these peptides caused a decrease
      in affinity to the WT receptor and that Ser(111) residue is in proximity of the
      side chain of residue 10. The changes in affinity measured with [desArg(10)]
      Icatibant and [desArg(10)]-Icatibant-NH(2), moreover, confirmed that a C-terminal
      charge compensation between the positive charge of Arg(10) side chain and the C
      terminal free carboxylic function favours a high affinity interaction.

PMID- 12182948
TI  - Comparative effects of angiotensin IV and two hemorphins on angiotensin
      converting enzyme activity.
AB  - The role of angiotensin IV (AngIV) in the regulation of angiotensin-converting
      enzyme (ACE) was studied in vitro. This study demonstrates that this active
      fragment appeared as a novel endogenous ACE inhibitor. Inhibitory kinetic studies
      revealed that AngIV acts as a purely competitive inhibitor with a K(i) value of
      35 microM. AngIV was found to be quite resistant to ACE hydrolysis opposite to
      hemorphins which are both ACE inhibitors and substrates. In order to confirm a
      putative role of AngIV and hemorphins in the Renin-Angiotensin system (RAS)
      regulation, we studied their influence on AngI conversion. We noticed that 16.7
      microM of both peptides decreased more than 50% of AngI conversion to AngII in
      vitro. The capacity of hemorphins, particularly LVVH-7, and AngIV to inhibit ACE
      activity here suggests a synergistic relation between these two peptides and the
      regulation of RAS.

PMID- 12182949
TI  - The neuropeptide PACAP attenuates beta-amyloid (1-42)-induced toxicity in PC12
      cells.
AB  - Pituitary adenylate cyclase activating polypeptide (PACAP) modulates
      neurotransmission in the central and peripheral nervous systems. In vitro and in
      vivo studies have shown the protective effects of PACAP against neuronal damage
      induced by ischemia and agonists of NMDA-type glutamate receptors. Here, we
      demonstrated that PACAP also protected against neuronal toxicity induced by beta
      amyloid (Abeta) peptide, aggregation of which is a causative factor for
      Alzheimer's disease. PACAP (10(-9)M) rescued 80% of decreased cell viability and
      50% of elevated caspase-3 activity that resulted from exposure of PC12 cells to
      Abeta. PACAP was at least 10(4)-fold more effective than other neuropeptides
      including vasoactive intestinal peptide (VIP) and humanin, which correlated with
      the level of cAMP accumulation. Thus, our results suggested that PACAP attenuates
      Abeta-induced cell death in PC12 cells through an increase in cAMP and that
      caspase-3 deactivation by PACAP is involved in the signaling pathway for this
      neuroprotection.

PMID- 12182950
TI  - Co-localization of hypocretin-1 and hypocretin-2 in the cat hypothalamus and
      brainstem.
AB  - Hypocretin-1 (hcrt-1) and hypocretin-2 (hcrt-2) are two recently discovered
      hypothalamic neuropeptides. In the present study, using double immunofluorescent
      techniques, the co-localization of hcrt-1 and hcrt-2 was examined in neuronal
      soma and fibers/terminals located, respectively, in the cat hypothalamus and
      brainstem. In the hypothalamus, all hcrt-1 positive neuronal soma also displayed
      hcrt-2 immunoreactivity. In the brainstem, both hcrt-1 and hcrt-2 antibodies
      labeled the same fibers/terminals, indicating that hcrt-1 and hcrt-2 co-localize
      not only in the neuronal soma (hypothalamus) but also in their fibers/terminals
      (brainstem). If both peptides are released following neuronal activity, then the
      distinct effects of these peptides in the brain are likely to depend on the types
      of postsynaptic receptors that are activated.

PMID- 12182951
TI  - Bis(31/31')[[Cys(31), Nva(34)]NPY(27-36)-NH(2)]: a neuropeptide Y (NPY) Y(5)
      receptor selective agonist with a latent stimulatory effect on food intake in
      rats.
AB  - The actions of neuropeptide Y (NPY) are mediated by at least six G-protein
      coupled receptors denoted as Y(1), Y(2), Y(3), Y(4), Y(5), and y(6).
      Investigations using receptor selective ligands and receptor knock-out mice
      suggest that NPY effects on feeding are mediated by both Y(1) and Y(5) receptors.
      We have previously shown that Cys-dimers of NPY C-terminal peptides exhibit Y(1)
      selectivity relative to Y(2) receptors. Re-investigation of their selectivity
      with respect to the newly cloned receptors, has identified bis(31/31') [[Cys(31),
      Nva(34)]NPY(27-36)-NH(2)] (BWX-46) as a Y(5) receptor selective agonist. BWX-46
      selectively bound Y(5) receptors, and inhibited cAMP synthesis by Y(5) cells with
      potencies comparable to that of NPY. Moreover, BWX-46 (10 microM) exhibited no
      significant effect on the cAMP synthesis by Y(1), Y(2), and Y(4) cells. Thus, BWX
      46 constitutes the lowest molecular weight Y(5) selective agonist reported to
      date. Intrahypothalamic (i.h.t)-injection of 30 and 40 microg of BWX-46
      stimulated the food intake by rats in a gradual manner, reaching maximal level 8
      h after injection. This response was similar to that exhibited by other Y(5)
      selective agonists, but differed from that of NPY, which exhibited a rapid
      orexigenic stimulus within 1 h. It is suggested that the differences in the
      orexigenic stimuli of NPY and Y(5) agonists may be due to their differences in
      the signal transduction mechanisms.

PMID- 12182952
TI  - Plasma glucagon-like peptide-1 (GLP-1) responses to duodenal fat and glucose
      infusions in lean and obese men.
AB  - It has been suggested that obesity is associated with a reduced glucagon-like
      peptide-1 (GLP-1) response to oral carbohydrate, but not fat. The latter may,
      however, be attributable to changes in gastric emptying. We have assessed plasma
      GLP-1 levels in response to these infusions in lean and obese subjects. Seven
      healthy lean (body mass index (BMI), 19.1-24.6 kg/m(2)) and seven obese (BMI,
      31.3-40.8 kg/m(2)) young men received an intraduodenal infusion of glucose and
      fat for 120 min (2.86 kcal/min) on two separate days. Blood samples for plasma
      GLP-1 were obtained at baseline and every 20 min during the infusion. Plasma GLP
      1 increased during infusion of glucose and fat (P = 0.001), but there were no
      differences between lean and obese subjects, nor the two nutrients. We conclude
      that GLP-1 secretion in response to duodenal infusion of glucose and fat is not
      altered in obese subjects.

PMID- 12182953
TI  - Alterations in GHRH binding and GHRH receptor mRNA in the pituitary of adult
      dw/dw rats.
AB  - Lewis dwarf (dw/dw) rats exhibit growth hormone (GH) deficiency and growth
      retardation linked to a malfunction of GHRH signaling. In this study, GHRH
      receptor (GHRH-R) binding and mRNA in the pituitary of adult male dw/dw and age
      matched normal Lewis rats was measured by radioligand binding assay and real-time
      PCR. Only one of nine pools of dw/dw pituitary membranes revealed detectable
      binding of [His(1), 125I-Tyr(10), Nle(27)]hGHRH(1-32) amide (B(max); 4.3 fmol/mg
      protein). In contrast, GHRH-R binding was 22.4 +/- 2.60 fmol/mg protein in normal
      Lewis rats. mRNA for GHRH-R was detectable in all dw/dw rat pituitaries examined,
      averaging 21% that of Lewis rats. Low expression of GHRH-R reflects reduced GHRH
      R mRNA as well as a possible reduction in translation of the receptor protein.

PMID- 12182954
TI  - The putative somatostatin antagonist, cyclo-(7-aminoheptanoyl-Phe-D-Trp-Lys
      Thr[BZL]), may act as potent antiproliferative agonist.
AB  - The cyclic somatostatin (SST) analogue, cyclo-(7-aminoheptanoyl-Phe-D-Trp-Lys
      Thr[BZL]) (cSSTA), has been widely used as somatostatin antagonist. In the human
      neuroblastoma cell line SH-SY5Y the cyclopeptide acts as a somatostatin receptor
      agonist. Similar to SST, cSSTA inhibits cell proliferation, activates the protein
      tyrosine phosphatase SHP-2, and stimulates the activity of mitogen-activated
      protein kinase. These results suggest that in SH-SY5Y neuroblastoma cells
      somatostatin receptors may exist which exhibit altered antagonist binding
      properties.

PMID- 12182955
TI  - G protein-dependent activation of mast cell by peptides and basic secretagogues.
AB  - Signaling pathways leading to exocytosis and arachidonate release from serosal
      mast cells by basic secretagogues, including cationic peptides, arise from the
      involvement of betagamma subunits from G(i2) and G(i3) GTP-binding proteins. The
      original concept that basic secretagogues directly interact with G proteins
      implicated the entry of secretagogues into mast cells. This has been demonstrated
      only for the neuropeptide substance P. Basic secretagogues might share a common
      mechanism of penetration with the newly described cell-penetrating peptides. The
      involvement of some membrane transporter or non-selective membrane receptor to
      basic secretagogues cannot be excluded.

PMID- 12182956
TI  - Interaction of xenin with the neurotensin receptor of guinea pig enteral smooth
      muscles.
AB  - Xenin, a 25 amino acid peptide, interacts with the neurotensin receptor subtype 1
      of intestinal muscles of the guinea pig. Replacement of the C-terminal Lys-Arg
      peptide bond in xenin 6 by a reduced pseudo-peptide bond augmented binding
      affinity to isolated jejunal and colonic muscle membranes by factors of 7.7 and
      21.0 respectively; the potency to contract the jejunum and to relax the colon was
      increased by factors of 3.2 and 1.3. The C-terminus Trp-Ile-Leu (WIL) of xenin,
      in contrast to the C-terminus Tyr-Ile-Leu (YIL) of neurotensin, bound
      competitively to the muscle membranes. WIL blocked the contractile action of
      xenin in the jejunum and was synergistic with the relaxing action in the colon.
      The Lys-Arg motif and Trp in the C-terminus of xenin are essential structures in
      the action of xenin on the enteral smooth muscle receptors.

PMID- 12182957
TI  - Proceedings of the Workshop on New Perspectives on Therapeutic Use of
      Endocannabinoids. Madrid, Spain. October 17-18, 2000.

PMID- 12182958
TI  - From cannabis to cannabinergics: new therapeutic opportunities.
AB  - The molecular basis of cannabinoid activity is better understood since the
      discovery of the CB(1) receptor in the mammalian brain and the CB(2) receptor in
      peripheral tissues. Subsequently, an endogenous CB(1) receptor ligand,
      arachidonylethanolamide (anandamide), was isolated from porcine brain and shown
      to be metabolized by the enzyme arachidonylethanolamide amidohydrolase or fatty
      acid amide hydrolase. Recently, we have characterized a reuptake system for the
      transport of anandamide across the cell membrane, and have shown that selective
      inhibition of this transporter is associated with analgesia and peripheral
      vasodilation. The four cannabinoid system proteins, including the CB(1) and CB(2)
      receptors, fatty acid amide hydrolase, and the anandamide transporter, are
      excellent targets for the development of novel medications for various
      conditions, including pain, immunosuppression, peripheral vascular disease,
      appetite enhancement or suppression, and motor disorders. During the last decade,
      numerous selective ligands for each of these proteins were designed and
      synthesized. Many of these agents serve as important molecular probes, providing
      structural information about their binding sites, as well as pharmacological
      tools imparting information about the roles of their targets in physiological and
      disease states. All of the above compounds that modulate the functions of the
      endocannabinoid system can be collectively described under the term
      cannabinergics, regardless of chemical classification or type of resultant
      pharmacological action.

PMID- 12182959
TI  - Putative neuroprotective actions of N-acyl-ethanolamines.
AB  - N-Acyl-ethanolamines (NAEs) and their precursors, N-acyl-ethanolamine
      phospholipids (NAPEs), are present in the mammalian brain at levels of a few
      hundred picomoles/gram tissue and a few nanomoles/gram tissue, respectively. NAE
      containing arachidonic acid is called anandamide, and it has attracted particular
      attention since it is a partial agonist for the cannabinoid receptors, for which
      2-arachidonoylglycerol is the full agonist. In addition, anandamide may also
      activate the vanilloid receptor. Anandamide usually amounts to 1-10% of NAEs, as
      the vast majority of N-acyl groups are saturated and monounsaturated fatty acids.
      Formation of NAPE and NAE is catalyzed by an N-acyltransferase and an NAPE
      hydrolyzing phospholipase D, respectively, two enzymes that have been
      characterized only preliminary. Interestingly, NAPEs and NAEs accumulate in the
      brain in response to neurodegenerative insults at a time when other phospholipids
      are subjected to rapid degradation. This is an important biosynthetic aspect of
      NAPE and NAE, as NAEs may be neuroprotective by a number of different mechanisms
      involving both receptor activation and non-receptor-mediated effects, e.g. by
      binding to cannabinoid receptors and interfering with ceramide turnover,
      respectively.

PMID- 12182960
TI  - Cannabinoid analgesia.
AB  - During the last decade, rigorous scientific methods have been applied to
      determine the effects of cannabinoids on nociceptive neurotransmission.
      Cannabinoids have been observed to markedly decrease signalling in specific
      neural pathways that transmit messages about pain. These effects were found to be
      due to the suppression of spinal and thalamic nociceptive neurons, and
      independent of any actions on either the motor system or sensory neurons that
      transmit messages related to non-nociceptive stimulation. Spinal, supraspinal,
      and peripheral sites of cannabinoid analgesia have been identified. The discovery
      of endocannabinoids raised the question of their natural role in pain. Multiple
      lines of evidence indicate that endocannabinoids serve naturally to suppress
      pain. While it is now clear that cannabinoids suppress nociceptive
      neurotransmission, more work is needed to establish the clinical utility of these
      compounds. The few human studies conducted to date produced mixed results, with
      more promising findings coming from studies of clinical pain as compared with
      experimental pain. The therapeutic potential of cannabinoids remains an important
      topic for future investigations.

PMID- 12182961
TI  - The endogenous cannabinoid system and the basal ganglia. biochemical,
      pharmacological, and therapeutic aspects.
AB  - New data strengthen the idea of a prominent role for endocannabinoids in the
      modulation of a wide variety of neurobiological functions. Among these, one of
      the most important is the control of movement. This finding is supported by 3
      lines of evidence: (1) the demonstration of a powerful action, mostly inhibitory
      in nature, of synthetic and plant-derived cannabinoids and, more recently, of
      endocannabinoids on motor activity; (2) the presence of the cannabinoid CB(1)
      receptor subtype and the recent description of endocannabinoids in the basal
      ganglia and the cerebellum, the areas that control movement; and (3) the fact
      that CB(1) receptor binding was altered in the basal ganglia of humans affected
      by several neurological diseases and also of rodents with experimentally induced
      motor disorders. Based on this evidence, it has been suggested that new synthetic
      compounds that act at key steps of endocannabinoid activity (i.e., more-stable
      analogs of endocannabinoids, inhibitors of endocannabinoid reuptake or
      metabolism, antagonists of CB(1) receptors) might be of interest for their
      potential use as therapeutic agents in a variety of pathologies affecting
      extrapyramidal structures, such as Parkinson's and Huntington's diseases.
      Currently, only a few data exist in the literature studying such relationships in
      humans, but an increasing number of journal articles are revealing the importance
      of this new neuromodulatory system and arguing in favour of the funding of more
      extensive research in this field. The present article will review the current
      knowledge of this neuromodulatory system, trying to establish the future lines
      for research on the therapeutic potential of the endocannabinoid system in motor
      disorders.

PMID- 12182962
TI  - Study of cannabinoid dependence in animals.
AB  - Different animal models have been used to clarify the consequences of chronic
      exposure to cannabinoid agonists and their abuse liability. Following the chronic
      administration of cannabinoids, tolerance develops to most of their
      pharmacological effects. The development of cannabinoid tolerance is particularly
      rapid, and seems to be due to pharmacodynamic events. A cross-tolerance among
      different exogenous cannabinoid agonists has been reported. Somatic signs of
      spontaneous withdrawal have not been reported after chronic Delta(9)
      tetrahydrocannabinol (THC) treatment, but were observed after chronic treatment
      with the cannabinoid agonist WIN-55,212-2. The administration of the CB(1)
      cannabinoid antagonist SR141716A in animals chronically treated with THC and
      other cannabinoid agonists precipitated somatic manifestations of withdrawal. The
      potential ability of anandamide to induce physical dependence has not been
      clarified. Subjective drug effects of cannabinoids have been reported by drug
      discrimination studies, which show cross discrimination among different natural
      and synthetic agonists. The rewarding effects of cannabinoids have been revealed
      by using several paradigms: place conditioning, intracranial self-stimulation,
      and self-administration. Cannabinoids have been reported to lower intracranial
      self-stimulation thresholds in rats. However, particular experimental conditions
      are required to induce conditioned place preference with cannabinoids. Numerous
      studies have shown that THC is unable to induce a self-administration behaviour
      in animals. However, WIN-55,212-2 was intravenously self-administered in mice,
      and monkeys that had a previous history of cocaine self-administration also self
      administered THC. The mesolimbic dopaminergic system seems to be the substrate
      for the rewarding properties of cannabinoids.

PMID- 12182963
TI  - Cannabinoids and multiple sclerosis.
AB  - There is a growing amount of evidence to suggest that cannabis and individual
      cannabinoids may be effective in suppressing certain symptoms of multiple
      sclerosis and spinal cord injury, including spasticity and pain. Anecdotal
      evidence is to be found in newspaper reports and also in responses to
      questionnaires. Clinical evidence comes from trials, albeit with rather small
      numbers of patients. These trials have shown that cannabis, Delta(9)
      tetrahydrocannabinol, and nabilone can produce objective and/or subjective relief
      from spasticity, pain, tremor, and nocturia in patients with multiple sclerosis
      (8 trials) or spinal cord injury (1 trial). The clinical evidence is supported by
      results from experiments with animal models of multiple sclerosis. Some of these
      experiments, performed with mice with chronic relapsing experimental allergic
      encephalomyelitis (CREAE), have provided strong evidence that cannabinoid-induced
      reductions in tremor and spasticity are mediated by cannabinoid receptors, both
      CB(1) and CB(2). Endocannabinoid concentrations are elevated in the brains and
      spinal cords of CREAE mice with spasticity, and in line with this observation,
      spasticity exhibited by CREAE mice can be ameliorated by inhibitors of
      endocannabinoid membrane transport or enzymic hydrolysis. Research is now needed
      to establish whether increased endocannabinoid production occurs in multiple
      sclerosis. Future research should also be directed at obtaining more conclusive
      evidence about the efficacy of cannabis or individual cannabinoids against the
      signs and symptoms of these disorders, at devising better modes of administration
      for cannabinoids and at exploring strategies that maximize separation between the
      sought-after therapeutic effects and the unwanted effects of these drugs.

PMID- 12182964
TI  - Cannabinoids and cell fate.
AB  - Cannabinoids recently have been shown to control the cell survival/death
      decision. Thus, cannabinoids induce growth arrest or apoptosis in a number of
      transformed neural and non-neural cells in culture. In addition, cannabinoid
      administration induces regression of malignant gliomas in rodents by a mechanism
      that may involve sustained ceramide generation and extracellular signal-regulated
      kinase activation. In contrast, most of the experimental evidence indicates that
      cannabinoids may protect normal neurons from toxic insults, such as glutamatergic
      overstimulation, ischaemia, and oxidative damage. Regarding immune cells, low
      doses of cannabinoids may enhance proliferation, whereas high doses of
      cannabinoids usually induce growth arrest or apoptosis. The potential therapeutic
      applications of these findings are discussed.

PMID- 12182965
TI  - Tetrahydrocannabinol and endocannabinoids in feeding and appetite.
AB  - The physiological control of appetite and satiety, in which numerous
      neurotransmitters and neuropeptides play a role, is extremely complex. Here we
      describe the involvement of endocannabinoids in these processes. These endogenous
      neuromodulators enhance appetite in animals. The same effect is observed in
      animals and in humans with the psychotropic plant cannabinoid Delta(9)
      tetrahydrocannabinol, which is an approved appetite-enhancing drug. The CB(1)
      cannabinoid receptor antagonist SR141716A blocks the effects on feeding produced
      by the endocannabinoids. If administered to mice pups, this antagonist blocks
      suckling. In obese humans, it causes weight reduction. Very little is known about
      the physiological and biochemical mechanisms involved in the effects of Delta(9)
      tetrahydrocannabinol and the cannabinoids in feeding and appetite.

PMID- 12182966
TI  - Cardiovascular effects of cannabinoids.
AB  - The prototypic endocannabinoid, anandamide, and synthetic analogues have been
      shown to elicit pressor and depressor effects, bradycardia, vasorelaxation, and
      inhibition of neurotransmission in the central and peripheral nervous systems.
      Cannabinoid-mediated inhibition of neurotransmission is mediated by inhibition of
      voltage-gated Ca(2+) channels and adenylyl cyclase and activation of inwardly
      rectifying K(+) channels. The precise mechanisms underlying the vasorelaxant
      actions of cannabinoids are currently unclear, but might involve both receptor
      dependent and -independent and endothelium-dependent and -independent pathways.
      Mechanisms proposed have included the release of endothelial autacoids,
      activation of myoendothelial gap junctions, activation of the Na(+) pump,
      activation of K(+) channels, inhibition of Ca(2+) channels, and activation of
      vanilloid receptors, leading to the release of sensory neurotransmitters.
      Pathophysiologically, the vasodilator actions of endocannabinoids have been
      implicated in the hypotension associated with both septic and haemorrhagic shock,
      but their physiological significance remains to be determined.

PMID- 12182968
TI  - Pediatric Hodgkin's disease--up, up, and beyond.
AB  - Juan A. del Regato, 1909-1999, was a superb clinician-educator who recognized the
      radiocurability of Hodgkin's disease but questioned treatment without late
      effects, particularly in children. The remarkable progress in pediatric Hodgkin's
      disease today is a tribute to this influential pioneer, who served as a role
      model to many. Combined modality therapy using low-dose, involved-field radiation
      and multiagent chemotherapy today results in a 5-year relative survival rate of
      94% among American children with Hodgkin's disease. However, several areas hold
      promise for future advances, including a new pathology classification and biology
      studies that distinguish classic Hodgkin's disease from other lymphomas; new
      noninvasive staging techniques, including 18F-fluorodeoxyglucose-positron
      emission tomography; the definition of risk groups to segregate low-,
      intermediate-, and high-risk groups on the basis of a prognostic index,
      facilitating risk-adapted therapy; and myeloablative therapy followed by
      hematopoietic stem cell transplantation. Currently used for children with
      relapse, it is associated with a 5-year survival of 65% and should be considered
      as the initial therapy for high-risk groups. Idiopathic diffuse pulmonary
      toxicity after autologous transplantation is high among children with an atopic
      history; thus, atopy should be considered when selecting children appropriate for
      transplantation. Finally, novel therapies, such as the anti-CD20 antibody,
      rituximab, may be useful for children with CD20+, lymphocyte-predominant
      Hodgkin's disease. The universal goal of cure without late effects is realistic
      for almost all children with Hodgkin's disease today.

PMID- 12182967
TI  - Cannabinoids in the treatment of glaucoma.
AB  - The leading cause of irreversible blindness is glaucoma, a disease normally
      characterized by the development of ocular hypertension and consequent damage to
      the optic nerve at its point of retinal attachment. This results in a narrowing
      of the visual field, and eventually results in blindness. A number of drugs are
      available to lower intraocular pressure (IOP), but, occasionally, they are
      ineffective or have intolerable side-effects for some patients and can lose
      efficacy with chronic administration. The smoking of marijuana has decreased IOP
      in glaucoma patients. Cannabinoid drugs, therefore, are thought to have
      significant potential for pharmaceutical development. However, as the mechanism
      surrounding their effect on IOP initially was thought to involve the CNS, issues
      of psychoactivity hindered progress. The discovery of ocular cannabinoid
      receptors implied an explanation for the induction of hypotension by topical
      cannabinoid applications, and has stimulated a new phase of ophthalmic
      cannabinoid research. Featured within these investigations is the possibility
      that at least some cannabinoids may ameliorate optic neuronal damage through
      suppression of N-methyl-D-aspartate receptor hyperexcitability, stimulation of
      neural microcirculation, and the suppression of both apoptosis and damaging free
      radical reactions, among other mechanisms. Separation of therapeutic actions from
      side-effects now seems possible through a diverse array of novel chemical,
      pharmacological, and formulation strategies.

PMID- 12182969
TI  - A Phase III placebo-controlled trial of oral pilocarpine in patients undergoing
      radiotherapy for head-and-neck cancer.
AB  - PURPOSE: To test the hypothesis that the use of oral pilocarpine during and after
      radiotherapy (RT) for head-and-neck cancer would reduce the symptoms of post-RT
      xerostomia. METHODS AND MATERIALS: One hundred thirty patients were randomized in
      a double-blind method to receive either pilocarpine (5-mg tablets) or placebo
      three times daily starting on Day 1 of RT and continuing for 1 month after
      treatment. The eligibility criteria included a planned dose of >50 Gy as radical
      or postoperative RT for head-and-neck cancer, with at least 50% of both parotid
      glands included in the treatment fields. The primary outcome measure was the
      severity of xerostomia as assessed by a patient-completed linear analog scale 3
      months after RT. Secondary outcome measures included quality of life during
      therapy (as assessed by the McMaster University Head-and-Neck Questionnaire) and
      severity of mucositis during RT (as assessed using Radiation Therapy Oncology
      Group scales). RESULTS: No difference was observed between the pilocarpine
      treated patients and the placebo group in the severity of xerostomia score as
      assessed by linear analog scale at baseline and 1, 3, and 6 months after
      treatment (repeated measures analysis, p = 0.92). No difference was apparent in
      the severity of mucositis during RT; 56.3% of patients receiving pilocarpine had
      Grade III/IV mucositis compared with 50.8% treated with placebo. No difference in
      quality of life was noted between the treatment groups during or after RT. The
      questionnaire score at 3 months after RT was 5.0 (SD 1.0). in the pilocarpine
      group and 4.9 (SD 0.9) in the placebo group. CONCLUSION: We were unable to detect
      a beneficial effect of pilocarpine on RT-induced xerostomia when administered
      during RT for head-and-neck cancer.

PMID- 12182970
TI  - Dose escalation using twice-daily radiotherapy for nasopharyngeal carcinoma: does
      heavier dosing result in a happier ending?
AB  - PURPOSE: To present our experience using a twice-daily radiotherapy (RT)
      technique, including hyperfractionated and accelerated-hyperfractionated RT, on
      nasopharyngeal carcinoma (NPC) patients. The dose to the primary tumor was
      increased in the hope that local control could be increased without the cost of
      increased late complications. We analyzed acute and late complications and local
      control and compared the results with the results of NPC patients treated during
      the same period using conventional once-daily RT. METHODS AND MATERIALS: Between
      October 1991 and July 1998, 222 histologically confirmed, Stage M0, previously
      unirradiated NPC patients completed RT at our hospital. Most patients had
      American Joint Committee on Cancer (AJCC) 1992 Stage III and IV disease. Among
      them, 88 received altered fractionated, twice-daily RT; 76 patients received
      hyperfractionated RT and 12 accelerated-hyperfractionated RT. The remaining 134
      patients received a conventional once-daily regimen. Hyperfractionated RT was
      delivered using 120 cGy b.i.d. separated by 6-h intervals throughout the course.
      For the accelerated-hyperfractionated patients, 160 cGy b.i.d. was given, also at
      6-h intervals. The median dose in the twice-daily group was 7810 cGy (range 6840
      8200). In the once-daily regimen, RT was delivered using 180-200 cGy q.d. The
      median tumor dose to the primary tumor was 7000 cGy (range 6560-8100) given
      during about 8 weeks. The median follow-up time was 70.5 and 72 months for the
      twice-daily and once-daily groups, respectively. RESULTS: The incidence of acute
      toxicities was higher in the twice-daily group with more severe mucositis and
      moist desquamation than in the once-daily group. Both groups had a similar
      incidence of late complications, except for 3 cases of temporal lobe necrosis in
      the twice-daily group, all in patients treated with 160 cGy. No difference was
      noted in recurrence-free local control between the two groups when the individual
      T stage was compared using AJCC 1992 or 1997 criteria (p = 0.51 and 0.59,
      respectively). The 5-year local control rate for T1-3 (AJCC 1997) was 93.2% for
      the twice-daily group and 86.4% for the once-daily group (p = 0.45). In Stage T4
      (AJCC 1997) patients, the local control rate dropped drastically to 43.5% and
      36.9% for the twice-daily and once-daily groups, respectively. The overall neck
      control rate at 5 years was 87.3% and 80.3% for the twice-daily and once-daily
      patients, respectively (p = 0.16). The overall locoregional control rate was
      82.7% for the twice-daily group and 66.6% for the once-daily group. The
      difference was again not statistically significant, but showed a tendency in
      favor of the twice-daily regimen (p = 0.055). Locoregional failure occurred
      mainly in Stage T4 patients with central nervous invasion for whom local control
      was particularly poor, with a failure rate of about 60%. CONCLUSION: The present
      data suggest that NPC patients can be safely treated using a 120-cGy twice-daily
      program with a 6-h interval up to 8000 cGy. The accelerated-hyperfractionated
      technique is not recommended. A large discrepancy in local control between
      patients with T1-3 and T4 disease was noted. For T1-3 disease, an excellent local
      control rate >90% was achieved using the twice-daily regimen. In contrast,
      failure in the T4 patients was as high as 55% in the twice-daily group and
      reached 65% in the once-daily group. More rigorous treatment is needed using
      either additional dose escalation or other strategies for T4 NPC patients. With a
      dose escalation of 1000 cGy using 120-cGy twice-daily RT, a trend toward better
      locoregional control and disease-specific survival was noted in the twice-daily
      group. Whether this difference was truly the result of an increased dose needs
      additional confirmation in studies with larger patient numbers.

PMID- 12182971
TI  - Pilot study of impedance-controlled microcurrent therapy for managing radiation
      induced fibrosis in head-and-neck cancer patients.
AB  - PURPOSE: To evaluate the effectiveness of impedance-controlled microcurrent
      therapy for managing treatment sequelae in head-and-neck cancer patients. METHODS
      AND MATERIALS: Between January 1998 and June 1999, 26 patients who were
      experiencing late effects of radiotherapy were treated b.i.d. with impedance
      controlled microcurrent therapy for 1 week. Objective range-of-motion
      measurements were made for cervical rotation, extension/flexion, and lateral
      flexion before therapy, at the end of each treatment day, and monthly for 3
      months. In addition, each patient's subjective complaints were tabulated before
      treatment and reevaluated at the last follow-up visit. No additional physical
      therapy or electrical stimulation was permitted during the follow-up period.
      RESULTS: At the end of the course of microcurrent therapy, 92% of the 26 patients
      exhibited improved cervical rotation, 85% had improved cervical
      extension/flexion, and 81% had improved cervical lateral flexion. Twenty-two
      patients returned for the 3-month follow-up visit. Of these, 91% had maintained a
      cervical rotation range of motion greater than their pretherapy measurements.
      Eighty-two percent maintained improved cervical extension/flexion and 77%
      maintained improved lateral flexion. When the range-of-motion measurements were
      stratified by pretreatment severity (severe, moderate, mild, or asymptomatic),
      the degree of improvement directly correlated with the severity. Thus, patients
      who had more severe initial symptoms experienced a higher percentage of
      improvement than did those with milder symptoms. For these patients, the cervical
      rotation range of motion changed from a baseline of 59 degrees +/- 12 degrees to
      83 degrees +/- 14 degrees at 3 months; flexion/extension improved from 47 degrees
      +/- 10 degrees to 73 degrees +/- 13 degrees; and lateral flexion went from 31
      degrees +/- 7 degrees to 48 degrees +/- 9 degrees. Some patients also reported
      symptom improvement for tongue mobility, facial asymmetry, xerostomia,
      cervical/facial muscle spasms, trismus, and soft tissue tenderness. No adverse
      effects were observed. CONCLUSION: Impedance-controlled microcurrent therapy
      shows promise for remediation of range-of-motion limitations arising as late
      effects of radiotherapy for head-and-neck cancer. Additional studies are needed
      to validate these preliminary results and to optimize the microcurrent treatment
      protocol, particularly with respect to treatment schedules and combining
      microcurrent therapy with physical and/or drug therapy.

PMID- 12182972
TI  - Proton beam stereotactic radiosurgery of vestibular schwannomas.
AB  - PURPOSE: The proton beam's Bragg peak permits highly conformal radiation of skull
      base tumors. This study, prompted by reports of transient (30% each) and
      permanent (10% each) facial and trigeminal neuropathy after stereotactic
      radiosurgery of vestibular schwannomas with marginal doses of 16-20 Gy, assessed
      whether proton beam radiosurgery using a marginal dose of only 12 Gy could
      control vestibular schwannomas while causing less neuropathy. METHODS AND
      MATERIALS: Sixty-eight patients (mean age 67 years) were treated between 1992 and
      1998. The mean tumor volume was 2.49 cm(3). The dose to the tumor margin (70%
      isodose line) was 12 Gy. The prospectively specified follow-up consisted of
      neurologic evaluation and MRI at 6, 12, 24, and 36 months. RESULTS: After a mean
      clinical follow-up of 44 months and imaging follow-up of 34 months in 64
      patients, 35 tumors (54.7%) were smaller and 25 (39.1%) were unchanged (tumor
      control rate 94%; actuarial control rate 94% at 2 years and 84% at 5 years).
      Three tumors enlarged: one shrank after repeated radiosurgery, one remained
      enlarged at the time of unrelated death, and one had not been imaged for 4 years
      in a patient who remained asymptomatic at last follow-up. Intratumoral hemorrhage
      into one stable tumor required craniotomy that proved successful. Thus, 97% of
      tumors required no additional treatment. Three patients (4.7%) underwent shunting
      for hydrocephalus evident as increased ataxia. Of 6 patients with functional
      hearing ipsilaterally, 1 improved, 1 was unchanged, and 4 progressively lost
      hearing. Cranial neuropathies were infrequent: persistent facial hypesthesia (2
      new, 1 exacerbated; 4.7%); intermittent facial paresthesias (5 new, 1
      exacerbated; 9.4%); persistent facial weakness (2 new, 1 exacerbated; 4.7%)
      requiring oculoplasty; transient partial facial weakness (5 new, 1 exacerbated;
      9.4%), and synkinesis (5 new, 1 exacerbated; 9.4%). CONCLUSION: Proton beam
      stereotactic radiosurgery of vestibular schwannomas at the doses used in this
      study controls tumor growth with relatively few complications.

PMID- 12182973
TI  - Preirradiation endocrinopathies in pediatric brain tumor patients determined by
      dynamic tests of endocrine function.
AB  - PURPOSE: To prospectively evaluate pediatric patients with localized primary
      brain tumors for evidence of endocrinopathy before radiotherapy (RT). METHODS AND
      MATERIALS: Seventy-five pediatric patients were evaluated with the arginine
      tolerance test and L-dopa test for growth hormone secretory capacity and
      activity; thyroid-stimulating hormone surge and thyrotropin-releasing hormone
      stimulation test for the hypothalamic-thyroid axis; the 1-microg
      adrenocorticotropin hormone (ACTH) and metyrapone test for ACTH reserve; and,
      depending on age, a gonadotropin-releasing hormone stimulation test to determine
      gonadotropin response. The study included 38 male and 37 female patients, age 1
      21 years with ependymoma (n = 35), World Health Organization (WHO) Grade I-II
      astrocytoma (n = 18), WHO Grade III-IV astrocytoma (n = 10), craniopharyngioma (n
      = 7), optic pathway tumor (n = 4), and germinoma (n = 1). Seven patients
      receiving dexamethasone at the time of the evaluation were excluded from the
      final analysis. RESULTS: Of 68 assessable patient, 45 (66%) had evidence of
      endocrinopathy before RT, including 15 of 32 patients (47%) with posterior fossa
      tumors. Of the 45 patients, 38% had growth hormone deficiency, 43% had thyroid
      stimulating hormone secretion abnormality, 22% had an abnormality in ACTH
      reserve, and 13% had an abnormality in age-dependent gonadotropin secretion.
      CONCLUSION: The incidence of pre-RT endocrinopathy in pediatric brain tumor
      patients is high, including patients with tumors not adjacent to the hypothalamic
      pituitary unit. These data suggest an overestimation in the incidence of
      radiation-induced endocrinopathy. Baseline endocrine function should be
      determined for brain tumor patients before therapy. The potential for radiation
      induced endocrinopathy alone cannot be used as an argument for alternatives to RT
      for most patients. Pre-RT endocrinopathy may be an early indicator of central
      nervous system damage that will influence the functional outcome unrelated to RT.

PMID- 12182974
TI  - Long-term follow-up of RTOG 88-05: twice-daily external irradiation with
      brachytherapy for carcinoma of the cervix.
AB  - PURPOSE: To evaluate the efficacy and toxicity of twice-daily external
      irradiation to the pelvis with brachytherapy for carcinoma of the cervix in a
      long-term follow-up study. METHODS AND MATERIALS: This study was designed to
      administer twice-daily irradiation doses of 1.2 Gy to the pelvis, 5 d/wk.
      Radiotherapy also included one or two low-dose-rate intracavitary implants, to
      deliver a total minimal dose of 85 Gy to point A and 65 Gy to the lateral pelvic
      lymph nodes. RESULTS: Eighty-one patients with clinical Stage IB-IVA carcinoma of
      the cervix were enrolled in this prospective, single arm, Phase I/II study.
      Hyperfractionated irradiation was completed in 88%. Brachytherapy was given in
      two implants in 46% and in one implant in 54%. Six patients had acute Grade 3
      toxicities. The cumulative rate of Grade 3 and 4 late effects for patients with
      Stage IB2, IIA, and IIB disease was 7% at 3 years, 7% at 5 years, and 10% at 8
      years. For patients with Stage III and IVA disease, the rate of late toxicities
      (Grades 3 and 4) was 7% at 3 years and 12% at 5 years. The site of first failure
      was in the pelvis in 41%, para-aortic or supraclavicular lymph nodes in 6%, and
      other distant metastatic sites in 14%. The absolute survival rate was 61% at 3
      years, 48% at 5 years, and 45% at 8 years. The disease-free survival rate was 43%
      at 3 years, 38% at 5 years, and 33% at 8 years. CONCLUSION: The results suggest
      that, combined with brachytherapy, hyperfractionated irradiation to total
      parametrial doses about 10% greater than doses administered with standard
      fractionation pelvic irradiation was tolerated and at least appears to be as
      effective as standard fractionation pelvic irradiation.

PMID- 12182975
TI  - Evaluation of the effect of routine packed red blood cell transfusion in anemic
      cervix cancer patients treated with radical radiotherapy.
AB  - PURPOSE: It is well established that anemia predicts diminished radiocurability
      in cervix cancer. However, the therapeutic benefit of measures to correct the
      anemia remains controversial. The objective of this study was to determine the
      impact of routine transfusion in patients with hemoglobin level (hb-l) < or =11
      g/dl. METHODS AND MATERIALS: Since 1985, it has been departmental policy to
      attempt to correct hb-l < or =11 g/dl before and/or during radiotherapy by red
      blood cell transfusion (RBCT) in patients undergoing radical radiotherapy for
      primary cervix cancer. To assess the benefit of RBCT, the charts of 204 patients
      (FIGO: IB-IV) treated until 1997 were reviewed. Parameters analyzed for their
      impact on disease-specific survival (DSS), pelvic control (PC), and metastases
      free survival (MFS) included pretreatment hb-l, treatment hb-l, stage, tumor
      size, and lymph node status. To determine any differences in outcome according to
      type of anemia, a separate analysis was performed, grouping patients by cause of
      anemia (tumor vs. other medical illness related). RESULTS: Each of the parameters
      tested was significantly correlated with the end points studied in univariate
      analysis. Patients whose hb-l were corrected (18.5%) had an outcome that did not
      differ significantly from that of nontransfused patients, whereas DSS, PC, and
      MFS (all: p < 0.001) were significantly decreased in nonresponders to RBCT.
      Subgroup analysis showed no impact of hb-l in patients with other medical illness
      related anemia (n = 12). In multivariate analysis treatment, but not
      pretreatment, hb-l remained predictive for DSS, PC, and MFS. Persistent anemia
      was associated with a significantly increased risk of death (relative risk: 2.1)
      and pelvic failure (relative risk: 2.4) compared with nontransfused patients. If
      only patients with tumor anemia were considered, the respective risks increased
      (2.7; 3.6). None of the patients with other causes of anemia recurred, whether or
      not their hb-l was maintained. Assessment of the therapeutic gain in patients who
      responded to RBCT showed improved PC (p = 0.02) and a trend toward increased DSS
      (p = 0.06), but no effect on MFS after adjustment for tumor size and lymph node
      status. CONCLUSION: Treatment hb-l, in addition to tumor size and lymph node
      status, independently predicted outcome. Although our final multivariate analysis
      showed a therapeutic benefit for patients whose hb-l was corrected, the response
      to RBCT was disappointing. Results of our subgroup analysis suggest that the
      cause of anemia in patients with cervical cancer warrants in-depth investigation.

PMID- 12182976
TI  - Long-term results of low-dose-rate interstitial-intracavitary brachytherapy in
      the treatment of carcinoma of the cervix.
AB  - PURPOSE: Brachytherapy plays a major role in the treatment of patients with
      carcinoma of the cervix. However, routine intracavitary brachytherapy may not be
      feasible or adequate to treat locally advanced disease. The purpose of this
      retrospective study (spanning a 20-year period) was to determine the outcome of
      interstitial low-dose-rate brachytherapy in the treatment of bulky or locally
      advanced cervical cancer. The long-term survival and safety of this technique
      were evaluated, along with its impact on local and locoregional control, disease
      free survival, and complications. METHODS AND MATERIALS: A total of 185
      previously untreated patients with cervical cancer were treated between 1977 and
      1997. According to the International Federation of Gynecology and Obstetrics
      classification, 21 patients had Stage IB (barrel), 77 Stage II, 77 Stage III, and
      10 Stage IV disease. All patients were treated by a combination of external
      megavoltage irradiation to the pelvis to a dose of 5040 cGy followed by
      interstitial-intracavitary implants to a dose of 40-50 Gy to the implanted volume
      in two applications. RESULTS: Clinical local control was achieved in 152 (82%) of
      the 185 patients. A 5-year disease-free survival rate of 65%, 67%, 49%, and 17%
      was achieved for patients with Stage IB, II, III, and IV disease, respectively.
      Eighteen (10%) of the 185 patients developed Radiation Therapy Oncology Group
      Grade 3 or 4 late complications. CONCLUSION: Patients with locally advanced
      cervical cancer, or with distorted anatomy, may be treated adequately with
      interstitial brachytherapy to achieve excellent locoregional control and a
      reasonable chance of cure with acceptable morbidity.

PMID- 12182977
TI  - Is there a difference in outcome between stage I-II endometrial cancer of
      papillary serous/clear cell and endometrioid FIGO Grade 3 cancer?
AB  - PURPOSE: Several reports in the literature have shown that, compared with
      endometrioid adenocarcinoma, patients with papillary serous (PS) and clear cell
      (CC) histologic features do worse. However, it is unclear whether the outcome of
      PS/CC cancer is different from that of poorly differentiated endometrioid cancer.
      The purpose of this study was to compare the outcome between PS/CC and
      endometrioid International Federation of Gynecology and Obstetrics (FIGO) Grade 3
      cancer and was limited to patients with Stage I-II uterine carcinoma. METHODS AND
      MATERIALS: Between November 1987 and September 1999, 83 patients with Stage I
      endometrial cancer and Stage II occult endometrial cancer were treated with
      simple hysterectomy and high-dose-rate intravaginal brachytherapy. Forty-one
      patients (49%) had FIGO Grade 3 endometrioid tumors (Group 1) and 42 (51%) had
      PS/CC histologic features (Group 2). The mean age was 63 years (range 30-89).
      Comprehensive surgical staging was done in 23 (28%) of 83 patients. Capillary
      space-like invasion (CSLI) was seen in 24 (29%) of 83 patients. The median dose
      of intravaginal brachytherapy when used alone was 21 Gy in 3 fractions.
      Additional external beam radiotherapy was given to 42 (51%) of 83 patients to 45
      Gy. The two groups were balanced with regard to age, race, comprehensive surgical
      staging, amount of myometrial involvement, CSLI, lower uterine segment
      involvement, cervical involvement, and use of external beam radiotherapy. The
      median follow-up was 46 months (range 4-147). RESULTS: The pattern of relapse was
      as follows: vagina/pelvis in 5 of 14 patients, lungs in 8 of 15, intra-abdominal
      in 4 of 12, and supraclavicular lymph nodes in 1 of 14. One of the four intra
      abdominal disseminations was in Group 1 and the other three in Group 2 (p = 0.6).
      The 5-year vaginal/pelvic control, disease-free survival (DFS), and overall
      survival (OS) rate was 93% (95% confidence interval [CI] 87-99%), 79% (95% CI 69
      89%), and 74% (95% CI 64-85%), respectively. No significant difference in outcome
      was found between Groups 1 and 2. The 5-year vaginal/pelvic control rate was 97%
      (95% CI 91-100%) in Group 1 compared with 90% (95% CI 81-99%) in Group 2 (p =
      0.2). The 5-year DFS rate was 79% (95% CI 64-95%) in Group 1 vs. 78% (95% CI 65
      92%) in Group 2 (p = 0.6), and the 5-year OS rate was 71% (95% CI 55-87%) in
      Group 1 vs. 79% (95% CI 66-92%) in Group 2 (p = 0.3). The influence on outcome of
      age, race, comprehensive surgical staging, CSLI, amount of myometrial invasion,
      cervical involvement, lower uterine segment involvement, and presence of pure PS
      or CC histologic features was evaluated. On multivariate analysis, only CSLI
      correlated with poor DFS (p = 0.04; relative risk 3, 95% CI 1-9) and OS (p =
      0.02; relative risk 3, 95% CI 1-6). CONCLUSION: On the basis of the results of
      this study, no significant difference in outcome exists between patients with
      Stage I-II endometrial cancer with PS/CC histologic features and those with
      similar stage disease, but with FIGO Grade 3 endometrioid histologic features.
      CSLI was the only independent predictor of poor DFS and OS.

PMID- 12182978
TI  - Early clinical experience with anatomy-based inverse planning dose optimization
      for high-dose-rate boost of the prostate.
AB  - PURPOSE: To present an exhaustive dosimetric comparison between three geometric
      optimization methods and our inverse-planning simulated annealing (IPSA)
      algorithm, with two different prescriptions for high-dose-rate (HDR) boost of the
      prostate. The objective of this analysis was to quantify the dosimetric
      advantages of the IPSA algorithm compared with more standard geometric
      optimizations. METHODS AND MATERIALS: Between September 1999 and June 2001, 34
      patients were treated to a dose of 40-44 Gy by external pelvic fields, followed
      by an HDR boost of 18 Gy in 3 fractions. The first 4 patients were treated with
      HDR using geometric optimization, and anatomy-based inverse-planning dose
      optimization was used for the remaining 30 patients. We retrospectively used the
      data from these 30 patients to create HDR dose distributions according to five
      different dose optimization protocols, including our IPSA algorithm. The various
      geometric optimization procedures differed in the way the dwell positions were
      activated and plan normalization was performed. Dose-volume histograms from all
      these plans were analyzed and multiple implant quality indexes extracted.
      RESULTS: The IPSA algorithm provided better clinical tumor volume prescription
      dose coverage than did the geometric optimizations. The average prostate volume
      receiving 100% of the prescribed dose (V100) was 96.3% and 94.5% for IPSA with
      two different prescriptions compared with 92.1%, 92.6%, and 88.8% for the three
      geometric optimization schemes. The average urethra V150 value was 0.0% and 0.7%
      for IPSA with two different prescriptions, and the three geometric optimization
      protocols generated average values of 22.9%, 33.9%, and 38.8%. The bladder and
      rectal dose-volume histograms were similar, although the latest version of the
      IPSA algorithm slightly decreases the dose to these organs at risk because of
      organ-specific dose constraints included in the objective function. CONCLUSION:
      We found that planning an HDR prostate boost could be performed in a fast,
      secure, and effective manner with the IPSA algorithm. We demonstrated that our
      inverse-planning algorithm produces superior HDR plans than more conventional
      geometric optimizations for adenocarcinoma of the prostate. The organs at risk
      protection included in the objective function is a major feature of the algorithm
      and should allow us to escalate the HDR dose to the prostate without increasing
      undesirable side effects.

PMID- 12182979
TI  - Post-nerve-sparing prostatectomy, dose-escalated intensity-modulated
      radiotherapy: effect on erectile function.
AB  - PURPOSE: The advent of widespread prostate-specific antigen screening has
      resulted in more younger, potent men being diagnosed with early-stage, organ
      confined prostate cancer amenable to definitive surgery. Nerve-sparing
      prostatectomy is a relatively new surgical advance in the treatment of prostate
      cancer. Very few data exist on the effect of postoperative radiotherapy (RT) on
      erectile function after nerve-sparing prostatectomy. They are based on
      conventional techniques using moderate doses of radiation, 45-54 Gy. Intensity
      modulated RT (IMRT) is becoming more widespread because it allows dose escalation
      with increased sparing of the surrounding normal tissue. We investigated the
      effect of postprostatectomy, high-dose IMRT on patients' erectile function.
      METHODS AND MATERIALS: A review of patient records found 51 patients treated
      between April 1998 and December 2000 with IMRT after unilateral or bilateral
      nerve-sparing prostatectomy. The pathologic disease stage in these patients was
      T2 in 47.4% and T3 in 52.6%. Postoperatively, 4 patients received hormonal
      ablation consisting of one injection of Lupron Depot (30 mg) 2 months before RT.
      The median age was 65 years (range 46-77) at the time of RT. The prescribed dose
      was 64 Gy (range 60-66). The mean dose was 69.6 Gy (range 64.0-72.3). Erectile
      function was assessed before and after RT by questionnaires. Sexual potency was
      defined as erectile rigidity adequate for vaginal penetration. RESULTS: Of the 51
      patients, 18 (35.3%) maintained their potency and 33 (64.7%) became impotent
      after nerve-sparing prostatectomy. Patients who underwent bilateral nerve-sparing
      prostatectomy had higher rates of postoperative potency than did those who
      underwent unilateral nerve-sparing surgery (72.2% vs. 27.8%; p = 0.025). The
      follow-up for the entire group was 19.5 months. All 18 patients (100%) who were
      potent postoperatively remained potent after RT. The median follow-up for the 18
      potent patients was 27.2 months, significantly longer than that of the impotent
      group, 13.0 months (p <0.001). CONCLUSION: This is the first report on the
      effects of dose-escalated IMRT on men who have undergone nerve-sparing
      prostatectomy. Despite the high dose (mean dose 69.6 Gy) to the prostate bed and
      nerves, postoperative IMRT had no negative effect on erectile function for the
      patients who remained potent after nerve-sparing prostatectomy. Longer term
      follow-up and a larger cohort of patients are warranted to confirm these
      findings.

PMID- 12182981
TI  - Radiotherapy alone in technically operable, medically inoperable, early-stage
      (I/II) non-small-cell lung cancer.
AB  - PURPOSE: To investigate the effectiveness of high-dose, curative radiotherapy
      (RT) given alone in technically operable, but medically inoperable, patients with
      early-stage (I-II) non-small-cell lung cancer (NSCLC). METHODS AND MATERIALS:
      Computerized and manual searches were done to identify published reports dealing
      with curative RT for NSCLC. Relevant studies were identified and the information
      provided therein was extracted regarding patient and treatment characteristics,
      treatment outcome, and various pretreatment and treatment-related factors
      influencing outcome, as well as toxicity and quality-of-life issues. RESULTS:
      Although a large variation of pretreatment and treatment characteristics was
      noted in the available studies, a median survival time of >30 months and a 5-year
      survival rate of up to 30% had been achieved. Accumulated experience seems to
      suggest that doses of at least 65 Gy with standard fractionation, or its
      equivalent when altered fractionation is used, are necessary for control of
      NSCLC. Smaller tumors seem to have a favorable prognosis, and the issue of
      elective nodal RT continues to be controversial. Analyses of patterns of failure
      have clearly identified local failure as the predominant pattern. Although a
      number of potential pretreatment patient- and tumor-related prognostic factors
      have been examined, none has been shown to clearly influence survival. Toxicity
      was usually low, but very high doses (e.g., 80 Gy) given with a conventional
      approach may carry a risk of an excessive rate of side effects. CONCLUSION: High
      dose, curative RT is an effective treatment modality in technically operable, but
      medically inoperable, patients with early-stage NSCLC.

PMID- 12182980
TI  - Pathologic evidence of dose-response and dose-volume relationships for prostate
      cancer treated with combined external beam radiotherapy and high-dose-rate
      brachytherapy.
AB  - PURPOSE: The clinical significance of postradiotherapy (RT) prostate biopsy
      characteristics is not well understood relative to the known prognostic factors.
      We performed a detailed pathologic review of posttreatment biopsy specimens in an
      attempt to clarify their relationship with clinical outcome and radiation dose.
      METHODS AND MATERIALS: Between 1991 and 1998, 78 patients with locally advanced
      prostate cancer were prospectively treated with external beam RT in combination
      with high-dose-rate brachytherapy at William Beaumont Hospital and had post-RT
      biopsy material available for a complete pathologic review. Patients with any of
      the following characteristics were eligible for study entry: pretreatment
      prostate-specific antigen level > or =10.0 ng/mL, Gleason score > or =7, or
      clinical Stage T2b-T3cN0M0. Pelvic external beam RT (46.0 Gy) was supplemented
      with three (1991-1995) or two (1995-1998) ultrasound-guided transperineal
      interstitial (192)Ir high-dose-rate implants. The brachytherapy dose was
      escalated from 5.50 to 10.50 Gy per implant. Post-RT prostate biopsies were
      performed per protocol at a median interval of 1.5 years after RT. All pre- and
      post-RT biopsy specimen slides from each case were reviewed by a single
      pathologist (N.S.G.). The presence and amount of residual cancer, most common RT
      effect score, and least amount RT-effect score were analyzed. The median follow
      up was 5.7 years. Biochemical failure was defined as three consecutive prostate
      specific antigen rises. RESULTS: Forty patients (51%) had residual cancer in the
      post-RT biopsies. The 7-year biochemical control rate was 79% for patients with
      negative biopsies vs. 62% for those with positive biopsies with marked RT damage
      vs. 33% for those with positive biopsies with no or minimal RT damage. A greater
      percentage of positive pre-RT biopsy cores (p = 0.01), lower total RT dose (p =
      0.001), lower dose per implant (p = 0.001), and greater percentage of positive
      post-RT biopsy cores (p = 0.01) were each associated with biochemical failure
      (Cox regression, univariate analysis). For patients with <25% positive post-RT
      biopsy cores, the 7-year biochemical control rate was 81% vs. a 62% biochemical
      control rate for those with 25-49% positive cores and only 32% for those with >
      or =50% positive cores (p = 0.01). On Cox multiple regression analysis, only the
      percentage of positive pre-RT biopsy cores and RT dose remained significantly
      associated with biochemical failure. Of all the factors analyzed, only the
      pretreatment cancer volume and lower RT dose were significantly associated with
      residual cancer and/or residual cancer with no or minimal RT damage. A greater
      percentage of positive pre-RT biopsy cores was associated with both a positive
      post-RT biopsy (p = 0.08) and a greater percentage of positive post-RT biopsy
      cores (p = 0.04). A lower total RT dose was associated with both a positive post
      RT biopsy (p = 0.08) and a greater percentage of positive post-RT biopsy cores (p
      = 0.02). For patients who received <80 Gy (equivalent in 2-Gy fractions), 73% had
      positive post-RT biopsies vs. a 56% biopsy positivity rate for those who received
      84-90 Gy and only 39% for those who received > or =92 Gy (p = 0.07). CONCLUSION:
      Patients with positive post-RT biopsies are more likely to experience biochemical
      failure, especially when the RT damage is minimal. Patients who have a larger
      pretreatment tumor volume or receive a lower RT dose are more likely to
      demonstrate post-RT biopsy positivity and biochemical failure.

PMID- 12182982
TI  - Comparison between continuous accelerated hyperfractionated and late-course
      accelerated hyperfractionated radiotherapy for esophageal carcinoma.
AB  - PURPOSE: To compare the treatment results and toxicity of continuous accelerated
      hyperfractionated (CAHF) and late-course accelerated hyperfractionated (LCAF)
      radiotherapy (RT) for esophageal carcinoma. METHODS AND MATERIALS: Between August
      1996 and March 1999, 101 patients with squamous cell carcinoma of the esophagus
      were randomized into two groups: 49 to the CAHF group and 52 to the LCAF group.
      Patients in the CAHF group received RT at 1.5 Gy/fraction b.i.d. (6-h interval),
      5 d/wk, to a total dose 66 Gy in 44 fractions during 4.4 weeks. The patients in
      the LCAF group received conventional fractionation RT, 1.8 Gy/fraction, to a dose
      of 41.4 Gy in 23 fractions during 4.6 weeks, followed by accelerated
      fractionation RT using reduced fields, b.i.d., at 1.5 Gy/fraction, with a minimal
      interval of 6 h between fractions. The total dose was 68.4 Gy in 41 fraction
      during 6.4 weeks. Patient age, gender, performance score, diet, lesion location,
      lesion length, stage, and fractionation (CAHF or LCAF) were entered into the
      univariate and multivariate analyses. RESULTS: All patients finished the
      treatment course, except for 1 patient in the CAHF group because of severe acute
      esophagitis. The rate of Grade I, II, and III acute bronchitis was 18.4% (9 of
      49), 30.6% (15 of 49), and 8.2% (4 of 49) in the CAHF group and 13.5% (7 of 52),
      21.2% (11 of 52), and 3.8% (2 of 52) in the LCAF group, respectively. However,
      the difference between the two groups was not statistically significant (p =
      0.084). The rate of Grade I, II, III, and IV acute esophagitis was 6.1% (3 of
      49), 32.7% (16 of 49), 46.9% (23 of 49), and 14.3% (7 of 49) in the CAHF group
      and 26.9% (14 of 52), 32.7% (17 of 52), 7.7% (4 of 52), and 1.9% (1 of 52) in the
      LCAF group, respectively. The difference was statistically significant (p <
      0.001). The local control rate at 1, 2, and 3 years was 88.7%, 83.9%, and 55.9%
      in the CAHF group and 80.7%, 71.4%, and 57.1% in the LCAF group, respectively (p
      = 0.1251). The 1-, 2-, and 3-year survival rate was 79.6%, 51.6%, and 37.6% in
      the CAHF group and 80.0%, 57.6%, and 41.2% in the LCAF group, respectively (p =
      0.5757). Multivariate analysis showed that age and lesion length were independent
      significant prognostic factors for local control rate, and age was for the
      overall survival rate. The fractionation schedule had no significant prognostic
      effect. CONCLUSION: CAHF and LCAF result in similar 1-, 2-, and 3-year local
      control and survival rates. CAHF resulted in more severe acute esophagitis and
      may be less well tolerated than LCAF. The treatment results after the CAHF and
      LCAF regimens were better than those of historical conventional RT.

PMID- 12182983
TI  - Gemcitabine, paclitaxel, and radiation for locally advanced pancreatic cancer: a
      Phase I trial.
AB  - PURPOSE: To determine the maximum tolerated dose (MTD) and dose-limiting
      toxicities of gemcitabine, paclitaxel, and concurrent radiation for pancreatic
      cancer. METHODS AND MATERIALS: Twenty patients with locally unresectable
      pancreatic cancer were studied. The initial dose level was gemcitabine 75 mg/m(2)
      and paclitaxel 40 mg/m(2) weekly for 6 weeks. Concurrent radiation to 50.4 Gy was
      delivered in 1.8 Gy fractions. The radiation fields included the primary tumor,
      plus the regional peripancreatic, celiac, and porta hepatis lymph nodes. RESULTS:
      Dose-limiting toxicities of diarrhea, dehydration, nausea, and anorexia occurred
      in 3 of 3 patients at the second dose level of gemcitabine, 150 mg/m(2)/week. An
      intermediate dose level of gemcitabine, 110 mg/m(2)/week, was added, but
      gastrointestinal toxicity and pulmonary pneumonitis were encountered. The MTD
      therefore was gemcitabine 75 mg/m(2)/week with paclitaxel 40 mg/m(2)/week and
      concurrent radiation. Two of 11 patients treated at the MTD had Grade 3/4
      toxicity. Four of 10 assessable patients treated at the MTD responded (40%),
      including one pathologic complete response. CONCLUSION: The maximum tolerated
      dosage of gemcitabine is 75 mg/m(2)/week with paclitaxel 40 mg/m(2)/week and
      conventional 50.4 Gy radiation fields. A Phase II Radiation Therapy Oncology
      Group study is under way.

PMID- 12182984
TI  - Long-term control of T2-T3 rectal adenocarcinoma with radiotherapy alone.
AB  - PURPOSE: To analyze the long-term result of patients presenting with T2-T3 rectal
      adenocarcinoma treated with curative intent by radiotherapy (RT) alone, using a
      combination of contact RT, external beam RT, and brachytherapy with an iridium
      implant. Patients were considered unsuitable for surgery because of the presence
      of severe comorbidity or because they did not consent to surgery and the
      possibility of a permanent stoma. METHODS AND MATERIALS: Between 1986 and 1998,
      63 patients (56 staged with endorectal ultrasonography) were entered into a pilot
      study. Patients had to have T2-T3, N0-N1, M0 adenocarcinoma of the middle or
      lower rectum involving less than two-thirds of the circumference. RT began with
      contact X-rays (80 Gy in 3 fractions for 21 days), followed by external beam RT
      (39 Gy in 13 fractions for 17 days) with a concomitant boost (4 Gy in 4
      fractions). After a 4-6-week interval, an iridium implant delivered a completion
      dose of 20 Gy to the tumor. No chemotherapy was given. RESULTS: The median age of
      the patients was 72 years. Of the 63 patients, 41 had T2 and 22 had T3 tumors.
      The mean distance of the tumor from the anal verge was 3.6 cm. All patients
      completed treatment according to the protocol, except for 7 for whom
      brachytherapy was not performed. With a median follow-up time of 54 months, the
      primary local tumor control rate was 63%; after salvage surgery, the ultimate
      pelvic control was 73% (46 of 63). The 5-year overall survival rate was 64.4%,
      and for 42 patients aged <80 years, it was 78% with 10 patients alive and well at
      > or =10 years. No severe Grade 3-4 toxicity was seen. Acute proctitis was seen
      in most patients but did not require treatment interruption. Late rectal bleeding
      occurred in 24 patients. Only 1 required blood transfusion. Good anorectal
      function was maintained in 92% of living patients. The T stage was a strong
      prognostic factor, with a 5-year overall survival rate of 84% and 53% for T2 and
      T3 lesions, respectively, in patients <80 years old. CONCLUSION: This is the
      first report of long-term local control and survival for ultrasound-staged T2-T3
      rectal adenocarcinoma treated by RT alone, showing that high-dose irradiation to
      a small volume can provide a high therapeutic ratio for such tumors.

PMID- 12182985
TI  - Dose-response relationship in local radiotherapy for hepatocellular carcinoma.
AB  - PURPOSE: Dose escalation using three-dimensional conformal radiotherapy (3D-CRT)
      is based on the hypothesis that increasing the dose can enhance tumor control.
      This study aimed to determine whether a dose-response relationship exists in
      local radiotherapy for primary hepatocellular carcinoma (HCC). METHODS AND
      MATERIALS: One hundred fifty-eight patients were enrolled in the present study
      between January 1992 and March 2000. The exclusion criteria included the presence
      of an extrahepatic metastasis, liver cirrhosis of Child class C, tumors occupying
      more than two-thirds of the entire liver, and a performance status on the Eastern
      Cooperative Oncology Group scale of more than 3. Radiotherapy was given to the
      field, including the tumor, with generous margin using 6- or 10-MV X-rays. The
      mean radiation dose was 48.2 +/- 7.9 Gy in daily 1.8-Gy fractions. The tumor
      response was assessed based on diagnostic radiologic examinations, including a
      computed tomography scan, magnetic resonance imaging, and hepatic artery
      angiography 4-8 weeks after the completion of treatment. Liver toxicity and
      gastrointestinal complications were evaluated. RESULTS: An objective response was
      observed in 106 of 158 (67.1%) patients. Statistical analysis revealed that the
      total dose was the most significant factor associated with the tumor response.
      The response rates in patients treated with doses <40 Gy, 40-50 Gy, and >50 Gy
      were 29.2%, 68.6%, and 77.1%, respectively. Survivals at 1 and 2 years after
      radiotherapy were 41.8% and 19.9%, respectively, with a median survival time of
      10 months. The rate of liver toxicity according to the doses <40 Gy, 40-50 Gy,
      and >50 Gy was 4.2%, 5.9%, and 8.4%, respectively, and the rate of
      gastrointestinal complications was 4.2%, 9.9%, and 13.2%, respectively.
      CONCLUSIONS: The present study showed the existence of a dose-response
      relationship in local radiotherapy for primary HCC. Only the radiation dose was a
      significant factor for predicting an objective response. The results of this
      study showed that 3D-CRT can theoretically be used for treating primary HCC.

PMID- 12182986
TI  - Radiation-induced liver disease after three-dimensional conformal radiotherapy
      for patients with hepatocellular carcinoma: dosimetric analysis and implication.
AB  - PURPOSE: To analyze the correlation of radiation-induced liver disease (RILD)
      with patient-related and treatment-related dose-volume factors and to describe
      the probability of RILD by a normal tissue complication probability (NTCP) model
      for patients with hepatocellular carcinoma (HCC) treated with three-dimensional
      conformal radiotherapy (3D-CRT). METHODS AND MATERIALS: Between November 1993 and
      December 1999, 93 patients with intrahepatic malignancies were treated with 3D
      CRT at our institution. Sixty-eight patients who were diagnosed with HCC and had
      complete 3D dose-volume data were included in this study. Of the 68 patients, 50
      had chronic viral hepatitis before treatment, either type B or type C. According
      to the Child-Pugh classification for liver cirrhosis, 53 patients were in class A
      and 15 in class B. Fifty-two patients underwent transcatheter arterial
      chemoembolization with an interval of at least 1 month between transcatheter
      arterial chemoembolization and 3D-CRT to allow adequate recovery of hepatic
      function. The mean dose of radiation to the isocenter was 50.2 +/- 5.9 Gy, in
      daily fractions of 1.8-2Gy. No patient received whole liver irradiation. RILD was
      defined as Grade 3 or 4 hepatic toxicity according to the Common Toxicity
      Criteria of the National Cancer Institute. All patients were evaluated for RILD
      within 4 months of RT completion. Three-dimensional treatment planning with dose
      volume histogram analysis of the normal liver was used to compare the dosimetric
      difference between patients with and without RILD. Maximal likelihood analysis
      was conducted to obtain the best estimates of parameters of the Lyman NTCP model.
      Confidence intervals of the fitted parameters were estimated by the profile
      likelihood method. RESULTS: Twelve of the 68 patients developed RILD after 3D
      CRT. None of the patient-related variables were significantly associated with
      RILD. No difference was found in tumor volume (780 cm(3) vs. 737 cm(3), p =
      0.86), normal liver volume (1210 cm(3) vs. 1153 cm(3), p = 0.64), percentage of
      normal liver volume with radiation dose >30 Gy (V(30 Gy); 42% vs. 33%, p = 0.05),
      and percentage of normal liver volume with >50% of the isocenter dose (V(50%);
      45% vs. 36%, p = 0.06) between patients with and without RILD. The mean hepatic
      dose was significantly higher in patients with RILD (2504 cGy vs. 1965 cGy, p =
      0.02). The probability of RILD in patients could be expressed as follows:
      probability = 1/[1 + exp(-(0.12 x mean dose - 4.29))], with coefficients
      significantly different from 0. The best estimates of the parameters in the Lyman
      NTCP model were the volume effect parameter of 0.40, curve steepness parameter of
      0.26, and 50% tolerance dose for uniform irradiation of whole liver [TD(50)(1)]
      of 43 Gy. Patients with RILD had a significantly higher NTCP than did those with
      no RILD (26.2% vs. 15.8%; p = 0.006), using the best-estimated parameters.
      CONCLUSION: Dose-volume histogram analysis can be effectively used to quantify
      the tolerance of the liver to RT. Patients with RILD had received a significantly
      higher mean dose to the liver and a significantly higher NTCP. The fitted volume
      effect parameter of the Lyman NTCP model was close to that from the literature,
      but much lower in our patients with HCC and prevalent chronic viral hepatitis
      than that reported in other series with patients with normal liver function.
      Additional efforts should be made to test other models to describe the radiation
      tolerance of the liver for Asian patients with HCC and preexisting compromised
      hepatic reserve.

PMID- 12182988
TI  - Whole abdominopelvic radiotherapy for desmoplastic small round-cell tumor.
AB  - PURPOSE: Desmoplastic small round-cell tumor (DSRCT) is a rare, recently
      described intraperitoneal malignancy occurring predominantly in adolescent boys.
      Our objective was to evaluate the feasibility and outcome of whole abdominopelvic
      irradiation (WAPI) as part of a combined modality protocol for patients with
      DSRCT. METHODS AND MATERIALS: The records of all 21 patients treated with WAPI
      for DSRCT at our institution from 1992 to 2001 were retrospectively reviewed.
      Patients were treated on an institutional protocol with 7 cycles of an alkylator
      based chemotherapy. After maximal surgical debulking, patients were treated with
      external beam radiotherapy to the whole abdomen and pelvis to a dose of 30 Gy.
      RESULTS: All 21 patients completed the prescribed treatment. The median follow-up
      was 28 months. The overall survival and relapse-free survival rate at 3 years was
      48% and 19%, respectively. The median survival was 32 months, and the median time
      to relapse was 19 months. Most relapses were intraperitoneal and/or hepatic.
      Acute toxicities included Radiation Therapy Oncology Group Grade 2 upper and
      lower gastrointestinal toxicity in 81% and 71% of patients, respectively. All
      patients experienced acute hematologic toxicity, with Grade 4 thrombocytopenia,
      leukopenia, and anemia in 76%, 29%, and 33%, respectively. The major long-term
      toxicity was small bowel obstruction, which occurred in 7 patients (33%) after
      surgery and WAPI. CONCLUSION: DSRCT is a rare and highly lethal disease,
      requiring aggressive multimodality therapy. WAPI is feasible in conjunction with
      intensive chemotherapy and surgery. Hematologic and gastrointestinal toxicities
      are expected but manageable with diligent supportive care. The long-term efficacy
      of this therapy remains disappointing, thus novel approaches are being
      investigated.

PMID- 12182987
TI  - Outcome of primary soft tissue sarcoma of the knee and elbow.
AB  - PURPOSE: Concern is frequently raised regarding the tolerance of irradiation over
      a joint space. The purpose of this study was to determine the outcome in terms of
      relapse and potential complications in patients with knee and elbow soft tissue
      sarcoma treated with limb-sparing surgery with or without adjuvant radiotherapy
      (RT). METHODS AND MATERIALS: A review of our prospective database between June
      1982 and December 1999 identified 86 adult patients with primary soft tissue
      sarcoma arising from the knee (n = 65; 76%) or elbow (n = 21; 24%) treated with
      limb-sparing surgery. Tumors had high-grade histologic features in 72% and were
      >5 cm in 48% of patients. Adjuvant RT was given to 46 (54%) of 86 patients. The
      type of RT was postoperative external beam RT in 63% and brachytherapy in 37%. Of
      the 46 patients who received RT, 85% (n = 39) had deep, 78% (n = 36) high-grade,
      and 54% (n = 25) >5-cm tumors. Complications were assessed in terms of wound
      complications requiring repeated surgery, bone fracture, nerve damage, and joint
      stiffness. RESULTS: With a median follow-up of 48 months (range 4-175), the 5
      year actuarial rate of local control, distant control, and overall survival was
      75% (95% confidence interval [CI] 64-85%), 82% (95% CI 73-91%), and 81% (95% CI
      71-91%), respectively. The 5-year local control rate for patients who received RT
      was 80% vs. 71% for those who did not (p = 0.3). The type of RT did not
      significantly influence the local control rate. Patients treated with external
      beam RT had a 5-year local control rate of 84% compared with 73% for those
      treated with brachytherapy (p = 0.4). On multivariate analysis, tumor size >5 cm
      retained its significance as an independent predictor of poor local control (p =
      0.04; relative risk 3; 95% CI 1-6). In addition, high-grade histologic features
      emerged as an independent predictor of local recurrence (p = 0.02; relative risk
      4; 95% CI 1-20). No statistically significant difference was found between the RT
      and no-RT group in terms of the 5-year actuarial rate of wound reoperation (10%
      vs. 3%, p = 0.1), bone fracture (3% vs. 5%, p = 0.5), or nerve damage (6% vs. 3%,
      p = 0.5). Joint stiffness was significantly higher in the RT group (24% vs. 0%, p
      = 0.001), but this stiffness was severe to moderate in only 2 patients.
      CONCLUSION: On the basis of the findings of this retrospective review, adjuvant
      RT seems to be relatively well tolerated despite the inclusion of part of the
      joint space in the irradiation portal. Joint stiffness was seen more frequently
      with adjuvant RT, but it was moderate to severe in only a small number of
      patients.

PMID- 12182989
TI  - External beam radiotherapy for primary and adjuvant management of aggressive
      fibromatosis.
AB  - PURPOSE: To review a large single-institution experience in the management of
      aggressive fibromatosis to determine the effectiveness of external beam
      radiotherapy (EBRT) and identify the presentation and treatment variables
      predictive of locoregional control. METHODS AND MATERIALS: Between 1975 and 2000,
      72 patients were treated with EBRT for a pathologically confirmed diagnosis of
      aggressive fibromatosis. Thirty patients were treated at the primary presentation
      and 42 at the time of a locoregional recurrence. Minimal 2-year follow-up data
      were available for 65 patients (median 6 years). Megavoltage irradiation with
      60Co to 20 MV photons or electron therapy was used for all patients. Most
      patients were treated after attempted complete surgical resection; 16 patients
      underwent pretreatment biopsy alone. The prescribed treatment was standard (1.8
      Gy) daily fractions in 42 cases and 1.2 Gy fractions b.i.d. in 23 cases. The
      median prescribed dose was 54 Gy. The prognostic variables and treatment results
      were evaluated by Kaplan-Meier actuarial analysis. RESULTS: Locoregional control
      was achieved in 52 of 65 patients. The 5-year actuarial locoregional control was
      83%. Locoregional failure occurred in 13 patients (11 in patients with recurrent
      tumors). Only two failures occurred within the irradiation fields; nine failures
      occurred at the field margins. Eleven patients were salvaged by surgery: wide
      excision in nine and amputation in two. The only prognostic factor significant
      for locoregional control was primary vs. recurrent presentation (p = 0.0193). The
      5-year locoregional control rates for irradiation at initial presentation and at
      recurrence were 96% and 75%, respectively. The variables without significance for
      locoregional control included primary tumor location, surgical procedures
      performed, resection margins, and gross vs. microscopic residual tumor at
      irradiation. Lymphedema was the most common late effect, occurring in 7 patients,
      5 with prior treatment. Bone fracture occurred in 3 patients; all 3 had
      fibromatosis involving the bone at presentation but without recurrence at the
      time of fracture. CONCLUSION: EBRT is effective treatment for aggressive
      fibromatosis. The probability of locoregional control decreases with multiple
      prior recurrences.

PMID- 12182990
TI  - Early stage nasal NK/T-cell lymphoma: clinical outcome, prognostic factors, and
      the effect of treatment modality.
AB  - PURPOSE: To determine the clinical outcome, prognostic factors, and effect of
      adding combination chemotherapy to radiation therapy on disease control and
      survival in early stage nasal natural killer (NK)/T-cell lymphoma. METHODS AND
      MATERIALS: A retrospective "intent to treat" analysis was carried out on 79
      patients treated consecutively with curative intent between 1977 and June 2001.
      They all had early stage (Ann Arbor Stage I(E): 63, II(E):16) nasal NK/T-cell
      lymphoma. Sixty-one were planned for combined modality treatment (CMT);
      radiotherapy alone (RT) was intended for 18. Three to 6 cycles of anthracycline
      containing regimens were aimed at for patients intended for CMT. Patients
      selected for RT were generally older or treated during the earlier part of the
      study period. RESULTS: The overall complete response (CR) rate was 68.4% (54/79),
      of whom 44.4% (24/54) relapsed after 54.9 months median follow-up of the
      survivors. The 5-year disease-free survival (DFS) and overall survival (OS) rates
      were 35.5% and 37.9%, respectively. On multivariate analysis, good performance
      status (Eastern Cooperative Oncology Group [ECOG] <2) was shown to be a
      significant favorable factor for DFS (p = 0.011), whereas good performance status
      (ECOG <2) and Ann Arbor Stage I(E) disease were shown to be significant favorable
      factors for OS (p = 0.001 and p = 0.013, respectively). The type of intended
      treatment was not a significant factor for DFS (5-year DFS CMT vs. RT = 35.8% vs.
      30.5%, p = 0.795) or OS (5-year OS CMT vs. RT = 40.3% vs. 29.8%, p = 0.693)
      though only 2 of the 16 Stage II(E) patients were intended for RT alone.
      Resistance to treatment, especially to chemotherapy, was common. Of 61 patients
      intended to be given CMT, 31 showed disease progression while receiving
      chemotherapy, of whom 17 progressed locoregionally. Nine of the latter group were
      rendered CR by salvage radiotherapy. CONCLUSIONS: The overall outcome in early
      stage nasal NK/T-cell lymphoma is poor. Performance status and Ann Arbor stage
      are significant factors influencing DFS and OS. The addition of anthracycline
      containing chemotherapy to radiotherapy does not appear to confer any survival
      benefit in Stage I(E) patients. Therefore, radiation therapy remains the mainstay
      of treatment for this lymphoma type.

PMID- 12182991
TI  - Phase III study of ibuprofen versus placebo for radiation-induced genitourinary
      side effects.
AB  - PURPOSE: On the basis of our anecdotal clinical observations that nonsteroidal
      anti-inflammatory agents relieved dysuria during radiotherapy for patients with
      prostate cancer, we conducted a Phase III randomized trial of ibuprofen vs.
      placebo for patients who had an increase in acute urinary symptoms. Our in vitro
      and in vivo laboratory data with a higher concentration of ibuprofen than
      achievable in this study demonstrated radiosensitization. This study examined
      whether the inflammatory response within the prostate during radiotherapy would
      respond to the standard dose of ibuprofen as assessed by a symptom score. METHODS
      AND MATERIALS: Patients were registered to the study and were followed weekly
      with a formal symptom assessment. A double-blind randomization to ibuprofen, 400
      mg q.i.d., vs. placebo for 7 days was done at a time when the severity score
      increased. The symptom response was evaluated at the end of the week. RESULTS:
      Between 1995 and 1998, 100 patients were entered, 28 did not have a sufficient
      change in symptom score to be randomized, and 19 were either unable to take
      ibuprofen or withdrew before randomization. Of the 53 patients randomized, 27
      received placebo and 26 ibuprofen. No statistically significant differences were
      found between the placebo and ibuprofen groups between baseline and randomization
      or between randomization and the 1-week posttreatment assessment. Neither group
      had a change in symptom severity between randomization and the 1-week
      posttreatment evaluation. CONCLUSION: The standard anti-inflammatory dose of
      ibuprofen did not relieve the acute urinary or rectal symptoms during
      radiotherapy for prostate cancer. The nonsteroidal anti-inflammatory drugs are
      potential radiation sensitizers with the mechanism of action as yet unknown.
      Clinical trials of the cyclooxygenase inhibitors as radiation sensitizers should
      explore a range of doses and evaluate potential mechanisms of action, including
      cyclooxygenase inhibition and other non-cyclooxygenase mechanisms.

PMID- 12182992
TI  - The efficacy of octreotide in the therapy of acute radiation-induced diarrhea: a
      randomized controlled study.
AB  - PURPOSE: Although the somatostatin analog octreotide is currently used in the
      treatment of chemotherapy-induced diarrhea and secretory diarrhea associated with
      various disorders, its role in the management of radiation enteritis is not well
      defined. We performed a randomized study that compared octreotide acetate with
      diphenoxylate hydrochloride plus atropine sulfate, the drug commonly used as
      therapy for acute radiation-induced diarrhea (ARID). METHODS AND MATERIALS: Sixty
      one patients with Grade 2 (four to six stools per day) or Grade 3 (> or = seven
      stools per day, National Cancer Institute Common Toxicity Criteria) diarrhea
      associated with pelvic radiotherapy were assigned randomly to receive octreotide
      s.c., 100 microg three times daily (n = 33) or diphenoxylate and atropine orally,
      2.5 mg four times daily (n = 28). Radiotherapy was delivered to all patients in a
      conventional manner, with high-energy photons in a total dose > or =45 Gy, which
      exceeds the tolerance of intestine. Overall, there was no significant difference
      in patient characteristics or radiotherapy applied between the two arms. Patients
      were evaluated daily for the primary study end point, resolution of diarrhea, as
      well as for interruption of pelvic radiotherapy. RESULTS: Within 3 days, ARID
      completely resolved in 20 patients in the octreotide arm (2 within the first day,
      11 within the second day, and 7 within the third day) vs. only 4 (all within the
      second day of therapy) in the diphenoxylate arm (p = 0.002). On the diphenoxylate
      arm, 15/28 patients were required to discontinue pelvic radiotherapy; on the
      octreotide arm, 6/33 patients were required to discontinue pelvic radiotherapy
      for an average of 1.89 +/- 0.5 and 0.45 +/- 0.2 days, respectively (p = 0.003).
      No side effects were observed in either arm. Three patients on the diphenoxylate
      arm and only 1 on the octreotide arm required further treatment for parenteral
      replenishment of fluids and electrolytes or other antidiarrheal treatments.
      CONCLUSION: Octreotide seems to be more effective than conventional therapy with
      diphenoxylate and atropine in controlling ARID and eliminating the need for
      radiotherapy interruptions.

PMID- 12182994
TI  - Prevalence of symptom control and palliative care abstracts presented at the
      Annual Meeting of the American Society for Therapeutic Radiology and Oncology.
AB  - PURPOSE: Forty percent of all patients referred for radiotherapy are treated with
      palliative intent. The American Society for Therapeutic Radiology and Oncology
      (ASTRO) has recently emphasized the importance of radiation oncologists being
      skilled in the field of symptom control and palliative care (SCPC). The purpose
      of this study was to determine the number of abstracts relating to SCPC presented
      at the annual ASTRO meetings. METHODS AND MATERIALS: The number of SCPC abstracts
      presented at ASTRO meetings between 1993 and 2000 was counted. Abstracts were
      included if they described populations with advanced or metastatic cancer for
      whom the goal of treatment was symptom palliation. The treatment sites and
      symptoms palliated were recorded. RESULTS: Of 3511 abstracts presented at ASTRO
      between 1993 and 2000, an average of 47 (1.3%, range 0.9-2.2%/y) were related to
      SCPC. The most common treatment sites were bone, brain, and lung. Pain, bleeding,
      and neurologic and pulmonary symptoms were the ones most commonly palliated.
      Thirty-two percent of the SCPC abstracts involved randomized controlled trials,
      47% had palliation of symptoms as a secondary treatment outcome, and in 21%, the
      symptomatic treatment outcome was not specifically stated. CONCLUSION: SCPC
      research has been poorly represented at the annual ASTRO meetings. Education and
      research in this field needs to be actively encouraged, because SCPC is an
      important component of a radiation oncologist's role in comprehensive patient
      care.

PMID- 12182993
TI  - Long-term alterations of oral mucosa in radiotherapy patients.
AB  - PURPOSE: The aim of this investigation was to describe the alterations in oral
      mucosa after radiotherapy. METHODS AND MATERIALS: Biopsies were taken from
      patients before irradiation, at 60 Gy, and 6-12 months after radiotherapy.
      Histomorphological evaluation of the vessels was performed, and endothelial
      expression of ICAM-1, VCAM-1, and E-selectin was also evaluated, as well as
      distribution of LFA-1-, Mac-1-, VLA-4-, RM3/1-, 27E10-, and 25F9-bearing cells in
      the subepithelial tissue. RESULTS: The expression of ICAM-1 was downregulated
      after radiotherapy, whereas the percentage of LFA-1- and VLA-4-bearing cells
      increased. VCAM-1 remained at low levels. The subepithelial infiltration was
      still dominated by RM3/1-positive macrophages. The number of vessels decreased,
      while the lumina of the remaining vessels in the deeper connective layer
      increased. CONCLUSIONS: The late effects of radiotherapy are characterized by a
      decreased number of blood vessels and by significantly different expression
      patterns of the adhesion molecules studied, and of integrins and macrophage
      subpopulations compared to the conditions before irradiation and at 60 Gy.

PMID- 12182996
TI  - How fast is repopulation of tumor cells during the treatment gap?
AB  - PURPOSE/OBJECTIVE: Our goal was to analyze the repopulation of surviving tumor
      cells during a treatment gap in radiotherapy for head-and-neck cancer. METHODS
      AND MATERIALS: Clinical material is based on the records of 1502 patients treated
      by radiotherapy alone in Maria Sklodowska-Curie Memorial Institute in Gliwice
      during the period between1980 and 1989. All patients had histologically confirmed
      squamous cell carcinoma of the larynx or pharynx. The mean gap duration was 9
      days. Only 10% of patients were treated without gaps. The dose per fraction was
      in the range of 1.5 to 2.5 Gy. Patient data were fitted directly to the mixed
      linear-quadratic model using maximum-likelihood estimation. Tumor stage or tumor
      localization was introduced into the equation as a categorical variable. Tumor
      proliferation was estimated by dividing the treatment gaps into three groups: the
      first 2 weeks, second 2 weeks, and the period after 4 weeks of irradiation.
      RESULTS: Tumor control probability was significantly correlated with radiation
      dose, tumor progression (according to TNM), overall treatment time, and gap
      duration. Laryngeal cancers had a better prognosis than cancers of the oro- and
      nasopharynx. Significant tumor repopulation was found after the first 2 weeks of
      radiotherapy. During the treatment gap, the proliferation rate was equal to 0.75
      Gy/day. During the days with irradiation, repopulation was slower and equal to
      0.2 Gy/day. CONCLUSION: The repopulation of tumor cells is faster during a gap
      than during the normal days of irradiation. Accelerated repopulation probably
      starts soon after 2 weeks of irradiation.

PMID- 12182995
TI  - Vascular architecture, hypoxia, and proliferation in first-generation xenografts
      of human head-and-neck squamous cell carcinomas.
AB  - PURPOSE: To quantify the physiologic status of human tumor cells in relation to
      the tumor vasculature. METHODS AND MATERIALS: Fourteen tumors of 11 first
      generation xenograft lines of human head-and-neck squamous cell carcinoma were
      injected with the hypoxic cell marker pimonidazole, the proliferation marker
      BrdUrd, and the perfusion marker Hoechst 33342. Consecutive tissue sections were
      processed with immunohistochemical methods and analyzed with image-analysis
      techniques. RESULTS: Three different hypoxic patterns were found: patchy, ribbon
      like, and mixed. An image-analysis method was developed to quantify these, and an
      elongation index (length/width) was calculated for hypoxia. The mean elongation
      indices ranged from 2.0 to 28.3 and showed a good correlation with the visual
      scoring of hypoxic patterns. Comparative analysis of hypoxic and proliferating
      cells in zones around the tumor vasculature showed the presence of both hypoxic
      and proliferating cells in all zones up to 250 microm from the vessels. The
      largest coexistence of hypoxic and proliferating cells seemed to occur at 50-100
      microm from the vessels. CONCLUSIONS: The three hypoxic patterns could be
      quantified by an elongation index, which is an additional parameter that allows
      distinction of tumors with similar fractions of hypoxic cells. The analysis of
      hypoxic and proliferating cells as a function of distance from the tumor
      vasculature indicates that proliferation does occur also at low oxygen tensions.

PMID- 12182997
TI  - Sensitivity to ionizing radiation and chemotherapeutic agents in gemcitabine
      resistant human tumor cell lines.
AB  - PURPOSE: To determine cross-resistance to anti-tumor treatments in
      2',2'difluorodeoxycytidine (dFdC, gemcitabine)-resistant human tumor cells.
      METHODS AND MATERIALS: Human lung carcinoma cells SW-1573 (SWp) were made
      resistant to dFdC (SWg). Sensitivity to cisplatin (cDDP), paclitaxel, 5
      fluorouracil (5-FU), methotrexate (MTX), cytarabine (ara-C), and dFdC was
      measured by a proliferation assay. Radiosensitivity and radioenhancement by dFdC
      of this cell panel and the human ovarian carcinoma cell line A2780 and its dFdC
      resistant variant AG6000 were determined by clonogenic assay. Bivariate
      flowcytometry was performed to study cell cycle changes. RESULTS: In the SWg, a
      complete deoxycytidine kinase (dCK) deficiency was found on mRNA and protein
      level. This was accompanied by a 10-fold decrease in dCK activity which resulted
      in the >1000-fold resistance to dFdC. Sensitivity to other anti-tumor drugs was
      not altered, except for ara-C (>100-fold resistance). Radiosensitivity was not
      altered in the dFdC-resistant cell lines SWg and AG6000. High concentrations (50
      100 microM dFdC) induced radioenhancement in the dFdC-resistant cell lines
      similar to the radioenhancement obtained at lower concentrations (10 nM dFdC) in
      the parental lines. An early S-phase arrest was found in all cell lines after
      dFdC treatment where radioenhancement was achieved. CONCLUSIONS: In the dFdC
      resistant lung tumor cell line SWg, the deficiency in dCK is related to the
      resistance to dFdC and ara-C. No cross-resistance was observed to other anti
      tumor drugs used for the treatment in lung cancer. Sensitivity to ionizing
      radiation was not altered in two different dFdC-resistant cell lines. Resistance
      to dFdC does not eliminate the ability of dFdC to sensitize cells to radiation.

PMID- 12182998
TI  - Amelioration of acute oral mucositis by keratinocyte growth factor: fractionated
      irradiation.
AB  - PURPOSE: The aim of the present study was to quantify the protective efficacy of
      recombinant human keratinocyte growth factor (rHuKGF) in oral mucosa. METHODS AND
      MATERIALS: Mouse tongue mucosal ulceration was analyzed as the clinically
      relevant end point. Fractionated irradiation of the snout with 5 daily fractions
      of 3 Gy was followed by graded test doses, given to a test area of the lower
      tongue, on Day 7. rHuKGF was injected s.c. in daily doses of 5 mg/kg before
      radiotherapy, during radiotherapy, over the weekend break, or a combination.
      Moreover, single rHuKGF injections (5 or 15 mg/kg) were given on Day -1 or on Day
      4. RESULTS: In a single-dose control experiment, the ED50, i.e., the dose after
      which ulcer induction is expected in 50% of the mice, was 10.9 +/- 0.7 Gy.
      Fractionated irradiation without keratinocyte growth factor rendered an ED50 for
      test irradiation of 5.6 +/- 3.7 Gy. Keratinocyte growth factor increased the ED50
      values to 7.8 +/- 3.3 Gy (Days -3 to -1, p = 0.01), 8.3 +/- 1.6 Gy (Days -4 to 
      2, p = 0.0008), 10.5 +/- 1.4 Gy (Days 0 to +2, p = 0.0002), 11.0 +/- 0.5 Gy (Days
      0 to +4, p = 0.002), 10.6 +/- 1.4 Gy (Days +4 to +6, p = 0.0021), 10 +/- 0.07
      (Days -3 to +1, p = 0.0001) or 11.0 +/- 0.02 (Days +4 to +8, p = 0.0001). This is
      equivalent to compensation of approximately 1.5 fractions of 3 Gy when rHuKGF is
      given before radiotherapy and 3-4 fractions in all other protocols by rHuKGF
      treatment. Single rHuKGF injections were similarly (5 mg/kg) or more (15 mg/kg)
      effective. CONCLUSIONS: In conclusion, these results indicate a marked increase
      in oral mucosal radiation tolerance by rHuKGF, which is most pronounced if the
      growth factor is applied during fractionated radiotherapy. The effect seems to be
      based on complex mechanisms, predominantly changes in both epithelial
      proliferation and differentiation processes.

PMID- 12182999
TI  - Effectiveness of radioactive tungsten source in the prevention of restenosis in
      stented porcine coronary arteries.
AB  - PURPOSE: Intracoronary radiation has shown the potential to inhibit neointimal
      proliferation in porcine models of restenosis. The objective of this study was to
      determine whether intracoronary radiation using a new coiled wire of tungsten-188
      ((188)W), a pure beta emitter (half-life 69.4 days) is safe. In addition, a dose
      of 0 Gy, 18 Gy, or 25 Gy prescribed to 2 mm from the center of the source and
      delivered intraluminally is sufficient to prevent restenosis and free from
      adverse effects. METHODS AND MATERIALS: Ten domestic swine underwent 13-mm stent
      implantation (SI) into two arteries, left anterior descending plus either the
      left circumflex or right coronary artery. After SI, a closed-end lumen radiation
      catheter was inserted to the treated artery and a 40-mm coiled (188)W source was
      manually delivered to cover the stented segment and its margins. A total of 20
      arteries were randomized to treatment with a radiation dose of 0, 18 Gy, or 25 Gy
      delivered to 2 mm depth from the center of the source. Four weeks after the
      procedure, the swine underwent angiography and intravascular ultrasound using
      automated pullback at 0.5 mm/s. before being killed and the arteries perfusion
      fixed. Histopathologic and histomorphometric analyses were performed at 28 days
      after injury and radiation. RESULTS: Irradiation with (188)W at a dose of 25 Gy
      after SI significantly inhibited neointima formation (intimal area: 1.05 +/- 0.64
      vs. 2.75 +/- 0.99 mm(2), p < 0.01) and at an 18 Gy dose of radiation (intimal
      area: 1.73 +/- 0.49 vs. 2.75 +/- 0.99 mm(2)), as compared to controls. One artery
      receiving 18 Gy and two arteries receiving 25 Gy were totally occluded at follow
      up due to thrombus formation but no edge stenosis was observed in any of the
      irradiated arteries. CONCLUSIONS: Intracoronary radiation therapy using a new
      coiled wire of (188)W source delivered after SI appeared to be safe and well
      tolerated. The radiation doses demonstrated efficacy in reducing neointima
      formation in the porcine coronary stent injury model.

PMID- 12183000
TI  - External beam radiation attenuates venous neointimal hyperplasia in a pig model
      of arteriovenous polytetrafluoroethylene (PTFE) graft stenosis.
AB  - PURPOSE: Hemodialysis vascular access dysfunction is an enormous clinical problem
      that causes great morbidity and costs well over one billion dollars per annum.
      The vast majority of hemodialysis vascular access dysfunction occurs as a result
      of venous stenosis and thrombosis at the graft-vein anastomosis. At a cellular
      level, this venous stenosis is the result of venous neointimal hyperplasia (VNH).
      There are, unfortunately, no effective therapies for VNH. The purpose of this
      study was to assess the role of external radiation therapy in preventing VNH and
      venous stenosis. METHODS AND MATERIALS: Seven-centimeter polytetrafluoroethylene
      loop grafts were placed bilaterally between the femoral artery and vein of 12
      Yorkshire Cross pigs. One side was treated with a single 16-Gy dose of external
      beam radiation with a linear accelerator, while the contralateral side served as
      an internal control. Swine were killed after 28 days, and the grafts were
      carefully dissected out and removed. Neointimal hyperplasia and luminal stenosis
      were then assessed morphometrically at the graft-vessel anastomoses. RESULTS:
      External beam radiation therapy significantly reduced the amount of luminal
      stenosis at the graft-vein anastomosis, with minimal local and systemic toxicity.
      CONCLUSIONS: External beam radiation therapy could be a useful and clinically
      relevant local treatment for venous stenosis in polytetrafluoroethylene dialysis
      grafts.

PMID- 12183001
TI  - Thresholds for human detection of patient setup errors in digitally reconstructed
      portal images of prostate fields.
AB  - PURPOSE: Computer-assisted methods to analyze electronic portal images for the
      presence of treatment setup errors should be studied in controlled experiments
      before use in the clinical setting. Validation experiments using images that
      contain known errors usually report the smallest errors that can be detected by
      the image analysis algorithm. This paper offers human error-detection thresholds
      as one benchmark for evaluating the smallest errors detected by algorithms.
      Unfortunately, reliable data are lacking describing human performance. The most
      rigorous benchmarks for human performance are obtained under conditions that
      favor error detection. To establish such benchmarks, controlled observer studies
      were carried out to determine the thresholds of detectability for in-plane and
      out-of-plane translation and rotation setup errors introduced into digitally
      reconstructed portal radiographs (DRPRs) of prostate fields. METHODS AND
      MATERIALS: Seventeen observers comprising radiation oncologists, radiation
      oncology residents, physicists, and therapy students participated in a two
      alternative forced choice experiment involving 378 DRPRs computed using the
      National Library of Medicine Visible Human data sets. An observer viewed three
      images at a time displayed on adjacent computer monitors. Each image triplet
      included a reference digitally reconstructed radiograph displayed on the central
      monitor and two DRPRs displayed on the flanking monitors. One DRPR was error
      free. The other DRPR contained a known in-plane or out-of-plane error in the
      placement of the treatment field over a target region in the pelvis. The range
      for each type of error was determined from pilot observer studies based on a
      Probit model for error detection. The smallest errors approached the limit of
      human visual capability. The observer was told what kind of error was introduced,
      and was asked to choose the DRPR that contained the error. Observer decisions
      were recorded and analyzed using repeated-measures analysis of variance. RESULTS:
      The thresholds of detectability averaged over all observers were approximately
      2.5 mm for in-plane translations, 1.6 degrees for in-plane rotations, 1 degrees
      for out-of-plane rotations, and 8% change in magnification for out-of-plane
      translations along the central axis. When one inexperienced observer is excluded,
      the average threshold for change in magnification is 5%. Experienced observers
      tended to perform better, but differences between groups were not statistically
      significant. Thresholds were computed as averages over all observers. Because of
      the broad range of observer capabilities, some detection tasks were too difficult
      for some observers, leading to missing threshold values in our data analysis. The
      missing values were excluded from computation of the average thresholds reported
      above. The effect of the missing values is to bias the average values toward the
      best human performance. CONCLUSIONS: Under favorable conditions, humans can
      detect small errors in setup geometry. The thresholds for error detection
      reported in this study are believed to represent rigorous but reasonable
      benchmarks that can be incorporated into studies evaluating algorithms for
      computer-assisted detection of setup errors in electronic portal images.

PMID- 12183002
TI  - IMRT of large fields: whole-abdomen irradiation.
AB  - PURPOSE: To assess the feasibility of inverse planning for whole-abdomen
      intensity-modulated radiation therapy (IMRT) with bone marrow and kidney sparing
      and to develop approaches to circumventing field size restrictions in the
      application of whole-abdomen IMRT using dynamic multileaf collimators (DMLC).
      METHODS AND MATERIALS: The entire peritoneal cavity as derived from serial
      computerized tomography scans was defined as the gross target volume, whereas the
      planning target volume (PTV) was defined as the gross target volume plus a 5-mm
      margin extending 1 cm superiorly and inferiorly. In 10 randomly selected
      patients, the PTV ranged from 5629 to 12578 cc (median 7935 cc), and the superior
      inferior, lateral, and anterior-posterior dimensions of the PTV ranged from 37 to
      46 cm (median 42.5 cm), 27 to 33 cm (median 29 cm), and 18 to 23 cm (median 20
      cm), respectively. A single isocenter was defined for patients with field length
      <40 cm. For patients with fields >40 cm, two isocenters were defined: one in the
      abdominal region, and the other in the pelvis. For IMRT planning, five 15-MV
      intensity-modulated beams at gantry angles of 180 degrees, 105 degrees, 35
      degrees, 325 degrees, and 255 degrees were used. Optimization was designed to
      spare kidneys and bones. To fully account for the significant scattered dose
      contributions, an iterative process for dose calculations was implemented in the
      optimization. To overcome the 15-cm field width limit of our DMLC delivery
      system, fields with a width >15 cm were split into two or more subfields. To
      minimize field match errors, adjacent subfields overlapped by at least 2 cm, with
      intensity "feathering" in the overlap region. For patients with two isocenters,
      fields were overlapped and feathered in the cephalad-caudad direction by at least
      3 cm. For comparison, conventional anterior-posterior/posterior-anterior 6-MV
      photon beams with posterior kidney blocks at extended distance were also
      generated for each patient. RESULTS: Treatment plan optimization calculations
      required 20-80 min on a 500-MHz DEC alpha workstation. Including beam splitting,
      an average of 16 DMLC beams was used per patient. Delivery of 150 cGy required,
      on average, 1442 monitor units. For the same dose constraints on the kidneys,
      whole-abdomen IMRT resulted in significant dose reduction to the bones and
      improved PTV coverage as compared to conventional treatment. For a prescription
      dose of 30 Gy, the volume of the pelvic bones receiving more than 21 Gy was
      reduced on average by almost 60% with IMRT, and the mean dose to all bones was
      reduced from 24.0 +/- 1.5 Gy to 18.5 +/- 1.0 Gy (p = 0.002). PTV coverage, as
      measured by V95 (the volume receiving 95% of the prescription dose), improved
      from 71.7 +/- 4.8% with conventional treatment to 83.5 +/- 3.9% with IMRT (p =
      0.002), although small regions of underdose in areas near the kidneys could not
      be avoided completely. The high-dose regions within the PTV, as measured by D05
      (the dose covering 5% of PTV volume), increased slightly from 31.2 +/- 0.6 Gy
      with conventional treatment to 32.8 +/- 0.2 Gy with IMRT. CONCLUSION: We have
      developed a process to plan and deliver whole-abdomen IMRT using standard linear
      accelerators and DMLC. IMRT can achieve better PTV coverage with the same level
      of kidney sparing and improved sparing of the bone marrow. These methods may be
      applicable also to other sites requiring large-field irradiation.

PMID- 12183003
TI  - Reducing the weight of the EC-L cassette.
AB  - PURPOSE: To model the EC-L portal film cassette to understand how its weight
      could be reduced without compromising image quality. METHODS AND MATERIALS: The
      BEAM99 Monte Carlo code was used to simulate a 6-MV X-ray beam impinging on a
      water phantom 15 or 40 cm thick and subsequently reaching image receptors of
      different designs. The image receptor model included the front cassette wall,
      lead or copper plates 0-1.2 g/cm(2) in thickness, a Lanex Fast screen pair, and
      the rear cassette wall. The signal generated in the phosphor screen from primary
      and scattered photons and charged particles was calculated for all image
      receptors and for both a water phantom and a water phantom plus bone object.
      Subject contract was calculated using the formalism of Motz and Danos, and the
      detective quantum efficiency was calculated using the formalism of Swank.
      Experimental cassettes with copper plate thicknesses of 0.5, 0.25, and 0.0 mm
      were used to image patients at several anatomic sites. RESULTS: Multiple scatter,
      especially at large field sizes, generates a low-energy X-ray component that can
      overrespond in the image receptor. The lead plate is more effective in reducing
      this X-ray scatter component than the copper plate. Filtering of the X-ray beam
      by the patient hardens the X-ray spectrum of a 6-MV X-ray beam, reducing subject
      contrast for thick patients. The front wall of the cassette plays an important
      role in contributing to the signals generated in the image receptor when the
      thickness of the metal plate is reduced. Over a wide variety of field sizes and
      patient thicknesses, subject contrast and detective quantum efficiency are
      relatively independent of metal plate thickness. CONCLUSIONS: The results suggest
      that a redesign of the EC-L cassette where the front wall of the cassette becomes
      part of the image receptor, and where the metal plate is changed to lead and the
      thickness reduced to 0.2 g/cm(2), would generate images of quality comparable to
      those of the existing EC-L cassette when used with a 6-MV X-ray beam. This change
      would reduce the weight of the EC-L cassette by 1040 g.

PMID- 12183004
TI  - In regard to Staar et al.: Intensified hyperfractionated accelerated radiotherapy
      limits the additional benefits of simultaneous chemotherapy-results of a
      multicentric randomized German trial in advanced head-and-neck cancer. IJROBP
      2001;50:1161-1171.

PMID- 12183005
TI  - 4-mm gamma knife helmet factor.

PMID- 12183007
TI  - Is ipsilateral radiation for tonsil cancer with limited tongue extension or T2N1
      tonsil cancer without tongue involvement appropriate?

PMID- 12183009
TI  - The SSRIs drug Fluoxetine, but not the noradrenergic tricyclic drug Desipramine,
      improves memory performance during acute major depression.
AB  - Accumulating evidence suggests that noradrenergic and serotonergic drugs are
      equally effective in ameliorating the depressive symptoms of major depression.
      Major depression is associated also with memory impairments, but the comparative
      effects of the antidepressant drugs on memory are not clear. We previously found
      that serotonergic neurotransmission is of particular importance for some aspects
      of episodic memory. We set out to test whether treatment with the selective
      serotonergic drug Fluoxetine (Prozac) would be advantageous in this respect over
      treatment with the selective noradrenergic tricyclic antidepressant drug
      Desipramine (Deprexan). Seventeen patients with major depressive episode,
      randomly assigned for treatment with either Fluoxetine (n = 8) or Desipramine (n
      = 9), were assessed for their clinical situation and for memory performance at
      the beginning of treatment, after 3 weeks, and after 6 weeks of pharmacological
      treatment. We found that although clinically both drugs were equally effective,
      the improvement of memory performance in the Fluoxetine-treated patients was
      significantly greater compared with that of the Desipramine-treated patients. The
      results support the role of serotonin in memory. More studies in larger samples
      of patients are required, but it may be that in cases where memory impairment is
      a major symptom, it would be beneficial to consider serotonergic antidepressant
      drugs for treatment. Furthermore, in cases where, for various reasons, the
      treatment of choice is noradrenergic, it may be worthwhile to consider a
      supplementary serotonergic drug to improve memory deficits.

PMID- 12183010
TI  - Effect of phenylephrine injected into the nucleus tractus solitarius of Sprague
      Dawley rats and spontaneously hypertensive rats.
AB  - In alpha-chloralose-anesthetized Sprague-Dawley (SD) rats with unilateral nucleus
      tractus solitarius (NTS) lesions, injection of the alpha(1)-adrenergic receptor
      agonist phenylephrine into the contralateral NTS dose-dependently increased
      arterial pressure (AP). Bunazosin (0.1 nmol) or prazosin (0.36 nmol), an alpha(1)
      adrenergic receptor antagonist, also increased AP. When injected into the NTS,
      pre-treatment with phenylephrine (10 nmol) or both antagonists abolished the
      cardiovascular effects of glutamate and acetylcholine. In contrast, pre-treatment
      with prazosin or methylatropine did not alter the effect of phenylephrine.
      Phenylephrine (30 nmol) injected into the NTS abolished aortic depressor nerve
      (ADN) evoked-responses. The pressor effect of phenylephrine in the NTS was
      exaggerated in spontaneously hypertensive rats (SHR). These results suggest that
      when injected into the NTS, the effect of phenylephrine may be due to a
      baroreflex blockade resulting from direct modulatory actions or non-specific
      neuronal alterations rather than stimulating the alpha(1)-adrenergic receptor.
      Additionally, this effect is enhanced in SHR.

PMID- 12183011
TI  - Response properties of periodontal mechanoreceptors in rats, in vitro.
AB  - Single unit activities of the inferior alveolar nerve evoked by calibrated von
      Frey stimuli (1.1, 2.9, 7.8, 11.8, and 17.2mN) on the periodontal ligaments of
      the mandibular molars or incisors were recorded in an in vitro jaw-nerve
      preparation of Wistar albino rats. The data of 55 (lower incisor) and 100 (lower
      molars) units were collected in the present study. Both rapidly (RA) and slowly
      adapting (SA) type units were found in the incisors, and most of these units were
      innervated by Abeta fibers. While all the units of the molars were of RA types,
      the innervated fibers of two-thirds (67/100) of the units have been identified as
      Adelta fibers. The response patterns of the RA type were subdivided into three
      types (ON, OFF or ON-OFF type) both in the incisors and the molars. While von
      Frey thresholds of all incisor units were 11.8 mN except one unit that was 7.8
      mN, those of the molars varied from 2.9 to 11.8 mN. In the molars, a majority of
      afferents innervated the periodontal ligaments of more than one tooth. This study
      suggests that response properties of periodontal mechanoreceptors are different
      between the incisors and the molars in rats, suggesting that these receptors have
      different functions in the regulation of mastication.

PMID- 12183012
TI  - Adrenalectomy abolishes the food-induced hypothalamic serotonin release in both
      normal and monosodium glutamate-obese rats.
AB  - Corticosteroids influence energy homeostasis through centrally-mediated
      stimulation of energy intake and inhibition of expenditure, while central
      serotonin (5-HT) has opposite effects. Both serotonergic dysfunction and high
      glucocorticoid levels may be relevant in obesity. The neurotoxin monosodium
      glutamate (MSG) induces a non-hyperphagic and hypometabolic obesity with
      hypercorticosteronemia. We investigated the influence of corticosterone levels on
      the serotonergic system of MSG-obese and control rats. Applying microdialysis, we
      found a similar feeding-induced stimulation of serotonin release in the lateral
      hypothalamus (LH) in sham-adrenalectomized control and MSG rats. The concomitant
      serum corticosterone variations were markedly distinct between them, in that an
      increase occurred in the control group, while the initially high levels of the
      MSG rats decreased with feeding. It is suggested that this lowering of
      corticosterone prevented a higher serotonergic activation, which would lead to a
      higher meal-induced thermogenesis and a better adequation of the caloric intake
      to a low metabolism. Adrenalectomy completely abolished the feeding-evoked
      serotonergic stimulation in both groups. This observation demonstrates that
      glucocorticoids are necessary for food intake to acutely stimulate 5-HT release
      and indicates that serotonergic activity in the LH is not likely to participate
      in the adrenalectomy-induced attenuation of the MSG-obesity.

PMID- 12183013
TI  - Discharge patterns evoked by depolarizing current injection in basal optic
      nucleus neurons of the pigeon.
AB  - The nucleus of the basal optic root of the accessory optic system in birds is
      involved in optokinetic nystagmus, which stabilizes images on the retina by
      compensatory movements of the eyes. The present paper studies the physiological
      and morphological properties of basal optic neurons in the pigeon by using a
      brain slice preparation and intracellular recordings. Sixty-one cells examined
      could be categorized into six types based on their firing patterns in response to
      depolarizing current injection. Type I cells (54%) fire spontaneously and more
      spikes as current intensity is increased. Type II cells (15%) discharge regular
      spikes with similar interspike intervals. Type III cells (5%) show an early burst
      followed by tonic firing. Type IV cells (5%) fire regular bursts with similar
      interburst intervals. Type V cells (16%) fire a few spikes in a cluster only at
      onset of current application. Type VI cells (5%) produce a hump-like
      depolarization or a single spike depending on current intensities. Seventeen
      cells stained with Lucifer yellow have multipolar or piriform perikarya (15-28
      microm) with two to eight primary dendrites. In some cases, an axon is observed
      to originate from the cell body, traveling dorsolaterally or dorsally. The
      physiological significance of these findings is discussed.

PMID- 12183014
TI  - Microinjection of procaine into the pedunculopontine tegmental nucleus suppresses
      hippocampal theta rhythm in urethane-anesthetized rats.
AB  - It was found that the cholinergic component of the pedunculopontine tegmental
      nucleus (PPN) is involved in the generation of theta rhythm in the hippocampus.
      However, it is still not known how important PPN is in the brainstem theta
      generating system, where the nucleus reticularis pontis oralis is regarded as a
      primary generator. In the present experiment, performed on urethane-anesthetized
      rats, we studied the effect on the tail pinch-elicited hippocampal theta of
      unilateral inactivation of PPN by means of direct procaine microinjection.
      Procaine induced ipsilateral suppression of theta rhythm, manifested as
      desynchronization of hippocampal EEG, a shift of the fast Fourier transformation
      (FFT) power peak toward lower frequencies, and a reduction of FFT peak magnitude
      at theta band. Hippocampal field activity returned to normal (both its FFT peak
      frequency and magnitude) within 30 min after the injection. The results obtained
      indicate that PPN is critical for hippocampal theta generation but it may not be
      involved in encoding theta frequency.

PMID- 12183016
TI  - Mu-opioid receptors in seizure-controlling brain structures are altered by
      prenatal morphine exposure and by male and female gonadal steroids in adult rats.
AB  - The present study used autoradiography to examine the effect of prenatal morphine
      exposure on mu-opioid receptor density in epileptic seizure-controlling brain
      structures including the substantia nigra pars compacta (SNC), substantia nigra
      pars reticulata (SNR), superior colliculus (SC), and subthalamic nucleus (STN) of
      adult male and female rats. The results demonstrate that prenatal morphine
      exposure increases the mu-opioid receptor density in the SNC and STN, but not in
      the SNR or in the SC of gonadally intact adult male rats. The density of mu
      opioid receptors in the SNC and STN is, however, decreased following gonadectomy
      in morphine-exposed males, and testosterone treatment fails to restore this
      decrease to the level of gonadally intact males. Further, in the SC, the density
      of mu receptors was lower in both saline-exposed, gonadectomized (GNX) and GNX,
      TP-treated males and in morphine-exposed, GNX, TP-treated males relative to
      gonadally intact saline- and morphine-exposed males, respectively. In
      ovariectomized (OVX) female rats, the same prenatal morphine exposure increases
      the mu-opioid receptor density in the SNC and SNR, but decreases it in the STN.
      The density of mu-opioid receptors is also decreased in the SNC and SC of OVX
      estrogen-treated females and in the SNR and SC of OVX, progesterone-treated
      females. Thus, the present study demonstrates that mu-opioid receptors in seizure
      controlling brain structures are sex-specifically altered by prenatal morphine
      exposure in adult progeny. Further, prenatal morphine exposure alters gonadal
      hormone effects on the density of mu receptors in adult, OVX females.

PMID- 12183015
TI  - Developmental expression and activity variation of nitric oxide synthase in the
      brain of golden hamster.
AB  - Nitric oxide (NO) is the downstream effector after the activation of N-methyl-D
      aspartate (NMDA) receptors. It is involved in various physiological processes,
      such as synapse reconstruction and plasticity, neurotoxity and neuronal death. It
      also participates in the development and maturation of cortical neurons. The
      expression of nitric oxide synthase (NOS) during the postnatal development of the
      visual cortex was investigated by both electron spin resonance (ESR) and Western
      blot methods. A typical spectrum of (DETC)(2)-Fe(II)-NO complex was found in the
      visual cortex of different age golden hamsters by ESR method. The signal
      intensity increased after birth, peaked at postnatal day 14 (PD14) and then
      gradually decreased. An analysis of variance (ANOVA) implied that the NO synthase
      expression significantly correlated with the developmental processes (p < 0.05).
      Results of Western blot further confirmed (one-way ANOVA, p < 0.05) the
      developmental relating expression pattern of NO synthase shown by ESR technique.

PMID- 12183017
TI  - Serotonin-stimulated glutamate release from an SCN explant culture was higher
      during light period.
AB  - Serotonin (5-HT) and glutamate are concerned with the input pathways to the
      suprachiasmatic nucleus (SCN), a center of biological rhythms in mammals. Arg
      vasopressin (AVP) is one of the output paths from the SCN to other brain areas.
      Functional relations of 5-HT on glutamate release, which stimulates AVP release,
      were therefore analyzed in an SCN slice culture using a glutamate biosensor.
      Spontaneous release of glutamate from the SCN culture was higher during the light
      period than the dark period. The 5-HT-stimulated increase in glutamate release
      was also larger at 0900 h than at 2000 h. In addition, glutamate, but not 5-HT,
      increased the AVP release. These findings suggest the possibility that the 5-HT
      has no direct facilitatory functions in AVP release via liberation of glutamate
      from the SCN.

PMID- 12183018
TI  - Effects of interleukin-1 beta on the steroid-induced luteinizing hormone surge:
      role of norepinephrine in the medial preoptic area.
AB  - Interleukin-1beta (IL-1beta), a cytokine, is known to inhibit the preovulatory
      surge of luteinizing hormone (LH); however, the mechanism by which it does so is
      unclear. This study was done to see if this effect is mediated through
      hypothalamic catecholamines. Adult female Sprague-Dawley rats were ovariectomized
      and implanted with a push-pull cannula in the medial preoptic area (MPA) of the
      hypothalamus. They were injected subcutaneously with 30 microg of Estradiol on
      the day 8 after surgery and with 2mg of Progesterone on day 10 at 1000 h. On the
      day of perfusion (day 10), the rats were injected with IL-1beta or its vehicle at
      1300 h. Perfusate samples from the MPA and blood samples from a jugular catheter
      were collected from 1300 to 1800 h. Catecholamine concentrations in the perfusate
      were measured using high performance liquid chromatography (HPLC)-EC and LH
      levels in the serum using RIA. Norepinephrine release in the MPA of control rats
      increased significantly at 1530, 1600, and 1630 h paralelling an increase in LH
      at 1600 h. In contrast, IL-1beta treatment blocked the LH surge and the rise in
      norepinephrine release in the MPA. No changes were observed in dopamine release,
      both in control and IL-treated animals. These results demonstrate for the first
      time that IL-induced suppression of the LH surge is probably mediated through
      inhibition of norepinephrine release in the MPA.

PMID- 12183019
TI  - The effect of corpus callosum agenesis on neocortical thickness and neuronal
      density of BALB/cCF mice.
AB  - We used acallosal and normal adult BALB/cCF mice to test the hypothesis that the
      development of the corpus callosum is relevant for the establishment of a normal
      structure of the neocortex. Neuronal density and thickness of individual layers
      were analyzed in neocortical regions with abundant callosal connections (area 6
      and the 17/18a border) and in the relatively acallosal area 17. In area 6,
      acallosal mice exhibited a total neocortical thickness smaller than that of
      normal mice, as well as thinner layers II+III and IV. Similar data were obtained
      at the 17/18a border, where the total thickness of the cortex and of layers
      II+III was smaller in the acallosal mice than in normal ones. In contrast, no
      significant thickness differences were documented in area 17 of acallosal versus
      normal mice. The quantitative data obtained in the analyzed neocortical regions
      did not show differences in neuronal density between acallosal and normal mice.
      The reduced cortical thickness, associated with the comparatively normal neuronal
      density in neocortical regions which normally have abundant callosal connections,
      provides indirect indication of a reduction in the number of cortical neurons in
      acallosal mice. This assumption was also supported by the lack of evidence of
      neocortical alterations in the acallosal area 17. The present findings suggest
      that during development neocortical neurons destined to receive a massive
      callosal input may die as a result of lack of afferents. Altogether the present
      data indicate that the input provided by callosal axons is necessary for a normal
      development of the neocortex.

PMID- 12183021
TI  - Increased levels of 3-hydroxykynurenine in different brain regions of rats with
      chronic renal insufficiency.
AB  - Tryptophan (TRP) metabolism via the kynurenine pathway leads to formations of
      neuroactive substances like kynurenine (KYN) and 3-hydroxykynurenine (3-HK),
      which may be involved in the pathogenesis of several human brain diseases. 3
      Hydroxykynurenine especially is known to have strong neurotoxic properties. The
      generation of reactive oxygen species (ROS) leads to neuronal cell death with
      apoptotic features. Because the chronic renal insufficiency (CRI) results in
      disturbances in the functioning of the central nervous system (CNS), it is
      conceivable that the metabolism of some kynurenines may be altered and could play
      an important role in uremic encephalopathy. The levels of TRP, KYN and 3-HK were
      measured in the plasma and in different brain regions of uremic rats. The total
      plasma concentration of TRP as well as in all the studied brain samples was
      significantly diminished during uremia. Surprisingly, the level of KYN and 3-HK
      were elevated both in the plasma and different brain regions of CRI animals. KYN
      concentrations were approximately two times higher in the cerebellum, midbrain
      and cortex compared to the control group. The changes of 3-HK levels were more
      pronounced in the striatum and medulla than in other structures. This data
      suggests that CRI results in deep disturbances on the kynurenine pathway in CNS,
      which could be responsible for neurological abnormalities seen in uremia.

PMID- 12183020
TI  - Alterations of the neocortical GABAergic system in the pilocarpine model of
      temporal lobe epilepsy: neuronal damage and immunocytochemical changes in chronic
      epileptic rats.
AB  - A wealth of previous studies reported pathological alterations in
      extrahippocampal regions in mesial temporal lobe epilepsy. Previous experimental
      findings have also demonstrated that the entorhinal cortex and the neocortex are
      damaged in different animal models of acute limbic seizures. The present study
      was aimed at verifying possible alterations in neocortical areas, and, in
      particular, structural changes of GABAergic interneurons in the sensorimotor
      cortex, in pilocarpine-induced chronic epilepsy in the rat. Series of sections
      were Nissl stained and processed for immunocytochemistry using antibodies that
      recognize nonphosphorylated neurofilament (SMI311), glial fibrillary acidic
      protein (GFAP), the calcium-binding protein parvalbumin (PV) which is expressed
      by a subset of cortical GABAergic neurons, the GABA transporter (GAT1), and
      isoform 65 of glutamic acid decarboxylase (GAD65), the GABA synthetic enzyme.
      Epileptic rats showed decreased cortical thickness, and diffuse gliosis was
      observed with GFAP antibody. Neurofilament alterations were also detected in
      sections processed using SMI311 antiserum. In addition, a diffuse decrease of PV,
      GAD65, and GAT1 immunoreactivity was observed in the sensorimotor cortex. Altered
      expression of PV, GAD65, and GAT1 pointed out specific neocortical disturbances
      in GABAergic inhibition, which could play a crucial role in seizure generation
      and expression. Thus, the present findings indicate that damage of GABAergic
      interneurons could be strictly associated with neocortical hyperexcitability in
      temporal lobe epilepsy.

PMID- 12183022
TI  - MR atlas of the baboon brain for functional neuroimaging.
AB  - Mathematical co-registration of functional image data (e.g., positron emission
      tomography, PET) to anatomical magnetic resonance (MR) imaging data allows for
      objective associations between function and anatomy. Baboons are often used as
      non-human primate models for functional neuroimaging studies. In this work, a
      digital MR-based high-resolution atlas of the baboon brain was generated and
      evaluated for PET. The atlas was generated from six SPGR-MR datasets (centered at
      mid-sagittal line, AC-PC orientation) that were transformed into the space of one
      representative MR, averaged and resampled into PET space. The atlas was evaluated
      by comparing blood flow and dopamine receptor and serotonin transporter binding
      measures determined using regions-of-interest (ROIs) generated on each individual
      co-registered MR (ROI(i)) and the atlas-defined ROI template (ROI(ATLAS)). Common
      ROIs applied to all data included frontal cortex, temporal cortex, thalamus,
      caudate, putamen and cerebellum. High correlations (r(2)>0.87) were found between
      the ROI(i) and ROI(ATLAS) data for all radiotracers (linear regression across
      ROIs for each baboon). The average regression slope values ranged from 0.95 to
      1.02 across radiotracers. Lastly, use of the atlas for statistical parametric
      mapping (SPM) of [15O]water data yielded good agreement with previous ROI(i)
      results. Overall, the digital MR-based atlas allowed for automatic co
      registration, proved useful across a range of PET Studies, and is accessible
      electronically via the Internet.

PMID- 12183023
TI  - Differential distribution of nerve fibers immunoreactive for substance P and
      calcitonin gene-related peptide in the superficial and deep muscle layers of the
      dorsum of the rat.
AB  - We compared the distribution of substance P (SP) and calcitonin gene-related
      peptide (CGRP) fibers of the superficial muscle layer (trapezius muscle), median
      muscle layer (rhomboideus muscle), and deep muscle layer (longissimus and
      spinalis muscles) of the dorsum of the rat. SP- and CGRP-immunoreactive fibers
      were seen along the walls of various types of blood vessels and within nerve
      bundles in skeletal muscles of all layers. Coexistence of SP and CGRP was evident
      in nerve fibers along the blood vessel walls. The total number of CGRP
      varicosities per millimeter square of muscle surface area was evaluated
      quantitatively, and CGRP varicosities were found to be significantly more
      numerous in the superficial muscle layer than in the deeper ones. After capsaicin
      treatment, most of the SP and CGRP fibers along the blood vessel walls were
      eliminated. These results suggest that sensory nerve fibers containing SP and
      CGRP are distributed more abundantly in the superficial muscle layer than in the
      deeper ones and that they might be involved in the regulation of local blood
      flow. The finding of SP- and CGRP-immunoreactive nerve fibers along the blood
      vessel walls connecting the trapezius muscle and the hypodermis raises the
      possibility that sensory stimuli to the skin affect the local blood flow of
      superficial muscle through collaterals of cutaneous fibers.

PMID- 12183024
TI  - The benzodiazepine partial inverse agonist Ro15-4513 alters anticonvulsant and
      lethal effects of carbamazepine in amygdala-kindled rats.
AB  - Ro15-4513 (ethyl-8-azido-5,6-dihydro-5methyl-6-oxo-4H-imidazo-[1,5-a]-1,4
      benzodiazepine-3-carboxylate), a benzodiazepine partial inverse agonist of the
      GABA(A) receptor, is known to protect against alcohol toxicities. The present
      study was designed to determine the role of Ro15-4513 in preventing
      anticonvulsant, toxic, and lethal effects of carbamazepine (CBZ) in amygdala
      kindled rats. Acute treatment with CBZ (25 mg/kg, i.p.) produced anticonvulsant
      effects in fully kindled rats characterized by a significant decrease in
      afterdischarge and seizure duration and stage. Repeated administration of this
      high dose of CBZ induced sedation and high (56%) lethality. The anticonvulsant
      and sedative effects of CBZ were strikingly suppressed by pretreatment with Ro15
      4513 (2.5 and 5 mg/kg, i.p.), and there was no mortality in animals co
      administrated with Ro15-4513 during the entire experimental period. These results
      indicate that Ro15-4513 protects against CBZ-induced sedation and lethality,
      while suppressing the anticonvulsant effects of CBZ, suggesting a role for the
      GABA(A) receptor in CBZ efficacy and side effects. The potential clinical
      implications for CBZ-induced toxicity and overdose remain to be explored.

PMID- 12183025
TI  - Oxidation induces autonomous activation of protein kinase C Apl I, but not
      protein kinase C Apl II in homogenates of Aplysia neurons.
AB  - The Ca(2+)-independent protein kinase C (PKC) Apl II, but not the Ca(2+)
      activated PKC Apl I, becomes autonomously active during intermediate periods of
      facilitation in Aplysia neurons. We examined the ability of superoxide formed by
      the enzymatic reaction of xanthine with xanthine oxidase (X/XO) to induce
      autonomous activity of PKCs in Aplysia. X/XO stimulated autonomous PKC activity
      in Aplysia nervous system homogenates, but this activity resulted solely from
      activation of PKC Apl I. PKC Apl I is also more sensitive to activation by X/XO
      when expressed in insect cells. Our results suggest that oxidation can
      autonomously activate PKC Apl I in the Aplysia nervous system, but that the
      activation of PKC Apl II during synaptic facilitation is not due to oxidation of
      the enzyme.

PMID- 12183026
TI  - Is sudden unexplained death in adult epileptic patients associated with
      geomagnetic disturbances at the day of death or the 4 days before?
AB  - Geomagnetic disturbances are controversially discussed as risk factor for sudden
      unexplained death in epilepsy (SUDEP). An autopsy-based cohort of 39 adult
      patients with definite SUDEP were compared to 102 epileptic patients with known
      cause of death (KCD), who died between 1981 and 1992. Most of them had suffered
      from therapy-resistant epilepsies, predominantly characterized by generalized
      tonic-clonic seizures (about 70%). We analyzed an international geomagnetic
      index, the mean planetary daily amplitude (Ap), and the appearance of storm
      sudden commencement (SSC) at the individual day of decease and the 4 days before
      (and after). The SUDEP and KCD patients did not substantially differ with respect
      to the Ap values (Mann-Whitney test; P>0.2) and frequency of SSC (Fisher test;
      P>0.2) at death or the 4 premortem days. In addition, Ap values above 50
      nanoTesla, postulated as critical threshold by other authors, showed no
      significant difference between SUDEP and KCD group for the day of death (5.1
      versus 3.9%) or the 4 days before (5.1 versus 11.8%) (Fisher test; P>0.2).
      Consequently, the current data did not support the hypothesis that geomagnetic
      activities may act as a relevant risk factor for SUDEP.

PMID- 12183027
TI  - Long-term depression of the human masseter inhibitory reflex.
AB  - Long-term depression (LTD) of synaptic transmission is reliably induced by low
      frequency stimulation (LFS) of nociceptive afferents in vitro. LTD can only
      exceptionally be induced in anesthetized animals. In order to fill the gap
      between the in vitro cell studies and the in vivo situation, the effects of LFS
      on the masseter inhibitory reflex (MIR) were investigated in man. Noxious LFS of
      mental nerve afferents caused a significant depression of the early MIR1 and the
      late MIR2 components. Whereas the onset latency (+25%), the duration (-42%) and
      the integral (+68%) of the MIR2 were strongly modulated after LFS, only the
      integral (+35%) of the MIR1 significantly changed. The results document a long
      term depression of trigeminal somatosensory processing in man. The different
      effects of LFS on the two components of the MIR may point to central mechanisms
      of LTD.

PMID- 12183028
TI  - The prion protein in human neurodegenerative disorders.
AB  - We evaluate cellular prion protein (PrP(C)) immunoreactivity (IR) in Alzheimer's,
      Parkinson's, diffuse Lewy body, and motor neuron diseases (MND), progressive
      supranuclear palsy, and multiple system atrophy. We use immunohistochemistry for
      PrP, including five monoclonal antibodies against different epitopes and three
      different pretreatments, alpha-synuclein, phosphorylated tau, beta-amyloid, and
      ubiquitin. Disease-specific inclusions are devoid of PrP(C) IR. Using double
      immunofluorescence and confocal laser microscopy we observe focal overlapping of
      PrP(C) with tau and with alpha-synuclein in early, but not in fully developed
      inclusions. However, PrP(C) IR neurons may contain abnormal tau or alpha
      synuclein aggregates. Additionally, we observe a loss of PrP(C) IR in anterior
      horn neurons in MND. Our results suggest that expression of PrP(C) reflects a
      general response to cellular stress rather than specific co-operation in
      aggregation of other proteins.

PMID- 12183029
TI  - Reduction of neurotransmitter release by the exogenous H3 domain peptide of HPC
      1/syntaxin 1A in cultured rat hippocampal neurons.
AB  - The membrane protein HPC-1/syntaxin 1A plays a key role in synaptic vesicle
      exocytosis in the presynaptic terminal. In particular, the H3 domain of HPC
      1/syntaxin 1A participates in several protein-protein interactions that regulate
      neurotransmitter release. To investigate H3 domain function in neurotransmitter
      release, we used paired whole-cell patch clamping to record the evoked inhibitory
      postsynaptic currents in cultured hippocampal neurons. Introducing H3 domain
      peptide into the presynaptic neuron with a patch electrode depressed
      neurotransmitter release in a stimulation-frequency-dependent manner. Recovery
      from synaptic vesicle depletion induced by tetanic stimulation was significantly
      slowed by exogenous H3 domain peptide. These results suggest that the H3 domain
      peptide reduces neurotransmitter release by retarding the refilling of readily
      releasable vesicles.

PMID- 12183031
TI  - Assessment of neuroprotective ability of a spin trap, alpha-phenyl-N-tert
      butylnitrone, against malonate-induced ischemic injury of rat brain by apparent
      water diffusion coefficient mapping.
AB  - Ischemic brain injury induced by injection of 3-micromol malonate into the left
      striatum of male Sprague-Dawley rats was examined by apparent water diffusion
      coefficient (ADC) mapping of magnetic resonance imaging. The region surrounding
      the injection core was imaged as a hypointense area in ADC mapping and ADC values
      in the regions were significantly decreased 3 and 6 h after ischemia. Significant
      reduction of the hypointense area and the recovery of ADC values were observed in
      rats to which alpha-phenyl-N-tert-butylnitrone (PBN) was intraperitoneally
      administered 1 h before ischemia. Since ADC mapping has been reported to be a
      suitable method for evaluating the extent and the degree of cytotoxic edema in
      the early period after the onset of ischemia, the present results prove that PBN
      is able to prevent early ischemic insults such as cytotoxic edema.

PMID- 12183030
TI  - Alpha(1)-adrenoceptor-mediated depolarization and beta-mediated hyperpolarization
      in cultured rat dorsal root ganglion neurones.
AB  - The mechanism of sympathetic - sensory coupling after nerve injury is still not
      well understood. We have studied the changes in resting potential and
      excitability of sensory neurones induced by adrenergic stimulation, using whole
      cell and perforated-patch recordings in cultured dorsal root ganglion neurones
      from normal rats. Adrenaline (1-100 microM) depolarized 18 of 39 neurones (46%)
      and hyperpolarized seven neurones (18%); excitability was increased and
      decreased, respectively. Stimulating the neurones with 10 microM phenylephrine
      (alpha(1)-agonist) induced depolarization and increased excitability, while 10
      microM isoprenaline (beta-agonist) induced hyperpolarization and reduced
      excitability. We conclude that alpha(1)- and beta-receptors have opposing effects
      on membrane potential and excitability in cultured dorsal root ganglion neurones,
      and the differing effects of adrenaline can be explained by different degrees of
      expression of each receptor type.

PMID- 12183032
TI  - Raloxifene effects upon the neuronal system controlling sexual receptivity in
      female rats.
AB  - Selective estrogen receptor modulators (SERMs) constitute a new family of drugs
      with growing interest in the management of estrogen-associated pathology.
      Raloxifene is a SERM that mimics estrogen action on bone and blood lipid
      concentration but whether it acts as estrogen in the central nervous system
      remains to be fully established. In the present communication, we aimed at
      evaluating the estrogenic/antiestrogenic effects of raloxifene upon organization
      and activation of sexual receptivity, an estrogen-dependent event, in female
      rats. To this end, the effects of raloxifene, administered during the neonatal
      period, were compared with those of estrogen in terms of disruption of sexual
      receptivity in estrogen-progesterone-primed ovariectomized (OVX) female rats. In
      addition, the ability of raloxifene to induce sexual receptivity in progesterone
      primed OVX females was analyzed. Similarly, the effects of the combined
      administration of estrogen and raloxifene were studied. Our results suggest that
      raloxifene does not act as estrogen upon the organization of the neuronal system
      involved in the control of sexual receptivity in female rats and exerted an
      antiestrogenic action in adult OVX estrogen-primed female rats.

PMID- 12183033
TI  - Seizure suppression by adenosine A(2A) receptor activation in a rat model of
      audiogenic brainstem epilepsy.
AB  - Adenosine is known to suppress seizure activity mainly by activation of adenosine
      A(1) receptors. However, little is known about the potential involvement of other
      types of adenosine receptors in seizure suppression. It was now tested whether
      activation of adenosine A(2A) receptors would be effective in the suppression of
      generalized brainstem seizures. Genetically epilepsy-prone rats were
      intraperitoneally injected with increasing doses of the A(2A) receptor agonist,
      5'-(N-cyclopropyl)-carboxamido-adenosine (CPCA), and, for comparison, with the
      A(1) receptor agonist, 2-chloro-N(6)-cyclopentyladenosine (CCPA). Both CPCA and
      CCPA were effective in suppressing generalized brainstem seizures with minimal
      effective concentrations of 2.5 and 1.5 mg/kg, respectively. Seizure suppression
      was maintained when CPCA was co-injected with the peripherally acting adenosine
      receptor antagonist 8-(p-sulphophenyl)theophylline, suggesting that central
      activation of A(2A) receptors effectively contributes to seizure suppression.

PMID- 12183034
TI  - Motor cortex excitability in Alzheimer disease: one year follow-up study.
AB  - Seventeen patients affected by Alzheimer disease (AD) underwent two transcranial
      magnetic stimulation (TMS) studies separated by an interval of 12 months, in
      order to monitor possible changes in motor cortex excitability. After the first
      examination, all patients were treated with cholinesterase inhibitor drugs. Motor
      threshold (MT), amplitude of motor evoked potentials and central motor conduction
      time were considered. After one year, the mean MT values showed a decrease
      significantly correlated with the severity of cognitive involvement, evaluated by
      means of the Mini Mental State Examination (MMSE). The difference in MT between
      the two recording sessions showed no significant correlation with the difference
      in MMSE score. One year of treatment with cholinesterase inhibitor drugs did not
      stop the progressive increase in motor cortex excitability. Serial analysis of
      TMS might represent a method to monitor the rate of change in motor cortex
      excitability in patients with AD.

PMID- 12183035
TI  - Expression of voltage-dependent calcium channel subunits in the rat retina.
AB  - The expression patterns of different Ca(2+) channel alpha(1) subunits (alpha(1A
      E)) were immunohistochemically studied in the rat retina. Intense
      immunoreactivity (IR) for alpha(1A) (P/Q-type) and alpha(1B) (N-type) Ca(2+)
      channels was observed in both the outer and inner plexiform layers (OPL and IPL).
      In addition, alpha(1B)-IR was found in the outer and inner nuclear layers.
      Staining for alpha(1E) (R-type) was diffusely distributed in all three nuclear
      layers and in the IPL. The alpha(1C) and alpha(1D), two L-type Ca(2+) channel
      subunits, exhibited distinct expression patterns, with alpha(1C) being almost
      exclusively expressed on bipolar cells, and alpha(1D) mainly on photoreceptor
      cell bodies and in the OPL. Staining for alpha(1D) was also observed on Muller
      cells. The differential expression pattern of the alpha(1) subunits suggests that
      these Ca(2+) channel subtypes may be associated with different retinal functions.

PMID- 12183036
TI  - Ontogenetic changes in neuropeptide Y-immunoreactive cerebrospinal fluid
      contacting neurons in the hypothalamus of the cloudy dogfish, Scyliorhinus
      torazame (Elasmobranchii).
AB  - Ontogenetic changes in neuropeptide Y-immunoreactive (NPY-ir) cerebrospinal fluid
      (CSF)-contacting neurons in the dogfish hypothalamus were studied
      immunohistochemically. NPY-ir CSF-contacting neurons first appeared in the median
      infundibular floor of the embryo at the 34 mm stage. At the 40 mm stage, similar
      neurons were found also in the saccus vasculosus (SV). The number of these
      neurons increased during the 54-80 mm stages, and the cells in the infundibular
      floor extended their basal processes to the neuropil of the median eminence,
      whereas the cells in the SV sent their axonal fibers to the tractus sacci
      vasculosi. After hatching, NPY immunoreactivity in the ventral hypothalamus
      became less dense, and the labeled CSF-contacting neurons tended to be confined
      to the nucleus lateralis tuberis, similarly as in the adults. The occurrence of
      NPY-ir CSF-contacting neurons in the SV was transient during the embryonic
      periods.

PMID- 12183037
TI  - Hyperexcitability of hippocampal CA1 neurons after fluid percussion injury of the
      rat cerebral cortex.
AB  - Effects of fluid percussion injury (FPI) of the parietal cerebral cortex on the
      neuronal activity in the temporal region of the rat hippocampal CA1 area were
      investigated by using optical and extracellular recording techniques. Application
      of moderate impact (1.5-2.0 atm) to the parietal cerebral cortex enhanced the
      optical signal of the neuronal activity in the ipsilateral hippocampal CA1 area.
      The field potential evoked by the Schaffer collaterals had multiple population
      spikes in the ipsilateral hippocampal CA1 pyramidal cell layer. Bicuculline (15
      microM) increased the amplitude and the number of population spikes of the field
      potential even after the brain injury. These results suggest that FPI produces
      hyperexcitability of hippocampal CA1 neurons, probably by increasing the activity
      of the Schaffer collaterals of hippocampal CA3 neurons.

PMID- 12183038
TI  - Repeated subinflammatory ultraviolet B irradiation increases substance P and
      calcitonin gene-related peptide content and augments mustard oil-induced
      neurogenic inflammation in the skin of rats.
AB  - The cutaneous neurosensory system is suggested to be involved in the
      pathophysiology of pruritus and skin diseases such as psoriasis. We investigated
      if repeated subinflammatory doses of ultraviolet B (UVB) irradiation similar to
      those used to treat pruritus or psoriasis would affect the cutaneous neurosensory
      system. Sprague-Dawley rats were irradiated thrice weekly for 2-4 weeks with
      subinflammatory doses of UVB. Three days after the last UVB exposure: (i), the
      skin contents of substance P (SP), calcitonin gene-related peptide (CGRP), and
      nerve growth factor (NGF) were quantified; (ii), the skin nerve fiber density was
      observed; and (iii), the effect of UVB on mustard oil-induced neurogenic
      inflammation was determined. UV exposure significantly increased SP and CGRP
      content and mustard oil-induced neurogenic inflammation in UV-irradiated but not
      non-irradiated skin; however, it did not affect cutaneous NGF content or overall
      nerve fiber density. These data suggest that repeated subinflammatory UVB
      irradiation locally increases the content of cutaneous SP and CGRP by an increase
      of neuropeptide content of nerve fibers rather than by an increase of overall
      nerve fiber density.

PMID- 12183039
TI  - A dynamic pattern analysis of coordination between breathing and rhythmic arm
      movements in humans.
AB  - We investigated the behavioral dynamics of human breathing-wrist movement
      coordination in a 1:1 frequency locking task. A pronation-supination wrist
      movement and a short trial duration were chosen to limit both mechanical and
      metabolic constraints on the respiratory system. Subjects voluntarily controlled
      their breathing rhythm to follow the metronome. We found that pronation
      expiration and pronation-inspiration patterns coexisted as the (sole) stable
      fixed-point attractors of the coordination system. The pronation-expiration
      pattern was more stable than the pronation-inspiration pattern. Depending on the
      oscillation frequency, this differential stability gave rise to both absolute and
      relative coordination. These results show that simple behavioral laws of
      coordination encapsulate neural coupling dynamics evidenced from experimental
      research in human beings and animals. They challenge the classical view that such
      a coupling is not present for all imposed movement frequencies. Rather, relative
      coordination emerges as a result of the modification of coupling strength with
      frequency. These results can be accommodated by the asymmetric version of the HKB
      model of coordination dynamics. Thus, our data suggest that the principles and
      models of coordination dynamics may be taken as a reference to study the coupling
      of the motor and physiological subsystems involved in breathing-movement
      coordination.

PMID- 12183040
TI  - Mitochondrial anomalies are associated with the induction of intrinsic cell death
      proteins-Bcl(2), Bax, cytochrome-c and p53 in mice brain during experimental
      fatal murine cerebral malaria.
AB  - The levels of apoptosis associated proteins Bcl(2), Bax, cytochrome-c and p53 was
      investigated in mice cerebral cortex and cerebellum, using an experimental model
      of fatal murine cerebral malaria (FMCM). Owing to the activation of events
      central to mitochondrial dysfunctions, we monitored the structural integrity of
      mitochondria in cerebral malaria (CM) infected brain tissue by transmission EM
      (TEM) studies. Western blot analysis revealed the induction of Bcl(2), Bax,
      cytochrome-c and p53 in both cortex and cerebellum. The TEM studies revealed
      extensive vacuolation and swelling of mitochondria in infected brain suggestive
      of a late stage of degeneration. Our results underscore the activation of an
      intrinsic cell death pathway as evinced by the induction of mitochondria
      associated apoptotic proteins Bcl(2), Bax and cytochrome-c and further envisages
      the induction of p53 as a possible continuation of the post receptor signaling
      events associated with tumor necrosis factor induction following inflammatory
      responses during CM. These findings may be crucial to mitochondrial dysfunctions
      underlying the pathology of FMCM.

PMID- 12183041
TI  - A trace amine, tyramine, functions as a neuromodulator in Drosophila
      melanogaster.
AB  - The tyramine receptor (TyrR) is a G protein-coupled receptor for trace amines,
      cloned in Drosophila melanogaster, and claimed to be either an octopamine
      receptor or a tyramine receptor. We previously reported that in the larval
      neuromuscular junctions, the modulatory effect on the excitatory junction
      potentials of tyramine is distinctly different from that of octopamine. The
      effect of tyramine but not of octopamine was selectively abolished in the TyrR
      mutant hono, suggesting that this gene encodes a receptor for tyramine, and not
      for octopamine. We examined whether there was a gene-dosage effect of this
      tyramine modulation using combinations of hono, deficiency (Df) and wild-type
      alleles. The tyramine effect was observed in hono heterozygotes (+/hono), which
      showed intermediate levels of response, but was not seen in +/Df or hono/Df
      hemizygotes. While these further suggest that tyramine is the true ligand, it is
      possible that the gene-dosage effect is only evident above some threshold of gene
      expression levels. Immunohistochemical staining using an anti-tyramine antibody
      identified tyramine-containing neurons in the larval central nervous system, some
      of which were distinct from the octopamine-containing neurons. Taken together,
      these results strongly suggest that tyramine functions as a neuromodulator.

PMID- 12183042
TI  - Attention-related modifications of ultra-late CO(2) laser evoked potentials to
      human trigeminal nerve stimulation.
AB  - Our study aimed at investigating the scalp topography of ultra-late CO(2) laser
      evoked potentials (LEPs), which are related to C fiber activation, and at
      exploring the effect of attention deviation on ultra-late LEPs. Brain responses
      to non-painful CO(2) laser stimuli were recorded in ten healthy subjects in three
      different conditions: (i) neutral condition in which subjects did not have any
      task; (ii) distraction condition in which subjects were asked to perform a
      mathematical task; and (iii) attention condition in which subjects had to count
      the number of stimuli. In all subjects, also A fiber-related late LEPs were
      recorded after painful CO(2) laser stimulation. The ultra-late LEPs in attention
      condition included an earlier negative potential (ultra-late N1) in the
      contralateral temporal region and a simultaneous frontal positive response (ultra
      late P1). Later, a vertex biphasic component (ultra-late N2a and ultra-late P2)
      was identifiable. The vertex ultra-late LEP amplitude was significantly decreased
      in both neutral and distraction condition. Ultra-late LEPs showed a longer
      latency than late LEPs, but the scalp distributions of both ultra-late and late
      LEPs were very similar, thus suggesting that the same cerebral areas may be
      involved in their generation. Since attention deviations have a strong effect on
      ultra-late LEP amplitude, the subject's attention should be addressed to CO(2)
      laser stimuli when ultra-late LEPs are used for clinical purposes.

PMID- 12183043
TI  - Acetyl-L-carnitine shows neuroprotective and neurotrophic activity in primary
      culture of rat embryo motoneurons.
AB  - We evaluated the role of acetyl-L-carnitine (ALCAR) in protecting primary
      motoneuron cultures exposed to excitotoxic agents or serum-brain derived
      neurotrophic factor (BDNF) deprived. To exclude that ALCAR works as a metabolic
      source, we compared its effects with those of L-carnitine (L-CAR), that seems to
      have no neurotrophic effect. A concentration of 10 mM ALCAR, but not L-CAR,
      significantly reduced the toxic effect of 50 microM N-methyl-D-aspartate (NMDA, %
      viability: NMDA 45.4+/-2.80, NMDA+ALCAR 90.8+/-11.8; P<0.01) and of 5 microM
      kainate in cultured motoneurons (% viability: kainate 40.66+/-10.73;
      kainate+ALCAR 63.80+/-13.88; P<0.05). The effect was due to a shift to the right
      of the dose-response curve for kainate (EC50 for kainate 5.99+/-1.012 microM;
      kainate+ALCAR 8.62+/-1.13 microM; P<0.05). ALCAR, but not L-CAR, significantly
      protected against BDNF and serum-deprivation reducing the apoptotic cell death (%
      viability respect to control: without BDNF/serum 61.8+/-13.3: without
      BDNF/serum+ALCAR 111.8+/-13.9; P<0.01). Immunocytochemistry showed an increase in
      choline acethyltransferase and tyrosine kinaseB receptors in motoneurons treated
      with ALCAR but not with L-CAR. These results suggest that ALCAR treatment
      improves the motoneurons activity, acting as a neurotrophic factor.

PMID- 12183044
TI  - Ghrelin injected into the paraventricular nucleus of the hypothalamus of male
      rats induces feeding but not penile erection.
AB  - The effect of ghrelin, a recently characterized endogenous receptor agonist for
      growth hormone (GH) secretagogue receptors, on feeding and penile erection was
      compared with that of EP 80661, a peptide analogue of the GH secretagogue
      hexarelin, previously identified for its pro-erectile activity when injected into
      the paraventricular nucleus of the hypothalamus of male rats. Ghrelin (0.01-1
      microg), but not EP 80661 (0.02-1 microg), was found to be particularly effective
      in enhancing feeding. The minimal effective dose of ghrelin was 0.1 microg, which
      increased food intake by 88%, while the maximal response (355% above control
      values) was found with 1 microg of the peptide. The enhancing effect of ghrelin
      on feeding was prevented by the prior administration of the neuropeptide Y Y5
      receptor antagonist (DTyr(2), DThr(32)) neuropeptide Y (NPY, 10 microg), but not
      by the GH-RH receptor antagonist MZ-4-71 (10 microg), or by EP 91073, a hexarelin
      analogue that antagonizes the pro-erectile effect of EP 80661 (10 microg), given
      into the lateral ventricles. In contrast, ghrelin failed to induce penile
      erection at all doses tested, while EP 80661 induced penile erection in a dose
      dependent manner. The pro-erectile effect of EP 80661 was prevented by EP 91073
      (10 microg), but not by (DTyr(2), DThr(32)) NPY (10 microg) or by the GH-RH
      receptor antagonist MZ 4-71 (10 microg), given into the lateral ventricles. The
      present results provide further support to the hypothesis that the GH
      secretagogue receptors mediating feeding are different from those mediating
      penile erection and activated by pro-erectile EP peptides.

PMID- 12183045
TI  - Deoxycorticosterone stimulates the activity of nicotinamide adenine dinucleotide
      phosphate-diaphorase/nitric oxide synthase immunoreactivity in hypothalamic
      nuclei of rats.
AB  - Mineralocorticoids (MC) play an important role in development of salt appetite.
      Part of this effect involves the hypothalamic paraventricular (PVN) and
      supraoptic (SON) nuclei, in which MC treatment increases arginine vasopressin
      (AVP) synthesis and release. Since the AVP system is also modulated by nitric
      oxide (NO), we studied if deoxycorticosterone acetate (DOCA) treatment changed
      the number of nicotinamide adenine dinucleotide phosphate-diaphorase (NADPH-d)
      active neurons and neuronal NO synthase (nNOS)-immunoreactive (IR) cells in the
      PVN and SON. After four injections of DOCA (10 mg/rat per day), rats developed a
      salt appetite and increased NADPH-d active and nNOS-IR neurons in both nuclei. A
      single DOCA injection did not change salt consumption or nNOS-IR cells, but
      increased the number of NADPH-d positive neurons in the PVN only. Therefore,
      while acute MC treatment stimulated the activity of pre-existing enzyme, chronic
      steroid treatment recruited additional neurons showing nNOS
      immunoreactivity/NADPH-d activity. These data suggest a role for NO produced in
      the PVN and SON in DOCA stimulatory effects on AVP mRNA and salt appetite.

PMID- 12183046
TI  - Role of N-methyl-D-aspartate receptors and the nitric oxide pathway in
      nociception/hyperalgesia elicited by protease-activated receptor-2 activation in
      mice and rats.
AB  - Activation of the peripheral protease-activated receptor-2 (PAR-2) triggers
      nociceptive behaviour and thermal hyperalgesia in rats. The present study created
      a novel mouse model for PAR-2-triggered nociception, and then examined the roles
      of NMDA receptors and the nitric oxide (NO) pathway in nociceptive processing by
      PAR-2. Intraplantar administration of the PAR-2 agonist SLIGRL-NH(2) elicited
      nociceptive responses in mice, an effect being more specific in mast cell
      depleted mice. This PAR-2-triggered nociception was abolished by the NMDA
      receptor antagonist MK-801, but not the neuronal NO synthase inhibitor 7-nitro
      indazole. In contrast, the PAR-2-triggered thermal hyperalgesia in rats was
      blocked by both agents. Our study thus provides a novel mouse model for PAR-2
      mediated nociception, and suggests that NMDA receptors are involved in PAR-2
      triggered nociception and hyperalgesia, while NO contributes only to the latter.

PMID- 12183047
TI  - Cyclooxygenase-2-deficient mice are resistant to 1-methyl-4-phenyl1, 2, 3, 6
      tetrahydropyridine-induced damage of dopaminergic neurons in the substantia
      nigra.
AB  - Cyclooxygenases (COX), key enzymes in prostanoid biosynthesis, may represent
      important therapeutic targets in various neurodegenerative diseases. In the
      present study, we explored the role of COX in Parkinson's disease (PD) by using 1
      methyl-4-phenyl1, 2, 3, 6-tetrahydropyridine (MPTP) as a tool to create a rodent
      Parkinsonian model. MPTP (20 mg/kg, subcutaneously) was injected daily into COX-1
      and COX-2-deficient mice and wild-type (WT) controls for five consecutive days.
      Immunocytochemical analysis of tissues collected 7 days after the final MPTP
      treatment showed that MPTP significantly decreased the number of tyrosine
      hydroxylase-immunoreactive (TH-ir) neurons in the substantia nigra pars compacta
      (SNc) of WT (40% decrease) and COX-1(-/-) (45% decrease) mutants. However, a much
      smaller loss of TH-ir neurons in COX-2(-/-) mutants (20% decrease) was observed.
      Furthermore, electrochemical analysis revealed a more than 70% decrease in the
      levels of dopamine and its metabolites (3,4-dihydroxyphenylacetic acid and
      homovanillic acid) in the striatum of the WT control COX-1(-/-) and COX-2(-/-)
      mutant mice. These results indicate that loss of COX-2 activity reduces MPTP
      induced damage to the dopaminergic neurons of the SNc, but does not alter the
      levels of dopamine and its metabolites in the striatum. Interestingly, MPTP
      caused the same degree of loss of dopaminergic neurons in both COX-2(+/-) and COX
      2(-/-) mice (20% loss). The results of this study indicate an important role of
      COX-2 in MPTP-induced neuronal degeneration and suggest the possibility that
      manipulation of the COX-2 could be an important target for therapeutic
      interventions in PD.

PMID- 12183048
TI  - Effect of amphetamine repeated treatment on the feeding behavior in neuropeptide
      Y-overexpressing mice.
AB  - The preset study examined the hypothesis that an increase of brain neuropeptide Y
      (NPY), an orexigenic peptide, might decrease the action of amphetamine (AMPH), a
      well-known anorectic agent. Transgenic mice overexpressing the NPY gene were used
      to compare with the wild-type control. AMPH-induced anorexia is documented to
      mediate through the release of dopamine (DA), via an activation of D(1)- and D(2)
      subtype receptors, to affect the hypothalamic NPY. Thus, co-administration of
      D(1)/D(2) agonists was also performed to mimic the action of AMPH. The mice of
      NPY-overexpressing (NPY-OX) and wild-type groups were administered with AMPH or a
      combination of D(1)/D(2) agonists repeatedly for 5 days. We found that repeated
      AMPH administration-induced anorexia in wild-type mice was longer (at the initial
      3 days) than that in NPY-OX mice (only at the first day). Moreover, repeated co
      administration of D(1)/D(2) agonists significantly exerted a continuous anorectic
      effect in wild-type mice, but exerted a significant effect only at the first day
      in NPY-OX mice. These results indicated that the anorectic effect of AMPH decayed
      faster in NPY-OX mice and suggested that NPY expression by the stimuli could
      counteract the anorectic effect of AMPH. Thus, NPY can be considered to play a
      functional role in the regulation of AMPH-induced anorexia in mice.

PMID- 12183049
TI  - Identification of methylated proteins by protein arginine N-methyltransferase 1,
      PRMT1, with a new expression cloning strategy.
AB  - Methylation at arginines has recently come to attention as a posttranslational
      modification of proteins, which is implicated in processes from signaling,
      transcriptional activation, to mRNA processing. Here we report that several
      proteins extracted from HeLa cells were methylated by PRMT1 (protein arginine N
      methyltransferease 1) even on a nitrocellulose membrane, while proteins from
      Escherichia coli are not methylated with this protein. Screening PRMT1 substrates
      from a lambdagt11-HeLa cDNA library, we found that more than half of the 48 cDNA
      clones obtained encode putative RNA-binding proteins that have RGG (arginine
      glycine-glycine) motifs, such as hnRNP R (heterogeneous nuclear ribonucleoprotein
      R) and hnRNP K. We cloned two novel arginine methylation substrates, ZF5 (zinc
      finger 5) and p137GPI (GPI-anchor protein p137), which do not possess typical RGG
      motifs. We also cloned a novel protein that has RGG motifs, but does not have any
      other RNA-binding motifs. We tentatively termed this clone SAMT1 (substrate of
      arginine methyl transferase 1). A(63-)VLD(-65) to AAA mutation of PRMT1
      suppressed the methylation of recombinant SAMT1 and other RGG proteins in the
      HeLa extracts. This systematic screening of substrate proteins with the solid
      phase methylation reaction will contribute to identify new roles of PRMT family.

PMID- 12183050
TI  - Origins and consequences of mitochondrial decline in nucleated erythrocytes.
AB  - Cellular aging in nucleated erythrocytes from lower vertebrates is accompanied by
      losses in mitochondria but it remains unclear (i) how these losses accrue (ii) if
      these changes alter energetics and (iii) whether such changes increase the
      propensity for apoptosis. We addressed these questions using trout erythrocytes
      that were separated into age classes using inherent differences in buoyant
      density. The oldest cells showed a profound decline in mtDNA transcripts, due to
      reductions in both transcription (90% decline in total RNA) and mtDNA copy number
      (35%). No alterations in the ratio of 16S rRNA to COX I mRNA were detected, nor
      was there an accumulation of unprocessed mtDNA transcripts. While older cells had
      reduced basal respiration, there were no changes in mitochondrial enzymes
      stoichiometries, tissue ATP levels or dinitrophenol-induced (maximal) respiration
      rates. Apoptosis could not be induced in either whole blood, young or old
      erythrocytes by pro-oxidants, mitochondrial inhibitors or staurosporine. In
      contrast, cyclosporin A (CsA) caused caspase 3 activation, DNA laddering and LDH
      leakage, but only in young cells. Both CsA and a combination of azide, oligomycin
      and dinitrophenol cause mitochondrial depolarization and caspase 9 activation,
      but only CsA induced caspase 3 and apoptosis. Caspase inhibitor studies support
      the conclusion that mitochondrial changes may accompany CsA-induced cell death,
      but are not essential in its progression. While pifithrin failed to induce cell
      death, it enhanced the effects of CsA, implicating a role for p53. Collectively,
      these studies suggest that the mitochondrial changes with aging do not compromise
      cellular function, although trout erythrocytes can initiate apoptosis by non
      mitochondrial pathways.

PMID- 12183051
TI  - A rapid, nongenomic action of glucocorticoids in rat B103 neuroblastoma cells.
AB  - We report here a new example in which glucocorticoids (GCs) acted in a rapid,
      nongenomic way. In rat B103 neuroblastoma cells, 5-hydroxytryptamine (5-HT) was
      found to evoke an immediate rise in intracellular free calcium concentration
      ([Ca(2+)](i)). Pre-incubation of B103 cells for 5 min with corticosterone (B) or
      bovine serum albumin-conjugated corticosterone (B-BSA) concentration-dependently
      (10(-4)-10(-8) M) inhibited the peak increments in [Ca(2+)](i). Cortisol and
      dexamethasone had a similar effect, while deoxycorticosterone and cholesterol
      were ineffective. This rapid inhibitory effect of corticosterone could be
      mimicked by protein kinase C (PKC) activator phorbol 12-myristate 13-acetate
      (PMA) and abolished completely by PKC inhibitors Ro31-8220 or GF-109203X. Neither
      pertussis toxin (PTX) nor nuclear GC receptor (GR) antagonist RU38486 influenced
      the rapid action of B. Our results suggest that GCs can modulate the 5-HT-induced
      Ca(2+) response in B103 cells in a membrane-initiated, nongenomic, and PKC
      dependent manner.

PMID- 12183052
TI  - Defensin-rich granules of human neutrophils: characterization of secretory
      properties.
AB  - The various granule subtypes of the human neutrophil differ in propensity for
      exocytosis. As a rule, granules formed at late stages of myelopoiesis have a
      higher secretory potential than granules formed in more immature myeloid cells.
      Neutrophils contain four closely related alpha-defensins, which are stored in a
      subset of azurophil granules. These defensin-rich azurophil granules (DRG) are
      formed later than defensin-poor azurophil granules, near the
      promyelocyte/myelocyte transition. In order to characterize the secretory
      properties of DRG, we developed a sensitive and accurate ELISA for detection of
      the neutrophil alpha-defensins HNP 1-3. This allowed us to quantify the
      exocytosis of alpha-defensins and markers of azurophil (myeloperoxidase),
      specific (lactoferrin) and gelatinase (gelatinase) granules from neutrophils
      stimulated with different secretagogues. The release pattern of alpha-defensins
      correlated perfectly with the release of myeloperoxidase and showed no
      resemblance to the exocytosis of lactoferrin or gelatinase. This finding was
      substantiated through subcellular fractionation experiments. In conclusion,
      despite a distinct profile of biosynthesis, DRG are indistinguishable from
      defensin-poor azurophil granules with respect to exocytosis. Thus, in contrast to
      peroxidase-negative granules, azurophil granules display homogeneity in their
      availability for extracellular release.

PMID- 12183053
TI  - CD44 stimulation by fragmented hyaluronic acid induces upregulation and tyrosine
      phosphorylation of c-Met receptor protein in human chondrosarcoma cells.
AB  - Hepatocyte growth factor/scatter factor (HGF/SF) can induce proliferation and
      motility and promote invasion of tumor cells. Since HGF/SF receptor, c-Met, is
      expressed by tumor cells, and since stimulation of CD44, a transmembrane
      glycoprotein known to bind hyaluronic acid (HA) in its extracellular domain, is
      involved in activation of c-Met, we have studied the effects of CD44 stimulation
      by ligation with HA upon the expression and tyrosine phosphorylation of c-Met on
      human chondrosarcoma cell line HCS-2/8. The current study indicates that (a) CD44
      stimulation by fragmented HA upregulates expression of c-Met proteins; (b)
      fragmented HA also induces tyrosine phosphorylation of c-Met protein within 30
      min, an early event in this pathway as shown by the early time course of
      stimulation; (c) the effects of HA fragments are critically HA size-dependent.
      High molecular weight HA is inactive, but lower molecular weight fragments (M(r)
      3.5 kDa) are active with maximal effect in the microg/ml range; (d) the standard
      form of CD44 (CD44s) is critical for the response because the effect on c-Met,
      both in terms of upregulation and phosphorylation, is inhibited by preincubation
      with an anti-CD44 monoclonal antibody; and (e) phosphorylation of c-Met induced
      by CD44 stimulation is inhibited by protein tyrosine kinase inhibitor,
      tyrphostin. Therefore, our study represents the first report that CD44
      stimulation induced by fragmented HA enhances c-Met expression and tyrosine
      phosphorylation in human chondrosarcoma cells. Taken together, these studies
      establish a signal transduction cascade or cross-talk emanating from CD44 to c
      Met.

PMID- 12183054
TI  - cDNA array reveals mechanosensitive genes in chondrocytic cells under hydrostatic
      pressure.
AB  - Hydrostatic pressure (HP) has a profound effect on cartilage metabolism in normal
      and pathological conditions, especially in weight-bearing areas of the skeletal
      system. As an important component of overall load, HP has been shown to affect
      the synthetic capacity and well-being of chondrocytes, depending on the mode,
      duration and magnitude of pressure. In this study we examined the effect of
      continuous HP on the gene expression profile of a chondrocytic cell line (HCS
      2/8) using a cDNA array containing 588 well-characterized human genes under tight
      transcriptional control. A total of 51 affected genes were identified, many of
      them not previously associated with mechanical stimuli. Among the significantly
      up-regulated genes were immediate-early genes, and genes involved in heat-shock
      response (hsp70, hsp40, hsp27), and in growth arrest (GADD45, GADD153,
      p21(Cip1/Waf1), tob). Markedly down-regulated genes included members of the Id
      family genes (dominant negative regulators of basic helix-loop-helix
      transcription factors), and cytoplasmic dynein light chain and apoptosis-related
      gene NIP3. These alterations in the expression profile induce a transient heat
      shock gene response and activation of genes involved in growth arrest and
      cellular adaptation and/or differentiation.

PMID- 12183055
TI  - Involvement of mitogen protein kinase cascade in agonist-mediated human A(3)
      adenosine receptor regulation.
AB  - It has been suggested that A(3) adenosine receptors (ARs) play a role in the
      pathophysiology of cerebral ischemia with dual and opposite neuroprotective and
      neurodegenerative effects. This could be due to a receptor regulation mediated by
      rapid phosphorylation and desensitization carried out by intracellular kinases.
      In this study, we investigated the involvement of extracellular regulated kinase
      (ERK 1 and 2), members of the mitogen-activated protein kinase (MAPK) family, in
      A(3) AR phosphorylation. A(3) AR mediated the activation of ERK 1/2 with a
      typical transient monophasic kinetics (5 min). The activation was not affected by
      hypertonic sucrose cell pre-treatment, suggesting that this effect occurred
      independently of receptor internalization. The involvement of MAPK cascade in the
      A(3) AR regulation process was evaluated using two well-characterized MAPK kinase
      inhibitors, PD98059 (2-(2'-amino-3'-methoxyphenyl)oxanaphthalen-4-one) and U0126
      (1,4-diamino-2,3-dicyano-1,4-bis (aminophenylthio) butadiene). The exposure of
      cells to PD98059 prevented MAPK activation and inhibited homologous A(3) AR
      desensitization and internalization, impairing agonist-mediated receptor
      phosphorylation. PD98059 inhibited the membrane translocation of G protein
      coupled receptor kinase (GRK(2)), which is involved in A(3) AR homologous
      phosphorylation, suggesting this kinase as a target for the MAPK cascade. On the
      contrary, the chemically unrelated inhibitor of the MAPK cascade, U0126, did not
      significantly affect GRK(2) membrane translocation or receptor internalization.
      Nevertheless, the inhibitor induced a significant impairment of receptor
      phosphorylation and desensitization. These results suggested that the MAPK
      cascade is involved in A(3) AR regulation by a feedback mechanism which controls
      GRK(2) activity and probably involves a direct receptor phosphorylation.

PMID- 12183056
TI  - MacroH2A1.2 binds the nuclear protein Spop.
AB  - X-chromosome inactivation is a phenomenon by which one of the two X chromosomes
      in somatic cells of female mammals is inactivated for life. The inactivated X
      chromosomes are covered with Xist (X-inactive specific transcript) RNA, and also
      enriched with the histone H2A variant, macroH2A1.2. The N-terminal one-third of
      macroH2A1.2 is homologous to core histone H2A, but the function of the C-terminal
      two-thirds, which contains a basic, putative leucine zipper domain, remains
      unknown. In this study, we tried analyzing protein-protein interaction with a
      yeast two-hybrid system to interact with the nonhistone region of mouse
      macroH2A1.2. The results showed that macroH2A1.2 interacts with mouse nuclear
      speckled type protein Spop. The Spop protein has a unique composition: an N
      terminal MATH, and a C-terminal BTB/POZ domain. Further binding domain mapping in
      a glutathione-S-transferase (GST) pull-down experiment revealed that macroH2A1.2
      binds the MATH domain of Spop, which in turn binds to the putative leucine zipper
      domain of macroH2A1.2.

PMID- 12183057
TI  - Extracellular signal-regulated kinases 1 and 2 participate in interleukin-17 plus
      tumor necrosis factor-alpha-induced stabilization of interleukin-6 mRNA in human
      pancreatic myofibroblasts.
AB  - In human pancreatic myofibroblasts, interleukin (IL)-17 markedly enhances tumor
      necrosis factor (TNF)-alpha-induced IL-6 secretion through the induction of IL-6
      mRNA stabilization. Induced stability of IL-6 mRNA was markedly decreased by the
      inhibitors of extracellular signal-regulated kinase (ERKs), PD98059 and U0216.
      This indicates that activation of the ERK pathway is involved in the induction of
      IL-6 mRNA stabilization by IL-17 plus TNF-alpha.

PMID- 12183058
TI  - Translocation of pyrene-labeled phosphatidylserine from the plasma membrane to
      mitochondria diminishes systematically with molecular hydrophobicity:
      implications on the maintenance of high phosphatidylserine content in the inner
      leaflet of the plasma membrane.
AB  - To study the translocation of phosphatidylserine (PS) from plasma membrane to
      mitochondria, dipyrene PS molecules (diPyr(n)PS; n=acyl chain length) were
      introduced to the plasma membrane of baby hamster kidney cells (BHK cells) using
      either cyclodextrin-mediated monomer transfer or fusion of cationic vesicles.
      Translocation of diPyr(n)PS to mitochondria was assessed based on decarboxylation
      by mitochondrial PS decarboxylase (PSD). It was found that the rate of
      translocation diminishes systematically with acyl chain length (molecular
      hydrophobicity) of diPyr(n)PS. Using an in vitro assay, it was shown that the
      spontaneous translocation rates of long-chain diPyr(n)PS species are similar to
      those of common natural PS species, thus supporting the biological relevance of
      the data. These results, and other data arguing against the involvement of
      vesicular traffic and lipid transfer proteins, imply that spontaneous monomeric
      diffusion via the cytoplasm is the main mechanism of PS movement from the plasma
      membrane to mitochondria. This finding could explain why a major fraction of PS
      synthesized by BHK cells consists of hydrophobic species: such species have
      little tendency to efflux from the plasma membrane to mitochondria where they
      would be decarboxylated. Thus, adequate molecular hydrophobicity seems to be
      crucial for the maintenance of high PS content in the inner leaflet of the plasma
      membrane.

PMID- 12183059
TI  - Targeting of peptides to restenotic vascular smooth muscle cells using phage
      display in vitro and in vivo.
AB  - Restenosis after angioplasty occurs in 30-40% of the treated patients. To develop
      a strategy to deliver drugs to restenotic lesions, we selected phages that bind
      to proliferating vascular smooth muscle cells (VSMC), from a random constraint 15
      mer peptide phage display library. Phages were selected for binding to cultured
      primary aortic VSMC (in vitro biopanning) and selected for binding to denudated
      carotid arteries in mice (in vivo biopanning). In vitro biopanning did not result
      in a consensus sequence, but recurring FLGW and LASR amino acid motifs were
      identified. In vivo biopanning resulted in two consensus peptides 5G6
      (CNIWGVVLSWIGVFPEC) and 5E5 (CESLWGGLMWTIGLSDC). Surprisingly, these two
      sequences were recovered after both in vitro and in vivo biopanning, but
      predominantly in vivo. Moreover, a strong recurring motif, IGR, was identified in
      the in vivo clones. The consensus phages 5G6 and 5E5 bind selectively to VSMC
      compared to other cell types. Furthermore, they bind preferentially to
      proliferating VSMC compared to VSMC that were growth arrested, and are
      effectively internalized by their target cells. The specific binding capacities
      of 5G6 and 5E5 phages suggest that these peptide sequences can be used for
      targeting of restenotic lesions, in which proliferating VSMC are the dominant
      cell type.

PMID- 12183060
TI  - Urokinase is required for the formation of mactinin, an alpha-actinin fragment
      that promotes monocyte/macrophage maturation.
AB  - We have previously shown that lysates from HL-60 myeloid leukemia cells or from
      peripheral blood monocytes are able to degrade alpha-actinin to form a 31-kDa
      amino-terminal fragment with monocyte/macrophage maturation promoting activity.
      In contrast, intact alpha-actinin, which is a 100-kDa actin-binding protein, has
      no differentiating activity. The aim of this study was to investigate the enzyme
      responsible for the degradation of alpha-actinin to form this fragment, named
      mactinin. The ability of cell lysates to degrade [125I]alpha-actinin in the
      presence of various enzyme inhibitors, including inhibitors of
      metalloproteinases, cysteine proteinases, and serine proteases, was measured.
      Phenylmethylsulfonyl fluoride (PMSF) was the only inhibitor able to prevent
      formation of mactinin by cell lysate degradation of alpha-actinin, suggesting
      that a serine protease is responsible for the digestion. Of the various serine
      proteases tested (thrombin, plasmin, and urokinase), only urokinase was able to
      produce a 31-kDa band. The urokinase-generated 31-kDa band promoted maturation in
      HL-60 cells. Amiloride, a specific inhibitor of urokinase, inhibited production
      of the 31-kDa alpha-actinin fragment by HL-60 cell lysates. For in vivo tests,
      inflammatory fluid (from bronchoalvelolar lavage) was collected from uPA
      (urokinase) knockout mice and their wild-type counterparts after intratracheal
      challenge with Pneumocystis carinii. Although most (6 of 8) wild-type mice had
      mactinin in their inflammatory fluid samples, none (0 of 8) of the uPA knockout
      mice had mactinin present (P<0.01). These results demonstrate that urokinase is
      necessary and sufficient for the formation of the monocyte/macrophage maturation
      promoting fragment, mactinin, in vitro and in vivo. These findings support the
      role of urokinase in the regulation of monocyte/macrophage functions, such as
      that occurring in inflammatory reactions.

PMID- 12183062
TI  - A cyclin-dependent protein kinase homologue associated with the basal body
      domains in the ciliate Tetrahymena thermophila.
AB  - The tight coupling between cell cycle progression and morphogenetic development
      in the unicellular ciliates presents a unique model system for examination of the
      roles of Cdks in developmental processes. We here describe the isolation and
      characterization of the first cyclin-dependent kinase (Cdk) homologue, TtCdk1,
      from Tetrahymena thermophila. TtCdk1 corresponds to the larger of the two
      polypeptides recognized by anti-PSTAIRE antibody in a whole cell lysate, which
      differ from each other in their affinity for yeast p13(suc1) protein. In contrast
      to the constant protein expression levels of typical eukaryotic Cdks, the TtCdk1
      protein level fluctuates periodically over the vegetative cell cycle, reaching a
      maximum at the end of the cell cycle, correlating with its histone H1 kinase
      activity. Its association with the membrane-skeletal domains that surround
      mature, but not nascent, basal bodies in the cell cortex suggests that TtCdk1
      plays a role in the regulation of cortical morphogenesis in T. thermophila. A
      partial TtCDK1 knockout cell line constructed through somatic biolistic
      transformation resulted in a reduction of the regularity of the rows of basal
      bodies plus an additional effect on chromatin condensation in both macro- and
      micronuclei. Unlike the situations in higher eukaryotic cells, no apparent effect
      on basal body duplication was found upon disruption of the TtCDK1 gene.

PMID- 12183061
TI  - Therapeutic efficacy of anti-ErbB2 immunoliposomes targeted by a phage antibody
      selected for cellular endocytosis.
AB  - Many targeted cancer therapies require endocytosis of the targeting molecule and
      delivery of the therapeutic agent to the interior of the tumor cell. To generate
      single chain Fv (scFv) antibodies capable of triggering receptor-mediated
      endocytosis, we previously developed a method to directly select phage antibodies
      for internalization by recovering infectious phage from the cytoplasm of the
      target cell. Using this methodology, we reported the selection of a panel of scFv
      that were internalized into breast cancer cells from a nonimmune phage library.
      For this work, an immunotherapeutic was generated from one of these scFv (F5),
      which bound to ErbB2 (HER2/neu). The F5 scFv was reengineered with a C-terminal
      cysteine, expressed at high levels in Escherichia coli, and coupled to sterically
      stabilized liposomes. F5 anti-ErbB2 immunoliposomes were immunoreactive as
      determined by surface plasmon resonance (SPR) and were avidly internalized by
      ErbB2-expressing tumor cell lines in proportion to the levels of ErbB2
      expression. F5-scFv targeted liposomes containing doxorubicin had antitumor
      activity and produced significant reduction in tumor size in xenografted mice
      compared to nontargeted liposomes containing doxorubicin. This strategy should be
      applicable to generate immunotherapeutics for other malignancies by selecting
      phage antibodies for internalization into other tumor types and using the scFv to
      target liposomes or other nanoparticles.

PMID- 12183063
TI  - Glutathione oxidation in calcium- and p38 MAPK-dependent membrane blebbing of
      endothelial cells.
AB  - Under conditions where apoptosis is prevented, peroxides disrupt the endothelial
      monolayer by inducing cytoskeletal rearrangements, cell retraction and formation
      of arrays of membrane blebs. In human umbilical vein endothelial cells (HUVEC),
      the H(2)O(2)-induced membrane blebbing was found to be a transient process
      executed by two parallel signaling mechanisms: (i) mobilization of cytosolic
      [Ca(2+)](i) through a pathway requiring oxidation of reduced glutathione (GSH),
      and (ii) activation of p38 mitogen-activated protein kinases (MAPK) independently
      of GSH oxidation and Ca(2+) mobilization. In the HUVEC, membrane blebbing was
      thus blocked by inhibition of GSH oxidation, Ca(2+) mobilization or p38 MAPK
      activation. Stimulation of GSH peroxidation with ebselen potentiated the H(2)O(2)
      induced oscillating Ca(2+) response and the bleb formation, but not p38
      phosphorylation. Chelation of [Ca(2+)](i) abolished the blebbing process but not
      p38 activation. In addition, in the GSH peroxidase-resistant cell line ECV304,
      H(2)O(2) was unable to promote membrane blebbing or significant Ca(2+) release,
      while p38 became phosphorylated. However, [Ca(2+)](i) was increased and blebs
      were formed, when the ECV304 were treated with ebselen before H(2)O(2). Together,
      this leads to a model where oxidative stress, through both Ca(2+)-dependent and
      p38 kinase-mediated phosphorylation events, causes reassembly of the actin
      cytoskeleton and subsequent appearance of membrane blebs at the plasma membrane.

PMID- 12183064
TI  - Protein and thiol oxidation in cells exposed to peroxyl radicals is inhibited by
      the macrophage synthesised pterin 7,8-dihydroneopterin.
AB  - Monocyte cells are exposed to a range of reactive oxygen species (ROS) when they
      are recruited to a site of inflammation. In this study, we have examined the
      damage caused to the monocyte-like cell line U937 by peroxyl radicals and
      characterised the protective effect of the macrophage synthesised compound 7,8
      dihydroneopterin. Exposure of U937 cells to peroxyl radicals, generated by the
      thermolytic breakdown of 2,2'-azobis(amidinopropane) dihydrochloride (AAPH),
      resulted in the loss of cell viability as measured by thiazolyl blue (MTT)
      reduction, and lactate dehydrogenase (LDH) leakage. The major form of cellular
      damage observed was cellular thiol loss and the formation of reactive protein
      hydroperoxides. Peroxyl radical oxidation of the cells only caused a small
      increase in cellular lipid oxidation measured. Supplementation of the media with
      increasing concentrations of 7,8-dihydroneopterin significantly reduced the
      cellular thiol loss and inhibited the formation of the protein hydroperoxides.
      High performance liquid chromatography (HPLC) analysis showed 7,8
      dihydroneopterin was oxidised by both peroxyl radicals and preformed protein
      hydroperoxides to predominately 7,8-dihydroxanthopterin. The possibility that 7,8
      dihydroneopterin is a cellular antioxidant protecting macrophage proteins during
      inflammation is discussed.

PMID- 12183065
TI  - Volatile organic compounds cytotoxicity and expression of HSP72, HSP90 and GRP78
      stress proteins in cultured human cells.
AB  - The aim of this study was to determine whether overexpression of stress proteins
      (SPs) could be a sensitive biomarker for cell injury due to exposure to low doses
      of volatile organic compounds (VOCs) such as benzene, ethylbenzene, toluene,
      xylene, and chlorinated derivatives (ClB). Sublethal and cytotoxic threshold
      concentrations of the VOCs were determined by studying the growth rate of normal
      (fibroblasts) or tumor-derived human cell lines (A549, HepG2) exposed for 4 days
      to VOCs. Changes in SP expression as a function of concentrations were
      investigated by Western blotting.VOC toxicity was found to be correlated with
      their degree of chlorination and their hydrophobicity. Cytotoxic threshold
      concentrations (no-observed effect concentration, NOEC) were found to be similar
      for the three cell lines. It was observed that using a mixture of VOCs, each of
      them at concentration below the NOEC, resulted in an actual toxicity to the
      cells. This finding reveals a synergistic effect and should be taken into account
      when assessing threshold risk and exposure limit values in the worker's
      environment when several pollutants may be present. HSP72 and HSP90 expression
      levels were not affected whereas GRP78 expression was increased by all the VOCs.
      Taking into account the specific molecular function of GRP78, it suggests that
      VOC exposure results in misfolded or underglycosylated protein accumulation in
      the endoplasmic reticulum. GRP78 overexpression was closely related to the
      magnitude of growth inhibition due to increasing concentrations of each VOC. The
      overexpression was found to be significant for concentrations 5 to 30 times
      higher than NOEC, indicating that, under our experimental conditions, GRP78
      expression cannot be considered as a sensitive biomarker of exposure to
      environmental VOCs.

PMID- 12183066
TI  - Import of assembled PTS1 proteins into peroxisomes of the yeast Hansenula
      polymorpha: yes and no!
AB  - Previously, Waterham et al. [EMBO J. 12 (1993) 4785] reported that cytosolic
      oligomeric alcohol oxidase (AO) is not incorporated into peroxisomes after
      reassembly of the organelles in the temperature-sensitive peroxisome-deficient
      mutant pex1-6(ts) of Hansenula polymorpha shifted to permissive growth
      conditions. Here, we show that the failure to import assembled AO protein is not
      exemplary for other folded proteins because both an artificial peroxisomal matrix
      protein, PTS1-tagged GFP (GFP.SKL), and the endogenous dimeric PTS1 protein
      dihydroxyacetone synthase (DHAS) were imported under identical conditions. In
      vitro receptor-ligand binding studies using immobilised H. polymorpha Pex5p and
      crude extracts of methanol-induced pex1-6(ts) cells, showed that AO octamers did
      not interact with the recombinant PTS1 receptor, at conditions that allowed
      binding of folded GFP.SKL and dimeric DHAS. This shows that import of oligomeric
      proteins is not a universal pathway for peroxisomal matrix proteins.

PMID- 12183067
TI  - Overexpression of chemokine-like factor 2 promotes the proliferation and survival
      of C2C12 skeletal muscle cells.
AB  - Chemokine-like factor 1 (CKLF1) is a novel cytokine first cloned from U937 cells.
      It contains different splicing forms and has chemotactic effects on a wide
      spectrum of cells both in vitro and in vivo; it can also stimulate the
      regeneration of skeletal muscle cells in vivo, but the mechanism remains unclear.
      To probe the myogenesis function of CKLF2, which is the largest isoform of CKLFs,
      C2C12 murine myoblasts were stably transfected with human CKLF2 eukaryotic
      expression vector. Compared with control vector transfected C2C12 cells, CKLF2
      overexpression causes accelerated myoblast proliferation as determined by cell
      counting and [(3)H]TdR incorporation assays. In addition, CKLF2 overexpression
      also promotes cell differentiation, which was determined by higher expression
      levels of myogenin, creatine kinase, myosin and the accelerated myoblast fusion.
      Further analysis also indicates that CKLF2 could activate the transcription
      activity of the bHLH/MyoD and MEF2 families. Finally, DNA synthesis and myotube
      formation could also be promoted by growing C2C12 cells in conditioned media from
      CKLF2-transfected cells. These findings strongly suggest a role for human CKLF2
      in regulation of skeletal muscle myogenesis.

PMID- 12183068
TI  - ABCG4: a novel human white family ABC-transporter expressed in the brain and eye.
AB  - White family transporters are a group of ATP-binding cassette (ABC) proteins that
      show sequence homology to the Drosophila white gene product. The Drosophila
      protein is a subunit of heterodimeric transporters of precursors for eye-pigment
      synthesis. A novel, human member of this family (ABCG4) has been identified.
      Northern blotting shows that ABCG4 is expressed specifically in the brain and the
      eye.

PMID- 12183069
TI  - Anticoagulants in cancer treatment: malignancy as a solid phase coagulopathy.
AB  - The purpose of this review is to demonstrate the potential for development of
      coagulation-reactive drugs for experimental cancer treatment. Improved cancer
      outcome has been reported in several tumor types with drugs that interfere with
      thrombin-generating or urokinase-initiated pathways expressed by tumor cells.
      These pathways participate in the response to injury and their inappropriate
      expression by malignant cells supports tumor growth. A proposed classification of
      tumor types based on the differential occurrence of these pathways may account
      for variation in drug responsiveness and guide clinical trial design. Among drugs
      available for testing, aprotinin and low molecular weight heparin have particular
      appeal. The former blocks a pathway of tumor cell growth, invasion and metastasis
      while the latter blocks growth factor activity, angiogenesis, and other tumor
      growth mechanisms as well as coagulation activation. Conceiving of malignancy as
      a solid phase coagulopathy may facilitate development of effective but non-toxic
      cancer treatments and encourage inquiry into the putative 'injury' responsible
      for both coagulation activation and carcinogenesis.

PMID- 12183070
TI  - Dietary genistein suppresses chemically induced prostate cancer in Lobund-Wistar
      rats.
AB  - Epidemiological reports suggest that Asians consuming a diet high in soy have a
      low incidence of clinically manifested prostate cancer. We have tested the
      hypothesis that life-time exposure to genistein, the primary isoflavone component
      of soy, is responsible for this protective effect. Lobund-Wistar rats were
      exposed to 0, 25 and 250 mg genistein/kg AIN-76A diet, starting at conception and
      continued until necropsy at 11 months. Male offspring were injected s.c. with
      Flutamide on days 50-66 and with testosterone on days 67-69, injected with N
      methylnitrosourea (NMU) into the dorsal prostate on day 70, and given
      testosterone implants, starting at day 77. Genistein in the diet inhibited the
      development of NMU-induced prostate invasive adenocarcinomas, in a dose-dependent
      manner. Genistein did not alter body, prostate and testes weights. Male rats fed
      0, 25 and 250 mg genistein/kg diet had serum genistein concentrations of 9, 60
      and 861 pmol/ml, and prostate genistein concentrations of 85, 230 and 775 pmol/g
      tissue. We conclude that lifetime dietary genistein protected against chemically
      induced prostate cancer development in rats.

PMID- 12183071
TI  - The combination of 1alpha,25(OH2)-vitamin D3, calcium and acetylsalicylic acid
      affects azoxymethane-induced aberrant crypt foci and colorectal tumours in rats.
AB  - Effects of 1alpha,25(OH)(2)-vitamin D(3) and acetylsalicylic acid at various
      dietary levels of calcium (CaCO(3)) on development of aberrant crypt foci (ACF)
      and tumours in colon were examined in groups of 16 male F344 rats initiated with
      azoxymethane and observed for 16 weeks. Calcium was the most potent modulator of
      ACF development. The total number of ACF increased with low calcium and decreased
      with high calcium. The number of large ACF decreased with any addition of
      calcium, acetylsalicylic acid and 1alpha,25(OH)(2)-vitamin D(3). High levels of
      calcium alone or in combination with 1alpha,25(OH)(2)-vitamin D(3) increased the
      incidence of tumour-bearing animals. 1alpha,25(OH)(2)-vitamin D(3) and
      acetylsalicylic acid at 5,000 ppm calcium increased the incidence as well.

PMID- 12183072
TI  - Oncogenic ras alters sensitivity of mouse colonocytes to butyrate and fatty acid
      mediated growth arrest and apoptosis.
AB  - Docosahexaenoic acid (DHA) and butyrate favorably modulate colonocyte
      proliferation and apoptosis. In order to elucidate how oncogenic Ras modulates
      responses to these chemopreventive nutrients, we incubated isogenic non
      transformed and Ras malignant transformed mouse colon cells with butyrate and DHA
      or linoleic acid (LA). Combining DHA with 1mM butyrate decreased proliferation
      relative to LA or no PUFA treatment in both cell lines. At a higher butyrate dose
      (5mM), caspase 3 activity was elevated to a greater extent in Ras transformed
      cells. Only non-transformed cells were sensitive to the apoptogenic effects of
      DHA, indicating that Ras transformation alters sensitivity to dietary
      chemopreventive agents.

PMID- 12183073
TI  - Inhibitory effect of stabilized analogues of glycoglycerolipids on Epstein-Barr
      virus activation and mouse skin tumor promotion.
AB  - Nine new synthetic compounds, structurally related to the most active
      glycoglycerolipid analogues carrying a hexanoyl chain, were tested for their anti
      tumor-promoting activity using a short-term in vitro assay for Epstein-Barr virus
      (EBV) activation. All these compounds, in which the ester function is replaced by
      different metabolically more stable groups, were almost as active as their ester
      reference compounds in inhibiting the EBV activation promoted by the tumor
      promoter 12-O-tetradecanoylphorbol-13-acetate (TPA). Two of these, devoid of any
      functionality on the lipophilic chain, when tested in an in vivo two-stage
      carcinogenesis test, exhibited marked inhibitory effects on mouse skin tumor
      promotion.

PMID- 12183074
TI  - Dietary soy modulation of biochemical parameters in DMBA-induced mammary tumors.
AB  - The aim of this study was to extend our previous observations on the soy
      modulation of biochemical parameters in 7,12-dimethylbenz[a]anthracene (DMBA)
      induced rat mammary tumors, by simultaneously investigating the expression of
      estrogen receptor-alpha (ERalpha), estrogen receptor-beta (ERbeta), progesterone
      receptor (PR), apoptosis, neu, and markers of cell proliferation, such as
      proliferating cell nuclear antigen (PCNA) by immunohistochemistry. The percentage
      of ERalpha positive tumors was 65.8% in masses from control animals, and
      significantly dropped to 36.8% in tumors from soy treated rats (P=0.010). The
      percentage of ERbeta positive tumors was 70.3% in masses from control animals vs.
      50.0% in tumors from soy exposed animals (P=0.066). Moreover, the percentage of
      cases which were both ERalpha and ERbeta positive was significantly lower (17.6%)
      in soy treated than in control animals (51.3%) (P=0.006). The percentage of PR
      positive tumors was 34.2% in control animals vs. 2.6% in tumors from soy treated
      rats (P=0.0006). There were no statistically significant differences in the
      percentage of tumors positively stained for neu, apoptosis, or PCNA, in control
      vs. soy treated rats. However, when analyzing the reciprocal correlation among
      the different biochemical parameters we showed that, in treated animals, the
      majority of ERalpha positive tumors (91.7%) were also PCNA positive (P=0.036).
      The median percentage of PCNA positivity was significantly higher in ERalpha
      positive than in ERalpha negative tumors (25 vs. 5%) (P=0.0031). Moreover, an
      association was found between PCNA and neu status since all neu positive tumors
      were also PCNA positive (P=0.011).

PMID- 12183075
TI  - Mutation analyses of the NFAT1 gene in chondrosarcomas and enchondromas.
AB  - Mice lacking nuclear factor of activated T cell 1 (NFAT1) showed an abnormal
      proliferation of chondrocytes in articular cartilage and formed an extraosseous
      cartilaginous mass resembling a neoplastic lesion, suggesting that the NFAT1 gene
      is a tumor suppressor gene in cartilaginous neoplasms. Here we performed mutation
      analyses of the NFAT1 gene in human cartilaginous tumors including 30
      chondrosarcomas and 15 enchondromas. Reverse transcription-polymerase chain
      reaction (PCR) analysis revealed the expression of the NFAT1 gene in 15/15
      chondrosarcomas and 12/13 enchondromas. To find subtle alterations, the genomic
      structure of the NFAT1 gene was determined using human genome draft sequences,
      and a mutation analysis was performed using the exon-by-exon PCR-single-strand
      conformation polymorphism method. Two heterozygous missense mutations, A1557T
      (His446Leu) and C2859T (Pro880Leu), were found in eight tumor samples, but the
      same mutation was also present in the constitutional cells of corresponding
      patients. The incidence of the mutant alleles in the patient and control groups
      showed no significant difference, suggesting that these mutations are rare single
      nucleotide polymorphisms unrelated with tumorigenesis. These results suggest that
      the NFAT1 gene is not likely to be a tumor suppressor gene in human cartilaginous
      tumors.

PMID- 12183076
TI  - Combined hypermethylation and chromosome loss associated with inactivation of SSI
      1/SOCS-1/JAB gene in human hepatocellular carcinomas.
AB  - We previously demonstrated using restriction landmark genomic scanning-based 2
      dimensional genome electrophoresis method decreased results of 16 primary
      hepatocellular carcinomas (HCCs) revealed reduction of intensity of 60 NotI
      landmark spots, and increase in five spots that were frequently observed in HCCs.
      Most frequently decreased spot (14/16 HCCs) was identified to it corresponds to a
      gene encoding SSI-1, a JAK-binding protein (SSI-1/SOCS-1/JAB) that regulated the
      JAK/STAT signal transduction pathway. This signaling pathway is important for
      relaying signals from various cytokines outside the cell to the inside.
      Expression level of SOCS-1 messenger RNA was markedly suppressed in 50% of HCCs
      (4/8). Loss of heterozygosity at the SSI-1 gene, was found in all cases with
      aberrant expression. Methylation analysis of the CpG-rich regions of SSI-1 gene
      revealed hypermethylation of these regions. In an additional series of
      methylation analysis using 30 HCCs, 16 (53%) showed hypermethylation of the gene.
      These results indicate that the SSI-1 gene is silenced in a substantial portion
      of HCC though the combined mechanisms of methylation of either 5' or exon CpG
      rich regions and by a chromosomal loss of the remaining allele.

PMID- 12183077
TI  - Involvement of diverse protein kinase C isoforms in the differentiation of ML-1
      human myeloblastic leukemia cells induced by the vitamin D3 analogue KH1060 and
      the phorbol ester TPA.
AB  - We reported previously that diverse combination of the vitamin D(3) analogue
      KH1060 together with 12-O-tetradecanoylphorbol-13-acetate (TPA) synergistically
      induces the differentiation of ML-1 cells into mature macrophages. To investigate
      the mechanism involved in their interaction, we examined the role of protein
      kinase C (PKC) in the differentiation of ML-1 cells to mature macrophages. We
      found that the specific PKC inhibitor GF109203 suppressed the morphological
      change and the alpha-naphthyl acetate esterase activity induced in ML-1 cells by
      treatment with KH1060 plus TPA. This treatment increased the translocation of PKC
      alpha, PKC epsilon, and PKC theta from cytosol to membranes. ML-1 cells treated
      with KH1060 alone increased translocation of PKC theta, whereas cells treated
      with TPA alone increased translocation of PKC alpha and PKC epsilon. These data
      showed that in human myeloblastic leukemia cells, diverse isoforms of PKC,
      including PKC alpha, epsilon, and theta, participate in the regulation of cell
      differentiation.

PMID- 12183078
TI  - Wnt-7a is upregulated by norethisterone in human endometrial epithelial cells: a
      possible mechanism by which progestogens reduce the risk of estrogen-induced
      endometrial neoplasia.
AB  - Progestogens are added to oestrogen in hormone replacement therapy regimens to
      reduce the risk of endometrial cancer. We have performed in vitro studies
      analysing gene expression of isolated normal endometrial epithelia cells (NEE)
      treated with estradiol and the progestogen norethisterone acetate (NETA). We
      report here for the first time upregulation of the Wnt-7a gene by NETA in
      estrogen treated NEE. Wnt genes are a large family of developmental genes
      associated with cellular responses such as oncogenesis. We therefore suggest that
      upregulation of Wnt-7a may be associated with the antineoplastic effects of
      progestogens on the endometrium.

PMID- 12183079
TI  - Asiatic acid, a triterpene, induces apoptosis through intracellular Ca2+ release
      and enhanced expression of p53 in HepG2 human hepatoma cells.
AB  - Asiatic acid (AA), a triterpene, decreased viability and induced apoptosis of
      HepG2 human hepatoma cells in a dose-dependent manner. AA also markedly increased
      intracellular Ca(2+) level, which was blocked by TMB-8 and dantrolene,
      intracellular Ca(2+) release blockers, but not by EGTA, an extracellular Ca(2+)
      chelator. Moreover, AA-induced apoptosis was significantly suppressed by
      treatment with TMB-8 and dantrolene, suggesting that intracellular Ca(2+) release
      may play an essential role in the AA-induced apoptosis. In addition, AA
      profoundly increased protein level of p53, which was also inhibited by BAPTA/AM,
      an intracellular Ca(2+) chelator, TMB-8 and dantrolene. Treatment with A23187, a
      Ca(2+) ionophore, or thapsigargin, a Ca(2+)-ATPase inhibitor, alone enhanced p53
      nuclear accumulation, indicating that p53 accumulation is dependent on
      intracellular Ca(2+) increase. Furthermore, the viability of Hep3B, p53-null
      cells, was much higher than that of HepG2, p53-wild type cells, when treated with
      AA. Taken together, these results suggest that AA induced apoptosis through
      increased intracellular Ca(2+), which, in turn, enhanced p53 expression in HepG2
      cells. These results further suggest that AA may be a valuable agent for the
      therapeutic intervention of human hepatomas.

PMID- 12183080
TI  - Induction of telomerase activity during an early burst of proliferation in
      pancreatic regeneration.
AB  - Telomerase activity (TA) and telomerase reverse transcriptase (rTERT) were
      investigated in Sprague-Dawley rats, killed at 6 and 12 h, and 1, 2, 3, 7, and 14
      days after 90% pancreatectomy (px), by TRAPeze enzyme-linked immunosorbent assay
      telomerase detection and reverse transcriptase-polymerase chain reaction. TA
      increased at 2 days and reached a maximum at 3 days after px, when the small
      ductules showed the highest proliferation activity. After 3 days, TA decreased to
      basal levels as the ductules differentiated into new endocrine and exocrine
      pancreas. The expression of rTERT showed a correlation with TA. These results
      suggest telomerase is actively regulated during pancreatic regeneration.

PMID- 12183081
TI  - Expression and activity of potassium ion channels in human prostate cancer.
AB  - Four normal and 79 human prostate cancer (Pca) specimens were examined, by
      immunohistochemistry, for expression of voltage-gated potassium ion channels.
      Strong immunostaining (for Kv1.3) was observed in the normal and 47% (37/79) of
      Pca specimens. Twenty-nine percent (23/79) Pca specimens showed moderate and 24%
      (19/79) displayed low staining. Three potassium channel-openers at a
      concentration of 10 microg/mL, minoxidil (47.8 microM), 1-Ethyl-2
      benzimidazolinone (EBIO) (61.7 microM) and diazoxide (43.3 microM), increased
      growth of PC3 cells by 30-50%. Potassium channel-blockers, dequalinium,
      amiodarone and glibenclamide, caused a dose-dependent, growth inhibition of four
      human Pca cell lines. Apoptosis occurred within 4h of treatment of PC3 cells with
      dequalinium (0.5 microg/mL, 0.9 microM), amiodarone (5 microg/mL, 7.3 microM) or
      glibenclamide (50 microg/mL, 0.1mM).

PMID- 12183083
TI  - Expression of p27(Kip1) in bladder cancers: immunohistochemical study and
      prognostic value in a series of 95 cases.
AB  - Prognostic value of p27(Kip1) immunohistochemical expression was evaluated in a
      series of 95 bladder carcinomas. Low p27(Kip1) expression was correlated with
      higher tumor grade (P=0.01) and stage (P=0.009), associated with poor overall
      survival (P=0.01) and, for superficial cancers, with disease-free survival
      (P=0.05). Thirty-five cases exhibited a heterogeneous expression related in some
      instances to tumoral architecture. Seventeen cases showed a cytoplasmic
      reactivity related to low nuclear expression (P=0.057). Loss of p27(Kip1)
      expression is a pejorative event in bladder tumors and inhibition of p27(Kip1)
      degradation could offer new therapeutic ways.

PMID- 12183082
TI  - MDR1 gene expression in hepatocellular carcinoma and the peritumoral liver of
      patients with and without cirrhosis.
AB  - P-glycoprotein (P-gp) and MDR1 mRNA expressions were assessed in tumoral and
      peritumoral specimens from patients with hepatocellular carcinoma (HCC) and in
      cirrhotic livers without HCC, using immunohistochemistry (C494 monoclonal
      antibody) and reverse transcription-polymerase chain reaction (RT-PCR) analysis.
      P-gp overexpression was detected in 24/28 tumoral livers (85%). In the
      peritumoral liver, staining was strong in cirrhotic nodules, and fainter in non
      cirrhotic specimens. P-gp expression was as intense in the cirrhotic specimens
      free of HCC as in the peritumoral tissue of HCC developing in cirrhotic patients.
      These results were confirmed by RT-PCR analysis.

PMID- 12183084
TI  - Preliminary in vivo experimental evidence on intratumoral morphine uptake.
      Possible clinical implications in cancer pain and opioid responsiveness.

PMID- 12183085
TI  - Block of interdigital nerves for cancer pain.

PMID- 12183086
TI  - A dramatic response to inhaled cannabis in a woman with central thalamic pain and
      dystonia.

PMID- 12183088
TI  - Analgesia with ketamine in a patient with perioperative opioid tolerance.

PMID- 12183087
TI  - Dexmedetomidine: a new option for intractable distress in the dying.

PMID- 12183089
TI  - Botulinum toxin for severe anorectal pain.

PMID- 12183090
TI  - German medical education in pain therapy and palliative medicine: a comparison of
      British, Canadian, and United States models.

PMID- 12183091
TI  - Re: systematic review of spinal manipulation.

PMID- 12183092
TI  - A measure of the quality of dying and death. Initial validation using after-death
      interviews with family members.
AB  - A reliable and valid measure of the quality of the dying experience would help
      clinicians and researchers improve care for dying patients. To describe the
      validity of an instrument assessing the quality of dying and death using the
      perspective of family members after death and to identify clinical correlates of
      a high quality death, a retrospective cohort study evaluated the 31-item Quality
      of Dying and Death (QODD) questionnaire. The questionnaire was administered to
      family members of patients who died in Missoula county Montana in 1996 and 1997.
      The interview included questions assessing symptoms, patient preferences, and
      satisfaction with care. Measurement validity was examined for item and total
      scores and reliability analyses for the QODD total score were assessed. Construct
      validity was assessed using measures of concepts hypothesized to be associated
      with the quality of dying and death. There were 935 deaths, of which 252 (27.0%)
      family interviews were represented. Non-enrolled decedents were not significantly
      different from enrolled decedents on age, sex, cause of death, or location of
      death. We excluded sudden deaths (n = 45) and decedents under age 18 (n = 2),
      leaving 205 after-death interviews. A total QODD score, on a scale from 0 to 100
      with higher scores indicating better quality, ranged from 26.0 to 99.6, with a
      mean of 67.4 and Cronbach's alpha of 0.89. The total QODD score was not
      associated with patient age, sex, education, marital status, or income. As
      hypothesized, higher QODD scores were significantly associated with death at home
      (P < 0.01), death in the location the patient desired (P < 0.01), lower symptom
      burden (P < 0.001), and better ratings of symptom treatment (P< 0.01). Although
      the total score was not associated with the presence of an advance directive,
      higher scores were associated with communication about treatment preferences (P <
      0.01), compliance with treatment preferences (P < 0.001), and family satisfaction
      regarding communication with the health care team (P < 0.01). Availability of a
      health care team member at night or on weekends was also associated with a higher
      QODD score (P < 0.001). The QODD total score demonstrated good cross-sectional
      validity. Clinicians caring for dying patients should focus on improving
      communication with the patient and family and improving symptom assessment and
      treatment. Health care teams should focus on continuity of care, including having
      a team member familiar with the patient available for calls at nights and on
      weekends. Future work will assess the potential role of the QODD in improving the
      quality of the dying experience.

PMID- 12183093
TI  - Assessment of patient-reported clinical outcome in pancreatic and other
      hepatobiliary cancers: the FACT Hepatobiliary Symptom Index.
AB  - This study's aim was to develop and validate a symptom index derived from the
      Functional Assessment of Cancer Therapy-Hepatobiliary, a questionnaire measuring
      general and hepatobiliary disease specific aspects of quality of life. The item
      pool was narrowed to 26 questions that assess symptoms and function. Each of 95
      hepatobiliary cancer experts narrowed the list to 5 of the most important to
      attend to when treating advanced hepatobiliary disease. Eight symptoms were
      endorsed by more than 20% of the experts (3 pain, 2 fatigue, nausea, weight loss,
      jaundice) and were named the FACT-Hepatobiliary Symptom Index-8 (FHSI-8). Among
      51 hepatobiliary cancer patients, the FHSI-8 showed good internal consistency
      (0.79), test-retest reliability (r = 0.86), strong association with mood (r = 
      0.56), and patient differentiation by ECOG Performance Status Rating ( P <
      0.0001) and treatment status ( P = 0.057). Symptom scaling in diseases such as
      hepatobiliary cancer is feasible and may provide an efficient, clinically
      relevant endpoint for following groups over time.

PMID- 12183094
TI  - Breakthrough cancer pain: prevalence and characteristics in patients in
      Catalonia, Spain.
AB  - Breakthrough pain (BTP), a transitory exacerbation of pain superimposed on a
      background of persistent, usually adequately controlled pain, has been reported
      to occur in 50% to 75% of cancer patients. However, a 23% prevalence of BTP was
      recently reported in a study of Spanish patients with advanced cancers, showing
      probably a low detection rate of this clinical problem. The purpose of the
      present study was to determine the prevalence of BTP among oncology patients
      managed by palliative care teams in Catalonia, Spain, and to characterize the
      frequency, intensity, and treatment of BTP episodes. Sixty-two teams studied 397
      patients on a predetermined index day. BTP was reported by 163 (41%) patients,
      with a total of 244 episodes (mean 1.5 episodes/patient/day). Mean (SD) intensity
      of BTP episodes was 7.3 (2.0), compared with 2.9 (2.7) for persistent pain (both
      0-10 scales). Morphine was used to treat 52% of BTP episodes, while 25% were
      untreated. These findings indicate that BTP remains underrecognized and
      undertreated in Spain.

PMID- 12183095
TI  - Family satisfaction with end-of-life care for cancer patients in a cluster
      randomized trial.
AB  - The main aim of this study was to examine similarities and differences in
      satisfaction with care between 112 family members who were close to patients who
      had participated in an intervention with a comprehensive palliative care program
      and the 68 family members in a conventional care program (controls). The FAMCARE
      Scale measured satisfaction with care at one month after the time of death. The
      majority of respondents reported high satisfaction with care. The respondents
      related to the patients in the intervention group reported significantly higher
      satisfaction with care than the respondents related to the patients in the
      control group. This difference remained unchanged after controlling for a range
      of other relevant factors: relationship to the deceased, sex and age of the
      respondent, sex and age of the patient, time since inclusion in the study, and
      place of death.

PMID- 12183096
TI  - Management of infections in palliative care patients with advanced cancer.
AB  - To characterize infections and their management in oncology patients at the end
      of life, we conducted a review of the literature. Eight studies assessing
      infection in 957 patients with various malignancies were identified. Forty-two
      percent of terminally ill patients developed infections in the final phase of
      care. The greatest frequency of treatment with antibiotics occurred in acute care
      hospitals. Enterobacteriaceae and S. aureus were the most frequently isolated
      bacteria, and urinary and respiratory tracts the most frequently involved sites
      of infection. A total of 19-39% of individuals with suspected infection and
      advanced cancer died. The decision whether to treat or not in the palliative care
      setting may be complex and requires an individualized approach. Further research
      in this area will help develop a consensus for management that will facilitate
      education of students and residents regarding complex decisions of care of
      infections at the end of life.

PMID- 12183097
TI  - Opioid antagonists: a review of their role in palliative care, focusing on use in
      opioid-related constipation.
AB  - Opioid antagonists have well-established indications in the reversal of life
      threatening opioid toxicity, but also hold considerable promise for other
      applications in palliative care practice, particularly management of opioid
      related constipation. We briefly review current understanding of opioid
      receptors, focusing on their complex role in gastrointestinal physiology. We
      summarize the pharmacology, conventional indications, and clinical usage of three
      major groups of opioid antagonists, including a promising new peripherally acting
      agent, methylnaltrexone, which is not commercially available. We suggest an
      approach to administering opioid antagonists for reduction of life-threatening
      opioid toxicity in patients with pain. The literature on opioid-induced
      constipation and its treatment with opioid-antagonists is reviewed in detail.
      Finally, other potential uses of opioid antagonists in palliative care are
      described, especially strategies for reducing such opioid side effects as nausea
      and pruritus and for improving analgesia or reducing tolerance by concomitantly
      administrating both an opioid agonist and low dosages of an antagonist.

PMID- 12183099
TI  - Ultrafine particles cause cytoskeletal dysfunctions in macrophages.
AB  - Essential cytoskeletal functions of macrophages are migration, phagocytosis of
      foreign materials, and intracellular transport and digestion The influence of
      fine and ultrafine test particles (UFP), such as TiO(2), elemental carbon,
      commercial carbon black, diesel exhaust particulate matter, and urban dust
      (UrbD), on cytoskeleton-related functions of macrophages, such as phagocytosis,
      phagosome transport mechanisms, and mechanical cytoskeletal integrity, were
      studied by flow cytometry and by cytomagnetometry. Additionally, necrosis and
      apoptosis caused by the test particles was detected. The diameter of the test
      particles ranged from 12 to 220 nm and the Brunauer-Emmet-Teller specific surface
      area ranged from 6 to 600 m(2)/g. Primary alveolar macrophages from beagle dogs
      (BD-AM), obtained by bronchoalveolar lavage, were used as well as macrophages
      originating from the cell line J774A.1. For cytomagnetometry studies, spherical
      1.8-microm ferromagnetic particles served as probes for cytoskeletal functions
      and were incubated together with the macrophages 24 h prior to UFP exposure.
      Macrophages were exposed in vitro with 10-320 microg UFP/ml/10(6) cells up to 24
      h. In all experiments, J774A.1 macrophages were more sensitive than BD-AM to UFP
      exposure. Cytoskeletal dysfunctions evaluated by cytomagnetometry were an
      impaired phagosome transport and an increased cytoskeletal stiffness and occurred
      at concentrations of 100 microg UFP/ml/10(6) cells and above, in both BD-AM and
      J774A.1. Only fine TiO(2) did not show any effect. Urban dust (standard reference
      material 1649a) and diesel exhaust particles (DEP, standard reference material
      1650) caused comparable cytoskeletal dysfunctions to elemental carbon with high
      specific surface area. Cytoskeletal dysfunctions induced by DEP or UrbD could be
      reduced after washing the particles by dichloromethane. UFP caused an impaired
      phagocytosis of 1-microm diameter fluorescent latex beads, inhibited cell
      proliferation, and decreased cell viability. All recorded cytotoxic parameters
      showed only weak correlations with the specific surface area or the total number
      of UFP, which can result from the different types of particles and different
      surface compositions. UFP cause cytoskeletal toxicity in vitro in macrophages,
      which can cause cellular dysfunctions, such as impaired proliferation, impaired
      phagocytic activity, and retarded intracellular transport processes as well as
      increased cell stiffness and can result in impaired defense ability in the lung.

PMID- 12183100
TI  - Mitochondria work as reactors in reducing arsenate to arsenite.
AB  - Arsenate (AsV) is a structural analogue of phosphate (P(i)), yet its toxic effect
      is likely due to its reduction to the more toxic arsenite (AsIII), the mechanism
      of which is still unclear. Since mitochondria take up AsV as they do P(i), they
      may reduce AsV to AsIII. To test this hypothesis isolated rat liver mitochondria
      were incubated with AsV, and the incubate was analyzed for AsV and AsIII by HPLC
      HG-AFS. Mitochondria rapidly reduced AsV to AsIII. Of the substrates supporting
      the citric acid cycle, glutamate enhanced the reduction most effectively. ADP
      increased, whereas AMP and ATP decreased, AsIII formation. These effects could be
      prevented by atractyloside. Electron transport inhibitors and uncouplers
      abolished AsIII formation, whereas ATP-synthase inhibitors almost completely
      inhibited it. Phosphate decreased AsIII formation in a concentration-dependent
      manner. Inhibitors of mitochondrial P(i)-moving transporters abolished AsIII
      formation. Sulfate, sulfite, or thiosulfate that are transported by the
      dicarboxylate carrier caused partial inhibition. AsIII was recovered completely
      from the supernatant of the mitochondrial incubate, suggesting that mitochondria
      exported the formed AsIII. Testing the effects on mitochondrial AsV reduction of
      chemicals that are inhibitors or substrates of thioredoxin reductase failed to
      support the role of this enzyme in reduction of AsV. Depletion of mitochondrial
      glutathione impaired mitochondrial AsV reducing activity but also diminished the
      respiratory control ratio. Upon solubilization of mitochondria, their AsV
      reducing activity was lost and was not recovered by addition of GSH and NADH or
      NADPH. Summarizing, mitochondria work as reactors: they take up AsV, rapidly
      reduce it, and export the formed AsIII. Disruption of functional or structural
      integrity of mitochondria severely impairs biotransformation of AsV into AsIII in
      this organelle.

PMID- 12183101
TI  - DNA damage induced by 4,4'-methylenedianiline in primary cultures of hepatocytes
      and thyreocytes from rats and humans.
AB  - 4,4'-Methylenedianiline (MDA), an aromatic amine used in various industrial
      processes and previously found to induce tumor development in liver and thyroid
      of mice and rats, was evaluated for its DNA-damaging activity in primary cultures
      of hepatocytes and thyreocytes from rat and human donors. After exposure for 4
      and 20 h to MDA concentrations ranging from 10 to 180 microM, a statistically
      significant increase in the frequency of DNA lesions was revealed by the Comet
      assay in primary hepatocytes and thyreocytes from donors of both species, the
      response being dose dependent up to 56-100 microM MDA. DNA fragmentation was more
      marked after 4 than after 20 h exposure in all four cell types. DNA was damaged
      to a lesser extent in human hepatocytes and thyreocytes than in corresponding rat
      cells and in both species in hepatocytes than in thyreocytes. In both rat and
      human hepatocytes a 20-h exposure to the same MDA concentrations elicited a
      modest amount of DNA repair synthesis, as evaluated by autoradiography. Evidence
      of a partial reduction of DNA damage, and therefore of only partial DNA repair,
      was observed in rat hepatocytes and in rat and human thyreocytes incubated for 16
      h in MDA-free medium after a 4-h MDA treatment. A 4-h exposure to 56, 100, and
      180 microM MDA did not induce DNA lesions in primary cultures of cells from three
      rat organs, kidney, urinary bladder mucosa, and brain, which are resistant to MDA
      carcinogenic activity. Under the same experimental conditions any evidence of DNA
      damage was absent in primary kidney and urinary bladder cells from human donors.
      Taken as a whole the results of this work indicate that MDA is specifically
      activated to DNA-damaging reactive species by hepatocytes and thyreocytes in both
      rats and humans and thus suggest that liver and thyroid might be the targets of
      the carcinogenic activity of MDA also in humans.

PMID- 12183102
TI  - Elucidating changes in surface marker expression of dendritic cells following
      chemical allergen treatment.
AB  - Dendritic cells (DC) are highly specialized antigen-presenting cells (APC)
      located in lymphoid and many nonlymphoid tissues, and Langerhans cells (LC), a
      specialized form of DC, are found in the skin. LC play a critical role in the
      induction of contact dermatitis and therefore have become a focal point for the
      development of in vitro cell-based methods for contact sensitization testing.
      Because of the low abundance of skin-derived LC, methods to culture DC from
      peripheral blood are being used by investigators to generate LC surrogates to
      examine the effects of sensitizing chemicals on APC. It has been reported
      recently that chemical allergens can induce changes in the expression of various
      DC surface markers and it has been suggested that the measure of these changes in
      surface marker expression following allergen treatment could provide the basis
      for an in vitro test method to predict the contact sensitization potential of a
      chemical. For the work presented here, DC were differentiated from human
      peripheral blood mononuclear cells (PBMC-DC) in culture medium containing GM-CSF
      and interleukin (IL)-4 to ensure an immature phenotype or were derived from the
      KG-1 cell line (KG-1 DC) using a defined cytokine cocktail consisting of GM-CSF,
      IL-4, Flt-3/Flk-2-ligand, thrombopoietin, stem cell factor, and tumor necrosis
      factor-alpha (TNFalpha). Surface marker expression (HLA-DR, CD54, CD80, and CD86)
      on these DC was measured by flow cytometry after 48 h treatment with the known
      chemical allergens dinitrofluorobenzene (DNFB) and
      methylchloroisothiazolinone/methylisothiazolinone (MCI/MI), the irritant sodium
      dodecyl sulfate, lipopolysaccharide (LPS), and TNFalpha. Treatment of PBMC-DC
      with either MCI/MI or DNFB induced a slight upregulation of class II major
      histocompatibility (MHC) expression (HLA-DR), whereas LPS and TNFalpha
      significantly upregulated CD54 and slightly upregulated CD80 and HLA-DR
      expression. For KG-1 DC, only MCI/MI upregulated CD86 expression, whereas
      TNFalpha upregulated CD54 and slightly upregulated CD80 and CD86 expression. SDS
      had no effect on surface marker expression in either PBMC-DC or KG-1 DC. Changes
      in surface marker expression in PBMC-DC treated with chemical allergens were
      detected in two of five donors, suggesting a limited sensitivity of PBMC-DC under
      these defined isolation and culture conditions. Furthermore, we found that the
      presence of GM-CSF and IL-4 during chemical allergen treatment masked the ability
      to detect changes in surface marker expression. Our data suggest that, under
      these culture and treatment conditions, measurement of surface marker changes in
      vitro using PBMC-DC or KG-1 DC does not provide a sensitive in vitro method with
      sufficient dynamic range for assessing the contact sensitization potential of a
      chemical.

PMID- 12183103
TI  - Renal organic anion transport system: a mechanism for the basolateral uptake of
      mercury-thiol conjugates along the pars recta of the proximal tubule.
AB  - The basolateral handling of 20 microM inorganic mercury (Hg(2+)), in the form of
      mercuric conjugates of cysteine (Cys), N-acetylcysteine (NAC), or glutathione
      (GSH), was studied in isolated perfused S2 segments of the rabbit proximal
      tubule. One of the primary aims of the present study was to determine in a direct
      manner whether basolateral uptake of Hg(++) occurs in the pars recta of the
      proximal tubule and, more importantly, whether the p-aminohippurate-sensitive
      (PAH) organic anion transport system is involved in this process. Basolateral
      uptake and accumulation of Hg(++) occurred when the basolateral membrane of the
      tubular segments was exposed to mercuric conjugates of Cys, NAC, or GSH. Net
      basolateral uptake of Hg(++) was more than twice as great in the tubules exposed
      to mercuric conjugates of Cys or NAC than in the tubules exposed to mercuric
      conjugates of GSH, indicating that mercuric conjugates of Cys or NAC are
      transported more efficiently than mercuric conjugates of GSH. When PAH (1 mM) was
      added to the basolateral compartment (bath) surrounding a perfused S2 segment,
      the net uptake of Hg(++) (in the form of the mercuric conjugates) was reduced by
      60-70%. In addition, when glutarate (4 mM), a transportable substrate for both
      the sodium-dependent dicarboxylate transporter and the dicarboxylate/organic
      anion exchanger (OAT1), was added to the basolateral compartment, there was a
      significant reduction in the uptake and accumulation of Hg(++) in the form of
      mercuric conjugates of Cys. Overall, these data indicate that Hg(++), in the form
      of biologically relevant mercuric conjugates of Cys, NAC, or GSH, is taken up
      significantly at the basolateral membrane of pars recta segments of the proximal
      tubule, and this uptake is mediated mainly by the actions of the PAH-sensitive
      organic anion transport system.

PMID- 12183104
TI  - Metabolism and toxicity of trichloroethylene in epididymis and testis.
AB  - The widespread occupational exposure to trichloroethylene (TCE) led us to test
      the hypothesis that TCE causes toxicity in the male reproductive system. We also
      investigated mechanisms mediating the potential cytotoxic response. Mice were
      exposed to TCE (1000 ppm) by inhalation for 6 h/day for 5 days/week for a total
      of 19 days. Exposure after the first week was interspersed by a "weekend." To
      estimate internal exposure, we measured the TCE metabolites, trichloroacetic acid
      (TCA) and trichloroethanol (TCOH), in urine at Days 4, 9, 14, and 19. Urinary
      excretion of TCOH was significantly higher than TCA; levels of TCOH and TCA
      significantly increased by the second and third week, respectively. Cytochrome
      P450 2E1 (CYP2E1), an enzyme involved in TCE metabolism, was localized in the
      epididymal epithelium and testicular Leydig cells, and was found at higher levels
      in the former than the latter. Immunoblotting confirmed that CYP2E1 protein was
      present in greater amounts in epididymis than in testis. p-Nitrophenol
      hydroxylation, a CYP2E1 catalytic activity, was also higher in the epididymis
      than in the testis. Chloral, a major TCE metabolite, was generated in microsomal
      incubations at significantly higher levels in epididymis than in testis. Antibody
      inhibition of CYP2E1 reduced chloral formation, which was more pronounced in
      epididymis than in testis. After 4 weeks of TCE exposure, damage to the
      epididymis was manifested as sloughing of epithelial cells. These results
      indicated that TCE is metabolized in the male reproductive tract, leading to
      adverse effects that are more severe in the epididymis than in the testis.

PMID- 12183105
TI  - Cadherins and NCAM as potential targets in metal toxicity.
AB  - Cell adhesion molecules are cell surface proteins that play critical roles in
      cell recognition and cell adhesion. These adhesion molecules, which include the
      cadherins, integrins, occludins, and a variety of immunoglobulin-like molecules,
      are essential for a wide variety of physiologic processes such as epithelial
      barrier function, tissue development, learning and memory, and immune responses.
      In light of the evidence that toxic metals can affect many of these processes,
      investigators have begun to examine the possibility that cell adhesion molecules
      may be targets for metal toxicity. This review summarizes the results of recent
      studies showing that certain cell adhesion molecules, particularly the cadherins
      family of Ca(2+)-dependent cell adhesion molecules and the immunoglobulin family
      of Ca(2+)-independent cell adhesion molecules, may be important early targets on
      which toxic metals such as a Cd, Hg, and Pb act to produce their toxic effects.
      These metals, and in some cases their organic compounds, can target cell adhesion
      molecules at multiple levels, including protein-protein interactions, post
      translational modification, and transcriptional regulation. Moreover, by
      interfering with the normal function of the cadherin family of cell adhesion
      molecules, some of these metals may activate the beta-catenin nuclear signaling
      pathway. These studies have provided important new insights into the molecular
      mechanisms of metal toxicity and have opened several exciting avenues of
      research.

PMID- 12183106
TI  - Positron emission tomography.

PMID- 12183107
TI  - Positron emission tomography: the conceptual idea using a multidisciplinary
      approach.
AB  - Positron emission tomography (PET) is a method for quantitatively measuring
      biochemical and physiological processes in vivo by using radiopharmaceuticals
      labeled with positron-emitting radionuclides such as 11C, 13N, 15O, and 18F and
      by measuring the annihilation radiation using a coincidence technique. This
      technique is also used for measurement of the pharmacokinetics of labeled drugs
      and measurement of the effects of drugs on metabolism. Deviations from normal
      metabolism can be measured and insight into biological processes responsible for
      diseases can be obtained.

PMID- 12183108
TI  - Radiopharmaceutical chemistry for positron emission tomography.
AB  - Radiopharmaceutical chemistry includes the selection, preparation, and
      preclinical evaluation of radiolabeled compounds. This paper describes selection
      criteria for candidates for positron emission tomography (PET) investigations.
      Practical aspects of nucleophilic and electrophilic (18)F-fluorinations and (11)C
      methylations are described. These aspects include production of fluorine-18 and
      carbon-11, workup of fluorine-18, (18)F radiochemistry, production of
      [(11)C]methyl iodide and triflate, and (11)C-methylation radiochemistry.

PMID- 12183109
TI  - Measurement of glucose consumption using [(18)F]fluorodeoxyglucose.
AB  - The [(18)F]fluorodeoxyglucose (FDG) method to measure glucose metabolism
      quantitatively in humans is reviewed. The assumptions and the mathematical
      formulation of the underlying autoradiographic Sokoloff model and its adaptation
      to positron emission tomography (PET) are described. Various implementations to
      estimate glucose consumption from measured tissue activity with PET are
      presented. The dependence on the "lumped constant" and on the accuracy of the
      input function is discussed. Recommendations for the practical application of
      different procedures for performing FDG studies are given.

PMID- 12183110
TI  - Positron emission tomography: measurement of myocardial perfusion using (13)N
      labeled ammonia and (15)O-labeled water.

PMID- 12183111
TI  - Dynamics of multidrug resistance: P-glycoprotein analyses with positron emission
      tomography.
AB  - Multidrug resistance (MDR) is characterized by the occurrence of cross-resistance
      to a broad range of structurally and functionally unrelated drugs. Several
      mechanisms are involved in MDR. One of the most well-known mechanisms is the
      overexpression of P-glycoprotein (P-gp), encoded by the MDR1 gene in humans and
      by the mdr1a and mdr1b genes in rodents. P-gp is extensively expressed in the
      human body, e.g., in the blood-brain barrier and also in solid tumor tissue.
      Overexpression of P-gp on tumor membranes might result in MDR of human tumors. To
      circumvent this resistant phenotype, several P-gp modulators such as cyclosporin
      A (CsA) are available. Competition between P-gp drugs and modulators results in
      decreased transport of the drug out of tumor tissue and an increased cellular
      level of these drugs. For effective clinical treatment it is important to have
      knowledge about P-gp functionality in tumors. Therefore, we have developed a
      method to measure the P-gp functionality in vivo with PET and [(11)C]verapamil as
      a positron-emitting P-gp substrate. The results obtained in rodents and in cancer
      patients are described in this article.

PMID- 12183112
TI  - Positron emission tomography: measurement of transgene expression.
AB  - Noninvasive and repetitive imaging of transgene expression can play a pivotal
      role in the development of gene therapy strategies, as it offers investigators a
      means to determine the effectiveness of their gene transfection protocols. In the
      last decade, imaging of transgene expression using positron emission tomography
      (PET) or single-photon emission computed tomography (SPECT) has received
      considerable attention and as a result several imaging methods have now been
      evaluated in animals. As a typical example of noninvasive imaging of transgene
      expression, this article describes the principles of monitoring the expression of
      the herpes simplex virus type 1 thymidine kinase gene with PET, using the
      ganciclovir analog 9-(3-[18F]fluoro-1-hydroxy-2-propoxy)methylguanine as the
      tracer. In addition to a description of the execution of the PET scan and data
      analysis, the types of transgene animal models that are applied and the principal
      limitations of the imaging technique are summarized. Finally, several indirect
      approaches to image transgenes via a linked reporter gene are discussed.

PMID- 12183113
TI  - Positron emission tomography: quantitative measurement of brain
      acetylcholinesterase activity using radiolabeled substrates.
AB  - A new method for quantitative measurement of brain acetylcholinesterase (AChE)
      activity in living human brain using positron emission tomography (PET) is
      described. We tested several radiolabeled lipophilic acetylcholine analogs, e.g.,
      N-methylpiperidyl esters, which readily entered the brain via the blood-brain
      barrier, were hydrolyzed selectively by AChE, and were then trapped in the brain.
      Among them, and tested and N-[11C]methylpiperidin-4-yl acetate ([11C]MP4A) was
      chosen as the tracer for PET. Quantitative measurement of cortical AChE was
      accomplished by fitting the time course of cerebral radioactivity concentration
      measured by PET and the metabolite-corrected arterial plasma input function using
      a nonlinear least-squares fitting method. Normal control studies of subjects with
      a wide range in age (24-89 years) showed no decrease in AChE activity in the
      cerebral cortex with age. Studies on patients with Alzheimer's disease
      demonstrated a widespread reduction of AChE activity in the cerebral cortex (more
      profound in early-onset than in late-onset Alzheimer's disease). Parkinson's
      disease and progressive supranuclear palsy, clinically similar disorders, could
      be differentiated with [11C]MP4A/PET studies. Simple methods without using an
      arterial input function are also proposed. The method provides a quantitative
      measure of the cholinergic aspect of brain function and proved to be useful in
      diagnosis of neurodegenerative disorders including Alzheimer's disease.

PMID- 12183114
TI  - Positron emission tomography: measurement of the activity of second messenger
      systems.
AB  - Phosphoinositide turnover is closely connected to modulation of synaptic function
      and is part of an important second messenger-producing system. New radioligands
      for imaging second messenger systems by positron emission tomography have been
      developed: carbon-11-labeled 1,2-diacylglycerols. The theoretical background of
      second messenger imaging is described in detail and the relation between the
      biologically active compounds and potential tracers for imaging second messenger
      systems is discussed. We report informative findings on postsynaptic biological
      responses in the living human brain of healthy normal subjects and with various
      diseases.

PMID- 12183115
TI  - Monoamine oxidase: radiotracer development and human studies.
AB  - Monoamine oxidase (MAO) is an integral protein of outer mitochondrial membranes
      and occurs in neuronal and nonneuronal cells in the brain and in peripheral
      organs. It oxidizes amines from both endogenous and exogenous sources, thereby
      influencing the concentration of neurotransmitter amines as well as many
      xenobiotics. It occurs in two subtypes, MAO A and MAO B, which are different gene
      products and have different substrate and inhibitor specificities. Both MAO A and
      B can be imaged and quantified in the living human brain using positron emission
      tomography (PET) and radiotracers labeled with carbon-11. PET studies have been
      carried out to measure the effects of age, MAO inhibitor drugs, tobacco smoke
      exposure, and other factors on MAO activity in the human brain.

PMID- 12183116
TI  - Measuring drug-related receptor occupancy with positron emission tomography.
AB  - Several techniques can be used to measure indirectly the effect of drugs (e.g.,
      EEG, fMRI) in healthy volunteers and in patients. Although each technique has its
      merits, a direct link between drug efficacy and site of action in vivo usually
      cannot be established. In addition, when the specific mode of action of a drug
      has been determined from preclinical studies, it is often not known whether the
      administered dose is optimal for humans. Both industry and academia are becoming
      more and more interested in determining the dose-related occupancy of specific
      targets caused by administration of drugs under test. Positron emission
      tomography (PET) and single-photon emission computed tomography (SPECT) are
      noninvasive imaging techniques that can give insight into the relationship
      between target occupancy and drug efficacy, provided a suitable radioligand is
      available. Although SPECT has certain advantages (e.g., a long half-life of the
      radionuclides), the spatial and temporal resolution as well as the labeling
      possibilities of this technique are limited. This review focuses on PET
      methodology for conducting drug occupancy studies in humans.

PMID- 12183117
TI  - Positron emission tomography: imaging and quantification of neurotransporter
      availability.
AB  - Over the last decade, a large number of radiotracers have been developed to image
      and quantify transporter availability with positron emission tomography (PET) or
      single-photon emission computed tomography (SPECT). Radiotracers suitable to
      image dopamine transporters (DATs) and serotonin transporters (SERTs) have been
      the object of most efforts. Following a brief overview of DAT and SERT
      radiotracers that have been demonstrated to be suitable for quantitative analysis
      in vivo, this article describes the principal methods that have been used for the
      analysis of these data. Kinetic modeling is the most direct implementation of the
      compartment models, but with some tracers accurate input function measurement and
      good compartment configuration identification can be difficult to obtain. Other
      methods were designed to overcome some particular vulnerability to error of
      classic kinetic modeling, but introduced new vulnerabilities in the process.
      Reference region methods obviate the need for arterial plasma measurement, but
      are not as robust to violations of the underlying modeling assumptions as methods
      using the arterial input function. Graphical methods give estimates of
      distribution volumes without the requirement of compartment model specification,
      but provide a biased estimator in the presence of statistical noise. True
      equilibrium methods are quite robust, but their use is limited to experiments
      with tracers that are suitable for constant infusion. In conclusion, no
      universally "best" method is applicable to all neurotransporter imaging studies,
      and careful evaluation of model-based methods is required for each radiotracer.

PMID- 12183118
TI  - Functional continuum of regulatory peptides (RPs): vector model of RP-effects
      representation.
AB  - During the past decades, bioactive (regulatory) peptides have been identified as
      the major players in the regulation of many important biological processes.
      Dozens of peptides have found their application as pharmaceutical agents, which
      further stimulated research in this field making it one of the most rapidly
      developing areas on the edge of biological science and medicine. However, the
      fast accumulation of enormous amounts of experimental data has revealed a great
      difficulty in their analysis and demanded the development of a systematic
      approach for generalization of the obtained information. We propose a new
      computer-based algorithm for studying biological activities of regulatory
      peptides and their groups based on their representation as vectors in n 
      dimensional functional space. Our method allows the rapid analysis of databases
      containing thousands of polyfunctional regulatory peptides with overlapping
      spectra of physiological activity. The described method permits to perform
      several types of correlations which, when applied to the large databases, could
      reveal new important information about the system of regulatory peptides. It can
      select the groups of peptides with similar physiological role (peptide
      constellations) and search for the optimal peptide combinations with
      predetermined spectrum of effects and minimal side effects for their further
      pharmacological application. It can also reveal the role of regulatory peptides
      in induction of chain physiological reactions.

PMID- 12183119
TI  - A mathematical model for the germinal center morphology and affinity maturation.
AB  - During germinal center reactions, the appearance of two specific zones are
      observed: the dark and the light zone. Up to now, the origin and function of
      these zones are poorly understood. In the framework of a stochastic and discrete
      model, several possible pathways of zone development during germinal center
      reactions are investigated. The importance of the zones in the germinal center
      for affinity maturation, i.e. the process of antibody optimization is discussed.

PMID- 12183121
TI  - Test of a statistical model for molecular recognition in biological repertoires.
AB  - A chance encounter between members of a random repertoire and a molecular target
      is characteristic of different biological systems, including the immune and
      olfactory pathways as well as combinatorial libraries. In such systems, the
      affinity between the target and members of the repertoire is distributed with a
      probability function describing the propensity of obtaining a particular affinity
      value. We have previously proposed a phenomenological receptor affinity
      distribution (RAD) formalism, which describes this probability function based on
      simple statistical considerations. In the present analysis, we use published data
      from diverse experimental systems, including phage display libraries,
      immunoglobulins and enzymes, to test the RAD model and to compare it to other
      affinity distribution formalisms. The RAD model is found to provide the best
      description for binding data for over eight orders of magnitude on the affinity
      scale, and to account for a relationship between repertoire size and the maximal
      obtainable affinity within different repertoires. This approach points to a
      potential universality of the rules that govern affinity distributions in
      biology.

PMID- 12183120
TI  - Exploring the formation of Alzheimer's disease senile plaques in silico.
AB  - An experimental simulation environment suitable for exploring the
      neuroinflammatory hypothesis of Alzheimer's disease (AD) has been developed.
      Using scientific literature, we have calculated parameters and rates and
      constructed an interactive model system. The simulation can be manipulated to
      explore competing hypotheses about AD pathology, i.e. can be used as an
      experimental "in silico" system. In this paper, we outline the assumptions and
      aspects of the model, and illustrate qualitative and quantitative findings. The
      interactions of amyloid beta deposits, glial cell dynamics, inflammation and
      secreted cytokines, and the stress, recovery, and death of neuronal tissue are
      investigated. The model leads to qualitative insights about relative roles of the
      cells and chemicals in the disease pathology.

PMID- 12183122
TI  - Modeling the process of rate selection in neuronal activity.
AB  - We present the elements of a mathematical computational model that reflects the
      experimental finding that the time-scale of a neuron is not fixed; but rather
      varies with the history of its stimulus. Unlike most physiological models, there
      are no pre-determined rates associated with transitions between states of the
      system nor are there pre-determined constants associated with adaptation rates;
      instead, the model is a kind of "modulating automata" where the rates emerge from
      the history of the system itself. We focus in this paper on the temporal dynamics
      of a neuron and show how a simple internal structure will give rise to complex
      temporal behavior. The internal structure modeled here is an abstraction of a
      reasonably well-understood physiological structure. We also suggest that this
      behavior can be used to transform a "rate" code into a "temporal one".

PMID- 12183123
TI  - Are diabetic neuropathy, retinopathy and nephropathy caused by hyperglycemic
      exclusion of dehydroascorbate uptake by glucose transporters?
AB  - Vitamin C exists in two major forms. The charged form, ascorbic acid (AA), is
      taken up into cells via sodium-dependent facilitated transport. The uncharged
      form, dehydroascorbate (DHA), enters cells via glucose transporters (GLUT) and is
      then converted back to AA within these cells. Cell types such as certain
      endothelial and epithelial cells as well as neurons that are particularly prone
      to damage during diabetes tend to be those that appear to be dependent on GLUT
      transport of DHA rather than sodium-dependent AA uptake. We hypothesize that
      diabetic neuropathies, nephropathies and retinopathies develop in part by
      exclusion of DHA uptake by GLUT transporters when blood glucose levels rise above
      normal. AA plays a central role in the antioxidant defense system. Exclusion of
      DHA from cells by hyperglycemia would deprive the cells of the central
      antioxidant, worsening the hyperglycemia-induced oxidative stress level.
      Moreover, AA participates in many cellular oxidation-reduction reactions
      including hydroxylation of polypeptide lysine and proline residues and dopamine
      that are required for collagen production and metabolism and storage of
      catecholamines in neurons. Increase in the oxidative stress level and metabolic
      perturbations can be expected in any tissue or cell type that relies exclusively
      or mainly on GLUT for co-transport of glucose and DHA including neurons,
      epithelial cells, and vascular tissues. On the other hand, since DHA represents a
      significant proportion of total serum ascorbate, by increasing total plasma
      ascorbate concentrations during hyperglycemia, it should be possible to correct
      the increase in the oxidative stress level and metabolic perturbations, thereby
      sparing diabetic patients many of their complications.

PMID- 12183124
TI  - Amino acid encoding schemes from protein structure alignments: multi-dimensional
      vectors to describe residue types.
AB  - Bioinformatic software has used various numerical encoding schemes to describe
      amino acid sequences. Orthogonal encoding, employing 20 numbers to describe the
      amino acid type of one protein residue, is often used with artificial neural
      network (ANN) models. However, this can increase the model complexity, thus
      leading to difficulty in implementation and poor performance. Here, we use ANNs
      to derive encoding schemes for the amino acid types from protein three
      dimensional structure alignments. Each of the 20 amino acid types is
      characterized with a few real numbers. Our schemes are tested on the simulation
      of amino acid substitution matrices. These simplified schemes outperform the
      orthogonal encoding on small data sets. Using one of these encoding schemes, we
      generate a colouring scheme for the amino acids in which comparable amino acids
      are in similar colours. We expect it to be useful for visual inspection and
      manual editing of protein multiple sequence alignments.

PMID- 12183125
TI  - A method for the calculation of odor character from molecular structure.
AB  - The relationship between molecular structure and odor character is one of the
      most complex structure-activity problems in biology. Despite over a century of
      effort, it remains unsolved, and synthesis of new odorants still proceeds largely
      by trial and error. In previous work, I have argued that the reason for this
      failure lies in a mistaken assumption, namely that molecular shape determines
      odor character. Instead, I have taken up and extended an old idea (Dyson, 1938)
      according to which vertebrate olfactory receptors detect odorants by their
      molecular vibrations. I propose that the detection mechanism is inelastic
      electron tunnelling. If this is correct, there should be a correlation between
      the tunnelling vibrational spectra of odorants and their odor character. Here,
      using semi-empirical quantum chemistry methods and a simple calculation method
      for tunnelling mode intensities, I calculate the spectra of structurally diverse
      odorants belonging to various odor categories. With few exceptions, the
      calculated spectra of bitter almonds, musks, ambers, woods, sandalwoods and
      violets strongly correlate with odor character.

PMID- 12183126
TI  - Kinetic analysis of multisite phosphorylation using analytic solutions to
      Michaelis-Menten equations.
AB  - Phosphorylation-induced expression or modulation of a functional protein is a
      common signal in living cells. Many functional proteins are phosphorylated at
      multiple sites and it is frequently observed that phosphorylation at one site
      enhances or suppresses phosphorylation at another site. Therefore, characterizing
      such cooperative phosphorylation is important. In this study, we determine a
      temporal progress curve of multisite phosphorylation by analytically integrating
      the Michaelis-Menten equations in time. Using this theoretical progress curve, we
      derive the useful criterion that an intersection of two progress curves implies
      the presence of cooperativity. Experiments generally yield noisy progress curves.
      We fit the theoretical progress curves to noisy progress curves containing 4%
      Gaussian noise in order to determine the kinetics of the phosphorylation. This
      fitting correctly identifies the sites involved in cooperative phosphorylation.

PMID- 12183127
TI  - Evolutionarily stable leaf area production in plant populations.
AB  - Using an analytical model, it was shown that for a given amount of nitrogen in
      the canopy of a stand (N(T)), there exists an evolutionarily stable leaf area
      index (ES-LAI), and therefore an evolutionarily stable average leaf nitrogen
      content (n(ES)(av);n(ES)(av) =N(T)/ES-LAI), at which no individual plant in the
      stand can increase its photosynthesis by changing its leaf area. It was also
      shown that this ES-LAI is always greater than the optimal LAI that maximizes
      photosynthesis per unit N(T) of the stand. This illustrates that the canopy
      structure that maximizes photosynthesis of a population is not the same as the
      canopy structure that maximizes photosynthesis of individuals within a
      population. It was further derived that the ES-LAI at given N(T) increases with
      the ratio between the light-saturated photosynthesis and the N content per unit
      leaf area (leaf-PPNUE) and that it decreases with the canopy extinction
      coefficient for light (K(L)), the light availability and the apparent quantum
      yield (phi). These hypotheses were tested by comparing calculated ES-LAI and
      n(ES)(av) values to actual LAIs and leaf N contents measured for stands of a
      large variety of herbaceous plants. There was a close correspondence between the
      calculated and measured values. As predicted by the model, plants with high leaf
      PPNUEs produced more leaf area per unit nitrogen than those with low leaf-PPNUEs
      while plants with horizontal leaves, forming stands with higher K(L) values,
      produced less leaf area than those with more vertically inclined leaves. These
      results suggest that maximization of individual plant photosynthesis per unit of
      nitrogen plays an important role in determining leaf area production of plants
      and the resulting canopy structure of stands of vegetation. They further suggest
      this optimization to be a mechanism by which leaf traits such as leaf-PPNUE and
      leaf inclination angle are causally related to structural characteristics of the
      population, i.e. the leaf area index of the stand.

PMID- 12183128
TI  - Kinetic properties of the enzyme-substrate system: a basis for immediate
      temperature compensation.
AB  - One-minimum U-shaped temperature profiles of the dissociation constant (K(m))
      have been observed experimentally with a variety of enzyme-substrate (E-S)
      systems. The increase of E-S affinity with falling temperature ("positive thermal
      modulation of affinity"), which opposes the cold-induced reduction in catalytic
      velocity, has been often interpreted as significant for both immediate and
      evolutionary temperature compensations and of major importance in setting thermal
      limits in ectothermic organisms. This role was denied to enzymes from endotherms,
      on the ground that their minimal K(m) values were situated well below their
      normal body temperature. Evidence is presented in this report that affinity
      changes described by U-shaped profiles can simply be the consequence of intrinsic
      kinetic properties of the E-S system. Theoretical modeling is achieved by
      combining the classical expression for the Michaelis constant with Transition
      State Theory expressions for the three rate constants involved. It provides for
      the U-shape of the K(m) vs. T profile and allows for the derivation of an
      equation for identifying its inversion point. Modeling of V(max) and V(min)
      (reaction velocity under conditions of substrate saturation and of dilution,
      K(m)>>[S], respectively) is also included. An expression was formulated for
      predicting the "critical temperature," T(C), corresponding to the low-temperature
      break in Arrhenius lines. Using existing K(m) data from literature, concerning a
      variety of E-S systems, our modeling proved to be highly satisfactory. Our own
      experiments show that glucose uptake by rat brain synaptosomes can be regarded as
      a special case of basically the same kinetic scheme, and that the U-shaped
      temperature modulation of apparent K(m) for glucose conversion is also in full
      agreement with our kinetic modeling. These experiments indicate that positive
      thermal modulation, although based on intrinsic kinetic properties of the
      underlying E-S system, may have an adaptive role in endotherms as well, linked,
      however, to their tolerance to hypothermia.

PMID- 12183129
TI  - On the allometry of biomass partitioning and light harvesting for plants with
      leafless stems.
AB  - Prior explicit allometric models are extended to predict the scaling relationship
      between the ability of plants with leafless stems to harvest sunlight H and total
      standing plant biomass M(T) (which equals the sum of standing stem and root
      biomass, M(S) and M(R)). Provided that H scales in a directly proportional manner
      (isometrically) with respect to either stem surface area (i.e.H proportional,
      variant SA(S) ) or total stem biomass (i.e. H proportional, variant M(S)), the
      allometric model presented here predicts that SA(S) proportional, variant
      M(T)(3/4) or M(S) proportional, variant M(T)(3/4), respectively. These
      alternative predictions are tested empirically using data for standing stem and
      root biomass gathered for the large columnar cactus species Pachycereus pringlei.
      Statistical comparisons between observed and predicted scaling relationships
      indicate that SA(S) proportional, variant M(T)(3/4), whereas M(S) proportional,
      variant M(T)(3/4) is mathematically inconsistent with the observation that stem
      biomass scales nearly isometrically with respect to root biomass. The contention
      that the H of leafless stems scales isometrically with respect to stem surface
      area is thus reasonable both theoretically and empirically.

PMID- 12183130
TI  - The consequence of maximum thermodynamic efficiency in Daisyworld.
AB  - The imaginary planet of Daisyworld is the simplest model used to illustrate the
      implications of the Gaia hypothesis. The dynamics of daisies and their radiative
      interaction with the environment are described by fundamental equations of
      population ecology theory and physics. The parameterization of the turbulent
      energy flux between areas of different biological cover is similar to the
      diffusive-type approximation used in simple climate models. Here I show that the
      small variation of the planetary diffusivity adopted in the classical version of
      Daisyworld limits the range of values for the solar insolation for which biota
      may grow in the planet. Recent studies suggest that heat transport in a turbulent
      medium is constrained to maximize its efficiency. This condition is almost
      equivalent to maximizing the rate of entropy production due to non-radiative
      sources. Here, I apply the maximum entropy principle (MEP) to Daisyworld. I
      conclude that the MEP sets the maximum range of values for the solar insolation
      with a non-zero amount of daisies. Outside this range, daisies cannot grow in the
      planet for any physically realistic climate distribution. Inside this range, I
      assume a distribution of daisies in agreement with the MEP. The results
      substantially enlarge the range of climate stability, due to the biota, in
      comparison to the classical version of Daisyworld. A very stable temperature is
      found when two different species grow in the planet.

PMID- 12183131
TI  - Estimation of the highest chromosome number of eukaryotes based on the minimum
      interaction theory.
AB  - According to the minimum interaction theory, the chromosome evolution of
      eukaryotes proceeds as a whole toward increasing the chromosome number. This
      raises the following two questions: what was the starting chromosome number of
      eukaryotes and does the chromosome number increase infinitely? We attempted to
      provide a theoretical framework to resolve these questions. We propose that the
      species with n=2 observed in Protozoa, Platyhelminthes, Annelid, Algae, Fungi and
      higher plants would be chromosomal relicts conserving the karyotypes of ancestral
      eukaryotes. We also propose that the ideal highest number of eukaryotes (n(max))
      can be given by an inverse of the minimum terminal interference distance
      (It(min)) in crossing-over (n(max)=100/It(min)). AsIt(min) =0.6 in mammals,
      n(max) approximately 166. On the other hand, the value estimated by computer
      simulations is somewhat lower with n(max)=133-138. Our arguments can be applied
      to other eukaryotes, if they have a localized centromere and the ratio of total
      synaptonemal complex/nuclear volume is comparable to that of mammals. We revealed
      that the index of gene shuffling per karyotypes (G) by means of the total number
      of gamete types with different gene combinations can be formulated asG =2(n+Fxi),
      where Fxi means interstitial chiasma frequency per cell corresponding to crossing
      over mediated by the recombination nodule. The Fxi value increases in proportion
      to the n value in areas where n<40, but decreases gradually when n>40 and becomes
      zero when n>83. Therefore, in the ultimate karyotype with n(max)=166, FXi=0 andG
      =2(n)=2(166), where gene shuffling is guaranteed by the random orientation of
      chromosomes at the equatorial plate of meiotic metaphase I.

PMID- 12183132
TI  - A first formal link between the price equation and an optimization program.
AB  - The Darwin unification project is pursued. A meta-model encompassing an important
      class of population genetic models is formed by adding an abstract model of the
      number of successful gametes to the Price equation under uncertainty. A class of
      optimization programs are defined to represent the "individual-as-maximizing
      agent analogy" in a general way. It is then shown that for each population
      genetic model there is a corresponding optimization program with which formal
      links can be established. These links provide a secure logical foundation for the
      commonplace biological principle that natural selection leads organisms to act as
      if maximizing their "fitness", provides a definition of "fitness", and clarifies
      the limitations of that principle. The situations covered do not include
      frequency dependence or social behaviour, but the approach is capable of
      extension.

PMID- 12183133
TI  - 2nd to 4th digit ratio and offspring sex ratio.
AB  - There is evidence that the ratio of the length of the 2nd and 4th digit (2D:4D)
      is negatively related to prenatal and adult concentrations of testosterone. It
      has also been reported that high levels of testosterone at conception in both
      fathers and mothers are associated with an increased sex ratio (proportion of
      males at birth). It follows from these observations that low values of 2D:4D may
      be related to high sex ratio. We present evidence from three populations
      (English, Spanish and Jamaican) that 2D:4D is negatively related to sex ratio,
      independent of the sex and ethnicity of the parents.

PMID- 12183134
TI  - Labyrinthine Turing pattern formation in the cerebral cortex.
AB  - I propose that the labyrinthine patterns of the cortices of mammalian brains may
      be formed by a Turing instability of interacting axonal guidance species acting
      together with the mechanical strain imposed by the interconnecting axons.

PMID- 12183135
TI  - Modeling extracellular matrix degradation balance with
      proteinase/transglutaminase cycle.
AB  - Extracellular matrix mass balance is implied in many physiological and
      pathological events, such as metastasis dissemination. Widely studied, its
      destructive part is mainly catalysed by extracellular proteinases. Conversely,
      the properties of the constructive part are less obvious, cellular neo-synthesis
      being usually considered as its only element. In this paper, we introduce the
      action of transglutaminase in a mathematical model for extracellular matrix
      remodeling. This extracellular enzyme, catalysing intermolecular protein cross
      linking, is considered here as a reverse proteinase as far as the extracellular
      matrix physical state is concerned. The model is based on a
      proteinase/transglutaminase cycle interconverting insoluble matrix and soluble
      proteolysis fragments, with regulation of cellular proteinase expression by the
      fragments. Under "closed" (batch) conditions, i.e. neglecting matrix influx and
      fragment efflux from the system, the model is bistable, with reversible
      hysteresis. Extracellular matrix proteins concentration abruptly switches from
      low to high levels when transglutaminase activity exceeds a threshold value.
      Proteinase concentration usually follows the reverse complementary kinetics, but
      can become apparently uncoupled from extracellular matrix concentration for some
      parameter values. When matrix production by the cells and fragment degradation
      are taken into account, the dynamics change to sustained oscillations because of
      the emergence of a stable limit cycle. Transitions out of and into oscillation
      areas are controlled by the model parameters. Biological interpretation indicates
      that these oscillations could represent the normal homeostatic situation, whereas
      the other exhibited dynamics can be related to pathologies such as tumor invasion
      or fibrosis. These results allow to discuss the insights that the model could
      contribute to the comprehension of these complex biological events.

PMID- 12183136
TI  - On the size distribution of live genera.
AB  - This article deals with the theoretical size (number of species) distribution of
      live genera, arising from a simple model of macroevolution in which speciations
      and extinctions are assumed to occur independently and at random, and in which
      new genera are formed by the random splitting of existing genera. Mathematically,
      the distribution is that of the state of a homogeneous birth-and-death process
      after an exponentially distributed time. An ordinary differential equation for
      the generating function of the distribution is derived and solved and a
      recurrence relation for computing the probabilities in the distribution
      presented. Some properties of the distribution, including asymptotic behaviour,
      are examined and the distribution of the time since establishment of a genus of a
      given size derived. Fitting the distribution to empirical taxon size
      distributions by maximum likelihood is discussed and two examples are presented.

PMID- 12183138
TI  - Behaviours and rituals in the operating theatre. A report from the Hospital
      Infection Society Working Party on Infection Control in Operating Theatres.

PMID- 12183139
TI  - Water, water everywhere nor any a sterile drop to rinse your endoscope.
AB  - Traditional waterborne infections have been largely controlled in the UK by the
      provision of clean drinking water. However, water can still cause problems for
      infection control teams in particular when used in endoscope washer-disinfectors.
      HTM 2030 states that final rinse water used in washer-disinfectors must not
      present a microbiological hazard and that there should be no recovery of micro
      organisms from the final rinse water. The problems that biofilms may cause in
      washer-disinfectors, the type of biofilms that may develop, and the nature of the
      bacteria within them, in particular how biofilm bacteria behave differently to
      those that are not part of a biofilm (planktonic bacteria), are discussed in this
      article. Finally, we discuss how knowledge of the growth and control of biofilms
      may be used to control their growth.

PMID- 12183140
TI  - Comparative pulsed-field gel electrophoresis typing of gentamicin-resistant and 
      susceptible methicillin-resistant Staphylococcus aureus strains isolated in
      France between 1991 and 1998. Changes in antibiotic susceptibility.
AB  - Using macrorestriction of genomic DNA and pulsed-field gel electrophoresis, we
      examined 504 non-redundant, infection-causing human isolates of methicillin
      resistant Staphylococcus aureus susceptible (G(S): 238 isolates) or resistant to
      gentamicin (G(R): 266 isolates). The strains were isolated at Albert Chenevier
      Hospital (Creteil, France) between 1 January 1991 and 31 December 1998. Their
      susceptibility to erythromycin, lincomycin, tetracycline, rifampicin, fusidic
      acid and fosfomycin was also studied. Seventy-six genotypes were identified
      (percentage similarity<80). Ten types, each containing at least eight strains,
      predominated. G(R) strains showed higher genetic polymorphism than G(S) strains:
      the 266 G(R) isolates belonged to 67 genotypes, five of which predominated (44,
      42, 38, 30 and 15 isolates); the 238 G(S) isolates belonged to only 18 types,
      four of which predominated (112, 83, 11 and 10 isolates). Fifty-six percent of
      G(R) strains (34 Gt) were resistant to erythromycin, lincomycin, tetracycline and
      rifampicin, and were isolated at relatively stable frequencies. Resistance to
      five antibiotics studied (susceptible to fusidic acid) was observed among 16.5%
      of G(R) strains. The frequency of strains with this profile diminished from 30%
      in the early 1990s to 10% in 1998. One hundred and twenty-six G(S) isolates were
      susceptible to all six antibiotics; this profile was only found from 1993
      onwards, and was increasingly frequent (60% of G(S) strains in 1996). Resistance
      to erythromycin and lincomycin only was found in 70 G(S) isolates; this profile
      accounted for approximately half the isolates in 1992/1993 and only one-third in
      1998. These results, obtained over an eight-year period, show an overall increase
      in antibiotic susceptibility. They confirm the spread of two major clones of MRSA
      G(S) and support the hypotheses that G(S) strains derive from G(R) strains that
      have lost the aac6'-aph2" gene; and that G(S) strains are genetically related to
      those that were present before the use of gentamicin and persisted at a low
      frequency until 1992-1993.

PMID- 12183141
TI  - Evaluation of the efficacy of ultraviolet irradiation for disinfection of
      hospital water contaminated by Legionella.
AB  - We evaluated the efficacy of the ultraviolet irradiation on hospital water
      colonized by Legionella pneumophila serogroup 3, by inserting a lamp system on a
      hot water pipe supplying a small area. Cultures were performed for four months
      from 5L samples of water, collected before and after the ultraviolet treatment at
      the lamp unit and from two distal points. Irradiation was effective immediately
      after disinfection (<10 cfu/L), even when the incoming water was highly
      contaminated. One distal point showed little or no contamination (<10-20 cfu/L),
      while the other showed little to moderate contamination (<10(3) cfu/L). We
      conclude that ultraviolet irradiation is useful to protect the water system in
      small area; however, because of the lack of residual activity, it should be
      combined with other methods of disinfection. Maintenance of the water system is
      also necessary in order to reduce biofilm formation and Legionella
      recolonization.

PMID- 12183142
TI  - Clinical and epidemiological aspects of an enterovirus outbreak in a neonatal
      unit.
AB  - An outbreak of enterovirus infection occurred among neonates in a maternity
      hospital between July 7 and 22, 1999. Twenty neonates became ill (18 confirmed
      and two probable), an attack rate of 33%. The incubation period ranged from three
      to six days (mean, 4.2). The male:female ratio was 11:9 and the mean age at the
      onset of illness was 5.5 days. All the babies had fever, eight, a maculopapular
      rash, and six had symptoms of gastroenteritis, 11 developed meningitis. Nineteen
      neonates required hospitalization for three to seven days, but all were
      discharged home without sequelae. Enteroviral RNA was detected in all of 18
      urines, and 14 cerebrospinal fluid specimens tested. A case-control study was
      conducted to determine risk factors associated with the outbreak. Rooming in the
      nursery ward was a significant risk factor (odds ratio=33.35; 95% confidence
      interval, 3.79-800; P=0.00002). No association was found between illness and
      other possible risk factors. Appropriate control measures resulted in resolution
      of the outbreak. Our findings demonstrate the potential for enteroviruses to
      cause widespread illness among newborns, and emphasize the usefulness of
      polymerase chain reaction in the early diagnosis of infection, and underline the
      role of effective control measures in interrupting viral transmission.

PMID- 12183143
TI  - A determination of healthcare worker exposure to Mycobacterium tuberculosis in
      two Californian hospitals.
AB  - The US Centers for Disease Control and Prevention (CDC) recommends the prompt and
      sustained placement of potentially infectious tuberculosis patients in to
      negative-pressure isolation rooms, to help prevent other patients and workers,
      who remain outside of the room, from exposure to potential aerosols of
      Mycobacterium tuberculosis. The purpose of this study was to assess the potential
      for healthcare worker exposure to such aerosols and, to study compliance with the
      CDC guidelines. All room locations of culture-positive pulmonary TB patients were
      identified retrospectively for a one-year period at two hospitals. Placement in a
      negative-pressure isolation room was delayed for >24h after admission in 30% of
      54 patients at hospital 1, and for 56% of nine patients at hospital 2. The median
      delay in isolation was three days at hospital 1, and five days at hospital 2. At
      hospital 1, of the 16 patients with delayed or no isolation, 14 (88%) were AFB
      smear-positive, and 12 (75%) were admitted to the hospital during the winter
      months. At hospital 2, of five patients with delayed or no isolation, two (40%)
      were AFB smear-positive, and four (80%) were admitted to the hospital during the
      winter months. The main reason for non-isolation was failure to initiate and
      sustain isolation for all suspect tuberculosis patients during the winter. These
      delays may reflect an insufficient number of isolation rooms to accommodate an
      increased usage of isolation rooms during the winter months. Delays in suspecting
      tuberculosis also contributed to non isolation. For 33% of the non-isolated
      patients, recognition of the diagnosis was delayed for three or more days.
      Patients were hospitalized on most adult inpatient wards, and virtually every
      hospital location that had these patients also had, non-isolated sources of
      mycobacterial aerosol. All workers were at risk of exposure, although the risk
      varied by hospital location, and should be tuberculosis skin-tested, at least
      annually. Suspect and known tuberculosis patients should be isolated until they
      are demonstrated to be non-infectious.

PMID- 12183144
TI  - Epidemiology of invasive aspergillosis in France: a six-year multicentric survey
      in the Greater Paris area.
AB  - Invasive aspergillosis is the most prevalent mould infection. An epidemiological
      surveillance network was set up in 18 teaching hospitals in Paris and the Greater
      Paris area. Prospective surveillance was conducted between 1994 and 1999. Between
      1994 and 1997 cases were categorized as proven or probable aspergillosis and then
      the European Organization for Research and Treatment of Cancer/Mycoses Study
      Group criteria were used. The authors analysed 621 cases (115 proven, 506
      probable). No seasonal variation was found. Haematological disorders (73%)
      including stem-cell transplantation (36%), solid-organ transplantations (10%) and
      AIDS (9%) were the main underlying conditions. The crude mortality was 63%.
      Incidence of IA was 8% (CI(95): 6.5-9.5) in acute myelocytic leukaemia and 6.3%
      (CI(95): 4.3-8.3) in acute lymphocytic leukaemia. Incidence was 12.8% (CI(95):
      10.8-14.8) following allogeneic stem-cell transplantation and 1.1% (CI(95): 0.7
      1.5) following autologous stem-cell transplantation. In solid-organ recipients
      incidence ranged from 11% following heart-lung transplantation and small bowel to
      0.4% following kidney transplantation. Incidence in HIV infected patients ranged
      from 0.02 to 0.13% per annum. This large series confirmed that patients with
      haematologic disorders and transplantations are the most at risk for IA.

PMID- 12183145
TI  - European Confederation of Medical Mycology (ECMM) prospective survey of
      candidaemia: report from one Italian region.
AB  - An ECMM epidemiological prospective survey of candidaemia was performed in one
      Italian region (Lombardy; population: 8 924 870) by the National Society of
      Medical Mycology (FIMUA) from September 1997 to December 1999. In total, 569
      episodes were reported with an overall rate of 0.38/1000 admissions, 4.4/100000
      patient days. Predisposing factors included presence of an intravascular catheter
      (89%), antibiotic treatment (88%), surgery (56%), intensive care (45%), solid
      tumour (28%), steroid treatment (15%), haematological malignancy (7%), HIV
      infection (6%), fetal immaturity (4%). Mucous membrane colonization preceded
      candidaemia in 83% of patients. Candida albicans was identified in 58% of cases,
      followed by Candida parapsilosis (15%), Candida glabrata (13%), Candida
      tropicalis (6%). Septic shock occurred in 95 patients. Crude mortality was 35%,
      the highest in C. tropicalis fungaemia (44%), the elderly (64%) and solid tumour
      cancer patients (43%). Intravascular catheter removal was associated with higher
      survival rate (71 vs. 47%). This survey underscores the importance of candidaemia
      in hospital settings.

PMID- 12183146
TI  - Use of 2% 2-phenoxyethanol and 0.1% octenidine as antiseptic in premature newborn
      infants of 23-26 weeks gestation.
AB  - In preterm newborn infants, topical iodine-containing antiseptics disturb thyroid
      hormone regulation while alcohol-based disinfectants may cause local burns. We
      therefore investigated the use of an aqueous solution containing 0.1% octenidine
      and 2% 2-phenoxyethanol for skin disinfection during the first seven days of life
      in premature newborns with a gestational age <27 weeks who were consecutively
      admitted to our level III neonatal intensive care unit between November 1, 2000
      and December 31, 2001 (N=24). In boys. (N=13) the renal excretion of absorbed 2
      phenoxyethanol and its metabolite 2-phenoxyacetic acid was quantitated by high
      pressure liquid chromatography. In the most immature newborn (gestational age 23
      6/7 weeks), a transient erythematous reaction was observed following application
      of the octenidine/phenoxyethanol solution prior to umbilical vessel
      catheterization. No other local reactions were observed. The urinary
      concentration of 2-phenoxyethanol was <2 ppm in all samples, while urinary 2
      phenoxyacetic acid concentrations reached 5-95 ppm (median 24 ppm). One infant
      had a culture-proven septicaemia (Bacillus species) during the first seven days
      of life. We conclude that, in contrast to alcohol-based antiseptics, an aqueous
      solution of 0.1% octenidine and 2-phenoxyethanol does not cause major skin damage
      in premature newborn infants <27 weeks' gestation. 2-Phenoxyethanol is readily
      absorbed by the newborn's skin but apparently undergoes extensive oxidative
      metabolization to 2-phenoxyacetic acid.

PMID- 12183147
TI  - Should we routinely disinfect floors?

PMID- 12183149
TI  - Recommendations for surgical hand disinfection -- requirements, implementation
      and need for research. A proposal by representatives of the SFHH, DGHM and DGKH
      for a European discussion.

PMID- 12183151
TI  - Opportunities and obstacles in developing a vaccine for Entamoeba histolytica.
AB  - The development of a vaccine against Entamoeba histolytica, the causative agent
      of amebic colitis and liver abscess, would reduce childhood mortality in
      countries such as Bangledesh where community-based studies have demonstrated a
      high prevalence of E. histolytica. Immunological studies from this population
      have shown that protection from amebiasis is associated with mucosal anti-E.
      histolytica Gal/GalNAc lectin antibodies, suggesting that a vaccine is an
      achievable goal. However, garnering resources for vaccine development is a
      challenge when the vaccine is targeted to poor people living in developing
      countries.

PMID- 12183152
TI  - Challenges for the development of vaccines against Haemophilus influenzae and
      Neisseria meningitidis.
AB  - The development of protein-polysaccharide conjugate vaccines has had a major
      impact on Haemophilus influenzae type b disease. The application of this
      technology to Neisseria meningitidis is also striking, particularly for serogroup
      C. However, significant challenges exist for the development of vaccines against
      non-typeable H. influenzae and against N. meningitidis serogroup B. Issues such
      as non-vaccine-strain replacement and correlates of protection need to be
      addressed as well as the longer-term implications of vaccination against what are
      essentially 'normal' microflora.

PMID- 12183153
TI  - Transplantation.

PMID- 12183154
TI  - Chemokines: directing leukocyte infiltration into allografts.
AB  - Chemokines have been shown to play a critical role in the recruitment of
      leukocytes to transplanted organs. Animal models and clinical studies have
      demonstrated predictable temporal and spatial correlations between chemokine
      production and leukocyte infiltration into allografts. Antagonism of chemokines
      or chemokine receptors has been shown to delay leukocyte infiltration and prolong
      graft function, demonstrating an important role for chemokines in allograft
      rejection.

PMID- 12183156
TI  - Late deterioration of organ transplants: a problem in injury and homeostasis.
AB  - The late deterioration of allografts remains a problem despite improvements in
      short-term and long-term graft survival. The previous concept that late
      deterioration reflects a specific disease -- chronic rejection -- is being
      replaced. The new view is that many factors are involved in late deterioration,
      including the age and pretransplant condition of the organ, injury from brain
      death, injury from the transplant process, T cell-mediated and antibody-mediated
      rejection (in some cases reflecting poor compliance with immunosuppressive drugs)
      and post-transplant organ-specific stresses in the new environment, including
      drug toxicity, infectious agents, hypertension and lipids. Ultimately these
      stresses interact with the intrinsic limitations in repair and homeostasis in the
      tissues of the organ, producing characteristic syndromes. The most important
      recent advance has been the emergence of potent immunosuppressive drug
      combinations that have greatly reduced rejection.

PMID- 12183155
TI  - FTY720: targeting G-protein-coupled receptors for sphingosine 1-phosphate in
      transplantation and autoimmunity.
AB  - The novel immunomodulator FTY720 is remarkably effective in models of
      transplantation and autoimmunity. Recent data show that phosphorylated FTY720 is
      an agonist at four sphingosine 1-phosphate receptors. Stimulation of sphingosine
      1-phosphate receptors leads to sequestration of lymphocytes in secondary
      lymphatic tissues and thus away from inflammatory lesions and graft sites.

PMID- 12183157
TI  - Regulatory T cells in transplantation.
AB  - There has recently been an explosion of renewed interest in regulatory T cells,
      particularly those within the CD4(+)CD25(+) population. It is becoming
      increasingly apparent that these cells exist not only as naturally occurring
      cells that may contribute to the maintenance of self-tolerance, but they also
      have the potential to prevent rejection of allografts in experimental models.
      Such cells have now been identified in humans as well as in rodents.

PMID- 12183158
TI  - Mechanisms of transplant tolerance induction using costimulatory blockade.
AB  - The potential use of costimulation-blocking reagents to induce transplantation
      tolerance has recently created considerable excitement. Recent evidence has begun
      to delineate the mechanisms by which these powerful effects occur. It has become
      increasingly clear, firstly, that T cell costimulation is mediated by a delicate
      network of signaling pathways and, secondly, that interference with these systems
      can lead to numerous different tolerance mechanisms, including immune regulation,
      anergy and deletion.

PMID- 12183159
TI  - Allogeneic stem cells, clinical transplantation and the origins of regenerative
      medicine.
AB  - The therapeutic use of stem cells is a popular topic that is often in the news.
      Stem cells are of particular relevance to the transplant community, as stem cell
      based therapies will probably be derived from allogeneic sources. Stem cells may
      be obtained from somatic (adult) cell or embryonic cell origin. The ability to
      establish stem cell lines in vitro means that we can standardize therapeutic
      grafting applications, which is a prerequisite for the widespread application of
      stem cell therapy. This attribute also means that we can produce large batches of
      allogeneic terminally differentiated cells, which can be administered to
      patients. Three important barriers to the deployment of this therapy currently
      exist; in addition to the many ethical issues facing the widespread use of stem
      cell therapy, it is also important to develop methods to derive pure terminally
      differentiated cells for transplantation and to induce immune tolerance to these
      allogeneic cells, as daily anti-rejection therapy cannot be justified for many
      potential applications.

PMID- 12183161
TI  - Disease consequences of pathogen adaptation.
AB  - Experimental evolution studies demonstrate that pathogens evolve rapidly, have a
      large capacity for increased virulence and cause disease in many different ways.
      A large proportion of genetic diversity for host susceptibility to infectious,
      autoimmune and 'genetic' diseases, and to cancer, is probably caused by pathogens
      and/or host counteradaptations. Recent advances in diverse fields support this
      claim and suggest many underused approaches for identifying and experimentally
      dissecting the complicated host-pathogen interactions that often lead to disease.

PMID- 12183162
TI  - Variable receptors controlling activation and inhibition of NK cells.
AB  - NK cells are important effector lymphocytes of innate immunity; they kill
      infected cells and produce cytokines that stimulate other immune effects. Once
      considered relatively homogeneous, NK cells are now seen to be highly diverse.
      Within an individual, expression of different combinations of inhibitory and
      stimulatory receptors creates a diverse NK cell repertoire, which exhibits
      specificity in the immune response. Rapid evolution of NK cell receptor gene
      families distinguishes members of a species and causes substantial species
      specific differences in NK cell receptor systems. All known ligands for these
      diverse receptors are MHC class I molecules, or molecules of host or pathogen
      origin that are homologous to MHC class I.

PMID- 12183163
TI  - Analyzing genomes: current realities and future possibilities.
AB  - The rapidly developing databases of genomic sequences of human and model
      organisms herald the beginning of a new era in genetic analysis. New, genome
      based technologies are revealing important details in the structure and
      diversification of mammalian genomes and are fundamentally changing the field of
      genetics. In the future, genomic analysis will become a standard tool of
      geneticists and has the potential to revolutionize the field of immunogenetics.

PMID- 12183164
TI  - Gene-expression profiling and the genetic dissection of complex disease.
AB  - Several recent studies have highlighted how combining the powerful techniques of
      microarray analysis and congenic-strain analysis may greatly facilitate
      unravelling the genetic basis of susceptibility to common autoimmune diseases. In
      addition to providing pointers to the genetic variants themselves, the pathway(s)
      they control may also be highlighted, thereby identifying new targets for
      therapeutic intervention.

PMID- 12183166
TI  - Novel vaccines protecting against the development of allergic disorders: a double
      edged sword?
AB  - The severity and incidence of allergic disorders is steadily increasing despite
      the widespread use of steroids and other drugs. Recent results obtained in
      animals suggest that it may be possible to develop novel anti-allergy vaccines
      for human use, thereby stopping this alarming worldwide increase in allergic
      diseases. The most promising approaches are the induction of allergen-specific T
      helper 1 or allergen-specific T regulatory responses. However, both approaches
      potentially harbour negative side effects that need to be ruled out before
      vaccinating young children -- the best candidates for the primary prevention of
      allergic disorders.

PMID- 12183167
TI  - Allergy immunotherapy and inhibition of Th2 immune responses: a sufficient
      strategy?
AB  - Th2 immune responses mediated by the secretion of IL-4, IL-5 and IL-13 are key in
      the pathogenesis of atopic disorders, including allergen-induced asthma,
      rhinoconjunctivitis and anaphylaxis. Although such responses are downregulated to
      some degree by conventional specific immunotherapy, this approach is only
      partially effective and has a substantial risk of adverse effects. Many
      strategies for immunotherapeutic prophylaxis and for treatment of atopic diseases
      have been devised on the basis of mouse allergy and autoimmune models, including
      the downregulation of Th2 responses by the induction of regulatory T cell
      activity, Th2 to Th1 immune deviation, Th1 crossregulation of Th2 immune
      responses, anergy and immunosuppressive cytokines. The blockade of events that
      are not allergen-specific, such as T cell costimulation and downstream events
      dependent on IgE, cytokines and chemokines, has also been pursued. With the
      exception of monoclonal antibody therapy for the blockade of IgE effector
      function, the application of most of these strategies to humans is at an early
      stage. Whether the inhibition of Th2 responses without concurrent downregulation
      of Th1 responses will be sufficient for allergic immunotherapy, particularly for
      atopic dermatitis and asthma, is an important but unresolved issue.

PMID- 12183168
TI  - Immunotherapy of insulin-dependent diabetes mellitus.
AB  - Type 1 diabetes mellitus is caused by the T cell mediated autoimmune destruction
      of insulin-producing beta cells of the islets of Langerhans within the pancreas.
      Current immunotherapy strategies are aimed at directly inactivating the
      autoreactive T cells and/or inducing T cells with regulatory capabilities. At the
      preclinical level, several strategies that employ TCR antagonists -- including
      monoclonal antibodies, autoantigen-specific peptides and soluble TCR ligands --
      are showing promise and being developed for clinical application. Several of
      these approaches employing monoclonal antibodies against the TCR-CD3 complex or
      soluble peptide antigens are producing favorable results in the clinic.

PMID- 12183169
TI  - Immunotherapy as a means to induce transplantation tolerance.
AB  - There have been several recent advances in the use of immunotherapy to induce
      transplantation tolerance. These include newer and safer protocols to create
      hematopoietic chimerism, the development of more-powerful T cell depleting
      antibodies, the identification of additional costimlulatory pathways as molecular
      targets and the identification of a role for suppressor cells in transplant
      tolerance.

PMID- 12183170
TI  - Recent advances in mucosal vaccines and adjuvants.
AB  - Mucosal vaccines may be used both to prevent mucosal infections through the
      activation of antimicrobial immunity and to treat systemic inflammatory diseases
      through the induction of antigen-specific mucosal tolerance. New, efficient
      mucosal adjuvants for human use have been designed based on, amongst others,
      bacterial toxins and their derivatives, CpG-containing DNA, and different
      cytokines and chemokines, with the aim of improving the induction of mucosal Th1
      and Th2 responses. Mucosal delivery systems, in particular virus-like particles,
      have been shown to enhance the binding, uptake and half-life of the antigens, as
      well as target the vaccine to mucosal surfaces. DNA vaccines are currently being
      developed for administration at mucosal surfaces. However, there have also been
      failures, such as the withdrawal of an oral vaccine against rotavirus diarrhea
      and a nasal vaccine against influenza, because of their potential side effects.

PMID- 12183174
TI  - The role of GA-mediated signalling in the control of seed germination.
AB  - Seed germination is promoted by gibberellin (GA) in many plant species. Several
      GA signalling factors are known to induce the expression of genes encoding
      enzymes that mobilise food reserves, including starches, proteins and lipids,
      stored in the endosperm during seed germination. However, these factors do not
      control seed germination. Two recent reports have indicated that RGL1 and RGL2,
      both homologous to the GA-response height-regulating factors
      GAI/RGA/RHT/d8/SLR1/SLN1, are repressors of seed germination in Arabidopsis.
      These reports provide new clues as to how GA controls seed germination. The
      induction of RGL2 expression by imbibition and its repression by GA are of
      particular interest because they imply that RGL2 acts as an integrator of
      environmental and endogenous cues for germination.

PMID- 12183175
TI  - Peptide signalling in plants.
AB  - Peptide signals play crucial roles in all aspects of the plant life cycle. An
      understanding of peptide signal production and reception mechanisms is beginning
      to emerge. Studies on the signal-transduction cascades that follow the reception
      of peptide signals are just beginning.

PMID- 12183176
TI  - Hydrogen peroxide signalling.
AB  - Recent biochemical and genetic studies confirm that hydrogen peroxide is a
      signalling molecule in plants that mediates responses to abiotic and biotic
      stresses. Signalling roles for hydrogen peroxide during abscisic-acid-mediated
      stomatal closure, auxin-regulated root gravitropism and tolerance of oxygen
      deprivation are now evident. The synthesis and action of hydrogen peroxide appear
      to be linked to those of nitric oxide. Downstream signalling events that are
      modulated by hydrogen peroxide include calcium mobilisation, protein
      phosphorylation and gene expression. Calcium and Rop signalling contribute to the
      maintenance of hydrogen peroxide homeostasis.

PMID- 12183177
TI  - Role of the extracellular matrix in cell-cell signalling: paracrine paradigms.
AB  - The plant extracellular matrix (ECM) is complex and diverse, and is involved in
      cell-cell communication in a wide range of developmental, reproductive and
      pathogenic processes. Characterisation of integral ECM components is leading to
      improved understanding of their roles in signalling. Interactions between the
      extracellular domains of plant plasma membrane receptor kinases and their ligands
      are potentially regulated by the properties of the ECM. Several of these
      interactions, for example those involving the S-locus receptor kinase, are being
      characterised in some detail. Non-protein constituents are also implicated in
      regulating the movement of signalling molecules in the ECM, which is associated
      with developmental patterning. In contrast to the situation in animal cells,
      cytoskeleton-integrin-ECM signalling complexes appear not to be dominant features
      of signal transduction in plant cells. Nevertheless, structural adhesions between
      the plasma membrane and cell wall are important for a variety of functions.

PMID- 12183178
TI  - G-protein-coupled signaling in Arabidopsis.
AB  - With an essentially complete plant genome in hand, it is now possible to conclude
      that a single or possibly just two canonical heterotrimeric G-protein complexes
      are present in Arabidopsis. In stark contrast, more than one hundred such
      complexes are found in some metazoans. Nonetheless, it appears that
      heterotrimeric G-protein complexes couple or affect many different signaling
      pathways in plants. In addition, there are very few, if any, candidate G-protein
      coupled receptors through which this single complex can couple to downstream
      effectors. Furthermore, some of the classical downstream effectors that are
      activated by heterotrimeric G proteins in metazoans are also lacking in plants.
      Thus, we are left with the urgent challenge to determine the novel mechanism of G
      protein signaling in plant cells. Recent advances using reverse and molecular
      genetic approaches have re-opened this topic for plant biologists and the
      resulting tools will accelerate our progress.

PMID- 12183179
TI  - Phospholipase D in hormonal and stress signaling.
AB  - Phospholipase D (PLD) is a family of diverse enzymes that are differentially
      regulated by Ca(2+), polyphosphoinositides, free fatty acids, G-proteins, N
      acylethanolamines, and membrane lipid environments. Two new types of PLDs were
      identified in the past year: one is activated by oleic acid and the other
      requires no cation for activity. The oleate-stimulated PLD is associated with the
      plasma membrane and binds to microtubules. The Ca(2+)-independent PLD contains a
      PX and a PH domain, but not the Ca(2+)/phospholipid-binding C2 domain found in
      most plant PLDs. The mechanism by which Ca(2+), phosphoinositides, and G proteins
      regulate certain PLDs is better understood. PLDs and their product phosphatidic
      acid are involved in various stress responses, including water deficits, salts,
      wounding, and elicitation. Increasing evidence supports a role of PLD in the
      abscisic acid signaling cascades.

PMID- 12183180
TI  - Complexity, cross talk and integration of plant MAP kinase signalling.
AB  - Mitogen-activated protein kinases (MAPKs) link information transfer from external
      stimuli-activated sensors to cellular responses. The completed Arabidopsis genome
      sequence revealed an extraordinary complexity in MAPK-signalling components in
      plants. Information obtained from Arabidopsis provides a framework for a unified
      nomenclature and the assembly and function of MAPK-signalling pathways.
      Strategies and tools are evolving to connect MAPK pathways and to determine their
      function. As a result, MAPK signalling modules emerged, one of which appears to
      antagonistically regulate stress- and growth-responses and another that regulates
      cytokinesis.

PMID- 12183181
TI  - Cyclic nucleotides: the current dilemma!
AB  - Significant advances in understanding plant cyclic nucleotide signalling have
      been made in the past two years. The roles of these molecules in the regulation
      of ionic channels, defence responses and the apical growth of cells are being
      uncovered.

PMID- 12183182
TI  - Transcription factors in plant defense and stress responses.
AB  - Transcriptional control of the expression of stress-responsive genes is a crucial
      part of the plant response to a range of abiotic and biotic stresses. Research
      carried out in the past few years has been productive in identifying
      transcription factors that are important for regulating plant responses to these
      stresses. These studies have also revealed some of the complexity and overlap in
      the responses to different stresses, and are likely to lead to new ways to
      enhance crop tolerance to disease and environmental stress.

PMID- 12183183
TI  - Acetylated, methylated, remodeled: chromatin states for gene regulation.
AB  - The activity state of a gene is determined not only by sequence-specific
      regulatory factors but also by a complex network of co-acting proteins. Many of
      these proteins directly or indirectly affect the structure of the chromatin
      environment into which the gene is embedded. Recent studies of histone and DNA
      modifications support and refine the concept of the chromatin environment being
      key to the establishment and maintenance of transcriptional activity or
      repression.

PMID- 12183184
TI  - RNA silencing: small RNAs as ubiquitous regulators of gene expression.
AB  - 'RNA silencing' is the suppression of gene expression through nucleotide sequence
      specific interactions that are mediated by RNA. Initially identified as an immune
      system that is targeted against transposons and viruses, RNA silencing is
      emerging as a fundamental regulatory process that is likely to affect many layers
      of endogenous gene expression in most, if not all, eukaryotes.

PMID- 12183185
TI  - RNA-binding proteins in plants: the tip of an iceberg?
AB  - RNA-binding proteins, which are involved in the synthesis, processing, transport,
      translation, and degradation of RNA, are emerging as important, often
      multifunctional, cellular regulatory proteins. Although relatively few RNA
      binding proteins have been studied in plants, they are being identified with
      increasing frequency, both genetically and biochemically. RNA-binding proteins
      that regulate chloroplast mRNA stability and translation in response to light and
      that have been elegantly analyzed in Clamydomonas reinhardtii have counterparts
      with similar functions in higher plants. Several recent reports describe
      mutations in genes encoding RNA-binding proteins that affect plant development
      and hormone signaling.

PMID- 12183186
TI  - Regulation of translational initiation in plants.
AB  - The abundance of cytosolic mRNA does not necessarily correspond to the quantity
      of polypeptide synthesized in plant cells. The initiation of mRNA translation is
      regulated at the global and message-specific levels. mRNAs compete for
      discriminatory initiation factors that couple the 5'-(7m)GpppN-cap and the 3'
      poly(A) tail of the RNA message. The resultant circularization of the mRNA
      promotes the association of the 43S pre-initiation complex that scans the 5'
      leader for the initiation codon of the protein coding sequence. The physiological
      and developmental regulation of these events governs the level of polypeptide
      synthesis from endogenous and viral transcripts.

PMID- 12183187
TI  - A perfusion technique for the determination of pro-inflammatory mediators induced
      by intradental application of irritants.
AB  - INTRODUCTION: Several morphological and functional features contribute to the
      consideration of the tooth as a separate compartment having special type of
      innervation and special immune mechanisms. This study describes a new method
      allowing the intradental perfusion of rat incisors for the in vivo assessment of
      pulpal reaction to inflammatory agents. METHODS: Under deep anesthesia, the
      distal 2-3 mm of each of the rat lower incisors was cut and wrapped in a
      polyethylene tubing connected to a perfusion chamber made of tigone tubing (ID
      1/8 in., volume 100-150 microl). Several groups of rats (n=5 each) were used for
      intradental application of either saline, capsaicin (100 microg in 100 microl),
      or endotoxin (ET, 20 microg in 100 microl) for a period of 40 min followed by
      filling the tooth chamber with saline and collecting the perfusate every 40 min
      for a period of 8 h. The collected perfusates were stored at -70 degrees C for
      subsequent determination of the concentration of prostaglandin E(2) (PGE(2)) and
      nerve growth factor (NGF) by enzyme-linked immunosorbent assay (ELISA). RESULTS:
      Dentinal injury produced a moderate increase in the levels of NGF and PGE(2) in
      incisors perfused with saline. Application of ET or capsaicin, however, produced
      a highly significant increase in the levels of both mediators. These effects
      peaked at 1.5-3 h for PGE(2) and at 5 h for NGF. Capsaicin showed the most
      significant effects. DISCUSSION: The reported results cannot be attributed to any
      factor other than the inflammation of the incisor's pulp, because the described
      chamber does not allow any spread or leak of the applied irritants. Further
      studies using other reagents can allow the determination of the variation of the
      levels of the various pro-inflammatory mediators and their modulation by
      treatment with anti-inflammatory drugs.

PMID- 12183188
TI  - Simultaneous determination of mepivacaine, tetracaine, and p-butylaminobenzoic
      acid by high-performance liquid chromatography.
AB  - INTRODUCTION: The purpose of the present study was to develop a simple method for
      the simultaneous determination of mepivacaine, tetracaine, and p
      butylaminobenzoic acid (BABA) in human plasma using high-performance liquid
      chromatography (HPLC) with a multiwavelength detector. METHODS: Human blood
      samples containing heparin, as an anticoagulant, and physostigmine (100
      microg/ml), as an anticholinesterase, or human plasma containing physostigmine
      were spiked with various concentrations of mepivacaine, tetracaine and, in some
      cases, BABA. Blood samples were centrifuged and plasma was deproteinized with
      trifluoroacetic acid (TFA; 7%). After centrifugation, the pH was adjusted to 4.5
      and an aliquot of 20, 50 or 100 microl was injected into the HPLC apparatus. The
      detection was done simultaneously at wavelengths of 214 and 300 nm. Analytical
      chromatography was done on a Waters microBondapak C(18) reverse-phase column (3.9
      x 300 mm; particle size 10 microm) with a 30-min increasing linear gradient of 20
      40% acetonitrile+0.05% TFA in H(2)O+0.05% TFA at a flow rate of 1 ml/min. The
      Waters HPLC system included two pumps, an automatic injector, a column oven, and
      a M490 multiwavelength detector. Quantification was done using integration of
      peak areas with peaks of authentic mepivacaine, tetracaine, and BABA standards.
      RESULTS: Calibration curves for standards of mepivacaine, tetracaine, and BABA
      were linear in the concentration ranges from 0.1 to 100 microg/ml, and the
      correlation coefficients exceeded.99 for all compounds. The lower limits of
      detection were 100 ng/ml for mepivacaine and 50 ng/ml for tetracaine and BABA.
      The yields for mepivacaine, tetracaine, and BABA were 91+/-2.1%, 82+/-3.3%, and
      88+/-2.0% (mean+/-S.E.M., n=6), respectively. Degradation of tetracaine by human
      plasma at 37 degrees C was inhibited by physostigmine. DISCUSSION: The method is
      sensitive enough to allow blood concentration determinations of mepivacaine and
      tetracaine or its metabolite, BABA, following local anesthesia induced by these
      two drugs, especially when their toxic effect may be present. This method also
      may be useful in forensic medicine for determination of the cause of death after
      local anesthesia with mepivacaine and/or tetracaine.

PMID- 12183189
TI  - Validation of a new computerized system for recording and analysing drug-induced
      tremor in rats.
AB  - INTRODUCTION: Certain drugs can induce tremor in small animals and can be used as
      Parkinson's disease or essential experimental tremor models. However, the use of
      arbitrary scales for evaluating tremor in experimental models is limited by
      observer subjectivity. Progress in electronics and computer science has allowed a
      more precise quantification of tremor. The objective of the present study was to
      validate a newly developed low-cost method of spectral registration and analysis
      of tremor in free-moving rats. METHODS: Male Wistar rats, 3-4 months of age,
      previously placed for 5 min inside a sensor cage, were administered with
      different doses of eserine (0.25-1.5 mg/kg), oxotremorine (0.25-1.5 mg/kg) or
      harmaline (7.5-60 mg/kg). Drug-induced tremor was recorded during 10 min using a
      computerized system composed of force transducers, a signal conditioning circuit,
      a digitizing interface and a microcomputer. The signal transmitted to the
      computer was quantified, stored and analyzed for its amplitude and frequency by
      means of specific programs. RESULTS: Tremor was induced with an amplitude that
      was dose-dependent for all drugs used. Tremor frequency was dose-dependent for
      oxotremorine and eserine, but not for harmaline. The performance of the system
      was compared with that of other systems described in behavioral instrumentation
      literature. DISCUSSION: The present data indicate that the new system is capable
      of detecting the tremor induced by drugs, and that the programs used for spectral
      analysis allow the quantification of the amplitude and the frequency of the
      tremor in free-moving rats.

PMID- 12183190
TI  - Characterisation of a modified approach to the study of sympathetic
      neurotransmission and its presynaptic modulation in the isolated rabbit thoracic
      aorta.
AB  - INTRODUCTION: The quantification of [(3)H]noradrenaline spillover from
      electrically stimulated, sympathetic nerves is a widely used method to study
      presynaptic effects of hormones, transmitters and drugs. Although a
      straightforward approach, the execution of the experiments is not trivial. This
      holds true mainly for a reliable control of the experimental conditions, a major
      pitfall of the commonly used superfusion setup, and problems concerning the
      sampling of the tritium containing probes. METHODS: These difficulties prompted
      us to develop a variant of this method, which is based on a classical organ bath
      setup. Rabbit thoracic aortic rings were incubated with [(3)H]-labeled
      noradrenaline. Instead of being constantly washed away by superfusion, the
      [(3)H]noradrenaline is allowed to accumulate in the medium. RESULTS: Electrical
      field stimulation (EFS) (2 Hz, 3 ms, 150 mA) caused a significant increase of
      [(3)H]noradrenaline outflow by approximately a factor 4.2 (P<.05). The fractional
      release of noradrenaline during consecutive periods of stimulation remained
      unaltered (FR(2)/FR(1) 0.99+/-0.03). The EFS-evoked release could be nearly
      abolished by the selective sodium channel blocker tetrodotoxin (1 microM)
      (FR(2)/FR(1) 0.06+/-0.03, P<.05). The N-type calcium antagonist omega-conotoxin
      GVIA (0.3 microM) abolished the stimulation-evoked outflow (FR(2)/FR(1) 0.01+/
      0.06, P<.05), whereas the antisympathotonic agent guanethidine (10 microM)
      attenuated the EFS-evoked noradrenaline outflow by approximately a factor 2
      (FR(2)/FR(1) 0.46+/-0.07, P<.05). Angiotensin II (0.1 and 1 nM) enhanced the EFS
      evoked [(3)H]noradrenaline outflow by nearly a factor 1.5 and 2, respectively
      (FR(2)/FR(1) of 1.43+/-0.11 (0.1 nM) and 2.03+/-0.11 (1 nM); n=6-8, P<.05). All
      agents failed to influence basal outflow. DISCUSSION: Our modified experimental
      approach appears to be suitable to study presynaptic influences on sympathetic
      transmission in the rabbit thoracic aorta. In addition to optimal control of the
      experimental conditions, the method offers the advantage of a safe and reliable
      sampling.

PMID- 12183192
TI  - The isolated perfused liver. a new model using autologous blood and porcine
      slaughterhouse organs.
AB  - INTRODUCTION: Current models of isolated and perfused livers are limited by
      nonphysiologic perfusates or the need for the use of high numbers of laboratory
      animals. The present study was performed in order to rectify these difficulties.
      METHODS: To establish a new isolated perfused liver model, a perfusion circuit
      was developed using normothermic, autologous hemoperfusion and organs obtained
      from a slaughterhouse. RESULTS: Stable organ function was maintained over 220
      min. The organs displayed physiologic values for measured variables, including
      oxygen consumption which varied from 5.2+/-1.5 ml/min at 40 min to 5.2+/-2.4
      ml/min at 220 min, and bile production (0.15-0.31 ml/min, respectively).
      DISCUSSION: The present studies demonstrate a new approach for experimental liver
      perfusion by combining the optimal perfusion medium of autologous blood and
      slaughterhouse organs as source material.

PMID- 12183191
TI  - A robust method for evaluation of NANC transmission in human sigmoid colon muscle
      in vitro.
AB  - INTRODUCTION: Human tissues are notoriously difficult to work with, giving
      results that are quantitatively variable within and between studies. Hence,
      previous investigations of nonadrenergic, noncholinergic (NANC) relaxation in
      human colon muscle report both partial and complete inhibitions of the NANC
      response by specific competitive inhibitors of nitric oxide (NO) production. We
      have established a robust and reproducible model to examine the contribution of
      NO during NANC relaxation assay in human sigmoid colon muscle strips. METHODS:
      Complete control curves to long-train, stepwise, frequency-dependent, continuous
      electrical field stimulation (EFS) relaxation using vertical platinum electrodes
      connected to a biphasic pulse train stimulator generated NANC responses in fresh
      human sigmoid colon circular muscle strips set up in Bennett baths. A second
      complete curve was generated on the same strip in the presence of specific drugs
      to determine the contribution of NO to NANC relaxation. Responses to NO were also
      generated in muscle strips. Results were fitted to the Hill equation. RESULTS:
      The first and second frequency-response curves without test drugs could be fitted
      to the Hill equation, resulting in similar midpoint locations ([f](50)), maximal
      asymptotes (alpha), and midpoint slope (n) parameters. L-N(G)-nitro-arginine (L
      NOARG), TTX, and haemoglobin produced a tonic contraction in the muscle strips.
      NANC relaxations to EFS were inhibited by L-NOARG (30-37%), TTX (56-62%), and
      haemoglobin (48-90%). NO relaxations were concentration dependently inhibited by
      haemoglobin. Haemoglobin was equipotent in mediating tonic contraction and
      inhibiting NO relaxation. DISCUSSION: We established reproducible assays for
      human colon muscle strips by the generation of two complete dose-response curves
      to long-train EFS, thus enabling a "within-preparations" study. The results
      suggest that NO contributes but is not the sole mediator of relaxations to long
      train EFS in human sigmoid colon muscle. Moreover, a basal production of NO may
      serve to regulate tone of human colonic muscle.

PMID- 12183193
TI  - An improvement of the Ames test using a modified human liver S9 preparation.
AB  - INTRODUCTION: In preliminary studies on the Ames test using human liver S9
      fractions, we found that the crude human S9 fractions, obtained following
      centrifugation of the tissue homogenate for 20 min at 9000 x g, were not always
      sterile. When this was the case, the S9 fractions were often accompanied by an
      increased number of colonies above the normal range on plates in the solvent
      control used in the Ames test. In addition, we also sometimes identified the
      incorporation of a small amount of fat in the crude human liver S9 fractions. We
      have therefore obtained a purified fat-free S9 fraction by a simple modification
      to the crude S9 preparation; fat was completely removed by centrifugation of the
      crude S9 fraction. METHODS: Using the purified and crude human S9 fractions (two
      lots each), both the sterility and the number of bacterial colonies produced on a
      plate with five bacterial tester strains by solvent controls (purified water and
      dimethyl sulfoxide) were examined. The findings were then compared to those
      observed with phosphate buffer or S9 fraction from rats pretreated with
      phenobarbital/5,6-benzoflavone. RESULTS: The data show that each of the crude
      human S9 fractions was not sterile and produced an increasing number of colonies
      with each solvent control, almost equal to the sum of the numbers of
      contaminating bacterial colonies and spontaneous revertant colonies observed with
      phosphate buffer or the rat S9 fraction. On the other hand, both the purified
      human S9 fractions were sterile, and the number of colonies that appeared in each
      solvent control was similar to that of spontaneous revertant colonies observed
      with phosphate buffer or the rat S9 fraction. DISCUSSION: These results indicate
      that this new procedure of S9 preparation, modified with an additional
      recentrifugation step, may provide a high quality of purified fat- and bacteria
      free S9 fraction for use in the Ames test.

PMID- 12183194
TI  - A problem with Hebb and local spikes.
AB  - Although our understanding of the cellular properties of mammalian neurons is
      increasing rapidly, the computational function of their elaborate dendritic trees
      is still mysterious. In recent years, experiments have shown that, in pyramidal
      cells, individual dendritic compartments sustain local excitation spikes.. These
      dendrites also support Hebbian synaptic plasticity, which depends on the precise
      temporal relationship between pre- and postsynaptic spikes. In this review we
      discuss what we consider to be a problem with Hebbian (i.e., spike-timing
      dependent) plasticity. We argue that most of the spikes that occur in dendrites
      are not back-propagating action potentials but but local spikes, and that Hebbian
      plasticity caused by local spikes can undermine the functional integrity of the
      geometrically complex dendritic tree. We propose that the inverted Hebbian
      plasticity of synapses involved in local spikes, and/or local dendritic
      homeostatic plasticity, could prevent an unbalanced distribution of synaptic
      weights on the dendritic tree.

PMID- 12183195
TI  - Mechanisms of Pavlovian fear conditioning: has the engram been located?
AB  - Uncertainty persists as to whether the amygdala is a crucial site of plasticity
      for classically conditioned fear or merely a sensory relay to structures
      generating fear responses. A recent Nature study suggests that associative
      synaptic changes take place in neurons of the amygdala during fear conditioning,
      and that these changes require dopamine-mediated modulation. Nevertheless, these
      findings do not prove that the amygdala is a sufficient site of plasticity for
      fear memory.

PMID- 12183197
TI  - Raising the speed limit--fast Ca(2+) handling in dendritic spines.
AB  - Ca2+ influx into dendritic spines is involved in the induction of both long-term
      potentiation (LTP) and long-term depression (LTD) by activating distinct
      biochemical cascades, depending on the stimulation protocol. Such conditional
      activation can be explained by the finding that removal of Ca2+ from spines is
      extremely rapid (approximately 15 ms) and promoted by a low endogenous buffering
      capacity. As a consequence, the time course of influx and binding kinetics are
      important determinants of how much Ca2+ binds to a particular enzyme. In addition
      structural factors, such as shape and dendritic location, could contribute to
      fine-tuning of spine Ca2+ handling and synaptic modification.

PMID- 12183199
TI  - In vivo FM: using conventional fluorescence microscopy to monitor retinal
      neuronal death in vivo.
AB  - Post-traumatic death of mature retinal neurons occurs in glaucoma and after optic
      nerve injury. The death is a dynamic process that can be fully analyzed with
      methods that monitor changes over time. We have coupled the development of
      retrogradely transportable fluorescent dyes with modification of conventional
      epifluorescence microscopy to manipulate and visualize rat retinal neurons in
      vivo. The method is a relatively new concept and has potential for the monitoring
      of retinal conditions, such as glaucoma or optic nerve transection, and for
      evaluation of neuroprotective strategies in the near future.

PMID- 12183205
TI  - Modulation of synaptic delay during synaptic plasticity.
AB  - At most synapses, information about the processes underlying transmitter release
      evoked by a presynaptic action potential has been gathered indirectly, based on
      characterization of the postsynaptic response. Traditionally, the two
      electrophysiological parameters used for this indirect investigation are the
      amplitude and latency of the response. The amplitude measures amount of
      transmitter released; the latency (synaptic delay) reflects the kinetics of a
      sequence of events that culminates in release. The latency distribution of
      quantal events, or the time course of composite evoked responses, can be used to
      infer the time course of the elevated release probability following a stimulus.
      Recent studies have demonstrated that synaptic delay is not invariant, but is
      modifiable during several forms of short-term synaptic plasticity. This suggests
      that the step of transmitter secretion can be modulated directly. Several models
      for short-term synaptic plasticity are evaluated in the context of the observed
      changes in synaptic delay.

PMID- 12183206
TI  - Memory consolidation and the amygdala: a systems perspective.
AB  - The basolateral region of the amygdala (BLA) plays a crucial role in making
      significant experiences memorable. There is extensive evidence that stress
      hormones and other neuromodulatory systems activated by arousing training
      experiences converge in regulating noradrenaline-receptor activity within the
      BLA. Such activation of the BLA modulates memory consolidation via BLA
      projections to many brain regions involved in consolidating lasting memory,
      including the hippocampus, caudate nucleus, nucleus basalis and cortex.
      Investigation of the involvement of BLA projections to other brain regions is
      essential for understanding influences of the amygdala on different aspects and
      forms of memory.

PMID- 12183207
TI  - Do human bipeds use quadrupedal coordination?
AB  - Tackling the question of whether control of human gait is based on that of a
      quadrupedal locomotion system is of basic and practical relevance. During
      evolution, the increased influence of a direct cortical-motoneuronal system in
      parallel with more specialized hand function might have replaced phylogenetically
      older systems that organized locomotor movements. However, recent research
      indicates that interlimb coordination during human locomotion is organized in a
      similar way to that in the cat. Hence, it is hypothesized that during locomotion,
      corticospinal excitation of upper limb motoneurons is mediated indirectly, via
      propriospinal neurons in the cervical spinal cord. This allows a task-dependent
      neuronal linkage of cervical and thoraco-lumbar propriospinal circuits
      controlling leg and arm movements during human locomotor activities. The
      persistence of such movement control has consequences for rehabilitation and the
      applicability of animal research to human patients with spinal cord injury.

PMID- 12183208
TI  - Understanding pathogenesis and treatment of HIV dementia: a role for magnetic
      resonance?
AB  - HIV dementia (HIVD) is among the most common and most feared neurological
      complications of AIDS. In vitro studies have identified a constellation of
      potentially neurotoxic inflammatory and non-inflammatory pathways, one or more of
      which could underlie HIVD. Magnetic resonance spectroscopy (MRS) and magnetic
      resonance imaging (MRI) studies can distinguish between inflammatory and non
      inflammatory pathways in vivo and suggest that either or both might be active in
      different patients or at different times in the same patient. This could perhaps
      explain the variability in HIVD development, progression and response to therapy.
      These findings also suggest that MRI and MRS can identify patients at risk for
      HIVD and predict response to therapy.

PMID- 12183209
TI  - Cysteine regulation of protein function--as exemplified by NMDA-receptor
      modulation.
AB  - Until recently cysteine residues, especially those located extracellularly, were
      thought to be important for metal coordination, catalysis and protein structure
      by forming disulfide bonds - but they were not thought to regulate protein
      function. However, this is not the case. Crucial cysteine residues can be
      involved in modulation of protein activity and signaling events via other
      reactions of their thiol (sulfhydryl; -SH) groups. These reactions can take
      several forms, such as redox events (chemical reduction or oxidation), chelation
      of transition metals (chiefly Zn(2+), Mn(2+) and Cu(2+)) or S-nitrosylation [the
      catalyzed transfer of a nitric oxide (NO) group to a thiol group]. In several
      cases, these disparate reactions can compete with one another for the same thiol
      group on a single cysteine residue, forming a molecular switch composed of a
      latticework of possible redox, NO or Zn(2+) modifications to control protein
      function. Thiol-mediated regulation of protein function can also involve
      reactions of cysteine residues that affect ligand binding allosterically. This
      article reviews the basis for these molecular cysteine switches, drawing on the
      NMDA receptor as an exemplary protein, and proposes a molecular model for the
      action of S-nitrosylation based on recently derived crystal structures.

PMID- 12183210
TI  - Sesquicentenary of the birthday of Santiago Ramon y Cajal, the father of modern
      neuroscience.
AB  - The appearance of Santiago Ramon y Cajal in the world of neuroscience provoked a
      radical change in the course of its history. Cajal's studies of the microanatomy
      of virtually the whole CNS and his observations regarding degeneration and
      regeneration, together with his theories about the function, development and
      plasticity of the nervous system, had a profound impact on researchers of his
      era. These studies represent the roots of what are today some of the most
      exciting areas of discovery in terms of the structure and function of the brain
      in both sickness and health.

PMID- 12183213
TI  - Decreased inhibitory activity of PKC in OCD patients after six months of
      treatment.
AB  - We investigated 5-HT reuptake and protein kinase of type C (PKC) activation in
      platelets of 14 OCD patients at baseline and after six months of treatment with
      different serotonin (5-HT) reuptake inhibitors (SRIs). The results showed that
      all SRIs provoked a significant increase in both the maximal velocity (V(max))
      and the Michaelis-Menten constant (K(m)) of 5-HT reuptake, as compared with
      baseline values. The activation of PKC by means of 4-beta-12-tetradecanoylphorbol
      13-acetate provoked a significant decrease in V(max) values, but the effect was
      not as evident as at baseline. These findings could indicate that, in OCD
      patients, SRIs increase the rate of reuptake and decrease the inhibitory effect
      of PKC and that the two phenomena may be linked, the first perhaps depending upon
      the second.

PMID- 12183214
TI  - Salivary cortisol day profiles in elderly with mild cognitive impairment.
AB  - It is unknown whether hypothalamus-pituitary-adrenal (HPA) axis dysfunction is
      associated with the memory impairments observed among elderly participants with
      mild cognitive impairment (MCI), a group considered at increased risk for
      Alzheimer's disease (AD). Therefore, salivary cortisol levels were measured at
      six points over the course of the day while at-home in MCI participants (n=16),
      normal elderly (n=28), and young controls (n=14). Results revealed that MCI
      participants did not show elevated salivary cortisol levels. The 9 a.m. cortisol
      level of the MCI group was significantly lower than the 9 a.m. level of the young
      controls, but did not differ from those of the normal elderly group. In contrast
      to the other two groups, within the MCI group mean cortisol levels were inversely
      related to immediate recall of paragraphs. No association was observed between
      mean cortisol levels and performance in paired associates and digit span. Whether
      cortisol levels, in conjunction with other factors, such as hippocampal volume,
      will lead to improved prediction of future decline to AD in participants with MCI
      remains to be established in longitudinal studies.

PMID- 12183215
TI  - Potentiation of tumor metastasis in adulthood by neonatal endotoxin exposure: sex
      differences.
AB  - Previous research in rodents has demonstrated that neonatal exposure to bacterial
      endotoxin alters the hypothalamic-pituitary-adrenal (HPA) axis resulting in
      hypersecretion of corticosterone in response to stress in adulthood. Given the
      known interactions between glucocorticoids and the immune system we tested the
      hypothesis that such alterations may impact on immune outcomes. Male and female
      Fischer 344 neonate rats were treated with endotoxin (0.05 mg/kg
      lipopolysaccaride from Salmonella enteritidis) or vehicle on days 1, 3, 5 and 7
      postpartum. In adulthood, animals were subjected to chronic stress and the effect
      on resistance to tumor colonization (Exp. 1), natural killer (NK) cell activity
      (Exp. 2), and HPA reactivity (Exp. 3) was assessed. Neonatal endotoxin treatment
      was found to significantly impair NK cell activity and decrease resistance to
      tumor colonization in male but not female rats (P<0.05). Neonatal endotoxin
      exposure did not affect corticosterone responses to chronic stress in male or
      female rats, but the corticosterone response to acute stress was potentiated by
      endotoxin exposure, most notably in females. In conclusion, neonatal endotoxin
      exposure was found to be associated with a sexually differentiated impairment in
      tumor colonization and NK activity and long-term alterations in corticosterone
      responses to stress. The effect on tumor colonization and NK activity was not,
      however, critically mediated by corticosterone levels. These findings suggest
      that neonatal bacterial infections may have long-term health implications,
      specifically in terms of resistance to cancer spread in adulthood.

PMID- 12183216
TI  - Urinary cortisol and catecholamines in mothers of child cancer survivors with and
      without PTSD.
AB  - Reduced cortisol coupled with elevated catecholamines has been reported for
      patients with post-traumatic stress disorder (PTSD) precipitated by war and other
      traumas considered to be "outside the range of usual experiences". It is unclear
      whether these neuroendocrine abnormalities also occur in PTSD precipitated by
      more commonly experienced traumas associated with life-threatening illness.
      Overnight (12-h) urinary cortisol, norepinephrine (NE) and epinephrine (E) were
      measured in 21 mothers of pediatric cancer survivors with (n = 14) and without
      PTSD symptoms (n = 7) and in control mothers of healthy children (n = 8). Mothers
      meeting subthreshold and full PTSD criteria were combined to form the PTSD
      symptoms group. The PTSD group showed lower total urinary cortisol and a trend
      for higher total urinary NE than the non-PTSD group, who in turn were no
      different from controls. There were no significant group effects for E. Cortisol
      (but not NE) effects remained after controlling for symptoms of co-morbid
      depression. The finding of reduced cortisol in illness-related PTSD demonstrates
      neuroendocrine dysregulation similar to that found previously in other types of
      trauma (e.g., war-related). Future longitudinal studies with repeated urinary
      collection procedures will be necessary to clarify measurement issues and
      establish the time course and health implications of the neuroendocrine
      perturbations.

PMID- 12183217
TI  - Effect of diazepam on EEG power and coherent activity: sex differences.
AB  - Benzodiazepine-steroid interactions and sex differences in brain and circulating
      levels of gonadal steroids, lead to hypothesized differential effects of DZ on
      EEG in women and men. Coherent activity has been shown to be relevant for binding
      information into global percepts therefore diazepam effects on EEG correlation
      and sex differences were assessed in a double-blind crossover study. Healthy
      males (9) and females (9) received a single-dose (5 mg) of diazepam or placebo.
      EEG was recorded with eyes open (FP1, FP2, F3, F4, C3, C4, P3, P4, O1, O2) before
      and 2 h after drug administration in two counterbalanced sessions. DZ selectively
      increased delta and theta EEG correlation among frontal regions and decreased it
      between right parieto-occipital (theta) and fronto-central regions (alpha2) in
      addition to an increase in beta2 interhemispheric correlation in men and women.
      Men showed increased beta1 interhemispheric correlation, decreased alpha1 and
      increased beta power; women showed in addition, decreased theta and alpha2 power.
      theta rhythm was more sensitive to DZ in women, whereas interhemispheric
      correlation was more affected in men. DZ had a sexually dimorphic effect on
      waking EEG and a disrupting effect on coherent activity, increasing balance among
      frontal regions and decreasing temporal coupling between anterior-posterior
      regions. These sex differences might be related to differences in brain
      organization and activational effects of female gonadal steroids which are higher
      in women than in men.

PMID- 12183218
TI  - Verbal and spatial functions across the menstrual cycle in healthy young women.
AB  - The effects of the menstrual cycle on cognitive functions were investigated using
      simple verbal and spatial tasks. Eight healthy young women with a regular,
      established 28-day menstrual cycle and the occurrence of ovulation on day 14 were
      tested four times during one cycle. Ten women on non-tricyclic birth control
      pills were also tested weekly during one cycle. Both groups were matched in age,
      handedness and education. No significant difference in spatial ability was found
      but improved verbal working memory, as measured by the verbal span score, was
      associated with periods of high estrogen levels.

PMID- 12183219
TI  - Hypothalamic-pituitary-adrenal axis reactivity to psychological stress and memory
      in middle-aged women: high responders exhibit enhanced declarative memory
      performance.
AB  - According to recent studies, elevated cortisol levels are associated with
      impaired declarative memory performance. This specific effect of cortisol has
      been shown in several studies using pharmacological doses of cortisol. The
      present study was designed to determine the effects of endogenously stimulated
      cortisol secretion on memory performance in healthy middle-aged women. For
      psychological stress challenging, we employed the Trier Social Stress Test
      (TSST). Subjects were assigned to either the TSST or a non-stressful control
      condition. Declarative and non-declarative memory performance was measured by a
      combined priming-free-recall-task. No significant group differences were found
      for memory performance. Post hoc analyses of variance indicated that regardless
      of experimental condition the subjects with remarkably high cortisol increase in
      response to the experimental procedure (high responders) showed increased memory
      performance in the declarative task compared to subjects with low cortisol
      response (low responders). The results suggest that stress-induced cortisol
      failed to impair memory performance. The results are discussed with respect to
      gender-specific effects and modulatory effects of the sympathetic nervous system
      and psychological variables.

PMID- 12183220
TI  - Cortisol and behavior in fragile X syndrome.
AB  - OBJECTIVE: The purpose of this study was to determine if children with fragile X
      syndrome, who typically demonstrate a neurobehavioral phenotype that includes
      social anxiety, withdrawal, and hyper-arousal, have increased levels of cortisol,
      a hormone associated with stress. The relevance of adrenocortical activity to the
      fragile X phenotype also was examined. METHOD: One hundred and nine children with
      the fragile X full mutation (70 males and 39 females) and their unaffected
      siblings (51 males and 58 females) completed an in-home evaluation including a
      cognitive assessment and a structured social challenge task. Multiple samples of
      salivary cortisol were collected throughout the evaluation day and on two typical
      non-school days. Measures of the fragile X mental retardation (FMR1) gene, child
      intelligence, the quality of the home environment, parental psychopathology, and
      the effectiveness of educational and therapeutic services also were collected.
      Linear mixed-effects analyses were used to examine differences in cortisol
      associated with the fragile X diagnosis and gender (fixed effects) and to
      estimate individual subject and familial variation (random effects) in cortisol
      hormone levels. Hierarchical multiple regression analyses were conducted to
      determine whether adrenocortical activity is associated with behavior problems
      after controlling for significant genetic and environmental factors. RESULTS:
      Results showed that children with fragile X, especially males, had higher levels
      of salivary cortisol on typical days and during the evaluation. Highly
      significant family effects on salivary cortisol were detected, consistent with
      previous work documenting genetic and environmental influences on adrenocortical
      activity. Increased cortisol was significantly associated with behavior problems
      in boys and girls with fragile X but not in their unaffected siblings.
      CONCLUSIONS: These results provide evidence that the function of the hypothalamic
      pituitary-adrenal axis may have an independent association with behavioral
      problems in children with fragile X syndrome.

PMID- 12183221
TI  - Neuroendocrine evaluation of 5-HT1A function in male alcoholic patients.
AB  - BACKGROUND: Preclinical evidences support the hypothesis of a serotonergic
      dysfunction in alcohol preference. In human, studies have demonstrated a
      serotonergic hypoactivity in alcoholism. However, little is known about the role
      of 5-HT1A receptors. METHODS: We assessed the hormonal (prolactin and cortisol)
      responses to flesinoxan (a highly potent and selective 5-HT1A agonist) in 12 male
      inpatients meeting DSM-IV criteria for alcohol dependence, 3 weeks after the last
      reported use of alcohol and antidepressants. These patients were compared to 10
      male controls. RESULTS: There was a highly significant difference between
      alcoholic patients and controls for the area under the curve relative (AUCr)
      values of prolactin responses. AUCr values of cortisol responses to flesinoxan
      showed a trend towards lower values in alcoholics compared to controls.
      CONCLUSION: These results support the implication of the serotonergic system, and
      particularly a decreased sensitivity of post-synaptic 5-HT1A receptors, in
      alcoholism.

PMID- 12183222
TI  - Resistance to macrolides and related antibiotics in Streptococcus pneumoniae.

PMID- 12183224
TI  - Evaluation of antibiotic susceptibilities of three rickettsial species including
      Rickettsia felis by a quantitative PCR DNA assay.
AB  - Rickettsiae grow only intracellularly, and the antibiotic susceptibilities of
      these bacteria have been assessed by either plaque, dye uptake, or
      immunofluorescence assays, which are time-consuming. We used a quantitative PCR
      (with the LightCycler instrument) to assess the levels of inhibition of
      Rickettisa felis, R. conorii, and R. typhi DNA synthesis in the presence of
      various antibiotics. We established the kinetics of rickettsial DNA during growth
      and showed that R. conorii grows more quickly than R. typhi in cell culture, with
      maximum replication occurring after 5 and 7 days, respectively. The MICs of the
      antibiotics tested for R. conorii and R. typhi by the quantitative PCR assay were
      similar to those previously obtained by plaque and dye uptake assays. We found
      that R. felis is susceptible to doxycycline, rifampin, thiamphenicol, and
      fluoroquinolones but not to gentamicin, erythromycin, amoxicillin, or
      trimethoprim-sulfamethoxazole. The resistance of this new species to erythromycin
      is consistent with its current taxonomic position within the spotted fever group.
      We believe that quantitative PCR could be used in the future to simplify and
      shorten antibiotic susceptibility assays of other rickettsiae and other strict
      intracellular pathogens.

PMID- 12183223
TI  - Importance of the fourth alpha-helix within the CAP homology domain of type II
      topoisomerase for DNA cleavage site recognition and quinolone action.
AB  - We report that point mutations causing alteration of the fourth alpha-helix
      (alpha4-helix) of the CAP homology domain of eukaryotic (Saccharomyces
      cerevisiae) type II topoisomerases (Ser(740)Trp, Gln(743)Pro, and Thr(744)Pro)
      change the selection of type II topoisomerase-mediated DNA cleavage sites
      promoted by Ca(2+) or produced by etoposide, the fluoroquinolone CP-115,953, or
      mitoxantrone. By contrast, Thr(744)Ala substitution had minimal effect on Ca(2+)-
      and drug-stimulated DNA cleavage sites, indicating the selectivity of single
      amino acid substitutions within the alpha4-helix on type II topoisomerase
      mediated DNA cleavage. The equivalent mutation in the gene for Escherichia coli
      gyrase causing Ser(83)Trp also changed the DNA cleavage pattern generated by
      Ca(2+) or quinolones. Finally, Thr(744)Pro substitution in the yeast type II
      topoisomerase rendered the enzyme sensitive to antibacterial quinolones. This
      study shows that the alpha4-helix within the conserved CAP homology domain of
      type II topoisomerases is critical for selecting the sites of DNA cleavage. It
      also demonstrates that selective amino acid residues in the alpha4-helix are
      important in determining the activity and possibly the binding of quinolones to
      the topoisomerase II-DNA complexes.

PMID- 12183225
TI  - N-alkyl urea hydroxamic acids as a new class of peptide deformylase inhibitors
      with antibacterial activity.
AB  - Peptide deformylase (PDF) is a prokaryotic metalloenzyme that is essential for
      bacterial growth and is a new target for the development of antibacterial agents.
      All previously reported PDF inhibitors with sufficient antibacterial activity
      share the structural feature of a 2-substituted alkanoyl at the P(1)' site. Using
      a combination of iterative parallel synthesis and traditional medicinal
      chemistry, we have identified a new class of PDF inhibitors with N-alkyl urea at
      the P(1)' site. Compounds with MICs of <or=4 micro g/ml against gram-positive and
      gram-negative pathogens, including Staphylococcus aureus, Streptococcus
      pneumoniae, and Haemophilus influenzae, have been identified. The concentrations
      needed to inhibit 50% of enzyme activity (IC(50)s) for Escherichia coli Ni-PDF
      were <or=0.1 micro M, demonstrating the specificity of the inhibitors. In
      addition, these compounds were very selective for PDF, with IC(50)s of
      consistently >200 micro M for matrilysin and other mammalian metalloproteases.
      Structure-activity relationship analysis identified preferred substitutions
      resulting in improved potency and decreased cytotoxity. One of the compounds
      (VRC4307) was cocrystallized with PDF, and the enzyme-inhibitor structure was
      determined at a resolution of 1.7 A. This structural information indicated that
      the urea compounds adopt a binding position similar to that previously determined
      for succinate hydroxamates. Two compounds, VRC4232 and VRC4307, displayed in vivo
      efficacy in a mouse protection assay, with 50% protective doses of 30.8 and 17.9
      mg/kg of body weight, respectively. These N-alkyl urea hydroxamic acids provide a
      starting point for identifying new PDF inhibitors that can serve as antimicrobial
      agents.

PMID- 12183226
TI  - Oxidative stress increases susceptibility of Mycobacterium tuberculosis to
      isoniazid.
AB  - Isoniazid is a first-line antibiotic used in the treatment of infections caused
      by Mycobacterium tuberculosis. Isoniazid is a prodrug requiring oxidative
      activation by the catalase-peroxidase hemoprotein, KatG. Resistance to isoniazid
      can be obtained by point mutations in the katG gene, with one of the most common
      being a threonine-for-serine substitution at position 315 (S315T). The S315T
      mutation is found in more than 50% of isoniazid-resistant clinical isolates and
      results in an approximately 200-fold increase in the MIC of isoniazid compared to
      that for M. tuberculosis H37Rv. In the present study we investigated the
      hypothesis that superoxide plays a role in KatG-mediated isoniazid activation.
      Plumbagin and clofazimine, compounds capable of generating superoxide anion,
      resulted in a lower MIC of isoniazid for M. tuberculosis H37Rv and a strain
      carrying the S315T mutation. These agents did not cause as great of an increase
      in isoniazid susceptibility in the mutant strain when the susceptibilities were
      assessed by using the inhibitory concentration that causes a 50% decrease in
      growth. These results provide evidence that superoxide can play a role in
      isoniazid activation. Since clofazimine alone has antitubercular activity, the
      observation of synergism between clofazimine and isoniazid raises the interesting
      possibility of using both drugs in combination to treat M. tuberculosis
      infections.

PMID- 12183227
TI  - Heterologous expression of epothilone biosynthetic genes in Myxococcus xanthus.
AB  - Epothilones are potential anticancer drugs that stabilize microtubules in a
      manner similar to paclitaxel (Taxol). Epothilones are produced from the
      myxobacterium Sorangium cellulosum, which has a 16-h doubling time and produces
      only milligram-per-liter amounts of epothilone A and epothilone B. Furthermore,
      genetic manipulation of S. cellulosum is difficult. To produce epothilones in a
      more genetically amenable and rapidly growing host, we chose the closely related
      and best-characterized myxobacteria Myxococcus xanthus. We inserted 65.4 kb of S.
      cellulosum DNA that encompassed the entire epothilone gene cluster into the
      chromosome of M. xanthus by a series of homologous recombination events. The
      resulting strain produced epothilones A and B. Construction of a strain that
      contained a mutation in epoK, the P450 epoxidase, resulted in production of
      epothilones C and D.

PMID- 12183228
TI  - Different levels of genetic homogeneity in vancomycin-resistant and -susceptible
      Enterococcus faecium isolates from different human and animal sources analyzed by
      amplified-fragment length polymorphism.
AB  - The genetic relationship among fecal vancomycin-resistant Enterococcus faecium
      (VREF) and vancomycin-susceptible E. faecium (VSEF) isolates (n = 178) from the
      same populations of pigs, human healthy volunteers, and hospitalized patients
      (from The Netherlands) and chickens (from The Netherlands and Greece) was studied
      by amplified-fragment length polymorphism (AFLP). The majority of VREF isolates
      from pigs, healthy volunteers, and hospitalized patients grouped together
      (genetic similarity, >or=65%). In a previous AFLP study by our group the VREF
      isolates from hospitalized patients grouped separately, most likely because these
      were clinical and not fecal isolates as in the present study. Furthermore, VSEF
      isolates from humans and pigs were found much more genetically diverse than VREF
      isolates, whereas VREF and VSEF isolates from chickens clustered together in a
      separate genogroup (genetic similarity, >or=65%), a pattern clearly distinct from
      the patterns for human and pig isolates. The present study suggests that pigs are
      a more important source of VREF for humans than chickens and that human- and pig
      derived VSEF isolates seem much more heterogeneous than VREF isolates.

PMID- 12183229
TI  - The LisRK signal transduction system determines the sensitivity of Listeria
      monocytogenes to nisin and cephalosporins.
AB  - The Listeria monocytogenes two-component signal transduction system, LisRK,
      initially identified in strain LO28, plays a significant role in the virulence
      potential of this important food-borne pathogen. Here, it is shown that, in
      addition to its major contribution in responding to ethanol, pH, and hydrogen
      peroxide stresses, LisRK is involved in the ability of the cell to tolerate
      important antimicrobials used in food and in medicine, e.g., the lantibiotic
      nisin and the cephalosporin family of antibiotics. A (Delta)lisK mutant (lacking
      the LisK histidine kinase sensor component) displays significantly enhanced
      resistance to the lantibiotic nisin, a greatly enhanced sensitivity to the
      cephalosporins, and a large reduction in the expression of three genes thought to
      encode a penicillin-binding protein, another histidine kinase (other than LisK),
      and a protein of unknown function. Confirmation of the role of LisRK was obtained
      when the response regulator, LisR, was overexpressed using both constitutive and
      inducible (nisin-controlled expression) systems. Under these conditions we
      observed a reversion of the (Delta)lisK mutant to wild-type growth kinetics in
      the presence of nisin. It was also found that overexpression of LisR complemented
      the reduced expression of two of the aforementioned genes. These results
      demonstrate the important role of LisRK in the response of L. monocytogenes to a
      number of antimicrobial agents.

PMID- 12183230
TI  - Genetic and biochemical characterization of CGB-1, an Ambler class B carbapenem
      hydrolyzing beta-lactamase from Chryseobacterium gleum.
AB  - Chryseobacterium gleum (previously included in the Flavobacterium IIb species) is
      a gram-negative aerobe that is a source of nosocomial infections. An Ambler class
      B beta-lactamase gene was cloned and expressed in Escherichia coli from reference
      strain C. gleum CIP 103039 that had reduced susceptibility to expanded-spectrum
      cephalosporins and carbapenems. The purified beta-lactamase, CGB-1, with a pI
      value of 8.6 and a determined relative molecular mass of ca. 26 kDa, hydrolyzed
      penicillins; narrow- and expanded-spectrum cephalosporins; and carbapenems. CGB-1
      was a novel member of the molecular subclass B1 of metallo-enzymes. It had 83 and
      42% amino acid identity with IND-1 from Chryseobacterium indologenes and BlaB
      from C. meningosepticum, respectively. Thus, in addition to the previously
      characterized clavulanic acid-inhibited extended-spectrum beta-lactamase CGA-1 of
      Ambler class A, C. gleum produces a very likely chromosome-borne class B beta
      lactamase.

PMID- 12183231
TI  - Frequency of disinfectant resistance genes and genetic linkage with beta
      lactamase transposon Tn552 among clinical staphylococci.
AB  - A total of 61 strains of Staphylococcus aureus and 177 coagulase-negative
      staphylococcal strains were isolated from the blood of patients with bloodstream
      infections and from the skin of both children under cancer treatment and human
      immunodeficiency virus-positive patients. The MIC analyses revealed that 118
      isolates (50%) were resistant to quaternary ammonium compound-based disinfectant
      benzalkonium chloride (BC). The frequencies of resistance to a range of
      antibiotics were significantly higher among BC-resistant staphylococci than among
      BC-sensitive staphylococci. Of 78 BC-resistant staphylococcal isolates, plasmid
      DNA from 65 (83%), 2 (3%), 43 (55%), and 15 (19%) isolates hybridized to qacA or 
      B (qacA/B), qacC, blaZ, and tetK probes, respectively. The qacA/B and blaZ probes
      hybridized to the same plasmid in 19 (24%) staphylococcal strains. The plasmids
      harboring both qacA/B and blaZ genes varied from approximately 20 to 40 kb. The
      Staphylococcus epidermidis Fol62 isolate, harboring multiresistance plasmid
      pMS62, contained qacA/B and blaZ together with tetK. Molecular and genetic
      studies indicated different structural arrangements of blaZ and qacA/B, including
      variable intergenic distances and transcriptional directions of the two genes on
      the same plasmid within the strains. The different organizations may be due to
      the presence of various genetic elements involved in cointegration,
      recombination, and rearrangements. These results indicate that qac resistance
      genes are common and that linkage between resistance to disinfectants and
      penicillin resistance occurs frequently in clinical isolates in Norway. Moreover,
      the higher frequency of antibiotic resistance among BC-resistant strains
      indicates that the presence of either resistance determinant selects for the
      other during antimicrobial therapy and disinfection in hospitals.

PMID- 12183232
TI  - Isoniazid-induced transient high-level resistance in Mycobacterium tuberculosis.
AB  - An American Type Culture Collection reference strain and eight clinical strains
      of Mycobacterium tuberculosis, all of which were susceptible to isoniazid (INH)
      (mean MIC, 0.06 mg/liter) and negative for the Ser315Thr katG mutation, were left
      in their BACTEC 12B vials (for use with the BACTEC 460-TB method) containing 0.1
      mg of INH per liter for periods of up to 28 days after the completion of the
      antibiotic susceptibility test. Each eventually grew to levels compatible with
      those of INH-resistant strains. Successive passages in INH-containing BACTEC 12B
      vials and onto solid media showed that the resistance noted above was maintained.
      Successive passages of these M. tuberculosis strains in which INH resistance had
      been induced into BACTEC 12B vials or solid media containing stepwise increases
      in INH concentrations eventually yielded organisms resistant to 20 mg of INH per
      liter. Transfer of cells in which INH resistance had been induced to drug-free
      medium followed by repeated passages in that medium eventually yielded organisms
      whose susceptibility to INH was identical to that of the original parent strains.
      The cycle of induced INH resistance could be repeated with these now INH
      susceptible cells. The use of M. tuberculosis identification probes and IS6110
      based restriction fragment length polymorphism analyses of cultures throughout
      the induction of INH resistance and the reversal of resistance in drug-free
      medium eliminated the possibility that the culture was contaminated or that the
      initial specimen had a mixed type of infection. Induced high-level resistance to
      INH (20 mg/liter) could be reduced 100-fold with a subinhibitory concentration of
      reserpine but not with verapamil. These results collectively suggest that high
      level resistance to INH can be induced in INH-susceptible M. tuberculosis strains
      by the induction of a reserpine-sensitive efflux mechanism.

PMID- 12183233
TI  - Identification and analysis of amino acid mutations in porin IB that mediate
      intermediate-level resistance to penicillin and tetracycline in Neisseria
      gonorrhoeae.
AB  - PenB is the third resistance determinant in the stepwise acquisition of multiple
      resistance genes in chromosomally mediated resistant Neisseria gonorrhoeae
      (CMRNG). Alterations in por(IB), one of two alleles at the por locus that encodes
      the outer membrane protein porin IB (PIB), were recently reported to be
      responsible for the increased resistance to penicillin and tetracycline conferred
      by penB, but the specific mutations conferring antibiotic resistance were not
      identified experimentally. To determine which amino acids in PIB confer increased
      resistance, we transformed a recipient strain with chimeras of the por(IB) genes
      from strains FA1090 and FA140 (penB2). These studies revealed that two amino acid
      changes, G120D and A121D, were both necessary and sufficient to confer increased
      resistance to penicillin and tetracycline. Site-saturation and site-directed
      mutagenesis of Gly-120 and Ala-121 revealed that both a single mutation, G120K,
      and the double mutations G120R A121H and G120P A121P also conferred antibiotic
      resistance to the recipient strain. The identical mutations in PIA increased
      penicillin and tetracycline resistance either moderately or not at all. Analysis
      of por(IB) genes present in the GenBank database from 51 clinical isolates
      demonstrated that lysine and aspartate mutations at positions 120 and/or 121 also
      occur in nature. These studies demonstrate that charged amino acids at positions
      120 and 121 in PIB are highly preferential for conferring resistance to
      penicillin and tetracycline in N. gonorrhoeae.

PMID- 12183234
TI  - Antibiotic resistance genes and Salmonella genomic island 1 in Salmonella
      enterica serovar Typhimurium isolated in Italy.
AB  - Fifty-four epidemiologically unrelated multidrug-resistant Salmonella enterica
      serovar Typhimurium isolates, collected between 1992 and 2000 in Italy, were
      analyzed for the presence of integrons. Strains were also tested for Salmonella
      genomic island 1 (SGI1), carrying antibiotic resistance genes in DT104 strains. A
      complete SGI1 was found in the majority of the DT104 strains. Two DT104 strains,
      showing resistance to streptomycin-spectinomycin and sulfonamides, carried a
      partially deleted SGI1 lacking the flo(st), tetR, and tetA genes, conferring
      chloramphenicol-florfenicol and tetracycline resistance, and the integron
      harboring the pse-1 gene cassette, conferring ampicillin resistance. The presence
      of SGI1 was also observed in serovar Typhimurium strains belonging to other phage
      types, suggesting either the potential mobility of this genomic island or changes
      in the phage-related phenotype of DT104 strains.

PMID- 12183235
TI  - The Candida dubliniensis CdCDR1 gene is not essential for fluconazole resistance.
AB  - The present study investigated the role of the Candida dubliniensis CdCDR1 and
      CdCDR2 genes in the development of fluconazole resistance. The C. dubliniensis
      CdCDR1 gene was 92% identical at the nucleotide sequence level to the
      corresponding C. albicans gene. However, 58% (14 of 24) of C. dubliniensis
      genotype 1 isolates tested harbored a nonsense mutation in the CdCDR1 open
      reading frame that converted codon 756 (TAT) to a TAG translational stop codon.
      Analysis of five of these C. dubliniensis isolates by Western immunoblotting
      showed that they expressed a truncated 85-kDa CdCdr1p compared to the full-length
      170-kDa CdCdr1p. Expression of CdCDR1 alleles from six C. dubliniensis isolates
      in a pdr5 Saccharomyces cerevisiae strain revealed that CdCDR1 alleles from three
      isolates that encoded truncated proteins were unable to confer resistance to
      drugs and antifungals. However, reassignment of the TAG sequence at codon 756 to
      TAT (encoding tyrosine) in an allele from strain CD36 conferred the ability to
      mediate resistance to multiple drugs. Fluconazole-resistant isolates of C.
      dubliniensis harboring functional alleles of CdCDR1 were found to exhibit two- to
      ninefold-higher levels of CdCDR1 mRNA than did matched fluconazole-susceptible
      isolates. By comparison, levels of CdMDR1 expression ranged from approximately 50
      to 100-fold greater in resistant isolates. Fluconazole resistance was also
      identified in isolates harboring nonfunctional CdCDR1 alleles, but resistance in
      these isolates was only associated with increased CdMDR1 expression. Targeted
      disruption of two functional alleles of CdCDR1 in a fluconazole-resistant
      derivative of C. dubliniensis that overexpressed both CdCDR1 and CdMDR1 revealed
      that although CdCDR1 was important for mediating reduced susceptibility to
      itraconazole and ketoconazole, there was no affect on fluconazole susceptibility
      in the double mutant. Evidence presented in this study reveals that CdCDR1 is not
      essential for the development of fluconazole resistance in C. dubliniensis.

PMID- 12183236
TI  - Effect of 5-iodo-2'-deoxyuridine on vaccinia virus (orthopoxvirus) infections in
      mice.
AB  - There is a concern that there may be unregistered stocks of smallpox that can be
      used for bioterrorism or biological warfare. According to the WHO Advisory
      Committee on Variola Research, there is a need to develop strategies to treat
      smallpox infections should they reappear. It would also be important to have an
      effective drug at hand for the treatment of monkeypox disease in humans. We show
      here that 5-iodo-2'-deoxyuridine (IDU) is a potent inhibitor of vaccinia virus
      (VV) replication and that IDU inhibits VV DNA synthesis in a dose-dependent way.
      The in vivo protective effect of IDU was assessed in the VV tail lesion model in
      immunocompetent mice and in a lethal model for VV infection in SCID (severe
      combined immune deficiency) mice that had been infected either intranasally,
      intraperitoneally, or intravenously. Subcutaneous treatment with IDU at 150 and
      100 mg/kg of body weight markedly reduced the number of tail lesions in
      immunocompetent NMRI mice. Untreated intranasally VV-infected SCID mice died at
      20.8 +/- 3.1 days after infection (mean +/- standard deviation). Treatment with
      IDU (subcutaneously, 150 mg/kg/day [from day 0 to 4] and 75 mg/kg/day [from day 6
      to 11]) delayed-virus induced mortality by 15 days (mean day of death +/-
      standard deviation, 35.8 +/- 6.7; P < 0.0001). This protective effect was
      associated with (i) an improvement of lung histology and (ii) a marked reduction
      in lung viral titers. IDU also delayed VV-induced mortality when mice had either
      been infected intraperitoneally or intravenously. Even when the start of
      treatment with IDU (in intraperitoneally VV-infected mice) was postponed until 2
      or 4 days after infection, an important delay in virus-induced mortality was
      noted.

PMID- 12183237
TI  - Penciclovir susceptibilities of herpes simplex virus isolates from patients using
      penciclovir cream for treatment of recurrent herpes labialis.
AB  - The antiherpesvirus agent penciclovir (PCV) shares an identical activation
      pathway and a similar mode of action with acyclovir (ACV). However, since PCV
      represents a relatively recent treatment option, the clinical resistance profile
      to PCV is less well known. A susceptibility program was established to assess the
      resistance profile for serial herpes simplex virus isolates from immunocompetent
      patients with recurrent herpes labialis obtained throughout a 4-day period of
      treatment with topical PCV (1% cream) or a placebo. Two isolates (2 of 1,035
      [0.19%]), representing 0.34% of the patients (2 of 585), were confirmed to be PCV
      resistant (Pcv(r)) herpes simplex virus type 1 by a plaque reduction assay in MRC
      5 cells. These two viruses were highly resistant to PCV (50% inhibitory
      concentrations [IC(50)s], >55 micro g/ml) and were isolated less than 17 h after
      the start of patient-initiated treatment. However, subsequent isolates on days 2
      and 3 from these patients were completely susceptible to PCV (IC(50)s, <2.0 micro
      g/ml). Thus, it is not clear whether the resistance to PCV for these two early
      treatment isolates was directly associated with the 17 h of PCV treatment;
      several possible explanations are discussed. In an analysis of the distribution
      of IC(50) differences between the first and last isolates, there were three
      patients with minor IC(50) increases in the PCV-treated population and one in the
      placebo-treated group, although statistically, only the latter was an outlier. No
      patients were found to have Pcv(r) virus at the end of acute treatment,
      regardless of treatment group. Overall, the prevalence of Pcv(r) was found to be
      similar to the 0.3% Acv(r) reported for immunocompetent, untreated populations.

PMID- 12183238
TI  - Samarangenin B from Limonium sinense suppresses herpes simplex virus type 1
      replication in Vero cells by regulation of viral macromolecular synthesis.
AB  - Inhibitory effects of ethanolic extracts from 10 Chinese herbs on herpes simplex
      virus type 1 (HSV-1) replication were investigated. By a bioassay-guided
      fractionation procedure, samarangenin B (Sam B) was isolated from Limonium
      sinense; Sam B significantly suppressed HSV-1 multiplication in Vero cells
      without apparent cytotoxicity. Time-of-addition experiments suggested that the
      inhibitory action of Sam B on HSV-1 replication was not due to the blocking of
      virus adsorption. In an attempt to further localize the point in the HSV-1
      replication cycle where arrest occurred, a set of key regulatory events leading
      to viral multiplication was examined, including viral immediate-early (alpha),
      early (beta), and late (gamma) gene expression and DNA replication. Results
      indicated that levels of glycoprotein B (gB), gC, gD, gG, and infected-cell
      protein 5 (ICP5) expression and gB mRNA expression in Vero cells were impeded by
      Sam B. Data from PCR showed that replication of HSV-1 DNA in Vero cells was
      arrested by Sam B. Furthermore, Sam B decreased DNA polymerase, ICP0, and ICP4
      gene expression in Vero cells. Results of an electrophoretic mobility shift assay
      demonstrated that Sam B interrupted the formation of an alpha-trans-induction
      factor/C1/Oct-1/GARAT multiprotein complex. The mechanisms of antiviral action of
      Sam B seem to be mediated, at least in part, by inhibiting HSV-1 alpha gene
      expression, including expression of the ICP0 and ICP4 genes, by blocking beta
      transcripts such as DNA polymerase mRNA, and by arresting HSV-1 DNA synthesis and
      structural protein expression in Vero cells. These results show that Sam B is an
      antiviral agent against HSV-1 replication.

PMID- 12183239
TI  - Immunomodulatory effect of zidovudine (ZDV) on cytotoxic T lymphocytes previously
      exposed to ZDV.
AB  - In a previous study, zidovudine (ZDV) was shown to cause a concentration
      dependent inhibition of antigen-specific cytotoxic T-lymphocyte (CTL) clonal
      expansion (S. Francke, C. G. Orosz, K. A. Hayes, and L. E. Mathes, Antimicrob.
      Agents Chemother. 44:1900-1905, 2000). However, this suppressive effect was lost
      if exposure to ZDV was delayed for 24 to 48 h during the antigen sensitization
      period, suggesting that antigen-primed CTL may be less susceptible than naive T
      lymphocytes to the suppressive effects of ZDV. The present study was undertaken
      to determine if naive T lymphocytes were more sensitive to the suppressive
      effects of ZDV than T lymphocytes previously exposed to antigen. The 50%
      inhibitory concentration (IC(50)) values of ZDV were determined on naive and
      antigen-primed T-cell responses in an alloantigen system. Lymphocyte cultures
      with continuous antigen exposure (double prime) were more resistant to ZDV
      suppression (IC(50) = 316 micro M) than were naive lymphocytes (IC(50) = 87.5
      micro M). Interestingly, lymphocytes that were antigen primed but deprived of
      antigen during the final 7 days of culture (prime/hold) were exquisitely
      sensitive to ZDV suppression (IC(50) = 29.3 micro M). The addition of 80 micro M
      ZDV during the initial priming of the single-prime (prime/hold) and double-prime
      cultures did not select for a more drug-resistant cell population. The
      differences in ZDV sensitivities are likely a reflection of the physiological
      properties of the lymphocytes related to their activation state.

PMID- 12183240
TI  - Antiviral activities of MCC-478, a novel and specific inhibitor of hepatitis B
      virus.
AB  - MCC-478 is a newly synthesized 2-amino-6-arylthio-9-phosphonomethoxyethylpurine
      bis(2,2,2-trifluoroethyl) ester derivative. MCC-478 showed a substantially higher
      (ca. 80-fold) anti-hepatitis B virus (HBV) activity than that of lamivudine,
      despite no significant anti-human immunodeficiency virus activity. Since the
      bis(2,2,2-trifluoroethyl) ester group was used to improve the oral
      bioavailability of the phosphonomethoxyethylpurine derivatives, two monoester
      derivatives and one phosphonic acid derivative were also evaluated. It was
      suggested that these hydrolyzed derivatives, which appeared in animals given MCC
      478, have enough anti-HBV activity to contribute to efficacy in vivo.
      Furthermore, no apparent cytotoxic effects or reductions of mitochondrial DNA
      content by MCC-478 and its derivatives were observed. These results indicated
      that MCC-478 may be a new promising anti-HBV agent.

PMID- 12183241
TI  - Effects of neutrophils on cefazolin activity and penicillin-binding proteins in
      Staphylococcus aureus abscesses.
AB  - Bacteria survive within abscesses despite antimicrobial therapy, usually
      necessitating drainage. Our previous work showed that bacterial killing is
      diminished within the neutrophils of animals with abscesses. To further assess
      the role of neutrophils in Staphylococcus aureus survival and the poor activities
      of beta-lactams in abscesses, tissue cage abscess-bearing rats were given
      polymorphonuclear leukocyte (PMN)-depleting antibody prior to and several times
      following inoculation of the tissue cages with S. aureus. Cefazolin (300 mg/kg of
      body weight/day) was administered to all animals in appropriately divided doses.
      After 7 days of antimicrobial therapy, the 17 animals that received anti-PMN
      serum had significantly fewer abscess neutrophils than the 18 controls and fewer
      abscess bacteria (5.55 versus 3.79 log(10) CFU/ml [P = 0.04]) than the 18
      controls. The data were consistent with the premise that cefazolin is more
      effective in abscesses depleted of neutrophils. To investigate further, S. aureus
      was incubated with rat peritoneal neutrophils; and bacterial cell membrane
      proteins were isolated, labeled with biotinylated ampicillin, separated by
      electrophoresis, blotted onto nitrocellulose, and stained for biotin reactivity.
      PBP 2 expression was consistently and significantly decreased after a brief,
      nonkilling PMN exposure. These experiments showed that PMN depletion enhanced the
      activity of cefazolin in the abscess milieu. Furthermore, altered bacterial cell
      wall cefazolin targets may be the mechanism by which the PMN diminishes
      antimicrobial activity, suggesting the importance of the staphylococcus-PMN
      interaction in the outcome of established infections.

PMID- 12183242
TI  - Efficacy of quinupristin-dalfopristin in preventing vascular graft infection due
      to Staphylococcus epidermidis with intermediate resistance to glycopeptides.
AB  - A rat model was used to investigate the efficacy of quinupristin-dalfopristin (Q
      D) in the prevention of vascular prosthetic graft infection due to methicillin
      resistant Staphylococcus epidermidis with intermediate resistance to
      glycopeptides. The in vitro activity of the compound was compared to that of
      vancomycin by MIC determination and time-kill study. Moreover, the efficacy of
      collagen-sealed Q-D-soaked Dacron was evaluated in a rat model of graft
      infection. Graft infections were established in the subcutaneous tissue of the
      backs of 120 adult male Wistar rats. The in vivo study included a control group,
      one contaminated group that did not receive any antibiotic prophylaxis, two
      contaminated groups that received grafts soaked with 10 and 100 micro g of Q-D
      per ml, respectively, and two contaminated groups that received grafts soaked
      with 10 and 100 micro g of vancomycin per ml, respectively. Rats that received
      Dacron grafts soaked with 100 micro g of Q-D per ml showed no evidence of
      infection (<10 CFU/ml). In contrast, for rats that received Dacron grafts soaked
      with 10 micro g of Q-D per ml and Dacron grafts soaked with 10 or 100 micro g of
      vancomycin per ml, the quantitative graft cultures demonstrated 2.2 x 10(2) +/-
      1.3 x 10(2), 2.2 x 10(6) +/- 1.9 x 10(5), and 5.6 x 10(2) +/- 0.3 x 10(2) CFU/ml,
      respectively. Taken together the results of the study demonstrate that the use of
      Dacron grafts soaked with Q-D can result in significant bacterial growth
      inhibition and show that this compound is potentially valuable for prevention of
      vascular prosthetic graft infection.

PMID- 12183243
TI  - In vitro and in vivo synergy of fosmidomycin, a novel antimalarial drug, with
      clindamycin.
AB  - Fosmidomycin acts through inhibition of 1-deoxy-D-xylulose 5-phosphate (DOXP)
      reductoisomerase, a key enzyme of the nonmevalonate pathway of isoprenoid
      biosynthesis. It possesses potent antimalarial activity in vitro and in murine
      malaria. In a recent clinical study, fosmidomycin was effective and well
      tolerated in the treatment of patients with acute uncomplicated Plasmodium
      falciparum malaria but resulted in an unacceptably high rate of recrudescence. In
      order to identify a potential combination partner, the interaction of
      fosmidomycin with a number of antimalarial drugs in current use was investigated
      in a series of in vitro experiments. Synergy was observed between fosmidomycin
      and the lincosamides, lincomycin and clindamycin. The efficacy of a combination
      of fosmidomycin and clindamycin was subsequently demonstrated in the Plasmodium
      vinckei mouse model.

PMID- 12183244
TI  - Ertapenem versus ceftriaxone followed by appropriate oral therapy for treatment
      of complicated urinary tract infections in adults: results of a prospective,
      randomized, double-blind multicenter study.
AB  - The efficacy and safety of intravenous (i.v.) ertapenem (1 g once a day) with the
      option to switch to an oral agent for treatment of adults with complicated
      urinary tract infections (UTIs) were compared with that of i.v. ceftriaxone (1 g
      daily) with the same oral switch option in a multicenter, double-blind,
      prospective, randomized study. At entry, 592 patients were assigned to one of two
      strata: acute pyelonephritis or other complicated UTI without acute
      pyelonephritis. After a minimum of 3 days, patients could be switched to an oral
      antimicrobial agent. A total of 159 patients in the ertapenem group and 171
      patients in the ceftriaxone group were microbiologically evaluable. Approximately
      95% of patients in each treatment group were switched to oral therapy. The most
      common pathogens were Escherichia coli and Klebsiella pneumoniae. At the primary
      efficacy endpoint 5 to 9 days after treatment, 91.8% of patients who received
      ertapenem and 93.0% of those who received ceftriaxone had a favorable
      microbiological response (95% confidence interval for the difference, adjusting
      for strata, -7.6 to 5.1%), indicating that outcomes in the two treatment groups
      were equivalent. Microbiological success rates for the two treatment groups were
      similar when compared by stratum and also by severity of infection. The frequency
      and severity of drug-related adverse events were generally similar in both
      treatment groups. In this study, ertapenem was as effective as ceftriaxone for
      the initial treatment of complicated UTIs in adults, was generally well
      tolerated, and had a similar overall safety profile.

PMID- 12183245
TI  - Method for estimation of low outer membrane permeability to beta-lactam
      antibiotics.
AB  - The outer membrane of gram-negative bacteria plays a major role in beta-lactam
      resistance as it slows down antibiotic entry into the periplasm and therefore
      acts in synergy with beta-lactamases and efflux systems. Up to now, the
      quantitative estimation of low outer membrane permeability by the method of
      Zimmermann and Rosselet was difficult because of the secreted and cell surface
      associated beta-lactamases. The method presented here uses the acylation of a
      highly sensitive periplasmic penicillin-binding protein (PBP) (BlaR-CTD) to
      assess the rate of beta-lactam penetration into the periplasm. The method is
      dedicated to measurement of low permeability and is only valid when the diffusion
      rate through the outer membrane is rate limiting. Cytoplasmic membrane associated
      PBPs do not interfere since they are acylated after the very sensitive BlaR-CTD.
      This method was used to measure the permeability of beta-lactamase-deficient
      strains of Enterobacter cloacae and Enterobacter aerogenes to benzylpenicillin,
      ampicillin, carbenicillin, cefotaxime, aztreonam, and cephacetrile. Except for
      that of cephacetrile, the permeability coefficients were equal to or below 10(-7)
      cm/s. For cephacetrile, carbenicillin, and benzylpenicillin, the outer membrane
      of E. cloacae was 20 to 60 times less permeable than that of Escherichia coli,
      whereas for cefotaxime, aztreonam, and ampicillin it was, respectively, 400,
      1,000, and 700 times less permeable. The permeability coefficient for aztreonam
      is the lowest ever measured (P = 3.2 x 10(-9) cm/s). Using these values, the MICs
      for a beta-lactamase-overproducing strain of E. cloacae were successfully
      predicted, demonstrating the validity of the method.

PMID- 12183246
TI  - High incidence of cefoxitin and clindamycin resistance among anaerobes in Taiwan.
AB  - Susceptibilities to 16 antimicrobial agents were determined by measurement of
      MICs for 344 isolates of anaerobic bacteria recovered from patients with
      significant infections. Resistance rates varied among antimicrobial agents and
      the species tested. The beta-lactams were more active in gram-positive than in
      gram-negative anaerobes. Resistance to meropenem was low (<1%). For beta-lactam
      beta-lactamase inhibitors, piperacillin-tazobactam was most active for all
      species (resistance, <6%). The rates of resistance to cefoxitin (31 to 65%) and
      clindamycin (50 to 70%) for non-Bacteroides fragilis species of the B. fragilis
      group were higher than those for B. fragilis (4% resistant to cefoxitin and 33%
      resistant to clindamycin). Among members of B. fragilis group, Bacteroides
      thetaiotaomicron was the most resistant to clindamycin (70%) and cefoxitin (65%).
      Rates of susceptibility to imipenem and metronidazole for B. fragilis continue to
      be high compared to those from a previous study 10 years ago. However, resistance
      to metronidazole was found recently in five strains of B. fragilis. We analyzed
      the genetic relationships among the metronidazole-resistant B. fragilis strains
      by pulsed-field gel electrophoresis. The metronidazole-resistant B. fragilis
      strains showed genotypic heterogeneity, excluding the dissemination of a single
      clone.

PMID- 12183247
TI  - Characterization of sparsomycin resistance in Streptomyces sparsogenes.
AB  - The antitumor antibiotic sparsomycin, produced by Streptomyces sparsogenes, is a
      universal translation inhibitor that blocks the peptide bond formation in
      ribosomes from all species. Sparsomycin-resistant strains were selected by
      transforming the sensitive Streptomyces lividans with an S. sparsogenes library.
      Resistance was linked to the presence of a plasmid containing an S. sparsogenes
      5.9-kbp DNA insert. A restriction analysis of the insert traced down the
      resistance to a 3.6-kbp DNA fragment, which was sequenced. The analysis of the
      fragment nucleotide sequence together with the previous restriction data
      associate the resistance to srd, an open reading frame of 1,800 nucleotides.
      Ribosomes from S. sparsogenes and the S. lividans-resistant strains are equally
      sensitive to the inhibitor and bind the drug with similar affinity. Moreover, the
      drug was not modified by the resistant strains. However, resistant cells
      accumulated less antibiotic than the sensitive ones. In addition, membrane
      fractions from the resistant strains showed a higher capacity for binding the
      drug. The results indicate that resistance in the producer strain is not
      connected to either ribosome modification or drug inactivation, but it might be
      related to an alteration in the sparsomycin permeability barrier.

PMID- 12183248
TI  - Consumption of imipenem correlates with beta-lactam resistance in Pseudomonas
      aeruginosa.
AB  - It is generally assumed that the antibiotic prescription policy of a hospital has
      a significant impact on bacterial resistance rates; however, few studies are
      available to support this concept with valid statistical data. During a 3-year
      period from 1997 to 2000, we monitored the consumption of beta-lactam and other
      antibiotics with known activity against Pseudomonas aeruginosa in a 600-bed
      community hospital. Monthly isolations of P. aeruginosa were assessed, and
      resistance rates were recorded. Partial correlation coefficients between
      consumption and resistance rates were determined, taking into account possible
      associations with other variables such as seasonal effects and transfers from
      other hospitals. A total of 30 +/- 7 novel P. aeruginosa strains per month were
      isolated without epidemic clustering. Prescriptions of imipenem varied
      significantly during the study period, while prescriptions of other
      antipseudomonal agents were stable, with the exception of an increase in
      piperacillin-tazobactam prescriptions. Rates of resistance of P. aeruginosa to
      the antimicrobial agents used showed a time course similar to figures for
      imipenem consumption. Monthly rates of resistance to imipenem (partial
      correlation coefficient [cc], 0.63), piperacillin-tazobactam (cc, 0.57), and
      ceftazidime (cc, 0.56) were significantly associated with imipenem prescription
      rates in the same or the preceding month, while consumption of ceftazidime or
      piperacillin-tazobactam had no apparent association with resistance. Among the
      variables investigated, imipenem consumption was identified as the major factor
      associated with both carbapenem and beta-lactam resistance in endemic P.
      aeruginosa. Periods of extensive imipenem use were associated with significant
      increases in resistance. Our data support the concept that a written antibiotic
      policy which balances the use of various antibiotic classes may help to avoid
      disturbances of a hospital's microbial sensitivity patterns.

PMID- 12183249
TI  - Human immunodeficiency virus type 1 genotypic and pharmacokinetic determinants of
      the virological response to lopinavir-ritonavir-containing therapy in protease
      inhibitor-experienced patients.
AB  - The response to regimens including lopinavir-ritonavir (LPV/r) in patients who
      have received multiple protease (PR) inhibitors (PI) can be analyzed in terms of
      human immunodeficiency virus type 1 (HIV-1) genotypic and pharmacokinetic (pK)
      determinants. We studied these factors and the evolution of HIV-1 resistance in
      response to LPV/r in a prospective study of patients receiving LPV/r under a
      temporary authorization in Bordeaux, France. HIV-1 PR and reverse transcriptase
      sequences were determined at baseline LPV/r for all the patients and at month 3
      (M3) and M6 in the absence of response to treatment. pK measurements were
      determined at M1 and M3. Virological failure (VF) was defined as a plasma viral
      load >or=400 copies/ml at M3. A multivariate analysis of the predictors of VF,
      including clinical and biological characteristics and the treatment history of
      the patients, was performed. The PR gene sequence at M0, including individual
      mutations or a previously defined LPV mutation score (D. J. Kempf, J. D.
      Isaacson, M. S. King, S. C. Brun, Y. Xu, K. Real, B. M. Bernstein, A. J. Japour,
      E. Sun, and R. A. Rode, J. Virol. 75:7262-7269, 2001), and the individual
      exposure to LPV were also included covariates. Sixty-eight patients were
      enrolled. Thirty-four percent had a virological response at M3. An LPV mutation
      score of >5 mutations, the presence of the PR I54V mutation at baseline, a high
      number of previous PIs, prior therapy with ritonavir or indinavir, absence of
      coprescription of efavirenz, and a lower exposure to LPV or lower LPV trough
      concentrations were independently associated with VF on LPV/r. Additional PI
      resistance mutations, including primary mutation I50V, could be selected in
      patients failing on LPV/r. Genotypic and pK parameters should be used to optimize
      the virological response to LPV/r in PI-experienced patients and to avoid further
      viral evolution.

PMID- 12183250
TI  - Comparative study of mechanisms of herpes simplex virus inactivation by sodium
      lauryl sulfate and n-lauroylsarcosine.
AB  - The mechanisms of herpes simplex virus (HSV) inactivation by sodium lauryl
      sulfate (SLS) and n-lauroylsarcosine (LS), two anionic surfactants with protein
      denaturant potency, have been evaluated in cultured cells. Results showed that
      pretreatment of HSV type 1 (HSV-1) strain F and HSV-2 strain 333 with either
      surfactant inhibited, in a concentration- and time-dependent manner, their
      infectivities on Vero cells. SLS was a more potent inhibitor of HSV-2 strain 333
      infectivity than LS with respect to the concentration (4.8-fold lower) and time
      (2.4-fold shorter) required to completely inactivate the virus. No inhibition of
      both herpesvirus strains infectivities was observed when Vero cells were
      pretreated with either surfactant. LS prevented the binding of HSV-2 strain 333
      to cells without affecting the stable attachment and the rate of penetration into
      cells, whereas SLS exerted the opposite effect. Both SLS and LS inhibited, in a
      concentration-dependent manner, the HSV-2 strain 333-induced cytopathic effect,
      probably by affecting newly synthesized virions that come into contact with
      surfactant molecules present in culture medium. The pretreatment of HSV-2 strain
      333 with specific combinations of SLS and LS concentrations inhibited the viral
      infectivity in a synergistic manner and resulted in only a small increase in
      their toxicities for exponentially growing Vero cells compared with that caused
      by each compound alone. Taken together, these results suggest that SLS and LS,
      alone or combined, could represent potent candidates as microbicides in topical
      vaginal formulations to prevent the transmission of herpes and possibly other
      pathogens that cause sexually transmitted diseases, including human
      immunodeficiency virus type 1.

PMID- 12183251
TI  - Application of real-time PCR for determination of antiviral drug susceptibility
      of herpes simplex virus.
AB  - A quantitative real-time PCR (TaqMan) assay was developed for determination of
      antiviral drug susceptibility of herpes simplex virus (HSV). After short-time
      culture of the virus, the antiviral drug susceptibility of HSV isolates for
      acyclovir (ACV) was determined by measuring the reduction of the HSV type 1 (HSV
      1) DNA levels in culture supernatants using real-time PCR. The 50% inhibitory
      concentration was reported as the concentration of antiviral drug that reduced
      the number of HSV-1 DNA copies by 50%. A total of 15 well-characterized ACV
      sensitive or -resistant strains and clinical isolates were used for assay
      evaluation. The new assay with real-time PCR readout permitted rapid (3 days),
      objective, and reproducible determination of HSV-1 drug susceptibilities with no
      need for stringent control of initial multiplicity of infection. Furthermore, the
      real-time PCR assay results showed good correlation (r = 0.86) with those for the
      plaque reduction assay. In conclusion, the real-time PCR assay described here is
      a suitable quantitative method for determination of antiviral susceptibility of
      HSV-1, amenable for use in the routine diagnostic virology laboratory.

PMID- 12183252
TI  - Occurrence of antibiotic resistance gene cassettes aac(6')-Ib, dfrA5, dfrA12, and
      ereA2 in class I integrons in non-O1, non-O139 Vibrio cholerae strains in India.
AB  - Molecular mechanisms of multidrug resistance in Vibrio cholerae belonging to non
      O1, non-O139 serogroups isolated during 1997 to 1998 in Calcutta, India, were
      investigated. Out of the 94 strains examined, 22 strains were found to have class
      I integrons. The gene cassettes identified were dfrA1, dfrA15, dfrA5, and dfrA12
      for trimethoprim; aac(6')-Ib for amikacin and tobramycin; aadA1 and aadA2 for
      streptomycin and spectinomycin; and ereA2 for erythromycin resistance. To our
      knowledge, this is the first report of the presence of dfrA5, dfrA12, aac(6')-Ib,
      and ereA2 cassettes in class I integrons of V. cholerae. Forty-three of 94
      strains also had plasmids, and out of these, 14 contained both class I integrons
      and plasmids. Pulsed-field gel electrophoresis followed by Southern hybridization
      revealed that in the 14 plasmid-bearing strains, class I integrons resided either
      on chromosomes, on plasmids, or on both. Our results indicated that besides class
      I integrons and plasmids, a conjugative transposon element, SXT, possibly
      contributed to the multiple antibiotic resistance.

PMID- 12183253
TI  - In vitro selection of resistance in Haemophilus influenzae by amoxicillin
      clavulanate, cefpodoxime, cefprozil, azithromycin, and clarithromycin.
AB  - Abilities of amoxicillin-clavulanate, cefpodoxime, cefprozil, azithromycin, and
      clarithromycin to select resistant mutants of Haemophilus influenzae were tested
      by multistep and single-step methodologies. For multistep studies, 10 random
      strains were tested: 5 of these were beta-lactamase positive. After 50 daily
      subcultures in amoxicillin-clavulanate, MICs did not increase more than fourfold.
      However, cefprozil MICs increased eightfold for one strain. Clarithromycin and
      azithromycin gave a >4-fold increase in 8 and 10 strains after 14 to 46 and 20 to
      50 days, respectively. Mutants selected by clarithromycin and azithromycin were
      associated with mutations in 23S rRNA and ribosomal proteins L4 and L22. Three
      mutants selected by clarithromycin or azithromycin had alterations in ribosomal
      protein L4, while five had alterations in ribosomal protein L22. Two mutants
      selected by azithromycin had mutations in the gene encoding 23S rRNA: one at
      position 2058 and the other at position 2059 (Escherichia coli numbering), with
      replacement of A by G. One clone selected by clarithromycin became
      hypersusceptible to macrolides. In single-step studies azithromycin and
      clarithromycin had the highest mutation rates, while amoxicillin-clavulanate had
      the lowest. All resistant clones were identical to parents as observed by pulsed
      field gel electrophoresis. The MICs of azithromycin for azithromycin-resistant
      clones were 16 to >128 micro g/ml, and those of clarithromycin for clarithromycin
      resistant clones were 32 to >128 micro g/ml in multistep studies. For strains
      selected by azithromycin, the MICs of clarithromycin were high and vice versa.
      After 50 daily subcultures in the presence of drugs, MICs of amoxicillin
      clavulanate and cefpodoxime against H. influenzae did not rise more than
      fourfold, in contrast to cefprozil, azithromycin, and clarithromycin, whose MICs
      rose to variable degrees.

PMID- 12183254
TI  - Antistreptococcal activity of telithromycin compared with seven other drugs in
      relation to macrolide resistance mechanisms in Russia.
AB  - The susceptibilities of 468 recent Russian clinical Streptococcus pneumoniae
      isolates and 600 Streptococcus pyogenes isolates, from 14 centers in Russia, to
      telithromycin, erythromycin, azithromycin, clarithromycin, clindamycin,
      levofloxacin, quinupristin-dalfopristin, and penicillin G were tested. Penicillin
      nonsusceptible S. pneumoniae strains were rare except in Siberia, where their
      prevalence rate was 13.5%: most were penicillin intermediate, but for three
      strains (two from Smolensk and one from Novosibirsk) the MICs of penicillin G
      were 4 or 8 micro g/ml. Overall, 2.5% of S. pneumoniae isolates were resistant to
      erythromycin. Efflux was the prevalent resistance mechanism (five strains;
      41.7%), followed by ribosomal methylation encoded by constitutive erm(B), which
      was found in four isolates. Ribosomal mutation was the mechanism of macrolide
      resistance in three isolates; one erythromycin-resistant S. pneumoniae isolate
      had an A2059G mutation in 23S rRNA, and two isolates had substitution of GTG by
      TPS at positions 69 to 71 in ribosomal protein L4. All S. pyogenes isolates were
      susceptible to penicillin, and 11% were erythromycin resistant. Ribosomal
      methylation was the most common resistance mechanism for S. pyogenes (89.4%).
      These methylases were encoded by erm(A) [subclass erm(TR)] genes, and their
      expression was inducible in 96.6% of isolates. The rest of the erythromycin
      resistant Russian S. pyogenes isolates (7.6%) had an efflux resistance mechanism.
      Telithromycin was active against 100% of pneumococci and 99.2% of S. pyogenes,
      and levofloxacin and quinupristin-dalfopristin were active against all isolates
      of both species.

PMID- 12183255
TI  - Phase I dose escalation trial evaluating the pharmacokinetics, anti-human
      cytomegalovirus (HCMV) activity, and safety of 1263W94 in human immunodeficiency
      virus-infected men with asymptomatic HCMV shedding.
AB  - 1263W94 [maribavir; 5,6-dichloro-2-(isopropylamino)-1,beta-L-ribofuranosyl-1-H
      benzimidazole] is a novel benzimidazole compound for treatment of human
      cytomegalovirus (HCMV) infection and disease, with potent in vitro activity
      against HCMV and good oral bioavailability. A phase I study was conducted to
      determine the pharmacokinetics (PK), anti-HCMV activity, and safety of 1263W94
      administered as multiple oral doses to human immunodeficiency virus type 1
      infected adult male subjects with asymptomatic HCMV shedding. Subjects received
      one of six dosage regimens (100, 200, or 400 mg three times a day, or 600, 900,
      or 1,200 mg twice a day) or a placebo for 28 days. 1263W94 demonstrated linear
      PK, with steady-state plasma 1263W94 profiles predictable based on single-dose
      data. 1263W94 was rapidly absorbed following oral dosing, and values for the
      maximum concentration of the drug in plasma and the area under the concentration
      time curve increased in proportion to the dose. 1263W94 demonstrated in vivo anti
      HCMV activity in semen at all of the dosage regimens tested, with mean reductions
      in semen HCMV titers of 2.9 to 3.7 log(10) PFU/ml among the four regimens
      evaluated for anti-HCMV activity. 1263W94 was generally well tolerated; taste
      disturbance was the most frequently reported adverse event over the 28-day dosing
      period.

PMID- 12183256
TI  - Characterization of a self-transferable plasmid from Salmonella enterica serotype
      typhimurium clinical isolates carrying two integron-borne gene cassettes together
      with virulence and drug resistance genes.
AB  - An unusual self-transferable virulence-resistance plasmid (pUO-StVR2) was found
      in nine multidrug-resistant (ACSSuT phenotype) Salmonella enterica serotype
      Typhimurium clinical isolates that were assigned to four different phage types
      and a single and distinctive XbaI pulsed-field gel electrophoresis profile. pUO
      StVR2 is an IncFII plasmid of about 140 kb in length carrying the spvA, spvB, and
      spvC (Salmonella plasmid virulence) and rck (resistance to complement killing)
      genes. It also carries the oxa1/aadA1a (ampicillin resistance and streptomycin
      spectinomycin resistance) gene cassette configuration located within a class 1
      integron with qacEDelta1/sul1 (ammonium antiseptics resistance and sulfadiazine
      resistance); the transposon genes merA, tnpA, and tnpR (mercury resistance,
      transposase, and resolvase of Tn21, respectively); and the catA1 (chloramphenicol
      resistance) and tet(B) (tetracycline resistance) genes. The insertion of
      resistance genes into a Salmonella virulence plasmid constitutes a new and
      interesting example of plasmid evolution and presents a serious public health
      problem.

PMID- 12183257
TI  - In vitro interaction of flucytosine combined with amphotericin B or fluconazole
      against thirty-five yeast isolates determined by both the fractional inhibitory
      concentration index and the response surface approach.
AB  - Combination therapy could be of benefit for the treatment of invasive yeast
      infections. However, in vitro interaction studies are relatively scarce and the
      interpretation of the fractional inhibitory concentration (FIC) index can be
      contradictory due to various definitions used; not all information on the
      interaction study is used in the index, and different MIC end points exist for
      different classes of drugs. Fitting an interaction model to the whole response
      surface and estimation of an interaction coefficient alpha (IC(alpha)) would
      overcome these objections and has the additional advantage that confidence
      intervals of the interaction are obtained. The efficacy of flucytosine (5FC) in
      combination with amphotericin B (AB) and fluconazole (FCZ) was studied against 35
      yeast isolates in triplicate (Candida albicans [n = 9], Candida glabrata [n = 9],
      Candida krusei [n = 9], and Cryptococcus neoformans [n = 8]) using a broth
      microdilution checkerboard method and measuring growth after 48 h by a
      spectrophotometer. The FIC index and IC(alpha) were determined, the latter by
      estimation from the response surface approach described by Greco et al. (W. R.
      Greco, G. Bravo, and J. C. Parsons, Pharmacol. Rev. 47:331-385, 1995) by using a
      computer program developed for that purpose. For the 5FC-FCZ combination, the
      interactions determined by the IC(alpha) generally were in concordance with the
      interactions determined by the FIC index, but large discrepancies were found
      between both methods for the 5FC-AB combination. These could mainly be explained
      by shortcomings in the FIC approach. The in vitro interaction of 5FC-AB
      demonstrated variable results depending on the tested Candida isolate. In
      general, the 5FC-FCZ combination was antagonistic against Candida species, but
      for some Candida isolates synergism was found. For C. neoformans the interaction
      for both combinations was highly dependent on the tested isolate and the method
      used. Response surface approach is an alternative method for determining the
      interaction between antifungal agents. By using this approach, some of the
      problems encountered with the FIC were overcome.

PMID- 12183258
TI  - Pharmacodynamic assessment of ertapenem (MK-0826) against Streptococcus
      pneumoniae in a murine neutropenic thigh infection model.
AB  - The objective of this study was to determine the susceptibility breakpoint of a
      new carbapenem, ertapenem (MK-0826), against Streptococcus pneumoniae strains
      based on bacterial density and survival studies in a murine thigh infection
      model. Sixteen S. pneumoniae isolates for which MICs ranged from 0.015 to 4.0
      mg/liter were tested with neutropenic ICR mice. Animals were infected with
      bacteria at 10(5) to 10(6) CFU per thigh and were treated with ertapenem starting
      at 2 h postinfection for 4 days. Ertapenem was given subcutaneously at 50 mg/kg
      of body weight every 6 h, which simulates the human pharmacodynamic profile (in
      particular, the duration of time that the concentration of free drug remains
      above the MIC of 2 mg/liter). At 0 and 24 h postinfection, thighs were harvested
      for bacterial density determination. Survival was assessed during 4 days of
      therapy and 3 days after the therapy. A protein binding study was conducted with
      mice by use of the ultrafiltration method. Protein binding in mice was
      approximately 95%, which is comparable to that in humans. The average change in
      bacterial density ranged from -0.22 to -4.4 log CFU per thigh over 24 h compared
      to 0-h controls. The extent of microbial eradication was dependent on the MIC for
      the S. pneumoniae isolate. Substantial bactericidal activities (i.e., killing of
      approximately 2 log CFU per thigh) were consistently observed against isolates
      for which MICs were <or=2 mg/liter, which also resulted in nearly 100% survival
      during the 4 days of drug dosing and 3 days after the therapy. Less-pronounced
      and highly variable bactericidal activities were detected against isolates for
      which the MIC was 4 mg/liter. Substantial enhancement in bactericidal activity
      was observed for CBA/J mice and is attributed to the contribution of the host
      defenses in the immunocompetent species. Assessment of the effectiveness of
      ertapenem by bacterial-density reduction over 24 h and by survival over 4 days of
      therapy in the murine thigh infection model reveals that the drug maintains
      maximal efficacy against S. pneumoniae isolates for which the MIC of this agent
      is <or=2 mg/liter.

PMID- 12183259
TI  - 16S rRNA mutation-mediated tetracycline resistance in Helicobacter pylori.
AB  - Most Helicobacter pylori strains are susceptible to tetracycline, an antibiotic
      commonly used for the eradication of H. pylori. However, an increase in incidence
      of tetracycline resistance in H. pylori has recently been reported. Here the
      mechanism of tetracycline resistance of the first Dutch tetracycline-resistant
      (Tet(r)) H. pylori isolate (strain 181) is investigated. Twelve genes were
      selected from the genome sequences of H. pylori strains 26695 and J99 as
      potential candidate genes, based on their homology with tetracycline resistance
      genes in other bacteria. With the exception of the two 16S rRNA genes, none of
      the other putative tetracycline resistance genes was able to transfer
      tetracycline resistance. Genetic transformation of the Tet(s) strain 26695 with
      smaller overlapping PCR fragments of the 16S rRNA genes of strain 181, revealed
      that a 361-bp fragment that spanned nucleotides 711 to 1071 was sufficient to
      transfer resistance. Sequence analysis of the 16S rRNA genes of the Tet(r) strain
      181, the Tet(s) strain 26695, and four Tet(r) 26695 transformants showed that a
      single triple-base-pair substitution, AGA(926-928)-->TTC, was present within this
      361-bp fragment. This triple-base-pair substitution, present in both copies of
      the 16S rRNA gene of all our Tet(r) H. pylori transformants, resulted in an
      increased MIC of tetracycline that was identical to that for the Tet(r) strain
      181.

PMID- 12183260
TI  - The antifungal echinocandin caspofungin acetate kills growing cells of
      Aspergillus fumigatus in vitro.
AB  - Caspofungin acetate is an antifungal antibiotic that inhibits synthesis of 1,3
      beta-D-glucan, an essential component of the fungal cell wall. While caspofungin
      causes cell death in yeasts and dimorphic fungi such as Candida albicans, its
      effect on Aspergillus fumigatus is less well understood. We used the fluorescent
      dyes 5,(6)-carboxyfluorescein diacetate (CFDA) and bis-(1,3-dibutylbarbituric
      acid) trimethine oxonol (DiBAC), which stain live and dead cells, respectively,
      to further characterize the antifungal activity of caspofungin. For comparison,
      compounds whose mode of action was either fungistatic (fluconazole, itraconazole)
      or fungicidal (amphotericin B) were also evaluated. A correlation between
      caspofungin-induced loss of viability, decreased CFDA staining, and increased
      DiBAC staining was established first with C. albicans. For A. fumigatus,
      caspofungin caused similar dye-staining changes, which were quantified by
      fluorimetric analysis of stained hyphae grown in a medium that promoted dispersed
      growth. The minimum concentration of caspofungin required to produce these
      changes also decreased the level of growth-dependent reduction of the indicator
      dye Alamar Blue. We observed a differential effect of caspofungin as a function
      of cell position: 88% of apical cells and 61% of subapical branching cells failed
      to stain with the viable dye CFDA, but only 24% of subapical cells were
      unstained. Complementary results were seen with germlings from DiBAC-stained,
      caspofungin-treated cultures. Extended incubation of A. fumigatus with a single
      dose of caspofungin affected the same proportion of apical and subapical
      branching cells for up to 72 h. The dye-staining patterns illustrate that the
      cells at the active centers for new cell wall synthesis within A. fumigatus
      hyphae are killed when they are exposed to caspofungin.

PMID- 12183261
TI  - Pharmacokinetic and pharmacodynamic profiles of danofloxacin administered by two
      dosing regimens in calves infected with Mannheimia (Pasteurella) haemolytica.
AB  - The pharmacokinetics and pharmacodynamics of danofloxacin in calves with induced
      Mannheimia (Pasteurella) haemolytica pneumonia were evaluated. Calves received
      either saline as an intravenous (IV) bolus or danofloxacin (0.738 mg/kg of body
      weight) administered as either a single IV bolus or a 36-h continuous IV
      infusion. Blood samples and bronchial secretions were collected before and at
      predetermined times over 48 h following the start of treatment. Calves were
      assessed clinically throughout, and lung consolidation was assessed at necropsy.
      Bronchial secretions and lung tissue were cultured for M. haemolytica. Bolus
      administration of danofloxacin produced a high maximum drug concentration-to-MIC
      ratio (C(max):MIC) of 14.5 and a time period of 9.1 h when plasma danofloxacin
      concentrations exceeded the MIC (T>MIC). Following danofloxacin infusion, the
      C(max):MIC was low (2.3), with a long T>MIC (33.3 h). The area under the curve-to
      MIC ratios were 43.3 and 49.1 for the bolus and infusion administrations,
      respectively. The single bolus of danofloxacin was more effective than the same
      dose administered by continuous infusion, as indicated by a significantly lower
      (P < 0.05) number of animals with M. haemolytica in bronchial secretions after
      treatment and lower rectal temperatures in the 24 h after the start of treatment.
      Thus, danofloxacin exhibited concentration-dependent antimicrobial activity in
      cattle with respiratory disease caused by M. haemolytica.

PMID- 12183262
TI  - Mutation in 23S rRNA associated with macrolide resistance in Neisseria
      gonorrhoeae.
AB  - Fifty-six azithromycin-resistant (MICs, 2.0 to 4.0 micro g/ml) Neisseria
      gonorrhoeae strains with cross-resistance to erythromycin (MICs, 2.0 to 64.0
      micro g/ml), isolated in Canada between 1997 and 1999, were characterized, and
      their mechanisms of azithromycin resistance were determined. Most (58.9%) of them
      belonged to auxotype-serotype class NR/IB-03, with a 2.6-mDa plasmid. Based on
      resistance to crystal violet (MICs >or= 1 micro g/ml), 96.4% of these macrolide
      resistant strains appeared to have increased efflux. Nine of the eleven strains
      selected for further characterization were found to have a promoter region mtrR
      mutation, a single-base-pair (A) deletion in the 13-bp inverted repeat, which is
      believed to cause overexpression of the mtrCDE-encoded efflux pump. The two
      remaining macrolide-resistant strains (erythromycin MIC, 64.0 micro g/ml;
      azithromycin MIC, 4.0 micro g/ml), which did not have the mutation in the mtrR
      promoter region, were found to have a C2611T mutation (Escherichia coli
      numbering) in the peptidyltransferase loop in domain V of the 23S rRNA alleles.
      Although mutations in domain V of 23S rRNA alleles had been reported in other
      bacteria, including E. coli, Streptococcus pneumoniae, and Helicobacter pylori,
      this is the first observation of these mutations associated with macrolide
      resistance in N. gonorrhoeae.

PMID- 12183263
TI  - Antibiotic pharmacodynamics in surgical prophylaxis: an association between
      intraoperative antibiotic concentrations and efficacy.
AB  - The objective of this study was to characterize the relationship between
      gentamicin concentrations during surgery and the development of wound infection
      following colorectal operations. Despite decades of research in surgical
      prophylaxis, the relationship between intraoperative antibiotic concentrations
      and postoperative infection and the concentrations required for effective
      prophylaxis have not been established. A pharmacodynamic analysis was conducted
      using data from a previous prospective, randomized, double-blind clinical study
      which compared two dosage regimens of gentamicin plus metronidazole for
      prophylaxis in connection with elective colorectal surgery. Univariate and
      multivariate analyses of risk factors for postoperative wound infection were
      conducted, and the relationship between intraoperative gentamicin concentrations
      and surgical outcome was characterized. The gentamicin concentration at the time
      of surgical closure was one of the strongest independent risk factors for
      infection (P = 0.02), along with the presence of diabetes mellitus (P = 0.02),
      stoma (P = 0.04), and advanced age (P = 0.05). Gentamicin concentrations at
      closure of less than 0.5 mg/liter were associated with an infection rate of 80%
      (representing 8 of 10 patients with concentrations below that level) (P = 0.003).
      Receiver operating characteristic curve analysis identified a critical closure
      concentration of 1.6 mg/liter for effective surgical prophylaxis (P = 0.002;
      sensitivity, 70.8%; specificity, 65.9%). This study provides new and important
      information on antibiotic pharmacodynamics in surgical prophylaxis. It
      demonstrates the critical effect of the antibiotic concentration at closure on
      wound infection and suggests a significant association between the concentration
      and other well-established risk factors, like the timing of preoperative
      antibiotic administration and surgery duration.

PMID- 12183264
TI  - Prospective survey of beta-lactamases produced by ceftazidime- resistant
      Pseudomonas aeruginosa isolated in a French hospital in 2000.
AB  - In 2000, at the Universite d'Auvergne teaching hospital in Clermont-Ferrand,
      France, 44 (6.2%) strains of Pseudomonas aeruginosa were found to be resistant to
      ceftazidime. After genotyping, 34 strains were selected. Nine had an additional
      beta-lactamase: OXA-21 (n = 6), PSE-1 (CARB-2) (n = 2), or PER-1 (n = 1).
      Ceftazidime resistance was related solely to the overproduction of the
      cephalosporinase in 30 strains. Sequencing of five bla(AmpC) genes encoding
      cephalosporinases with different pIs showed 99% identity with the ampC gene of P.
      aeruginosa PAO1.

PMID- 12183265
TI  - Predicting evolution by in vitro evolution requires determining evolutionary
      pathways.
AB  - In an early example of DNA shuffling, Stemmer (W. P. C. Stemmer, Nature 370:389
      390, 1994) demonstrated a dramatic improvement in the activity of the TEM-1 beta
      lactamase toward cefotaxime as the consequence of six amino acid substitutions.
      It has been pointed out (B. G. Hall, FEMS Microbiol. Lett. 178:1-6, 1999; M. C.
      Orencia, J. S. Yoon, J. E. Ness, W. P. Stemmer, and R. C. Stevens, Nat. Struct.
      Biol. 8:238-242, 2001) that the power of DNA shuffling might be applied to the
      problem of predicting evolution in nature from in vitro evolution in the
      laboratory. As a predictor of natural evolutionary processes, that power may be
      misleading because in nature mutations almost always arise one at a time, and
      each advantageous mutation must be fixed into the population by an evolutionary
      pathway that leads from the wild type to the fully evolved sequence. Site
      directed mutagenesis was used to introduce each of Stemmer's six substitutions
      into TEM-1, the best single mutant was chosen, and each of the remaining five
      substitutions was introduced. Repeated rounds of site-directed mutagenesis and
      selection of the best mutant were used in an attempt to construct a pathway
      between the wild-type TEM-1 and Stemmer's mutant with six mutations. In the
      present study it is shown (i) that no such pathway exists between the wild-type
      TEM-1 and the supereffective cefotaxime-hydrolyzing mutant that was generated by
      six amino acid substitutions via DNA shuffling (Stemmer, Nature 370:389-390,
      1994) but that a pathway to a fourfold more efficient enzyme resulting from four
      of the same substitutions does exist, and (ii) that the more efficient enzyme is
      likely to arise in nature as the result of a single mutation in the naturally
      occurring TEM-52 allele.

PMID- 12183266
TI  - In vitro interaction of caspofungin acetate with voriconazole against clinical
      isolates of Aspergillus spp.
AB  - The interaction between caspofungin acetate and voriconazole was studied in vitro
      by using 48 clinical Aspergillus spp. isolates obtained from patients with
      invasive aspergillosis. MICs were determined by the NCCLS broth microdilution
      method. Synergy, defined as a fractional inhibitory concentration (FIC) index of
      <1, was detected in 87.5% of the interactions; an additive effect, defined as an
      FIC index of 1.0, was observed in 4.2% of the interactions; and a subadditive
      effect, defined as an FIC index of 1.0 to 2.0, was found in 8.3% of the
      interactions. No antagonism was observed. Animal models are required to validate
      the in vivo significance of these in vitro data presented for the combination of
      caspofungin and voriconazole.

PMID- 12183267
TI  - Surveillance for antiviral-agent-resistant herpes simplex virus in the general
      population with recurrent herpes labialis.
AB  - In a general population survey in the United States, the prevalence of antiviral
      agent-resistant herpes simplex virus was very low among more than 1,000 isolates
      from individuals with an episode of recurrent herpes labialis not treated with
      topical antiviral agents. Two isolates had borderline resistance to acyclovir
      (0.2%), and all were susceptible to penciclovir.

PMID- 12183268
TI  - Beta-lactamases of Kluyvera ascorbata, probable progenitors of some plasmid
      encoded CTX-M types.
AB  - Kluyvera ascorbata produces a beta-lactamase that results in an atypical
      susceptibility pattern, including low-level resistance to penicillins,
      cephalothin, and cefuroxime, but this resistance is reversed by clavulanate. Ten
      nucleotide sequences of the corresponding gene, bla(KLUA), were obtained and were
      found to have minor variations (96 to 100%). Otherwise, bla(KLUA) was found to be
      similar (95 to 100%) to some plasmid-encoded CTX-M-type beta-lactamases. Finally,
      mobilization of bla(KLUA) on a plasmid was found to be mediated probably by a
      genetic mobile element like ISEcp1.

PMID- 12183269
TI  - Functional characterization of Brucella melitensis NorMI, an efflux pump
      belonging to the multidrug and toxic compound extrusion family.
AB  - Two putative proteins (NorMI and NorMII) similar to the multidrug efflux protein
      NorM of Vibrio parahaemolyticus are encoded by the Brucella melitensis 16 M
      genome. We show that a drug-hypersusceptible Escherichia coli strain
      overexpressing NorMI displays increased resistance to norfloxacin, ciprofloxacin,
      gentamicin, tetraphenylphosphonium ion, acriflavine, and berberine. This elevated
      resistance was proven to be mediated by an energy-dependent efflux mechanism.
      NorMI belongs to the multidrug and toxic compound extrusion family and is the
      first multidrug efflux protein identified in Brucella spp.

PMID- 12183270
TI  - Clinical isolates of Staphylococcus aureus with ribosomal mutations conferring
      resistance to macrolides.
AB  - Six strains of Staphylococcus aureus isolated from cystic fibrosis patients after
      treatment with azithromycin were cross-resistant to azithromycin and
      erythromycin. None of the isolates contained erm or msr(A) genes, but they all
      carried either A2058G/U or A2059G mutations within the rrl genes, with a majority
      of the rRNA copies bearing the mutation. One strain displayed an additional
      mutation in the rplV gene, encoding the L22 ribosomal protein.

PMID- 12183272
TI  - Efficacies of quinupristin-dalfopristin combined with vancomycin in vitro and in
      experimental endocarditis due to methicillin-resistant Staphylococcus aureus in
      relation to cross-resistance to macrolides, lincosamides, and streptogramin B-
      type antibiotics.
AB  - A beneficial effect of the combination of quinupristin-dalfopristin and
      vancomycin was observed against two methicillin-resistant strains of
      Staphylococcus aureus harboring or not harboring the ermC gene, which codes for
      constitutive macrolide, lincosamide, and streptogramin B resistance. The
      beneficial effect was observed in time-kill studies, in which the drugs were used
      at inhibitory concentrations, and in a rabbit model of endocarditis, in which the
      combination was highly bactericidal and more active than monotherapies.

PMID- 12183271
TI  - Phenylpropenamide derivatives AT-61 and AT-130 inhibit replication of wild-type
      and lamivudine-resistant strains of hepatitis B virus in vitro.
AB  - The phenylpropenamide derivatives AT-61 and AT-130 are nonnucleoside analogue
      inhibitors of hepatitis B virus (HBV) replication. They inhibited the replication
      of wild-type HBV with 50% inhibitory concentrations of 21.2 +/- 9.5 and 2.40 +/-
      0.92 micro M, respectively, compared to 0.064 +/- 0.020 micro M lamivudine. There
      were no significant differences in sensitivity between wild-type and nucleoside
      analogue-resistant (rtL180M, rtM204I, and rtL180M + rtM204V) HBV.

PMID- 12183274
TI  - In vitro activities of garenoxacin (BMS-284756) against 170 clinical isolates of
      nine Pasteurella species.
AB  - The in vitro susceptibilities of 170 clinical isolates plus 12 American Type
      Culture Collection strains of Pasteurella species comprising nine species and
      three Pasteurella multocida subspecies were studied by an agar dilution method.
      Garenoxacin (BMS-284756), a new des-fluoro(6) quinolone, was active at <or=0.06
      micro g/ml against all isolates, including four beta-lactamase-producing strains,
      with >90% of the strains susceptible to <or=0.008 micro g/ml. Garenoxacin was
      generally 1 to 2 dilutions more active than levofloxacin and moxifloxacin and was
      the most active agent tested. Cefoxitin required 1 micro g/ml for inhibition of
      51 of 182 (29%) of strains, and 3 strains (also beta-lactamase producers) were
      resistant to doxycycline.

PMID- 12183273
TI  - Antibiotic susceptibilities of Parachlamydia acanthamoeba in amoebae.
AB  - Parachlamydia acanthamoeba are intracellular bacteria of amoebae and are
      considered potential etiological agents of human pneumonia. We have determined
      the in vitro antibiotic susceptibilities of two strains (strain Bn(9) and Hall's
      coccus) in Acanthamoeba polyphaga. The two strains were susceptible to
      tetracyclines, macrolides, and rifampin, but resistant to fluoroquinolones.

PMID- 12183275
TI  - In vitro and in vivo antibacterial activities of DW286, a new fluoronaphthyridone
      antibiotic.
AB  - The in vitro and in vivo activities of DW286, a novel fluoronaphthyridone with
      potent antibacterial activity, were compared with those of ciprofloxacin,
      gemifloxacin, sparfloxacin, and trovafloxacin. Against gram-positive bacteria,
      such as Staphylococcus aureus, Staphylococcus epidermidis, Streptococcus
      pneumoniae, and Enterococcus faecalis, the in vitro activity of DW286 was
      stronger than that of any other reference antibiotic. Against gram-negative
      bacteria, the activity of DW286 was similar to those of trovafloxacin and
      gemifloxacin but was weaker than that of ciprofloxacin. In a mouse systemic
      infection caused by three S. aureus strains, including methicillin-resistant S.
      aureus and quinolone-resistant S. aureus (QRSA), DW286 demonstrated the most
      potent activity, as found in vitro. Specially, DW286 is >or=8-fold more active
      against QRSA than the other fluoroquinolones. And the 50% protective doses for
      DW286 were correspondent with the in vitro activities.

PMID- 12183276
TI  - Prevalence of protease and reverse transcriptase drug resistance mutations over
      time in drug-naive human immunodeficiency virus type 1-positive individuals in
      Rio de Janeiro, Brazil.
AB  - The prevalence of mutations that confer resistance to protease inhibitors and to
      nucleoside and nonnucleoside reverse transcriptase inhibitors in 49 blood samples
      from drug-naive human immunodeficiency virus type 1-infected blood donors living
      in Rio de Janeiro state, Brazil, in 1998 was evaluated genotypically and
      phenotypically.

PMID- 12183277
TI  - Effect of lamivudine on transmission of human T-cell lymphotropic virus type 1 to
      adult peripheral blood mononuclear cells in vitro.
AB  - The effects of lamivudine (3TC) on in vitro infection of peripheral blood
      mononuclear cells (PBMC) from healthy donors with human T-cell lymphotropic virus
      type 1 (HTLV-1) were investigated. Direct measures of viral replication (viral
      DNA, RNA, and protein) all gave similar, very high 50% inhibitory concentrations
      in comparison with those previously reported for zidovudine. Nevertheless, 3TC
      inhibited HTLV-1-driven long-term growth of infected PBMC in vitro at
      concentrations (6.25 micro M) which had poor or no direct antiviral effects,
      suggesting that another mechanism may be playing a role.

PMID- 12183278
TI  - Comparative evaluation of disk diffusion with microdilution assay in
      susceptibility testing of caspofungin against Aspergillus and Fusarium isolates.
AB  - We compared the disk diffusion and broth microdilution methods for susceptibility
      testing of caspofungin against Aspergillus (n = 78) and Fusarium (n = 22)
      isolates. Microdilution testing followed the NCCLS M-38P guidelines but was
      performed in antibiotic medium 3 supplemented to 2% glucose (AM3). Disk diffusion
      assays were performed on AM3 agar plates with a 2- micro g caspofungin disk. By
      both methods, caspofungin showed favorable activity against Aspergillus isolates
      and no activity against Fusarium isolates. In the disk-based format, intrazonal
      growth that was not influenced by the drug concentration gradient was
      consistently observed for all of the Aspergillus isolates tested.

PMID- 12183279
TI  - Incidence of high-level evernimicin resistance in Enterococcus faecium among food
      animals and humans.
AB  - Six high-level evernimicin-resistant Enterococcus faecium isolates were
      identified among 304 avilamycin-resistant E. faecium isolates from animals and
      404 stool samples from humans with diarrhea. All four animal isolates, and one of
      the human isolates, were able to transfer resistance to a susceptible E. faecium
      strain. The resulting transconjugants all tested positive for the presence of
      emtA, a gene encoding a methyltransferase previously linked with high-level
      evernimicin resistance. The four transconjugants derived from animal isolates all
      carried the same plasmid, while a differently sized plasmid was found in the
      isolate from humans. This study demonstrated a low incidence of high-level
      evernimicin resistance mediated by the emtA gene in different E. faecium isolates
      of animal and human origin.

PMID- 12183280
TI  - Voriconazole inhibition of the metabolism of tacrolimus in a liver transplant
      recipient and in human liver microsomes.
AB  - The purpose of this study was to assess the effect of voriconazole on the blood
      tacrolimus concentration in a liver transplant recipient and to examine the
      interaction between voriconazole and tacrolimus by using human liver microsomes.
      Two subjects were enrolled in the clinical study: one received voriconazole, and
      the other received a placebo. Tacrolimus metabolism was evaluated in human liver
      microsomes at various concentrations in the absence and presence of various
      concentrations of voriconazole. Coadministration of voriconazole and tacrolimus
      resulted in elevated (nearly 10-fold-higher) trough tacrolimus blood
      concentrations in the liver transplant patient. In the in vitro study,
      voriconazole at a concentration of 10.4 +/- 4.3 micro g/ml inhibited the
      metabolism of tacrolimus by 50%. Clinically relevant concentrations of
      voriconazole inhibited the metabolism of tacrolimus in human liver microsomes.
      Close monitoring of the blood concentration and adjustment in the dose of
      tacrolimus are warranted in transplant recipients treated with voriconazole.

PMID- 12183281
TI  - Comparative activities of the oxazolidinone AZD2563 and linezolid against
      selected recent North American isolates of Streptococcus pneumoniae.
AB  - The activity of AZD2563 against 250 highly resistant pneumococci and 267 drug
      susceptible isolates was determined. The AZD2563 MICs for 50 and 90% of the
      strains tested were 1 and 2 micro g/ml and 0.5 and 1 micro g/ml, respectively,
      for the two isolate groups. These MICs were within 1 log(2) dilution of those of
      linezolid.

PMID- 12183282
TI  - Effect of the echinocandin caspofungin on expression of Candida albicans
      secretory aspartyl proteinases and phospholipase in vitro.
AB  - Although the echinocandin caspofungin primarily inhibits the synthesis of cell
      wall 1,3-beta-D-glucan, its fungicidal activity could also potentially perturb
      the expression of virulence factors involved in the ability of Candida albicans
      to cause infection. Expression of the C. albicans secretory aspartyl proteinase
      (SAP) and phospholipase B (PLB) virulence genes was determined by reverse
      transcription-PCR after the addition of caspofungin to cells grown for 15 h in
      Sabouraud dextrose broth. In cells that remained viable, expression of SAP1 to
      SAP3, SAP7 to SAP9, and PLB1 was unaltered after exposure to fungicidal
      concentrations (4 to 16 micro g/ml) of caspofungin over a period of 7 h. However,
      expression of SAP5 increased steadily beginning 1 h after exposure to
      caspofungin. These results indicate that caspofungin is rapidly fungicidal
      against C. albicans, before any suppression of SAP or PLB1 gene expression can
      occur.

PMID- 12183283
TI  - Development of a yeast assay for rapid screening of inhibitors of human-derived
      Pneumocystis carinii dihydrofolate reductase.
AB  - Human-derived Pneumocystis carinii dihydrofolate reductase (DHFR) was expressed
      in a Saccharomyces cerevisiae strain whose growth depends on complementation by
      this enzyme. We utilized a quantitative assay to measure the sensitivity of this
      yeast strain to DHFR inhibitors. This assay should be useful for identifying new
      inhibitors of human-derived P. carinii DHFR.

PMID- 12183284
TI  - Prevalence of oxacillin resistance in Staphylococcus aureus among inpatients and
      outpatients in the United States during 2000.

PMID- 12183285
TI  - Relationship between antibiotic resistance in Streptococcus pneumoniae and that
      in Haemophilus influenzae: evidence for common selective pressure.

PMID- 12183286
TI  - gyrA Mutations associated with nalidixic acid-resistant salmonellae from wild
      birds.

PMID- 12183287
TI  - Amino acid substitutions at position 69 of the reverse transcriptase of human
      immunodeficiency virus type 1 are frequent in zalcitabine-naive antiretroviral
      drug-experienced patients.

PMID- 12183289
TI  - New outbreak of legionnaires' disease in the United Kingdom.

PMID- 12183290
TI  - Bone marrow transplants.

PMID- 12183291
TI  - The NHS, the private sector, and the virtual asylum.

PMID- 12183292
TI  - Physical activity for preventing strokes.

PMID- 12183295
TI  - Researchers question ethics of diabetes drug trial.

PMID- 12183296
TI  - Psychiatrists, lawyers, and service users unite against proposed bill.

PMID- 12183298
TI  - Pesticide ban imposed after reports of congenital abnormalities.

PMID- 12183299
TI  - Dutch GPs call for ban on Novartis products.

PMID- 12183300
TI  - Famine relief must also tackle health care.

PMID- 12183304
TI  - Medical centre recalls potentially infected body parts.

PMID- 12183305
TI  - Randomised study of long term outcome after epidural versus non-epidural
      analgesia during labour.
AB  - OBJECTIVE: To determine whether epidural analgesia during labour is associated
      with long term backache. DESIGN: Follow up after randomised controlled trial.
      Analysis by intention to treat. SETTING: Department of obstetrics and gynaecology
      at one NHS trust. PARTICIPANTS: 369 women: 184 randomised to epidural group
      (treatment as allocated received by 123) and 185 randomised to non-epidural group
      (treatment as allocated received by 133). In the follow up study 151 women were
      from the epidural group and 155 from the non-epidural group. MAIN OUTCOME
      MEASURES: Self reported low back pain, disability, and limitation of movement
      assessed through one to one interviews with physiotherapist, questionnaire on
      back pain and disability, physical measurements of spinal mobility. RESULTS:
      There were no significant differences between groups in demographic details or
      other key characteristics. The mean time interval from delivery to interview was
      26 months. There were no significant differences in the onset or duration of low
      back pain, with nearly a third of women in each group reporting pain in the week
      before interview. There were no differences in self reported measures of
      disability in activities of daily living and no significant differences in
      measurements of spinal mobility. CONCLUSIONS: After childbirth there are no
      differences in the incidence of long term low back pain, disability, or movement
      restriction between women who receive epidural pain relief and women who receive
      other forms of pain relief.

PMID- 12183306
TI  - Birth weight of offspring and insulin resistance in late adulthood: cross
      sectional survey.
AB  - OBJECTIVE: To investigate the association between birth weight of offspring and
      mothers' insulin resistance in late adulthood. DESIGN: Cross sectional survey.
      SETTING: General practitioner's surgeries in 23 towns in Great Britain.
      PARTICIPANTS: 4286 women aged 60-79 years. MAIN OUTCOME MEASURES: Maternal
      insulin resistance. RESULTS: Birth weight of offspring was inversely related to
      maternal insulin resistance in late adulthood. For each 1 kg higher birth weight
      of offspring, women had a 15% reduction in the odds of being in the fourth with
      highest insulin resistance, compared to other fourths (odds ratio 0.85; 95%
      confidence interval 0.71 to 1.00). This increased to 27% (0.73; 0.60 to 0.90)
      after adjusting data for potential confounders. A U shaped relation between birth
      weight of offspring and diabetes in older age was found; women with the lightest
      and heaviest offspring had the highest prevalence of diabetes. CONCLUSIONS: Birth
      weight of offspring is inversely related to the mother's insulin resistance in
      late adulthood, despite the association of glucose intolerance during pregnancy
      with heavier offspring at birth. Common genetic factors contribute to the
      relation between birth weight and risk of cardiovascular disease and diabetes in
      adults.

PMID- 12183308
TI  - Acquisition of W135 meningococcal carriage in Hajj pilgrims and transmission to
      household contacts: prospective study.

PMID- 12183307
TI  - Efficacy of handrubbing with alcohol based solution versus standard handwashing
      with antiseptic soap: randomised clinical trial.
AB  - OBJECTIVE: To compare the efficacy of handrubbing with an alcohol based solution
      versus conventional handwashing with antiseptic soap in reducing hand
      contamination during routine patient care. DESIGN: Randomised controlled trial
      during daily nursing sessions of 2 to 3 hours. SETTING: Three intensive care
      units in a French university hospital. PARTICIPANTS: 23 healthcare workers.
      INTERVENTIONS: Handrubbing with alcohol based solution (n=12) or handwashing with
      antiseptic soap (n=11) when hand hygiene was indicated before and after patient
      care. Imprints taken of fingertips and palm of dominant hand before and after
      hand hygiene procedure. Bacterial counts quantified blindly. MAIN OUTCOME
      MEASURES: Bacterial reduction of hand contamination. RESULTS: With handrubbing
      the median percentage reduction in bacterial contamination was significantly
      higher than with handwashing (83% v 58%, P=0.012), with a median difference in
      the percentage reduction of 26% (95% confidence interval 8% to 44%). The median
      duration of hand hygiene was 30 seconds in each group. CONCLUSIONS: During
      routine patient care handrubbing with an alcohol based solution is significantly
      more efficient in reducing hand contamination than handwashing with antiseptic
      soap.

PMID- 12183310
TI  - Comparison of specialty referral rates in the United Kingdom and the United
      States: retrospective cohort analysis.

PMID- 12183309
TI  - Cluster randomised controlled trial of tailored interventions to improve the
      management of urinary tract infections in women and sore throat.
AB  - OBJECTIVE: To assess the effectiveness of tailored interventions to implement
      guidelines for urinary tract infections in women and sore throat. DESIGN:
      Unblinded, cluster randomised pretest-post-test trial. SETTING: 142 general
      practices in Norway. PARTICIPANTS: 72 practices received interventions to
      implement guidelines for urinary tract infection and 70 practices received
      interventions to implement guidelines for sore throat, serving as controls for
      each other. 59 practices in the urinary tract infection group and 61 practices in
      the sore throat group completed the study. Outcomes were measured in 16 939
      consultations for sore throat and 9887 consultations for urinary tract infection.
      INTERVENTIONS: Interventions were developed to overcome identified barriers to
      implementing the guidelines. The main components of the tailored interventions
      were patient educational material, computer based decision support and reminders,
      an increase in the fee for telephone consultations, and interactive courses for
      general practitioners and practice assistants. MAIN OUTCOME MEASURES: Changes in
      rates of use of antibiotics, laboratory tests, and telephone consultations.
      RESULTS: Patients in the sore throat group were 3% less likely to receive
      antibiotics after the intervention. Women with symptoms of urinary tract
      infection in the intervention group were 5.1% less likely to have a laboratory
      test ordered. No significant differences were found between the groups for the
      other outcomes. Large variation was found across the included practices in the
      rates of antibiotic prescription, use of laboratory tests and telephone
      consultations, and in the extent of change for all three outcome measures.
      CONCLUSIONS: Passively delivered, complex interventions targeted at identified
      barriers to change had little effect in changing practice.

PMID- 12183311
TI  - The therapeutic potential of stem cells from adults.

PMID- 12183312
TI  - Cancer.

PMID- 12183313
TI  - Systematic reviews and lifelong diseases.

PMID- 12183314
TI  - Creating a medical school for Malawi: problems and achievements.

PMID- 12183315
TI  - Consultations do not have to be longer.

PMID- 12183316
TI  - Patients should receive copies of letters and summaries.

PMID- 12183317
TI  - Use of Swiss paediatric emergency department has grown.

PMID- 12183318
TI  - Emergency medicine. Whole system is responsible for solving overcrowding of
      departments.

PMID- 12183319
TI  - GPs mustn't be dismayed about grasp of cognitive therapy.

PMID- 12183320
TI  - Bread is fortified with folic acid in Hungary.

PMID- 12183321
TI  - Authors respond to criticism of rheumatoid arthritis twin study.

PMID- 12183322
TI  - Grading referrals to specialist breast units. Guidance on referral needs to be
      evidence based.

PMID- 12183323
TI  - General perception of stroke. Knowledge of stroke is lacking.

PMID- 12183324
TI  - Licensing system for doctors. Licensing seems inevitable, but is it necessary?

PMID- 12183325
TI  - Characterization of GABA(A) receptor ligands in the rat cortical wedge
      preparation: evidence for action at extrasynaptic receptors?
AB  - 1. GABA(A) receptor agonists have previously been characterized at human GABA(A)
      receptors expressed in Xenopus oocytes. The correlation between these data and
      functional in vivo data of 4,5,6,7-tetrahydroisoxazolo[5,4-c]pyridin-3-ol (THIP)
      has shown that THIP is 100 fold more potent in clinical studies than in oocytes.
      2. THIP and a series of agonists (GABA, Isoguvacine), partial agonists (Imidazole
      acetic acid; P4S, 4-PIOL, thio-4-PIOL) and one antagonist (SR95531) were
      characterized in the rat cortical wedge preparation using inhibition of
      spontaneous activity in Mg(++) free medium as the measurable parameter. 3.
      Agonists were in general 40 times more potent in the wedge preparation than at
      alpha(1)beta(3)gamma(2s) containing receptors expressed in Xenopus oocytes,
      whereas the antagonist was equipotent under these two conditions. 4. Partial
      agonists with responses above 6% at alpha(1)beta(3)gamma(2s) containing receptors
      were full agonists in the rat cortical wedge preparation, whereas partial
      agonists with maximum responses below 6% behaved as partial agonists in the rat
      cortical wedge preparation. 5. These data suggest that only a small fraction of
      the GABA(A) receptors in the rat cortical wedge needs to be activated by GABA(A)
      agonists in order to obtain a maximum response. Results therefore indicate a
      significant contribution of extrasynaptic receptors to pharmacological activity
      of exogenous applied GABA(A) agonists in this system.

PMID- 12183326
TI  - Characterization of the beta-adrenoceptor subtype involved in mediation of
      glucose transport in L6 cells.
AB  - 1. The receptor that mediates the increase in glucose transport (GT) in response
      to beta-adrenoceptor (beta-AR) agonists was characterized in the rat skeletal
      muscle cell line L6, using the 2-deoxy-[(3)H]-D-glucose assay. 2. The beta(3)-AR
      agonist BRL37344 (pEC(50) = 6.89 +/- 0.21), the beta-AR agonist isoprenaline
      (pEC(50) = 8.99 +/ -0.24) and the beta(2)-AR agonist zinterol (pEC(50) = 9.74 +/-
      0.15) increased GT as did insulin (pEC(50) = 6.93 +/- 0.15). The highly selective
      beta(3)-AR agonist CL316243 only weakly stimulated GT. 3. The pK(B) values
      calculated from the shift of the pEC(50) values of the agonists in the presence
      of the beta(1)-AR selective antagonist CGP 20712A or the beta(3)-AR selective
      antagonist SR 59230A were not indicative of activation of beta(1)- or beta(3)
      ARs. Only (-)-propranolol and the beta(2)-AR selective antagonist ICI 118551
      caused marked rightward shifts of CR curves to isoprenaline (pK(B) = 10.2 +/- 0.2
      and 9.6 +/- 0.3), zinterol (pK(B) = 9.0 +/- 0.1 and 9.4 +/- 0.3) and BRL 37344
      (pK(B) = 9.4 +/- 0.3 and 8.4 +/- .2), indicating participation of beta(2)-ARs. 4.
      The pharmacological analysis was supported by reverse transcription and
      polymerase chain reaction analysis of L6 mRNA, which showed high levels of
      expression of beta(2)-AR but not beta(1)- or beta(3)-AR in these cells. 5.
      Forskolin and dibutyryl cyclic AMP produced negligible increases in GT while the
      phosphatidylinositol-3 kinase inhibitor, wortmannin, significantly decreased both
      insulin- and zinterol-stimulated GT, suggesting a possible interaction between
      the insulin and beta(2)-AR pathways. 6. This study demonstrates that beta(2)-ARs
      mediate the increase in GT in L6 cells to beta-AR agonists, including the beta(3)
      AR selective agonist BRL 37344. This effect does not appear to be directly
      related to increases in cyclic AMP but requires P13K.

PMID- 12183328
TI  - An N-terminal histidine regulates Zn(2+) inhibition on the murine GABA(A)
      receptor beta3 subunit.
AB  - 1. Whole-cell currents were recorded from Xenopus laevis oocytes and human
      embryonic kidney cells expressing GABA(A) receptor beta3 subunit homomers to
      search for additional residues affecting Zn(2+) inhibition. These residues would
      complement the previously identified histidine (H267), present just within the
      external portal of the ion channel, which modulates Zn(2+) inhibition. 2. Zinc
      inhibited the pentobarbitone-gated current on beta3(H267A) homomers at pH 7.4,
      but this effect was abolished at pH 5.4. The Zn(2+)-sensitive spontaneous beta3
      subunit-mediated conductance was also insensitive to block by Zn(2+) at pH 5.4.
      3. Changing external pH enabled the titration of the Zn(2+) sensitive binding
      site or signal transduction domain. The pK(a) was estimated at 6.8 +/- 0.03
      implying the involvement of histidine residues. 4. External histidine residues in
      the beta3 receptor subunit were substituted with alanine, in addition to the
      background mutation, H267A, to assess their sensitivity to Zn(2+) inhibition. The
      Zn(2+) IC(50) was unaffected by either the H119A or H191A mutations. 5. The
      remaining histidine, H107, the only other candidate likely to participate in
      Zn(2+) inhibition, was substituted with various residues. Most mutants were
      expressed at the cell surface but they disrupted functional expression of beta3
      homomers. However, H107G was functional and demonstrated a marked reduction in
      sensitivity to Zn(2+). 6. GABA(A) receptor beta3 subunits form functional ion
      channels that can be inhibited by Zn(2+). Two histidine residues are largely
      responsible for this effect, H267 in the pore lining region and H107 residing in
      the extracellular N-terminal domain.

PMID- 12183327
TI  - Endothelial nitric oxide modulates perivascular sensory neurotransmission in the
      rat isolated mesenteric arterial bed.
AB  - 1. A possible role of nitric oxide (NO) as a modulator of capsaicin-sensitive
      sensory neurotransmission in blood vessels was investigated in the rat isolated
      mesenteric arterial bed. 2. Electrical field stimulation (EFS) of methoxamine
      preconstricted mesenteric beds elicited frequency-dependent vasorelaxation
      mediated by capsaicin-sensitive sensory nerves. N(G)-nitro-L-arginine methyl
      ester (L-NAME, 10 and 300 microM) and 7-nitroindazole (7-NI, 100 microM),
      inhibitors of nitric oxide synthase (NOS), augmented sensory neurogenic
      vasorelaxation. D-NAME (300 microM), 6-aminoindazole (100 microM) and N(omega)
      propyl-L-arginine (50 nM), a selective inhibitor of neuronal NOS, were without
      effect. The effect of 10 microM L-NAME was reversed by L-arginine (1 mM), the
      substrate for NOS. 3. L-NAME (300 microM) and 7-NI (100 microM) had no
      significant effect on vasorelaxations to calcitonin gene-related peptide (CGRP),
      the principal motor neurotransmitter of capsaicin-sensitive sensory nerves in rat
      mesenteric arteries, or to capsaicin, indicating a prejunctional action. The
      inhibitors of NOS had no effect on vasorelaxation to forskolin, but augmented
      vasorelaxation to sodium nitroprusside (SNP). 4. Removal of the endothelium
      augmented sensory neurogenic vasorelaxation, but did not affect vasorelaxation to
      CGRP, indicating a prejunctional action of endothelial NO. 5. In the absence of
      endothelium, L-NAME (300 microM) inhibited, and 7-NI (100 microM) caused no
      further augmentation of sensory neurotransmission. 6. SNP (100 nM), a nitric
      oxide donor, attenuated sensory neurogenic relaxations to EFS. 7. In rat isolated
      thoracic aortic rings, L-NAME (100 microM) and 7-NI (100 microM) attenuated
      concentration-dependent relaxations to acetylcholine. 8. These data show that NO
      modulates sensory neurotransmission evoked by EFS of the rat isolated mesenteric
      arterial bed, and that when NO synthesis is blocked sensory neurogenic relaxation
      is augmented. The source of NO is the vascular endothelium.

PMID- 12183329
TI  - Characterization of the anandamide induced depolarization of guinea-pig isolated
      vagus nerve.
AB  - 1. There is considerable interest in elucidating potential endogenously derived
      agonists of the vanilloid receptor and the role of anandamide in this regard has
      received considerable attention. In the present study, we have used an
      electrophysiological technique to investigate the mechanism of activation of
      vanilloid receptors in an isolated vagal preparation. 2. Both capsaicin and
      anandamide depolarized de-sheathed whole vagal nerve preparations that was
      antagonized by the VR1 antagonist, capsazepine (P<0.05) whilst this response was
      unaltered by the cannabinoid (CB1) selective antagonist SR141716A or the CB2
      selective antagonist, SR144528, thereby ruling out a role for cannabinoid
      receptors in this response. 3. The PKC activator, phorbol-12-myristate-13-acetate
      (PMA) augmented depolarization to both anandamide and capsaicin and this response
      was significantly inhibited with the PKC inhibitor, bisindolylmaleimide (BIM)
      (P<0.05). 4. The role of lipoxygenase products in the depolarization to
      anandamide was investigated in the presence of the lipoxygenase inhibitor, 5,8,11
      Eicosatriynoic acid (ETI). Depolarization to anandamide and arachidonic acid was
      significantly inhibited in the presence of ET1 (P<0.05). However, in the absence
      of calcium depolarization to anandamide was not inhibited by ETI. 5. Using
      confocal microscopy we have demonstrated the presence of vanilloid receptors on
      both neuropeptide containing nerves and nerves that did not stain for sensory
      neuropeptides. 6. These results demonstrate that anandamide evokes depolarization
      of guinea-pig vagus nerve, following activation of vanilloid receptors, a
      component of which involves the generation of lipoxygenase products. Furthermore,
      these receptors are distributed in both neuropeptide and non-neuropeptide
      containing nerves.

PMID- 12183330
TI  - Comparative pharmacology of rat and human alpha7 nAChR conducted with net charge
      analysis.
AB  - 1. Pharmacological studies of alpha7 nicotinic acetylcholine receptors are
      confounded by the fact that rapid desensitization to high agonist concentration
      causes alpha7 peak responses to occur well in advance of complete solution
      exchange. For this reason, peak currents are an invalid measure of response to
      applied agonist concentrations. We show that results comparable to those that
      have been corrected for instantaneous concentration are obtained if net charge is
      used as the measure of receptor response. 2. Dose response curves obtained with
      these methods indicate that alpha7 receptors are approximately 10 fold more
      sensitive to agonist than previously reported. The agonists, ACh, choline,
      cytisine, GTS-21, 4OH-GTS-21 and 4-MeO-CA have the same rank order potency for
      both human and rat receptors: 4-MeO-CA > 4OH-GTS-21 > GTS-21 > cytisine > ACh >
      choline. However, differences in efficacy exist between rat and human receptors.
      GTS-21 is more efficacious for rat than human alpha7 receptors and cytosine more
      efficacious for human than rat alpha7 receptors. 3. Choline is the least potent
      agonist for both human and rat alpha7, with a potency approximately 10 fold lower
      than that of ACh. While the EC50 for the activation of alpha7 receptors by
      choline (400-500 microM) is outside the normal physiological range (10-100
      microM), choline can nonetheless produce detectable levels of channel activation
      in the physiological concentration range. Since these concentrations are
      relatively non-desensitizing, the contribution of choline-activated alpha7
      receptor current may play a significant role in the regulation of calcium
      homeostasis in alpha7-expressing neurons.

PMID- 12183331
TI  - Nitric oxide synthase inhibitors can antagonize neurogenic and calcitonin gene
      related peptide induced dilation of dural meningeal vessels.
AB  - 1. The detailed pathophysiology of migraine is beginning to be understood and is
      likely to involve activation of trigeminovascular afferents. 2. Clinically
      effective anti-migraine compounds are believed to have actions that include
      peripheral inhibition of calcitonin gene-related peptide (CGRP) release from
      trigeminal neurones, or preventing dural vessel dilation, or both. CGRP
      antagonists can block both neurogenic and CGRP-induced dural vessel dilation. 3.
      Nitric oxide (NO) can induce headache in migraine patients and often triggers a
      delayed migraine. The initial headache is thought to be caused via a direct
      action of the NO-cGMP pathway that causes vasodilation by vascular smooth muscle
      relaxation, while the delayed headache is likely to be a result of triggering
      trigeminovascular activation. Nitric oxide synthase (NOS) inhibitors are
      effective in the treatment of acute migraine. 4. The present studies used
      intravital microscopy to examine the effects of specific NOS inhibitors on
      neurogenic dural vasodilation (NDV) and CGRP-induced dilation. 5. The non
      specific and neuronal NOS (nNOS) inhibitors were able to partially inhibit NDV,
      while the non-specific and endothelial NOS (eNOS) inhibitors were able to
      partially inhibit the CGRP induced dilation. 6. There was no effect of the
      inducible NOS (iNOS) inhibitor. 7. The data suggest that the delayed headache
      response triggered by NO donors in humans may be due, in part, to increased nNOS
      activity in the trigeminal system that causes CGRP release and dural vessel
      dilation. 8. Further, eNOS activity in the endothelium causes NO production and
      smooth muscle relaxation by direct activation of the NO-cGMP pathway, and may be
      involved in the initial headache response.

PMID- 12183332
TI  - Endothelin-1-induced venous contraction is maintained in DOCA-salt hypertension;
      studies with receptor agonists.
AB  - 1. Deoxycorticosterone acetate (DOCA) salt hypertension is associated with an
      endothelin-1 (ET-1)-dependent increase in arterial resistance and mean
      circulatory filling pressure. Contraction of endothelium-intact arteries and
      veins from sham and DOCA-salt hypertensive rats to agonists of the ET(A) (ET-1((1
      31))) and ET(B) receptor (sarafotoxin 6c; S6c) was investigated in tissue baths
      as was expression of mRNA for ET-1 and mRNA and protein for the ET(A) and ET(B)
      receptor. 2. ET-1((1-31)) contracted aorta and vena cava from sham rats with a 30
      fold lower potency than ET-1. Contraction was not altered by the ET(B) receptor
      antagonist BQ788 (100 nM) but was abolished by the ET(A) receptor antagonist ABT
      627 (30 nM). 3. In DOCA-salt thoracic aorta, maximum contraction to ET-1 and ET
      1((1-31)) was reduced (36.6 +/- 6.3 and 13.3 +/- 4.4% of sham response,
      respectively); aorta did not contract to S6c. 4. In vena cava from DOCA-salt
      rats, contraction to ET-1 and ET-1((1-31)) was not reduced compared to sham
      contraction; vena cava from sham and DOCA-salt rats contracted to S6c with a
      similar potency. 5. Real time RT-PCR revealed that prepro ET-1 mRNA was increased
      6.6 +/- 3.3 fold and 8.7 +/- 3.9 fold greater in DOCA-salt aorta and vena cava,
      respectively, compared to sham. Vena cava expressed a higher content of ET(A) and
      ET(B) receptor mRNA than aorta (P < 0.05), but no differences were observed
      between sham and DOCA-salt tissues. ET(A) and ET(B) receptor protein was
      identified in all tissues. Immunoreactive ET(A) receptor, observed as a 65, 30
      and 28 kDa bands, was expressed 400% greater in DOCA-salt aorta compared to sham,
      but was not altered in vena cava. Immunoreactive ET(B) receptor, observed as 120,
      45 and 30 kDa bands, tended to be higher in vena cava compared to aorta, but was
      not different in sham and DOCA-salt vena cava. 6. These results suggest that
      ET(A) receptor function is impaired in aorta but not vena cava of DOCA-salt rats.
      The ET(B) receptor was present in the aorta but, unlike in veins, does not
      mediate contraction directly. A sustained response to ET-1 in the venous
      circulation may contribute to the elevated blood pressure in the DOCA-salt model.

PMID- 12183333
TI  - A comparison of the actions of BIBN4096BS and CGRP(8-37) on CGRP and
      adrenomedullin receptors expressed on SK-N-MC, L6, Col 29 and Rat 2 cells.
AB  - 1. The ability of the CGRP antagonist BIBN4096BS to antagonize CGRP and
      adrenomedullin has been investigated on cell lines endogenously expressing
      receptors of known composition. 2. On human SK-N-MC cells (expressing human
      calcitonin receptor-like receptor (CRLR) and receptor activity modifying protein
      1 (RAMP1)), BIBN4096BS had a pA(2) of 9.95 although the slope of the Schild plot
      (1.37 +/- 0.16) was significantly greater than 1. 3. On rat L6 cells (expressing
      rat CRLR and RAMP1), BIBN4096BS had a pA(2) of 9.25 and a Schild slope of 0.89 +/
      0.05, significantly less than 1. 4. On human Colony (Col) 29 cells, CGRP(8-37)
      had a significantly lower pA(2) than on SK-N-MC cells (7.34 +/- 0.19 (n = 7)
      compared to 8.35 +/- 0.18, (n = 6)). BIBN4096BS had a pA(2) of 9.98 and a Schild
      plot slope of 0.86 +/- 0.19 that was not significantly different from 1. At
      concentrations in excess of 3 nM, it was less potent on Col 29 cells than on SK-N
      MC cells. 5. On Rat 2 cells, expressing rat CRLR and RAMP2, BIBN4096BS was unable
      to antagonize adrenomedullin at concentrations up to 10 microM. CGRP(8-37) had a
      pA(2) of 6.72 against adrenomedullin. 6. BIBN4096BS shows selectivity for the
      human CRLR/RAMP1 combination compared to the rat counterpart. It can discriminate
      between the CRLR/RAMP1 receptor expressed on SK-N-MC cells and the CGRP
      responsive receptor expressed by the Col 29 cells used in this study. Its slow
      kinetics may explain its apparent 'non-competitive' behaviour. At concentrations
      of up to 10 micro M, it has no antagonist actions at the adrenomedullin,
      CRLR/RAMP2 receptor, unlike CGRP(8-37).

PMID- 12183335
TI  - Characterization of two novel forms of the rat sulphonylurea receptor SUR1A2 and
      SUR1BDelta31.
AB  - 1. The ATP-sensitive potassium channel (K(ATP)) of pancreatic beta-cells is
      composed of the sulphonylurea-binding protein, SUR1, and the inwardly rectifying
      K(+) channel subunit, Kir6.2. We have characterized two novel isoforms of rat
      SUR1 in the RINm5F insulin-secreting cell line. 2. SUR1A2 is an allelic variant
      with a single amino acid change in the first nucleotide-binding domain.
      Coinjection of SUR1A2 plus Kir6.2 into Xenopus oocytes or expression of a SUR1A2
      Kir6.2 tandem in HEK-293 cells yielded large currents with characteristics
      similar to the wild-type K(ATP) channel. 3. SUR1BDelta31, detected in several
      human tissues, is a splice variant of the rat SUR1 gene that lacks exon 31 of the
      corresponding human SUR1 gene. SUR1BDelta31 lacks the TM16-TM17 transmembrane
      spanning helices leading to a protein with a different transmembrane topology.
      Coinjection of SUR1BDelta31 plus Kir6.2 into Xenopus oocytes or expression of the
      Kir6.2/SUR1BDelta31 tandem construct in HEK-293 cells did not result in any
      current, and a surface expression assay indicated that this channel does not
      reach the plasma membrane. 4. SUR1A2 and SUR1A1 proteins expressed in HEK-293
      cells display similar binding affinities for [(3)H]-glibenclamide, while
      SUR1BDelta31 shows a 500-fold lower affinity. 5. These findings confirm that TM16
      TM17 of SUR1 are important for high-affinity glibenclamide binding and that their
      deletion impairs trafficking of the K(ATP) channel to the surface membrane.

PMID- 12183334
TI  - Rapid neuromodulation by cortisol in the rat paraventricular nucleus: an in vitro
      study.
AB  - 1. We have used a range of in vitro electrophysiological techniques to
      investigate the mechanism of rapid cortisol neuromodulation of parvocellular
      neurones in the rat paraventricular nucleus. 2. In our study, we found that
      cortisol (10 microM) increased spontaneous action-current firing frequency to
      193%. This effect was insensitive to the glucocorticoid intracellular-receptor
      antagonist mifepristone. 3. Cortisol (0.1-10 microM) had no detectable effects on
      whole-cell GABA current amplitudes, or GABA(A) single-channel kinetics. 4.
      Cortisol (10 microM) inhibited whole-cell potassium currents in parvocellular
      neurones by shifting the steady-state activation curve by 14 mV to the right. 5.
      Additionally, in a cell line expressing both the glucocorticoid intracellular
      receptor and recombinant, fast inactivating potassium channels (hKv1.3), cortisol
      (1 and 10 microM) inhibited potassium currents by shifting their steady-state
      activation curves to the right by 12 mV (10 microM cortisol). This effect was
      also insensitive to the cortisol antagonist, mifepristone. 6. These data suggest
      that inhibition of voltage-gated potassium channels may contribute to the rapid
      neuromodulatory effects of cortisol, possibly by direct interaction with the ion
      channel itself.

PMID- 12183337
TI  - Protein kinase mediated upregulation of endothelin A, endothelin B and 5
      hydroxytryptamine 1B/1D receptors during organ culture in rat basilar artery.
AB  - 1. Organ culture has been shown to upregulate both endothelin (ET) and 5
      hydroxytryptamine 1B/1D (5-HT(1B/1D)) receptors in rat cerebral arteries. The
      purpose of the present study was to investigate the involvement of protein
      kinases, especially protein kinases C (PKC) and A (PKA) in this process. 2. The
      effect of inhibiting protein kinases during organ culture with staurosporine
      (unspecific protein kinase inhibitor), RO 31-7549 (specific inhibitor of
      classical PKC's) and H 89 (specific inhibitor of PKA) was examined using in vitro
      pharmacological examination of cultured vessel segments with ET-1 (unspecific
      ET(A) and ET(B) agonist), S6c (specific ET(B) agonist) and 5-CT (5-HT(1)
      agonist). Levels of mRNA coding for the ET(A), ET(B), 5-HT(1B) and 5-HT(1D)
      receptors were analysed using real-time RT-PCR. 3. Classical PKC's are critically
      involved in the appearance of the ET(B) receptor; co-culture with RO 31-7549
      abolished the contractile response (6.9 +/- 1.8%) and reduced the ET(B) receptor
      mRNA by 44 +/- 4% as compared to the cultured control. Correlation between
      decreased ET(B) receptor mRNA and abolished contractile function indicates
      upstream involvement of PKC. 4. Inhibition of PKA generally had an enhancing
      effect on the induced changes giving rise to a 7-25% increase in E(max) in
      response to ET-1, S6c and 5-CT as compared to the cultured control. 5.
      Staurosporine inhibited the culture induced upregulation of the response of both
      the ET(A) and the 5-HT(1B/1D) receptors, but had no significant effect on the
      mRNA levels of these receptors. This lack of correlation indicates an additional
      downstream involvement of protein kinases.

PMID- 12183336
TI  - Distinct roles of GPVI and integrin alpha(2)beta(1) in platelet shape change and
      aggregation induced by different collagens.
AB  - 1. Various platelet membrane glycoproteins have been proposed as receptors for
      collagen, in some cases as receptors for specific collagen types. In this study
      we have compared the ability of a range of collagen types to activate platelets.
      2. Bovine collagen types I-V, native equine tendon collagen fibrils and collagen
      related peptide (CRP) all induced platelet aggregation and shape change. 3.
      Responses were abolished in FcRgamma chain-deficient platelets, which also lack
      GPVI, indicating a critical dependence on the GPVI/FcRgamma chain complex. 4.
      Responses to all collagens were unaffected in CD36-deficient platelets. 5. A
      monoclonal antibody (6F1) which binds to the alpha(2) integrin subunit of human
      platelets had a minimal effect on the rate and extent of aggregation induced by
      the collagens; however, it delayed the onset of aggregation following addition of
      all collagens. For shape change, 6F1 abolished the response induced by collagen
      types I and IV, substantially attenuated that to collagen types II, III and V,
      but only partially inhibited Horm collagen. 6. Simultaneous blockade of the
      P2Y(1) and P2Y(12) receptors, and inhibition of cyclo-oxygenase demonstrated that
      CRP can activate platelets independently of ADP and TxA(2); however, responses to
      the collagens were dependent on these mediators. 7. This study confirms the
      importance of the GPVI/FcRgamma chain complex in platelet responses induced by a
      range of collagen agonists, while providing no evidence for collagen type
      specific receptors. It also provides evidence for a modulatory role of
      alpha(2)beta(1), the significance of which depends on the collagen preparation.

PMID- 12183339
TI  - Childhood seizures and their consequences for the hippocampus.

PMID- 12183338
TI  - Potentiation of slow component of delayed rectifier K(+) current by cGMP via two
      distinct mechanisms: inhibition of phosphodiesterase 3 and activation of protein
      kinase G.
AB  - 1. Regulation of the slowly activating component of delayed rectifier K(+)
      current (I(Ks)) by intracellular guanosine 3'5' cyclic monophosphate (cGMP) was
      investigated in guinea-pig sino-atrial (SA) node cells using the whole-cell patch
      clamp method. 2. When a cell was dialyzed with pipette solution containing 100
      micro M cGMP, I(Ks) started to gradually increase and reached a maximum increase
      of a factor of 2.37 +/- 0.39 (n = 4) about 10-15 min after rupture of patch
      membrane. Atrial natriuretic peptide (ANP, 100 nM) also potentiated I(Ks),
      consistent with intracellular cGMP-induced enhancement of I(Ks). 3. Bath
      application of a selective blocker of the cGMP-inhibited phosphodiesterase (PDE3)
      milrinone (100 microM) enhanced I(Ks) by a factor of 1.50 +/- 0.09 (n = 4) but
      failed to further enhance I(Ks) after a maximum stimulation by intracellular cGMP
      (100 microM), suggesting that blockade of PDE3 activity is involved in the
      enhancement of I(Ks). A potent but nonspecific PDE inhibitor 3-isobutyl-1
      methylxanthine (IBMX, 100 microM) further increased I(Ks) stimulated by 100
      microM milrinone, indicating that PDE subtypes other than PDE3 are also involved
      in the regulation of basal I(Ks) in guinea-pig SA node cells. 4. Bath application
      of 100 microM 8-bromoguanosine 3'5' cyclic monophosphate (8-Br-cGMP) increased
      I(Ks) by a factor of 1.48 +/- 0.11 (n = 5) and this stimulatory effect was
      totally abolished by cGMP-dependent protein kinase (PKG) inhibitor KT-5823 (500
      nM), suggesting that the activation of PKG also mediates cGMP-induced
      potentiation of I(Ks). 5. These results strongly suggest that intracellular cGMP
      potentiates I(Ks) not only by blocking PDE3 but also by activating PKG in guinea
      pig SA node cells.

PMID- 12183340
TI  - Disease modification in partial epilepsy.
AB  - With the growth in antiepileptic drug treatment, the question arises as to what
      extent we are merely treating the symptom (i.e. the seizures) rather than the
      underlying disease process (i.e. epileptogenesis). Epileptogenicity can be
      considered as the process whereby structural and functional changes occur
      following an insult that in some cases result in epilepsy. Epileptogenicity also
      describes some of the changes and processes that contribute to the progression
      observed in some epilepsies. These processes have been modelled in animals mostly
      by the kindling model of epilepsy, in which repetition of subconvulsive stimuli
      results in a progressive epileptic state and eventually leads to spontaneous
      seizures. However, it is not clear that kindling has a human correlate, so models
      in which an initial insult (status epilepticus, hyperthermia, hypoxia, trauma) is
      followed by the development of lowered seizure threshold and, in some instances,
      spontaneous seizures have been used. These models seem to support the "second
      hit" hypothesis, in which there is an initial insult resulting in lowered seizure
      threshold, and then a later insult, the "second hit", that results in the
      expression of epilepsy. These models also support the concept of a latent period
      during which there could be targeted therapies to prevent the epileptogenic
      process. Although the occurrence of neuronal damage is one such target, neuronal
      damage is not necessary for epileptogenesis, and other mechanisms are at play. At
      the present time, it is not known whether targeted therapies may also affect
      compensatory processes, such as brain repair. Clearly, this would be a potential
      risk of such strategies. Epidemiological evidence and trials indicate that our
      present antiepileptic drugs are not effective in preventing epileptogenesis;
      antiepileptic drugs were, however, not designed for this purpose. Data from
      animal experiments suggest that treatment of non-convulsive status epilepticus
      following specific insults may prevent epileptogenesis. The relevance of this for
      the human condition remains uncertain, but non-convulsive status epilepticus is
      probably an under-recognized and probably under-treated condition. Perhaps one of
      the most salutary findings has been the observation of decreased childhood
      epilepsy with improved neonatal care. This highlights the importance of medical
      care at the time of an insult, and of prevention of the insults. This review
      discusses the data that support the concepts underlying epileptogenesis and the
      model systems that are presumed to reflect the human condition. Particular
      attention is paid to the potential for interrupting the processes underlying
      epileptogenesis.

PMID- 12183341
TI  - Magnetic resonance imaging findings within 5 days of status epilepticus in
      childhood.
AB  - The nature of the relationships between status epilepticus, acute hippocampal
      injury, mesial temporal sclerosis (MTS) and temporal lobe epilepsy remains
      unclear. The aim of this study was to investigate whether generalized status
      epilepticus is associated with brain abnormalities, especially in the mesial
      temporal lobe, within 5 days of the acute event. Such changes may be the first
      part of a causative pathophysiological sequence relating status epilepticus and
      MTS. Thirty-five children with a history of status epilepticus, including 21 with
      a history of prolonged febrile convulsion (PFC), underwent qualitative and
      quantitative MRI investigations within 5 days of the acute episode. Quantitative
      assessments of the hippocampus included T(2) relaxometry and hippocampal
      volumetry. Hippocampal volumes were large in patients with PFC when compared with
      controls. In addition, T(2) relaxation time was elevated in patients with PFC
      compared with control subjects during the first 2 days of the acute event. No
      difference was observed in patients examined 3-5 days after the event. Patients
      with afebrile status epilepticus had a variety of imaging abnormalities including
      elevated hippocampal T(2) values, but no evidence of hippocampal enlargement. PFC
      is associated with hippocampal abnormalities, consistent with hippocampal oedema,
      whilst non-febrile status epilepticus is not. A systematic longitudinal study is
      required to characterize the evolution of these abnormalities and to determine
      whether any patient develops MTS.

PMID- 12183342
TI  - Ictal cerebral haemodynamics of childhood epilepsy measured with near-infrared
      spectrophotometry.
AB  - Near-infrared spectrophotometry (NIRS) is a new technique that allows continuous
      non-invasive monitoring of tissue oxygenation and haemodynamics in the brain. We
      used NIRS in various types of paediatric epileptic seizures in order to
      understand the pathophysiology of epileptic seizures in childhood epilepsy. This
      study examined 15 children ranging in age from 1.5 months to 16 years (nine males
      and six females), with different types of epilepsy. Six series of tonic spasms
      and 67 isolated seizures were recorded. The results demonstrated that several
      pathophysiological processes exist during epileptic seizures in childhood. (i)
      Convulsive seizures were associated with a remarkable increase in cerebral blood
      volume (CBV), while absence seizures were associated with a mild decrease or no
      change in CBV of the frontal cortex. (ii) An initial transient decrease in CBV
      was observed in some types of convulsive seizures. (iii) An ictal increase in CBV
      changed to an ictal decrease in the course of tonic status epilepticus. (iv)
      There was definite heterogeneity in the CBV changes during tonic spasms in
      patients with West syndrome. NIRS is easily applicable to paediatric patients
      with epilepsy and may provide new insights into the pathophysiology of various
      types of epileptic seizure.

PMID- 12183343
TI  - Re-expression of PSA-NCAM by demyelinated axons: an inhibitor of remyelination in
      multiple sclerosis?
AB  - Multiple sclerosis is affecting approximately 1 out of every 1000 individuals in
      the western world. After axons are denuded of myelin in the early stages of the
      disease, remyelination occurs, but eventually this process fails, and permanent
      disability is the result. During development, the polysialylated form of the
      neural cell adhesion molecule NCAM, PSA-NCAM, is expressed at the axonal surface
      and acts as a negative regulator of myelination, presumably by preventing myelin
      forming cells from attaching to the axon. Removal of PSA-NCAM from the axonal
      surface is a prerequisite for the initiation of myelination. We questioned
      whether, in multiple sclerosis, re-expression of PSA-NCAM by axons could occur,
      and therefore account for the failure of remyelination. Forty multiple sclerosis
      lesions from 24 different post-mortem multiple sclerosis cases were selected by
      histological methods and analysed by immunohistochemistry. Demyelinated lesions
      and partially remyelinated lesions (shadow plaques) were studied. Controls
      consisted of post-mortem brain tissue from patients with amyotrophic lateral
      sclerosis and without neurological disease. We showed that PSA-NCAM, normally
      absent from adult brain, is re-expressed on demyelinated axons in the plaques.
      Within shadow plaques, remyelinated axons do not express PSA-NCAM. Re-expression
      of PSA-NCAM could act as an inhibitor of remyelination and participate in disease
      progression in multiple sclerosis.

PMID- 12183344
TI  - Response slowing in Parkinson's disease: a psychophysiological analysis of
      premotor and motor processes.
AB  - The mechanisms responsible for reaction time slowing in Parkinson's disease were
      investigated using movement-related potentials in a choice reaction time task.
      Parkinson's disease patients and control subjects were required to respond with
      the left or right hand to indicate whether a visual stimulus was relatively large
      or small. The difficulty of the size discrimination was manipulated, as was the
      complexity of the manual response (single key press versus sequence of three key
      presses). Behavioural responses of Parkinson's disease patients were slower than
      those of control subjects, especially when complex responses were required.
      Moreover, the timing of movement-related potentials indicated that motor
      processes clearly required extra time, relative to control subjects, for
      Parkinson's disease patients making complex responses. In addition, delayed onset
      of the movement-related potentials indicated that one or more premotor processes
      are also slowed in these patients.

PMID- 12183345
TI  - Subthalamic nucleus stimulation affects striato-anterior cingulate cortex circuit
      in a response conflict task: a PET study.
AB  - The subthalamic nucleus (STN) has generally been considered as a relay station
      within frontal-subcortical motor control circuitry. Little is known about the
      influence of the STN on cognitive networks. Clinical observations and studies in
      animals suggest that the STN participates in non-motor functions which can now be
      probed in Parkinson's disease patients with deep brain stimulation of the STN,
      allowing selective and reversible modulation of this nucleus. Using PET, we
      studied changes in regional cerebral blood flow (rCBF) associated with a response
      conflict task (Stroop task) in Parkinson's disease patients ON and OFF bilateral
      STN stimulation. The Stroop task requires subjects to name the font colour of
      colour words (e.g. "blue") printed in an incongruent colour ink (e.g. yellow).
      During STN stimulation, impaired task performance (prolonged reaction times) was
      associated with decreased activation in both right anterior cingulate cortex
      (ACC) and right ventral striatum. Concomitant increased activation in left
      angular gyrus indicative of ongoing word processing during stimulation is
      consistent with an impairment to inhibit habitual responses. ACC and ventral
      striatum are part of the ACC circuit associated with response conflict tasks. The
      decreased activation during STN stimulation in the ACC circuit, while response
      conflict processing worsened, provides direct evidence of STN modulating non
      motor basal ganglia-thalamocortical circuitry. Impairment in ACC circuit function
      could account for the subtle negative effects on cognition induced by STN
      stimulation.

PMID- 12183346
TI  - Suppression of eye movements improves balance.
AB  - The aim of this study was to investigate the possible interaction of vestibulo
      ocular and vestibulo-spinal functions. Spontaneous eye movements and anterior
      posterior and lateral body sway were recorded simultaneously in 10 patients with
      vestibular neuritis (Experiment 1) and in 11 healthy subjects (Experiment 2)
      while all subjects wore a mask that allowed fixation of a head-fixed target. For
      the healthy subjects, there was no significant difference in postural sway for
      the conditions of eyes open in darkness and fixation of the head-fixed target.
      For the patients, the question was whether transient suppression of the
      spontaneous nystagmus by fixating the target affected excessive body sway or
      whether modulation of nystagmus and postural sway were largely independent. The
      mean peak slow-phase velocity of the spontaneous nystagmus decreased from 13.5 +/
      5.6 to 4.3 +/- 2.4 degrees /s during fixation. The suppression of nystagmus also
      reduced postural sway while standing on foam rubber. Mean value decreased from
      25.2 +/- 7.6 to 16.2 +/- 7.7 mm (right-left root mean square values; ANOVA, P =
      0.003). Since a head-fixed target was used to suppress spontaneous eye movements,
      the data cannot be explained by any stabilizing effect of afferent visual cues.
      Instead, ocular motor efference copy signals or reafferences may have contributed
      to the postural instability of patients with vestibular neuritis, which would
      explain the reduction of postural sway during fixation suppression of the
      nystagmus. Thus, ocular motor signals rather than afferent visual cues about
      retinal slip are used for visual control of postural sway, at least in this
      experimental paradigm.

PMID- 12183347
TI  - Spatial neglect in near and far space investigated by repetitive transcranial
      magnetic stimulation.
AB  - Localized repetitive transcranial magnetic stimulation was used to disrupt
      visuospatial perception in the near and far space of six healthy volunteer
      subjects. In addition to the baseline condition, they were stimulated over the
      right posterior parietal cortex, the right or left dorsal occipital cortex or the
      right ventral occipital cortex, during the brief presentation of a transected
      horizontal line. Subjects had to indicate whether the part of the line to the
      left or right of the transection appeared longer. The stimulus display was back
      projected on a screen at a viewing distance of either 50 or 150 cm ("near" and
      "far" space, respectively). Reaction times and choices were measured. In a forced
      choice paradigm, subjects showed "pseudoneglect", the natural tendency of
      neurologically intact subjects to perceive the left side of a centrally
      transected line as slightly longer than the right. These errors occurred more for
      lines in near space than for lines in far space. Magnetic stimulation of the
      right posterior parietal cortex or the right ventral occipital lobe selectively
      induced a significant shift to the right in the perceived midpoint for near- and
      far-space lines, respectively. The results reproduced in normal subjects the
      dissociation between neglect in near and far space that has been described in
      patients with different right-hemisphere lesions. This dissociation supports the
      contention that there is a dorsal/near space-ventral/far space segregation of
      processing in the visual system which reflects the behavioural goals of the two
      putative visual streams.

PMID- 12183348
TI  - Effects of monocular viewing and eye dominance on spatial attention.
AB  - Observations in primates and patients with unilateral spatial neglect have
      suggested that patching of the eye ipsilateral to the injury and contralateral to
      the neglected space can sometimes improve attention to the neglected space.
      Investigators have generally attributed the effects of monocular eye patching to
      activation of subcortical centers that interact with cortical attentional
      systems. Eye patching is thought to produce preferential activation of
      attentional systems contralateral to the viewing eye. In this study we examined
      the effect of monocular eye patching on attentional biases in normal subjects.
      When normal subjects bisect vertical (radial) lines using both eyes, they
      demonstrate a far attentional bias, misbisecting lines away from their body. In a
      monocular viewing experiment, we found that the majority of subjects, who were
      right eye dominant, had relatively nearer bisections and a diminished far bias
      when they used their right eye (left eye covered) compared with when they used
      their left eye (right eye covered). The smaller group of subjects who were left
      eye dominant had relatively nearer bisections and a diminished far bias when they
      used their left eye compared with when they used their right eye. In the
      hemispatial placement experiment, we directly manipulated hemispheric engagement
      by having subjects perform the same task in right and left hemispace. We found
      that right eye dominant subjects had a diminished far bias in right hemispace
      relative to left hemispace. Left eye dominant subjects showed the opposite
      pattern and had a diminished far bias in left hemispace. For both groups, spatial
      presentation affected performance more for the non-dominant eye. The results
      suggest that monocular viewing is associated with preferential activation of
      attentional systems in the contralateral hemisphere, and that the right
      hemisphere (at least in right eye dominant subjects) is biased towards far space.
      Finally, the results suggest that the poorly understood phenomenon of eye
      dominance may be related to hemispheric specialization for visual attention.

PMID- 12183349
TI  - Abeta 17-42 in Alzheimer's disease activates JNK and caspase-8 leading to
      neuronal apoptosis.
AB  - The p3 peptide [amyloid beta-peptide (Abeta) 17-40/42], derived by alpha- and
      gamma-secretase cleavage of the amyloid precursor protein (APP), is a major
      constituent of diffuse plaques in Alzheimer's disease and cerebellar pre-amyloid
      in Down's syndrome. However, the importance of p3 peptide accumulation in
      Alzheimer's disease and its toxic properties is not clear. Here, we demonstrate
      that treatment of cells with Abeta 17-42 leads to apoptosis in two human
      neuroblastoma cell lines, SH-SY5Y and IMR-32. Abeta 17-42 activated caspase-8 and
      caspase-3, induced poly(ADP-ribose) polymerase cleavage, but did not activate
      caspase-9. Selective caspase-8 and caspase-3 inhibitors completely blocked Abeta
      17-42-induced neuronal death. Abeta 17-42 moderately activated c-Jun N-terminal
      kinase (JNK); however, overexpression of a dominant-negative mutant of SEK1, the
      upstream kinase of JNK, protected against Abeta 17-42 induced neuronal death.
      These results demonstrate that Abeta 17-42 induced neuronal apoptosis via a Fas
      like/caspase-8 activation pathway. Our findings reveal the previously
      unrecognized toxic effect of Abeta 17-42. We propose that Abeta 17-42 constitutes
      an additional toxic peptide derived from APP proteolysis and may thus contribute
      to the neuronal cell loss characteristic of Alzheimer's disease.

PMID- 12183350
TI  - The dynamic time course of semantic memory impairment in Alzheimer's disease:
      clues from hyperpriming and hypopriming effects.
AB  - The nature of semantic memory deficit in Alzheimer's disease is still a matter of
      controversy. To clarify this issue, we examined the evolution of semantic memory
      impairment in 24 Alzheimer's disease patients by means of a longitudinal study.
      We used two semantic tasks, one explicit and the other implicit, to evaluate the
      integrity of the same concepts. The explicit task was a semantic knowledge task
      composed of naming and questions, involving superordinate and attribute knowledge
      of concepts. The implicit task, a lexical decision task, assessed semantic
      priming and allowed a very pure measurement of semantic memory. In this task,
      related pairs of words had coordinate (e.g. "tiger-lion") or attribute ("tiger
      stripe") relationships. In the coordinate relation between two words, the
      semantic priming performances were at first paradoxical: they increased
      abnormally (hyperpriming) before falling down, whereas in the attribute
      condition, the priming effects were first normal and then started to decrease in
      the final sessions (hypopriming). Compared with the semantic knowledge
      performance, these apparently disconcerting results reflect a coherent pattern of
      semantic memory degradation in Alzheimer's disease that is a progressive
      deterioration starting with specific attribute information. The data reveal in an
      astonishing yet striking manner the dynamic semantic memory degradation in
      Alzheimer's disease through the apparently paradoxical semantic priming effects.

PMID- 12183351
TI  - Prospective randomized trial of lisuride infusion versus oral levodopa in
      patients with Parkinson's disease.
AB  - Motor complications are a major source of disability for patients with advanced
      Parkinson's disease. Surgical therapies provide benefit to some, but these
      treatments are expensive and associated with adverse effects. Current research
      indicates that motor complications are associated with abnormal, intermittent,
      pulsatile stimulation of denervated dopamine receptors using short acting
      dopaminergic agents such as levodopa. Retrospective studies suggest that the use
      of longer-acting more continuous dopaminergic therapies can improve both motor
      fluctuations and dyskinesia. We performed a prospective, long-term (4-year) trial
      comparing patients randomized to receive subcutaneous infusion of the dopamine
      agonist lisuride versus conventional therapy with oral levodopa and dopamine
      agonists. We demonstrate that patients receiving lisuride infusions experienced a
      significant reduction in both motor fluctuations and dyskinesia compared with
      patients receiving standard dopaminergic therapies. Benefits persisted for the 4
      year duration of the study. Mean Unified Parkinson's Disease Rating Scale scores
      in "ON" and "OFF" states did not significantly change between baseline and 4
      years for patients in the lisuride group, but deteriorated in patients in the
      levodopa group. This study indicates that continuous lisuride infusion can be
      beneficial for patients with advanced Parkinson's disease and reverse established
      motor fluctuations and dyskinesia.

PMID- 12183352
TI  - Can segregation within the semantic system account for category-specific
      deficits?
AB  - Functional neuroimaging was used to investigate the extent to which category
      specific semantic deficits in patients can be accounted for in terms of the
      demands placed on neural systems underlying different types of semantic
      knowledge. Unlike previous functional imaging studies of category specificity, we
      used a factorial design that crossed category (tools and fruits) with tasks
      requiring retrieval of either action or perceptual (real life size) knowledge.
      The presentation of tools relative to fruit increased activation in the same left
      posterior middle temporal area that was linked to the retrieval of action
      knowledge in general (for fruit as well as tools). However, we found no
      correlation between activation evoked by fruit and the size retrieval task. The
      left medial anterior temporal cortex was the only region to be activated for
      fruit relative to tools. We argue that the sensory-functional theory of category
      specific effects is insufficient to account for the current neuroimaging
      literature. However, the data do support a more refined version of the theory:
      tools, relative to fruit, are more strongly linked to manipulative/motor
      knowledge and, for some tasks, fruit may be more reliant on integrating multiple
      semantic features.

PMID- 12183353
TI  - Vestibular-evoked postural responses in the absence of somatosensory information.
AB  - In order to investigate the ways in which sensory channels interact to control
      balance, we measured the postural response evoked by galvanic vestibular
      stimulation (GVS) in a rare subject (I. W.) with a large-fibre sensory
      neuronopathy. I. W. has no sensations of cutaneous light touch and
      movement/position sense below the neck, and without vision he has no knowledge of
      where his limbs and body are in space. He was tested with and without vision
      while seated. With eyes closed, I. W.'s responses to pure vestibular stimuli were
      an order of magnitude larger than those of healthy controls. In other respects
      his responses were normal. Part of this phenomenon may have been due to lack of
      response modification by somatosensory feedback. However, the initial development
      of his ground reaction force, which is the earliest mechanical indicator of the
      response, differed from that of a control subject from its beginning. Similarly,
      opening his eyes resulted in a reduction (>50%) of the response from its
      beginning. We propose that these early changes reflect changes in initial
      response selection, possibly by alterations in the gain of vestibulopostural
      channels. We suggest that similar gain changes operate in healthy subjects and
      occur through a fast dynamic process. A model is put forward in which the weight
      of each sensory channel is adjusted continuously in a competitive manner
      according to the balance-relevant information content of the other sensory
      channels. As a secondary issue, the nature of I. W.'s head and trunk tilt
      response provides insight into the question of which vestibular afferents are
      recruited by GVS. I. W.'s responses consisted of an initial, relatively fast tilt
      followed by a slower, continuous tilt. When the stimulus was turned off, his body
      partially tilted back at an intermediate velocity. We modelled this behaviour as
      the algebraic sum of a position response and a constant velocity response. We
      suggest that these two components arise from stimulation of otolith and
      semicircular canal afferents, respectively.

PMID- 12183354
TI  - Altered sensorimotor integration in Parkinson's disease.
AB  - Transcranial magnetic stimulation (TMS) was used to investigate sensorimotor
      integration in the upper limb of 10 patients with Parkinson's disease and 10 age
      matched controls. Non-conditioned and subthreshold conditioned (2 ms
      interstimulus interval) responses were recorded in the flexor and extensor carpi
      radialis muscles (FCR and ECR) of the more impaired (non-dominant) limb. Stimuli
      were delivered while the wrist joint was positioned statically at various joint
      angles as well as during different phases of passive movement of the wrist joint
      (90 degrees amplitude, 0.2 Hz). The FCR and ECR muscles remained relaxed during
      all stimulation. In both groups, responses in the static condition were larger
      when the target muscle was in a shortened position. Responses were also
      facilitated in the muscle shortening phases of passive movement. In both static
      and dynamic conditions, the extent of modulations in response amplitude was
      significantly reduced in the patient group. The level of intracortical inhibition
      (ICI) was also significantly less in the Parkinson's disease patients in static
      conditions. During passive movement, control subjects demonstrated a clear
      reduction in ICI compared with the static trials; however, the level of ICI was
      unchanged in the Parkinson's disease group in the dynamic condition. The results
      suggest an abnormal influence of afference on corticomotor excitability in
      Parkinson's disease. This may be related to abnormal sensory input, a defective
      integrative unit or an inappropriate motor response.

PMID- 12183355
TI  - Postural instability in idiopathic Parkinson's disease: the role of medication
      and unilateral pallidotomy.
AB  - Postural instability (PI) is common in idiopathic Parkinson's disease (IPD). We
      measured sensory and motor contributions to PI in 50 patients with advanced IPD,
      off and on medication and in a subset pre- and 3, 6 and 12 months post-unilateral
      pallidotomy, using computerized dynamic posturography [specifically, the Sensory
      Organization Test (SOT) and the Unified Parkinson's Disease Rating Scale (UPDRS)
      subscale PIGD (Postural Instability and Gait Disorder)]. Off medication, all
      patients had abnormal PIGD scores. The group could be separated into those with
      normal SOT equilibrium scores (SOTN) and those, the majority, with abnormal
      postural control when sensory feedback was limited (SOTABN). Medication improved
      the PIGD scores but worsened the SOT scores in the majority of patients.
      Increases in spontaneous sway in some patients contributed to the negative effect
      of medication on SOT scores. However, this could not explain the detrimental
      effect of medication on SOT scores in at least 40% of patients. On the other
      hand, pallidotomy improved both PIGD and SOT scores in both groups. A predictor
      of good outcome from pallidotomy concerning PI was the degree of worsening of the
      effect that medication had on SOT5 scores. PI in IPD appears to be
      multifactorial. We propose that the PIGD score reflects sensory and motor aspects
      of postural control, with normal sensory feedback, while the SOT equilibrium
      scores measure the sensory organizational process of postural control in the
      presence of altered sensory inputs. There is a dissociation between the effects
      of medication and pallidotomy on motor and sensory components of postural
      control, which may reflect the underlying pathophysiological mechanism
      responsible for these different components of PI. We suggest that patients with
      advanced IPD and PI on medication should consider adjuvant surgical treatment for
      better postural control.

PMID- 12183356
TI  - Spinocerebellar ataxia type 3 (Machado-Joseph disease): severe destruction of the
      lateral reticular nucleus.
AB  - The lateral reticular nucleus (LRT) of the medulla oblongata is a precerebellar
      nucleus involved in proprioception and somatomotor automatisms. We investigated
      this nucleus in five individuals with clinically diagnosed and genetically
      confirmed spinocerebellar ataxia type 3 (SCA3, Machado-Joseph disease).
      Polyethylene glycol-embedded 100 micro m thick sections stained for lipofuscin
      granules and Nissl material as well as Nissl-stained paraffin-embedded sections
      revealed severe destruction of the LRT in all SCA3 brains examined. Some of the
      few surviving neurones contained ataxin-3-immunopositive intranuclear inclusion
      bodies, as noted in other affected brain regions in SCA3. Along with the severe
      neuronal depletion, obvious astrogliosis was seen in the LRT of all SCA3
      patients. The findings suggest that the LRT is a consistent target of the
      pathological process underlying SCA3. In view of its afferent and efferent
      connections, destruction of the LRT probably contributes to gait ataxia in
      individuals suffering from SCA3.

PMID- 12183357
TI  - Transmission of group II heteronymous pathways is enhanced in rigid lower limb of
      de novo patients with Parkinson's disease.
AB  - A potent heteronymous excitation of quadriceps motoneurones via common peroneal
      group II afferents has recently been demonstrated in normal subjects. The aim of
      this study was to investigate whether this group II excitation contributes to
      rigidity in Parkinson's disease. The early and late facilitations of the
      quadriceps H reflex elicited by a conditioning volley to the common peroneal
      nerve (CPN) at twice motor threshold, attributed to non-monosynaptic group I and
      group II excitations, respectively, were investigated. The comparison was drawn
      between results obtained in 20 "de novo" patients with Parkinson's disease
      (hemiparkinsonian, 17; bilateral, three) and 20 age-matched normal subjects.
      There was no statistically significant effect of "group" (patients/controls),
      "duration", "global severity" [Unified Parkinson's Disease Rating Scale (UPDRS)]
      or "side" (unilaterally versus bilaterally affected) factors on either group I or
      group II facilitations. To further the analysis, the factors of status (affected
      or non-affected limb), akinesia (lower limb akinesia score) and rigidity (lower
      limb rigidity score) were entered in a general linear model to explain the
      variations of the quadriceps H reflex facilitation. Rigidity was the only factor
      useful in predicting the value of the group II facilitation of the quadriceps H
      reflex (P < 0.007). Group I and group II facilitation was then compared between
      the rigid, non-rigid and control lower limbs [multivariate analysis of variance
      (MANOVA)]. Results are represented as mean +/- SEM (standard error of the mean).
      Group II facilitation was enhanced in the rigid lower limb of unilaterally
      affected patients (153.2 +/- 7% of control H reflex) compared with non-rigid
      lower limbs (124 +/- 4% of control H reflex; P < 0.007) or control lower limbs
      (126.1 +/- 4.1%; P < 0.01). There was no difference between the non-rigid lower
      limbs of the unilaterally affected patients and the control lower limbs, but a
      difference was observed between the rigid lower limbs of unilaterally less
      affected and bilaterally more affected patients (153.2 +/- 7% and 123.8 +/- 7.5%
      of control H reflex, respectively; P < 0.04). These results suggest a
      facilitation of the transmission in the interneuronal pathway activated by group
      II afferents in rigid lower limb of de novo hemiparkinsonian patients, probably
      resulting from a change in their descending monoaminergic inhibitory control.

PMID- 12183358
TI  - The RASputin effect.

PMID- 12183359
TI  - Wild chromatin: regulation of eukaryotic genes in their natural chromatin
      context.

PMID- 12183360
TI  - Distinct requirements for Ras oncogenesis in human versus mouse cells.
AB  - The spectrum of tumors associated with oncogenic Ras in humans often differs from
      those in mice either treated with carcinogens or engineered to sporadically
      express oncogenic Ras, suggesting that the mechanism of Ras transformation may be
      different in humans. Ras stimulates primarily three main classes of effector
      proteins, Rafs, PI3-kinase, and RalGEFs, with Raf generally being the most potent
      at transforming murine cells. Using oncogenic Ras mutants that activate single
      effectors as well as constitutively active effectors, we find that the RalGEF,
      and not the Raf or PI3-kinase pathway, is sufficient for Ras transformation in
      human cells. Thus, oncogenic Ras may transform murine and human cells by distinct
      mechanisms, and the RalGEF pathway--previously deemed to play a secondary role in
      Ras transformation--could represent a new target for anti-cancer therapy.

PMID- 12183361
TI  - Nr-CAM is a target gene of the beta-catenin/LEF-1 pathway in melanoma and colon
      cancer and its expression enhances motility and confers tumorigenesis.
AB  - beta-catenin and plakoglobin (gamma-catenin) are homologous molecules involved in
      cell adhesion, linking cadherin receptors to the cytoskeleton. beta-catenin is
      also a key component of the Wnt pathway by being a coactivator of LEF/TCF
      transcription factors. To identify novel target genes induced by beta-catenin
      and/or plakoglobin, DNA microarray analysis was carried out with RNA from cells
      overexpressing either protein. This analysis revealed that Nr-CAM is the gene
      most extensively induced by both catenins. Overexpression of either beta-catenin
      or plakoglobin induced Nr-CAM in a variety of cell types and the LEF/TCF binding
      sites in the Nr-CAM promoter were required for its activation by catenins.
      Retroviral transduction of Nr-CAM into NIH3T3 cells stimulated cell growth,
      enhanced motility, induced transformation, and produced rapidly growing tumors in
      nude mice. Nr-CAM and LEF-1 expression was elevated in human colon cancer tissue
      and cell lines and in human malignant melanoma cell lines but not in melanocytes
      or normal colon tissue. Dominant negative LEF-1 decreased Nr-CAM expression and
      antibodies to Nr-CAM inhibited the motility of B16 melanoma cells. The results
      indicate that induction of Nr-CAM transcription by beta-catenin or plakoglobin
      plays a role in melanoma and colon cancer tumorigenesis, probably by promoting
      cell growth and motility.

PMID- 12183362
TI  - The ankyrin repeat protein Diversin recruits Casein kinase Iepsilon to the beta
      catenin degradation complex and acts in both canonical Wnt and Wnt/JNK signaling.
AB  - Wnt signals control decisive steps in development and can induce the formation of
      tumors. Canonical Wnt signals control the formation of the embryonic axis, and
      are mediated by stabilization and interaction of beta-catenin with Lef/Tcf
      transcription factors. An alternative branch of the Wnt pathway uses JNK to
      establish planar cell polarity in Drosophila and gastrulation movements in
      vertebrates. We describe here the vertebrate protein Diversin that interacts with
      two components of the canonical Wnt pathway, Casein kinase Iepsilon (CKIepsilon)
      and Axin/Conductin. Diversin recruits CKIepsilon to the beta-catenin degradation
      complex that consists of Axin/Conductin and GSK3beta and allows efficient
      phosphorylation of beta-catenin, thereby inhibiting beta-catenin/Tcf signals.
      Morpholino-based gene ablation in zebrafish shows that Diversin is crucial for
      axis formation, which depends on beta-catenin signaling. Diversin is also
      involved in JNK activation and gastrulation movements in zebrafish. Diversin is
      distantly related to Diego of Drosophila, which functions only in the pathway
      that controls planar cell polarity. Our data show that Diversin is an essential
      component of the Wnt-signaling pathway and acts as a molecular switch, which
      suppresses Wnt signals mediated by the canonical beta-catenin pathway and
      stimulates signaling via JNK.

PMID- 12183363
TI  - Saccharomyces forkhead protein Fkh1 regulates donor preference during mating-type
      switching through the recombination enhancer.
AB  - Saccharomyces mating-type switching results from replacement by gene conversion
      of the MAT locus with sequences copied from one of two unexpressed donor loci,
      HML or HMR. MATa cells recombine with HMLalpha approximately 90% of the time,
      whereas MATalpha cells choose HMRa 80%-90% of the time. HML preference in MATa is
      controlled by the cis-acting recombination enhancer (RE) that regulates
      recombination along the entire left arm of chromosome III. Comparison of RE
      sequences between S. cerevisiae, S. carlsbergensis, and S. bayanus defines four
      highly conserved regions (A, B, C, and D) within a 270-bp minimum RE. An adjacent
      E region enhances RE activity. Multimers of region A, D, or E are sufficient to
      promote selective use of HML. Regions A, D, and E each bind in vivo the
      transcription activator forkhead proteins Fkh1p and Fkh2p and their associated
      Ndd1p, although there are no adjacent open reading frames (ORFs). Deletion of
      FKH1 significantly reduces MATa's use of HML, as does mutation of the Fkh1/Fkh2
      binding sites in a multimer of region A. We conclude that Fkh1p regulates MATa
      donor preference through direct interaction with RE.

PMID- 12183364
TI  - Meis homeoproteins directly regulate Pax6 during vertebrate lens morphogenesis.
AB  - Pax6 is a pivotal regulator of eye development throughout Metazoa, but the direct
      upstream regulators of vertebrate Pax6 expression are unknown. In vertebrates,
      Pax6 is required for formation of the lens placode, an ectodermal thickening that
      precedes lens development. Here we show that the Meis1 and Meis2 homeoproteins
      are direct regulators of Pax6 expression in prospective lens ectoderm. In mice,
      Meis1 and Meis2 are developmentally expressed in a pattern remarkably similar to
      Pax6 and their expression is Pax6-independent. Biochemical and transgenic
      experiments reveal that Meis1 and Meis2 bind a specific sequence in the Pax6 lens
      placode enhancer that is required for its activity. Furthermore, Pax6 and Meis2
      exhibit a strong genetic interaction in lens development, and Pax6 expression is
      elevated in lenses of Meis2-overexpressing transgenic mice. When expressed in
      embryonic lens ectoderm, dominant-negative forms of Meis down-regulate endogenous
      Pax6. These results contrast with those in Drosophila, where the single Meis
      homolog, Homothorax, has been shown to negatively regulate eye formation.
      Therefore, despite the striking evolutionary conservation of Pax6 function, Pax6
      expression in the vertebrate lens is uniquely regulated.

PMID- 12183365
TI  - The Drosophila heterochromatic gene encoding poly(ADP-ribose) polymerase (PARP)
      is required to modulate chromatin structure during development.
AB  - Poly(ADP-ribose) polymerase (PARP) is a major NAD-dependent modifying enzyme that
      mediates important steps in DNA repair, transcription, and apoptosis, but its
      role during development is poorly understood. We found that a single Drosophila
      Parp gene spans more than 150 kb of transposon-rich centromeric heterochromatin
      and produces several differentially spliced transcripts, including a novel
      isoform, PARP-e, predicted to encode a protein lacking enzymatic activity. An
      insertion mutation near the upstream promoter for Parp-e disrupts all Parp
      expression. Heterochromatic but not euchromatic sequences become hypersensitive
      to micrococcal nuclease, nucleoli fail to form, and transcript levels of the
      copia retrotransposon are elevated more than 50-fold; the variegated expression
      of certain transgenes is dominantly enhanced. Larval lethality can be rescued and
      PARP activity restored by expressing a cDNA encoding PARP-e. We propose that PARP
      e autoregulates Parp transcription by influencing the chromatin structure of its
      heterochromatic environment. Our results indicate that Parp plays a fundamental
      role organizing the structure of Drosophila chromatin.

PMID- 12183366
TI  - Chromatin remodeling by RSC involves ATP-dependent DNA translocation.
AB  - Chromatin-remodeling complexes couple ATP hydrolysis to alterations in histone
      DNA interactions and nucleosome mobility, allowing transcription factors access
      to chromatin. Here, we use triple-helix strand-displacement assays, DNA length
      dependent ATPase assays, and DNA-minicircle ATPase assays to establish that RSC,
      as well as its isolated ATPase subunit Sth1, are DNA translocases. RSC/Sth1
      ATPase activity is stimulated by single-stranded DNA, suggesting that Sth1 tracks
      along one strand of the DNA duplex. Each RSC complex appears to contain a single
      molecule of Sth1, and isolated Sth1 is capable of nucleosome remodeling. We
      propose that the remodeling enzyme remains in a fixed position on the octamer and
      translocates a segment of DNA (with accompanying DNA twist), which breaks histone
      DNA contacts and propagates as a wave of DNA around the octamer. The
      demonstration of DNA translocation presented here provides a mechanistic basis
      for this DNA wave. To test the relative contribution of twist to remodeling, we
      use nucleosomes containing nicks in precise locations to uncouple twist and
      translocation. Nucleosomes bearing nicks are remodeled less efficiently than
      intact nucleosomes. These results suggest that RSC and Sth1 are DNA translocases
      that use both DNA translocation and twist to remodel nucleosomes efficiently.

PMID- 12183368
TI  - YaeL (EcfE) activates the sigma(E) pathway of stress response through a site-2
      cleavage of anti-sigma(E), RseA.
AB  - Escherichia coli YaeL (EcfE) is a homolog of human site-2 protease (S2P), a
      membrane-bound zinc metalloprotease involved in regulated intramembrane
      proteolysis. We have shown previously that YaeL, having essential metalloprotease
      active site motifs in the cytoplasmic domain, is indispensable for viability.
      Here, we obtained rpoE, encoding an extracytoplasmic stress response sigma factor
      (sigma(E)), as a multicopy suppressor against the yaeL disruption. Whereas
      sigma(E) is thought to be activated by regulated cleavage of RseA on the
      periplasmic side by the DegS protease, we found that a degradation intermediate
      of RseA consisting of the transmembrane and the cytoplasmic domains accumulated
      in the YaeL-depleted cells. This intermediate was degraded on expression of YaeL
      but not of its metalloprotease motif mutants. Cells depleted of YaeL were
      incapable of activating a sigma(E)-dependent promoter in response to an envelope
      stress. It is suggested that sigma(E) activation involves two successive
      proteolytic cleavages: first, at a periplasmic site by DegS; second, at a
      cytoplasmic or intramembrane site by YaeL. Thus, YaeL is positively required for
      the sigma(E) extracytoplasmic stress response.

PMID- 12183367
TI  - CDK-9/cyclin T (P-TEFb) is required in two postinitiation pathways for
      transcription in the C. elegans embryo.
AB  - The metazoan transcription elongation factor P-TEFb (CDK-9/cyclin T) is essential
      for HIV transcription, and is recruited by some cellular activators. P-TEFb
      promotes elongation in vitro by overcoming pausing that requires the SPT-4/SPT-5
      complex, but considerable evidence indicates that SPT-4/SPT-5 facilitates
      elongation in vivo. Here we used RNA interference to investigate P-TEFb functions
      in vivo, in the Caenorhabditis elegans embryo. We found that P-TEFb is broadly
      essential for expression of early embryonic genes. P-TEFb is required for
      phosphorylation of Ser 2 of the RNA Polymerase II C-terminal domain (CTD) repeat,
      but not for most CTD Ser 5 phosphorylation, supporting the model that P-TEFb
      phosphorylates CTD Ser 2 during elongation. Remarkably, although heat shock genes
      are cdk-9-dependent, they can be activated when spt-4 and spt-5 expression is
      inhibited along with cdk-9. This observation suggests that SPT-4/SPT-5 has an
      inhibitory function in vivo, and that mutually opposing influences of P-TEFb and
      SPT-4/SPT-5 may combine to facilitate elongation, or insure fidelity of mRNA
      production. Other genes are not expressed when cdk-9, spt-4, and spt-5 are
      inhibited simultaneously, suggesting that these genes require P-TEFb in an
      additional mechanism, and that they and heat shock genes are regulated through
      different P-TEFb-dependent elongation pathways.

PMID- 12183370
TI  - Involvement of the Polycomb-group gene Ring1B in the specification of the
      anterior-posterior axis in mice.
AB  - The products of the Polycomb group of genes form complexes that maintain the
      state of transcriptional repression of several genes with relevance to
      development and in cell proliferation. We have identified Ring1B, the product of
      the Ring1B gene (Rnf2 - Mouse Genome Informatics), by means of its interaction
      with the Polycomb group protein Mel18. We describe biochemical and genetic
      studies directed to understand the biological role of Ring1B. Immunoprecipitation
      studies indicate that Ring1B form part of protein complexes containing the
      products of other Polycomb group genes, such as Rae28/Mph1 and M33, and that this
      complexes associate to chromosomal DNA. We have generated a mouse line bearing a
      hypomorphic Ring1B allele, which shows posterior homeotic transformations of the
      axial skeleton and a mild derepression of some Hox genes (Hoxb4, Hoxb6 and Hoxb8)
      in cells anterior to their normal boundaries of expression in the mesodermal
      compartment. By contrast, the overexpression of Ring1B in chick embryos results
      in the repression of Hoxb9 expression in the neural tube. These results, together
      with the genetic interactions observed in compound Ring1B/Mel18 mutant mice, are
      consistent with a role for Ring1B in the regulation of Hox gene expression by
      Polycomb group complexes.

PMID- 12183369
TI  - DegS and YaeL participate sequentially in the cleavage of RseA to activate the
      sigma(E)-dependent extracytoplasmic stress response.
AB  - All cells have stress response pathways that maintain homeostasis in each
      cellular compartment. In the Gram-negative bacterium Escherichia coli, the
      sigma(E) pathway responds to protein misfolding in the envelope. The stress
      signal is transduced across the inner membrane to the cytoplasm via the inner
      membrane protein RseA, the anti-sigma factor that inhibits the transcriptional
      activity of sigma(E). Stress-induced activation of the pathway requires the
      regulated proteolysis of RseA. In this report we show that RseA is degraded by
      sequential proteolytic events controlled by the inner membrane-anchored protease
      DegS and the membrane-embedded metalloprotease YaeL, an ortholog of mammalian
      Site-2 protease (S2P). This is consistent with the mechanism of activation of
      ATF6, the mammalian unfolded protein response transcription factor by Site-1
      protease and S2P. Thus, mammalian and bacterial cells employ a conserved
      proteolytic mechanism to activate membrane-associated transcription factors that
      initiate intercompartmental cellular stress responses.

PMID- 12183371
TI  - Cell polarity and locomotion, as well as endocytosis, depend on NSF.
AB  - NEM-sensitive factor (NSF) is an essential protein required during membrane
      transport. We replaced part of the endogenous D. discoideum NSF gene (nsfA) by a
      PCR-mutagenised library and isolated 11 mutants temperature-sensitive (ts) for
      growth. Two of these have been studied in detail. As expected, both are ts for
      FITC-dextran uptake by macropinocytosis, for internalising their surface membrane
      (monitored with FM1-43) and for phagocytosis. However, after 10-20 minutes at 28
      degrees C, they round up and cease to chemotax, move or cap ConA receptors. They
      fully recover when returned to 22 degrees C. These cells carry out a normal
      'cringe' reaction in response to cAMP, indicating that the actin cytoskeleton and
      this signal transduction pathway are still functional at 28 degrees C. The
      behaviour of these mutants shows that NSF-catalysed processes are required not
      only for the different endocytic cycles but also for the maintenance of cell
      polarity. As cell locomotion depends on a cell having a polarity, the mutants
      stop moving at high temperature. A tentative model is proposed to explain the
      surprising link between membrane recycling and cell polarity revealed here.

PMID- 12183372
TI  - Formation of neuroblasts in the embryonic central nervous system of Drosophila
      melanogaster is controlled by SoxNeuro.
AB  - Sox proteins form a family of HMG-box transcription factors related to the
      mammalian testis determining factor SRY. Sox-mediated modulation of gene
      expression plays an important role in various developmental contexts. Drosophila
      SoxNeuro, a putative ortholog of the vertebrate Sox1, Sox2 and Sox3 proteins, is
      one of the earliest transcription factors to be expressed pan-neuroectodermally.
      We demonstrate that SoxNeuro is essential for the formation of the neural
      progenitor cells in central nervous system. We show that loss of function
      mutations of SoxNeuro are associated with a spatially restricted hypoplasia:
      neuroblast formation is severely affected in the lateral and intermediate regions
      of the central nervous system, whereas ventral neuroblast formation is almost
      normal. We present evidence that a requirement for SoxNeuro in ventral neuroblast
      formation is masked by a functional redundancy with Dichaete, a second Sox
      protein whose expression partially overlaps that of SoxNeuro. Genetic
      interactions of SoxNeuro and the dorsoventral patterning genes ventral nerve
      chord defective and intermediate neuroblasts defective underlie ventral and
      intermediate neuroblast formation. Finally, the expression of the Achaete-Scute
      gene complex suggests that SoxNeuro acts upstream and in parallel with the
      proneural genes.

PMID- 12183373
TI  - Dephrin, a transmembrane ephrin with a unique structure, prevents interneuronal
      axons from exiting the Drosophila embryonic CNS.
AB  - Ephrin/Eph signalling is crucial for axonal pathfinding in vertebrates and
      invertebrates. We identified the Drosophila ephrin orthologue, Dephrin, and
      describe for the first time the role of ephrin/Eph signalling in the embryonic
      central nervous system (CNS). Dephrin is a transmembrane ephrin with a unique N
      terminus and an ephrinB-like cytoplasmic tail. Dephrin binds and interacts with
      DEph, the Drosophila Eph-like receptor, and Dephrin and DEph are confined to
      different neuronal compartments. Loss of Dephrin or DEph causes the abberant exit
      of interneuronal axons from the CNS, whereas ectopic expression of Dephrin halts
      axonal growth. We propose that the longitudinal tracts in the Drosophila CNS are
      moulded by a repulsive outer border of Dephrin expression.

PMID- 12183374
TI  - Evidence for differential and redundant function of the Sox genes Dichaete and
      SoxN during CNS development in Drosophila.
AB  - Group B Sox-domain proteins encompass a class of conserved DNA-binding proteins
      expressed from the earliest stages of metazoan CNS development. In all higher
      organisms studied to date, related Group B Sox proteins are co-expressed in the
      developing CNS; in vertebrates there are three (Sox1, Sox2 and Sox3) and in
      Drosophila there are two (SoxNeuro and Dichaete). It has been suggested there may
      be a degree of functional redundancy in Sox function during CNS development. We
      describe the CNS phenotype of a null mutation in the Drosophila SoxNeuro gene and
      provide the first direct evidence for both redundant and differential Sox
      function during CNS development in Drosophila. In the lateral neuroectoderm,
      where SoxNeuro is uniquely expressed, SoxNeuro mutants show a loss or reduction
      of achaete expression as well as a loss of many correctly specified lateral
      neuroblasts. By contrast, in the medial neuroectoderm, where the expression of
      SoxNeuro and Dichaete overlaps, the phenotypes of both single mutants are mild.
      In accordance with an at least partially redundant function in that region,
      SoxNeuro/Dichaete double mutant embryos show a severe neural hypoplasia
      throughout the central nervous system, as well as a dramatic loss of achaete
      expressing proneural clusters and medially derived neuroblasts. However, the
      finding that Dichaete and SoxN exhibit opposite effects on achaete expression
      within the intermediate neuroectoderm demonstrates that each protein also has
      region-specific unique functions during early CNS development in the Drosophila
      embryo.

PMID- 12183375
TI  - Lhx4 and Prop1 are required for cell survival and expansion of the pituitary
      primordia.
AB  - Deficiencies in the homeobox transcription factors LHX4 and PROP1 cause pituitary
      hormone deficiency in both humans and mice. Lhx4 and Prop1 mutants exhibit severe
      anterior pituitary hypoplasia resulting from limited differentiation and
      expansion of most specialized cell types. Little is known about the mechanism
      through which these genes promote pituitary development. In this study we
      determined that the hypoplasia in Lhx4 mutants results from increased cell death
      and that the reduced differentiation is attributable to a temporal shift in Lhx3
      activation. In contrast, Prop1 mutants exhibit normal cell proliferation and cell
      survival but show evidence of defective dorsal-ventral patterning. Molecular
      genetic analyses reveal that Lhx4 and Prop1 have overlapping functions in early
      pituitary development. Double mutants exhibit delayed corticotrope specification
      and complete failure of all other anterior pituitary cell types to differentiate.
      Thus, Lhx4 and Prop1 have critical, but mechanistically different roles in
      specification and expansion of specialized anterior pituitary cells.

PMID- 12183377
TI  - The chemokine SDF1 regulates migration of dentate granule cells.
AB  - The dentate gyrus is the primary afferent pathway into the hippocampus, but there
      is little information concerning the molecular influences that govern its
      formation. In particular, the control of migration and cell positioning of
      dentate granule cells is not clear. We have characterized more fully the timing
      and route of granule cell migration during embryogenesis using in utero
      retroviral injections. Using this information, we developed an in vitro assay
      that faithfully recapitulates important events in dentate gyrus morphogenesis. In
      searching for candidate ligands that may regulate dentate granule cell migration,
      we found that SDF1, a chemokine that regulates cerebellar and leukocyte
      migration, and its receptor CXCR4 are expressed in patterns that suggest a role
      in dentate granule cell migration. Furthermore, CXCR4 mutant mice have a defect
      in granule cell position. Ectopic expression of SDF1 in our explant assay showed
      that it directly regulates dentate granule cell migration. Our study shows that a
      chemokine is necessary for the normal development of the dentate gyrus, a
      forebrain structure crucial for learning and memory.

PMID- 12183376
TI  - Differential requirement for STAT by gain-of-function and wild-type receptor
      tyrosine kinase Torso in Drosophila.
AB  - Malignant transformation frequently involves aberrant signaling from receptor
      tyrosine kinases (RTKs). These receptors commonly activate Ras/Raf/MEK/MAPK
      signaling but when overactivated can also induce the JAK/STAT pathway, originally
      identified as the signaling cascade downstream of cytokine receptors.
      Inappropriate activation of STAT has been found in many human cancers. However,
      the contribution of the JAK/STAT pathway in RTK signaling remains unclear. We
      have investigated the requirement of the JAK/STAT pathway for signaling by wild
      type and mutant forms of the RTK Torso (Tor) using a genetic approach in
      Drosophila. Our results indicate that the JAK/STAT pathway plays little or no
      role in signaling by wild-type Tor. In contrast, we find that STAT, encoded by
      marelle (mrl; DStat92E), is essential for the gain-of-function mutant Tor
      (Tor(GOF)) to activate ectopic gene expression. Our findings indicate that the
      Ras/Raf/MEK/MAPK signaling pathway is sufficient to mediate the normal functions
      of wild-type RTK, whereas the effects of gain-of-function mutant RTK additionally
      require STAT activation.

PMID- 12183378
TI  - Connecting Hh, Dpp and EGF signalling in patterning of the Drosophila wing; the
      pivotal role of collier/knot in the AP organiser.
AB  - Hedgehog (Hh) signalling from posterior (P) to anterior (A) cells is the primary
      determinant of AP polarity in the limb field in insects and vertebrates. Hh acts
      in part by inducing expression of Decapentaplegic (Dpp), but how Hh and Dpp
      together pattern the central region of the Drosophila wing remains largely
      unknown. We have re-examined the role played by Collier (Col), a dose-dependent
      Hh target activated in cells along the AP boundary, the AP organiser in the
      imaginal wing disc. We found that col mutant wings are smaller than wild type and
      lack L4 vein, in addition to missing the L3-L4 intervein and mis-positioning of
      the anterior L3 vein. We link these phenotypes to col requirement for the local
      upregulation of both emc and N, two genes involved in the control of cell
      proliferation, the EGFR ligand Vein and the intervein determination gene
      blistered. We further show that attenuation of Dpp signalling in the AP organiser
      is also col dependent and, in conjunction with Vein upregulation, required for
      formation of L4 vein. A model recapitulating the molecular interplay between the
      Hh, Dpp and EGF signalling pathways in the wing AP organiser is presented.

PMID- 12183379
TI  - Eye suppression, a novel function of teashirt, requires Wingless signaling.
AB  - teashirt (tsh) encodes a Drosophila zinc-finger protein. Misexpression of tsh has
      been shown to induce ectopic eye formation in the antenna. We report that tsh can
      suppress eye development. This novel function of tsh is due to the induction of
      homothorax (hth), a known repressor of eye development, and requires Wingless
      (WG) signaling. Interestingly, tsh has different functions in the dorsal and
      ventral eye, suppressing eye development close to the ventral margin, while
      promoting eye development near the dorsal margin. It affects both growth of eye
      disc and retinal cell differentiation.

PMID- 12183380
TI  - SUPERMAN attenuates positive INNER NO OUTER autoregulation to maintain polar
      development of Arabidopsis ovule outer integuments.
AB  - The outer integument of Arabidopsis ovules exhibits marked polarity in its
      development, growing extensively from the abaxial side, but only to a very
      limited extent from the adaxial side of the ovule. Mutations in two genes affect
      this asymmetric growth. In strong inner no outer (ino) mutants outer integument
      growth is eliminated, whereas in superman (sup) mutants integument growth on the
      adaxial side is nearly equal to wild-type growth on the abaxial side. Through
      complementation and reporter gene analysis, a region of INO 5'-flanking sequences
      was identified that contains sufficient information for appropriate expression of
      INO. Using this INO promoter (P-INO) we show that INO acts as a positive
      regulator of transcription from P-INO, but is not sufficient for de novo
      initiation of transcription in other plant parts. Protein fusions demonstrate
      nuclear localization of INO, consistent with a proposed role as a transcription
      factor for this member of the YABBY protein family. Through its ability to
      inhibit expression of the endogenous INO gene and transgenes driven by P-INO, SUP
      is shown to be a negative regulator of INO transcription. Substitution of another
      YABBY protein coding region (CRABS CLAW) for INO overcomes this negative
      regulation, indicating that SUP suppresses INO transcription through attenuation
      of the INO positive autoregulatory loop.

PMID- 12183381
TI  - NOZZLE links proximal-distal and adaxial-abaxial pattern formation during ovule
      development in Arabidopsis thaliana.
AB  - The ovules of Arabidopsis show polarity along the proximal-distal and the adaxial
      abaxial axis. NOZZLE, a gene that encodes a novel protein and BELL1, encoding a
      homeodomain protein, play a vital role in pattern formation along the proximal
      distal axis. INNER NO OUTER, which encodes a member of the YABBY family of
      transcription factors and SUPERMAN, encoding a zinc finger transcription factor,
      are essential for the establishment and maintenance of adaxial-abaxial polarity.
      To date, the co-ordination of patterning along these two axes is unclear. Here we
      show that NOZZLE plays a vital role in pattern formation along the adaxial
      abaxial axis as well. We investigated the expression of INNER NO OUTER in various
      mutant backgrounds and have identified ABERRANT TESTA SHAPE and NOZZLE as spatial
      regulators of INNER NO OUTER expression. In addition, we show that NOZZLE and
      AINTEGUMENTA, which encodes an AP2 domain transcription factor, regulate the
      temporal expression of INNER NO OUTER and that BELL1 is essential for INNER NO
      OUTER expression. We further analysed the expression of BELL1 and AINTEGUMENTA in
      inner no outer mutants and show that the positive auto-regulatory control of
      INNER NO OUTER expression involves AINTEGUMENTA. Based on our results we propose
      a model for adaxial-abaxial pattern formation during ovule development. Our
      results indicate that NOZZLE plays a central role in patterning both the proximal
      distal and the adaxial-abaxial axes. Furthermore, negatively regulating INO
      expression in a temporal manner, ensures that the adaxial-abaxial polarity is
      established after the specification of the chalaza, a proximal-distal axis
      pattern element. It therefore serves as a molecular link between these processes
      during ovule development in Arabidopsis thaliana.

PMID- 12183382
TI  - Negative effect of Hox gene expression on the development of the neural crest
      derived facial skeleton.
AB  - Diencephalic, mesencephalic and metencephalic neural crest cells are skeletogenic
      and derive from neural folds that do not express Hox genes. In order to examine
      the influence of Hox gene expression on skull morphogenesis, expression of Hoxa2,
      Hoxa3 and Hoxb4 in conjunction with that of the green fluorescent protein has
      been selectively targeted to the Hox-negative neural folds of the avian embryo
      prior to the onset of crest cell emigration. Hoxa2 expression precludes the
      development of the entire facial skeleton. Transgenic Hoxa2 embryos such as those
      from which the Hox-negative domain of the cephalic neural crest has been removed
      have no upper or lower jaws and no frontonasal structures. Embryos subjected to
      the forced expression of Hoxa3 and Hoxb4 show severe defects in the facial
      skeleton but not a complete absence of facial cartilage. Hoxa3 prevents the
      formation of the skeleton derived from the first branchial arch, but allows the
      development (albeit reduced) of the nasal septum. Hoxb4, by contrast, hampers the
      formation of the nasal bud-derived skeleton, while allowing that of a proximal
      (but not distal) segment of the lower jaw. The combined effect of Hoxa3 and Hoxb4
      prevents the formation of facial skeletal structures, comparable with Hoxa2. None
      of these genes impairs the formation of neural derivatives of the crest. These
      results suggest that over the course of evolution, the absence of Hox gene
      expression in the anterior part of the chordate embryo was crucial in the
      vertebrate phylum for the development of a face, jaws and brain case, and, hence,
      also for that of the forebrain.

PMID- 12183383
TI  - Cortical granule translocation is microfilament mediated and linked to meiotic
      maturation in the sea urchin oocyte.
AB  - Cortical granules exocytose after the fusion of egg and sperm in most animals,
      and their contents function in the block to polyspermy by creating an
      impenetrable extracellular matrix. Cortical granules are synthesized throughout
      oogenesis and translocate en masse to the cell surface during meiosis where they
      remain until fertilization. As the mature oocyte is approximately 125 micro m in
      diameter (Lytechinus variegatus), many of the cortical granules translocate
      upwards of 60 micro m to reach the cortex within a 4 hour time window. We have
      investigated the mechanism of this coordinated vesicular translocation event.
      Although the stimulus to reinitiate meiosis in sea urchin oocytes is not known,
      we found many different ways to reversibly inhibit germinal vesicle breakdown,
      and used these findings to discover that meiotic maturation and cortical granule
      translocation are inseparable. We also learned that cortical granule
      translocation requires association with microfilaments but not microtubules. It
      is clear from endocytosis assays that microfilament motors are functional prior
      to meiosis, even though cortical granules do not use them. However, just after
      GVBD, cortical granules attach to microfilaments and translocate to the cell
      surface. This latter conclusion is based on organelle stratification within the
      oocyte followed by positional quantitation of the cortical granules. We conclude
      from these studies that maturation promoting factor (MPF) activation stimulates
      vesicle association with microfilaments, and is a key regulatory step in the
      coordinated translocation of cortical granules to the egg cortex.

PMID- 12183384
TI  - SCHIZORIZA controls an asymmetric cell division and restricts epidermal identity
      in the Arabidopsis root.
AB  - The primary root of Arabidopsis has a simple cellular organisation. The fixed
      radial cell pattern results from stereotypical cell divisions that occur in the
      meristem. Here we describe the characterisation of schizoriza (scz), a mutant
      with defective radial patterning. In scz mutants, the subepidermal layer (ground
      tissue) develops root hairs. Root hairs normally only form on epidermal cells of
      wild-type plants. Moreover, extra periclinal divisions (new wall parallel to
      surface of the root) occur in the scz root resulting in the formation of
      supernumerary layers in the ground tissue. Both scarecrow (scr) and short root
      (shr) suppress the extra periclinal divisions characteristic of scz mutant roots.
      This results in the formation of a single layered ground tissue in the double
      mutants. Cells of this layer develop root hairs, indicating that mis
      specification of the ground tissue in scz mutants is uncoupled to the cell
      division defect. This suggests that during the development of the ground tissue
      SCZ has two distinct roles: (1) it acts as a suppressor of epidermal fate in the
      ground tissue, and (2) it is required to repress periclinal divisions in the
      meristem. It may act in the same pathway as SCR and SHR.

PMID- 12183385
TI  - Distinct roles for Fgf, Wnt and retinoic acid in posteriorizing the neural
      ectoderm.
AB  - Early neural patterning in vertebrates involves signals that inhibit anterior (A)
      and promote posterior (P) positional values within the nascent neural plate. In
      this study, we have investigated the contributions of, and interactions between,
      retinoic acid (RA), Fgf and Wnt signals in the promotion of posterior fates in
      the ectoderm. We analyze expression and function of cyp26/P450RAI, a gene that
      encodes retinoic acid 4-hydroxylase, as a tool for investigating these events.
      Cyp26 is first expressed in the presumptive anterior neural ectoderm and the
      blastoderm margin at the late blastula. When the posterior neural gene hoxb1b is
      expressed during gastrulation, it shows a strikingly complementary pattern to
      cyp26. Using these two genes, as well as otx2 and meis3 as anterior and posterior
      markers, we show that Fgf and Wnt signals suppress expression of anterior genes,
      including cyp26. Overexpression of cyp26 suppresses posterior genes, suggesting
      that the anterior expression of cyp26 is important for restricting the expression
      of posterior genes. Consistent with this, knock-down of cyp26 by morpholino
      oligonucleotides leads to the anterior expansion of posterior genes. We further
      show that Fgf- and Wnt-dependent activation of posterior genes is mediated by RA,
      whereas suppression of anterior genes does not depend on RA signaling. Fgf and
      Wnt signals suppress cyp26 expression, while Cyp26 suppresses the RA signal.
      Thus, cyp26 has an important role in linking the Fgf, Wnt and RA signals to
      regulate AP patterning of the neural ectoderm in the late blastula to gastrula
      embryo in zebrafish.

PMID- 12183386
TI  - Genetic modifiers of otocephalic phenotypes in Otx2 heterozygous mutant mice.
AB  - Mice heterozygous for the Otx2 mutation display a craniofacial malformation,
      known as otocephaly or agnathia-holoprosencephaly complex. The severity of the
      phenotype is dependent on the genetic background of a C57BL/6 (B6) strain; most
      of the offspring of Otx2 knock-out chimeras, which are equivalent to the F(1) of
      CBA and B6 strains, backcrossed with B6 females display reduction or loss of
      mandible, whereas those backcrossed with CBA females do not show noticeable
      phenotype at birth. The availability of phenotypically disparate strains renders
      identification of Otx2 modifier loci possible. In this study, a backcross of
      chimera with B6 was generated and genome-wide scans were conducted with
      polymorphic markers for non-mendelian distribution of alleles in Otx2
      heterozygous mutant mice displaying abnormalities in the lower jaw. We identified
      one significant locus, Otmf18, between D18Mit68 and D18Mit120 on chromosomes 18,
      linked to the mandibular phenotype (LOD score 3.33). A similar replication
      experiment using a second backcross (N3) mouse demonstrated the presence of
      another significant locus, Otmf2 between D2Mit164 and D2Mit282 on chromosome 2,
      linked to the mandibular phenotype (LOD score 3.93). These two modifiers account
      for the distribution of the craniofacial malformations by the genetic effect
      between B6 and CBA strains. Moreover, Otmf2 contain a candidate gene for several
      diseases in mice and humans. These genetic studies involving an otocephalic mouse
      model appear to provide new insights into mechanistic pathways of craniofacial
      development. Furthermore, these experiments offer a powerful approach with
      respect to identification and characterization of candidate genes that may
      contribute to human agnathia-holoprosencephaly complex diseases.

PMID- 12183387
TI  - Characterization of zebrafish merlot/chablis as non-mammalian vertebrate models
      for severe congenital anemia due to protein 4.1 deficiency.
AB  - The red blood cell membrane skeleton is an elaborate and organized network of
      structural proteins that interacts with the lipid bilayer and transmembrane
      proteins to maintain red blood cell morphology, membrane deformability and
      mechanical stability. A crucial component of red blood cell membrane skeleton is
      the erythroid specific protein 4.1R, which anchors the spectrin-actin based
      cytoskeleton to the plasma membrane. Qualitative and quantitative defects in
      protein 4.1R result in congenital red cell membrane disorders characterized by
      reduced cellular deformability and abnormal cell morphology. The zebrafish
      mutants merlot (mot) and chablis (cha) exhibit severe hemolytic anemia
      characterized by abnormal cell morphology and increased osmotic fragility. The
      phenotypic analysis of merlot indicates severe hemolysis of mutant red blood
      cells, consistent with the observed cardiomegaly, splenomegaly, elevated
      bilirubin levels and erythroid hyperplasia in the kidneys. The result of electron
      microscopic analysis demonstrates that mot red blood cells have membrane
      abnormalities and exhibit a severe loss of cortical membrane organization. Using
      positional cloning techniques and a candidate gene approach, we demonstrate that
      merlot and chablis are allelic and encode the zebrafish erythroid specific
      protein 4.1R. We show that mutant cDNAs from both alleles harbor nonsense point
      mutations, resulting in premature stop codons. This work presents merlot/chablis
      as the first characterized non-mammalian vertebrate models of hereditary anemia
      due to a defect in protein 4.1R integrity.

PMID- 12183388
TI  - Homeostatic maintenance of neuronal excitability by burst discharges in vivo.
AB  - Information in neuronal networks is thought to be represented by the rate of
      discharge and the temporal relationship between the discharging neurons. The
      discharge frequency of neurons is affected by their afferents and intrinsic
      properties, and shows great individual variability. The temporal coordination of
      neurons is greatly facilitated by network oscillations. In the hippocampus,
      population synchrony fluctuates during theta and gamma oscillations (10-100 ms
      scale) and can increase almost 10-fold during sharp wave bursts. Despite these
      large changes in excitability in the sub-second scale, longer-term (minute-scale)
      firing rates of individual neurons are relatively constant in an unchanging
      environment. As a result, mean hippocampal output remains stable over time. To
      understand the mechanisms responsible for this homeostasis, we address the
      following issues: (i) Can firing rates of single cells be modified? (ii) Once
      modified, what mechanism(s) can maintain the changes? We show that firing rates
      of hippocampal pyramidal cells can be altered in a novel environment and by
      Hebbian pairing of physiological input patterns with postsynaptic burst
      discharge. We also illustrate a competition between single spikes and the
      occurrence of spike bursts. Since spike-inducing (suprathreshold) inputs decrease
      the ability of strong ('teaching') inputs to induce a burst discharge, we propose
      that the single spike versus burst competition presents a homeostatic regulatory
      mechanism to maintain synaptic strength and, consequently, firing rate in
      pyramidal cells.

PMID- 12183389
TI  - Hippocampal and brain stem activation during word retrieval after repeated and
      semantic encoding.
AB  - Repeated word presentation during learning and the use of a semantic encoding
      task both increase the accuracy of subsequent word retrieval. Previous
      neuroimaging studies have shown that successful word retrieval depends on the
      recruitment of the hippocampus, whereas the effort of retrieval is linked to
      activation of prefrontal cortex modules. We studied the effects of repetition (4x
      versus 1x presentation) and encoding task (semantic versus perceptual) on
      hippocampal and prefrontal cortex activation during word-stem cued recall using
      positron emission tomography. Repeated and semantic encoding resulted in
      increased recall accuracy, with word repetition showing a greater effect when
      using a semantic encoding task. The more successful retrieval of words presented
      repeatedly compared with words presented once was associated with activation of
      the left anterior hippocampus. The more successful retrieval of words encoded
      using a semantic compared with a perceptual task was associated with activation
      of the right posterior and, less significantly, the left anterior hippocampus.
      The greater benefit of repeated learning when using the semantic task was linked
      to activation of the right brainstem, in the region of the ventral tegmentum. Our
      results suggest that word repetition and semantic encoding increase recall
      accuracy during subsequent word retrieval via distinct hippocampal mechanisms and
      that ventral tegmentum activation is relevant for word retrieval after semantic
      encoding. These findings confirm the importance of hippocampal recruitment during
      word retrieval and provide novel evidence for a role of brainstem neurons in word
      retrieval after semantic encoding.

PMID- 12183390
TI  - The role of the frontal cortex in task preparation.
AB  - The ability to prepare a task is crucial for the voluntary control of our
      actions. It enables us to react flexibly and rapidly to a changing environment.
      In the present event-related functional magnetic resonance imaging study we
      investigated task preparation with a task-cueing paradigm. In this paradigm we
      intermixed trials in which a task cue and a target were presented with trials in
      which only the task cue was presented. Analysis of these cue-only trials allowed
      us to isolate task-preparation related control from execution-related control
      processes. By means of this paradigm, we could demonstrate that a frontal network
      was related to task preparation. Further analysis revealed that the fronto
      lateral cortex at the junction of precentral sulcus and inferior frontal sulcus
      and the presupplementary motor area are the crucial frontal components in task
      preparation.

PMID- 12183391
TI  - Color contrast in macaque V1.
AB  - We explored the neural basis for spatial color contrast (red looks redder
      surrounded by green) and temporal color contrast (red looks redder if preceded by
      green) in primary visual cortex (V1) of the alert macaque. Using pairs of
      stimuli, we found a subset of neurons that gave stronger responses to sequences
      of red and green spots and stronger responses to adjacent red and green spots.
      These cells combined their cone inputs linearly: for a red-ON-center cell, the
      sum of the OFF response to green and the ON response to red predicted the peak
      response to red preceded by green. These 'color' cells, which could underlie hue
      discrimination because they show cone opponency, could mediate spatial and
      temporal color contrast. In contrast, the majority of cortical cells, which do
      not show overt cone opponency but which are often orientation tuned and/or
      direction selective, are by themselves incapable of mediating hue discrimination.
      The remarkable degree of specialization shown by cells in V1, especially that of
      the double-opponent color cells, is discussed.

PMID- 12183392
TI  - Basal-ganglia 'projections' to the prefrontal cortex of the primate.
AB  - We used retrograde transneuronal transport of the McIntyre-B strain of herpes
      simplex virus type 1 to examine the extent and organization of basal-ganglia
      thalamocortical projections to five regions of prefrontal cortex in the cebus
      monkey (Cebus apella): medial and lateral area 9 (9m and 9l), dorsal and ventral
      area 46 (46d and 46v) and lateral area 12 (12l). All of these prefrontal areas
      were found to be targets of basal-ganglia output that originated in the internal
      segment of the globus pallidus (GPi) and/or the pars reticulata of the substantia
      nigra (SNpr). Approximately one-third of the total volume of these nuclei was
      directed toward prefrontal cortex, a volume comparable to that directed at the
      cortical motor areas. The origins of the outputs to different prefrontal areas
      were topographically organized. Different portions of SNpr (the rostral and
      caudal thirds) projected to areas 9m and 12l. Similarly, different output nuclei
      (GPi and SNpr) projected to adjacent portions of the same cytoarchitectonic field
      (46d and 46v). Furthermore, the outputs to prefrontal areas were segregated from
      those to motor areas of cortex. Thus, basal-ganglia outputs to prefrontal cortex
      are both extensive and topographically organized, forming a rich anatomical
      substrate for basal-ganglia influences on the cognitive operations of the frontal
      lobe.

PMID- 12183393
TI  - Synaptic connections and small circuits involving excitatory and inhibitory
      neurons in layers 2-5 of adult rat and cat neocortex: triple intracellular
      recordings and biocytin labelling in vitro.
AB  - Dual and triple intracellular recordings with biocytin labelling in slices of
      adult neocortex explored small circuits of synaptically connected neurons. 679
      paired recordings in rat and 319 in cat yielded 135 and 42 excitatory
      postsynaptic potentials (EPSPs) and 37 and 26 inhibitory postsynaptic potentials
      (IPSPs), respectively. Patterns of connectivity and synaptic properties were
      similar in the two species, although differences of scale and in the range of
      morphologies were observed. Excitatory 'forward' projections from layer 4 to 3,
      like those from layer 3 to 5, targeted pyramidal cells and a small proportion of
      interneurons, while excitatory 'back' projections from layer 3 to 4 selected
      interneurons, including parvalbumin immuno-positive basket cells. Layer 4
      interneurons that inhibited layer 3 pyramidal cells included both basket cells
      and dendrite-targeting cells. Large interneurons, resembling cells previously
      described as large basket cells, in layers 4 and 3 (cat), with long myelinated
      horizontal axon collaterals received frequent excitatory inputs from both layers.
      A very high rate of connectivity was observed between pairs of interneurons,
      often with quite different morphologies, and the resultant IPSPs, like the EPSPs
      recorded in interneurons, were brief compared with those recorded in pyramidal
      and spiny stellate cells.

PMID- 12183394
TI  - Altered spatial arrangement of layer V pyramidal cells in the mouse brain
      following prenatal low-dose X-irradiation. A stereological study using a novel
      three-dimensional analysis method to estimate the nearest neighbor distance
      distributions of cells in thick sections.
AB  - Prenatal X-irradiation, even at doses <1 Gy, can induce spatial disarray of
      neurons in the brains of offspring, possibly due to disturbed neuronal migration.
      Here we analyze the effects of prenatal low-dose X-irradiation using a novel
      stereological method designed to investigate the three-dimensional (3D) spatial
      arrangement of neurons in thick sections. Pregnant mice were X-irradiated with 50
      cGy on embryonic day 13 or were sham-irradiated. The right brain halves of their
      180-day-old offspring were dissected into entire series of 150 microm thick
      frontal cryostat sections and stained with gallocyanin. Approximately 700 layer V
      pyramidal cells per animal were sampled in a systematic-random manner in the
      middle of the section's thickness. The x-y-z coordinates of these 'parent
      neurons' were recorded, as well as of all neighboring (up to 10) 'offspring
      neurons' close to each 'parent neuron'. From these data, the nearest neighbor
      distance (NND) distributions for layer V pyramidal cells were calculated. Using
      this novel 3D analysis method, we found that, in comparison to controls, prenatal
      X-irradiation had no effect on the total neuron number, but did cause a reduction
      in the mean volume of layer V by 26.5% and a more dispersed spatial arrangement
      of these neurons. Considering the recent literature, it seems reasonable to
      consider abnormal neuronal migration as the potential basic cause of this
      finding.

PMID- 12183395
TI  - Enrichment of mGluR7a in the presynaptic active zones of GABAergic and non
      GABAergic terminals on interneurons in the rat somatosensory cortex.
AB  - The release of glutamate and GABA is modulated by presynaptic metabotropic
      glutamate receptors (mGluRs). We used immunocytochemical methods to define the
      location of the group III receptor mGluR7a in glutamatergic and GABAergic
      terminals innervating GABAergic interneurons and pyramidal cells.
      Immunoreactivity for mGluR7a was localized in the presynaptic active zone of both
      identified GABAergic and presumed glutamatergic terminals. Terminals innervating
      dendritic spines showed a variable level of receptor immunoreactivity, ranging
      from immunonegative to strongly immunopositive. The frequency of strongly mGluR7a
      positive terminals innervating the soma and dendrites of mGluR1
      alpha/somatostatin-expressing interneurons was very high relative to other
      neurons. On dendrites that received mGluR7a-enriched glutamatergic innervation,
      at least 80% of GABAergic terminals were immunopositive for mGluR7a. On such
      dendrites virtually all (95%) vasoactive intestinal polypeptide (VIP) positive
      (GABAergic) terminals were enriched in mGluR7a. The targets of VIP/mGluR7a
      expressing terminals were mainly (88%) mGluR1 alpha-expressing interneurons,
      which were mostly somatostatin immunopositive. Parvalbumin positive terminals
      were immunonegative for mGluR7a. Some parvalbumin immunoreactive dendrites
      received strongly mGluR7a positive terminals. The subcellular location, as well
      as the cell type and synapse-specific distribution of mGluR7a in isocortical
      neuronal circuits, is homologous to its distribution in the hippocampus. The
      specific location of mGluR7a in the presynaptic active zone of both glutamatergic
      and GABAergic synapses may be related to the proximity of calcium channels and
      the vesicle fusion machinery. The enrichment of mGluR7a in the main GABAergic, as
      well as in the glutamatergic, innervation of mGluR1 alpha/somatostatin-expressing
      interneurons suggests that their activation is under unique regulation by
      extracellular glutamate.

PMID- 12183396
TI  - Neonatal hippocampal damage alters electrophysiological properties of prefrontal
      cortical neurons in adult rats.
AB  - A neonatal excitotoxic lesion of the ventral hippocampus in the rat produces a
      variety of behavioral and cellular changes that remain latent until early
      adulthood. These delayed effects resemble many phenomena observed in
      schizophrenia, a neuropsychiatric disorder of early adult onset in which abnormal
      development of the hippocampus and prefrontal cortex has been postulated. Here we
      investigated the impact of this neonatal hippocampal lesion on the response of
      medial prefrontal cortical pyramidal neurons to specific afferent stimulation.
      Neonatal hippocampal damage altered the physiological responses of these neurons
      to electrical stimulation of midbrain dopaminergic-GABAergic projections, but not
      thalamic glutamatergic afferents. The lesion resulted in excessive firing of
      pyramidal neurons in response to mesocortical stimulation and this effect was not
      observed before adulthood or after similar hippocampal damage produced in adult
      rats. These data show that neonatal damage to the ventral hippocampus changes, in
      a developmentally specific manner, the nature of prefrontal cortical neuron
      responses to activation of projections from the ventral tegmental area, an effect
      that may explain the adverse impact of stress in schizophrenia.

PMID- 12183397
TI  - Reduced N-acetylaspartate in prefrontal cortex of adult rats with neonatal
      hippocampal damage.
AB  - Previous studies in animals suggested that neonatal lesions of the ventral
      hippocampus disrupt development of prefrontal cortex and its regulation of
      dopaminergic activity. In the present study, we assayed an in vivo chemical
      marker of neuronal integrity (proton magnetic resonance spectroscopy signal of N
      acetylaspartate, NAA) in prefrontal cortex and striatum of rats with neonatal
      excitotoxic lesions of the ventral hippocampus. We also measured in post-mortem
      tissue expression of EAAC1 mRNA, a molecular marker of intrinsic neurons. In the
      cohort studied at juvenile age and again at young adulthood [postnatal day (PD)
      37 and 71], we found selective reductions of NAA in the prefrontal cortex only at
      PD 71. Emergence of neuronal pathology was temporally associated with emergence
      of amphetamine-induced hyperlocomotion. Reduced prefrontal NAA was confirmed in
      the second cohort studied at an older age (PD 120). Expression of EAAC1 mRNA was
      significantly reduced in prefrontal cortex of the lesioned rats. No changes in
      NAA were found in the striatum in either cohort and cortical area size was not
      changed. These results suggest that early ventral hippocampal lesions produce
      developmental neuronal pathology in prefrontal cortex that is temporally
      associated with dysregulation of dopamine behaviors and is reminiscent of the
      temporal profile of the onset of schizophrenia.

PMID- 12183398
TI  - Eye position signals modulate early dorsal and ventral visual areas.
AB  - An internal sense of eye position is necessary to maintain the constancy of the
      visual world in spite of movements of the eyes. Neuroimaging studies have
      localized human homologs of monkey visual motion processing areas in MT/MST and
      also in the collateral sulcus (V4), an area that codes features within objects.
      We show that these two areas have a baseline fMRI signal that is modulated by eye
      position and that the preferred direction of the eye position signal is different
      in the two areas; increasing for ipsiversive eye positions in MT/MST and
      increasing for contraversive eye positions within the collateral sulcus. This
      baseline modulation is a true eye position signal; one that is present in the
      absence of visual motion stimuli. The difference in the preferred direction of
      the eye position signal may reflect the different transformations in these two
      areas; a transformation from a retinotopic (eye-centered) to an egocentric
      coordinate frame necessary for guiding action and to an object-centered frame for
      object recognition.

PMID- 12183399
TI  - Sex differences in temporo-limbic and frontal brain volumes of healthy adults.
AB  - Sex differences have been observed in neurobehavioral measures and in
      neuroanatomic studies. Men and women differ in emotion processing, including
      perception, experience and expression, most notably reflected in greater male
      aggression. We examine temporo-limbic and prefrontal structures volumetrically in
      a large well-characterized sample of healthy adults, applying morphometric
      methods across cerebral regions that regulate emotions. Quantitative magnetic
      resonance imaging (MRI) was performed in 116 healthy adults, 57 men and 59 women,
      age range 18-49 years. We used reliable methods of region of interest
      identification to examine sex differences in volume of temporo-limbic and frontal
      regions. An automated tissue segmentation procedure was used to obtain separate
      measurements for gray and white matter. After correcting for cranial volume, men
      and women had identical volumes of amygdala and hippocampus, as well as dorsal
      prefrontal cortex. However, women had larger orbital frontal cortices than men,
      resulting in highly significant difference in the ratio of orbital gray to
      amygdala volume (P = 0.002). The larger volume of cortex devoted to emotional
      modulation may relate to behavioral evidence for sex differences in emotion
      processing.

PMID- 12183400
TI  - hCDC4 gene mutations in endometrial cancer.
AB  - Cyclin-dependent kinase 2 activated by cyclin E is involved in the initiation of
      DNA replication and other S phase functions. Consistent with this role, cyclin E
      protein accumulates at the G1-S phase transition and declines during early S
      phase. This profile of expression is the result of periodic transcription and
      ubiquitin-mediated proteolysis directed by SCF(hCdc4). However, in many types of
      human tumors cyclin E protein is elevated and deregulated relative to the cell
      cycle by an unknown mechanism. Here, we show that the F-box protein hCdc4 that
      targets cyclin E to the SCF (Skp1-Cull-F-box) protein ubiquitin ligase is mutated
      in at least 16% of human endometrial tumors. Mutations were found either in the
      substrate-binding domain of the protein or at the amino terminus, suggesting a
      critical role for the region of hCdc4 upstream of the F-box. hCDC4 gene mutations
      were accompanied by loss of heterozygosity and correlated with aggressive
      disease. The hCDC4 gene is localized to chromosome region 4q32, which is deleted
      in over 30% of human tumors. Our results show that the hCDC4 gene is mutated in
      primary human tumors and suggest that it may function as a tumor suppressor in
      the genesis of many human cancers.

PMID- 12183401
TI  - Cellular and molecular targets of estrogen in normal human breast tissue.
AB  - To gain insight into the in vivo role of estrogen, we isolated estrogen receptor
      positive cells fromnormal human breast tissue using a recombinant adenovirus that
      expresses green fluorescence protein in response to estrogen. We compared the
      global gene expression profile of these estrogen receptor-positive cells with
      that of various normal and cancerous mammary epithelial cells and identified
      several genes not implicated previously in estrogen signaling. One of these
      genes, lipocalin 2, is a putative in vivo estrogen target gene and paracrine
      factor that mediates the growth regulatory effects of estrogen in normal breast
      epithelium. These results demonstrate that normal and cancerous estrogen receptor
      positive cells are distinct at the molecular level and suggest that lipocalin 2
      is a new therapeutic target for breast cancer prevention and treatment.

PMID- 12183402
TI  - The kinetics of deregulation of expression by de novo methylation of the h19
      imprinting control region in cancer cells.
AB  - Epigenetic lesions are common in neoplasia and range from hypermethylation of
      subsets of CpG islands to loss of imprinting. By exploiting an episomal model
      system and the strong de novo methylation capacity of a human cancer cell line,
      we show that an H19 minigene rapidly becomes methylated and silenced, mimicking
      the inactivation of the maternal H19 allele in a range of cancers. Although the
      H19 imprinting control region (ICR) initially displayed methylation protection,
      it eventually succumbed to the pressure mounted by the de novo methylation
      machinery of the JEG-3 cells. Importantly, we were able to visualize the kinetics
      of the loss of the H19 ICR chromatin insulator function in association with
      chromatin compaction. Our results document that a strong de novo methylation
      machinery leads to loss of methylation privilege states of H19 ICR to
      functionally manifest loss of insulator function in a matter of only a few days
      in human cancer cells.

PMID- 12183403
TI  - Hepatocellular carcinoma caused by loss of heterozygosity in Lkb1 gene knockout
      mice.
AB  - Germline mutations of the LKB1 gene are associated with Peutz-Jeghers syndrome,
      which is characterized by mucocutaneous pigmentation and gastrointestinal
      hamartoma with an increased risk of cancer development. To investigate the role
      of LKB1 in vivo, we have recently constructed Lkb1 gene knockout mice. Because of
      Lkb1 gene haploinsufficiency, the heterozygous Lkb1 mice develop gastrointestinal
      polyps of which the histological characteristics resemble those of the Peutz
      Jeghers syndrome hamartomas. Here we demonstrate that the Lkb1 (+/-) mice develop
      hepatocellular carcinomas (HCCs). In Lkb1 (+/-) mice >50 weeks of age, >70% of
      the male mice developed HCCs, whereas only 20% of the females had HCCs, showing a
      sex difference in the susceptibility. Histological examinations revealed various
      types of HCCs, such as "trabecular," "clear cell," "pseudoglandular," and
      "sarcomatous" types, which were strikingly similar to those found in human HCCs.
      Western blotting and PCR analyses showed loss of Lkb1 heterozygosity in all of
      the HCC tissues examined, indicating a tumor suppressor role of LKB1 in the mouse
      liver. These results suggest that lack of LKB1 is a novel mechanism for HCC
      development. Thus, the Lkb1 (+/-) knockout mutant should be an important and
      useful model for human HCC.

PMID- 12183404
TI  - Few FH mutations in sporadic counterparts of tumor types observed in hereditary
      leiomyomatosis and renal cell cancer families.
AB  - Loss of function mutations in the fumarate hydratase (fumarase, FH) gene were
      recently identified as the cause for dominantly inherited uterine and cutaneous
      leiomyomas and renal cell cancer. To further evaluate the role of FH in
      tumorigenesis, we screened FH mutations from tumor types seen in hereditary
      leiomyomatosis and renal cell cancer mutation carriers-41 uterine and 10
      cutaneous leiomyomas, 52 renal cell carcinomas, 53 sarcomas, 29 prostate
      carcinomas, and 15 lobular breast carcinomas. Few mutations were detected.
      Biallelic inactivation of FH was found in one uterine leiomyosarcoma, one
      cutaneous leiomyoma, and one soft tissue sarcoma. Whereas the two former lesions
      were shown to originate from a germ-line mutation, the soft tissue sarcoma is to
      our knowledge the first example of purely somatic inactivation of FH in tumors.

PMID- 12183405
TI  - No effects of Smad2 (madh2) null mutation on malignant progression of intestinal
      polyps in Apc(delta716) knockout mice.
AB  - The loss of heterozygosity (LOH) in human chromosome 18q21 is found at high
      frequencies in advanced pancreatic and colorectal cancers. Several candidate
      tumor suppressor genes, such as SMAD2, SMAD4, and DCC, are located in this
      region. The homologues of these genes in the mouse are also clustered on
      chromosome 18. Mutations in the adenomatous polyposis coli (APC) gene are
      responsible for familial adenomatous polyposis, and we earlier constructed a
      mouse model for familial adenomatous polyposis, Apc(delta716). Although human APC
      is located on chromosome 5q, mouse Apc is on chromosome 18, 30 cM proximal to the
      Dcc-Smad4-Smad2 locus. Taking advantage of this fact, we constructed previously a
      cis-compound Apc(delta716) Smad4 mutant, the intestinal polyps of which progress
      to very invasive adenocarcinomas. To determine whether Smad2 mutations play
      similar roles in malignant progression, here we constructed compound mutant mice
      carrying Apc and Smad2 knockouts in the cis configuration. In contrast to the cis
      compound Apc(delta716) Smad4 heterozygotes, the polyps in the cis-compound
      Apc(delta716) Smad2 heterozygotes showed no difference in the number, size, or
      histopathology from the polyps in the simple Apc(delta716) heterozygotes. These
      results suggest that, on human chromosome 18q21, the SMAD4 LOH plays a more
      significant role, and SMAD2 LOH is insufficient to cause malignant progression of
      colonic polyps.

PMID- 12183408
TI  - Novel NUP98-HOXC11 fusion gene resulted from a chromosomal break within exon 1 of
      HOXC11 in acute myeloid leukemia with t(11;12)(p15;q13).
AB  - The NUP98 gene has been reported to be fused to 11 partner genes in hematological
      malignancies with 11p15 translocations. Among NUP98 fusion partner genes, HOXA
      and HOXD clusters have been reported thus far; however, no HOXC or HOXB clusters
      have been reported. We identified a novel NUP98-HOXC11 fusion gene in a pediatric
      patient with de novo acute myeloid leukemia having t(11;12)(p15;q13). The
      breakpoint of NUP98 was located within a LINE repetitive sequence (HAL1) in
      intron 12, and the breakpoint of HOXC11 was located within exon 1, resulting in a
      NUP98-HOXC11 in-frame fusion transcript containing exon 12 of NUP98 fused to a
      part of exon 1 of HOXC11 with an 8-bp insertion derived from the intron sequence
      just 5' of the breakpoint of NUP98. The NUP98-HOXC11 fusion protein consists of
      the NH2-terminal phenylalanine-glycine repeat motif of NUP98 and the COOH
      terminal homeodomain of HOXC11. Although the frequency of HOXC11 expression was
      not high in leukemia cell lines, its expression was significantly more frequent
      in myeloid than lymphoid leukemia cell lines. These data suggest that the NUP98
      HOXC11 fusion protein plays a role in the pathogenesis of myeloid malignancies.

PMID- 12183406
TI  - Cyclin D1 is not an essential target of beta-catenin signaling during intestinal
      tumorigenesis, but it may act as a modifier of disease severity in multiple
      intestinal neoplasia (Min) mice.
AB  - Deregulation of beta-catenin activity is an important step in the development of
      colorectal cancers. One consequence of this is transcriptional activation of
      cyclin D1, an oncogene known to be overexpressed in colorectal cancers. We tested
      the hypothesis that cyclin D1 gene activation is important for intestinal
      tumorigenesis. Multiple intestinal neoplasia mice (a model for human familial
      adenomatous polyposis) were crossed with cyclin D1 knockout (Ccnd1(-/-)) mice.
      Despite the absence of cyclin D1, intestinal tumors still developed. However,
      Ccnd1(-/-) multiple intestinal neoplasia mice developed significantly fewer
      tumors than Ccnd1(+/-) or Ccnd1(+/+) mice (P = 0.003). We conclude that cyclin D1
      is not essential for intestinal tumorigenesis, but it may act as a modifier gene.

PMID- 12183407
TI  - Genetic and environmental determinants on tissue response to in vitro carcinogen
      exposure and risk of breast cancer.
AB  - To test the hypothesis that individual susceptibility to carcinogen exposure is a
      risk factor for breast cancer, we measured DNA adduct formation in normal breast
      tissues treated in vitro with 4 micro M benzo(a)pyrene in 76 cancer cases and 60
      noncancer controls. We found a significantly higher level of adducts (134.6 +/-
      21.2/10(9)) among cases compared with controls (66.9 +/- 7.5; P = 0.007). The
      level of adducts was significantly associated with the risk of breast cancer
      (odds ratio, 4.38; 95% confidence interval, 1.04 to 18.50; P = 0.044) after
      adjusting for confounders. Stratified analysis and regression analysis
      demonstrated that race, pack-years of smoking, family history of breast cancer,
      and CYP1B1 genotype were significant predictors of the level of benzo(a)pyrene
      induced adducts in the breast tissues. These observations suggest that genetic
      susceptibility to carcinogen exposure may play an important role in breast
      carcinogenesis.

PMID- 12183409
TI  - Telomerase is regulated by c-Jun NH2-terminal kinase in ovarian surface
      epithelial cells.
AB  - Telomerase activity is present in >90% of all tumors and appears to be regulated
      by the phosphatidylinositol 3-kinase signaling pathway. Here we demonstrate that
      Akt is not involved in the signaling cascade for telomerase regulation in ovarian
      surface epithelial cells. However, we showed that c-Jun NH2-kinase induces
      telomerase activity, that inhibition of JNK by JIP abrogates telomerase activity,
      and that JNK expression activates transcription of a reporter gene fused to the
      hTERT promoter sequence. Consequently, our data show that JNK is a key regulator
      of telomerase activity and, hence, may provide new perspectives on tumorigenesis
      that could be exploited for novel therapeutic strategies.

PMID- 12183410
TI  - Allele separation facilitates interpretation of potential splicing alterations
      and genomic rearrangements.
AB  - Mutations that alter normal splice patterns and genomic rearrangements are common
      causes of hereditary diseases including hereditary nonpolyposis colorectal
      cancer. However, abnormal transcripts can be difficult to detect and interpret
      because splicing patterns are often heterogeneous even in normal cells. Standard
      techniques including sequencing and Southern hybridization fail to detect some
      genomic rearrangements. We show here that separation of alleles in somatic cell
      hybrids, through "conversion" technology, considerably facilitates the
      interpretation of abnormal splicing patterns and the detection of genomic
      rearrangements. We detected novel mutations in MLH1 in each of four hereditary
      nonpolyposis colorectal cancer patients. The genomic mutations were CAG>CAA
      predicting Q346Q; GAG>AAG predicting E102K; a>g at nucleotide 1559-2 at intron
      13, and a tandem duplication involving exons 7-12. By separating the two alleles,
      we showed that one allele produced only abnormal transcript or no transcript
      whereas the other allele produced only normal transcript. These results allowed
      pathogenicity to be unambiguously assigned to the mutations and increased the
      sensitivity of genomic testing.

PMID- 12183411
TI  - Interaction of the EWS NH2 terminus with BARD1 links the Ewing's sarcoma gene to
      a common tumor suppressor pathway.
AB  - In 85% of Ewing family tumors, the NH2 terminus of EWS is fused to the DNA
      binding domain of FLI1, an ets transcription factor. The resulting chimeric
      protein is a strong transcriptional activator with transforming activity. We
      report that EWS and EWS-FLI1 interact via their common NH2 terminus with the COOH
      terminus of BARD1, a putative tumor suppressor, in vitro and in vivo. Because
      BARD1 associates via its NH2-terminal RING domain with the breast cancer
      susceptibility gene BRCA1 that provides a platform for interactions with proteins
      involved in DNA repair and checkpoint control, our results provide a link between
      the Ewing's sarcoma gene product and the genome surveillance complex.

PMID- 12183413
TI  - Doxorubicin treatment in vivo causes cytochrome C release and cardiomyocyte
      apoptosis, as well as increased mitochondrial efficiency, superoxide dismutase
      activity, and Bcl-2:Bax ratio.
AB  - There have been very few investigations as to whether mitochondrial-mediated
      apoptosis in vivo is the underlying mechanism of doxorubicin cardiotoxicity.
      Moreover, no investigations have been conducted to determine whether there are
      adaptive responses after doxorubicin treatment. We administered a single dose of
      doxorubicin (20 mg/kg) to male rats and isolated intact mitochondria from their
      hearts 4 days later. Apoptosis, as determined by the amount of cytosolic
      mononucleosomal and oligonucleosomal DNA fragments (180 bp or multiples), was
      significantly increased after doxorubicin treatment. In contrast, Troponin-T, a
      cardiac-specific marker for necrotic damage, was unaltered 4 days after
      doxorubicin treatment. Cytosolic cytochrome c increased 2-fold in the doxorubicin
      treated rats and was significantly correlated (r = 0.88; P < 0.01) with the
      increase in caspase-3 activity observed. Moreover, the level of bleomyocin
      detectable iron in serum was significantly increased and may have contributed to
      the increase in oxidative stress, which was indicated by an increase in cytosolic
      8-iso prostaglandin F(2alpha). Cytosolic copper zinc superoxide dismutase
      activity also increased significantly further supporting the notion that
      doxorubicin increases superoxide radical production. In addition to adaptations
      to antioxidant defenses, other adaptive mechanisms occurred in the mitochondria
      such as an increase in the respiratory P/O ratio and an increase in the Bcl-2:Bax
      ratio. These findings demonstrate that doxorubicin induces oxidative stress and
      mitochondrial-mediated apoptosis, as well as adaptive responses by the
      mitochondria to protect cardiac myocytes in vivo.

PMID- 12183415
TI  - Neoplastic transformation of human lung fibroblast MRC-5 SV2 cells induced by
      benzo[a]pyrene and confluence culture.
AB  - Benzo[a]pyrene (BaP) is potent rodent carcinogen and a reputed human carcinogen.
      Although much is known about its metabolic activation leading to DNA damage, the
      mechanisms of its actions are not as well understood at a cellular level. In
      addressing this, we have established an in vitro model that follows the
      progression toward neoplastic transformation induced by BaP. The model uses
      immortal nontumorigenic human lung fibroblast MRC-5 SV2 cells as effectors,
      cocultured with a metabolically competent human lymphoblastoid line h1A1v2
      (activator cells). Treatment of the coculture with BaP for 48 h induced a dose
      dependent decrease in cloning efficiency of the MRC-5 SV2 cells; nevertheless,
      cultures continued to progress to confluence. At prolonged confluence culture
      (day 11), an elevation in the proportion of G2-M phase cells was detected by flow
      cytometry. By day 15, the G2-M phase peak disappeared, accordant with the
      appearance of a population with DNA content greater than the cells in G2-M phase.
      These changes in DNA ploidy were coincident with changes in morphology,
      specifically the appearance of enlarged and irregular-shaped nuclei. Confluence
      culture of BaP-treated MRC-5 SV2 cells for more than 2 weeks resulted in cell
      death; however, a few colonies survived the crisis to reach confluence again
      after an additional 10-14 days. The number of death-resistant colonies was
      proportional to the dose of BaP, with the majority of the cells exhibiting
      abnormal morphology. The degree of morphological change progressively increased
      with successive rounds of confluence. Cells that survived three rounds of
      confluence adopted a vastly different morphology, becoming polygonal, spindle, or
      other irregular-shaped, and acquired the ability to form large dense clumps that
      grew in an anchorage-independent manner. In parallel experiments, treatment with
      the vehicle alone (DMSO) resulted in substantially less death resistance and
      lower numbers of high-density clumps. Our studies demonstrate that a single pulse
      treatment of human MRC-5 SV2 cells with metabolically activated BaP increased DNA
      ploidy, induced resistance to confluence-initiated cell death and morphological
      change, and was accompanied by substantial changes in growth pattern under
      prolonged confluence culture. The multiple-step nature of this process is
      characteristic of the development of neoplastic disease, and prolonged confluence
      seemed to play a pivotal role in selecting for carcinogen-induced transformants.

PMID- 12183414
TI  - CBFA2T3 (MTG16) is a putative breast tumor suppressor gene from the breast cancer
      loss of heterozygosity region at 16q24.3.
AB  - Numerous cytogenetic and molecular studies of breast cancer have identified
      frequent loss of heterozygosity (LOH) of the long arm of human chromosome 16. On
      the basis of these data, the likely locations of breast cancer tumor suppressor
      genes are bands 16q22.1 and 16q24.3. We have mapped the CBFA2T3 (MTG16) gene,
      previously cloned as a fusion partner of the AML1 protein from a rare (16;21)
      leukemia translocation, to the 16q24.3 breast cancer LOH region. The expression
      of CBFA2T3 was significantly reduced in a number of breast cancer cell lines and
      in primary breast tumors, including early ductal carcinomas in situ, when
      compared with nontransformed breast epithelial cell lines and normal breast
      tissue. Reintroduction of CBFA2T3 into different breast tumor derived cell lines
      with decreased expression of this gene reduced colony growth on plastic and in
      soft agar. CBFA2T3 was shown to function as a transcriptional repressor when
      tethered to the GAL4 DNA-binding domain in a reporter gene assay and, therefore,
      has the potential to be a transcriptional repressor in normal breast epithelial
      cells. Taken together, these findings suggest that CBFA2T3 is a likely candidate
      for the breast cancer tumor suppressor gene that is the target for the frequent
      16q24 LOH in breast neoplasms.

PMID- 12183412
TI  - Phosphorylation of serine 1387 in Brca1 is specifically required for the Atm
      mediated S-phase checkpoint after ionizing irradiation.
AB  - Although it is well established that inheritance of mutations in the Brca1 gene
      significantly increases the chances of developing breast or ovarian cancers, the
      mechanisms underlying this specific tumor susceptibility remain to be clarified.
      It is clear that one of the roles of the Brca1 protein is to facilitate cellular
      responses to DNA damage. We recently reported that Brca1 function is required for
      appropriate cell cycle arrests after ionizing irradiation in both the S-phase and
      the G2 phase of the cell cycle. We also found that mutation of serine 1423 in
      Brca1, a target of Atm phosphorylation, abrogates the G2-M checkpoint but not the
      ionizing irradiation-induced S-phase checkpoint. Here we demonstrate that
      mutation of serine 1387 in Brca1, another target of Atm phosphorylation,
      conversely abrogates the radiation-induced S-phase arrest but does not affect the
      G2-M checkpoint. Thus, these two posttranslational modifications of Brca1 have
      two distinct functional roles in the protein. In addition, although mutation of
      this site abrogates the ionizing irradiation-induced S-phase arrest, it does not
      adversely affect cell survival after irradiation. This demonstrates that loss of
      this checkpoint function by itself does not affect cell survival and suggests
      that some other function of Brca1 alters cell survival after DNA damage.

PMID- 12183416
TI  - Modulation of epidermal tumor development caused by targeted overexpression of
      epidermis-type 12S-lipoxygenase.
AB  - In contrast to other 12S-lipoxygenase (LOX) isoforms expressed in the skin of
      mice, epidermis-type (e) 12S-LOX was found to be transcriptionally down-regulated
      in the course of epidermal tumor development in NMRI mice. This may indicate that
      this enzyme is related to antitumorigenic rather than protumorigenic effects. To
      test this hypothesis, two transgenic mouse lines were generated that
      differentially expressed e12S-LOX under the control of the bovine keratin 6
      promoter known to be constitutively up-regulated in mouse skin tumors. As
      compared with the wild-type, low transgene expression correlated with a decreased
      skin tumor response paralleled by an up-regulation of leukocyte-type 12S-LOX and
      an accumulation of the linoleic acid derivative 13S-hydroxyoctadecadienoic acid.
      In contrast, high transgene expression coincided with an increased tumor response
      paralleled by a strong keratin 6 promoter-driven up-regulation of the transgenic
      e12S-LOX and an accumulation of the arachidonic acid derivative 12S
      hydroxyeicosatetraenoic acid as the predominant LOX product. These results
      indicate a complex interaction between different LOX isoforms and an opposite
      role of arachidonic acid and linoleic acid products in the modulation of skin
      carcinogenesis.

PMID- 12183417
TI  - Enhanced benefit from adjuvant chemotherapy in breast cancer patients classified
      high-risk according to urokinase-type plasminogen activator (uPA) and plasminogen
      activator inhibitor type 1 (n = 3424).
AB  - Risk assessment and prediction of response to treatment are prerequisites for
      individualized adjuvant therapy decisions in breast cancer. The strong prognostic
      impact of the two invasion factors urokinase-type plasminogen activator (uPA) and
      its inhibitor, plasminogen activator inhibitor type 1 (PAI-1), in breast cancer
      has recently been validated at level-I evidence. This article considers the
      predictive impact of uPA/PAI-1 on response to adjuvant chemo- and endocrine
      therapy in 3424 primary breast cancer patients from two different data sets. uPA
      and PAI-1 antigen levels were measured by ELISA in primary tumor tissue extracts.
      After a median follow-up of 83 months, uPA/PAI-1 has a significant impact on
      disease-free survival in Cox multivariate analysis (P < 0.001; hazard ratio, 2.0;
      95% confidence interval, 1.8-2.3). Patients with high uPA/PAI-1 levels benefit
      more strongly from adjuvant chemotherapy than those with low levels. This effect
      is seen as a significant interaction between chemotherapy and uPA/PAI-1 for the
      entire collective (P < 0.003; hazard ratio, 0.68; 95% confidence interval, 0.53
      0.88) and separately within nodal subgroups. This enhanced benefit in the high
      uPA/PAI-1 patients occurs over and above the significant impact of both therapies
      in all patients. We find no corresponding significant interaction between
      endocrine therapy and uPA/PAI-1; i.e., no significant difference in benefit
      between patients with high and low uPA/PAI-1. In conclusion, uPA and PAI-1 levels
      in primary tumor tissue provide clinically relevant information on relapse risk
      and treatment response that will help to tailor adjuvant therapy concepts in
      breast cancer, accounting for individual biological tumor characteristics.

PMID- 12183418
TI  - Oxytocin synthesis and oxytocin receptor expression by cell lines of human small
      cell carcinoma of the lung stimulate tumor growth through autocrine/paracrine
      signaling.
AB  - The objective of the present work was to investigate the existence of an oxytocin
      (OT)-mediated autocrine/paracrine signaling upon small cell carcinoma of the lung
      (SCCL) cell growth. In that view, OT receptor (OTR) expression, concomitant with
      OT synthesis and secretion, was evidenced on three different SCCL cell lines
      (DMS79, H146, and H345) and related to the vasopressin (VP) system. Specific OT,
      VP, OTR, V1a VP receptor (V1aR), and V1b/V3 VP receptor (V1bR/V3R) transcripts
      were identified by reverse transcription-PCR in all cell lines studied. Binding
      of 125I-(d(CH2)(5)(1), Tyr(Me)(2),Thr(4),Orn(8),Tyr(9)-NH2)-vasotocin (OVTA) was
      observed on all SCCL cell lines, with a K(d) (dissociation constant) ranging from
      0.025-0.089 nM, depending on the cell line and the analytical method. Selectivity
      of 125I-OVTA binding was confirmed by displacement curves obtained with various
      OTR and VP receptor agonists and antagonists (OT, OVTA, L-371,257, VP, F180).
      Immunocytochemistry identified cellular OT and VP, and peptide secretion was
      measured in supernatants of SCCL cultures. [3H]Thymidine incorporations, applied
      on H345 cells, demonstrated a dose-dependent mitogenic effect of exogenous OT (1
      and 100 nM) that was abolished by the OTR antagonist OVTA. A decrease of
      proliferation was also observed with OVTA alone, showing a functional mitogenic
      effect of tumor-derived OT. Taken together, these observations demonstrate the
      existence of a functional OT-mediated autocrine/paracrine signaling actively
      implicated in growth and development of SCCL tumors. Furthermore, these findings
      point to the potential of OT antagonists for development as therapeutic agents
      for the treatment of SCCL.

PMID- 12183419
TI  - A population-based study of the Arg399Gln polymorphism in X-ray repair cross-
      complementing group 1 (XRCC1) and risk of pancreatic adenocarcinoma.
AB  - XRCC1 (X-ray repair cross-complementing group 1) is a base excision repair
      protein that plays a central role in the repair of DNA strand breaks and base
      damage from a variety of endogenous and exogenous oxidants including tobacco
      smoke. One genetic polymorphism (G-->A, Arg-->Gln at codon 399) occurs within a
      poly(ADP-ribose) polymerase binding region and within the central breast cancer
      susceptibility gene 1 product COOH terminus domain of XRCC1. The variant 399Gln
      allele of XRCC1 has been associated with elevated biomarkers of DNA damage in
      human cells. We conducted an analysis of the Arg399Gln polymorphism in XRCC1
      using genomic DNA, and questionnaire information from 309 cases of pancreatic
      adenocarcinoma and 964 controls that were part of a population-based, case
      control study conducted in the San Francisco Bay Area between 1994 and 2001. We
      genotyped individuals using a mass spectrometry-based method. Because smoking and
      obesity are known and suspected pancreas cancer risk factors, and have been
      associated with DNA damage and oxidative stress in target tissues, we estimated
      odds ratios (ORs), interaction contrast ratios (ICRs), and 95% confidence
      intervals for the combined effects of XRCC1 genotype and smoking or body mass
      index (in kg/m(2)). We also assessed potential gene-gene interactions between
      polymorphisms in XRCC1 and CYP1A1, GSTT1, and GSTM1. We found little or no
      evidence for an association between XRCC1 genotype and pancreatic cancer among
      Caucasians, African-Americans, or Asians. There was evidence for interaction
      between XRCC1 399Gln and smoking that was stronger among women than men. Relative
      to never active or passive smokers with the Arg/Arg genotype, the age- and race
      adjusted ORs and ICRs (95% confidence limits) for heavy smoking (>or=41 pack
      years) were: for Gln/Gln or Arg/Gln genotypes [women OR = 7.0 (2.4, 21), ICR =
      3.1 (0.03, 6.2); men OR = 2.4 (1.1, 5.0), ICR = 1.3 (-0.20, 2.8)]; and for the
      Arg/Arg genotype [women OR = 2.2 (0.73, 6.4); men OR = 1.5 (0.68, 3.2)]. Analyses
      of combined genotypes suggested an interaction between XRCC1 (Gln/Gln or Arg/Gln)
      and GSTT1/GSTM1-null/null among women but not among men. There was no evidence of
      interaction between XRCC1 genotype and body mass index. Our results suggest that
      the XRCC1 399Gln allele is a potentially important determinant of susceptibility
      to smoking-induced pancreatic cancer. Our findings, including stronger
      associations and interactions among women, require replication in additional
      study populations.

PMID- 12183420
TI  - The role of adenovirus-mediated retinoblastoma 94 in the treatment of head and
      neck cancer.
AB  - A truncated retinoblastoma (RB) protein of approximately 94 kDa (RB94), lacking
      the NH2 -terminal 112 amino acid residues of the full-length RB, has been found
      to have great efficacy in tumor suppression. This study investigated the role of
      adenovirus-mediated RB94 (Ad-RB94) gene therapy for human head and neck squamous
      cell carcinoma (HNSCC) and explored the cellular and molecular mechanism of tumor
      inhibition after Ad-RB94 gene transfer. Randomized controlled studies in vitro
      and in vivo were performed to assess antitumor responses of Ad-RB94 gene transfer
      against human HNSCC. Human HNSCC cell lines, JHU006 and JHU012, were used in this
      study. Tumors originated from the HNSCC cell lines were propagated as xenografts
      in nude mice. Ad-RB94 gene transfer was performed both in vitro and in vivo with
      replication-defective virus (DL312) and no treatment as controls. Transgene
      expression, cell viability, and tumor growth were evaluated in transfected cells
      and tumor implants. To determine the mechanism behind the observed antitumor
      action, cell cycle analysis was performed, and telomerase activity was examined.
      Tumors were evaluated for RB94-induced apoptosis. Transgene expression of RB94
      was detected by Western blot analysis, real-time quantification reverse
      transcription-PCR, and immunohistochemistry. RB94 expression led to flattening of
      cell growth curves and caused tumor regression. Animals treated with Ad-RB94 were
      seen to have a significant reduction in tumor size when compared with DL312 (P =
      0.02, both cell lines) and to no treatment groups (P = 0.01, both cell lines).
      Cell cycle arrest in the G(2)-M phase and increased levels of apoptosis occurred
      in tumor cells treated with Ad-RB94. In addition, telomerase activity decreased
      significantly and specifically after Ad-RB94 treatment. This study demonstrates
      that Ad-RB94 gene transfer effectively inhibits HNSCC tumor cell growth in vitro
      and in vivo. The unique property of Ad-RB94 gene transfer to arrest HNSCC tumor
      cells in the G2-M phase of the cell cycle makes it a good candidate for adjuvant
      therapy with radiation or chemotherapy, as tumor cells are most sensitive to
      radiation or cytotoxic drug in this cell cycle phase.

PMID- 12183421
TI  - ZD6474 inhibits vascular endothelial growth factor signaling, angiogenesis, and
      tumor growth following oral administration.
AB  - ZD6474 [N-(4-bromo-2-fluorophenyl)-6-methoxy-7-[(1-methylpiperidin-4
      yl)methoxy]quinazolin-4-amine]is a potent, p.o. active, low molecular weight
      inhibitor of kinase insert domain-containing receptor [KDR/vascular endothelial
      growth factor receptor (VEGFR) 2] tyrosine kinase activity (IC(50) = 40 nM). This
      compound has some additional activity versus the tyrosine kinase activity of fms
      like tyrosine kinase 4 (VEGFR3;IC(50) = 110 nM) and epidermal growth factor
      receptor (EGFR/HER1; IC(50) = 500 nM) and yet demonstrates selectivity against a
      range of other tyrosine and serine-threonine kinases. The activity of ZD6474
      versus KDR tyrosine kinase translates into potent inhibition of vascular
      endothelial growth factor-A (VEGF)-stimulated endothelial cell (human umbilical
      vein endothelial cell) proliferation in vitro (IC(50) = 60 nM). Selective
      inhibition of VEGF signaling has been demonstrated in vivo in a growth factor
      induced hypotension model in anesthetized rat: administration of ZD6474 (2.5
      mg/kg, i.v.) reversed a hypotensive change induced by VEGF (by 63%) but did not
      significantly affect that induced by basic fibroblast growth factor. Once-daily
      oral administration of ZD6474 to growing rats for 14 days produced a dose
      dependent increase in the femoro-tibial epiphyseal growth plate zone of
      hypertrophy, which is consistent with inhibition of VEGF signaling and
      angiogenesis in vivo. Administration of 50 mg/kg/day ZD6474 (once-daily, p.o.) to
      athymic mice with intradermally implanted A549 tumor cells also inhibited tumor
      induced neovascularization significantly (63% inhibition after 5 days; P <
      0.001). Oral administration of ZD6474 to athymic mice bearing established (0.15
      0.47 cm(3)), histologically distinct (lung, prostate, breast, ovarian, colon, or
      vulval) human tumor xenografts or after implantation of aggressive syngeneic
      rodent tumors (lung, melanoma) in immunocompetent mice, produced a dose-dependent
      inhibition of tumor growth in all cases. Statistically significant antitumor
      activity was evident in each model with at least 25 mg/kg ZD6474 once daily (P <
      0.05, one-tailed t test). Histological analysis of Calu-6 tumors treated with 50
      mg/kg/day ZD6474 for 24 days showed a significant reduction (>70%) in CD31
      (endothelial cell) staining in nonnecrotic regions. ZD6474 also restrained growth
      of much larger (0.9 cm(3) volume) Calu-6 lung tumor xenografts and induced
      profound regression in established PC-3 prostate tumors of 1.4 cm(3) volume.
      ZD6474 is currently in Phase I clinical development as a once-daily oral therapy
      in patients with advanced cancer.

PMID- 12183422
TI  - Intraperitoneal therapy of ovarian cancer using an engineered measles virus.
AB  - The use of replicating viruses for cancer therapy (virotherapy) holds much
      promise. We reported previously that the live attenuated Edmonston B vaccine
      strain of measles virus (MV-Edm) had antineoplastic efficacy against
      hematological malignancies. In this study, we demonstrate that a recombinant MV
      Edm, genetically engineered to express an inert soluble marker peptide (MV-hCEA),
      is potent against human epithelial ovarian cancer cells in vitro and in vivo. The
      virus was selectively oncolytic for ovarian tumor cells but caused minimal
      cytopathic damage on nontransformed ovarian surface epithelium and mesothelium.
      In contrast to nontransformed cells, the ovarian tumor cells expressed high
      levels of the measles virus receptor CD46. When injected directly into large
      established s.c. SKOV3ip.1 human epithelial ovarian xenografts in athymic mice,
      the virus induced complete regression of 80% of the tumors. i.p. administration
      of virus enhanced the median survival of mice with advanced i.p. SKOV3ip.1 tumors
      by >50 days. In addition, we could easily follow the kinetic profile of viral
      gene expression in the treated mice by determining serum levels of the virally
      encoded marker peptide (soluble human carcinoembryonic antigen). Trackable
      recombinant measles viruses warrant further investigation for therapy of ovarian
      cancer.

PMID- 12183423
TI  - Novel oncolytic adenoviruses targeted to melanoma: specific viral replication and
      cytolysis by expression of E1A mutants from the tyrosinase enhancer/promoter.
AB  - Malignant melanoma is characterized by growing incidence, early metastasis, and a
      lack of effective treatment for advanced disease, suggesting a pressing need for
      novel therapeutic approaches. Conditionally replicative adenoviruses (CRAds)
      constitute a new and promising strategy for cancer treatment that has been
      rapidly translated into clinical trials. We engineered novel melanoma-targeted
      CRAds, AdTyrdelta24 and AdTyrdelta2delta24, by replacing the adenoviral E1A
      promoter with a cassette containing a polyA sequence and a human tyrosinase
      enhancer/promoter construct (hTyr2E/P). The small size of this cassette allows
      retention of the E3 region within these CRAds, which was shown to enhance viral
      spread and oncolysis. In addition, we introduced mutations (delta24 and
      delta2delta24) into the viral E1A gene, which attenuate adenoviral replication in
      quiescent cells. The cell cycle pathways mediating this attenuation are defective
      in melanoma cells. By analysis of E1A expression, we prove fidelity of hTyr2E/P
      in the adenoviral genome and in the context of viral replication when an upstream
      polyA was included. We further show efficient cytotoxicity of AdTyrdelta24 and
      AdTyrdelta2delta24 in melanoma cell lines and a 100-1000-fold attenuation in cell
      lines derived from various nonmelanocytic tissues. Virus replication and progeny
      production of these viruses were similarly selective, resulting in 200-800-fold
      higher virus yields in melanoma cells versus control cells, thus establishing
      viral cytolysis and spread as the cause of the observed cell killing.
      Cytotoxicity of AdTyrdelta24 for normal fibroblasts and keratinocytes was
      strongly attenuated, and this virus caused selective killing of melanoma cells
      but not surrounding keratinocytes in a coculture system. Progeny production and
      cytotoxicity of AdTyrdelta24 in melanoma cells were similar to matching viruses
      containing the stronger cytomegalovirus enhancer/promoter instead of hTyr2E/P.
      Furthermore, AdTyrdelta24 showed a cytopathic effect similar to the wild-type E1A
      containing AdTyrwt and only minimally reduced compared with wild-type adenovirus.
      We conclude that the generated CRAds AdTyrdelta24 and AdTyrdelta2delta24
      constitute novel targeted agents for gene therapy and viral oncolysis of
      metastatic melanoma.

PMID- 12183425
TI  - An antiangiogenic urokinase-derived peptide combined with tamoxifen decreases
      tumor growth and metastasis in a syngeneic model of breast cancer.
AB  - Expression of urokinase (uPA) and its receptor (uPAR) is associated with
      increased tumor-cellinvasion and metastasis in several malignancies including
      breast cancer. An 8-mer peptide derived from the nonreceptor-binding domain of
      urokinase (A6) has been shown to have antiangiogenic and proapoptotic effects to
      block the progression of breast cancer in vivo. In the present study, we
      evaluated the effects of A6 and the antiestrogen tamoxifen (TAM) alone and in
      combination on estrogen-receptor-positive Mat B-III rat breast cancer cells in
      vitro and in vivo. Treatment of Mat B-III cells with A6 and TAM resulted in a
      dose-dependent decrease in tumor-cell invasion through Matrigel; these effects
      were more marked when A6 and TAM were tested in combination. In addition,
      treatment of Mat B-III cells with either A6 or TAM resulted in a significant
      reduction of vascular endothelial growth factor receptor (flk-1) expression and
      in transforming growth factor beta activity, effects that were significantly
      higher after combined treatment with A6 and TAM. For in vivo studies, female
      Fischer rats were inoculated with Mat B-III cells (1 x 10(6)) into the mammary
      fat pad. These orthotopic tumors were staged to 30-40 mm(3) in volume and then
      treatment was initiated with A6 (75 mg/kg/day) and TAM (3 mg/kg/day) alone or in
      combination. Both A6 and TAM caused a significant reduction in tumor volume;
      however, these antitumor effects were significantly greater in animals receiving
      both A6 and TAM, which demonstrated a 75% reduction in tumor growth as compared
      with control animals. The number of macroscopic tumor foci was significantly
      reduced in A6-treated animals, whereas TAM failed to exhibit any antimetastatic
      effects. Histological analysis of primary tumors from different groups showed a
      decrease in new blood-vessel density and increased tumor-cell death in A6- and
      TAM-treated animals, and these effects were greater in experimental animals
      receiving A6 and TAM in combination. Collectively, these studies demonstrate that
      the addition of novel antiangiogenic/antimetastatic agents like A6 to hormone
      therapy can enhance the antitumor effects of hormone therapy through increased
      inhibition of angiogenesis and induction of tumor-cell death.

PMID- 12183426
TI  - Treatment of cancer cells with methioninase produces DNA hypomethylation and
      increases DNA synthesis.
AB  - Methionine depletion in the human cell line CCRF-CEM through the action of
      recombinant methioninase (rMETase), a methionine-cleaving enzyme, was previously
      demonstrated to produce a strong cytotoxic synergistic effect with fluorouracil
      (FUra) throughout a broad range of concentrations of FUra and rMETase, including
      subcytotoxic levels of rMETase. Potentiation was associated with a decrease in
      free thymidylate synthase from preexisting levels. To further investigate the
      action of rMETase on CCRF-CEM cells, in the present study we explored the effects
      of rMETase as a single agent on DNA methylation levels and DNA synthesis, which
      may be changed as a result of deprivation of methionine. Cells treated with
      rMETase under subcytotoxic conditions contained significantly lower levels of
      genomic methylated DNA than did control cells, as demonstrated by incorporation
      of the methyl radical of [methyl-(3)H]S-adenosylmethionine in DNA and by use of
      methylation-sensitive arbitrarily primed PCR. DNA hypomethylation produced by
      rMETase was of similar magnitude as that produced with the DNA methyltransferase
      inhibitor 5-azacytidine. Cells exposed to rMETase synthesized significantly more
      DNA than did untreated cells. Incorporation of [6-3H]thymidine and [6-3H]2'
      deoxyuridine in these cells was augmented over that in control by mean factors of
      1.78 and 2.36, respectively. Increased 3H nucleoside incorporation resulted in
      greater numbers of nuclear grains as demonstrated by autoradiography. The
      increase in DNA synthesis induced by rMETase is likely to result from enhancement
      of DNA repair because it was not accompanied by differences in cell cycle phase
      distribution or in total DNA content as determined by flow cytometry. We
      hypothesize that potentiation of FUra cytotoxicity by rMETase may result from
      increased inhibition of thymidylate synthase, together with DNA hypomethylation
      and enhanced DNA repair that could be involved in cell responses to drug-induced
      damage.

PMID- 12183424
TI  - Phosphatidylinositol 3-kinase/Akt signaling in the response of vascular
      endothelium to ionizing radiation.
AB  - Growth factor enhancement of endothelial cell viability occurs through
      phosphatidylinositol 3-kinase (PI3K)/Akt-mediated inhibition of apoptosis. The
      PI3K/Akt signal transduction pathway was activated by both vascular endothelial
      growth factor and ionizing radiation. Radiation- and vascular endothelial growth
      factor-induced phosphorylation of Akt was inhibited by PI3K antagonists. To
      determine whether this signal transduction pathway represents a therapeutic
      target in tumor vascular endothelium, we examined the effects of the PI3K
      inhibitors wortmannin and LY294002 on irradiated endothelium. Wortmannin and
      LY294002 enhanced radiation-induced apoptosis and cytotoxicity in endothelial
      cells. Tumor vascular window and Doppler ultrasound showed that PI3K antagonists
      enhanced radiation-induced destruction of tumor blood vessels. Tumor growth delay
      was significantly increased after treatment with LY294002 followed by irradiation
      as compared with either agent alone. PI3K in tumor vascular endothelium is a
      potential therapeutic target to enhance the efficacy of ionizing radiation.

PMID- 12183427
TI  - Antitumor activity of a recombinant soluble betaglycan in human breast cancer
      xenograft.
AB  - We have demonstrated previously that ectopic expression of a soluble betaglycan,
      also known as transforming growth factor (TGF) beta type III receptor, can
      suppress the malignant properties of human carcinoma cells by antagonizing the
      tumor-promoting activity of TGF-beta (A. Bandyopadhyay et al., Cancer Res., 59:
      5041-5046, 1999). In the current study, we investigated the potential therapeutic
      utility of a recombinant preparation of human and rat soluble betaglycan (sBG).
      Purified recombinant human sBG showed similar properties to its rat counterpart
      (M. M. Vilchis-Landeros et al., Biochem J., 355: 215-222, 2001). It bound TGF
      beta with high affinity and isoform selectivity and neutralized the activity of
      TGF-beta(1) in two bioassays. Peritumoral (50 micro g/tumor, twice a week) or
      i.p. (100 micro g/animal, every alternate day) injection of sBG into human breast
      carcinoma MDA-MB-231 xenograft-bearing athymic nude mice significantly inhibited
      the tumor growth. The administration of sBG also reduced metastatic incidence and
      colonies in the lungs. The tumor-inhibitory activity of sBG was found to be
      associated with the inhibition of angiogenesis. Systemic sBG treatment
      significantly reduced tumor microvessel density detected with histological
      analyses and CD-31 immunostainings, as well as tumor blood volume measured with
      hemoglobin content. In an in vitro angiogenesis assay, treatment with the
      recombinant sBG significantly reduced the ability of human dermal microvascular
      endothelial cells to form a capillary tube-like structure on Matrigel. These
      findings support the conclusion that sBG treatment suppresses tumor growth and
      metastasis, at least in part by inhibiting angiogenesis. As such, it could be a
      useful therapeutic agent to antagonize the tumor-promoting activity of TGF-beta.

PMID- 12183428
TI  - The role of IFN-gamma in rejection of established tumors by IL-12 : source of
      production and target.
AB  - We have demonstrated previously that established small and large murine MCA207
      sarcomas can be completely eradicated by treatment with interleukin (IL) 12 alone
      and cyclophosphamide plus IL-12 (Cy+IL-12), respectively. The antitumor effect of
      IL-12/Cy+IL-12 has been found to be dependent on IFN-gamma and T cells. The role
      of IFN-gamma in IL-12-induced tumor rejection is unclear, because after IL-12
      administration IFN-gamma is produced by multiple cell types, and it acts on most
      cell types because of the ubiquitous expression of its receptor. Using a T-cell
      adoptive transfer model, we show that after IL-12 treatment, tumor-specific T
      cell production of IFN-gamma is necessary and sufficient for rejection of
      established tumors. Furthermore, by testing tumors using IFN-gamma-unresponsive
      tumor cells, we show that tumor cell expression of MHC class I molecules in vivo
      is abrogated by blocking the response to IFN-gamma. However, tumor response to
      IFN-gamma is not essential for rejection of established small and large tumors by
      IL-12 and Cy+IL-12, respectively; neither is it essential for expression of tumor
      immunogenicity. Our results indicate that the rejection of established tumors by
      IL-12/Cy+IL-12 is dependent on the induction of a Th1 response producing IFN
      gamma that acts on host cells.

PMID- 12183429
TI  - Genetic heterogeneity in the alveolar rhabdomyosarcoma subset without typical
      gene fusions.
AB  - Previous studies of the PAX3-FKHR and PAX7-FKHR gene fusions in alveolar
      rhabdomyosarcoma (ARMS) indicated that the corresponding fusiontranscripts are
      not detectable in 20% of ARMS cases. To investigate the genetic features of this
      ARMS subset, we identified 23 ARMS cases in which PAX3-FKHR and PAX7-FKHR
      transcripts were not detected by a standard sensitivity reverse transcription-PCR
      (RT-PCR) assay. Subsequent analysis with a high sensitivity RT-PCR assay
      identified low-level expression of PAX3-FKHR or PAX7-FKHR in three cases.
      Analysis with a Southern blot assay for PAX3 and PAX7 rearrangements and a
      fluorescence in situ hybridization assay for FKHR rearrangements identified three
      cases with variant fusions in which PAX3 or PAX7 is postulated to be joined to
      novel genomic loci. In one such case, RT-PCR analysis of candidate partners
      identified a fusion of PAX3 to AFX, which is highly similar in structure and
      function to FKHR. Additional fluorescence in situ hybridization analysis
      identified two cases in which a PAX3-FKHR or PAX7-FKHR genomic fusion is present
      but is not associated with a fusion transcript detectable by RT-PCR. Finally, our
      analyses of the PAX3, PAX7, and FKHR loci did not identify rearrangements in >50%
      of cases, consistent with the possibility that there is a true fusion-negative
      subset. In summary, our analysis of ARMS cases without characteristic PAX3-FKHR
      or PAX7-FKHR transcripts identified several genetically distinct subsets
      including low expression or atypical presentation of standard fusions, variant
      fusions with other genes, and possibly true fusion-negative cases.

PMID- 12183430
TI  - Identify metastasis-associated genes in hepatocellular carcinoma through
      clonality delineation for multinodular tumor.
AB  - Disease recurrence and metastasis are frequently observed in many
      successfullytreated localized cancers, including hepatocellular carcinoma in
      which intrahepatic and extrahepatic recurrence (metastasis) are frequently
      observed after curative resection. The present study aimed at identifying
      metastasis-associated genes through delineation of the clonality for multinodular
      liver cancer. The clonal relationship of 22 tumor foci from six patients was
      investigated by the genome-wide expression profile via cDNA microarray consisting
      of 23,000 genes. Tumor molecular properties including p53 protein overexpression
      and gene mutation, hepatitis B virus integration pattern, and genetic alteration
      examined by comparative genomic hybridization were compared. Results indicated
      that gene expression patterns could serve as the molecular fingerprint for
      clonality identification. Together with the molecular data from p53, hepatitis B
      virus integration and comparative genomic hybridization profiles, tumor nodules
      from five patients were confirmed with clonal relationship, and the expression
      profiles of the primary nodules were compared with their corresponding
      intrahepatic metastatic nodules. A total of 90 clones were found to be correlated
      with intrahepatic metastasis by Student's t test (P < 0.05). With reference to
      the primary tumor, 63 clones (39 known genes and 24 express sequence tags) were
      down-regulated whereas 27 clones (14 known genes and 13 express sequence tags)
      were up-regulated in the metastatic nodules. These metastasis-associated genes
      may provide clues to reveal patients with increased risk of developing
      metastasis, and to identify novel therapeutic targets for the treatment of
      metastasis.

PMID- 12183431
TI  - Gene expression in ovarian cancer reflects both morphology and biological
      behavior, distinguishing clear cell from other poor-prognosis ovarian carcinomas.
AB  - Biologically and clinically meaningful tumor classification schemes have long
      been sought. Some malignant epithelial neoplasms, such as those in the thyroid
      and endometrium, exhibit more than one pattern of differentiation, each
      associated with distinctive clinical features and treatments. In other tissues,
      all carcinomas, regardless of morphological type, are treated as though they
      represent a single disease. To better understand the biological and clinical
      features seen in the four major histological types of ovarian carcinoma (OvCa),
      we analyzed gene expression in 113 ovarian epithelial tumors using
      oligonucleotide microarrays. Global views of the variation in gene expression
      were obtained using PCA. These analyses show that mucinous and clear cell OvCas
      can be readily distinguished from serous OvCas based on their gene expression
      profiles, regardless of tumor stage and grade. In contrast, endometrioid
      adenocarcinomas show significant overlap with other histological types. Although
      high-stage/grade tumors are generally separable from low-stage/grade tumors,
      clear cell OvCa has a molecular signature that distinguishes it from other poor
      prognosis OvCas. Indeed, 73 genes, expressed 2- to 29-fold higher in clear cell
      OvCas compared with each of the other OvCa types, were identified. Collectively,
      the data indicate that gene expression patterns in ovarian adenocarcinomas
      reflect both morphological features and biological behavior. Moreover, these
      studies provide a foundation for the development of new type-specific diagnostic
      strategies and treatments for ovarian cancer.

PMID- 12183432
TI  - The T-lineage-affiliated CD2 gene lies within an open chromatin environment in
      acute promyelocytic leukemia cells.
AB  - The nature of hemopoietic progenitors subject to leukemic transformation in acute
      myeloid leukemia (AML) has not been clearly defined. To address this issue, we
      have used DNase I hypersensitivity assays to study the chromatin structure
      surrounding the T-lineage-affiliated CD2 gene in the acute promyelocytic subtype
      of AML (APL). Upstream and downstream flanking regions of CD2 were found to be
      hypersensitive to DNase I in primary APL blasts, with an identical pattern of
      hypersensitive sites to those detected in cells of T-lineage. All of the sites
      were confirmed to be inaccessible to DNase I in B-lineage leukemia cells. The
      demonstration of T-cell-associated chromatin features in primary APL blasts has
      implications for the origin of APL that may arise in more primitive progenitors
      than previously considered to be the case.

PMID- 12183433
TI  - The Bmi-1 oncogene induces telomerase activity and immortalizes human mammary
      epithelial cells.
AB  - The vast majority of breast cancers are carcinomas that arise from mammary
      epithelial cells (MECs). One of the key early events in tumorigenic
      transformation is the ability of cells to overcome replicative senescence.
      However, the precise genetic changes that are responsible for this event in MECs
      is largely unknown. Here, we report that Bmi-1, originally identified as a c-Myc
      cooperating oncoprotein, can bypass senescence, extend the replicative life span,
      and immortalize MECs. Furthermore, Bmi-1 was overexpressed in immortal MECs and
      several breast cancer cell lines. Overexpression of Bmi-1 in MECs led to
      activation of human telomerase reverse transcriptase (hTERT) transcription and
      induction of telomerase activity. Telomerase induction by Bmi-1 was an early
      event in the extension of the replicative life span and immortalization. Bmi-1
      was not overexpressed in hTERT-immortalized MECs, suggesting that Bmi-1 functions
      upstream of hTERT. Although, c-Myc has been reported to induce telomerase in
      MECs, Bmi-1 appeared to act independently of c-Myc binding sequences in the hTERT
      promoter. Deletion analysis of the Bmi-1 protein suggested that the RING finger,
      as well as a conserved helix-turn-helix-turn domain, were required for its
      ability to induce telomerase and immortalize MECs. These data suggest that Bmi-1
      regulates telomerase expression in MECs and plays a role in the development of
      human breast cancer.

PMID- 12183434
TI  - Proinflammatory cytokines block growth of breast cancer cells by impairing
      signals from a growth factor receptor.
AB  - Neutralization of endogenous growth factors and administration of exogenous
      bioactive cytokines are two distinct biological antitumor strategies that show
      promise for treatment of cancer patients. In this report, we provide evidence to
      link both strategies as an integrative approach to cancer therapy. We tested the
      hypothesis that proinflammatory cytokines block growth of transformed cells by
      inhibiting key intracellular signaling events after activation of the insulin
      like growth factor-I (IGF-I) tyrosine kinase receptor. IGF-I stimulates DNA
      synthesis in MCF-7 cells by 15-fold. This increase is significantly inhibited by
      TNF (tumor necrosis factor) -alpha at 0.1 ng/ml and is reduced by 80% at 100
      ng/ml. Similarly, both IL (interleukin) -1beta and IL-6 significantly reduce the
      ability of IGF-I to promote DNA synthesis. Flow cytometry confirmed that all
      three of the cytokines inhibit IGF-I-induced DNA synthesis by preventing cells
      from entering the S phase of the cell cycle, leading to G(0)/G(1) arrest.
      Although none of the cytokines alone are cytotoxic to transformed epithelial
      cells in the absence of serum, TNF-alpha significantly inhibits the antiapoptotic
      property of IGF-I in protecting MCF-7 cells from DNA fragmentation. TNF-alpha and
      IL-1beta act by inhibiting the IGF-I receptor from tyrosine phosphorylating
      insulin receptor substrate-1 without affecting tyrosine kinase activity of the
      IGF-IR itself. These data support the novel idea that the major inhibitory
      properties of proinflammatory cytokines on growth of breast cancer cells are
      manifested prominently in the presence of growth factors. These data also
      highlight growth factor receptor adaptor molecules, such as insulin receptor
      substrate-1, rather than the receptors themselves as targets for antitumor
      therapeutic strategies.

PMID- 12183435
TI  - Molecular changes associated with oral dysplasia progression and acquisition of
      immortality: potential for its reversal by 5-azacytidine.
AB  - This study has identified molecular changes characteristic of early oral cancer
      progression. We reported previously that acquisition of the immortal phenotype is
      an early event in oral cancer development (F. McGregor et al., Cancer Res., 57:
      3886-3889, 1997); our current data indicate that about half of oral dysplasia
      cultures are immortal, and this is associated with loss of expression of retinoic
      acid receptor (RAR)-beta and the cell cycle inhibitor p16(ink4a) (p16), p53
      mutations, and increased levels of telomerase/human telomerase reverse
      transcriptase mRNA. In contrast, increased expression of the epidermal growth
      factor receptor, known to be a characteristic of oral cancer, does not occur
      until after the dysplasia stage in squamous cell carcinomas. Acquisition of
      invasive properties as judged by an in vitro Matrigel invasion assay also does
      not occur until the carcinoma stage and is further increased in metastases.
      Interestingly, one atypical mortal dysplasia with a considerably extended life
      span has lost expression of RAR-beta and p16, but it still expresses only wild
      type p53 (albeit at a higher level than normal) and has not activated telomerase.
      RAR-beta and/or p16 re-expression can be induced by treatment with 5-aza-2
      deoxycytidine (Aza-C) in some immortal dysplasias, and this has been shown to be
      due to silencing of gene expression by promoter methylation. Aza-C treatment also
      down-regulated telomerase activity and human telomerase reverse transcriptase
      mRNA. Interestingly, with one dysplasia, Aza-C was able to reverse its immortal
      phenotype, as judged by morphological criteria and expression of the senescence
      associated acid beta-galactosidase activity during terminal growth arrest; this
      immortal dysplasia was the only one in which Aza-C treatment not only down
      regulated telomerase activity but also induced re-expression of both RAR-beta and
      p16. The possibility of reversing the immortal phenotype of some dysplasias by
      Aza-C may be of clinical usefulness.

PMID- 12183437
TI  - FOXM1 is a downstream target of Gli1 in basal cell carcinomas.
AB  - Forkhead box (FOX) proteins have been shown to play important roles in regulating
      the expression of genes involved in cell growth, proliferation, differentiation,
      longevity, and transformation. The functional importance of this gene family in
      normal human skin physiology and disease processes is not well understood.
      Activation of Sonic Hedgehog (Shh) signaling plays a key role in the development
      of basal cell carcinomas (BCCs) of the skin in humans. Recent studies have
      established that some FOX genes are downstream targets of Shh signaling. We have
      investigated the role of FOX proteins in transducing Shh effects in human skin by
      using degenerate PCR to identify FOX genes differentially expressed in BCCs. All
      three known FOXM1 isoforms (a, b, and c) were detected in human skin and cultured
      keratinocytes, and the transcriptionally active FOXM1b isoform was found to be up
      regulated in BCCs. Real-time quantitative RT-PCR showed that the increase in
      FOXM1 mRNA levels was specific for BCCs and not a reflection of increased cell
      proliferation in that no up-regulation was seen in squamous cell carcinomas or
      proliferating primary human keratinocyte cultures. Immunostaining studies showed
      intense nuclear and cytoplasmic staining throughout BCC tumor islands and not
      confined to the periphery regions of the tumor where proliferating Ki-67
      immunopositive cells are predominantly localized. Expression of the Shh target
      glioma transcription factor-1 (Gli1) in primary keratinocytes and other cell
      lines caused a significant elevation of FOXM1 mRNA level and transcriptional
      activity, indicating that FOXM1 is a downstream target of Gli1. Our data provide
      the first evidence that activation of Shh signaling via Gli1 is an important
      determinant of FOXM1 expression in mammalian cells. Given the role of FOXM1 in
      cell proliferation, the up-regulation of FOXM1 in BCCs may be one of the
      mechanisms whereby Shh signaling exerts its mitogenic effect on basal
      keratinocytes, leading to the development of this common human cancer.

PMID- 12183436
TI  - Promotion of tumor growth by murine fibroblast activation protein, a serine
      protease, in an animal model.
AB  - Fibroblast activation protein (FAP) is a type II integral membrane glycoprotein
      belonging to the serine protease family. Human FAP is selectively expressed by
      tumor stromal fibroblasts in epithelial carcinomas, but not by epithelial
      carcinoma cells, normal fibroblasts, or other normal tissues. FAP has been shown
      to have both in vitro dipeptidyl peptidase and collagenase activity, but its
      biological function in the tumor microenvironment is unknown. The modeled
      structure of murine FAP consists of a short cytoplasmic tail, a single
      hydrophobic transmembrane region, and a large extracellular domain. A seven
      bladed beta-propeller domain is situated on top of the catalytic triad and may
      serve as a "gate" to selectively filter protein access to the catalytic site.
      HEK293 cells transfected to constitutively express murine FAP, when xenografted
      into scid mice, were 2-4 times more likely to develop s.c. tumors and showed a 10
      40-fold enhancement of tumor growth compared with mock-transfected HEK293 cells.
      Rabbits immunized with recombinant murine FAP developed polyclonal anti-FAP
      antibodies that significantly inhibited murine FAP dipeptidyl peptidase activity
      in vitro. HT-29 xenografts treated with these inhibitory anti-FAP antisera
      exhibited attenuated growth compared with tumors treated with preimmunization
      rabbit antisera. These data demonstrate the ability of FAP to potentiate tumor
      growth in an animal model. Moreover, tumor growth is attenuated by antibodies
      that inhibit the proteolytic activity of FAP. These findings suggest a possible
      therapeutic role for functional inhibition of FAP activity.

PMID- 12183438
TI  - MEK1 signaling mediates transformation and metastasis of EpH4 mammary epithelial
      cells independent of an epithelial to mesenchymal transition.
AB  - Activation of the mitogen-activated protein/extracellular signal-regulated kinase
      kinase (MEK)-mitogen-activated protein kinase (MAPK) pathway is a frequent event
      in tumorigenesis, and analysis of human breast carcinomas demonstrates that 25
      50% of these tumors express elevated levels of activated MAPK1/2. However, a
      direct role for MEK1 in regulating the invasive and metastatic potential of
      mammary epithelial cells remains to be established. To directly address the role
      of constitutive MEK1 signaling in transformation, we have selected the murine
      mammary epithelial cell line, EpH4, as a model system. EpH4 cells expressing
      constitutively activated MEK1 display invasive growth in 3-dimensional collagen
      gels and enhanced motility, and metastatic potential in modified Boyden chamber
      assays. Furthermore, analysis of markers of normal epithelial morphology by
      immunofluorescence revealed reorganization of the actin cytoskeleton, and
      mislocalization of beta-catenin and ZO-1 away from sites of cell-cell contact.
      However, in contrast to expectations, these changes occurred independently of an
      epithelial to mesenchymal transition, a change seen frequently in transformed
      epithelial cells. Moreover, transplantation of EpH4 cells expressing
      constitutively activated MEK1 into the cleared mammary fat pads of immune
      competent hosts rapidly produced tumors that were highly invasive, well
      vascularized, and readily metastasized to distant organs. Gene expression
      profiling was performed to identify the downstream targets of MEK1 signaling.
      Constitutive MEK1 induced the expression of genes involved in proliferation and
      of matrix metalloproteinases, which regulate invasion and metastasis. These
      results demonstrate that constitutively activated MEK1 brings about robust
      tumorigenic changes in murine mammary epithelial cells, and mediates their
      invasiveness and metastasis in vivo without a requirement for epithelial to
      mesenchymal transition.

PMID- 12183440
TI  - Receptor for advanced glycation end products-binding COOH-terminal motif of
      amphoterin inhibits invasive migration and metastasis.
AB  - Amphoterin has been suggested to regulate invasive process extension and cell
      migration in tumor cells and embryonic neurons through binding to receptor for
      advanced glycation end products (RAGE), a multiligand transmembrane receptor
      belonging to the immunoglobulin superfamily. In this study, we identify a COOH
      terminal motif in amphoterin (amino acids 150-183) that is responsible for RAGE
      binding. We show that as a surface-bound ligand, this part of amphoterin is
      sufficient to induce RAGE-dependent process extension, suggesting a role in the
      regulation of cell motility. When applied in solution, the RAGE-binding COOH
      terminal motif of amphoterin efficiently inhibits process extension and
      transendothelial migration of tumor cells. Furthermore, in an in vivo model, the
      corresponding synthetic peptide significantly suppresses formation of lung
      metastases. Taken together, these results suggest that amphoterin binds to RAGE
      through a COOH-terminal motif that can be used as an efficient inhibitor to block
      invasive migration of tumor cells.

PMID- 12183439
TI  - A gene expression profile that defines colon cell maturation in vitro.
AB  - Colonic epithelial cells undergo cell cycle arrest, lineage specific
      differentiation, and apoptosis, as they migrate along the crypt axis toward the
      lumenal surface. The Caco-2 colon carcinoma cell line models many of these
      phenotypic changes, in vitro. We used this model system and cDNA microarray
      analysis to characterize the genetic reprogramming that accompanies colon cell
      differentiation. The analyses revealed extensive yet functionally coordinated
      alterations in gene expression during the differentiation program. Consistent
      with cell differentiation reflecting a more specialized phenotype, the majority
      of changes (70%) were down-regulations of gene expression. Specifically, Caco-2
      cell differentiation was accompanied by the coordinate down-regulation of genes
      involved in cell cycle progression and DNA synthesis, which reflected the
      concomitant reduction in cell proliferation. Simultaneously, genes involved in
      RNA splicing and transport, protein translation, folding, and degradation, were
      coordinately down-regulated, paralleled by a reduction in protein synthesis.
      Conversely, genes involved in xenobiotic and drug metabolism were up-regulated,
      which was linked to increased resistance of differentiated cells to
      chemotherapeutic agents. Increased expression of genes involved in extracellular
      matrix deposition, lipid transport, and lipid metabolism were also evident.
      Underlying these altered profiles of expression, components of signal
      transduction pathways, and several transcription factors were altered in
      expression.

PMID- 12183441
TI  - Prostatic intraepithelial neoplasia in mice with conditional disruption of the
      retinoid X receptor alpha allele in the prostate epithelium.
AB  - Retinoids, which are important regulators of cell growth, differentiation, and
      apoptosis, have been used in treatment or chemoprevention of multiple cancers
      including prostate cancer. To elucidate the mechanism of action of retinoids in
      the context of the prostate, we used the Cre-loxP system to disrupt the retinoid
      X receptor alpha (RXRalpha) gene specifically in the prostatic epithelium of the
      mouse. Evidence for tissue-specific gene inactivation was obtained at DNA, RNA,
      and protein levels. Phenotypic changes in the prostate in the homozygous animals
      of different age groups ranging from 1 to 15 months were investigated.
      Developmentally, prostatic ductal branching appeared to be increased from the
      loss of RXRalpha function. There was also a significant change in the profile of
      secretory proteins in the RXRalpha mutant prostate relative to littermate
      controls with intact RXRalpha allele. Histopathologically, homozygous RXRalpha
      deficient prostates showed multifocal hyperplasia as early as 4 months of age.
      Lesions, which could be described as low-grade prostatic intraepithelial
      neoplasias, were detected after 5 months. Subsequently, beginning at
      approximately 10 months, high-grade prostatic intraepithelial neoplasias
      developed in some animals. The incidences of low-grade prostatic intraepithelial
      neoplasias and high-grade prostatic intraepithelial neoplasias among the animals
      10-15 months of age were 62 and 17%, respectively. The heterozygous mutant mice
      also developed similar prostatic phenotypes but in a delayed manner, implying a
      role of haploinsufficiency. Together, these results indicated for the first time
      that a major component of retinoid action in the prostate is mediated by a
      retinoid receptor, RXRalpha, the inactivation of which in the prostatic
      epithelium leads to the development of preneoplastic lesions.

PMID- 12183442
TI  - Autocrine stimulation by osteopontin contributes to antiapoptotic signalling of
      melanocytes in dermal collagen.
AB  - The growth of melanocytes, the pigment-producing cells of the skin, normally is
      restricted to the epidermis. Transformed melanocytes, which have invaded the
      dermis, however, have gained the ability to grow in this new environment and to
      counteract apoptosis induced by the dermal connective tissue. The expression of
      genes contributing to the survival of melanocytes in the dermal environment,
      therefore, might be involved in melanoma development. Using a differential
      display approach, we identified osteopontin as such a gene. In melanocytes,
      expression of the secreted adhesion protein OPN was up-regulated by the melanoma
      inducing receptor tyrosine kinase Xmrk as well as by the fibroblast growth factor
      receptor, which plays a decisive role in human melanoma. Activation of both
      receptors triggered survival of melanocytes in three-dimensional dermal collagen
      gels. Competition experiments revealed that the presence of OPN in the medium as
      a result of receptor signaling was contributing to these effects. Addition of
      exogenous OPN allowed melanocytes to adhere, spread, and survive in three
      dimensional collagen gels, whereas in the absence of OPN, the cells underwent
      apoptosis. The integrin alpha(v)beta(3) known to be involved in melanoma cell
      survival and growth was identified as an OPN receptor, which points to an OPN
      mediated cross-talk between growth factor receptors and this integrin receptor in
      melanocytes. In summary, we could show that in melanocytes growth factor receptor
      induced secretion of OPN can promote antiapoptotic signaling and mediate
      appropriate interactions with the extracellular matrix in an autocrine way. Our
      findings suggest a new role of growth factor receptors of the family of receptor
      tyrosine kinases in processes associated with melanoma development and
      progression.

PMID- 12183443
TI  - Bombesin stimulates invasion and migration of Isreco1 colon carcinoma cells in a
      Rho-dependent manner.
AB  - The membrane receptor for the neuropeptide bombesin/gastrin-releasing peptide
      (GRP) is expressed by a large fraction of human colorectal carcinoma cells. We
      reported previously a stimulation of cell adhesion and lamellipodia formation by
      the neuropeptide bombesin in the human, bombesin/GRP receptor-expressing, Isreco1
      colorectal cancer cell line (J. C. Saurin et al., Cancer Res., 59: 962-967,
      1999). Using invasion and motility assays, we demonstrate in this report that
      bombesin can both enhance the invasive capacity of Isreco1 cells in a dose
      dependent manner (maximal effect at 1 nM) and stimulate the closure of wounds
      performed on confluent Isreco1 cells. These effects were reversed fully by the
      specific bombesin/GRP receptor antagonist D-Phe(6)-Bn(6-13)OMe used at 1 micro M.
      MMP-9 and urokinase-type plasminogen activator were expressed by Isreco1 cells,
      and bombesin did not significantly alter their level of secretion. Interestingly,
      exoenzyme C3 (10 micro g/ml) decreased cell invasiveness induced by bombesin by
      70% and completely inhibited the migration of Isreco1 cells. Similarly, the Rho
      kinase inhibitor Y-27632 dose-dependently reduced the effect of bombesin on cell
      invasion. Moreover, pull-down assays for GTP-bound RhoA demonstrated that
      bombesin was able to activate the small G-protein in Isreco1 cells. These results
      show that the neuropeptide bombesin is able to modulate invasiveness of Isreco1
      colorectal carcinoma cells in vitro through a Rho-dependent pathway, leading to
      an increase in cell locomotion without a significant effect on tumor-cell
      associated proteolytic activity. These findings indicate that bombesin/GRP
      receptor expression may contribute to the cellular events that are critical for
      invasion/migration of colorectal carcinoma cells.

PMID- 12183444
TI  - Correspondence re: Y. Kiniwa et al., Tumor antigens isolated from a patient with
      vitiligo and T-cell-infiltrated melanoma. Cancer Res., 61: 7900-7907, 2001.

PMID- 12183445
TI  - HLA-G transactivation by cAMP-response element-binding protein (CREB). An
      alternative transactivation pathway to the conserved major histocompatibility
      complex (MHC) class I regulatory routes.
AB  - The expression of HLA-G in extravillous cytotrophoblast cells coincides with a
      general lack of classical major histocompatibility complex (MHC) class I
      expression in this tissue. This differential expression of HLA-G and classical
      HLA class I molecules in trophoblasts suggests a tight transcriptional control of
      MHC class I genes. Transactivation of the classical MHC class I genes is mediated
      by two groups of juxtaposed cis-acting elements that can be viewed as regulatory
      modules. Both modules are divergent in HLA-G, rendering this gene unresponsive to
      NF-kappaB, IRF1, and class II transactivator (CIITA)-mediated induction pathways.
      In this study, we searched for alternative regulatory elements in the 1438-bp HLA
      G promoter region. HLA-G was not responsive to interferon-alpha (IFNalpha),
      IFNbeta, or IFNgamma, despite the presence of an upstream ISRE binding IRF1 in
      vitro. However, the HLA-G promoter contains three CRE/TRE elements with binding
      affinity for CREB/ATF and Fos/Jun proteins both in vitro and in vivo. In
      transient transfection assays, it was shown that HLA-G transactivation is
      regulated by CREB, CREB-binding protein (CBP), and p300. Moreover,
      immunohistochemical analysis demonstrated that HLA-G is co-expressed with CREB
      and CBP in extravillous cytotrophoblasts, revealing the in vivo relevance of this
      transactivation pathway. This implies a unique regulation of HLA-G transcription
      among the MHC class I genes.

PMID- 12183446
TI  - Phosphatidylinositol 3-kinase is a key regulator of early phase differentiation
      in keratinocytes.
AB  - The survival and growth of epithelial cells depend on adhesion to the
      extracellular matrix. Because epidermal keratinocytes differentiate as they leave
      the basement membrane, an adhesion signal may regulate the initiation of
      differentiation. Phosphatidylinositol 3-kinase (PI3K) is a fundamental signaling
      molecule that regulates the adhesion signal. Transfection of a dominant negative
      form of PI3K into keratinocytes using an adenovirus vector resulted in
      significant morphological changes comparable to differentiation and the induction
      of differentiation markers, keratin (K) 1 and K10. In turn, transfection with the
      constitutively active form of PI3K almost completely abolished the induction of
      K1 and K10 by differentiation in suspension cultures using
      polyhydroxyethylmethacrylate-coated dishes. PI3K activity was lost in suspension
      culture, except by cells bearing the constitutively active form of PI3K. These
      data demonstrate that blockade of PI3K results in differentiation and that
      activation of PI3K prevents differentiation. Furthermore, expression of the
      dominant negative form of PI3K significantly inhibited keratinocyte adhesion to
      the extracellular matrix and reduced the surface expression of alpha(6) and
      beta(1) integrins in suspension culture. Moreover, expression of the active form
      of PI3K restored the mRNA levels of adhesion molecules that were reduced in
      suspension culture, including alpha(3), alpha(6), and beta(1) integrins, BP180,
      and BP230. In conclusion, loss of PI3K activity results in keratinocytes leaving
      the basement membrane and the initiation of a "default" differentiation
      mechanism.

PMID- 12183447
TI  - The role of tetrahydrobiopterin in the regulation of neuronal nitric-oxide
      synthase-generated superoxide.
AB  - Tetrahydrobiopterin (H(4)B) is a critical element in the nitric-oxide synthase
      (NOS) metabolism of l-arginine to l-citrulline and NO(.). It has been
      hypothesized that in the absence of or under nonsaturating levels of L-arginine
      where O(2) reduction is the primary outcome of NOS activation, H(4)B promotes the
      generation of H(2)O(2) at the expense of O(2)(-.). The experiments were designed
      to test this hypothesis. To test this theory, two different enzyme preparations,
      H(4)B-bound NOS I and H(4)B-free NOS I, were used. Initial rates of NADPH
      turnover and O(2) utilization were found to be considerably greater in the H(4)B
      bound NOS I preparation than in the H(4)B-free NOS I preparation. In contrast,
      the initial generation of O(2)(-.) from the H(4)B-free NOS I preparation was
      found to be substantially greater than that measured using the H(4)B-bound NOS I
      preparation. Finally, by spin trapping nearly all of the NOS I produced O(2)(-.),
      we found that the initial rate of H(2)O(2) production by H(4)B-bound NOS I was
      considerably greater than that for H(4)B-free NOS I.

PMID- 12183448
TI  - A unique glutamic acid-lysine (EK) domain acts as a splicing inhibitor.
AB  - SRrp86 is a unique member of the SR protein superfamily of splicing factors
      containing one RNA recognition motif and two serine-arginine (SR)-rich domains
      separated by an unusual glutamic acid-lysine (EK) rich region. Previously, we
      showed that SRrp86 could regulate alternative splicing by both positively and
      negatively modulating the activity of other SR proteins as long as the entire
      region encompassing the RS-EK-RS domains was intact. To further investigate the
      function and domains of SRrp86, we generated a series of chimeric proteins by
      swapping the RNA recognition motif and RS domains between SRrp86 and two
      canonical members of the SR superfamily, ASF/SF2 and SRp75. Although domain swaps
      between SRrp86 and ASF/SF2 showed that the RRMs primarily determined splicing
      activity, swaps between SRrp86 and SRp75 demonstrated that the RS domains could
      also determine activity. Because SRp75 also has two RS domains but lacks the EK
      domain, we further investigated the role of the EK domain and found that it acts
      to repress splicing and splice-site selection, both in vitro and in vivo.
      Incubation of extracts with peptides encompassing the EK-rich region inactivated
      splicing and insertion of the EK region into SRp75 abolished its ability to
      activate splicing. Thus, the unique EK domain of SRrp86 plays a modulatory role
      controlling RS domain function.

PMID- 12183449
TI  - C/EBPalpha regulates hepatic transcription of hepcidin, an antimicrobial peptide
      and regulator of iron metabolism. Cross-talk between C/EBP pathway and iron
      metabolism.
AB  - Originally identified as a gene up-regulated by iron overload in mouse liver, the
      HEPC gene encodes hepcidin, the first mammalian liver-specific antimicrobial
      peptide and potential key regulator of iron metabolism. Here we demonstrate that
      during rat liver development, amounts of HEPC transcripts were very low in fetal
      liver, strongly and transiently increased shortly after birth, and reappeared in
      adult liver. To gain insight into mechanisms that regulate hepatic expression of
      hepcidin, 5'-flanking regions of human and mouse HEPC genes were isolated and
      analyzed by functional and DNA binding assays. Human and mouse HEPC promoter
      luciferase reporter vectors exhibited strong basal activity in hepatoma HuH-7 and
      mouse hepatocytes, respectively, but not in non-hepatic U-2OS cells. We found
      that CCAAT/enhancer-binding protein alpha (C/EBPalpha) and C/EBPbeta were
      respectively very potent and weak activators of both human and mouse promoters.
      In contrast, co-expression of hepatocyte nuclear factor 4alpha (HNF4alpha) failed
      to induce HEPC promoter activity. By electrophoretic mobility shift assay we
      demonstrated that one putative C/EBP element found in the human HEPC promoter (
      250/-230) predominantly bound C/EBPalpha from rat liver nuclear extracts. Hepatic
      deletion of the C/EBPalpha gene resulted in reduced expression of HEPC
      transcripts in mouse liver. In contrast, amounts of HEPC transcripts increased in
      liver-specific HNF4alpha-null mice. Decrease of hepcidin mRNA in mice lacking
      hepatic C/EBPalpha was accompanied by iron accumulation in periportal
      hepatocytes. Finally, iron overload led to a significant increase of C/EBPalpha
      protein and HEPC transcripts in mouse liver. Taken together, these data
      demonstrate that C/EBPalpha is likely to be a key regulator of HEPC gene
      transcription and provide a novel mechanism for cross-talk between the C/EBP
      pathway and iron metabolism.

PMID- 12183450
TI  - A novel peptide isolated from a phage display library inhibits tumor growth and
      metastasis by blocking the binding of vascular endothelial growth factor to its
      kinase domain receptor.
AB  - Vascular endothelial growth factor (VEGF), one of the most important angiogenic
      factors, plays an essential role in both physiological and pathological
      angiogenesis. The VEGF receptor KDR/Flk-1 (a kinase domain receptor) mediates
      various biological activities of VEGF related to proliferation, differentiation,
      and migration of endothelial cells. Here we present a novel peptide designated
      K237-(HTMYYHHYQHHL), which was isolated from a phage-displayed peptide library,
      binding to KDR with high affinity and specificity. By interfering with the VEGF
      KDR interaction, the peptide K237 inhibited proliferation of cultured primary
      human umbilical vein endothelial cells induced by recombinant human VEGF(165) in
      a dose-dependent and cell type-specific manner. The peptide also exerted an anti
      angiogenesis activity in vivo as revealed using the chick embryo chorioallantoic
      membrane angiogenesis assay. Moreover, the peptide K237 significantly inhibited
      the growth of solid tumors implanted beneath the breasts and their metastases to
      lungs in severe combined immunodeficient mice. Taken together, these findings
      suggest that the peptide K237 can functionally disrupt the interaction between
      VEGF and the KDR receptor and cause potent biological effects that include the
      inhibition of angiogenesis and tumor growth. As a consequence, this peptide (and
      its future derivatives) may have use as a potential cancer therapy.

PMID- 12183451
TI  - Alkyl-lysophospholipid accumulates in lipid rafts and induces apoptosis via raft
      dependent endocytosis and inhibition of phosphatidylcholine synthesis.
AB  - The synthetic alkyl-lysophospholipid (ALP), 1-O-octadecyl-2-O-methyl-rac-glycero
      3-phosphocholine, is an antitumor agent that acts on cell membranes and can
      induce apoptosis. We investigated how ALP is taken up by cells, how it affects de
      novo biosynthesis of phosphatidylcholine (PC), and how critical this is to
      initiate apoptosis. We compared an ALP-sensitive mouse lymphoma cell line, S49,
      with an ALP-resistant variant, S49(AR). ALP inhibited PC synthesis at the
      CTP:phosphocholine cytidylyltransferase (CT) step in S49 cells, but not in
      S49(AR) cells. Exogenous lysophosphatidylcholine, providing cells with an
      alternative way (acylation) to generate PC, rescued cells from ALP-induced
      apoptosis, indicating that continuous rapid PC turnover is essential for cell
      survival. Apoptosis induced by other stimuli that do not target PC synthesis
      remained unaffected by lysophosphatidylcholine. Using monensin, low temperature
      and albumin back-extraction, we demonstrated that ALP is internalized by
      endocytosis, a process defective in S49(AR) cells. This defect neither involved
      clathrin-coated pit- nor fluid-phase endocytosis, but depended on lipid rafts,
      because disruption of these microdomains with methyl-beta-cyclodextrin or filipin
      (sequestering cholesterol) or bacterial sphingomyelinase reduced uptake of ALP.
      Furthermore, ALP was found accumulated in isolated rafts and disruption of rafts
      also prevented the inhibition of PC synthesis and apoptosis induction in S49
      cells. In summary, ALP is internalized by raft-dependent endocytosis to inhibit
      PC synthesis, which triggers apoptosis.

PMID- 12183453
TI  - Protein kinase C isoforms are translocated to microtubules in neurons.
AB  - Activation of protein kinase C (PKC) increases microtubule (MT) growth lifetimes,
      resulting in extension of a nocodazole-sensitive population of MTs in Aplysia
      growth cones. We examined whether the two phorbol ester-activated PKCs in
      Aplysia, the Ca(2+)-activated PKC Apl I and the Ca(2+)-independent PKC Apl II,
      are associated with these MTs. Phorbol esters translocated PKC to the Triton X
      100-insoluble fraction, and a significant portion of this translocated pool was
      sensitive to low concentrations of nocodazole. Low doses of nocodazole had no
      effect on the amount of PKC in the Triton X-100-insoluble fraction in the absence
      of phorbol esters, whereas higher doses of nocodazole reduced basal levels of PKC
      Apl II. The F-actin cytoskeletal disrupter, latrunculin A, removed both PKCs from
      the Triton X-100-insoluble fraction in both control and phorbol ester-treated
      nervous systems. PKC Apl II also directly interacted with purified MTs. In
      detergent-extracted cells, both PKCs immunolocalized predominantly with MTs. PKCs
      were associated with newly formed MTs invading the actin-rich peripheral growth
      cone domain after PKC activation. Our results are consistent with a central role
      for PKCs in regulating MT extension.

PMID- 12183452
TI  - Paclitaxel-resistant human ovarian cancer cells undergo c-Jun NH2-terminal kinase
      mediated apoptosis in response to noscapine.
AB  - We have previously discovered the opium alkaloid noscapine as a microtubule
      interacting agent that binds to tubulin, alters the dynamics of microtubule
      assembly, and arrests mammalian cells at mitosis (Ye, K., Ke, Y., Keshava, N.,
      Shanks, J., Kapp, J. A., Tekmal, R. R., Petros, J., and Joshi, H. C. (1998) Proc.
      Natl. Acad. Sci. U. S. A. 95, 1601-1606; Ye, K., Zhou, J., Landen, J. W.,
      Bradbury, E. M., and Joshi, H. C. (2001) J. Biol. Chem. 276, 46697-46700; Zhou,
      J., Panda, D., Landen, J. W., Wilson, L., and Joshi, H. C. (2002) J. Biol. Chem.
      277, 17200-17208). Here we show that noscapine does not compete with paclitaxel
      for tubulin binding and can efficiently inhibit the proliferation of both
      paclitaxel-sensitive and paclitaxel-resistant human ovarian carcinoma cells (i.e.
      the parental cell line 1A9 and two derivative cell lines, 1A9PTX10 and 1A9PTX22,
      which harbor beta-tubulin mutations that impair paclitaxel-tubulin interaction
      (Giannakakou, P., Sackett, D. L., Kang, Y. K., Zhan, Z., Buters, J. T., Fojo, T.,
      and Poruchynsky, M. S. (1997) J. Biol. Chem. 272, 17118-17125). Strikingly, these
      cells undergo apoptotic death upon noscapine treatment, accompanied by activation
      of the c-Jun NH(2)-terminal kinases (JNK). Furthermore, inhibition of JNK
      activity by treatment with antisense oligonucleotide or transfection with
      dominant-negative JNK blocks noscapine-induced apoptosis. These findings thus
      indicate a great potential for noscapine in the treatment of paclitaxel-resistant
      human cancers. In addition, our results suggest that the JNK pathway plays an
      essential role in microtubule inhibitor-induced apoptosis.

PMID- 12183454
TI  - ClC-3 is a fundamental molecular component of volume-sensitive outwardly
      rectifying Cl- channels and volume regulation in HeLa cells and Xenopus laevis
      oocytes.
AB  - Volume-sensitive osmolyte and anion channels (VSOACs) are activated upon cell
      swelling in most vertebrate cells. Native VSOACs are believed to be a major
      pathway for regulatory volume decrease (RVD) through efflux of chloride and
      organic osmolytes. ClC-3 has been proposed to encode native VSOACs in Xenopus
      laevis oocytes and in some mammalian cells, including cardiac and vascular smooth
      muscle cells. The relationship between the ClC-3 chloride channel, the native
      volume-sensitive osmolyte and anion channel (VSOAC) currents, and cell volume
      regulation in HeLa cells and X. laevis oocytes was investigated using ClC-3
      antisense. In situ hybridization in HeLa cells, semiquantitative and real-time
      PCR, and immunoblot studies in HeLa cells and X. laevis oocytes demonstrated the
      presence of ClC-3 mRNA and protein, respectively. Exposing both cell types to
      hypotonic solutions induced cell swelling and activated native VSOACs. Transient
      transfection of HeLa cells with ClC-3 antisense oligonucleotide or X. laevis
      oocytes injected with antisense cRNA abolished the native ClC-3 mRNA transcript
      and protein and significantly reduced the density of native VSOACs activated by
      hypotonically induced cell swelling. In addition, antisense against native ClC-3
      significantly impaired the ability of HeLa cells and X. laevis oocytes to
      regulate their volume. These results suggest that ClC-3 is an important molecular
      component underlying VSOACs and the RVD process in HeLa cells and X. laevis
      oocytes.

PMID- 12183455
TI  - Characterization of phosphatidylinositol 3-kinase-dependent phosphorylation of
      the hydrophobic motif site Thr(389) in p70 S6 kinase 1.
AB  - Phosphorylation of the highly conserved hydrophobic motif site in AGC kinases is
      necessary for phosphotransferase activity. Phosphorylation of this motif
      (FLGFT389Y) in p70 S6 kinase (S6K1) is both rapamycin- and wortmannin-sensitive,
      suggesting a role for both mammalian target of rapamycin- and
      phosphatidylinositol 3-kinase-dependent pathways. We report here that co
      expression of phosphoinositide-dependent kinase-1 (PDK1) and the
      phosphatidylinositol 3-kinase-regulated atypical protein kinase Czeta cooperate
      to increase both phosphorylation of the hydrophobic motif site Thr(389), as well
      as the activation loop site Thr(229). Interestingly, although PDK1 alone can
      promote an increase in Thr(389) phosphorylation in both wild type S6K1 and a
      kinase-inactive mutant of S6K1, the cooperative effect between PDK1 and protein
      kinase Czeta required S6K1 activity. Furthermore, Akt, another
      phosphatidylinositol 3-kinase effector and regulator of S6K1, also increased
      Thr(389) phosphorylation in a S6K1 activity-dependent manner. Consistent with
      this, epidermal growth factor-induced Thr(389) phosphorylation in wild type S6K1
      persisted for up to 120 min, whereas kinase-inactive mutants of S6K1 displayed
      only a reduced and transient increase in Thr(389) phosphorylation. We conclude
      that S6K1 activity is required for maximal Thr(389) phosphorylation by mitogens
      and by multiple phosphatidylinositol 3-kinase-dependent inputs including PDK1,
      PKCzeta, and Akt, and we propose that autophosphorylation is an important
      regulatory mechanism for phosphorylation of the hydrophobic motif Thr(389) site
      in S6K1.

PMID- 12183456
TI  - Viroporin-mediated membrane permeabilization. Pore formation by nonstructural
      poliovirus 2B protein.
AB  - Enterovirus nonstructural 2B protein is involved in cell membrane
      permeabilization during late viral infection. Here we analyze the pore forming
      activity of poliovirus 2B and several of its variants. Solubilization of 2B
      protein was achieved by generating a fusion protein comprised of poliovirus 2B
      attached to a maltose-binding protein (MBP) as an N-terminal solubilization
      partner. MBP-2B was assayed using large unilamellar vesicles as target membranes.
      This fusion protein was able to assemble into discrete structures that disrupted
      the permeability barrier of vesicles composed of anionic phospholipids. The
      transbilayer aqueous connections generated by MBP-2B were stable over time,
      allowing the passage of solutes of molecular mass under 1,000 Da. Oligomerization
      was investigated using fluorescence resonance energy transfer. Our data indicate
      that MBP-2B aggregation occurs at the membrane surface. Moreover, MBP-2B binding
      to membranes promoted the formation of SDS-resistant tetramers. We conclude that
      MBP-2B forms oligomers capable of generating a tetrameric aqueous pore in lipid
      bilayers. These findings are the first evidence of viroporin activity shown by a
      protein from a naked animal virus.

PMID- 12183457
TI  - Differential activation of p53 by the various adducts of mitomycin C.
AB  - Mitomycin C (MC) is a cytotoxic chemotherapeutic agent that causes DNA damage in
      the form of DNA cross-links as well as a variety of DNA monoadducts and is known
      to induce p53. The various DNA adducts formed upon treatment of mouse mammary
      tumor cells with MC as well as 10-decarbamoyl MC (DMC) and 2,7-diaminomitosene
      (2,7-DAM), the major MC metabolite, have been elucidated. The cytotoxicity of DMC
      parallels closely that of MC in a number of rodent cell lines tested, whereas 2,7
      DAM is relatively noncytotoxic. In this study, we investigate the ability of MC,
      DMC, and 2,7-DAM to activate p53 at equidose concentrations by treating tissue
      culture cell lines with the three mitomycins. Whereas MC and DMC induced p53
      protein levels and increased the levels of p21 and Gadd45 mRNA, 2,7-DAM did not.
      Furthermore, MC and DMC, but not 2,7-DAM, were able to induce apoptosis
      efficiently in ML-1 cells. Therefore the 2,7-DAM monoadducts were unable to
      activate the p53 pathway. Interestingly, DMC was able to initiate apoptosis via a
      p53-independent pathway whereas MC was not. This is the first finding that
      adducts of a multiadduct type DNA-damaging agent are differentially recognized by
      DNA damage sensor pathways.

PMID- 12183458
TI  - Plexin B regulates Rho through the guanine nucleotide exchange factors leukemia
      associated Rho GEF (LARG) and PDZ-RhoGEF.
AB  - Plexins represent a novel family of transmembrane receptors that transduce
      attractive and repulsive signals mediated by the axon-guiding molecules
      semaphorins. Emerging evidence implicates Rho GTPases in these biological events.
      However, Plexins lack any known catalytic activity in their conserved cytoplasmic
      tails, and how they transduce signals from semaphorins to Rho is still unknown.
      Here we show that Plexin B2 associates directly with two members of a recently
      identified family of Dbl homology/pleckstrin homology containing guanine
      nucleotide exchange factors for Rho, PDZ-RhoGEF, and Leukemia-associated Rho GEF
      (LARG). This physical interaction is mediated by their PDZ domains and a PDZ
      binding motif found only in Plexins of the B family. In addition, we show that
      ligand-induced dimerization of Plexin B is sufficient to stimulate endogenous
      RhoA potently and to induce the reorganization of the cytoskeleton. Moreover,
      overexpression of the PDZ domain of PDZ-RhoGEF but not its regulator of G protein
      signaling domain prevents cell rounding and neurite retraction of differentiated
      PC12 cells induced by activation of endogenous Plexin B1 by semaphorin 4D. The
      association of Plexins with LARG and PDZ-RhoGEF thus provides a direct molecular
      mechanism by which semaphorins acting on Plexin B can control Rho, thereby
      regulating the actin-cytoskeleton during axonal guidance and cell migration.

PMID- 12183459
TI  - The transmembrane domains of the ABC multidrug transporter LmrA form a
      cytoplasmic exposed, aqueous chamber within the membrane.
AB  - The ABC multidrug transporter LmrA of Lactococcus lactis consists of six putative
      transmembrane segments (TMS) and a nucleotide binding domain. LmrA functions as a
      homodimer in which the two membrane domains form the solute translocation path
      across the membrane. To obtain structural information of LmrA a cysteine scanning
      accessibility approach was used. Cysteines were introduced in the cysteine-less
      wild-type LmrA in each hydrophilic loop and in TMS 6, and each membrane-embedded
      aromatic residue was mutated to cysteine. Of the 41 constructed single cysteine
      mutants, only one mutant, L301C, was not expressed. Most single-cysteine mutants
      were capable of drug transport and only three mutants, F37C, M299C, and N300C,
      were inactive, indicating that none of the aromatic residues in the transmembrane
      regions of LmrA are crucial for substrate binding or transport. Modification of
      the active mutants with N-ethylmaleimide blocked the transport activity in five
      mutants (S132C, L174C, S206C, S234C, and L292C). All cysteine residues in
      external and internal loops were accessible to fluorescein maleimide. The
      labeling experiments also showed that this thiol reagent cannot cross the
      membrane under the conditions used and confirmed the presence of six TMSs in each
      monomeric half of the transporter. Surprisingly, several single cysteines in the
      predicted TMSs could also be labeled by the bulky fluorescein maleimide molecule,
      suggesting unrestricted accessibility via an aqueous pathway. The periodicity of
      fluorescein maleimide accessibility of residues 291 to 308 in TMS 6 showed that
      this membrane-spanning alpha-helix has one face of the helix exposed to an
      aqueous cavity along its full-length. This finding, together with the solvent
      accessibility of 11 of 15 membrane-embedded aromatic residues, indicates that the
      transmembrane domains of the LmrA transporter form, under nonenergized
      conditions, an aqueous chamber within the membrane, which is open to the
      intracellular milieu.

PMID- 12183460
TI  - Structure-function analysis of HscC, the Escherichia coli member of a novel
      subfamily of specialized Hsp70 chaperones.
AB  - Hsp70 chaperones assist protein folding processes through nucleotide-controlled
      cycles of substrate binding and release. In our effort to understand the
      structure-function relationship within the Hsp70 family of proteins, we
      characterized the Escherichia coli member of a novel Hsp70 subfamily, HscC, and
      identified considerable differences to the well studied E. coli homologue, DnaK,
      which together suggest that HscC is a specialized chaperone. The basal ATPase
      cycle of HscC had k(cat) and K(m) values that were 8- and 10,000-fold higher than
      for DnaK. The HscC ATPase was not affected by the nucleotide exchange factor of
      DnaK GrpE and stimulated 8-fold by DjlC, a DnaJ protein with a putative
      transmembrane domain, but not by other DnaJ proteins tested. Substrate binding
      dynamics and substrate specificity differed significantly between HscC and DnaK.
      These differences are explicable by distinct structural variations. HscC does not
      have general chaperone activity because it did not assist refolding of a
      denatured model substrate. In vivo, HscC failed to complement temperature
      sensitivity of DeltadnaK cells. Deletion of hscC caused a slow growth phenotype
      that was suppressed after several generations. Triple knock-outs of all E. coli
      genes encoding Hsp70 proteins (DeltadnaK DeltahscA DeltahscC) were viable,
      indicating that Hsp70 proteins are not strictly essential for viability. An
      extensive search for DeltahscC phenotypes revealed a hypersensitivity to Cd(2+)
      ions and UV irradiation, suggesting roles of HscC in the cellular response to
      these stress treatments. Together our data show that the Hsp70 structure exhibits
      an astonishing degree of adaptive variations to accommodate requirements of a
      specialized function.

PMID- 12183461
TI  - The gate of the influenza virus M2 proton channel is formed by a single
      tryptophan residue.
AB  - The influenza virus M2 proton-selective ion channel is known to be essential for
      acidifying the interior of virions during virus uncoating in the lumen of
      endosomes. The M2 protein is a homotetramer that contains four 19-residue
      transmembrane (TM) domains. These TM domains are multifunctional, because they
      contain the channel pore and also anchor the protein in membranes. The M2 protein
      is gated by pH, and thus we have measured pH-gated currents, the accessibility of
      the pore to Cu2+, and the effect of a protein-modifying reagent for a series of
      TM domain mutant M2 proteins. The results indicate that gating of the M2 ion
      channel is governed by a single side chain at residue 41 of the TM domain and
      that this property is mediated by an indole moiety. Unlike many ion channels
      where the gate is formed by a whole segment of a protein, our data suggest a
      model of striking simplicity for the M2 ion channel protein, with the side chain
      of Trp(41) blocking the pore of the M2 channel when pH(out) is high and with this
      side chain leaving the pore when pH(out) is low. Thus, the Trp(41) side chain
      acts as the gate that opens and closes the pore.

PMID- 12183462
TI  - Tyrosine-sulfated peptides functionally reconstitute a CCR5 variant lacking a
      critical amino-terminal region.
AB  - Entry of most primary human immunodeficiency virus, type 1 (HIV-1) isolates into
      their target cells requires the cellular receptor CD4 and the G protein-coupled
      chemokine coreceptor CCR5. An acidic, tyrosine-rich, and tyrosine-sulfated domain
      of the CCR5 amino terminus plays a critical role in the ability of CCR5 to serve
      as an HIV-1 coreceptor, and tyrosine-sulfated peptides based on this region
      physically associate with the HIV-1 envelope glycoprotein gp120 and slow HIV-1
      entry into CCR5-expressing cells. Here we show that the same tyrosine-sulfated
      peptides, but not their unsulfated analogs, can restore the HIV-1 coreceptor
      activity of a CCR5 variant lacking residues 2-17 of its amino terminus.
      Additionally, these sulfated peptides restored the ability of this CCR5 variant
      to mobilize calcium in response to the chemokines macrophage inflammatory factors
      1alpha and 1beta. These observations show that a tyrosine-sulfated region of the
      CCR5 amino terminus can function independently to mediate association of
      chemokines and the HIV-1 envelope glycoprotein with the remaining domains of
      CCR5.

PMID- 12183463
TI  - Interactions of inositol 1,4,5-trisphosphate (IP(3)) receptors with synthetic
      poly(ethylene glycol)-linked dimers of IP(3) suggest close spacing of the IP(3)
      binding sites.
AB  - The distances between the inositol 1,4,5-trisphosphate (IP(3))-binding sites of
      tetrameric IP(3) receptors were probed using dimers of IP(3) linked by
      poly(ethylene glycol) (PEG) molecules of differing lengths (1-8 nm). Each of the
      dimers potently stimulated (45)Ca(2+) release from permeabilized cells expressing
      predominantly type 1 (SH-SY5Y cells) or type 2 (hepatocytes) IP(3) receptors. The
      shortest dimers, with PEG linkers of an effective length of 1.5 nm or less, were
      the most potent, being 3-4-fold more potent than IP(3). In radioligand binding
      experiments using cerebellar membranes, the shortest dimers bound with highest
      affinity, although the longest dimer (8 nm) also bound with almost 4-fold greater
      affinity than IP(3). The affinity of monomeric IP(3) with only the PEG attached
      was 2-fold weaker than IP(3), confirming that the increased affinity of the
      dimers requires the presence of both IP(3) motifs. The increased affinity of the
      long dimer probably results from the linked IP(3) molecules binding to sites on
      different receptors, because the dimer bound with greater affinity than IP(3) to
      cerebellar membranes, where receptors are densely packed, but with the same
      affinity as IP(3) to purified receptors. IP(3) and the IP(3) dimers, irrespective
      of their length, bound with similar affinity to a monomeric IP(3)-binding domain
      of the type 1 IP(3) receptor expressed in bacteria. Short dimers therefore bind
      with increased affinity only when the receptor is tetrameric. We conclude that
      the four IP(3)-binding sites of an IP(3) receptor may be separated by as little
      as 1.5 nm and are therefore likely to be placed centrally in this large (25 x 25
      nm) structure, consistent with previous work indicating a close association
      between the central pore and the IP(3)-binding sites of the IP(3) receptor.

PMID- 12183464
TI  - Oxidative modification of aldose reductase induced by copper ion. Definition of
      the metal-protein interaction mechanism.
AB  - Aldose reductase (ALR2) is susceptible to oxidative inactivation by copper ion.
      The mechanism underlying the reversible modification of ALR2 was studied by mass
      spectrometry, circular dichroism, and molecular modeling approaches on the enzyme
      purified from bovine lens and on wild type and mutant recombinant forms of the
      human placental and rat lens ALR2. Two equivalents of copper ion were required to
      inactivate ALR2: one remained weakly bound to the oxidized protein whereas the
      other was strongly retained by the inactive enzyme. Cys(303) appeared to be the
      essential residue for enzyme inactivation, because the human C303S mutant was the
      only enzyme form tested that was not inactivated by copper treatment. The final
      products of human and bovine ALR2 oxidation contained the intramolecular
      disulfide bond Cys(298)-Cys(303). However, a Cys(80)-Cys(303) disulfide could
      also be formed. Evidence for an intramolecular rearrangement of the Cys(80)
      Cys(303) disulfide to the more stable product Cys(298)-Cys(303) is provided.
      Molecular modeling of the holoenzyme supports the observed copper sequestration
      as well as the generation of the Cys(80)-Cys(303) disulfide. However, no evidence
      of conditions favoring the formation of the Cys(298)-Cys(303) disulfide was
      observed. Our proposal is that the generation of the Cys(298)-Cys(303) disulfide,
      either directly or by rearrangement of the Cys(80)-Cys(303) disulfide, may be
      induced by the release of the cofactor from ALR2 undergoing oxidation. The
      occurrence of a less interactive site for the cofactor would also provide the
      rationale for the lack of activity of the disulfide enzyme forms.

PMID- 12183465
TI  - An RNA helicase, DDX1, interacting with poly(A) RNA and heterogeneous nuclear
      ribonucleoprotein K.
AB  - Heterogeneous nuclear ribonucleoprotein K (hnRNP K) is a multifunctional protein
      known to be involved in the regulation of transcription, translation, nuclear
      transport, and signal transduction. To systematically obtain insight into
      mechanisms of hnRNP K activities, we set out to identify protein factors that
      interact with hnRNP K by using glutathione S-transferase-hnRNP K affinity
      chromatography followed by liquid chromatography/mass spectrometry/mass
      spectrometry analysis. Several partner proteins in the K562 cell lysates were
      identified through this method. One of them is a DEAD box-containing putative RNA
      helicase, DDX1. In vitro binding and co-immunoprecipitation studies confirmed the
      protein-protein interaction between hnRNP K with DDX1, and the region spanning
      amino acids 1-276 of hnRNP K is apparently responsible for its physical
      interaction with DDX1. Interestingly, their interaction was disrupted by the
      addition of poly(C), poly(A), and poly(U) RNA substrates. We found that DDX1 was
      a homopolymeric poly(A) RNA-binding protein. On the other hand, the ATPase
      activity of the purified recombinant DDX1 protein was stimulated by these
      homopolymeric RNAs and yeast total RNA but not by DNA. Moreover, the
      immunoprecipitated DDX1 complex but not purified DDX1 can unwind double-stranded
      RNA having single-stranded poly(A) overhangs.

PMID- 12183467
TI  - Ganglioside modulation regulates epithelial cell adhesion and spreading via
      ganglioside-specific effects on signaling.
AB  - Gangliosides are implicated in regulating cell adhesion and migration on
      fibronectin by binding with the alpha(5) subunit of alpha(5)beta(1) integrin.
      However, the effects of gangliosides on cell spreading and related signaling
      pathways are unknown. Increases in gangliosides GT1b and GD3 inhibited spreading
      on fibronectin, concurrent with inhibition of Src and focal adhesion kinase.
      Although antibody blockade of GT1b or GD3 function and gene-modulated ganglioside
      depletion stimulated spreading and activated Src and focal adhesion kinase, the
      augmented spreading by disruption of GT1b function, but not by disruption of GD3
      function, was inhibited by blockade of Src and focal adhesion kinase activation.
      In contrast, inhibitors of protein kinase C prevented the stimulation of
      spreading by GD3 functional inhibition, but not by GT1b functional blockade.
      Modulation of either GT1b or GD3 content affected phosphoinositol 3-kinase
      activation, and inhibition of this activation reversed the stimulation of cell
      spreading by anti-GD3 antibody, anti-GT1b antibody, and ganglioside depletion,
      suggesting that phosphoinositol 3-kinase is an intermediate in both the FAK/Src
      and protein kinase C pathways that lead to cell spreading. These studies
      demonstrate that epithelial cell ganglioside GT1b modulates cell spreading
      through alpha(5)beta(1)/FAK and phosphoinositol 3-kinase signaling, whereas GD3
      modulated spreading appears to involve phosphoinositol 3-kinase-dependent protein
      kinase C signaling.

PMID- 12183466
TI  - Molecular cloning of a novel chaperone-like protein induced by rhabdovirus
      infection with sequence similarity to the bacterial extracellular solute-binding
      protein family 5.
AB  - Previously we demonstrated that a novel stress protein is induced in fish cells
      by the infection of a fish rhabdovirus (Cho W. J., Cha, S. J., Do, J. W., Choi,
      J. Y., Lee, J. Y., Jeong, C. S., Cho, K. J., Choi, W. S., Kang, H. S., Kim, H.
      D., and Park, J. W. (1997) Biochem. Biophys. Res. Commun. 233, 316-319). In this
      paper, we present the molecular cloning and characterization of a gene encoding
      this protein named virus-inducible stress protein (VISP). The VISP was purified
      partially by immunoprecipitation using a monoclonal antibody against the VISP and
      further purified by the electroelution from a SDS-PAGE gel. The protein was
      subjected to internal protein sequencing, and the sequence of three peptides was
      determined. Degenerate oligonucleotides based on the three peptide sequences were
      used to screen a cDNA library from rhabdovirus-infected CHSE-214 fish cells, and
      a cDNA of a 2193-bp open reading frame encoding the VISP with 730 amino acid
      residues (M(r) = 79.84) was identified. Whereas the nucleotide sequence of VISP
      shows no similarity with other genes in the GenBank(TM), the amino acid sequence
      of the VISP has similarity with the bacterial extracellular solute-binding
      protein family 5 (SBP_bac_5) that is proposed to have chaperone activity. Thus,
      we explored whether the VISP also had chaperone-like activity. Purified
      recombinant VISP expressed in Escherichia coli promoted the functional folding of
      alpha-glucosidase after urea denaturation and also prevented thermal aggregation
      of alcohol dehydrogenase. These results suggest that the VISP has amino acid
      sequence similarity with SBP_bac_5 and that it has chaperone activity that may
      play a role in virus infection.

PMID- 12183468
TI  - Costimulation of Gi- and G12/G13-mediated signaling pathways induces integrin
      alpha IIbbeta 3 activation in platelets.
AB  - Platelet activation is a complex process induced by a variety of stimuli, which
      act in concert to ensure the rapid formation of a platelet plug at places of
      vascular injury. We show here that fibrillar collagen, which initiates platelet
      activation at the damaged vessel wall, activates only a small fraction of
      platelets in suspension directly, whereas the majority of platelets becomes
      activated by mediators released from collagen-activated platelets. In Galpha(q)
      deficient platelets that do not respond with activation of integrin
      alpha(IIb)beta(3) to a variety of mediators like thromboxane A2 (TXA2), thrombin,
      or ADP, collagen at high concentrations was able to induce aggregation, an effect
      that could be blocked by antagonists of the TXA2 or P2Y12 receptors. The
      activation of TXA2 or P2Y12 receptors alone, which in Galpha(q)-deficient
      platelets couple to G12/G13 and Gi, respectively, did not induce platelet
      integrin activation or aggregation. However, concomitant activation of both
      receptors resulted in irreversible integrin alpha(IIb)beta3-mediated aggregation
      of Galpha(q)-deficient platelets. Thus, the activation of G12/G13- and Gi
      mediated signaling pathways is sufficient to induce integrin alpha(IIb)beta3
      activation. Although G(q)-mediated signaling plays an important role in platelet
      activation, it is not strictly required for the activation of integrin
      alpha(IIb)beta3. This indicates that the efficient induction of platelet
      aggregation through G-protein-coupled receptors is an integrated response
      mediated by various converging G-protein-mediated signaling pathways involving
      G(q) and G(i) as well as G12/G13.

PMID- 12183469
TI  - Two highly related p66 proteins comprise a new family of potent transcriptional
      repressors interacting with MBD2 and MBD3.
AB  - Methyl-CpG-binding domain proteins (MBD) mediate functional responses of
      methylated DNA. MBD2 and MBD3 are components of the MeCP1 protein complex, which
      contains the Mi-2/NuRD complex and includes 66- and 68-kDa polypeptides. Here we
      identified two highly related 66-kDa proteins in a yeast two-hybrid screen with
      MBD2b. Based on the high degree of sequence conservation to the previously
      identified Xenopus p66 subunit of the Mi-2/NuRD complex, we termed these proteins
      hp66alpha and hp66beta. hp66alpha is the human orthologue of Xenopus p66, whereas
      hp66beta, previously identified as a component of the human MeCP1 complex, is a
      second member of a p66 gene family. Coprecipitation of hp66alpha and MBD2
      demonstrates their in vivo association. Furthermore, confocal microscopy shows a
      nuclear colocalization of hp66alpha with hp66beta and MBD2 in a speckled pattern.
      hp66alpha is a potent transcriptional repressor reducing gene activity about 100
      fold and is ubiquitously coexpressed with hp66beta in cell lines and in fetal and
      adult tissues. We demonstrate direct binding of both p66 family members to MBD2
      as well as MBD3. Interestingly, hp66alpha, which binds with a higher affinity
      than hp66beta, interacts via two interaction domains in contrast to a single
      interaction domain present in hp66beta. These results demonstrate that two highly
      related mammalian p66 proteins display overlapping functions and are involved in
      methylation dependent transcriptional repression.

PMID- 12183470
TI  - Cofactor binding to Escherichia coli D-3-phosphoglycerate dehydrogenase induces
      multiple conformations which alter effector binding.
AB  - The inhibition of Escherichia coli d-3-phosphoglycerate dehydrogenase by l-serine
      is positively cooperative with a Hill coefficient of approximately 2, whereas the
      binding of the inhibitor, l-serine, to the apoenzyme displays positive
      cooperativity in the binding of the first two serine molecules and negative
      cooperativity in the binding of the last two serine molecules. An earlier report
      demonstrated that the presence of phosphate appeared to lessen the degree of both
      the positive and negative cooperativity, but the cause of this effect was
      unknown. This study demonstrates that the presence of intrinsically bound NADH
      was responsible to a substantial degree for this effect. In addition, this study
      also provides evidence for negative cooperativity in NADH binding and for at
      least two NADH-induced conformational forms of the enzyme that bind the inhibitor
      in the physiological range. Successive binding of NADH to the enzyme resulted in
      an increase in the affinity for the first inhibitor ligand bound and a lessening
      of both the positive and negative cooperativity of inhibitor binding as compared
      with that seen in the absence of NADH. This effect was specific for NADH and was
      not observed in the presence of NAD+ or the substrate alpha-ketoglutarate.
      Conversely, the binding of l-serine did not have a significant effect on the
      stoichiometry of NADH binding, consistent with it being a V-type allosteric
      system. Thus, cofactor-related conditions were found in equilibrium binding
      experiments that significantly altered the cooperativity of inhibitor binding.
      Since the result of inhibitor binding is a reduction in the catalytic activity,
      the binding of inhibitor to these NADH-induced conformers must also induce
      additional conformations that lead to differential inhibition of catalytic
      activity.

PMID- 12183471
TI  - ATP-dependent unwinding of a minimal origin of DNA replication by the origin
      binding protein and the single-strand DNA-binding protein ICP8 from herpes
      simplex virus type I.
AB  - The Herpes simplex virus type I origin-binding protein, OBP, is encoded by the
      UL9 gene. OBP binds the origin of DNA replication, oriS, in a cooperative and
      sequence-specific manner. OBP is also an ATP-dependent DNA helicase. We have
      recently shown that single-stranded oriS folds into a unique and evolutionarily
      conserved conformation, oriS*, which is stably bound by OBP. OriS* contains a
      stable hairpin formed by complementary base pairing between box I and box III in
      oriS. Here we show that OBP, in the presence of the single-stranded DNA-binding
      protein ICP8, can convert an 80-base pair double-stranded minimal oriS fragment
      to oriS* and form an OBP-oriS* complex. The formation of an OBP-oriS* complex
      requires hydrolysable ATP. We also demonstrate that OBP in the presence of ICP8
      and ATP promotes slow but specific and complete unwinding of duplex minimal oriS.
      The possibility that the OBP-oriS* complex may serve as an assembly site for the
      herpes virus replisome is discussed.

PMID- 12183472
TI  - Exercise-induced immunodepression- plasma glutamine is not the link.
AB  - The amino acid glutamine is known to be important for the function of some immune
      cells in vitro. It has been proposed that the decrease in plasma glutamine
      concentration in relation to catabolic conditions, including prolonged,
      exhaustive exercise, results in a lack of glutamine for these cells and may be
      responsible for the transient immunodepression commonly observed after acute,
      exhaustive exercise. It has been unclear, however, whether the magnitude of the
      observed decrease in plasma glutamine concentration would be great enough to
      compromise the function of immune cells. In fact, intracellular glutamine
      concentration may not be compromised when plasma levels are decreased
      postexercise. In addition, a number of recent intervention studies with glutamine
      feeding demonstrate that, although the plasma concentration of glutamine is kept
      constant during and after acute, strenuous exercise, glutamine supplementation
      does not abolish the postexercise decrease in in vitro cellular immunity,
      including low lymphocyte number, impaired lymphocyte proliferation, impaired
      natural killer and lymphokine-activated killer cell activity, as well as low
      production rate and concentration of salivary IgA. It is concluded that, although
      the glutamine hypothesis may explain immunodepression related to other stressful
      conditions such as trauma and burn, plasma glutamine concentration is not likely
      to play a mechanistic role in exercise-induced immunodepression.

PMID- 12183473
TI  - Determinants of metabolic cost during submaximal cycling.
AB  - The metabolic cost of producing submaximal cycling power has been reported to
      vary with pedaling rate. Pedaling rate, however, governs two physiological
      phenomena known to influence metabolic cost and efficiency: muscle shortening
      velocity and the frequency of muscle activation and relaxation. The purpose of
      this investigation was to determine the relative influence of those two phenomena
      on metabolic cost during submaximal cycling. Nine trained male cyclists performed
      submaximal cycling at power outputs intended to elicit 30, 60, and 90% of their
      individual lactate threshold at four pedaling rates (40, 60, 80, 100 rpm) with
      three different crank lengths (145, 170, and 195 mm). The combination of four
      pedaling rates and three crank lengths produced 12 pedal speeds ranging from 0.61
      to 2.04 m/s. Metabolic cost was determined by indirect calorimetery, and power
      output and pedaling rate were recorded. A stepwise multiple linear regression
      procedure selected mechanical power output, pedal speed, and pedal speed squared
      as the main determinants of metabolic cost (R(2) = 0.99 +/- 0.01). Neither
      pedaling rate nor crank length significantly contributed to the regression model.
      The cost of unloaded cycling and delta efficiency were 150 metabolic watts and
      24.7%, respectively, when data from all crank lengths and pedal speeds were
      included in a regression. Those values increased with increasing pedal speed and
      ranged from a low of 73 +/- 7 metabolic watts and 22.1 +/- 0.3% (145-mm cranks,
      40 rpm) to a high of 297 +/- 23 metabolic watts and 26.6 +/- 0.7% (195-mm cranks,
      100 rpm). These results suggest that mechanical power output and pedal speed, a
      marker for muscle shortening velocity, are the main determinants of metabolic
      cost during submaximal cycling, whereas pedaling rate (i.e., activation
      relaxation rate) does not significantly contribute to metabolic cost.

PMID- 12183474
TI  - Strenuous but not moderate exercise increases the thrombotic tendency in healthy
      sedentary male volunteers.
AB  - We have investigated the effect of moderate and strenuous exercise on
      experimental arterial thrombus formation in men. Thrombogenesis was measured in
      15 sedentary healthy male volunteers at rest or immediately after two
      standardized exercise tests performed for 30 min on a bicycle ergometer. The
      exercises were performed at a constant load corresponding to either 50 or 70%
      maximal oxygen uptake. Thrombus formation was induced ex vivo by exposing a
      collagen-coated coverslip in a parallel plate perfusion chamber to native
      nonanticoagulated blood for 3 min. The shear rate at the collagen surface was
      2,600 s(-1). Platelet and fibrin deposition was quantified by immunoenzymatic
      methods. The results show that moderate exercise did not affect arterial thrombus
      formation. In contrast, platelet thrombus formation on collagen was increased on
      the average by 20% after 30 min at 70% maximal oxygen uptake (P = 0.03). Fibrin
      deposition on collagen remained unchanged with exercise, regardless of its
      intensity. Thus, with the use of a clinically relevant human experimental model
      of thrombosis, the present study suggests that exercise of heavy intensity may
      increase the risk for arterial thrombogenesis in sedentary young healthy male
      volunteers.

PMID- 12183475
TI  - alpha,beta-Methylene ATP elicits a reflex pressor response arising from muscle in
      decerebrate cats.
AB  - In part, the exercise pressor reflex is believed to be evoked by chemical stimuli
      signaling that blood supply to exercising muscles is not adequate to meet its
      metabolic demands. There is evidence that either ATP or adenosine may function as
      one of these chemical stimuli. For example, muscle interstitial concentrations of
      both substances have been found to increase during exercise. This finding led us
      to test the hypothesis that popliteal arterial injection of alpha,beta-methylene
      ATP (5, 20, and 50 microg/kg), which stimulates P2X receptors, and 2
      chloroadenosine (25 microg/kg), which stimulates P1 receptors, evokes reflex
      pressor responses in decerebrate, unanesthetized cats. We found that popliteal
      arterial injection of the two highest doses of alpha,beta-methylene ATP evoked
      pressor responses, whereas popliteal arterial injection of 2-chloroadenosine did
      not. In addition, the pressor responses evoked by alpha,beta-methylene ATP were
      blocked either by section of the sciatic nerve or by prior popliteal arterial
      injection of pyridoxal phosphate-6-azophenyl-2',4'-disulfonic acid (10 mg/kg), a
      selective P2-receptor antagonist. We conclude that the stimulation of P2
      receptors, which are accessible through the vascular supply of skeletal muscle,
      evokes reflex pressor responses. In addition, our findings are consistent with
      the hypothesis that the stimulation of P2 receptors comprises part of the
      metabolic error signal evoking the exercise pressor reflex.

PMID- 12183476
TI  - Pulmonary responses to tracheal or esophageal acidification in guinea pigs with
      airway inflammation.
AB  - The association between asthma and gastroesophageal reflux has been attributed to
      microaspiration of gastric contents and/or vagally mediated reflex
      bronchoconstriction. In previous experimental studies concerning the pulmonary
      effects of tracheal or esophageal acid infusion, only animals without airway
      inflammation have been studied. We assessed the effects of esophageal and
      tracheal administration of hydrochloric acid (HCl) on normal guinea pigs (GP) and
      GP with airway inflammation induced by repeated ovalbumin exposures. These GP
      were anesthetized (pentobarbital sodium) and received 1) 20 microl of either 0.2
      N HCl or saline into the trachea, or 2) 1 ml of either 1 N HCl or saline into the
      esophagus. Intratracheal HCl resulted in a significant increase in both
      respiratory system elastance and resistance (P < 0.001). There were no
      significant changes in respiratory mechanics when HCl was infused into the
      esophagus. In conclusion, we observed that infusion of large volumes of HCl into
      the esophagus did not change pulmonary mechanics significantly, even in guinea
      pigs with chronic allergen-induced airway inflammation. In contrast,
      intratracheal administration of small amounts of acid had substantial effects in
      normal GP and GP with airway inflammation.

PMID- 12183477
TI  - Differential adenosine sensitivity of diaphragm and skeletal muscle arterioles.
AB  - The hyperemic response in exercising skeletal muscle is dependent on muscle fiber
      type composition and fiber recruitment patterns, but the vascular control
      mechanisms producing exercise hyperemia in skeletal muscle remain poorly
      understood. The purpose of this study was to test the hypothesis that arterioles
      from white, low-oxidative skeletal muscle are less responsive to adenosine
      induced dilation than are arterioles from diaphragm (Dia) and red, high-oxidative
      skeletal muscle. Second-order arterioles (2As) were isolated from the white
      portion of gastrocnemius muscle (WG; low-oxidative, fast-twitch muscle tissue)
      and two types of high-oxidative skeletal muscle [Dia and red portion of
      gastrocnemius muscle (RG)] of rats. Results reveal that 2As from all three types
      of muscle dilated in response to the endothelium-dependent dilator acetylcholine
      (WG: 48 +/- 3%, Dia: 51 +/- 3%, RG: 74 +/- 3%). In contrast, adenosine dilated
      only 2As from WG (48 +/- 4%) and Dia (46 +/- 5%) but not those from RG (5 +/-
      5%). Thus adenosine-induced dilator responses differed among 2As of these
      different types of muscle tissue. However, the results do not support our
      hypothesis because 2As from Dia and WG dilated in response to adenosine, whereas
      2As from RG did not. We conclude that the adenosine responsiveness of 2As from
      rat skeletal muscle cannot be predicted only by the fiber-type composition or
      oxidative capacity of the skeletal muscle tissue wherein the arteriole lies.

PMID- 12183478
TI  - Effect of hypoxia on arterial baroreflex control of heart rate and muscle
      sympathetic nerve activity in humans.
AB  - We tested the hypothesis that acute hypoxia would alter the sensitivity of
      arterial baroreflex control of both heart rate and sympathetic vasoconstrictor
      outflow. In 16 healthy, nonsmoking, normotensive subjects (8 women, 8 men, age 20
      33 yr), we assessed baroreflex control of heart rate and muscle sympathetic nerve
      activity by using the modified Oxford technique during both normoxia and hypoxia
      (12% O(2)). Compared with normoxia, hypoxia reduced arterial O(2) saturation
      levels from 96.8 +/- 0.3 to 80.7 +/- 1.4% (P < 0.001), increased heart rate from
      59.8 +/- 2.4 to 79.4 +/- 2.9 beats/min (P < 0.001), increased mean arterial
      pressure from 96.7 +/- 2.5 to 105.0 +/- 3.3 mmHg (P = 0.002), and increased
      sympathetic activity 126 +/- 58% (P < 0.05). The sensitivity for baroreflex
      control of both heart rate and sympathetic activity was not altered by hypoxia
      (heart rate: -1.02 +/- 0.09 vs. -1.02 +/- 0.11 beats. min(-1). mmHg(-1); nerve
      activity: -5.6 +/- 0.9 vs. -6.2 +/- 0.9 integrated activity. beat(-1). mmHg(-1);
      both P > 0.05). Acute exposure to hypoxia reset baroreflex control of both heart
      rate and sympathetic activity to higher pressures without changes in baroreflex
      sensitivity.

PMID- 12183479
TI  - Lactate metabolism in resting and contracting canine skeletal muscle with
      elevated lactate concentration.
AB  - This study was undertaken to quantitatively account for the metabolic disposal of
      lactate in skeletal muscle exposed to an elevated lactate concentration during
      rest and mild-intensity contractions. The gastrocnemius plantaris muscle group
      (GP) was isolated in situ in seven anesthetized dogs. In two experiments, the
      muscles were perfused with an artificial perfusate with a blood lactate
      concentration of ~9 mM while normal blood gas/pH status was maintained with [U
      (14)C]lactate included to follow lactate metabolism. Lactate uptake and metabolic
      disposal were measured during two consecutive 40-min periods, during which the
      muscles rested or contracted at 1.25 Hz. Oxygen consumption averaged 10.1 +/- 2.0
      micromol. 100 g(-1). min(-1) (2.26 +/- 0.45 ml. kg(-1). min(-1)) at rest and
      143.3 +/- 16.2 micromol. 100 g(-1). min(-1) (32.1 +/- 3.63 ml. kg(-1). min(-1))
      during contractions. Lactate uptake was positive during both conditions,
      increasing from 10.5 micromol. 100 g(-1). min(-1) at rest to 25.0 micromol. 100
      g(-1). min(-1) during contractions. Oxidation and glycogen synthesis represented
      minor pathways for lactate disposal during rest at only 6 and 15%, respectively,
      of the [(14)C]lactate removed by the muscle. The majority of the [(14)C]lactate
      removed by the muscle at rest was recovered in the muscle extracts, suggesting
      that quiescent muscle serves as a site of passive storage for lactate carbon
      during high-lactate conditions. During contractions, oxidation was the dominant
      means for lactate disposal at >80% of the [(14)C]lactate removed by the muscle.
      These results suggest that oxidation is a limited means for lactate disposal in
      resting canine GP exposed to elevated lactate concentrations due to the muscle's
      low resting metabolic rate.

PMID- 12183480
TI  - Effects of ion transport inhibitors on MCh-mediated secretion from porcine airway
      submucosal glands.
AB  - Submucosal glands secrete macromolecules and liquid that are essential for normal
      airway function. To determine the mechanisms responsible for airway gland
      secretion and the interaction between gland secretion and epithelial ion
      transport, studies were performed in porcine tracheal epithelia by using the
      hillocks and Ussing techniques. No significant baseline gland fluid flux (J(G))
      was measured by the hillocks technique after 3 min, and the epithelia had an
      average potential difference of 7.5 +/- 0.5 mV (lumen negative) with a short
      circuit current of 73 +/- 4 microA/cm(2), as measured by the Ussing technique.
      The secretagogue methacholine induced concentration-dependent increases in J(G)
      after 3 min from 0.003 microl. min(-1). cm(-2) at 0.1 microM to 0.41 +/- 0.04
      microl. min(-1). cm(-2) at 1,000 microM, with a 0.9 +/- 0.1 mV hyperpolarization
      of the epithelium at 1,000 microM. When the epithelium was pretreated for 3 min
      with the sodium channel blocker amiloride, the methacholine (1,000 microM)
      induced J(G) increased to 0.67 +/- 0.09 microl. min(-1). cm(-2), and the
      hyperpolarization increased to 2.2 +/- 0.5 mV over the amiloride-pretreated
      level. When pretreated for 3 min with the chloride channel blocker diphenylamine
      2-carboxylic acid, the methacholine (1,000 microM)-induced J(G) was inhibited to
      0.20 +/- 0.06 microl. min(-1). cm(-2), and the methacholine-induced
      hyperpolarization was abolished. These data indicate that, in porcine airways,
      methacholine-induced J(G) may be increased by inhibition of sodium absorption and
      decreased by inhibition of chloride secretion.

PMID- 12183481
TI  - Diving response and arterial oxygen saturation during apnea and exercise in
      breath-hold divers.
AB  - This study addressed the effects of apnea in air and apnea with face immersion in
      cold water (10 degrees C) on the diving response and arterial oxygen saturation
      during dynamic exercise. Eight trained breath-hold divers performed steady-state
      exercise on a cycle ergometer at 100 W. During exercise, each subject performed
      30-s apneas in air and 30-s apneas with face immersion. The heart rate and
      arterial oxygen saturation decreased and blood pressure increased during the
      apneas. Compared with apneas in air, apneas with face immersion augmented the
      heart rate reduction from 21 to 33% (P < 0.001) and the blood pressure increase
      from 34 to 42% (P < 0.05). The reduction in arterial oxygen saturation from
      eupneic control was 6.8% during apneas in air and 5.2% during apneas with face
      immersion (P < 0.05). The results indicate that augmentation of the diving
      response slows down the depletion of the lung oxygen store, possibly associated
      with a larger reduction in peripheral venous oxygen stores and increased
      anaerobiosis. This mechanism delays the fall in alveolar and arterial PO(2) and,
      thereby, the development of hypoxia in vital organs. Accordingly, we conclude
      that the human diving response has an oxygen-conserving effect during exercise.

PMID- 12183483
TI  - Respiratory-related evoked potentials elicited by inspiratory occlusions in
      double-lung transplant recipients.
AB  - This study investigated the role of lung vagal afferents in the respiratory
      related evoked potential (RREP) response to inspiratory occlusions by using
      double-lung transplant recipients as a lung denervation model. Evoked potential
      recordings in response to inspiratory occlusions were obtained from 10 double
      lung transplant (DLT) recipients with normal lung function and 12 healthy control
      (Nor) subjects under the attend, ignore, and unoccluded conditions. Results
      demonstrated that early-latency RREP components (P(1), P(1a), N(f), and N(1))
      were not significantly different between the DLT and the Nor groups. The late
      latency RREP component (P(3)) was identifiable in all DLT subjects during the
      attend trial. However, P(3) latency was significantly longer in the DLT group
      compared with the Nor group. The zero-to-peak amplitude of P(3) was also
      significantly smaller in the DLT group than that in the Nor group during the
      attend trial. These results suggest that lung vagal afferents were not essential
      to elicit RREP responses, but may contribute to the cognitive processing of
      respiratory stimuli.

PMID- 12183482
TI  - Long-term effects of diet on leptin, energy intake, and activity in a model of
      diet-induced obesity.
AB  - This study investigated the effect of long-term high-fat sucrose (HFS) or low-fat
      complex-carbohydrate (LFCC) diet consumption on leptin, insulin, fat cell size,
      energy intake, and markers of activity to ascertain the role that leptin plays in
      long-term energy balance in a model of diet-induced obesity. Female Fischer 344
      rats were fed either a HFS or LFCC diet ad libitum for a period of 20 mo.
      Measurements of leptin concentration, insulin concentration, and adipocyte size
      were performed at 2 wk, 2 mo, 6 mo, and 20 mo. Body weight and energy intake were
      measured weekly for calculation of feed efficiency. Body temperature and activity
      levels were assessed over a 5-day period after 12 mo of the dietary intervention.
      Plasma leptin and insulin concentrations were significantly elevated within 2 wk
      of HFS diet consumption and remained elevated throughout the course of the study.
      After 2 mo, the adipocytes of the HFS group were significantly larger and
      continued to increase in size throughout the course of the study. A significant
      correlation was noted between leptin and adipocyte cell size (r = 0.96, P <
      0.01). However, despite elevated leptin, energy intake was similar, and the HFS
      group weighed significantly more than the LFCC group, as a result of a higher
      feed efficiency. There were no significant differences in body temperature or
      activity levels between the groups. These results demonstrate that a HFS diet
      causes hyperleptinemia and hyperinsulinemia before adipocyte size is increased
      and suggests that leptin resistance may be present or, alternatively, that leptin
      does not to play a major role in the long-term regulation of energy intake or
      activity levels in this model.

PMID- 12183484
TI  - Termination of inspiration by phase-dependent respiratory vagal feedback in awake
      normal humans.
AB  - Imperceptible levels of proportional assist ventilation applied throughout
      inspiration reduced inspiratory time (TI) in awake humans. More recently, the
      reduction in TI was associated with flow assist, but flow assist also reaches a
      maximum value early during inspiration. To test the separate effects of flow
      assist and timing of assist, we applied a pseudorandom binary sequence of flow
      assisted breaths during early, late, or throughout inspiration in eight normal
      subjects. We hypothesized that imperceptible flow assist would shorten TI most
      effectively when applied during early inspiration. Tidal volume, integrated
      respiratory muscle pressure per breath, TI, and TE were recorded. All stimuli
      (early, late, or flow assist applied throughout inspiration) resulted in a
      significant increase in inspiratory flow; however, only when the flow assist was
      applied during early inspiration was there a significant reduction in TI and the
      integrated respiratory muscle pressure per breath. These results provide further
      evidence that vagal feedback modulates breathing on a breath-by-breath basis in
      conscious humans within a physiological range of breath sizes.

PMID- 12183485
TI  - Effects of fixatives on function of pulmonary surfactant.
AB  - The structure of pulmonary surfactant films remains ill defined. Although
      plausible film fragments have been imaged by electron microscopy, questions about
      the significance of the findings and even about the true fixability of surfactant
      films by the usual fixatives glutaraldehyde (GA), osmium tetroxide (OsO(4)), and
      uranyl acetate (UA) have not been settled. We exposed functioning natural
      surfactant films to fixatives within a captive bubble surfactometer and analyzed
      the effect of fixatives on surfactant function. The capacity of surfactant to
      reach near-zero minimum surface tension on film compression was barely impaired
      after exposure to GA or OsO(4). Although neither GA nor OsO(4) prevented the
      surfactant from forming a surface active film, GA increased the equilibrium
      surface tension to above 30 mN/m, and both GA and OsO(4) decreased film stability
      as seen in the slowly rising minimum surface tension from 1 to ~5 mN/m in 10 min.
      In contrast, the effect of UA seriously impaired surface activity in that both
      adsorption and minimum surface tension were substantially increased. In
      conclusion, the fixatives tested in this study are not suitable to fix, i.e., to
      solidify, surfactant films. Evidently, however, OsO(4) and UA may serve as
      staining agents.

PMID- 12183487
TI  - Efficient design of the diaphragm: distribution of blood flow relative to
      mechanical advantage.
AB  - The mammalian diaphragm is composed of two separate muscles (costal and crural)
      connected by a central tendon that serves as a piston head for drawing air into
      the lungs. The two muscles are described as having different embryological
      origins, segmental innervations, and mechanical functions [De Troyer A, Sampson
      M, Sigrist S, and Macklem PT. Science 213: 237-238, 1981; De Troyer A, Sampson M,
      Sigrist S, and Macklem PT. J Appl Physiol 53: 30-39, 1982]. On the basis of
      regional blood flow measurements, the two muscles appear to be nonuniformly
      recruited at rest, but we anticipated that the two muscles would become uniformly
      recruited at heavy exercise to efficiently support the high energy requirements
      of ventilation. We used fluorescent microspheres to measure regional blood flow
      within the two muscles as an index of muscle recruitment from rest to heavy
      treadmill exercise in well-trained foxhounds. However, the heterogeneity of blood
      flow at rest persisted as exercise workloads were increased. Blood flow per gram
      of muscle remained twofold greater in ventral than dorsal regions of both muscles
      from rest to heavy exercise. This pattern was matched by a twofold greater
      regional mechanical advantage in ventral than dorsal regions of the two muscles
      measured anatomically. Hence blood flow was preferentially and efficiently
      distributed to those regions capable of generating the greatest inspiratory power
      independent of muscle mass. The two muscles were recruited from rest to heavy
      exercise as a single functional unit, not as two muscles under separate control.

PMID- 12183486
TI  - Postevent ventilation as a function of CO(2) load during respiratory events in
      obstructive sleep apnea.
AB  - Maintenance of eucapnia during sleep in obstructive sleep apnea (OSA) requires a
      balance between CO(2) loading during apnea and CO(2) elimination. This study
      examines individual respiratory events and relates magnitude of postevent
      ventilation to CO(2) load during the preceding respiratory event in 14 patients
      with OSA (arterial PCO(2) 42-56 Torr). Ventilation and expiratory CO(2) and O(2)
      fractions were measured on a breath-by-breath basis during daytime sleep.
      Calculations included CO(2) load during each event (metabolic CO(2) production -
      exhaled CO(2)) and postevent ventilation in the 10 s after an event. In 12 of 14
      patients, a direct relationship existed between postevent ventilation and CO(2)
      load during the preceding event (P < 0.05); the slope of this relationship varied
      across subjects. Thus the postevent ventilation is tightly linked to CO(2)
      loading during each respiratory event and may be an important mechanism that
      defends against development of acute hypercapnia in OSA. An inverse relationship
      was noted between this postevent ventilatory response slope and the chronic awake
      arterial PCO(2) (r = 0.90, P < 0.001), suggesting that this mechanism is impaired
      in patients with chronic hypercapnia. The link between development of acute
      hypercapnia during respiratory events asleep and maintenance of chronic awake
      hypercapnia in OSA remains to be further investigated.

PMID- 12183488
TI  - Differential changes of lung diffusing capacity and tissue volume in
      hypergravity.
AB  - In normal gravity, lung diffusing capacity (DL(CO)) and lung tissue volume (LTV;
      including pulmonary capillary blood volume) change in concert, for example,
      during shifts between upright and supine. Accordingly, DL(CO) and LTV might be
      expected to decrease together in sitting subjects in hypergravity due to
      peripheral pooling of blood and reduced central blood volume. Nine sitting
      subjects in a human centrifuge were exposed to one, two, and three times
      increased gravity in the head-to-feet direction (G(z+)) and rebreathed a gas
      containing trace amounts of acetylene and carbon monoxide. DL(CO) was 25.2 +/-
      2.6, 20.0 +/- 2.1, and 16.7 +/- 1.7 ml. min(-1). mbar(-1) (means +/- SE) at 1, 2,
      and 3 G(z+), respectively (ANOVA P < 0.001). Corresponding values for LTV
      increased from 541 +/- 34 to 677 +/- 43, and 756 +/- 71 ml (P < 0.001) at 2 and 3
      G(z+). Results are compatible with sequestration of blood in the dependent part
      of the pulmonary circulation just as in the systemic counterpart. DL(CO,) which
      under normoxic conditions is mainly determined by its membrane component,
      decreased despite an increased pulmonary capillary blood volume, most likely as a
      consequence of a less homogenous distribution of alveolar volume with respect to
      pulmonary capillary blood volume.

PMID- 12183489
TI  - Serotonergic modulation of respiratory motor output during tadpole development.
AB  - To test the hypothesis that serotonin (5-hydroxytryptamine; 5-HT)-receptor
      activation elicits age-dependent changes in respiratory motor output, we compared
      the effects of 5-HT bath application (5-HT concentration = 0.5-25 microM) onto in
      vitro brain stem preparations from pre- and postmetamorphic bullfrog tadpoles.
      Recording of motor output related to gill and lung ventilation showed that 5-HT
      elicits a dose-dependent depression of gill burst frequency in both groups. In
      contrast, the lung burst frequency response was stage dependent; an increase in
      lung burst frequency at low 5-HT concentration (< or =0.5 microM) was observed
      only in the postmetamorphic group. Higher 5-HT concentrations decreased lung
      burst frequency in all preparations. Gill burst frequency attenuation is mediated
      (at least in part) by 5-HT(1A)-receptor activation in an age-dependent fashion.
      We conclude that serotonergic modulation of respiratory motor output 1) changes
      during tadpole development and 2) is distinct for gill and lung ventilation.

PMID- 12183490
TI  - Time course of performance changes and fatigue markers during intensified
      training in trained cyclists.
AB  - To study the cumulative effects of exercise stress and subsequent recovery on
      performance changes and fatigue indicators, the training of eight endurance
      cyclists was systematically controlled and monitored for a 6-wk period. Subjects
      completed 2 wk of normal (N), intensified (ITP), and recovery training. A
      significant decline in maximal power output (N = 338 +/- 17 W, ITP = 319 +/- 17
      W) and a significant increase in time to complete a simulated time trial (N =
      59.4 +/- 1.9 min, ITP = 65.3 +/- 2.6 min) occurred after ITP in conjunction with
      a 29% increase in global mood disturbance. The decline in performance was
      associated with a 9.3% reduction in maximal heart rate, a 5% reduction in maximal
      oxygen uptake, and an 8.6% increase in perception of effort. Despite the large
      reductions in performance, no changes were observed in substrate utilization,
      cycling efficiency, and lactate, plasma urea, ammonia, and catecholamine
      concentrations. These findings indicate that a state of overreaching can already
      be induced after 7 days of intensified training with limited recovery.

PMID- 12183491
TI  - Delayed rectifier potassium channels contribute to the depressed pulmonary artery
      contractility in pneumonia.
AB  - We investigated the role of K(+) channels in the attenuated pulmonary artery (PA)
      contractility characteristic of acute Pseudomonas pneumonia. Contractility of PA
      rings from the lungs of control or pneumonia rats was assessed in vitro by
      obtaining cumulative concentration-response curves to the contractile agonists
      KCl, phenylephrine, or PGF(2 alpha) on PA rings before and after treatment with
      K(+) channel blockers. In rings from pneumonia rats, paxilline (10 microM),
      tetraethylammonium (2 mM) (blockers of large-conductance Ca(2+)-activated K(+)
      channels), and glybenclamide (ATP-sensitive K(+) channel blocker, 80 microM) had
      no significant effect on the attenuated contractile responses to KCl,
      phenylephrine, and PGF(2 alpha). However, 4-aminopyridine (2 mM), a blocker of
      voltage-gated K(+) channels (delayed rectifier K(+) channel) reversed this
      depressed contractility. Therefore, large-conductance Ca(2+)-activated K(+) and
      ATP-sensitive K(+) channels do not contribute to the attenuated PA contractility
      observed in this model of acute pneumonia. In contrast, 4-aminopyridine enhances
      contraction in PA rings from pneumonia lungs, consistent with involvement of a
      voltage-gated K(+) channel in the depressed PA contractility in acute pneumonia.
      Unraveling the precise mechanism of attenuated contractility in pneumonia could
      lead to innovative therapies for the pulmonary vascular abnormalities associated
      with this disease.

PMID- 12183492
TI  - Stimulation of regional lymphatic and blood flow by epicutaneous oxazolone.
AB  - The application of the epicutaneous antigen oxazolone results in persistent
      induration and erythema; however, the relative changes in lymph and blood flow in
      the inflammatory skin are largely unknown. To define the contribution of lymph
      and blood flow to the clinical appearance of cutaneous inflammation, we studied
      the sheep ear after the application of oxazolone. As a model for the study of
      these changes, the sheep ear had several experimental advantages: 1) a simplified
      superficial vascular network, 2) defined lymphatic drainage, and 3) an avascular
      and alymphatic cartilaginous barrier. Lymph flow was continuously monitored by
      cannulation of the prescapular efferent lymph duct. Blood flow, as reflected by
      cutaneous erythema, was noninvasively measured by use of a visible-spectrum
      spectrophotometer. The application of the epicutaneous oxazolone resulted in
      increased ear thickness for >7 days. The lymph flow from the oxazolone-stimulated
      ear peaked between 24 and 48 h after oxazolone stimulation. Spectrophotometric
      evaluation indicated that the cutaneous erythema peaked 72-96 h after application
      of oxazolone. Corrosion casting and scanning electron microscopy of the
      microcirculation at 96 h after antigen stimulation demonstrated significant
      dilatation of the superficial vascular network. These results suggest a biphasic
      response to oxazolone stimulation: 1) an early increase in vascular permeability
      associated with increased lymph flow and 2) a subsequent increase in relative
      blood flow associated with a dilated inflammatory microcirculation.

PMID- 12183493
TI  - Ventilatory phenotypes among four strains of adult rats.
AB  - Our purpose in this study was to identify different ventilatory phenotypes among
      four different strains of rats. We examined 114 rats from three in-house, inbred
      strains and one outbred strain: Brown Norway (BN; n = 26), Dahl salt-sensitive (n
      = 24), Fawn-hooded Hypertensive (FHH: n = 27), and outbred Sprague-Dawley rats
      (SD; n = 37). We measured eupneic (room air) breathing and the ventilatory
      responses to hypoxia (12% O(2)-88% N(2)), hypercapnia (7% CO(2)), and two levels
      of submaximal exercise. Primary strain differences were between BN and the other
      strains. BN rats had a relatively attenuated ventilatory response to CO(2) (P <
      0.001), an accentuated ventilatory response to exercise (P < 0.05), and an
      accentuated ventilatory roll-off during hypoxia (P < 0.05). Ventilation during
      hypoxia was lower than other strains, but hyperventilation during hypoxia was
      equal to the other strains (P > 0.05), indicating that the metabolic rate during
      hypoxia decreased more in BN rats than in other strains. Another strain
      difference was in the frequency and timing components of augmented breaths, where
      FHH rats frequently differed from the other strains, and the BN rats had the
      longest expiratory time of the augmented breaths (probably secondary to the
      blunted CO(2) sensitivity). These strain differences not only provide insight
      into physiological mechanisms but also indicate traits (such as CO(2)
      sensitivity) that are genetically regulated. Finally, the data establish a
      foundation for physiological genomic studies aimed at elucidating the genetics of
      these ventilatory control mechanisms.

PMID- 12183494
TI  - L-NAME differentially alters ventilatory behavior in Sprague-Dawley and Brown
      Norway rats.
AB  - Nitric oxide (NO) is a regulating factor in respiration. The question was whether
      NO synthase (NOS) blockade would affect posthypoxic ventilatory behavior
      similarly in two rat strains with known differences in steady-state hypoxic and
      hypercapnic responses and in posthypoxic ventilatory behavior. Ventilatory
      behavior [respiratory frequency (f) and minute ventilation (VE)] was measured by
      body plethysmography on unanesthetized, unrestrained adult male Sprague-Dawley
      (SD; n = 8) and Brown Norway rats (BN; n = 8) at baseline and 1 min after rapid
      transition to 100% O(2) after 5 min of isocapnic hypoxia (10% O(2)-3% CO(2)
      balance N(2)). Testing was performed 30 min after intraperitoneal injection of
      either saline (vehicle) or 100 mg/kg of N(G)-nitro-L-arginine methyl ester (L
      NAME). Resting f and VE increased after L-NAME in both strains, more markedly in
      SD compared with BN (77 vs. 47% for f, and 42 vs. 16% for VE, respectively; P <
      0.05). With vehicle, posthypoxic f and VE decline (Dejours phenomenon) was
      present only in BN and was absent in SD. With L-NAME, the Dejours phenomena were
      still present in BN but also were apparent in SD (f: 95.3 vs. 134.4 beats/min at
      baseline; VE: 66.3 vs. 88.8 ml/min at baseline; P < 0.05). Thus NOS blockade
      results in a strain-specific alteration in resting ventilation and uncovers the
      Dejours phenomenon in the SD strain.

PMID- 12183495
TI  - Effect of different protocols of caffeine intake on metabolism and endurance
      performance.
AB  - Competitive athletes completed two studies of 2-h steady-state (SS) cycling at
      70% peak O(2) uptake followed by 7 kJ/kg time trial (TT) with carbohydrate (CHO)
      intake before (2 g/kg) and during (6% CHO drink) exercise. In Study A, 12
      subjects received either 6 mg/kg caffeine 1 h preexercise (Precaf), 6 x 1 mg/kg
      caffeine every 20 min throughout SS (Durcaf), 2 x 5 ml/kg Coca-Cola between 100
      and 120 min SS and during TT (Coke), or placebo. Improvements in TT were as
      follows: Precaf, 3.4% (0.2-6.5%, 95% confidence interval); Durcaf, 3.1% (-0.1
      6.5%); and Coke, 3.1% (-0.2-6.2%). In Study B, eight subjects received 3 x 5
      ml/kg of different cola drinks during the last 40 min of SS and TT:
      decaffeinated, 6% CHO (control); caffeinated, 6% CHO; decaffeinated, 11% CHO; and
      caffeinated, 11% CHO (Coke). Coke enhanced TT by 3.3% (0.8-5.9%), with all trials
      showing 2.2% TT enhancement (0.5-3.8%; P < 0.05) due to caffeine. Overall, 1) 6
      mg/kg caffeine enhanced TT performance independent of timing of intake and 2)
      replacing sports drink with Coca-Cola during the latter stages of exercise was
      equally effective in enhancing endurance performance, primarily due to low intake
      of caffeine (approximately 1.5 mg/kg).

PMID- 12183496
TI  - Major gene effects on exercise ventilatory threshold: the HERITAGE Family Study.
AB  - This study investigates whether there are major gene effects on oxygen uptake at
      the ventilatory threshold (VO(2VT)) and the VO(2VT) maximal oxygen uptake
      (VT%VO(2 max)), at baseline and in response to 20 wk of exercise training by
      using data on 336 whites and 160 blacks. Segregation analysis was performed on
      the residuals of VO(2VT) and VT%VO(2 max). In whites, there was strong evidence
      of a major gene, with 3 and 2% of the sample in the upper distribution, that
      accounted for 52 and 43% of the variance in baseline VO(2VT) and VT%VO(2 max),
      respectively. There were no genotype-specific covariate effects (sex, age,
      weight, fat mass, and fat-free mass). The segregation results were inconclusive
      for the training response in whites, and for the baseline and training response
      in blacks, probably due to insufficient power because of reduced sample sizes or
      smaller gene effect or both. The strength of the genetic evidence for VO(2VT) and
      VT%VO(2 max) suggests that these traits should be further investigated for
      potential relations with specific candidate genes, if they can be identified, and
      explored through a genome-wide scan.

PMID- 12183497
TI  - Effect of surface tension and surfactant administration on Eustachian tube
      mechanics.
AB  - Development of otitis media has been related to abnormal Eustachian tube (ET)
      mechanics. ET is a collapsible tube that is periodically opened to regulate
      middle ear pressure and to clear middle ear fluid into the nasopharynx. The
      ability to perform these physiological functions depends on several mechanical
      properties, including the ET's opening pressure (P(open)), compliance (ETC), and
      hysteresis (eta). In this study, a previously developed modified force-response
      protocol was used to determine ET mechanical properties after experimental
      manipulation of the mucosal surface condition. Specifically, these properties
      were measured in the right ear of six cynomologous monkeys under baseline
      conditions after "washing out" the normal ET mucous layer and after instillation
      of a pulmonary surfactant, Infasurf. Removal of the normal mucosa did not
      significantly alter P(open) but did result in a decrease in ETC and eta (P <
      0.05). Treatment of the mucosa with Infasurf was effective in reducing P(open)
      and increasing both ETC and eta to baseline values (P < 0.05). These results
      indicate that the mucosa-air surface tension can affect the overall ETC and eta
      properties of the ET. In addition, this study indicates that surfactant therapy
      may only be beneficial in patients with rigid or inelastic ETs (large P(open) and
      low ETC and eta).

PMID- 12183498
TI  - Effect of surface tension on alveolar surface area.
AB  - At fixed lung volume (VL), alterations in surface tension change alveolar surface
      area (S) and lung recoil (PL). Wilson (26), using data from fixed lungs (1, 9),
      quantified the isovolume change in S with PL. We reexamined this question in
      fresh excised rabbit lungs, with two important differences. First, we measured
      fractional changes in S by using diffuse light scattering, avoiding the potential
      upset of the balance of tissue and surface forces during fixation. Second, we
      altered surface tension by ventilating the lungs with nebulized
      polydimethylsiloxane, with much less residual fluid compared with lavage. We
      found that S decreased at low and mid VL (treatment surface tension > control) by
      about half of Wilson's estimates and was nearly unaffected by treatment at high
      VL. This suggests that with increased surface tension there is 1) greater septal
      retraction in lungs fixed by vascular perfusion compared with unfixed lungs and
      2) a greater increase in PL and less loss of S than would have been predicted.

PMID- 12183499
TI  - Increased surface tension decreases pulmonary capillary volume and compliance.
AB  - Increased surface tension is an important component of several respiratory
      diseases, but its effects on pulmonary capillary mechanics are incompletely
      understood. We measured capillary volume and specific compliance before and after
      increasing surface tension with nebulized siloxane in excised dog lungs. The
      change in surface tension was sufficient to increase lung recoil 5 cm H(2)O at
      50% total lung capacity. Increased surface tension decreased both capillary
      volume and specific compliance. The changes in capillary volume and compliance
      were greatest at the lung volumes at which the surface tension change was
      greatest. Near functional residual capacity, capillary volume postsiloxane was
      approximately 30% of control. Presiloxane capillary specific compliance was
      approximately 7%/cm H(2)O near functional residual capacity and approximately
      2.5%/cm H(2)O near total lung capacity. Postsiloxane capillary-specific
      compliance was 3%/cm H(2)O, and was independent of lung volume. We conclude that
      in addition to their well-known effects on lung mechanics, changes in surface
      tension also have important effects on capillary mechanics. We speculate that
      these changes may in turn affect ventilation and perfusion, worsen gas exchange,
      and alter leukocyte sequestration.

PMID- 12183500
TI  - Volume-dependent variations of regional lung sound, amplitude, and phase.
AB  - Acoustic imaging of the respiratory system demonstrates regional changes of lung
      sounds that correspond to pulmonary ventilation. We investigated volume-dependent
      variations of lung sound phase and amplitude between two closely spaced sensors
      in five adults. Lung sounds were recorded at the posterior right upper, right
      lower, and left lower lobes during targeted breathing (1.2 +/- 0.2 l/s; volume =
      20-50 and 50-80% of vital capacity) and passive sound transmission (< or =0.2
      l/s; volumes as above). Average sound amplitudes were obtained after band-pass
      filtering to 75-150, 150-300, and 300-600 Hz. Cross correlation established the
      phase relation of sound between sensors. Volume-dependent variations in phase (<
      or =1.5 ms) and amplitude (< or =11 dB) were observed at the lower lobes in the
      150- to 300-Hz band. During inspiration, increasing delay and amplitude of sound
      at the caudal relative to the cranial sensor were also observed during passive
      transmission in several subjects. This previously unrecognized behavior of lung
      sounds over short distances might reflect spatial variations of airways and
      diaphragms during breathing.

PMID- 12183501
TI  - Energy cost of walking and running at extreme uphill and downhill slopes.
AB  - The costs of walking (Cw) and running (Cr) were measured on 10 runners on a
      treadmill inclined between -0.45 to +0.45 at different speeds. The minimum Cw was
      1.64 +/- 0.50 J. kg(-1). m(-1) at a 1.0 +/- 0.3 m/s speed on the level. It
      increased on positive slopes, attained 17.33 +/- 1.11 J. kg(-1). m(-1) at +0.45,
      and was reduced to 0.81 +/- 0.37 J. kg(-1). m(-1) at -0.10. At steeper slopes, it
      increased to reach 3.46 +/- 0.95 J. kg(-1). m(-1) at -0.45. Cr was 3.40 +/- 0.24
      J. kg(-1). m(-1) on the level, independent of speed. It increased on positive
      slopes, attained 18.93 +/- 1.74 J. kg(-1). m(-1) at +0.45, and was reduced to
      1.73 +/- 0.36 J. kg(-1). m(-1) at -0.20. At steeper slopes, it increased to reach
      3.92 +/- 0.81 J. kg(-1). m(-1) at -0.45. The mechanical efficiencies of walking
      and running above +0.15 and below -0.15 attained those of concentric and
      eccentric muscular contraction, respectively. The optimum gradients for mountain
      paths approximated 0.20-0.30 for both gaits. Downhill, Cr was some 40% lower than
      reported in the literature for sedentary subjects. The estimated maximum running
      speeds on positive gradients corresponded to those adopted in uphill races; on
      negative gradients they were well above those attained in downhill competitions.

PMID- 12183502
TI  - Spaceflight affects bone formation in rhesus monkeys: a histological and cell
      culture study.
AB  - Using analyses of iliac crest cell and tissue, back-scattered electron imaging,
      and biochemical techniques, we characterized the effects of a 14-day spaceflight
      (Bion 11) on bone structure and bone formation in two 3- to 4-yr-old male rhesus
      monkeys compared with eight age-matched Earth-control monkeys. We found that
      postflight bone volume was 35% lower than preflight values in flight monkeys.
      This was associated with reduced osteoid (-40%) and mineralizing (-32%) surfaces
      and decreased bone formation rate (-53%). Moreover, flight monkeys exhibited
      trends to lower values of mineralization profile in iliac bone (back-scattered
      electron imaging) and to decreased osteocalcin serum levels (P = 0.08). The
      initial number of trabecular bone cells yielded in cultures did not differ in
      flight and control animals before or after the flight. However, osteoblastic cell
      proliferation was markedly lower in postflight vs. preflight at 9 and 14 days of
      culture in one flight monkey. This study suggests that a 14-day spaceflight
      reduces iliac bone formation, osteoblastic activity, and/or recruitment in young
      rhesus monkeys, resulting in decreased trabecular bone volume.

PMID- 12183503
TI  - Sex differences in hepatic gene expression in a rat model of ethanol-induced
      liver injury.
AB  - Sex differences in susceptibility to alcohol-induced liver injury have been
      observed in both humans and experimental animal models. Using a standard model of
      alcohol-induced fatty liver injury and microarray analysis, we have identified
      differential expression of hepatic genes in both sexes. The genes that exhibit
      differential expression are of three types: those that are changed only in male
      rats fed alcohol, those that change in only female rats fed alcohol, and those
      that change in both sexes, although not always in the same manner. Certain of the
      differentially expressed genes have previously been identified as participants in
      the induction of alcohol-induced liver injury. However, this analysis has
      identified a number of genes that heretofore have not been implicated in
      alcoholic liver injury; such genes may provide new areas of investigation into
      the pathogenesis of this disease.

PMID- 12183504
TI  - Volume history and effect on airway reactivity in infants and adults.
AB  - Volume history is an important determinant of airway responsiveness. In healthy
      adults undergoing airway challenge, deep inspiration (DI) provides
      bronchodilating and bronchoprotective effects; however, the effectiveness of DI
      is limited in asthmatic adults. We hypothesized that, when assessed under similar
      conditions, healthy infants have heightened airway reactivity compared with
      healthy adults and that the effectiveness of DI is limited in infants. We
      compared the effect of DI on reactivity by using full (DI) vs. partial (no DI)
      forced-expiratory maneuvers on 2 days in supine, healthy nonasthmatic infants
      (21) and adults (10). Reactivity was assessed by methacholine doses that
      decreased forced expiratory flow after exhalation of 75% forced vital capacity
      during a full maneuver and maximal expiratory flow at functional residual
      capacity during a partial maneuver by 30% from baseline. Reactivity in adults
      increased when DI was absent, whereas infants' reactivity was unchanged. Infants
      were more reactive than adults in the presence of DI; however, adult and infant
      reactivity was similar in its absence. Our findings indicate that healthy infants
      are more reactive than adults and, like asthmatic adults, do not benefit from DI;
      this difference may be an important characteristic of airway hyperreactivity.

PMID- 12183505
TI  - Smaller muscle ATP reduction in women than in men by repeated bouts of sprint
      exercise.
AB  - It was hypothesized that the reduction of high-energy phosphates in muscle after
      repeated sprints is smaller in women than in men. Fifteen healthy and physically
      active women and men with an average age of 25 yr (range of 19-42 yr) performed
      three 30-s cycle sprints (Wingate test) with 20 min of rest between sprints.
      Repeated blood and muscle samples were obtained. Freeze-dried pooled muscle
      fibers of types I and II were analyzed for high-energy phosphates and their
      breakdown products and for glycogen. Accumulation of plasma ATP breakdown
      products, plasma catecholamines, and blood lactate, as well as glycogen reduction
      in type I fibers, was all lower in women than in men during sprint exercise.
      Repeated sprints induced smaller reduction of ATP and smaller accumulation of IMP
      and inosine in women than in men in type II muscle fibers, with no gender
      differences in changes of ATP and its breakdown products during the bouts of
      exercise themselves. This indicates that the smaller ATP reduction in women than
      in men during repeated sprints was created during recovery periods between the
      sprint exercises and that women possess a faster recovery of ATP via reamination
      of IMP during these recovery periods.

PMID- 12183506
TI  - A mathematical model to detect inspiratory flow limitation during sleep.
AB  - The physiological significance of inspiratory flow limitation (IFL) has recently
      been recognized, but methods of detecting IFL can be subjective. We sought to
      develop a mathematical model of the upper airway pressure-flow relationship that
      would objectively detect flow limitation. We present a theoretical discussion
      that predicts that a polynomial function [F(P) = AP(3) + BP(2) + CP + D, where
      F(P) is flow and P is supraglottic pressure] best characterizes the pressure-flow
      relationship and allows for the objective detection of IFL. In protocol 1, step
      1, we performed curve-fitting of the pressure-flow relationship of 20 breaths to
      5 mathematical functions and found that highest correlation coefficients (R(2))
      for quadratic (0.88 +/- 0.10) and polynomial (0.91 +/- 0.05; P < 0.05 for both
      compared with the other functions) functions. In step 2, we performed error-fit
      calculations on 50 breaths by comparing the quadratic and polynomial functions
      and found that the error fit was lowest for the polynomial function (3.3 +/- 0.06
      vs. 21.1 +/- 19.0%; P < 0.001). In protocol 2, we performed
      sensitivity/specificity analysis on two sets of breaths (50 and 544 breaths) by
      comparing the mathematical determination of IFL to manual determination.
      Mathematical determination of IFL had high sensitivity and specificity and a
      positive predictive value (>99% for each). We conclude that a polynomial function
      can be used to predict the relationship between pressure and flow in the upper
      airway and objectively determine the presence of IFL.

PMID- 12183507
TI  - Muscle activity damps the soft tissue resonance that occurs in response to pulsed
      and continuous vibrations.
AB  - This study tested the hypotheses that when the excitation frequency of mechanical
      stimuli to the foot was close to the natural frequency of the soft tissues of the
      lower extremity, the muscle activity increases 1) the natural frequency and 2)
      the damping to minimize resonance. Soft tissue vibrations were measured with
      triaxial accelerometers, and muscle activity was measured by using surface
      electromyography from the quadriceps, hamstrings, tibialis anterior, and triceps
      surae groups from 20 subjects. Subjects were presented vibrations while standing
      on a vibrating platform. Both continuous vibrations and pulsed bursts of
      vibrations were presented, across the frequency range of 10-65 Hz. Elevated
      muscle activity and increased damping of vibration power occurred when the
      frequency of the input was close to the natural frequency of each soft tissue.
      However, the natural frequency of the soft tissues did not change in a manner
      that correlated with the frequency of the input. It is suggested that soft tissue
      damping may be the mechanism by which resonance is minimized at heel strike
      during running.

PMID- 12183508
TI  - Tracer kinetic model of regional pulmonary function using positron emission
      tomography.
AB  - To determine the spatial distributions of pulmonary perfusion, shunt, and
      ventilation, we developed a compartmental model of regional (13)N-labeled
      molecular nitrogen ((13)NN) kinetics measured from positron emission tomography
      (PET) images. The model features a compartment for right heart and pulmonary
      vasculature and two compartments for each region of interest: 1) aerated alveolar
      units and 2) alveolar units with no gas content (shunting). The model was tested
      on PET data from normal animals (dogs and sheep) and from animals with
      experimentally injured lungs simulating acute respiratory distress syndrome. The
      analysis yielded estimates of regional perfusion, shunt fraction, and specific
      ventilation with excellent goodness-of-fit to the data (R(2) > 0.99). Model
      parameters were estimated to within 10% accuracy in the presence of exaggerated
      levels of experimental noise by using a Monte Carlo sensitivity analysis. Main
      advantages of the present model are that 1) it separates intraregional blood flow
      to aerated alveolar units from that shunting across nonaerated units and 2) it
      accounts and corrects for intraregional tracer removal by shunting blood when
      estimating ventilation from subsequent washout of tracer. The model was thus
      found to provide estimates of regional parameters of pulmonary function in sizes
      of lung regions that could potentially approach the intrinsic resolution for PET
      images of (13)NN in lung (approximately 7.0 mm for a multiring PET camera).

PMID- 12183509
TI  - Alterations in regional ventilation, perfusion, and shunt after smoke inhalation
      measured by PET.
AB  - Regional changes in ventilation and perfusion occurring in the early hours after
      smoke inhalation injury were evaluated through the use of positron emission
      tomography. Five lambs were imaged before and 1, 2, and 4 h after receiving 100
      breaths of cotton smoke. Utilizing a recently developed model of (13)N tracer
      kinetics (3), we evaluated changes in ventilation, perfusion, shunt, and regional
      gas content in nondependent, middle, and dependent lung zones. The data
      demonstrated a progressive development of regional shunt in dependent (dorsal)
      regions in which perfusion remained the highest throughout the study. These
      findings, together with decreasing regional ventilation and fractional gas
      content in the dependent regions, correlated with decreasing arterial Pa(O(2))
      values over the course of the study. A negative correlation between regional
      shunt fraction and regional gas content in dependent and middle regions suggests
      that shunt was caused by progressive alveolar derecruitment or flooding.

PMID- 12183510
TI  - Regulation of TGF-beta ligand and receptor expression in neonatal rat lungs
      exposed to chronic hypoxia.
AB  - Long-term effects of hypoxia are largely due to its modulatory effects on
      proliferation and differentiation of epithelial and endothelial cells, processes
      also regulated by the transforming growth factor (TGF)-beta system. We
      investigated the effects of hypoxia on the TGF-beta system in rat lungs from
      different developmental stages. Sprague-Dawley rats were exposed to 9.5% oxygen
      during either the first 2 wk of life or adulthood. Analysis revealed an arrest of
      alveolarization in hypoxic postnatal day 14 rats. Bioactive TGF-beta levels in
      bronchoalveolar lavage fluid were increased in these animals, and Western blot
      analysis revealed upregulation of TGF-beta receptor (TbetaR) I and II. None of
      these changes was observed in hypoxic adults. Hypoxia did, however, lead to
      decreased expression of TbetaRIII in both postnatal day 14 and adult rats.
      Immunohistochemical analysis localized TbetaRI-III predominantly to bronchiolar
      and alveolar epithelium; these patterns did not change with hypoxia. Thus we
      observed changes in TGF-beta activity and TbetaR isotype expression in rat lung
      that parallel the arrest in alveolarization seen with chronic hypoxia in early
      development. These alterations may partly explain the morphological changes
      observed in hypoxia.

PMID- 12183511
TI  - Angiopoietin-2 and rat brain capillary remodeling during adaptation and
      deadaptation to prolonged mild hypoxia.
AB  - Angiogenesis is a crucial component of rat brain adaptation to prolonged hypoxia,
      but it is not known whether this structural change is permanent or reversed on
      return to normoxia. Also, the intrinsic mechanisms controlling brain
      microvascular plasticity in response to oxygen availability remains unclear. Our
      results indicate that capillary density in the rat cerebral cortex increased by
      60% after 3 wk of hypoxia and that it progressively decreased to prehypoxic
      values after 3 wk of normoxic recovery (deadaptation). Angiopoietin-2 (Ang2)
      expression in the capillary endothelium was induced between 6 h and 14 days of
      hypoxia but fell to control levels at 21 days of hypoxia. During deadaptation,
      Ang2 levels were elevated at 1-14 days but decreased to baseline at 21 days. In
      contrast, the constitutive expression of Ang1 and Tie2 was not affected during
      hypoxia or deadaptation. TUNEL-positive endothelial cells and caspase-3
      activation were observed at 7 and 14 days of deadaptation. These data suggest
      that Ang2 might modulate both angiogenesis and vascular regression in the rat
      brain and that capillary regression occurring during deadaptation involves
      activation of apoptosis.

PMID- 12183512
TI  - VEGF enhances functional improvement of postinfarcted hearts by transplantation
      of ESC-differentiated cells.
AB  - Despite considerable advances in medicine, the incidence of heart failure remains
      high in patients after myocardial infarction (MI). This study investigated the
      effects of engrafted early-differentiated cells (EDCs) from mouse embryonic stem
      cells, with or without transfection of vascular endothelial growth factor (VEGF)
      cDNA (phVEGF(165)), on cardiac function in postinfarcted mice. EDCs were
      transfected with green fluorescent protein (GFP) cDNA and transplanted into
      infarcted myocardium. Compared with the MI mice receiving cell-free medium,
      cardiac function was significantly improved in the MI mice 6 wk after
      transplantation of EDCs. Moreover, improvement of heart function was
      significantly greater in the mice implanted with EDCs overexpressing VEGF (EDCs
      VEGF) than with EDCs alone. Frozen sections of infarcted myocardium with EDCs or
      EDCs-VEGF transplantation showed GFP-positive tissue. The area with positive
      immunostaining for cardiac troponin I and alpha-myosin heavy chain was larger in
      injured myocardium with EDCs or EDCs-VEGF transplantation than with medium
      injection. Transplantation of EDCs or EDCs-VEGF significantly increased the
      number of blood vessels in the MI area. However, the density of capillaries was
      significantly higher in the EDCs-VEGF animals than in the EDC mice. Double
      staining for GFP and connexin-43 was positive in injured myocardium with EDC
      transplantation. Our data demonstrate that engrafted EDCs or EDCs-VEGF
      regenerated cardiac tissue and significantly improved cardiac function in
      postinfarcted hearts. The novel EDCs-VEGF synergistic approach may have an
      important impact on future cell therapy for patients experiencing MI or heart
      failure.

PMID- 12183513
TI  - Effects of tower climbing exercise on bone mass, strength, and turnover in
      orchidectomized growing rats.
AB  - To determine the effects of a tower climbing exercise on mass, strength, and
      local turnover of bone, 70 9-wk-old Sprague-Dawley rats were assigned to seven
      groups: a baseline control and three groups of sham-operated sedentary,
      orchidectomized (ORX)-sedentary and ORX-exercise rats. Rats voluntarily climbed a
      200-cm tower to drink water from a bottle set at the top. At 4 wk, the periosteal
      bone formation rate (BFR), moment of inertia, bone mineral content, bone mineral
      density, and bending load at the midfemur were maintained in ORX-exercise rats,
      whereas these parameters were reduced in ORX-sedentary rats. At 8 wk, the
      periosteal mineral apposition rate and BFR in ORX-exercise rats were
      significantly higher, whereas the parameters in ORX-sedentary rats did not differ
      compared with sham-sedentary rats. In ORX-exercise rats, the trabecular
      mineralizing surface, BFR, and bone volume of the lumbar vertebrae were
      maintained at the same levels as those in the sham-sedentary group, whereas the
      osteoclast surface decreased compared with the ORX-sedentary group. However, the
      climbing exercise did not affect bone mineral content, bone mineral density, or
      the compression load of the lumbar vertebrae. These results show that, in the
      midfemur, the voluntary climbing exercise maintained cortical bone mass and
      strength by stimulating periosteal bone formation and partially prevented ORX
      induced trabecular bone loss, depressing the elevation of turnover.
      Interestingly, in ORX rats, the climbing exercise had the opposite effect on bone
      formation at the periosteal femoral cortical bone, where the exercise increased
      the bone formation compared with vertebral trabecular bone, where the exercise
      decreased it.

PMID- 12183514
TI  - Invited Review: Autocrine/paracrine IGF-I and skeletal muscle adaptation.
AB  - This brief review presents the basic premises suggesting that insulin-like growth
      factor I (IGF-I), functioning in an autocrine/paracrine mode, is an important
      mediator of skeletal muscle adaptation. Key intracellular signaling mechanisms
      associated with ligation of the primary IGF-I receptor are highlighted to
      illustrate the mechanisms by which IGF-I may promote muscle hypertrophy. In
      addition, a number of recent findings are presented that highlight the potential
      for interactions between IGF-I-related signaling pathways and intracellular
      signaling mechanisms activated by cytokines or hormonal systems.

PMID- 12183515
TI  - Invited Review: Role of insulin in translational control of protein synthesis in
      skeletal muscle by amino acids or exercise.
AB  - Protein synthesis in skeletal muscle is modulated in response to a variety of
      stimuli. Two stimuli receiving a great deal of recent attention are increased
      amino acid availability and exercise. Both of these effectors stimulate protein
      synthesis in part through activation of translation initiation. However, the full
      response of translation initiation and protein synthesis to either effector is
      not observed in the absence of a minimal concentration of insulin. The
      combination of insulin and either increased amino acid availability or endurance
      exercise stimulates translation initiation and protein synthesis in part through
      activation of the ribosomal protein S6 protein kinase S6K1 as well as through
      enhanced association of eukaryotic initiation factor eIF4G with eIF4E, an event
      that promotes binding of mRNA to the ribosome. In contrast, insulin in
      combination with resistance exercise stimulates translation initiation and
      protein synthesis through enhanced activity of a guanine nucleotide exchange
      protein referred to as eIF2B. In both cases, the amount of insulin required for
      the effects is low, and a concentration of the hormone that approximates that
      observed in fasting animals is sufficient for maximal stimulation. This review
      summarizes the results of a number of recent studies that have helped to
      establish our present understanding of the interactions of insulin, amino acids,
      and exercise in the regulation of protein synthesis in skeletal muscle.

PMID- 12183516
TI  - Susceptibility of interleukin-2-deficient mice to Toxoplasma gondii is associated
      with a defect in the production of gamma interferon.
AB  - Costimulation through the B7-CD28 interaction is an important second signal for T
      cell activation, and previous studies have shown that CD28(-/-) mice infected
      with Toxoplasma gondii generate suboptimal CD4(+) T-cell responses, associated
      with a defect in production of the T-cell growth factor interleukin-2 (IL-2). To
      address the role of IL-2 in the expansion of T cells during toxoplasmosis, IL-2(
      /-) mice were infected with T. gondii and their ability to generate a protective
      T-cell response was assessed. Although IL-2(-/-) mice produced normal levels of
      IL-12p40, they had reduced levels of gamma interferon (IFN-gamma) in serum, had
      an increased parasite burden, and succumbed to infection with T. gondii within 20
      days. Fluorescence-activated cell sorter analysis revealed that, although
      uninfected IL-2(-/-) mice had an increased number of activated T cells compared
      with uninfected IL-2(+/+) mice, following infection they were unable to further
      upregulate this population. Examination of the ability of splenocytes from
      uninfected and infected mice to produce IFN-gamma revealed that IL-2(-/-) mice
      were hyporesponsive to stimulation with anti-CD3 or parasite antigen compared
      with wild-type mice, and the addition of IL-2 alone or in combination with IL-12
      or stimulation with phorbol myristate acetate and ionomycin did not restore the
      production of IFN-gamma. Together, these studies reveal that IL-2(-/-) mice are
      unable to generate a protective IFN-gamma response following infection with T.
      gondii and suggest that IL-2(-/-) mice have an intrinsic defect in their ability
      to activate and expand IFN-gamma-producing T cells required for resistance to T.
      gondii.

PMID- 12183517
TI  - Cryptococcal glucuronoxylomannan inhibits adhesion of neutrophils to stimulated
      endothelium in vitro by affecting both neutrophils and endothelial cells.
AB  - Cryptococcal infections are often characterized by a paucity of leukocytes in the
      infected tissues. Previous research has shown that the capsular polysaccharide
      glucuronoxylomannan (GXM) inhibits leukocyte migration. In this study we
      investigated whether the capsular polysaccharide GXM affects the migration of
      neutrophils (polymorphonuclear leukocytes [PMN]) through the endothelium by
      interfering with adhesion in a static adhesion model. Pretreatment of PMN with
      GXM inhibited PMN adhesion to tumor necrosis factor alpha (TNF-alpha)-stimulated
      endothelium up to 44%. Treatment of TNF-alpha-stimulated endothelium with GXM led
      to a 27% decrease in PMN adhesion. GXM treatment of both PMN and endothelium did
      not have an additive inhibitory effect. We demonstrated that GXM-induced L
      selectin shedding does not play an important role in the detected inhibition of
      adhesion. L-selectin was still present on PMN in sufficient amounts after GXM
      treatment, since it could be further inhibited by blocking antibodies.
      Furthermore, blocking of GXM-related L-selectin shedding did not abolish the GXM
      related inhibition of adhesion. GXM most likely exerts its effect on PMN by
      interfering with E-selectin-mediated binding. The use of blocking monoclonal
      antibodies against E-selectin, which was shown to decrease adhesion in the
      absence of GXM, did not cause additive inhibition of PMN adhesion after GXM
      pretreatment. The use of blocking antibodies also demonstrated that the
      inhibiting effect found after GXM treatment of endothelium probably involves
      interference with both intercellular adhesion molecule-1 and E-selectin binding.

PMID- 12183518
TI  - Role of the htrA gene in Klebsiella pneumoniae virulence.
AB  - We recently described the use of mini-Tn5 to generate complement-sensitive
      mutants derived from a complement-resistant Klebsiella pneumoniae clinical
      isolate deficient in the lipopolysaccharide O side chain. One mutant with a
      reduced capacity to survive in nonimmune human sera carried the transposon
      inserted in the htrA gene. We cloned and sequenced the gene and predicted from
      the deduced amino acid sequence that the putative HtrA homolog contains
      structural features similar to those of previously described HtrA proteins. To
      investigate the biological functions and the role of the htrA gene in the
      virulence of K. pneumoniae, we constructed an isogenic mutant by insertion
      duplication mutagenesis. Characterization of the mutant showed that it had
      greater sensitivity to temperature (50 degrees C) and oxidative stress (H(2)O(2))
      than the parent strain. Furthermore, the htrA mutant produced less capsule, bound
      more molecules of complement component C3, and was more sensitive to complement
      and whole-blood killing than was the parent strain. Finally, disruption of the
      htrA gene in a virulent K. pneumoniae strain caused a reduction of its virulence
      in a mice model. Our results indicate that the htrA gene plays an important role
      in the virulence of K. pneumoniae.

PMID- 12183519
TI  - Human salivary histatin 5 causes disordered volume regulation and cell cycle
      arrest in Candida albicans.
AB  - Human salivary histatin 5 (Hst 5) is a nonimmune salivary protein with antifungal
      activity against an important human pathogen, Candida albicans. The candidacidal
      activity of histatins appears to be a distinctive multistep mechanism involving
      depletion of the C. albicans intracellular ATP content as a result of nonlytic
      ATP efflux. Hst 5 caused a loss of cell viability concomitant with a decrease in
      cellular volume as determined both by a classical candidacidal assay with
      exogenous Hst 5 and by using a genetically engineered C. albicans strain
      expressing Hst 5. Preincubation of C. albicans cells with pharmacological
      inhibitors of anion transport provided complete or substantial protection from
      Hst 5-induced killing and volume reduction of cells. Moreover, intracellular
      expression of Hst 5 resulted in a reduction in the population mean cell volume
      that was accompanied by an increase in the percentage of unbudded cells and C.
      albicans cells in the G(1) phase. Following expression of Hst 5, the smallest
      cells sorted by fluorescence-activated cell sorting from the total population did
      not replicate and were exclusively in the G(1) phase. Cells with intracellularly
      expressed Hst 5 had greatly reduced G(1) cyclin transcript levels, indicating
      that they arrested in the G(1) phase before the onset of Start. Our data
      demonstrate that a key determinant in the mechanism of Hst 5 toxicity in C.
      albicans cells is the disruption of regulatory circuits for cell volume
      homeostasis that is closely coupled with loss of intracellular ATP. This novel
      process of fungicidal activity by a human salivary protein has highlighted
      potential interactions of Hst 5 with volume regulatory mechanisms and the process
      of yeast cell cycle control.

PMID- 12183520
TI  - Enhancement of protective efficacy following intranasal immunization with vaccine
      plus a nontoxic LTK63 mutant delivered with nanoparticles.
AB  - Most vaccines are still given parenterally. Mucosal vaccination would offer
      different advantages over parenteral immunization, including blocking of the
      pathogens at the portal of entry. In this paper, nontoxic Escherichia coli heat
      labile enterotoxin (LT) mutants and Supramolecular Biovector systems (SMBV) were
      evaluated in mice as mucosal adjuvants and delivery systems, respectively, for
      intranasal immunization with the conjugated group C meningococcal vaccine. The
      conjugated vaccine formulated together with the LT mutants and the SMBV induced
      very high titers of serum and mucosal antibodies specific for the group C
      meningococcal polysaccharide. This vaccination strategy also induced high titers
      of antibodies with bactericidal activity, which is known to correlate with
      efficacy. Importantly, the mucosal vaccination, but not the conventional
      parenteral vaccination, induced bactericidal antibodies at the mucosal level.
      These data strongly support the feasibility of development of intranasal vaccines
      with an enhanced protective efficacy against meningococci and possibly against
      other encapsulated bacteria.

PMID- 12183521
TI  - Immune cell-mediated protection against vaginal candidiasis: evidence for a major
      role of vaginal CD4(+) T cells and possible participation of other local
      lymphocyte effectors.
AB  - The protective roles of different lymphocyte subsets were investigated in a rat
      vaginal candidiasis model by adoptive transfer of vaginal lymphocytes (VL) or
      sorted, purified CD3(+) T cells, CD4(+) or CD8(+) T cells, or CD3(-) CD5(+) B
      cells from the vaginas of naive or immune rats following three rounds of Candida
      albicans infection. The adoptive transfer of total VL from nonimmune animals did
      not alter the course of vaginal candidiasis of the recipient rats. In contrast,
      the animals receiving total VL or CD3(+) T cells from immune rats showed a highly
      significant acceleration of fungus clearance compared with animals which received
      nonimmune VL. The animals with vaginal CD3(-) CD5(+) B cells transferred from
      immune rats also had fewer Candida CFU than the controls, but fungal clearance
      was significantly retarded with respect to the animals administered immune T
      cells. Sorted, purified CD4(+) and CD8(+) vaginal T cells from immune rats were
      also adoptively transferred to naive animals. Although both populations were seen
      to accelerate the clearance of the fungus from the vagina, CD4(+) T cells were
      much more effective than CD8(+) T cells. Overall, there was no difference between
      the antifungal effects of immune vaginal CD4(+) T cells and those achievable with
      the transfer of whole, immune VL. Histological observations of the vaginal
      tissues of rats with adoptively transferred immune T cells demonstrated a
      remarkable accumulation of lymphocytes in the subepithelial lamina propria and
      also infiltrating the mucosal epithelium. These results strongly suggest that
      distinct vaginal lymphocyte subsets participate in the adaptive anti-Candida
      immunity at the vaginal level, with the vaginal CD4(+) T cells probably playing a
      major role.

PMID- 12183522
TI  - Decreased electroporation efficiency in Borrelia burgdorferi containing linear
      plasmids lp25 and lp56: impact on transformation of infectious B. burgdorferi.
AB  - The presence of the linear plasmids lp25 and lp56 of Borrelia burgdorferi B31 was
      found to dramatically decrease the rate of transformation by electroporation with
      the shuttle vector pBSV2, an autonomously replicating plasmid that confers
      kanamycin resistance (P. E. Stewart, R. Thalken, J. L. Bono, and P. Rosa, Mol.
      Microbiol. 39:714-721, 2001). B. burgdorferi B31 clones had transformation
      efficiencies that were either low, intermediate, or high, and this phenotype
      correlated with the presence or absence of lp25 and lp56. Under the conditions
      utilized in this study, no transformants were detected in clones that contained
      both lp25 and lp56; the few kanamycin-resistant colonies isolated did not contain
      pBSV2, indicating that the resistance was due to mutation. Intermediate
      electroporation rates (10 to 200 colonies per micro g of DNA) were obtained with
      B31 clones that were either lp25(-) and lp56(+) or lp25(+) and lp56(-). Clones in
      this group that initially contained lp25 lacked this plasmid in pBSV2
      transformants, a finding consistent with selective transformation of lp25(-)
      variants. High transformation rates (>1,000 colonies per micro g of DNA) occurred
      in clones that lacked both lp25 and lp56. Sequence analysis indicated that lp25
      and lp56 contain genes that may encode restriction and/or modification systems
      that could result in the low transformation rates obtained with strains
      containing these plasmids. The previously reported correlation between lp25 and
      infectivity in mice, coupled with the barrier lp25 presents to transformation,
      may explain the difficulty in obtaining virulent transformants of B. burgdorferi.

PMID- 12183523
TI  - Comparison of host resistance to primary and secondary Listeria monocytogenes
      infections in mice by intranasal and intravenous routes.
AB  - There have been no studies on the susceptibility and host immune responses to an
      intranasal infection with Listeria monocytogenes. In this study, we compared the
      susceptibilities and cytokine responses between intranasal and intravenous
      infections with L. monocytogenes in mice. Moreover, we compared efficiency of
      acquisition of host resistance to L. monocytogenes infection between intranasally
      and intravenously immunized mice because an intranasal immunization of vaccines
      is reportedly available for induction of adaptive immunity against various
      infectious pathogens. The susceptibility to an intranasal infection with L.
      monocytogenes was markedly lower than that to the intravenous infection. The
      bacterial growth in the lungs, spleens, and livers was substantially similar
      between intranasally and intravenously infected mice. Titers of endogenous gamma
      interferon (IFN-gamma) and tumor necrosis factor-alpha (TNF-alpha) in the
      spleens, livers, and lungs were parallel to bacterial numbers in each organ of
      mice during intranasal infection and intravenous infection. IFN-gamma-deficient
      mice and TNF-alpha-deficient mice were highly susceptible to intranasal infection
      as well as intravenous infection. Susceptibilities to intranasal and intravenous
      L. monocytogenes infection were the same in these cytokine-deficient mice. These
      results suggest that both IFN-gamma and TNF-alpha play critical roles in host
      resistance to intranasal L. monocytogenes infection as well as the intravenous
      infection. Acquisition of host resistance to intravenous and intranasal L.
      monocytogenes infection was induced in intranasally immunized mice as well as
      intravenously immunized mice, suggesting that intranasal immunization is
      effective for prevention of a systemic infection with L. monocytogenes.

PMID- 12183524
TI  - Immunization with the Chlamydia trachomatis mouse pneumonitis major outer
      membrane protein by use of CpG oligodeoxynucleotides as an adjuvant induces a
      protective immune response against an intranasal chlamydial challenge.
AB  - Recently, we have shown that a vaccine consisting of a purified preparation of
      the Chlamydia trachomatis mouse pneumonitis (MoPn) major outer membrane protein
      (MOMP) and Freund's adjuvant can protect mice against a genital challenge. Here,
      we wanted to determine if CpG motifs could be used as an immune modulator to the
      MOMP to induce protection in mice against an intranasal (i.n.) challenge. One
      week-old BALB/c mice were immunized intramuscularly and subcutaneously either
      once or three times at 2-week intervals with MOMP and CpG suspended in aluminum
      hydroxide (alum). Negative controls received ovalbumin, CpG, and alum. Positive
      controls were immunized i.n. with C. trachomatis MoPn elementary bodies (EB). Six
      weeks after the last immunization, mice were challenged i.n. with 10(4) inclusion
      forming units (IFU) of the C. trachomatis MoPn serovar. Mice that received MOMP,
      CpG, and alum had a strong immune response, as shown by a high titer of serum
      antibodies to Chlamydia and significant lymphoproliferation of T-cells following
      stimulation with C. trachomatis EB. After the i.n. challenge mice immunized with
      MOMP, CpG, and alum showed significantly less body weight loss than the
      corresponding control mice immunized with ovalbumin, CpG, and alum. Ten days
      after the challenge the animals were euthanized, their lungs were weighed, and
      the numbers of IFU in the lungs were determined. The average weight of the lungs
      of the mice immunized with MOMP, CpG, and alum was significantly less than
      average weight of the lungs of the mice immunized with ovalbumin, CpG, and alum.
      Also, the average number of IFU recovered per mouse immunized with MOMP, CpG, and
      alum was significantly less than the average number of IFU per mouse detected in
      the mice inoculated with ovalbumin, CpG, and alum. In conclusion, our data show
      that CpG sequences can be used as an effective adjuvant with the C. trachomatis
      MoPn MOMP to elicit a protective immune response in mice against a chlamydial
      respiratory challenge.

PMID- 12183525
TI  - Macrophage plasma membrane cholesterol contributes to Brucella abortus infection
      of mice.
AB  - Brucella abortus is a facultative intracellular bacterium capable of surviving
      inside macrophages. Intracellular replication of B. abortus requires the VirB
      complex, which is highly similar to conjugative DNA transfer systems. In this
      study, we show that plasma membrane cholesterol of macrophages is required for
      the VirB-dependent internalization of B. abortus and also contributes to the
      establishment of bacterial infection in mice. The internalization of B. abortus
      was accelerated by treating macrophages with acetylated low-density lipoprotein
      (acLDL). Treatment of acyl coenzyme A:cholesterol acyltransferase inhibitor, HL
      004, to macrophages preloaded with acLDL accelerated the internalization of B.
      abortus. Ketoconazole, which inhibits cholesterol transport from lysosomes to the
      cell surface, inhibited the internalization and intracellular replication of B.
      abortus in macrophages. The Niemann-Pick C1 gene (NPC1), the gene for Niemann
      Pick type C disease, characterized by an accumulation of cholesterol in most
      tissues, promoted B. abortus infection. NPC1-deficient mice were resistant to the
      bacterial infection. Molecules associated with cholesterol-rich microdomains,
      "lipid rafts," accumulate in intracellular vesicles of macrophages isolated from
      NPC1-deficient mice, and the macrophages yielded no intracellular replication of
      B. abortus. Thus, trafficking of cholesterol-associated microdomains controlled
      by NPC1 is critical for the establishment of B. abortus infection.

PMID- 12183526
TI  - virB-Mediated survival of Brucella abortus in mice and macrophages is independent
      of a functional inducible nitric oxide synthase or NADPH oxidase in macrophages.
AB  - The Brucella abortus virB locus is required for establishing chronic infection in
      the mouse. Using in vitro and in vivo models, we investigated whether virB is
      involved in evasion of the bactericidal activity of NADPH oxidase and the
      inducible nitric oxide synthase (iNOS) in macrophages. Elimination of NADPH
      oxidase or iNOS activity in macrophages in vitro increased recovery of wild-type
      B. abortus but not recovery of a virB mutant. In mice lacking either NADPH
      oxidase or iNOS, however, B. abortus infected and persisted to the same extent as
      it did in congenic C57BL/6 mice up until 60 days postinfection, suggesting that
      these host defense mechanisms are not critical for limiting bacterial growth in
      the mouse. A virB mutant did not exhibit increased survival in either of the
      knockout mouse strains, indicating that this locus does not contribute to evasion
      of nitrosative or oxidative killing mechanisms in vivo.

PMID- 12183527
TI  - Coadministration of an interleukin-12 gene and a Trypanosoma cruzi gene improves
      vaccine efficacy.
AB  - We tested the immunogenicity of two Trypanosoma cruzi antigens injected into mice
      in the form of DNA vaccine. Immunization with DNA encoding dihydroorotate
      dehydrogenase did not confer protective immunity in all mouse strains tested.
      Immunization with DNA encoding trans-sialidase surface antigen (TSSA) protected
      C57BL/6 (H-2(b)) mice but not BALB/c (H-2(d)) or C3H/Hej (H-2(k)) mice against
      lethal T. cruzi infection. In vivo depletion of CD4(+) or CD8(+) T cells
      abolished the protective immunity elicited by TSSA gene in C57BL/6 mice. Enzyme
      linked immunospot assay with splenocytes from T. cruzi-infected mice or TSSA gene
      vaccinated mice identified an H-2K(b)-restricted antigenic peptide, ANYNFTLV. The
      CD8(+)-T-cell line specific for this peptide could recognize T. cruzi-infected
      cells in vitro and could protect naive mice from lethal infection when adoptively
      transferred. Coadministration of the interleukin-12 (IL-12) gene with the TSSA
      gene facilitated the induction of ANYNFTLV-specific CD8(+) T cells and improved
      the vaccine efficacy against lethal T. cruzi infection. These results reinforced
      the utility of immunomodulatory adjuvants such as IL-12 gene for eliciting
      protective immunity against intracellular parasites by DNA vaccination.

PMID- 12183528
TI  - Induction of the gene encoding macrophage chemoattractant protein 1 by Orientia
      tsutsugamushi in human endothelial cells involves activation of transcription
      factor activator protein 1.
AB  - Human macrophage chemoattractant protein 1 (MCP-1) is a potent mediator of
      macrophage migration and therefore plays an essential role in early events of
      inflammation. In endothelial cells, at least three independent pathways regulate
      MCP-1 expression by NF-kappaB and AP-1. Orientia tsutsugamushi causes vasculitis
      in humans by replicating inside macrophages and endothelial cells. In the present
      study, we investigated the cis-acting and trans-acting elements involved in O.
      tsutsugamushi-induced MCP-1 gene expression in human umbilical vein endothelial
      cells (HUVEC). Although NF-kappaB activation was observed in HUVEC infected with
      O. tsutsugamushi, inhibition of NF-kappaB activation did not affect the MCP-1
      expression. However, treatment of HUVEC with extracellular signal-regulated
      kinase (ERK) kinase inhibitor or p38 mitogen-activated protein kinase (MAPK)
      inhibitor suppressed expression of MCP-1 mRNA concomitant with downregulation of
      activator protein 1 (AP-1) activation. Deletion of triphorbol acetate response
      elements (TRE) at position -69 to -63 of MCP-1 gene abolished inducible promoter
      activity. Deletion of TRE at position -69 to -63-96 to -90 or deletion of NF
      kappaB-binding site at position -69 to -63-88 to -79 did not affect the
      inducibility of promoter. Site-directed mutagenesis of the NF-kappaB binding
      sites at positions -2640 to -2632, -2612 to -2603 in the enhancer region, or the
      AP-1 biding site at position -2276 to -2270 decreased the inducible activity of
      the promoter. Taken together, AP-1 activation by both the ERK pathway and the p38
      MAPK pathway as well as their binding to TRE at position -69 to -63 in proximal
      promoter and TRE at position -2276 to -2270 in enhancer region is altogether
      essential in induction of MCP-1 mRNA in HUVEC infected with O. tsutsugamushi.
      Although NF-kappaB activation is not essential per se, the kappaB site in the
      enhancer region is important in MCP-1 induction of HUVEC. This discrepancy in the
      involvement of the NF-kappaB may be due to the function of chromatin structures
      and other transcription cofactors in the regulation of MCP-1 gene expression in
      response to O. tsutsugamushi infectioin.

PMID- 12183529
TI  - In vitro culture of Borrelia garinii results in loss of flagella and decreased
      invasiveness.
AB  - A virulent, low-passage culture of a tick-derived strain of Borrelia garinii was
      subjected to serial in vitro passages, from which inoculations were made into
      C3H/HeN mice. A full display of pathogenicity was observed through passage 4, as
      measured by cultures of ear punch biopsy samples and internal organs and
      determination of tibiotarsal joint swelling. Decreased dissemination through skin
      and infection of internal organs were observed beginning at passage 6. These
      losses correlated with both the selection of clones harboring 21% less flagella
      than the parent strain, as seen by electron microscopy, and loss of the motility
      of the higher passages, as demonstrated by a swarm assay. However, during the
      chronic phase (3 months after infection), spirochetes were cultured from the
      bladder and kidney of a mouse inoculated with passage 12. The kidney isolate had
      the same number of flagella and motility as the original low-passage isolate.
      Although we can't exclude the possibility that other subtle variations may be
      arising given the uncloned nature of the isolate, we have found a strong
      association between loss of flagella and decreased invasiveness. Arthritogenicity
      progressively decreased with passages, so that only 12.5% of chronically infected
      mice inoculated with passage 29 still presented with joint swelling, concurrent
      with a decrease in the staining intensity in a Southern blot with a vlsE-based
      probe. These results suggest a multifactorial model in which the number of
      flagella drives the invasiveness of this agent, while plasmid-associated factors
      are responsible for triggering arthritogenicity.

PMID- 12183530
TI  - Involvement of Lsp, a member of the LraI-lipoprotein family in Streptococcus
      pyogenes, in eukaryotic cell adhesion and internalization.
AB  - Three open reading frames (ORFs) were identified by a genome walking strategy in
      the genomes of serotype M49 group A streptococcal (GAS) strains CS101 and 591.
      These ORFs were located between the mga core regulon and the dipeptide permease
      operon. The deduced amino acid (aa) sequences contained signature sequences
      indicative of a lipoprotein (306 aa), an intracellular protein (823 aa), and a
      secreted peptide (66 aa), respectively. ORF1 (named Lsp for lipoprotein of
      Streptococcus pyogenes) and ORF2 exhibited a high degree of homology to the
      lmb/ORF2 genes of S. agalactiae (B. Spellerberg et al., Infect. Immun. 67:871
      878, 1999). The three ORFs were found to be present in each of the 27 GAS
      serotype strains tested. Transcription analysis revealed a polycistronic lsp/ORF2
      and a monocistronic ORF3 message that were detected primarily at the transition
      from exponential to stationary growth phase. lsp and ORF2 mutants, ORF2- and ORF3
      luciferase reporter fusions, and antiserum against recombinant Lsp were produced
      to examine the biological role of these genes. Although high Zn(2+) and Cu(2+)
      ion concentrations decreased lsp operon expression, Lsp did not transport
      divalent cations as described for other LraI-type operons. The lsp mutant had
      reduced fibronectin binding. Although no direct binding of Lsp to fibronectin
      could be demonstrated, the lsp mutant showed decreased transcription of prtF2
      encoding the fibronectin-binding protein F2. Both the lsp and ORF2 mutants showed
      decreased laminin binding. Adherence to and internalization into A549 epithelial
      cells of both mutants was reduced without a detectable effect on eukaryotic cell
      viability. The transcription of a number of virulence factors was altered in the
      lsp mutants and ORF2 mutants. The changes in laminin binding and eukaryotic cell
      internalization could be explained by changes in transcription of speB (cysteine
      protease) and/or the global regulators mga, csrRS, and nra.

PMID- 12183531
TI  - Incorporation of N-acetylneuraminic acid into Haemophilus somnus
      lipooligosaccharide (LOS): enhancement of resistance to serum and reduction of
      LOS antibody binding.
AB  - Haemophilus somnus isolates from cases of thrombotic meningoencephalitis,
      pneumonia, and other disease sites are capable of undergoing a high rate of phase
      variation in the oligosaccharide component of their lipooligosaccharides (LOS).
      In contrast, the LOS of commensal strains isolated from the normal reproductive
      tract phase vary little or not at all. In addition, the LOS of H. somnus shares
      conserved epitopes with LOS from Neisseria gonorrhoeae, Haemophilus influenzae,
      and other species that can incorporate sialic acid into their LOS. We now report
      that growth of disease isolates of H. somnus with CMP-N-acetylneuraminic acid
      (CMP-NeuAc) or NeuAc added to the medium resulted in incorporation of NeuAc into
      the LOS. However, NeuAc was not incorporated into the LOS of commensal isolates
      and one disease isolate following growth in medium containing CMP-NeuAc or NeuAc.
      Sialylated LOS was detected by an increase in the molecular size or an increase
      in the amount of the largest-molecular-size LOS electrophoretic bands, which
      disappeared following treatment with neuraminidase. Sialylated LOS could also be
      detected by reactivity with Limax flavus agglutinin lectin, which is specific for
      sialylated species, by dot blot assay; this reactivity was also reversed by
      neuraminidase treatment. H. somnus strain 2336 LOS was found to contain some
      sialic acid when grown in medium lacking CMP-NeuAc or NeuAc, although
      supplementation enhanced NeuAc incorporation. In contrast strain 738, an LOS
      phase variant of strain 2336, was less extensively sialylated when the growth
      medium was supplemented with CMP-NeuAc or NeuAc, as determined by electrophoretic
      profiles and electrospray mass spectrometry. The sialyltransferase of H. somnus
      strain 738 was confirmed to preferentially sialylate the Gal(beta)-(1-3)-GlcNAc
      component of the lacto-N-tetraose structure by capillary electrophoresis assay.
      Enhanced sialylation of the strain 2336 LOS inhibited the binding of monoclonal
      antibodies to LOS by enzyme immunoassay and Western blotting. Furthermore,
      sialylation of the LOS enhanced the resistance of H. somnus to the bactericidal
      action of antiserum to LOS. Sialylation and increased resistance to killing by
      normal serum also occurred in a deletion mutant that was deficient in the
      terminal Gal-GlcNAc disaccharide. LOS sialylation may therefore be an important
      virulence mechanism to protect H. somnus against the host immune system.

PMID- 12183532
TI  - The YadA protein of Yersinia pseudotuberculosis mediates high-efficiency uptake
      into human cells under environmental conditions in which invasin is repressed.
AB  - The YadA protein is a major adhesin of Yersinia pseudotuberculosis that promotes
      tight adhesion to mammalian cells by binding to extracellular matrix proteins. In
      this study, we first addressed the possibility of competitive interference of
      YadA and the major invasive factor invasin and found that expression of YadA in
      the presence of invasin affected neither the export nor the function of invasin
      in the outer membrane. Furthermore, expression of YadA promoted both bacterial
      adhesion and high-efficiency invasion entirely independently of invasin.
      Antibodies against fibronectin and beta(1) integrins blocked invasion, indicating
      that invasion occurs via extracellular-matrix-dependent bridging between YadA and
      the host cell beta(1) integrin receptors. Inhibitor studies also demonstrated
      that tyrosine and Ser/Thr kinases, as well as phosphatidylinositol 3-kinase, are
      involved in the uptake process. Further expression studies revealed that yadA is
      regulated in response to several environmental parameters, including temperature,
      ion and nutrient concentrations, and the bacterial growth phase. In complex
      medium, YadA production was generally repressed but could be induced by addition
      of Mg(2+). Maximal expression of yadA was obtained in exponential-phase cells
      grown in minimal medium at 37 degrees C, conditions under which the invasin gene
      is repressed. These results suggest that YadA of Y. pseudotuberculosis
      constitutes another independent high-level uptake pathway that might complement
      other cell entry mechanisms (e.g., invasin) at certain sites or stages during the
      infection process.

PMID- 12183533
TI  - Toll-like receptor 4 (TLR4)-deficient murine macrophage cell line as an in vitro
      assay system to show TLR4-independent signaling of Bacteroides fragilis
      lipopolysaccharide.
AB  - Bacterial lipopolysaccharides (LPS) activate cells of innate immunity, such as
      macrophages, by stimulating signaling through toll-like receptor 4 (TLR4). We and
      others have hypothesized that LPS derived from different bacterial species may
      function through TLR4-independent mechanisms. To test this hypothesis, we have
      generated using a nonviral transformation procedure a bone marrow-derived
      macrophage cell line called 10ScNCr/23 from mouse strain C57BL/10ScNCr. This
      mouse strain has a deletion of the TLR4 locus, causing the mouse strain to be
      nonresponsive to stimulation by LPS from Escherichia coli while responding
      normally to other bacterial substrates, such as lipoteichoic acid (LTA) from
      Staphylococcus aureus, which signal TLR4 independently. Stimulation with LTA
      induces five- and sixfold increases in 10ScNCr/23 cell line tumor necrosis factor
      alpha and macrophage inflammatory protein-2 (MIP-2) secretion, but no increases
      in either cytokine were found when cells were stimulated with E. coli LPS.
      Bacteroides fragilis-derived LPS, however, can effectively stimulate MIP-2
      expression in the absence of functional TLR4 in the 10ScNCr/23 cell line. This
      gives rise to the notion that LPS from some bacterial species will utilize
      alternative receptors to stimulate the innate immune response.

PMID- 12183534
TI  - Protection from group B streptococcal infection in neonatal mice by maternal
      immunization with recombinant Sip protein.
AB  - The protective potential of antibodies directed against group B streptococcus
      (GBS) Sip surface protein was determined by using the mouse neonatal infection
      model. Rabbit Sip-specific antibodies administered passively to pregnant mice
      protected their pups against a GBS lethal challenge. In addition, active
      immunization with purified recombinant Sip protein of female CD-1 mice induced
      the production of specific antibodies that also confer protection to the newborn
      pups against GBS strains of serotypes Ia/c, Ib, II, III, and V. These data
      confirm that Sip-specific antibodies can cross the placenta and conferred
      protective immunity against GBS infections.

PMID- 12183535
TI  - The Haemophilus influenzae Hap autotransporter binds to fibronectin, laminin, and
      collagen IV.
AB  - Nontypeable Haemophilus influenzae (NTHI) initiates infection by colonizing the
      upper respiratory tract mucosa. NTHI disease frequently occurs in the context of
      respiratory tract inflammation, where organisms encounter damaged epithelium and
      exposed basement membrane. In this study, we examined interactions between the H.
      influenzae Hap adhesin and selected extracellular matrix proteins. Hap is an
      autotransporter protein that undergoes autoproteolytic cleavage, with release of
      the adhesive passenger domain, Hap(s), from the bacterial cell surface. We found
      that Hap promotes bacterial adherence to purified fibronectin, laminin, and
      collagen IV and that Hap-mediated adherence is enhanced by inhibition of
      autoproteolysis. Adherence is inhibited by pretreatment of bacteria with a
      polyclonal antiserum recognizing Hap(s). Purified Hap(s) binds with high affinity
      to fibronectin, laminin, and collagen IV but not to collagen II. Binding of
      Hap(s) to fibronectin involves interaction with the 45-kDa gelatin-binding domain
      but not the 30-kDa heparin-binding domain of fibronectin. Taken together, these
      observations suggest that interactions between Hap and extracellular matrix
      proteins may play an important role in NTHI colonization of the respiratory
      tract.

PMID- 12183536
TI  - Streptococcal inhibitor of complement inhibits two additional components of the
      mucosal innate immune system: secretory leukocyte proteinase inhibitor and
      lysozyme.
AB  - Streptococcal inhibitor of complement (SIC) is a 31-kDa extracellular protein of
      a few, very virulent, strains of Streptococcus pyogenes (particularly M1
      strains). It is secreted in large quantities (about 5 mg/liter) and inhibits
      complement lysis by blocking the membrane insertion site on C5b67. We describe
      investigations into the interaction of SIC with three further major components of
      the innate immune system found in airway surface liquid, namely, secretory
      leukocyte proteinase inhibitor (SLPI), lysozyme, and lactoferrin. Enzyme-linked
      immunosorbent assays showed that SIC binds to SLPI and to both human and hen egg
      lysozyme (HEL) but not to lactoferrin. Studies using (125)I-labeled proteins
      showed that SIC binds approximately two molecules of SLPI and four molecules of
      lysozyme. SLPI binding shows little temperature dependence and a small positive
      enthalpy, suggesting that the binding is largely hydrophobic. By contrast,
      lysozyme binding shows strong temperature dependence and a substantial negative
      enthalpy, suggesting that the binding is largely ionic. Lysozyme is precipitated
      from solution by SIC. Further studies examined the ability of SIC to block the
      biological activities of SLPI and lysozyme. An M1 strain of group A streptococci
      was killed by SLPI, and the antibacterial activity of this protein was inhibited
      by SIC. SIC did not inhibit the antiproteinase activity of SLPI, implying that
      there is specific inhibition of the antibacterial domain. The antibacterial and
      enzymatic activities of lysozyme were also inhibited by SIC. SIC is the first
      biological inhibitor of the antibacterial action of SLPI to be described and may
      prove to be an important tool for investigating this activity in vivo. Inhibition
      of the antibacterial actions of SLPI and lysozyme would be advantageous to S.
      pyogenes in establishing colonization on mucosal surfaces, and we propose that
      this is the principal function of SIC.

PMID- 12183537
TI  - Nucleotidase cascades are catalyzed by secreted proteins of the parasitic
      nematode Trichinella spiralis.
AB  - Extracellular nucleotides are signaling molecules whose receptor-mediated effects
      are involved in a variety of physiological responses in mammalian tissues. An
      overwhelming body of data indicate that inflammatory and other immune responses
      can be modulated by the availability and local concentrations of nucleotides via
      nucleotide receptor signaling, but this is only just beginning to be investigated
      in the context of infectious disease. Evidence is provided here that the
      parasitic nematode Trichinella spiralis can catalyze the conversion and thus
      modulate both the availability and concentration of extracellular nucleotides by
      means of the following secreted exoenzymes: apyrase, 5'-nucleotidase, and
      adenosine deaminase. These enzymes were characterized in terms of substrate
      specificity, kinetic behavior, pH, divalent cation preferences, and response to a
      series of compounds. The secreted 5'-nucleotidase was identified as a protein
      with an apparent molecular mass of 67 kDa after N-terminal amino acid sequencing
      of the purified protein. The presence of adenosine deaminase was confirmed in the
      secreted products by Western blotting with an antibody against a mammalian
      enzyme, as a protein with an apparent molecular mass of 38 kDa. These secreted
      proteins constitute an enzymatic cascade which catalyzes the degradation of
      extracellular nucleotides, with a potential physiological role in the regulation
      of purinergic signaling.

PMID- 12183538
TI  - Identification and functional mapping of the Mycoplasma fermentans P29 adhesin.
AB  - Initial adherence interactions between mycoplasmas and mammalian cells are
      important for host colonization and may contribute to subsequent pathogenic
      processes. Despite significant progress toward understanding the role of
      specialized, complex tip structures in the adherence of some mycoplasmas,
      particularly those that infect humans, less is known about adhesins through which
      other mycoplasmas of this host bind to diverse cell types, even though simpler
      surface components are likely to be involved. We show by flow cytometric analysis
      that a soluble recombinant fusion protein (FP29), representing the abundant P29
      surface lipoprotein of Mycoplasma fermentans, binds human HeLa cells and inhibits
      M. fermentans binding to these cells, in both a quantitative and a saturable
      manner, whereas analogous fusion proteins representing other mycoplasma surface
      proteins did not. Constructs representing nested N- or C-terminal truncations of
      FP29 allowed initial mapping of this specific adherence function to a central
      region of the P29 sequence containing a 36-amino-acid disulfide loop. A
      derivative of FP29 containing a mutation converting one participating Cys to Ser,
      precluding intrachain disulfide bond formation, retained full activity. Together
      these results suggest that the direct interaction of M. fermentans with a ligand
      on the HeLa cell surface involves a limited segment of the P29 surface
      lipoprotein and requires neither the disulfide bond nor the contribution of
      adjacent portions of the protein. Earlier results indicating phase-variable
      display of monoclonal antibody surface epitopes on P29, now recognized to be
      outside this ligand binding region, raise the possibility that variation of
      mycoplasma surface architecture might alter the presentation of the binding
      region and the adherence phenotype. Preliminary results further indicated that
      FP29 could inhibit binding to HeLa cells by Mycoplasma hominis, a distinct human
      mycoplasma species displaying the phase-variable adhesin Vaa, but not that by
      Mycoplasma capricolum, an organism infecting caprine species. This result raises
      the additional, testable possibility that a common host cell ligand for two human
      mycoplasma species may be recognized through structurally dissimilar adhesins
      that undergo phase variation by two distinct mechanisms, governing protein
      expression (Vaa) or surface masking (P29).

PMID- 12183539
TI  - Characterization of the leptospiral outer membrane and description of three novel
      leptospiral membrane proteins.
AB  - The outer membrane (OM) of the mammalian pathogen Leptospira kirschneri was
      isolated in the form of membrane vesicles by alkaline plasmolysis and separated
      from the protoplasmic cylinder by sucrose density gradient ultracentrifugation.
      All four components of the alkaline plasmolysis buffer, including 1.0 M NaCl, 27%
      sucrose (wt/vol), 2 mM EDTA, and 10 mM Tris (pH 9), were required for efficient
      OM release, as judged by recovery of leptospiral lipopolysaccharide. Two
      populations of OM vesicles (OMVs) were recovered, with peak concentrations found
      in the sucrose gradient at densities of 1.16 and 1.18 g/ml. Transmission electron
      microscopy revealed that the more buoyant OMV population was smaller (<0.1 micro
      m in diameter) than the denser OMV population (0.2 to 0.3 micro m in diameter).
      The densities of both populations of OMVs were distinct from that of the
      protoplasmic-cylinder material, which was found in the sucrose gradient at a
      density of 1.20 g/ml. The OMV fractions were free of protoplasmic-cylinder
      material, as judged by immunoblotting with antibodies to the endoflagellar sheath
      protein, heat shock protein GroEL, and two novel cytoplasmic membrane proteins,
      lipoprotein LipL31 and transmembrane protein ImpL63. The protein components of
      the OMVs were characterized by one- and two-dimensional immunoblotting and found
      to include previously described OM proteins (OMPs), including the porin OmpL1;
      the lipoproteins LipL32, LipL36, and LipL41; and the peripheral membrane protein
      P31(LipL45). A number of less well-characterized OMPs were also identified,
      including those with molecular masses of 16, 21, 21.5, 22, 31, 36, 44, 48, 90,
      and 116 kDa. The 48-kDa OMP was identified as a novel OM lipoprotein designated
      LipL48. The use of membrane-specific markers in OM isolation techniques
      facilitates an accurate description of the leptospiral OM and its components.

PMID- 12183541
TI  - Effect of katG mutations on the virulence of Mycobacterium tuberculosis and the
      implication for transmission in humans.
AB  - The usefulness of isoniazid (INH), a key component of short-course chemotherapy
      of tuberculosis, is threatened by the emergence of drug-resistant strains of
      Mycobacterium tuberculosis with mutations in the katG gene. It is shown here that
      the most commonly occurring KatG mutation, where Ser 315 is replaced by Thr
      (S315T), is associated with clinically significant levels of INH resistance. In
      contrast to another resistant isolate, in which Pro replaces Thr 275, the S315T
      mutant produces active catalase-peroxidase and is virulent in the mouse model of
      the disease, indicating that a significant loss of bacterial fitness does not
      result from this frequent mutation. The implications of this finding for the
      transmission and reactivation of multidrug-resistant strains of M. tuberculosis
      are severe.

PMID- 12183540
TI  - Effect of vaccination with carrier protein on response to meningococcal C
      conjugate vaccines and value of different immunoassays as predictors of
      protection.
AB  - In order to plan for the wide-scale introduction of meningococcal C conjugate
      (MCC) vaccine for United Kingdom children up to 18 years old, phase II trials
      were undertaken to investigate whether there was any interaction between MCC
      vaccines conjugated to tetanus toxoid (TT) or a derivative of diphtheria toxin
      (CRM(197)) and diphtheria-tetanus vaccines given for boosting at school entry or
      leaving. Children (n = 1,766) received a diphtheria-tetanus booster either 1
      month before, 1 month after, or concurrently with one of three MCC vaccines
      conjugated to CRM(197) or TT. All of the MCC vaccines induced high antibody
      responses to the serogroup C polysaccharide that were indicative of protection.
      The immune response to the MCC-TT vaccine was reduced as a result of prior
      immunization with a tetanus-containing vaccine, but antibody levels were still
      well above the lower threshold for protection. Prior or simultaneous
      administration of a diphtheria-containing vaccine did not affect the response to
      MCC-CRM(197) vaccines. The immune responses to the carrier proteins were similar
      to those induced by a comparable dose of diphtheria or tetanus vaccine. The
      results also demonstrate that, for these conjugate vaccines in these age groups,
      both standard enzyme-linked immunosorbent assays and those that measure high
      avidity antibodies to meningococcal C polysaccharide correlated equally well with
      assays that measure serum bactericidal antibodies, the established serological
      correlate of protection for MCC vaccines.

PMID- 12183542
TI  - Control of mycobacterial replication in human macrophages: roles of extracellular
      signal-regulated kinases 1 and 2 and p38 mitogen-activated protein kinase
      pathways.
AB  - Intracellular persistence of mycobacteria may result from an intricate balance
      between bacterial replication and signaling events leading to antimicrobial
      macrophage activities. Using human monocyte-derived macrophages, we investigated
      the relevance of mitogen-activated protein kinase activation for the growth
      control of Mycobacterium avium isolates differing in their abilities to multiply
      intracellularly. The highly replicative smooth transparent morphotype of M. avium
      strain 2151 induced significantly less p38 and extracellular signal-regulated
      kinases 1 and 2 (ERK1/2) phosphorylation than the smooth opaque morphotype of the
      same strain, which was gradually eliminated from macrophage cultures. Inhibition
      of the p38 pathway by highly specific inhibitors did not significantly affect
      mycobacterial replication within macrophages, regardless of the in vitro
      virulence of the M. avium strain. However, repression of the ERK1/2 pathway
      further enhanced intracellular growth of highly replicative M. avium strains,
      although it did not increase survival of the poorly replicating M. avium isolate.
      Inhibition of the ERK1/2 pathway resulted in decreased tumor necrosis alpha (TNF
      alpha) secretion irrespective of the virulence of the M. avium isolate used for
      infection, revealing that TNF-alpha could have been only partially responsible
      for the control of intracellular M. avium growth. In conclusion, ERK1/2- and TNF
      alpha-independent pathways are sufficient to limit intramacrophage growth of less
      virulent M. avium strains, but early ERK1/2 activation in infected macrophages is
      critically involved in controlling the growth of highly replicative M. avium
      strains.

PMID- 12183543
TI  - The regulator PerR is involved in oxidative stress response and iron homeostasis
      and is necessary for full virulence of Streptococcus pyogenes.
AB  - Ferric uptake regulator (Fur) and Fur-like proteins form an important family of
      transcriptional regulators in many bacterial species. In this work we have
      characterized a Fur-like protein, the peroxide regulator PerR, in an M1 serotype
      of Streptococcus pyogenes. To determine the role of PerR in S. pyogenes, we
      inactivated the gene by allelic replacement. PerR-deficient bacteria showed 48%
      reduction of (55)Fe incorporation from the culture medium. Transcriptional
      analysis revealed that mtsA, encoding a metal-binding protein of an ABC
      transporter in S. pyogenes, was transcribed at lower levels than were wild-type
      cells. Although total iron accumulation was reduced, the growth of the mutant
      strain was not significantly hampered. The mutant showed hyperresistance to
      hydrogen peroxide, and this response was induced in wild-type cells by growth in
      aerobiosis, suggesting that PerR acts as an oxidative stress-responsive
      repressor. PerR may also participate in the response to superoxide stress, as the
      perR mutant was more sensitive to the superoxide anion and had a reduced
      transcription of sodA, which encodes the sole superoxide dismutase of S.
      pyogenes. Complementation of the mutation with a functional perR gene restored
      (55)Fe incorporation, response to peroxide stress, and transcription of both mtsA
      and sodA to levels comparable to those of wild-type bacteria. Finally, the perR
      mutant was attenuated in virulence in a murine air sac model of infection (P <
      0.05). These results demonstrate that PerR is involved in the regulation of iron
      homeostasis and oxidative stress responses and that it contributes to the
      virulence of S. pyogenes.

PMID- 12183545
TI  - Virulent combinations of adhesin and toxin genes in natural populations of
      Staphylococcus aureus.
AB  - Most cases of severe Staphylococcus aureus disease cannot be explained by the
      action of a single virulence determinant, and it is likely that a number of
      factors act in combination during the infective process. This study examined the
      relationship between disease in humans and a large number of putative virulence
      determinants, both individually and in combination. S. aureus isolates (n = 334)
      from healthy blood donors and from patients with invasive disease were compared
      for variation in the presence of 33 putative virulence determinants. After
      adjusting for the effect of clonality, seven determinants (fnbA, cna, sdrE, sej,
      eta, hlg, and ica) were significantly more common in invasive isolates. All seven
      factors contributed independently to virulence. No single factor predominated as
      the major predictor of virulence, their effects appearing to be cumulative. No
      combinations of the seven genes were either more or less likely to cause disease
      than others with the same number of virulence-associated genes. There was
      evidence of considerable horizontal transfer of genes on a background of
      clonality. Our findings also suggested that allelic variants of a polymorphic
      locus can make different contributions to the disease process, further study of
      which is likely to expand our understanding of staphylococcal disease
      pathogenesis.

PMID- 12183544
TI  - Structure-function relationships for human antibodies to pneumococcal capsular
      polysaccharide from transgenic mice with human immunoglobulin Loci.
AB  - To investigate the influence of antibody structure and specificity on antibody
      efficacy against Streptococcus pneumoniae, human monospecific antibodies (MAbs)
      to serotype 3 pneumococcal capsular polysaccharide (PPS-3) were generated from
      transgenic mice reconstituted with human immunoglobulin loci (XenoMouse mice)
      vaccinated with a PPS-3-tetanus toxoid conjugate and their molecular genetic
      structures, epitope specificities, and protective efficacies in normal and
      complement-deficient mice were determined. Nucleic acid sequence analysis of
      three MAbs (A7, 1A2, and 7C5) revealed that they use two different V(H)3 genes
      (A7 and 1A2 both use V3-15) and three different V(kappa) gene segments. The MAbs
      were found to have similar affinities for PPS-3 but different epitope
      specificities and CDR3 regions. Both A7 and 7C5 had a lysine at the V(H)-D
      junction, whereas 1A2 had a threonine. Challenge experiments with serotype 3 S.
      pneumoniae in BALB/c mice revealed that both 10- and 1- micro g doses of A7 and
      7C5 were protective, while only a 10- micro g dose of 1A2 was protective. Both A7
      and 7C5 were also protective in mice lacking either an intact alternative (FB(-/
      )) or classical (C4(-/-)) complement pathway, but 1A2 was not protective in
      either strain. Our data suggest that PPS-3 consists of epitopes that can elicit
      both highly protective and less protective antibodies and that the superior
      efficacies of certain antibodies may be a function of their structures and/or
      specificities. Further investigation of relationships between structure,
      specificity, and efficacy for defined MAbs to PPS may identify antibody features
      that might be useful surrogates for antibody (and vaccine) efficacy.

PMID- 12183546
TI  - Anthrax edema toxin requires influx of calcium for inducing cyclic AMP toxicity
      in target cells.
AB  - The anthrax edema toxin comprises two proteins: protective antigen and edema
      factor. Anthrax protective antigen binds to the receptors on the surface of
      target cells and facilitates the entry of edema factor into these target cells.
      Edema factor (EF) is an adenylate cyclase that catalyzes the synthesis of cyclic
      AMP (cAMP) in the cytosol of the host cells. In this study, we examined the
      requirement of extracellular calcium for anthrax edema toxin-induced toxicity in
      host cells. The cAMP response generated by edema toxin was analyzed in a variety
      of cells, including CHO, macrophage-like RAW264.7, human neutrophils, and human
      lymphocytes. Our investigations reveal that after EF reaches the cell cytosol, a
      rapid influx of calcium is triggered in the host cell that has a pivotal role in
      determining the cAMP response of the affected cells. Although the cAMP response
      generated by edema toxin in different cell types varied in intensity and in the
      time of initiation, the influx of calcium invariably preceded cAMP accumulation.
      Agents that blocked the uptake of calcium also inhibited edema toxin-induced
      accumulation of cAMP in the host cells. This is the first report that
      demonstrates that edema toxin induces accumulation of cAMP in lymphocytes. By
      accumulating cAMP, a potent inhibitor of immune cell function, edema toxin may
      actually be poisoning the immune system and thus facilitating the survival of the
      bacteria in the host.

PMID- 12183547
TI  - Tolerance to self gangliosides is the major factor restricting the antibody
      response to lipopolysaccharide core oligosaccharides in Campylobacter jejuni
      strains associated with Guillain-Barre syndrome.
AB  - Guillain-Barre syndrome following Campylobacter jejuni infection is frequently
      associated with anti-ganglioside autoantibodies mediated by molecular mimicry
      with ganglioside-like oligosaccharides on bacterial lipopolysaccharide (LPS). The
      regulation of antibody responses to these T-cell-independent antigens is poorly
      understood, and only a minority of Campylobacter-infected individuals develop
      anti-ganglioside antibodies. This study investigates the response to gangliosides
      and LPS in strains of mice by using a range of immunization strategies. In normal
      mice following intraperitoneal immunization, antibody responses to gangliosides
      and LPS are low level but can be enhanced by the antigen format or
      coadministration of protein to recruit T-cell help. Class switching from the
      predominant immunoglobulin M (IgM) response to IgG3 occurs at low levels,
      suggesting B1-cell involvement. Systemic immunization results in poor responses.
      In GalNAc transferase knockout mice that lack all complex gangliosides and
      instead express high levels of GM3 and GD3, generation of anti-ganglioside
      antibodies upon immunization with either complex gangliosides or ganglioside
      mimicking LPS is greatly enhanced and exhibits class switching to T-cell
      dependent IgG isotypes and immunological memory, indicating that tolerance to
      self gangliosides is a major regulatory factor. Responses to GD3 are suppressed
      in knockout mice compared with wild-type mice, in which responses to GD3 are
      induced specifically by GD3 and as a result of polyclonal B-cell activation by
      LPS. The anti-ganglioside response generated in response to LPS is also dependent
      on the epitope density of the ganglioside mimicked and can be further manipulated
      by providing secondary signals via lipid A and CD40 ligation.

PMID- 12183548
TI  - Pneumococcal infections in humans are associated with increased apoptosis and
      trafficking of type 1 cytokine-producing T cells.
AB  - Streptococcus pneumoniae infections are associated with considerable morbidity
      and mortality throughout the world. The immunopathology is characterized by an
      intense inflammatory reaction, including a strong acute-phase response and
      increased numbers of neutrophils in the circulation. However, little is known
      regarding the T-cell response during in vivo infections in humans. The purpose of
      this study was to test the hypothesis that activated T cells producing type 1
      cytokines were engaged in the host response to pneumococcal infections. The
      phenotype and function of T cells were studied in 22 patients at admission to a
      department of infectious diseases and after antibiotic treatment for 1 week
      compared with an age-matched, healthy control group. Pneumococcal infections
      induced lymphopenia in the circulation due to the disappearance of activated T
      lymphocytes with a type 1 cytokine profile. In contrast, the numbers of naive T
      cells and interleukin-4-producing T cells did not change. Activated type 1
      cytokine-producing cells reappeared in the circulation in relation to the
      treatment and clinical improvement. The underlying mechanisms during infection
      may include sequestration in the peripheral tissues and/or apoptosis. In fact,
      increased activation-induced apoptosis in the remaining peripheral lymphocytes
      and elevated levels of soluble Fas ligand were detected at admission to the
      hospital. In conclusion, these data suggest that activated T lymphocytes with a
      type 1 cytokine profile are highly engaged in the in vivo immune response to S.
      pneumoniae.

PMID- 12183549
TI  - Activation of p38 mitogen-activated protein kinase attenuates Leishmania donovani
      infection in macrophages.
AB  - Leishmania-induced macrophage dysfunctions have been correlated with altered
      signaling events. In this work, we report that SB203580, a specific inhibitor of
      p38 mitogen-activated protein kinases (MAPK), increases Leishmania donovani
      survival in human peripheral blood mononuclear macrophages. Consistent with this
      finding, activation of p38 and c-jun N-terminal kinase (JNK) MAPK signaling
      pathways by anisomycin significantly reduced parasite survival within these
      cells. However, the majority of the effect was seen in a 50% reduction in the
      percentage of macrophages infected, with little effect on the highly infected
      macrophages. The observed effect was likely to be due to the p38 MAPK pathway
      since SB203580 was able to completely reverse the effect of anisomycin. These
      findings suggest that the previously reported p38 MAPK inhibition by Leishmania
      infection may be partially overcome by anisomycin. Similar effects were observed
      in pretreated macrophages or in treatment of infected macrophages. These results
      suggests that p38 MAPK activation may have a potential therapeutic value in the
      treatment of visceral leishmaniasis.

PMID- 12183550
TI  - Identification and characterization of a Brucella abortus ATP-binding cassette
      transporter homolog to Rhizobium meliloti ExsA and its role in virulence and
      protection in mice.
AB  - Brucella abortus is a facultative intracellular bacterial pathogen that causes
      abortion in domestic animals and undulant fever in humans. The mechanism of
      virulence of Brucella spp. is not fully understood yet. Furthermore, genes that
      allow Brucella to reach the intracellular niche and to interact with host cells
      need to be identified. Using the genomic survey sequence (GSS) approach, we
      identified the gene encoding an ATP-binding cassette (ABC) transporter of B.
      abortus strain S2308. The deduced amino acid sequence encoded by this gene
      exhibited 69 and 67% identity with the sequences of the ABC transporters encoded
      by the exsA genes of Rhizobium meliloti and Mesorhizobium loti, respectively.
      Additionally, B. abortus ExsA, like R. meliloti and M. loti ExsA, possesses ATP
      binding motifs and the ABC signature domain features of a typical ABC
      transporter. Furthermore, ortholog group analysis placed B. abortus ExsA in
      ortholog group 6 of ABC transporters more likely to be involved in bacterial
      pathogenesis. In R. meliloti, ExsA is an exopolysaccharide transporter essential
      for alfalfa root nodule invasion and establishment of infection. To test the role
      of ExsA in Brucella pathogenesis, an exsA deletion mutant was constructed.
      Replacement of the wild-type exsA by recombination was demonstrated by Southern
      blot analysis of Brucella genomic DNA. Decreased survival in mice of the Brucella
      DeltaexsA mutant compared to the survival of parental strain S2308 demonstrated
      that ExsA is critical for full bacterial virulence. Additionally, the B. abortus
      exsA deletion mutant was used as a live vaccine. Challenge experiments revealed
      that the exsA mutant strain induced superior protective immunity in BALB/c mice
      compared to the protective immunity induced by strain S19 or RB51.

PMID- 12183551
TI  - Prevalence and boosting of antibodies to Plasmodium falciparum
      glycosylphosphatidylinositols and evaluation of their association with protection
      from mild and severe clinical malaria.
AB  - Glycosylphosphatidylinositols (GPIs), the anchor molecules of some membrane
      proteins of Plasmodium species, have been implicated in the induction of
      immunopathology during malaria infections. Hence, neutralization of GPIs by
      antibodies may reduce the severity of clinical attacks of malaria. To test this
      hypothesis, we have assessed the levels of anti-GPI antibodies in plasma from
      children and adults living in areas of seasonal malaria transmission in The
      Gambia. In a prospective study of susceptibility to clinical or asymptomatic
      infection, the levels of anti-GPI antibodies were measured before and after the
      transmission season. Samples were also obtained from children recruited into a
      hospital-based study of severe malaria. We find that in malaria-exposed
      individuals both the prevalence and the concentration of anti-GPI antibodies
      increase with age and that antibody levels are significantly higher at the end of
      the malaria transmission season than at the start of the season. Antibody levels
      are also higher in children with asymptomatic infections (i.e., those with a
      degree of clinical immunity) than in children who developed clinical malaria and
      high parasitemia, although this difference is not statistically significant.
      Importantly, antibodies appear to be rapidly boosted by clinical malaria
      infection, but children under the age of two years are seronegative for anti-GPI
      antibodies, even during an acute infection. While GPIs may be involved in the
      pathogenesis of human malaria, the data from this study do not provide any strong
      evidence to support the notion that anti-GPI antibodies confer resistance to mild
      or severe malarial disease. Further case-control studies, ideally of a
      prospective nature, are required to elucidate the role of antiglycolipid
      antibodies in protection from severe malaria.

PMID- 12183553
TI  - Bovine CD18 is necessary and sufficient to mediate Mannheimia (Pasteurella)
      haemolytica leukotoxin-induced cytolysis.
AB  - Leukotoxin (Lkt) secreted by Mannheimia (Pasteurella) haemolytica is an RTX toxin
      which is specific for ruminant leukocytes. Lkt binds to beta(2) integrins on the
      surface of bovine leukocytes. beta(2) integrins have a common beta subunit, CD18,
      that associates with three distinct alpha chains, CD11a, CD11b, and CD11c, to
      give rise to three different beta(2) integrins, CD11a/CD18 (LFA-1), CD11b/CD18
      (Mac-1), and CD11c/CD18 (CR4), respectively. Our earlier studies revealed that
      Lkt binds to all three beta(2) integrins, suggesting that the common beta
      subunit, CD18, may be the receptor for Lkt. In order to unequivocally elucidate
      the role of bovine CD18 as a receptor for Lkt, a murine cell line nonsusceptible
      to Lkt (P815) was transfected with cDNA for bovine CD18. One of the
      transfectants, 2B2, stably expressed bovine CD18 on the cell surface. The 2B2
      transfectant was effectively lysed by Lkt in a concentration-dependent manner,
      whereas the P815 parent cells were not. Immunoprecipitation of cell surface
      proteins of 2B2 with monoclonal antibodies specific for bovine CD18 or murine
      CD11a suggested that bovine CD18 was expressed on the cell surface of 2B2 as a
      heterodimer with murine CD11a. Expression of bovine CD18 and the Lkt-induced
      cytotoxicity of 2B2 cells were compared with those of bovine polymorphonuclear
      neutrophils and lymphocytes. There was a strong correlation between cell surface
      expression of bovine CD18 and percent cytotoxicity induced by Lkt. These results
      indicate that bovine CD18 is necessary and sufficient to mediate Lkt-induced
      cytolysis of target cells.

PMID- 12183552
TI  - Antibodies to Plasmodium falciparum glycosylphosphatidylinositols: inverse
      association with tolerance of parasitemia in Papua New Guinean children and
      adults.
AB  - Individuals living in regions of intense malaria transmission exhibit natural
      immunity that facilitates persistence of parasitemia at controlled densities for
      much of the time without symptoms. This aspect of immunity has been referred to
      as malarial "tolerance" and is thought to partly involve inhibition of the chain
      of events initiated by a parasite toxin(s) that may otherwise result in cytokine
      release and symptoms such as fever. Antibodies to the candidate Plasmodium
      falciparum glycosylphosphatidylinositol (GPI) toxin have been viewed as likely
      mediators of such tolerance. In this study, the relationship between antibodies
      to P. falciparum GPIs, age, and parasitemia was determined in asymptomatic
      children and adults living in Madang, Papua New Guinea. The prevalence and
      intensity of antibody responses increased with age and were lowest in children 1
      to 4 years old with the highest-density parasitemias. In children of this age
      group who were tolerant of parasitemia during the study, only 8.3% had detectable
      immunoglobulin G (IgG) and none had IgM antibodies to GPI. This suggests that
      anti-GPI antibodies are unlikely to be the sole mediator of malarial tolerance,
      especially in children younger than 5 years. Following antimalarial treatment,
      clearance of parasitemia led to a fall in anti-GPI IgG response in children and
      adolescents within 6 weeks. As anti-GPI antibodies potentially play a role in
      protecting against disease progression, our results caution against the treatment
      of asymptomatic parasitemia and suggest that generation of a sustained antibody
      response in children poses a challenge to novel antitoxic vaccination strategies.

PMID- 12183554
TI  - Cruzipain induces both mucosal and systemic protection against Trypanosoma cruzi
      in mice.
AB  - Cruzipain, the major cysteinyl proteinase of Trypanosoma cruzi, is expressed by
      all developmental forms and strains of the parasite and stimulates potent humoral
      and cellular immune responses during infection in both humans and mice. This
      information suggested that cruzipain could be used to develop an effective T.
      cruzi vaccine. To study whether cruzipain-specific T cells could inhibit T. cruzi
      intracellular replication, we generated cruzipain-reactive CD4(+) Th1 cell lines.
      These T cells produced large amounts of gamma interferon when cocultured with
      infected macrophages, resulting in NO production and decreased intracellular
      parasite replication. To study the protective effects in vivo of cruzipain
      specific Th1 responses against systemic T. cruzi challenges, we immunized mice
      with recombinant cruzipain plus interleukin 12 (IL-12) and a neutralizing anti-IL
      4 MAb. These immunized mice developed potent cruzipain-specific memory Th1 cell
      responses and were significantly protected against normally lethal systemic T.
      cruzi challenges. Although cruzipain-specific Th1 responses were associated with
      T. cruzi protective immunity in vitro and in vivo, adoptive transfer of cruzipain
      specific Th1 cells alone did not protect BALB/c histocompatible mice, indicating
      that additional immune mechanisms are important for cruzipain-specific immunity.
      To study whether cruzipain could induce mucosal immune responses relevant for
      vaccine development, we prepared recombinant attenuated Salmonella enterica
      serovar Typhimurium vaccines expressing cruzipain. BALB/c mice immunized with
      salmonella expressing cruzipain were significantly protected against T. cruzi
      mucosal infection. Overall, these data indicate that cruzipain is an important T.
      cruzi vaccine candidate and that protective T. cruzi vaccines will need to induce
      more than CD4(+) Th1 cells alone.

PMID- 12183555
TI  - Endogenous interleukin-12 is critical for controlling the late but not the early
      stage of Leishmania mexicana infection in C57BL/6 mice.
AB  - The role of interleukin-12 (IL-12) has been clearly established in the resistance
      of C57BL/6 (B6) mice to Leishmania major infection, but its involvement in the
      control of Leishmania mexicana infection remains to be determined. Here, we show
      the following. (i) L. mexicana, in contrast to L. major, induces the development
      of nonhealing lesions in B6 mice. (ii) Cells expressing IL-12p40, gamma
      interferon (IFN-gamma), NOS2, and CD40L are numerous in the footpad lesion and/or
      the draining popliteal lymph node of animals infected for up to 14 weeks with L.
      mexicana. (iii) B6 mice, either IL-12p40 deficient or treated with IL-12p40
      neutralizing antibodies, display a dramatic enhancement of primary and secondary
      lesions leading to death 10 weeks after inoculation with L. mexicana. (iv)
      Splenocytes harvested 4 and 8 weeks after infection of IL-12p40(-/-) B6 mice with
      L. mexicana are unable to produce IFN-gamma, but secrete IL-4, IL-10, and IL-18.
      Thus, the early control of L. mexicana infection by B6 mice is independent of IL
      12, whereas IL-12 and Th1 responses play a key role in controlling the late
      stages of L. mexicana infection. However, they fail to resolve lesions, in
      contrast to L. major infection, emphasizing the different outcomes induced by
      these two Leishmania species in B6 mice.

PMID- 12183556
TI  - Ganglioside mimicry of Campylobacter jejuni lipopolysaccharides determines
      antiganglioside specificity in rabbits.
AB  - The core oligosaccharides of Campylobacter jejuni lipopolysaccharides (LPS)
      display molecular mimicry with gangliosides. Cross-reactive anti-LPS
      antiganglioside antibodies have been implicated to show a crucial role in the
      pathogenesis of the Guillain-Barre and Miller Fisher syndrome. The specificity of
      the antiganglioside response is thought to depend on the oligosaccharide
      structure of the ganglioside mimic. To test this hypothesis and to investigate
      the potential of LPS from Campylobacter strains from enteritis patients to induce
      an antiganglioside response, we immunized rabbits with purified LPS from eight
      Campylobacter jejuni reference strains with biochemically well-defined distinct
      ganglioside mimics and determined the presence of antiganglioside antibodies. All
      rabbits produced immunoglobulin G (IgM) and IgG anti-LPS antibodies, and the
      specificity of the cross-reactive antiganglioside response indeed corresponded
      with the biochemically defined mimic. Most rabbits also had antibody reactivity
      against additional gangliosides, and there were slight differences in the fine
      specificity of the antibody response between rabbits that had been immunized with
      LPS from the same Campylobacter strain. High anti-LPS and antiganglioside titers
      persisted over a 10-month period. In conclusion, the structure of the LPS only
      partly determines the antiganglioside specificity. Other strain-specific as well
      as host-related factors influence the induction and fine-specificity of the cross
      reactive anti-LPS-antiganglioside response.

PMID- 12183557
TI  - Analysis of serum cross-reactivity and cross-protection elicited by immunization
      with DNA vaccines against Streptococcus pneumoniae expressing PspA fragments from
      different clades.
AB  - Streptococcus pneumoniae is a major cause of disease, especially in developing
      countries, and cost-effective alternatives to the currently licensed vaccines are
      needed. We constructed DNA vaccines based on pneumococcal surface protein A
      (PspA), an antigen shown to induce protection against pneumococcal bacteremia.
      PspA fragments can be divided into three families, which can be subdivided into
      six clades, on the basis of PspA amino acid sequence divergence (S. K.
      Hollingshead, R. Becker, and D. E. Briles, Infect. Immun. 68:5889-5900, 2000).
      Since most clinical isolates belong to family 1 or family 2, PspA fragments from
      members of both of these families were analyzed. Vectors encoding the complete N
      terminal regions of PspAs elicited significant humoral responses, and cross
      reactivity was mainly restricted to the same family. DNA vaccines encoding
      fusions between PspA fragments from family 1 and family 2 were also constructed
      and were able to broaden the cross-reactivity, with induction of antibodies that
      showed reactions with members of both families. At least for the pneumococcal
      strains tested, the cross-reactivity of antibodies was not reflected in cross
      protection. Animals immunized with DNA vaccines expressing the complete N
      terminal regions of PspA fragments were protected only against intraperitoneal
      challenge with a strain expressing PspA from the same clade.

PMID- 12183558
TI  - The human polymeric immunoglobulin receptor facilitates invasion of epithelial
      cells by Streptococcus pneumoniae in a strain-specific and cell type-specific
      manner.
AB  - Streptococcus pneumoniae is a gram-positive bacterial pathogen that causes
      invasive life-threatening disease worldwide. This organism also commonly
      colonizes the upper respiratory epithelium in an asymptomatic fashion. To invade,
      this pathogen must traverse the respiratory epithelial barrier, allowing it to
      cause disease locally or disseminate hematogenously throughout the body. Previous
      work has demonstrated that S. pneumoniae choline-binding protein A, a
      pneumococcal surface protein, interacts specifically with the human polymeric
      immunoglobulin receptor, which is expressed by cells in the respiratory
      epithelium. Choline-binding protein A is required for efficient colonization of
      the nasopharynx in vivo. Additionally, a recent study showed that the R6x
      laboratory strain of S. pneumoniae invades a human pharyngeal cell line in a
      human polymeric immunoglobulin receptor-dependent manner. These findings raised
      the possibility that the interaction between choline-binding protein A and human
      polymeric immunoglobulin receptor may be a key determinant of S. pneumoniae
      pathogenesis. However, the strain used in prior invasion studies, R6x, is an
      unencapsulated, nonpathogenic strain. In the present study we determined the
      relative ability of strain R6x or pathogenic strains to invade a variety of human
      polymeric immunoglobulin receptor-expressing epithelial cell lines. The results
      of this work suggest that human polymeric immunoglobulin receptor-dependent
      enhanced invasion of epithelial cells by S. pneumoniae is a limited phenomenon
      that occurs in a strain-specific and cell type-specific manner.

PMID- 12183559
TI  - Attenuated Salmonella enterica serovar Typhi expressing urease effectively
      immunizes mice against Helicobacter pylori challenge as part of a heterologous
      mucosal priming-parenteral boosting vaccination regimen.
AB  - Recombinant vaccine strains of Salmonella enterica serovar Typhi capable of
      expressing Helicobacter pylori urease were generated by transforming strains
      CVD908 and CVD908-htrA with a plasmid harboring the ureAB genes under the control
      of an in vivo-inducible promoter. The plasmid did not interfere with the ability
      of either strain to replicate and persist in human monocytic cells or with their
      transient colonization of mouse lungs. When administered to mice intranasally,
      both recombinant strains elicited antiurease immune responses skewed towards a
      Th1 phenotype. Vaccinated mice exhibited strong immunoglobulin G2a (IgG2a)-biased
      antiurease antibody responses as well as splenocyte populations capable of
      proliferation and gamma interferon (IFNgamma) secretion in response to urease
      stimulation. Boosting of mice with subcutaneous injection of urease plus alum
      enhanced immune responses and led them to a more balanced Th1/Th2 phenotype.
      Following parenteral boost, IgG1 and IgG2a antiurease antibody titers were raised
      significantly, and strong urease-specific splenocyte proliferative responses,
      accompanied by IFNgamma as well as interleukin-4 (IL-4), IL-5, and IL-10
      secretion, were detected. Neither immunization with urease-expressing S. enterica
      serovar Typhi alone nor immunization with urease plus alum alone conferred
      protection against challenge with a mouse-adapted strain of H. pylori; however, a
      vaccination protocol combining both immunization regimens was protective. This is
      the first report of effective vaccination against H. pylori with a combined
      mucosal prime-parenteral boost regimen in which serovar Typhi vaccine strains are
      used as antigen carriers. The significance of these findings with regard to
      development of a human vaccine against H. pylori and modulation of immune
      responses by heterologous prime-boost immunization regimens is discussed.

PMID- 12183560
TI  - Immunogenicity in a mouse model of a conjugate vaccine made with a synthetic
      single repeating unit of type 14 pneumococcal polysaccharide coupled to CRM197.
AB  - Oligosaccharides (OSs) related to the pneumococcal type 14 capsular
      polysaccharide (Pn14PS) were studied for their ability to inhibit the binding
      between anti-PS14 antisera and native PS14. A synthetic tetrasaccharide
      corresponding to the repeating unit of the Pn14PS, a hexasaccharide mimic, and an
      octasaccharide fragment obtained by Pn14PS depolymerization were good inhibitors.
      CRM197 conjugates of the tetrasaccharide and an octasaccharide mimic were
      prepared by using either adipic acid diester or diethyl squarate linkers. The
      conjugate with the tetrasaccharide chains induced anti-Pn14PS antibodies when
      injected subcutaneously into mice, as determined by an enzyme-linked
      immunosorbent assay, and antibody titers increased with oligosaccharide loading.
      The adipic acid-linked tetrasaccharide conjugates elicited higher antibody titers
      than those prepared with a squarate spacer. The lower anti-Pn14PS antibody
      response of the octasaccharide mimic conjugate indicates the importance of the
      backbone galactose residue for an appropriate antibody response. The OS-CRM197
      conjugate prepared from a single repeat unit of the Pn14PS is a potential vaccine
      candidate.

PMID- 12183561
TI  - Increased Trypanosoma cruzi invasion and heart fibrosis associated with high
      transforming growth factor beta levels in mice deficient in alpha(2)
      macroglobulin.
AB  - Trypanosoma cruzi proteinases are involved in host cell invasion in human
      patients and in mouse models. In mice, murine alpha(2)-macroglobulin (MAM) and
      murinoglobulin are circulating plasma proteinase inhibitors that also have
      important roles in inflammation and immune modulation. To define their role in
      experimental Chagas disease, we investigated the susceptibility to T. cruzi
      infection of mice that are deficient only in alpha2-macroglobulins (AM-KO) or in
      both MAM and monomeric murinoglobulin-1 (MM-KO), relative to the wild type (WT).
      Despite the high parasite load, parasitemia was lower in AM-KO and MM-KO mice
      than in WT mice. Nevertheless, we observed a significantly higher parasite load
      in the hearts of AM-KO and MM-KO mice, i.e., more amastigote nests and
      inflammatory infiltrates than in WT mice. This result demonstrates a protective
      role for MAM in the acute phase of murine T. cruzi infection. We further
      demonstrated in vitro that human alpha2-macroglobulins altered the trypomastigote
      morphology and motility in a dose-dependent way, and that also impaired T. cruzi
      invasion in cardiomyocytes. Finally, we demonstrated that the levels of
      transforming growth factor beta in AM-KO mice increased significantly in the
      third week postinfection, concomitant with high amastigote burden and important
      fibrosis. Combined, these in vivo and in vitro findings demonstrate that the MAM
      contribute to the resistance of mice to acute myocarditis induced by experimental
      T. cruzi infection.

PMID- 12183562
TI  - Histoplasma capsulatum synthesizes melanin-like pigments in vitro and during
      mammalian infection.
AB  - Melanin is made by several important pathogenic fungi and has been implicated in
      the pathogenesis of a number of fungal infections. This study investigated
      whether the thermally dimorphic fungal pathogen Histoplasma capsulatum var.
      capsulatum produced melanin or melanin-like compounds in vitro and during
      infection. Growth of H. capsulatum mycelia in chemically defined minimal medium
      produced pigmented conidia. Growth of H. capsulatum yeast in chemically defined
      minimal medium with L-3,4-dihydroxyphenylalanine (DOPA) or (-)-epinephrine
      produced pigmented cells. Treatment of the pigmented cells with proteolytic
      enzymes, denaturant, and hot concentrated acid yielded dark particles that were
      similar in size and shape to their respective propagules. Melanin-binding
      monoclonal antibodies (MAb) labeled pigmented conidia, yeast, and the isolated
      particles as determined by immunofluorescence microscopy. Electron spin resonance
      spectroscopy revealed that pigmented yeast cells and particles derived from
      pigmented cells were stable free radicals consistent with their identification as
      melanins. Tissues from mice infected with H. capsulatum and from biopsy specimens
      from a patient with histoplasmosis contained fungal cells that were labeled by
      melanin-binding MAb. Digestion of infected mouse tissues yielded dark particles
      that reacted with the melanin-binding MAb and were similar in appearance to H.
      capsulatum yeast cells. Additionally, sera from infected mice contained
      antibodies that bound melanin particles. Phenoloxidase activity capable of
      synthesizing melanin from L-DOPA was detected in cytoplasmic yeast cell extracts.
      These findings indicate that H. capsulatum conidia and yeast can produce melanin
      or melanin-like compounds in vitro and that yeast cells can synthesize pigment in
      vivo. Since melanin is an important virulence factor in other pathogenic fungi,
      this pigment may have a similar role to play in the pathogenesis of
      histoplasmosis.

PMID- 12183563
TI  - A Chlamydia trachomatis-specific Th2 clone does not provide protection against a
      genital infection and displays reduced trafficking to the infected genital
      mucosa.
AB  - A T helper type 1 (Th1) response is essential for resolving genital infections
      with the mouse pneumonitis biovar of Chlamydia trachomatis (MoPn). However, T
      cell-dependent anti-chlamydial antibody is produced and may also contribute to
      protective immunity. We produced a MoPn-specific CD4 Th2 clone (Th2-MoPn) to
      study the role of a Th2 response during infection. We found that Th2-MoPn was
      unable to eradicate chlamydiae from the genital tract (GT) when it was
      transferred into MoPn-infected nude mice. Mice that received Th2-MoPn produced
      greater titers of MoPn-specific serum immunoglobulin G (IgG) antibody than mice
      that received a MoPn-specific Th1 clone (Th1-MoPn) (log(10) titers, 1.89 +/- 0.84
      and 0.58 +/- 0.76 [mean +/- standard deviation], respectively [P < 0.01]). Also,
      the IgG isotypes were different for the two groups; whereas IgG1 was associated
      with Th2-MoPn, IgG2a was associated with Th1-MoPn. Also, infected nude mice that
      received Th2-MoPn produced higher levels of IgA in vaginal secretions. Although
      clone Th2-MoPn was detected in the GT, it was less efficient at migrating (112 +/
      35.6 labeled Th2 clone cells/10(5) GT cells) than Th1-MoPn (505 +/- 51.6 Th1
      clone cells/10(5) GT cells) (P < 0.001, as determined by a t test). This may have
      been due to reduced expression of alpha4beta7 and P-selectin ligand 1 on Th2
      MoPn. However, Th2-MoPn cells were retained in the GT during chronic infection
      and comprised 10 to 15% of the total GT cells 80 days after transfer. The data
      show that the MoPn-specific Th2 cells are important for serum and vaginal
      antibody production and may accumulate in the GT during chronic infection.

PMID- 12183564
TI  - Nitric oxide inhibits Coxiella burnetii replication and parasitophorous vacuole
      maturation.
AB  - Nitric oxide is a recognized cytotoxic effector against facultative and obligate
      intracellular bacteria. This study examined the effect of nitric oxide produced
      by inducible nitric oxide synthase (iNOS) up-regulated in response to cytokine
      stimulation, or by a synthetic nitric oxide donor, on replication of obligately
      intracellular Coxiella burnetii in murine L-929 cells. Immunoblotting and nitrite
      assays revealed that C. burnetii infection of L-929 cells augments expression of
      iNOS up-regulated in response to gamma interferon (IFN-gamma) and tumor necrosis
      factor alpha (TNF-alpha). Infection in the absence of cytokine stimulation did
      not result in demonstrable up-regulation of iNOS expression or in increased
      nitrite production. Nitrite production by cytokine-treated cells was
      significantly inhibited by the iNOS inhibitor S-methylisothiourea (SMT).
      Treatment of infected cells with IFN-gamma and TNF-alpha or the synthetic nitric
      oxide donor 2,2'-(hydroxynitrosohydrazino)bis-ethanamine (DETA/NONOate) had a
      bacteriostatic effect on C. burnetii replication. Inhibition of replication was
      reversed upon addition of SMT to the culture medium of cytokine-treated cells.
      Microscopic analysis of infected cells revealed that nitric oxide (either
      cytokine induced or donor derived) inhibited formation of the mature (large)
      parasitophorous vacuole that is characteristic of C. burnetii infection of host
      cells. Instead, exposure of infected cells to nitric oxide resulted in the
      formation of multiple small, acidic vacuoles usually containing one C. burnetii
      cell. Removal of nitrosative stress resulted in the coalescence of small vacuoles
      to form a large vacuole harboring multiple C. burnetii cells. These experiments
      demonstrate that nitric oxide reversibly inhibits replication of C. burnetii and
      formation of the parasitophorous vacuole.

PMID- 12183565
TI  - Effects of ageing on the immunoregulation of parasitic infection.
AB  - The plethora of changes associated with immunosenescence radically alters
      virtually all aspects of immune responsiveness. How this transformation effects
      resolution of an infectious challenge is addressed in this study. A well
      established infection model was used; Trichuris muris, a cecum-dwelling helminth,
      is natural to mice, and infection in different strains results in clearly
      polarized responses. A dominating T helper 2 (Th2) response orchestrates
      immunity, whereas a Th1 response will result in susceptibility. Mice between 19
      and 28 months old were more susceptible to infection, whereas 3-month-old mice of
      the same strain demonstrated the resistant phenotype. The cytokine response made
      by these aged mice was clearly altered at the site of infection, and within the
      local draining lymph nodes higher Th1 and lower Th2 cytokine levels were found,
      both at the protein and RNA level. Confirming these changes, aged mice also
      showed a delayed parasite-specific immunoglobulin G1 response and intestinal
      mastocytosis, both of which are driven by Th2 cytokines. To address possible
      causes of the observed immune deviation, purified CD4 cells from both young and
      aged mice were stimulated in vitro. Cells from aged mice did not respond to
      stimulation via CD28 and in vitro were less able to proliferate and polarize into
      Th2 cells; Th1 polarization was found to be normal. Together these data suggest
      that changes in cytokine phenotype, particularly CD4 cells, contribute to the
      observed age-associated switch from T. muris resistance to susceptibility.

PMID- 12183566
TI  - Efa1 influences colonization of the bovine intestine by shiga toxin-producing
      Escherichia coli serotypes O5 and O111.
AB  - Shiga toxin-producing Escherichia coli (STEC) comprises a broad group of
      bacteria, some of which cause attaching and effacing (AE) lesions and enteritis
      in animals and humans. Non-O157 STEC serotypes contain a gene (efa1) that
      mediates attachment to cultured epithelial cells. An almost-identical gene in
      enteropathogenic E. coli (lifA) encodes lymphostatin, which inhibits the
      proliferation of mitogen-activated lymphocytes and the synthesis of
      proinflammatory cytokines. We have investigated the role of the efa1 gene in
      colonization of 4- and 11-day-old conventional calves by STEC serotypes O5 and
      O111. Our findings show that Efa1 is required for efficient colonization of the
      bovine intestinal tract by STEC, since efa1 deletion and insertion mutants were
      shed in the feces in significantly lower numbers. In addition, efa1 mutations
      dramatically reduced the number of bacteria associated with the intestinal
      epithelium. Expression and secretion of locus for enterocyte effacement-encoded
      type III secreted proteins that are required for adhesion and AE-lesion formation
      were impaired by mutation of efa1 in STEC but not by mutation of lifA in
      enteropathogenic E. coli. However, STEC efa1 mutants retain the ability to
      nucleate filamentous actin under sites of bacterial attachment to cultured
      eukaryotic cells. Efa1 is only the second STEC factor shown to influence carriage
      of the bacteria in the bovine intestine. Our data may have implications for
      strategies to reduce the prevalence of STEC in cattle.

PMID- 12183567
TI  - Mycobacterium leprae infection in monocyte-derived dendritic cells and its
      influence on antigen-presenting function.
AB  - Host defense against Mycobacterium leprae infection is chiefly mediated by gamma
      interferon (IFN-gamma)-secreting cytotoxic T cells. Since which antigen
      presenting cell populations act to stimulate these T cells is not fully
      understood, we addressed the role of monocyte-derived dendritic cells (DCs). The
      DCs phagocytosed M. leprae and expressed bacterially derived antigens (Ags), such
      as phenolic glycolipid 1 (PGL-1), in the cytoplasm, as well as on the cell
      surface. The expression of HLA-ABC and -DR Ags on DCs was down-regulated by M.
      leprae infection, and that of CD86 was up-regulated, but not as fully as by
      Mycobacterium bovis BCG infection. Induction of CD83 expression required a large
      number of M. leprae cells. When a multiplicity of infection of >40 was used, the
      DCs induced a significant proliferative and IFN-gamma-producing response in
      autologous T cells. However, these responses were significantly lower than those
      induced by BCG- or Mycobacterium avium-infected DCs. A CD40-mediated signaling in
      M. leprae-infected DCs up-regulated the expression of HLA Ags, CD86, and CD83 but
      did not enhance T-cell-stimulating ability. Therefore, M. leprae-infected DCs are
      less efficient at inducing T-cell responses. However, when the surface PGL-1 on
      M. leprae-infected DCs was masked by a monoclonal antibody, the DCs induced
      enhanced responses in both CD4(+)- and CD8(+)-T-cell subsets. M. leprae is a
      unique pathogen which remains resistant to DC-mediated T-cell immunity, at least
      in the early stages of infection.

PMID- 12183568
TI  - Fcgamma receptor I- and III-mediated macrophage inflammatory protein 1alpha
      induction in primary human and murine microglia.
AB  - Microglial cell phagocytic receptors may play important roles in the pathogenesis
      and treatment of several neurological diseases. We studied microglial Fc receptor
      (FcR) activation with respect to the specific FcgammaR types involved and the
      downstream signaling events by using monoclonal antibody (MAb)-coated
      Cryptococcus neoformans immune complexes as the stimuli and macrophage
      inflammatory protein 1alpha (MIP-1alpha) production as the final outcome. C.
      neoformans complexed with murine immunoglobulin G (IgG) of gamma1, gamma2a, and
      gamma3, but not gamma2b isotype, was effective in inducing MIP-1alpha in human
      microglia. Since murine gamma2b binds to human FcgammaRII (but not FcgammaRI or
      FcgammaRIII), these results indicate that FcgammaRI and/or FcgammaRIII is
      involved in MIP-1alpha production. Consistent with this, an antibody that blocks
      FcgammaRII (IV.3) failed to inhibit MIP-1alpha production, while an antibody that
      blocks FcgammaRIII (3G8) did. An anti-C. neoformans MAb, 18B7 (IgG1), but not its
      F(ab')(2), induced extracellular signal-regulated kinase (ERK) mitogen-activated
      protein kinase kinase phosphorylation, and MIP-1alpha release was suppressed by
      the ERK inhibitor U0126. C. neoformans plus 18B7 also induced degradation of I
      kappaBalpha, and MIP-1alpha release was suppressed by the antioxidant NF-kappaB
      inhibitor pyrrolidine dithiocarbamate. To confirm the role of FcR more directly,
      we isolated microglia from wild-type and various FcR-deficient mice and then
      challenged them with C. neoformans plus 18B7. While FcgammaRII-deficient
      microglia showed little difference from the wild-type microglia, both FcgammaRI
      alpha-chain- and FcgammaRIII alpha-chain-deficient microglia produced less MIP
      1alpha, and the common Fc gamma-chain-deficient microglia showed no MIP-1alpha
      release. Taken together, our results demonstrate a definitive role for FcgammaRI
      and FcgammaRIII in microglial chemokine induction and implicate ERK and NF-kappaB
      as the signaling components leading to MIP-1alpha expression. Our results
      delineate a new mechanism for microglial activation and may have implications for
      central nervous system inflammatory diseases.

PMID- 12183569
TI  - The yeast Candida albicans binds complement regulators factor H and FHL-1.
AB  - The human facultative pathogenic yeast Candida albicans causes mucocutaneous
      infections and is the major cause of opportunistic fungal infections in
      immunocompromised patients. C. albicans activates both the alternative and
      classical pathway of the complement system. The aim of this study was to assay
      whether C. albicans binds human complement regulators in order to control
      complement activation at its surface. We observed binding of two central
      complement regulators, factor H and FHL-1, from normal human serum to C. albicans
      by adsorption assays, immunostaining, and fluorescence-activated cell sorter
      (FACS) analyses. Specificity of acquisition was further confirmed in direct
      binding assays with purified proteins. The surface-attached regulators maintained
      their complement regulatory activities and mediated factor I-dependent cleavage
      of C3b. Adsorption assays with recombinant deletion mutant proteins were used to
      identify binding domains. Two binding sites were localized. One binding domain
      common to both factor H and FHL-1 is located in the N-terminal short consensus
      repeat domains (SCRs) 6 and 7, and the other one located in C-terminal SCRs 19
      and 20 is unique to factor H. These data indicate that by surface acquisition of
      host complement regulators, the human pathogenic yeast C. albicans is able to
      regulate alternative complement activation at its surface and to inactivate toxic
      complement activation products.

PMID- 12183571
TI  - Hydrogen peroxide-mediated killing of Caenorhabditis elegans by Streptococcus
      pyogenes.
AB  - Caenorhabditis elegans is currently introduced as a new, facile, and cheap model
      organism to study the pathogenesis of gram-negative bacteria such as Pseudomonas
      aeruginosa and Salmonella enterica serovar Typhimurium. The mechanisms of killing
      involve either diffusible exotoxins or infection-like processes. Recently, it was
      shown that also some gram-positive bacteria kill C. elegans, although the precise
      mechanisms of killing remained open. We examined C. elegans as a pathogenesis
      model for the gram-positive bacterium Streptococcus pyogenes, a major human
      pathogen capable of causing a wide spectrum of diseases. We demonstrate that S.
      pyogenes kills C. elegans, both on solid and in liquid medium. Unlike P.
      aeruginosa and S. enterica serovar Typhimurium, the killing by S. pyogenes is
      solely mediated by hydrogen peroxide. Killing required live streptococci; the
      killing capacity depends on the amount of hydrogen peroxide produced, and killing
      can be inhibited by catalase. Major exotoxins of S. pyogenes are not involved in
      the killing process as confirmed by using specific toxin inhibitors and knockout
      mutants. Moreover, no accumulation of S. pyogenes in C. elegans is observed,
      which excludes the involvement of infection-like processes. Preliminary results
      show that S. pneumoniae can also kill C. elegans by hydrogen peroxide production.
      Hydrogen peroxide-mediated killing might represent a common mechanism by which
      gram-positive, catalase-negative pathogens kill C. elegans.

PMID- 12183570
TI  - Analysis of pathogen-host cell interactions in purpura fulminans: expression of
      capsule, type IV pili, and PorA by Neisseria meningitidis in vivo.
AB  - The pattern of meningococcal surface structure expression in different
      microenvironments following bloodstream invasion in vivo is not known. We used
      immunohistochemistry to determine the expression of capsule, type IV pili, and
      PorA by meningococci residing in the skin lesions of children with purpura
      fulminans. All the skin biopsy samples showed evidence of thrombosis and,
      frequently, a perivascular inflammatory cell infiltrate consisting of neutrophils
      (elastase positive) and monocytes/macrophages (CD68 positive). Modified Gram
      staining revealed 20 to over 100 gram-negative diplococci in each 4-microm-thick
      section, usually grouped into microcolonies. Immunoperoxidase staining
      demonstrated that the invading meningococci expressed PorA, capsule, and type IV
      pilin. Expression of these antigens was not restricted to any particular
      environment and was found in association with meningococci located in leukocytes,
      small blood vessels, and the dermal interstitium. Confocal laser scanning
      microscopy demonstrated coexpression of pilin and capsule by numerous
      microcolonies. However, there was some discordance in capsule and pilin
      expression within the microcolonies, suggesting phase variation. The strategy
      employed in this study will be helpful in investigating invasive bacterial
      diseases where antigenic and phase variation has a significant impact on
      virulence and on vaccine design.

PMID- 12183572
TI  - Increased host resistance against Pneumocystis carinii pneumonia in gammadelta T
      cell-deficient mice: protective role of gamma interferon and CD8(+) T cells.
AB  - Although a clear relationship between alphabeta T-cell receptor-positive
      (alphabeta-TCR(+)) CD4(+) T cells and susceptibility to Pneumocystis carinii
      infection exists, the role of other T-cell subsets is less clearly defined.
      Previous studies have shown that gammadelta-TCR(+) T cells infiltrate into the
      lung during P. carinii pneumonia. Therefore, the present study examined the role
      of gammadelta-TCR(+) T cells in host defense against P. carinii pneumonia.
      C57BL/6 (control) and B6.129P2-Tcrd(tm1Mom) (gammadelta-TCR(+) T-cell-deficient)
      mice were inoculated intratracheally with P. carinii. At specific time points,
      mice were sacrificed and analyzed for P. carinii burden, T-cell subsets, and
      cytokine levels in lung tissue. Analysis of P. carinii burden showed a more rapid
      and complete resolution of infection in gammadelta-TCR(+) T-cell-deficient mice
      than in C57BL/6 controls. This augmented resolution was associated with elevated
      gamma interferon (IFN-gamma) levels in bronchoalveolar lavage fluid predominantly
      produced by CD8(+) T cells, as well as an increased recruitment of CD8(+) T cells
      in general. In separate experiments, neutralization of IFN-gamma or depletion of
      CD8(+) T cells early during infection abolished the augmented resolution
      previously observed in gammadelta-TCR(+) T-cell-deficient mice. These results
      show that the presence of gammadelta-TCR(+) T cells modulates host susceptibility
      to P. carinii pneumonia through interactions with pulmonary CD8(+) T cells and
      tissue production of IFN-gamma.

PMID- 12183573
TI  - Mechanism of entry determines the ability of Toxoplasma gondii to inhibit
      macrophage proinflammatory cytokine production.
AB  - Macrophages (Mphi) infected with tachyzoites of the opportunistic protozoan
      Toxoplasma gondii are blocked in production of the proinflammatory cytokines
      tumor necrosis factor alpha (TNF-alpha) and interleukin-12 (IL-12) in response to
      lipopolysaccharide (LPS) triggering, and this is associated with parasite-induced
      inhibition of NFkappaB translocation. Here, we demonstrate a requirement for
      active invasion in the ability of the parasite to mediate suppression. Neither
      soluble tachyzoite antigen nor secreted products were suppressive, and heat
      inactivated, antibody-coated tachyzoites, which efficiently entered the cell
      through receptor-mediated uptake, failed to inhibit LPS responses. Cytochalasin
      D, a drug blocking tachyzoite invasion of, but not adherence to, Mphi, severely
      curtailed Toxoplasma-induced suppression. In addition, parasite-induced
      nonresponsiveness, as measured by TNF-alpha production, was reversed by treating
      infected cells with the toxoplasmastatic drugs pyrimethamine and 6-thioxanthine
      prior to LPS stimulation. A divergence in IL-12 and TNF-alpha responses was found
      during extended incubation of tachyzoites and Mphi in that 24 h of incubation of
      infected Mphi resulted in IL-12, but not TNF-alpha, secretion, and production of
      the latter cytokine remained suppressed when these cells were subjected to LPS
      triggering. Our results demonstrate that active invasion and survival of the
      parasite within the parasitophorous vacuole are required to induce and maintain
      Mphi cytokine-specific nonresponsiveness to LPS. They also show that the effects
      of Toxoplasma on IL-12 and TNF-alpha production are nonidentical, with the
      parasite exerting a longer-lasting suppression of the latter.

PMID- 12183574
TI  - Molecular genetic analyses of mating pheromones reveal intervariety mating or
      hybridization in Cryptococcus neoformans.
AB  - The sexual mating of the pathogenic yeast Cryptococcus neoformans is important
      for pathogenesis studies because the fungal virulence is linked to the alpha
      mating type (MAT(alpha)). We characterized C. neoformans mating pheromones
      (MF(alpha) 1 and MFa1) from 122 strains to understand intervariety hybridization
      or mating and intervariety virulence. MF(alpha) 1 in three C. neoformans
      varieties showed (a) specific nucleotide polymorphisms, (b) different copy
      numbers and chromosomal localizations, and (c) unique deduced amino acids in two
      geographic populations of C. neoformans var. gattii. MF(alpha) 1 of different
      varieties cross-hybridized in Southern hybridizations. Their phylogenetic
      analyses showed purifying selection (neutral evolution). These observations
      suggested that MAT(alpha) strains from any of the three C. neoformans varieties
      could mate or hybridize in nature with MATa strains of C. neoformans var.
      neoformans. A few serotype A/D diploid strains provided evidence for mating or
      hybridization, while a majority of A/D strains tested positive for haploid
      MF(alpha) 1 identical to that of C. neoformans var. grubii. MF(alpha) 1 sequence
      and copy numbers in diploids were identical to those of C. neoformans var.
      grubii, while their MFa1 sequences were identical to those of C. neoformans var.
      neoformans; thus, these strains were hybrids. The mice survival curves and
      histological lesions revealed A/D diploids to be highly pathogenic, with
      pathogenicity levels similar to that of the C. neoformans var. grubii type strain
      and unlike the low pathogenicity levels of C. neoformans var. neoformans strains.
      In contrast to MF(alpha) 1 in three varieties, MFa1 amplicons and hybridization
      signals could be obtained only from two C. neoformans var. neoformans reference
      strains and eight A/D diploids. This suggested that a yet undiscovered MFa
      pheromone(s) in C. neoformans var. gattii and C. neoformans var. grubii is
      unrelated to, highly divergent from, or rarer than that in C. neoformans var.
      neoformans. These observations could form the basis for future studies on the
      role of intervariety mating in C. neoformans biology and virulence.

PMID- 12183575
TI  - Identification and disruption of the gene encoding the third member of the low
      molecular-mass rhoptry complex in Plasmodium falciparum.
AB  - The low-molecular-mass rhoptry complex of Plasmodium falciparum consists of three
      proteins, rhoptry-associated protein 1 (RAP1), RAP2, and RAP3. The genes encoding
      RAP1 and RAP2 are known; however, the RAP3 gene has not been identified. In this
      study we identify the RAP3 gene from the P. falciparum genome database and show
      that this protein is part of the low-molecular-mass rhoptry complex. Disruption
      of RAP3 demonstrated that it is not essential for merozoite invasion, probably
      because RAP2 can complement the loss of RAP3. RAP3 has homology with RAP2, and
      the genes are encoded on chromosome 5 in a head-to-tail fashion. Analysis of the
      genome databases has identified homologous genes in all Plasmodium spp.,
      suggesting that this protein plays a role in merozoite invasion. The region
      surrounding the RAP3 homologue in the Plasmodium yoelii genome is syntenic with
      the same region in P. falciparum; however, there is a single gene. Phylogenetic
      comparison of the RAP2/3 protein family from Plasmodium spp. suggests that the
      RAP2/3 duplication occurred after divergence of these parasite species.

PMID- 12183576
TI  - The siderophore iron transporter of Candida albicans (Sit1p/Arn1p) mediates
      uptake of ferrichrome-type siderophores and is required for epithelial invasion.
AB  - The human fungal pathogen Candida albicans contains a close homologue of yeast
      siderophore transporters, designated Sit1p/Arn1p. We have characterized the
      function of SIT1 in C. albicans by constructing sit1 deletion strains and testing
      their virulence and ability to utilize a range of siderophores and other iron
      complexes. sit1 mutant strains are defective in the uptake of ferrichrome-type
      siderophores including ferricrocin, ferrichrysin, ferrirubin, coprogen, and
      triacetylfusarinine C. A mutation of FTR1 did not impair the use of these
      siderophores but did affect the uptake of ferrioxamines E and B, as well as of
      ferric citrate, indicating that their utilization was independent of Sit1p. Hemin
      was a source of iron for both sit1 and ftr1 mutants, suggesting a pathway of
      hemin uptake distinct from that of siderophores and iron salts. Heterologous
      expression of SIT1 in the yeast Saccharomyces cerevisiae confirmed the function
      of Sit1p as a transporter for ferrichrome-type siderophores. The sit1 mutant was
      defective in infection of a reconstituted human epithelium as a model for human
      oral mucosa, while the SIT1 strain was invasive. In contrast, both sit1 and SIT1
      strains were equally virulent in the mouse model of systemic infection. These
      results suggest that siderophore uptake by Sit1p/Arn1p is required in a specific
      process of C. albicans infection, namely epithelial invasion and penetration,
      while in the blood or within organs other sources of iron, including heme, may be
      used.

PMID- 12183577
TI  - Contribution of Candida albicans ALS1 to the pathogenesis of experimental
      oropharyngeal candidiasis.
AB  - We investigated the contribution of Candida albicans ALS1, which encodes a
      candidal adhesin, to the pathogenesis of experimental murine oropharyngeal
      candidiasis. Our results indicate that the ALS1 gene product is important for the
      adherence of the organism to the oral mucosa during the early stage of the
      infection.

PMID- 12183579
TI  - Simultaneous expression of different variant-specific surface proteins in single
      Giardia lamblia trophozoites during encystation.
AB  - A novel variant-specific surface protein (VSP) from Giardia was identified using
      the monoclonal antibody 9B10, raised against purified cyst walls. VSP9B10B is
      preferentially induced during encystation and expressed simultaneously with other
      VSPs on the surface of encysting trophozoites. These results support the
      hypothesis that encystation and antigenic variation are processes that are
      mechanistically related.

PMID- 12183578
TI  - Lipopolysaccharide desensitization of macrophages provides protection against
      Yersinia enterocolitica-induced apoptosis.
AB  - Pathogenic Yersinia spp. uncouple an array of signal transduction pathways in
      macrophages to disrupt their response to infection. This compels the macrophage
      to undergo apoptosis. Our study shows that macrophages that had acquired
      tolerance to Yersinia infection by preexposure to lipopolysaccharide were
      considerably protected against Y. enterocolitica-induced apoptosis. The
      desensitization of macrophages by lipopolysaccharide, which is thought to be a
      self-protective, adaptive response to sustained bacterial stimulation, may
      represent an immune mechanism that aids in overcoming Yersinia-mediated apoptosis
      and infection.

PMID- 12183580
TI  - Mixed periodontal Th1-Th2 cytokine profile in Actinobacillus
      actinomycetemcomitans-specific osteoprotegerin ligand (or RANK-L)- mediated
      alveolar bone destruction in vivo.
AB  - The Th1/Th2 cytokines involved in human periodontitis remain unclear; therefore,
      we established a humanized mouse model to investigate this issue in
      Actinobacillus actinomycetemcomitans-mediated periodontal infection. Quantitative
      PCR analysis clearly demonstrates a predominantly mixed Th1 and Th2 expression
      profile associated with pathogen-specific cell-mediated immunity via
      osteoprotegerin ligand (or RANK-L)-mediated alveolar bone destruction in vivo.

PMID- 12183581
TI  - Beta-1,2-mannosylation of Candida albicans mannoproteins and glycolipids differs
      with growth temperature and serotype.
AB  - Increasing the growth temperature from 28 to 37 degrees C reduced the expression
      of beta-1,2-oligomannoside epitopes on mannoproteins of Candida albicans
      serotypes A and B. In contrast, beta-1,2-mannosylation of phospholipomannan (PLM)
      remained constant despite a slight decrease in the relative molecular weight
      (M(r)) of this compound. At all growth temperatures investigated, serotype A PLM
      displayed an M(r) and an antigenicity different from those of serotype B PLM when
      they were tested with a panel of monoclonal antibodies.

PMID- 12183582
TI  - Functional domain of bovine milk lactoferrin which inhibits the adherence of
      Streptococcus mutans cells to a salivary film.
AB  - The bovine lactoferrin molecule and relatively long lactoferrin fragments
      containing residues 473 to 538 strongly inhibited adherence of Streptococcus
      mutans to saliva-coated hydroxyapatite beads. Each cysteine residue in Lf411
      (residues 473 to 538) was replaced by a serine residue, and the mutants Lf411
      C481S and Lf411-C532S strongly inhibited S. mutans adherence. These results
      suggest that the functional domain of lactoferrin that binds to a salivary film
      lies in residues 473 to 538 and that the region might be concealed by disulfide
      bond formation between Cys481 and Cys532 in the Lf411 fragment.

PMID- 12183583
TI  - A Dirofilaria immitis polyprotein up-regulates nitric oxide production.
AB  - We investigated the effect of recombinant Dirofilaria immitis polyprotein (rDiAg)
      on nitric oxide (NO) production by peritoneal macrophages. rDiAg induced NO
      production by macrophages from wild-type and lipopolysaccharide-hyporesponsive
      C3H/HeJ, but not CD40(-/-), mice. These results suggest that CD40 is involved in
      rDiAg-driven NO production by murine macrophages.

PMID- 12183584
TI  - Susceptibility of nontypeable Haemophilus influenzae to human beta-defensins is
      influenced by lipooligosaccharide acylation.
AB  - Nontypeable Haemophilus influenzae (NTHI) lipooligosaccharide htrB mutants
      exhibited greater than 45-fold-increased sensitivity to human beta-defensin 2
      (HBD-2) compared to the wild type. Complementation by htrB in trans to acylation
      competence reversed this increased sensitivity. In contrast, NTHI was more
      susceptible to HBD-3 and showed no changes in sensitivity as a result of
      lipooligosaccharide mutations in oligosaccharide and lipid A biosynthesis genes.

PMID- 12183585
TI  - A mutant of Burkholderia pseudomallei, auxotrophic in the branched chain amino
      acid biosynthetic pathway, is attenuated and protective in a murine model of
      melioidosis.
AB  - Using a transposon mutagenesis approach, we have identified a mutant of
      Burkholderia pseudomallei that is auxotrophic for branched chain amino acids. The
      transposon was shown to have interrupted the ilvI gene encoding the large subunit
      of the acetolactate synthase enzyme. Compared to the wild type, this mutant was
      significantly attenuated in a murine model of disease. Mice inoculated
      intraperitoneally with the auxotrophic mutant, 35 days prior to challenge, were
      protected against a challenge dose of 6,000 median lethal doses of wild-type B.
      pseudomallei.

PMID- 12183586
TI  - Differential expression of the p44 gene family in the agent of human granulocytic
      ehrlichiosis.
AB  - Using reverse transcription-PCR targeting of the p44 genes of the agent of human
      granulocytic ehrlichiosis (HGE) with primers flanking the hypervariable region,
      we show differential expression in a murine model of HGE infection and during
      tick transmission. The p44 genes were differentially expressed in salivary glands
      of infected nymphal ticks removed during transmission feeding but not in
      nonfeeding infected ticks. Similarly, the p44 genes were differentially expressed
      in infected C3H mice, in SCID mice, and in cultured HGE bacteria. Thus,
      differential p44 expression exists in vivo and in vitro and could provide a basis
      for antigenic variation.

PMID- 12183587
TI  - Campylobacter jejuni from patients with Guillain-Barre syndrome preferentially
      expresses a GD(1a)-like epitope.
AB  - GM(1)- and GD(1a)-like ganglioside mimicry in Campylobacter jejuni
      lipooligosaccharide (LOS) is considered to be involved in the pathogenesis of
      Campylobacter-induced Guillain-Barre syndrome (GBS). Compared with
      gastroenteritis-related isolates, GBS-related C. jejuni isolates were strongly
      associated with the expression of GD(1a)-like mimicry. The presence of a few
      genes involved in LOS ganglioside mimicry, cst-II, cgtA, and cgtB, was also
      associated with GBS-related strains. GD(1a)-like epitope expression may be an
      important virulence phenotype associated with the risk of developing GBS
      following campylobacter infection.

PMID- 12183588
TI  - Cellular immunity, but not gamma interferon, is essential for resolution of
      Babesia microti infection in BALB/c mice.
AB  - A new strain of Babesia microti (KR-1) was isolated from a Connecticut resident
      with babesiosis by hamster inoculation and adapted to C3H/HeJ and BALB/c mice. To
      examine the relative importance of humoral and cellular immunity for the control
      of B. microti infection, we compared the course of disease in wild-type BALB/c
      mice with that in BALB/c SCID mice, JHD-null (B-cell-deficient) mice, and T-cell
      receptor alphabeta (TCRbeta(-/-)) or gamma interferon (IFN-gamma) (IFN-gamma(-/
      )) knockout mice following inoculation with the KR-1-strain. SCID mice and
      TCRalphabeta knockouts sustained a severe but nonlethal parasitemia averaging 35
      to 45% infected erythrocytes. IFN-gamma-deficient mice developed a less severe
      parasitemia but were able to clear the infection. In contrast, in six of eight
      JHD-null mice, the levels of parasitemia were indistinguishable from those in the
      wild-type animals. These data indicate that cellular immunity is critical for the
      clearance of B. microti in BALB/c mice but that disease resolution can occur even
      in the absence of IFN-gamma.

PMID- 12183589
TI  - Borrelia burgdorferi erp (ospE-related) gene sequences remain stable during
      mammalian infection.
AB  - A number of studies have indicated that Borrelia burgdorferi erp genes need not
      vary during vertebrate infection. However, it was recently reported that a B.
      burgdorferi bacterium reisolated from an infected mouse evidenced mutation and
      recombination events in several erp genes. Reexamination of that reisolate
      indicates that the previously reported changes were no doubt artifacts of the PCR
      processes originally used to clone those DNAs. Thus, no evidence has been found
      of erp gene variation during mammalian infection.

PMID- 12183591
TI  - Shiga toxin 2 induces macrophage-granulocyte colonies from human bone marrow and
      cord blood stem cells.
AB  - Addition of Shiga toxin 2 to human bone marrow or cord blood cell culture induced
      macrophage-granulocyte colonies. Although Shiga toxin 2 alone induced colonies
      mainly composed of macrophages, it induced colonies mainly consisting of
      granulocytes when combined with physiological doses of interleukin-1beta,
      granulocyte colony-stimulating factor, or stem cell factor with interleukin-3.

PMID- 12183590
TI  - Salmonella enterica serovar Typhimurium periplasmic superoxide dismutases SodCI
      and SodCII are required for protection against the phagocyte oxidative burst.
AB  - Vitamin D(3) (1,25-dihydroxycholecalciferol) induced the phagocyte oxidative
      burst and intracellular killing of Salmonella enterica serovar Typhimurium in a
      phosphatidylinositol 3-kinase-dependent manner. The antimicrobial effect was more
      pronounced for Salmonella SodCI and SodCII mutants, confirming the role of the
      phagocyte oxidase in the vitamin D(3) effect. The results for an in vitro system
      with human THP-1 cells correlate with in vivo virulence data for mice and show
      that both the SodCI and SodCII enzymes are required to protect against the
      oxidative burst.

PMID- 12183592
TI  - Identification of genes affecting Salmonella enterica serovar enteritidis
      infection of chicken macrophages.
AB  - Screening of 7,680 Salmonella enterica serovar Enteritidis mutants for
      attenuation in a chicken macrophage infection model yielded a series of mutants
      including several with defects in previously unrecognized Salmonella virulence
      genes. One of the newly identified genes was the pbpA2 gene, belonging to the
      penicillin binding protein gene family.

PMID- 12183593
TI  - Neutrophil-mediated mycobacteriocidal immunity in the lung during Mycobacterium
      bovis BCG infection in C57BL/6 mice.
AB  - Although neutrophils have been identified as sources of inflammatory cytokines
      and chemokines, little is known about their immunologic function during
      mycobacterial infection in the lungs. In this study, we examined the growth of
      Mycobacterium bovis BCG in the lungs under experimental conditions that altered
      neutrophil recruitment to the lungs. Depletion and recruitment of neutrophils was
      associated with respective increases and decreases in M. bovis BCG growth. Thus,
      neutrophils may enhance mycobacteriocidal immunity in the lungs.

PMID- 12183594
TI  - The human immune response to Plasmodium falciparum includes both antibodies that
      inhibit merozoite surface protein 1 secondary processing and blocking antibodies.
AB  - Malaria merozoite surface protein 1 (MSP1) is cleaved in an essential step during
      erythrocyte invasion. The responses of children to natural malaria infection
      included antibodies that inhibit this cleavage and others that block the binding
      of these inhibitory antibodies. There was no correlation between the titer of the
      antibody to the 19-kDa fragment of MSP1 and its inhibitory activity. These
      findings have implications for the design of MSP1-based vaccines.

PMID- 12183595
TI  - Chlamydia pneumoniae and hyperlipidemia are co-risk factors for atherosclerosis:
      infection prior to induction of hyperlipidemia does not accelerate development of
      atherosclerotic lesions in C57BL/6J mice.
AB  - Chlamydia pneumoniae has been shown to accelerate atherosclerotic lesion
      development in hyperlipidemic animals. This study showed that C. pneumoniae did
      not accelerate lesion development in mice if a high-fat/high-cholesterol diet was
      started after infection, indicating that C. pneumoniae is a co-risk factor with
      hyperlipidemia for cardiovascular disease.

PMID- 12183596
TI  - Yersinia high-pathogenicity island contributes to virulence in Escherichia coli
      causing extraintestinal infections.
AB  - The Yersinia high-pathogenicity island (HPI) encodes an iron uptake system
      mediated by the siderophore yersiniabactin (Ybt) and confers the virulence of
      highly pathogenic Yersinia species. This HPI is also widely distributed in human
      pathogenic members of the family of Enterobacteriaceae, above all in
      extraintestinal pathogenic Escherichia coli (ExPEC). In the present study we
      demonstrate a highly significant correlation of a functional HPI and
      extraintestinal virulence in E. coli. Moreover, using a mouse infection model, we
      show for the first time that the HPI contributes to the virulence of ExPEC.

PMID- 12183597
TI  - The biosphere, health, and "sustainability".

PMID- 12183598
TI  - Evolution. Could poor nutrition have held life back?

PMID- 12183599
TI  - Language evolution. 'Speech gene' tied to modern humans.

PMID- 12183600
TI  - Number theory. Simple recipe creates acid test for primes.

PMID- 12183601
TI  - Italian reforms. Planned mergers raise hue and cry.

PMID- 12183602
TI  - Animal behavior. Birds spy on neighbors to choose nest sites.

PMID- 12183603
TI  - Computer security. Congress expands cyberfellows program.

PMID- 12183604
TI  - Patient records. Researchers welcome revised privacy rules.

PMID- 12183606
TI  - Biodefense. Peering into the shadows: Iraq's bioweapons program.

PMID- 12183605
TI  - Alternative medicine. NIH trial to test chelation therapy.

PMID- 12183607
TI  - Profile. Claudie Haignere: France's highflier comes down to earth.

PMID- 12183608
TI  - Astrophysics. Gravitational wave hunters take aim at the sky.

PMID- 12183609
TI  - Astrophysics. LIGO: the shakedown continues.

PMID- 12183610
TI  - Drug targeting. Breaking down barriers.

PMID- 12183611
TI  - Ecology. Conservation priorities for Russian mammals.

PMID- 12183612
TI  - Atmospheric chemistry. A marine source for alkyl nitrates.

PMID- 12183613
TI  - Biomedicine. Contact--how platelets touch von Willebrand factor.

PMID- 12183614
TI  - Genetic networks. Small numbers of big molecules.

PMID- 12183615
TI  - Physics. Resolving physical processes on the attosecond time scale.

PMID- 12183616
TI  - Neuroscience. It takes more than two to Nogo.

PMID- 12183617
TI  - Astronomy. The secrets behind supernovae.

PMID- 12183618
TI  - Development. Doublesex in the middle.

PMID- 12183619
TI  - Proterozoic ocean chemistry and evolution: a bioinorganic bridge?
AB  - Recent data imply that for much of the Proterozoic Eon (2500 to 543 million years
      ago), Earth's oceans were moderately oxic at the surface and sulfidic at depth.
      Under these conditions, biologically important trace metals would have been
      scarce in most marine environments, potentially restricting the nitrogen cycle,
      affecting primary productivity, and limiting the ecological distribution of
      eukaryotic algae. Oceanic redox conditions and their bioinorganic consequences
      may thus help to explain observed patterns of Proterozoic evolution.

PMID- 12183620
TI  - Allelic variation in human gene expression.

PMID- 12183621
TI  - Direct evidence for a marine source of C1 and C2 alkyl nitrates.
AB  - Alkyl nitrates are a significant component of the "odd nitrogen" reservoir and
      play an important role in regulating tropospheric ozone levels in remote marine
      regions. Measurements of methyl and ethyl nitrate in seawater and air samples
      along two Atlantic Ocean transects provide the first direct evidence for an
      oceanic source of these compounds. Equatorial surface waters were highly
      supersaturated (up to 800%) in both species, with the waters in the temperate
      regions generally being closer to equilibrium. A simple box model calculation
      suggests that the equatorial source could be a major component of the local
      atmospheric alkyl nitrate budget.

PMID- 12183622
TI  - Subduction and recycling of nitrogen along the Central American margin.
AB  - We report N and He isotopic and relative abundance characteristics of volatiles
      emitted from two segments of the Central American volcanic arc. In Guatemala,
      delta15N values are positive (i.e., greater than air) and N2/He ratios are high
      (up to 25,000). In contrast, Costa Rican N2/He ratios are low (maximum 1483) and
      delta15N values are negative (minimum -3.0 per mil). The results identify shallow
      hemipelagic sediments, subducted into the Guatemalan mantle, as the transport
      medium for the heavy N. Mass balance arguments indicate that the subducted N is
      efficiently cycled to the atmosphere by arc volcanism. Therefore, the subduction
      zone acts as a "barrier" to input of sedimentary N to the deeper mantle.

PMID- 12183624
TI  - Photothermal imaging of nanometer-sized metal particles among scatterers.
AB  - Ambient optical detection of labeled molecules is limited for fluorescent dyes by
      photobleaching and for semiconducting nanoparticles by "blinking" effects.
      Because nanometer-sized metal particles do not optically bleach, they may be
      useful optical labels if suitable detection signals can be found. We demonstrate
      far-field optical detection of gold colloids down to diameters of 2.5 nanometers
      with a photothermal method that combines high-frequency modulation and
      polarization interference contrast. The photothermal image is immune to the
      effects of scattering background, which limits particle imaging through Rayleigh
      scattering to diameters larger than 40 nanometers.

PMID- 12183623
TI  - Splay fault branching along the Nankai subduction zone.
AB  - Seismic reflection profiles reveal steeply landward-dipping splay faults in the
      rupture area of the magnitude (M) 8.1 Tonankai earthquake in the Nankai
      subduction zone. These splay faults branch upward from the plate-boundary
      interface (that is, the subduction zone) at a depth of approximately 10
      kilometers, approximately 50 to 55 kilometers landward of the trough axis,
      breaking through the upper crustal plate. Slip on the active splay fault may be
      an important mechanism that accommodates the elastic strain caused by relative
      plate motion.

PMID- 12183625
TI  - Electron solvation in two dimensions.
AB  - Ultrafast two-photon photoemission has been used to study electron solvation at
      two-dimensional metal/polar-adsorbate interfaces. The molecular motion that
      causes the excess electron solvation is manifested as a dynamic shift in the
      electronic energy. Although the initially excited electron is delocalized in the
      plane of the interface, interactions with the adsorbate can lead to its
      localization. A method for determining the spatial extent of the localized
      electron in the plane of the interface has been developed. This spatial extent
      was measured to be on the order of a single adsorbate molecule.

PMID- 12183626
TI  - Rotationally resolved infrared spectrum of the charge transfer complex [Ar-N2]+.
AB  - Difficulties in preparing cluster ions for spectroscopic studies have limited our
      understanding of intermolecular forces in charged complexes that are typical of
      many reactive intermediates. Here, the infrared spectrum of the charge transfer
      complex [Ar-N2]+, recorded in a supersonic planar plasma with a tunable diode
      laser spectrometer, is presented. More than 70 adjacent rovibrational transitions
      were measured near 2272 wave numbers and assigned to the molecular nitrogen
      stretching fundamental in the 2Sigma+ ground state of [Ar-N2]+. The accurate
      structural parameters that were determined confirm a linear structure and show
      that the major part of the charge is located at the argon atom. The latter result
      is surprising and implies a charge switch of the cationic center upon
      complexation.

PMID- 12183627
TI  - Public information and breeding habitat selection in a wild bird population.
AB  - According to the "public information" hypothesis, some animal species may monitor
      the current reproductive success of conspecifics to assess local habitat quality
      and to choose their own subsequent breeding site. To test this hypothesis
      experimentally, we manipulated two components of public information, the mean
      number of offspring raised locally ("quantity") and their condition ("quality"),
      in the collared flycatcher Ficedula albicollis. Immigration rate decreased with
      local offspring quantity but did not depend on local offspring quality,
      suggesting that immigrants are deprived of information regarding local quality.
      Conversely, emigration rate increased both when local offspring quantity or
      quality decreased, suggesting that residents can use both components of public
      information.

PMID- 12183628
TI  - Biosynthesis of the enediyne antitumor antibiotic C-1027.
AB  - C-1027 is a potent antitumor agent with a previously undescribed molecular
      architecture and mode of action. Cloning and characterization of the 85-kilobase
      C-1027 biosynthesis gene cluster from Streptomyces globisporus revealed (i) an
      iterative type I polyketide synthase that is distinct from any bacterial
      polyketide synthases known to date, (ii) a general polyketide pathway for the
      biosynthesis of both the 9- and 10-membered enediyne antibiotics, and (iii) a
      convergent biosynthetic strategy for the C-1027 chromophore from four building
      blocks. Manipulation of genes governing C-1027 biosynthesis allowed us to produce
      an enediyne compound in a predicted manner.

PMID- 12183629
TI  - The calicheamicin gene cluster and its iterative type I enediyne PKS.
AB  - The enediynes exemplify nature's ingenuity. We have cloned and characterized the
      biosynthetic locus coding for perhaps the most notorious member of the
      nonchromoprotein enediyne family, calicheamicin. This gene cluster contains an
      unusual polyketide synthase (PKS) that is demonstrated to be essential for
      enediyne biosynthesis. Comparison of the calicheamicin locus with the locus
      encoding the chromoprotein enediyne C-1027 reveals that the enediyne PKS is
      highly conserved among these distinct enediyne families. Contrary to previous
      hypotheses, this suggests that the chromoprotein and nonchromoprotein enediynes
      are generated by similar biosynthetic pathways.

PMID- 12183630
TI  - Structures of glycoprotein Ibalpha and its complex with von Willebrand factor A1
      domain.
AB  - Transient interactions of platelet-receptor glycoprotein Ibalpha (GpIbalpha) and
      the plasma protein von Willebrand factor (VWF) reduce platelet velocity at sites
      of vascular damage and play a role in haemostasis and thrombosis. Here we present
      structures of the GpIbalpha amino-terminal domain and its complex with the VWF
      domain A1. In the complex, GpIbalpha wraps around one side of A1, providing two
      contact areas bridged by an area of solvated charge interaction. The structures
      explain the effects of gain-of-function mutations related to bleeding disorders
      and provide a model for shear-induced activation. These detailed insights into
      the initial interactions in platelet adhesion are relevant to the development of
      antithrombotic drugs.

PMID- 12183631
TI  - Stochastic gene expression in a single cell.
AB  - Clonal populations of cells exhibit substantial phenotypic variation. Such
      heterogeneity can be essential for many biological processes and is conjectured
      to arise from stochasticity, or noise, in gene expression. We constructed strains
      of Escherichia coli that enable detection of noise and discrimination between the
      two mechanisms by which it is generated. Both stochasticity inherent in the
      biochemical process of gene expression (intrinsic noise) and fluctuations in
      other cellular components (extrinsic noise) contribute substantially to overall
      variation. Transcription rate, regulatory dynamics, and genetic factors control
      the amplitude of noise. These results establish a quantitative foundation for
      modeling noise in genetic networks and reveal how low intracellular copy numbers
      of molecules can fundamentally limit the precision of gene regulation.

PMID- 12183632
TI  - S-nitrosylation of matrix metalloproteinases: signaling pathway to neuronal cell
      death.
AB  - Matrix metalloproteinases (MMPs) are implicated in the pathogenesis of
      neurodegenerative diseases and stroke. However, the mechanism of MMP activation
      remains unclear. We report that MMP activation involves S-nitrosylation. During
      cerebral ischemia in vivo, MMP-9 colocalized with neuronal nitric oxide synthase.
      S-Nitrosylation activated MMP-9 in vitro and induced neuronal apoptosis. Mass
      spectrometry identified the active derivative of MMP-9, both in vitro and in
      vivo, as a stable sulfinic or sulfonic acid, whose formation was triggered by S
      nitrosylation. These findings suggest a potential extracellular proteolysis
      pathway to neuronal cell death in which S-nitrosylation activates MMPs, and
      further oxidation results in a stable posttranslational modification with
      pathological activity.

PMID- 12183634
TI  - Tech.Sight. Microfluidics. Microscale bioanalytical systems.

PMID- 12183633
TI  - Amphiphysin 2 (Bin1) and T-tubule biogenesis in muscle.
AB  - In striated muscle, the plasma membrane forms tubular invaginations (transverse
      tubules or T-tubules) that function in depolarization-contraction coupling.
      Caveolin-3 and amphiphysin were implicated in their biogenesis. Amphiphysin
      isoforms have a putative role in membrane deformation at endocytic sites. An
      isoform of amphiphysin 2 concentrated at T-tubules induced tubular plasma
      membrane invaginations when expressed in nonmuscle cells. This property required
      exon 10, a phosphoinositide-binding module. In developing myotubes, amphiphysin 2
      and caveolin-3 segregated in tubular and vesicular portions of the T-tubule
      system, respectively. These findings support a role of the bilayer-deforming
      properties of amphiphysin at T-tubules and, more generally, a physiological role
      of amphiphysin in membrane deformation.

PMID- 12183635
TI  - The role of sea spray in cleansing air pollution over ocean via cloud processes.
AB  - Particulate air pollution has been shown to strongly suppress precipitation from
      convective clouds over land. New observations show that precipitation from
      similar polluted clouds over oceans is much less affected, because large sea salt
      nuclei override the precipitation suppression effect of the large number of small
      pollution nuclei. Raindrops initiated by the sea salt grow by collecting small
      cloud droplets that form on the pollution particles, thereby cleansing the air.
      Therefore, sea salt helps cleanse the atmosphere of the air pollution via cloud
      processes. This implies that over oceans, the climatic aerosol indirect effects
      are significantly smaller than current estimates.

PMID- 12183636
TI  - Role of Rpn11 metalloprotease in deubiquitination and degradation by the 26S
      proteasome.
AB  - The 26S proteasome mediates degradation of ubiquitin-conjugated proteins.
      Although ubiquitin is recycled from proteasome substrates, the molecular basis of
      deubiquitination at the proteasome and its relation to substrate degradation
      remain unknown. The Rpn11 subunit of the proteasome lid subcomplex contains a
      highly conserved Jab1/MPN domain-associated metalloisopeptidase (JAMM) motif
      EX(n)HXHX(10)D. Mutation of the predicted active-site histidines to alanine
      (rpn11AXA) was lethal and stabilized ubiquitin pathway substrates in yeast.
      Rpn11(AXA) mutant proteasomes assembled normally but failed to either
      deubiquitinate or degrade ubiquitinated Sic1 in vitro. Our findings reveal an
      unexpected coupling between substrate deubiquitination and degradation and
      suggest a unifying rationale for the presence of the lid in eukaryotic
      proteasomes.

PMID- 12183637
TI  - Role of predicted metalloprotease motif of Jab1/Csn5 in cleavage of Nedd8 from
      Cul1.
AB  - COP9 signalosome (CSN) cleaves the ubiquitin-like protein Nedd8 from the Cul1
      subunit of SCF ubiquitin ligases. The Jab1/MPN domain metalloenzyme (JAMM) motif
      in the Jab1/Csn5 subunit was found to underlie CSN's Nedd8 isopeptidase activity.
      JAMM is found in proteins from archaea, bacteria, and eukaryotes, including the
      Rpn11 subunit of the 26S proteasome. Metal chelators and point mutations within
      JAMM abolished CSN-dependent cleavage of Nedd8 from Cul1, yet had little effect
      on CSN complex assembly. Optimal SCF activity in yeast and both viability and
      proper photoreceptor cell (R cell) development in Drosophila melanogaster
      required an intact Csn5 JAMM domain. We propose that JAMM isopeptidases play
      important roles in a variety of physiological pathways.

PMID- 12183638
TI  - Cellular mechanisms of neurogenic inflammation.
AB  - Since the initial observations that stimulation of sensory neurons produces
      vasodilation, plasma extravasation, and hypersensitivity, much progress has been
      made in understanding the etiology of neurogenic inflammation. Studies have
      focused largely on the role of the neuropeptides, substance P and calcitonin gene
      related peptide, which are released in the periphery by activation of small
      diameter sensory neurons. Recent work, however, has begun to emphasize the
      cellular mechanisms involved in regulating the release of proinflammatory
      substances from sensory neurons. In this perspective, discussion centers on a
      number of inflammatory mediators that activate various signal transduction
      pathways to augment excitability of and transmitter release from sensory neurons.
      Emphasis is placed on those pathways where multiple lines of evidence support
      their importance in initiating neurogenic inflammation. Recent studies, however,
      support the notion that there are novel compounds released during injury that can
      stimulate or sensitize sensory neurons. Furthermore, only now are intracellular
      signaling pathways that have been identified in other cell systems being studied
      in sensory neurons to establish their role in neurogenic inflammation. The
      challenge remains to ascertain the critical transduction pathways that regulate
      transmitter release from sensory neurons since this phenomenon triggers
      neurogenic inflammation. In addition, the cellular mechanisms involved in
      alterations in neuronal excitability during injury and the cellular pathways that
      maintain the inflammatory response over time need to be determined. With these
      advances, we will be able to develop therapeutic interventions to minimize
      deleterious consequences of neurogenic inflammation.

PMID- 12183639
TI  - Pharmacology of celecoxib in rat brain after kainate administration.
AB  - Prostaglandin E(2) (PGE(2)) is the major prostaglandin produced both centrally
      and in the periphery in models of acute and chronic inflammation, and its
      formation in both locations is blocked by cyclooxygenase-2 (COX-2) inhibitors
      such as celecoxib. In animal models of inflammation, PGE(2) inhibition in the
      brain may occur secondarily to a peripheral action by inhibiting local PG
      formation that elicits increased firing of pain fibers and consequent activation
      of PG synthesis in the central nervous system (CNS). Celecoxib was studied in the
      kainate-induced seizure model in the rat, a model of direct central prostaglandin
      induction, to determine whether it can act directly in the CNS. In the kainate
      treated rat brain there was increased PGE(2), PGF(2alpha), and PGD(2) production,
      with COX activity and PGE(2) formation increased about 7-fold over normal. We
      quantitated mRNA levels for enzymes involved in the prostaglandin biosynthetic
      pathways and found that both COX-2 and PGE synthase (PGEs) mRNA levels were
      increased in the brain; no changes were found for expression of COX-1 or PGD
      synthase mRNA. By Western blot analysis, COX-2 and PGEs were induced in total
      brain, hippocampus, and cortex, but not in the spinal cord. Immunohistological
      studies showed that COX-2 protein expression was enhanced in neurons.
      Dexamethasone treatment reduced the expression of both COX-2 and PGEs in kainate
      treated animals. Celecoxib reduced the elevated PGE(2) levels in brain of kainate
      treated rats and inhibited induced COX activity, demonstrating the ability of
      this compound to act on COX-2 in CNS. Doses of celecoxib that inhibited brain COX
      2 were lower than those needed for anti-inflammatory activity in adjuvant
      arthritis, demonstrating a potent direct central action of the compound.

PMID- 12183640
TI  - Paraherquamide and 2-deoxy-paraherquamide distinguish cholinergic receptor
      subtypes in Ascaris muscle.
AB  - Paraherquamide is a novel natural anthelmintic product with a mode of action that
      is incompletely characterized. Nicotine and cholinergic-anthelmintic agonists of
      different chemical classes were used to produce contraction in Ascaris muscle
      strips. Paraherquamide and a semisynthetic derivative, 2-deoxy-paraherquamide,
      antagonized these responses. Analysis of the actions of the antagonists was made
      using the simple competitive model and nonlinear regression to estimate the pK(B)
      values of the antagonists. The analysis was tested using Clark plots. The pK(B)
      values for paraherquamide were: nicotine, 5.86 +/- 0.14; levamisole, 6.61 +/-
      0.19; pyrantel, 6.50 +/- 0.11; and bephenium, 6.75 +/- 0.15. The pK(B) of
      nicotine was significantly different from the pK(B) values for levamisole,
      pyrantel, and bephenium, showing that paraherquamide can distinguish a subtype of
      cholinergic receptors sensitive to nicotine and a subtype of cholinergic
      receptors sensitive to levamisole, pyrantel, and bephenium. The pK(B) values for
      2-deoxy-paraherquamide were: levamisole, 5.31 +/- 0.13; pyrantel, 5.63 +/- 0.10;
      and bephenium, 6.07 +/- 0.13. The Clark plots of the antagonism illustrated the
      degree of fit to the competitive model for 2-deoxy-paraherquamide. 2-Deoxy
      paraherquamide selectively antagonized the effects of bephenium; the pK(B) values
      of levamisole and pyrantel were significantly different from the pK(B) of
      bephenium. Paraherquamide and 2-deoxy-paraherquamide are selective competitive
      cholinergic antagonists that distinguish subtypes of cholinergic receptor in
      Ascaris muscle corresponding to nicotine-, levamisole-, and bephenium-sensitive
      receptors.

PMID- 12183641
TI  - Polyethylene glycol reduces early and long-term cold ischemia-reperfusion and
      renal medulla injury.
AB  - Ischemia-reperfusion injury (IRI) after transplantation is a major cause of
      delayed graft function, which has a negative impact on early and late graft
      function and improve acute rejection. We have previously shown that polyethylene
      glycol (PEG) and particularly PEG 20M has a protective effect against cold
      ischemia and reperfusion injury in an isolated perfused pig and rat kidney model.
      We extended those observations to investigate the role of PEG using different
      doses (30g or 50g/l) added (ICPEG30 or ICPEG50) or not (IC) to a simplified
      preservation solution to reduce IRI after prolonged cold storage (48-h) of pig
      kidneys when compared with Euro-Collins and University of Wisconsin solutions.
      The study of renal function and medulla injury was performed with biochemical
      methods and proton NMR spectroscopy. Histological and inflammatory cell studies
      were performed after reperfusion (30-40 min) and on days 7 and 14 and weeks 4, 8,
      and 12. Peripheral-type benzodiazepine receptor (PBR), a mitochondrial protein
      involved in cholesterol homeostasis, was also studied. The results demonstrated
      that ICPEG30 improved renal function and reduced medulla injury. ICPEG30 also
      improved tubular function and strongly protect mitochondrial integrity. Post-IRI
      inflammation was strongly reduced in this group, particularly lymphocytes
      TCD4(+), PBR expression was influenced by IRI in the early period and during the
      development of chronic dysfunction. This study clearly shows that PEG has a
      beneficial effect in renal preservation and suggests a role of PBR as a marker
      IRI and repair processes.

PMID- 12183642
TI  - Pharmacology of INS37217 [P(1)-(uridine 5')-P(4)- (2'-deoxycytidine
      5')tetraphosphate, tetrasodium salt], a next-generation P2Y(2) receptor agonist
      for the treatment of cystic fibrosis.
AB  - INS37217 [P(1)-(uridine 5')-P(4)-(2'-deoxycytidine 5')tetraphosphate, tetrasodium
      salt] is a deoxycytidine-uridine dinucleotide with agonist activity at the P2Y(2)
      receptor. In primate lung tissues, the P2Y(2) receptor mRNA was located by in
      situ hybridization predominantly in epithelial cells and not in smooth muscle or
      stromal tissue. The pharmacologic profile of INS37217 parallels that of UTP,
      leading to increased chloride and water secretion, increased cilia beat
      frequency, and increased mucin release. The combined effect of these actions was
      confirmed in an animal model of tracheal mucus velocity that showed that a single
      administration of INS37217 significantly enhanced mucus transport for at least 8
      h after dosing. This extended duration of action is consistent with the ability
      of INS37217 to resist metabolism by airway cells and sputum enzymes. The enhanced
      metabolic stability and resultant increased duration of improved mucociliary
      clearance may confer significant advantages to INS37217 over other P2Y(2)
      agonists in the treatment of diseases such as cystic fibrosis.

PMID- 12183643
TI  - Protection and reversal of excitotoxic neuronal damage by glucagon-like peptide-1
      and exendin-4.
AB  - Glucagon-like peptide-1 (7-36)-amide (GLP-1) is an endogenous insulinotropic
      peptide that is secreted from the L cells of the gastrointestinal tract in
      response to food. It has potent effects on glucose-dependent insulin secretion,
      insulin gene expression, and pancreatic islet cell formation. In type 2 diabetes,
      GLP-1, by continuous infusion, can normalize blood glucose and is presently being
      tested in clinical trials as a therapy for this disease. More recently, GLP-1 has
      been found to have central nervous system (CNS) effects and to stimulate neurite
      outgrowth in cultured cells. We now report that GLP-1, and its longer-acting
      analog exendin-4, can completely protect cultured rat hippocampal neurons against
      glutamate-induced apoptosis. Extrapolating these effects to a well defined rodent
      model of neurodegeneration, GLP-1 and exendin-4 greatly reduced ibotenic acid
      induced depletion of choline acetyltransferase immunoreactivity in basal
      forebrain cholinergic neurons. These findings identify a novel
      neuroprotective/neurotrophic function of GLP-1 and suggest that such peptides may
      have potential for halting or reversing neurodegenerative processes in CNS
      disorders, such as Alzheimer's disease, and in neuropathies associated with type
      2 diabetes mellitus.

PMID- 12183644
TI  - Pharmacological properties of nicotinic acetylcholine receptors expressed by
      guinea pig small intestinal myenteric neurons.
AB  - The electrophysiological and pharmacological properties of nicotinic
      acetylcholine receptors (nAChRs) were studied in guinea pig small intestinal
      myenteric neurons maintained in culture or in acutely isolated preparations.
      Acetylcholine and nicotine caused inward currents that desensitized in
      approximately 4 s. The current-voltage (I-V) relationship rectified inwardly with
      a reversal potential near 0 mV. The agonist rank order potency was 1,1-dimethyl-4
      phenyl-piperazinium > acetylcholine = nicotine >> cytisine. Agonist-induced
      currents were blocked by nAChR antagonists with a rank order potency of
      mecamylamine > hexamethonium > dihydro-beta-erythroidine (DHbetaE); mecamylamine
      and DHbetaE exhibit high potency at beta4 and beta2 subunit-containing nAChRs,
      respectively. alpha-Bungarotoxin (0.1 microM) or alpha-methyllycaconitine (0.1
      microM), antagonists that block nAChRs containing alpha7 subunits, did not affect
      acetylcholine-induced responses. Immunohistochemical studies revealed that nearly
      every neuron in culture was labeled by an antibody (mAb35) that recognizes nAChR
      alpha3 and alpha5 subunits. Antibodies selective for alpha3, alpha5, or beta2
      subunits also stained most neurons, whereas an alpha7 subunit antibody revealed
      very few neurons. In neurons in the intact myenteric plexus from newborn and
      adult guinea pigs, local application of acetylcholine (1 mM) and cytisine (1 mM)
      caused similar amplitude depolarizations, and these responses were blocked by
      nAChR antagonists with a rank order potency of mecamylamine > hexamethonium >
      DHbetaE. These data indicate that myenteric neurons maintained in culture
      predominantly express nAChRs composed of alpha3, alpha5, beta2, and beta4
      subunits. These subunits may be in a homogeneous population of receptors with
      unique pharmacological properties, or multiple receptors of different subunit
      composition may be expressed by individual neurons.

PMID- 12183645
TI  - Changes in cardiovascular responsiveness and cardiotoxicity elicited during binge
      administration of Ecstasy.
AB  - The recreational use of 3,4-methylenedioxymethamphetamine (MDMA; Ecstasy) is
      often characterized by a repeated pattern of frequent drug administrations
      (binge) followed by a period of abstinence. Radiotelemetry was used to
      characterize the cardiovascular responses elicited during three MDMA binges (3 or
      9 mg/kg b.i.d. for 4 days), each of which was separated by a 10-day MDMA-free
      period. The heart rate and mean arterial pressure (MAP) responses elicited by 3
      mg/kg doses of MDMA were consistent within and between the three binges. In the
      first binge the 9-mg/kg doses of MDMA increased MAP and produced a biphasic
      (decrease/increase) heart rate response. The bradycardia elicited by MDMA in the
      first binge (-75 bpm) was enhanced in the second and third binges (-186 and -287
      bpm, respectively). Significant hypotension accompanied the increased bradycardic
      responses. Atropine abolished the hypotension and significantly attenuated the
      bradycardic responses. The MAP and heart rate responses elicited by sodium
      nitroprusside, acetylcholine, phenylephrine, and serotonin (5-HT) were evaluated
      before each binge and 10 days after the last binge. The hypotension, but not the
      tachycardia elicited by sodium nitroprusside was attenuated by the repeated
      administration of MDMA. The responses to phenylephrine, acetylcholine, and 5-HT
      were unaltered after MDMA. The hearts of treated rats contained foci of
      inflammatory infiltrates (lymphocytes and macrophages), some of which contained
      necrotic cells and/or disrupted cytoarchitecture. MDMA produced cardiac
      arrhythmias in some rats. These results indicate that the binge administration of
      MDMA can significantly alter cardiovascular and cardiovascular reflex function
      and produce cardiac toxicity.

PMID- 12183646
TI  - Amelioration of chronic and spontaneous intestinal inflammation with an antisense
      oligonucleotide (ISIS 9125) to intracellular adhesion molecule-1 in the HLA
      B27/beta2 microglobulin transgenic rat model.
AB  - Adhesion molecules are known to be an important part of leukocyte migration and
      extravasation in both homeostatic and inflammatory conditions. Intracellular
      adhesion molecule-1 (ICAM-1 or CD54) is constitutively expressed on endothelial
      cells and is up-regulated during acute and chronic inflammation. We investigated
      the efficacy and consequences of interfering with CD54 after administration of an
      antisense oligonucleotide to ICAM-1 (CD54) in the transgenic HLA-B27/beta2
      microglobulin rat model. One hundred percent of the HLA-B27 transgene + animals
      will spontaneously develop chronic inflammation (some more severely than others)
      in the gastric mucosa, cecum, and colon. We carried out two studies, i.p.
      injection and rectal administration of antisense. Following i.p. and rectal
      treatment, there were significant decreases in colonic mucosal wall thickness,
      histologic inflammation, CD54 expression in the colon and peripheral blood, and
      the percentage of colon weight per end body weight. Furthermore, decreased
      expression of CD49d, CD18, and tumor necrosis factor-alpha was observed in
      antisense treated rats. Therefore, the HLA-B27 transgenic model of spontaneous
      and chronic inflammatory bowel disease, which has increased expression of
      adhesion molecules, responds to both routes of administration of ICAM-1 antisense
      oligonucleotides. These studies support the regulatory role of adhesion molecules
      in chronic intestinal inflammation, the need for an understanding of how the
      route of drug delivery can alter the dose and area affected, and finally the role
      of antisense oligonucleotides as a therapeutic modality in chronic spontaneous
      inflammatory bowel diseases.

PMID- 12183647
TI  - Calcium-independent phospholipase A(2)-derived arachidonic acid is essential for
      endothelium-dependent relaxation by acetylcholine.
AB  - The role of calcium-independent phospholipase A(2) (iPLA(2))-produced arachidonic
      acid (AA) in acetylcholine (ACh)-mediated, endothelium-dependent vascular
      relaxation was investigated. ACh-induced relaxation of phenylephrine-constricted
      isolated rat mesenteric resistance arteries was attenuated following pretreatment
      with (E)-6-(bromomethylene)tetrahydro-3-(1-naphthalenyl)-2H-pyran-2-one (BEL; 1
      microM; p < 0.01), a highly selective suicide substrate inhibitor of iPLA(2).
      Following BEL, the ACh relaxation could be completely restored following
      pretreatment with picomolar quantities of the cell-permeant methyl ester analog
      of AA (arachidonic acid methyl ester, AA-Me). Higher amounts of AA-Me (1 microM)
      had a direct endothelium-dependent relaxing action, which was inhibited by the
      nitric-oxide synthase inhibitor (N(omega)-nitro-L-arginine; 100 microM),
      independent of ACh, and unaffected by BEL. Neither the ACh relaxation restoring
      action nor the direct relaxing action of AA-Me was affected by preincubation with
      inhibitors of the lipoxygenase (esculetin, 10 microM) or cytochrome P450
      monooxygenase (17-octadecynoic acid; 10 microM) pathways; and both actions of AA
      Me were enhanced following preincubation with the cyclooxygenase inhibitor
      indomethacin (10 microM; p < 0.05). The results of the present study indicate
      that iPLA(2)-produced AA plays an essential role in ACh-mediated endothelium
      dependent relaxation in rat mesenteric resistance arteries.

PMID- 12183648
TI  - The signal transduction of endothelin-1-induced circular smooth muscle cell
      contraction in cat esophagus.
AB  - It has been known that endothelin-1 (ET-1) exerts important actions in
      gastrointestinal smooth muscle motility, but its precise mechanism remains
      unsolved. We investigated the intracellular mechanism of ET-1-induced circular
      smooth muscle cell contraction in cat esophagus. ET-1 produced contraction of
      smooth muscle cells isolated by enzymatic digestion. The contraction in response
      to ET-1 was concentration-dependent. Pertussis toxin (PTX) blocked contraction
      induced by ET-1 in intact cells. To identify the specific G protein involved in
      the contraction, muscle cells were permeabilized with saponin. The G(i3) or
      G(beta) protein antibody inhibited the contraction. Neomycin phospholipase C
      (PLC) inhibitor inhibited the contraction, but 7,7-dimethyleicosadienoic acid
      (phospholipase A(2) inhibitor) and p-chloromercuribenzoic acid (phospholipase D
      inhibitor) had no effects. Incubation of permeabilized cells with PLC-beta(3)
      isozyme antibody inhibited the contraction. 1-(5-Isoquinolinesulfonyl)-2
      methylpiperazine, chelerythrine [protein kinase C (PKC) inhibitor], or genistein
      (protein tyrosine kinase inhibitor) inhibited the contraction, but not by
      diacylglycerol (DAG) kinase inhibitor, R59949. To test whether the contraction
      may be PKC isozyme-specific, we examined the effect of PKC isozymes antibodies on
      the contraction. PKC-epsilon antibody inhibited the contraction. To characterize
      further the specific PKC isozymes that mediate the contraction, we used, as an
      inhibitor, N-myristoylated peptides (myr-PKC) derived from the pseudosubstrate
      sequences of PKC-alphabetagamma, -alpha, -delta, or -epsilon. myr-PKC-epsilon
      inhibited the contraction, confirming that PKC-epsilon isozyme is involved in the
      contraction. To examine whether mitogen-activated protein kinases (MAPKs) mediate
      the contraction, specific MAPK inhibitors [MAPK kinase inhibitor, PD98059, (2'
      amino-3'-methoxy-flavone), and p38 MAPK inhibitor, SB202190 (4-4-fluorophenyl) 2
      (4-hydroxyphenyl)-5-(4-pyridyl)1H-imidazole)] were used. PD98059 or SB202190
      blocked the contraction. ET-1 increased the intensity of the detection bands
      identified by immunological methods as MAPK monoclonal p44/p42 peptides. PD98059
      decreased the intensity of the detection bands compared with ET-1. In conclusion,
      ET-1-induced contraction in cat esophageal circular muscle cells depends on PTX
      sensitive G(i3) protein and PLC-beta(3) isozyme, resulting in the activation of
      PKC-epsilon- or protein-tyrosine kinase-dependent pathway, subsequently mediating
      the activation of p44/p42 MAPK or p38 MAPK pathway.

PMID- 12183649
TI  - Chronic self-administration of nicotine in rats impairs T cell responsiveness.
AB  - Chronic exposure of rodents to nicotine via subcutaneously or
      intracerebroventricularly implanted miniosmotic pumps affects T cell function.
      However, this method of continuous nicotine administration does not replicate the
      self-motivated administration of nicotine in human smokers. To determine whether
      nicotine impairs the immune system under conditions pertinent to human smokers,
      we investigated the T cell responsiveness of male Lewis rats self-administering
      (SA) nicotine (0.03 mg/kg of body weight per injection) 40 to 50 times/day for 5
      weeks, using a model of virtually unlimited access to nicotine. Compared with
      sham control animals, the concanavalin A-induced proliferation of spleen cells
      from SA rats was significantly decreased. Moreover, the ability of spleen cells
      to mobilize intracellular Ca(2+) after ligation of the T cell antigen receptor
      (TCR) with an anti-alphabeta TCR antibody was significantly less in SA than in
      control rats. In addition, inositol 1,4,5-trisphosphate (IP(3))-sensitive
      intracellular Ca(2+) stores were markedly depleted in spleen cells from SA
      animals. These results suggest that chronic nicotine self-administration
      suppresses T cell responsiveness, and this suppression may result from an
      impaired TCR-mediated signaling that stems from the depletion of IP(3)-sensitive
      intracellular Ca(2+) stores.

PMID- 12183651
TI  - Significance of vascular endothelial cell growth factor up-regulation mediated
      via a chymase-angiotensin-dependent pathway during angiogenesis in hamster sponge
      granulomas.
AB  - Chymase is a serine protease responsible for local production of angiotensin
      (Ang) II from its precursor Ang I in several species, including humans, dogs, and
      hamsters. We have previously reported that chymase facilitates angiogenesis in
      sponge granulation tissues via local production of Ang II. Herein, we report the
      significance of vascular endothelial growth factor (VEGF) up-regulation mediated
      by Ang II during angiogenesis in hamster sponge granulomas. Treatment of
      granulation tissues with an anti-VEGF neutralizing antibody or antisense
      oligomers against VEGF mRNA significantly reduced Ang II-induced angiogenesis,
      supporting a significant role for VEGF during angiogenesis. In cultured
      fibroblasts prepared from granulation tissues, VEGF mRNA was up-regulated in
      response to Ang II within 2 h and this enhanced expression was abolished in the
      presence of an Ang II type 1 receptor-selective antagonist, an inhibitor of
      nuclear factor-kappaB activation, or an activator protein-1 inhibitor. To study
      the significance of local production of Ang II by chymase, we examined the
      effects of chymostatin on in vivo angiogenesis. We found that chymostatin
      markedly inhibited both up-regulation of VEGF mRNA and angiogenesis in
      granulation tissues treated by compound 48/80 or basic fibroblast growth factor.
      Our results suggest that Ang II directly acts on fibroblasts in granulation
      tissue to up-regulate VEGF mRNA and thereby induce angiogenesis. Furthermore, a
      chymase-Ang II-VEGF pathway may operate in granulation tissue as the primary
      mediator of angiogenesis.

PMID- 12183650
TI  - Pharmacological characterization of Ro 63-1908 (1-[2-(4-hydroxy-phenoxy)-ethyl]-4
      (4-methyl-benzyl)-piperidin-4-ol), a novel subtype-selective N-methyl-D-aspartate
      antagonist.
AB  - Ro 63-1908, 1-[2-(4-hydroxy-phenoxy)-ethyl]-4-(4-methyl-benzyl)-piperidin-4-ol,
      is a novel subtype-selective N-methyl-D-aspartate (NMDA) antagonist that has been
      characterized in vitro and in vivo. Ro 63-1908 inhibited [(3)H]dizocilpine ((3)H
      MK-801) binding in a biphasic manner with IC(50) values of 0.002 and 97 microM
      for the high- and low-affinity sites, respectively. Ro 63-1908 selectively
      blocked recombinant receptors expressed in Xenopus oocytes containing NR1C + NR2B
      subunits with an IC(50) of 0.003 microM and those containing NR1C + NR2A subunits
      with an IC(50) of >100 microM, thus demonstrating greater than 20,000-fold
      selectivity for the recombinant receptors expressing NR1C + NR2B. Ro 63-1908
      blocked these NMDA NR2B-subtype receptors in an activity-dependent manner. Ro 63
      1908 was neuroprotective against glutamate-induced toxicity and against
      oxygen/glucose deprivation-induced toxicity in vitro with IC(50) values of 0.68
      and 0.06 microM, respectively. Thus, the in vitro pharmacological
      characterization demonstrated that Ro 63-1908 was a potent and highly selective
      antagonist of the NR2B subtype of NMDA receptors. Ro 63-1908 was active against
      sound-induced seizures (ED(50) = 4.5 mg/kg i.p. when administered 30 min
      beforehand) in DBA/2 mice. The dose required to give a full anticonvulsant effect
      did not produce a deficit in the Rotarod test. NMDA-induced seizures were also
      inhibited by Ro 63-1908 with an ED(50) of 2.31 mg/kg i.v. when administered 15
      min before testing. Ro 63-1908 gave a dose-related neuroprotective effect against
      cortical damage in a model of permanent focal ischemia. Maximum protection of 39%
      was seen at a plasma concentration of 450 ng/ml. There were, however, no adverse
      cardiovascular or CNS side-effects seen at this dosing level.

PMID- 12183652
TI  - Rapid desensitization of the serotonin(2C) receptor system: effector pathway and
      agonist dependence.
AB  - The serotonin(2C) (5-HT(2C)) receptor couples to multiple effector mechanisms,
      including phospholipase A(2)-mediated arachidonic acid (AA) release and
      phospholipase C-mediated production of inositol phosphates (IP). Agonist relative
      efficacy differs depending upon which response (AA release or IP accumulation) is
      measured. In this study, we investigated the characteristics and agonist
      dependence of rapid desensitization of 5-HT(2C) receptor-mediated AA release and
      IP accumulation measured simultaneously from the same cell population.
      Pretreatment with 5-HT reduced the ability of a maximal concentration of 5-HT to
      elicit AA release and IP accumulation by about 60%; however, the AA response
      desensitized more rapidly (t(1/2) = 1.3 min) than the IP response (t(1/2) = 6.9
      min). In addition, desensitization of the IP response was more sensitive
      (occurred at lower receptor occupancy levels) than the AA response. Moreover, in
      response to submaximal 5-HT concentrations, after an initial transient
      desensitization, the AA response was enhanced by up to approximately 250%. After
      maximal desensitization, both responses recovered, but recovery of the AA
      response was complete and faster than that for IP. Desensitization of both
      responses was also agonist-dependent, and the capacity of agonists to elicit
      desensitization was not related to their efficacy to activate signaling. These
      data suggest that desensitization of the 5-HT(2C) receptor system is both agonist
      and effector pathway-dependent and underscore the need to study multiple
      cellular responses to multiple agonists to understand receptor-mediated signaling
      systems.

PMID- 12183653
TI  - Selective inhibition of P-glycoprotein expression in multidrug-resistant tumor
      cells by a designed transcriptional regulator.
AB  - Selective inhibition of the multidrug resistance 1 (MDR1) gene and its product,
      the P-glycoprotein, a membrane transporter responsible for multidrug resistance,
      could be an important approach for enhancing cancer therapeutics. An emerging
      strategy for selective gene regulation involves designed zinc finger proteins
      that can recognize specific sequences in the promoter regions of disease-related
      genes. Herein, we investigate the behavior of clones of multidrug-resistant
      NCI/ADR-RES breast carcinoma cells displaying ponasterone-inducible expression of
      a designed transcriptional repressor targeted to the MDR1 promoter. The
      controlled production of this novel repressor resulted in major reductions in P
      glycoprotein levels in these otherwise highly drug-resistant tumor cells. The
      regulated reduction of MDR1 expression in NCI/ADR-RES cells was accompanied by a
      marked increase in the rate of uptake of the P-glycoprotein substrate rhodamine
      123. In addition, the cytotoxicity profile of the antitumor drug doxorubicin was
      dramatically altered in the induced cells compared with controls. The expression
      levels of other genes were examined both by a DNA array analysis of approximately
      2000 genes and by biochemical techniques. Although some changes were observed in
      mRNA levels of nontargeted genes, the most dramatic effect by far was on MDR1,
      indicating that the action of the designed transcriptional repressor was quite
      selective. This study suggests that designed transcriptional regulators can be
      used to strongly and selectively influence expression of cancer-related genes,
      even under circumstances of extensive amplification of the target gene.

PMID- 12183654
TI  - Pituitary adenylate cyclase-activating polypeptide induces a sustained increase
      in intracellular free Ca(2+) concentration and catechol amine release by
      activating Ca(2+) influx via receptor-stimulated Ca(2+) entry, independent of
      store-operated Ca(2+) channels, and voltage-dependent Ca(2+) channels in bovine
      adrenal medullary chromaffin cells.
AB  - Characteristics of pituitary adenylate cyclase-activating polypeptide (PACAP)
      induced increase of Ca(2+) entry and catecholamine (CA) release were studied in
      bovine adrenal medullary chromaffin cells. PACAP induced intracellular free
      Ca(2+) concentration ([Ca(2+)](i)), showing an initial transient [Ca(2+)](i) rise
      followed by a sustained rise and CA release, which were not blocked by the
      blocking agents for nicotinic acetylcholine receptor (nAChR) channel, the voltage
      dependent Ca(2+) channel (VOC), or the Na(+) channel. The sarcoendoplasmic Ca(2+)
      ATPase inhibitors thapsigargin and cyclopiazonic acid did not affect the PACAP
      induced sustained rise of [Ca(2+)](i), but did inhibit the initial [Ca(2+)](i)
      rise. In cells pretreated with cyclopiazonic acid or membrane-permeable, low
      affinity Ca(2+) chelator N',N',N',N'-tetrakis(2-pyridylmethyl)ethylenediamine,
      PACAP further stimulated the entry of Ca(2+) or Mn(2+), whereas these treatments
      masked [Ca(2+)](i) dynamics induced by bradykinin. PACAP-induced sustained
      [Ca(2+)](i) rise and Mn(2+) entry were enhanced by acidic extracellular solution
      and reduced by alkalinization, whereas thapsigargin-induced Mn(2+) entry was
      regulated by the opposite. PACAP-induced [Ca(2+)](i) rise and Mn(2+) entry were
      not affected by blockers of cAMP-dependent protein kinase, phospholipase C, or
      protein kinase C. All store-operated Ca(2+) channel (SOC) blocking agents tested
      inhibited thapsigargin-induced Mn(2+) entry. 1(beta-[3-(4-Methoxyphenyl)-propoxy]
      4-methoxyphenylethyl)-1H-imidazole hydrochloride (SK&F 96365), (R,S)-(3,4-dihydro
      6,7-dimethoxy-isoquinoline-1-yl)-2-phenyl-N,N-di-[2-(2,3,4
      trimethoxyphenyl)ethyl]-acetamide, and econazole inhibited PACAP-induced Ca(2+)
      or Mn(2+) entry, whereas GdCl(3), 7,8-benzoflavone, nor-dihydroguaiaretic acid, 5
      nitro-2-(3-phenylpropylamino)benzoic acid, fulfenamic acid, and niflumic acid did
      not. SK&F 96365 and econazole but not GdCl(3) inhibited PACAP-induced CA release.
      These results suggest that PACAP activates a novel Ca(2+) entry pathway
      associated with sustained CA release independent of the nAChR channel, VOC and
      SOC, activated by acid pH, with different sensitivity to blockers of SOC. This
      pathway may provide a useful model for the study of receptor-operated Ca(2+)
      entry.

PMID- 12183655
TI  - Effects of serotonin (5-hydroxytryptamine, 5-HT) reuptake inhibition plus 5
      HT(2A) receptor antagonism on the firing activity of norepinephrine neurons.
AB  - YM992 [(S)-2-[[(7-fluoro-4-indanyl)oxy]methyl]morpholine monohydrochloride] is a
      selective serotonin (5-hydroxytryptamine; 5-HT) reuptake inhibitor (SSRI) and a
      potent 5-HT(2A) antagonist. The aim of the present study was to assess, using in
      vivo extracellular unitary recordings, the effect of acute and sustained
      administration of YM992 (40 mg kg(-1) day(-1) s.c., using osmotic minipumps) on
      the spontaneous firing activity of locus coeruleus (LC) norepinephrine (NE)
      neurons. Acute intravenous injection of YM992 (4 mg kg(-1)) significantly
      decreased NE neuron firing activity by 29% and blocked the inhibitory effect of a
      subsequent injection of the 5-HT(2) agonist DOI [1-(2,5-dimethoxy-4-iodophenyl)-2
      aminopropane hydrochloride]. A 2-day treatment with YM992 decreased the firing
      rate of NE neurons by 66%, whereas a partial recovery was observed after a 7-day
      treatment and a complete one after a 21-day treatment. Following the injection of
      the alpha(2)-adrenoceptor antagonist idazoxan (1 mg kg(-1) i.v.), NE neuron
      firing was equalized in controls and 2-day YM992-treated rats. This put into
      evidence an increased degree of activation of alpha(2)-adrenergic autoreceptors
      in the treated rats. The suppressant effect of the alpha(2)-adrenoceptor agonist
      clonidine was significantly decreased in long-term YM992-treated rats. The
      recovery of LC firing activity after long-term YM992 administration could thus be
      explained by a decreased sensitivity of alpha(2)-adrenergic autoreceptors.
      Sustained SSRI administration leads to a gradual reduction of the firing activity
      of NE neurons during long-term administration, whereas YM992 produced opposite
      effects. The exact basis for the increased synaptic availability of NE by YM992
      remains to be elucidated. This NE activity, resulting from 5-HT reuptake
      inhibition plus 5-HT(2A) receptor antagonism, might confer additional benefits in
      affective and anxiety disorders.

PMID- 12183657
TI  - Differential effects of mu-opioid receptor ligands on Ca(2+) signaling.
AB  - Activation of mu-opioid receptors (MORs) transfected into human embryonic kidney
      293 cells, caused a multiphasic increase in cytosolic free Ca(2+) levels
      (Ca(2+)i). The first Ca(2+)i maximum (peak 1) between 5 and 7 s depended on the
      presence of extracellular Ca(2+) (Ca(2+)e). The second phase peaking at
      approximately 15 s (peak 2) was independent of Ca(2+)e and thus represents Ca(2+)
      release from intracellular stores. A decrease in temperature from 37 to 25
      degrees C also caused reduction of peak 1 but not peak 2, suggesting that the two
      responses arise from mechanistically distinct pathways. A delayed Ca(2+)e
      dependent third response phase is thought to represent capacitative Ca(2+)e
      influx evoked after release of Ca(2+) from internal stores. Agonists and
      antagonists of two major classes of opioid ligands, oxymorphinans (morphine and
      naloxone) and oripavines (etorphine and diprenorphine), had differential effects
      on Ca(2+) currents. Although morphine activated both phases with equal potency,
      etorphine was 20-fold less potent at stimulating peak 1 over peak 2. Similarly,
      the antagonists, naloxone and diprenorphine, blocked the Ca(2+) response to each
      agonist with greatly varying potencies. Specifically, concomitant injection of
      diprenorphine failed to affect peak 1 (thought to represent rapid Ca(2+)e influx)
      stimulated by morphine while fully blocking peak 2 (intracellular Ca(2+)
      release). However, diprenorphine potently inhibited peak 1 as well when added to
      the cells before morphine, indicating limited or slow access of diprenorphine to
      these morphine binding sites. The existence of multiple, functionally distinct
      binding site conformations could account for these findings. In conclusion,
      different opioid ligands can differentially affect Ca(2+) response patterns
      resulting from MOR activation.

PMID- 12183656
TI  - Enzyme kinetics and pharmacological characterization of nucleotidases released
      from the guinea pig isolated vas deferens during nerve stimulation: evidence for
      a soluble ecto-nucleoside triphosphate diphosphohydrolase-like ATPase and a
      soluble ecto-5'-nucleotidase-like AMPase.
AB  - Previously, we have demonstrated that stimulation of the sympathetic nerves of
      the guinea pig vas deferens evokes release not only of the cotransmitters ATP and
      norepinephrine but also of soluble nucleotidases that break down extracellular
      ATP, ADP, and AMP into adenosine. In this study we show that the apparent K(m)
      values of the releasable enzyme activity vary depending on which of these adenine
      nucleotides is used as initial substrate. The K(m) value for ATP was 33.6 +/- 2.3
      microM, 21.0 +/- 2.3 microM for ADP, and 10.0 +/- 1.1 microM for AMP. The ratios
      of the V(max) values for each enzyme reaction were 4:2:3. We have also found a
      different sensitivity of the metabolism of ATP and AMP by releasable
      nucleotidases to known nucleotidase inhibitors. Suramin inhibited the breakdown
      of ATP by releasable nucleotidases in a noncompetitive manner and with a K(i)
      value of 53 microM, but had no effect on the breakdown of AMP. The 5'
      nucleotidase inhibitor alpha,beta-methylene ADP inhibited the breakdown of AMP
      but not that of ATP. Concanavalin A inhibited the breakdown of AMP but had
      neither inhibitory nor facilitatory effects on the breakdown of ATP. 6-N,N
      Diethyl-beta,gamma-dibromomethylene-D-ATP (ARL67156), an ecto-ATPase inhibitor,
      suppressed ATPase and AMPase activities, whereas NaN(3) (10 mM) affected neither
      reaction, but inhibited the ADP metabolism. Phosphatase- and phosphodiesterase
      inhibitors did not affect the activity of the releasable nucleotidases. This
      evidence suggests that the soluble nucleotidases released during neurogenic
      stimulation of the guinea pig vas deferens combine an ecto-5'-nucleotidase-like
      and an ecto-nucleoside triphosphate diphosphohydrolase-like activity.

PMID- 12183658
TI  - Pregabalin (CI-1008) inhibits the trinitrobenzene sulfonic acid-induced chronic
      colonic allodynia in the rat.
AB  - In human, digestive disorders are often associated with visceral pain. In these
      pathologies, visceral pain threshold is decreased indicating a visceral
      hypersensitivity. Pregabalin [CI-1008; S-(+)-3-isobutylgaba] presents
      antihyperalgesic actions in inflammatory somatic pain models. This study was
      designed to evaluate 1) the effect of injection of TNBS into the colon on
      visceral pain threshold, and 2) the antihyperalgesic effect of pregabalin on TNBS
      induced chronic colonic allodynia. A significant decrease in the colonic pain
      threshold was observed in trinitrobenzene sulfonic acid (TNBS)-treated animals
      (17.8 +/- 1.27 versus 43.4 +/- 1.98 mm Hg). Pregabalin (30-200 mg/kg s.c.) and
      morphine (0.1-1 mg/kg s.c.) showed a dose-related inhibition of TNBS-induced
      colonic allodynia. Pregabalin did not inhibit the colonic inflammatory effect of
      TNBS. In normal conditions (control animals), morphine (0.3 mg/kg s.c.)
      significantly increased the colonic pain threshold, whereas pregabalin (200 mg/kg
      s.c.) did not modify the colonic pain threshold. Pregabalin suppressed the TNBS
      induced colonic allodynia but did not modify the colonic threshold in normal
      conditions. The ability of pregabalin to block the chronic colonic allodynia
      indicates that it is effective in abnormal colonic hypersensitivity, suggesting a
      possible effect in chronic pain in irritable bowel syndrome.

PMID- 12183659
TI  - Proteolysis of the N-methyl-d-aspartate receptor by calpain in situ.
AB  - N-Methyl-D-aspartate (NMDA) receptors are calcium-permeable glutamate receptors
      that play putative roles in learning, memory, and excitotoxicity. NMDA receptor
      mediated calcium entry can activate the calcium-dependent protease calpain,
      leading to substrate degradation. The major NMDA receptor 2 (NR2) subunits of the
      receptor are in vitro substrates for calpain at selected sites in the C-terminal
      region. In the present study, we assessed the ability of calpain-mediated
      proteolysis to modulate the NR1a/2A subtype in a heterologous expression system.
      Human embryonic kidney (HEK293t) cells, which endogenously express calpain, were
      cotransfected with NR1a/2A in addition to the calpain inhibitor calpastatin or
      empty vector as control. Receptor activation by glutamate and glycine as co
      agonists led to calpain activation as measured by succinyl-L-leucyl-L-leucyl-L
      valyl-L-tyrosyl-aminomethyl coumarin (Suc-LLVY-AMC). Calpain activation also
      resulted in the degradation of NR2A and decreased binding of (125)I-MK-801
      ((125)I-dizocilpine) to NR1a/2A receptors. No stable N-terminal fragment of the
      NMDA receptor was formed after calpain activation, suggesting calpain regulation
      of NMDA receptor levels in ways distinct from that previously observed with in
      vitro cleavage. NR2 subunit constructs lacking the final 420 amino acids were not
      degraded by calpain. Agonist-stimulated NR1a/2A-transfected cells also had
      decreased calcium uptake and produced lower changes in agonist-stimulated
      intracellular calcium compared with cells cotransfected with calpastatin.
      Calpastatin had no effect on either calcium uptake or intracellular calcium
      levels when the NR2A subunit lacked the final 420 amino acids. These studies
      demonstrate that NR2A is a substrate for calpain in situ and that this
      proteolytic event can modulate NMDA receptor levels.

PMID- 12183660
TI  - Distinct roles for cyclooxygenases 1 and 2 in interleukin-1-induced behavioral
      changes.
AB  - Interleukin-1 (IL-1) induces hypophagia, which can be reduced by cyclooxygenase
      (COX) inhibitors. Earlier studies with COX knockout (COXko) mice suggested that
      COX2 was more important for hypophagia than COX1. However, behavioral responses
      occur long before COX2 is induced. Hypophagia was assessed in mice by measuring
      the intake of sweetened milk in a brief period. The intake was reduced within 30
      min after intraperitoneal injection of IL-1beta and was depressed for about 2 h.
      When milk intake was measured 30 to 40 min after IL-1beta, COX1ko mice showed an
      attenuated response, whereas COX2ko mice responded more like wild-type animals.
      By contrast, 90 to 120 min after IL-1beta COX1ko mice responded normally, whereas
      COX2ko mice showed only small responses. The COX2-selective inhibitor, celecoxib,
      failed to alter the response to IL-1beta 30 min after administration, but low
      doses antagonized the effects of IL-1beta at 90 to 120 min. The COX1-selective
      inhibitor, SC560, attenuated both the early and late responses, but a larger
      effect at 30 min than at 90 min suggested a role for COX1 at the earlier time.
      These results suggest that shortly after IL-1beta administration, COX1 is the
      major enzyme involved in the reduction of milk intake, whereas at later times
      COX2 is more important, paralleling its induction. Celecoxib also attenuated the
      milk intake response observed 2 h after lipopolysaccharide (LPS), and the
      reductions of food pellet intake and body weight induced by IL-1beta and LPS in
      the subsequent 24 h, suggesting that the role of COX2 may be more significant
      biologically than that of COX1.

PMID- 12183662
TI  - Proteinase-activated receptor 2: differential activation of the receptor by
      tethered ligand and soluble peptide analogs.
AB  - Activation of rat proteinase-activated receptor 2 (PAR2) by trypsin involves the
      unmasking of the tethered sequence S(37)LIGRL(42) that either tethered or on its
      own as a free peptide, activates PAR2. We aimed to determine whether different
      peptide sequences acting either as trypsin-revealed tethered ligands or as
      soluble peptides had the same relative activities for triggering the receptor. A
      comparison was also made between the different soluble and tethered receptor
      activating sequences in receptor constructs with extracellular loop 2 (ECL2)
      residues E(232)E(233) (PAR2SR/EE) mutated to R(232)R(233) (PAR2SR/RR). Using site
      directed mutagenesis, we prepared PAR2 constructs with trypsin-revealed tethered
      ligand sequences corresponding to the synthetic receptor-activating peptides
      (PAR2APs): SLIGRL-NH(2) (SR-NH(2)), SLIGAL-NH(2) (SA-NH(2)), and SLIGEL-NH(2) (SE
      NH(2)). Kirsten virus-transformed rat kidney cells stably expressing 1) wild-type
      PAR2 with site-mutated tethered ligands (PAR2SA/EE and PAR2SE/EE); 2) wild-type
      PAR2 with ECL2 mutated to R(232)R(233) (PAR2SR/RR); and 3) PAR2 constructs with
      both the RR mutation in ECL2 and a mutation in the tethered ligand (PAR2SA/RR and
      PAR2SE/RR) were assessed for receptor-mediated calcium signaling and cell growth
      inhibition, upon activation either by trypsin or the above-mentioned PAR2APs.
      Trypsin exerted equivalent and full agonist activity on the PAR2 constructs,
      causing a maximum response between 20 to 80 nM. In contrast, the PAR2APs as free
      peptide agonists showed marked potency differences in all wild-type receptors
      with mutated tethered ligands (SR-NH(2) >> SA-NH(2) >> SE-NH(2)) and in all ECL2
      RR mutated constructs (SE-NH(2) > SR-NH(2) >> SA-NH(2)). We conclude that for
      receptor activation, the trypsin-revealed PAR2 tethered ligand sequence interacts
      differently for receptor activation than does the same peptide sequence as a free
      peptide.

PMID- 12183661
TI  - Molecular and pharmacological characterization of GABA(A) receptor alpha1 subunit
      knockout mice.
AB  - GABA(A) receptors mediate fast inhibitory neurotransmission in the central
      nervous system (CNS), and approximately half of these receptors contain alpha1
      subunits. GABA(A) receptor alpha1 subunits are important for receptor assembly
      and specific pharmacological responses to benzodiazepines. Plasticity in GABA(A)
      receptor alpha1 subunit expression is associated with changes in CNS excitability
      observed during normal brain development, in animal models of epilepsy, and upon
      withdrawal from alcohol and benzodiazepines. To examine the role of alpha1
      subunit-containing GABA(A) receptors in vivo, we characterized receptor subunit
      expression and pharmacological properties in cerebral cortex of knockout mice
      with a targeted deletion of the alpha1 subunit. The mice are viable but exhibit
      an intention tremor. Western blot analysis confirms the complete loss of alpha1
      subunit peptide expression. Stable adaptations in the expression of several
      GABA(A) receptor subunits are observed in the fifth to seventh generations,
      including decreased expression of beta2/3 and gamma2 subunits and increased
      expression of alpha2 and alpha3 subunits. There was no change in alpha4, alpha5,
      or delta subunit peptide levels in cerebral cortex. Knockout mice exhibit loss of
      over half of GABA(A) receptors measured by [(3)H]muscimol, [(3)H]2-(3-carboxyl)-3
      amino-6-(4-methoxyphenyl)-pyridazinium bromide ([(3)H]SR-95531), and t
      butylbicyclophosphoro[(35)S]thionate ([(35)S]TBPS) binding. [(3)H]Ethyl-8-azido
      5,6-dihydro-5-methyl-6-oxo-4H-imidazo[1,5-a][1,4]benzodiazepine-3-carboxylate
      ([(3)H]Ro15-4513) binding is reduced by variable amounts in different regions
      across brain. GABA(A) receptor alpha1(-/-) mice lose all high-affinity
      [(3)H]zolpidem binding and about half of [(3)H]flunitrazepam binding in the
      cerebral cortex. The potency and maximal efficacy of muscimol-stimulated (36)Cl(
      ) uptake in cerebral cortical synaptoneurosomes are reduced in alpha1(-/-) mice.
      Furthermore, knockout mice exhibit increased bicuculline-induced seizure
      susceptibility compared with wild-type mice. These data emphasize the
      significance of alpha1 subunit expression and its involvement in the regulation
      of CNS excitability.

PMID- 12183663
TI  - Novel antiangiogenic effects of the bisphosphonate compound zoledronic acid.
AB  - Bisphosphonate drugs inhibit osteoclastic bone resorption and are widely used to
      treat skeletal complications in patients with tumor-induced osteolysis. We now
      show that zoledronic acid, a new generation bisphosphonate with a heterocyclic
      imidazole substituent, is also a potent inhibitor of angiogenesis. In vitro,
      zoledronic acid inhibits proliferation of human endothelial cells stimulated with
      fetal calf serum, basic fibroblast growth factor (bFGF), and vascular endothelial
      growth factor (IC(50) values 4.1, 4.2, and 6.9 microM, respectively), and
      modulates endothelial cell adhesion and migration. In cultured aortic rings and
      in the chicken egg chorioallantoic membrane assay, zoledronic acid reduces vessel
      sprouting. When administered systemically to mice, zoledronic acid potently
      inhibits the angiogenesis induced by subcutaneous implants impregnated with bFGF
      [ED(50), 3 microg/kg (7.5 nmol/kg) s.c.]. These findings indicate that zoledronic
      acid has marked antiangiogenic properties that could augment its efficacy in the
      treatment of malignant bone disease and extend its potential clinical use to
      other diseases with an angiogenic component.

PMID- 12183664
TI  - Differential transport of a secretin analog across the blood-brain and blood
      cerebrospinal fluid barriers of the mouse.
AB  - Secretin is a gastrointestinal peptide belonging to the vasoactive intestinal
      peptide (VIP)/glucagon/pituitary adenylate cyclase-activating polypeptide (PACAP)
      family recently suggested to have therapeutic effects in autism. A direct effect
      on brain would require secretin to cross the blood-brain barrier (BBB), an
      ability other members of the VIP/PACAP family have. Herein, we examined whether a
      secretin analog (SA) radioactively labeled with (131)I (I-SA) could cross the BBB
      of 4-week-old mice. We found I-SA was rapidly cleared from serum with fragments
      not precipitating with acid appearing in brain and serum. Levels of radioactivity
      were corrected to reflect only intact I-SA as estimated by acid precipitation.
      After i.v. injection, I-SA was taken up by brain at a modest rate of 0.9 to 1.5
      microl/g-mm. Capillary depletion, brain perfusion, and high-performance liquid
      chromatography were used to confirm the passage of intact I-SA across the BBB. I
      SA entered every brain region, with the highest uptake into the hypothalamus and
      cerebrospinal fluid (CSF). Unlabeled SA (10 microg/mouse) did not inhibit uptake
      by brain but did inhibit clearance from blood and uptake by the CSF, colon,
      kidney, and liver. The decreased clearance of I-SA from blood increased the
      percentage of the i.v. injected dose taken up per brain (%Inj/g) from about 0.118
      to 0.295%Inj/g. In conclusion, SA crosses the vascular barrier by a nonsaturable
      process and the choroid plexus by a saturable process in amounts that for other
      members of its family produce central nervous system (CNS) effects. This passage
      provides a pathway through which peripherally administered SA could affect the
      CNS.

PMID- 12183665
TI  - Chronic agonist treatment converts antagonists into inverse agonists at delta
      opioid receptors.
AB  - In cellular models, chronic exposure to mu-opioid agonists converts antagonists
      into inverse agonists at mu-receptors. Such adaptations could contribute to the
      development of tolerance and/or dependence. To determine whether delta-receptors
      respond similarly, or whether this adaptation is unique for mu-receptors, this
      study examined the effects of prolonged agonist exposure on the intrinsic
      activity of several delta-opioid ligands in GH(3) cells expressing delta
      receptors. In opioid naive cells, delta-receptors were constitutively active, and
      a series of delta-ligands displayed a range of intrinsic activities for G protein
      activation. Chronic treatment with the full delta-agonist [D-Pen(2,5)]-enkephalin
      reduced the acute ability of [D-Pen(2,5)]-enkephalin to stimulate and the full
      inverse agonist N,N-diallyl-Tyr-Aib-Aib-Phe-Leu-OH (ICI-174864) to inhibit G
      protein activation. In contrast, although naloxone and naltriben exhibited weak
      partial agonism in opioid naive cells, both ligands acted as full inverse
      agonists to produce concentration-dependent inhibition of guanosine 5'-O-(3
      [(35)S]thio)triphosphate binding after prolonged exposure to [D-Pen(2,5)]
      enkephalin or to the partial agonist morphine. This effect was reversed by a
      neutral delta-antagonist (N,N-bisallyl)-Tyr-Gly-Gly-psi-(CH(2)S)-Phe-Leu-OH (ICI
      154129). Finally, as is also characteristic of inverse agonists, naloxone and
      naltriben demonstrated higher affinities for uncoupled delta-receptors in cells
      chronically treated with [D-Pen(2,5)]-enkephalin, relative to opioid naive cells.
      Therefore, this relatively novel adaptation is shared by both mu- and delta
      opioid receptors and therefore may serve as an important common mechanism
      involved the development of tolerance and/or dependence.

PMID- 12183666
TI  - Measurement of agonist-dependent and -independent signal initiation of alpha(1b)
      adrenoceptor mutants by direct analysis of guanine nucleotide exchange on the G
      protein galpha(11).
AB  - Immunoprecipitation of a fusion protein between the alpha(1b)-adrenoceptor and
      Galpha(11) following a [(35)S]GTPgammaS [guanosine-5'-O-(3-thio)triphosphate]
      binding assay resulted in incorporation of low levels of nucleotide. The agonist
      phenylephrine increased incorporation some 30-fold. Agonist-induced binding
      represented 1.0 mol of [(35)S]GTPgammaS/mol of fusion protein. This was to the G
      protein linked to the receptor rather than endogenous Galpha(q)/Galpha(11) as a
      fusion protein containing the alpha(1b)-adrenoceptor and a form of Galpha(11)
      (G(208)A) unable to exchange guanine nucleotides effectively, bound
      [(35)S]GTPgammaS very poorly. Fusion proteins between A(293)E, D(142)A, and 3CAM
      mutants of the alpha(1b)-adrenoceptor and Galpha(11) bound substantially greater
      levels of [(35)S]GTPgammaS in the absence of agonist than the fusion
      incorporating the wild-type receptor. Constitutive binding of the nucleotide
      induced by these mutants was only 20% of the level achieved by phenylephrine.
      These mutant receptors thus do not provide an accurate mimic of the agonist
      occupied state. Phentolamine reduced the binding of [(35)S]GTPgammaS and acted as
      a partial inverse agonist for each of the constitutively active mutants.
      [(35)S]GTPgammaS binding to Galpha(11) was elevated by phenylephrine in both wild
      type and constitutively active mutant forms of the fusion proteins, but agonist
      potency and binding affinity were 50 times higher for the fusions containing the
      mutated receptors. These studies provide the first direct demonstration of the
      capacity of constitutively active mutants of a receptor to stimulate guanine
      nucleotide exchange on the alpha subunit of a G(q) family G protein and defines a
      strategy potentially suitable for any receptor that couples to these G proteins.

PMID- 12183667
TI  - In vitro and in vivo characterization of the activity of telmisartan: an
      insurmountable angiotensin II receptor antagonist.
AB  - In vitro studies have shown that telmisartan is an insurmountable angiotensin II
      subtype-1 (AT1) receptor antagonist. Herein, the molecular basis of this
      insurmountable antagonism has been investigated in vitro, and the effect of
      telmisartan has been compared in vivo with that of irbesartan and candesartan.
      Association and dissociation kinetics of telmisartan to AT1 receptors have been
      characterized in vitro on rat vascular smooth muscle cells (RVSMC) expressing
      solely the AT1 receptor subtype. In a second set of experiments, the antagonistic
      efficacy of single intravenous doses (0.1, 0.3, and 1 mg/kg) of telmisartan was
      compared with that of irbesartan (0.3, 1.0, 3.0, and 10.0 mg/kg) and candesartan
      (0.3 and 1 mg/kg) in conscious, normotensive, male Wistar rats. The results show
      that the specific binding of [(3)H]telmisartan to the surface of living RVSMC is
      saturable and increases quickly to reach equilibrium within 1 h. Telmisartan
      dissociates very slowly from the receptor with a dissociation half-life (t(1/2))
      of 75 min, which is comparable with candesartan and almost 5 times slower than
      angiotensin II (AngII). In vivo, telmisartan blunts the blood pressure response
      to exogenous AngII dose dependently. The blockade is long lasting and remains
      significant at 24 h at doses >0.1 mg/kg. Ex vivo assessment of the AT1 receptor
      blockade using an in vitro AngII receptor binding assay shows similar results.
      When administered intravenously in rats, telmisartan is 10-fold more potent than
      irbesartan and comparable to candesartan. Taken together, our in vitro data show
      that the insurmountable antagonism of telmisartan is due at least in part to its
      very slow dissociation from AT1 receptors.

PMID- 12183668
TI  - Effect of P-glycoprotein on the pharmacokinetics and tissue distribution of
      enaminone anticonvulsants: analysis by population and physiological approaches.
AB  - Multidrug resistance (MDR), mediated by P-glycoprotein (Pgp) has been identified
      as altering the disposition of structurally diverse compounds. Previous in vitro
      studies in bovine brain microvascular endothelial cells and MCF/Adr [Adriamycin
      (doxorubicin)-resistant human breast cancer] cells displayed that the transport
      of enaminone anticonvulsants was influenced by Pgp. Therefore the objectives of
      this study was to further evaluate the influence of Pgp on the pharmacokinetics
      and tissue distribution of the enaminone analogs. mdr1ab (+/+) and mdr1ab (-/-)
      male mice (20 +/- 5 g) were administered DM5 (methyl 4-[(4'-chlorophenyl)amino]-6
      methyl-2-oxo-3-cyclohexene-1-carboxylate) or DM44 (12.5 mg/kg, i.v.). Cohorts (n
      = 3) were sacrificed over a 12-h period, and samples were analyzed by a validated
      UV-high performance liquid chromatography assay method. Population analysis was
      used to estimate pharmacokinetic parameters and partition coefficients were
      determined for tissues. The clearance (0.51 versus 0.33 l/h/kg) and V(d) (1.25
      versus 0.93 l/kg) of DM5 were found to be higher (p < 0.05), however the area
      under the curve (26.1 versus 38.2 microg/ml. h) was lower (p < 0.05) in mdr1a/1b
      (-/-) versus mdr1a/1b (+/+) mice, respectively. Similar findings were observed
      for DM44. Tissues known to express Pgp such as the heart, liver, lung, and brain
      displayed 2-fold or higher tissue levels in mdr1a/1b (-/-) versus mdr1a/1b (+/+)
      mice. These results strongly suggest that Pgp may influence enaminone tissue
      distribution and pharmacokinetics and may play a significant role in the
      effective treatment of epilepsy with these analogs.

PMID- 12183669
TI  - Increased dopamine receptor signaling and dopamine receptor-G protein coupling in
      denervated striatum.
AB  - Chronic interruption of the nigrostriatal dopaminergic pathway leads to
      sensitized dopaminergic responses in striatum. We attempted to explore the
      mechanism(s) underlying this dopaminergic supersensitivity by assessing dopamine
      receptor signaling and receptor-G protein coupling in unilateral 6
      hydroxydopamine-lesioned rats. Dopamine-stimulated adenylyl cyclase activity as
      well as dopamine-activated guanosine 5'-O-(3-[(35)S]thiotriphosphate)
      ([(35)S]GTPgammaS) binding and [(3)H]palmitate incorporation by Galpha proteins
      were enhanced in tissues obtained from denervated striata without apparent
      changes in Galpha protein levels. Moreover, high-affinity binding sites of the
      D(1) dopamine receptor increased in lesioned compared with control striata
      without altering the expression level of the receptor. These denervation-mediated
      changes appear to correlate with the increase in D(1) dopamine receptor binding
      sites that co-immunoprecipitated with Galphas(olf)/q(11) proteins. In contrast,
      the total number of D(2) receptor binding sites was increased, yielding an
      increase in absolute number of high-affinity sites without significant changes in
      the proportion of high-affinity sites. Stimulation of the D(2) dopamine receptor
      enhanced coupling to Galphai protein; this was increased in the striata lesioned.
      The results provide an important molecular mechanism by which dopamine receptor
      regulated signaling is enhanced following denervation of dopaminergic input to
      striatum. Although D(1) dopamine receptor supersensitivity appears to be mediated
      by enhanced coupling of the receptor to its G proteins, sensitization in the D(2)
      dopamine receptor system is mediated by increased D(2) receptor density and
      enhanced D(2) receptor-Gi protein coupling.

PMID- 12183670
TI  - Bupropion inhibits nicotine-evoked [(3)H]overflow from rat striatal slices
      preloaded with [(3)H]dopamine and from rat hippocampal slices preloaded with
      [(3)H]norepinephrine.
AB  - Bupropion, an efficacious antidepressant and smoking cessation agent, inhibits
      dopamine and norepinephrine transporters (DAT and NET, respectively). Recently,
      bupropion has been reported to noncompetitively inhibit alpha3beta2, alpha3beta4,
      and alpha4beta2 nicotinic acetylcholine receptors (nAChRs) expressed in Xenopus
      oocytes or established cell lines. The present study evaluated bupropion-induced
      inhibition of native alpha3beta2* and alpha3beta4* nAChRs using functional
      neurotransmitter release assays, nicotine-evoked [(3)H]overflow from superfused
      rat striatal slices preloaded with [(3)H]dopamine ([(3)H]DA), and nicotine-evoked
      [(3)H]overflow from hippocampal slices preloaded with [(3)H]norepinephrine
      ([(3)H]NE). The mechanism of inhibition was evaluated using Schild analysis. To
      eliminate the interaction of bupropion with DAT or NET, nomifensine or
      desipramine, respectively, was included in the superfusion buffer. A high
      bupropion concentration (100 microM) elicited intrinsic activity in the [(3)H]DA
      release assay. However, none of the concentrations (1 nM-100 microM) examined
      evoked [(3)H]NE overflow and, thus, were without intrinsic activity in this
      assay. Moreover, bupropion inhibited both nicotine-evoked [(3)H]DA overflow
      (IC(50) = 1.27 microM) and nicotine-evoked [(3)H]NE overflow (IC(50) = 323 nM) at
      bupropion concentrations well below those eliciting intrinsic activity. Results
      from Schild analyses suggest that bupropion competitively inhibits nicotine
      evoked [(3)H]DA overflow, whereas evidence for receptor reserve was obtained upon
      assessment of bupropion inhibition of nicotine-evoked [(3)H]NE overflow. Thus,
      bupropion acts as an antagonist at alpha3beta2* and alpha3beta4* nAChRs in rat
      striatum and hippocampus, respectively, across the same concentration range that
      inhibits DAT and NET function. The combination of nAChR and transporter
      inhibition produced by bupropion may contribute to its clinical efficacy as a
      smoking cessation agent.

PMID- 12183671
TI  - Close association between the reduction in myocardial energy metabolism and
      infarct size: dose-response assessment of cyclosporine.
AB  - Cyclosporine protects the heart against ischemia/reperfusion injury, but its
      effect on cardiac metabolism is largely unknown. We assessed cyclosporine-induced
      metabolic changes in the rat heart prior to occlusion using magnetic resonance
      spectroscopy (MRS) and correlated effects with infarct size in a coronary
      occlusion/reperfusion model. The two study groups were cyclosporine and
      cyclosporine + coronary occlusion (n = 20/group). Rats were pretreated with
      cyclosporine (5, 10, 15, and 25 mg/kg/day) or the vehicle by oral gavage for 3
      days (n = 4/dose). On day 4, hearts of rats in the cyclosporine group were
      excised, and extracted cell metabolites were measured using (1)H and (31)P MRS.
      The second group was subjected to 30 min of coronary artery occlusion followed by
      24 h of reperfusion. Infarct size and area at risk were measured using a double
      staining method. In the cyclosporine group, cyclosporine reduced cardiac energy
      metabolism (ATP: r = -0.89, P < 0.001) via depression of oxidative
      phosphorylation and the Krebs' cycle in a dose-dependent manner. The decrease of
      ATP levels was positively correlated with changes of NAD(+) (r = 0.89), glutamate
      (r = 0.95), glutamine (r = 0.84), and glucose concentrations (r = 0.92, all P <
      0.002). It was inversely correlated with lactate (r = -0.93, P < 0.001). In the
      coronary occlusion group, cyclosporine dose dependently reduced the ratio [area
      of infarct/area of the left ventricle] (r = -0.86, P < 0.01), with 15 mg/kg/day
      being the most effective cyclosporine dose. The reduction in infarct size
      correlated with the reduction in oxidative phosphorylation (ATP: r = 0.97;
      NAD(+): r = 0.82, P < 0.01). The reduction in cardiac energy metabolism before
      occlusion may be the cause of myocardial preservation during
      ischemia/reperfusion.

PMID- 12183672
TI  - The differential effects of atypical antipsychotics on prolactin elevation are
      explained by their differential blood-brain disposition: a pharmacological
      analysis in rats.
AB  - All atypical antipsychotics avoid extrapyramidal side-effects yet differ in their
      propensity to cause other side-effects, like prolactin elevation. We proposed
      that the atypical antipsychotics with a propensity for prolactin elevation would
      show a higher pituitary versus striatal D2 receptor occupancy. To investigate
      this hypothesis, we tested four atypical antipsychotics, two that are commonly
      associated with prolactin elevation (amisulpride and risperidone) and two that
      are less frequently associated (quetiapine and olanzapine). In particular, we
      calculated their ED(50) values to increase plasma prolactin and block peripheral
      pituitary D2 receptors to their ED(50) values to antagonize apomorphine-induced
      stereotypy and occupy central striatal D2 receptors. All antipsychotics dose
      dependently increased prolactin levels and antagonized apomorphine-induced
      stereotypy. However, the central to peripheral potency (ED(50) for apomorphine
      antagonism to ED(50) for prolactin elevation) differed remarkably across these
      drugs: amisulpride (21764), risperidone (14), quetiapine (10), and olanzapine
      (1.7). Compounds displaying a higher peripheral potency brought about higher
      prolactin levels for a given level of functional central antagonism. This
      dissociation between central and peripheral effects was explained by the
      differential occupancy of D2 receptors in the striatum versus in the pituitary
      [ratio of striatal/pituitary ED(50) values (milligram per kilogram) for D2
      occupancy): amisulpride (17/0.026 = 654), risperidone (0.89/0.081 = 14),
      quetiapine (24/4.1 = 6), olanzapine (0.30/0.43 = 0.7). These results indicate
      that dissociation between central and peripheral D2 receptor occupancy is a major
      determinant of the degree of prolactin elevation observed at therapeutic doses.

PMID- 12183673
TI  - Electrophysiological evidence for expression of glycine receptors in freshly
      isolated neurons from nucleus accumbens.
AB  - In the course of studying N-methyl-D-aspartate (NMDA) receptors of the nucleus
      accumbens (NAcc), we found that 20% of freshly isolated medium spiny neurons, as
      well as all interneurons, responded in an unexpected way to long (5-s)
      coapplication of NMDA and glycine, the coagonist of NMDA receptors. Whereas the
      reversal potential of the peak NMDA current of this subset of neurons was still
      around 0 mV, the desensitizing current became outward at hyperpolarized
      potentials around -30 mV. A Cl(-)-free solution shifted the equilibrium
      potentials of the desensitized currents to around 0 mV. This outward current was
      not blocked by a Ca(2+)-free, Ba(2+)-containing solution, suggesting that the
      anionic conductance was not activated by Ca(2+) influx through NMDA receptor
      channels. Interestingly, glycine alone also evoked a current with a similar
      hyperpolarized reversal potential in this subset of neurons. The glycine current
      reversed around -50 mV, rectified outwardly, and inactivated strongly. Its
      desensitization was best fitted with a double exponential. Only the slow
      desensitization showed clear voltage dependence. The glycine current was not
      blocked by 200 microM picrotoxin and 10 microM zinc, was weakly antagonized by 1
      microM strychnine, and was not enhanced by 1 microM zinc. In addition, 1 mM
      taurine, but not GABA, inactivated glycine currents, and 1 mM glycine occluded 10
      mM taurine-mediated currents. These data indicate that a subset of nucleus
      accumbens neurons expresses glycine receptors and that either glycine or taurine
      could be an endogenous agonist for these receptors.

PMID- 12183675
TI  - Fluticasone propionate inhibits lipopolysaccharide-induced proinflammatory
      response in human cystic fibrosis airway grafts.
AB  - Airway inflammation, one of the major factors leading to lung damage in cystic
      fibrosis (CF) patients, is associated with an abnormal increase in
      proinflammatory cytokines. In this work, we demonstrate the increased release of
      the proinflammatory cytokines after lipopolysaccharide (LPS) stimulation: human
      interleukin (hIL)-8 in CF and non-CF airway xenografts, and hIL-6 and human
      growth-related oncogene-alpha (hGRO-alpha), which could be only analyzed in non
      CF xenografts. Under basal conditions, we observed that hIL-8 was higher in CF
      xenografts compared with non-CF. We also report the anti-inflammatory effect of a
      glucocorticoid, fluticasone propionate (FP), on CF airway epithelium using a
      humanized model of airway inflammation developed in nude mice. In CF and non-CF
      tracheal xenografts, airway inflammation was induced by inoculating Pseudomonas
      aeruginosa LPS (4 h; 1 microg/ml) in the lumen of the xenografts. FP pretreatment
      (2 h; 10(-8) M) followed by P. aeruginosa LPS stimulation induced a significant
      reduction of LPS-induced hIL-8 release in airway liquid collected from CF and non
      CF tracheal xenografts (85 and 80%, respectively). In non-CF tracheal xenografts,
      FP treatment before LPS stimulation induced a significant decrease in hIL-6 and
      hGRO-alpha. From these data, we suggest that FP exerts anti-inflammatory
      properties that may be appropriate to CF therapy, at an early stage of the
      disease. In addition, these results demonstrate that the humanized airway model
      of inflammation provides a relevant tool for analyzing the effects of anti
      inflammatory drugs in different diseases in which airway inflammation is
      implicated.

PMID- 12183674
TI  - Chronic muscle pain induced by repeated acid Injection is reversed by spinally
      administered mu- and delta-, but not kappa-, opioid receptor agonists.
AB  - Opioids are commonly used for pain relief clinically and reduce hyperalgesia in
      most animal models. Two injections of acidic saline into one gastrocnemius muscle
      5 days apart produce a long-lasting bilateral hyperalgesia without associated
      tissue damage. The current study was undertaken to assess the effects of opioid
      agonists on mechanical hyperalgesia induced by repeated intramuscular injections
      of acid. Morphine (mu-agonist), [D-Ala(2),N-Me-Phe(4),Gly-ol(5)]-enkephalin (mu
      agonist; DAMGO), 4-[((alpha)R)-alpha-((2S,5R)-4-allyl-2,5-dimethyl-1-piperazinyl)
      3-methoxybenzyl]-N,N-diethylbenzamide (delta-agonist; SNC80), or (1S-trans)-3,4
      dichloro-N-methyl-N-[2-(1-pyrrolidinyl)cylcohexyl]-benzeneacetamide hydrochloride
      (kappa-agonist; U50,488) were administered intrathecally to activate opioid
      receptors once hyperalgesia was developed. Mechanical hyperalgesia was assessed
      by measuring the withdrawal thresholds to mechanical stimuli (von Frey filaments)
      before the first and second intramuscular injection, 24 h after the second
      intramuscular injection, and for 1 h after administration of the opioid agonist
      or vehicle. Morphine, DAMGO, and SNC80 dose dependently increased the mechanical
      withdrawal threshold back toward baseline responses. The reduction in
      hyperalgesia produced by morphine and DAMGO was prevented by H-D-Phe-Cys-Tyr-D
      Trp-Arg-Thr-Pen-Thr-NH(2) (CTAP) and that of SNC80 was prevented by naltrindole.
      U50,488 had no effect on the decreased mechanical withdrawal thresholds. Thus,
      activation of mu- and delta-, but not kappa-, opioid receptors in the spinal cord
      reduces mechanical hyperalgesia following repeated intramuscular injection of
      acid, thus validating the use of this new model of chronic muscle pain.

PMID- 12183676
TI  - Mechanism-based pharmacokinetic-pharmacodynamic modeling of concentration
      dependent hysteresis and biphasic electroencephalogram effects of alphaxalone in
      rats.
AB  - The neuroactive steroid alphaxalone reveals a complex biphasic concentration
      effect relationship using the 11.5 to 30 Hz frequency band of the
      electroencephalogram (EEG) as biomarker. The purpose of the present investigation
      was to develop a mechanism-based pharmacokinetic-pharmacodynamic model to
      describe this observation. The proposed model is based on receptor theory and
      aims to separate the drug-receptor interaction from the transduction of the
      initial stimulus into the observed biphasic response. Individual concentration
      time courses of alphaxalone were obtained in combination with continuous
      recording of the EEG parameter. Alphaxalone was administered intravenously in
      various dosages. The pharmacokinetics were described by a two-compartment model,
      and parameter estimates for clearance, intercompartmental clearance, volume of
      distribution 1 and 2 were 158 +/- 29 ml. min(-1). kg(-1), 143 +/- 31 ml. min(-1).
      kg(-1), 122 +/- 20 ml. kg(-1) and 606 +/- 48 ml. kg(-1), respectively.
      Concentration-effect relationships exhibited a biphasic pattern and delay in
      onset of effect. The hysteresis was described on the basis of an effect
      compartment model with C(max) as covariate. The pharmacodynamic model consisted
      of a receptor model, featuring a monophasic saturable receptor activation model
      in combination with a biphasic stimulus-response model. The in vivo affinity
      (K(PD)) was estimated at 432 +/- 26 ng. ml(-1). Unique parameter estimates were
      obtained that were independent of the dose and the duration of the infusion. In
      conclusion, we have shown that this mechanism-based approach, which separates
      drug- and system-related properties in vivo, was successfully applied for the
      characterization of the biphasic effect versus time patterns of alphaxalone. The
      model should be of use in the characterization of other biphasic responses.

PMID- 12183677
TI  - Comparison of antiepileptic drugs tiagabine, lamotrigine, and gabapentin in mouse
      models of acute, prolonged, and chronic nociception.
AB  - Some antiepileptic drugs have been shown to be clinically effective in the
      treatment of neuropathic pain. This study determined whether the new
      antiepileptic drug tiagabine, a GABA uptake inhibitor, is efficacious in mice in
      a broad range of nociceptive tests (hot-plate, formalin, and dynorphin-induced
      chronic allodynia) and compared tiagabine's potency with two other antiepileptic
      drugs, gabapentin and lamotrigine. Intraperitoneally administered tiagabine, but
      not lamotrigine, gabapentin, or i.t. tiagabine, produced dose-dependent
      antinoception in the hot-plate test. A 5-min pretreatment with tiagabine (2-29
      nmol i.t.) dose-dependently inhibited both the acute and late phase formalin
      behaviors; pretreatment with lamotrigine (4-265 nmol i.t.) inhibited only the
      late phase. In the formalin assay the GABA(A) antagonist bicuculline reversed the
      acute phase antinociception, whereas the GABA(B) antagonist saclofen reversed
      both the acute and late phase tiagabine-induced antinociception. Tiagabine
      administered i.p. but not i.t. dose-dependently reduced dynorphin-induced chronic
      allodynia for 120 min. Gabapentin and lamotrigine produced antinociception
      administered either i.t. or i.p. in a dose-dependent manner. Thus, we have shown
      that gabapentin and lamotrigine produced antinociception in two mouse models of
      pain, whereas tiagabine produced antinociception in all three mouse models of
      pain.

PMID- 12183678
TI  - Methyl-laudanosine: a new pharmacological tool to investigate the function of
      small-conductance Ca(2+)-activated K(+) channels.
AB  - Small-conductance Ca(2+)-activated K(+) channels (SK channels) underlie the
      prolonged postspike afterhyperpolarization (AHP) observed in many central neurons
      and play an important role in modulating neuronal activity. However, a lack of
      specific and reversible blockers of these channels hampers their study in various
      experimental conditions. Because previous work has shown that bicuculline salts
      block these channels, we examined whether related alkaloids, namely laudanosine
      quaternary derivatives, would produce similar effects. Intracellular recordings
      were performed on rat midbrain dopaminergic neurons and hippocampus CA1 pyramidal
      cells. Binding experiments were performed on rat cerebral cortex membranes.
      Laudanosine, methyl-laudanosine, and ethyl-laudanosine blocked the apamin
      sensitive AHP of dopaminergic neurons with mean IC(50) values of 152, 15, and 47
      microM, respectively. The benzyl and butyl derivatives were less potent. Methyl
      laudanosine had no effect on the I(h) current, action potential parameters, or
      membrane resistance of dopaminergic cells, or on the decrease in input resistance
      induced by muscimol, indicating a lack of antagonism at GABA(A) receptors.
      Interestingly, 100 microM methyl-laudanosine induced a significant increase in
      spiking frequency of dopaminergic neurons but not of CA1 pyramidal cells,
      suggesting the possibility of regional selectivity. Binding experiments on
      laudanosine derivatives were in good agreement with electrophysiological data.
      Moreover, methyl-laudanosine has no affinity for voltage-gated potassium
      channels, and its affinity for SK channels (IC(50) 4 microM) is superior to its
      affinity for muscarinic (IC(50) 114 microM) and neuronal nicotinic (IC(50) > or
      =367 microM) receptors. Methyl-laudanosine may be a valuable pharmacological tool
      to investigate the role of SK channels in various experimental models.

PMID- 12183679
TI  - (-)U50,488H [(trans)-3,4-dichloro-N-methyl-N-[2-(1-pyrrolidinyl)
      cyclohexyl]benzeneacetamide] induces internalization and down-regulation of the
      human, but not the rat, kappa-opioid receptor: structural basis for the
      differential regulation.
AB  - We showed previously that prolonged activation by (-)U50,488H [(trans)-3,4
      dichloro-N-methyl-N-[2-(1-pyrrolidinyl)-cyclohexyl]benzeneacetamide] led to
      internalization and down-regulation of the human kappa opioid receptor (hkor),
      but not the rat kappa opioid receptor (rkor). Herein, we investigated structural
      determinants in the receptors underlying these differences using chimeric and
      mutant receptor constructs epitope tagged with FLAG and stably expressed in
      Chinese hamster ovary cells (CHO). The FLAG-hkor, but not the FLAG-rkor,
      underwent internalization and down-regulation after exposure to (-)U50,488H.
      Monensin did not have any effect on the intracellular receptor pool of the FLAG
      rkor or rkor with or without (-)U50,488H treatment, indicating that the lack of (
      )U50,488H-induced internalization is not due to rapid resurfacing of the rkor.
      Two chimeric receptors, FLAG-h/rkor and FLAG-r/hkor, were generated, in which the
      C-terminal domains of the hkor and the rkor were switched. The FLAG-r/hkor
      displayed significant (-)U50,488H-induced internalization and down-regulation,
      whereas the FLAG-h/rkor did not, indicating that the C-terminal domain
      contributes to the differences between the rkor and the hkor. To further
      characterize, we generated two mutants, FLAG-hkorS358N and FLAG-rkorN358S in
      which the locus 358 was exchanged. The FLAG-hkorS358N mutant displayed greatly
      reduced (-)U50,488H-induced internalization and no down-regulation compared with
      the FLAG-hkor, indicating that Ser358 in the hkor is critical for these
      processes. However, the FLAG-rkorN358S mutant was internalized, but not down
      regulated, demonstrating that N358 prevents the rkor from being internalized, but
      it may not have a role in the lack of down-regulation of the rkor. In addition,
      the trafficking of the FLAG-rkorN358S mutant seems to be more complex than the
      rkor and the hkor.

PMID- 12183680
TI  - Ethanol suppresses fast potentiation of glycine currents by glutamate.
AB  - Excitatory (glutamate) and inhibitory (GABA(A) and glycine) receptor/channels
      coexist in many neurons. To assess effects of ethanol on the interaction of
      glutamate and glycine receptors, glycine-induced current (I(Gly)) was recorded by
      a whole-cell patch-clamp technique from neurons freshly dissociated from the
      ventral tegmental area of rats. A conditioning prepulse of glutamate (1-3 s, 1
      mM) significantly and reversibly potentiated responses to a pulse of glycine.
      This potentiation was increased when extracellular calcium was raised to 12 mM
      and reduced by including 10 mM 1,2-bis-(2-aminophenoxy)ethane-N,N,N',N'
      tetraacetic acid in the internal recording medium. It was not affected by 5
      microM 1-N,O-bis-(5-isoquinolinesulfonyl)-N-methyl-L-tyrosyl]-4-phenylpiperazine
      (KN-62), a selective inhibitor of calcium/calmodulin-dependent protein kinase II.
      In a concentration-response analysis, a conditioning pulse of glutamate
      significantly lowered the EC(50) for glycine and increased the maximal I(Gly).
      Kinetic analysis of the currents indicated that glutamate slowed deactivation of
      glycine-gated chloride channels; therefore, glutamate may increase the affinity
      of glycine receptors for glycine. When coapplied with glycine, ethanol (10 mM)
      potentiated I(Gly) in 35% of neurons from the ventral tegmental area. In
      contrast, when coapplied with glutamate and glycine, ethanol suppressed the
      glutamate-induced potentiation of I(Gly) in these neurons. This suppression was
      also observed when ethanol and glycine were coapplied after a glutamate prepulse.
      A similar effect was observed when ethanol alone did not potentiate I(Gly). These
      findings suggest that glutamate-induced calcium influx modulates glycine
      receptors by a mechanism that can be blocked by ethanol.

PMID- 12183681
TI  - Acute cocaine differentially alters accumbens and striatal dopamine clearance in
      low and high cocaine locomotor responders: behavioral and electrochemical
      recordings in freely moving rats.
AB  - Behavioral responses of rodents to cocaine are characterized by marked individual
      variability. Here, outbred male Sprague-Dawley rats were profiled based on
      concomitant recording of behavioral and electrochemical responses. Rats were
      categorized as either low or high cocaine responders (LCRs or HCRs, respectively)
      based on their differential locomotor responsiveness to an acute, low-dose
      injection of cocaine (10 mg/kg i.p.). LCRs and HCRs also differed in other
      cocaine-induced behaviors. The role of the dopamine transporter (DAT) in
      mediating the behavioral differences in cocaine responsiveness in LCRs and HCRs
      was investigated by high-speed chronoamperometric recording of exogenous dopamine
      (DA) clearance signals in nucleus accumbens (NAc) and dorsal striatum (dSTR).
      Higher volumes of DA were required in NAc of HCRs, than of LCRs, to produce
      equivalent peak DA signal amplitude (A(max)) responses. In HCRs, systemic cocaine
      administration evoked an immediate and prolonged 2-fold augmentation in A(max) in
      both brain regions, coincident with locomotor activation. The cocaine-induced
      decrease in the efficiency of DA clearance (k) in NAc of HCRs was more immediate
      and prolonged than in dSTR, where the transient decrease coincided with maximal
      stereotypic behavior. In contrast, in LCRs, A(max) was not altered by cocaine,
      and decay rate constant (k) was transiently attenuated only in dSTR. Correlation
      analyses of individual responses revealed that cocaine-induced changes in DA
      clearance signal parameters accounted for 20 to 40% of the variation in
      behavioral responsiveness to cocaine. Overall, our findings emphasize the
      importance of characterizing individual responses to understand more fully the
      range of functional consequences resulting from DAT inhibition.

PMID- 12183682
TI  - Inhibition by naloxone stereoisomers of beta-amyloid peptide (1-42)-induced
      superoxide production in microglia and degeneration of cortical and mesencephalic
      neurons.
AB  - Previously we reported that naloxone stereoisomers, in an opioid receptor
      independent manner, attenuated the inflammation-mediated degeneration of
      dopaminergic neurons by inhibition of the activation of microglia, the resident
      immune cells in the brain. Recently we discovered that beta-amyloid peptide Abeta
      (1-42) exhibited enhanced neurotoxicity toward both cortical and mesencephalic
      neurons through the activation of microglia and production of superoxide. The
      purpose of this study was to determine whether naloxone isomers had any effect on
      Abeta (1-42)-induced neurodegeneration. Pretreatment of either cortical or
      mesencephalic neuron-glia cultures with 1 to 10 microM (-)-naloxone, prior to
      treatment for up to 11 days with 0.1 to 3 microM Abeta (1-42), afforded
      significant neuroprotection as judged by neurotransmitter uptake,
      immunocytochemical analysis, and cell counting. More importantly, (+)-naloxone,
      the ineffective enantiomer of (-)-naloxone in binding opioid receptors, was
      equally effective in affording neuroprotection. Mechanistically, inhibition of
      Abeta (1-42)-induced production of superoxide in microglia underlay the
      neuroprotective effect of naloxone stereoisomers. Moreover, neuroprotection and
      inhibition of Abeta (1-42)-induced superoxide production was also achieved with
      naloxone methiodide, a charged analog with quaternary amine, suggesting that the
      site of action for naloxone isomers is at the cell surface of microglia. These
      results demonstrated that naloxone isomers, through mechanisms unrelated to the
      opioid receptors, were capable of inhibiting Abeta (1-42)-induced microglial
      activation and degeneration of both cortical and mesencephalic neurons. Combined
      with our previous observations with inflammagen-induced neurodegeneration,
      naloxone analogs, especially (+)-naloxone, may have potential therapeutic
      efficacy for the treatment of Alzheimer's and Parkinson's disease.

PMID- 12183683
TI  - Behavioral and neurochemical effects of 5-(4-[4-(5-Cyano-3-indolyl)-butyl)-butyl]
      1-piperazinyl)-benzofuran-2-carboxamide (EMD 68843): a combined selective
      inhibitor of serotonin reuptake and 5-hydroxytryptamine(1A) receptor partial
      agonist.
AB  - 5-(4-[4-(5-Cyano-3-indolyl)-butyl)-butyl]-1-piperazinyl)-benzofuran-2-carboxamide
      (EMD 68843; vilazodone) is a novel compound with combined high affinity and
      selectivity for the 5-hydroxytryptamine (5-HT) transporter and 5-HT(1A)
      receptors. EMD 68843 was tested as a prototype compound, which benefits from dual
      pharmacological effects that could increase extracellular 5-HT to levels higher
      than those produced by conventional selective serotonin reuptake inhibitors
      (SSRIs). In Sf9 cells, EMD 68843 increased guanosine 5'-O-(3
      [(35)S]thiotriphosphate) binding to 69% of the magnitude of the full 5-HT(1A)
      receptor agonist R-(1)-trans-8-hydroxy-2-[N-n-propyl-N-(39-iodo-29-propenyl)]
      aminotetralin (8-OH-PIPAT), indicating that it is a partial agonist at 5-HT(1A)
      receptors. Acute, systemic administration of EMD 68843 produced a larger maximal
      increase of extracellular 5-HT than the SSRI fluoxetine in both the ventral
      hippocampus (HPv) (558 versus 274%) and the frontal cortex (FC) (527 versus
      165%). Regional differences in the response to the two drugs were also observed.
      These effects may be attributed to the differential regulation of 5-HT release in
      the HPv and FC by 5-HT(1A) autoreceptors. When challenged with the 5-HT(1A)
      receptor agonist 8-hydroxy-2-(di-n-propylamino) tetralin (8-OH-DPAT), EMD 68843
      induced increases in extracellular 5-HT were greatly reduced in the HPv but to a
      lesser extent in the FC. In behavioral studies, EMD 68843 produced antidepressant
      like effects in the forced swimming test in both rats and mice but only within a
      narrow dosage range. Like fluoxetine, EMD 68843 did not produce the symptoms of
      the 5-HT behavioral syndrome in rats but, unlike fluoxetine, pretreatment with
      EMD 68843 blocked expression of the 5-HT behavioral syndrome induced by 8-OH
      DPAT. Taken together, the results show that EMD 68843 augments extracellular 5-HT
      levels in forebrain regions to a greater extent than fluoxetine. At higher doses,
      however, weak efficacy of EMD 68843 at postsynaptic 5-HT(1A) receptors may
      inhibit the expression of rodent antidepressant-like behaviors.

PMID- 12183684
TI  - In vitro, pharmacokinetic, and pharmacodynamic interactions of ketoconazole and
      midazolam in the rat.
AB  - Interactions of midazolam and ketoconazole were studied in vivo and in vitro in
      rats. Ketoconazole (total dose of 15 mg/kg intraperitoneally) reduced clearance
      of intravenous midazolam (5 mg/kg) from 79 to 55 ml/min/kg (p < 0.05) and
      clearance of intragastric midazolam (15 mg/kg) from 1051 to 237 ml/min/kg (p <
      0.05), increasing absolute bioavailability from 0.11 to 0.36 (p < 0.05).
      Presystemic extraction occurred mainly across the liver as opposed to the
      gastrointestinal tract mucosa. Midazolam increased electroencephalographic (EEG)
      amplitude in the beta-frequency range. Ketoconazole shifted the concentration-EEG
      effect relationship rightward (increase in EC(50)), probably because ketoconazole
      is a neutral benzodiazepine receptor ligand. Ketoconazole competitively inhibited
      midazolam hydroxylation by rat liver and intestinal microsomes in vitro, with
      nanomolar K(i) values. At a total serum ketoconazole of 2 microg/ml (3.76 microM)
      in vivo, the predicted reduction in clearance of intragastric midazolam by
      ketoconazole (to 6% of control) was slightly greater than the observed reduction
      in vivo (to 15% of control). However, unbound serum ketoconazole greatly
      underpredicted the observed clearance reduction. Although the in vitro and in
      vivo characteristics of midazolam in rats incompletely parallel those in humans,
      the experimental model can be used to assess aspects of drug interactions having
      potential clinical importance.

PMID- 12183685
TI  - Quantitative trait loci affecting initial sensitivity and acute functional
      tolerance to ethanol-induced ataxia and brain cAMP signaling in BXD recombinant
      inbred mice.
AB  - In previous work, we identified genetic correlations between cAMP accumulation in
      the cerebellum and sensitivity to the incoordinating effects of ethanol. A
      genetic correlation suggests that common genes underlie the phenotypes
      investigated. One method for provisionally identifying genes involved in a given
      phenotypic measure is quantitative trait locus (QTL) analysis. Using a panel of
      30 BXD recombinant inbred strains of mice and the progenitors (DBA/2J and
      C57BL/6J), and the dowel test for ataxia, we measured the blood ethanol
      concentrations at the time an animal first fell from the dowel and acute
      functional tolerance (AFT), and investigated cAMP signaling in the cerebellum.
      Cyclic AMP accumulation was measured in whole-cell preparations of cerebellar
      minces from individual mice under basal or stimulated conditions. We conducted a
      genome-wide QTL analysis of the behavioral and biochemical measures with >2000
      genetic markers to identify significant associations. Western blot and
      comparative sequencing analysis were used to compare cAMP response element
      binding protein (CREB) levels and protein-coding sequence, respectively. QTL
      analyses correlating strain means with allelic status at genetic markers
      identified several significant associations (p < 0.01). Analysis of variance
      revealed an effect of strain on behavioral and biochemical measures. There was a
      significant genetic correlation between initial sensitivity and basal cAMP
      accumulation in the cerebellum. We identified 6 provisional QTLs for initial
      sensitivity on four chromosomes, 6 provisional QTLs for AFT on four chromosomes,
      and 11 provisional QTLs for cAMP signaling on nine chromosomes. Two loci were
      found to overlap for measures of initial sensitivity and for cAMP signaling.
      Given the genetic correlation between initial sensitivity and basal cAMP
      accumulation, we investigated candidate genes in a QTL on chromosome 1.
      Comparative sequence analysis was performed, and protein levels were compared
      between C57 and DBA mice for Creb1. No significant differences were detected in
      coding sequence or protein levels for CREB. These results suggest that although
      ethanol sensitivity and cAMP signaling are determined by multiple genes, they may
      share certain genetic codetermination.

PMID- 12183686
TI  - Effects of pyridine ring substitutions on affinity, efficacy, and subtype
      selectivity of neuronal nicotinic receptor agonist epibatidine.
AB  - 2'-Pyridine ring substituted analogs of epibatidine were assessed for equilibrium
      binding affinity, functional potency, and efficacy at rat neuronal nicotinic
      receptors expressed in Xenopus oocytes. Binding affinities were determined in
      membrane homogenates from oocytes expressing alpha2beta2, alpha2beta4,
      alpha3beta2, alpha3beta4, alpha4beta2, or alpha4beta4. Efficacy (relative to
      acetylcholine) and potency were measured electrophysiologically with oocytes
      expressing alpha3beta4, alpha4beta2, and alpha4beta4. Hydroxy, dimethylamino, and
      trifluoromethanesulfonate analogs had affinities too low for accurate
      measurement. The bromo analog had affinities 4- to 55-fold greater at beta2 than
      at beta4-containing receptors, modestly greater efficacy at alpha4beta4 than at
      alpha4beta2, and 5- to 10-fold greater potency at a4beta4 than at alpha3beta4 or
      alpha4beta2. The fluoro analog displayed affinities 52- to 875-fold greater at
      beta2- than at beta4-containing receptors, efficacy at alpha4beta4 receptors 3
      fold greater than at alpha4beta2 and alpha3beta4, and was equipotent at all
      receptors tested. The norchloro analog showed affinities 114- to 3500-fold
      greater at beta2- than at beta4-containing receptors, 2-fold greater efficacy at
      alpha4beta2 and alpha4beta4 than at alpha3beta4, and 4- to 5-fold greater potency
      at alpha4beta4 and alpha3beta4 than at alpha4beta2. The amino analog displayed
      affinities 10- to 115-fold greater at beta2- than at beta4-containing receptors,
      3-fold greater efficacy at alpha3beta4 than at alpha4beta2, and 2- to 4-fold
      greater potency at alpha3beta4 and alpha4beta4 than at alpha4beta2. Although
      these compounds displayed a variety of differences in affinity, efficacy, and
      potency, with one exception (binding affinity and functional potency at
      alpha4beta4 receptors) there were no significant correlations among these
      properties.

PMID- 12183687
TI  - Functional effects of systemically administered agonists and antagonists of mu,
      delta, and kappa opioid receptor subtypes on body temperature in mice.
AB  - We have investigated the roles of peripheral and central mu, delta, and kappa
      opioid receptors and their subtypes in opioid-induced hypothermia in mice.
      Measuring rectal temperature after i.p. injection, opioid agonists [morphine,
      fentanyl, SNC80 ((+)-4-[(alphaR)-alpha-((2S,5R)-4-allyl-2,5-dimethyl-1
      piperazinyl)3-methoybenzyl]-N,N-diethylbenzamide), U50,488H ((trans-(dl)-3,4
      dichloro-N-methyl-N-[2-(1-pyrrolidinyl)cyclohexyl]-benzeneacetamide), and
      loperamide)] were tested alone or with opioid antagonists [naloxone, beta
      funaltrexamine, naloxonazine, naltrindole, 7-benzylidenenaltrexone (BNTX),
      naltriben, nor-binaltorphimine, 2-(3,4-dichlorophenyl)-N-methyl-N-[(1S)-1-(3
      isothiocyanatophenyl)-2-(1-pyrrolidinyl)ethyl]acetamide (DIPPA), and methyl
      naltrexone] given 15 min after the agonist. All agonists produced dose-related
      hypothermia, although at low doses, morphine and U50,488H produced hyperthermia.
      The effects of morphine and fentanyl were antagonized by naloxone and by the
      mu(1) antagonist naloxonazine. The delta(2) antagonist naltriben potentiated the
      hypothermic effect of mu agonists. SNC80-induced hypothermia was blocked by the
      delta antagonist naltrindole but not by the delta(1) antagonist BNTX. Depending
      on the dose, the delta(2) antagonist naltriben produced either a potentiation or
      an attenuation of the effect of SNC80. U50,488H-induced hypothermia was
      antagonized by the kappa antagonist nor-binaltorphimine but not by acute
      treatment with the irreversible kappa antagonist DIPPA. The peripherally acting
      opioid loperamide produced hypothermia that could be blocked by several mu-,
      delta-, or kappa-selective antagonists as well as the peripherally acting
      antagonist methyl-naltrexone. Methyl-naltrexone produced a weak potentiation of
      morphine-, fentanyl-, and U50,488H-induced hypothermia, whereas a significant
      attenuation of SNC80-induced hypothermia was observed. In conclusion, at high
      doses, morphine- and fentanyl-induced hypothermia may involve composite action on
      mu, kappa, and possibly delta opioid receptors after initial activation. In the
      mediation of delta opioid-induced hypothermia, no clear selectivity between the
      delta(1) and delta(2) subtypes was defined. The studies provide new evidence that
      maintenance of the initial effects of agonist/receptor activation vary with the
      agonist and the receptor. The existence of both central and peripheral components
      of opioid-induced hypothermia is also emphasized.

PMID- 12183688
TI  - Brain reward system activity in major depression and comorbid nicotine
      dependence.
AB  - Major depressive disorder (MDD) and nicotine dependence are highly comorbid. MDD
      patients may use nicotine to ameliorate depressive symptoms. The pathophysiology
      of the comorbidity of these two disorders is unknown. We hypothesized that a
      dysfunctional dopaminergic brain reward system (BRS) might be a neurobiological
      link between MDD and nicotine dependence and that smoking modulates the activity
      of the BRS by enhancing dopaminergic activity and relieving some depressive
      symptoms. Eighteen nicotine-dependent, nonmedicated subjects with Diagnostic and
      Statistical Manual of Mental Disorders (4th edition) diagnosis of MDD and 16
      nicotine-dependent, control subjects participated in a double-blind, placebo
      controlled, randomized parallel study. A single 30-mg oral dose of d-amphetamine
      (d-amph) was used to release dopamine and probe the activity of the BRS. The d
      amph-mediated physiological and rewarding effects were assessed at baseline and
      post-treatment using standardized and validated questionnaires. Our results show
      that d-amph significantly increased blood pressure (p < 0.001). Subjective
      rewarding d-amph effects increased in both groups. Negative subjective effects
      were reported while on placebo during nonsmoking sessions. A significant
      correlation between depression severity (Hamilton depression scale) and d-amph
      rewarding effects was found in MDD smoker subjects (Addiction Research Center
      Inventory composite: r = 0.89, p < 0.000; profile of mood states composite: r =
      0.71, p < 0.003; and visual analog scales composite: r = 0.78, p < 0.005). These
      data show that smoking did not modify the response to d-amph in MDD or control
      subjects, but decreased overall negative mood state during placebo sessions.
      Severity of depression was significantly correlated with increased rewarding
      effects of d-amph. Thus, although the BRS may be dysfunctional in MDD subjects,
      chronic nicotine use does not modify response to d-amph.

PMID- 12183689
TI  - Characterization of pharmacological efficacy of VX-148, a new, potent
      immunosuppressive inosine 5'-monophosphate dehydrogenase inhibitor.
AB  - Inosine 5'-monophosphate dehydrogenase (IMPDH) enzyme catalyzes the rate-limiting
      step in the de novo biosynthesis of guanine nucleotides. Proliferation of
      lymphocytes is critically dependent on this de novo nucleotide synthesis pathway.
      Hence, IMPDH is an attractive target for the development of immunosuppressive
      drugs. VX-148 is a novel, uncompetitive IMPDH inhibitor with a K(i) value of 6 nM
      against IMPDH type II enzyme. VX-148 is slightly more potent than mycophenolic
      acid and VX-497 in inhibiting the proliferation of mitogen-stimulated primary
      human lymphocytes (IC(50) value of ~80 nM). The inhibitory activity of VX-148 is
      alleviated in the presence of exogenous guanosine. VX-148 does not inhibit
      proliferation of nonlymphoid cell types such as fibroblasts, indicating
      selectivity for inhibition of IMPDH activity. VX-148 is orally bioavailable in
      rats and mice; oral administration of VX-148 inhibits primary antibody response
      in mice in a dose-dependent manner with an ED(50) value of 38 mg/kg b.i.d. VX-148
      significantly prolongs skin graft survival at 100 mg/kg b.i.d. in mice. These
      results demonstrate that VX-148 is a potent and specific IMPDH inhibitor with a
      favorable pharmacokinetic profile and good pharmacological activity in mice, and
      thus support development of VX-148 as an immunosuppressive drug.

PMID- 12183690
TI  - Genetically engineered analogs of ascomycin for nerve regeneration.
AB  - The polyketides FK506 (tacrolimus) and FK520 (ascomycin) are potent
      immunosuppressants that function by inhibiting calcineurin phosphatase through
      formation of an FKBP12-FK506/520-calcineurin ternary complex. They also have
      calcineurin-independent neuroregenerative properties in cell culture and animal
      models of nervous system disorders. Based on the crystal structure of the FKBP12
      FK506-calcineurin complex, we deduced that the 13- and 15-methoxy groups of FK506
      or FK520 are important for inhibition of calcineurin phosphatase but not for
      binding to FKBP12. By genetic modification of the FK520 gene cluster, we
      generated 13- and 15-desmethoxy analogs of FK520 that contain hydrogen, methyl,
      or ethyl instead of methoxy at one or both of these positions. These analogs bind
      FKBP12 tightly, have decreased calcineurin phosphatase inhibition and
      immunosuppressive properties, and enhance neurite outgrowth in cell cultures. A
      representative compound was also shown to accelerate nerve regeneration and
      functional recovery in the rat sciatic nerve crush model.

PMID- 12183691
TI  - Studies on functional sites of organic cation/carnitine transporter OCTN2
      (SLC22A5) using a Ser467Cys mutant protein.
AB  - The organic cation/carnitine transporter OCTN2 mediates transport of carnitine
      and organic cations in Na(+)-dependent and Na(+)-independent manners,
      respectively. However, the mechanism of molecular recognition of different
      substrates has not been clarified yet. We previously found a single amino acid
      change in OCTN2, Ser467Cys (S467C), in the Japanese population and observed a
      decreased carnitine transport but unchanged organic cation transport compared
      with wild type. Therefore, we conducted detailed kinetic and functional analyses
      of the substrate recognition sites of wild-type and S467C-mutant OCTN2. The K(m)
      value for carnitine of S467C-mutant was increased about 15-fold over that of the
      wild type. Mutual inhibition kinetics of carnitine and tetraethylammonium (TEA)
      were not completely competitive, suggesting that the binding sites are very close
      to each other, but not identical. Several organic anions such as valproate, as
      well as organic cations, significantly inhibited carnitine and TEA uptake by
      OCTN2, and valproate showed Na(+)-dependent inhibition of OCTN2-mediated TEA
      uptake. The Na(+)-activation kinetics of the S467C mutant was similar to that of
      the wild type. Furthermore, a significant decrease of the TEA uptake-inhibitory
      potency of valproate was observed in S467C-mutant OCTN2. These observations
      suggest that the decrease in affinity of S467C-mutant OCTN2 for carnitine was
      caused by functional alteration of the anion (carboxyl moiety of carnitine)
      recognition site located in trans-membrane domain 11, which is closely related to
      the Na(+)-binding site, on OCTN2 protein. These results demonstrate that OCTN2
      has functional sites for carnitine and Na(+) and that the carnitine-binding site
      is involved, in part, in the recognition of organic cations.

PMID- 12183692
TI  - MT(2) melatonin receptors are present and functional in rat caudal artery.
AB  - In rat caudal artery, contraction to melatonin results primarily from activation
      of MT(1) melatonin receptors; however, the role of MT(2) melatonin receptors in
      vascular responses is controversial. We examined and compared the expression and
      function of MT(2) receptors with that of MT(1) receptors in male rat caudal
      artery. MT(1) and MT(2) melatonin receptor mRNA was amplified by reverse
      transcription-polymerase chain reaction from caudal arteries of three rat strains
      (i.e., Fisher, Sprague-Dawley, and Wistar). Antisense (but not sense) (33)P
      labeled oligonucleotide probes specific for MT(1) or MT(2) receptor mRNA
      hybridized to smooth muscle, as well as intimal and adventitial layers, of caudal
      artery. In male Fisher rat caudal artery denuded of endothelium, melatonin was 10
      times more potent than 6-chloromelatonin to potentiate contraction to
      phenylephrine, suggesting activation of smooth muscle MT(1) melatonin receptors.
      The MT(1)/MT(2) competitive melatonin receptor antagonist luzindole (3 microM),
      blocked melatonin-mediated contraction (0.1-100 nM) with an affinity constant
      (K(B) value of 157 nM) similar to that for the human MT(1) receptor. However, at
      melatonin concentrations above 100 nM, luzindole potentiated the contractile
      response, suggesting blockade of MT(2) receptors mediating vasorelaxation and/or
      an inverse agonist effect at MT(1) constitutively active receptors. The
      involvement of MT(2) receptors in vasorelaxation is supported by the finding that
      the competitive antagonists 4-phenyl 2-acetamidotetraline and 4-phenyl-2
      propionamidotetraline, at MT(2)-selective concentrations (10 nM), significantly
      enhanced contractile responses to all melatonin concentrations tested (0.1 nM-10
      microM). We conclude that MT(2) melatonin receptors expressed in vascular smooth
      muscle mediate vasodilation in contrast to vascular MT(1) receptors mediating
      vasoconstriction.

PMID- 12183693
TI  - Developing skilled performance of lumbar spine manipulation.
AB  - OBJECTIVE: To quantify elements of spinal manipulation therapy performance and to
      test the strategy of combined rehearsal and quantitative feedback as a means of
      enhancing student skill development. DESIGN: Randomized, controlled study.
      SETTING: Chiropractic college. SUBJECTS: Thirty-nine chiropractic student
      volunteers entering the manipulation technique training course participated after
      providing informed consent. METHODS: Student performance of lumbar spinal
      manipulation therapy was quantified at the beginning, middle, and end of a
      trimester with a manipulation table imbedded with an AMTI force plate. Loads
      acting passing through the L5/S1 functional spinal unit were estimated by inverse
      dynamics. Participating students rehearsed the mamillary push, diversified
      procedure following either the standard curriculum alone or a modified curriculum
      adding a training aid as assigned on a randomized basis. Student's t and chi(2)
      tests were used to explore and describe biomechanical parameter changes over time
      as the semester progressed. RESULTS: Significant changes in performance between
      the standard curriculum and modified curriculum were observed in several
      biomechanical parameters. CONCLUSION: The reported project used a rehearsal
      program defined empirically and was self-administered in practice by the student.
      Results demonstrated significant changes in performance of spinal manipulation by
      students using the training aid instrument versus those who did not. With
      quantitative training aids and biomechanical measurement systems, future training
      programs may be optimized and tested.

PMID- 12183694
TI  - Forces applied during manual therapy to patients with low back pain.
AB  - BACKGROUND: To date, there is little information available regarding the forces
      used during mobilization treatment of patients with low back pain (LBP).
      OBJECTIVE: This study measured such forces and investigated whether the force
      characteristics could be predicted on the basis of physical therapist and patient
      characteristics. SUBJECTS: Ten physical therapists applied a central
      posteroanterior (PA) mobilization treatment to 80 patients with LBP, providing
      data on treatment of 123 lumbar levels. METHODS: Physical therapists were
      required to treat their patients while the patients lay on an instrumented couch.
      This couch has been shown to be highly accurate in its measurement of force in 3
      directions (error <2%) and has demonstrated high test-retest reliability (ICC [2,
      1], 99% CI = 0.99-1.00). The forces applied by the physical therapists were
      recorded over a 10-second period. Data on the characteristics of the physical
      therapists and patients were collected by means of questionnaires. RESULTS: The
      force used by physical therapists related not only to patient characteristics but
      also to physical therapist characteristics. Interestingly, current pain intensity
      and nature of symptoms did not affect the forces used. The overall patterns of
      the force characteristics were generally consistent with previous studies
      performed in asymptomatic subjects. However, the magnitude of the force applied
      and the frequency of each grade used in the present study are relatively higher
      than in earlier studies. CONCLUSION: These preliminary data provide some useful
      quantitative information about the forces used during mobilization treatment of
      patients with LBP. Also, the force characteristics described here may provide
      useful data for both teaching and research in manual therapy.

PMID- 12183695
TI  - Vertebral arteries and cervical rotation: modeling and magnetic resonance
      angiography studies.
AB  - OBJECTIVE: To determine whether lumen narrowing in vertebral arteries during
      atlanto-axial rotation is due to stretch or localized compression. DESIGN AND
      SETTING: Experiments with models were made in a private chiropractic clinic,
      whereas studies of cadaveric specimens were performed in an anatomy laboratory.
      Doppler ultrasound and magnetic resonance angiography (MRA) studies were carried
      out in the radiology department of a public hospital. PATIENTS: Eight patients
      had their vertebral arteries examined by use of a Doppler velocimeter and MRA.
      MAIN OUTCOME MEASURE: Stenosis of the vertebral arteries caused by stretch,
      localized compression, or kinking. RESULTS: All 16 vertebral arteries from the 8
      patients displayed no changes in their lumen dimensions with full cervical
      rotation, although curves in each of the arteries did change. The model and
      cadaveric vertebral arteries demonstrated localized compression or kinking of the
      vessel wall with atlanto-axial rotation contralaterally but revealed no evidence
      of major contribution of stretching to stenosis. CONCLUSION: The lumen of
      vertebral arteries is usually unaffected by atlanto-axial rotation. In cases
      where there is stenosis, this is mainly due to localized compression or kinking.
      These findings are relevant to premanipulative screening of vertebral arteries
      with Doppler ultrasound scanning.

PMID- 12183696
TI  - The effect of talocrural joint manipulation on range of motion at the ankle.
AB  - OBJECTIVE: To determine whether a single high-velocity, low-amplitude thrust
      manipulation to the talocrural joint altered ankle range of motion. DESIGN: A
      randomized, controlled and blinded study. SUBJECTS: Asymptomatic male and female
      volunteers (N = 41). METHODS: Subjects were randomly assigned into either an
      experimental group (n = 20) or a control group (n = 21). Both ankles of subjects
      in the experimental group were manipulated by using a single high-velocity, low
      amplitude thrust to the talocrural joint. Pretest and posttest measurements of
      passive dorsiflexion range of motion were taken. RESULTS: No significant changes
      in dorsiflexion range of motion were detected between manipulated ankles and
      those of control subjects. A significantly greater pretest dorsiflexion range of
      motion existed in those ankles in which manipulation produced an audible
      cavitation. CONCLUSION: Manipulation of the ankle does not increase dorsiflexion
      range of motion in asymptomatic subjects. Ankles that displayed a greater pretest
      range of dorsiflexion were more likely to cavitate, raising the possibility that
      ligament laxity may be associated with the tendency for ankles to cavitate.

PMID- 12183697
TI  - Evaluation of axial and flexural stresses in the vertebral body cortex and
      trabecular bone in lordosis and two sagittal cervical translation configurations
      with an elliptical shell model.
AB  - BACKGROUND: Osteoarthritis and spinal degeneration are factors in neck and back
      pain. Calculations of stress in clinically occurring configurations of the
      sagittal cervical spine are rare. OBJECTIVE: To calculate and compare combined
      axial and flexural stresses in lordosis versus cervical configurations in
      anterior and vertical sagittal head translated positions. DESIGN: Digitized
      measurements from lateral cervical radiographs of 3 different shapes were used to
      calculate axial loads and bending moments on the vertebral bodies of C2-C7.
      METHODS: An elliptical shell model was used to model horizontal cross-sections of
      the vertebral bodies of C2 through T1. Axial and flexural stresses were
      calculated with short compression block equations. Elliptical shell modeling
      permitted separation of stresses into cortical and inner medullary regions.
      Digitized radiographic points were used to create polynomials representing the
      shape of the sagittal cervical curvatures from C1 to T1. To calculate bending
      moments at each vertebral segment, moment arms from a vertical line through C1
      were determined from digitizing. RESULTS: Compared with the normal lordosis,
      stresses on the anterior vertebral body cortical margins of C5-T1 in the sagittal
      translated postures are compression rather than tension. At the posterior
      vertebral bodies in the anteriorly translated position and vertically translated
      postures, the stresses change from compression to tension at C5 through T1. In
      absolute value (ABS) compared with values at the same segments in a normal
      lordosis, the magnitude of the combined anterior stresses in the sagittal
      postures are higher at C5-C7 (eg, ABS[sigma(straight)/sigma(normal)]
      approximately 1.25 to 4.25). CONCLUSIONS: Vertebral body stresses are reversed in
      direction at C5-T1 in sagittal translated postures compared to a normal lordosis.
      Stress analysis, with implications for bone remodeling, indicates that both
      sagittal head translation postures, anterior head carriage, and vertical head
      translation, are undesirable configurations in the cervical spine.

PMID- 12183698
TI  - Guidelines for the diagnosis of osteoporosis by densitometric methods.
AB  - BACKGROUND: Osteoporosis is a major health hazard for postmenopausal women and
      elderly people. Local, national, and international organizations developed
      clinical practice guidelines for the diagnosis and management of osteoporosis and
      the prevention of osteoporotic fractures. Low bone mineral density (BMD) is the
      most important risk factor for fragility fractures. Bone densitometry is the best
      method to measure BMD in an individual. Many risk factors contribute to the
      development of osteoporosis and increase the fracture risk independently from
      BMD. Guidelines must be comprehensive, factual, simple to implement, and should
      provide the clinician, patients, governments, and payers with the best evidence
      available. OBJECTIVES: The objectives of this article were to review national and
      international guidelines to establish a congruent set of parameters that may aid
      the clinician in the decision-making process for the diagnosis of osteoporosis.
      DATA SOURCES: An online search of several databases provided 18 guidelines for
      this review. Comparison among the guidelines was made on 10 different aspects:
      format, focus, significance of hip and vertebral body fractures, primary
      diagnostic considerations, BMD measurement technology, interpretation, reporting
      and follow-up, equipment reliability and quality control, risk factors
      considered, and methodologic quality of the guidelines. Tables were created for
      easier comparison on the aspects covered and supported by each guideline.
      RESULTS: None of the guidelines reviewed fulfills all the requirements of good
      clinical practice guidelines. CONCLUSIONS: Further works should finally provide
      all those interested with a more complete and thorough set of guidelines based on
      the best evidence available.

PMID- 12183699
TI  - Neuropathic osteoarthropathy in the diabetic foot.
AB  - OBJECTIVE: To discuss a case involving a 55-year-old diabetic woman with
      neuropathic osteoarthropathy initiated by a fall. CLINICAL FEATURES: The patient
      fell into a hole, injuring her left foot. Because of the anesthesia associated
      with her diabetic peripheral neuropathy, she did not notice the ensuing plantar
      puncture wound. The patient assumed that her swelling was a result of a sprain.
      Mild dislocation and osseous fragmentation was noted within the midfoot on
      radiographs. The neuropathic osteoarthropathy progressed until the patient was
      later casted. Plain films taken at the time of cast removal demonstrated
      resorption and consolidation of fragmentation, but the dislocation was unaltered.
      INTERVENTION AND OUTCOME: The patient was scheduled for surgery and wound
      debridement. However, before surgery, complications of a burn sustained on the
      contralateral foot required fifth ray amputation. Surgery of the left foot has
      been postponed until adequate postsurgical healing has occurred at the right foot
      amputation site. CONCLUSION: This article provides tools for the timely diagnosis
      and treatment of neuropathic osteoarthropathy. An increased understanding of this
      entity will help lead to a reduction in the incidence of delayed treatment
      resulting from misdiagnosis.

PMID- 12183700
TI  - Evaluating the quality of clinical practice guidelines.

PMID- 12183701
TI  - The Webster Technique: a chiropractic technique with obstetric implications.
AB  - OBJECTIVE: To survey members of the International Chiropractic Pediatric
      Association (ICPA); regarding the use of the Webster Technique for managing the
      musculoskeletal causes of intrauterine constraint, which may necessitate cesarean
      section. METHODS: Surveys were mailed to 1047 US and Canadian members of the
      ICPA. RESULTS: One hundred eighty-seven surveys were returned from 1047 ICPA
      members, constituting a return rate of 17.86%. Seventy-five responses did not
      meet the study inclusion criteria and were excluded; 112 surveys (11%) provided
      the data. Of these 112 surveys, 102 (92%) resulted in resolution of the breech
      presentation, while 10 (9%) remained unresolved. CONCLUSION: The surveyed doctors
      reported a high rate of success (82%) in relieving the musculoskeletal causes of
      intrauterine constraint using the Webster Technique. Although the sample size was
      small, the results suggest that it may be beneficial to perform the Webster
      Technique in month 8 of pregnancy, when breech presentation is unlikely to
      spontaneously convert to cephalic presentation and when external cephalic version
      is not an effective technique. When successful, the Webster Technique avoids the
      costs and/or risks of external cephalic version, cesarean section, or vaginal
      trial of breech.In view of these findings, the Webster Technique deserves serious
      consideration in the health care management of expectant mothers exhibiting
      adverse fetal presentation.

PMID- 12183702
TI  - Perinatal outreach education--the role of academic medical centers.

PMID- 12183703
TI  - Paying for children to participate in research: a slippery slope or an
      enlightened stairway?

PMID- 12183704
TI  - Shiga toxin-producing E coli: two tests are better than one.

PMID- 12183705
TI  - Essential fatty acid deficiency and nutritional supplementation in cystic
      fibrosis.

PMID- 12183706
TI  - The aging of the cardiovascular system: when should children be treated like
      adults?

PMID- 12183707
TI  - Pediatric end-stage renal disease: heart as a target.

PMID- 12183708
TI  - Shwachman-Diamond syndrome.

PMID- 12183709
TI  - The ethics of paying for children's participation in research.

PMID- 12183710
TI  - Shiga toxin-producing Escherichia coli in children with diarrhea: a prospective
      point-of-care study.
AB  - OBJECTIVE: To conduct a prospective cohort study to determine the frequency and
      characteristics of Shiga toxin (Stx)-producing Escherichia coli (STEC) infections
      in children with diarrhea attending an emergency department and a private clinic
      in Seattle, Washington. METHODS: Between November 1998 and October 2001, 1851
      stools were processed for STEC by sorbitol-MacConkey (SMAC) agar screening and a
      commercial Stx enzyme immunoassay (EIA). RESULTS: STEC belonging to serotypes
      O157:H7 (n = 28), O103:H2 (n = 4), O118:H16 (n = 2), O26:H11, O111:nonmotile,
      O111:H8, O121:H19, and O rough:H11 (n = 1 each) were recovered from 39 (2.1%)
      stools. EIA and SMAC agar detected 89% and 100% of the patients with E coli
      O157:H7, respectively. E coli O157:H7-infected patients had significantly higher
      frequencies of bloody stools, fecal leukocytes, and abdominal tenderness and
      shorter symptom duration. Hemolytic uremic syndrome developed in 5 (18%) and none
      of the children infected with E coli O157:H7 and non-O157:H7 STEC, respectively
      (P =.30). CONCLUSIONS: E coli O157:H7 is the predominant STEC in this population.
      Children infected with E coli O157:H7 have clinical presentations different from
      those whose stools contain non-O157:H7 STEC. Culture and Stx detection are needed
      to optimally detect STEC of all serotypes in stools. SMAC agar screening should
      not be replaced by EIA.

PMID- 12183711
TI  - Effect of an organized lipid matrix on lipid absorption and clinical outcomes in
      patients with cystic fibrosis.
AB  - OBJECTIVES: To compare the absorption of a lysophosphatidylcholine,
      monoglyceride, and fatty acid matrix (organized lipid matrix, OLM) with that of a
      triacylglycerol (TG)-based fat meal in patients with cystic fibrosis (CF). STUDY
      DESIGN: Five adolescents with CF and 3 control patients were given fat meals
      supplemented with retinyl palmitate of either OLM or TG at a 2-week interval. In
      a clinical trial, 73 patients with CF were randomly assigned to nutritional
      supplements containing either OLM or TG for a 1-year double-blind trial followed
      by a 6-month observation period. RESULTS: The peak increases and areas under the
      curve for TG and retinyl palmitate after the fat meal were 10-fold higher after
      OLM than after the TG fat load and did not differ from values obtained in control
      patients. OLM led to better clinical outcomes in terms of energy intake from the
      diet, weight-for-age Z score, essential fatty acid status, vitamin E, and retinol
      binding protein. Height-for-age Z score and FEV(1) only reached statistical
      significance at the end of the 6-month observation period. CONCLUSIONS: These
      results suggest that OLM is a readily absorbable source of fat and energy in CF
      and is an effective nutritional supplement.

PMID- 12183712
TI  - Left atrial size in children with hypertension: the influence of obesity, blood
      pressure, and left ventricular mass.
AB  - OBJECTIVE: To evaluate the prevalence of left atrial enlargement and the
      correlates of left atrial size in children and adolescents with essential
      hypertension. BACKGROUND: Left atrial enlargement has been associated with
      increased risk of cardiovascular disease, including stroke in adults. Risk
      factors for left atrial size in adults with hypertension include age, race, and
      obesity. METHODS AND RESULTS: Patients (n =112; average age, 14.2 years) with
      essential hypertension were studied with echocardiography. The average left
      atrial dimension was 2.8 (+/- 0.5) cm; 51% patients had left atrial dimension
      >95% upper confidence limit. The patients with left atrial enlargement had
      greater body mass index (P <.05) than those without left atrial enlargement. In
      multiple regression analysis, height, body mass index, systolic blood pressure,
      and left ventricular geometry were significant independent correlates of left
      atrial size. Children with eccentric left ventricular hypertrophy were more
      likely to have a larger left atrial dimension. CONCLUSIONS: Left atrial
      enlargement is prevalent in children and adolescents with essential hypertension.
      This may indicate an increased risk of cardiovascular disease morbidity and
      mortality. Control of obesity and blood pressure elevation offer two approaches
      for treatment that may prevent left atrial enlargement.

PMID- 12183713
TI  - Cardiovascular mortality in children and young adults with end-stage kidney
      disease.
AB  - OBJECTIVE: To analyze cardiovascular death in a national end-stage renal disease
      (ESRD) population. STUDY DESIGN: This retrospective, observational study with
      data from the US Renal Data Systems analyzed 1380 deaths from 1990 to 1996 among
      patients who started ESRD therapy as children and died before 30 years of age.
      RESULTS: Percentage of cardiac deaths (n = 311) varied by age and was higher
      among black patients (0-4 years, 36%; 5-9 years, 18%; 10-14 years, 35%; 15-19
      years, 22%; 20-30 years, 32%) than white patients (18%, 12%, 17%, 14%, and 23%,
      respectively). Among black patients, cardiac deaths occurred in 11% of transplant
      recipients, 34% of dialysis patients, and among white patients 9% and 25%,
      respectively. Black patients were 1.6 times more likely to die of a cardiac death
      (P <.001) than white patients. Transplant recipients had 78% lower risk of
      cardiac death than dialysis patients (odds ratio = 0.22; P =.0001). The cardiac
      death rate among dialysis patients was 21.4 per 1000 patient-years in black
      patients compared with 20.5 in white patients. Transplantation cardiac death
      rates were lower in black patients, 2.1 per 1000 patient-years, and 1.3 in white
      patients. CONCLUSIONS: Cardiovascular death accounts for 23% of pediatric and
      young adult ESRD deaths. Black patients and dialysis patients are at higher risk
      of a cardiac death compared with white patients and transplant recipients.
      Further studies are needed to identify risk factors associated with
      cardiovascular death in patients with ESRD.

PMID- 12183714
TI  - Chronic recurrent multifocal osteomyelitis: clinical outcomes after more than
      five years of follow-up.
AB  - OBJECTIVE: To determine the clinical outcomes of children with chronic recurrent
      multifocal osteomyelitis (CRMO). STUDY DESIGN: Inception cohorts of children with
      CRMO were established at two tertiary pediatric centers. Outcome data were
      obtained through review of hospital charts, interview and examination of
      patients, and completion of questionnaires by patients. RESULTS: Of 45 eligible
      subjects, 23 (51%) were assessed. Median time since diagnosis was 13 years
      (range, 6-25). At evaluation, 6 (26%) had active disease; 18 (78%) had Health
      Assessment Questionnaire scores of 0 (no/minimal physical disability), and 5 had
      scores >0. Some impairment was seen in all domains of measurement of quality-of
      life test, especially those concerning nonphysical aspects of health. Six (26%)
      subjects continued to have pain as a result of CRMO. Associated medical problems
      included arthritis in 6, sacroiliitis in 3, psoriasis in 5, recurrent pustular
      rashes in 2, and inflammatory bowel disease in 3. CONCLUSIONS: Long-term clinical
      outcomes for children with CRMO appear to be generally good, with most subjects
      having no evidence of disease activity or sequelae. However, a number of subjects
      had persistent disease and, therefore, remain at risk of physical and psychologic
      complications. Further research is required to identify patients at risk for
      persistent disease, and to determine therapies that may prevent morbidity.

PMID- 12183715
TI  - Altered bone mineral density and body composition, and increased fracture risk in
      childhood acute lymphoblastic leukemia.
AB  - OBJECTIVE: To evaluate fracture rate and bone mineral density (BMD) and body
      composition in children with acute lymphoblastic leukemia (ALL) treated with
      dexamethasone-based chemotherapy. STUDY DESIGN: Children with ALL (n = 61)
      participated. At diagnosis, during therapy, and one year after cessation of
      therapy, BMD and body composition were measured using dual energy X-ray
      absorptiometry of lumbar spine (LS) and total body (TB). Serum markers of bone
      turnover were assessed. RESULTS: BMD(LS) was significantly reduced at diagnosis,
      and remained low during therapy. BMD(TB) was normal at diagnosis, with a fast
      decrease in the first 32 weeks, in which chemotherapy was relatively intensive.
      Apparent ("volumetric") BMD(LS) was also reduced, but this did not reach
      significance at diagnosis and follow-up. Bone formation markers were reduced at
      diagnosis; formation as well as resorption markers increased during treatment.
      Fracture rate was 6 times higher in ALL patients compared with healthy controls.
      Lean body mass was decreased at baseline. Percentage of body fat increased
      significantly during therapy. After ALL treatment was completed, BMD and body
      composition tended to improve. CONCLUSIONS: Children with ALL are at risk for
      osteopenia because of the disease itself and the intensive chemotherapy. Fracture
      rate increases substantially, not only during but also shortly after treatment.

PMID- 12183716
TI  - A prospective study of bone mass and body composition in female adolescent
      gymnasts.
AB  - OBJECTIVE: To examine changes in bone and body composition of adolescent female
      artistic gymnasts (GYM; n = 7), level 5+, compared with nongymnast controls (CON;
      n = 10) over 3 years. STUDY DESIGN: Areal bone mineral density (aBMD; g/cm(2)),
      bone mineral content (BMC; g) and bone area (cm(2)), of the total body (TB),
      total proximal femur (TPF), trochanter (Tr), femoral neck, lumbar spine (LS), and
      distal radius were measured using dual-energy X-ray absorptiometry. Fat-free soft
      tissue mass (FFST; g), fat mass (g), and percent body fat (%FAT) were also
      assessed. RESULTS: No initial differences in height or weight between GYM and CON
      were observed, and both groups demonstrated parallel increases in these
      parameters over time (P <.05; h(2) >or=0.15). At baseline, GYM possessed
      significantly lower %FAT and higher aBMD at all sites (except TB; P <.05; h(2)
      >or=0.15). Over 3 years, GYM increased more than CON (P <.05; eta (2) >or=0.15)
      in TB, Tr, and TPF aBMD, TB and LS BMC, and FFST. CONCLUSION: Female adolescents
      participating in competitive artistic gymnastics training over 3 years have
      enhanced rates of aBMD, BMC and FFST accrual.

PMID- 12183717
TI  - A population-based study on the incidence and possible pre- and perinatal
      etiologic risk factors of biliary atresia.
AB  - OBJECTIVE: To study the incidence, etiologic risk factors, and outcome of biliary
      atresia. STUDY DESIGN: Register study using Swedish national health databases.
      The study population consisted of 1,204,791 children, corresponding to 99% of the
      entire cohort of Swedish children born between 1987 and 1997, with an end point
      of follow-up at 2 years of age. Cases with biliary atresia with and without major
      heart malformations were identified with indicators from various national health
      databases. RESULTS: Eighty-five cases with biliary atresia were identified, the
      incidence being 1 in 14,000. A major heart malformation was found in 13 (15%)
      cases. In a multivariate analysis, 4 independent risk factors were identified:
      high maternal age (odds ratio [OR] = 3.0), parity of at least 4 (OR = 2.2),
      prematurity (OR = 2.9), and low birth weight for gestational age (OR = 4.7). No
      significant differences were found in the distribution of birth months. The
      outcome did not differ between the two groups with and without major heart
      malformations, nor with respect to any of the risk factors. CONCLUSIONS: The
      Swedish incidence of biliary atresia is similar to that found in other European
      countries. The identified risk factors may suggest the existence of a maternal
      vulnerability and the importance of viral infections transmitted from mother to
      fetus/neonate.

PMID- 12183718
TI  - Self-assessment of sexual maturity status in children with Crohn's disease.
AB  - OBJECTIVE: To evaluate the validity of self-assessment of sexual maturity status
      (SMS) in children with Crohn's disease (CD), a pediatric chronic disease that
      often affects growth and development. STUDY DESIGN: Self-assessment of SMS in 100
      children (34 girls) ages 8 to 18 years with CD from the Children's Hospital of
      Philadelphia was compared with an independent assessment by one well trained
      pediatrician, using drawings and written descriptions of Tanner stages of breast,
      genital, and pubic hair development. RESULTS: Overall, subjects with CD (age,
      14.3 +/- 2.8 years) had delayed growth status based on height-for-age (HAZ) and
      weight-for-age Z scores (WAZ). Boys were more growth delayed (HAZ, -0.90 +/- 1.1;
      WAZ, -0.75 +/- 1.3) than girls (HAZ, -0.45 +/- 1.3; WAZ, -0.20 +/- 1.1). Kappa
      coefficients (kappa) showed excellent agreement between child and physician
      assessment of SMS, ranging from kappa = 0.74 to 0.85, depending on sex and SMS
      component, corresponding to a 79% to 88% agreement. When not in agreement,
      children tended to overestimate their SMS. Boys who overestimated (n = 8) had
      significantly higher weight and BMI status than boys who assessed accurately.
      CONCLUSIONS: Self-assessment of SMS was a reliable and valid method in children
      with CD and is useful in screening for maturational delay in children with
      chronic disease.

PMID- 12183719
TI  - Oral stimulation accelerates the transition from tube to oral feeding in preterm
      infants.
AB  - OBJECTIVE: To assess whether an oral stimulation program, before the introduction
      of oral feeding, enhances the oral feeding performance of preterm infants born
      between 26 and 29 weeks' gestational age. STUDY DESIGN: Preterm infants (n = 32)
      were randomized into an experimental and control group. Infants in the
      experimental group received an oral stimulation program consisting of stimulation
      of the oral structures for 15 minutes. Infants in the control group received a
      sham stimulation program. Both were administered once per day for 10 consecutive
      days, 48 hours after discontinuation of nasal continuous positive air pressure.
      RESULTS: Independent oral feeding was attained significantly earlier in the
      experimental group than the control group, 11 +/- 4 days (mean +/- SD) versus 18
      +/- 7 days, respectively (P =.005). Overall intake and rate of milk transfer were
      significantly greater over time in the experimental group than the control group
      (P =.0002 and.046, respectively). There was no difference in length of hospital
      stay between the 2 groups. CONCLUSION: An early oral stimulation program
      accelerates the transition to full oral feedings in preterm infants. This was
      associated with greater overall intake and rate of milk transfer observed in the
      experimental group when compared with the control group.

PMID- 12183720
TI  - Tauroursodeoxycholic acid (TUDCA) in the prevention of total parenteral nutrition
      associated liver disease.
AB  - OBJECTIVE: To determine whether tauroursodeoxycholic acid (TUDCA) would prevent
      or ameliorate the liver injury in neonates treated with total parenteral
      nutrition (TPN). STUDY DESIGN: Eligible infants were enrolled after surgery when
      serum direct bilirubin (DB) was <2 mg/dL. TUDCA (30 mg/kg/day) was given
      enterally to 22 subjects. A concurrent untreated/placebo group was evaluated for
      comparison (n = 30). Blood chemistries including alanine aminotransferase (ALT),
      alkaline phosphatase (AP), conjugated bilirubin (CB), and bile acids (BA) were
      obtained weekly. RESULTS: There was no difference in peak serum CB, ALT, AP, or
      BA levels between the TUDCA-treated and control infants. When stratified for
      birth weight (<1500 g and >1500 g), no differences in peak CB, ALT, AP, or BA
      were noted. Serum CB levels were similar between TUDCA-treated and control
      infants after 14, 40, 60, 70, and 120 days of TPN. CONCLUSION: TUDCA appears
      ineffective in preventing the development or treatment of TPN-associated
      cholestasis in neonates. Erratic biliary enrichment and prolonged inability to
      initiate treatment may compromise the utility of enterically administered TUDCA
      for TPN-treated infants.

PMID- 12183721
TI  - Protein insufficiency and linear growth restriction in phenylketonuria.
AB  - OBJECTIVES: To study the role of protein sufficiency, age, calorie sufficiency,
      and phenylalanine levels in children with phenylketonuria (PKU) and determine how
      these affect linear growth. METHODS: Age, growth measures, plasma prealbumin, and
      mean phenylalanine levels were analyzed from a chart review of 38 children with
      early and continuously treated PKU. RESULTS: A regression model was calculated
      investigating the effects of prealbumin, age, body mass index, and mean
      phenylalanine level on height. In this model, plasma prealbumin of <20 was
      associated with a loss of 45 height percentiles, whereas age and body mass index
      also had smaller but statistically significant effects. Prealbumin was correlated
      with height and age such that children with lower prealbumin levels were shorter
      and younger. There was no significant correlation between age and height or mean
      plasma phenylalanine level and height. A prealbumin level of 20 mg/dL appeared to
      constitute a threshold level, below which height growth was very significantly
      impaired. CONCLUSIONS: There is a strong relation between protein insufficiency,
      as determined by plasma prealbumin levels, and linear growth impairment. We
      suggest that a plasma prealbumin level of at least 20 mg/dL is necessary for
      optimal growth in children with PKU.

PMID- 12183722
TI  - Indicators of adult height outcome in classical 21-hydroxylase deficiency
      congenital adrenal hyperplasia.
AB  - OBJECTIVE: To obtain objective information on the relationship between adult
      height (AH), glucocorticoid (GC) dose, and degree of hormonal suppression in a
      population of patients with 21-hydroxylase deficiency congenital adrenal
      hyperplasia (21-OHD CAH) to optimize treatment regimes. STUDY DESIGN: Multicenter
      retrospective chart review of patients with salt wasting 21-OHD CAH diagnosed in
      the first 6 months of life, and who had reached AH (n = 54). The data were
      compiled into a single database. RESULTS: Mean adult height standard deviation
      score - midparental height standard deviation score was -1.1 for both sexes.
      Growth velocity was normal during childhood but compromised during infancy and
      puberty. Onset and tempo of puberty were normal-to-delayed. Bone age was closely
      correlated with chronologic age (r = 0.93). AH was negatively correlated with
      androstenedione in infancy (r -0.68; P =.03) and childhood (-0.66; P <.01) and
      with testosterone in childhood (r -0.44; P =.01), but not with
      dehydroepiandrosterone or 17-hydroxyprogesterone. GC dose was not associated with
      AH. CONCLUSIONS: Mean AH was in the lower range of genetic potential in this
      group of persons with 21-OHD CAH. Androgen levels should be used in conjunction
      with growth velocity measurements to optimize GC dosing in persons with 21-OHD
      CAH.

PMID- 12183723
TI  - Idiopathic thrombocytopenic purpura diagnosed during the second decade of life.
AB  - OBJECTIVE: To retrospectively review our institutional experience of adolescents
      with idiopathic thrombocytopenic purpura (ITP). STUDY DESIGN: Medical record
      review of all patients diagnosed with ITP between the ages of 10 and 18 years
      seen at our center from January 1976 to March 2000. RESULTS: Data were collected
      from 126 patients. Of the evaluable 110 cases, 63 (57%) satisfied the criteria
      for chronic ITP, 30 (27%) for acute ITP, and 17 (15%) were uncertain. Sex
      distribution and mean ages were similar in all 3 groups. Platelet count at
      presentation was higher in patients with chronic ITP. Splenectomy was performed
      in 24 patients, with 17 (77%) of 22 having normal platelet counts at last follow
      up. Outcome for the nonsplenectomized patients with chronic ITP included
      normalization of platelet count (n = 4), minimal or no bleeding without treatment
      (n = 29), treatment for ongoing symptoms (n = 5), and unknown (n = 1). Two
      patients died, 1 from intracranial hemorrhage and 1 from Escherichia coli sepsis
      and pulmonary hemorrhage. CONCLUSIONS: Patients 10 to 18 years of age with ITP
      are more likely than younger children to have chronic disease. Many patients with
      ITP recover without drug therapy or need for splenectomy. ITP in adolescents
      shares features of both childhood and adult ITP.

PMID- 12183724
TI  - Serum pancreatic enzymes define the pancreatic phenotype in patients with
      Shwachman-Diamond syndrome.
AB  - OBJECTIVE: To evaluate the role of serum enzymes for defining the pancreatic
      phenotype in Shwachman-Diamond syndrome (SDS), an inherited multisystem
      condition. STUDY DESIGN: Serum pancreatic trypsinogen and isoamylase were
      measured in 164 patients known or presumed to have SDS. The diagnosis was
      confirmed in 90 patients. Among 74 unconfirmed cases, 35 ("probable SDS") had
      hematologic dysfunction but lacked documented pancreatic dysfunction, whereas 39
      patients ("improbable SDS") lacked both documented pancreatic and hematologic
      dysfunction. Classification and regression tree (CART) analysis was performed in
      90 patients with SDS and 134 control patients to establish a rule for defining
      the pancreatic phenotype of SDS; the rule was then applied to the patients with
      unconfirmed diagnosis. RESULTS: In the control patients, serum trypsinogen showed
      little variation with age, whereas serum isoamylase values rose from birth on,
      attaining adult values by 3 years. For patients with SDS, serum trypsinogen
      values were low in young patients and tended to increase with age, whereas serum
      isoamylase values remained low at all ages. The CART rule combined results from
      both enzymes and classified the pancreatic phenotype in all but one SDS patient,
      who was <3 years of age. Excluding patients <3 years of age, CART identified the
      pancreatic phenotype in 82% and 7% of the "probable SDS" and "improbable SDS"
      cases, respectively. CONCLUSIONS: Serum pancreatic enzymes are useful for
      determining the pancreatic phenotype and confirming the diagnosis of SDS.

PMID- 12183725
TI  - Shwachman-Diamond syndrome: report from an international conference.

PMID- 12183726
TI  - Allergy to extensively hydrolyzed cow's milk proteins in infants: safety and
      duration of amino acid-based formula.
AB  - Infants (n = 52) allergic to cow's milk protein and extensively hydrolyzed
      formulas received an amino acid-based formula. The amino acid-based formula
      proved to be safe, with infants exhibiting an overall gain in length and weight.
      Children with allergy restricted to extensively hydrolyzed formulas were
      diagnosed earlier and tolerated cow's milk protein earlier than children with
      multiple food allergy.

PMID- 12183727
TI  - Polyhydramnios: a predictor of severe growth impairment in achondroplasia.
AB  - The phenotypical characteristics in 20 children with achondroplasia were examined
      in relation to the occurrence of polyhydramnios. A history of polyhydramnios (9
      of 20 cases) was associated with a lower height (SD) (P <.05), more severe
      shortening of the lower segment and upper limbs (P =.0001), and higher frequency
      of left-handedness (P =.0081).

PMID- 12183728
TI  - Influence of nasogastric tubes on gastroesophageal reflux in preterm infants: a
      multiple intraluminal impedance study.
AB  - To investigate whether a nasogastric tube predisposes to gastroesophageal reflux,
      16 preterm infants underwent 48-hour recordings of multiple intraluminal
      impedance with the catheter tip in the lower esophagus or stomach for 24 hours
      each. There were 72 (range, 40-145) reflux episodes with the esophageal placement
      and 122 (range, 60-147) during the gastric position (P <.01).

PMID- 12183729
TI  - Recurrent necrobiosis lipoidica diabeticorum associated with venous insufficiency
      in an adolescent with poorly controlled type 2 diabetes mellitus.
AB  - Type 2 diabetes mellitus and associated long-term complications have become a
      significant health problem in adolescents. We report a 16-year-old girl with
      poorly controlled type 2 diabetes mellitus who had recurrent necrobiosis
      lipoidica diabeticorum associated with venous insufficiency.

PMID- 12183730
TI  - Mechanism of sudden cardiac arrest while swimming in a child with the prolonged
      QT syndrome.
AB  - We describe the abrupt sequence of events resulting in cardiac arrest while
      swimming in a 12-year-old with long QT syndrome. Diving into cold water resulted
      in an irregular cardiac rhythm and further prolongation of the QT interval,
      followed by a premature ventricular complex, which initiated pulseless
      ventricular tachycardia (rate >300/minute). The transition from sinus rhythm to
      ventricular tachycardia occurred in <5 seconds and was followed by a successful
      implantable cardioverter-defibrillator rescue shock.

PMID- 12183731
TI  - Methemoglobinemia in an infant receiving nitric oxide after the use of eutectic
      mixture of local anesthetic.
AB  - High levels of methemoglobinemia can cause tissue hypoxia and cyanosis. We report
      the case of a 7-month-old girl with pulmonary dysplasia receiving inhaled nitric
      oxide who had cyanosis caused by methemoglobinemia after prolonged use of a
      eutectic mixture of local anesthetics cream.

PMID- 12183733
TI  - Semitransparent meningocele at the occipital region.

PMID- 12183732
TI  - Prevention of otitis media: role of pneumococcal conjugate vaccines in reducing
      incidence and antibiotic resistance.

PMID- 12183734
TI  - Biliary atresia, the Kasai operation, and the chance of success.

PMID- 12183735
TI  - Employing the nasal potential difference as a diagnostic test for cystic fibrosis
      in neonates: potential pitfalls.

PMID- 12183736
TI  - Optimizing immunization--going beyond parent reminders.

PMID- 12183737
TI  - Doxapram and neurodevelopmental outcome.

PMID- 12183738
TI  - Thyroid disease in children with 22q11.2 deletion syndrome.

PMID- 12183739
TI  - Erythromycin in ELBW infants.

PMID- 12183741
TI  - The horse on the dining room table.

PMID- 12183740
TI  - Intake and output.

PMID- 12183742
TI  - Improving oral health care for the frail elderly: a review of widespread problems
      and best practices.
AB  - Oral health is an important component of overall health, well-being, and quality
      of life for institutionalized elders. Despite reports by nurses of the importance
      of oral hygiene, empirical evidence shows that daily oral care interventions have
      not been effective in safeguarding the oral and general health of this vulnerable
      population. Effective practice must involve not only recognizing its importance
      but also ensuring that daily oral hygiene receives the same priority as other
      care practices.

PMID- 12183744
TI  - Postoperative complications and the older adult.

PMID- 12183743
TI  - Improving CNA education with a game show.
AB  - Providing continuing education for certified nursing assistants (CNAs) to meet
      mandatory requirements is challenging. It does not matter which state or region
      you work in or how large or small your facility, educators face the same
      challenges. The traditional lecture seems ineffective in the new millennium. This
      article presents an entertaining and engaging avenue for learning in a format
      tailored after the television game show Who Wants to be a Millionaire? to create
      an interdisciplinary approach involving all staff.

PMID- 12183745
TI  - Family caregivers' preferences in caring for their hospitalized elderly
      relatives.
AB  - We know little about family preferences in participating in hospital care for
      elders. This pilot study was conducted to explore the kind of care actions that
      family caregivers prefer to do for their hospitalized elderly relatives. The
      instrument used was a 14-item questionnaire based on a qualitative study
      conducted by the author. The results indicated that 95% of these family
      caregivers (n = 40) would prefer to participate in 10 or more types of family
      care actions. The implications for nursing practice are discussed. Future
      research will focus on identifying factors influencing family preferences, the
      relationship between the preferences and actual performance, and how nurses can
      help family caregivers participate in the care they desire.

PMID- 12183746
TI  - Can a beverage cart help improve hydration?
AB  - The purpose of this study was to determine the effectiveness of a hydration
      program to improve hydration and prevent conditions associated with dehydration
      (delirium, urinary tract infections, respiratory infections, falls, skin
      breakdown, and constipation). Data showed a significant increase in fluid in each
      body compartment, significant decrease in the number of laxatives, increase in
      the number of bowel movements, decline in the number of falls, and decrease in
      cost during the hydration period.

PMID- 12183747
TI  - Care modes for the older adult with gastroesophageal reflux disease.
AB  - Gastroesophageal reflux disease is a common chronic disease in the older
      population. Because of the cumulative effects of acid reflux and delayed gastric
      emptying, the older adult is at risk for such complications as peptic strictures,
      esophagitis, and Barrett's esophagus. Providing information on the current care
      modes (lifestyle, dietary, pharmacologic, and surgical interventions) will help
      identify relevant solutions and help the older adult generate alternative safe
      and effective solutions to manage the disease. Many people struggle to change
      their lives and may need assistance to break old habits.

PMID- 12183748
TI  - Career ladders: an important element in CNA retention. Certificate nursing
      assistant.
AB  - In August 1999, a consortium of individuals joined to develop and evaluate a
      career ladder for certified nursing assistants in Boston. The consortium
      consisted of representatives from Benjamin Health Care Center, Massachusetts
      Extended Care Federation, and Boston Private Industry Council. Funded by a
      Department of Labor grant, the project was implemented to evaluate the effects on
      turnover and retention when opportunities for career development are provided.
      The population first studied was a group of men and women interested in ending
      their dependence on the welfare system and seeking full-time employment in long
      term care. As part of the project, the curriculum was first piloted at Benjamin
      Health Care Center and tested in 10 long-term care centers across Massachusetts.
      A curriculum evaluation demonstrates positive outcomes.

PMID- 12183750
TI  - Predicting malnutrition in nursing home residents using the minimum data set.
AB  - This article describes the prevalence of protein/calorie malnutrition among newly
      admitted elderly nursing home residents and identifies the most significant
      predictors using Minimum Data Set (MDS) variables. This random selection, cross
      sectional study included 266 residents, 65 and older, from three nursing homes.
      Malnutrition risk factors, indicators, and prevalence variables in the MDS were
      measured for each resident on admission to the nursing home. MDS data provide an
      opportunity for early identification of residents at risk for malnutrition and
      accompanying morbidity. Treating residents who are malnourished or at high risk
      for weight loss on admission could dramatically improve their quality of life.

PMID- 12183751
TI  - The best gifts of all.

PMID- 12183752
TI  - Helping older adults reduce the cost of the drugs they need.

PMID- 12183753
TI  - Cold flashes.

PMID- 12183755
TI  - A research review of the current treatments for radiation-induced oral mucositis
      in patients with head and neck cancer.
AB  - PURPOSE/OBJECTIVES: To review the research studies on the current treatments for
      radiation therapy-(RT-) induced mucositis in patients with head and neck cancer.
      DATA SOURCES: MEDLINE search of the literature from 1966-2001. DATA SYNTHESIS:
      Four types of agents (i.e., antimicrobial, coating, anti-inflammatory, and
      cytokine-like agents) have been evaluated for the management of RT-induced oral
      mucositis in patients with head and neck cancer. Most of the published studies
      had relatively small sample sizes and used inconsistent measures to evaluate the
      extent and severity of oral mucositis. Therefore, definitive conclusions
      regarding the effectiveness of any of the agents tested in the prevention and
      treatment of RT-induced oral mucositis cannot be drawn. CONCLUSIONS: Oral
      mucositis remains the most common complication among patients with head and neck
      cancer. Although a number of strategies and products are being investigated and
      new directions are promising, the therapies tested to date have not produced
      consistent results. IMPLICATIONS FOR NURSING: The most effective measure to treat
      RT-induced mucositis in patients with head and neck cancer is frequent oral
      rinsing with a bland mouthwash, such as saline or a sodium bicarbonate rinse, to
      reduce the amount of oral microbial flora. Dental care, consistent oral
      assessments, and the initiation of a standardized oral hygiene protocol before
      the initiation of cancer treatment are the most effective approaches for oral
      mucositis.

PMID- 12183754
TI  - More than a sore mouth: patients' experience of oral mucositis.
AB  - PURPOSE/OBJECTIVES: To explore patients' experience of chemotherapy-induced oral
      mucositis. DESIGN: Interpretive descriptive, phenomenologic. SETTING: The cancer
      center of a metropolitan teaching hospital in South Australia. SAMPLE: A
      purposive sample of six participants undergoing intensive cytotoxic therapy
      associated with autologous hematopoietic stem cell transplantation. METHODS:
      Patients were interviewed at different stages of their treatment trajectory and
      asked to relate their experience of oral mucositis as it developed and resolved.
      FINDINGS: Participants' reports indicated three distinct phases representing
      linear time in the course of their mucositis: the preparatory phase, the peak
      phase, and the persisting phase. Five themes further abstracted were the presence
      of nurses, therapeutic interventions, manifestations of mucositis, the distress
      of eating (and not eating), and whether the treatment was worthwhile.
      CONCLUSIONS: Oral mucositis is much more than a sore mouth. The effects of
      mucositis are widespread and can have a marked effect on patients' psychological
      well-being. IMPLICATIONS FOR NURSING: Care centers often focus on pain control
      through pharmacologic intervention and overlook the effects of other sequelae.
      Nurses' role in helping patients to cope with mucositis should encompass more
      than providing pharmacologic pain relief.

PMID- 12183756
TI  - The effect of an educational intervention on promoting breast self-examination in
      older African American and Caucasian women.
AB  - PURPOSE/OBJECTIVES: To test the efficacy of innovative, age- and race-sensitive,
      self-monitored, video breast health kits in increasing knowledge about breast
      cancer risk and screening and breast self-examination (BSE) proficiency. DESIGN:
      Quasi-experimental pretest and post-test design. SETTING: Dual-site study in
      community-based settings in the Northeast and Southeast United States. SAMPLE:
      328 women (206 in the intervention group, 122 in the control group) aged 60 or
      older; predominantly African American (77%); mean education of 10.8 years; annual
      income below $10,000 (50%). METHODS: Individual pretest and post-test interviews
      conducted by nurses at two-week intervals assessed knowledge about breast cancer
      risk and screening and BSE proficiency as demonstrated on vested breast models.
      Intervention subjects used video breast health kits in ethnic editions designed
      for the study. Control subjects received educational pamphlets. MAIN RESEARCH
      VARIABLES: Dependent variables were knowledge about breast health and BSE
      proficiency measured by demonstration of inspection and palpation skills and
      detection of lumps in a simulation model. FINDINGS: Three multiple analyses of
      covariance revealed statistically significant differences in outcome variables
      between the intervention and control groups. CONCLUSIONS: The intervention was
      effective in increasing knowledge about breast cancer risk and screening and BSE
      proficiency in this sample of older women. IMPLICATIONS FOR NURSING: These and
      other educational interventions designed specifically for age and race
      sensitivity may enhance cancer screening with vulnerable populations. Future
      studies with more diverse multicultural groups are needed to improve
      understanding of how to best influence breast health behaviors of older women.

PMID- 12183757
TI  - A nurse's primer on recruiting participants for clinical trials.
AB  - PURPOSE/OBJECTIVES: To identify common barriers to the recruitment of
      participants for oncology clinical trials, identify strategies that would be
      useful in increasing enrollment of participants in oncology clinical trials, and
      describe the role of the clinical trial nurse in the recruitment process. DATA
      SOURCES: Published articles and abstracts, empirical studies, conference
      proceedings, references from bibliographies of pertinent articles and books, and
      computerized databases from 1994-2001. DATA SYNTHESIS: The barriers to
      participant recruitment in clinical trials may be categorized as being related to
      either the patient, healthcare provider, or protocol. CONCLUSIONS: Several
      achievable strategies for improving recruitment to oncology clinical trials
      exist. Nurses need to understand the complex and diverse factors that influence
      participant accrual to oncology clinical trials. Strategies to increase
      enrollment should focus on increased communications and education for patients
      and healthcare providers. Dedicated clinical trials nurses can play an integral
      part in the recruitment and accrual of patients to oncology clinical trials.
      IMPLICATIONS FOR NURSING: Clinical trial nurses play many important roles in the
      conduct of oncology clinical trials. To better plan and manage these
      investigations, nurses need to develop strategies to mitigate the complex and
      diverse factors that may influence accrual patterns.

PMID- 12183758
TI  - Relationship of perception of radon as a health risk and willingness to engage in
      radon testing and mitigation.
AB  - PURPOSE/OBJECTIVES: To gather data on radon levels and determine correlations
      among subjects' characteristics, willingness to test for radon, and perceptions
      of radon as a health risk. DESIGN: Descriptive correlational. SETTING: Rural
      DeKalb County in northern Illinois. SAMPLE: 473 respondents from a group of 1,620
      randomly selected county residences. METHODS: Participants were surveyed via
      telephone using the Community Radon Program questionnaire. Radon measurements
      were taken with home radon test kits. MAIN RESEARCH VARIABLES: Gender, income,
      age, educational level, smoking status, race, home ownership, willingness to test
      for radon, and radon risk perception. FINDINGS: Most participants were familiar
      with radon but did not view it as an immediate health hazard and would not have
      screened for radon on their own. 88% of the radon measurements exceeded the U.S.
      Environmental Protection Agency's moderate risk potential level, and 53% exceeded
      the action level (i.e., 4 pCi/L). CONCLUSIONS: Perception of radon as a health
      risk was correlated positively with planning to conduct further radon testing and
      to employ radon mitigation methods. More research is needed on people's
      willingness to obtain radon emission levels and the cancer rates in areas that
      have high potential for radon. IMPLICATIONS FOR NURSING: According to the
      environmental literature, the effect of household radon emissions on the
      development of lung cancer is as great a health risk as secondhand smoke.
      Virtually no nursing literature on the subject has been published. As the primary
      source of health information in many rural counties, nurses, especially public
      health nurses, are at the forefront in public health educational efforts. Nurses
      are the most likely healthcare professionals to enter patients' homes and can
      play a significant role in disseminating information about radon as a potential
      carcinogen.

PMID- 12183759
TI  - Contextual variables, emotional state, and current and expected quality of life
      in breast cancer survivors.
AB  - PURPOSE/OBJECTIVES: To determine the relationship between contextual variables,
      emotional state, and quality of life (QOL) now and expectations for the future in
      survivors of breast cancer. DESIGN: Descriptive and nonexperimental. SETTING AND
      SAMPLE: 148 volunteers and women with breast cancer involved in a program by the
      American Cancer Society. Most subjects were middle-aged (mean = 52.4, SD =
      11.56), were married (72%), and had graduated high school (38%). Time since
      diagnosis was 0.3-19 years (mean = 3.54, SD = 3.61); 74% were diagnosed more than
      five years ago, 54% were not receiving any treatment, and 66% had localized
      breast cancer. METHODS: At home, participants completed a self-report survey for
      personal and contextual variables, Positive and Negative Affect Scale, QOL
      Measurement, and Global Life Satisfaction Scale. MAIN RESEARCH VARIABLES: Time
      since diagnosis, extent of cancer, emotional state, QOL, and global life
      satisfaction. FINDINGS: Women had high positive affect (mean = 37.96) and low
      negative affect (mean = 17.13). QOL and life satisfaction were high. Time since
      diagnosis and extent of disease were related weakly to negative affect and QOL (p
      < 0.001). Positive and negative affect were related moderately to QOL and life
      satisfaction (p < 0.001). Current personal life satisfaction was significantly
      greater than breast cancer survivors' estimates for "most people," and survivors
      expected life satisfaction to increase significantly in five years (p < 0.001).
      Significant differences in QOL were found between those who were diagnosed
      recently and those who were diagnosed 10 or more years previously. CONCLUSIONS:
      Despite breast cancer, women have positive affect, good QOL, and life
      satisfaction. Contextual variables were related weakly to outcomes; emotions were
      related more strongly to outcomes. Survivors were more satisfied with life than
      they estimated others to be and expected satisfaction to increase in the future.
      IMPLICATIONS FOR NURSING: Nurses may use these findings to encourage patients who
      are newly diagnosed with breast cancer. Women with breast cancer adapt well
      despite potential negative outcomes, and survivors even report better QOL than
      they estimate for most people.

PMID- 12183760
TI  - Comparisons between cancer survivors and family members on meaning of the illness
      and family quality of life.
AB  - PURPOSE/OBJECTIVES: To explore the meaning of the illness to the family and
      family quality of life (QOL) for survivors and family members and to describe
      similarities and differences between survivors' and family members' meaning of
      the illness and family QOL. RESEARCH APPROACH: Descriptive, qualitative. SETTING:
      Homes of survivors and family members in an urban metropolitan area in the
      midwestern United States. PARTICIPANTS: A sample of 123 Caucasian and African
      American cancer survivors, one to six years after treatment had ended, and their
      family members (N = 246). Four cancer diagnoses (i.e., breast, colon, prostate,
      and uterine) were represented. METHODOLOGIC APPROACH: Two open-ended questions
      derived from a family model of survivorship. Content analysis was used to analyze
      the responses. MAIN RESEARCH VARIABLES: Meaning of the illness and family QOL.
      FINDINGS: The positive dimensions of survivorship in meaning of the illness and
      family QOL were seen for patients and family members, although long-term
      stressors also were reported. More similarities than differences in meaning and
      QOL were noted between survivors and family members. CONCLUSIONS: Patients' and
      family members' perspectives of the meaning of the illness and family QOL are
      important to assess during survivorship to address both individual- and family
      level perspectives in cancer care. IMPLICATIONS FOR NURSING: Nurses should offer
      opportunities for patients and family members to search for positive meaning in
      the cancer illness, develop strategies to handle stressors that are present
      during survivorship, and enhance family strengths and resources to promote family
      QOL.

PMID- 12183761
TI  - Quality of life after esophagectomy for cancer.
AB  - PURPOSE/OBJECTIVES: To examine symptoms and quality of life (QOL) of
      esophagectomy patients after curative surgery. DESIGN: Longitudinal, descriptive
      pilot study. SETTING: Comprehensive cancer center in the northeastern United
      States. SAMPLE: 23 patients were surveyed: 20 men and 3 women. The mean age was
      62.3 years. METHODS: The European Organization for Research and Treatment of
      Cancer Quality of Life Questionnaire-C30 (version 2.0) and the esophageal
      specific module were used. Data collection included three or four time points:
      before neoadjuvant treatment (if administered), before surgery, and three and six
      months after surgery. MAIN RESEARCH VARIABLES: The effects on symptoms and QOL of
      curative esophagectomy performed by a thoracic surgical oncologist. FINDINGS:
      Global QOL declined slightly over time; this change was not statistically
      significant. A significant inverse relationship was found between symptom
      intensity and global QOL. The intensity of hoarseness, reflux, and diarrhea
      increased significantly pre- to postsurgery. The average symptom intensity for
      the esophageal-specific subset of 24 symptoms increased significantly over time;
      the greatest intensity was found before surgery. CONCLUSIONS: Over the six-month
      observation period, the study found little average change in global QOL or
      functional status. However, symptoms increased significantly during this time
      period. Increased symptoms were associated with decreased QOL. IMPLICATIONS FOR
      NURSING: Symptom management should focus on symptoms that interfere with
      patients' QOL. Further research should target the evaluation of specific
      interventions for symptoms.

PMID- 12183762
TI  - Interferon-induced fatigue in patients with melanoma: a pilot study of exercise
      and methylphenidate.
AB  - PURPOSE/OBJECTIVES: To examine the effect of exercise and methylphenidate on
      fatigue, functional ability, and cognitive function in patients with melanoma.
      DESIGN: Pilot study with comparison to historic controls. SETTING: University
      based cancer center. SAMPLE: 12 patients with melanoma entered and completed the
      study. The mean age was 44 years. METHOD: Eligible patients were recruited before
      their first dose of interferon-a (IFN-a). Patients were instructed to take 20 mg
      sustained-release methylphenidate every morning and follow an aerobic exercise
      program four days a week for 15-30 minutes. Measures included a 12-minute walk,
      the Schwartz Cancer Fatigue Scale, Trail Maker Forms A and B, Medical Outcomes
      Study 36 Short Form, body weight, and daily logs. Fatigue scores were compared to
      usual care historical controls with melanoma receiving only IFN-a. MAIN RESEARCH
      VARIABLES: Fatigue, functional ability, and cognitive function. FINDINGS: 66%
      adhered to exercise and methylphenidate; all adhered to exercise. Fatigue was
      lower for the exercise and methylphenidate group than historic controls.
      Functional ability increased 6% for all patients and 9% for the exercise and
      methylphenidate group. Cognitive function was stable for the exercise and
      methylphenidate group. The exercise-only group showed marked cognitive slowing.
      CONCLUSION: The combination of aerobic exercise and methylphenidate may have a
      positive effect on fatigue, cognitive function, and functional ability. A larger
      sample size and randomized trial is needed to more rigorously evaluate the
      results of exercise and methylphenidate alone or in combination. IMPLICATIONS FOR
      NURSING: Although further study is needed, a combination of exercise and
      methylphenidate may be a practical intervention for patients receiving IFN-a for
      melanoma.

PMID- 12183763
TI  - Transjugular intrahepatic portosystemic shunt in the treatment of portal
      hypertension using memotherm stents: a prospective multicenter study.
AB  - PURPOSE: In a prospective multicenter study, efficacy and safety of transjugular
      intrahepatic portosystemic shunts (TIPS) were evaluated in the treatment of the
      complications of portal hypertension using a new self-expanding mesh-wire stent
      (Memotherm). METHODS: One hundred and eighty-one patients suffering from variceal
      bleeding (either acute or recurrent) or refractory ascites were enrolled.
      Postinterventional follow-up lasted for 8.4 months on average. Differences were
      analyzed by the log-rank test (chi-square) or Wilcoxon test. RESULTS: Shunt
      insertion was completed successfully in all patients (n = 181 patients, 100%).
      During follow-up, shunt occlusion was evident in 23 patients, and shunt stenosis
      was found in 33 patients (12.7% and 18.2%, respectively). Variceal rebleeding
      occurred in 20 of 139 patients (14.4%), with at least one episode of bleeding
      before TIPS treatment. The overall mortality rate of the patients treated by TIPS
      was 39.8%. In 51.4% of these cases (37 of 72 patients), however, the patients
      died within 30 days after TIPS placement. Analysis of subgroups showed that
      patients who underwent emergency TIPS for acute variceal bleeding had a
      significantly higher early mortality compared with other patient groups (p =
      0.0014). CONCLUSION: In the present prospective multicenter study, we were able
      to show that insertion of Memotherm stents is an effective tool for TIPS. The
      occlusion rates seem to be comparable to those reported for the Palmaz stent. It
      could be shown that in particular, those patients who were treated for acute
      bleeding were at high risk of early mortality. Consequently, in such a critical
      condition, the indication for TIPS has to be set carefully.

PMID- 12183764
TI  - The amino bisphosphonate ibandronate prevents calciphylaxis in the rat at doses
      that inhibit bone resorption.
AB  - The present experiments were carried out to test the hypothesis that there is a
      common underlying biochemical mechanism that accounts for the different kinds of
      soft tissue calcification observed in animals that are treated with toxic doses
      of vitamin D. In previous studies we showed that lethal doses of vitamin D cause
      extensive calcification of arteries, lungs, kidneys, and cartilage, and that
      doses of the amino bisphosphonate ibandronate that inhibit bone resorption
      completely inhibit each of these soft tissue calcifications and prevent death. In
      the present experiments we have examined the effect of ibandronate on an entirely
      different type of calcification, the calciphylaxis induced by administration of a
      challenger to rats previously treated with sub-lethal doses of vitamin D. These
      studies show that ibandronate doses that inhibit bone resorption completely
      inhibit artery calcification as well as, in the same rat, the calciphylactic
      responses to either subcutaneous injection of 300 mg FeCl3 or intrascapular
      epilation. Since the vitamin D-treated animals had dramatically increased levels
      of bone resorption, and concurrent treatment with ibandronate normalized
      resorption, these results support the hypothesis that soft tissue calcifications
      in the vitamin D-treated rat may be linked to bone resorption. The ability of
      ibandronate to inhibit all vitamin D-associated calcifications in the rat cannot
      be explained by an effect of ibandronate on serum calcium, since serum calcium
      remained 30% above control levels in the vitamin D-treated animals that also
      received ibandronate.

PMID- 12183765
TI  - Mutational and polymorphic analysis of the estradiol receptor-alpha gene in men
      with symptomatic vertebral fractures.
AB  - In view of the importance of estrogens in the maintenance of the skeleton in men,
      we have carried out mutational analysis of all the exons of the estrogen-receptor
      alpha (ER-alpha) gene in 64 men (36 patients with symptomatic vertebral crush
      fractures and 28 control subjects). Initial screening of the ER-alpha gene,
      carried out by single-strand conformation polymorphism analysis followed by
      sequencing, showed conservative mutations in exon 4 which resulted in a single
      base substitutions producing GGG-->GGC transition in codon 274. We also carried
      out polymorphic analysis of the ER-alpha gene at the PvuII restriction site in 82
      men with a range of bone density measurements (53 with symptomatic vertebral
      fractures and 29 controls). The frequencies of PP, Pp, and pp genotypes were
      20.7%, 48.8%, and 30.5%, respectively. The distribution of the alleles was
      similar in the patients with symptomatic vertebral crush fractures and male
      control subjects. There was no association between ER-alpha genotypes and bone
      mineral density or arthropometric parameters. This relatively small study
      suggests that mutations in the ER-alpha gene are unlikely to be a common cause of
      osteoporosis in men with vertebral fractures. Furthermore, polymorphic variation
      of the ER-alpha gene appears to have little effect on the pathogenesis of
      osteoporosis in men.

PMID- 12183766
TI  - The effect of temporal stimulus characteristics in maintenance of the acoustic
      reflex.
AB  - In normal listeners, acoustic reflex decay (ARD) typically occurs for high- but
      not for low-frequency tones. In patients with acoustic neuromas, decay can be
      obtained at all frequencies, presumably due to poor neural synchrony. These
      observations have led us to hypothesize that resistance to decay is due to robust
      encoding of temporal fine structure of the eliciting stimulus. For a 4-kHz
      stimulus, ARD is reduced by sinusoidal amplitude modulation (SAM), a result
      attributed to the low-frequency pattern of SAM providing the temporal
      characteristics necessary to maintain the reflex. If this interpretation is
      correct, then further reductions in ARD should be seen for stimuli having
      temporal characteristics that even more closely resemble the neural response to
      low-frequency stimulus fine structure. On the other hand, if other perceptual
      qualities of a SAM tone are responsible for the effect (e.g., rate pitch), then
      manipulations of perceived sound quality, rather than temporal characteristics
      per se, should produce similar effects. The experiment reported here included a
      reference condition, (1) 5-kHz pure tone, and three "temporal" manipulations,
      composed of a 5-kHz tone multiplied by (2) a raised 100-Hz sinusoid, (3) a noise
      sample, lowpass filtered at 100 Hz, and (4) a half-wave rectified 100-Hz
      sinusoid. Additional conditions manipulated perceived pitch. These stimuli
      spanned 4.5-8 kHz, including a reference condition, (5) Gaussian noise, and a
      stimulus associated with a 100-Hz pitch, (6) iterated rippled noise. Results show
      the greatest reductions in ARD with the half-wave rectified stimulus, thought to
      most closely mimic the temporal characteristics of a low-frequency tone. Little
      or no reduction in ARD was associated with the iterated rippled noise, suggesting
      that perceived pitch does not play an important role in maintaining the acoustic
      reflex.

PMID- 12183767
TI  - Inhibition has little effect on response latencies in the inferior colliculus.
AB  - The inferior colliculi of all mammals are characterized by a wide range of first
      spike response latencies that can greatly exceed the minimum time required for
      the transmission of input through the lower brainstem. The mechanisms that
      account for long response latencies of up to 50 ms are unclear, but one
      hypothesis is that an early inhibition plays a role in shaping latency. To test
      this hypothesis, response latencies were measured in the inferior colliculi of
      the pallid and mustached bats before and during the blockade of GABAa and glycine
      receptors. The effect of blocking inhibition on response latency was compared
      under stimulus conditions that produced the shortest latency in the predrug
      condition. Multibarrel "piggyback" electrodes were used to iontophoretically
      apply bicuculline and strychnine sequentially while recording from single
      neurons. Predrug latencies ranged from 9 to 26 ms in the pallid bat and from 4 to
      17 ms in the mustached bat. Despite large increases in response magnitude and
      response duration following disinhibition, the blockade of inhibitory receptors
      had modest effects on response latency. In the pallid bat, blocking GABA
      receptors produced latency changes that ranged from -3.8 to +0.2 ms, while
      blocking glycine receptors produced changes from -0.1 to +1.7 ms. Similarly, in
      the mustached bat, blocking GABA receptors caused changes ranging from -10.3 to
      +1.4 ms; blocking glycine receptors in the mustached bat caused changes from -3.6
      to +1.0 ms. The large change of -10.3 ms was an exception. In both species, the
      majority of neurons showed changes of <1 ms. We conclude that a fast, early
      inhibitory input does not appear to play a significant role in shaping the wide
      range of response latencies present in the inferior colliculi of mustached and
      pallid bats.

PMID- 12183768
TI  - Fate of the ectatic infrarenal aorta: expansion rates and outcomes.
AB  - The natural history of the ectatic infrarenal aorta remains undetermined. While
      surveillance protocols have been proposed for true aneurysms, no recommendations
      are currently available for ectatic aortas. The purpose of this study is to
      define the natural history and recommend surveillance protocols for the
      infrarenal aorta 2.5-2.9 cm in diameter. Screening of 12,500 yielded 223 patients
      with an infrarenal abdominal aorta 2.5-2.9 cm in diameter at a university
      affiliated VA medical center. All patients were prospectively followed by
      ultrasound from August 1993 through October 2000 and expansion rates were
      calculated by comparing the first and last study. Multivariate analysis of risk
      factors classically associated with abdominal aortic aneurysm was performed.
      Current data suggest that ectatic infrarenal aortas expand slowly, do not
      rupture, and rarely meet criteria for operative repair. No risk factors linked to
      the development of aneurysms were identified. On the basis of this study we
      recommend that patients with ectatic aortas have a repeat ultrasound 5 years
      after the initial study.

PMID- 12183769
TI  - Synergism between radiotherapy and vascular risk factors in the accelerated
      development of atherosclerosis: a report of three cases.
AB  - Radiotherapy is commonly used in the management of testicular tumors. However, to
      date the risk of radiation-induced vascular occlusive disease in men following
      radiotherapy for testicular cancer has not been regarded as a major factor in
      their long-term care. Several animal studies have shown the importance of
      established vascular risk factors such as hypercholesterolemia and hypertension
      in the pathogenesis of radiation-induced atherosclerosis. This report presents
      three cases of premature chronic iliofemoral arterial disease presenting 5,13,
      and 16 years following exposure to therapeutic irradiation for the treatment of
      testicular cancer. The patients were in the age group of 40-45 years and all
      demonstrated associated known atherosclerotic risk factors. The patients had
      received radiotherapy in the dose of 3,500-4,000 rads in a standard "dog-leg"
      fashion to the ipsilateral aortoiliac lymphatic chain. Our results showed that
      young men treated with radiotherapy for testicular cancer may be targeted from
      the outset for atherosclerotic risk factor reduction to minimize the risk of
      development of late chronic occlusive arterial disease. It may be that a cohort
      of men so treated with historical regimes of radiotherapy and now entering middle
      age should be screened for arterial disease and risk factor reduction.

PMID- 12183770
TI  - Thoracoabdominal aortic aneurysm repair: a prospective cohort study of 121 cases.
AB  - Between October 1990 and June 2001, 121 patients underwent surgery for
      thoracoabdominal aortic aneurysm (TAAA)-99 procedures were elective and 22 were
      for ruptured aneurysms. Between October 1990 and September 1997, the clamp-and-go
      technique was used for all aneurysms (43 patients), and from October 1997, clamp
      and-go was reserved for type IV TAAAs, and atriofemoral bypass (AFB) was used for
      types I, II, and III (78 patients). Overall hospital mortality was 21.4% (26/121)
      12% for the elective group and 64% for the ruptured group. Hospital mortality was
      associated with age (67 years in survivors vs. 73 years in nonsurvivors, p =
      0.03), FEV1<2 L (RR 4.1, p = 0.01), CSF drainage (RR 5.0, p = 0.03), type II
      aneurysms vs. other aneurysms (RR 3.7, p = 0.02), and relative inexperience (mean
      rank in the series was 52 in survivors vs. 30 in nonsurvivors, p = 0.01). The
      overall incidence of neurologic deficits due to spinal cord ischemia was 6.2%
      (paraplegia in 4.4%). Temporary dialysis was necessary in 13% of patients, and
      chronic dialysis in 2%. In long-term follow-up of patients undergoing elective
      repair, 5-year survival was 80% and median survival was 7.9 years. Mortality and
      neurologic deficits have improved over time as a consequence of either increased
      surgical experience, the adoption of a protocolized strategy for repair, or
      secular improvements in ICU care. Long-term survival after elective TAAA repair
      is excellent.

PMID- 12183771
TI  - Recurrent transient ischemic attacks as the initial presenting manifestation of
      type A aortic dissection.
AB  - A case is reported of an 84-year-old woman with recurrent episodes of aphasia and
      right-sided weakness with spontaneous complete resolution associated with
      hypotension. She subsequently developed lower gastrointestinal bleeding, ischemic
      toes, and anuria without associated chest pain. An emergent transesophageal
      echocardiography showed a type A aortic dissection with aortic valve
      insufficiency and tamponade. Emergent thoracotomy was performed, which confirmed
      a severe acute type A aortic dissection. This is a reported case of acute
      painless aortic dissection presenting initially as recurrent transient ischemic
      attacks. The etiology of focal neurologic deficits should be crucially determined
      by an experienced clinician prior to thrombolytic administration. This case
      illustrates the importance of aortic disease in the etiology of acute stroke
      syndromes.

PMID- 12183772
TI  - Aneurysm morphology as a predictor of endoleak following endovascular aortic
      aneurysm repair: do smaller aneurysm have better outcomes?
AB  - Since the Food and Drug Administrations' approval of endovascular devices for
      abdominal aortic aneurysm (AAA) repair, clinicians have been relaxing the strict
      inclusion criteria present during the clinical trials. Although the long-term
      natural history of endoleaks remains unclear, attachment site leaks (type I) are
      believed to represent an ongoing risk for future rupture. We reviewed our
      experience with endovascular AAA repair to elucidate factors that predispose
      toward the development of endoleaks and found that larger AAAs are significantly
      more likely to have a short proximal neck and severe proximal angulation. These
      factors likely contribute to the significantly increased rate of type I endoleaks
      that occurred after endovascular repair of large AAAs. Small AAAs (<5) had the
      lowest rate of endoleaks overall (8.3%) and of type I endoleaks in particular
      (0%). We conclude that AAA size and morphology can be used to predict which
      aneurysms will experience attachment site endoleaks in their course; AAAs from
      4.5 to 5 cm in diameter may be particularly well suited for endovascular repair
      in this regard.

PMID- 12183773
TI  - Long-term results of infrageniculate bypass grafting using all-autogenous
      composite vein.
AB  - Infrageniculate (below-knee) bypass using all-autogenous composite vein requires
      multiple incisions, venovenostomy, and prolonged operating time. The purpose of
      this study was to evaluate the long-term results of this procedure, with
      comparisons to grafts created from single-segment greater saphenous vein (GSV) or
      polytetrafluoroethylene (PTFE). A total of 362 consecutive infrainguinal bypass
      grafts with infrageniculate distal target arteries were created in 283 patients
      in a single institution between January 1995 and December 2000. Comorbid
      conditions were common, including diabetes (58%), coronary artery disease (56%),
      prior lower extremity revascularization (41%), end-stage renal failure (20%), and
      prior coronary artery bypass grafting (18%). The indication for revascularization
      was limb salvage in 93% of cases. The grafts were constructed from single
      segments of GSV (n = 239), from two or more vein segments resulting in an all
      autogenous composite graft (n = 61), or from PTFE (n = 62). All-autogenous
      composite grafts were constructed using segments of ipsilateral or contralateral
      GSV (n = 49), upper extremity vein (n = 23), superficial femoral vein (n = 7), or
      lesser saphenous vein (n = 5). Infrageniculate all-autogenous composite vein
      grafts exhibited similar long-term results to those of GSV grafts, and far
      superior results to those of PTFE grafts. For patients with available autogenous
      segments, the all-autogenous composite vein graft is the conduit of choice.

PMID- 12183775
TI  - Abdominal aortic sarcoma: report of a case with long-term survival and review of
      the literature.
AB  - We present a case of an intimal epitheliod aortic sarcoma. Diagnosis was
      established after an aortic endarterectomy. The tumor was subsequently resected
      and an aortic graft was inserted. The patient underwent adjuvant chemotherapy.
      The patient is alive and free of metastatic disease at 48 months. Aortic tumors
      are rare, with an extremely poor prognosis and 1-year survival of 0-13%. The
      diagnosis is usually established postmortem, with metastatic disease being a
      common finding. The diagnosis should be suspected in patients with symptoms of
      nonatherosclerotic-related aortic occlusive disease or distal embolic events.
      Resection followed by adjuvant therapy and close follow-up can offer a prolonged
      survival for the patient with an extremely lethal aortic sarcoma.

PMID- 12183774
TI  - Duplex selection facilitates single point-of-service endovascular and surgical
      management of aortoiliac occlusive disease.
AB  - We attempted to optimize management of aortoiliac occlusive disease by using
      duplex imaging to aid in selection of favorable lesions for percutaneous
      transluminal angioplasty (PTA)/stenting, by avoiding nontherapeutic
      arteriography, and by providing single point-of-service care in which
      endovascular and open surgical reconstruction were combined. One-hundred
      consecutive patients with symptomatic (91 claudication, 9 limb threat) inflow
      occlusive disease based on clinical examination and physiologic testing underwent
      physician-directed duplex scanning of the infrarenal aorta through the femoral
      bifurcation. Iliac lesions suited to endovascular intervention were defined as
      focal (length <5 CM), high-grade stenoses with a peak velocity >300 cm/sec and
      velocity ratio >2 by duplex and were differentiated from unfavorable
      (diffuse/long iliac stenosis, occlusions, aneurysms, femoral occlusive disease)
      inflow lesions. Patients with favorable iliac lesions according to duplex were
      considered candidates for PTA/stenting in an endo-capable operating room, without
      prior diagnostic angiography. On the basis of duplex imaging, 38 patients
      possessed endovascularly favorable iliac lesions, 58 patients had unfavorable
      aortoiliofemoral disease, and 4 obese patients had inadequate studies. Duplex
      interpretation correctly classified disease distribution/severity in 92% of 50
      patients who subsequently underwent intraoperative or diagnostic arteriography.
      Thirty-one of the 45 (69%) total interventions performed in this patient group
      were based on duplex findings alone. Of 29 patients with favorable lesions by
      duplex scanning who had intervention, 25 (86%) received iliac PTA/stenting, while
      4 patients required inflow surgical reconstruction for nonfocal iliac disease
      demonstrated on operative arteriography. Duplex imaging correctly identified the
      need for concomitant outflow reconstruction/bypass in 11 of the 25 (44%) patients
      treated by iliac PTA/stenting. Primary and assisted patency rates of iliac
      PTA/stenting were 83% and 100% at 24 months by life-table analysis. Duplex
      imaging in patients with symptomatic aortoiliac occlusive disease can provide
      sufficient information to permit endovascular and surgical intervention without
      formal diagnostic arteriography in most patients.

PMID- 12183776
TI  - Management of rare mesenteric arterial branch aneurysms.
AB  - Mesenteric arterial branch aneurysms are rare. This study reports the Mayo Clinic
      experience from 1980 to 1998. We reviewed the medical records of 306 patients
      with visceral artery aneurysms evaluated at all three Mayo Clinic campuses from
      1980 to 1998. In this group, we discovered 12 (3.9%) patients with 14 aneurysms
      of the mesenteric branch arteries. In our small experience, colic aneurysms were
      more likely to rupture and therefore should be considered for intervention in
      patients with a reasonable operative risk.

PMID- 12183777
TI  - Early duplex-derived hemodynamic parameters after lower extremity bypass in
      diabetics: implications for mid-term outcomes.
AB  - Early postoperative changes in the hemodynamic parameters of infrainguinal bypass
      grafts in diabetics have not been well defined. We undertook this study to better
      define such changes in duplex-derived velocities and waveforms, and correlate any
      observed changes with intermediate-term outcomes. A prospective study of 68
      primary vein bypasses for limb salvage was carried out, with scans obtained
      intraoperatively, daily until discharge, and at 8- to 12-weeks intervals. During
      follow-up (12 +/- 6 months), 20 grafts developed stenoses, 17 occluded, and 8
      limbs were amputated. Most grafts show a variant of a biphasic waveform
      intraoperatively at the mid-graft (MG) and distal graft (DG) levels (54% and
      57%); 65% of waveforms remain unchanged during the first week, and 54% remain
      unchanged at 3 months. No duplex-derived factors were predictive of the
      development of stenoses. A number of parameters were predictive of ultimate graft
      thrombosis. Intraoperative MG velocity was higher in grafts that eventually
      remained patent (83 +/- 36 vs. 60 +/- 29 cm/sec; p <0.025). Grafts that remained
      patent also had a much lower decline in DG and distal native (DN) velocities from
      immediately postoperative to 8-12 weeks later, than grafts that eventually
      thrombosed (-3 +/- 35 vs. -44 +/- 43 cm/sec for DG, p <0.001; and -17 +/- 66 vs. 
      76 +/- 53 cm/sec for DN, p <0.04 respectively). In terms of limb salvage, when
      the MG or DG waveform worsened (from postoperation to 12 weeks later), amputation
      was more likely than when it remained unchanged or improved (MG 67% vs. 9% limb
      loss, p <0.04; DG 43% vs. 8% limb loss, p <0.04). We conclude that intensive
      graft duplex surveillance does not identify grafts likely to develop stenoses.
      However, a number of features allow the prediction of ultimate graft failure or
      limb loss.

PMID- 12183778
TI  - Endovascular aortic aneurysm repair in patients with renal dysfunction or severe
      contrast allergy: utility of imaging modalities without iodinated contrast.
AB  - Contrast-enhanced imaging studies are required for preoperative evaluation in
      patients undergoing endovascular aortic aneurysm repair; however, the use of
      iodinated contrast agents may not be suitable in patients with renal dysfunction
      or severe contrast allergy. The objective of this study was to evaluate the
      utility of imaging modalities without iodinated contrast in patients undergoing
      endovascular aortic aneurysm repair. A total of 297 patients underwent endo
      vascular repair of abdominal aortic aneurysms during a 6-year period ending in
      August 2001. Among them, 20 patients (6.2%), who underwent imaging studies
      without iodinated contrast because of either renal dysfunction or severe contrast
      allergy formed the basis of this study. Multiple non-iodinated contrast imaging
      studies were used, including gadolinium-enhanced magnetic resonance angiography
      (MRA), non-contrast computed tomography (CT), gadolinium or carbon dioxide (CO2)
      aortography, and intravascular ultrasound (IVUS). Hospital records were reviewed
      to evaluate the imaging study, renal function, perioperative morbidity, and
      clinical outcome of endo vascular aortic aneurysm repair. From the results of our
      study we concluded that endovascular aortic aneurysm repair can be performed
      safely in patients with renal dysfunction or severe contrast allergy utilizing
      non-iodinated contrast-based imaging modalities. IVUS is a useful intraoperative
      imaging modality, and postoperative endoleak surveillance can be performed using
      duplex ultrasound scanning to avoid risk of iodinated contrast exposure.

PMID- 12183779
TI  - Infected endovascular graft secondary to coil embolization of endoleak: a
      demonstration of the importance of operative sterility.
AB  - A 60-year-old male underwent endovascular repair of a 5.4-cm enlarging abdominal
      aortic aneurysm with intraoperative recognition of a type I endoleak. The
      endoleak was demonstrated to be arising from the left limb of the bifurcated
      prosthesis. An intravascular stent was placed in the limb near the origin of the
      common iliac artery and it appeared that the endoleak had sealed. However, 1
      month after operation a CT scan demonstrated a persistent, substantial size
      endoleak without aneurysm enlargement. Coil embolization of the endoleak was
      undertaken in the interventional radiology suite with apparent satisfactory
      result. Four days after embolization the patient developed abdominal pain and
      after 8 days fever and leukocytosis developed. Two weeks after embolization an
      abdominal CT and indium scan revealed an infected endovascular graft. By CT, the
      posterior wall of the aneurysm was destroyed and a peri-graft fluid collection
      with gas was present at the location of the coils. The patient was treated with
      graft and coil excision and autologous vein reconstruction. Endoluminal
      prostheses can be contaminated at the time of operative placement. However, an
      additional source of endoluminal graft infection can arise from secondary
      endovascular procedures for endoleaks and other graft complications. Since we
      began placing endovascular grafts at our institution in 1993, most coil
      embolizations have been performed in the interventional radiology suite. This
      experience of coil-induced infection causes us to consider performing this type
      of secondary intervention in the operating room environment.

PMID- 12183780
TI  - Transrenal versus infrarenal endograft fixation: influence on type I endoleaks.
AB  - The purpose of this study was to compare the rate of proximal type I endoleaks in
      patients undergoing endoluminal repair of infrarenal abdominal aortic aneurysms
      with endografts having either transrenal or infrarenal fixation. From September
      1998 to May 2000, 42 patients received endoluminal aortic grafts for the
      treatment of infrarenal abdominal aortic aneurysms. Patients received either
      transrenal or infrarenal devices, based on the surgeon's preference. All patients
      had infrarenal aortic neck lengths measuring at least 1.5 cm and proximal neck
      angulation of <60 degrees. The endoluminal grafts were oversized by 10-20%
      relative to the diameter of the infrarenal aorta. The presence of endoleaks was
      determined at the initial procedure by contrast angiography and during subsequent
      follow-up at 1 month and 3 months by CT scan or duplex ultrasound. No significant
      differences in the rate of proximal type I endoleaks can be demonstrated between
      transrenal and infrarenal device types in this small cohort. Proper patient
      selection is more important than type of proximal fixation in preventing
      endoleaks.

PMID- 12183781
TI  - Management of vascular complications following femoral artery catheterization
      with and without percutaneous arterial closure devices.
AB  - Percutaneous arterial closure devices allow earlier mobilization and discharge of
      patients after arterial catheterization than with manual compression for puncture
      site hemostasis. We reviewed our recent experience managing the complications of
      femoral artery catheterization with and without these devices on the vascular
      surgery service at a tertiary hospital. Thirty-one patients presenting over an 18
      month period with complications after femoral artery catheterization with manual
      compression (n = 21) or percutaneous arterial closure devices (n = 10) were
      retrospectively reviewed.

PMID- 12183782
TI  - Treatment of embolizing arterial lesions with endoluminally placed stent grafts.
AB  - The purpose of this study was to demonstrate the safety and efficacy of
      endovascular stent grafts for the management of embolizing arterial lesions.
      Eight patients who presented to Barnes-Jewish Hospital between June 2000 and June
      2001 with embolizing arterial lesions were treated with covered stents or stent
      grafts. All hospital records were retrospectively reviewed, and pertinent data
      extracted. Our results showed that endovascular stent grafts can be used
      successfully to exclude embolizing arterial lesions without increasing the risk
      of further embolization. Long-term follow-up will be necessary to assess the
      durability of this approach to embolizing arterial lesions.

PMID- 12183783
TI  - Pitfalls in achieving the Dialysis Outcome Quality Initiative (DOQI) guidelines
      for hemodialysis access?
AB  - The Dialysis Outcome Quality Initiative (DOQI) mandates that 50% of permanent
      hemodialysis (HD) access be native arteriovenous fistulae (AVFs). Recent reports
      have shown that when these guidelines are followed, the percentage of new AVFs
      can exceed DOQI guidelines. From July 1998 to July 2001, 330 HD access procedures
      were performed in an academic tertiary care center. Patients were categorized
      into two groups. Group I followed DOQI guidelines and underwent history and
      physical examination; duplex vein mapping; use of basilic vein transposition; and
      a postoperative protocol to determine maturation and start needle access in a
      stepwise progression. Group II had history and physical examination and basilic
      vein transposition was not used. Patient data were retrospectively reviewed.
      Overall, 100 (31%) HD shunts were AVFs. Group I (42/183, 23%) had significantly
      less AVFs (p = 0.005) than group II (58/147, 39%). For first-time placement of HD
      access, there was no significant difference (p = 0.95) in the percentage of AVFs
      in group I (26/62, 42%) and group II (29/68, 43%). For patients with prior
      history of HD access, significantly less AVFs (p <0.001) were placed in group I
      (16/121, 13%) than in group II (29/79, 37%). Group I had significantly less first
      time HDS (P = 0.03) than group II, 34% VS. 46%, respectively. AVF maturation for
      hemodialysis occurred in 79% of group I and 71% of group II (P = 0.52). There
      were no significant differences (P > 0.05) when comparing age, gender, and
      incidence of diabetes between the two groups. AVF formation based largely on
      duplex vein mapping in group I and lack of basilic vein transposition in group II
      contributed to the inability to achieve DOQI guidelines. Integration of knowledge
      and practice among vascular surgeons may help to avoid these pitfalls.

PMID- 12183784
TI  - [Self-training versus conventional physiotherapy in subacromial impingement
      syndrome].
AB  - AIM: This prospective, randomized study was aimed to compare the effect of a
      standardized self-training versus standard physiotherapist-supervised exercises
      in the non-operative treatment of shoulder impingement syndrome types Neer I and
      II. METHOD: 40 patients with subacromial impingement I/II were randomized to two
      groups. Group 1 performed a mostly isometric self-training after instruction by a
      physiotherapist, group 2 received prescriptions for physiotherapy and
      "strengthening exercises for the rotator cuff". Follow up was performed after 6
      and 12 weeks with the use of the constant score (unpondered). Patient
      satisfaction with the treatment was controlled by VAS (1 - 6). RESULT: After 12
      weeks, patients of group 1 had performed the exercises 5 x/week for 15 minutes.
      Patients of group 2 had received 30 sessions in average. Patients of group 1
      improved from a mean of 59 points (39.5 - 86) to a mean of 68 points (37 - 88)
      after 6 and 75 points (65 - 90) after 12 weeks. Patients of group 2 improved from
      60.5 points (41 - 83) to 67 points (39.5 - 92) and 72 points (43 - 93),
      respectively. Patient satisfaction was higher in the self-training group (1.9 :
      2.8). CONCLUSION: Strengthening of the centering muscles around the humeral head
      leads to good results in the non-operative treatment of subacromial impingement.
      Self-training after instruction showed no difference to physiotherapist
      supervised exercises in the non-operative treatment of subacromial impingement.

PMID- 12183786
TI  - [Comparison of the results of the surgical repair of full-thickness tears of the
      rotator cuff with and without resection of the lateral clavicle].
AB  - PURPOSE: Aim of this study was to compare the results of the surgical repair of
      full-thickness rotator cuff tears with and without resection of the lateral
      clavicle. METHODS: 102 patients were retrospectively observed by an independent
      observer for a mean follow-up of 21 months (12 - 42). 93 patients had medium to
      large sized tears (1 - 5 cm) and 9 had massive tears (> 5 cm). Additional
      resection of the lateral end of the clavicle was performed in 20 patients. The
      mean age of the 68 men and 34 woman was 57.3 years (28 - 80). For the evaluation
      the Constant score, the ASES score and the visual analogue scales for
      postoperative satisfaction, function, strength, pain and ADL were used. RESULTS:
      The subjective results were good to excellent in 79 patients (76 %), fair in 14
      patients (13.7 %) and poor in 9 patients (8.9 %), too. After surgery the Constant
      score was 87 % of the contralateral side for all patients, 89 % for group I and
      84 % for group II and the mean ASES score was 86 %, 87 % and 82 % of the
      contralateral side. Comparing the pre- and post-operative values on the visual
      analogue scale pain and disability in ADL were decreased highly significantly in
      all patients (p < 0.001). CLINICAL RELEVANCE: We conclude that in patients with a
      full-thickness rotator cuff tear the patient's satisfaction and function will
      improve after acromioplasty and rotator cuff repair. The results are not
      significantly influenced by an additional resection of the lateral clavicle.

PMID- 12183785
TI  - [Subacromial denervation as a treatment modality for patients with subacromial
      pathology].
AB  - PURPOSE: The purpose of the presented study was to valuate the question whether
      subacromial denervation alone is sufficient in patients with subacromial
      pathology. MATERIAL AND METHODS: 20 patients (male: 7; female 13) with
      subacromial pathology without anterior acomionosteophytes, rotator cuff tear,
      calcific tendinitis or ac-joint pathology underwent endoscopically controlled
      subacromial denervation. The procedure was performed with an HF device. Patients
      were followed up at 6 weeks, 3 and 6 months with the Constant score. RESULTS: The
      preoperative Constant score was 59 +/- 18. Postoperatively the Constant score
      increased to 78 +/- 18 after 6 weeks, up to 83 +/- 5 after 3 months and up to 85
      +/- 13 after 6 months. There was no difference between male and female patients
      nor between patients with different profession or athletic activity. We could not
      document any complication. Patients returned to work within 6 weeks after
      surgery. CONCLUSION: Patients without anterior acromion osteophytes and without
      rotator cuff tear may get good results with subacromial denervation alone and may
      not need acrornioplasty.

PMID- 12183787
TI  - [Isolated rupture of the subscapularis tendon in the overhead athlete - the
      result of chronical overuse?].
AB  - The case of a 27-year-old overhead athlete with chronic shoulder pain because of
      an isolated subscapularis tear without trauma is described. Arthroscopy has
      proven to be the appropriate method for detailed visualisation of the injury and
      facilitates the operative planning. Furthermore, arthroscopy closes the problem
      of a "diagnostic gap". In the presented case, the results at the two year follow
      up are excellent. The authors conclude that an operative approach is also
      justified in non-traumatic isolated ruptures of the subscapularis muscle.

PMID- 12183788
TI  - [Local treatment of periarthropathies with the 5-HT3-receptor-antagonist
      tropisetron].
AB  - All substances used in the local treatment for periarthropathies, such as local
      anesthetics, corticosteroids or botulinum toxin A, possess certain disadvantages.
      Finding alternatives to these agents in the local treatment of the disease
      therefore seems desirable. Comparative studies proved a local injection of the 5
      HT3 receptor antagonist, tropisetron (Navoban(R)), to be more effective than an
      injection of the local anesthetic prilocaine in treating periarthropathies of
      different localizations. A comparison between the local injection of 10 mg of
      depot dexamethasone combined with 60 mg of lidocaine and 5 mg of tropisetron
      showed that the two regimens had the same effect. These findings demonstrate that
      a local injection of 5 mg tropisetron does represent an alternative to the local
      treatment with corticosteriods plus local anesthetics. However, these results
      should be corroborated by additional studies.

PMID- 12183789
TI  - [Mineral analysis of roentgenologically defined calcifications in patients with
      chronic calcifying tendinitis of the rotator cuff].
AB  - AIM: Extracorporeal shockwave application (ESWA) is in clinical use to promote
      disintegration of symptomatic calcifications of the rotator cuff of the shoulder.
      However, disintegration of roentgenologically comparable calcifications of the
      rotator cuff is not always successfull. It is known from urologic stone
      lithotripsy that the susceptibility for disintegration of stone-like concrements
      depends on their mineral content. Therefore, in the present investigation the
      relative contents of calcium and phosphorus in rotator cuff calcifications were
      determined. METHOD: 39 surgically removed rotator cuff calcifications were
      analyzed by means of atomic emission spectrometry. RESULTS: The relative content
      of calcium of the rotator cuff calcifications was found to be 22.3 % +/- 5.7 %
      (mean +/- SD; 6.8 % - 32.4 %), that of phosphorus as 10.5 % +/- 2.4 % (2.7 % -
      14.4 %). The data neither depend on the gender of the patients nor on their age
      at the time point of surgical removal of the rotator cuff calcifications.
      CONCLUSION: Roentgenologically comparable calcifications of the rotator cuff
      demonstrated distinct individual differences concerning the relative contents of
      calcium and phosphorus. The present results may serve as the first indication
      that the susceptibility of rotator cuff calcifications for disintegration may
      depend on their relative contents of calcium and phosphorus.

PMID- 12183790
TI  - [Primary synovial chondromatosis of the shoulder].
AB  - AIM: To demonstrate the various patterns of primary synovial chondromatosis (PSC)
      around the shoulder and to discuss a therapeutic algorithm. METHOD: In this
      retrospective study, 6 patients with histologically proven PSC were operated on.
      The diagnosis was based on clinical examination, plain X-rays, ultrasonography
      and MRI in 5/6 patients. Also, a histological examination was done in all cases.
      According to the localisation of the disease, surgery was done by endoscopy
      alone, endoscopy together with open surgery or direct open surgery. RESULTS: In
      one case each, we saw an isolated disease of the subacromial bursa or the gleno
      humeral joint. In two cases, we found an intraarticular affection together with
      the biceps tendon sheath. The other two patients showed a massive periarticular
      deposition of loose bodies together with a defect of the rotator cuff. All
      patients with intraarticular disease (5/6) showed different stages of
      chondromalacia. In 5 of 6 patients all bodies could be removed at surgery. At
      follow-up after 36 months the patients subjectively rated the result as
      satisfactory to excellent. In the patients with total removal of the bodies, no
      recurrences were seen on plain X-ray or ultrasonography. CONCLUSION: PSC around
      the shoulder appears with a variable pattern. According to the possible late
      complications described in the literature (i. e., secondary osteoarthritis,
      involvement of the rotator cuff and secondary malignant transformation), we find
      operative treatment justified. Surgery addressing removal of loose bodies and
      partial synovectomy allows good results. The operative approach (endoscopy or
      open surgery) is related to the localisation and severity of the condition.

PMID- 12183791
TI  - [Shoulder arthroplasty - Clinical results in 171 patients].
AB  - AIM: Review and critical evaluation of 181 shoulder arthroplasties performed on
      171 patients between December 1992 and January 1997. METHOD: We performed 118
      hemiarthroplasties and 63 total shoulder replacements in 171 patients with an
      average age of 56.5 years. The patients were examined clinically and
      radiologically before surgery and followed-up for an average of two years. The
      Constant score was used for postoperative functional assessment. RESULTS: 46 % of
      the patients were very satisfied and 31 % were satisfied with the outcome. We
      found a significant pain reduction and an improvement of active joint function.
      The average Constant score was 34.9 preoperatively and 65.2 postoperatively.
      Overall, we found the best results after joint replacement in patients treated
      for avascular necrosis or fracture sequelae of the humeral head. A revision
      surgery had to be performed in 16 patients (8.8 %). CONCLUSION: The results of
      this study are encouraging and underline the growing importance of shoulder
      arthroplasty. The preoperative limited range of motion, previous surgeries, and
      the status of the rotator cuff are preoperative indicators for a favourable
      postoperative outcome. Preoperative planning, anatomical reconstruction, and an
      optimal rehabilitation programme are the keys for successful shoulder
      arthroplasty.

PMID- 12183792
TI  - [Can an insufficient posture of children and adolescents be verified
      instrumentally?].
AB  - 144 children aged 6 to 17 years were examined with the Lasar-Posture device which
      raises a perpendicular through the centre of gravity. To make an indirect
      postural examination possible and to classify posture, the courses of the gravity
      perpendicular, the shoulder centre, the greater trochanter femoris and the
      lateral ankle and their change during the Matthiass' test were determined.
      Additionally, spinal alignment, spine flexibility and the sufficiency of posture
      were assessed. RESULTS: The ability to achieve a sufficient posture correlated
      with age (p = 0,0004). The spinal alignment itself did not differ in the age
      groups but the hollow-round back showed a decreased ability to attain a
      sufficient posture (p < 0.0001). The spine flexibility measured with the Ott's
      test decreased with age (p = 0.0001). In relation to the gravity perpendicular,
      the shoulder centre moved forward with increasing postural insufficiency (p =
      0.0379). The course of the gravity perpendicular did not differ in the different
      types of spinal alignment but was always found in front of the lateral ankle. The
      greater trochanter of the children with a II degrees insufficiency at the
      beginning (p = 0.03/0.01) and end (p = 0.2/0.05) of the Matthiass' test was
      always in front of the gravity perpendicular in contrast to the other children.
      As expected, the shoulder centre was always behind the gravity perpendicular. It
      was found to be more ventral in healthy children than in those with a postural
      insufficiency (p = 0.01/0.004/0.005). CONCLUSION: Overall, a high rate of
      children with postural insufficiency was found. It is impossible to determine or
      classify them with the Lasar-Posture device. The future aim should be to develop
      a measuring technique that allows a standardised definition of posture and age
      related developmental variants.

PMID- 12183793
TI  - [Relationship of an increased internal rotation of the hip with pelvic tilt,
      spinal alignment and posture - does the so-called antetorsion syndrome exist?].
AB  - AIM: A cross-sectional study of pupils should show a possible relation between
      hip movement, posture and spinal alignment. METHODS: 143 children aged 6 to 17
      years were clinically examined with particular respect to internal rotation and
      extension of the hip, spinal alignment and posture to determine if the so-called
      antetorsion syndrome exists in children as a remnant of the uprising of man.
      RESULTS: Internal hip rotation decreased with age without any difference
      regarding the age between children with and without hip contracture. Children
      with hip flexion deformity had a significantly higher ability for internal hip
      rotation (p = 0.0471), but both hip extension and internal rotation were not
      related to spinal alignment (p = 0.5585/0.5612). On the other hand a normal
      posture is related with a "normal" back and age (p = 0.0004). The spinal
      alignment itself did not differ in the age groups. 30 % of the children with
      sufficient posture and 38 % of the ones with insufficient posture had a hip
      contracture. The latter showed an increased internal hip rotation by 12 degrees
      (p = 0.0079). CONCLUSION: On the basis of these results, a relationship between
      muscular performance, neuromuscular maturity, decreased hip extension and
      increased internal hip rotation can be assumed. This so-called antetorsion
      syndrome exists in 20 % of the examined children. A relation to the spinal
      alignment especially the hollow-round back, cannot be found.

PMID- 12183794
TI  - [Prognostic factors for avascular necrosis following talar fractures].
AB  - AIM: We performed an investigation of factors for avascular necroses after talus
      fracture and on the reliability of the Hawkins Sign. METHOD: From 1984 until 1997
      a total of 98 patients with 99 talus fractures were surgically treated. Of these,
      79 patients with 80 fractures were examined clinically and radiologically. The
      average postoperative interval was 6 years and 2 months. RESULTS: With respect to
      the 65 central fractures, the rate of necrosis amounted to 14 %, that of collum
      fractures to 17 %. Necroses arose solely in dislocated central fractures of the
      talus, type III and IV according to Marti/Weber fracture classification. The rate
      of necrosis rose with the degree of dislocation of the fractures. In 24 patients
      the Hawkins Sign could be retrospectively investigated. It proved to be a
      relatively reliable sign for vitality since only 1 out of 12 patients with
      positive or partial positive Hawkins Sign developed avascular necrosis. Neither a
      short interval between accident and operation, the age at the time of the
      accident, nor the ipsilateral fracture of the medial malleolus showed a necrosis
      preventive influence. In 5 out of 9 talus necroses the patients were very or
      mostly satisfied with the result of their treatment. CONCLUSION: The Hawkins Sign
      proved to be a relatively reliable sign for vitality of the talus after fracture.
      Risk for avascular necrosis increases according to the degree of fracture
      dislocation.

PMID- 12183795
TI  - [Can TOF MRA replace duplex and Doppler sonography in preoperative assessment of
      the carotid arteries? A prospective comparison and review of the literature].
AB  - AIM: To examine the quality and usefulness of time-of-flight MR-angiography and
      duplex-doppler sonography, respectively, in assessment of the extracranial
      arteries before cervical spine operations. METHODS: Patients scheduled for
      operations of the cervical spine had an MRI plus TOF as well as a duplex and
      Doppler scan. At the time of the examination the radiologist and the neurologist
      in charge were blinded for the study. Endpoints were not only the accuracy of the
      procedures but more so which method improved the preoperative process most.
      RESULTS: Twenty patients were examined so far. Only in one case did the result
      differ when a complete occlusion diagnosed sonographically was judged as a severe
      stenosis on MRA. One patient did not tolerate the MRA for the extra 5 minutes
      necessary, therefore a contrast-enhanced MRA was performed. MRA eased the
      preoperative process as imaging of the pathology and the carotids were realised
      in one step. The costs were slightly higher for MRA than for duplex-doppler
      sonography. CONCLUSION: TOF-MRA can replace the duplex-doppler examination in the
      preoperative assessment of the carotids and has the potential to streamline the
      preoperative time schedule. Similar to duplex and doppler, in order to be
      accurate enough the method requires a high degree of expertise from the
      radiologist.

PMID- 12183796
TI  - [DNA flow cytometry of bone metastases of different primary tumors].
AB  - AIM: Some human tumors of different primary localization metastasize preferably
      into the bone. This concerns especially kidney, breast, prostate and lung cancer.
      So far, the reason for this specific pattern of metastazing could not
      sufficiently be clarified. The aim of the study was the search for mutuality in
      the results of the DNA analysis of bone metastases of different primary tumors
      and their importance for prognosis and therapy. METHOD: In this study, the DNA
      content of 40 excised bone metastases of different primary localisation has been
      determined by flow cytometry. By means of the DNA distribution pattern, the
      percentage of tumor cells in the particular cell cycle phase as well as the
      respective ploidy condition have been calculated. RESULTS: Altogether, no
      preference of DNA diploid or DNA aneuploid stem cell lines could be found.
      Whether this can be applied for metastases of all primary tumors has not been
      clarified yet. The fact that, in 11 out of 12 tested cases of the same
      metastasis, DNA diploid as well as DNA aneuploid areas could be demonstrated,
      seems to be fundamental. CONCLUSION: There exist a high variability of the extent
      of dysregulation and the intensity of the growth of bone metastasis. This does
      not seem to be crucial for the preferable tendency to metastazise into the bone.
      Due to the often insufficient tumor amount for material extraction from different
      areas and the large amount of DNA diploid metastases after flow cytometry
      analysis there should be considered the additional use of pictorial analytical
      methods for the DNA ploidy and proliferation assessment. A knowledge of the
      intensity of the course and the degree of dysregulation of tumor cell
      proliferation of bone metastases is beneficial in order to estimate the prognosis
      and to design an individual therapy regime.

PMID- 12183797
TI  - [Reliability and validity of the upper limb DASH questionnaire in patients with
      distal radius fractures].
AB  - AIM: The purpose of the study was to verify test criteria of the upper-limb DASH
      questionnaire in patients with Colles' fractures. METHODS: 107 of 139 patients
      with Colles' fractures treated operatively were examined and asked to complete
      the questionnaire. To establish reliability, the item answers of all
      questionnaires were analysed by using Cronbach's Alpha correlation coefficient
      and corrected item total correlation. Construct validity was evaluated by
      comparing the DASH points with clinical measures according to Gartland/Werley and
      Castaing (Spearman correlation coefficient). Discriminant validity was assessed
      by comparing the DASH points of patients with AO-type A/B fractures and AO-type C
      fractures (Mann-Whitney U-Test). RESULTS: 2.7 percent of all questionnaires were
      unusuable. The time to fill out the questionnaire was on average 12 minutes.
      Cronbach's alpha values were high in all scales (alpha > 0.8). No items were
      found unsuitable (corrected item total correlation > 0.5 in 28 of 30 questions).
      DASH scores were correlated with ROM deficits and clinical measures of wrist
      function (r = 0.53; r = 0.59; r = 0.52, p < 0.01). The questionnaire could
      discriminate patients with different fracture types (p < 0.05). CONCLUSIONS: DASH
      is a workable, reliable and valid instrument for patients with Colles' fractures.

PMID- 12183798
TI  - [Using the Lequesne questionnaires for patients with hip and knee disabilities in
      daily routine to reflect the quality of outcome in rehabilitation].
AB  - AIM: Studies in rehabilitation research put great value on patients' self
      assessment. Patients with hip or knee diseases who need an orthopaedic
      rehabilitation suffer mainly pain, reduction of walking distance and other
      disabilities that impact on the activities of daily life. The Lequesne scores for
      the hip and knee are an indicator to show the degree of disabilities. The aim of
      the study was to prove that the Lequesne indices are reliable instruments for the
      individual to express the outcome of rehabilitation. We tested the Lequesne
      indices in daily clinical work, in the handling and in the acceptance. METHOD:
      Since May 1999 the rehabilitation center Bad Eilsen uses the Lequesne
      questionnaires as self-report questionnaire instruments for patients with hip and
      knee disabilities. 145 patients with hip and 122 patients with knee diseases
      filled in the questionnaires correctly and handed them back. RESULTS: The
      Lequesne indices are able to show developments in both directions; improvement as
      well as change for the worse. The Lequesne questionnaires are helpful to complete
      the common clinical parameters. CONCLUSION: Using the Lequesne questionnaires as
      a self-report instrument in our daily routine we are able to obtain a good
      reflection of individual health condition and the quality of outcome in
      rehabilitation.

PMID- 12183799
TI  - [Skin cancer].
AB  - The current status, clinic, causes and prevention strategies of malignant tumours
      of the skin are described. Dermatologists, physicians and health professionals
      have made tremendous efforts to improve the public education and early detection
      of these tumours especially during the last decade. Further campaigns and
      continual medical education are demanded to continue this improvement for
      patients and public health system.

PMID- 12183800
TI  - [Epidemic nephropathy. An important differential diagnosis of acute renal failure
      in Reutlingen, an endemic area].
AB  - BACKGROUND AND OBJECTIVE: Hantavirus ("epidemic") nephropathy (HN), or
      hemorrhagic fever with renal syndrome (WHO nomenclature), is an infection caused
      by strains (e.g. Puumala) of Hantavirus, which is often accompanied by acute
      renal failure. Although its typical symptomatology has been fully reported, it is
      rarely included in the differential diagnosis of renal nephropathy. This study
      investigated whether, in the presence of typical symptoms, specific search for a
      certain constellation of laboratory values in association with a typical history
      can more often provide the diagnosis of HN. PATIENTS AND METHODS: 18 patients (4
      females, 14 males; average age 41 years) fulfilled the following inclusion
      criteria: abnormal values for creatinine, LDH and C-reactive protein, proteinuria
      and hematuria, as well as thrombocytopenia in conjunction with fever, back- and
      headache. After the diagnosis had been confirmed by demonstrating antibodies
      against the Puumala strain of hantavirus, follow-up included laboratory tests and
      clinical observation. RESULTS: All patients fully recovered without any sequelae.
      There was a clearly increased frequency of cases at the Reutlingen Clinic
      compared with the previous years (maximally 7 cases per year in 1995-1999). The
      incidence in the Reutlingen region was probably at least 6.5/100 000 inhabitants.
      CONCLUSION: At least in endemic regions HN is one of the most common causes of
      acute renal failure. The increase of cases can, among other reasons, be explained
      by the described prospective diagnostic schema. But climatic factors with changes
      in the density of the vector (bank vole) cannot be excluded.

PMID- 12183802
TI  - [Bilateral adrenal hemorrhage occurring two times in primary antiphospholipid
      syndrome (APS). Anticoagulation as treatment of hemorrhage].
AB  - HISTORY: A 56-year-old man was admitted for investigation of abdominal pain
      radiating to the back. The patient was known to suffer from APS and autoimmune
      thrombocytopenia, and was therefore treated with oral anticoagulants. The
      clinical examination was normal. INVESTIGATIONS: Ultrasound detected an area with
      low echogenicity in the region of the right adrenal gland. A CAT scan identified
      this mass as an adrenal hemorrhage. DIAGNOSIS AND TREATMENT: Anticoagulation
      treatment was discontinued because the bleeding and thrombocytopenia and the
      patient's pain subsided. A few days later, he experienced similar pain, this time
      radiating to the left side. A second hematoma was discovered in the left adrenal
      gland. The patient developed symptoms of acute adrenal insufficiency, which
      subsided after therapy. The bilateral adrenal hemorrhage was considered to be
      secondary bleeding following thromboses in the venous system of the adrenal
      gland. The thromboses were due to the underlying APS. Anticoagulation therapy was
      resumed, and the patient's condition stabilised without further complications.
      CONCLUSION: The cessation of anticoagulation therapy in this patient
      paradoxically led to hemorrhage, this time of the contralateral adrenal gland.
      Unilateral and, especially, bilateral adrenal bleeding should give rise to the
      suspicion of thrombophilic disorders such as APS or heparin-induced
      thrombocytopenia (HIT); for which careful anticoagulation is the treatment of
      choice.

PMID- 12183801
TI  - [Providing or withholding treatment: the role of the patient's wish and
      priorities in palliative care].
AB  - BACKGROUND AND OBJECTIVE: Medical law and ethics require that intervention be
      based on patients' wishes. However, in particular the presumed wish of the
      patient, is often difficult to establish. Discussions with patients may want to
      inform or influence the patient's wishes. We investigated how far clinical
      decisions recognize the patient's wishes and how the presumed wishes of the
      patient is established and respected. PATIENTS AND METHODS: 503 physicians (25.6
      % women; mean age 36.3) in 49 departments of the universities Bochum and
      Magdeburg filled in a validated questionnaire. RESULTS: 86,2 % of the physicians
      questioned ranked the patient's wish as important or very important. However,
      54,4 % tried to modify it. Advanced directives play the most important role when
      the patient is unable to communicate. Danger to life and suicide are reasons for
      clinical decisions against the patient's wishes. But it is the main reason to end
      a causal therapy in terminally ill patients, especially in experienced
      physicians' opinion. CONCLUSIONS: Patients will plays a prominent role in
      treatment decisions; Even more so, physicians follow patients' wishes when
      withholding or withdrawing treatment. Our study could not find out how widely
      information of the patient plays a role in altering the patient's wishes in a
      paternalistic manner. Given a relative unfamiliarity with advance directives,
      affirmative attitudes towards their recognition are remarkable. As far as
      palliative and comfort care for terminal patients is concerned, contrary to
      widely voiced concern, clinicians do not have priorities different from those
      used in hospice care.

PMID- 12183803
TI  - [Epigenetics: significance for tumor genesis and clinical features].

PMID- 12183804
TI  - [Radiosynoviorthesis. An efficient form of local treatment for inflammatory joint
      diseases].

PMID- 12183806
TI  - [When patients pocket the physicians' fees].

PMID- 12183805
TI  - [Aggression and violent crime associated with schizophrenia].

PMID- 12183807
TI  - [Is chelation therapy in coronary heart disease useful?].

PMID- 12183808
TI  - [Management of patients with type-2 diabetes. Results in 12 general practices].

PMID- 12183809
TI  - [Prevention and disease management of chronic diseases].

PMID- 12183810
TI  - [Test strip analysis and urinary sediment].

PMID- 12183811
TI  - [Is the inflammation escaping out of hands?].

PMID- 12183812
TI  - [Patients with fractures are in the front line for osteoporosis treatment but how
      to treat?].

PMID- 12183813
TI  - [Practice guidelines and the psychiatric treatment in practice].

PMID- 12183814
TI  - [Trophoblastic diseases--a group of rare diseases].

PMID- 12183815
TI  - [Diagnosis and treatment of tennis elbow].

PMID- 12183816
TI  - [Delivery of fetus with breech presentation--vaginal delivery or cesarean
      section?].

PMID- 12183817
TI  - [Cardiovascular ffects of COX-2 selective anti-inflammatory agents].

PMID- 12183818
TI  - [Vomiting in an immigrant during early pregnancy].

PMID- 12183819
TI  - [Health status of the school children].

PMID- 12183820
TI  - [Is unfractionated heparin still needed?].

PMID- 12183821
TI  - [Laboratory diagnostics of susceptibility to venous thrombosis].

PMID- 12183822
TI  - [Treatment guidelines for deep venous thrombosis and pulmonary embolus].

PMID- 12183823
TI  - [Local intravenous thrombolytic therapy and intravascular surgical procedures].

PMID- 12183824
TI  - [Venous thrombosis during pregnancy].

PMID- 12183825
TI  - [Treatment of deep venous thrombosis at home].

PMID- 12183826
TI  - [Thrombosis in spite of warfarin--what should be done?].

PMID- 12183827
TI  - [Schizophrenia].

PMID- 12183828
TI  - Investigator profile. Interview by Vicki I. Glaser.

PMID- 12183829
TI  - Human umbilical cord blood cells: how useful are they for the clinician?

PMID- 12183830
TI  - Mechanisms that regulate silencing of gene expression from retroviral vectors.
AB  - The propensity of retroviruses toward transcriptional silencing limits their
      value as gene therapy vectors. Silencing has been shown to be particularly robust
      when stem cells are used for transduction, posing a significant problem for gene
      therapy of hematologic diseases. Stability of proviral expression with newer
      generation vectors is significantly improved over that obtainable with original
      vectors based on Moloney murine leukemia virus (MoMLV). However, strategies to
      increase resistance further to retroviral silencing are needed, because newer
      generation vectors have been shown to remain prone to a significant degree of
      silencing that could limit their efficacy as gene therapy vectors. Proviral
      silencing has been attributed to known mechanisms of cellular gene repression,
      such as DNA methylation and histone modification, as well as uncharacterized
      mechanisms that act independently of DNA methylation. A further understanding of
      transcriptional silencing that occurs in stem cells and during hematopoietic
      development is needed for design of effective vectors for gene therapy of
      hematologic diseases.

PMID- 12183831
TI  - Gene therapy of lymphoma.
AB  - Gene therapy offers new and promising treatment for patients with hematological
      malignancies. Tumor cells--lymphoma cells, for example--are possible targets for
      gene therapy. In general, gene therapeutic approaches require efficient gene
      transfer into host cells and sufficient transgene expression. Although many
      methods of gene transfer into mammalian cells exist, most do not allow efficient
      DNA transfer into primary lymphocytes. In contrast to gene transfer into tumor
      cells and many other cell types, which can be successfully performed using a
      variety of methods, the efficient expression of foreign DNA in lymphoma cells
      presents unique problems and challenges, requiring a careful selection of the
      mode of gene transfer. In this review, we discuss the current strategies for gene
      therapy in the treatment of lymphoma. We also summarize the current gene transfer
      methods for lymphoma cells and efficiency of transgene expression.

PMID- 12183832
TI  - Analysis of acute myelogenous leukemia: preparation of samples for genomic and
      proteomic analyses.
AB  - During the last decade, several large clinical studies have demonstrated that
      analysis of chromosomal abnormalities is an essential basis for therapeutic
      decisions in patients with acute myelogenous leukemia (AML), and cytogenetic
      studies should now be regarded as mandatory both for routine treatment and as a
      part of clinical investigations in AML. However, new techniques for detailed
      genetic characterization and analysis of gene expression as well as protein
      modulation will become important in the further classification of AML subsets and
      the development of risk-adapted therapeutic strategies. In this context, we
      emphasize the importance of population-based clinical studies as a basis for
      future therapeutic guidelines. Such studies will then require the inclusion of
      patients at small clinical centers without specialized hematological research
      laboratories. To document a high and uniform quality of the laboratory
      investigations, it will be necessary to collect material for later analysis in
      selected laboratories. In this article, we describe current methods for
      collection of biological samples that can be used for later preparation of DNA,
      RNA, and proteins. With the use of gradient-separated AML cells, it should be
      possible to establish the necessary techniques for collection and handling of
      biological samples even at smaller centers, and complete collections from all
      included patients should then be possible even in population-based clinical
      studies.

PMID- 12183833
TI  - Engraftment of post 5-fluorouracil murine marrow into minimally myeloablated (100
      cGy) murine hosts.
AB  - Minimal myeloablative approaches are now being widely applied in the treatment of
      different hematological malignancies. One hundred cGy whole-body irradiation is a
      stem-cell-toxic, relatively non-myelotoxic treatment that allows for relatively
      high levels of donor chimerism. 5-Fluorouracil (5-FU) treatment leads to a
      relative concentration of high proliferative potential-colony-forming cell (HPP
      CFC) and is an approach that has been used to induce in vivo progenitor/stem cell
      cycling to facilitate retroviral integration in gene therapy approaches. We have
      now evaluated the capacity of marrow harvested 1, 2, 6, or 12 days after 5-FU
      treatment (150 mg/kg) to engraft in 100 cGy-treated female BALB/c mice.
      Engraftment was assessed at 3, 10, and 24 weeks. A rapid induction of an
      engraftment defect occurred 1 day post 5-FU and persisted through day 6 with a
      recovery by day 12. To evaluate cell cycle status of normal and 5-FU-treated
      marrow cells, male donors received hydroxyurea (900 mg/kg i.v.) or phosphate
      buffered saline (PBS), 2 h prior to marrow harvest and transplantation into
      submyeloablated female recipients. Engraftment levels were similar for
      hydroxyurea-treated mice and controls. Thus, these studies show transiently
      defective engraftment of 5-FU-treated marrow into submyeloablated hosts, which
      may be related to the cell cycle status of the stem cells.

PMID- 12183835
TI  - Successful extracorporeal photochemotherapy for chronic graft-versus-host disease
      in pediatric patients.
AB  - A total of 254 extracorporeal photochemotherapy (ECP) procedures were performed
      in 8 children (median age 10 years; range 5-15) with extensive resistant chronic
      graft-versus-host disease (GVHD). ECP was carried out in the pediatric
      environment using a Cobe Spectra separator and UV-MATIC irradiator. A peripheral
      venous with a single-lumen permanent central catheter access (69% of ECP
      apheresis) or a dual-lumen permanent central catheter access (26% of ECP
      apheresis) were used preferentially. A median platelet decrease of 17% (0-71) (p
      = 0.0001) and median hemoglobin level decrease of 15 g/L (0-31)(p = 0.0001) were
      noted following each ECP-apheresis. However, none of the patients had profound
      thrombocytopenia or anemia. Two minor episodes of catheter related-bacteriemia
      (Staphylococcus aureus) were noted (2310 catheter-days). A negative correlation
      was found between lymphocyte collection efficacy (median = 38%) and pre ECP
      apheresis lymphocyte count (r = 0.4, p = 0.00001). The median of 5 x 10(7)
      lymphocytes/kg (0.1-50.10(7)/kg) was irradiated in each procedure. All patients
      are alive and well, and 7/8 experienced a dramatic improvement in their cutaneous
      status. Liver and gut disease resolved completely in 4/6 and 5/5 patients,
      respectively. In all patients, a concomitant immunosuppressive therapy was
      stopped (5/8) or considerably reduced (3/8). Five patients with more than 2 years
      follow-up after discontinuation of ECP are in remission with no immunosuppression
      treatment. They have normal growth rates and normal school and sport activity.
      Our study shows that ECP is beneficial, well tolerated, and can be safely used
      for chronic GVHD treatment even in young children with low body weight and a poor
      performance status. We believe that having a dedicated pediatric environment
      together with an experienced, motivated, and specifically pediatric team is of
      crucial importance for improving patient's acceptance of this long-term
      therapeutic program.

PMID- 12183834
TI  - Decreased stroma adhesion capacity of CD34+ progenitor cells from mobilized
      peripheral blood is not lineage- or stage-specific and is associated with low
      beta 1 and beta 2 integrin expression.
AB  - Molecular mechanisms leading to mobilization of hematopoietic cells from bone
      marrow (BM) to peripheral blood (PB) involve modulation of adhesion molecule
      expression on these cells that probably result in changes in adhesion capacity to
      the microenvironment. However, it is not clear whether these changes involve
      different stages or lineages of progenitor cells. In this study, we compared the
      capacity of mature and immature clonogenic progenitor cells from granulocyte
      colony-stimulating factor (G-CSF)-mobilized PB and normal BM CD34+ cells to
      adhere to complete marrow stroma. This functional capacity was assessed
      concurrently with molecular expression on CD34+ cells of integrins VLA-4 (alpha
      4/beta 1), VLA-5 (alpha 5/beta 1), and LFA-1 (alpha L/beta 2) by interindividual
      (between mobilized PB and normal BM) and intraindividual (between mobilized PB
      and steady-state BM and PB in the same patient) analysis. The proportion of
      adherent clonogenic progenitor cells was significantly lower in PB than in BM,
      not only for total progenitor cells but also for mature and immature progenitor
      cells, and the difference was found for granulocytic and particularly for
      erythroid lineages. The lower adhesion capacity of PB CD34+ cells to stroma was
      associated with decreased expression (signal/noise MFI ratio) of integrin alpha
      4, beta 1, alpha L, and beta 2 chains whereas that of alpha 5 chain did not
      differ from BM cells with the lowest expression level. Similar differences in
      integrin expression levels were also found between mobilized PB and steady-state
      BM CD34+ cells in the same patient except for the alpha L chain. Moreover, we
      demonstrated for the first time a strong positive correlation between mobilizing
      capacity and expression levels on mobilized CD34+ cells for the LFA-1 alpha L
      chain but not for VLA-4 or VLA-5. In conclusion, the decreased adhesion capacity
      of mobilized PB progenitor cells to stroma involves different maturation stages
      and different lineages. This is associated with down-regulation of integrins VLA
      4 and LFA-1, but mobilizing capacity appears positively correlated with LFA-1
      levels.

PMID- 12183837
TI  - Peripheral blood stem cells differ from bone marrow stem cells in cell cycle
      status, repopulating potential, and sensitivity toward hyperthermic purging in
      mice mobilized with cyclophosphamide and granulocyte colony-stimulating factor.
AB  - Peripheral blood stem cells (PBSCs) are increasingly used in autologous stem cell
      transplantations. We investigated the mobilizing effect of a combined
      cyclophosphamide (CTX) and granulocyte colony-stimulating factor (G-CSF)
      treatment on progenitor cells (STRA) and primitive stem cells (LTRA) in normal
      and splenectomized CBA/H mice. This combined treatment not only resulted in
      mobilization but also in expansion of hematopoietic stem cell subsets. The latter
      phenomenon was somewhat suppressed in splenectomized animals, but in these mice
      an enhanced mobilization of STRA and LTRA cells into the peripheral blood was
      observed. Furthermore, we studied the engraftment potential of mobilized PBSCs.
      Mice transplanted with PBSCs engrafted significantly better compared to mice
      transplanted with bone marrow stem cells from control and mobilized mice. The
      repopulation curve was characterized by a less-deep nadir indicating that the
      differences occur during the initial phase after transplantation. Contamination
      of autologous PBSC transplants with malignant cells is noticed frequently and is
      the basis for urging the use of purging modalities. Here we used hyperthermia and
      found that the mobilized progenitor cells in peripheral blood are more resistant
      to hyperthermia than those in the bone marrow (i.e., a survival of 11 +/- 5%
      after 90 min at 43 degrees C for peripheral blood progenitors, compared to 0.5 +/
      0.4% in bone marrow of mobilized animals and 1.6 +/- 0.5% in normal animals,
      respectively). Hyperthermic purging does not eliminate the superior repopulating
      features of a PBSC graft, as is demonstrated by an increased median survival time
      of lethally irradiated mice transplanted with purged PBSCs. In conclusion, our
      data demonstrate that CTX + G-CSF-mobilized PBSCs have an enhanced engraftment
      potential concomitantly with a decreased cycling activity and hence a decreased
      hyperthermic sensitivity. These findings support the use of these mobilized PBSCs
      for autologous stem cell transplantation and strengthen the basis for using
      hyperthermia as a purging modality.

PMID- 12183836
TI  - Proteolytic enzyme levels are increased during granulocyte colony-stimulating
      factor-induced hematopoietic stem cell mobilization in human donors but do not
      predict the number of mobilized stem cells.
AB  - Previous studies from our laboratory indicate that functional, mature neutrophils
      are essential for interleukin-8 (IL-8)-induced stem cell mobilization. To study a
      possible role of neutrophils in granulocyte colony-stimulating factor (G-CSF)
      induced hematopoietic mobilization, we assessed the number of circulating CD34+
      cells in healthy allogeneic stem cell donors on days 3, 4, and 5 of mobilization
      for comparison with the number of peripheral blood neutrophils and the plasma
      levels of IL-8, Flt3 ligand (FL), matrix metalloproteinase-9 (MMP-9), and human
      neutrophil elastase (HNE). Thirty-seven of 45 donors required 1 day of apheresis
      to obtain 5 x 10(6) CD34+/kg recipient body weight (high responders), the
      remaining 8 donors required 1 extra day of apheresis on day 6 (low responders).
      On day 5, CD34+ numbers in the blood were significantly highe in high responders
      (116 x 10(3) +/- 10.4/ml) than in low responders (54.1 x 10(3) +/- 10.3, p <
      0.001). In all donors, MMP-9 and HNE levels were increased compared to
      nonmobilized individuals, but in high responders, plasma MMP-9 levels on days 3-5
      of mobilization were substantially higher than in low responders (p < or = 0.02
      for MMP-9 and p = 0.89, p = 0.05 and p = 0.52 for HNE on days 3, 4, and 5,
      respectively). These results are in accordance with the hypothesis that
      neutrophils play a role in G-CSF-induced mobilization through the release of
      proteases such as MMP-9 and elastase. No change in plasma levels of IL-8 or Flt3
      ligand was observed, suggesting that these cytokines do not play a role in stem
      cell mobilization. However, because stem cell numbers could not be predicted by
      proteolytic enzyme levels and/or neutrophil numbers, other undefined factors may
      be more important.

PMID- 12183838
TI  - Serum Flt3 ligand variation as a predictive indicator of hematopoietic stem cell
      mobilization.
AB  - Flt3 ligand (FL) is a good indicator of bone marrow (BM) cellularity, having a
      reciprocal relationship with white blood cell (WBC) count in aplastic anemia and
      chemotherapy-induced neutropenia. In this report, serum FL level was measured by
      enzyme-linked immunosorbent assay (ELISA), in 16 consecutive patients undergoing
      autologous peripheral stem cell transplantation, with an average of 12 selected
      levels for each patient based on major changes of WBC counts at different
      procedure stations. We found a significant increase of serum FL level at the WBC
      nadir after mobilization chemotherapy and a more dramatic increase at the WBC
      nadir post transplantation, consistent with a more profound BM aplasia after
      myeloablative chemotherapy as compared to high-dose cyclophosphamide used for
      mobilization. Hence, we reproduced the reciprocal relationship between serum FL
      and BM cellularity. A direct correlation between the increase of FL level after
      mobilization chemotherapy and the length of mobilization was also established,
      which may help physicians, at the individual patient level, to predict the time
      of stem cell collection. Finally, we showed a direct correlation between the
      peripheral CD34+ count at the time of stem cell collection and the peak FL level
      after transplantation, which can reflect BM stromal cell function. Our results
      suggest that variation of serum FL level may be used as predictive indicator of
      hematopoietic stem cell (HSC) mobilization.

PMID- 12183839
TI  - CD44-mediated hematopoietic progenitor cell adhesion and its complex role in
      myelopoiesis.
AB  - During hematopoiesis in the bone marrow (BM), hematopoietic progenitor cells
      (HPC) proliferate and differentiate in intimate contact with BM stromal cells in
      a highly regulated interplay among cytokines, chemokines, and adhesion molecules.
      Using the mouse BM stromal cell line MS-5 as immunogen, we raised monoclonal
      antibodies (mAb) against surface proteins that could participate in interactions
      between HPC and stroma. Flow cytometry and immunodepletion analysis indicated
      that two antibodies, MA-8 and MA-2, recognized CD44. Although MA-8 and another
      anti-CD44 antibody, IM7.8.1, blocked adhesion of hematopoietic cells to
      hyaluronate, adhesion to BM stroma was notably increased by these mAb, suggesting
      minor roles for CD44/hyaluronate interaction and the triggering of additional
      adhesion pathways upon CD44 engagement. The presence of MA-8 in Dexter-type long
      term BM cultures (LTBMC) only slightly inhibited production of myeloid cells, and
      the number of myeloid progenitors (measured as CFU-GM) in the supernatants of
      LTBMC performed with MA-8 was similar to those carried out with control
      antibodies. Instead, IM7.8.1 completely blocked myelopoiesis, whereas an anti
      alpha 4 integrin mAb increased CFU-GM amounts. In summary, two anti-CD44
      antibodies with similar effects in cell adhesion showed notable differences in
      myelopoietic cultures, indicating the structural and functional complexity of the
      CD44 molecule.

PMID- 12183840
TI  - Reinjection of ex vivo-expanded primate bone marrow mononuclear cells strongly
      reduces radiation-induced aplasia.
AB  - To assess the therapeutic efficacy of ex vivo-expanded hematopoietic cells in the
      treatment of radiation-induced pancytopenia, we have set up a non-human primate
      model. Two ex vivo expansion protocols for bone marrow mononuclear cells (BMMNC)
      were studied. The first consisted of a 7-day culture in the presence of stem cell
      factor (SCF), Flt3-ligand, thrombopoietin (TPO), interleukin-3 (IL-3), and IL-6,
      which induced preferentially the expansion of immature hematopoietic cells [3.1
      +/- 1.4, 10.0 +/- 5.1, 2.2 +/- 1.9, and 1.0 +/- 0.3-fold expansion for
      mononuclear cells (MNC), colony-forming units-granulocyte-macrophage (CFU-GM),
      burst-forming units erythroid (BFU-E), and long-term culture initiating cells
      (LTC-IC) respectively]. The second was with the same cytokine combination
      supplemented with granulocyte colony-stimulating factor (G-CSF) with an increased
      duration of culture up to 14 days and induced mainly the production of mature
      hematopoietic cells (17.2 +/- 11.7-fold expansion for MNC and no detectable BFU-E
      and LTC-IC), although expansion of CFU-GM (13.7 +/- 18.8-fold) and CD34+ cells
      (5.2 +/- 1.4-fold) was also observed. Results showed the presence of mesenchymal
      stem cells and cells from the lymphoid and the megakaryocytic lineages in 7-day
      expanded BMMNC. To test the ability of ex vivo-expanded cells to sustain
      hematopoietic recovery after radiation-induced aplasia, non-human primates were
      irradiated at a supralethal dose of 8 Gy and received the product of either 7-day
      (24 h after irradiation) or 14-day (8 days after irradiation) expanded BMMNC.
      Results showed that the 7-day ex vivo-expanded BMMNC shortened the period and the
      severity of pancytopenia and improved hematopoietic recovery, while the 14 day ex
      vivo-expanded BMMNC mainly produced a transfusion-like effect during 8 days,
      followed by hematopoietic recovery. These results suggest that ex vivo expanded
      BMMNC during 7 days may be highly efficient in the treatment of radiation-induced
      aplasia.

PMID- 12183842
TI  - Cardiovascular risk in special populations: hypertensive disease in women.
      Introduction.

PMID- 12183841
TI  - Dynamics of CD34+ progenitor cells following allogeneic bone marrow
      transplantation in Ph1+CML--an immunohistochemical study on 113 patients with
      sequential trephine biopsies.
AB  - A retrospective immunohistological and morphometric study was performed on bone
      marrow trephine biopsies derived from 113 patients with Philadelphia chromosome
      positive chronic myeloid leukemia (Ph(1+)-CML) before and at standardized
      intervals following allogeneic transplantation (BMT) with full unmanipulated
      marrow specimens. The purpose of this investigation was to quantify CD34+
      progenitor cells and to determine their dynamics during the post-transplant
      period. Moreover, we tried to correlate their number with corresponding changes
      in the amount of nucleated erythroid precursors and megakaryocytes including pro-
      and megakaryoblasts and the fiber content. Monitoring the quantity of precursors
      after BMT revealed a very rapid recovery in comparison to a control group.
      However, a more detailed evaluation showed that at day 22 +/- 6 a higher number
      of progenitor cells was significantly associated with an earlier independence for
      platelet transfusion and also with a more pronounced growth of erythro- and
      megakaryopoiesis including their precursor cells. Furthermore, a slight increase
      in the density of the fibrous matrix (reticulin fibers) was present in these
      patients that were characterized by a more favorable engraftment. The latter
      feature sheds some light on the complex pathomechanisms of homing and
      differentiation of progenitors. In confirmation with in vitro findings, this
      phenomenon is dependent on proper anchoring sites to the fibrous bone marrow
      stroma. Finally, the size of a full BM graft exerted a distinctive influence on
      the number of CD34+ precursors in the early post-transplant period. In
      conclusion, the present study has validated a number of BM features by focusing
      on the CD34+ progenitor cells and associated hematopoietic reconstitution
      including reticulin fibers and precursor cells of the erythroid and megakaryocyte
      lineage, which are not readily evaluable by fluorescence-activated cell sorting
      (FACS) analysis.

PMID- 12183843
TI  - Endothelial function in hypertension: role of gender.
AB  - Endothelium plays an important role in the modulation of vascular tone and
      structure mainly through the production of nitric oxide (NO), which causes local
      vasodilation and counteracts processes leading to atherothrombosis. A
      dysfunctioning endothelium, characterized by reduced NO availability owing to
      impairment of the L-arginine-NO pathway and, above all, to production of oxygen
      free radicals, can impair local vasomotion and promote the development of
      atherosclerosis and of atherothrombotic vascular events. Aging is associated with
      endothelial dysfunction both in normotensive subjects and in hypertensive
      patients, and hypertension seems to induce earlier onset of those mechanisms
      (i.e. impairment of the L-arginine-NO pathway and oxidative stress) that cause
      age-related endothelial dysfunction. Premenopausal normotensive women are
      protected against the deleterious effect of aging on endothelial function, and
      age-related impairment of endothelial function is attenuated in premenopausal
      hypertensive women. This protective effect on endothelial function seems to be
      mediated by endogenous estrogen, which preserves NO availability by activating
      the L-arginine-NO pathway in normotensive women and, again, by activating this
      pathway but above all by inhibiting oxidative stress in hypertensive women. Thus,
      the protective effect of endogenous estrogen on endothelial function could be a
      plausible mechanism contributing to the lower cardiovascular risk of
      premenopausal women. Finally, whether endogenous androgen can impair endothelial
      function is still an unsolved issue since data concerning the effect of
      testosterone on endothelial function are scanty and contradictory.

PMID- 12183844
TI  - Is menopause an independent cardiovascular risk factor? Evidence from population
      based studies.
AB  - The question on whether menopause is an independent cardiovascular risk factor is
      still under debate. The results of four studies conducted by our staff in North
      East Italy, including > 11,000 subjects from the general population and covering
      a range of ages from 18 to 95 years, have been employed. We found apparently
      higher blood pressure (BP) values in naturally menopausal than in fertile women,
      but this difference disappeared after age-correction, or after identifying
      fertile and menopausal age-matched women. Significantly higher levels of serum
      lipids were also observed in menopausal than in fertile women but, in this case
      too, any difference disappeared after age-correction/matching. In a 16-year
      longitudinal analysis we found that BP increase and incidence of hypertension
      were the same in the women who remained fertile, in those becoming naturally
      menopausal and in those already menopausal at baseline; going through the
      menopause period, therefore, has no effect on BP. A mild and transitory BP
      increase was only observed during the climacterium. The BP increase during a
      follow-up and the incidence of new cases of hypertension were also similar in the
      women who remained fertile and in those who underwent bilateral ovariectomy,
      indicating no direct effect on BP for surgical menopause. In contrast, vectorial
      analysis demonstrated an excess increment of serum lipids among the women who
      underwent oophorectomy. In our populations, menopause had no predictive role and
      was rejected from the multivariate equations of risk, cardiovascular risk being
      completely explained by age and BP (both higher in menopausal then in fertile
      women).

PMID- 12183845
TI  - Hypertension and diabetes in women.
AB  - Arterial hypertension and diabetes mellitus are two important and frequent risk
      factors for atherosclerosis and their association in the same patients is
      particularly elevated, suggesting something more than the simple causality due to
      their frequency. In women with diabetes mellitus, the risk of cardiovascular
      complications is similar to that in men with diabetes mellitus, a pattern
      completely different from that in the general population where the cardiovascular
      risk in women is significantly lower than in men. During the gestational period,
      the glucose metabolism may be reduced and there may be an elevation of blood
      pressure with or without proteinuria and both conditions have a negative
      prognostic impact for the mother and for the fetus. On the contrary, reduced
      glucose tolerance during pregnancy does not seem to represent an important risk
      factor. The advent of ambulatory blood pressure monitoring has allowed one to
      evaluate in more detail the pattern of blood pressure in normal pregnancy or
      pregnancy complicated by diabetes mellitus or hypertension.

PMID- 12183846
TI  - Hypertension and obesity after the menopause.
AB  - It is well known that in pre-menopausal women the incidence of cardiovascular
      events is lower than in men of the same age and that after the menopause
      cardiovascular morbidity and mortality in women become similar, if not higher,
      than that in men indicating that female sex hormones play a relevant protective
      role upon the vasculature. Among the cardiovascular risk factors, hypertension
      appears to be more prevalent in postmenopausal women than in men but the precise
      mechanism through which menopause favours the development of hypertension is
      still a matter of debate. The prevalence of obesity and being overweight is also
      higher in postmenopausal women than that in men of comparable age. The
      pathogenesis of obesity-related hypertension recognizes a multifactorial
      mechanism including overactivity of the sympathetic nervous system, insulin
      resistance, leptin resistance, overactivity of the renin-angiotensin-aldosterone
      system and, finally, a blunted biological activity of the natriuretic peptides.
      The latter mechanism has been investigated by our group in recent years. Adipose
      tissue has been shown to express large amounts of mRNA for the biologically
      inactive C-type natriuretic peptide receptor (NPr-C) and this expression is
      decreased by fasting. Accordingly, adipose tissue can participate in the
      development and maintenance of high blood pressure through a reduced
      bioavailability of circulating natriuretic peptides leading to sodium retention.
      Since being overweight and obesity are a common finding in postmenopausal women,
      the complex mechanism of obesity-related hypertension can play a relevant role in
      explaining the high prevalence of hypertension after the menopause.

PMID- 12183847
TI  - Hypertensive disease and pregnancy.
AB  - Uniformity in diagnosis and classification of hypertension in pregnancy is
      important for management, comparing investigative reports, as well as future
      prognosis; generally it is diagnosed by diastolic blood pressure > or = 90 mmHg,
      and/or systolic > or = 140 mmHg. Precise etiology remains elusive, but
      investigations have revealed that abnormal placentation, endothelial dysfunction,
      abnormalities in maternal circulatory adaptations to pregnancy, genetic factors
      and immunologic agents all play a role in development of the disease. Trials to
      evaluate various agents to prevent pre-eclampsia have been disappointing, with
      minimal evidence that aspirin, calcium, or vitamins C or E prevent disease, and
      no evidence that antihypertensive agents or diuretics do so. Management of the
      hypertensive gravida is designed to prevent maternal and perinatal morbidity and
      mortality, including more intense antepartum surveillance, as well as intrapartum
      magnesium sulfate to prevent seizures, antihypertensive agents (e.g. hydralazine,
      beta-blockers) to control blood pressure, and continuous fetal monitoring.
      Prognosis in future gestations is dependent upon timing of the disease in the
      index pregnancy, severity and classification of the disease.

PMID- 12183848
TI  - Definition and epidemiology of hypertensive cardiovascular disease in women: the
      size of the problem.
AB  - There remains a gap in our appreciation of gender differences that relate to the
      epidemiology of hypertensive cardiovascular disease. More women than men have
      hypertension. Cardiovascular disease, particularly coronary heart disease, is the
      leading cause of death in women in the industrialized countries of the world. The
      so-called female protection from coronary heart disease pertains primarily to
      young women. Indeed, there are risk factors such as diabetes that eliminate any
      gender advantage that women have over cardiovascular disease. There are also
      major gender differences in the clinical presentation of coronary heart disease.
      Women, until recently, have been under-represented in clinical trials, raising
      concerns as to the applicability of current guidelines for the diagnosis and
      treatment of hypertensive cardiovascular disease. This short review will
      highlight gender differences and similarities as noted in recent observational
      studies and intervention trials.

PMID- 12183849
TI  - Left ventricular hypertrophy and heart failure in women.
AB  - The importance of left ventricular hypertrophy (LVH) as a powerful predictor of
      cardiovascular morbidity and mortality, independent from blood pressure and other
      cardiovascular risk factors, is widely recognized. Women have a lower prevalence
      of LVH than men for any given level of blood pressure. The occurrence of LVH
      increases progressively with older age and LVH becomes more common in women after
      menopause. Available data indicate that both hypertension and LVH are stronger
      risk factors for stroke and for heart failure in women than in men. Women are
      more likely to maintain a better left ventricular systolic function than men with
      similar heart failure symptoms, and heart failure due to diastolic dysfunction is
      more common in women than in men. Few studies have demonstrated that patients who
      fail to achieve a reduction of LVH are much more likely to suffer cardiovascular
      events than those in whom the left ventricular mass is reduced by
      antihypertensive treatment. Reversal of LVH therefore represents a major goal in
      the treatment of hypertensive patients. The degree of cardiac hypertrophy
      reduction is influenced by baseline severity of LVH, by the duration of treatment
      and by the degree of 24-h blood pressure control. In addition, beyond the control
      of blood pressure, different classes of antihypertensive drugs may differently
      interfere with several non-hemodynamic stimuli, and therefore have a different
      effect on left ventricular mass. Data regarding the effect of antihypertensive
      therapy on LVH in women are not adequate. Few studies have suggested a possible
      additive effect of estrogen replacement therapy on left ventricular mass changes
      in hypertensive postmenopausal women. Many of the major heart failure
      intervention trials did not include women or had only a small proportion of
      female patients. In the SAVE, AIRE, TRACE and SOLVD trials, treatment with
      angiotensin-converting enzyme inhibitors resulted in similar benefit to women and
      in men. In studies evaluating the effect of beta-blocker treatment in patients
      with heart failure, the benefit was statistically significant in men but not in
      women. Results from further multicenter ongoing trials are awaited to definitely
      evaluate whether regression of LVH carries a similar benefit in women and men,
      and whether different therapeutic strategies may be applied to women to regress
      LVH and to prevent the progression to heart failure.

PMID- 12183850
TI  - Cerebrovascular disease in women.
AB  - Stroke represents a severe and growing health problem in the general population.
      The increasing burden of disease associated with stroke appears to be largely
      related to progressive ageing of the population, and in fact is increasing more
      rapidly in women than in men. In addition, emerging pathophysiological, clinical
      and therapeutic issues confer specific characteristics to stroke in women. This
      article briefly covers some of the most important of these aspects.

PMID- 12183851
TI  - Treating hypertension in women: open-ended questions and therapeutic options.
AB  - Early intervention studies have challenged the notion that lowering blood
      pressure is beneficial in women with mild hypertension. In contrast, results of
      more recent trials have clearly shown that treatment of hypertension is of
      benefit in women, particularly in elderly women. Aggressive treatment of
      hypertension is advisable in this subset of the population that is exposed to a
      greater risk of hypertension-related cardiovascular diseases because of the
      greater prevalence of hypertension and of its inadequate treatment. Hypertensive
      women are preferentially treated with diuretics but the rationale for this
      therapeutic selection is unclear. Calcium antagonists, beta-blockers and
      angiotensin-converting enzyme inhibitors exert an antihypertensive action similar
      to that of diuretics, but their use is limited by the adverse effects that are
      more frequent in women than in men. Angiotensin II receptor antagonists, being
      effective in lowering blood pressure and particularly well tolerated, may
      represent, in the future, the first-line drugs for treating hypertension in
      women.

PMID- 12183852
TI  - Evidence-based medicine and treatment of hypertension in women: results of
      trials.
AB  - PURPOSE: The aim of this review is to summarize the evidence from randomized
      controlled trials and meta-analyses of hypertension treatment trials that
      included women in their study population and subsequent analyses. RESULTS: Most
      early hypertension treatment trials did not include women in their study
      population, or did so in insufficient numbers to assess gender-specific outcomes.
      Women, particularly the elderly, were better represented in subsequent studies,
      but gender-specific results were not often reported and most trials were not
      designed or powered to detect gender differences in treatment responses and
      outcomes. In some studies where gender-specific results have been reported,
      gender differences have been observed, but the direction of the effect has
      generally been similar in men and women. Large meta-analyses of treatment trials
      have found similar relative risk reductions as a result of hypertension
      treatment, but lower absolute risk reductions in women compared to men. Absolute
      risk reductions are strongly related to baseline risk and have been demonstrated
      in virtually all subgroups of women except those with extremely low aggregate
      cardiovascular risk. While there are still limited data regarding treatment
      benefits for young women, no subset of women has been shown to experience net
      harm as a result of hypertension therapy. CONCLUSION: The design and
      implementation of future hypertension treatment trials should include the
      provision to assess gender-specific differences in treatment and outcomes.

PMID- 12183853
TI  - The treatment of hypertension in pregnancy.
AB  - The hypertensive disease that occurs during pregnancy is a multifaceted clinical
      condition whose accurate diagnosis, not limited to the evaluation of degree of
      the hypertensive derangement, is crucial for a correct therapeutic approach. In
      particular, chronic hypertension pre-existing before pregnancy should be clearly
      differentiated from the hypertensive disease induced by pregnancy and
      particularly from pre-eclampsia. Non-pharmacological measures of intervention
      have not been proven to improve both maternal and fetal outcome. Severe
      hypertension during pregnancy (blood pressure > 170/110 mmHg) should be
      immediately treated with drugs that have been proven to prolong pregnancy and to
      improve both maternal and fetal outcome. In patients with mild to moderate
      hypertension, both chronic and pregnancy induced, antihypertensive treatment
      improves the maternal outcome, whereas no clear-cut evidence of benefit have been
      reported at the fetal level. Among the different antihypertensive drugs that have
      been reported to be effective, safe and well tolerated during pregnancy,
      methyldopa, beta-blockers and particularly calcium channel blockers (nifedipine)
      represent the more suitable solution.

PMID- 12183854
TI  - Non-pharmacological treatment of hypertension in women.
AB  - This paper reviews literature data about non-pharmacological treatment of
      hypertension in women. A reduction in salt intake, an increase in physical
      activity and body weight reduction have been clearly demonstrated to be effective
      in reducing blood pressure values in women. Other lifestyle changes have been
      investigated in past years, but the results are still debated. A 4-8% body weight
      reduction causes an average 3 mmHg blood pressure decrease. However, many women
      tend to regain the weight (weight cycling), and in this case an increase of blood
      pressure can be observed. Older women are less responsive to low-calorie diets.
      Sodium restriction is effective in a dose-dependent way. The main problem is that
      good compliance is difficult to obtain. Salt substitutes may be helpful. Regular
      physical activity can reduce blood pressure by at least 5/3 mmHg, while walking
      for less than 2 h per week can reduce the risk of stroke by 50%. Data on coffee
      drinking are less conclusive even if there is evidence that the effect on blood
      pressure is greater at increasing levels of blood pressure. The reduction of
      alcohol intake, an increase in fibers and an increase in unsaturated fatty acids
      are well known tools to improve blood pressure control. Within unsaturated fatty
      acids, olive oil seems to be particularly helpful since it is able to produce
      significant blood pressure reductions, which are greater than those observed with
      sunflower oil.

PMID- 12183855
TI  - Pathophysiological aspects of hypertensive disease in women.
AB  - Although during the past two decades there has been considerable progress in the
      understanding of the pathophysiology of human essential hypertension, the basic
      mechanisms responsible for the development and progression of the disease still
      remain largely undefined. This also applies to the pathophysiology of
      hypertension in women, although a number of haemodynamic, vascular, metabolic and
      neurohumoral factors have been identified throughout the years as being
      characterized by a gender-specific relation. This paper will examine the main
      differences in the haemodynamic, vascular, metabolic and neurohumoral profile
      characterizing normotensive as well as hypertensive females as compared with age
      matched males. Although in some instances clearcut differences between genders
      can be found, overall the pathophysiological picture of the hypertensive state
      does not seem to have significant differences in men and women, at least up to
      the years when the menopausal-related hormonal changes take place.

PMID- 12183856
TI  - Effect of postmenopausal hormone therapy on cardiovascular risk.
AB  - The role of postmenopausal hormone therapy for the prevention and treatment of
      coronary heart disease remains an important unanswered question. Clinical trials
      have not yet produced evidence of benefit, and at least one trial has suggested
      initial harm after initiation of therapy. The data from observational
      epidemiology remain supportive of benefit, however these data are subject to
      various biases and interpretations. Mechanistic studies support either potential
      benefit or potential harm. Postmenopausal hormone therapy should not be
      recommended for the prevention of coronary heart disease until the potential
      early harm has been explained, methods of screening out women at high risk have
      been devised, and long-term benefit has been demonstrated in randomized
      controlled clinical trials.

PMID- 12183857
TI  - A comprehensive approach to target organ damage in hypertensive women.
AB  - PURPOSE: The aim of the present study was to demonstrate how the regression of
      target organ damage (TOD) in patients with hypertension really improves
      prognosis. This issue has already been demonstrated in the general population but
      no data have been provided in postmenopausal women, which represents a particular
      group of high-risk hypertensive patients. STUDY SELECTION: We initially chose to
      select a number of studies focused on the regression of left ventricular
      hypertrophy since this plays an extremely important prognostic role and is among
      the restricted number of risk factors that may be corrected with adequate
      treatment. We also focused our attention on the issue of endothelial dysfunction,
      considering that this relatively new pathophysiological entity may represent
      sensu strictu real organ damage of hypertension that has often been demonstrated
      in postmenopausal women. RESULTS OF DATA ANALYSIS: All the reviewed studies agree
      that the regression of left ventricular hypertrophy is a positive prognostic
      factor. Moreover, antihypertensive therapy itself is associated with some changes
      in the degree of endothelial dysfunction. Our preliminary data seem to suggest
      that the regression of endothelial dysfunction plays a very important prognostic
      role in terms of event reduction in postmenopausal patients with hypertension.
      CONCLUSION: Despite a large amount of research remaining to be carried out on the
      mechanism and the prognostic role of the modifications of TOD in patients with
      hypertension, the available data demonstrate that the achievement of a reduction
      in the extent of TOD is extremely important for the evaluation of the efficacy of
      the treatment in the general hypertensive population, and also in postmenopausal
      women.

PMID- 12183858
TI  - Use of statin drugs in women.
AB  - Risk factors associated with the progression of coronary disease are the same in
      women and men, although there are some quantitative differences. Diabetic women,
      for example, are exquisitely sensitive to the development of atherosclerosis.
      There is no clinical trial devoted to the study of cholesterol lowering in women.
      A meta-analysis of recent statin trials with clinical endpoints, however,
      demonstrates that cholesterol lowering is as beneficial in women as it is in men.
      Hormone replacement therapy has not been demonstrated in a clinical trial to be
      of benefit, even though there is considerable observational, epidemiology and
      basic science evidence that indicates that it might be. It is important that the
      risk of coronary disease and stroke, particularly in older women, be recognized.
      Patients at risk should receive cholesterol-lowering treatment with statin drugs
      to prevent both atherosclerotic morbidity and mortality.

PMID- 12183859
TI  - Treating relapsed epithelial ovarian cancer with luteinizing hormone-releasing
      agonist (goserelin) after failure of chemotherapy.
AB  - BACKGROUND: The treatment of patients with recurrent ovarian carcinoma after
      failure of first and second-line chemotherapy is still debated. Chemical agents
      used for third and fourth-line therapy usually yield poor results with severe
      toxic side effects. OBJECTIVE: To summarize our experience with goserelin in the
      treatment of patients with recurrent ovarian cancer. METHODS: From September 1996
      to June 1999 we administered goserelin, 3.6 mg subcutaneously every 4 weeks, to
      15 patients with advanced and recurrent epithelial ovarian cancer (median age
      59.0, median performance status 3.0). RESULTS: Seven of 15 eligible patients
      relapsed after platinum-based chemotherapy (3 of them also received paclitaxel
      and another 2 received tamoxifen). Four patients relapsed after carboplatin and
      paclitaxel, one of whom was treated with topotecan thereafter. Two patients
      relapsed after single-agent paclitaxel. Two patients with advanced disease and
      poor performance status without previous treatment received only goserelin. There
      was one complete response (6.7%) and 1 partial response (6.7%) lasting 8 and 14
      months respectively (overall response rate 13.4%). In addition, the disease
      stabilized in three patients (20%) for a median of 7.5 months. In 10 patients the
      disease progressed. There was no significant toxicity. Median survival of all
      patients was 5.8 months. CONCLUSION: Goserelin was helpful in one-third of our
      patients with advanced and refractory ovarian cancer. It is an easy and non-toxic
      option for treating very ill or previously heavily treated patients.

PMID- 12183860
TI  - Balloon angioplasty versus bypass grafting in the era of coronary stenting.
AB  - BACKGROUND: Patients with multivessel coronary artery disease are candidates for
      either angioplasty and stenting or coronary artery bypass grafting. A prospective
      randomized study designed to compare the both methods included only a minority of
      the eligible patients. OBJECTIVE: To compare coronary artery bypass grafting to
      angioplasty plus stenting in patients with multivessel disease who declined
      randomization to a multicenter study (the ARTS). METHODS: During 1997-98 we
      prospectively followed 96 consecutive patients who were eligible according to the
      ARTS criteria but refused randomization. Of these patients, 50 underwent
      angioplasty + stenting and 46 underwent coronary bypass surgery. We compared the
      incidence of major adverse cardiac and cerebral events, chest pain recurrence,
      quality of life and procedural cost during the first 6 months. RESULTS: All
      procedures were completed successfully without mortality or cerebral events. The
      rate of Q-wave myocardial infarction was 2% in the AS group vs. 0% in the CABG
      group (not significant). Minor complications occurred in 7 patients (14%) in the
      AS group and in 21 patients (45%) in the CABG group (P < 0.01). At 6 months
      follow-up the incidence of major cardiac and cerebral events was similar in both
      groups (11% and 4% in the AS and CABG groups respectively, P = NS). Seventeen
      patients (36%) in the AS group required repeat revascularization compared to only
      3 (7%) in the CABG group (P = 0.002). Nevertheless, quality of life was better,
      hospitalization was shorter and the cost was lower during the first 6 months
      after angioplasty. CONCLUSION: Angioplasty with stenting compared to coronary
      bypass surgery in patients with multivessel disease resulted in similar short
      term major complications. However, 36% of patients undergoing angioplasty may
      need further revascularization procedures during the first 6 months.

PMID- 12183861
TI  - Low plasma antioxidants and normal plasma B vitamins and homocysteine in patients
      with severe obesity.
AB  - BACKGROUND: Obesity is among the well-established risk factors for cardiovascular
      morbidity and mortality. However, the exact mechanisms are not well understood.
      Low concentrations of vitamins (fat soluble antioxidants and B vitamins) are
      linked to accelerated atherosclerosis through increased oxidative stress and
      homocysteine. OBJECTIVE: To compare plasma antioxidant vitamins (carotenoids and
      vitamin E), B vitamins (folic acid and B12) and homocysteine--all linked to
      increased cardiovascular morbidity--between patients with severe obesity and lean
      control subjects. METHODS: We investigated plasma carotenoids, vitamin E, folic
      acid, B12, and homocysteine in 25 obese patients and their age-matched controls
      (body mass index 38 +/- 3 vs. 21 +/- 2 kg/m2), respectively), related to BMI and
      plasma insulin. RESULTS: Patients with obesity had normal B vitamins and a non
      significant decrease in plasma homocysteine as compared to controls (9.4 +/- 2.6
      vs. 11.4 +/- 4.8 mumol/L, P = 0.07). There was a significant decrease in both
      plasma carotenoids and vitamin E (0.69 +/- 0.32 vs. 1.25 +/- 0.72 and 24 +/- 10
      vs. 33 +/- 14 micrograms/ml, respectively; P < 0.01). Both vitamins were
      inversely related to BMI and plasma insulin, which was significantly increased in
      patients with obesity (22 +/- 21 vs. 6 +/- 2 microU/ml, P < 0.01). CONCLUSIONS:
      Obese patients with BMI above 35 kg/m2 show low plasma antioxidants (carotenoids
      and vitamin E). This may result in increased oxidative stress and consequently
      enhanced atherosclerosis in these patients.

PMID- 12183862
TI  - ELISA of anti-endomysial antibodies in the diagnosis of celiac disease:
      comparison with immunofluorescence assay of anti-endomysial antibodies and tissue
      transglutaminase antibodies.
AB  - BACKGROUND: Celiac disease is common in both children and adults. Small
      intestinal biopsy is mandatory for establishing a diagnosis. Anti-endomysial
      antibodies, detected by immunofluorescence, have a sensitivity and specificity
      close to 100% in the diagnosis of CD. Recently, tissue transglutaminase has been
      identified as the target autoantigen of antibodies against endomysium, and TTG
      antibodies are comparable to EMA-IMF in the diagnosis of CD. OBJECTIVE: To
      evaluate a new enzyme-linked immunosorbent assay kit for EMA, compared to EMA-IMF
      and TTG antibodies in the diagnosis of CD. METHODS: Our study population included
      all subjects with positive EMA-IMF who underwent intestinal biopsy (n = 21). From
      the same sera, TTG antibodies and EMA-ELISA were determined, and all antibody
      results were compared to the biopsy findings. RESULTS: EMA-IMF was able to
      predict biopsy findings of CD in 19 of 21 cases (90.5%). When patients with
      biopsy findings compatible with CD and positive EMA-IMF (n = 19) were tested for
      EMA-ELISA and TTG antibodies, 18 of the 19 were positive for both EMA-ELISA and
      TTG antibodies. A significant correlation was found between EMA-ELISA and TTG
      antibody titers (r = 0.74, P < 0.001). CONCLUSIONS: Our study demonstrates that
      EMA-ELISA is comparable to TTG antibodies in the diagnosis of CD, and supports
      the use of EMA-ELISA as a serologic marker for this disease.

PMID- 12183863
TI  - Reconstruction of the mandible by fibula free flap.
AB  - BACKGROUND: The most frequent cause of defect in the mandible is tumor-related
      surgery. Larger defects or anterior arch defects cause severe morbidity due to
      disturbances in function and esthetics. OBJECTIVES: To assess the outcome of free
      tissue transfer for mandible reconstruction. METHODS: Since 1998 we operated on
      11 patients with mandible defects using the fibula flap as the reconstruction
      method. We performed immediate reconstruction in eight patients after ablative
      surgery, and late reconstruction due to radiation-induced complications in three.
      RESULTS: All patients achieved good functional and esthetic outcome. During the
      follow-up period two patients died of their malignant disease and one patient
      died from a non-related cause. Although two patients underwent reoperation in the
      first 3 months after their primary operation due to fixation failure, there were
      no other major complications. CONCLUSIONS: According to the literature and our
      limited experience, the fibula flap is a safe and reliable option for mandible
      reconstruction.

PMID- 12183864
TI  - Predictors of patient dissatisfaction with emergency care.
AB  - BACKGROUND: Patient feedback is increasingly being used to assess the quality of
      healthcare. OBJECTIVE: To identify modifiable independent determinants of
      patients dissatisfaction with hospital emergency care. METHODS: The study group
      comprised a random sample of 3,152 of the 65,966 adult Israeli citizens
      discharged during November 1999 from emergency departments in 17 of the 32 acute
      care hospitals in Israel. A total of 2,543 (81%) responded to a telephone survey
      that used a structured questionnaire. The dependent variables included: hospital
      characteristics, patient demographic variables, patient perception of care, self
      rated health status, problem severity, and outcome of care. The dependent
      variable was dissatisfaction with overall ED experience on a 1-5 Likert-type
      scale dichotomized into not satisfied (4 and 5) and satisfied (1, 2 and 3).
      RESULTS: Eleven percent of the population reported being dissatisfied with their
      emergency room visit. Univariate analyses revealed that dissatisfaction was
      significantly related to ethnic group, patient education, hospital identity and
      geographic location, perceived comfort of ED facilities, registration expediency,
      waiting times, perceived competence and attitudes of caregivers, explanations
      provided, self-rated health status, and resolution of the problem that led to
      referral to the ED. Multivariate analyses using logistic regressions indicated
      that the four most powerful predictors of dissatisfaction were patient perception
      of doctor competence and attitudes, outcomes of care, ethnicity, and self-rated
      health status. CONCLUSIONS: Attempts to reduce dissatisfaction with emergency
      care should focus on caregiver conduct and attitudes. It may also be useful to
      improve caregiver communication skills, specifically with ethnic minorities and
      with patients who rate their health status as poor.

PMID- 12183865
TI  - Ghrelin: much more than a natural growth hormone secretagogue.
AB  - Ghrelin, a 28 amino acid acylated peptide predominantly produced by the stomach,
      displays strong growth hormone-releasing activity mediated by the hypothalamus
      pituitary GH secretagogue receptors that were found to be specific for a family
      of synthetic, orally active GH secretagogues. The discovery of ghrelin brings us
      to a new understanding of the regulation of GH secretion. However, ghrelin is
      much more than simply a natural GH secretagogue. It also acts on other central
      and peripheral receptors and exhibits other actions, including stimulation of
      lactotroph and corticotroph secretion, orexigenic, influences
      gastroenteropancreatic functions, and has metabolic, cardiovascular and
      antiproliferative effects. Knowledge of the whole spectrum of biologic activities
      of this new hormone will provide new understanding of some critical aspects of
      neuroscience, metabolism and internal medicine. In fact, GHS were born more than
      20 years ago as synthetic molecules, eliciting the hope that orally active GHS
      could be used to treat GH deficiency as an alternative to recombinant human GH.
      However, the dream did not become reality and the usefulness of GHS as an
      anabolic anti-aging intervention restoring the GH/IGF-I axis in somatopause is
      still unclear. Instead, we now face the theoretic possibility that GHS analogues
      acting as agonists or antagonists could become candidate drugs for the treatment
      of pathophysiologic conditions in internal medicine totally unrelated to
      disorders of GH secretion.

PMID- 12183866
TI  - Vascular involvement in Behcet's disease.

PMID- 12183867
TI  - Suspected child abuse and neglect: assessment in a hospital setting.

PMID- 12183868
TI  - Arterial revascularization versus metal stents for multivessel diseases: a
      shifting frontier.

PMID- 12183869
TI  - Serum anti-endomysial and anti-tissue transglutaminase for screening of celiac
      disease.

PMID- 12183870
TI  - Reconstruction of the mandible by fibula free flap.

PMID- 12183871
TI  - Vibrio Vulnificus infections can be avoided.

PMID- 12183872
TI  - The ATP site of protein kinases as target for drug development: from natural
      compounds to gleevec.

PMID- 12183873
TI  - Vasculo-Behcet's disease.

PMID- 12183874
TI  - Molecular medicine--an overview.
AB  - Advances in the fields of molecular genetics and cell biology are transforming
      medicine. Discoveries made today in the laboratory are translated at a rapid pace
      into new diagnostics and therapeutics. The aim of this series of review on
      different aspects of molecular medicine is to update physicians on new advances
      at the bench that are likely to impact bedside medicine.

PMID- 12183875
TI  - The mitogen-activated protein kinase signaling cascade: from bench to bedside.

PMID- 12183876
TI  - Stem-cell transplantation for primary immunodeficiencies.
AB  - Until further improvement in gene therapy is achieved, stem-cell transplantation
      is still the main option for cure of patients with primary immunodeficiency
      diseases. Performing the transplant in early infancy before severe infections and
      organ damage develop has the highest chance for success. The remarkable progress
      that has been achieved in understanding these disorders has made it possible to
      identify most of the genetic abnormalities. This enables an early transplant
      immediately after birth or even in utero. However, the optimal approach for stem
      cell transplantation in children with immunodeficiency has yet to be determined.
      The non-myeloablative protocols increasingly used in recent years have the
      potential for immune reconstitution without considerable toxicity, but the
      experience is still limited. A better understanding of the specific immune
      dysfunction and the exact degree of residual immunity may enable the tailoring of
      the most appropriate conditioning regimen for each patient so that engraftment
      will be ensured with little morbidity.

PMID- 12183877
TI  - Hemoclip placement as definitive therapy for bleeding from a dieulafoy lesion.

PMID- 12183878
TI  - Fulminant wound infections due to vibrio vulnificus.

PMID- 12183879
TI  - Central pontine myelinolysis after alcohol withdrawal.

PMID- 12183880
TI  - Staphylococcal parotitis in a neonate.

PMID- 12183881
TI  - Torsion of a wandering spleen.

PMID- 12183882
TI  - Pseudo-tumor of the caudate lobe in primary sclerosing cholangitis.

PMID- 12183884
TI  - Pest control.

PMID- 12183883
TI  - Bronchial asthma in Israel.
AB  - Asthma in Israel is a growing medical problem, affecting at least 7% of children
      and 3.7% of the total population. Mortality rates in the age group 5-34 years
      were on a rise between 1976 and 1990 but show a marked decrease in recent years,
      perhaps due to the sharp increase in sales of inhaled corticosteroids. There is
      also a recent indication that the relatively high crude mortality rate among
      women is declining (from 3.68 and 4.58 per 100,000 population in 1995 and 1996
      respectively, to 3.58 per 100,000 in 1997). In spite of better asthma education
      and management there is still a gap between available medical knowledge and
      medical therapy and its utilization for the benefit of the asthmatic population
      in Israel.

PMID- 12183885
TI  - Immigration and CAD risk factors.

PMID- 12183886
TI  - Cohabitation, marriage, divorce, and remarriage in the United States.
AB  - OBJECTIVES: This report presents national estimates of the probabilities of
      marital and cohabitation outcomes for women 15-44 years of age in 1995, by a wide
      variety of individual- and community-level characteristics. The life-table
      analysis in this report takes a life cycle approach to estimate the probabilities
      that: a woman will marry for the first time, an intact first cohabitation will
      make the transition to marriage, a first cohabitation will end in separation, a
      first marriage will end in separation or divorce, a disrupted first marriage will
      be followed by a new cohabitation, a separation from first marriage will result
      in divorce, a divorce from first marriage will be followed by remarriage, and a
      second marriage will end in separation or divorce. METHODS: The life-table
      estimates presented here are based on a nationally representative sample of women
      15-44 years of age in the United States in 1995 from the National Survey of
      Family Growth, Cycle 5. RESULTS: The analyses show that various individual and
      community-level characteristics are related to the marital and cohabitational
      outcomes examined in this report. The results consistently demonstrate that the
      cohabitations and marriages of non-Hispanic black women are less stable than
      those of non-Hispanic white women. An analysis of trends over time suggests that
      differences by race/ethnicity are becoming more pronounced in recent years.
      Racial differences observed are associated with individual characteristics and
      with the characteristics of the communities in which the women live.

PMID- 12183887
TI  - [Risk of drug interactions. Combinations of drugs associated with ventricular
      arrhythmias].
AB  - OBJECTIVE: To determine the frequency of concurrent use of cisapride, astemizole
      and terfenadine with macrolides and azole antimitotics, drug combinations that
      have been reported in the literature as producing a pharmacological interaction
      associated with potentially fatal ventricular arrhythmias. MATERIAL AND METHODS:
      A retrospective analysis of a total of 72,444 prescriptions generated by 611
      physicians during a 6 months period for ambulatory patients, was performed. The
      database included a register of automatic alerts produced every time a
      predetermined drug combination was detected. RESULTS: 145 potentially risk
      situations were detected, with an incidence rate to 2.1 cases per 1,000
      prescriptions, which increases to 6.2% when prescriptions for terfenadine,
      astemizole, and cisapride were included, with 12, 9 y 5%, respectively. Only 36
      physicians (6%) wrote prescriptions producing alerts, and about half (45%) were
      pediatricians. The same physician prescribed both drugs in 31% of the cases.
      CONCLUSION: The use of drug combinations associated with a high risk of
      potentially fatal ventricular arrhythmias is relatively high in Mexico. An
      electronic online detecting system showed to be useful in preventing this kind of
      potential pharmacological interactions.

PMID- 12183888
TI  - [Effectiveness of preemptive therapy with ganciclovir in recipients of renal
      transplants at high risk (R-/D+) for the development of cytomegalovirus disease].
AB  - Current management of renal transplant recipients who are CMV seronegative (R-)
      and receive an organ from a seropositive donor (D+) is controversial. These
      patients are at high risk for CMV disease and are usually treated with
      ganciclovir prophylaxis at variable dose and duration. An alternative to this
      approach is to administer ganciclovir only to those patients who are identified
      by virological markers to be at the highest risk to develop the disease
      (preemptive therapy). This prospective trial was conducted to asses the value of
      preemptive therapy to prevent CMV disease in R-/D+ kidney transplant recipients
      on triple drug immunosuppression without antilymphocyte induction. Sixteen adults
      receiving their first kidney transplant were enrolled and followed with pp65
      antigenemia assay performed biweekly for the first 16 postransplant weeks, and
      then monthly to complete 12 months. Ganciclovir (5 mg/kg/day i.v., for 15 days)
      was administered as preemptive therapy upon detection of one or more antigen
      positive cells per 150 x 10(3) peripheral blood leucocytes examined. For those
      receiving preemptive therapy, pp65 antigenemia was also repeated after completion
      of the regimen. CMV antigenemia was detected in 7/16 patients. At mean follow-up
      of 9 months (4-12 m) none of the 16 patients developed CMV disease. CMV serology
      (IgM) became positive in all patients after the first antigenemia result. The
      last follow-up mean serum creatinine (SCr) level was similar in both groups (1.35
      mg/dL). In CMV R-/D+, the use of preemptive therapy guided by pp65 antigenemia is
      effective in preventing CMV disease. By using this strategy, 9 of 16 patients
      were spared ganciclovir prophylaxis with no effect on rejection or CMV disease.
      The clinical benefit and cost/effectiveness of this strategy should be evaluated
      against universal prophylaxis in these high-risk patients.

PMID- 12183889
TI  - Occult breast carcinoma presenting with axillary lymph node metastases.
AB  - BACKGROUND AND OBJECTIVES: Occult primary breast carcinoma is uncommon. Most
      reported series encompass a large periods of time with great variability in
      diagnostic and treatment approaches. The objective of the present study was to
      review the recent experience with this type of presentation of breast cancer in
      the University of Alabama at Birmingham. METHODS: Retrospective review of
      clinicopathological data of female patients presenting with axillary metastasis
      of adenocarcinoma with unknown primary and normal clinical and mammographic
      breast exam seen at UAB between 1985 and 1998. RESULTS: Ten patients were
      identified. Mean age was 56 years. Sixty per cent were white and postmenopausal.
      All patients had biopsy proven adenocarcinoma consistent with breast primary. All
      but one patient underwent an axillary dissection. Nine out of ten patients
      received some type of local treatment to the breast. Three of them underwent
      mastectomy and no invasive carcinoma was demonstrated in the surgical specimens.
      Six patients received radiation therapy to the breast. All patients received
      chemotherapy. With mean follow-up time of 48 months, two patients developed local
      recurrence to the axilla and four developed distant metastasis and eventually
      died. At last follow-up six patients are alive with no evidence of disease.
      CONCLUSIONS: In presence of axillary metastasis from an unknown breast primary,
      an extensive work-up evaluation is not necessary. An axillary dissection is
      recommended to provide prognostic indicators as well as local control. A breast
      conservation approach seems to be feasible without affect the local control and
      survival.

PMID- 12183890
TI  - [Rasnmussen syndrome. 7 years' follow-up. Aspects related to cerebral plasticity
      in epilepsy].
AB  - Present study represents a case follow up for seven years. A case of Epilepsy
      Partialis Continua (EPC) in a fifteen year old girl was studied with CT, MRI,
      cerebral SPECT and constantly EEG procedures: The SPECT study showed in right
      frontal lobe and right temporal lobe hypoperfusion (reduction of regional
      cerebral blood flow [rCBF]) cerebral zone in the interictal period and
      hyperperfusion (increase rCBF) in the ictal period in the same hemisphere. The
      EEG showed abnormal activity consisting in sharp wave and polyphasic sharp wave
      in frontal and temporal regions. The medical treatment was refractory at all kind
      of anticonvulsant drugs. In order to improve the refractory epilepsy the team
      decided an epilepsy surgery with right temporal lobotomy and right frontal
      corticetomy. This procedure were done at the eight year old and the results were
      satisfactory immediately after the surgery with absolute control and normal
      cognitive performance two weeks later the surgery. This patient was follow up for
      seven years with EEG constantly with normal activity, SPECT and MRI, all studies
      showed functional hemispherectomy, total absence in the structure and cerebral
      blood flow in right hemisphere with normal perfusion and structure in left
      hemisphere. The late control of neuropsychology assessment showed some deficits
      in the I.Q. cognitive performance, evaluated by the Weschler scale and Machover
      tests. These findings would be able to demonstrate a phenomenon of brain
      plasticity and neuronal restoration in the left cerebral hemisphere after to
      remove the abnormal cerebral epilepsy focus. This procedure might permits the
      restoration of inadequate neuronal environment and normalization of neural
      physiological stability. The postulated mechanisms of reorganization of function
      are unmasking, nonsynaptic diffusion neurotransmission and receptor plasticity,
      trophic factors, synapsins and neurotransmitters. The neuropsychological
      mechanism to preserve the functions would be involving in a cortical
      reorganization with axonal and dendritic development beside sprouting and
      synaptogenesis. This patient is a good example of neuronal plasticity in epilepsy
      surgery.

PMID- 12183891
TI  - [Effect of metabolic control in type I diabetes patients and its association with
      periodontal disease].
AB  - OBJECTIVE: To compare the frequency of periodontal disease in type 1 diabetes
      mellitus patients with and without metabolic control, having a control group of
      healthy patients. MATERIAL AND METHODS: A prolective cross sectional study with
      simple random sampling was carried out; patients were divided in three groups:
      A). Forty healthy subjects, B). Twenty diabetic patients with metabolic control,
      and C). Twenty diabetic patients without metabolic control. The diabetic subjects
      were evaluated with glycosylated hemoglobin (GHb) to determine the glucose
      control; clinical periodontal evaluations were performed for all teeth in each
      subject and following indexes were included: Plaque, gingival, mobility, probing
      depth, attachment level, bleeding on probing, and marginal bone loss. RESULTS:
      The imbalance of glucose of subjects with diabetes mellitus type 1 was associated
      with more frequency of periodontal disease (p < 0.05). CONCLUSION: The population
      of type 1 diabetes mellitus with imbalance of glucose showed association with
      periodontal disease.

PMID- 12183892
TI  - [The second biennial of the External Quality Evaluation Program in Urinalysis
      (PEECU)].
AB  - OBJECTIVE: To characterize the participation of clinical laboratories in the
      second biennial of an external quality assurance scheme for urinalysis in Mexico.
      METHODS: The participants received 32 control samples in 8 shipments of 4
      controls each during the biennial 1999-2000. The controls were in the form of
      tablets to be dissolved in 12 mL of water to mimic urine. The participants
      performed dipstick assays of pH, specific gravity (SG) and 8 analytes (proteins,
      glucose, ketones, blood, bilirubin, nitrites, urobilinogen, leukocytes) in the
      controls. Expected control values were assigned by 10-15 replicate automated
      assays using dipsticks and apparatus of a single provider (Bayer). Participants'
      results were transformed to scores ranging from zero (perfect result) to 400
      (worst possible). Score differences were analyzed using nonparametric methods
      (Kruskal-Wallis and Mann-Whitney). RESULTS: The best results were seen for
      nitrites, ketones and proteins (mean global scores = 3-5) and the worst for SG
      (score = 45) with intermediate scores of 10-13 for the other six. CONCLUSIONS:
      The scores improved for the second biennial from a grand mean of 17 in the first
      significantly down to 12 in the second. The number of participants has been
      increasing yearly and there has been a decrease of participants who do not report
      at least 3 out of 4 yearly shipments. We confirmed that automated readings yield
      better scores than visual readings.

PMID- 12183893
TI  - [Possible role of transcription factor AP1 in the tissue-specific regulation of
      human papillomavirus].
AB  - Activator protein-1 (AP1) is a dimeric protein, consisting either of homodimers
      between c-Jun, JunB, and JunD of by heterodimers with members of the Fos-family
      by physically interacting via a "leucine zipper" region. AP1 is an important
      transcription factor initially identified as a DNA binding protein that bound to
      enhancer sequences of the human metallothionein IIA gene. The protein components
      of AP1 are encoded by a set of genes known as "immediate-early" genes that can be
      activated by a variety of growth factors and mitogens through several different
      signaling pathways. Until recently, AP1 was considered a transcription factor
      expressed in most tissues to regulate cellular and viral genes now, it is
      becoming evident that AP1 can be involved in tissue-specific regulation of target
      genes due to the differential combination of the components of this important
      transcription factor. AP1 plays a crucial role during human papillomavirus (HPV)
      early gene expression, in particular of the expression of E6 and E7 oncoproteins.
      The HPV are a group of DNA viruses consisting of more than 80 different
      genotypes. Some of these HPV, know as high risk HPV, are important etiologic
      agents of uterine-cervical cancer (CaCu). Of the different types of cancer, CaCu
      is one of the most frequent among women worldwide, constituting the second death
      cause due to neoplasia. During cellular transformation, HPV infect basal cells in
      stratified epithelium; their DNA integrate into the host genome usually through
      the E2 gene; as these cells differentiate and migrate into the upper layer of the
      epithelium, viral oncogene are expressed blocking their differentiation.
      Mutagenesis in AP1 sites belonging to the HPV promoter region (LCR) completely
      abolished the HPV promoter activity in different cell lines; these results and
      biochemistry assays on this AP1 transcription factor, that includes protein
      protein interactions between AP1 and another factors as E7 from HPV, and YY-1;
      the post-translattional modification and, the retinoic acid interaction; suggest
      a role for this AP1 factor in tissue-specific transcription of the human
      papillomavirus.

PMID- 12183894
TI  - [Primary prevention of cerebrovascular disease].

PMID- 12183895
TI  - [Secondary prevention of cerebral ischemia. AMEVASC. Mexican Association of
      Cerebrovascular Disease].

PMID- 12183896
TI  - [General measures and intensive care of acute cerebrovascular accident]].

PMID- 12183897
TI  - [Acute management of cerebral infarction].

PMID- 12183898
TI  - [Atherosclerotic carotid disease and endarterectomy].

PMID- 12183899
TI  - [Diagnosis and treatment of intracerebral hemorrhage].

PMID- 12183901
TI  - [Therapeutic monitoring of cyclosporine A].
AB  - Cyclosporine A (CyA) is a drug with a specific influence on the immune system and
      it is used both to prevent tissue rejection of transplanted organs and to treat
      autoimmune diseases. The properties, metabolism, and methods of therapeutic drug
      monitoring (TDM) in patients under immunosuppressive therapy are described. TDM
      of CyA reflects the clinical condition of the patient during immunosuppression
      and may include pharmacokinetic and pharmacodynamic data obtained either from
      measuring CyA levels in blood, or from determining some other parameters, which
      are modulated by CyA (II-2). Although TDM is mainly based on analyzing trough
      levels of CyA, the determination of the whole biological exposition calculated as
      AUC enables better correlation with the clinical state of patients.
      Pharmacodynamic parameters have not been measured routinely yet.

PMID- 12183900
TI  - [Diagnosis and treatment of subarachnoid hemorrhage].

PMID- 12183902
TI  - [Pharmaceutical importance of Allium sativum L. 3. Antibacterial effects on
      Helicobacter pylori].
AB  - The paper points out the risk factors which render possible the outbreak of
      infections due to the bacterium Helicobacter pylori manifesting itself as chronic
      gastritis. In a great extent it results in peptic and duodenal ulcers and can
      even lead to the development of adenocarcinoma and lymphoma of the stomach. The
      paper mentions the efficacy of previous and contemporary therapy. Possible use of
      garlic in the treatment of these infections is intensively investigated. At
      present mainly in vitro experiments showing promising results are performed. A
      minimum of experiments carried out with out-patients produced negative results.
      As they do not fulfill the parameters of clinical experiments, this question
      still remains open.

PMID- 12183903
TI  - [Ononis arvensis in vitro--abiotic elicitation].
AB  - The effect of two abiotic elicitors--two newly synthesized compounds (substituted
      anilides of pyrazine-2-carboxylic acids)--on the formation of flavonoids in the
      callus culture of Ononis arvensis L. was tested. The compounds markedly
      influenced the production of flavonoids in an in vitro culture. Particularly
      after elicitation with a solution of compound No. 1 (4-hydroxyanilide 6-chloro-5
      terc.butylpyrazine-2-carboxylic acid) in a concentration of 3.32.10(-7) mol.l-1
      and within 48 hours of elicitation an increase in flavonoid formation by 976%
      versus the control took place.

PMID- 12183904
TI  - [Effect of salicylic acid on production of anthracene derivatives in a culture of
      Rheum palmatum L. in vitro].
AB  - Elicitation is a method making use of protective mechanisms of plants to increase
      the production of secondary metabolites in plants and cultures in vitro.
      Salicylic acid acts in plants as an inducer of the expression of protective
      proteins and it can be thus included into biotic elicitors. That is why the
      present paper examined the effects of five concentrations of salicylic acid on
      the production of anthracene derivatives by a three-year and a nine-year old
      culture derived from the root of the intact plant Rheum palmatum L. The culture
      was cultivated on Murashige-Skoog medium with an addition of 10 mg.l-1 of alpha
      naphthylacetic acid. It follows from the results that increase in production
      after elicitation is higher in the three-year old culture than in the nine-year
      old one and elicitation of suspension culture is more successful than elicitation
      of callus culture. The maximal content of anthracene derivatives (1.418%),
      detected by a photometric essay according to PhBS 4, was demonstrated after a 48
      hour action of 1 mM aqueous solution of salicylic acid, when production was
      increased by 101% in comparison with the control.

PMID- 12183906
TI  - [Drug policy in Slovakia and its reflection in prescriptions. 2. Prescriptions of
      individually prepared drugs based on the medical specialty].
AB  - The paper aims to analyze the frequency of medical prescriptions for the group of
      extemporaneously prepared drugs in relation to the specialization of physicians.
      The evaluation is based on the database of prescriptions dispensed by four
      pharmacies within 14.5 months in the years 1999-2000. The total number of
      prescriptions was 133,857, out of which 5615 (4.2%) were extemporaneous
      preparations. The share of specialists in the prescription of extemporaneous
      drugs was 7%, that of general practitioners, 1.4%. Out of the specialists, the
      largest share in the prescription of extemporaneously prepared drugs belonged to
      dermatologists, otorhinolaryngologists, and pediatricians. The economic aspect of
      prescription of the group of extemporaneous drugs was also evaluated. The average
      value of a medical prescription for an extemporaneously prepared drug was 68.40
      SK, which represents 17.8% of the average value of a medical prescription for a
      mass-produced drug.

PMID- 12183905
TI  - [Effect of a fungal elicitor on levels of sanguinarine and polyphenoloxidase
      activity in a suspension culture of Papaver somniferum L].
AB  - The opium poppy (Papaver somniferum L.) is still a source for isolation of
      codeine and morphine. Cell cultures from this plant lose their ability to produce
      morphinans. Their major alkaloid is sanguinarine. The elicitation of the opium
      poppy cell cultures by fungal preparation lead to a nine-fold increase in the
      content of sanguinarine. The specific activity of polyphenoloxidase (PPO) was
      three-times higher in the elicited compared to the nonelicited cells. Two
      isoforms of PPO (Mr 63 kDa, 41 kDa) were identified in opium poppy cell cultures
      by PAGE. The number of PPO isoforms was not affected by elicitation. Phenyl
      Sepharose CL-4B was used for affinity purification of PPO. In a single
      purification step the specific activity of PPO was enriched 14-fold.

PMID- 12183907
TI  - [Treatment of allergic rhinitis in clinical practice and its pharmacoeconomic
      aspects].
AB  - The present paper aims to analyze therapeutic trends in allergic rhinitis and
      their relationships to selected pharmacoeconomic parameters. Health and Disease
      out-patient records from three out-patient allergologic-immunologic surgeries in
      the towns of Trencin, Nove Zamky, and Bratislava were surveyed. The analysis is
      based on the recorded prescription of drugs prescribed to the patients in the
      period of his or her "most recent season" in the years 1999-2000. Altogether 279
      records (164 females, 115 males) were evaluated. The highest percentage of
      pollinotics was dispensed in Bratislava (73%) followed by Nove Zamky (55%) and
      Trencin (31%). In all three out-patient surgeries, the dominant therapy was a
      combination of specific immunotherapy (SIT) and antihistanime treatment (AH, 70
      75%). Average costs for one day of treatment of allergic rhinitis in the out
      patient surgeries under study did not significantly differ (22.20-24.50 Sk, the
      average value of the daily defined dose being 23.20 Sk). Due to confused kept
      records, the economic analysis did not take into account the financial costs
      connected with SIT. The present analysis shows a positive state in the field of
      diagnostics, connected with improved identification of the inducing allergen and
      application of causal therapy based on SIT (72%). Approximately one third of
      patients (27%) received only solo medicamentous therapy without application of
      SIT, and the SIT therapy alone was received by less than 2% of patients (1.4%).

PMID- 12183908
TI  - [Conformational study of drugs which affect I1-imidazoline receptors].
AB  - Conformational analysis of five I1-receptor agonists in the neutral form
      (clonidine, moxonidine, rilmenidine, phentolamine, and phencyclidine) and one
      antagonist of I1-receptors (idazoxane) was carried out by means of the MM2
      method. Structures of stable conformations of individual compounds were fully
      optimised. Degree of similarity of stable conformations was visualized. The
      proton affinities and lipophilicities of title compounds were also computed. It
      is obvious that all studied drugs except phencyclidine are able to occupy the
      same space. An important role for affinity of studied drugs towards I1-receptors
      can be played by their different hydrophobicity (logP = 1 az 2).

PMID- 12183909
TI  - [Effect of fillers on the strength of silicone systems].
AB  - The present paper examines the strength behaviour of addition silicone systems
      composed of Lukopren A 6200 and three inorganic fillers (Skron SF 600, Cab-O-Sil
      LM 150, sodium chloride) in different concentrations and particle sizes. The
      tensile strength sigma (MPa) and the relative lengthening of samples on rupture
      epsilon (%) were measured. With increasing concentration of the filler in the
      system relative lengthening of matrices is decreased. This trend corresponds with
      the theoretical hypotheses and it is understandable also with regard to the fact
      that the filler, in comparison with silicone rubber, possesses very low
      ductility. An addition of Sikron increases tensile strength of samples.
      Dependence of tensile strength on the amount of Sikron in the system is linear.
      This behaviour is typical of fibrous composites and the composites with high
      adhesion between the filler and matrix. Concentrations of Cab-O-Sil up to 5% did
      not exert an effect on tensile strength. An important increase in strength was
      shown only by the systems containing 10% of Cab-O-Sil. Experimental dependence of
      tensile strength on the amount of Cab-O-Sil in the system can be described by the
      equation for composites with Hookean behaviour till destruction. The effect of
      sodium chloride on tensile strength is more complicated. In the systems with NaCl
      particles of 20 microns, strength is not practically changed up to a content of
      40% of NaCl in the system. In larger size fractions, tensile strength is
      decreased, and with a change in particle size, shape is probably changed as well.

PMID- 12183910
TI  - [Anti-inflammatory activity of (o-cresotinate) copper and zinc aquacomplexes].
AB  - Using rat paw dextran-induced and carrageenan-induced edemas, the antiedematous
      activities of monohydrate of the diaquatetrakis(o-cresotato)dicopper(II) complex
      (CuoC) and the diaquabis(o-cresotato)zinc(II) complex (ZnoC) were assayed
      plethysmometrically. Dihydrate of the diaquabis(salicylato)copper(II) complex
      (CuS) and the diaquabis(salicylato)zinc(II) complex (ZnS) were used as the
      standards of comparison. All compounds were administered i.p. in a single dose of
      50 mumol/kg body weight (calculated for the RCOO-fragment) 30 min before
      injecting the irritants. The antidextran/anticarrageenan activities of the
      species (expressed as a mean edema reduction) were found: CuoC 36/54%--ZnoC
      59/65%--CuS 71/52%--ZnS 63/10%. The relationships between the coordination
      chemical properties and the biological effects of the corresponding complexes are
      discussed.

PMID- 12183911
TI  - [Whether or not to get children when a hereditary disease is worrying you?].

PMID- 12183912
TI  - [Catheter ablation of atrial fibrillation].

PMID- 12183913
TI  - [A patient with multiple sclerosis can be vaccinated].

PMID- 12183914
TI  - [Year 2001 Anders Jahre Award to Leena Ala-Kokko].

PMID- 12183915
TI  - [Acute inflammatory reaction caused by bacterial structures].

PMID- 12183916
TI  - [Imaging of acute brain infarction].

PMID- 12183917
TI  - [Long term prognosis and quality of life after coronary by-pass surgery].

PMID- 12183918
TI  - [Malign pheochromocytoma behaving as a benign tumor].

PMID- 12183919
TI  - [Milk is coming out from the baby's thoracic cavity...].

PMID- 12183920
TI  - [Adapters].

PMID- 12183922
TI  - [Abortion].

PMID- 12183921
TI  - [The mystery of missing flatulence].

PMID- 12183923
TI  - [Illness as an contraindication for pregnancy].

PMID- 12183924
TI  - [Anxiety disorders in adolescents and young adults].

PMID- 12183925
TI  - [Why does tube feeding not work?].

PMID- 12183926
TI  - [Is screening of colorectal cancer by endoscopy economically profitable?].

PMID- 12183927
TI  - [Corticobasal degeneration].

PMID- 12183928
TI  - [Snowstorm in the lungs].

PMID- 12183929
TI  - [Chediak-Higashi syndrome: a rare disease in Northern Finland].

PMID- 12183930
TI  - [Macroamylasemia--an elevated blood amylase level without an illness].

PMID- 12183931
TI  - [Treatment of menorrhagia].

PMID- 12183932
TI  - [Horner and headache].

PMID- 12183933
TI  - [Light to the darkness of medicine!].

PMID- 12183934
TI  - [The area between brain and mind--a neurologist is needed in a psychiatric
      hospital].

PMID- 12183935
TI  - The Australian experience of day programs for patients with eating disorders.
AB  - OBJECTIVE: To describe the authors' experience in establishing and implementing
      day programs for the treatment of eating disorders in Australia. METHOD: This is
      a descriptive article based on the author's experience. Five-day programs are
      described in terms of their structure, theoretical orientation, and intended
      outcome. RESULTS & DISCUSSION: The authors conclude that day programs need to be
      matched to the heterogeneous needs of the patients according to their stage of
      change. The further the patient is towards an action stage of change the less
      supervision of their eating- and skills-based therapy is required. Accordingly,
      treatment can be more focused on understanding the factors that maintain the
      eating disorder on a more extensive day program. Patients with longstanding
      eating disorders that have not responded to traditional treatments may benefit
      from a readiness and motivational therapy approach in a day program.

PMID- 12183936
TI  - Social anxiety as a barrier to treatment for eating disorders.
AB  - BACKGROUND: The goal of this pilot investigation is to determine the relationship
      between social anxiety and treatment-seeking behavior for eating disorders in an
      outpatient psychiatric clinic. METHOD: Twenty-eight patients seeking treatment
      for anorexia or bulimia at an outpatient eating disorders clinic completed a
      battery of self-report measures on eating pathology, attachment style and
      functioning, and social anxiety at initial intake appointment. Levels of eating
      pathology and social anxiety at consult were compared with service utilization
      records on entry into treatment. RESULTS: Individuals who did not engage in
      treatment had significantly higher levels of social anxiety (F = 8.29, df = 1, p
      < .05) compared with those who did engage in treatment. There were no differences
      in demographic characteristics, diagnoses, or level of eating pathology at
      intake. CONCLUSIONS: Social anxiety may act as a barrier to effective help
      seeking and utilization of mental health treatment among individuals with eating
      disorders. Replication of these findings in a larger sample and more in-depth
      study of the mechanism of the observed association between use of services and
      social anxiety may be useful in planning more effective outreach in the community
      to underserved populations in need of treatment for eating disorders.

PMID- 12183937
TI  - The relationship between compulsive buying and eating disorders.
AB  - OBJECTIVE: Compulsive buying has received increased research attention in the
      last decade. The disorder has high rates of comorbidity for other disorders,
      including eating disorders. This study explored the possible relationship between
      compulsive buying and eating disorders. METHOD: Twenty women who scored in the
      pathological range on a measure of compulsive buying and 20 controls were
      recruited via the media. Various measures of psychopathology and eating disorder
      symptoms were administered to both groups. RESULT: Compulsive buyers were
      significantly more likely to have a higher lifetime history of substance abuse or
      dependence. No differences existed between normal controls and compulsive buyers
      in prevalence of current or lifetime eating disorders, nor were there differences
      in scores of eating-related psychopathology. DISCUSSION: This work failed to
      demonstrate an increased risk for eating disorder in compulsive buyers, although
      a higher rate of substance dependence or abuse and higher scores on pathological
      personality dimension scales were seen.

PMID- 12183938
TI  - Pattern of birth in anorexia nervosa. I: Early-onset cases in the United Kingdom.
AB  - OBJECTIVES: Previous studies suggest that adults with anorexia nervosa are more
      likely to be born in spring and early summer. This study examines whether this
      pattern of birth is true of early-onset anorexia nervosa, and whether there is a
      relationship between environmental temperature at assumed time of conception and
      a later diagnosis of anorexia nervosa. METHOD: The population were children and
      adolescents with diagnoses of anorexia nervosa (N = 259) or "other eating
      disorders" (N = 149). Distribution of births across the year was compared between
      groups and relative to standard population norms. Temperature at assumed time of
      conception was taken from meteorological records. RESULTS: There was a
      significant preponderance of births among those with anorexia nervosa between
      April and June, compared with the other months of the year and with the "other
      eating disorders" group. Anorexia nervosa was also associated with higher
      environmental temperature at assumed time of conception. CONCLUSIONS: Among early
      onset cases in the United Kingdom, patients with anorexia nervosa are more likely
      to be born between April and June, and to be conceived during warmer months. A
      tentative "temperature at conception" hypothesis is advanced to explain these
      findings and to generate further research.

PMID- 12183939
TI  - Chewing and spitting out food among eating-disordered patients.
AB  - OBJECTIVE: The symptom of chewing and spitting out food (CHSP) is fairly common
      among patients with eating disorders. The purpose of this study is to examine the
      associations of the symptom in patients with eating disorders. METHOD: Patients
      who reported CHSP were compared with those who did not. The relationship between
      CHSP and other symptoms was assessed by logistic regression analysis. RESULTS:
      CHSP was found in 22% of patients. Patients with anorexia nervosa and eating
      disorder not otherwise specified who reported CHSP showed more severe eating
      related pathology. This was not so for bulimia nervosa patients with CHSP who
      differed only in reporting greater distortion of body image. Binging was not
      related to CHSP in any of the diagnostic groups. DISCUSSION: CHSP is a common
      symptom in all groups of patients with eating disorders. The symptom may serve
      different functions for different patients, depending on diagnosis.

PMID- 12183940
TI  - Coping style and disturbed eating attitudes in adolescent girls.
AB  - OBJECTIVE: The main goal of this work was to explore the relationship between
      coping styles and predisposition to eating disorders in a sample of adolescent
      girls. METHOD: The sample comprised 186 females (mean age 15.91 years) and the
      questionnaires used were the Eating Disorders Inventory-2 (EDI-2) and the
      Adolescent Coping Scale (ACS). RESULTS: The regression analyses indicated that
      the coping strategy most closely linked to the predisposition to develop an
      eating disorder was intropunitive avoidance, which explained the following
      percentage of variance: 29% of the total EDI-2 score, 23% of the personal factor,
      28% of the social factor, and 4% of the bodily factor. On the other hand, the
      scale of intropunitive avoidance dimension with the most explanatory power was
      the tension reduction, which reflects emotional reactions to problems such as
      crying, shouting, or taking drugs. DISCUSSION: A cultural hypothesis is presented
      in an attempt to account for the low percentage of variance of bodily factor
      explained by intropunitive avoidance and emphasis is placed on the need for
      prevention programs for adolescents, particularly those at risk.

PMID- 12183941
TI  - A case of anorexia nervosa with severe hyperlipoproteinemia.
AB  - OBJECTIVE: The complication of severe hyperlipoproteinemia with anorexia nervosa
      is very rare. We investigated the mechanisms of severe hyperlipoproteinemia in a
      patient with anorexia nervosa. METHODS: The measurement of plasma levels of
      lipids, apolipoproteins (Apo), lipoprotein subfractions, free T3, and estrogen,
      apo (lipoprotein) E phenotyping, and the assay of lymphocyte low-density
      lipoprotein (LDL)-receptor activity were accomplished in a 40-year-old female
      patient with anorexia nervosa. RESULTS: Her body mass index was 10.3 kg/m2. Her
      plasma levels of total cholesterol (C), triglyceride (TG), apoB, apoE, very-low
      density lipoprotein (VLDL)-C, and intermediate-density lipoprotein (IDL)-C were
      757 mg/dl, 526 mg/dl, 288 mg/dl, 13.6 mg/dl, 133 mg/dl, and 99 mg/dl,
      respectively. VLDL was cholesterol rich (C/TG ratio = 0.68; normal value = 0.2).
      The plasma LDL was high and skewed to less dense fractions. Her apoE phenotype
      was E 3/2. Her lymphocyte LDL-receptor activity was 79% of normal subjects. The
      plasma level of estradiol was low and that of free T3 was subnormal. DISCUSSION:
      We concluded that the plasma lipoprotein abnormality of this anorexia nervosa
      patient was induced by the impaired removal of TG-rich lipoprotein remnants and
      less dense LDL due to apoE phenotype E 3/2, subnormal LDL-receptor activity,
      subnormal plasma level of free T3, and diminished secretion of estrogen.

PMID- 12183942
TI  - Pattern of birth in anorexia nervosa. II: A comparison of early-onset cases in
      the southern and northern hemispheres.
AB  - OBJECTIVE: In the northern hemisphere, people with anorexia nervosa are more
      likely to be born in the spring and early summer, particularly when environmental
      temperature at assumed time of conception is warmer. This study investigates
      whether there is a comparable effect in the southern hemisphere (Australia),
      where seasonal and temperature patterns are reversed. METHOD: Date of birth and
      temperature at assumed time of conception were collected for 199 Australian and
      259 UK patients with early-onset anorexia nervosa. Analyses determined patterns
      of birth and links to temperature at conception. RESULTS: There was little change
      across the year in the birth patterns of young people with anorexia nervosa in
      the southern hemisphere. However, there was a significant link between
      temperature at assumed time of conception and diagnostic subtype. Compared with
      anorexics of the binge/purge subtype, restrictive anorexics from the southern
      hemisphere were less likely to be conceived in relatively cool weather.
      CONCLUSIONS: The findings support a temperature at conception hypothesis
      (modified for local temperature ranges), rather than suggesting a simple seasonal
      pattern of birth.

PMID- 12183943
TI  - The Anorexia Nervosa Stages of Change Questionnaire (ANSOCQ): information
      regarding its psychometric properties.
AB  - OBJECTIVE: The Anorexia Nervosa Stages of Change Questionnaire (ANSOCQ) was
      developed to assess patients' readiness to recover from anorexia nervosa. In this
      article we present additional findings supporting the psychometric properties of
      the ANSOCQ. METHOD: Forty-four inpatients with anorexia nervosa participated in
      the study. At the time of admission, patients were requested to complete the
      ANSOCQ as well as several other self-report questionnaires assessing constructs
      related to readiness to change. RESULTS: The ANSOCQ demonstrated good construct
      related validity in that significant correlations emerged between the ANSOCQ and
      instruments assessing the theoretically related constructs of decisional balance
      and self-efficacy. DISCUSSION: Having developed a reliable and valid self-report
      questionnaire for the assessment of readiness to change in anorexia nervosa, the
      ANSOCQ provides a means of addressing motivational hypotheses which have been
      advanced in the context of eating disorders.

PMID- 12183944
TI  - Variables associated with disturbed eating habits and overvalued ideas about the
      personal implications of body shape and weight in a female adolescent population.
AB  - OBJECTIVES: Few studies exist that examine risk factors for the overvalued ideas
      about the personal implications of body shape and weight that are viewed as the
      central cognitive substrate of eating disorders. METHOD: In a female adolescent
      population (mean age = 14 years, SD = 0.7), we examine variables previously
      identified in the literature as risk factors for eating disorders, namely, self
      esteem, comments from others about eating/weight/shape, perfectionism, childhood
      and parental weight/shape, and parental conflict. RESULTS: These variables were
      all correlated significantly with current (past 4 weeks) levels of overvalued
      ideas and disturbed eating patterns in the predicted directions. Self-esteem was
      found to mediate partially the relationship between the overvalued ideas and
      comments about weight and perfectionism. Self-esteem fully mediated the
      relationship between the overvalued ideas and parental conflict. A family index
      of body size had an independent influence on the overvalued ideas, that is, the
      bigger the size, the greater the overvalued ideas. Finally, the overvalued ideas
      fully accounted for the relationship between self-esteem and disturbed eating
      patterns. DISCUSSION: The cognitive model of bulimia nervosa is supported by the
      results of this study. Self-esteem represents an important gateway to the
      overvalued ideas that contribute substantially to disturbed eating patterns.

PMID- 12183945
TI  - Development of body image, eating disturbance, and general psychological
      functioning in adolescent females: a replication using covariance structure
      modeling in an Australian sample.
AB  - OBJECTIVE: The current study is a follow up to a covariance structure modeling
      (CSM) investigation of predictors of body image, eating dysfunction, and general
      psychological functioning in U.S. adolescent females. METHOD: Four hundred and
      seventy Australian girls (13-17 years old) completed measures of teasing history,
      body dissatisfaction, global psychological functioning, dietary restraint, and
      bulimic behaviors. They were also measured in order to compute body mass index
      (BMI). CSM techniques were used to analyze the relationships between these latent
      variables. Two a priori models were tested, one was selected, and post-hoc model
      fitting was undertaken. RESULTS: The final model indicated that BMI directly
      influenced teasing, which directly influenced body dissatisfaction. Body
      dissatisfaction influenced both global psychological functioning and restriction,
      whereas restriction had a direct influence on bulimia. Global psychological
      functioning also had a direct influence on bulimia. DISCUSSION: The results
      support previous research indicating that teasing and body dissatisfaction are
      risk factors for the development of eating disturbances.

PMID- 12183946
TI  - Preoccupation with weight and disordered eating behaviors of entering students at
      a university in Lebanon.
AB  - OBJECTIVES: This research explores the prevalence of preoccupation with weight
      indicators and disordered eating behaviors among entering university students,
      and identifies factors associated with these indicators and behaviors. METHOD:
      Data was collected by means of a self-administered questionnaire. Comparisons
      were made by gender, mother's education, and body mass index (BMI). RESULTS: The
      final sample included 954 students. The indicators held most "often" included a
      desire to be thinner, and an awareness of caloric content. The behaviors engaged
      in "most" often included strenuous exercising, and avoiding particular foods.
      Both indicators and behaviors varied by gender and body mass index. DISCUSSION:
      The prevalence of indicators and behaviors is high. Body mass index is a critical
      variable to consider in the development of interventions. Further research should
      explore the context surrounding these indicators and behaviors.

PMID- 12183947
TI  - Links between body mass index, total body fat, cholesterol, high-density
      lipoprotein, and insulin sensitivity in patients with obesity related to
      depression, anger, and anxiety.
AB  - OBJECTIVE: Define links between psychosocial parameters and metabolic variables
      in obese females before and after a low-calorie diet. METHOD: Nine female obese
      patients (age 36.1 +/- 7.1 years, body mass index [BMI] > 30 kg/m2) were
      investigated before and after a 6-week low-calorie diet accompanied by behavior
      therapy. Blood lipids, insulin sensitivity (Bergman protocol), fat distribution
      (by dual-energy X-ray absorptiometry [DEXA]), as well as psychological parameters
      such as depression, anger, anxiety, symptom load, and well-being, were assessed
      before and after the dieting period. RESULTS: The females lost 9.6 +/- 2.8 kg (p
      < .0001) of body weight, their BMI was reduced by 3.5 +/- 0.3 kg/m2 (p < .0001),
      and insulin sensitivity increased from 3.0 +/- 1.8 to 4.3 +/- 1.5 mg/kg (p =
      .05). Their abdominal fat content decreased from 22.3 +/- 5.5 to 18.9 +/- 4.5 kg
      (p < .0001). In parallel, psychological parameters such as irritability (p < .05)
      and cognitive control (p < .0001) increased, whereas feelings of hunger (p <
      .05), externality (p < .05), interpersonal sensitivity (p < .01), paranoid
      ideation (p < .05), psychoticism (p < .01), and global severity index (p < .01)
      decreased. Prospectively, differences in body fat (percent) were correlated to
      nervousness (p < .05). Waist-to-hip ratio (WHR) differences were significantly
      correlated to sociability (p < .05) and inversely to emotional instability (p <
      .05), whereas emotional instability was inversely correlated to differences in
      insulin sensitivity (p < .01). DISCUSSION: Weight reduction may lead to better
      somatic risk factor control. Women with more nervousness and better sociability
      at the beginning of a diet period may lose more weight than others.

PMID- 12183949
TI  - The effect of fasting on attentional biases for food and body shape/weight words
      in high and low Eating Disorder Inventory scorers.
AB  - OBJECTIVE: To assess attentional biases associated with food and body
      shape/weight words in fasted and nonfasted high and low Eating Disorder Inventory
      2 (EDI-2) scorers. METHOD: Subjects were 56 female first-year undergraduate
      psychology students, aged 17-24 years, participating for course credit. High and
      low scorers on the Drive for Thinness and Body Dissatisfaction subscales of the
      EDI-2 completed alternative modified dot probe tasks containing food words, body
      shape/weight words, and control words, under fasted and nonfasted conditions.
      RESULTS: Fasting increased attentional bias toward high-calorie food words across
      all subjects. High EDI-2 scorers also showed an attentional bias toward low
      calorie words, but only when nonfasted. DISCUSSION: Food-related attentional
      biases, commonly observed in eating disorder patients, may reflect a pervasive
      concern with food-related stimuli as opposed to being simply a product of chronic
      hunger. That is, with increasing hunger, high EDI-2 scorers shift their focus
      away from low-calorie foods to high-calorie foods. This result suggests an
      attentional bias basis for the cycle of high-calorie binging when hungry and low
      calorie food selections when less hungry.

PMID- 12183950
TI  - Screening Chinese patients with eating disorders using the Eating Attitudes Test
      in Hong Kong.
AB  - OBJECTIVE: To evaluate the Chinese Eating Attitudes Test (EAT-26) in screening
      patients with anorexia nervosa (AN) and bulimia nervosa (BN) in Hong Kong.
      METHOD: A consecutive series of Chinese patients with BN (N = 67) and typical
      (fat phobic; N = 65) and atypical (nonfat phobic; N = 44) AN underwent clinical
      assessment and completed the EAT-26. Results were compared with those of Chinese
      female undergraduates (N = 646). RESULTS: The mean EAT scores for bulimic and
      typical AN patients were significantly higher than those of undergraduates, but
      the scores of atypical AN patients were anomalously low. The dieting and bulimia
      factor, scores and body mass indices entered the classification tree. When
      compared with using the conventional EAT-26 cutoff, the misclassification rate
      for typical AN, atypical AN, and BN changed from 41.4% to 52.3%, 88.6% to 43.2%,
      and 23.9% to 29.9%, respectively. DISCUSSION: Using the EAT-26 in the
      conventional manner would lead to an underestimate of atypical AN in community
      surveys. Complementary use of a classification tree improved the prediction of
      atypical AN, but the EAT-26 remains a suboptimal screening instrument for the
      community epidemiological study of AN.

PMID- 12183948
TI  - Medical and psychiatric morbidity in obese women with and without binge eating.
AB  - OBJECTIVE: To determine the prevalence of obesity and binge eating in a
      population-based sample of female twins and to examine whether the presence of
      binge eating was associated with a greater risk for medical and psychiatric
      disorders in obese women. METHOD: A population-based study of twins who were born
      between 1934 and 1971 and both members responded to a mailed questionnaire
      (individual response rate was conservatively estimated to be 64%). Data for the
      present study are from the first and third interview waves. In Wave 1 (1987
      1989), we assessed 92% of the eligible individuals (N = 2,163), 90% face-to-face
      and the remainder by telephone. We assessed lifetime history of psychiatric
      disorders, major medical disorders, health limitations, health satisfaction, and
      an array of personality and attitudinal measures. RESULTS: Obese women with binge
      eating reported greater health dissatisfaction and higher rates of major medical
      disorders than obese women without binge eating. Binge eating was also associated
      with higher lifetime prevalence of major depression, panic disorder, phobias, and
      alcohol dependence. Obese women with binge eating scored higher on neuroticism
      and symptom scales measuring depression, anxiety/phobia, and neurovegetative
      symptoms (i.e., insomnia, agitation, retardation, and obsessive-compulsive
      traits). DISCUSSION: The presence of binge eating in obese women is a marker for
      greater medical and psychiatric morbidity.

PMID- 12183951
TI  - Impulsive behaviors in bulimic patients: relation to general psychopathology.
AB  - OBJECTIVE: At a general level, impulsivity is related to both bulimic and general
      psychopathology. However, it is a complex construct, and the specific role of
      different forms of impulsivity in psychopathology remains to be determined. The
      present study of bulimic outpatients examined the association of internally and
      externally directed impulsive behaviors with general and bulimic psychopathology.
      METHODS: Thirty female bulimic outpatients completed standardized measures of
      bulimic attitudes/behaviors, general psychopathology and impulsive behaviors.
      RESULTS: While general psychopathology was associated with internally directed
      impulsive behaviors (e.g., self-harm), bulimic pathology was more specifically
      linked with externally directed impulsivity (e.g., theft; reckless driving).
      DISCUSSION: The results indicate that the bulimia-impulsivity link in eating
      disordered patients is not simply a by-product of the broader association of
      impulsivity with psychopathology. Therefore, bulimic pathology does not seem to
      be just a manifestation of general psychological disturbance. Further research is
      suggested to test these results and potential clinical implications are outlined.

PMID- 12183952
TI  - [Contraceptive pills keep our minds occupied].

PMID- 12183953
TI  - [Is the eradication of polio successful in Finland and elsewhere?].

PMID- 12183954
TI  - [Challenges of hearing rehabilitation].

PMID- 12183955
TI  - [Nobel prize 2001 given for explanation of the mysteries of cell-division cycle].

PMID- 12183956
TI  - [Raimo Suhonen-- the recipient of Konrad Reijo Waara Award].

PMID- 12183957
TI  - [The Young Scientist Award of Duodecim Society to Professor Kristiina Vuori].

PMID- 12183958
TI  - [Preimplantation diagnostics].

PMID- 12183959
TI  - [From research of cellular stress to various clinical break through
      innovations?].

PMID- 12183960
TI  - [The clinical significance of umbilical knot in obstetrics].

PMID- 12183961
TI  - [Protein C deficiency and use of anabolic steroids behind the myocardial
      infarction in a young man].

PMID- 12183962
TI  - [Inflammatory pseudotumor of the trachea in a young woman].

PMID- 12183963
TI  - [Visual hallucinations in a small boy].

PMID- 12183964
TI  - [ECG changes caused by pneumothorax].

PMID- 12183965
TI  - [Ovarian cancer].

PMID- 12183966
TI  - [Diabetes mellitus in the elderly].
AB  - The prevalence of diabetes increase in the elderly. Ageing is one of the most
      important factors contributing to development of glucose intolerance (insuline
      resistance). NHANES II data showed that in the poppulation over 65 years 18.7%
      has got overt diabetes and  22.8% glucose intolerance. Similar data were obtained
      among ageing inhabitants of the city of Bialystok (downtown). The criteria of
      diagnosis of  diabetes in the elderly are the same like in the younger
      population. However, in the elderly the clinical symptoms are not characteristic
      and scanty (limited). The period without symptoms is long. Very often, the
      diabetes is diagnosed for the first time in patient with the heart infarct, brain
      stroke, diabetic foot or even hyperosmolar coma. There may occur two critical
      situations in the elderly diabetic persons, namely non-ketotic hyperosmolar coma
      and hypoglycameia. The non-ketotic hyperosmolar coma is a result of a
      considerable elevation in the blood concentration of glucose, sodium and urea.
      This, in turn, is a consequence of osmotic diuresis which  is non balanced by
      elevation in the volume of water intake. Factors facilitating development of  the
      coma include: nontreated diabetes, infirmity, inadequate care, diuretics, stroke,
      hyperthermia. Hypoglycaemia in the   elderly is a very serious problem. It can
      cause arrhythmia, a rise in the blood pressure, unconsciousness, falls and
      injuries. The most often reason of hypoglycaemia in the elderly are: long-acting
      derivatives of sulphonylurea, treatment with insulin and irregular meals. The
      major aims of treatment of diabetes in the elderly are: reduction of 
      hyperglycaemia, reduction in the development of complications and minimizing of
      the risk of hypoglycaemia. An elderly patient with diabetes should have each year
      a check-up which would include examination of the eyes, kidneys, feet. The
      elderly patient with diabetes is often crippled, indolent and lives often alone.
      Therefore, such a patient should be taken care of by a team of people. The most
      important role in the team should be played by a family physician and a social
      nurse.

PMID- 12183967
TI  - [Advanced age toxicology].

PMID- 12183968
TI  - [Regional diversity in the situation of the elderly in rural areas].
AB  - The situation of the elderly in Poland differs, sometimes quite significantly,
      among regions and smaller areas of the country. It concerns particularly rural
      areas. The study, initiated by the Polish Society of Gerontology in the years
      1999-2001 in six chosen rural areas, allowed the evaluation of these differences.
      The percentage of people over 65 in rural areas in Poland is, on the average,
      13.2%, while in the studied rural areas it reaches from 9.3% in Chmielno (region
      Kaszuby) to 27.4% in Narew (region Podlasie). The percentage of the elderly with
      incomplete primary education amounted from 11% in Chmielno (region Kaszuby) to
      80% in Punsk (region Podlasie). In Polish villages 59.9% of the people over 65
      evaluate their health as bad or very bad; in the studied areas this evaluation
      was given by 36% of the respondents in Krapkowice (region Slask Opolski) to 58%
      in Lewin in the same region and in three studied areas in the those unsatisfied
      with their material situation ranged from 24% in Dziadkowice and Narew (region
      Podlasie) to 44% in Chmielno (region Kaszuby). In Poland 11.4% of the elderly
      express their lack of life satisfaction and life achievement. In the studied
      areas the percentage of the unsatisfied ranged from a few percent (Chmielno) to
      over 20% (Punsk). Such diversity can be explained through both emotional and
      economic, as well as psychological or ethnic factors, and social traditions. The
      presented study indicates that planning of resources to satisfy the health,
      economic and social needs of the elderly cannot be based exclusively on general
      statistical indices for whole Poland, but should also take into consideration
      local demographic and economic conditions as well as specific ethnic,
      environmental and tradition based factors.

PMID- 12183969
TI  - [Health care services for the elderly living in the rural area of Poland].
AB  - The aim of the paper was the indepth comparison of the health services use by the
      elderly living in rural and urban area of Poland. The representative survey of
      the 65-year old and older people was carried out in the year 2000, as a
      comparative study to the Piotrowski's survey from 1967. The sample (total N =
      1821; consisted of 743 people living in rural and 1078 in urban area), was
      corresponding to the demographic structure of the general older population in
      Poland. RESULTS: As far as concerning socio-demographic features there were found
      slightly higher percentage of 'old old' people in rural community, their much
      worse living conditions and material situation in comparison to counterparts in
      urban community. The elderly living in the countryside have shown the worse
      subjective and objective health and functional indices. The positive selfrated
      health was found only in 12% of respondents living in rural and in 22% living in
      urban area. 71% people living in villages declared three or more complaints
      simultaneously while in the cities much less (57%). Moreover, the impairment of
      vision, hearing, chewing were found significantly more frequently among rural
      inhabitants, as well as almost twice higher percentages of dependence on P-ADL.
      The use of health services by the elderly during the last 12 months, in term of
      doctor's outpatient consultations, dentist visits rehabilitation, except of nurse
      visits, was significantly lower in countryside than in the cities. Use of an
      emergency (17%) and hospital stays (22%) was the same in the both sites.
      CONCLUSIONS: (1) Health status and functional ability of the older people living
      in rural area are dramatically worse than in cities. (2) Health care system for
      elderly people in Poland does not fulfill the geriatric standards in term of the
      commonness, availability and complexity. (3) The chance to improve health care on
      the elderly is an enhancement of knowledge and competence of practitioners in
      gerontology. The development of the geriatric base in the Medical Universities is
      a crucial for that.

PMID- 12183971
TI  - [The elderly in Lublin Province and in Poland in the demographic prognoses].
AB  - The aim of the paper is presentation of the issue of increase in number of the
      elderly in Lublin province and in Poland in the next 30 years. There were
      analysed demographic prognoses concerning age structure of the population of
      Lublin province and Poland until the year 2030, elaborated by the Main
      Statistical Office (GUS). There were taken under account age groups over 65 years
      of age, men and women. It was concluded that the percentage of the elderly in the
      studied populations will increase considerably, which is especially evident in
      females--in 2030 almost every fourth women in Poland will be aged 65 or more. The
      increase in number of the elderly citizens will change structure of employment
      and will force adequate modifications in social and health policy in Poland in
      order to meet the requirements of this age group and allow its due status in the
      society.

PMID- 12183970
TI  - [The spreading of big geriatric centers in the community dwelling elderly: the
      challenge for the primary health care].
AB  - As the giants of geriatrics are considered: immobility, instability,
      incontinence, intellectual impairment, depression, visual and auditory
      impairment. They have multiple causation, chronic course, no simple cure and make
      the elderly person dependent on others for care. The paper presents the results
      of the study on the prevalence of the giants of geriatrics in community dwelling
      elderly people 75 yers old +. The study design: cross-sectional questionnaire
      study, survey. Population studied lived in two chosen areas (the urban and the
      rural one) with the high percentages of the demographic senility. The
      interviewers were doctors and nurses serving the studied areas. 463 randomly
      selected elderly people (233 from the rural and 230 from the urban area) took
      part in the study. The serious locomotive disability (III/IV group according to
      J. Piotrowski) was observed in 17.1% of the probands (20.4% in the urban and
      13.7% in the rural area; the worse locomotive ability was observed in women and
      in the older age groups.). Falls were reported by 45.1% of the group (more
      frequently by women and in the rural area--58.3% vs. 31.9% in the city). Visual
      impairment reported 21.1% of probands in the urban area and above 50% in rural
      one and auditory impairment respectively 30.8% and 53.9% of them (in both cases
      positive correlation with the age was noticed). Incontinence of urine was found
      in 31.7% of cases in the city and in 46% of them in the rural area (more
      frequently in women) and incontinence of faeces in 6% (without urban/rural
      differences). The pathologic result of the Geriatric Depression Scale was
      observed in 49.2% of the elderly (more frequently in women) and of the Cognitive
      Impairment Test by Katzman in 20.5% (more frequently in women and in the older
      age groups). Only 18.4% of the studied group of the elderly maintained the
      community nurse visited their home during the last 12 months (27.8% in the city
      and 9% in the rural area) and more frequently--34.3%--general practitioner
      (respectively 48.7% and 20.2%). The marginal percentage of the elderly (and only
      in the city) received any kind of physical rehabilitation or contacted the social
      worker. In the presence of high rate of disability in the elderly population the
      most important need is the development of community care for the elderly with the
      great emphasis on the role of community/home nurses and rehabilitation
      institutions for the elderly on the primary care level.

PMID- 12183972
TI  - [Changes in average life span of monks and nuns in Poland in the years 1950
      2000].
AB  - The aim of the research was to find out if healthy lifestyle influences the
      longevity. The group of 906 monks and 866 nuns who worked and died in Poland in
      the years 1950-2000 was regarded as people who conducted a healthy lifestyle. The
      population of adult Poles was chosen as a control group. As a result of the
      research it is reported that: 1) since 1950 till middle 1960's people in
      monasteries lived shorter than adult Poles [in the first ten years of the
      research the average life span of monks was 2.4 years shorter (t162 = 1.99, p =
      0.047) and nuns lived 9 years shorter (t56 = 4.2, p < 0.001)], since the middle
      of 1970's till the end of 1980's the group in question lived as long as the
      general population, finally, for the last ten years of the investigated period of
      time people in monasteries lived longer [monks 2.5 (t219 = 2.5, p < 0.05), nuns
      2.9 years longer (t209 = 4.6, p < 0.001)]; 2) since 1950's till 2000 the average
      life span in the investigated group of both sexes was increasing at the rate of
      0.175 (t98 = 3.9, p < 0.001) years per calendar year greater than this value in
      the general population and there is no reason to assume that there have been
      differences between sexes; 3) as far as men are concerned, joining a monastery in
      the case of man enter into the monastery a year earlier prolongs life for about
      0.1 year (F1,842 = 3.8, P one side test = 0.026). In case of women this relation
      was not significant (F1,804 < 0.1). The shorter life of people in monasteries
      after the second world war might be interpreted as a result of their socio
      political situation at that time. In the course of time their standard of living
      and the access to medical treatment has been improving gradually, so their
      longevity is increasing faster. In the context of the investigated problem the
      most important results were obtained from the last ten years. These results
      indicate that healthy lifestyle prolongs life.

PMID- 12183973
TI  - [Plasma level of interleukin-6 and interleukin-8 in the elderly].
AB  - It is believed that changes in the serum level of cytokines (e.g. IL-6) are
      natural consequence of physiological aging. On the other hand, increased level of
      proinflammatory cytokines (Il-6 and IL-8) occurs during inflammation. The aim of
      the study was to estimate serum levels of IL-6 and IL-8 to check if the possible
      increase in IL-6 in elderly is caused by diseases rather than by aging. The study
      involved 30 healthy elderly (Group B: age 71.1 +/- 5.5 years; range 65-89 year)
      and 29 healthy young subjects (Group K: age 27.0 +/- 4.2 years, range: 21-37
      years). In every subject serum level of IL-6 and IL-8 was assessed with
      immunoassay techniques using ELISA. The amount of subjects with the detectable
      level of IL-6 was comparable in both in group B and K (38.5% vs. 27.6%). The IL-6
      level was almost 5 times higher in older group but the difference was not
      statistically significant (10.89 +/- 22.65 vs. 2.17 +/- 4.94). Similarly, the
      amount of subjects with the detectable level of IL-8 was comparable in both in B
      and K group (20.7% vs. 18.2%) and the IL-8 level was almost 5 times higher in
      older group vs. younger one but the difference was not statistically significant
      (9.61 +/- 20.89 vs. 2.65 +/- 6.09 pg/ml). In both studied groups, subjects with
      detectable level of IL-6 (Group B1 and K1, respectively) had also higher IL-8
      level in comparison to subjects with non-detectable IL-6 (Group B2 and K2) (B1:
      18.06 +/- 27.15 pg/ml, B2: 4.33 +/- 14.43 pg/ml, p = 0.052 and K1: 7.65 +/- 8.69
      pg/ml, K2: 0.74 +/- 3.41 pg/ml, p < 0.01). The amount of subjects with detectable
      level of IL-8 was 40% in Group B1 vs. 12.5% in Group B2 and 50% in Group K1 vs.
      4.5% in Group K2 (p < 0.02). In conclusion, our study showed that increased level
      of IL-6 in elderly seems to reflect the diseases rather than aging itself.

PMID- 12183974
TI  - [Renal replacement therapy in the elderly patients in the Gdansk Pomeranian
      region].
AB  - Aging of population is a common phenomenon all over the civilized world. It
      results in increasing number of aged patients with end-stage renal disease. We
      analysed patients over 65 years who have been qualified for renal replacement
      therapy (RRT) since 1997. From that time age was no longer barrier for RRT in
      Pomerania region. Number of aged patients starting RRT raised systematically and
      achieved 61 pts in 2000. It was 25% of all starting this therapy in our region.
      In this period we observed changes in the causes of primary renal diseases:
      diabetic nephropathy raised from 15 to 27.8%, but hypertensive nephropathy
      unexpectedly was stable at 5%. Most of elderly patients qualified for RRT lived
      in town--74.6%. It means that many of them living in rural areas did not have
      adequate nephrological care and probably some of them have not been qualified for
      RRT. Late referral in this group is still a great problem. Many patients have
      never been referred to nephrologist before starting RRT. In majority of those
      cases no definitive diagnosis of ESRD was established. At present we are aiming
      at international standards and patients are started on RRT with lower level of
      serum creatinine than earlier. Increasing number of patients with diabetic
      nephropathy and in advanced age will require great effort both from nephrological
      community and health care system.

PMID- 12183975
TI  - [Early results of surgical coronary revascularization in patients 65 years and
      older].
AB  - 276 patients aged 65 years or more, who underwent coronary artery bypass grafting
      in the Department of Cardiac Surgery, Medical University of Lodz in 1999 and
      2000, were assessed. The analyzed group consisted of 193 men (69.93%) and 83
      women (30.07%). The mean age of the patients was 69.14 years (+/- 3.42, age range
      from 65 to 79 years), 18 (6.52%) patients were in the first functional class of
      CCS classification, 55 pts (19.93%) in the second, 106 pts (38.41%) in the third
      and 97 pts (35.14%) in the fourth class. 87 patients (31.52%) had no history of
      myocardial infarction, 137 pts (49.28%) had a history of 1 infarction and 53 pts
      (19.2%) of 2 or more myocardial infarctions. 68.12% of patients smoked
      cigarettes. Arterial hypertension was observed in 176 pts (63.77%), diabetes
      mellitus in 50 pts (18.11%), chronic renal failure in 10 pts (3.62%), a history
      of stroke in 8 pts (2.9%), peptic ulcer in 42 pts (15.22%). Left ventricular
      ejection fraction below 30% was observed in 16 (5.8%) patients. 10 pts (3.62%)
      underwent coronary angioplasty and in 26 pts (9.42%) critical stenosis of the
      left main stem was observed. All patients were operated on cardiopulmonary bypass
      and myocardial protection was obtained by the use of cold crystalloid cardioplegy
      solution based on St. Thomas Hospital formula. 224 patients (81.16%) were
      operated electively. In early postoperative period the following complications
      were observed: death--35 (12.68%), low cardiac output syndrome--84 (30.43%), need
      of use of intraaortic contrapulsation--31 (11.23%), perioperative myocardial
      infarction--44 (15.94%). Respiratory complications were observed in 83 pts
      (30.07%), neurological complications in 7 pts (2.54%), acute renal failure in 25
      pts (9.06%), intestinal bleeding in 5 pts (1.81%). Rethoracotomy was necessary in
      12 of the operated (4.35%). Currently the age of a patient is considered as one
      of many risk factors and should not be treated as a contraindication to surgical
      revascularization procedure. In the analyzed material mortality correlated with a
      number of risk factors. It is to remember that the elderly have higher prevalence
      of coexisting diseases and that is why their exposure to the perioperative
      complications is also higher.

PMID- 12183976
TI  - [Coronary artery bypass grafting in the elderly: early results].
AB  - Indications for CABG (coronary artery bypass grafting) procedures are on the rise
      with ageing population. Because in the world literature there is not consensus on
      the elderly patients operative risk estimation we have conducted a retrospective
      analysis of 300 consecutive patients treated at Cardiac Surgery Department of
      Bialystok University Centre. The postoperative mortality and morbidity rates were
      assessed in an each case. 103 patients over 65 and 197 younger patients were
      included to the study. An operative risk was assessed according to EuroSCORE
      protocol and was higher in the elderly group. Strangely enough, this was not
      accompanied by higher mortality and morbidity rates, which were rather similar in
      the two groups. A female gender and an inclination to gastrointestinal bleeding
      were the independent risk factors in the elderly group. Probably diabetes
      mellitus is to be held for the higher mortality rate amongst them. In conclusion,
      the results of the presented investigation suggest that a biological and not a
      chronological age is essential in the qualification for CABG procedures.

PMID- 12183977
TI  - [Early results of aortic valve replacement in patients 65 year and older].
AB  - 30 patients aged 65 years or more, who underwent aortic valve replacement in the
      Department of Cardiac Surgery, Medical University of Lodz in 2000, were assessed.
      This group consisted of 19 women (63.3%) and 11 men (36.7%). The mean age of the
      patients was 71.83 years +/- 3.76, age range from 66 to 78 years. The analysis of
      preoperative clinical state of the patients revealed prevalence of diabetes
      mellitus in 23 pts (76.7%), chronic bronchitis in 4 pts (13.3%), arterial
      hypertension in 8 pts (26.7%), pulmonary hypertension in 8 pts (26.7%), atrial
      fibrillation in 4 pts (13.3%), ventricular arrhythmia in 13 pts (43.3%) and
      cigarette smoking in 8 pts (26.7%). The mean left ventricular ejection fraction
      was 50.8% (+/- 8.12%, from 31% to 64%). All patients before aortic valve
      replacement procedure underwent coronary angiography. All patients were operated
      on cardiopulmonary by-pass and myocardial protection was obtained by the use of
      cold crystalloid cardioplegy solution based on St. Thomas Hospital formula. 7
      patients (23.3%) underwent myocardial revascularization procedure simultaneously.
      In early postoperative period the following complications were observed: death--2
      (6.67%), low cardiac output syndrome--4 (13.33%), need of use of intraaortic
      contrapulsation--3 (10%), need of use of inotropic agents--13 (43.33%),
      respiratory failure with the need of prolonged intubation--8 (26.67%), acute
      renal failure--2 (6.67%), stroke--1 (3.33%), need of temporary cardiac pacing--4
      (13.33%), need of rethoracotomy--2 (6.67%). The results of aortic valve
      replacement procedures in patients over 65 years age good, in spite of prevalence
      of number risk factors in these patients. The high rate (23.3%) of patients
      requiring simultaneous myocardial revascularization is remarkable. The age of a
      patient should not be treated as a contradiction to the cardiac surgery.

PMID- 12183978
TI  - [Early results of mitral valve replacement in patients 65 years and older].
AB  - 36 patients aged 65 years or more, who underwent mitral valve replacement in the
      Department of Cardiac Surgery, Medical University of Lodz in 2000, were assessed.
      This group consisted of 22 women (61.1%) and 14 men (38.9%). The mean age of the
      patients was 68.5 years (+/- 2.96, age range from 65 to 76 years). The analysis
      of preoperative clinical state of the patients revealed prevalence of diabetes
      mellitus in 19 pts (52.78%), chronic bronchitis in 9 pts (25%), arterial
      hypertension in 14 (38.89%), pulmonary hypertension in 21 pts (58.33%), atrial
      fibrillation in 25 pts (69.44%), ventricular arrhythmia in 2 pts (5.56%) and
      cigarette smoking in 15 pts (41.67%). The mean left ventricular ejection fraction
      was 48.89% (+/- 9.26, from 30% to 70%). All patients were operated on
      cardiopulmonary by-pass and cardioprotection was obtained by the use of cold
      crystalloid cardioplegy solution based on St. Thomas Hospital formula. 6 patients
      (16.67%) underwent myocardial revascularization procedure simultaneously. In
      early postoperative period the following complications were observed: death--6
      (16.67%), low cardiac output syndrome--5 (13.89%), need of use of intraaortic
      contrapulsation--2 (5.56%), need of use of inotropic agents--9 (25%), respiratory
      failure with the need of prolonged intubation--4 (11.11%), acute renal failure--4
      (11.11%), stroke--2 (5.56%), need of temporary cardiac pacing--5 (13.89%), need
      of rethoracotomy--1 (2.78%). The results of mitral valve replacement procedures
      in patients over 65 years are less satisfactory than those of aortic valve
      replacement procedures in the same age group, however deaths considered patients
      with number of risk factors. The older age of the patients should not be treated
      at the moment as a contradiction to the cardiac surgery, but should be considered
      as a one of many risk factors.

PMID- 12183979
TI  - [Perioperative assessment of body temperature in elderly patients during thoracic
      surgery].
AB  - Within the last years there is observed the increase in number of elder patients
      operated in planned terms. Perioperative disorders of thermoregulation are
      strongly expressed in the group of patients, and the number of complications
      rises significantly during inadvertent perioperative hypothermia. The aim of this
      study was estimation of body temperature in patients subjected to thoracosurgical
      operations. The study was performed in 23 patients older than 65 years, which
      were divided into 2 groups. In the group I (12 persons) we used usual methods of
      heat loss prevention. In group II there were used: passive methods of protection
      against heat loss as well as Hotline blood and fluids warmer with the possibility
      of intravenous fluids warming. The body temperature was estimated every 30
      minutes. The temperature detectors were located on plantar surface of hallux and
      in nasopharynx. We observed statistically significant decrease in body
      temperature values in group I. We conclude that there is the necessarity of the
      using of accessory methods of heat loss prevention in elder patients subjected to
      thoracosurgery.

PMID- 12183980
TI  - [Hypertension in the advanced old aged: prevalence and treatment in comparative
      urban and rural survey].
AB  - Hypertension is a serious medical, social and economical problem. It is accepted
      that high blood pressure is one of the major risk factors of all kinds of
      cardiovascular diseases. The aim of the study was to estimate the prevalence of
      hypertension and evaluate the difficulties with antihypertensive treatment in the
      rural and urban community dwelling elderly in advanced old age. The survey was
      carried out, as a screening, in systematically sampled 463 people 75 years old
      and over, coming from area served by primary health units (230 in urban area-
      Bialystok and 233 in rural area--Sokolka). Estimation of blood pressure (single
      measure) and medical anamnesis concerning earlier diagnoses and pharmacological
      treatment was made in proband's home by general practitioner or community nurse.
      The diagnosis of hypertension was established according to the WHO-ISN criteria.
      RESULTS: In general 49.1% of the elderly in urban and 70.4% in rural area had
      elevated systolic or/and diastolic blood pressure independently on
      antihypertensive medication; significantly more frequent in female than in male.
      32% of the elderly in urban and 22% in rural area had normal blood pressure
      without antihypertensive treatment ("healthy"), whereas respectively 19% and 7%
      had normal blood pressure with antihypertensive treatment. 21% of persons in
      Bialystok city and 38% in Sokolka had elevated high arterial pressure and hadn't
      any antihypertensive treatment. The results of the study confirm the high
      prevalence of hypertension in elderly population, higher in rural than urban
      area. Therapy of hypertension in studied group was ineffective in most of the
      hypertensive patients, mainly in neglected rural area. The differences between
      urban and rural samples can be partly explained by socio-demografic
      characteristic of the two studied population.

PMID- 12183981
TI  - [Some aspects of pharmacotherapy among the eldest living in veterans' homes].
AB  - We have described some aspects of pharmacotherapy among 89 residents of veterans
      homes, 20 men and 69 women, aged between 90 to 103 (average 92.3) years old. Half
      of the residents strictly complied with the doctor's instructions whereas 22%
      used to either discontinue taking the drugs or decrease the dosage according to
      their own will. Polypragmasia was not very common. About 21% patients used to
      take from 4 to 7 drugs whereas 9% from 8 to 10 medicines. Guiding instructions of
      International Medical Associations regarding pharmacotherapy were initiated on a
      very small scale for patients over 90 years of age. Due to that, the therapeutic
      procedures were highly incompatible with present standards.

PMID- 12183982
TI  - [The chronic DIC associated with the neoplastic disease in patients of an
      advanced age].
AB  - The analysis included 80 patients (48 men and 32 women) aged 65 to 87 years,
      treated because of cancer of the stomach (34 causes) or of the large bowel (46
      causes). In all the patients as well as in a control group made up of persons who
      were treated because of non-neoplastic diseases of the gastrointestinal tract the
      determinations were conducted of selected coagulological parameters: fibrinogen
      and D-dimer concentration, antithrombin III (AT III) activity, kaolin-cephalin
      index (APTT), prothrombin (PT), thrombin time (TT) and number of thrombocytes in
      the blood. The analysis of the results obtained showed that hemostasis
      disturbances of a chronic DIC character occur in 82.5% of persons of an advanced
      age ill with a cancer of the stomach or of the large bowel.

PMID- 12183983
TI  - [The efficacy of the Helicobacter pylori eradication in people of an advanced
      age].
AB  - In a group of 112 patients aged 65 to 72 years with chronic gastritis (48
      persons), a peptic ulcer (30 persons), a duodenal ulcer (34 persons)
      bacteriological examinations were conducted aiming at determining the sensitivity
      to antibiotics of Helicobacter pylori (H. pylori) strains isolated from the month
      (gingival pockets), the stomach or duodenal mucous, from stool samples and from
      the skin of the hands. The sensitivity to antibiotics was tested with the
      diffusive-disc method taking into consideration 23 chemotherapeutic agents. It
      was shown that with the use of single antibiotics the chance of efficiently
      elimination the H. pylori infection from the area of the whole alimentary canal
      (month, stomach, duodenum, large bowel) amounted to 14.3-35.7% depending on the
      chemotherapeutics used, where with the use of a two-medicine therapy
      (metronidazol + amoxycillin) it increased to 42.9%. This means that in people of
      an advanced age the chemotherapy carried out with the aim of liquidating the
      infection in the stomach or duodenum mucousa creates possibilities for the H.
      pylori infection to persist in other parts of the alimentary canal ranging from
      64.3 to 85.7%. This way the patient treated may then undergo self-infection as
      well as be a source of infection for other persons.

PMID- 12183984
TI  - [The disturbance of the magnesium management in patients in grave clinical
      status].
AB  - The analysis included 46 patients (27 men and 19 women), aged 41 to 76 years, who
      required intensive medical care because of a grave clinical state. In all af
      them, as in a group of patients treated because of illnesses identical to those
      of the basic group but not requiring intensive medical care (CG), as well as in a
      reference group (RG)--blood donors, the determinations were conducted of the
      magnesium concentration in the serum with the flame atomic absorptive
      spectrometry method. It was confirmed that in the patients in grave clinical
      state the average concentration in the serum of that element was statistically
      significantly lower that in the other groups (CG and RG). The average magnesium
      concentration also differs statistically really between the CG and RG. A critical
      value was also determined of the magnesium concentration in the serum raising
      5.78 micrograms/ml, which may be the prognosis of the metabolic disturbances
      leading to a grave clinical state.

PMID- 12183985
TI  - The importance of determination of magnesium concentration in the serum of
      patients with cancer metastases to the liver.
AB  - The study was carried out on 48 patients (26 male and 22 female), aged 52-76
      diagnosed as having cancer metastases to the liver. The serum level of magnesium
      in the studied group and also in two other groups (the first consisting of 48
      blood donors and the second of 50 patients suffering from cancer of a non
      disseminated nature) was measured by the flame atomic absorption
      spectrophotometric method. The results of the study showed that cancer metastases
      to the liver significantly decrease the mean level of magnesium in serum compared
      to the other two groups. It was shown that a magnesium level below 12.76
      micrograms/ml in cancer patients increased the risk of cancer metastases to the
      liver.

PMID- 12183986
TI  - [Vascular dementia and systemic changes].
AB  - The aim of the study was to evaluate risk factors of atherosclerosis and extra
      cerebral target organ damage in patients with hypertension and vascular based
      mild memory disorders. A group of the study included 20 persons at age of 54-75
      (8 males and 12 females) with mild vascular dementia (20-25 pts in MMSE, 22.8 +/-
      1.73) with treated mild hypertension. A diagnosis of vascular dementia was
      confirmed in MRI by two independent experts. All examined patients presented
      multiinfarction changes in central nervous system as a cause of dementia. The
      study protocol contained present history, physical examination, 24-hour
      ambulatory blood pressure monitoring (ABPM), ECG, biochemical tests: total
      cholesterol, HDL-Ch, LDL-Ch, triglycerides, glucose, urea, creatinine plasma
      levels and urine test for microalbuminuria. In part of the study group (55%)
      echocardiography with posterior wall (PW) thickness and ejection fraction (EF)
      evaluation was performed. In the analysed group mean 24-hour blood pressure
      values were not elevated (SBP 130.8 +/- 15.8 mm Hg and DBP 77.6 +/- 9.2 mm Hg at
      day, respectively 121.6 +/- 17.1 mm Hg and 68.2 +/- 11.6 mm Hg at night). No
      significant (> 10%) nocturnal SBP decrease was observed, however DBP fall was
      noticed. Either total cholesterol (n < 5.2 mmol/l) or LDL-Ch (n < 3.5 mmol/l)
      plasma levels were increased in patients with vascular dementia and ranged
      respectively 5.8 +/- 0.9 and 3.7 +/- 0.9 mmol/l, HDL-Ch and triglycerides levels
      remained normal (respectively 1.7 +/- 0.5 and 1.5 +/- 1.1 mmol/l). Mean urea and
      creatinine levels were maintained in normal range (urea 5.8 +/- 1.7 mmol/l,
      creatinine 75.5 +/- 15.1 mumol/l). In a part of study group (35%)
      microalbuminuria was presented (urine albumine > 20 mg/l). In majority of
      patients with hypertension and vascular dementia a few risk factors co-existed.
      No systolic blood pressure decrease observed at night in 24-hour blood pressure
      monitoring, though normal mean values, can play an important role in vascular
      abnormalities progression.

PMID- 12183987
TI  - [Determinants of dementia in the advanced old age elderly].
AB  - The development of civilization and progress in medicine made the prolongation of
      the life span and increased share of the advanced old age people in the
      population. The consequence of this process is growth in frequency of diseases
      related to age including dementia. However diagnosis of cognitive impairment is
      still difficult and it makes some problems in an everyday medical practice. The
      aim of this report is to define main and significant determinants of dementia
      basing on the MMSE scale. This could make it easier to suspect the cognitive
      disorders to make indepth diagnosis and to start earlier therapy. The sample
      consisted of 124 community dwelling persons 75-year old and over. 64 of them were
      mildly, moderately or severely demented according to Katzman scale administered
      previously and 60 were intellectually intact. The both groups of persons were
      tested with MMSE. Geriatric Depression Scale, ADL scale (EASY-Care questionnaire)
      and short internal and neurological examination. The multiple regression model
      were used, where dependent variable was the MMSE score and independent variables
      social-demographic data, ADL and GSD scales and data from interview and medical
      examination. 72 variables were included to the model and 39 of them were
      significantly connected with cognitive impairment. The valid factors explained
      dementia in 78.7% (adjusted R2 = 0.787). The strongest connection was found with
      (1) an ignorance of own date of birth, (2) low education level, (3) behaviour
      disorders and (4) an advanced old age. These determinants, including difficulties
      with handling own money, have explained dementia in 57%. The presence such
      symptoms could make easier to suspect the cognitive disorders, to make in-depth
      diagnosis, and to start earlier therapy.

PMID- 12183989
TI  - [Psychological examinations of the personality of patients with cardiac syndrome
      X].
AB  - 76 patients with chest pain including 27 men and 49 women from 25 to 75 (mean
      49.96 +/- 11.36) years old, were examined by means of the psychological test. All
      the patients showed positive exercise test and no changes in coronary arteries.
      Psychological test was done by the use of personality--MMPI--2 (Minnesota
      Multiphasic Personality Inventory) test and depression was diagnosed by GDS
      (Geriatric Depression Scale) by J. Yesavage--15 questions version. The highest
      mean values in MMPI--2 were obtained in neurotic scales. It indicates that
      emotional disorders in these patients emerge as hypochondriacal and hysterical
      neurosis. In 37 patients (48.7%) neurotic scales showed typical "conversion
      valley" and these who show such a change in MMPI--2 talk mainly about somatic
      complains (not psychological) during long-term stress situation. In 25 (32.9%)
      patients single psychological symptoms of depression could be seen and depression
      episodes were diagnosed in 17 patients (22.4%).

PMID- 12183988
TI  - [Impaired cognitive function as an independent risk factor for the in-hospital
      mortality in the elderly with chronic heart failure].
AB  - Heart failure (HF) and impaired cognitive function are frequent causes of
      hospitalization in elderly patients. Independently, both clinical syndromes are
      associated with increased mortality. The aim of the study was to evaluate the
      influence of impaired cognitive function on in-hospital mortality in old patients
      with HF. A modified Mini-Mental State Exam (MMMSE) was performed in 598
      consecutive patients (65-102 years old; 355 female) with heart failure. All
      patients were stratified into low (6.3 +/- 1.2 points), medium (19.7 +/- 4.7
      points) or high (29.1 +/- 2.1 points) tertile group according to MMMSE results.
      Total in-hospital mortality was 52.0% in the lowest, 34.2% in the medium and
      15.1% in the highest tertile (Pearson Chi-square p < 0.0001 for trend). The
      comparison of in-hospital mortality between tertiles of MMMSE was done with the
      use of logistic regression adjusted to age, sex, and the presence of diabetes
      mellitus, renal failure and anemia. Comparison of in-hospital mortality between
      patients from the lowest tertile of MMSE with the highest one revealed that odds
      ratio was 5.93 (95% CI: 3.58-9.80; p < 0.0001) whereas it was 2.67 (95% CI: 1.60
      4.67; p = 0.0002) for patients from the medium tertile. The obtained results show
      that the worse cognitive function is, the worse in-hospital prognosis can be
      observed in older patients with HF. Moreover, it also suggests that impaired
      cognitive function may be an independent risk factor for mortality in elderly HF
      patients.

PMID- 12183990
TI  - [Analysis of psychological examination results for patients over 60 years of age
      treated in the Department of Clinical Toxicology CM UJ after suicide attempts].
AB  - Psychological examination done in the Toxicological Department covers almost all
      patients treated after suicidal attempts. Elder people constitute a small
      percentage of this population. Our observation shows, that this percentage is
      growing in recent years. This analysis covers 188 patients over 60 years of age.
      Involvement of a psychologist was not only diagnostic but also therapeutic.
      Important part of the treatment included a session with patient's family and
      effort targeted to help patients for whom coming back to their previous
      environment could present life threatening danger.

PMID- 12183991
TI  - [Suicide attempts by self-poisoning among the elderly].
AB  - The aim of the study was to present suicidological problems in the elderly. The
      investigation assessed patients treated for self-intoxication in the Department
      of Toxicology of Collegium Medicum, Jagiellonian University in Cracow. Medical
      documentation of the entire population of subjects aged over 65 and hospitalized
      in the years 1999-2001 was examined from the point of view of demographic and
      clinical factors. The examined population consisted of 68 subjects including 20
      males and 48 females ranging in age from 65 to 90 years (mean age = 72.6). The
      majority of subjects were retired and, in many cases, lived alone. The majority
      of female subjects were widows living in Krakow or in small towns or villages
      around Krakow. A significant number of subjects had been undergoing psychiatric
      treatment or even repeated hospitalization prior to the suicide attempt. A
      significant percentage had suffered from severe somatic diseases. For 55 of the
      subjects (79.7%), it was the first suicide attempt, and for 14 subjects (20.3%)-
      a repeated one. The drugs most frequently used in the attempts were psychotropic,
      cardiological and mixed-type drugs. The assessment included the state of
      consciousness and the degree of intoxication on the subjects' admission to
      hospital. The mean duration of hospitalization was 13.7 days. The most frequently
      determined somatic diseases were hypertension (33.3%) and coronary artery decease
      (30.4%), atherosclerosis (15.9%) and diabetes (10.1%). In the process of a
      complex diagnostic and therapeutic procedure, the mental state of the patients
      was assessed. Depressive disorders (reactive) and endogenic depression
      (affective) were recognized in 51 subjects (73.9%). Organic brain disorders,
      often with dementive signs, were detected in 44 subjects. Schizophrenia was
      recognized in only a small percentage of subjects (5.8%). The description of the
      data indicate a close connection between depression and social factors in the
      case of the elderly. Therefore, an adequate treatment of depression should be
      give priority in programs for preventing suicide among the elderly.

PMID- 12183992
TI  - [Completed suicide and depression in the elderly].
AB  - The aim of the study was to present problems of completed suicide and depression
      in the elderly. Postmortem examinations were conducted in the Institute of
      Forensic Medicine of the Jagiellonian University. The analysis included cases of
      completed suicide in adults, from which all the cases of individuals aged over 65
      who in the years 1998, 1999, and 2000 committed suicide within the area of Krakow
      the City were selected for the present study. The examined group consisted of 92
      individuals ranging in age from 65 to 89 years, including 34 females and 58
      males. The mean age was 72.5 for the entire group. 44.5% of the subjects had
      resided in a big city (Krakow); the remainder of the group had resided in
      villages and towns around Krakow. 57.6% of the subjects committed suicide by
      hanging, 16.3%--by falling from a height, and 13%--by drowning. In the majority
      of cases (77.2%), the suicide was committed at home. In 17 cases (18.5%), the
      post mortem revealed the presence of alcohol. As regards somatic diseases in the
      examined population, the data from the anamnesis (often incomplete) indicate
      frequent occurrence of cardiovascular diseases. 43.5% of the subjects, who
      committed suicide, had been treated for mental disorders, mainly for depression,
      organic brain disorders, and alcohol addiction. 17 of the subjects (18.5%) had
      previously attempted to commit suicide. The above results indicate that a typical
      representative of the elderly committing suicide is a septuagenarian residing in
      the country or in a small town, and most typically committing suicide by hanging
      at home. The attention must be paid to the high number of mental disorders,
      especially depression, detected among both male and female subjects. The close
      relation between suicide and depression in the elderly is an important guideline
      on suicide prevention programs and therapy of psychogeriatric patients.

PMID- 12183993
TI  - [The completed and attempted suicide in Krakow: similarities and differences].
AB  - The study presents the results of the interdisciplinary research conducted on the
      basis of cooperation between the Institute of Forensic Medicine, the Department
      of Clinical Toxicology, and the Clinic of Psychiatry in Krakow. The aim of the
      research was to determine similarities and differences between attempted and
      completed suicide from the point of view of socio-demographic and clinical
      traits. The authors analysed 220 cases of completed suicide committed in Krakow
      and its environs in the year 2000. The material presented in the study was based
      on the archive data from post mortem examinations conducted in the Institute of
      Forensic Medicine in Krakow. The sample consisted of 177 males and 43 females
      ranging in age from 13 to 89 years. The mean age was 43.6 years for the entire
      group, 42 years for males and 50 years for females. The majority of subjects were
      males, either unemployed, or pensioners. A similar tendency was observed in the
      group of female subjects. Mental disorders and alcoholic addiction in anamnesis
      were discovered in a significant number of cases, both in the group of males and
      in the group of females. Subjects, in whom serious somatic diseases had been
      detected, constituted a separate group of cases. According to the archive data,
      in the last century, suicide was most frequently committed by hanging. Similarly,
      in the sample examined, in 133 cases, suicide was committed by hanging. In 37% of
      cases, the level of alcohol in the suicides' blood was between 0.5 and 3 or more
      g/L. In 2000/2001, within the analogical period of 12 months, the group of 200
      patients after a suicide attempt by drug intoxication was examined in the
      Department of Clinical of Toxicology Jagiellonian University College of Medicine.
      This group included 49 males and 150 females, ranging in age from 18 to 79 years
      (mean age 35). The examination was conducted by means of structured investigation
      and medical documentation. Contrary to completed suicide, in the group of suicide
      attempters, females outnumbered males. Young people under thirty, living in a
      large city, possessing elementary or secondary education, and either unemployed,
      or pensioners, constituted the majority of the examined group. A significant
      percentage of females was divorced and lived with their children only. The
      majority of the examined population of suicide attempters had used alcohol during
      the attempt, had suffered from depression, personality or behavioural disorders,
      had undergone psychiatric treatment, or had had cases of suicide among their
      friends or relatives.

PMID- 12183994
TI  - [Falls in the elderly: analysis of potential risk based on observations in 1994
      2001].
AB  - In medicine a fall is commonly construed as a sudden and totally accidental loss
      of postural balance, be that whilst walking or pursuing any other physical
      activities, in result of which a victim falls directly onto the ground, floor, or
      any other low-sited surface area. Frequency of falls in the elderly breaks down
      into 33% in the outpatients, 20% in the hospitalised patients and 45% in the
      nursing home residents. Data regarding the actual frequency of falls often
      misrepresent the facts, as most falls do not result in severe complications,
      although frequently enough facilitate development of post-fall syndrome and in
      due course in manifest deterioration of patients' overall mobility, thus making
      them even more prone to prospective falls. Around 10-15% of falls results in
      serious, life-threatening trauma. Immobilisation of a patient in the wake of a
      serious fall brings about a potential threat of venous thrombosis, pulmonary
      embolism, dehydration, muscular contracture and bed sores. Consequently, more
      frequent and prolonged hospitalisation is required, whereas a patient becomes
      steadily more care-dependent. By far the most frequent consequences of falls are
      bone fractures (50%), the ones sustained within the upper femoral bone area
      considered the most serious. Mortality resultant from post-fall complications
      tends to increase significantly with every decade of age. In full consideration
      of the above issues the present study aimed to assess the potential risk of
      accidental falls in the elderly, and therefore the falls sustained by 571
      residents (aged 68-93 years) of two nursing homes in Krakow throughout 1994-2001
      were subject to detailed analysis. The data yielded comprehensive information on
      the accompanying circumstances (i.e. specific location, timing, prevalent
      situation) within each one of the studied groups, thus facilitating development
      of the appropriate preventive measures. Studies comprehensively addressing the
      issue of accidental falls in the elderly and the attendant medical care costs
      sustained by the public health system are still very scarce in Poland, although
      the problem definitely merits further studies and an in-depth investigation,
      especially in consideration of the on-going restructuring within the country's
      medical service sector.

PMID- 12183995
TI  - [Rehabilitation as component of falls prevention program in the elderly].
AB  - Accidental falls tend to be anxiously perceived by a steadily increasing number
      of elderly persons as a definite symptom of ageing, instilling them with fear of
      becoming invariably care-dependent in the wake of having sustained a serious
      fall. Minimising the risk of accidental falls and complications resulting from
      them depends upon gaining a good insight into the accompanying circumstances, all
      with a view to establishing the nature of potential risks and developing a series
      of effective measures aimed at their prevention. Detailed reconstruction of the
      accompanying circumstances is a practical way of establishing all key risk
      factors and facilitates subsequent monitoring of patients' mobility, as well as
      effectively safeguards them against taking any undue risks. Since the
      observations made by the present authors and other investigators alike gave ample
      grounds to believe that rehabilitation constituted an essential component in any
      fall prevention programme, the impact of a specific rehabilitation regimen on the
      incidence of falls amongst the residents of STYRIA Municipal Nursing Home,
      Chorzow, was assessed with a view to establishing the pertinent correlations. The
      inclusion criteria required that a resident must have sustained at least one
      accidental fall in the period preceding the actual study (pursued in 1999-2000).
      Out of 61 residents 28 (aged 68-91) were eventually enrolled. The study focused
      principally upon assessing the risk of accidental falls and individual functional
      abilities. A three-month long rehabilitation programme embraced, e.g. individual
      counseling on the potential risk of falls, kinesitherapy and practical exercises
      in a safe change of posture. Comparative analysis was pursued with the aid of a
      non-parametric Wilcoxon test. The results confirmed the statistical significance
      of all parameters under investigation, which in turn gave ample grounds to
      believe that an appropriately designed rehabilitation programme might be
      effectively instrumental in fall prevention. This conclusion was further
      corroborated by the nursing reports, attesting to the perceptibly lesser
      frequency of accidental falls amongst the residents. There seems to be overall a
      substantial potential for gaining tangible benefits without the public health
      sector incurring undue financial burdens, whereas steady ageing of the country's
      population and the attendant increase of health care expenditure should prove an
      effective stimulus to launching comprehensive preventive schemes.

PMID- 12183996
TI  - [Effect of age on medical complications in acute carbon monoxide poisoning].
AB  - The aim of the study was to compare the frequency and clinical course of carbon
      monoxide poisonings (early or delayed medical complication or death) regarding
      the age of patients. All symptoms which were not diagnosed on admission but
      occurred during first three weeks after carbon monoxide exposure were stated as
      early complication and after three weeks as delayed. A full recovery was noted in
      61.8% of patients younger than 60 and only in 28.4% of patients older than 60
      years (p < 0.01). The frequency of medical complications and number of deaths
      were significantly higher in the group of older persons. The toxic myocardial
      injury followed by respiratory tract inflammations were predominant early
      complications and a psychoorganic syndrome was a predominant late complication in
      the oldest group of CO poisoned patients.

PMID- 12183997
TI  - [Acute poisonings in Poland during the period 1997-1999. An analysis of files
      from the Krakow Poison Information Center].
AB  - This work analyses the 1997-1999 data received from Polish poison units at
      Gdansk, Krakow, Lublin, Lodz, Poznan, Rzeszow, Tarnow, Sosnowiec, Warszawa,
      Wroclaw on patients hospitalised there and patients treated at other hospitals
      but consulted by specialists of those centres. The analysis shows that drugs
      constituted the most frequent cause of the poisonings (over 45% all poisonings).
      Poisonings with: alcohols accounted for 17.6%, gases (primarily by carbon
      monoxide) for 5.3%, pesticides for 4.5%, substances of abuse for 4.1%, and with
      organic solvents for 4.0% total poisonings. Suicidal poisonings constituted about
      36% total poisonings, accidental over 25%, poisonings resulting for street-drugs
      and alcohol abuse over 23%, chemical emergency or fire 1%, while occupational
      poisonings constituted only 0.9% total poisonings. In 1997-1999, the highest
      numbers of deaths were recorded after intake of: drugs (102), ethylene glycol
      (39), alcohols (49, including 16 after intake of methanol and 33 after intake of
      ethanol), pesticides (15 deaths).

PMID- 12183999
TI  - [Analysis of the cases of poisoning among elderly patients based on the material
      of St. Lukasz Provincial Hospitals in Tarnow in the period 1996-2001].
AB  - We present the statistical data relating to the cases of poisoning in persons
      over 65 years of age, admitted to our hospital in period of the last 6 years. We
      refer these data to the population of younger persons, looking for differences
      and similarities. We also discuss briefly substantial limitations and
      characteristics of the proceedings, in particular the therapeutic management, in
      this group of patients.

PMID- 12183998
TI  - [The pattern of poisonings with chemical compounds in Krakow inhabitants
      hospitalized at the Department of Clinical Toxicology of the Jagiellonian
      University Medical College in 1997-2001 in relation to age].
AB  - The pattern of poisonings in patients hospitalised in the Department of Clinical
      Toxicology Jagiellonian University Medical College in 1997-2001 was presented in
      the study. The analysis includes 17,931 patients: 6,016 (33.5%) women and 11,915
      (66.4%) men. The rate of patients between 20-39 years old was highest in all the
      analysed year, however downward trend was noticed. The upward tendency was noted
      in older group of poisoned patients. A suicidal poisonings were mostly common in
      1998 and 1999 in the youngest and oldest groups: 37.1%, 37% in 1998, and 25.5%,
      22.2% in 1999 respectively. The medication drugs were the most common cause of
      acute poisoning only in the group of adolescent patients. Ethyl alcohol was the
      common cause of poisoning in adult groups. The highest rate of ethanol
      intoxication was noted in patients between 40 to 59 years old. A 89 lethal
      intoxication were noted in analysed period. The average mortality rate was low
      (0.5). A medication drugs (30.4%) followed by ethanol (17.4%), carbon monoxide
      (13%) and solvents (13%) were involved in lethal poisonings in the oldest group
      of patients.

PMID- 12184000
TI  - [Acute intoxication in patients over 65 year-olds treated in Toxicological Center
      in Poznan in the years 1997-2001].
AB  - The aim of the study was to assess the frequency of intoxication in patients over
      65 years, their motives and applied pharmaceutics. The medical reports of
      patients beyond 65 years treated in Toxicological Center in Poznan in the years
      1997-2001 were reviewed. During 5 years 4659 patients were treated, among them
      were 118 patients (2.53%) elder than 65 years. Most of the patients were females.
      Most common used drugs were benzodiazepins alone or applied with other drugs
      (antihypertensive, antidepressive, pain-relievers and ethanol). Suicidal attempts
      in course of depression were the most common cause of intoxication. In analysed
      material 6 cases of death were reported. The advanced age and coexisting disease,
      not intoxication alone were main reasons of them.

PMID- 12184001
TI  - [Cardiovascular drugs poisoning in the elderly patients hospitalized in the
      Province Poisoning Center in Lublin in the years 1995-2001].
AB  - The aim of our research was retrospective analysis of poisoning with
      cardiovascular drugs (T46 according to ICD 10 classification) in patients over 59
      years old, hospitalized in Province Poisoning Centre in Lublin, in the period
      from 1995 to 2001. There were hospitalized 288 patients at this time age, over 59
      years old. Among this 16 persons were poisoned with cardiovascular drugs (one
      accidental and 15 suicidal intoxications), and 3 of them died. Different kinds of
      cardiovascular medications were used e.g. digoxin, nitrates, hypotensive drugs
      (as single and multiplied drug poisonings). At 3 of the patients depression was
      diagnosed.

PMID- 12184002
TI  - [Benzodiazepine poisonings among elderly patients of Acute Poisoning Department
      of the Marciniak Memorial Hospital in Wroclaw in the years 2000-2001].
AB  - Acute benzodiazepines poisonings in the group of 27 elderly patients is
      discussed. Majority of patients suffer from depression and cognitive impairment.
      Compared this special group of patients with younger the prognosis is worse what
      is expressed in greater number of deaths.

PMID- 12184003
TI  - [Ventilation efficiency and nervous breathing regulation in ethanol-dependent
      persons over 50 year of age].
AB  - A ventilatory efficiency and nervous breathing regulation in ethanol dependent
      patients older than 50 years was compared to younger counterparts during
      controlled, absolute abstinence while hospitalisation in the Department of
      Clinical Toxicology. Respiratory resistance was the most differential factor:
      higher in alcoholics compared to the control group and in older alcoholics higher
      than in younger alcohol dependent patients. Similarly the occlusion pressure was
      higher in ethanol dependent persons compared to the control group. A
      normalisation of respiratory function after 9 days of absolute abstinence was
      stated in the group of younger alcoholics only. The most of respiratory pattern
      parameters did not change after the abstinence period. Only values of the
      occlusion pressure was diminished substantially.

PMID- 12184004
TI  - [Correlation between self-reported drug use and the results of hair analysis in
      detoxification and methadone treatment patients].
AB  - Hair analysis offers the possibility of revealing an individual's recent history
      of drug exposure beginning at sampling day and dating back over a period of weeks
      or months. This feature of hair analysis can be applied in clinical setting for
      monitoring drug use by addicted patients being rehabilitated. The aim of this
      study was to apply determination of major opiates and amphetamines in hair to
      confirm medical interview made by a physician in detoxification and methadone
      treatment patients. These assays used gas chromatography coupled to mass
      spectrometry (GC/MS) for opiates and liquid chromatography coupled to atmospheric
      pressure chemical ionisation mass spectrometry (LC/MS-APCI) for amphetamines.
      Most unconfirmed interview data were in the group of detoxification patients.
      Four methadone patients were negative for opiates.

PMID- 12184005
TI  - [Subjective Quality of Life in opiate-dependent patients before admission after
      six months and one-year participation in methadone program].
AB  - The aim of this study was to compare a subjective Quality of Life (QoL)
      assessment before, after six and twelve months of participating in methadone
      program. There were included 61 patients (39 males and 22 females). The SF-36
      questionnaire was used. We found that in our patients before admission to
      methadone program QoL was extremely low. After six-months participation in
      substitution therapy QoL increased significantly in seven from eight subscales of
      SF-36. During next six months QoL unexpectedly decrease, but not to prior level.
      There were not significant differences in QoL between men and women although men
      beneficiated from methadone program more than women. In our study HIV
      seropositivity hadn't influence on QoL.

PMID- 12184006
TI  - [Palliative care problems in the elderly patients].
AB  - Palliative care has rapidly developed due to increasing of cancer disease and
      ageing of society as well. Philosophy of palliative care means: holistic care,
      good quality of life as it's main goal and acceptance of death. Good palliative
      care means also that the terminally ill elderly patients should be divided into
      two groups: 1. Persons with good psychic health state (but with some specific
      features of "senile personality"); 2. Patients with psychiatric disorders
      (dementia, delirium, aggressive behavior). The prompt recognition and treatment
      of both psychiatric and psychic healthy terminally ill patients becomes very
      important to the effective and good palliative care.

PMID- 12184007
TI  - [The exposure to tobacco smoking].
AB  - The exposition to tobacco smoke is overall: in home, work and public places. For
      the examination of the presence and concentration of environmental tobacco smoke
      (ETS) in indoor environments the nicotine and respirable suspended particulates
      (RSP) are determined. A variety of biomarkers (nicotine, cotinine, thiocyanate,
      carboxyhemoglobin, protein and DNA adducts) are propose for measurement of
      exposure to tobacco smoke. The most popular is measurement of cotinine
      concentration in body fluids (blood, urine, saliva). Plasma cotinine
      concentration correlated to numbers of cigarettes smoked and to various
      biological effects of cigarette smoking and exposure to ETS. Other biomarkers as
      carboxyhemoglobin, thiocyanate, and amines and polycyclic aromatic hydrocarbons
      adduct can be also use.

PMID- 12184009
TI  - [Do the majority of senior patients with carbon monoxide poisoning suffer a
      cardiac infarction?].
AB  - The last few years have brought a real breakthrough in the approach to the
      instable coronary heart disease, understanding of its pathogenesis, diagnostics,
      differentiation and prognostication. In September 2000 the joint committees
      European Society of Cardiology and American College of Cardiology acknowledged
      the heart troponins as a golden standard in the recognition of cardiac infraction
      and proposed a new definition of infraction which replaced the WHO criteria
      binding from 1979. Due to high sensitivity and specificity, determination of the
      heart troponin makes it possible to recognize the muscle damage on a quite small
      area (small-area infraction). This will increase the number of recognitions of
      cardiac infraction and may significantly increase the frequency of recognition of
      this type of complication in patients with carbon monoxide poisoning, especially
      in a group of senior patients.

PMID- 12184008
TI  - [The other face of statins].
AB  - Clinical studies indicate that treatment with statins significantly reduces the
      incidence of myocardial infarction and death from cardiovascular diseases. Quite
      recently statins were found to exert a direct cardiovascular effect, which is
      independent on their well-known cholesterol lowering action. In this article
      current views on the role of statins in improvement of function of vascular
      endothelium are presented.

PMID- 12184010
TI  - [Usefulness of some databases in medical practice].
AB  - The following publication include results of thinking the matter over usefulness
      some computer, medical databases as well as Internet drug information resources.
      Quantity of medical software and Internet portals is not equal to quality, so it
      is necessary to order and classify medical electronic tools. It was bring
      MICROMEDEX databases system to readers attention, as a model, reference tool
      helpful in computer aided medicine.

PMID- 12184011
TI  - [Internet as a means of persuading a patient to commit a suicide].
AB  - In this article we have described 25 year-old female student of the University of
      Gdansk, treated for eight years because of depression and for four years because
      of anorexia nervosa, who to commit suicide had taken 50 tablets of carbamazepine
      (Tegretol CR a 200 mg), 30 tablets of clonazepam (Clonazepamum a 0.5 mg) and 50
      tablets of flupentixol (Fluanxol a 3.0 mg). In 1999 the patient got an internet
      (IRC) contact with a person introducing herself as a 26 year-old lonely student.
      After getting acquainted with the life history of the patient she had
      systematically encouraged the patient to commit suicide. Almost everyday she used
      to send the patient instructions regarding the best way to kill herself. On
      parent's request, after the patient regained consciousness in the Clinic, the
      case was sent to public prosecutor's office. It was found, that the person who
      urged the girl to commit suicide was a 33 year-old married woman, fascinated by
      psychology and parapsychology.

PMID- 12184012
TI  - [Repeated metallic mercury intravenous injections for doping].
AB  - In this article we described a 24 year-old patient, suffering from nephropathy of
      unknown origin, who was admitted to the Clinic after having tried to commit
      suicide for the third time by overusing tricycle antidepressant drugs (TLPD) and
      ethanol. During toxicological tests the serum TLPD level was 548 micrograms/L and
      the serum ethanol level was 2.1 g/L. His chest X-ray showed the presence of
      several metal particles of approx. 1.5 mm in diameter disseminated in both lungs,
      which could have been particles of metallic mercury. When the state of coma was
      over the patient admitted that for the past three years he had many times
      injected intravenously a small amount of metallic mercury (about 0.5 ml/dose) to
      improve his strength, speed and physical fitness. Tested serum mercury level was
      300 micrograms/L and urinary mercury excretion 500 micrograms/L/24 hours.

PMID- 12184013
TI  - [Fatal intoxication with paramethoxyamphetamine].
AB  - From August to December of the year 2000 we ascertained 7 rapid deaths because of
      acute intoxication with tablets colloquially called Ufo. There were five men and
      two women aged from 20 to 29 (average 24) years. Analytic tests showed that one
      tablet of Ufo contains 40 mg of paramethoxyamphetamine, 1.0 mg of amphetamine,
      0.05 mg of methamphetamine, 0.03 mg of 3-4-methylenedioxymethamphetamine. The
      levels of paramethoxyamphe-tamine in the blood of the deceased, determined by gas
      chromatography, were from 0.68 to 10.0 (approx. 3.2) mg/L and in the urine from
      16 to 64 (approx. 35) mg/L. The press and television campaign caused elimination
      of fatal intoxications with parametoxy-amphetamine during the last 13 months.

PMID- 12184014
TI  - [Alcohol-paracetamol syndrome: a case report].
AB  - Risk of hepatotoxicity from acetaminophen taken in therapeutic or modestly
      excessive doses is high in alcoholics and long-term alcohol users, cachexic
      patients and people taking drugs inducing acetaminophen metabolism on microsomal
      cytochromes P450. Interaction between alcohol and acetaminophen increases
      production of NAPQI--highly reactive and toxic metabolite of paracetamol.
      Elevation of transaminases activity (especially AST) and other evidence of
      hepatic injury in patient with history of both alcohol and paracetamol intake
      should be suspicied of alcohol--acetaminophen syndrome; in such cases treatment
      with intravenous acetylcysteine should be maintained as soon as possible. In
      study case of 23-year old alcoholic man admitted to Department of Toxicology in
      Poznan with symptoms of acute hepatic failure after accidental paracetamol
      overdose is presented. After 5 days long ACC infusions patient's state improved
      and 2 weeks later he left hospital in full recovery.

PMID- 12184015
TI  - [Cappuccino coffee treatment of xerostomia in patients taking tricyclic
      antidepressants: preliminary report].
AB  - 10 patients underwent a trial treatment with Cappuccino coffee. All of them (8
      university lecturers and 2 clerks) aged from 60 to 69 (average 63) years old,
      used tricyclic antidepressant because of insomnia as a monosymptomatic type of
      depression or insomnia as a dominant symptom in the course of depression. One,
      evening dose of doxepine was from 150 to 250 (average 225) mg, causing xerostomia
      next day usually between 9-15 o'clock. The five-minute--chewing of 15.0 g of
      Cappuccino coffee increased the amount of saliva, decreased xerostomia and
      improved the ability of speech. Beneficial effect of coffee lasted from 0.5 to 4
      (average about 2) hours. To the best of our knowledge there are no publications
      dealing with the positive effect of coffee in xerostomia.

PMID- 12184016
TI  - [Cardiac toxicity of carbamazepine].
AB  - Carbamazepine toxicity on cardiovascular system in the course of acute poisonings
      and long term therapy are observed rarely. It's toxic influence on action
      potential in Purkinje fibres and 4 depolarization phase expresses clinically as
      the His bundle and atrioventricular blocks especially in patients with
      cardiologic disturbances. We present case of 64-year old woman with ischaemic
      heart disease poisoned with carbamazepine who died because of severe arrhythmias
      in the course of myocardial infarction during first 24 hours of intoxication.
      Heightened awareness of high risk lethal cardiovascular complications in patients
      intoxicated with carbamazepine with history of heart diseases is needed.

PMID- 12184017
TI  - Acute poisoning with Tricholoma equestre.
AB  - Two cases, mother and her son, suffering from acute poisoning with Tricholoma
      equestre were described. They had eaten 100-300 grams of this wild mushroom
      during nine consecutive meals. About 48 hours after the last meal containing the
      mushroom they developed fatigue, muscle weakness and myalgia, loss of appetite,
      mild nausea, profuse sweating. Maximal serum creatine kinase activity was 18,150
      U/L in the mother and 48,136 U/L in the son. Maximal serum levels of aspartate
      aminotransferase and alanine aminotransferase were 802 U/L and 446 U/L,
      respectively, in the mother and 2002 U/L and 454 U/L, respectively, in the son.
      All routine biochemical tests were within normal range. No other causes of
      rhabdomyolysis such as parasitic, viral, immune diseases, trauma or exposure to
      medications were found. All the above mentioned symptoms and biochemical
      abnormalities disappeared within 23 days of hospitalization. Our observation
      confirms the results of Bedry and co-workers that Tricholoma equestre contains a
      toxin, which can cause rhabdomyolysis.

PMID- 12184018
TI  - [The influence of media propagation of euthanasia on suicide attempts among
      terminally ill patients].
AB  - During consecutive two weeks of the year 2000 in the Clinic of Toxicology of
      Gdansk Medical University we hospitalised because of suicide attempts three women
      suffering from cancer and one suffering from sclerosis multiplex. All of them as
      main cause for this desperate action mentioned the lack of sufficient pain
      control, but the direct inspiration was the local TV programme about euthanasia.
      According to the information in the TV programme the patients took orally
      morphine sulphate in the dosage from 300 to 1000 (615 approx.) mg. In all the
      four patients acute respiratory insufficiency occurred, one subject needed
      approximately 60 hours of respiratorotherapy. Psychiatric consultation revealed
      reactive depression syndrome in all the cases, requiring pharmacological
      treatment. After being discharged from the Clinic the patients were sent to Pain
      Control Dispensary.

PMID- 12184019
TI  - [Suicidal attempts with old (currently unused) drug].
AB  - Suicidal attempt with old (currently unused) drug is described. The suicidal
      attempts are usually performed with the use of contemporary pharmacotherapeutics.
      In the report a case of suicidal attempt with old drug Tardyl is presented.
      Tardyl (Glutethimid) was prescribed to the patient and has been stored for 20
      years. The patient was previously treated for depression and many suicidal
      attempts. In the course of intoxication: balance disturbances, psychomotor
      retardation, changes in consciousness with temporary excitation were observed.
      The concentration of glutethimid in the urine was 1.1 mg% and 0.5 mg% in the
      blood. Patient was treated according to the general rules of intensive care.
      After 4 days of therapy the patient improved and was transferred to psychiatric
      unit in Koscian.

PMID- 12184020
TI  - [Pancreatic cancer and mast cells].
AB  - The paper presents 69-year old patient with a relatively long-term survival and a
      large number of mast cells (MCs) in pancreatic cancer. The patient was operated
      in February 1986 because of symptoms of pyloric stenosis and gastrojejunostomy
      was performed according to Brown's method. The patient died in September 1987 due
      to disseminated neoplastic disease. The survival time after the diagnosis was 583
      days. Histopathologic examination during operation and postmortem revealed
      pancreatic scirrhous adenocarcinoma. MCs in sections were stained with toluidine
      blue. The number of MCs per 20 microscopic fields in each of five sections at a
      magnification 200 x was counted, and the average count was 35 per one microscopic
      field. In a control group of 20 patients with pancreatic adenocarcinoma and no
      treatment, the identical but retrospective examinations were carried out using
      formalin-fixed and paraffin-embedded tumor sections. The count of MCs was from 2
      to 12 (average 8) per one microscopic field and no correlation between the number
      of MCs and the survival time in individual patients (average 79 days) was found.

PMID- 12184021
TI  - Ethanol therapy for toxic alcohols poisoning: drawbacks and side-effects.

PMID- 12184022
TI  - [Thyroiditis in patients operated on for goiter].
AB  - The paper is aimed at evaluating the frequency of incidence and the thyroiditis
      type in patients operated on for goiter. In the years 1989-2000, 5149 patients
      were operated on because of different thyroid disorders. The clinical data of 66
      patients with thyroiditis, diagnosed in a post-operating histopathological
      examination, were subject to a retrospective analysis. There were 64 women and 2
      men, aged from 22 to 70, on an average 50.1 years old. There were determined the
      preoperative diagnosis, the thyroid function--basing upon the levels of TSH and
      thyroid hormones, the type of operation effected as well as post operative
      complications. Then, there was also measured the weight of the resected lobes.
      The prevalent indication for the surgery was non-toxic goiter; instead, toxic
      goiter was such an indication only in a few cases. In most patients, the thyroid
      function revealed euthyreosis. The following complications were observed:
      transient hypocalcemia [two patients], transient paralysis of recurrent laryngeal
      nerve on one side [one], and wound suppuration [one]. The following types of
      thyroiditis were found in histopatological examination: Hashimoto (59 patients),
      Riedl (3 patients), de Quervain (2 patients) and non-specific thyroiditis (2
      patients). CONCLUSIONS: 1. Thyroiditis is a rare case in patients operated on for
      goiter. 2. The most frequent pathological finding is Hasimoto disease.

PMID- 12184023
TI  - [Application of immunofluorescence techniques in diagnostics of subepidermal
      autoimmune bullous dermatoses].
AB  - In the diagnostics of subepidermal autoimmune diseases, the crucial role is
      played by immunopathological studies. Immunofluorescence techniques are
      extensively used in routine investigations. In our research work, the application
      of these methods enabled us to establish the following disorders: pemphigoid (27
      cases), EBA (2), LABD (5), pemphigoid gestationis (3) and dermatitis
      herpetiformis (31). The results were successively discussed while analysing the
      data on autoimmunological etiopathogenesis disease.

PMID- 12184024
TI  - [Beta-thromboglobulin concentration in chosen parasitic diseases].
AB  - Blood platelets are active elements in the body defense mechanisms, e.g. in
      antiparasitic immunology. A platelet stimulation may result from a direct contact
      with a parasite, increased IgG and/or IgE concentrations, the presence of
      complement, CRP or lymphokins. This study was aimed at establishing whether a
      parasitic infection could induce a platelet activation. The study involved 35
      patients (30 patients were infected with Giardia intestinalis and 5 patients with
      Echinococcus granulosus). Blood for analysis was collected twice--before
      treatment (A1) and after treatment (A2). The concentrations of beta
      thromboglobulin were assayed by means of the set of ASSERA-CHROM, according to
      the immuno-enzymatic method with labelled antibodies. The platelet count was
      determined with a haematologic analyser. Although platelets do not get into a
      direct contact with the parasite, an increase in the concentration of b
      thromboglobulin is observed, and it may indicate the involvement of platelets in
      the parasitic disease.

PMID- 12184025
TI  - [Extrinsic coagulation pathway in peritoneally dialyzed patients treated with
      erythropoietin].
AB  - In chronic renal failure, disturbances in hemostasis are predominantly due to the
      defective platelet function and platelet/vessel wall interactions.
      Erythropoietin, used in the treatment of renal anemia, affects hemostasis in
      dialyzed patients. The work was aimed at assessing the components of extrinsic
      coagulation pathway in patients on continuous ambulatory peritoneal dialysis
      (CAPD) in the course of erythropoietin therapy. The studies were performed on 11
      CAPD patients, administered with subcutaneous erythropoietin in a dose of 2000 U
      three times a week for a 3 months time. Hemoglobin, hematocrit and erythrocyte
      count increased significantly after 1 month of the treatment. Tissue factor,
      tissue factor pathway inhibitor (total, free and truncated), factor VII and X as
      well as thrombomodulin-marker of endothelial celi injury did not change
      significantly during 3 months of erythropoietin therapy when compared to the
      baseline values. Erythropoietin treatment in CAPD patients did not affect
      significantly extrinsic coagulation pathway and endothelial function.

PMID- 12184026
TI  - [Chlamydia pneumoniae infections--diagnostic methods].
AB  - Gram-negative bacteria Chlamydia pneumonia was found in 1989 to cause acute and
      chronic respiratory tract infections. This agent has been as well associated with
      other disease: atherogenesis and coronary heart disease. This study is aimed both
      at making an introduction to the issues related to C. pneumoniae diagnosis and
      presenting contemporary laboratory methods. Given the limitations of traditional
      diagnostics methods, serodiagnosis (EIA) and nucleic acids amplification (PCR,
      hybridisation) provide the most convincing evidence of C. pneumoniae infections.
      Culture and direct fluorescence antibody (DFA) may be useful in confirming these
      results. A variety of methods applied can provide an opportunity to detect
      bacteria in different clinical samples--incl. sputum, nasopharyngeal and throat
      swabs, bronchoalveolar lavage (BAL) and tissues from biopsy and autopsy.

PMID- 12184027
TI  - [Atherosclerosis: a chronic inflammatory diseases].
AB  - In spite of years of intense investigations, the pathogenesis of atherosclerosis
      awaits final elucidation and its complications continue to challenge contemporary
      medicine. It is generally believed that atherosclerosis is the result of chronic
      and evolving fibroproliferative inflammatory response against harmful factors
      acting on the vascular wall. This work is a concise review of mechanisms
      participating in the initiation, evolution and complications of atherosclerosis.
      Endothelial cell dysfunction is discussed with emphasis on the role of
      endothelial adhesion molecules. Attention is focused on the function of
      monocytes/macrophages and lymphocytes as mediators of inflammation and immune
      response.

PMID- 12184028
TI  - [Dual role of nitric oxide in the pathogenesis of diabetic nephropathy].
AB  - Nitric oxide (NO) is a key mediator in renal physiology and pathology. In
      diabetic nephropathy, NO may exert destructive effects (hyperfiltration,
      peroxynitrate-mediated tissue injury) as well as exhibit certain protective
      properties (reduced TGF-beta expression and extracellular matrix expansion,
      inhibition of platelet aggregation). Here, we briefly review the biochemistry and
      pathophysiology of NO, and discuss the mechanisms underlying the contrasting
      effects of NO in diabetic nephropathy.

PMID- 12184029
TI  - [Hypoglycemia--a new view on the problem of classification and clinical
      diagnostic].
AB  - The commonly applied division of hypoglycemia into reactive and non-reactive one
      is too general and often times insufficient in clinical practice. The authors of
      this study presented a classification based on the clinical profile of patients
      with hypoglycemia. They also recommended patterns allowing proper diagnostic
      procedure in each classified group.

PMID- 12184030
TI  - [Irbesartan--antihypertensive treatment in patients with heart failure and
      diabetes mellitus].
AB  - Irbesartan (SR 47436; BMS-186295) is a selective non-peptide antagonist of
      angiotensin II type 1 receptor (AT1). Irbesartan inhibits the action of
      angiotensin II, which acts through the binding to the AT1 receptor. Many
      experimental and clinical data show that activation of AT1 receptors plays the
      crucial role in the development of hypertension, hypertrophy of left ventricle,
      progression of lipid disorders and impairment of renal function. Therefore, the
      pharmacological intervention with angiotensin II type 1 receptor antagonists
      could be used as a new therapeutic option in treatment of hypertension and its
      complications. The advantage of irbesartan is its long lasting blood pressure
      lowering action and the possibility of taking it once a day. The principle of its
      action is not only limited to blocking the AT1 receptor, but it also participates
      in many other reactions of the renin-angiotensin-aldosterone system. According to
      the reports published, irbesartan and other antagonists of angiotensin II type 1
      receptor seem to be a promising complement in the treatment of idiopathic
      hypertension, especially in patients with heart failure, diabetes and impaired
      renal function. Several studies showed that in addition to its long blood
      pressure lowering action (study of Pool, Fogari, Stumlple, Minran)--(possibility
      of taking the drug once a day), the AT1 antagonists reduced proteinuria (Sica et
      al.) without decreasing the creatinine clearance, improved the function of
      endothelium and inhibited the mitogen and proliferative action of angiotensin II
      on cardio-vascular system (Kahan et al., Tonkon et al., SILVER and ELITE trail).

PMID- 12184031
TI  - [Determinants of the age at natural menopause].
AB  - The age at natural menopause (ANM) varies due to environmental and genetic
      factors. Smoking accelerates ANM by about 1.5-2 years. Other factors which
      accelerate ANM are: nulliparity, short-length menstrual cycles and unilateral
      oophorectomy. In contrast, factors such as irregular menstrual cycles, height
      socioeconomic status, parity and giving birth before the age 25 all delay ANM.
      Nutritional factors also affect ANM. For example, vegetarian diet accelerates ANM
      by about 2 years; a high intake of fat, cholesterol, coffee also accelerate
      menopause, while moderate alcohol consumption delays it. However, the influence
      of dietary factors has not been adequately documented due to a relatively small
      number of studies. Moreover, genetic factors seem to influence ANM: for example,
      early menopausal age of the mother correlates with early menopausal age of her
      daughter. Factors such as the age at menarche, spontaneous abortions, passive
      smoking, weight and height, breast feeding, using of oral contraceptives,
      employment and depression, have all been suggested to influence menopausal age,
      but their impact needs to be established. Therefore, there is a need for
      longterm, follow-up studies which would allow to evaluate the impact of life
      style factors, including dietary factors on ANM. The knowledge of factors
      influencing ANM is crucial for medical practice, public health and reproductive
      biology. Menopause is the period during which serious health problems such as
      cardiovascular diseases and osteoporosis occur with increasing frequency. Knowing
      the factors which determine menopausal age may lead to lifestyle changes (such as
      not smoking), which would result in delaying menopause, and therefore prolonging
      natural estrogen protection.

PMID- 12184032
TI  - [Topical corticosteroids in dermatology--advantages and side effects].
AB  - In the article, the authors have presented the crucial stages of scientific
      research concerning topical steroids which contribute to reduce undesirable side
      effects and to improve the therapeutic index. Attention has been paid to the
      variety of factors which influence the absorption of steroids by the skin (kinds
      of drugs, their forms, types of dressing, regions of the skin, time of
      application). The mechanism of antiinflammatory, antipruritic and
      antiproliferation actions of steroids, conditioning their topical therapeutic
      effect, has been given. A four- and seven-graded classification, which takes into
      consideration the force of action of the topical steroids and is helpful in the
      daily medical practice, has been mentioned. There have been also listed most
      common systemic complications and especially the effects of chronic topical
      application of steroids on the skin.

PMID- 12184034
TI  - [Antimalarials in lupus erythematosus treatment].
AB  - Antimalarial therapy is regarded as the most successful treatment for cutaneous
      and also some symptoms of systemic lupus erythematosus. Although these drugs have
      been known for decades, the precise mechanisms of their action is not completely
      defined. Continuous research provides insight into the pathogenic mechanism of
      the antimalarial responsive disorders and facilitates the development of better
      targeted therapies. There are presented some relevant, putative and possible
      mechanisms by which antimalarials provide benefit in lupus patients.

PMID- 12184033
TI  - [Contemporary, noninvasive methods of wrinkles treatment, possibilities and
      esthetic dermatology].
AB  - Wrinkles are the most visible sign of the aging skin. The author presented
      characteristic changes in the epithelium and dermis for that type of skin and
      therapeutic possibilities utilised in the esthetic dermatology. They also
      undertook an attempt to classify patients for particular types of revitalization
      interventions (implants, botulin toxin, peelings).

PMID- 12184035
TI  - [Drug eruptions].
AB  - In the following paper, there have been discussed the mechanisms of reactions
      which may result from adverse drug effects. In particular, the paper shows a
      clinical picture of skin lesions and various dermatological entities in which
      drugs are triggering factors.

PMID- 12184036
TI  - Left ventricular true aneurysm without coronary artery occlusion--a case study.
AB  - BACKGROUND: Left ventricular true aneurysm is described as distinct area of the
      left ventricular wall with systolic dyskinesia where typical myocardial structure
      is replaced with fibrous tissue. Transmural infarction following occlusion of
      left anterior descending coronary artery is the most common cause of formation of
      the left ventricular aneurysm. CASE REPORT: A 51-year old white male, with the
      history of inferolateral wall myocardial infarction 6 years ago was admitted to
      the emergency department at the local hospital last year because of sudden
      cardiac arrest due to ventricular fibrillation in the course of inferolateral
      myocardial infarction. Later on the patient did not come back to work, felt very
      weak and had dyspnea on mild exertion. Coronary angiogram performed one year
      later (the patient refused coronary angiography examination at the time of
      myocardial infarction) showed normal coronary arteries with a recessive right
      coronary artery. The left coronary artery was wide with normal contrast flow.
      Ventriculography showed large, true dyskinetic aneurysm with mural thrombus in
      the apical segment of the left ventricular wall. Left ventricular ejection
      fraction was 30%. Patient was qualified for the aneurysmectomy. A large
      dyskinetic aneurysm (8 cm) of the apical and anterolateral segment of the left
      ventricular wall was detected intraoperatively. A fresh thrombus weighing 9 g was
      evacuated from the inside of the aneurysm. Stoney's aneurysmectomy was performed.
      Histopathology showed a typical picture of scar tissue without signs of active
      inflammation. CONCLUSION: Normal coronary angiogram does not exclude development
      of large true aneurysm of left ventricular wall of typical localization for acute
      occlusion of left anterior descendent artery.

PMID- 12184037
TI  - [Diagnostic difficulties in scanty symptomatic pituitary tumor].
AB  - Adenomas are the most frequent pituitary tumours and constitute up to 8% of
      intracranial tumors. They are divided according to size into microadenomas and
      macroadenomas, the latter are expanding suprasellary, and also infiltrate the
      base of the skull. Depending on histological staining, they are divided into
      neutrophilic, acidophilic and basophilic adenomas. Hormonally active adenomas are
      responsible for Cushing, Forbes and Albright diseases and acromegaly.
      Macroadenomas are responsible for chronic hypothalamo-pituitary axis
      insufficiency. Clinically, pituitary tumours produce local (headaches and vision
      deficiency) and general signs like hormonal disturbances. Diagnosis, localisation
      and size of pituitary tumours is made using radiological techniques. Treatment
      may consist of surgical (removing of the tumour and chiasma opticum
      decompression), pharmaco and radiotherapy. The case described illustrates the
      diagnosis of an oligosymptomatic pituitary tumour.

PMID- 12184038
TI  - [Development of diagnostic methods in upper gastrointestinal tract bleeding].
AB  - Since the first description of upper gastrointestinal bleeding, presented as
      ground coffee vomiting and melena by Galen Claudius in 200 A.D., we have been
      observing dynamic progress in the diagnostics of this disease. This article
      presents modern methods and diagnostic examinations used to detect and localise
      the bleeding source.

PMID- 12184039
TI  - Ovarian cancer screening and prevention.
AB  - OBJECTIVES: To review current ovarian cancer prevention and detection
      recommendations using a risk assessment framework, and discuss the genes related
      to hereditary ovarian cancer syndromes. DATA SOURCES: Published articles,
      consensus opinions, and reports. CONCLUSIONS: Women at highest risk are those
      with a family history and/or genetic predisposition. Management guidelines
      include pelvic exam, CA125, and transvaginal ultrasound, although their efficacy
      is limited. Individualized risk assessment can be useful in assisting women who
      face decisions regarding prevention options. IMPLICATIONS FOR NURSING PRACTICE:
      Nurses are challenged to identify women at increased risk for ovarian cancer, and
      to recognize the complex issues faced when these women pursue screening and
      prevention strategies.

PMID- 12184040
TI  - Ovarian cancer.
AB  - OBJECTIVES: To review the progress in the management of ovarian cancer in the
      last decade and future directions. DATA SOURCES: Research studies, review
      articles, and abstracts. CONCLUSIONS: There is an increased understanding of
      ovarian cancer biology, the genetic basis for hereditary ovarian cancer, staging
      and the role of cytoreductive surgery, and more effective chemotherapy, resulting
      in an increase in the percentage of patients who will live 5 years from the time
      of diagnosis. IMPLICATIONS FOR NURSING PRACTICE: The nurse can play an invaluable
      role as the options of treatment are considered and weighed against quality-of
      life considerations.

PMID- 12184042
TI  - Cancer of the cervix.
AB  - OBJECTIVES: To review the advances in the diagnosis, evaluation, staging, and
      treatment of cervical cancer that have been made in the past 10 years, and
      identify the work that still needs to be done. DATA SOURCES: Journal and review
      articles, book chapters, and research studies. CONCLUSIONS: Although cervical
      cancer has a preinvasive component and should be easily preventable, it has not
      been eradicated. Issues that prevent access to health care need to be addressed.
      IMPLICATIONS FOR NURSING PRACTICE: Nurses now have a more extended role in
      screening patients and educating them regarding the importance of preventive
      care. As new treatments are developed, the nurse is the one who will monitor the
      patient for side effects and assist with minimizing them. When all treatments
      fail in advanced disease, the nurse will assist the patient to deal with end-of
      life issues and symptom control.

PMID- 12184043
TI  - Endometrial cancer.
AB  - OBJECTIVES: To provide an update for nurses involved in the care of women at risk
      or being treated for endometrial cancer. DATA SOURCES: Review articles, research
      reports, and medical and nursing text-books. CONCLUSIONS: Endometrial cancer is
      the most common gynecologic malignancy. Although most women with endometrial
      cancer present with early stage disease and have an excellent chance of cure,
      approximately 6,600 women in the United States are expected to die from the
      disease in 2002. Treatment of patients with advanced or recurrent disease remains
      challenging, with no proven best standard of treatment. IMPLICATIONS FOR NURSING
      PRACTICE: Nursing plays an important role in prevention and early detection of
      endometrial cancer, patient education, patient care, and rehabilitation.

PMID- 12184041
TI  - Preinvasive diseases of the cervix, vulva, and vagina.
AB  - OBJECTIVES: To discuss the epidemiology, treatment, and psychosocial implications
      of preinvasive disease of the lower genital tract. DATA SOURCES: Review articles,
      research studies, and government publications. CONCLUSIONS: Routine cervical
      cytology has been one of the most successful public health screening programs
      accomplished over the last 50 years. However, our success has plateaued. The
      focus now is to address existing barriers to screening and treatment, and to
      develop an effective triage protocol for the management of abnormal cervical
      cytology. IMPLICATIONS FOR NURSING CARE: Nurses as patient advocates are best
      prepared to meet the culturally sensitive, financially, and geographical
      challenges of addressing barriers to screening and treatment.

PMID- 12184044
TI  - Less common gynecologic malignancies.
AB  - OBJECTIVES: To review the incidence, etiology, diagnosis, treatment, and nursing
      implications of the uncommon gynecologic malignancies of vulvar carcinoma,
      vaginal carcinoma, sex cord-stromal tumors of the ovary, and gestational
      trophoblastic tumors. DATA SOURCES: Research studies, review articles, medical
      and nursing textbooks. CONCLUSIONS: Vulvar and vaginal cancers, sex cord-stromal
      tumors of the ovary, and gestational trophoblastic tumors are rare malignancies
      constituting less than 5% of all malignant diagnoses. If detected early these
      malignancies have a high possibility of cure. IMPLICATIONS FOR NURSING PRACTICE:
      Nurses play an important role in the education of women and patients to the signs
      and symptoms of gynecologic malignancies, the disease process, treatment options,
      follow-up care, and resources available to these women.

PMID- 12184045
TI  - Symptoms affecting quality of life in women with gynecologic cancer.
AB  - OBJECTIVES: To review quality-of-life issues in women diagnosed with gynecologic
      cancers. DATA SOURCES: Research studies, review articles, and medical and nursing
      text-books. CONCLUSIONS: Women diagnosed with gynecologic cancers carry a heavy
      physical and emotional burden because of surgical morbidity, chemotherapy
      toxicities, loss of fertility, changes in body image, sexual concerns, and
      altered relationships. IMPLICATIONS FOR NURSING PRACTICE: Health care providers
      play a key role in the identification and treatment of the complications of
      cancer therapy. Minimizing the effect of the symptoms of gynecologic cancer may
      positively impact the patient's quality of life.

PMID- 12184046
TI  - The advocacy movement in gynecologic oncology.
AB  - OBJECTIVES: To review the development of the advocacy movement in gynecologic
      oncology. DATA SOURCES: Professional journals, texts, newspapers, organization
      newsletters and briefs, and internet web sites. CONCLUSIONS: Advocacy in
      gynecology oncology has grown tremendously in the past 5 years. Advocacy groups
      offer information and resources to patients and family members; other groups
      target public policy and federal funding. IMPLICATIONS FOR NURSING PRACTICE:
      Nursing must remain involved in all aspects of patient advocacy and partner with
      leading advocacy movements to effect health care change.

PMID- 12184047
TI  - Management of tumor lysis syndrome: prevention and treatment.
AB  - OBJECTIVES: To provide a review of the preventive and treatment strategies for
      tumor lysis syndrome (TLS). DATA SOURCES: Primary and tertiary literature and
      clinical experience. CONCLUSIONS: The oncology nurse can optimize outcomes in the
      patient at risk for TLS through a variety of prevention and treatment
      interventions: (1) aggressive patient monitoring for early identification and
      treatment; (2) minimize risk factors via thorough medication and nutritional
      histories, and assurance of proper prophylactic regimens; (3) assessment of
      optimal routes of drug delivery to assure medication bioavailability; and (4)
      reinforcement of the above with comprehensive patient education. IMPLICATIONS FOR
      NURSING PRACTICE: Awareness and effective use of prophylactic and treatment
      regimens related to TLS will positively impact patient outcomes. The oncology
      nurse is at the front line to identify issues related to effective management of
      TLS.

PMID- 12184048
TI  - Pediatric considerations in tumor lysis syndrome.
AB  - OBJECTIVES: To identify pediatric issues related to tumor lysis syndrome (TLS)
      focusing on potential differences in patient monitoring and management in the
      pediatric patient as opposed to the adult; to discuss family and caregiver
      education. DATA SOURCES: Primary and tertiary literature and clinical experience.
      CONCLUSIONS: Pediatric patients are at high risk for developing TLS given the
      high incidence of hematologic malignancies in this population. The goal of
      therapy is to implement preventive treatment regimens and, once evident, respond
      immediately to correct any electrolyte or metabolic abnormalities. Close
      monitoring for risk factors and immediate identification and intervention is
      essential in preventing the life-threatening consequences of TLS. IMPLICATIONS
      FOR NURSING PRACTICE: The pediatric oncology nurse can significantly impact
      clinical outcomes in patients with or at risk for TLS through vigilant monitoring
      and implementation of prevention and treatment strategies.

PMID- 12184049
TI  - Overview of tumor lysis syndrome.
AB  - OBJECTIVES: To provide a general overview of tumor lysis syndrome (TLS) focusing
      on the incidence, epidemiology, and patient outcomes associated with the
      syndrome; review the role of the oncology nurse in impacting patient outcomes and
      identify evolving issues relating to TLS. DATA SOURCES: Primary and tertiary
      literature related to TLS and clinical practice experience. CONCLUSIONS: Issues
      related to TLS continue to evolve and the oncology nurse plays a key role in
      patient management. As with other neoplastic disease-related complications (e.g.,
      pain, nausea/vomiting), knowledge of TLS and attention and intervention, where
      appropriate, can positively impact patient outcome. IMPLICATIONS FOR NURSING
      PRACTICE: The oncology nurse plays a critical role in impacting patient outcomes
      with respect to TLS ranging from collaboration with other disciplines to
      identifying patients at risk, through assessments, vigilant monitoring, and
      implementing optimal treatment regimens.

PMID- 12184050
TI  - Pathophysiology, signs, and symptoms of acute tumor lysis syndrome.
AB  - OBJECTIVES: To provide a review of the pathophysiology and corresponding signs
      and symptoms of tumor lysis syndrome (TLS); to review clinical and laboratory
      monitoring parameters. DATA SOURCES: Primary and tertiary literature and clinical
      experience. CONCLUSIONS: An understanding of the pathophysiology of TLS,
      meticulous assessment for signs and symptoms and monitoring of laboratory data,
      as well as early recognition of problems are essential for optimal patient
      outcomes. IMPLICATIONS FOR NURSING PRACTICE: Knowledge of the pathophysiology of
      TLS will assist the oncology nurse in better understanding the overall syndrome
      and allow improved patient care management through close clinical and laboratory
      monitoring of signs and symptoms, and, ideally, promote a proactive approach to
      managing TLS.

PMID- 12184051
TI  - Hypertension: a microvascular and tubulointerstitial disease.
AB  - The vast majority of patients with essential hypertension have structural changes
      in their kidneys consisting of preglomerular vascular disease
      ('arteriolosclerosis') and tubulointerstitial injury. Most authorities have
      assumed that these structural changes occur secondary to hypertensive renal
      injury. However, Goldblatt proposed that primary renal microvascular disease
      might be the cause of some forms of hypertension. In this paper we present recent
      studies from our group that support a role for both preglomerular vascular
      disease as well as the tubulointerstitial inflammatory response in mediating salt
      sensitivity. We propose that subtle acquired renal injury may underlie the
      etiology of some forms of salt-sensitive hypertension.

PMID- 12184052
TI  - Pathogenesis of lead-induced hypertension: role of oxidative stress.
AB  - Chronic exposure to low levels of lead causes hypertension in humans and
      experimental animals. Several mechanisms have been shown to contribute to the
      pathogenesis of lead-induced hypertension: (1) avid oxidation and inactivation of
      endogenous nitric oxide (NO) by reactive oxygen species leading to functional NO
      deficiency; (2) increased sympathetic activity and circulating noradrenaline
      coupled with decreased vascular and elevated renal beta-adrenergic receptor
      density; (3) increased angiotensin-converting enzyme (ACE) activity and elevated
      plasma renin, angiotensin II and aldosterone levels; (4) heightened kininase I
      and kininase II activities; (5) possible increase in endothelin and thromboxane
      production; and (6) lead-mediated inhibition of vascular smooth muscle Na(+)-K+
      ATPase leading to a rise in cellular Na+ and hence Ca2+ stores. This paper
      provides an overview of the epidemiology of lead-induced hypertension followed by
      a review of the available data on the above-mentioned topics.

PMID- 12184053
TI  - Restoration of glomerular haemodynamics and renal injury independent of arterial
      hypertension in rats with subtotal renal ablation.
AB  - To study whether prevention of renal injury using the anti-inflammatory drugs
      pentosan polysulphate (PPS) and mycophenolate mofetil (MMF) is associated with
      improvement of glomerular haemodynamics, PPS and MMF were compared with losartan.
      The awake systolic blood pressure (SBP), proteinuria (Uprot) and micropuncture
      studies were performed 30 days after five-sixths nephrectomy in untreated rats
      and in rats treated with PPS (100 mg/kg per day), MMF (30 mg/kg per day) or
      losartan (30 mg/kg per day). In the rats receiving no treatment, there was a rise
      in SBP (to 180-200 mmHg) and in Uprot, which were prevented by losartan. In the
      PPS and MMF groups, the SBP was elevated but the Uprot did not increase. In the
      untreated rats the total glomerular filtration rate (GFR) decreased (-80%) and
      the single-nephron GFR (37-42%), plasma flow (67-127%) and glomerular pressure
      (10-15 mmHg) increased. These changes were prevented by PPS and MMF to the same
      extent as by losartan: the rise in single-nephron GFR and plasma flow were
      reduced by 50% and the glomerular pressure was normal. In rats receiving
      losartan, this was due to the fall in arterial pressure, whereas in PPS- and MMF
      treated rats it was due to a rise in afferent resistance, indicating
      autoregulatory capacity. Total GFR was similar, despite the lower single-nephron
      GFR in treated groups, suggesting a larger proportion of functioning nephrons.
      Losartan, PPS and MMF significantly reduced glomerular sclerosis and tubular
      dilation and atrophy in association with a reduction in the lymphocyte and
      macrophage infiltrate. These results suggest an interaction between the
      haemodynamic and inflammatory changes that perpetuate each other during
      progression of renal injury. Renal protection provided by anti-inflammatory drugs
      is partially mediated by the prevention of glomerular haemodynamic alterations.

PMID- 12184054
TI  - Mechanisms of progressive renal disease: role of angiotensin II, cyclooxygenase
      products and nitric oxide.
AB  - There is mounting evidence that a number of inflammatory mechanisms play a
      crucial role in the pathogenesis of both immune- and non-immune-mediated
      glomerulopathies. These mechanisms include T lymphocyte activation, macrophage
      infiltration and the expression of several cytokines, growth factors and adhesion
      molecules. Inflammation may also be strongly influenced by three, until recently,
      unsuspected mediators: angiotensin II, cyclooxygenase derivatives and nitric
      oxide. Angiotensin II exerts several biological actions that are completely
      unrelated to its well-known haemodynamic effects, and can mediate cell
      proliferation, renal fibrosis and the synthesis of other proinflammatory
      compounds. Cyclooxygenase products have been long associated with non-renal
      inflammatory phenomena such as arthritis, and could mediate several steps of
      chronic renal inflammation. Although nitric oxide is generally regarded as a
      physiological vasodilator with irreplaceable homeostatic effects, it is possible
      that it participates in the pathogenesis of progressive nephropathies. Treatment
      with antagonists of these three compounds, alone or in combination, may represent
      a valuable therapeutic tool in the struggle to arrest or attenuate progressive
      renal disease.

PMID- 12184055
TI  - The renin-angiotensin system in progression, remission and regression of chronic
      nephropathies.
AB  - Chronic proteinuric nephropathies may progress to end-stage renal disease (ESRD)
      through a series of events relatively independent of the initial insult that
      causes parenchymal damage when the injury involves a critical number of nephrons.
      The key event is enhanced glomerular capillary pressure, which, among other
      effects, impairs glomerular permeability to proteins, which reach the lumen of
      the proximal tubule. In this pathological process angiotensin II has a central
      role. Reabsorption of filtered proteins contributes to the interstitial injury by
      activating intracellular events, including upregulation of vasoactive and
      inflammatory genes. Both interstitial inflammation and progression of disease can
      be limited by angiotensin-converting enzyme (ACE) inhibitors that strengthen the
      glomerular permeability barrier to proteins, thus limiting proteinuria and
      filtered protein-dependent inflammatory signals. Clinical evidence suggests that
      remission is now achievable in some patients with chronic nephropathies. The
      current lag time between starting treatment and remission, however, is such that
      a substantial proportion of patients still progress to ESRD before their renal
      function begins to stabilize. A multimodal approach aimed at reducing or
      abolishing all the risk factors for progression may shorten the time to remission
      for the majority of patients with proteinuric nephropathies.

PMID- 12184056
TI  - Dopaminergic receptors: a new antihypertensive mechanism.
AB  - The neutrotransmitter dopamine, precursor of noradrenaline, induces a variety of
      cardiovascular and renal physiological responses, including an increase in
      myocardial contractility and cardiac output without changes in heart rate,
      passive and active vasodilatation, diuresis and natriuresis. These responses
      result from its interaction with the dopamine receptors D1, D2, D3, D4 and D5. In
      addition, recent findings suggest the existence of D6 and D7 receptors. In some
      types of hypertension dopamine is known to influence the control of arterial
      pressure by influencing the central and peripheral nervous system and target
      organs such as the kidneys and adrenal glands. Since dopamine and its derivatives
      have been shown to have antihypertensive effects, it is important to review the
      physiological and pharmacological aspects of dopamine and its receptors, and the
      clinical uses that they could have in the therapy of arterial hypertension.

PMID- 12184057
TI  - The role of immune cells infiltrating the kidney in the pathogenesis of salt
      sensitive hypertension.
AB  - This work summarizes recent evidence that suggests that renal infiltration with
      immune cells plays a role in the pathogenesis of salt-sensitive hypertension. The
      presence of immunocompetent cells is a conspicuous finding in conditions
      associated with hypertension induced or maintained by a high salt intake. Studies
      in models of salt-sensitive hypertension following angiotensin II infusion and
      nitric oxide synthesis inhibition indicate that a reduction in the
      tubulointerstitial infiltration of lymphocytes and macrophages during the
      induction period results in protection from the subsequent development of salt
      sensitive hypertension. Reduction of the renal immune infiltrate in spontaneously
      hypertensive rats results in near normalization of the blood pressure. The
      reduction in the immune infiltrate is associated with a reduction in the number
      of cells expressing angiotensin II (some of which are immune cells) and a
      reduction in renal oxidative stress. Since increased intrarenal angiotensin
      activity tends to reduce filtered sodium and increase sodium reabsorption, and
      the tubulointerstitial damage resulting from oxidative stress can induce a shift
      to the right in the pressure-natriuresis relationship, these findings suggest
      potential mechanisms by which the immune infiltrate could induce or worsen salt
      driven hypertension.

PMID- 12184058
TI  - AT1 blockers: are there alternative pathways reducing cardiovascular risk?
      Introduction.

PMID- 12184059
TI  - Differentiation in the effects of the angiotensin II receptor blocker class on
      autonomic function.
AB  - Measurement of regional sympathetic activity with nerve recording and
      noradrenaline spillover isotope dilution techniques demonstrates activation of
      the sympathetic nerves of the heart, kidneys and skeletal muscle vasculature in
      younger patients with essential hypertension. Sympathetic overactivity in the
      renal sympathetic outflow is a prominent pathophysiological feature in obesity
      related hypertensives of any age. This increase in sympathetic activity is
      thought to both initiate and sustain the blood pressure elevation, and, in
      addition, contributes to adverse cardiovascular events. Sympathetic overactivity
      seems to particularly influence systolic pressure, by increasing the rate of left
      ventricular ejection, by reducing arterial compliance through increasing neural
      arterial tone, and via arteriolar vasoconstriction, by promoting rebound of the
      reflected arterial wave from the periphery. Inhibition of the renin-angiotensin
      system in certain circumstances appears to be able to reduce sympathetic nervous
      activity. Claims have been made for such an action at virtually every site in the
      sympathetic neuraxis. In reality, renin-angiotensin actions on the sympathetic
      nervous system are probably much more circumscribed than this, with the case
      perhaps being strongest for a presynaptic action of angiotensin on sympathetic
      nerves, to augment noradrenaline release. The ability of angiotensin receptor
      blockers to antagonize neural presynaptic angiotensin AT1 receptors appears to
      differ markedly between the individual agents in this drug class. In experimental
      models, such as the pithed rat, neural presynaptic actions are particularly
      evident with eprosartan. In a blinded study of crossover design, the effects of
      eprosartan and losartan on sympathetic nerve firing, measured by
      microneurography, and whole body noradrenaline spillover to plasma is currently
      being measured in patients with essential hypertension. A reduction in
      noradrenaline spillover disproportionate to any possible fall in nerve firing
      would document the presence of presynaptic antagonism of noradrenaline release.

PMID- 12184061
TI  - Sympatho-inhibitory properties of various AT1 receptor antagonists.
AB  - It is well known that angiotensin II (Ang II) can facilitate the effects of
      sympathetic neurotransmission. In the present study, using various experimental
      models, we investigated the inhibitory effects of several Ang II subtype 1
      receptor (AT1) antagonists on this Ang II-induced facilitation. We compared the
      sympatho-inhibitory potencies of the AT1 blockers with their respective potencies
      regarding inhibition of the direct vasoconstrictor effects of Ang II. In the
      isolated mesenteric artery, we investigated the effects of Ang II in the presence
      and absence of losartan, irbesartan and telmisartan on stimulation-induced
      vasoconstrictor responses. In the pithed rat, we studied the effect of AT1
      blockade on the sequelae of electrical stimulation of the thoracolumbar
      sympathetic outflow (presynaptic AT1 blockade) as well as on dose-response curves
      elicited by exogenous Ang II (postsynaptic AT1 blockade). Additionally, we
      compared the sympatho-inhibitory of irbesartan in spontaneously hypertensive
      (SHR) and Wistar-Kyoto (WKY) rats. In the isolated mesenteric artery, Ang II (10
      nM) significantly enhanced stimulation-induced vasoconstrictor responses. The
      enhancement could be antagonized in a concentration-dependent manner by losartan
      (1 nmol/l to 1 mumol/l), irbesartan (0.1 nmol/l to 0.1 mumol/l) and telmisartan
      (0.01 nmol/l to 0.01 mumol/l). The sympatho-inhibitory potency was telmisartan >
      irbesartan > losartan. In the pithed normotensive rat, the stimulation-induced
      increase in diastolic blood pressure (DBP) as well as the Ang II-elicited DBP
      response were dose-dependently reduced by all the AT1 receptor blockers
      investigated. The order of potency with respect to sympatho-inhibition was
      eprosartan > valsartan = candesartan = embusartan = telmisartan > losartan >
      irbesartan (comparison of doses which at 2 Hz reduced delta DBP by 20 mmHg,
      differences significant at P < 0.05). The order of potency regarding inhibition
      of the Ang II-induced DBP increase was candesartan > embusartan = valsartan =
      eprosartan = telmisartan > irbesartan > losartan (comparison of the antagonist
      concentration, in the presence of which twice the agonist concentration, in the
      presence of which twice the agonist concentration is needed to cause the same
      effect [pA2 values], differences significant at P < 0.05). In the pithed SHR and
      the normotensive WKY rat the sympatho-inhibitory potency of irbesartan did not
      differ significantly between both strains. It can be concluded that all AT1
      receptor antagonists appear to possess sympatho-inhibitory properties, which may
      be of potential interest in the treatment of hypertension and heart failure. Our
      findings suggest differences in pre- and postsynaptic inhibition between the
      various compounds, since for eprosartan and losartan the sympatholytic doses and
      postsynaptic inhibitory doses differed far less than for the other AT1 receptor
      antagonists.

PMID- 12184060
TI  - AT1 blockers and uric acid metabolism: are there relevant differences?
AB  - BACKGROUND: Serum urate is commonly elevated in essential hypertension (26-33%).
      Some studies have claimed that losartan increases urinary uric acid excretion and
      diminishes serum urate levels. However, a detailed, controlled study on the
      influence of losartan on uric acid metabolism in hypertensive patients has not
      been performed and the existent results are conflicting. Two small studies
      claimed that losartan reduced serum urate levels but only one showed a
      simultaneous increased uric acid excretion rate. The development of several AT1
      receptor blockers raises the question whether these antihypertensive drugs
      influence uric acid metabolism. STUDY: In a randomized, prospective (4 weeks),
      double blind, parallel study we have compared the influence of losartan (50
      mg/day) versus eprosartan (600 mg/day) on uric acid metabolism in 58 patients
      with mild to moderate essential hypertension. The mean uric acid to creatinine
      ratio change from baseline at 4 weeks was +0.11 for losartan and -0.04 for
      eprosartan (P < 0.01). The mean increase in 24-h urinary uric acid excretion with
      losartan was +0.7 mmol/24 h (25% increase from baseline). The change in serum
      urate levels versus baseline was similar after 4 weeks with losartan (-23.4
      mumol/l) and eprosartan (-19.5 mumol/l). Patients with hyperuricemia in both
      treatment groups showed similar modifications of uric acid metabolism compared
      with non-hyperuricemic subjects. Blood pressure control was achieved in 22
      patients (73%) with eprosartan and in 16 (53%) with losartan. CONCLUSIONS:
      Losartan increased uric acid excretion in hypertensive patients but eprosartan
      did not. Neither AT1 receptor antagonist substantially modified serum urate
      concentrations.

PMID- 12184062
TI  - The clinical profile of the angiotensin II receptor blocker eprosartan.
AB  - Angiotensin II receptor antagonists block angiotensin II type 1 (AT1) receptors
      and reduce the pressor effects of angiotensin in the vasculature. By this
      mechanism, they induce similar pharmacological effects to angiotensin-converting
      enzyme (ACE) inhibitors, resulting in a lowering of blood pressure (BP). However,
      AT1 antagonists differ from ACE inhibitors with respect to side effects, and
      induce less cough, which is related to bradykinin activation. Within the class of
      angiotensin II antagonists, eprosartan differs from other currently clinically
      available agents in terms of its chemical structure and its dual pharmacological
      mode of action. Eprosartan acts not only at vascular AT1 receptors but also at
      presynaptic AT1 receptors, causing inhibition of sympathetically stimulated
      noradrenaline release. Eprosartan is not metabolized by cytochrome P450 enzymes
      and therefore has a low potential for metabolic drug interactions, which may be
      of importance when treating the elderly and patients on multiple drugs. In
      clinical trials eprosartan has proven to be at least as effective as the ACE
      inhibitor enalapril in reducing BP, but with a significantly lower incidence of
      side effects. Eprosartan is safe, effective and well tolerated in long-term
      treatment, either as monotherapy or in combination with other antihypertensive
      drugs such as hydrochlorothiazide.

PMID- 12184063
TI  - [Analysis of quantitative trait loci (QTLs) of multifactorial diseases by using
      animal models: basic theory and methods used for the analysis].

PMID- 12184064
TI  - [Function and medical significance of a growth factor, midkine].

PMID- 12184065
TI  - [Recognition of methylated DNA].

PMID- 12184067
TI  - [An NMR method for the determination of the interface of large protein-protein
      complexes].

PMID- 12184066
TI  - [Molecular mechanisms for bleomycin resistance].

PMID- 12184068
TI  - [Structural medicine and structure-based drug design for prion diseases].

PMID- 12184069
TI  - [A finding of isoleucine derivative in recombinant protein].

PMID- 12184070
TI  - [Eukaryotic mRNA 5'-capping enzyme: its divergent structure and interaction with
      RNA polymerase II transcription complex].

PMID- 12184071
TI  - [Frederick Sanger, the pioneer of the sequence determination of protein and
      nucleic acids].

PMID- 12184072
TI  - [How to use MolScript?].

PMID- 12184073
TI  - [Tell me about algorithms in bioinformatics, Dr. Ochanomizu].

PMID- 12184074
TI  - [Management of chemicals in laboratories: principle and legislations].

PMID- 12184075
TI  - [Status of life science research at Northwestern University--Studies on gene
      expression of beta-globin].

PMID- 12184076
TI  - Pressure-release versus rigid reflector for extracorporeal shockwave lithotripsy.
AB  - PURPOSE: To evaluate the advantages and disadvantages of using a pressure-release
      reflector instead of a rigid reflector to concentrate shockwaves for
      extracorporeal shockwave lithotripsy (SWL). MATERIALS AND METHODS: As in all
      electrohydraulic lithotripters, shockwaves were generated by electrical breakdown
      of water between two electrodes, located at the focus (F1) closest to a
      paraellipsoidal reflector. A pressure-release reflector, made out of polyurethane
      foam, was constructed and tested on a research lithotripter using kidney stone
      models. Fragmentation data and pressure measurements were compared with those of
      a conventional rigid reflector tested on the same device. RESULTS: The weight of
      stone model fragments remaining after shockwave exposure was less with the
      pressure-release reflector after screening through a 3.0 x 3.0-mm mesh. The
      residual fragment weight was less with the rigid reflector using 1.0 x 1.0- and
      0.6 x 0.6-mm meshes. CONCLUSION: Pressure-release reflectors may maintain
      acceptable stone fragmentation while offering improved patient safety and should
      be considered for SWL.

PMID- 12184077
TI  - Current management of urolithiasis: progress or regress?
AB  - PURPOSE: To assess the impact of the development of less powerful second- and
      third-generation shockwave lithotripters on surgical stone therapy in light of
      recent advances in ureteroscopy and laser lithotripsy. As such, we sought to
      identify current trends in the treatment of stone disease, both at our university
      medical center and nationally, and to contrast them with the corresponding data
      from 1990. PATIENTS AND METHODS: All urolithiasis procedures (ureteroscopy, SWL,
      open surgery, and percutaneous stone removal) performed in 1998 were compared
      with all urolithiasis procedures performed 8 years earlier (1990) at a single
      institution (Washington University, St. Louis). In addition, Medicare data for
      each year from 1988 through 2000 were collected from the Health Care Financing
      Administration to assess the national trends for open stone surgery,
      ureteroscopic stone removal, SWL, and percutaneous nephrolithotomy. RESULTS: At
      Washington University, the number of percutaneous stone removals remained stable;
      however, the overall number of ureteroscopies increased by 53%, while the number
      of SWLs, decreased by 15%. The Medicare data likewise reflect a marked decrease
      in open stone surgery and a marked increase in ureteroscopic stone surgery with a
      slight increase in SWL. Utilization of percutaneous nephrolithotomy remained
      unchanged. CONCLUSIONS: We believe this trend toward ureteroscopy is attributable
      to several factors: improved, smaller rigid and flexible ureteroscopes; the
      availability of more effective intracorporeal lithotripters (e.g., pneumatic and
      holmium laser), and the lack of development of lower cost, more effective SWL.
      This is an unfortunate trend, as we are moving away from the noninvasive
      treatment that was the hallmark of urolithiasis therapy at the beginning of the
      last decade toward more invasive endoscopic therapy. Increased research efforts
      in SWL technology are sorely needed.

PMID- 12184078
TI  - Clinical use of the holmium: YAG laser in laparoscopic partial nephrectomy.
AB  - PURPOSE: To report on the technique and utility of the holmium: YAG laser in
      performing laparoscopic partial nephrectomy (LPN). PATIENTS AND METHODS: Three
      patients with indications for LPN (complex cyst, nonfunctioning lower pole, renal
      mass) underwent parenchymal-sparing procedures with the Ho:YAG laser. The kidney
      was identified using a transperitoneal laparoscopic technique. Gerota's fascia
      was opened, and the renal mass/nonfunctioning lower pole was resected using the
      laser. Settings of 0.2 J/pulse at 60 pulses/sec and 0.8 J/pulse at 40 pulses/sec
      were used. RESULTS: All three procedures were performed successfully with minimal
      blood loss and without the need for hilar occlusion. Although the laser alone was
      hemostatic, fibrin glue was applied in two cases and oxidized cellulose in one
      case to reinforce the tissue against delayed bleeding. There were no
      perioperative complications, and all patients left the hospital within 3 days.
      CONCLUSIONS: At high power settings, the Ho:YAG laser is an effective tool for
      LPN. It results in good hemostasis without the need for hilar occlusion. This
      technique promises to facilitate the laparoscopic management of renal tumors and
      nonfunctioning moieties of duplicated systems.

PMID- 12184079
TI  - Percutaneous hepatolithotomy: the Northwestern University experience.
AB  - Obstruction of intrahepatic ducts by calculi can lead to abdominal pain,
      cholestasis, abscesses, and cholangitis. Patients with stones recalcitrant to
      extraction using endoscopic retrograde cholangiopancreatography (ERCP) have
      traditionally been referred to a general surgeon for open stone extraction or
      hepatic lobectomy despite its great potential morbidity. Borrowing techniques,
      instrumentation, and experience in performing percutaneous nephrolithotomy, we
      describe our experience with percutaneous hepatolithotomy (PHL), a minimally
      invasive, safe, and effective alternative to open surgery for recalcitrant
      biliary stones.

PMID- 12184080
TI  - Bioabsorbable SR-PLGA horn stent after antegrade endopyelotomy: a case report.
AB  - PURPOSE: To evaluate the suitability of a bioabsorbable stent as a partial
      internal catheter after percutaneous endopyelotomy in ureteropelvic junction
      (UPJ) obstruction therapy. PATIENT AND METHODS: The material for the helical
      spiral stents was a copolymer of polylactide and glycolide (PLGA; L:G ratio
      80/20). The self-reinforcement (SR) was accomplished by heating and drawing by
      Bionx Implants Ltd, Tampere, Finland. The stents were horn shaped, with an
      initial outside diameter 6 to 3.0 mm +/- 0.2 mm and a length of 90 mm. The stent
      was partially degraded before insertion so it would degrade faster from the
      distal end, proceeding gradually to the proximal end. According to in vitro
      estimation, the degradation time of the material was 2 to 2.5 months. The
      railroaded cold-knife technique was used for antegrade endopyelotomy. After
      relief of the UPJ obstruction, the stent was pushed to the upper ureter. RESULTS:
      The 37-year-old male patient had under open pyeloplasty 5 years previously. He
      had a pelvic stone 32 mm in diameter and tight restenosis of the UPJ.
      Percutaneous lithotripsy, incision of the stenosis, and application of the SR
      PLGA helical horn-shaped spiral stent was without early or late complications.
      Eighteen months after the operation, retrograde pyelography showed the UPJ to be
      totally unobstructed. CONCLUSIONS: The bioabsorbable horn-shaped SR-PLGA helical
      spiral stent proved a suitable alternative for stenting of the UPJ after
      antegrade endopyelotomy, bringing a reduced need for postoperative percutaneous
      kidney drainage and no need for subsequent stent removal. The bioabsorbable
      helical stent works as a partial catheter, which prevents vesicoureteral reflux
      and reduces the risk of postoperative renal infection.

PMID- 12184081
TI  - Laparoscopic excision of suspected extra-adrenal pheochromocytoma located in the
      mesenteric root.
AB  - A 35-year-old woman presented with symptoms consistent with pheochromocytoma.
      Biochemical evaluation was equivocal. An MRI scan demonstrated an extra-adrenal
      high-intensity lesion on a T2-weighted sequence, which supported the suspicion of
      an extra-adrenal pheochromocytoma. Laparoscopically discovered to be located in
      the root of the small bowel mesentery, the 5-cm mass was excised along with a
      segment of small bowel. Pathology examination demonstrated fibromatosis, a benign
      lesion.

PMID- 12184082
TI  - Office-based cystoureteroscopy for assessment of the upper urinary tract.
AB  - Nephron-sparing management of malignant or benign lesions of the upper tracts
      creates the need for surveillance. This usually requires serial endoscopic
      assessment in the operating room under general anesthesia. Herein is presented a
      novel alternative to follow selected patients in the office setting using readily
      available adult cystoscopic equipment.

PMID- 12184083
TI  - Interstitial laser coagulation and biodegradable self-expandable, self-reinforced
      poly-L-lactic and poly-L-glycolic copolymer spiral stent in the treatment of
      benign prostatic enlargement.
AB  - BACKGROUND AND PURPOSE: Interstitial laser coagulation of the prostate (ILCP)
      induces necrosis, edema, and an increased risk of postoperative urinary
      retention. The object here was to evaluate the efficacy, safety, and utility of a
      new self-expandable self-reinforced (SR) PLGA copolymer(lactic:glycolic ratio
      80/20) spiral stent inserted after ILCP to promote voiding. The SR-PLGA stent has
      a degradation time of 2 to 2.5 months. PATIENTS AND METHODS: Fifty men with a
      mean age of 70.5 years (range 52-85 years), suffering from lower urinary tract
      symptoms secondary to benign prostatic enlargement underwent ILCP. A suprapubic
      catheter was inserted, ILCP performed, and an SR-PLGA 80/20 spiral stent inserted
      on completion of the operation. The suprapubic catheter was removed when voiding
      commenced. As prophylactic antibiotic, ciprofloxacin was used in a single dose
      before ILCP, followed by trimethoprim or nitrofurantoin for 2 weeks. RESULTS: All
      except three patients started to void on the first postoperative day. In two of
      the three cases, the stent had moved proximally and had to be relocated,
      whereafter voiding succeeded. The mean maximum and average flow rates increased,
      while DAN-PSS-1 symptom score and post voiding residual urine volume decreased
      statistically significantly. At 2 months, the stent was still intact in the
      urethra in all except three patients. At 4 months, it had been degraded into
      small fragments, and at 6 months, it had been completely eliminated. The only
      exceptions were three patients with an uncalcified piece of the stent in the
      bladder. Half of the patients had irritative symptoms caused at least partly by
      ILCP itself; 10% had asymptomatic urinary infection postoperatively. CONCLUSIONS:
      The self-expandable SR-PLGA copolymer stent is safe and highly biocompatible. It
      ensures voiding in the case of temporary obstruction caused by prostatic edema.
      The degradation time is long enough in all patients to cover the need for
      postprocedure urinary drainage.

PMID- 12184084
TI  - [What hopes do I have for the near future of medicine?].

PMID- 12184085
TI  - [Towards personal communication technology and health care].

PMID- 12184086
TI  - [Can medicine become more of a part of society?].

PMID- 12184087
TI  - [Future of medicine--thoughts and hopes].

PMID- 12184088
TI  - [From the language of natural sciences to multilingualism].

PMID- 12184089
TI  - [What does a historian expect from medicine?].

PMID- 12184090
TI  - [Hopes, fears and feelings].

PMID- 12184091
TI  - [Applications of genetic information will proceed, mental health problems will
      stay].

PMID- 12184092
TI  - [Health care and the economic way of thinking].

PMID- 12184093
TI  - [Self, Medicine and Sociology].

PMID- 12184094
TI  - [Physics as a helping science for Medicine].

PMID- 12184095
TI  - [Not longer, but better life].

PMID- 12184096
TI  - [Chronosophy and Medicine in the future].

PMID- 12184097
TI  - [The last, house and Eden of Medicine].

PMID- 12184098
TI  - [The importance of the childhood].

PMID- 12184099
TI  - [Outside of the hospitals].

PMID- 12184100
TI  - [Resources in the future].

PMID- 12184101
TI  - [Will the attitudes change?].

PMID- 12184102
TI  - [Life and health as basic rights].

PMID- 12184103
TI  - [On many fronts, together and separately].

PMID- 12184104
TI  - [Situation is under the control].

PMID- 12184105
TI  - [Positioning mobile phone communication and health care services].

PMID- 12184106
TI  - [Together for the children in the world].

PMID- 12184107
TI  - [To relieve and console and not to hurt].

PMID- 12184108
TI  - [Three kinds of knowledge].

PMID- 12184109
TI  - [Miracle makers and preventive work].

PMID- 12184110
TI  - [A musician taking a peep into the unused possibilities of medicine].

PMID- 12184111
TI  - [Ethical responsibility has to be taken].

PMID- 12184112
TI  - [From medicine to health science--a dream about the future].

PMID- 12184113
TI  - [Brain, genes and cosmetics].

PMID- 12184114
TI  - [Rites of the cure].

PMID- 12184115
TI  - [Medicine and ethics].

PMID- 12184116
TI  - [A hospital for the incurable people].

PMID- 12184117
TI  - [Polysaccharide for adults, a new conjugate vaccine for infants].

PMID- 12184118
TI  - [Cardiac effects of antidepressant agents].

PMID- 12184120
TI  - [Mesenteric venous thrombosis].

PMID- 12184119
TI  - [Septic syndromes treated in intensive care unit at Turku University Hospital
      1993-8].

PMID- 12184121
TI  - [When and how should polycystic ovary syndrome be treated?].

PMID- 12184122
TI  - [A persistent chest pain in a middle-aged woman].

PMID- 12184123
TI  - [Adolf von Becker: A mother's joy].

PMID- 12184124
TI  - [Why should the risk factors of coronary heart disease be considered already in
      early childhood?].

PMID- 12184125
TI  - [When and how should hyperlipidemias in children and adolescents be treated?].

PMID- 12184126
TI  - [Childhood obesity increases the risk of coronary artery disease].

PMID- 12184127
TI  - [Nutrition of Finnish children and possibilities to influence it via
      interventions].

PMID- 12184128
TI  - [Smoking in Finnish children and adolescents].

PMID- 12184129
TI  - [Blood pressure in children].

PMID- 12184130
TI  - [Exercise habits of Finnish children and adolescents as it is today].

PMID- 12184131
TI  - [Psychosocial risk factors of cardiovascular diseases in children].

PMID- 12184132
TI  - [What should be done already now?].

PMID- 12184133
TI  - Neuropathophysiology of irritable bowel syndrome.
AB  - Widespread symptoms associated with the irritable bowel syndrome (IBS) are
      abnormal defecation and abdominal pain, both of which can be exacerbated by
      psychogenic stress. Disordered defecation may present as diarrhea or
      constipation. A subgroup of IBS patients alternate from one to the other over
      time. Urgency to stool often accompanies the diarrheal-state, and patients with
      the constipation-predominant form of IBS report straining and the feeling of
      incomplete evacuation. Basic scientific research aims for improved understanding
      of the physiology and pathophysiology of the digestive systems from which the
      arrays of IBS symptoms emerge. The key systems for the defecation-related
      symptoms are the intestinal secretory glands, the musculature, and the nervous
      system that controls and integrates their activity. Abdominal pain and discomfort
      arising from these systems adds the dimension of sensory neurophysiology. This
      review details current concepts of the underlying pathophysiology in terms of the
      physiology of intestinal secretion, motility, nervous control, sensing function,
      immuno-neural communication, and the brain-gut axis.

PMID- 12184134
TI  - Evolving concepts in the pathophysiology of functional gastrointestinal disorder.
AB  - Functional gastrointestinal disorder (FGID) is common and may affect any part of
      the digestive tract from the esophagus to the rectum. Functional dyspepsia and
      the irritable bowel syndrome (IBS) are the most commonly recognized and until
      recently were considered distinct entities. In recent years, however, new
      observations and studies of the afferent nervous system have extended our
      concepts of both IBS and dyspepsia and suggest that these conditions may have
      common triggers and expression from similar pathophysiological processes.

PMID- 12184135
TI  - Brain research in functional gastrointestinal disorders.
AB  - The current understanding is that functional gastrointestinal disorders (FGIDs)
      result from dysregulation of the bidirectional communication between the gut and
      the brain (i.e., the brain-gut axis), modulated by various psychosocial and
      environmental factors (i.e., the biopsychosocial model). This concept has led to
      a growing interest in the research of brain function in relation to gut motor and
      sensory function. Brain research on the mechanisms that are involved in the
      generation of gastrointestinal symptoms includes studies of the gut response to
      brain stimulation with technique such as transcranial magnetic stimulation or
      studies of the brain response to gut stimulation by cortical evoked potentials,
      positron emission tomography, and functional magnetic resonance imaging. Studies
      using these techniques have shown that visceral/gut sensation involves activation
      of several brain regions that are associated with various brain functions,
      including sensation, cognition, and affect. The complexity of the brain response
      to visceral stimulation and the multidetermined nature of FGIDs make studies of
      brain function in FGID patients difficult and demands great caution in
      interpreting their results. Nevertheless, brain research in FGIDs is an emerging
      field and suggests that patients with irritable bowel syndrome differ from
      healthy subjects in the way that their brain response to visceral (e.g., rectal)
      distention. These studies emphasize the role of the central nervous system in
      conducting and processing visceral signals and suggest that alteration in brain
      processes involving perception and affective responses might be key factors in
      the pathogenesis of functional gastrointestinal symptoms.

PMID- 12184136
TI  - The nature of pain in irritable bowel syndrome.
AB  - The diagnosis of irritable bowel syndrome (IBS) is arbitrary, being based on
      criteria defined by consensus rather than specific biologic markers. IBS is
      merely a consortium of symptoms and as presently defined is no more a disease
      than dyspnea or fatigue are diseases. In this context, it is therefore not
      surprising that defining the nature of pain has proven elusive. It is often
      etiologically assumed that the origins of the pain seen in IBS patients are
      mechanistically distinct from those of some of the other symptoms of IBS such as
      diarrhea and constipation. In addition pain is assumed to be part of a continuum
      ranging from complete absence of any pain to varying degrees of discomfort to
      severe pain. Both of these assumptions should be challenged: there are no data to
      support the notion that discomfort and pain experienced in IBS are mediated
      through different pathways than symptoms such as bloating or that they are not
      merely the consequence of the physiological perturbations associated with altered
      bowel function. Similarly one can easily argue that visceral pain may actually be
      the cause rather than the effect of the altered gut function seen in IBS.
      Abdominal discomfort could then be the consequence of the latter and be only
      indirectly related to pain. It is likely that central (such as stress) and
      peripheral factors (such as intestinal infection) will produce similar symptoms
      but via markedly different pathways. It may be time to deconstruct IBS as a
      concept and to approach the clinical picture from a mechanistic rather than a
      phenomenological perspective, particularly if we are interested in understanding
      the basis of the symptoms and develop effective therapeutic modalities. Our
      patients deserve no less.

PMID- 12184137
TI  - Clinical assessment of irritable bowel syndrome.
AB  - Because irritable bowel syndrome (IBS) is a prevalent cause of visits to the
      gastroenterologist, it is extremely important to have accurate guidelines for the
      diagnosis. During the clinical assessment of IBS, the physician must look for the
      gastrointestinal symptoms, extraintestinal symptoms, and psychological history
      that are commonly associated with IBS. There are three diagnostic criteria that
      may be used in the IBS diagnosis: Manning, Rome I, and Rome II. Although there is
      discrepancy about which is most effective, we recommend that the Rome II be used
      in clinical practice. To confidently diagnose IBS, the physician must rule out
      organic disease as a cause of symptoms. This can be done by evaluating the
      patient's symptoms and screening for "red flags." The diagnostic strategy for IBS
      involves a thorough evaluation of the patient: taking a patient history,
      performing a physical exam, and performing the appropriate diagnostic tests when
      necessary.

PMID- 12184138
TI  - Irritable bowel syndrome: basis of clinical management strategies.
AB  - Patients with irritable bowel syndrome (IBS) are often described as challenging.
      The diagnosis of IBS can safely be made using the Rome II criteria in conjunction
      with a thorough physical examination and a limited number of diagnostic studies.
      Although the diagnosis is generally made with a high degree of accuracy, the
      pathophysiology of IBS remains elusive, and treatment can be frustrating for both
      patient and physician alike. Important areas of research focus on the psychology
      of IBS, visceral hypersensitivity, motility abnormalities (e.g., heightened
      gastrocolonic response), and the "brain-gut axis." A multidisciplinary effort is
      often required to ameliorate symptoms and improve the patients' quality of life.
      This review article will discuss the myriad of treatments available for patients
      with IBS, and provide both a clinical and practical discussion of their use,
      providing evidence where available and clinical experience where it is not.

PMID- 12184139
TI  - Diet in the irritable bowel syndrome.
AB  - Patients with irritable bowel syndrome (IBS) often request dietary
      recommendations. They must eat, and they want to know what to eat. Present
      national guidelines recommend dietary treatment with fiber for IBS patients with
      constipation. Diet recommendations are made based on symptoms. There may be
      different dietary recommendations for constipation, diarrhea, and pain or
      bloating. This article reviews the relationship of foods to IBS and issues of
      food intolerances and hypersensitivities, and recommendations for diet therapy.
      The role of dietary fiber, both soluble and insoluble, is reviewed. Although
      there are few studies to substantiate exact diets, broad dietary plans are
      recommended for the different symptoms of IBS. In addition, the recent literature
      on probiotics and prebiotics pertinent to IBS is reviewed.

PMID- 12184140
TI  - Psychotropic agents in irritable bowel syndrome.
AB  - The use of antidepressants to treat patients with irritable bowel syndrome (IBS)
      has been extended in recent years because of their possible neuromodulatory and
      analgesic effects, generally in doses that do not have antidepressant effects.
      There seems to be sufficient evidence to support the recommendation that
      psychotropic agents may be effective in two clinical scenarios that are not
      mutually exclusive. The first is in patients with IBS who have pain and related
      symptoms that are unresponsive to medical therapy. The second is in patients with
      IBS who have concomitant psychologic dysfunction. This article reviews the
      evidence to support these recommendations and guidelines, which may be used to
      optimize medical management in these patients.

PMID- 12184141
TI  - Irritable bowel syndrome neuropharmacology. A review of approved and
      investigational compounds.
AB  - Anticholinergics and prokinetics are mainstays of therapy for Irritable Bowel
      Syndrome (IBS) patients despite their limited efficacy and troublesome side
      effect profile. The clinical limitations of these drugs are a result of their
      relative broad and nonspecific pharmacologic interaction with various receptors.
      Recent advances in gut physiology have led to the identification of various
      receptor targets that may play a pivotal role in the pathogenesis of IBS.
      Medicinal chemists searching for safe and effective IBS therapies are now
      developing compounds targeting many of these specific receptors. The latest
      generation of anticholinergics, such as zamifenacin, darifenacin, and YM-905,
      provide selective antagonism of the muscarinic type-3 receptor. Tegaserod, a
      selective 5-HT4 partial agonist, tested in multiple clinical trials, is effective
      in reducing the symptoms of abdominal pain, bloating, and constipation.
      Ezlopitant and nepadudant, selective antagonists for neurokinin receptors type 1
      and type 2, respectively, show promise in reducing gut motility and pain.
      Loperamide, a mu (mu) opioid receptor agonist, is safe and effective for IBS
      patients with diarrhea (IBS-D) as the predominant bowel syndrome. Fedotozine, a
      kappa (kappa) opioid receptor agonist, has been tried as a visccral analgesic in
      various clinical trials with conflicting results. Alosetron, a 5-HT3 receptor
      antagonist, has demonstrated efficacy in IBS-D patients but incidents of ischemic
      colitis seen in post-marketing follow-up resulted its removal from the market.
      Compounds that target cholecystokinin. A, N-methyl-D-aspartate, alpha 2
      adrenergic, and corticotropin-releasing factor receptors are also examined in
      this review.

PMID- 12184142
TI  - Summation: irritable bowel and the irritable physician.

PMID- 12184143
TI  - Irritable bowel syndrome: classification and conceptualization.
AB  - The irritable bowel syndrome is one of a group of functional gastrointestinal
      disorders within the Rome classification system that is characterized by
      abdominal discomfort or pain associated with a change in stool habit. It is a
      multidetermined biopsychosocial disorder in which physiological, psychological,
      behavioral, and environmental factors may contribute to the clinical expression
      of the disorder. These can include: (1) early life (e.g., genetic or
      environmental) factors; (2) physiological factors including increased motor
      reactivity, visceral hypersensitivity, which may be enabled by postinfectious
      events, and dysregulation of brain-gut communication (e.g., altered central pain
      control mechanisms). In addition, psychosocial factors including psychiatric co
      morbidity, major trauma (e.g., abuse history), and maladaptive coping may amplify
      the clinical expression of the disorder and its outcome. Currently, clinical
      outcome has become understood in terms of global symptom relief and health
      related quality of life.

PMID- 12184144
TI  - [Creatine: the nutritional supplement for exercise - current concepts].
AB  - Creatine, a natural nutrient found in animal foods, is alleged to be an effective
      nutritional ergogenic aid to enhance sport or exercise performance. It may be
      formed in kidney and liver from arginina and glicina. Creatine may be delivered
      to the muscle, where it may combine readily with phosphate to form creatine
      phosphate, a high-energy phosphagen in the ATP-CP system, and is stored. The ATP
      CP energy system is important for rapid energy production, such as in speed and
      power events. Approximately 120 g of creatine is found in a 70 kg male, 95% in
      the skeletal muscle. Total creatine exists in muscle as both free creatine (40%)
      and phosphocreatine (60%). It is only recently that a concerted effort has been
      undertaken to investigate its potential ergogenic effect relative to sport or
      exercise performance. It does appear that oral creatine monohydrate may increase
      muscle total creatine, including both free and phosphocreatine. Many, but not all
      studies suggest that creatine supplementation may enhance performance in high
      intensity, short-term exercise task that are dependent primarily on the ATP-CP
      energy system, particularly on laboratory test involving repeated exercise bouts
      with limited recovery time between repetitions. Short-term creatine
      supplementation appears to increase body mass, although the initial increase is
      most likely water associated with the osmotic effect of increased intramuscular
      total creatine. Chronic creatine supplementation in conjunction with physical
      training involving resistance exercise may increase muscle mass. However,
      confirmatory research data are needed. Creatine supplementation up to 8 weeks,
      with high doses, has not been associated with major health risks; with low doses,
      it was demonstrated that in 5 years period supplementation, there are no adverse
      effects. The decision to use creatine as a mean to enhance sport performance is
      left to the description to the individual athlete.

PMID- 12184145
TI  - [Fatness and fat distribution by social stratum in Venezuelan youths].
AB  - Adiposity and distribution of body fat are important issues in the prediction of
      degenerative diseases. Measurements of weight, height, circumferences of thigh,
      waist and hip; triceps, biceps, subscapular and suprailiac skinfolds; body mass
      index (BMI), centripetal index (CI), waist/hip (WHR), waist/thigh (WTR) ratios
      and sigma skinfold thickness (sigma SK) were performed in 836 youths (373 males,
      463 females) aged 11, 13 and 15 years. Analysis method included Student t test,
      ANOVA, Principal Component Analysis and simple linear regression model, with
      sigma skinfold thickness as independent variable. The sample was divided in two
      groups (A and B) according with Graffar-Mendez Castellano methodology. Sexual
      dimorphism in adiposity and differences in body fat distribution were found with
      a tendency towards peripherical distribution for girls and centripetal for boys.
      Group A (higher stratum) showed higher values of skinfolds in both trunk and
      extremities, and a more peripherical distribution than his peers from group B.
      First component from extremity/trunk and second component from upper/inferior
      trunk distribution explained 40.2% and 32.7% of the variability respectively. CI
      and WHR appear dependent from BMI, WHR showed independence from BMI, although
      significant differences was found by social stratum, reflecting differences in
      fat topography in boys and girls from group B. These results confirm more
      adiposity in group A and a tendency towards central distribution in group B.
      Studies of body fat distribution during these age should include waist/thigh
      ratio.

PMID- 12184146
TI  - [Scales to measure parents and caretakers satisfaction with the food and
      nutrition component of Child care Centers].
AB  - Two Likert-type scales for measuring parents' and caretakers' level of
      satisfaction with the food and nutrition services offered at childcare multi
      centers in a peri-urban community in Caracas, were developed and validated. An
      intentional sample of 20 parents and caretakers were interviewed within the
      naturalistic-constructivist perspective, to capture their perceptions of distinct
      aspects of the food and nutrition components of the program. Categories emerged
      from the interviews that served to construct the items for two scales that
      measure level of satisfaction of parents and caretakers with the food and
      nutrition aspects of the program. To validate the scales, they were applied to 73
      parents and 32 caretakers. Factor and multiple components analysis showed that
      overall, the scales explained 61% and 69% of the variation in level of
      satisfaction of parents and caretakers respectively. Confiability measured with
      Alpha Cronbach coefficient was 0.74 and 0.77 for parents' and caretakers' scales
      respectively. These results reveal scales that have content validity and good
      reliability. Besides, the scales detect specific aspects of the food and
      nutrition service that should be reinforced or modified, to make the Child-care
      Centers program more effective and efficient. External validation of the scales
      is recommended, since they provide an instrument capable of capturing useful
      information for monitoring and evaluating the Child-care Centers program nation
      wide, from the perspective of program managers and parents of program users.

PMID- 12184149
TI  - [Clostridium perfringens in raw and cooked meats and its relation with the
      environment in Costa Rica].
AB  - The presence of Clostridium perfringens in eight slaughter houses from Costa Rica
      was analyzed using the Most Probable Number (MPN) technique, in order to assess
      the risk of acquiring a food borne intoxication due to consumption of
      contaminated meat. C. perfringens was detected in 29 (88%) out of 33 soil samples
      collected from the slaughter house surroundings (average 6.7 x 10(2) MPN/g), as
      well as in 70 (93%) out of 75 intestinal contents of slaughtered animals (average
      3 x 10(4) MPN/g), in 42 (55%) out of 76 samples of slaughtered meat (average 2.2
      x 10(4) MPN/g) and in 30 (61%) out of 49 retail meats (average 8 x 10(3) MPN/g).
      In addition, the presence of this bacterium was evaluated in ten retail meat
      markets located in the Metropolitan Area of Costa Rica, where it was isolated
      from 15 (75%) out of 20 samples of ground meat and from 28 (36%) de 78 stew meat
      samples (average 1.9 x 10(3) and 7.5 x 10(2) MPN/g, respectively). Only one out
      of 35 samples of cooked meat obtained from 32 restaurants that utilize heated
      water baths (average temperature of 82 degrees C) was positive for C. perfringens
      (4 MPN/g, temperature 72 degrees C). Out of 1121 bacterial isolates obtained, 250
      were evaluated for enterotoxigenicity. Only 3 (1.2%) of these tested positive for
      enterotoxin production, probably because most wild strains are not toxin
      producers, even though they can be induced to produce it as a result of repeated
      thermal shocks. The present results urge the adoption of adequate preventive
      measures and high sanitary standards in the meat processing industry in Costa
      Rica, in order to minimize the risk of food-borne intoxications caused by C.
      perfringens, due to its widespread distribution and potential human health
      hazard.

PMID- 12184147
TI  - [Changes in of plasma lipoproteins after the use of palm oil in the diet of a
      group healthy adults].
AB  - Although saturated fat acids have long known to have harmful effects on
      cholesterol and triacylglycerides levels in blood, new concepts have emerged form
      recent research on this matter. The purpose of this study was to know the effect
      of the consumption of palm olein on triacylglycerides and cholesterol levels as
      well as lipoprotein fractions in the blood plasma of healthy individuals from
      both sexes. MATERIALS AND METHODS: Different types of fats were administered for
      12 weeks to 60 subjects, 45 male, 15 female, between 19 and 45 years of age, who
      were divided into three groups: the mix group (MG) was administered oil,
      margarine, and mayonnaise prepared with 50% olein; the olein group (OG) consumed
      fats prepared with 100% olein; and the control group (CG) consumed regular fats
      of customary use by the population. The diets provided 25 to 30% of calories.
      Blood samples were obtained for lipid analysis at the beginning and the end of
      the study. Plasma triacylglycerides and cholesterol concentrations were
      determined by means of enzyme and lipoprotein methods (VLDL, LDL; and HDL) by
      ultracentrifugation. RESULTS AND DISCUSSION: By comparing the groups' means no
      significant differences were found (p > 0.05) in blood lipids. Individual
      differences show a slight increase in VLDL-C in OG compared to MG and CG. No
      differences were found in LDL concentration. CONCLUSIONS: These results
      contribute evidence to differentiate between the effects of saturated vegetables
      oils, such as coconut oil, and of palm olein. The authors recommend not
      extrapolate the effects of type of oil to another in connection with TC increase
      in blood.

PMID- 12184148
TI  - [Effect of pectinase and cellulase addition on in vitro digestibility of common
      bean (Phaseolus vulgaris)].
AB  - Effect of commercial pectinase and cellulase addition on in vitro digestibility
      of two common bean (Phaseolus vulgaris) varieties, black (Brunca) and red
      (Chirripo), was measured. Constant conditions of pH (6.3-6.4), time (60 min), and
      temperature (40 degrees C) were held, and three enzyme concentrations were
      tested: 0.25%, 0.5% and 1.0% m/m. In vitro digestibility increases for black
      beans were 6.9%; 9.5% and 12.3% (p < 0.05), and for red beans were 8.9%; 10.2%
      and 12.9% (p < 0.05), with increasing pectinase concentration. Effects of
      cellulase were dependent upon both, enzyme concentration and bean variety. In
      vitro digestibility of red beans increased by 5.7%; 9.2% and 12.0% with
      increasing cellulase concentration; digestibility of black beans increased by
      less than 5%. No significant difference (p > 0.05) in general acceptance of
      enzyme treated beans (black or red) or nontreated beans was noted.

PMID- 12184150
TI  - [Purification and characterization of proteases from Pseudomonas fluorescens and
      their effects on milk proteins].
AB  - The increase in the levels of psychotropic bacteria in the raw milk during the
      refrigeration period, could lead to the production of heat-resistant enzymes
      responsible for the deterioration of long-life industrial dairy products.
      Pseudomonas fluorescens is the psychotropic bacteria most commonly found in milk
      in Southern Chile. In the present work the enzymatic proteinases extract of
      cultures of Pseudomonas fluorescens RV10 at 6 degrees C in raw milk just milked
      were purified. It was found that the proteases corresponds to a protein with a
      molecular mass of 49.5 kD, that presents heat resistance and rapidly attacks the
      k-casein continuing with the b-casein. It is possible to conclude that storage of
      the milk for long-life products at 6 degrees C is risky, as it causes the loss of
      quality for the proteases of psychotropic bacteria.

PMID- 12184151
TI  - [Protein fraction distribution in milling and screened physical fractions of
      grain amaranth].
AB  - The purpose of the study was to establish the protein distribution based on
      solubility in physical fractions of amaranth flour, in particular between the
      flour from the germ and that from the perisperm. The protein distribution was
      obtained applying a series of solvents sequentially utilized in the classical
      methodology of Osborne & Mendel. The sample of A. cruentus weighing 2000 g was
      divided into 4 subsamples of 500 g each. One was left as the control while the
      other 3 were ground individually with a mill. Each flour was screened through 18,
      20, 30 and 40 mesh screens, so that 5 fractions were obtained from each of the
      whole grain flours. Samples of each screened fractions were observed by
      stereoscopy and analyzed for moisture, fat and protein. This characterization
      suggested that the fraction above the 30 mesh screen and the flour which passed
      the 40 mesh screen probably were the perisperm and germ respectively. The 30 mesh
      sample contained 2.34 fat and 9.05% protein while the 40 mesh contained 16.18%
      fat and 26.46% protein. The extraction and partitioning of the proteins indicated
      that the most important fractions in germ and perisperm were the water soluble
      and glutelins measured by Kjeldahl. The relationship of the water soluble +
      globulin to glutelins ratio was 2.1 to 1 in the whole grain, 1.9 to 1 in the
      perisperm and 1.7 to 1 in the germ. The distribution of proteins was very much
      alike between germ and perisperm. The levels of prolamines were quite low. The
      protein extraction of the perisperm proteins retained on the 30 mesh screen was
      low (71.1%) measured by Kjeldahl and 47.4% with the Bradford method to measure
      protein.

PMID- 12184152
TI  - [Physical, culinary and nutritional characterization in dry bean from the
      highlands of Mexico].
AB  - In the improvement of a given crop species, knowledge on the grain quality and
      related traits in the progenitors used in the breeding process is needed to
      establish their usefulness as a source of a given character, and as well as to
      plan the proper combinations between progenitors. The aim of the present research
      was to characterize a group of 49 genotypes of Phaseolus vulgaris and one of
      Phaseolus coccineus, in relation to physical, cooking and nutritional grain
      traits. Cultivar Blanco Tlaxcala (P. coccineus) showed a larger grain size and
      lower protein content than any of the P. vulgaris cultivars. The 86% of the
      studied genotypes showed cooking times lower to 115 min, and a significant
      correlation between this trait and water sorption capacity (r = 0.78 **) was
      found. Cultivars Redlands Pioneer and ICA Zerinza could be used as source of low
      cooking time; and Perry Marrow, Kaboon and ICA Zerinza in the production of low
      shell content cultivars. Genotypes G 2333, Negro Lolotla, REN 27 and J 117 showed
      the highest grain protein content. On the other hand, BY 94022, Pinto Villa and
      Negro 150 had the lowest trypsin inhibitor activity. Results support the possible
      use of the above genotypes as sources of those grain traits. In general, large
      variability was found for most of the quality traits determined; therefore, there
      is scope for improvement through recombination and selection.

PMID- 12184153
TI  - [Stability of anthocyanins in pasteurized juice of blackberry ((Rubus glaucus
      benth].
AB  - In this research the chemical stability of total anthocyanins in three
      pasteurized juices elaborated from 12% of blackberry (Rubus glaucus Benth) pulp,
      and addition of ascorbic acid (Formulation A: 0.1%, Formulation B: 0.05% and
      Formulation C: 0.01%), was evaluated by means of absorption visible spectra (400
      580 nm). Physicol-chemical characterization (acidity, soluble solids content in
      degree Brix, pH), and count of mesophilic microorganism, fungi, yeasts, fecal
      coliforms (PMN/mL) and Escherichia coli, were evaluated. Sensorial parameters
      (color, smell, flavor) were investigated by means of un-trained panel using a
      hedonic scale (Fridman, P < 0.05). The study was performed during storage for 9
      days. The total anthocyanins were reported as pelargonidin-3-glycoside g/L, and
      no significant differences were founded among the evaluated in each formulation
      during storage (P > 0.05). Bactocromic effect due to oxidation as not observed.
      Acidity (6.0-7.2 mL NaOH 0.079 N), soluble solids content (9.0-9.8 degrees Brix)
      and pH (3.4) did not show significant differences (P > 0.05). The microbiological
      evaluation showed minimum values for pasturized products (fungi CFU/mL < 10,
      yeast CFU/mL < 10, fecal coliforms CFU/mL < 10 and mesophilic microorganism
      CFU/mL between 120-140 on first day in storage). Sensorial analysis did not show
      significant differences (Fridman, P > 0.05).

PMID- 12184154
TI  - [Effect of blanching and hygroscopic coating on quality of fresh cut carrots
      (Daucus carota var. chantenay) during storage].
AB  - The effect of blanching at low temperatures (solution 1% acid citric, 50 degrees
      C for 30 seconds) and the application of glycerol as humectant (3% p/p, 20
      seconds) to preserve the quality of fresh-cut carrots (Daucus carota) were
      studied as individual or combined treatments. Four treatments were evaluated: a
      control by dipping samples for 30 seconds in distilled water (T1); blanching
      (T2); glycerol application (T3); and blanching plus glycerol application (T4).
      Total carotenoids content, color, soluble solids and weight loss were monitored
      during storage. Results showed no differences between treatments in carotenoids
      content (p > 0.10) and soluble solids (p > 0.05). However, differences were
      observed between treatments in weight loss (p < 0.05) and color change (p <
      0.05). Blanched samples (T2 and T4) showed small changes in orange color
      intensity compared to treatments T1 and T3 (p < 0.05).

PMID- 12184155
TI  - [Essential and non essential amino acid content of infant cereals in different
      stages of industrial processing and its relationship with chemical scores of
      protein quality].
AB  - The effect of technological process on essential and non essential amino acids
      contents in infant cereals, the protein and essential amino acids infant dietary
      requirements cover by infant cereals, and its quality using some chemical scores
      has been studied. Mix of raw flours, mix of roasted flours, mix of enzymatically,
      hydrolysed and drum dried flours and commercial infant cereals of four different
      types of infant cereals: "Multicereal" and "Wheat" (both with gluten), "Growth"
      and "Rice and carrot" (both gluten free) were evaluated. The technological
      process only show a significant effect on lysine, arginine (P < 0.05) and valine
      (P < 0.01) contents in "Rice and carrot" infant cereal. Protein of any studied
      infant cereals covers 17.4% of the daily infant requirements in, while for
      essential amino acids will cover about 25 to 200% until the third year of life.
      As we expected, the limitant amino acid was lysine in all flours. Chemical scores
      only were affected by technological treatment in "Rice and carrot" infant cereal,
      showing the gluten-free infant cereals higher values (36.7-69.5%) than gluten
      infant cereals (18.1%-30.7%) at the end of the processing. It should be standing
      out "Growth" infant cereal, because of it has a higher lysine content than other
      infant cereals due to the main ingredients rice and corn.

PMID- 12184156
TI  - Cholesterol and fatty acids profile of Brazilian commercial chicken giblets.
AB  - This study was carried out to determine the chemical composition, cholesterol
      contents and fatty acids profile of Brazilian commercial chicken giblets. The
      analysis were performed in gizzard, liver and heart in natura and also in cooked
      gizzard, fried liver and roasted heart. Fat and cholesterol contents ranged from
      0.88% and 72.68 mg/100 g, in cooked gizzard, to 22.19% and 213.18 mg/100 g, in
      roasted heart. As the fat content gets higher, so does the cholesterol content.
      Palmitic (C16:0) and stearic acids (C18:0) were the predominant saturated fatty
      acids (SFA). The C16:0 ranged from 6.39% in cooked gizzard to 18.51% in fried
      liver. The C18:0 level ranged from 6.62% in roasted heart to 19.19% in cooked
      gizzard. Linoleic acid (C18:2 omega 6) was the predominant polyunsaturated fatty
      acid (PUFA). The data revealed that the three different analysed giblets
      presented a good PUFA/SFA ratio, with values of 1.11, 1.14 and 1.40 for cooked
      gizzard, fried liver and roasted heart, respectively.

PMID- 12184157
TI  - [Characterization of the lipid portion of pink shrimp commercial samples].
AB  - The objective of this study was to describe the fresh cooled pink-shrimp (Penaeus
      brasiliensis and Penaeus paulensis) lipid. The total lipid content was 1.13 +/-
      0.09 g/100 g while fatty acid profile showed 32.9% saturated, 20.4%
      monounsaturated and 40.5% polyunsaturated. Eighteen fatty acids were detected,
      seven saturated (14:0, 15:0, 16:0, 17:0, 18:0, 20:0, 22:0), four monounsaturated
      (16:1w7, 17:1w9, 18:1w9, 20:1w9) and seven polyunsaturated (18:2w6, 18:3w3,
      20:2w6, 20:4w6, 20:5w3, 22:5w3, 22:6w3). The free cholesterol content was 92 to
      136 mg/100 g with average of 118 mg/100 g. In same time, was observed the
      occurrence of free 7-ketocholesterol, a product of cholesterol oxidation, in
      levels of 0.185 to 0.366 microgram/g. The fatty acid profile was obtained by gas
      chromatography with a fused silica column Supelcowax 10. The cholesterol and 7
      ketocholesterol was determined by high performance liquid chromatography using a
      mu-Porasil column, normal phase, and a diode array detector.

PMID- 12184158
TI  - [Protein-energy malnutrition in the gastrectomized patient].

PMID- 12184159
TI  - [Hepatopulmonary syndrome in liver transplantation candidates].
AB  - BACKGROUND: Hepatopulmonary syndrome is an important clinical problem associated
      with chronic liver disease. Liver transplantation can result in complete
      resolution of the arterial hypoxemia associated with this syndrome, even in its
      most severe presentation. AIM: To determine the prevalence of hepatopulmonary
      syndrome in adult liver transplant candidates. PATIENTS AND METHODS: Fifty-four
      consecutives adult patients (> or = 18 years) with severe liver disease waiting
      for liver transplant were screened for arterial hypoxemia (PaO2 < 70 mm Hg) while
      they were seated, at rest, and breathing room air. Patients with arterial
      hypoxemia underwent contrast-enhanced two-dimensional echocardiography and
      pulmonary function testing. Hypoxemia (PaO2 < 70 mm Hg) was present in 7 of 54
      patients (12.9%), although only 1 of them complained of dyspnea. The Child's
      classification of the patients were: A = 1, B = 4, and C = 1. All seven hypoxemic
      patients had positive contrast-enhanced two-dimensional echocardiography,
      consistent with hepatopulmonary syndrome. CONCLUSION: The prevalence of
      hepatopulmonary syndrome in adult liver transplant candidates is elevated. The
      screening for hepatopulmonary syndrome should be part of the routine evaluation
      of liver transplant candidates even in the absence of pulmonary symptoms.

PMID- 12184160
TI  - [CA72-4 and CEA in serum and peritoneal washing in gastric cancer].
AB  - BACKGROUND: The treatment and the prognosis of gastric cancer patients depends
      mainly on clinical stage. Serum and peritoneal tumoral markers levels can be
      helpful to evaluate individual risk for recurrence. AIMS: To evaluate the
      sensibility of the tumoral markers in the serum and in the peritoneal washing on
      diagnosis of gastric cancer. PATIENTS AND METHODS: Forty patients with
      adenocarcinoma of the stomach (11 stage I or II and 29 III or IV) and 24 patients
      with benign diseases were studied prospectively. All of them were submitted to
      laparotomy. Blood and peritoneal washed was collected during surgery before
      tumoral resection, for determination of CEA and CA72-4. RESULTS: CEA and CA 72-4
      serum levels were elevated in 25% and 47.5% respectively. Through the curves ROC,
      we defined the cut-off values for the markers in washed peritoneal fluid. Through
      these values CEA and CA72-4 rose in 60% and 57.5% respectively. The values of CEA
      and of CA 72-4 in the serum and in washed peritoneal fluid were higher in cancer
      patients stage III and IV. CEA levels in the peritoneal washed fluid were higher
      in the patients with tumor T3-4. Washed peritoneal CA72-4 differed the control
      group from the cancer group. CONCLUSION: CA72-4 was the most sensitive marker in
      the serum of the patients with gastric cancer. Otherwise in the washing
      peritoneal fluid the most sensitive marker was CEA. These levels were higher in
      patients with surpass the serosa and lower in patients with mucosa or muscular
      tumors.

PMID- 12184161
TI  - [The importance of AST / ALT rate in nonalcoholic steatohepatitis diagnosis].
AB  - BACKGROUND/AIMS: There is a histologic similarity between nonalcoholic
      steatohepatitis and alcoholic liver disease and in some cases differential
      diagnosis may be difficult, since some patients do not report abusive alcohol
      consumption. OBJECTIVE: Evaluating the usefulness of setting the rate AST/ALT for
      the differential diagnosis of nonalcoholic steatohepatitis and alcoholic liver
      disease. PATIENTS AND METHODS: Twenty nine obese patients with nonalcoholic
      steatohepatitis were compared with 28 patients with alcoholic liver disease. The
      diagnosis of nonalcoholic steatohepatitis was made after exclusion of other
      causes of liver disease and by histologic findings of, at least, macrovesicular
      steatosis and hepatocellular necrosis. RESULTS: In patients with nonalcoholic
      steatohepatitis the medium AST value was 52.3 +/- 21.2 U/L and ALT of 90.1 +/-
      37.9 U/L, being the AST/ALT rate lower than 1 in all patients. In patients with
      alcoholic liver disease the medium AST value was 140 +/- 82.5 U/L and ALT was
      50.6 +/- 40.3 U/L. The rate was higher than 1 in all cases and higher than 2 in
      24 (85.7%), being statistically significant when compared with patients with
      nonalcoholic steatohepatitis. CONCLUSION: The AST/ALT rate seems to be useful in
      the differential diagnosis of liver diseases, while lower than 1 is highly
      suggestive of nonalcoholic steatohepatitis.

PMID- 12184162
TI  - [Serum gamma-glutamyltransferase alteration in hepatic schistosomiasis doesn't
      correlate with parasitic load and precedes ultrasound alterations].
AB  - BACKGROUND: Liver disorders are the major manifestations of schistosomiasis
      mansoni. Factors that account for increased concentrations of cholestasis
      indicating enzymes in the hepatosplenic form of the disease are unknown.
      OBJECTIVE: To assess the correlation between increased gamma-glutamyltransferase
      serum levels and both the parasitic load and ultrasound alterations in patients
      with schistosomiasis. PATIENTS AND METHODS: Twenty-five patients with the chronic
      form of schistosomiasis were assessed for the presence or absence of increased
      enzymatic levels, for the parasitic load (low x medium/high) and for ultrasound
      parameters. Furthermore, analysis of prothrombin time and a platelet count were
      performed. RESULTS: Of the 25 patients, 13 showed increased gamma
      glutamyltransferase plasma levels. No significant correlation was found between
      increased gamma-glutamyltransferase levels and the parasitic load, or between
      increased enzyme levels and ultrasound alterations. Nor did the prothrombin index
      or the platelet count differ between the two groups (normal gamma
      glutamyltransferase levels and increased gamma-glutamyltransferase levels).
      CONCLUSION: The parasitic load explains no rise in gamma-glutamyltransferase
      plasma levels in patients with the chronic form of schistosomiasis, and
      conventional ultrasound is not a sensitive method to detect the alteration
      suggested by the increased enzyme level in those patients.

PMID- 12184163
TI  - [Protein-energy malnutrition in the gastrectomized patient].
AB  - BACKGROUND: Gastrectomy leads to nutritional consequences that although expected,
      are not usually measured due to methodological limitations. AIM: To assess the
      protein-energy deficiency degrees estimated by isolated or combined indicators.
      PATIENTS AND METHODS: There were studied 71 patients, who had undergone partial
      (n = 53) or total (n = 18) gastrectomy in the last 6-24 months (M1) or 24-60
      months (M2). The dietary intake, body composition and biochemical data were
      estimated and compared between groups and moments. RESULTS: The surgeries were
      undertaken after complications of peptic ulcer (68%) or due to gastric cancers
      (32%). Weight loss was referred by 70% of patients and higher (16 +/- 5 x 10 +/-
      6 kg) in total gastrectomy group. The patients showed anthropometric deficits
      along with normal albumin and low energy intake, suggesting chronic-energy
      deficiency. Hematocrit, hemoglobin and iron showed the most prominent reductions.
      Anemia was installed earlier and worsened in the total gastrectomy group. Thus,
      when combining hemoglobin + albumin, + total lymphocyte count + arm circumference
      and subscapular skinfold, the protein-energy deficiency prevalence was higher and
      more severe than when hemoglobin was omitted. The protein-energy deficiency
      occurred earlier and it was more severe in total gastrectomy patients, while in
      partial gastrectomy the protein-energy deficiency increased in the late post
      operative period. CONCLUSION: The protein-energy deficiency resulted from
      gastrectomy is more marasmus-like coarsing with anemia, both installed earlier
      and severer in total gastrectomy than partial gastrectomy but ending up similarly
      at the late postoperatory.

PMID- 12184164
TI  - Angiogenesis in advanced colorectal adenocarcinoma with special reference to
      tumoral invasion.
AB  - BACKGROUND: Angiogenesis is a crucial step in tumor growth and progression. Its
      quantification by microvessel counting has a prognostic value in several types of
      malignancies and recently has been appraised in gastrointestinal tumors. AIM: To
      assess the prognostic significance of microvessel quantification in colorectal
      carcinomas, studying its association with hematogenous metastases, survival and
      clinicopathological variables such as size, histologic differentiation and depth
      of tumoral invasion. PATIENTS/METHODS: Forty eight patients with colorectal
      adenocarcinoma were included in this study. Histologic sections of invasion
      tumoral margin (4 microns) were analyzed and endothelined microvessels were
      immunostained with monoclonal mouse Von Willebrand Factor (anti-FVIII). The
      microvessel count was performed from the identification of the area with
      increased microvessel density--hot spots--and results of the mean in five of
      these fields. RESULTS: The cut-off microvessel count was 14 microvessels/0.785
      mm2, which divided the sample into hypovascular and hypervascular groups. While
      2/8 (25%) tumors with muscularis propria invasion were classified as
      hypervascular, 11/15 (73%) tumors with serosa or perivisceral fat were classified
      as hypervascular. However, a non-significant statistical association was found
      between the angiogenesis quantification, hematogenous metastases, survival and
      clinicopathological variables such as size and histologic differentiation of the
      tumor. CONCLUSIONS: The findings of significantly increase of microvessel count
      in conformity with tumoral invasion depth supports the hypothesis that tumor
      progression might be related to angiogenesis. Although angiogenesis is an
      important step in the tumoral growth and during the metastatization process,
      other factors can be implicated.

PMID- 12184165
TI  - Study of morbidity in orthotopic small intestine transplantation with Wistar
      rats. Experimental study.
AB  - BACKGROUND: Transplantation of the small intestine is a surgical procedure
      currently under investigation for its possible application in the treatment of
      patients with short bowel syndrome, aiming at the reintroduction of an oral diet.
      AIM: To define the morbidity and mortality of intestinal transplantation in small
      animals using microsurgery. Intra and postoperative morbidity and mortality were
      studied in Wistar rats submitted to orthotopic intestinal allotransplantation.
      MATERIAL AND METHOD: The animals were divided into three groups: group A (37
      donor animals), group B (37 recipient animals), and group C (10 control animals).
      Group B was divided into three subgroups according to survival time. Subgroup TI
      consisted of animals that died during surgery or due to causes directly related
      to surgical intervention, subgroup T2 consisted of animals that died between the
      4th and 29th postoperative day, and subgroup T3 consisted of animals that
      survived after 30 days. Transplanted animals were evaluated in terms of surgical
      technique used (vascular and intestinal anastomosis), graft quality, surgical
      time, and clinical parameters. The animals that died by the 29th postoperative
      day were submitted to autopsy and the remaining ones were sacrificed after 30
      days. RESULT: There was a high rate of complication of a surgical nature. Early
      mortality rate, i.e., mortality up to the third postoperative day, was 54% with
      vascular anastomosis being the major cause of death. Surgical time was evaluated
      in a restricted and homogeneous group and showed a strong prognostic value in
      terms of successful transplantation. Clinical parameters such as weight loss,
      reduction of ingestion, reduction of motor activity and diarrhea were directly
      correlated with acute rejection. CONCLUSION: The experimented intestinal
      transplant is a procedure companied by considerable morbidity and mortality due
      to surgical complications in postoperative period, vascular anastomosis and total
      surgical time.

PMID- 12184166
TI  - [Immunonutrition in experimental colitis: beneficial effects of omega-3 fatty
      acids].
AB  - BACKGROUND: Recent data have given emphasis to the benefits of immunonutrition
      with omega-3 fatty acids (n-3 FA) in various clinical situations. This work
      presents the results of parenteral administration of different lipid emulsions in
      experimental acute colitis and reviews the pertinent literature. METHODS: Seventy
      four adult male Wistar rats were randomized in six groups that had 10% acetic
      acid-induced colitis (except CS). During 7 days, control groups CS (without
      colitis) and CC (with colitis) received physiological solution and the others
      received specific lipid emulsion by a central venous catheter (0.5 mL/h). The n
      3/n-6 FA ratio and lipidic compositions were: group L--1:7.7 (LCT, n = 12), M-
      1:7.0 (MCT and LCT, n = 12), LW-3--1:4.5 (LCT plus FO, n = 12) and MW-3--1:3.0
      (MCT and LCT plus FO, n = 13). Rats were evaluated to assess abdominal and
      intestinal alterations, macrophage cellularity and colonic concentrations of
      LTB4, LTC4, PGE2 and TXB2. RESULTS: N-3 FA treated rats (LW-3 and MW-3) presented
      less inflammatory abdominal alterations than CC rats. Mucosal ulcer formation in
      MW-3 group was the only comparable to CS group. Only CS, M and MW-3 rats
      presented smaller cellularity than CC group. Comparing to CC group, there were
      found smaller averages of LTB4 in CS, LW-3 and MW-3 groups, of PGE2 in CS, M and
      MW-3 groups, and of TXB2 in CS and MW-3 groups. LTC4 averages were not different.
      CONCLUSIONS: 1) LCT-containing lipid emulsion with low n-3/n-6 ratio do not
      modify inflammatory colitis derived manifestations; 2) the association of MCT/LCT
      containing lipid emulsion with fish oil with high n-3/n-6 ratio impels great
      beneficial impact, attenuating morphological and inflammatory consequences and
      decreasing colonic concentrations of proinflammatory mediators.

PMID- 12184167
TI  - [Aspects of sleep effects on the digestive tract].
AB  - BACKGROUND: During sleep the gastrointestinal system function is markedly reduced
      most of the time. OBJECTIVES: In this revision we described the effect of sleep
      on the digestive system. Salivation, swallowing rate, upper esophageal sphincter
      pressure and number of primary esophageal contractions have all been shown to be
      reduced during sleep. DATA SOURCES: Gastric emptying is slow during sleep but the
      REM sleep is associated with faster gastric emptying. During the night we have a
      more regular intestinal motility than during the day. During sleep, phase II of
      the migrating motor complex cycle is virtually absent, both during diurnal or
      nocturnal sleep. The nocturnal velocity of migrating motor complex propagation in
      the proximal small bowel is slower than the diurnal velocity. The colon has a
      decrease in tonus and contractions. The anal canal pressure is lower and rectum
      activity is higher during sleep than during the awake state, but the anal
      pressure is still higher than the rectum pressure and the rectum contractions are
      most frequently retrograde. DATA SYNTHESIS: Transient lower esophageal sphincter
      relaxation is the most frequent cause of gastroesophageal reflux. The frequency
      of this transient relaxation is very low during sleep. Gastroesophageal reflux
      during sleep is more frequently associated with a low lower esophageal sphincter
      pressure. CONCLUSIONS: In this situation the disease is worse because the patient
      is in the supine position, so gravity does not help the acid esophageal
      clearance, salivation is decreased and the primary esophageal contraction is not
      frequent, a fact causing a prolongation of acid clearance during sleep. The right
      lateral position during sleep causes more reflux episodes than the left lateral
      position. The gastroesophageal reflux may be associated with nocturnal wheezing,
      chronic nocturnal cough and sleep apnea.

PMID- 12184168
TI  - [Evaluation of efficacy, safety and tolerability rabeprazole in treatment of acid
      peptic diseases ].
AB  - BACKGROUND: Rabeprazole, a substituted benzimidazole, represents a new generation
      of proton pump inhibitors that has recently been approved by the FDA and European
      Union for treatment of acid-related diseases. OBJECTIVES: To assess the efficacy
      and tolerability of rabeprazole 20 mg in actual conditions of use in everyday
      clinical practice on subjects with diagnosis of erosive gastroesophageal reflux
      disease and/or gastric and/or duodenal ulcer. PATIENTS/METHODS: A total of 171
      outpatients (55% men, 45% women) with a mean age of 42.5 years were enrolled in
      this trial. The majority of subjects (81.0%) were Caucasians. Patients with
      endoscopically confirmed erosive/ulcerative gastroesophageal reflux disease
      (Savary-Miller classification), duodenal ulcer and/or benign gastric ulcer were
      eligible to receive rabeprazole 20 mg once daily for 4 to 8 weeks, depending on
      the diagnosis and at investigators' discretion. Patients were requested to record
      their symptoms in a diary card in a daily basis. RESULTS: One hundred and sixty
      two patients completed the study in accordance with the protocol. Reflux
      esophagitis was diagnosed in 78 (48.1%) patients, duodenal ulcer in 39 (24.1%)
      and gastric ulcer in 24 (14.8%). Eleven (6.8%) patients presented reflux
      esophagitis associated with duodenal ulcer and 7 (4.3%) associated with gastric
      ulcer. Finally, 3 (1.9%) presented both gastric and duodenal ulcer. Fifty-three
      percentage of patients were free of symptoms on the first day of treatment and
      89.5% after a week. The healing rate was 84.4% for patients with reflux
      esophagitis, 90.6% for duodenal ulcer and 90.9% for gastric ulcer. The adverse
      effects were minimal and transitory. CONCLUSIONS: Rabeprazole is highly effective
      and well tolerated in acute healing of reflux esophagitis and peptic ulcers. In
      addition, it provides fast symptoms relief.

PMID- 12184170
TI  - Development of an analytical method for the determination of betaines in higher
      plants by capillary electrophoresis at low pH.
AB  - In recent years the role of betaines in higher plants has been extensively
      investigated in relation to environmental stress response. This paper reports the
      establishment of a simple, rapid and reliable method for the determination of
      betaines using capillary electrophoresis (CE) at low pH. Betaines were first
      converted to their phenacyl esters and the crude reaction mixture was then
      applied directly to CE without any pre-treatment. Employing an electrolyte
      running solution at pH 3 gave a well-resolved electropherogram for the esters of
      glycine betaine (1), trigonelline, proline betaine, gamma-butyro betaine, and
      carnitine. The content of 1 and its variation in plant samples collected from
      high-salinity areas in north China and west Australia are presented.

PMID- 12184169
TI  - [Breath methane in children with chronic constipation].
AB  - RATIONALE: Methane is an intestinal gas which may be excreted in the expired air
      of about 10% of children. OBJECTIVE: The aims of this study were to investigate
      methane production by children with functional chronic constipation and methane
      concentration in the expired air before and after a bowel movement induced by a
      phosphate enema. METHODS: Seventy-five patients with functional chronic
      constipation aged from 3 to 13 years were studied. Methane concentration in the
      expired air was determined using a gas chromatograph (Quintron, model 12i).
      Methane production was considered present if the breath methane concentration was
      equal or greater than 3 ppm. RESULTS: Methane production was present in 44
      (86.3%) of 51 patients with constipation and fecal soiling versus only 7 (29.2%)
      of 24 patients with constipation without fecal soiling. After six weeks of
      therapy for constipation, the number of methane producers decreased by 65.2%.
      None of the 10 children with normal intestinal habit produced methane. Expired
      air methane concentration was determined before and after a bowel movement
      induced by a phosphate enema in 20 patients with impacted stool. From these 20
      patients, 12 were methane producers. The median (percentiles 25 and 75 between
      parenthesis) of methane concentration decreased from 21.5 (15.0-25.5) ppm before
      to 11.0 (4.0-12.5) ppm after the bowel movement. CONCLUSION: Methane production
      was associated with chronic constipation with soiling and decreased when impacted
      stool decreased.

PMID- 12184171
TI  - Rapid method for determining malondialdehyde as secondary oxidation product in
      palm olein system by Fourier transform infrared spectroscopy.
AB  - A simple and rapid Fourier transform infrared (FTIR) spectroscopic method has
      been developed for the quantitative determination of malondialdehyde as secondary
      oxidation product in a palm olein system. The FTIR method was based on a sodium
      chloride transmission cell and utilised a partial least square statistical
      approach to derive a calibration model. The frequency region combinations that
      gave good calibration were 2900-2800, and 1800-1600 cm-1. The precision and
      accuracy, in the range 0-60 mumol malondialdehyde/kg oil, were comparable to
      those of the modified distillation method with a coefficient of determination
      (r2) of 0.9891 and standard error of calibration of 1.49. The calibration was
      cross-validated and produced an r2 of 0.9786 and standard error of prediction of
      2.136. The results showed that the FTIR method is versatile, efficient and
      accurate, and suitable for routine quality control analysis with the result
      obtainable in about 2 min from a sample of less than 2 mL.

PMID- 12184172
TI  - Characterisation of new oligoglycosidic compounds in two Chinese medicinal herbs.
AB  - A series of caffeic acid derivatives (3,5-dicaffeoyl-quinic acid, 3,4-dicaffeoyl
      quinic acid, and 4,5-dicaffeoyl-quinic acid), and the new compound beta,3,4
      trihydroxyphenethyl-O-[beta-apiofuranosyl-(1-->4)-alpha- rhamnopyranosyl-(1-->3)]
      (4-O-caffeoyl)-beta-glucopyranoside (wedelosin), as well as three known flavonoid
      glycosides (quercetin 3-O-beta-glucoside, kaempferol 3-O-beta-apiosyl-(1-2)-beta
      glucoside, and astragalin or kaempferol 3-O-beta-glucoside) were isolated from
      the Chinese medicinal herb Wedelia chinensis. Wedelosin showed an inhibitory
      activity on both the classical and the alternative activation pathway of the
      complement system. Another Chinese medicinal herb, Kyllinga brevifolia, yielded
      two known flavonoid glycosides [kaempferol 3-O-beta-apiosyl-(1-2)-beta-glucoside
      and isorhamnetin 3-O-beta-apiosyl-(1-2)-beta-glucoside], and a new quercetin
      triglycoside [quercetin 3-O-beta-apiofuranosyl-(1-->2)-beta-glucopyranoside 7-O
      alpha-rhamnopyranoside]. The latter compound showed a moderate anti-viral
      activity.

PMID- 12184173
TI  - Quantitative determination of oleane derivatives in Terminalia arjuna by high
      performance thin layer chromatography.
AB  - A simple, precise and rapid high performance thin layer chromatographic method
      has been developed for the simultaneous quantitative determination of five oleane
      derivatives, namely, arjunic acid, arjunolic acid, arjungenin, arjunetin and
      arjunglucoside I from stem bark extract of Terminalia arjuna. The isolation and
      separation of these compounds was carried out on 60F254 layers eluted with
      chloroform:methanol (90:10), and the analytes were visualised through colour
      development with vanillin in concentrated sulphuric acid:ethanol. Scanning and
      quantification of the spots at 640 nm showed good recoveries in the range 96.40
      101.7%.

PMID- 12184174
TI  - High-performance liquid chromatographic analysis of genistein and other
      isoflavonoids from heartwood of Ougeinia dalbergioides.
AB  - A simple binary gradient HPLC method employing a Symmetry C18 column is described
      for the analysis of genistein, ougeinin, homoferririn, 2',4',5,7-tetrahydroxy-6
      methyl isoflavone and 2',4',8-trihydroxy-6-methoxy-7-methyl isoflavone present in
      heartwood extract of Ougeinia dalbergioides.

PMID- 12184175
TI  - Detection of polyhydroxyalkaloids in Lonchocarpus extracts by GC-MS of acetylated
      derivatives.
AB  - The methanol extracts of the roots of Lonchocarpus cultratus, L. latifolius and
      L. subglaucescens, species native to Brazil, were all active in the brine shrimp
      lethality test. Fractions rich in polyhydroxylated alkaloids were obtained from
      these extracts and, following acetylation, were analysed by GC-MS leading to the
      identification of acetylated derivatives of 2,5-trans-dihydroxymethyl-3,4-trans
      dihydroxypyrrolidine (1), 1-deoxymannojirimycin, 1-deoxynojirimycin, fagomine and
      homonojirimycin. Only from L. subglaucescens could a compound with the
      constitution and relative configuration expected for the penta-acetate of 1 be
      isolated, and its molecular structure was determined for the first time through
      extensive spectral data analysis.

PMID- 12184176
TI  - Determination of andrographolide, deoxyandrographolide and neoandrographolide in
      the Chinese herb Andrographis paniculata by micellar electrokinetic capillary
      chromatography.
AB  - In this paper a micellar electrokinetic capillary chromatographic (MEKC) method
      has been developed for determining the active components (andrographolide,
      deoxyandrographolide and neoandrographolide) in water:ethanol extracts of the
      Chinese crude herb Andrographis paniculata and its preparations (Chuanxinlian and
      Xiaoyan Lidan tablets). The optimum separation conditions were 15 mM sodium
      dodecyl sulphate in 30 mM borate buffer (pH 9.5) with UV detection wavelength at
      214 nm and a constant voltage of 16 kV. An HPLC method was employed in order to
      validate the MEKC method with respect to separation efficiency, sensitivity,
      linearity and repeatability. The two methods are shown to be complementary
      because of their different selectivity and thus are very suitable for cross
      validation studies. The MEKC method is demonstrated to be more appropriate for
      the analysis of the active compounds in A. paniculata in that it is easier and
      less expensive to use and does not suffer from contamination of the
      chromatographic column.

PMID- 12184177
TI  - Direct analysis of abscisic acid in crude plant extracts by liquid chromatography
      -electrospray/tandem mass spectrometry.
AB  - A new method, based on liquid chromatography--electrospray/tandem mass
      spectrometry, for the determination of abscisic acid (ABA), an essential plant
      hormone that regulates key metabolic pathways and responses to environmental
      cues, has been developed. Substantial changes in extraction procedures are also
      proposed. Data indicate that the organic solvents classically used as extraction
      buffers can be substituted by an aqueous solution, resulting in the same amounts
      of extracted ABA. The new method, which uses minute amounts of plant tissue, has
      an estimated limit of detection below 50 pmol ABA/g, and the sensitivity of the
      technique allows the analysis of ABA in crude plant extracts. Overall, this new
      rapid, sensitive and accurate procedure to determine ABA will allow analysis of
      multiple samples in a short time and represents a clear advantage in comparison
      with the conventional procedures involving many preparative steps and large
      amounts of plant tissue.

PMID- 12184178
TI  - High-performance capillary electrophoresis analysis of mate infusions prepared
      from stems and leaves of Ilex paraguariensis using automated micellar
      electrokinetic capillary chromatography.
AB  - An automated micellar electrokinetic capillary chromatographic method has been
      developed in order to determine xanthines, e.g. caffeine, theobromine and
      theophylline, and chlorogenic acid in samples of yerba mate (Ilex
      paraguariensis). The target constituents were detected by photodiode array, and
      quantified by an external standard method. In addition, each constituent was
      collected separately and identified by EIMS. The method has been used to analyse
      30 samples of mate infusions prepared at 30 and 75 degrees C with milled leaves
      and stems of 14 commercial brands which had been subjected to different
      elaboration processes. Suspended powdered material of each infusion was also
      analysed after three sieving steps. There was a remarkable difference in the
      relative xanthine composition of the finely suspended material, the amount of
      which varied according to the yerba mate brand, the elaboration process and the
      temperature of the infusion. The importance of these results with respect to
      gastrointestinal disorders which have been observed by habitual consumers of mate
      are discussed.

PMID- 12184179
TI  - British RNs warn on perils of social security privatization.

PMID- 12184180
TI  - The provider matters.

PMID- 12184181
TI  - Feeding frenzy.

PMID- 12184182
TI  - 'High touch,' not high tech.

PMID- 12184183
TI  - An interview with Elena Masforroi Rosales, RN.

PMID- 12184184
TI  - Inner visions. The path to nursing in inner-city neighborhoods.

PMID- 12184185
TI  - Deskilling battle heats up in California.

PMID- 12184186
TI  - Study: U.S. pays 60 percent of health care costs.

PMID- 12184187
TI  - [Evidence of enterotoxins and toxic shock syndrome toxin (TSST-1) in strains of
      Staphylococcus aureus isolated from various biological materials].
AB  - Among 413 strains of S. aureus isolated from patients with chronic staphylococcal
      infections, from haemocultures in bacteriaemia and septic conditions, from
      gynaecological materials and nasal plugs of healthy carriers the authors detected
      the production of one or several types of enterotoxins in 124 strains (30.0%),
      production of TSST-1 in 19 strains (4.6%) and the concurrent production of
      enterotoxins and TSST-1 in 38 strains (9.2%). The highest ratio of toxigenic
      strains of S. aureus was found in departments (51.4%) and from hospitalized
      patients in blood cultures in bacteriaemias and septic conditions (41.2%). In a
      group of 184 strains from patients with chronic staphylococcal infection toxin
      production was proved in 49 strains (26.6%). Of 74 strains of S. aureus isolated
      from healthy carriers there were 16 toxigenic strains (21.6%). The most frequent
      type of enterotoxins were enterotoxins type A (26.7%) and C (24.4%). 21 strains
      (24.4%) produced more than one type of enterotoxins.

PMID- 12184188
TI  - [Effect of culture media on surface and enzymatic activity in Klebsiella
      species].
AB  - The effect of three complex media (KM) [Mueller-Hinton broth (MHB), brain heart
      infusion (MSI) and proteose peptone (PP)] and one mineral medium (MM) on surface
      and enzyme activities of five strains Klebsiella species was studied. Klebsiella
      oxytoca and Klebsiella ornithinolytica had a marked hydrophobic character after
      growth in MHB, MSI and MM, Klebsiella terrigena only in PP. K. oxytoca and K.
      ornithinolytica had a higher motility after cultivation in KM compared with MM,
      the motility of K. terrigena was not affected. The lipolytic activity of all
      tested strains was highest after growth in MSI and PP. The composition of culture
      medium affected bacterial parameters tested to a different extent depending on
      the species.

PMID- 12184189
TI  - [Detection of the production of intracellular cytokines by T lymphocytes using
      flow cytometry--methodologic problems].
AB  - The method of assessment of intracellular proteins by means of flow cytometry
      makes it possible to evaluate the production of different cytokines by a clearly
      defined cell (sub-population type, state of cell activation). If the method
      should become a routine functional test, it must be standardized. This was the
      objective of our work when, based on data in the literature, we detected all
      controversial points and investigated them experimentally. Quite unequivocally we
      can recommend only sodium heparin as an anticoagulation agent when examining
      whole blood. The paper solves problems regarding the selection of mitogens where
      the marked effect of the use of mitogens on the result and necessity to compare
      results obtained under equal conditions was demonstrated. The authors tested also
      the possibility of preserving blood before processing and the selection of
      suitable combinations of surface signs and cytokines. When seeking the optimal
      time for cultivation it is necessary to make a compromise between the maximum
      possible production of cytokines (the kinetics of production of different
      cytokines is moreover different) and the accuracy of measurement because
      detection of the CD4 molecule after a prolonged period of stimulation
      deteriorates. As the optimum the authors recommend 4.5 hour cultivation with
      phorbol myristate acetate. The results proved a much greater capacity to retain
      newly formed cytokines in the cell if brefeldin A is used instead of monensine.
      The outcome of the work is a standard protocol for assessment of intracellular
      cytokines.

PMID- 12184190
TI  - [Septic conditions caused by yeasts and their diagnosis].
AB  - The authors present a review of factors making possible the penetration of yeasts
      into the blood stream, development of Candinaemia and sepsis, and a group of
      tests which have been used for the diagnosis of sepsis evoked by Cryptococcus
      neoformans, Candida albicans, C. glabrata, C. melinii and C. krusei.

PMID- 12184191
TI  - [Diagnostic value of determination of autoantibodies in gluten-sensitive
      enteropathy].
AB  - The study is focused on the immunopathological mechanisms of development of
      gluten-sensitive enteropathy (coeliac disease). It describes environmental
      factors and the role of autoantibodies and autoaggressive cells in the bowel
      inflammation. Attention is paid to the autoantibodies used in routine laboratory
      diagnosis of coeliac disease. The objective is a summary of rational diagnostic
      algorithms used in screening, diagnostics, treatment and dispensary care of
      patients with coeliac disease, especially with latent forms associated with other
      organ-specific immunopathological diseases. Exploration of anti-gliadin and anti
      endomysial antibodies in diabetes mellitus type I were submitted. Furthermore,
      indications of these tests in the routine laboratory practice was analyzed.

PMID- 12184192
TI  - [Resistance of microscopic fungi to selected antimycotics].
AB  - The author attended to enquiries of developing resistance of microscopic fungi
      (yeasts, micromycetes) to antimycotics used in therapy and their mechanisms of
      action.

PMID- 12184193
TI  - [Diagnosis of rotavirus infections--comparison of various methods].
AB  - In 179 samples of faeces from patients hospitalized with diarrhoeal diseases
      rotavirus infections were examined concurrently by three different sets--the
      latex agglutination test Diarlex Rota-Adeno (Orion Diagnostica) and two
      immunoenzyme tests (EIA)--EIA Rotavirus (Test-Line, CR) and IDEIA Rotavirus (Dako
      Ltd.) By the latex agglutination reaction the rotavirus infection was proved 31
      times (17.3%), by the Test-Line test 87 times (48.6%), by the Dako test 96 times
      (53.6%). During the interval of 0-3 days after the onset of the disease the
      positivity assessed by different tests was 22.8%, 48.6% and 54.3%, on the 4th-7th
      day 12.8%, 51.1% and 57.4%, on the 8th and subsequent days 3.7%, 44.4% and 44.4%.
      Comparison of sets Orion Diagnostica and Dako revealed the sensitivity of the
      latex agglutination test only as 30.2% and specificity 97.6%. After the 9th day
      from the onset of the disease the infection was no longer confirmed by the latex
      agglutination test, while both EIA tests proved the rotavirus antigen up to the
      16th day from the onset of the disease.

PMID- 12184194
TI  - [Diphtheria--results of an immunologic survey].
AB  - The objective of the immunological survey (IS) was in addition to assessment of
      the overall immunity of the Slovak population against diphtheria to test the
      effectiveness of vaccination and suitability of the used vaccination pattern and
      to assess the persistence of antibodies against diphtheria in more advanced age,
      and possibly the need of revaccination. The sera were tested by means of the
      neutralization test on cell cultures. The level of diphtheria antitoxin was
      assessed quantitatively. In the reaction standards were used--diphtheria toxin
      79/1 1000 Lf, produced in the National Institute of Public Health and the
      Environment Bilthoven, Netherlands and the diphtheria antitoxin Diphtheria
      antitoxin equine British Standard 66/153, obtained from WHO International
      Laboratory for Biological Standards, Great Britain. The overall immunity assessed
      on a nationwide scale in Slovakia was adequate (88.2%). In the child population
      the level of antibodies correlated well with the administration of individual
      vaccinations against diphtheria. In 6- to 10-year old children the serum
      positivity was as high as 100%, in older children it did not drop below 95%. A
      more marked decline of serum positivity was found in the population above 40
      years. The highest proportion of sensitive subjects was in the group of 50-59
      year-old ones (45.2%). The antidiphtheritic immunity of the population under 50
      years is very good. Inadequate immunity of adults above 50 years revealed the
      need of administering a booster dose against diphtheria which will have a
      positive impact on the antibody level of this age group of the population.

PMID- 12184195
TI  - [Amount of toothless persons is reducing--need for dental services is
      increasing].

PMID- 12184196
TI  - [Non-Hodgkin lymphomas in Southern Karelia].

PMID- 12184198
TI  - [Computer tomography in the diagnostics of gastrointestinal tract].

PMID- 12184197
TI  - [Ointment-induced local anesthesia as an anesthesia method for maxillary sinus
      puncture].

PMID- 12184199
TI  - [An acute vesicular skin disease].

PMID- 12184200
TI  - [Duodecim ambulances in the East Karelian war in 1921-2].

PMID- 12184201
TI  - [Stefan Bremer: A half-moon].

PMID- 12184202
TI  - [Even other disease processes than osteoporosis can affect the bones].

PMID- 12184203
TI  - [Parathyroid hormone--a good servant, but a bad master].

PMID- 12184204
TI  - [From the rickets in children to the osteomalacia in adults].

PMID- 12184205
TI  - [Renal osteodystrophy--more than a mere bone disease].

PMID- 12184206
TI  - [The mysterious Paget's disease].

PMID- 12184207
TI  - [Osteogenesis imperfecta--a congenital brittleness of bones].

PMID- 12184208
TI  - [Bone tumors].

PMID- 12184209
TI  - [Osteomyelitis--what old, what new?].

PMID- 12184210
TI  - The putative roles of adenosine in insulin- and exercise-mediated regulation of
      glucose transport and glycogen metabolism in skeletal muscle.
AB  - Skeletal muscle is the primary site of whole-body glucose disposal and is vital
      in determining the overall insulin sensitivity and carbohydrate management.
      Insulin and physical exercise are important stimuli for muscle glucose transport
      and glycogen metabolism. While it is known that both insulin and contraction
      stimulate muscle glucose uptake and glycogen metabolism, the post-receptor
      mechanisms are not completely understood. Local metabolic factors, such as
      adenosine, have been suggested to play a role in insulin and contraction
      regulation of carbohydrate metabolism in skeletal muscle. While adenosine has
      clearly been shown to potentiate insulin-stimulated glucose transport in
      adipocytes and heart muscle, its role in carbohydrate metabolism in skeletal
      muscle is less clear, with numerous diverging findings published to date. This
      review article summarizes findings on the putative roles of adenosine in insulin
      and exercise-mediated regulation of carbohydrate metabolism and the signalling
      pathways proposed to be central to these metabolic stimuli in skeletal muscle.

PMID- 12184211
TI  - The role of endodontics in the treatment of luxated permanent teeth.
AB  - Pulp necrosis is a common complication following traumatic dental injuries and is
      related to the type and severity of the injury, as well as to the stage of
      development of the injured tooth. Endodontic intervention is required when there
      are clinical and radiographic signs of pulpal infection and its sequelae.
      Arrested tooth development with periradicular pathosis, external inflammatory
      root resorption, sinus tract formation and pain on percussion are indicative of
      root-canal infection in the post-traumatized teeth, and require immediate
      endodontic treatment. The use of calcium hydroxide in the treatment of teeth with
      post-traumatic pulp necrosis and its sequelae has been shown to be extremely
      beneficial for the long-term retention of the injured teeth. Calcium hydroxide
      has been shown to arrest and repair external inflammatory root resorptive
      defects, eliminate the endodontopathic microorganisms from the root canal system
      and induce hard-tissue barrier formation at the apex of non-vital immature teeth.
      This paper reviews the endodontic treatment required by post-traumatic non-vital
      permanent teeth.

PMID- 12184212
TI  - Healing and prognosis of teeth with intra-alveolar fractures involving the
      cervical part of the root.
AB  - Healing and long-term prognosis of 94 cervical root fractures were evaluated. The
      teeth were divided into two groups according to type of fracture: transverse
      fractures limited to the cervical third of the root (51 incisors) and oblique
      fractures involving both the cervical and middle parts of the root (43 incisors).
      Neither the frequency nor the type of fracture healing differed significantly
      between the two groups. In the material as a whole, healing of the fracture with
      hard tissue formation was observed in 17 teeth (18%), and healing with
      interposition of periodontal ligament (PDL) and, in some cases, hard tissue
      between the fragments in 62 teeth (66%). Fifteen teeth (16%) showed no healing
      and a radiolucency adjacent to the fracture. Statistical analyses revealed that
      incomplete root formation and a positive sensibility test at the time of injury
      were significantly related to both healing and hard tissue repair. The same
      applied to concussion or subluxation compared with dislocation of coronal
      fragment, as well as optimal compared with suboptimal reposition of displaced
      coronal fragments. The type and duration of splinting (or no splinting) appeared
      to be of no significance for frequency or type of healing of cervical root
      fractures. During the observation time (mean = 75 months), 19 (44%) of the teeth
      with transverse fractures and 3 (8%) of those with oblique fractures were lost
      after healing. In conclusion, fractures in the cervical part of the root had a
      healing potential and the predictive parameters identified for fractures in other
      parts of the root seemed to be valid for the healing of cervical root fractures.
      Transverse fractures appeared to have a significantly poorer long-term prognosis
      compared to oblique fractures, apparently due to a marked post-treatment
      mobility, which often led to new luxation caused by even minor impacts.

PMID- 12184213
TI  - Fractured teeth bonded with dentin adhesives with and without unfilled resin.
AB  - Fractured incisors were restored by reattaching the fragment to the remaining
      tooth structure. For this purpose, seven dentin adhesive systems were used with
      and without an unfilled resin (Heliobond) and the strength of the restored teeth
      was tested at a cross-head speed of either 1 or 500 mm/min. The hypothesis was
      that the strength of the reattachment would be higher when an unfilled resin was
      used. The dentin adhesive systems were Prime & Bond NT (PB), Excite (EX), One
      Step (OS), PQ1 (PQ), SingleBond (SB), Optibond Solo Plus (OS), and an
      experimental adhesive (GL). Statistical analysis revealed that with all adhesives
      except EX, a significantly greater mean fracture strength was achieved when the
      adhesives were used with the resin (Heliobond). Furthermore, with all adhesives
      except PB, there was a significantly lower mean fracture strength when tested at
      500 mm/min than at 1 mm/min. All the tested adhesives except EX should be used
      with an unfilled resin when restoring fractured teeth by reattachment.

PMID- 12184214
TI  - Reinforcing effect of a resin glass ionomer in the restoration of immature roots
      in vitro.
AB  - Fifty-six extracted maxillary central incisors were used for this study. The
      crown of each tooth was removed in order to obtain a standard length of 13 mm.
      Root canals were enlarged to simulate immature teeth after apexification. The
      apical 2 mm of the root canal was obturated with gutta-percha and AH26 sealer.
      The specimens were divided into two groups. Group A was unrestored and served as
      positive control. In group B, the canal walls were reinforced with a resin
      modified glass ionomer using a translucent curing post. All teeth were subjected
      to compressive force using an Instron testing machine until fracture occurred.
      Group B showed an increased resistance to fracture (456.02 +/- 172.47 N) compared
      with group A (263.46 +/- 98.00 N). The difference between groups was
      statistically significant (P < 0.005).

PMID- 12184215
TI  - Factors affecting resorption in traumatically intruded permanent incisors in
      children.
AB  - There is a lack of consensus concerning the management of intruded permanent
      teeth. The objectives of the present study were to determine the prevalence of
      resorption for intruded permanent teeth and to establish the effect of factors on
      the timing, prevalence and rate of resorption and to examine the relationship
      between the timing of onset and the subsequent rate of resorption. Sixty-one
      intruded permanent incisors treated at the Paediatric Dentistry units in Belfast
      and Newcastle upon Tyne, during the period 1990-99 with a minimum follow-up
      period of 1.5 years, were studied. The timing and presence of resorption and its
      rate of occurrence over time were set as the principal outcomes. There was a
      significantly earlier onset and higher prevalence of resorption in more severely
      intruded teeth (P< 0.05). There was also a significant relationship between the
      degree of apical development and resorption with an increased prevalence in the
      more fully developed roots (P< 0.001). Resorption was detected significantly
      earlier in teeth with higher rates of resorption (P< 0.05). However, the
      treatment method did not significantly affect the prevalence or rate of
      resorption. In conclusion, the occurrence of root resorption after intrusive
      trauma appears to be related to the severity of the original injury and the stage
      of root development rather than the repositioning procedure.

PMID- 12184216
TI  - Clinical and epidemiological study of traumatic root fractures.
AB  - The aim of this work was to study the prevalence and clinical presentation of
      root fractures in a series of patients with dental trauma. Treatment strategies
      were classified and outcomes after a 6-month period presented. The study
      population comprised 76 patients (between the ages of 2 and 55 years) with 93
      root fractures in their teeth (18 primary, 75 permanent). Data were collected
      following the taking of a detailed clinical history, objective clinical
      examination and photographic and radiological investigation. Since most of the
      primary teeth were extracted, only cases with root fracture of permanent teeth
      were followed-up: in all, 24 patients with 31 teeth with root fractures. The
      prevalence of root fractures in permanent teeth was 7.7% of all injuries, while
      in primary teeth it was 3.8%. The most frequently involved teeth were the
      maxillary incisors with a percentage of 75% in permanent teeth. Moreover, 40% of
      root fractures in permanent teeth were associated with fracture of the alveolar
      bone and of the soft tissues and in 45% of cases, the adjacent teeth were also
      injured. The results of this study reaffirm the necessity for scrupulous
      diagnosis of teeth after a traumatic injury. Adjacent teeth and those in the
      opposing arch should not be ignored. Treatment is multidisciplinary, requiring
      surgical, orthodontic, operative and prosthetic compliance. Periodic check-up is
      essential.

PMID- 12184217
TI  - Use of a removable splint in the treatment of subluxated, luxated and root
      fractured anterior permanent teeth in children.
AB  - AIM: The aim of this study was to evaluate the prognosis of subluxated, luxated
      and root fractured teeth in children treated by removable splints, designed to
      stabilize mobile anterior teeth and eliminate occlusal trauma due to
      malocclusion. MATERIAL AND METHODS: A total of 227 traumatized anterior teeth (91
      subluxated, 105 luxated and 31 root fractured teeth) treated with a removable
      splint were observed for 3 years. The traumatized teeth were from 79 children
      aged between 6-12 years (mean 8 years 5 months). If a traumatized tooth was
      extremely mobile, a fixed splint was first made before the impression was taken
      for the removable splint. Two weeks after completion of the removable splint
      treatment, an impression was taken again to evaluate the occlusal relationship of
      pre- versus post-treatment of removable splint. RESULTS: The treatment period
      with a removable splint averaged 3 weeks in subluxated teeth, 3-5 weeks in
      luxated teeth, 4-6 weeks in apical third root fracture injuries, and more than 5
      weeks in middle third root fracture injuries. All the subluxated teeth and 74.1%
      of the luxated teeth maintained their pulp vitality during the 3-year follow-up
      period. Two of 21 (9.5%) apical third root fracture teeth and three of five (60%)
      middle third root fracture teeth had pulp necrosis in the coronal fragments.
      Internal resorption was not found in any of the traumatized teeth. External
      replacement resorption was not found in subluxated and luxated teeth. All the
      root fractured teeth displayed transient external resorption around the fracture
      lines. The surface resorption appeared to be self-limiting and not to threaten
      the retention of the tooth. Inflammatory resorption was observed in teeth with
      pulp necrosis, but in all cases this was reversed with endodontic treatment.
      Eight of 23 (39%) apical third root fractured teeth displayed replacement
      resorption in their apical fragments, but the resorption was not serious enough
      to extract the tooth. No obvious alteration in the occlusal relationship was
      found comparing pre- and post-treatment casts. The removable splints appeared to
      positively affect healing after traumatic injuries, as evidenced by the low
      number of complications at the 3-year follow-up period.

PMID- 12184218
TI  - A two-probe laser Doppler flowmetry assessment as an exclusive diagnostic device
      in a long-term follow-up of traumatised teeth: a case report.
AB  - The reliability of laser Doppler flowmetry in a two-probe assessment of pulpal
      blood flow is well known. The purpose of this case report was to determine its
      use as an exclusive and reliable tool for tooth vitality diagnosis in a long-term
      follow-up. As a result of a traumatic injury to a 24-year-old Caucasian female,
      tooth pulp vitality was studied in six maxillary front teeth over 30 weeks using
      two-probe laser Doppler flowmetry and current sensitivity tests. A similar
      assessment was repeated after 228 weeks. Confronted with an alveolar bone
      fracture with a tooth in the fracture line, one intrusion and several luxated
      teeth, current sensitivity tests are found not to be as reliable indicators of
      revascularisation, as significant results are obtained later (7 weeks) than using
      laser Doppler flowmetry tests (1 week). A pathway with ischaemia (3 weeks),
      hyperaemia (7 weeks) and restored blood supply in the pulp measured by laser
      Doppler flowmetry tests was found and avoided endodontic treatment. Teeth
      vascularisation evolved normally (228 weeks). Despite a strong indication in all
      sensitivity tests for endodontic treatment, the use of laser Doppler flowmetry
      tests was clear, more reliable than sensitivity tests and exclusive, as
      denervation was postponed and pulp vascularisation evident.

PMID- 12184219
TI  - Survival of intentionally retained permanent incisor roots following crown root
      fractures in children.
AB  - Retaining tooth roots, following crown loss, confers a number of benefits
      including the preservation of alveolar bone. Intentional root retention in adults
      has been widely investigated but little is known about this treatment approach in
      children. Therefore, the aim of the present study was to investigate the clinical
      outcomes associated with permanent anterior root retention in a young population.
      The study group comprised 53 children who had received treatment in the
      paediatric dentistry clinic, Charles Clifford Dental Hospital, Sheffield, UK,
      over the past 10 years, following a complicated crown root fracture of a
      permanent maxillary incisor at or below the gingival margin. Data relating to
      patient age at crown root fracture, gender, previous trauma history, tooth
      vitality, treatments performed and clinical outcomes were obtained
      retrospectively using patient records. The mean age of the subjects at initial
      crown root fracture was 12.1 years (range 8.3-15.8 years) and there were more
      than twice as many males (n = 37, 70%) as females (n = 16, 30%). In just over
      half of the cases seen (n = 29, 54%), the tooth involved was already nonvital at
      the time of crown root fracture. For the majority of these nonvital teeth (n =
      27, 93%), primary treatment had comprised placement/replacement of a calcium
      hydroxide root dressing. The remaining two teeth did not require root treatment
      as a satisfactory gutta percha root filling was already present. A variety of
      treatments was undertaken for the 24 vital roots: in 15 (63%) cases the pulp was
      extirpated and calcium hydroxide placed; three (12%) cases were subject to a
      pulpotomy; five (21%) cases were left untreated with the hope that vitality would
      be maintained following gingival healing and in one case the radicular pulp was
      extirpated and immediately obturated with gutta percha. The mean time that the
      roots were kept under review was 2.6 years (+/- 1.57, range 0.6-6.8). During this
      period, only five roots (9%) had to be removed due to persistent periapical
      infection. There were no complications associated with the five cases where vital
      root submergence had been permitted but all three cases which had initially
      undergone a pulpotomy subsequently presented with pulpal necrosis necessitating
      pulpal extirpation and calcium hydroxide therapy. These findings indicate that
      efforts to retain permanent anterior roots in a young population are justified in
      view of the high clinical success rate of over 90% over a 2-year period.

PMID- 12184220
TI  - Repair characteristics of horizontal root fracture: a case report.
AB  - Radicular fractures in permanent teeth are uncommon injuries among dental
      traumas, comprising 0.5-7% of the cases. Fracture occurs most often in the middle
      third of the root and rarely at the apical-third. The present paper reports a
      clinical case of a horizontal radicular fracture located between the middle- and
      apical-third of a upper left-central incisor followed-up for over 3 years. The
      tooth was extracted owing to periodontal reasons. Histomorphologically, it showed
      pulp-vitality preservation and root healing by hard-tissue deposition.

PMID- 12184221
TI  - The Euler number as an index of spatial integrity of landscapes: evaluation and
      proposed improvement.
AB  - The spatial integrity of a habitat or landscape is determined by the occurrence
      of habitat fragments and of perforations inside them. A landscape is said to have
      less spatial integrity with increasing numbers of fragments and perforations. The
      Euler number (epsilon) is a numerical measure of spatial integrity, based upon
      the difference (nf-np) between the number of fragments (nf) and the number of
      perforations (np). In this contribution, epsilon is evaluated, and an improvement
      is presented as a new index epsilon*, which is a combination of two metrics
      (epsilon j, epsilon d) based on nf and np. The term epsilon j quantifies the
      intensity of perforation and/or fragmentation. The term epsilon d measures the
      extent to which fragmentation predominates perforation, and vice versa. The
      intensity and dominance measures are combined into an Euclidean distance measure,
      generating the new ensemble value epsilon*, calculated as epsilon* = (nf + np)-1
      square root of [1 + nf2]. Use, sensitivity, and application of epsilon*, epsilon
      j, and epsilon d are illustrated using percolation maps. Application of the new
      metrics by environmental scientists is encouraged because (1) no negative values
      can be generated with epsilon*, epsilon j, and epsilon d; (2) the range of
      epsilon*, epsilon j, and epsilon d is fixed; (3) process dominance and intensity
      are both assessed; (4) epsilon*, epsilon j, and epsilon d are easy to calculate
      and to interpret; and (5) epsilon* is not only based upon (nf - np), as epsilon
      is. Guidelines for practical use by means of a biplot of epsilon j and epsilon d
      are given.

PMID- 12184222
TI  - Acute hypoxemia does not increase the oxidative stress in resting and contracting
      muscle in humans.
AB  - In healthy humans sustaining static handgrip at 60% of maximal voluntary
      contraction (MVC) until exhaustion, we measured the venous blood concentration of
      reduced ascorbic acid (RAA) and thiobarbituric acid reactive substances (TBARS),
      respectively, used as markers of the post-exercise oxidative stress and lipid
      peroxidation. Measurements were conducted in normoxemia, then during a 30-min
      period of hypoxemia (PaO2 = 56 mmHg) produced by inhalation of an hypoxic gas
      mixture. Compared to normoxemia, hypoxemia did not significantly modify the
      resting concentrations of TBARS and RAA, and did not affect the consumption of
      ascorbic acid after 60% MVC but suppressed the post-exercise TBARS increase. We
      conclude that acute hypoxemia does not modify the production of oxygen free
      radicals after strenuous static efforts and even seems to attenuate the lipid
      peroxidation.

PMID- 12184223
TI  - Trying to promote EBP in your school of nursing? Don't overlook non-nursing
      students.

PMID- 12184224
TI  - Report on new drugs.

PMID- 12184225
TI  - Women's issues--updates from the 7th CROI.

PMID- 12184226
TI  - Complications of HIV therapy.

PMID- 12184228
TI  - Hepatitis C emerging.

PMID- 12184227
TI  - Update on opportunistic infections.

PMID- 12184229
TI  - Pharmacology and drug interactions: compartmentalizing antiretrovirals.

PMID- 12184230
TI  - Viral load, circumcision and heterosexual transmission.

PMID- 12184231
TI  - Report from the 7th CROI (San Francisco, February 2000): genital tract HIV.

PMID- 12184232
TI  - Report from the 7th CROI (San Francisco, February 2000): update on neurological
      manifestations of HIV infection.

PMID- 12184233
TI  - When will once (-a day) be enough?

PMID- 12184234
TI  - New guidelines for antiretroviral therapy from the IAS--USA and DHHS.

PMID- 12184235
TI  - Public health service task force updates recommendations for use of
      antiretroviral drugs in pregnant women.

PMID- 12184236
TI  - The world AIDS conference in Durban, South Africa--science, politics, and health.

PMID- 12184237
TI  - Opportunistic infections.

PMID- 12184238
TI  - Morphologic and metabolic changes associated with HIV therapy.

PMID- 12184239
TI  - Snapshot from Durban: new antiretroviral agents.

PMID- 12184241
TI  - Drug interactions and pharmacology.

PMID- 12184240
TI  - Antiretroviral therapy.

PMID- 12184242
TI  - Snapshot from Durban: initiation of antiretroviral therapy.

PMID- 12184244
TI  - Report from the 38th IDSA: preserving the immune response to HIV, HAART, and long
      term toxicities.

PMID- 12184243
TI  - HIV-1 infection in women.

PMID- 12184245
TI  - Update on complications of HAART from ICAAC and the 2nd International Workshop on
      Adverse Drug Reactions and Lipodystrophy in HIV.

PMID- 12184246
TI  - Report from the 38th IDSA: tuberculosis & HIV.

PMID- 12184247
TI  - Developments in opportunistic infections from IDSA and ICAAC 2000.

PMID- 12184248
TI  - Report from the 38th IDSA: STDs, HIV and HIV prevention.

PMID- 12184249
TI  - Report from ICAAC 2000: HIV & viral co-infections.

PMID- 12184251
TI  - What's new with IL-2?

PMID- 12184250
TI  - Antiretroviral news from ICAAC 2000.

PMID- 12184252
TI  - Structured therapeutic interruptions: a review.

PMID- 12184253
TI  - HIV-associated lymphomas: the last opportunists?

PMID- 12184254
TI  - New drugs.

PMID- 12184256
TI  - Is the chance to cut a chance to cure? The cesarean section controversy
      revisited.

PMID- 12184255
TI  - The global HIV pandemic: lessons from the past and glimpses into the future.

PMID- 12184257
TI  - When should highly active antiretroviral therapy be initiated?

PMID- 12184258
TI  - New guidelines for the use of antiretroviral agents in HIV-infected adults and
      adolescents.

PMID- 12184259
TI  - Drug transporter, drug concentrations, and drug interactions.

PMID- 12184260
TI  - Adherence to antiretroviral therapy.

PMID- 12184261
TI  - New antiretroviral agents.

PMID- 12184262
TI  - Antiretroviral therapy: naive patients and early therapy.

PMID- 12184263
TI  - Report from the 8th CROI: women's issues.

PMID- 12184264
TI  - Hepatitis C coinfection gains a foothold at the 8th CROI.

PMID- 12184265
TI  - Treatment of antiretroviral-experienced patients: new data from the 8th CROI.

PMID- 12184266
TI  - cDNA sequence of porcine thioredoxin.
AB  - Several mammalian thioredoxin cDNA sequences, namely that of human, macaca,
      ovine, bovine, equine and murine have been already registered in the Genbank
      database; but that of porcine is still not known. In this communication, we
      report the full-length cDNA sequence of porcine thioredoxin as determined by RT
      PCR method. We also compared the protein sequence of thioredoxin from various
      mammals. Multialignment of the amino acid sequences between porcine and other
      mammalian species revealed that the sequences are highly conserved. Only one
      difference exists between the amino acid sequences of porcine and bovine
      thioredoxin.

PMID- 12184267
TI  - My brilliant career--human resources. Escalating skills.

PMID- 12184268
TI  - Nursing practice guideline. 6. Confidentiality. 7. Duty to provide care.

PMID- 12184270
TI  - Patients with mitral regurgitation, a more accurate estimate of PCWP.

PMID- 12184269
TI  - The principle of multidimensional arrays.
AB  - Echocardiography is one of the most important diagnostic tools in cardiology
      today. One-dimensional phased arrays have been used extensively because they have
      a small footprint and allow beam steering. Their major limitation lies in that
      these devices can only be used to acquire images of two-dimensional slices in
      real-time and that the slice thickness cannot be controlled. To allow real-time
      three-dimensional imaging of the heart and focusing of the ultrasonic beam in two
      dimensional, two-dimensional arrays, the design and fabrication of which are
      enormous engineering challenges, are required. Before reaching this ultimate
      goal, limited focusing in the elevational plane can be achieved with 1.5
      dimensional arrays. Focusing in the elevational plane allows a reduction in slice
      thickness and thus an improvement in the image quality over a larger depth of
      view.

PMID- 12184271
TI  - Big chill in fridge recycling.

PMID- 12184272
TI  - Reflections on the first anniversary of N. Catsimpoolas' death.

PMID- 12184273
TI  - Nonmyeloablative transplantation challenged by experimentation.

PMID- 12184274
TI  - Gene expression profiling of the functionally distinct human bone marrow stromal
      cell lines HS-5 and HS-27a.

PMID- 12184275
TI  - Acidic and neutral sialidase in the erythrocytes of patients with Type 2
      diabetes: influence on erythrocyte lifespan.

PMID- 12184276
TI  - Expression of Ikaros isoforms in patients with acute myeloid leukemia.

PMID- 12184277
TI  - Frequency of BCL-2/J(H) translocation in healthy males exposed to low-level
      radiation in comparison to age-matched health controls.

PMID- 12184278
TI  - Second malignancy after treatment of acute promyelocytic leukemia: experience of
      GIMEMA trials. Gruppo Italiano Malattie Ematologiche dell'Adulto.

PMID- 12184279
TI  - Oxidation of glutathione peroxidase-deficient red cells by organic peroxides.

PMID- 12184280
TI  - Long-term treatment with sildenafil in a thalassemic patient with pulmonary
      hypertension.

PMID- 12184281
TI  - AML, angiogenesis, and prognostic variables.

PMID- 12184282
TI  - SENV-H viremia and liver transplantation: significant increase of the prevalence.

PMID- 12184283
TI  - Efficacy of a low dose of thalidomide in advanced multiple myeloma.

PMID- 12184284
TI  - EKG "SOS" may help doctors decide when to implant life-extending ICDs.

PMID- 12184285
TI  - Heart attack patients take a trip for angioplasty.

PMID- 12184286
TI  - Mental stress constricts vessels, raising cardiac risk.

PMID- 12184288
TI  - The heart-healthy diet. No-fat foods can make you fat. To beat obesity, watch
      calories, add fiber, and exercise more.

PMID- 12184287
TI  - New marker for vessel inflammation--and another reason to exercise.

PMID- 12184289
TI  - Be WWWary of Internet drugs.

PMID- 12184290
TI  - "Peace-of-mind" health proxies.

PMID- 12184291
TI  - Ask Dr. Francis. I recently had a stroke and was told that the only possible
      cause the doctors could find was plaque protruding into my aorta. What can be
      done about this?

PMID- 12184292
TI  - Ask Dr. Francis. I just had a cardiac catheterization for chest pain. My
      cardiologist said he saw a 50 percent narrowing in one of the arteries. I was
      surprised when he didn't perform an angioplasty but instead just recommended some
      medications. Why not stent the 50 percent blockage?

PMID- 12184293
TI  - Ask Dr. Francis. A catheterization revealed a severe narrowing in one of my
      coronary arteries. My cardiologist recommended that I return for an angioplasty
      and stent procedure. Should I wait until coated stents are available?

PMID- 12184294
TI  - Challenges to female condom integration into condom programming.

PMID- 12184295
TI  - [Heterosis of quantitative trait loci modifying lifespan in Drosophila
      melanogaster].
AB  - Knowledge of genes responsible for aging and death is a prerequisite for
      determining the relative contributions of the different evolutionary factors
      responsible for the limited duration of life. Polymorphism of these genes
      probably accounts for the variation in lifespan. Previously, quantitative trait
      loci (QTLs) controlling this variation were mapped with the use of 98 recombinant
      inbred (RI) lines originating from two parental isogenic Drosophila melanogaster
      stocks. In each RI line, lifespan was measured for 25 males and 25 females, and
      alleles were established for 93 marker genes segregating between the parental
      lines. Significant correlation between marker segregation and lifespan was
      revealed for several chromosome regions. The lifespan genes had sex-specific
      effects and late age onset. In the present work, the effects of the QTLs were
      compared for homozygous and heterozygous flies. In Six out of the eight detected
      QTLs alleles that decreased lifespan were recessive. Heterosis was observed for a
      of QTL at 33E-38A. Thus, heterosis might contribute to maintaining variation in
      lifespan in natural populations.

PMID- 12184296
TI  - Botox cosmetic: a look at looking good.

PMID- 12184297
TI  - Bottled water: better than the tap?

PMID- 12184298
TI  - The FDA's drug review process: ensuring drugs are safe and effective.

PMID- 12184299
TI  - 'Six-pack abs' electronically?

PMID- 12184300
TI  - What to look for in a pair of sunglasses.

PMID- 12184301
TI  - Battle of the bugs: fighting antibiotic resistance.

PMID- 12184302
TI  - New use approved for Vioxx.

PMID- 12184303
TI  - New OTC drug facts label.

PMID- 12184304
TI  - Florida couple admits using phony treatment to attract clients.

PMID- 12184305
TI  - Home dialysis system.

PMID- 12184306
TI  - FDA approves restricted marketing of Lotronex.

PMID- 12184308
TI  - Blood transfusions may cause lung damage.

PMID- 12184307
TI  - We can't forget the value of vaccines.

PMID- 12184309
TI  - Firm signs consent decree prohibiting ephedrine products.

PMID- 12184310
TI  - FDA warns sellers of nicotine lollipops, lip balm.

PMID- 12184311
TI  - New treatment for advanced breast cancer.

PMID- 12184312
TI  - New type of defibrillator.

PMID- 12184313
TI  - First synthetic secretin.

PMID- 12184314
TI  - First vaccine for cat AIDS approved for veterinary use.

PMID- 12184316
TI  - Disease modifying therapies in multiple sclerosis.

PMID- 12184315
TI  - 100 years of biologics regulation.

PMID- 12184317
TI  - Reversible ALS-like disorder in HIV infection. An ALS-like syndrome with new HIV
      infection and complete response to antiretroviral therapy.

PMID- 12184318
TI  - [Mechanisms of radio-induced apoptosis].
AB  - A general overview of the activation mechanisms of programmed cell death or
      apoptosis following an irradiation is given in this review. First, are summarized
      the main induction pathways of radiation-induced apoptosis by which extracellular
      (tumor necrosis factor (TNF), Fas ligand, TNF-related apoptosis-inducing ligand
      (TRAIL)) and intracellular (mitochondria and caspases) signals are integrated. A
      second part is then devoted to the importance of p53 and of its regulators (ATR,
      ATM, DNA-PKcs) in the process of radiation-induced apoptosis. Thereafter, signal
      transduction pathways and more specially the role of some protein kinases (MEKK,
      SAPK/JNK, p38-MAPK) is treated. At last, a chapter concerns the clinical interest
      of radiation-induced apoptosis and the implication of apoptosis in the treatment
      of certain diseases.

PMID- 12184319
TI  - [Molecular mechanisms of the protective effect of vitamin e against
      atherosclerosis].
AB  - Oxidation of low-density lipoproteins constitutes the first step of a very
      complex process leading to atherosclerosis. Vitamin E, and principally a
      tocopherol, is considered as the principal inhibitor of lipid peroxidation. Some
      studies showed the beneficial role of vitamin E in the prevention and reduction
      of atherosclerosis and its associated pathologies. However, other in vitro
      studies advance a prooxidant role of vitamin E. The results of the epidemiologic
      studies are difficult to generalize without taking account of the clinical
      randomized tests. In this work, we reviewed the principal studies devoted to the
      role of vitamin E and discussed the assumption of a prooxidant effect of this
      molecule.

PMID- 12184320
TI  - [The influence of age on radiation-induced cognitive deficit:experimental studies
      on brain irradiation of 30 gy in 10 sessions and 12 hours in the Wistar rat at 1
      1/2, 4 and 18 months age].
AB  - The objective of this study was to determine the influence of age on the learning
      and memory dysfunction induced by cranial radiation in the male Wistar rat.
      Ninety-six 45-day-old, 70 4-month-old, and 78 18-month-old male rats were divided
      in two equal groups: (i) irradiated and (ii) control. A course of whole-brain
      radiation therapy (30 Gy in 10 fractions over 12 days) was administered to the
      irradiated group, while the control group received sham irradiation. Sequential
      behavioral studies including one and two-way avoidance tests were undertaken
      before and after the 7 months following radiation. The results suggest that
      radiation induced progressive and irreversible memory dysfunction in elderly (18
      month-old) rats, but this effect was partial or almost reversible in the 4-month
      old and 45-day-old rats, respectively. In return, the learning dysfunction was
      age non-dependent despite the fact that is occurs more rapidly in the young (45
      days, 4 months) rats.

PMID- 12184321
TI  - [Secondary medullary aplasia from accidental radiation:therapeutic options and
      evolution of the concept].
AB  - Bone marrow grafting following accidental irradiation exposure should be viewed
      in the perspective of a severe myeloablative syndrome linked to high medullary
      damage for a dose range higher than 6-8 Gy, resulting in very late or no
      recovery. Prognosis will depend on the presence or absence of radio-combined
      injuries, the toxicity of the transplant procedure, and the risk of rejection
      induced by insufficient percritical immunosuppression. It is in this context that
      new cell therapy modalities, which combine enhanced peripheral hematopoietic cell
      engraftment and high immunosuppressive conditioning regimen with low
      extrahematological toxicity, inducing early and stable mixed lymphomyeloid
      chimerism with minimal morbidity, can be considered. Such an approach is being
      evaluated in the treatment of patients with hematological malignancies at high
      risk of transplant-related mortality using conventional bone marrow methods.

PMID- 12184322
TI  - [The effects of ionizing radiation on stem cells and hematopoietic progenitors:
      the place of apoptosis and the therapeutic potential of anti-apoptosis
      treatments].
AB  - Abstract: Bone marrow aplasia observed following ionizing radiation exposure
      (Total Body Irradiation; gamma dose range: 2-10 Gy) is a result, in particular,
      of the radiation-induced (RI) apoptosis in hematopoietic stem and progenitor
      cells (HSPC). We have previously shown in a baboon model of mobilized peripheral
      blood CD34+ cell irradiation in vitro that RI apoptosis in HSPC was an early
      event, mostly occurring within the first 24 hours, which involves the CD95 Fas
      pathway. Apoptosis may be significantly reduced with a combination of 4 cytokines
      (4F): Stem Cell Factor (SCF), FLT-3 Ligand (FL), thrombopoietin (TPO), and
      interleukin-3 (IL-3), each at 50 ng x mL(-1) (15% survival versus <3% untreated
      cells, 24 h post-irradiation at 2.5 Gy). In this study we show that addition of
      TNF-alpha(800 IU/ml) induces an increase in 4F efficacy in terms of cell survival
      24 h after incubation (26% survival after 24 h irradiation exposure at 2.5 Gy)
      and amplification (k) of CD34+ cells after 6 days in a serum free culture medium
      (SFM) (kCD34+ = 4.3 and 6.3 respectively for 4F and successive 4F + TNF-a/ 4F
      treatments). In addition, the 4F combination allows culture on pre-established
      allogenic irradiated stromal cells in vitro at 4 Gy (kCD34+ = 4.5). Overall this
      study suggests (i) the potential therapeutic interest for an early administration
      of anti-apoptotic cytokines with or without hematopoiesis inhibitors (emergency
      cytokine therapy) and (ii) the feasibility in the accidentally irradiated
      individual, of autologous cell therapy based on ex vivo expansion in order to
      perform autograft of residual HSPC collected after the accident.

PMID- 12184323
TI  - [Specific parameters for the calculation of dose after aerosol inhalation of
      transuranium elements].
AB  - A review on specific parameter measurements to calculate doses per unit of
      incorporation according to recommendations of the International Commission of
      Radiological Protection has been performed for inhaled actinide oxides. Alpha
      activity distribution of the particles can be obtained by autoradiography
      analysis using aerosol sampling filters at the work places. This allows us to
      characterize granulometric parameters of "pure" actinide oxides, but
      complementary analysis by scanning electron microscopy is needed for complex
      aerosols. Dissolution parameters with their standard deviation are obtained after
      rat inhalation exposure, taking into account both mechanical lung clearance and
      actinide transfer to the blood estimated from bone retention. In vitro
      experiments suggest that the slow dissolution rate might decrease as a function
      of time following exposure. Dose calculation software packages have been
      developed to take into account granulometry and dissolution parameters as well as
      specific physiological parameters of exposed individuals. In the case of poorly
      soluble actinide oxides, granulometry and physiology appear as the main
      parameters controlling dose value, whereas dissolution only alters dose
      distribution. Validation of these software packages are in progress.

PMID- 12184324
TI  - [Methods to measure the cutaneous transfer of radionuclides across the intact or
      lesioned epidermis, application to radiotoxicology].
AB  - Although skin contamination by radionuclides is the most common cause of nuclear
      workers accidents, few studies dealing with the penetration of radioactive
      contamination through the skin are available. This work is a review of
      experimental methods that allow to assess transfer of radionuclides through the
      skin in occupational conditions, with or without skin trauma. The first section
      describes the different methods applied for skin transfer assessment of chemicals
      used in pharmacology. Major radionuclide contamination accidents can be
      associated with skin traumas. Thus, the second section describes the adaptation
      of these methods to radiotoxicology. Finally, the third section is an in vivo
      investigation of cobalt transfer (57CoCl2) through undamaged and damaged skin
      which simulates different industrial accident conditions (excoriation, acid or
      alcalin burn, scalding, branding).

PMID- 12184325
TI  - [The SILENE reactor: a tool adapted for applied study of moderate and large
      doses].
AB  - Designed in 1974 to study the phenomenology and consequences of a critical
      accident, the SILENE experimental reactor, an intense source of mixed neutron and
      gamma radiation, is also suited to radiobiological studies.

PMID- 12184326
TI  - Anti-CD154 monoclonal antibody and thromboembolism revisted.

PMID- 12184327
TI  - ["Doghearted" women: the origins of the counting method].
AB  - The so called counting-method of contraception was widely used even by the
      Greeks, though its scientific explanation has been elaborated only in the 1930s
      by Knaus and Ogino. The Greeks however misunderstood the process of conception
      and did not follow the periods of humans, but those of other mammals, so their
      method probably proved to be inefficient. The theory nevertheless, in spite of
      all experiences, survived for centuries and was still in use even in the 16th
      century. Author attempts to give an answer to this fact: according to her
      opinion, based on medical, historical, and literary sources, the mystery could be
      explained by the Greek concept of genders, and the identification of dogs with
      women.

PMID- 12184328
TI  - [The concept of illness in ancient Israel].
AB  - Author - analysing primarily the text of the Holy Script - presents the most
      important characteristics of the concept of illness in ancient Israel. According
      to him illnesses were described mostly by their evident symptoms - so
      identification of the different diseases remains almost impossible. On the other
      hand illnesses were regarded as punishments of sins against God or against the
      Law, so the most efficient, or the only advised remedy was the prayer and the
      repentance. This concept changed only in late Hellenic times, especially in the
      Book of Sirach (2.c.A.D.).

PMID- 12184329
TI  - [Health-care in the 1809 "insurrection" of Hungarian noblemen)].
AB  - The author, Laszlo Barany PhD (1921-1986), was an eminent researcher of military
      history. The present article-published and edited by his grandson-contains
      excerpts from his monograph "The French Wars and Hungary in 1797-1815". Hungary,
      being a part of the Hapsburg Empire certainly took part in the Napoleonic wars on
      the Kaiser's side. Hungarian troops fought all over with revolutionary French
      armies and later with those of Napoleon in various campaigns throughout the wars.
      But military operations arrived on the Hungarian border only in 1809 when a
      division of the French Army invaded Hungary and the Hungarian nobility responded
      the attack by erecting an insurrectionist army of the noblemen which had not been
      called in for more than a century. The battle took place at Gyor, not very far
      away from the Austrian borders, and the insurrectionist troops were quickly
      defeated, though the French army returned soon to Austria. The author
      concentrates on the health services of the Hungarian army, which produced an
      unexpectedly effective network. It was, prepared and organised according to the
      directives of the physician Ferenc Eckstein, professor of the University of Pest.
      The author based on interesting archival data reconstructs the medical history of
      this short war-including its financial aspects as well.

PMID- 12184330
TI  - [My professional biography and bibliography].
AB  - I. Csapody was ophthalmologist, professor of eye surgery, Academic Doctor of
      Medical Sciences. He was born in Budapest in 1892, finished his studies in
      Budapest, had been at the front for years during World War I. As a young man he
      became Head of Department of Ophthalmology and worked in several institutes,
      later in St. John's Hospital for 30 years. In his well-organized institute of
      high level many specialists had been trained. In 1929 he published his procedure
      to make individual contact glasses with moulding of living eye. However, he was
      not concerned with industrial relations of his invention. His method was taken
      over by Zeiss Works and, in London Mr. Dallos based manufacturing on that. His
      operation for reconstruction of contracted orbital cavity due to an accident or
      chemical inquiry, making possible wearing ocular-prothese with use of free skin
      graft, can be found in great monographs on surgery, too: Arruga, Blaskovics,
      Thiel, Mackensen- Neubauer. His book entitled "Latas-probak" (Test Types for Near
      and Test Tables for Distant) was revised and published in three successive
      editions. Among his other publications in Hungarian and world-wide languages
      there are 7 books, 14 chapters in other books and approx. 160 papers. He retired
      in 1960 and died in 1970.

PMID- 12184331
TI  - [The history of the first Jewish hospitals in Pest].
AB  - Author tells the story of the first Jewish hospitals in Pest (Budapest). The
      first Jewish hospitals were founded at the end of the XVIIIth century. In 1808
      the permanently growing community hired a building for the hospital. Its first
      director was Fulop Jakubovics. Since the building soon proved to be narrow, the
      Jewish community decided to get hold of an own house. After some delay caused by
      the lack of money and the bureaucratic leadership of the town, the hospital
      opened its gates in 1840, in the presence of the Palatine of Hungary, Joseph
      Hapsburg. The staff of the new hospital consisted of eminent physicians of the
      era: Fulop Grosz, Bertalan Stiller, Gyula Boke, Adolf Hermann, Adolf Szili etc.
      In 1889 a new modern hospital was build in the Gyar (today Szabolcs) Street: At
      the beginning of the 20th century this hospital belonged to the most developed
      and most effective health institutions of the region. In the fifties the hospital
      was "socialized": nowadays the Faculty of Health-Sciences of the Semmelweis
      University is to be found in its building.

PMID- 12184332
TI  - Emergency medicine. Changes to algorithm were not approved by Resuscitation
      Council (UK).

PMID- 12184333
TI  - Emergency medicine. Ambulatory alternatives exist.

PMID- 12184334
TI  - Grading referrals to specialist breast units. Communication has been degraded to
      exchange of dataset.

PMID- 12184335
TI  - General perception of stroke. Poor knowledge of stroke can be improved by simple
      measures.

PMID- 12184336
TI  - Licensing system for doctors. Accumulating points has not changed the way I
      learn.

PMID- 12184338
TI  - Getting the best out of RITA.

PMID- 12184337
TI  - Towards higher specialist training.

PMID- 12184339
TI  - David Burckett-St Laurent.

PMID- 12184340
TI  - National competition ratios should be available for all HST applicants.

PMID- 12184341
TI  - Taking study leave.

PMID- 12184342
TI  - Multicultural factors for international spaceflight.
AB  - Spaceflight operations, including the International Space Station (ISS) and a
      mission to Mars, depend on international cooperation. Accordingly, safety,
      performance, and mission success rely on how well crews and operational personnel
      with different cultural backgrounds operate together. This paper outlines 10
      areas related to spaceflight that are influenced by the national culture and
      backgrounds of personnel: (a) Communication, (b) Cognition and Decision Making,
      (c) Technology Interfacing, (d) Interpersonal Interactions, (e) Work, Management,
      and Leadership Style, (f) Personal Hygiene and Clothing, (g) Food Preparation and
      Meals, (h) Religion and Holidays, (i) Recreation, and (j) Habitat Aesthetics.
      Research findings and recommendations are presented, as well as a multicultural
      training approach to reduce potential challenges for long-duration spaceflight.

PMID- 12184343
TI  - Human factors and life support issues in crew rescue from the International Space
      Station (ISS).
AB  - The design and development of crew emergency response systems, particularly to
      provide an unplanned emergency return to earth, requires an understanding of crew
      performance challenges in space. The combined effects of psychological and
      physiological adaptation during long duration missions will have a significant
      effect on crew performance in the unpredictable and potentially life threatening
      conditions of an emergency return to earth. It is therefore important that the
      systems to be developed for emergency egress address these challenges through an
      integrated program to produce optimum productivity and safety in times of utmost
      stress. Fundamental to the success of the CRV is the Environmental Control and
      Life Support System (ECLSS), which provides the necessary conditions for the crew
      to survive their return mission in a shirt-sleeve environment. This paper will
      discuss the many issues in the design of an ECLSS system for CRV and place it in
      the context of the human performance challenges of the mission.

PMID- 12184344
TI  - High performance team interaction in an air medical program.
AB  - The purpose of this qualitative study was to identify and describe the elements
      of a high performance team interaction on an air medical transport mission.
      METHODS: The phenomenologic method as described by Giorgi was used to guide data
      collection and analysis. Six flight nurses from around the United States were
      interviewed and audiotaped as they described their subjective perception of a
      high performance team experience. RESULTS: Four themes emerged from the data:
      collaboration, mutual respect and trust, fitness standards, and synergy.
      CONCLUSION: Implications for flight crews involved in this high performance
      environment may require attention to the identified themes to promote team
      performance.

PMID- 12184345
TI  - Some influences of the physical environment on human cognition.
AB  - The value of human work, even when it is primarily physical, arises from unique
      cognitive capabilities. This paper samples a broadly distributed research base
      regarding influences of the physical environment on human cognition. The
      presentation draws primarily on studies conducted within the context of dynamic
      physical domains of work, to address controls and information sources for
      enabling human intervention, and related reasoning and planning. Several examples
      illustrate the role of the environment as a source of information and as an
      influence on the sequencing of work activity. Life support is discussed both as
      an instance of a dynamic physical system, and for its potential to preclude
      direct engagement with the environment, with predictable cognitive consequences.

PMID- 12184346
TI  - Consumer involvement in CAM research.

PMID- 12184347
TI  - A pilot study to evaluate the effectiveness of Bowen technique in the management
      of clients with frozen shoulder.
AB  - OBJECTIVE: To evaluate clients' experience of Bowen Technique in the treatment of
      frozen shoulder in terms of their pain, functional ability and well-being.
      DESIGN: A case series that used primarily quantitative methods and qualitative
      interviews. PARTICIPANTS: Twenty participants with frozen shoulder. INTERVENTION:
      Bowen Technique, using 'frozen shoulder procedure'. MAIN OUTCOME MEASURES: Range
      of active and passive motion (abduction, flexion, extension, medial rotation,
      lateral rotation and 'wall climb') in both shoulders, pain intensity scores,
      impact on well-being and health status. MAIN RESULTS: Improvement in shoulder
      mobility and associated function for all participants. Median 'worst pain' pre
      therapy score reduced from 7 (mean 7, range 1-10) to a median 'worst pain' score
      of 1 (mean 1.45, range 0-5) post-therapy. Fewer pain quality descriptors used by
      all participants. All participants experienced improvement in their daily
      activities. CONCLUSIONS: Bowen Technique demonstrated an improvement for
      participants, even those with a very longstanding history of frozen shoulder.
      Further trials are warranted.

PMID- 12184349
TI  - 'An empty and happy feeling in the bladder.. .': health changes experienced by
      women after acupuncture for recurrent cystitis.
AB  - OBJECTIVE: The aim of this study was to explore changes in health as reported by
      cystitis-prone females after having received prophylactic acupuncture treatment
      for recurrent cystitis. DESIGN: A qualitative study based on written free text
      answers on the women's own experience of changes related to health after
      completion of TCM acupuncture treatment. Data were analyzed using Giorgi's
      phenomenological approach. SETTING: Subjects living in the Bergen area, Norway,
      were recruited by advertisement in local newspapers and included provided they
      had had three or more episodes of lower UTI during the previous 12 months.
      RESULTS: The main topics reported were related to improved pressure during
      micturition and more complete bladder emptying; more normal bowel movement and
      less abdominal discomfort; more energy, reduced stress level, and better sleep.
      Only a few reported feeling worse. CONCLUSION: The symptoms described as relieved
      by the women in our study seem to fit TCM theory for diagnoses of their
      vulnerability to cystitis. Qualitative methods have a role in TCM research that
      may enrich our knowledge in other ways than traditional quantitative methods may.

PMID- 12184348
TI  - Six-month depression relapse rates among women treated with acupuncture.
AB  - Conventional treatments for Major Depression, although reasonably effective,
      leave many without lasting relief. Alternative approaches would therefore be
      welcome for both short- and long-term treatment of depression. Thirty-eight women
      were randomized to one of three treatment conditions in a double-blind randomized
      controlled trial of acupuncture in depression. All participants eventually
      received eight weeks of acupuncture treatment specifically for depression. From
      among the 33 women who completed treatment, 26 (79%) were intertiewed at six
      month follow-up. Relapse rates were comparable to those of established
      treatments, with four of the 17 women (24%) who achieved full remission at the
      conclusion of treatment experiencing a relapse six months later. Compared to
      other empirically validated treatments, acupuncture designed specifically to
      treat major depression produces results that are comparable in terms of rates of
      response and of relapse or recurrence. These results suggest a larger trial of
      acupuncture in the acute- and maintenance-phase treatment of depression is
      warranted.

PMID- 12184350
TI  - Sociocultural factors influencing adolescent preference and use of native
      Hawaiian healers.
AB  - OBJECTIVE: Few studies have examined the use of alternative therapies among
      adolescents. This study examines the predictors of Native Hawaiian healer
      preference in the treatment of physical or emotional problems as well as the
      predictors of healer use. DESIGN: This study is a longitudinal cross-sectional
      design. SETTING: The survey was conducted in five high schools in Hawai'i.
      PARTICIPANTS: 1,322 high school students selected preference for and/or use of
      allopathic or alternative practitioners. MAIN OUTCOME MEASURES: Grade level,
      gender, ethnicity and cultural identity were used to predict healer preference.
      Healer preference, socioeconomic status and health status were used to predict
      healer use. RESULTS: Identification with the Hawaiian culture was the strongest
      predictor of healer preference for both Hawaiian and non-Hawaiian adolescents.
      Mental health was also predictive of healer preference for non-Hawaiians. Healer
      use by Native Hawaiian adolescents was also predicted by Hawaiian cultural
      identity. Gender, grade level, and socioeconomic variables were not predictive of
      healer preference or use. CONCLUSION: Cultural identity plays a significant role
      in the preference and use of alternative practitioners, especially for minority
      adolescent populations.

PMID- 12184351
TI  - Complementary and alternative medicine use in the Amish.
AB  - OBJECTIVE: To examine the rate of utilization of complementary and alternative
      medicine (CAM) in Amish women, a population that traditionally uses non
      mainstream medicine. METHODS & RESULTS: Sixty-six Amish women completed a survey
      concerning their use of CAM. Thirty-six percent of the Amish women used at least
      one form of CAM, primarily reporting a use of diet and nutrition programs, herbal
      therapies, and chiropractic medicine. In addition, ten pregnant Amish women
      reported using echinacea, St. John's Wort, red clover, garlic and ginseng.
      CONCLUSION: This survey highlights the need to address potential adverse effects
      of herbal therapies in young women who are a member of a group that may use non
      mainstream medicine.

PMID- 12184352
TI  - How to reduce the number of patients needed for randomized trials: a basic
      introduction.
AB  - Complementary therapies are often used to treat patients with persisting
      conditions. In a typical randomized trial, patients are assessed for symptom
      severity at baseline, randomized to treatment or control and then reassessed
      after a suitable follow-up period. It can be shown that the number of patients
      required for such trials can be reduced by the use of two methods: repeat
      measurement and analysis of co-variance (ANCOVA). An example is given of a trial
      of acupuncture for back pain. Administering the pain questionnaire twice at
      baseline and four times at follow-up reduces the number of patients by
      approximately 20% compared to single questionnaire administration. Use of ANCOVA
      decreases the number of patients by approximately a further 10%. There are
      considerable economic and ethical advantages to reducing sample size by a third;
      however, ANCOVA is statistically complex and expert statistical help is required.

PMID- 12184354
TI  - Standards for reporting interventions in controlled trials of acupuncture: the
      STRICTA recommendations.
AB  - Acupuncture treatment and control group interventions in parallel-group
      randomised trials of acupuncture are not always precisely reported. In an attempt
      to improve standards, an international group of experienced acupuncturists and
      researchers devised a set of recommendations, designating them STRICTA: STandards
      for Reporting Interventions in Controlled Trials of Acupuncture. In a further
      consensus-building round, the editors of several journals helped redraft the
      recommendations. These follow the Consolidated Standards for Reporting Trials
      (CONSORT) format, acting as an extension of the CONSORT guidelines for the
      specific requirements of acupuncture studies. Participating journals are
      publishing the STRICTA recommendations and requesting prospective authors to
      adhere to them when preparing reports for publication. Other journals are invited
      to adopt these recommendations. The intended outcome is that interventions in
      controlled trials of acupuncture will be more adequately reported, thereby
      facilitating an improvement in critical appraisal, analysis and replication of
      trials.

PMID- 12184353
TI  - Clinical trials of acupuncture: consensus recommendations for optimal treatment,
      sham controls and blinding.
AB  - Evidence of effectiveness is increasingly used to determine which health
      technologies are incorporated into public health provision. Acupuncture is a
      popular therapy that has been shown to be superior to placebo in the treatment of
      nausea and dental pain, and promising for migraine and osteoarthritis of the
      knee. For many other conditions, such as chronic pain, in which acupuncture is
      often used, the evidence is either insufficient or negative. Misleading results
      may occur for a number of reasons. False negative results may arise from
      inadequate treatment schedules and inappropriate control interventions. This
      consensus document considers these issues with the aim of improving the design of
      efficacy trials of acupuncture in order that they are more likely to be
      conclusive and more meaningfully interpreted. Clinical trials of acupuncture must
      use an optimal form of treatment; this can be defined by examining standard
      texts, by surveying and consulting experts. There are a great many variables in
      treatment (such as point selection, form of stimulation) all of which need to be
      addressed in designing and reporting clinical trials. The control procedure is
      determined by the precise research question that is being addressed. For efficacy
      studies, in which the question is whether acupuncture has specific effects (i.e.
      is superior to placebo), sham forms of acupuncture appear the most appropriate
      method of controlling for needle penetration. A recent development of blunted,
      telescopic needles may represent a major advance. Such procedures may produce a
      therapeutic response so should preferably be recorded as 'sham' procedures rather
      than true 'placebo' controls. Blinding in clinical trials is an accepted means of
      reducing bias. Patient blinding in acupuncture studies can be achieved by sham
      procedures and its success should be measured. While practitioner blinding is
      difficult, though not impossible, blinding of the observer and the analyst should
      be considered as the ideal for all studies. A number of recommendations are made
      which aim to improve the quality of sham-controlled acupuncture studies.

PMID- 12184355
TI  - Educating health professionals about how to use the Web and how to find
      complementary and alternative medicine (CAM) information.

PMID- 12184356
TI  - 'Alternative medicine bias.

PMID- 12184357
TI  - The attitudes to and use of complementary medicine among physicians in the UK.

PMID- 12184358
TI  - Workshop summary. Aluminum in vaccines.

PMID- 12184359
TI  - Aluminum toxicokinetics regarding infant diet and vaccinations.
AB  - Some vaccines contain aluminum adjuvants to enhance the immunological response,
      and it has been postulated that this aluminum could contribute to adverse health
      effects, especially in children who receive a vaccination series starting at
      birth. The pharmacokinetic properties and end-point toxicities of aluminum are
      presented. In assessing the relevance of dietary and medical aluminum exposure to
      public health, we estimated infant body burdens during the first year of life for
      breast milk and formula diets and for a standard vaccination schedule. We then
      compared those body burdens with that expected for intake at a level considered
      safe for intermediate-duration exposure. The methodology blends intake values and
      uptake fractions with an aluminum retention function derived from a human
      injection study using radioactive 26Al. The calculated body burden of aluminum
      from vaccinations exceeds that from dietary sources, however, it is below the
      minimal risk level equivalent curve after the brief period following injection.

PMID- 12184360
TI  - Aluminum salts in vaccines--US perspective.
AB  - Aluminum in the form of aluminum hydroxide, aluminum phosphate or alum has been
      commonly used as an adjuvant in many vaccines licensed by the US Food and Drug
      Administration. Chapter 21 of the US Code of Federal Regulations [610.15(a)]
      limits the amount of aluminum in biological products, including vaccines, to 0.85
      mg/dose. The amount of aluminum in vaccines currently licensed in the US ranges
      from 0.85-0.125 mg/dose. Clinical studies have demonstrated that aluminum
      enhances the antigenicity of some vaccines such as diphtheria and tetanus
      toxoids. Moreover, aluminum-adsorbed diphtheria and tetanus toxoids are
      distinctly more effective than plain fluid toxoids for primary immunization of
      children. There is little difference between plain and adsorbed toxoids for
      booster immunization. Aluminum adjuvants have a demonstrated safety profile of
      over six decades; however, these adjuvants have been associated with severe local
      reactions such as erythema, subcutaneous nodules and contact hypersensitivity.

PMID- 12184361
TI  - The global impact of vaccines containing aluminium adjuvants.
AB  - Immunization against childhood vaccine-preventable diseases has arguably had the
      greatest impact on the health of children of any public health intervention. Many
      of the vaccines used in the Expanded Programme on Immunization (EPI) have
      contained aluminium-based adjuvants. As such, these adjuvants have played a vital
      role in enabling the basic vaccines to be used effectively. DTP global supply is
      fragile and could easily be upset through the loss of even one major vaccine
      manufacturer. Non-aluminium adjuvants could not readily replace aluminium
      adjuvants. New generation vaccines will probably need new generation adjuvants.
      The impact of vaccines with adjuvants is discussed. Having provided decades of
      reliable, safe service in their relatively simple chemical formulations,
      adjuvants are likely to be with us, in one form or another, for the indefinite
      future.

PMID- 12184362
TI  - Mechanisms of stimulation of the immune response by aluminum adjuvants.
AB  - Aluminum adjuvants are widely used in human and veterinary vaccines. They are
      appropriate adjuvants for vaccines that confer protection by inducing antibodies
      via the induction of a type 2 immune response, but they do not induce cytotoxic T
      cell and cell-mediated immunity. The mechanisms by which aluminum adjuvants
      selectively enhance the immune response are poorly understood. Following exposure
      to interstitial fluid in vitro and in vivo, most antigens are rapidly desorbed
      from aluminum adjuvants, suggesting that sustained release of antigen from a
      depot does not significantly contribute to the adjuvant effect of aluminum
      compounds. However, the adsorption of antigens onto aluminum salts may result in
      a high local concentration of antigen at the injection site and enhance the
      uptake by antigen-presenting cells. Aluminum compounds can further enhance the
      immune response by direct or indirect stimulation of dendritic cells, activation
      of complement and by inducing the release of chemokines. The relative importance
      of these mechanisms remains to be determined.

PMID- 12184363
TI  - Elimination of aluminum adjuvants.
AB  - In vitro dissolution experiments although perhaps not at typical body
      concentrations and temperatures demonstrated that the alpha-hydroxycarboxylic
      acids present in interstitial fluid (citric acid, lactic acid, and malic acid)
      are capable of dissolving aluminum-containing adjuvants. Amorphous aluminum
      phosphate adjuvant dissolved more rapidly than crystalline aluminum hydroxide
      adjuvant. Intramuscular administration in New Zealand White rabbits of aluminum
      phosphate and aluminum hydroxide adjuvants, which were labelled with 26Al,
      revealed that 26Al was present in the first blood sample (1 h) for both
      adjuvants. The area under the blood level curve for 28 days indicated that three
      times more aluminum was absorbed from aluminum phosphate adjuvant than aluminum
      hydroxide adjuvant. In vivo studies using 26Al-labelled adjuvants are relatively
      safe because accelerator mass spectrometry (AMS) can quantify quantities of 26Al
      as small as 10(-17) g. A similar study in humans would require a whole-body
      exposure of 0.7 microSv per year compared to the natural background exposure of
      3000 microSv per year. The in vitro dissolution and in vivo absorption studies
      indicate that aluminum-containing adjuvants which are administered
      intramuscularly are dissolved by alpha-hydroxycarboxylic acids in interstitial
      fluid, absorbed into the blood, distributed to tissues, and eliminated in the
      urine.

PMID- 12184364
TI  - Lack of consistent relationship between quantity of aluminum in diphtheria
      tetanus-acellular pertussis vaccines and rates of extensive swelling reactions.
AB  - The precise role that aluminum plays in local reactogenicity is not clear. We
      explored the relationship between rates of severe local reactions following the
      fourth and fifth booster doses of several diphtheria-tetanus-acellular pertussis
      vaccines (DTaP) and the quantity of aluminum contained in the different vaccines.
      Although there was a significant relationship between higher aluminum contents
      and swelling reactions >50 mm after dose 5, no relationship was seen with entire
      thigh swelling or with swelling >50 mm after dose 4. Because of the inconsistency
      of the data, a dose response between local reactogenicity and aluminum is
      questionable.

PMID- 12184365
TI  - Aluminum-containing vaccine associated adverse events: role of route of
      administration and gender.
AB  - Anthrax vaccine, adsorbed (AVA) is a vaccine containing aluminum hydroxide that
      is administered as six subcutaneous (s.q.) doses over 18 months. It is the only
      aluminum hydroxide licensed for s.q. administration. To optimize the vaccination
      schedule and route of administration, a prospective pilot study comparing the use
      of fewer doses administered intramuscularly (i.m.) as well as s.q. with the
      licensed schedule and route was performed. Data from that study on injection site
      reactions were extracted for this report. Erythema and induration occurred more
      commonly when the vaccine was administered s.q. compared to i.m. (P < 0.0001, P =
      0.002, respectively). S.q. nodules were found only among the s.q. group (P <
      0.0001). Erythema, induration and s.q. nodules were more common in women compared
      with men (P < 0.001) after the first s.q. dose of AVA dose. Reaction rates
      decreased when the interval between the first two doses of AVA was increased from
      2 to 4 weeks.

PMID- 12184366
TI  - Macrophagic myofasciitis: a summary of Dr. Gherardi's presentations.
AB  - Dr. R.K. Gherardi presented two papers at the symposium, detailing his researches
      into a proposed new clinical entity which he has entitled Macrophagic
      Myofasciitis (MMF). In his first paper he described the histopathologic and
      immunologic characteristics of the condition, and in the second, the clinical and
      serologic features. Dr. Gherardi believes that MMF, a syndrome of ascending
      myalgias, fatigue and diffuse musculoskeletal pain, may be related to a chronic
      immune response to aluminum granulomas persisting at the sites of prior
      immunization with aluminum adjuvated vaccines.

PMID- 12184367
TI  - Considerations and procedures in the derivation of ATSDR minimal risk levels.
AB  - Minimal risk levels (MRLs) are health-based guidance values derived for
      individual substances by conducting a thorough review of the literature,
      identifying appropriate target organs of response, and identifying a dose level
      where a no adverse effect or the lowest adverse effect level is seen. This level
      is then evaluated for uncertainty in the data base and for other extenuating
      factors and subsequently adjusted with uncertainty or modifying factors. The
      resulting calculation yields the MRL that is defined as an estimate of the daily
      human exposure to a hazardous substance that is likely to be without appreciable
      risk of adverse noncancer health effects over a specified duration of exposure.
      Typically, MRLs are derived for different durations of exposure (acute,
      intermediate, chronic) and for different routes of exposure (oral, inhalation).
      The MRLs serve as useful reference values in evaluating human health from
      exposure to substances found at hazardous waste sites. Because of numerous
      requests of various programs, recent work has focused on expanding the
      applicability of MRLs to other situations and routes of exposure (dermal, food
      supply, intramuscular) beyond the traditional oral and inhalation exposure routes
      at waste sites. Results of work, in conjunction with the Agency for Toxic
      Substances and Disease Registry's computational toxicology laboratory, shows that
      the use of computational methods, such as physiologically based pharmacokinetic
      modeling, may allow the MRL process to be adapted to unique durations and routes
      of exposure such as intramuscular injections.

PMID- 12184368
TI  - Design and selection of vaccine adjuvants: animal models and human trials.
AB  - The availability of hundreds of different adjuvants has prompted a need for
      identifying rational standards for selection of adjuvant formulations based on
      safety and sound immunological principles for human vaccines. Although many of
      the mechanisms of adjuvants have been elucidated, meaningful comparisons between
      different adjuvants derived from in vitro studies, or from studies using
      adjuvants in rodents or other animals, are often not predictive for safety,
      adjuvant effects, or vaccine efficacy in humans. A highly efficient and cost
      effective method for comparison of adjuvants with a new antigen is to conduct
      multiple small-scale, phase 1, comparative studies in humans with a new antigen,
      using adjuvants previously found to be safe with other antigens in human trials.
      Studies in which highly immunogenic and safe adjuvant formulations have been
      evaluated in comparative adjuvant trials in humans using a single candidate
      vaccine antigen against malaria, HIV, and prostate cancer with multiple adjuvants
      are reviewed.

PMID- 12184369
TI  - Overview of vaccine adjuvants: present and future.
AB  - The history of infectious diseases together with the evidence of emerging and
      reemerging infections underscores the need for new vaccines and the obstacles to
      producing them. Vaccine adjuvants are usually thought of as agents that increase
      the intensity of immune responses and influence the balance between antibody and
      cell-mediated immunity at the cost of toxicity. This review uses copolymer
      adjuvants as examples to encourage a more sophisticated approach to the study of
      adjuvants as agents that can influence many parameters of immune responses
      including the specificity, titer, duration, memory, class, isotype, and avidity
      of antibody as well as the type of cell-mediated immunity and the incidence of
      genetic non-responders. Much research will be needed for design of effective
      vaccines against emerging and reemerging infections and for improvement of
      existing vaccines.

PMID- 12184370
TI  - Type 1 protein tyrosine kinases in breast carcinoma: a review.
AB  - One of the most studied onco-gene families in breast tumors is the type 1 protein
      tyrosine kinase family, which consists of EGFR, c-erbB-2, c-erbB-3, and c-erbB-4.
      Overexpression of c-erbB-2 protein/mRNA in breast carcinomas is consistently
      associated with poor prognosis, while EGFR overexpression has been confirmed to
      have a synergistic clinical effect on the c-erbB-2 influence. The expression
      pattern of c-erbB-4 in breast carcinomas is special. Unlike other type 1 protein
      tyrosine kinases, expression of c-erbB-4 protein/mRNA is reduced in carcinomas
      compared with that in normal breast epithelia, and its expression has also been
      associated with a better clinical outcome, indicating the need for c-erbB-4
      analysis when clinical therapeutic application of EGFR and c-erbB-2 anitbodies is
      considered. In addition, studies of the adaptor proteins in breast carcinomas are
      highly indicated in order to clarify the mechanisms behind the dysregulated
      expression of such receptors in breast carcinomas.

PMID- 12184371
TI  - Ultrastructural and biophysical studies on protein conformations of epithelium
      and stroma in benign prostatic hyperplasia before and after transurethral
      resection of the prostate.
AB  - The alterations in protein conformation of epithelium and stroma in human benign
      prostatic hyperplasia (BPH) undergoing prostatic needle biopsy (PNB) and
      transurethral resection of the prostate (TURP) were isolated in vitro and
      investigated using attenuated total reflectance (ATR)/Fourier transform infrared
      (FT-IR) microspectroscopy. Second-derivative spectral analysis and a curve
      fitting program were used to verify and obtain the protein secondary conformation
      and composition of the samples. TURP uses an electric cutting heat but PNB is a
      nonheating process. The results indicate a predominantly higher proportion of
      beta-sheet conformation of the epithelium or stroma in BPH tissue at 1633 or 1630
      cm(-1) in the amide I band, but after treatment with TURP, both maximum peaks
      shifted to 1644 or 1646 cm(-1) due to random coil structure, respectively. This
      conversion suggests that the heat generated by the cutting loop could increase
      the temperature in the tissue surrounding the prostate, thereby modifying the
      protein conformational structure of epithelium and stroma in BPH tissue.

PMID- 12184372
TI  - Bone marrow leukemias and lymphoproliferative disorders: scanning electron
      microscope diagnosis.
AB  - This work considers the primary diagnosis of bone marrow leukemias and
      lymphoproliferative disorders by using the scanning electron microscope (SEM). A
      total of 14 cases are studied, including 2 demonstrating bone marrow hyperplasia
      only. The utility of employing the ordinary pathology glass microslide with
      routine stain is emphasized, as well as certain capabilities of the SEM,
      including backscattered electron image, secondary electron image, and measurement
      program. Bone marrow hyperplasias, myeloid leukemias, and lymphoproliferative
      disorders are analyzed by comparing specific ultrastructural features, such as
      cell sizes, nuclear chromatin configuration and composition, nucleoli, nuclear
      contour, and cytoplasmic constituents, including granule population with sizes of
      such granules. These features set apart the common bone marrow neoplasms and can
      be a determinant in case diagnosis.

PMID- 12184374
TI  - Ultrastructural changes in a standard strain of Bartonella henselae after
      passages through BALB/cAn mice.
AB  - Human bartonelloses are a group of illnesses of poorly understood pathogenesis.
      Bartonella henselae is one of the most studied bacterium of its genus. The
      objective of this study was to observe whether passages of these bacteria, in
      vivo, would determine ultrastructural changes in them. For this purpose, isogenic
      mice were inoculated with a standard strain of B. henselae (I). These were
      initially retrieved from genetically immunodeficient animals (II) and then
      inoculated in immunocompetent ones. The bacterial colonies obtained (III) were
      compared, by transmission electron microscopy, with colonies I and II. Loss of
      fimbriae and an abundant bleb formation were the most common morphological
      changes found in colony III. Also, on day 6 postinfection, the main histological
      abnormalities were the endothelial proliferation presented in immunodeficient
      animals and the incipient granulomata reaction found in one of the
      immunocompetent inoculated mice, which died spontaneously. These features agree
      with the Bartonella human disease clinical and histological observations. This
      study demonstrates that B. henselae in vivo passages induce significant
      morphological changes in the bacteria and that these abnormalities could explain
      their seemingly greater virulence. Most of these observations have not been
      previously described. Thus, further studies on the Bartonella species
      pathogenesis should consider these data.

PMID- 12184373
TI  - Detection of gold particles in the neck skin after lightning stroke with
      evaporation of an ornamental chain.
AB  - A German couple was struck by lightning. Both patients survived this event.
      Whereas the husband was unconscious for only a few minutes, his wife fell into
      coma for 24 h. The lightning stroke entered the body of the woman behind the left
      ear and left it at the left shoe. The stroke caused a partial evaporation of a
      gold ornamental chain on the neck, resulting in a tattoo of the neck skin. A
      biopsy of the skin 6 months after the event showed the accumulation of gold
      particles of different size in the dermis down to the subcutaneous fatty tissue.
      In semithin sections, histiocytes, multinucleated foreign giant cells, and
      fibroblasts were visible with uptaken metallic particles. In transmission
      electron microscopy, gold globules of up to 30 microm in diameter were visible
      outside the cells in the collageneous matrix of the connective tissue besides
      smaller metallic particles up to 5 nm inside lysosomes and residual bodies of
      phagocytic cells. Four different kinds of gold particles could be differentiated:
      globules, granular irregular particles, tubules, and tanglelike tracks. In
      scanning electron microscopy, gold particles were demonstrated by backscatter
      detection in the connective tissue of subcutis, where the EDX elemental analysis
      showed strong signals of aurum (Au), copper (Cu), and argentum (Ag). The detected
      metals were quantified by AAS as 70% gold, 21% silver, and 9% copper, which
      demonstrates the composition of gold alloy of the neck chain of the patient.
      Tanglelike tracks and elongated gold deposits represent crystals of gold salts,
      as detected by electron diffraction and polarization microscopy. Attempts to
      remove the gold particles from the skin to remove the tattoo should not be
      undertaken because the gold is deep and widespread.

PMID- 12184375
TI  - Bone and ceramic interaction in the bone union process.
AB  - This study applied an experimental rat model and ceramic as an artificial matrix
      to explore the ultrastructural development of new bone production in tibia
      defects. By X-ray diffraction control or energy-dispersive X-ray analysis the
      nature of ceramic was verified and routine histology and TEM investigation were
      used to demonstrate bone - ceramic interaction. The results show that biphasic
      ceramic can promote bone growth in an osseous defect and is therefore an
      alternative to autogenous bone matrix. The porousity and bioactivity of the
      biphasic ceramic enhanced bone formation and provided a scaffold for new lamellar
      bone invasion.

PMID- 12184376
TI  - Giant mitochondria in a cardiomyopathic heart.
AB  - Giant mitochondria (megamitochondria) measuring up to 14 microm in length and 3
      microm in width are sporadically present in an exclusively interfibrillar
      position in the cardiomyocytes of a patient with restrictive cardiomyopathy. The
      number of cristae is augmented in the megamitochondria; these internal membranes
      are for the most part irregularly arrayed, but in certain giant mitochondria they
      run a parallel, zigzag course imparting a paracrystalline appearance to such
      organelles. Many of the giant mitochondria have one or several lucent, single
      membrane-bound inclusions that contain either alpha- or beta-glycogen particles.
      Megamitochondria probably originate at least in part by fusion of adjacent
      organelles.

PMID- 12184378
TI  - Case for the panel. Virus-like particles within bile canaliculi.

PMID- 12184377
TI  - An ultrastructural study of cutaneous panniculitis-like T-cell lymphoma:
      cytoplasmic granules and active cellular and cell-to-matrix interaction mimic
      cytotoxic T-cells.
AB  - Subcutaneous panniculitis-like T-cell lymphoma (SPTCL) is a rare type of
      peripheral T-cell-derived lymphoma. A 30-year-old Japanese woman presented,
      complaining of skin lesions on her left hip. The cellular constituents in this
      SPTCL were of a mixed population. Not only tumor lymphoid cells, but also many
      macrophages, endothelial, fibroblasts, and fat cells were seen. The tumor cells
      immunostained positive for CD3 and CD8, but negative for CD4. Cytotoxic injury
      granule-related antigens of TIA-1 and granzyme B were positive in tumor cells.
      CD30. CD56, EBNA-2, LMP-1, CD20cy, and CD68 were all negative in the tumor cells.
      An ultrastructural study revealed that the lymphoma cells showed primitive
      cellular contacts with the neighboring tumor cells, interacted with the short
      villous dendrites of the opposing macrophage and fibroblast cellular membranes,
      and were associated with the vascular constituents, fat cells, and the
      extracellular matrix. Small aggregations of the granules were frequently seen in
      the cytoplasm. It was speculated that the tumor cells to some extent preserve the
      cytotoxic T-cell structure and function, have active cellular and cell-to-matrix
      interaction, contain characteristic cytoplasmic granules, and reveal unique
      histology like panniculities.

PMID- 12184379
TI  - Integration of chemical data using XML.
AB  - Internet resources for the toxicological and pharmacological communities offer
      considerable information, however, the data is generally not amenable to machine
      driven reuse. Adoption of XML standards by these (and related) communities will
      revolutionize the process of sharing information, promoting collaboration and
      discovery.

PMID- 12184380
TI  - Can the Internet help to meet the challenges in ADME and e-ADME?
AB  - The high-throughput screening (HTS) of large proprietary compound collections and
      combinatorial libraries has put an increased pressure on getting pharmacokinetic
      and drug metabolism data as early as possible. Properties related to absorption,
      distribution, metabolism and excretion (ADME) can be estimated by a range of in
      vivo and in vitro methods. Most are now available or under development in
      high(er) throughput modus. In addition progress has been made in in silico
      methods using various QSAR and modeling techniques using a range of recently
      introduced descriptors tailored to e-ADME. These approaches are promising as a
      filter for virtual libraries to decide on synthesis as well as in the selection
      of compounds for acquisition and screening. This paper will discuss a number of
      Internet resources relevant to ADME studies and predictions. We have focused on
      areas related to metabolism including metabolic pathways and P450 metabolism,
      transporters, bioavailability and absorption, pharmacokinetics and
      pharmacodynamics, molecular properties and tools for data analysis.

PMID- 12184381
TI  - WWW small molecule modeling.
AB  - Computational chemistry and molecular modeling sites have proliferated on the
      Internet's world wide web. This paper provides present links to some of the more
      most useful ones for small organic molecule modeling, and offering free
      resources.

PMID- 12184382
TI  - e-statistics for deriving QSAR models.
AB  - This paper presents some freeware, shareware, and commercial statistical tools
      available via the Internet and which could be used in QSAR for deriving models.
      Programming environments useful in Statistics, newsgroups and FAQs are also
      introduced due to their interest for the discipline.

PMID- 12184383
TI  - Variable selection for QSAR by artificial ant colony systems.
AB  - Derivation of quantitative structure-activity relationships (QSAR) usually
      involves computational models that relate a set of input variables describing the
      structural properties of the molecules for which the activity has been measured
      to the output variable representing activity. Many of the input variables may be
      correlated, and it is therefore often desirable to select an optimal subset of
      the input variables that results in the most predictive model. In this paper we
      describe an optimization technique for variable selection based on artificial ant
      colony systems. The algorithm is inspired by the behavior of real ants, which are
      able to find the shortest path between a food source and their nest using
      deposits of pheromone as a communication agent. The underlying basic self
      organizing principle is exploited for the construction of parsimonious QSAR
      models based on neural networks for several classical QSAR data sets.

PMID- 12184384
TI  - Predictive Array Design. A method for sampling combinatorial chemistry library
      space.
AB  - A method, Predictive Array Design, is presented for sampling combinatorial
      chemistry space and selecting a subarray for synthesis based on the experimental
      design method of Latin Squares. The method is appropriate for libraries with
      three sites of variation. Libraries with four sites of variation can be designed
      using the Graeco-Latin Square. Simulated annealing is used to optimise the
      physicochemical property profile of the sub-array. The sub-array can be used to
      make predictions of the activity of compounds in the all combinations array if we
      assume each monomer has a relatively constant contribution to activity and that
      the activity of a compound is composed of the sum of the activities of its
      constitutive monomers.

PMID- 12184385
TI  - Computer-aided prediction of receptor profile for drug-like compounds.
AB  - Computer program SIMEST (Similarity Estimating) for prompt estimation of drug
      like compounds' interaction with various receptors has been developed. More than
      200 kinds of receptor activities (agonists and antagonists) can be predicted
      analysing new compound's similarity with known ligands. SIMEST consists of two
      components: (a) database of low-molecular weight ligands (agonists and
      antagonists) for 106 receptors and (b) similarity estimation module based on
      original MNA descriptors. The predictive abilities of SIMEST were evaluated on
      two data sets: (a) about 24,000 biologically active compounds from MDDR-99.2
      database; (b) seven well-studied antipsychotic drugs. Average accuracy of
      prediction was 85.2% for compounds from MDDR and 78.7% for antipsychotic drugs.
      SIMEST can be effectively applied for predicting possible mechanisms of action
      and side effects for drug-like substances on the basis of their structural
      formulae.

PMID- 12184386
TI  - Quantitative prediction of biodegradability, metabolite distribution and toxicity
      of stable metabolites.
AB  - An evaluation of the capability of organic chemicals to mineralize is an
      important factor to consider when assessing their fate in the environment.
      Microbial degradation can convert a toxic chemical into an innocuous one, and
      vice versa, or alter the toxicity of a chemical. Moreover, primary biodegradation
      can convert chemicals into stable products that can be difficult to mineralize.
      In this paper, we present some new results obtained on the basis of a recently
      developed probabilistic approach to modeling biodegradation based on microbial
      transformation pathways. The metabolic transformations and their hierarchy were
      calibrated by making use of the ready biodegradability data from the MITI-I test
      and expert knowledge for the most probable transformation pathways. A model was
      developed and integrated into an expert software system named CATABOL that is
      able to predict the probability of biodegradation of organic chemicals directly
      from their structure. CATABOL simulates the effects of microbial enzyme systems,
      generates the most plausible transformation pathways, and quantitatively predicts
      the persistence and toxicity of the biodegradation products. A subset of 300
      organic chemicals were selected from Canada's Domestic Substances List and
      subjected to CATABOL to compare predicted properties of the parent chemicals with
      their respective first stable metabolite. The results show that most of the
      stable metabolites have a lower acute toxicity to fish and a lower
      bioaccumulation potential compared to the parent chemicals. In contrast, the
      metabolites appear to be generally more estrogenic than the parent chemicals.

PMID- 12184387
TI  - Computer aided prediction of biological activity spectra: evaluating versus known
      and predicting of new activities for thiazole derivatives.
AB  - Computer aided prediction of biological activity spectra by the computer program
      PASS was applied to a set of 89 new thiazole derivatives. Experimentally tested
      activities (NSAID, local anaesthetic and antioxidant) coincide with the
      experiment in 70.8% cases, that exceeds significantly the random guess-work
      (approximately 0.1%). Therefore, computer aided prediction using the Prediction
      of Activity Spectra for Substances (PASS) system (http://www.ibmh.msk.su/PASS)
      provides a reliable basis for planning of synthesis and experimental study for
      new compounds. New psychotropic activities are predicted for some compounds from
      the series under study. In particular, 7, 44 and 55 compounds likely have
      anxiolytic, anticonvulsant and cognition enhancer effects, respectively. Most of
      these compounds have the estimated values of probability to be active (Pa) less
      than 60%. Therefore, if their activity will be confirmed by the experiment, they
      might occur to be New Chemical Entities.

PMID- 12184389
TI  - Molecular modeling of triazine type MDR modulators using CoMFA and CoMSIA
      approaches.
AB  - In the present study a series of 30 triazine derivatives was investigated by 3D
      QSAR methods with respect to their MDR reversing activity in vitro. Two
      approaches were applied and compared: comparative molecular field analysis
      (CoMFA) and comparative molecular similarity indices analysis (CoMSIA). Molecular
      models with good predictive power were derived using steric, electrostatic and
      hydrophobic fields of the compounds. The results indicated the dominant role of
      the electrostatic and hydrophobic fields for MDR reversing activity of the
      investigated modulators. The obtained statistical parameters (Qcv2, Qpr2) showed
      that the CoMFA and CoMSIA models have similar predictivity. The CoMSIA models
      were slightly better than the CoMFA ones and obtained with lower number of
      principal components. The models were graphically interpreted using CoMFA and
      CoMSIA contour plots. The structural regions responsible for the differences in
      anti-MDR activity were analyzed in respect to their electrostatic and hydrophobic
      nature. An easier interpretation of the CoMSIA contour plots was noticed.

PMID- 12184388
TI  - Protein structure prediction and biomolecular recognition: from protein sequence
      to peptidomimetic design with the human beta3 integrin.
AB  - Computational tools can bridge the gap between sequence and protein 3D structure
      based on the notion that information is to be retrieved from the databases and
      that knowledge-based methods can help in approaching a solution of the protein
      folding problem. To this aim our group has implemented neural network-based
      predictors capable of performing with some success in different tasks, including
      predictions of the secondary structure of globular and membrane proteins, the
      topology of membrane proteins and porins and stable alpha-helical segments suited
      for protein design. Moreover we have developed methods for predicting contact
      maps in proteins and the probability of finding a cysteine in a disulfide bridge,
      tools which can contribute to the goal of predicting the 3D structure starting
      from the sequence (the so called ab initio prediction). All our predictors take
      advantage of evolution information derived from the structural alignments of
      homologous (evolutionary related) proteins and taken from the sequence and
      structure databases. When it is necessary to build models for proteins of unknown
      spatial structure, which have very little homology with other proteins of known
      structure, non-standard techniques need to be developed and the tools for protein
      structure predictions may help in protein modeling. The results of a recent
      simulation performed in our lab highlights the role of high performing computing
      technology and of tools of computational biology in protein modeling and
      peptidomimetic design.

PMID- 12184391
TI  - Does the odor from sponges of the genus Ircinia protect them from fish predators?
AB  - Caribbean sponges of the genus Ircinia contain high concentrations of linear
      furanosesterterpene tetronic acids (FTAs) and produce and exude low-molecular
      weight volatile compounds (e.g., dimethyl sulfide, methyl isocyanide, methyl
      isothiocyanate) that give these sponges their characteristic unpleasant garlic
      odor. It has recently been suggested that FTAs are unlikely to function as
      antipredatory chemical defenses, and this function may instead be attributed to
      bioactive volatiles. We tested crude organic extracts and purified fractions
      isolated from Ircinia campana, I. felix, and I. strobilina at naturally occurring
      concentrations in laboratory and field feeding assays to determine their
      palatability to generalist fish predators. We also used a qualitative technique
      to test the crude volatile fraction from I. felix and I. strobilina and
      dimethylsulfide in laboratory feeding assays. Crude organic extracts of all three
      species deterred feeding of fishes in both aquarium and field experiments.
      Bioassay-directed fractionation resulted in the isolation of the FTA fraction as
      the sole active fraction of the nonvolatile crude extract for each species, and
      further assays of subfractions suggested that feeding deterrent activity is
      shared by the FTAs. FTAs deterred fish feeding in aquarium assays at
      concentrations as low as 0.5 mg/ml (fraction B, variabilin), while the natural
      concentrations of combined FTA fractions were > 5.0 mg/ml for all three species.
      In contrast, natural mixtures of volatiles transferred from sponge tissue to food
      pellets and pure dimethylsulfide incorporated into food pellets were readily
      eaten by fish in aquarium assays. Although FTAs may play other ecological roles
      in Ircinia spp., these compounds are effective as defenses against potential
      predatory fishes. Volatile compounds may serve other defensive functions (e.g.,
      antimicrobial, antifouling) but do not appear to provide a defense against fish
      predators.

PMID- 12184390
TI  - Effect of ent-labdane diterpenes from Potamogetonaceae on Selenastrum
      capricornutum and other aquatic organisms.
AB  - Twenty ent-labdane diterpenes, isolated from the aquatic plants Ruppia maritima
      and Potamogeton natans, were tested to detect their effects on aquatic organisms
      from different trophic levels. Toxicity tests were performed on aquatic producers
      (the alga Selenastrum capricornutum), and consumers including a rotifer
      (Brachionus calyciflorus), a cladoceran crustacean (Daphnia magna), and two
      anostracan crustaceans (Thamnocephalusplatyurus and Artemia salina). Furano-ent
      labdanes exhibited high toxicity toward all of these organisms. 15,16-Epoxy-12(S)
      hydroxy-8(17),13(16),14-ent-labdatrien-20.19-olide had a high toxicity only
      toward the algae and the rotifers. It was inactive for the crustaceans.

PMID- 12184392
TI  - Chemosensory stimuli for the walking legs of the crayfish Procambarus clarkii.
AB  - Studies of chemoreception in crustaceans have shown that flesh-eating species can
      detect amino acids, nucleotides and derivatives, and amines, while most
      herbivorous and omnivorous species are additionally sensitive to carbohydrates.
      We used extracellular recording techniques to evaluate the effectiveness of a
      range of nitrogen-containing compounds (mostly amino acids), bile acids, and
      carbohydrates in stimulating chemoreceptor cells present in the second and third
      pereopods of the omnivorous crayfish Procambarus clarkii. When applied at a final
      concentration of approximately 100 microM, effective stimuli were trehalose,
      leucine, cellobiose, glycine, sucrose, maltose, and ammonium (from most to least
      effective). The other 17 compounds tested, many chosen because they are potent
      stimuli for other crustaceans, were ineffective stimuli for P. clarkii.
      Concentration-response functions were determined for three single cells that were
      sensitive to ammonium, for five multiunit fibers sensitive to glycine, and for
      six multiunit fibers sensitive to leucine. Thresholds ranged from 10 nM to 10
      micro, functions were generally linear when plotted against the log of the
      stimulus concentration, and there was little evidence of saturation. While P.
      clarkii is sensitive to only seven of 24 compounds tested, the compounds that
      proved stimulatory should serve as cues for location and identification of food
      items preferred by this omnivorous crustacean.

PMID- 12184393
TI  - Antagonism between jasmonate- and salicylate-mediated induced plant resistance:
      effects of concentration and timing of elicitation on defense-related proteins,
      herbivore, and pathogen performance in tomato.
AB  - The jasmonate (JA) and salicylate (SA) signaling pathways in plants provide
      resistance to herbivorous insects and pathogens. It is known that these pathways
      interact, sometimes resulting in antagonism between the pathways. We tested how
      the timing and concentration of elicitation of each pathway influenced the
      interaction between the jasmonate and salicylate pathways measured in terms of
      five biochemical responses and biological resistance to caterpillars and
      bacteria. The salicylate pathway had a stronger effect on the jasmonate pathway
      than did the reverse. The negative signal interaction was generated by two
      distinct paths in the plant. A negative interaction in the biochemical expression
      of the two pathways was most consistent in the simultaneous elicitation
      experiments compared to when the elicitors were temporally separated by two days.
      Herbivore bioassays with Spodoptera exigua also consistently reflected an
      interaction between the two pathways in the simultaneous elicitation experiments.
      The negative signal interaction reducing biological resistance to the herbivore
      was also demonstrated in some temporally separated treatment combinations where
      attenuation of the biochemical response was not evident. Concentration of the
      elicitors had an effect on the pathway interaction with consistent biochemical
      and biological antagonism in the high concentration experiments and inconsistent
      antagonism in the low concentration experiments. The bacterial pathogen,
      Pseudomonas syringae pv. tomato (Pst), consistently showed reduced lesion
      development on plants with SA responses activated and, in some experiments, on JA
      elicited plants. Resistance to Pst was not reduced or enhanced in dual-elicited
      plants. Thus, signal interaction is most consistent when elicitors are applied at
      the same time or when applied at high doses. Signal interaction affected the
      herbivore S. exigua, but not the pathogen Pst.

PMID- 12184394
TI  - Floral synomone of a wild orchid, Bulbophyllum cheiri, lures Bactrocera fruit
      flies for pollination.
AB  - The major fruit fly attractant component in the floral fragrance of Bulbophyllum
      cheiri (fruit fly orchid) is methyl eugenol (ME). In the lowland rain forest of
      Malaysia, the solitary and nonresupinate flowers of the fruit fly orchid attract
      only males of the ME-sensitive fruit fly species (Bactrocera carambolae, B.
      papayae. and B. umbrosa. During the morning, the fruit fly orchid flower is
      visited by many fruit flies, which can sometimes cover the whole flower. The
      number of visitors dwindles in the afternoon. Headspace analysis of the flower
      shows a high ME peak in the morning, a small one between 12:00 and 14:00 hr, and
      no detectable ME peak after 14:00 hr. The process of pollination in the wild is
      initiated by attraction of fruit flies to floral ME. The flower, with the aid of
      its specialized hinged see-saw lip (labellum), temporarily traps (< 1 min) a
      fruit fly pollinator between its lip and column. Just prior to this, the fly is
      rewarded by the opportunity to feed on the floral attractant found on surfaces of
      petals, sepals, and lip. The pollinaria borne by two wild B. papayae males
      (caught on and near the fruit fly orchid flower) are identical in morphology and
      structure with those obtained from the flower. Many of the B. papayae males (17
      of 22 analyzed) attracted to the fruit fly orchid already possessed both ME
      metabolites, trans-coniferyl alcohol and 2-allyl-4,5-dimethoxyphenol, in their
      rectal glands. indicating that they had previously consumed ME. In this orchid
      fruit fly association, both organisms gain direct reproductive benefits: the
      orchid flower gets pollinated without having to offer nectar, while the fruit fly
      boosts its pheromone and defense system, as well as its sexual competitiveness by
      feeding on the ME produced by the flower.

PMID- 12184395
TI  - Allelopathic potential and chemical constituents of volatiles from Ageratum
      conyzoides under stress.
AB  - The allelopathic potential of Ageratum conyzoides was investigated under
      different environmental stress conditions, including nutrient deficiency.
      physical damage, 2.4-D treatment, competition with Bidens pilosa, infection with
      Erysiphe cichoracearum, and feeding by Aphiids gossypii. The inhibitory effects
      of A. conyzoides volatiles on peanut (Arachis hypogaea), redroot amaranth
      (Amaranthus retroflexus), cucumber (Cucumis sativus), and ryegrass (Lolium
      multiforum) increased when plants were grown under nutrient-deficient conditions
      or in competition with B. pilosa; however, there was no difference with physical
      damage or 2.4-D treatment. Phytoinhibitory effects decreased under fungal
      infection and aphid feeding. Volatiles from A. conyzoides plants infected with E.
      cichoracearum or exposed to A. gossypii feeding inhibited or killed fungi and
      insects. Precocenes and their derivatives, monoterpenes, and sesquiterpenes were
      the major volatile components of A. conyzoides.

PMID- 12184396
TI  - Microbe inhibition by Tribolium flour beetles varies with beetle species, strain,
      sex, and microbe group.
AB  - Tribolium flour beetles produce defensive compounds, including quinones,
      putatively aimed at deterring predators and inhibiting microbes. Here we examine
      how effective the defensive secretions of Tribolium confusum and T. castaneum are
      at inhibiting growth of various microbes and how this varies with species,
      geographic strain, and sex of the beetles. We explore differences at both the
      kingdom and species level of common flour microbes in their susceptibility to
      defensive compounds. Beetle species and strains vary in their ability to inhibit
      microbial growth. In addition, microbes vary in their sensitivity to the beetles'
      defense compounds. The capability to suppress microbial growth is likely under
      stabilizing selection with optimum quinone production varying among populations
      and may be dependent on several environmental factors including temperature,
      humidity, and predators.

PMID- 12184397
TI  - Parthenogenesis, calling behavior, and insect-released volatiles of leafminer
      moth Phyllonorycter emberizaepenella.
AB  - We proved that the leafminer moth Phyllonorycter emberizaepenella (Lepidoptera:
      Gracillariidae) reproduces by parthenogenesis of the thelytoky type. Despite a
      complete absence of males, parthenogenetically reproducing females diurnally
      demonstrated the calling posture normally used for releasing signaling compounds.
      Two compounds, which we collected from a calling female, were identified as
      potential sex pheromone components: (8E, 10E)-8,10-tetradecadienyl acetate and
      (8E,10E)-8,10-tetradecadienol, the latter occurring only in trace amounts. In
      field experiments, no males were attracted to traps baited with either the
      potential sex pheromone or with virgin females. Both the pattern of behavior and
      the chemical characteristics of the pheromone of Ph. emberizaepenella species
      were similar to those known for Lepidoptera with the usual amphimictic mode of
      reproduction. Theoretical speculations that in thelytoky, where there is no need
      to find a sexual partner, the individuals would obtain certain advantages due to
      reduction in their sexual behavior, were, thus, not confirmed for Ph.
      emberizaepenella.

PMID- 12184398
TI  - Host-recognizing kairomones for parasitic wasp, Anisopteromalus calandrae, from
      larvae of azuki bean weevil, Callosobruchus chinensis.
AB  - Host-recognizing kairomones for the stinging behavior of the parasitic wasp,
      Anisopteromalus calandrae, were identified on host azuki bean weevil larvae,
      Callosobruchus chinensis (L.). The kairomones were extracted with acetone from
      Chinese green beans, from which emerged wasps and host weevils had been removed.
      The kairomones are a mixture of triacylglycerols and fatty acids, each of which
      is separately active, and with no observable synergistic effect between them.
      These compounds are known to be constituents of an oviposition-marking pheromone
      of host azuki bean weevils. However, they differ from the previously reported
      saturated hydrocarbons and diacylglycerols of the kairomone that another
      parasitic wasp, Dinarmus basalis, uses for the host recognition of C. chinensis.
      Thus, A. calandrae and D. basalis selectively utilize different constituents of
      the oviposition-marking pheromone of C. chinensis as host-recognizing kairomones.

PMID- 12184399
TI  - Cuticular hydrocarbon profiles of dominant versus subordinate male Nauphoeta
      cinerea cockroaches.
AB  - Interactions between male Nauphoeta cinerea cockroaches are characterized by an
      elaborate ritual that leads to a stable dominant-subordinate hierarchy between
      two individuals. Chemical signals involving volatile sex pheromones and cuticular
      hydrocarbons play an important role in establishing and maintaining dominance
      status. The present study was performed to identify cuticular hydrocarbons in two
      and three-times dominant or subordinate individuals obtained by forcing dyadic
      encounters. Two methods, i.e., solid-phase microextraction (SPME) and organic
      solvent extraction, were used to isolate cuticular hydrocarbons. A total of 23
      peaks of cuticular hydrocarbons were identified. Analysis showed quantitative
      differences in hydrocarbon profiles of three-times dominant and subordinate
      individuals according to extraction method and dominance status. Dominant
      individuals were characterized by higher proportions of the monomethylalkanes 11-
      and 13-MeC36, 13- and 15-MeC38, and 11-, 13-, and 15-MeC35, while subordinate
      individuals had higher proportions of the following monomethylalkanes: 7-, 9-.
      and 11-MeC31, 5-MeC31, 3- and 8-MeC32, and 9-, 10-, 11-, and 12-MeC32. Discussion
      focuses on the reliability of hydrocarbons as indicators of dominance status and
      on their correlation with physiological processes.

PMID- 12184400
TI  - Syntheses of female sex pheromone precursors of pine sawfly species and of some
      structurally related methyl-branched long-chain 2-alkanols.
AB  - 3,7-Dimethyl-2-undecanol, 3,7,9-trimethyl-2-tridecanol, and 3,7, 11-trimethyl-2
      tridecanol were synthesized as racemic mixtures in moderate yields. The alcohols
      are known precursors of the female sex pheromones of the pine sawfly species
      Diprion nipponica, Macrodiprion nemoralis, and Microdiprion pallipes,
      respectively. Stereoisomeric mixtures of 3,8,12-trimethyl-2-tridecanol, erythro
      (2R,3R, 11R/S)-3,11-dimethyl-2-tetradecanol, 3,5-dimethyl-2-tetradecanol, and 5,7
      dimethyl-2-tetradecanol, structurally related to sex pheromone alcohol precursors
      of pine sawfly species, were also synthesized in moderate yields. The key
      reaction in the syntheses was the ring opening of gamma-butyrolactones by using
      different alkyl lithiums as nucleophiles.

PMID- 12184401
TI  - Defining a synthetic pheromone blend attractive to male Heliothis subflexa under
      wind tunnel conditions.
AB  - Heliothis subflexa males were flown in a wind tunnel to a variety of combinations
      of synthetic pheromone components admixed (on a filter paper disk. Blends
      containing (Z)-l1-hexadecenal (Z11-16:Ald, 1000 ng), (Z)-9-hexadecenal (Z9
      16:Ald, 500 ng) and (Z)-11-hexadecenol (Z11-16:OH, 10-500 ng) elicited upwind
      flight and source contact in 52-69% of males. All these compounds have previously
      been isolated and identified from female H. subflexa gland extracts and volatile
      pheromone emissions. Males were not attracted by blends in which Z9-16:Ald was
      omitted (0% source contact). Similarly, blends lacking Z11-16:OH were
      unattractive to male H. subflexa (39% or less source contact). Males were
      extremely sensitive to the presence of Z11-16:OH; ever, responding in high
      numbers (57-69% source contact) to blends containing a dosage of 1% (10 ng) or
      greater Z11-16:OH. Males were unresponsive to blends in which Z9-16:Ald was
      replaced with a variety of dosages of (Z)-9tetradecenal, a secondary component of
      a closely-related congeneric species, Heliothis virescens. Another compound
      present in the blend emitted by con-specific females, (Z)-11-hexadecenyl acetate
      (Z11-16:Ac), did not inhibit H. subflexa males (69% source contact) when added to
      the three-component mixture (1:0.5:0.1) at a ratio of 0.1 (100 ng) with respect
      to Z11-16:Ald. These results indicate that Z9-16:Ald and Z11-16:OH are required
      in addition to Z11-16:Ald to elicit significant levels of upwind flight in H.
      subflexa males. The effects of Z11-16:Ac are more subtle, but at the dosage
      tested in these experiments, this compound does not have an antagonistic effect
      on upwind flight and source location by H. subflexa males.

PMID- 12184402
TI  - Variation in a female sexual attractiveness pheromone controls male mate choice
      in garter snakes.
AB  - Male red-sided garter snakes (Thamnophis sirtalis parietalis) display a courtship
      preference for larger females during the breeding season. Utilizing behavioral
      experiments and chemical analyses, we tested the hypothesis that males can
      discriminate among females of varying size solely by means of the sexual
      attractiveness pheromone, a previously characterized sex pheromone composed of a
      homologous series of long-chain saturated and omega-9 cis-unsaturated methyl
      ketones contained in the skin lipids of females. When presented with skin lipid
      extracts from large and small females, a greater proportion of males displayed
      courtship behaviors to large female extracts. This demonstrates that there is an
      intrinsic property of the female skin lipids that allows males to differentiate
      among large and small females. Analysis of the sexual attractiveness pheromone
      revealed that the necessary variation exists for this pheromone to function as a
      reliable indicator to males of female body size. Specifically, we observed a
      strong correlation between female snout-vent length and the relative
      concentration of saturated and omega-9 cis-unsaturated methyl ketones composing
      the pheromone; smaller females expressed pheromone profiles higher in saturated
      methyl ketones. while larger females expressed pheromone profiles dominated by
      unsaturated methyl ketones. The results of this study suggest that male red-sided
      garter snakes utilize compositional variation in the female sexual attractiveness
      pheromone to differentiate among potential mates of varying size.

PMID- 12184403
TI  - Volatile compounds in anal gland of Siberian weasels (Mustela sibirica) and
      steppe polecats (M. eversmanni).
AB  - The volatile constituents in anal gland secretions of two sympatric Mustela
      species, the Siberian weasel (M. sibirica) and steppe polecat (M. eversmanni),
      were studied by the headspace technique, followed by gas chromatography-mass
      spectrometry (GC-MS) analysis. Nine sulfur-containing compounds were identified.
      They were 2,2-dimethylthietane, (Z)- or (E)-2,4-dimethylthietane, (E)-2,3
      dimethylthietane, 2-ethylthietane, (E)-2-ethyl-3-methylthietane, (Z)-2-ethyl-3
      methylthietane, 2-propylthietane, 3,3-dimethyl-1,2-dithiacyclopentane, and (Z)
      3,4-dimethyl-2,2-dithiacyclopentane. Among them, (E)-2-ethyl-3- methylthietanes,
      (Z)-2-ethyl-3-methylthietanes, and (Z)-3,4-dimethyl-1,2-dithiacyclopentane were
      present in the polecat but not in the weasel. The predominant compound was 2,2
      dimethylthietane in the weasel and (E)- or (Z)-2,4-dimethylthietane in the
      polecat. These differences were consistent between the two species, regardless of
      sex and age and, therefore, could possibly be used for species recognition. In
      the weasel, 2-ethylthietane was found only in the female, and the relative
      abundance of several compounds was significantly different between males and
      females. In the polecat, although no sex-specific volatile compounds were found,
      males and females differed in the relative abundance of several of the compounds.
      In both species, the relative abundance of some compounds varied with age. We
      conclude that these volatile compounds can be used to communicate information
      about species, sex, and age.

PMID- 12184404
TI  - The local therapy for breast cancer as a model for evidence-based medical care.

PMID- 12184405
TI  - The promise and pitfalls of breast fluid proteins as markers for cancer
      detection.

PMID- 12184406
TI  - Curative treatment for advanced head and neck cancer in the community: has the
      time come?

PMID- 12184407
TI  - High-risk prostate cancer: how high is high?

PMID- 12184408
TI  - High basic fibroblast growth factor levels in nipple aspirate fluid are
      correlated with breast cancer.
AB  - PURPOSE: The angiogenic basic fibroblast growth factor (bFGF) and vascular
      endothelial growth factor are important in malignant breast epithelial growth.
      Nipple aspirate fluid (NAF) is a physiologic fluid collected noninvasively that
      contains proteins secreted by the breast ductal epithelium and may contain
      markers of breast cancer. The purpose of this study was to determine whether high
      concentrations of bFGF and vascular endothelial growth factor in NAF would be
      associated with in situ and invasive breast cancer, and whether prostate-specific
      antigen, a marker in NAF associated with breast cancer, would improve our ability
      to determine which subjects had the disease. METHODS: Both bivariate and
      multivariate analyses were performed to determine the effects of race, menopausal
      status, bFGF concentration, and prostate-specific antigen on cancer risk.
      Bivariate analysis was also performed to determine the relationship between
      vascular endothelial growth factor concentration and cancer risk. RESULTS: Mean
      NAF bFGF levels were higher in women with breast cancer than in those without
      (19.2 vs 1.74 ng/g). Vascular endothelial growth factor was not associated with
      breast cancer. Race and menopausal status did not significantly affect the
      relationship between bFGF and cancer risk. bFGF, race, and menopausal status were
      each independent predictors of breast cancer, with bFGF being the most important.
      With knowledge of all three variables, the model was 89.9% sensitive and 69.0%
      specific in predicting which women had breast cancer. Adding prostate-specific
      antigen increased the sensitivity to 90.9% and the specificity to 83.3%. In
      subjects with NAF bFGF > 150 ng/g and prostate-specific antigen < 100 ng/g, 94.1%
      (32/34) of subjects had cancer. For women with NAF prostate-specific antigen >
      100 ng/ g and bFGF < 150 ng/g, 90.5% were cancer free. CONCLUSIONS: bFGF
      concentration in NAF is directly associated with breast cancer, regardless of
      race and menopausal status. NAF bFGF may prove helpful in the early detection of
      breast cancer.

PMID- 12184409
TI  - Induction paclitaxel, carboplatin, and infusional 5-FU followed by concurrent
      radiation therapy and weekly paclitaxel/carboplatin in the treatment of locally
      advanced head and neck cancer: a phase II trial of the Minnie Pearl Cancer
      Research Network.
AB  - PURPOSE: The purpose of this study was to evaluate the feasibility, toxicity, and
      efficacy of a novel combined-modality treatment for patients with locally
      advanced squamous carcinoma of the head and neck. PATIENTS AND METHODS: In this
      multicenter, community-based phase 11 study, 123 previously untreated patients
      with locally advanced squamous carcinoma of the head and neck received 6 weeks of
      induction chemotherapy followed by concurrent high-dose radiation therapy and
      weekly chemotherapy. Induction chemotherapy included paclitaxel (200 mg/m2, 1
      hour i.v. infusion) on days 1 and 22, carboplatin (AUC 6.0 i.v.) on days 1 and
      22, and 5-fluorouracil (225 mg/m2 per day, 24-hour continuous i.v. infusion) on
      days 1-43. After 1 week without therapy, radiation therapy, 1.8 Gy/day, 5 days
      weekly, to a total dose of 68.4 Gy, was administered to the primary site and the
      bilateral cervical lymph nodes. During radiation therapy, patients also received
      six weekly doses of paclitaxel (50 mg/m2, 1-hour i.v. infusion) and carboplatin
      (AUC 1.0 i.v). After completion of therapy, patients were restaged with computed
      tomographic and endoscopic examination; patients in complete remission were
      followed up without further treatment. RESULTS: One hundred twenty-three patients
      (74% with stage IV disease) entered this trial, and 111 patients (90%) completed
      the entire treatment course. Seventy of 116 evaluable patients (60%; 95% Cl, 51%
      69%)had a clinical complete response to treatment. After a median follow-up of 24
      months, the 2-and 3-year actuarial survivals were 66% and 51%, respectively.
      Local toxicity was moderately severe during combined-modality therapy; however,
      xerostomia has been the only frequent chronic toxicity of this program.
      CONCLUSIONS: This novel combined-modality treatment program, containing
      paclitaxel and avoiding the use of cisplatin, is feasible, is highly active, and
      can be administered with acceptable toxicity in a community-based setting.
      Aggressive nutritional support should be considered in patients receiving this
      regimen, to improve acute palliation and to maximize the delivery of combined
      modality therapy. Further evaluation of this treatment program is warranted.
      Incorporation of various novel biologic agents, particularly the epidermal growth
      factor receptor antagonists, may further improve efficacy.

PMID- 12184410
TI  - Biochemical outcome for hormone-naive patients with high-risk prostate cancer
      managed with permanent interstitial brachytherapy and supplemental external-beam
      radiation.
AB  - PURPOSE: The purpose of this article is to report the 5-year biochemical disease
      free outcome for hormone-naive patients with high-risk disease who underwent
      permanent prostate brachytherapy. Multiple clinical and treatment parameters were
      also evaluated to determine whether any of these influence biochemical outcome.
      MATERIALS AND METHODS: Sixty-six hormone-naive patients underwent transperineal
      ultrasound-guided permanent prostate brachytherapy with generous periprostatic
      margins by use of either 103Pd or 125I for high-risk prostate cancer from April
      1995 to October 1999. High-risk patients presented with two or three of the
      following risk factors: Gleason score > or = 7, prostate-specific antigen > or =
      10 ng/mL, and clinical stage > or = T2b, 1997 AJCC. No patient underwent
      pathological lymph node staging. Only one patient was implanted with monotherapy,
      whereas 65 patients received supplemental external-beam radiation therapy before
      a prostate brachytherapy boost. The median patient age was 69 years (range, 50-81
      years). No patient was lost to follow-up. The mean follow-up and median follow-up
      were 53.2 +/- 14.9 months and 53.7 months, respectively (range, 19.8-79.7
      months). Follow-up was calculated from the day of implantation. Biochemical
      disease-free survival was defined by the American Society of Therapeutic
      Radiology and Oncology consensus definition. Clinical parameters evaluated for
      biochemical disease-free survival included patient age, clinical stage, Gleason
      score, and pretreatment prostate-specific antigen. Treatment parameters included
      use of supplemental external-beam radiation therapy and choice of isotope.
      RESULTS: The 5-year actuarial biochemical disease-free survival rate was 79.9%.
      In multivariate analysis, preimplantation prostate-specific antigen (P = 0.008)
      was the only clinical or treatment parameter that predicted for biochemical
      failure. The mean and median posttreatment prostate-specific antigen levels were
      0.13 +/- 0.22 ng/mL and < 0.1 ng/mL, respectively. DISCUSSION: At a median follow
      up of 53.7 months, hormone-naive patients with high-risk disease who undergo
      permanent prostate brachytherapy have a high probability of 5-year biochemical
      disease-free survival and an apparent plateau on the biochemical disease-free
      survival curve.

PMID- 12184411
TI  - The K252a derivatives, inhibitors for the PAK/MLK kinase family selectively block
      the growth of RAS transformants.
AB  - BACKGROUND: Oncogenic RAS mutants such as v-Ha-RAS activate members of Rac/CDC42
      dependent kinases (PAKs) and appear to contribute to the development of more than
      30% of all human cancers. PAK1 activation is essential for oncogenic RAS
      transformation, and several chemical compounds that inhibit Tyr kinases essential
      for the RAS-induced activation of PAK1 strongly suppress RAS transformation
      either in cell culture or in vivo (nude mice). Although we have developed a cell
      permeable PAK-specific peptide inhibitor called WR-PA18, so far no chemical
      (metabolically stable) compound has been developed that directly inhibits PAK1 in
      a highly selective manner. Thus, we have explored such a PAK1 inhibitor(s) among
      synthetic derivatives of an adenosine triphosphate antagonist. RESULTS: From the
      naturally occurring adenosine triphosphate antagonist K252a, we have developed
      two bulky derivatives, called CEP-1347 and KT D606 (a K252a dimer), which
      selectively inhibit PAKs or mixed-lineage kinases both in vitro and in cell
      culture and convert v-Ha-RAS-transformed NIH 3T3 cells to flat fibroblasts
      similar to the parental normal cells. Furthermore, these two K252a analogues
      suppress the proliferation of v-Ha-RAS transformants, but not the normal cells.
      CONCLUSION: These bulky adenosine triphosphate antagonists derived from K252a or
      related indolocarbazole compounds such as staurosporine would be potentially
      useful for the treatment of RAS/ PAK1-induced cancers, once their anti-PAK1
      activity is significantly potentiated by a few additional chemical modifications
      at the sugar ring suggested in this paper.

PMID- 12184412
TI  - Implementation and results of a test dose program with taxanes.
AB  - PURPOSE: A pilot taxane test-dose policy was developed and implemented to
      determine whether the severity of patient hypersensitivity reaction and drug
      waste would be reduced. PATIENTS AND METHODS: Data from 206 eligible cancer
      patients undergoing first-dose taxane chemotherapy were analyzed. The severity of
      hypersensitivity reactions before and after the implementation of taxane test
      dose was graded (scale 1-4) and analyzed for statistical differences between
      groups. Average drug wastage was calculated before and after program initiation.
      RESULTS: Twenty-two of 206 patients (10.7%) experienced a hypersensitivity
      reaction. The mean hypersensitivity reaction severity for reacting patients who
      did not receive a test dose (N = 12) was 3.3, and for those who were given a test
      dose (N = 10), it was 1.5. Only one of five patients who experienced a
      hypersensitivity reaction that required hospitalization was from the test-dose
      group. The value of drug alone wasted before test-dose utilization was about
      $1794 per reacting patient, and the use of taxane test doses saved approximately
      $1784 per reacting individual. This represented more than a $178 savings for
      every patient receiving a taxane for the first time. These figures do not include
      resuscitation, hospital, and other subsequent other costs associated with
      morbidity. CONCLUSIONS: Implementation of a taxane test-dose policy significantly
      reduced hypersensitivity reaction severity, drug wastage, and hospitalizations.

PMID- 12184413
TI  - Isolated pulmonary recurrence after resection of colorectal hepatic metastases-
      is resection indicated?
AB  - BACKGROUND: Resection of colorectal hepatic metastases is an accepted treatment
      modality for stage IV colorectal cancer. Concurrent or sequential pulmonary
      metastasectomy continues to be a controversial strategy. We analyzed factors that
      predicted pulmonary recurrence in patients with resected hepatic metastases and
      examined the efficacy of these combined interventions in the treatment of
      metastatic colorectal cancer. METHODS: A retrospective review of a database of
      patients who underwent resection of colorectal hepatic metastases was performed
      to identify patients who either had synchronous pulmonary metastases (defined as
      pulmonary recurrence at the time of or within 3 months of hepatic metastasectomy)
      or subsequently experienced pulmonary metastases. Patient demographics, operative
      interventions, and overall survival were analyzed. Statistical methods included
      unpaired Student's t-test, actuarial survival and log-rank analysis. RESULTS:
      Twenty-one patients (19%) had pulmonary metastases after hepatic resection, of
      which 12/21(57%) underwent pulmonary resection. No differences were observed
      between the resection group, the nine patients with pulmonary metastases who did
      not undergo resection, and the 87 patients without pulmonary metastases with
      regard to age, sex, race, or extent of hepatic metastases. When comparing the
      resected versus the unresected pulmonary recurrences, the disease-free interval
      from hepatic resection to detection of pulmonary metastases was 21 +/- 20 months
      (range, 3-72 months) versus 16 +/- 8 months (range, 4-25 months), respectively.
      All patients with pulmonary recurrence who underwent pulmonary metastasectomy had
      unilateral disease. Seven of 12 (58%) underwent wedge/segmental resections, and
      the remaining five (42%) required lobectomy in order to obtain a complete
      resection. Four patients who underwent pulmonary resection had multiple lung
      metastases (two to four lesions), and eight had isolated metastasis. There were
      no perioperative deaths in the pulmonary metastasectomy group. Contraindications
      to pulmonary resection included extensive pulmonary disease and concurrent
      extrapulmonary disease. A survival benefit was noted at 3 years for the resected
      versus the unresected group (60% vs 31%). Survival was no different between the
      resected pulmonary recurrence patients and the resected hepatic metastases only
      patients (60% vs 54%). CONCLUSIONS: Pulmonary metastasectomy can be performed
      safely and effectively in patients with recurrent disease after hepatic resection
      for colorectal metastases. Prolonged survival can be achieved with resection of
      isolated pulmonary recurrence after hepatic resection for colorectal cancer.
      Further studies that delineate selection criteria for pulmonary resection of
      colorectal metastases are warranted.

PMID- 12184414
TI  - Electrolyte abnormalities with zoledronic acid therapy.

PMID- 12184415
TI  - Differential scanning calorimetric studies of nickel titanium rotary endodontic
      instruments.
AB  - Differential scanning calorimetric (DSC) analyses were performed between -130
      degrees and 100 degrees C on specimens prepared from nickel-titanium (NiTi)
      rotary endodontic instruments: ProFile (n = 5), Lightspeed (n = 4), and Quantec
      (n = 3). The ProFile and Lightspeed instruments were in the as-received
      condition, whereas the Quantec instruments were randomly selected from a dental
      clinic and had unknown history. The DSC plots showed that the ProFile and
      Lightspeed instruments analyzed had the superelastic NiTi property, with an
      austenite-finish (Af) temperature of approximately 25 degrees C. Differences in
      DSC plots for the ProFile instruments and the starting wire blanks (n = 2) were
      attributed to the manufacturing process. The phase transformation behavior when
      the specimens were heated and cooled between -130 degrees and 100 degrees C, the
      temperature ranges for the phase transformations, and the resulting enthalpy
      changes were similar to those previously reported for nickel-titanium orthodontic
      wires having superelastic characteristics or shape memory behavior in the oral
      environment. The experiments demonstrated that DSC is a powerful tool for
      materials characterization of these rotary instruments, providing direct
      information not readily available from other analytical techniques about the NiTi
      phases present, which are fundamentally responsible for their clinical behavior.

PMID- 12184416
TI  - Microleakage of resected MTA.
AB  - Forty-six single rooted extracted human teeth were used in this study. After
      cleaning and shaping, twenty canals were randomly selected for obturation with
      MTA placed in an orthograde manor (Group 1). Another twenty roots were obturated
      with gutta-percha and Kerr EWT sealer, using warm vertical compaction (Group 2).
      The apical 3 mm of each root in both groups were resected at approximately 45
      degrees to its long axis. The teeth were aged for 48 h in a humidor. The root
      ends of the teeth in Group 2 were then prepared and received MTA as a root-end
      filling material to a depth of 3 mm. Six roots were used as positive and negative
      controls. The roots of all teeth were placed in contact with India ink for 48 h.
      The roots were split and examined for dye leakage. There was no discernible
      leakage in teeth with resected MTA or those with MTA placed as a retrograde root
      end filling material. We found no significant difference in dye leakage between
      resected MTA (Group 1) and non-resected MTA (Group 2). Based on these results it
      appears that the resection of set MTA does not affect its sealing ability.

PMID- 12184417
TI  - The effect of sodium hypochlorite irrigant concentration on tooth surface strain.
AB  - The effect of root-canal irrigation with different concentrations of sodium
      hypochlorite (3%, 5.1%, 7.3% NaOCI) on the mechanical properties of teeth was
      investigated in vitro. Root canals of 13 extracted, human premolars, denuded of
      enamel, were prepared with nickel-titanium rotary instruments (Quantec) to a
      standard size by using saline irrigation. An electrical strain gauge was bonded
      to the cervical aspect of each tooth. The 10 experimental teeth were subjected to
      5 successive, 30-minute periods of irrigation. The irrigants were used in the
      following order: (a) saline; (b) 3.0% NaOCI; (c) 5.1% NaOCI; (d) 7.3% NaOCI; (e)
      saline. Three control teeth were irrigated with saline only for all five periods.
      After each irrigation, the teeth were cyclically loaded to 110N while the surface
      strain was measured. Changes in strain of the test teeth after each irrigation
      regimen followed broadly similar patterns that were different from the control
      teeth. There was no difference, however, in the strain recorded after irrigation
      by the different irrigants within the experimental group.

PMID- 12184418
TI  - Efficiency of hand and rotary instruments in shaping oval root canals.
AB  - This study was designed to determine the efficiency of hand and rotary
      instruments in shaping oval root canals. Seventy-five oval canals were equally
      divided into three groups. The apical third was prepared with rotary LightSpeed
      instruments either to size 52.5 (mandibular incisors) or to size 57.5 (distal
      root of mandibular molars). The middle third with an oval cross-section was
      shaped with Hedstrom hand files using circumferential technique, with 6% taper
      rotary Hero files in a circumferential filing movement or with rotary LightSpeed
      instruments in a step-back technique. Instrumentation was performed under
      clinical conditions in a phantom head. The teeth were sectioned at two levels in
      the middle third of the root. An assembly technique allowed comparing the canal
      outline before and after instrumentation. The photographed root sections were
      superimposed and traced under a stereomicroscope. The ratio of prepared to
      unprepared canal outline was calculated for each section. The lowest values were
      observed in the LightSpeed group (mean: 0.42; 95% confidence interval (CI): 0.37;
      0.47). Significantly higher values were recorded in the Hero group (mean: 0.58;
      95% CI: 0.53; 0.64) and in the Hedstrom group (mean: 0.56; 95% CI: 0.49; 0.62).
      No instrumentation technique was capable of completely preparing dentin walls of
      oval root canals. Circumferential filing of the middle third of oval root canals
      with either 6% taper Hero files or conventional Hedstrom hand files gave
      comparable results.

PMID- 12184419
TI  - Effect of drainage upon access on postoperative endodontic pain and swelling in
      symptomatic necrotic teeth.
AB  - The purpose of this retrospective study was to determine the effect of drainage
      upon access on postoperative endodontic pain and swelling in symptomatic necrotic
      teeth. One hundred twenty-four emergency patients participated and each had a
      clinical diagnosis of a symptomatic necrotic tooth with an associated periapical
      radiolucency. The occurrence of drainage upon access was timed and recorded.
      After endodontic treatment, patients received ibuprofen, acetaminophen with
      codeine (30 mg), and a 6-day diary to record pain, percussion pain, swelling, and
      number and type of pain medication taken. The majority of patients with
      symptomatic necrotic teeth had significant postoperative pain and required
      analgesic medication to manage this pain. Obtaining short-term drainage upon
      access (average of 1.85 min) did not significantly (p > 0.05) reduce pain,
      percussion pain, swelling, or the number of analgesic medications taken for
      symptomatic necrotic teeth with periapical radiolucencies.

PMID- 12184420
TI  - An observation of the healing process of periapical lesions by digital
      subtraction radiography.
AB  - The purpose of this study was to evaluate the efficacy of digital subtraction
      radiography using a direct digital imaging system in the follow-up study of
      endodontically treated teeth. The RVG-S was used as a direct digital imaging
      system. The intraimage variation of the original RVG-S image caused by dark
      current and sensitivity variations among pixels was corrected by pixel-to-pixel.
      The interimage variation was further corrected using a copper step-wedge attached
      to the sensor. Standardized images were obtained from the same geometrical setup
      during the follow-up. Pixel values at the regions of interest positioned on the
      periapical lesion increased after the endodontic treatment, and this change
      continued during the observation period up to 545 days. The subtraction method
      with direct digital radiography will be a useful tool to evaluate the healing
      process in endodontic treatments.

PMID- 12184422
TI  - The influence of sodium hypochlorite irrigation on the accuracy of the Root ZX
      electronic apex locator.
AB  - The purpose of this in vitro investigation was to determine whether the presence
      of sodium hypochlorite influences the accuracy of the Root ZX electronic apex
      locator. Forty, extracted, human teeth were mounted in an experimental apparatus.
      After achieving ideal access, working length measurements were obtained using the
      Root ZX. The canals were flushed with 2.125% sodium hypochlorite and measurements
      were again made with the electronic apex locator. Before measuring a third time,
      5.25% sodium hypochlorite was then administered to each canal. Finally, the tooth
      was removed from the apparatus and the actual canal length was determined by
      measuring a file brought to the apical constriction (verified by direct
      visualization). No significant differences were found between the experimental
      groups. Overall, Root ZX measurements were within 0.5 mm of the actual length 83%
      of the time. The results of this study indicate that the Root ZX is not adversely
      affected by the presence of sodium hypochlorite.

PMID- 12184421
TI  - A survey of endodontic residents' attitudes about a career in dental education.
AB  - There is an increasing demand for qualified educators throughout American dental
      schools. A survey designed to identify reasons for interest or lack of interest
      in education as a career was sent to all first and second year endodontic
      residents enrolled in the United States in 1999. Seventy-four percent of the 392
      students responded (224 men and 65 women). The survey results were analyzed using
      descriptive statistics and Chi-square tests. Ninety-three percent of the
      respondents reported an interest in teaching on a part time basis, and of those,
      51% were willing to teach 1.5 days/week, but only 16% were willing to teach more
      than 1.5 days/week. The survey included a list of eight potential reasons for not
      being interested in a career in education and respondents were asked to mark
      their top three. Low salaries for teachers was the most frequently chosen reason
      (70%), 51% listed educational debt, and 31% listed desire to be their own boss or
      lack of interest in research. Students were also asked to choose the top three
      reasons for interest in dental education from a list of seven reasons. Enjoyment
      of clinical teaching was the most frequently selected reason (41%): 32% included
      enjoying working with others in the field and 24% listed enjoyment of the
      university atmosphere.

PMID- 12184423
TI  - Virtual endodontics: three-dimensional tooth volume representations and their
      pulp cavity access.
AB  - The purpose of this study was the application of both digital three-dimensional
      image processing and virtual reality techniques in endodontics. Three-dimensional
      volume representations of 2 teeth from each tooth category, 16 teeth in total,
      have been reconstructed. All teeth were embedded in polyester resin, and serial
      cross-sections 0.75-mm thick were taken from each tooth by using a special
      microtome. Each section was studied under a stereoscopic microscope, and its
      microscopic image was directly digitized using a video-camera. The surfaces of
      hard dental tissues were segmented from each section. Semiautomatic alignment and
      frame interpolation were performed on the sequence of tooth sections by using
      appropriate digital image processing techniques. Three-dimensional volume
      representations from each tooth were achieved in this project to produce the
      final three-dimensional teeth models, on which virtual accesses of pulp cavities
      have been performed. Three-dimensional teeth volume representations and virtual
      tooth "drilling" could serve as perfect educational tools under certain
      circumstances.

PMID- 12184424
TI  - Antimicrobial efficacy of various root canal preparation techniques: an in vitro
      comparative study.
AB  - In this study, we compared the antimicrobial efficacy of various root canal
      preparation techniques and instruments in the root canals of 40 human first
      maxillary premolars extracted for orthodontic reasons. After extirpation of the
      pulp, teeth were sterilized in an autoclave. Then, the root canals were infected
      with Enterococcus faecalis suspension and the teeth incubated at 37 degrees C for
      24 h. Thereafter, the teeth were divided into five groups: preparation with K
      file or K-Nitiflex file (step-back technique; groups 1 and 2), K-reamer
      (standardization technique; group 3), irrigation only (group 4), and no treatment
      (group 5). Before and after treatments, samples were taken for culture. Results
      were evaluated after 24-h incubation in E67 selective culture medium. We observed
      a considerable reduction in bacterial population after mechanical preparation. No
      significant differences were seen among the efficacy of the various preparation
      techniques and files used.

PMID- 12184425
TI  - The effect of two different root canal sealers and smear layer on resistance to
      root fracture.
AB  - The purpose of this in vitro study was to test the effect of Ketac-Endo (KE) and
      AH 26 on resistance to root fracture and also to evaluate the effect of smear
      layer. Seventy-two human maxillary canine teeth were randomly divided into six
      groups (n = 12) and were prepared using six different methods: group 1: KE,
      without smear layer (smear -); group 2: KE, with smear layer (smear +); group 3:
      AH 26, smear (-); group 4: AH 26, smear (+); group 5 (negative control):
      nonprepared; group 6 (positive control): prepared but unfilled. After storing 1
      week in 100% humidity at 37 degrees C, the coronal lingual walls and root canal
      spaces were lowered 2 mm below the buccal walls of the roots. The samples were
      placed into acrylic resin blocks so that 10 mm of buccal roots were exposed and
      were placed in a specially designed steel pad at an angle of 15 degrees to the
      long axis of the root. A slowly increasing force was applied at the junction of
      the buccal wall and root canal space until fracture occurred. The force required
      to fracture each tooth was recorded as kg and statistically analyzed using one
      way analysis of variance and Duncan tests. The results indicated that
      instrumentation of the root canals significantly weakened the tooth structure to
      fracture (p < 0.05). The canals obturated with either sealer were significantly
      stronger than roots whose canals were instrumented but not obturated (p < 0.05),
      and there was no difference between the sealers. The presence or absence of the
      smear layer did not cause any significant effect on the root fracture resistance
      of the teeth (p > 0.05).

PMID- 12184426
TI  - Scanning electron microscopic investigation of the surface of fiber posts after
      cutting.
AB  - This study evaluated the surface of different types of fiber posts after cutting
      and investigated whether different cutting procedures can affect the integrity of
      the posts. Six types of fiber posts were selected for this study (Carbon Fiber
      Posts, Quartz Fiber Posts, Aesthetic Posts, Aesthetic Plus Posts, Translucent
      Posts, Dentatus, FRC Postec Posts). Fifteen posts of each type were studied. All
      posts had a diameter of 1.2 to 1.4 mm and were between 14 and 16 mm long. Each
      group was divided into three subgroups (n = 5) according to cutting method:
      diamond bur, carborundum disk, or scissors. The samples were then processed for
      scanning electron microscopic investigation. At low magnifications, no
      microscopic differences were found among the samples of groups 1-4 and 6.
      Surfaces from group 5 were more irregular, but only when cut using rotating
      instruments. All groups showed differences between surfaces cut with scissors and
      those cut with either diamond bur or carborundum disk. Posts displayed regular
      surfaces after cutting with a diamond bur. Cutting with a carborundum disk
      produced a mostly regular surface but sometimes produced irregularities close to
      the surface borders. The surfaces cut with scissors showed two plane and
      convergent flanges, and because of the formation of fracture lines these posts
      lost their integrity not only at the cutting surface but also along their length.
      The results of this study indicated that fiber posts can be cut using a diamond
      bur mounted in a handpiece under copious water coolant. Although the carborundum
      disk cutting procedure showed a less regular post surface, it can be speculated
      that it might be clinically acceptable. The cutting procedure using scissors
      should be avoided.

PMID- 12184427
TI  - Course of infection and case outcome in individuals diagnosed with microbial
      colonies morphologically consistent with Actinomyces species.
AB  - Actinomycosis is considered to be a rare disease in the oral region. A
      retrospective study of files of the University of Nebraska Medical Center College
      of Dentistry, Department of Pathology, revealed 30 cases in which Actinomyces
      species were detected from the years 1982 to 2001 (28,490 specimens). Biopsy
      submission forms and patient records were reviewed in each of these cases with
      particular attention to clinical impression, subsequent treatment, and case
      outcome. Classic treatment for actinomycosis involves the excision of the
      affected area as well as long-term antibiotics. Our study indicates that
      antibiotics may not be necessary in treatment of the localized dental
      presentation of actinomycosis.

PMID- 12184428
TI  - Options for blocking interleukin-1 in patients with rheumatoid arthritis.

PMID- 12184429
TI  - Ferritin levels in adult Still's disease: any sugar?

PMID- 12184430
TI  - Whiplash: myth or reality?

PMID- 12184431
TI  - Current and potential treatments for primary Sjogren's syndrome.
AB  - A precise definition of primary Sjogren's syndrome resting on 'revised' or
      'international' criteria has been accepted by most experts. This is important
      because the symptoms of primary Sjogren's syndrome, namely, dryness, fatigue, and
      pain, are common in the population at large and can occur in the absence of
      autoimmune disease as a result of medication use, anxiety and depression, or
      normal aging. This widely accepted definition is particularly valuable as a tool
      for obtaining homogenous patient populations for trials of new therapeutic
      agents. In this review article, before discussing treatments for complications
      and current hopes about second-line drugs, we present an update on available
      treatments forthe symptomatic triad (dryness, fatigue, and diffuse pain) seen in
      autoimmune Sjogren's syndrome and in some cases of isolated sicca syndrome. These
      very bothersome and permanent symptoms have a negative effect on quality of life.
      The most recent data show that systemic cholinergic agonists (pilocarpine and
      cevimiline) are effective in the symptomatic treatment of dryness, that
      cyclosporine eye drops may relieve ocular symptoms, and that TNFalpha inhibitors
      may find a new indication in Sjogren's syndrome.

PMID- 12184432
TI  - Role for vascular investigations in giant cell arteritis.
AB  - Giant cell arteritis is characterized by diffuse arterial inflammation that
      selectively involves the superficial temporal arteries but can occur in larger
      arteries. Various vascular investigations can assist in diagnosing and evaluating
      the extent of giant cell arteritis. Imaging techniques, mainly Doppler
      ultrasonography of the superficial temporal arteries, seem less reliable for the
      diagnosis than temporal artery biopsy, which is safe and remains indispensable.
      Investigations of larger arteries can detect asymptomatic stenotic lesions, which
      are common, particularly in the axillary and subclavian arteries. Involvement of
      the aorta can cause life-threatening dissection or aneurysmal rupture. Imaging
      techniques useful for diagnosing aortic involvement include ultrasonography,
      computed tomography, magnetic resonance imaging, and aortography. Although there
      is no standardized strategy for aortic lesion detection, helical computed
      tomography may be valuable.

PMID- 12184433
TI  - Bone involvement in patients with chronic cholestasis.
AB  - Osteopenia is a classic complication of chronic cholestasis related to primary
      biliary cirrhosis or primary sclerosing cholangitis. Most studies were done in
      patients with primary biliary cirrhosis, which is by far the more common of the
      two diseases. Estrogen deficiency may be the main cause of bone loss in these
      patients, most of whom are perimenopausal women. Liver disease severity does not
      seem to play a major role, although a high bone turnover rate is seen in some
      patients before the menopause. The fracture risk has not been accurately
      evaluated, and the limited data on management indicate that hormone replacement
      therapy is effective and safe, whereas bisphosphonates have not been proven
      effective. Primary sclerosing cholangitis is rare and, consequently, few data are
      available. Males are predominantly affected. Concomitant inflammatory bowel
      disease and glucocorticoid therapy are the main causes of bone loss in primary
      sclerosing cholangitis.

PMID- 12184434
TI  - Effect of cryoglobulin and crystalcryoglobulin on TNF-alpha production by normal
      human monocytes.
AB  - OBJECTIVES: We recovered an IgG1-kappa cryocrystalglobulin in synovial fluid and
      membrane specimens from a patient with destructive arthropathy. In the present
      study, we investigated its proinflammatory properties by measuring its effects on
      TNF-alpha production by normal human monocytes. MATERIALS AND METHODS: Normal
      human monocytes isolated by plastic adhesion were cultured in microtiter plates.
      Adherent monocytes were cultured for 6, 8, and 24 hours with sterile
      cryocrystalglobulin (150 microg/mL and 2 mg/mL), type I noncrystallised
      cryoglobulin (same concentrations), monosodium urate (MSU) crystals (2 mg/mL),
      LPS (10 microg/mL), or medium alone. Supernatant TNF-a concentrations were
      assayed using an ELISA. RESULTS: Cryocrystalglobulin had no effect on TNF-alpha
      production by normal human monocytes. Noncrystallised cryoglobulin increased TNF
      alpha levels in supernatants in a time-dependent and concentration-dependent
      fashion. This increase was significantly less marked than the increases achieved
      with MSU crystals or LPS. CONCLUSION: IgG1kappa cryocrystalglobulin has no effect
      on TNF-alpha production by normal human monocytes. Fc region changes within the
      cryocrystalglobulin molecule may explain this finding.

PMID- 12184435
TI  - Is the relationship between spondyloarthropathy and Sjogren's syndrome in women
      coincidental? A study of 13 cases.
AB  - OBJECTIVE: To determine the prevalence of Sjogren's syndrome (SS) in women with
      spondyloarthropathy (SpA). METHODS: Forty-one women with SpA manifesting as
      inflammatory back pain and/or peripheral arthritis were diagnosed as having
      ankylosing spondylitis, undifferentiated spondyloarthropathy, psoriatic
      arthritis, or enteropathic arthropathy based on accepted criteria. A validated
      questionnaire was used to look for sicca symptoms in the SpA group and in 102
      controls with degenerative rheumatic diseases. Women with SpA and sicca symptoms
      and/or positive antinuclear antibodies (ANA) were investigated for SS by minor
      salivary gland biopsy. In the SpA group, the following tests were done: HLA B27;
      HLA DR, DQ; ENA; and serology for CMV, EBV, HIV, hepatitis B, and hepatitis C.
      RESULTS: Thirteen women (31.7%) met European criteria for SS, compared to three
      (2.9%) of the controls. Of the 41 women with SpA, 16 (39%) were ANA-positive. ANA
      were detected in eight of the 16 (50%) patients with SS. HLA B27 was present in
      11 of the 13 (84.6%) SS patients. HLA DR 04.04 and DQ 03.03 seemed more common in
      SS patients, but the difference was not statistically significant. CONCLUSION: SS
      was far more common in the women with SpA (31.7%) than in the controls (2.9%),
      suggesting that the SpA-SS association may not be coincidental.

PMID- 12184437
TI  - Pamidronate treatment in SAPHO syndrome.
AB  - OBJECTIVE: Pamidronate is usually administered because of its antiosteoclastic
      effects but seems to have anti-inflammatory properties also. SAPHO syndrome is
      characterized by both increased bone remodeling and inflammatory osteitis,
      indicating that it may respond favorably to pamidronate's dual mechanism of
      action. PATIENTS AND METHODS: We report five cases of SAPHO syndrome refractory
      to standard treatments. All patients were taking nonsteroidal anti-inflammatory
      drugs, either alone or in combination with analgesics, glucocorticoids, and/or
      second-line drugs. We used intravenous pamidronate during exacerbations of the
      disease. The primary evaluation criterion was the reduction in the visual analog
      scale (VAS) score for pain, and a response was defined as a greater than 50%
      reduction. RESULTS: Four of the five patients had a response after 1 week. Two of
      these four patients still met the response criterion after 3 months. Four of the
      five patients were able to reduce the dosage of their usual medications. In one
      patient, pamidronate therapy was associated with an increase in the intervals
      between exacerbations. Joint Bone

PMID- 12184436
TI  - Hip osteoarthritis: short-term efficacy and safety of viscosupplementation by
      hylan G-F 20. An open-label study in 22 patients.
AB  - We studied the short-term safety and efficacy of intraarticular hylan G-F 20
      (Synvisc) in patients with symptomatic hip osteoarthritis. METHODS: In this open
      label prospective study, patients who had hip osteoarthritis with a visual analog
      pain scale score greaterthan 40/100 and a Lequesne index greater than 6 received
      one or two intra-articular injections of hylan G-F 20 under fluoroscopic
      guidance. The patients were evaluated once a month. A response was defined as a
      50% decrease in the Lequesne score after 1 month as compared to baseline.
      RESULTS: Thirty injections were performed in 22 patients with a mean age of 54
      years. The response rate was 50% (11/22) after the first injection. Five of the
      11 patients who failed to respond to the first injection received a second
      injection on day 30; two had a response, yielding a cumulative response rate of
      13/22. In the six patients followed up for more than 6 months, the improvement
      was sustained. Short-term safety was satisfactory, with a self-limited
      exacerbation of pain during the first few days in three patients but no
      infections or other side effects.

PMID- 12184438
TI  - Validity of the French-language version of the Quebec back pain disability scale
      in low back pain patients in France.
AB  - OBJECTIVES: The primary objectives were to evaluate the acceptability in France
      of the Quebec Back Pain Disability Scale (QBPDS) in its original French-language
      version and to study its correlational validity against indicators of impairment,
      pain, disability, psychological status, and perceived health status. MATERIAL AND
      METHODS: Thirty-two patients with chronic low back pain were recruited at the
      rheumatology outpatient clinic of a French hospital. A physical examination was
      performed for determination of an impairment score, and scales were completed for
      pain (visual analog scale and Saint-Antoine Questionnaire), disability (QBPDS and
      Dallas Scale [DS]), perceived health status (Nottingham Health Profile, NHP), and
      psychological status (Hospital Anxiety and Depression Scale, HADS). RESULTS:
      Acceptability, internal consistency, and content validity of the QBPDS were
      satisfactory. Investigation of correlational validity showed good agreement with
      the DPQ (r = 0.755) and NHP (r = 0.739) and fair agreement with the impairment
      score (r = 0.449), the VAS pain score (r = 0.448), and the HADS score (r =
      0.473). The QBPDS showed good discriminating power. Validity of the QBPDS was
      confirmed. DISCUSSION: Our results confirm the good measurement properties of the
      original French-language version of the QBPDS in French hospital-clinic patients
      with chronic low back pain. Comparison of the QBPDS and DPQ in this study shows
      that the QBPDS is better for evaluating disability, whereas the DPQ evaluates the
      overall, functional, psychological, and social impact of low back pain.

PMID- 12184440
TI  - Lead-related gout. A case report.
AB  - Gout secondary to lead-induced nephropathy is a long-term complication of
      occupational lead exposure. We report a case of this now-rare condition. The
      patient was a 63-year-old man who had been a miner from 1950 to 1970. Thirty
      years after cessation of his exposure to lead, he experienced onset of
      inflammatory symmetric polyarthritis with joint deformities. Hyperuricemia,
      moderately severe renal failure, and tubular acidosis were found, indicating
      gouty polyarthritis. Blood lead levels were high, establishing that the cause was
      lead poisoning. EDTA chelation therapy was effective. Lead poisoning is
      frequently under-recognized because the clinical manifestations are often minimal
      and the diagnosis difficult to establish. We suggest that lead bound to bone may
      result in continued exposure to lead after cessation of industrial or
      environmental exposure. Chelating agents are valuable for the diagnosis and can
      ensure a full recovery.

PMID- 12184439
TI  - Yellow nail syndrome associated with thiol compound therapy for rheumatoid
      arthritis. Two case reports.
AB  - Yellow nail syndrome is characterized by ungual dystrophy, lower limb lymphedema,
      and pleural effusions or bronchiectasis. Rheumatoid arthritis is the autoimmune
      disorder most often associated with yellow nail syndrome. We report two new cases
      of yellow nail syndrome in patents receiving thiol compound therapy for
      rheumatoid arthritis. Eight similar cases have been reported since 1979,
      suggesting a possible causative effect of this class of drugs.

PMID- 12184441
TI  - Muscular metastatic infiltration from pulmonary epidermoid carcinoma.
AB  - The localisation of metastasis in muscle is rare and is discovered mainly during
      autopsy. Skeletal muscle metastasis may occur in the case of leukaemia, lymphoma,
      melanoma, thyroid, gastrointestinal tract and breast carcinoma. However the most
      frequent aetiology is lung cancer. We describe the case of a 67-year-old woman,
      suffering from epidermoid lung carcinoma localised in both upper right lobes,
      treated surgically with success. Two months after surgery, she complained of pain
      and a sensation of swelling in the adductor muscles of the left hip with
      important restriction of mobility. A MRI scan of the hip showed an ovoid mass
      between the obturator extemus and the adductors muscles on the left side. Biopsy
      of the infiltrated muscles showed proliferation of carcinomatous tissue.

PMID- 12184442
TI  - Vascular involvement in Behcet's disease. Two case reports.
AB  - Arterial involvement is rare in Behcet's disease but can be at the forefront of
      the clinical picture and cause life-threatening complications. CASE REPORTS: A 36
      year-old man had Behcet's disease with an aortographically documented aneurysm of
      the abdominal aorta as the inaugural manifestation. He had oral and genital
      ulcers. Funduscopy showed periphlebitis. In a 38-year-old man with an 8-year
      history of Behcet's disease, pulmonary and coronary artery aneurysms developed,
      as well as intracardiac and venous thromboses. DISCUSSION: Arterial involvement
      occurs in 3-5% of patients with Behcet's disease and usually manifests as
      multiple spindle-shaped aneurysms. Intracardiac thrombosis and cardiac aneurysm
      are exceedingly rare. Our patient had an extremely unusual presentation given the
      low rate of occurrence of arterial lesions in Behcet's disease. CONCLUSION:
      Arterial involvement in Behcet's disease raises treatment challenges because the
      lesions tend to recur and can cause life-threatening complications.

PMID- 12184443
TI  - Diagnostic methods for detection of respiratory RNA viruses.
AB  - This article is a comprehensive description of diagnostic methods for detection
      of RNA respiratory viruses - respiratory syncytial virus RSV, influenza A and B
      viruses, parainfluenza 1, 2 and 3 viruses, coronaviruses and rhinoviruses--from
      cell culture to molecular biology methods. Both patients and medical personnel
      appear to be at risk of viral infection, specially during the winter season.
      Moreover, many health care units lack viral diagnostic facilities; therefore, it
      is essential for medical personnel to have an understanding of the etiology,
      mechanisms of transmission and of all disposable today diagnostic methods of RNA
      respiratory viruses. Patients at greatest risk of acquiring nosocomial viral
      respiratory disease are children, patients with immunodeficiency and patients
      treated in intensive care.

PMID- 12184444
TI  - Autoaggregation, hydrophobic, and hydrophylic properties of Moraxella catarrhalis
      strains.
AB  - The hydrophobicity of the bacterial cell surface was evaluated via the salt
      aggregation test (SAT) in 58 strains (19 from the lower and 39 from the upper
      respiratory tracts) of Moraxella catarrhalis in hospitalized patients aged 25 to
      65. Based on the SAT results, the strains were divided into three groups:
      autoaggregating (highly hydrophobic), hydrophobic, and hydrophilic. At a
      temperature of 37 degrees C, the autoaggregating, hydrophobic or hydrophilic
      properties did not depend on the choice of a medium, whereas at 22 degrees C the
      investigated properties did (p<0.0001). Taking into account the origin of the
      strains (lower vs. upper respiratory tract), it was found that: in the strains
      cultivated in liquid medium, both highly hydrophobic, hydrophobic and hydrophilic
      surfaces were present with a comparative frequency, independent of the strain
      isolation site and cultivation conditions; strains with highly hydrophobic and
      hydrophobic surfaces, but only those cultivated on solid media at 22 degrees C,
      were much more often isolated from sputum rather than from nose and throat swabs,
      whereas a statistically significant incidence of hydrophilic strains was found in
      samples from the upper rather than lower respiratory tract.

PMID- 12184445
TI  - A comparison of four susceptibility tests on Yersinia enterocolitica strains
      isolated from human and animal material.
AB  - The results of antibiotic sensitivity tests are presented for 20 strains of
      Yersinia enterocolitica from human and animal material as well as for one
      commercial standard strain. Results obtained with four different methods of
      assays were compared. One of the methods used was flow cytometric Minimum
      Inhibitory Concentration (MIC) assay (FC-MIC). Results of all four tests were
      comparable and were in range for Gentamycin sensitive strains. Problems of
      resistant bacterial strains in the clinical surrounding are discussed.

PMID- 12184446
TI  - Phenol removal in packed bed reactor under denitrifying conditions.
AB  - Detailed studies on the efficiency of phenol degradation by a biofilm in an
      anaerobic packed bed reactor were carried out. The efficiency of phenol
      degradation depended on both the concentration of phenol in the medium and the
      phenol load in anaerobic packed bed reactor. Increasing phenol concentrations
      from 200 to 1,250 mg l(-1) and retention time (Tr)= 12 h were paralleled by
      increasing efficiency of the process, which reached a maximum value of 1,390 mg
      l(-1) day(-1) at 700 mg phenol l(-1). The highest concentration of phenol used
      inhibited growth by approximately 95%. When the phenol load in medium containing
      200, 300, 400 and 500 mg l(-1) was increased through a shortening of the
      retention time (Tr from 24 to 2 h) a maximum efficiency of phenol degradation of
      2,200 mg l(-1) day(-1) was obtained at Tr=4 h and phenol concentrations in the
      medium of 200 mg l(-1). Phenol in concentrations from 300 to 500 mg l(-1) was
      fully degraded at Tr>9 h and phenol load reaching 530-1330 mg l(-1) day(-1) for
      the individual concentrations. The post-denitrification effluent leaving packed
      bed reactor in spite of the absence or even trace amounts of phenol in it
      requires further purification.

PMID- 12184447
TI  - Effect of nitrates on biotransformation of phosphogypsum and phenol uptake in
      cultures of autochthonous sludge microflora from petroleum refining wastewaters.
AB  - The effect of nitrates on the biotransformation of phosphogypsum at 30 degrees C
      in stationary cultures of anaerobic, heterogeneous microflora growing in medium
      with phenol (250-1,000 mg/L) as sole carbon source was studied. The
      microorganisms used in this study were isolated from sludge in biological
      petroleum-refining wastewater treatment plant. Phosphogypsum (a waste product in
      the chemical industry that contains approximately 95% CaSO4) was added in amount
      of 5 g/L, the source of nitrates was KNO3 in concentration equivalent to that of
      phenol (250-1,000 mg N-NO3/L). The presence of nitrates in heterogeneous cultures
      has an inhibitory effect on the process of phosphogypsum biotransformation and
      stimulates the uptake of phenol. We have found that in cultures in medium
      containing phenol, phosphogypsum and nitrates at least three physiological groups
      of microorganisms were present. These were phenol-biodegrading microorganisms not
      requiring an external electron acceptor, sulfate-reducing bacteria biodegrading
      phenol or intermediate products of its breakdown and denitrifying bacteria not
      utilising phenol as a carbon source. On solid medium these bacteria together
      formed heterogeneous single colonies. In spite of repeated attempts we were
      unable to isolate pure strains and the only result of these measures was loss of
      denitrification ability in medium with phenol.

PMID- 12184448
TI  - Penicillin-binding proteins of listeria monocytogenes--a re-evaluation.
AB  - Intact Listeria monocytogenes cells or membranes isolated from them were treated
      with [3H]penicillin to allow identification of the penicillin binding proteins
      (PBPs) located in the cytoplasmic membrane. In the former case the PBPs were
      released from the cells following disruption of the cell wall murein with
      Listeria monocytogenes bacteriophage lysin. The procedure described by Dougherty
      et al. (1996) for Escherichia coli, with some modifications, was used to evaluate
      the M(r)s of the individual PBPs and allowed direct quantitation of their copy
      number.

PMID- 12184449
TI  - Biotransformation of d-limonene to carvone by means of glucose oxidase and
      peroxidase.
AB  - A novel method for enzymatic biotransformation of limonene to carvone has been
      developed. It involves addition glucose oxidase and peroxidase to the
      biotransformation medium. Some factors affecting biotransformation yield were
      investigated. Maximal yield of carvone occurred in the medium containing 1.5%
      substrate, at 50 degrees C and pH 7.0.

PMID- 12184450
TI  - Microbiological studies of feed and faeces of fatteners fed mixtures containing
      naked oat and permutite.
AB  - Quantitative and qualitative microbiological studies of feed mixtures and faeces
      of fatteners with body weight approximately 70 kg receiving complete mixtures:
      group I (control)--55% barley, II--55% naked oat, III--55% naked oat + 3%
      permutite were conducted. All mixtures were supplemented with the same protein
      concentrate for fatteners. It was found that feeding the fatteners with mixtures
      containing naked oat had a favourable effect on the composition of the faecal
      microflora, with increased participation of Lactobacillus spp. bacteria. The
      addition of permutite did not visibly affect the composition of the microflora
      and the observed differences between the groups can be attributed to the species
      of cereal in the feed mixture, with naked oat being far more favourable than
      barley. The addition of permutite seems to have a beneficial effect on the
      condition of the faecal matter of these animals, which contained a larger number
      of Saccharomyces spp. cells.

PMID- 12184451
TI  - Effect of addition of "Greenline" preparations to feed mixtures for broilers on
      the composition of their intestinal microflora.
AB  - The current study deals with the possibility of replacing the antibiotic growth
      stimulator avilamycin, a mixture of oligosaccharides of the orthosomycin group,
      with the herbal preparations Greenline 1 and 2. The microbiological part of the
      study embraced examination of the intestinal microflora of broilers. The birds in
      the study belonged to four experimental groups, distinguished on the basis of
      feed supplements used. For the microbiological determination five birds from each
      group were selected at random and the contents of their small intestine was
      examined for given groups of microorganisms. The remaining birds in each group
      were examined and evaluated on the basis of zootechnical indices. Our results
      suggest that Greenline 1 efficiently eliminates certain pathogenic bacteria,
      above all lactose-positive bacteria belonging to the family Enterobacteriaceae
      and Staphylococci. It seems that the presence of Greenline 1 in the feed mix used
      enhances the colonisation of the mucous membrane of the studied chicken with
      Lactobacillus lactic acid bacteria. This is indicated by the considerably higher
      number of these bacteria in the small intestine of the birds receiving the
      supplement Greenline 1.

PMID- 12184452
TI  - Evaluation of antiviral activity of different origin compounds by flow cytometry.
AB  - Against many viral diseases caused for example by HSV, EBV, CMV, HIV, RSV, HCV
      for which vaccines are not available, chemiotherapeutics seem to have the
      principal significance. High progress in development of new antiviral compounds
      is observed. In addition to synthetic compounds a large number of naturally
      occurring substances have been shown to posses antiviral activity. One of such
      substance is tannic acid. In this study comparison of antiviral activity of
      tannic acid, acyclovir (ACV) and ganciclovir (GCV) against cytomegalovirus (CMV)
      is presented. The MRC5 cells infected with CMV and treated with different
      compounds were analyzed by flow cytometry and cythopatic effect inhibition test
      for inhibition of virus replication and by MTT assay for cytotoxity. It has been
      shown that tannic acid has antiviral activity against cytomegalovirus and that
      expression of virus antigens measured as median fluorescence intensity (MFI) by
      flow cytometry can be used for evaluation of virus replication.

PMID- 12184453
TI  - Health systems performance assessment.

PMID- 12184454
TI  - What does the World Health Report 2000 bring to Lebanon?
AB  - The World Health Report 2000 has been the subject of extensive debate. The
      authors highlight in the following, what they consider as major limitations that
      are either inherent to methods followed and the validity of data used, or related
      to the particular situation of Lebanon. This article tackles the first two of the
      set goals i.e. level of health and responsiveness as well as the overall system
      performance. The Report clearly states that extensive use has been made of
      estimates of indicators, and that there were often conflicting sources of
      information on these indicators. In the case of Lebanon, data was not available
      for most of the values used. In fact, the last national population census was
      conducted in 1932, and vital registration is incomplete. Therefore, one would
      question the value of the estimates, based on which the calculations were made
      for Lebanon, such as Life tables, and Causes of Deaths. Finally, the authors
      conclude that despite the critics, embarking in this exercise is useful for
      Lebanon, particularly at this stage, for monitoring the reform process in the
      health sector.

PMID- 12184455
TI  - What is fair in financing fairness?
AB  - The World Health Report 2000 considers "fair financing" as one of the three goals
      for assessing the Health Systems Performance. Fair financing cannot be
      dissociated from equity that implies traditionally getting the services one's
      needs in return for contributing within one's ability to pay. However, the
      calculation in the Report considers "fairness of financial contribution" which
      disregards accessibility to health services. In addition to their disagreement on
      the concept of fairness, the authors question the validity of the statistical
      method used. They notice that despite the absence of financial barriers to access
      health services, the scoring of Lebanon came unsatisfactory. They claim that the
      health system in Lebanon is rather contributing in redressing the inequity of the
      fiscal system.

PMID- 12184456
TI  - The epitaph of the advanced breast biopsy instrumentation (ABBI).

PMID- 12184457
TI  - Determinants of elevated blood lead levels among working men in Greater Beirut.
AB  - This cross-sectional study reports the blood lead levels (BLL) among different
      working groups in Beirut and identifies the risk factors associated with elevated
      BLLs. A total of 579 men of 18 years of age or older (response rate 96%) working
      in Greater Beirut were interviewed. Of those, 315 (54.4%) provided a blood sample
      of which 291 were analyzed for lead. The mean BLL of the 134 men working in white
      collar jobs (offices, retail shops) was 12.7 microg/dl (SD 3.7); statistically
      significantly lower than the mean BLL (18.4 microg/dl; SD 9.8) of the 157 men
      working in blue-collar occupations (such as gas station attendants, painters,
      mechanics). A blood lead level of 15 microg/dl or more was associated with blue
      collar jobs, number of cigarettes smoked, commuting > or = 3 km to work, years in
      current occupation, and younger age. A BLL of at least 20 microg/dl was
      associated with eating lunch at work, in addition to blue-collar jobs, smoking,
      commuting, years of work, and younger age. The study findings suggest that
      environmental exposure (those not otherwise exposed to occupational lead) is
      mainly determined by smoking and exposure to leaded gasoline (commuting).
      Occupational exposure to lead is prevalent among a wide spectrum of Lebanese
      workers. Physicians are called upon to inquire more about the potential for lead
      exposure, especially among blue-collar workers. A policy action to improve
      working conditions and to phase out the use of leaded gasoline is recommended.

PMID- 12184458
TI  - Lebanese population: prevalence of the erythrocyte phenotypes.
AB  - STUDY OBJECTIVES: This survey was designed to be a descriptive study of the
      erythrocyte phenotype prevalence in Lebanon. The general aim was to provide
      transfusion centers and blood banks with the occurrence of the nation's
      erythrocyte phenotypes in the population they are serving. The results were
      descriptively compared to Caucasians. SUBJECTS AND METHODS: 632 blood samples
      were collected from the Lebanese population in the 5 muhafazats (regions). Of
      which, 350 samples were extensively phenotyped for the blood group systems ABO,
      Kell, Kidd, Duffy, MNS, Lewis, Lutheran and P; and 282 samples were selectively
      phenotyped for Fy(a), Fy(b) and Kp(a). Additionally, 3064 random blood donors
      were studied for the ABO and D blood groups. MAIN RESULTS: With respect to the
      blood group phenotypes, the Lebanese are similar to the Caucasian population with
      the exception of rr, Le(b), Le (a-b-), Fy (a-b-), M+N+S-s+ and M-N-S-s+.
      CONCLUSION: It is of scientific cognizance and interest that the Lebanese
      erythrocyte phenotypes closely resemble that of the Caucasians: nevertheless,
      certain novel differences are present, and possibly, there exists a phenotype
      that attributes to admixture of the African gene in a Middle Eastern population.

PMID- 12184459
TI  - Cutaneous leishmaniasis: what about a new, inexpensive, effective, topical herbal
      remedy?
AB  - Cutaneous leishmaniasis (CL) remains an important disease and public health
      problem in many parts around the world especially in the Middle East. In the
      absence of adequate treatment, the lesion could become chronic and disfiguring.
      We report on three cases with chronic CL lesions that were successfully treated
      with topical application of a new herbal mixture named "Z-HE". It is clearly
      demonstrated that this inexpensive, simple, effective and non toxic topical drug
      has a promising curative role in the treatment of CL.

PMID- 12184460
TI  - Echinococcal cysts of the liver: epidemiology, imaging classification, diagnosis
      and management.

PMID- 12184461
TI  - Management of hirsutism in women of Mediterranean origin.

PMID- 12184462
TI  - West Nile virus: reasons for concern in Lebanon.

PMID- 12184463
TI  - Primary mediastinal liposarcoma: a case report and review of the literature.
AB  - A case of mediastinal liposarcoma (LPS) in a 49-year-old female is described.
      Primary LPS of the mediastinum are very rare tumors. They occur mainly in adults
      but may be encountered in children. They are characterized by their large size
      and their variable histologic subtypes, which correlate with the clinical
      behavior and the prognosis. The radiologic features are nonspecific but are
      suggestive of the diagnosis. A tissue biopsy is needed for the final diagnosis.
      The treatment of choice is surgical with wide margin resection. Chemotherapy and
      radiotherapy are ineffective modalities, used in unresectable or incompletely
      resected tumors. The prognosis depends on the histologic subtypes and
      completeness of surgical excision.

PMID- 12184464
TI  - A case of merosin-negative congenital muscular dystrophy with extensive white
      matter abnormalities and electroencephalographic changes in a Syrian boy.
AB  - Congenital muscular dystrophies are a group of heterogeneous disorders inherited
      as an autosomal recessive disease. In the Caucasians they are most frequently
      encountered as the so-called "pure" or occidental form. Recently it has been
      found that the severity of concomitant white matter changes depends on the
      presence or absence of merosin, the laminin isoform, in the skeletal muscle. The
      authors present a 2-year-old Syrian boy with congenital muscular dystrophy which
      proved to be merosin (laminin alpha2) deficient and believe that this is the
      first case described from Syria. The clinical picture, biochemical findings,
      neurophysiological investigations, biopsy findings and extensive abnormalities of
      white matter on magnetic resonance imaging (MRI) found in this case are
      presented. Peculiar electroencephalographic (EEG) pattern with fast rhythms in
      occipito-temporal regions is emphasized.

PMID- 12184465
TI  - Relationships between the United States and Lebanon.

PMID- 12184466
TI  - White coat hypertension'--should it be treated or not?

PMID- 12184467
TI  - Hyperuricemia and gout: a reign of complacency.

PMID- 12184468
TI  - Asymptomatic hyperuricemia: to treat or not to treat.
AB  - Treatment of asymptomatic hyperuricemia is not necessary in most patients, unless
      perhaps they have very high levels of uric acid or are otherwise at risk of
      complications, such as those with a personal or strong family history of gout,
      urolithiasis, or uric acid nephropathy.

PMID- 12184469
TI  - Progress in preventing chemotherapy-induced nausea and vomiting.
AB  - Our understanding of the pathophysiology of emesis has improved over the past 2
      decades, and we now have drugs that can prevent acute emesis in most patients.
      Prevention and treatment of the delayed and anticipatory forms of chemotherapy
      induced emesis remain a challenge.

PMID- 12184470
TI  - Inflammatory bowel disease: sorting out the treatment options.
AB  - An increasing array of treatments such as immunosuppressive drugs and tumor
      necrosis factor inhibitors can offer patients with ulcerative colitis and Crohn
      disease improved relief from symptoms with fewer adverse effects. Several
      additional drugs have shown promise, including nicotine, antimicrobials, and
      heparin.

PMID- 12184471
TI  - A 62-year-old man with hypotension and an abnormal chest radiograph.

PMID- 12184472
TI  - Two advances in the management of Parkinson disease.
AB  - Levodopa should generally be avoided early in the course of Parkinson disease;
      dopamine agonists, particularly second-generation agents such as ropinirole
      (Requip) and pramipexole (Mirapex), carry a smaller long-term risk of dyskinesia
      and should be used instead. Deep brain stimulation is remarkably effective in
      refractory cases and may well usher in a new era in the treatment of chronic
      neurologic disease.

PMID- 12184474
TI  - Patient information. Endometriosis: what it is and how it is treated.

PMID- 12184475
TI  - The spatial integration of adolescent identity: its relation to age, education,
      and subjective well-being.
AB  - A sense of being the same person through time and social contexts is a central
      characteristic of identity formation. The spatial integration of identity was
      investigated in three groups of high school students differing in age and/or
      educational level. The 294 adolescents chose and ranked personally revealing
      identity contexts, described their general and context-specific identities, and
      indicated their subjective sense of well-being. With increasing age and
      educational level adolescents chose an increasing number of identity contexts.
      Context-specific identities were found on average to be closely interwoven. There
      was a positive linear relationship between spatial integration and subjective
      well-being. The conclusion is that age and education promote the extension of
      adolescents' identity horizons, provided that their spatial integration is solid
      enough to absorb the downward effect of a new identity context. A comparison
      between spatial integration and two measures of exploration and commitment showed
      that spatial integration is a relatively powerful measure of adolescent identity.

PMID- 12184473
TI  - Endometriosis: still tough to diagnose and treat.
AB  - Endometriosis is a chronic disease that may have life-altering implications such
      as chronic pelvic pain and infertility. The following review will familiarize the
      practicing physician with available therapies to maintain and enhance
      reproductive potential and control pelvic pain in women with endometriosis.

PMID- 12184476
TI  - Right-left discrimination: effects of handedness and educational background.
AB  - The present study investigated right left discrimination, with a paper-and-pen
      test with cartoon figures. The test consisted of line drawings of a person with
      no, one, or both arms crossing the vertical axis of the body in the figure. The
      subjects' task was to mark with a pencil, as fast as possible, which was the
      right or left hand in the figure. The line drawings were viewed from the back,
      from the front, or randomly alternating between the back and front views. Two
      studies were conducted. The first consisted of 393 adults: 153 males and 240
      females; 338 right-handers and 55 left-handers. The results showed that the males
      performed better than the females. The left-handers and the right-handers
      performed equally well. However, the left-handed males performed better than the
      right-handed males. There was no difference in performance between the right
      handed and the left-handed females. The second study consisted of 175 right
      handed college students: 63 psychology students. 54 medical students, and 58 law
      students. The main finding was that the medical students performed better than
      the psychology students for all figure orientation subtests and for all arm
      positions. In comparison with the law students, the medical students performed at
      the same level on the back view subtest, but they performed better on the front
      view subtest and on two out of three arm positions on the alternating view
      subtest.

PMID- 12184477
TI  - Determinants of picture naming times in Icelandic.
AB  - Numerous studies have found that word frequency has a significant effect on the
      time it takes to name an object or read a word. Recently, claims have been made
      that this frequency effect is perhaps more correctly interpreted as an age of
      acquisition effect. This paper reports an experiment in which naming times in
      Icelandic for 175 stimuli from the Snodgrass and Vanderwart picture set were
      determined. A multiple regression analysis of naming times against a number of
      independent factors showed that objective age of acquisition was the strongest
      predictor of naming time, with familiarity and name agreement also showing a
      significant effect. The effect of word frequency was, however, not significant.
      Possible reasons for this are discussed.

PMID- 12184478
TI  - Risk-taking attitudes among young drivers: the psychometric qualities and
      dimensionality of an instrument to measure young drivers' risk-taking attitudes.
AB  - Adolescents are proportionately more frequently involved in traffic accidents
      than are other age groups. A strategy for promoting road safety is to change the
      attitudes likely to influence driving behavior. However, the lack of valid and
      reliable instruments to measure risk-taking attitudes makes it difficult to
      evaluate the effects of measures aimed at changing attitudes among young drivers
      and their passengers. The present study tested the psychometric qualities of a
      scale intended to measure adolescents' risk-taking attitudes to driving. The
      results are based on a self-completion questionnaire survey carried out among
      3,942 adolescents and young adults, aged 16-23 years, in Norway in 1998/1999.
      Using both exploratory and confirmatory factor analyses, 11 dimensions of risk
      taking attitudes were identified. Parametric as well as nonparametric methods
      were applied to test the homogeneity of items within each attitude dimension. The
      reliability and validity of the dimensions were satisfactory. The attitude
      dimensions were significantly correlated with self-reported driving behavior, as
      well as accident frequency. The application of the new measurement instrument in
      studies aimed at evaluating safety campaigns is discussed.

PMID- 12184479
TI  - Cognitive deficits in major depression.
AB  - Major depression is a mood disorder that is often accompanied by the impairment
      of cognitive functions. Although suggestive, the large range of existing
      neuropsychological, neuropsychiatric, and, lately, neuroimaging investigations
      have not yet given a consistent picture of the psychological and biological
      disturbances involved in this psychiatric disorder. The present study of the
      cognitive functions in depression was part of an extensive investigation,
      including neuropsychological testing, psychiatric examination, and neuroimaging.
      A representative sample of 40 severely depressed hospitalized patients and a
      group of 49 closely matched control subjects were tested with an extensive
      neuropsychological test battery. Results, corrected for various confounding
      factors, confirmed the current notion that depressed patients suffer from wide
      spread cognitive impairments. The group analysis did not allow any hypothesis on
      a possible pattern to the dysfunctions, but heterogeneity in the test
      performances calls for further analysis of the data in patient subgroups in
      relation to neuroimaging results.

PMID- 12184480
TI  - Does mood influence the realism of confidence judgments?
AB  - Previous research has shown that mood affects cognition, but the extent to which
      mood affects meta-cognitive judgments is a relatively over-looked issue. In the
      current study we investigated how mood influences the degree of realism in
      participants' confidence judgments (based on an episodic memory task). Using
      music and film in combination, we successfully induced an elated mood in half of
      the participants, but failed to induce a sad mood in the other half. In line with
      previous research, the participants in both conditions were overconfident in
      their judgments. However, and contrary to our prediction, our data indicated that
      there was no difference in the realism of the confidence between the conditions.
      When relating this result to previous research, our conclusion is that there is
      no, or very little, influence of mood of moderate intensity on the realism of
      confidence judgments.

PMID- 12184481
TI  - Effects of displayed emotion on attitude and impression formation in visual
      speech-reading.
AB  - In two experiments on visual speech-reading, with a total of 132 normal-hearing
      participants, the effects of displayed emotion and task specificity on speech
      reading performance, on attitude toward the task and on person impression were
      explored, as well as associations between speech-reading performance, attitude,
      and person impression. The results show that displayed emotion increased speech
      reading performance and attitude ratings, and that the actor was perceived as
      more extraverted both when displaying emotions, and when his speech was high in
      specificity The main conclusion was that displayed emotion enhances speech
      reading performance by providing information that is useful to the speech-reader.

PMID- 12184482
TI  - Learning difficulties, social intelligence, and self-concept: connections to
      bully-victim problems.
AB  - Learning skills, social intelligence, and self-concept were related to each other
      and to bully-victim problems among fifth-grade children (79 boys and 62 girls,
      aged 11-12 years). In addition to exploring connections between single variables,
      a person-oriented approach was applied in order to analyze children's value
      patterns with respect to learning skills, self-concept, and social intelligence,
      and how these value patterns are related to bully-victim problems. Social
      intelligence was found to be positively correlated with learning skills, but
      negatively related to victimization. Bullying was positively correlated with self
      concept scores. However, this was true only of boys. According to cross
      tabulations, there were significantly more bullies among children with learning
      difficulties (LD) than would have been expected by chance. Victimization, on the
      other hand, was not related to LD. LD children's proposed victim status was in
      some degree supported by cluster analysis: a group of LD children emerged, who
      not only scored high on bullying, but also tended to be victimized by others. In
      addition, two groups of bullies appeared: one whose members could be interpreted
      as socially unskilled and another as socially skilled. This finding is in line
      with recent theoretical reasoning, which calls into question the idea of bullies
      as a unified group, lacking in social skills.

PMID- 12184483
TI  - Review. The genotype-phenotype link.
AB  - The basic knowledge which has opened for the new discipline of functional
      genomics stems from one hundred years of debates and experimentation among
      devoted geneticists, who tried to understand the processing of gene expression
      into phenotypic design without the molecular tools that are now available. Here I
      recapitulate some old and some newer results from this research, which illustrate
      the ways in which changes in genetic variation can be induced, how it can be kept
      latent or, when needed, be expressed in the phenotype.

PMID- 12184484
TI  - Genotoxicity of maleic hydrazide, acridine and DEHP in Allium cepa root cells
      performed by two different laboratories.
AB  - The purpose of this paper was to compare the results of the Allium cepa
      chromosome aberration assay between two laboratories under the same test protocol
      and at the same time, use chemicals and onions obtained in their own homeland.
      For this study three chemicals were selected: di(2-ethylhexyl)phthalate (DEHP),
      maleic hydrazide, and acridine. Both laboratories found genotoxicity with a
      positive dose-response relationship for maleic hydrazide and acridine. However,
      for DEHP the results were quite different--one of the laboratories found this
      compound not genotoxic but the other found a positive response. Although the
      comparative study was inconclusive for DEHP, it was successful for the maleic
      hydrazide, acridine and also for the positive control (methyl methanesulfonate).
      Further studies need to be performed in the case of DEPH.

PMID- 12184485
TI  - DNA characterization and karyotypic evolution in the bee genus Melipona
      (Hymenoptera, Meliponini).
AB  - We analyzed patterns of heterochromatic bands in the Neotropical stingless bee
      genus Melipona (Hymenoptera, Meliponini). Group I species (Melipona bicolor
      bicolor, Melipona quadrifasciata, Melipona asilvae, Melipona marginata, Melipona
      subnitida) were characterized by low heterochromatic content. Group II species
      (Melipona capixaba, Melipona compressipes, Melipona crinita, Melipona seminigra
      fuscopilosa e Melipona scutellaris) had high heterochromatic content. All species
      had 2n = 18 and n = 9. In species of Group I heterochromatin was pericentromeric
      and located on the short arm of acrocentric chromosomes, while in Group II
      species heterochromatin was distributed along most of the chromosome length. The
      most effective sequential staining was quinacrine mustard (QM)/distamycin
      (DA)/chromomycin A3(CMA3)/4-6-diamidino-2-phenylindole (DAPI). Heterochromatic
      and euchromatic bands varied extensively within Group I. In Group II species
      euchromatin was restricted to the chromosome tips and it was uniformly GC+.
      Patterns of restriction enzymes (EcoRI, DraI, HindIII) showed that
      heterochromatin was heterogeneous. In all species the first pair of homologues
      was of unequal size and showed heteromorphism of a GC+ pericentromeric
      heterochromatin. In M. asilvae (Group I) this pair bore NOR and in M.
      compressipes (Group II) it hybridized with a rDNA FISH probe. As for Group I
      species the second pair was AT+ in M. subnitida and neutral for AT and GC in the
      remaining species of this group. Outgroup comparison indicates that high levels
      of heterochromatin represent a derived condition within Melipona. The pattern of
      karyotypic evolution sets Melipona in an isolated position within the Meliponini.

PMID- 12184487
TI  - Molecular mapping and genetic analysis of a rice brown planthopper (Nilaparvata
      lugens Stal) resistance gene.
AB  - The brown planthopper (BPH), Nilaparvata lugens Stal, is a serious insect pest of
      rice (Oryza saliva L.). We have determined the chromosomal location of a BPH
      resistance gene in rice using SSR and RFLP techniques. A rice line 'B14', derived
      from the wild rice Oryza latifolia, showed high resistance to BPH. For tagging
      the resistance gene in 'B14X', an F2 population and a recombinant inbred (RI)
      population from a cross between Taichung Native 1 and 'B14' were developed and
      evaluated for BPH resistance. The results showed that a single dominant gene
      controlled the resistance of 'B14' to BPH. Bulked segregant SSR analysis was
      employed for identification of DNA markers linked to the resistance gene. From
      the survey of 302 SSR primer pairs, three SSR (RM335, RM261, RM185) markers
      linked to the resistance gene were identified. The closest SSR marker RM261 was
      linked to the resistance gene at a distance of 1.8 cM. Regions surrounding the
      resistance gene and the SSR markers were examined with additional RFLP markers on
      chromosome 4 to define the location of the resistance gene. Linkage of RFLP
      markers C820, R288, C946 with the resistance gene further confirmed its location
      on the short arm of chromosome 4. Closely linked DNA markers will facilitate
      selection for resistant lines in breeding programs and provide the basis for map
      based cloning of this resistance gene.

PMID- 12184486
TI  - Genetic diversity amongst landraces of rye (Secale cereale L.) from northern
      Europe.
AB  - Genetic variation and diversity were estimated for three improved varieties and
      18 landraces of Secale cereale, originating from the northern Europe. This
      material was compared with eight improved varieties and 16 landraces from Sweden,
      which were analysed before. The analysis used starch gel electrophoresis with the
      enzymes ACO, GPI, MDH, PGD and PGM and resulted in one fixed locus and seven
      polymorphic loci. Most of the genetic diversity was found within the accessions
      and it was very small between accessions. The results show that the landraces
      from Germany and Norway have a low genetic variation compared to the other
      landraces in this study. This can possibly be explained with a small original
      sample size of some accessions. However, in the dendrogram these accessions are
      well separated. The landraces from Sweden and Finland showed a high genetic
      variation, which is almost the same for all these accessions. In the dendrogram
      all of the Finnish landraces and 11 of the Swedish ones were grouped together
      with a very small diversity index; they can almost be considered as part of the
      same accession. This is probably due to the fact that a high number of Finnish
      immigrants arrived in Sweden during the 17th century bringing their own rye
      material. The early Finnish rye landraces may have the same original source. The
      data also show that landraces as well as improved varieties have a high
      heterozygosity but they are separated in the dendrogram into different clusters.
      The currently used varieties show a large genetic distance variation, different
      from that in the landraces.

PMID- 12184488
TI  - Genetic variation in Arabidopsis suecica and its parental species A. arenosa and
      A. thaliana.
AB  - Random amplified polymorphic DNA (RAPD) markers were used to estimate the level
      of genetic variation in Swedish accessions of the allopolyploid Arabidopsis
      suecica and its parental species A. thaliana and A. arenosa. The results showed
      clear differences among the three species with respect to the level of variation.
      A. arenosa was highly variable, A. thaliana showed a moderate level of variation
      whereas A. suecica was much less variable than the two other species. An extended
      analysis covering 19 Swedish populations of A. suecica corroborated the low level
      of variation in this species, yet 16 unique phenotypes were observed. No
      isolation by distance was observed. When the genetic variation was partitioned
      among and within populations of A. suecica, the results showed that the majority
      of the variation (81%) occurred among populations. This result is interpreted as
      a strong indication that A. suecica is autogamous in nature.

PMID- 12184489
TI  - Comparative cytogenetics and supernumerary chromosomes in the Brazilian lizard
      genus Enyalius (Squamata, Polychrotidae).
AB  - Cytogenetical analyses based on conventional and differential staining were
      performed for the first time on five species of the Brazilian lizard genus
      Enyalius: E. bibronii, E. bilineatus, E. iheringii, E. leechii, and E. perditus.
      The species share a similar 2n = 36 (12M + 24m) karyotype, comprised of 12
      metacentric or submetacentric macrochromosomes, except for an acrocentric pair 6
      that characterizes E. bibronii. The 24 microchromosomes were acrocentrics, but in
      E. perditus two meta/submetacentric microchromosome pairs were unambiguously
      identified. Karyotypes with 2n = 37 and 2n = 37/38 chromosomes were also observed
      in some specimens of E. bilineatus as a result of the presence of supernumerary
      chromosomes (Bs). Ag-NORs were always located at the distal region of the long
      arm of the submetacentric pair 2. The constitutive heterochromatin was mostly
      restricted to the pericentromeric regions of some macrochromosomes and
      microchromosomes. A XX:XY mechanism of sex determination with a dot-like Y
      microchromosome occurs in E. bilineatus, E. leechii, and E. perditus.

PMID- 12184490
TI  - Chromosome composition, stability and fertility of alloploids between Triticum
      turgidum var. carthlicum and Thinopyrum junceiforme.
AB  - Alloploids, most of them hexaploid, from crosses between tetraploid wheat,
      Triticum carthlicum, and the perennial tetraploid Thinopyrum junceiforme were
      analysed for chromosome composition, stability and fertility using genomic in
      situ hybridization and meiotic analysis. The alloploids differed in their total
      number of chromosomes, 38-47 + telocentrics in "hexaploids" and 54 and 56 in
      "octoploids", and also in their number of Thinopyrum chromosomes (8-15).
      Translocations, mostly Robertsonian ones, were frequently found and intergenomic
      pairing was found to occur during meiosis. The stability was low which is
      reflected in the variability in chromosome number and in the number of univalents
      per PMC (2.3-4.0). The seedset was lower than in wheat, but high enough to secure
      a safe propagation and preservation. The alloploids are discussed in relation to
      widening the genetic variation of breadwheat and wheat breeding.

PMID- 12184491
TI  - Characterization of genetic diversity in core collection accessions of wild
      barley, Hordeum vulgare ssp. spontaneum.
AB  - Genetic variability in the 143 core accessions of wild barley, Hordeum vulgare
      ssp. spontaneum, was assessed by allozyme analysis. A total of 34 alleles were
      detected at ten isozyme loci. All loci were polymorphic except Pgd-1, which was
      monomorphic. Est-2 and Est-4 were the most diverse loci, with genetic diversity
      values of 0.747 and 0.686, respectively. The comparison of the results with those
      of previous studies indicates that all alleles occurring in cultivated and wild
      barley are observed in this set of the wild Barley Core Collection. Only one
      allele (Pgd-1 Tj) was absent. It is noteworthy that one new allele at the Ndh-2
      locus and another new allele at Aco-2 locus were first detected in the present
      study. Nine of the 34 alleles were rare and detected only in one to four
      accessions. The genetic similarities among the 143 accessions ranged from 0.18 to
      1.00. Data analysis based on clustering and principal coordinate analysis showed
      that a high level of genetic variability exists in this set of core accessions,
      and indicated that some duplication probably exists in this set core based on the
      present study.

PMID- 12184492
TI  - Mitotic and meiotic chromosomes in Somatochlora metallica (Cordulidae, Odonata).
      The absence of localized centromeres and inverted meiosis.
AB  - Spermatogonial metaphase chromosomes were examined in two dragonfly species,
      Somatochlora metallica (Cordulidae) and Aeshna grandis (Aeshnidae), and the
      behaviour of male meiotic chromosomes was studied in S. metallica. Both in S.
      metallica and A. grandis the male mitotic metaphase chromosomes from cells
      treated with colchicine consisted of two equidistantly aligned chromatids,
      showing no primary constriction. In meiosis the chromosomes of S. metallica males
      showed telokinetic activity during the first meiotic division, and kinetic
      activity was restricted in the middle parts of chromosomes during the second
      division. The kinetic behaviour of the chromosomes both in mitosis and meiosis
      showed that they were holocentric. One chiasma arises interstitially in each
      bivalent in S. metallica male meiosis. The chiasmata retain their interstitial
      position at metaphase I and do not terminalize. At metaphase I bivalents co
      orient with homologous telomere regions towards the opposite poles. Thus genuine
      dyads segregate at the first anaphase. Meiosis in these male dragonflies is thus
      pre-reductional or conventional, not post-reductional or inverted, as has been
      previously proposed.

PMID- 12184493
TI  - Structure of variation in enzyme activity in natural Drosophila melanogaster
      populations.
AB  - Enzyme activity variation was assessed in several isofemale lines originating
      from two Hungarian Drosophila melanogaster populations. Samples from each
      population were taken from from two villages; 8-9 isofemale lines were
      established from each village. The activities of ADH, alphaGPDH, IDH and 6PGDH
      were determined in the adults (in the F1 generation) and in the larvae (in the F3
      generation) as well. Enzyme activities were measured on starch gel after
      electrophoresis. The activity of the enzyme was detected in a single individual
      and it was also possible to determine its genotype. The results showed that most
      of the variation occurred within sites for all four enzymes. This within site
      variation was more or less equally partitioned into within and between isofemale
      line (family) components. A smaller portion of variation was attributable to the
      differences between the populations. Nevertheless, adult alphaGPDH, and larval
      IDH and 6PGDH activities exhibited significant differences between the two
      populations. Variation in larval activities of all enzymes was higher than that
      of the adults, but 6PGDH had considerably higher variation in the adults. The
      greater variation in larval activities probably reflected the greater
      environmental variation in the microhabitat of the larvae compared to that of the
      adults. Larval activities of the investigated enzymes showed much stronger
      correlation than adult activities. The correlation pattern in the adults differed
      greatly between the two populations.

PMID- 12184494
TI  - Brief report. The karyotype of the caudate amphibian Andrias davidianus.

PMID- 12184495
TI  - Conjunctival microflora in clinically normal Asian elephants in Thailand.

PMID- 12184496
TI  - Efficacy of sarafloxacin in broilers after experimental infection with
      Escherichia coli.
AB  - Infections of chickens with Escherichia coli serotype O78 can be treated with the
      antibiotic sarafloxacin. Three experiments were conducted on the administration
      of this drug to chickens that had been experimentally infected with E. coli. The
      birds were monitored for 10 days after infection for their average daily gain
      (ADG) and feed conversion ratio (FCR), and the post-mortem pathology was
      assessed. In the first experiment, sarafloxacin (20 mg/L, equivalent to 5 mg/kg
      live weight per day), given in the drinking water for 3 days after infection, led
      to a reduction in the mortality from 75% to 27%, but the ADG of the treated birds
      was still less than that of the uninfected controls. In the second experiment,
      when the sarafloxacin was administered at the same dose in the water but over
      only 2 h, there was also a considerable reduction in mortality, and the ADG and
      the FCR also improved significantly. In the third experiment, the dose dependence
      of the drug was tested. The birds were given 5 and 10 mg/kg per day sarafloxacin
      in each group, starting within 2 h after infection. This rapid administration of
      the drug completely prevented mortality, while the ADG and FCR were similar to
      those of the uninfected controls.

PMID- 12184497
TI  - Studies on the putative interactions between the organophosphorus insecticide
      Phosmet and recombinant mouse PrP and its implication in the BSE epidemic.
AB  - It has been suggested that exposure of cattle to the ectoparasiticide Phosmet in
      the 1980s caused a conformational change in the cellular prion protein (PrP(C))
      to form the BSE prion (PrP(SC)), which initiated the epidemic of bovine
      spongiform encephalopathy (BSE). Recombinant mouse cellular prion
      (r[mouse]PrP(C)) was exposed to the organophosphorus pesticide Phosmet in vitro
      and the conformation of the prion before and after exposure was monitored using
      circular dichroism (CD) spectroscopy, utilizing synchrotron radiation at the
      Council for the Central Laboratory of the Research Councils (CLRC) facilities at
      Daresbury, UK. Metabolites of Phosmet, generated in situ by rat microsomes, were
      investigated in the same way, to determine whether they might initiate the
      conformational change due to their high chemical reactivity. Our studies showed
      that exposure of r[mouse]PrP(C) to Phosmet or microsomes-generated metabolites of
      Phosmet did not result in the conformational change in the protein from alpha
      helix to beta-pleated sheet that is characteristic of the PrP(C) to PrP(SC)
      conversion and, therefore, Phosmet is very unlikely to have initiated the BSE
      epidemic by a simple direct mechanism of conformational change in the prion
      protein.

PMID- 12184498
TI  - Immunophenotyping of leukocyte subsets in peripheral blood and palatine tonsils
      of prefattening pigs.
AB  - The quantitative and distribution patterns of porcine peripheral blood and
      tonsillar lymphoid/myeloid cell subsets were assessed in order to establish the
      immune status of farm pigs prior to their transfer to fattening units. Peripheral
      blood and tonsillar samples were taken from clinically healthy, nonvaccinated, 12
      week-old pigs, either ex vivo or following euthanasia. Single-colour flow
      cytometry, using monoclonal antibodies (mAbs) reactive with the swine leukocyte
      cluster of differentiation (CD) antigens, gave the proportions of lymphoid (9.7%
      CD4+, 8.0% CD8+, 36.9% CD5a+, 20.3% CD16+, 6.9% CD21+, 86.3% CD45+, 41.8%
      CD45RA+, 48.3% CD45RC+), null cells (6.9%) and myeloid cells (23.7% CD11b+ and
      5.4% SWC3a+) in peripheral blood. In situ identification and distribution of
      lymphoid cells in the tonsils (CD3a+, CD21+, CD45RA+, CD45RC+) was performed with
      anti-CD mAbs using the avidin-biotin complex method. Most CD3a+ cells were in the
      parafollicular areas, with many cells in the follicles. CD21+ cells were
      scattered throughout the parafollicular area, with only a few cells inside
      lymphoid follicles. CD45RA+ cells were mostly concentrated in the follicles but
      many positive cells were present in the parafollicular area. Many CD45RC+ cells
      were visible in the parafollicular area, a few positive cells were in the crypt
      epithelium, and single cells were inside the follicles.

PMID- 12184499
TI  - Alpha-fetoprotein in canine multicentric lymphoma.
AB  - The concentrations of AFP were evaluated in the sera from groups of healthy dogs
      and of dogs with multicentric lymphoma, before and while receiving chemotherapy.
      The concentration of AFP was highest in the affected dogs, especially during the
      fifth stage of lymphoma. Chemotherapy caused a decrease in AFP serum
      concentration, during both the induction and the maintenance phases of treatment,
      when compared to the same animals before therapy. Determination of the
      concentration of AFP in the serum may be an additional indicator in the
      evaluation of the stage of lymphoma, and of value in assessing the extent of
      neoplastic infiltration of the liver.

PMID- 12184500
TI  - Schirmer tear test in clinically normal Asian elephants.

PMID- 12184501
TI  - Surgical extraction of transplanted adult Dirofilaria immitis in cats.
AB  - A jugular venotomy technique was developed to attempt extraction of Dirofilaria
      immitis in cats. Seven cats were first examined by cardiac ultrasound to
      establish the location of adult D. immitis that had been inserted by jugular
      venotomy. The efficiency of an extractor catheter in surgically removing filariae
      similarly inserted into 13 experimental cats was then assessed. A mean extraction
      success rate of 96% was achieved. This technique would seem to be worthy of
      clinical use provided the filariae are in the right atrial area.

PMID- 12184502
TI  - Possible anxiolytic effects of ivermectin in rats.
AB  - Ivermectin, a mixture of 22,23-dihydroavermectin B1a (> or = 80%) and B1b (< or
      =20%), is produced by Streptomyces avermectilis, an actinomycete. It is a
      macrocyclic lactone disaccharide, a member of the avermectin family, and is used
      as an antiparasitic drug. Previous studies performed in our laboratory showed
      that doramectin, another avermectin drug, interferes with GABAergic-related
      behaviours, leading to anxiety and seizures. The objective of the present study
      was to examine the effects of ivermectin (0.5 and 1.0 mg/kg) on the central
      nervous system of rats, using behavioural models related to GABAergic
      neurotransmission. A known anxiolytic drug, diazepam, was used as a positive
      control. Open field and elevated plus-maze behaviours, as well as conflict
      behaviour to a conditioned response, were assessed. The effects of ivermectin and
      diazepam in reversing the anxiety induced by picrotoxin was studied. The
      protective effects of ivermectin on pentylenetetrazole- and picrotoxin-induced
      seizures were also investigated. In the open field, 1.0 mg/kg ivermectin
      decreased locomotion frequency at 15 and 60 min of observation, rearing behaviour
      showed a biphasic effect at 15 and 30 min and duration of immobility was
      increased in all sessions after 1.0 mg/kg ivermectin. These data suggest
      anxiolytic or sedative effects. Ivermectin and diazepam both had a tendency to
      cause an increase both in the number of entries into the open arms and on the
      time spent in the open arms of an elevated plus-maze. Picrotoxin on its own
      reduced the number of entries as well as the time spent in the open arms. Both
      diazepam and ivermectin reversed these effects of picrotoxin. In conflict
      behaviour analysis, ivermectin and diazepam gave the classic effect of an
      anxiolytic drug, reversing the conditioned response to shock. Ivermectin
      protected rats from the convulsant effects of pentylenetetrazole but not from
      those of picrotoxin. Thus, ivermectin had the pharmacological profile of an
      anxiolytic drug with GABAergic properties. The lack of effect on seizures induced
      by picrotoxin suggests that the action of ivermectin is different from that of
      the benzodiazepine drugs.

PMID- 12184503
TI  - Chiral inversion of (R)-(-)-fenoprofen in guinea-pigs pretreated with clofibrate.
AB  - The influence of clofibrate on the stereoconversion of fenoprofen (FPF) was
      studied in guinea pigs. This hypolipidaemic agent has been related to some
      biochemical changes in the liver leading to an increase in the chiral inversion
      process. Two groups of animals (n = 6 per group) were pretreated with oral doses
      of clofibrate (280 mg/kg per day) for three days and were then given (R)- or (S)
      FPF (5 mg/kg, IV). The FPF enantiomers were extracted from the guinea-pigs'
      plasma using a solid phase procedure and analysed by HPLC with previous
      derivatization with L-leucinamide. Pretreatment with clofibrate increased the
      chiral inversion of (R)-FPF in favour of the pharmacologically active (S)-FPF
      enantiomer. Before this metabolic interaction can be applied to therapy with
      fenoprofen, the toxic effects of (S)-(+)-FPF on the gastrointestinal and renal
      tracts and the interference by (R)-(-)-FPF with the metabolism of lipids should
      be thoroughly evaluated.

PMID- 12184504
TI  - Review of 2,4-dichlorophenoxyacetic acid (2,4-D) epidemiology and toxicology.
AB  - The scientific evidence in humans and animals relevant to cancer risks,
      neurologic disease, reproductive risks, and immunotoxicity of 2,4-D was reviewed.
      Despite several thorough in vitro and in vivo animal studies, no experimental
      evidence exists supporting the theory that 2,4-D or any of its salts and esters
      damages DNA under physiologic conditions. Studies in rodents demonstrate a lack
      of oncogenic or carcinogenic effects following a lifetime dietary administration
      of 2,4-D. Epidemiologic studies provide scant evidence that exposure to 2,4-D is
      associated with soft tissue sarcoma, non-Hodgkin's lymphoma, Hodgkin's disease,
      or any other cancer. Overall, the available evidence from epidemiologic studies
      is not adequate to conclude that any form of cancer is causally associated with
      2,4-D exposure. There is no human evidence of adverse reproductive outcomes
      related to 2,4-D. The available data from animal studies of acute, subchronic,
      and chronic exposure to 2,4-D, its salts, and esters show an unequivocal lack of
      systemic toxicity at doses that do not exceed renal clearance mechanisms. There
      is no evidence that 2,4-D in any of its forms activates or transforms the immune
      system in animals at any dose. At high doses, 2,4-D damages the liver and kidney
      and irritates mucous membranes. Although myotonia and alterations in gait and
      behavioral indices are observed after overwhelming doses of 2,4-D, alterations in
      the neurologic system of experimental animals are not observed with the
      administration of doses in the microgram/kg/day range. It is unlikely that 2,4-D
      has any neurotoxic potential at doses below those required to induce systemic
      toxicity.

PMID- 12184505
TI  - Toxicity of fire smoke.
AB  - This review is an attempt to present and describe the major immediate toxic
      threats in fire situations. These are carbon monoxide, a multitude of irritating
      organic chemicals in the smoke, oxygen depletion, and heat. During the past 50
      years, synthetic polymers have been introduced in buildings in very large
      quantities. Many contain nitrogen or halogens, resulting in the release of
      hydrogen cyanide and inorganic acids in fire smoke as additional toxic threats.
      An analysis of toxicological findings in fire and nonfire deaths and the results
      of animal exposures to smoke from a variety of burning materials indicate that
      carbon monoxide is still likely to be the major toxicant in modern fires.
      However, the additional toxic threats mentioned above can sometimes be the
      principal cause of death or their addition can result in much lower than expected
      carboxyhemoglobin levels in fire victims. This analysis also revealed that
      hydrogen cyanide is likely to be present in appreciable amounts in the blood of
      fire victims in modern fires. The mechanisms of action of acute carbon monoxide
      and hydrogen cyanide poisonings are reviewed, with cases presented to illustrate
      how each chemical can be a major contributor or how they may interact. Also,
      lethal levels of carboxyhemoglobin and cyanide in blood are suggested from an
      analysis of the results of a large number of fire victims from different fire
      scenarios. The contribution of oxygen depletion and heat stress are more
      difficult to establish. From the analysis of several fire scenarios, they may
      play a major role in the room of origin at the beginning of a fire. The results
      in animal studies indicate that when major oxygen depletion (<10%) is added to
      lethal or sublethal levels of carbon monoxide or hydrogen cyanide its major role
      is to substantially reduce the time to death. In these experiments the
      carboxyhemoglobin level at death was slightly reduced from the expected level
      with exposure to carbon monoxide alone. However, blood cyanide was reduced by a
      factor of ten from the expected level with exposure to hydrogen cyanide alone.
      This is another factor (among many other presented) complicating the task of
      establishing the contribution of cyanide in the death of fire victims, from its
      analysis in their blood. Finally the role of ethanol intoxication, as it may
      influence carboxyhemoglobin levels at death, is reviewed. Its role is minor, if
      any, but the data available on ethanol in brain tissue and blood of fire victims
      confirmed that brain ethanol level is an excellent predictor of blood ethanol.

PMID- 12184506
TI  - Methods for assessing risks of dermal exposures in the workplace.
AB  - The skin as a route of entry for toxic chemicals has caused increasing concern
      over the last decade. The assessment of systemic hazards from dermal exposures
      has evolved over time, often limited by the amount of experimental data
      available. The result is that there are many methods being used to assess safety
      of chemicals in the workplace. The process of assessing hazards of skin contact
      includes estimating the amount of substance that may end up on the skin and
      estimating the amount that might reach internal organs. Most times, toxicology
      studies by the dermal route are not available and extrapolations from other
      exposure routes are necessary. The hazards of particular chemicals can be
      expressed as "skin notations", actual exposure levels, or safe exposure times.
      Characterizing the risk of a specific procedure in the workplace involves
      determining the ratio of exposure standards to an expected exposure. The purpose
      of this review is to address each of the steps in the process and describe the
      assumptions that are part of the process. Methods are compared by describing
      their strengths and weaknesses. Recommendations for research in this area are
      also included.

PMID- 12184507
TI  - A model of integrated care in assisted living for residents with dementia: mixed
      populations can promote harmony.

PMID- 12184508
TI  - Alternative therapies.

PMID- 12184509
TI  - Evidence and mechanisms of retrogenesis in Alzheimer's and other dementias:
      management and treatment import.
AB  - Retrogenesis is the process by which degenerative mechanisms reverse the order of
      acquisition in normal development. Alzheimer's disease (AD) and related
      conditions in the senium have long been noted to resemble "a return to childhood"
      Previously, we noted that the functional stages of AD precisely and remarkably
      recapitulated the acquisition of the same functional landmarks in normal human
      development. Subsequent work indicated that this developmental recapitulation
      also applied to the cognitive and related symptoms in AD. Remarkably, further
      investigations revealed that the same neurologic "infantile" reflexes, which mark
      the emergence from infancy in normal development, are equally robust indicators
      of corresponding stages in AD. Neuropathologic and biomolecular mechanisms for
      these retrogenic processes are now evident. For example, the pattern of myelin
      loss in AD appears to mirror the pattern of myelin acquisition in normal
      development. Also, recent findings indicate that mitogenic factors become
      reactivated in AD, and, consequently, the most actively "growing" brain regions
      are the most vulnerable. Because of this robust retrogenic process, the stages of
      AD can be translated into corresponding developmental ages (DAs). These DAs can
      account for the overall management and care needs of AD patients. A science of AD
      management can be formulated on the basis of the DA of the Alzheimer's patient,
      taking into consideration differences of AD from normal development as well as
      homologies.

PMID- 12184510
TI  - Discourse-derived perspectives: differentiating among spouses' experiences of
      caregiving.
AB  - A method of constant comparative analysis was used to code open-ended interviews
      with 132 spouse caregivers regarding their experiences in caregiving. Results of
      this analysis yielded 69 qualitative code categories. We used these categories to
      compare the caregivers on several groupings that the literature has identified as
      providing meaningful ways to differentiate among caregivers. We used the
      qualitative responses to compare the caregivers by caregiver gender care
      recipient dementia severity, and duration of caregiving. Results partly confirmed
      previous findings that wife caregivers are more distressed than husbands, but the
      results also indicated these caregivers were more similar than dissimilar The
      other analyses likewise indicated greater similarities than dissimilarities in
      the caregiving experience. We next continued the analysis and, using the coding
      categories as a springboard, identified four distinct patterns for construction
      of the meaning of the caregiving experience in the caregivers' discourse. These
      discourse-derived framing categories, applicable in about three-quarters of the
      caregivers, offered other ways to distinguish among caregivers. Further analysis
      of these robust groupings' showed important differences among the groups. These
      framing categories suggest ways to differentiate among caregivers, based on their
      perception of their role in the caregiving situation, ways that might point the
      way to intervention strategies for each of the groupings.

PMID- 12184511
TI  - Disrupted caring attachments: implications for long-term care.
AB  - Caring attachments or social supports are the positive psychological and physical
      contacts and relationships between people. These attachments have been associated
      with improved health, well-being, and longevity. It is also true that disrupted
      caring attachments are associated with impaired health and well-being. This paper
      reviews the general medical and elder medical findings of disrupted caring
      attachments and negative health outcomes. The implications of these findings for
      dementia sufferers, caregivers, and long-term care staff are examined.

PMID- 12184512
TI  - Leadership: key to creating a caring culture.
AB  - The subject of leadership is rarely addressed in the health care literature and
      the field is essentially silent to the need for leadership in long-term care. In
      this article, leadership is defined as the art of influencing and engaging
      colleagues to serve collaboratively toward a shared vision. The leadership model
      includes passion; commitment; vision; service; education; inclusion of staff
      patients, andfamilies; and self-knowledge.

PMID- 12184513
TI  - Decision-making for persons with cognitive impairment and their family
      caregivers.
AB  - Despite the large number of persons affected by cognitive impairment, very little
      is known about how they and their families make choices and decisions about
      everyday living and long-term care. Moreover few studies have examined the
      concept of consumer direction, particularly the ability ofcognitively impaired
      persons to delegate decision-making to other persons. This study explored
      decision-making through personal interviews with 51 respondent pairs, or dyads
      (i.e., the cognitively impaired person and the family caregiver). Results suggest
      that persons with mild to moderate cognitive impairment are able to answer
      questions about their preferences for daily care and to choose a person, usually
      a spouse or adult child, to make a variety of decisions on their behalf by
      recognizing both voices-those of the care receiver and the family caregiver--we
      can enhance future research and practice, foster the development of consumer
      direction in long-term care, and advance public policy to support caregiving
      families.

PMID- 12184514
TI  - Finding a practical method to increase engagement of residents on a dementia care
      unit.
AB  - Previous research has shown that it is possible to increase the engagement of
      residents with dementia in daily activities by making changes in institutional
      care practices. However, these changes often require expensive and cumbersome
      staff training programs that long-term care facilities may be unlikely to adopt
      and maintain. This study evaluates a simple, inexpensive recording and feedback
      procedure to increase resident engagement in a way that may be more amenable to
      adoption by long-term care facilities. Nursing assistants working in a locked
      dementia care unit were asked to complete a daily activity record on which they
      recorded the amount and quality of resident engagement. The facility's activity
      director was asked to read these activity records each day and give immediate,
      positive feedback to the nursing assistants. This procedure was evaluated by
      using a control series design. Results revealed baseline engagement observations
      with a mean of 11 percent, which increased to a mean of 44 percent during
      observations under treatment conditions. This study suggests that simple,
      inexpensive changes in institutional practices can make meaningful improvements
      in the level of engagement of residents with dementia.

PMID- 12184515
TI  - The underdetection of pain of dental etiology in persons with dementia.
AB  - BACKGROUND: The detection of dental pain in persons suffering from dementia has
      not yet been investigated. SUBJECTS AND METHODS: Twenty-one nursing home
      residents with a mean age of 88 participated in this study. Nine rotating
      volunteer dentists came to the nursing home to conduct dental evaluations. Two
      outside geriatricians performed a second assessment, and additional information
      concerning dental status was obtained from the minimum data set (MDS). RESULTS:
      Over 60 percent of assessed participants were considered to have a pain-causing
      condition. Less than half of these were rated by the geriatricians as having
      dental related pain. Only one participant was rated to have dental or mouth pain
      on the MDS. Only one of the 18 persons with either a full or partial evaluation
      had no dental problems. CONCLUSIONS: Dental problems are underdetected and
      undertreated in the nursing home. Better training for non-dentists in detection
      of such problems and better reimbursement for dental care are needed to improve
      care of residents.

PMID- 12184517
TI  - Disturbances in essential fatty acid metabolism in patients receiving long-term
      home parenteral nutrition.
AB  - Patients receiving home total parenteral nutrition (HTPN) are at risk for the
      development of essential fatty acid deficiency (EFAD). This study examined the
      essential fatty acid status of patients on long-term HTPN for gut failure. Serum
      phospholipid and triglyceride fatty acids were measured in 11 patients and 10
      healthy volunteers. Patients had similar levels of linoleic acid (18:2w6) in
      serum triglyceride fatty acids but significantly lower levels of 18:2w6 in serum
      phospholipids compared to controls. Although there was accumulation of Mead acid
      (20:3w9) in both fatty acid fractions, the ratio of 20:3w9 to arachidonic acid
      (20:4w6) remained less than 0.2, reflecting an adequate essential fatty acid
      status in these patients. There were, however, substantial increases in 20:4w6
      content in both triglyceride and phospholipid fractions in serum despite the
      lower levels of 18:2w6 in serum phospholipids, suggesting that an accelerated
      hepatic conversion of 18:2w6 to 20:4w6 occurs in HTPN patients, as well as the 20
      carbon members of w3 (20:3w3) and w9 (20:3w9) families. The determination of
      optimal parenteral fat intakes should be investigated further as important
      priority in patients receiving long term HTPN.

PMID- 12184518
TI  - High-fiber diet supplementation in patients with irritable bowel syndrome (IBS):
      a multicenter, randomized, open trial comparison between wheat bran diet and
      partially hydrolyzed guar gum (PHGG).
AB  - High-fiber diet supplementation is commonly used in IBS, although it poses
      several management problems. Partially hydrolyzed guar gum (PHGG) has shown
      beneficial effects in animal and human studies, but its potential role in IBS
      symptom relief has not been evaluated yet. We investigated PHGG in IBS patients
      and compared it to a wheat bran diet. Abdominal pain, bowel habits, and
      subjective overall rating were longitudinally evaluated in 188 adult IBS patients
      (139 women and 49 men) for 12 weeks. Patients were classified as having diarrhea
      predominant, constipation-predominant, or changeable bowel habits and were
      randomly assigned to groups receiving fiber (30 g/day of wheat bran) or PHGG (5
      g/day). After four weeks, patients were allowed to switch group, depending on
      their subjective evaluation of their symptoms. Significantly more patients
      switched from fiber to PHGG (49.9%) than from PHGG to fiber (10.9%) at four
      weeks. Per protocol analysis showed that both fiber and PHGG were effective in
      improving pain and bowel habits, but no difference was found between the two
      groups. Conversely, intention-to-treat analysis showed a significantly greater
      success in the PHGG group (60%) than in the fiber group (40%). Moreover,
      significantly more patients in the PHGG group reported a greater subjective
      improvement than those in the Fiber group. In conclusion, improvements in core
      IBS symptoms (abdominal pain and bowel habits) were observed with both bran and
      PHGG, but the latter was better tolerated and preferred by patients, revealing a
      higher probability of success than bran and a lower probability of patients
      abandoning the prescribed regimen, suggesting that it can increase the benefits
      deriving from fiber intake in IBS, making it a valid option to consider for high
      fiber diet supplementation.

PMID- 12184516
TI  - What the gastroenterologist should know about the gastrointestinal safety
      profiles of bisphosphonates.
AB  - Bisphosphonates are widely prescribed to treat Paget's disease of the bone and to
      prevent and treat osteoporosis. Soon after the release of alendronate,
      esophagitis and esophageal strictures were encountered, resulting in labeling
      changes. Subsequent endoscopic studies in normal subjects showed that alendronate
      also caused gastric erosions and ulcers. Although the clinical significance of
      these is still uncertain, the anatomic distribution of both the gastric ulcers
      and esophageal damage is consistent with a topical irritant effect. Recent data
      also suggest a synergistic ulcerogenic potential of concurrent alendronate and
      NSAID use. A 70-mg once-weekly dosage form of alendronate has recently been
      approved and clinical experience with its gastrointestinal tolerability is
      ongoing. Risedronate, a third-generation bisphosphonate, appears to have less
      ulcerogenic potential than alendronate, and esophageal stricture has not been
      reported. Experience with the bisphosphonates provide a paradigm for the critical
      role of endoscopists in evaluating the gastrointestinal profile of new drugs. As
      bisphosphonates are more widely prescribed and more types of bisphosphonates are
      developed, the role of the gastroenterologist is likely to assume even more
      importance.

PMID- 12184519
TI  - Resource utilization associated with irritable bowel syndrome in the United
      States 1987-1997.
AB  - This study uses national databases to examine the impact of irritable bowel
      syndrome (IBS) on resource utilization in the United States. Approximately 1.5
      2.7 million physician visits (599-1,043 per 100,000) yearly were related to IBS,
      with 45.3% seen by gastroenterologists, and 89% prescribed medications. Rates of
      physician visits by women were approximately 2.4-3.3 times higher than that for
      men. The average number of medication prescribed per visit was 1.83.
      Approximately 89% of the visits were prescribed with medications. The rate of
      hospitalization (5.1 per 100,000 in 1997) decreased by 60% and length of stay
      decreased from 5.5 to 3.1 days in the past decade. The average charges of IBS
      related hospitalization were US$7,882. Our study found an apparent decreasing
      trend of IBS-related hospitalizations and no marked increase in office
      consultations in the past decade. However, a better case identification criterion
      is necessary to estimate the true disease burden.

PMID- 12184520
TI  - Evidence for autonomic dysregulation in the irritable bowel syndrome.
AB  - Irritable bowel syndrome (IBS) is a common gastrointestinal disorder
      characterized by chronic abdominal pain and visceral hypersensitivity. In this
      study, resting blood pressure and heart rate were recorded in 20 IBS patients and
      23 controls. We assessed pain intensity and unpleasantness to visceral and
      cutaneous stimuli using rectal distension and immersion of the foot in hot water.
      Mean resting heart rate was higher in IBS patients compared to controls. IBS
      patients rated pain intensity and unpleasantness to visceral and cutaneous
      stimuli significantly higher than controls. In IBS patients, blood pressure was
      significantly inversely associated with visceral pain and only weakly and
      positively associated with cutaneous pain; there were no relationships in
      controls. Sex and anxiety did not explain these relationships. In conclusion, we
      found evidence suggestive of central autonomic dysregulation in IBS patients.

PMID- 12184521
TI  - Murine monoclonal anti-tNF antibody administration has a beneficial effect on
      inflammatory bowel disease that develops in IL-10 knockout mice.
AB  - Although the etiology of inflammatory bowel disease (IBD) is unknown, there is
      increasing evidence for the pivotal role played by tumor necrosis factor-alpha
      (TNF-alpha). Recent work has shown an increased concentration of TNF-alpha in
      both the bowel wall and in the stools of patients with IBD, and in children with
      that disease there are increased serum levels. Coincidental studies have shown
      that IL-10 knockout mice have increased levels of TNF-alpha and are known to
      develop a syndrome of stunted growth, anemia, bloody diarrhea, and colon tumors
      that mimics IBD. By injecting monoclonal antibodies intraperitoneally into IL-10
      knockout mice, we were able to demonstrate significant histologic improvement of
      inflammation that correlates well with a resolution of diarrhea and rectal
      bleeding. This finding is consistent with a role for anti-TNF-alpha in the
      pathogenesis of IBD and suggests that this model may be of use for examining the
      effects of anti-TNF-alpha antibody administration.

PMID- 12184523
TI  - Exogenous motilin affects postprandial proximal gastric motor function and
      visceral sensation.
AB  - Our aim was to investigate the effect of motilin on postprandial proximal gastric
      motor and sensory function in healthy volunteers. Ten fasted, healthy volunteers
      were infused intravenously with synthetic motilin or placebo over 90 min. A
      liquid meal (200 ml) was ingested within 2 min at the start of the infusion.
      Proximal gastric volume was measured with a barostat device. Abdominal symptoms
      were scored by visual analog scales. Plasma motilin concentrations were measured
      using RIA. Endogenous motilin levels were not affected by meal ingestion. After
      meal intake, gastric relaxation was similar for motilin and placebo. After
      postprandial relaxation, motilin resulted in a faster return of gastric volume to
      baseline (P = 0.007). Motilin significantly increased postprandial feelings of
      nausea (P = 0.03) and tended to increase abdominal pain and abdominal tension. In
      conclusion, after normal postprandial gastric relaxation, motilin accelerated the
      return of gastric volume to baseline. In addition, motilin increased postprandial
      feelings of nausea.

PMID- 12184522
TI  - Crohn's disease complicated by a urachoenteric fistula.

PMID- 12184524
TI  - Changes in gastric myoelectric activity during space flight.
AB  - The purpose of the present study was to examine postprandial myoelectric activity
      of the stomach and gastric activity associated with space motion sickness using
      electrogastrography. Three crewmembers participated in this investigation.
      Preflight, subjects exhibited normal postprandial responses to the ingestion of a
      meal. Inflight, crewmembers exhibited an abnormal decrease in the power of the
      normal gastric slow wave after eating on flight day 1, but had a normal
      postprandial response by flight day 3. Prior to and during episodes of nausea and
      vomiting, the electrical activity of the stomach became dysrhythmic with 60-80%
      of the spectral power in the bradygastric and tachygastric frequency ranges.
      These findings indicate that gastric motility may be decreased during the first
      few days of space flight. In addition, changes in the frequency of the gastric
      slow wave associated with space motion sickness symptoms are consistent with
      those reported for laboratory-induced motion sickness.

PMID- 12184525
TI  - Impaired gastric slow wave rhythmicity in patients after bone marrow or stem cell
      transplant.
AB  - Patients after bone marrow or stem cell transplant often develop gastrointestinal
      symptoms. The aim of this study was to investigate possible impairment of gastric
      myoelectrical activity in these patients. The study was performed in 15 patients
      who had had bone marrow or stem cell transplant and 13 healthy subjects. Gastric
      myoelectrical activity was assessed using electrogastrography. The
      electrogastrogram (EGG) was made for 30 min in the fasting state and 60 min after
      a test meal (475 kcal; turkey sandwich). Overall and minute-by-minute spectral
      analyses were performed to derive various parameters of the EGG. Compared with
      the healthy controls, the patients showed a significantly higher percentage of
      arrhythmia (no obvious rhythmicity observed in the EGG) in both fasting (17.6 +/-
      3.8% vs 7.1 +/- 2.17%, P < 0.02) and fed (11.4 +/- 2.65% vs 4.19 +/- 1.04%, P <
      0.02) state. The patients showed a significantly higher instability coefficient
      of the dominant frequency in the fasting state than in the controls (0.51 +/-
      0.06 vs 0.29 +/- 0.18, P < 0.008). The total average symptom score was 3.93 +/-
      0.84 in the patients and 0 in the controls, and a relatively weak but significant
      correlation was found between the symptom scores and the percentage of arrhythmia
      in the patients in fed state (r = 0.69, P < 0.02). It was concluded that patients
      with bone marrow or stem cell transplant have excessive arrhythmia that is
      correlated with their dyspeptic symptoms.

PMID- 12184526
TI  - Extrinsic denervation causes a transient proabsorptive adrenergic
      hypersensitivity in the canine proximal colon.
AB  - Our aim was to determine if extrinsic denervation alters the absorptive response
      of the colon to proabsorptive and prosecretory stimuli. Ten dogs underwent
      enteric isolation of a 50-cm proximal colonic segment; five were also randomized
      to undergo extrinsic denervation (DEN). At 2 and 13 wk postoperatively, net
      absorptive fluxes (mean +/- SEM) of water and electrolytes were determined during
      basal conditions and during proabsorptive low-dose (0.3 microg/kg/min) or high
      dose (3 microg/kg/min) norepinephrine or prosecretory VIP (500 pg/kg/min). The
      net absorptive flux of water under basal conditions was decreased in DEN versus
      neurally intact controls at two weeks (4.0 +/- 0.6 vs 6.6 +/- 0.7 microl/min/cm,
      P = 0.03) but did not differ at 13 weeks (5.0 +/- 1.0 vs 5.7 +/- 0.9, P > 0.05).
      Low- and high-dose norepinephrine increased water absorption in both groups at
      two weeks; the change in flux for high-dose norepinephrine was greater in DEN
      versus controls (4.1 +/- 1 vs 2.1 +/- 0.6 microl/min/cm, P = 0.04). Net
      absorptive fluxes of Na+ and Cl- followed these trends. VIP did not alter
      absorption of water or electrolytes. Extrinsic denervation of the proximal colon
      causes a decrease in net colonic absorption and a transient, proabsorptive
      adrenergic hypersensitivity in colonic absorption of water and electrolytes. VIP
      does not have a net secretory effect in the proximal canine colon.

PMID- 12184527
TI  - Cystic fibrosis transmembrane conductance regulators (CFTR) in biliary epithelium
      of patients with hepatolithiasis.
AB  - Cystic fibrosis transmembrane conductance regulator (CFTR) has been considered to
      be involved in the regulatory pathway of biliary mucin secretion. We investigated
      expression of CFTR protein and mRNA in 24 livers with hepatolithiasis, in 6 with
      cholangiocarcinoma, and in 12 histologically normal livers. According to the
      histologic features of chronic proliferative cholangitis, hepatolithiasis was
      subdivided into inflammatory cell infiltration predominant (N = 14) and fibrosis
      predominant (N = 10). The mean signal density of CFTR in overall hepatolithiasis
      and in histologically normal livers was 1.23 +/- 0.15 and 1.01 +/- 0.13,
      respectively (P > 0.05). The CFTR protein (1.60 +/- 0.18) and mRNA (1.09 +/-
      0.15) in inflammatory cell infiltration predominant patients were significantly
      higher (CFTR protein, 1.01 +/- 0.13; mRNA, 0.75 +/- 0.11) than in control
      subjects (P < 0.05), whereas those in fibrosis-predominant patients (CFTR
      protein, 0.72 +/- 0.15; mRNA, 0.55 +/- 0.13) were less than in control subjects
      (P < 0.05). CFTR protein (1.27 +/- 0.17) in patients with cholangiocarcinoma was
      not different from that of control subjects (1.01 +/- 0.13). CFTR expression in
      hepatolithiasis patients was rather heterogeneous but was closely related to the
      histology of bile ducts.

PMID- 12184528
TI  - Neutral endopeptidase activity is not elevated in serum in children with
      cholestatic liver disease: a unique role of aminopeptidase-m in sequential
      hydrolysis of peptides.
AB  - The aim of this study was to determine whether neutral endopeptidase activity is
      elevated in serum in children with cholestatic liver disease (Alagille syndrome),
      and whether the enzyme cooperates with the serum aminopeptidase-M in degradation
      of peptides. Our data suggest that neutral endopeptidase activity remains at a
      very low level,.undetectable with the assays we have applied, both in the serum
      from healthy children and those with cholestasis. In contrast, the serum
      aminopeptidase-M activity is highly increased in cholestasis. We have
      demonstrated that aminopeptidase-M alone is capable of sequential and complete
      hydrolysis of enkephalins and low-molecular-weight, nonspecific peptides. The
      rate of release of free amino acids from both exogenous or endogenous substrate
      peptides was statistically significantly higher in serum in children with
      cholestasis compared with healthy children (P < 0.05). Substance P (Ki = 2.5
      micromol/liter) and bradykinin (Ki = 27 micromol/liter) were shown to be potent
      inhibitors of the serum aminopeptidase-M. We postulate that aminopeptidase-M,
      except when regulating the activity of bioactive peptides, may serve as a
      scavenger of short, nonspecific peptides in the circulation. Our data seem to
      provide new insights for further studies on the role of serum peptidases both in
      physiology and pathophysiology.

PMID- 12184529
TI  - Effects of glycyrrhizin on glucocorticoid signaling pathway in hepatocytes.
AB  - The cytoprotective effects of glycyrrhizin (GL) are similar to glucocorticoids.
      We investigated the effects of GL on the glucocorticoid receptor (GR) and on the
      enzyme activity of tyrosine aminotransferase (TAT), an hepatocyte-specific marker
      of glucocorticoid action, in rat hepatocytes. Pretreatment with GL significantly
      decreased the affinity of GRs for dexamethasone (DEX) and increased the period of
      time required for TAT activity to reach a peak after the addition of DEX. GL did
      not affect the amount of GR, but significantly decreased the amount of heat-shock
      protein 90 (HSP90) and HSP90-associated GR. Alternatively, TAT activity and TAT
      mRNA levels increased significantly after the addition of GL to hepatocytes
      pretreated with DEX. In conclusion, GL reduces the affinity of GRs for ligands
      through the decreased HSP90 expression, but significantly enhances the
      glucocorticoid-induced TAT-gene expression at the transcriptional level in rat
      hepatocytes.

PMID- 12184530
TI  - Remission of severe aplastic anemia associated with hepatitis B virus infection
      after viral clearance: potential role of lamivudine.
AB  - Although viral hepatitis infection is known to be associated with aplastic
      anemia, a causal link between viral hepatitis and aplastic anemia has not been
      convincingly demonstrated. A case of hepatitis B-associated severe aplastic
      anemia is described which only partially responded to conventional
      immunosuppressive treatment but went into complete clinical remission after
      clearance of the hepatitis B virus. Disappearance of the hepatitis B virus
      occurred during lamivudine treatment and coincided with immune activation
      secondary to discontinuation of immunosuppressive therapy. This case was somewhat
      atypical in that a history of acute hepatitis preceding the aplastic anemia was
      absent. The observation made in this case report supports a cause-effect
      relationship between hepatitis B virus infection and aplastic anemia.

PMID- 12184531
TI  - Endothelin content, expression, and receptor type in normal and diseased human
      gallbladder.
AB  - The aims of this study were to characterize the endothelin (ET) system in human
      gallbladder by determining (1) the tissue content of ET-1 and ET-2 by ELISA; (2)
      the expression of mRNA of the ET precursors preproendothelin-1, -2, and -3; and
      (3) mRNA expression for the ETA and ETB receptors. Median content of ET-1/2 was
      significantly reduced in severely inflamed gallbladders compared to gallbladders
      with mild inflammation. There was an inverse correlation between content of ET
      1/2 and inflammation score. mRNA for preproendothelin-2 was highly expressed in
      all samples, whereas mRNA for preproendothelin-1 was present in negligible
      quantities and mRNA for preproendothelin-3 was undetectable. mRNA for ETA
      receptors was expressed in all samples analyzed, whereas mRNA for ETB receptors
      was expressed at a much lower level. This study demonstrates the presence of ET
      1/2 in human gallbladder. ET-1/2 content is decreased with increasing degrees of
      histological inflammation. ET-2 is likely to be the physiologically significant
      endothelin isopeptide expressed and ETA receptors appear to predominate in the
      human gallbladder.

PMID- 12184532
TI  - Glutathione depletion with L-buthionine-(S,R)-sulfoximine demonstrates
      deleterious effects in acute pancreatitis of the rat.
AB  - A common pathway in the pathogenesis of acute pancreatitis is the generation of
      free oxygen radicals. The most important defense mechanisms are free radical
      scavengers, especially glutathione. This study evaluates the influence of the
      inhibition of glutathione synthesis with L-buthionine-(S,R)-sulfoximine (BSO) on
      the course of experimentally induced acute pancreatitis in rats and the effects
      on isolated pancreatic acini and their secretion pattern. Thus acute necrotizing
      pancreatitis was induced with intraductal infusion of low-dose glycodeoxycholic
      acid and subsequent hyperstimulation with cerulein with and without pretreatment
      with BSO. In vitro pancreatic acini were isolated and stimulated with different
      concentrations of cerulein with and without BSO. The BSO-treated group showed a
      significantly reduced survival, more necrosis, and a decreased secretion of
      amylase in vivo. No effect on secretion pattern in either groups was seen in
      vitro and BSO did not exert toxic effects. Based on the data presented, this
      study demonstrates deleterious effects of scavenger depletion on the course of
      experimental pancreatitis. This is due to the systemic effects of free oxygen
      radicals rather than to local effects.

PMID- 12184533
TI  - Cholecystokinin antagonist L364,718 induces alterations in acinar cells that
      prevent improvement of acute pancreatitis induced by obstruction.
AB  - The aim of this study was to examine the effect of the most potent CCK receptor
      antagonist, L364,718, on two major factors involved in pancreatitis development:
      enzyme load and cytosolic calcium (Ca2+) levels in acinar cells. L364,718 (0.1
      mg/kg/12 hr) was administered from 30 min before inducing acute pancreatitis (AP)
      by pancreatic duct obstruction (PDO) for 48 hr. The results obtained at different
      AP stages in PDO rats treated and not treated with the CCK antagonist were
      compared. Similar increases in the intracellular enzyme content were found at
      earlier stages of pancreatitis in all PDO rats treated or not treated with
      L364,718. The CCK antagonist increased cytosolic Ca2+ levels up to 6 hr after
      administration, inducing a higher cytosolic Ca2+ overload at the earliest stages
      of pancreatitis in L364,718-treated PDO rats than in those not treated. This
      event might justify the higher increases in ascites volume and haematocrit found
      in PDO rats treated with L364,718 and the exacerbation in pancreatic
      morphological alterations induced by PDO. The CCK receptor antagonist L364,718
      produces alterations in the acinar calcium homeostasis that prevent to reduction
      in the severity of pancreatitis induced by obstruction.

PMID- 12184534
TI  - Bile duct involvement in a case of autoimmune pancreatitis successfully treated
      with an oral steroid.
AB  - In the case reported here, the characteristic features of AIP were evaluated by
      ultrasonography, computed tomography and endoscopic retrograde
      cholangiopancreatography, initially in the intrahepatic- and extrahepatic bile
      ducts, and later in the pancreas. In addition, histological examination revealed
      lymphocytic sclerosis around the intralobular bile ducts, as is reported in AIP,
      without chronic nonsuppurative destructive cholangitis or onion-skin-like
      appearance. Immunohistochemistry identified the infiltrating lymphocytes as T
      cells. Although hypergammaglobulinemia was observed with elevation of
      hepatobiliary and pancreatic enzymes, no other serological or physiological
      abnormalities suggestive of other systemic autoimmune diseases were detected.
      These findings progressed over a three-month period and were dramatically
      resolved within one month by steroid therapy. These observations support a novel
      clinical entity characterized by the presence of bile duct lesions similar to the
      pancreatic involvement seen in AIP that is distinct pathophysiologically,
      histologically, and therapeutically from the so-called autoimmune cholangitis or
      primary sclerosing cholangitis.

PMID- 12184535
TI  - Clinical features of ciliated foregut cyst of the gallbladder: a rare entity of
      cystic lesion in the gallbladder.

PMID- 12184537
TI  - Expression of maspin in colon cancers: its relationship with p53 expression and
      microvessel density.
AB  - We studied the expression of maspin in colonic adenocarcinoma compared with
      adenoma and metastatic adenocarcinoma as well as the relationship with its
      possible regulator, p53. The colonic specimens consisted of 24 adenomas, 49
      adenocarcinomas, and 17 metastatic adenocarcinomas. Immunohistochemical staining
      of paraffin sections was done with microwave-based antigen retrieval methods. The
      Ki-67 index and the microvessel density were counted using an image analysis
      system. Maspin expression was positive in 75.5% of adenocarcinomas and 91.7% of
      adenomas. Only 47.1% of the nodal metastasis showed positive maspin expression.
      In colonic adenocarcinomas, p53 expression was positive in 44.7% of the maspin
      positive groups compared with 100% of the maspin-negative groups (P < 0.005).
      Colonic adenocarcinomas with the positive maspin expression groups showed less
      intense microvessel density (181.1 +/- 54.2) than those of the negative maspin
      expression groups (256.1 +/- 75.4,P < 0.001). In conclusion, we demonstrated
      maspin expression in colon cancer with a sequential decreased expression rate
      from adenoma to metastatic carcinomas, which signifies the tumor suppressive
      function of maspin, and an inverse correlation with p53 and microvessel density,
      which indicates the regulatory effect of p53 on maspin and anti-angiogenesis
      effect of maspin.

PMID- 12184538
TI  - Pancreatic cancer with chylous ascites demonstrated by lymphoscintigraphy:
      successful treatment with peritoneovenous shunting.
AB  - A 60-year-old woman was admitted to our hospital because of abdominal distension
      caused by massive chylous ascites. Six months earlier, she was diagnosed with
      inoperative pancreatic head cancer and biliary tract stenting and radiation
      therapy were performed due to obstructive jaundice. The chylous ascites was
      observed by lymphoscintigraphy with 99mTc-labeled human serum albumin. It showed
      upper abdomen accumulation and leakage into the abdominal cavity, and a diagnosis
      of chylous ascites caused by obstruction or rupture of lymphocele due to
      pancreatic cancer was made. Chylous ascites did not improve with a conservative
      therapy, including low-fat diet and administration of flousemide, but was
      successfully treated with a peritoneovenous shunt using a Denver shunting tube.
      In association with the placement of the shunt, she lived for 15 months after the
      first diagnose of pancreatic cancer without pancreatoduodenectomy.

PMID- 12184536
TI  - Balance between activation and inhibition of matrix metalloproteinase-2 (MMP-2)
      is altered in colorectal tumors compared to normal colonic epithelium.
AB  - Matrix metalloproteinase-2 (MMP-2) is overexpressed in human cancers and
      facilitates tumor growth and metastasis. It is synthesized as an inactive
      proenzyme that is activated by membrane-type matrix metalloproteinase-1 (MT1-MMP)
      and inhibited by tissue inhibitor of metalloproteinase-2 (TIMP-2). We
      hypothesized that there is an imbalance between the expression of TIMP-2 and the
      expression of MMP-2 and MT1-MMP that favors activation of MMP-2 in malignant
      colon tumors compared to normal colonic tissue. Specimens of colon tumors and of
      adjacent normal mucosa were obtained from 22 patients at the time of surgical
      resection. MMP-2, MT1-MMP, and TIMP-2 RNA transcripts were measured in each
      sample using a quantitative reverse transcriptase polymerase chain reaction
      assay. We observed that MMP-2 RNA levels were significantly elevated in tumors
      compared to normal tissue (P = 0.039). In addition, the TIMP-2:MMP-2 ratio was
      twofold lower (P = 0.001) and the TIMP-2:MT1-MMP ratio was 1.5-fold lower (P =
      0.003) in tumors compared to normal mucosa. These results suggest that the
      balance between genes that activate and inhibit MMP-2 is shifted toward
      activation in colon tumors. The abnormal expression of gene products that
      regulate MMP-2 activity may be an important early step in the malignant
      transformation of colon cancer and may provide a useful target for new
      chemoprevention and adjuvant treatment strategies.

PMID- 12184539
TI  - Multiple late asymptomatic pancreatic metastases from renal cell carcinoma:
      diagnosis by endoscopic ultrasound-guided fine needle aspiration biopsy with
      immunocytochemical correlation.
AB  - We describe a patient who presented with multiple asymptomatic masses detected in
      the pancreas. Twelve years prior to this presentation, he underwent a left
      radical nephrectomy for stage I renal cell carcinoma. CT-guided biopsy was
      unsuccessful. Endoscopic ultrasound guided fine needle aspiration (EUS-FNA)
      biopsy was performed. Adequate material was obtained for various
      immunocytochemical stains that supported the diagnosis of renal cell carcinoma
      metastatic to the pancreas. The patient was referred for appropriate therapy.
      This case illustrates that metastasis to the pancreas from renal cell carcinoma
      can present years after the original diagnosis. We conclude that EUS-FNA can
      provide tissue diagnosis from pancreatic masses, especially when other modalities
      have failed.

PMID- 12184540
TI  - Measurement of postprandial changes in urine acid output to detect changes of
      gastric acid secretion after proton pump inhibitors in children.
AB  - Acid inhibition after proton pump inhibitors in children is variable, and to
      measure it by a noninvasive method may help to tailor treatment. To study gastric
      acid inhibition after a single dose of PPI, by measuring urinary acid output
      (UAO), which decreases as parietal cells release acid into the stomach during a
      meal, we performed a prolonged pH monitoring in 31 children (age range 3-16 yrs).
      Esophageal and intragastric pH was recorded for 24 hr and for 5 more hr after a
      single dose of PPI or placebo. Urine was collected early in the morning, and 1 hr
      after a test meal. Intragastric and urinary parameters were analyzed for 5 hr
      after PPI and compared to the same 5 hr at baseline. After PPI, median gastric pH
      significantly increased, and median AUAO became significantly smaller (-0.31 vs. 
      1.40 at baseline; P = 0.002) but was unchanged after placebo. Inhibition of
      gastric acid induced by PPI can be detected by changes in UAO and its
      determination may be useful to monitor the PPI effect.

PMID- 12184542
TI  - Helicobacter pylori prevents proliferative stage of angiogenesis in vitro: role
      of cytokines.
AB  - Inhibition of angiogenesis may explain the delayed ulcer healing following
      Helicobacter pylori infection. We have previously demonstrated that H. pylori can
      inhibit endothelial cell proliferation. Some cytokines possess antiangiogenic
      properties. This study assessed a role for IL-6, IL-8, and TNF-a in H. pylori
      induced endothelial cytostasis. First, 30 microl of H. pylori was coincubated
      with microvascular endothelial cells in the presence or absence of monoclonal
      antibodies to IL-6, IL-8, and TNF-a for 24, 48, 72, or 96 hr. Dual labeling with
      propidium iodide and Hoescht 33342 distinguished between necrosis, and apoptosis
      and allowed viable cell numbers to be determined. H. pylori decreased cell
      viability after 72 and 96 hr (P < 0.02). Neither necrosis nor apoptosis was
      observed. Monoclonal antibodies to IL-6 and IL-8 did not reverse cytostasis.
      However, significant MVEC proliferation was observed in the presence of the TNF-a
      monoclonal antibody. In conclusion, H. pylori induces cytokine up-regulation as
      part of its pathophysiological mechanism, which could prove detrimental to ulcer
      healing through an inhibitory effect on angiogenesis.

PMID- 12184544
TI  - Dynamic position versus 24-hour pH testing for detection of esophageal acid
      reflux disease.
AB  - Although the 24-hour pH test is currently considered the gold standard for the
      determination of significant esophageal acid reflux disease, it is a problematic
      study, requiring multiple manipulations for interpretation. Dynamic position
      testing has recently been described as an alternative method of detecting
      significant esophageal acid reflux disease. In this initial comparative study,
      dynamic position testing was at least as reliable as 24-hour pH testing, required
      much less time, and provided additional useful information.

PMID- 12184541
TI  - Comparison of cytotoxin genotypes of Helicobacter pylori in stomach and saliva.
AB  - We have previously reported a high prevalence of H. pylori DNA in saliva. In this
      study, the cytotoxin genotypes of H. pylori strains from both stomach and saliva
      were compared in 31 patients with gastritis and peptic ulcer. The cagA, vacA m1,
      vacA m2, and vacA s1 genotypes were analyzed by PCR. The 417 bp PCR products from
      three patients were also subjected to DNA sequencing analysis. There was 95%
      agreement between stomach H. pylori isolates and their corresponding saliva DNA
      in at least one cytotoxin genotype; 86% agreement with two cytotoxin genotypes;
      59% agreement with three cytotoxin genotypes; and 27% agreement with all four
      cytotoxin genotypes studied. DNA sequencing from three patients showed 78.0%,
      64.0%, and 66.9% homology of H. pylori from both sources, respectively. The data
      suggest that more than one H. pylori strain may exist in the stomach and saliva
      in the same patient.

PMID- 12184543
TI  - Identifying patients with gastroesophageal reflux disease: validation of a
      practical screening tool.
AB  - A reliable, accurate noninvasive method for identifying patients with
      gastroesophageal reflux disease (GERD) in the primary care setting is needed. A
      population-based case-finding instrument may assist managed care organizations in
      identifying candidates for disease management or quality improvement programs.
      Our aim was to develop and validate a GERD case-finding instrument. A 12-item
      "GERD Screener" was developed based on literature review and expert opinion with
      questions about heartburn and regurgitation frequency and severity and medication
      use, as well demographics and exclusion criteria. Categorical and continuous
      scoring methods with and without medication use were developed a priori. Using a
      telephone interview in a medical group, we identified and enrolled 100 subjects
      with a history of GERD-like symptoms and 103 controls. Each subject completed the
      GERD Screener, a validated gastrointestinal symptom questionnaire, the Digestive
      Health Symptom Index (DHSI), and was evaluated independently by two
      gastroenterologists using a structured format. Agreement by the two physicians
      that symptoms were consistent with GERD and required an intervention was
      considered the gold standard. In all, 70 subjects were classified as having GERD
      and 106 as controls using the gold standard (K = 0.73; 95% CI, 0.63-0.82). The
      scoring method for the screening instrument using a continuous measure of GERD
      symptoms (frequency and severity) and weighted medication use resulted in an area
      under ROC of 0.89 (95% CI, 0.84-0.94). Using a cutoff of >9 points, this measure
      was 83% sensitive and 83% specific. Compared to the gold standard, the DHSI GERD
      subscale has an area under ROC of 0.89 (95% CI, 0.84-0.94). The GERD Screener was
      highly correlated with the DHSI GERD subscale, r = 0.78 (95% CI 0.72-0.83; P <
      0.0001). In conclusion, the GERD Screener has demonstrated construct, convergent,
      and predictive validity. It is shorter than existing validated instruments,
      practical, and easily administered, which may reduce the response and
      administrative burden. This may serve as a valuable case-finding instrument in
      primary-care and managed-care organizations wishing to implement programs to
      improve the quality and efficiency of care.

PMID- 12184545
TI  - Analysis of mucosal stress response in acid-induced esophagitis in opossum.
AB  - This study is the first to examine site-specific changes in mucosal antioxidants
      and expression and localization of heat shock proteins (HSPs) following the
      induction of subacute esophagitis and after recovery using an established animal
      model. Distal, middle, and proximal samples were excised from anesthetized
      opossums 24 hr after three consecutive days of 45-min perfusion with saline or
      100 mmol/liter HCI, or seven days after acid in recovery animals. Compared to
      controls, acid-induced erosive esophagitis significantly increased glutathione
      peroxidase and HSP90 at all sites and HSP60 proximally. Reduced glutathione was
      significantly decreased distally, as was HSP72 at distal and middle sites. No
      changes in superoxide dismutase or catalase occurred. After recovery, superoxide
      dismutase, catalase, and HSP expression were not different from controls.
      Glutathione peroxidase and glutathione were significantly decreased distally.
      Similar differential stress responses may occur in patients with chronic
      gastroesophageal reflux and could be important in the pathogenesis of reflux
      esophagitis.

PMID- 12184546
TI  - Early phase metabolic bone disorders after gastrectomy: influence of active
      vitamin D treatment.
AB  - Metabolic bone disorders are recognized as one of the late complications after
      gastrectomy. However, the onset time and the extent of bone disorders are still
      unknown. We examined the influence of active vitamin D treatment on bone
      metabolism in the early period after gastrectomy. Sixty-three postgastrectomy
      patients were divided into two groups; active vitamin D treatment group [VD(+)]
      and no treatment group [VD(-)]. The level of serum calcium and phosphate was
      increased in the VD(+) group compared with the preoperative level, and
      parathyroid hormone (PTH-M) was decreased in the VD(+) group. Both 1,25-(OH)2D3
      and bone-specific alkaline phosphatase (B-ALP) were increased in the VD(-) group.
      Cross-linked carboxyterminal telopeptide of type I collagen (I-CTP) was increased
      in the VD(+) group. There was no change in calcitonin in either group. In
      conclusion, metabolic bone disorders after gastrectomy have their onset in the
      early period, and active vitamin D treatment from the early period may be
      effective in preventing bone disorders.

PMID- 12184548
TI  - Barrett's esophagus-associated polypoid dysplasia: a case report and review of
      the literature.

PMID- 12184547
TI  - Duodenogastric bile reflux after gastric bypass: a cholescintigraphic study.
AB  - In this exploratory study, we examined the occurrence of duodenogastric bile
      reflux to the excluded stomach after Roux-en-Y gastric bypass, a standard
      surgical therapy for morbid obesity. We studied 22 unselected patients (median
      age 44, 20 females) 18 months postoperatively. BMI at surgery and
      cholescintigraphy was 45 and 29 kg/m2, respectively. Mebrofenin labeled with 200
      MBq 99mT was injected intravenously and the fate of radioactivity followed for 90
      min. Bile flow was enhanced with cholecystokinin. We found scintigraphic evidence
      of duodenogastric bile reflux in 36% of the patients. The tracer remained in the
      excluded stomach throughout the study period. In conclusion, our investigation
      indicates that in more than one third of the patients undergoing gastric bypass,
      the gastric mucosa in the excluded stomach is exposed to the potential
      deleterious effects of bile.

PMID- 12184549
TI  - Sexually transmitted diseases treatment guidelines 2002. Centers for Disease
      Control and Prevention.
AB  - These guidelines for the treatment of patients who have sexually transmitted
      diseases (STDs) were developed by the Centers for Disease Control and Prevention
      (CDC) after consultation with a group of professionals knowledgeable in the field
      of STDs who met in Atlanta on September 26-28, 2000. The information in this
      report updates the 1998 Guidelines for Treatment of Sexually Transmitted Diseases
      (MMWR 1998;47 [No. RR-1]). Included in these updated guidelines are new
      alternative regimens for scabies, bacterial vaginosis, early syphilis, and
      granuloma inguinale; an expanded section on the diagnosis of genital herpes
      (including type-specific serologic tests); new recommendations for treatment of
      recurrent genital herpes among persons infected with human immunodeficiency virus
      (HIV); a revised approach to the management of victims of sexual assault;
      expanded regimens for the treatment of urethral meatal warts; and inclusion of
      hepatitis C as a sexually transmitted infection. In addition, these guidelines
      emphasize education and counseling for persons infected with human
      papillomavirus, clarify the diagnostic evaluation of congenital syphilis, and
      present information regarding the emergence of quinolone-resistant Neisseria
      gonorrhoeae and implications for treatment. Recommendations also are provided for
      vaccine-preventable STDs, including hepatitis A and hepatitis B.

PMID- 12184550
TI  - Outline shape is a mediator of object recognition that is particularly important
      for living things.
AB  - We assess the importance of outline shape in mediating the recognition of living
      and nonliving things. Natural objects were presented as shaded line drawings or
      silhouettes, and were living and nonliving things. For object decision (deciding
      whether an object may be encountered in real life) there were longer response
      times to nonliving than to living things. Importantly, this category difference
      was greater for silhouettes than for shaded line drawings. For naming, similar
      category and stimulus differences were evident, but were not as pronounced. We
      also examined effects of prior naming on subsequent object decision performance.
      Repetition priming was equivalent for nonliving and living things. However, prior
      presentation of silhouettes (but not shaded line drawings) reduced the longer RT
      to nonliving things relative to living things in silhouette object decision. We
      propose that outline contour benefits recognition of living things more than
      nonliving things: For nonliving things, there may be greater 2-D/3-D
      interpretational ambiguity, and/or they may possess fewer salient features.

PMID- 12184551
TI  - Effects of plane rotation, task, and complexity on recognition of familiar and
      chimeric objects.
AB  - We examined the effects of plane rotation, task, and visual complexity on the
      recognition of familiar and chimeric objects. The effects of rotation, with
      response times increasing linearly and monotonically with rotation from the
      upright, were equivalent for tasks requiring different degrees of visual
      differentiation of the target from contrasting stimuli--namely, (1) deciding
      whether the stimulus was living or nonliving (semantic classification), (2)
      deciding whether the stimulus was an object or a nonobject (object decision), and
      (3) naming. The effects of complexity, with shorter response times to more
      complex stimuli, were most apparent in semantic classification and object
      decision and were additive with the effects of rotation. We discuss the
      implications of these results for theories of the relationship between the
      process of normalization and the determining of object identity.

PMID- 12184552
TI  - Proust nose best: odors are better cues of autobiographical memory.
AB  - The Proust phenomenon is an enduring piece of folk wisdom that asserts that odors
      are particularly powerful autobiographical memory cues. We provide a more formal
      exposition of this phenomenon and test it in two experiments, using a novel
      double-cuing methodology designed to negate less interesting explanations. In
      both studies, recall of an autobiographical event was initially cued by a verbal
      label (an odor name) for a fixed period, following which a second, extended
      recall attempt was cued by the same verbal label, the relevant odor, an
      irrelevant odor, or a visual cue. The focus of Experiment 1 was participants'
      ratings of the emotional quality of their autobiographical memories. In
      Experiment 2, content analysis was employed to determine the quantity of
      information in participants' recollections. Results revealed that odor-cued
      autobiographical memories were reliably different in terms of qualitative ratings
      and reliably superior in the amount of detail yielded. Moreover, visual cues and
      incongruent olfactory cues appeared to have a detrimental effect on the amount of
      detail recalled. These results support the proposal that odors are especially
      effective as reminders of past experience.

PMID- 12184553
TI  - Phenomenal characteristics of guided imagery, natural imagery, and
      autobiographical memories.
AB  - Research indicates that guided imagery experiences can be mistaken for actual
      experiences under some circumstances. One explanation for such effects is that
      memory representations of guided imagery and actual events contain similar
      phenomenal characteristics such as sensory and contextual details, making the
      source of the events less distinguishable. This study examined this prediction,
      comparing memory characteristic ratings for guided imagery experiences with those
      for memories of perceived and natural imagery events (e.g., fantasies). Results
      replicated previous findings for the difference between perceived and natural
      imagery memories. Guided imagery ratings were also lower than those for perceived
      memories for most sensory details (sound, smell, and taste) and temporal details.
      However, guided imagery ratings for reflective details were lower than both
      perceived and natural imagery memory ratings. Thus, guided imagery was similar to
      natural imagery with respect to sensory details, but similar to perceived
      memories with respect to reflective details.

PMID- 12184554
TI  - Eliminating the cost of task set reconfiguration.
AB  - With insufficient time to fully prepare for a switch in task, a deterioration in
      performance on the first trial of a new task would be expected. The interest of
      researchers has been captured by the residual switch costs that, surprisingly,
      remain despite sufficient time to prepare. We used avery simple task to
      investigate the costs to reaction time and accuracy associated with changing
      between two different instructional sets every eight trials. Subjects responded
      to left and right visual targets by making either spatially compatible or
      incompatible eye movements (Experiment 1) or buttonpress responses (Experiment
      2). The subjects were cued as to whether to make the compatible or the
      incompatible response by the color of a border appearing on the perimeter of the
      display. In cases in which the subject alternated between making pro- and
      antisaccades, the large costs to reaction time and accuracy at the short cue
      target stimulus onset asynchrony were completely eliminated when sufficient time
      was provided to prepare for the switch. This complete elimination of residual
      switch costs was not obtained when the same alternation was applied to manual
      responses. This pattern of results links residual costs to response selection
      processes and suggests that they are not a necessary component of the switch
      process. We propose that the elimination of "stubborn" residual switch costs is
      rooted in our use of a hypercompatible task (making saccades toward targets) that
      places minimal demands on response selection.

PMID- 12184555
TI  - Limitations in advance task preparation: switching the relevant stimulus
      dimension in speeded same-different comparisons.
AB  - When participants switch between relevant stimulus dimensions in speeded
      classification tasks, task-switching cost is reduced by advance preparation.
      Previous studies in which speeded classification tasks were used have suggested
      that this effect results from attending to the relevant stimulus dimension.
      Because selective attention to the relevant stimulus dimension in same-different
      judgments is relatively poor (e.g., Santee & Egeth, 1980), it was predicted that
      advance task preparation for a shift in the relevant stimulus dimension would be
      compromised. This prediction was borne out in two experiments comparing dimension
      shifts (shape vs.fill) with task rule shifts (same? vs. different? and shifts in
      the mapping of right-left keys to yes and no responses (yes-no vs. no-yes). The
      results indicate that advance attentional selection of the relevant dimension is
      an optional preparatory strategy in task switching, employed only in conditions
      enabling flexible refocusing of attention.

PMID- 12184556
TI  - Overt reanalysis strategies and eye movements during the reading of mild garden
      path sentences.
AB  - In an eye movement experiment, we examined the use of reanalysis strategies
      during the reading of locally ambiguous but globally unambiguous Spanish
      sentences. Among other measures, we examined regressive eye movements made while
      readers were recovering in reading mild garden path sentences. The sentences had
      an adverbial clause that, depending on the mood (indicative vs. subjunctive) of
      the subordinate clause verb, could attach high (to the main verb of the sentence)
      or low (to the verb in the subordinate clause). Although Spanish speakers favor
      low attachment, the high attachment version was quite easy to understand. Readers
      predominately used two alternative strategies to recover from the mild garden
      path in our sentences. In the more common reanalysis strategy, their eyes
      regressed from the last region (disambiguation+ 1) directly to the main verb in
      the sentence. Following this, they reread the rest of the sentence, fixating the
      next region and the adverb (the beginning of the ambiguous part of the sentence).
      Less frequently, readers regressed from the last region (disambiguation+1)
      directly to the adverb. We argue that both types of strategies are consistent
      with a selective reanalysis process as described by Frazier and Rayner (1982).

PMID- 12184557
TI  - Effect of focus on verbal working memory: critical role of the focus word in
      reading.
AB  - The effect of focus on working memory was investigated with the reading span test
      (RST). In two experiments, the span scores and the number of intrusion errors
      were compared between the focused RST the and the nonfocused RST. Focus word was
      defined as the most important word for comprehending a sentence. For the focused
      RST, the target word to be maintained was the focus word for the sentence. In the
      nonfocused RST, however, the target word was not the focus word for the sentence.
      The results of both experiments showed that RST span scores were higher for the
      focused RST than for the nonfocused RST, and intrusion errors were found to
      increase for the nonfocused RST. In Experiment 2, the effect of focus was
      compared between high-span and low-span subjects. An effect of sentence length
      was also investigated. The result showed that low-span subjects were more
      affected than were high-span subjects by whether the word to be remembered was
      the focus word. The effect of sentence length was not confirmed. These findings
      suggest that the low-span subjects had deficits in their ability to establish
      and/or inhibit mental focus when faced with conflict situations in reading.

PMID- 12184558
TI  - Aging and time-sharing aspects of executive control.
AB  - A particularly important aspect of executive functioning involves the ability to
      coordinate two simultaneous activities. The role of this aspect of executive
      functioning in adult-age differences in cognitive performance was examined in a
      study involving 150 adults between 20 and 91 years of age who performed the same
      visual-motor tracking task with three different primary tasks. The participants
      also performed several additional cognitive tasks that allowed examination of the
      relation of time-sharing efficiency to other types of cognitive functioning The
      results were consistent with the existence of a distinct time-sharing ability
      because the time-sharing costs in the three dual-task combinations were
      significantly correlated with one another but only weakly correlated with other
      cognitive variables. Increased age was associated with reductions in time-sharing
      ability, and greater efficiency in performing two tasks at once was associated
      with better performance on tasks assessing spatial, reasoning, and memory
      abilities. Although this pattern is what one would expect if executive processes
      contribute to age differences in cognitive functioning, the effects were smaller
      than those associated with a perceptual speed construct.

PMID- 12184560
TI  - Concurrent activation of high- and low-level production processes in written
      composition.
AB  - Writing a text requires the coordination of multiple high-level composition
      processes in working memory, including planning, language generation, and
      reviewing, in addition to low-level motor transcription. Here, interference in
      reaction time (RT) for detecting auditory probes was used to measure the
      attentional demands of (1) copying in longhand a prepared text (transcription),
      (2) composing a text and pausing handwriting for longer than 250 msec
      (composition), and (3) composing and currently handwriting (transcription +
      composition). Greater interference in the transcription + composition condition
      than in the transcription condition implies that high-level processes are
      activated concurrently with motor execution, resulting in higher attentional
      demands. This difference was observed for adults who wrote in standard cursive,
      but not for children and not for adults who used an unpracticed uppercase script.
      Greater interference in the composition condition than in the transcription
      condition implies that high-level processes demand more attention than do motor
      processes. This difference was observed only when adults wrote with a practiced
      script. With motor execution being relatively automatic, adults were able to
      attend fully to the high-level processes required in mature, effective
      composition. One reason that children fail to engage in such high-level processes
      is that motor processes deplete available attention.

PMID- 12184559
TI  - Resolution of lexical ambiguity by emotional tone of voice.
AB  - In the present study, the effects of emotional tone of voice on the perception of
      word meaning were investigated. In two experiments, listeners were presented with
      emotional homophones that had one affective meaning (happy or sad) and one
      neutral meaning. In both experiments, the listeners were asked to transcribe the
      emotional homophones presented in three different affective tones--happy,
      neutral, and sad. In the first experiment, trials were blocked by tone of voice,
      and in the second experiment, tone of voice varied from trial to trial. The
      results showed that the listeners provided more affective than neutral
      transcriptions when the tone of voice was congruent with the emotional meaning of
      the homophone. These findings suggest that emotional tone of voice affects the
      processing of lexically ambiguous words by biasing the selection of word meaning.

PMID- 12184561
TI  - The spacing effect in the free recall of homogeneous lists: present and accounted
      for.
AB  - Memory performance nearly always improves as a function of the spacing between
      repetitions. However, previous studies indicated that college students exhibited
      no spacing effect in the free recall of lists composed exclusively of words
      sampled from a single semantic category. We explored this puzzling phenomenon in
      two experiments. We found that the spacing effect in free recall can occur with
      homogeneous lists. Most interestingly, the effect seems to depend on the number
      of items (lag) separating spaced repetitions. Short lags between spaced
      repetitions yield a spacing effect, whereas longer lags do not.

PMID- 12184562
TI  - Feature frequency effects in recognition memory.
AB  - Rare words are usually better recognized than common words, a finding in
      recognition memory known as the word-frequency effect. Some theories predict the
      word-frequency effect because they assume that rare words consist of more
      distinctive features than do common words (e.g., Shiffrin & Steyvers's, 1997, REM
      theory). In this study, recognition memory was tested for words that vary in the
      commonness of their orthographic features, and we found that recognition was best
      for words made up of primarily rare letters. In addition, a mirror effect was
      observed: Words with rare letters had a higher hit rate and a lower false-alarm
      rate than did words with common letters. We also found that normative word
      frequency affects recognition independently of letter frequency. Therefore, the
      distinctiveness of a word's orthographic features is one, but not the only,
      factor necessary to explain the word-frequency effect.

PMID- 12184563
TI  - Stroop effects in bilingual translation.
AB  - In two experiments, bilinguals proficient in English and Spanish translated words
      from one language to the other. In each experiment, following the target word to
      be translated, distractor words were presented after a short (200-msec) or long
      (500-msec) stimulus onset asynchrony. In Experiment 1, the distractor words
      appeared in the language of production and were related to the meaning or form of
      the spoken translation. The results replicated past studies in demonstrating that
      semantically related distractor words produced Stroop-type interference, whereas
      form-related distractor words produced facilitation. In Experiment 2, the
      distractors appeared in the language of input and were related to the meaning or
      form of the target word itself. In contrast to the results of Experiment 1, there
      were only marginal effects of the distractors on translation performance. These
      results suggest that language cues related to the nature of the input in
      translation may serve to reduce competition among lexical competitors during
      lexicalization. The contrast between these results and those in bilingual picture
      word interference studies provides important constraints for models of language
      production and for claims about the locus of language selection.

PMID- 12184564
TI  - Semantic aspects of morphological processing: transparency effects in Serbian.
AB  - We examined the contribution of semantics to morphological facilitation in the
      visual lexical decision task at two stimulus onset asynchronies (SOAs) with
      Serbian materials. Primes appeared in Roman or Cyrillic characters. Targets
      always were printed in Roman. When primes were presented at an SOA of 250 msec,
      decision latencies to verbal targets (e.g., VOLIM) showed greatest facilitation
      after inflectionally (e.g., VOLE) related primes, significantly less after
      semantically transparent derived primes (e.g., ZAVOLE), and less again after
      semantically opaque derived primes (e.g., PREVOLE). Latencies after semantically
      transparent and opaque derived target words did not differ at an SOA of 48 msec.
      Both were slower than after inflectionally related primes. Stated generally,
      effects of semantic transparency among derivationally related verb forms were
      evident at long SOAs, but not at short ones. Under alphabet-alternating
      conditions, magnitudes of facilitation were greater overall, but the pattern was
      similar. The outcome suggests that restricted processing time for the prime
      limits the contribution of semantics to morphological processing and calls into
      question accounts that posit a task-invariant semantic criterion for
      morphological decomposition within the lexicon.

PMID- 12184565
TI  - Priming relations in ambiguous noun-noun combinations.
AB  - We conducted two experiments to examine whether the interpretation of an
      ambiguous noun phrase is influenced by exposure to a similar combination. In
      Experiment 1, we found that it was easier to verify a definition for a
      combination (e.g., adolescent doctor, a doctor for adolescents) when the prime
      used the same relation as the target (e.g., adolescent magazine, a magazine for
      adolescents; animal doctor, a doctor for animals) than when the prime used a
      different relation (e.g., country doctor; adolescent experience). In Experiment
      2, we found that the interpretation generated for an ambiguous combination was
      affected by prior exposure to sentences containing a combination with the same
      modifier or head noun as the target combination. The data are inconsistent with
      key predictions of schema-based theories of conceptual combination. Although the
      results do not contradict key assumptions of relation-based theories,
      modifications to these theories are required to account for these data.

PMID- 12184566
TI  - Dissociations between categorization and similarity judgments as a result of
      learning feature distributions.
AB  - A dissociation between categorization and similarity was found by Rips (1989). In
      one experiment, Rips found that a stimulus halfway between a pizza and a quarter
      was categorized as a pizza but was rated as more similar to a quarter. Smith and
      Sloman (1994) discussed these results in terms of the role of necessary and
      characteristic features. In two experiments, participants had to learn to
      categorize novel artificial shapes composed of a nonsalient necessary feature
      combined with a salient characteristic feature. Participants categorized stimuli
      on the basis of a necessary feature, whereas their similarity judgments relied on
      characteristic features. The role of deep (essential) features in dissociations
      is considered. Results are discussed in terms of the differences between
      requirements of categorization and similarity judgments.

PMID- 12184567
TI  - Trust in leadership: meta-analytic findings and implications for research and
      practice.
AB  - In this study, the authors examined the findings and implications of the research
      on trust in leadership that has been conducted during the past 4 decades. First,
      the study provides estimates of the primary relationships between trust in
      leadership and key outcomes, antecedents, and correlates (k = 106). Second, the
      study explores how specifying the construct with alternative leadership referents
      (direct leaders vs. organizational leadership) and definitions (types of trust)
      results in systematically different relationships between trust in leadership and
      outcomes and antecedents. Direct leaders (e.g., supervisors) appear to be a
      particularly important referent of trust. Last, a theoretical framework is
      offered to provide parsimony to the expansive literature and to clarify the
      different perspectives on the construct of trust in leadership and its operation.

PMID- 12184568
TI  - The impact of outcome orientation and justice concerns on tax compliance: the
      role of taxpayers' identity.
AB  - Previous research has yielded inconsistent evidence for the impact of justice
      perceptions on tax compliance. This article suggests a more differentiated view
      on the basis of 2 congenial theories of procedural and distributive justice. The
      group-value model and a categorization approach argue that taxpayers are more
      concerned about justice and less about personal outcomes when they identify
      strongly with the inclusive category within which procedures and distributions
      apply. Regression analyses of survey data from 2,040 Australian citizens showed
      that 2 forms of tax compliance (pay-income reporting and tax minimization) were
      determined by self-interest variables. For 2 other forms (nonpay income and
      deductions), inclusive identification had an additional effect and moderated the
      effects of self-interest and justice variables as predicted.

PMID- 12184569
TI  - Is job search related to employment quality? It all depends on the fit.
AB  - In this longitudinal study on job search, fit perceptions, and employment
      quality, 113 graduates completed surveys prior to organizational entry and 4
      months after entry. Job search behavior and career planning were positively
      related to pre-entry person-job (P-J) and person-organization (P-O) fit
      perceptions, and pre-entry P-J fit perceptions mediated the relationship between
      career planning and postentry P-J fit perceptions. P-J and P-O fit perceptions
      were positively related to job and organizational attitudes, and pre-entry P-J
      fit perceptions mediated the relationship between career planning and job
      attitudes. Further, the relationships between pre-entry fit perceptions and
      employment quality were mediated by postentry fit perceptions. These results
      indicate that P-J and P-O fit perceptions play an important role in linking job
      search to employment quality.

PMID- 12184571
TI  - Investigating differential prediction by gender in employment-oriented
      personality measures.
AB  - Gender-based differential prediction of job performance in employment-oriented
      personality measures has been left virtually unexamined. The use of 3 personality
      composites from the U.S. Army's instrument to predict 5 dimensions of job
      performance across 9 military jobs was investigated. Differential prediction,
      occurring in one third of the cases, was predominantly in the form of
      overprediction of female performances (i.e., higher male intercepts); slope
      differences were not found at above-chance levels. Female performance on the
      Effort and Leadership dimension was overpredicted in 90% of all predictor
      criterion-job combinations, suggesting the measurement of this performance
      dimension as the source of the differential prediction rather than bias in the
      personality measures. Findings of overprediction of female performance parallel
      those of research investigating differential prediction by race in the ability
      domain.

PMID- 12184570
TI  - An examination of crossover and spillover effects of spousal and expatriate cross
      cultural adjustment on expatriate outcomes.
AB  - Integrating work-family and cross-cultural adjustment literatures, the
      researchers proposed and tested a spillover and crossover model of expatriates'
      cross-cultural adjustment with reciprocal relationships. Spillover effects refer
      to the influence that expatriate attitudes in a particular domain (e.g., work)
      have on attitudes in other domains (e.g., nonwork), whereas crossover effects
      refer to the influence of expatriate attitudes on the spouse's attitudes (and
      vice versa). Data collected from Japanese expatriates, their spouses, and their
      superiors strongly supported both spillover and crossover effects between
      expatriate and spousal cross-cultural adjustment. In addition, expatriates' cross
      cultural adjustment was found to be related to satisfaction, which, in turn, was
      found to be negatively related to expatriates' intention to return to their
      homeland early.

PMID- 12184572
TI  - Trying to understand the different pieces of the construct validity puzzle of
      assessment centers: an examination of assessor and assessee effects.
AB  - This study examined the effects of assessor-related factors (i.e., type of
      assessor) and assessee-related factors (i.e., type of assessee profile) on the
      construct validity of assessment center ratings. In particular, 3 types of
      assessors (26 industrial/organizational [I/O] psychologists, 20 managers, and 27
      students), rated assessee performances that varied according to cross-exercise
      consistency (i.e., relatively inconsistent vs. relatively consistent) and
      dimension differentiation (relatively undifferentiated vs. relatively
      differentiated). Construct validity evidence was established for only one
      assessee profile and only in the I/O psychologist and managerial samples. More
      generally, these results indicate that 3 factors (poor design, assessor
      unreliability, and especially cross-situational inconsistent assessee
      performances) may explain why construct validity evidence is often not
      established in operational assessment centers.

PMID- 12184573
TI  - Understanding when bad moods foster creativity and good ones don't: the role of
      context and clarity of feelings.
AB  - Using a mood-as-input model, the authors identified conditions under which
      negative moods are positively related, and positive moods are negatively related,
      to creative performance. Among a sample of workers in an organizational unit
      charged with developing creative designs and manufacturing techniques, the
      authors hypothesized and found that negative moods were positively related to
      creative performance when perceived recognition and rewards for creative
      performance and clarity of feelings (a metamood process) were high. The authors
      also hypothesized and found that positive moods were negatively related to
      creative performance when perceived recognition and rewards for creativity and
      clarity of feelings were high.

PMID- 12184574
TI  - Perceived organizational support: a review of the literature.
AB  - The authors reviewed more than 70 studies concerning employees' general belief
      that their work organization values their contribution and cares about their well
      being (perceived organizational support; POS). A meta-analysis indicated that 3
      major categories of beneficial treatment received by employees (i.e., fairness,
      supervisor support, and organizational rewards and favorable job conditions) were
      associated with POS. POS, in turn, was related to outcomes favorable to employees
      (e.g., job satisfaction, positive mood) and the organization (e.g., affective
      commitment, performance, and lessened withdrawal behavior). These relationships
      depended on processes assumed by organizational support theory: employees' belief
      that the organization's actions were discretionary, feeling of obligation to aid
      the organization, fulfillment of socioemotional needs, and performance-reward
      expectancies.

PMID- 12184575
TI  - Antecedents and outcomes of union loyalty: a constructive replication and an
      extension.
AB  - Primary data obtained from unionized employees in Singapore were used to examine
      P. A. Bamberger, A. N. Kluger, and R. Suchard's (1999) integrative model of the
      antecedents and outcomes of union commitment. Structural equation modeling
      results revealed support for their integrative model. Specifically, the results
      revealed the influence of job satisfaction on union loyalty to be indirect
      through organizational commitment. However, the union-related antecedents (union
      socialization and union instrumentality) were both directly and indirectly
      related to union loyalty through pro-union attitudes. In addition, union loyalty
      was related to the individually and organizationally directed union citizenship
      behavior dimensions. Limitations of the study and implications of the findings
      are discussed.

PMID- 12184576
TI  - A Web of applicant attraction: person-organization fit in the context of Web
      based recruitment.
AB  - Applicant attraction was examined in the context of Web-based recruitment. A
      person-organization (P-O) fit framework was adopted to examine how the provision
      of feedback to individuals regarding their potential P-O fit with an organization
      related to attraction. Objective and subjective P-O fit, agreement with fit
      feedback, and self-esteem also were examined in relation to attraction. Results
      of an experiment that manipulated fit feedback level after a self-assessment
      provided by a fictitious company Web site found that both feedback level and
      objective P-O fit were positively related to attraction. These relationships were
      fully mediated by subjective P-O fit. In addition, attraction was related to the
      interaction of objective fit, feedback, and agreement and objective fit,
      feedback, and self-esteem. Implications and future Web-based recruitment research
      directions are discussed.

PMID- 12184577
TI  - A new frame for frame-of-reference training: enhancing the construct validity of
      assessment centers.
AB  - The authors undertook a comprehensive examination of the construct validity of an
      assessment center in this study by (a) gathering many different types of evidence
      to evaluate the strength of the inference between predictor measures and
      constructs (e.g., reliability, accuracy, convergent and discriminant
      relationships), (b) introducing a theoretically relevant intervention (frame-of
      reference [FOR] training) aimed at improving construct validity, and (c)
      examining the effect of this intervention on criterion-related validity
      (something heretofore unexamined in the assessment center literature). Results
      from 58 assessees and 122 assessors suggested that FOR training was effective at
      improving the reliability, accuracy, convergent and discriminant validity, and
      criterion-related validity of assessment center ratings. Findings are discussed
      in terms of implications and future directions for both FOR training and
      assessment center practice.

PMID- 12184579
TI  - Personality and leadership: a qualitative and quantitative review.
AB  - This article provides a qualitative review of the trait perspective in leadership
      research, followed by a meta-analysis. The authors used the five-factor model as
      an organizing framework and meta-analyzed 222 correlations from 73 samples.
      Overall, the correlations with leadership were Neuroticism = -.24, Extraversion =
      .31, Openness to Experience = .24, Agreeableness = .08, and Conscientiousness =
      .28. Results indicated that the relations of Neuroticism, Extraversion, Openness
      to Experience, and Conscientiousness with leadership generalized in that more
      than 90% of the individual correlations were greater than 0. Extraversion was the
      most consistent correlate of leadership across study settings and leadership
      criteria (leader emergence and leadership effectiveness). Overall, the five
      factor model had a multiple correlation of .48 with leadership, indicating strong
      support for the leader trait perspective when traits are organized according to
      the five-factor model.

PMID- 12184578
TI  - The fit and implementation of sexual harassment law to workplace evaluations.
AB  - Three studies used videotaped harassment complaints to examine the impact of
      legal standards on the evaluation of social-sexual conduct at work. Study 1
      demonstrated that without legal instructions, college students' judgment
      strategies were highly variable. Study 2 compared 2 current legal standards, the
      "severity or pervasiveness test" and a proposed utilitarian alternative (i.e.,
      the rational woman approach). Undergraduate participants taking the perspective
      of the complainant were more sensitive to offensive conduct than were those
      adopting an objective perspective. Although the utilitarian altemative further
      increased sensitivity on some measures, it failed to produce a principled
      judgment strategy. Finally, Study 3 examined the kinds of errors that full-time
      workers make when applying the "severity or pervasiveness" test to examine more
      closely the sensitivity of the subjective approach.

PMID- 12184580
TI  - Commitment to legal claiming: influences of attributions, social guidance, and
      organizational tenure.
AB  - This study investigates antecedents of individuals' commitment to the legal
      claiming process. Individuals were surveyed as they entered a district office of
      the federal Equal Employment Opportunity Commission to file an employment
      discrimination claim. Respondents' attributions regarding who they blamed for
      their grievance, the social guidance received, their organizational tenure, and
      their commitment to legal claiming were assessed. Results showed that individuals
      who made strong external attributions had a higher commitment to legal claiming
      than did those who made weak external attributions. Social guidance and
      organizational tenure were significant moderators of the attribution-claiming
      relationship. Specifically, commitment to legal claiming was more strongly
      related to external attributions when social guidance was low and organizational
      tenure was high. Theoretical and practical implications are discussed.

PMID- 12184581
TI  - Interpersonal workplace stressors and well-being: a multi-wave study of employees
      with and without arthritis.
AB  - The within-person influence of interpersonal stressors on affective well-being
      and physical well-being was investigated for 109 women with and without
      arthritis. Participants were interviewed on a weekly basis for 12 consecutive
      weeks, and the prospective data were analyzed by using hierarchical linear
      modeling. Overall, interpersonal workplace stressors independently predicted both
      well-being outcomes. Interpersonal stressors outside the workplace were related
      to negative affect but not to arthritis symptoms. Compared with healthy controls,
      arthritis patients' ratings of negative affect were equally reactive to workplace
      stressors. Neuroticism did not moderate stressor reactivity for either dependent
      variable but did predict mean levels of negative affect. The data support the
      hypothesis that the psychosocial environment of the workplace contributes unique
      effects on well-being.

PMID- 12184582
TI  - Relationship of personality to performance motivation: a meta-analytic review.
AB  - This article provides a meta-analysis of the relationship between the five-factor
      model of personality and 3 central theories of performance motivation (goal
      setting, expectancy, and self-efficacy motivation). The quantitative review
      includes 150 correlations from 65 studies. Traits were organized according to the
      five-factor model of personality. Results indicated that Neuroticism (average
      validity = -.31) and Conscientiousness (average validity = .24) were the
      strongest and most consistent correlates of performance motivation across the 3
      theoretical perspectives. Results further indicated that the validity of 3 of the
      Big Five traits--Neuroticism, Extraversion, and Conscientiousness--generalized
      across studies. As a set, the Big Five traits had an average multiple correlation
      of .49 with the motivational criteria, suggesting that the Big Five traits are an
      important source of performance motivation.

PMID- 12184583
TI  - Liking and attributions of motives as mediators of the relationships between
      individuals' reputations, helpful behaviors, and raters' reward decisions.
AB  - Two studies investigated the mediating effects of liking and attributions of
      motives on the relationship between a ratee's reputation and helpful behaviors
      and raters' reward decisions. During managerial simulations, raters evaluated
      individuals after watching videotapes in which the individual's reputation and
      helpful behaviors were manipulated. Results indicated an interaction effect
      between reputation and helpful behaviors such that a helpful person with a good
      reputation received more rewards than did a helpful person with a bad reputation.
      In contrast, an unhelpful person with a good reputation did not receive better
      rewards than an unhelpful person with a bad reputation. Moreover, raters' liking
      of ratees and the motives raters attributed to ratees' helpful behaviors mediated
      the relationship between the manipulations and raters' reward decisions.

PMID- 12184584
TI  - Hepatocyte growth factor and its receptor c-met in rat and rabbit vocal folds.
AB  - Vocal fold fibrotic scar is characterized by fibrosis of the lamina propria and
      epithelium, and is difficult to treat. Hepatocyte growth factor (HGF) has
      antifibrotic activity and has received attention as a possible therapeutic
      alternative to treat fibrosis. In this study, in order to clarify whether HGF can
      be involved in vocal fold scarring, we examined the existence of HGF and its
      receptor, c-Met, in rat vocal folds, and then the activity of HGF in rabbit
      injured vocal folds, using immunohistochemistry and enzyme-linked immunosorbent
      assay. We found HGF and c-Met on epithelial cells and gland cells of the rat
      vocal folds. On the injured vocal folds of rabbits, little HGF was observed
      immediately after injury, but prominent activity occurred simultaneously with
      reepithelialization of the vocal fold mucosa on days 10 to 15. The activity of
      HGF was observed on fibroblasts in the lamina propria, as well as the epithelium.
      It is suggested that HGF in the vocal folds is produced by the fibroblasts and
      delivered to the epithelium. The implication of these findings is that HGF is
      involved in wound healing of the vocal fold, and may provide an alternative
      approach in preventing and treating vocal fold scarring.

PMID- 12184585
TI  - Type I thyroplasty for acute unilateral vocal fold paralysis following
      intrathoracic surgery.
AB  - Patients who undergo intrathoracic operative procedures for malignancy may
      require sacrifice of a recurrent laryngeal nerve. Postoperative vocal fold
      paralysis may lead to diminished cough with secretion retention, aspiration, and
      life-endangering pneumonia. This study retrospectively reviews our institution's
      experience of 23 patients who underwent type I thyroplasty within the 2-week
      (acute) period after thoracic surgery. Primary lung cancer (n = 16) was the most
      common disease. Upper lobectomy (n = 9) and pneumonectomy (n = 7) were the most
      frequent surgical procedures. Silicone medialization alone (n = 11) or with
      arytenoid adduction (n = 12) was performed. There were no significant
      postoperative complications. Improvements in hoarseness (86%), dyspnea (72%),
      dysphagia (50%), and aspiration (79%) were noted. Pulmonary status improved after
      vocal fold medialization, as reflected by decreased need for therapeutic
      bronchoscopy in the majority of patients in the postoperative period. Type I
      thyroplasty for vocal fold paralysis in the acute phase following thoracic
      surgery is well tolerated and is associated with improved patient outcome with no
      postoperative deaths in this high-risk patient population.

PMID- 12184586
TI  - Dysphagia and aspiration with unilateral vocal cord immobility: incidence,
      characterization, and response to surgical treatment.
AB  - To objectively determine the incidence of dysphagia associated with unilateral
      vocal cord immobility (UVCI) and to evaluate the potential for response to vocal
      cord medialization, we made videofluoroscopic swallowing (VFS) recordings of
      patients with newly diagnosed UVCI and prospectively analyzed them in a blinded
      fashion using the Penetration-Aspiration Scale (PAS) and pharyngeal transport
      function measures. A subset of patients underwent vocal cord medialization and
      were evaluated with a postoperative VFS study. Comparison was made between
      preoperative and postoperative VFS results to study the effects of vocal cord
      medialization in this setting. Eighty-seven VFS recordings were studied in 64
      adult patients with UVCI; 23 patients underwent VFS testing before and after
      vocal cord medialization. The UVCI was most commonly left-sided (53 cases) and
      most commonly resulted from thoracic or cardiac surgery (53.1%), followed by
      malignancy (15.6%). Overall, the median PAS score was 2.0 (25th-75th percentiles,
      1.0-5.0), with 20 patients (31.3%) and 15 patients (23.4%) exhibiting penetration
      or aspiration, respectively. No significant differences in swallowing function
      were noted between surgical and nonsurgical causes of paralysis (PAS scores of
      2.0 and 2.0, respectively; p = .901). The median PAS score improved from 4.0 to
      3.0 (p = .395, Wilcoxon paired samples test) in patients studied after undergoing
      a vocal cord medialization procedure (6 laryngoplasties and 17 vocal cord
      injections). Laryngoplasty was not more successful than vocal cord injection in
      resolving aspiration (p = .27). Radiographically significant penetration or
      aspiration occurs in approximately one third of patients with UVCI, independent
      of the cause of paralysis. Vocal cord medialization may not be as effective as
      thought for eliminating aspiration in these patients.

PMID- 12184587
TI  - Bilateral vocal fold paralysis and adhesion in anterior spinal artery syndrome.
AB  - The purpose of this report is to present a rare case of anterior spinal artery
      syndrome (ASAS) in which there proved to be a combined lesion of paralysis and
      adhesion. A 26-year-old woman with a history of ASAS complained of difficulty of
      tracheal decannulation. In 1988, she was intubated and underwent tracheotomy
      because of respiratory muscle weakness, and she was decannulated in 1990. In
      1998, she had cesarean delivery under general anesthesia, and postdelivery
      dyspnea necessitated tracheotomy again. On her first visit to us, endoscopic
      examination revealed bilateral vocal fold immobility at the midline without an
      apparent web. Direct laryngoscopy under general anesthesia revealed a posterior
      glottic adhesion and scarring, which were treated by excision of the scar and
      local steroid injection. The left vocal fold gradually regained mobility,
      permitting decannulation 3 months after treatment. This complicated vocal fold
      immobility was found to be due to adhesion and partial paralysis combined.

PMID- 12184588
TI  - Laryngeal-respiratory kinematics are impaired in aged rats.
AB  - Fatigue and weakness in the elderly are the functional consequences of underlying
      neuromuscular decline. However, little is known about the manifestations of aging
      in the larynx. This study evaluated the manner in which laryngeal senescence
      affects laryngeal-respiratory kinematics by videorecording laryngeal motion in
      both young and old rats. Recorded images were digitized, and glottal displacement
      and movement rate were measured. The results indicated that the amplitude of
      change in glottal angle was significantly diminished, and laryngeal movement
      durations were prolonged in the old animals. These findings may be due to
      functional constraints on the respiratory system, impaired laryngeal-respiratory
      interactions, or decrements in vocal fold tension with age. Because of the
      serious and pervasive nature of dysphagia and communicative impairments in the
      elderly, research that specifically examines the manifestations and causes of
      these impairments is of great importance.

PMID- 12184589
TI  - Idiopathic subglottic stenosis revisited.
AB  - Idiopathic subglottic stenosis (ISS) is a rare inflammatory process of unknown
      cause, usually limited to the subglottic region and the first 2 tracheal rings.
      We performed a retrospective analysis of our experience with a series of patients
      with this condition. The study involved retrospective review of the records of
      patients with ISS. A series of criteria that included patient clinical history,
      laboratory tests, flexible nasolaryngoscopic examination, and biopsies were used
      to establish a diagnosis. Symptoms, treatment, and outcome were examined. A total
      of 16 patients were identified; 14 were female (87.5%), and 2 were male. The mean
      follow-up time was 75.5 months. Fourteen patients required surgical treatment for
      respiratory compromise. Nine of these cases have been controlled effectively with
      endoscopic laser techniques. Endoscopic management failed in 5 patients, and 2
      patients underwent laryngotracheal resection and reconstruction. Mitomycin-C was
      used in 6 patients as an adjuvant to endoscopic laser surgery. Patients in whom
      endoscopic treatment failed were noted to have thicker (>1 cm) and more complex
      stenoses. The diagnosis of ISS is a diagnosis of exclusion. A complete workup of
      the patient must be performed to rule out other causes of stenosis. Endoscopic
      laser surgery is a valid initial approach for thinner, noncomplicated lesions.
      Patients with thicker, complex lesions in whom endoscopic treatment fails are
      best managed with laryngotracheal resection and reconstruction. However, adjuvant
      use of mitomycin-C may prove beneficial in the treatment of these patients.
      Estrogen may play a role in the pathogenesis of ISS by altering the wound healing
      response.

PMID- 12184590
TI  - Interference of nontypeable Haemophilus influenzae and Moraxella catarrhalis by
      Streptococcus oralis in adenoid organ culture: a possible strategy for the
      treatment of the otitis-prone child.
AB  - The role of viridans group streptococci (Streptococcus oralis) in the prevention
      of colonization with nontypeable Haemophilus influenzae and Moraxella catarrhalis
      was investigated in an adenoid organ culture system. The adenoids from 100
      patients who were undergoing adenoidectomy for either hypertrophy or recurrent
      otitis media were used. Streptococcus oralis Parker uniformly inhibited
      colonization with nontypeable H. influenzae or M. catarrhalis over a 24-hour
      period of incubation in adenoid organ culture. Streptococcus oralis Booth, a
      noninhibitory strain, did not significantly reduce colonization with nontypeable
      H. influenzae and M. catarrhalis. The results indicate that some strains of S.
      oralis may inhibit colonization with potential pathogens in the nasopharynx. It
      is therefore possible that colonization with inhibitory strains of viridans
      streptococci may be used in the nasopharynx as a relatively safe and inexpensive
      approach to prevention of recurrent otitis media in some children.

PMID- 12184591
TI  - Surgery of the nasal columella in external valve collapse.
AB  - The authors describe and discuss their experience with the collapse of the
      external nasal valve, focusing on the role that surgery of the columella plays in
      solving this problem. Thirty-seven cases were treated. In all but I there had
      been a previous septorhinoplasty. Seven patients had concomitant internal valve
      collapse. A modified alarplasty associated with columelloplasty was adopted in
      the cases with severe collapse. When the reduction of the nostril opening was
      mild to moderate, the surgical strategy varied depending on the width of the
      columella base: alarplasty in cases with a narrow to normal columella, and
      columelloplasty in the presence of a wide columella base. The authors' philosophy
      tends to minimize intervention on the nasal valve areas. Their results
      demonstrate that when the collapse and its functional effect are not too severe,
      a good result can be achieved by working only on the columella, especially if its
      base is significantly wide.

PMID- 12184593
TI  - Washout of 133-xenon as an objective assessment of paranasal sinus ventilation in
      endoscopic sinus surgery.
AB  - Endoscopic sinus surgery (ESS) is today a common method for the treatment of
      chronic rhinosinusitis. Assessment of the results has been based mainly upon
      subjective evaluation, and only a few reports present objective measurements. In
      the present study, the 133-xenon washout technique was used for preoperative and
      postoperative evaluation of paranasal sinus ventilation in 12 patients selected
      for ESS. The postoperative half-times (T1/2) of 133-xenon washout were lower in
      the sinuses with abnormal preoperative half-times (T1/2), especially in the
      maxillary sinuses, where the postoperative T1/2 was 44 (22 to 150) minutes
      (median and quartiles, Q1-Q3) as compared with a preoperative T1/2 of 202 (94 to
      278) minutes. The postoperative evaluation included a questionnaire and a follow
      up visit with endoscopy and measurements of nasal nitric oxide. The results
      showed that patients who declared a marked reduction in symptoms exhibited
      significantly improved sinus ventilation. However, no direct correlation was
      found between improvement in ventilation and symptom improvement. Nine of the 12
      patients showed improvement on endoscopy, and these patients also exhibited
      improved sinus ventilation. The postoperative nasal nitric oxide levels were
      within the normal range in 11 of the 12 patients; the other patient showed
      pathological T1/2 values for all paranasal sinuses. The 133-xenon washout
      technique is thus a method that can be used for objective evaluation of the
      ventilation of the paranasal sinuses before and after ESS procedures. However,
      the technique cannot be used to evaluate sinuses with totally obstructed ostia or
      postoperative sinuses with very wide neoostia, as rapid washout may lead to no
      activity remaining at the time of measurement.

PMID- 12184592
TI  - Comparison of surgical outcomes in primary endoscopic dacryocystorhinostomy with
      and without silicone intubation.
AB  - The surgical outcome of endoscopic endonasal dacryocystorhinostomy was analyzed
      in 30 cases of postsaccal stenosis. Intubation with silicone tubing was used in
      14 cases (46.7%) and not used in 16 cases (53.3%). Surgical success was evaluated
      subjectively and objectively. The patients' complaints were improved in 85.7% of
      cases in the intubation group, and in 81.3% of the group in which no stent was
      used. Postoperative endoscopic examinations revealed that the rhinostomy opening
      was visible in 11 cases without intubation (68.8%) and 9 cases with intubation
      (64.3%). Six patients in the intubation group (42.9%) had granulation tissue at
      the rhinostomy site. Four patients (28.6%) had complaints regarding the
      intubation. Considering the similar surgical success rates, and the granulation
      formation, patient discomfort, and cost related to intubation, we recommend
      endoscopic dacryocystorhinostomy without intubation as the treatment of choice in
      cases of chronic epiphora due to postsaccal stenosis of the lacrimal canal.

PMID- 12184594
TI  - Contribution of speech rate to speech perception in multichannel cochlear implant
      users.
AB  - This study describes the effect of speech rate (fast, 11 syllables per second;
      medium, 9 syllables per second; slow, 6 syllables per second) on speech
      perception in 10 cochlear implant users. The speech perception performance was
      evaluated on the basis of the percentage score of syllables that were correctly
      recalled in sentences composed of 4 to 6 words. The percentage scores at the
      fast, medium, and slow speech rates were 15.7%, 39.0%, and 56.0%, respectively.
      The effect of speech rate slowing was significant (p < .0001). Variations in the
      effect of speech rate slowing were observed in the cochlear implant users. The
      improvement of speech perception by speech rate slowing was significantly (p <
      .005) related to the word test score and the score at the fast speech rate. The
      results reveal that the rate of speech is an important factor in improving the
      speech perception of cochlear implant users.

PMID- 12184595
TI  - Temporal bone morphometric study on the eustachian tube and its associated
      structures in patients with chromosomal aberrations.
AB  - This study characterized phenotypic anomalies of the eustachian tube (ET) and its
      associated structures in individuals with various chromosomal aberrations
      (trisomies 13, 18, 21, and 22 and inversion of chromosome 1). The morphological
      characteristics of the ET and its accessory structures from 10 temporal bone-ET
      specimens, obtained from 10 individuals with chromosomal aberrations who ranged
      from the 26th gestational week to 1 year in age, were compared with the same
      structures from 21 age-matched control subjects without anomalies. The subjects
      with chromosomal aberrations had a significantly smaller volume of the lateral
      lamina (LL) of the ET cartilage, a reduced attachment of the tensor veli palatini
      muscle (TVPM), and, in some cases, a reduced volume of the lumen of the
      cartilaginous ET. The volume of the medial lamina (ML) of the ET cartilage was
      normal at birth, but smaller in specimens more than 2 months of age; this finding
      suggests that the prenatal development was normal, but that the postnatal growth
      was retarded. The subjects with chromosomal aberrations also displayed a smaller
      ratio of the volume of the LL to that of the ML (LL/ML ratio). Our results
      suggest that individuals with various chromosomal aberrations have rather similar
      anomalies of the ET and its associated structures. We speculate that these
      anomalies might be closely related to ET dysfunction in these patients.

PMID- 12184596
TI  - Evaluation of vertigo by auditory brain stem response.
AB  - The authors examined the hypothesis that abnormal patterns of the auditory brain
      stem response (ABR) could supplement the neuro-otological evaluation and assist
      in localizing the site of vestibulocerebellar dysfunction. This project is based
      upon the fact that the sources of waves I through V have been regionally
      identified. Absent or delayed patterns can be referenced to the normal data, and
      the site of a lesion generating vertigo can be established. We found absence of
      waves or prolonged interpeak latencies in 25% of the vertiginous subjects with
      normal hearing and magnetic resonance images of the brain. We conclude that in
      selected cases, lesions affecting the vestibular system can influence the ABR,
      and the electrophysiological tests of audition may suggest regionalization of the
      dysfunction in the hindbrain and midbrain.

PMID- 12184597
TI  - Vascular permeability to fluorescent substance in human cranial nerves.
AB  - It has recently been reported that in the facial canal, the facial nerve shows
      enhancement on gadolinium-enhanced magnetic resonance imaging in patients with
      clinically normal facial nerves. However, the mechanism of this enhancement has
      not yet been sufficiently clarified. The present study investigated the
      permeability of blood vessels in human cranial nerves that were obtained from
      surgically treated patients. The patients received an intravenous injection of
      sodium fluorescein 45 minutes before nerve resection. For histologic observation,
      the nerves were removed and frozen at -70 degrees C, and the sections were then
      cut at 4-microm thickness with a freezing microtome. The localization of the
      tracers was examined with a fluorescence microscope. Fluorescence was observed in
      the external nerve sheath and slightly in the endoneurium of these nerves, but
      was not observed within nerve fibers. These findings indicate that the vascular
      barrier in human peripheral nerves is incomplete.

PMID- 12184598
TI  - Acoustic analysis of upper airway obstruction in the excised human larynx.
AB  - Upper airway obstruction is an emergency that requires quick and decisive
      intervention. Stridor is the sound created by airflow through a partially
      obstructed airway, and has been described to vary with the site and degree of
      obstruction. This study sought to determine the sound characteristics of stridor
      in the excised human larynx. Five fresh cadaver human larynges were harvested and
      subjected to obstructions at supraglottic, glottic, and subglottic subsites.
      Subglottic pressure, airflow, and audio signal were recorded. Data were analyzed
      on the basis of laryngeal obstruction subsite and the degree of laryngeal
      resistance. Visual inspection demonstrated certain trends in peak spectral energy
      depending on the site and, more significantly, the amount of obstruction.
      Statistical analysis of spectral waveforms showed better correlation with the
      amount of obstruction than with the site of obstruction. In summary, the
      frequency distribution of stridor produced in an excised human larynx was
      influenced by the amount of laryngeal resistance, but not by the site of airway
      obstruction.

PMID- 12184599
TI  - Cisplatin-induced ototoxicity and pharmacokinetics: preliminary findings in a dog
      model.
AB  - The early effects of a clinical dose of cisplatin (100 mg/m2) on distortion
      product otoacoustic emissions (DPOAE) thresholds and the relationship between
      DPOAE threshold shifts and changes in plasma concentrations of filterable and
      total platinum (Pt) following infusion of cisplatin in a dog model were
      investigated. The DPOAE thresholds (based on input-output function) were measured
      2 days before a single high dose of cisplatin administration, and compared with
      measurements recorded 2 and 4 days after infusion. The results revealed DPOAE
      thresholds to be elevated by 4 days after the administration of cisplatin.
      However, this elevation could not be correlated with plasma concentrations of
      filterable and total Pt, which showed little variation over the 48-hour
      postinfusion period between animals. The present study demonstrated that DPOAE
      thresholds have the potential to be used as an indicator of cisplatin-induced
      ototoxicity, and cisplatin-induced ototoxicity could not be explained by plasma
      Pt kinetics in individual animals.

PMID- 12184600
TI  - Multiple and synchronous peripheral giant cell granulomas of the gums.
AB  - The presence of multiple giant cell lesions in the maxillofacial region is
      suggestive of hyperparathyroidism or neurofibromatosis. A case of synchronous,
      multiple peripheral giant cell granulomas is reported, bilaterally affecting the
      mandibular gums and also the upper right maxillary gingival mucosa, without
      concomitant systemic disease. Only 2 cases of central giant cell granulomas, and
      no cases of peripheral giant cell granulomas exhibiting similar characteristics,
      have been reported in the literature to date.

PMID- 12184601
TI  - Granular cell tumor of the pituitary fossa.
AB  - Although granular cell tumors are relatively common in the head and neck,
      symptomatic granular cell tumors of the neurohypophysis are extremely rare.
      Ophthalmologic symptoms are most common, followed by endocrinologic
      manifestations. We report a case of a granular cell tumor of the pituitary fossa
      that was surgically treated. The clinical manifestations, radiographic
      appearance, and surgical management of granular cell tumors of the pituitary
      fossa are reviewed, as well as the unique histopathology and electron microscopy
      of this uncommon neoplasm.

PMID- 12184602
TI  - Progression of late-stage chronic maxillary atelectasis.

PMID- 12184603
TI  - The core concepts of the 'four principles' of bioethics as found in Islamic
      tradition.
AB  - Ethics can be described as a sub-branch of applied philosophy that seeks 'what is
      the right and the wrong, the good and the bad set of behaviours in a given
      circumstance'. Bioethics, however, is a quasi-social science that offers
      solutions to the moral conflicts arising in medical and biological science
      practice. There have been different ethical approaches to the issues in the
      history of philosophy. Two American philosophers, Beauchamp and Childress,
      formulated some ethical principles namely 'respect to autonomy', 'justice',
      'beneficence' and 'non-maleficence'. These 'Four Principles' which have almost
      always existed and govern the ethical behaviour of human societies, were
      presented by the authors as universal and applicable to any culture and society.
      These 'Four Principles' have been one of the most widely discussed issues in
      Biomedical Ethics with arguments for and against them. The authors' claim has
      been tested by research conducted in different cultures and societies. In this
      study we aim to explore the roots of the 'Four Principles' in Islamic tradition
      and culture, and show that this particular set of principles are not something
      new but only one of the latest formulations of age-old common sense principles.
      It is therefore concluded that these principles are already being applied in
      Islamic traditional and cultural societies.

PMID- 12184604
TI  - Islamic ethics of saving life: a comparative perspective.
AB  - Addressing specific modes of reasoning common to legal and theological
      discussions, this paper seeks to understand how the modern debate on euthanasia
      fits into a broader Islamic worldview. After an overview of contrasting religious
      and secular ethical theories, the paper demonstrates that Islamic theological
      views, and also traditions on martyrdom and suicide, continue to inform Muslim
      authorities today. Also included are specific suggestions on the incorporation of
      Islamic ideas of death into the modern hospital environment.

PMID- 12184605
TI  - Bioethical conflicts between Muslim patients and German physicians and the
      principles of biomedical ethics.
AB  - In the age of globalisation, more and more people who are members of different
      religions and cultures live in the same society. This situation tends to create
      many conflicts in different areas of life and not least in the health care
      system, a fact which raises a number of bioethical issues. The cultural and
      religious differences between patient and physician can be a cause of bioethical
      conflicts and therefore represent a challenge for biomedical ethics. The
      confrontation between Turkish Muslin patients and the German health care system
      is a convenient example of this situation. The Muslim Turks came to Germany 40
      years ago as industrial workers. Their value system had been shaped by
      traditional and Islamic parameters in Turkey. With this value system, they now
      found themselves in the German modern health care system. In many fields of
      modern medicine there are areas of potential conflict of values, where a Muslin
      patient will argue differently from a secular or Christian person. In an ethical
      conflict between two individuals who are members of different cultures, it is
      necessary to make sure that the ethical concept which is to be used for resolving
      the problem is relevant. In this particular case, both the Islamic legal
      responses (fatwa) and the classical theories of biomedical ethics are often
      insufficient. This paper tries to give a brief outline of these bioethical
      conflicts and discuss these conflicts with regard to the principle of respect for
      autonomy in the concept of "principilism," as introduced by T.L. Beauchamp and
      J.F. Childress. The central question is whether this bioethical concept is able
      to analyse and to help solve the kinds of ethical conflicts which involve
      transcultural dimensions. This question is discussed with some consideration of
      the ongoing debate about universalism versus relativism in biomedical ethics.

PMID- 12184606
TI  - A descriptive analysis of South African and Islamic abortion legislation and
      local Muslim community responses.
AB  - The issue of abortion has been the subject of much debate in the recent past in
      South Africa. Prior to 1996 abortion legislation was punitive and therefore one
      with which conservative Muslims could identify. Since 1996 the law has been
      liberalized and replaced by a new Act. The final Constitution (1996) took a
      neutral stance regarding abortion. The enactment of the Choice on Termination on
      Pregnancy Act (1996) finally ensured this right. The Act, a critical milestone
      for gender equality, secured all South African women (including minors) the right
      to make decisions about reproduction and according to their individual beliefs.
      Muslim organizations participated in this abortion debate making formal but
      opposing submissions to Parliament. These opposing views of Muslims came as no
      surprise and reflect the different norms of Islamic law which varies between
      countries and was indicative of the interpretative duality evident in most
      matters of Islamic law.

PMID- 12184607
TI  - Without discrimination for religion, race, or gender.
AB  - The transplantation of organs, which at first sight appears to be just a
      technical medical procedure, is, first and foremost a sociocultural action that
      gives expression to existential perceptions. In Israeli society, as in most
      western societies the donation of the body or parts of it, is interpreted as
      possible at a societal level, and not as a gift from one individual to another.
      The medical achievement inherent in organ transplantation brings forward the
      relationship between the body, death and society. The moment the body ceases to
      function biologically, its position within the social entity is examined. The
      donation of organs evinces the acceptance of the idea that the personal body
      belongs to the society which sanctions the transition of the private body into
      organs that become national assets. This research is a first attempt to study the
      motives of people from Muslim society, who donated organs of their dear ones. The
      ability of these people to enter into a system of exchange flows from a tacit
      assumption by all of them that the action is approved by their social group. This
      paper presents the concepts of death and of the body that enable donation in
      general and the donation of the Muslim population in particular.

PMID- 12184608
TI  - Diagnosis through rosary and sand: Islamic elements in the healing custom of the
      Yoruba (Nigeria).
AB  - The inhabitants of south western Nigeria are known as the Yoruba. Their earliest
      contact with Islam goes back to the 14th century, but it was only in the 19th
      century that the faith got firmly established, as Islamic mores and intellectual
      culture which included medical tradition - became well entrenched. Before the
      advent of Islam, diagnosis of ailments, witchcraft attacks etc., was carried out
      through a traditional procedure which involved the use of palm kernels, cowries,
      the latter similar to "bone throwing" among the Zulu of South Africa. This
      traditional system has since lost position to divination with rosary (subha) and
      sand (khatt al-raml), particularly among Muslims. This development
      notwithstanding, elements of the indigenous medical tradition medical tradition
      have been incorporated into the Islamic tradition. Inam Ahmad al-Buni (d.622.H)
      remains a point of reference among Yorouba Muslim healers and standard works on
      divination with sand, for example, Ahmad al-Afandi's (fl.1290 A.H.) ilm al-raml
      and al-Adhami's Mizan al-adl fi masqasis ahkam al-raml (1322.A.H.) continue to be
      popular. Nevertheless, the native Muslim diviners have developed their own
      literature for this and for divination with rosary, which betrays the level of
      their linguistic competence as well as the degree of acculturation and
      hybridization of indigenous and Islamic elements in a healing custom. This paper
      will examine how traditional elements had been grafted on Islamic divination, and
      how the practitioners continue to resolve the inherent contradictions between the
      two phenomena in their dual role as votaries of the Islamic faith and social
      workers in a medical tradition with a strong religious underpinning.

PMID- 12184609
TI  - Medical and professional ethics in sixteenth-century Istanbul: towards an
      understanding of the relationships between the Ottoman State and the medical
      guilds.
AB  - This paper contributes to the understanding of Ottoman medical guilds, their
      relationship with the government, and the role played by medical ethics in this
      framework. Decrees by the sultans (sing. ferman), issued in the Ottoman Imperial
      Council (Divan) in Istanbul during the sixteenth century, concern themselves also
      with medical and ethical issues. The sheer number of these decrees may give the
      erroneous impression that the quality of medicine in the Ottoman Empire was low.
      This paper argues, however, that many of the complaints brought before the
      Ottoman authorities were instigated by medical guilds' members against their
      colleagues and competitors, not by aggravated patients demanding compensation
      from negligent healers. The discourse of medical ethics was raised in these cases
      not for its own sake, rather it embodied efforts by medical guild members to
      defend their economic interests and their intellectual and social status in the
      brutal competition in the medical realm.

PMID- 12184610
TI  - The professional ethics of medieval pharmacists in the Islamic world.
AB  - Most work on Islamic medical ethics has been in relation to the physician, yet
      physicians are only one category of many health-related professionals. In view of
      its role as mediator between the layman and medication, pharmacy is of perhaps
      equal importance. In medieval Islam, there seems to have been a clear
      differentiation between the physician and the pharmacist. However, most of our
      sources reflect the physician's point of view. A text which uniquely reflects
      that of the pharmacist is the thirteenth-century Minhaj al-dukkan by al-Kuhin al
      'Attar of Cairo. A comparison between the ethical contents of this book, and of
      similar works aimed at physicians, can indicate what the differences and
      similarities were between the "good physician" and the "good pharmacist."
      Interestingly, the language used to define the "go od" professional is
      religiously neutral--there is nothing to evince a particular identity, beyond a
      general monotheism, on the part of the writers.

PMID- 12184611
TI  - Islamic conceptions of the evil eye.

PMID- 12184612
TI  - Revealing the secrets of the body: medical tests as legal evidence in personal
      status disputes in modern Egypt.
AB  - The study seeks to answer the following question: In the field of personal
      status, what kinds of medical tests have been considered reliable and acceptable
      by Egyptian courts of law, what kinds have been less accepted, and why? The main
      finding is that, on the one hand, the judges (qadis) have welcomed tests that
      seek to determine age or to discover physical diseases and/or mental disorders.
      On the other hand, they have been reluctant to introduce tests to determine
      virginity and pregnancy tests, and even more so to introduce paternity tests that
      might bring into light manifestations of moral laxity within Egyptian society and
      jeopardize the future of illegitimate children. In conclusion, the main
      resistance to the reliance on modern medical evidence has not been the lack of
      modern knowledge and technologies or opposition to this, but rather traditional
      moral and social perceptions.

PMID- 12184613
TI  - AIDS in contemporary Islamic ethical literature.
AB  - AIDS has been mentioned in Islamic ethical literature since about 1985 as an
      illness pertaining to European and American homosexuals. Only since about 1990
      has the presence of HIV/AIDS in Islamic countries cast light on the fact that the
      actual sexual behaviour of the population does not always conform to religious
      norms. The increase in the numbers of people with HIV has compelled religious
      leaders to take a stand on sexual practices they consider "deviant", from
      prostitution to homosexuality and extramarital sex. The aim of this paper is to
      analyse the attitude of Muslim religious authorities towards individual sexual
      behaviour and AIDS. It is based mainly on contemporary legal responses that
      largely provide the necessary information on most of Islamic medical ethics.
      According to Muslim scholars, AIDS is a warning from God not to indulge in
      illicit conduct. As a remedy against the spread of AIDS, they encourage
      compliance with traditional family values and the enhancement of faith and
      devotion and strongly oppose sex education. They oppose promotion of condoms or
      any form of safe sex outside of marriage, which they perceive as promoting
      promiscuity and defiance of divine law. All the above-mentioned arguments are not
      exhaustive of the Islamic attitude towards AIDS. Some religious groups disagree
      with such a conservative way of conceiving the fight against AIDS as being
      antithetical to both men's and women's well-being. They support an alternative
      view of reproductive health and human rights within the Islamic framework and
      stress the great tolerance of Islam and why it must include people with HIV and
      AIDS.

PMID- 12184614
TI  - Ethical considerations in Syria regarding reproduction techniques.
AB  - Ethical Islamic considerations concerning current medical infertility treatment
      are outlined, that allow application of all techniques as far as they are
      compatible with legal marriage: Homogenic insemination is allowed. Heterogenic
      insemination is not, although it bears slightly better outcome, because of the
      imperative Islamic rule not to mingle genealogical lines. Neither is surrogate
      motherhood because of the legal position of the mother in Islamic shari'a and
      consequent inheritance rights on the one hand and sociological significance of
      motherhood on the other. The question arises, which is the mother, the biological
      or the social. In all cases, special attention should be paid to the
      professionals involved in the procedures. The danger of embryonic sex selection
      following preimplantation diagnostics is hinted at, precautions should be taken.
      These ethical considerations are substantial in Arab countries, including Syria.

PMID- 12184616
TI  - Behavioural language.

PMID- 12184615
TI  - Islam and "female circumcision": the dispute over FGM in the Egyptian press,
      September 1994.
AB  - In September 1994, during the United Nations Population Conference in Cairo, CNN
      broadcast a report about the custom of clitoridectomy in Egypt. The televised
      report included footage of such a ceremony performed on a ten-year-old Egyptian
      girl in Cairo a few days earlier. This broadcast revived the public polemics on
      clitoridectomy in Egypt. Secular newspapers such as al-Wafd and al-Ahali opposed
      this practice while religious circles used the al-Sha'b newspaper to justify it.
      The religious argument is based on Islamic tradition although the origin of the
      practice is admittedly pre-Islamic. This position maintains that the type of
      clitoridectomy performed involves minimal excision, but in practice it is much
      more radical. There are voices from within the lslamic camp, mainly those of
      women, that call for the abolition of this practice, basing this demand on the
      fact that this act is a minor rather than major principle of Islamic Law.
      Although the secular educated classes in Egypt tend to avoid this practice, they
      are a minority. The public argument continues in a low key while in reality
      thousands of young girls daily undergo this traumatic experience which maims them
      in body and in soul. Unless there is a sustained public outcry against it, this
      mutilation is destined to remain part of the Egyptian reality for a long time.
      This paper discusses the positions of the two sides to the dispute, concentrating
      mainly on the opinions of the Islamic faction which upholds the continuation of
      genital mutilation. These opinions are expressed by male Islamic elders while
      opposing arguments are presented by women who decry this practice.

PMID- 12184617
TI  - Study on the concentration effects in size exclusion chromatography VII. A
      quantitative verification for the model theory of concentration and molecular
      mass dependences of hydrodynamic volumes for polydisperse polymers.
AB  - A model theory of concentration effects for polydisperse polymers was proposed in
      1988. It is successful in relating the concentration of the injected solution to
      the effective hydrodynamic volumes of peak, the retention volumes of peak and the
      polydispersity index (Dc = (Vhcw)/(Vhcn) of hydro-dynamic volume distribution for
      polydisperse polymers at a given concentration. The dependence of the
      concentration of injected polymer solution on the effective hydrodynamic volumes,
      the retention volumes of peak and the polydispersity index of hydrodynamic volume
      distribution for narrow disperse and polydisperse polystyrene, poly(dodecyl
      methacrylate), poly(tridecyl methacrylate) and poly(methyl methacrylate) in
      tetrahydrofuran solvent were studied. The proposed theory was verified by these
      experimental data. Results show that the proposed theory can predict the
      concentration effects in GPC for polydisperse polymers quantitatively and can
      provide a theoretical foundation for the two methods of calibrating the universal
      calibration curves with polydisperse polymers and of determining the second
      virial coefficients (A2) of polymers. It is found that the determined values of
      A2 for narrow disperse and polydisperse polymers by the proposed method are in
      agreement with those obtained by the LALLS method, and the two universal
      calibration curves with narrow disperse and polydisperse polymers are in
      excellent agreement.

PMID- 12184618
TI  - Column selectivity in reversed-phase liquid chromatography I. A general
      quantitative relationship.
AB  - Retention factors k have been measured for 67 neutral, acidic and basic solutes
      of highly diverse molecular structure (size, shape, polarity, hydrogen bonding,
      pKa, etc.) on 10 different C18 columns (other conditions constant). These data
      have been combined with k values from a previous study (86 solutes, five
      different C8 and C18 columns) to develop a six-term equation for the correlation
      of retention as a function of solute and column. Values of k can be correlated
      with an accuracy of +/- 1-2% (1 standard deviation). This suggests that all
      significant contributions to column selectivity have been identified (and can be
      measured) for individual alkyl-silica columns which do not have an embedded polar
      group. That is, columns of the latter kind can be quantitatively characterized in
      terms of selectivity for use in the separation of any sample.

PMID- 12184619
TI  - Column selectivity in reversed-phase liquid chromatography II. Effect of a change
      in conditions.
AB  - The isocratic retention of 67 widely-different solutes in reversed-phase liquid
      chromatography (RP-LC) has been investigated as a function of temperature and
      mobile phase composition (% B) for three different C18 columns. Similar studies
      were also carried out in a gradient mode, where temperature, gradient time and
      solvent type were varied. These results show that changes in retention with these
      conditions are similar for each of these three columns. This suggests that
      relative column selectivity as defined by experiments for one set of experimental
      conditions will be approximately applicable for other conditions, with the
      exception of changes in mobile phase pH-which can affect values of the column
      parameter C (a measure of silanol ionization). Column selectivity as a function
      of pH was explored for several columns.

PMID- 12184620
TI  - Column selectivity in reversed-phase liquid chromatography III. The physico
      chemical basis of selectivity.
AB  - Reversed-phase liquid chromatography (RP-LC) retention data for 23 additional
      solutes have been acquired to further test and evaluate a general relationship
      from part I: log alpha = log (k/kref) = eta'H(i) + sigma'S(ii) beta'S(iii) +
      alpha'B(iv) +kappa'C(v) The physico-chemical origin of terms i-v above is
      examined here by comparing values of (a) the solute parameters of Eq. (1) (eta',
      sigma', etc.) vs. solute molecular structure, and (b) the column parameters (H,
      S, etc.) vs. column properties (ligand length and concentration, pore diameter,
      end-capping). We conclude that terms i-v correspond, respectively, to hydrophobic
      (i), steric (ii), hydrogen bonding (iii, iv) and ionic (v) interactions between
      solute and stationary phase. While steric interaction (term ii) is superficially
      similar to what previously has been defined as "shape selectivity", the role of
      the solute and column in determining steric selectivity (term ii) appears more
      complex than previously proposed for "shape selectivity". Similarly, what has
      previously been called hydrogen bonding between donor solutes and an acceptor
      group in the stationary phase (term iv) is very likely an oversimplification.

PMID- 12184621
TI  - Chromatographic alignment by warping and dynamic programming as a pre-processing
      tool for PARAFAC modelling of liquid chromatography-mass spectrometry data.
AB  - Solutes analysed with LC-MS are characterised by their retention times and mass
      spectra, and quantified by the intensities measured. This highly selective
      information can be extracted by multiway modelling. However, for full use and
      interpretability it is necessary that the assumptions made for the model are
      valid. For PARAFAC modelling, the assumption is a trilinear data structure. With
      LC-MS, several factors, e.g. non-linear detector response and ionisation
      suppression may introduce deviations from trilinearity. The single largest
      problem, however, is the retention time shifts not related to the true sample
      variations. In this paper, a time warping algorithm for alignment of LC-MS data
      in the chromatographic direction has been examined. Several refinements have been
      implemented and the features are demonstrated for both simulated and real data.
      With moderate time shifts present in the data, pre-processing with this algorithm
      yields approximately trilinear data for which reasonable models can be made.

PMID- 12184622
TI  - Liquid chromatographic-tandem mass spectrometric determination of nonylphenol
      polyethoxylates and nonylphenol carboxylic acids in surface water.
AB  - This paper presents a new LC-MS-MS method for the determination of the
      concentration of nonylphenol ethoxylates (NPEOs) and nonylphenol carboxylic acids
      (NPECs) in surface and drinking water using a reversed-phase column, which is
      fast and specific by nature. This method allows the simultaneous analysis of the
      two families of compounds in the same extract. Liquid-solid extraction of 100 ml
      of sample is performed on graphitized carbon black (GCB) cartridges. Reversed
      phase chromatography is performed on a C8 column with isocratic elution. The
      electrospray interface is used to monitor the [M+NH4]+ ion for NPEOs and the [M
      H]- ion for NPECs. Detection limits range from 0.01 to 0.05 microg/l for NP(1
      17)EOs and are 0.01 microg/l for NP(1-2)ECs. Mean recoveries range from 78 to
      107% with relative standard deviations ranging from 6 to 16%. Applicability of
      the method is demonstrated by results from a monthly sampling of river water at
      11 sampling points located downstream of suspected polluting industries in Quebec
      (Canada).

PMID- 12184623
TI  - Quantitative approach for the screening of cyclodextrins by nuclear magnetic
      resonance spectroscopy in support of chiral separations in liquid chromatography
      and capillary electrophoresis enantioseparation of norgestrel with alpha-, beta-
      and gamma-cyclodextrins.
AB  - A quantitative NMR approach is proposed for the screening of cyclodextrins with
      regard to their enantioselectivity as chiral mobile phase additives in column
      reversed-phase chromatography and capillary electrophoresis. Similarities and
      differences between the mechanism of enantiomeric peak-separation in NMR and HPLC
      and CE are interpreted. The affinity of d-norgestrel to bind to (alpha-, beta-,
      gammay-) cyclodextrins in aqueous solution was quantified and compared by
      determining the association constants from chemical shift data. The association
      constant of l-norgestrel was estimated from titration of the racemate.
      Differences between the apparent association constants of the enantiomerically
      pure drug and the racemate are discussed from the point of view of enantiomeric
      competition for the cyclodextrin. The apparent association constants and chiral
      selectivities determined by 'H NMR for dl-norgestrell/gamma-CD system at various
      water-methanol ratios are correlated with the corresponding chromatographic
      results found in the literature. The pitfalls of previously proposed screening
      methods based on comparison of chemical shift differences with separation
      parameters are discussed.

PMID- 12184624
TI  - Correlation of retention parameters of pesticides in normal- and reversed-phase
      systems and their utilization for the separation of a mixture of 14 triazines and
      urea herbicides by means of two-dimensional thin-layer chromatography.
AB  - The selectivities of TLC systems were compared by use of correlations between
      RF(II) and RF(I) (by analogy with two-dimensional TLC). The greatest spread of
      points, indicative of individual selectivity, was obtained for nonaqueous mobile
      phases on silica and aqueous mobile phases on octadecyl silica adsorbent wettable
      with water (RP-18 W). The correlation of RF values in normal- and reversed-phase
      systems was utilized in the practical separation of a mixture of 14 triazines and
      urea herbicides using two-dimensional thin-layer chromatography on a Multi-K CS5
      dual phase (3 cm strip of octadecyl silica parallel to silica layer). The plate
      was videoscanned showing the real picture of the plate.

PMID- 12184625
TI  - Evaluation of extended light path capillary and etched capillary for use in open
      tubular capillary electrochromatography.
AB  - Poor sensitivity and low phase ratio are the main drawbacks of open tubular
      capillary electrochromatography (OTCEC). The poor sensitivity results from the
      use of narrow bore size capillary, whereas the low phase ratio, which limits the
      separation capability, is caused by the limited surface area of conventional
      capillary. Two strategies may be useful to overcome these disadvantages. First,
      an extended light path (ELP) capillary, which has a bubble cell at the detection
      point, is used to improve the sensitivity. Secondly, an etched capillary of a
      1,000-fold increased surface area is used to enhance the phase ratio. In this
      work, use of an ELP capillary and an etched capillary in OTCEC was evaluated with
      a chiral stationary phase of avidin prepared with the physical adsorption method.
      With a 20 microm I.D. ELP capillary with a 150 microm bubble cell, the peak
      height was enhanced by 4-10-fold and the corrected peak area was increased by 12
      fold relative to a 20 microm I.D. conventional capillary. However, the peak
      efficiency and resolution decreased noticeably. The phase ratio on the etched
      capillary was slightly enhanced, by a factor of 1.64 relative to an unetched
      capillary. Consequently, the separation capability was slightly improved. The
      increase in the phase ratio was much lower than that expected from the increase
      in surface area, the reason for which is probably the reduced density of surface
      silanol group and the generation of nitrogen-containing groups due to the etching
      process.

PMID- 12184626
TI  - Comments on "Ion-exchange liquid chromatographic analysis of bisphosphonates by
      on-line post-column photochemical reaction and spectrophotometric detection" [J.
      Chromatogr. A 914 (2001) 105-110].

PMID- 12184627
TI  - Cell contact-dependent PMN HLA-DR and CD69 membrane expression induced by
      autologous mono-lymphocytes and cell lines.
AB  - Polymorphonuclear granulocytes (PMN) are commonly considered short-lived cells
      playing an efficient role in primary host defense via phagocytosis and release of
      cytotoxic compounds and inflammatory cytokines. Purified PMN do not express HLA
      DR and CD69 molecules on cell surface, but they can be induced to do so by co
      culture with peripheral blood derived mono-lymphocytes. De novo cell-surface
      expression of HLA-DR was also induced in PMN by co-culture with cell lines of
      lymphoid phenotype, but not with cell lines of myeloid phenotype. CD69 expression
      was not induced by co-culture with any of the cell lines used in the present
      study. In addition, we have observed induction of HLA-DR surface expression on
      PMN by culture in presence of culture supernatant of one of the cell lines of
      lymphoid origin, RPMI-8866. Quantitative analysis of HLA-DR and CD69 expression
      in stimulated PMN allowed us to divide PMN donors in two main groups, one with
      low expression and the other with high expression of the two molecules. HLA-DR
      surface expression was not altered by treatment with CHX and BFA, and RT-PCR
      analysis of total RNA from resting and stimulated PMN with RPMI-8866 supernatant
      did not detect the presence of any specific HLA-DR and CIITA transcript. Flow
      cytometry and fluorescence microscopy analysis of resting PMN revealed the
      presence of HLA-DR molecules localized in intracellular vesicular-tubular
      structures. These data show that a reservoir of HLA-DR molecules is stored in the
      cytoplasm of human resting PMN and can be released to reach cell surface by a
      mobilization mechanism induced by cell surface interactions with selected cell
      types and sometimes with molecules released in culture supernatants.

PMID- 12184628
TI  - Ferritin and desferrioxamine attenuate xanthine oxidase-dependent leak in
      isolated perfused rat lungs.
AB  - Iron, through its participation in reactions that generate reactive oxygen
      species, may contribute to the oxidative lung injury observed in patients with
      acute lung injury (ALI) and the acute respiratory distress syndrome (ARDS). A
      number of investigators have shown that the endogenous iron storage protein
      ferritin increases in the blood of patients with and at-risk for ALI and ARDS,
      but the significance of these increases are not known. In the present
      investigation, we measured lung tissue levels of thiobarbituric acid reactive
      substances (TBARS) and lung leak in isolated rat lungs perfused with xanthine
      oxidase (XO) and purine, an enzymatic system which generates reactive oxygen
      species. We found that adding ferritin (100 ng/mL) or desferrioxamine (DFO, 10
      mM), an iron chelator, to the vascular perfusate solution decreased oxidant
      induced leak in isolated rat lungs perfused with XO and purine. Addition of
      ferritin or DFO also decreased TBARS in isolated rat lungs perfused with XO and
      purine; neither ferritin nor DFO, however, decreased XO activity in vitro. Our
      results suggest that oxidative lung leak may be altered by the availability of
      reactive iron and that ferritin may contribute to protection against oxidative
      lung injury.

PMID- 12184629
TI  - Intrathecal clonidine decreases spinal nitric oxide release in a rat model of
      complete Freund's adjuvant induced inflammatory pain.
AB  - A long-lasting antihyperalgesic effect has been demonstrated for intrathecal (IT)
      clonidine, an alpha2-adrenergic agonist. In the present study, the mechanism and
      antihyperalgesic effects of IT clonidine were examined post-treatment in a rat
      model of Complete Freund's Adjuvant (CFA)-induced inflammatory hyperalgesia.
      Using a chronic model of spinal cord dialysis, we examined the effect of the
      adjuvant-induced inflammation on spinal release of nitric oxide (NO) and the
      development of chronic pain and assessed the antinociceptive effects and
      mechanisms of the alpha2-adrenergic agonist, clonidine (IT). Chronic, persistent
      inflammatory pain was induced by left hind paw injection of 0.3 ml CFA prepared
      in a mixture with Mycobacterium butyricum. Rats were randomly assigned to groups
      receiving IT clonidine in discrete doses of 1, 10 or 50 microg, 3 or 24 hr post
      inflammation. Measurement of total NOx (NO + NO2- + NO3-) was used to determine
      NO release into the cerebrospinal fluid. Rat thermal antinociception was assessed
      using a radiant heat thermal hyperalgesia model. CFA injection resulted in
      significant thermal hyperalgesia throughout the four days of observation. A dose
      dependent suppression of thermal hyperalgesia and spinal NO release was observed
      after IT clonidine treatment. Evidence from this CFA-induced inflammatory pain
      model suggests that clonidine's spinal antihyperalgesic mechanisms act through
      inhibition of spinal NO release.

PMID- 12184630
TI  - Calcitonin gene-related peptide partially reverses decreased production of
      chemokines KC and MIP-2 following murine sepsis.
AB  - The secretion of calcitonin gene-related peptide (CGRP) and the chemokines KC and
      MIP-2 are increased in the animal models of endotoxemic and septic shock. We
      tested whether CGRP could modulate KC and MIP-2 secretion from different sources
      of macrophages after murine sepsis induced by cecal ligation and puncture (CLP).
      Macrophages were obtained from the peritoneal exudate and lung of female BALB/c
      mice 16 h after CLP and plated in culture with CGRP and/or LPS for 12 h. The
      results showed that peritoneal macrophage production of the chemokines (KC, MIP
      2) and cytokines (TNF-alpha, IL-6) was markedly decreased in CLP mice. Alveolar
      macrophages did not display decreased cytokine/chemokines production after CLP.
      CGRP (0.1 nM-10 nM) partially reversed this decreased production of LPS-induced
      KC and MIP-2 from peritoneal macrophages. These results suggest that CGRP might
      be intimately involved in recruitment of neutrophils by promoting local
      production of the chemokines KC and MIP-2 in murine sepsis.

PMID- 12184631
TI  - Up-regulation of CD13/aminopeptidase N induced by phorbol ester is involved in
      redox regulation and tumor necrosis factor alpha production in HL-60 cells.
AB  - Here, we demonstrate the possible involvement of oxidative stress in altered
      CD13/aminopeptidase N (APN) expression during myeloid cell differentiation
      induced by TPA. In flow cytometrical analysis, CD13/APN protein was
      constitutively expressed in HL-60 cells. When the cells were treated with TPA,
      CD13/APN expression was up-regulated with increased intracellular peroxides and a
      morphological change into macrophage-like cells. This increase in CD13/APN
      expression was suppressed by treatment with N-acetylcysteine. Transfection of Mn
      superoxide dismutase (MnSOD) gene to the cells also suppressed the up-regulated
      CD13/APN expression. Furthermore, a neutralizing antibody to TNFalpha partially
      blocked this up-regulation. These results indicate that the change in
      intracellular redox state could be involved in the up-regulation of CD13/APN
      expression during TPA-induced differentiation of HL-60 cells, suggesting that
      TNFalpha may serve as, at least, one of the signals stimulated by TPA.

PMID- 12184632
TI  - Normal transcription of the C1 inhibitor gene is dependent upon a polypurine
      polypyrimidine region within the promoter.
AB  - Analysis of the transcriptional activity of C1 inhibitor (CIINH) promoter
      reporter constructs with mutations in the R-Y region indicate that triplex
      formation by this region is not a predictor of transcriptional activity and that
      normal promoter function depends on the interaction of trans acting factors with
      specific elements within this region. Electrophoretic mobility shift assay (EMSA)
      of Hep3B nuclear extracts using the wild type promoter probe (nucleotides -98 to 
      9) yielded four major bands. Incubation of the same extracts with probes lacking
      the HNF-1 site resulted in the disappearance of one band. Supershift assays
      indicate that HNF-1alpha is the only previously identified protein that is
      present in the EMSA bands. Southwestern blot analysis detected four bands (M(r)s 
      130, 75, 65 and 20 kDa). These data suggest that the -98 to -9 region of the
      C1INH promoter interacts with at least four proteins, one of which is HNF-1alpha.

PMID- 12184633
TI  - Identification of an occludin cell adhesion recognition sequence.
AB  - The molecular mechanisms by which the tight junction integral membrane protein,
      occludin promotes cell adhesion and establishes an endothelial monolayer
      permeability barrier have not been elucidated. In particular, the amino acid
      sequences of the occludin cell adhesion recognition (CAR) sites have not been
      determined. Here we demonstrate that a cyclic peptide containing the sequence
      LYHY, which is found in the second extracellular domain of occludins in all
      mammalian species, inhibits the establishment of endothelial cell barriers in
      vitro and in vivo. This cyclic peptide also prevents the aggregation of
      fibroblasts stably transfected with cDNA encoding occludin. The data suggest that
      the LYHY motif is an occludin CAR sequence.

PMID- 12184634
TI  - Anti-inflammatory effect of granulocyte and monocyte adsorption apheresis in a
      rabbit model of immune arthritis.
AB  - In active rheumatoid arthritis, large numbers of granulocytes and macrophages are
      found in the inflamed joints. These leucocytes can promote inflammation and
      tissue injury by releasing inflammatory cytokines, proteinases and oxygen
      derivatives. To see if granulocyte and monocyte (GM) depletion produces anti
      inflammatory effect, GM adsorption apheresis was performed in rabbits with immune
      arthritis by using a column (Adacolumn) filled with cellulose diacetate beads (G
      1 beads) as adsorptive carriers which selectively adsorb CD11b positive GMs.
      Injection of ovalbumin into the knee joints of ovalbumin-sensitized rabbits
      caused a marked increase in peripheral blood leucocytes, joint swelling,
      increased granulocyte adhesion to G-1 beads and elevated TNF-alpha production by
      peripheral blood mononuclear cells (PBMC). When rabbits received a 60 min
      adsorption apheresis, there was suppression of CD11b positive leucocyte
      infiltration into the joint and reduced joint swelling (P < 0.01) compared with
      controls. Additionally, there was a significant (p < 0.01) suppression of TNF
      alpha production by PBMC in the post column blood. These results suggest that GM
      depletion may serve as a non-pharmacological strategy to modify inflammatory
      disorders.

PMID- 12184635
TI  - Blood thiols and malondialdehyde levels in psoriasis.
AB  - Forty patients with psoriasis and forty healthy controls were enrolled to study
      the levels of total blood thiols (an important part of the body's antioxidant
      defence system) and plasma malondialdehyde (a lipid peroxidation product). The
      levels of total blood thiols in psoriatic patients in the acute phase were
      significantly lower than those in controls, but total blood thiol levels in
      psoriatic patients in the remission phase were not significantly different from
      those in controls. There was a significant difference between levels of total
      blood thiols of patients in the acute phase and in remission. The levels of
      plasma MDA were significantly raised in psoriatic patients in the acute phase as
      compared to those in controls and in patients in remission. The differences in
      levels of plasma MDA were not significant between control subjects and patients
      in remission. These findings suggest a role of oxidative stress in the
      etiopathogenesis of psoriasis.

PMID- 12184636
TI  - Detection of herpes simplex virus DNA in serum and oral secretions during acute
      recurrent herpes labialis.
AB  - Although herpes simplex virus (HSV) has been detected in the peripheral blood of
      immunocompromised patients and in neonates with disseminated disease, the extent
      to which the virus may be present in the blood during a localized infection in
      otherwise healthy patients is still unknown. Literature on patterns of HSV
      shedding into the oral cavity at the prodromal stage of the disease, during
      recurrences, and also during asymptomatic periods is still lacking. The present
      study aims at the detection of HSV DNA in the serum and oral secretions during
      acute herpes labialis using a highly sensitive technique, the polymerase chain
      reaction (PCR). The study included 10 patients with acute herpes labialis and
      five healthy controls. Using PCR, herpes simplex virus DNA was detected in the
      serum of seven patients (70%) and in the saliva of nine patients (90%). One of
      the control cases showed positive HSV DNA in the saliva (20%). There was good
      statistical agreement between the presence of HSV DNA in the serum and saliva.
      Frequency of attacks, patient's age, and gender had no statistically significant
      effect on the presence of the virus in serum or in saliva. It is concluded that
      HSV viremia during attacks of recurrent herpes simplex is more frequent than
      previously appreciated.

PMID- 12184637
TI  - A study from Nepal showing no correlation between lichen planus and hepatitis B
      and C viruses.
AB  - A total number of 86 cases of Lichen planus (LP) were seen over a period of one
      and a half years. This constituted 0.58% of 14,833 new dermatological patients
      seen. Hepatitis B and C viral (HBV & HCV) serology was carried out in 64 patients
      and 43 age and sex matched controls. In the examined patients, 35 (54.27%) had
      the skin lesions only. Oral lesions were present in 15 (23.4%) of the patients in
      addition to skin lesions, while 14 (21.9%) had only oral involvement. Serology
      for HBsAg and HCV was negative in all types of LP patients and the controls. In
      Nepal, HBV and HCV seem to be not important in the pathogenesis of LP.

PMID- 12184638
TI  - Effect of two consecutive earthquakes on outbreaks of alopecia areata.
AB  - The pathogenesis of alopecia areata (AA) is still unknown. We investigated
      whether two consecutive earthquakes in Duzce, Turkey within a 3-month interval
      could precipitate AA. Patients who developed AA after the first earthquake in
      Duzce were included in this study. The admittance rate and demographic
      characteristics of AA patients admitted in the same period of the previous year
      (BE=before earthquake group) were compared to that of AA patients admitted after
      the earthquake (AE=after earthquake group). The admittance rate and onset of AA
      after the first earthquake were investigated retrospectively. In addition,
      possible relationships between the earthquake and age at the first attack,
      severity of the disease, and ophiasis were studied. The ratio of AA patients in
      the BE group was 12/1,121 (0.9%), while this value was 26/1,430 (1.8%) in the AE
      group (p=0.07). There were no significant differences with regard to sex, age of
      the first attack, severity of the disease, or ophiasis between the two groups. AA
      appeared between 18-28 weeks after the first earthquake in 14 (53.8%) of the
      patients. The earthquake did not increase the admittance rate of AA
      significantly. This finding suggests that a stressful event such a natural
      disaster is not a unique factor in AA outbreaks.

PMID- 12184639
TI  - Frictional hair loss in Iraqi patients.
AB  - A total of 50 Iraqi male patients with frictional hair loss were studied. Their
      ages ranged from 27-55 years with a mean +/- SD of 40.60 +/- 7.82 years. The age
      of onset ranged from 26-50 years with a mean +/- SD of 38 +/- 7.3 years. The
      duration of disease was 1-5 years, mean +/- SD 2.2 +/- 1.3. Middle age was the
      most common age group affected. Patterns of hair loss were as follows; bilateral
      thighs & legs 13 (26%), bilateral thighs alone in 9 patients (18%), bilateral
      shins & calves (legs) in 4 patients (8%), abdomen alone in 8 patients (16%),
      thigh and abdomen 4 (8%) patients, legs & abdomen 4 (8%) patients, and all sites
      in 12 patients (24%). The pattern of patchy hair loss showed some etiological
      preference. It was found to be due to continuous pressure from socks, trousers
      and bed. Skin biopsies from five patients showed apparently normal histology.
      Twenty-six (52%) of the cases were healthy. There were no important medical or
      dermatological associations, such as alopecia areata or peripheral neuropathy in
      any patient although unrelated medical conditions were seen in 24 (48%). To the
      best of our knowledge, this type of patchy hair loss has attracted very little
      attention in the past, and the literature appeared to be deficient in references
      to this problem.

PMID- 12184640
TI  - Pseudoxanthoma elasticum (PXE)-like calcification in adult dermatomyositis.
AB  - A case of pseudoxanthoma elasticum (PXE)-like calcification in adult
      dermatomyositis (DM) is described. The patient was a 38-year-old woman with a
      history of dermatomyositis for 3 months. Yellowish, hard, papulo-plaque lesions,
      which looked like those of pseudoxanthoma elasticum, were noted on her left
      axilla. Calcium deposition was confirmed by X-ray, histopathological, and
      electron microscopic examinations. Histopathological and histochemical
      examinations showed acicular calcium deposition in the middle and deep dermis
      surrounded by mucin. Electron microscopic examination revealed that the calcium
      deposition was not on collagen fibers. These morphological features were distinct
      from those of PXE. We proposed the possibility that degenerated mucin or
      degenerated elastic fiber might result in subsequent calcium deposition in
      reticular calcinosis in adult DM. The calcification clinically disappeared
      without any specific treatment except for prednisolone and cyclophosphamide.

PMID- 12184641
TI  - A case of tufted hair folliculitis.
AB  - A 35-year-old man developed red papules and plaques with alopecia and hair tufts
      on the parietal and occipital areas of his scalp. Each tuft was comprised of 5 to
      25 hairs arising from individual hair follicules. Histopathological findings
      showed a dense infiltration of plasma cells in the dermis. Based on these
      findings, he was diagnosed as tufted hair folliculitis. Oral minocycline and
      topical gentamicin were not effective, but the patient responded well to four
      weeks of oral refampicin.

PMID- 12184642
TI  - A case of disseminated and recurrent infundibulofolliculitis responsive to
      treatment with systemic isotretinoin.
AB  - We report a 16-year-old Turkish patient who developed disseminated and recurrent
      infundibulofolliculitis (DRIF) and responded well to systemic isotretinoin
      therapy after three months.

PMID- 12184644
TI  - Familial amyloidosis cutis dyschromica: six cases from three families.
AB  - Amyloidosis cutis dyschromica, a rare form of primary cutaneous amyloidosis
      requiring histopathological confirmation, is characterized by generalized,
      asymptomatic hyperpigmentation intermingled with several hypopigmented spots
      without papulation, atrophy, and telangiectasia. Its onset usually begins before
      puberty. We describe six patients from three families, four male and two female.
      The mean age at onset was 10.2 years. Although the skin eruptions had developed
      extensively since childhood, systemic involvement was not evident even after long
      term follow-up. Due to its unique and characteristic features, this condition
      should be considered as a separate entity and differentiated from other variants
      of primary cutaneous amyloidosis. The familial occurrence in our report suggests
      a genetic causal factor in this disease.

PMID- 12184643
TI  - Unilateral generalized morphea in childhood.
AB  - We report a 6-year-old boy with unilateral generalized morphea distributing on
      the right side of his lower leg, trunk, and upper arm. A skin biopsy from the
      right thigh showed accumulation of thick collagen bundles extending from the
      middle dermis to the subcutaneous fat tissue. The levels of antinuclear
      antibodies, rheumatoid factor, and anti single-stranded DNA antibody were
      elevated. No severe deformity or functional disabilities were noted. With topical
      corticosteroid therapy, the sclerotic skin became gradually softer, and no
      progression of sclerosis has been noted for one year.

PMID- 12184645
TI  - Hyperpigmentation due to pyrimethamine use.
AB  - Pyrimethamine is used for the treatment of toxoplasmosis and the prophylaxis of
      malaria. Among the well-documented side effects are megaloblastic anemia,
      leukopenia, thrombopenia, rash, vomiting, and diarrhea. Hyperpigmentation is a
      very rare side effect. In some patients, associated HIV infection makes it
      difficult to distinguish the reasons for the etiology. We herein describe an HIV
      negative patient who developed hyperpigmentation after pyrimethamine use.

PMID- 12184646
TI  - Arsenic keratosis and pigmentation accompanied by multiple Bowen's disease and
      genitourinary cancer in a psoriasis patient.
AB  - We report a case of arsenic keratosis and pigmentation accompained by multiple
      Bowen's disease and genitourinary cancer in a 64-year-old man. He was a psoriasis
      patient with a history of herbal medication for about thirty years. He showed
      multiple hyperkeratotic plaques on the bilateral palms, soles, and multiple,
      brownish, scaly, elevated papules on the back in addition to diffuse
      hyperpigmentation. Biopsy confirmed arsenic keratosis and Bowen's disease.
      Transitional cell carcinoma was also detected on his ureter and bladder during
      follow-up. The skin lesions were treated with topical 5-fluorouracil, etretinate,
      and excision with improvement.

PMID- 12184648
TI  - Induction of Darier's disease by repeated irradiation by ultraviolet B;
      protection by sunscreen and topical ascorbic acid.
AB  - Darier's disease, keratosis follicularis, is frequently aggravated by sun
      exposure. Although there have been reports of Darier's disease reproduced by
      repeated exposure to ultraviolet B, little is known about its photo-protection.
      We artificially induced Darier's disease in a 47-year-old Korean man, and tested
      the protection afforded by sunscreen and topical ascorbic acid. Complete lesions
      of Darier's disease arose with repeated exposure of ultraviolet B (2,600 mJ/cm2
      for 10 days), and sunscreen and topical ascorbic acid protected against its
      appearance. This result strongly suggests that sunscreen and ascorbic acid would
      be very helpful in preventing the aggravation of Darier's disease caused by sun
      exposure.

PMID- 12184649
TI  - Prevalence of oral lichen planus in a group of hepatitis C patients.

PMID- 12184647
TI  - Levofloxacin alone efficiently treated a cutaneous mycobacterium fortuitum
      infection.
AB  - Cutaneous infections with Mycobacterium (M.) fortuitum are rare, and some cases
      resist treatment. We report two cases of cutaneous M. fortuitum infection
      successfully treated with levofloxacin alone.

PMID- 12184650
TI  - Becker's nevus on the lower extremity: an uncommon site.

PMID- 12184651
TI  - A case of burn due to sadomasochism.

PMID- 12184652
TI  - Phenolyc glycolipid-1 found in tissues infected by Mycobacterium ulcerans.

PMID- 12184653
TI  - Intrahospital transport of the adult mechanically ventilated patient.
AB  - As the diagnosis and treatment of critically ill patients continues to advance,
      the frequency of intrahospital transport of ventilator-dependent patients
      increases. Once the risks and benefits of transport are established, even the
      sickest ICU patient can be transported safely when adequate time is taken and
      preparations are made before beginning the transport. Patients should be
      stabilized as much as possible and monitored before, during, and after transport.
      Those responsible for the patient should be trained to provide a safe outcome.
      This necessitates that caregivers receive education in patient evaluation,
      potential risks, complications, interventions, equipment operation, and
      troubleshooting that may be necessary when caring for ventilated patients outside
      the ICU. All members of the transport team should communicate effectively and be
      aware of their roles in the transport process to minimize delays and mishaps
      during transport and at the final destination. Written policies that define the
      level of personnel, level of training, level of support, and equipment necessary
      can facilitate the transport process. When choosing a device to provide
      ventilation, the patient's clinical condition should be determine which method is
      used for transport.

PMID- 12184654
TI  - Training for the transport of mechanically ventilated patients.
AB  - The transport of critically ill patients is hazardous, yet necessary. In these
      conditions monitoring may be challenging, and the ability to intervene when
      problems arise is often limited. Conducting safe transport of these patients has
      been shown to be possible when experienced personnel apply their knowledge
      appropriately. It is a complex exercise, however, with significant potential for
      breakdown. Despite the magnitude of such transports of high-risk patients, no
      substantive focus on formal training exists. This article proposes that formal
      training of transport teams be strongly considered at the institutional level,
      and it introduces the content and method of delivery of this training. Because
      these are expressed opinions, the concept should be explored and validated by an
      interventional study, establishing a baseline of transport complications in a
      given facility, implementing some form of training, and reevaluating the
      performance of the trained providers in the same institution. A significant
      reduction in complications would validate the time, effort, and expense of
      developing such a course and would provide a model for other institutions to
      follow.

PMID- 12184655
TI  - Transport ventilators.
AB  - Today there are a number of automatic resuscitators and simple and complex
      transport ventilators on the market. The user must consider the purpose of the
      device, the patient population to be ventilated and the capabilities of the
      individual devices before purchasing a transport ventilator.

PMID- 12184656
TI  - Interhospital transport of the adult mechanically ventilated patient.
AB  - Interhospital transport of the adult mechanically ventilated patient may be
      necessary for those who require specialized care. An experienced medical team can
      safely transport even the most critically ill patients if the care is optimized
      before departure. Patients with severe respiratory failure may have to remain on
      an ICU ventilator throughout the transport period, depending on the specific
      transport ventilator. Near-terminal ARDS can be treated with ECLS, and these
      patients also may be safely transported to a regional center.

PMID- 12184657
TI  - Mechanical ventilation during long-range air transport.
AB  - Mechanical ventilation during long-range aeromedical transport presents
      significant challenges. Patient, crew member, and equipment are placed in an
      environment with reduced barometric pressure, noise, vibration, and limited
      space, oxygen, electrical power, and access to imaging technology. It is the
      transport team's responsibility to provide care in this environment, which
      approximates that given in the ICU as closely as possible. This is achieved
      through careful preparation and planning. Preparation starts with training of the
      personnel and selection of optimal equipment. Planning needs to consider the
      patient's physiologic reserve, available supplies of oxygen and electrical power,
      and the crew's ability to sustain high performance for the duration of the
      mission.

PMID- 12184658
TI  - Transport of the mechanically ventilated neonate.
AB  - Although the primary focus of this article is on interhospital transport, some of
      the same basic transport principles and management techniques apply to
      intrahospital transport. The level of care provided during interhospital and
      intrahospital transport should be based on the neonate's diagnosis, clinical
      status, anticipated problems, and local, state, and national standards and
      regulations. The transport team should have policies and procedures to direct
      their practice. Documentation of the transport process should be initiated with
      the referral call and continued until the completion of transport. Planning and
      anticipation of problems are essential, as is care of the family. The transport
      team should evaluate each neonate's individual response to the transport.

PMID- 12184660
TI  - Issues in the design and implementation of psychoneuroimmunology research.
AB  - Research that uses a psychoneuroimmunology (PNI) framework seeks to determine
      whether valid associations exist among stress, immune function, and health. These
      associations are difficult to conclusively determine due to the fact that PNI
      research is fraught with methodological difficulties. These difficulties arise
      from the multifaceted and complex nature of the neuro-endocrine-immune network
      that is the phenomenon of interest in PNI. This article discusses multiple issues
      of which investigators should be aware when designing and implementing PNI
      research including (1) the control of potentially immunomodulating variables
      related to demographics, behavior, and lifestyle; (2) the manner in which stress,
      endocrine function, immunity, and health outcomes are measured in consideration
      of the theoretical relevance to the research question, population, or disease
      entity understudy; (3) the way physiological specimens are procured and stored;
      and (4) the methods by which assays are performed.

PMID- 12184659
TI  - Transport of the mechanically ventilated pediatric patient.
AB  - Children deserve quality care when they are critically ill or injured.
      Specialized pediatric services may be limited outside major medical centers.
      Transport by specialized pediatric and neonatal transport teams may be required
      to deliver patients to tertiary pediatric medical centers. In addition, in the
      past decade a cost-effective, organized, systematic approach to health care
      management has assumed greater importance, leading to the concept of the so
      called medical home. In this model, a child with a complex medical problem is
      cared for in the environment in which he or she will receive the best care, with
      emphasis on providing rehabilitative and long-term care near the child's home. It
      is likely, then, that the field of pediatric transport medicine will assume
      greater importance in the coming decade.

PMID- 12184661
TI  - Evaluation of variables to characterize respiratory periodicity during sleep in
      older adults.
AB  - Reliable markers of early neurological decline might guide interventions to
      prevent or reverse cognitive decline in older adults. Because cognitive decline
      is associated with hypoxemia during sleep, the authors examined 3 respiratory
      periodicity variables in 5 older adults. Subjects were monitored overnight using
      standard polysomnography. From the inductance band signal, the authors calculated
      the variability in duration of breathing cycles measured by standard deviation of
      interbreath intervals (sdIBI), frequency of breathing cycles measured by standard
      deviation of interbreath frequencies (sdIBF), and amplitude of breathing cycles
      measured by standard deviation of breathing cycle amplitudes (sdAMP). Logistic
      regression analysis and kappa coefficients identified variables that reliably
      detected 5-minute segments having central or obstructive apneas or body
      movements. An sdIBF > or = 4.5 cpm identified body movements (sensitivity = 0.96,
      specificity = 0.96, kappa = 0.90). An sdIBI > 1.2 seconds identified central
      apneas (sensitivity = 0.86, specificity = 0.99, kappa = 0.86), and an sdIBI > or
      = 1.68 seconds identified segments with 3 central apneas (sensitivity = 0.90,
      specificity = 0.89, kappa = 0.89). An sdAMP > or = 0.1 V and an sdIBF > or = 1.5
      cpm identified obstructive apneas (kappa = 0.91). Data support the potential of
      these variables to identify central and obstructive apneas and to classify
      individuals according to different patterns of respiratory periodicity.

PMID- 12184662
TI  - Amlodipine decreases iron uptake and oxygen free radical production in the heart
      of chronically iron overloaded mice.
AB  - Hereditary hemochromatosis is a disorder of iron metabolism, which is currently
      the most prevalent autosomal recessive disorder in the world, with an expression
      of the homozygous form occurring in approximately 1 in 200 individuals of
      European descent. Approximately one third of patients with hemochromatosis die of
      iron-induced cardiac complications. Although the exact mechanism is not known, it
      is believed that the toxicity of excess iron in biological systems is due to its
      ability to catalyze the generation of harmful reactive oxygen free radical
      species (ROS), which can damage proteins, lipids, and DNA. There is preliminary
      evidence to suggest that non-transferrin-bound iron uptake in the myocardium may
      occur through voltage-dependent L-type calcium channels, and that calcium channel
      blockers (CCBs) may possess antioxidant properties. Accordingly, the authors
      hypothesized that the administration of amlodipine besylate would (1) decrease
      iron uptake in the myocardium and (2) decrease oxygen free radical production as
      measured by cytotoxic aldehyde-derived peroxidation products in a murine model of
      iron overload cardiomyopathy. The findings show that the CCB amlodipine is
      partially effective in limiting iron uptake in the heart and significantly
      inhibits the production of ROS in chronically iron-loaded mice. These are
      important preliminary findings because they suggest that CCBs may have
      significance in the clinical management of genetic disorders of iron metabolism.

PMID- 12184663
TI  - The effect of opioid antagonism on food intake behavior and body weight in a
      biobehavioral model of obese binge eating.
AB  - The obese Zucker rat (OZR) exhibits a hyperphagic eating pattern similar to the
      obese binge eater. Dynorphin, an endogenous agonist of the kappa receptor, is
      associated with regulation offood intake. Lessened sensitivity to opioid
      antagonists and/or increased central dynorphin levels may contribute to the
      hyperphagic eating pattern observed in the OZR. This study examined the temporal
      effect of a single intracerebroventricular (ICV) dose of nor-binaltorphimine
      (NBNI), a specific and long-lasting kappa opioid antagonist, on food intake, body
      weight, and satiety measures (meal size and the shape of the cumulative food
      intake curve [CFIC]) in adult male OZRs. Analysis of individual subjects revealed
      a differential response to opioid antagonism with respect to weight loss,
      reduction in food intake, and change in the slope of the CFIC, with some
      responding and others responding poorly. Repeated-measures analysis of variance
      showed a significant decrease in body weight (P = 0.001) and food intake (P =
      0.03) in responders compared to poor responders and controls. Satiation was
      influenced to a greater extent in responders, who showed a significant reduction
      in meal size and a greater change in the CFICfor the largest meal of the day
      toward a pattern of satiation. These data suggest that a differential response to
      chronic opioid antagonism may exist in the OZR.

PMID- 12184664
TI  - Functional versus fractional oxygen saturation readings: bias and agreement using
      simulated solutions and adult blood.
AB  - The purpose of this study was to examine the bias and agreement between
      functional oxygen saturation (SO2) and fractional oxyhemoglobin (HbO2) using
      simulated quality control (QC) solutions and adult blood. Using a hemoximeter, 5
      analysts performed at least 5 tests each on QC solutions with 3 different
      hemoglobin (Hb) levels and on adult blood samples of various oxygen saturation
      levels representing venous or arterial samples. Bias and the limits of agreement
      were determined using the technique of Bland and Altman. Using QC solutions with
      low, normal, and high Hb levels, the bias for SO2 against HbO2 was 20.82 +/- 0.50
      (n = 66), 19.14 +/- 0.56 (n = 81), and 19.59 +/- 0.43 (n = 79), respectively,
      with SO2 reading consistently higher. The correlation between SO2 and HbO2 was 
      0.49, -0.69, and -0.68, respectively. Using adult blood, the bias for SO2 against
      HbO2 was 1.29 +/- 0.48 for venous samples (n = 62) and 1.9 +/- 0.19 for fully
      oxygenated samples (n = 36), and the correlation between SO2 and HbO2 was 1.0 and
      0.68, respectively. These findings suggest that the consistency between the
      measurements of SO2 and HbO2 may be dependent on hemoglobin levels and
      oxygenation status. Thus, caution is warranted when assuming that the
      measurements of SO2 and HbO2 are interchangeable.

PMID- 12184665
TI  - Predictors of fatigue in healthy young adults: moderating effects of cigarette
      smoking and gender.
AB  - Fatigue is a common complaint of patients seen in primary care. Factors that
      contribute to fatigue in a patient population include poor health status,
      psychological stress, poor nutrition, and pregnancy. Less well understood are
      factors that contribute to fatigue among healthy, nonpregnant individuals. Within
      the framework of the theory of unpleasant symptoms, 40 healthy young smoking and
      nonsmoking adults between the ages of 18 and 35 were evaluated to determine self
      report level of fatigue and contributing physiological, psychological, and
      situational factors. Results indicate that while self-report of fatigue did not
      vary in this population based on gender, subjects who were moderate to heavy
      cigarette smokers were significantly more fatigued than were nonsmokers (F =
      10.24, df = 1, 38, P < 0.01), with the effect being specific to male smokers.
      Self-report of fatigue did not correlate with body mass index, baseline
      inflammatory or immune status, or blood pressure. Positive psychological and
      situational predictors of fatigue included depression (r = 0.556, P < 0.001),
      state anxiety (r = 0.569, P < 0.001), sleep quality (r = -0.399, P < 0.05), and
      sleep quantity (r = -0.411, P < 0.05). These results suggest that psychological
      and situational factors are key contributors to fatigue in young adults and that
      smoking is a risk factor for fatigue in men.

PMID- 12184666
TI  - Glabellar gala.

PMID- 12184667
TI  - Epidermolysis bullosa simplex.
AB  - Blistering is a common occurrence generally caused by moderate or repetitive
      trauma to the skin. Blistering due to minor trauma is less common and may be
      associated with a group of heterogeneous genetic diseases called epidermolysis
      bullosa (EB). The level of vesiculation within the skin defines 3 major subtypes
      of EB: EB simplex (EBS), dystrophic EB, and junctional EB. We will review the
      simple type-EBS.

PMID- 12184668
TI  - Photo quiz. Palisaded neutrophilic and granulomatous dermatitis with underlying
      Wegener's granulomatosis.

PMID- 12184669
TI  - Aquatic antagonists: Catalaphyllia jardinei sting.
AB  - Catalaphyllia jardinei is a blue-green soft coral whose red-violet tipped
      tentacles have made it a very colorful, popular animal prized by amateur
      aquarists (Figure 1). Its normal habitat is the Indo-Pacific area from Seychelles
      through Vanuatu and from Northern Australia to Southern Japan. It is regarded as
      mildly venomous. However, to our knowledge, no reports exist on its sting's
      effects on man.

PMID- 12184670
TI  - Berloque dermatitis induced by "Florida water".
AB  - Phytophotodermatitis is a phototoxic dermatitis resulting from contact with
      psoralen-containing plants such as celery, limes, parsley, figs, and carrots.
      Berloque dermatitis is a variant of phytophotodermatitis and is caused by high
      concentrations of psoralen-containing fragrances, most commonly oil of bergamot.
      Berloque dermatitis is rarely seen today because of the removal of these
      fragrances from most cosmetic products in the United States. We report, however,
      a group of patients still at risk for berloque dermatitis. These patients use the
      colognes "Florida Water" and "Kananga Water," which are popular in Hispanic,
      African American, and Caribbean populations. These fragrant waters are used for
      spiritual blessing, treating headaches, and personal hygiene.

PMID- 12184671
TI  - Bullous systemic lupus erythematosus with milia and calcinosis.
AB  - Bullous systemic lupus erythematosus (SLE) is a rare skin manifestation of SLE.
      It shares many features with epidermolysis bullosa acquisita (EBA). We report on
      a patient with SLE who developed a vesiculobullous eruption followed by findings
      not typical in bullous SLE, namely milia, mild scarring, and calcinosis. We
      discuss the relationship between bullous SLE and EBA.

PMID- 12184672
TI  - Yellow urticaria secondary to hyperbilirubinemia in a patient with end-stage
      liver disease.
AB  - Acute urticaria is characterized by pruritic, erythematous, edematous plaques. We
      report the case of a 48-year-old man with acute urticaria, whose lesions appeared
      yellow secondary to an elevated bilirubin level.

PMID- 12184673
TI  - Papular pityriasis rosea.
AB  - Pityriasis rosea (PR) is a seasonal papulosquamous disorder that can be easily
      confused with a wide variety of similar appearing cutaneous disorders. This is
      particularly evident in its atypical papular form. We present a case report of
      atypical papular PR, along with a discussion of clinical presentation, histologic
      criteria, proposed etiology, and treatment options. Papular PR is atypical,
      presenting in a minority of patients, and may pose a diagnostic challenge. Being
      familiar with these atypical characteristics will facilitate accurate and timely
      diagnosis.

PMID- 12184674
TI  - Kimura disease: 2 case reports and a literature review.
AB  - Kimura disease (KD) is a chronic inflammatory soft-tissue disorder often
      presenting as swollen soft tissue or enlarged lymph nodes. KD is rare, and most
      reported cases have involved Asians. The pathogenesis is poorly understood, and
      treatments are unsatisfactory. KD is associated with allergic conditions such as
      asthma, rhinitis, and eczema. We present the cases of 2 patients treated for
      chronic endogenous eczema and KD in our dermatology clinic.

PMID- 12184675
TI  - Erythema dyschromicum perstans: a case report and review.

PMID- 12184676
TI  - Familial partial lipodystrophy.
AB  - The lipodystrophies are rare disorders characterized by insulin resistance and
      the absence or loss of body fat. The 4 subtypes of lipodystrophy are
      characterized by onset and distribution. Partial lipodystrophy is rare, with loss
      of fat from the extremities and excess fat accumulation in the face and neck;
      recognizing this phenotype and subsequent referral for endocrinologic care may
      improve outcome and reduce mortality.

PMID- 12184677
TI  - Disseminated coccidioidomycosis discovered during routine skin cancer screening.
AB  - A 78-year-old white man presented for routine dermatologic examination. A 4x4-mm
      erythematous papule was noted on the left upper back. It was asymptomatic and
      previously unnoticed by the patient. The results of a shave biopsy revealed a
      large spherule with granular cytoplasm diagnostic of coccidioidomycosis. Chest x
      ray revealed a 1.8-cm right upper lobe mass. The complement fixation antibody
      titer for cocci was 1:128. The patient was treated for disseminated
      coccidioidomycosis with oral fluconazole. The epidemiology, diagnosis, and
      management of coccidioidomycosis are discussed.

PMID- 12184679
TI  - Healing or hustling?

PMID- 12184678
TI  - Blaschkoid eccrine spiradenomas.
AB  - We report a case of multiple eccrine spiradenomas that arose in adulthood along a
      patient's arm and continued to the midline of the patient's chest across multiple
      dermatomes. This is one of a handful of such cases, which have been reported as
      linear, nevoid, or zosteriform eccrine spiradenomas. We believe this distribution
      is best described as Blaschkoid rather than zosteriform or linear because these
      lesions follow the lines of Blaschko rather than those of a single dermatome.

PMID- 12184680
TI  - Gifting one's estate to dentistry.

PMID- 12184681
TI  - California's colorful quilt of care stitched with compassion.

PMID- 12184682
TI  - Dental schools teach philosophy of service.

PMID- 12184683
TI  - California dentists give time and money to New York.

PMID- 12184684
TI  - Securing grants for charitable efforts.

PMID- 12184686
TI  - 1-800-MY-MOLAR.

PMID- 12184685
TI  - Tin Man's promise.

PMID- 12184687
TI  - A mechanism for mercury oxidation in coat-derived exhausts.
AB  - This paper evaluates an elementary reaction mechanism for Hg0 oxidation in coal
      derived exhausts consisting of a previously formulated homogeneous mechanism with
      102 steps and a new three-step heterogeneous mechanism for unburned carbon (UBC)
      particles. Model predictions were evaluated with the extents of Hg oxidation
      monitored in the exhausts from a pilot-scale coal flame fired with five different
      coals. Exhaust conditions in the tests were very similar to those in full-scale
      systems. The predictions were quantitatively consistent with the reported coal
      quality impacts over the full range of residence times. The role of Cl atoms in
      the homogeneous mechanism is hereby supplanted with carbon sites that have been
      chlorinated by HCl. The large storage capacity of carbon for Cl provided a source
      of Cl for Hg oxidation over a broad temperature range, so initiation was not
      problematic. Super-equilibrium levels of Cl atoms were not required, so Hg was
      predicted to oxidize in systems with realistic quench rates. Whereas many
      fundamental aspects of the heterogeneous chemistry remain uncertain, the
      information needed to characterize Hg oxidation in coal-derived exhausts is now
      evident: complete gas compositions (CO, hydrocarbons, H2O, O2 NOx, SOx), UBC
      properties (size, total surface area), and the ash partitioning throughout the
      exhaust system are required.

PMID- 12184688
TI  - Assessing sorbents for mercury control in coal-combustion flue gas.
AB  - Sorbent injection for Hg control is one of the most promising technologies for
      reducing Hg emissions from power-generation facilities, particularly units that
      do not require wet scrubbers for SO2 control. Since 1992, EPRI has been assessing
      the performance of Hg sorbents in pilot-scale systems installed at full-scale
      facilities. The initial tests were conducted on a 5,000-acfm (142-m3/min) pilot
      baghouse. Screening potential sorbents at this scale required substantial
      resources for installation and operation and did not provide an opportunity to
      characterize sorbents over a wide temperature range. Data collected in the
      laboratory and in field tests indicate that sorbents are affected by flue gas
      composition and temperature. Tests carried out in actual flue gas at a number of
      power plants also have shown that sorbent performance can be site-specific. In
      addition, data collected at a field site often are different from data collected

PMID- 12184689
TI  - The fate and behavior of mercury in coal-fired power plants.
AB  - For the past 22 years in the Netherlands, the behavior of Hg in coal-fired power
      plants has been studied extensively. Coal from all over the world is fired in
      Dutch power stations. First, the Hg concentrations in these coals were measured.
      Second, the fate of the Hg during combustion was established by performing mass
      balance studies. On average, 43 +/- 30% of the Hg was present in the flue gases
      downstream of the electrostatic precipitator (ESP; dust collector). In individual
      cases, this figure can vary between 1 and 100%. Important parameters are the Cl
      content of the fuel and the flue gas temperature in the ESP. On average, 54 +/-
      24% of the gaseous Hg was removed in the wet flue-gas desulfurization (FGD)
      systems, which are present at all Dutch coal-power stations. In individual cases,
      this removal can vary between 8% (outlier) and 72%. On average, the fate of Hg
      entering the power station in the coal was as follows: <1% in the bottom ash, 49%
      in the pulverized fuel ash (ash collected in the ESP), 16.6% in the FGD gypsum,
      9% in the sludge of the wastewater treatment plant, 0.04% in the effluent of the
      wastewater treatment plant, 0.07% in fly dust (leaving the stack), and 25% as
      gaseous Hg in the flue gases and emitted into the air. The distribution of Hg
      over the streams leaving the FGD depends strongly on the installation. On
      average, 75% of the Hg was removed, and the final concentration of Hg in the
      emitted flue gases of the Dutch power stations was only -3 microg/m3(STP) at 6%
      O2. During co-combustion with biomass, the removal of Hg was similar to that
      during 100% coal firing. Speciation of Hg is a very important factor. An oxidized
      form (HgCl2) favors a high degree of removal. The conversion from Hg0 to HgCl2 is
      positively correlated with the Cl content of the fuel. A catalytic DENOX (SCR)
      favors the formation of oxidized Hg, and, in combination with a wet FGD, the
      total removal can be as high as 90%.

PMID- 12184690
TI  - Full-scale evaluation of mercury control with sorbent injection and COHPAC at
      Alabama Power E.C. Gaston.
AB  - The overall objective of this project was to determine the cost and impacts of Hg
      control using sorbent injection into a Compact Hybrid Particulate Collector
      (COHPAC) at Alabama Power's Gaston Unit 3. This test is part of a program funded
      by the U.S. Department of Energy's National Energy Technology Laboratory (NETL)
      to obtain the necessary information to assess the costs of controlling Hg from
      coal-fired utility plants that do not have scrubbers for SO2 control. The
      economics will be developed based on various levels of Hg control. Gaston Unit 3
      was chosen for testing because COHPAC represents a cost-effective retrofit option
      for utilities with existing electrostatic precipitators (ESPs). COHPAC is an EPRI
      patented concept that places a high air-to-cloth ratio baghouse downstream of an
      existing ESP to improve overall particulate collection efficiency. Activated
      carbons were injected upstream of COHPAC and downstream of the ESP to obtain
      performance and operational data. Results were very encouraging, with up to 90%
      removal of Hg for short operating periods using powdered activated carbon (PAC).
      During the long-term tests, an average Hg removal efficiency of 78% was measured.
      The PAC injection rate for the long-term tests was chosen to maintain COHPAC
      cleaning frequency at less than 1.5 pulses/bag/hr.

PMID- 12184691
TI  - Release of mercury vapor from coal combustion ash.
AB  - The long-term stability of Hg in coal combustion by-products (CCBs) was evaluated
      at ambient and near-ambient temperatures. Six CCB samples with atypically high
      levels of total Hg were selected for study assuming a greater potential for
      release of measurable amounts of Hg vapor. The samples selected included two fly
      ash samples from U.S. eastern bituminous coal, two fly ash samples from South
      African low-rank coal, one fly ash from Powder River Basin (PRB) subbituminous
      coal blended with petroleum coke, and one PRB subbituminous coal fly ash
      incorporated with flue gas desulfurization material. Air scrubbed of Hg was
      passed through compacted 100-g aliquots of each sample at 1 mL/min and vented to
      a gold-coated quartz trap to collect released Hg vapor. The samples were
      maintained at ambient and near-ambient (37 degrees C) temperatures. All samples
      released low-picogram levels of Hg after 90 days. No pattern was evident to link
      the total Hg content to the rate of release of Hg vapor. An average of 0.030 pg
      Hg/g CCB/day was released from the samples, which equates to 2.2 x 10(-8) lb
      Hg/ton CCB/year. If this were applied to a coal-fired power plant production of
      200,000 tons of fly ash per year, there would be a maximum potential release of
      0.0044 lb, or 2.00 g, of Hg per year. Experiments are continuing to determine
      long-term vapor release of Hg from CCBs. All samples have been set up in
      duplicate at ambient temperature with an improved apparatus to reevaluate results
      reported in this article.

PMID- 12184692
TI  - Control of mercury emissions from a municipal solid waste incinerator in Japan.
AB  - The control of Hg emissions from a municipal solid waste incinerator (MSWI) is
      very important, because more than 78% of municipal solid waste (MSW) is
      incinerated. The Hg content of coal used in utility boilers is relatively low in
      Japan. In this study, recent trends in the Hg content of MSW in Japan and
      activated carbon (AC) injection as a control technology of Hg emission from an
      MSWI are discussed. The effect of AC injection on Hg removal from flue gas in an
      MSWI was investigated by pilot-scale experiments using a bag filter (BF). The
      injection of AC increases the Hg reduction ratio by 20-30% compared with cases
      without AC injection. The Hg reduction ratio increases as the flue gas
      temperature decreases. The Hg reduction ratio is closely related to the inlet Hg
      concentration and was expressed with a Langmuir-type adsorption isotherm.

PMID- 12184693
TI  - Effect of NOx control processes on mercury speciation in utility flue gas.
AB  - The speciation of Hg in coal-fired flue gas can be important in determining the
      ultimate Hg emissions as well as potential control options for the utility. The
      effects of NOx control processes, such as selective catalytic reduction (SCR) and
      selective non-catalytic reduction (SNCR), on Hg speciation are not well
      understood but may impact emissions of Hg. EPRI has investigated the reactions of
      Hg in flue gas at conditions expected for some NOx control processes. This paper
      describes the methodology used to investigate these reactions in actual flue gas
      at several power plants. Results have indicated that some commercial SCR
      catalysts are capable of oxidizing elemental Hg in flue gas obtained from the
      inlets of SCR or air heater units. Results are affected by various flue gas and
      operating parameters. The effect of flue gas composition, including the presence
      of NH3, has been evaluated. The influence of NH3 on fly ash Hg reactions also is
      being investigated.

PMID- 12184694
TI  - Facing crackdown, dietary supplement companies promise changes.

PMID- 12184695
TI  - Confused by results of study on use of fecal panel for dogs.

PMID- 12184696
TI  - What is your diagnosis? Large gas-distended stomach with intestines displaced
      caudally.

PMID- 12184697
TI  - Animal sources of salmonellosis in humans.

PMID- 12184698
TI  - Evaluation of trends in frequency of urethrostomy for treatment of urethral
      obstruction in cats.
AB  - OBJECTIVE: To determine hospital proportional morbidity rates (HPMR) for urethral
      obstructions, urethral plugs or urethroliths, and urethrostomies in cats in
      veterinary teaching hospitals (VTH) in Canada and the United States between 1980
      and 1999. DESIGN: Epidemiologic study. ANIMALS: 305,672 cats evaluated at VTH.
      PROCEDURES: Yearly HPMR were determined for cats with urethral obstructions,
      urethral plugs or urethroliths, or urethrostomies from data compiled by the
      Purdue Veterinary Medical Database. The test for a linear trend in proportions
      was used. RESULTS: Urethral obstructions were reported in 4,683 cats. Yearly HPMR
      for urethral obstructions declined from 19 cases/1,000 feline evaluations in 1980
      to 7 cases/1,000 feline evaluations in 1999. Urethral plugs or urethroliths
      affected 1,460 cats. Yearly HPMR for urethral plugs or urethroliths decreased
      from 10 cases/1,000 feline evaluations in 1980 to 2 cases/1,000 feline
      evaluations in 1999. A total of 2,359 urethrostomies were performed. Yearly HPMR
      for urethrostomies decreased from 13 cases/1,000 feline evaluations in 1980 to 4
      cases/1,000 feline evaluations in 1999. CONCLUSIONS AND CLINICAL RELEVANCE:
      Frequency of feline urethrostomies performed at VTH in Canada and the United
      States declined during the past 20 years and paralleled a similar decline in
      frequency of urethral obstructions and urethral plugs or urethroliths. These
      trends coincide with widespread use of diets to minimize struvite crystalluria in
      cats, which is important because struvite has consistently been the predominant
      mineral in feline urethral plugs during this period.

PMID- 12184699
TI  - Evaluation of sedative and cardiorespiratory effects of romifidine and romifidine
      butorphanol in cats.
AB  - OBJECTIVE: To determine sedative and cardiorespiratory effects of romifidine
      alone and romifidine in combination with butorphanol and effects of preemptive
      atropine administration in cats sedated with romifidine-butorphanol. DESIGN:
      Randomized crossover study. ANIMALS: 6 healthy adult cats. PROCEDURES: Cats were
      given saline (0.9% NaCl) solution followed by romifidine alone (100 microg/kg
      [45.4 microg/lb], i.m.), saline solution followed by a combination of romifidine
      (40 microg/kg [18.1 microg/lb], i.m.) and butorphanol (0.2 mg/kg [0.09 mg/lb],
      i.m.), or atropine (0.04 mg/kg [0.02 mg/lb], s.c.) followed by romifidine (40
      microg/kg, i.m.) and butorphanol (0.2 mg/kg, i.m.). Treatments were administered
      in random order, with > or = 1 week between treatments. Physiologic variables
      were determined before and after drug administration. Time to recumbency,
      duration of recumbency, time to recover from sedation, and subjective evaluation
      of sedation, muscle relaxation, and analgesia were assessed. RESULTS: Bradycardia
      developed in all cats that received saline solution and romifidine-butorphanol or
      romifidine alone. Preemptive administration of atropine prevented bradycardia for
      50 minutes in cats given romifidine-butorphanol. Oxyhemoglobin saturation was
      significantly decreased 10 minutes after romifidine-butorphanol administration in
      atropine-treated cats. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggested that
      administration of romifidine alone or romifidine-butorphanol causes a significant
      decrease in heart rate and that preemptive administration of atropine in cats
      sedated with romifidine-butorphanol effectively prevents bradycardia for 50
      minutes.

PMID- 12184700
TI  - Cross-sectional study of serum antibodies against Sarcocystis neurona in cats
      tested for antibodies against Toxoplasma gondii.
AB  - OBJECTIVE: To determine apparent seroprevalence of antibodies against Sarcocystis
      neurona in a population of domestic cats previously tested for antibodies against
      Toxoplasma gondii. DESIGN: Cross-sectional study. SAMPLE POPULATION: Serum from
      196 domestic cats. PROCEDURE: Banked serum samples submitted to the Michigan
      State University Animal Health Diagnostic Laboratory for T. gondii diagnostic
      testing were tested for antibodies against S. neurona by use of an indirect
      fluorescent antibody (IFA) test and a western blot test. Submission records were
      analyzed to determine descriptive statistics and test for associations between
      positive results of a test for S. neurona and other variables in the data set.
      RESULTS: 10 of 196 (5%) samples yielded positive results for antibodies against
      S. neurona by use of western blot analysis, whereas 27 samples yielded positive
      results by use of the IFA. No association was found between S. neurona western
      blot test results and T. gondii test results, age, sex, or the reason for T.
      gondii testing. The S. neurona IFA titer was positively and significantly
      associated with positive results of western blot analysis. CONCLUSIONS AND
      CLINICAL RELEVANCE: Domestic cats are not likely to play a substantial role as
      intermediate hosts in the natural life cycle of S. neurona. Results indicate that
      natural infection of domestic cats may occur, and small animal practitioners
      should be aware of this fact when evaluating cats with neurologic disease. The S.
      neurona IFA test had lower specificity than western blot analysis.

PMID- 12184701
TI  - Evaluation of antithyroglobulin antibodies after routine vaccination in pet and
      research dogs.
AB  - OBJECTIVE: To determine whether routine vaccination induces antibodies against
      bovine thyroglobulin and autoantibodies against canine thyroglobulin in dogs.
      DESIGN: Prospective study. ANIMALS: 20 healthy research Beagles and 16 healthy
      pet dogs. PROCEDURE: For the research Beagles, 5 dogs were vaccinated with a
      multivalent vaccine and a rabies vaccine, 5 dogs received only the multivalent
      vaccine, 5 dogs received only the rabies vaccine, and 5 dogs were unvaccinated
      controls. The multivalent vaccine was administered at 8, 10, 12, 16, 20, 26, and
      52 weeks of age and every 6 months thereafter. The rabies vaccine was
      administered at 16 and 52 weeks of age and then once per year. Blood was
      collected from all dogs at 8, 16, and 26 weeks of age and then 4 times yearly.
      Assays for antibodies directed against bovine and canine thyroglobulin were
      performed prior to and 2 weeks after each yearly vaccination. For the pet dogs,
      blood was collected prior to and 2 weeks after 1 vaccination. RESULTS: In the
      research Beagles, there was a significant increase in anti-bovine thyroglobulin
      antibodies in all vaccinated dogs, compared with control dogs. There was a
      significant increase in anti-canine thyroglobulin antibodies in the 2 groups of
      dogs that received the rabies vaccine but not in the group that received the
      multivalent vaccine alone. In the pet dogs, there was a significant increase in
      anti-canine thyroglobulin antibodies after vaccination but no significant change
      in anti-bovine thyroglobulin antibodies. CONCLUSIONS AND CLINICAL RELEVANCE:
      Recent vaccination may result in increased anti-canine thyroglobulin antibodies.
      Whether these antibodies have a deleterious effect on canine thyroid function is
      unknown.

PMID- 12184702
TI  - Comparison of the effects of four antiarrhythmic treatments for familial
      ventricular arrhythmias in Boxers.
AB  - OBJECTIVE: To evaluate the effect of 4 antiarrhythmic treatment protocols on
      number of ventricular premature complexes (VPC), severity of arrhythmia, heart
      rate (HR), and number of syncopal episodes in Boxers with ventricular
      tachyarrhythmias. DESIGN: Randomized controlled clinical trial. ANIMALS: 49
      Boxers. PROCEDURE: Dogs with > 500 VPC/24 h via 24-hour ambulatory ECG (AECG)
      were treated with atenolol (n = 11), procainamide (11), sotalol (16), or
      mexiletine and atenolol (11) for 21 to 28 days. Results of pre- and posttreatment
      AECG were compared with regard to number of VPC/24 h; maximum, mean, and minimum
      HR; severity of arrhythmia; and occurrence of syncope. RESULTS: Significant
      differences between pre- and posttreatment number of VPC, severity of arrhythmia,
      HR variables, or occurrence of syncope were not observed in dogs treated with
      atenolol or procainamide. Significant reductions in number of VPC, severity of
      arrythmia, and maximum and mean HR were observed in dogs treated with mexiletine
      atenolol or sotalol; occurrence of syncope was not significantly different
      between these 2 treatment groups. CONCLUSIONS AND CLINICAL RELEVANCE: Treatment
      with sotalol or mexiletine-atenolol was well tolerated and efficacious. Treatment
      with procainamide or atenolol was not effective.

PMID- 12184703
TI  - Infection with Basidiobolus ranarum in two dogs.
AB  - Basidiobolus ranarum is a saprophytic fungus in the environment that also is a
      part of the endogenous microflora in the gastrointestinal tract of several
      vertebrates. These organisms may penetrate skin or muscosa of humans and other
      animals, causing granulomatous inflammation. Two dogs infected with B. ranarum
      had prolonged or repeated exposure to water or soil in their environment. One dog
      had progressive subcutaneous infection of all the limbs, and the other dog had
      recurrent coughing and dyspnea caused by tracheobronchitis. In both dogs,
      secondary bacterial infection of the lesions was evident. Treatment of the dog
      with subcutaneous infection involved cutaneous dressings and sequential use of
      enrofloxacin and itraconazole; however, this resulted in suspected liver damage
      without clinical improvement. Subsequent treatment with potassium iodide and a
      lipid formulation of amphotericin B was also unsuccessful, and the dog was
      euthanatized. The other dog was treated alternately with enrofloxacin and
      itraconazole. When the clinical signs and infection returned, combination
      treatment with both drugs was more effective; however, the dog developed liver
      damage. Subsequent treatment with enrofloxacin on an intermittent basis
      controlled the dog's coughing during a 3-year period.

PMID- 12184704
TI  - Mineralized paraprostatic cyst as a potential contributing factor in the
      development of perineal hernias in a dog.
AB  - Perineal hernias almost exclusively affect male dogs (sexually intact or
      castrated). Factors that may contribute or predispose a dog to perineal hernias
      include tenesmus, pelvic musculature variations (male vs female), and gonadal
      hormone influence. In dogs with perineal hernias and tenesmus it is important to
      include rectal and prostatic diseases, including paraprostatic cysts, in the
      differential list of potential underlying causes. Surgical correction of the
      perineal hernia with a perineal herniorrhaphy is indicated. Successful treatment
      depends on the degree of preexisting neurologic alterations, meticulous surgical
      technique, and identification and correction of underlying contributing factors.
      Paraprostatic cysts develop predominantly in sexually intact medium to large
      breed dogs. These cysts are thin-walled structures often attached to the
      prostatic dorsal midline. Osseous metaplasia of paraprostatic cysts may occur.
      Clinical signs of tenesmus often result from compression on adjacent structures
      (urinary bladder and colon), and tenesmus may contribute to the development of
      perineal hernias. Preferred treatment of a paraprostatic cyst is surgical removal
      and castration. This report describes a dog with bilateral perineal hernias and a
      large mineralized paraprostatic cyst that was identified as a possible
      contributing factor to the hernias.

PMID- 12184705
TI  - Effect of hemi-circumferential periosteal transection and elevation in foals with
      experimentally induced angular limb deformities.
AB  - OBJECTIVE: To evaluate the effect of hemi-circumferential periosteal transection
      and elevation (HCPTE) in foals with, experimentally induced angular limb
      deformities. DESIGN: Prospective study. ANIMALS: 10 healthy foals. PROCEDURE:
      When foals were 30 days old, transphyseal bridge implants were placed on the
      lateral aspects of both distal radial physes. At 90 days of age (or when 15
      degrees of angulation had developed), implants were removed, and HCPTE was
      performed on 1 limb. Foals were confined in small pens after surgery; the front
      feet of the foals were rasped weekly to maintain medial-to-lateral hoof wall
      balance. Dorsopalmar radiographic projections of the carpi were obtained before
      HCPTE and 2, 4, 6, 8, and 48 weeks later. RESULTS: At the time of transphyseal
      bridge removal and HCPTE, both treated and control limbs were observed to have a
      significantly greater carpal valgus, compared with the initial degree of
      angulation at 30 days of age. Following HCPTE or sham surgery, all limbs
      straightened over the subsequent 2 months of the study. Median angulation was not
      significantly different between treated and control limbs at any time during the
      study. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggest that in foals with
      experimentally induced limb deformities, HCPTE was no more effective than stall
      confinement and hoof trimming alone for correction of the deformity.

PMID- 12184706
TI  - Jejunoileal anastomosis following small intestinal resection in horses: seven
      cases (1999-2001).
AB  - OBJECTIVE: To report the postoperative outcome in horses undergoing jejunoileal
      anastomosis performed with a 2-layer simple continuous technique. DESIGN:
      Retrospective study. ANIMALS: 7 horses. PROCEDURE: Information regarding
      signalment, clinical signs, findings at surgery, and postoperative complications
      was obtained from medical records of horses that underwent exploratory ventral
      midline celiotomy, small intestinal resection, and jejunoileal anastomosis to
      correct various small intestinal strangulating lesions. Follow-up information was
      obtained via telephone conversations with owners or trainers. RESULTS: Six males
      and 1 female of various breeds aged 10 months to 27 years and weighing 312 to 785
      kg (686.4 to 1,727 lb) were included. The most common complications were mild to
      moderate tachycardia and mild to moderate signs of abdominal pain. Two horses
      developed incisional infections and soft, fluctuant swelling at the incision site
      following resolution of the infection. Follow-up time ranged from 7 to 17 months
      after surgery. Owners reported no further colic episodes and no diet change
      necessary following surgery. All horses had returned to their intended level of
      use. CONCLUSIONS AND CLINICAL RELEVANCE: Advantages to the jejunoileal technique
      include maintaining the normal ileocecal valve and a postoperative recovery
      period similar to that described following other small intestinal anastomoses.
      Jejunoileal anastomosis is a viable alternative to ileal bypass. This technique
      appears to result in a postoperative complication rate similar to that reported
      following jejunojejunostomy procedures.

PMID- 12184707
TI  - Percutaneous tube cystostomy and vesicular irrigation for treatment of
      obstructive urolithiasis in a goat.
AB  - Treatment of a 3-month-old male goat with obstructive urolithiasis by means of
      percutaneous tube cystostomy and vesicular irrigation with a chemolysis solution
      is described. The cystostomy tube was inserted percutaneously with
      ultrasonographic guidance. Patency of the urethra was reestablished with no
      clinical evidence of urethral stricture or recurrence of obstruction during the
      following 12 months. Results in this goat suggest that percutaneous tube
      cystostomy may be an economical alternative to surgical cystostomy tube
      placement. Chemical dissolution of calcium phosphate uroliths with a commercially
      available compound appears to be feasible in goats.

PMID- 12184708
TI  - Help-seeking and associated factors in female urinary incontinence. The Norwegian
      EPINCONT Study. Epidemiology of Incontinence in the County of Nord-Trondelag.
AB  - OBJECTIVES: To assess the proportion of women who visit their doctor because of
      urinary incontinence and investigate factors associated with help-seeking.
      DESIGN: Postal invitation, questionnaire covering many health topics including
      urinary incontinence, received at a screening station. SETTING: The Norwegian
      EPINCONT Study is part of a large cross-sectional population-based survey
      performed in the county of Nord-Trondelag during the period 1995-97. SUBJECTS:
      6625 women (out of 27,936 participating women), 20 years or older, categorised as
      incontinent according to their answers to the questionnaire. RESULTS: 26% of the
      incontinent women had seen a doctor for their incontinence. Increasing age,
      impact, severity and duration were all significantly associated with consultation
      rate, as were urge and mixed types compared with stress incontinence, and having
      visited any doctor during the previous 12 months. Fifty percent of the women with
      significant incontinence (moderate/severe incontinence perceived as troublesome)
      had seen a doctor because of their incontinence. CONCLUSIONS: Only a fourth of
      the women with any incontinence, and half of the women with significant
      incontinence had consulted a doctor. Older age and high impact of the symptoms
      were the factors most strongly associated with help-seeking.

PMID- 12184709
TI  - Medical consequences of violence: a two-year prospective study from a primary
      care accident and emergency department in Norway.
AB  - OBJECTIVE: To assess the medical consequences of violence from the perspective of
      a primary care accident and emergency department. DESIGN: Prospective
      observational study. SETTING: Bergen Legevakt (AED). SUBJECTS: All assault
      victims treated at the AED 1994-96. MAIN OUTCOME MEASURES: Diagnoses, treatments,
      number of consultations at the AED, sickness certificates, rates of admittances
      to hospitals, referrals to specialists and injury severity ratings using
      Abbreviated Injury Scale (AIS) and Shepherd's injury severity scale. RESULTS:
      1803 assault victims were registered, 433 (24%) females and 1370 (76%) males.
      Most injuries were of slight severity, corresponding to AIS 0 to 1 (82%) or
      Shepherd's scale 0 to 1 (74%). Bruises/contusions and cuts/lacerations dominated.
      The majority of patients did not receive any specific treatment at the AED and
      they were not given sickness certificates, but 11% were admitted to hospitals and
      30% were referred to specialists. Males were more likely to be seriously injured
      than females. CONCLUSION: Most physical injuries caused by violence and treated
      at a primary care accident and emergency department are minor.

PMID- 12184710
TI  - The added value of the registration of home accidents in general practice.
AB  - OBJECTIVES: To determine the number, the nature and the circumstances of home
      accidents managed in general practices, and to compare the results with the
      European Home and Leisure Accidents Surveillance System (EHLASS) data. DESIGN: A
      prospective population survey of all domestic accidents managed in 138 sentinel
      general practices during 1995/96. SETTING: Primary health care. SUBJECTS: In
      total, 4481 patients were included, of which 58% were female. MAIN OUTCOME
      MEASURES: The incidence of domestic accidents managed in general practices; the
      nature and place of the accident; the nature of the injury; the predisposing
      factors and related products. RESULTS: The highest incidence of home accidents
      was measured among children and the elderly. The median age was significantly
      lower for men (36 years) than for women (54 years). Among women, 74% of all home
      accidents were the result of a fall. The lesion is often a contusion or wound.
      Fractures were recorded in 20% of all home accidents. Three-quarters of all
      fractures involved women, especially older women. Most accidents among women
      (80%) occurred during motion and housework. Among men, 65% of all home injuries
      occurred during motion and do-it-yourself jobs. CONCLUSION: Because of the close
      relation with most patients and a knowledge of their living conditions, the GP is
      able to provide more reliable information on the circumstances of accidents than
      are health care providers in hospitals. The prevention of home accidents should
      at least partly be based on the results provided by general practitioners.

PMID- 12184712
TI  - Personal health care and the new media in anticoagulant treatment.
AB  - OBJECTIVE: To determine the feasibility of a more personal anticoagulant
      treatment follow-up routine involving the use of a personal measurement device
      along with the new media (e.g. the Internet). DESIGN: A telephone interview.
      SETTING: The municipality of Ikaalinen with a total population of 7795. SUBJECTS:
      Forty patients on anticoagulant treatment who have personal responsibility for
      their treatment follow-up. MAIN OUTCOME MEASURES: Demographic data, data and
      opinions on anticoagulant treatment and data and opinions on personal health care
      and the new media. RESULTS: More than two-thirds of the interviewed were
      generally pleased with the current AC treatment routine in the Ikaalinen area.
      Sixty-eight percent of the patients feel that they are able to determine the
      anticoagulant dosage from the follow-up test results and almost a third have
      independently changed their dosage. Approximately half of the interviewed were
      willing to take various health-related measurements at home, but approximately
      only 20% of the interviewed were ready to use health-related services; for
      example, related to the follow-up of anticoagulant treatment, through the new
      media. CONCLUSION: Part of the population receiving anticoagulant treatment is
      ready to move to a more personal treatment routine involving home measurements in
      follow-up tests. However, most interviewed patients were not interested in using
      the new media as part of the new routine.

PMID- 12184711
TI  - Incidence and costs of falls and fall injuries among elderly in institutional
      care.
AB  - OBJECTIVE: To investigate the incidence and costs of falls among the elderly in
      institutional care. DESIGN: A prospective study during the course of 1 year.
      SETTING: Four institutions in Finland. SUBJECTS: A total of 554 falls and 211
      fall injuries among patients over 60 years of age. MAIN OUTCOME MEASURES: Falls
      and fall injuries were recorded prospectively. Treatment and the costs of
      injuries were analysed retrospectively. The incidence of falls and fall injuries
      was expressed per 1000 person years. Costs of fall injuries treated outside the
      patient's own ward were calculated. RESULTS: The total incidence of falls was
      1398/1000 person years. The incidence of fractures per 1000 person years was 54
      (95% CI; 25-83) in women and 10 (95% CI; 1-54) in men. Women fell on their hips
      or buttocks more often than men did (p < 0.01). Incidence of head injuries per
      1000 person years was 214 (95% CI; 160-267) in women and 433 (95% CI; 302-565) in
      men. The average costs were Euro 944 per fall. CONCLUSION: One-third of all falls
      resulted in an injury and every fifth injurious fall resulted in treatment
      outside the patient's own ward. The type of fall and the injury profile differed
      between men and women.

PMID- 12184714
TI  - How to safeguard the right of common access in the health service.

PMID- 12184713
TI  - Influence of two different inhalation devices on therapy compliance in asthmatic
      patients.
AB  - OBJECTIVE: To examine the influence of inhalation device (Autohaler versus
      metered dose inhaler) and patients' subjective opinion towards the different
      devices, as well as daily frequency and duration of treatment on medication
      compliance. DESIGN: Prospective study measuring compliance in the same patients
      of the Autohaler twice daily with the metered dose inhaler twice daily, as well
      the Autohaler twice daily with the Autohaler four times daily. SETTING: Primary
      health care. SUBJECTS: 34 subjects with asthma. MAIN OUTCOME MEASURES: Patients
      preference and compliance. RESULTS: Patients preferred the Autohaler. The
      percentage of patients with a negative opinion towards the metered dose inhaler
      was 38% compared with 12% towards the Autohaler. The median values of the
      compliance rate of the Autohaler with twice and four times daily frequency were
      90.8% (25-75th percentile 61.6-98.0%) and 78.5% (25-75th percentile 49.0%-91.2%),
      respectively (p < 0.001). The duration of treatment period had a significant
      negative influence on compliance when four times daily dosage frequency was
      prescribed (p = 0.05). CONCLUSION: In conclusion, the devices (metered dose
      inhaler and Autohaler) and the patients' opinion about the devices did not
      significantly contribute to the compliance rates. Compliance towards the
      medication treatment, however, is negatively influenced by a high daily
      frequency.

PMID- 12184716
TI  - Unfavourable working conditions for female GPs. A comparison between Swedish
      general practitioners and district nurses.
AB  - OBJECTIVE: The aim was to analyse gender and occupational differences in the
      psychosocial working conditions of general practitioners (GPs) and district
      nurses (DNs) in Sweden. DESIGN: A stratified random sample of GPs (n = 566) and
      DNs (n = 554) from four county councils in Sweden. The overall participation rate
      was 83%. SETTING: Primary health care. MAIN OUTCOME MEASURES: A mailed
      questionnaire comprising 10 items providing demographic data and 36 items on
      psychosocial working conditions was used. The questionnaire had been tested for
      validity and reliability. A factor analysis included five items: strains and
      symptoms, professional content, social support at work, workload and job control.
      RESULTS: Professional content was the most positively rated aspect, whereas
      workload was the most negatively rated. GPs perceived a higher workload and lower
      social support than did the DNs. Female GPs scored significantly more negatively
      than both male GPs and female DNs did in four out of the five factors. Female GPs
      reported a high workload, low job control and low social support at work. Female
      DNs, too, reported a high workload, relatively low job control but fairly strong
      social support. CONCLUSION: Female GPs perceived more unfavourable psychosocial
      working conditions than both male GPs and female DNs did in the same
      organisational setting.

PMID- 12184715
TI  - Methodological problems in comparing audits from the Nordic countries. A critical
      review of results from audit on Nordic general practitioners' management of
      patients with psychiatric problems.
AB  - In 1998, an audit on psychiatric problems in general practice was conducted in
      four Nordic countries. Five-hundred-and-sixty general practitioners participated
      and made registration according to the Audit Project Odense method. This paper
      describes the methodological problems related to international differences in the
      organisation of health care, recruitment of general practitioners and the
      registration of contacts. Nordic differences in this audit gave rise to inspiring
      discussions at national meetings, but methodological problems remain to be
      resolved if the results are to prove useful in scientific reporting.

PMID- 12184717
TI  - Gender bias in female physician assessments. Women considered better suited for
      qualitative research.
AB  - OBJECTIVE: To analyse whether physician assessment of scientific quality is
      biased by gender. DESIGN: Two fictive research abstracts on back pain treatment
      were constructed, one with a quantitative and one with a qualitative design.
      Authorship was assigned to either a woman or a man. SUBJECTS: 1637 randomly
      selected Swedish physicians were asked to judge the scientific quality of the two
      designs in a structured assessment form. MAIN OUTCOME MEASURES: The assessments
      of 1364 abstracts (286 female and 394 male assessors) were analysed by chi-square
      test and logistic regression. RESULTS: The quantitative design was judged the
      same, regardless of the gender of the author or assessor. The qualitative design,
      however, was ranked as more accurate, trustworthy, relevant and interesting with
      a female author. Women assessors upgraded female authors more than male authors,
      while male assessors reflected no gender differences. Assessor speciality
      interacted with judgement; physicians in primary care appreciated the qualitative
      abstract more than hospital physicians did (OR 2.78; 95% CI 1.97-3.92).
      CONCLUSION: Gender seems to affect scientific evaluations. The results are worth
      considering in situations where research is judged and interpreted, in medical
      tutoring, research guidance, peer reviewing and certainly in forming evaluation
      committees for research funding.

PMID- 12184718
TI  - Health problems among UN refugees at a family medical centre in Ankara, Turkey.
AB  - OBJECTIVES: Political lability in the Near East has brought about the migration
      of refugees from adjacent countries to Turkey in recent years. To provide an
      effective health service for refugees, a needs assessment has to be done. UN
      refugees referring to a family medical centre located in Ankara, Turkey, were
      therefore investigated for health problems. DESIGN: Medical records were studied
      retrospectively for age distribution, gender, origin, diagnoses, type of
      treatment and referral to a secondary health care setting. SUBJECTS: 212 refugees
      of different countries (mostly from Iraq, Iran and Palestine). RESULTS:
      Infectious disease was the most often diagnosed condition. Post-traumatic stress
      disorders could be observed in 12% of refugees. CONCLUSION: The family physician
      must be careful not to misdiagnose these disorders during medical examination.
      Most disease can be diagnosed and treated in family practice. Special care must
      be taken in the case of mental disorders.

PMID- 12184719
TI  - Respect for patients' dignity in primary health care: a critical appraisal.
AB  - OBJECTIVE: To address the challenges of modern health care that patients call
      "inhumane medicine" by investigating the concept of dignity. That is, to answer
      the question: what does it mean to respect patients' dignity, and can focusing
      attention on dignity address the lack of trust in and respect for GPs? DESIGN: To
      scrutinise the concept of dignity as a basic term in health care by analysing its
      limitations. IMPLICATIONS: Respecting patients' dignity, and meeting them as
      whole persons and not as the aggregation of organs, functions and processes, is
      crucial in modern health care. However, even a health care focusing on dignity
      can become paternalistic and undignified. Hence, dignity appears to be a concept
      that addresses a basic challenge in modern health care, but which can be
      dangerous if its limitations are not respected.

PMID- 12184720
TI  - Are adolescents with frequent pain symptoms more depressed?
AB  - OBJECTIVE: To study predicting value of pain symptoms in detecting depression
      among adolescents. DESIGN: A population-based classroom survey of 14-16-year-old
      adolescents. SETTING: Secondary schools in two regions of Finland (Vaasa and
      Pirkanmaa). SUBJECTS: Every secondary school in these two regions was asked to
      participate in the study. The final sample comprised 17,643 adolescents in 8th
      and 9th grades (mean age 15.3 years). MAIN OUTCOME MEASURES: The subjects were
      asked to rate the frequency of headache, stomach-ache, low back pain and neck or
      shoulder pain. Depression was measured using the Finnish modification of the
      short Beck Depression Inventory (R-BDI). Trait anxiety was questioned in an item
      formulated analogously to R-BDI questions. RESULTS: Prevalence of depression was
      higher among adolescents with recurrent pain symptoms. Each of the four measured
      pain symptoms predicted depression independently and accumulation of different
      pain symptoms increased the odd ratios for depression. Anxiety did not change the
      association between pain symptoms and depression. CONCLUSION: Recurrent pain
      symptoms are associated with depression among adolescents. Clinicians working
      with adolescents should be aware of this association and interview adolescents
      with recurrent pains for possible underlying depression.

PMID- 12184721
TI  - Treatment failures after antibiotic therapy of uncomplicated urinary tract
      infections. A prescription database study.
AB  - OBJECTIVES: The efficacy of sulfamethizole and pivmecillinam in the treatment of
      urinary tract infections (UTI) has been questioned because of an increase in the
      prevalence of resistant strains. The aim of this study was to describe the risk
      of treatment failures over the last 10 years. DESIGN: Retrospective cohort study.
      MATERIAL: Data were retrieved from Odense Pharmaco Epidemiological Database and
      consisted of women receiving sulfamethizole (n = 44,716) or pivmecillinam (n =
      3093) during the period 1990-99. MAIN OUTCOME MEASURES: Prescription of a new
      antibiotic drug appropriate for UTI within 4 weeks after the initial treatment
      was considered as an indicator for a treatment failure. The risk of treatment
      failure was estimated by calculating the cumulative incidence proportion of new
      antibiotic prescriptions within 4 weeks after the initial treatment. RESULTS: A
      new antibiotic followed 8% of sulfamethizole and 9.5% of pivmecillinam
      treatments. The cumulative incidence proportion of treatment failures did not
      change during the study period. A logistic regression model showed pivmecillinam
      to be associated with a higher risk of treatment failure (OR 1.42, CI 1.14-1.77)
      than sulfamethizole. CONCLUSION: This study does not support a change in current
      Danish practice of sulfamethizole being first-line treatment for uncomplicated
      UVI.

PMID- 12184722
TI  - Isolation and distribution of endomorphins in the central nervous system.
AB  - Endomorphin-1 (Tyr-Pro-Trp-Phe-NH2, EM-1) and endomorphin-2 (Tyr-Pro-Phe-Phe-NH2,
      EM-2) have the highest affinity and selectivity for the mu-opioid receptor (MOP
      R) of all known mammalian opioids. They were isolated from bovine and human
      brain, and are structurally distinct from the other endogenous opioids. Both EM-1
      and EM-2 have potent antinociceptive activity in a variety of animal models of
      acute, neuropathic and allodynic pain. They regulate cellular signaling processes
      in a manner consistent with MOP-R-mediated effects. The EMs are implicated in the
      natural modulation of pain by extensive data localizing EM-like immunoreactivity
      (EM-LI) near MOP-Rs in several regions of the nervous system known to regulate
      pain. These include the primary afferents and their terminals in the spinal cord
      dorsal horn, where EM-2 is well-positioned to modulate pain in its earliest
      stages of perception. In a nerve-injury model of chronic pain, a loss of spinal
      EM2-LI occurs concomitant with the onset of chronic pain. The distribution of the
      EMs in other areas of the nervous system is consistent with a role in the
      modulation of diverse functions, including autonomic, neuroendocrine and reward
      functions as well as modulation of responses to pain and stress. Unlike several
      other mu opioids, the threshold dose of EM-1 for analgesia is well below that for
      respiratory depression. In addition, rewarding effects of EM-1 can be separated
      from analgesic effects. These results indicate a favorable therapeutic profile of
      EM-1 relative to other mu opioids. Thus, the pharmacology and distribution of EMs
      provide new avenues both for therapeutic development and for understanding the
      neurobiology of opioids.

PMID- 12184723
TI  - Morphological studies of the endomorphinergic neurons in the central nervous
      system.
AB  - Endomorphins (EMs) are newly found endogenous opioid peptides. Both endomorphin-1
      (EM-1) and -2 (EM-2) are composed of four amino acids. Their high affinity and
      specificity for mu-opioid receptors have been confirmed by many physiological and
      pharmacological studies. In the present minireview, we discuss the distribution
      and localization of these peptides. While EM-2 is more prevalent in the spinal
      cord and lower brainstem, EM-1 is more widely and densely distributed throughout
      the brain than EM-2. We also discuss the possible coexistence of EM with other
      neurotransmitters. Finally, we introduce some new results regarding the
      ultrastructure and synaptic relationships of EM-2 obtained by the immunoelectron
      microscopic method.

PMID- 12184724
TI  - The antinociceptive properties of endomorphin-1 and endomorphin-2 in the mouse.
AB  - Two highly selective mu-opioid receptor agonists, endomorphin-1 (EM-1) and
      endomorphin-2 (EM-2), have been identified and postulated to be endogenous mu
      opioid receptor ligands. The present minireview describes the antinociceptive
      properties with the tail-flick test of these two ligands given
      intracerebroventricularly (i.c.v.) and intrathecally (i.t.) in ICR mice. EM-1 or
      EM-2 given i.c.v. or i.t. dose-dependently produce antinociception. These
      antinociceptive effects induced by EM-1 and EM-2 given i.c.v. or i.t. are
      selectively mediated by the stimulation of mu-, but not delta- or kappa-opioid
      receptors. Like other mu-opioid agonists morphine and DAMGO ([D-Ala2,NMePhe4,Gly5
      ol]enkephalin), EM-1 and EM-2 given i.c.v. activate descending pain controls by
      the releases of noradrenaline and 5-HT and subsequently act on alpha2
      adrenoceptors and 5-HT receptors, respectively, in the spinal cord to produce
      antinociception. However, the antinociception induced by EM-2 given i.c.v. or
      i.t. also contain an additional component, which is mediated by the release of
      dynorphin A(1-17) acting on kappa-opioid receptors at the supraspinal and spinal
      sites. In addition, the antinociception induced by EM-2 given i.c.v. contains
      another component, which is mediated by the release of Met-enkephalin acting on
      delta2-opioid receptors in the spinal cord. It is proposed that there are two
      subtypes of mu-opioid receptors,which are involved in EM-1- and EM-2-induced
      antinociception. One subtype of mu-opioid receptors is stimulated by EM-1, EM-2
      and other mu-opioid agonists morphine and DAMGO; and another subtype of mu-opioid
      is sorely stimulated by EM-2 and is involved in the releases of dynorphin A(1-17)
      and Met-enkephalin for the production of antinociception.

PMID- 12184725
TI  - Differential antinociceptive effects induced by intrathecally-administered
      endomorphin-1 and endomorphin-2 in mice.
AB  - Two highly selective mu-opioid receptor (MOP-R) agonists, endomorphin-1 (EM-1)
      and endomorphin-2 (EM-2), have been identified and postulated to be endogenous
      ligands for MOP-R. Experiments were designed to determine the involvement of
      subtypes of MOP-R on the antinociceptive effects of EM-1 or EM-2 using the paw
      withdrawal test. The intrathecal (i.t.) injection of EM-1 and EM-2 produced dose
      dependent antinociception in mice 1 min after the injection. Subcutaneous (s.c.)
      pretreatment with naloxonazine (NLZ), a selective MOP1-R antagonist, dose
      dependently antagonized the antinociceptive effect of EMs. The antinociceptive
      effect of EM-2 was more sensitive to NLZ than that of EM-1. The selective
      heroin/morphine-6beta-glucuronide antagonist 3-methoxynaltrexone (3-MNT) blocked
      EM-2-induced antinociception, but not EM-1-induced antinociception. The dose
      response curve of EM-2 was shifted threefold to the right by pretreatment with
      s.c. 3-MNT at a dosage of 0.25 mg/kg. EM-2-induced antinociception was attenuated
      by pretreatment with s.c. nor-binaltorphimine and naltrindole, whereas the effect
      of EM-1 was not affected. Moreover, the antinociceptive effect of EM-2 was
      attenuated by i.t. pretreatment with antisera against dynorphin A(1-17) or
      methionine-enkephalin. These results suggest that EM-2-induced antinociception
      may be mediated by the subtype of MOP-R, which is sensitive to NLZ and 3-MNT, and
      by subsequent release of dynorphin A(1-17) and methionine-enkephalin in the
      spinal cord.

PMID- 12184726
TI  - Endomorphin-induced motivational effect: differential mechanism of endomorphin-1
      and endomorphin-2.
AB  - The newly discovered endogenous mu-opioid receptor (MOP-R) ligands endomorphin-1
      (EM-1) and -2 (EM-2) exhibit the highest specificity and affinity for the MOP-R
      of any endogenous substance so far described in the mammalian nervous system.
      This review focuses on differential mechanism of the motivational effects induced
      by EM-1 and EM-2. In the [35S]GTPgammaS binding assay, either EM-1 or EM-2 causes
      a concentration-dependent G-protein activation in brain membrane of normal mice,
      whereas neither EM-1 nor EM-2 produces any activation of G-protein in membranes
      obtained from the MOP-R knockout mice. These results provide direct evidence at
      the molecular level that both EMs act on the MOP-R as the endogenous MOP-R
      agonists. Based on the conditioned place preference paradigm in mice, EM-1 given
      intracerebroventriculally produced a dose-related place preference. This effect
      was abolished by pretreatment with the MOP-R antagonist beta-funaltrexamine (FNA)
      but not the delta-opioid receptor (DOP-R) antagonist naltrindole and the kappa
      opioid receptor (KOP-R) antagonist nor-bialtorphimine (BNI). Unlike EM-1, EM-2
      exhibited a place aversion. The aversive effect was inhibited by not only beta
      FNA but also nor-BNI. Place aversion produced by EM-2 was also attenuated by
      pretreatment with an antiserum against an endogenous KOP-R ligand dynorphin A(1
      17). These findings indicate that EM-1 may produce its rewarding effect via MOP
      Rs. Furthermore, the aversive effect induced by EM-2 may be associated with the
      stimulation of the EM-1-insensitive MOP-R subtype and necessarily activate an
      endogenous KOPergic system in the mouse brain.

PMID- 12184727
TI  - Differential mechanism of G-protein activation induced by endogenous mu-opioid
      peptides, endomorphin and beta-endorphin.
AB  - It is well documented that the mu-opioid receptor (MOP-R) is expressed by neurons
      in several central nervous system regions. Its occupancy with agonist drugs
      modulate a variety of physiological processes including pain, reward, stress,
      immune responses, neuroendocrine functions, and cardiovascular control. Based on
      the receptor binding assay, endomorphin-1 and endomorphin-2 have the highest
      specificity and affinity for the MOP-R of any endogenous substance so far
      described in the mammalian nervous system. In contrast, beta-endorphin exhibits
      the strongest actions among endogenous opioid peptides mainly through the MOP-R;
      however, it also shows the distinct pharmacological actions. Recent cloning and
      expression studies have indicated that MOP-Rs are seven-transmembrane domain
      receptors whose actions are mediated through activation of heterotrimeric guanine
      nucleotide binding proteins (G-proteins). The activation of G-proteins by MOP-Rs
      can be measured by assessing agonist-induced stimulation of membrane binding of
      guanosine-5'-o-(3-[35S]thio)triphosphate ([35S]GTPgammaS). The subject of the
      present review is to focus on the differential mechanism underlying G-protein
      activation induced by these mu-opioid peptides using the [35S]GTPgammaS binding
      assay.

PMID- 12184728
TI  - An involvement of granulocyte medullasin in phenytoin-induced gingival overgrowth
      in rats.
AB  - To investigate the relationship between histological changes and distributions of
      medullasin, a neutrophil elastase-like serine proteinase, in phenytoin-induced
      gingival overgrowth, we established a rat model of gingival overgrowth. Thirty
      two, 20-day-old male Fischer 344 rats were fed a diet containing phenytoin and
      sacrificed at 1, 2, 4 and 8 weeks. Control rats (n = 40) were fed the same diet,
      but without the drug and killed at the same weeks as experimental rats (n = 32)
      and 0 week (n = 8). The mandible specimens were resected and sectioned bucco
      lingually between the first and second molars. A marked inflammatory-cell
      infiltration and elongated rete pegs were seen in the phenytoin-treated group.
      The extent of the overgrowth assessed by computer image analysis and the density
      of medullasin-positive cells by immunohistochemistry in the approximal gingiva
      showed a significant increase in the phenytoin-treated group compared to the
      control group. A marked infiltration of the positive cells in experimental rats
      was observed as early as 2 weeks when gingival overgrowth was not fully
      established. Medullasin-positive cells were mostly neutrophils and partly
      macrophage-like cells. These findings suggest that medullasin may be involved in
      mainly host defense and secondarily collagen metabolism in the phenytoin-induced
      rat model of gingival overgrowth.

PMID- 12184729
TI  - 5-HT-induced, 5-HT3 receptor-mediated, and ruthenium red- and capsaicin-sensitive
      positive chronotropic effects in the isolated guinea pig atrium.
AB  - We investigated the mechanisms of 5-HT-induced tachycardia, which we reported
      previously to be triggered by 5-HT3 receptor stimulation, in the isolated guinea
      pig atrium in comparison with that induced by isoproterenol and histamine. We
      found that 5-HT-induced tachycardia was completely inhibited by ruthenium red. 5
      HT-induced tachycardia was reduced in the capsaicin pre-treated atrium as well as
      in the presence of capsaicin. The effects of isoproterenol and histamine were not
      affected by ruthenium red or capsaicin treatment. Furthermore, 5-HT-induced
      tachycardia was found to be potentiated by thiorphan, an inhibitor of peptide
      degeneration. Calcitonin gene-related peptide (CGRP) (1-37), a full agonist of
      CGRP1-like receptors, was found to act selectively as a potent stimulator of
      chronotropic action. CGRP (8-37), an antagonist of CGRP1-type receptors,
      inhibited 5-HT-induced tachycardia as well as effects induced by CGRP (1-37). The
      observation that tetrodotoxin failed to affect 5-HT-induced tachycardia excluded
      the involvement of 5-hydroxytryptaminergic interneurons. Thus, we confirmed that
      the mechanism of 5-HT-induced tachycardia is distinct from that induced by
      isoproterenol and histamine. In conclusion, the activation of 5-HT3 receptors on
      the sensory nerve terminals brought about ruthenium red-sensitive Ca2+ influx and
      resulted in the release of CGRP from capsaicin-sensitive stores, and then CGRP
      stimulated CGRP1-like receptors to produce 5-HT-induced tachycardia.

PMID- 12184730
TI  - Botulinum neurotoxin A blocks cholinergic ganglionic neurotransmission in the dog
      heart.
AB  - There is no data about whether botulinum neurotoxin inhibits the parasympathetic
      ganglionic neurotransmission in the heart, although botulinum toxin as a clinical
      drug inhibits the release of acetylcholine at the neuromuscular junction.
      Therefore, we investigated whether botulinum toxin (type A) injected into the
      sinoatrial (SA) fat pad inhibits decreases in heart rate induced by stimulation
      of the preganglionic parasympathetic nerves in the heart of the anesthetized dog.
      Stimulation of the parasympathetic nerves in the SA fat pad (SAP stimulation)
      prolonged the atrial interval but not the atrioventricular (AV) interval, and
      cervical vagus nerve stimulation (CV stimulation) prolonged both atrial and AV
      intervals. After botulinum toxin (20 or 25 mouse units) was injected into the SA
      fat pad, it gradually inhibited the prolongation of the atrial interval evoked by
      SAP and CV stimulations but not the prolongation of the AV interval evoked by CV
      stimulation. Conditioning successive stimulation of the cervical vagus nerves
      accelerated the inhibition by botulinum toxin of the chronotropic response to CV
      stimulation. These results indicate that selective injection of botulinum toxin
      into the SA fat pad blocks bradycardia mediated by parasympathetic ganglionic
      activation in the dog heart.

PMID- 12184731
TI  - Curative effect of combined treatment with alendronate and 1 alpha-hydroxyvitamin
      D3 on bone loss by ovariectomy in aged rats.
AB  - We investigated the combined effects of alendronate and 1alpha-hydroxyvitamin D3
      (1alpha(OH)D3) on the bone mass and strength in aged ovariectomized rats and
      compared them with those of single treatments. Forty-week-old female rats
      underwent ovariectomy or sham operation, and after 15 weeks, ovariectomized rats
      were daily administered vehicle alone, alendronate (0.2 or 1.0 mg/kg,p.o.),
      1alpha(OH)D3 (0.02 microg/kg, p.o.), or the combinations of 0.2 or 1.0 mg/kg of
      alendronate and 1alpha(OH)D3. After 12 weeks, the groups receiving combined
      treatments had significantly increased bone density and mechanical strength of
      the 4th lumbar vertebral body and the midfemur compared to the vehicle-treated
      group, and the effects were almost equal to or slightly less than the addition of
      those of the respective single treatments. The increase in mechanical strength
      was proportional to that in bone mineral density, suggesting that the stimulatory
      effects of these treatments on bone strength are ascribable primarily to those on
      bone mass. Analyses of histology, computed tomography, and biochemical markers
      confirmed the strong effect of the combined treatment on trabecular bone in
      particular, which was associated with increased trabecular number and decreased
      bone turnover. We propose that the combination of daily alendronate and
      1alpha(OH)D3 is clinically promising as a curative treatment of established
      postmenopausal osteoporosis.

PMID- 12184732
TI  - Effects of Wu-chu-yu-tang and its component herbs on drug-metabolizing enzymes.
AB  - The compound herbal medicine Wu-chu-yu-tang is used for the treatment of migraine
      and vomiting accompanying a cold. To assess the interactions of herb and drug
      metabolism, effects of Wu-chu-yu-tang on hepatic and renal cytochrome P450 (CYP),
      UDP-glucuronosyl transferase (UGT) and glutathione S-transferase (GST) were
      studied in C57BL/6J mice. Treatment of mice with 5 g/kg per day Wu-chu-yu-tang
      for 3 days caused 2.5-fold and 2.9-fold increases of liver microsomal 7
      ethoxyresorufin O-deethylation (EROD) and 7-methoxyresorufin O-demethylation
      activities, respectively. However, CYP activities toward 7-ethoxycoumarin,
      benzphetamine, N-nitrosodimethylamine, erythromycin and nifedipine, and
      conjugation activities of UGT and GST were not affected. In kidney, Wu-chu-yu
      tang-treatment had no effects on Cyp, UGT and GST activities. Among the four
      component herbs of Wu-chu-yu-tang, only Evodiae Fructus (Wu-chu-yu) extract
      increased EROD activity and CYP1a2 protein level. In E. Fructus, rutaecarpine,
      evodiamine and dehydroevodiamine are the main active alkaloids. At the doses
      corresponding to their contents in Wu-chu-yu-tang, rutaecarpine-treatment
      increased hepatic EROD activity, whereas evodiamine and dehydroevodiamine had no
      effects. These results demonstrated that ingestion of Wu-chu-yu-tang elevated
      mouse hepatic Cyp1a2 activity and protein level. E. Fructus and rutaecarpine
      contributed at least in part to the CYP1a2 induction by Wu-chu-yu-tang. Patients
      should be cautioned about the drug interaction of Wu-chu-yu-tang and CYP1A2
      substrates.

PMID- 12184734
TI  - Effects of toluene exposure on signal transduction: toluene reduced the signaling
      via stimulation of human muscarinic acetylcholine receptor m2 subtypes in CHO
      cells.
AB  - The organic solvent toluene is used widely in industry and is toxic to the
      central nervous system (CNS). To clarify the mechanisms of CNS toxicity following
      toluene exposure, especially with respect to the G protein-coupling of receptors,
      we determined the effects of toluene on the activation of Gi by stimulating human
      muscarinic acetylcholine receptor m2 subtypes (hm2 receptors) expressed in
      Chinese hamster ovary (CHO) cells. We first examined whether toluene affects the
      inhibition of adenylyl cyclase by Gi. The attenuation of forskolin-stimulated
      cAMP formation by the stimulation of hm2 receptors was reduced in a medium
      containing toluene. Next, we determined the effects of toluene on carbamylcholine
      stimulated [35S]GTPgammaS binding using membrane fractions of CHO cell expressing
      hm2 receptors. Carbamylcholine-stimulated [35S]GTPgammaS binding activity was
      markedly reduced when assayed using reaction buffers containing toluene. However,
      carbamylcholine-stimulated [35S]GTPgammaS binding activity was essentially
      unchanged following pretreatment of the cells with a toluene-saturated medium
      prior to membrane isolation. Toluene pretreatment and the toluene itself did not
      alter the characteristics of the binding of carbamylcholine and [3H]N
      methylscopolamine to hm2 receptors. On the contrary of the effect of toluene for
      [35S]GTPgammaS binding, the effect of toluene for attenuation of forskolin
      stimulated cAMP formation by the stimulation of hm2 receptors was irreversible.
      These observations indicate that toluene acts as an inhibitor of the signal
      transduction via hm2 receptor stimulation in CHO cells, and at least two
      mechanisms exist in the inhibition mechanisms by toluene.

PMID- 12184733
TI  - Hypoglycemic agent YM440 ameliorates the impaired hepatic glycogenesis after
      glucose loading by increasing glycogen synthase activity in obese Zucker rats.
AB  - We studied the role of hepatic glycogenesis in glucose intolerance after glucose
      loading in obese Zucker rats and the effects of YM440 ((Z)-1,4-bis[4-[(3,5-dioxo
      1,2,4-oxadiazolidin-2-yl)methyl]phenoxy]but-2-ene) on it. Lean and obese Zucker
      rats were treated with YM440 (300 mg/kg) for 14 days and then fasted for 20 h.
      Thirty percent glucose (0.6 g/kg) or saline was administered intravenously
      followed by NaH14CO3. Gluconeogenesis was evaluated based on the incorporation of
      14C-bicarbonate into blood glucose and hepatic glycogen. Obese rats showed an
      increase in the incorporation of 14C into blood glucose of 2.5-fold compared to
      lean rats. The glucose loading decreased the 14C-blood glucose release by 18% in
      obese rats and 43% in lean rats at 45 min. Glucose loading increased the hepatic
      glycogen content and 14C incorporation into glycogen in lean but not obese rats.
      YM440 decreased levels of fasting plasma insulin and blood glucose and the
      hepatic glycogen content by 50% compared with values for untreated obese rats.
      After glucose loading, YM440 promoted the incorporation of 14C into glycogen and
      glycogen synthase activity, leading to an improvement in glucose tolerance. These
      results indicate that glucose intolerance in obese rats was associated with
      decreased hepatic glycogenesis and YM440 improved the intolerance by normalizing
      glycogen metabolism.

PMID- 12184735
TI  - Different effects of oral administration of synthetic trypsin inhibitor on the
      pancreas between cholecystokinin-A receptor gene knockout mice and wild type
      mice.
AB  - The synthetic trypsin inhibitor camostat has been used for the treatment of acute
      and chronic pancreatitis in Japan based on the evidences obtained from a rat
      experimental model. However, rats differ from other rodents and from humans in
      terms of lacking a gallbladder and no response of pancreatic bicarbonate
      secretion to cholecystokinin (CCK). In the present study, we determined whether
      oral administration of camostat showed a trophic effect in mice as observed in
      rats and whether the trophic effect, if substantial, was mediated via the CCK-A
      receptor, using CCK-A receptor gene targeting mice. The chow containing 0.1%
      camostat was fed to 8-month-old mice. Three- and seven-day treatments with
      camostat did not affect pancreatic wet weight in CCK-A receptor (+/-) mice. After
      14-day treatment, the ratio of pancreatic wet weight/body weight was
      significantly lower in CCK-A receptor (-/-) than (+/+) mice. The protein and
      chymotrypsin contents were lower and amylase content was higher in CCK-A receptor
      (-/-) mice, compared to (+/+) mice. No pathological findings were observed by
      histological examination. Camostat has a trophic effect on the pancreas in mice
      and this effect is mediated via the CCK-A receptor, but is less potent than in
      rats.

PMID- 12184736
TI  - Inhibitory effects of metals on ATP-induced current through P2X7 receptor in
      NG108-15 cells.
AB  - We investigated the effects of heavy metal ions on the ATP-induced nonselective
      cation current through P2X7 receptor (I(NS x P2X7)) in NG108-15 cells using the
      whole-cell patch-clamp technique. Cu2+ inhibited the I(NS x P2X7) most potently
      among the metal ions investigated. Other metals such as Ni2+, Cd2+, Zn2+ and Co2+
      also inhibited the I(NS x P2X7) in concentration-dependent manners. The order of
      potency was Cu2+ >> Ni2+ > Cd2+ > Zn2+ > Co2+ with IC50 values of 16 nM, 0.79
      microM, 1.2 microM, 3.0 microM and 4.6 microM, respectively. Fe3+ (10 and 100
      microM) and Mn2+ (10 microM) did not affect the INS P2X7. A high concentration of
      Mn2+ (100 microM) slightly inhibited the I(NS x P2X7). When the concentration
      response curve of ATP was obtained in the presence of 3 and 10 nM Cu2+, the
      maximal response but not the EC50 value appeared to be reduced, suggesting that
      the inhibition is not competitive. These results suggest that under physiological
      and toxicological conditions, metal ions, such as Cu2+, Ni2+, Cd2+, Zn2+ and
      Co2+, may modulate P2X7 receptor channels as inhibitors.

PMID- 12184737
TI  - Effects of anions on ATP-induced [Ca2+], increase in NG108-15 cells.
AB  - We investigated the effects of anions on different P2 receptors by measuring ATP
      induced increase in intracellular Ca2+ concentration ([Ca2+]i) in fura-2-loaded
      NG108-15 and PC12 cells. In NG108-15 cells, ATP at 100 microM and 1 mM induced a
      transient and a sustained [Ca2+]i increase, respectively. The former, but not the
      latter, was inhibited by U-73122, indicating that the former was via the P2Y2
      receptor and the latter via the P2X7 receptor. When external Cl- was replaced by
      other anions, the [Ca2+]i increase mediated by the P2Y2 receptor was not changed,
      but that mediated by the P2X7 receptor varied in the order of aspartate- >
      methanesulfonate > Cl- > Br > or = I-. In PC12 cells, transient [Ca2+]i increases
      mediated by the P2Y2 and P2X2 receptors were not affected by various anions.
      These results suggest that modulation by anions is unique to the P2X7 receptor
      and does not occur in P2Y2 and P2X2 receptors. This may be because the mechanism
      of ATP binding to the P2X7 receptor may be different than that to other P2
      receptors.

PMID- 12184739
TI  - Cardiovascular effects of orally administered HNS-32, an originally synthesized
      azulene-1-carboxamidine derivative, assessed in the in vivo rat model.
AB  - HNS-32, an azulene-1-carboxamidine derivative, is an originally synthesized
      antiarrhythmic compound. Its cardiovascular effects after oral administration (1
      10 mg/kg) were assessed using the pentobarbital-anesthetized in vivo rat model in
      comparison with those of verapamil (3 mg/kg, p.o.). Verapamil decreased the heart
      rate and mean blood pressure and prolonged the PR interval without changing the
      QRS width (n = 6). Similar results were observed for HNS-32 except that the QRS
      width was prolonged by the highest dose and the effects occurred slowly and
      lasted longer. These results suggest that HNS-32 is an orally active slowly
      acting calcium plus sodium channel blocker.

PMID- 12184738
TI  - 7-Hydroxy-N,N'-di-n-propyl-2-aminotetraline, a preferential dopamine D3 agonist,
      induces c-fos mRNA expression in the rat cerebellum.
AB  - The effects of a preferential dopamine D3 receptor agonist 7-hydroxy-N,N'-di-n
      propyl-2-aminotetralin (7-OH-DPAT) on c-fos mRNA expression in the rat cerebellum
      were studied by Northern blot analysis. 7-OH-DPAT (0.003-10 mg/kg, s.c.) markedly
      increased c-fos mRNA expression in the cerebellum, while its effects in the
      striatum, nucleus accumbens, and frontal cortex were negligible. The effect of 7
      OH-DPAT on cerebellar c-fos mRNA expression was dose-dependent and statistically
      significant at doses of 0.3 mg/kg or more. A preferential dopamine D2 agonist,
      bromocriptine (0.01-3 mg/kg, s.c.), failed to increase c-fos mRNA expression in
      the cerebellum. The effect of 7-OH-DPAT was blocked by two dopamine D2-type
      receptor antagonists, haloperidol and perospirone, but not the D1-type-receptor
      antagonist SCH23390. Furthermore, dopaminergic denervation by 6-hydroxydopamine
      did not inhibit but rather potentiated the 7-OH-DPAT-induced c-fos mRNA
      expression in the cerebellum. These findings suggest that 7-OH-DPAT increases c
      fos mRNA expression in the rat cerebellum, probably through postsynaptic dopamine
      D3 receptor activation.

PMID- 12184740
TI  - Development of an in vitro system detecting pro-embryotoxin.
AB  - An in vitro system for detection of embryotoxins has been developed by using
      primary cultures of embryo fibroblasts. Various embryotoxins, including
      benzo[a]pyrene and thalidomide, have trivial cytotoxicity in embryo fibroblast
      systems, which is at least in part due to a lack of capacity for metabolic
      activation. Introduction of steps for microsomal pre-incubation and calcium
      precipitation prior to chemical contact resulted in the clear appearance of
      embryotoxicity toward thalidomide and benzo[a]pyrene. This pre-incubation method
      will offer advantages for the detection of embryotoxins, which require maternal
      metabolic activation, and for understanding the mechanisms of their metabolic
      activations.

PMID- 12184741
TI  - Vasopressin induces emesis in Suncus murinus.
AB  - This paper reports that vasopressin is emetogenic in the house musk shrew Suncus
      murinus. Either intravenous or intracerebroventricular administration of
      vasopressin caused vomiting within a few minutes. The ED50 of intravenous
      vasopressin was as high as 4.67 microg/kg, whereas intracerebroventricularly
      injected vasopressin was effective at a low dose of 20 ng/brain. The emetogenic
      target of vasopressin may therefore be present in the central nervous system. We
      propose the Suncus as a useful animal for investigation of vasopressin-mediated
      emesis, including motion sickness.

PMID- 12184742
TI  - Tin-capped trinuclear nickel clusters: redox isomerism between micro(3)-stannyl
      and micro(3)-stannylene clusters of the class [Ni(3)(dppm)(3)(micro3-I)(micro3
      SnCl(x)](n+) (x = 2, n = 1; x = 3, n = 0).
AB  - The reaction of Ni(3)(dppm)(3)(micro(3)-I)(2)) with sodium trichlorostannate
      affords the first tin-capped nickel cluster Ni(3)(dppm)(3)(micro(3)-I)(micro(3)
      SnCl(3) (1). A site of coordinative unsaturation at tin can be introduced by the
      reaction of 1 with Tl[PF(6)] yielding the stannylene-capped cluster
      [Ni(3)(dppm)(3)(micro(3)-I)(micro(3)-SnCl(2)](+) (2). Clusters 1 and 2 were
      characterized by 31P NMR, X-ray diffraction, and cyclic voltammetry (CV).
      Clusters 1 and 2 exhibit single electron redox chemistries,
      [Ni(3)(dppm)(3)(micro(3)-I)(micro(3)-SnCl3](0/*-), [Ni(3)(dppm)(3)(micro(3)
      I)(micro(3)-SnCl(2)](+/0), that together comprise a redox equilibrium. Thus,
      electrochemical reduction of 1 produces first the 49e- cluster radical anion
      [Ni(3)(dppm)(3)(micro(3)-I)(micro(3)-SnCl(3)](*-) which then yields the reduced
      form of 2, [Ni(3)(dppm)(3)(micro(3)-I)(micro(3)-SnCl(2)], upon chloride
      dissociation.

PMID- 12184743
TI  - Dichloromethane alkylates a trithiolato-ruthenium complex to yield a methylene
      bridged thioether core. Synthesis and structural comparison to the thiolato
      ruthenium precursor.
AB  - The previously reported triphosphino/trithiolato-ruthenium anion, [tris-(2
      diphenylphosphinothia-phenolato)ruthenium(II)](-), [Ru(DPPBT)(3)](-), has been
      isolated as the PPN salt (PPN = bis(triphenylphosphoranylidene) ammonium), 1,
      from chlorobenzene/ether as light-orange crystalline plates, and the X-ray
      crystal structure has been determined. In dichloromethane, the cis positioned
      thiolates are alkylated by solvent yielding the methylene-bridged
      triphosphino/dithioether/thiolato complex [(bis-(2
      diphenylphosphinothiaphenolato)methane)(2-diphenyl
      phosphinothiaphenolato)ruthenium(II)]chloride, [Ru((DPPBT)(2)CH(2))(DPPBT)]Cl
      (2). Dichloromethane solutions of 1 layered with hexanes yield 2 as orange cubes.
      The ruthenium-sulfur bond distances in the alkylated, thioether product are
      slightly shorter than in the thiolate precursor. Within 2, the iron-thioether
      bond distances are comparable to the iron-thiolate distances.

PMID- 12184744
TI  - Decomposition of ascorbic acid in the presence of cadmium ions leads to formation
      of a polymeric cadmium oxalate species with peculiar structural features.
AB  - Slow decomposition of L-ascorbic acid, carried out under aerobic conditions and
      in the presence of cadmium ions, results in formation of a crystalline product
      that is highly insoluble in water. This compound has been identified as a cadmium
      oxalate polymeric species with formula Cd(C(2)O(4)).3H(2)O. The crystal structure
      of this compound is described. Relevant crystal data are the following:
      C(4)H(12)O(14)Cd(2), fw = 508.94; triclinic; space group P1 (No. 1); a = 6.010(1)
      A, b = 6.668(1) A, c = 8.498(1) A; alpha = 74.64(1) degrees, beta = 74.25(1)
      degrees, gamma = 80.91(1) degrees; V = 314.7(5) A(3); Z = 1.

PMID- 12184745
TI  - The monophosphino urea derivative PPh(2)NMeC(O)NMeH: a hemilabile ligand
      switching between P,O- and P,N-coordination.
AB  - Treatment of N,N'-dimethyl urea with ClPPh(2) and NEt(3) as auxiliary base in thf
      affords the title compound PPh(2)NMeC(O)NMeH (1) in high yield. The monophosphino
      urea derivative 1 constitutes the first isolated and fully characterized
      representative of this class with a NH functional group. Evidence for a solvent
      effect in the synthesis of 1 is given and the X-ray crystal structure determined.
      The reaction of 1 with [Mo(CO)(4)(NCMe)(2)] and the hemilabile character of the
      ligand 1 in the obtained P,O-chelate complex cis-[Mo(CO)(4)(eta(2)
      PPh(2)NMeC(O)NMeH)] (2) are described. Furthermore, synthesis of the known
      bisphosphino urea derivative CO(NMePPh(2))(2) (3) starting from 1 is reported.

PMID- 12184746
TI  - Direct observation of competitive ultrafast CO dissociation and relaxation of an
      MLCT excited state: picosecond time-resolved infrared spectroscopic study of
      [Cr(CO)(4)(2,2'-bipyridine)].
AB  - Early excited-state dynamics of [Cr(CO)(4)(bpy)] were studied in a CH(2)Cl(2)
      solution by picosecond time-resolved IR spectroscopy, which made it possible to
      characterize structurally the individual species involved and to follow
      separately the temporal evolution of the IR bands due to the bleached ground
      state absorption, the fac-[Cr(CO)(3)(Sol)(bpy)] photoproduct, and two (3)MLCT
      states. It was found that the fac-[Cr(CO)(3)(Sol)(bpy)] photoproduct is formed
      alongside population of two (3)MLCT states during the first picosecond after
      excitation at 400 or 500 nm by a branched evolution of the optically populated
      excited state. Vibrationally relaxed (3)MLCT excited states are unreactive,
      decaying directly to the ground state on a picosecond time scale. The
      photoproduct is long-lived, persistent into the nanosecond time domain. Changing
      the excitation wavelength from 400 to 500 nm strongly increases the extent of the
      bleach recovery and decreases the yield of the photoproduct formation relative to
      the initial yield of the population of the unreactive (3)MLCT states. The
      photochemical quantum yield of CO dissociation also decreases with increasing
      excitation wavelength (Vichova, J.; Hartl, F.; Vlcek, A., Jr. J. Am. Chem. Soc.
      1992, 114, 10903). These observations demonstrate the relationship between the
      early dynamics of optically populated excited states and the overall outcome of a
      photochemical reaction and identify the limiting role of the branching of the
      initial excited-state evolution between reactive and relaxation pathways as a
      more general principle of organometallic photochemistry.

PMID- 12184747
TI  - Sulfur-bridged early-late heterobimetallics synthesized by incorporation of
      titanium, vanadium, and molybdenum into bis(hydrosulfido) templates of group 9
      metals.
AB  - Reactions of the bis(hydrosulfido) complexes [Cp*Rh(SH)(2)(PMe(3))] (1a; Cp* =
      eta(5)-C(5)Me(5)) with [CpTiCl(3)] (Cp = eta(5)-C(5)H(5)) and [TiCl(4)(thf)(2)]
      in the presence of triethylamine led to the formation of the sulfido-bridged
      titanium-rhodium complexes [Cp*Rh(PMe(3))(micro(2)-S)(2)TiClCp] (2a) and
      [Cp*Rh(PMe(3))(micro2-S)(2)TiCl(2)] (3a), respectively. Complex 3a and its
      iridium analogue 3b were further converted into the bis(acetylacetonato)
      complexes [Cp*M(PMe(3))(micro(2)-S)(2)Ti(acac)(2)] (4a, M = Rh; 4b, M = Ir) upon
      treatment with acetylacetone. The hydrosulfido complexes 1a and
      [Cp*Ir(SH)(2)(PMe(3))] (1b) also reacted with [VCl(3)(thf)(3)] and
      [Mo(CO)(4)(nbd)] (nbd = 2,5-norbornadiene) to afford the cationic sulfido-bridged
      VM2 complexes [(Cp*M(PMe(3))(micro2-S)(2))2V](+) (5a(+), M = Rh; 5b(+), M = Ir)
      and the hydrosulfido-bridged MoM complexes [Cp*M(PMe(3))(micro2-SH)(2)Mo(CO)(4)]
      (6a, M = Rh; 6b, M = Ir), respectively.

PMID- 12184748
TI  - Reductive growth of nanosized ligated metal clusters on silicon nanowires.
AB  - The reductive growth of metal clusters on silicon nanowires (SiNWs) is reported.
      The HF-etched SiNWs were found to reduce ligated Au-Ag clusters of single size,
      shape, composition, and structure. In the process, the surfaces of the SiNWs were
      reoxidized. The reductive cluster growth on the SiNW surface was followed by high
      resolution transmission electron microscopy (HRTEM). The reduced metal clusters
      grew to different sizes in the nanometer regime (1-7 nm in diameter) on the SiNW
      surfaces. At sizes greater than approximately 7 nm, they tend to separate from
      the SiNW surfaces. Further growth and/or agglomeration of these colloidal
      particles to sizes greater than roughly 25 nm in diameter eventually causes the
      particles to precipitate from solution. Two interesting phenomena, the "sinking
      cluster" and the "cluster fusion" processes, were observed under TEM.

PMID- 12184749
TI  - Lead(II) complexes with macrocyclic receptors derived from 4,13-diaza-18-crown-6.
AB  - The complexation properties of three related macrocycles derived from 4,13-diaza
      18-crown-6 toward lead(II) are reported. The flexible macrocycle N,N'-bis(2
      aminobenzyl)-4,13-diaza-18-crown-6 (L(2)) forms stable complexes with this metal
      ion in the presence of different counterions (perchlorate and thiocyanate). The X
      ray crystal structure of [PbL(2)](SCN)(2) indicates that, in the solid state, the
      lead(II) ion is eight-coordinated and fits quite well into the crown hole
      favoring an anti arrangement of the organic receptor, which generates a very
      infrequent cubic coordination polyhedron around the Pb(II) ion. In solution both
      complexes are fluxional and the nature of the counterion seems to affect the
      dynamic behavior. Ligand L(3), N,N'-bis[(2-salicylaldimino)benzyl]-4,13-diaza-18
      crown-6, derives from L(2) by condensation of salicylaldehyde with the amine
      group of each side arm. It can be deprotonated to yield cationic complexes of
      formula [Pb(L(3)-H)](+) where the metal ion lies asymmetrically on the cavity of
      the ligand, being seven-coordinated and pushed out from the crown hole, the
      bibracchial lariat ether presents a syn arrangement, and one of the arms remains
      uncoordinated. The lead(II) ion also lies asymmetrically on the cavity of the
      third macrocycle (L(7)), a lateral macrobicycle incorporating a phenolyl Schiff
      base spacer. Spectrophotometric titrations of L(2) and (L(3)-2H)(2)(-) with
      lead(II) perchlorate in acetonitrile gave values of log K[PbL(2)] = 7.7(5) and
      log K[Pb(L(3)-2H)] = 7.2(3), demonstrating that the stability of the lead(II)
      complexes with these two ligands is very similar.

PMID- 12184750
TI  - Syntheses and X-ray structures of potassium derivatives and a paramagnetic
      nickel(II) complex of a cyclodiphosph(III/V)azane monoselenide.
AB  - The cyclodiphosph(III/V)azane monoselenide [(t)Bu(H)N(Se)P(micro
      N(t)Bu)(2)PN(H)(t)Bu] (6, H(2)cdppSe where cdpp = cyclodiphosphazane) is obtained
      in quantitative yield from the comproportionation reaction of equimolar amounts
      of H(2)cdpp (7) and H(2)cdppSe(2) (3) in toluene at 85 degrees C. The X-ray
      structures of 3 and 6 reveal that both the monoselenide and the diselenide adopt
      a cis,endo,exo arrangement of the (t)BuNH groups. Metalation of 6 with 1 equiv of
      KO(t)Bu or 2 equiv of KCH(2)Ph in THF produces [(THF)K[HcdppSe]](2) (8) or
      [[(THF)(2)K](2)[cdppSe]](2) (9), respectively. The initial deprotonation involves
      the (t)BuNH group attached to the P(V) center in 6. In the dimeric structure of
      8, both of the monoanionic ligands are bis-N,Se-chelated to the two K(+) cations
      to give a distorted K(2)N(2)Se(2) octahedron. In the centrosymmetric dimer 9, the
      dianionic ligands adopt two different coordination modes to the bis-solvated K(+)
      ions, viz., tridentate N,N',N" coordination and N,Se-chelation involving both exo
      and endocyclic nitrogen atoms. The dimer is linked through K-Se interactions.
      The reaction of 2 equiv of 8 with NiCl(2)(PMe(3))(2) in THF produces
      [Ni(HcdppSe)(2)], which has a distorted tetrahedral structure and exhibits
      anomalous (1)H, (13)C, and (31)P NMR chemical shifts owing to the proximity of
      the paramagnetic Ni(II) center.

PMID- 12184751
TI  - A DFT study of SiH(4) activation by Cp(2)LnH.
AB  - A theoretical study of SiH(4) activation by Cp(2)LnH complexes for the entire
      series of lanthanides has been carried out at the DFT-B3PW91 level of theory. The
      reaction paths corresponding to H/H exchange and silylation, formation of
      Cp(2)Ln(SiH(3)), have been computed. They both occur via a single-step sigma-bond
      metathesis mechanism. For the athermal H/H exchange reaction, the calculated
      activation barrier averages 1.8 kcal.mol(-)(1) relative to the precursor adduct
      Cp(2)LnH(eta(2)-SiH(4)) for all lanthanide elements. The silylation path is
      slightly exogenic (DeltaE approximately -6.5 kcal.mol(-1)) with an activation
      barrier averaging 5.2 kcal.mol(-1) relative to the precursor adduct where SiH(4)
      is bonded by two Si-H bonds. Both pathways are therefore thermally accessible.
      The H/H exchange path is calculated to be kinetically more favorable whereas the
      silylation reaction is thermodynamically preferred. The reactivity of this
      familly of lanthanide complexes with SiH(4) contrasts strongly with that obtained
      previously with CH(4). The considerably lower activation barrier for silylation
      relative to methylation is attributed to the ability of Si to become hypervalent.

PMID- 12184752
TI  - Synthesis, magnetic properties, and electronic spectra of Bis(beta
      diketonato)chromium(III) and nickel(II) complexes with a chelated imino nitroxide
      radical: X-ray structures of [Cr(acaMe)(2)(IM2py)]PF(6) and [Ni(acac)(2)(IM2py)].
AB  - Two new series of each of four Cr(III) and Ni(II) imino nitroxide complexes with
      various kinds of beta-diketonates, [Cr(beta-diketonato)(2)(IM2py)]PF(6), and
      [Ni(beta-diketonato)(2)(IM2py)] (IM2py = 2-(2'-(pyridyl)-4,4,5,5-tetramethyl-4,5
      dihydro-1H-imidazol-1-oxy)) have been synthesized, and their structures and
      magnetic and optical properties have been examined. The X-ray analysis
      demonstrated that a IM2py ligand coordinated to Cr(III) and Ni(II) acts as a five
      membered bidentate chelate. The variable-temperature magnetic susceptibility
      measurements indicated the antiferromagnetic and ferromagnetic interaction of
      Cr(III) and Ni(II) with IM2py, respectively, giving a variety of the magnetic
      coupling constant J values with varying the beta-diketonato ligands. The UV-vis
      shoulders around (19-20) x 10(3) and (17-18) x 10(3) cm(-)(1) for the Cr(III) and
      Ni(II) complexes, respectively, characteristic of the IM2py complexes were
      assigned to the metal-ligand charge-transfer transitions, Cr(t(2g))-SOMO(pi*) and
      Ni(e(g))-SOMO(pi*) MLCT in terms of the resonance Raman spectra and the variable
      temperature absorption spectra. The absorption components centered around (13-14)
      x 10(3) cm(-1) for the Cr(III) and Ni(II) complexes were due to the formally spin
      forbidden d-d transition within the t(2g) and e(g) subshells, associated with the
      intensity enhancement. The spectroscopic behavior with varying the beta
      diketonato ligands is discussed in connection with the antiferromagnetic or
      ferromagnetic coupling constant J values on the basis of the exchange mechanism
      along with the coligand effect.

PMID- 12184753
TI  - A new tantalum dinitrogen complex and a parahydrogen-induced polarization study
      of its reaction with hydrogen.
AB  - Reduction of Cp*(2)TaCl(2) with sodium amalgam in THF under a nitrogen atmosphere
      results in the formation of the novel complex (Cp*(2)TaCl)(2)(micro-N(2)). This
      dinuclear complex containing a micro-eta(1):eta(1) dinitrogen bridge has been
      characterized by NMR and X-ray crystallography. The complex possesses a C(2)
      symmetric structure with each Ta bound to diastereotopic Cp* rings and chloride
      in addition to the micro-N(2) bridge. The Ta-N and N-N distances of 1.885(10) and
      1.23(1) A, respectively, suggest modest reduction of the dinitrogen moiety. The
      two Cp* resonances on each Ta center remain inequivalent in solution, even up to
      80 degrees C. Addition of hydrogen results in the formation of two isomers of the
      dihydride complex Cp*(2)TaH(2)Cl. Under parahydrogen, polarized resonances are
      observed for the unsymmetrical isomer with adjacent hydrides as the product of
      H(2) oxidative addition. The symmetric isomer of Cp*(2)TaH(2)Cl also forms, most
      likely by isomerization of the unsymmetrical kinetic isomer. The reactivity of
      (Cp*(2)TaCl)(2)(micro-N(2)) was compared to that of the related monomer,
      Cp*(2)TaCl(THF). The THF adduct yields the same hydrogen addition products, but
      the reaction is much more facile than for the nitrogen dimer, indicative of the
      structural integrity of the micro-N(2) complex.

PMID- 12184754
TI  - Ionic hydrates, M(p)X(q).nH(2)O: lattice energy and standard enthalpy of
      formation estimation.
AB  - This paper is one of a series (see: Inorg. Chem. 1999, 38, 3609; J. Am. Chem.
      Soc. 2000, 122, 632; Inorg. Chem. 2002, 41, 2364) exploring simple approaches for
      the estimation of lattice energies of ionic materials, avoiding elaborate
      computation. Knowledge of lattice energy can lead, via thermochemical cycles, to
      the evaluation of the underlying thermodynamics involving the preparation and
      subsequent reactions of inorganic materials. A simple and easy to use equation
      for the estimation of the lattice energy of hydrate salts,
      U(POT)(M(p)X(q).nH(2)O) (and therefore for solvated salts, M(p)X(q).nS, in
      general), using either the density or volume of the hydrate, or of another
      hydrate, or of the parent anhydrous salt or the volumes of the individual ions,
      is derived from first principles. The equation effectively determines the hydrate
      lattice energy, U(POT)(M(p)X(q).nH(2)O), from a knowledge of the (estimated)
      lattice energy, U(POT)(M(p)X(q)), of the parent salt by the addition of ntheta(U)
      where theta(U)(H(2)O)/kJ mol(-1) = 54.3 and n is the number of water molecules.
      The average volume of the water molecule of hydration, V(m)(H(2)O)/nm(3) =
      0.0245, has been determined from data on a large series of hydrates by plotting
      hydrate/parent salt volume differences against n. The enthalpy of incorporation
      of a gaseous water molecule into the structure of an ionic hydrate, [Delta(f)H
      degrees (M(p)X(q).nH(2)O,s) - Delta(f)H degrees (M(p)X(q),s) - nDelta(f)H degrees
      (H(2)O,g)], is shown to be a constant, -56.8 kJ (mol of H(2)O)(-1). The physical
      implications with regard to incorporation of the water into various types of
      solid-state structures are considered. Examples are given of the use of the
      derived hydrate lattice energy equation. Standard enthalpies of formation of a
      number of hydrates are thereby predicted.

PMID- 12184755
TI  - Excited-state electronic coupling and photoinduced multiple electron transfer in
      two related ligand-bridged hexanuclear mixed-valence compounds.
AB  - The synthesis, characterization, electrochemical, photophysical, and
      photochemical properties of two hexanuclear mixed-valence compounds are reported.
      Each supramolecular species consists of two cyano-bridged [(NC)(5)Fe(II)-CN
      Pt(IV)(NH(3))(3)L-NC-Fe(II)(CN)(5)] triads that are linked to each other through
      a Pt(IV)-L-Pt(IV) bridge, where L = 4,4'-dipyridyl (bpy) or 3,3'-dimethyl-4,4'
      dipyridyl (dmb). The major difference between the two compounds is the electronic
      nature of the bridging ligand between the two Pt atoms. Both species exhibit a
      broad Fe(II) --> Pt(IV) intervalent (IT) absorption band at 421 nm with an
      oscillator strength that is approximately four times that for [(NC)(5)Fe(II)-CN
      Pt(IV)(NH(3))(5)] and twice that for [(NC)(5)Fe(II)-CN-Pt(IV)(NH(3))(4)-NC
      Fe(II)(CN)(5)].(4-) When L = bpy, the resonance Raman spectrum obtained by
      irradiating the IT band at 488 nm exhibits several dipyridyl ring modes at 1604,
      1291, and 1234 cm(-1) which are not present in the spectrum when L = dmb. In
      addition, femtosecond pump-probe spectroscopy performed at 400 nm yields a
      transient bleach of the IT absorption band with a single exponential decay of 3.5
      ps for L = bpy, compared with only 1.8 ps for L = dmb and 2.1 ps for
      [(NC)(5)Fe(II)-CN-Pt(IV)(NH(3))(4)-NC-Fe(II)(CN)(5)].(4-) Last, prolonged
      irradiation of the complexes at 488 nm leads to the formation of 4 equiv of
      ferricyanide with a quantum efficiency of 0.0014 for L = bpy and 0.0011 for L =
      dmb. The transient absorption, resonance Raman, and photochemical data suggest
      that the degree of excited electronic coupling in these compounds is tunable by
      changing the electronic nature of the Pt-L-Pt bridging ligand.

PMID- 12184756
TI  - Tetracyanometalates of Ni, Pd, and Pt with cyclic diquaternary cations of 2,2'
      bipyridine and 1,10-phenanthroline. A vibrational, crystallographic, and
      theoretical study of intermolecular weak interactions.
AB  - The compounds (bpy-dq)[Ni(CN)(4)].2H(2)O (1), (bpy-dq)[Pd(CN)(4)].2H(2)O (2), and
      ((bpy-dq)[Pt(CN)(4)].2H(2)O (3) (bpy-dq = (C(12)H(12)N(2))(2+), 6,7
      dihydrodipyrido[1,2-a:2',1'-c]pyrazinediium) and (phen-dq)[Ni(CN)(4)] (4), (phen
      dq)[Pd(CN)(4)].H(2)O (5), and (phen-dq)[Pt(CN)(4)].H(2)O (6) (phen-dq =
      (C(14)H(12)N(2))(2+), 5,6-dihydropyrazino[1,2,3,4-lmn]-1,10-phenanthrolinediium)
      have been synthesized and characterized by X-ray diffraction. The three
      bipyridinium diquaternary salt derivatives are isostructural. The crystal
      structures of these dihydrated compounds consist of columns formed by alternating
      anion complexes and diquaternary cations, pi-pi interacting through cyanide
      ligands and the aromatic rings, and stabilized by an extended hydrogen-bond
      network. On the other hand, the packing in the phenanthrolinium diquaternary salt
      derivatives is strongly dependent on the hydration degree. Thus, the anhydrous
      [Ni(CN)(4)](2-) compound presents a laminar arrangement and the hydrated salts
      show a columnar packing, similar but not the same as compounds 1-3. The anhydrous
      form of compound 5 is isostructural with compound 4. Vibrational (IR, Raman) and
      thermogravimetric studies of these compounds have been carried out. Finally, DFT
      calculations have been performed on the isolated tetracyanometalate anions and
      diquaternary cations to assign the fundamental modes in the vibrational spectra.
      The intermolecular weak interactions were studied through the analysis of the
      charge density by using the theory of atoms in molecules (AIM).

PMID- 12184757
TI  - Polynuclear complexes of the pendent-arm ligand 1,4,7-tris(acetophenoneoxime)
      1,4,7-triazacyclononane.
AB  - The ligand 1,4,7-tris(acetophenoneoxime)-1,4,7-triazacyclononane (H(3)L) has been
      synthesized and its coordination properties toward Cu(II), Ni(II), Co(II), and
      Mn(II) in the presence of air have been investigated. Copper(II) yields a
      mononuclear complex, [Cu(H(2)L)](ClO(4)) (1), cobalt(II) and manganese(II) ions
      yield mixed-valence Co(III)(2)Co(II) (2a) and Mn(II)(2)Mn(III) (4) complexes,
      whereas nickel(II) produces a tetranuclear [Ni(4)(HL)(3)](2+) (3) complex. The
      complexes have been structurally, magnetochemically, and spectroscopically
      characterized. Complex 3, a planar trigonal-shaped tetranuclear Ni(II) species,
      exhibits irregular spin-ladder. Variable-temperature (2-290 K) magnetic
      susceptibility analysis of 3 demonstrates antiferromagnetic exchange interactions
      (J = -13.4 cm(-1)) between the neighboring Ni(II) ions, which lead to the ground
      state S(t) = 2.0 owing to the topology of the spin-carriers in 3. A bulk
      ferromaganetic interaction (J = +2 cm(-1)) is prevailing between the neighboring
      high-spin Mn(II) and high-spin Mn(III) ions leading to a ground state of S(t) =
      7.0 for 4. The large ground-state spin value of S(t) = 7.0 has been confirmed by
      magnetization measurements at applied magnetic fields of 1, 4 and 7 T. A bridging
      monomethyl carbonato ligand formation occurs through an efficient CO(2) uptake
      from air in methanolic solutions containing a base in the case of complex 4.

PMID- 12184758
TI  - Density functional calculations for modeling the oxidized states of the active
      site of nickel-iron hydrogenases. 1. Verification of the method with paramagnetic
      Ni and Co complexes.
AB  - ZORA relativistic DFT calculations are presented which aim to reproduce geometric
      structures and EPR properties of [Ni(mnt)(2)](-) (H(2)mnt = maleonitrildithiol),
      two other paramagnetic low-spin Ni(III) complexes, and an asymmetric paramagnetic
      Co(II) complex. The study tests the accuracy of the computational method as a
      prior step to the modeling of the geometric and electronic structure of the
      active site of NiFe hydrogenases in its EPR-active oxidized states Ni-A and Ni-B.
      Systematic deviations from experiment are found for the calculated g-values;
      relative differences among them are, however, well reproduced. Because no
      significant improvements have been achieved by using larger basis sets or more
      sophisticated functionals, g-values may be calculated rather rapidly at the VWN
      level. This is most important for the modeling of the active site of NiFe
      hydrogenases because its complexity does not permit calculations at high levels
      of theory. For [Ni(mnt)(2)](-), excellent agreement between calculated and
      experimental results is obtained for the (14)N quadrupole coupling, whereas the
      calculated hyperfine couplings are not always in good agreement with experimental
      data.

PMID- 12184760
TI  - Preparation and structural characterization of ionic five-coordinate
      palladium(II) and platinum(II) complexes of the ligand tris[2
      (diphenylphosphino)ethyl]phosphine. Insertion of SnCl(2) into M-Cl bonds (M = Pd,
      Pt) and hydroformylation activity of the Pt-SnCl(3) systems.
AB  - The five-coordinate palladium(II) and platinum(II) complexes [M(PP(3))Cl]Cl [M =
      Pd (1), Pt (2)] (PP(3) = tris[2-(diphenylphosphino)ethyl]phosphine) were prepared
      by interaction of aqueous solutions of MCl(4)(2-) salts with PP(3) in CHCl(3).
      Complexes 1 and 2 undergo facile chloro substitution reactions with KCN in 1:1
      and 1:2 ratios to afford complexes [M(PP(3))(CN)]Cl [M = Pt (3)] and
      [M(PP(3))(CN)](CN) [M = Pd (4), Pt (5)] possessing M-C bonds, both in solution
      and in the solid state. The reaction of 1 and 2 with SnCl(2) in CDCl(3) occurs
      with insertion of SnCl(2) into M-Cl bonds leading to the formation of
      [M(PP(3))(SnCl(3))](SnCl(3)) [M = Pd (6), M = Pt (7)]. The isolation as solids of
      complexes 6 and 7 by addition of SnCl(2) to the precursors requires the presence
      of PPh(3) which activates the cleavage of M-Cl bonds, favors the SnCl(2)
      insertion, and does not coordinate to M in any observable extent. Solutions of 6
      in CDCl(3) undergo tin dichloride elimination in higher proportion than solutions
      of 7. The reaction of complexes 1 and 2 with SnPh(2)Cl(2) leads to
      [M(PP(3))Cl](2)[SnPh(2)Cl(4)] [M = Pd (8)]. Complexes 2, 5, 7, and 8 were shown
      by X-ray diffraction to contain distorted trigonal bipyramidal monocations
      [M(PP(3))X](+) [M = Pt, X = Cl(-) (2), X = CN(-) (5), X = SnCl(3)(-) (7); M = Pd,
      X = Cl(-) (8)], the central P atom of PP(3) being trans to X in axial position
      and the terminal P donors in the equatorial plane of the bipyramids. The
      "preformed" catalyst 7 showed a relatively high aldehyde selectivity compared to
      most of the platinum catalysts.

PMID- 12184761
TI  - Synthesis and ligand-based mixed valency of cis- and trans
      Cr(III)(X(4)SQ)(X(4)Cat)(L)(n) (X = Cl and Br, n = 1 or 2) complexes: effects of
      solvent media on intramolecular charge distribution and ligand dissociation of
      Cr(III)(X(4)SQ)(3).
AB  - The treatment of Cr(III)(X(4)SQ)(3) (SQ = o-semiquinonate; X = Cl and Br) with
      acetonitrile affords trans-Cr(III)(X(4)SQ)(X(4)Cat)(CH(3)CN)(2) (X = Cl (1) and
      Br (2)). In the presence of 2,2'-bipyridine (bpy) or 3,4,7,8-tetramethyl-1,10
      phenanthrene (tmphen), the reaction affords
      Cr(III)(X(4)SQ)(X(4)Cat)(bpy).nCH(3)CN (X = Cl, n = 1 (3); X = Br, n = 0.5 (4))
      or Cr(III)(X(4)SQ)(X(4)Cat)(tmphen) (X = Cl (5) and Br (6)), respectively. All of
      the complexes show a ligand-based mixed-valence (LBMV) state with SQ and Cat
      ligands. The LBMV state was confirmed by the presence of the interligand
      intervalence charge-transfer band. Spectroscopic studies in several solvent media
      demonstrate that the ligand dissociation included in the conversion of
      Cr(III)(X(4)SQ)(3) to 1-6 occurs only in solvents with relatively high polarity.
      On the basis of these results, the effects of solvent media were examined and an
      equilibrium, Cr(III)(X(4)SQ)(3) <--> Cr(III)(X(4)BQ)(X(4)SQ)(X(4)Cat) (BQ = o
      benzoquinone), is proposed by assuming an interligand electron transfer induced
      by solvent polarity.

PMID- 12184759
TI  - Density functional calculations for modeling the active site of nickel-iron
      hydrogenases. 2. Predictions for the unready and ready States and the
      corresponding activation processes.
AB  - ZORA relativistic DFT calculations are presented which aim to model the geometric
      and electronic structure of the active site of NiFe hydrogenases in its EPR
      active oxidized states Ni-A (unready state) and Ni-B (ready state). Starting
      coordinates are taken from the X-ray structure of a mutant of Desulfovibrio
      fructosovorans hydrogenase refined at 1.81 A resolution. Nine possible candidates
      for Ni-A and Ni-B are analyzed in terms of their geometric and electronic
      structure. Comparison of calculated geometric and magnetic resonance parameters
      with available experimental data indicates that both oxidized states have a micro
      hydroxo bridge between the two metal centers. The different electronic structures
      of both forms can be explained by a modification of a terminal cysteine in Ni-B,
      best modeled by protonation of the sulfur atom. A possible mechanism for the
      activation of both oxidized forms is presented.

PMID- 12184762
TI  - Solid-state structural and magnetic investigations of [M[HC(3,5
      Me(2)pz)(3)](2)](BF(4))(2) (M = Fe, Co, Ni, Cu): observation of a thermally
      induced solid-state phase change controlling an iron(II) spin-state crossover.
AB  - The reaction of M(BF(4))(2).xH(2)O (M = Co, Ni, and Cu) and HC(3,5-Me(2)pz)(3) in
      a 1:2 ratio yields [Co[HC(3,5-Me(2)pz)(3)](2)](BF(4))(2) (2), [Ni[HC(3,5
      Me(2)pz)(3)](2)](BF(4))(2) (3), and [Cu[HC(3,5-Me(2)pz)(3)](2)](BF(4))(2) (4).
      Over the temperature range from 5 to 350, 345, or 320 K, Curie law behavior is
      observed for microcrystalline samples of all three compounds showing them to have
      three, two, and one unpaired electrons, respectively, with no spin-crossover
      observed for 2. Crystalline samples of these compounds torque in the applied
      magnetic field the first time the sample is cooled to 5 K. The solid-state
      structures of all three are isomorphous at 220 K, monoclinic in the space group
      C2/c. The metal is located on a unique crystallographic site and has a trigonally
      distorted octahedral structure, with 4 showing the expected Jahn-Teller
      distortions. Cooling crystals of all three to low temperatures leads to the
      observation of the same phase change to triclinic in the new space group P(-)1
      with nonmerohedral twinning. This change is reversible and yields two
      crystallographically unique metal sites at low temperature. The bond angles and
      distances for the two different metal sites for each compound in the low
      temperature structures are very similar to each other and to those in the 220 K
      structures. The same phase change, monoclinic to triclinic, has been observed
      previously for [Fe[HC(3,5-Me(2)pz)(3)](2)](BF(4))(2) (1), except in this case,
      the phase change results in half of the cations changing over from the high-spin
      state to the low-spin state while the other half of the cations remain high-spin,
      with the low-spin form decreasing its Fe-N bond distances by 0.19 A. The new
      results with 2-4 show that it is the phase transition, which occurs in complexes
      of the type [M[HC(3,5-Me(2)pz)(3)](2)](BF(4))(2) with first row transition
      metals, that is driving the unusual spin-crossover behavior of [Fe[HC(3,5
      Me(2)pz)(3)](2)](BF(4))(2).

PMID- 12184763
TI  - Site specificity of metal ions in heterodinuclear complexes derived from an "end
      off" compartmental ligand.
AB  - A phenol-based "end-off" compartmental ligand, 2-[N-[2
      (dimethylamino)ethyl]iminomethyl]-6-[N,N-di(2-pyridylmethyl)aminomethyl]-4
      methylphenol (HL), having a bidentate arm and a tridentate arm attached to the 2
      and 6 positions of the phenolic ring, has afforded the following heterodinuclear
      M(a)(II)M(b)(II) complexes: [CuM(L)(AcO)(2)]ClO(4) (M = Mn (1), Fe (2), Co (3),
      Ni (4), Zn (5)), [ZnM(L)(AcO)(2)]ClO(4) (M = Co (6), Ni (7)), and
      [CuNi(L)(AcO)(NCS)(2)] (8). 1.MeOH (1'), 2.MeOH (2'), 3.MeOH (3'), 4.MeOH (4'),
      5.MeOH (5'), and 7.MeOH (7') are isostructural and have a heterodinuclear core
      bridged by the phenolic oxygen atom of L(-) and two acetate groups. In 1'-5' the
      Cu(II) is bound to the bidentate arm and has a square-pyramidal geometry with one
      acetate oxygen at the apical site. The M(II) is bound to the tridentate arm and
      has a six-coordinate geometry together with two acetate oxygen atoms. In the case
      of 7' the Zn is bound to the bidentate arm and the Ni is bound to the tridentate
      arm. 8.2-PrOH (8') has a dinuclear core bridged by the phenolic oxygen atom of L(
      ) and one acetate group. The Cu bound to the bidentate arm has a square-pyramidal
      geometry with an isothiocyanate group at the apical site. The Ni bound to the
      tridentate arm has a six-coordinate geometry with further coordination of an
      isothiocyanate group. The site specificity of the metal ions is discussed
      together with the crystal structure of [Cu(4)(L)(2)(AcO)(3)](ClO(4))(3).H(2)O (9)
      prepared in this work.

PMID- 12184764
TI  - Synthesis and catalytic application of octahedral lewis base adducts of dichloro
      and dialkyl dioxotungsten(VI).
AB  - Complexes of the composition W(O)(2)(Cl)(2)L(2) and W(O)(2)(R)(2)L(2) (R = Me,
      Et; L(2) = bidentate Lewis base ligand) have been prepared and are fully
      characterized (including an exemplary X-ray crystal structure of
      W(O)(2)(Cl)(2)(4,4'-di-tert-butyl-2,2'-bipyridine)). This latter compound
      crystallizes in the orthorhombic space group P2(1)2(1)2(1) with a = 8.3198(1) A,
      b = 13.3224(2) A, c = 18.0415(2) A, and Z = 4. The title complexes are applied as
      catalysts in olefin epoxidation catalysis with tert-butyl hydroperoxide (TBHP) as
      the oxidizing agent. The W(VI) complexes display only moderate turnover
      frequencies but can be reused several times without loss of catalytic activity.
      The highest activity can be achieved at reaction temperatures of ca. 90 degrees
      C. Chloro derivatives are somewhat more active than alkyl complexes, and
      sterically less crowded complexes show also higher activities than their
      congeners with bulky ligands L(2). Kinetic examinations show that the catalyst
      formation is the rate determining step and it is observed that tert-butyl
      alcohol, the byproduct of the epoxidation reaction, acts as a competitor for
      TBHP, thus lowering the reaction velocity during the course of the reaction but
      not irreversibly destroying the catalyst.

PMID- 12184765
TI  - EPR spectra from "EPR-silent" species: high-frequency and high-field EPR
      spectroscopy of pseudotetrahedral complexes of nickel(II).
AB  - High-frequency and high-field electron paramagnetic resonance (HFEPR)
      spectroscopy (using frequencies of approximately 90-550 GHz and fields up to
      approximately 15 T) has been used to probe the non-Kramers, S = 1, Ni(2+) ion in
      a series of pseudotetrahedral complexes of general formula NiL(2)X(2), where L =
      PPh(3) (Ph = phenyl) and X = Cl, Br, and I. Analysis based on full-matrix
      solutions to the spin Hamiltonian for an S = 1 system gave zero-field splitting
      parameters: D = +13.20(5) cm(-1), /E/ = 1.85(5) cm(-1), g(x) = g(y) = g(z) =
      2.20(5) for Ni(PPh(3))(2)Cl(2). These values are in good agreement with those
      obtained by powder magnetic susceptibility and field-dependent magnetization
      measurements and with earlier, single-crystal magnetic susceptibility
      measurements. For Ni(PPh(3))(2)Br(2), HFEPR suggested /D/ = 4.5(5) cm(-1), /E/ =
      1.5(5) cm(-1), g(x) = g(y) = 2.2(1), and g(z) = 2.0(1), which are in agreement
      with concurrent magnetic measurements, but do not agree with previous single
      crystal work. The previous studies were performed on a minor crystal form, while
      the present study was performed on the major form, and apparently the electronic
      parameters differ greatly between the two. HFEPR of Ni(PPh(3))(2)I(2) was
      unsuccessful; however, magnetic susceptibility measurements indicated /D/ =
      27.9(1) cm(-1), /E/ = 4.7(1), g(x) = 1.95(5), g(y) = 2.00(5), and g(z) = 2.11(5).
      This magnitude of the zero-field splitting ( approximately 840 GHz) is too large
      for successful detection of resonances, even for current HFEPR spectrometers. The
      electronic structure of these complexes is discussed in terms of their molecular
      structure and previous electronic absorption spectroscopic studies. This
      analysis, which involved fitting of experimental data to ligand-field parameters,
      shows that the halo ligands act as strong pi-donors, while the triphenylphosphane
      ligands are pi-acceptors.

PMID- 12184766
TI  - Characterization of the side-on coordinated bissuperoxo complexes of aluminum
      FAl(O(2))(2), ClAl(O(2))(2), and BrAl(O(2))(2) with triplet electronic ground
      states: a combined matrix IR and quantum chemical study.
AB  - Matrix isolation has been used to study the photolytically induced reaction of
      AlX (X = F, Cl, or Br) with O(2). The peroxo and bisperoxo compounds XAlO(2) and
      XAl(O(2))(2) are found to be the products of these reactions. While the peroxo
      species XAlO(2) were already addressed in a separate work, we concentrate herein
      on the bissuperoxo complexes XAl(O(2))(2), which are to our knowledge the first
      examples of such complexes with Al centers. Our IR spectroscopic results taking
      in the effect of isotopic substitution ((16)O/(18)O) allied with quantum chemical
      calculations show that the O(2) moieties in these complexes are side-on
      coordinated, leading to an overall C(2)(v)() symmetry of the complexes and a spin
      multiplicity of 3. The O-O distance of about 1.366 A argues for the presence of
      superoxide units. The force constants are, however, somewhat smaller than
      expected for a superoxide anion and indicate that the bonding in the complexes
      cannot be described simply on the basis of an ionic model. Interestingly a
      photoinduced intramolecular isotopic scrambling process is observed for the
      compounds resulting in partial conversion of the XAl((16)O(2))((18)O)(2)
      isotopomer into XAl((16)O(18)O)((16)O(18)O). The properties of the complexes will
      be compared to those of complexes to transition metal centers.

PMID- 12184767
TI  - Three-dimensional open-framework neodymium oxalates with organic functional
      groups protruding in 12-member channels.
AB  - Two open-framework neodymium oxalates,
      [NH(3)CH(2)CH(NH(3))CH(3)][Nd(C(2)O(4))(2)(HCOO)].H(2)O (I) and
      [OC(CH(3))NCH(2)CH(CH(3))NH(3)][Nd(C(2)O(4))(2)].H(2)O (II), have been
      synthesized hydrothermally in the presence of 1,2-diaminopropane (1,2-DAP) and
      formic (I) and acetic (II) acids. The Nd atoms in both these oxalates have 9-fold
      coordination with respect to the oxygens, with the Nd atom in a distorted
      monocapped square antiprism coordination in I and in an idealized D(3)(h) triply
      capped trigonal prism coordination in II. The three-dimensional framework
      structures of I and II are built up by in-plane linkages between the Nd and the
      oxalate moieties, forming layers with 12-membered honeycomb-like apertures,
      pillared by an out-of-plane oxalate unit. The 12-memberd channel in I contains a
      dangling formate group in addition to the disordered amine molecule, while in II,
      the channel has N-(2-aminopropyl acetimide) molecules formed by the in situ
      reaction of 1,2-DAP and acetic acid. The accessibility of the formate and N-(2
      aminopropyl acetimide) functional groups in I and II, respectively, uniformly
      distributed within the channels enables chemical manipulation. Crystal data: I,
      monoclinic, space group P2(1)/c (no. 14), M = 459.5, a = 9.0279(4) A, b =
      18.1362(8) A, c = 8.5631(4) A, beta = 102.735(10) degrees, V = 1367.56(11) A(3),
      Z = 4, R(1) = 0.0229, wR(2) = 0.0599 [1782 observed reflections with I >
      2sigma(I)]; II, triclinic, space group P(-)1 (no. 2), M = 454.5, a = 8.6222(9) A,
      b = 9.5683(10) A, c = 9.5712(10) A, alpha = 109.388(2) degrees, beta = 98.508(10)
      degrees, gamma = 102.361(12) degrees, V = 706.73(13) A(3), Z = 2, R(1) = 0.0446,
      wR(2) = 0.115 [1730 observed reflections with I > 2sigma(I)].

PMID- 12184768
TI  - A family of vanadate esters of monoionized and diionized aromatic 1,2-diols:
      synthesis, structure, and redox activity.
AB  - The concerned diols (general abbreviation, H(2)L) are catechol (H(2)L(1)) and its
      3,5-Bu(t)(2) derivative (H(2)L(2)). Esters of the type VO(xsal)(HL), 2, are
      obtained by reacting H(2)L with VO(xsal)(H(2)O) or VO(xsal)(OMe)(HOMe), where
      xsal(2-) is the diionized salicylaldimine of glycine (x = g), L-alanine (x = a),
      or L-valine (x = v). The reaction of VO(acac)(2) with H(2)L and the
      salicylaldimine (Hpsal) of 2-picolylamine has furnished VO(psal)(L), 3. In the
      structures of VO(gsal)(HL(1)), 2a, and VO(vsal)(HL(2)), 2f, the HL(-) ligand is
      O,O-chelated, the phenolic oxygen lying trans to the oxo oxygen atom. The xsal(2
      ) coligand has a folded structure and the conformation of 2f is exclusively endo.
      In both 2a and 2f the phenolic oxygen atom is strongly hydrogen bonded (O...O,
      2.60 A) to a carboxylic oxygen atom of a neighboring molecule. In
      VO(psal)(L(2)).H(2)O, 3b, the diionized diol is O,O-chelated to the metal and the
      water molecule is hydrogen bonded to a phenoxidic oxygen atom (O.O, 2.84 A). The
      C-O and C-C distances in the V(diol) fragment reveal that 2 is a pure catecholate
      and 3 is a catecholate-semiquinonate hybrid. In solution each ester gives rise to
      a single (51)V NMR signal (no diastereoisomers), which generally shifts downfield
      with a decrease in the ester LMCT band energy. The V(V)/V(IV) and catecholate
      semiquinonate reduction potentials lie near -0.75 and 0.35, and 1.10 and 0.70 V
      vs SCE for 2 and 3, respectively. Molecular oxygen reacts smoothly with 2
      quantitatively furnishing the corresponding o-quinone, and in the presence of
      H(2)L the reaction becomes catalytic. In contrast, type 3 esters are inert to
      oxygen. The initial binding of O(2) to 2 is proposed to occur via hydrogen
      bonding with chelated HL(-).

PMID- 12184769
TI  - Reactions of a ruthenium(II) arene antitumor complex with cysteine and
      methionine.
AB  - The Ru(II) organometallic antitumor complex [(eta(6)-biphenyl)RuCl(en)][PF(6)]
      (1) reacts slowly with the amino acid L-cysteine (L-CysH(2)) in aqueous solution
      at 310 K. Reactions were followed over periods of up to 48 h using HPLC,
      electronic absorption spectroscopy, LC-ESI-MS, and 1D or 2D (1)H and (15)N NMR
      spectroscopy. Reactions at a 1 mM/2 mM (Ru/L-CysH(2)) ratio were multiphasic in
      acidic solutions (pH 5.1) and appeared to involve aquation as the first step.
      Initially, 1:1 adducts involving substitution of Cl by S-bound or O-bound L
      CysH(2), [(eta(6)-biphenyl)Ru(S-L-CysH)(en)](+) (4a) and [(eta(6)-biphenyl)Ru(O-L
      CysH(2))(en)](2+) (4b) formed, followed by the cystine adduct [(eta(6)
      biphenyl)Ru(O-Cys(2)H(2))(en)](2+) (3), and two dinuclear complexes from which
      half or all of the chelated ethylenediamine had been displaced, [(eta(6)
      biphenyl)Ru(H(2)O)(microS,N-L-Cys)Ru(eta(6)-biphenyl)(en)](2+) (5) containing one
      bridging cysteine, and [(eta(6)-biphenyl)Ru(O,N-L-Cys-S)(S-L-Cys-N)Ru(eta(6)
      biphenyl)(H(2)O)] (6) containing two bridging cysteines. The unusual cluster
      species [(biphenyl)Ru](8) (7a) was also detected by MS and was more prevalent in
      reactions at higher L-CysH(2) concentrations. Complex 5 was the dominant product
      at pH 2-5, but overall, only ca. 50% of 1 reacted with L-CysH(2) in these
      conditions. The reaction between 1 and L-CysH(2) was suppressed in 50 mM
      triethylammonium acetate solution at pH > 5 or in 100 mM NaCl. Only 27% of
      complex 1 reacted with L-methionine (L-MetH) at an initial pH of 5.7 after 48 h
      at 310 K and gave rise to only one adduct [(eta(6)-biphenyl)Ru(S-L-MetH)(en)](2+)
      (8).

PMID- 12184770
TI  - Self-assembling vanadium oxide nanotubes by organic molecular templates.
AB  - Vanadium oxide nanotubes were synthesized as the main product by hydrothermal
      self-assembling from ammonium metavanadate (NH(4)VO(3)) and organic molecules as
      structure-directing templates. Several kinds of templates including primary
      amines (C(n)H(2n+1)NH(2)), alpha,omega-diamines (H(2)N[CH(2)](n)NH(2)), and
      quaternary ammonium salt (CTAB) were demonstrated to be appropriate for the
      formation of nanotubes. The morphologies and structures of the nanotubes were
      characterized by X-ray powder diffraction (XRD), transmission electron microscopy
      (TEM), high-resolution transmission electron microscopy (HRTEM), and thermal
      gravimetric analysis (TGA). The nanotubes were found forming together with the
      layered structures and the sheetlike structures. On the basis of the growth
      mechanism of WS(2) nanotubes proposed by our group, a possible rolling mechanism
      was proposed, which might be a suitable general formation mechanism for types of
      nanotubes from lamellar structures.

PMID- 12184771
TI  - Chromium complexes of an isomeric N-donor ligand, 2-[(N
      arylamino)phenylazo]pyridine: amination reactions, X-ray structure, and redox
      properties.
AB  - The chromium chemistry of two positional isomers of the ligand 2-[(N
      arylamino)phenylazo]pyridine (HL(1)and HL(2)) are described. While the ligand
      HL(1) coordinates as a bischelating tridentate N,N,N-donor, [L(1)](-), with
      deprotonation of the amine nitrogen, its isomer HL(2) coordinates as a neutral
      bidentate N,N-donor. The amine nitrogen in this case remains protonated. Thus the
      reaction of CrCl(3).nH(2)O with HL(1) produced the brown cationic complex,
      [Cr(L(1))(2)](+), [1](+). The representative X-ray structure of [1a](ClO(4)) is
      reported. The two azo nitrogens of the anioinc tridentate ligand approach the
      metal center closest with Cr(1)-N(azo) av 1.862(6) A. There is a significant
      degree of ligand backbone conjugation in the coordinated ligands, which resulted
      in shortening of the C-N distances and also in lengthening of the diazo (N=N)
      distances. Two synthetic approaches for the synthesis of chromium complexes of
      HL(2) are investigated. The first approach is based on the substitution reaction,
      wherein all the coordinated CO ligands of Cr(CO)(6) were completely substituted
      by the three bidentate HL(2) ligands to produce a violet complex [Cr(HL(2))(3)].
      The second approach is based on para-amination reaction of coordinated 2
      (phenylazo)pyridine (pap). Thus the reaction of an inert complex,
      [CrCl(2)(pap)(2)], with ArNH(2) yields a mixed ligand complex,
      [CrCl(2)(pap)(HL(2))], 3. In this reaction one of the two coordinated pap ligands
      in [CrCl(2)(pap)(2)] undergoes amination at the para carbon (with respect to the
      diazo function) to yield HL(2) in situ. This metal-promoted transformation is
      authenticated by the X-ray structure determination of a representative complex,
      [CrCl(2)(pap)(HL(2a))], 3a. Notable differences in bond distances along the
      ligand backbones of the two coordinated ligands in 3a indicate different levels
      of metal-ligand overlap in this complex. All the chromium complexes of HL(2) are
      characterized by their intense blue-violet color. The frequencies of the visible
      range transitions in these complexes linearly correlate with the Hammett's
      substitution constant. Intraligand charge-transfer transitions in the visible
      region are believed to be responsible for the intense color. Redox properties of
      all these complexes are reported.

PMID- 12184772
TI  - Cadmium cyclam complexes: interconversion of cis and trans configurations and
      fixation of CO(2).
AB  - There is current interest in the antiviral activity of metal, especially zinc,
      cyclam (1,4,8,11-tetraazacyclotetradecane) complexes. Their biological activity
      appears to be dependent on recognition of membrane proteins (viral coreceptors)
      and therefore on their configurations. Here, we use Cd(II) as a probe for Zn(II)
      on account of its useful NMR properties. We have prepared and characterized
      Cd(II) complexes of cyclam, Cd(cyclam)(ClO(4))(2) (1), Cd(cyclam)Cl(2) (2), and
      [Cd(3)(cyclam)(3)(CO(3))](ClO(4))(4).3H(2)O (3), and have identified key markers
      for various configurations adopted by these complexes under a variety of solution
      conditions using 1D and 2D (1)H, (13)C, (15)N, and (111)Cd NMR spectroscopy,
      including Karplus-type analyses of (1)H, (1)H and (1)H, (111)Cd coupling
      constants. These complexes were stable at high pH (>8.2) but dissociated
      completely on lowering the pH to 5.3. Two major configurations of both 1 and 2
      exist in aqueous solution: trans-I (R,S,R,S at nitrogen) and cis-V (R,R,R,R).
      (3)J((111)Cd, (1)H) coupling constants showed that the five-membered rings of the
      trans-I configuration adopt the eclipsed conformation, and the six-membered rings
      adopt chair conformations. The X-ray crystal structure of 3 shows that the cation
      adopts the unusual folded cis-I configuration in which all of the N-H bonds are
      oriented up (or down) in a novel tri-cadmium cluster. This complex contains
      triply bridged carbonate fixed from atmospheric CO(2). Each Cd(II) is bound by
      two cis oxygen atoms from CO(3)(2-) (Cd-O bond lengths 2.373 and 2.412 A) and
      four nitrogen atoms from cyclam (C-N bond lengths 2.270-2.323 A). The geometry
      can be described as trigonal bipyramidal with the two donor oxygen atoms
      occupying one of the apices of the in-plane triangle. In acetonitrile solution,
      complex 3 gives rise to only one configuration, trans-I, with eclipsed five
      membered rings, and six-membered rings with chair conformations.

PMID- 12184773
TI  - New alkyl-cobalt(III) complexes containing chiral centers in the chelating
      system.
AB  - The complex mer-[Co(III)(L(1)Npy)(2)](+) (1') where the L(1)Npy(-) is the
      tridentate 3-[(2-pyridyl)methylimino]butan-2-one oximate ligand, gives alkyl
      cobalt derivatives after reduction with NaBH(4)/Pd(2+) to the Co(I) and
      alkylation. The formation of the cobalt-carbon bond is accompanied by the
      reduction to the amino form of one or both imino ligands (depending on the
      experimental conditions) initially present in 1'. In one series of experiments,
      complexes of the type fac-[RCo(III)(L(1)Npy)(H-L(1)NHpy)](+) (R = Me, i-Pr,
      CH(2)Cl, CH(2)Br, CH(2)CF(3), and Bz) were obtained, in which only one of the two
      ligands was reduced to the amino form (H-L(1)NHpy). The saturation of one
      azomethine group causes the products to assume a fac configuration and induces
      the formation of one asymmetric carbon and one asymmetric nitrogen center in the
      chelating system. When an excess of reducing agent is used, both azomethine
      groups may be saturated, causing the introduction of one pair of chiral carbons
      and one pair of chiral nitrogens. Two isomers of the methyl derivative
      [MeCo(III)(L(1)NHpy)(H-L(1)NHpy)](+) were isolated. The X-ray analysis reveals
      that these isomers differ from one another in configuration of the C and N chiral
      centers. Possible reaction mechanisms leading to these different types of
      complexes are proposed.

PMID- 12184774
TI  - Octahedral-tetrahedral equilibrium and solvent exchange of cobalt(II) ions in
      primary alkylamines.
AB  - The enthalpy differences (Delta H degrees ) of the equilibrium between the
      octahedral and tetrahedral solvated cobalt(II) complexes were obtained in some
      primary alkylamines such as propylamine (pa, 36.1 +/- 2.3 kJ mol(-1)), n
      hexylamine (ha, 34.9 +/- 1.0 kJ mol(-1)), 2-methoxyethylamine (meea, 44.8 +/- 3.1
      kJ mol(-1)), and benzylamine (ba, 50.1 +/- 3.6 kJ mol(-1)) by the
      spectrophotometric method. The differences in the energy levels between the two
      geometries of the cobalt(II) complexes in the spherically symmetric field (Delta
      E(spher)) were estimated from the values of Delta H degrees by offsetting the
      ligand field stabilization energies. It was indicated that the value of Delta
      E(spher) is the decisive factor in determining the value of Delta H degrees and
      is largely dependent on the electronic repulsion between the d-electrons and the
      donor atoms and the interelectronic repulsion in the d orbitals. The comparison
      between activation enthalpies (Delta H(++)) for the solvent exchange reactions of
      octahedral cobalt(II) ions in pa and meea revealed that the unexpectedly large
      rate constant and small Delta H(++) in pa are attributed to the strong electronic
      repulsion in the ground state and removal of the electronic repulsion in the
      dissociative transition state, which can give the small Delta E(spher) between
      the ground and transition states. Differences in the solvent exchange rates and
      the DeltaH(++) values of the octahedral metal(II) ions in some other solvents are
      discussed in connection with the electronic repulsive factors.

PMID- 12184775
TI  - Growth of compound Bi(III)- VI(A)-VII(A) crystals with special morphologies under
      mild conditions.
AB  - A series of crystals Bi(III)-VI(A)-VII(A), including the platelike crystals
      BiOCl, polygonal tubular crystals BiSCl, bundle-rodlike crystals
      Bi(19)S(27)Br(3), and BiSI, have been grown with use of mild solution routes in
      an ethanol system. The products are characterized by means of X-ray powder
      diffraction (XRD), electron diffraction (ED), scanning electronic microscopy
      (SEM), and Raman spectrum techniques. A possible mechanism of the reaction and of
      the growth of the crystals is proposed.

PMID- 12184776
TI  - Solution and solid-state structure of the anion [Ag(2)[closo-CB(11)H(12)](4)](2
      ).
AB  - Addition of the carbene 1,3-dimesitylimidazol-2-ylidene (IMes) to a toluene
      solution of Ag[closo-CB(11)H(12)] results in the formation of the complex
      [(IMes)(2)Ag](2)[Ag(2)[closo-CB(11)H(12)](4)], the anionic component of which
      contains two silver(I) centers bridged by two carboranes in addition to one
      terminally bound carborane on each metal, in the solid-state. Comparison of the
      observed (11)B[(1)H] NMR chemical shifts of [(IMes)(2)Ag](2)[Ag(2)[closo
      CB(11)H(12)](4)] or Ag[closo-CB(11)H(12)] with [NBu(4)][closo-CB(11)H(12)] in
      CD(2)Cl(2) demonstrates that the silver ion interacts significantly with the cage
      in solution. Theoretical investigations using the ab initio/GIAO/NMR method of
      [closo-CB(11)H(12)](-) and Na[closo-CB(11)H(12)] as model geometries for the
      silver salts support experimental evidence for these Ag...[BH] interactions in
      solution.

PMID- 12184777
TI  - The structure of 1-thia-closo-decaborane(9), 1-SB(9)H(9), as determined by
      microwave spectroscopy and quantum chemical calculations.
AB  - The microwave spectrum of 1-thia-closo-decaborane(9), 1-SB(9)H(9), has been
      investigated in the 12-61 GHz spectral region. The molecule has C(4v) symmetry.
      The spectra of five isotopomers have been assigned, and a precise substitution
      structure of the non-hydrogen atoms has been determined. It was found that the
      axial sulfur atom causes a substantial expansion of the B(4) belt adjacent to
      sulfur and hence leads to a significant distortion from a regular bicapped square
      antiprismatic structure. The experimental work has been supplemented by high
      level ab initio (MP2/6-311G**) and density functional theory calculations
      (B3LYP/6-311G** and B3LYP/cc-pVTZ). The agreement between the substitution
      structure and the two DFT calculations is very good in each case. The agreement
      is considerably poorer for the MP2/6-311G** calculations, particularly for the
      sulfur-boron bond length.

PMID- 12184778
TI  - Dinuclear gold(I) dithiophosphonate complexes: synthesis, luminescent properties,
      and X-ray crystal structures of [AuS(2)PR(OR')](2) (R = Ph, R' = C(5)H(9); R = 4
      C(6)H(4)OMe, R' = (1S,5R,2S)-(--)-menthyl; R = Fc, R' =
      (CH(2))(2)O(CH(2))(2)OMe).
AB  - 2,4-Diaryl- and 2,4-diferrocenyl-1,3-dithiadiphosphetane disulfide dimers
      (RP(S)S)(2) (R = Ph (1a), 4-C(6)H(4)OMe (1b), FeC(10)H(9) (Fc) (1c)) react with a
      variety of alcohols, silanols, and trialkylsilyl alcohols to form new
      dithiophosphonic acids in a facile manner. Their corresponding salts react with
      chlorogold(I) complexes in THF to produce dinuclear gold(I) dithiophosphonate
      complexes of the type [AuS(2)PR(OR')](2) in satisfactory yield. The asymmetrical
      nature of the ligands allows for the gold complexes to form two isomers (cis and
      trans) as verified by solution (1)H and (31)P[(1)H] NMR studies. The X-ray
      crystal structures of [AuS(2)PR(OR')](2) (R = Ph, R' = C(5)H(9) (2); R = 4
      C(6)H(4)OMe, R' = (1S,5R,2S)-(-)-menthyl (3); R = Fc, R' =
      (CH(2))(2)O(CH(2))(2)OMe (4)) have been determined. In all cases only the trans
      isomer is obtained, consistent with solid state (31)P NMR data obtained for the
      bulk powder of 3. Crystallographic data for 2 (213 K): orthorhombic, Ibam, a =
      12.434(5) A, b = 19.029(9) A, c = 11.760(4) A, V = 2782(2) A(3), Z = 4. Data for
      3 (293 K): monoclinic, P2(1), a = 7.288(2) A, b = 12.676(3) A, c = 21.826(4) A,
      beta = 92.04(3) degrees, V = 2015.0(7) A(3), Z = 2. Data for 4 (213 K):
      monoclinic, P2(1)/n, a = 11.8564(7) A, b = 22.483(1) A, c = 27.840(2) A, beta =
      91.121(1) degrees, V = 7419.8(8) A(3), Z = 8. Moreover, 1a-c react with
      [Au(2)(dppm)Cl(2)] to form new heterobridged trithiophosphonate complexes of the
      type [Au(2)(dppm)(S(2)P(S)R)] (R = Fc (12)). The luminescence properties of
      several structurally characterized complexes have been investigated. Each of the
      title compounds luminesces at 77 K. The results indicate that the nature of
      Au...Au interactions in the solid state has a profound influence on the optical
      properties of these complexes.

PMID- 12184779
TI  - Supramolecular gold(I) thiobarbiturate chemistry: combining aurophilicity and
      hydrogen bonding to make polymers, sheets, and networks.
AB  - The cooperative forces of aurophilic and hydrogen bonding have been used in the
      self-assembly of phosphine or diphosphine complexes of gold(I) with the thiolate
      ligands derived from 2-thiobarbituric acid, SC(4)H(4)N(2)O(2), by single or
      double deprotonation. The reaction of the corresponding gold(I) trifluoroacetate
      complex with SC(4)H(4)N(2)O(2) gave the complexes
      [Au(SC(4)H(3)N(2)O(2))(PPh(3))], 1, [(AuSC(4)H(3)N(2)O(2))(2)(micro-LL)], with LL
      = Ph(2)PCH(2)PPh(2), 2a, Ph(2)P(CH(2))(3)PPh(2), 2b, or Ph(2)PCH=CHPPh(2), 2c, or
      the cyclic complex [Au(2)(micro-SC(4)H(2)N(2)O(2))(micro
      Ph(2)PCH(2)CH(2)PPh(2))], 3. In the case with LL = Ph(2)P(CH(2))(6)PPh(2), the
      reaction led to loss of the diphosphine ligand to give
      [Au(6)(SC(4)H(3)N(2)O(2))(6)], 4, a hexagold(I) cluster complex in which each
      gold(I) center has trigonal AuS(2)N coordination. Structure determinations show
      that 1 has no aurophilic bonding, 2b, 3, and 4 have intramolecular aurophilic
      bonding, and 2c has intermolecular aurophilic bonding that contributes to the
      supramolecular structure. All the complexes undergo supramolecular association
      through strong NH...O and/or OH...N hydrogen bonding, and complex 3 also takes
      part in CH...O hydrogen bonding. The supramolecular association leads to
      formation of interesting polymer, sheet, or network structures, and 4 has a
      highly porous and stable lattice structure.

PMID- 12184781
TI  - Chemistry of some amino acid complexes of ruthenium. Synthesis, characterization,
      and DNA binding properties.

PMID- 12184780
TI  - Flexible square supramolecular rings with hydrogen-bonded bushing in solid-state
      oxalurate complexes: versatility of the oxalurate ligand in covalent and
      noncovalent binding.
AB  - Isotypic pseudooctahedral complexes of Co, Ni, and Cu with two chelating
      oxalurate ligands and two water molecules, trans-[M(oxalurate)(2)(H(2)O)(2)],
      have been synthesized and isolated by a novel progressive crystallization
      technique. Diffraction analyses reveal that the three complexes form isotypic
      solid-state structures in which the molecular connectivity and complex network of
      noncovalent interactions are qualitatively identical throughout the series. The
      oxalurate groups form unbounded chains through two different self-recognition
      patterns-a typical DA-AD motif and an unusual DDA'-A'DD form (D = hydrogen bond
      donor, A' = double acceptor). The unsymmetrical oxalurate group possesses the
      topological properties necessary to form aggregates of higher symmetry, and the
      "M(oxalurate)(2)" fragments form a rhombic 2-D motif with hydrogen-bonded corners
      and with hydrogen-bond acceptors directed to the inside of the cyclic aggregate.
      The 2-D net is stacked to form a channeled 3-D structure, in which the
      coordinated aqua ligands form the principal interlayer interactions. The slanted
      channels are occupied by the axial waters and by waters of crystallization, which
      are hydrogen bonded to the channel walls to form an ordered bushing. The
      extensive 3-D hydrogen-bonded superstructure is flexible enough to accommodate
      the distortion produced by the Jahn-Teller effect in the copper compound without
      requiring a qualitative structural change. The bonds affected by Jahn-Teller
      distortion in the Cu complex [Cu-O = 2.3788(15) A] are significantly longer than
      their analogues in the Co and Ni complexes [Co-O = 2.175(2), Ni-O = 2.094(9) A].

PMID- 12184783
TI  - Substrate recognition by a family of uracil-DNA glycosylases: UNG, MUG, and TDG.
AB  - In response to continuous hydrolytic and oxidative DNA damage, cells of all
      organisms have a complex network of repair systems that recognize, remove, and
      rebuild the injured sites. Damaged pyrimidines are generally removed by
      glycosylases that must scan the entire genome to locate lesions with sufficient
      fidelity to selectively remove the damage without inadvertent removal of normal
      bases. We report here studies conducted with a series of base analogues designed
      to test mechanisms of base recognition suggested by structural studies of
      glycosylase complexes. The oligonucleotide series examined here includes 5
      halouracils with increasing substituent size and purine analogues placed opposite
      the target uracil with hydrogen, amino, and keto substituents in the 2- and 6
      positions. The glycosylases studied here include Escherichia coli uracil-DNA
      glycosylase (UNG), E. coli mismatch uracil-DNA glycosylase (MUG), and the
      Methanobacterium thermoautotrophicum mismatch thymine-DNA glycosylase (TDG). The
      results of this study suggest that these glycosylases utilize several strategies
      for base identification, including (1) steric limitations on the size of the 5
      substituent, (2) electronic-inductive properties of the 5-substituent, (3)
      reduced thermal stability of mispairs, and (4) specific functional groups on the
      purine base in the opposing strand. Contrary to predictions based upon the
      crystal structure, the preference of MUG for mispaired uracil over thymine is not
      based upon steric exclusion. Furthermore, the preference for mispaired uracil
      over uracil paired with adenine is more likely due to reduced thermal stability
      as opposed to specific recognition of the mispaired guanine. On the other hand,
      TDG, which exhibits modest discrimination among various pyrimidines, shows strong
      interactions with functional groups present on the purine opposite the target
      pyrimidine. These results provide new insights into the mechanisms of base
      selection by DNA repair glycosylases.

PMID- 12184784
TI  - Characterization of hard metal dusts from sintering and detonation coating
      processes and comparative hydroxyl radical production.
AB  - Dust samples from sintering and detonation coating hard-metal processes were
      characterized, compared, and contrasted for morphology, composition, and
      generation of hydroxyl radicals. Inhalation of respirable hard-metal (sintered
      carbide) dusts from hard-metal processes is known to cause fibrotic and asthmatic
      lung disease. Scanning electron microscopy/energy-dispersive X-ray analysis was
      used for morphology, composition, and elemental distribution. An electron spin
      resonance (ESR) spin trapping technique was used to detect hydroxyl radical
      generation. Samples were incubated with air-saturated buffer solutions containing
      a spin trap and analyzed by ESR for the presence of *OH in solution.
      Postdetonation coating samples often had surface contamination of Co on the WC
      particles, as shown by elemental mapping of individual particles; this was not
      evident in predetonation samples or unsintered materials in this study. ESR
      measurements show that both detonation-gun materials were capable of generating
      *OH , while the WC, cobalt, and presintered mixture did not produce detectable
      amounts of *OH radicals. The DMPO/*OH adduct formation was apparently facilitated
      by Fe-mediated reactions for predetonation dusts, and by Fe-mediated site
      specific reactions for postdetonation dusts. The overspray materials from the
      detonation-gun process produced 9-fold more *OH radicals than the predetonation
      coating mixture. Overall, this study indicates there are substantial differences
      between postdetonation materials and both predetonation and unsintered hard-metal
      process materials with respect to morphology, elemental distribution, and *OH
      radical generation reactions and that these differences may be important in the
      toxic potential of those materials.

PMID- 12184785
TI  - Site-specific hydroxylation at polyguanosine in double-stranded DNA by nickel(II)
      in the presence of SH compounds: comparison with singlet oxygen-induced DNA
      damage.
AB  - We examined the mechanism of DNA damage induced by carcinogenic Ni(II) in the
      presence of SH compounds. In the presence of model endogenous SH compounds,
      dithiothreitol (DTT), 1,4-dithio-L-threitol, and dithioerythritol, Ni(II) induced
      damage to (32)P-5'-end-labeled DNA fragments obtained from the human c-Ha-ras-1
      protooncogene and the p53 tumor suppressor gene. The intensity of Ni(II)-mediated
      DNA damage induced by DTT was stronger than that by other model endogenous SH
      compounds, 1,4-dithio-L-threitol and dithioerythritol. DNA damage induced by
      Ni(II) plus DTT was observed only when the DNA was treated with piperidine,
      suggesting that Ni(II) plus DTT caused only base damage. Formamidopyrimidine-DNA
      glycosylase, which is known to recognize 8-oxodG as well as Fapy residues,
      treatment induced cleavage sites, mainly guanine residues, particularly at the 5'
      GG-3', 5'-GGG-3', and 5'-GGGG-3' sequences, in DNA incubated with Ni(II) in the
      presence of DTT. SOD and catalase inhibited the DNA damage, suggesting that DNA
      damage involved superoxide anion and hydrogen peroxide. Sodium azide, a potent
      and relatively specific scavenger of (1)O(2), inhibited DNA damage by Ni(II) in
      the presence of DTT, whereas the sequence specificity of DNA damage was different
      from that obtained by (1)O(2) generating agent. The formation of 8-oxodG in calf
      thymus DNA by Ni(II) was observed with the physiological thiols, dihydrolipoic
      acid and mercaptopyruvate, as well as with DTT. These results suggest that Ni(II)
      and DTT form a reactive species, which may be responsible for causing guanine
      specific DNA damage. Endogenous SH compounds, which have similar chemical
      structures to DTT, would participate in nickel carcinogenesis through causing
      oxidative DNA damage.

PMID- 12184786
TI  - First principles calculations of the tautomers and pK(a) values of 8-oxoguanine:
      implications for mutagenicity and repair.
AB  - 8-Oxoguanine is a mutagenic oxidative damage product of guanine that has been the
      subject of many experimental studies. Despite numerous references to this damaged
      base, its precise configuration or population of configurations in equilibrium
      are unknown, as it can be drawn in over 100 potential neutral and ionized
      tautomeric forms. The structural uncertainty surrounding 8-oxoguanine complicates
      mechanistic studies of its mutagenicity and capacity to be recognized for repair.
      Experimental measurements on the tautomeric equilibria and pK(a) values of 8
      oxoguanine are complicated by its insolubility in water. Therefore, we used first
      principles quantum mechanics (density functional theory, B3LYP, in combination
      with the Poisson-Boltzmann continuum-solvation model) to investigate the relative
      stabilities and site-specific pK(a) values of various neutral and ionized
      tautomers of 8-oxoguanine. We show that the major tautomer of neutral 8
      oxoguanine in aqueous solution is the 6,8-diketo form 2, and that 8-oxoguanine
      has increased acidity at N1 relative to guanine. Our calculations on 2'
      deoxyguanosine-3',5'-bisphosphate and its 8-oxo analogue support the accepted
      conclusion that repulsion between the O8 of 8-oxoguanine and O5' of the backbone
      sugar promote 8-oxoguanine:adenine pairings in the syn:anti conformation.
      Further, we show that the N7 proton of 8-oxoguanine is difficult to remove either
      through tautomerization or ionization, consistent with its involvement as an
      important landmark in distinguishing guanine from 8-oxoguanine. The possibility
      of additional structural landmarks that distinguish 8-oxoguanine from guanine,
      and a possible mechanism for glycosylase removal of 8-oxoguanine are discussed.

PMID- 12184787
TI  - Structure-activity relationship for the biotransformation of haloalkenes by rat
      liver microsomal glutathione transferase 1.
AB  - Many haloalkenes are nephrotoxic in rodents, and experimental evidence supports a
      glutathione-dependent bioactivation pathway that leads to nephrotoxicity or
      nephrocarcinogenicity, or both. The reaction of glutathione with haloalkenes is
      catalyzed by cytosolic glutathione transferases (cGST) and microsomal glutathione
      transferase 1 (MGST1). The aim of this study was to develop a computational
      approach to predict the competency of cGST and MGST1 to catalyze the reaction of
      glutathione with a range of haloalkenes. The hypothesis tested was that the
      semiempirically computed energy of the lowest unoccupied molecular orbital
      (E(LUMO)) of a haloalkene may be used to predict the competency of cGST and MGST1
      to catalyze its reaction with glutathione. The MGST1- and cGST-catalyzed reaction
      of glutathione with nine haloalkenes with E(LUMO) values ranging from -1.14 to
      0.38 eV was determined experimentally. The data indicated that the E(LUMO) values
      for haloalkenes were inversely related to the specific activity of the MGST1
      catalyzed reaction but not the cGST-catalyzed reaction. These data also
      demonstrated that MGST1 catalyzed the reaction of glutathione with haloalkenes
      with E(LUMO) values equal to or more negative than -0.73 eV and that cGST
      catalyzed the reaction of glutathione with haloalkenes with E(LUMO) values more
      negative than -0.06 eV.

PMID- 12184788
TI  - Identification and characterization of methylated and ring-fission metabolites of
      tea catechins formed in humans, mice, and rats.
AB  - (-)-Epigallocatechin gallate (EGCG), the most abundant tea catechin, has been
      proposed to be beneficial to human health based on its strong antioxidative and
      other biological activities in vitro. Inadequate knowledge regarding the
      bioavailability and biotransformation of EGCG in humans, however, has limited our
      understanding of its possible beneficial health effects. In this study, 4',4' '
      di-O-methyl-EGCG (4',4' '-DiMeEGCG) was detected in human plasma and urine by
      LC/MS/MS following green tea ingestion. Both 4',4' '-DiMeEGCG and EGCG reached
      peak plasma values (20.5 +/- 7.7 and 145.4 +/- 31.6 nM, respectively, in 4
      subjects) at 2 h after the dose. The half-lives of 4',4' '-DiMeEGCG and EGCG were
      4.1 +/- 0.8 and 2.7 +/- 0.9 h, respectively. The cumulative urinary excretion of
      4',4' '-DiMeEGCG during a 24 h period was 140.3 +/- 48.6 microg, about 5-fold
      higher than that of EGCG, but the excreted 4',4' '-DiMeEGCG and EGCG in urine
      only accounted for about 0.1% of ingested EGCG. (-)-5-(3',4',5'-Trihydroxyphenyl)
      gamma-valerolactone (M4) and (-)-5-(3',4'-dihydroxyphenyl)-gamma-valerolactone
      (M6), along with another possible ring-fission metabolite, (-)-5-(3',5'
      dihydroxyphenyl)-gamma-valerolactone (M6'), were detected in human urine after
      green tea ingestion. The cumulative excretion of M4, M6', and M6 during a 24 h
      period ranged from 75 microg to 1.2 mg, 0.6 to 6 mg, and 0.6 to 10 mg,
      respectively. The combined excretion of all three ring-fission metabolites
      accounted for 1.5-16% of ingested catechins. M4, M6', and M6 were all observed
      after the ingestion of pure EGCG or EGC by human subjects, whereas only M6 was
      produced after EC ingestion. These metabolites as well as monomethylated EGCG
      were detected in mice and rats after tea or EGCG administration, and the tissue
      levels reflected the rather low bioavailability of EGCG in rats. The presently
      characterized methylated EGCG metabolites and ring-fission products exist in
      substantial quantities and may contribute to the biological activities of tea.

PMID- 12184789
TI  - Oxidative bioactivation of crotyl alcohol to the toxic endogenous aldehyde
      crotonaldehyde: association of protein carbonylation with toxicity in mouse
      hepatocytes.
AB  - Recent confirmation that the toxic unsaturated aldehyde crotonaldehyde (CA)
      contributes to protein damage during lipid peroxidation confers interest on the
      molecular actions of this substance. However, since a plethora of structurally
      related aldehydes form during membrane oxidation, clarifying the toxicological
      significance of individual products (e.g., CA) is challenging. To facilitate
      study of the mechanisms underlying CA toxicity, we explored the possibility that
      it can be formed enzymatically from an unsaturated precursor, crotyl alcohol.
      This is analogous to the way allyl alcohol is converted in vivo to its toxic
      oxidation product, acrolein. In kinetic studies, we found that crotyl alcohol was
      readily oxidized by equine liver alcohol dehydrogenase, with electrospray-mass
      spectrometry confirming that CA was the main product formed. Moreover, in mouse
      hepatocytes, crotyl alcohol produced marked time- and concentration-dependent
      cell killing as well as pronounced glutathione depletion. Both cytotoxicity and
      glutathione loss were abolished by the alcohol dehydrogenase inhibitor 4
      methylpyrazole, indicating an oxidation product mediated these effects. In
      keeping with expectations that carbonyl-retaining Michael addition adducts would
      feature prominently during protein modification by CA, exposure to crotyl alcohol
      resulted in marked carbonylation of a wide range of cell proteins, an effect that
      was also abolished by 4-methylpyrazole. Damage to a subset of small proteins
      (e.g., 29, 32, 33 kDa) closely correlated with the severity of cell death.
      Collectively, these results demonstrate that crotyl alcohol is a useful tool for
      studying the biochemical and molecular events accompanying intracellular CA
      formation.

PMID- 12184790
TI  - Nitrosation and nitration of 2-amino-3-methylimidazo[4,5-f]quinoline by reactive
      nitrogen oxygen species.
AB  - Both cooked red meat intake and chronic inflammation/infection are thought to
      play a role in the etiology of colon cancer. The heterocyclic amine 2-amino-3
      methylimidazo[4,5-f ]quinoline (IQ) is formed during cooking of red meat and may
      be involved in initiation of colon cancer. Reactive nitrogen oxygen species
      (RNOS), components of the inflammatory response, contribute to the deleterious
      effects attributed to inflammation on normal tissues. This study assessed the
      possible chemical transformation of IQ by RNOS. RNOS were generated by various
      conditions to react with (14)C-IQ, and samples were evaluated by HPLC.
      Myeloperoxidase (MPO)-catalyzed reaction was dependent upon both H(2)O(2) and
      NO(2)(-). This reaction produced an azo-IQ dimer and IQ dimer along with two
      nitrated IQ products identified by ESI/MS. 2-Nitro-IQ was not detected. Product
      formation was inhibited by 2 mM cyanide. Reduction in nitrated products observed
      with 100 mM chloride was not altered with 0.5 mM taurine. Nitrated products were
      also produced by other conditions, ONOO(-) and NO(2)(-) + HOCl, which generate
      nitrogen dioxide radical. In contrast, conditions which generate N(2)O(3), such
      as diethylamine NONOate, produced only small amounts of nitrated products with
      the major product identified by MS and NMR as N-nitroso-IQ. MPO activation of IQ
      to bind DNA was dependent upon both H(2)O(2) and NO(2)(-). RNOS generated by
      ONOO(-) and DEA NONOate also activated IQ DNA binding. The nitrated IQ products
      were not activated by MPO to bind DNA. In contrast, N-nitroso-IQ was activated to
      bind DNA by MPO +/- NO(2)(-). HOCl activated N-nitroso-IQ, but not IQ. RAW cells
      produced N-nitroso-IQ and increased amounts of NO(2)(-)/NO(3)(-), when incubated
      with 0.1 mM IQ and stimulated with lipopolysaccharide and interferon gamma.
      Results demonstrate chemical transformation and activation of IQ by RNOS and
      activation of its N-nitroso product by biological oxidants, events which may
      contribute to initiation of colon cancer.

PMID- 12184791
TI  - Benzo[a]pyrene and benz[c]phenanthrene: the effect of structure on the binding of
      water molecules to the diol epoxides.
AB  - The interactions with water of the diol epoxides (DEs) of both a planar and a
      nonplanar PAH have been examined using molecular dynamics. To determine probable
      water locations around the DE for later use in the study of DE protonation,
      molecular dynamics simulations using the OPLS force field were carried out on
      diol epoxides surrounded by a 22 A box of explicit water molecules. Results for
      30 ps simulations indicate that 10-60% of the time, depending strongly on the
      conformation and type of the DE, there is a water molecule forming a hydrogen
      bond with the epoxide oxygen. The patterns seen in the frequency at which a DE
      binds a water molecule reflect patterns seen in the relationship between the type
      of PAH DE and amount of DNA adduct formation. Examination of the orientations and
      arrangements of the water and DEs during the simulations showed that the bound
      waters existed in several preferred configurations which are also dependent upon
      the PAH DE geometry.

PMID- 12184792
TI  - Contribution of glutathione and metallothioneins to protection against copper
      toxicity and redox cycling: quantitative analysis using MT+/+ and MT-/- mouse
      lung fibroblast cells.
AB  - Glutathione (GSH) and metallothioneins (MT) are believed to play important roles
      in protecting cells against high copper (Cu) concentrations. Little is known,
      however, about their specific intracellular interactions and the coordination of
      protective functions. We investigated contributions of GSH and MT to protection
      against Cu toxicity in fibroblasts derived from wild-type (MT+/+) and knockout
      (MT-/-) mice that were challenged with cupric nitrilotriacetate (Cu-NTA).
      Endogenous levels of GSH and MT were manipulated using an inhibitor of gamma
      glutamylcysteine synthetase, buthionine sulfoximine (BSO, 5 microM), as GSH
      depletor and ZnCl(2) (100 microM) as inducer of MT expression. BSO pretreatment
      markedly decreased cellular GSH levels in MT+/+ and MT-/- cells, by 65% and 70%,
      respectively, which resulted in Cu cytotoxicity accompanied by its elevated redox
      cycling activity and enhanced Cu-induced membrane phospholipid peroxidation. BSO
      pretreated MT-/- cells were markedly more sensitive to Cu despite the fact that
      the residual levels of GSH were similar in both BSO-pretreated MT+/+ and MT-/-
      cells. Zn pretreatment resulted in more than 10-fold induction of MT in MT+/+
      cells but not in MT-/- cells. Accordingly, Zn pretreatment afforded significant
      protection of MT+/+ cells against Cu cytotoxicity, likely associated with MT
      dependent suppression of Cu redox-cycling activity and phospholipid peroxidation,
      but it exerted no protection in MT-/- cells (as compared to naive cells). To
      determine whether MT functions specifically in Cu regulation or rather acts as a
      nonspecific Cu-binding cysteine-rich nucleophile, experiments were performed
      using MT+/+ and MT-/- cells pretreated with both BSO and Zn. BSO pretreatment did
      not affect Zn-induced MT expression in MT+/+ cells. As compared with BSO
      pretreatment alone, exposure to Cu of MT+/+ cells after Zn/BSO pretreatment
      resulted in the following: (i) a significantly higher viability; (ii) attenuated
      Cu-dependent redox-cycling activity; and (iii) a lower level of phospholipid
      peroxidation. In BSO/Zn-pretreated MT-/- cells, the redox-cycling activity of Cu
      and the level of phospholipid peroxidation remained remarkably higher than in
      naive cells and were not significantly different from those in cells pretreated
      with BSO alone. Cu-induced toxicity was remarkably higher in BSO/Zn-pretreated MT
      /- cells than in naive or Zn-pretreated cells, although slightly lower than in
      the MT-/- cells pretreated with BSO alone.

PMID- 12184793
TI  - Identification and characterization of (3",4"-dihydroxy)-1,N(2)-benzetheno-2'
      deoxyguanosine 3'-monophosphate, a novel DNA adduct formed by benzene
      metabolites.
AB  - Reaction of 2'-deoxyguanosine 3'-monophosphate with mixtures of the benzene
      metabolites p-benzoquinone (p-BQ) and hydroquinone (HQ) in an aqueous solution at
      pH 6.0 gave two main products which were isolated from the reaction mixture using
      reversed-phase HPLC and characterized using UV spectroscopy, negative ion
      electrospray mass spectrometry, and (1)H NMR. Variation of the ratio of p-BQ to
      HQ in the reaction mixture caused an increase in yield of one of the products.
      The two products were identified as (3"-hydroxy)-1,N(2)-benzetheno-2'
      deoxyguanosine 3'-monophosphate and a new product, not previously characterized,
      (3",4"-dihydroxy)-1,N(2)-benzetheno-2'-deoxyguanosine 3'-monophosphate. Similar
      products were isolated from identical reactions with 2'-deoxyguanosine. Reaction
      of calf thymus DNA with HQ and p-BQ (1:1, w/w) resulted in four main products as
      identified by (32)P-postlabeling coupled with HPLC. The relative abundances of
      these adducts were 9%, 60%, 27%, and 4%, respectively. Co-chromatography of (32)P
      postlabeled (3"-hydroxy)-1,N(2)-benzetheno-2'-deoxyguanosine 3'-monophosphate and
      (3",4"-dihydroxy)-1,N(2)-benzetheno-2'-deoxyguanosine 3'-monophosphate with the
      (32)P-postlabeled adducted calf thymus DNA identified these as the two minor
      products of the calf thymus DNA reaction.

PMID- 12184794
TI  - Tetrachloroethylene oxide: hydrolytic products and reactions with phosphate and
      lysine.
AB  - Tetrachloroethylene, or perchloroethylene (PCE), has considerable industrial use
      and is of toxicological interest because of a variety of effects. Most of the
      existing literature presents PCE oxide as a critical intermediate in the
      oxidative metabolism of PCE to Cl(3)CCO(2)H, oxalic acid, and products covalently
      bound to proteins, including trichloroacetyl derivatives of lysine. PCE oxide was
      synthesized by photochemical oxidation of PCE and characterized. Decomposition at
      neutral pH (t(1/2) = 7.9 min at 0 degrees C, 5.8 min at 23 degrees C, 2.6 min at
      37 degrees C) yielded only trace ( approximately 1%) Cl(3)CCO(2)H; the major
      products identified were CO (73% yield) and CO(2) (63% yield). In phosphate
      buffer (0.10 M) a major product was identified as oxalyl phosphate. Oxalyl
      chloride also reacted to form CO and CO(2) in aqueous solution and to form oxalyl
      phosphate in neutral phosphate buffer. Oxalyl phosphate decomposed to oxalic acid
      (t(1/2) = 53 min at 37 degrees C) but did not react with lysine. Reaction of PCE
      oxide with free lysine yielded the oxalic acid amide derivatives of lysine plus
      lysine dimers in which cross-linking of the amino groups involved oxalo linkage.
      The reaction of PCE oxide with albumin yielded mainly N(6)-oxalolysine and some
      (<5%) N(6)-trichloroacetyllysine. We propose a reaction pathway for PCE oxide
      based on our previous studies with trichloroethylene oxide, in which C-C bond
      scission is a major product of reaction in aqueous buffer and yields CO and
      CO(2). Oxalyl species are proposed as intermediates and prominent acylating
      species formed in the reactions of the epoxide. The formation of Cl(3)CCO(2)H in
      cytochrome P450 reactions is postulated to result from intramolecular migration
      within an enzyme intermediate.

PMID- 12184795
TI  - Lung toxicity and tumor promotion by hydroxylated derivatives of 2,6-di-tert
      butyl-4-methylphenol (BHT) and 2-tert-butyl-4-methyl-6-iso-propylphenol:
      correlation with quinone methide reactivity.
AB  - Acute pulmonary toxicity and tumor promotion by the food additive 2,6-di-tert
      butyl-4-methylphenol (BHT) in mice are well documented. These effects have been
      attributed to either of two quinone methides, 2,6-di-tert-butyl-4
      methylenecyclohexa-2,5-dienone (BHT-QM) formed through direct oxidation of BHT by
      pulmonary cytochrome P450 or a quinone methide formed by hydroxylation of a tert
      butyl group of BHT (to form BHTOH) followed by oxidation of this metabolite to
      BHTOH-QM. BHTOH-QM is a more reactive electrophile compared to BHT-QM due to
      intramolecular interactions of the side-chain hydroxyl with the carbonyl oxygen.
      To further examine this bioactivation pathway, an analogue of BHTOH was prepared,
      2-tert-butyl-6-(1'-hydroxy-1'-methyl)ethyl-4-methylphenol (BPPOH), that is
      structurally very similar to BHTOH but forms a quinone methide (BPPOH-QM) capable
      of more efficient intramolecular hydrogen bonding and, therefore, higher
      electrophilicity than BHTOH-QM. BPPOH-QM was synthesized and its reactivity with
      water, methanol, and glutathione determined to be >10-fold higher than that of
      BHTOH-QM. The conversions of BPPOH and BHTOH to quinone methides in lung
      microsomes from male BALB/cByJ mice were quantitatively similar, but in vivo the
      former was pneumotoxic at one-half of the dose required for the latter and one
      eighth of the dose required for BHT, as determined by increased lung weight:body
      weight ratios following a single i.p. injection. Similar differences were found
      in the doses of BHT, BHTOH, or BPPOH required for tumor promotion after a single
      initiating dose of 3-methylcholanthrene followed by three weekly injections of
      the phenol. The downregulaton of calpain II, previously shown to accompany lung
      tumor promotion by BHT and BHTOH, also occurred with BPPOH. The correlation
      between biologic activities of these phenols and the reactivities of their
      corresponding quinone methides provides additional support for the role of BHTOH
      QM as the principal metabolite responsible for the effects of BHT on mouse lung.

PMID- 12184796
TI  - Interaction of neuronal nitric oxide synthase with alpha1-adrenergic receptor
      subtypes in transfected HEK-293 cells.
AB  - BACKGROUND: The C-terminal four amino acids (GEEV) of human alpha1A-adrenergic
      receptors (ARs) have been reported to interact with the PDZ domain of neuronal
      nitric oxide synthase (nNOS) in a yeast two-hybrid system. The other two alpha1
      AR subtypes have no sequence homology in this region, raising the possibility of
      subtype-specific protein-protein interactions. RESULTS: We used co
      immunoprecipitation and functional approaches with epitope-tagged alpha1-ARs to
      examine this interaction and the importance of the C-terminal tail. Following co
      transfection of HEK-293 cells with hexahistidine/Flag (HF)-tagged alpha1A-ARs and
      nNOS, membranes were solubilized and immunoprecipitated with anti-FLAG affinity
      resin or anti-nNOS antibodies. Immunoprecipitation of HFalpha1A-ARs resulted in
      co-immunoprecipitation of nNOS and vice versa, confirming that these proteins
      interact. However, nNOS also co-immunoprecipitated with HFalpha1B- and HFalpha1D
      ARs, suggesting that the interaction is not specific to the alpha1A subtype. In
      addition, nNOS co-immunoprecipitated with each of the three HFalpha1-AR subtypes
      which had been C-terminally truncated, suggesting that this interaction does not
      require the C-tails; and with Flag-tagged beta1- and beta2-ARs. Treatment of PC12
      cells expressing HFalpha1A-ARs with an inhibitor of nitric oxide formation did
      not alter norepinephrine-mediated activation of mitogen activated protein
      kinases, suggesting nNOS is not involved in this response. CONCLUSIONS: These
      results show that nNOS does interact with full-length alpha1A-ARs, but that this
      interaction is not subtype-specific and does not require the C-terminal tail,
      raising questions about its functional significance.

PMID- 12184797
TI  - No place like Ome.
AB  - Of the two components of the word genome, 'ome' is the more interesting.

PMID- 12184798
TI  - Categorization of humans in biomedical research: genes, race and disease.
AB  - A debate has arisen regarding the validity of racial/ethnic categories for
      biomedical and genetic research. An epidemiologic perspective on the issue of
      human categorization in biomedical and genetic research strongly supports the
      continued use of self-identified race and ethnicity.

PMID- 12184799
TI  - Unraveling lipid metabolism with microarrays: effects of arachidonate and
      docosahexaenoate acid on murine hepatic and hippocampal gene expression.
AB  - The functions, actions, and regulation of polyunsaturated fatty acids (PUFAs) are
      beginning to be unraveled. Mice were fed diets rich in either arachidonic acid,
      docosahexaenoic acid, or both. Liver and hippocampus tissue were then analyzed
      through a combined gene expression-, lipid-, and behavioral- profiling strategy.
      Novel hippocampal PUFA-molecular targets suggest that PUFA transcriptionally
      regulated genes with roles in appetite and learning.

PMID- 12184800
TI  - Observation of intermittency in gene expression on cDNA microarrays.
AB  - We used scaled factorial moments to search for intermittency in the log
      expression ratios (LERs) for thousands of genes spotted on cDNA microarrays (gene
      chips). Results indicate varying levels of intermittency in gene expression. The
      observation of intermittency in the data analyzed provides a complimentary handle
      on moderately expressed genes, generally not tackled by conventional techniques.

PMID- 12184801
TI  - Towards understanding neural survival, differentiation and death.
AB  - A report from the 14th Biennial Meeting of the International Society for
      Developmental Neuroscience, Sydney, Australia, 31 January to 4 February 2002.

PMID- 12184802
TI  - Trends in genomic 'evo-devo'.
AB  - A report on the joint Spring meeting of the British Society of Developmental
      Biology and the Genetics Society, York, UK, 20-23 March 2002.

PMID- 12184803
TI  - Evolution of developmental mechanisms.
AB  - A report on the joint Spring meeting of the British Society of Developmental
      Biology and the Genetics Society, York, UK, 20-23 March 2002.

PMID- 12184804
TI  - Drosophila melanogaster, two years into the post-genomic era.
AB  - A report on the 43rd Drosophila Research Conference held in San Diego, USA, 10-14
      April 2002.

PMID- 12184805
TI  - The salmon genome (and other issues in bioinformatics).
AB  - A report on the fourth annual conference of the Society for Bioinformatics in the
      Nordic Countries (SOCBIN), Bioinformatics 2002, Bergen, Norway, 4-7 April 2002.

PMID- 12184806
TI  - Transcriptional programs activated by exposure of human prostate cancer cells to
      androgen.
AB  - BACKGROUND: Androgens are required for both normal prostate development and
      prostate carcinogenesis. We used DNA microarrays, representing approximately
      18,000 genes, to examine the temporal program of gene expression following
      treatment of the human prostate cancer cell line LNCaP with a synthetic androgen.
      RESULTS: We observed statistically significant changes in levels of transcripts
      of more than 500 genes. Many of these genes were previously reported androgen
      targets, but most were not previously known to be regulated by androgens. The
      androgen-induced expression programs in three additional androgen-responsive
      human prostate cancer cell lines, and in four androgen-independent subclones
      derived from LNCaP, shared many features with those observed in LNCaP, but some
      differences were observed. A remarkable fraction of the genes induced by androgen
      appeared to be related to production of seminal fluid and these genes included
      many with roles in protein folding, trafficking, and secretion. CONCLUSIONS:
      Prostate cancer cell lines retain features of androgen responsiveness that
      reflect normal prostatic physiology. These results provide a broad view of the
      effect of androgen signaling on the transcriptional program in these cancer
      cells, and a foundation for further studies of androgen action.

PMID- 12184807
TI  - Profound effect of normalization on detection of differentially expressed genes
      in oligonucleotide microarray data analysis.
AB  - BACKGROUND: Oligonucleotide microarrays measure the relative transcript abundance
      of thousands of mRNAs in parallel. A large number of procedures for normalization
      and detection of differentially expressed genes have been proposed. However, the
      relative impact of these methods on the detection of differentially expressed
      genes remains to be determined. RESULTS: We have employed four different
      normalization methods and all possible combinations with three different
      statistical algorithms for detection of differentially expressed genes on a
      prototype dataset. The number of genes detected as differentially expressed
      differs by a factor of about three. Analysis of lists of genes detected as
      differentially expressed, and rank correlation coefficients for probability of
      differential expression shows that a high concordance between different methods
      can only be achieved by using the same normalization procedure. CONCLUSIONS:
      Normalization has a profound influence of detection of differentially expressed
      genes. This influence is higher than that of three subsequent statistical
      analysis procedures examined. Algorithms incorporating more array-derived
      information than gene-expression values alone are urgently needed.

PMID- 12184808
TI  - Accurate normalization of real-time quantitative RT-PCR data by geometric
      averaging of multiple internal control genes.
AB  - BACKGROUND: Gene-expression analysis is increasingly important in biological
      research, with real-time reverse transcription PCR (RT-PCR) becoming the method
      of choice for high-throughput and accurate expression profiling of selected
      genes. Given the increased sensitivity, reproducibility and large dynamic range
      of this methodology, the requirements for a proper internal control gene for
      normalization have become increasingly stringent. Although housekeeping gene
      expression has been reported to vary considerably, no systematic survey has
      properly determined the errors related to the common practice of using only one
      control gene, nor presented an adequate way of working around this problem.
      RESULTS: We outline a robust and innovative strategy to identify the most stably
      expressed control genes in a given set of tissues, and to determine the minimum
      number of genes required to calculate a reliable normalization factor. We have
      evaluated ten housekeeping genes from different abundance and functional classes
      in various human tissues, and demonstrated that the conventional use of a single
      gene for normalization leads to relatively large errors in a significant
      proportion of samples tested. The geometric mean of multiple carefully selected
      housekeeping genes was validated as an accurate normalization factor by analyzing
      publicly available microarray data. CONCLUSIONS: The normalization strategy
      presented here is a prerequisite for accurate RT-PCR expression profiling, which,
      among other things, opens up the possibility of studying the biological relevance
      of small expression differences.

PMID- 12184809
TI  - Gene-expression profiling of the response of peripheral blood mononuclear cells
      and melanoma metastases to systemic IL-2 administration.
AB  - BACKGROUND: Interleukin-2 (IL-2) has direct pluripotent effects on cells with
      immune and inflammatory function. Which of these effects has a critical role in
      mediating tumor regression remains enigmatic. In this study, we compared early
      changes in transcriptional profiles of circulating mononuclear cells with those
      occurring within the microenvironment of melanoma metastases following systemic
      IL-2 administration. RESULTS: The results suggest that the immediate effects of
      IL-2 administration on the tumor microenvironment is transcriptional activation
      of genes predominantly associated with monocyte cell function; minimal effects
      were noted on migration, activation and proliferation of T cells. However,
      production of chemokines and markers of adhesion and migration within few hours
      of IL-2 administration may be responsible for a secondary recruitment of immune
      cells to the tumor site later. CONCLUSIONS: Our results suggest that IL-2 induces
      inflammation at tumor sites with three predominant secondary effects: activation
      of antigen-presenting monocytes; massive production of chemoattractants that may
      recruit other immune cells to the tumor (including MIG and PARC, which are
      specific for T cells); and activation of cytolytic mechanisms in monocytes
      (calgranulin, grancalcin) and NK cells (NKG5, NK4).

PMID- 12184810
TI  - A prediction-based resampling method for estimating the number of clusters in a
      dataset.
AB  - BACKGROUND: Microarray technology is increasingly being applied in biological and
      medical research to address a wide range of problems, such as the classification
      of tumors. An important statistical problem associated with tumor classification
      is the identification of new tumor classes using gene-expression profiles. Two
      essential aspects of this clustering problem are: to estimate the number of
      clusters, if any, in a dataset; and to allocate tumor samples to these clusters,
      and assess the confidence of cluster assignments for individual samples. Here we
      address the first of these problems. RESULTS: We have developed a new prediction
      based resampling method, Clest, to estimate the number of clusters in a dataset.
      The performance of the new and existing methods were compared using simulated
      data and gene-expression data from four recently published cancer microarray
      studies. Clest was generally found to be more accurate and robust than the six
      existing methods considered in the study. CONCLUSIONS: Focusing on prediction
      accuracy in conjunction with resampling produces accurate and robust estimates of
      the number of clusters.

PMID- 12184811
TI  - Normalization and analysis of DNA microarray data by self-consistency and local
      regression.
AB  - BACKGROUND: With the advent of DNA hybridization microarrays comes the remarkable
      ability, in principle, to simultaneously monitor the expression levels of
      thousands of genes. The quantitative comparison of two or more microarrays can
      reveal, for example, the distinct patterns of gene expression that define
      different cellular phenotypes or the genes induced in the cellular response to
      insult or changing environmental conditions. Normalization of the measured
      intensities is a prerequisite of such comparisons, and indeed, of any statistical
      analysis, yet insufficient attention has been paid to its systematic study. The
      most straightforward normalization techniques in use rest on the implicit
      assumption of linear response between true expression level and output intensity.
      We find that these assumptions are not generally met, and that these simple
      methods can be improved. RESULTS: We have developed a robust semi-parametric
      normalization technique based on the assumption that the large majority of genes
      will not have their relative expression levels changed from one treatment group
      to the next, and on the assumption that departures of the response from linearity
      are small and slowly varying. We use local regression to estimate the normalized
      expression levels as well as the expression level-dependent error variance.
      CONCLUSIONS: We illustrate the use of this technique in a comparison of the
      expression profiles of cultured rat mesothelioma cells under control and under
      treatment with potassium bromate, validated using quantitative PCR on a selected
      set of genes. We tested the method using data simulated under various error
      models and find that it performs well.

PMID- 12184812
TI  - Oxidative stress responses--what have genome-scale studies taught us?
AB  - Oxidative stress arises from an imbalance between generation and elimination of
      reactive oxygen species, often leading to cell death. Genomic tools are expanding
      our understanding of the antioxidant defenses aerobes have evolved and the
      recently discovered role(s) of reactive oxygen species in signaling.

PMID- 12184813
TI  - Principles of microbial alchemy: insights from the Streptomyces coelicolor genome
      sequence.
AB  - The world's most creative producers of natural pharmaceutical compounds are soil
      dwelling bacteria classified as Streptomyces. The availability of the recently
      completed Streptomyces coelicolor genome sequence provides a link between the
      folklore of antibiotics and other bioactive compounds to underlying biochemical,
      molecular genetic and evolutionary principles.

PMID- 12184815
TI  - The 14-3-3s.
AB  - Multiple members of the 14-3-3 protein family have been found in all eukaryotes
      so far investigated, yet they are apparently absent from prokaryotes. The major
      native forms of 14-3-3s are homo- and hetero-dimers, the biological functions of
      which are to interact physically with specific client proteins and thereby effect
      a change in the client. As a result, 14-3-3s are involved in a vast array of
      processes such as the response to stress, cell-cycle control, and apoptosis,
      serving as adapters, activators, and repressors. There are currently 133 full
      length sequences available in GenBank for this highly conserved protein family. A
      phylogenetic tree based on the conserved middle core region of the protein
      sequences shows that, in plants, the 14-3-3 family can be divided into two
      clearly defined groups. The core region encodes an amphipathic groove that binds
      the multitude of client proteins that have conserved 14-3-3-recognition
      sequences. The amino and carboxyl termini of 14-3-3 proteins are much more
      divergent than the core region and may interact with isoform-specific client
      proteins and/or confer specialized subcellular and tissue localization.

PMID- 12184814
TI  - MAP kinase phosphatases.
AB  - Mitogen-activated protein MAP kinases are key signal-transducing enzymes that are
      activated by a wide range of extracellular stimuli. They are responsible for the
      induction of a number of cellular responses, such as changes in gene expression,
      proliferation, differentiation, cell cycle arrest and apoptosis. Although
      regulation of MAP kinases by a phosphorylation cascade has long been recognized
      as significant, their inactivation through the action of specific phosphatases
      has been less studied. An emerging family of structurally distinct dual
      specificity serine, threonine and tyrosine phosphatases that act on MAP kinases
      consists of ten members in mammals, and members have been found in animals,
      plants and yeast. Three subgroups have been identified that differ in exon
      structure, sequence and substrate specificity.

PMID- 12184816
TI  - CLUSFAVOR 5.0: hierarchical cluster and principal-component analysis of
      microarray-based transcriptional profiles.
AB  - CLUSFAVOR (CLUSter and Factor Analysis with Varimax Orthogonal Rotation) 5.0
      standardizes input data; sorts data according to gene-specific coefficient of
      variation, standard deviation, average and total expression, and Shannon entropy;
      performs hierarchical cluster analysis using nearest-neighbor, unweighted pair
      group method using arithmetic averages (UPGMA), or furthest-neighbor joining
      methods, and Euclidean, correlation, or jack-knife distances; and performs
      principal-component analysis.

PMID- 12184817
TI  - Low agreement for assessing the risk of postoperative deep venous thrombosis when
      deciding prophylaxis strategies: a study using clinical vignettes.
AB  - BACKGROUND: Several clinical practice guidelines (CPG) on antithrombotic
      prophylaxis in surgical patients help to decide about the prophylaxis strategy
      based on the patient risk of deep venous thrombosis (DVT). However, the physician
      risk estimates of DVT could have little inter-observer reproducibility, which
      could lead to different individual prophylaxis practices. METHODS: Physicians
      were asked to evaluate DVT risk in eight clinical vignettes, describing actual
      patients cared for in our hospital. The vignettes included all possible levels of
      DVT risk. RESULTS: The degree of prophylaxis strategies accuracy was 63% (95% CI
      523-75%). Overall agreement was 0.32 (z = 7.61, p < 0.001) and for each level of
      risk kappa was 0.38 (z = 6.50, p < 0.001); 0.1 (z = 1.65, p < 0.049) and 0.5 (z =
      8.45, p < 0.001) for small, moderate and high risk group respectively
      CONCLUSIONS: Our results showed that there is poor agreement when physicians have
      to evaluate the risk for postoperative DVT, and in the cases of low and moderate
      risks of DVT there is the smallest agreement. In addition, the data also showed
      that the overall accuracy of DVT prophylaxis strategy was only moderate and the
      risk evaluation did not correlate to the selection of the strategy. The issue of
      inter-observers variability should be taken into account when CPG performance are
      analysed, especially when considering the risk-evaluation to choose the
      appropriate actions.

PMID- 12184820
TI  - Age- and density-dependent reproductive effort in male red deer.
AB  - Reproductive effort in female ungulates originates from gestation and lactation
      and has been studied extensively; however, no comparable studies of reproductive
      effort in males (due to fighting for access to mates) have, to our knowledge,
      previously been reported. Here, we report on weight loss of male red deer during
      the annual mating season--a direct measure of male reproductive effort (or
      somatic reproductive costs). The 'terminal investment' hypothesis predicts that
      reproductive effort should increase with age, given that costs remain stable. We
      also propose the 'mating strategy-effort' hypothesis, which predicts that
      reproductive effort peaks in prime-aged males, since they are most often the
      harem holders. Consistent with the mating strategy-effort hypothesis, relative
      weight loss during the rutting season peaked at prime age and was lower in
      younger and senescent males. Weight loss during the rut was relatively smaller as
      density increased and more so for older males. This is probably primarily due to
      males (particularly senescent males) starting their rut in poorer condition at
      high density. The pattern of reproductive effort in males with regard to age and
      density therefore differs markedly from the pattern reported for females.

PMID- 12184818
TI  - Adenovirus type 7 associated with severe and fatal acute lower respiratory
      infections in Argentine children.
AB  - BACKGROUND: Adenoviruses are the second most prevalent cause of acute lower
      respiratory infection of viral origin in children under four years of age in
      Buenos Aires, Argentina. The purpose of this study was to analyze the clinical
      features and outcome of acute lower respiratory infection associated with
      different adenovirus genotypes in children. METHODS: Twenty-four cases of acute
      lower respiratory infection and adenovirus diagnosis reported in a pediatric unit
      during a two-year period were retrospectively reviewed. Adenovirus was detected
      by antigen detection and isolation in HEp-2 cells. Adenovirus DNA from 17
      isolates was studied by restriction enzyme analysis with Bam HI and Sma I.
      RESULTS: Subgenus b was found in 82.3% of the cases, and subgenus c in 17.7%.
      Within subgenus b, only genotype 7 was detected, with genomic variant 7h in 85.7%
      (12/14) and genomic variant 7i in 14.3% (2/14). Mean age was 8.8 +/-; 6 months,
      and male to female ratio was 3.8: 1. At admission, pneumonia was observed in 71%
      of the cases and bronchiolitis in 29%. Malnutrition occurred in 37% of the cases;
      tachypnea in 79%; chest indrawing in 66%; wheezing in 58%; apneas in 16%; and
      conjunctivitis in 29%. Blood cultures for bacteria and antigen detection of other
      respiratory viruses were negative. During hospitalization, fatality rate was
      16.7% (4 /24). Of the patients who died, three had Ad 7h and one Ad 7i. Thus,
      fatality rate for adenovirus type 7 reached 28.6% (4/14). CONCLUSIONS: These
      results show the predominance of adenovirus 7 and high lethality associated with
      the genomic variants 7h and 7i in children hospitalized with acute lower
      respiratory infection.

PMID- 12184819
TI  - To what degree does cognitive impairment in Alzheimer's disease predict
      dependence of patients on caregivers?
AB  - BACKGROUND: Patients with Alzheimer's disease experience a progressive loss of
      cognitive function, and the ability to independently perform activities of daily
      life. Sometimes a dependent stage is reached quite early in the disease, when
      caregivers decide that the patients can no longer be left alone safely. This is
      an important aspect of Alzheimer's for patients, their families, and also health
      care providers. Understanding the relationship between a patient's current
      cognitive status and their need for care may assist clinicians when recommending
      an appropriate management plan. In this study, we investigated the relationship
      of cognitive function to dependence on caregivers before the patients reach a
      severe stage of the disease. METHODS: Data were obtained on 1,289 patients with
      mild-to-moderate Alzheimer's disease studied in two randomised clinical trials of
      galantamine (ReminylcircledR;). Cognition was assessed using the cognitive part
      of the Alzheimer's Disease Assessment Scale (ADAS-cog) and Mini-Mental State
      Examination (MMSE). Patients were considered dependent if they required >12 hours
      of supervision each day or had high care needs. The Disability Assessment for
      Dementia (DAD) scale was also used as a measure of dependence. Disability was
      predicted directly using MMSE and ADAS-cog and compared to predictions from
      converted scores. RESULTS: The odds ratio of dependence was significantly higher
      amongst the patients with worse cognitive impairment, adjusting for age, gender
      and antipsychotic medication use. For example, a 4-point difference in ADAS-cog
      score was associated with an increase of 17% (95% CI 11-23) in the adjusted odds
      for >12 hours of supervision, and of 35% (95% CI 28-43) for dependence.
      Disability predicted directly using actual ADAS-cog and scores converted from
      MMSE values had close agreement using the models developed. CONCLUSION: In
      patients with mild-to-moderate Alzheimer's disease, even relatively small degrees
      of poorer cognitive function increased the risk of losing the ability to live
      independently.

PMID- 12184821
TI  - How an orchid harms its pollinator.
AB  - Certain orchids produce flowers that mimic the sex pheromones and appearance of
      female insects in order to attract males by sexual deception for the purpose of
      pollination. In a series of field experiments, we found that the sexually
      deceptive orchid, Chiloglottis trapeziformis, can have a negative impact on its
      wasp pollinator Neozeleboria cryptoides. Male and female wasps, however, were
      affected differently by the orchid's deceit because of their different roles in
      the mimicry system. Male wasps could not discriminate between the chemical cues
      of orchids and female wasps, a vital signal in long-range attraction. Males,
      however, learn to avoid areas containing orchids. This strategy has implications
      for females attempting to attract mates in areas occupied by orchids. Compared
      with circumstances when females were on their own, females in the presence of
      orchids elicited fewer male approaches and no copulation attempts. Females in a
      large orchid patch also elicited fewer male approaches than females in a small
      patch. The nature of the orchid's impact on its wasp pollinator indicates an arms
      race evolutionary scenario in this interaction between plant and pollinator.

PMID- 12184822
TI  - Estimating the prevalence of inbreeding from incomplete pedigrees.
AB  - A previous review of inbreeding in natural populations suggested that close
      inbreeding (inbreeding coefficient f = 0.25) is generally rare in wild birds and
      mammals. However, the review did not assess rates of moderate inbreeding (f =
      0.125), which may make a rather larger contribution to overall inbreeding in a
      population. Furthermore, previous studies may have underestimated the prevalence
      of inbreeding in wild populations with incomplete pedigrees. By categorizing
      inbreeding events by the relationship of the parental pair, we suggest a simple
      method for estimating rates of close and moderate inbreeding from incomplete
      pedigree data. We applied this method to three wild populations of ruminants: red
      deer on Rum, Scotland, Soay sheep on Hirta, Scotland and reintroduced Arabian
      oryx on the Jiddat-al-Harasis, Oman. Although paternal half-sib pairs were the
      most common category of inbreeding in all three populations, there was
      considerable variation among populations in the frequencies of the various
      categories of inbreeding. This variation may be largely explained by differences
      in population size and dynamics, in maternal and paternal sibship size and in the
      overlap of reproductive lifespan of consecutive generations. Close and moderate
      inbreeding appear to be a routine part of breeding behaviour in these ruminant
      populations.

PMID- 12184823
TI  - Identifying the transition between single and multiple mating of queens in fungus
      growing ants.
AB  - Obligate mating of females (queens) with multiple males has evolved only rarely
      in social Hymenoptera (ants, social bees, social wasps) and for reasons that are
      fundamentally different from those underlying multiple mating in other animals.
      The monophyletic tribe of ('attine') fungus-growing ants is known to include
      evolutionarily derived genera with obligate multiple mating (the Acromyrmex and
      Atta leafcutter ants) as well as phylogenetically basal genera with exclusively
      single mating (e.g. Apterostigma, Cyphomyrmex, Myrmicocrypta). All attine genera
      share the unique characteristic of obligate dependence on symbiotic fungus
      gardens for food, but the sophistication of this symbiosis differs considerably
      across genera. The lower attine genera generally have small, short-lived colonies
      and relatively non-specialized fungal symbionts (capable of living independently
      of their ant hosts), whereas the four evolutionarily derived higher attine genera
      have highly specialized, long-term clonal symbionts. In this paper, we
      investigate whether the transition from single to multiple mating occurred
      relatively recently in the evolution of the attine ants, in conjunction with the
      novel herbivorous 'leafcutter' niche acquired by the common ancestor of
      Acromyrmex and Atta, or earlier, at the transition to rearing specialized long
      term clonal fungi in the common ancestor of the larger group of higher attines
      that also includes the genera Trachymyrmex and Sericomyrmex. We use DNA
      microsatellite analysis to provide unambiguous evidence for a single, late and
      abrupt evolutionary transition from exclusively single to obligatory multiple
      mating. This transition is historically correlated with other evolutionary
      innovations, including the extensive use of fresh vegetation as substrate for the
      fungus garden, a massive increase in mature colony size and morphological
      differentiation of the worker caste.

PMID- 12184824
TI  - Adjustments of ejaculation rates in response to risk of sperm competition in a
      fish, the bitterling (Rhodeus sericeus).
AB  - Game theory models of sperm competition predict that within species, males should
      increase their sperm expenditure when they have one competitor, but decrease
      expenditure with increasing numbers of competitors. So far, there have been few
      tests or support for this prediction. Here, we show that males of a freshwater
      fish, the European bitterling, Rhodeus sericeus, do indeed adjust their
      ejaculation rate to the number of male competitors by first increasing and then
      decreasing their ejaculation rates as the number of competitors increases.
      However, this occurred only under restricted conditions. Specifically, the
      prediction was upheld as long as no female had deposited eggs in the live mussels
      that are used as spawning sites. After one or more females had spawned, males did
      not decrease their ejaculation rates with the number of competitors, but instead
      they became more aggressive. This indicates that decreased ejaculation rate and
      increased aggression are alternative responses to increased risk of sperm
      competition.

PMID- 12184825
TI  - Going nuclear: gene family evolution and vertebrate phylogeny reconciled.
AB  - Gene duplications have been common throughout vertebrate evolution, introducing
      paralogy and so complicating phylogenetic inference from nuclear genes.
      Reconciled trees are one method capable of dealing with paralogy, using the
      relationship between a gene phylogeny and the phylogeny of the organisms
      containing those genes to identify gene duplication events. This allows us to
      infer phylogenies from gene families containing both orthologous and paralogous
      copies. Vertebrate phylogeny is well understood from morphological and
      palaeontological data, but studies using mitochondrial sequence data have failed
      to reproduce this classical view. Reconciled tree analysis of a database of 118
      vertebrate gene families supports a largely classical vertebrate phylogeny.

PMID- 12184826
TI  - A molecular phylogeny of ichthyophiid caecilians (Amphibia: Gymnophiona:
      Ichthyophiidae): out of India or out of South East Asia?
AB  - Recent molecular phylogenetic studies indicate that the rafting Indian plate
      harboured several isolated vertebrate lineages between ca. 130 and 56 Myr ago
      that dispersed and diversified 'out of India' following accretion with Eurasia. A
      single family of the amphibian order Gymnophiona, the Ichthyophiidae, presently
      occurs on the Indian plate and across much of South East Asia. Ichthyophiid
      phylogeny is investigated in order to test competing out of India and out of
      South East Asia hypotheses for their distribution. Partial sequences of
      mitochondrial 12S and 16S rRNA and cytochrome b genes for 20 ichthyophiids and
      proximate outgroups were assembled. Parsimony, maximum-likelihood and distance
      analyses all recover optimum trees in which uraeotyphlids plus Ichthyophis cf.
      malabarensis are the sister taxa to all other Ichthyophis, among which the South
      East Asian taxa are monophyletic. Tree topology and branch lengths indicate that
      the Indian lineages are more basal and older, and thus are more consistent with
      the hypothesis that ichthyophiids dispersed from the Indian subcontinent into
      South East Asia. The estimated relationships also support monophyly of Sri Lankan
      Ichthyophis, and non-monophyly of striped and unstriped Ichthyophis species
      groups. Mitochondrial DNA sequences provide evidence that should assist current
      problematic areas of caecilian taxonomy.

PMID- 12184827
TI  - The timing of sequences of saccades in visual search.
AB  - According to the LATER model (linear approach to thresholds with ergodic rate),
      the latency of a single saccade in response to target appearance can be
      understood as a decision process, which is subject to (i) variations in the rate
      of (visual) information processing; and (ii) the threshold for the decision. We
      tested whether the LATER model can also be applied to the sequences of saccades
      in a multiple fixation search, during which latencies of second and subsequent
      saccades are typically shorter than that of the initial saccade. We found that
      the distributions of the reciprocal latencies for later saccades, unlike those of
      the first saccade, are highly asymmetrical, much like a gamma distribution. This
      suggests that the normal distribution of the rate r, which the LATER model
      assumes, is not appropriate to describe the rate distributions of subsequent
      saccades in a scanning sequence. By contrast, the gamma distribution is also
      appropriate to describe the distribution of reciprocal latencies for the first
      saccade. The change of the gamma distribution parameters as a function of the
      ordinal number of the saccade suggests a lowering of the threshold for second and
      later saccades, as well as a reduction in the number of target elements analysed.

PMID- 12184828
TI  - Severe inbreeding depression in collared flycatchers (Ficedula albicollis).
AB  - The causes and magnitude of inbreeding depression are of considerable importance
      for a wide range of issues in evolutionary and conservation biology, but we have
      only a limited understanding of inbreeding depression in natural populations.
      Here, we present a study of inbreeding in a large wild population of collared
      flycatchers (Ficedula albicollis). Inbreeding was rare, to the extent that we
      detected only 1.04% of 2139 matings over 18 years that resulted in offspring with
      a non-zero inbreeding coefficient, f > 0. When it did occur, inbreeding caused a
      significant reduction in the egg-hatching rate, in fledgling skeletal size and in
      post-fledging juvenile survival, with the number of offspring being recruited to
      the breeding population from a nest of f = 0.25 being reduced by 94% relative to
      a non-inbred nest. A maximum-likelihood estimate of the number of lethal
      equivalents per gamete was very high at B = 7.47, indicating a substantial
      genetic load in this population. There was also a non-significant tendency for
      inbreeding depression to increase with the strength of selection on a trait. The
      probability of mating between close relatives (f = 0.25) increased throughout the
      breeding season, possibly reflecting increased costs of inbreeding avoidance. Our
      results illustrate how severe inbreeding depression and considerable genetic load
      may exist in natural populations, but detecting them may require extensive long
      term datasets.

PMID- 12184829
TI  - Rapid recovery of genetic diversity of stomatopod populations on Krakatau:
      temporal and spatial scales of marine larval dispersal.
AB  - Although the recovery of terrestrial communities shattered by the massive
      eruption of Krakatau in 1883 has been well chronicled, the fate of marine
      populations has been largely ignored. We examined patterns of genetic diversity
      in populations of two coral reef-dwelling mantis shrimp, Haptosquilla pulchella
      and Haptosquilla glyptocercus (Stomatopoda: Protosquillidae), on the islands of
      Anak Krakatau and Rakata. Genetic surveys of mitochondrial cytochrome oxidase c
      (subunit 1) in these populations revealed remarkably high levels of haplotypic
      and nucleotide diversity that were comparable with undisturbed populations
      throughout the Indo-Pacific. Recolonization and rapid recovery of genetic
      diversity in the Krakatau populations indicates that larval dispersal from
      multiple and diverse source populations contributes substantially to the
      demographics of local populations over intermediate temporal (tens to hundreds of
      years) and spatial scales (tens to hundreds of kilometres). Natural experiments
      such as Krakatau provide an excellent mechanism to investigate marine larval
      dispersal and connectivity. Results from stomatopods indicate that marine
      reserves should be spaced no more than 50-100 km apart to facilitate ecological
      connectivity via larval dispersal.

PMID- 12184830
TI  - Host-pathogen interactions in a varying environment: temperature, behavioural
      fever and fitness.
AB  - We demonstrate how variable temperatures, mediated by host thermoregulation and
      behavioural fever, critically affect the interaction between a host (the desert
      locust, Schistocerca gregaria) and a pathogen (the fungus Metarhizium anisopliae
      var. acridum). By means of behavioural thermoregulation, infected locusts can
      raise their body temperatures to fever levels. The adaptive value of this
      behaviour was examined using three thermal regimes wherein maximum body
      temperatures achievable were: (i) below, or (ii) at normally preferred
      temperatures, or were (iii) unrestricted, allowing heightened fever temperatures.
      All infected locusts ultimately succumbed to disease, with median survival times
      of 8, 15 and 21 days post-infection, respectively. Crucially, only those locusts
      able to fever produced viable offspring. This represents, to our knowledge, the
      first demonstration of the adaptive value of behavioural fever following
      infection with a naturally occurring pathogen. By contrast, although normal host
      thermoregulation moderately reduced pathogen reproduction (by 35%), there was no
      additional negative effect of fever, resulting in an asymmetry in the fitness
      consequences of fever for the host and the pathogen. The dependency of the host
      pathogen interaction upon external abiotic conditions has implications for how
      virulence and resistance are treated both theoretically and in the management of
      pests and diseases.

PMID- 12184831
TI  - Analysing noisy time-series: describing regional variation in the cyclic dynamics
      of red grouse.
AB  - We develop a method for describing the periodicity of noisy 'quasi-cyclic' time
      series based on integrals of their power spectra corresponding to different
      frequency intervals that we use to classify time-series as 'strongly cyclic',
      'weakly cyclic' or 'non-cyclic'. We apply this analysis to over 300 time-series
      of shooting records of red grouse from 289 moors located in 20 regions of the UK.
      Time-series from 63 of these populations were not distinguishable from white
      noise, but significant evidence of cyclic behaviour in the 2-15 year range was
      detected in time-series from 183 other populations. Time-series from the
      remaining 43 populations, though distinguishable from white noise, did not
      exhibit consistently recognizable cyclic behaviour in the same period range.
      Cyclic populations exhibit an average periodicity of 8.3 years, but only 20% of
      these populations cycle with a period of four to six years. Geographically,
      grouse populations are remarkable more for their dynamic heterogeneity than for
      any observable regularity. The relationship between the location of populations
      and their dynamical behaviour is weak. The prevalence of cyclic time-series
      within a region did not significantly differ from the overall average value. Moor
      region explained 22% of the variation in periodicity, differing from the overall
      mean in three regions. Average periodicity increases significantly from 6.8 to
      8.9 years from the most southerly to most northerly populations. However,
      latitude explains only 5.3% of the variation in periodicity of the cycles.

PMID- 12184832
TI  - Positive fitness consequences of interspecific interaction with a potential
      competitor.
AB  - The coexistence of species sharing mutual resources is usually thought to be
      limited by negative processes such as interspecific competition. This is because
      an overlap in resource use leads to negative fitness consequences, and traits
      favouring avoidance of potential competitors, for example in habitat selection,
      are therefore selected for. However, species interactions are acknowledged to
      vary from negative (competition) to mutualism, although empirical evidence for
      positive interspecific interactions from natural communities of other than plants
      and sessile animals is scarce. Here, we experimentally examined the habitat
      selection and its fitness consequences of a migrant bird, the pied flycatcher
      (Ficedula hypoleuca), in relation to the presence of competitively superior
      birds, resident titmice (Parus spp.). Experiments were conducted on two spatial
      scales: landscape and nest-site scale. We demonstrate that pied flycatchers were
      attracted to and accrued fitness benefits from the presence of titmice.
      Flycatchers breeding in tight association with titmice initiated breeding
      earlier, had larger broods and heavier young than solitarily breeding
      flycatchers. This paradoxical result indicates that species interactions may
      switch from negative to positive and that the coexistence of species is not
      always restricted by negative costs caused by other species.

PMID- 12184833
TI  - The role of parasites in the dynamics of a reindeer population.
AB  - Even though theoretical models show that parasites may regulate host population
      densities, few empirical studies have given support to this hypothesis. We
      present experimental and observational evidence for a host-parasite interaction
      where the parasite has sufficient impact on host population dynamics for
      regulation to occur. During a six year study of the Svalbard reindeer and its
      parasitic gastrointestinal nematode Ostertagia gruehneri we found that
      anthelminthic treatment in April-May increased the probability of a reindeer
      having a calf in the next year, compared with untreated controls. However,
      treatment did not influence the over-winter survival of the reindeer. The annual
      variation in the degree to which parasites depressed fecundity was positively
      related to the abundance of O. gruehneri infection the previous October, which in
      turn was related to host density two years earlier. In addition to the treatment
      effect, there was a strong negative effect of winter precipitation on the
      probability of female reindeer having a calf. A simple matrix model was
      parameterized using estimates from our experimental and observational data. This
      model shows that the parasite-mediated effect on fecundity was sufficient to
      regulate reindeer densities around observed host densities.

PMID- 12184834
TI  - Duration of heart disease visits by elderly patients: productivity versus
      quality.
AB  - A balance should be reached between physician productivity and clinical quality,
      since the first comes at the expense of the second. The study described here used
      the National Ambulatory Medical Care Survey (NAMCS) to demonstrate that visit
      length for elderly heart disease patients is related to both appropriate (i.e.
      clinical) patient differences and to less justifiable factors. Both demand
      management and managerial control strategies should be considered.

PMID- 12184835
TI  - Reconceptualizing case management in theory and practice: a frontline
      perspective.
AB  - 'Case management' in the health and social service sector is controversial,
      highly political and saturated with conflicting agendas among stakeholders.
      Research was conducted recently to explore the role of case managers in three
      evolving, Australian-based, long-term care, case management models. The findings
      have relevance to countries worldwide that contend with delivering quality care
      that is cost effective. The research captures the perspectives of 51 open-ended
      interviews with front-line case managers who have first-hand knowledge of the
      models' effect on their clients and on their own roles. Contrary to the rhetoric
      that case management is client-centred, case management is concluded to be
      'system centred' based on a unilateral approach taken by each of the three
      models. Case managers had a limited ability to attain necessary services for
      clients. Success was dependent on the range of case managers' skills and
      experience, relationship with the client, degree of job satisfaction, level of
      influence in the health and social system and ability to collaborate with
      relevant professionals. The relationship between the three primary influences
      (system, model, client) affecting case managers' pursuit of achieving appropriate
      client services was also reviewed. A reconceptualized multidimensional approach,
      or 'neo-process-centred' case management, is proposed. The revised approach can
      be applied to existing and new models and has direct implications for policy
      makers, management and practitioners aspiring to improve client care within
      existing constraints.

PMID- 12184836
TI  - Meeting patient expectations: healthcare professionals and service re
      engineering.
AB  - A central theme underpinning the reform of healthcare systems in western
      economies since the 1980s has been the emphasis on reorienting service provision
      around the patient. Healthcare organizations have been forced to re-appraise the
      design of the service delivery process, specifically the service encounter, to
      take account of these changing patient expectations. This reorientation of
      healthcare services around the patient has fundamental implications for
      healthcare professionals, specifically challenging the dominance of service
      professionals in the design and delivery of health services. Utilizing a
      qualitative methodological framework, this paper explores the responses of
      healthcare professionals to service redesign initiatives implemented in acute NHS
      hospitals in Scotland and considers the implications of such professional
      responses for the development of patient-focused service delivery. Within this,
      it specifically examines evolving professional perspectives on the place of a
      service user focus in a publicly funded healthcare system, professional attitudes
      towards private sector managerial practices, and the dynamics of changing
      professional behaviour.

PMID- 12184838
TI  - Estimation of the total number of hospital admissions and bed requirements for
      2011: the case for Greece.
AB  - In order to improve the existing situation in the Greek health sector, there is a
      pronounced need for flexible planning methods, together with the development of
      long-term perspectives on policy formulation. The team started with the
      collection of relevant data, since the first priority was to have a detailed
      knowledge of the current situation and conditions upon which projections of
      likely future developments can be based. The aim of this paper is to identify a
      reliable method for the estimation of future admissions to hospitals, by age
      groups and sex. These estimates have been used as the basis for projecting
      hospital bed requirements by the final year of the planning period (2011).
      Accurate knowledge and analysis of hospital bed requirements in the future would
      be a fundamental aid to health care planning given that the increase in the
      proportion of elderly people will lead to differences in the demand for health
      services. To reduce uncertainty, a main parameter has been introduced and used in
      all projections, with very limited total variation. Although all relevant studies
      resulted in a rigid, one estimation (projection) point, we have estimated upper
      and lower limits of projections, to make the corresponding plan more flexible.

PMID- 12184837
TI  - A review of the literature: interventions to maximize capacity to consent and
      reduce anxiety of women with learning disabilities preparing for a cervical smear
      test.
AB  - Due to the complex nature of the cervical screening for women with learning
      disabilities, this literature review has several different strands. The aim of
      which is to give a general overview of the literature available about women with
      learning disabilities and cervical screening. Discussing key issues in relation
      to uptake, access and risk factors associated with cervical screening. The role
      of the learning disability nurse in supporting access to cervical screening
      services within primary care will be explored. The notion that anxiety and a
      woman's capacity to consent impacts on her accessing cervical screening services
      and ultimately undergoing a cervical smear test, will be examined. Relaxation
      techniques with regard to ascertaining which techniques are more effective when
      used with individuals with a learning disability will also be discussed.

PMID- 12184839
TI  - Managing care and cure -- up and down, in and out.
AB  - Managing may be managing, but it is practiced in a wide range of ways in the so
      called 'healthcare' system. All or in some cases part of a day in the life of
      seven managers is described and then analysed, separately and then together. This
      presents a consistent picture of the varieties as well as the discontinuities in
      managing this hopefully integrated system.

PMID- 12184840
TI  - Scalable hybrid computation with spikes.
AB  - We outline a hybrid analog-digital scheme for computing with three important
      features that enable it to scale to systems of large complexity: First, like
      digital computation, which uses several one-bit precise logical units to
      collectively compute a precise answer to a computation, the hybrid scheme uses
      several moderate-precision analog units to collectively compute a precise answer
      to a computation. Second, frequent discrete signal restoration of the analog
      information prevents analog noise and offset from degrading the computation. And,
      third, a state machine enables complex computations to be created using a
      sequence of elementary computations. A natural choice for implementing this
      hybrid scheme is one based on spikes because spike-count codes are digital, while
      spike-time codes are analog. We illustrate how spikes afford easy ways to
      implement all three components of scalable hybrid computation. First, as an
      important example of distributed analog computation, we show how spikes can
      create a distributed modular representation of an analog number by implementing
      digital carry interactions between spiking analog neurons. Second, we show how
      signal restoration may be performed by recursive spike-count quantization of
      spike-time codes. And, third, we use spikes from an analog dynamical system to
      trigger state transitions in a digital dynamical system, which reconfigures the
      analog dynamical system using a binary control vector; such feedback interactions
      between analog and digital dynamical systems create a hybrid state machine (HSM).
      The HSM extends and expands the concept of a digital finite-state-machine to the
      hybrid domain. We present experimental data from a two-neuron HSM on a chip that
      implements error-correcting analog-to-digital conversion with the concurrent use
      of spike-time and spike-count codes. We also present experimental data from
      silicon circuits that implement HSM-based pattern recognition using spike-time
      synchrony. We outline how HSMs may be used to perform learning, vector
      quantization, spike pattern recognition and generation, and how they may be
      reconfigured.

PMID- 12184841
TI  - Learning nonregular languages: a comparison of simple recurrent networks and
      LSTM.
AB  - In response to Rodriguez's recent article (2001), we compare the performance of
      simple recurrent nets and long short-term memory recurrent nets on context-free
      and context-sensitive languages.

PMID- 12184842
TI  - Center-crossing recurrent neural networks for the evolution of rhythmic behavior.
AB  - A center-crossing recurrent neural network is one in which the null
      (hyper)surfaces of each neuron intersect at their exact centers of symmetry,
      ensuring that each neuron's activation function is centered over the range of net
      inputs that it receives. We demonstrate that relative to a random initial
      population, seeding the initial population of an evolutionary search with center
      crossing networks significantly improves both the frequency and the speed with
      which high-fitness oscillatory circuits evolve on a simple walking task. The
      improvement is especially striking at low mutation variances. Our results suggest
      that seeding with center-crossing networks may often be beneficial, since a wider
      range of dynamics is more likely to be easily accessible from a population of
      center-crossing networks than from a population of random networks.

PMID- 12184843
TI  - Reply to Carreira-Perpinan and Goodhill. Are visual cortex maps optimized for
      coverage?

PMID- 12184844
TI  - Dynamics of the firing probability of noisy integrate-and-fire neurons.
AB  - Cortical neurons in vivo undergo a continuous bombardment due to synaptic
      activity, which acts as a major source of noise. Here, we investigate the effects
      of the noise filtering by synapses with various levels of realism on integrate
      and-fire neuron dynamics. The noise input is modeled by white (for instantaneous
      synapses) or colored (for synapses with a finite relaxation time) noise.
      Analytical results for the modulation of firing probability in response to an
      oscillatory input current are obtained by expanding a Fokker-Planck equation for
      small parameters of the problem - when both the amplitude of the modulation is
      small compared to the background firing rate and the synaptic time constant is
      small compared to the membrane time constant. We report here the detailed
      calculations showing that if a synaptic decay time constant is included in the
      synaptic current model, the firing-rate modulation of the neuron due to an
      oscillatory input remains finite in the high-frequency limit with no phase lag.
      In addition, we characterize the low-frequency behavior and the behavior of the
      high-frequency limit for intermediate decay times. We also characterize the
      effects of introducing a rise time to the synaptic currents and the presence of
      several synaptic receptors with different kinetics. In both cases, we determine,
      using numerical simulations, an effective decay time constant that describes the
      neuronal response completely.

PMID- 12184846
TI  - Preintegration lateral inhibition enhances unsupervised learning.
AB  - A large and influential class of neural network architectures uses
      postintegration lateral inhibition as a mechanism for competition. We argue that
      these algorithms are computationally deficient in that they fail to generate, or
      learn, appropriate perceptual representations under certain circumstances. An
      alternative neural network architecture is presented here in which nodes compete
      for the right to receive inputs rather than for the right to generate outputs.
      This form of competition, implemented through preintegration lateral inhibition,
      does provide appropriate coding properties and can be used to learn such
      representations efficiently. Furthermore, this architecture is consistent with
      both neuroanatomical and neurophysiological data. We thus argue that
      preintegration lateral inhibition has computational advantages over conventional
      neural network architectures while remaining equally biologically plausible.

PMID- 12184845
TI  - Integrate-and-fire neurons driven by correlated stochastic input.
AB  - Neurons are sensitive to correlations among synaptic inputs. However, analytical
      models that explicitly include correlations are hard to solve analytically, so
      their influence on a neuron's response has been difficult to ascertain. To gain
      some intuition on this problem, we studied the firing times of two simple
      integrate-and-fire model neurons driven by a correlated binary variable that
      represents the total input current. Analytic expressions were obtained for the
      average firing rate and coefficient of variation (a measure of spike-train
      variability) as functions of the mean, variance, and correlation time of the
      stochastic input. The results of computer simulations were in excellent agreement
      with these expressions. In these models, an increase in correlation time in
      general produces an increase in both the average firing rate and the variability
      of the output spike trains. However, the magnitude of the changes depends
      differentially on the relative values of the input mean and variance: the
      increase in firing rate is higher when the variance is large relative to the
      mean, whereas the increase in variability is higher when the variance is
      relatively small. In addition, the firing rate always tends to a finite limit
      value as the correlation time increases toward infinity, whereas the coefficient
      of variation typically diverges. These results suggest that temporal correlations
      may play a major role in determining the variability as well as the intensity of
      neuronal spike trains.

PMID- 12184847
TI  - On optimality in auditory information processing.
AB  - We study limits for the detection and estimation of weak sinusoidal signals in
      the primary part of the mammalian auditory system using a stochastic Fitzhugh
      Nagumo model and an action-recovery model for synaptic depression. Our overall
      model covers the chain from a hair cell to a point just after the synaptic
      connection with a cell in the cochlear nucleus. The information processing
      performance of the system is evaluated using so-called phi-divergences from
      statistics that quantify "dissimilarity" between probability measures and are
      intimately related to a number of fundamental limits in statistics and
      information theory (IT). We show that there exists a set of parameters that can
      optimize several important phi-divergences simultaneously and that this set
      corresponds to a constant quiescent firing rate (QFR) of the spiral ganglion
      neuron. The optimal value of the QFR is frequency dependent but is essentially
      independent of the amplitude of the signal (for small amplitudes). Consequently,
      optimal processing according to several standard IT criteria can be accomplished
      for this model if and only if the parameters are "tuned" to values that
      correspond to one and the same QFR. This offers a new explanation for the QFR and
      can provide new insight into the role played by several other parameters of the
      peripheral auditory system.

PMID- 12184848
TI  - Computational capacity of an odorant discriminator: the linear separability of
      curves.
AB  - We introduce and study an artificial neural network inspired by the probabilistic
      receptor affinity distribution model of olfaction. Our system consists of N
      sensory neurons whose outputs converge on a single processing linear threshold
      element. The system's aim is to model discrimination of a single target odorant
      from a large number p of background odorants within a range of odorant
      concentrations. We show that this is possible provided p does not exceed a
      critical value p(c) and calculate the critical capacity alpha(c) = p(c)/N. The
      critical capacity depends on the range of concentrations in which the
      discrimination is to be accomplished. If the olfactory bulb may be thought of as
      a collection of such processing elements, each responsible for the discrimination
      of a single odorant, our study provides a quantitative analysis of the potential
      computational properties of the olfactory bulb. The mathematical formulation of
      the problem we consider is one of determining the capacity for linear
      separability of continuous curves, embedded in a large-dimensional space. This is
      accomplished here by a numerical study, using a method that signals whether the
      discrimination task is realizable, together with a finite-size scaling analysis.

PMID- 12184849
TI  - Mixture of experts classification using a hierarchical mixture model.
AB  - A three-level hierarchical mixture model for classification is presented that
      models the following data generation process: (1) the data are generated by a
      finite number of sources (clusters), and (2) the generation mechanism of each
      source assumes the existence of individual internal class-labeled sources
      (subclusters of the external cluster). The model estimates the posterior
      probability of class membership similar to a mixture of experts classifier. In
      order to learn the parameters of the model, we have developed a general training
      approach based on maximum likelihood that results in two efficient training
      algorithms. Compared to other classification mixture models, the proposed
      hierarchical model exhibits several advantages and provides improved
      classification performance as indicated by the experimental results.

PMID- 12184850
TI  - On the emergence of rules in neural networks.
AB  - A simple associationist neural network learns to factor abstract rules (i.e.,
      grammars) from sequences of arbitrary input symbols by inventing abstract
      representations that accommodate unseen symbol sets as well as unseen but similar
      grammars. The neural network is shown to have the ability to transfer grammatical
      knowledge to both new symbol vocabularies and new grammars. Analysis of the state
      space shows that the network learns generalized abstract structures of the input
      and is not simply memorizing the input strings. These representations are context
      sensitive, hierarchical, and based on the state variable of the finite-state
      machines that the neural network has learned. Generalization to new symbol sets
      or grammars arises from the spatial nature of the internal representations used
      by the network, allowing new symbol sets to be encoded close to symbol sets that
      have already been learned in the hidden unit space of the network. The results
      are counter to the arguments that learning algorithms based on weight adaptation
      after each exemplar presentation (such as the long term potentiation found in the
      mammalian nervous system) cannot in principle extract symbolic knowledge from
      positive examples as prescribed by prevailing human linguistic theory and
      evolutionary psychology.

PMID- 12184851
TI  - Alterations in BDNF and synapsin I within the occipital cortex and hippocampus
      after mild traumatic brain injury in the developing rat: reflections of injury
      induced neuroplasticity.
AB  - Brain-derived neurotrophic factor (BDNF), its signal transduction receptor trkB,
      and its downstream effector, synapsin I, were measured in the hippocampus and
      occipital cortex of young animals after fluid-percussion brain injury (FPI).
      Isofluorane anaesthetized postnatal day 19 rats were subjected to a mild lateral
      FPI or sham injury. Rats were sacrificed at 24 h, 7 days, or 14 days after injury
      in order to determine mRNA expression. Additional animals were sacrificed at 7
      and 14 days after injury for protein analysis. Only FPI animals exhibited
      hemispheric differences in BDNF levels. These animals exhibited a contralateral
      increase, ranging from 40% to 75%, in BDNF mRNA within both the hippocampus and
      occipital cortex at 24 h and 7 days after injury. The increase in message within
      the occipital cortex was accompanied by an increase in BDNF protein at 7 and 14
      days after injury. However, hippocampal BDNF protein increased in both
      hemispheres at postinjury day 7 and was restricted to the ipsilateral hippocampus
      at postinjury day 14. At postinjury day 7, both trkB and synapsin I mRNA
      expression increased ipsilaterally and decreased contralaterally in the occipital
      cortex. In addition, synapsin I phosphorylation was increased by 20% in the
      ipsilateral cortex and by 30% in the hippocampus on this day. These results
      indicate that the developing brain responds to a mild injury by modifying factors
      related to synaptic plasticity and suggest that regions remote from the site of
      injury express neurotrophic signals potentially needed for compensatory
      responses.

PMID- 12184852
TI  - Rapid subcellular redistribution of Bax precedes caspase-3 and endonuclease
      activation during excitotoxic neuronal apoptosis in rat brain.
AB  - Neuronal apoptosis is induced prominently in the newborn rodent brain by
      glutamate receptor excitotoxicity and related insults, including trauma and
      hypoxia-ischemia. However, the molecular mechanisms of this neurodegeneration are
      unclear. We tested the hypothesis that changes in the subcellular distribution of
      the proapoptotic protein Bax precede the activation of downstream apoptosis
      effector mechanisms such as caspase-3 cleavage and endonuclease activation during
      the progression of excitotoxic neuronal apoptosis in the striatum of newborn rat.
      Kainic acid (4 nmol) was injected into striatum of anesthetized 7-day-old rats,
      and the animals were killed at 2, 6, 12, and 24 h postinsult. Controls were age
      matched, vehicle-injected, or naive rats. Counts of ultrastructurally confirmed
      striatal neuron apoptosis in brain sections were highest at 24 h. Striatal tissue
      was microdissected and fractionated into cytosolic, mitochondrial-, and nuclear
      enriched compartments. Immunoblots showed that Bax translocates from the cytosol
      fraction to the mitochondrial fraction, with maximal translocation by 2 h in the
      absence of changes in mitochondrial accumulation. Cleaved caspase-3 levels
      increase progressively in both cytosolic and mitochondrial fractions between 6
      and 24 h. Cleaved caspase-3 accumulates in apoptotic striatal neurons as shown by
      immunolocalization. Internucleosomal fragmentation of DNA coincides with caspase
      3 cleavage. We conclude that rapid translocation of Bax to mitochondria precedes
      caspase-3 and endonuclease activation during excitotoxic neuronal apoptosis in
      newborn rat brain and that initiation of this death cascade occurs within 2 h
      after glutamate receptor activation.

PMID- 12184853
TI  - Cyclosporin A improves brain tissue oxygen consumption and learning/memory
      performance after lateral fluid percussion injury in rats.
AB  - Traumatic brain injury (TBI) triggers a complex pathophysiological cascade,
      leading to cell death. A major factor in the pathogenesis of TBI is neuronal
      overloading with calcium, causing the opening of mitochondrial permeability
      transition pores (MPTP), which consequently inhibit normal mitochondrial
      function. The immunosuppressant Cyclosporin A (CsA) has been shown to block
      MPTPs, and to be neuroprotective in ischemia and TBI. However, the translation of
      these effects on mitochondrial function, into behavioral endpoints has not been
      investigated thoroughly. Therefore, we tested the effect of a low, clinically
      evaluated, CsA dose of 0.125 mg/kg (infused for 3 h) and a higher "known"
      neuroprotective dose of 18.75 mg/kg on brain tissue O(2) consumption, and on
      motor and cognitive performance following lateral fluid percussion injury (FPI)
      in rats. CsA at both concentrations abolished the 25% decrease in O(2)
      consumption (VO(2)), seen in saline-treated animals at 5 h post-FPI. Furthermore,
      the lower dose of CsA also ameliorated acute motor deficits (days 1-5 post-FPI)
      and learning and memory impairments in a Morris water maze test on days 11-15
      post-FPI. Although, the higher dose of CsA improved cognitive performance, it
      worsened acute motor functional recovery. These results suggest, that the CsA
      induced preservation of mitochondrial function, as assessed by tissue O(2)
      consumption, directly translated into improvements in motor and cognitive
      behavior.

PMID- 12184854
TI  - Traumatic axonal injury after closed head injury in the neonatal pig.
AB  - Closed head injury is the leading cause of morbidity and mortality in infants and
      children, and results in pathologies such as diffuse axonal injury (DAI) and
      subarachnoid hematoma (SAH). To better understand the mechanical environment
      associated with closed head injury in the pediatric population, animal models
      that include salient features of human infant brain must be utilized. Based on
      detailed information regarding the parallels between brain development in the pig
      and the human, the 3-5-day-old piglet was used to represent the infant at less
      than 3 months of age. Anesthetized piglets (n = 7) were subjected to rapid,
      inertial (nonimpact) rotation of the head about its axial plane and sacrificed at
      6 h postinjury. Immediately following injury, five of seven piglets were apneic,
      with an absence of pupillary and pain reflexes. All piglets exhibited severe coma
      immediately postinjury, but recovered by sacrifice time. Blood was present on the
      surface of the frontal lobes, cerebellum, and brainstem, and subarachnoid
      hemorrhage was evident in the frontal cortex. In six of seven brain-injured
      piglets, accumulation of the 68-kDa neurofilament protein was evident in
      contiguous axons (swollen) and occasionally in disconnected axons (axonal bulbs),
      suggestive of traumatic axonal injury (TAI). Mapping of the regional pattern of
      TAI revealed injured axons predominantly in central and peripheral white matter
      tracts in the frontal and temporal lobes and in the midbrain. The number of
      injured axons was equivalent in both hemispheres, and did not correlate to the
      load applied to the head. Together, these data demonstrate that rapid rotation of
      the piglet head without impact results in SAH and TAI, similar to that observed
      in children following severe brain trauma.

PMID- 12184855
TI  - Outcome of traumatic brain injuries in 1,508 patients: impact of prehospital
      care.
AB  - This article describes the outcome of 1,508 patients with traumatic brain
      injuries (TBI) treated in a single neurosurgical unit over an 8-year period. Our
      aim has been to compare those outcomes with our previous results and with other
      large patient series. Another important goal was to evaluate the effect of the
      introduction of a 4-year ongoing study initiated in January 1993 using a new
      strategy of prehospital care on postresuscitation Glasgow Coma Score (GCS) and
      Glasgow Outcome Score (GOS). Results from the 1,508 patients showed good recovery
      or moderate disability in 69%, severe disability or vegetative state in 11%, and
      a mortality rate of 20%. When outcome of the most severely injured patients (GCS
      < or = 8) was compared with those of our previous and other large international
      patient series, more favorable outcome figures were shown in the present study.
      To evaluate the impact of the improved prehospital care after half of the study
      period, a logistic regression analysis showed after January 1993 a significantly
      increased expected odds/ratio for a postresuscitation GCS 8-15 rather than a GCS
      3-4 (odds/ratio: 2.2; p < 0.001). For patients with postresuscitation GCS 5-7 and
      8-15, the expected odds/ratio for a GOS 4-5 instead of GOS 1 increased
      significantly (odds/ratio: 2.2 and 1.7, respectively; p < 0.05-0.01). For
      patients with GCS 3-4, an increased expected odds/ratio (2.0; p < 0.05) for a GOS
      2-3 rather than a GOS 1 was seen. The principal conclusion is that outcome for
      the severely injured patients in the present study is more favorable than in
      other large series of TBI. We posit that the introduction of effective
      prehospital care most likely contributed to the improved postresuscitation
      neurological status and consequently to the better outcome observed after January
      1993.

PMID- 12184856
TI  - Early indicators of prognosis in 846 cases of severe traumatic brain injury.
AB  - A number of factors, including Glasgow coma scale (GCS) score, age, pupillary
      response and size, hypoxia, hyperthermia, and high intracranial pressure, may
      play an important role in predicting the outcome of traumatic brain injury. Eight
      hundred forty-six cases of severe traumatic brain injury (GCS < or = 8) were
      analyzed retrospectively to clarify the effects of multiple factors on the
      prognosis of patients. At 1 year after injury, the outcomes in these cases were
      as follows: good recovery, 31.56%; moderate disability, 14.07%; severe disability
      24.35%; vegetative status, 0.59%; and death, 29.43%. The outcomes were strongly
      correlated (p < 0.05) with GCS score, age, pupillary response and size, hypoxia,
      hyperthermia, and high intracranial pressure (ICP). These findings indicate that
      prevention of hypoxia, control of high ICP, and prevention of hyperthermia may be
      useful means for improving the outcome of patients with severe head injury.

PMID- 12184857
TI  - Chronic intrathecal baclofen treatment and withdrawal: I. Changes in ankle torque
      and hind limb posture in normal rats.
AB  - This study evaluated reflex excitability and locomotor changes during chronic
      intrathecal infusion of the GABAb agonist baclofen (ITB) and its withdrawal, in
      the rat. We observed sustained velocity dependent decreases in ankle torque
      during four weeks of ITB treatment. These changes were correlated with a
      significant reduction of the EMG burst magnitude time locked to the dynamic phase
      of ankle dorsiflexion during the first ITB treatment week. However, a
      considerable recovery of EMG magnitude was observed during the third and fourth
      weeks of treatment. During baclofen withdrawal, significantly increased velocity
      dependent ankle torque was observed for 4 weeks. These increases in ankle torque
      were correlated with increased magnitudes of EMG time locked to the dynamic phase
      of ankle rotation. Measures of hind limb axis and base of support were obtained
      using analysis of footprints on a treadmill during ITB treatment and withdrawal
      periods. During ITB treatment and for up to 7 weeks of withdrawal, hindlimb axis
      and base of support were significantly altered compared with vehicle controls.
      These studies were performed to provide a foundation for evaluation of treatment
      and withdrawal in the setting of experimental chronic contusion spinal cord
      injury.

PMID- 12184858
TI  - Systemic administration of a calpain inhibitor reduces behavioral deficits and
      blood-brain barrier permeability changes after experimental subarachnoid
      hemorrhage in the rat.
AB  - Increases in intracellular calcium and subsequent activation of calcium-activated
      proteases (e.g., calpains) may play a critical role in central nervous system
      injury. Several studies have implicated calpain activation following subarachnoid
      hemorrhage (SAH). This study evaluated the effect of a calpain inhibitor
      administration following SAH in the rat on behavioral deficits (postinjury days 1
      5, employing a battery of well-characterized assessment tasks), and blood-brain
      barrier permeability changes (48 h post-SAH, quantifying the microvascular
      alterations according to the extravasation of protein-bound Evans Blue using a
      spectrophotofluorimetric technique). Rats were injected with 400 microl of
      autologous blood into the cisterna magna to induce SAH. Within 5 min after the
      surgical procedure, Calpain Inhibitor II or vehicle was continuously administered
      intravenously for 2 days. Results indicated that Calpain Inhibitor II treatment
      after SAH significantly improved (a) beam balance time (day 1, p < 0.05), but not
      beam balance score, (b) latency to traverse the beam on days 1-4 (day 1-3, p <
      0.001; day 4, p < 0.01), and (c) loss in body weight on days 4-5 (p < 0.05).
      Evans Blue dye extravasation was significantly less in SAH Calpain Inhibitor II
      treated rats compared to SAH vehicle-treated rats in seven out of the eight brain
      regions studied (p < 0.001, 0.01, and 0.05). These results suggest that
      pharmacological inhibition of a relatively selective, membrane-permeant calpain
      inhibitor can significantly reduce some pathophysiological SAH consequences, and
      indicate that the inhibition of calpain may be a beneficial therapeutic approach
      to reduce post-SAH global brain dysfunction.

PMID- 12184859
TI  - Changes in c-Fos protein expression in the rat cuneate nucleus after electric
      stimulation of the transected median nerve.
AB  - In this study we investigate temporal changes in Fos expression in cuneate
      neurons after a high-threshold electrical stimulation of the transected median
      nerve in rats. Two hours after injury of the median nerve when given electrical
      stimulation, c-Fos-immunoreactive (c-Fos-IR) cells were barely detected in the
      ipsilateral cuneate nucleus (CN). A few c-Fos-IR cells, however, were observed in
      the ipsilateral CN at 5 days. A marked increase in c-Fos-IR cells was observed at
      2, 3, and 4 weeks, but levels subsided thereafter. Labeled cells were totally
      diminished by 16 weeks. The statistical analysis showed that the mean density of
      c-Fos-IR cells throughout the CN at 4 weeks was significantly higher than at
      other post-surgical time points, except for 3 weeks. Furthermore, the mean
      density of c-Fos-IR cells in the middle region of the CN was markedly higher than
      in other areas of the nucleus. The mean density of c-Fos-IR cells in the middle
      region at 4 weeks (mean density = 35.9 +/- 3.0 cells/section) was considerably
      higher than at other time points. Combined retrograde Fluorogold (FG) labeling
      and c-Fos immunocytochemistry showed that throughout the CN about 60% (2270/3652)
      of the c-Fos-IR cells contained FG, confirming that they were cuneothalamic
      projection neurons (CTNs). Moreover, the percentage of double-labeled cells in
      the middle region at 2 weeks (78.9 +/- 0.6%) was significantly greater than at 3
      (70.2 +/- 3.4%) and 4 weeks (66.0b +/- 1.4%) after injury. Although the mechanism
      leading to the vigorous c-Fos expression in the CTNs following the electrical
      stimulation of the transected median nerve remains unclear the hyperexcitable
      CTNs may transmit the neuropathic nociceptive sensation to the thalamus after the
      median nerve injury.

PMID- 12184860
TI  - Aerosols in bronchiolitis.
AB  - Bronchiolitis is a common illness of the lower respiratory tract affecting
      infants that has considerable short and long-term morbidity and occasional
      mortality. It is the commonest cause of hospitalization for respiratory infection
      in early childhood, and the seasonal nature of the illness places considerable
      strain on health care resources during the bronchiolitis season. The youngest
      infants and those with preexisting cardiorespiratory disease are particularly at
      risk of severe illness. The treatment of infants with bronchiolitis is largely
      supportive. There are no therapies that have been proven to reduce the length of
      the hospitalization or intensive care stay. This paper will review the clinical
      course of bronchiolitis and discuss the aerosolized therapies that have been
      proposed for its treatment.

PMID- 12184861
TI  - Aerosolized vasodilators in pulmonary hypertension.
AB  - Pulmonary hypertension is a life-threatening disease characterized by an increase
      in artery pressure and vascular resistance in the pulmonary circulation. A
      primary form of pulmonary hypertension with unknown causes is to be distinguished
      from the far more frequent secondary forms based on known pulmonary and
      extrapulmonary disorders. An imbalance in the synthesis of vasoconstrictive and
      vasodilative agents seems to play an important role in the etiology of pulmonary
      hypertension. This pathophysiological background offers the possibility to
      develop treatment strategies, including application of vasodilative drugs. The
      intravenous administration of vasodilative agents, however, lacks pulmonary
      selectivity leading to systemic side effects. Therefore, the application of
      aerosol techniques for alveolar deposition of vasodilatory drugs was proposed and
      several studies with inhaled iloprost, a stable prostacyclin analogue,
      demonstrated preferential vasorelaxation in the pulmonary circulation, with the
      maximum pulmonary vasodilatory potency corresponding to that of intravenous
      prostacyclin. Clinical experiences with long-term inhaled iloprost are available
      showing sustained effects on exercise capacity and pulmonary hemodynamics in
      patients with pulmonary hypertension. Due to the necessary frequent inhalations
      (up to 12 times a day) and the potency of the prostaglandins, the choice of the
      nebulizer is critical, requiring physical characterization and device comparison
      studies under the right heart-catheter conditions. The concept of aerosolized
      vasodilators is meanwhile well established and offers a promising perspective in
      the treatment of pulmonary hypertension.

PMID- 12184862
TI  - Airway hyperresponsiveness: using bronchial challenge tests in research and
      management of asthma.
AB  - Bronchial challenge tests have been standardized in detail during the past two
      decades. They are providing relevant pathophysiological and clinical information
      about patients with asthma or chronic obstructive pulmonary disease (COPD), by
      allowing the measurement of the degree of airway hyperresponsiveness, which
      includes an increased sensitivity as well as increased maximal response to
      bronchoconstrictor stimuli. There are various types of challenges, to which the
      responses are not interchangeable. Responses to so-called "indirect" challenges
      are largely dependent on the state of activation of inflammatory or resident
      cells within the airways, and the state of activation can vary rapidly, either
      spontaneously or through intervention. Responses to "direct" challenges are
      dependent on less variable, rather chronic features of airways inflammation or
      remodeling. Bronchoprovocation tests provide integrated information about
      multiple pathophysiological pathways within the airway. This is in contrast to
      the measurements of cells, mediators, or cytokines in biological fluids, which
      provide only very specific information on selected inflammatory pathways. It has
      recently been shown that the outcome of asthma can substantially be improved when
      long-term treatment is not only guided by symptoms and lung function, but also by
      the degree of airway hyperresponsiveness to direct stimuli. Taken together,
      current data warrant a broader usage of bronchoprovocation tests in the research
      as well as clinical management of asthma and COPD. In asthma, it allows
      selective, individually targeted therapy of the patient as opposed to the
      currently recommended regimens that are (increasingly) unselective in their
      approach. The potential benefits of monitoring other phenotypic disease markers
      is currently under investigation.

PMID- 12184863
TI  - Drug absorption by the respiratory mucosa: cell culture models and particulate
      drug carriers.
AB  - The inhalation route is of increasing interest for both local and systemic drug
      delivery, including macromolecular biopharmaceuticals, such as peptides,
      proteins, and gene therapeutics. In addition to appropriate aerosolization for
      deposition in relevant areas of the respiratory tract, therapeutic molecules may
      require an advanced carrier system for safe and efficient delivery to their
      target. Two approaches to obtain novel carrier systems for pulmonary drug
      delivery are large porous microparticles with a low aerodynamic diameter and
      lectin-functionalized liposomes. Epithelial cells of alveolar or bronchial
      origin, obtained either from patient material or from established cell lines, can
      be grown on permeable filter supports, resulting in polarized monolayers with
      functional intercellular junctions. With such in vitro models, transport of drugs
      into pulmonary epithelial cells and/or across the air-blood barrier, as well as
      the effect and efficacy of novel drug carrier systems can be systematically
      studied.

PMID- 12184865
TI  - Novel instrumentation for the characterization of ultrafine particles.
AB  - Techniques for the in situ characterization of ultrafine particles are often
      based on the interaction of the particles with the surrounding gas or with light.
      Approaches that allow a fast determination of properties as size, mass, and
      surface are discussed here. As carbon is an important component of combustion
      particles, one of the most important and abundant part of anthropogenic ultrafine
      particles, techniques to determine elemental carbon concentration are also
      discussed; these methods are based on measuring optical absorption. Besides the
      analysis itself, sampling and pretreatment (e.g., dilution) play a very important
      role in obtaining reliable results.

PMID- 12184864
TI  - Leukocyte elastase inhibition therapy in cystic fibrosis: role of glycosylation
      on the distribution of alpha-1-proteinase inhibitor in blood versus lung.
AB  - Cystic fibrosis patients demonstrate an increased susceptibility to bacterial
      lung infections. Airway infiltration by neutrophils will then lead to an increase
      in human leukocyte elastase (HLE) within the extracellular compartment, thereby
      producing deleterious effects. Here, we investigated the properties and tissue
      distribution of an unglycosylated, recombinant form of the HLE inhibitor alpha-1
      proteinase inhibitor (alpha(1)-antitrypsin rhalpha1PI) when it is administered to
      the airway surface. We produced rhalpha1PI using a bacterial expression system
      and found the purified protein to be indistinguishable from blood-purified,
      glycosylated alpha1PI at inhibiting elastase in vitro. In contrast to intravenous
      administration, direct delivery of either alpha1PI or rhalpha1PI to the airway
      surface of CD-1 mice by nasal instillation produced similar highly detectable
      levels of protein in bronchoalveolar lavage at all time points, suggesting that
      glycosylation of alpha1PI does not play the same critical role in determining
      protein stability at the respiratory surface as it does in the vascular
      compartment. Interestingly, this unglycosylated rhalpha1PI was also highly
      protective against elastase-mediated injury 24 h after rhalpha1PI instillation
      and was consistently found to be significantly more protective than glycosylated
      blood-derived alpha1PI. Thus, these results provide evidence that aerosol
      delivery of rhalpha1PI could be an effective strategy for controlling HLE
      dependent pathophysiology associated with cystic fibrosis lung disease.

PMID- 12184866
TI  - The role of airway dendritic cell populations in regulation of T-cell responses
      to inhaled antigens: atopic asthma as a paradigm.
AB  - Chronic atopic asthma in adulthood represents the end stage of a disease process
      that is initiated during the perinatal period, when the naive immune system is
      first confronted with potentially allergenic airborne antigens. The initial phase
      involves compartmentalization of immunological memory into either the T-helper
      (Th)-1 or Th2 cytokine phenotypes, in atopic and nonatopics, respectively, and in
      a subset of atopics, this results in chronic Th2 cytokine-driven inflammation in
      the airways. Dendritic cells appear to play a key role in directing the memory
      generation process, and in subsequently controlling the intensity and duration of
      the ensuing Th-cell responses responsible for this inflammation.

PMID- 12184867
TI  - Size distributions of 3-100-nm urban Atlanta aerosols: measurement and
      observations.
AB  - Size distributions of urban Atlanta, Georgia, aerosols (0.003-2 microm) were
      measured from August 1, 1998 through August 30, 2000 as part of the Aerosol
      Research Inhalation Epidemiology Study (ARIES). Size distributions were measured
      five times per hour, and approximately 50,000 size distributions were measured
      during the 25-month study. This paper focuses on salient features of the sub-100
      nm data. We examine concentrations of particles in six equally spaced logarithmic
      intervals and show that particles of different sizes have distinctly different
      behaviors. For particles between 10 and 100 nm, average concentrations tended to
      be highest during winter, during rush hour, and on week days. Concentrations of
      particles in the 3-10-nm range were elevated in the summer due to photochemically
      driven nucleation, and also during winter. We hypothesize that the elevated
      wintertime concentrations of these particles were associated with nucleation that
      occurs as vehicular emissions mix with the cool ambient air. In any given size
      range, distributions of concentrations tend to be lognormal, but significant
      deviations from lognormality were occasionally observed. For particles in the 3.2
      5.6-nm diameter range, deviations were apparent in the summer when very high
      concentrations (up to 10(6) cm(-3)) were produced by photochemically driven
      nucleation. During 2 months of the study, deviations from lognormality for
      particles in the 32-56-nm diameter range occurred when anomalously high
      concentrations of 40-nm particles were observed.

PMID- 12184868
TI  - Targeting delivery of aerosols to different lung regions.
AB  - With the increasing use of aerosolized drugs, there is a need to understand the
      means by which these drugs can most effectively be targeted to desired regions of
      the lung. Several attempts have been made at targeting aerosols in the lung by
      changing particle sizes and breathing patterns with varying degrees of success.
      Recent use of such techniques as shallow, aerosol bolus delivery and extremely
      slow inhalations of aerosols in diagnostic lung tests may also prove beneficial
      for targeting drug delivery to the conducting airways. This review discusses the
      potential for utilizing aerosol delivery techniques for selectively targeting
      aerosol deposition along both serial and parallel pathways in the lung. Based on
      a review of previous studies concerning factors that determine aerosol and gas
      distribution in the lung, the potential for utilizing various breathing
      techniques in concert with variations in particle sizes are considered. Further
      research on the factors that determine distribution of aerosol in the diseased
      lung may help in designing successful targeting strategies for the future.

PMID- 12184869
TI  - Epidemiological evidence on health effects of ultrafine particles.
AB  - Evidence from epidemiologic studies linking ambient concentrations of particulate
      matter to morbidity and mortality influenced the guidelines for air quality
      standards worldwide. With the improvement of measurement techniques, clearer
      effects were observed with smaller particle sizes. Based on these effects and
      results from animal studies on the potential toxicity of ultrafine particles,
      recent epidemiologic studies focus on the health effects of particles which are
      less than 100nm in diameter. However, most of the studies are ongoing and only
      few results have been available so far. Six panel studies with patients suffering
      from chronic pulmonary diseases have been performed in Germany, Finland and the
      United Kingdom. Overall, a decrease of peak expiratory flow (PEF) and an increase
      of daily symptoms and medication use was found for elevated daily particle
      concentrations. Effects were seen with both fine and ultrafine particles. One
      large study on daily mortality from Germany showed comparable effects of fine and
      ultrafine particles in all size classes considered. However, fine particles
      showed more immediate effects while ultrafine particles showed more delayed
      effects on mortality. The limited number of epidemiological studies suggest that
      there are health effects of fine and ultrafine particles which might be
      independent of each other. If these effects are confirmed by ongoing research,
      monitoring and regulation of particulate air pollution may need to be revised.

PMID- 12184870
TI  - Formation and decomposition of hazardous chemical components contained in
      atmospheric aerosol particles.
AB  - Air particulate matter contains a wide range of substances, some of which pose a
      threat to human health. Chemical reactions occurring on aerosol particles in the
      atmosphere can transform hazardous components and increase or decrease their
      potential for adverse health effects. Especially organic compounds react readily
      with atmospheric oxidants, and since fine aerosol particles have a high surface
      to-volume ratio, their chemical composition can be efficiently changed by
      interaction with trace gases such as ozone and nitrogen oxides. In this paper the
      concepts required to understand and describe the formation and decomposition of
      hazardous chemical components contained in atmospheric aerosol particles are
      outlined. The processes at work on a molecular level in the chemical
      transformation of atmospheric particle components are illustrated for soot and
      polycyclic aromatic compounds (PACs), in particular for benzo[a]pyrene (BaP)
      which is one of the most prominent hazardous pollutants in the class of
      polycyclic aromatic hydrocarbons (PAHs). Recent results on the reaction kinetics
      and mechanisms of BaP degradation by ozone and nitrogen dioxide are presented.
      These results indicate faster degradation by atmospheric oxidants than previously
      estimated, which implies a higher potential for sampling artifacts and
      underestimation of the actual atmospheric abundance of BaP and other PAHs. Thus
      human exposure close to the sources of these compounds such as busy roadways may
      be significantly higher than previously assumed.

PMID- 12184871
TI  - The pulmonary toxicology of ultrafine particles.
AB  - Ultrafine particles are a component of air pollution, derived from primary
      combustion sources, and so we have undertaken a programme of study on the
      mechanisms of lung injury caused by ultrafine particles. Ultrafine particles made
      of low-solubility, low-toxicity materials are more inflammogenic in the rat lung
      than fine respirable, particles made from the same material. Ultrafine particles
      can cause inflammation via processes independent of the release of transition
      metals, as shown by the fact that soluble products from ultrafine carbon black
      have no ability to cause inflammation. The property that drives the greater
      inflammogenicity of ultrafines is unknown but very likely relates to particle
      surface area and involves oxidative stress. Increases in intracellular Ca(++) may
      underlie the cellular effects of ultrafines, although the mechanism whereby
      ultrafines have this effect is not understood. However, increased influx of
      Ca(++) into macrophages occurs via the membrane Ca(++) channels following contact
      with ultrafine particles, and involves oxidative stress. Increased Ca(++) in
      macrophages exposed to ultrafines can lead to the transcription of key pro
      inflammatory genes such as TNFalpha. Ultrafine particles can also impair the
      ability of macrophages to phagocytose and clear other particles, and this may be
      pro-inflammogenic.

PMID- 12184872
TI  - Intranasal immunization against influenza.
AB  - Nasalflu is a novel influenza subunit vaccine, which is administered by the
      intranasal route using a spray device. Nasalflu is based on the virosomal concept
      which is registered in the EU as Epaxal Berna, a vaccine against Hepatitis A, and
      Inflexal Berna V, a subunit influenza vaccine. The virosome is a carrier system
      which delivers antigens to cells and is able to induce both B- and T-cell
      immunity. When virosomal vaccines are given parenterally, an immune response is
      elicited fast and sufficiently.

PMID- 12184873
TI  - Gene therapy for cystic fibrosis by means of aerosol.
AB  - Gene therapy by aerosol is an attractive approach for the treatment of cystic
      fibrosis (CF). Clinical trials with aerosols in CF patients have been conducted
      by five different groups, three using adenoviral vectors and two using cationic
      liposomes carrying the coding sequence for the Cystic Fibrosis Transmembrane
      Conductance Regulator (CFTR). These trials revealed that gene transfer from the
      lumen to the respiratory epithelium can currently be achieved in vivo, but only
      with low efficiency and for limited duration. Some of the many hurdles on the way
      to successful gene therapy for this disease will be discussed in this review.
      Innovative strategies need to be developed to reach this tantalizing goal.

PMID- 12184874
TI  - Aerosol number concentrations and size distributions at mountain-rural, urban
      influenced rural, and urban-background sites in Germany.
AB  - Long-term aerosol measurements have been made at three sites in Germany,
      representing different levels of pollution: Hohenpeissenberg (mountain-rural),
      Melpitz (urban-influenced rural), and Leipzig (urban background). (Urban
      background aerosol represents a mixture of aerosols emitted in the city and
      aerosols transported into the city measured at a site with no direct emissions
      nearby.) To provide data that will allow better estimates of the influence of
      environmental aerosol particles on humans, we review diurnal variations of mean
      total number concentrations and size distributions of submicrometer environmental
      aerosol particles (including ultrafine particles smaller than 100 nm) for winter
      and summer periods in these three regions. Number concentrations and size
      distributions are compared and related to peak traffic periods and to
      meteorologically induced new-particle formation processes. The number
      concentration increase with increasing level of pollution. The mountain-rural
      site shows the smallest and the urban background site the highest number
      concentration. The relative diurnal variation of the number concentration between
      day and night, however, is for all sites nearly the same. Generally, traffic
      related number concentration during rush-hour periods peaks in the size range of
      20-30 nm. Due to weaker atmospheric convective processes in winter, this traffic
      related aerosol is more pronounced than that in summer. In summer,
      meteorologically induced new-particle formation processes add another number
      concentration peak to the aerosol near 10 nm. This peak occurs near noon,
      independent of the day of the week. For the mean number concentrations and size
      distribution, this new-particle formation process was only relevant for the urban
      influenced rural and the urban-background sites.

PMID- 12184876
TI  - The loss of a twin: theory and practice revisited. Proceeding of a symposium held
      at the International Congress on Twin Studies. London, United Kingdom. July 2001.

PMID- 12184877
TI  - Twin research. Introduction.

PMID- 12184879
TI  - Panel discussion. Grief and bereavement with the loss of a twin.

PMID- 12184881
TI  - The Yoruba's cultural perspective of death with special reference to twins.
AB  - To the Yoruba people of South-West Nigeria, on the West Coast of Africa, death,
      or transition from one level of existence to another, is well accepted as part of
      life. Rites of passage are seen as an opportunity for saying farewell to the
      deceased and seeking their continuous protection of the living members of the
      families. After the death of a twin, a twin statuette, symbolically representing
      the departed twin, also acts as a companion and solace to the living twin. This
      paper examines these subjects including the special rites performed for twins,
      the relationship of the family to the deceased and the question of reincarnation

PMID- 12184882
TI  - How mothers cope with the death of a twin or higher multiple.
AB  - Estimates suggest up to 15% of multiples grow up as singleton survivors. Few
      studies have reported how bereaved multiple birth mothers with a surviving
      multiple cope with their bereavement. Using the population-based Western
      Australian Twin Child Health study database and other sources, we interviewed 66
      bereaved mothers with at least one surviving multiple. For many, this contact was
      the first acknowledgement of their status as multiple birth mothers since their
      loss. The Beck Depression Inventory 2nd Edition (BDI) showed significant
      reduction in depression between the time of loss and our interview. For mothers
      as a group there was a high correlation between current and retrospective BDI,
      and retrospective BDI and all three Perinatal Grief Scales (PGS). There was a
      significant correlation between the three grief factors on the PGS. When
      subdivided, this held for mothers who suffered a loss at or before the neonatal
      period, but not for those whose loss occurred later. Bereaved mothers of
      multiples scored significantly higher on the PGS than the PGS norm for bereaved
      mothers of singletons, which we attribute to others not acknowledging their
      grief, and/or recruitment differences. There were no significant differences in
      PGS scores related to cause, the time since death, or sibling number or age.
      Spiritual beliefs and finding meaning in loss were positively related to scores
      for adjustment and acceptance. Although traumatised, most mothers accommodated
      their losses meaningfully in their lives. Their own support recommendations are
      included.

PMID- 12184883
TI  - The context and long-term impacts of multiple birth loss: a peer support network
      perspective.
AB  - Following my own experience with the death of a twin baby, I founded the Center
      for Loss in Multiple Birth (CLIMB) Inc. During the last 13 years I have worked
      with nearly 7000 bereaved parents of twins, triplets or other high multiples
      throughout the US and worldwide. The role of a peer support organisation and the
      range of families with multiples who have contacted it is described. They come
      from diverse backgrounds with many forms of bereavement: death during pregnancy,
      at birth or after of both or all babies, of one twin, of one or more higher order
      multiples; multifetal pregnancy reduction or selective fetocide; the death of one
      or more multiples in childhood. Some have had more than one multiple pregnancy
      and loss. Many are concerned for the surviving children. A peer support
      organisation has an important role to play in increasing public awareness of the
      needs of these families as well as influencing policy on infertility treatments
      that carry a high risk of producing multiple pregnancies with the associated risk
      of death and disability for one or more of the babies.

PMID- 12184884
TI  - Loss in higher multiple pregnancy and multifetal pregnancy reduction.
AB  - From early pregnancy into childhood, higher multiples have much higher rates of
      mortality, whether from spontaneous abortion, the 'vanishing twin' syndrome,
      fetal or infant death. Many parents must cope with the death of one baby whilst
      the siblings remain critically ill or later become disabled and yet there grief
      is often underestimated. Little is known about the long term feelings of parents
      who choose to have a multifetal pregnancy reduction (MFPR). Most say they made
      the right decision but also that there was insufficient respect for their loss.
      They are often anxious about what, if anything, to tell the survivors and how
      they might react. Long term follow-up studies of the children as well as the
      parents are needed. Meanwhile parents who chose to have a MFPR must be given more
      information and ongoing support.

PMID- 12184885
TI  - Psychobiological and evolutionary perspectives on coping and health
      characteristics following loss: a twin study.
AB  - An analysis of coping, grief and health characteristics is reported for a
      bereaved monozygotic (MZ) and dizygotic (DZ) same-sex twin sample. The data were
      examined with reference to psychobiological and evolutionary perspectives on
      behavior. A Coping Scale, included as part of a comprehensive Twin Loss Survey
      (TLS), assessed coping with daily responsibilities and activities 1-2 months
      before the co-twin's death, 1-2 months following the co-twin's death and
      currently. A Grief Intensity Scale obtained judgments of grief 1-2 months
      following the loss, and currently. Information on physical symptoms was available
      from the Somatization Scale of the Grief Experience Inventory. Psychobiological
      and evolutionary perspectives specified hypotheses for two twin groups: one model
      was specified to reflect bereavement experiences immediately following loss of
      the co-twin (retrospective twin group); a second model represented present
      bereavement response (current twin group). Consistent with psychobiological
      theory, twins' social closeness showed a positive association with grief
      intensity which, in turn, affected somatic symptoms and coping efficacy in
      predicted directions. With respect to evolutionary psychological theory, the
      effect of zygosity on current grief implicated correlates of genetic relatedness
      as factors in the bereavement process.

PMID- 12184886
TI  - Monozygotic and dizygotic twins' retrospective and current bereavement-related
      behaviors: an evolutionary perspective.
AB  - The present study compared bereavement responses of 325 monozygotic (MZ) and 176
      dizygotic (DZ) adolescent and adult twins following the loss of their co-twins. A
      subset of twins completed the Grief Experience Inventory using a retrospective
      time frame, while a second subset completed it using a current time frame. It was
      hypothesized that MZ twins (in both retrospective and current groups) would
      report higher levels of grief-related behavior than DZ twins, consistent with
      Hamilton's (1964) concept of inclusive fitness. Discriminant function and profile
      analyses yielded supportive findings, but only for the retrospective MZ and DZ
      twin comparisons. Females in both groups expressed higher levels of bereavement
      related behavior than males. Findings are discussed with reference to theoretical
      aspects of grief and mourning.

PMID- 12184887
TI  - Twin death and mourning worldwide: a review of the literature.
AB  - Cultural beliefs about the nature of multiples appear in the mourning practices
      of many civilizations. Ethnographic literature suggests common themes that echo
      modern concepts. Many societies viewed twins as fragile, likely to die without
      preferential or meticulously equal treatment. A shared soul between twins is a
      common tenet, and the death of one is often felt to herald the other's prompt
      demise. The close relationship between multiples influences funerary rites.
      Honor, fear and mysticism are often evident in rituals. Twin infanticide was
      widely practiced, yet mourning customs were still observed. Many peoples
      recognize the special status of multiples and their families after one, two or
      more die.

PMID- 12184888
TI  - Comments on and extracts from: the death of a twin: mourning and anniversary
      reactions - fragments of 10 years of self-analysis by George Engel.
AB  - Only recently has the special bereavement associated with the loss of a twin been
      generally recognised. With the notable exception of Joan Woodward, few have
      written on the subject. We, therefore, offer a shortened version of a paper
      written nearly 30 years ago. George Engel was himself a lone twin as well as
      being an eminent psychiatrist and psychoanalyst in the United States. The length
      of the paper precludes reprinting the totality but we hope readers will be
      encouraged to seek out the original published in The International Journal of
      Psycho-analysis in 1975, Vol 56 part 1, 23-40.

PMID- 12184889
TI  - The effect of losing the twin and losing the partner on mortality.
AB  - Several studies have explored the impact of marital bereavement on mortality,
      while increasing emphasis has recently been placed on genetic factors influencing
      longevity - in this paper, we study the impact of losing the spouse and losing
      the co-twin, for twins aged 50 to 70. We use data from the Danish Twin Registry
      and the Population Register of Denmark for the period 1968 through 1999. Firstly,
      we use survival analysis to study mortality after the death of the spouse or the
      co-twin. We find that the risk of dying is highest in the first year after the
      death of the spouse, as well as in the second year after the death of the co
      twin. We then use event history analysis techniques to show that there is a
      strong impact of the event 'losing the co-twin' even after controlling for age,
      sex and zygosity and that this effect is significantly higher in the second year
      of bereavement. The effect is similar for men and women, and it is higher for
      monozygotic twins. The latter confirms the influence of genetic factors on
      survival, while the mortality trajectory with a peak in the second year after the
      death of the co-twin is consistent with the existence of a twin bereavement
      effect.

PMID- 12184890
TI  - Bereavement in twin relationships: an exploration of themes from a study of
      twinship.
AB  - The primary foci of twin research have been on twins as a biological phenomenon,
      on the management of medical complications of twin pregnancy and birth and on the
      study of individual differences and development by psychologists and geneticists
      for whom twins provide a powerful research tool. The twin relationship - twinship
      - has received less research attention, including the aspect of bereavement which
      may occur at any stage of life. This paper presents some findings from a
      qualitative study that used grounded theory methodology to explore the nature of
      twinship especially issues relevant to psychological counselling with twins.
      Fourteen participants were interviewed in-depth about their understanding and
      experience of twinship. Participants were selected who had a rich knowledge and
      experience of twinship and of therapeutic work. Segments of transcribed
      interviews were constantly compared to describe and elaborate frequently repeated
      concepts in the data. Two of the main themes of discernment, the core category of
      the theory of twinship, are described. These are 'defining boundaries' and
      'managing ambiguity'. Aspects of these as experienced by twins are discussed in
      the light of current psychological theories about bereavement.

PMID- 12184891
TI  - Coping with twins discordant for intellectual disabilities: the mothers' view.
AB  - In this exploratory study of 15 families with a twin-pair, of which one has an
      intellectual disability, the Nijmegen Questionnaire on Childrearing Situations
      (NQCS) was used to ask mothers about their perceptions and experiences of
      parenting. An interview with the mothers was done to understand the initial
      stages of coping with this double problem: educating a twin-pair and a child with
      an intellectual disability. Four groups of mothers were identified, depending on
      whether they accepted the intellectual disability of their child and/or whether
      they perceived their children as a twin-pair or not. Finally, some critical
      questions for further research and management were formulated.

PMID- 12184892
TI  - We didn't deserve this: bereavement associated with multifetal reduction.
AB  - With the dramatic increase in the incidence of higher-order multiple pregnancies,
      more and more women are advised to consider undergoing multifetal reduction.
      However, little is known about the woman's experience of making the decision to
      undergo or forgo reduction. This study explored the experiences of seven women in
      making this decision and to identify any effects of it. Vivid descriptions
      emerged of multiple levels of bereavement. Several participants lamented that
      nothing occurred naturally in their pregnancies, from conception right through
      delivery and life with multiples.

PMID- 12184893
TI  - Personal experiences of bereaved twins, parents of twins, and their carers.
AB  - We invited bereaved twins, parents of twins and carers to describe some of their
      personal experiences. We are grateful to all of them for their brave candour. We
      gave extra space to Kathy's story about the impacts of the loss of her own twin
      because it vividly illustrates the profound connections twinship can generate.
      Similarly we thought the cruelly long and complex saga of the life and death of
      Maxine's twins could help understanding of the distressing repercussions that
      often attend the low birth weight and prematurity that are so common amongst
      multiple births.

PMID- 12184899
TI  - Computer-assisted laparoscopic splenectomy with the da Vinci surgical robot.
AB  - Laparoscopic splenectomy has become the standard of care for the surgical
      treatment of idiopathic thrombocytopenic purpura (ITP). The minimally invasive
      approach to splenic disorders such as ITP clearly results in the same benefits to
      the patients as have been demonstrated with the laparoscopic cholecystectomy
      techniques. New technologies in minimally invasive surgery have resulted in the
      development of robotic devises that assist the surgeon during the procedures.
      Robotic surgery is in its infancy at this point in time. Herein, we report a
      splenectomy performed with the assistance of the da Vinci surgical robot. With
      advancement of technology, robotic systems will play an integral role in future
      minimally invasive surgery.

PMID- 12184900
TI  - Laparoscopic repair of a Morgagni hernia presenting with syncope in an 85-year
      old woman: case report and update of the literature.
AB  - An 85-year-old woman was transferred from her local hospital for cardiac
      evaluation after presenting with repeated episodes of syncope during bowel
      movements. A thorough evaluation revealed no cardiac abnormalities but did reveal
      a Morgagni hernia with transverse colon in the mediastinum. She underwent
      laparoscopic reduction of the colon and repair of the hernia with mesh and had a
      rapid and uneventful recovery.

PMID- 12184901
TI  - Training in laparoscopic suturing skills using a new computer-based virtual
      reality simulator (MIST-VR) provides results comparable to those with an
      established pelvic trainer system.
AB  - BACKGROUND: We hypothesized that the Minimally Invasive Surgery Trainer (MIST-VR;
      VP Medical R, London, U.K.) would be as effective as the Yale Laparoscopic Skills
      Course in improving laparoscopic intracorporeal suturing skills. MATERIALS AND
      METHODS: Each student made six attempts to tie a knot laparoscopically. Students
      were then randomized to train on the MIST-VR for five sessions (six
      skills/session) or the Yale Skills for five sessions (three skills/session) over
      5 days. On completion of training, all students were evaluated by a test
      consisting of six attempts to tie a laparoscopic knot. RESULTS: The percentage
      improvement in knot tying time did not differ significantly in the pelvic trainer
      group (30 +/- 21%) (from 443 +/- 135 to 311 +/- 137 seconds) and the MIST-VR
      group (39 +/- 21%) (from 409 +/- 109 to 256 +/- 140 seconds) (P = 0.308).
      CONCLUSIONS: The MIST-VR is equivalent to the Yale Skills Course for training in
      the advanced laparoscopic skill of intracorporeal suturing.

PMID- 12184903
TI  - Central neck lymph node removal during minimally invasive video-assisted
      thyroidectomy for thyroid carcinoma: a feasible and safe procedure.
AB  - BACKGROUND AND PURPOSE: In 1998, we developed a technique for video-assisted
      thyroidectomy (VAT) which we proposed using also in patients with small low-risk
      papillary thyroid carcinomas (PTC). In some cases, enlarged lymph nodes are
      incidentally found at surgery for PTC. These nodes should be removed because of
      the risk of metastases. In this paper, we report on the patients in whom we
      removed enlarged central neck lymph nodes during VAT for PTC and discuss the
      feasibility and safety of video-assisted central neck lymph node dissection
      (VALD). PATIENTS AND METHODS: The procedure is performed by a totally gasless
      video-assisted technique through a single 1.5-to 2.0-cm skin incision above the
      sternal notch. Dissection is performed under endoscopic vision using a technique
      very similar to that of conventional surgery. Only enlarged lymph nodes were
      removed and sent for frozen section examination (FS). No other dissection was
      performed in case of negative FS. Five patients underwent VALD during VAT for
      PTC. RESULTS: The mean number of lymph nodes removed was 2.4. No metastases were
      found at FS or final histology examination. Postoperative complications included
      two transient postoperative hypocalcemias. No evidence of residual or recurrent
      disease was observed at postoperative follow-up. The cosmetic result was
      excellent. CONCLUSION: Our experience demonstrates that removal of central
      compartment lymph nodes is feasible and safe. Perhaps also complete central neck
      lymph node dissection can be performed. Some doubts persist about the oncologic
      validity of this approach. For definitive conclusions, larger series and
      comparative studies are necessary.

PMID- 12184902
TI  - Laparoscopic lymph node dissection using ultrasonically activated shears:
      comparison with electrosurgery.
AB  - PURPOSE: To assess and compare perioperative parameters in two groups of patients
      treated by different laparoscopic techniques of lymph node dissection (LND) for
      gynecologic cancer. PATIENTS AND METHODS: Between April 1996 and March 2001, 59
      consecutive women with microinvasive cervical cancer (N = 5) or clinical stage I
      endometrial cancer (N = 54) underwent laparoscopic LND during a primary staging
      procedure using an electrosurgery (ELC) or ultrasonic (US) operative technique.
      The two groups were compared for perioperative outcomes. Differences between the
      two groups were determined by the Wilcoxon's rank-sum test. RESULTS: Laparoscopic
      LND and other staging procedures were completed successfully in 58 women (98.3%).
      There were no statistically significant differences between the groups with
      regard to perioperative outcomes (operation time, time for LND, blood loss,
      hospital stay, complications), but there was a significant difference (P =
      0.0008) in the number of lymph nodes harvested: a mean of 13.7 in the ELC group
      and 17.5 in the US group. The pathologists found that the reading of histology
      slides was easier after US dissections because of the greater depth of thermal
      injury in the lymphatic tissue in ELC group. CONCLUSION: The US operative
      technique ensures efficient coagulation, cutting, dissection, and grasping for
      laparoscopic LND in patients with cervical and endometrial cancer.

PMID- 12184904
TI  - Laparoscopic tube cholecystostomy: still useful in the management of complicated
      acute cholecystitis.
AB  - The preferred treatment for acute cholecystitis is laparoscopic cholecystectomy.
      Conversion to open operation may be necessary in cases where the anatomy is
      unclear or complications are encountered. Laparoscopic tube cholecystostomy
      remains an alternative to open surgery in cases where the gallbladder is judged
      too inflamed to allow for laparoscopic removal and in cases where the patient is
      too sick to tolerate a more extensive procedure. It also provides access for
      diagnostic cholangiography. We report three patients with acute cholecystitis who
      underwent laparoscopic cholecystostomy and interval laparoscopic cholecystectomy
      without complications. Laparoscopic tube cholecystostomy is safe and remains a
      useful option in select patients with complicated acute cholecystitis.

PMID- 12184905
TI  - Effect of timing of surgery, type of inflammation, and sex on outcome of
      laparoscopic cholecystectomy for acute cholecystitis.
AB  - BACKGROUND AND PURPOSE: Studies have shown the safety and effectiveness of
      laparoscopic cholecystectomy (LC) for acute cholecystitis (AC). Our aim was to
      establish the outcome of LC in patients with AC on the basis of duration of the
      attack before surgery took place, the type of gallbladder inflammation, and
      patient sex. PATIENTS AND METHODS: All 204 patients at Princess Basma Teaching
      Hospital who underwent LC for AC by the authors between September 1994 and June
      1999, were retrospectively reviewed. They were categorized into Group I, where
      surgery took place within 72 hours of the acute attack (N = 78; 54 women and 24
      men), and Group II, if later than that (N = 126; 70 women and 56 men).
      Gallbladder pathology was classified as gangrenous, empyema, edematous, mucocele,
      or AC along with contracted fibrosed gallbladder. RESULTS: Conversion to open
      cholecystectomy was needed in 12% of the total series. In Group I, 3.8% of the
      patients needed conversion compared with 16.7% in Group II patients (P = 0.01).
      Also, 4% of the female patients needed conversion compared with 24% of the male
      patients (P = 0.000). There was an association between the pathological type of
      AC and the likelihood of conversion (P = 0.002), conversion being least common in
      those with mucocele and most common in those with empyema and gangrene. The
      median operation time was 75 +/- 36 minutes, but the operation time for Group II
      patients was significantly longer (P = 0.001) than in Group I patients. Operation
      time in the male patients was significantly longer than in the female patients (P
      = 0.000). There was no statistically significant difference in the duration of
      hospital stay in the two groups or in men and women. There were no deaths or main
      bile duct injuries in the series. In successful LC, missed stones occurred in
      3.3% of the patients. Bile collection, which was treated by open surgery,
      developed in one female patient. CONCLUSION: Laparoscopic cholecystectomy is a
      reliable and safe modality for the management of AC. It was not associated with
      an increased incidence of bile duct injury in this series. It should be the first
      choice before resorting to open surgery. Factors associated with increased
      conversion include delay in surgery of more than 3 days from the acute attack and
      certain pathology, with conversion being more likely in empyema. Conversion also
      was more likely in male patients.

PMID- 12184906
TI  - Esophageal variceal bleeding secondary to portal hypertension: endoscopic
      sclerotherapy as the first-step treatment.
AB  - BACKGROUND: Variceal bleeding from the esophagus is an important cause of
      mortality and morbidity in children with portal hypertension (PHT). PATIENTS AND
      METHODS: A series of 69 PHT cases (41 intrahepatic, 28 extrahepatic) have been
      evaluated in our department since 1990. According to the Child-Pugh
      classification, 49 cases were in class A, 16 cases were in class B, and 4 cases
      were in class C at admission. In our protocol, endoscopic sclerotherapy is
      performed in all patients, and the diagnosis is achieved directly by diagnostic
      laparoscopy and fine-needle liver biopsy. The procedure is applied under general
      anesthesia, and 1% aethoxysclerol (polidocanol) is injected paravariceally and
      intravariceally with the use of a flexible endoscope. RESULTS: The Sugiura
      procedure was performed in nine patients who presented with recurrent bleeding
      episodes despite the strict sclerotherapy protocol. Liver transplantation was
      performed in two patients who were in Child class C. The total mortality rate in
      this series was 7% (5/69). CONCLUSION: Endoscopic sclerotherapy, as presented
      herein, decreases the need for additional surgical interventions in children with
      PHT.

PMID- 12184907
TI  - Umbilical stalk technique for establishing pneumoperitoneum.
AB  - The Veress needle technique for establishing pneumoperitoneum is widely used yet
      associated with slow insufflation and potentially life-threatening complications.
      The open or Hasson technique is relatively safer but considered cumbersome by
      many. We describe a mini-open technique that uses a 5-mm transumbilical incision
      and placement of a 5-mm blunt cannula without the trocar. We have employed this
      technique for 4 years in 600 patients without a midline laparotomy incision
      incorporating the umbilicus and have accessed the abdomen safely for laparoscopy
      without any complications. The time from skin incision to the start of the
      procedure is usually under 2 minutes. Our umbilical stalk technique provides
      rapid and safe access to the abdomen, eliminating the dangers of a blind sharp
      needle or trocar insertion and the need for a larger incision with placement of
      stay sutures. We recommend this simple technique for entry into the uncomplicated
      abdomen.

PMID- 12184908
TI  - A technique for safe placement of a biliary endoprosthesis after laparoscopic
      choledochotomy.
AB  - BACKGROUND: Biliary endoprosthesis has been proposed as an alternative to T-tube
      placement after laparoscopic choledochotomy in an attempt to eliminate the
      complications associated with T-tubes. Biliary endoprostheses have been, until
      now, placed under fluoroscopic guidance. We present a modification of Gersin's
      method for endoprosthesis placement under direct vision. PATIENTS AND METHODS: As
      of July 2001, seven patients who fulfilled the criteria for common bile duct
      (CBD) exploration through a choledochotomy, a biliary endoprosthesis was inserted
      under direct vision at the end of the procedure with primary closure of the CBD
      above it. In all cases, plastic biliary stents 10F in diameter were used ranging
      from 5 to 10 cm in length. We describe in detail the technique of CBD stent
      placement using the choledochoscope as the advancing device. We also propose the
      use of intraoperative cholangiography instead of on-table endoscopy to check the
      final correct position of the stent. RESULTS: The median postoperative hospital
      stay was 2 days. Two patients developed transient hyperamylasemia in the
      immediate postoperative period. None of the patients developed short-term
      complications (<30 days), namely bile leak, CBD erosion, stent occlusion, or
      stent migration. The long-term results revealed early return to full daily
      activities and normal liver function tests. Stents were removed endoscopically 4
      weeks after the initial procedure except in two patients who spontaneously passed
      them. CONCLUSION: We propose a 10F 10-cm biliary endoprosthesis placed under
      direct vision as a safe, effective, time-sparing, and cost-effective adjunct to
      CBD exploration through a choledochotomy. Placement of the endoprosthesis is
      associated with low morbidity and eliminates the complications related to T
      tubes.

PMID- 12184909
TI  - Splenectomy using a completely needlescopic procedure: report of three cases.
AB  - BACKGROUND AND PURPOSE: Needlescopic instruments are being used in various fields
      of endoscopic surgery. We evaluated the safety and efficacy of laparoscopic
      splenectomy using a needlescope. PATIENTS AND METHODS: This procedure was
      performed in three patients, two women and one man, having idiopathic
      thrombocytopenic purpura that had not responded to medical treatment. Four ports
      (one 12 mm and three 2 mm in diameter) were introduced into the left upper
      quadrant. A 2-mm needlescope was used throughout the procedure. The spleen was
      divided from the splenocolic, splenophrenic, and splenorenal ligaments posterior
      to the splenic hilum. The splenic hilar and short gastric vessels were divided
      simultaneously using a linear stapler. The resected spleen was morcellated via
      the 12-mm port. RESULTS: The mean operation time was 167 minutes, and the mean
      estimated blood loss was 70 mL. No postoperative analgesia was needed by any of
      the patients, and there were no perioperative complications. The 2-mm
      postoperative scars were virtually invisible. CONCLUSION: Needlescopic
      splenectomy for idiopathic thrombocytopenic purpura is feasible and safe with
      less postoperative pain and a superior cosmetic result compared with conventional
      laparoscopic splenectomy.

PMID- 12184910
TI  - Complete laparoscopic management of choledochal cyst: report of two cases.
AB  - BACKGROUND: Choledochal cyst is a rare congenital anomaly of the biliary tract.
      With increased familiarity with the laparoscopic anatomy of the biliary tract and
      advances in minimally invasive techniques, surgeons have ventured further to
      operate on technically difficult cases such as choledochal cyst that were until
      recently managed by laparotomy. PATIENTS AND METHODS: We present our experience
      with two female patients aged 14 years and 26 years with choledochal cyst (type I
      according to the Alonzo-Lej classification) that were successfully excised with
      construction of a Roux-en-Y hepaticojejunostomy entirely laparoscopically.
      RESULTS: Both patients had an uneventful recovery, with no major morbidity. The
      first patient had a bile leak, which resolved over 5 days. Both were discharged
      by the 5(th) postoperative day. CONCLUSION: Laparoscopic management of
      choledochal cyst is feasible although technically difficult and may be performed
      in specialized institutes dealing with advanced laparoscopic surgery.

PMID- 12184911
TI  - Transcription factor NF-IL6 (C/EBPbeta) activates the expression of the mouse MHC
      class I H2-Kb gene in response to TNF-alpha via the intragenic downstream
      regulatory element.
AB  - The 5'-enhancer-deleted genomic construct of the H2-K(b) gene, stably integrated
      into the genome of L(tk-) fibroblasts, retains full competence to be induced by
      tumor necrosis factor-alpha (TNF-alpha) treatment. The only defined regulatory
      region in this construct is the intragenic downstream regulatory element (H2DRE).
      Computational inspection uncovered two potential NF-IL6 (C/EBPbeta) binding
      motifs within the H2DRE. Chloramphenicol acetyltransferase (CAT) reporter gene
      assay revealed that NF-IL6 is able to elevate transcription from H2DRE. Moreover,
      transient transfection of an NF-IL6 expression vector increased both constitutive
      and TNF-alpha-induced mRNA levels of endogenous H2 class I genes, and
      transfection of an NF-IL6 dominant negative construct decreased the expression of
      endogenous H2 class I genes in a dose-dependent manner. Using the electrophoretic
      mobility shift assay (EMSA) and antibody supershift assay, we were able to
      qualify the two computationally identified NF-IL6 binding motifs as one high
      affinity and one low-affinity binding site. We conclude that the H2-K(b) gene
      belongs to target genes of the NF-IL6 (C/EBPbeta) in the course of the cellular
      response to TNF-alpha, and we discuss some consequences of this conclusion in a
      general framework of inducible expression of the H2-K(b) gene.

PMID- 12184912
TI  - Increased expression of interleukin-18 receptor on T lymphocytes in patients with
      acute graft-versus-host disease after allogeneic bone marrow transplantation.
AB  - Acute graft-versus-host disease (aGVHD), a potentially fatal side effect of
      allogeneic bone marrow transplantation (BMT), is initiated by the action of donor
      derived T lymphocytes. We have shown previously that aGVHD is associated with
      elevated serum levels of interleukin-18 (IL-18). In this study, we analyzed the
      expression of the IL-18 receptor (IL-18R) on T lymphocytes of BMT patients with
      aGVHD. Flow cytometric analysis showed that in healthy subjects, a small
      population of CD4+ T cells expressed IL-18Ralpha, whereas a relatively large
      population of CD8+ T cells expressed IL-18Ralpha. In aGVHD patients, there were
      marked increases in the proportion of CD4+ or CD8+ T cells that express IL
      18Ralpha. RT-PCR assays showed elevation of IL-18Ralpha and IL-18Rbeta mRNA
      levels in CD8+ T cells in aGVHD patients. These findings suggest that the
      expression of IL-18R is upregulated in T cells in patients with aGVHD and that
      the IL-18/IL-18R system is active during aGVHD.

PMID- 12184913
TI  - Interleukin-2 directly induces activation and proliferation of chicken T cells in
      vivo.
AB  - Cytokines, as immune activators, have been investigated in mammalian systems as
      natural adjuvants and therapeutics. In particular, interleukin-2 (IL-2) has been
      studied widely as a vaccine adjuvant and immuno-enhancer because of its role in
      activating T cell proliferation. We show here that the first nonmammalian IL-2
      gene cloned, chicken IL-2 (ChIL-2), exhibits similar biologic activities to those
      of mammalian IL-2. To assess the activities of ChIL-2 in vivo, we injected birds
      with recombinant ChIL-2 (rChIL-2) protein. rChIL-2 treatment induced peripheral
      blood lymphocytes to express cell surface IL-2 receptors (IL-2R) within 48 h and
      resulted in an increase in the proportion of peripheral blood CD4+ and CD8+ T
      cells. Using bromodeoxyuridine (BrdU) incorporation as a measurement of cell
      proliferation, we showed the increase in T cell populations to be due to cell
      proliferation. The ability of ChIL-2 to cause both activation and proliferation
      of T cells in vivo indicates that it has the potential to be used as an immune
      activator.

PMID- 12184914
TI  - Interleukin-1-mediated inhibition of cytomegalovirus replication is due to
      increased IFN-beta production.
AB  - Previous studies have demonstrated that the intercellular spread of
      cytomegalovirus (CMV) is reduced in marrow stromal cells that either secrete
      interleukin-1 (IL-1) or are treated with exogenous IL-1. Here, we report that IL
      1-treated marrow stromal cells and fibroblasts, when infected with CMV, produce
      decreased amounts of infectious progeny virus. CMV-infected cells treated with IL
      1 contained more interferon-beta (IFN-beta) mRNA at 24 h postinfection compared
      with untreated, infected cells. IFN-beta protein secreted into fibroblast culture
      supernatants increased from 46 +/- 1 IU/ml in untreated, infected cells to 116 +/
      5 IU/ml in IL-1-treated infected cells. When IFN-beta activity was inhibited,
      using blocking antibodies to either the cytokine or the IFN-alpha/beta receptor,
      the addition of IL-1 no longer limited viral spread. Furthermore, viral spread in
      nonIL-1-treated cultures was inhibited by the addition of recombinant IFN-beta.
      These studies suggest that IL-1 functions to limit CMV spread by increasing the
      expression of IFN-beta, which in turn reduces production of infectious virus.

PMID- 12184915
TI  - Discordant effect of IFN-beta1a therapy on anti-IFN antibodies and thyroid
      disease development in patients with multiple sclerosis.
AB  - Interferon-beta1b (IFN-beta1b) therapy is associated with a relatively high risk
      of developing thyroid disease. IFN-beta1a is regarded as less immunogenic than
      IFN-beta1b because of its structural homology to natural IFN-beta. We assessed
      the effect of 1 year of IFN-beta1a treatment on thyroid function and autoimmunity
      in 14 multiple sclerosis (MS) patients. The results were compared with those
      obtained in a series of 31 MS patients treated with IFN-beta1b. The prevalence of
      positive binding antibody (BAb) titer and neutralizing (NAb) anti-IFN antibody
      titer in the two groups was also assessed. The BAb and NAb positivity rate in IFN
      beta1a-treated patients was significantly lower than in the group submitted to
      IFN-beta1b therapy (7% vs. 84% and 0% vs. 30%, respectively). Although the
      incidence of thyroid dysfunction was slightly higher in IFN-beta1b-treated
      patients than in those undergoing IFN-beta1a treatment (33% vs. 23%,
      respectively), it did not reach statistical significance. Thyroid disease was
      unrelated to the presence of positive serum BAb or NAb titer in both the group
      undergoing IFN-beta1a therapy and in that treated with IFN-beta1b. In both
      groups, thyroid disease developed mostly in women (71%) against a background of
      preexisting thyroiditis and a diffuse hypoechoic ultrasound thyroid pattern
      (80%). IFN-beta1a treatment was associated with a significantly lower prevalence
      of both BAb and NAb-positive titers than was IFN-beta1b. Conversely, thyroid
      disease was similar and unrelated to the presence of positive anti-IFN-beta
      antibody titer. Therefore, routine thyroid assessment may be advised during IFN
      beta1a treatment, especially in patients with preexisting thyroiditis.

PMID- 12184916
TI  - IFN-beta gene transfer into the central nervous system using bone marrow cells as
      a delivery system.
AB  - The peripheral delivery of interferon-beta (IFN-beta) for the treatment of
      central nervous system (CNS) diseases is only partially effective because of the
      blood-brain barrier (BBB). To circumvent this problem, we evaluated the
      feasibility of genetically altering bone marrow cells ex vivo and using them as
      vehicles to transfer the IFN-beta cDNA into the mouse CNS. An IFN-beta retroviral
      expression vector (pLXSN-IFNbeta) was used to stably transfect PA317 cells. The
      supernatant from these producer cells, which expressed IFN-beta mRNA and protein,
      were used to infect bone marrow cells. When transplanted into irradiated mice,
      IFN-beta-engineered marrow cells accessed the CNS and expressed IFN-beta mRNA and
      protein. Marrow cells transduced with a control neomycin vector entered the brain
      and expressed the neomycin but not the IFN-beta gene. In the CNS, IFN-beta
      delivered by marrow cells induced the mRNA expression of 2',5'-oligoadenylate
      synthetase (2',5'-OAS), indicating biologic activity. Our findings demonstrating
      that bone marrow cells can serve as a delivery system for IFN-beta cDNA into the
      CNS could have implications for the treatment of neurologic disorders, such as
      multiple sclerosis (MS), viral encephalitis, and brain tumors.

PMID- 12184918
TI  - B cells express Ly-6C in a Th1 but not Th2 cytokine environment.
AB  - Interferon-alpha (IFN-alpha) is the primary regulator of transient Ly-6C
      expression on T cells. B cells, which do not express Ly-6C in the resting state,
      have been reported to express Ly-6C following exposure to proinflammatory
      stimuli. This study examined the factors controlling Ly-6C expression on B cells
      and the kinetics of Ly-6C expression in the presence of these factors. In vivo
      studies demonstrated that proinflammatory (Th1) cytokines transiently upregulate
      B cell Ly-6C expression. In vitro studies identified Th1 cytokines, particularly
      IFN-alpha and IFN-gamma, as the principal cytokines responsible for this
      induction. Polyclonal B cell activators (anti-IgM and recombinant CD40 ligand
      trimer) showed minimal ability to independently induce Ly-6C expression on B
      cells but did enhance the ability of IFNs to induce expression. Th2 cytokine
      environments did not result in B cell Ly-6C expression, and interleukin-4 (IL-4)
      actually antagonized the IFN-driven induction of Ly-6C. Ly6.1 strains of mice
      consistently demonstrated a greater ability to express Ly-6C on B cells than did
      Ly-6.2 strains. Together, these studies demonstrate the ability of Th1 but not
      Th2 cytokine environments to transiently induce the expression of Ly-6C on B
      cells and provide additional evidence for differences in the regulation of Ly-6C
      expression in Ly6.1 and Ly6.2 strains.

PMID- 12184917
TI  - A new assay system for guinea pig interferon biological activity.
AB  - We have developed an assay system for guinea pig interferon (IFN) based on
      reduction of viral cytopathic effect (CPE) in various cell lines. CPE inhibition
      was detected optimally in the guinea pig fibroblast cell line 104C1 infected with
      encephalomyocarditis virus (EMCV). The amount of biologically active guinea pig
      IFN was quantified by estimating viable cell numbers colorimetrically by means of
      a tetrazolium compound, 2-(4-iodophenyl)-3-(4-nitrophenyl)-5-(2,4-disulfophenyl)
      2H-tetrazolium monosodium salt (WST-1) and 1-methoxy-5-methylphenazinium
      methylsulfate (PMS). WST-1 color developed until stopped by the addition of
      sulfuric acid. This had no effect on the colorimetric assay, and the color was
      stable for at least 24 h. The acid also inactivated the EMCV and, thus,
      eliminated the viral hazard. Inhibition of CPE activity was highly correlated
      with the concentration of culture supernatants from BCG-vaccinated guinea pig
      splenocytes stimulated in vitro with tuberculin or an immunostimulatory oligoDNA.
      This assay detected guinea pig IFN and human IFN-alpha, but not IFN-gamma from
      human, mouse, rat, pig, or dog. This assay system has proved useful for the
      titration of guinea pig IFN, being easy to perform, free from viral hazard,
      relatively species specific, highly reproducible, and inexpensive.

PMID- 12184919
TI  - Mycobacterial ESAT-6 protein enhances mouse IFN-gamma responses to Mycoplasma
      hyopneumoniae P71 protein.
AB  - Type 1 immune responses play an important role in the resolution of diseases with
      infectious or oncogenic etiologies. Vaccines for production animals frequently
      target humoral immune responses and are often ineffective in protecting against
      disease. In order to shift the immune response more toward cellular immunity
      (i.e., type 1 response), we tested the ability of a mycobacterial protein, early
      secretory antigenic target (ESAT-6), to enhance interferon-gamma (IFN-gamma)
      secretion during the recall response with a second antigen. The Mycoplasma
      hyopneumoniae membrane protein P71 was used as a test antigen in murine
      vaccination studies. The ESAT-6 open reading frame (ORF) was fused to DNA
      encoding P71 to produce a recombinant protein that was used to immunize BALB/c
      mice. Control mice immunized with P71 alone demonstrated a splenic response
      characterized by release of interleukin-10 (IL-10) and a balanced antigen
      specific IgG1/IgG2a antibody response. The presence of ESAT-6 as a fusion partner
      with P71 during immunization, however, resulted in an enhanced P71-specific IFN
      gamma response, decreased release of IL-10, and significantly greater (p < 0.05)
      IgG2a antibody levels in comparison to immunizing with P71 alone. These results
      demonstrate that ESAT-6 can modify the profile of an immunologic response to an
      accompanying immunogen.

PMID- 12184920
TI  - Immunohistochemical expression analysis of the human interferon-inducible gene
      IFI16, a member of the HIN200 family, not restricted to hematopoietic cells.
AB  - This is the first description of an extensive immunohistochemical analysis of
      interferon (IFN)-inducible gene IFI16 expression in normal tissues.
      Immunohistochemical detection of IFI16 in paraffin-embedded tissues is achieved
      by using a polyclonal antibody raised against its C-terminal fragment that
      recognizes its three closely migrating isoforms in Western blotting. The results
      clearly indicate that IFI16 expression is not restricted to the hematopoietic
      compartment. In normal adult human tissues, it is prominent in stratified
      squamous epithelia and particularly intense in parabasal cells in the
      proliferating compartments, but it gradually decreases in the more differentiated
      suprabasal layers. Understanding of IFI16 expression in vivo is essential for
      interpretation of the results obtained from in vitro studies and elucidation of
      its physiologic role. The constitutive expression and wider distribution of IFI16
      in normal human tissues, not restricted to the hematopoietic compartment,
      strongly support the possibility of an important role in cell differentiation
      that can be further modulated by other stimuli, such as IFN.

PMID- 12184950
TI  - Abstracts of the 7th Conference of the International Endotoxin Society.
      Washington, DC, USA. 18-21 July 2002.

PMID- 12184921
TI  - Pre-pro-B cell growth-stimulating factor (PPBSF) upregulates IL-7Ralpha chain
      expression and enables pro-B cells to respond to monomeric IL-7.
AB  - Although pro-B cells are well represented in IL-7 knockout (KO) mice, they
      express abnormally low concentrations of the interleukin-7 receptor alpha-chain
      (IL-7Ralpha) and do not generate pre-B cells. Here, we demonstrate that pro-B
      cells from IL-7 KO mice can be induced to generate pre-B cells and immature B
      cells by exposure to recombinant IL-7 (rIL-7) in vivo but not in vitro.
      Experiments in recombinant activation gene-1 (RAG-1) KO mice indicate that the in
      vitro unresponsiveness of IL-7(-/-) pro-B cells to rIL-7 is unrelated to the
      absence of a functional pre-B cell receptor (pre-BCR). Rather, it appears to be
      due to the suboptimal expression of the IL-7Ralpha chain. Thus, IL-7(-/-) pro-B
      cells readily respond to rIL-7 in vitro if IL-7Ralpha chain expression is first
      upregulated by exposure to IL-7 in vivo or to IL-7(+/+) bone marrow (BM) stromal
      cells or conditioned medium (CM) therefrom in vitro. Similar results were
      obtained when pro-B cells from IL-7 KO mice were cultured on IL-7(-/-) BM stromal
      cells in the presence of rIL-7. This suggested that the recently described pre
      pro-B cell growth-stimulating factor (PPBSF), a self-assembling hybrid cytokine
      comprising IL-7 and the stromal cell-derived hepatocyte growth factor beta-chain
      (HGFbeta), is required to stimulate pro-B cells from IL-7 KO mice. This inference
      was verified by demonstrating that purified PPBSF upregulates IL-7Ralpha chain
      expression on IL-7(-/-) pro-B cells in vitro and enables them to respond to rIL-7
      in a stepwise manner. We, therefore, postulate that PPBSF is the operative form
      of IL-7 that normally induces IL-7Ralpha(lo) pre-pro-B cells to proliferate and
      differentiate into IL-7Ralpha(hi) pro-B cells, which then proliferate and
      differentiate into pre-B cells on stimulation with monomeric IL-7.

PMID- 12184961
TI  - Clinical inquiries. Should we treat elevated cholesterol in elderly patients?

PMID- 12184962
TI  - Clinical inquiries. What are the treatment options for SSRI-related sexual
      dysfunction?

PMID- 12184963
TI  - Clinical inquiries. What is the best therapy for constipation in infants?

PMID- 12184965
TI  - Dementia: predictors of diagnostic accuracy and the contribution of diagnostic
      recommendations.
AB  - OBJECTIVES: To explore and quantify the relative contribution of guideline
      recommendations and other determinants in the family physicianamprsquos
      diagnostic work-up of patients suspected of dementia. STUDY DESIGN: We
      prospectively studied 64 family physicians in an Eastern district in the
      Netherlands who diagnosed dementia according to the national Dutch guidelines in
      primary care. Their diagnoses were compared with the reference standard embodied
      by the memory clinic team of the University Medical Center Nijmegen. POPULATION:
      The physicians evaluated 107 patients older than 55 years suspected of having
      dementia. OUTCOMES MEASURED: Predictive values of various clinical and
      demographic parameters were measured in both univariate and multivariate logistic
      regression analyses. RESULTS: Activities of daily living (ADL) dependency (odds
      ratio [OR] = 5.3, P =.03), years since symptoms first started (OR = 1.84, P
      =.03), and the presence of somatic comorbidity (OR = 0.48, P =.02) independently
      contributed to the prediction of the presence or absence of dementia. The area
      under the receiver-operating characteristic (ROC) curve for these 3 variables
      together was 0.79. The ROC area of the family physiciansamprsquo diagnosis to
      determine the final diagnosis was 0.74. The number of recommendations applied did
      not additionally contribute to the assessment of the final diagnosis.
      CONCLUSIONS: The diagnostic accuracy of the family physician was reasonable. For
      family physicians, ADL dependency is a better predictor of dementia than
      cognitive impairment. Family physicians should be aware of diagnostic
      difficulties in patients with somatic comorbidity. We were unable to confirm the
      diagnostic value of many of the recommendations of dementia guidelines.

PMID- 12184964
TI  - The third person in the room: frequency, role, and influence of companions during
      primary care medical encounters.
AB  - OBJECTIVE: We wanted to characterize patient accompaniment to medical encounters
      and to explore the rationale and influence of the companion on the primary care
      medical encounter. STUDY DESIGN: This was a descriptive study. POPULATION:
      Academic general internal medicine physicians, patients, and patient companions
      participated. OUTCOMES MEASURED: We measured the frequency of waiting and
      examination room companions, the reasons for accompaniment, the influence on the
      encounter, and the overall helpfulness of the companion as assessed by patients
      and companions. We also determined the physicianamprsquos assessment of the
      companionamprsquos influence, helpfulness, and behavior during the encounter.
      RESULTS: Companions were in the examination room for 16% of visits; 93% were
      family members. The rationales for waiting and examination room companions were
      to help with transportation, provide emotional support, and provide company.
      Examination room companions helped communicate concerns to the physician,
      remember the physicianamprsquos advice, make decisions, and communicate their own
      concerns to the physician. Patients believed that examination room companions
      influenced 75% of medical encounters, mainly by improving communication between
      physician and patient. Physicians agreed that examination room companions
      favorably influenced physician and patient understanding (60% and 46% of
      encounters, respectively). Patients indicated that waiting and examination room
      companions were very helpful for 71% and 83% of visits, respectively.
      CONCLUSIONS: Companions frequently accompany patients to their primary care
      medical encounters. They are often family members, and they assume important
      roles in enhancing patient and physician understanding.

PMID- 12184966
TI  - Aspirin prophylaxis in patients at low risk for cardiovascular disease: a
      systematic review of all-cause mortality.
AB  - OBJECTIVE: We investigated whether aspirin reduces all-cause mortality in low
      risk patients. STUDY DESIGN: We systematically reviewed studies of aspirin for
      primary prevention to measure total mortality. We included all clinical trials,
      cohort studies, and case control studies that assessed primary prevention,
      included low-risk subjects, and measured total mortality. The quality of studies
      was evaluated with a standard scale. DATA SOURCES: MEDLINE, the Cochrane Library,
      and the Internet were systematically searched for studies with the key terms
      primary, prevention, aspirin, myocardial infarction, stroke, and mortality.
      Reference lists of identified trials and reviews also were examined. POPULATION:
      Active members in the Indiana Academy of Family Physicians 2000-2001 membership
      database (N = 1328). OUTCOMES MEASURED: Primary outcomes were myocardial
      infarction, stroke, and mortality. RESULTS: Three primary prevention studies met
      our criteria. Two clinical trials, the United States Physicians Health Study and
      British Doctors Study, demonstrated no significant decrease in mortality in the
      aspirin group alone or when results from the 2 studies were combined. The United
      States Physicians Health Study showed a lower rate of myocardial infarction (odds
      ratio [OR], 0.58; 95% confidence interval [CI], 0.47-0.71). In the Nurses Health
      Study, a cohort study, taking aspirin at any dose was associated with higher
      rates of myocardial infarction (OR, 2.34; CI, 1.92-2.86), stroke (OR, 1.84; CI,
      1.39-2.44), and all-cause mortality (OR, 1.83; CI, 1.57-2.14). CONCLUSIONS: There
      is currently no evidence to recommend for or against the use of aspirin to
      decrease mortality in low-risk individuals.

PMID- 12184969
TI  - Evidence-based guidelines for management of nursing home-acquired pneumonia.
AB  - We convened a multidisciplinary, multispecialty panel to develop comprehensive
      evidence and consensus-based guidelines for managing nursing home-acquired
      pneumonia. The panel began with explicit criteria for process of care quality
      measures, performed a comprehensive review of the English-language literature,
      evaluated the quality of the evidence, and drafted a set of proposed guidelines.
      The panel reviewed the draft, an annotated bibliography, and data from a study of
      30-day survival from nursing home-acquired pneumonia, and then participated in an
      all-day meeting in January 2001. Using a modified Delphi process, the panel
      refined the guidelines and developed a care pathway. The guidelines recommend a
      comprehensive approach, including immunization of staff and residents, and
      communication between nursing staff and the attending physician within 2 hours of
      symptom onset. Probable pneumonia was defined. An algorithm was delineated for
      assessing the patientamprsquos wishes for hospitalization and aggressive care,
      and deciding on hospitalization based on the severity of the illness as well as
      the capacity of the nursing home to provide acute care. The timing and extent of
      evaluation in a nursing home relative to the rapid initiation of antibiotics
      should depend on whether the patient has any unstable vital signs. An antibiotic
      covering Streptococcus pneumoniae, Haemophilus influenzae, common gram-negative
      rods, and Staphylococcus aureus should be given for 10 to 14 days, orally if the
      patient is able to take medications by mouth.

PMID- 12184970
TI  - Symptoms don't predict response to antibiotics.

PMID- 12184971
TI  - Effects of soil temperature on parameters of a coupled photosynthesis-stomatal
      conductance model.
AB  - To examine the effects of soil temperature on a coupled photosynthesis-stomatal
      conductance model, seedlings of trembling aspen (Populus tremuloides Michx.),
      jack pine (Pinus banksiana Lamb.), black spruce (Picea Mariana (Mill.) B.S.P.)
      and white spruce (Picea glauca (Moench) Voss) were exposed to soil temperatures
      ranging from 5 to 35 degrees C for 4 months. Light and CO(2) response curves of
      foliar gas exchange were measured for model parameterization. The effects of soil
      temperature on four key model parameters, V(cmax) (maximum rate of
      carboxylation), J(max) (maximum rate of electron transport), alpha (energy
      conversion efficiency or quantum efficiency of electron transport) and R(d)
      (daytime dark respiration), were modeled using two third-order polynomial
      equations and a modified Arrhenius equation. In all species, V(cmax) and J(max)
      increased with soil temperature up to an optimum, and then decreased with further
      increases in soil temperature. In the conifers, alpha showed a similar response
      to soil temperature as V(cmax) and J(max), but soil temperature had no
      significant effect on alpha in aspen. Soil temperature had no significant effect
      on R(d) in any species. The three equations described the relationships between
      soil temperature and the model parameters reasonably well, but performed best for
      V(cmax) and worst for alpha. No significant relationships were identified between
      soil temperature and the parameters of the stomatal conductance model.

PMID- 12184972
TI  - Enhanced tolerance of photosynthesis to high-light and drought stress in
      Pseudotsuga menziesii seedlings grown in ultraviolet-B radiation.
AB  - We investigated the effects of an ambient dose of ultraviolet-B (UV-B) radiation
      on chamber-grown Pseudotsuga menziesii var. glauca (Beissn.) Franco (Douglas-fir)
      seedlings, to determine if the presence of UV-B radiation in the growth light
      regime induces tolerance to environmental stresses such as high light and
      drought. Douglas-fir seedlings were grown without UV-B radiation or with 6 kJ m-2
      day-1 of biologically effective UV-B, which is ambient for the intermountain
      regions of Idaho. Non-stressed seedlings grown with UV-B radiation had 35% lower
      seedling dry mass, 36% higher concentrations of UV-B absorbing compounds per unit
      leaf area, 30% lower stomatal frequencies, 25% lower light-saturated
      photochemical efficiencies of Photosystem II and 45% lower light-saturated
      stomatal conductance than non-stressed seedlings grown without UV-B radiation.
      After 4 days of high-light stress, seedlings grown with UV-B radiation had 32%
      higher light-saturated carbon assimilation rates (A(CO2)) than seedlings grown
      without UV-B radiation. After water was withheld from the seedlings for up to 15
      days, seedlings grown with UV-B radiation had 50% higher A(CO2) and 40% higher
      seedling water potentials than seedlings grown without UV-B radiation. The
      results support the hypothesis that UV-B radiation can act as an environmental
      signal to induce tolerance to high-light and drought stress in Douglas-fir
      seedlings. Possible mechanisms for the enhanced stress tolerance are discussed.

PMID- 12184973
TI  - Impacts of seasonal air and soil temperatures on photosynthesis in Scots pine
      trees.
AB  - Seasonal courses of light-saturated rate of net photosynthesis (A360) and
      stomatal conductance (gs) were examined in detached 1-year-old needles of Scots
      pine (Pinus sylvestris L.) from early April to mid-November. To evaluate the
      effects of soil frost and low soil temperatures on gas exchange, the extent and
      duration of soil frost, as well as the onset of soil warming, were manipulated in
      the field. During spring, early summer and autumn, the patterns of A360 and gs in
      needles from the control and warm-soil plots were generally strongly related to
      daily mean air temperatures and the frequency of severe frost. The warm-soil
      treatment had little effect on gas exchange, although mean soil temperature in
      the warm-soil plot was 3.8 degrees C higher than in the control plot during
      spring and summer, indicating that A360 and gs in needles from control trees were
      not limited by low soil temperature alone. In contrast, prolonged exposure to
      soil temperatures slightly above 0 degrees C severely restricted recovery of A360
      and especially gs in needles from the cold-soil treatment during spring and early
      summer; however, full recovery of both A360 and gs occurred in late summer. We
      conclude that inhibition of A360 by low soil temperatures is related to both
      stomatal closure and effects on the biochemistry of photosynthesis, the relative
      importance of which appeared to vary during spring and early summer. During the
      autumn, soil temperatures as low as 8 degrees C did not affect either A360 or gs.

PMID- 12184974
TI  - Physiological traits of two Populus x euramericana clones, Luisa Avanzo and
      Dorskamp, during a water stress and re-watering cycle.
AB  - We compared responses to drought and re-watering of greenhouse-grown cuttings of
      Populus x euramericana (Dode) Guinier clones, Luisa Avanzo and Dorskamp. Total
      leaf area, leaf number, leaf area increment and stomatal conductance were
      evaluated periodically during a 29-day drought period and for 16 days after re
      watering. Soil water content and predawn leaf water potential (Psi(wp)) were
      measured on Days 29 and 45. On the same days, relative water content (RWC),
      specific leaf area (SLA), nitrogen, chlorophyll, soluble sugars, total phenols,
      flavanols and antioxidant activity were determined for leaves taken from the
      bottom to the top of each cutting. Leaves of Luisa Avanzo cuttings grew more
      rapidly than leaves of Dorskamp and exhibited higher SLA, but lower
      concentrations of nitrogen, chlorophyll and soluble sugars and lower antioxidant
      activity per unit area. On Day 29, after withholding water, both clones had
      closed their stomata, reduced rates of leaf growth, and lower Psi(wp) and RWC;
      however, the clones differed in their responses to soil water depletion. Compared
      to Dorskamp, Luisa Avanzo closed its stomata earlier and maintained higher
      Psi(wp), but lower RWC and leaf sugar concentrations. Antioxidant activity of
      leaf methanolic extracts decreased in response to water stress only in Luisa
      Avanzo. Leaf physiology and its modulation by water stress were age dependent in
      Luisa Avanzo.

PMID- 12184975
TI  - Energy investment in leaves of red maple and co-occurring oaks within a forested
      watershed.
AB  - Despite its recent expansion in eastern US forests, red maple (Acer rubrum L.)
      generally exhibits a low leaf photosynthetic rate, leaf mass per unit area (LMA)
      and leaf nitrogen concentration ([N]) relative to co-occurring oaks (Quercus
      spp.). To evaluate these differences from the perspective of leaf energy
      investment, we compared leaf construction cost (CC) and leaf maintenance cost
      (MC) with leaf photosynthetic rate at saturating photon flux density and ambient
      CO2 partial pressure (Amax) in red maple and co-occurring red oak (Quercus rubra
      L.) and chestnut oak (Quercus prinus L.). We also examined relationships among
      leaf physiological, biochemical and structural characteristics of upper-canopy
      leaves of these three species at lower (wetter) and upper (drier) elevation sites
      of a watershed in the Black Rock Forest, Cornwall, NY, USA. Although A(max), leaf
      [N], leaf carbon concentration ([C]) and LMA were significantly less in red maple
      than in either oak species at both sites, CC per unit leaf area of red maple was
      28.2 and 35.4% less than that of red oak at the lower and upper site,
      respectively, and 38.8 and 32% less than that of chestnut oak at the lower and
      upper site, respectively. Leaf MC per unit leaf area, which was positively
      associated with leaf CC (r2 = 0.95), was also significantly lower in red maple
      than in either oak species at both sites. When expressed per unit leaf area,
      A(max) was positively correlated with both CC (r2 = 0.65) and MC (r2 = 0.59). The
      cost/benefit ratio of CC/Amax of red maple was significantly less than that of
      chestnut oak at the lower site, however, CC/A(max) did not exhibit any
      significant interspecific differences at the upper site. Expressed per unit leaf
      area, CC was correlated positively with LMA (r2 = 0.90), leaf [N] (r2 = 0.97),
      and leaf [C] (r2 = 0.89), and negatively correlated with leaf molar carbon to
      nitrogen ratio (r2 = 0.92). Combined with red maple's general success in many oak
      dominated forests, our findings suggest that reduced leaf-level photosynthetic
      capacity and related leaf characteristics in red maple are partially balanced by
      lower energy and resource requirements for leaf biomass construction and
      maintenance, which could enhance the competitive success of this species.

PMID- 12184976
TI  - Biochemical responses to iron deficiency in kiwifruit (Actinidia deliciosa).
AB  - A comparative study of two kiwifruit genotypes (Actinidia deliciosa (A. Chev.)
      C.F. Liang et A.R. Ferguson var. deliciosa) with different tolerance to iron (Fe)
      deficiency was conducted to identify biochemical features associated with
      tolerance to Fe deficiency. After 14 days of growth in hydroponic culture under
      Fe-deficient and Fe-sufficient conditions, leaf chlorophyll concentration,
      activities of ferric chelate reductase (FCR), phosphoenolpyruvate carboxylase
      (PEPC) and citrate synthase in root extracts, concentrations of organic acids in
      roots, leaves and xylem sap, and xylem sap pH were measured. In response to Fe
      deficiency, the tolerant genotype D1 showed: (i) higher FCR activity associated
      with a longer lasting induction of FCR; (ii) higher PEPC activity; (iii) higher
      concentrations of citric acid in roots; and (iv) lower xylem sap pH compared with
      the susceptible genotype Hayward. These findings imply that induction of FCR and
      PEPC activities in roots in response to Fe deficiency are important physiological
      adaptations enabling Fe-efficient kiwifruit plants to tolerate Fe deficiency.

PMID- 12184978
TI  - Influence of shoot architectural position on shoot growth and branching patterns
      in Cleyera japonica.
AB  - The influence of shoot architectural position on shoot growth and branching
      patterns was examined in saplings of Cleyera japonica Thunb. (Theaceae), an
      understory, broad-leaf evergreen woody species. Shoot length varied with
      branching order and the vertical position of the branch in the crown. In the
      upper crown, shoot length decreased with increasing branching order, whereas in
      the lower crown, differences in shoot length among branching orders were not
      significant. These results demonstrate that it is important to consider not only
      individual shoots, but also the relationships between shoots in terms of their
      architectural positions when studying the development of crown architecture in
      trees. Shoot branching patterns also varied with branching order and the vertical
      position of the branch in the crown. In the upper crown, branching was mainly
      sylleptic. In the middle of the crown, mainly proleptic branches were produced.
      In the lower crown, there was little branching. The importance of these trends in
      shoot growth and shoot branching patterns in terms of carbon production
      efficiency is discussed.

PMID- 12184977
TI  - Canopy stomatal conductance and xylem sap abscisic acid (ABA) in mature Scots
      pine during a gradually imposed drought.
AB  - We investigated the effect of drought on canopy stomatal conductance (g(c)), and
      examined the hypothesis that g(c) is controlled by the chemical messenger
      abscisic acid (ABA) produced in roots. Beginning in November 1994, we subjected a
      mature stand of Scots pine (Pinus sylvestris L.) to an imposed 11-month drought.
      Control plots were maintained at average-season soil water content. Xylem sap was
      extracted from shoots at regular intervals from April to November 1995. Soil
      water, sap flow and leaf water potentials (predawn to dusk) were recorded at the
      same time. Canopy stomatal conductance was calculated from sap flow data and
      xylem sap ABA concentrations ([ABA(xyl)]) were measured by radioimmunoassay. Mean
      [ABA(xyl)] in control trees was 250 micromol m(-3). No diurnal variation in
      [ABA(xyl)] was detected. With soil drying, [ABA(xyl)] increased to a maximum in
      summer (600 micromol m(-3)), but decreased again toward autumn; however, no
      significant increase in ABA flux to the leaves occurred. A decline in g(c) was
      detected when volumetric soil water content declined below 0.12. The decline in
      g(c) could not have been mediated by increasing [ABA(xyl)] because stomatal
      closure appeared to precede any increase in [ABA(xyl)]. Peak sap flow velocity
      data were used to estimate delivery times for root-to-shoot signals in 15-m tall
      trees. Under normal field conditions, a signal would take 12 days to travel from
      the site of production (roots) to the presumed site of action (shoots). However,
      under drought conditions it may take a chemical signal in excess of 6 weeks. We
      conclude that a feedforward model of short-term stomatal response to soil drying,
      based solely on the action of a chemical messenger from the roots, is not
      applicable in mature conifer trees because signal transmission is too slow.

PMID- 12184979
TI  - Dependence of needle architecture and chemical composition on canopy light
      availability in three North American Pinus species with contrasting needle
      length.
AB  - Morphology and chemical composition of needles of shade-intolerant southern
      conifers (Pinus palustris Mill. (mean needle length +/- SD = 29.1 +/- 4.1 cm), P.
      taeda L. (12.3 +/- 2.9 cm) and P. virginiana Mill. (5.1 +/- 0.8 cm)) were studied
      to test the hypothesis that foliage acclimation potential to canopy light
      gradients is generally low for shade-intolerant species, and in particular,
      because of mechanical limitations, in species with longer needles. Plasticity for
      each needle variable was defined as the slope of the foliar characteristic versus
      irradiance relationship. A novel geometrical model for needle area and volume
      calculation was employed for the three-needled species P. palustris and P. taeda.
      Needle thickness (T) strongly increased, but width (W) was less variable with
      increasing daily integrated quantum flux density averaged over the season
      (Q(int)), resulting in changes in cross-sectional needle shape that were
      manifested in a positive relationship between the total to projected needle area
      ratio (A(T)/A(P)) and Q(int) in the three-needled species. In contrast, cross
      sectional needle geometry was only slightly modified by irradiance in the two
      needled conifer P. virginiana. Needle dry mass per unit total needle area (M(T))
      was positively related to Q(int) in all species, leading to greater foliar
      nitrogen contents per unit area at higher irradiances. Separate examination of
      the components of M(T) (density (D) and the volume (V) to A(T) ratio; M(T) =
      DV/A(T)) indicated that the positive effect of light on M(T) resulted solely from
      increases in V/A(T), i.e., from increases in the thickness of foliage elements.
      Foliar chlorophyll content per unit mass increased with increasing Q(int),
      allowing an improvement in light-harvesting efficiency in low light. The
      variables characterizing needle material properties (D, the dry to fresh mass
      ratio, and needle carbon content per unit mass) were generally independent of
      Q(int), suggesting that needles were less stiff and had greater tip deflections
      under their own weight at lower irradiances because of smaller W and T.
      Comparisons with the literature revealed that plasticity in foliar
      characteristics tended to be lower in the studied shade- intolerant species than
      in shade-tolerant conifers, but plasticity among the investigated species was
      unaffected by needle length. However, we argue that, because of mechanical
      limitations, plastic changes in needle cross section in response to low
      irradiance may decrease rather than increase light-interception efficiency in
      long-needled species.

PMID- 12184980
TI  - An investigation of hydraulic limitation and compensation in large, old Douglas
      fir trees.
AB  - The hydraulic limitation hypothesis (Ryan and Yoder 1997) proposes that leaf
      specific hydraulic conductance (kl) and stomatal conductance (gs) decline as
      trees grow taller, resulting in decreased carbon assimilation. We tested the
      hydraulic limitation hypothesis by comparison of canopy-dominant Douglas-fir
      (Pseudotsuga menziesii var. menziesii (Mirb.) Franco) trees in stands that were
      approximately 15 m (20 years old), 32 m (40 years old) and 60 m (> 450 years old)
      tall in Wind River, Washington, USA. Carbon isotope discrimination (Delta)
      declined with tree height (18.6, 17.6 and 15.9 per thousand for stands 15, 32 and
      60 m tall, respectively) indicating that gs may have declined proportionally with
      tree height in the spring months, when carbon used in the construction of new
      foliage is assimilated. Hydraulic conductance decreased by 44% as tree height
      increased from 15 to > 32 m, and showed a further decline of 6% with increasing
      height. The general nonlinear pattern of kl versus height was predicted by a
      model based on Darcy's Law. Stemwood growth efficiency also declined nonlinearly
      with height (60, 35 and 28 g C m-2 leaf area for the 15-, 32- and 60-m stands,
      respectively). Unlike kl and growth efficiency, gs and photosynthesis (A) during
      summer drought did not decrease with height. The lack of decline in cuvette-based
      A indicates that reduced A, at least during summer months, is not responsible for
      the decline in growth efficiency. The difference between the trend in gs and A
      and that in kl and D may indicate temporal changes (spring versus summer) in the
      response of gas exchange to height-related changes in kl or it may be a result of
      measurement inadequacies. The formal hydraulic limitation hypothesis was not
      supported by our mid-summer gs and A data. Future tests of the hydraulic
      limitation hypothesis in this forest should be conducted in the spring months,
      when carbon uptake is greatest. We used a model based on Darcy's Law to quantify
      the extent to which compensating mechanisms buffer hydraulic limitations to gas
      exchange. Sensitivity analyses indicated that without the observed increases in
      the soil-to-leaf water potential differential (DeltaPsi) and decreases in the
      leaf area/sapwood area ratio, kl would have been reduced by more than 70% in the
      60-m trees compared with the 15-m trees, instead of the observed decrease of 44%.
      However, compensation may have a cost; for example, the greater DeltaPsi of the
      largest trees was associated with smaller tracheid diameters and increased
      sapwood cavitation, which may have a negative feedback on kl and gs.

PMID- 12184981
TI  - Measured and predicted changes in tree and stand water use following high
      intensity thinning of an 8-year-old Eucalyptus nitens plantation.
AB  - We investigated changes in the pattern of water use of an 8-year-old Eucalyptus
      nitens (Deane and Maiden) Maiden plantation soon after thinning. Sap flow sensors
      using heat pulse technology were deployed across three stands thinned to a final
      density of 100, 250 or 600 trees ha-1 plus an unthinned control (1250 trees ha
      1). Changes in the relationship between tree size and daily water use were
      measured for 4 to 7 months after thinning. Thinning had no effect on sapwood
      water content. The increase in tree water use as a result of thinning was driven
      largely by significant changes in the radial pattern of sap velocity through the
      sapwood. The use of a canopy fraction factor in the Penman-Monteith equation to
      account for discontinuous canopies showed promise as a simple and effective
      method of scaling the model to predict transpiration from thinned plantations.

PMID- 12184982
TI  - Role of organic acids in aluminum accumulation and plant growth in Melastoma
      malabathricum.
AB  - Melastoma malabathricum L. (melastoma) is an Al-accumulating woody plant that
      grows in tropical Southeast Asia in acid soils with high aluminum (Al)
      concentrations and low nutrient concentrations. Because oxalate serves as a
      ligand for Al accumulation in melastoma leaves and citrate is the ligand
      associated with Al translocation from roots to shoots, we investigated the role
      of organic acids in the adaptation of melastoma to growth on these soils.
      Phosphorus starvation increased oxalate concentration in the rhizosphere,
      enabling melastoma to solubilize insoluble aluminum phosphate in the rhizosphere.
      Increased availability of P and Al in the rhizosphere enhanced growth. In the
      xylem sap, the concentration of citrate increased with increasing Al
      concentration. In contrast, the concentrations of malate, succinate and alpha
      ketoglutarate in the xylem sap decreased with increasing Al concentration,
      suggesting that tricarboxylic acid cycle enzymes were affected by Al treatment.

PMID- 12184983
TI  - Winter water relations of New England conifers and factors influencing their
      upper elevational limits. I. Measurements.
AB  - The upper elevational limits of tree species are thought to be controlled by
      abiotic factors such as temperature and the soil and atmospheric conditions
      affecting plant water status. We measured relative water contents (RWC), water
      potentials (Psi) and cuticular conductances (g(c)) of shoots of four conifer
      species-eastern hemlock (Tsuga canadensis (L.) Carr.), eastern white pine (Pinus
      strobus L.), red pine (P. resinosa Ait.) and red spruce (Picea rubens Sarg.)
      during two winters on Mt. Ascutney, Vermont, USA. Some micrometeorological
      measurements are also reported. Eastern hemlock and white pine were studied near
      their upper elevational limits at a 640-m site, and red pine was studied near its
      upper elevational limit at 715 m. Red spruce was also studied at the 715-m site,
      which is in the middle of its elevational range on this mountain. There was no
      evidence of winter desiccation stress in any species. The observed distribution
      of seedlings suggested that the upper elevational limits on shade-intolerant
      eastern white pine and red pine are set by the absence of suitable seed beds
      after 100 years without fire. Eastern hemlock is able to reproduce in deep shade
      on organic substrates, but germination at high elevations may be restricted by
      low temperatures.

PMID- 12184984
TI  - Winter water relations of New England conifers and factors influencing their
      upper elevational limits. II. Modeling.
AB  - We used the water relations model, WINWAT, to model winter water relations of
      three conifer species-eastern hemlock (Tsuga canadensis (L.) Carr.), eastern
      white pine (Pinus strobus L.) and red pine (P. resinosa Ait.)-growing at their
      upper elevational limits on Mt. Ascutney, Vermont, USA, in the winters of 1997
      and 1999. Modeled relative water contents remained above 60% in the two youngest
      foliar age classes of all three species during both winters, indicating that
      desiccation stress in winter is not responsible for setting the upper elevational
      limits of these species at this site under present climatic conditions. WINWAT
      indicated that winter water relations of these low-elevational species were
      sensitive to low relative humidity, which increased transpiration rates, and low
      temperatures, which inhibited recharge, but are much less sensitive to summer
      climate than in the case of subalpine conifers in Colorado. Our results indicate
      that summer and winter temperatures and relative humidities (or
      precipitation/potential evapotranspiration ratios) should be incorporated into
      climate change models designed to simulate future tree distributions.

PMID- 12184985
TI  - Microelectrode technique for in situ measurement of carbon dioxide concentrations
      in xylem sap of trees.
AB  - We developed a new microelectrode technique for measuring CO2 concentration
      ([CO2]) in xylem sap of trees. This technique enabled us to make rapid and
      continuous measurements of xylem sap [CO2] in situ. In this report, we discuss
      the methodology and establish the feasibility of the technique. We also describe
      calibration procedures, temperature sensitivity, field use and other
      characteristics of the microelectrodes. An example of data collected in the field
      is provided. Microelectrode calibration was accomplished at constant temperature
      in air of known [CO2]. When sampling temperature differed from calibration
      temperature, correction was necessary. We developed an equation to correct for
      temperatures between 15 and 35 degrees C when calibration was conducted at 25
      degrees C. Equations based on Henry's Law were used to convert measured gas phase
      [CO2] (%) to concentration of all products of CO2 dissolved in sap (mmol l(-1)).
      We inserted microelectrodes into stems of three tree species to measure diurnal
      changes in [CO2] in the xylem sap. A diurnal pattern with depression during the
      day and elevation at night was observed. Mean daily [CO2] ranged from 1.6 to 10.3
      mmol l(-1). Microelectrodes were suitable for making diurnal measurements for up
      to 7 days without recalibration. We also used the microelectrodes to measure
      [CO2] of soil in situ. Soil [CO2] ranged from 1 to 4% (gas phase), with little
      diurnal variation.

PMID- 12184986
TI  - Genomic DNA methylation-demethylation during aging and reinvigoration of Pinus
      radiata.
AB  - In animals, DNA methylation is related to gene silencing during ontogenic
      development. Little is known about DNA methylation in plants, although occasional
      changes in the DNA methylation state of specific gene promoters have been
      reported in angiosperms during some developmental processes. We found large
      differences in the extent of DNA methylation between meristematic areas of
      juvenile and mature Pinus radiata D. Don. trees, whereas differences in the
      extent of DNA methylation between differentiated tissues of juvenile and mature
      trees were small. In meristematic areas, there was a gradual decrease in extent
      of DNA methylation as the degree of reinvigoration increased. The observed
      changes in extent of DNA methylation during aging and reinvigoration indicate
      that reinvigoration could be a consequence of epigenetic modifications opposite
      in direction to those that occur during aging.

PMID- 12184987
TI  - Adrenomedullin binding protein-1 modulates vascular responsiveness to
      adrenomedullin in late sepsis.
AB  - Adrenomedullin (AM), a potent vasodilatory peptide, plays an important role in
      initiating the hyperdynamic response during the early stage of sepsis. Moreover,
      the reduced vascular responsiveness to AM appears to be responsible for the
      transition from the early, hyperdynamic to the late, hypodynamic phase of sepsis.
      Although the novel specific AM binding protein-1 (AMBP-1) enhances AM-mediated
      action in a cultured cell line, it remains to be determined whether AMBP-1 plays
      any role in modulating vascular responsiveness to AM during sepsis. To study
      this, adult male rats were subjected to sepsis by cecal ligation and puncture
      (CLP). The thoracic aorta was harvested for determination of AM-induced vascular
      relaxation. Aortic levels of AMBP-1 were determined by Western blot analysis, and
      AM receptor gene expression in the aortic tissue was assessed by RT-PCR. The
      results indicate that AMBP-1 significantly enhanced AM-induced vascular
      relaxation in aortic rings from sham-operated animals. Although vascular
      responsiveness to AM decreased at 20 h after CLP (i.e., the late, hypodynamic
      stage of sepsis), addition of AMBP-1 in vitro restored the vascular relaxation
      induced by AM. Moreover, the aortic level of AMBP-1 decreased significantly at 20
      h after CLP. In contrast, AM receptor gene expression was not altered under such
      conditions. These results, taken together, suggest that AMBP-1 plays an important
      role in modulating vascular responsiveness to AM, and the reduced AMBP-1 appears
      to be responsible for the vascular AM hyporesponsiveness observed during the
      hypodynamic phase of sepsis.

PMID- 12184988
TI  - Evidence for microvascular dysfunction after prenatal dexamethasone at 0.7, 0.75,
      and 0.8 gestation in sheep.
AB  - Dexamethasone (DM) was administered to pregnant ewes as three weekly courses of
      four injections of 2 mg at 12-h intervals. DM (n = 7) or saline (n = 7) was given
      starting at 103 days of gestation (dGA; term approximately 149 days). Fetal
      femoral arteries (approximately 300-microm internal diameter) were evaluated
      using wire myography at 119 dGA. DM-exposed fetuses were significantly smaller
      than saline-exposed fetuses. DM exposure increased maximal contraction to 125 mM
      KCl, and maximum tension developed along with sensitivity to endothelin-1 and
      relaxation to bradykinin. Preincubation with the nitric oxide synthase inhibitor
      N(G)-nitro-L-arginine methyl ester shifted the dose-response curves to endothelin
      1 and acetylcholine to the right in controls but not in the DM-exposed group.
      Relaxation to acetylcholine and to the nitric oxide donor sodium nitroprusside
      was similar in both groups. The combination of enhanced endothelin-induced
      vasoconstriction, abnormal endothelium-dependent relaxation, and normal
      endothelium-independent relaxation indicates microvessel dysfunction following
      antenatal DM administration. Because such dysfunction is associated with several
      forms of adult hypertension, our results indicate the potential for consequences
      of antenatal glucocorticoid exposure on adult cardiovascular health.

PMID- 12184989
TI  - Cardiovascular responses to static and dynamic contraction during comparable
      workloads in humans.
AB  - Previous studies suggest that the blood pressure response to static contraction
      is greater than that caused by dynamic exercise. In anesthetized cats, however,
      pressor responses to electrically induced static and dynamic contraction of the
      same muscle group are similar during equivalent workloads and peak tension
      development [i.e., similar tension-time index (TTI)]. To determine if the same
      relationship exists in humans, where contraction is voluntary and central command
      is present, dynamic (180 s; 1/s) and static (90 s) contractions at 30% of maximal
      voluntary contraction (MVC) were performed. Dynamic contraction also was repeated
      at the same TTI for 90 s at 60% MVC. Mean arterial pressure (MAP), heart rate
      (HR), cardiac output (CO), MAP during postexercise arterial occlusion (an index
      of the metaboreceptor-induced activation of the exercise pressor reflex), and
      relative perceived exertion (RPE) (an index of central command) were assessed. No
      differences in these variables were found between static and dynamic contraction
      at a tension of 30% MVC. During dynamic contraction at 60% MVC, changes in MAP
      (16 +/- 3 vs. 19 +/- 4 mmHg) and absolute HR (92 +/- 6 vs. 69 +/- 5 beats/min),
      CO (7.9 +/- 0.4 vs. 6.3 +/- 0.3 l/min), RPE (16 +/- 1 vs. 13 +/- 1), and MAP
      during postexercise arterial occlusion (115 +/- 3 vs. 100 +/- 4 mmHg) were
      greater than during static contraction (P < 0.05). Thus increases in MAP and HR,
      activation of central command, and muscle metabolite-induced stimulation of the
      exercise pressor reflex during static and dynamic contraction in humans seem to
      be similar when peak tension and TTI are equal. Augmented responses to dynamic
      contraction at 60% MVC are likely related to greater activation of these two
      mechanisms.

PMID- 12184990
TI  - NK(1) receptor and its interaction with NMDA receptor in spinal c-fos expression
      after lower urinary tract irritation.
AB  - The role of neurokinin 1 (NK(1)) receptor and possible interaction between NK(1)
      and N-methyl-D-aspartic acid (NMDA) glutamatergic receptors were investigated on
      spinal c-fos expression after lower urinary tract irritation with acetic acid
      infusion in rats. At both levels of the first (L(1)) and sixth lumbar (L(6))
      spinal cord, where most of hypogastric nerve and pelvic nerve afferent terminals
      project, respectively, the selective NK(1) receptor antagonist CP-99,994 dose
      dependently reduced the total number of c-fos protein (Fos)-positive cells.
      However, CP-100,263, the enantiomer of CP-99,994 with a very low affinity for
      NK(1) receptor, did not have any effect on the total number of Fos-positive
      cells. Coadministration of a low dose (1 mg/kg) of CP-99,994 and NMDA receptor
      antagonist (MK-801), either of which alone did not affect c-fos expression,
      significantly inhibited c-fos expression at both levels of the spinal cord.
      Regarding regional differences, the number of Fos-positive cells decreased
      significantly at all regions of the L(6) level, but only at the dorsal horn of
      the L(1) level. These results indicate that NK(1) receptor is involved in spinal
      c-fos expression after lower urinary tract irritation and that NK(1) and NMDA
      receptors have a synergistic interaction in the spinal processing of nociceptive
      input from the lower urinary tract.

PMID- 12184991
TI  - Diaphragm contractile dysfunction in MyoD gene-inactivated mice.
AB  - MyoD is one of four myogenic regulatory factors found exclusively in skeletal
      muscle. In an effort to better understand the role that MyoD plays in determining
      muscle contractile properties, we examined the effects of MyoD deletion on both
      diaphragmatic contractile properties and myosin heavy chain (MHC) phenotype.
      Regions of the costal diaphragm from wild-type and MyoD knockout [MyoD (-/-)]
      adult male BALB/c mice (n = 8/group) were removed, and in vitro diaphragmatic
      contractile properties were measured. Diaphragmatic contractile measurements
      revealed that MyoD (-/-) animals exhibited a significant (P < 0.05) downward
      shift in the force-frequency relationship, a decrement in maximal specific
      tension (P(o); -33%), a decline in maximal shortening velocity (V(max); -37%),
      and concomitant decrease in peak power output (-47%). Determination of MHC
      isoforms in the diaphragm via gel electrophoresis revealed that MyoD elimination
      resulted in a fast-to-slow shift (P < 0.05) in the MHC phenotype toward MHC types
      IIA and IIX in MyoD (-/-) animals. These data indicate that MyoD deletion results
      in a decrease in diaphragmatic submaximal force generation and P(o), along with
      decrements in both V(max) and peak power output. Hence, MyoD plays an important
      role in determining diaphragmatic contractile properties.

PMID- 12184993
TI  - Comparison of the effects of ammonia on brain mitochondrial function in rats and
      gulf toadfish.
AB  - We compared the effect of hyperammonemia on NADH levels in brain slices and on
      the rate of oxygen consumption from isolated nonsynaptic brain mitochondria in
      ammonia-sensitive Wistar rats with that in ammonia-tolerant gulf toadfish
      (Opsanus beta). The NADH content was significantly decreased (12% less than
      control after 45 min with 1 mM NH(4)Cl) in rat brain slices, but it was not
      affected in brain slices from toadfish (with both 1 and 6 mM NH(4)Cl). The rates
      of oxygen consumption of different sets of enzymes of the electron transport
      chain (ETC; complexes I, II, III, and IV; II, III, and IV; and IV alone) were
      unaltered by hyperammonemic conditions in isolated nonsynaptic mitochondria from
      either rats or toadfish. These results lead us to conclude that the differing
      effects of ammonia on NADH levels in rat and toadfish brain slices must be due to
      aspects other than the direct effects of ammonia on enzymes of the ETC.
      Additionally, because these effects were seen in vitro, our studies enabled us to
      rule out the possibility that effects of ammonia on metabolism were via indirect
      systemic effects. These results are discussed in the context of current views on
      mechanisms of central nervous system damage in hyperammonemic states.

PMID- 12184992
TI  - Disinhibition of female sexual behavior by a CRH receptor antagonist in Syrian
      hamsters.
AB  - Several conditions that inhibit female sexual behavior are thought to be
      associated with altered corticotropin-releasing hormone (CRH) activity in the
      brain. The present experiments examined the hypothesis that endogenous CRH
      receptor signaling mediates the inhibition of estrous behavior by undernutrition
      and in other instances of sexual dysfunction. Intracerebroventricular (ICV)
      infusion of CRH or urocortin inhibited estrous behavior in ovariectomized steroid
      primed hamsters. Conversely, ICV infusion of the CRH receptor antagonist
      astressin prevented the suppression of estrous behavior by food deprivation or by
      ICV administration of neuropeptide Y. Astressin treatment also induced sexual
      receptivity in nonresponders, animals that do not normally come into heat when
      treated with hormones, and this effect persisted in subsequent weekly tests in
      the absence of any further astressin treatment. Activation of the hypothalamo
      pituitary-adrenocortical axis was neither necessary nor sufficient to inhibit
      estrous behavior, indicating that this phenomenon is due to other central actions
      of CRH receptor agonists. This is the first direct evidence that CRH receptor
      signaling may be a final common pathway by which undernutrition and other
      conditions inhibit female sexual behavior.

PMID- 12184994
TI  - Increased GABA(A) inhibition of the RVLM after hindlimb unloading in rats.
AB  - Attenuated baroreflex-mediated increases in renal sympathetic nerve activity
      (RSNA) in hindlimb unloaded (HU) rats apparently are due to changes within the
      central nervous system. We hypothesized that GABA(A) receptor-mediated inhibition
      of the rostral ventrolateral medulla (RVLM) is increased after hindlimb
      unloading. Responses to bilateral microinjection of the GABA(A) antagonist (-)
      bicuculline methiodide (BIC) into the RVLM were examined before and during caudal
      ventrolateral medulla (CVLM) inhibition in Inactin-anesthetized control and HU
      rats. Increases in mean arterial pressure (MAP), heart rate (HR), and RSNA in
      response to BIC in the RVLM were significantly enhanced in HU rats. Responses to
      bilateral CVLM blockade were not different. When remaining GABA(A) inhibition in
      the RVLM was blocked by BIC during CVLM inhibition, the additional increases in
      MAP and RSNA were significantly greater in HU rats. These data indicate that
      GABA(A) receptor-mediated inhibition of RVLM neurons is augmented after hindlimb
      unloading. Effects of input from the CVLM were unaltered. Thus, after
      cardiovascular deconditioning in rodents, the attenuated increase in sympathetic
      nerve activity in response to hypotension is associated with greater GABA(A)
      receptor-mediated inhibition of RVLM neurons originating at least in part from
      sources other than the CVLM.

PMID- 12184995
TI  - Endothelin-1 and -3 diminish neuronal NE release through an NO mechanism in rat
      anterior hypothalamus.
AB  - The existence of endothelin binding sites on the catecholaminergic neurons of the
      hypothalamus suggests that endothelins (ETs) participate in the regulation of
      noradrenergic transmission modulating various hypothalamic-controlled processes
      such as blood pressure, cardiovascular activity, etc. The effects of ET-1 and ET
      3 on the neuronal release of norepinephrine (NE) as well as the receptors and
      intracellular pathway involved were studied in the rat anterior hypothalamus. ET
      1 (10 nM) and ET-3 (10 nM) diminished neuronal NE release and the effect blocked
      by the selective ET type B receptor antagonist BQ-788 (100 nM). N(omega)-nitro-L
      arginine methyl ester (10 microM), methylene blue (10 microM), and KT5823 (2
      microM), inhibitors of nitric oxide synthase activity, guanylate cyclase, and
      protein kinase G, respectively, prevented the inhibitory effects of both ETs on
      neuronal NE release. In addition, both ETs increased nitric oxide synthase
      activity. Furthermore, 100 microM picrotoxin, a GABA(A)-receptor antagonist,
      inhibited ET-1 and ET-3 response. Our results show that ET-1 as well as ET-3 has
      an inhibitory neuromodulatory effect on NE release in the anterior hypothalamus
      mediated by the ET type B receptor and the involvement of a nitric oxide
      dependent pathway and GABA(A) receptors. ET-1 and ET-3 may thus diminish
      available NE in the synaptic gap leading to decreased noradrenergic activity.

PMID- 12184996
TI  - Development of beta-cell mass in fetuses of rats deprived of protein and/or
      energy in last trimester of pregnancy.
AB  - Fetal malnutrition is now proposed as a risk factor of later obesity and type II
      diabetes. We previously analyzed the long-term impact of reduced protein and/or
      energy intake strictly limited to the last week of pregnancy in Wistar rats.
      Three protocols of gestational malnutrition were used: 1) low-protein isocaloric
      diet (5 instead of 15%) with pair feeding to the mothers receiving the control
      diet, 2) restricted diet (50% of control diet), and 3) low protein-restricted
      diet (50% of low-protein diet). Only isolated protein restriction induced a long
      term beta-cell mass decrease. In the present study, we used the same protocols of
      food restriction to analyze their short-term impact (on day 21.5 of pregnancy) on
      beta-cell mass development. A 50% beta-cell mass decrease was present in the
      three restricted groups, but low-protein diet, either associated or not to energy
      restriction, increased fetal beta-cell insulin content. Among all the parameters
      analyzed to further explain our results, we found that the fetal plasma level of
      taurine was lowered by low-protein diet and was the main predictor of the fetal
      plasma insulin level (r = 0.63, P < 0.01). In conclusion, rat fetuses exposed to
      protein and/or energy restriction during the third part of pregnancy have a
      similar dramatic decrease in beta-cell mass, and their ability to recover beta
      cell mass development retardation depends on the type of malnutrition used.
      Moreover, our results support the hypothesis that taurine might play an important
      role in fetal beta-cell mass function.

PMID- 12184998
TI  - Prostaglandins that increase renin production in response to ACE inhibition are
      not derived from cyclooxygenase-1.
AB  - It is well known that nonselective, nonsteroidal anti-inflammatory drugs inhibit
      renal renin production. Our previous studies indicated that angiotensin
      converting enzyme inhibitor (ACEI)-mediated renin increases were absent in rats
      treated with a cyclooxygenase (COX)-2-selective inhibitor and in COX-2 -/- mice.
      The current study examined further whether COX-1 is also involved in mediating
      ACEI-induced renin production. Because renin increases are mediated by cAMP, we
      also examined whether increased renin is mediated by the prostaglandin E(2)
      receptor EP(2) subtype, which is coupled to G(s) and increases cAMP. Therefore,
      we investigated if genetic deletion of COX-1 or EP(2) prevents increased ACEI
      induced renin expression. Age- and gender-matched wild-type (+/+) and homozygous
      null mice (-/-) were administered captopril for 7 days, and plasma and renal
      renin levels and renal renin mRNA expression were measured. There were no
      significant differences in the basal level of renal renin activity from plasma or
      renal tissue in COX-1 +/+ and -/- mice. Captopril administration increased renin
      equally [plasma renin activity (PRA): +/+ 9.3 +/- 2.2 vs. 50.1 +/- 10.9; -/- 13.7
      +/- 1.5 vs. 43.9 +/- 6.6 ng ANG I x ml(-1) x h(-1); renal renin concentration:
      +/+ 11.8 +/- 1.7 vs. 35.3 +/- 3.9; -/- 13.0 +/- 3.0 vs. 27.8 +/- 2.7 ng ANG I x
      mg protein(-1) x h(-1); n = 6; P < 0.05 with or without captopril]. ACEI also
      increased renin mRNA expression (+/+ 2.4 +/- 0.2; -/- 2.1 +/- 0.2 fold control; n
      = 6-10; P < 0.05). Captopril led to similar increases in EP(2) -/- compared with
      +/+. The COX-2 inhibitor SC-58236 blocked ACEI-induced elevation in renal renin
      concentration in EP(2) null mice (+/+ 24.7 +/- 1.7 vs. 9.8 +/- 0.4; -/- 21.1 +/-
      3.2 vs. 9.3 +/- 0.4 ng ANG I x mg protein(-1) x h(-1); n = 5) as well as in COX-1
      -/- mice (SC-58236-treated PRA: +/+ 7.3 +/- 0.6; -/- 8.0 +/- 0.9 ng ANG I x ml(
      1) x h(-1); renal renin: +/+ 9.1 +/- 0.9; -/- 9.6 +/- 0.5 ng ANG I x mg protein(
      1) x h(-1); n = 6-7; P < 0.05 compared with no treatment). Immunohistochemical
      analysis of renin expression confirmed the above results. This study provides
      definitive evidence that metabolites of COX-2 rather than COX-1 mediate ACEI
      induced renin increases. The persistent response in EP(2) nulls suggests
      involvement of prostaglandin E(2) receptor subtype 4 and/or prostacyclin receptor
      (IP).

PMID- 12184997
TI  - Cyclooxygenase cloning in dogfish shark, Squalus acanthias, and its role in
      rectal gland Cl secretion.
AB  - The present studies were carried out with the aims to determine the cDNA sequence
      for cyclooxygenase (COX) in an elasmobranch species and to study its role in
      regulation of chloride secretion in the perfused shark rectal gland (SRG). With
      the use of long primers (43 bp) derived from regions of homology between
      zebrafish and rainbow trout COX-2 genes, a 600-bp product was amplified from SRG
      and was found to be almost equally homologous to mammalian COX-1 and COX-2 (65%).
      The full-length cDNA sequence was obtained by 5'-RACE and by analyzing an EST
      clone generated by the EST Project of the Mt. Desert Island Biological Laboratory
      Marine DNA Sequencing Center. The longest open reading frame encodes a 593-amino
      acid protein that has 68 and 64% homology to mammalian COX-1 and COX-2,
      respectively. The gene and its protein product is designated as shark COX (sCOX).
      The key residues in the active site (Try(385), His(388), and Ser(530)) are
      conserved between the shark and mammalian COX. sCOX contains Val(523) that has
      been shown to be a key residue determining the sensitivity to COX-2-specific
      inhibitors including NS-398. The mRNA of sCOX, detected by RT-PCR, was found in
      all tissues tested, including rectal gland, kidney, spleen, gill, liver, brain,
      and heart, but not in fin. In the perfused SRG, vasoactive intestinal peptide
      (VIP) at 5 nM induced rapid and marked Cl(-) secretion (basal: <250 microeq x h(
      1) x g(-1); peak response: 3,108 +/- 479 microeq x h(-1) x g(-1)). In the
      presence of 50 microM NS-398, both the peak response (2,131 +/- 307 microeq x h(
      1) x g(-1)) and the sustained response to VIP were significantly reduced. When NS
      398 was removed, there was a prompt recovery of chloride secretion to control
      values. In conclusion, we have cloned the first COX in an elasmobranch species
      (sCOX) and shown that sCOX inhibition suppresses VIP-stimulated chloride
      secretion in the perfused SRG.

PMID- 12184999
TI  - IGF-I binding in primary culture of muscle cells of rainbow trout: changes during
      in vitro development.
AB  - To characterize and study the variations of IGF-I binding during the development
      of trout muscle cells, in vitro experiments were conducted using myocyte
      cultures, and IGF-I binding assays were performed in three stages of cell
      development: mononuclear cells (day 1), small myotubes (day 4), and large
      myotubes (day 10). Binding experiments were done by incubating cells with IGF-I
      for 12 h at 4 degrees C. Specific IGF-I binding increased with the concentration
      of labeled IGF-I and reached a plateau at 32 pM. The displacement of cold human
      and trout IGF-I showed a very similar curve (EC(50) = 1.19 +/- 0.05 and 0.95 +/-
      0.05 nM, respectively). IGF binding proteins did not interfere significantly
      because displacement of labeled IGF-I by either cold trout recombinant IGF-I or
      Des (1-3) IGF-I resulted in similar curves. Insulin did not displace labeled IGF
      I even at very high concentrations (>1 microM), which indicates the specificity
      of IGF-I binding. The amount of receptor (R(0)) increased from 253 +/- 51 fmol/mg
      DNA on day 1 to 766 +/- 107 fmol/mg DNA on day 10. However, the affinity (K(d))
      of IGF-I receptors did not change significantly during this development (from
      1.29 +/- 0.19 to 0.79 +/- 0.13 nM). On the basis of our results, we conclude that
      rainbow trout muscle cells in culture express specific IGF-I receptors, which
      increase their number with development from mononuclear cells to large myotubes.

PMID- 12185000
TI  - Dynamic modulation of cerebrovascular resistance as an index of autoregulation
      under tilt and controlled PET(CO(2)).
AB  - Transfer function analysis of the arterial blood pressure (BP)-mean flow velocity
      (MFV) relationship describes an aspect of cerebrovascular autoregulation. We
      hypothesized that the transfer function relating BP to cerebrovascular resistance
      (CVRi) would be sensitive to low-frequency changes in autoregulation induced by
      head-up tilt (HUT) and altered arterial PCO(2). Nine subjects were studied in
      supine and HUT positions with end-tidal PCO(2) (PET(CO(2))) kept constant at
      normal levels: +5 and -5 mmHg. The BP-MFV relationship had low coherence at low
      frequencies, and there were significant effects of HUT on gain only at high
      frequencies and of PCO(2) on phase only at low frequencies. BP --> CVRi had
      coherence >0.5 from very low to low frequencies. There was a significant
      reduction of gain with increased PCO(2) in the very low and low frequencies and
      with HUT at the low frequency. Phase was affected by PCO(2) in the very low
      frequencies. Transfer function analysis of BP --> CVRi provides direct evidence
      of altered cerebrovascular autoregulation under HUT and higher levels of PCO(2).

PMID- 12185002
TI  - Periconceptional nutrition programs development of the cardiovascular system in
      the fetal sheep.
AB  - It has been proposed that fetal adaptations to intrauterine nutrient deprivation
      permanently reprogram the cardiovascular system. We investigated the impact of
      restricted periconceptional nutrition and/or restricted gestational nutrition on
      fetal arterial blood pressure (BP), heart rate, rate pressure product, and the
      fetal BP responses to ANG II and the angiotensin-converting enzyme inhibitor
      captopril during late gestation. Restricted periconceptional nutrition resulted
      in an increase in fetal mean arterial BP between 115 and 125 days gestation
      (restricted 41.5 +/- 2.8 mmHg, n = 12; control 38.5 +/- 1.5 mmHg, n = 13) and
      between 135 and 147 days gestation (restricted 50.5 +/- 2.2 mmHg, n = 8; control
      42.5 +/- 1.9 mmHg, n = 10) as well as an increase in the rate pressure product in
      twin, but not singleton, fetuses between 115 and 147 days gestation. Mean BP and
      fetal plasma ACTH were also positively correlated in twin, but not singleton,
      fetuses. This is the first demonstration that maternal undernutrition during the
      periconceptional period results in an increase in fetal arterial BP. This
      increase occurs concomitantly with an increase in fetal ACTH but is not dependent
      on activation of the fetal renin-angiotensin system.

PMID- 12185001
TI  - Interaction between muscarinic receptor subtype signal transduction pathways
      mediating bladder contraction.
AB  - M(3) muscarinic receptors mediate cholinergic-induced contraction in most smooth
      muscles. However, in the denervated rat bladder, M(2) receptors participate in
      contraction because M(3)-selective antagonists [para-fluoro-hexahydro-sila
      diphenidol (p-F-HHSiD) and 4-DAMP] have low affinities. However, the affinity of
      the M(2)-selective antagonist methoctramine in the denervated bladder is
      consistent with M(3) receptor mediating contraction. It is possible that two
      pathways interact to mediate contraction: one mediated by the M(2) receptor and
      one by the M(3) receptor. To determine whether an interaction exists, the
      inhibitory potencies of combinations of methoctramine and p-F-HHSiD for reversing
      cholinergic contractions were measured. In normal bladders, all combinations gave
      additive effects. In denervated bladders, synergistic effects were seen with the
      10:1 and 1:1 (methoctramine:p-F-HHSiD wt/wt) combinations. After application of
      the sarcoplasmic reticulum ATPase inhibitor thapsigargin to normal tissue, the
      10:1 and 1:1 ratios became synergistic, mimicking denervated tissue. Thus in
      normal bladders both M(2) and M(3) receptors can induce contraction. In the
      denervated bladder, the M(2) and the M(3) receptors interact in a facilitatory
      manner to mediate contraction.

PMID- 12185003
TI  - Glucocorticoid-mediated attenuation of the hsp70 response in trout hepatocytes
      involves the proteasome.
AB  - The physiological implication of elevated cortisol levels on cellular heat-shock
      protein 70 (hsp70) response was examined using primary cultures of rainbow trout
      (Oncorhynchus mykiss) hepatocytes. Trout hepatocytes treated with cortisol, the
      predominant glucocorticoid in teleosts, responded to the heat shock (+15 degrees
      C for 1 h) with a significant drop in hsp70 accumulation over a 24-h recovery
      period. [(35)S]methionine incorporation and pulse-chase studies confirmed that
      this cortisol impact was due to decreased hsp70 synthesis and not enhanced
      protein breakdown. Cortisol also significantly decreased glucocorticoid receptor
      (GR) expression in trout hepatocytes. This receptor downregulation was inhibited
      by the proteasomal inhibitors, lactacystin and MG-132, implying a role for the
      proteasome in GR downregulation by cortisol. Inhibiting the proteasome did not
      significantly modify heat-induced hsp70 accumulation in the absence of cortisol
      but significantly elevated hsp70 expression in the presence of cortisol in heat
      shocked trout hepatocytes. Taken together, our results suggest proteasome
      mediated GR degradation as a mechanism for the attenuation of hsp70 response by
      cortisol in heat-shocked hepatocytes.

PMID- 12185004
TI  - Decompensated hemorrhage activates serotonergic neurons in the subependymal
      parapyramidal region of the rat medulla.
AB  - According to prior evidence opioid and serotonin release by lower brain stem
      neurons may contribute to hemorrhage-induced sympathoinhibition (HISI). Here we
      seek direct evidence for the activation of opioidergic, GABAergic, or
      serotonergic neurons by severe hemorrhage in the medulla oblongata. Blood was
      withdrawn from awake rats (40-50% total volume) causing hypotension and profound
      initial bradycardia. Other rats received the vasodilator hydralazine, causing
      tachycardia and hypotension. Neuronal activation was gauged by the presence of
      Fos-immunoreactive (ir) nuclei after 2 h. Serotonergic, enkephalinergic, and
      GABAergic neurons were identified by the presence of a diagnostic enzyme or mRNA.
      Hemorrhaged rats had 30% fewer non-GABAergic Fos-ir neurons in the rostral
      ventrolateral medulla (RVLM) than hydralazine-treated rats, but they had six
      times more Fos-ir neurons within the subependymal parapyramidal nucleus (SEPPN).
      Fos-labeled SEPPN neurons were serotonergic (40-60%), GABAergic (31%),
      enkephalinergic (15%), or had mixed phenotypes. The data suggest that a reduced
      sympathoexcitatory drive from RVLM may contribute to HISI. SEPPN neuronal
      activation may also contribute to HISI or could mediate defensive
      thermoregulatory mechanisms triggered by hemorrhage-induced hypothermia.

PMID- 12185005
TI  - Lipopolysaccharide regulates proinflammatory cytokine expression in mouse
      myoblasts and skeletal muscle.
AB  - The purpose of the present study was to examine the regulation of tumor necrosis
      factor (TNF)-alpha and interleukin (IL)-6 by lipopolysaccharide (LPS) in C2C12
      myoblasts and mouse skeletal muscle. LPS produced dose- and time-dependent
      increases in TNF-alpha and IL-6 mRNA content in C2C12 myoblasts. The LPS-induced
      cytokine response could be mimicked by peptidoglycan from the cell wall of
      Staphylococcus aureus but not by zymosan A, a cell wall component from
      Saccharomyces cerevisiae. Ongoing protein synthesis was not necessary for the
      increase in the two cytokine mRNAs. The transcriptional inhibitor 5,6-dichloro
      beta-D-ribofuranosyl-benzimidazole blocked LPS-stimulated IL-6 mRNA expression
      without changing its mRNA half-life. The anti-inflammatory glucocorticoid
      dexamethasone selectively blocked LPS-stimulated IL-6 mRNA accumulation but not
      TNF-alpha. In contrast, the proteasomal inhibitor MG-132 blocked TNF-alpha mRNA
      expression but not IL-6. Exposure of myoblasts to LPS was associated with a rapid
      decrease in the inhibitor of nuclear factor-kappaB (I kappaB, alpha, and
      epsilon), and this response was also blocked by MG-132. Treatment of myocytes
      with IL-1 or TNF-alpha also increased IL-6 mRNA content, but the increase in IL-6
      mRNA due to LPS could not be prevented by pretreatment with antagonists to either
      IL-1 or TNF. Under in vivo conditions, LPS increased the plasma concentration of
      TNF-alpha and IL-6 and stimulated the accumulation of their mRNAs in multiple
      tissues including skeletal muscle from wild-type mice. In contrast, the ability
      of LPS to stimulate the same cytokines was markedly decreased in mice that harbor
      a mutation in the Toll-like receptor 4. Our data suggest that LPS stimulates
      cytokine expression not only in classical immune tissues but also in skeletal
      muscle.

PMID- 12185006
TI  - Antihypertensive effect of mechanism-based inhibition of renal arachidonic acid
      omega-hydroxylase activity.
AB  - The cytochrome P-450 eicosanoid 20-hydroxyeicosatetraenoic acid (20-HETE) is a
      potent vasoconstrictor that is implicated in the regulation of blood pressure.
      The identification of selective inhibitors of renal 20-HETE formation for use in
      vivo would facilitate studies to determine the systemic effects of this
      eicosanoid. We characterized the acetylenic fatty acid sodium 10-undecynyl
      sulfate (10-SUYS) as a potent and selective mechanism-based inhibitor of renal 20
      HETE formation. A single dose of 10-SUYS caused an acute reduction in mean
      arterial blood pressure in 8-wk-old spontaneously hypertensive rats. The decrease
      in mean arterial pressure was maximal 6 h after 10-SUYS treatment (17.9 +/- 3.2
      mmHg; P < 0.05), and blood pressure returned to baseline levels within 24 h after
      treatment. Treatment with 10-SUYS was associated with a decrease in urinary 20
      HETE formation in vivo and attenuation of the vasoconstrictor response of renal
      interlobar arteries to ANG II in vitro. These results provide further evidence
      that 20-HETE plays an important role in the regulation of blood pressure in the
      spontaneously hypertensive rat.

PMID- 12185007
TI  - Potential switch from eupnea to fictive gasping after blockade of glycine
      transmission and potassium channels.
AB  - This study evaluated possible neuronal mechanisms responsible for the transition
      from normal breathing (eupnea) to gasping. We hypothesized that a blockade of
      both inhibitory glycinergic synaptic transmission and potassium channels,
      combined with an increase in extracellular concentration of potassium, would
      induce a switch from an eupneic respiratory pattern to gasping. Efferent
      activities of the phrenic, vagal, and hypoglossal nerves were recorded during
      eupnea and ischemia-induced gasping in a perfused in situ preparation of the
      juvenile rat (4-6 wk of age). To block potassium channels, 4-aminopyridine (4-AP,
      1-10 microM) was administered. Strychnine (0.2-0.6 microM) was used to block
      glycinergic neurotransmission. After administrations of 4-AP, excess
      extracellular potassium (10.25-17.25 mM), and strychnine, the incrementing
      pattern of eupneic phrenic activity was altered to a decrementing discharge.
      Hypoglossal and vagal activities became concentrated to the period of the phrenic
      burst with expiratory activity being reduced or eliminated. These changes in
      neural activities were similar to those in ischemia-induced gasping. Results are
      consistent with the concept that the elicitation of gasping represents a switch
      from a network-based rhythmogenesis for eupnea to a pacemaker-driven mechanism.

PMID- 12185008
TI  - Superoxide dismutase and oxidative stress in Dahl salt-sensitive and -resistant
      rats.
AB  - The roles of oxidative stress and renal superoxide dismutase (SOD) levels and
      their association with renal damage were studied in Dahl salt-sensitive (S) and
      salt-resistant (R)/Rapp strain rats during changes in Na intake. After 3 wk of a
      high (8%)-Na diet in S rats, renal medullary Cu/Zn SOD was 56% lower and Mn SOD
      was 81% lower than in R high Na-fed rats. After 1, 2, and 3 wk of high Na,
      urinary excretion of F(2)-isoprostanes, an index of oxidative stress, was
      significantly greater in S rats compared with R rats. Plasma F(2)-isoprostane
      concentration increased in the 2-wk S high Na-fed group. After 3 wk, renal
      cortical and medullary superoxide production was significantly increased in Dahl
      S rats on high Na intake, and urinary protein excretion, an index of renal
      damage, was 273 +/- 32 mg/d in S high Na-fed rats and 35 +/- 4 mg/d in R high Na
      fed rats (P < 0.05). In conclusion, salt-sensitive hypertension in the S rat is
      accompanied by marked decreases in renal medullary SOD and greater renal
      oxidative stress and renal damage than in R rats.

PMID- 12185009
TI  - Transecting the gustatory branches of the facial nerve impairs NH(4)Cl vs. KCl
      discrimination in rats.
AB  - Ammonium and potassium chloride share a common taste quality and an amiloride
      insensitive route of transduction. An amiloride-sensitive pathway might also be
      partially activated by these salts, although very few studies have reported
      effects of amiloride on nonsodium salt perception. This experiment was designed
      to determine 1) whether rats could discriminate KCl from NH(4)Cl and, if
      discrimination was evident, whether performance was impaired with 2) amiloride or
      3) gustatory nerve transection. Rats were trained to discriminate KCl from
      NH(4)Cl (n = 8) and NaCl from NH(4)Cl (n = 8). Amiloride (100 microM) impaired
      NaCl vs. NH(4)Cl but not KCl vs. NH(4)Cl performance, whereas both groups showed
      significant impairments after transection of the chorda tympani (CT) and greater
      superficial petrosal (GSP) branches of the facial nerve. This suggests that rats
      can discriminate between KCl and NH(4)Cl and that this discrimination does not
      rely on an amiloride-sensitive mechanism but does depend on the CT and/or GSP
      nerves. This experiment supports the hypothesis that the facial nerve is
      important for salt taste recognition and discrimination.

PMID- 12185010
TI  - Heart rate-arterial blood pressure relationship in conscious rat before vs. after
      spinal cord transection.
AB  - This experiment quantified the initial disruption and subsequent adaptation of
      the blood pressure (BP)-heart rate (HR) relationship after spinal cord
      transection (SCT). BP and HR were recorded for 4 h via an implanted catheter in
      neurally intact, unanesthetized rats. The animals were then anesthetized, and
      their spinal cords were severed at T(1)-T(2) (n = 5) or T(4)-T(5) (n = 6) or sham
      lesioned (n = 4). BP was recorded for 4 h daily over the ensuing 6 days. The
      neurally intact rat showed a positive cross correlation, with HR leading BP at
      the peak by 1.8 +/- 0.8 (SD) s. The cross correlation in unanesthetized rats (n =
      2) under neuromuscular blockade was also positive, with HR leading. After SCT at
      T(1)-T(2), the cross correlation became negative, with BP leading HR, and did not
      change during the next 6 days. The cross correlation also became negative 1-3
      days after SCT at T(4)-T(5), but in four rats by day 6 and thereafter the cross
      correlation progressively reverted to a positive value. We propose that the
      positive cross correlation with HR leading BP in the intact rat results from an
      open-loop control that depends on intact supraspinal input to sympathetic
      preganglionic neurons in the spinal cord. After descending sympathetic pathways
      were severed at T(1)-T(2), the intact vagal pathway to the sinoatrial node
      dominated BP regulation via the baroreflex. We suggest that reestablishment of
      the positive correlation after SCT at T(4)-T(5) was attributable to the surviving
      sympathetic outflow to the heart and upper vasculature reasserting some effective
      function, perhaps in association with decreased spinal sympathetic hyperreflexia.
      The HR-BP cross correlation may index progression of sympathetic dysfunction in
      pathological processes.

PMID- 12185011
TI  - Antihypertensive effects of chronic anti-TGF-beta antibody therapy in Dahl S
      rats.
AB  - This study examined the role of transforming growth factor-beta (TGF-beta) in the
      development of hypertension and renal disease in 9-wk-old male Dahl salt
      sensitive (Dahl S) rats fed an 8% NaCl diet for 3 wk. The rats received an
      intraperitoneal injection of a control or an anti-TGF-beta antibody (anti-TGF
      beta Ab) every other day for 2 wk. Mean arterial pressure was significantly lower
      in Dahl S rats treated with anti-TGF-beta Ab (177 +/- 3 mmHg, n = 12) than in
      control rats (190 +/- 4 mmHg, n = 17). Anti-TGF-beta Ab therapy also reduced
      proteinuria from 226 +/- 20 to 154 +/- 16 mg/day. Renal blood flow, cortical
      blood flow, and creatinine clearance were not significantly different in control
      and treated rats; however, medullary blood flow was threefold higher in the
      treated rats than in the controls. Despite the reduction in proteinuria, the
      degree of glomerulosclerosis and renal hypertrophy was similar in control and
      anti-TGF-beta Ab-treated rats. Renal levels of TGF-beta1 and -beta2, alpha-actin,
      type III collagen, and fibronectin mRNA decreased in rats treated with anti-TGF
      beta Ab. To examine whether an earlier intervention with anti-TGF-beta Ab would
      confer additional renoprotection, these studies were repeated in a group of 6-wk
      old Dahl S rats. Anti-TGF-beta Ab therapy significantly reduced blood pressure,
      proteinuria, and the degree of glomerulosclerosis and renal medullary fibrosis in
      this group of rats. The results indicate that anti-TGF-beta Ab therapy reduces
      blood pressure, proteinuria, and the renal injury associated with hypertension.

PMID- 12185012
TI  - The caudal pressor area of the rat: its precise location and projections to the
      ventrolateral medulla.
AB  - Investigators have demonstrated pressor areas in the medullas of various species.
      The present study precisely localized the pressor area in the caudal medulla of
      the rat and determined its projections to the caudal and rostral ventrolateral
      medulla. The caudal medulla first was mapped grossly in rats with injections (30
      nl) of glutamate (30-, 15-, and 7.5-nmol doses) placed 0.5, 1.0, and 1.5 mm
      caudal to the calamus scriptorius, 1.0, 1.5, and 2.0 mm lateral to the midline,
      and 1.8, 1.7, and 1.6 mm ventral to the dorsal medullary surface, respectively,
      and their arterial pressures were recorded. One of these nine injections showed
      significant increases in arterial pressure. We micromapped this area with a total
      of 27 injections of glutamate (10 nl; 5 nmol) placed 300 microm apart at 3
      different dorsoventral levels. This micromapping study pinpointed the precise
      location of caudal pressor area (CPA) neurons in a restricted region lateral to
      the caudal end of the lateral reticular nucleus and ventromedial to the medullary
      dorsal horn near the level of the pyramidal decussation. Injections of glutamate
      into this spot, 1.0 mm caudal to the calamus scriptorius, 2.0 mm lateral to the
      midline, and 1.7 mm ventral from the dorsal surface of the medulla, induced
      significant increases in arterial pressure. The neuroanatomic connections of
      neurons in the CPA to the ventrolateral medulla were then investigated with
      iontophoretic injections of either the anterograde tracer biotinylated dextran
      amine (BDA) made into the CPA or the retrograde tracer FluoroGold (FG) injected
      into either the caudal or rostral ventrolateral medulla. BDA injections resulted
      in bouton-laden fibers throughout both caudal and rostral portions of the
      ventrolateral medulla. Either of the FG injections resulted in numerous spindle
      shaped neurons interspersed between the longitudinal fiber bundles running
      through the CPA area. The proximity of the CPA neurons to the A1
      catecholaminergic cell group is discussed.

PMID- 12185013
TI  - Distribution of aquaporins in the colon of Octodon degus, a South American desert
      rodent.
AB  - Octodon degus is a desert rodent of northern Chile, adapted to survive with a
      limited supply of water. This rodent has a high degree of fecal dehydration,
      related to colon water absorption. With the hypothesis that aquaporins (AQPs)
      might be present in the colon epithelium of O. degus and involved in fluid
      absorption, we studied colon water absorption in vivo and the distribution of
      AQPs and Na(+) transporters by immunocytochemistry. AQP-1 was found in apical and
      basolateral membranes of surface-absorptive and crypt epithelial cells. AQP-8 was
      found in the cytoplasm of enterocytes of surface colon. AQP-3 immunolabeling, on
      the other hand, was absent from the epithelium but present in a subepithelial
      fibroblast layer, pericryptal cells, and muscularis mucosae. The hydration state
      did not modify the amount of immunostaining for any of the AQPs. Colon water
      absorption was markedly decreased by the mercurial agent p
      chloromercuribenzenesulfonic acid and was not affected by water deprivation. The
      NHE3 isoform of Na(+)/H(+) exchanger and alpha-1 subunit of the Na(+)-K(+)-ATPase
      were found in apical and basolateral membranes of surface-absorptive cells,
      respectively. These results suggest that colon water absorption is mostly
      transcellular and mediated by water channels like AQP-1. Apical Na(+)/H(+)
      exchanger and basolateral Na(+)-K(+)-ATPase in surface cells could be part of the
      Na(+) absorption pathway. It is hypothesized that this transport is necessary to
      provide an osmotic gradient for water absorption. The roles of AQP-8 and AQP-3 in
      water absorption remain to be established.

PMID- 12185014
TI  - Sample entropy analysis of neonatal heart rate variability.
AB  - Abnormal heart rate characteristics of reduced variability and transient
      decelerations are present early in the course of neonatal sepsis. To investigate
      the dynamics, we calculated sample entropy, a similar but less biased measure
      than the popular approximate entropy. Both calculate the probability that epochs
      of window length m that are similar within a tolerance r remain similar at the
      next point. We studied 89 consecutive admissions to a tertiary care neonatal
      intensive care unit, among whom there were 21 episodes of sepsis, and we
      performed numerical simulations. We addressed the fundamental issues of optimal
      selection of m and r and the impact of missing data. The major findings are that
      entropy falls before clinical signs of neonatal sepsis and that missing points
      are well tolerated. The major mechanism, surprisingly, is unrelated to the
      regularity of the data: entropy estimates inevitably fall in any record with
      spikes. We propose more informed selection of parameters and reexamination of
      studies where approximate entropy was interpreted solely as a regularity measure.

PMID- 12185015
TI  - What suppresses fever in pregnancy near term?

PMID- 12185017
TI  - Imaging: a sisyphean search for the elusive tissue signature.

PMID- 12185016
TI  - Suppression of fever at near term is associated with reduced COX-2 protein
      expression in rat hypothalamus.
AB  - The fever response is blunted at near term. As the enzyme cyclooxygenase-2 (COX
      2) plays a critical role in fever development, we measured its expression in rat
      hypothalamus during pregnancy and lactation. Western blot analysis revealed a 72
      kDa COX-2-immunoreactive band in non-immune-challenged, pregnant rats at day 15
      of pregnancy. In contrast, it was almost undetectable at near term and at
      lactation day 5. COX-2 was significantly induced at the 15th day of pregnancy and
      at the 5th lactating day after intraperitoneal lipopolysaccharide (50 microg/kg).
      However, this COX-2 induction was significantly reduced at near term compared
      with values before and after term. The protein levels of the EP3 receptor in the
      hypothalamus, one of the prostaglandin E(2) (PGE(2)) receptors suggested to be a
      key receptor for fever induction, were unaffected throughout the pregnancy and
      lactation in both non-immune-challenged and lipopolysaccharide-treated rats.
      These data suggest that suppression of fever at near term is associated with a
      significantly reduced induction of COX-2 by lipopolysaccharide, resulting in a
      reduced production of PGE(2). Altered expression of the EP3 receptor does not
      seem to be involved in this fever refractoriness at near term.

PMID- 12185018
TI  - Heart in brain: normal variation of dorsum sellae.

PMID- 12185019
TI  - Imaging of adrenal incidentalomas: current status.

PMID- 12185020
TI  - Proximate cause.

PMID- 12185022
TI  - Review and interpretation of MR imaging studies with PACS: creating uniform
      series descriptors for radiologists and referring physicians.
AB  - OBJECTIVE: We sought to identify a limited set of standardized descriptors for
      various MR image series on a picture archiving and communications system (PACS)
      and to apply these descriptors to both existing and newly acquired MR images.
      CONCLUSION: Of the 47,028 MR image series in our PACS, approximately 2500 had
      been assigned unique descriptors, and nearly 82% of the descriptors had a
      frequency of appearance of less than 5%. We reduced the number of descriptors to
      146 without loss of essential information. Use of standardized descriptors may
      facilitate identification of various MR image series.

PMID- 12185023
TI  - MyPACS.net: a Web-based teaching file authoring tool.
AB  - OBJECTIVE: We sought to develop a Web service that would easily allow
      radiologists to create their own online teaching file cases from any Web browser.
      CONCLUSION: We created MyPACS, a hosted teaching file authoring tool that allows
      easy uploading of images and descriptive information from any computer with Web
      access. Radiologists may designate their cases to be public or private (viewable
      only by the case author), and cases may be retrieved on searching for multiple
      parameters.

PMID- 12185024
TI  - Tunable monochromatic X rays: a new paradigm in medicine.

PMID- 12185025
TI  - Using a dopamine type 1A receptor agonist in high-risk patients to ameliorate
      contrast-associated nephropathy.
AB  - OBJECTIVE: The objective of our study was to evaluate the effects of fenoldopam
      mesylate, a dopamine type 1A receptor agonist and a potent renal vasodilator that
      markedly increases renal blood flow, on kidney function of patients who were
      receiving iodinated contrast material for an interventional procedure and thought
      to be at high risk of contrast-associated nephropathy. MATERIALS AND METHODS: We
      retrospectively reviewed the records of all patients who received fenoldopam
      mesylate to determine the acute and, when possible, the longer term effects on
      kidney function. RESULTS: Twenty-nine cases were reviewed. The average serum
      creatinine value before contrast administration was 2.55 mg/dL (range, 1.3-5.8
      mg/dL) [corrected]. Twenty-four hours after contrast administration, serum
      creatinine was measured in 28 of the 29 patients. The serum creatinine values had
      decreased in 16 of the 28 patients by an average of 0.55 mg/dL [corrected]. In
      nine patients, the serum creatinine value had not changed. Two of the three
      increases in the serum creatinine value appear to have been caused primarily by
      problems that did not involve the contrast material. CONCLUSION: The use of
      fenoldopam mesylate at appropriate doses offers patients at high risk for
      contrast-associated nephropathy a chance to avoid this complication. To learn the
      extent and true nature of the effect of fenoldopam mesylate in this patient
      population requires a rigorous scientific trial, which is currently underway.

PMID- 12185026
TI  - Placement of vena cava filters: factors affecting technical success and immediate
      complications.
AB  - OBJECTIVE: The goal of this study was to evaluate factors affecting technical
      success and the immediate complications of placement of vena cava filters.
      MATERIALS AND METHODS: The medical records of 148 consecutive patients who
      underwent filter placement between December 1995 and February 1999 were
      retrospectively reviewed for cavography, technical success, complications, and
      operator specialty. RESULTS: The records of 143 filter placements in 142 patients
      were complete (one patient underwent two placements). One hundred twenty filter
      placements were preceded by cavography, and 23 were not. Three misplacements
      (2.5%) were preceded by cavography and 10 (43%) were not (p<0.0001). One hundred
      fourteen filter placements were performed by radiologists and 29 by surgeons.
      Cavography was performed before 98% of placements by radiologists but in only 28%
      of placements by surgeons (p<0.0001). Filter misplacement occurred in 12
      placements (41%) by surgeons and in only one (0.9%) by radiologists (p<0.0001).
      Major complications occurred in three placements (10%) by surgeons and in none of
      the placements by radiologists (p<0.01). CONCLUSION: Vena cava filters were
      placed with greater technical success and fewer complications when preceded by
      cavography. Radiologists placed filters with greater technical success and fewer
      complications than surgeons, which may be the result of radiologists generally
      having more training and more familiarity with imaging-guided procedures and
      adhering more to cavography protocol. A credentialing requirement for physician
      operators and evaluation using quality improvement standards may be advisable.

PMID- 12185027
TI  - Indications for, timing of, and results of catheter-based treatment of traumatic
      injury to the aorta.
AB  - OBJECTIVE: The optimal treatment for and timing of surgery to repair traumatic
      aortic injury are still controversial. Endovascular treatment is a viable option
      in patients with both acute and chronic aortic trauma. However, appropriate
      patient selection criteria, treatment timing, and long-term durability of
      endovascular repair remain to be defined. We sought to identify appropriate
      selection criteria and optimal timing of treatment as well as to assess the long
      term durability of endovascular repair. SUBJECTS AND METHODS: From July 1997 to
      December 2001, 19 patients with traumatic aortic injury (11 patients with acute
      and eight with chronic injuries) were selected for endovascular treatment. In all
      patients, the lesions were sited at the proximal segment of the descending aorta
      at a distance of 10 +/- 17 mm (mean +/- SD) from the left subclavian artery. Nine
      of the patients with acute injuries were treated after clinical stabilization of
      other severe associated lesions, whereas two patients, in whom hemodynamic and
      imaging findings suggested an impending rupture, received emergency treatment.
      Single-detector helical CT or MR imaging was used for patient selection and stent
      graft customization before treatment and for evaluation of patients during the
      follow-up period. RESULTS: Endovascular stent positioning was successful in all
      patients. None of the patients developed complications. Aneurysm exclusion and
      shrinkage were confirmed at followup examinations. A partial covering of the
      subclavian artery occurred in six patients without interrupting the blood flow.
      All patients remain asymptomatic after a mean follow-up period of 20 months
      (range, 1-56 months). CONCLUSION: Endovascular repair represents an alternative,
      minimally invasive treatment, particularly suitable for use in patients with
      traumatic aortic injuries. The decision of whether to provide immediate emergency
      treatment or to delay treatment should be based on the lesion characteristics on
      imaging and clinical findings. The durability of treatment seems to be related to
      the absence of alteration to the aortic wall at the extremities.

PMID- 12185028
TI  - Histomorphometric evaluation of (198)Au endovascular brachytherapy in a renal
      artery restenosis model in rabbits.
AB  - OBJECTIVE: The main mid-term complication of percutaneous transluminal
      angioplasty of the renal artery is restenosis, which occurs in up to 50% of
      patients. Although no pharmacologic agent to date has been effective in
      preventing restenosis, both beta-ray emitters and gamma-ray emitters used in
      endovascular brachytherapy have been shown to reduce coronary restenosis. The
      objectives of this study were to evaluate the efficacy of (198)Au endovascular
      brachytherapy in preventing restenosis after percutaneous transluminal renal
      angioplasty and to determine the radiation dose to the operator. MATERIALS AND
      METHODS: Twenty-one New Zealand white rabbits (10 females and 11 males) weighing
      an average of 3.5 kg (range, 3.2-3.8 kg) who had been fed a normal diet underwent
      bilateral 33% overdilatation with deendothelialization of the renal arteries.
      After 7 weeks, the induced renal artery stenoses were treated by percutaneous
      transluminal renal angioplasty. The rabbits were randomly assigned to one of
      three groups before receiving endovascular 25-Gy irradiation at a radial 2.0-mm
      depth with a 0.5 x 15 mm (198)Au wire (106 MBq). The right renal artery was
      irradiated in group A; the left, in group B. The rabbits in group C randomly
      received a right- or left-sided dummy wire. Operator exposure to radiation was
      measured using thermoluminescent dosimeters and ionization chambers. The rabbits
      were sacrificed after 3 weeks. The aorta and renal arteries were perfusion-fixed.
      The renal arteries were removed for histologic and histomorphometric study.
      RESULTS: Forty-two renal arteries were cut into a series of 4- micro m-thick
      slices. Five arteries were thrombosed (two in the irradiated group and three in
      the control group, p > 0.05). In the patent arteries (n = 37), the average
      neointimal area was 0.068 mm(2) (range, 0.009-0.234 mm(2)) in 15 irradiated
      segments (315 slices total), whereas the average neointimal area was 0.135 mm(2)
      (range, 0.016-0.324 mm(2)) in 22 control segments (462 slices total) (analysis of
      variance, p < 0.009), showing a percentage area of restenosis of 10.4% in
      irradiated arteries and 43.4% in non-irradiated arteries (p < 0.0003). Radiation
      dose per procedure to the operator was 0.034 mSv in the index finger, 0.024 mSv
      in the wrist, and undectable in the body. CONCLUSION: Endovascular brachytherapy
      with (198)Au appears to inhibit early renal artery restenosis and exposes the
      operator to a safe level of radiation.

PMID- 12185029
TI  - Using 6-mm Cutting Balloon angioplasty in patients with resistant peripheral
      artery stenosis: preliminary results.
AB  - OBJECTIVE: The objective of this study was to assess the efficacy of 6-mm Cutting
      Balloon angioplasty in patients with resistant peripheral stenoses caused by
      neointimal hyperplasia or irradiation-induced arteriopathy in vascular
      territories that are not amenable for use of the smaller Cutting Balloons that
      are used in cardiology. CONCLUSION: Peripheral Cutting Balloon angioplasty with
      the new 6-mm Cutting Balloon device proved useful in the short term for treatment
      of peripheral arterial stenoses resistant to conventional angioplasty.

PMID- 12185031
TI  - Ovarian varices in healthy female kidney donors: incidence, morbidity, and
      clinical outcome.
AB  - OBJECTIVE: Kidney donation is associated with ligation of the ovarian vein and is
      comparable to ovarian vein embolization. We evaluated the incidence, morbidity,
      and clinical outcome of ovarian varices in healthy female kidney donors before
      and 6 months after nephrectomy. MATERIALS AND METHODS: Between 1994 and 2001, 273
      healthy female kidney donors underwent preoperative abdominal aortography. The
      study group consisted of 27 women (9.9%) in whom retrograde flow in an
      incompetent left ovarian vein was noted during the venous phase of imaging. All
      patients underwent left nephrectomy with left ovarian vein ligation. Only women
      with retrograde flow in the left ovarian vein were asked to complete a
      questionnaire about the incidence and intensity of pelvic pain before and 6
      months after nephrectomy. RESULTS: Twenty-two of the 27 left-kidney donors with
      retrograde flow in the ovarian vein were available for follow-up. Thirteen (59%)
      of those 22 reported chronic pelvic pain. After nephrectomy, the pelvic pain
      completely resolved in seven (54%), improved in three (23%), and persisted in
      three (23%). CONCLUSION: Our study found a 9.9% prevalence of ovarian varices in
      the general population. Our findings suggest that more than half (59%) the
      patients with ovarian varices have pelvic congestion syndrome and that most (77%)
      of them might benefit from ovarian vein embolization or ligation.

PMID- 12185032
TI  - Percutaneous CT-guided drainage of splenic abscess.
AB  - OBJECTIVE: The objective of our study was to determine the current role of
      percutaneous CT-guided drainage as an alternative to surgical treatment of
      splenic abscesses. CONCLUSION: Splenic abscess is an uncommon entity that can be
      treated percutaneously. CT-guided drainage of splenic abscess seems to be a safe
      and effective alternative to surgery, allowing preservation of the spleen.

PMID- 12185033
TI  - Celiac plexus block: a palliative tool underused by radiologists.

PMID- 12185034
TI  - Giant bilateral inflammatory pseudotumor arising along the arterial sheath of the
      lower extremities.

PMID- 12185035
TI  - MR imaging of the knee: findings in asymptomatic collegiate basketball players.
AB  - OBJECTIVE: The purpose of our study was to evaluate the knees of asymptomatic
      high-level collegiate basketball players before the beginning of the basketball
      season to gain an understanding of nonclinical findings in this patient
      population. SUBJECTS AND METHODS: Bilateral knee MR imaging examinations of 17
      varsity basketball players (12 men and five women) were performed before
      basketball season began. All of the subjects were imaged on a 1.5-T magnet. The
      MR imaging studies were reviewed by two musculoskeletal radiologists. Structures
      analyzed were the menisci, ligaments, cartilage, plicae, and bone marrow. The
      presence of a joint effusion was also noted. RESULTS: Fourteen (41%) of the 34
      knees had bone marrow edema, eight (24%) showed signal in the patellar tendon,
      and 14 (41%) had abnormal cartilage signal or a focal abnormality. Twelve (35%)
      of the 34 knees showed a joint effusion. Two knees (6%) showed abnormal signal
      along the infrapatellar plica. Four knees (12%) were noted to have a discoid
      meniscus. CONCLUSION: An MR examination of the knees of high-level collegiate
      basketball players may show changes unique to this population. The changes seen
      on MR imaging in these athletes may be asymptomatic abnormalities. For instance,
      changes suggestive of patellar tendinopathy were identified in these asymptomatic
      subjects.

PMID- 12185036
TI  - Grade 2C signal in the meniscus [correction of mensicus] on MR imaging of the
      knee.
AB  - OBJECTIVE: The objective of our study was to evaluate the clinical significance
      of grade 2C meniscal [corrected] signal (an extensive triangular or wedge-shaped
      signal that does not reach the surface on more than one image) on MR imaging of
      the knee. MATERIALS AND METHODS: Review of 1106 MR imaging reports over 2 years
      revealed 88 patients with menisci described as containing triangular, wedge
      shaped, extensive, or grade 2C signal. Image review by consensus of two
      radiologists found 34 menisci in 29 patients that fit criteria for grade 2C
      signal. Seven menisci containing grade 2C signal were evaluated with arthroscopy.
      An additional three patients with grade 2C meniscal signal with arthroscopic
      correlation were identified from 4 previous years. RESULTS: Prevalence of grade
      2C signal was 1.5% (34/2212 menisci). Seven (21%) of these 34 menisci had
      subsequent arthroscopy and three of these had meniscal tears. Including the three
      additional menisci with grade 2C signal from 4 previous years, five (50%) of 10
      menisci with grade 2C signal were torn at arthroscopy. No difference was noted
      between torn and intact menisci in the number of images with grade 2C signal. In
      patients with tears, the range was three to 10 images (mean, 6.6 images) compared
      with a range of two to 10 images (mean, 6.6 images) in patients without tears.
      The maximal percentage of area of abnormal signal in patients with tears ranged
      from 70% to 90% (mean, 80%) compared with a range of 60-90% (mean, 82%) in
      patients without tears. The patient age range was 23-64 years (mean, 47 years) in
      patients with tears and 16-67 years (mean, 47 years) in patients without tears.
      CONCLUSION: Grade 2C meniscal signal has a low incidence. Although half of
      patients with symptoms meriting arthroscopy have tears, most patients with grade
      2C signal are not treated with arthroscopy.

PMID- 12185037
TI  - Humeral avulsions of the glenohumeral ligament: imaging features and a review of
      the literature.
AB  - OBJECTIVE: We describe the radiologic findings of the humeral avulsion of the
      glenohumeral ligament (HAGL lesion) and its commonly associated injuries.
      MATERIALS AND METHODS: A retrospective review of six cases of HAGL lesion
      diagnosed at our institution from October 1996 to February 2001 was performed. We
      reviewed the radiology reports, radiologic examinations, medical records, and
      operative notes. All patients had undergone radiography, and four patients had
      undergone MR imaging of the shoulder before diagnostic arthroscopy. RESULTS: All
      the patients were men who ranged in age from 19 to 41 years (mean, 26 years).
      Four patients (67%) had an anterior shoulder dislocation. Three of the HAGL
      lesions (50%) were detected on radiologic examinations, either by radiography or
      MR imaging. One patient had a bony HAGL. All patients had associated injuries.
      The most common associated abnormalities were osteochondral injury of the humeral
      head (n = 3), rotator cuff tear (n = 3), Bankart lesion (n = 3), Hill-Sachs
      lesion (n = 2), avulsion of the middle glenohumeral ligament (n = 1), partial
      tear of the biceps brachii tendon (n = 1), and comminuted fracture of the
      clavicle (n = 1). CONCLUSION: With an incidence of 7.5% and 9.4% in two large
      series of patients, the HAGL lesion is an important cause of anterior instability
      of the glenohumeral joint. The majority (68%) of patients with an HAGL lesion
      have associated injuries.

PMID- 12185038
TI  - Rapidly destructive osteoarthritis of the hip: MR imaging findings.
AB  - OBJECTIVE: The aim of our study was to describe the MR imaging findings in
      patients with rapidly destructive osteoarthritis of the hip. CONCLUSION: The key
      MR imaging features of rapidly destructive hip osteoarthritis include joint
      effusion (100%), bone marrow edemalike pattern in the femoral head and neck
      (100%) or acetabulum (83%) or both, femoral head flattening (92%), and cystlike
      subchondral defects (83%). Additional findings are low-signal-intensity lines
      (33%) in the femoral epiphysis, bandlike areas of low signal intensity in the
      upper pole of the femoral head (8%), and focal signal abnormalities in the
      adjacent soft tissues (33%) on short tau inversion recovery MR images, fat
      suppressed T2-weighted MR images, and fat-suppressed gadolinium-enhanced T1
      weighted MR images.

PMID- 12185039
TI  - Revascularization of avascular necrosis of the capitate bone.

PMID- 12185040
TI  - Natural course of an intraosseous pneumatocyst of the cervical spine.

PMID- 12185042
TI  - Clinical comparison of full-field digital mammography and screen-film mammography
      for detection of breast cancer.
AB  - OBJECTIVE: The purpose of this work is to compare full-field digital mammography
      and screen-film mammography for the detection of breast cancer in a screening
      population. SUBJECTS AND METHODS: Full-field digital mammography was performed in
      addition to screen-film mammography in 6736 examinations of women 40 years old
      and older presenting for screening mammography at either of two institutions. Two
      views of each breast were acquired with each technique. The digital and screen
      film mammograms were each interpreted independently. In addition to a clinical
      assessment, each finding was assigned a probability of malignancy for use in
      receiver operating characteristic analysis. In cases in which the digital and
      screen-film interpretations differed, a side-by-side analysis was performed to
      determine the reasons for the discrepancy. With few exceptions, findings detected
      on either technique were evaluated with additional imaging and, if warranted,
      biopsy. RESULTS: Additional evaluation was recommended on at least one technique
      in 1467 cases. These additional evaluations led to 181 biopsies and the detection
      of 42 cancers. Nine cancers were detected only on digital mammography, 15 were
      detected only on screen-film mammography, and 18 were detected on both. The
      difference in cancer detection is not statistically significant (p > 0.1).
      Digital mammography resulted in fewer recalls than did screenfilm mammography
      (799 vs 1007, p < 0.001). The difference between the receiver operating
      characteristic curve area for digital (0.74) and screen-film (0.80) mammography
      was not significant (p > 0.1). Reasons for discrepant interpretations of cancer
      were approximately equally distributed among those relating to lesion
      conspicuity, lesion appearance, and interpretation. CONCLUSION: No significant
      difference in cancer detection was observed between digital mammography and
      screen-film mammography. Digital mammography resulted in fewer recalls than did
      screen-film mammography.

PMID- 12185043
TI  - To excise or to sample the mammographic target: what is the goal of stereotactic
      11-gauge vacuum-assisted breast biopsy?
AB  - OBJECTIVE: This study was undertaken to determine whether complete percutaneous
      excision rather than sampling of the mammographic target conveys any significant
      advantage or disadvantage at stereotactic 11-gauge vacuum-assisted biopsy.
      MATERIALS AND METHODS: A retrospective review was performed of 788 consecutive
      solitary lesions in which the mammographic target was excised (n = 466) or
      sampled (n = 322) at stereotactic 11-gauge vacuum-assisted biopsy. Medical
      records and histologic findings were reviewed to determine the frequency of
      sparing surgery, discordance, histologic underestimation, rebiopsy, complete
      histologic removal of cancer, and complications. Statistical comparisons were
      made using the Fisher's exact test. RESULTS: Complete excision rather than
      sampling of the mammographic target was associated with a significantly lower
      frequency of discordance (1/466, 0.2% vs 8/322, 2.5%; p = 0.004) and a trend
      toward fewer ductal carcinoma in situ underestimates (4/59, 6.8% vs 12/60, 20.0%;
      p = 0.07). Complete histologic removal of cancer was significantly more likely if
      the mammographic target was excised rather than sampled (19/91, 20.9% vs 7/106,
      6.6%; p = 0.006); however, among 91 cancers in which the mammographic target was
      excised, surgery revealed residual cancer in 72 (79.1%). Complete excision rather
      than sampling of the mammographic target yielded no significant differences in
      the frequency of sparing surgery, atypical ductal hyperplasia underestimates,
      rebiopsy, or complications. CONCLUSION: Complete excision rather than sampling of
      the mammographic target was associated with lower frequencies of discordance and
      ductal carcinoma in situ underestimation but had no other advantage or
      disadvantage. Among cancers in which the mammographic target was excised, surgery
      revealed residual cancer in almost 80%.

PMID- 12185045
TI  - Calcifications associated with lactational changes of the breast: mammographic
      findings with histologic correlation.
AB  - OBJECTIVE: We sought to describe the mammographic appearance of calcifications
      associated with histologically confirmed lactational changes of the breast.
      CONCLUSION: Calcifications associated with lactational changes of the breast may
      have a suspicious appearance on mammography. These calcifications may be
      identified on a patient's original screening mammogram or may be a new finding on
      an annual screening examination. Correlating a clinical history of recent
      lactation or a postpartum state is important in establishing a concordance
      between the mammographic and histologic findings. However, despite the benign
      nature of these calcifications, biopsy is recommended because of their suspicious
      morphologic features.

PMID- 12185046
TI  - Hemorrhage into the breast in a restrained driver after a motor vehicle
      collision.

PMID- 12185047
TI  - Revisiting the mammographic follow-up of BI-RADS category 3 lesions.
AB  - OBJECTIVE: Using data collected for one series during 1987-1989 and data
      collected for another series during 1996, we sought to compare the frequency of
      and positive predictive value for carcinoma of the breast in nonpalpable,
      probably benign lesions that had been detected on and followed up with
      mammography. MATERIALS AND METHODS: During 1996, mammography was performed in
      18,435 women of whom 544 (3.0%) had lesions assigned to Breast Imaging Reporting
      and Data System (BI-RADS) category 3 for nonpalpable, probably benign lesions.
      The lesions in the women were assessed as BI-RADS category 3 after the patients
      had undergone a diagnostic study that included additional imaging, sonography,
      and a focused physical examination. Patients with BI-RADS category 3 lesions were
      recommended for mammographic surveillance. A minimum of 2 years of follow-up data
      was available for 511 patients, our study population. We compared the findings
      for our study population with those of the previous study. RESULTS: Ninety-seven
      percent of the follow-up mammograms showed stability or regression of the BI-RADS
      category 3 lesions. Fourteen patients (3%) had nonpalpable interval progression
      revealed on mammography and underwent biopsy. The breast cancer detection rate in
      category 3 lesions among the study population was 0.4% (2/511), which was 14% of
      the patients who had undergone biopsies because of interval progression of the
      lesions. The pathologic stage of the cancers in these two patients was T1b N0.
      CONCLUSION: Compared with the findings from the 1987-1989 study, the frequency of
      BI-RADS category 3 lesions has remained stable; patient compliance for follow-up
      has increased; and the positive predictive value of category 3 lesions for cancer
      has decreased from 1.7% to 0.4% (p = 0.04).

PMID- 12185048
TI  - Breast pseudoaneurysm in a woman after core biopsy: percutaneous treatment with
      alcohol.

PMID- 12185049
TI  - Brachial plexus sonography: a technique for assessing the root level.
AB  - OBJECTIVE: Our study was intended to establish a technique to assess the level of
      the roots of the brachial plexus using high-resolution sonography. MATERIALS AND
      METHODS: The skeleton of a cervical spine was examined in vitro to determine
      whether the vertebrae may be identified individually on sonography by means of
      the evaluation of their transverse processes. Then 20 healthy subjects and five
      patients who had undergone CT of the cervical spine were evaluated
      sonographically, and we attempted to identify the level of individual roots of
      the brachial plexus using the transverse processes as landmarks. To establish the
      reliability of this method, a blinded review of sonograms of the paravertebral
      area obtained at various levels was performed independently by three examiners.
      RESULTS: In vitro, sonography was reliable in depicting the level of the C7
      vertebra because of the absence of the anterior tubercle from its transverse
      processes. In healthy subjects, this feature allowed us to establish the level of
      the roots outside the spine. In our series, the C4-C7 roots were visible
      sonographically in all cases, whereas the C8 and T1 levels were seen,
      respectively, in only 16 of 20 and eight of 20 cases. All examiners correctly
      identified the C7 level in the blinded review of sonograms. CONCLUSION: High
      resolution sonography can reveal the level of the roots of the brachial plexus on
      the basis of the different morphology of the transverse processes of the
      vertebrae. Our study has implications for confirming the exact level of
      pathologic roots before surgery.

PMID- 12185050
TI  - High-resolution sonography of the submandibular space: anatomy and abnormalities.

PMID- 12185051
TI  - Sonography of the painful calf: differential considerations.

PMID- 12185052
TI  - Diagnosis and staging of pancreatic cancer: comparison of mangafodipir trisodium
      enhanced MR imaging and contrast-enhanced helical hydro-CT.
AB  - OBJECTIVE: The purpose of this study was to compare mangafodipir trisodium
      enhanced MR imaging performed with a phased array coil and contrast-enhanced
      single-detector helical CT for accuracy in the detection and local staging of
      pancreatic adenocarcinoma and in the differentiation between cancer and focal
      pancreatitis. SUBJECTS AND METHODS: Forty-two patients with suspected pancreatic
      masses underwent contrast-enhanced helical CT and mangafodipir trisodium-enhanced
      MR imaging at 1.5 T. The images were assessed for the presence or absence of
      tumors; characterization of masses; and presence of vascular invasion, lymph node
      metastases, or liver metastases. Imaging findings were correlated with findings
      at laparotomy, laparoscopy, biopsy, or follow-up. RESULTS: Focal masses were
      present in 36 patients (cancer, n = 26; focal pancreatitis, n = 7; other, n = 3).
      The sensitivity for lesion detection of MR imaging was 100% and of CT, 94%. Two
      small malignant lesions were missed on CT. For the diagnosis of tumor
      nonresectability, the sensitivity of MR imaging and CT was 90% and 80%,
      respectively. Liver metastases were missed on MR imaging in one of the eight
      patients and on CT in four. For differentiation between adenocarcinoma and
      nonadenocarcinoma, the sensitivity of MR imaging was 100% (positive predictive
      value, 90%; negative predictive value, 100%), and the sensitivity of CT was 92%
      (positive predictive value, 80%; negative predictive value, 67%). Receiver
      operating characteristic analysis revealed that the mean area under the curve for
      MR imaging was 0.920 and for CT, 0.832 (not significant). CONCLUSION:
      Mangafodipir trisodium-enhanced MR imaging is as accurate as contrast-enhanced
      helical CT for the detection and staging of pancreatic cancer but offers improved
      detection of small pancreatic metastases and of liver metastases compared with
      CT.

PMID- 12185053
TI  - Helical CT of islet cell tumors of the pancreas: typical and atypical
      manifestations.

PMID- 12185054
TI  - Chronic inflammatory appendiceal conditions that mimic acute appendicitis on
      helical CT.
AB  - OBJECTIVE: Acute appendicitis is commonly diagnosed on CT, but chronic
      appendiceal processes can mimic acute appendicitis. The purpose of this study was
      to identify the frequency of these alternative conditions and their findings on
      helical CT. CONCLUSION: Chronic inflammatory conditions other than acute
      appendicitis were found in 9% of patients who underwent surgery after CT findings
      were interpreted as suspicious for appendicitis. These inflammatory conditions
      were indistinguishable from acute appendicitis when we used either primary or
      secondary CT signs.

PMID- 12185055
TI  - Stomal metastases complicating percutaneous endoscopic gastrostomy: CT findings
      and the argument for radiologic tube placement.
AB  - OBJECTIVE: This article describes the CT appearance of metastatic implantation at
      the percutaneous endoscopic gastrostomy (PEG) tract in patients with malignancy
      of the upper aerodigestive tract. Cumulative data from previous case reports are
      also considered for insight into causes of metastasis and the implications for
      gastrostomy placement in these patients. CONCLUSION: CT showed lobulated soft
      tissue involving the entire abdominal wall PEG tract in all proven cases. CT is
      an effective method for evaluation because the tumor burden lies predominately in
      the abdominal wall and not at the entry or exit site. The stomal implant is often
      the only site of metastatic disease at presentation. In general, CT findings of
      mildly increased soft tissue along the PEG tract are nonspecific, but a lobulated
      mass is highly suspicious for tumor implantation, especially if the one-sided
      thickness exceeds 1 cm. The preponderance of evidence from the existing
      literature points to direct tumor implantation during endoscopic placement as the
      likely cause (rather than hematogenous spread). This conclusion would support the
      alternative of radiologic tube placement in these patients.

PMID- 12185056
TI  - Preoperative detection of hepatocellular carcinoma: ferumoxides-enhanced versus
      mangafodipir trisodium-enhanced MR imaging.
AB  - OBJECTIVE: The purpose of our study was to compare the diagnostic accuracy and
      lesion conspicuity of ferumoxides-enhanced MR imaging with those of mangafodipir
      trisodium-enhanced MR imaging for the preoperative detection of hepatocellular
      carcinoma. SUBJECTS AND METHODS: Twenty-one patients with 39 hepatocellular
      carcinomas underwent ferumoxides-enhanced and mangafodipir trisodium-enhanced MR
      imaging. The diagnosis was established by pathologic examination after surgical
      resection in all patients. Five MR sequences were obtained 30 min after
      ferumoxides administration, and two MR sequences were obtained before and 15 min
      after mangafodipir trisodium administration. Three observers independently
      interpreted both MR images of all sequences on a segment-by-segment basis. The
      diagnostic accuracy of MR imaging was assessed using receiver operating
      characterizing analysis. Lesion (hepatocellular carcinoma > 10 mm in diameter)-to
      liver contrast-to-noise ratio was calculated on MR images. RESULTS: Ferumoxides
      enhanced MR imaging (A(z) = 0.971) was significantly more accurate (p < 0.05)
      than mangafodipir trisodium-enhanced MR imaging (A(z) = 0.950). The mean
      sensitivity of ferumoxides-enhanced MR imaging (86%) was significantly greater (p
      < 0.05) than that of mangafodipir trisodium-enhanced MR imaging (44%) in lesions
      smaller than 10 mm. The mean lesion-to-liver contrast-to-noise ratio of
      hepatocellular carcinoma on ferumoxides-enhanced MR imaging (13.7 +/- 8.8) was
      significantly greater than on mangafodipir trisodium-enhanced MR imaging (5.4 +/-
      5.1) (p < 0.01). CONCLUSION: Ferumoxides-enhanced MR imaging has superior
      diagnostic accuracy in lesions smaller than 10 mm and superior lesion conspicuity
      compared with mangafodipir trisodium-enhanced MR imaging for the preoperative
      detection of hepatocellular carcinoma.

PMID- 12185057
TI  - Hypervascular hepatocellular carcinoma: can double arterial phase imaging with
      multidetector CT improve tumor depiction in the cirrhotic liver?
AB  - OBJECTIVE: We assessed the efficacy of double arterial phase CT with
      multidetector CT for the detection of hypervascular hepatocellular carcinoma in
      the cirrhotic liver. MATERIALS AND METHODS: Double arterial phase images with
      multidetector CT were evaluated using quantitative, qualitative, and receiver
      operating characteristic analyses for 59 patients with 78 hepatocellular
      carcinomas. Early and late arterial phase (double arterial phase) CT scans were
      obtained at a fixed time of 25 and 40 sec, respectively, after administration of
      contrast material. Total dose and injection rate of contrast material were 100 mL
      and 3 mL/sec, respectively. RESULTS: On the basis of the receiver operating
      characteristic curves, the mean area under the curve values of the late (0.98)
      and combined arterial phase CT scans (0.98) were equivalent, and both were
      significantly greater than the mean of the early arterial phase CT scans (0.842)
      for detecting hepatocellular carcinoma (p < 0.05). The mean relative sensitivity
      values obtained with the late (69/78, 88%) and combined arterial phase CT scans
      (70/78, 90%) were also equivalent and were significantly greater than those
      obtained with the early arterial phase CT scans (52/78, 67%; p < 0.001).
      CONCLUSION: Double arterial phase CT with multidetector CT showed no significant
      improvement in effectiveness compared with single late arterial phase CT used
      alone for detecting hypervascular hepatocellular carcinoma in the cirrhotic
      liver.

PMID- 12185058
TI  - Focal nodular hyperplasia inducing hepatic vein obstruction.
AB  - OBJECTIVE: The records of 10 patients with focal nodular hyperplasia inducing
      intrahepatic vein obstruction were reviewed. The purpose of this study was to
      describe and emphasize the imaging features of these findings. CONCLUSION: Focal
      nodular hyperplasia may be responsible for hepatic vein obstruction with hepatic
      vein collaterals. The relatively large size and central location of the lesions
      seem to play important roles in the obstruction of the hepatic veins.

PMID- 12185059
TI  - Virtual cystoscopy of the contrast material-filled bladder in patients with gross
      hematuria.
AB  - OBJECTIVE: The objective of this study was to evaluate the usefulness of virtual
      cystoscopy of the contrast material-filled bladder in evaluating patients with
      gross hematuria. SUBJECTS AND METHODS: Seventy-three consecutive patients who had
      gross hematuria and whose upper urinary tracts had a normal appearance on single
      detector helical CT scans were prospectively evaluated with virtual cystoscopy.
      Source CT data for virtual cystoscopy were obtained on a multidetector CT scanner
      with 1.25-mm slice thickness and transferred to a workstation for interactive
      navigation using volume rendering. Two radiologists independently interpreted the
      virtual cystoscopic images, and discrepancies were resolved by consensus. All
      patients also underwent conventional cystoscopy. We assessed the agreement
      between the findings on virtual and conventional cystoscopy. Using conventional
      cystoscopy as the gold standard, we evaluated the usefulness of virtual
      cystoscopy as an aid in identifying bladder lesions and detecting abnormal
      bladders. RESULTS: Virtual cystoscopy depicted 60 lesions in the bladders of 43
      patients. Fifty-six lesions (in 41 bladders) revealed on virtual cystoscopy were
      true-positive findings. Four lesions in two bladders with abnormal findings were
      false-positive. On virtual cystoscopy, the radiologists missed three lesions in
      two abnormal bladders that were identified on conventional cystoscopy. On virtual
      cystoscopy, 15 (88%) of 17 lesions smaller than 0.5 cm were identified. The
      agreement between the findings of virtual and conventional cystoscopy was
      excellent in the reviewers' identification of bladder lesions (kappa = 0.83) and
      detection of abnormal bladders (kappa = 0.89). The sensitivity and specificity of
      virtual cystoscopy were 95% and 87% for identifying bladder lesions and 95% and
      93% for detecting abnormal bladders. CONCLUSION: Virtual cystoscopy of the
      contrast material-filled bladder is useful for the evaluation of the bladder in
      patients with gross hematuria.

PMID- 12185060
TI  - CT differentiation of large exophytic renal angiomyolipomas and perirenal
      liposarcomas.
AB  - OBJECTIVE: The purpose of our study was to describe the imaging findings and CT
      characteristics that lead to accurate distinction of large exophytic renal
      angiomyolipomas from retroperitoneal perirenal liposarcomas, which at times can
      be confused on imaging studies and even at pathologic examination. MATERIALS AND
      METHODS: We retrospectively analyzed CT images of 15 large exophytic renal
      angiomyolipomas and 12 well-differentiated perirenal liposarcomas. Pathologic
      correlation was available for six of 15 angiomyolipomas and all of the
      liposarcomas. All examinations were evaluated for lesion size, renal parenchymal
      defect, enlarged vessels, kidney displacement, lesion encapsulation or
      margination, associated hemorrhage, and additional angiomyolipomas. The records
      of patients with tuberous sclerosis or the forme fruste of that condition were
      excluded from the study. RESULTS: The average size of the angiomyolipomas was 14
      x 10 cm. They showed a renal parenchymal defect (n = 15), enlarged vessels (n =
      12), renal displacement (n = 14), good margination without a distinct capsule (n
      = 14), hemorrhage (n = 1), and additional (one or two) angiomyolipomas (n = 4).
      The average size of the liposarcomas was 18 x 11.6 cm. They showed enlarged
      vessels (n = 3), renal displacement (n = 11), and encapsulation (n = 4); none
      showed a renal parenchymal defect, hemorrhage, or associated angiomyolipomas.
      CONCLUSION: Although large exophytic angiomyolipomas and well-differentiated
      retroperitoneal liposarcomas may have similar appearances on imaging, careful
      evaluation for a defect in the renal parenchyma combined with the presence of
      enlarged vessels in angiomyolipomas should enable accurate differentiation in
      almost all cases. Achieving an accurate diagnosis can have a significant impact
      on patient treatment.

PMID- 12185062
TI  - Sonographic diagnosis of superior hemispheric testicular infarction.

PMID- 12185063
TI  - Serial isotropic three-dimensional fast FLAIR imaging: using image registration
      and subtraction to reveal active multiple sclerosis lesions.
AB  - OBJECTIVE: Image registration and subtraction to detect the change of disease
      burden in multiple sclerosis on serial MR images should benefit from the use of
      high-resolution isotropic voxels. We compared 1.2-mm isotropic three-dimensional
      (3D) fast fluid-attenuated inversion recovery (FLAIR) images with standard 3-mm
      two-dimensional spin-echo images for the detection of new or enlarging lesions in
      longitudinal studies. SUBJECTS AND METHODS: Serial MR images were obtained at
      baseline, month 6 (n = 20), and month 7 (n = 16). For the half-yearly intervals,
      subtracted 3D FLAIR images and T2-weighted spin-echo images were compared. For
      the monthly intervals, subtracted 3D FLAIR images were compared with triple-dose
      contrast-enhanced T1-weighted spin-echo images. New, enlarging, and enhancing
      lesions were marked in consensus by two radiologists. RESULTS: At the half-yearly
      intervals, 3D FLAIR imaging detected more new or enlarging lesions than T2
      weighted spin-echo imaging, both at the initial interpretation (80 vs 52; p <
      0.001) and after a side-by-side comparison of the lesions (88 vs 65; p < 0.001).
      Post hoc analyses showed the largest benefit for new (rather than enlarging), for
      small, and for temporal lesions. At the monthly intervals, 32 enhancing lesions
      were detected on contrast-enhanced T1-weighted spin-echo images versus 20 new or
      enlarging lesions detected on 3D FLAIR images (p < 0.05). After a side-by-side
      comparison of the lesions, seven additional lesions were identified on 3D FLAIR
      images, making the difference with contrast-enhanced T1-weighted spin-echo images
      insignificant (27 vs 32; p > 0.05). CONCLUSION: Isotropic 3D FLAIR imaging holds
      great promise for the detection of new or enlarging lesions in multiple sclerosis
      using registration and subtraction techniques certainly at longer intervals.

PMID- 12185065
TI  - Bilateral temporal fossa hemangiomas.

PMID- 12185064
TI  - Using relative cerebral blood flow and volume to evaluate the histopathologic
      grade of cerebral gliomas: preliminary results.
AB  - OBJECTIVE: Relative cerebral blood flow has rarely been studied as part of the
      preoperative assessment of tumor grade, although relative cerebral blood volume
      is known to be useful for this assessment. The purpose of our study was to
      determine the usefulness of relative cerebral blood flow in assessing the
      histopathologic grade of cerebral gliomas. SUBJECTS AND METHODS: MR imaging was
      performed in 17 patients with proven cerebral gliomas (11 high-grade gliomas and
      six low-grade gliomas), using a first-pass gadopentetate dimeglumine-enhanced T2
      weighted echoplanar perfusion sequence. The perfusion data were deconvoluted with
      an arterial input function, using singular value decomposition to obtain a color
      map of relative cerebral blood volume and flow; the relative cerebral blood
      volume and flow ratios were expressed relative to values measured in the
      contralateral white matter. The Wilcoxon's rank sum test was performed to test
      the difference between the mean of the relative cerebral blood volume (or flow)
      ratio in high-grade gliomas and that in low-grade gliomas. Receiver operating
      characteristic curve analysis was used to evaluate the association between the
      relative cerebral blood volume (or flow) ratio and the grade of the glioma, as
      well as to calculate the relative cerebral blood volume and flow ratio cutoff
      value permitting discrimination between high- and low-grade gliomas. The
      correlation between relative cerebral blood volume and flow ratios was evaluated
      using Spearman's rank correlation analysis. We also made a qualitative assessment
      regarding the match or mismatch of areas of maximal contrast enhancement with the
      areas of highest color perfusion maps. RESULTS: The mean of the relative cerebral
      blood volume ratio was 4.91 in the high-grade gliomas and 2.00 in the low-grade
      gliomas. The mean relative cerebral blood flow ratio was 4.82 in the high-grade
      gliomas and 1.83 in the low-grade gliomas. A significant difference in each
      relative cerebral blood volume and flow ratio was found between the high- and low
      grade gliomas (Wilcoxon's rank sum test, p < 0.05). Both the relative cerebral
      blood volume and flow ratios strongly matched the grade of the glioma, but the
      difference between the two areas was not significant (receiver operating
      characteristic curve analysis, p > 0.05). The desired cutoff value was 2.93 in
      the relative cerebral blood volume ratio and 3.57 in the relative cerebral blood
      flow ratio. Additionally, there was a strong correlation between the relative
      cerebral blood volume and flow ratios (Spearman's rank correlation coefficient =
      0.762; p < 0.05). There was frequent mismatch (33%) between the qualitative
      assessment of the contrast-enhanced T1-weighted MR images and the perfusion maps.
      CONCLUSION: First-pass gadopentetate dimeglumine-enhanced T2-weighted echoplanar
      perfusion MR imaging is useful for the preoperative assessment of tumor grade. A
      relative cerebral blood flow ratio, in addition to a relative cerebral blood
      volume ratio, can be a useful tool in the evaluation of the histopathologic grade
      of cerebral gliomas.

PMID- 12185066
TI  - Fraction of inspired oxygen in relation to cerebrospinal fluid hyperintensity on
      FLAIR MR imaging of the brain in children and young adults undergoing anesthesia.
AB  - OBJECTIVE: Cerebrospinal fluid (CSF) hyperintensity has been described on fluid
      attenuated inversion recovery (FLAIR) imaging in anesthetized patients who
      underwent MR imaging without apparent subarachnoid abnormality. The purpose of
      our study was to delineate likely causes for this hyperintensity. Specifically,
      we sought to determine whether a high inspired oxygen fraction given as part of
      the anesthetic was responsible for the CSF hyperintensity seen on FLAIR imaging.
      MATERIALS AND METHODS: A retrospective study was conducted using anesthetic
      records and brain MR images of 70 children and young adults who had a FLAIR
      sequence while undergoing general anesthesia. Information about inspired oxygen
      fraction, oxygen saturation, and type of anesthetic agents preceding the FLAIR
      sequence was obtained from the anesthetic record. A pediatric neuroradiologist
      who was unaware of the inspired oxygen fraction and anesthetic agent ascertained
      the presence of CSF hyperintensity in the basilar cisterns and cerebral sulcal
      subarachnoid space. RESULTS: Twenty-one patients received an inspired oxygen
      fraction less than or equal to 0.60, and 49 received an inspired oxygen fraction
      greater than 0.60. Inspired oxygen fraction greater than 0.60 was significantly
      associated with the presence of CSF hyperintensity in the basilar cisterns (p <
      0.001) and in the cerebral sulcal subarachnoid space (p = 0.03). The type of
      anesthetic agent, patient's sex, or status (based on the American Society of
      Anesthesiology physical status and classification system), and presence of
      cardiopulmonary disease or seizure disorder were not associated with CSF
      hyperintensity. CONCLUSION: High inspired oxygen fraction during anesthesia is
      associated with CSF hyperintensity in the basilar cisterns and the cerebral
      sulcal subarachnoid space on FLAIR imaging in children and young adults.
      Physicians should be aware of this finding to avoid misinterpreting this artifact
      as an abnormality.

PMID- 12185067
TI  - Synovial sarcoma in pediatric patients.

PMID- 12185072
TI  - Phosphorylation and mutations of Ser(16) in human phenylalanine hydroxylase.
      Kinetic and structural effects.
AB  - Phosphorylation of phenylalanine hydroxylase (PAH) at Ser(16) by cyclic AMP
      dependent protein kinase is a post-translational modification that increases its
      basal activity and facilitates its activation by the substrate l-Phe. So far
      there is no structural information on the flexible N-terminal tail (residues 1
      18), including the phosphorylation site. To get further insight into the
      molecular basis for the effects of phosphorylation on the catalytic efficiency
      and enzyme stability, molecular modeling was performed using the crystal
      structure of the recombinant rat enzyme. The most probable conformation and
      orientation of the N-terminal tail thus obtained indicates that phosphorylation
      of Ser(16) induces a local conformational change as a result of an electrostatic
      interaction between the phosphate group and Arg(13) as well as a repulsion by
      Glu(280) in the loop at the entrance of the active site crevice structure. The
      modeled reorientation of the N-terminal tail residues (Met(1)-Leu(15)) on
      phosphorylation is in agreement with the observed conformational change and
      increased accessibility of the substrate to the active site, as indicated by
      circular dichroism spectroscopy and the enzyme kinetic data for the full-length
      phosphorylated and nonphosphorylated human PAH. To further validate the model we
      have prepared and characterized mutants substituting Ser(16) with a negatively
      charged residue and found that S16E largely mimics the effects of phosphorylation
      of human PAH. Both the phosphorylated enzyme and the mutants with acidic side
      chains instead of Ser(16) revealed an increased resistance toward limited tryptic
      proteolysis and, as indicated by circular dichroism spectroscopy, an increased
      content of alpha-helical structure. In agreement with the modeled structure, the
      formation of an Arg(13) to Ser(16) phosphate salt bridge and the conformational
      change of the N-terminal tail also explain the higher stability toward limited
      tryptic proteolysis of the phosphorylated enzyme. The results obtained with the
      mutant R13A and E381A further support the model proposed for the molecular
      mechanism for the activation of the enzyme by phosphorylation.

PMID- 12185073
TI  - A RANK/TRAF6-dependent signal transduction pathway is essential for osteoclast
      cytoskeletal organization and resorptive function.
AB  - Signaling through receptor activator of nuclear factor-kappaB (RANK) is essential
      for the differentiation and activation of osteoclasts, the cell principally
      responsible for bone resorption. Animals genetically deficient in RANK or the
      cognate RANK ligand are profoundly osteopetrotic because of the lack of bone
      resorption and remodeling. RANK provokes biochemical signaling via the
      recruitment of intracellular tumor necrosis factor receptor-associated factors
      (TRAFs) after ligand binding and receptor oligomerization. To understand the RANK
      mediated signal transduction mechanism in osteoclastogenesis, we have designed a
      system to recapitulate osteoclast differentiation and activation in vitro by
      transfer of the RANK cDNA into hematopoietic precursors genetically deficient in
      RANK. Gene transfer of RANK constructs that are selectively incapable of binding
      different TRAF proteins revealed that TRAF pathways downstream of RANK that
      affect osteoclast differentiation are functionally redundant. In contrast, the
      interaction of RANK with TRAF6 is absolutely required for the proper formation of
      cytoskeletal structures and functional resorptive activity of osteoclasts.
      Moreover, signaling via the interleukin-1 receptor, which also utilizes TRAF6,
      rescues the osteoclast activation defects observed in the absence of RANK/TRAF6
      interactions. These studies are the first to define the functional domains of the
      RANK cytoplasmic tail that control specific differentiation and activation
      pathways in osteoclasts.

PMID- 12185074
TI  - A comparative study on the hydroperoxide and thiol specificity of the glutathione
      peroxidase family and selenoprotein P.
AB  - Glutathione peroxidase catalyzes the reduction of hydrogen peroxide and organic
      hydroperoxide by glutathione and functions in the protection of cells against
      oxidative damage. Glutathione peroxidase exists in several forms that differ in
      their primary structure and localization. We have also shown that selenoprotein P
      exhibits a glutathione peroxidase-like activity (Saito, Y., Hayashi, T., Tanaka,
      A., Watanabe, Y., Suzuki, M., Saito, E., and Takahashi, K. (1999) J. Biol. Chem.
      274, 2866-2871). To understand the physiological significance of the diversity
      among these enzymes, a comparative study on the peroxide substrate specificity of
      three types of ubiquitous glutathione peroxidase (cellular glutathione
      peroxidase, phospholipid hydroperoxide glutathione peroxidase, and extracellular
      glutathione peroxidase) and of selenoprotein P purified from human origins was
      done. The specific activities and kinetic parameters against two hydroperoxides
      (hydrogen peroxide and phosphatidylcholine hydroperoxide) were determined. We
      next examined the thiol specificity and found that thioredoxin is the preferred
      electron donor for selenoprotein P. These four enzymes exhibit different peroxide
      and thiol specificities and collaborate to protect biological molecules from
      oxidative stress both inside and outside the cells.

PMID- 12185075
TI  - Mutations in the extracellular amino-terminal domain of the NK2 neurokinin
      receptor abolish cAMP signaling but preserve intracellular calcium responses.
AB  - By combining real time measurements of agonist binding, by fluorescence resonance
      energy transfer, and of subsequent responses, we proposed previously that the
      neurokinin NK2 receptor preexists in equilibrium between three states: inactive,
      calcium-triggering, and cAMP-producing. Thr(24) and Phe(26) of the NK2 receptor
      extracellular domain are considered to interact with neuropeptide agonists based
      on the reduction of affinity when they are substituted by alanine. Using
      fluorescence resonance energy transfer, we now quantify the binding kinetics of
      two Texas Red-modified neurokinin A agonists to the fluorescent wild-type (Y
      NK2wt) and the mutant (Y-NK2mut) receptor carrying Thr(24) --> Ala and Phe(26) -
      > Ala mutations. TR1-neurokinin A binds with a fast component and a slow
      component to the Y-NK2wt receptor and triggers both a calcium and a cAMP
      response. In contrast, on the mutant receptor, it binds in a single fast step
      with a lower apparent affinity and activates only the calcium response. Another
      agonist, TRC4-neurokinin A, binds to both wild-type and mutant receptors in a
      single fast step, with similar affinities and kinetics and promotes only calcium
      signaling. Kinetic modeling of ligand binding and receptor interconversions is
      carried out to analyze phenotypic changes in terms of binding alterations or
      changes in the transitions between conformational states. We show that the
      binding and response properties of the Y-NK2mut receptor are best described
      according to a phenotype where a reduction of the transition between the inactive
      and the active states occurs.

PMID- 12185076
TI  - Characterization and expression of mammalian cyclin b3, a prepachytene meiotic
      cyclin.
AB  - We report the identification and expression pattern of a full-length human cDNA
      and a partial mouse cDNA encoding cyclin B3. Cyclin B3 (CCNB3) is conserved from
      Caenorhabditis elegans to Homo sapiens and has an undefined meiotic function in
      female, but not male Drosophila melanogaster. We show that H. sapiens cyclin B3
      interacts with cdk2, is localized to the nucleus, and is degraded during anaphase
      entry after the degradation of cyclin B1. Degradation is dependent on sequences
      conserved in a destruction box motif. Overexpression of nondegradable cyclin B3
      blocks the mitotic cell cycle in late anaphase, and at higher doses it can
      interfere with progression through G(1) and entry into S phase. H. sapiens cyclin
      B3 mRNA and protein are detected readily in developing germ cells in the human
      testis and not in any other tissue. The mouse cDNA has allowed us to further
      localize cyclin B3 mRNA to leptotene and zygotene spermatocytes. The expression
      pattern of mammalian cyclin B3 suggests that it may be important for events
      occurring in early meiotic prophase I.

PMID- 12185077
TI  - S9, a 19 S proteasome subunit interacting with ubiquitinated NF-kappaB2/p100.
AB  - Proteasome-mediated processing of the nfkappab2 gene product p100 is a regulated
      event that generates the NF-kappaB subunit p52. This event can be induced through
      p100 phosphorylation by a signaling pathway involving the nuclear factor-kappaB
      inducing kinase (NIK). The C-terminal region of p100, which contains its
      phosphorylation site and a death domain, plays a pivotal role in regulating the
      processing of p100. To understand the biochemical mechanism of p100 processing,
      we searched for cellular factors interacting with the C-terminal regulatory
      region of p100 using the yeast two-hybrid system. This led to the identification
      of S9, a non-ATPase subunit of the 19 S proteasome with no known functions.
      Interestingly, the S9/p100 interaction could be induced by NIK but not by a
      catalytically inactive NIK mutant. This inducible molecular interaction required
      p100 ubiquitination and was dependent on the intact death domain. We further
      demonstrated that the death domain is essential for NIK-induced post
      translational processing of p100, thus providing a functional link between the S9
      binding and the processing of p100. Finally, we provide genetic evidence for the
      essential role of S9 in the inducible processing of p100.

PMID- 12185078
TI  - A new easter-type serine protease cleaves a masquerade-like protein during
      prophenoloxidase activation in Holotrichia diomphalia larvae.
AB  - The prophenoloxidase (proPO) activation pathway, like the vertebrate complement
      system, consists of a protease cascade and functions as a non-self-recognition
      system in these animals. Determining the molecular mechanism by which pattern
      recognition molecules differentiate non-self from self and transduce signals that
      stimulate defense responses is a key for understanding the ways in which innate
      immune systems are regulated. However, the proPO system is poorly defined at the
      molecular level. The proPO-activating system of the insect Holotrichia diomphalia
      comprises several components, some of which have been cloned and characterized,
      such as the novel 27-kDa proPO-activating factor-III (PPAF-III) from the plasma
      of H. diomphalia larvae and two prophenoloxidases. The PPAF-III gene encodes an
      easter-type serine protease zymogen consisting of 351 amino acid residues with a
      mass of 40 kDa. The purified 27-kDa PPAF-III specifically cleaved a 55-kDa
      proPPAF-II to generate a 45-kDa PPAF-II with or without Ca2+ present.
      Furthermore, two Holotrichia prophenoloxidases (proPO-I and -II) have been
      characterized, and their structural changes during activation were examined by in
      vitro reconstitution experiments. When the proPOs were incubated with PPAF-I, the
      79-kDa proPOs were converted to 76-kDa proPOs, which did not exhibit any
      phenoloxidase (PO) activity. However, when the proPOs were incubated
      simultaneously with PPAF-I, proPPAF-II, and PPAF-III in the presence of Ca2+, a
      60-kDa protein (PO-1) with PO activity was detected in addition to the 76-kDa
      proPO-II protein. These results indicate that the conversion of Holotrichia
      proPOs to enzymatically active phenoloxidase is accomplished by PPAF-I, PAF-II,
      and PPAF-III through a two-step limited proteolysis in the presence of Ca2+.

PMID- 12185079
TI  - Protein phosphatase-1 dephosphorylates the C-terminal domain of RNA polymerase
      II.
AB  - Transcription by RNA polymerase-II (RNAPII) is controlled by multisite
      phosphorylation of the heptapeptide repeats in the C-terminal domain (CTD) of the
      largest subunit. Phosphorylation of CTD is mediated by the cyclin-dependent
      protein kinases Cdk7 and Cdk9, whereas protein serine/threonine phosphatase FCP1
      dephosphorylates CTD. We have recently reported that human immunodeficiency virus
      1 (HIV-1) transcription is positively regulated by protein phosphatase-1 (PP1)
      and that PP1 dephosphorylates recombinant CTD. Here, we provide further evidence
      that PP1 can dephosphorylate RNAPII CTD. In vitro, PP1 dephosphorylated
      recombinant CTD as well as purified RNAPII CTD. HeLa nuclear extracts were found
      to contain a species of PP1 that dephosphorylates both serine 2 and serine 5 of
      the heptapeptide repeats. In nuclear extracts, PP1 and FCP1 contributed roughly
      equally to the dephosphorylation of serine 2. PP1 co-purified with RNAPII by gel
      filtration and associated with RNAPII on immunoaffinity columns prepared with
      anti-CTD antibodies. In cultured cells treated with CTD kinase inhibitors, the
      dephosphorylation of RNAPII on serine 2 was inhibited by 45% by preincubation
      with okadaic acid, which inhibits phosphatases of PPP family, including PP1 but
      not FCP1. Our data demonstrate that RNAPII CTD is dephosphorylated by PP1 in
      vitro and by PPP-type phosphatase, distinct from FCP1, in vivo.

PMID- 12185080
TI  - Decreased endothelial nitric-oxide synthase (eNOS) activity resulting from
      abnormal interaction between eNOS and its regulatory proteins in hypoxia-induced
      pulmonary hypertension.
AB  - In the pulmonary artery isolated from 1-week hypoxia-induced pulmonary
      hypertensive rats, endothelial NO production stimulated by carbachol was
      decreased significantly in in situ visualization using diaminofluorescein-2
      diacetate and also in cGMP content. This change was followed by the decrease in
      carbachol-induced endothelium-dependent relaxation. Protein expression of
      endothelial NO synthase (eNOS) and its regulatory proteins, caveolin-1 and heat
      shock protein 90, did not change in the hypoxic pulmonary artery, indicating that
      chronic hypoxia impairs eNOS activity at posttranslational level. In the hypoxic
      pulmonary artery, the increase in intracellular Ca(2+) level stimulated by
      carbachol but not by ionomycin was reduced. We next focused on changes in Ca(2+)
      sensitivity of the eNOS activation system. A morphological study revealed atrophy
      of endothelial cells and a peripheral condensation of eNOS in hypoxic endothelial
      cells preserving co-localization between eNOS and Golgi or plasma membranes.
      However, eNOS was tightly coupled with caveolin-1, and was dissociated from heat
      shock protein 90 or calmodulin in the hypoxic pulmonary artery in either the
      presence or absence of carbachol. Furthermore, eNOS Ser(1177) phosphorylation in
      both conditions significantly decreased without affecting Akt phosphorylation in
      the hypoxic artery. In conclusion, chronic hypoxia impairs endothelial Ca(2+)
      metabolism and normal coupling between eNOS and caveolin-1 resulted in eNOS
      inactivity.

PMID- 12185081
TI  - Regulation of caveolin-1 expression and secretion by a protein kinase cepsilon
      signaling pathway in human prostate cancer cells.
AB  - Caveolin-1, androgen receptor, c-Myc, and protein kinase Cepsilon (PKCepsilon)
      proteins are overrepresented in most advanced prostate cancer tumors. Previously,
      we demonstrated that PKCepsilon has the capacity to enhance the expression of
      both caveolin-1 and c-Myc in cultured prostate cancer cells and is sufficient to
      induce the growth of androgen-independent tumors. In this study, we have
      uncovered further evidence of a functional interplay among these proteins in the
      CWR22 model of human prostate cancer. The results demonstrated that PKCepsilon
      expression was naturally up-regulated in recurrent CWR22 tumors and that this
      oncoprotein was required to sustain the androgen-independent proliferation of CWR
      R1 cells in culture. Gene transfer experiments demonstrated that PKCepsilon had
      the potential to augment the expression and secretion of a biologically active
      caveolin-1 protein that supports the growth of the CWR-R1 cell line. Antisense
      and pharmacological experiments provided additional evidence that the sequential
      activation of PKCepsilon, mitogen-activated protein kinases, c-Myc, and androgen
      receptor signaling drove the downstream expression of caveolin-1 in CWR-R1 cells.
      Finally, we demonstrate that mitogen-activated protein kinases were required
      downstream of PKCepsilon to derepress the transcriptional elongation of the c-myc
      gene. Our findings support the hypothesis that PKCepsilon may advance the
      recurrence of human prostate cancer by promoting the expression of several
      important downstream effectors of disease progression.

PMID- 12185082
TI  - Cathepsin B mediates tumor necrosis factor-induced arachidonic acid release in
      tumor cells.
AB  - Arachidonic acid (AA) generated by cytosolic phospholipase A2 (cPLA2) has been
      suggested to function as a second messenger in tumor necrosis factor (TNF)
      induced death signaling. Here, we show that cathepsin B-like proteases are
      required for the TNF-induced AA release in transformed cells. Pharmaceutical
      inhibitors of cathepsin B blocked TNF-induced AA release in human breast (MCF
      7S1) and cervix (ME-180as) carcinoma as well as murine fibrosarcoma (WEHI-S)
      cells. Furthermore, TNF-induced AA release was significantly reduced in cathepsin
      B-deficient immortalized murine embryonic fibroblasts. Employing cPLA2-deficient
      MCF-7S1 cells expressing ectopic cPLA2 or cPLA2-deficient immortalized murine
      embryonic fibroblasts, we showed that cPLA2 is dispensable for TNF-induced AA
      release and death in these cells. Furthermore, TNF-induced cathepsin B-dependent
      AA release could be dissociated from the cathepsin B-independent cell death in
      MCF-7S1 cells, whereas both events required cathepsin B activity in other cell
      lines tested. These data suggest that cathepsin B inhibitors may prove useful not
      only in the direct control of cell death but also in limiting the damage
      associated inflammation.

PMID- 12185083
TI  - Lobe-dependent regulation of ryanodine receptor type 1 by calmodulin.
AB  - Calmodulin activates the skeletal muscle Ca(2+) release channel RYR1 at nm Ca(2+)
      concentrations and inhibits the channel at microm Ca(2+) concentrations. Using a
      deletion mutant of calmodulin, we demonstrate that amino acids 2-8 are required
      for high affinity binding of calmodulin to RYR1 at both nm and microm Ca(2+)
      concentrations and are required for maximum inhibition of the channel at microm
      Ca(2+) concentrations. In contrast, the addition of three amino acids to the N
      terminus of calmodulin increased the affinity for RYR1 at both nm and microm
      Ca(2+) concentrations, but destroyed its functional effects on RYR1 at nm Ca(2+).
      Using both full-length RYR1 and synthetic peptides, we demonstrate that the
      calmodulin-binding site on RYR1 is likely to be noncontiguous, with the C
      terminal lobe of both apocalmodulin and Ca(2+)-calmodulin binding to amino acids
      between positions 3614 and 3643 and the N-terminal lobe binding at sites that are
      not proximal in the primary sequence. Ca(2+) binding to the C-terminal lobe of
      calmodulin converted it from an activator to an inhibitor, but an interaction
      with the N-terminal lobe was required for a maximum effect on RYR1. This
      interaction apparently depends on the native sequence or structure of the first
      few amino acids at the N terminus of calmodulin.

PMID- 12185084
TI  - PH-induced collapse of the extracellular loops closes Escherichia coli maltoporin
      and allows the study of asymmetric sugar binding.
AB  - LamB (maltoporin) is essential for the uptake of maltose and malto
      oligosaccharides across the outer membrane of Escherichia coli. Purified LamB was
      reconstituted in artificial lipid bilayer membranes forming channels in the
      permanently open configuration at neutral pH. Almost complete channel closure was
      observed when the pH on both sides of the membrane was lowered to pH 4. When LamB
      was added to only one side of the membrane, the cis-side, and the pH was lowered
      at either side of the membrane, the cis- or the trans-side, the response to pH
      was asymmetric, suggesting preferential orientation of maltoporin channels and pH
      dependent closure of only one side of the channel. In experiments with LamB
      mutants in which major external loops L4, L6, and/or L9 were deleted, we
      identified the surface-exposed loops L4 and L6 as the cause of pH-mediated
      closure. The pH dependence of the LamB channel is consistent with the assumption
      that it inserts in a preferential orientation into the lipid bilayer. About 70
      80% of the reconstituted channels are oriented with the extracellular entrance
      toward the side to which the protein was added (the cis-side) and with the
      periplasmic opening on the opposite side (the trans-side). The possibility of
      closing the channels, which are oriented in the reverse direction by low pH at
      the trans-side, allowed the deduction of channel asymmetry with respect to
      carbohydrate binding kinetics. Whereas maltose binding was found to be almost
      symmetric with respect to the channel orientation, the sucrose and trehalose
      binding to LamB was asymmetric. The results are discussed in respect to possible
      physiological function of the pH-dependent closure of maltoporin.

PMID- 12185085
TI  - Two nonadjacent regions in enteroaggregative Escherichia coli flagellin are
      required for activation of toll-like receptor 5.
AB  - Flagellin is the major structural protein of the flagella of Gram-negative
      bacteria. Recent work has demonstrated that flagellin is a potent trigger of
      innate immune responses in a number of eukaryotic cells and organisms, including
      both mammals and plants. In several different human epithelial cell lines, this
      innate immune response involves toll-like receptor 5 (TLR5). The mechanisms by
      which flagellin activates TLR5 and the importance of this interaction in other
      model systems of flagellin-induced inflammation remain unknown. In this work,
      random and site-directed mutagenesis of the inflammatory flagellin from
      enteroaggregative Escherichia coli identified two regions in the conserved D1
      domain that are required for interleukin-8 release and TLR5 activation. In
      contrast, large regions of the variable domain could be excised without reducing
      the inflammatory activity. In addition, regions of the protein analogous to
      epitopes that trigger innate immune responses in plants are not involved in Caco
      2 flagellin responses. These results highlight the complexity of the interaction
      between bacterial flagellin and its eukaryotic recognition partners and provide
      the basis for further studies to characterize the innate immune response to
      flagellin.

PMID- 12185086
TI  - Protein phosphatase 2A regulates binding of Cdc45 to the prereplication complex.
AB  - In eukaryotic cells, an ordered sequence of events leads to the initiation of DNA
      replication. During the G(1) phase of the cell cycle, a prereplication complex
      (pre-RC) consisting of ORC, Cdc6, Cdt1, and MCM2-7 is established at replication
      origins on the chromatin. At the G(1)/S transition, MCM10 and the protein kinases
      Cdc7-Dbf4 and Cdk2-cyclin E cooperate to recruit Cdc45 to the pre-RC, followed by
      origin unwinding, RPA binding, and recruitment of DNA polymerases. Using the
      soluble DNA replication system derived from Xenopus eggs, we demonstrate that
      immunodepletion of protein phosphatase 2A (PP2A) from egg extracts and inhibition
      of PP2A activity by okadaic acid abolish loading of Cdc45 to the pre-RC.
      Consistent with a defect in Cdc45 loading, origin unwinding and the loading of
      RPA and DNA polymerase alpha are also inhibited. Inhibition of PP2A has no effect
      on MCM10 loading and on Cdc7-Dbf4 or Cdk2 activity. The substrate of PP2A is
      neither a component of the pre-RC nor Cdc45. Instead, our data suggest that PP2A
      functions by dephosphorylating and activating a soluble factor that is required
      to recruit Cdc45 to the pre-RC. Furthermore, PP2A appears to counteract an
      unknown inhibitory kinase that phosphorylates and inactivates the same factor.
      Thus, the initiation of eukaryotic DNA replication is regulated at the level of
      Cdc45 loading by a combination of stimulatory and inhibitory phosphorylation
      events.

PMID- 12185087
TI  - Host defense proteins of the male reproductive tract.

PMID- 12185088
TI  - Androgen-binding protein and reproduction: where do we stand?

PMID- 12185089
TI  - Building public trust in research.

PMID- 12185090
TI  - A brief review of current and proposed federal government regulation of assisted
      reproduction laboratories in the United States.

PMID- 12185091
TI  - McLachlan et al (2002) point out the fact that mammalian spermatogenesis requires
      an intratesticular testosterone concentration many times higher than normal serum
      levels.

PMID- 12185095
TI  - Deleted in azoospermia associated protein 1 shuttles between nucleus and
      cytoplasm during normal germ cell maturation.
AB  - DAZAP1 (Deleted in Azoospermia Associated Protein 1) was originally identified
      through its interaction with a putative male azoospermia factor, DAZ (Deleted in
      Azoospermia). It contains 2 RNA-binding domains (RBDs) and a proline-rich C
      terminal portion and is expressed most abundantly in testes. We used RNA in situ
      hybridization and immunocytochemistry to study the expression of Dazap1 in mouse
      testes. Dazap1 messenger RNA (mRNA) was present predominantly in immature germ
      cells, between the intermediate spermatogonia and preleptotene spermatocyte
      stages. The DAZAP1 protein was more abundant in germ cells of later stages of
      development and showed a dynamic subcellular distribution. High expression of
      DAZAP1 was first detected in midpachytene spermatocytes in stage VII tubules. In
      these cells, DAZAP1 was present in both the cytoplasm and the nuclei and was
      clearly excluded from the sex vesicles. In round spermatids, DAZAP1 was localized
      mainly in the nuclei, whereas in elongated spermatids, it redistributed to the
      cytoplasm. The subcellular distribution of DAZAP1 suggests that it shuttles
      between the nucleus and the cytoplasm and may play a role in mRNA transport
      and/or localization.

PMID- 12185096
TI  - Optimal power transformations for analysis of sperm concentration and other semen
      variables.
AB  - The nongaussian (or nonnormal) distribution of sperm concentration, and variables
      deriving from it, is a common practical problem in the statistical evaluation of
      semen data. Yet it has been little studied, and its importance to data analysis,
      as well as to practical remedies, is not widely appreciated. Inappropriate use of
      the raw scale of measurement produces inflated estimates of mean and variance,
      leading to false-negative (underpowered) statistical comparisons and excessive
      sample size estimates. This study employs the Box-Cox family of power transforms
      to illustrate by a simple graphical method how to identify optimal power
      transforms for semen data variables. Using robust statistical methods, it is
      shown that the nongaussian distribution is due to right skewing rather than
      multimodality or influential outliers. The optimal power transform, typically in
      the region of 0.15 to 0.35 (most easily implemented as a cube-root
      transformation), usually performs better than the logarithmic transformation in
      normalizing the data. In addition, the power transformation has an important
      practical advantage over the logarithmic transformation in the appropriate
      handling of zeros (azoospermia), a regular and important features of such data
      sets in practice.

PMID- 12185097
TI  - Development of an in vivo model to study testicular morphogenesis.
AB  - We have developed an in vivo model to examine testicular cord formation by
      isolated Sertoli and myoid cells when implanted under the kidney capsule of
      severe combined immunodeficient (SCID) mice. Neonatal porcine Sertoli (92.5% +/-
      3.5%) and myoid (2.2% +/- 0.7%) cellular aggregates were transplanted underneath
      the kidney capsule of SCID mice. Grafts were removed between 0 and 60 days
      posttransplantation and examined histologically for the progressive development
      of structures resembling testicular cords. Aggregates began to reorganize by day
      3, and cord structures were present at day 7 posttransplantation. These
      structures became larger and more defined as the time progressed after
      implantation. To localize Sertoli and peritubular myoid cells, grafts were
      immunostained for the Sertoli cell proteins, vimentin, DNA transcription factor
      GATA-4, and Mullerian inhibiting substance (MIS), as well as for a myoid cell
      protein, smooth muscle alpha-actin. In the "seminiferous" epithelial layer, the
      Sertoli cells were arranged with their nuclei along the basal edge adjacent to
      the peritubular myoid cells that were surrounding the tubules. Moreover, the
      expression of MIS mimicked that during porcine testicular development, suggesting
      the Sertoli cells were developing normally. In addition, proliferating cell
      nuclear antigen (PCNA) was detected in the Sertoli cells at all time points,
      indicating the proliferation of Sertoli cells in the grafts, which is consistent
      with Sertoli cell proliferation prior to puberty in the native porcine testis.
      These results suggest that the specific factors required for cord formation and
      prepubertal development are inherent in the transplanted cells. Moreover, we have
      developed a novel in vivo transplantation model to study seminiferous cord
      formation and prepubertal development.

PMID- 12185098
TI  - Examination of the binding ability of bovine spermatozoa to the zona pellucida as
      an indicator of fertility.
AB  - Despite the development of many new techniques, laboratory assays still do not
      predict male fertility accurately. To identify targets for laboratory assessment,
      we first need to determine which steps in fertilization are most often defective
      in subfertile males. We developed a competitive in vitro fertilization assay in
      which spermatozoa from 2 different males, stained with different lipophilic dyes,
      are incubated together with oocytes in a droplet. By exposing mixed spermatozoa
      to the same oocytes, this assay controls for many of the variables of in vitro
      fertilization and should allow identification of the most common faulty steps in
      fertilization. The relationship of zona-binding ability to fertility is
      controversial. Therefore, as a first step, we determined if zona pellucida
      binding ability, measured by this competitive assay, was related to bovine
      spermatozoal fertility. Fertility data were collected from 2 groups of bulls by 2
      means of evaluation, nonreturn to estrus rates postinsemination and competitive
      insemination. In the nonreturn to estrus study, semen samples from 15 bulls were
      effectively ranked by zona-binding ability, using pairwise competitive in vitro
      zona-binding assays (R(2) = 0.84). However, this ranking was not significantly
      correlated with nonreturn rates (r = -0.04). In the competitive insemination
      study, semen samples from 8 bulls were effectively ranked by pairwise comparison
      using the competitive zona-binding assay (R(2) = 0.67). Again, this ranking was
      not significantly correlated to the competitive insemination index calculated for
      these bulls (r = 0.29). In the third study, we tested 3 bulls to determine if in
      vivo zona binding, assessed by the number of accessory spermatozoa, was
      correlated with in vitro zona binding. The number of accessory spermatozoa on
      oocytes recovered from cows after mating was not correlated with in vitro
      competitive binding of the spermatozoa. In conclusion, in vitro competitive zona
      binding was not correlated with bovine fertility or binding of accessory
      spermatozoa to oocytes in vivo.

PMID- 12185099
TI  - Prostate epithelial expression of a novel androgen target gene.
AB  - To better understand the role of androgens in prostate development and disease it
      is important to characterize androgen-regulated genes in the prostate. Using
      suppression subtractive hybridization between congenitally androgen-deficient
      (hpg) and androgen-replaced hpg mouse prostates, we have cloned a novel androgen
      up-regulated gene from mouse prostate (AUMP). The messenger RNA sequence of AUMP
      consists of 805 nucleotides with an open reading frame of 408 base pairs. In non
      hpg mice with normal androgen levels, AUMP is selectively expressed in the
      prostate, as shown by reverse transcriptase-polymerase chain reaction and
      Northern blot analysis of 9 organs. Depletion of androgens via castration of
      mature mice resulted in loss of AUMP expression, whereas testosterone replacement
      restored it. Tissue in situ hybridization localized AUMP expression to the
      luminal epithelial cells of the androgen-sufficient prostate. Database searches
      indicate that AUMP codes for a novel protein that shares approximately 65%
      similarity and 35% identity to palmitoyl protein thioesterase of human, rat,
      mouse, and bovine. A motif for protein-transport protein, which promotes
      translocation as well as integration of secretory proteins into membrane, is also
      present. Further efforts will be made to obtain the human homologue of AUMP that
      will enable evaluation of its role in normal and diseased human prostate.

PMID- 12185101
TI  - Antisperm autoantibody response after unilateral vas deferens ligation in rats:
      when does it develop?
AB  - Unilateral obstruction or injury to the vas deferens can result in significant
      injury to the contralateral testicle. Antisperm autoantibodies are thought to
      play a significant role in this phenomenon. It has been reported that early
      surgical repair of the vas, before the development of antisperm autoantibodies,
      will prevent any potential damage to the contralateral testicle. This led us to
      investigate the timing of the antisperm antibody production and to attempt to
      determine whether antibody production precedes histologic testicular damage in
      the Lewis rat model. In a controlled study, mature rats were divided into
      temporal groups, with the experimental animals all receiving a unilateral
      vasectomy. At postoperative endpoints of 1, 7, 15, or 30 days, blood samples were
      collected for immunologic assay, and the testicles were harvested for histologic
      examination. Antibody levels were measured by an immunobead test using goat anti
      rat immunoglobulin G (IgG)-coated Sepharose beads; tissue sections were fixed in
      Bouin solution, embedded in paraffin, and stained with hematoxylin and eosin.
      There was no statistically significant histologic difference between any of the
      groups. However, immunologic evaluation revealed a statistically significant
      increase in immunobead antibody binding in the 30-day group compared to the
      control groups (P = .02). These data seem to indicate that in this model,
      antisperm antibody production is not evident until 15-30 days after unilateral
      injury to the vas deferens occurs, and the development of these antibodies
      precedes any demonstrable histologic damage to the testicle. If it is correct to
      infer that human antisperm antibody production will also precede histologic
      testicular damage, and further, that the onset of the human autoantibody response
      may vary from several days to weeks, then in cases of suspected or known ductal
      injury, the clinical monitoring of antisperm antibody levels could enable
      testicular damage to be predicted prior to its development and thus be avoided.

PMID- 12185100
TI  - Puberty is delayed in male growth hormone receptor gene-disrupted mice.
AB  - The role of insulin-like growth factor-I (IGF-I) in the initiation of puberty and
      testicular function is poorly understood. Growth hormone (GH) receptor (R) gene
      disrupted mice or GHR gene "knockouts" (GHR-KO) are GH resistant and IGF-I
      deficient. To assess whether the age of sexual maturation is affected by the
      absence of IGF-I, various parameters of sexual development including testicular
      and accessory reproductive organ weights, balanopreputial separation, germ cell
      development, and intratesticular testosterone levels were determined in normal
      and GHR-KO mice between the ages of 25 and 60 days. In addition, at 36 days of
      age, the testosterone response to luteinizing hormone (LH) treatment was assessed
      in these mice. The results indicate that the balanopreputial separation was
      delayed 5 days, and a significant increase in the weights of the seminal vesicles
      (SV) occurred later in GHR-KO mice than in normal animals (between 30 and 35 days
      and between 35 and 40 days, respectively). Also, the weights of testes and
      epididymii were significantly reduced in GHR-KO mice. The intratesticular
      testosterone levels and the testosterone response to LH treatment were attenuated
      in GHR gene-disrupted mice. Furthermore, elongated spermatids appeared later in
      the testes of GHR-KO mice than in the testes of normal mice. These results
      suggest that the absence of IGF-I secretion delays the normal course of sexual
      maturation in male GHR-KO mice, indicating that IGF-I plays an important role in
      the initiation of puberty in male mice.

PMID- 12185102
TI  - Localization and physiological implication of aldose reductase and sorbitol
      dehydrogenase in reproductive tracts and spermatozoa of male rats.
AB  - The polyol metabolizing pathway, which consists of two enzymes, aldose reductase
      (AR) and sorbitol dehydrogenase (SDH), converts glucose to fructose. The
      enzymatic activities, expression, and localization of AR and SDH were studied in
      reproductive tracts and spermatozoa of male rats by immunohistochemistry, Western
      blotting, and enzyme assays. Immunoreactivity to an AR antibody was observed
      mainly in epithelia of epididymis, seminal vesicle, vas deferens, and prostate
      gland in adult rats. Similar staining profiles were observed for these tissues
      when an SDH antibody was used. However, in testis, the cells that express these 2
      enzymes differed; whereas AR was expressed in Sertoli cells and to lesser extent
      in spermatogenic cells, SDH was detected in spermatogenic cells of seminiferous
      tubules. This cell type-specific gene expression was confirmed in primary
      cultured cells isolated from rat testes. SDH protein levels were higher during
      spermatid elongation, and large amounts of SDH were carried over to the
      spermatozoa. Because one of the functions of members of the aldo-keto reductase
      superfamily is to detoxify harmful carbonyl compounds, an intrinsic function of
      AR in Sertoli cells may be to catalyze the reduction of cytotoxic metabolites,
      such as lipid peroxidation products and steroid hormones, which are produced
      during spermatogenesis. Because uterine fluid and seminal plasma both contain
      sorbitol, it is likely that SDH in spermatozoa converts sorbitol to fructose for
      use as an energy source.

PMID- 12185104
TI  - Ultrastructural features of the vas deferens from patients undergoing vasectomy
      and vasectomy reversal.
AB  - Despite more than 30 million vasectomies, the ultrastructural features of the
      epithelium of the vas deferens (VD) of healthy fertile men, as well as the
      effects of vasectomy at both proximal (testicular) and distal (abdominal) regions
      of the VD relative to the initial site of incision, have yet to be fully
      elucidated. In the present study, the VD from 22 fertile men undergoing vasectomy
      and 7 vasectomized men undergoing vasectomy reversal were examined by light and
      transmission electron microscopy. In fertile men, aside from cellular organelles
      involved in endocytosis and merocrine secretion, the epithelial principal cells
      showed protrusions of their apical cytoplasm between adjacent microvilli,
      referred to as "apical blebs." The latter contained solely numerous
      ribosomes/polysomes and few endoplasmic reticulum (ER) cisternae, unlike the
      presence of lysosomes, lipofuscin granules, mitochondria, and the Golgi apparatus
      in the apical principal cell cytoplasm, suggesting the segregation of organelles
      within blebs. Many apical blebs presented a bulbous extremity with a thin
      stalklike attachment connecting them to the apical principal cell surface, while
      others appeared to be isolated and well removed from it, suggesting that blebs
      are capable of detaching and being liberated into the lumen. We hypothesize that
      apical blebs represent a type of secretion, referred to as "apocrine secretion."
      In men undergoing vasectomy reversal, the VD proximal (testicular) to the
      vasectomy site showed a reduction in the size of principal cells and their
      microvilli and in the number of apical blebs. In contrast, the lumen of the VD
      distal (abdominal) to the vasectomy site was virtually abolished, with the
      epithelium reduced to a flattened layer of cells showing a paucity of organelles
      and no apical blebs, suggesting that these cells become undifferentiated in the
      absence of seminal fluids. Taken together, these data may explain, in part, the
      decreased pregnancy rate noted after vasectomy reversal despite a patent
      anastomosis.

PMID- 12185103
TI  - Higher testosterone dose impairs sperm suppression induced by a combined androgen
      progestin regimen.
AB  - In this study we compared the effects of high-dose and low-dose testosterone
      enanthate (TE) administered with the same dose of cyproterone acetate (CPA).
      Eighteen men aged 21-45 were treated with CPA 5 mg/day and with TE 100 mg/week (n
      = 9; CPA-5-100) or TE 200 mg/week (n = 9; CPA-5-200) for 16 weeks. Semen analyses
      were performed every 2 weeks; physical examination and chemistry, hematology,
      gonadotropin, and testosterone measurements were performed every 4 weeks. At week
      16 of treatment, sperm counts were significantly more suppressed in the CPA-5-100
      group than in the CPA-5-200 group. Sperm counts returned to baseline in all
      subjects after hormone administration ceased. No difference in gonadotropin
      levels was found at any time between the 2 groups. During the treatment phase,
      testosterone levels were significantly higher in the CPA-5-200 group than in the
      CPA-5-100 group. The present study confirms that CPA/TE administration induces
      profound sperm suppression. An increase in the dose of androgen resulted in less
      profound sperm suppression despite no difference in gonadotropin suppression.
      These data suggest that high testosterone levels can maintain sperm production in
      men.

PMID- 12185105
TI  - Presence of matrix metalloproteinases and tissue inhibitor of matrix
      metalloproteinase in human sperm.
AB  - The matrix metalloproteinases (MMPs) are a family of proteolytic enzymes that
      degrade protein components of the extra-cellular matrix. The necessity of
      breakdown of physical barriers in the fertilization process suggests that MMPs,
      along with their tissue inhibitors (TIMPs), might be involved in this task. We
      have examined the presence of MMP and TIMP in normal and abnormal human sperm
      samples by gel zymography and Western blot analysis. Thirty-five normal sperm
      samples and 35 abnormal sperm samples were examined in this study. Gel zymography
      showed 92-, 72-, 62-, and 28-kd molecular-weight bands exhibiting gelatin
      degrading activity in both normal and abnormal sperm samples. The 92-, 72-, and
      62-kd bands with gelatinolytic activity are consistent with pro-MMP-9, pro-MMP-2,
      and active MMP-2, respectively (pro-MMP being the zymogen of MMP). Western blot
      analysis showed the presence of TIMP-1 in both normal and abnormal sperm samples.
      A higher 28-kd activity and a lower 92-kd MMP activity in normal sperm samples
      relative to abnormal samples were detected. No marked difference in TIMP-1, 72
      kd, and 62-kd release was observed between normal and abnormal sperm samples. In
      conclusion, this is the first report of MMP activity in normal and abnormal human
      sperm samples and of TIMP presence in sperm samples. The data indicate a
      different MMP profile between normal and abnormal sperm samples, with a higher 28
      kd activity and a lower 92-kd MMP activity in normal relative to abnormal
      samples.

PMID- 12185106
TI  - Activation of protein kinase A during human sperm capacitation and acrosome
      reaction.
AB  - Spermatozoa undergo a variety of changes during their life that are prerequisites
      to their maturation and ability to fertilize eggs. Mammalian sperm capacitation
      and acrosome reaction are regulated by signal transduction systems involving
      cyclic adenosine monophosphate (cAMP) as a second messenger. This second
      messenger acts through the activation of protein kinase A (PKA) and indirectly
      regulates protein tyrosine phosphorylation. cAMP levels are controlled by a
      balance of phosphodiesterases (PDEs) and adenylyl cyclase (AC) enzymatic
      activities, which are responsible for its degradation and production,
      respectively. The aim of this study was to evaluate the possible relationship
      between the intracellular levels of cAMP and PDE and PKA activities during human
      sperm capacitation induced by fetal cord serum ultrafiltrate (FCSu) and acrosome
      reaction induced by calcium ionophore A23187. We report that PKA activity was
      higher in capacitating than in noncapacitating spermatozoa and that intracellular
      levels of cAMP decreased but that PDE activity remained constant during
      capacitation. The acrosome reaction induced by A23187 was associated with
      increases in cAMP and PKA activity but not in PDE activity. These results
      strongly suggest that net cAMP concentration is under the control of AC, since
      PDE activity is constant during sperm capacitation and the acrosome reaction.
      Moreover, the results suggest that low levels of cAMP are sufficient for
      capacitation and PKA activation and/or that the cAMP concentration measured in
      whole spermatozoa does not reflect the effective intracellular cAMP levels
      present in specific compartments of these cells.

PMID- 12185107
TI  - Effect of leukocytospermia on sperm DNA integrity: a negative effect in abnormal
      semen samples.
AB  - Controversy exists over levels of DNA integrity in the sperm of fertile and
      infertile men. In addition, the effect of leukocytospermia on sperm DNA in these
      2 groups is unclear. We decided to address these questions by collecting semen
      samples from men known or presumed to be fertile and men from infertile couples.
      Samples were analyzed and assessed for sperm concentration, motility, and
      morphology. Samples failing to meet World Health Organization (WHO) standards in
      one or more of these parameters were judged abnormal. Samples were then
      arbitrarily assigned normalized scores in each of the above parameters, and
      scores were summed to give a normalized value for overall sperm quality. DNA
      abnormality was determined by an in situ DNA denaturation test with acridine
      orange and expressed as a percentage of cells with abnormal DNA integrity (ADI).
      Assessment of 187 samples revealed a moderate inverse correlation between ADI and
      sperm quality (r =.58), although a large degree of ADI dispersion was observed in
      abnormal semen samples. The average ADI for normal and abnormal semen samples was
      18% +/- 2.8% and 36% +/- 5.8%, respectively, with the threshold of 95%
      probability set at 30%. When sorted for leukocytospermia, the difference in ADI
      between normal and abnormal semen groups without leukocytospermia was much
      smaller (17% +/- 2.2% and 22% +/- 4.6%; P =.023). Leukocytospermia had no
      significant effect on ADI in the normal semen group (P = .46); however, ADI was
      more than double the ADI in the abnormal semen group (18% +/- 2.4% and 50% +/-
      11%; P < .001). The results of our analysis show that at least 3 factors affect
      net DNA integrity in leukocytospermic samples that fail to meet WHO standards: 1)
      primary DNA damage, which is moderately inverse to sperm quality, in particular
      to sperm concentration; 2) effect of leukocytes increasing primary or provoking
      potential DNA damage in a cascade-like manner, particularly in sperm with poor
      morphology and motility; and 3) a decreasing proportion of cells with damaged DNA
      in semen with the worst quality.

PMID- 12185109
TI  - High risk corneal grafting.

PMID- 12185110
TI  - The determination of sample size in controlled clinical trials in ophthalmology.

PMID- 12185111
TI  - Minister without portfolio?

PMID- 12185113
TI  - Prevalence of blindness and low vision in Malaysian population: results from the
      National Eye Survey 1996.
AB  - BACKGROUND: A national eye survey was conducted in 1996 to determine the
      prevalence of blindness and low vision and their major causes among the Malaysian
      population of all ages. METHODS: A stratified two stage cluster sampling design
      was used to randomly select primary and secondary sampling units. Interviews,
      visual acuity tests, and eye examinations on all individuals in the sampled
      households were performed. Estimates were weighted by factors adjusting for
      selection probability, non-response, and sampling coverage. RESULTS: The overall
      response rate was 69% (that is, living quarters response rate was 72.8% and
      household response rate was 95.1%). The age adjusted prevalence of bilateral
      blindness and low vision was 0.29% (95% CI 0.19 to 0.39%), and 2.44% (95% CI 2.18
      to 2.69%) respectively. Females had a higher age adjusted prevalence of low
      vision compared to males. There was no significant difference in the prevalence
      of bilateral low vision and blindness among the four ethnic groups, and urban and
      rural residents. Cataract was the leading cause of blindness (39%) followed by
      retinal diseases (24%). Uncorrected refractive errors (48%) and cataract (36%)
      were the major causes of low vision. CONCLUSION: Malaysia has blindness and
      visual impairment rates that are comparable with other countries in the South
      East Asia region. However, cataract and uncorrected refractive errors, though
      readily treatable, are still the leading causes of blindness, suggesting the need
      for an evaluation on accessibility and availability of eye care services and
      barriers to eye care utilisation in the country.

PMID- 12185115
TI  - The prevalence and causes of blindness in the Sultanate of Oman: the Oman Eye
      Study (OES).
AB  - AIMS: To estimate the magnitude and the causes of blindness through a community
      based nationwide survey in Oman. This was conducted in 1996-7. METHODS: A
      stratified cluster random sampling procedure was used to select 12 400 people.
      The WHO/PBD standardised survey methodology was used, with suitable adaptation.
      The major causes of blindness were identified among those found blind. RESULTS: A
      total of 11 417 people were examined (response rate 91.8%) The prevalence of
      blindness in the Omani population was estimated to be 1.1% (95% CI 0.9 to 1.3),
      blindness being defined according to the WHO Tenth Revision of the International
      Classification of Diseases. Prevalence of blindness was clearly related to
      increasing age, with estimates of 0.08% for the 0-14 age group, 0.1% for the 15
      39 age group, 2.3% for the 40-59 age group, and 16.8% for the group aged 60 +.
      There was a statistically significant difference between the prevalence in
      females (1.4%) and males (0.8%). The northern and central regions had a higher
      prevalence of blindness (1.3% to 3%). The major causes of blindness were
      unoperated cataract (30.5%), trachomatous corneal opacities (23.7%), and glaucoma
      (11.5%) CONCLUSIONS: Despite an active eye healthcare programme, blindness due to
      cataract and trachoma remains a public health problem of great concern in several
      regions of the sultanate. These results highlight the need, when planning
      effective intervention strategies, to target the eye healthcare programme to the
      ageing population, with special emphasis on women.

PMID- 12185116
TI  - Education, socioeconomic status, and ocular dimensions in Chinese adults: the
      Tanjong Pagar Survey.
AB  - AIM: To relate indices of education, occupation, and socioeconomic status to
      ocular dimensions and refraction in an adult population. METHODS: A population
      based, cross sectional survey of adult Chinese aged 40-81 years residing in the
      Tanjong Pagar district in Singapore. Ocular dimensions, including axial length,
      anterior chamber depth, lens thickness, and vitreous chamber depth, were measured
      using an A-mode ultrasound device. Corneal radius of curvature and refraction
      were determined with an autorefractor, with refraction further refined
      subjectively, and lens nuclear opacity was graded clinically using the modified
      Lens Opacity Classification System III score. Data on education, occupation,
      income, and housing type were obtained from a standardised interview. RESULTS:
      Biometric data were available on 951 phakic subjects. After controlling for age,
      sex, occupation, income and housing type, higher education was associated with
      longer axial lengths (0.60 mm; 95% confidence interval (CI): 0.34, 0.85, for
      every 10 years of education), longer vitreous chambers (0.53 mm; 95% CI: 0.30,
      0.77), and more myopic refractions (-1.50 dioptres, 95% CI: -2.08, -0.92).
      Adjustment for axial length attenuated the refractive association of education (
      0.68 dioptre, 95% CI: -1.14, -0.21). Similarly, near work related occupations
      (managers, professionals, and office workers) and higher income were
      independently associated with longer axial lengths, longer vitreous chambers, and
      more myopic refractions, and adjustment for axial length attenuated the
      refractive associations. CONCLUSIONS: Adults with greater education, near work
      related occupations, and higher income are more likely to have longer axial
      lengths and vitreous chambers, and more myopic refractions. The refractive
      associations of education, occupation, and income are largely explained by
      variations in axial length.

PMID- 12185118
TI  - The use of surgical facemasks during cataract surgery: is it necessary?
AB  - AIM: To assess whether facemask utilisation by the surgeon during cataract
      surgery has any effect on the bacterial load falling onto the operative site.
      METHOD: Prospective randomised masked study. Consent was obtained from 221
      patients. Cases were randomised to wearing a new mask or not wearing any mask
      throughout the procedure. Blood agar settle plates were placed adjacent to the
      patient's head in the operative field. Duration of procedure was noted. Plates
      were incubated and read at 48 hours. Colony forming bacteria were counted and
      identified. RESULTS: There were significantly fewer organisms cultured when the
      surgeon used a facemask (p=0.0006). The majority of organisms were Staphylococcus
      epidermidis, Bacillus spp, and Diphtheroid spp; however Staphylococcus aureus and
      Pseudomonas aeruginosa were cultured on several occasions. There were no cases of
      infective complication. CONCLUSIONS: The main purpose of an operating mask is to
      prevent bacteria falling on to the operative site from the surgeon's oropharynx
      or nasopharynx with the concomitant theoretical risk of infective complication.
      Operating masks were shown to have a significant effect on the volume of
      bacterial organisms falling to the operative site; however, whether this is
      clinically significant is unknown.

PMID- 12185119
TI  - Prevalence of primary open angle glaucoma in general ophthalmic practice in the
      United Kingdom.
AB  - AIM: To estimate the predicted prevalence of primary open angle glaucoma (POAG)
      from the activity of a local ophthalmology department. METHOD: Using clinic audit
      data, the local incidence and prevalence of POAG in the registered population of
      two primary care trusts were calculated. RESULTS: The local derived prevalence
      estimate for POAG was 978 per 100 000 people aged 40-89 years (95% CI 753 to
      1272) compared with the expected prevalence from a published model of 1230 people
      per 100 000 people aged 40-89 years. CONCLUSION: The derived prevalence was not
      statistically significantly different from that predicted. Based on the published
      evidence that about half of the POAG cases are undetected, it would have been
      expected that local audit figures would have yielded figures about 50% lower than
      the epidemiological model. The main reason for this higher prevalence is thought
      to be differences in the diagnostic criteria used. This lack of consensus on the
      case definition for POAG is a deficit, which will hamper future needs assessment.

PMID- 12185117
TI  - Iris nodules associated with infectious uveitis.
AB  - BACKGROUND/AIM: Iris nodules are an uncommon clinical sign in uveitis. The
      diseases most commonly associated with iris nodules and uveitis include
      sarcoidosis, Vogt-Koyanagi-Harada syndrome, multiple sclerosis, Fuchs'
      heterochromic iridocyclitis, and metastatic infection. While many of these
      diseases may be appropriately treated with immunosuppressive medication, the
      management of infectious uveitis is antimicrobial therapy. Inappropriate
      immunosuppressive therapy may result in a poor outcome for the patient with an
      infection. Consequently, cases of uveitis with iris nodules were reviewed to
      identify clinical features that may help differentiate infection from non
      infectious inflammation. METHODS: The clinical database of 1353 consecutive
      patients evaluated at a tertiary care referral based North American uveitis
      clinic were retrospectively reviewed to identify cases of infectious uveitis with
      iris nodules. A Medline search was performed to identify additional cases. From
      these cases information regarding clinical presentation, diagnosis, treatment,
      and outcome were collected. RESULTS: Three cases (three eyes) were identified
      from the authors' own records of infectious uveitis with iris nodules. An
      additional 25 cases of infectious uveitis with iris nodules were identified in 22
      published reports. Analysis of the authors' cases and these reports showed that
      infectious uveitis with iris nodules was specifically characterised by some or
      all of the following: (1) creamy, soft appearance to the nodule(s), (2)
      unilateral disease, (3) persistence or growth of the nodule(s) despite
      corticosteroid therapy, (4) marked inflammatory response in the anterior chamber
      and/or vitreous humour, and/or (5) history suggesting a potential source of
      septic emboli. CONCLUSION: Certain features of the clinical history and
      examination are useful in the diagnosis of metastatic infection in patients
      presenting with uveitis and iris nodules.

PMID- 12185121
TI  - Ocular pulse amplitude in patients with open angle glaucoma, normal tension
      glaucoma, and ocular hypertension.
AB  - BACKGROUND/AIM: Intraocular pressure (IOP) is not a fixed constant value but
      rather has pulsatile components associated with cardiac action. The SmartLens
      dynamic observing tonometer (odc, Ophthalmic Development Company AG, Zurich,
      Switzerland) can measure and record simultaneously IOP and ocular pulse amplitude
      (OPA). It was the aim of this study to evaluate OPA in patients with primary open
      angle glaucoma (POAG) and high IOP, normal tension glaucoma (NTG), and ocular
      hypertension (OHT). Furthermore, the authors examined whether there were any
      correlations with blood pressure. METHODS: 80 subjects were divided into four
      groups (n=20): 20 patients each with POAG, NTG, and OHT and 20 volunteers without
      any ocular pathology except for cataract served as a control group. RESULTS: The
      OPA of the POAG group was not statistically significant different from the
      control group and from the OHT group. However, OPA was statistically significant
      lower (p<0.01) in the NTG group compared with all other groups. The OPA of the
      OHT group was slightly higher compared to the healthy volunteers (p=0.09) and to
      the POAG patients (p=0.09). No statistically significant correlations with blood
      pressure could be detected. A logistic regression model was established which
      identified OPA as an independent risk factor for NTG. CONCLUSIONS: The study
      demonstrated a decrease in OPA of patients suffering from NTG. Thus, measuring of
      OPA by the SmartLens dynamic observing tonometer could be helpful in the
      detection of NTG patients.

PMID- 12185122
TI  - Quantifying relative afferent pupillary defects using a Sbisa bar.
AB  - AIM: To compare the Sbisa bar (Bagolini filter bar) with neutral density filters
      (NDF) in quantifying relative afferent pupillary defects (RAPD). METHODS: 11
      patients with a RAPD were graded and a neutral density filter bar was used to
      quantify the RAPD. This was repeated using the Sbisa bar. The Sbisa bar (Bagolini
      filter bar) is used by orthoptists to quantify density of suppression in
      amblyopia and is of a similar construct to NDFs. Before this clinical part of the
      study the luminance for each filter was measured, which enabled a direct
      comparison to be made. RESULTS: In the analysis of patients with RAPD a high
      correlation was found when comparing the Sbisa and NDF bars r = 0.95. This was
      statistically significant (p = <0.001). Correlation was also high when the
      luminance values for the filters were substituted for the clinical readings (r =
      0.92; p=<0.001). CONCLUSION: The Sbisa bar is a comparable instrument to the NDF
      bar in measuring RAPD. Its availability in the clinical situation makes it a
      practical choice.

PMID- 12185123
TI  - Systemic cyclosporin A in high failure risk, repeated corneal transplantation.
AB  - AIM: To evaluate the efficacy of oral cyclosporin A in the prevention and
      treatment of immune graft rejection in heavily vascularised, repeated
      keratoplasties with high risk for failure. METHODS: 21 consecutive patients with
      28 repeated corneal transplants and four quadrant vascularised recipient bed were
      treated with oral cyclosporin A for an average period of 12 months (range 1-41
      months) and followed for an average period of 26.6 months (range 6-106 months).
      The average cyclosporin A blood level was 325 ng/ml (range 180-421 ng/ml). Within
      this group of 21 patients, another 12 regrafts were not treated with cyclosporin
      A and served as a control group. RESULTS: Nine of the 28 regrafts (32%) treated
      with cyclosporin A remained clear. The Kaplan-Meier curve showed a constant
      decline in survival of the treated grafts, although the survival proportion
      during the first year of treatment was statistically higher for the treated group
      compared with the untreated group. Once immune regraft rejection occurred, the
      regraft failed despite treatment with cyclosporin A and extensive topical and
      systemic corticosteroids. Nine regrafts (32%) had immune graft rejection and all
      ultimately failed compared with five in the untreated regrafts (42%, p = NS). Ten
      other regrafts (36%) in the treatment group failed due to causes other than
      immune regraft rejection. CONCLUSIONS: Systemic cyclosporin A has a limited
      beneficial effect in preventing immune graft rejection in repeated corneal
      transplants in a highly vascularised corneal bed. When immune graft rejection
      occurs in such regrafts, the prognosis is poor despite aggressive medical
      treatment. Causes other than immune regraft rejection may also result in poor
      visual outcome in patients with clear regrafts.

PMID- 12185125
TI  - Correlation between visual function and visual ability in patients with uveitis.
AB  - AIM: To investigate the correlation between tests of visual function and
      perceived visual ability recorded with a quality of life questionnaire for
      patients with uveitis. METHODS: 132 patients with various types of uveitis were
      studied. High (monocular and binocular) and low (binocular) contrast logMAR
      letter acuities were recorded using a Bailey-Lovie chart. Contrast sensitivity
      (binocular) was determined using a Pelli-Robson chart. Vision related quality of
      life was assessed using the Vision Specific Quality of Life (VQOL) questionnaire.
      RESULTS: VQOL declined with reduced performance on the following tests: binocular
      high contrast visual acuity (p = 0.0011), high contrast visual acuity of the
      better eye (p = 0.0012), contrast sensitivity (p = 0.005), binocular low contrast
      visual acuity (p = 0.0065), and high contrast visual acuity of the worse eye (p =
      0.015). Stepwise multiple regression analysis revealed binocular high contrast
      visual acuity (p <0.01) to be the only visual function adequate to predict VQOL.
      The age of the patient was also significantly associated with perceived visual
      ability (p <0.001). CONCLUSIONS: Binocular high contrast visual acuity is a good
      measure of how uveitis patients perform in real life situations. Vision quality
      of life is worst in younger patients with poor binocular visual acuity.

PMID- 12185126
TI  - Ultrasound biomicroscopy and its value in predicting the long term outcome of
      viscocanalostomy.
AB  - AIMS: To examine whether the early postoperative morphology at the site of
      sclerectomy, as visualised by ultrasound biomicroscopy (UBM), is an indicator of
      the mechanisms that lower intraocular pressure (IOP) and/or predictors of the
      long term outcome of viscocanalostomy. METHODS: 15 eyes of 14 patients with
      medically uncontrolled open angle glaucoma and no history of surgery underwent
      viscocanalostomy according to Stegmann's technique. Ultrasound biomicroscopy was
      performed during the first month after surgery. The following parameters were
      assessed: dimensions of the intrascleral "lake," presence of a filtering bleb,
      presence of a subconjunctival cavity or a suprachoroidal hypoechoic area, and the
      thickness of the residual trabeculocorneal membrane. A complete ophthalmological
      examination was performed the day before and the day after surgery. Follow up
      visits were scheduled 1 week, 4 weeks, 6 months, and 12 months after surgery.
      RESULTS: At 1 year successful control of IOP (<20 mm Hg) was achieved without
      further manipulation or medication in six of 15 eyes. The size of the
      intrascleral "lake" (average 0.62 mm(3)) did not correlate with later IOP;
      however, a visible route under the scleral flap and accidental perforation of the
      trabeculocorneal membrane were associated with long term lowering of IOP. Normal
      thickness of the trabeculocorneal membrane (0.10-0.15 mm) was indicative of IOP
      control with and without medication. When UBM showed an early collapse of the
      intrascleral cavity, control of IOP was not achieved. Other UBM findings did not
      predict long term function. CONCLUSION: In accordance with previous studies, the
      authors found that UBM examination is a useful method to evaluate outflow
      mechanisms after glaucoma surgery. This study shows that UBM imaging of external
      filtration during the early postoperative period can be used to predict the
      success of viscocanalostomy. However, to establish conclusively what parameters
      of UBM predict successful viscocanalostomy a larger number of patients must be
      studied.

PMID- 12185127
TI  - Hypertensive retinopathy and incident coronary heart disease in high risk men.
AB  - BACKGROUND/AIM: Although routine ophthalmoscopy is recommended in the evaluation
      of people with hypertension, the prognostic significance of retinopathy is
      unknown. The purpose of this study is to determine if hypertensive retinopathy
      predicts coronary heart disease (CHD). METHODS: A prospective cohort study
      involving 560 hypertensive, hyperlipidaemic, middle aged men enrolled in the
      Lipid Research Clinic's Coronary Primary Prevention Trial. Signs of hypertensive
      retinopathy (generalised and focal arteriolar narrowing, arteriovenous nicking,
      widened arteriolar light reflex, retinal haemorrhage and exudates,
      microaneurysms, and disc swelling) were evaluated by direct funduscopy during a
      baseline examination by study physicians. Incident CHD events were ascertained
      from hospital records, necropsy reports, and death certificates, and reviewed by
      a masked panel of cardiologists. RESULTS: There were 51 definite CHD events
      (definite CHD deaths or myocardial infarctions) during a median follow up of 7.8
      years. After adjusting for age, blood pressure, electrocardiographic
      manifestations of left ventricular hypertrophy, cholesterol levels and treatment,
      glucose and creatinine levels, and smoking status in proportional hazards
      analysis, the presence of hypertensive retinopathy predicted a doubling of the
      risk of definite CHD events (relative risk 2.1; 95% confidence interval (CI) 1.0
      to 4.2 ). The presence of either generalised or focal arteriolar narrowing
      predicted almost a tripling of the risk (relative risk 2.9; 95% CI 1.3 to 6.2).
      Associations were similar for stage 1 hypertension (systolic and diastolic blood
      pressures of 140-159 and 90-99 mm Hg, respectively) and for other CHD end points.
      CONCLUSION: Hypertensive retinopathy predicts CHD in high risk men, independent
      of blood pressure and CHD risk factors. The data support the concept that retinal
      microvascular changes are markers of blood pressure damage and may be useful in
      risk stratification and in the tailoring of hypertension treatment decisions.

PMID- 12185128
TI  - Retinal microvascular abnormalities and blood pressure in older people: the
      Cardiovascular Health Study.
AB  - AIM: To examine the relation between blood pressure and retinal microvascular
      abnormalities in older people. METHODS: The Cardiovascular Health Study is a
      prospective cohort study conducted in four US communities initiated in 1989 to
      1990. Blood pressure was measured according to standardised protocols at each
      examination. During the 1997-8 examination, retinal photographs were taken of
      2405 people aged 69-97 years (2056 without diabetes and 349 with diabetes). Signs
      of focal microvascular abnormalities (focal arteriolar narrowing, arteriovenous
      nicking, and retinopathy) were evaluated from photographs according to
      standardised methods. To quantify generalised arteriolar narrowing, the
      photographs were digitised and diameters of individual arterioles were measured
      and summarised. RESULTS: In non-diabetic people, elevated concurrent blood
      pressure taken at the time of retinal photography was strongly associated with
      presence of all retinal microvascular lesions. The multivariable adjusted odds
      ratios, comparing the highest to lowest quintile of concurrent systolic blood
      pressure, were 4.0 (95% confidence intervals (CI): 2.4 to 6.9, p test of
      trend<0.001) for focal arteriolar narrowing, 2.9 (95% CI: 1.6 to 5.3, p<0.001)
      for arteriovenous nicking, 2.8 (95% CI: 1.5 to 5.2, p<0.001) for retinopathy, and
      2.1 (95% CI: 1.4 to 3.1, p<0.001) for generalised arteriolar narrowing.
      Generalised arteriolar narrowing and possibly arteriovenous nicking were also
      significantly associated with past blood pressure measured up to 8 years before
      retinal photography, even after adjustment for concurrent blood pressure. These
      associations were somewhat weaker in people with diabetes. CONCLUSIONS: Retinal
      microvascular abnormalities are related to elevated concurrent blood pressure in
      older people. Additionally, generalised retinal arteriolar narrowing and possibly
      arteriovenous nicking are related to previously elevated blood pressure,
      independent of concurrent blood pressure. These data suggest that retinal
      microvascular changes reflect severity and duration of hypertension.

PMID- 12185129
TI  - Diabetic retinopathy among self reported diabetics in southern India: a
      population based assessment.
AB  - AIMS: To estimate the prevalence of diabetic retinopathy among self reported
      diabetics in a population of southern India. METHODS: A cross sectional sample of
      subjects aged 50 years and older was selected using a cluster sampling technique
      from Palakkad district of Kerala state. Eligible subjects were identified through
      a door to door survey. Ocular examinations including visual acuity and anterior
      and posterior segment examinations were performed at preselected sites within
      clusters. History of diabetes was elicited, and height, weight, and blood
      pressure were measured for all subjects. RESULTS: Among the 5212 examined people
      (92% response rate), 68 (26.2%) of 260 people with self reported history of
      diabetes had diabetic retinopathy. The age-sex adjusted prevalence of diabetes
      among people aged 50 years and older was 5.1% (95% CI 3.9, 6.3, deff 4.33) and of
      diabetic retinopathy among the diabetics was 26.8% (95% CI: 19.2, 34.4, deff
      1.99). Non-proliferative diabetic retinopathy (94.1%) was the most common form of
      retinopathy seen. Two eyes were blind (presenting vision <6/60) as a result of
      retinopathy. CONCLUSION: Preventive strategies have to be evolved to ensure that
      blindness due to diabetic retinopathy does not become a public health problem in
      India. Further studies are required to understand the risk factors for
      retinopathy and vision loss in this population.

PMID- 12185131
TI  - Face recognition in age related macular degeneration: perceived disability,
      measured disability, and performance with a bioptic device.
AB  - AIMS: (1) To explore the relation between performance on tasks of familiar face
      recognition (FFR) and face expression difference discrimination (FED) with both
      perceived disability in face recognition and clinical measures of visual function
      in subjects with age related macular degeneration (AMD). (2) To quantify the gain
      in performance for face recognition tasks when subjects use a bioptic telescopic
      low vision device. METHODS: 30 subjects with AMD (age range 66-90 years; visual
      acuity 0.4-1.4 logMAR) were recruited for the study. Perceived (self rated)
      disability in face recognition was assessed by an eight item questionnaire
      covering a range of issues relating to face recognition. Visual functions
      measured were distance visual acuity (ETDRS logMAR charts), continuous text
      reading acuity (MNRead charts), contrast sensitivity (Pelli-Robson chart), and
      colour vision (large panel D-15). In the FFR task, images of famous people had to
      be identified. FED was assessed by a forced choice test where subjects had to
      decide which one of four images showed a different facial expression. These tasks
      were repeated with subjects using a bioptic device. RESULTS: Overall perceived
      disability in face recognition did not correlate with performance on either task,
      although a specific item on difficulty recognising familiar faces did correlate
      with FFR (r = 0.49, p<0.05). FFR performance was most closely related to distance
      acuity (r = -0.69, p<0.001), while FED performance was most closely related to
      continuous text reading acuity (r = -0.79, p<0.001). In multiple regression,
      neither contrast sensitivity nor colour vision significantly increased the
      explained variance. When using a bioptic telescope, FFR performance improved in
      86% of subjects (median gain = 49%; p<0.001), while FED performance increased in
      79% of subjects (median gain = 50%; p<0.01). CONCLUSION: Distance and reading
      visual acuity are closely associated with measured task performance in FFR and
      FED. A bioptic low vision device can offer a significant improvement in
      performance for face recognition tasks, and may be useful in reducing the
      handicap associated with this disability. There is, however, little evidence for
      a correlation between self rated difficulty in face recognition and measured
      performance for either task. Further work is needed to explore the complex
      relation between the perception of disability and measured performance.

PMID- 12185132
TI  - Increase of mitochondrial DNA in blood cells of patients with Leber's hereditary
      optic neuropathy with 11778 mutation.
AB  - AIMS: To investigate the change of mitochondrial DNA (mtDNA) content in Leber's
      hereditary optic neuropathy (LHON) with 11778 mutation. METHODS: Mitochondrial
      DNA content in 27 LHON patients with 11778 mutation, 26 asymptomatic maternal
      relatives, and 23 normal controls was measured using a competitive polymerase
      chain reaction (PCR) method. RESULTS: The mean relative content of mtDNA (with
      respect to the beta actin gene) in LHON patients, asymptomatic maternal
      relatives, and normal controls was 245.5 (162.3), 238.2 (118.4), and 156.5
      (61.6), respectively. There was a statistically significant difference between
      patients and controls and between relatives and controls. However, no
      statistically significant difference between patients and unaffected relatives
      was found. There was no statistically significant difference in the relative
      content of mtDNA between all males and females carrying 11778 mtDNA mutation
      CONCLUSION: The results suggest that the increase in mtDNA content in LHON
      patients with 11778 mtDNA mutation may be due to a compensatory effect for
      respiratory chain defects of mitochondria. However, the increase of mtDNA content
      is the result rather than the cause of defective mtDNA. It still cannot explain
      the pathogenesis of LHON.

PMID- 12185133
TI  - Surgical punctal occlusion: a prospective study.
AB  - AIMS: To assess the outcome of a surgical punctal occlusion technique. METHOD:
      Prospectively, 11 consecutive patients (26 puncta) with severe dry eyes
      recalcitrant to maximal medical therapy underwent permanent punctal occlusion at
      a tertiary eye care centre between January 1999 and December 2000. The epithelium
      of the punctum and the vertical portion of the canaliculus was removed with a
      corneal rust ring burr. The bared punctum-canaliculus complex was closed with a 6
      0 chromic suture. Success was measured by the complete functional occlusion of
      the punctum, tear function tests, and patients' response. RESULT: Five males and
      nine females, aged 26-77 enrolled in the study with three patients later
      excluded. As of November 2001, the remaining 11 patients had follow up ranging
      from 14 to 34 months (mean 24 months; median 24 months). 24 puncta (or 92%)
      remained occluded, including four puncta which showed anatomical reopening. Seven
      out of 11 patients (63.6%) stated they had symptomatic improvement regardless of
      their objective findings. CONCLUSION: This technique resulted in a 92% permanent
      occlusion of the puncta and compared favourably with other reported techniques.
      Punctal occlusion does not appear to correlate well with Schirmer tests, the
      frequency of lubrication, and/or subjective feelings in these patients.

PMID- 12185134
TI  - Emmetropisation following preterm birth.
AB  - BACKGROUND/AIMS: Even in the absence of retinopathy of prematurity (ROP),
      premature birth signals increased risk for abnormal refractive development. The
      present study examined the relation between clinical risk factors and refractive
      development among preterm infants without ROP. METHODS: Cycloplegic refraction
      was measured at birth, term, 6, 12, and 48 months corrected age in a cohort of 59
      preterm infants. Detailed perinatal history and cranial ultrasound data were
      collected. 40 full term (plus or minus 2 weeks) subjects were tested at birth, 6,
      and 12 months old. RESULTS: Myopia and anisometropia were associated with
      prematurity (p<0.05). More variation in astigmatic axis was found among preterm
      infants (p<0.05) and a trend for more astigmatism (p<0.1). Emmetropisation
      occurred in the preterm infants so that at term age they did not differ from the
      fullterm group in astigmatism or anisometropia. However, preterm infants remained
      more myopic (less hyperopic) than the fullterm group at term (p<0.05) and those
      infants born <1500 g remained more anisometropic than their peers until 6 months
      (p<0.05). Infants with abnormal cranial ultrasound were at risk for higher
      hyperopia (p<0.05). Other clinical risk factors were not associated with
      differences in refractive development. At 4 years of age 19% of the preterm group
      had clinically significant refractive errors. CONCLUSION: Preterm infants without
      ROP had high rates of refractive error. The early emmetropisation process
      differed from that of the fullterm group but neither clinical risk factors nor
      measures of early refractive error were predictive of refractive outcome at 4
      years.

PMID- 12185135
TI  - Factors associated with undercorrected refractive errors in an older population:
      the Blue Mountains Eye Study.
AB  - AIMS: To identify characteristics of people with clinically relevant
      undercorrected refractive errors. METHODS: The Blue Mountains Eye Study was a
      population based survey of 3654 Australians aged 49-97 years. Examinations
      included a standardised refraction and measurement of presenting and best
      corrected visual acuity. Clinically relevant undercorrected refractive error was
      defined as improvement of >/=10 letters (2+ lines on the logMAR chart) in
      subjects with presenting acuity 6/9 or worse. Associations with a range of
      demographic and ocular variables were explored, adjusting for age and sex,
      presented as odds ratios (OR) with 95% confidence intervals (CI). RESULTS:
      Undercorrected refractive error was present in 814/3654 subjects (10.2%). Older
      age (p <0.001), hyperopia (OR 1.45, CI 1.15 to 1.83), longer interval from last
      eye examination (p <0.001), past occupation as tradesperson (OR 1.64, 1.13 to
      3.29) or labourer (OR 2.00, CI 1.39 to 2.89), receipt of government pension (OR
      1.47, CI 1.12 to 1.94), and living alone (OR 1.34, CI 1.05 to 1.72) were all
      associated with undercorrected refractive error. Past or current use of distance
      glasses (OR 0.25, CI 0.20 to 0.32) and driving (OR 0.67, CI 0.52 to 0.86) were
      associated with a lower prevalence. CONCLUSIONS: Increasing age and measures of
      socioeconomic disadvantage and isolation were found to predict undercorrected
      refractive error. Given the documented impacts from correctable visual
      impairment, these findings suggest a need to target education and eye care
      services.

PMID- 12185136
TI  - Confocal microscopic examination of trabecular meshwork removed during ab externo
      trabeculectomy.
AB  - AIMS: The aim of the ab externo trabeculectomy (AET) is to remove the external
      portion of the trabecular meshwork (ETM) responsible for the main aqueous outflow
      resistance in glaucoma patients, with no opening of the anterior chamber. ETM
      characteristics were evaluated with a confocal microscope. METHODS: A prospective
      comparative observational case series was performed in 60 consecutive medically
      treated patients with primary open angle glaucoma and eight postmortem normal
      donors' eyes that underwent AET. Once deroofing the Schlemm' s canal (SC), a
      deeper dissection led to removal of a coherent membrane (ETM) which allowed
      satisfactory aqueous egress through the remaining intact internal trabecular
      meshwork (TM) layers. After fixation with acetone and immunostaining with anti
      vimentin antibody, ETM were analysed with a confocal microscope. RESULTS:
      Glaucomatous ETM (mean thickness: 29.5 (7.6) micro m) were characterised by a
      severe paucicellularity compared with the controls (respectively 37.3 (9.7)
      cells/area and 167.5 (24.9) cells/area, p<10(-4)). ETM analysis showed
      involvement of both cribriform and corneoscleral layers. ETM cell density was
      significantly decreased in case of preoperative fluorometholone instillation.
      CONCLUSION: Paucicellularity of glaucomatous TM is confirmed by this original
      technique. Structural characteristics of the ETM, whose removal allows
      satisfactory aqueous egress, suggest that aqueous outflow resistance not only
      involves inner wall of SC and juxtacanalicular meshwork but also corneoscleral
      trabecular layers.

PMID- 12185137
TI  - Melatonin MT-1-receptor immunoreactivity in the human eye.
AB  - AIM: To examine the distribution of melatonin 1a (MT1) receptors in the human
      eye. METHODS: Seven normal human eyes were examined by immunohistochemical
      staining of paraffin sections, using an anti-MT1 primary antibody and an ABC
      detection system. RESULTS: MT1 receptor immunoreactivity (MT1-IR) was detected
      primarily in the inner segments of rods and cones and in retinal ganglion cells.
      In addition, MT1-IR was present in the adventitia of retinal arteries and veins,
      including the papillary region, but absent in ciliary and choroidal vessels. Mild
      staining of corneal endothelial cells and keratocytes was observed in all but two
      eyes. CONCLUSION: MT1-IR is present in various ocular tissues with the highest
      density in photoreceptor cells and ganglion cells. The physiological function of
      these receptors deserves further investigation.

PMID- 12185138
TI  - Modulation of hydrogen peroxide induced injury to corneal endothelium by virus
      mediated catalase gene transfer.
AB  - AIM: To examine the effect of catalase gene transfer on survival of corneal
      endothelial cells (EC) following challenge with hydrogen peroxide (H(2)O(2)) in
      an ex vivo model of oxidative stress. METHODS: A recombinant adenovirus vector
      (AdCL) was used to transfer human catalase cDNA into EC of whole thickness rabbit
      corneas ex vivo. The resulting catalase protein concentration was measured in
      corneal lysates by ELISA; catalase functional activity in lysates was determined
      using a H(2)O(2) activity assay. To examine the morphological effects of catalase
      gene transfer in modulation of H(2)O(2) induced injury, transduced corneas were
      maintained in ex vivo culture and challenged with H(2)O(2). Laser scanning
      confocal microscopy was used to image EC injury. Cell density, cell morphology,
      and ratios of viable to necrotic cells were determined. RESULTS: Following
      incubation with AdCL, catalase expression reached maximum at 5-7 days. Corneas
      transduced with AdCL showed increased EC cell survival following challenge with
      H(2)O(2) on day 3 when compared to null vector control or mock infected corneas.
      CONCLUSIONS: Ex vivo catalase gene transfer can protect EC from death mediated by
      H(2)O(2). This gene based approach to the protection of corneal endothelium from
      oxidative stress may have application in prevention of EC loss in pathological
      conditions in which H(2)O(2) is involved and in ex vivo donor corneal storage
      before transplantation.

PMID- 12185139
TI  - Ophthalmic artery occlusion following pars plana vitrectomy in a patient with
      Terson's syndrome.

PMID- 12185140
TI  - Retinal arteriolar calcification in a patient with chronic renal failure.

PMID- 12185141
TI  - Acute bilateral blindness caused by accidental methanol intoxication during fire
      "eating".

PMID- 12185142
TI  - Central serous chorioretinopathy after inhaled steroid use for post-mycoplasmal
      bronchospasm.

PMID- 12185143
TI  - Two rare causes of posterior ischaemic optic neuropathy: eosinophilic fasciitis
      and Wegener's granulomatosis.

PMID- 12185144
TI  - Concentration of intravitreally injected triamcinolone acetonide in aqueous
      humour.

PMID- 12185145
TI  - Dacryocystorhinostomy for partial nasolacrimal obstruction.

PMID- 12185146
TI  - Quantifying corneal endothelial cell death.

PMID- 12185148
TI  - Herpes simplex encephalitis.

PMID- 12185149
TI  - Multiple sclerosis in Malta in 1999.

PMID- 12185150
TI  - Impact of early intervention on outcome following mild head injury in adults.

PMID- 12185151
TI  - The effects of deep brain stimulation and levodopa on postural sway in subjects
      with Parkinson's disease.

PMID- 12185152
TI  - Functional weakness and sensory disturbance.
AB  - In the diagnosis of functional weakness and sensory disturbance, positive
      physical signs are as important as absence of signs of disease. Motor signs,
      particularly Hoover's sign, are more reliable than sensory signs, but none should
      be used in isolation and must be interpreted in the overall context of the
      presentation. It should be borne in mind that a patient may have both a
      functional and an organic disorder.

PMID- 12185153
TI  - A randomised placebo controlled exploratory study of vitamin B-12, lofepramine,
      and L-phenylalanine (the "Cari Loder regime") in the treatment of multiple
      sclerosis.
AB  - OBJECTIVE: To determine whether combination therapy with lofepramine, L
      phenylalanine, and intramuscular vitamin B-12 (the "Cari Loder regime") reduces
      disability in patients with multiple sclerosis. METHODS: A placebo controlled,
      double blind, randomised study carried out in five United Kingdom centres on
      outpatients with clinically definite multiple sclerosis, measurable disability on
      Guy's neurological disability scale (GNDS), no relapse in the preceding six
      months, and not on antidepressant drugs. Over 24 weeks all patients received
      vitamin B-12, 1 mg intramuscularly weekly, and either lofepramine 70 mg and L
      phenylalanine 500 mg twice daily, or matching placebo tablets. Outcome was
      assessed using the GNDS, the Kurtzke expanded disability status scale; the Beck
      depression inventory, the Chalder fatigue scale, and the Gulick MS specific
      symptom scale. RESULTS: 138 patients were entered, and two were lost from each
      group. There was no statistically significant difference between the groups at
      entry or at follow up. Analysis of covariance suggested that treated patients had
      better outcomes on four of the five scales used. Both groups showed a reduction
      of 2 GNDS points within the first two weeks, and when data from all time points
      were considered, the treated group had a significant improvement of 0.6 GNDS
      points from two weeks onwards. CONCLUSIONS: Patients with multiple sclerosis
      improved by 2 GNDS points after starting vitamin B-12 injections. The addition of
      lofepramine and L-phenylalanine added a further 0.6 points benefit. More research
      is needed to confirm and explore the significance of this clinically small
      difference.

PMID- 12185154
TI  - Home based management in multiple sclerosis: results of a randomised controlled
      trial.
AB  - BACKGROUND: Home based medical care is a popular alternative to standard hospital
      care but there is uncertainty about its cost-effectiveness. OBJECTIVES: To
      compare the effectiveness and the costs of multidisciplinary home based care in
      multiple sclerosis with hospital care in a prospective randomised controlled
      trial with a one year follow up. METHODS: 201 patients with clinically definite
      multiple sclerosis were studied. They were randomised in a ratio 2:1 to an
      intervention group (133) or a control group (68). They were assessed at baseline
      and one year after randomisation with validated measures of physical and
      psychological impairment and quality of life (SF-36 health survey). The costs to
      the National Health Service over the one year follow up were calculated by a cost
      minimisation analysis. RESULTS: There were no differences in functional status
      between the home based care group and the hospital group. There was a significant
      difference between the two groups favouring home based management in four SF-36
      health dimensions-general health, bodily pain, role-emotional, and social
      functioning (all p < or = 0.001). The cost of home based care was slightly less
      (822 euros/patient/year) than hospital care, mainly as a result of a reduction in
      hospital admissions. CONCLUSIONS: Comprehensive planning of home based
      intervention implemented by an interdisciplinary team and designed specifically
      for people with multiple sclerosis may provide a cost-effective approach to
      management and improve the quality of life.

PMID- 12185155
TI  - Multiple sclerosis in Malta in 1999: an update.
AB  - OBJECTIVES: To ascertain the prevalence of multiple sclerosis (MS) in the islands
      of Malta and compare it with a previous study undertaken 21 years earlier, when a
      remarkably low prevalence was found. METHOD: Deaths with MS on the death
      certificate since the last study were reviewed. Sources of information about new
      patients were the Hospital Activity Analysis scheme, the MS Society of Malta, the
      records of the state hospitals, long stay private hospitals and nursing homes,
      lists provided by the state pharmacies, and magnetic resonance imaging,
      cerebrospinal fluid, and evoked response studies. Prevalence day was 1 January
      1999. The Poser classification was used. RESULTS: Since 1978, 17 patients had
      died with a verified diagnosis of MS on the death certificate. They included all
      10 deaths with MS from the original study and two immigrants. Fifty patients had
      clinically definite MS (CDMS) and 13 clinically probable MS (CPMS). The
      prevalence of CDMS was 13.2/100 000 (male 11.2, female 15.2). The prevalence of
      CDMS and CPMS combined was 16.7/100,000 (male 13.3, female 19.9). The annual
      incidence was 0.7/100,000. Twelve patients were found with CDMS among the 7213
      immigrants resident in Malta (166/100,000). The expected rate was 1/100,000,
      determined at Maltese born rates. There were major changes in the population
      distribution during the 21 years between the two studies, with a big increase in
      the age groups with a high risk of MS. There is a longer expectation of life and
      the diagnosis in now made earlier. CONCLUSION: Malta still has a low MS
      prevalence. In comparison with Sicily and other Mediterranean countries of Europe
      it offers an opportunity to ascertain the genetic and environmental factors
      responsible for the disease.

PMID- 12185156
TI  - Genetic variability in the insulin signalling pathway may contribute to the risk
      of late onset Alzheimer's disease.
AB  - OBJECTIVE: To test the hypothesis that polymorphic variation in insulin
      signalling genes may underlie the shared risk of dysfunctional insulin signalling
      and late onset Alzheimer's disease (AD). The p85alpha subunit of phosphatidyl
      inositol 3 kinase (PIK3R1) and the regulatory subunit 3 of protein phosphatase 1
      (PPP1R3) were selected as candidate genes because both encode key proteins
      involved in insulin signalling and because polymorphisms in these genes have been
      previously implicated in insulin resistance or type II diabetes. METHODS:
      Analysis of the Met326Ile PIK3R1 and the Asp905Tyr PPP1R3 polymorphisms in 202
      patients with late onset AD and 160 or 170 age matched normal subjects. RESULTS:
      Logistic regression analysis using the recessive genetic model showed significant
      differences in genotype and allelic frequencies between the AD group and normal
      controls (genotypes: odds ratio (OR) 2.09, 95% confidence interval (CI) 1.17 to
      3.74, p = 0.01; alleles: OR 1.99, 95% CI 1.17 to 3.40, p = 0.01) for the
      Met326Ile PIK3R1 polymorphism that were female specific. Additionally, in the
      dominant genetic model a marginally significant association in genotype
      frequencies between the Asp905Tyr PPP1R3 polymorphism and AD was observed
      (genotypes: OR 1.85, 95% CI 1.03 to 3.30, p = 0.04; alleles: OR 1.68, 95% CI 0.98
      to 2.88, p = 0.06). Both polymorphisms were tested for their interactions with
      sex and the presence of the apolipoprotein E epsilon 4 allele. CONCLUSIONS: The
      results support the hypothesis for a common genetic aetiology predisposing to
      insulin resistance and AD.

PMID- 12185157
TI  - Effects of deep brain stimulation and levodopa on postural sway in Parkinson's
      disease.
AB  - OBJECTIVE: To quantify postural sway in subjects with Parkinson's disease and
      elderly controls, and determine the effects of Parkinson's disease, deep brain
      stimulation, levodopa, and their interactions on postural control during quiet
      stance. METHODS: Centre of foot pressure (CoP) displacement under each foot was
      measured during three 60 s trials of quiet stance with eyes open in 11 controls
      and six patients with Parkinson's disease. Subjects with Parkinson's disease were
      tested in four treatment conditions: off both deep brain stimulation and levodopa
      (off condition); on deep brain stimulation; on levodopa; and on both deep brain
      stimulation and levodopa. The variables extracted from CoP included: root mean
      square distance (rms), mean velocity, 95% power frequency (f(95%)), area of the
      95% confidence ellipse (ellipse area), direction of its major axis (mdir), and
      postural asymmetry between the feet. RESULTS: rms and area of postural sway were
      larger than normal in subjects with Parkinson's disease in the off condition,
      increased further with levodopa, and significantly decreased with deep brain
      stimulation. Mean velocity and f(95%) were also larger than normal but were
      restored to normal by all treatments, especially by deep brain stimulation. The
      combined effect of deep brain stimulation and levodopa resulted in a postural
      sway that was an average of the effect of each treatment individually. Levodopa
      increased sway more in the mediolateral than in the anterior-posterior direction.
      Subjects with Parkinson's disease had asymmetrical mean velocity and f(95%)
      between the feet, and this asymmetry increased with levodopa but decreased with
      deep brain stimulation. The f(95%) of the CoP correlated with tremor, posture,
      and gait subcomponents of the unified Parkinson's disease rating scale.
      CONCLUSIONS: Subjects with Parkinson's disease have abnormal postural sway in
      stance. Treatment with levodopa increases postural sway abnormalities, whereas
      treatment with deep brain stimulation improves postural sway. Quantitative
      evaluation of static posturography may be a useful adjunct to clinical measures
      in patients with Parkinson's disease.

PMID- 12185158
TI  - Dual channel deep brain stimulation system (Kinetra) for Parkinson's disease and
      essential tremor: a prospective multicentre open label clinical study.
AB  - OBJECTIVES: To evaluate the safety and efficacy of a new dual channel stimulator
      (Kinetra) in patients with severe Parkinson's disease (PD) or essential tremor
      (ET). METHODS: 111 patients with PD and 18 with ET were studied. Leads were
      implanted into the subthalamic nucleus (STN) or internal globus pallidus of
      patients with the akinetic/rigid type of PD. Leads were implanted into the
      ventral intermediate nucleus (VIM) of the thalamus or the STN in patients with
      the tremor dominant type of PD and in those with ET. Technical data on the device
      and adverse events occurring during the study were documented. Patients were
      assessed with established and validated clinical scales before surgery and at
      three and six months' follow up. RESULTS: No device failure or unexpected adverse
      events occurred during the study. The dual channel stimulator used in stimulation
      of the STN, internal globus pallidus, and VIM in PD and ET was as safe and
      effective as the single channel stimulators in use. Mortality, morbidity, and
      infections were documented in the 129 treated patients. The parameter settings
      were similar to those usually programmed with single channel stimulators. Time
      spent in the operating room to implant the Kinetra system was systematically
      documented. In the PD group, improvement in the unified Parkinson's disease
      rating scale motor score, decrease in medication OFF periods, and reduced
      levodopa induced dyskinesia by bilateral STN stimulation were similar to those
      previously reported with bilaterally applied single channel stimulators. In the
      ET group upper and lower limb tremor scores were reduced by VIM stimulation.
      Activities of daily living improved in both disease groups. CONCLUSION: The
      Kinetra facilitated bilateral deep brain stimulation implantation surgery and is
      easy to use. It offers more advantages for the patient than the single channel
      stimulators; consequently, this new device may be recommended to treat patients
      with severe PD and ET.

PMID- 12185159
TI  - Long term psychosocial outcomes after mild head injury in early childhood.
AB  - OBJECTIVES: The question of whether any adverse cognitive or psychosocial
      outcomes occur after mild head injury in early childhood has evoked considerable
      controversy. This study examined mild head injury before age 10 and potential
      differences in late childhood/early adolescence as a function of severity of mild
      injury and age at injury. METHODS: A fully prospective longitudinal design
      tracked a large birth cohort of children. Confirmed cases of mild head injury
      before age 10 were divided on the basis of outpatient medical attention (n=64-84)
      or inpatient observation (hospital overnight; n=26-28 ) and compared with the non
      injured remainder of the cohort (reference group; n=613-807). A range of pre
      injury and post-injury child and family characteristics were used to control for
      any potential confounds. Outcome after injury before and after age 5 was also
      assessed. RESULTS: After accounting for several demographic, family, and pre
      injury characteristics, the inpatient but not the outpatient group displayed
      increased hyperactivity/inattention and conduct disorder between ages 10 to 13,
      as rated by both mothers and teachers. Psychosocial deficits were more prevalent
      in the inpatient subgroup injured before age 5. No clear effects were evident for
      various cognitive/academic measures, irrespective of severity of mild injury or
      age at injury. CONCLUSIONS: Most cases of mild head injury in young children do
      not produce any adverse effects, but long term problems in psychosocial function
      are possible in more severe cases, perhaps especially when this event occurs
      during the preschool years. The view that all mild head injuries in children are
      benign events requires revision and more objective measures are required to
      identify cases at risk.

PMID- 12185160
TI  - Semiquantitative analysis of corpus callosum injury using magnetic resonance
      imaging indicates clinical severity in patients with diffuse axonal injury.
AB  - OBJECTIVE: To evaluate the hypothesis that the extent of corpus callosum injury
      indicates the depth of shearing lesions in the central brain structure and
      therefore relates to the clinical severity of diffuse axonal injury. METHODS: A
      simple and objective procedure for semiquantitative analysis of magnetic
      resonance images (MRI)-the maximum signal intensity ratio (MSIR)-was employed
      prospectively in 21 patients with diffuse axonal injury but without apparent
      injury to the ventral pons. All were diagnosed using serial combination MRI scans
      of fluid attenuated inversion recovery (FLAIR) and T2* weighted gradient echo
      imaging during the initial two weeks after the injury. The signal intensity ratio
      between the two regions of interest-the corpus callosum and the normal appearing
      ventral pons-was calculated serially in mid-sagittal and parasagittal FLAIR image
      sections in each patient. The MSIR during the study period was determined as a
      semiquantitative index of corpus callosum injury in each patient. The
      correlations between MSIR and the duration of unconsciousness, Glasgow outcome
      scale at six months, and the presence of apparent midbrain injury were
      investigated. RESULTS: The mean (SD) MSIR value was 1.12 (0.18) at 7.4 (3.1) days
      after the injury (n = 21). MSIR correlated strongly with the duration of
      unconsciousness (n = 19, R(2) = 0.74, p < 0.0001), and was higher in patients
      with both an unfavourable GOS outcome (p = 0.020) and apparent midbrain injury (p
      < 0.001). CONCLUSIONS: MSIR, which is a simple and objective procedure for
      semiquantitative analysis of corpus callosum damage in diffuse axonal injury,
      correlated with clinical severity. A high MSIR value may indicate the presence of
      concomitant midbrain injury.

PMID- 12185161
TI  - Concurrent arterial aneurysms in brain arteriovenous malformations with
      haemorrhagic presentation.
AB  - OBJECTIVE: To assess the effect of concurrent arterial aneurysms on the risk of
      incident haemorrhage from brain arteriovenous malformations (AVMs). METHODS: In a
      cross sectional study, 463 consecutive, prospectively enrolled patients from the
      Columbia AVM Databank were analysed. Concurrent arterial aneurysms on brain
      angiography were classified as feeding artery aneurysms, intranidal aneurysms,
      and aneurysms unrelated to blood flow to the AVM. Clinical presentation
      (diagnostic event) was categorised as intracranial haemorrhage proved by imaging
      or non-haemorrhagic presentation. Univariate and multivariate statistical models
      were applied to test the effect of age, sex, AVM size, venous drainage pattern,
      and the three types of aneurysms on the risk of AVM haemorrhage at initial
      presentation. RESULTS: Arterial aneurysms were found in 117 (25%) patients with
      AVM (54 had feeding artery aneurysms, 21 had intranidal aneurysms, 18 had
      unrelated aneurysms, and 24 had more than one aneurysm type). Intracranial
      haemorrhage was the presenting symptom in 204 (44%) patients with AVM. In the
      univariate model, the relative risk for haemorrhagic AVM presentation was 2.28
      (95% confidence interval (CI) 1.12 to 4.64) for patients with intranidal
      aneurysms and 1.88 (95% CI 1.14 to 3.08) for those with feeding artery aneurysms.
      In the multivariate model an independent effect of feeding artery aneurysms (odds
      ratio 2.11, 95% CI 1.18 to 3.78) on haemorrhagic AVM presentation was found. No
      significant effect was seen for intranidal and unrelated aneurysms. The
      attributable risk of feeding artery aneurysms for incident haemorrhage in
      patients with AVM was 6% (95% CI 1% to 11%). CONCLUSIONS: The findings suggest
      that feeding artery aneurysms are an independent determinant for increased risk
      of incident AVM haemorrhage.

PMID- 12185162
TI  - Dermal microdialysis provides evidence for hypersensitivity to noradrenaline in
      patients with familial dysautonomia.
AB  - OBJECTIVES: To use the technique of dermal microdialysis to examine sensitivity
      of skin vessels to noradrenaline (NA) in patients with familial dysautonomia (FD)
      and in healthy controls. METHODS: In 14 patients with FD and 12 healthy controls,
      plasma extravasation, local laser Doppler blood flow, and skin blanching were
      observed before, during, and after application of 10(-6) M NA through a
      microdialysis membrane, located intradermally in the skin of the lower leg.
      RESULTS: Maximum local vasoconstriction measured by laser Doppler blood flow did
      not differ between patients with FD and controls. In contrast, patients with FD
      had an earlier onset of vasoconstriction (p = 0.02). Moreover, reaction to NA was
      more prominent and prolonged in FD, shown by a larger zone of skin blanching
      around the microdialysis membrane (p < 0.001) and delayed reduction of the
      protein content in the dialysate after termination of NA application (p = 0.03).
      CONCLUSION: These data support the hypothesis that peripheral blood vessels of
      patients with FD show a denervation hypersensitivity to catecholamines. This may
      be one mechanism contributing to the major hypertension that frequently occurs
      during "dysautonomic crises" in FD.

PMID- 12185163
TI  - Thomas Laycock (1812-1876).

PMID- 12185165
TI  - Characteristics of patients with persistent severe disability and medically
      unexplained neurological symptoms: a pilot study.
AB  - This study audited 25 patients (21 female) from Oxfordshire who had been referred
      to either the liaison psychiatry or the neurological disability service between
      1992 and 1998, reported a Barthel activities of daily living index score < 20 or
      a global assessment of functioning score of < or = 30, and had no pathology to
      explain their neurological disability. Levels of motor impairment, disability,
      mood, and cognitive status were assessed using standardised scales, and all
      patients were assigned a psychiatric diagnosis according to the International
      classification of diseases, 10th revision. Of the 25 patients, 13 had a motor
      conversion disorder, 8 had diverse somatoform disorders, and 3 had chronic
      fatigue syndrome. Nine had extensive previous contact with psychiatric services
      and 11 had experienced physical or sexual abuse. In 6 patients cessation of
      repeated self harm was closely associated with the onset of wheelchair use. Seven
      were receiving treatment for depression. The commonest putative diagnoses were
      multiple sclerosis (6) and epilepsy (5). Twelve were unable to walk and 20 owned
      a wheelchair but only 3 had formal care packages. The mean (SD) Barthel score was
      14.1 (3.3) and the mean (SD) Frenchay activity index score was 12.9 (7.5). All
      were unemployed and receiving a disability living allowance, and some had
      benefits of up to pound 1815 a month. This small but significant group of
      disabled patients had a variety of psychiatric and neurological diagnoses and
      used considerable health care resources.

PMID- 12185164
TI  - Six novel connexin32 (GJB1) mutations in X-linked Charcot-Marie-Tooth disease.
AB  - X-linked Charcot-Marie-Tooth disease (CMTX) is a clinically heterogeneous
      hereditary motor and sensory neuropathy with X-linked transmission. Common
      clinical manifestations of CMTX, as in other forms of Charcot-Marie-Tooth disease
      (CMT), are distal muscle wasting and weakness, hyporeflexia, distal sensory
      disturbance, and foot deformities. Motor nerve conduction velocity is reduced. In
      male patients it is often less than 38 m/s in the median nerve (a value often
      used to distinguish between "demyelinating" and "axonal" forms of CMT), but in
      female patients conduction velocity may be faster than this or normal. Mutations
      in the connexin32 (gap junction protein beta 1 (GJB1)) gene are responsible for
      the majority of CMTX cases. This report describes six British CMTX families with
      six novel mutations (four missense, one nonsense, and one frame shift) of the
      GJB1 gene. Affected members in these six families had typical signs of CMT but in
      some affected members of three families there was additional central nervous
      system involvement or deafness in the absence of any other explanation other than
      CMT.

PMID- 12185166
TI  - Typical features of cerebellar ataxic gait.
AB  - BACKGROUND: Although gait disturbance is one of the most pronounced and disabling
      symptoms in cerebellar disease (CD), quantitative studies on this topic are rare.
      OBJECTIVES: To characterise the typical clinical features of cerebellar gait and
      to analyse ataxia quantitatively. METHODS: Twelve patients with various
      cerebellar disorders were compared with 12 age matched controls. Gait was
      analysed on a motor driven treadmill using a three dimensional system. A tandem
      gait paradigm was used to quantify gait ataxia. RESULTS: For normal locomotion, a
      significantly reduced step frequency with a prolonged stance and double limb
      support duration was found in patients with CD. All gait measurements were highly
      variable in CD. Most importantly, balance related gait variables such as step
      width and foot rotation angles were increased in CD, indicating the need for
      stability during locomotion. The tandem gait paradigm showed typical features of
      cerebellar ataxia such as dysmetria, hypometria, hypermetria, and inappropriate
      timing of foot placement. CONCLUSIONS: Typical features of gait in CD are reduced
      cadence with increased balance related variables and an almost normal range of
      motion (with increased variability) in the joints of the lower extremity. The
      tandem gait paradigm accentuates all the features of gait ataxia and is the most
      sensitive clinical test.

PMID- 12185167
TI  - Relation between walking speed and muscle strength is affected by somatosensory
      loss in multiple sclerosis.
AB  - OBJECTIVE: To evaluate the correlation between gait speed and strength in
      multiple sclerosis (MS) with particular regard to patients presenting with
      proprioceptive loss. METHODS: Gait evaluation and isokinetic testing of muscular
      function were performed in 20 patients with unaided gait (expanded disability
      status scale < 6). Patients were separated into two groups in relation to the
      occurrence of somatosensory involvement: pyramidal group (8 patients) and sensory
      pyramidal group (12 patients). Ten healthy subjects of similar age, sex, and
      height constituted a control group to evaluate gait parameters. RESULTS: In the
      whole patient group, gait speed was reduced and strongly related to hamstring
      peak torque but not with quadriceps peak torque. The gait speed and peak torques
      of quadriceps and hamstrings were similar in both groups of patients. However, in
      the patients with proprioceptive loss there was both a strong correlation between
      gait speed and hamstring torque and a significant correlation with quadriceps
      torque. In the pyramidal group there was poor or no correlation. CONCLUSION: In
      patients with undifferentiated MS there is some correlation between gait speed
      and muscle strength. In the case of sensory loss, a higher contribution of both
      flexor and extensors of the lower limbs was observed, suggesting that muscular
      compensation occurred in this situation to maintain gait speed. These results are
      relevant to assess rehabilitation modalities in MS.

PMID- 12185168
TI  - Cecile Vogt (1875-1962).

PMID- 12185170
TI  - Hemiageusia resulting from a cavernous haemangioma in the brain stem.

PMID- 12185169
TI  - Age related shift in the primary sites of involvement in cervical spondylotic
      myelopathy from lower to upper levels.
AB  - Ascending axonal volleys were analysed after epidural stimulation at multiple
      sites along the cervical cord to localise the site of the lesion precisely in
      cervical spondylotic myelopathy. The intraoperative recordings uncovered a single
      site of focal conduction block in 129 of 136 affected patients who underwent
      surgical intervention because of evidence of multilevel compression obtained by
      magnetic resonance imaging. Statistical analyses showed a shift of abnormalities
      from lower to upper cervical levels with advancing age (p < 0.0001). In
      particular, 92% of the oldest group (aged over 70 years) had localised
      dysfunction at C3-4 or C4-5, while 68% of patients aged under 60 years had
      lesions at C5-6 or C6-7.

PMID- 12185171
TI  - Expression of chemokines in cerebrospinal fluid and serum of patients with
      chronic inflammatory demyelinating polyneuropathy.
AB  - Chemokines are likely to contribute to the pathogenesis of chronic inflammatory
      demyelinating polyneuropathy (CIDP), as evidenced by data from experimental
      autoimmune neuritis. The alpha and beta chemokines in the cerebrospinal fluid
      (CSF) and serum from patients with CIDP were analysed using an enzyme linked
      immunosorbent assay. CXCL9, CXCL10, and CCL3 were raised in the CSF in CIDP
      compared with controls and non-demyelinating neuropathies (p < 0.001). Although
      the CSF levels of CCL2 were significantly higher than the serum levels for all
      groups, the difference between groups was not significant. CXCL9, CXCL10, and
      CCL3 may contribute to the pathogenesis of CIDP by recruiting inflammatory T
      cells and monocytes to spinal nerve roots, while CCL2 is likely to play a
      physiological role.

PMID- 12185172
TI  - Tubular aggregate myopathy with abnormal pupils and skeletal deformities.
AB  - A patient is described with a novel syndrome characterised by progressive
      muscular weakness, contractures, pupillary muscle dysfunction, and skeletal
      deformity. The main myopathological feature was an abundance of tubular
      aggregates in both type I and type II muscle fibres. Myopathies in which tubular
      aggregates are the defining feature are rare and either present with progressive
      muscle weakness or exercise induced myalgia. Tubular aggregate myopathy with
      symptomatic smooth muscle dysfunction and skeletal deformities has not been
      described before.

PMID- 12185173
TI  - The legacy of vigabatrin in a regional epilepsy clinic.
AB  - OBJECTIVES: To review all patients who had received vigabatrin at the Walton
      Centre to determine the incidence of visual field defect, seizure outcome if
      vigabatrin had been stopped, and adherence to guidelines on the use of vigabatrin
      in clinical practice. METHODS: Retrospective review of 583 patients prescribed
      vigabatrin at any time between 1989 and 2001 from a regional and satellite
      epilepsy clinic. Data were collected on dose and duration of treatment, results
      of quantitative perimetry, and reasons for, and outcome of, discontinuation.
      RESULTS: The visual fields were abnormal with no alternative cause in 42 of the
      98 tested (43%). There was no clear relation between the cumulative dose of
      vigabatrin received and the occurrence of a visual field abnormality. Fifty
      patients continued taking vigabatrin, and a further 84 were lost to follow up
      while taking vigabatrin. In 75 patients who had stopped vigabatrin due to a
      visual field abnormality or concern over this potential adverse effect, the
      seizure control was no different or had improved in 66 (88%), while it had
      deteriorated in only 7 (9%). CONCLUSIONS: This study confirms the previously
      reported high incidence of asymptomatic visual field defects associated with
      vigabatrin. Many patients taking vigabatrin may not have been counselled about
      the risks, and there are significant cost implications in tracing and assessing
      those patients lost to follow up. Switching over to another antiepileptic drug
      usually does not result in deterioration in seizure control, but in clinical
      practice an individual risk to benefit ratio needs to be taken into
      consideration.

PMID- 12185174
TI  - Impact of early intervention on outcome following mild head injury in adults.
AB  - BACKGROUND: The impact of mild head injury is variable and determinants of
      outcome remain poorly understood. Results of previous intervention studies have
      been mixed. OBJECTIVES: To evaluate the impact on outcome of the provision of
      information, measured in terms of reported symptoms, cognitive performance, and
      psychological adjustment three months postinjury. METHODS: 202 adults with mild
      head injury were studied: 79 were assigned to an intervention group and were
      assessed one week and three months after injury; 123 were assigned to a non
      intervention control group and were seen at three months only. Participants
      completed measures of preinjury psychological adjustment, concurrent life
      stresses, post-concussion symptoms, and tests of attention, speed of information
      processing, and memory. Subjects seen at one week were given an information
      booklet outlining the symptoms associated with mild head injury and suggested
      coping strategies. Those seen only at three months after injury did not receive
      this booklet. RESULTS: Patients in the intervention group who were seen at one
      week and given the information booklet reported fewer symptoms overall and were
      significantly less stressed at three months after the injury. CONCLUSIONS: The
      provision of an information booklet reduces anxiety and reporting of ongoing
      problems.

PMID- 12185175
TI  - Quantitative cardiovascular autonomic function study in Fisher syndrome.
AB  - Quantitative cardiovascular autonomic function tests were performed
      longitudinally in nine patients with Fisher syndrome (FS). Parasympathetic
      autonomic function was evaluated by the Valsalva ratio and RR interval variation
      during rest and deep breathing. Sympathetic autonomic function was evaluate by
      blood pressure responses to sustained handgrip and to active standing. None of
      the patients with FS had clinical signs of autonomic dysfunction during the
      course of their illness. However, autonomic function abnormalities were seen in
      up to 83% of patients with FS. Thus, bedside clinical signs of autonomic
      dysfunctions are inadequate for the assessment of autonomic abnormality compared
      with quantitative autonomic function examination. Most autonomic function tests
      tended to improve after 4-12 weeks. Although parasympathetic and sympathetic
      functions were both involved at the height of FS, parasympathetic fibres were
      less vulnerable than the sympathetic fibres.

PMID- 12185176
TI  - Cerebral Whipple's disease with a stroke-like presentation and cerebrovascular
      pathology.
AB  - Although neurological symptoms are common in Whipple's disease, patients rarely
      have a purely neurological presentation and involvement restricted to the central
      nervous system is uncommon. A 39 year old woman presented with a
      meningoencephalitic illness, which responded to penicillin. Eleven months later
      she developed recurrent stroke-like episodes. Patchy enhancing meningeal,
      cortical, and subcortical lesions thought to be vascular in origin developed
      within nine days of the onset of symptoms. No evidence was found of a
      cardiovascular source of emboli, vasculitis, or thrombophilic condition. A brain
      biopsy showed meningoencephalitic features suspicious of Whipple's disease
      associated with leptomeningeal arterial fibrosis and thrombosis. DNA polymerase
      chain reaction confirmed Tropheryma whippelii in both blood and brain tissue. The
      neurological manifestations of cerebral Whipple's disease are varied and very
      rarely include stroke-like symptoms. The pathogenesis of cerebral infarction in
      Whipple's disease is not well established but arterial fibrosis and endocarditis
      complicated by embolisation have been reported. This case emphasises the
      importance of early brain biopsy in unusual cases of stroke and illustrates the
      clinical utility of polymerase chain reaction to confirm Whipple's disease.

PMID- 12185177
TI  - Neurological presentation of Fabry's disease in a 52 year old man.
AB  - Fabry's disease is an X linked inborn error of metabolism due to deficient
      activity of the lysosomal enzyme alpha galactosidase A. Previously unrecognised
      Fabry's disease presenting in a 52 year old man being investigated for
      progressive dysarthria and ataxia is discussed. Brain magnetic resonance imaging
      suggested the presence of small vessel disease but skin biopsy (done to exclude
      cerebral autosomal dominant arteriopathy with subcortical infarcts and
      leucencephalopathy) showed typical changes of Fabry's disease. This diagnosis was
      confirmed by subsequent enzyme assays. The authors contend that Fabry's disease
      should be excluded, at least on clinical grounds, in patients with otherwise
      unexplained cerebrovascular disease.

PMID- 12185178
TI  - An unusual case of Behcet's disease presenting with bilateral internal carotid
      artery occlusion.

PMID- 12185179
TI  - Neuromyotonia and myasthenia gravis without thymoma.

PMID- 12185180
TI  - Miller-Fisher syndrome and Hodgkin's disease.

PMID- 12185181
TI  - Acute attacks and brain stem signs in a patient with glutamic acid decarboxylase
      autoantibodies.

PMID- 12185182
TI  - High concentrations of sVCAM-1 and sICAM-1 in the cerebrospinal fluid of patients
      with intracerebral haemorrhage are associated with poor outcome.

PMID- 12185183
TI  - Ondine's curse in a woman with Leber's hereditary optic neuropathy.

PMID- 12185184
TI  - Risk of relapse of Guillain-Barre syndrome or chronic inflammatory demyelinating
      polyradiculoneuropathy following immunisation.

PMID- 12185185
TI  - Hypoglycaemia induced by phenytoin treatment for partial status epilepticus.

PMID- 12185186
TI  - Meta-analysis of alpha synuclein/ NACP polymorphism in Parkinson's disease in
      Japan.

PMID- 12185187
TI  - Patent foramen ovale, cerebrovascular risk, and complement.

PMID- 12185188
TI  - Mexiletine on segmental hyperhidrosis.

PMID- 12185189
TI  - Genotype predisposition to leukoaraiosis.

PMID- 12185190
TI  - Demyelination in the brain as a paraneoplastic disorder: candidates include some
      cases of seminoma and central nervous system lymphoma.

PMID- 12185192
TI  - Distribution patterns of ornithine decarboxylase in cells and tissues: facts,
      problems, and postulates.
AB  - Ornithine decarboxylase (ODC) is a key enzyme in polyamine biosynthesis.
      Increased polyamine levels are required for growth, differentiation, and
      transformation of cells. In situ detection of ODC in cells and tissues has been
      performed with biochemical, enzyme cytochemical, immunocytochemical, and in situ
      hybridization techniques. Different localization patterns at the cellular level
      have been described, depending on the type of cells or tissues studied. These
      patterns varied from exclusively cytoplasmic to both cytoplasmic and nuclear.
      These discrepancies can be partially explained by the (lack of) sensitivity
      and/or specificity of the methods used, but it is more likely that (sub)cellular
      localization of ODC is cell type-specific and/or depends on the physiological
      status (growth, differentiation, malignant transformation, apoptosis) of cells.
      Intracellular translocation of ODC may be a prerequisite for its regulation and
      function.

PMID- 12185193
TI  - HSP70 constitutive expression in rat central nervous system from postnatal
      development to maturity.
AB  - We studied the level of the basal (constitutive) HSP70 expression (inducible and
      constitutive forms) in the central nervous system (CNS) of male and female rats
      from the postnatal period to maturity. HSP70 levels were analyzed by
      immunoblotting in five different areas (cortex, hippocampus, hypothalamus,
      cerebellum, and spinal cord). The highest levels of HSP70 were found in juvenile
      rats and decreased progressively until reaching baseline levels between 2 and 4
      months. A slight and nonsignificant increase in aged (2-year-old) rats compared
      with adult subjects was observed in some cerebral areas (cerebral cortex,
      hippocampus, and cerebellum). In the first weeks of postnatal development, HSP70
      immunoreactivity was distributed throughout CNS sections and no specific
      immunopositive cells could be clearly determined. In adult animals, strong
      immunostaining was observed in some large neurons (Purkinje neurons and
      mesencephalic and spinal cord motor neurons), some perivascular and subpial
      astrocytes, and ependymocytes. Immunoelectron microscopy revealed that HSP70 in
      these cells is located in the perinuclear area and in mitochondria, rough
      endoplasmic reticulum, and microtubules. In neurons, strong immunolabeling was
      also observed in synaptic membranes. The postnatal time course of HSP70 levels
      and the location and size of HSP70-immunopositive cells suggest that HSP70
      constitutively expressed in the rat CNS may be mainly determined by the degree of
      development and metabolic activity of the neural cells.

PMID- 12185194
TI  - CD26/DPPIV signal transduction function, but not proteolytic activity, is
      directly related to its expression level on human Th1 and Th2 cell lines as
      detected with living cell cytochemistry.
AB  - CD26/DPPIV is a cell surface glycoprotein that functions both in signal
      transduction and as a proteolytic enzyme, dipeptidyl peptidase IV (DPPIV). To
      investigate how two separate functions of one molecule are regulated, we analyzed
      CD26 protein expression and DPPIV enzyme activity on living human T-helper 1
      (Th1) and Th2 cells that express different levels of CD26/DPPIV. DPPIV activity
      was specifically determined with the synthetic fluorogenic substrate ala-pro
      cresyl violet and CD26 protein expression was demonstrated with an FITC
      conjugated CD26-specific antibody. Fluorescence of liberated cresyl violet (red)
      and FITC (green) was detected simultaneously on living T-cells using flow
      cytometry and spectrofluorometry. Th1 cells expressed three- to sixfold more CD26
      protein than Th2 cells. The signal transduction function of the CD26/DPPIV
      complex, tested by measuring its co-stimulatory potential for proliferation, was
      directly related to the amount of CD26 protein at the cell surface. However,
      DPPIV activity was similar in both cell populations at physiological substrate
      concentrations because of differences in K(m) and V(max) values of DPPIV on Th1
      and Th2 cells. Western blotting and zymography of Th1 and Th2 whole-cell lysates
      demonstrated similar patterns. This study shows that two functions of one
      molecule can be controlled differentially.

PMID- 12185195
TI  - Distribution of sialoglycoconjugates in the rat cerebellum and its change with
      aging.
AB  - We examined the distribution of sialoglycoconjugates in the cerebellum of 9-week
      old and 30-month-old rats using light microscopy and electron microscopy in
      combination with two lectins, Maackia amurensis lectin (MAL) for Sia(alpha)2-3Gal
      and Sambucus sieboldiana agglutinin (SSA) for Sia(alpha)2-6Gal. Each lectin
      showed characteristic staining patterns. In young adult rats, MAL stained a
      strongly granular layer, a weakly molecular layer, and the medullary lamina,
      while SSA more strongly stained the medullary lamina than the molecular and
      granular layers. After aging, different staining patterns were obtained. Intense
      SSA reactivity was observed in the granular layer and intense MAL reactivity was
      observed in the medullary lamina of the aged groups. The reactivity of Purkinje
      cells with MAL was downregulated in the aged rats. These results indicated that
      Sia(alpha)2-3Gal and Sia(alpha)2-6Gal were expressed in distinct regions of the
      rat cerebellum and that their expression patterns changed in the aged brain.

PMID- 12185196
TI  - Interaction of protein phosphatase 1 delta with nucleolin in human osteoblastic
      cells.
AB  - We examined the expression and cytolocalization of the protein phosphatase type 1
      delta (PP1delta) isoform and nucleolin in human osteoblastic MG63 and Saos-2
      cells. Cellular fractionation of MG63 cells was done and protein was prepared
      from each fraction. Anti-nucleolin antibody interacted with the 100- and 95-kD
      proteins present in the whole-cell lysate. The 100-kD protein was detected in
      nuclear and nucleolar fractions. The 95-kD protein was detected in cytosolic and
      nucleoplasmic fractions. PP1delta and nucleolin were co-localized in the
      nucleolus in MG63 and Saos-2 cells revealed by an immunofluorescence method.
      PP1delta and nucleolin were also co-immunoprecipitated with anti-nucleolin and
      anti-PP1delta antibodies. In the actinomycin D-treated cells, the subcellular
      localization of PP1delta and nucleolin was changed. Expression of PP1delta was
      upregulated with actinomycin D treatment. The level of 100-kD protein did not
      change in the actinomycin D-treated cells. However, the level of the 95-kD band
      increased with actinomycin D treatment. These results indicate that PP1delta was
      associated with nucleolin in the nucleolus of MG63 and Saos-2 cells and that
      nucleolin is a possible candidate substrate for PP1delta.

PMID- 12185197
TI  - CD9 expression in solid non-neuroepithelial tumors and infiltrative astrocytic
      tumors.
AB  - The tetraspan membrane protein CD9 is normally expressed in the mature myelin
      sheath and is believed to suppress the metastatic potential of certain human
      tumors. In this study we identified CD9 in a variety of brain tumors by
      immunohistochemical (IHC) and immunoblotting analyses. We examined 96 tumor
      samples and three glioma cell lines in addition to a murine brain tumor model of
      transplanted glioma cells in CD9-deficient mice and control mice. CD9 was
      expressed not only in solid non-neuroepithelial tumors but also in infiltrative
      malignant neuroepithelial tumors. Among the neuroepithelial tumors, high-grade
      astrocytic tumors, including glioblastomas and anaplastic astrocytomas, showed
      higher immunoreactivity than low-grade cerebral astrocytomas. Thus, CD9
      expression in astrocytic tumors correlated with their malignancy. In the murine
      brain tumor model, transplanted glioma cells were shown to grow and spread
      through myelinated areas irrespective of the presence or absence of CD9
      expression in the recipient's brain. These results indicate that the CD9
      expression of astrocytic tumors plays a significant role in the malignancy
      independent of CD9 expression in the surrounding tissue. This might be explained
      by the observation that the CD9 molecule is associated with a mitogenic factor,
      membrane-anchored heparin-binding epidermal growth factor, which is known to be
      upregulated in malignant gliomas.

PMID- 12185198
TI  - Spectrally resolved microscopy of GFP trafficking.
AB  - Folding and chromophore cyclization-oxidation processes of green and cyan
      fluorescent fusion proteins (GFP and CFP) in subcellular microenvironments of
      transfected C6 glioma cells were studied by multipixel spectrally resolved
      microscopy (SRM). Discrete time-dependent spectral transitions were characterized
      during protein folding and chromophore maturation in the cytosol, nucleus,
      mitochondria, endoplasmic reticulum (ER), and Golgi. Spectral similarity mapping
      of fluorophore transition phases demarcated spatio-temporal fluorescence
      correlation at a subcellular level. Folding stages were characterized by a
      transition from red-shifted spectral populations in the time interval of 7-10 hr
      after transfection to a fully matured fluorophore emitting typical GFP or CFP
      fluorescence after 10-15 hr. The nascent protein revealed an initial focal
      accumulation in cytosol emitting in the range of 580-680 nm. After 10 hr, mixed
      pixel population spectra were measured and at 15 hr GFP was visualized in the
      cytoplasm by its specific spectral fingerprints with maxima at 545 nm. For
      nucleus- and mitochondrion-targeted CFPs, the mature conformer was discovered
      only in its final destination, whereas intermediate steps of fluorophore
      synthesis (at 10 hr) were found in the cytoplasm. Enhanced fluorescence
      maturation was manifested only by the ER-Golgi-targeted CFP after 10 hr post
      transfection by spectral imaging. Moreover, only remnants of initial intermediate
      fluorescent pixels were localized externally to the Golgi framework at 15 hr. SRM
      assessed the competence of ER-Golgi to maintain efficient CFP folding in
      comparison to the rest of the cellular compartments.

PMID- 12185199
TI  - Endocytosis of anti-CCK-B/gastrin receptor antibody and effect on hepatoma cell
      lines.
AB  - Immunotherapy has considerable potential in the treatment of cancer. Here we
      report on the uptake of an antibody raised against the CCK-B/Gastrin receptor
      (CCK-BR) by liver embryonic and liver tumor cell lines. In all five cell lines
      studied, expression of CCK-BR and uptake of labeled anti-CCK-BR antibody was
      observed. The labeled anti-CCK-BR antibody was localized in both the cytoplasm
      and nucleus of cells. In addition, we found a coincidence between the uptake of
      the labeled antibody by cells and the occurrence of apoptosis (cell death). The
      results suggest that antibodies directed against CCK-BR have potential for
      targeting and possibly destroying tumor cells bearing the receptor.

PMID- 12185200
TI  - Detection of viral infection and gene expression in clinical tissue specimens
      using branched DNA (bDNA) in situ hybridization.
AB  - In situ hybridization (ISH) methods for detection of nucleic acid sequences have
      proved especially powerful for revealing genetic markers and gene expression in a
      morphological context. Although target and signal amplification technologies have
      enabled researchers to detect relatively low-abundance molecules in cell
      extracts, the sensitive detection of nucleic acid sequences in tissue specimens
      has proved more challenging. We recently reported the development of a branched
      DNA (bDNA) ISH method for detection of DNA and mRNA in whole cells. Based on bDNA
      signal amplification technology, bDNA ISH is highly sensitive and can detect one
      or two copies of DNA per cell. In this study we evaluated bDNA ISH for detection
      of nucleic acid sequences in tissue specimens. Using normal and human
      papillomavirus (HPV)-infected cervical biopsy specimens, we explored the cell
      type-specific distribution of HPV DNA and mRNA by bDNA ISH. We found that bDNA
      ISH allowed rapid, sensitive detection of nucleic acids with high specificity
      while preserving tissue morphology. As an adjunct to conventional histopathology,
      bDNA ISH may improve diagnostic accuracy and prognosis for viral and neoplastic
      diseases.

PMID- 12185201
TI  - Expression of alternatively spliced RNA transcripts of amelogenin gene exons 8
      and 9 and its end products in the rat incisor.
AB  - In addition to seven known exons of the amelogenin gene, recent studies have
      identified two exons downstream of amelogenin exon 7 in genomic DNA of mouse and
      rat. Here the spatial and temporal expression of mRNAs and of the translated
      proteins derived from alternative splicing of the amelogenin gene ending with
      exon 8 and exon 9 were examined by in situ hybridization (ISH) and
      immunohistochemistry (IHC). RNA signals for exons 8 and 9 were expressed in the
      ameloblast layer extending from early presecretory to postsecretory transitional
      stages of amelogenesis. IHC of amelogenin proteins that include sequences encoded
      by these exons demonstrated identical localization of these proteins in the
      ameloblast layer corresponding to RNA signals identified by ISH. There was
      intense immunostaining of the enamel matrix secreted by these cells. Western
      blotting analysis of rat enamel proteins revealed three distinct protein bands
      with sequences encoded by the new exons. These data confirmed the existence of
      the transcripts of alternatively spliced mRNAs coding for exons 8 and 9 of the
      amelogenin gene in rat tooth germs and suggest that the translated proteins
      contribute to the heterogeneity of amelogenins and have some significant roles in
      enamel formation and mineralization.

PMID- 12185202
TI  - Methacarn fixation for genomic DNA analysis in microdissected, paraffin-embedded
      tissue specimens.
AB  - We recently found methacarn to be a versatile fixative for analysis of RNA and
      protein applicable for microdissected specimens from paraffin-embedded tissue
      (PET). In this study we investigated the performance of methacarn for genomic DNA
      analysis using microdissected rat tissues. We found that extensive portions of
      DNA up to 2.8 kb could be amplified by nested PCR using DNA templates extracted
      by a simple and rapid extraction procedure from a 1 x 1-mm area of cerebral
      cortex of a 10-microm-thick section. By nested PCR, a 522-bp fragment from a
      single cell could be amplified in 20% of cresyl violet-stained Purkinje cells,
      and the minimal number of cells required, as estimated using hippocampal neurons,
      was on the order of 10-20. Although tissue staining with hematoxylin and eosin
      affected the PCR, amplification of a 522-bp fragment was successful, with 150-270
      cells by 35 cycles of single-step PCR. Immunostaining resulted in a substantial
      decrease of yield and degradation of extracted DNA. However, even after
      immunostaining, a 184-bp DNA fragment could be amplified with 150-270 cells by 35
      cycles of PCR. The results thus demonstrate the superior performance of methacarn
      to that reported with formalin in genomic DNA analysis using microdissected PET
      specimens.

PMID- 12185203
TI  - Human kallikrein 10 expression in normal tissues by immunohistochemistry.
AB  - The normal epithelial cell-specific 1 (NES1) gene (official name kallikrein gene
      10, KLK10) was recently cloned and encodes for a putative secreted serine
      protease (human kallikrein 10, hK10). Several studies have confirmed that hK10
      shares many similarities with the other kallikrein members at the DNA, mRNA, and
      protein levels. The enzyme was found in biological fluids, tissue extracts, and
      serum. Here we report the first detailed immunohistochemical (IHC) localization
      of hK10 in normal human tissues. We used the streptavidin-biotin method with two
      hK10-specific antibodies, a polyclonal rabbit and a monoclonal mouse antibody,
      developed in house. We analyzed 184 paraffin blocks from archival, current, and
      autopsy material, prepared from almost every normal human tissue. The staining
      pattern, the distribution of the immunostaining, and its intensity were studied
      in detail. Previously, we reported the expression of another novel human
      kallikrein, hK6, by using similar techniques. The IHC expression of hK10 was
      generally cytoplasmic and not organ-specific. A variety of normal human tissues
      expressed the protein. Glandular epithelia constituted the main immunoexpression
      sites, with representative organs being the breast, prostate, kidney, epididymis,
      endometrium, fallopian tubes, gastrointestinal tract, bronchus, salivary glands,
      bile ducts, and gallbladder. The choroid plexus epithelium, the peripheral
      nerves, and some neuroendocrine organs (including the islets of Langerhans, cells
      of the adenohypophysis, the adrenal medulla, and Leydig cells) expressed the
      protein strongly and diffusely. The spermatic epithelium of the testis expressed
      the protein moderately. A characteristic immunostaining was observed in Hassall's
      corpuscles of the thymus, oxyphilic cells of the thyroid and parathyroid glands,
      and chondrocytes. Comparing these results with those of hK6, we observed that
      both kallikreins had a similar IHC expression pattern.

PMID- 12185204
TI  - Localization of the induced metallothionein and DNA damage in rat kidney after
      gold injection.
AB  - To clarify the relationships between DNA damage and Cu-MT and between DNA damage
      and Cu in kidneys of rats injected with Au, we examined the histochemical
      localization of DNA damage, metallothionein (MT), and the accumulated Cu in the
      kidneys of rats injected with Au, Cu, or Cu-MT. The immunoreactivity of MT was
      observed predominantly in the outer stripe of the outer medulla and the inner
      cortex of the Au-injected rat, and the signals of terminal deoxynucleotidyl
      transferase (TdT)-mediated dUTP-biotin nick end labeling (TUNEL) were observed in
      the cortex. Cu detected by Timm's method was mainly distributed in the cortex of
      the Au-injected rat. These results indicated that DNA damage could be caused by
      free Cu in the cortex but not by the Cu bound to MT in the outer stripe of the
      outer medulla. This consideration was supported by the data from rats injected
      with Cu and Cu-MT. Furthermore, we determined the Cu contents in three fractions
      (cytosol, organelle, and precipitate-containing nuclei) of the kidneys.
      Interestingly, most of the Cu content in the kidney of the rat injected with Au
      or Cu-MT was detected in the cytosol, whereas most of the Cu content in the
      kidney of the rat injected with Cu was detected in the nuclei-containing
      precipitate. These findings suggest that the DNA damage in the kidneys of rats
      injected with Au may be associated with Cu-binding proteins but not with Cu-MT.

PMID- 12185205
TI  - Immunohistochemical localization of the nucleosome-binding protein HMGN3 in mouse
      brain.
AB  - HMGN3 (Trip7) is a member of the high-mobility group N (HMGN) nucleosome-binding
      protein family, which binds specifically to nucleosomes, reduces the compactness
      of the chromatin fiber, and enhances transcription from chromatin templates. By
      Western blotting and Northern blotting analysis, we showed that HMGN3 is
      expressed in a tissue-specific manner, with the strongest expression in mouse
      brain. Here we analyzed the expression of HMGN3 in various regions of the mouse
      brain by histological techniques. Enhanced expression of HMGN3 was observed in
      the lateral olfactory tract, anterior commissure, corpus callosum, internal
      capsule, fornix, stria medullans, optic tract, and axon bundles. The expression
      patterns of HMGN3 in the mouse brain was significantly different from that of the
      related protein HMGN2 and was very similar to that of the glial fibrillary acidic
      protein (GFAP). We suggest that HMGN3 might play a role in astrocyte function.

PMID- 12185206
TI  - Annexin 6 immunoreactivity in select cell populations in the rat brain.
AB  - We examined the distribution of annexin 6 (ANX6) in rat brain with
      immunohistochemistry (IHC). Several neuronal cell populations were intensely
      labeled with the ANX6 monoclonal antibody (MAb), including layer 5 of neocortex,
      the lateral septum, the lateral hypothalamic area, the red nucleus, and the
      Purkinje cell layer in cerebellum. Neuronal immunolabeling was localized to the
      nucleus and the cytosol. Darkly stained ANX6-immunoreactive glia, with the
      morphology characteristic of astrocytes, were abundant in the hippocampus,
      substantia nigra reticulata, and cerebellum. Evidence suggests that ANX6 may
      function in neuronal and glial calcium-dependent processes.

PMID- 12185207
TI  - Copper as an essential nutrient and nicotinic acid as the anti-black tongue
      (pellagra) factor: the work of Conrad Arnold Elvehjem.

PMID- 12185208
TI  - Rapid mapping of protein structure, interactions, and ligand binding by
      misincorporation proton-alkyl exchange.
AB  - Understanding protein conformation, interactions, and ligand binding is essential
      to all biological inquiry. We report a novel biochemical technique, called
      misincorporation proton-alkyl exchange (MPAX), that can be used to footprint
      protein structure at single amino acid resolution. MPAX exploits translational
      misincorporation of cysteine residues to generate probes for physical analysis.
      We apply MPAX to the triosephosphate isomerase (beta/alpha)(8) barrel, accurately
      determining its substrate-binding site, a protein-protein interaction surface,
      the solvent-accessible protein surface, and the stability of the barrel. Because
      MPAX requires only microgram quantities of material and is not limited by protein
      size, it is ideally suited for proteins not amenable to conventional structural
      methods, such as membrane proteins, partially folded or insoluble proteins, and
      large protein complexes.

PMID- 12185209
TI  - Psychological aspects of natural language. use: our words, our selves.
AB  - The words people use in their daily lives can reveal important aspects of their
      social and psychological worlds. With advances in computer technology, text
      analysis allows researchers to reliably and quickly assess features of what
      people say as well as subtleties in their linguistic styles. Following a brief
      review of several text analysis programs, we summarize some of the evidence that
      links natural word use to personality, social and situational fluctuations, and
      psychological interventions. Of particular interest are findings that point to
      the psychological value of studying particles-parts of speech that include
      pronouns, articles, prepositions, conjunctives, and auxiliary verbs. Particles,
      which serve as the glue that holds nouns and regular verbs together, can serve as
      markers of emotional state, social identity, and cognitive styles.

PMID- 12185210
TI  - Psychotherapy for children and adolescents.
AB  - Child and adolescent therapy has progressed considerably, as reflected in the
      number of controlled studies, their methodological quality, and identification of
      evidence-based treatments. Treatments with strong evidence in their behalf are
      used for several clinical problems. Despite the progress, several key areas have
      been neglected in research and this has greatly limited what we know about
      treatment. Prominent among these areas of neglect is research on the mechanisms
      of change, the moderators of treatment outcome, and the generality of research
      findings to the conditions of clinical practice. This article highlights
      progress, characteristics, and limitations of current therapy research. In
      addition, a research plan is offered to advance research by (a) understanding the
      mechanisms or processes through which therapeutic change occurs, (b) drawing on
      developmental psychopathology research to inform treatment, (c) expanding the
      range of questions that guide treatment research and the range of outcome domains
      on which treatment conclusions are based, and (d) monitoring progress to ensure
      that critical questions about treatment are addressed.

PMID- 12185211
TI  - Addiction.
AB  - The development of addiction involves a transition from casual to compulsive
      patterns of drug use. This transition to addiction is accompanied by many drug
      induced changes in the brain and associated changes in psychological functions.
      In this article we present a critical analysis of the major theoretical
      explanations of how drug-induced alterations in psychological function might
      cause a transition to addiction. These include: (a) the traditional hedonic view
      that drug pleasure and subsequent unpleasant withdrawal symptoms are the chief
      causes of addiction; (b) the view that addiction is due to aberrant learning,
      especially the development of strong stimulus-response habits; (c) our incentive
      sensitization view, which suggests that sensitization of a neural system that
      attributes incentive salience causes compulsive motivation or "wanting" to take
      addictive drugs; and (d) the idea that dysfunction of frontal cortical systems,
      which normally regulate decision making and inhibitory control over behavior,
      leads to impaired judgment and impulsivity in addicts.

PMID- 12185212
TI  - Biology, context, and developmental inquiry.
AB  - This chapter summarizes some of the conceptual changes in developmental research
      over the last half-century. These advances include an acknowledgment of the role
      of maturation; also recognized have been the need for positing distinct
      psychological structures, the influence of temperament, the malleability of the
      infant, the role of the local context, and the dynamic nature of the categories
      describing human psychological types.

PMID- 12185213
TI  - Chronic unexplained fatigue.

PMID- 12185214
TI  - Humour and love: the origination of clown therapy.

PMID- 12185215
TI  - Use of bacille Calmette-Guerin in superficial bladder cancer.
AB  - Intravesical bacille Calmette-Guerin (BCG) has been used by urologists for
      several years after its first reported use as a cancer therapy in the 1930s.
      Morales in 1976 described the usage of BCG as a once weekly intravesical
      instillation for six weeks; this is a treatment regimen that still exists today.
      Its success as a treatment depends on it being used appropriately. It is
      employed: (1) to treat carcinoma in situ or occasionally residual papillary
      tumours; (2) to reduce the number and frequency of recurrent high grade
      superficial tumours; and (3) to prevent disease progression (although this
      remains a controversial point, on which there is no consensus view).
      Unfortunately, the more widespread use of BCG is often limited due its high side
      effect profile. Present research is directed towards reducing its side effect
      profile, improving its efficacy, and understanding its exact mechanism of action,
      which is not fully understood.

PMID- 12185216
TI  - Oral candidiasis.
AB  - Oral candidiasis is a common opportunistic infection of the oral cavity caused by
      an overgrowth of Candida species, the commonest being Candida albicans. The
      incidence varies depending on age and certain predisposing factors. There are
      three broad groupings consisting of acute candidiasis, chronic candidiasis, and
      angular cheilitis. Risk factors include impaired salivary gland function, drugs,
      dentures, high carbohydrate diet, and extremes of life, smoking, diabetes
      mellitus, Cushing's syndrome, malignancies, and immunosuppressive conditions.
      Management involves taking a history, an examination, and appropriate antifungal
      treatment with a few requiring samples to be taken for laboratory analysis. In
      certain high risk groups antifungal prophylaxis reduces the incidence and
      severity of infections. The prognosis is good in the great majority of cases.

PMID- 12185217
TI  - Multiple sclerosis and pregnancy.
AB  - Multiple sclerosis causes disability in young adults and, like most autoimmune
      diseases, affects women more commonly than men. The disease can therefore present
      at a time when many have, or are considering, starting a family. The effect of
      pregnancy on the outcome of multiple sclerosis is reviewed and the management of
      pregnant women who have multiple sclerosis is discussed.

PMID- 12185218
TI  - Acid suppression in gastro-oesophageal reflux disease: Why? How? How much and
      when?
AB  - For patients with suboptimal relief from lifestyle modifications, acid
      suppressive therapy remains a cornerstone of treatment for gastro-oesophageal
      reflux disease (GORD). While a great deal of attention is focused on
      complications of GORD, adequate symptom relief remains an important and practical
      therapeutic goal. Adequate symptom relief is an achievable and easily measurable
      endpoint that both restores quality of life and prevents many potential
      complications.

PMID- 12185219
TI  - Congenital scoliosis in a neonate: can a neonatologist ignore it?
AB  - The frequency of diagnosis of congenital scoliosis in the neonatal period is
      expected to rise given the increasing survival of high risk neonates in the
      surfactant era and their frequent exposure to x rays. Considering its significant
      long term implications a neonatologist cannot afford to ignore the diagnosis of
      congenital scoliosis in a neonate as close surveillance, early detection, and
      treatment may prevent/minimise the wide spectrum of potentially serious
      deformities that can affect the developing spine. The review provides general
      guidelines to help the neonatologists in counselling the parents and in planning
      the multidisciplinary follow up for management of congenital scoliosis.

PMID- 12185220
TI  - Superior lumbar hernia of Grynfellt.

PMID- 12185221
TI  - Management of colorectal cancer.
AB  - Colorectal cancer is the second most common cause of cancer death in the UK.
      Prompt investigation of suspicious symptoms is important, but there is increasing
      evidence that screening for the disease can produce significant reductions in
      mortality. High quality surgery is of paramount importance in achieving good
      outcomes, particularly in rectal cancer, but adjuvant radiotherapy and
      chemotherapy have important parts to play. The treatment of advanced disease is
      still essentially palliative, although surgery for limited hepatic metastases may
      be curative in a small proportion of patients.

PMID- 12185223
TI  - Patient recall of medication details in the outpatient clinic. Audit and
      assessment of the value of printed instructions requesting patients to bring
      medications to clinic.
AB  - OBJECTIVE: There is no ambiguity when a patient presents their medications in the
      correct packaging during a consultation and declares, "this is what I am taking,
      doctor, I take this many, at this time". The aim of this study was to establish
      the prevalence of consultations in which patients attend both "empty handed" and
      unsure of their treatment. A re-evaluation was made after a simple intervention.
      DESIGN: Prospective cross sectional study with subsequent intervention and re
      evaluation based on patient completed questionnaire. SETTING: University hospital
      cardiology outpatient department. PATIENTS: Consecutive patients arriving at
      clinic reception desks. RESULTS: Altogether 774 of 857 patients were receiving
      treatment; 15% attended with their tablets and 28% provided a note of their
      medication in some form; 40% attended empty handed but confident they could
      recall all aspects of their treatment from memory; 17% attended empty handed and
      unsure of their treatment. INTERVENTION: Clinic appointment cards were stamped
      with the request PLEASE BRING YOUR MEDICATIONS WITH YOU TO THE CARDIOLOGY CLINIC.
      A second unrelated cohort of patients was then surveyed in an identical manner,
      nine months later. Of these, 329 of 376 patients were receiving medication. Those
      attending with their tablets in hand now accounted for 78% rather than 15%
      (chi(2)=423, df=2, p<0.001). The group unsure of their treatment, but attending
      empty handed, fell from 17% to 2%. CONCLUSIONS: Reprinted appointment cards are
      highly successful in encouraging patients to attend with their tablets. This
      provides reliable information for decision making.

PMID- 12185224
TI  - Elbow fistulas using autogeneous vein: patency rates and results of revision.
AB  - BACKGROUND: The provision and maintenance of vascular access remains a major cost
      to end stage renal failure programmes. There are few reports regarding the
      surgical revision of the failing native elbow arteriovenous fistula (AVF).
      PATIENTS AND METHODS: A retrospective case note review was performed on all
      patients identified from the hospital vascular access database as having
      undergone construction of an autogeneous vein elbow AVF. Over a seven year period
      282 autogeneous vein AVFs were fashioned in 232 patients using the brachial
      artery as the in-flow conduit. Of these 208 were brachiocephalic fistulas, or a
      variant thereof, and 74 were fashioned using the transposed autologous basilic
      vein (136 male: 96 female; median age 60 years, range 14-94 years). RESULTS: Of
      282 elbow fistulas 197 were successfully used for dialysis (70%). Cumulative
      primary patency of elbow fistulas using autogeneous vein in this series was 68%,
      54%, and 44% at one, two, and three years respectively. A further 34 revision
      procedures were performed on 28 fistulas to maintain fistula function, and
      cumulative secondary patency after surgical revision was 75%, 60%, and 46% at
      one, two, and three years. Overall 21 out of 34 procedures (62%) successfully
      restored fistula function and cumulative primary patency of the revised fistulas
      was 56% at one year. Eighteen AVFs (brachiocephalic, n=12; autologous basilar
      vein, n=6) required revision for access dysfunction secondary to a short stenoses
      within 4 cm of the arteriovenous anastomoses. Of these 18 AVFs eight were revised
      by excision of the stenosed segment and either primary anastomoses of the two cut
      ends of arterialised vein or reanastomoses of the proximal venous limb proximally
      on the brachial artery. In another nine fistulas the excised segment was replaced
      with a short interposition graft (polytetrafluoroethylene, n=7; native basilic
      vein, n=1; bovine carotid artery, n=1). One fistula with postanastomotic stenoses
      and a more proximal needle site stenoses was revised using two vein patches.
      Overall 100% were patent at 24 hours, 13 provided successful dialysis (72%), and
      cumulative primary patency was 67% and 50% at six months and one year
      respectively. CONCLUSIONS: Successful surgical revision of failing native elbow
      fistulas can restore patency and improve cumulative secondary patency with
      potential benefits in terms of patient morbidity and mortality. These results
      compare favourably to published patency rates after fistula salvage using
      interventional radiological techniques.

PMID- 12185226
TI  - Unusual cardiac manifestation of hypereosinophilic syndrome.
AB  - Hypereosinophilic syndrome was diagnosed in a 14 year old girl who presented with
      recurrent syncope. An ambulatory electrocardiogram revealed intermittent type 2
      second degree left atrioventricular (AV) block. Focal thinning of the
      interventricular septum was noted on echocardiography, contrary to the commoner
      finding of regional ventricular wall thickening among patients with
      hypereosinophilic syndrome. High grade AV block as a manifestation of
      hypereosinophilic syndrome is rare and focal thinning of the left ventricle as a
      manifestation of the syndrome has not been described earlier.

PMID- 12185225
TI  - Iatrogenic causes of falls in hospitalised elderly patients: a case-control
      study.
AB  - OBJECTIVE: To explore risk factors associated with falls and to evaluate a
      strategy used by nurses to predict and prevent falls in a hospitalised cohort of
      elderly patients. DESIGN: A case-control study of risk factors for falls in
      hospital. SETTING: A district general hospital in the UK. SUBJECTS: Altogether
      181 patients in an acute integrated medical unit who had fallen were matched for
      age with 181 patients in the next bed who had not fallen. RESULTS: It was found
      that 46% (84 of 181) of the fallers were taking one or more benzodiazepines
      compared with 27% (48 of 181) of the control patients (p<0.001). More fallers 20%
      (34 of 181) had their benzodiazepines prescribed during their current admission
      compared with 7% (13 of 181) of the control patients (p<0.001). Temazepam was the
      main benzodiazepine used by over 95% of cases and controls. Overall 25% (45 of
      181) of the fallers had fallen before during the current admission. The logistic
      regression analysis showed that only a previous fall, benzodiazepine intake, and
      the need for maximum assistance were significant predictors of falling in
      hospital, odds ratios were 5.6 (95% confidence interval (CI) 2.7 to 11.6), 2.3
      (95% CI 1.4 to 3.7), and 3.1 (95% CI 1.9 to 5.2) respectively. Most fallers had
      been identified at risk of falling (125; 69%) by ward staff and in 113 (90%) of
      those preventive measures had been undertaken. Falls were least likely to occur
      during visiting hours with a peak incidence during night-time. CONCLUSION: There
      is a need for evidenced based successful fall prevention strategies but our study
      also reinforces an urgent public health message that an alternative to
      benzodiazepines should be sought for night sedation for older patients.

PMID- 12185227
TI  - Multifocal cardiac leiomyosarcoma. Diagnosis and surveillance by transoesophageal
      echocardiography and contrast enhanced cardiovascular magnetic resonance.
AB  - Primary cardiac sarcomas are rare and typically undergo aggressive local spread.
      There is no reliable definitive treatment, although radical surgical resection
      can provide palliation in the medium term. A case of a pleomorphic leiomyosarcoma
      with dramatic images is presented. The relative usefulness of transoesophageal
      echocardiography and cardiovascular magnetic resonance imaging to define the
      extent of tumour involvement, allowing planning of treatment, is demonstrated.

PMID- 12185228
TI  - Idiopathic heterotopic ossification in the intensive care setting.
AB  - Heterotopic ossification is characterised by the periarticular deposition of
      ectopic bone. It typically occurs after trauma, neurogenic injury, or congenital
      causes. Idiopathic heterotopic ossification has been rarely reported. A patient
      who developed idiopathic heterotopic ossification in the intensive care unit
      without any known predisposing conditions is presented.

PMID- 12185229
TI  - Free gas in the peritoneal cavity: the final hazard of diathermy.
AB  - Fires and explosions in the operating theatre are rare events, but are
      devastating in terms of structural damage to the equipment in theatres and to
      human lives. Fuel, oxygen, and source of ignition are the three factors causing
      explosion. Explosion during emergency laparotomy for perforated bowel has not
      been reported in the literature. In the case reported here, fuel in the form of
      free gas came from the perforated stomach, after cardiopulmonary resuscitation.
      Oxygen used during cardiopulmonary resuscitation had entered the peritoneal
      cavity through the perforation. The source of ignition was diathermy. It was
      fatal.

PMID- 12185230
TI  - Eosinophilic gastroenteritis mimicking pancreatic cancer.
AB  - Eosinophilic gastroenteritis is a condition characterised by eosinophilic
      infiltration of the gastrointestinal tract. Biliary obstruction is an unusual
      presentation. A case where the initial investigations were consistent with
      carcinoma of the head of pancreas but the resection specimen showed no malignancy
      is presented. The diagnosis was suspected from a review of the patient's past
      history and confirmed by re-examination of the histology.

PMID- 12185231
TI  - A patient with bag of pancreatic stones.

PMID- 12185232
TI  - Homocysteine and "Buerger's disease".

PMID- 12185233
TI  - Type IV Ehlers-Danlos syndrome: a surgical emergency.

PMID- 12185234
TI  - Ischaemic foot: an unusual cause.

PMID- 12185235
TI  - Galactorrhoea in a 16 year old girl with a large sellar mass.

PMID- 12185236
TI  - An unusual complication of ulcerative colitis.

PMID- 12185243
TI  - Stimulation of the cell cycle and maize transformation by disruption of the plant
      retinoblastoma pathway.
AB  - The genome of the Mastreviruses encodes a replication-associated protein (RepA)
      that interacts with members of the plant retinoblastoma-related protein family,
      which are putative cell cycle regulators. Expression of ZmRb1, a maize
      retinoblastoma-related gene, and RepA inhibited and stimulated, respectively,
      cell division in tobacco cell cultures. The effect of RepA was mitigated by over
      expression of ZmRb1. RepA increased transformation frequency and callus growth
      rate of high type II maize germplasm. RepA-containing transgenic maize calli
      remained embryogenic, were readily regenerable, and produced fertile plants that
      transmitted transgene expression in a Mendelian fashion. In high type II,
      transformation frequency increased with the strength of the promoter driving RepA
      expression. When a construct in which RepA was expressed behind its native LIR
      promoter was used, primary transformation frequencies did not improve for two
      elite Pioneer maize inbreds. However, when LIR:RepA-containing transgenic embryos
      were used in subsequent rounds of transformation, frequencies were higher in the
      RepA+ embryos. These data demonstrate that RepA can stimulate cell division and
      callus growth in culture, and improve maize transformation.

PMID- 12185244
TI  - Formation of geometrically complex lipid nanotube-vesicle networks of higher
      order topologies.
AB  - We present a microelectrofusion method for construction of fluid-state lipid
      bilayer networks of high geometrical complexity up to fully connected networks
      with genus = 3 topology. Within networks, self-organizing branching nanotube
      architectures could be produced where intersections spontaneously arrange
      themselves into three-way junctions with an angle of 120 degrees between each
      nanotube. Formation of branching nanotube networks appears to follow a minimum
      bending energy algorithm that solves for pathway minimization. It is also
      demonstrated that materials can be injected into specific containers within a
      network by nanotube-mediated transport of satellite vesicles having defined
      contents. Using a combination of microelectrofusion, spontaneous nanotube pattern
      formation, and satellite-vesicle injection, complex networks of containers and
      nanotubes can be produced for a range of applications in, for example,
      nanofluidics and artificial cell design. In addition, this electrofusion method
      allows integration of biological cells into lipid nanotube-vesicle networks.

PMID- 12185245
TI  - Loss of microsatellite diversity and low effective population size in an
      overexploited population of New Zealand snapper (Pagrus auratus).
AB  - Although the effects of overfishing on species diversity and abundance are well
      documented, threats to the genetic diversity of marine fish populations have so
      far been largely neglected. Indeed, there seems to be little cause for concern,
      as even "collapsed" stocks usually consist of several million individuals,
      whereas population genetics theory suggests that only very small populations
      suffer significant loss of genetic diversity. On the other hand, in many marine
      species the genetically effective population size (N(e)), which determines the
      genetic properties of a population, may be orders of magnitude smaller than the
      census population size (N). Here, microsatellite analyses of a time series of
      archived scales demonstrated a significant decline in genetic diversity in a New
      Zealand snapper population during its exploitation history. Effective population
      sizes estimated both from the decline in heterozygosity and from temporal
      fluctuations in allele frequency were five orders of magnitude smaller than
      census population sizes from fishery data. If such low N(e)/N ratios are
      commonplace in marine species, many exploited marine fish stocks may be in danger
      of losing genetic variability, potentially resulting in reduced adaptability,
      population persistence, and productivity.

PMID- 12185246
TI  - Structural insights into peptide bond formation.
AB  - The large ribosomal subunit catalyzes peptide bond formation and will do so by
      using small aminoacyl- and peptidyl-RNA fragments of tRNA. We have refined at 3-A
      resolution the structures of both A and P site substrate and product analogues,
      as well as an intermediate analogue, bound to the Haloarcula marismortui 50S
      ribosomal subunit. A P site substrate, CCA-Phe-caproic acid-biotin, binds equally
      to both sites, but in the presence of sparsomycin binds only to the P site. The
      CCA portions of these analogues are bound identically by either the A or P loop
      of the 23S rRNA. Combining the separate P and A site substrate complexes into one
      model reveals interactions that may occur when both are present simultaneously.
      The alpha-NH(2) group of an aminoacylated fragment in the A site forms one
      hydrogen bond with the N3 of A2486 (2451) and may form a second hydrogen bond
      either with the 2' OH of the A-76 ribose in the P site or with the 2' OH of A2486
      (2451). These interactions position the alpha amino group adjacent to the
      carbonyl carbon of esterified P site substrate in an orientation suitable for a
      nucleophilic attack.

PMID- 12185247
TI  - Isolation of high-affinity GTP aptamers from partially structured RNA libraries.
AB  - Aptamers, RNA sequences that bind to target ligands, are typically isolated by in
      vitro selection from RNA libraries containing completely random sequences. To see
      whether higher-affinity aptamers can be isolated from partially structured RNA
      libraries, we selected for aptamers that bind GTP, starting from a mixture of
      fully random and partially structured libraries. Because stem-loops are common
      motifs in previously characterized aptamers, we designed the partially structured
      library to contain a centrally located stable stem-loop. We used an off-rate
      selection protocol designed to maximize the enrichment of high-affinity aptamers.
      The selection produced a surprisingly large number of distinct sequence motifs
      and secondary structures, including seven different aptamers with K(d)s ranging
      from 500 to 25 nanomolar. The engineered stem-loop was present in the three
      highest affinity aptamers, and in 12 of 13 independent isolates with a single
      consensus sequence, suggesting that its inclusion increased the abundance of high
      affinity aptamers in the starting pool.

PMID- 12185248
TI  - Evidence against stabilization of the transition state oxyanion by a pKa
      perturbed RNA base in the peptidyl transferase center.
AB  - The crystal structure of the ribosomal 50S subunit from Haloarcula marismortui in
      complex with the transition state analog CCdA-phosphate-puromycin (CCdApPmn) led
      to a mechanistic proposal wherein the universally conversed A2451 in the
      ribosomal active site acts as an "oxyanion hole" to promote the peptidyl
      transferase reaction [Nissen, P., Hansen, J., Ban, N., Moore, P.B., and Steitz,
      T.A. (2000) Science 289, 920-929]. In the model, close proximity (3 A) between
      the A2451 N3 and the nonbridging phosphoramidate oxygen of CCdApPmn suggested
      that the carbonyl oxyanion formed during the tetrahedral transition state is
      stabilized by hydrogen bonding to the protonated A2451 N3, the pKa of which must
      be perturbed substantially. We characterize the contribution of the putative
      hydrogen bond between the N3 of A2451 and the nonbridging phosphoramidate oxygen
      by using chemical protection and peptidyl transfer inhibition assays. If this
      putative hydrogen bond makes a significant thermodynamic contribution, then
      CCdApPmn-binding affinity to the 50S ribosomal subunit should be strongly pH
      dependent, with affinity increasing as the pH is lowered. We report that CCdApPmn
      binds 50S ribosomes with essentially equal affinity at all pH values between 5.0
      and 8.5. These data argue against a mechanism for peptidyl transfer in which a
      residue with near neutral pKa stabilizes the transition-state oxyanion, at least
      to the extent that CCdApPmn accurately mimics the transition state.

PMID- 12185249
TI  - The program of androgen-responsive genes in neoplastic prostate epithelium.
AB  - The human prostate gland is an important target organ of androgenic hormones.
      Testosterone and dihydrotestosterone interact with the androgen receptor to
      regulate vital aspects of prostate growth and function including cellular
      proliferation, differentiation, apoptosis, metabolism, and secretory activity.
      Our objective in this study was to characterize the temporal program of
      transcription that reflects the cellular response to androgens and to identify
      specific androgen-regulated genes (ARGs) or gene networks that participate in
      these responses. We used cDNA microarrays representing about 20,000 distinct
      human genes to profile androgen-responsive transcripts in the LNCaP
      adenocarcinoma cell line and identified 146 genes with transcript alterations
      more than 3-fold. Of these, 103 encode proteins with described functional roles,
      and 43 represent transcripts that have yet to be characterized. Temporal gene
      expression profiles grouped the ARGs into four distinct cohorts. Five
      uncharacterized ARGs demonstrated exclusive or high expression levels in the
      prostate relative to other tissues studied. A search of available DNA sequence
      upstream of 28 ARGs identified 25 with homology to the androgen response-element
      consensus-binding motif. These results identify previously uncharacterized and
      unsuspected genes whose expression levels are directly or indirectly regulated by
      androgens; further, they provide a comprehensive temporal view of the
      transcriptional program of human androgen-responsive cells.

PMID- 12185250
TI  - A far-red fluorescent protein with fast maturation and reduced oligomerization
      tendency from Entacmaea quadricolor (Anthozoa, Actinaria).
AB  - We performed the biochemical and biophysical characterization of a red
      fluorescent protein, eqFP611, from the sea anemone Entacmaea quadricolor cloned
      in Escherichia coli. With an excitation maximum at 559 nm and an emission maximum
      at 611 nm, the recombinant protein shows the most red-shifted emission and the
      largest Stokes shift of all nonmodified proteins in the green fluorescent protein
      family. The protein fluoresces with a high quantum yield of 0.45, although it
      resembles the nonfluorescent members of this protein class, as inferred from the
      absence of the key amino acid serine at position 143. Fluorescence is constant
      within the range pH 4-10. Red fluorophore maturation reaches a level of 90% after
      approximately 12 h by passing through a green intermediate. After complete
      maturation, only a small fraction of the green species (less than 1%) persists.
      The protein has a reduced tendency to oligomerize, as shown by its monomeric
      appearance in SDS/PAGE analysis and single-molecule experiments. However, it
      forms tetramers at higher concentrations in the absence of detergent.
      Fluorescence correlation spectroscopy reveals light-driven transitions between
      bright and dark states on submillisecond and millisecond time scales.
      Applicability of eqFP611 for in vivo labeling in eukaryotic systems was shown by
      expression in a mammalian cell culture.

PMID- 12185251
TI  - Short-term antigen presentation and single clonal burst limit the magnitude of
      the CD8(+) T cell responses to malaria liver stages.
AB  - Malaria sporozoites induce swift activation of antigen-specific CD8(+) T cells
      that inhibit the intracellular development of liver-stage parasites. The length
      of time of functional in vivo antigen presentation, estimated by monitoring the
      activation of antigen-specific CD8(+) T cells, is of short duration, with maximum
      T cell activation occurring within the first 8 h after immunization and lasting
      approximately 48 h. Although the magnitude of the CD8(+) T cell response closely
      correlates with the number of parasites used for immunization, increasing the
      time of antigen presentation by daily immunizations does not enhance the
      magnitude of this response. Thus, once a primary clonal burst is established, the
      CD8(+) T cell response becomes refractory or unresponsive to further antigenic
      stimulation. These findings strongly suggest that the most efficient strategy for
      the induction of primary CD8(+) T cell responses is the delivery of a maximal
      amount of antigen in a single dose, thereby ensuring a clonal burst that involves
      the largest number of precursors to become memory cells.

PMID- 12185252
TI  - Male germ-line stem cell potential is predicted by morphology of cells in
      neonatal rat testes.
AB  - Gonocytes are a transient population of male germ-line stem cells that are
      derived from primordial germ cells in the embryo and give rise to spermatogonial
      stem cells, which establish and maintain spermatogenesis in the postnatal testis.
      In contrast to spermatogonial stem cells, gonocytes can be identified easily in
      neonatal rat testis cell suspensions based on their large size and distinct
      morphology. Furthermore, histological analysis of testes from neonatal transgenic
      rats demonstrated that gonocytes are the only cells that express a lacZ reporter
      transgene. Two gonocyte subpopulations, designated pseudopod and round, were
      identified and isolated from neonatal (0-4 days postpartum) rat testis cell
      suspensions. Male germ-line stem cells, identified by their ability to produce
      and maintain colonies of spermatogenesis upon transplantation into infertile
      recipient testes, were present almost exclusively in the pseudopod gonocyte
      subpopulation. In contrast, annexin V staining indicated that the majority of
      round gonocytes undergo apoptosis. These results indicate that a nearly pure
      population of male germ-line stem cells can be prospectively identified in
      neonatal rat testis cell suspensions by morphological criteria. Together, the
      pseudopod and round gonocyte populations will provide powerful tools for the
      study of cellular mechanisms that control cell fates and the establishment of
      spermatogenesis in the postnatal testis.

PMID- 12185254
TI  - Neurosurgery and the neurologist.

PMID- 12185253
TI  - The tobacco salicylic acid-binding protein 3 (SABP3) is the chloroplast carbonic
      anhydrase, which exhibits antioxidant activity and plays a role in the
      hypersensitive defense response.
AB  - In plants, salicylic acid (SA) plays an important role in signaling both local
      and systemic defense responses. Previous efforts to identify SA effector proteins
      in tobacco have led to the isolation of two soluble cytoplasmic SA-binding
      proteins (SABPs): catalase, SABP, and an approximately 25-kDa protein, SABP2.
      Here we describe the identification of an SA-binding protein, SABP3, in the
      stroma of tobacco chloroplasts. SABP3 bound SA with an apparent dissociation
      constant (K(d)) of 3.7 microM and exhibited much greater affinity for
      biologically active than inactive analogs. Purification and partial sequencing of
      SABP3 indicated that it is the chloroplast carbonic anhydrase (CA). Confirming
      this finding, recombinant tobacco chloroplast CA exhibited both CA enzymatic and
      SA-binding activities. Expression of this protein in yeast also demonstrated that
      CA/SABP3 has antioxidant activity. A second gene encoding CA was also cloned, and
      its encoded protein was shown to behave similarly to that purified as SABP3.
      Finally, silencing of CA gene expression in leaves suppressed the Pto:avrPto
      mediated hypersensitive response in disease resistance. These results demonstrate
      that SA may act through multiple effector proteins in plants and shed further
      light on the function of CA in chloroplasts.

PMID- 12185255
TI  - Acute head injury for the neurologist.

PMID- 12185256
TI  - Head injury for neurologists.

PMID- 12185257
TI  - Hydrocephalus and shunts: what the neurologist should know.

PMID- 12185258
TI  - Raised intracranial pressure.

PMID- 12185260
TI  - Surgical disorders of the cervical spine: presentation and management of common
      disorders.

PMID- 12185259
TI  - Subarachnoid haemorrhage and intracranial aneurysms: what neurologists need to
      know.

PMID- 12185261
TI  - Surgical disorders of the thoracic and lumbar spine: a guide for neurologists.

PMID- 12185262
TI  - Occupancy and mechanism in antibody-mediated neutralization of animal viruses.
AB  - Neutralization of virus infectivity by antibodies is an important component of
      immunity to several virus infections. Here, the immunochemical basis for the
      action of neutralizing antibodies, and what role their induction of
      conformational changes in the antigen might play, is reviewed. Theories of the
      mechanisms by which antibodies neutralize virus infectivity in vitro are also
      presented. The theoretical and empirical foundation of the hypothesis that
      viruses are neutralized by a single antibody per virion is critically reviewed.
      The relationship between antibody occupancy on virions and the mechanism of
      neutralization is explored. Examples of neutralization mediated through antibody
      interference with virus attachment and entry are discussed and test implications
      of refined theories of neutralization by antibody coating of virions are
      formulated.

PMID- 12185263
TI  - Olfactory receptor neurons prevent dissemination of neurovirulent influenza A
      virus into the brain by undergoing virus-induced apoptosis.
AB  - Olfactory receptor neurons (ORNs) were infected upon intranasal inoculation with
      the R404BP strain of neurovirulent influenza A virus. Virus-infected neurons and
      a small fraction of neighbouring uninfected neurons displayed apoptotic
      neurodegeneration substantiated by the immunohistochemistry for activated caspase
      3 molecules and the terminal deoxynucleotidyl transferase-mediated dUTP nick end
      labelling method. However, virus infection was restricted within the peripheral
      neuroepithelium and all mice survived the infection. Virus-infected ORNs revealed
      upregulated expression of the Fas ligand molecules, activating the c-Jun N
      terminal kinase signal transduction pathway. In addition, Iba1-expressing
      activated microglia/macrophages appeared to partake in phagocytic activities,
      eventually clearing apoptotic bodies. These results raise the possibility that
      induction of apoptosis in olfactory receptor neurons at an early stage of
      infection may provide protective effects against invasion of the neurovirulent
      virus from the peripheral to the CNS.

PMID- 12185264
TI  - Complete nucleotide sequence of the M RNA segment of Andes virus and analysis of
      the variability of the termini of the virus S, M and L RNA segments.
AB  - Hantavirus pulmonary syndrome (HPS) has been recognized increasingly as a
      significant public health problem in South America since Andes virus was first
      discovered in Argentina. Here, the isolation of Andes virus is reported from an
      infected rodent captured in Argentina in close vicinity to the place of the first
      HPS case, AH1. The complete nucleotide sequences of the virus M segment, partial
      L segment and the termini of the S, M and L segment genome RNAs were determined.
      The Andes virus M RNA segment is 3671 nt in length and is predicted to encode a
      glycoprotein precursor 1138 aa in length; it generally resembles the other HPS
      associated hantaviruses in its organization. Relative to the G1 glycoprotein of
      other HPS-associated hantaviruses, an additional potential glycosylation site was
      found but this is located in the predicted cytoplasmic domain and is therefore
      unlikely to be glycosylated. In phylogenetic analyses, Andes virus, together with
      the more related hantaviruses, represented a monophyletic lineage. The S-terminal
      nucleotides were conserved relative to other New World hantaviruses. The M and L
      segment RNA termini had short deletions in the region believed to contain the
      sequence and structural features necessary for initiation of virus RNA
      replication and transcription. Clinical manifestations of Andes virus infections
      range from fulminant respiratory disease with high lethality to mild course
      without sequelae. Andes virus has also been associated with person-to-person
      transmission. Accumulation of Andes virus genetic data will be essential for
      understanding the factors that regulate virus replication and transmission and to
      determine the pathogenesis of HPS.

PMID- 12185265
TI  - High numbers of IL-2-producing CD8+ T cells during viral infection: correlation
      with stable memory development.
AB  - Using infections with lymphocytic choriomeningitis virus (LCMV) and vesicular
      stomatitis virus in mice as model systems, we have investigated the ability of
      antigen-primed CD8+ T cells generated in the context of viral infections to
      produce IL-2. Our results indicate that acute immunizing infection normally leads
      to generation of high numbers of IL-2-producing antigen-specific CD8+ T cells. By
      costaining for IL-2 and IFN-gamma intracellularly, we found that IL-2-producing
      cells predominantly constitute a subset of cells also producing IFN-gamma.
      Comparison of the kinetics of generation revealed that IL-2-producing cells
      appear slightly delayed compared with the majority of IFN-gamma producing cells,
      and the relative frequency of the IL-2-producing subset increases with transition
      into the memory phase. In contrast to acute immunizing infection, few IL-2
      producing cells are generated during chronic LCMV infection. Furthermore, in MHC
      class II-deficient mice, which only transiently control LCMV infection, IL-2
      producing CD8+ T cells are initially generated, but by 4 weeks after infection
      this subset has nearly disappeared. Eventually the capacity to produce IFN-gamma
      also becomes impaired, while cell numbers are maintained at a level similar to
      those in wild-type mice controlling the infection. Taken together, these findings
      indicate that phenotyping of T cell populations based on capacity to produce
      cytokines, and especially IL-2, can provide important information as to the
      functional status of the analysed cell subset. Specifically, combined analysis of
      the capacity to produce IL-2 and IFN-gamma can be used as a predictor for loss of
      function within the CD8+ T cell compartment.

PMID- 12185266
TI  - Apoptosis induction by the Therien and vaccine RA27/3 strains of rubella virus
      causes depletion of oligodendrocytes from rat neural cell cultures.
AB  - The induction of cell death by the Therien strain of rubella virus (RVT), and the
      vaccine RA27/3 strain, was investigated in mixed glial cell cultures derived from
      the rat CNS. Cell death induction in Vero and rat glial cells by RVT and RA27/3
      was dependent on virus replication. In both cell types and for both virus
      strains, cell death induction had the hallmarks of apoptosis, as detected by DNA
      laddering, terminal deoxynucleotidyl transferase-mediated dUTP nick end labelling
      staining and Annexin V staining. For rat mixed glial cells, the depletion of
      oligodendrocytes was due to the induction of apoptosis for both virus strains.
      The induction of apoptosis in H358a cells, which carry a homozygous deletion of
      the p53 gene, indicated that a p53-independent pathway can be involved. The
      induction of cell death by RVT and RA27/3 in Vero and rat glial cells was
      associated with caspase-3 activity. It is concluded that rubella virus (RV)
      induces apoptosis in oligodendrocytes in rat glial cell cultures by a caspase
      dependent pathway and that similar mechanisms occur for both the RVT laboratory
      strain and the vaccine RA27/3 strain. The tropism of both strains of RV for
      oligodendrocytes and the induction of apoptosis in such cells may have important
      implications for the mechanism of virus neuropathogenesis.

PMID- 12185268
TI  - Identification of the glycosaminoglycan-binding site on the glycoprotein E(rns)
      of bovine viral diarrhoea virus by site-directed mutagenesis.
AB  - Bovine viral diarrhoea virus (BVDV) envelope glycoprotein E(rns) interacts with
      highly sulphated heparin-like glycosaminoglycans (GAGs) located on the cell
      surface as an early step in virus infection of cells. Site-directed mutagenesis
      of recombinant E(rns) was undertaken and analysis of mutants by heparin-affinity
      chromatography and cell surface binding showed that a cluster of basic amino
      acids (480KKLENKSK487) near the C terminus of E(rns) was essential for binding.
      Mutants with amino acid substitutions of lysine residues 481 and 485 in E(rns)
      reduced the binding of E(rns) to immobilized heparin and cellular GAGs but
      retained ribonuclease activity. In contrast to normal E(rns), E(rns) that was
      unable to bind to cells also failed to inhibit BVDV infection of cells when the
      cells were pre-incubated with E(rns). It is proposed that the cluster of basic
      residues (480KKLENKSK487) localized at the C-terminal end of E(rns) constitutes a
      GAG-binding site.

PMID- 12185267
TI  - Hepatitis C virus core protein represses the p21 promoter through inhibition of a
      TGF-beta pathway.
AB  - The increased proliferation rate of hepatocytes is one of the major risk factors
      for the development of hepatocellular carcinoma. In this study, we investigated
      the mechanism by which hepatitis C virus (HCV) core protein represses
      transcription of the universal cyclin-dependent kinase inhibitor p21 gene in
      murine fibroblast NIH 3T3 cells. From the transient reporter assays of p21
      promoter, we found that the TGF-beta-responsive element (TbetaRE) located between
      -83 and -74 of the p21 promoter is responsible for the effect. The TGF-beta
      induced p21 promoter activity was specifically decreased by HCV core protein and
      in the presence of the inhibitory Smad7 the repression effect was almost
      completely abolished. Furthermore, HCV core protein stimulated the growth rate of
      NIH 3T3 cells and could overcome growth arrest by TGF-beta but not by butyrate,
      suggesting that HCV core protein stimulates cell cycle progression by repressing
      p21 transcription through a TGF-beta pathway.

PMID- 12185269
TI  - Quasispecies in the 5' untranslated genomic region of bovine viral diarrhoea
      virus from a single individual.
AB  - The variability of the 5' untranslated genomic region (5'UTR) of bovine viral
      diarrhoea virus (BVDV) RNA obtained from a single individual was analysed. Lung,
      kidney and spleen tissues from a naturally infected foetus were used as the
      source of viral RNA. A fragment of 288 bases of the internal ribosome entry site
      from the BVDV 5'UTR was amplified by RT-PCR using a proofreading DNA polymerase.
      PCR products were cloned into pGem and, subsequently, transformed into
      Escherichia coli. The single-strand conformational polymorphisms of 158 lung
      derived clones were analysed; a total of 11 banding patterns was observed. DNAs
      corresponding to all patterns were sequenced. Of the randomly selected clones, 11
      and 10 clones derived from the kidney and spleen, respectively, were also
      sequenced. All sequences presented differences ranging from 1 to 6 nt
      substitutions. Analysis of the secondary structure of the variant sequences and
      comparisons to variant nucleotide sites from the 5'UTR of several BVDV isolates
      showed that the observed changes were almost free of randomness. Clustering and
      phylogenetic analyses suggested the existence of low-kinetic variants. BVDV
      quasispecies may be involved in establishing persistent infections by means of
      eluding maternal antibodies. The methods described here may be adapted easily
      both to analyse large numbers of samples from other genomic regions and for the
      study of BVDV quasispecies evolution in other systems.

PMID- 12185270
TI  - Circulating and cell-bound antibodies increase coxsackievirus B4-induced
      production of IFN-alpha by peripheral blood mononuclear cells from patients with
      type 1 diabetes.
AB  - Increased levels of IFN-alpha have been found in patients with type 1 diabetes
      who have detectable levels of coxsackievirus B4 (CVB4) RNA in their blood. The
      IFN-alpha-inducing activity of CVB4 in vitro is weak but can be enhanced by human
      IgGs. Therefore, it was investigated in vitro whether a preferential IFN-alpha
      response of peripheral blood mononuclear cells (PBMCs) to CVB4 exists in patients
      with type 1 diabetes (n=56) compared with healthy subjects (n=20) and whether
      antibodies play a role. In patients, the levels of IFN-alpha obtained after
      stimulation by PBMCs with CVB4 were higher (P=0.008), an individual IFN-alpha
      response by PBMCs to CVB4 was more frequent (P=0.0004) and increased levels of
      IFN-alpha were observed in CVB4-infected whole blood cultures. The IFN-alpha
      inducing activity of patients plasma and IgGs mixed with CVB4 and then added to
      PBMCs was high in comparison with healthy subjects (P<0.001) and was inhibited by
      preincubating the cells with anti-FcgammaRII, anti-FcgammaRIII and anti-CAR
      (coxsackievirus and adenovirus receptor) antibodies. The strong IFN-alpha
      responsiveness of PBMCs to CVB4 suggested that IgGs bound to the cell surface
      might play a role. A short 56 degrees C incubation of PBMCs from patients
      responsive to CVB4 generated supernatants, which, when added to cells, exhibited
      IFN-alpha-enhancing activity in combination with CVB4, whereas those of controls
      did not. Specific antibodies for FcgammaRI, FcgammaRII and CAR inhibited this
      activity. These studies demonstrate that CVB4, through interactions with
      circulating and/or cell-bound IgGs, can strongly induce the production of IFN
      alpha by PBMCs from patients with type 1 diabetes.

PMID- 12185271
TI  - Poliovirus transcytosis through M-like cells.
AB  - During the digestive-tract phase of infection, poliovirus (PV) is found in the
      oropharynx and the intestine. It has been proposed that PV enters the organism by
      crossing M cells, which are scattered in the epithelial sheet covering lymphoid
      follicles of Peyer's patches. However, PV translocation through M cells has never
      been demonstrated. A model of M-like cells has been previously developed using
      monolayers of polarized Caco-2 enterocytes cocultured with lymphocytes isolated
      from Peyer's patches. In this model, lymphoepithelial interactions trigger the
      appearance of epithelial cells having morphological and functional
      characteristics of M cells. We have demonstrated efficient, temperature-dependent
      PV transcytosis in Caco-2 cell monolayers containing M-like cells. This
      experimental evidence is consistent with M cells serving as gateways allowing PV
      access to the basal face of enterocytes, the underlying immune follicle cells,
      and PV transport toward mesenteric lymph nodes.

PMID- 12185272
TI  - Replication of a hepatitis A virus replicon detected by genetic recombination in
      vivo.
AB  - Unlike other picornaviruses, hepatitis A virus (HAV) replicates so inefficiently
      in cell culture that the study of its RNA biosynthesis presents a major
      experimental challenge. To assess viral RNA replication independent of particle
      formation, a subgenomic replicon representing a self-replicating RNA was
      constructed by replacing the P1 domain encoding the capsid proteins with the
      firefly luciferase sequence. Although translation of the HAV replicon was as
      efficient as a similar poliovirus replicon, the luciferase activity derived from
      replication of the HAV construct was more than 100-fold lower than that of
      poliovirus. The replication capacity of the HAV replicon was clearly demonstrated
      by its ability to recombine genetically with a non-viable, full-length HAV genome
      that served as capsid donor and thus to rescue a fully infectious virus. In
      contrast to a replication-deficient replicon, co-expression of the genetically
      marked and replication-competent HAV replicon with several lethally mutated HAV
      genomes resulted in the successful rescue of infectious HAV with a unique genetic
      marker. Our data suggest: (i) that autonomous HAV RNA replication does not
      require sequences for the HAV structural proteins; and (ii) that low-level genome
      replication can unequivocally be demonstrated by the rescue of infectious virus
      after co-expression with non-viable genomes.

PMID- 12185273
TI  - Natural genetic recombination between co-circulating heterotypic enteroviruses.
AB  - Natural recombination in poliovirus is a frequent phenomenon. In practice,
      whenever different genotypes have the opportunity to infect the same individual,
      a high proportion of viruses with recombinant genomes are excreted. To determine
      whether enteroviruses other than poliovirus can naturally produce viable virions
      with recombinant genomes, we studied the molecular features of two distant
      regions of the viral genomes - the VP1 coding region and the 3D polymerase coding
      region - of the echovirus serotypes associated with a large outbreak of aseptic
      meningitis. Nucleotide sequences of nine epidemic strains [belonging to echovirus
      serotypes 4 (E4), 7 (E7) and 30 (E30)] in the two genomic regions (300 nt of VP1
      and 520 nt of 3D polymerase) were compared to prototype and field strains, and
      phylogenetic trees were generated from alignments. In the VP1 region, each of the
      three epidemic serotypes clustered with the homotypic prototype strain, whereas
      in the 3D polymerase region, E7 and E30 grouped as a single cluster, distant from
      the two corresponding prototype strains. This suggests that one of these two E7
      and E30 strains has evolved through recombination with the other or that both
      have acquired the 3D polymerase coding region from a common ancestor. Our results
      suggest that such genetic recombinations between different echovirus serotypes
      are possible when multiple epidemic strains are circulating simultaneously.

PMID- 12185274
TI  - The putative capsid protein of the newly identified avian hepatitis E virus
      shares antigenic epitopes with that of swine and human hepatitis E viruses and
      chicken big liver and spleen disease virus.
AB  - We recently identified a novel virus, designated avian hepatitis E virus (avian
      HEV), from chickens with hepatitis-splenomegaly (HS) syndrome in the USA. We
      showed that avian HEV is genetically related to swine and human HEVs. Here we
      report the antigenic cross-reactivity of the putative open reading frame 2 (ORF2)
      capsid protein of avian HEV with those of swine and human HEVs and the Australian
      chicken big liver and spleen disease virus (BLSV). The region encoding the C
      terminal 268 amino acid residues of avian HEV ORF2 was cloned into expression
      vector pRSET-C. The truncated ORF2 protein was expressed in E. coli as a fusion
      protein and purified by affinity chromatography. Western blot analysis revealed
      that the avian HEV ORF2 protein reacted with antisera against the Sar-55 strain
      of human HEV and with convalescent antisera against swine HEV and the US2 strain
      of human HEV, as well as with antiserum against BLSV. Convalescent sera from
      specific-pathogen-free chickens experimentally infected with avian HEV also
      reacted with the recombinant capsid proteins of swine HEV and Sar-55 human HEV.
      Antisera against the US2 human HEV also reacted with recombinant ORF2 proteins of
      both swine HEV and Sar-55 human HEV. The antigenic cross-reactivity of the avian
      HEV putative capsid protein with those of swine and human HEVs was further
      confirmed, for the most part, by ELISA assays. The data indicate that avian HEV
      shares certain antigenic epitopes in its putative capsid protein with swine and
      human HEVs, as well as with BLSV. The results have implications for HEV diagnosis
      and taxonomy.

PMID- 12185276
TI  - Cloning of complete genome sets of six dsRNA viruses using an improved cloning
      method for large dsRNA genes.
AB  - Cloning full-length large (>3 kb) dsRNA genome segments from small amounts of
      dsRNA has thus far remained problematic. Here, a single-primer amplification
      sequence-independent dsRNA cloning procedure was perfected for large genes and
      tailored for routine use to clone complete genome sets or individual genes. Nine
      complete viral genome sets were amplified by PCR, namely those of two human
      rotaviruses, two African horsesickness viruses (AHSV), two equine encephalosis
      viruses (EEV), one bluetongue virus (BTV), one reovirus and bacteriophage Phi12.
      Of these amplified genomes, six complete genome sets were cloned for viruses with
      genes ranging in size from 0.8 to 6.8 kb. Rotavirus dsRNA was extracted directly
      from stool samples. Co-expressed EEV VP3 and VP7 assembled into core-like
      particles that have typical orbivirus capsomeres. This work presents the first
      EEV sequence data and establishes that EEV genes have the same conserved termini
      (5' GUU and UAC 3') and coding assignment as AHSV and BTV. To clone complete
      genome sets, one-tube reactions were developed for oligo-ligation, cDNA synthesis
      and PCR amplification. The method is simple and efficient compared to other
      methods. Complete genomes can be cloned from as little as 1 ng dsRNA and a
      considerably reduced number of PCR cycles (22-30 cycles compared to 30-35 of
      other methods). This progress with cloning large dsRNA genes is important for
      recombinant vaccine development and determination of the role of terminal
      sequences for replication and gene expression.

PMID- 12185275
TI  - Intramolecular disulfide bonding is essential for betanodavirus coat protein
      conformation.
AB  - Here we report on the conformational changes that are responsible for the
      appearance of the Dicentrarchus labrax encephalitis virus (DlEV) coat protein as
      a doublet in SDS-PAGE. Wild-type and mutated forms of the coat protein cDNA were
      expressed in E. coli. The study of the resulting recombinant molecules excluded
      the possibility of the involvement of a precursor autocatalysis mechanism or a
      ribosomal frameshifting event in the doublet formation. The appearance of the
      coat protein doublet was found to be beta-mercaptoethanol sensitive. Based on
      this observation, we carried out substitution of all cysteine residues. The
      obtained results demonstrated the importance of intramolecular disulfide bonding
      between cysteines 187 and 201 on coat protein conformational changes.

PMID- 12185277
TI  - Human immunodeficiency virus type 1 Vif binds the viral protease by interaction
      with its N-terminal region.
AB  - The vif gene, one of the six auxiliary genes of human immunodeficiency virus
      (HIV), is essential for virus propagation in peripheral blood lymphocytes and
      macrophages and in certain T-cell lines. Previously, it was demonstrated that Vif
      inhibits the autoprocessing of truncated HIV type 1 (HIV-1) Gag-Pol polyproteins
      expressed in bacterial cells, as well as the protease-mediated cleavage of
      synthetic peptides in vitro. Peptides derived from the aa 78-98 region in the Vif
      molecule specifically inhibit and bind the HIV-1 protease in vitro and arrest the
      production of infectious viruses in HIV-1-infected cells. This study demonstrates
      that (i) purified recombinant Vif protein and HIV-1 but not avian sarcoma
      leukaemia virus protease specifically bind each other and (ii) the interaction
      between these two proteins takes place at the N terminus of the protease (aa 1-9)
      and the central part of Vif (aa 78-98). The data presented in this report suggest
      a model in which Vif interacts with the dimerization sites of the viral protease.

PMID- 12185278
TI  - PCR-based cloning and immunocytological titration of infectious porcine
      endogenous retrovirus subgroup A and B.
AB  - Two pig endogenous retroviruses (PERV), PERV-A and -B, productively infect human
      cells and are therefore considered to constitute a potential risk in pig-to-human
      xenotransplantation. A PCR-based cloning technique to isolate infectious PERV
      proviruses was established. Overlapping 3' half and 5' halves of PERV proviral
      genomes were amplified using DNA extracted from human 293 cells infected with
      PERV-A or -B. These clones were fused at a unique restriction site in the
      overlapping region and tested for their infectivity. Representative constructs
      possessed the same infectious properties as their parent isolates. We also
      developed a polyclonal anti-PERV serum by using recombinant PERV capsid protein
      derived from one of the infectious constructs as immunogen and established an
      immunocytological method for detection and titration of PERV infection. This
      detection method proved to be more sensitive than the current method of choice
      (transfer of MLV-lacZ vectors) for infectivity assessment of PERV. These findings
      should be considered for future characterization of PERV isolates.

PMID- 12185279
TI  - Identification of R-peptides in envelope proteins of C-type retroviruses.
AB  - Activation of the murine leukaemia virus (MLV) envelope protein (Env) requires
      proteolytic cleavage of the R-peptide, a 16 amino acid C-terminal part of the
      cytoplasmic tail (C-tail) of Env. This paper demonstrates the presence of R
      peptides in Env proteins of C-type retroviruses of simian, avian and porcine
      origin. Sequence alignment with the MLV C-tail led to the identification of a
      conserved hydrophobic protease cleavage motif located in the centre of retroviral
      Env protein C-tails. Expression of Env proteins, truncated at the predicted
      cleavage sites, of spleen necrosis virus (SNV), gibbon ape leukaemia virus and
      porcine endogenous retroviruses resulted in cell-cell fusion as monitored by
      microscopy and reporter gene fusion assays. Western blot analysis of MLV
      particles pseudotyped with the SNV Env protein demonstrated proteolytic cleavage
      of the SNV R-peptide by the MLV protease. Our data suggest that activation of
      membrane fusion by R-peptide cleavage is a common mode in C-type retroviruses.

PMID- 12185280
TI  - Glycoprotein B plays a predominant role in mediating herpes simplex virus type 2
      attachment and is required for entry and cell-to-cell spread.
AB  - Heparan sulfate moieties serve as receptors for initial binding of herpes simplex
      virus types 1 and 2 (HSV-1 and -2) to cells. Deletion of HSV-1 glycoprotein C (gC
      1) but not HSV-2 gC (gC-2) results in virions with reduced specific binding
      activity (virus particles bound per cell) and specific infectivity (p.f.u. per
      particle), suggesting that for HSV-1, but not HSV-2, gC plays a major role in
      mediating virus attachment. To test the hypothesis that glycoprotein B (gB), the
      other heparin-binding glycoprotein, mediates HSV-2 attachment, HSV-2 viruses
      deleted in gB-2 alone or deleted in both gB-2 and gC-2 were constructed. These
      viruses were grown on complementing or non-complementing cells and were compared
      with parental HSV-2(G) or a gC-2-deleted HSV-2 mutant (with respect to ability to
      bind and infect cells). At equivalent input concentrations of purified virions,
      significantly fewer gB-2-deleted virions bound to cells compared to parental HSV
      2(G) or virus grown on complementing cells. In addition, viruses deleted in gB-2
      were non-infectious. No immediate early proteins were detected in cells infected
      with gB-2-deleted virus harvested from non-complementing Vero cells, whereas
      these proteins were readily detected 4 h post-infection in cells infected with
      virus grown on complementing cells or with parental viruses. Viruses deleted in
      gB-2 failed to spread cell to cell, as evidenced by the inability to form
      plaques. Together these studies demonstrate that gB-2 plays a key role in
      mediating HSV-2 attachment and is required for entry and cell-to-cell spread.
      This glycoprotein is an important target for development of novel antiviral
      drugs.

PMID- 12185281
TI  - Susceptibility of sensory neurons to apoptosis following infection by bovine
      herpesvirus type 1.
AB  - Like other members of the alpha subfamily of herpesviruses, bovine herpesvirus
      type 1 (BHV-1) establishes latent infections in sensory neurons. BHV-1 induces
      apoptosis in lymphoid cells in vivo and in epithelial cell lines, but the ability
      of BHV-1 to induce apoptosis in sensory neurons remains unknown. In this report,
      the susceptibility of rabbit ganglionic neurons to infection by BHV-1 was
      examined in vitro and in vivo. Following infection of cultured neurons with BHV
      1, hallmarks of apoptosis such as chromatin condensation, DNA fragmentation and
      membrane blebbing were detected. The appearance of these changes was preceded by
      active viral DNA replication as determined by in situ hybridization. When viral
      DNA replication was blocked by treatment of cultures with an inhibitor of
      eukaryotic DNA polymerases, apoptosis but not virus attachment to neurons or
      bICP0 gene expression was completely prevented. Taken together, these results
      demonstrate that sensory neurons are not intrinsically resistant to BHV-1-induced
      apoptosis and that viral DNA replication plays a role in triggering the apoptotic
      programme. Infection of rabbits with BHV-1 resulted in pathological changes in
      the trigeminal ganglia (TG) which included mononuclear cell infiltration and
      neuronophagia. Morphological evidence of apoptosis was not detected in neurons,
      even in cells with advanced cytophatology. Furthermore, whereas DNA fragmentation
      was common in infiltrating cells, it was very rare and sporadic in neurons.
      Therefore, mechanisms in the TG should exist to prevent neuronal apoptosis upon
      BHV-1 infection.

PMID- 12185282
TI  - The terminal repeats and latency-associated nuclear antigen of herpesvirus
      saimiri are essential for episomal persistence of the viral genome.
AB  - The simian herpesvirus saimiri (HVS) induces malignant T cell lymphomas and is
      closely related to Kaposi's sarcoma-associated herpesvirus (KSHV or HHV-8). Both
      belong to the gamma-2 herpesvirus subgroup. The viral genome of HVS consists of a
      unique region (L-DNA) that contains all of the viral genes flanked by non-coding
      terminal repeats (H-DNA). Here we describe the cloning of a 113 kb restriction
      fragment containing the L-DNA of an oncogenic HVS strain in an F' replicon-based
      E. coli vector. Cloned DNA was infectious and the ends of the progeny viral
      genome consisted of amplified tandem alternating repeats of vector and a single H
      DNA unit. T cells infected with these viruses contained the linear DNA typically
      found a few weeks after infection, but were unable to form episomal circular
      viral DNA, which is the latent form of the viral genome. Recombinant viruses with
      reconstructed H-DNA were generated and T cells infected with these rescued
      viruses contained high copy numbers of episomal DNA. Plasmids expressing the
      latency-associated nuclear antigen (LANA) and containing various numbers of H-DNA
      repeats stably replicated as episomes, but constructs containing three repeat
      units produced the highest copy numbers. These data show that intact and multiple
      terminal repeats are essential components for episomal replication in latently
      infected T cells. Moreover, LANA and terminal repeats are sufficient for stable
      plasmid persistence. Cloned HVS can also be utilized for mutagenesis of HVS and
      for the expression of foreign genes through efficient manipulation of plasmids in
      E. coli.

PMID- 12185283
TI  - LPS-binding protein and CD14-dependent attachment of hepatitis B surface antigen
      to monocytes is determined by the phospholipid moiety of the particles.
AB  - It was observed recently that recombinant yeast-derived hepatitis B surface
      antigen (rHBsAg) particles, which contain the S protein only, bind almost
      exclusively to monocytes. It is shown here that binding requires the presence of
      the LPS receptor CD14. Furthermore, evidence is presented that a domain on CD14
      that is identical to or largely overlaps with the LPS-binding pocket is
      instrumental for the attachment of rHBsAg. Additionally, it is shown that the
      heat-labile LPS-binding protein (LBP) catalyses the binding of rHBsAg to the
      cells. Remarkably, natural plasma-derived HBsAg (pHBsAg) does not have this
      property. pHBsAg devoid of its lipids and reconstituted with phosphatidylserine
      or phosphatidylglycerol acquires the characteristic of yeast-derived HBsAg.
      Clearly, the interaction of rHBsAg with the cell membrane is determined by the
      presence of charged phospholipids that are absent in pHBsAg. Although a lipid
      receptor interaction is suggested, antibody-inhibition experiments suggest a
      possible involvement of the C-terminal region of the S protein in the interaction
      with monocytes. The possible implications of these observations for hepatitis B
      virus (HBV) infection and HBV vaccine efficiency are discussed.

PMID- 12185285
TI  - Absence of canine oral papillomavirus DNA following prophylactic L1 particle
      mediated immunotherapeutic delivery vaccination.
AB  - In the canine oral papillomavirus (COPV) model, following wart regression, COPV
      DNA was detected by PCR at the challenge site. However, following particle
      mediated immunotherapeutic delivery (PMID) of COPV L1 and subsequent challenge,
      no COPV DNA could be detected. These data support PMID of COPV L1 as a protective
      vaccine and suggest that PMID of L1 may induce virus clearance.

PMID- 12185284
TI  - Detection and significance of a G1862T variant of hepatitis B virus in Chinese
      patients with fulminant hepatitis.
AB  - The prevalence of a G1862T variant of hepatitis B virus (HBV) has been
      investigated in patients with fulminant hepatitis and chronic liver disease,
      using primer mismatch amplification, followed by restriction fragment length
      polymorphism analysis. This variant was five times more common in patients with
      fulminant hepatitis (13.7%, 7 of 52) than in chronic carriers (2.5%, 2 of 81).
      The G-->T substitution at position 1862 leads to an amino acid change in codon 17
      of the precore protein of the virus, which is part of a signal peptidase
      recognition motif. Variants with this mutation were only seen in patients
      infected with genotype B. In vitro translation experiments showed that this
      variant has greatly reduced capacity to produce hepatitis B e antigen (HBeAg)
      from its precore protein precursor. Furthermore, 88.5% of patients with fulminant
      hepatitis had mutations that are known to be associated with abrogated or reduced
      production of HBeAg. This suggests that, following HBV infection, the absence or
      reduced amounts of HBeAg may be a contributing factor in fulminant disease.

PMID- 12185286
TI  - Felis domesticus papillomavirus, isolated from a skin lesion, is related to
      canine oral papillomavirus and contains a 1.3 kb non-coding region between the E2
      and L2 open reading frames.
AB  - We have characterized the complete genome (8300 bp) of an isolate of Felis
      domesticus papillomavirus (FdPV) from a domestic cat with cutaneous
      papillomatosis. A BLAST homology search using the nucleotide sequence of the L1
      open reading frame demonstrated that the FdPV genome was most closely related to
      canine oral papillomavirus (COPV). A 384 bp non-coding region (NCR) was found
      between the end of L1 and the beginning of E6, and a 1.3 kbp NCR was located
      between the end of E2 and the beginning of L2. Phylogenetic analysis placed FdPV
      in the E3 clade with COPV. Both viruses contain the atypical second NCR, which
      has no homology with sequences in existing databases.

PMID- 12185287
TI  - Analysis of mouse polyomavirus mutants with lesions in the minor capsid proteins.
AB  - Polyomavirus mutants E, Q and H, expressing non-myristylated VP2, were generated
      by replacing the N-terminal glycine residue with glutamic acid, glutamine or
      histidine, respectively. Viruses mutated in either VP2 or VP3 translation
      initiation codons were also prepared. All mutated genomes, when transfected into
      murine host cells, gave rise to viral particles. Infectivity of VP2- and VP3-
      viruses, as measured by the number of cells expressing viral antigens, was
      dramatically diminished, indicative of defects in the early stages of infection.
      In contrast, the absence of a myristyl moiety on VP2 did not substantially affect
      the early steps of virus infection. No differences in numbers of cells expressing
      early or late viral antigens were observed between wild-type (wt) and E or Q myr-
      viruses during the course of a life cycle. Furthermore, no delay in virus DNA
      replication was detected. However, when cells were left for longer in culture,
      the number of infected cells, measured by typical virus bursts, was much lower
      when mutant rather than wt genomes were used. In situ, cell fractionation studies
      revealed differences in the interaction of viral particles with host cell
      structures. The infectivity of mutants was affected not only by loss of the
      myristyl group on VP2, but also, and to a greater extent, by alterations of the N
      terminal amino acid composition.

PMID- 12185288
TI  - No association between human parvovirus B19 and testicular germ cell cancer.
AB  - The incidence of testicular germ cell cancer, which is the most common cancer
      among young male adults, is increasing. The aetiology remains unknown, although a
      virus has been proposed. A previous study has shown a high prevalence of human
      parvovirus B19 (B19) DNA in the testes of patients with testicular germ cell
      tumours (85%) and suggested that B19 may play a role in tumour development. To
      address this question of causality, seroreactivity to B19 was studied among cases
      (n=80) and controls (n=241) using serum samples drawn before the onset of
      disease, in addition to an elucidation of the frequency of virus DNA in a
      retrospectively collected 2-year testicular carcinoma series. No association was
      found between B19 seropositivity and the risk of testicular cancer (odds
      ratio=1.03; 95% confidence interval=0.60-1.77) nor was there any dose-response
      relation (P for trend=0.53). This study did, however, confirm the observation
      that B19 DNA can be detected in testicular carcinoma tissue, as 4 of 24 cases
      were found to be positive, while no B19 DNA could be detected in the control
      cases. It is speculated that this finding may be due to susceptibility of the
      carcinoma cells to B19 virus owing to high-level expression of the viral receptor
      glycosphingolipid (Gb4) and possible other putative cellular factors resulting in
      a localized persistence initiated after the development of cancer.

PMID- 12185289
TI  - Silencing of a viral RNA silencing suppressor in transgenic plants.
AB  - High expression levels of the helper component proteinase (HC(pro)), a known
      virus suppressor of RNA silencing, were attained in Nicotiana benthamiana
      transformed with the HC(pro) cistron of Potato virus A (PVA, genus Potyvirus). No
      spontaneous silencing of the HC(pro) transgene was observed, in contrast to the
      PVA coat protein (CP)-encoding transgene in other transgenic lines. HC(pro)
      transgenic plants were initially susceptible to PVA and were systemically
      infected by 14 days post-inoculation (p.i.) but, 1 to 2 weeks later, the new
      expanding leaves at positions +6 and +7 above the inoculated leaf showed a
      peculiar recovery phenotype. Leaf tips (the oldest part of the leaf) were
      chlorotic and contained high titres of PVA, whereas the rest of the leaf was
      symptomless and contained greatly reduced or non-detectable levels of viral RNA,
      CP and transgene mRNA. The spatial recovery phenotype suggests that RNA silencing
      is initiated in close proximity to meristematic tissues. Leaves at position +8
      and higher were symptomless and virus-free but not completely resistant to
      mechanical inoculation with PVA. However, they were not infected with the virus
      systemically transported from the lower infected leaves, suggesting a vascular
      tissue-based resistance mechanism. Recovery of the HC(pro)-transgenic plants from
      infection with different PVA isolates was dependent on the level of sequence
      homology with the transgene. Methylation of the HC(pro) transgene followed
      recovery. These data show that the transgene mRNA for a silencing suppressor can
      be silenced by a presumably 'strong' silencing inducer (replicating homologous
      virus).

PMID- 12185290
TI  - "Target and control" en route to "cure and elimination:" we must prepare for good
      health and longevity.

PMID- 12185291
TI  - Staging of regional nodes in AJCC stage I and II melanoma: 18FDG PET imaging
      versus sentinel node detection.
AB  - PRIMARY PURPOSE: The staging of regional nodes by means of sentinel node
      detection has been shown to accurately detect subclinical nodal metastases from
      cutaneous melanoma. On the other hand, the oncological applications of 18F-fluoro
      2-deoxy-D-glucose positron emission tomography (18FDG PET) are, nowadays, firmly
      established. However, the sensitivity of such metabolic imaging for staging the
      regional nodes in primary melanoma remains debatable. We prospectively assessed
      the actual value of PET for detecting sentinel node metastases in 21 consecutive
      patients presenting with early-stage melanoma. MATERIALS AND METHODS: Twenty-one
      melanoma patients scheduled for lymphatic mapping and sentinel lymphadenectomy
      underwent fully corrected whole-body PET using 18FDG. In all cases, the disease
      was initially classified as either stage I or II, from the latest version of the
      American Joint Committee on Cancer staging system. The sentinel node detection
      was systematically performed within the week following the PET scan. Serial
      sections of the sentinel nodes were analyzed by both conventional pathology and
      immunohistochemical staining. Metastatic sentinel nodes were also assessed for
      the size of tumor deposits and the degree of nodal involvement (focal, partial,
      or massive). The median follow-up time was 12 months. RESULTS: Six of the 21
      patients (28.5%) had an involved sentinel node. PET was positive in only one case
      with a sentinel node >1 cm. In the five other cases, the sentinel nodes missed by
      PET were <1 cm with focal and/or partial involvements. One patient, free of
      regional nodal metastases in both sentinel node detection and PET imaging, had,
      however, a same-basin recurrence 3 months later. In another case, PET had one
      false positive result. Overall, the sentinel detection of subclinical nodal
      metastases had a sensitivity of 86%. PET detected only 14% of sentinel node
      metastases. CONCLUSIONS: Sentinel node detection remains the procedure of choice
      for detecting subclinical lymph node involvement from primary cutaneous melanoma.
      Owing to its limited spatial resolution, PET appears insufficiently sensitive to
      identify microscopic nodal metastases. As a practical consequence, metabolic
      imaging is not recommended as a first-line imaging strategy for staging regional
      lymph nodes in patients with stage I or II melanoma.

PMID- 12185292
TI  - Coexistence of pregnancy and malignancy.
AB  - Cancer complicating pregnancy is a rare coexistence. The incidence is
      approximately 1 in 1,000 pregnancies. The most common cancers are those more
      frequently seen during the reproductive age of a woman. Breast cancer, cervical
      cancer, Hodgkin's disease, malignant melanoma, and leukemias are the most
      frequently diagnosed malignancies during gestation. The diagnostic and
      therapeutic management of the pregnant patient with cancer is especially
      difficult because it involves two persons, the mother and the fetus. In this
      paper we review: A) the therapeutic and diagnostic management of these patients;
      B) the safety of diagnostic and therapeutic procedures; C) the metastatic pattern
      of the maternal tumors to the placenta and fetus, and D) the potential
      recommendations for therapeutic abortion.

PMID- 12185293
TI  - Clinical studies of three oral prodrugs of 5-fluorouracil (capecitabine, UFT, S
      1): a review.
AB  - Although 5-fluorouracil (5-FU) was first introduced in 1957, it remains an
      essential part of the treatment of a wide range of solid tumors. 5-FU has
      antitumor activity against epithelial malignancies arising in the
      gastrointestinal tract and breast as well as the head and neck, with single-agent
      response rates of only 10%-30%. Although 5-FU is still the most widely prescribed
      agent for the treatment of colorectal cancer, less than one-third of patients
      achieve objective responses. Recent research has focused on the biomodulation of
      5-FU to improve the cytotoxicity and therapeutic effectiveness of this drug in
      the treatment of advanced disease. As all the anticancer agents, 5-FU leads to
      several toxicities. The toxicity profile of 5-FU is schedule dependent.
      Myelotoxicity is the major toxic effect in patients receiving bolus doses. Hand
      foot syndrome (palmar-plantar erythrodysesthesia), stomatitis, and neuro- and
      cardiotoxicities are associated with continuous infusions. Other adverse effects
      associated with both bolus-dose and continuous-infusion regimens include nausea
      and vomiting, diarrhea, alopecia, and dermatitis. All these reasons explain the
      need for more effective and less toxic fluoropyrimidines. In the first part of
      this review, we briefly present the metabolic pathways of 5-FU responsible for
      the efficacy and toxicity of this drug. This knowledge is also necessary to
      understand the target(s) of biomodulation. The second part is devoted to a review
      of the literature on three recent prodrugs of 5-FU, i.e., capecitabine, UFT
      (ftorafur [FTO] plus uracil), and S-1 (FTO plus 5-chloro-2,4-dihydroxypyridine
      plus potassium oxonate). The pharmacological principles that have influenced the
      development of these new drugs and our current knowledge of the clinical
      pharmacology of these new agents, focusing on antitumor activity and toxicity,
      are presented. The literature was analyzed until March 2002. This review is
      intended to be as exhaustive as possible since it was conceived as a work tool
      for readers wanting to go further.

PMID- 12185294
TI  - Weekly topotecan: an alternative to topotecan's standard daily x 5 schedule?
AB  - Relapsed ovarian cancer and small cell lung cancer are frequently treated with
      topotecan (Hycamtin), for which the standard dose and schedule are 1.5 mg/m(2)
      daily for five consecutive days every 3 weeks. Clinical experience has shown that
      this dose and schedule may be too toxic for some patients, especially those who
      have been heavily pretreated with platinum-based therapeutics, and it has been
      suggested that starting doses of topotecan be reduced to 1.0-1.25 mg/m(2)/d.
      Recently, multiple clinical trials have begun to evaluate the feasibility and
      preliminary antitumor activity of an alternative schedule based on weekly
      administration of topotecan. The potential benefits of weekly administration
      include not only reduced toxicity without significant compromise of antitumor
      activity, but also greater patient convenience and quality of life and greater
      potential for developing new topotecan-containing combination therapies. This
      report reviews the rationale for a weekly schedule, as well as a growing base of
      emerging clinical data. These preliminary data suggest that weekly topotecan is
      active; further evaluations are planned to confirm the activity and therapeutic
      index and to determine optimal dosing of a weekly schedule.

PMID- 12185295
TI  - Managing anemia in the cancer patient: old problems, future solutions.
AB  - Anemia and associated symptoms commonly manifest in cancer patients and may have
      a considerable impact on outcomes. Preliminary studies suggest that overall
      survival and locoregional control following radiation therapy may be compromised
      by anemia, and recent preliminary data also suggest that anemia may be related to
      poorer outcomes following chemotherapy. Health-related quality of life of cancer
      patients is also significantly reduced by anemia. Treatment of anemia with
      recombinant human erythropoietin can improve these health-related quality-of-life
      outcomes. However, despite this knowledge, anemia remains under-recognized and
      under-treated in the cancer patient population. A number of issues may be
      determinants of this suboptimal management of anemia. These include limitations
      of current therapies for anemia, varying practice strategies, and the lack of
      guidelines on how to treat anemia. Additionally, clinicians may underestimate the
      importance of health-related quality of life for their patients. It is vital that
      these issues are addressed, which, together with the development of novel
      erythropoietic agents, a review of the guidelines for anemia management, and
      consideration of further outcomes such as survival and cognitive function, may
      help to ensure that the cancer patient receives the best possible course of
      supportive care.

PMID- 12185297
TI  - The use of chemotherapy in soft-tissue sarcomas.
AB  - The treatment of advanced soft-tissue sarcomas is often palliative, although a
      subset of patients may be cured or have a long disease-free interval. This paper
      reviews the historical data over 30 years of treatment that has led to the use of
      ifosfamide and doxorubicin as the mainstay in the treatment of metastatic
      disease. These treatments have a high toxicity, relative to other
      chemotherapeutic regimens, with median response durations on the order of months.
      Agents developed in the last few years, whose role in the treatment of sarcomas
      is still evolving, are discussed as well. Finally, we discuss the role of
      chemotherapy in combination with surgery and radiation in the adjuvant and
      neoadjuvant settings.

PMID- 12185296
TI  - Guidelines for the treatment of recurrent and metastatic cervical cancer.
AB  - Although there have been important advances in the management of women with
      cervical cancer, the optimal treatment for patients with locally recurrent and
      metastatic disease is still problematic, and there are relatively few randomized
      trials to guide treatment decisions. This paper reviews the approach to
      management of patients who relapse after primary treatment for cervical cancer.
      Patients who are still potentially curable with radical treatment are identified,
      and the various treatment strategies are discussed. However, most women are
      treated with palliative intent, and the literature on palliative management is
      reviewed together with the levels of evidence.

PMID- 12185298
TI  - State-of-the-art treatment of metastatic hormone-refractory prostate cancer.
AB  - Initial therapy for advanced prostate cancer includes androgen ablation by
      surgical or medical castration. Still, nearly all men with metastases will
      progress to hormone-refractory prostate cancer (HRPC). Current U.S. Food and Drug
      Administration-approved agents for the treatment of HRPC include mitoxantrone and
      estramustine, although the vinca alkaloids and the taxanes have shown promising
      activity in single-agent phase II trials. Combinations of these agents induce a
      biochemical response in greater than 50% of patients, but the median duration of
      response is approximately 6 months. Overall survival of patients treated with
      these combinations is approximately 18-24 months. Studies are ongoing to develop
      novel therapies that target specific molecular pathways or mechanisms of
      chemotherapy resistance. Novel agents under development include growth factor
      receptor inhibitors, antisense oligonucleotides, bisphosphonates, and cell
      differentiating agents. Evaluation and incorporation of these agents into
      existing treatment regimens will guide us in the development of more active
      regimens in the treatment of HRPC.

PMID- 12185299
TI  - Faith, identity, and leukemia: when blood products are not an option.
AB  - Shortly before his death in 1995, Kenneth B. Schwartz, a cancer patient at
      Massachusetts General Hospital, founded the Kenneth B. Schwartz Center. The
      Schwartz Center is a non-profit organization dedicated to supporting and
      advancing compassionate health care delivery, which provides hope to the patient,
      support to caregivers, and sustenance to the healing process. The center sponsors
      the Schwartz Center Rounds, a monthly multidisciplinary forum where caregivers
      reflect on important psychosocial issues faced by patients, their families, and
      their caregivers and gain insight and support from fellow staff members. When a
      competent adult patient refuses lifesaving treatment for religious or personal
      reasons, caregivers have a legal obligation to respect this decision. A patient's
      refusal of treatment adds particular challenges to the delivery of compassionate
      care. The case of a 50-year-old Jehovah's Witness with acute myelocytic leukemia
      who declined blood product support is presented. Respecting her religious beliefs
      during chemotherapy required balancing risk and benefit, watching her suffer
      while unable to intervene with what the staff saw as simple treatment, and
      eventually undertaking a complicated grief process. Jehovah's Witness beliefs
      regarding blood products are reviewed. Caregiver roles and responsibilities are
      discussed in the context of psychosocial, legal, familial, and ethical issues.

PMID- 12185300
TI  - The molecular perspective: DNA topoisomerases.

PMID- 12185301
TI  - Trust factor.

PMID- 12185302
TI  - The person with cancer and quality of life.

PMID- 12185305
TI  - Lectin-binding characteristics and capacitation of canine epididymal spermatozoa.
AB  - Cross sections of the testes and the caput, corpus and cauda epididymides removed
      from 12 dogs were stamped on glass slides, and the sperm on the slides were
      stained with 6 different FITC-lectins (Con A, DBA, PNA, PSA, SBA, and WGA) to
      examine the characteristics of the surface glycoproteins (GPs) on canine
      epididymal sperm. The corpus epididymal sperm were washed three times by
      centrifugation, and their lectin-binding characteristics were investigated. The
      washed sperm from the corpus and cauda epididymides were incubated for 24 hr, and
      the fertilizing capacity of the sperm was evaluated by calculating the
      percentages of actively motile sperm (%MO), hyperactivated sperm (%HA), and
      acrosome-reacted sperm (%AR), and the number of canine zona-pellucida (ZP)
      binding sperm. The testicular sperm did not stain with SBA lectin, but the SBA
      lectin fluorescence was observed on the surface of the entire heads of the caput
      epididymal sperm. Although all of the entire heads or acrosomal regions of the
      corpus epididymal sperm stained with all 6 FITC-lectins, the heads and acrosomal
      regions of the cauda epididymal sperm did not stain with DBA or SBA lectins.
      Washing the sperm from the corpus epididymis resulted in loss of the fluorescence
      of the FITC-DBA and -SBA lectins. The mean %MO, %HA, %AR, and ZP-binding number
      of the cauda epididymal sperm after 24 hr of incubation were higher than the
      values for the corpus epididymal sperm. All of the mean values for the washed
      sperm from the corpus and cauda epididymides were higher than the values for the
      unwashed sperm from the corpus and cauda, and with the exception of %AR, the
      values from the washed sperm from the corpus epididymis were significantly higher
      (P<0.05, 0.01). The results indicate that DBA- and SBA-lectin-binding GPs on the
      surface of canine epididymal sperm are associated with the fertilizing capacity
      and may be decapacitation factors.

PMID- 12185306
TI  - Susceptibility of liver proliferative lesions in heterozygous p53 deficient CBA
      mice to various carcinogens.
AB  - To investigate the liver tumorigenic sensitivity to various carcinogens in
      heterozygous p53 deficient [p53 (+/-)] CBA mice and their wild-type littermates
      [p53 (+/+) mice], 71 p53 (+/-) and 74 p53 (+/+) CBA mice (male, 6-12 weeks of
      age) were given diet containing 4,000 or 0 ppm flumequine (FL) for 26 weeks or a
      single intraperitoneal injection of 5 mg/kg body weights dimethylnitrosamine
      (DMN) at start of the study in Exp. 1, diet containing 6,000 or 0 ppm di(2
      ethylhexyl)-phthalate (DEHP) for 26 weeks in Exp. 2, or diet containing 12,000,
      6,000 or 0 ppm phenolphthalein (PhP) for 26 weeks in Exp. 3. All surviving
      animals of these groups were killed after completion of treatment of the test
      substances for 26 weeks. In the FL groups, the incidences of hepatocellular
      altered foci in p53 (+/-) mice, the multiplicities of those in p53 (+/-) and p53
      (+/+) mice were significantly increased as compared to the corresponding control
      groups. The incidences and multiplicities of altered foci in the DMN groups were
      higher than those in the corresponding control groups in p53 (+/-) and p53 (+/+)
      mice, but no significant differences were indicated between the groups. There
      were no significant differences in the incidences, multiplicities and
      proliferating cell nuclear antigen labeling indices of altered foci in the FL or
      DMN groups between p53 (+/-) and p53 (+/+) mice. There were no significant
      differences in the incidences and multiplicities of altered foci between the DEHP
      or PhP and control groups. The present results suggest that p53 gene knocked out
      heterozygously does not enhance the chemical hepatocarcinogenesis in CBA mice.

PMID- 12185307
TI  - The metabolic profile test: its practicability in assessing feeding management
      and periparturient diseases in high yielding commercial dairy herds.
AB  - The aim of this study was to evaluate the practicability of using the metabolic
      profile test (MPT) as a preventive tool for periparturient disease of dairy cows.
      The MPT was assessed in 79 dairy herds with high incidence of periparturient
      disease and 76 healthy herds of cows producing more than 8,500 kg 305-day milk
      yield. The changes in metabolic profiles were also assessed in 17 dairy herds at
      two times, the first at high incidence of periparturient disease and the second
      after reduced incidence and improved feeding management. In the herds with high
      incidence of periparturient disease, low blood values of hematocrit, albumin,
      glucose, cholesterol, calcium and magnesium were observed in the dry period.
      These values correctly diagnosed malnutrition as the cause of periparturient
      diseases. Following feeding management changes, there was a low incidence of
      periparturient disease and the metabolic profiles were normal showing that
      feeding management had improved. We concluded that the MPT is a useful tool for
      assessing feeding management and periparturient diseases of dairy cows.

PMID- 12185308
TI  - Fecal progesterone analysis by time-resolved fluoroimmunoassay (TR-FIA) for
      monitoring of luteal function in the sika doe (Cervus nippon centralis).
AB  - Fecal progesterone content was measured by time-resolved fluoroimmunoassay (TR
      FIA) in the sika doe (Cervus nippon). The total recovery rate of fecal
      progesterone by twice extraction with diethylether was about 60%. The
      displacement curve of TR-FIA with serial doses of fecal extract (0.156-5.0 mg
      feces) was closely parallel to that of the reference standard. Fecal progesterone
      content was correlated with that of plasma (r=0.829, n=16), but the values were
      100-fold higher in feces than in plasma. Fecal progesterone content periodically
      changed during the breeding season suggesting the estrous cycle in the doe. The
      fecal progesterone content was higher between the estruses, and decreased after
      estrus. The time between the onset of estrous signs and the lowest fecal
      progesterone content was 1-2 days suggesting the time required for hepatic
      metabolism and intestinal passage. Fecal progesterone content was also decreased
      around the time of vaginal discharge. The discharge took place within a few days,
      suggesting a short luteal phase. Not of all decreases in fecal progesterone
      values were preceded by estrous behavior or vaginal discharge. Fecal progesterone
      content was further increased in pregnancy rather than in the preceding estrous
      cycle and the levels were maintained up to term. These results suggest that fecal
      progesterone measurement is a useful tool for non-invasive analysis of luteal
      function in the sika doe. The TR-FIA kit, designed for the human hospital market,
      was shown to be successfully utilized for fecal assay in the sika doe with minor
      modifications.

PMID- 12185309
TI  - Continuous in vitro culture of erythrocytic stages of Babesia gibsoni and
      virulence of the cultivated parasite.
AB  - Babesia gibsoni infected erythrocytes were collected from the blood of an
      experimentally infected dog. The parasite isolated could be continuously
      cultivated in vitro, with an average parasitemia of 18.2 +/- 2.4% on day 3 of
      culture, in RPMI-1640 medium supplemented with 7.5% normal dog serum in a
      humidified atmosphere containing 5% CO(2) at 37 degrees C. The parasites in the
      original culture were morphologically similar to those found in the peripheral
      blood of dogs, however, on the 4th generation of subculture, the large oval
      parasites, erythrocytes including many parasites and extracellular parasites were
      frequently observed. The B. gibsoni isolate was injected to the dog to test its
      infectivity after maintained in vitro for 738 days at the 214th subculture. The
      cultivated parasite did not cause a severe clinical sign in the dog.

PMID- 12185310
TI  - Magnetic resonance imaging application to live horse for diagnosis of tendinitis.
AB  - Six live horses with various stages of acute to chronic superficial digital
      flexor (SDF) tendinitis were examined using magnetic resonance imaging (MRI). In
      each case, MRI findings were compared to the corresponding ultrasonographic (USD)
      and histologic findings, to establish the usefulness of MRI. In the acute cases,
      lesions characterized by hemorrhage were well defined as high signal intensity on
      MRI and hypoechoic regions on USD. Chronic tendon fibrosis was slightly
      hyperechoic and difficult to distinguish from the normal tendon tissue around the
      original injury by using USD. In contrast, MRI visualized the chronic lesion as a
      low intensity signal, which could be distinguished from the black background of
      the normal SDF tendon tissue. This study clearly demonstrated MRI was the better
      imaging modality for the objective detection of chronic scar tissue in live
      horses. These findings, from living horses, suggest an advantage of MRI in the
      clinical application to diagnose tendinitis in cases where there is chronic scar
      tissue that is difficult to discern on USD.

PMID- 12185311
TI  - Evaluation of enzyme-linked immunosorbent assay (ELISA) and immunofluorescent
      antibody (IFA) test for the detection of porcine reproductive and respiratory
      syndrome virus (PRRSV) antibody in pigs from conventional farms.
AB  - To evaluate the immunofluorescent antibody (IFA) test and enzyme-linked
      immunosorbent assay (ELISA) for detecting the porcine reproductive and
      respiratory syndrome virus (PRRSV) antibody, conventional pigs in PRRSV-positive
      and -negative commercial farms were examined. Antibody development patterns in
      ELISA and IFA tests were compared in 3 week old piglets experimentally infected
      with the PRRSV. The virus was detected from 2 days post infection (PI) and then
      the antibody titers and S/P ratios rose by both methods. A total of 208 serum
      samples were collected from 4 PRRSV-negative farms and 210 samples from PRRSV
      positive farms, and were tested for the PRRSV antibody by IFA and ELISA. The
      titer of 64 should be set as the cut-off point in IFA for field sera. Similarly,
      the cut-off S/P ratio should be set at 0.4 in ELISA. A high degree of correlation
      was observed between antibody titers by the two methods in these 418 samples,
      with a correlation coefficient of 0.84. The coincidence rate between the two
      tests was 84.7% (354/418). In non-coincident cases, ELISA was able to detect the
      antibody with a low titer in the serum samples which were negative in IFA but
      from PRRSV positive farms. ELISA was more sensitive than IFA to detect PRRSV
      infected animals or farms.

PMID- 12185312
TI  - Bovine herpesvirus-1 (BHV-1) recombinant expressing pseudorabies virus (PrV)
      glycoproteins B and C induces type 1 immune response in BALB/c mice.
AB  - Bovine herpesvirus 1 (BHV-1) attached poorly and penetrated into a mouse cell
      line, BALB 3T3/A31, but a recombinant BHV-1/TF7-6, which expresses pseudorabies
      virus (PrV) gB and gC genes, did attach and penetrated into cells more
      efficiently. In this study the gene green fluorescent protein (GFP) has been
      integrated into genome of BHV-1/TF7-6 and its parental line of BHV-1. When the
      mouse mesenteries were incubated in vitro and infected with BHV-1/TF7-6/GFP,
      strong fluorescence was observed while BHV-1/GFP infection hardly demonstrated
      fluorescence, suggesting that BHV-1 recombinant expressing PrV gB and gC can
      infect mouse tissue cells more efficiently than the parental BHV-1 does. When
      BALB/c mice were inoculated with purified BHV-1/TF7-6 or its parental BHV-1, the
      former induced lower level of anti-BHV-1 immunoglobulin G (IgG) than the latter
      did. When sub-classes of anti-BHV-1 IgG were analyzed, it was found that mice
      immunized with BHV-1/TF7-6 or the parental BHV-1 demonstrated the same level of
      IgG2a. Since anti-BHV-1 IgG1 level was lower in mice inoculated with BHV-1/TF7-6,
      the IgG2a:IgG1 ratio was higher in BHV-1/TF7-6 inoculated mice than in the
      parental BHV-1 inoculated ones. These results indicate that BHV-1/TF7-6 induces
      type 1 predominant immune to BALB/c mice.

PMID- 12185313
TI  - High sensitivity of thymocytes of LEC strain rats to induction of apoptosis by X
      irradiation.
AB  - It is known that physical disruption of cell contacts induces apoptosis of
      thymocytes. When thymocytes from LEC and WKAH rats were incubated in vitro at 37
      degrees C for 0-6 hr and then the proportion of apoptotic cells was determined
      using a flow cytometer, it was found that the percentages of apoptotic thymocytes
      from both LEC and WKAH rats increased with incubation time and that the
      proportion of apoptotic cells from LEC rats was significantly higher than that
      from WKAH rats at each incubation time. The fact that cycloheximide, an inhibitor
      of protein synthesis, did not show significant inhibitory effects on induction of
      apoptosis of thymocytes indicates that induction of apoptosis during in vitro
      cultivation did not require de novo protein synthesis. When thymocytes from LEC
      and WKAH rats were X-irradiated in vitro at 4 and 8 Gy, the percentages of
      radiation-induced apoptotic cells increased with post-incubation time after X
      irradiation in both LEC and WKAH rat thymocytes and the proportions of apoptotic
      cells from LEC rats were significantly higher than those from WKAH rat cells at 2
      and 4 hr post-incubation after X-irradiation. When thymocytes from LEC and WKAH
      rats were X-irradiated in the presence of cycloheximide, the induction of
      apoptosis was substantially inhibited, indicating that radiation-induced
      apoptosis of thymocytes from LEC and WKAH rats required de novo protein
      synthesis. The present results showed high sensitivities of thymocytes of LEC
      rats to induction of apoptosis during in vitro cultivation and by X-irradiation.

PMID- 12185314
TI  - Development of a PCR test for the identification of Staphylococcus intermedius
      based on the 16S rDNA sequence.
AB  - The development of a PCR assay based on the 16S ribosomal RNA gene (rDNA)
      sequence was carried out for the identification of Staphylococcus intermedius.
      Sixty-six strains of S. intermedius, 70 of Staphylococcus aureus and 2 of
      Staphylococcus hyicus were examined for the assay. The 16S rDNA, of which the PCR
      target fragment makes up 901 bp corresponding to the sequence data of the gene,
      was detected in all strains of S. intermedius, but it was not detected in any
      strains of either S. aureus or S. hyicus. These results suggest that the PCR
      allows a simple and precise identification of S. intermedius.

PMID- 12185316
TI  - A canine case of gliosis with cyst formation in the posterior fossa.
AB  - A 5-month-old male Great Pyrenees with symptoms of convulsions, circling, and a
      head tilt was referred to the Animal Medical Center of Nihon University. On a
      magnetic resonance image (MRI), a cyst in the posterior fossa was noted and a
      part of the cyst enhanced by gadoteridol. Based on MRI and clinical findings, the
      patient was tentatively diagnosed with a cyst formation tumor, and an operation
      to open the cyst and remove the part enhanced by contrast was performed.
      Postoperatively, the clinical course was good. Pathologically, the removed tissue
      was diagnosed as a gliosis with cyst formation.

PMID- 12185317
TI  - Tick infestation of sika deer (Cervus nippon) in the western part of Yamaguchi
      Prefecture, Japan.
AB  - Ticks were collected from 94 sika deer (Cervus nippon) hunted in the western part
      of Yamaguchi Prefecture, Japan from August to November 1999, and March to July
      2000. Haemaphysalis longicornis and H. yeni were the dominant species from April
      to August, while H. flava and H. megaspinosa were dominant in October, November
      and March. This is the first report of H. yeni in the mainland of Japan. Small
      numbers of H. kitaokai, Amblyomma testudinarium and Ixodes ovatus were also
      recorded.

PMID- 12185315
TI  - Concentrations of toxic metals and essential minerals in the mane hair of healthy
      racing horses and their relation to age.
AB  - Concentrations of trace elements (As, Al, Pb, Cd, Hg, Se, Si, P, Na, K, Ca, Mg,
      Fe, Cu, Zn, Mn, Cr, Ni and Mn) in the mane hair obtained from 9 female and 15
      male healthy racing Thoroughbred horses aged 2-5 years were analyzed by the
      inductively coupled plasma atomic emission spectrometry (ICP-AES) method. No
      significant differences between the female and male horses were observed in the
      mean concentrations of those minerals. Significantly positive correlations with
      age were observed in Cd (r=0.546, p<0.01) and Mo (r=0.733, p<0.001).
      Significantly negative correlations with age were observed in Hg (r= -0.726,
      p<0.001), Mn (r= -0.450, p<0.05) and Fe (r=-0.642, p<0.01). This reference range
      of trace elements in the mane hair of racing horses should be used to assess
      disease and the nutritional status in equine practice.

PMID- 12185318
TI  - Hypertrophic cardiomyopathy in a mixed breed cat family.
AB  - A spayed female mixed cat (case 1) and its female offspring, the result of a
      pairing between case 1 and its male sibling, were diagnosed with hypertrophic
      cardiomyopathy (HCM). A pedigree survey revealed that the prevalence of HCM was
      at least 12.5% in the family, which was considered to be significantly higher
      than that in a hospital-based population (approximately 1.6%). Thus, this finding
      seems to support the suspected occurrence of familial HCM in this group of
      related cats.

PMID- 12185319
TI  - Increase in oxidized proteins in Theileria sergenti-infected erythrocyte
      membrane.
AB  - As a part of the elucidation of the pathogenesis of anemia in Theileria sergenti
      infection, oxidized-erythrocyte membrane proteins (OEMPs) collected from T.
      sergenti-infected calves were examined. The amount of OEMPs were seen to increase
      with the progress of the anemia and showed a maximum value around the crisis
      period of the infection. The increase of OEMPs coincided with band Nos. 1, 2,
      2.1, 3, 4.1, 5, 6, and 7. The majority of them was located at the Triton X-100 un
      extractive phase, and was confirmed as cytoskeletal proteins. This evidence
      indicates the enhancement of erythrocytic oxidation, and suggests that it might
      be one of the aggravating factors of anemia in T. sergenti infection.

PMID- 12185320
TI  - The immediate early gene of canine herpesvirus is transcribed through early and
      late phases.
AB  - The immediate early (IE) gene of canine herpesvirus (CHV), homologue of the
      infected cell protein 4 (ICP4) gene of herpes simplex virus 1, is transcribed as
      a 4.9kb mRNA during IE phase. The IE gene was further transcribed as a 4.8kb mRNA
      through early (E) and late (L) phases of productive infection. Transcription of
      the 4.8kb mRNA initiated from downstream of the TATA box in an intron which was
      spliced out during IE phase. The reverse transcription-polymerase chain reaction
      revealed that the IE promoter was turned off during L phase at a permissive
      temperature. We, thus, propose to redesignate the IE gene of CHV as CICP4 gene.

PMID- 12185321
TI  - Intestinal spirochetosis in a 21-month-old thoroughbred colt.
AB  - A 21-month-old Thoroughbred colt showed continuous diarrhea and developmental
      retardation for 7 months, and was thereafter subjected to euthanasia for necropsy
      and laboratory examinations. At necropsy, the cecal and colonic mucosae were
      diffusely rough and hyperemic. Histopathologically, the mucosa and submucosa were
      edematous and were infiltrated by numerous lymphocytes and macrophages.
      Meanwhile, three morphological types of Brachyspira antigen-containing
      spirochetes were found to be numerous in the crypts and in the mucus layer over
      the epithelium in the cecal and colonic lesions. They were frequently observed in
      intercellular gaps and in the cytoplasm of degenerative epithelial cells, and in
      the lamina propria, particularly in cavities around blood vessels. These invasive
      intestinal spirochetes might be one of pathogens inducing colitis and diarrhea in
      horses.

PMID- 12185322
TI  - Thymoma and multiple thymic cysts in a dog with acquired myasthenia gravis.
AB  - An anterior mediastinal cystic lesion in an 11-year-old mongrel dog was examined.
      The dog showed dysbasia and vomiting due to megaoesophagus, and anterior
      mediastinal round mass lesion, approximately 35 mm in diameter, was found by X
      ray. Based on clinical examinations, the dog was diagnosed as acquired myasthenia
      gravis and was successfully controlled by anticholinesterase treatment for
      approximately 4 months. The dog died of thermic stroke and was necropsied.
      Grossly, fatty tissues with cysts containing yellowish fluid and white nodules
      were found in the anterior mediastinal area. Histopathologically, multiple cysts,
      neoplastic tissues, and atrophic thymus were found within the examined tissues.
      The cysts were lined by thin wall consisting of ciliated long cuboidal and non
      ciliated round cells and were filled with eosinophilic colloidal fluid. Some
      extended cysts contained neoplastic foci within their lumen and walls. The
      neoplastic tissues consisted of mixed population of large epithelial cells with
      abundant clear cytoplasm and large oval nuclei, and lymphocytes.
      Immunohistochemically, proliferating epithelial cells were intensely positive for
      keratin and cytokeratin, and more than half number of infiltrating lymphocytes
      were intensely positive for CD3 suggesting T cells. All these findings indicate
      the neoplastic lesion is thymoma and multiple cysts are considered as thymic or
      brachial cleft cysts.

PMID- 12185323
TI  - Parathyroid hormone induces interleukin-6 gene expression in bone stromal cells
      of young rats.
AB  - To test the hypothesis that parathyroid hormone (PTH) regulates interleukin-6 (IL
      6) expression locally in bone, the expression of IL-6 mRNA was examined by in
      situ hybridization after a subcutaneous injection of human PTH [1-84] (225
      microg/kg) in 4-week old rats. Whereas IL-6 mRNA was not detected at the basal
      status, it was transiently detected in a subpopulation of stromal cells in the
      intertrabecular region of the metaphyses from 1/2 to 1 hr after PTH injection.
      Contrastingly, IL-6 transcripts were not detected in other cell populations at
      any time points examined. Since IL-6 is a known activator of osteoclasts, these
      results are consistent with the hypothesis that PTH stimulates the local IL-6
      synthesis in stromal cells to indirectly activate osteoclasts.

PMID- 12185324
TI  - Chitosan and D-glucosamine induce expression of Th1 cytokine genes in porcine
      spleen cells.
AB  - Chitosan, a polymer of D-glucosamine, is a polysaccharide derived from the chitin
      found in the exoskeleton of shellfish, such as shrimp or crabs. The effects of
      chitosan has been recognized that chitosan-fed farm animals demonstrated higher
      weight gains but less incidence of diseases than the unfed ones. However, these
      beneficial effects has not been elucidated clearly. In this study, we examined
      the modulatory effect of chitosan and D-glucosamine on the expression of porcine
      cytokines in vitro. Porcine spleen cells were cultured in the presence of
      chitosan and D-glucosamine, and the effects of chitosan on the cytokine mRNA
      expression were evaluated. Expressions of IL-2 and IFN-gamma were increased in
      the chitosan-treated porcine spleen cells. Expressed cytokines in the D
      glucosamine-treated cells were IL-2, IFN-gamma, and IL-12 p40 subunit. In
      particular, IFN-gamma was expressed more efficiently, and D-glucosamine was more
      effective for expressing the cytokine gene. These results suggest chitosan as
      well as D-glucosamine could induce the expression of cytokines as Th1 subset such
      as IL-2, IFN-gamma.

PMID- 12185325
TI  - Implantation of VX2 carcinoma into the liver of rabbits: a comparison of three
      direct-injection methods.
AB  - The efficacy of agarose in preventing VX2 carcinoma cell leakage was evaluated
      and the results were compared with two traditional methods. Forty-five rabbits
      were divided into 3 groups: Group 1, VX2 tumor cells were injected directly into
      the liver and no special procedure after removal of the needle; Group 2, the
      puncture site was gently compressed, using an alcoholic cotton gauze, for three
      minutes; Group 3, 0.2 ml of heated liquid agarose was injected to seal the
      aperture after injection of VX2 cells. The leakage rates were 80%, 53.3% and 6.6%
      for group 1, group 2 and group 3, respectively. We consider agarose is a useful
      material in preventing the leakage in the establishment of VX2 liver tumor
      models.

PMID- 12185326
TI  - Serum activities of tartrate-resistant acid phosphatase and bone specific
      alkaline phosphatase as indices of bone metabolism in the cow.
AB  - The correlation between the serum hydroxyproline concentration and serum activity
      levels of TRAP and BALP was examined in 41 cows. The correlated coefficient (r)
      was 0.6391 for TRAP and 0.3147 for BALP, respectively. Judging from the
      significant correlation to the serum hydroxyproline concentration, serum TRAP
      activity is an index for bone metabolism in cows. Serum TRAP activity was
      therefore measured in 205 healthy cows (2-9 years old) in order to observe the
      changes in bone resorption with aging and milk production. TRAP levels differed
      slightly between group A (< or =4 yrs) and B (5 yrs< or =) at the same stage of
      lactation. The activity levels rose slightly at the height of lactation stage and
      during the dry stage.

PMID- 12185327
TI  - Adjuvant hormonal therapy.
AB  - Recently, the guidelines for adjuvant hormonal therapy for primary breast cancer
      were presented at the National Institute of Health Consensus Development
      Conference in November 2000 and at the 7th International Conference on Adjuvant
      Therapy of Primary Breast Cancer in February 2001. Adjuvant hormonal therapy
      should be offered basically to all patients with tumors expressing estrogen
      receptor (ER) and/or progesterone receptor (PR), assessed by
      immunohistochemistry. The consensus statements recommended 5 years of tamoxifen
      as standard hormonal therapy for both premenopausal and postmenopausal patients
      with ER and/or PR positive tumors. Ovarian ablation or suppression of ovarian
      function combined with tamoxifen is a treatment of choice for premenopausal
      patients with high-risk endocrine-responsive tumors. The selection of hormonal
      therapies and their combination with chemotherapy should be decided according to
      the assessment of risk of relapse, side effects, and patients' condition and
      preference.

PMID- 12185328
TI  - Adjuvant radiation therapy following mastectomy for breast cancer.
AB  - Many randomized clinical trials have been performed to address the effectiveness
      of postmastectomy radiation therapy (PMRT) to regional lymph nodes with or
      without chest wall irradiation. Although these studies have confirmed the
      usefulness of RT to reduce loco-regional recurrence, the benefit of postoperative
      RT for survival remains controversial. Recent prospective trials of PMRT in
      combination with systemic chemotherapy clearly demonstrated the benefit of this
      combined adjuvant therapy for both locoregional recurrence and survival outcomes.
      Based upon this new evidence, guidelines and recommendations for PMRT in the
      management of breast cancer have been proposed by the American Society of
      Clinical Oncology and by the International Consensus Panel at the International
      Conference on Adjuvant Therapy of Primary Breast Cancer in St. Gallen. PMRT is
      recognized as a standard adjuvant treatment for patients with more than 4
      positive axillary nodes in these guidelines and recommendations. This re
      appraisal of PMRT has not attracted much attention in Japan so far. Clinical
      studies are needed to determine how to best incorporate PMRT in the multimodal
      treatment of node-positive breast cancer.

PMID- 12185329
TI  - Systematic overview of quality of life studies for breast cancer.
AB  - BACKGROUND: The concept of quality of life (QOL) is essentially subjective,
      determined from the patient's point of view. Thus, an appropriate investigation
      and analysis of QOL as an indicator of medical treatment outcome is a task of
      some difficulty. The physician-led QOL assessment studies to date in Japan have
      suffered from insufficient knowledge and understanding of the diverse factors
      contributing to QOL, thereby contributing to a dearth of quality studies. Given
      this background, the Japanese Breast Cancer Society has established a Task Force
      for the development of guidelines to properly conduct QOL assessment studies. The
      present article reports the results of a large-scale systematic overview of QOL
      assessment studies for breast cancer patients that was undertaken as one part of
      this project. METHODS: Six databases were used in this overview: MEDLINE, CINAHL,
      CANCERLIT, EMBASE, PsychINFO, and Japan Centra Revuo Medicina. The search period
      was 1982-1999 for CINAHL, and 1990-1999 for the others. Following a check of the
      titles, important information was recorded on relevance and data collection
      forms. RESULTS: A systematic search was conducted of the literature on QOL
      assessment studies for breast cancer patients, and 1,954 articles were extracted
      from a check of titles. Using the relevance and data collection forms, the number
      of articles was further narrowed to 126. These articles were then classified
      according to the type and design of the study, the number of QOL and
      psychological measures used, frequency of use of each measure, and study focus
      and type of intervention. The results were then compiled. CONCLUSION: To date
      there have been almost no appropriate systematic overviews or guidelines issued
      for QOL assessment studies related to breast cancer, even on the international
      level. The results of the present study may contribute high-quality QOL
      information for evidence-based medicine, as it continues to gain global
      prevalence.

PMID- 12185330
TI  - Importance of the retro-mammary space as a route of breast cancer metastasis.
AB  - BACKGROUND: There are many cases of breast cancer with axillary lymph node
      metastases without lymphatic invasion. We hypothesized that in these cases cancer
      cells may pass through the retro-mammary space (RS) into lymph nodes and that
      axillary lymph node metastases may correlate with the tumor invasion of the RS.
      METHODS: A total of 127 patients who had undergone radical operation between
      April 1997 and April 2001 were studied. Whether or not the tumor had invaded the
      RS was histologically examined with hematoxylin and eosin staining of sections
      made at the point where the distance between the tumor and the fascia of the
      major pectoral muscle was the shortest. RESULTS: Eighty-five cases did not have
      lymphatic invasion. Twenty-nine of these 85 cases had RS invasion and 56 cases
      did not. Among the 29 cases with RS invasion, 14 cases had lymph node metastases.
      In contrast, of 56 cases without RS invasion only 3 cases had lymph node
      involvement. Of the 85 cases without lymphatic invasion, the relationship between
      RS invasion and lymph node invasion was statistically significant (RS(+) vs. RS(
      ), p<0.0001, chi-square test). For all 127 cases, if cases showing either
      lymphatic invasion or RS invasion were diagnosed with lymph node involvement, the
      sensitivity, specificity, accuracy, and negative predictive value were 93.5%,
      65.4%, 75.6% and 94.6%, respectively. CONCLUSION: These data suggest that lymph
      node metastases may occur via the tumor cell migration through lymphatic vessels
      and the RS.

PMID- 12185332
TI  - p63 expression in normal, hyperplastic and malignant breast tissues.
AB  - BACKGROUND: p63 is a homologue of the p53 tumor suppressor gene and its protein
      is selectively expressed in the basal cells of a variety of epithelial tissues.
      It has recently been confirmed that p63 is expressed in the basal cells of normal
      prostate glands but not in prostatic carcinomas. Whether expression of p63 in
      breast correlates with tumor progression is the focus of this study. METHODS:
      Forty cases, which all contained normal breast tissue, ductal hyperplasia, ductal
      carcinoma in situ and invasive ductal carcinoma in the same patient were included
      in this investigation using an indirect immunohistochemical method and double
      staining. RESULTS: p63 was exclusively expressed in the myoepithelial cells of
      normal breast, partially expressed in ductal hyperplasia, rarely expressed in
      carcinoma in situ and not expressed in invasive carcinomas. CONCLUSION: The
      results suggest an association between loss of p63 expression and progression of
      breast ductal carcinoma. p63 immunostaining might be of assistance for
      distinguishing invasive ductal carcinoma from ductal carcinoma in situ or rare
      questionable ductal hyperplastic lesions, leading to correct therapy clinically.

PMID- 12185331
TI  - Correlation of allelic losses and clinicopathological factors in 504 primary
      breast cancers.
AB  - BACKGROUND: We have defined 18 chromosomal regions in which allelic losses were
      frequent among breast cancers. We examined whether specific allelic losses might
      correlate with any clinicopathological factors. METHODS: We tested DNA from
      matched normal and tumor tissues for loss of heterozygosity (LOH) at 18
      microsatellite loci from a cohort of 504 patients who had undergone surgery for
      breast cancer. RESULTS: LOH at 3p14.3 correlated with a larger size of tumor
      (greater than 2 cm). LOH at 1p22, 3p25.1, 3p14.3, or 17q21.1 correlated with loss
      of estrogen receptors. LOH at as many as eleven regions correlated with loss of
      progesterone receptor, suggesting that these represent general phenomena
      associated with progression of cancer. Above all, allelic losses at 11q23-24,
      13q12, 17p13.3, or 22q13 significantly correlated with lymph-node metastasis
      (11q23-24, p= 0.0042; 13q12, p=0.0207; 17p13.3, p=0.0478; 22q13, p=0.0162).
      CONCLUSION: These results suggest that some clinical characteristics of breast
      cancers are determined by loss of tumor suppressor genes present at specific
      chromosome regions. Especially, LOH at 11q23-24, 13q12, 17p13.3, and 22q13 is a
      significant predictor of lymph-node metastasis for patients who have undergone
      surgery for breast cancer, and may serve as a negative prognostic indicator.

PMID- 12185333
TI  - Endoscopic classification of intraductal lesions and histological diagnosis.
AB  - BACKGROUND: To diagnose intraductal lesions endoscopically the Japanese
      Association of Mammary Ductoscopy classified the endoscopical appearance of
      lesions into three types. We investigated the correlation between endoscopic
      classification and histological diagnosis. METHODS: From April 1998 to February
      2001, we enrolled 129 female patients who were diagnosed histologically and whose
      intraductal lesions were detected by mammary ductoscopy. The endoscopic
      classification consists of three types. The polypoid type is a localized
      expansive lesion. This type is divided into two subtypes, the solitary subtype
      (solitary polypoid lesion) and the multiple subtype (multiple polypoid lesions).
      The combined type is polypoid lesion(s)coexisting with a superficial type. The
      superficial type is a superficial spreading lesion such as a continuous luminal
      irregularity accompanied by no obvious elevations. RESULTS: There were 65 cases
      of breast cancer and 64 cases of benign papillary lesions. Fifty-four cases of
      benign papillary lesions and 7 cases of breast cancer were classified as the
      polypoid-solitary type. Seven benign cases and 13 cases of cancer were classified
      as the polypoid-multiple type. Two benign cases and 16 cases of cancer were
      classified as the combined type. Only one benign case and 29 cases of cancer were
      classified as the superficial type. There is significant correlation between
      endoscopical types and the histological diagnosis (p<0.0001). CONCLUSIONS:
      Endoscopic classification is useful to diagnose intraductal lesions.

PMID- 12185334
TI  - Dynamic-enhanced MRI predicts metastatic potential of invasive ductal breast
      cancer.
AB  - BACKGROUND: Dynamic magnetic resonance imaging (MRI) has improved the detection
      of breast malignancies. The method is based on estimating the velocity of
      contrast enhancement taking into account increased angiogenesis in tumor.
      Microvessel density correlates with breast carcinoma metastasis. Thus, we
      hypothesized that contrast enhancement on MRI correlates with metastasis in
      breast cancer patients. The present study attempts to clarify the quantitative
      assessment of dynamic data, and examines the correlation between MRI enhancement
      and breast carcinoma metastasis. METHODS: The subjects consisted of 31 patients
      with invasive ductal breast cancer. Twenty patients were disease free for five
      years (group A), and eleven patients suffered from metastatic disease at distant
      sites concurrently or postoperatively (group B). Dynamic MRI was performed
      preoperatively using a 1.5T system in all cases. Using the dynamic data, the
      signal intensity (SI)ratio and SI index were determined and analyzed
      retrospectively taking into account the presence of distant metastases. RESULTS:
      The values of the SI ratio were 2.2+/-0.7 in group A and 2.3+/-0.4 in group B,
      respectively, with no significant difference seen between the groups. The SI
      index value was significantly higher in group B (28.5+/-32.8) than in group A
      (10.3+/-5.5, p<0.05). CONCLUSIONS: The current series suggests that the SI index
      could distinguish patients with high risk of distant metastasis from disease free
      patients, preoperatively. If a suitable borderline value were established, the
      quantitative dynamic parameter determined by MRI may be useful for predicting the
      prognosis of breast cancer patients.

PMID- 12185335
TI  - The role of contrast-enhanced MR mammography for determining candidates for
      breast conservation surgery.
AB  - PURPOSE: The aim of this study was to assess the impact of preoperative magnetic
      resonance mammography (MRM) on the surgical determination of breast conservation
      treatment for breast cancer patients. METHODS: From September 1997 to March 2000,
      57 consecutive breast conservation treatment candidates were prospectively
      evaluated with conventional imaging studies (mammography and ultrasonography) and
      preoperative MRM. RESULTS: In 47 of 54 (87% ) breast cancer patients breast
      conservation surgery (BCS) was indicated on the basis of mammography (MMG) and
      ultrasonography (US). However in 40 of the 54 (74% ) patients BCS was indicated
      on the basis of MRM. Thirty-eight of the 40 patients ultimately underwent BCS and
      only 1 showed a positive margin. There were 7 patients whose MRM findings
      suggested that more aggressive treatment than BCS was needed but for whom US/MMG
      suggested that BCS was appropriate. Five of the 7 patients underwent mastectomy
      rather than BCS based on the MRM findings, which were justified by post-surgical
      histological findings. Of the 2 remaining patients who underwent BCS, one had a
      positive histological margin and one had recurrence, both of which resulted in
      salvage mastectomy. CONCLUSION: Our study suggests that high resolution
      preoperative MRM provides more accurate information compared with US and MMG for
      selecting candidates for BCS. Using MRM as a routine staging tool may reduce
      unnecessary repeated excisions. A larger study will be required to confirm these
      findings and to define the patients most likely to benefit from breast MR
      imaging.

PMID- 12185336
TI  - Utility of technetium-99m methoxyisobutyl isonitrile uptake analysis for
      prediction of the response to chemotherapy in advanced and relapsed breast
      cancer.
AB  - BACKGROUND: Technetium-99m methoxyisobutyl isonitrile (Tc-SESTAMIBI) is a
      substrate of P-glycoprotein and multidrug-resistance associated protein in drug
      resistant cells. To assess the clinical effectiveness of Tc-SESTAMIBI for
      predicting the chemotherapy response to treatment with anthracyclines and vinca
      alkaloids, we retrospectively evaluated the relationship between the accumulation
      of Tc-SESTAMIBI and the tumor response. METHODS: Thirteen patients, including 12
      advanced cases and 1 relapsed case, were investigated, all of whom had been
      treated with anthracyclines or a vinca alkaloid regimen. The accumulation of Tc
      SESTAMIBI was compared at 10 min and 2 h after Tc-SESTAMIBI administration. The
      relationship between the accumulation of Tc-SESTAMIBI and the tumor response
      following treatment with anthracyclines and vinca alkaloids was assessed.
      RESULTS: Eight of 13 patients responded to treatment with anthracyclines and
      vinca alkaloids, whereas 5 patients did not respond to treatment. At 10 min, 6
      (75.0% ) of the 8 responding patients had a high accumulation of Tc-SESTAMIBI,
      whereas 4 (80.0% ) of the 5 non-responding patients had a low accumulation of Tc
      SESTAMIBI. The overall predictive value was 76.9%. The relationship was not
      statistically significant (Fisher's test). The difference in the decrease of
      accumulation of Tc-SESTAMIBI between 10 min and 2 h was not associated with tumor
      response to treatment in 6 of the responding patients with high accumulation. Two
      false negative cases and one false positive case were observed, suggesting the
      presence of another factor contributing to drug sensitivity in tumor response,
      such as apoptosis-related genes. CONCLUSIONS: Assessment of the initial
      accumulation of Tc-SESTAMIBI can be a predictive marker of tumor response to
      treatment with anthracyclines and vinca alkaloids in patients with advanced and
      relapsed breast cancer. Further studies are required to explore other factors
      involved in the tumor response to treatment with anthracyclines and vinca
      alkaloids.

PMID- 12185338
TI  - Adenoma of the nipple in an adolescent.
AB  - We recently treated a 14-year-old girl with a clinically and histologically
      diagnosed with adenoma of the nipple. Enucleation of a mass preserving the nipple
      was successfully performed. Adenoma of the nipple is a rare disease which is
      often mistaken clinically for Paget's disease. About 200 cases of the tumors have
      been reported worldwide so far. The most common symptom is erosion of the nipple
      and nipple discharge. Our case had erosion of the nipple but no discharge.
      Adenoma of the nipple is a benign lesion which can be successfully treated by a
      simple surgery.

PMID- 12185337
TI  - Long-term results of breast conserving surgery for stages I and II breast cancer:
      experiences at Osaka Medical Center for Cancer and Cardiovascular Diseases.
AB  - PURPOSE: The purpose of this study is to summarize the long-term results of
      breast conserving surgery (BCS) for Japanese patients with stage I and II breast
      cancer at a single institute and to identify risk factors for local recurrence
      after BCS. PATIENTS AND METHODS: Between October 1986 and June 2000, 979 women
      underwent BCS with or without radiation therapy (RT). Overall survival, disease
      free survival and local recurrence rates were calculated by the Kaplan-Meier
      method. Risk factors for local recurrence were examined by multivariate analysis
      using the Cox proportional regression model. RESULTS: The 10-year overall
      survival rates were 90.9% for the surgery and radiation therapy (RT group) and
      89.3% for the surgery only group with a median follow-up time of 46 months. The
      10-year disease free survival rates were 85.1% in the RT group and 69.2% in the
      surgery only group (p=0.0001). The positive margin rate was 14.1% (138/979). The
      10-year overall survival rate of the patients with positive margins was 87.9%,
      compared with 90.8% for patients with negative margins (N.S.). The cumulative
      incidence of local recurrence at 10 years was significantly lower in the RT group
      (7.2% ) than in the surgery only group (27.5% ) (p<0.0001). Multivariate analysis
      showed that positive margins and lack of post-operative irradiation or adjuvant
      endocrine therapy were risk factors for non-inflammatory local recurrence.
      CONCLUSIONS: Our study indicates that BCS can be performed for Japanese women
      with early breast cancer. The margin status and post-operative irradiation had no
      influence on overall survival while but were significantly related to local
      recurrence.

PMID- 12185339
TI  - A case of neurilemmoma of the breast.
AB  - Neurilemmoma of the breast is rarely seen, although it is common at intracranial
      or peripheral sites. There have been only 14 cases described in the literature.
      We present the fifteenth case of a 64-year-old woman with neurilemmoma of the
      breast, the first to be diagnosed by fine needle aspiration cytology.
      Fibroadenoma must be distinguished from this tumor. Complete removal is the
      treatment of choice, considering the possibility of local recurrence and
      malignant change.

PMID- 12185340
TI  - Nodular mucinosis of the breast: a case report with clinical and imaging
      findings.
AB  - We present a very rare case of nodular mucinosis of the breast. A 30-year-old
      woman noticed a right breast lump and consulted at our hospital because it
      gradually increased in size. On physical examination, the lump was 30 x 25 mm in
      size, and was located in the upper outer quadrant close to the nipple of the
      right breast. It was well-demarcated, mobile and hard. Ultrasonography (US)
      showed a clearly circumscribed, lobulated, and homogeneous hypoechoic lesion.
      Mammography (MMG) showed a round-lobular-shaped radiopaque mass without
      microcalcifications or spicula formation. Fine needle aspiration cytology (FNA)
      revealed no malignancy and mucin. Histologically, the excised tumor consisted of
      an abundant myxoid substance with scattered spindle cells without epithelial
      elements in the mucous lake. The mucinous substance stained positively with
      Alcian blue. Nodular mucinosis, simulating mucinous carcinoma or phyllodes tumor
      on clinical and imaging examinations, should be included in the differential
      diagnosis in cases of mucinous lesions occurring near the nipple in a young
      woman.

PMID- 12185341
TI  - A case of granulomatous mastitis mimicking breast carcinoma.
AB  - A 58-year-old woman presenting with idiopathic granulomatous mastitis mimicking
      breast carcinoma is described. The mass was elastic, hard and painless, and
      located in the upper outer quadrant of the right breast. Fine needle aspiration
      cytology did not provide any diagnostic information. Mammography, ultrasonography
      and magnetic resonance imaging (MRI) strongly suggested malignancy. Excisional
      biopsy was performed for definitive diagnosis, and idiopathic granulomatous
      mastitis was demonstrated histopathologically. Neither wound complication nor
      recurrence has been identified in the patient, although corticosteroids were not
      used post operatively. We reviewed the literature, and found that our present
      case is rare in older patients, and that mammography, ultrasonography and MRI
      provide little information for differentiating between granulomatous mastitis and
      carcinoma.

PMID- 12185342
TI  - A next step in naming and classification of eye movement disorders and
      strabismus.

PMID- 12185343
TI  - A brief history of Strabismus in Latin America.

PMID- 12185344
TI  - Outcome of lamellar keratoplasty for limbal dermoids in children.
AB  - PURPOSE: We report on the surgical management, complications, postoperative
      visual acuity, and astigmatism of limbal dermoids in children. METHODS: This was
      a retrospective study of 49 children (51 eyes) treated between 1990 and 2000.
      Demographic data, age at surgery, details of the surgical procedure, the
      preoperative and postoperative visual acuity and astigmatism, the complications
      of surgery, and the ocular and systemic associations were recorded. Age at
      surgery was regressed against the size of the corneal graft, the visual outcome,
      and astigmatism. The size of the corneal graft was regressed against the visual
      outcome and astigmatism. A test for a difference in proportions of the
      preoperative and postoperative astigmatism was conducted. Postoperatively
      children were followed up until suture removal if necessary at 4 weeks. Children
      living locally continued follow-up at The Hospital for Sick Children, Toronto,
      Ontario, Canada; the rest were referred to their referring ophthalmologist.
      RESULTS: The mean age of the patients at surgery was 4.4 +/- 3.8 years (range, 1
      month to 15 years). Excision of the dermoid and lamellar keratoplasty was
      performed in 48 eyes, simple excision was performed in 2 eyes, and a penetrating
      graft was performed in 1 eye. The mean graft size (6.6 +/- 1.2 mm; range, 3.5-10
      mm) was inversely related to the age of the patient (P =.04). Three eyes had
      microperforations during excision of the dermoid. Opacification of part of the
      graft was seen in 10.2% of eyes (5/49) with a mild haze in 3 eyes.
      Postoperatively 96.7% of eyes (29/30) had a visual acuity greater than or equal
      to 6/24, with 86.7% (26/30) greater than or equal to 6/12; one eye had a visual
      acuity of 6/120. The size of the graft correlated inversely with the visual
      acuity (P =.03). Preoperative and postoperative refraction was recorded in 23
      patients. Astigmatism greater than 1 D was present in 43.4% preoperatively and in
      60% postoperatively (P =.6). There was no association between age at surgery (P
      =.6) and the size of the graft (P =.2) and the presence of postoperative
      astigmatism. CONCLUSION: Excellent visual results were achieved in the majority
      of patients. Younger children were operated on for visual reasons with larger
      grafts and a tendency for a lower visual acuity. Although astigmatism was noted
      to decrease in a few children after excision, a significant number had an
      increase in astigmatism postoperatively, which warrants a close follow-up in
      children operated during the amblyogenic age.

PMID- 12185345
TI  - Marginal myotomy of the minimally overacting inferior oblique muscle in
      asymmetric bilateral superior oblique palsies.
AB  - PURPOSE: We report the surgical results of marginal myotomy of a minimally
      overacting inferior oblique muscle in conjunction with traditional recession or
      myectomy of the greater overacting inferior oblique muscle in 10 patients with
      asymmetric bilateral superior oblique palsies and asymmetric inferior oblique
      overaction. METHODS: Ten consecutive patients with bilateral superior oblique
      palsies had a hypertropia in primary position (5-28 PD) and unequal inferior
      oblique overaction (0 to +2 in the lesser overacting inferior oblique muscle, +2
      to +4 in the greater overacting inferior oblique muscle). Reversal of the
      hypertropia was noted in ipsilateral oblique upgaze. All patients underwent a
      recession or myectomy of the greater overacting inferior oblique muscle and a
      marginal myotomy of the lesser overacting inferior oblique muscle. RESULTS: Seven
      patients had no vertical deviation in primary position, 2 patients had a residual
      hypertropia of 2 to 3 PD, and 1 patient had a residual hypertropia of 8 PD. The
      abnormal head position present preoperatively in 8 patients was eliminated or
      greatly improved after surgery. Postoperatively all but 1 inferior oblique
      overaction was graded as 0 to trace. Mean follow-up time was 19 months (range,
      1.5-68 months). CONCLUSIONS: In bilateral superior oblique palsies with
      asymmetric inferior oblique overaction, a mildly overacting inferior oblique
      muscle can be corrected by marginal myotomy, combined with a recession or
      myectomy of the greater overacting inferior oblique muscle. This procedure can
      reduce or eliminate the hypertropia in primary position while minimizing the
      possibility of residual inferior oblique overaction.

PMID- 12185346
TI  - Retinal hemorrhages in meningococcal septicemia.
AB  - PURPOSE: Meningococcal septicemia is associated with coagulopathy and hemorrhagic
      tendency. We carried out this study to determine the incidence of retinal
      hemorrhages in meningococcal septicemia. METHODS: This was a prospective study
      involving all children admitted to the Sheffield Children's Hospital, Sheffield,
      England, with a diagnosis of meningococcal septicemia. Confirmation of
      meningococcal infection was by blood culture or DNA analysis using polymerase
      chain reaction. The children underwent ocular examination including dilated
      fundus examination by direct and indirect ophthalmoscopy. Details of their
      coagulation status were also obtained. RESULTS: Twelve children (mean age, 4.5
      years) with a confirmed diagnosis of meningococcal septicemia were included. All
      children had coagulopathy. Retinal hemorrhages were found in 5 children (42%).
      The disease was fatal in 3 children. Group C meningococcus was responsible for
      the infection in all those with retinal hemorrhages and those with fatal outcome.
      CONCLUSIONS: Retinal hemorrhage is a common feature in meningococcal septicemia.
      Ophthalmic evaluation should be part of the assessment of children with
      meningococcal septicemia. Future studies on meningococcal disease should include
      retinal hemorrhage as another parameter in the assessment. This should help us to
      understand the role of retinal hemorrhage in the prognosis of this serious
      disease.

PMID- 12185347
TI  - Investigation of hemodynamic changes after strabismus surgery using color Doppler
      imaging.
AB  - PURPOSE: To investigate hemodynamic changes after strabismus surgery using color
      Doppler imaging (CDI). METHOD: Group 1 patients (n = 13) underwent surgery on a
      single horizontal rectus muscle, and group 2 (n = 13) underwent surgery on both
      horizontal rectus muscles. Subjects with no systemic or ophthalmologic disorders
      were selected as controls (n = 16). In group 1 and group 2, CDI of the ophthalmic
      artery (OA), the central retinal artery (CRA), and the nasal and temporal
      posterior ciliary arteries (PCAs) was performed before surgical correction and on
      postoperative days 1 and 7. For each vessel, peak systolic (V(max)), end
      diastolic (V(min)), and mean (V(mean)) blood flow velocities were measured, in
      addition to the resistivity index (RI) and pulsatility index (PI). RESULTS:
      V(max) in the OA on postoperative day 1 was higher in group 2 than in group 1 (P
      =.004). V(min) in the OA on postoperative day 1 was significantly higher in group
      2 than in the controls (P =.001) and group 1 (P =.001). For group 2, comparison
      of the OA preoperative findings to the findings on postoperative day 1 showed
      that V(min) (P =.003) and V(mean) (P =.02) increased significantly, and the RI (P
      =.01) and PI (P =.006) decreased significantly. These significant differences
      were not observed on day 7 (P >.05). CONCLUSION: Surgery on both horizontal
      rectus muscles in an eye causes hemodynamic changes in the OA in the early
      postoperative period.

PMID- 12185348
TI  - Case series of 12 children with progressive axial myopia following unilateral
      cataract extraction.
AB  - PURPOSE: We report the occurrence of unilateral progressive axial myopia
      ipsilaterally in a retrospective analysis of 12 children following uniocular
      cataract surgery. METHODS: A retrospective analysis of the case records of
      children who had developed progressive ipsilateral axial myopia following
      unilateral cataract surgery was done. Follow-up ranged from 4 years to 14 years.
      RESULTS: Twelve children, 7 male and 5 female, were eligible for the study. Mean
      age at the time of cataract surgery was 6.7 +/- 2.5 years (range, 4-11 years) and
      follow-up period was 7.8 +/- 3.1 years (range, 4-14 years). Ten children (83.3%)
      had traumatic cataracts of which 8 had undergone repair of penetrating eye
      injuries and 2 had suffered blunt trauma. Two patients (16.7%)had been operated
      for unilateral developmental cataracts. Three children had aphakia and nine had
      pseudophakia. Degree of myopic shift ranged from -4.75 D to -15 D (mean, -7.35 +/
      3.51 D). Axial length difference between the 2 eyes ranged from 1 mm to 3.5 mm
      (mean, 2.2 +/- 0.9 mm). Mean increase of axial length from preoperative recording
      to final follow-up was 2.53 +/- 0.90 mm (range, 1.6-4 mm). Three children had to
      undergo IOL explantation and 1 had posterior chamber intraocular lens exchange
      due to high unilateral myopia. The rest were visually rehabilitated with either
      spectacles or contact lenses. CONCLUSION: Following cataract surgery pediatric
      eyes may suffer from progressive axial myopia. Trauma or multiple ocular
      surgeries may be predisposing factors.

PMID- 12185349
TI  - Postoperative stereoacuity following realignment for chronic acquired strabismus
      in adults.
AB  - BACKGROUND: There is controversy regarding whether or not visually mature
      individuals can permanently lose stereoacuity and under what conditions
      stereoacuity can be regained. Some have proposed a critical duration of
      misalignment in adults beyond which recovery of fine stereoacuity is not
      possible, despite successful surgical alignment. METHODS: Twenty-one adult
      patients (median age 59 years) with large-angle acquired strabismus and who were
      successfully surgically aligned after 7 to 501 months of misalignment were
      studied. Subjects had no evidence of motor or sensory fusion since the onset of
      strabismus, on preoperative exam, or by history. Stereoacuity was measured using
      1 or more of the Frisby, Preschool Randot and Titmus tests, at 8 weeks and at 12
      months. Data from tests with monocular clues were not used. RESULTS: At total of
      67% of patients with chronic acquired strabismus and no preoperative fusion
      regained measurable stereoacuity and 44% regained fine stereoacuity of at least
      60 seconds of arc. Of 10 patients with no or subnormal stereoacuity 8 weeks
      postoperatively, 6 (60%) showed improvement at the 12-month visit. Misalignment
      for up to 4 years did not preclude the development of postoperative stereoacuity.
      CONCLUSIONS: Although a minority of adult strabismus patients may permanently
      lose stereoacuity despite successful alignment for acquired strabismus, the
      majority do show recovery. Such recovery of stereoacuity may take several months
      to occur. In our adult series, duration of misalignment did not predict failure
      to recover stereoacuity.

PMID- 12185350
TI  - Clinical assessment of conjunctival and episcleral vessel tortuosity in juvenile
      dermatomyositis.
AB  - PURPOSE: Conjunctival and episcleral vessel tortuosity are thought to be
      associated features of juvenile dermatomyositis. This study was conducted to
      determine the interobserver reliability of assessing normal and abnormal
      conjunctival and episcleral vessels from photographs of patients with and without
      juvenile dermatomyositis. METHODS: Color and red-free external ocular photographs
      of each eye of 28 children were assessed by 5 pediatric ophthalmologists from The
      Hospital for Sick Children. Fifteen of these pairs of photographs were of normal
      control eyes and 13 were from eyes of patients with juvenile dermatomyositis. On
      a standardized form each ophthalmologist was asked to determine whether both the
      conjunctival and episcleral vessels appeared normal or abnormal. Interobserver
      agreement was calculated by the weighted kappa statistic. The sensitivity and
      specificity of abnormal vessels for diagnosing juvenile dermatomyositis were also
      determined. RESULTS: Interobserver agreement for assessing conjunctival and
      episcleral vessels was 0.18 and -0.005, respectively. The average sensitivity and
      specificity of the evaluators for correctly assessing conjunctival vessels were
      0.70 and 0.70, and for episcleral vessels, 0.67 and 0.47, respectively.
      CONCLUSIONS: There was low interobserver agreement in distinguishing between
      normal and abnormal eyes based on conjunctival and episcleral vessels. The
      sensitivity and specificity for identifying patients with juvenile
      dermatomyositis based on the appearance of vessels alone were relatively low. The
      appearance of conjunctival and episcleral vessels should be assessed in the
      context of other ocular and periocular findings of patients with juvenile
      dermatomyositis.

PMID- 12185351
TI  - The immediate postoperative adjustment of sutures in strabismus surgery with
      comaintenance of anesthesia using propofol and midazolam.
AB  - PURPOSE: Adjustable suture techniques are used to reduce the reoperation rate in
      strabismus surgery, but traditionally require that final adjustments be made
      between 1 to 24 hours after surgery. The purpose of this study was to evaluate a
      new anesthetic technique that would allow immediate postoperative adjustment of
      sutures in strabismus surgery, thereby improving patient convenience and comfort.
      METHODS: This was a prospective study of strabismus patients who were judged to
      be appropriate candidates for adjustable sutures. Comaintenance of anesthesia was
      accomplished using a stepped-down infusion of propofol with midazolam. Final
      suture adjustments were performed in the operating room immediately upon
      completion of strabismus surgery. Patient satisfaction was assessed 24 hours
      later. Patients were followed for 6 weeks postoperatively. RESULTS: A total of 16
      patients were studied, with 8 patients having horizontal muscle surgery, 7
      patients with vertical muscle surgery, and 1 patient undergoing both horizontal
      and vertical muscle surgery. The change in deviation after 6 weeks of follow-up
      was 8 PD or less horizontally in all patients and 4 PD or less vertically in 87%
      of patients when compared with the alignment in the operating room. Diplopia, if
      present, resolved in 85% of patients. One patient (6.7%) required a second
      surgery. The mean drift at 2 weeks horizontally was 1.87 PD esotropic (range, -6
      PD exophoric to 18 PD esotropic) and vertically 0.94 PD (range, -4 PD hypotropic
      to 4 PD hypertropic). The mean drift at 6 weeks horizontally was -0.27 PD
      exotropic (range, -8 PD exophoric to 8 PD esotropic) and vertically 0.6 PD
      (range, -6 PD hypotropic to 10 PD hypertropic). CONCLUSION: The immediate
      postoperative adjustment of sutures in strabismus surgery may be accurately
      performed using this new anesthetic technique.

PMID- 12185352
TI  - Preschool Worth 4-Shape test: testability, reliability, and validity.
AB  - PURPOSE: The Worth 4-Dot is used to assess binocular fusion, but it is difficult
      to use with young children. We modified the Worth 4-Dot by replacing the circles
      with shapes while maintaining the same color configuration. The purpose of this
      study was to determine the testability, reliability, and validity of the Worth 4
      Shape test. METHODS: Subjects aged 2 to 8 years and 4 patients aged over 8 years
      with best-corrected visual acuity of 20/40 or greater (n = 131 patients, n = 123
      normals) attempted test and retest at 35 cm and 3m using the Worth 4-Shape and
      Worth 4-Dot. To provide a gold standard, medical history, bifoveal fixation, and
      stereoacuity were reviewed. RESULTS: Testability of the Worth 4-Shape was
      significantly higher than the Worth 4-Dot both in children aged less than 4 years
      (95.9% vs 79.5% at 35 cm, P <.001; 79.5% vs 55.1% at 3 m, P <.001) and older than
      4 years (98.5% vs 88.6% at 35 cm, P <.001; 90.9% vs 82.4% at 3m, P =.04). Test
      retest analysis found comparable concordance for the Worth 4-Shape and Worth 4
      Dot tests (P >.3). The sensitivity and specificity of the Worth 4-Shape (92%,
      97%) and Worth 4-Dot (90%, 94%) were comparable. Between-test analysis found 96%
      agreement between both tests at 35 cm and 97% agreement at 3m. CONCLUSIONS: The
      success rate for the Worth 4-Shape is higher than the Worth 4-Dot, especially in
      children aged less than 4 years, and has equivalent accuracy. The Worth 4-Shape
      test-retest reliability is high supporting its validity for use with young
      children.

PMID- 12185353
TI  - Hyperbaric oxygen therapy in the treatment of orbital gas gangrene.
AB  - Clostridial gas gangrene (myonecrosis) is a rapidly progressive, life-threatening
      infection. The occurrence of clostridial gas gangrene in the orbit is uncommon.
      We present a case of gas gangrene in the orbit of a child, with Clostridium
      perfringens isolated from the wound. Our patient was successfully treated with
      extensive surgical debridement, anti-microbial therapy, and hyperbaric oxygen
      therapy. Hyperbaric oxygen is established as an adjuvant therapy of clostridial
      gas gangrene and has been shown to significantly reduce morbidity and mortality.
      To our knowledge, this is the first reported case of using hyperbaric oxygen
      therapy in the treatment of orbital gas gangrene.

PMID- 12185354
TI  - Recurrence of iris stromal cyst following aspiration and resection.
AB  - We describe a 3-month-old patient with a primary epithelial cyst of the iris
      stroma. Although these cysts account for 16% of all childhood iris cysts, these
      cysts are uncommon with only a small number of reported cases.(1-6) Because our
      patient's cyst had amblyogenic potential, we proceeded with surgical treatment.
      The cyst was aspirated, but it recurred within 7 weeks. Sector iridectomy with
      excision of the cyst was performed, again with recurrence and subsequent glaucoma
      and cataract. These cysts present difficult management issues concerning the
      choice of initial surgical treatment and subsequent complications.

PMID- 12185355
TI  - Spontaneous medial rectus hemorrhage in a patient with acute myelogenous
      leukemia.

PMID- 12185356
TI  - Giant retinal tear and meningococcus endogenous endophthalmitis.
AB  - Giant retinal tear is seen in association with Stickler's syndrome, Marfan
      syndrome, homocystinurea and after ocular trauma. Although bacterial
      meningitis(1) is not common since the advent of various antibiotics,
      meningococcus is the second most common cause of bacterial meningitis. Endogenous
      endophthalmitis(2) remains a challenge to clinicians despite the success of
      antibiotics in reducing its frequency and severity. The association of giant
      retinal tear and meningococcal endogenous endophthalmitis is not yet reported in
      the literature. We report here on a 14-year-old girl who developed a giant
      retinal tear after meningococcal meningitis and endogenous endophthalmitis, and
      we discuss the possible factors of its cause.

PMID- 12185357
TI  - Pediatric alacrima, achalasia, and mental retardation.
AB  - Absence or deficiency of tear volume (alacrima) is rarely seen in pediatric
      ophthalmology. It is often a part of the multiple systemic anomalies like Riley
      Day syndrome and anhidrotic ectodermal dysplasia, or it may be associated with
      adrenal gland insufficiency, achalasia, and neurologic disorders like Allgrove's
      syndrome. We report on a 7-year-old girl presenting alacrima, achalasia, and
      mental retardation with normal adrenocortical function.

PMID- 12185358
TI  - Central retinal artery occlusion and disc edema in a child.
AB  - Obstruction of the retinal arterial system is most commonly associated with
      elderly patient populations. The major etiologic factor in adults has been
      attributed to emboli from atherosclerotic vascular disease of the carotid
      arteries, with about 75% of patients over the age of 40 years demonstrating this
      finding. Conversely, arterial obstruction in young patients is rarely secondary
      to atheromatous disease and has a variety of causative factors.(1) We describe an
      unusual case of a previously healthy 8-year-old boy who developed a unilateral
      central retinal artery occlusion in conjunction with marked optic disc edema. The
      etiology of these pathologic lesions was attributed to a viral-like syndrome.
      Vision rapidly deteriorated to no light perception and remained unchanged despite
      treatment.

PMID- 12185359
TI  - Rectus, recti, rectii, wrecked?

PMID- 12185360
TI  - Binocular function in patients with refractive monovision.

PMID- 12185362
TI  - Activation of Notch-1 signaling maintains the neoplastic phenotype in human Ras
      transformed cells.
AB  - Truncated Notch receptors have transforming activity in vitro and in vivo.
      However, the role of wild-type Notch signaling in neoplastic transformation
      remains unclear. Ras signaling is deregulated in a large fraction of human
      malignancies and is a major target for the development of novel cancer
      treatments. We show that oncogenic Ras activates Notch signaling and that wild
      type Notch-1 is necessary to maintain the neoplastic phenotype in Ras-transformed
      human cells in vitro and in vivo. Oncogenic Ras increases levels and activity of
      the intracellular form of wild-type Notch-1, and upregulates Notch ligand Delta-1
      and also presenilin-1, a protein involved in Notch processing, through a p38
      mediated pathway. These observations place Notch signaling among key downstream
      effectors of oncogenic Ras and suggest that it might be a novel therapeutic
      target.

PMID- 12185361
TI  - Parathyroid hormone-related peptide is a naturally occurring, protein kinase A
      dependent angiogenesis inhibitor.
AB  - Angiogenesis is a highly regulated process that results from the sequential
      actions of naturally occurring stimulators and inhibitors. Here, we show that
      parathyroid hormone-related peptide, a peptide hormone derived from normal and
      tumor cells that regulates bone metabolism and vascular tone, is a naturally
      occurring angiogenesis inhibitor. Parathyroid hormone-related peptide or a ten
      amino-acid peptide from its N terminus inhibits endothelial cell migration in
      vitro and angiogenesis in vivo by activating endothelial cell protein kinase A.
      Activation of protein kinase A inhibits cell migration and angiogenesis by
      inhibiting the small GTPase Rac. In contrast, inhibition of protein kinase A
      reverses the anti-migratory and anti-angiogenic properties of parathyroid hormone
      related peptide. These studies show that parathyroid hormone-related peptide is a
      naturally occurring angiogenesis inhibitor that functions by activation of
      protein kinase A.

PMID- 12185363
TI  - Enzymatically labeled chromosomal probes for in situ identification of human
      cells in xenogeneic transplant models.
AB  - Analysis of the viability, differentiation, clonogenicity and function of human
      stem/progenitor cells requires suitable xenograft models. However, the
      identification of transplanted cells has been generally difficult. Fluorescence
      in situ hybridization is a tedious method for analyzing tissues, and localization
      of transplanted cells with X or Y chromosome probes is limited by the sparse
      signals produced. Therefore, we examined the possibility of generating either pan
      nuclear signals with a total human DNA probe or multiple nuclear signals with a
      pan-centromeric human DNA probe. The probes were labeled with digoxigenin to make
      reaction products visible by light microscopy and to allow the use of
      immunohistochemistry methods incorporating various color schemes to demonstrate
      specific properties of transplanted cells. The ability to localize all types of
      nucleated human cells with such probes will facilitate studies of stem cell
      biology and cell and gene therapy, as well as the development of new animal
      models.

PMID- 12185364
TI  - Mutant deoxynucleotide carrier is associated with congenital microcephaly.
AB  - The disorder Amish microcephaly (MCPHA) is characterized by severe congenital
      microcephaly, elevated levels of alpha-ketoglutarate in the urine and premature
      death. The disorder is inherited in an autosomal recessive pattern and has been
      observed only in Old Order Amish families whose ancestors lived in Lancaster
      County, Pennsylvania. Here we show, by using a genealogy database and automated
      pedigree software, that 23 nuclear families affected with MCPHA are connected to
      a single ancestral couple. Through a whole-genome scan, fine mapping and
      haplotype analysis, we localized the gene affected in MCPHA to a region of 3 cM,
      or 2 Mb, on chromosome 17q25. We constructed a map of contiguous genomic clones
      spanning this region. One of the genes in this region, SLC25A19, which encodes a
      nuclear mitochondrial deoxynucleotide carrier (DNC), contains a substitution that
      segregates with the disease in affected individuals and alters an amino acid that
      is highly conserved in similar proteins. Functional analysis shows that the
      mutant DNC protein lacks the normal transport activity, implying that failed
      deoxynucleotide transport across the inner mitochondrial membrane causes MCPHA.
      Our data indicate that mitochondrial deoxynucleotide transport may be essential
      for prenatal brain growth.

PMID- 12185365
TI  - New genes involved in cancer identified by retroviral tagging.
AB  - Retroviral insertional mutagenesis in BXH2 and AKXD mice induces a high incidence
      of myeloid leukemia and B- and T-cell lymphoma, respectively. The retroviral
      integration sites (RISs) in these tumors thus provide powerful genetic tags for
      the discovery of genes involved in cancer. Here we report the first large-scale
      use of retroviral tagging for cancer gene discovery in the post-genome era. Using
      high throughput inverse PCR, we cloned and analyzed the sequences of 884 RISs
      from a tumor panel composed primarily of B-cell lymphomas. We then compared these
      sequences, and another 415 RIS sequences previously cloned from BXH2 myeloid
      leukemias and from a few AKXD lymphomas, against the recently assembled mouse
      genome sequence. These studies identified 152 loci that are targets of retroviral
      integration in more than one tumor (common retroviral integration sites, CISs)
      and therefore likely to encode a cancer gene. Thirty-six CISs encode genes that
      are known or predicted to be genes involved in human cancer or their homologs,
      whereas others encode candidate genes that have not yet been examined for a role
      in human cancer. Our studies demonstrate the power of retroviral tagging for
      cancer gene discovery in the post-genome era and indicate a largely unrecognized
      complexity in mouse and presumably human cancer.

PMID- 12185368
TI  - The role of the transcriptional regulator Ptf1a in converting intestinal to
      pancreatic progenitors.
AB  - Pancreas development begins with the formation of buds at specific sites in the
      embryonic foregut endoderm. We used recombination-based lineage tracing in vivo
      to show that Ptf1a (also known as PTF1-p48) is expressed at these early stages in
      the progenitors of pancreatic ducts, exocrine and endocrine cells, rather than
      being an exocrine-specific gene as previously described. Moreover, inactivation
      of Ptf1a switches the character of pancreatic progenitors such that their progeny
      proliferate in and adopt the normal fates of duodenal epithelium, including its
      stem-cell compartment. Consistent with the proposal that Ptf1a supports the
      specification of precursors of all three pancreatic cell types, transgene-based
      expression of Pdx1, a gene essential to pancreas formation, from Ptf1a cis
      regulatory sequences restores pancreas tissue to Pdx1-null mice that otherwise
      lack mature exocrine and endocrine cells because of an early arrest in
      organogenesis. These experiments provide evidence that Ptf1a expression is
      specifically connected to the acquisition of pancreatic fate by undifferentiated
      foregut endoderm.

PMID- 12185369
TI  - A troubling story: insurance and medical research in Saskatchewan.

PMID- 12185366
TI  - High-throughput retroviral tagging to identify components of specific signaling
      pathways in cancer.
AB  - Genetic screens carried out in lower organisms such as yeast, Drosophila
      melanogaster and Caenorhabditis elegans have revealed many signaling pathways.
      For example, components of the RAS signaling cascade were identified using a
      mutant eye phenotype in D. melanogaster as a readout. Screening is usually based
      on enhancing or suppressing a phenotype by way of a known mutation in a
      particular signaling pathway. Such in vivo screens have been difficult to carry
      out in mammals, however, owing to their relatively long generation times and the
      limited number of animals that can be screened. Here we describe an in vivo
      mammalian genetic screen used to identify components of pathways contributing to
      oncogenic transformation. We applied retroviral insertional mutagenesis in Myc
      transgenic (E mu Myc) mice lacking expression of Pim1 and Pim2 to search for
      genes that can substitute for Pim1 and Pim2 in lymphomagenesis. We determined the
      chromosomal positions of 477 retroviral insertion sites (RISs) derived from 38
      tumors from E mu Myc Pim1(-/-) Pim2(-/-) mice and 27 tumors from E mu Myc control
      mice using the Ensembl and Celera annotated mouse genome databases. There were 52
      sites occupied by proviruses in more than one tumor. These common insertion sites
      (CISs) are likely to contain genes contributing to tumorigenesis. Comparison of
      the RISs in tumors of Pim-null mice with the RISs in tumors of E mu Myc control
      mice indicated that 10 of the 52 CISs belong to the Pim complementation group. In
      addition, we found that Pim3 is selectively activated in Pim-null tumor cells,
      which supports the validity of our approach.

PMID- 12185370
TI  - Differential predictors of pain and disability in patients with whiplash
      injuries.
AB  - The psychological predictors of pain and disability were examined in a sample of
      people who sustained whiplash injuries during rear-end motor vehicle accidents.
      Sixty-five patients referred to a specialty pain clinic with a diagnosis of
      whiplash injury completed measures of depression, anxiety, catastrophizing, pain
      and perceived disability. Regression analysis revealed that psychological
      variables accounted for 18% of the variance in pain ratings. The magnification
      subscale of the Pain Catastrophizing Scale was the only variable that contributed
      significant, unique variance to the prediction of pain. Psychological variables
      accounted for 37% of the variance in perceived disability scores. In the latter
      analysis, however, none of the independent variables contributed significant,
      unique variance to the prediction of perceived disability. Psychological
      variables accounted for significant variance in disability ratings, even when
      controlling for pain intensity. Discussion focuses on the need to draw clearer
      distinctions between determinants of pain and disability, and directions for
      interventions aimed at minimizing disability following whiplash injury are
      suggested.

PMID- 12185371
TI  - Disrupted sleep patterns and daily functioning in patients with chronic pain.
AB  - OBJECTIVE: To investigate the role of disturbed sleep in the daily functioning of
      persons with chronic pain. subjects and METHODS: Participants comprised 287
      patients seeking treatment for chronic pain at a university pain clinic. All
      patients completed the measures employed in the present study as part of a
      comprehensive initial evaluation. RESULTS: Descriptive analyses showed that 88.9%
      of patients reported as least one problem with disturbed sleep. Correlation
      analyses showed that greater sleep disturbance was associated with greater pain,
      disability, depression and physical symptoms, and less daily uptime. Hierarchical
      regression analyses showed that sleep disturbance predicted disability, daily
      uptime and physical symptoms independent of pain or depression. CONCLUSIONS:
      Sleep disruption is usually considered to be a consequence of the pain
      experience. However, the results of the present study reinforce the view that
      sleep disturbance may have a bidirectional relation with other features of
      chronic pain. Future studies should confirm that repairing disrupted sleep leads
      to an improvement in patients' daily activity and a reduction in their suffering.

PMID- 12185367
TI  - Genome-wide retroviral insertional tagging of genes involved in cancer in Cdkn2a
      deficient mice.
AB  - We have used large-scale insertional mutagenesis to identify functional landmarks
      relevant to cancer in the recently completed mouse genome sequence. We infected
      Cdkn2a(-/-) mice with Moloney murine leukemia virus (MoMuLV) to screen for loci
      that can participate in tumorigenesis in collaboration with loss of the Cdkn2a
      encoded tumor suppressors p16INK4a and p19ARF. Insertional mutagenesis by the
      latent retrovirus was synergistic with loss of Cdkn2a expression, as indicated by
      a marked acceleration in the development of both myeloid and lymphoid tumors. We
      isolated 747 unique sequences flanking retroviral integration sites and mapped
      them against the mouse genome sequence databases from Celera and Ensembl. In
      addition to 17 insertions targeting gene loci known to be cancer-related, we
      identified a total of 37 new common insertion sites (CISs), of which 8 encode
      components of signaling pathways that are involved in cancer. The effectiveness
      of large-scale insertional mutagenesis in a sensitized genetic background is
      demonstrated by the preference for activation of MAP kinase signaling,
      collaborating with Cdkn2a loss in generating the lymphoid and myeloid tumors.
      Collectively, our results show that large-scale retroviral insertional
      mutagenesis in genetically predisposed mice is useful both as a system for
      identifying genes underlying cancer and as a genetic framework for the assignment
      of such genes to specific oncogenic pathways.

PMID- 12185372
TI  - Central hyperexcitability in chronic musculoskeletal pain: a conceptual
      breakthrough with multiple clinical implications.
AB  - Recent investigations of dysfunctional pain processing in the central nervous
      system have contributed much knowledge about the development of chronic
      musculoskeletal pain. Many common chronic musculoskeletal pain syndromes -
      including regional myofascial pain syndromes, whiplash pain syndromes, refractory
      work-related neck-shoulder pain, certain types of chronic low back pain,
      fibromyalgia and others - may essentially be explained by abnormalities in
      central pain modulation. The growing awareness of dysfunctional central pain
      modulation may be a conceptual breakthrough leading to a better understanding of
      common chronic pain disorders. A new paradigm will have multiple clinical
      implications, including re-evaluation of clinical practice routines and
      rehabilitation methods, and will focus on controversial issues of medicolegal
      concern. The concept of dysfunctional central pain processing will also
      necessitate a mechanism-based classification of pain for the selection of
      individual treatment and rehabilitation programs for subgroups of patients with
      chronic musculoskeletal pain due to different pathophysiological mechanisms.

PMID- 12185373
TI  - Cannabis for chronic pain: case series and implications for clinicians.
AB  - BACKGROUND: Chronic pain is one of the most common reasons for therapeutic
      cannabis use. OBJECTIVES: To describe therapeutic cannabis use among patients
      with chronic pain. METHODS: Patients with chronic pain who voluntarily indicated
      that they used cannabis therapeutically completed a questionnaire about the type
      of cannabis used, the mode of administration, the amount used and the frequency
      of use, and their perception of the effectiveness of cannabis on a set of pain
      associated symptoms and side effects. The study was approved by the McGill
      University Health Centre Research Ethics Board. RESULTS: Fifteen patients (10
      male) were interviewed (median age 49.5 years, range 24 to 68 years). All
      patients smoked herbal cannabis for therapeutic reasons (median duration of use
      six years, range two weeks to 37 years). Seven patients only smoked at night-time
      (median dose eight puffs, range two to eight puffs), and eight patients used
      cannabis mainly during the day (median dose three puffs, range two to eight
      puffs); the median frequency of use was four times per day (range one to 16 times
      per day). Twelve patients reported improvement in pain and mood, while 11
      reported improvement in sleep. Eight patients reported a 'high'; six denied a
      'high'. Tolerance to cannabis was not reported. CONCLUSIONS: The results of this
      self-selected case series must be interpreted with caution. Small doses of smoked
      cannabis may improve pain, mood and sleep in some patients with chronic pain.
      Clinical trials are warranted to test these effects. Further prospective studies
      should examine the patterns and prevalence of cannabis use among chronic pain
      populations.

PMID- 12185375
TI  - Pain: a culturally informed experience.

PMID- 12185374
TI  - Insurance research and medical ethics.

PMID- 12185376
TI  - A tobacco cDNA reveals two different transcription patterns in vegetative and
      reproductive organs.
AB  - In order to identify genes expressed in the pistil that may have a role in the
      reproduction process, we have established an expressed sequence tags project to
      randomly sequence clones from a Nicotiana tabacum stigma/style cDNA library. A
      cDNA clone (MTL-8) showing high sequence similarity to genes encoding glycine
      rich RNA-binding proteins was chosen for further characterization. Based on the
      extensive identity of MTL-8 to the RGP-1a sequence of N. sylvestris, a primer was
      defined to extend the 5' sequence of MTL-8 by RT-PCR from stigma/style RNAs. The
      amplification product was sequenced and it was confirmed that MTL-8 corresponds
      to an mRNA encoding a glycine-rich RNA-binding protein. Two transcripts of
      different sizes and expression patterns were identified when the MTL-8 cDNA
      insert was used as a probe in RNA blots. The largest is 1,100 nucleotides (nt)
      long and markedly predominant in ovaries. The smaller transcript, with 600 nt, is
      ubiquitous to the vegetative and reproductive organs analyzed (roots, stems,
      leaves, sepals, petals, stamens, stigmas/styles and ovaries). Plants submitted to
      stress (wounding, virus infection and ethylene treatment) presented an increased
      level of the 600-nt transcript in leaves, especially after tobacco necrosis virus
      infection. In contrast, the level of the 1,100-nt transcript seems to be
      unaffected by the stress conditions tested. Results of Southern blot experiments
      have suggested that MTL-8 is present in one or two copies in the tobacco genome.
      Our results suggest that the shorter transcript is related to stress while the
      larger one is a flower predominant and nonstress-inducible messenger.

PMID- 12185377
TI  - Genetic characterization of dengue virus type 3 isolates in the State of Rio de
      Janeiro, 2001.
AB  - The genetic characterization of dengue virus type 3 (DEN-3) strains isolated from
      autochthonous cases in the State of Rio de Janeiro, Brazil, in 2001 is presented.
      Restriction site-specific (RSS)-PCR performed on 22 strains classified the
      Brazilian DEN-3 viruses as subtype C, a subtype that contains viruses from Sri
      Lanka, India, Africa and recent isolates from Central America. Nucleic acid
      sequencing (positions 278 to 2550) of one DEN-3 strain confirmed the origin of
      these strains, since genotype III - classified by sequencing - and RSS-PCR
      subtype C are correlated. This genetic subtype has been associated with
      hemorrhagic dengue epidemics and the information provided here could be useful to
      implement appropriate prevention and control measures.

PMID- 12185378
TI  - Molecular identification of Sicilian (deltabeta) degrees-thalassemia associated
      with beta-thalassemia and hemoglobin S in Brazil.
AB  - We describe the clinical and molecular characteristics of two unrelated Brazilian
      families with an association of the Sicilian form of (deltabeta) degrees 
      thalassemia with hemoglobin S and beta-thalassemia. Direct sequencing of the beta
      globin gene showed only the hemoglobin S mutation in patient 1 and the beta
      thalassemia IVS1-110 in patient 2. The other allele was deleted in both patients
      and PCR of DNA samples of the breakpoint region of both patients showed a band of
      approximately 1,150 bp, expected to be observed in the DNA of carriers of
      Sicilian (deltabeta) degrees -thalassemia. The nucleotide sequence of this
      fragment confirmed the Sicilian deletion. There are few reports concerning the Hb
      S/(deltabeta) degrees -thalassemia association and patient 2 is the first
      reported case of Sicilian type of (deltabeta) degrees -thalassemia in association
      with beta-thalassemia documented at the molecular level.

PMID- 12185380
TI  - Bone mineral density in young women of the city of Sao Paulo, Brazil: correlation
      with both collagen type I alpha 1 gene polymorphism and clinical aspects.
AB  - Osteoporosis is a multifactorial disease with great impact on morbidity and
      mortality mainly in postmenopausal women. Although it is recognized that factors
      related to life-style and habits may influence bone mass formation leading to
      greater or lower bone mass, more than 85% of the variation in bone mineral
      density (BMD) is genetically determined. The collagen type I alpha 1 (COLIA1)
      gene is a possible risk factor for osteoporosis. We studied a population of 220
      young women from the city of Sao Paulo, Brazil, with respect to BMD and its
      correlation with both COLIA1 genotype and clinical aspects. The distribution of
      COLIA1 genotype SS, Ss and ss in the population studied was 73.6, 24.1 and 2.3%,
      respectively. No association between these genotypes and femoral or lumbar spine
      BMD was detected. There was a positive association between lumbar spine BMD and
      weight (P<0.0001), height (P<0.0156), and body mass index (BMI) (P<0.0156), and a
      negative association with age at menarche (P<0.0026). There was also a positive
      association between femoral BMD and weight (P<0.0001), height (P<0.0001), and BMI
      (P<0.0001), and a negative correlation with family history for osteoporosis
      (P<0.041). There was no association between the presence of allele s and reduced
      BMD. We conclude that a family history of osteoporosis and age at menarche are
      factors that may influence bone mass in our population.

PMID- 12185379
TI  - Improved glycemic control by acarbose therapy in hypertensive diabetic patients:
      effects on blood pressure and hormonal parameters.
AB  - A double-blind, randomized, placebo-controlled study was carried out on 44
      hypertensive type 2 diabetic subjects previously treated by diet associated or
      not with sulfonylurea to assess the effects of acarbose-induced glycemic control
      on blood pressure (BP) and hormonal parameters. Before randomization and after a
      22-week treatment period (100 to 300 mg/day), the subjects were submitted to a
      standard meal test and to 24-h ambulatory BP monitoring (ABPM) and had plasma
      glucose, glycosylated hemoglobin, lipid profile, insulin, proinsulin and leptin
      levels determined. Weight loss was found only in the acarbose-treated group (75.1
      +/- 11.6 to 73.1 +/- 11.6 kg, P<0.01). Glycosylated hemoglobin decreased only in
      the acarbose group (6.4 +/- 1.7 to 5.6 +/- 1.9%, P<0.05). Fasting proinsulin
      decreased only in the acarbose group (23.4 +/- 19.3 to 14.3 +/- 13.6 pmol/l,
      P<0.05), while leptin decreased in both (placebo group: 26.3 +/- 6.1 to 23.3 +/-
      9.4 and acarbose group: 25.0 +/- 5.5 to 22.7 +/- 7.9 ng/ml, P<0.05). When the
      subset of acarbose-treated patients who improved glycemic control was considered,
      significant reductions in diurnal systolic, diastolic and mean BP (102.3 +/- 6.0
      to 99.0 +/- 6.6 mmHg, P<0.05) were found. Acarbose monotherapy or combined with
      sulfonylurea was effective in improving glycemic control in hypertensive diabetic
      patients. Acarbose-induced improvement in metabolic control may reduce BP in
      these patients. Our data did not suggest a direct action of acarbose on insulin
      resistance or leptin levels.

PMID- 12185381
TI  - Measurement of the ultrasonic properties of human coronary arteries in vitro with
      a 50-MHz acoustic microscope.
AB  - Ultrasonic attenuation coefficient, wave propagation speed and integrated
      backscatter coefficient (IBC) of human coronary arteries were measured in vitro
      over the -6 dB frequency bandwidth (36 to 67 MHz) of a focused ultrasound
      transducer (50 MHz, focal distance 5.7 mm, f/number 1.7). Corrections were made
      for diffraction effects. Normal and diseased coronary artery sub-samples (N = 38)
      were obtained from 10 individuals at autopsy. The measured mean +/- SD of the
      wave speed (average over the entire vessel wall thickness) was 1581.04 +/- 53.88
      m/s. At 50 MHz, the average attenuation coefficient was 4.99 +/- 1.33 dB/mm with
      a frequency dependence term of 1.55 +/- 0.18 determined over the 36- to 67-MHz
      frequency range. The IBC values were: 17.42 +/- 13.02 (sr.m)-1 for thickened
      intima, 11.35 +/- 6.54 (sr.m)-1 for fibrotic intima, 39.93 +/- 50.95 (sr.m)-1 for
      plaque, 4.26 +/- 2.34 (sr.m)-1 for foam cells, 5.12 +/- 5.85 (sr.m)-1 for media
      and 21.26 +/- 31.77 (sr.m)-1 for adventitia layers. The IBC results indicate the
      possibility for ultrasound characterization of human coronary artery wall tissue
      layer, including the situations of diseased arteries with the presence of
      thickened intima, fibrotic intima and plaque. The mean IBC normalized with
      respect to the mean IBC of the media layer seems promising for use as a parameter
      to differentiate a plaque or a thickened intima from a fibrotic intima.

PMID- 12185382
TI  - Arterial blood pressure of term newborns during the first week of life.
AB  - The progressive behavior of the blood pressure of term newborns during the first
      week of life was assessed by the simultaneous use of oscillometric and Doppler
      methods. A total of 174 term neonates born at the Municipal Hospital Odilon
      Behrens in Belo Horizonte, from March 1996 to February 1997, were prospectively
      assessed. The oscillometric and Doppler ultrasonic methods were simultaneously
      used for four consecutive recordings obtained at 12 +/- 6, 24 +/- 6 and 72 +/- 24
      h and on the 7th +/- 1 day of life. The combined use of the two methods
      simplified the procedure, with automatic cuff inflation and deflation, and speed
      was properly controlled with an automatic pressure monitor. The procedure was
      performed using a Y-connection to the mercury sphygmomanometer, with blood
      pressure being recorded with an automatic device and systolic blood pressure
      being measured simultaneously by Doppler ultrasound. The newborns were awake, not
      crying and in the supine position. A statistically significant increase in
      systolic and diastolic blood pressure was observed between the first and second,
      and the third and fourth measurements by Doppler and oscillometric methods. No
      significant correlation between birth weight, length, ponderal index and blood
      pressure was observed. The technique used represents a simpler and more accurate
      procedure for blood pressure measurement.

PMID- 12185383
TI  - Presence of ductal carcinoma in situ confers an improved prognosis for patients
      with T1N0M0 invasive breast carcinoma.
AB  - We have retrospectively analyzed a series of 155 sequential cases of T1N0M0
      ductal carcinomas of which 51 tumors had a ductal carcinoma in situ (DCIS)
      component for correlation between the presence of DCIS and clinicopathological
      variables, recurrence and patient survival. No correlations between the presence
      of DCIS and age, menopausal status, size, estrogen or progesterone receptors were
      found. High-grade infiltrative tumors tended not to present a DCIS component (P =
      0.08). Patients with tumors associated with DCIS form a subgroup with few
      recurrences (P = 0.003) and good survival (P = 0.008). When tumors were
      classified by size, an association between large tumors (>1.0 cm) and increased
      recurrence and shortened overall survival was found. The presence of DCIS in this
      subgroup significantly reduced the relative risk of death.

PMID- 12185384
TI  - beta-Spectrin Sao PauloII, a novel frameshift mutation of the beta-spectrin gene
      associated with hereditary spherocytosis and instability of the mutant mRNA.
AB  - Hereditary spherocytosis (HS) is a common inherited anemia characterized by the
      presence of spherocytic red cells. Defects in several membrane protein genes have
      been involved in the pathogenesis of HS. beta-Spectrin-related HS seems to be
      common. We report here a new mutation in the beta-spectrin gene coding region in
      a patient with hereditary spherocytosis. The patient presented acanthocytosis and
      spectrin deficiency and, at the DNA level, a novel frameshift mutation leading to
      HS, i.e., a C deletion at codon 1392 (beta-spectrin Sao PauloII), exon 20. The
      mRNA encoding beta-spectrin Sao PauloII was very unstable and the mutant protein
      was not detected in the membrane or in other cellular compartments. It is
      interesting to note that frameshift mutations of the beta-spectrin gene at the 3'
      end allow the insertion of the mutant protein in the red cell membrane, leading
      to a defect in the auto-association of the spectrin dimers and consequent
      elliptocytosis. On the other hand, beta-spectrin Sao PauloII protein was absent
      in the red cell membrane, leading to spectrin deficiency, HS and the presence of
      acanthocytes.

PMID- 12185385
TI  - Toxicity to sea urchin egg development of the quinone fraction obtained from
      Auxemma oncocalyx.
AB  - Auxemma oncocalyx Taub. belongs to the Boraginaceae family and is native to the
      Brazilian northeast where it is known as "pau-branco". We investigated the
      ability of the water soluble fraction isolated from the heartwood of A. oncocalyx
      to inhibit sea urchin egg development. This fraction contains about 80%
      oncocalyxone A (quinone fraction), a compound known to possess strong cytotoxic
      and antitumor activities. In fact, the quinone fraction inhibited cleavage in a
      dose-dependent manner [IC50 of 18.4 (12.4-27.2) microg/ml, N = 6], and destroyed
      the embryos in the blastula stage [IC50 of 16.2 (13.7-19.2) microg/ml, N = 6]. We
      suggest that this activity is due to the presence of oncocalyxone A. In fact,
      these quinones present in A. oncocalyx extract have strong toxicity related to
      their antimitotic activity.

PMID- 12185386
TI  - Developmental norms for the Gardner Steadiness Test and the Purdue Pegboard: a
      study with children of a metropolitan school in Brazil.
AB  - Norms for the Gardner Steadiness Test and the Purdue Pegboard were developed for
      the neuropsychological assessment of children in the metropolitan area of Rio de
      Janeiro. A computer-generated unbiased sample of 346 children with a mean age of
      9.4 years (SD = 2.76), who were attending a large normal public school in this
      urban area, was the subject of this study. Two boys were removed from the study,
      one for refusing to participate and the other due to severe strabismus.
      Therefore, the final sample contained 344 children (173 boys and 171 girls). Sex
      and age of the child and hand preferred for writing, but not ethnic membership or
      social class, had significant effects on performance in the Gardner Steadiness
      Test and the Purdue Pegboard. Girls outperformed boys. Older children performed
      better than younger children. However, the predictive relationship between age of
      the child and neuropsychological performance included linear and curvilinear
      components. Comparison of the present results to data gathered in the United
      States revealed that the performance of this group of Brazilian children is
      equivalent to that of US children after Bonferroni's correction of the alpha
      level of significance. It is concluded that sex and age of the child and hand
      preferred for writing should be taken into account when using the normative data
      for the two instruments evaluated in the present study. Furthermore, the
      relevance of neurobehavioral antidotes for the obliteration of some of the
      probable neuropsychological effects of cultural deprivation in Brazilian public
      school children is hypothesized.

PMID- 12185387
TI  - Adrenoceptors of the medial septal area modulate water intake and renal excretory
      function induced by central administration of angiotensin II.
AB  - We investigated the role of alpha-adrenergic antagonists and clonidine injected
      into the medial septal area (MSA) on water intake and the decrease in Na+, K+ and
      urine elicited by ANGII injection into the third ventricle (3rdV). Male Holtzman
      rats with stainless steel cannulas implanted into the 3rdV and MSA were used.
      ANGII (12 nmol/ micro l) increased water intake (12.5 +/- 1.7 ml/120 min).
      Clonidine (20 nmol/ micro l) injected into the MSA reduced the ANGII-induced
      water intake (2.9 +/- 0.5 ml/120 min). Pretreatment with 80 nmol/ micro l
      yohimbine or prazosin into the MSA also reduced the ANGII-induced water intake
      (3.0 +/- 0.4 and 3.1 +/- 0.2 ml/120 min, respectively). Yohimbine + prazosin +
      clonidine injected into the MSA abolished the ANGII-induced water intake (0.2 +/-
      0.1 and 0.2 +/- 0.1 ml/120 min, respectively). ANGII reduced Na+ (23 +/- 7 micro
      Eq/120 min), K+ (27 +/- 3 micro Eq/120 min) and urine volume (4.3 +/- 0.9 ml/120
      min). Clonidine increased the parameters above. Clonidine injected into the MSA
      abolished the inhibitory effect of ANGII on urinary sodium. Yohimbine injected
      into the MSA also abolished the inhibitory effects of ANGII. Yohimbine +
      clonidine attenuated the inhibitory effects of ANGII. Prazosin injected into the
      MSA did not cause changes in ANGII responses. Prazosin + clonidine attenuated the
      inhibitory effects of ANGII. The results showed that MSA injections of alpha1-
      and alpha2-antagonists decreased ANGII-induced water intake, and abolished the
      Na+, K+ and urine decrease induced by ANGII into the 3rdV. These findings suggest
      the involvement of septal alpha1- and alpha2-adrenergic receptors in water intake
      and electrolyte and urine excretion induced by central ANGII.

PMID- 12185389
TI  - The attentional modulation of the flash-lag effect.
AB  - If a dot is flashed in perfect alignment with a pair of dots rotating around the
      visual fixation point, most observers perceive the rotating dots as being ahead
      of the flashing dot (flash-lag effect). This perceptual effect has been
      interpreted to result from the perceptual extrapolation of the moving dots, the
      differential visual latencies between flashing and moving stimuli, as well as the
      modulation of attentional mechanisms. Here we attempted to uncouple the
      attentional effects brought about by the spatial predictability of the flashing
      dot from the sensory effects dependent on its visual eccentricity. The stimulus
      was a pair of dots rotating clockwise around the fixation point. Another dot was
      flashed at either the upper right or the lower left of the visual field according
      to three separate blocked situations: fixed, alternate and random positions.
      Twenty-four participants had to judge, in all three situations, the location of
      the rotating dots in relation to the imaginary line connecting the flashing dot
      and the fixation point at the moment the dot was flashed. The flash-lag effect
      was observed in all three situations, and a clear influence of the spatial
      predictability of the flashing dot on the magnitude of the perceptual phenomenon
      was revealed, independently of sensory effects related to the eccentricity of the
      stimulus in the visual field. These findings are consistent with our proposal
      that, in addition to sensory factors, the attentional set modulates the magnitude
      of the differential latencies that give rise to the flash-lag phenomenon.

PMID- 12185388
TI  - Smoking and psychiatric disorders: a comorbidity survey.
AB  - Epidemiological and clinical studies have shown a positive correlation between
      smoking and psychiatric disorders. To investigate the prevalence of cigarette
      smoking, 277 psychiatric outpatients with anxiety or depressive disorders (DSM
      IV) answered a self-evaluation questionnaire about smoking behavior and were
      compared with a group of 68 control subjects. The diagnoses (N = 262) were: 30.2%
      (N = 79) major depressive disorder, 23.3% (N = 61) panic disorder, 15.6% (N = 41)
      social anxiety disorder, 7.3% (N = 19) other anxiety disorders, and 23.7% (N =
      62) comorbidity disorders. Among them, 26.3% (N = 69) were smokers, 23.7% (N =
      62) were former smokers and 50.0% (N = 131) were nonsmokers. The prevalence of
      nicotine dependence among the smokers was 59.0% (DSM-IV). The frequency of
      cigarette smoking did not show any significant difference among the five classes
      of diagnosis. The social anxiety disorder patients were the heaviest smokers
      (75.0%), with more unsuccessful attempts to stop smoking (89.0%). The frequency
      of former smokers was significantly higher among older subjects and nonsmokers
      were significantly younger (chi2 = 9.13, d.f. = 2, P = 0.01). Our data present
      some clinical implications suggesting that in our psychiatric outpatient sample
      with anxiety disorder, major depression and comorbidity (anxiety disorder and
      major depression), the frequency of cigarette smoking did not differ from the
      frequency found in the control group or in general population studies. Some
      specific features of our population (outpatients, anxiety and depressive
      disorders) might be responsible for these results.

PMID- 12185390
TI  - Differential expression of AMPA-type glutamate receptor subunits during
      development of the chick optic tectum.
AB  - Glutamate receptors have been often associated with developmental processes. We
      used immunohistochemical techniques to evaluate the expression of the AMPA-type
      glutamate receptor (GluR) subunits in the chick optic tectum (TeO). Chick embryos
      from the 5th through the 20th embryonic day (E5-E20) and one-day-old (P1) chicks
      were used. The three types of immunoreactivity evaluated (GluR1, GluR2/3, and
      GluR4) had different temporal and spatial expression patterns in the several
      layers of the TeO. The GluR1 subunit first appeared as moderate staining on E7
      and then increased on E9. The mature GluR1 pattern included intense staining only
      in layer 5 of the TeO. The GluR2/3 subunits presented low expression on E5, which
      became intense on E7. The staining for GluR2/3 changed to very intense on E14 in
      tectal layer 13. Staining of layer 13 neurons is the most prominent feature of
      GluR immunoreactivity in the adult TeO. The GluR4 subunit generally presented the
      lowest expression starting on E7, which was similar to the adult pattern. Some
      instances of transient expression of GluR subunits were observed in specific cell
      populations from E9 through E20. These results demonstrate a differential
      expression of the GluR subunits in the embryonic TeO, adding information about
      their possible functions in the developmental processes of the visual system.

PMID- 12185391
TI  - Modulation of the perception of temporal order by attentional and pre-attentional
      factors.
AB  - When two stimuli are presented simultaneously to an observer, the perceived
      temporal order does not always correspond to the actual one. In three experiments
      we examined how the location and spatial predictability of visual stimuli
      modulate the perception of temporal order. Thirty-two participants had to report
      the temporal order of appearance of two visual stimuli. In Experiment 1, both
      stimuli were presented at the same eccentricity and no perceptual asynchrony
      between them was found. In Experiment 2, one stimulus was presented close to the
      fixation point and the other, peripheral, stimulus was presented in separate
      blocks in two eccentricities (4.8 degrees and 9.6 degrees ). We found that the
      peripheral stimulus was perceived to be delayed in relation to the central one,
      with no significant difference between the delays obtained in the two
      eccentricities. In Experiment 3, using three eccentricities (2.5 degrees, 7.3
      degrees and 12.1 degrees ) for the presentation of the peripheral stimulus, we
      compared a condition in which its location was highly predictable with two other
      conditions in which its location was progressively less predictable. Here, the
      perception of the peripheral stimulus was also delayed in relation to the central
      one, with this delay depending on both the eccentricity and predictability of the
      stimulus. We argue that attentional deployment, manipulated by the spatial
      predictability of the stimulus, seems to play an important role in the temporal
      order perception of visual stimuli. Yet, under whichever condition of spatial
      predictability, basic sensory and attentional processes are unavoidably entangled
      and both factors must concur to the perception of temporal order.

PMID- 12185392
TI  - Daily birth numbers in Passo Fundo, South Brazil, 1997-1999: trends and
      periodicities.
AB  - Between October 6, 1997 and April 30, 1999, 5011 births (mean: 8.76 per day) were
      registered in the city of Passo Fundo, South Brazil. The sequence of 572 daily
      birth numbers was not random (iteration test). Neyman distribution (m = yen )
      showed the best fit. Clusters of days with higher birth numbers alternated with
      days with low numbers of births. Periodogram analysis revealed a significant
      periodicity of 6.98 days. The cosinor regression, testing 10 a priori supposed
      period lengths, found significant seasonality peaking in August-September and
      significantly highest birth numbers on Thursdays. Among the lunar and solar
      rotation cycles, the tropic lunar cycle and its 4th harmonic were most
      pronounced, in agreement with results concerning natality in Germany obtained by
      Svante Arrhenius in the 19th century. These findings confirm Derer-Halberg's
      concept of multiseptans. In addition to cycling, a significantly increasing
      linear trend with a daily increase of 0.0045 births was encountered. This
      documents a growth of the population in agreement with national statistical data.

PMID- 12185393
TI  - Heart rate recovery after exercise: relations to heart rate variability and
      complexity.
AB  - Physical exercise is associated with parasympathetic withdrawal and increased
      sympathetic activity resulting in heart rate increase. The rate of post-exercise
      cardiodeceleration is used as an index of cardiac vagal reactivation. Analysis of
      heart rate variability (HRV) and complexity can provide useful information about
      autonomic control of the cardiovascular system. The aim of the present study was
      to ascertain the association between heart rate decrease after exercise and HRV
      parameters. Heart rate was monitored in 17 healthy male subjects (mean age: 20
      years) during the pre-exercise phase (25 min supine, 5 min standing), during
      exercise (8 min of the step test with an ascending frequency corresponding to 70%
      of individual maximal power output) and during the recovery phase (30 min
      supine). HRV analysis in the time and frequency domains and evaluation of a newly
      developed complexity measure - sample entropy - were performed on selected
      segments of heart rate time series. During recovery, heart rate decreased
      gradually but did not attain pre-exercise values within 30 min after exercise. On
      the other hand, HRV gradually increased, but did not regain rest values during
      the study period. Heart rate complexity was slightly reduced after exercise and
      attained rest values after 30-min recovery. The rate of cardiodeceleration did
      not correlate with pre-exercise HRV parameters, but positively correlated with
      HRV measures and sample entropy obtained from the early phases of recovery. In
      conclusion, the cardiodeceleration rate is independent of HRV measures during the
      rest period but it is related to early post-exercise recovery HRV measures,
      confirming a parasympathetic contribution to this phase.

PMID- 12185394
TI  - Commentary on "clinical studies on the mechanism of action of clozapine; the
      dopamine-serotonin hypothesis of schizophrenia." Psychopharmacology (1989) 99:S18
      S27.

PMID- 12185395
TI  - Repeated cocaine decreases the avoidance response to a novel aversive stimulus in
      rats.
AB  - RATIONALE: Stress interacts with cocaine to produce enhanced neurochemical and
      behavioral responding to cocaine; however, few studies have examined
      unconditioned behavioral responses to aversive stimuli after repeated cocaine.
      OBJECTIVES. Studies were conducted to measure the approach/avoidance response to
      an aversive stimulus after repeated cocaine treatment in male and female rats.
      METHODS: An unconditioned approach/avoidance task was used in which rats were
      placed into a box with a novel, aversive stimulus (formaldehyde; Form), and place
      aversion was assessed. RESULTS: Initial studies established a dose-response curve
      using different concentrations of Form, and also determined that avoidance of
      Form was abolished by pretreatment with an anxiolytic dose of chlordiazepoxide.
      To examine the effects of prior cocaine treatment, intact or gonadectomized male
      and female rats were pretreated with daily saline or cocaine (15 mg/kg, IPx5
      days), and their approach/avoidance response to Form was tested 4-7 days later.
      In intact males, cocaine decreased the avoidance of Form, and previous
      gonadectomy completely abolished this response. Decreased avoidance behavior did
      not appear to be linked to behavioral sensitization to cocaine, since
      gonadectomized males demonstrated locomotor sensitization when given subsequent
      cocaine challenge. In females, avoidance of Form was not altered by either
      cocaine or gonadectomy. Three experiments further characterized the
      approach/avoidance response to Form in males. In the first experiment, daily
      footshock stress did not significantly alter the avoidance of Form. In a second
      study, rats that displayed high and low locomotor responses to a novel cage
      showed no differences between groups in their avoidance of Form. In the third
      experiment, intra-nucleus accumbens microinjection of fluphenazine (5 micro
      g/side) attenuated the daily cocaine-induced decrease in avoidance of Form.
      CONCLUSIONS: These studies demonstrate that gonadal hormones may mediate cocaine
      induced alterations in approach/avoidance to an aversive stimulus in males, and
      suggest that testosterone may act centrally to modulate dopamine responsiveness
      in the nucleus accumbens.

PMID- 12185396
TI  - Citalopram dose-response revisited using an alternative psychometric approach to
      evaluate clinical effects of four fixed citalopram doses compared to placebo in
      patients with major depression.
AB  - RATIONALE: Among the many problems in interpreting dose-response studies with
      antidepressants are the psychometric problems in the identification of true
      antidepressive effect versus true adverse drug effect. OBJECTIVES: This study is
      a re-examination of a dose-response trial with citalopram in order to examine the
      explanatory ability of using strict psychometric dimensions to measure the wanted
      and unwanted drug effects of different doses compared to placebo. METHODS: The
      antidepressive response was measured after 2 and 6 weeks of therapy with the
      depression subscales of the HAM-D and on the Montgomery-Asberg Depression Scale
      (MADRS). The patient-reported Symptom Checklist (SCL) sub-scales for depression
      and anxiety were also examined. Subjective side-effects were measured on
      serotonin-specific items of the SCL. Effect size statistics were used to measure
      the antidepressive effect (an effect size of 0.30 equals a drug superiority over
      placebo of 15-20%). Side effects were statistically analysed using baseline
      adjusted scores of the individual symptoms. RESULTS: The psychometric analysis of
      the outcome scales showed that the full HAM-D(17), the SCL-56 and the SCL side
      effect subscale were multidimensional scales, while the HAM-D and MADRS subscales
      as well as the SCL-anxiety subscale were most homogeneous, indicating that their
      total scores are sufficient statistics. When the scales were used as well as the
      individual serotonin-specific SCL side-effect symptoms, the results showed that
      after 2 weeks of therapy a clinical response (effect side over 0.30) was only
      seen for the SCL-anxiety subscale in the citalopram doses of 40 mg and 60 mg
      daily. After 6 weeks of therapy response to even 10 mg and 20 mg was seen in the
      HAM-D and MADRS subscales and in the SCL-anxiety subscale, however, with lower
      effect sizes than found for 40 mg and 60 mg citalopram daily. The dose of 20 mg
      citalopram induced side-effects comparable with those seen for 40 mg and 60 mg,
      while 10 mg was not different from placebo. This was further confirmed by the
      fact that more patients dropped out on 20 mg than on 10 mg citalopram daily, due
      to adverse events. CONCLUSION: This psychometric re-examination of a citalopram
      dose-response trial has shown that the pure antidepressive or antianxiety effects
      can be observed after 6 weeks of therapy even in a dose of 10 mg daily. However,
      both 10 mg and 20 mg daily had lower effect sizes than 40 mg and 60 mg daily. At
      a dose level of 20 mg daily, side effects are more pronounced initially than at
      10 mg daily; this should be taken into account clinically when evaluating the
      overall benefit of the drug. For a highly serotonin-specific drug such as
      citalopram, both wanted and unwanted effects are dose-related.

PMID- 12185397
TI  - The antidepressant-like effect induced by the sigma(1) (sigma(1)) receptor
      agonist igmesine involves modulation of intracellular calcium mobilization.
AB  - RATIONALE: Activation of the neuronal sigma(1) (sigma(1)) receptor potentiates
      calcium mobilization, leading to effective modulation of postsynaptic responses
      to neurotransmitters. At the behavioral level, sigma(1) agonists modulate
      learning, response to stress and depression. In particular, the selective
      sigma(1) agonist igmesine reduced immobility in the forced swimming test.
      OBJECTIVES AND METHODS: We investigated the effect of modulators of Ca(2+) influx
      and mobilization, administered intracerebroventricularly at doses ineffective
      alone, on the igmesine effect. The tricyclic antidepressant desipramine was also
      studied for comparison. RESULTS: The calcium chelator EGTA blocked both igmesine
      and desipramine-induced decreases of immobility duration, indicating the
      importance of extracellular Ca(2+) influx in the initial action of each compound.
      Both L- and N-type voltage-dependent calcium channel (VDCC) appeared involved in
      the sigma(1) agonist effect. Verapamil, an L-type VDCC antagonist or omega
      conotoxin GVI, a N-type VDCC antagonist, blocked whereas (-)-Bay K8644, a L-type
      VDCC agonist, potentiated the igmesine effect. Mobilization of intracellular
      Ca(2+) stores is involved selectively in the effect mediated by the sigma(1)
      receptor, since the membrane permeable intracellular Ca(2+) chelator EGTA/AM
      affected only the igmesine effect. Inositol 1,4,5-trisphosphate (InsP(3))
      receptor-sensitive Ca(2+) pools appeared primarily involved, rather than
      Ca(2+)/caffeine-sensitive Ca(2+) pools. Indeed, the InsP(3) receptor positive
      modulator bradykinin potentiated, whereas the InsP(3) receptor antagonist
      xestospongin C blocked the igmesine effect. The ryanodine receptor agonist
      caffeine failed to affect the efficacy of igmesine, whereas the antagonist
      ryanodine reduced it. CONCLUSIONS: The sigma(1) receptor-mediated behavioral
      effect is dependent not only on rapid Ca(2+) influx, as observed for a classical
      antidepressant, but also on intracellular Ca(2+) mobilization.

PMID- 12185398
TI  - A comparison of the effects of a beta-adrenergic blocker and a benzodiazepine
      upon the recognition of human facial expressions.
AB  - RATIONALE: Accumulating evidence from neuropsychological and neuroimaging
      research suggests that facial expressions are processed by at least partially
      separable neurocognitive systems. Recent evidence implies that the processing of
      different facial expressions may also be dissociable pharmacologically by
      GABAergic and noradrenergic compounds, although no study has directly compared
      the two types of drugs. OBJECTIVE: The present study therefore directly compared
      the effects of a benzodiazepine with those of a beta-adrenergic blocker on the
      ability to recognise emotional expressions. METHODS: A double-blind, independent
      group design was used with 45 volunteers to compare the effects of diazepam (15
      mg) and metoprolol (50 mg) with matched placebo. Participants were presented with
      morphed facial expression stimuli and asked to identify which of the six basic
      emotions (sadness, happiness, anger, disgust, fear and surprise) were portrayed.
      Control measures of mood, pulse rate and word recall were also taken. RESULTS:
      Diazepam selectively impaired participants' ability to recognise expressions of
      both anger and fear but not other emotional expressions. Errors were mainly
      mistaking fear for surprise and disgust for anger. Metoprolol did not
      significantly affect facial expression recognition. CONCLUSIONS: These findings
      are interpreted as providing further support for the suggestion that there are
      dissociable systems responsible for processing emotional expressions. The results
      may have implications for understanding why 'paradoxical' aggression is sometimes
      elicited by benzodiazepines and for extending our psychological understanding of
      the anxiolytic effects of these drugs.

PMID- 12185399
TI  - The effects of tryptophan depletion on cognitive and affective processing in
      healthy volunteers.
AB  - RATIONALE: Cognitive impairment is a common feature of depressive illness. While
      accumulating evidence suggests that brain serotonin (5-HT) pathways play an
      important role in the neurobiology of depression, the extent to which altered 5
      HT function is responsible for the associated changes in cognition and emotion
      remains unclear. OBJECTIVE: The present study examined the effects of acute
      dietary depletion of tryptophan (TRP) on cognitive and affective processing in
      healthy volunteers and explored the putative role of 5-HT in the neuropsychology
      of depression. METHODS: We administered computerised cognitive tests to healthy
      control participants following ingestion of TRP-free and nutritionally balanced
      amino acid drinks in a double-blind, placebo-controlled, crossover design.
      RESULTS: The TRP-free amino acid mixture significantly lowered plasma total and
      free TRP concentrations relative to baseline values and produced selective
      deficits similar to those observed previously in cases of clinical depression. In
      particular, TRP depletion increased response times for happy but not sad targets
      in an affective go/no-go task and slowed responding in a visual discrimination
      and reversal learning task. These deficits were not due to a global sedative
      effect, as planning ability was unimpaired. CONCLUSIONS: The present data
      indicate that serotonergic factors may be more involved in the disrupted
      inhibitory and emotional processing characteristic of depression than in other
      aspects of executive function, such as planning ability. These findings support
      the recent proposal that serotonergic manipulation may have greater effects on
      tasks mediated by frontal circuitry that includes the orbitofrontal cortex than
      by dorsolateral prefrontal cortex circuitry.

PMID- 12185400
TI  - Cocaine-induced locomotor activity and cocaine discrimination in dopamine D2
      receptor mutant mice.
AB  - RATIONALE: Dopamine (DA) D2-like antagonists block several effects of cocaine,
      including its locomotor stimulant and interoceptive discriminative-stimulus
      effects. Because these compounds generally lack selectivity among the D2-like DA
      receptors, the specific roles of the subtypes remain unclear. OBJECTIVES: DA D2
      receptor knockout (DA D2R KO), heterozygous (HET), and wild-type (WT) mice were
      used to study the role of D2 DA receptors in the effects of cocaine. Some effects
      of the relatively selective DA D2-like antagonist raclopride were also studied to
      further assess the role of D2 receptors. METHODS: DA D2R KO, HET, and WT mice
      were treated with cocaine (1-10 mg/kg) or vehicle, and their horizontal locomotor
      activity was assessed. The mice were also trained to discriminate i.p. injections
      of saline from cocaine (10 mg/kg) using a two-response key, fixed-ratio-20
      response, food-reinforcement procedure. A range of doses of cocaine (1.0-17
      mg/kg) was administered before 15-min test sessions. RESULTS: Both DA D2R KO and
      HET mice showed reduced levels of horizontal activity relative to WT mice.
      Cocaine dose dependently stimulated activity in each genotype, with the highest
      level of activity induced in the DA D2R WT mice. All three genotypes acquired the
      discrimination of 10 mg/kg cocaine; tested doses of 1.0-10.0 mg/kg produced dose
      related increases in the number of cocaine-appropriate responses. Raclopride, at
      inactive to fully active doses (0.1-1.0 mg/kg), did not fully substitute for
      cocaine. Raclopride dose dependently shifted the cocaine dose-effect curve to the
      right in DA D2R WT and HET mice. However, in DA D2R KO mice, raclopride was
      inactive as an antagonist. CONCLUSIONS: The present data indicate an involvement
      of D2 DA receptors in the locomotor-stimulating effects and the interoceptive
      discriminative-stimulus effects of cocaine in WT subjects. However, the D2
      receptor is not necessary for the effects, suggesting redundant dopaminergic
      mechanisms for the discriminative-stimulus interoceptive effects of cocaine.

PMID- 12185401
TI  - Dopamine and human information processing: a reaction-time analysis of the effect
      of levodopa in healthy subjects.
AB  - RATIONALE: Dopamine is involved in a variety of motor and non-motor information
      processing operations. One way to determine its contribution to human information
      processing is to study reaction time (RT) performance after oral absorption of
      its precursor, levodopa, which increases its concentration in the nervous system.
      OBJECTIVE: The purpose of the present study was to investigate the effect of a
      single dose of levodopa on information processing in healthy human subjects using
      the additive-factor method. After oral absorption of a single dose of levodopa
      (200 mg) or a placebo (randomized, double-blind, cross-over design), eight adults
      (aged 21-28 years, mean 25 years) performed a two-choice visual RT task. Signal
      intensity, stimulus-response mapping and foreperiod duration were manipulated.
      RESULTS: The effects of these three variables were found additive on RT,
      indicating that that three independent stages - namely, stimulus preprocessing,
      response selection and motor adjustment - were manipulated. Levodopa improved RT
      performance in a specific way: it interacted with signal intensity but its effect
      was additive with those of stimulus-response mapping and foreperiod duration.
      CONCLUSION: These results show that levodopa specifically affects the stimulus
      preprocessing stage, which suggests that the dopaminergic system plays a role in
      sensory processing, possibly by acting on the level of arousal.

PMID- 12185402
TI  - The effects of sub-chronic administration of hydrocortisone on hormonal and
      psychological responses to L-tryptophan in normal male volunteers.
AB  - RATIONALE: 5-Hydroxytryptamine(1A) (5-HT(1A)) receptor function has been shown to
      be attenuated by corticosteroid hormones in a variety of animal experimental
      paradigms. It has been suggested that this effect may be central to the
      pathophysiology of severe depressive illness in humans, a condition in which 5
      HT(1A) receptor function is reduced and corticosteroid hormone levels are
      elevated. Evidence suggests that the hormonal response to L-tryptophan ( L-TRP)
      is mediated by 5-HT(1A) receptors. This response has been shown to be reduced
      following acute administration of hydrocortisone, and we hypothesised that sub
      chronic administration of hydrocortisone would also blunt it. OBJECTIVES: To
      examine the effects of sub-chronic administration of hydrocortisone on hormonal
      and psychological responses to L-TRP infusion in healthy male subjects. To
      ascertain whether cortisol was exerting effects on prolactin release directly at
      the pituitary rather than via hypothalamic 5-HT(1A) receptors, a thyroid
      releasing hormone (TRH) challenge test was performed. METHODS: Fourteen healthy
      male volunteers took part in a random-order, double-blind, placebo-controlled
      study, in which 20 mg hydrocortisone or placebo was administered twice daily for
      7 days before infusion of L-TRP. A TRH challenge was administered to eight of the
      subjects following the L-TRP infusion. RESULTS: Pre-treatment with hydrocortisone
      significantly reduced the growth hormone (GH) and cortisol responses, but not the
      prolactin (PRL) response to the infusion. TRH administration caused a robust
      increase in PRL, but this response was not attenuated by hydrocortisone pre
      treatment. The TSH response to TRH was blunted. There was no effect of pre
      treatment on psychological responses to L-TRP. CONCLUSIONS: The attenuation in GH
      response following hydrocortisone pre-treatment could indicate a reduction in 5
      HT(1A) receptor function, although it is probable that it is attributable to the
      action of hydrocortisone at the pituitary level. More precise, non-neuroendocrine
      models of 5-HT(1A) receptor function are necessary to clarify this.

PMID- 12185403
TI  - Effects of the D(3) dopamine receptor antagonist, U99194A, on brain stimulation
      and d-amphetamine reward, motor activity, and c-fos expression in ad libitum fed
      and food-restricted rats.
AB  - RATIONALE: Previous studies indicate that the D(3) dopamine (DA) receptor is
      preferentially expressed in limbic forebrain DA terminal areas and may mediate
      functional effects opposite those of the D(1) and D(2) receptor types. However,
      the locations of the D(3) receptors that regulate behavior, and the range of
      behavioral functions regulated, are not clear. OBJECTIVE: The objective of this
      study was to evaluate behavioral and cellular effects of the preferential D(3)
      dopamine receptor antagonist, U99194A. METHODS: In experiment 1, the rewarding
      effect of U99194A (5.0, 10.0 and 20.0 mg/kg, SC) was measured in terms of its
      ability to lower the threshold for lateral hypothalamic self-stimulation (LHSS)
      in ad libitum fed rats. To amplify a possibly weak reward signal, testing was
      also conducted in food-restricted rats. The ability of U99194A to alter the
      threshold-lowering effect of d-amphetamine was also assessed. In experiment 2,
      effects of U99194A on horizontal and vertical motor activity were compared in ad
      libitum fed and food-restricted rats. In experiment 3, effects of a behaviorally
      active dose of U99194A (5.0 mg/kg) on brain c-fos expression were measured and
      compared to those produced by d-amphetamine (0.5 mg/kg, IP). In experiment 4, the
      motor and cellular activating effects of U99194A were challenged with the D(1)
      dopamine receptor antagonist, SCH-23390 (0.1 mg/kg). RESULTS: U99194A displayed
      no rewarding efficacy in the LHSS paradigm. U99194A did, however, augment the
      rewarding effect of d-amphetamine. U99194A also produced a motor activating
      effect, reversible by SCH-23390, which was greater in food-restricted than ad
      libitum fed rats. The pattern and intensity of fos-like immunoreactivity (FLI)
      induced by U99194A was similar to that produced by d-amphetamine and was blocked,
      in caudate-putamen and nucleus accumbens, by SCH-23390. CONCLUSIONS: These
      results indicate that U99194A has psychostimulant-like effects on motor activity
      and striatal c-fos expression that are dependent upon the D(1) DA receptor.
      However, doses of U99194A that are adequate to stimulate motor activity and c-fos
      expression in striatal and limbic structures do not possess direct rewarding
      effects in the LHSS paradigm. Overall, these results seem consistent with the
      hypothesis that D(3) antagonism enhances D(1)/D(2) mediated signaling with
      behavioral effects dependent on both the density of D(3) receptors and the
      prevailing level of DA transmission in particular brain regions.

PMID- 12185404
TI  - Postsynaptic 5-HT(1A) receptors mediate an increase in locomotor activity in the
      monoamine-depleted rat.
AB  - RATIONALE: In animal models of reduced dopamine transmission, such as haloperidol
      induced catalepsy or monoamine-depleted animals, serotonin (5-hydroxytryptamine;
      5-HT) 5-HT(1A) agonists appear to enhance motor activity. However, the exact
      mechanism remains unclear. OBJECTIVE: The objective of the present study was to
      demonstrate that 5-HT(1A) agonists can increase locomotor activity by activation
      of postsynaptic 5-HT(1A) heteroreceptors without the involvement of
      somatodendritic 5-HT(1A) autoreceptors which are known to regulate 5-HT neuronal
      activity. METHODS: The effects of the 5-HT(1A) full agonist R-(+)-8-hydroxy-2-(di
      n-propylamino)tertralin ( R-(+)-8-OHDPAT) on locomotor activity in reserpinized
      (i.e., monoamine-depleted) rats were studied. RESULTS: The present data
      demonstrate that R-(+)-8-OHDPAT significantly increased locomotor activity in
      monoamine-depleted animals at a dose as low as 0.01 mg/kg. The partial 5-HT(1A)
      agonist/D(2) antagonist buspirone (3 mg/kg) also elevated locomotor activity. The
      effects of these 5-HT(1A) compounds were found to be similar to the locomotor
      stimulating effect of the dopamine precursor 3,4-dihydroxyphenylalanine (150
      mg/kg, 15 min after 50 mg/kg benserazide). The 5-HT(1A) antagonist N-[2-[4-(2
      methoxyphenyl)-1-piperazinyl]ethyl]-N-2-pyridinyl-cyclohexanecarboxamide maleate
      (WAY 100635; 0.2 mg/kg) blocked the R-(+)-8-OHDPAT (0.03 mg/kg)-mediated increase
      in locomotion. Blockade of 5-HT synthesis with DL- p-chlorophenylalanine (pCPA),
      a tryptophan hydroxylase inhibitor, prior to reserpinization did not affect R-(+)
      8-OHDPAT-induced locomotion. CONCLUSIONS: The present data indicate that R-(+)-8
      OHDPAT can increase motor activity in monoamine-depleted rats through
      postsynaptic 5-HT(1A) receptors and not necessarily through 5-HT(1A) autoreceptor
      mediated alterations in 5-HT synthesis and release. A potential mechanism of 5
      HT(1A)-mediated modulation of non-monoaminergic motor circuits in the brain is
      discussed. Taken together, the results suggest that 5-HT(1A) agonists would
      provide a novel approach to the amelioration of antipsychotic-induced side
      effects and the symptomatic treatment of Parkinson's disease.

PMID- 12185405
TI  - The influence of mirtazapine on anterior pituitary hormone secretion in healthy
      male subjects.
AB  - RATIONALE: Unlike other antidepressants, mirtazapine does not inhibit the
      reuptake of norepinephrine or serotonin but acts as an antagonist at presynaptic
      alpha(2) receptors, at postsynaptic 5-HT(2) and 5-HT(3) receptors, and at
      histaminergic H(1) receptors. This special mechanism of action may be
      characterized by a distinct pharmacoendocrinological profile. OBJECTIVES: In the
      present investigation the influence of acute oral administration of 15 mg
      mirtazapine on the cortisol (COR), corticotropin (ACTH), growth hormone (GH), and
      prolactin (PRL) secretion was examined in six healthy male subjects, compared to
      placebo. METHODS: After insertion of an intravenous catheter, both the mean
      arterial blood pressure (MAP) and the heart rate were recorded and blood samples
      were drawn 1 h prior to the administration of mirtazapine or placebo (7:00 a.m.),
      at time of application (8:00 a.m.), and thereafter every hour up to 8:00 p.m.
      Concentrations of COR, ACTH, GH, and PRL were measured in each blood sample by
      double-antibody radioimmunoassay and chemiluminescence immunoassay methods. The
      area under the curve (AUC) was used as parameter for the COR, ACTH, GH, and PRL
      response. Furthermore, the urinary free cortisol excretion (UFC) was determined
      beginning at 8:00 a.m. (time of application of placebo or mirtazapine) up to 8:00
      a.m. the day after. RESULTS: Multivariate analyses of variance revealed
      significantly lower COR AUC, ACTH AUC, and UFC values after 15 mg mirtazapine
      compared to placebo, whereas no differences were found with respect to GH and PRL
      stimulation, MAP, and heart rate. CONCLUSIONS: Since the acute inhibition of COR
      secretion in the healthy volunteers was paralleled by a simultaneous decrease of
      ACTH release, central mechanisms (for example, inhibition of hypothalamic CRH
      output) are suggested to be responsible for the inhibitory effects of mirtazapine
      on COR secretion. Our results are of particular interest in the light of the
      hypercortisolism observed in depressed patients and new pharmacological
      approaches such as CRH(1) receptor antagonists.

PMID- 12185406
TI  - Bupropion occupancy of the dopamine transporter is low during clinical treatment.
AB  - RATIONALE: Bupropion is thought to treat major depression by blocking the
      dopamine transporter (DAT) because bupropion appears to have a selective affinity
      for the DAT. The validity of this mechanism has been questioned because the
      affinity of bupropion for the DAT is quite low. OBJECTIVE: To determine the
      occupancy of bupropion for the DAT during clinical treatment of patients with
      depression. METHODS: Positron emission tomography with [(11)C]-RTI32 was used to
      determine the striatal DAT binding potential (BP) of eight depressed patients
      before and during treatment with bupropion. BP is proportional to available
      receptor density (receptors not blocked by drug). Occupancy is the percent change
      in BP. Eight healthy subjects were similarly studied in a test-retest design.
      RESULTS: No significant difference in DAT BP was found after bupropion treatment
      in comparison to the test-retest data. The occupancy after bupropion treatment
      was 14% (confidence interval 6-22%) as compared to 7% in the test-retest
      condition. CONCLUSIONS: Bupropion treatment occupies less than 22% of DAT sites.
      This raises the question as to whether a DAT occupancy of less than 22% is
      therapeutic or whether there is another mechanism involved during treatment with
      bupropion.

PMID- 12185407
TI  - Acute administration of citalopram facilitates memory consolidation in healthy
      volunteers.
AB  - OBJECTIVES: Decreasing serotonergic neurotransmission in humans has been found to
      impair memory consolidation. Such effects may be relevant to the memory deficits
      seen in major depression and the cognitive actions of antidepressant drugs used
      to treat them. However, the improvement in cognitive function often found
      following successful pharmacological treatment in depression may be confounded by
      symptom improvement. RATIONALE: The present study assessed the effects of an
      acute challenge with the selective serotonergic re-uptake inhibitor citalopram in
      healthy (non-depressed) females. METHODS: Immediate and delayed
      recall/recognition was assessed using the auditory verbal learning test following
      10 mg (intravenous) citalopram or placebo in a double-blind between groups
      design. RESULTS: Immediate recall on the verbal memory test was unaffected by
      citalopram administration. However, volunteers receiving citalopram showed
      enhanced long-term memory performance in terms of delayed recall and recognition
      relative to those receiving placebo. Sustained attention performance was also
      comparable in the two groups of subjects suggesting that non-specific increases
      in information processing are not responsible for this effect. CONCLUSIONS: These
      results indicate that augmentation of serotonergic neurotransmission is
      associated with increased memory consolidation, which may be relevant to its
      therapeutic and cognitive actions in acutely depressed patients.

PMID- 12185408
TI  - Involvement of the opioid system in the anxiolytic-like effects induced by
      Delta(9)-tetrahydrocannabinol.
AB  - RATIONALE: Recent studies have shown that several pharmacological actions induced
      by cannabinoids, including antinociception and reward, involve the participation
      of the endogenous opioid system. OBJECTIVES: The present study was designed to
      examine the possible involvement of the different opioid receptors in the
      anxiolytic-like responses induced by Delta(9)-tetrahydrocannabinol (THC).
      METHODS: The administration of a low dose of THC (0.3 mg/kg) produced clear
      anxiolytic-like responses in the light-dark box, as previously reported. The
      effects of the pretreatment with the CB(1) cannabinoid receptor antagonist, SR
      141716A (0.5 mg/kg), or the micro -opioid receptor antagonist, beta
      funaltrexamine (5 mg/kg), the delta-opioid receptor antagonist, naltrindole (2.5
      mg/kg) and the kappa-opioid receptor antagonist, nor-binaltorphimine (2.5 mg/kg)
      were evaluated on anxiolytic-like responses induced by THC. RESULTS: SR 141716A
      completely blocked the anxiolytic-like response induced by THC, suggesting that
      this effect is mediated by CB(1) cannabinoid receptors. The micro -opioid
      receptor antagonist beta-funaltrexamine and the delta-opioid receptor antagonist
      naltrindole, but not the kappa-opioid receptor antagonist nor-binaltorphimine,
      abolished THC anxiolytic-like effects, suggesting an involvement of micro - and
      delta-opioid receptors in this behavioural response. CONCLUSIONS: These results
      demonstrate that the endogenous opioid system is involved in the regulation of
      anxiety-like behaviour by cannabinoids and provide new findings to clarify
      further the interaction between these two neuronal systems.

PMID- 12185409
TI  - Acute citalopram administration produces correlated increases in plasma and
      salivary cortisol.
AB  - RATIONALE: Intravenous administration of the selective serotonin (5-HT) re-uptake
      inhibitor, citalopram, increases plasma cortisol. This would be expected to
      produce a parallel increase in salivary cortisol concentration. OBJECTIVE: To
      find out whether IV citalopram produces correlated increases in plasma and
      salivary cortisol levels. METHODS: Twelve healthy volunteers were tested on two
      occasions receiving either citalopram (10 mg IV) or saline in a double-blind,
      randomised, cross-over design. Plasma and salivary cortisol levels were measured
      before and for 150 min after each infusion. RESULTS: Relative to placebo,
      citalopram significantly increased cortisol levels in both plasma and saliva. The
      size of the increases in plasma and saliva cortisol correlated significantly with
      each other. CONCLUSIONS: Monitoring changes in salivary cortisol might be a valid
      and acceptable means of measuring 5-HT-mediated cortisol release.

PMID- 12185410
TI  - Lipoic acid in combination with a chelator ameliorates lead-induced peroxidative
      damages in rat kidney.
AB  - The deleterious effect of lead has been attributed to lead-induced oxidative
      stress with the consequence of lipid peroxidation. The present study was designed
      to investigate the combined effect of DL-alpha-lipoic acid (LA) and meso-2,3
      dimercaptosuccinic acid (DMSA) on lead-induced peroxidative damages in rat
      kidney. The increase in peroxidated lipids in lead-poisoned rats was accompanied
      by alterations in antioxidant defence systems. Lead acetate (Pb, 0.2%) was
      administered in drinking water for 5 weeks to induce lead toxicity. LA (25 mg/kg
      body weight per day i.p.) and DMSA (20 mg/kg body weight per day i.p.) were
      administered individually and also in combination during the sixth week.
      Nephrotoxic damage was evident from decreases in the activities of gamma-glutamyl
      transferase and N-acetyl beta- D-glucosaminidase, which were reversed upon
      combined treatment with LA and DMSA. Rats subjected to lead intoxication showed a
      decline in the thiol capacity of the cell, accompanied by high malondialdehyde
      levels along with lowered activities of catalase, superoxide dismutase,
      glutathione peroxidase and glutathione metabolizing enzymes (glutathione
      reductase, glucose-6-phosphate dehydrogenase, glutathione- S-transferase).
      Supplementation with LA as a sole agent showed considerable changes over
      oxidative stress parameters. The study has highlighted the combined effect of
      both drugs as being more effective in reversing oxidative damage by bringing
      about an improvement in the reductive status of the cell.

PMID- 12185411
TI  - Protective effect of Tiron (4,5-dihydroxybenzene-1,3-disulfonic acid disodium
      salt) against beryllium-induced maternal and fetal toxicity in rats.
AB  - The efficacy of Tiron (4,5-dihydroxybenzene 1,3-disulfonic acid disodium salt)
      was examined in the treatment of beryllium-induced maternal and developmental
      toxicity in rats. Single administration of beryllium nitrate at a dose of 50
      mg/kg (i.m.) on day 13 of gestation caused reductions in fetal and placental
      weights, the number of implantation sites and number of corpora lutea, as well as
      causing post-implantation loss, stunted growth, increase in the number of
      resorptions, and also a disturbed sex ratio. Maternal toxicity was demonstrated
      by reduction in body weight gain. Administration of beryllium also showed
      significant alteration in the hematological and biochemical indices of the mother
      as well as the fetus. Marked decreases were recorded in hemoglobin percentage,
      blood sugar levels, serum protein contents and serum alkaline phosphatase
      activity. By contrast, significant elevation was found in the activity of
      transaminases (aspartate aminotransferase and alanine aminotransferase). Tissue
      protein contents, glycogen contents, activities of alkaline phosphatase,
      adenosine triphosphatase and succinic dehydrogenase of kidney, lungs and uterus,
      and maternal and fetal liver all showed significantly decreased values after
      beryllium exposure, and remarkable elevation was observed in acid phosphatase,
      glucose-6-phosphatase and hepatic lipid peroxidation. These parameters were
      restored considerably with administration of 471 mg/kg i.m. Tiron from days 14 to
      18 of gestation. Atomic absorption spectrophotometry also revealed a high
      concentration of beryllium in different organs of pregnant rats. Interestingly, a
      small amount of metal ion was also detected in the fetus and reduced accumulation
      of beryllium was noticed after Tiron treatment.

PMID- 12185412
TI  - Lethal manganese-cadmium intoxication. A case report.
AB  - A case of a lethal manganese-cadmium (Mn-Cd) intoxication is reported. The
      postmortem examination revealed a noticeable reddish-violet discolouration of the
      serous cutes of all body cavities, but there was no indication of any corrosive
      burns of the mucous membranes of the gastrointestinal tract. An Mn concentration
      of 899 micro g/l blood and a Cd concentration of 238 micro g/l blood were found
      in the deceased woman. These concentrations are higher than normal levels by a
      factor of about 100. A subacute or chronic manganese-cadmium absorption must be
      assumed.

PMID- 12185413
TI  - Pharmacokinetic profile and placental transfer of a single intravenous injection
      of [(14)C]chlorpyrifos in pregnant rats.
AB  - The pharmacokinetics and placental transfer of a single intravenous dose of 5.0
      mg/kg (10 micro Ci/kg) ring-labeled [(14)C]chlorpyrifos were investigated in
      pregnant Sprague-Dawley rats at 11-13 days of gestation. Three rats were killed
      at 5, 15 or 30 min, or 1, 2, 4, 8, 12, 18, 24, 36, 48, 72 or 96 h after dosing.
      Radioactivity and 3,5,6-trichloropyridinol (TCP) were detected in all tissues 5
      min after dosing. Chlorpyrifos was only found in maternal plasma and liver. Peak
      maternal plasma concentration of radioactivity ( micro g chlorpyrifos
      equivalents/ml) was 157 at 5 min, compared with 1.9 for fetal plasma at 15 min.
      The maximum concentrations of radioactivity ( micro g chlorpyrifos
      equivalents/g), detected in most tissues within 12 h of dosing, were, in
      descending order: liver (30), brain (29), placenta (21), and fetus (2). All peaks
      occurred at 5 min except for fetus and fetal plasma, which were at 15 min. TCP
      was detected by HPLC as the major compound identified in plasma and tissues. The
      maximum concentration detected was in plasma, at 12.4 micro g/ml, and for the
      following tissues was: liver 4.3 ng/g fresh tissue, fetus 4 ng/g, placenta 2.97
      ng/g, brain 1.68 ng/g, and fetal plasma 0.52 ng/g. All TCP peaks occurred at 5
      min except for fetus at 30 min and fetal plasma at 15 min. Parent chlorpyrifos
      was detected in maternal plasma and liver at maximum concentrations of 5.1 micro
      g/ml and 0.40 micro g/g, respectively, at 5 min. Chlorpyrifos was detectable in
      maternal plasma up to 36 h after dosing, and in liver up to 24 h after dosing.
      Pharmacokinetic analysis best described radioactivity, chlorpyrifos, and TCP as
      disappearing biexponentially from plasma and tissues. The terminal elimination
      half-lives of radioactivity, chlorpyrifos and TCP from maternal plasma were 16,
      18, and 16 h, respectively. The results indicate that (1). chlorpyrifos undergoes
      a rapid metabolism to its major metabolites (TCP); (2). chlorpyrifos and its
      metabolites are distributed to all maternal and fetal tissues and plasma; and
      (3). the elimination of chlorpyrifos and TCP is slow, with redistribution from
      lipid stores a likely determinant of elimination rates.

PMID- 12185414
TI  - Target cells for cytochrome p450-catalysed irreversible binding of 7,12
      dimethylbenz[a]anthracene (DMBA) in rodent adrenal glands.
AB  - 7,12-Dimethylbenz[a]anthracene (DMBA) is an adrenocorticolytic agent that causes
      apoplexy (haemorrhage) and massive necrosis in the adrenal cortex in rat. Several
      explanations regarding the origin of toxicity have been proposed. Huggins and
      Morii (J Exp Med 114:741-60, 1961) suggested that the cells of the inner adrenal
      cortex are the primary target, whereas Horvath and Kovacs (Pathol Eur 8:43-59,
      1973) suggested the vascular endothelium as being the origin of toxicity. In the
      present study, cultured precision-cut tissue slices were used to localize target
      cells for irreversible [(3)H]DMBA binding in rat and mouse adrenal cortex. The
      sites of binding were confirmed by autoradiography in vivo. Irreversible
      [(3)H]DMBA binding was confined to zona fasciculata/reticularis cells in rat (but
      not in mouse) adrenal cortex. Pronounced binding was observed in clusters of
      cells (focal binding), localized predominantly in zona reticularis of rat.
      [(3)H]DMBA binding in zona fasciculata/reticularis cells was inhibited by the
      cytochrome p450 1A/B (CYP1A/B) inhibitors ellipticine, alpha-naphthoflavone, and
      1-ethynylpyrene. The CYP11B1-inhibitor metyrapone did not reduce [(3)H]DMBA
      binding. In CYP1-induced (PCB 126-treated) rats and mice, intense irreversible
      [(3)H]DMBA binding was found also in endothelial cells of the adrenal cortex. The
      endothelial binding was abolished by the CYP1 inhibitors but remained unaffected
      by metyrapone. We conclude that the metabolic activation in adrenal parenchymal
      cells is presumably catalysed by CYP1B1, whereas CYP1A1 presumably catalyses the
      activation in endothelial cells. We suggest that the adrenocorticolytic effect of
      DMBA is the result of a dual mode of action, targeting both endothelial and
      parenchymal cells in the rat adrenal cortex.

PMID- 12185415
TI  - No relationship exists between itai-itai disease and TA repeat polymorphisms of
      the estrogen receptor alpha gene.
AB  - Itai-itai (ouch-ouch) disease is a syndrome accompanied by bone mineral disorders
      that may be related to oral cadmium exposure. Itai-itai predominantly affects
      postmenopausal women with a history of multiple childbirth. In a previous study
      we have examined the genotype distributions of PvuII and XbaI restriction
      fragment length polymorphisms of the estrogen receptor alpha (ER alpha) gene in
      patients with itai-itai disease and compared them with those of controls.
      However, no significant differences were shown between the genotype distributions
      of the patients and controls. In the present study, we determined the TA repeat
      polymorphisms of the patients and controls. The distributions of the patients
      were: HH 25.0%, HL 50.0%, and LL 25.0%; where HH includes two alleles with a high
      number of TA repeats (TA> or =16), HL includes one high number allele and one low
      number allele (TA< or =15), and LL includes two alleles with a low number of TA
      repeats. These patients' distributions were not significantly different from
      those of the controls. Although our sample number was limited, we concluded that
      a polymorphism variant of the ER alpha gene is not a predisposing factor for itai
      itai disease.

PMID- 12185416
TI  - The effects of methidathion on lipid peroxidation and some liver enzymes: role of
      vitamins E and C.
AB  - Methidathion (MD) [ O, O-dimethyl S-(2,3-dihydro-5-methoxy-2-oxo-1,3,4-thiadiazol
      3-ylmethyl) phosphorodithioate] is one of the most widely used organophosphate
      insecticides (OPIs) in agriculture and public health programmes. We have,
      therefore, examined the in vivo and in vitro effects of MD on the serum
      activities of cholinesterase (ChE), enzymes concerning liver damage and lipid
      peroxidation (LPO; only in vivo), and have evaluated the ameliorating effects of
      a combination of vitamins E and C against MD toxicity. The in vivo experimental
      groups were: control group, MD-treated group (MD), and a group treated with MD
      plus vitamin E plus vitamin C (MD+Vit). The MD and MD+Vit groups were treated
      orally with a single dose of 8 mg MD/kg body weight at 0 h. Vitamin E and vitamin
      C were injected at doses of 150 mg/kg body weight i.m. and 200 mg/kg body weight
      i.p., respectively, 30 min after the treatment with MD in the MD+Vit group. Blood
      samples were taken 24 h after the MD administration. For in vitro study, venous
      blood samples were obtained from volunteers, and serum recovered. The activities
      of serum enzymes were determined in each sample and these served as 0 h values.
      Each sample was divided into four portions, each of which served as one of the
      experimental groups, as follows: control group, vitamin E plus vitamin C group
      (Vit), MD-treated group (MD) and MD plus vitamin E plus vitamin C group (MD+Vit).
      Vitamin E and vitamin C were added at doses of 7.5 and 10 micro g/ml,
      respectively, into the Vit and MD+Vit groups. MD was added at doses of 0.4 mg/ml
      into the MD and MD+Vit groups. The activities of serum enzymes were determined in
      each sample at 24 h. The results of the in vivo experiment demonstrated that
      thiobarbituric acid reactive substances were increased in the MD group compared
      with the control group, and decreased in the MD+Vit group compared with MD group.
      ChE activity was decreased in both MD and MD+Vit groups compared with controls
      and increased in the MD+Vit group compared with the MD group. The activities of
      aspartate aminotransferase (AST), alkaline phosphatase (ALP), gamma
      glutamyltransferase (GGT) and lactate dehydrogenase (LDH) were increased in both
      the MD and MD+Vit groups compared with the control group. AST activity was
      decreased in MD+Vit group compared with the MD group. Alanine aminotransferase
      (ALT) activity was decreased in both the MD and MD+Vit groups compared with
      control group. The results of in vitro experiment showed that all enzyme
      activities remained unchanged in both the control and Vit groups compared with
      values at 0 h. The activities of ChE, ALT and LDH were decreased in both the MD
      and MD+Vit groups compared with 0 h values. There was no significant difference
      between the MD and MD+Vit groups. The activities of AST, ALP and GGT remained
      unchanged in all groups. From these results, it can be concluded that MD caused
      liver damage, and LPO may be one of the molecular mechanisms involved in MD
      induced toxicity. Single-dose treatment with a combination of vitamins E and C
      after the administration of MD can reduce LPO caused by MD.

PMID- 12185417
TI  - Behavioural changes related to olfactory mucosal metaplasia and bulbar glial
      fibrillary acidic protein (GFAP) induction in methylsulphonyl-dichlorobenzene
      treated mice.
AB  - Methylsulphonyl-2,6-dichlorobenzene [2,6-(diCl-MeSO(2)-B)], and its 2,5
      chlorinated isomer [2,5-(diCl-MeSO(2)-B)] bind firmly in the olfactory mucosa of
      mice. Both isomers are also selectively localised in the olfactory bulb.
      Persistent olfactory mucosal metaplasia is induced by 2,6-(diCl-MeSO(2)-B)
      whereas 2,5-(diCl-MeSO(2)-B) has no effects. Furthermore, a strong induction of
      glial fibrillary acidic protein (GFAP) restricted to the olfactory bulb has been
      reported in 2,6-(diCl-MeSO(2)-B)-treated mice. To explore whether these lesions
      give rise to early or long-lasting changes in behaviour, spontaneous motor
      activity and radial arm maze (RAM) learning were examined at 1, 2, 4 and 12 weeks
      following an intraperitoneal injection of a single low (32 mg/kg) or high (65
      mg/kg) dose of 2,6-(diCl-MeSO(2)-B). 2,5-(DiCl-MeSO(2)-B) (65 mg/kg) was used as
      a negative control. Hyperactivity was observed in all treatment groups while
      deficits in the RAM performance was only seen in the 2,6-(diCl-MeSO(2)-B)-treated
      groups. Alterations in motor activity and impaired performance in the RAM-test
      induced by 2,6-(diCl-MeSO(2)-B) persisted up to 2 weeks in the low-dose group and
      12 weeks in the high-dose group. The low-dose group consistently showed a less
      pronounced effect than the high-dose group. The 2,5-(diCl-MeSO(2)-B)-induced
      changes in motor activity declined rapidly and did not remain after 2 weeks. As
      determined by immunohistochemistry, 2,6-(diCl-MeSO(2)-B)-induced GFAP
      immunoreactivity was mainly confined to the glomerular layer of the olfactory
      bulb. We propose that the behavioural deficits caused by 2,6-(diCl-MeSO(2)-B)
      result from a primary loss of sensory neurons in the olfactory mucosa with
      consequent astrocyte proliferation in the glomerular layer of the olfactory bulb.
      A targeted uptake of metabolites into the olfactory bulb could also contribute to
      the GFAP induction and/or behaviour response.

PMID- 12185418
TI  - Lipid peroxidation and cell death mechanisms in pulmonary epithelial cells
      induced by peroxynitrite and nitric oxide.
AB  - Nitric oxide (NO) is an environmental pollutant found in smog and cigarette
      smoke. Recently, NO has been discovered to act as a molecular messenger,
      mediating various physiological functions. However, when an excess of NO is
      present, cytotoxic and mutagenic effects can also be induced. The reaction of NO
      with superoxide results in the formation of peroxynitrite (ONOO(-)), which
      decomposes into the hydroxyl radical and nitrogen dioxide. Both of them are
      potent oxidant species that may initiate and propagate lipid peroxidation. In the
      present study, we examined the effects of NO and ONOO(-) on the induction of
      lipid peroxidation and cell death mechanisms in rats and in A549 pulmonary
      epithelial cells. The results showed that ONOO(-) is able to induce lipid
      peroxidation in pulmonary epithelial cells in a dose-dependent manner. 8-Epi
      prostaglandin F(2)(alpha) can serve as a good biomarker of lipid peroxidation
      both in vitro and in vivo. Postmitotic apoptosis was found in A549 cells exposed
      to NO, whereas ONOO(-) induced cell death more characteristic of necrosis than
      apoptosis. Apoptosis that occurred in cells may be related to the dysfunction of
      mitochondria, the release of cytochrome c into cytosol, and the activation of
      caspase-9. The relationship between caspase activation and the cleavage of other
      death substrates during postmitotic apoptosis in A549 cells needs further
      investigation.

PMID- 12185419
TI  - Pulmonary and cardiac sequelae of subarachnoid haemorrhage: time for active
      management?
AB  - Cardiac injury and pulmonary oedema occurring after acute neurological injury
      have been recognised for more than a century. Catecholamines, released in massive
      quantities due to hypothalamic stress from subarachnoid haemorrhage (SAH), result
      in specific myocardial lesions and hydrostatic pressure injury to the pulmonary
      capillaries causing neurogenic pulmonary oedema (NPO). The acute, reversible
      cardiac injury ranges from hypokinesis with a normal cardiac index, to low output
      cardiac failure. Some patients exhibit both catastrophic cardiac failure and NPO,
      while others exhibit signs of either one or other, or have subclinical evidence
      of the same. Hypoxia and hypotension are two of the most important insults which
      influence outcome after acute brain injury. However, despite this, little
      attention has hitherto been devoted to prevention and reversal of these
      potentially catastrophic medical complications which occur in patients with SAH.
      It is not clear which patients with SAH will develop important cardiac and
      respiratory complications. An active approach to investigation and organ support
      could provide a window of opportunity to intervene before significant hypoxia and
      hypotension develop, potentially reducing adverse consequences for the long-term
      neurological status of the patient. Indeed, there is an argument for all SAH
      patients to have echocardiography and continuous monitoring of respiratory rate,
      pulse oximetry, blood pressure and electrocardiogram. In the event of cardio
      respiratory compromise developing i.e. cardiogenic shock and/or NPO, full
      investigation, attentive monitoring and appropriate intervention are required
      immediately to optimise cardiorespiratory function and allow subsequent
      definitive management of the SAH.

PMID- 12185420
TI  - Future directions in the management of tertiary peritonitis.

PMID- 12185422
TI  - Risk factors of failure and immediate complication of subclavian vein
      catheterization in critically ill patients.
AB  - OBJECTIVE: To identify the risk factors of failure and immediate complication of
      subclavian vein catheterization (SVC). DESIGN: Prospective observational study.
      SETTING: Surgical critical care unit of a tertiary university hospital. PATIENTS:
      Critically ill patients requiring a first SVC. INTERVENTION: Subclavian vein
      catheterization was attempted in 707 patients without histories of surgery or
      radiotherapy in the subclavian area. Failed catheterizations, arterial punctures,
      pneumothoraces and misplacements of the catheter tip were recorded. Risk factors
      of failure and immediate complication were isolated among patients'
      characteristics, procedure parameters (side and number of venipunctures) and the
      operator's experience using a univariate +/- multivariate analysis. MEASUREMENTS
      AND MAIN RESULTS: Five hundred sixty-two SVCs (79.5%) were achieved without
      adverse events. Among the remaining 145 catheterizations, 67 (9.5%) failures, 55
      (7.8%) arterial punctures, 22 (3.1%) pneumothoraces and 30 (4.2%) misplacements
      of the catheter tip occurred. More than one venipuncture was the only risk factor
      of failed catheterization [2 venipunctures, odds ratio =7.4 (2.1-26); >2
      venipunctures, odds ratio =49.1 (16.8-144.1)]. More than one venipuncture and age
      77 years or more were predictive of the occurrence of immediate complications [2
      venipunctures, odds ratio =3.6 (1.8-7.0); >2 venipunctures, odds ratio =14 (7.7
      25.3); age >or=77, odds ratio =1.8 (1.0-3.1)]. The operator's training was not
      predictive of failed catheterization or immediate complication. CONCLUSION: For
      SVC, more than one venipuncture is predictive of failed catheterization and
      immediate complication. Age 77 years or more was predictive of immediate
      complications.

PMID- 12185421
TI  - Associations between empirical antimicrobial therapy at the hospital and
      mortality in patients with severe community-acquired pneumonia.
AB  - INTRODUCTION: The aim of the study was to examine different antibiotic choices
      and their relation to outcomes. METHODS: We reviewed patients with severe
      community-acquired pneumonia (SCAP) from two multicenter studies. Empirical
      antimicrobial regimens were classified as: macrolides alone (group M); macrolides
      plus betalactams (group MB); macrolides plus betalactam/betalactamase inhibitor
      (group MBI); every regimen including aminoglycosides (group A); non-pseudomonal
      third-generation cephalosporins alone (group C); another betalactam alone (first-
      and second-generation cephalosporins, or betalactam/betalactamase inhibitor)
      (group B); fluoroquinolones (group F); and other regimens (group Misc). RESULTS:
      Initial distribution of regimens was: group MB: 261 patients; group A: 65
      patients; group C: 31 patients; group B: 23 patients; group M: 18 patients; group
      MBI: 13 patients; group F: 11 patients; group Misc: 38 patients. The lowest
      overall mortality was associated with initial treatment with a macrolide plus
      other agent (or alone). No deaths were documented among the 13 patients receiving
      amoxicillin/clavulanate plus a macrolide. The excess mortality for initial
      treatment with group A was significantly higher (14.2%; CI 95% 27.3-1.1) than the
      overall mortality rate between patients receiving a macrolide plus other agents.
      No significant differences were documented when mortality was adjusted for
      intubated patients. CONCLUSION: Clinicians select the empirical antibiotic
      regimen after classifying patients according to likely pathogens and prognosis.
      The inclusion of a macrolide as part of the initial therapeutic regimen for SCAP
      appears to be as safe and effective as alternative options. Addition of a
      macrolide agent to a betalactam/betalactamase inhibitor or using a macrolide
      alone was a marker for less severe disease.

PMID- 12185423
TI  - Dead-space reduction and tracheal pressure measurements using a coaxial inner
      tube in an endotracheal tube.
AB  - OBJECTIVE: To evaluate the effects on CO(2) washout of the coaxial double lumen
      tube (DLT) as compared to a standard endotracheal tube (ETT) and tracheal gas
      insufflation (TGI). Precision of tracheal pressure monitoring through the DLT and
      safety issues, including intrinsic PEEP (PEEPi) formation during DLT ventilation,
      were also evaluated. DESIGN: Lung model study. SETTING: University research
      laboratory. MEASUREMENTS AND RESULTS: CO(2) washout was analysed in a lung model
      by measuring single alveolar CO(2) concentration during DLT ventilation as
      compared to standard ETT ventilation, at different minute ventilation (6-14
      l/min) and different CO(2)-output levels (180 ml/min, 240 ml/min, and 300
      ml/min). At a CO(2) output level of 240 ml/min the CO(2) washout was also
      compared to tidal volume-adjusted continuous TGI and expiratory synchronised TGI.
      Precision of tracheal pressure monitoring and PEEPi formation during DLT
      ventilation was evaluated by comparing pressure in each limb above the tube to
      reference tracheal pressure, varying I:E ratios (1:2, 1:1, and 2:1), tidal
      volumes (300-700 ml), breathing frequencies (15-25), and compliance (20-50
      ml/cmH(2)O). DLT ventilation had the same efficacy in removing CO(2) as
      continuous and expiratory synchronised TGI, reducing single alveolar CO(2)
      concentration by 9-21% compared to normal ventilation. Tracheal pressure could be
      measured through the DLT with high precision. There was only marginal formation
      of PEEPi at tidal volumes <or=600 ml, I:E ratio <or=1:1, and compliance <or=35
      ml/cmH(2)O. CONCLUSIONS: The double lumen tube is as effective as tracheal gas
      insufflation in reducing CO(2) tension. Tracheal pressure and formation of PEEPi
      can be monitored with high precision without interrupting ventilation.

PMID- 12185424
TI  - Bench testing of pressure support ventilation with three different generations of
      ventilators.
AB  - OBJECTIVE: The new generations of intensive care ventilators tend to be more
      innovative and sophisticated than previous ones, but little is known about their
      respective performance for delivering pressure support ventilation (PSV) and how
      they compare to previous generations. DESIGN: Active lung model bench test.
      APPARATUS: Twenty-two commercially available ventilators classified into three
      categories: new generation ventilators (after 1993, n=7), previous generation
      (before 1993, n=6), and recent piston or turbine-based ventilators ( n=9).
      MEASUREMENTS AND RESULTS: During PSV, the unloading efficacy of the assistance
      depends on the ventilator's ability to meet inspiratory flow demand. Three levels
      of flow (0.1 l/s, 0.6 l/s, and 1.2 l/s) were used to simulate inspiratory demand
      and the net area of the inspiratory airway pressure-time trace was calculated
      over the first 0.3 s, 0.5 s, and 1 s (Area (0.3), Area (0.5), and Area (tot))
      with three levels of PSV (5 cmH(2)O, 10 cmH(2)O, and 15 cmH(2)O). To assess the
      respective role of pressure support delivery and triggering function, triggering
      sensitivity was assessed independently by measuring the time delay ( TD (tg)) and
      the pressure fall (Delta Paw (tg)) with two levels of inspiratory drive. All the
      new generation ventilators exhibited significantly better results than most of
      the previous generation ventilators regarding Area (0.3) and TD (tg), indicating
      large improvements in terms of triggering and pressurisation. CONCLUSION:
      Regarding PSV and trigger performance, the new generation ventilators - but also
      some piston and turbine-based ventilators - outperform most of previous
      generation ventilators.

PMID- 12185425
TI  - Protocol-directed weaning from mechanical ventilation: clinical outcome in
      patients randomized for a 30-min or 120-min trial with pressure support
      ventilation.
AB  - OBJECTIVE: To investigate the possibility of successful extubation performing a
      spontaneous breathing trial (SBT) in pressure support ventilation (PSV) with
      target durations of 30 and 120 min. DESIGN AND SETTING: Prospective and
      randomized study in two medical-surgical adult intensive care units. PATIENTS AND
      PARTICIPANTS: 98 adult patients supported by mechanical ventilation for at least
      48 h and considered ready for a weaning trial. INTERVENTIONS: An SBT conducted in
      PSV with 7 cmH(2)O and patients randomly assigned to two groups with target
      durations of 30- and 120-min. MEASUREMENTS AND RESULTS: In the 30-min group 43
      patients (93%) tolerated the SBT and were extubated while 4 (9%) needed
      reintubation within 48 h; in the 120-min group 46 patients (88%) successfully
      completed the trial and were extubated while 2 (4%) were reintubated. ICU
      mortality in the groups with short and long periods was 6% and 4%, and in
      hospital mortality 20% and 17%, respectively. Those successful in the 30- and 120
      min groups had similar length of ICU stay (6 and 7 days, respectively) and in
      hospital length of stay (20 and 25 days, respectively). Compared to the
      successfully extubated, the reintubated patients had significantly higher length
      of ICU stay and mortality (17 vs. 6 days and 33 vs. 3.6%, respectively).
      CONCLUSIONS: An SBT with PSV of 7 cmH(2)O lasting 30 min is equally effective in
      recognizing the successfully extubated patients as a 120-min trial.

PMID- 12185426
TI  - Nitric oxide contamination of hospital compressed air improves gas exchange in
      patients with acute lung injury.
AB  - OBJECTIVE: We tested the hypothesis that NO contamination of hospital compressed
      air also improves PaO(2) in patients with acute lung injury (ALI) and following
      lung transplant (LTx). DESIGN: Prospective clinical study. SETTING:
      Cardiothoracic intensive care unit. PATIENTS: Subjects following cardiac surgery
      (CABG, n=7); with ALI (n=7), and following LTx (n=5). INTERVENTIONS: Four
      sequential 15-min steps at a constant FiO(2) were used: hospital compressed air
      O(2) (H1), N(2)-O(2) (A1), repeat compressed air-O(2) (H2), and repeat N(2)-O(2)
      (A2). MEASUREMENTS AND RESULTS: NO levels were measured from the endotracheal
      tube. Cardiorespiratory values included PaO(2) were measured at the end of each
      step. FiO(2) was 0.46+/-0.05, 0.53+/-0.15, and 0.47+/-0.06 (mean+/-SD) for three
      groups, respectively. Inhaled NO levels during H1 varied among subjects (30-550
      ppb, 27-300 ppb, and 5-220 ppb, respectively). Exhaled NO levels were not
      detected in 4/7 of CABG (0-300 ppb), 3/6 of ALI (0-140 ppb), and 3/5 of LTx (0-59
      ppb) patients during H1, whereas during A1 all but one patient in ALI and three
      CABG patients had measurable exhaled NO levels (P<0.05). Small but significant
      decreases in PaO(2) occurred for all groups from H1 to A1 and H2 to A2 (132-99
      Torr and 128-120 Torr, P <0.01, respectively). There was no correlation between
      inhaled NO during H1 and exhaled NO during A1 or the change in PaO(2) from H1 to
      A1. CONCLUSIONS: Low-level NO contamination improves PaO(2) in patients with ALI
      and following LTx.

PMID- 12185427
TI  - High values of the pulmonary artery wedge pressure in patients with acute lung
      injury and acute respiratory distress syndrome.
AB  - OBJECTIVE: To determine the incidence and severity of pulmonary artery wedge
      pressure (PAWP) elevation in patients with ALI/ARDS. In addition, to examine the
      effects of clinical variables on the presence of a high PAWP (>18 mmHg) and the
      effect of an elevated PAWP on mortality. DESIGN AND PATIENTS: Post hoc analysis
      of 120 patients with or at high risk of ARDS, enrolled in a randomized controlled
      trial of pressure- and volume-limited ventilation. Patients with or at high risk
      of congestive heart failure were excluded from the original study. SETTING: Eight
      tertiary intensive care units. MEASUREMENTS AND RESULTS: Pulmonary artery
      catheters were inserted at the discretion of the attending physician, and PAWP
      was collected every 8 h when present. Of 120 subjects 71 (59%) had a pulmonary
      artery catheter (44 at randomization, 27 later). The mean maximum PAWP reading
      among patients was 22.5 mmHg (95% CI 21.2-23.8) and mean median was 16.6 mmHg
      (95% CI 15.6-17.5). Patients who met standard criteria for ARDS were more likely
      to develop a high PAWP. In a multivariate stepwise logistic regression model a
      persistently elevated PAWP (median >18 mmHg) was a strong predictor of mortality
      after correction for baseline differences (OR estimate 6.82; 95% CI 1.66-37.81).
      CONCLUSIONS: We conclude that in this group of patients a PAWP higher than 18
      mmHg is common. Mandating a PAWP of 18 mmHg or less may negatively impact
      clinical trials in which ARDS is an inclusion/exclusion criteria or an endpoint.

PMID- 12185428
TI  - Influence of respiratory rate on gas trapping during low volume ventilation of
      patients with acute lung injury.
AB  - OBJECTIVE: Reduction in tidal volume (Vt) associated with increase in respiratory
      rate to limit hypercapnia is now proposed in patients with acute lung injury
      (ALI). The aim of this study was to test whether a high respiratory rate induces
      significant intrinsic positive end-expiratory pressure (PEEPi) in these patients.
      DESIGN: Prospective crossover study. SETTING: A medical intensive care unit.
      INTERVENTIONS AND MEASUREMENTS: Ten consecutive patients fulfilling criteria for
      severe ALI were ventilated with a 6 ml/kg Vt, a total PEEP level at 13+/-3
      cmH(2)O and a plateau pressure kept at 23+/-4 cmH(2)O. The respiratory rate was
      randomly set below 20 breaths/min (17+/-3 breaths/min) and increased to 30
      breaths/min (30+/-3 breaths/min) to compensate for hypercapnia. External PEEP was
      adjusted to keep the total PEEP and the plateau pressure constant. PEEPi was
      computed as the difference between total PEEP and external PEEP. The lung volume
      retained by PEEPi was then measured. RESULTS: Increase in respiratory rate
      resulted in significantly higher PEEPi (1.3+/-0.4 versus 3.9+/-1.1 cmH(2)O,
      p<0.01) and trapped volume (70+/-43 versus 244+/-127 ml, p<0.01). External PEEP
      needed to be reduced from 11.9+/-3.4 to 9.7+/-2.9 cmH(2)O ( p<0.01). PaO(2) was
      not affected but the alveolar-arterial oxygen tension difference slightly
      worsened with the high respiratory rate (p<0.05). CONCLUSIONS: An increase in
      respiratory rate used to avoid Vt reduction-induced hypercapnia may induce
      substantial gas trapping and PEEPi in patients with ALI.

PMID- 12185429
TI  - Left ventricular dysfunction in lethal severe brain injury: impact of
      transesophageal echocardiography on patient management.
AB  - OBJECTIVE: To evaluate the impact of transesophageal echocardiographic (TEE)
      studies on further patient management and incidence and degree of left
      ventricular (LV) dysfunction in patients with lethal severe brain injury. DESIGN
      AND SETTING: Retrospective, clinical study in two surgical intensive care units
      in a university hospital. PATIENTS: In 51 patients with severe brain injury
      ultimately leading to brain death, the results of TEE studies were reviewed for
      evidence of newly developed LV dysfunction (i.e., regional wall motion
      abnormalities) and its impact on patient management. MEASUREMENTS AND RESULTS:
      Seven patients (13.7%) had a diminished LV function global (fractional area
      change <50%). Four of these patients (7.8%) exhibited a severely reduced LV
      function (fractional area change <35%). Regional wall motion abnormalities and
      preserved global function were found in eight patients (15.7%). Patient
      management was altered in all patients with diminished LV function:
      implementation of advanced hemodynamic monitoring (n=5), institution or
      adjustment of inotropes and adjustment of fluid management (n=7). In patients
      exhibiting a severely reduced LV function and deteriorating cardiovascular
      status, brain death diagnosis was established by one clinical examination in
      conjunction with laboratory tests, thus shortening the interval required for
      brain death diagnosis by about 12 h. CONCLUSIONS: Severe LV dysfunction occurred
      in about 8% of our patients with severe brain injury ultimately leading to brain
      death. TEE may be helpful in guiding cardiovascular resuscitation ultimately
      leading to improved organ procurement rates.

PMID- 12185430
TI  - Influence of inspiration:expiration ratio on intracranial and cerebral perfusion
      pressure in acute stroke patients.
AB  - OBJECTIVE: We undertook this study to evaluate the influence of the
      inspiration:expiration (I:E) ratio on intracranial pressure and cerebral
      perfusion in patients with acute stroke. DESIGN: Ventilated patients with acute
      stroke were examined under a protocol involving variations of I:E ratio from 1:2
      to 1:1 to 1:2 under positive end-expiratory pressure (PEEP) of 5.3 and -
      subsequently - 10.6 cmH(2)O. Intracranial pressure was monitored with parenchymal
      or ventricular catheters. Mean arterial blood pressure, intracranial pressure
      (ICP), heart rate and peak mean flow velocity of the middle cerebral arteries
      were continuously recorded. SETTING: Neurological intensive care unit. PATIENTS:
      A total of 45 monitoring sessions were performed in 16 patients (subarachnoid
      haemorrhage 3, ischemic stroke 13). RESULTS: No significant changes in any of the
      parameters monitored were evident in association with the I:E ratio variations
      under either of the PEEP levels applied. It must be noted, though, that ICP
      exceeded 15 mmHg in only 5/45 monitoring sessions, and never exceeded 20 mmHg.
      CONCLUSIONS: Our preliminary results suggest that variations of the I:E ratio
      cause no significant changes in intracranial or cerebral perfusion pressure and,
      thus, can be safely used in patients with acute stroke without intracranial
      hypertension. The influence of I:E ratio variations on stroke patients with
      intracranial hypertension remains to be evaluated.

PMID- 12185431
TI  - Early increase of procalcitonin after cardiovascular surgery in patients with
      postoperative complications.
AB  - OBJECTIVE: Type and frequency of postoperative abnormalities were registered
      after cardiovascular surgery to evaluate the aetiology and diagnostic value of
      increased concentrations of procalcitonin (PCT) and C-reactive protein (CRP)
      during the early postoperative period. DESIGN: Prospective, observational study.
      PATIENTS: Two hundred and eight patients undergoing coronary artery bypass
      grafting or valve replacement requiring cardiopulmonary bypass were monitored for
      7 days postoperatively for various types of infectious or non-infectious
      complications. Plasma PCT and CRP levels were measured on day 1 and day 2 after
      surgery and, when increased, until day 7. RESULTS: More patients with PCT above 2
      ng/ml on day 1 or 2 (n=55) had postoperative abnormalities (95%) than patients
      with lower PCT (59%). Specifically, the incidence of three or more criteria of
      the "systemic inflammatory response syndrome" was 45% versus 4% (area under the
      curve of the receiver operating characteristic 0.866); positive inotropic support
      was needed in 65% versus 9% (0.870); respiratory insufficiency
      (PaO(2)/FIO(2)<200) 38% versus 12% (0.704); proven and suspected bacterial
      infection 9% versus 1% (0.900) and 24% versus 1% (0.897), respectively. For CRP,
      the respective areas under the curve were all below 0.63, while all patients had
      elevated CRP levels, whether they had a complication or not. CONCLUSIONS:
      Elevated PCT, but not CRP, correlates with evidence of systemic inflammation and
      other complications early postoperatively after cardiac surgery. Although the PCT
      levels do not rise as quickly as the criteria of the systemic inflammatory
      response syndrome appear, they do reflect systemic inflammation. Early
      identification and quantification of a systemic inflammatory response may help
      reduce postoperative complications.

PMID- 12185432
TI  - An increase in urinary nitrite/nitrate excretion is associated with the
      hyperdynamic state after cardiovascular surgery.
AB  - OBJECTIVES: To test the hypotheses (1) that nitric oxide (NO) production is
      stimulated after cardiovascular surgery and is related to the hyperdynamic state
      and (2) that NO production is more prominent in patients with cardiopulmonary
      bypass. DESIGN: Prospective, clinical study. SETTING: Intensive care unit in a
      university hospital. PATIENTS: One hundred patients after cardiovascular surgery:
      coronary artery bypass graft with (n=53) and without (n=17) cardiopulmonary
      bypass, valve surgery with cardiopulmonary bypass (n=23) and thoracic aortic
      replacement with cardiopulmonary bypass (n=7). INTERVENTIONS: None. MEASUREMENTS
      AND RESULTS: Urinary nitrite/nitrate (NOx) excretion was measured by the high
      performance liquid chromatography-Griess system as an index of endogenous NO
      production during the first 2 postoperative days. Hemodynamic variables,
      hematologic variables and serum C-reactive protein concentrations were measured
      after the operation. Urinary NOx concentrations were 146+/-70 and 190+/-93 micro
      mol/l, and the amounts of NOx excreted in the urine were 23+/-10 and 18+/-8 micro
      mol/h on the 1st and 2nd days, respectively. Urinary NOx excretions were
      positively correlated with the cardiac index (P<0.01), but inversely correlated
      with the systemic vascular resistance index (P<0.01). Urinary NOx concentrations
      were positively correlated with serum C-reactive protein concentrations (P<0.01),
      but inversely correlated with the cardiopulmonary bypass time (P<0.01). The
      urinary NOx concentration was highest in patients undergoing coronary artery
      bypass graft without cardiopulmonary bypass. CONCLUSION: These findings suggest,
      firstly, that NO production is stimulated by a surgical inflammatory response
      and, secondly, that the endogenous NO contributes to the increase in cardiac
      output that accompanies the reduced systemic vascular resistance after
      cardiovascular surgery.

PMID- 12185433
TI  - Changes in intensive care from 1987 to 1997 - has outcome improved? A single
      centre study.
AB  - OBJECTIVES: To study changes in a single intensive care unit (ICU) over a 10 year
      period and to investigate possible concomitant changes in outcome. SETTING: The
      ICU populations in 1987 and 1997 in a university hospital. DESIGN AND METHODS:
      Prospective and retrospective cohort study. The ICU database was used for
      comparison of the ICU populations, and SAPS II-estimated hospital survival was
      compared with observed survival. Three year follow-up survival (the Peoples
      Registry) was compared with population survival (Statistics Norway). In the year
      2000 the Short Form 36 (SF 36) questionnaire was used for quality of life (QOL)
      measurement. Results were compared with a reference population. INTERVENTIONS:
      None. RESULTS: From 1987 to 1997 the numbers of patients and stays increased from
      219 and 236 to 338 and 370. ICU activity per stay increased considerably, but
      length of stay remained unchanged (6.0 versus 5.9 days). The 1997 ICU patients
      were, on average, older (50.3 versus 46.0 years) and more severely ill (SAPS II
      42.7 versus 34.7). They had a higher crude mortality, but the time from admission
      to when the observed mortality reached the predicted mortality was longer,
      indicating an increased survival length. Two years after intensive care, there
      was no excess mortality compared with population survival in either cohort. QOL
      was significantly reduced in both cohorts compared to population scores.
      CONCLUSIONS: This study indicates that the increased intensive care activity over
      the 10 year period was associated with a prolonged severity-adjusted survival.
      QOL was still reduced 3 and 13 years after ICU, compared to population scores.

PMID- 12185434
TI  - Effect of the degree of tricuspid regurgitation on cardiac output measurements by
      thermodilution.
AB  - OBJECTIVE: To determine the relationship between the degree of tricuspid
      regurgitation (TR) and accuracy of cardiac output measurement by thermodilution
      in mechanically ventilated patients. DESIGN AND SETTING. Prospective
      observational study in a 20-bed general intensive care unit in the university
      hospital. PATIENTS: We examined 27 patients (not undergoing cardiac surgery): 8
      with no or 1st degree TR, 9 with 2nd degree, and 10 with 3rd degree TR.
      INTERVENTIONS: All patients were measured twice using simultaneously
      transesophageal echocardiography and pulmonary artery catheter for cardiac
      output. MEASUREMENTS AND RESULTS: Continuous Doppler measurements were taken in
      the left ventricular outflow tract at the level of the aortic valve. Cardiac
      output was calculated by multiplying the velocity-time integral by aortic valve
      area and heart rate. Simultaneous pulmonary artery catheter measurements were
      taken averaging the results of the three 10-cc boluses of iced saline. The
      difference between the methods was 0.5+/-1.1 l/min (mean +/-2 SD) in patients
      with no or 1st degree TR (r=0.96), 0.8+/-2.0 l/min in those with 2nd degree TR
      (r=0.92), and 1.9+/-2.3 l/min in those with 3rd degree TR (r=0.69). CONCLUSIONS:
      A high degree of TR is associated with underestimation of cardiac output measured
      by thermodilution.

PMID- 12185435
TI  - Safe long-distance interhospital ground transfer of critically ill patients with
      acute severe unstable respiratory and circulatory failure.
AB  - OBJECTIVE: To assess the safety of long-distance ground interhospital transport
      of critically ill patients with the most severe unstable respiratory failure
      after establishment of a dedicated transport system. DESIGN AND SETTING: Cohort
      study, retrospective chart review in 13 hospitals and intensive care units (ICU)
      in Finland, and a tertiary referral center and ICU of a university hospital.
      PATIENTS: 66 consecutive critically ill patients who were transferred to our ICU
      from 13 different ICUs in Finland because of severe, progressive respiratory
      failure, 52 (79%) with acute respiratory distress syndrome. MEASUREMENTS AND
      RESULTS: Major complications during transfer and patients' oxygenation. The
      median transfer distance was 161 km (range 120-460 km). Drugs for cardiovascular
      support were infused in 59 patients (89%) during transfer. Fourteen patients
      (21%) were transferred in prone position because of life-threatening hypoxemia.
      The ratio of arterial blood PaO(2) and the fraction of oxygen in the ventilator
      was 8.5+/-2.7 kPa (64+/-20 mmHg) before transfer and 9.7+/-3.6 kPa (73+/-27 mmHg)
      after transfer. There were no major complications during the transfer. ICU
      mortality was 30%. CONCLUSIONS: Long-distance interhospital ground transfer of
      even critically ill patients with severe unstable respiratory and circulatory
      failure is safe if a dedicated transport team and a specially equipped transport
      vehicle are used.

PMID- 12185436
TI  - Severe cardiac failure in newborns with VGAM. Prognosis significance of
      hemodynamic parameters in neonates presenting with severe heart failure owing to
      vein of Galen arteriovenous malformation.
AB  - OBJECTIVE: Neonatal vein of Galen malformation complicated by severe cardiac
      failure is a rare disease. The purpose was to assess the outcome of this life
      threatening malformation and identify hemodynamic prognostic factors. DESIGN:
      Retrospective study. PATIENTS: Twenty-four newborns with cardiac failure
      requiring mechanical ventilation were consecutively admitted from 1986 to 2000.
      INTERVENTIONS: Cardiovascular evaluation including echocardiogram was performed
      in all cases. Eighteen transarterial shunt occlusions with glue were applied by
      the same team of three physicians. MEASUREMENTS AND RESULTS: Twelve babies
      survived and underwent one endovascular session at least (median age 20 days)
      with a mean 63 months follow-up. Embolization was not performed in 6 of the 12
      nonsurvivors because of severe brain damage or profound hypotension Cardiogenic
      shock occurred in all nonsurvivors, but also in one long-term survivor
      (p<0.0001). Echocardiogram showed signs of right ventricular failure, most often
      in the dead babies (p=0.005). The pulmonary systemic arterial pressure ratio was
      significantly higher in the nonsurvivor group (p=0.031), and it decreased
      significantly after the first embolization only in patients who survived
      (p=0.01). Patent ductus arteriosus and a diastolic aortic reversed-flow were
      present in all nonsurvivors in contrast to 30% of the long-term survivors
      (p=0.003 ). There was no difference in the left ventricular contractility and
      mean cardiac output between the two groups. CONCLUSIONS: The outcome of vein of
      Galen malformation complicated by severe cardiac failure requiring mechanical
      ventilation remains poor. Neonatal embolization seems to be beneficial only in
      babies without suprasystemic pulmonary hypertension.

PMID- 12185437
TI  - Exogenous surfactant reduces ventilator-induced decompartmentalization of tumor
      necrosis factor alpha in absence of positive end-expiratory pressure.
AB  - OBJECTIVE: To determine the effect of pretreatment with exogenous surfactant on
      ventilator-induced decompartmentalization of TNF-alpha. DESIGN AND SETTING:
      Prospective, randomized, animal study in the experimental laboratory of a
      university. SUBJECTS AND INTERVENTIONS: Male Sprague-Dawley rats (n=102) received
      lipopolysaccharide either intratracheally or intraperitoneally to stimulate TNF
      alpha production; one-half of the animals were pretreated with surfactant.
      Animals were ventilated for 20 min with a peak inspiratory pressure/positive end
      expiratory pressure (PEEP) ratio of either 45/0 or 45/10 (frequency 30 bpm, I/E
      ratio 1:2, FIO(2)=1). MEASUREMENTS AND RESULTS: Blood gas tension and arterial
      pressures were recorded 1, 10, and 20 min after the start of mechanical
      ventilation. After the animals were killed pressure-volume curves were recorded,
      and bronchoalveolar lavage was performed for assessment of protein content and
      the small/large surfactant aggregate ratio. TNF-alpha was determined in serum and
      bronchoalveolar lavage. Pretreatment with surfactant decreased
      decompartmentalization of TNF-alpha during 45/0 ventilation. Addition of a PEEP
      level of 10 cm H(2)O reduced decompartmentalization even further. In addition,
      surfactant prevented deterioration in oxygenation and decreased accumulation of
      protein in the bronchoalveolar lavage in the zero-PEEP group. CONCLUSIONS: An
      excess of active surfactant decreases transfer of cytokines across the alveolar
      capillary membrane similar to PEEP. The combination of PEEP and surfactant
      reduces decompartmentalization of TNF-alpha even further.

PMID- 12185438
TI  - Methylprednisolone does not enhance the surfactant effects on oxygenation and
      histology in paraquat-induced rat lung injury.
AB  - OBJECTIVE: To investigate whether exogenous surfactant would improve gas exchange
      and lung histology and methylprednisolone pretreatment would enhance the
      surfactant effect in a rat model of paraquat-induced lung injury. SETTING:
      University research facility. SUBJECTS: Thirty-three adult male Sprague-Dawley
      rats. INTERVENTIONS: All rats received intraperitoneal paraquat injection (35
      mg/kg) and were assigned randomly to one of four groups: the control group
      received no further treatment; the methylprednisolone group received a
      concomitant intraperitoneal methylprednisolone injection (30 mg/kg); the
      surfactant group received intratracheal Survanta (100 mg/kg) at the start of
      ventilation; and the methylprednisolone + surfactant group received both
      methylprednisolone and surfactant treatments. MEASUREMENTS AND MAIN RESULTS:
      Three days after paraquat injection, every rat was ventilated for 90 min, a
      static pressure-volume curve and bronchoalveolar lavage were performed and
      postmortem histology was examined. Treatment with surfactant and
      methylprednisolone + surfactant improved oxygenation relative to the control
      group and produced significantly higher lung volumes than the control and
      methylprednisolone groups. Treatment with surfactant resulted in a significant
      decrease in total cell and neutrophil counts relative to the control group.
      Surfactant with methylprednisolone pretreatment significantly decreased total
      cell, macrophage and neutrophil counts when compared with the surfactant group.
      The histological appearance of the lungs was better in the two surfactant-treated
      groups. CONCLUSION: Intratracheal instillation of surfactant improves gas
      exchange, ameliorates lung inflammation and results in less lung damage in
      paraquat-induced rat lung injury. Surfactant with methylprednisolone pretreatment
      decreases inflammatory cell infiltration, but cannot further improve oxygenation
      and lung histology.

PMID- 12185440
TI  - Oxygenation index, an indicator of optimal distending pressure during high
      frequency oscillatory ventilation?
AB  - OBJECTIVE: To test the hypothesis that, during high-frequency oscillatory
      ventilation (HFOV) of pigs with acute lung injury, the oxygenation index (OI =
      Paw*FIO(2)*100/PaO(2)) is minimal at the lowest continuous distending pressure
      (Paw), where the physiological shunt fraction is below 0.1 (Paw(optimal)). DESIGN
      AND SETTING: Prospective, observational study in a university research
      laboratory. SUBJECTS: Eight Yorkshire pigs weighing 12.0+/-0.5 kg, with lung
      injury induced by lung lavage. INTERVENTIONS: After initiation of HFOV, the pigs
      were subjected to a stepwise increase of Paw to obtain under-inflation, optimal
      inflation and over-distension of the lungs (inflation) in series, followed by a
      similar decrease of Paw (deflation). MEASUREMENTS AND RESULTS: At each Paw level,
      the OI and physiological shunt fraction were determined. The OI reached a minimum
      of 6.2+/-1.4 at Paw 30+/-4 cmH(2)O during inflation and a minimum of 2.4+/-0.3 at
      Paw 13+/-2 cmH(2)O during deflation. Paw(optimal) was 32+/-6 cmH(2)O on the
      inflation limb and 14+/-2 cmH(2)O on the deflation limb. The difference between
      the Paw at minimal OI and Paw(optimal) was -1.9+/-4.2 cmH(2)O (NS) during
      inflation and -1.5+/-1.6 cmH(2)O (p<0.05) during deflation. In 15 out of the 16
      comparisons, the difference in Paw was within one step (+/-3 cmH(2)O).
      CONCLUSION: The minimal OI is indicative for the Paw where oxygenation is optimal
      during HFOV in surfactant-depleted pigs.

PMID- 12185439
TI  - Diprivan attenuates the cytotoxicity of nitric oxide in cultured human bronchial
      epithelial cells.
AB  - OBJECTIVE: Excess nitric oxide (NO) and its reactive derivatives cause oxidative
      reactions that lead to cell death. Propofol, an intravenous anesthetic, exhibits
      antioxidant properties. Diprivan is a widely used commercial preparation of
      propofol that is emulsified in 10% intralipids. We sought to test the hypothesis
      that clinically encountered concentrations of Diprivan attenuate the toxicity of
      NO in a cell culture model. DESIGN: Prospective, randomized, controlled trial.
      SETTING: University research laboratory. SUBJECTS: Cultured human bronchial
      epithelial (IB-3) cells. INTERVENTIONS: Human bronchial epithelial cell cultures
      were randomly assigned to one of the following six groups: no additives (negative
      control), NO alone (positive control), NO with either 1 micro M, 10 micro M or
      100 micro M Diprivan, and 100 micro M Diprivan alone (Diprivan control). S
      nitroso-N-acetylpenicillamine (SNAP) was used to generate NO. MEASUREMENTS AND
      RESULTS: Hemacytometry with trypan blue staining was used to measure cell
      survival. To assess direct NO toxicity, immunoblot assays for nitrotyrosine
      containing proteins in cell homogenates were performed. Exogenous NO
      significantly decreased live cell numbers and increased intracellular
      nitrotyrosine-containing protein concentrations (p<0.001). Diprivan significantly
      attenuated these changes in a concentration-independent manner (p<0.001). At
      concentrations as low as 1 micro M, Diprivan exhibited cytoprotective effects.
      CONCLUSIONS: Diprivan effectively attenuates the cytotoxicity of excessive NO
      exposure in IB-3 cells at concentrations that are clinically attainable.

PMID- 12185441
TI  - Clinical experience with quinupristin-dalfopristin as rescue treatment of
      critically ill patients infected with methicillin-resistant staphylococci.
AB  - OBJECTIVES: To describe the efficacy and safety of quinupristin-dalfopristin (Q
      D) as rescue therapy in critically ill patients with severe infections caused by
      methicillin-resistant staphylococci unresponsive to vancomycin treatment. DESIGN:
      Observational study in the context of the compassionate use programme for Q-D.
      METHODS: Twelve mechanically ventilated patients suffering from severe
      staphylococcal infections, pretreated unsuccessfully with vancomycin despite in
      vitro sensitivity, were included. Patients received, intravenously, Q-D 7.5 mg/kg
      body weight 3 times daily. The duration of Q-D therapy averaged 11.8 days (range:
      1-26 days). The outcome variables were clinical efficacy and bacteriological
      eradication. RESULTS: Methicillin-resistant Staphylococcus aureus (MRSA) and
      Staphylococcus epidermidis (MRSE) were isolated in three patients each, and both
      bacteria were isolated from six patients. Eradication of pathogen(s) was achieved
      in 7 of 12 patients (66%). Five patients (42%) died due to severe co-morbidity.
      Adverse events related to Q-D were not observed and neither renal nor liver
      function was adversely affected. CONCLUSIONS: Quinupristin-dalfopristin appears
      to be an efficient and safe antimicrobial drug for the rescue treatment of
      staphylococcal infections in critically ill patients. It may be considered as a
      treatment option in cases of vancomycin treatment failure.

PMID- 12185442
TI  - The -260 C-->T promoter polymorphism of the lipopolysaccharide receptor CD14 and
      severe sepsis in trauma patients.
AB  - OBJECTIVE: CD14, expressed on the cell surface of monocytes and hepatic Kupffer
      cells, interacts with Gram-positive and Gram-negative bacteria. Upon CD14
      stimulation, these cells respond with the enhanced release of cytokines involved
      in the pathophysiology of sepsis. The purpose of this study was to evaluate
      whether the genotype distribution of the -260 C-->T promoter polymorphism of the
      CD14 gene is associated with the development of severe sepsis in trauma patients.
      PATIENTS AND PARTICIPANTS: Fifty-eight severely injured blunt trauma patients
      with an injury severity score of 16 or more and without pre-existing chronic
      diseases. MEASUREMENTS AND RESULTS: Genotyping for the single nucleotide exchange
      polymorphism of the CD14 gene was performed by means of a real-time polymerase
      chain reaction with fluorescence-labeled hybridization probes. Diagnosis of
      severe sepsis was based on the criteria of the ACCP/SCCM criteria. Fourteen out
      of the 58 patients (24.6%) developed a trauma-related severe sepsis. The overall
      allele frequency was 0.58 for the C allele and 0.42 for the T allele. The
      genotype distribution (TT 0.19, CT 0.47 and CC 0.35) did not differ significantly
      from a previously reported control group of healthy blood donors. There was no
      significant difference of the genotype distribution or allele frequency between
      trauma patients with severe sepsis and patients with an uncomplicated clinical
      course. CONCLUSIONS: This pilot study suggests that the CD14 -260 polymorphism is
      not associated with an increased risk of severe sepsis in trauma patients.

PMID- 12185443
TI  - Short-term cardiovascular effects of plasmapheresis in norepinephrine-refractory
      septic shock.
AB  - OBJECTIVE: To examine the short-term cardiovascular effects of plasmapheresis in
      seven patients (six surgical, one medical) with norepinephrine-refractory septic
      shock. DESIGN AND SETTING: Retrospective observational study in a secondary
      community hospital. INTERVENTIONS: Plasmapheresis was performed as follows: blood
      flow, 120 ml/min; exchange volume, 10 fresh frozen plasma (ca. 2200 ml) at rate
      of 13 ml/min; anticoagulation, unfractionated heparin 200-300/IU/h. Five patients
      received one separation and two patients three separations. All patients received
      norepinephrine intravenously (0.6+/-0.7 micro g/kg per minute) to achieve a mean
      arterial pressure of 77+/-12 mmHg. All patients received ventilatory support; two
      had acute oligoanuric renal failure treated by continuous hemodiafiltration.
      MEASUREMENTS AND RESULTS: We recorded heart rate, mean arterial pressure, central
      venous pressure, catecholamine dose, gas exchange, acid-base status, diuresis, C
      reactive protein, white blood cell count, and Simplified Acute Physiological
      Score II. Except for transitory decreases in central venous pressure no changes
      were found in any variable. Six of seven patients died 5+/-3 days after the last
      plasmapheresis. CONCLUSIONS: In patients with norepinephrine-refractory septic
      shock no directional changes in measured variables were found in the first 24 h
      after a plasmapheresis. Thus, regarding the cost (ca. 1000 euros per separation)
      and possible risks the procedure needs rigorous evaluation even as "rescue
      therapy" in patients with septic shock.

PMID- 12185444
TI  - Adrenal function in non-septic long-stay critically ill patients: evaluation with
      the low-dose (1 micro g) corticotropin stimulation test.
AB  - OBJECTIVE: To investigate the adrenal function in non-septic, long-stay
      critically ill patients. DESIGN: Prospective, consecutive study. SETTING: General
      intensive care unit in a university hospital. PATIENTS: Forty-three non-septic
      patients with protracted critical illness. INTERVENTIONS: A morning blood sample
      was first obtained to measure baseline plasma cortisol. Subsequently, 1 micro g
      of corticotropin (ACTH, Synacthene) was injected intravenously and 30 min later a
      second blood sample was drawn to determine stimulated plasma cortisol. Patients
      having a stimulated cortisol level of at least 18 micro g/dl were defined as
      responders. In 36 patients, morning interleukin-6 (IL-6) was also measured.
      MEASUREMENTS AND RESULTS: Baseline and stimulated plasma cortisol were 16.8+/-4.1
      micro g/dl and 21.2+/-5.1 micro g/dl, respectively. Interleukin-6 was high
      (median 39.3 pg/ml, interquartile range 24.9-86.6 pg/ml) and correlated
      negatively with stimulated plasma cortisol (r=-0.40, p<0.05). Of the 43 patients
      studied, 31 patients (72%) were responders and 12 patients (28%) were non
      responders to the ACTH stimulation test. Overall, 18 patients died and 25
      patients survived to hospital discharge. Non-responders had significantly higher
      IL-6 levels compared to responders (106+/-73 versus 48+/-42 pg/ml, p<0.05),
      whereas mortality rate was comparable in the two groups (50% versus 38%, p=0.74).
      CONCLUSIONS: Circulating plasma IL-6 levels are high during protracted critical
      illness, and are partially responsible for the relative adrenal insufficiency
      found in a subset of severely ill patients.

PMID- 12185445
TI  - Keeping central venous lines open: a prospective comparison of heparin, vitamin C
      and sodium chloride sealing solutions in medical patients.
AB  - OBJECTIVE: To prevent catheter occlusion, intermittently used central venous
      catheters are frequently sealed with vitamin C solution or heparin solution
      between use. The present study was designed to test the effectiveness of this
      approach and to compare the efficiency of sealing solutions. DESIGN AND SETTING:
      Prospective randomized study performed on a 9-bed medical ICU and on medical
      wards of an academic tertiary care center. PARTICIPANTS. Ninety-nine central
      venous line placements were prospectively included in the study and randomized
      into three treatment groups: sodium chloride 0.9%, vitamin C (200 mg/ml) and
      heparin (5000 IU/ml) sealing solutions. INTERVENTIONS AND MEASUREMENTS: Catheters
      were filled with the respective sealing solution and patency was tested once
      every 2 days using a standardized routine. Catheter patency was compared among
      the three groups using Kaplan-Meier statistics and log-rank testing. RESULTS:
      There was a significant difference in catheter patency between the three groups
      (p<0.03, log-rank test). A comparison of catheter survival between the catheters
      filled with heparin and those filled with sodium chloride, but not between those
      filled with vitamin C solution and with sodium chloride solution, exhibited
      significant differences in catheter patency (p<0.04, log-rank test). CONCLUSIONS:
      Local anticoagulation of intermittently used central venous catheters prolongs
      catheter patency. High-dose (5000 IU/ml) heparin solution is a useful
      anticoagulant for this purpose, while vitamin C solution does not prolong
      catheter patency.

PMID- 12185446
TI  - Physiological effects of translaryngeal open ventilation in patients with
      restrictive respiratory disorders.
AB  - OBJECTIVE: To compare the efficacy of pressure-controlled ventilation (PCV)
      delivered through a conventional endotracheal tube with the same ventilatory mode
      using a small-size tube with the cuff left deflated (translaryngeal open
      ventilation: TLOV). SETTING: A medical-surgical intensive care unit (ICU).
      DESIGN: Prospective physiological study. PATIENTS: Thirteen consecutive patients
      with restrictive neuromuscular and thoracic respiratory disorders ventilated in
      pressure-controlled mode. INTERVENTIONS: The standard tube was removed and a
      microlaryngeal tube (i.d. 4 mm, o.d. 6 mm, length 380 mm) was inserted with the
      cuff left deflated. PCV was increased to match the tracheal pressure measured
      during conventional ventilation. Arterial blood gases were measured before, 1 h
      and 20 h after initiating TLOV. A patient comfort score was measured by a visual
      analogue scale during conventional ventilation and 20 h after initiating TLOV (0=
      very bad, 1= bad, 2= quite bad, 3= sufficient, 4= good, and 5= very good).
      RESULTS: Inspiratory pressure was significantly increased from 16+/-5 cmH(2)O to
      68+/-13 cmH(2)O after 1 h and to 65+/-12 cmH(2)O after 20 h to match the tracheal
      pressure measured during conventional ventilation (CV) (p<0.005). No
      statistically significant differences were found in arterial blood gases and
      patient's respiratory rate before and after 1 and 20 h of TLOV. The comfort score
      was 1.3+/-0.4 and 3.6+/-0.4 during CV and TLOV, respectively, on a scale from 0
      to 5 (p<0.002). CONCLUSION: This study indicates that, in selected patients, TLOV
      was as efficient as conventional PCV.

PMID- 12185447
TI  - Histone acetyl transferases: a role in DNA repair and DNA replication.
AB  - In eukaryotic cells DNA is associated with proteins to form a complex known as
      chromatin. The dominant proteins within this chromatin complex are the histones,
      which are subject to a wide variety of covalent and reversible posttranslational
      modifications such as acetylation. A specialized family of enzymes, the histone
      acetyl transferases, catalyzes the transfer of acetyl groups from their
      cosubstrate acetyl-coenzyme A to lysine residues of histones. Acetylation of
      histone N-terminal lysine residues induces chromosomal changes and results in the
      loss of chromosomal repression that allows the successful transcription of the
      underlying genes. Analogously, in DNA repair and also DNA replication the
      chromosomal repression is thought to be relieved by such mechanisms. Recently
      several publications have provided evidence that histone acetyl transferases also
      modify nonhistone proteins and thereby regulate their activities. This review
      discusses various aspects of histone acetyl transferases and summarizes recent
      findings which suggest a role for histone acetyl transferases in DNA repair and
      DNA replication.

PMID- 12185448
TI  - Clinical features and molecular bases of neuroacanthocytosis.
AB  - The term acanthocytosis is derived from the Greek for "thorn" and is used to
      describe a peculiar spiky appearance of erythrocytes. Acanthocytosis is found to
      be associated with at least three hereditary neurological disorders that are
      generally referred to as neuroacanthocytosis. Abetalipoproteinaemia is an
      autosomal recessive condition, characterised by absence of serum apolipoprotein B
      containing lipoproteins leading to fat intolerance and fat-soluble vitamin
      deficiency. This results in a progressive spinocerebellar ataxia with peripheral
      neuropathy and retinitis pigmentosa. Chorea-acanthocytosis is also an autosomal
      recessive condition and is characterised by chorea, orofaciolingual dyskinesia,
      dysphagia, dysarthria, areflexia, seizures and dementia. Some of its features,
      including choreic movements, peripheral neuropathy with areflexia, elevated serum
      creatine kinase levels and myopathy are shared by another form of
      neuroacanthocytosis, McLeod syndrome. Patients affected by this X-linked disorder
      also show abnormal expression of Kell blood group antigens and a permanent
      haemolytic state. In addition to these cases, acanthocytosis is occasionally
      associated with other neurological disorders, such as Hallervorden-Spatz disease.
      For each of the neuroacanthocytosis syndromes we review the main clinical
      features and their molecular bases. The recent molecular genetics findings are
      the first step towards the understanding of the pathogenetic mechanisms and
      eventually the search for effective treatments.

PMID- 12185449
TI  - Functional consequences of angiotensin-converting enzyme gene polymorphism on N
      acetyl-Ser-Asp-Lys-Pro degradation and angiotensin II production.
AB  - Studies analyzing the biochemical and hemodynamic consequences of the
      insertion/deletion (I/D) polymorphism of the angiotensin I converting enzyme gene
      on angiotensin I and bradykinin metabolism have provided divergent results.
      Twelve DD and 12 II normotensive subjects were infused for 15 min with
      angiotensin I (30 ng kg(-1) x min(-1)) and with another angiotensin I converting
      enzyme substrate not related to the renin-angiotensin system, N-acetyl-Ser-Asp
      Lys-Pro (AcSDKP; 1.12 micro g kg(-1) x min(-1)), in the presence and absence of
      captopril. The infusion of the two peptides was repeated 15 days apart. In both
      the presence and the absence of captopril we found that DD and II subjects did
      not significantly differ in terms of endogenous plasma AcSDKP, angiotensin I, or
      angiotensin II concentrations, and that conversion of exogenous angiotensin I to
      angiotensin II was not faster in the DD subjects. Exogenously infused AcSDKP was
      metabolized slightly more rapidly in DD than in II subjects only when angiotensin
      I converting enzyme was not inhibited. The within-subject variability for
      angiotensin measurements was high, in contrast to AcSDKP measurements. This
      variability may account for the divergent results reported to date in the
      biochemical consequences of the I/D polymorphism of the angiotensin I converting
      enzyme gene. In conclusion, the I/D polymorphism of the angiotensin I converting
      enzyme gene has no effect on either endogenous AcSDKP metabolism or on the
      circulating renin-angiotensin system. It slightly affects the metabolism of
      exogenously infused AcSDKP and not that of angiotensin I.

PMID- 12185450
TI  - Inhibition of nonviral cationic liposome-mediated gene transfer into primary
      human respiratory cells by interferon-gamma.
AB  - The effect of interferon (IFN) gamma on cationic liposome-mediated gene transfer
      into primary respiratory epithelial cells was investigated. Treatment of primary
      respiratory epithelial cells with IFN-gamma resulted in a dose-dependent increase
      in the intermediate filament cytokeratin 13 and a decrease in cellular
      proliferation, indicating that respiratory cells underwent squamous
      differentiation. IFN-gamma pretreatment resulted in a dramatic inhibition of
      transfection efficiency mediated by a cationic liposome (DOTAP). Incubation of
      squamous nasal cells with DOTAP/DNA complexes for various periods at 4 degrees C
      and evaluation of luciferase levels suggested that IFN-gamma pretreatment
      inhibits complex binding to the cells. In primary nasal and bronchial cells
      cytofluorimetric analysis demonstrated that IFN-gamma reduces binding of FITC
      labeled complexes. The data indicate that differentiation of respiratory
      epithelial cells to a squamous phenotype, which may occur in chronic respiratory
      diseases such as cystic fibrosis, induces a refractory condition to gene transfer
      by nonviral cationic liposomes.

PMID- 12185451
TI  - The interleukin-6 G(-174)C promoter polymorphism in the LURIC cohort: no
      association with plasma interleukin-6, coronary artery disease, and myocardial
      infarction.
AB  - IL-6 plasma levels are predictive of major cardiovascular events. Recently a G/C
      polymorphism at position -174 in the promoter of the IL-6 gene has been
      associated with differences in both the IL-6 transcription rate in vitro and IL-6
      levels in vivo. We examined the association of this polymorphism with coronary
      artery disease (CAD) and previous myocardial infarction (MI) in 2559 patients
      with angiographically documented CAD with ( n=1365) and without ( n=1194) MI and
      in a control group of 729 individuals in whom CAD had been ruled out
      angiographically. Assuming dominant or recessive modes of inheritance, carriers
      of the G allele had odds ratios of 0.98 (95% CI 0.79 - 1.20) and 0.96 (95% CI
      0.80 - 1.14), respectively, for CAD, and almost identical ones for previous MI.
      In subgroups stratified for low cardiovascular risk, the IL-6 promoter
      polymorphism was also not related to the risk of CAD or MI. In addition, the
      plasma concentration of IL-6 did not differ between groups with different IL-6
      genotypes in 942 randomly selected individuals. We conclude that the IL-6 G(
      174)C polymorphism is not associated with the risk of CAD or MI and does not
      contribute to cardiovascular risk stratification.

PMID- 12185452
TI  - TGF-beta(1) gene modified immature dendritic cells exhibit enhanced
      tolerogenicity but induce allograft fibrosis in vivo.
AB  - Administration of donor-derived immature dendritic cells (DC) can prolong the
      survival of MHC-mismatched cardiac allografts. Genetic modification of DC by
      immunosuppressive molecules can enhance their potential tolerogenicity. In this
      study bone marrow derived immature DC were genetically modified by transforming
      growth factor (TGF) beta1 by recombinant Ad. TGF-beta(1) gene modified immature
      DC (TGF-beta-DC) displayed a characteristic phenotype of immature DC, decreased
      ability to secrete interleukin 12, and reduced allostimulatory ability. TGF-beta
      DC induced alloantigen-specific T cell hyporesponsiveness in vitro and in vivo,
      and Th2 cytokine polarization. mRNA expression of donor MHC class II (Ia(b)) and
      human TGF-beta(1) was detected in spleen and lymph nodes of the allogeneic
      recipients for 3 weeks after TGF-beta-DC infusion, indicating that microchimerism
      of TGF-beta-DC is exhibited in allogeneic recipients. In this murine cervical
      heterotopic heart transplantation model, the survival of the allograft in
      recipients intravenously infused with TGF-beta-DC 7 days before transplantation
      was greatly prolonged, and about 67% of cardiac grafts survived more than 40
      days. Histological analysis of the allografts showed that the normal myocardial
      architecture was well preserved, accompanied by very little necrotic cells, but
      interstitial fibrosis replaced myocytes, and moderate collagen suffused the whole
      cardiac allograft in the recipients infused with TGF-beta-DC. mRNA expression of
      type III procollagen was markedly increased in the allografts of the recipients
      infused with TGF-beta-DC. Our results suggest that infusion of TGF-beta(1) gene
      modified immature DC prolongs the survival of the allograft through the effective
      induction of donor-specific T cell hyporesponsiveness. However, TGF-beta(1)
      expressed by gene modified immature DC can cause the fibrosis of the allografts,
      which may limit the application of this approach in the allograft
      transplantation.

PMID- 12185453
TI  - Identification and functional characterization of a novel KCNE2 (MiRP1) mutation
      that alters HERG channel kinetics.
AB  - Long-QT syndrome (LQTS) may cause syncope and sudden death due to cardiac
      tachyarrhythmia. Chromosome 7-linked LQTS (LQT2) has been correlated with
      mutations in the human ether-a-go-go-related gene (HERG). HERG forms voltage
      gated K channels that may be associated with Mink-related peptide 1 (MiRP1), an
      auxiliary beta-subunit. The channels mediate currents that resemble native I(Kr).
      Mutations in the KCNE2 gene encoding MiRP1 may also cause LQTS. In this study,
      the frequency of mutations in KCNE2 of 150 unrelated LQTS patients without known
      genotype and of 100 controls was analyzed using single-strand conformation
      polymorphism analysis and direct sequencing. We identified a novel missense
      mutation, V65 M, in the KCNE2 gene of a 17-year-old female with syncope and LQTS.
      Expression studies in Chinese hamster ovary cells revealed that mutant and wild
      type MiRP1 co-localized with HERG subunits and formed functional channels.
      However, mutant HERG/MiRP1(V65M) channels mediated currents with an accelerated
      inactivation time course compared with wild-type channels. The accelerated
      inactivation time course of HERG/MiRP1(V65M) channels may decrease I(Kr) current
      density of myocardial cells, thereby impairing the ability of myocytes to
      repolarize in response to sudden membrane depolarizations such as extrasystoles.

PMID- 12185454
TI  - Naive CD8(+) but not CD4(+) T cells induce maturation of dendritic cells.
AB  - We have shown previously that the generation of tumor-reactive CD8(+) cytotoxic T
      lymphocytes require qualitatively different signals from CD4(+) and CD8(+) T
      cells that most likely are provided to dendritic cells (DCs). This raises the
      question of whether the two T cell subsets are equally able to deliver the
      initial activation signal to DCs. Using ovalbumin as a model antigen we show that
      naive CD4(+) T cells cannot activate immature DCs and do not become activated,
      even though they recognize antigen on immature DCs. In contrast, naive CD8(+) T
      cells rapidly activate DCs and subsequently start to proliferate. This suggests
      that CD8(+) T cells contribute to DC activation prior to CD4(+) T cells and
      implies that CD8(+) T cells can provide help to CD4(+) T cells.

PMID- 12185456
TI  - Resampling methods for variance estimation of singular value decomposition
      analyses from microarray experiments.
AB  - Microarray experiments offer the ability to generate gene expression measurements
      for thousands of genes simultaneously. Work has begun recently on attempting to
      reconstruct genetic networks based on analyses of microarray experiments in time
      course studies. An important tool in these analyses has been the singular value
      decomposition method. However, little work has been done on assessing the
      variability associated with singular value decomposition analyses. In this
      report, we discuss use of the bootstrap as a method of obtaining standard errors
      for singular value decomposition analyses. We consider use of this method both
      when there are replicates and when no replicates exist. The proposed methods are
      illustrated with an application to two datasets: one involving a human foreskin
      study, the other involving yeast.

PMID- 12185455
TI  - Functional genomics in the mouse.
AB  - The mouse is the premier genetic model organism for the study of human disease
      and development. With the recent advances in sequencing of the human and mouse
      genomes, there is strong interest now in large-scale approaches to decipher the
      function of mouse genes using various mutagenesis technologies. This review
      discusses what tools are currently available for manipulating and mutagenizing
      the mouse genome, such as ethylnitrosourea and gene trap mutagenesis, engineered
      inversions and deletions using the cre-lox system, and proviral insertional
      mutagenesis in somatic cells, and how these are being used to uncover gene
      function.

PMID- 12185457
TI  - Quantitative trait loci (QTL) for lean body mass and body length in MRL/MPJ and
      SJL/J F(2) mice.
AB  - Studies on the genetic mechanisms involved in the regulation of lean body mass
      (LBM) in mammals are minimal, although LBM is associated with a competent immune
      system and an overall good (healthy) body functional status. In this study, we
      performed a high-density genome-wide scan using 633 (MRL/MPJ x SJL/J) F(2)
      intercross to identify the quantitative trait loci (QTL) involved in the
      regulation of LBM. We hypothesized that additional QTL can be identified using a
      different mouse cross (MRL/SJL cross). Ten QTL were identified for LBM on
      chromosomes (chrs) 2, 6, 7, 9,13 and 14. Of those ten, QTL on chrs 6, 7 and 14
      were exclusive to LBM, while QTL on chrs 4 and 11 were exclusively body length.
      LBM QTL on chrs 2 and 9 overlap with those of size. Altogether, the ten LBM QTL
      explained 41.2% of phenotypic variance in F(2) mice. Five significantly
      interacting loci that may be involved in the regulation of LBM were identified
      and accounted for 24.4% of phenotypic variance explained by the QTL. Five
      epistatic interactions, contributing 22.9% of phenotypic variance, were
      identified for body length. Interacting loci on chr 2 may influence LBM by
      regulating body length. Therefore, epistatic interactions as well as single QTL
      effects play an important role in the regulation of LBM.

PMID- 12185458
TI  - Global gene expression patterns during differentiation of F9 embryonal carcinoma
      cells into parietal endoderm.
AB  - Expression levels of over 8,900 murine genes were examined, using cDNA
      microarrays, during the differentiation of F9 cells into parietal endoderm
      following exposure to retinoic acid/dibutyryl cAMP. Gene induction and repression
      over the time course exhibited a biphasic pattern consistent with a transition
      from undifferentiated F9 cells to primitive endoderm and finally parietal
      endoderm. A 6-h induction with retinoic acid/cAMP/cycloheximide resulted in 109
      candidate immediate response genes. During a 9-day time course 516 genes were
      selected as being significantly induced/repressed. Several of these genes had
      been previously identified as having altered expression patterns in F9 cells
      undergoing differentiation by retinoic acid/cAMP. Functional characterization of
      these genes demonstrated that the majority were transcription factors while
      others included surface antigens and genes involved in intracellular transport.
      Cluster analysis, utilizing both a hierarchical algorithm and self-organizing
      map, resulted in very similar gene clusters. Our studies revealed an extremely
      complex set of interacting signals that decide between cell death,
      differentiation, cell cycle withdrawal, and ultimately the traits associated with
      the terminal differentiated parietal endoderm cell type. The sets of genes
      identified here can now be modulated in a rational way to try to understand their
      role in differentiation.

PMID- 12185459
TI  - Quantitative trait loci that harbor genes regulating muscle size in (MRL/MPJ x
      SJL/J) F(2) mice.
AB  - The genetic mechanisms that determine muscle size have not been elucidated, even
      though it is a key musculoskeletal parameter that reflects muscle strength. In
      this study, we performed a high-density genome-wide scan using 633 (MRL/MPJ x
      SJL/J) F(2) intercross 7-week-old mice to identify quantitative trait loci (QTL)
      involved in the determination of muscle size. Significant QTL were identified for
      muscle size and body length. Muscle size (adjusted by body length) QTL were
      identified on chromosomes 7, 9, 11, 14 (two QTL) and 17, which together explained
      19.2% of phenotypic variance in F(2)mice, while body length QTL were located on
      chromosome 2 (two QTL), 9, 11 and 17 which accounted for 28.3% of phenotypic
      variance in F(2) mice. Three significant epistatic interactions between different
      QTL positions from muscle size and body length were identified ( P <0.01) on
      chromosomes 2, 9, 14 and 17, which explained 16.1% of the variance in F(2) mice.

PMID- 12185460
TI  - Comparing three methods for variance estimation with duplicated high density
      oligonucleotide arrays.
AB  - Microarray experiments are being increasingly used in molecular biology. A common
      task is to detect genes with differential expression across two experimental
      conditions, such as two different tissues or the same tissue at two time points
      of biological development. To take proper account of statistical variability,
      some statistical approaches based on the t-statistic have been proposed. In
      constructing the t-statistic, one needs to estimate the variance of gene
      expression levels. With a small number of replicated array experiments, the
      variance estimation can be challenging. For instance, although the sample
      variance is unbiased, it may have large variability, leading to a large mean
      squared error. For duplicated array experiments, a new approach based on simple
      averaging has recently been proposed in the literature. Here we consider two more
      general approaches based on nonparametric smoothing. Our goal is to assess the
      performance of each method empirically. The three methods are applied to a colon
      cancer data set containing 2,000 genes. Using two arrays, we compare the variance
      estimates obtained from the three methods. We also consider their impact on the t
      statistics. Our results indicate that the three methods give variance estimates
      close to each other. Due to its simplicity and generality, we recommend the use
      of the smoothed sample variance for data with a small number of replicates.

PMID- 12185461
TI  - Clinical trials, immunosuppression and renal transplantation: new trends in
      design and analysis.
AB  - Clinical trials provide a framework to search for more effective and less toxic
      immunosuppressive agents to control renal transplant rejection. Some
      methodological aspects are presented. Patient selection and the choice of study
      endpoints are discussed with emphasis on standardized definitions and
      classification of histopathology, and on qualification and quantification of
      chronic rejection. Choosing a Bayesian or a frequentist approach and the afferent
      hypotheses is discussed together with the interpretation of a P-value and a
      confidence interval. Strategies for limiting the number of patients, increasing
      power and feasibility are reviewed, including discussion of surrogate endpoints.
      New approaches to statistical analysis are then presented, including intention-to
      treat versus per-protocol analysis, analysis of correlated data, dependent
      censoring, and meta-analysis applied to renal transplantation. Pharmacoeconomics
      are finally introduced as necessary for implementation of decision making
      regarding therapeutic strategies. Reporting research increases its standards, and
      the CONSORT (Consolidated Standards of Reporting Trials) and QOROM (Quality of
      Reporting of Meta-analyses) criteria are to be integrated in the process of
      clinical trial procedures. In conclusion, observational studies are presented as
      part of an evidence-based approach in the hierarchy of evidence, keeping in mind
      that high quality, randomized, controlled trials are still necessary to decrease
      uncertainty in the field of renal transplantation.

PMID- 12185462
TI  - Growth hormone and growth hormone-related mRNA in uremic rats: effect of a growth
      hormone secretagogue.
AB  - In experimental animals, the decreased growth during mild uremia is not
      accompanied by a loss in the capacity of the pituitary gland to secrete growth
      hormone (GH). With the development of orally administered GH "secretagogues"
      (GHS), it might be possible to stimulate growth during uremia without injections.
      This study was designed to determine the effects of the GHS, L-163,255. Uremia
      was induced by 5/6 nephrectomy (NX). GHS was given orally, 3 mg/kg, twice a week.
      Four groups of animals included: (1) sham-operated, (2) sham-operated, pair-fed,
      (3) uremic (NX), and (4) uremic, GHS-treated (NX+GHS). Blood sampling was
      conducted via intra-atrial catheters, and GH was quantitated. Pituitary GH mRNA
      was measured by Northern blot, and liver GH receptor and insulin-like growth
      factor-I mRNAs by RNAase protection. Untreated NX animals had a specific decrease
      in the "mass" of the GH pulses. A burst of GH was induced by GHS, but the
      pulsatile pattern of GH secretion over 6 h was not affected. An increase or a
      return to non-uremic levels of GH-related mRNAs occurred after GHS. Thus, GHS
      stimulated an acute burst of GH secretion and increased specific mRNAs encoding
      GH-related proteins in uremic animals.

PMID- 12185464
TI  - Primary hyperoxaluria type 2 in children.
AB  - The primary hyperoxalurias (PH1 and PH2) are rare defects of oxalate
      overproduction. There are only 24 reported cases of PH2, which is characterized
      by raised urine oxalate and L-glycerate. We describe 13 previously unreported
      children with PH2, representing the largest single-centre cohort in the world.
      DNA samples were tested for a common mutation and four other documented mutations
      in the gene encoding the enzyme glyoxylate reductase/hydroxypyruvate reductase
      (GRHPR). Two of the five kindred showed homozygosity for two different mutations
      in the GRHPR gene. The genetic defect was not identified in the other three
      families. The median age at diagnosis of PH2 was 1.7 years. Five children
      presented with nephrolithiasis between 0.8 and 9 years. Haematuria was common,
      but urinary tract infection and nephrocalcinosis were not. All had normal renal
      function at diagnosis, and only 1 patient had a significant decline in glomerular
      filtration rate. We conclude that all children with nephrolithiasis secondary to
      hyperoxaluria should have urinary glycerate measured, as PH2 may be more
      prevalent than currently estimated. DNA mutational analysis may be useful in
      supporting the diagnosis.

PMID- 12185463
TI  - Renal cortical nitric oxide synthase activity during maturational growth in the
      rat.
AB  - The present study was designed to test the hypothesis that growth from puberty to
      adulthood in the rat is associated with an increase in renal cortical nitric
      oxide synthase (NOS) activity that results in an augmented impact of nitric oxide
      (NO) on hemodynamic function. Two groups of male Sprague-Dawley rats were
      studied: juvenile rats (approximately 2 months old) and mature rats
      (approximately 5 months old). NOS activity, measured as -nitro-L-arginine (NNA)
      sensitive (3)H-L-citrulline production from (3)H-L-arginine, was significantly
      higher in the renal cortex of mature rats (57+/-2 pmol/h per mg protein) than in
      juveniles (42+/-3 pmol/h per mg protein). Additional animals from each group were
      anesthetized to determine the acute impact of NOS inhibition on arterial pressure
      and renal cortical blood flow, measured by single-fiber Doppler flowmetry.
      Cortical blood flow was higher in mature rats than in juveniles, averaging 22+/-2
      and 16+/-1 perfusion units, respectively. NOS inhibition (10 mg/kg NNA i.v.)
      decreased renal cortical blood flow in mature rats by 35+/-7%, but only by 9+/-4%
      in juvenile animals. These data support the hypothesis that maturational growth
      in the rat is associated with augmented NOS activity coupled with an increased
      tonic influence of NO on renal cortical blood flow.

PMID- 12185465
TI  - Follow-up of five patients with FHHNC due to mutations in the Paracellin-1 gene.
AB  - Familial hypomagnesemia, hypercalciuria and nephrocalcinosis (FHHNC) is a rare
      autosomal recessive inherited disorder that has recently been attributed to a
      defect in the paracellin-1 ( PCLN-1)gene, encoding for a protein responsible for
      the tubular reabsorption of magnesium and calcium. Limited information is
      available on clinical course, therapy and prognosis. We provide information on
      five patients with FHHNC and their follow-up at our institution. Polyuria,
      nephrocalcinosis and hyperuricemia were the main clinical findings of a diagnosis
      at a median age of 4.4 years. The clinical course of PCLN-1 mutations as
      presented in this study is highly variable, ranging from compensated renal
      failure to end-stage renal failure - as happened in two of our patients. The
      progression to renal failure cannot be deduced from the initial presentation.
      Medical treatment does not appear to influence the progression of the disease.
      Despite calcium and magnesium substitution, normal values could not be achieved
      in these patients. Early treatment with vitamin D and calcium was essential to
      maintain growth. Adequate treatment allows for a normal height and pubertal
      development.

PMID- 12185466
TI  - Liddle syndrome in a newborn infant.
AB  - A 10-week-old female infant developed hypertension. The elevated blood pressure
      was associated with metabolic alkalosis and urinary chloride wastage. The family
      history was unremarkable. Her urinalysis, blood urea nitrogen (BUN), and serum
      creatinine concentrations were all normal. A renal ultrasound was normal. A
      technetium-99m diethylenetriaminopentoacetic acid (DTPA) renal scan with
      captopril showed normal blood flow bilaterally. The head ultrasound and
      echocardiogram were normal. Blood epinephrine, norepinephrine, catecholamines,
      thyroxine, and steroid levels were also normal. Treatment with various
      combinations of labetalol, hydralazine, captopril, methyldopa, nifedipine, and
      spironolactone, all at high doses, failed to control the elevated blood pressure.
      Serum aldosterone level and peripheral plasma renin activity were low. The lack
      of therapeutic response to spironolactone, with a good response to amiloride and
      recurrence of hypertension and metabolic alkalosis after amiloride cessation that
      was subsequently treated with amiloride, established the diagnosis of Liddle
      syndrome. To our knowledge, this is the youngest patient with Liddle syndrome
      that has been reported in the literature.

PMID- 12185467
TI  - Reevaluation of the criteria for the clinical diagnosis of Gitelman syndrome.
AB  - A 16-year-old female had mutations in both alleles of the gene encoding her
      sodium-chloride cotransporter; one of these mutations is newly described. Her
      clinical findings were not typical because of the absence of hypocalciuria in 24
      h urine samples, her maximum urine osmolality (U(osm)) was only 802 mosmol/kg
      H(2)O, and her plasma magnesium (Mg) concentration (P(Mg)) was easily maintained
      in the normal range with oral Mg supplements for 1 month. In detailed studies,
      the calcium/creatinine ratio in spot urines with a U(osm) >700 mosmol/kg H(2)O
      was very low, except during Mg therapy. Renal medullary function did not appear
      to be compromised because she had a non-urea U(osm)of approximately 600 mosmol/kg
      H(2)O, reflecting a very high non-urea osmole excretion rate (due to KCl
      supplements). At age 18 years, her P(Mg) became persistently low despite Mg
      therapy. We conclude that the clinical criteria for a provisional diagnosis of
      Gitelman syndrome should be revised. Hypocalciuria may only be evident initially
      in concentrated spot urine samples. Urine concentrating ability should include an
      analysis of the non-urea U(osm), especially when patients are taking large KCl
      supplements.

PMID- 12185468
TI  - Reflux nephropathy in a patient with crossed renal ectopia with fusion.
AB  - Crossed renal ectopia with fusion is a rare congenital anomaly of the urinary
      tract. While vesicoureteral reflux has been noted frequently, reflux nephropathy
      has rarely been reported with this anomaly. I describe here a case of reflux
      nephropathy in a patient with crossed renal ectopia with fusion. A 14-year-old
      boy was referred to our hospital for further examination of proteinuria, detected
      by the school's annual urinary screening program. Laboratory study revealed
      proteinuria and renal insufficiency. Abdominal computed tomography and voiding
      cystography disclosed crossed renal ectopia with fusion and vesicoureteral reflux
      in each moiety. Renal biopsy of the orthotopic kidney showed diffuse interstitial
      fibrosis and mononuclear cell infiltration, periglomerular fibrosis, glomerular
      hypertrophy, and focal and global glomerulosclerosis, which were compatible with
      reflux nephropathy. A low-protein diet and an administration of angiotensin
      converting enzyme inhibitor decreased the urinary excretion of protein.

PMID- 12185469
TI  - Adrenomedullin and nitrite levels in children with primary nocturnal enuresis.
AB  - Primary nocturnal enuresis (PNE) is the most common type of nocturnal enuresis in
      children, but its etiology remains unclear. Recent studies indicated the
      differences in urinary electrolytes in enuretic children, and stressed the
      existence of a renal tubular maturation defect. In this study, 30 children (aged
      6-12 years) with PNE were investigated in comparison with 18 healthy controls. We
      evaluated plasma antidiuretic hormone, electrolytes, 24-h urine volume,
      osmolarity, and urinary electrolytes. Unlike other studies, we firstly assessed
      the plasma and urinary adrenomedullin (AM) and total nitrite levels, a stable
      product of nitric oxide (NO), and investigated their relationship with urinary
      electrolytes. The plasma AM and total nitrite levels were significantly lower
      than controls. Urine volume (24-h) and potassium excretion were higher than in
      controls. However, 24-h urinary osmolarity and excretion of AM were significantly
      lower than in controls. Our results indicate that there may be a problem in renal
      regulation of potassium in children with PNE. Although decreased levels of AM and
      total nitrite may be a compensatory response to abnormal potassium and water
      excretion, further investigations are required to exclude whether the renal
      synthesis of AM and NO are also deficient in these children.

PMID- 12185470
TI  - Acute renal failure following massive attack by Africanized bee stings.
AB  - Bee venom is a complex substance, which acts in several tissues. Although severe
      allergic reactions have occurred after one or more stings, several deaths have
      been reported without allergic manifestations, emphasizing the toxic effects of
      massive poisoning. A number of about 500 stings have been considered necessary to
      cause death by direct toxicity, but as few as 30-50 stings have proved fatal in
      children. Among the major toxic effects are hemolytic anemia, acute renal failure
      (ARF), and shock. ARF may be due to a common toxic-ischemic mechanism with
      hypovolemic or anaphylactic shock, pigment tubulopathy (myoglobinuria and
      hemoglobinuria), or acute tubular necrosis (ATN) from a direct kidney toxicity of
      the venom. We present a case of rhabdomyolysis and hemolysis with consequent ARF
      which developed after about 800 bee stings. The patient recovered completely
      after peritoneal dialysis.

PMID- 12185471
TI  - Unexplained acute renal failure in a toddler: a rare complication of Epstein-Barr
      virus.
AB  - A previously healthy toddler developed severe acute renal failure with
      nephromegaly and peripheral atypical lymphocytosis. Profound interstitial
      nephritis with acute tubular necrosis was diagnosed by renal biopsy, and both the
      clinical picture and serological evaluation suggested Epstein-Barr virus (EBV) as
      the etiological agent. The previous reports of EBV-induced renal failure and the
      clinical and pathological presentations of interstitial nephritis in children are
      reviewed.

PMID- 12185472
TI  - Combination of ceftriaxone and acyclovir - an underestimated nephrotoxic
      potential?
AB  - Management of meningo-encephalitis often involves the need for antibiotic and
      antiviral treatment. We report a retrospective analysis over a 6-month period of
      17 patients (age range 1-14 years) who were treated with combination therapy of
      ceftriaxone and acyclovir. Mean acyclovir and ceftriaxone doses were 1,222+/-304
      and 2,315+/-509 mg/m(2) per day, respectively. Three patients developed acute
      renal failure with a peak creatinine of up to 865% above baseline, occurring 2-3
      days after starting combination therapy. Patients revealed a tubular proteinuria
      pattern. Renal biopsy of 1 patient showed a tubulotoxic picture but no evidence
      of crystals. In 12 of 17 patients (70%) there was a significant increase in serum
      creatinine. This was significantly greater than literature reports of 16% with
      acyclovir monotherapy. The degree of renal impairment in our patients correlated
      significantly with the acyclovir dose, while no correlation was found with the
      ceftriaxone dose. We conclude that the addition of a second nephrotoxic drug
      aggravated the extent of renal injury in our patients. The mechanism is
      tubulotoxicity. Caution should be exercised when using this potentially
      nephrotoxic cocktail, with clear criteria established for the initiation of
      combination therapy and close monitoring of serum creatinine.

PMID- 12185473
TI  - Immunization in children with chronic renal failure.
AB  - Infections jeopardize children on immunosuppression after organ transplantation.
      Immunization is protective in healthy children. The aims of this study were to
      analyze the rate and efficacy of immunization in 62 children undergoing dialysis
      and renal transplantation (RTPL) between 1987 and 2000. The analysis was based on
      clinical findings, vaccination certificates, and measurement of specific serum
      antibodies. A member of the renal unit administered vaccinations. All 62 patients
      were immunized against diphtheria, tetanus, pertussis, poliomyelitis, measles,
      mumps, rubella, and hepatitis B. Since introduction in 1991 and 1995, 44 and 42
      children were also vaccinated against influenza and Hemophilus influenzae type b,
      respectively. Of 16 patients with a negative history, 14 were given varicella
      vaccine; 16 children on peritoneal dialysis (PD) or with nephrotic syndrome were
      immunized against Streptococcus pneumoniae. All vaccinated patients had
      detectable serum antibodies against measles, mumps, rubella, varicella, hepatitis
      B, H. influenzae, and S. pneumoniae. There were 3 infections despite vaccination;
      1 patient developed varicella after RTPL and 1 patient on PD had 2 episodes of
      peritonitis caused by H. influenzae and S. pneumoniae. In conclusion, monitoring
      and administration of the vaccines by the renal team enabled a high immunization
      rate. Whether vaccines, as documented by antibody titers, or by the low
      prevalence in the general population promoted the low prevalence of infections
      remains open, as there were at least a few vaccination failures.

PMID- 12185474
TI  - Serum leptin and IGF-I during growth hormone treatment in chronic renal failure.
AB  - Serum leptin decreases during growth hormone (hGH) treatment and pre-treatment
      values have been suggested as a predictor of the response to hGH in GH deficiency
      (GHD) but not in non-GHD syndromes. To investigate whether this holds true in
      children with chronic renal failure (CRF), we evaluated changes in serum leptin,
      insulin-like growth factor-I (IGF-I) and height before(b) and during the 1st year
      (3 months, 6 months, 9 months, 12 months) of hGH treatment (1 IU/kg per week) in
      11 children (median age(b) 10.1 years, mean height(b) -2.9 SDS) with CRF. Serum
      leptin and IGF-I were compared with values from healthy children. Each patient
      also served as his/her own control, with values during treatment compared with
      those before treatment. Growth improved in all patients during treatment (mean
      change(12 m) +7.2 cm, change in height SDS(12 m) +0.5, P=0.001). Weight decreased
      (median decrease(12 m) 0.3 SDS, P=0.02) but body mass index (BMI) and serum
      leptin did not change during treatment. Serum IGF-I levels were low before (mean 
      1.1 SDS) but increased during hGH treatment, the increment being greatest at 10
      days (mean increment +1.9 SDS, P<0.0001). Serum leptin(b) did not correlate with
      change in serum IGF-I(10d), height(12 m) or weight(12 m). Serum IGF-I SDS(b)
      correlated with height SDS at 12 months ( r=0.80, P=0.006) of hGH treatment.
      Serum leptin(b) correlated with BMI ( r(s)=0.75, P=0.01). Levels adjusted for BMI
      did not differ from values in healthy children and did not change during
      treatment. Despite an IGF-I and growth response during hGH treatment, serum
      leptin did not change and pre-treatment values did not predict the growth
      response in these children with CRF.

PMID- 12185475
TI  - Sources of information on renal conditions used by families.
AB  - Information for families on their child's renal condition is an essential part of
      clinical care and our unit has produced a number of booklets and audiovisual
      materials. We wished to evaluate whether our information strategy needed to be
      updated, especially with the increasing use of the internet. Families attending
      general renal (GR) ( n=84) or chronic renal failure (CRF) ( n=42) clinics
      completed a questionnaire about the sources of information they had used. The
      commonest source was booklets (86% of CRF and 48% of GR, respectively). Many of
      the CRF group obtained information from other families, members of the
      multidisciplinary team, and television programmes. Internet usage was quoted by
      23% of families from the CRF group and 20% of the GR group. The survey encourages
      us to continue updating our present booklets and audiovisual materials with
      development of material for internet use. Renal units should be encouraged to
      assess their own information strategy.

PMID- 12185476
TI  - Effect of cisapride on rate-corrected QT intervals in children on peritoneal
      dialysis.
AB  - The aim of this study was to investigate whether cisapride significantly
      increases corrected QT (QTc) intervals on resting 12-lead electrocardiograms
      (ECGs) in children on peritoneal dialysis. Medical records of children who were
      treated with chronic peritoneal dialysis and who had ECGs while off and on
      cisapride were obtained and reviewed. QTc on all 12-lead ECGs and past medical
      history were analyzed by two blinded pediatric cardiologists. A total of 79 ECGs
      (68 off/11 on cisapride) for 11 children on peritoneal dialysis were included. Of
      11 children, 5 developed a prolongation of QTc, 2 of them beyond the normal range
      (453 and 478 ms). Mean data of QTc off versus on cisapride were 394+/-24 ms and
      414+/-36 ms, respectively ( P=0.041). In 4 of the 5 children concomitant
      medications could be identified as factors to explain prolongation of the QT
      interval. No child had evidence of any arrhythmia or conduction defect on ECG.
      This retrospective study found mild but significant increases in QTc intervals
      with cisapride in children on chronic peritoneal dialysis, mostly due to
      concomitant medications.

PMID- 12185478
TI  - Conversion from cyclosporine to tacrolimus in pediatric kidney transplant
      recipients.
AB  - In pediatric kidney transplant recipients, tacrolimus has been proposed either
      for primary immunosuppression or as a rescue agent for refractory acute
      rejection, chronic rejection, and cyclosporine toxicity. This paper describes our
      experience with tacrolimus conversion from cyclosporine-based therapy in six
      selected cases: four due to refractory acute rejections unresponsive to
      conventional therapy, one to chronic graft rejection, and one to cyclosporine
      related hypertrichosis. A "simple-switch" conversion was used without any
      overlap, starting with a dose of 0.2 mg/kg per day. The time to conversion varied
      from 10 to 730 days after the transplant. In the patients with acute rejection,
      the median time to reversal after tacrolimus conversion was 12 days. The symptoms
      of the patient with cyclosporine toxicity completely resolved without any loss of
      allograft function. The patient with chronic rejection maintained stable renal
      function for more than 1 year after conversion. A new onset of post-transplant
      diabetes mellitus and dose-related nephrotoxicity were recorded as adverse
      events. In conclusion, our experience suggests that tacrolimus can play an
      important role in the salvage treatment of pediatric kidney transplantations with
      deteriorating graft function due to acute rejection refractory to standard
      therapy. Tacrolimus conversion also provides excellent results in the presence of
      cyclosporine toxicity.

PMID- 12185477
TI  - Chronic dialysis in children and adolescents. The 2001 NAPRTCS Annual Report.
AB  - The 2001 annual report of the North American Pediatric Renal Transplant
      Cooperative Study (NAPRTCS) registry includes data on 4,546 dialysis patients.
      Important trends in dialysis care include a significant increase in the use of
      peritoneal dialysis catheters with two cuffs (51.6% vs. 36.2%, P<0.001), a Swan
      neck tunnel (34.1% vs. 20.9%, P<0.001), and a downward pointing exit site (34.9%
      vs. 29.5%, P<0.001) in patients who initiated dialysis between 1997 and 2000
      compared with 1992-1996. Most hemodialysis patients continued to have an external
      percutaneous catheter as their access at the time of initiation of dialysis
      (1,550/1,971 patients, 78.6%), but the odds of using a jugular rather than a
      subclavian vein for these catheters increased by 24% each year between 1992 and
      2000. There was a significant trend for increasing use of erythropoietin and by
      1996, 96% of patients were prescribed this medication at initiation of dialysis.
      There was also a modest, but significant, increase in hematocrit in the dialysis
      registry, as the median hematocrit at 6 months of follow-up was 31% in patients
      who started dialysis between 1997 and 2000 ( P<0.001).

PMID- 12185479
TI  - Long-term survival after post-transplant lymphoproliferative disease in children.
AB  - Post-transplant lymphoproliferative disease (PTLD) is a well-known complication
      of immunosuppressive therapy. We present a series of 19 children who developed
      PTLD, following renal transplantation in 11 and liver transplantation in 8. The
      mean time between transplantation and the onset of PTLD was 19.5 months. Two
      patients had T-cell PTLD and died despite intensive chemotherapy. B-cell PTLD was
      observed in 17 patients and was associated with proven Epstein-Barr virus
      infection in 9. Despite immediate reduction of immunosuppressive therapy, only 8
      of these 17 patients were alive at a 5.6-year mean follow-up. None of these
      patients had recurrence of PTLD when immunosuppression was resumed.

PMID- 12185480
TI  - Surface markers of platelet function in idiopathic nephrotic syndrome in
      children.
AB  - The objective of the study was to investigate platelet activation markers in
      whole blood in idiopathic nephrotic syndrome (INS) in children. The study group
      consisted of 34 children with 45 relapses of INS, 35 children in long-term
      remission of INS, and 26 healthy controls. Using flow cytometry we measured the
      percentage of platelet microparticles, platelet-platelet aggregates, and surface
      expression of CD62P (P-selectin) and CD42b (a component of von Willebrand factor
      receptor). We found an increased percentage of microparticles and platelet
      platelet aggregates, decreased expression of CD42b in the first 2 weeks of INS
      relapse. CD62P expression was elevated only at the onset of INS relapse when
      compared with the long-term remission group and healthy subjects. Children in
      long-term INS remission did not differ from healthy controls. There was no
      significant correlation between platelet activation markers and selected
      biochemical factors of blood in children with INS. Activation of the coagulation
      cascade was confirmed by an elevated serum concentration of F1+2 prothrombin
      fragment during follow-up. These findings suggest that platelets may contribute
      independently to the prothrombotic state in the early stages of INS, but their
      role in triggering relapses remains to be investigated.

PMID- 12185481
TI  - Predictors of peritonitis in children with nephrotic syndrome.
AB  - Patients with nephrotic syndrome (NS) are at increased risk for infection.
      Peritonitis is difficult to diagnose in the absence of peritoneal fluid analysis
      and empiric therapy carries significant risks. We identified factors present at
      initial presentation that are associated with an increased risk for the later
      development of spontaneous bacterial peritonitis in children with NS. A case
      control study of patients admitted to Children's Hospital and Regional Medical
      Center, Seattle from 1989 to 1999 with a diagnosis of NS was conducted; 8 cases
      of NS and peritonitis (aged 20-113 months) and 24 controls with NS alone (aged 10
      193 months) were identified and matched on year of diagnosis of NS. Medical
      charts were reviewed and laboratory values at the time of initial presentation of
      NS were recorded. Odds ratios (OR) were estimated, Fischer's exact test was used
      to obtain P values, and 95% exact confidence intervals (CI) were also calculated.
      Cases tended to be younger than controls (mean age 50.5 months vs. 65.3 months),
      and were more likely to be white and male. There was a suggestion of an
      association between serum albumin level at presentation and the risk of
      subsequent peritonitis. Those patients with a serum albumin level less than or
      equal to 1.5 g/dl at initial presentation were estimated to have a 9.8-fold (95%
      CI 0.93, 472; P=0.06) increase in the odds of developing peritonitis than those
      with an initial albumin greater than 1.5 g/dl. A platelet count greater than 500
      cells/mm(3)tended toward a reduced risk (OR=0.12, 95% CI 0.002,1.29; P=0.10) for
      subsequent peritonitis when compared with patients with a platelet count less
      than 500 cells/mm(3), but was not statistically significant. Hypertension,
      hematuria, or normal serum complement levels (C3, C4) at the time of initial
      diagnosis were not associated with an increased risk of subsequent peritonitis.
      Low serum albumin (< or = 1.5 g/dl) at presentation was associated with an
      increased risk of peritonitis among children with NS at our institution.

PMID- 12185482
TI  - Tubulointerstitial nephritis with uveitis: clinico-pathological and immunological
      study.
AB  - A 10-year-old boy was evaluated for fever, weight loss, uveitis, normocytic,
      normochromic anemia, renal insufficiency, and hypergammaglobulinemia of 8 weeks'
      duration. Infectious and neoplastic causes of fever were excluded. A renal biopsy
      performed in the 4th week of disease revealed diffuse plasmocytic interstitial
      nephritis. No treatment was prescribed and the patient was transferred to another
      hospital. Because clinical symptoms and renal insufficiency were still present,
      in the 8th week of disease a second biopsy was performed, which showed lympho
      monocytic interstitial nephritis. At the same time, phenotypic analysis of
      peripheral blood mononuclear cells was carried out, revealing a significantly
      decreased number of CD3(+), CD4(+), and CD3(+)/CD8(+) cells, increased non-T CD3(
      )/CD8(+) and CD56(+) NK cells, and decreased "naive" (CD45RA(+)/CD4(+)) and
      memory (CD45RO(+)/CD8(+)) T lymphocytes. A 6-month course of oral prednisone was
      prescribed. Clinical symptoms and laboratory findings quickly returned to normal
      values. After 13 days of corticosteroid therapy, a second phenotypic analysis of
      peripheral blood mononuclear cells was performed, which revealed normalization of
      CD3(+), CD4(+), and CD3(+)/CD8(+) cells as well as proportions of non-T CD8(+)
      and CD56(+) NK lymphocytes, "naive" and memory cells. This case shows spontaneous
      evolution of tubulointerstitial infiltrates from plasmacytic to lympho-monocytic,
      profound disturbances of the immunological system, and the beneficial effect of
      corticosteroids on both the clinical course and immunological disturbances.

PMID- 12185483
TI  - Hepatitis B and C virus co-infection in black children with membranous
      nephropathy.
AB  - Membranous glomerulonephritis is a recognized complication of hepatitis B virus
      infection, especially in children, and an occasional complication of hepatitis C
      virus infection. Co-infection with the two viruses has not previously been
      described in membranous glomerulonephritis. We report five black African children
      with membranous glomerulonephritis who were co-infected with hepatitis B and C
      viruses. Proof of hepatitis B virus infection was obtained using serological and
      molecular detection methods. Hepatitis C virus infection was demonstrated using
      reverse transcription to convert viral RNA to cDNA followed by amplification of
      the cDNA using a double round of the polymerase chain reaction with confirmation
      by Southern hybridization and nucleotide sequencing. The clinical, biochemical,
      immunological, and pathological characteristics of the co-infected children, as
      well as the natural history of the disease, did not differ from those in 24
      children with hepatitis B virus-associated membranous glomerulonephritis. Of the
      24 family and household contacts of the five co-infected children, 7 were
      infected with hepatitis B virus, 1 with hepatitis C virus, and none with both
      viruses. It is not known whether infection with the two viruses was acquired
      simultaneously or sequentially. Thus, black children with membranous
      glomerulonephritis are occasionally co-infected with hepatitis B and C viruses.
      The resulting disease appears to be no more severe than that in children infected
      with hepatitis B virus alone.

PMID- 12185484
TI  - The evolution of engrailed genes after duplication and speciation events.
AB  - Members of the engrailed class encode transcription factors involved in major
      steps of metazoan development. Few developmental regulatory genes have been
      studied in such a wide range of animals. Furthermore duplications of an ancestral
      engrailed gene independently generated multiple engrailed paralogues in several
      organisms. This offers the opportunity to reconstruct the evolution of the
      engrailed family and to study the processes involved in the functional
      diversification following speciation or duplication events. The ancestral
      function of engrailedis very likely involved in neurogenesis. Recent studies in
      Drosophila and mice have shown its crucial role in neuronal connectivity and
      neuromuscular targeting. engrailed was probably recruited very early for a role
      in segmentation through intercalary evolution. Several new functions were
      acquired later on in specific phyla. Some duplication events have been followed
      by the loss of one paralogue, whereas others have led to the functional
      diversification of the paralogues. The Duplication-Degenerescence-Complementation
      model recently proposed by Force et al. seems to be the main process involved in
      functional diversification after duplication events. This does not exclude
      acquisition of new functions for one or both paralogues after duplication. The
      acquisition of such new functions principally involves the evolution of cis
      regulatory sequences, but evolution of the coding sequence has also been
      revealed. However, in all engrailed duplications studied, even in ancient
      chromosomal duplications, the paralogues have kept redundant functions. In fact,
      selection seems to maintain a certain redundancy between engrailed paralogues.

PMID- 12185485
TI  - Role of tissue interaction between pineal primordium and neighboring tissues in
      avian pineal morphogenesis studied by intraocular transplantation.
AB  - Tissue interactions play an essential role in organogenesis during embryonic
      development. However, virtually no attempts have been made to study the role of
      tissue interaction in pineal development. In the present study we examined the
      inductive role of the epidermis and mesenchyme in the morphogenesis of quail
      pineal glands. The pineal rudiment is first observed at embryonic day 2 (E2: 2
      days of incubation) at the dorsal midline of the diencephalon as a short semi
      spherical protrusion. Electron microscopic observations revealed that no
      mesenchymal cells are found between the epidermis and the distal end of the E2
      pineal primordium but that a thin layer of mesenchymal cells separate the
      epidermis from the pineal primordium at E3. Small pieces containing pineal
      rudiment were cut off from E2 or E3 embryos. They were treated with enzymes to
      eliminate the epidermis and/or mesenchyme, grafted into E5 chicken eyes, and
      cultured there for 1 week. When E3 pineal rudiment was treated with Dispase to
      remove the epidermis, the pineal gland developed normally. When the rudiment was
      further treated with collagenase to remove the surrounding mesenchymal cells, a
      multi-follicular structure was still formed, but to a lesser extent than when
      rudiments were treated with Dispase alone. When E2 quail pineal rudiment with the
      epidermis was grafted without any treatment, a multi-follicular structure
      developed which morphologically resembled embryonic pineal organs. When the
      epidermis was removed from E2 rudiments by Dispase, a single large vesicular
      structure was formed. These results suggest that the overlying epidermis and/or
      mesenchymal cells play some inductive role in the initial pineal development,
      while the mesenchymal tissue plays an important role in pineal follicular
      formation later during development. Since only a few experimental studies have
      been done to examine pineal morphogenesis, the present study provides fundamental
      insights into avian pineal development.

PMID- 12185486
TI  - Novel and conserved roles for orthodenticle/ otx and orthopedia/ otp orthologs in
      the gastropod mollusc Patella vulgata.
AB  - The orthodenticle/ otx and orthopedia/ otp classes of homeobox gene families have
      been identified in all three major classes of bilaterians: deuterostomes,
      lophotrochozoans, and ecdysozoans. Otx genes have been studied extensively and
      play a role in the development of anterior neural structures. Otp genes have been
      found to be involved in nervous system development in mouse and Drosophila. To
      date, no members of these genes are known in molluscs. We cloned orthologs of
      orthodenticle/ otx and orthopedia/ otpfrom the gastropod Patella vulgata, and
      designated them Pv-otx and Pv-otprespectively. Our analysis of the spatio
      temporal expression pattern of otx and otp orthologs during P. vulgata
      embryogenesis leads to the following conclusions. First, Pv-otx is expressed in
      and around the stomodaeum and our analysis thus supports the previously suggested
      conservation of the protostome and deuterostome larval mouth regions. Second, we
      find that Pv-otp is involved in the development of the larval apical sensory
      organ, suggesting a conserved role for this gene family in nervous system
      development. A similar conserved role in nervous system development has been
      proposed for orthodenticle/otx genes and we suggest that part of the cells
      expressing Pv-otx are involved in the development of the anterior nervous system.
      Last, we postulate that otx genes were ancestrally involved in the development of
      ciliary bands in bilaterians.

PMID- 12185488
TI  - Cloning and expression of a Pitx homeobox gene from the lamprey, a jawless
      vertebrate.
AB  - The Pitx homeobox gene family has important roles in vertebrate pituitary, eye,
      branchial arch, hindlimb and brain development, as well as a key function in
      regulating left-right asymmetry. Here we report the isolation of a Pitx gene,
      PitxA, from two lamprey species, Lampetra planeri and Petromyzon marinus.
      Molecular phylogenetics show PitxA is most closely related to the Pitx1 and Pitx2
      genes of jawed vertebrates, however resolution in the trees is insufficient to
      determine if PitxA is orthologous to a specific jawed vertebrate gene. In situ
      hybridisation studies show lamprey PitxA is expressed in the developing
      nasohypohyseal system and stomodeal ectoderm from early development through to
      early ammocoette larvae. PitxA expression was also detected in several areas of
      the developing brain, in the developing optic system, in pharyngeal endoderm and
      endostyle and in the lateral somite. These results show some key aspects of Pitx
      gene expression in gnathostomes are primitive for all living vertebrates.

PMID- 12185487
TI  - Expression of the ctenophore Brain Factor 1 forkhead gene ortholog (ctenoBF-1)
      mRNA is restricted to the presumptive mouth and feeding apparatus: implications
      for axial organization in the Metazoa.
AB  - Ctenophores are thoroughly modern animals whose ancestors are derived from a
      separate evolutionary branch than that of other eumetazoans. Their major
      longitudinal body axis is the oral-aboral axis. An apical sense organ, called the
      apical organ, is located at the aboral pole and contains a highly innervated
      statocyst and photodetecting cells. The apical organ integrates sensory
      information and controls the locomotory apparatus of ctenophores, the eight
      longitudinal rows of ctene/comb plates. In an effort to understand the
      developmental and evolutionary organization of axial properties of ctenophores we
      have isolated a forkhead gene from the Brain Factor 1 (BF-1) family. This gene,
      ctenoBF-1, is the first full-length nuclear gene reported from ctenophores. This
      makes ctenophores the most basal metazoan (to date) known to express definitive
      forkhead class transcription factors. Orthologs of BF-1 in vertebrates,
      Drosophila, and Caenorhabditis elegans are expressed in anterior neural
      structures. Surprisingly, in situ hybridizations with ctenoBF-1 antisense
      riboprobes show that this gene is not expressed in the apical organ of
      ctenophores. CtenoBF-1 is expressed prior to first cleavage. Transcripts become
      localized to the aboral pole by the 8-cell stage and are inherited by ectodermal
      micromeres generated from this region at the 16- and 32-cell stages. Expression
      in subsets of these cells persists and is seen around the edge of the blastopore
      (presumptive mouth) and in distinct ectodermal regions along the tentacular
      poles. Following gastrulation, stomodeal expression begins to fade and intense
      staining becomes restricted to two distinct domains in each tentacular feeding
      apparatus. We suggest that the apical organ is not homologous to the brain of
      bilaterians but that the oral pole of ctenophores corresponds to the anterior
      pole of bilaterian animals.

PMID- 12185489
TI  - The GEDNAP (German DNA profiling group) blind trial concept.
AB  - This paper presents a review of the organisation and background of blind trial
      systems in general and in particular the system developed in Munster originally
      for the German Society of Forensic Medicine. This system, known as GEDNAP (German
      DNA profiling group), has now evolved into a multinational DNA blind trial open
      to all laboratories involved in paternity and forensic DNA testing.

PMID- 12185490
TI  - Distribution of kerosene components in rats following dermal exposure.
AB  - The systemic distribution of kerosene components in blood and tissues was
      analysed in rats following dermal exposure. Four types of trimethylbenzenes
      (TMBs) and aliphatic hydrocarbons (AHCs) with carbon numbers 9-16 (C(9)-C(16))
      were analysed as major kerosene components by capillary gas chromatography/mass
      spectrometry (GC/MS). The kerosene components were detected in blood and all
      tissues after a small piece of cotton soaked with kerosene was applied to the
      abdominal skin. The amounts of TMBs detected were higher than those of AHCs.
      Greater increases in TMB levels were found in adipose tissue in an exposure
      duration-dependent manner. The amounts of TMBs detected were only at trace levels
      following post-mortem dermal exposure to kerosene. These findings suggest that
      kerosene components were absorbed percutaneously and distributed to various
      organs via the blood circulation. Post-mortem or ante-mortem exposure to kerosene
      could be distinguished when the exposure duration was relatively long. Adipose
      tissue would seem to be the most useful for estimating the degree of kerosene
      exposure.

PMID- 12185491
TI  - HVI and HVII mitochondrial DNA data in Apaches and Navajos.
AB  - Most mtDNA studies on Native Americans have concentrated on hypervariable region
      I (HVI) sequence data. Mitochondrial DNA haplotype data from hypervariable
      regions I and II (HVI and HVII) have been compiled from Apaches (N=180) and
      Navajos (N=146). The inclusion of HVII data increases the amount of information
      that can be obtained from low diversity population groups. Less mtDNA variation
      was observed in the Apaches and Navajos than in major population groups. The
      majority of the mtDNA sequences were observed more than once; only 17.8% (32/180)
      of the Apache sequences and 25.8% of the Navajo sequences were observed once.
      Most of the haplotypes in Apaches and Navajos fall into the A and B haplogroups.
      Although a limited number of haplogroups were observed, both sample populations
      exhibit sufficient variation for forensic mtDNA typing. Genetic diversity was
      0.930 in the Apache sample and 0.963 in the Navajo sample. The random match
      probability was 7.48% in the Apache sample and 4.40% in the Navajo sample. The
      average number of nucleotide differences between individuals in a database is 9.0
      in the Navajo sample and 7.7 in the Apache sample. The data demonstrate that
      mtDNA sequencing can be informative in forensic cases where Native American
      population data are used.

PMID- 12185492
TI  - Post-mortem redistribution of 3,4-methylenedioxymethamphetamine (MDMA, "ecstasy")
      in the rabbit. Part I: experimental approach after in vivo intravenous infusion.
AB  - Post-mortem redistribution is known to influence blood and tissue levels of
      various drugs. An animal model was used in an attempt to elucidate this problem
      for the amphetamine analogue, 3,4-methylenedioxymethamphetamine (MDMA). Rabbits
      received 1 mg/kg MDMA intravenously (iv) and were killed 2 h later in order to
      simulate the state of complete distribution in the body. MDMA and 3,4
      methylenedioxyamphetamine (MDA) concentrations were determined in blood, urine,
      bile, vitreous humour, and various tissues (eye globe walls, brain, cardiac
      muscle, lungs, liver, kidneys, iliopsoas muscle and adipose tissue) using a high
      pressure liquid chromatographic (HPLC) procedure with fluorescence detection. In
      the first group (control group, sampling immediately post mortem) considerable
      MDMA concentrations were found in the brain and both lungs. In addition, our data
      indicate the elimination of MDMA by hepatic biotransformation and excretion via
      the bile. When the animals were preserved either 24 or 72 h post mortem (second
      group), an increase of MDMA and MDA levels in the liver and the eye globe walls
      was noticed. In the lungs, on the other hand, they tended to decline as a
      function of increasing post-mortem interval. MDMA levels in cardiac and iliopsoas
      muscle were fairly comparable and remained stable up to 72 h after death. In the
      third group, ligation of the large vessels around the heart took place
      immediately post mortem, but significant differences in blood and tissue MDMA
      concentrations between rabbits of group 2 and 3 could not be demonstrated. We
      therefore conclude that post-mortem redistribution of MDMA at the cellular level
      (viz. by pure diffusion gradient from higher to lower concentrations) is more
      important than its redistribution via the vascular pathway. Finally, MDA levels
      were relatively low in all samples, thus indicating that this is not a major
      metabolite in the rabbit, at least within the first 2 h after administration.

PMID- 12185493
TI  - Post-mortem redistribution of 3,4-methylenedioxymethamphetamine (MDMA, "ecstasy")
      in the rabbit. Part II: post-mortem infusion in trachea or stomach.
AB  - Drug concentrations in autopsy samples can also be influenced by post-mortem
      gastric diffusion when the stomach contains a substantial amount of the drug or
      by diffusion from the trachea when agonal aspiration or post-mortem regurgitation
      of vomit occurs. This was studied in a rabbit animal model in which MDMA
      solutions were infused post mortem either in the trachea or in the stomach. At
      24, 48 or 72 h post mortem, samples including cardiac blood, vitreous humour,
      urine, bile, gastric content and several tissues were taken for toxicological
      analysis. After post-mortem tracheal infusion, MDMA can easily diffuse not only
      into the lungs but also in great quantities into the cardiac blood and, to a
      lesser extent, into the cardiac muscle. MDMA was also found in the closely
      adjacent diaphragm and in the upper abdominal organs, including the liver and the
      stomach. Following post-mortem infusion into the stomach, considerable MDMA
      levels were found in cardiac blood and muscle, both lungs, diaphragm and liver
      tissue when the solution was concentrated nearby the lower oesophageal sphincter.
      However, when the MDMA solution was present deeper in the stomach, MDMA levels
      were high in the spleen and the liver and relatively low in cardiac blood and
      muscle. In both experiments, MDA levels in most tissues were low or below the
      limit of quantitation, but were substantial in cardiac blood and muscle, lungs
      and diaphragm, indicating that MDMA can be metabolised to MDA after death. These
      results in the rabbit model indicate that the diffusion of MDMA out of the
      stomach content, or due to aspirated vomit and gastro-oesophageal reflux can lead
      to considerable post-mortem redistribution and thus should be taken into account
      in current forensic practice in order to draw the right conclusions when a
      peripheral blood sample is not available.

PMID- 12185494
TI  - Fatal intoxication with omethoate.
AB  - A case of suicide with the insecticide omethoate is reported. An 18-year-old
      apprentice gardener had ingested an unknown amount of omethoate. His body was
      found in his room lying in the storage space under his bed. The autopsy first
      showed multiple superficial incisions in the skin of his wrists, furthermore
      hemorrhagic pulmonary oedema, dilation of the right cardiac ventricle and oedema
      of the brain. The gastric mucosa was swollen and showed a dark brownish colour.
      An intensive, chemical-like smell rose from the corpse and organs. Toxicological
      analysis detected omethoate in cardiac blood (208 micro g/ml), urine (225 micro
      g/ml) and bile (524 micro g/ml), in the liver (341 micro g/ml) and kidneys (505
      micro g/ml). In the gastric content the level was 48223 micro g/ml. The amount of
      the active AChE in peripheral blood serum was reduced to less than 0.2% of the
      normal level. To our knowledge no case of a fatal suicide by ingestion of
      omethoate has been reported in literature.

PMID- 12185495
TI  - D20S161 data for three ethnic populations and forensic validation. Amendment to
      the designation of the STR D20S161 alleles.

PMID- 12185496
TI  - The gene complement for proteolysis in the cyanobacterium Synechocystis sp. PCC
      6803 and Arabidopsis thaliana chloroplasts.
AB  - A set of 62 genes that encode the entire peptidase complement of Synechocystis
      sp. PCC 6803 has been identified in the genome database of that cyanobacterium.
      Sequence comparisons with the Arabidopsis genome uncovered the presumably
      homologous chloroplast components inherited from their cyanobacterial ancestor. A
      systematic gene disruption approach was chosen to individually inactivate, by
      customary transformation strategies, the majority of the cyanobacterial genes
      encoding peptidase subunits that are related to chloroplast enzymes. This allowed
      classification of the peptidases that are required for cell viability or are
      involved in specific stress responses. The comparative analysis between
      Synechocystis and Arabidopsis chloroplast peptidases showed that: (1) homologous
      enzymes that arose by gene duplications in cyanobacteria are functionally diverse
      and frequently do not complement each other, (2) the chloroplast appears to house
      a number of distinct peptidase polypeptide chains of cyanobacterial origin (49)
      which is comparable with a cyanobacterial cell (62) and (3) the peptidase
      complement in plastids results from a combination of the loss of some
      cyanobacterial peptidases and the gain or diversification of subclasses of
      peptidases. This reorganization in the pattern of proteolytic enzymes may reflect
      distinct environmental and physiological changes between prokaryotic and
      organellar systems.

PMID- 12185497
TI  - Maintenance of mitochondrial DNA integrity: repair and degradation.
AB  - Mitochondria have their own genome, which is essential for proper oxidative
      phosphorylation and hence for a large part of ATP production in a cell. Although
      mitochondrial DNA-less (rho(0)) cells can survive under certain conditions, the
      integrity of the mitochondrial genome is critical for the survival of
      multicellular organisms. Mitochondrial DNA (mtDNA) is damaged more than nuclear
      DNA because mitochondria produce a large amount of reactive oxygen species and
      tend to accumulate toxic xenobiotics. Therefore, there is keen interest in
      mechanisms that maintain the integrity of mtDNA. DNA repair may play an important
      role. The repair of mtDNA has been investigated less intensely than nuclear DNA
      repair because, for a long time, it was thought that mitochondria lacked DNA
      repair systems. In fact, DNA damage can be repaired in mitochondria. Base
      excision repair in mitochondria is well established. The enzymes responsible for
      mtDNA repair have been identified and are encoded by the same genes as their
      nuclear counterparts. Mitochondrion-targeting sequences are generated through
      alternative splicing of mRNAs, alternative use of transcription initiation sites,
      or alternative use of translation initiation sites. In addition to DNA repair,
      the degradation of damaged mtDNA may be tolerated because there are multiple
      copies of mtDNA molecules in a cell.

PMID- 12185498
TI  - KNR4 is a member of the PKC1 signalling pathway and genetically interacts with
      BCK2, a gene involved in cell cycle progression in Saccharomyces cerevisiae.
AB  - In budding yeast, PKC1 plays an essential role in cell wall integrity and cell
      proliferation through a bifurcated PKC1/mitogen-activated protein (MAP) kinase
      pathway. The evidence that KNR4 is a member of the PKC1 pathway and genetically
      interacts with BCK2, a gene involved together with Cln3-Cdc28 in the G1 to S
      transition phase of the cell cycle, was as follows. Both KNR4 and BCK2 were
      isolated as a dosage suppressor of a calcofluor white hypersensitive ( cwh43)
      mutant. Overexpression of either of the two genes in a wild-type strain led to
      increased resistance to wall-affecting drugs, while this effect was not obtained
      in a bck2 Delta mutant that overexpressed KNR4. Deletion of KNR4 or BCK2 was
      synthetically lethal with components of the linear PKC1/MAP kinase pathway. Loss
      of Knr4 was lethal in combination with loss of Cln3, as was shown for Bck2. A
      protein interaction between Knr4 and Bck2 was measured using the two-hybrid
      system, although a direct physical interaction could not be detected by co
      immunuprecipation methods. Finally, a genome-wide analysis of cells that
      overexpress BCK2 or KNR4 indicated that both genes also have effects independent
      of each other. In particular, the microarray data showed up-regulation of SWI4,
      which may account for the suppression of the cell lysis of a pkc1 null mutant,
      due to overexpression of BCK2.

PMID- 12185499
TI  - The human minisatellites MS1, MS32, MS205 and CEB1 integrated into the yeast
      genome exhibit different degrees of mitotic instability but are all stabilised by
      RAD27.
AB  - The yeast Rad27 protein is homologous to mammalian Fen1 and is involved in the
      processing of replication intermediates. Enhanced instability of various
      artificial repetitive DNA sequences in RAD27-deficient yeast strains has been
      observed previously and shown to involve preferentially expansion mutations. In
      the present investigation, we characterised the mitotic instability of alleles of
      the naturally occurring human minisatellites MS1, MS32, MS205 and CEB1 and the
      modified MS1 alleles containing more highly homogeneous repeat regions than the
      original alleles. These minisatellites demonstrated more pronounced instability
      in rad27 Delta strains, with increases in the frequencies of both expansion and
      contraction mutants. In RAD27 strains, MS32 and MS205 were relatively stable,
      while MS1 and CEB1 were unstable, indicating that the effect of RAD27 on
      stability is influenced by intrinsic properties of the repeat array. This
      conclusion received further support from the remarkably high frequency of length
      mutants observed for the modified allele of MS1. Thus, our findings emphasise the
      importance of: (1) comparing results obtained with various naturally occurring
      minisatellites and (2) manipulating their sequences in attempts to understand the
      molecular basis for mitotic stability/instability of minisatellite DNA.

PMID- 12185500
TI  - Fission yeast Cdc23 interactions with DNA replication initiation proteins.
AB  - Schizosaccharomyces pombe Cdc23 is an essential DNA replication protein,
      conserved in eukaryotes and functionally homologous with Saccharomyces cerevisiae
      Dna43 (Mcm10). We sought evidence for interactions between Cdc23 and the MCM2-7
      complex, a component of both the pre-replicative complex and the replication
      fork. Cdc23 shows genetic interactions with four MCM subunits: cdc23-M36 and
      cdc23-1E2 alleles both show synthetic phenotypes with mcm2 (cdc19-P1) and mcm6
      (mis5-268), and cdc23-M36 is synthetically lethal with mcm4 (cdc21-K46) and with
      mcm5 (nda4-108). The wild-type cdc23 gene on multicopy plasmids can partially
      suppress temperature-dependent defects in mcm5 (nda4-108). Two-hybrid analysis
      demonstrates interactions at the protein-protein level between Cdc23 and Mcm4,
      Mcm5 and Mcm6. Cdc23 also interacts with four subunits of the Schizosaccharomyces
      pombe origin recognition complex (ORC) in yeast two-hybrid assay: Orc1, Orc2,
      Orc5 and Orc6. We found no evidence for interaction between Cdc23 and the MCM
      recruitment factor Cdc18 (the homologue of Saccharomyces cerevisiae Cdc6). Unlike
      Cdc18, Cdc23 mRNA shows no significant fluctuation in level through the cell
      cycle. These data suggest that fission yeast Cdc23 is an MCM-associated factor
      which has a role in the initiation of DNA replication.

PMID- 12185501
TI  - Structural and functional characterization of a transcription-enhancing sequence
      element in the rbcL gene of the Chlamydomonas chloroplast genome.
AB  - The structure and function of a transcription-enhancing sequence element in the
      coding region of the Chlamydomonas reinhardtii rbcL gene was analyzed in
      Chlamydomonas chloroplast transformants in vivo. The enhancer sequence is
      contained within a DNA segment extending from position +108 to position +143,
      relative to the start site of rbcL gene transcription. The sequence remains
      functional when inverted or when placed 34 bp closer to or 87 bp further
      downstream of the basic rbcL promoter. However, it does not function from a site
      about 250 bp downstream of its original location. Besides promoting transcription
      initiation from the rbcL promoter, the element is able to augment transcription
      from the promoter of the Chlamydomonas chloroplast atpB gene, but has an
      inhibitory effect on transcription from the promoter of the chloroplast ribosomal
      RNA genes. The results suggest that the enhancer-like sequence acts upon
      transcription initiation in a position-specific and promoter type-specific
      manner.

PMID- 12185502
TI  - A chimeric open reading frame associated with cytoplasmic male sterility in
      alloplasmic wheat with Triticum timopheevi mitochondria is present in several
      Triticum and Aegilops species, barley, and rye.
AB  - Mitochondrial DNA from Triticum timopheevi has a chimeric gene, orf256, upstream
      of coxI. This gene is cotranscribed with coxI in cytoplasmic male sterile plants
      and produces a 7-kDa protein which is not produced in fertile or fertility
      restored plants. T. aestivum, the nuclear donor in sterile plants, does not have
      orf256. Analysis by polymerase chain reaction of DNA from barley, rye, Aegilops
      bicornis, Ae. searsii, Ae. sharonensis, Ae. speltoides, Ae. tauschii, T.
      monococcum, and T. turgidum was done with oligonucleotide primers designed to
      detect orf256 or coxI sequences. Except for T. turgidum, these plants have
      various elements of the orf256 sequence over a 1-kb length of DNA immediately
      upstream of coxI in exactly the same arrangement as is found in the coxI region
      of T. timopheevi. Only T. timopheevi and Ae. speltoides have orf256 transcripts,
      and only cytoplasmic male-sterile plants involving these two species as maternal
      donors produce a protein from orf256. Part of an orf256-like sequence is present
      in T. turgidum but is at least slightly different in arrangement relative to
      coxI, as compared with the sequence in T. timopheevi. Neither maize nor sorghum
      have the orf256 sequence.

PMID- 12185503
TI  - Incidence and evolution of monoclonal gammopathy of undetermined significance
      (MGUS) in Greece.
AB  - Monoclonal gammopathy of undetermined significance (MGUS) is a relatively common
      condition among individuals older than 70 years. The actuarial risk of MGUS
      progression to an overt plasma cell malignancy (PCM) after 20 years of follow-up
      has been reported to be as high as 30%. The purpose of this study was to evaluate
      the incidence and evolution of MGUS in a Greek population: 1564 consecutive
      patients older than 50 years who were admitted to the Department of Clinical
      Therapeutics at the University of Athens School of Medicine for various reasons
      over a 26-month period were evaluated with serum protein electrophoresis. In
      cases in which a monoclonal protein was detected, a panel of tests was performed
      to rule out an underlying plasma cell malignancy (PCM). Serum levels of
      interleukin (IL)-6, IL-6-soluble receptor (IL-6SR), IL-1 beta, and transforming
      growth factor beta 1 were also measured in the MGUS cases. Patients with MGUS
      were monitored at regular intervals for evidence of multiple myeloma or other
      PCMs. The incidence of MGUS was 4% and there was a positive correlation with
      increasing age. The median value of serum M peak was only 5.3 g/l. After a median
      follow-up of 71 months, only two patients developed multiple myeloma (60 and 75
      months after initial diagnosis). Our data are consistent with those of other
      epidemiological studies regarding the incidence of MGUS, but the monoclonal
      protein levels and the probability of evolution to a malignant plasma cell
      disorder appeared to be lower in our study than in other series. Our data support
      the hypothesis that individuals with low M peak values require only regular
      annual follow-up examinations.

PMID- 12185504
TI  - Intermediate doses of melphalan and dexamethasone are better than vincristine,
      adriamycin, and dexamethasone (VAD) and polychemotherapy for the treatment of
      primary plasma cell leukemia.
AB  - Primary plasma cell leukemia (PPCL) is a rare form of disease accounting for 1-2
      percent of myelomas. Between September 1990 and November 2000, among 540 patients
      with myeloma studied, 24 fulfilled the criteria of PPCL (4.4 percent). We found
      high frequencies of female patients (62 percent), Bence Jones proteinuria (79
      percent), anemia (88 percent), bleeding (54 percent), confusional syndrome (42
      percent), weight loss (71 percent), hepatomegaly (25 percent), splenomegaly (21
      percent), leukocytosis (62 percent), and thrombocytopenia (71 percent). High
      serum levels of creatinine, calcium, lactate dehydrogenase (LDH), and beta(2)
      microglobulin were detected in 50 percent, 37 percent, 58 percent, and 71
      percent, respectively. Four patients were treated with vincristine, melphalan,
      cyclophosphamide, prednisone, and adriamycin (VMCPA), 12 with vincristine,
      adriamycin, and dexamethasone (VAD), and 8 with M-80 (oral melphalan 80 mg/m(2)
      plus dexamethasone 40 mg/m(2)). There was a trend toward lower values of
      Karnofsky score (P=0.07) and higher values of LDH (P=0.2) in the VAD group. Other
      clinical characteristics were comparable among the three groups. Complete plus
      partial responses were achieved in one and six patients treated with VMCPA and M
      80, respectively. All patients treated with VAD failed to respond to treatment.
      Patients receiving the M-80 regimen experienced higher platelet toxicity
      (P=0.05), vomiting (P<0.0003), and mucositis. Also, the need for red blood cell
      transfusions was higher in the M-80 group. Median overall survival was 60 days.
      Overall survival was better in patients achieving complete or partial response.
      In conclusion, our study illustrates that intermediate doses of melphalan plus
      dexamethasone are an effective chemotherapy regimen for this aggressive disease.
      Response to treatment is the only prognostic factor for survival in these
      patients.

PMID- 12185505
TI  - Combined therapy in the treatment of primary mediastinal B-cell lymphoma:
      conventional versus escalated chemotherapy.
AB  - Treatment of patients with primary mediastinal B-cell lymphoma (PMBCL) remains
      controversial. We started a controlled clinical trial to evaluate the efficacy
      and toxicity of a conventional versus more intensive regimen of combined
      chemotherapy followed by radiotherapy to the mediastinum with the mantle
      technique. From 1989 to 1997, 68 patients diagnosed with previously untreated
      PMBCL, aged 18-65 years and negative for immunodeficiency virus test, were
      considered candidates to receive either conventional chemotherapy with CEOP-Bleo
      (cyclophosphamide 750 mg/m(2), vincristine 1.4 mg/m(2), prednisone 40 mg/m(2),
      epirubicin 70 mg/m(2), and bleomycin 10 mg/m(2)) or mega CEOP-Bleo
      (cyclophosphamide 1000 mg/m(2), epirubicin 120 mg/m(2), vincristine, prednisone,
      and bleomycin at the same doses) every 21 days for six cycles, followed by
      radiotherapy to the mediastinum with the mantle technique (35-45 Gy, mean 38 Gy).
      Complete response (CR) rates were not statistically different: 64% [95 percent
      confidence interval (CI): 58 percent to 70 percent] for conventional arm vs 81
      percent (95 CI: 77-86 percent) in the intensive group (p=0.2). However, failure
      free survival (FFS) and overall survival (OS) had statistical differences. At 5
      years, actuarial FFS for patients treated with conventional chemotherapy was 51
      percent (95 percent CI: 44-59 percent) compared to 70 percent (95 percent CI: 65
      76 percent) in the intensive arm (p>0.01). OS rates were also different: 54
      percent (95 percent CI: 48-57 percent) vs 70 percent (95 percent CI: 65-76
      percent), respectively (p<0.01). Toxicity was mild and no therapy-related deaths
      were observed. At a median follow-up of 7.3 years, no second neoplasia or acute
      leukemia has been observed. The international prognostic index was not useful to
      define clinical risk in this selected group of patients. Multivariate analysis
      identified pleural and pericardial effusion and chemotherapy regimen as
      prognostic factors influencing FFS and OS. We feel that patients with PMBCL
      should be treated with more intensive, but not myeloablative chemotherapy,
      followed by adjuvant radiotherapy to achieve an improvement in outcome in this
      setting of patients. Patients with pleural or pericardial effusion are considered
      at high risk for failure with the actual programs of treatment and probably will
      be considered for experimental therapeutic approaches.

PMID- 12185506
TI  - Infectious complications after autologous hematopoietic stem cell
      transplantation: comparison of patients with acute myeloid leukemia, malignant
      lymphoma, and multiple myeloma.
AB  - It is yet undetermined whether patients with different hematological malignancies
      have different propensities to infectious complications after high-dose
      chemotherapy (HDC) and autologous hematopoietic stem cell transplantation (HSCT).
      We retrospectively analyzed 136 cycles of HDC and autologous HSCT in 114 patients
      with acute myeloid leukemia (AML, 24 cycles), non-Hodgkin's lymphoma/Hodgkin's
      disease (NHL/HD, 55 cycles), and multiple myeloma (MM, 57 cycles) with respect to
      early infectious complications. Median duration of neutropenia was longer in
      patients with AML and NHL/HD than in patients with MM (11 days vs 8 days) and
      after conditioning including total body irradiation (TBI) compared with
      chemotherapy only preparative regimens (11 days vs 7 days). Fever requiring
      antimicrobial therapy was observed in 88 percent of cycles, with fever of unknown
      origin (FUO) accounting for 60 percent of febrile episodes. There was no proven
      fungal infection, but one case of probable invasive pulmonary aspergillosis.
      Microbiologically documented infections were seen in 29 percent and clinically
      documented infections in 11 percent. Response to first-line empirical antibiotic
      therapy was better for FUO than for documented infections (70 percent vs 40
      percent). Patients with TBI as part of their conditioning regimen had more
      overall infections than patients without TBI (96 percent vs 82 percent). There
      were no differences with respect to the type or incidence of infections between
      patients with AML, NHL/HD, and MM. Patients with different hematological
      malignancies have similar rates of early infectious complications after HDC and
      autologous HSCT. TBI may be associated with an increased risk for infections in
      the early post-transplant period.

PMID- 12185507
TI  - Autologous recovery following non-myeloablative unrelated donor bone marrow
      transplantation for severe aplastic anaemia.
AB  - We report the outcome of nine unrelated bone marrow transplants performed for
      acquired severe aplastic anaemia at a single centre. Six patients received
      transplants from fully matched donors. Three donor/recipient pairs were
      mismatched, two at a single allele on high resolution typing. Pre-transplant
      conditioning consisted of cyclophosphamide and in vivo Campath-1 monoclonal
      antibody. One patient also received total body irradiation (TBI), and another
      patient with a coexisting paroxysmal nocturnal haemoglobinuria (PNH) clone
      received additional busulphan. Cyclosporin A was given for 12 months as
      prophylaxis against graft-versus-host disease (GVHD). Six of nine patients are
      alive and transfusion independent with a mean follow-up of 24 months (range: 1.5
      94). All six patients who received fully matched transplants are alive; the three
      who received mismatched grafts died. Four long-term survivors developed
      autologous haematological recovery following rejection of their grafts. Acute
      GVHD grade II+ occurred in two patients. We highlight the importance of high
      resolution HLA typing, including Cw matching in reducing the incidence of graft
      rejection and GVHD, resulting in improved survival in our patient group. This
      study also shows that autologous recovery with long-term survival can occur
      following non-irradiation conditioning regimens.

PMID- 12185508
TI  - Soluble tumor necrosis factor receptor type II in the early diagnosis of fever in
      neutropenia.
AB  - Sepsis in chemotherapy-associated neutropenia is a major cause of mortality in
      the treatment of acute myeloid leukemia (AML). Early diagnosis of sepsis is
      crucial for patient survival. We analyzed the value of prospectively measuring
      serum concentrations of soluble tumor necrosis factor receptor type II (sTNF-RII)
      in patients with AML for early diagnosis of sepsis in neutropenia. Therefore, 54
      adult patients with AML and neutropenia were followed around the onset of fever.
      A total of 59 febrile episodes were documented. We could not demonstrate a
      significant increase in sTNF-RII levels prior to fever. sTNF-RII concentrations
      were not predictive of the severity of a febrile episode. Based on these data, we
      cannot recommend the routine screening of sTNF-RII for early detection of septic
      complications in patients undergoing cytoreductive therapy of AML.

PMID- 12185509
TI  - Hemoglobin A2' (HbA2delta') in the Mauritanian population: first results of a
      preliminary survey.
AB  - The Mauritanian population consists of two main groups: one Arab and Berber
      population and one of Black African origin. The latter includes five ethnic
      groups: Pular, Soninke, Black Maurs, Wolof, and Bambara. Abnormal HbA2 was found
      in the Mauritanian population and was characterized by cellulose acetate
      electrophoresis at pH 8.4 followed by DNA analysis. Among 785 subjects examined,
      17 were carriers of HbA2' corresponding to 2.16 percent. The highest frequency
      was observed among the Pular (3.09 percent), the Black Maurs (2.72 percent), the
      Wolof (2.27 percent), and the Soninke (2.04 percent).

PMID- 12185510
TI  - Compound heterozygosity for Hb Korle-Bu (beta(73); Asp-Asn) and Hb E (beta(26);
      Glu-Lys) with a 3.7-kb deletional alpha-thalassemia in Thai patients.
AB  - Hemoglobin (Hb) Korle-Bu (beta73; Asp-Asn) is the most frequent of the rare beta
      chain variants in the population of West Africa whereas Hb E (beta26; Glu-Lys) is
      common among the Southeast Asian population. We report a hitherto undescribed
      condition in which these two beta-chain variants co-segregate. The proband was a
      19-year-old Thai pregnant woman in her second trimester of pregnancy who visited
      our thalassemia screening unit. Cellulose acetate electrophoresis and high
      performance liquid chromatography (HPLC) analysis of Hb detected one abnormal Hb
      in addition to the Hb E. Analysis of DNA sequences revealed a GAT-AAT mutation at
      codon 73 in trans to a GAG-AAG mutation at codon 26 of the beta-globin gene.
      Polymerase chain reaction (PCR) analysis of the alpha-globin gene cluster of the
      patient detected a 3.7-kb deletional alpha-thalassemia 2. Family study identified
      that her mother had the same genotype and her father was a simple Hb E carrier.
      The hematological data of these unusual cases of hemoglobinopathy are presented
      and compared with a simple heterozygote for Hb Korle-Bu found in another
      unrelated Thai family. beta-Globin gene haplotype linked to the Thai beta(Korle
      Bu) and a simple DNA assay based on allele-specific PCR for rapid diagnosis of Hb
      Korle-Bu are also described.

PMID- 12185511
TI  - Massive postoperative intramuscular bleeding in acquired von Willebrand's
      disease.
AB  - We describe a case of acquired von Willebrand's disease (vWD) associated with
      monoclonal gammopathy with undetermined significance (MGUS) in a 54-year-old man
      who was admitted with hemarthrosis and extensive thigh muscle hematoma following
      arthroscopic surgery and postoperative prophylaxis with low molecular weight
      heparin. Coagulation tests were compatible with acquired vWD: prolonged activated
      partial thromboplastin time (aPTT) (56.1 s), decreased levels of factor VIII
      coagulant activity (23%), low concentrations of von Willebrand's factor (vWF)
      antigen (13%), and undetectable ristocetin cofactor activity (<10%). Infusion of
      a vWF-containing factor VIII concentrate failed to normalize the plasma levels of
      vWF-related parameters. Only additional intravenous administration of
      immunoglobulins led to a transient normalization of ristocetin cofactor activity,
      vWF antigen, and factor VIII coagulant activity. While the spontaneous bleeding
      tendency in this case was mild, surgery and administration of prophylactic doses
      of low molecular weight heparin led to life-threatening bleeding.

PMID- 12185513
TI  - Localized Castleman's disease and nephrotic syndrome not responsive to resection
      plus colchicine therapy.
AB  - We describe one patient with localized Castleman's disease (CD) of the mixed
      hyaline vascular and plasma cell type located at the mesentery of the small
      bowel, associated with systemic amyloidosis and nephrotic syndrome. A true
      nephrotic syndrome has rarely been reported in patients with CD. In the
      literature, it has been suggested that clinical and laboratory manifestations
      generally improved after surgical resection of the tumor. However, in our case,
      clinical and laboratory findings did not regress after operation followed by
      colchicine therapy.

PMID- 12185512
TI  - A Sweet-like syndrome manifesting as gingival hyperplasia and myositis without
      cutaneous involvement.
AB  - Sweet's syndrome or acute febrile neutrophilic dermatosis, characterized by
      fever, neutrophilia, and focal infiltration of the dermis was originally
      described after episodes of infection. It is also known to occur in acute myeloid
      leukemia. A patient with acute myeloid leukemia (AML M3) developed gingival
      hyperplasia and muscle swelling and tenderness after starting treatment with all-
      trans retinoic acid. Microscopic examination showed neutrophilic infiltrate. All
      cultures were sterile. The lesions did not respond to cytotoxic therapy and
      continued to persist even after achievement of remission. The response was seen
      only after prednisolone was started. This case highlights the fact that a Sweet
      like syndrome can occur without the characteristic cutaneous lesions and in such
      situations there can be considerable diagnostic and therapeutic difficulty.

PMID- 12185514
TI  - Chronic lymphocytic leukemia presenting with symptomatic central nervous system
      involvement.
AB  - Leukemic infiltration of the central nervous system (CNS) resulting in
      neurological manifestations is a rare complication of chronic lymphocytic
      leukemia (CLL). Furthermore, symptomatic CNS involvement as the initial
      presentation of previously undiagnosed CLL is extremely rare. In the present
      report, the authors describe a case of an 89-year-old female previously diagnosed
      with Alzheimer's disease who suddenly developed rapidly worsening mental changes.
      Cytological and immunocytological examinations of the lymphoid cells present on
      the cerebrospinal fluid (CSF) revealed CNS involvement by a clonal B-cell
      lymphoproliferative disorder, most consistent with de novo B-CLL expressing kappa
      light chain restriction. Subsequently, flow cytometric analysis done on the
      peripheral blood lymphocytes confirmed the diagnosis of B-CLL in this patient.
      Thus, this study shows the potential usefulness of immunocytological evaluation
      in detecting monoclonal lymphoid populations on CSF samples in adult patients
      presenting with altered mental status and CSF pleocytosis of lymphocytes.

PMID- 12185515
TI  - Intraperitoneal rituximab: an effective measure to control recurrent abdominal
      ascites due to non-Hodgkin's lymphoma.
AB  - We report a patient with an advanced stage low-grade small lymphocytic lymphoma
      who required regular drainage of malignant ascites for symptomatic relief despite
      intensive treatment. The administration of rituximab via the intraperitoneal
      route successfully controlled the ascites. The patient tolerated well with this
      unusual route of administration and has not required any further ascitic drainage
      for at least 8 months. In view of its simplicity, good tolerability and
      effectiveness to control recurrent ascites secondary to low-grade non-Hodgkin's
      lymphoma (NHL), this novel route of administration of rituximab is worth
      exploring.

PMID- 12185516
TI  - Severe regimen-related toxicity occurring in a patient with XYY syndrome
      receiving allogeneic peripheral blood stem cell transplantation.
AB  - A 23-year-old man with chronic myelocytic leukemia (CML) in the first chronic
      phase underwent allogeneic peripheral blood stem cell transplantation (PBSCT)
      from his HLA-identical sibling. Pretransplant evaluations showed that he had a
      low risk of transplantation-related mortality and that the interval between the
      diagnosis of CML and PBSCT was only 6 months. However, he developed a variety of
      complications, including acute renal failure requiring hemodialysis, severe
      hepatic damage, hemorrhagic cystitis, and gastrointestinal hemorrhage leading to
      hypovolemic shock. Pathological examination of the colonic mucosa showed vascular
      endothelial damage and thrombotic lesions, leading to the diagnosis of thrombotic
      microangiopathy. Later, we found that he had the constitutional abnormality XYY.
      XYY syndrome is a frequent congenital abnormality, and mental disorders and
      congenital abnormalities of kidney and liver are common manifestations.
      Considering his clinical course, it was interesting that complications were
      severe in the organs which are frequently involved in cases of XYY syndrome.
      These organs may have poor function or poor reserves and may be more vulnerable
      to endothelial damage caused by high-dose cytotoxic chemotherapy. Patients with
      XYY syndrome might have a high risk of transplantation-related mortality.

PMID- 12185517
TI  - Nonmyeloablative allogeneic stem cell transplantation for refractory Hodgkin's
      lymphoma complicated by interleukin-2 responsive progressive multifocal
      leukoencephalopathy.
AB  - Nonmyeloablative allogeneic stem cell transplantation (NMASCT) can be used to
      exploit the graft-versus-tumor (GVT) potential of allogeneic donor cells in the
      setting of reduced conditioning regimen toxicity. This approach is particularly
      attractive for patients who have received extensive prior therapy and are poor
      candidates for traditional allogeneic stem cell transplantation. However,
      toxicity in heavily pretreated patients remains uncertain. Additional
      immunosuppression in already immunocompromised patients may result in unexpected
      toxicity. We report a case of probable progressive multifocal leukoencephalopathy
      (PML) responsive to interleukin-2 (IL-2) following a NMASCT in a 29-year-old
      woman with relapsed Hodgkin's lymphoma. The patient developed severe neurological
      symptoms approximately 6 weeks following NMASCT associated with low CD4+ cell
      counts and magnetic resonance imaging (MRI) was consistent with PML. IL-2 therapy
      resulted in increasing CD4+ counts and progressive resolution of neurological
      symptoms. Disruption of IL-2 therapy led to neurological deterioration, which
      responded to reinstitution of IL-2 therapy. The patient's lymphoma initially
      progressed following NMASCT, but has responded to donor leukocyte infusions
      (DLI). This case reiterates the potent GVT potential of NMASCT in patients with
      Hodgkin's disease. However, it demonstrates the potential for severe
      complications related to immunosuppression, especially in heavily pretreated
      patients. The toxicity after NMASCT should not be understated and will need to be
      explored further.

PMID- 12185518
TI  - Advances in bone tumour treatment in 30 years with respect to survival and limb
      salvage. A single institution experience.
AB  - We analysed 721 patients with primary malignant bone tumours treated in a single
      institution with regard to diagnosis, treatment and prognosis. From 1965 to 1974,
      154 patients were treated, of whom 17% had no surgery, 36% underwent resection
      and 46% underwent amputation. Margins of resection were intralesional in 21%, 72%
      of patients received chemotherapy and overall survival rate was 24%. From 1975 to
      1984, 174 patients were treated, of whom 12% had no surgery, 54% underwent limb
      salvage procedures and 34% underwent amputation or resection-replantation.
      Margins of resection were intralesional in 16% 67% of patients received
      chemotherapy and overall survival rate was 46%. From 1985 to 1994, 393 patients
      were treated, of whom 7% had no surgery, 77% underwent limb salvage procedures -
      mainly with endoprostheses - and 15% underwent amputation or resection
      replantation. Margins of resection were intralesional in 12%, 68% of patients
      received chemotherapy and overall survival rate was 62%. Advancements in the
      treatment of primary malignant bone tumours justify limb salvage procedures in
      combination with highly effective polychemotherapy in specialised centres and has
      resulted in an overall survival rate of more than 60%.

PMID- 12185519
TI  - Bone substitutes as carriers for transforming growth factor-beta(1) (TGF
      beta(1)).
AB  - We studied the suitability of three different hydroxyapatite materials (Endobone,
      Bio-Oss and Algipore) as carriers for the bone growth promoting factor TGF
      beta(1). The hydroxyapatite materials either were incubated for 24 h or directly
      loaded with hrTGF-beta(1) (Diagnostic Products Corporation, DPC) at a
      concentration of 10 ng hrTGF-beta(1)/mg. For the release experiment the
      hydroxyapatite materials covered with hrTGF-beta(1) were either suspended in pure
      phosphate buffered saline (PBS) or human serum albumin (HSA). The concentration
      of hrTGF-beta(1) was measured every 6 h the first day and then daily at the 2nd,
      7th, 14th and 28th day. With Bio-Oss and Endobone the release of growth factor in
      HSA showed a two-phase kinetics. TGF-beta(1) reached a maximum concentration
      within the first 24 h and decreased almost linearly until day 28. With Algipore
      the concentration of growth factor reached a maximum after 12 h and showed a
      rapid decline until day 2. From day 2 the TGF-beta(1) concentrations remained
      low. Significantly, more TGF-beta(1) was released into HSA than into PBS. Our
      study suggests that the hydroxyapatite materials are suitable as TGF-beta(1)
      carriers.

PMID- 12185520
TI  - Surgical treatment of adult idiopathic scoliosis - comparison of two
      instrumentations.
AB  - In this study, 22 women patients with adult idiopathic scoliosis treated
      surgically with Cotrel-Dubousset instrumentation (CDI) or Texas Scottish Rite
      Hospital instrumentation (TSRHI) were followed up for 56.2+/-4.0 months. The
      overall immediate and final corrections were respectively 21.5+/-40 (58%) and
      26.6+/-2.90 (48%), giving a loss of correction of 5.1+/-1.00 (10%). No
      significant differences were found in these two parameters between the two
      groups. The functional outcomes were good in 21 patients. There was no difference
      between CDI and TSRHI in deformity correction.

PMID- 12185521
TI  - Intramedullary nailing of humeral shaft fractures.
AB  - From 1996 until 2000 we treated 52 humeral shaft fractures with AO unreamed
      nailing. Mean patient age was 35.8 years and the average follow-up 29.6 months.
      There were 31 type A fractures, 15 type B, and 6 type C. Closed retrograde
      nailing was performed in 46 cases and open nailing in six. Functional results
      were excellent in 48 cases, moderate in three, and poor in one.

PMID- 12185523
TI  - Arthroscopy of the elbow joint-video analysis of the anatomy and function.
AB  - The anatomical structures of the elbow joint were dissected in layers in human
      cadavers. The surgical dissection was divided into to deep and superficial areas.
      Each step was documented by digital video and photographs. The functional and
      anatomical preparation allowed us to establish the limits and scope of diagnostic
      and therapeutic procedures by arthroscopy.

PMID- 12185522
TI  - Non-union of the humeral shaft treated by internal fixation.
AB  - We reviewed 40 cases with non-union of the humeral shaft. There were 31 men and
      nine women patients with an average age of 38.5 (35-65) years. Thirty-four non
      unions were of the atrophic type. Non-union was most often found at the
      transition of the middle third to the lower third of the humeral shaft. Six
      fractures were classified as open at the time of the initial injury. All patients
      were treated by open reduction and internal fixation with a dynamic compression
      plate (DCP). Cancellous bone graft was used in all atrophic non-unions. In one
      patient an additional fibular graft was used. The average follow-up was 13 (6-18)
      months. Final results were available for 34 patients. Thirty-one fractures (91%)
      healed in an average of 4.5 (3-9) months. Main complications were temporary
      radial nerve palsy in two patients and deep infection in one.

PMID- 12185524
TI  - Hip fractures in Hungary and Sweden - differences in treatment and
      rehabilitation.
AB  - Data of 1,337 consecutive hip fracture patients were registered during 1 year
      within a prospective comparative multicenter study comparing osteosynthesis
      techniques and rehabilitation results in Budapest, Hungary, in Sundsvall,
      northern Sweden, and in Lund, southern Sweden. In Budapest the mean age was 4-5
      years lower than in Sweden, and more patients lived in their own home (91% versus
      70% and 62%). Less intracapsular (41% versus 54% and 54%) and more trochanteric
      fractures (52% versus 40% and 35%) were observed in Budapest. Many more Hungarian
      patients returned home (68% versus 54% and 33%); however, their mortality rate 4
      months later significantly exceeded that of the Swedish centres (24% versus 15%
      and 13%), and more had severe pain in the operated hip (27% versus 17% and 15%).
      Four months after double nail osteosynthesis of displaced cervical fractures,
      more patients (28%) had severe hip pain than after hemiarthroplasty (16%) in
      Budapest as compared to Lund or Sundsvall (19% and 22%). Mortality rate after 4
      months following hemiarthroplasty and nailing (36% and 20%) was significantly
      higher than in the Swedish centres (14% and 11%).

PMID- 12185525
TI  - Cemented or uncemented hemiarthroplasty for displaced intracapsular femoral neck
      fractures.
AB  - The aim of this study was to establish whether or not to cement the
      hemiarthroplasty for displaced intracapsular femoral neck fractures in the
      elderly. Consecutive patients treated by hemiarthroplasty in adjacent hospitals
      were reviewed. The same monoblock prosthesis was used; in hospital A they were
      uncemented (121 patients), and in hospital B they were cemented (123 patients).
      Notes were reviewed retrospectively. Surviving patients (50 and 56 respectively)
      were assessed prospectively for pain and functional ability using validated
      scoring systems. Follow-up was 32-36 months. Patient demographics were similar.
      Fewer of the cemented group had been revised or were awaiting revision (
      P=0.036). There was no difference in general complication or mortality rates.
      There was a highly statistically significant greater deterioration in pain (
      P=0.003), walking ability ( P=0.002), use of walking aids ( P=0.003) and
      activities of daily living ( P=0.009) in the uncemented group. Our findings
      support the use of cemented hemiarthroplasty in the elderly.

PMID- 12185526
TI  - Primary bipolar hemiprosthesis for unstable intertrochanteric fractures.
AB  - Between 1997 and 2001 we treated 54 elderly patients with unstable
      intertrochanteric fractures by primary hemiarthroplasty using a cemented bipolar
      prosthesis. Mean patient age was 75.6 (64-91) years and mean follow-up was 22.3
      (5-48) months. Seven patients died before the fourth post-operative month. Thirty
      three patients were able to walk with a walker in the first post-operative week.
      There were no dislocations or aseptic loosening. One deep infection was
      encountered after 1 year. Acetabular erosion was seen in one patient and non
      union of the greater trochanter was seen in four. Five patients experienced leg
      length discrepancy. We obtained 17 excellent and 14 good results after 12 months
      according to the Harris hip-scoring system. We observed that the inner motion of
      the bipolar head decreased over time.

PMID- 12185527
TI  - Intertrochanteric osteotomy for osteonecrosis of the femoral head.
AB  - We studied 32 hips (in 27 patients) treated by intertrochanteric osteotomy for
      osteonecrosis of the femoral head. Average follow-up was 17 (range 9-26) years.
      There were 22 men and 5 women with an average age of 39 (range 25-55) years.
      Eleven hips were classified as Ficat stage II, 19 as stage III and two as early
      stage IV. Nine hips showed collapse of the femoral head within 3 years after
      operation and in six hips collapse occurred after 3-8 years. In 13 hips slow
      progression with incipient signs of arthrosis was noted 8 years after surgery.
      Four hips with a moderate degree of necrosis at the time of surgery showed no
      radiological progression 9-26 years after operation. We recommend
      intertrochanteric osteotomy for patients with Ficat stage II and early stage III,
      provided that they still have a good range of motion in the hip.

PMID- 12185528
TI  - Isoelastic femoral component in primary cementless total hip arthroplasty.
AB  - We followed 100 patients (111 hips) who underwent primary total hip arthroplasty
      between July 1988 and June 1995 using the isoelastic femoral component. The
      average age was 61 (30-70) years. Mean follow-up time was 8.4 (5-12) years. Three
      femoral components were revised for aseptic loosening and one for disabling thigh
      pain. Six additional femoral components were considered probably loose by the
      radiographic criteria. Osteolysis around the femoral component was noted in only
      two patients who were clinically asymptomatic. A high incidence (41%) of lateral
      migration of the tip of the femoral components was noted, but there was no
      significant distal migration. Nine patients complained of thigh pain, which
      interfered with their daily activities. The average Harris hip score improved
      from 49 to 80 at the latest follow-up. We believe that the principle of
      isoelasticity in hip replacement is important; however, improvements in the
      material and the design of the femoral component are required.

PMID- 12185529
TI  - Biodegradable arrows for arthroscopic repair of meniscal tears.
AB  - Thirty-two meniscal tears in 32 patients were repaired using biodegradable
      meniscus arrows. The tears were fixed arthroscopically using an all-inside
      technique. Ten patients had a simultaneous anterior cruciate ligament (ACL)
      reconstruction. The period of follow-up was an average of 25 (10-40) months.
      Twenty-six patients were clinically stable and asymptomatic at follow-up. Six
      patients were considered clinically unstable and all had associated ACL
      reconstruction and required a repeat arthroscopy. Two meniscal repairs failed to
      heal, and the broken meniscus arrow was retrieved arthroscopically 6 months after
      the primary operation. In four cases the meniscal tear healed completely (two
      cases) or partially. Otherwise, there were no objective signs of complications.
      The use of meniscus arrows is a simple, safe, and reliable method for repair of
      properly selected meniscal tears.

PMID- 12185530
TI  - Arthroscopic treatment of patellar symptoms in posterior stabilized total knee
      replacement.
AB  - Twenty-one patients with patellar symptoms had arthroscopic treatment. Symptoms
      included frank patellar clunk and painful patellofemoral crepitus. All patients
      had posterior stabilized total knee replacement (TKR). The average onset of
      symptoms following TKR was 17 (range 3-75) months. All patients were referred to
      physiotherapy treatment before arthroscopic treatment. The average duration of
      symptoms prior to arthroscopic treatment was 23 (range 4-92) months. All patients
      were satisfied with resolution of symptoms at average follow-up of 32 (range 12
      52) months. No complications were encountered; however, one patient had
      recurrence of a painful patellar crepitus 8 months after arthroscopy.

PMID- 12185531
TI  - Tarsal tunnel syndrome - the effect of the associated features on outcome of
      surgery.
AB  - Between 1989 and 2000, 16 patients underwent surgery for tarsal tunnel syndrome;
      12 patients (13 feet) were available for follow-up at a mean of 83 (12-143)
      months. The symptoms had resolved in six feet, were improved in four, were
      unchanged in two and recurred after five years in one. Better results are
      obtained in patients who have space occupying lesions than in those in whom the
      aetiology is idiopathic or post-traumatic or those with foot deformities.

PMID- 12185532
TI  - Three new human members of the lipid transfer/lipopolysaccharide binding protein
      family (LT/LBP).
AB  - We have identified three novel, rarely expressed human genes that encode new
      members of the lipid transfer/lipopolysaccharide binding protein (LT/LBP) gene
      family based on sequence homology. BPI and other members of the LT/LBP family are
      structurally related proteins capable of binding phospholipids and
      lipopolysaccharides. Real-time PCR studies indicate that BPIL1 and BPIL3 are
      highly expressed in hypertrophic tonsils. In situ hybridization analysis of BPIL2
      shows prominent expression in skin specimens from psoriasis patients. BPIL1 and
      BPIL3 map to Chromosome 20q11; thus, these novel genes form a cluster with BPI
      and two other members of the LT/LBP gene family on the long arm of human Chr 20.
      BPIL2maps to Chr 22q13. The exon/intron organization of all three genes is highly
      conserved with that of BPI, suggesting evolution from a common ancestor.

PMID- 12185533
TI  - Identification of novel candidate genes in the diffuse panbronchiolitis critical
      region of the class I human MHC.
AB  - Diffuse panbronchiolitis (DPB) is an unusual form of bronchiolar disease
      affecting exclusively East Asians. Strong associations of DPB with the class I
      human leukocyte antigens HLA-B54 in Japan and China and HLA-A11 in Korea suggest
      that the susceptible locus for DPB is located between the HLA-B and HLA-A genes.
      We have previously reported that the susceptibility gene for DPB could be
      localized within a 200-kb segment between the S and TFIIH loci in the HLA class I
      region, using refined microsatellite-based association mapping. However, no genes
      have been recognized in this candidate region to date. In order to identify a
      novel candidate gene for DPB from this segment, the expressed sequence tag
      databases were searched using the genomic sequence. As a result, a cDNA clone was
      isolated from a human lung cDNA library. This gene, designated C6orf37
      (Chromosome 6 open reading frame 37), spans approximately 2.5 kb and consists of
      two exons encoding a 235-amino acid protein, sharing homology with the mucin-like
      domain of human zonadhesin, which is a sperm multiple-domain transmembrane
      protein with the sperm zona pellucida binding activity. Unexpectedly, RT-PCR
      analysis detected transcripts from the anti-sense DNA strand of this C6orf37
      locus. The gene designated as C6orf37OS (C6orf37 Opposite Strand) and represented
      by these anti-sense transcripts contained no open reading frame. The transcripts
      from C6orf37 and C6orf37OS were observed in numerous tissues, with most-abundant
      expression in lung, kidney, and testis. Taken together, these results, especially
      the abundant expression in lung, indicate that C6orf37 and C6orf37OS are
      excellent candidate genes for DPB.

PMID- 12185534
TI  - Association of CTLA-4 variation with type I diabetes in Filipinos.
AB  - The role of non-HLA single nucleotide polymorphisms from a panel of candidate
      genes in genetic susceptibility to type I diabetes (TID) among Filipinos was
      examined by PCR/SSOP typing of 90 patients and 94 controls, previously typed for
      the HLA class I and class II loci. We report the association of CTLA-4 A49G
      variation (cytotoxic T-lymphocyte associated-4) to TID among Filipinos,
      consistent with some but not all previous reports in other ethnic groups. The G
      allele frequency (0.61 versus 0.45, P=0.003) and GG genotype frequency (0.42
      versus 0.22, P=0.004) were each increased in patients compared to controls,
      respectively. Among Filipinos, the CTLA-4 genotypes are associated with disease
      only in the presence of the predisposing DR3, 4, and 9 haplotypes (P=0.012).
      Compared to the AA genotype, the increased risk of diabetes predisposition is
      greatest in genotype GG bearing the DR susceptible alleles (DR3, 4, and 9) (odds
      ratio=4.6, P=0.001), demonstrating that non- HLA loci, acting in concert with
      HLA, can play potent roles in modifying susceptibility to TID.

PMID- 12185535
TI  - Some human KIR haplotypes contain two KIR2DL5 genes: KIR2DL5A and KIR2DL5B.
AB  - Killer-cell immunoglobulin-like receptors (KIR) comprise a family of structurally
      diverse proteins encoded by a compact cluster of genes located in human
      Chromosome 19q13.4. The most recently described member of the KIR family,
      KIR2DL5, is represented in human populations by at least four gene variants,
      whose exons differ by two to eight nucleotides. We show here that these
      structurally similar variants are encoded by alleles of two different loci,
      KIR2DL5A and KIR2DL5B, which map to different regions of the KIR-gene cluster.
      Regarding KIR2DL5, four groups of KIR haplotypes can be distinguished: those
      having both KIR2DL5A and KIR2DL5B, those having either KIR2DL5A or KIR2DL5B, and
      those lacking KIR2DL5. Positive association between KIR2DL5A and KIR2DL5B was
      detected but did not reach statistical significance. These results are consistent
      with a model in which KIR2DL5A and KIR2DL5B are products of a gene duplication,
      which through the action of subsequent recombination have became separated on
      some haplotypes.

PMID- 12185536
TI  - Unique haplotypes of co-segregating major histocompatibility class II A and class
      II B alleles in Atlantic salmon (Salmo salar) give rise to diverse class II
      genotypes.
AB  - Sequence-based typing of a breeding population (G1) consisting of 84 Atlantic
      salmon individuals revealed the presence of 7 Sasa-DAA and 7 Sasa-DAB expressed
      alleles. Subsequent typing of 1,182 individuals belonging to 33 families showed
      that Sasa-DAA and Sasa-DAB segregate as haplotypes. In total seven unique
      haplotypes were established, with frequencies in the population studied ranging
      from 0.01 to 0.49. Each haplotype is characterized by a unique minisatellite
      marker size embedded in the 3' untranslated region of the Sasa-DAA gene. These
      data corroborate the fact that Atlantic salmon express a single class II locus,
      consisting of tightly linked class II A and class B genes. The seven haplotypes
      give rise to 15 genotypes with frequencies varying between 0.01 and 0.23; 21
      class II homozygous individuals were present in the G1 population. We also
      studied the frequency distribution in another breeding population (G4, n=374)
      using the minisatellite marker. Only one new marker size was present, suggesting
      the presence of one new class II haplotype. The marker frequency distribution in
      the G4 population differed markedly from the G1 population. The genomic
      organizations of two Sasa-DAA and Sasa-DAB alleles were determined, and supported
      the notion that these alleles belong to the same locus. In contrast to other
      studies of salmonid class II sequences, phylogenetic analyses of brown trout and
      Atlantic class II A and class II B sequences provided support for trans-species
      polymorphism.

PMID- 12185538
TI  - Sequence analysis of MHC DRB alleles in domestic cats from the United Kingdom.
AB  - The DRB gene of the domestic cat MHC appears to be highly polymorphic, with 71
      alleles provisionally reported, based on exon 2 sequence. However, these alleles
      were reported prior to the adoption of strict criteria for allele identification.
      In this study, we investigated FLA-DRB exon 2 polymorphisms in a cohort of 33
      British domestic cats by polymerase chain reaction (PCR) and clonal sequence
      analysis. Applying the strict criteria for assigning new alleles as used by the
      established mammalian MHC nomenclature committees, we defined 13 FLA-DRB alleles,
      including four previously unreported alleles. We identified many sequences that
      were one or two base pairs different from these 13 defined alleles, and have
      shown that these are most likely artefacts of PCR amplification. When the same
      criteria for allele acceptance were applied to the remaining previously reported
      sequences, 11 further alleles were confirmed. This suggests that to date there is
      good evidence for 24 FLA-DRB alleles fulfilling nomenclature criteria. Analysis
      of these 24 alleles reveals a similar pattern of MHC polymorphism to that seen in
      other mammals, with three regions of hypervariability.

PMID- 12185537
TI  - Molecular characterization of expressed DQA and DQB genes in the California sea
      lion ( Zalophus californianus).
AB  - To date, there are no published MHC sequences from the California sea lion
      (Zalophus californianus), a thriving species that, by feeding high on the marine
      food web, could be a sentinel for disturbances in marine and coastal ecosystems.
      In this study, degenerate primers and RACE technology were used to amplify near
      full-length (MhcZaca- DQB) and full-length (MhcZaca- DQA) expressed class II MHC
      gene products from the peripheral blood mononuclear cells of two California sea
      lions in rehabilitation. Five unique Zaca- DQA sequences and eight unique Zaca-
      DQB sequences, all encoding functional proteins, were identified in the two
      animals, indicating the presence of multiple DQ- loci in this species. An
      additional three Zaca- DQB sequences containing features compatible with
      pseudogenes or null alleles were also identified. Despite the identification of
      multiple DQA and DQB sequences, the degree of heterogeneity between them was
      extremely low. To confirm the limited degree of Zaca-DQ nucleotide variation
      between individuals, we used denaturing gradient gel electrophoresis to examine
      putative peptide binding region sequences from the peripheral blood leukocyte
      derived RNAs of 19 wild-caught California sea lions from physically distinct
      populations. The pattern of Zaca-DQ sequence migration was identical between
      individuals and independent of geographical region. This apparent Zaca-DQ
      sequence identity between sea lions was confirmed by direct sequencing of
      individual bands. In combination, these findings raise important questions
      regarding immunogenetic diversity within this thriving species, and should prompt
      further research into the existence of a highly polymorphic sea lion class II MHC
      molecule with sequence features that support traditional peptide binding
      functions.

PMID- 12185539
TI  - Evolution of the six horse IGHG genes and corresponding immunoglobulin gamma
      heavy chains.
AB  - It is generally assumed that the different mammalian IgG isotypes have developed
      during evolution by duplications of a common ancestor gamma heavy chain constant
      region gene (IGHG). In contrast to other species studied so far, which express
      between one and four IGHG genes, the horse (Equus caballus) genome contains six
      IGHG genes, and it has been postulated that they all can be expressed. For
      determination of the evolutionary history of the six horse IGHG genes, genomic
      DNA and cDNA of the IGHG genes were sequenced. The structure of these genes with
      reference to exons and introns was determined. Comparison of the deduced amino
      acid sequences of the horse IGHG genes revealed the greatest divergences in the
      hinge regions, and in the proximal CH2 domains. A phylogenetic comparison of the
      amino acid sequences of the six horse IGHG genes to those of other species shows
      that the horse IGHG genes form a distinct cluster. This indicates that the
      mammalian species included in this study probably share only one common ancestor
      IGHG gene with the horse. The six horse IGHG genes probably then evolved by gene
      duplication after species separation. In addition, various segmental exchanges
      were found between the horse IGHG genes, which might be the result of unequal
      crossing over and/or gene conversion events during the evolution of the six horse
      IGHG genes.

PMID- 12185541
TI  - Abnormalities of cerebellar foliation and fissuration: classification,
      neurogenetics and clinicoradiological correlations.
AB  - Several genes have been found to influence the different cells involved in the
      processes of foliation and fissuration in the mouse and rat cerebellum. In the
      light of these new concepts and on the basis of the imaging findings in 42
      patients, a classification is proposed for abnormalities of foliation and
      fissuration. On the basis of recent genetic and experimental evidence on
      mechanisms which control the origin of the cerebellum, it is suggested that
      abnormalities of foliation and fissuration form a single group, with a spectrum
      of severity. Some patients have only abnormal fissuration of the anterior lobe
      (type 1a) and others additional dysplasia of the anterior and part of the
      posterior lobe (type 1b). Extension of abnormalities into the hemispheres is
      often seen in the latter group. A second group has vermian and hemisphere
      abnormalities (type 2). In addition to the malformation of the anterior lobe of
      the vermis, three different hemispheric lesions can be seen in this group:
      cortical dysgenesis, hypertrophy of the cerebellar cortex, and malorientation of
      the folia. The mild abnormalities (type 1a) can be considered an incidental
      observation without clinical relevance. The moderate and severe cerebellar
      anomalies (type 1b and 2) are always associated with cerebellar symptoms and/or
      signs.

PMID- 12185542
TI  - Polymicrogyria without porencephaly/schizencephaly. MRI analysis of the spectrum
      and the prevalence of macroscopic findings in the clinical population.
AB  - Although the diagnosis of polymicrogyria currently depends largely on non
      invasive imaging, no large imaging-based studies of polymicrogyria have been
      reported. Previous anatomic studies of polymicrogyria have been based on autopsy
      studies and most of the cases in those series were associated with porencephaly
      or schizencephaly. This retrospective MRI analysis of a group of patients with
      polymicrogyria, without associated porencephaly or schizencephaly, was conducted
      to elucidate gross morphological findings of polymicrogyria in a clinical
      population. Seventy-one patients with polymicrogyria diagnosed by MRI were
      reviewed by two radiologists. The location of polymicrogyria, the associated
      white matter anomalies and other associated central nervous system anomalies were
      assessed. The polymicrogyria was unilateral in 30 (42%) patients, bilateral in 41
      (58%) patients. The lobes involved in polymicrogyria were frontal 69%, parietal
      63%, temporal 38%, and occipital 7%. The cortex in the Sylvian fissures was
      involved in 80%. The striate cortex, cingulate gyrus, hippocampus and the gyrus
      rectus were often spared. Diminished volume of white matter was noted in 48%,
      perivascular space dilatation in 27% and large cortical veins in 51%.
      Polymicrogyria develops in specific topological regions, the majority being
      centered around the Sylvian fissures, and a minority in the inferior and medial
      aspects of the cerebral hemispheres or the occipital lobes. Diminished volume of
      the white matter and dilated perivascular spaces deeply embedded close to the
      dysplastic cortex and abnormal cortical venous enlargement superficial to the
      dysplastic cortex may be useful adjuncts in making the diagnosis.

PMID- 12185543
TI  - Cerebral gliomas: prospective comparison of multivoxel 2D chemical-shift imaging
      proton MR spectroscopy, echoplanar perfusion and diffusion-weighted MRI.
AB  - Developments in MRI have made it possible to use diffusion-weighted MRI,
      perfusion MRI and proton MR spectroscopy (MRS) to study lesions in the brain. We
      evaluated whether these techniques provide useful, complementary information for
      grading gliomas, in comparison with conventional MRI. We studied 17 patients with
      histologically verified gliomas, adding multivoxel proton MRS, echoplanar
      diffusion and perfusion MRI the a routine MRI examination. The maximum relative
      cerebral blood volume (CBV), minimum apparent diffusion coefficient (ADC) and
      metabolic peak area ratios in proton MRS were calculated in solid parts of
      tumours on the same slice from each imaging data set. The mean minimum ADC of the
      13 high-grade gliomas (0.92+/-0.27 x 10(-3) mm(2)/s) was lower than that of the
      four low-grade gliomas (1.28+/-0.15 x 10(-3) mm(2)/s) ( P<0.05). Means of maximum
      choline (Cho)/N-acetylaspartate (NAA), Cho/creatine (Cr), Cho/Cr in normal brain
      (Cr-n) and minimum NAA/Cr ratios were 5.90+/-2.62, 4.73+/-2.22, 2.66+/-0.68 and
      0.40+/-0.06, respectively, in the high-grade gliomas, and 1.65+/-1.37, 1.84+/
      1.20, 1.61+/-1.29 and 1.65+/-1.61, respectively, in the low-grade gliomas.
      Significant differences were found on spectroscopy between the high- and low
      grade gliomas ( P<0.05). Mean maximum relative CBV in the high-grade gliomas
      (6.10+/-3.98) was higher than in the low-grade gliomas (1.74+/-0.57) ( P<0.05).
      Echoplanar diffusion, perfusion MRI and multivoxel proton MRS can offer
      diagnostic information, not available with conventional MRI, in the assessment of
      glioma grade.

PMID- 12185544
TI  - Developing a comprehensive presurgical functional MRI protocol for patients with
      intractable temporal lobe epilepsy: a pilot study.
AB  - Our aim was to put together and test a comprehensive functional MRI (fMRI)
      protocol which could compete with the intracarotid amytal (IAT) or Wada test for
      the localisation of language and memory function in patients with intractable
      temporal lobe epilepsy. The protocol was designed to be performed in under 1 h on
      a standard 1.5 tesla imager. We used five paradigms to test nine healthy right
      handed subjects: complex scene-encoding, picture-naming, reading, word-generation
      and semantic-decision tasks. The combination of these tasks generated two
      activation maps related to memory in the mesial temporal lobes, and three
      language-related maps of activation in a major part of the known language
      network. The functional maps from the encoding and naming tasks showed typical
      and symmetrical posterior mesial temporal lobe activation related to memory in
      all subjects. Only four of nine subjects also showed symmetrical anterior
      hippocampal activation. Language lateralisation was best with the word generation
      and reading paradigms and proved possible in all subjects. The reading paradigm
      enables localisation of language function in the left anterior temporal pole and
      middle temporal gyrus, areas typically resected during epilepsy surgery. The
      combined results of this comprehensive f MRI protocol are adequate for a
      comparative study with the IAT in patients with epilepsy being assessed for
      surgery.

PMID- 12185545
TI  - Value of conventional, and diffusion- and perfusion weighted MRI in the
      management of patients with unclear cerebral pathology, admitted to the intensive
      care unit.
AB  - The aim of our retrospective study was to determine the extent to which diffusion
      and perfusion- weighted MRI combined with conventional MRI could be helpful in
      the evaluation of intensive care unit (ICU) patients who have unknown or unclear
      cerebral pathology underlying a serious clinical condition. Twenty-one ICU
      patients with disparity between the findings on brain CT scan and their clinical
      status were studied. All patients underwent conventional MR and diffusion
      weighted imaging and 14 also had MR perfusion studies. Abnormalities were present
      on diffusion-weighted imaging of 17 of the 21 patients and on perfusion-weighted
      studies of 7 of 14 patients. The MRI results changed the preliminary/working
      diagnosis in six patients. In eight other patients, MRI revealed additional
      pathology that had not been suspected clinically, and/or characterized more
      closely findings that had already been detected by CT or suspected clinically.
      MRI showed abnormalities in four of the five patients who had normal CT. MRI
      findings suggested a negative clinical outcome in all nine patients who
      subsequently died. MRI findings also suggested positive long-term outcome in five
      of nine patients who improved significantly as based on Glasgow and extended
      Glasgow outcome scales. In the three unconscious patients who had normal
      diffusion- and perfusion-weighted imaging the clinical outcome was good. This
      study suggests that MRI in seriously ill ICU patients with unclear cerebral
      pathology can provide information that changes, characterizes, or supports
      diagnoses and/or prognoses and therefore facilitates further management.

PMID- 12185546
TI  - Fast contrast-enhanced MR whole-brain venography.
AB  - Our aim was to assess the value of a new fast contrast-enhanced MR venography (CE
      MRV) sequence in the investigation of normal and diseased cerebral veins.
      Conventional time-of-flight (TOF) MRV is time consuming, with imaging for a
      single sequence taking many minutes. MRI was performed with a clinical 1.5-T
      scanner; conventional TOF MRV followed by CE-MRV was performed using a modified
      3D first-pass MR angiography sequence. Ten control subjects without cerebral
      pathology were studied as well as ten patients with cerebral venous thrombosis
      for a total of 20 studies with both sequences. CE-MRV was able to provide a set
      of complete MRV images in a significantly shorter time than conventional MRV
      sequencing could. The field of view also provided greater coverage of the vessels
      of the head and neck. CE-MRV also provided more extensive small vein detail and
      provided a better demonstration of intraluminal defects, despite a slightly lower
      resolution. Both methods were equally suited for the demonstration of venous
      thrombosis and demonstrated all cases equally well; however, CE-MRV provided more
      detailed information by showing partially obstructed sinuses and by showing
      better the presence of cortical collateral venous drainage.

PMID- 12185547
TI  - Cerebral angiography in the rat with mammographic equipment: a simple, cost
      effective method for assessing vasospasm in experimental subarachnoid
      haemorrhage.
AB  - We report quantification of vasospasm following subarachnoid haemorrhage (SAH)
      and the effect of a new antivasospastic free radical scavenger (AVS) in rats,
      using an angiographic technique developed in our laboratory. We acquired single
      exposure angiograms with mammographic equipment, using a 0.1 mm diameter focal
      spot and single-emulsion mammographic films. Contrast medium was injected through
      a PE50 catheter in the common carotid artery, after the external carotid artery
      had been ligated to divert flow towards the internal carotid artery territory.
      Measurements of the M1 and A1 segments and of the middle third of the basilar
      artery were made by projecting the angiograms directly as slides and using the
      endovascular catheter as an internal reference. We tested the technique on 40
      male albino Sprague-Dawley rats divided into four groups: sham-operated+saline,
      SAH+saline, sham-operated+AVS and SAH+AVS. We were able to measure the diameter
      of the principal intracranial arteries in all the animals. With our technique,
      which is cost-effective when compared to many of those reported recently, we
      could detect intracranial vasospasm in all untreated rats with SAH, and confirm
      antivasospastic effects of AVS.

PMID- 12185549
TI  - Endovascular parent artery occlusion in large-giant or fusiform distal posterior
      cerebral artery aneurysms.
AB  - Posterior cerebral artery aneurysms are amenable to deconstructive surgical
      treatment because of the rich collateral supply of the distal posterior cerebral
      artery. This report retrospectively analyses the outcome of endovascular parent
      artery occlusion for large or fusiform distal posterior cerebral artery
      aneurysms. Medical records and cerebral angiograms from two endovascular centres
      were analysed retrospectively. Eight patients with large or fusiform distal
      posterior cerebral artery (PCA) aneurysms were treated by endovascular occlusion
      of the segment of the PCA at the site of the aneurysm. Three of those were
      treated urgently after acute subarachnoid haemorrhage, the remainder had elective
      treatment. The clinical and angiographic outcomes in seven patients were assessed
      at 6 to 12 months. A single case of occipital infarction resulting in permanent
      homonymous hemianopia was the only permanent complication. Of the remaining
      patients, six made excellent recoveries and one was lost to follow-up. No
      recurrence or re-bleeding was noted. Endovascular parent artery occlusion may be
      an alternative to surgical parent artery occlusion in distal PCA aneurysms which
      are not convenient for selective endovascular treatment or surgical clipping.

PMID- 12185550
TI  - Stent-assisted angioplasty for intracranial atherosclerosis.
AB  - We report on two patients with intracranial atherosclerosis of the carotid artery
      or vertebral artery treated with stent-assisted angioplasty. Both patients have
      severe intracranial atherosclerosis (>70%) with refractory symptoms despite
      optimal medical treatment. In both patients, a coronary balloon-expandable stent
      was successfully placed using a protective balloon technique without procedural
      complications. The patients were asymptomatic and neurologically intact at a mean
      clinical follow-up of 13 months. Follow-up angiograms did not show restenosis 3
      or 4 months after procedure, respectively. Stent-assisted angioplasty for
      intracranial atherosclerosis in the elective patient has proven effective, with
      an acceptable low rate of morbidity and mortality.

PMID- 12185548
TI  - Local intra-arterial thrombolysis in the carotid territory: does recanalization
      depend on the thromboembolus type?
AB  - Little is known about whether recanalization of carotid territory occlusions by
      local intra-arterial thrombolysis (LIT) depends on the type of the occluding
      thromboembolus. We retrospectively analysed the records of 62 patients with
      thromboembolic occlusions of the intracranial internal carotid artery (ICA)
      bifurcation or the middle cerebral artery who were undergoing LIT with urokinase
      within 6 h of symptom onset. We determined the influence of thromboembolus type
      (according to the TOAST criteria), thromboembolus location, leptomeningeal
      collaterals, time interval from onset of symptoms to onset of thrombolysis, and
      patient's age on recanalization. The thromboembolus type was atherosclerotic in
      six patients, cardioembolic in 29, of other determined etiology in four, and of
      undetermined etiology in 23 patients. Thirty-three (53%) thromboembolic
      occlusions were recanalized. The thromboembolus location but not the TOAST stroke
      type nor other parameters affected recanalization. In the TOAST group of patients
      with cardioembolic occlusions recanalization occurred significantly less
      frequently when transoesophageal echocardiography showed cardiac thrombus. The
      present study underlines the thromboembolus location as being the most important
      parameter affecting recanalization. The fact that thromboembolic occlusions
      originating from cardiac thrombi had a lower likelihood of being resolved by
      thrombolysis indicates the thromboembolus type as another parameter affecting
      recanalization.

PMID- 12185552
TI  - Non-invasive assessment of selective 5-HT(1B/1D)-receptor agonist-induced
      peripheral vascular effects in humans: comparison of different techniques.
AB  - OBJECTIVE: To compare the sensitivity of three non-invasive techniques for
      detecting serotonin (5-HT)(1B/1D)-receptor agonist-induced peripheral vascular
      effects in humans: the measurement of (1) systolic (SBP) and diastolic (DBP)
      blood pressures, (2) dorsal hand vein (DHV) diameter and (3) toe-arm systolic
      blood pressure gradient (DeltaSBP(toe-arm)). METHODS: A double-blind, placebo
      controlled, three-way, cross-over study was performed in 12 healthy male
      volunteers. According to a randomly assigned allocation schedule, subjects were
      administered sumatriptan 3 mg, sumatriptan 6 mg or placebo subcutaneously.
      Measurements were performed at baseline, every 5 min for 30 min and at 40 min and
      60 min after drug administration. SBP and DBP were recorded using a semi
      automated oscillometric device. DHV diameter was measured using a linear variable
      differential transformer. DeltaSBP(toe-arm) was calculated after measuring toe
      and arm SBP with a strain-gauge technique. Sensitivity was evaluated with
      responsiveness statistics. RESULTS: Based on weighted mean and compared with
      placebo, sumatriptan 3 mg and 6 mg increased SBP by 3.3 mmHg ( P=0.023) and 6.4
      mmHg ( P<0.001) and DBP by 5.0 mmHg ( P=0.006) and 7.5 mmHg ( P<0.001),
      respectively. Sumatriptan 3 mg and 6 mg decreased DHV diameter by 36% ( P=0.015)
      and 40% ( P=0.005), respectively. DeltaSBP(toe-arm) did not change. Peak changes
      were observed within 10-15 min after drug administration. The rank order of
      responsiveness was: BP > DHV diameter > DeltaSBP(toe-arm.) CONCLUSIONS:
      Clinically relevant doses of subcutaneous sumatriptan increased blood pressure
      and decreased DHV diameter without affecting DeltaSBP(toe-arm). The increase in
      blood pressure appeared to be dose dependent. Compared with DHV diameter and
      DeltaSBP(toe-arm), blood pressure measurement appeared to be the most sensitive
      technique for detecting selective 5-HT(1B/1D)-receptor agonist-induced peripheral
      vascular effects in humans.

PMID- 12185553
TI  - Comparative effects of tobacco smoking and nasal nicotine.
AB  - OBJECTIVE: Compare the electroencephalographic (EEG) and cardiovascular effects
      of tobacco smoking and nasal nicotine in the same subjects. METHODS: Eleven
      volunteer smokers were studied after >10 h of overnight tobacco deprivation.
      Quantitative EEG was used to measure brain electrical changes produced by four
      different treatments. Each subject smoked a low (0.08 mg) and average nicotine (1
      mg) yield cigarette on one test day and received placebo and nicotine nasal spray
      (0.5 mg/spray) on a second day in a counterbalanced design. EEG activity was
      measured from 16 scalp electrodes and analyzed as delta, theta, alpha (1), alpha
      (2), beta (1), and beta (2) frequency bands. Heart rate (HR), blood pressure
      (BP), and plasma venous nicotine concentrations (VNC) were monitored during both
      sessions. EEG data from all 16 channels at each of six frequencies were compared
      over 10 min using repeated measures ANOVA analysis. Changes in HR, BP, and VNC
      from baseline were compared using ANOVA followed by post hoc Scheffe's test.
      RESULTS: Smoking an average nicotine delivery cigarette resulted in highly
      significant decreases in alpha (1) activity, significant increases in alpha (2)
      activity, and significant increases in both HR and VNC compared to all other
      conditions. CONCLUSION: When smokers are allowed to pace themselves, cigarette
      smoking is far more effective than nasal nicotine in activating the EEG and
      increasing HR and VNC. This lack of equivalent physiological effects may explain
      the low success rate when nicotine nasal spray is used by those trying to quit
      smoking.

PMID- 12185554
TI  - Effects of cigarette smoking on quinine pharmacokinetics in malaria.
AB  - OBJECTIVE: Quinine is an important antimalarial drug that is metabolised mainly
      by the hepatic mixed-function microsomal enzyme cytochrome P(450). Cigarette
      smoking in healthy volunteers has been reported to enhance quinine clearance. The
      present study evaluated the effects of smoking on quinine pharmacokinetics in
      patients with uncomplicated falciparum malaria treated with a 7-day course of
      oral quinine. Of 22 studied male patients, 10 were regular smokers and 12 were
      non-smokers. METHODS: All patients were treated with a 7-day oral regimen of
      quinine sulfate (10 mg salt/kg three times a day). Serial venous blood samples
      were taken for quinine levels before and during treatment at 12 h and 24 h and
      then daily until day 7. Plasma quinine and 3-hydroxyquinine concentrations were
      assayed using high-performance liquid chromatography. Quinine pharmacokinetics
      were evaluated using non-compartmental modelling. RESULTS: All patients
      recovered, and there were no significant differences in clinical responses or
      cure rates between the two studied groups ( P> or =0.32). The median (range)
      fever clearance time was 51 h (4-152 h) and mean (SD) parasite clearance time was
      74+/-28 h. The overall median times to maximum concentrations of quinine and its
      main metabolite 3-hydroxyquinine were 1.5 days and 4.0 days, respectively. The
      maximum concentrations of quinine were approximately tenfold higher than 3
      hydroxyquinine. There were no significant differences in any pharmacokinetic
      variables for the parent compound or metabolite between the two groups. The
      median area under the plasma drug concentration-time curve to day 7 (AUC(0-7)) of
      quinine in non-smokers was 67.0 micro g/ml/day and in smokers was 51.3 micro
      g/ml/day, and AUC(0-7) values of 3-hydroxyquinine were 6.2 micro g/ml/day and 4.8
      micro g/ml/day, respectively. CONCLUSION: These results indicated that cigarette
      smoking has no significant effects on quinine pharmacokinetics or the therapeutic
      response in patients with falciparum malaria.

PMID- 12185555
TI  - Bacterial pneumonia can increase serum concentration of clozapine.
AB  - Concentrations of serum clozapine, C-reactive protein (CRP) and alpha1 acid
      glycoprotein were greatly increased during a bacterial pneumonia in a 53-year-old
      woman. As the pneumonia subsided, and CRP and alpha1 acid glycoprotein
      normalised, serum clozapine concentration also decreased to the previous level.
      An increased serum clozapine and a lowered N-desmethylclozapine to clozapine
      ratio during the infection suggest a decreased cytochrome P(450) (CYP)1A2
      activity. Cytokine-mediated CYP1A2 suppression is discussed.

PMID- 12185556
TI  - Steady-state concentration of venlafaxine enantiomers: model-based analysis of
      between-patient variability.
AB  - OBJECTIVE: To investigate patients treated for depression with respect to steady
      state concentration of venlafaxine enantiomers, to quantify within- and between
      subject variability and to study the possible influence of individual
      characteristics such as gender and age. METHODS: Thirty-five inpatients received
      venlafaxine orally at a fixed 300-mg daily dose. Blood samples were taken on day
      14 and day 28 for therapeutic drug monitoring purposes. All measurements
      reflected steady-state trough values. In a first stage, plasma concentrations of
      racemic venlafaxine (V) and O-desmethylvenlafaxine (ODV) were measured using a
      gas chromatography method. In a second stage, (+)/(-) enantiomeric ratios for V
      and ODV were determined using a stereoselective capillary electrophoresis method.
      RESULTS: Interindividual variability was 77% and 33% for concentrations of
      racemic V and ODV, respectively. Intraindividual variability was below 20% for
      both compounds. Enantiomeric ratios did not statistically differ from unity, with
      median (+)/(-) ratios of 1.14 for V and 0.97 for ODV. ODV/V metabolite formation
      ratios for the (+) and (-) enantiomers did not significantly differ from each
      other (median values 2.85 and 2.37, respectively). However, reduced ODV/V ratio
      for the (-) enantiomer was strongly associated with decreased (+)/(-) ratio for V
      (r(S)=0.71, P<0.001) and increased (+)/(-) ratio for ODV (r(S)=-0.79, P<0.001).
      In contrast, ODV/V ratio for the (+) enantiomer did not significantly correlate
      with parent compound (+)/(-) ratio and correlated only weakly with metabolite
      (+)/(-) ratio (r(S)=-0.38, P<0.05). When compared with males, females displayed a
      significantly lower ODV/V ratio for the (-) enantiomer (median values 1.42 vs
      5.08 on day 14, P<0.05) but not for the (+) enantiomer (median values 2.36 vs
      3.27, n.s.). Analysis did not reveal any significant association between ODV/V
      ratios and age, weight, height, creatinine clearance, smoking or co-medication. A
      pharmacokinetic model at steady state was developed that postulated two different
      enzyme systems to contribute to O-desmethylation. ODV(-) formation was supposed
      to largely depend on a single pathway, possibly impaired in a patient
      subpopulation. ODV(+) formation was postulated to rely on both pathways to a
      similar extent. Model predictions were in close agreement with observations in
      patients. CONCLUSION: Observations, together with model-based simulations,
      suggested that marked stereoselectivity in a patient subgroup may be related with
      impairment of O-desmethylation greater for (-) than (+) venlafaxine. This
      hypothesis requires testing against phenotypic and genotypic characteristics of
      patients.

PMID- 12185557
TI  - Phenotypic polymorphism of CYP2A6 activity in a Chinese population.
AB  - AIMS: To investigate the distribution characteristics of CYP2A6 activity in a
      Chinese population and to examine the sex-related differences in CYP2A6
      activities. METHODS: One hundred and twenty healthy volunteers, 63 men and 57
      women, were included in the study. Cytochrome P450 (CYP) 2A6 activity was
      measured using the ratio of urinary 7-hydroxycoumarin (7-OHC) excreted in 8 h
      after a coumarin dose. The concentrations of 7-OHC in urine were determined using
      high performance liquid chromatography. RESULTS: A 300-fold interindividual
      variation of CYP2A6 activity was shown in the studied Chinese population. The
      coefficient of variation of CYP2A6 activity was 27.2%. A Kolmogorov-Smirnov test
      indicated a non-normal distribution of CYP2A6 activity ( P<0.001). Probit plots
      of CYP2A6 activity revealed a bimodal distribution with breakpoint of activity
      index near 0.47. The percentage of poor metabolizers (PMs) was 13.3% (95%
      confidence interval 7.3%-19.4%) in this population. Residual analysis also
      supported bimodality ( P<0.01). The CYP2A6 activities of females were obviously
      higher than those of males when the activity index was less than 0.74, although
      no statistically significant difference in the activity index of CYP2A6 between
      males and females was found. However, there was no sex-related difference in the
      incidence of PMs ( P>0.5). CONCLUSIONS: There are pronounced interindividual
      variations and phenotypic polymorphism of CYP2A6 activities in the Chinese
      population.

PMID- 12185558
TI  - Population pharmacokinetic and pharmacodynamic modelling of artemisinin and
      mefloquine enantiomers in patients with falciparum malaria.
AB  - OBJECTIVES: The aims of this study were to investigate whether artemisinin
      influences the pharmacokinetics of mefloquine enantiomers or vice versa and to
      model the antiparasitic effect of these drugs alone and in combination in
      Plasmodium falciparum malaria patients. METHODS: Forty-two male and female
      patients were randomised to treatment with either oral artemisinin 500 mg daily
      for 3 days followed by oral mefloquine 750 mg on day 4, oral artemisinin 500 mg
      daily for 3 days plus oral mefloquine 750 mg on day 1 or a single 750-mg oral
      dose of mefloquine. The data was modelled using NONMEM. RESULTS: All patients
      were successfully treated regardless of treatment. The fastest parasite clearance
      rates were observed in patients receiving artemisinin together with mefloquine on
      the first day of treatment. A pharmacodynamic model based on the life cycle of P.
      falciparum successfully described the efficacy of artemisinin, mefloquine and the
      combination. The time artemisinin concentration stays above a minimum inhibitory
      concentration was estimated to 2.97 h (relative standard error 4.7 h). The two
      mefloquine enantiomers exhibited different pharmacokinetics, with an oral
      clearance of 3.51 (7.9) l/h and 0.602 (6.9) l/h for RS-mefloquine and SR
      mefloquine, respectively. In patients receiving only artemisinin the first 3
      days, artemisinin oral clearance was 6.9-fold higher the last day of treatment
      compared with the first day. There was no difference in the pharmacokinetics of
      mefloquine enantiomers when mefloquine was given alone, in combination with
      artemisinin or after a 3-day regimen of artemisinin. There was a tendency
      towards, although non-significant, higher artemisinin concentrations when
      artemisinin was given together with mefloquine compared with when given alone.
      CONCLUSIONS: No significant pharmacokinetic interactions were observed after co
      administration of artemisinin and mefloquine. The P. falciparum malaria
      pharmacodynamic model successfully described the antimalarial effect of
      artemisinin, mefloquine and a combination of the two drugs.

PMID- 12185559
TI  - Morphine glucuronide-to-morphine plasma ratios are unaffected by the UGT2B7 H268Y
      and UGT1A1*28 polymorphisms in cancer patients on chronic morphine therapy.
AB  - OBJECTIVE: UDP-glucuronosyltransferase (UGT) 2B7 is the major UGT isoform
      responsible for the 3- and 6-glucuronidation of morphine in humans. Studies in
      rats have indicated that UGT1A1 may also contribute to the formation of morphine
      3-glucuronide (M3G). Our objective was to investigate whether the UGT2B7 H268Y
      and UGT1A1*28 polymorphisms contribute to the variability in morphine glucuronide
      to-morphine plasma ratios among cancer patients undergoing analgesic therapy with
      morphine. METHODS: Seventy patients with normal hepatic and renal function using
      slow-release morphine to relieve cancer pain were included. UGT2B7 genotyping was
      performed using restriction enzyme analysis of polymerase chain reaction (PCR)
      amplified DNA fragments. Wild-type and variant alleles of the UGT1A1 gene were
      identified using sizing of PCR-amplified fragments. Morphine 6-glucuronide
      (M6G)/morphine, M3G/morphine, and M3G/M6G plasma ratios were compared between
      genotypes. RESULTS: The M3G/morphine, M6G/morphine, and M3G/M6G plasma ratios
      varied 16-, 42-, and sevenfold, respectively, among individuals. No statistically
      significant differences in plasma ratios were found between individuals
      possessing UGT2B7 H/H ( n=20), H/Y ( n=30), or Y/Y ( n=20) genotypes. Five
      patients were homozygous for the UGT1A1 TA(7) allele, which is associated with
      reduced UGT1A1 gene expression. However, the mean M3G/M6G and M3G/morphine plasma
      ratios in TA(7) homozygous subjects did not differ significantly from those of
      heterozygous or homozygous wild-type (TA(6)) individuals. CONCLUSION: The UGT2B7
      H268Y polymorphism cannot account for the considerable variation in glucuronide
      to-morphine ratios in cancer patients. Moreover, the contribution of UGT1A1 to
      the formation of M3G appears to be of minor biological significance, at least in
      a UGT2B7 background.

PMID- 12185560
TI  - Modeling of human hepatic CYP3A4 enzyme kinetics, protein, and mRNA indicates
      deviation from log-normal distribution in CYP3A4 gene expression.
AB  - AIMS: To determine whether the variability in cytochrome P(450) (CYP)3A4
      metabolic function is exhibited at both transcription and translation levels and
      to examine the population distribution of CYP3A4 enzyme kinetics, protein, and
      mRNA. METHODS: Enzyme kinetics of testosterone 6beta-hydroxylation, immunoblot
      CYP3A4 protein, and CYP3A4 mRNA were determined in a microsomal bank of human
      livers. The distribution of these determinations was analyzed using cumulative
      distribution (probit) plots and normality test variable (NTV) to detect deviation
      from normality. RESULTS: Mean hepatic CYP3A4 protein and relative CYP3A4 mRNA
      were 35+/-23 pmol/mg and 79+/-59 (CYP3A4/beta-actin), respectively. Kinetic
      parameter estimates of testosterone 6beta-hydroxylation were 611+/-684
      pmol/mg/min for maximum rate of the reaction (V(max)) and 206+/-48 micro M for
      the Michaelis constant (K(m)). The CYP3A4 gene expression and its activity
      exhibited a relatively high degree of interindividual variability. Furthermore,
      significant correlation between CYP3A4 protein and V(max) of testosterone 6beta
      hydroxylation (r=0.82, P<0.001) as well as CYP3A4 protein and its mRNA (r=0.52,
      P<0.01) was observed. Cumulative distribution plots and histograms for the CYP3A4
      protein, its mRNA, and maximum testosterone 6beta-hydroxylation exhibited
      evidences of deviation from log-normal distribution. The minimum NTV value for
      the distribution of CYP3A4 protein corresponding to the inflection point in the
      probit occurred at approximately 10% cumulative frequency. The percentage of low
      CYP3A4 protein phenotype was consistent for CYP3A4 activity and its mRNA. In
      contrast, the distribution of K(m) of testosterone 6beta-hydroxylation does not
      show evidence of bimodality. CONCLUSIONS: The distribution of CYP3A4 metabolic
      function, protein, and mRNA is non-normal and may represent a regulatory
      polymorphism in hepatic CYP3A4 gene expression. In contrast, assessment of the
      possibility of a structural variant of CYP3A4 through evaluation of the standard
      deviation relative to the mean kinetic constant value suggests that structural
      mutation of CYP3A4 may not be a major factor affecting interindividual variation
      in CYP3A4 metabolic function.

PMID- 12185561
TI  - Adverse drug reactions and cognitive function among hospitalized older adults.
AB  - OBJECTIVE: To explore the relationship between cognitive function and the
      detection of adverse drug reactions (ADRs) and to evaluate whether cognitive
      function could influence the association between age and ADRs. METHODS: A total
      of 16,926 patients admitted to 81 hospitals throughout Italy between 1991 and
      1997 were included in the study. ADRs detected the during hospital stay were
      recorded by a study physician. Patients with a Hodkinson Abbreviated Mental Test
      (AMT) score <7 at hospital admission were considered cognitively impaired.
      RESULTS: A total of 1,444 ADRs were diagnosed in 976 patients (5.8% of the total
      sample). Overall, gastrointestinal complications (18.0% of all ADRs) were the
      most frequent ADRs, followed by cardiovascular (12.3%) and
      dermatological/allergic complications (12.3%). An ADR was recorded in 232/4,883
      (4.8%) patients with cognitive impairment and in 744/12,043 (6.2%) patients
      cognitively intact. After adjusting for potential confounders, cognitive
      impairment was associated with a reduced risk of ADRs (OR 0.70; 95% CI: 0.60
      0.83). This result was not consistent for all types of ADRs, since the risk of
      neuropsychiatric complications was significantly increased among patients with
      cognitive impairment (OR 2.23; 95% CI 1.40-3.54). The overall rate of ADRs was
      5.2% in patients younger than 65, 6.1% in patients between 65 and 79, and 5.8% in
      those 80 or older. When adjusting for potential confounders, not including the
      AMT score, age was not found to be significantly associated with ADRs. However,
      when the variable for the AMT score was introduced into the model, the risk for
      ADRs significantly increased with increasing age. CONCLUSION: Cognitive
      impairment is associated with a lower detection rate of ADRs, and it represents a
      confounder of the association between age and ADRs.

PMID- 12185562
TI  - Advances in optical spectroscopy and mass spectrometry. A tribute to David M.
      Hercules.

PMID- 12185563
TI  - On-chip absorption measurements using an integrated waveguide.
AB  - Square hollow waveguides are used to integrate measurement of absorption with
      chip-based electrophoresis. The 50x50 microm liquid channel and 50x50 microm
      waveguide are etched as a negative pattern into a silicon master and replicated
      as a positive in poly-dimethylsiloxane (PDMS). The uniform refractive index of
      the chip prevents guiding by total internal reflection. Instead, light at 488 nm
      is guided by reflection at the air-PDMS interface. The waveguide has a 60%
      efficiency over a distance of 3.2 cm. Separation of fluorescein and the dye
      BODIPY is demonstrated. A detection limit (S/N=3) of 200 microM fluorescein is
      obtained using a 50 microm pathlength and a simple photocell detector.

PMID- 12185564
TI  - Surface perspectives in the biomedical applications of poly(alpha-hydroxy acid)s
      and their associated copolymers.
AB  - Impressive advances in biotechnology, bioengineering, and biomaterials with
      unique properties have led to increased interest in polymers and other novel
      materials in biological and biomedical research and development over the past two
      decades. Although biomaterials have already made an enormous impact in biomedical
      research and clinical practice, there is a need for better understanding of the
      surface and interfacial chemistry between tissue (or cells) and biomedical
      materials. This is because the detailed physicochemical events related to the
      biological response to the surface of materials still often remain obscure, even
      though surface properties are important determinants of biomedical material
      function. In this regard, data available in the literature show the complexity of
      the interactions (surface reorganization, non-specific/specific protein
      adsorption, and chemical reactions such as acid-base, ion pairing, ion exchange,
      hydrogen bonding, divalent-ion bridging) and the interrelationship between
      biological environments, interfacial properties, and surface functional groups
      responsible for the biological responses. Because of the multidisciplinary nature
      of surface and interfacial phenomena at the surface of biomedical polymers, this
      review focuses on several aspects of current work published on poly(alpha-hydroxy
      acid)s and their associated copolymers:surface structure-biomedical function
      relationships;physicochemical strategies for surface modification; and,
      finally,synthetic strategies to increase biocompatibility for specific in-vivo
      and/or in-vitro biomedical applications.

PMID- 12185566
TI  - Surface characterization of WO(3)/ZrO(2) catalysts.
AB  - A series of WO(3)/ZrO(2) catalysts with tungsten (W) loadings ranging from 0.5 to
      11.4 wt% was prepared by incipient wetness impregnation on a preformed ZrO(2)
      support. The oxidic catalysts were characterized using XRD, Raman spectroscopy,
      XPS, ISS, and IR spectroscopy. XRD and Raman results showed that the ZrO(2)
      support was predominantly present in the monoclinic form. XPS and Raman
      measurements indicated the formation of increasing amounts of W interaction
      species for catalysts with W loadings up to 8.8 wt% WO(3). In addition to the W
      interaction species, bulk WO(3) was also observed for catalysts with W loadings >
      or = 3.0 wt% WO(3). Comparison of the XPS results with coverage measurements by
      ISS and CO adsorption suggests that the W surface phase is in the form of two
      dimensional polymeric patches for catalysts with W loadings 3.0 < or = wt% WO(3)
      < or = 4.5. For catalysts with W loadings >4.5 wt% WO(3), the results indicated
      an additional build-up of a bilayer (or multilayer) polymeric W species. Analysis
      of the hydroxyl region of ZrO(2) by IR spectroscopy showed that initial additions
      of W occur on the high frequency hydroxyl group. A schematic for the structure of
      the catalysts has been proposed based on the above observations.

PMID- 12185565
TI  - Dual-micro-ESI source for precise mass determination on a quadrupole time-of
      flight mass spectrometer for genomic and proteomic applications.
AB  - A universal dual-electrospray (ESI) source is demonstrated on a quadrupole
      orthogonal-accelerated time-of-flight mass spectrometer (Q-ToF-MS) for both
      genomic and proteomic applications. This facile source modification enables
      internal calibration for consistent mass measurements by a mainstream MS platform
      and requires no mixing of analyte and calibrant prior to ion formation. In this
      report, the dual-sprayer is demonstrated in the negative-ion mode for internal
      calibration of polymerase chain reaction (PCR) amplicons generated from synthetic
      and genomic templates as well as a proteolytic digest of a naturally
      phosphorylated protein. For all PCR amplicons, experimentally determined average
      mass measurements are well within the instrument specifications of better than
      0.01%. For the proteolytic fragments of the phosphoprotein, average mass errors
      of the isotopically resolved peptides are better than 10 ppm.

PMID- 12185567
TI  - A pH sensor based on force generated by pH-dependent polymer swelling.
AB  - We have demonstrated the feasibility of a new type of pH sensor by combining a
      bead of porous lightly crosslinked diethanolamine derivatized poly(vinylbenzyl
      chloride) with a strain gauge, i.e. a pressure sensitive resistor. The polymer
      bead is toughened with Kraton G1652, a styrene-ethylene,butylene-styrene triblock
      copolymer. The sensor is constructed so that the shrunken form of the bead is
      held in contact with the strain gauge with a small force. Increases in the
      hydrogen ion concentration protonate the diethanolamine introducing a positive
      charge onto the polymer backbone. This results in an electrostatic swelling force
      that causes the polymer to swell. This is detected as a change in strain gauge
      resistance that is readout via a Wheatstone bridge. When the pH of 0.10 M buffers
      is changed from 10 to 4, the response time is 390 s for a bead that is 0.25 mm in
      diameter in the shrunken state. The response varies with the square of the bead
      radius. The magnitude of the response is highly correlated with the penetration
      modulus, a measure of the extent to which the bead resists deformation when
      subjected to an external force. The response to pH appears to be shifted by the
      application of pressure in the sensor. This instrumentally simple approach to
      sensing has the potential to be stable and long-lived if the polymer bead can
      undergo a large number of swelling/shrinking cycles without changing mechanical
      properties.

PMID- 12185568
TI  - Applications of surface analytical techniques for study of the interactions
      between mercury and fluorescent lamp materials.
AB  - Several surface analytical techniques, including electron spectroscopy for
      chemical analysis (ESCA)(X-ray photoelectron spectroscopy) and sputtered neutral
      mass spectrometry (SNMS), were used to study the interaction between Hg and other
      components of fluorescent lamps, a very critical issue in lighting industries.
      Active sites, responsible for Hg interaction/deposition, can be successfully
      identified by comparing the x- y distribution (obtained by ESCA mapping) and
      depth distribution (available through SNMS) of respective lamp components with
      that of Hg. A correlation in both depth and x- y distribution is strong evidence
      of site preference for Hg interaction/deposition. A burial mechanism is, however,
      proposed when only depth distribution, not x- y, is correlated. Other modes of
      ESCA (high resolution, angle-resolved, etc.) were also helpful. Information about
      the valence states of the interacted Hg species would help to define the nature
      of the interaction.

PMID- 12185569
TI  - Use of DRYLAB to compare octadecylsilane and carbon supports for reversed-phase
      chromatography of triazine herbicide test solutes.
AB  - One of the most important aspects of method development in reversed-phase high
      performance liquid chromatography (RPLC) is the accurate prediction of the
      resolution as one or more experimental variables (usually the mobile-phase
      composition) are changed. By use of commercially available computer simulation
      programs, e.g. Drylab 2000, data from a few initial experimental runs are used to
      predict how the separation will vary with composition so that a computer program
      can then rapidly locate the optimum conditions. Assumption of a linear
      relationship between log k' (retention factor) and phi (volume fraction of
      organic modifier in the element) minimizes the number of initial runs required
      for a separation and is usually adequate when the range of phi is not large. In
      this work the linearity of plots of log k' against phi for octadecylsilane-coated
      silica (ODS) and carbon-coated zirconia (C-ZrO(2)) columns were compared and the
      plots were used to determine whether prediction of the separation of triazine
      herbicides was adequate. Analysis of the slopes and intercepts of such plots are
      presented for both types of columns.

PMID- 12185570
TI  - Surface analysis of polymers electrically improved by plasma-source ion
      implantation.
AB  - Inert-gas (Ar, Xe) and reactive-gas (O(2), N(2)) plasma-source ion-implantation
      (PSII) treatment of PI, PET, PS-BD, and MPPO surfaces was performed at an ion
      energy of 30 keV to improve the electrical properties of the polymers. The effect
      of ion energy, treatment time, rf frequency, and power on the surface resistivity
      of polymer was investigated. Depending on ion energy, dose, and ion species, the
      surface resistivity of the film was reduced by several orders of magnitude. XPS,
      TOF-SIMS, and SEM were used to characterize MPPO surfaces treated by Ar-PSII and
      Xe-PSII. From these measurements it was found that the improvement in surface
      resistivity after PSII treatment was related to graphite carbon or cross-linked
      carbon-double-bond species formed on the surface.

PMID- 12185571
TI  - Analytical utility of valence band X-ray photoelectron spectroscopy of iron and
      its oxides, with spectral interpretation by cluster and band structure
      calculations.
AB  - The valence band and core-level X-ray photoelectron spectroscopy (XPS) of iron
      and its oxides are reported, and the valence band spectra interpreted by various
      calculation models. The paper focuses upon the valence band region, which shows
      significant differences between the metal and the following oxidized iron
      species: FeO, Fe(3)O(4), alpha-Fe(2)O(3), gamma-Fe(2)O(3), alpha-FeOOH and gamma
      FeOOH. The core region is of little analytical value as a means of distinguishing
      between these species, but the valence band region shows significant differences.
      These differences are consistent with spectra predicted by cluster and band
      structure calculations. Cluster calculations are valuable as a means for
      interpreting the spectra of iron oxides with multiple iron sites and defect
      characteristics.

PMID- 12185572
TI  - A novel approach for coincidence ion mass spectrometry.
AB  - A novel approach is proposed for extracting a maximum of information from
      secondary ions ejected when surfaces are bombarded with keV mono or polyatomic
      ions. It is known that the event-by-event bombardment-detection mode allows
      identification of spatiotemporal relationships among individual secondary ions
      which in turn reveal surface composition within nanometric dimensions. We have
      devised a procedure for identifying spatiotemporal relationships among individual
      secondary ions without the requirement of pulsed sample interrogation (one single
      projectile at a time). The consequence of "mass separated time-of-flight mass
      spectrometry" is a much improved measurement duty cycle.

PMID- 12185573
TI  - Oligonucleotide analysis with MALDI-ion-mobility-TOFMS.
AB  - Matrix-assisted laser-desorption ionization followed by ion-mobility separation
      and time-of-flight mass analysis (MALDI-IM-TOFMS) has been used to characterize
      native and chemically modified DNA oligonucleotides up to eight bases in length.
      Mobility resolution between 20 and 30 can be used to separate oligonucleotides of
      different length, but not to differentiate between isomers or even different
      compositions of the same length. MALDI-IM-TOFMS does, however, have additional
      utility in the analysis of mixtures of DNA oligonucleotides and peptides, because
      these classes of molecules can be distinguished on the basis of differences in
      their mobility. Oligonucleotide sequencing is also possible by MALDI-IM-TOFMS.
      Ion signals corresponding to nucleobase losses, w-type, and y-type fragments were
      identified by use of differences in ion mobility. MALDI-IM-TOFMS was also used to
      resolve DNA-platinum adducts from the corresponding unmodified oligonucleotides.

PMID- 12185574
TI  - Ligand and metal-ion effects in metal-ion clusters used for chiral analysis of
      alpha-hydroxy acids by the kinetic method.
AB  - Chiral recognition of alpha-hydroxy acids has been achieved, and mixtures of
      enantiomers have been quantified in the gas phase, by using the kinetics of
      competitive unimolecular dissociation of singly-charged transition metal ion
      bound trimeric complexes, [M(II)(A)(ref*)(2)-H](+) (M(II)=divalent transition
      metal ion; A=alpha-hydroxy acid; ref*=chiral reference ligand), to form the
      dimeric complexes [M(II)(A)(ref*)-H](+) and [M(II)(ref*)(2)-H](+). Chiral
      selectivity, the ratio of these two fragment ion abundances for the complex
      containing the analyte in one enantiomeric form expressed relative to that for
      the fragments of the corresponding complex containing the other enantiomer,
      ranges from 0.65 to 7.32. Chiral differentiation is highly dependent on the
      choice of chiral reference compound and central metal ion. The different
      coordination geometry of complexes resulting from the different d-orbital
      electronic configurations of these transition metal ions plays a role in chiral
      discrimination. Of all the transition metal ions examined chiral recognition is
      lowest for Cu(II), because of large distortion of the coordination complexes, and
      hence weak metal-ligand interactions and small stereochemical effects. It seems
      that two independent pi-cation interactions occur when N-acetyl-substituted
      aromatic amino acids used as the reference ligands and this accounts for improved
      chiral discrimination. If both metal-ligand and ligand-ligand interactions are
      optimized, large chiral selectivity is achieved. The sensitive nature of the
      methodology and the linear relationship between the logarithm of the fragment ion
      abundance ratio and the optical purity, which are intrinsic to the kinetic
      method, enable mixtures to be analyzed for small enantiomeric excess ( ee) by
      simply recording the ratios of fragment ion abundances in a tandem mass spectrum.

PMID- 12185575
TI  - The use of neutral cyclodextrins as additives in capillary electrophoresis for
      the separation and identification of propoxyphene enantiomers.
AB  - A simple, efficient, and rapid method is described for separation of the
      enantiomers of propoxyphene by capillary electrophoresis with neutral
      cyclodextrins as chiral separators. This method has several advantages over the
      crystallization method employed by some forensic laboratories, including
      unambiguous results, ease of use, and smaller sample-size requirement. The method
      enables baseline separation of the propoxyphene enantiomers in approximately six
      minutes, which is less than one-third of the time required for a previously
      published method.

PMID- 12185577
TI  - Application of infrared spectroscopy to monitoring gas insulated high-voltage
      equipment: electrode material-dependent SF(6) decomposition.
AB  - Sulfur hexafluoride is a chemically inert gas which is used in gas insulated
      substations (GIS) and other high-voltage equipment, leading to a significant
      enhancement of apparatus lifetime and reductions in installation size and
      maintenance requirements compared to conventional air insulated substations.
      However, component failures due to aging of the gas through electrical discharges
      may occur, and on-site monitoring for risk assessment is needed. Infrared
      spectroscopy was used for the analysis of gaseous by-products generated from
      electrical discharges in sulfur hexafluoride gas. An infrared monitoring system
      was developed using a micro-cell coupled to an FTIR spectrometer by silver halide
      fibers. Partial least-squares calibration was applied by using a limited number
      of optimally selected spectral variables. Emphasis was placed on the
      determination of main decomposition products, such as SOF(2), SOF(4), and
      SO(2)F(2). Besides the different electrical conditions, the material of the plane
      counter electrode of the discharge chamber was also varied between silver,
      aluminum, copper, tungsten, or tungsten/copper alloy. For the spark experiments
      the point electrode was the same material as chosen for the plane electrode,
      whereas for partial discharges a stainless steel needle was employed.
      Complementary investigations on the chemical composition within the solid counter
      electrode material by secondary neutral mass spectrometry (SNMS) were also
      carried out. Under sparking conditions, the electrode material plays an important
      role in the decomposition rates of the gas-phase, but no relevant material
      dependence could be observed under partial discharge conditions.

PMID- 12185576
TI  - Polymerized crystalline colloidal array chemical-sensing materials for detection
      of lead in body fluids.
AB  - We have developed intelligent polymerized crystalline colloidal array (IPCCA)
      chemical-sensing materials for detection of Pb(2+) in high ionic-strength
      environments such as body fluids with a detection limit of <500 nmol L(-1) Pb(2+)
      (100 ppb). This IPCCA lead sensor consists of a mesoscopically periodic array of
      colloidal particles polymerized into an acrylamide hydrogel. The array Bragg
      diffracts light in the visible spectral region because of the periodic spacing of
      the colloidal particles. This material also contains a crown ether chelating
      agent for Pb(2+). Chelation of Pb(2+) by the IPCCA in low-ionic-strength
      solutions results in a Donnan potential that swells the gel, which red-shifts the
      diffracted light in proportion to the Pb(2+) concentration. At high ionic
      strength the Donnan potential is, unfortunately, swamped and no static response
      occurs for these sensors. We demonstrate, however, that we can determine Pb(2+)
      at high ionic strength by incubating these IPCCA in a sample solution and then
      measuring their transient response on exposure to pure water. The non-complexed
      ions diffuse from the IPCCA faster than the bound Pb(2+). The resulting transient
      IPCCA diffraction red-shift is proportional to the concentration of Pb(2+) in the
      sample. These IPCCA sensors can thus be used as sensing materials in optrodes to
      determine Pb(2+) in high-ionic-strength solutions such as body fluids.

PMID- 12185578
TI  - PDMS-chemistry of angiotensin II and insulin in glucose glass thin films.
AB  - A plasma desorption mass spectrometry study was made on the properties of glucose
      and glucose/glucuronic acid thin films as matrices for amino acids, small and
      large peptides and insulin. Amino acids and small peptides are distributed
      throughout the film as it is formed from aqueous solutions and the mass spectra
      are similar to what is observed for nitrocellulose matrices. AngiotensinII
      (angII), insulin, and reduced insulin containing the separated A- and B-chains
      concentrate at the surface of the film due to the hydrophobic interaction.
      Extensive positive and negative fragmentation patterns are observed for angII
      using the glucose glass film. The fragment ions appear to be formed from layers
      just below the surface of the film. The co-matrix of glucuronic acid/glucose
      produces a higher molecular ion yield. The spectrum of insulin in glucuronic
      acid/glucose consists mainly of positive ions with a fragmentation pattern from
      the B-chain. The spectrum of reduced insulin using a nitrocellulose matrix gives
      B-chain ions but glucose/glucuronic acid gives A-chain ions in both the positive
      and negative ion spectra. The fragmentation patterns of the A-chain and B-chain
      ions are sensitive to the nature of the matrix. An extensive negative ion A-chain
      fragmentation pattern was observed with glutamate ions serving as the charge
      centers. The reasons for the behavior of the A- and B-chain fragmentation
      patterns in these matrices is not clear.

PMID- 12185579
TI  - Radio frequency glow discharge optical emission spectroscopy: a new weapon in the
      depth profiling arsenal.
AB  - While the array of analytical methods routinely applied for depth profile
      analysis was fairly static over the decades of the 1980s and 1990s, there appears
      to be an emerging technique that has a number of very positive and complementary
      attributes, and warrants serious consideration by the thin film community. Radio
      frequency glow discharge optical emission spectroscopy (rf-GD-OES) is a technique
      that provides depth-resolved elemental composition information on a wide variety
      of sample types. In a manner very much like most depth profiling methods, the rf
      GD plasma utilizes an ion sputtering step to ablate sample material in a layer-by
      layer fashion. Different from the more commonly applied methods, the device
      operates at elevated pressures [2-10 Torr Ar (266-1,330 Pa)] and has the inherent
      capability of sputtering electrically insulating materials directly, without any
      auxiliary means of charge compensation. In addition, sputtering rates on the
      order of 1 micro m/min provide rapid analysis, with depth resolving powers that
      are comparable to high-vacuum sputtering methods. Three examples of the use of
      the rf-GD-OES method are presented as examples of its analytical potential: (1)
      boron-implanted silicon wafer, (2) a barrier-type alumina film, and (3) a porous
      type alumina film. It is believed that the method holds a great deal of promise
      as part of the arsenal of weapons in the thin films laboratory.

PMID- 12185580
TI  - A study of method robustness for arsenic speciation in drinking water samples by
      anion exchange HPLC-ICP-MS.
AB  - Regulating arsenic species in drinking waters is a reasonable objective, since
      the various species have different toxicological impacts. However, developing
      robust and sensitive speciation methods is mandatory prior to any such
      regulations. Numerous arsenic speciation publications exist, but the question of
      robustness or ruggedness for a regulatory method has not been fully explored. The
      present work illustrates the use of anion exchange chromatography coupled to ICP
      MS with a commercially available "speciation kit" option. The mobile phase
      containing 2 mM NaH(2)PO(4) and 0.2 mM EDTA at pH 6 allowed adequate separation
      of four As species (As(III), As(V), MMAA, DMAA) in less than 10 min. The
      analytical performance characteristics studied, including method detection limits
      (lower than 100 ng L(-1) for all the species evaluated), proved the suitability
      of the method to fulfill the current regulation. Other parameters evaluated such
      as laboratory fortified blanks, spiked recoveries, and reproducibility over a
      certain period of time produced adequate results. The samples analyzed were taken
      from water utilities in different areas of the United States and were provided by
      the U.S. EPA. The data suggests the speciation setup performs to U.S. EPA
      specifications but sample treatment and chemistry are also important factors for
      achieving good recoveries for samples spiked with As(III) as arsenite and As(V)
      as arsenate.

PMID- 12185582
TI  - TIP49, but not TRRAP, modulates c-Myc and E2F1 dependent apoptosis.
AB  - We previously described two nuclear cofactors, TRRAP and TIP49, that have
      functional roles in Myc-mediated oncogenesis. We have now expanded the analysis
      of these Myc-associated cofactors to investigate their roles in apoptosis and
      cell proliferation. Although TRRAP and TIP49 are both essential for
      transformation, TIP49 modulates c-Myc-mediated apoptosis whereas disruption of
      TRRAP activity has no apparent effect on apoptosis. We extended our analysis of
      TIP49 to show that it also binds to the E2F1 transactivation domain and modulates
      both transforming and apoptotic activities. These results indicate that
      individual cofactors differentially potentiate c-Myc and E2F1 functions.

PMID- 12185581
TI  - Activation of anaplastic lymphoma kinase is responsible for hyperphosphorylation
      of ShcC in neuroblastoma cell lines.
AB  - Shc family of docking proteins, ShcA, ShcB and ShcC, play roles in cellular
      signal transduction by binding to phosphotyrosine residues of various activated
      receptor tyrosine kinases. Both ShcB and ShcC proteins are selectively expressed
      in the neural system of adult mouse tissues. In most of neuroblastoma cells,
      obvious tyrosine phosphorylation of ShcC was observed, whereas expression of ShcB
      was considerably low. Phosphoproteins associated with hyperphosphorylated ShcC
      were purified from neuroblastoma cell lines, and identified by mass-spectrometry.
      Anaplastic lymphoma kinase (ALK), which turned out to be one of these
      phosphoproteins, was constitutively activated and associated with the PTB domain
      of ShcC in three neuroblastoma cells. In vitro kinase assay revealed that ShcC is
      a potent substrate of the activated ALK kinase. The ALK gene locus was
      significantly amplified in both of these cell lines, suggesting that gene
      amplification leads to constitutive activation of the ALK kinase, which results
      in hyperphosphorylation of ShcC. Constitutive activation of ALK appeared to
      interfere with signals from other receptor tyrosine kinases. ALK-ShcC signal
      activation, possibly caused by co-amplification with the N-myc gene, might give
      additional effects on malignant tumor progression of neuroblastoma.

PMID- 12185583
TI  - DNA damage, death receptor activation and reactive oxygen species contribute to
      ultraviolet radiation-induced apoptosis in an essential and independent way.
AB  - Nuclear DNA damage and death receptor (CD95) activation by ultraviolet-B
      radiation (UVB) play a major role in UVB-induced apoptosis. Removal of DNA damage
      combined with inhibition of death receptor activation resulted in pronounced but
      not complete suppression of apoptosis, indicating that a third independent
      pathway is involved. Since reactive oxygen species (ROS) cause apoptosis and are
      induced by UVB, the radical scavenger pyrrolidene-dithiocarbamate (PDTC) was
      used. PDTC prevented UVB-induced apoptosis partially, H(2)O(2)-induced cell death
      largely, but not CD95-mediated apoptosis. The same was observed for cytochrome c
      release from mitochondria, another important event during apoptosis. The
      proapoptotic protein Bid was cleaved upon exposure to UVB or to agonistic anti
      CD95-antibodies, but not to H(2)O(2), indicating that H(2)O(2) uses a different
      pathway. The fact that PDTC neither inhibited CD95-mediated apoptosis nor
      affected UV-induced DNA damage indicated that ROS generated during UVB
      irradiation may directly trigger mitochondrial cytochrome c release, thereby
      contributing to apoptosis. Accordingly, complete inhibition of apoptosis was
      observed when in addition to DNA damage removal via photoreactivation and
      blockade of CD95 signaling by caspase-8 inhibitor zIETD, PDTC was added before
      UVB exposure. This indicates that DNA damage, death receptor activation and ROS
      formation contribute to UVB-induced apoptosis in an essential and independent
      way.

PMID- 12185585
TI  - Identification of membrane-type matrix metalloproteinase-1 as a target of the
      beta-catenin/Tcf4 complex in human colorectal cancers.
AB  - Genetic alterations of APC and CTNNB1 (beta-catenin) have been identified in a
      number of human cancers including tumors arising in the colon and liver.
      Mutations in these genes lead to abnormal accumulation of beta-catenin and
      constitutive activation of target genes in the Wnt signaling pathway. To clarify
      the precise role of accumulated beta-catenin in colorectal carcinogenesis, we
      searched for genes involved in the beta-catenin/Tcf signaling pathway by cDNA
      microarray. MT1-MMP (membrane-type matrix metalloproteinase) was among 84 genes
      that were down-regulated after beta-catenin had been depleted by transduction of
      wild-type APC in SW480 cells. Expression of MT1-MMP was elevated in 22 of 24
      colon carcinomas we examined. Reporter assays and an electromobility-shift assay
      revealed a DNA fragment between -1169 bp and -1163 bp in the 5' flanking region
      of this gene to be a target of the beta-catenin/Tcf4 complex. Our results
      indicate that MT1-MMP is a direct down-stream target in the Wnt signaling
      pathway, and that one of the ways accumulated beta-catenin contributes to
      colorectal carcinogenesis is by transactivating this gene.

PMID- 12185584
TI  - Rho-kinase contributes to diphosphorylation of myosin II regulatory light chain
      in nonmuscle cells.
AB  - Phosphorylation of myosin II regulatory light chain (MRLC) is important for cell
      motility and cytokinesis in nonmuscle cells. Although the regulation of
      monophosphorylated MRLC at serine 19 throughout the cell cycle was examined in
      detail, MRLC diphosphorylation at both threonine 18 and serine 19 is still
      unclear. Here we found that Rho-kinase has an activity for MRLC diphosphorylation
      in nonmuscle cells using sequential column chromatographies. Transfection of Rho
      kinase-EGFP induced the excess diphosphorylated MRLC and the bundling of the
      actin filaments. Conversely, the treatment of cells with a specific inhibitor of
      Rho-kinase, Y-27632, resulted in the decrease of endogenous diphosphorylated MRLC
      and actin stress fibers. Immunolocalization studies showed that both
      diphosphorylated MRLC and Rho-kinase accumulated and colocalized at the
      contractile ring and the midbody in dividing cells. Taken together, it is
      suggested that Rho-kinase contributes to MRLC diphosphorylation and
      reorganization of actin filaments in nonmuscle cells.

PMID- 12185586
TI  - Phosphatidylinositol-3 kinase inhibitors enhance the anti-leukemia effect of
      STI571.
AB  - BCR/ABL fusion tyrosine kinase is responsible for the initiation and maintenance
      of the Philadelphia chromosome (Ph(1))-positive chronic myelogenous leukemia
      (CML) and a cohort of acute lymphocytic leukemias (ALL). STI571 (Gleevec), a
      novel anti-leukemia drug targeting BCR/ABL kinase can induce remissions of the
      Ph(1)-positive leukemias. STI571 was recently combined with the standard
      cytostatic drugs to achieve better therapeutic results and to overcome emerging
      drug resistance mechanisms. We decided to search for a more specific partner
      compound for STI571. Our previous studies showed that a signaling protein
      phosphatidylinositol-3 kinase (PI-3k) is essential for the growth of CML cells,
      but not of normal hematopoietic cells (Blood, 86:726,1995). Therefore the anti-
      Ph(1)-leukemia effect of the combination of BCR/ABL kinase inhibitor STI571 and
      PI-3k inhibitor wortmannin (WT) or LY294002 (LY) was tested. We showed that
      STI571+WT exerted a synergistic effect against the Ph(1)-positive cell lines, but
      did not affect the growth of Ph(1)-negative cell line. Moreover, the combinations
      of STI571+WT or STI571+LY were effective in the inhibition of clonogenic growth
      of CML-chronic phase and CML-blast crisis patient cells, while sparing normal
      bone marrow cells. Single colony RT-PCR assay showed that colonies arising from
      the mixture of CML cells and normal bone marrow cells after treatment with
      STI571+WT were selectively depleted of BCR/ABL-positive cells. Biochemical
      analysis of the CML cells after the treatment revealed that combination of
      STI571+WT caused a more pronounced activation of caspase-3 and induced massive
      apoptosis, in comparison to STI571 and WT alone. In conclusion, combination of
      STI571+WT or STI571+LY may represent a novel approach against the Ph(1)-positive
      leukemias.

PMID- 12185588
TI  - Proapoptotic and redox state-related signaling of reactive oxygen species
      generated by transformed fibroblasts.
AB  - Oncogenic transformed fibroblasts are characterized by extracellular superoxide
      anion generation through a membrane-associated NADPH oxidase. After cellular
      glutathione depletion, extracellular reactive oxygen species (ROS) generated by
      transformed fibroblasts exhibit a strong apoptosis-inducing potential. As
      apoptosis induction under glutathione depletion is inhibited by catalase, the
      NADPH oxidase inhibitor apocynin, superoxide dismutase, the hydroxyl radical
      scavenger terephthalate and the iron chelator deferoxamine, the metal-catalysed
      Haber-Weiss reaction seems to be the responsible signaling mechanism. In contrast
      to extracellular ROS, intracellular ROS play no role for apoptosis induction in
      glutathione-depleted transformed fibroblasts initially, since a high level of
      intracellular catalase scavenges intracellular hydrogen peroxide. Intracellular
      catalase seems to be induced by extracellular hydrogen peroxide, as pretreatment
      of transformed fibroblasts with exogenous catalase downmodulates endogenous
      catalase and renders glutathione-depleted transformed cells susceptible for the
      effect of endogenous hydrogen peroxide. In contrast to transformed fibroblasts,
      nontransformed glutathione-depleted fibroblasts do not generate substantial
      extracellular ROS, but apoptosis is efficiently induced in these cells by
      intracellular ROS. Our data show that extracellular ROS of transformed
      fibroblasts exhibit redox-related signaling and at the same time represent a
      potential apoptosis-inducing hazard through the metal-catalysed Haber-Weiss
      reaction.

PMID- 12185587
TI  - Functional interaction between human papillomavirus type 18 E2 and poly(ADP
      ribose) polymerase 1.
AB  - Human papillomavirus E2 protein is a transcription factor of viral gene
      expression and DNA replication. Here we show that PARP is a positive regulator of
      the E2 protein of human papillomavirus type 18 (HPV-18). PARP interacted with the
      COOH terminal region of HPV-18 E2 in vitro. The E2 interaction domain within PARP
      is located in the NH(2)-terminal zinc finger motif and the BRCT motif included in
      the automodification domain. Overexpression of either wild type or the NH(2)
      terminal region of PARP containing zinc finger and BRCT stimulated E2-dependent
      transcription. Gel retardation assay indicates that PARP augments DNA binding
      activity of E2 in vitro. We also show that PARP-1 is recruited to E2-dependent
      promoter in vivo using ChIP assay. These results suggest that PARP serves a
      transcriptional co-activator in E2-dependent transcription by interacting
      directly with the HPV E2 protein.

PMID- 12185590
TI  - Target disruption of the mutant beta-catenin gene in colon cancer cell line
      HCT116: preservation of its malignant phenotype.
AB  - Most colorectal carcinomas harbor genetic alterations that result in
      stabilization of beta-catenin. A colorectal carcinoma cell line, HCT116, which
      has both mutated and wild-type beta-catenin genes, was engineered by homologous
      recombination to investigate the significance of beta-catenin gene mutation. As
      expected, the mutant allele-targeted clones showed decreased beta-catenin
      expression and downregulation of T-cell factor (TCF)/lymphoid enhancer factor
      (LEF)-dependent transcription. Morphologically, targeted clones were only
      minimally altered under usual culture conditions, but under low serum conditions,
      mutant allele-targeted clones still grew in plane, in contrast to parental cell
      line and wild allele-targeted clones, which formed spheroids. The mutant allele
      targeted clones showed no significant changes in growth rate and anchorage
      independent growth in vitro, and displayed rather increased growth in vivo.
      Although beta-catenin stabilization affects some biological characteristics
      including adhesive properties, it may not have growth-promoting effects at least
      in some colorectal carcinomas.

PMID- 12185591
TI  - Long-patch base excision repair of apurinic/apyrimidinic site DNA is decreased in
      mouse embryonic fibroblast cell lines treated with plumbagin: involvement of
      cyclin-dependent kinase inhibitor p21Waf-1/Cip-1.
AB  - Molecular interactions among cell cycle and DNA repair proteins have been
      described, but the impact of many of these interactions on cell cycle control and
      DNA repair remains unclear. The cyclin-dependent kinase inhibitor, p21, is known
      to be involved in DNA damage-induced cell cycle arrest and blocking DNA
      replication and repair. Participation of p21 has been implicated in nucleotide
      excision repair. However, the role of p21 in the base excision repair (BER)
      pathway has not been thoroughly studied. In the present investigation, we treated
      isogenic mouse embryonic fibroblast (MEF) cell lines containing wild-type (MEF
      polbeta) or DNA polymerase beta (polbeta) gene-knockout (MEFpolbetaKO) with
      oxidative DNA-damaging agent, plumbagin, and examined its effect on p21 levels
      and BER activity. Plumbagin treatment caused a S-G(2)/M phase arrest and cell
      death of both MEF cell lines, induced p21 levels, and decreased p21-mediated long
      patch (LP) BER by blocking DNA ligase activity in the polbeta-dependent pathway
      and by blocking both FEN1 and DNA ligase activity in polbeta-independent pathway.
      These findings suggest that plumbagin induced p21 levels play a regulatory role
      in cell cycle arrest, apoptosis, and polbeta-dependent and -independent LP-BER
      pathways in MEF cells.

PMID- 12185589
TI  - pRb2/p130 promotes radiation-induced cell death in the glioblastoma cell line
      HJC12 by p73 upregulation and Bcl-2 downregulation.
AB  - This study shows that in the glioblastoma hamster cell line HJC12 the
      retinoblastoma family member pRb2/p130 enhances gamma-radiation-induced cell
      death. In HJC12 cells the tetracycline-regulated expression of pRb2/p130
      increased the percentage of gamma-radiation-induced apoptotic cells from 27 to
      47%. pRb2/p130 overexpression was associated with the downregulation of the anti
      apoptotic factor Bcl-2 and the upregulation of the steady-state protein levels of
      the pro-apoptotic transcription factor p73. In particular, RT-PCR showed a
      significant increase in the expression of the p73delta isoform when pRb2/p130 was
      overexpressed. The ability of pRb2/p130 to modulate apoptosis was not associated
      with its role in mediating G0/G1 arrest during cell cycle progression. Our data
      suggest a role for pRb2/p130 in glioblastoma gamma-radiation-induced cell death,
      indicating that the antitumoral action of pRb2/p130 can regulate both inhibition
      of cell cycle progression and induction of cell death.

PMID- 12185592
TI  - Dominant negative MEKK1 inhibits survival of pancreatic cancer cells.
AB  - Human pancreatic cancers harbor mutations in the K-ras gene, and these mutations
      convert the gene oncogenic and constitutively active forms. However, in
      pancreatic cancer cells little is known about the activation of the downstream
      pathways of Ras, MEK-ERK and MEKK1-JNK, and their roles in cell survival and
      proliferation. An analysis of nine pancreatic cancer tissues revealed JNK
      activation in all tumor samples and ERK activation in three tumor samples. Colony
      formation assays by transfection of dominant negative mutants of Ras, ERK or
      MEKK1 into pancreatic cancer cell lines (BxPC-3, PANC-1, MIAPaCa-2 and AsPC-1)
      and an amnion-derived cell line (FL) revealed that DN-MEKK strongly inhibits the
      survival of colonies in pancreatic cancer cells, but not in FL cells. In vitro
      kinase assays and luciferase assays using the Gal4c-Jun system revealed that in
      pancreatic cancer cells DN-MEKK fails to inhibit JNK activation. In PANC-1 cells,
      c-Jun was found to be a major component of protein component binding to AP-1 site
      and CRE, but not in FL cells. The inhibitory effect of DN-MEKK in PANC-1 cells
      was thought to be the result of the inhibition of c-Jun DNA-binding. The
      difference of suppression in pancreatic cancer cells and non-pancreatic cancer
      cells suggested that the MEKK1 pathway mainly contributes to cell survival in
      pancreatic cancer cells and may provide an advantage for the gene therapy of
      pancreatic cancers using DN-MEKK expression vectors.

PMID- 12185593
TI  - Wild-type p53 inhibits replication-associated homologous recombination.
AB  - In mammalian cells homologous recombination is stimulated, when the replication
      fork stalls at DNA breaks or unrepaired lesions. The tumor suppressor p53
      downregulates homologous recombination independently of its transcriptional
      transactivation function and has been linked to enzymes of DNA recombination and
      replication. To study recombination with respect to replication, we utilized a
      SV40 virus based assay, to follow the synchronous events after primate cell
      infection. gamma-ray treatment at different times after viral entry unveiled an
      increase of interchromosomal exchange frequencies, when the damage was introduced
      during DNA synthesis. Elevated recombination frequencies were fully suppressed by
      p53. With respect to the downregulation of spontaneous recombination, we noticed
      a requirement for active p53 molecules, when replication started. After a
      transient treatment with replication inhibitors, we observed inhibition of the
      drug induced recombination by p53, particularly for the elongation inhibitor
      aphidicolin. Consequently, we propose that p53 is a surveillance factor of
      homologous recombination at replication forks, when they stall as a consequence
      of endogenous or of exogenously introduced damage.

PMID- 12185594
TI  - The ability to engage enterocyte apoptosis does not predict long-term crypt
      survival in p53 and Msh2 deficient mice.
AB  - Apoptosis and long term enterocyte survival were examined in vivo after exposure
      to three cytotoxic agents (Cisplatin, Nitrogen Mustard and N-methyl-N-nitrosourea
      (NMNU/MNU)) within mice either singly or doubly mutant for p53 and Msh2. P53
      deficiency caused abrogation of the immediate apoptotic response to each agent,
      but only led to increased survival after cisplatin treatment. Msh2 deficiency
      reduced the apoptotic response to each agent, but only led to increased crypt
      survival after NMNU treatment. Following cisplatin treatment, the response of
      (Msh2(-/-), p53(-/-)) mice paralleled that of the p53(-/-) mice. A delayed wave
      of apoptosis was observed in both p53(-/-) and (Msh2(-/-), p53(-/-)) mice
      demonstrating this phenomenon to be independent of functional Mismatch repair
      (MMR). We conclude that loss of either p53 or Msh2 dependent apoptosis does not
      predict long-term crypt survival in vivo, however genetic status clearly can
      modulate survival for some agents such as cisplatin.

PMID- 12185595
TI  - The DNA repair protein, O(6)-methylguanine-DNA methyltransferase is a proteolytic
      target for the E6 human papillomavirus oncoprotein.
AB  - We have previously shown that O(6)-methylguanine-DNA methyltransferase (MGMT), a
      DNA repair protein that protects tissues against toxic and carcinogenic effects
      of alkylating agents, is degraded through ubiquitination-dependent proteolysis.
      Here, we investigated the role of the human papillomavirus (HPV) E6 protein in
      MGMT degradation. In three pairs of isogenic human tumor cell lines in which a
      member of each pair expressed the E6 protein through stable transfection
      (HCT116/HCT116-E6, MCF7/MCF7-E6, and RKO/RKO-E6), we found a consistent 40-55%
      reduction in the MGMT protein level and its activity in all E6-expressing cells
      compared with the parent cells (P=<0.05). E6 expression did not, however, alter
      the levels of MGMT mRNA. Addition of the recombinant MGMT (rMGMT) protein to
      extracts of HCT116/E6 cells resulted in the binding of E6 to MGMT. Further, the
      purified E6 protein promoted the degradation of rMGMT in rabbit reticulocyte
      lysates. Immunoprecipitation assays showed the presence of a ternary protein
      complex between MGMT, E6, and the cellular ubiquitin-ligase E6-associated protein
      (E6-AP). Transient transfection of the p53-null H1299 lung tumor cells with an E6
      construct also down-regulated the MGMT. The MGMT protein also showed structural
      features that are compatible for interaction with the E6, and E6-AP components.
      Collectively, these data suggest that the oncogenic E6 proteins enhance the
      ubiquitin-dependent proteolysis of MGMT.

PMID- 12185596
TI  - Identification of serum anti-human telomerase reverse transcriptase (hTERT) auto
      antibodies during progression to hepatocellular carcinoma.
AB  - Human telomerase reverse transcriptase, hTERT, is the catalytic component of
      human telomerase. Expression of hTERT confers telomerase activity, indicating
      that hTERT is the rate-limiting component of human telomerase. Here we report the
      detection of anti-hTERT auto-antibodies in the sera derived patients with
      hepatocellular carcinoma using recombinant, purified hTERT as an antigen in an
      enzyme linked immunosorbent assay (ELISA). The levels of anti-hTERT antibodies in
      serum correlated with progression to hepatocellular carcinoma. In contrast, we
      detected only low levels of anti-hTERT auto-antibodies in the sera derived from
      18 normal volunteers. The observation of hTERT auto-antibodies in the sera
      derived from cancer patients suggests that such auto-antibodies constitute novel
      and specific tumor marker.

PMID- 12185597
TI  - Cathepsin-D affects multiple tumor progression steps in vivo: proliferation,
      angiogenesis and apoptosis.
AB  - Cathepsin-D is an independent marker of poor prognosis in human breast cancer. We
      previously showed that human wild-type cathepsin-D, as well as its mutated form
      devoid of proteolytic activity stably transfected in 3Y1-Ad12 cancer cells,
      stimulated tumor growth. To investigate the mechanisms by which human cathepsin-D
      and its catalytically-inactive counterpart promoted tumor growth in vivo, we
      quantified the expression of proliferating cell nuclear antigen, the number of
      blood vessels and of apoptotic cells in 3Y1-Ad12 tumor xenografts. We first
      verified that both human wild-type and mutated cathepsin-D were expressed at a
      high level in cathepsin-D xenografts, whereas no human cathepsin-D was detected
      in control xenografts. Our immunohistochemical studies then revealed that both
      wild-type cathepsin-D and catalytically-inactive cathepsin-D, increased
      proliferating cell nuclear antigen expression and tumor angiogenesis.
      Interestingly, wild-type cathepsin-D significantly inhibited tumor apoptosis,
      whereas catalytically-inactive cathepsin-D did not. We therefore propose that
      human cathepsin-D stimulates tumor growth by acting-directly or indirectly-as a
      mitogenic factor on both cancer and endothelial cells independently of its
      catalytic activity. Our overall results provide the first mechanistic evidences
      on the essential role of cathepsin-D at multiple tumor progression steps,
      affecting cell proliferation, angiogenesis and apoptosis.

PMID- 12185598
TI  - Rare mutations of the DMBT1 gene in human astrocytic gliomas.
AB  - The Deleted in Malignant Brain Tumors 1 gene (DMBT1) has been proposed as a tumor
      suppressor gene candidate in human brain tumors, based on the observation of
      homozygous deletions affecting the DMBT1 region or part of the gene. In order to
      support this hypothesis, we performed a mutational analysis of the entire coding
      region of DMBT1, employing SSCP analysis and direct DNA sequencing in a series of
      79 astrocytic gliomas. Five somatic mutations were detected. Two mutations, one
      of which resulted in an amino acid exchange, occurred in glioblastomas. One
      pilocytic astrocytoma carried two missense mutations and another pilocytic
      astrocytoma contained a somatic mutation, not affecting the presumed protein. In
      addition, 21 of the 27 single nucleotide polymorphisms identified in this study
      have not been recognized previously. The data indicate, that small mutations are
      not a frequent finding in gliomas.

PMID- 12185599
TI  - A strong candidate gene for the Papg1 locus on mouse chromosome 4 affecting lung
      tumor progression.
AB  - Lung cancer is the leading cause of cancer death among both men and women,
      accounting for more than 28% of all cancer deaths. In fact, more people die of
      lung cancer than of colon, breast, and prostate cancers combined. Although lung
      cancer is largely induced by smoking, there is strong evidence for genetic
      susceptibility and gene-environment interactions in the development of lung
      cancer. Inbred mouse models offer an effective means of identifying candidate
      lung cancer susceptibility loci since genetic heterogeneity and enormous
      variation in exposure levels to environmental agents make it difficult to
      identify lung cancer susceptibility loci in humans. Papg-1 (pulmonary adenoma
      progression 1) was previously mapped to a region on mouse chromosome 4. This
      locus contains a candidate gene, Cdkn2a also referred to as Ink4a/Arf, which
      dually encodes two established tumor suppressors p16(INK4a) and ARF. Cdkn2a
      became a primary candidate for Papg-1 for two reasons: (1) two haplotypes of
      mouse Cdkn2a were found to segregate with differential genetic susceptibility to
      lung tumor progression in mice; and (2) in vitro studies showed that the
      p16(INK4a) allele from the BALB/cJ mouse had a significantly decreased ability to
      bind and inhibit CDK6 and to suppress cell growth when compared with the
      p16(INK4a) allele from the A/J mouse. Here, we report that mice with a
      heterozygous deficiency for the A/J Cdkn2a allele were significantly more
      susceptible to lung tumor progression than mice with a heterozygous deficiency
      for a BALB/cJ Cdkn2a allele, when compared to their respective wild type mice.
      These results offer strong evidence that naturally occurring variation of
      p16(INK4a) influences susceptibility to enhance lung tumor progression making it
      a strong candidate for the lung tumor progression locus, Papg-1.

PMID- 12185600
TI  - WAVE3, an actin-polymerization gene, is truncated and inactivated as a result of
      a constitutional t(1;13)(q21;q12) chromosome translocation in a patient with
      ganglioneuroblastoma.
AB  - Neuroblastoma (Nb) is a malignancy of the sympathetic nervous system which
      affects children in their first decade. It is the most common extra-cranial solid
      tumor in children with an incidence of approximately 1 in 8-10 000 live births
      annually and accounts for approximately 10% of all children's cancers.
      Ganglioneuroblastoma is a relatively benign form of Nb and consists of a mixture
      of fibrils, mature and maturing ganglion cells, as well as undifferentiated
      neuroblasts. During routine cytogenetic analysis of patients with different
      manifestations of neuroblastoma we have identified one patient with
      ganglioneuroblastoma that carries an apparently balanced t(1:13)(q21:q12)
      reciprocal translocation. Positional cloning of the translocation breakpoint on
      chromosome 13 resulted in the mapping of the breakpoint between coding exon 2 and
      exon 3 of WAVE3, a member of WASP gene family. Although the breakpoint region on
      chromosome 1 was localized to within 2 kb of genomic sequence, no gene was found
      to be interrupted on this chromosome. The WAVE3 transcript is mainly expressed in
      the nervous system and, like all the members of the WASP gene family, WAVE3 is a
      key element in actin polymerization and cytoskeleton organization. WAVE3,
      therefore, is important for cell differentiation and motility and its expression
      is lost in a number of low grade and stage 4S tumors. From analysis of its
      expression pattern and function, WAVE3 is a candidate tumor suppressor gene, at
      least in some forms of neuroblastoma.

PMID- 12185601
TI  - Two novel tumor suppressor gene loci on chromosome 6q and 15q in human
      osteosarcoma identified through comparative study of allelic imbalances in mouse
      and man.
AB  - We have performed a comparative study of allelic imbalances in human and murine
      osteosarcomas to identify genetic changes critical for osteosarcomagenesis. Two
      adjacent but discrete loci on mouse chromosome 9 were found to show high levels
      of allelic imbalance in radiation-induced osteosarcomas arising in
      (BALB/cxCBA/CA) F1 hybrid mice. The syntenic human chromosomal regions were
      investigated in 42 sporadic human osteosarcomas. For the distal locus (OSS1) on
      mouse chromosome 9 the syntenic human locus was identified on chromosome 6q14 and
      showed allelic imbalance in 77% of the cases. Comparison between the human and
      mouse syntenic regions narrowed the locus down to a 4 Mbp fragment flanked by the
      marker genes ME1 and SCL35A1. For the proximal locus (OSS2) on mouse chromosome
      9, a candidate human locus was mapped to chromosome 15q21 in a region showing
      allelic imbalance in 58% of human osteosarcomas. We have used a combination of
      synteny and microsatellite mapping to identify two potential osteosarcoma
      suppressor gene loci. This strategy represents a powerful tool for the
      identification of new genes important for the formation of human tumors.

PMID- 12185602
TI  - Sacral root stimulation.

PMID- 12185603
TI  - Intermittent catheterization: which is the optimal technique?
AB  - STUDY DESIGN: Literature review to evaluate the practical techniques used for
      intermittent catheterization (IC) and intermittent self-catheterization (ISC).
      OBJECTIVES: To ascertain the requirements for proper IC and ISC. To evaluate if a
      best technique exists. METHODS: Relevant articles on the subject are reviewed.
      CONCLUSION: There is a wide variety of materials and techniques applied for IC
      and ISC. This does not seem to change the practical outcome much if the basic
      principles are used: good education and training, clean and atraumatic technique,
      good patient compliance in the long-term. There is neither one best technique nor
      one best material for IC. Both depend greatly on the patient's individual
      anatomic, social and economic state.

PMID- 12185604
TI  - Intracranial dural arteriovenous fistula causing a myelopathy.

PMID- 12185605
TI  - Neurogenic bladder management and cutaneous non-continent ileal conduit.
AB  - STUDY DESIGN: Prospective monocentric follow-up study. OBJECTIVES: To assess the
      results of cutaneous non-continent diversion for neurogenic bladder management.
      SETTINGS: Department of Urology (Pitie-Salpetriere Hospital), Department of
      Neurological Rehabilitation (Raymond Poincare Hospital), Assistance Publique
      Hopitaux de Paris, University Paris VI and V. METHODS: We reviewed the charts of
      33 consecutive patients (19 women, 14 men), operated between 1979 and 1999.
      Twenty-one patients had spinal cord injury (SCI), four had multiple sclerosis,
      three had various forms of myelitis and five had central neurological diseases.
      Diversion was indicated for upper urinary tract protection (17), perineal dryness
      (14) and/or functional or social reasons (20). Before the operation, 20 of the 33
      patients (60.6%) presented urologic complications related to bladder management,
      including triggered micturition, indwelling catheter or intermittent
      catheterization: urethrocutaneous fistula (4), complicated enterocystoplasty (2),
      watering pot perineum and severe decubitus ulcerations (14). Ileal conduit (also
      named ileoureterostomy) was performed alone for 19 patients (57.6%), and in
      combination with simultaneous cystectomy in 14 patients. We reviewed patient
      outcome and early and late complications. RESULTS: Mean follow-up was 48 months
      (1 to 20 years). All problems related to catheters or incontinence had resolved.
      There were no deaths or early re-operations. Twelve patients (12 out of 33, 36%)
      had one or more peri-operative complication, including ileus (1), uretero-ileal
      anastomosis leak (1) and sepsis (1). During follow-up, four of the 19 patients
      who did not undergo cystectomy developed pyocystitis (3 secondary cystectomies
      performed between 6 and 56 months). All patients achieved perineal dryness.
      CONCLUSIONS: The ileal conduit procedure is a safe and well-tolerated procedure
      in neurologically impaired patients. This procedure is suitable for most
      neurogenic patients with refractory lower urinary tract dysfunctions.

PMID- 12185606
TI  - Protective effects of oral creatine supplementation on spinal cord injury in
      rats.
AB  - STUDY DESIGN: To evaluate a potential protective effect of increased creatine
      levels in spinal cord injury (SCI) in an animal model. OBJECTIVES: Acute SCI
      initiates a series of cellular and molecular events in the injured tissue leading
      to further damage in the surrounding area. This secondary damage is partly due to
      ischemia and a fatal intracellular loss of energy. Phospho-creatine in
      conjunction with the creatine kinase isoenzyme system acts as a potent
      intracellular energy buffer. Oral creatine supplementation has been shown to
      elevate the phospho-creatine content in brain and muscle tissue, leading to
      neuroprotective effects and increased muscle performance. SETTING: Zurich,
      Switzerland. METHODS: Twenty adult rats were fed for 4 weeks with or without
      creatine supplemented nutrition before undergoing a moderate spinal cord
      contusion. RESULTS: Following an initial complete hindlimb paralysis, rats of
      both groups substantially recovered within 1 week. However, creatine fed animals
      scored 2.8 points better than the controls in the BBB open field locomotor score
      (11.9 and 9.1 points respectively after 1 week; P=0.035, and 13 points compared
      to 11.4 after 2 weeks). The histological examination 2 weeks after SCI revealed
      that in all rats a cavity had developed which was comparable in size between the
      groups. In creatine fed rats, however, a significantly smaller amount of scar
      tissue surrounding the cavity was found. CONCLUSIONS: Thus creatine treatment
      seems to reduce the spread of secondary injury. Our results favour a pretreatment
      of patients with creatine for neuroprotection in cases of elective intramedullary
      spinal surgery. Further studies are needed to evaluate the benefit of immediate
      creatine administration in case of acute spinal cord or brain injury.

PMID- 12185607
TI  - The Tetrafigap Survey on the long-term outcome of tetraplegic spinal cord injured
      persons: Part III. Medical complications and associated factors.
AB  - STUDY DESIGN: To study the short- and long-term medical complications encountered
      in tetraplegic spinal cord injured persons (TSCI) and to give prominence to both
      the medical and socio-economic factors with which they are respectively
      associated. METHODS: The Tetrafigap Study is a multicentre epidemiological survey
      carried out using self-administered questionnaires studying the global long-term
      outcome of TSCI patients after the initial phase of rehabilitation. RESULTS: The
      data for 1668 patients were analyzed. The rate of rehospitalizations was 74.4%
      with on average three stays per patient and as reported causes, in descending
      order: urinary complications, systematic follow-up, pressure sores, respiratory
      complications, contractures, bowel complications, pains and secondary fractures
      of the lower limbs. At the time of the survey, 84.7% of patients mentioned
      awkward contractures, 73.8% pains, 55.9% embarrassing urinary leakage and 14.1%
      pressure sores. With regard to persons suffering from complete motor lesion,
      urinary complications and pressure sores were more frequently reported, whereas
      for persons suffering from incomplete motor lesions, awkward contractures and
      pains were more frequent. In the elderly, pains were more often mentioned, and
      pressure sores and pain were also the most common in patients coming from lower
      socio-professional status. Contractures and pain decreased with time. All these
      complications but pressure sores and pain are statistically interrelated.
      CONCLUSION: The medical complications of spinal cord injured persons are
      frequent, they are linked to biological, psychological and environmental factors,
      and are interrelated. Therefore, seeking mid- and long-term risk factors must be
      given priority in order to better adapt attempts at increasing secondary
      prevention.

PMID- 12185608
TI  - A PET study on the characterization of partially reversible radiogenic lower
      motor neurone disease.
AB  - OBJECTIVE: To investigate the pathomechanism of the rare radiogenic lower motor
      neurone disease (LMND) on the basis of a case history involving a partial
      functional recovery. PATIENT: A 31-year-old seminoma patient received
      postoperative para-aortic and para-iliac telecobalt irradiation with a
      biologically effective dose of 88 Gy(2) (44 Gy in 2 Gy fractions/day, with an
      estimated alpha/beta of 2 Gy) delivered to the spinal cord following a single
      cycle of chemotherapy. LMND developed 4 months after the completion of
      radiotherapy. The patient exhibited flaccid paraparesis of the lower extremities
      (without sensory or vegetative signs), followed by a worsening after further
      chemotherapy, due to pulmonary metastatization. A gradual spontaneous functional
      improvement commenced and led several years later to a stabilized state involving
      moderately severe symptoms. METHODS: In the 15th year of the clinical course,
      magnetic resonance imaging (MRI) and positron emission tomography (PET) with
      [(18)F]fluorodeoxyglucose (FDG) and [(11)C] methionine were conducted. Four lines
      of experiments (clonogenic assay using fibroblasts isolated from a skin biopsy
      sample of the patient, comet assay, micronucleus assay, and the testing of
      chromosome aberrations after in vitro irradiation of peripheral blood samples)
      were performed in a search for an increased individual radiosensitivity. RESULTS:
      MRI investigations failed to reveal any pathological change. PET demonstrated an
      increased FDG accumulation, but a negligible [(11)C] methionine uptake in the
      irradiated spinal cord segments. The radiobiological investigations did not
      indicate any sign of an increased individual radiosensitivity. CONCLUSIONS: We
      suggest that the observed partial functional recovery and stabilization of the
      symptoms of radiogenic LMND may be explained by the higher than normal density of
      sodium channels expressed along the demyelinated axons of the restored
      conduction. The increased energy demands of this type of conduction are proved by
      a higher metabolic rate (increased FDG uptake) of the irradiated spinal cord
      segments without a substantial regenerative process (lack of detectable protein
      synthesis).

PMID- 12185609
TI  - Thermoregulatory responses to exercise and warm water immersion in physically
      trained men with tetraplegia.
AB  - OBJECTIVE: To compare thermoregulatory responses of highly trained men who are
      tetraplegic during 40 min exercise at 65% [Vdot]O(2) peak and 60 min immersion in
      39 degrees C water. METHODS: Four physically trained men who are tetraplegic
      participated in three laboratory visits. The first visit involved familiarisation
      and then determination of [Vdot]O(2) peak using open circuit spirometry during an
      incremental test to exhaustion with each man propelling his sport wheelchair on a
      motor driven treadmill. The order of second and third visits was randomly
      allocated. Visit 2 involved 40 min of exercise at 65% [Vdot]O(2) peak propelling
      each man's sport wheelchair on treadmill. Visit 3 involved sitting immersed to
      nipple line in 39 degrees C water for 60 min. Venous blood was obtained pre,
      during and after each intervention and analyzed for haemoglobin, haematocrit and
      changes in plasma volume were calculated. Separated plasma was analyzed for
      noradrenalin and adrenalin (high performance liquid chromatography). Heart rate,
      rectal temperature, and sweat rate estimated from a sweat capsule placed on
      forehead (dew point hygrometry) were recorded throughout. RESULTS: [Vdot]O(2)
      peak and HR max of these subjects were 1.14+/-0.16 l.min(-1) and 99+/-4 b.min(-1)
      respectively. Heart rate preimmersion was 67+/-4 b.min(-1) rising to 75+/-4
      b.min(-1) after 40 min and 87+/-3 b.min(-1) after 60 min immersion. Heart rate
      was 68+/-3 b.min(-1) pre-exercise rising to 91+/-5 b.min(-1) after 40 min
      exercise. Rectal temperature rose from 35.97+/-0.30 degrees C pre immersion to
      37.32+/-0.51 degrees C after 60 min immersion, and from 36.42+/-0.20 degrees C
      pre-exercise to 36.67+/-0.19 degrees C after 40 min exercise. Haemoconcentration
      occurred during 40 min of exercise and haemodilution occurred throughout 60 min
      of water immersion. Three participants demonstrated no sweating on the forehead
      during immersion or exercise. One subject commenced sweating after 20 min
      exercise and after 5 min of immersion. CONCLUSION: Compared to exercise,
      immersion was associated with a lower heart rate, a lower plasma noradrenalin
      concentration and an expanded plasma volume. When considering exercise or warm
      water immersion as therapeutic modalities in men who are tetraplegic, attention
      should be paid to heat gain and changes in plasma volume.

PMID- 12185610
TI  - Charcot joint of the spine, a cause of autonomic dysreflexia in spinal cord
      injured patients.
AB  - STUDY DESIGN: Case report of two subjects. OBJECTIVE: Charcot joints of the spine
      as a cause of Autonomic Dysreflexia in spinal cord lesions. SETTING: Stoke
      Mandeville Hospital, UK. METHOD: Two patients with long standing spinal cord
      lesions developed symptoms of headaches and sweating associated with sitting up
      and transfers. In both cases no other cause was found to account for Autonomic
      Dysreflexia. RESULT: Charcot Joints of the spine below the level of injury were
      demonstrated in both cases and symptoms resolved with prolonged bed rest.
      CONCLUSION: As care of spinally injured patients continues to improve, they live
      longer and lead a more active lifestyle, it is expected that the incidence and
      prevalence of Charcot's joints will increase. Therefore the knowledge and
      heightened awareness of this entity, early diagnosis and detection with plain X
      rays for urinary surveillance, may reduce the morbidity in spinal cord injured
      patients.

PMID- 12185611
TI  - Cervical amyotrophy caused by hypertrophy of the posterior longitudinal ligament.
AB  - STUDY DESIGN: A case report. OBJECTIVES: To report a case of cervical amyotrophy
      caused by hypertrophy of the posterior longitudinal ligament (HPLL). SETTING:
      Department of Neurological Surgery, Aichi Medical University, Aichi, Japan.
      METHODS: The patient had severe muscular atrophy in the deltoid and triceps with
      slight localized hypesthesia in the C5 area and severely unstable gait due to
      diminished vibration sense in the knees and ankles. Magnetic resonance imaging
      (MRI) showed expanded cord compression from C4 to C6 with intramedullary high
      signal intensity due to HPLL. Transverse image MRI was useful to identify the
      HPLL. RESULTS: Resection of HPLL was achieved by an anterior approach.
      Histological findings of the surgical specimens showed thickening of the
      ligamentous tissue with proliferation of chondrocytes. CONCLUSIONS: HPLL should
      be included as a causative pathology of cervical spondylotic amyotrophy. Careful
      neurological examination including sensory examination of the lower limbs should
      be performed to avoid confusion with motor neuron disease.

PMID- 12185612
TI  - Prevention of pressure sore caused by indwelling urinary catheters.

PMID- 12185614
TI  - [Evidence-based medicine: a task for everybody].

PMID- 12185615
TI  - [Las falsas expectativas en cirugia oftalmologica].

PMID- 12185616
TI  - [About the adjustable sutures in ophthalmic plastic surgery].

PMID- 12185617
TI  - [Automated perimetry and neuro-ophthalmology. Topographic correlation].
AB  - Visual fields continue to be a key exploration for the diagnosis and follow-up of
      patients in neuro-ophthalmology. The pattern of visual field defects helps, and
      in many cases allows, the identification of brain damage location. Manual kinetic
      perimetry has been replaced by automated methods. 24-2 SITA (Humphrey Visual
      Field Analyser) and TOP (Octopus) are regarded as the standard perimetric
      explorations in neuro-ophthalmology. Goldmann perimetry remains as an useful
      exploration for temporal crescent detection in occipital lobe diseases, and it
      could be more accurate and consistent for studying lesions in the post-geniculate
      pathway. Frequency doubling perimetry could be useful for detecting neuro
      ophthalmic visual field defects, but does not provide an accurate
      characterisation of the lesions. From the neuro-ophthalmic point of view, visual
      field defects could be divided in pre-chiasmatics, chiasmatics and post
      chiasmatics. Pre-chiasmatic defects are strictly unilateral, do not respect the
      vertical meridian, often have a nasal step associated and are usually accompanied
      by ocular pathology detectable in an ophthalmic examination. The characteristic
      perimetric pattern of chiasmal disease is bi-temporal hemianopsia. Homonymous
      contralateral defects are the characteristic perimetric pattern of post-chiasmal
      disease, and their congruency increases when the lesions are closer to the
      occipital lobe. Neuroimage studies are mandatory in all patients with a
      perimetric defect pattern compatible with chiasmal or post-chiasmal lesions.
      Magnetic Resonance Imaging may be normal in a patient with homonymous defects in
      Alzheimer's disease, the Heidenhain variant of Creutzfeldt-Jakobs disease, carbon
      monoxide poisoning and mild occipital ischemia demonstrated by SPECT or PET
      imaging (Arch Soc Esp Oftalmol 2002; 77: 413-428).

PMID- 12185618
TI  - [Management of encapsulated blebs after glaucoma drainage device surgery].
AB  - PURPOSE: We analyse the different options for the management of encapsulated
      blebs after glaucoma drainage device surgery, specially subconjunctival 5
      fluouracil (5-FU) injections with or without associated needling. METHODS:
      Retrospective review of 20 eyes with encapsulated blebs following glaucoma
      drainage device surgery. All of the eyes received topical corticosteroids
      associated to digital massage. Subconjunctival 5-FU was necessary in 10 eyes,
      associated to needling of the bleb in 5 of them and to capsule excision in 2.
      RESULTS: Fifteen eyes were considered successes (complete in 10 eyes and
      uncomplete in 5). Eight of them had been treated with 5-FU (80% success in the 5
      FU treated eyes group), associated to needling and/or capsule excision in 4 of
      them. The remaining 7 eyes were only treated conservatively (70% success with
      corticoid therapy and digital pressure). CONCLUSIONS: We have obtained in our
      study very good results using subconjunctival 5-FU injections, associated in
      complicated or refractory cases to needling revision, in eyes with encapsulated
      blebs after glaucoma drainage device surgery, with no major complications (Arch
      Soc Esp Oftalmol 2002; 77: 429-434).

PMID- 12185619
TI  - [Retinal nerve fiber layer thickness in glaucomatous eyes. A comparative study
      between OCT and visual field].
AB  - PURPOSE: To investigate the retinal nerve fiber layer (RNFL) thickness in
      glaucomatous eyes using Optical Coherence Tomography (OCT). To compare the RNFL
      thickness with visual field damage (Humphrey field analyzer). MATERIAL AND
      METHODS: The mean RNFL thickness in glaucomatous eyes (n = 80) was compared with
      age-matched normal eyes (n = 40). Three circular scans were obtained for each eye
      using OCT (3.4 mm diameter). In each eye, average RNFL, 4 quadrants and 12
      meridians were calculated and compared. The superior-inferior asymmetry of RNFL
      was studied. The average RNFL thickness was compared with mean deviation (MD) and
      mean standard deviation (MSD) of SITA 24-2 visual field program. RESULTS: Mean
      RNFL was significantly thinner in glaucomatous eyes than in normal eyes
      (p<0.001). The RNFL thickness was decrease in the 4 quadrants and 11 of 12
      meridians studied in glaucomatous eyes (p<0.05). The superior-inferior asymmetry
      showed a significant difference in RNFL thickness at 30 degrees central meridian
      (p<0.05). Mean RNFL thickness was significantly associated with DM and DSM of
      visual field (p<0.001) in glaucomatous eyes. CONCLUSIONS: OCT revealed
      significant quantitative differences in RNFL thickness between glaucomatous and
      normal eyes. OCT showed a considerable measurements overlap between glaucomatous
      and normal eyes, which can limit the sensitivity and specificity of this
      instrument (Arch Soc Esp Oftalmol 2002; 77: 435-442).

PMID- 12185620
TI  - [No X-chromosome linked juvenile foveal retinoschisis].
AB  - PURPOSE: To describe the clinical characteristics of two cases of juvenile foveal
      retinoschisis in women with an atypical hereditary pattern, no X-chromosome
      linked. An autosomal recessive inheritance is proposed. METHODS: Two generations
      of a family (5 members) in which only two sisters were evaluated. The complete
      examination of these two cases includes retinography, fluorescein angiography,
      automated perimetry, color vision testing, electroretinogram, electrooculogram
      and visually evoked potentials. RESULTS: Comparing our cases with the classic
      form of X-linked juvenile retinoschisis, they are less severely affected. The
      best visual acuity and the less disturbed or even normal electroretinogram
      confirm this fact. We emphasise the existence of isolated plaques of retinal
      pigment epithelium atrophy with perivascular pigment clumps without foveal
      schisis in one patient, which could represent an evolved form of this entity.
      CONCLUSIONS: The hereditary foveal juvenile retinoschisis in women suggests an
      autosomal inheritance (autosomal recessive in our cases) and presents less severe
      involvement (Arch Soc Esp Oftalmol 2002; 77: 443-448).

PMID- 12185621
TI  - [A case of papilledema and Arnold-Chiari type I malformation].
AB  - CLINICAL CASE: A 12-year old girl was brought to the emergency ward because of
      headache and diplopia for 4 days. Bilateral papilledema was observed. Ancillary
      studies showed Arnold-Chiari Type I malformation without hydrocephalia. Cranial
      decompression treatment was performed but papilledema persisted and a progressive
      visual field deterioration was assessed. One month later, an optic nerve sheath
      fenestration was performed. DISCUSSION: Arnold-Chiari I malformation is
      characterized by downward displacement of cerebellar tonsils below the foramen
      magnum plane. It usually remains asymptomatic or appears in adulthood with
      brainstem compression-related symptoms. Surgical decompression of the posterior
      cranial fossa is mandatory in symptomatic cases. In our case, intracranial
      hypertension persisted because of postoperative subdural hygromas. Visual field
      deterioration was resolved by optic nerve sheath fenestration (Arch Soc Esp
      Oftalmol 2002; 77: 449-454).

PMID- 12185622
TI  - [Polypoidal choroidal vasculopathy in a patient with a melanocytoma of the optic
      nerve].
AB  - PURPOSE/METHOD: The choroidal neovascularization (CNV) may be associated with
      several types of choroidal tumors. The polypoidal choroidal vasculopathy (PVC) is
      a variant of the choroidal neovascularization. We present a case of PCV
      associated with melanocytoma of the optic nerve. RESULTS/CONCLUSIONS: Although we
      cannot rule out that these two entities are independent of each other, the
      reported cases of choroidal tumors with CNV, the publication of a similar case
      and the epidemiological similarity between melanocytoma and PCV leads us to think
      that they may be related. We confirm the efficacy of laser argon treatment (Arch
      Soc Esp Oftalmol 2002; 77: 455-458).

PMID- 12185623
TI  - [Suprachoroidal haemorrhage and acute glaucoma associated with systemic
      fibrinolysis].
AB  - PURPOSE/METHOD: To describe the clinical case of a patient with acute myocardial
      infarction and an ocular haemorrhage as a complication of the use of systemic
      thrombolytic agents. RESULTS/CONCLUSIONS: A patient who received therapy with
      tissue plasminogen activator for an acute myocardial infarction developed three
      hours later a massive suprachoroidal haemorrhage with secondary acute angle
      closure. In patients who have undergone systemic thrombolytic agents, the
      presence of loss of vision and pain must alert to the possibility of secondary
      ocular haemorrhage. These patients may benefit from continuous control (Arch Soc
      Esp Oftalmol 2002; 77: 459-462).

PMID- 12185624
TI  - [Historical background of studies on eye morphogenesis (I)].

PMID- 12185626
TI  - Chronic disease management programmes are criticised by doctors.

PMID- 12185625
TI  - [Jose Rizal y Mercado. Calambria (Luzon), 1861-Manila, 1896].

PMID- 12185627
TI  - Failure to inform public is undermining confidence in clinical trials.

PMID- 12185628
TI  - [Cost control and quality of care].

PMID- 12185629
TI  - [Scientific production: criteria of impact evaluation].

PMID- 12185630
TI  - [Supraperiosteal treatment of infraorbital fat body (SOOF) in inferior
      blepharoplasty].

PMID- 12185631
TI  - [Airway obstruction after central venous catheterization].

PMID- 12185632
TI  - [Functions of the splenic remnant after subtotal splenectomy for treatment of
      severe splenic injuries].
AB  - PURPOSE: To evaluate clinical and laboratory variables in patients submitted to
      subtotal splenectomy. METHODS: 34 patients with severe trauma of the spleen and
      its pedicle were studied: 25 patients were submitted to subtotal splenectomy,
      preserving only the upper pole of the spleen (Group I), 9 were submitted to total
      splenectomy (Group II), and other 22 people with intact spleen were the control
      (Group III). Immediate and late postoperative complications were investigated.
      Laboratory exams were performed in the late postoperative period (red blood
      cells, hemoglobin, white blood cells, platelets and Howell-Jolly bodies). We
      studied the B- and T-lymphocyte counts and the immunoglobulins A, G and M (IgA,
      IgG and IgM) levels. Splenic scintigraphy with technetium 99mTc sulfur colloid
      was carried out on all patients. RESULTS: Group II presented Howell-Jolly bodies
      increased and low level of immunoglobulin M. The splenic scintigraphy
      demonstrated the viability and the filtering function of the splenic remnant in
      Group I. CONCLUSIONS: Subtotal splenectomy is a surgical alternative technique
      for treatment of severe distal injuries of the spleen or when its main vessels
      are damaged.

PMID- 12185633
TI  - [Histopathological and immunohistochemical analysis (proliferating cel nuclear
      antigen) of patients with invasive cervical carcinoma before and after
      radiotherapy and surgery].
AB  - OBJECTIVE: To search for residual disease and to analyse the Proliferating
      Cellular Nuclear Antigen (PCNA) status, in patients with cervical squamous cell
      carcinoma, treated with both radiotherapy and surgery. METHODS: Histological
      slides from 16 patients with uterine cervix cancer, treated between April 1986
      and August 1998, with preoperative radiotherapy and surgery, were reviewed. PCNA
      immunohistochemical reactivity of these samples was evaluated, using the IMAGELAB
      2.3 computer image analysis system. RESULTS: Residual carcinoma were found in
      eight cases (50%) and no malignant features was found in eight cases (50%). The
      mean value of PCNA before radiotherapy in patients with residual cancer was
      61.56% and in cases without residual cancer was 60%. Its expression before
      radiotherapy was between 27.91% and 89.93% (60% average), while after
      radiotherapy it varied between 55.80% and 86.73% (74% average). CONCLUSIONS: The
      association between preoperative radiotherapy followed by surgery is adequate to
      treat patients with cervical cancer, when radical treatment is not possible.
      Meanwhile, exclusive radiotherapy shows a significant failure rate, detected
      after surgery and PCNA analysis.

PMID- 12185634
TI  - [Skin diseases in patients with AIDS: study in 55 cases in Uberlandia, MG,
      Brazil].
AB  - Fifty-five patients with acquired immunodeficiency syndrome (AIDS) seen at the
      Dermatology outpatient clinic and who had mucocutaneous diseases were studied.
      These diseases, some of them opportunistic, are common but difficult to diagnose
      given the atypical features of the lesions. OBJECTIVES: The aim of this study was
      to analyse the frequency and clinical presentation of dermatoses related to Aids
      seen at the Dermatology outpatient clinic. METHODS: Fifty-five patients with Aids
      and mucocutaneous lesions were examined from 1995 to 1997 in a cross-sectional
      study carried out at the Dermatology outpatient clinic of the Universidade
      Federal de Uberlandia (Minas Gerais, Brazil). Biopsies and cultures were
      undertaken for laboratory diagnosis. RESULTS: One hundred sixteen dermatoses were
      diagnosed. Fungal infections (78%) were the commonest among them, followed by
      viral infections (40%), papulosquamous disorders (27%), papular eruptions (18%),
      adverse drug reactions (10%), tumors (9%) and a variety of others (7%). The
      majority of the patients (67%) had more than one type of skin disorder.
      CONCLUSIONS: In agreement with previous literature data fungal and viral
      infections were confirmed as the most frequent skin disorders in HIV-positive
      patients. Dermatological examination, laboratory tests and skin biopsy for
      histopathological study are necessary for appropriate diagnostic investigation of
      HIV-related mucocutaneous diseases considering that atypical presentation occurs
      in a large proportion of the patients.

PMID- 12185635
TI  - [Prevalence of hepatitis C in patients with systemic lupus erythematosus in the
      Hospital of Federal University of Rio de Janeiro (HUCCF)].
AB  - BACKGROUND: Patients with systemic lupus erythematosus (SLE) are at risk for the
      acquisition of hepatitis C, owing to frequent hospitalization and
      hemotransfusion. Many clinical and laboratory manifestations related to auto
      immunity are shared between Lupus and HCV infected patients. OBJECTIVE: To
      determine the prevalence of hepatitis C in the population with SLE monitored in
      the out-patient service of the special programs in--Collagenoses--of the
      University Hospital Clementino Fraga Filho (HUCFF-UFRJ). METHODS: A Cross
      sectional study was performed, including 91 patients with the diagnosis of
      probable or definitive SLE (with 3 or more of the 11 diagnostic criteria for SLE
      used by the American College of Rheumatology-ACR) proceeding from the mentioned
      center between April/97 to September/97. Patients were evaluated on clinical and
      laboratory basis to determine activity of lupus disease (SLEDAI). All of patients
      were tested with UBI HCVEIA 4.0 assay and INNO-LIAHCV AbIII confirmatory assay.
      PCR was performed on all EIA positive INNO-LIAHCV AbIII assay positive patients
      besides 32 patients negatives in both serological assays. RESULTS: A
      significative increase in HCV prevalence among SLE patients was observed when
      compared with a control group of blood donors at HUCFF-UFRJ (6.6 and 1.39%,
      respectively; p = 0.02 and confidence interval of 95% = 5.5-13.8). However, if
      confirmative assays (INNO-LIA HCV ABIII and PCR) are used, this difference can
      not be observed any more HCV prevalence of 2.2% with confidence interval of 95% =
      0.2-7.7). CONCLUSIONS: HCV prevalence using ELISA assay for screening showed a
      significant difference between SLE patients and a blood donors control group (6.6
      and 1.39% respectively). However, if confirmatory assays are subsequently
      applied, no difference in HCV prevalence among both groups can be observed.
      Patients with a possible diagnosis of SLE should have a cost/benefit analysis of
      testing for HCV.

PMID- 12185637
TI  - [Prevalence of respiratory symptoms and clinical conditions and associated asthma
      in schoolchildren in Rio de Janeiro, Brazil].
AB  - OBJECTIVE: We compared the prevalence of respiratory symptoms and clinical
      conditions associated to bronchial asthma and exercise-induced bronchospasm (EIB)
      in schoolchildren from public and private schools. METHODS: We conducted a cross
      sectional questionnaire (ATS-DLD-78 C modified) survey in 2941 children 6-14
      years of age attending public (n = 1951) and private (n = 1350) elementary and
      secondary schools in Rio de Janeiro. RESULTS: Wheezing was found in 842 (28.6%)
      students; 684 students (23.3%) showed symptoms of EIB; 342 (11.6%) children
      related hospitalization owing to respiratory problems; previous use of
      bronchodilators (BD) was reported by 1072 (36.5%) children; bronchiolitis,
      pneumonia and rhinitis were observed in respectively 40 (1.4%), 185 (6.3%) and
      1088 (37%) children. Family history of atopy and immunotherapy were related by
      1794 (61%) and 577 (19.6%) students, respectively. Asthma diagnosed by a
      physician was observed in 779 (26.5%) children. Using questionnaire criteria we
      found 638 (21.7%) children with asthma; 354 in public and 284 in private schools.
      Data statistical analysis showed a higher frequency of EIB, hospitalization and
      pneumonia in students attending public schools (26.3%, 15.9% and 7.2%,
      respectively). Children in private schools showed a higher frequency of family
      history of atopy and immunotherapy (63.7% and 23.6%, respectively). CONCLUSIONS:
      We found a high prevalence of asthma among students of public and private
      elementary and secondary schools in Rio de Janeiro, without statistical
      differences between the two groups of children. Episodes of EIB were also highly
      prevalent in this study, with a higher frequency among students of public
      schools.

PMID- 12185636
TI  - [Vitamin A: blood level and dietetics intake in stunted children and adolescents
      without hormonal disease].
AB  - OBJECTIVES: To determine the vitamin A intake and the blood levels of carotenoids
      and retinol in stunted children and adolescents without hormonal disease,
      assisted in the Clinic of Pediatric Endocrinology of the Center for Nutrition and
      Child Development--Department of Health, State of Sao Paulo, Brazil. METHODS: We
      evaluated, in a prospective and randomized trial, 47 prepubertal patients between
      4 and 14 years old. All patients were submitted to anthropometric evaluation,
      bone age, bioelectric impedance and serum retional and carotenoid levels.
      RESULTS: The average of the stature z score was -2.4; 20% of the patients were
      undernourished, 25.5% they had inadequacy of the fat mass as well as larger delay
      of the bone age. The more stunted the patients the lower were the carotenoid
      levels. There was no relationship between the levels of retinol and carotenoids
      and the growth velocity. In 82.9% of the recall record of food intake, the
      vitamin A intake was lower than 50% of the established one in the Food Guide
      Pyramid. CONCLUSION: There is a high prevalence of malnutrition, bone age delay
      and inadequacy of the levels of carotenoids and vitamin A intake in stunted
      children and adolescents.

PMID- 12185638
TI  - [Preliminary study about the utility of gastric tonometry during the weaning from
      mechanical ventilation].
AB  - OBJECTIVE: The intramucosal pHi measurement has been studied and evaluated as a
      minimally invasive method able to offer information about the tissue oxygenation.
      It's most important advantage is to be a regional not systemic measurement in a
      place with early changes of blood flow, even in the compensated states of shock,
      as the gastrointestinal tract. The weaning from mechanical ventilation may cause
      cardiac output changes as well as redistribution of blood flow to the respiratory
      muscles. Our aim was to test the hypothesis that the splanchnic blood flow
      decreases may occur after patients extubation, detected by pHi reduction, and to
      verify if pHi can be a good predictive index for weaning from mechanical
      ventilation. METHODS: Clinical prospective non-randomized, uncontrolled study,
      realized in a University Hospital PICU. Assessment of pHi (gastric) in 15
      children in the post-operative of elective cardiac surgery with cardiopulmonary
      bypass. A tonometer with saline solution was used and measurements were made one
      hour before and after extubation. The patients were divided into two groups with
      pHi < or = or > 7.32. The Wilcoxon test was used for statistical analysis.
      RESULTS: The pHi decreased after extubation in 10 patients (66.7%). The overall
      mean before extubation was 7.32 +/- 0.10 and after extubation was 7.27 +/- 0.10
      (p = 0.096). In the group with pHi < or = 7.32 and > 7.32 the means were 7.25 +/-
      0.05 to 7.32 +/- 0.10 (p = 0.72) and 7.41 +/- 0.07 to 7.31 +/- 0.10 (p = 0.059),
      before and after extubation respectively. None of the patients presented
      complications due to the procedure; no deaths or development of multiple organ
      failure occurred. All of the patients were successfully weaned. CONCLUSIONS: Our
      results show pHi decreasing confirming splanchnic blood flow reduction after
      extubation, however in despite of this circulatory change the patients were
      weaned from mechanical ventilation and successfully extubated. In this trial the
      pHi was not a good predictive index. The pHi monitoring seems to be useful and
      reliable, but it requires further studies to evaluate its sensitivity.

PMID- 12185639
TI  - [Hpv cofactors in cervical carcinogenesis].
AB  - Human papillomavirus (HPV) plays a central rule in uterine cervix carcinogenesis.
      Other factors direct or indirectly influence the installation of this mechanism
      in cervical squamous epithelium. Investigations regarding mechanisms of
      interaction of these factors with viral elements are found in the literature of
      the last 20 years. The present review article discusses possible co-factors of
      HPV in the genesis of the squamous carcinoma of uterine cervix, taking into
      account only the factors whose association with the virus or cervical cancer has
      been documented by experimental studies, and not based just on clinical or
      epidemiological data. Among the approached parameters are immunological factors
      (local and humoral immune response), the association with Acquired Immune
      Deficiency Syndrome, genetic factors as protein p53 polymorphism, tabagism and
      the use of oral contraceptives. All these factors interact in variable intensity
      with oncoproteins and other HPV elements, increasing and facilitating the virus
      action in host cells, leading to the development of immortalization and
      carcinogenesis.

PMID- 12185641
TI  - [Diagnosis and treatment for carcinoid tumors in the digestive tract].
AB  - The authors analyzed the characteristics of carcinoid tumors according to their
      site in the digestive tract. Despite their low speed of growing and metastasis
      process, such neoplasias are malignant and must be submitted to surgical
      resection. Advanced cases with metastases are treated with somatostatin
      derivatives, lessening symptoms, causing occasional regression of lesions and
      presenting an extended survival. Appendicular and rectal lesions have a better
      prognosis maybe due to the early diagnosis performed.

PMID- 12185640
TI  - [Trauma in the elderly].
AB  - The populational growth of the elderly, associated to a healthier and more active
      life, make this group of people more exposed to accidents. In some countries,
      trauma in the elderly is responsible for a high mortality rate,
      disproportionately higher than in the adults. This fact consumes a great portion
      of health care resources and implies in a high social cost. The distinct
      physiologic characteristics of the elderly and the frequent presence of
      associated diseases make that these patients behave differently and in a more
      complex way than patients of other ages. These particularities make that health
      care to the elderly victims of trauma have to be different. The present revision
      is about aspects of epidemiology, prevention, physiology, health care and
      rehabilitation of the elderly victims of trauma.

PMID- 12185642
TI  - Spasm of the near reflex associated with head injury.
AB  - Spasm of the near reflex is characterized by intermittent miosis, convergence
      spasm and pseudomyopia with blurred vision at distance. Usually, it is a
      functional disorder in young patients with underlying emotional problems. Only
      rarely is it caused by organic disorder. We report a patient who developed
      convergent spasm associated with miosis after head trauma at the age of 84 years.

PMID- 12185643
TI  - Non-concordance in amblyopia treatment: the effective use of 'smileys'.
AB  - PURPOSE: The success of any specific occlusion regimen is limited by the level of
      concordance, which is difficult to measure accurately in patching treatment. The
      aim of this study was to investigate prospectively the concordance rate of a
      group of children with strabismic and/or anisometropic amblyopia using a
      schematic diary based on completing 'smiley' images, filled in by the child under
      parental supervision, and to assess the effect of correlates such as initial
      visual acuity, age, and total and daily occlusion time on concordance. METHODS:
      We recruited 51 amblyopic children aged 13 months to 12 years (mean 6.57 +/-
      2.82). The median duration of treatment was 16 weeks. Non-concordance was defined
      as occluding less than 75% of the prescribed time and was analyzed using a
      concordance index calculated from occlusion time recorded in the diary/prescribed
      occlusion time. RESULTS: Of the 51 patients followed prospectively, 12 (23.5%)
      failed to return their diaries (Group 1); 27 (52.9%) complied with occlusion
      (Group 2); and 12 (23.5%) failed to comply with occlusion completely (Group 3).
      The total proportion of non-concordance was 47.1% (Group 1 + Group 3).
      Concordance was not significantly related to initial visual acuity (r = -0.22, p
      = 0.19), patient age (F = 1.0787, p = 0.349) or total occlusion time (X2 = 2.779,
      p = 0.249), but the number of daily occlusion hours showed significant difference
      in Group 1 (X2 = 15.894, p = 0.000). When the three groups were compared for
      change in visual acuity, a significant difference was found between group 1 and
      group 2 (X2 = 6.125, p = 0.047). CONCLUSION: The substantial proportion of non
      concordance in our study suggests that, although useful for recording purposes,
      parental diaries may not be stimulating enough to increase the overall level of
      concordance. Therefore, other forms of monitoring need to be explored.

PMID- 12185644
TI  - A case of paradoxical diplopia in large-angle consecutive exotropia.
AB  - PURPOSE: To describe the investigation and subsequent management of paradoxical
      diplopia in unsightly exotropia. A 32-year-old lady requested surgical correction
      of a large manifest consecutive exotropia which, on initial correction with any
      base-in prism, was accompanied by paradoxical diplopia. METHODS: Botulinum toxin
      to the right lateral rectus reduced the deviation to 30 delta over a one-week
      period. The residual deviation was corrected with base-in Fresnel prisms which
      the patient wore constantly for another two weeks. Although there was
      demonstrable diplopia initially, it disappeared after 3-4 days of prism wear.
      Surgery was carried out comprising right lateral rectus recession (6 mm) and
      right medial rectus advancement from 12 mm to 6 mm posterior to the limbus.
      RESULTS: There was no diplopia following the surgery and the residual
      exodeviation measured 6 delta for near and 16 delta for distance (fixing OD). The
      patient remains symptom-free and cosmetically excellent. CONCLUSION: A gradual
      progressive reduction in the deviation using a combination of Botulinum toxin and
      prisms allowed a more informative conclusion to be made regarding the potential
      post-operative sensory status in this patient, by allowing her to slowly adjust
      to an altered ocular alignment. In patients with non-functional strabismus who
      may be at risk from post-operative diplopia, a trial with prisms over a few weeks
      with or without the addition of Botulinum toxin is advocated.

PMID- 12185645
TI  - A case of congenital oblique retraction syndrome with upshoot in adduction.
AB  - We treated a 27-year-old man who suffered from a congenital eye movement
      abnormality. The patient could not adduct the left eye, and showed exotropia,
      hypertropia and excyclotropia of the left eye. The range of abduction was also
      limited. The left eye showed marked upshoot on right gaze and eye globe
      retraction on right down gaze under conditions of right-eye viewing. The superior
      rectus muscle of the left eye was recessed and transposed nasally. The insertion
      of the superior oblique muscle was found to be defective. The upshoot and face
      turn improved after surgery. The globe retraction on right down gaze was no
      longer evident. We believe that the superior rectus muscle was innervated by an
      anomalous branch of the oculomotor nerve, which was originally destined to
      innervate the medial rectus, and that simultaneous contraction of the superior
      and inferior rectus muscles caused the globe retraction on right down gaze. This
      case also suggests the possibility that some part of the upshoot in adduction in
      Duane's syndrome is due to the co-contraction of the superior and medial rectus
      muscles due to this innervation anomaly.

PMID- 12185646
TI  - On the mechanics of the ocular muscles. Part I. 1869.

PMID- 12185647
TI  - Eye movement training and recording in alert macaque monkeys: 1. Operant visual
      conditioning; 2. Magnetic search coil and head restraint surgical implantation;
      3. Calibration and recording.
AB  - PURPOSE: To describe current methodology used to: a) train alert adult macaque
      monkeys to perform visual fixation tasks, b) implant binocular magnetic scleral
      search coils and attach a head restraint, and c) precisely record their fixation
      and pursuit eye movements. METHODS: Animals are trained to sit in a primate chair
      and manipulate a lever. The animal turns on a laser spot (< 1 degree of arc) by
      pulling the lever. The spot dims after a variable, randomized period of time
      (luminance decrement 30-80%) and if the monkey releases the lever within 150-500
      msec of dimming, a small bolus of juice is squirted via a servo into the monkey's
      mouth as a reward. The small size of the spot, the difficulty of detecting the
      dimming, and the short reaction time required for reward act in concert to assure
      attentive foveal fixation. After training, a search coil is implanted
      subconjunctivally in each eye and a polycarbonate head restraint device is
      attached to the skull. With the animal at the center of magnetic field coils, eye
      position is then calibrated precisely by requiring the animal to perform the
      dimming task at known positions of gaze. Fixation, vergence and pursuit eye
      movements are recorded by rewarding the animal for positioning the fovea of the
      eye within a small fixation 'window' encompassing the position of a stationary or
      moving target. A cover test of binocular eye alignment is performed by having the
      animal view through liquid crystal shutters that can be switched instantaneously
      from transparent to opaque. These methods have been used to train and to record
      eye movements in over 20 monkeys, and a representative sample of our experience
      in eight animals is reported in the Results. RESULTS: Normal monkeys, and monkeys
      who had strabismus or amblyopia, required an average of 53 days to learn to
      fixate steadily for a minimum of 5 sec with a dimming-detection performance of at
      least 75% correct. Implanted coils provided good signals for durations ranging
      from 4 months to longer than 3 years (average greater than 1 year) before signs
      of breakage or extrusion. Head restraints under daily use have lasted an average
      of 11 months (range 5 months to greater than 2 years) before spontaneous
      detachment. CONCLUSION: The training and surgical techniques described provide an
      efficient, straightforward method for recording precise binocular eye movements
      in awake monkeys.

PMID- 12185648
TI  - [Clinicopathological and immunohistochemical characteristics of stromal sarcoma
      of the duodenum].

PMID- 12185649
TI  - [Non-surgical conservative treatment of thoracic esophageal perforations].

PMID- 12185650
TI  - [Renal cell carcinoma and ulcerative colitis].

PMID- 12185651
TI  - [Primary hepatic abscess caused by Actinomyces meyeri].

PMID- 12185652
TI  - [Colorectal trauma caused by foreign bodies].

PMID- 12185654
TI  - Lung changes and cytokine levels in a model of experimental acute pancreatitis.
AB  - AIM: Prognosis of acute pancreatitis is related mainly to systemic involvement.
      The establishment of this systemic inflammation is mediated by proinflammatory
      cytokines. Our aim is to study serum levels of some proinflammatory cytokines and
      the associated damage of the lung in a model of experimental acute pancreatitis.
      EXPERIMENTAL DESIGN: Eighty seven male Wistar rats were divided into two groups:
      group A (control) with saline solution administration; group B with acute
      pancreatitis induced by intraperitoneal caerulein (50 mg/kg every hour, 4 doses).
      The animals were killed at 0, 2, 6 and 24 hours of the last dose of caerulein or
      saline solution. Pancreatic and pulmonary histology were examined, and serum
      levels of IL-1 beta, TNF-alpha and IL-6 were evaluated, as well as some
      laboratory parameters as indicators of systemic involvement. RESULTS: The
      administration of caerulein induced an acute edematous pancreatitis without
      mortality and with a trend towards resolution in 24 hours. IL-1 beta in animals
      with acute pancreatitis showed significantly higher levels than in the control
      group at 6 hours. Serum transaminases, urea and creatinine were also
      significantly higher at 2 and 6 h. The group with acute pancreatitis showed
      histological lung damage all over the study. CONCLUSIONS: In our model of acute
      pancreatitis we observed systemic involvement as judged by alterations of serum
      transaminases and parameters of renal function, as well as histological lung
      damage, that correlated with an increase in serum levels of IL-1b.

PMID- 12185653
TI  - Cytokine pulmonary involvement in an experimental pancreatitis model.

PMID- 12185655
TI  - Prospective analysis of marlex mesh repair for symptomatic rectocele with
      obstructive defecation.
AB  - OBJECTIVE: Evaluation of perineoplasty with marlex mesh in symptomatic rectocele
      with obstructive defecation and evaluation of the incidence of postobstetric
      perineal tear in patients with symptomatic rectocele. DESIGN: Prospective
      analysis of 11 consecutive patients undergoing elective rectocele repair.
      Prospective analysis of sphicnter postobstetric tears in patients with rectocele.
      RESULTS: Incidence of postobstetric perineal tears in 100 per cent of patients.
      Absence of obstructive defecation symptoms in 100 per cent of patients. Mesh
      displacement in 5/8 cases. CONCLUSIONS: Endoanal ultrasound secreening in
      patients with symptomatic rectocele is mandatory. Prosthetic repair eliminates
      obstructive defecation symptoms in 100 per cent of patients. Mesh is well
      tolerated although it has to be fixed in the suprasphincteric area and with non
      reabsorbable stitches.

PMID- 12185656
TI  - Relationship between degree of cellular differentiation in colorectal cancer and
      topographical distribution.
AB  - OBJECTIVES: To demonstrate the relationship between degree of cellular
      differentiation in colorectal cancer and topographical distribution in 215
      patients diagnosed with colorectal cancer from 1997 to 2000. MATERIAL AND
      METHODS: 215 patients (129 men and 86 women) were studied prospectively with a
      mean age of 64 years (range: 23-84 years). In all patients we performed a full
      colonoscopy with several biopsies (in patients with colon stenosis we used barium
      enema), radiographic studies (CT, abdominal ultrasounds), and laboratory tests
      for serum tumour markers (CEA, Ca 19-9, alpha-fetoprotein). The topographic
      location of colorectal cancer was: rectum 35%, sigmoid colon 31%, descending
      colon 10%, transverse colon 6%, ascending colon 9%, caecum 5%, and we included
      anorectal cancer 4%. RESULTS: According to histological differentiation we found:
      A) well-differentiated tumours 101/215 (47%); B) moderately-differentiated
      tumours 98/215 (45.5%), and C) poorly-differentiated tumours 16/215 (7.5%). We
      found no significant association among histological differentiation, topographic
      location, stage according to the Astler-Coller classification, sex or age (p =
      ns). The prevalence of well-differentiated tumours in men was 49% and 43% in
      women; of moderately-differentiated cancers in men was 43%, and 49% in women; for
      poorly-differentiated tumours in men was 7.5%, and 7.2% in women. Regarding
      tumour location, 165 cancers were found in the left colon: 80 were well
      differentiated, 77 moderately differentiated and 8 poorly differentiated. In the
      transverse colon we found 12 tumours: 7 well differentiated, 3 moderately
      differentiated and 2 poorly differentiated. 30 cancers were localized in the
      right colon: 11 well differentiated, 15 moderately differentiated and 4 poorly
      differentiated. In the anorectum 8 tumours were found: 3 well differentiated, 3
      moderately differentiated and 2 poorly differentiated. According to staging
      classification, well differentiated tumours (101/215) were more common in Dukes'
      C2 (20.7%) and B1 (32.6%), moderately differentiated cancers (98/215) were in B1
      (28.5%) and C2 (20.4%), and poorly differentiated tumours (16) were more common
      in Dukes' C2 (25%), without differences among other stages (p = ns). CONCLUSIONS:
      According to our results we have found that histological differentiation of
      colorectal cancer has no association with topographic location, and it is
      independent of sex or age. We have not found any relationship either between
      histological differentiation and stage in the Astler-Coller classification, but
      well differentiated cancers were more common at any location, age or sex.

PMID- 12185657
TI  - PPI test and endoscopy in GERD.

PMID- 12185658
TI  - Biliary cystadenoma with elevated CA 19.9.
AB  - We report a case of a large biliary cystadenoma occupying the entire peritoneal
      cavity, manifesting as an abdominal swelling for years and an elevation of CA
      19.9 serum levels. Serum CA 19.9 levels fell to normal values after surgical
      excision. Recognition and management of this rare hepatic lesion is discussed.

PMID- 12185659
TI  - He's a lover, not a fighter--smell, sex and civility.

PMID- 12185660
TI  - Estrogen receptor-beta and the cardiovascular system.

PMID- 12185661
TI  - beta-cell biology in the 21st century.

PMID- 12185662
TI  - Overfeeding the islets.

PMID- 12185663
TI  - Depression eased for Parkinson males.

PMID- 12185664
TI  - The role of vitamin D in mild to moderate chronic kidney disease.
AB  - Dietary vitamin D is a prohormone that is metabolized to the bioactive vitamin D
      hormone, 1 alpha, 25-dihydroxyvitamin D [1,25-(OH)2D]. 1,25-(OH)2D has been
      implicated in a variety of regulatory pathways that extend well beyond its
      traditional function in Ca2+ homeostasis. In uncovering these diverse functions,
      investigators have focused on the complex interaction between 1,25-(OH)2D and
      parathyroid hormone (PTH). Here, we present an overview of the functions of
      vitamin D hormone and PTH in the clinical context of secondary
      hyperparathyroidism. We discuss recent developments in treatment that address
      imbalances in vitamin D hormone and PTH levels, supporting the argument that
      early intervention can reduce the risk of metabolic complications caused by
      vitamin D hormone deficiency in patients with chronic kidney disease.

PMID- 12185665
TI  - Elucidation of estrogen receptor function in bone with the use of mouse models.
AB  - Since the discovery that estrogen receptors (ERs) are present in bone cells,
      there has been intense research into the action of estrogen in bone. During the
      past decade, humans with disturbed estrogen signaling, either as a result of ER
      alpha or aromatase deficiency, have been reported. Furthermore, mouse models have
      been established with a deficiency of ER alpha, ER beta or both, in addition to
      deficiency of aromatase. This review focuses on data accumulated during the past
      three years from studies of knockout mice with impaired estrogen signaling
      resulting from ER or aromatase deficiency.

PMID- 12185666
TI  - Recent insights into organogenesis of the adrenal cortex.
AB  - The primary endocrine organs responsible for steroid hormone biosynthesis--the
      adrenal cortex and gonads--are derived from the urogenital ridge. Several recent
      discoveries in human and mouse genetics have begun to unravel the complex genetic
      cascade that dictates adrenocortical cell lineage, proliferation and
      differentiation. The factors that regulate adrenocortical organogenesis and the
      maintenance of growth promote or block a cascade of transcription factors that
      differentially coordinate the proliferation and differentiation of the gland.
      Here, we outline the developmental milestones of the adrenal cortex with recent
      contributions to the field, focusing on factors that have been shown to play a
      role in vivo in humans and mice.

PMID- 12185667
TI  - Islet abnormalities in the pathogenesis of autoimmune diabetes.
AB  - Type 1 diabetes mellitus is a T-cell-mediated autoimmune disease that results in
      the destruction of the insulin-producing beta cells in the pancreatic islets of
      Langerhans. In spite of extensive genetic and immunological studies, mainly
      performed in the non-obese diabetic (NOD) spontaneous mouse model, the etiology
      of the autoimmune attack remains unknown. Several autoantigens have been
      identified and numerous studies have suggested a role for defective regulation of
      immune function. However, this account does not explain why the autoimmune
      process specifically affects the insulin-producing beta cells. Thus, abnormal
      immune regulation might explain the predisposition to autoimmunity in general,
      but additional factors should then determine the target of the autoimmune attack.
      Here, we review the evidence that abnormalities in islet cell differentiation and
      function exist that might trigger the immune system towards beta-cell
      autoimmunity in humans and NOD mice.

PMID- 12185668
TI  - Thyroid hormone transporters: recent advances.
AB  - Thyroid hormones, being hydrophobic, were thought to enter target cell membranes
      by passive diffusion. However, recent studies have documented the existence of
      numerous organic anion transport systems, about half of which also transport
      thyroid hormones into (and possibly out of) a variety of target cells. Several of
      the genes encoding thyroid hormone transporters have been characterized by means
      of molecular approaches. Here, we discuss the classification of thyroid hormone
      transporters, with emphasis on how they are influenced by their ionic milieu and
      what their symported organic anions are.

PMID- 12185669
TI  - To ERR in the estrogen pathway.
AB  - Estrogens control a variety of physiological and disease-linked processes, most
      notably reproduction, bone remodeling and breast cancer, and their effects are
      transduced through classic unclear receptors referred to as estrogen receptor
      alpha (ER alpha) and ER beta. Recent results obtained using the estrogen-related
      receptors (ERR alpha, -beta and -gamma), a subfamily of orphan nuclear receptors
      closely related to the ERs, have shown that the ERRs share target genes,
      coregulatory proteins, ligands and sites of action with the ERs. In addition, the
      ERRs can actively influence the estrogenic response, suggesting that
      pharmacological modulation of ERR activity will be clinically useful to prevent
      and/or treat a variety of conditions related to women's health.

PMID- 12185670
TI  - When density fails to predict bone strength.

PMID- 12185672
TI  - Asymmetric photoreactions as the origin of biomolecular homochirality: a critical
      review.
AB  - The role of asymmetric photoreactions (occurring in space or on the primitive
      Earth) in the origin of biomolecular homochirality is critically reviewed. A
      general description of the various possible ways for light to interact with
      chiral molecules is first presented on the basis of a series expansion of the
      dielectric constant: natural, magnetic and magnetochiral circular dichroism are
      identified with the first three terms in this development. Natural and
      magnetochiral circular dichroism may cause, through asymmetric photolysis, an
      enantiomeric excess in a racemic mixture of chiral molecules irradiated,
      respectively, by circularly polarized ultraviolet light, or by unpolarized
      ultraviolet light in the presence of a magnetic field non-perpendicular to the
      light beam. Terrestrial and extraterrestrial sites matching these conditions are
      then critically reviewed. Finally, we stress the possibility to arrive at the
      homochirality of amino acids through a path involving D-ribose during RNA world
      as an alternative to the usual scenarios operating directly on amino acids.

PMID- 12185671
TI  - D-amino acids in living higher organisms.
AB  - The homochirality of biological amino acids (L-amino acids) and of the RNA/DNA
      backbone (D-ribose) might have become established before the origin of life. It
      has been considered that D-amino acids and L-sugars were eliminated on the
      primitive Earth. Therefore, the presence and function of D-amino acids in living
      organisms have not been studied except for D-amino acids in the cell walls of
      microorganisms. However, D-amino acids were recently found in various living
      higher organisms in the form of free amino acids, peptides, and proteins. Free D
      aspartate and D-serine are present and may have important physiological functions
      in mammals. D-amino acids in peptides are well known as opioid peptides and
      neuropeptides. In protein, D-aspartate residues increase during aging. This
      review deals with recent advances in the study of D-amino acids in higher
      organisms.

PMID- 12185673
TI  - Relative amino acid concentrations as a signature for parent body processes of
      carbonaceous chondrites.
AB  - Most meteorites are thought to have originated from objects in the asteroid belt.
      Carbonaceous chondrites, which contain significant amounts of organic carbon
      including complex organic compounds, have also been suggested to be derived from
      comets. The current model for the synthesis of organic compounds found in
      carbonaceous chondrites includes the survival of interstellar organic compounds
      and the processing of some of these compounds on the meteoritic parent body. The
      amino acid composition of five CM carbonaceous chondrites, two CIs, one CR, and
      one CV3 have been measured using hot water extraction-vapor hydrolysis, OPA/NAC
      derivatization and high-performance liquid chromatography (HPLC). Total amino
      acid abundances in the bulk meteorites as well as the amino acid concentrations
      relative to glycine = 1.0 for beta-alanine, alpha-aminoisobutyric acid and D
      alanine were determined. Additional data for three Antarctic CM meteorites were
      obtained from the literature. All CM meteorites analyzed in this study show a
      complex distribution of amino acids and a high variability in total concentration
      ranging from approximately 15,300 to approximately 5800 parts per billion (ppb),
      while the CIs show a total amino acid abundance of approximately 4300 ppb. The
      relatively (compared to glycine) high AIB content found in all the CMs is a
      strong indicator that Strecker-cyanohydrin synthesis is the dominant pathway for
      the formation of amino acids found in these meteorites. The data from the
      Antarctic CM carbonaceous chondrites are inconsistent with the results from the
      other CMs, perhaps due to influences from the Antarctic ice that were effective
      during their residence time. In contrast to CMs, the data from the CI
      carbonaceous chondrites indicate that the Strecker synthesis was not active on
      their parent bodies.

PMID- 12185674
TI  - Dipeptides and diketopiperazines in the Yamato-791198 and Murchison carbonaceous
      chondrites.
AB  - The Yamato-791198 and Murchison carbonaceous chondrites were analyzed for
      dipeptides and diketopiperazines as well as amino acids and hydantoins by gas
      chromatography combined with mass spectrometry. Glycylglycine (gly-gly) and
      cyclo(gly-gly) were detected at the concentrations of 11 and 18 pmol g-1,
      respectively, in Yamato-791198, and 4 and 23 pmol g-1, respectively, in
      Murchison. No other dipeptide and diketopiperazine were detected. Five hydantoins
      were detected at 8 to 65 pmol g-1 in Yamato-791198 and seven in Murchison at 6 to
      104 pmol g-1. Total concentration of the glycine (gly) dimers is approximately
      four orders of magnitude less than the concentration of free gly in Yamato
      791198, and three orders of magnitude less than that in Murchison. The absence of
      L- and LL-stereoisomers of dipeptides consisting of protein amino acids indicates
      that gly-gly and cyclo(gly-gly) detected are native to the chondries and not from
      terrestrial contaminants. A possibility was discussed that the gly dimers might
      have been formed by condensation of gly monomers but not formed through N
      carboxyanhydrides of gly.

PMID- 12185675
TI  - Circular polarization of light by planet Mercury and enantiomorphism of its
      surface minerals.
AB  - Different mechanisms for the generation of circular polarization by the surface
      of planets and satellites are described. The observed values for Venus, the Moon,
      Mars, and Jupiter obtained by photo-polarimetric measurements with Earth based
      telescopes, showed accordance with theory. However, for planet Mercury asymmetric
      parameters in the circular polarization were measured that do not fit with
      calculations. For BepiColombo, the ESA cornerstone mission 5 to Mercury, we
      propose to investigate this phenomenon using a concept which includes two
      instruments. The first instrument is a high-resolution optical polarimeter,
      capable to determine and map the circular polarization by remote scanning of
      Mercury's surface from the Mercury Planetary Orbiter MPO. The second instrument
      is an in situ sensor for the detection of the enantiomorphism of surface crystals
      and minerals, proposed to be included in the Mercury Lander MSE.

PMID- 12185676
TI  - Kaoru Harada, for the love of amino acids.

PMID- 12185677
TI  - A new pathway to aspartic acid from urea and maleic acid affected by ultraviolet
      light.
AB  - The photochemistry of a mixture of urea and maleic acid, which are thought to
      have been widely present on the primitive Earth, was studied in order to examine
      a possibility of the formation of amino acids. When an aqueous solution of urea
      and maleic acid was irradiated with an ultraviolet light of wavelength 172 nm,
      urea was revealed to be rather resistant to photochemical decomposition. In
      contrast, maleic acid was completely decomposed within 4 h, reflecting the
      reactivity of a C-C double bond in the molecule. In the reaction mixture, 2
      isoureidosuccinic acid was detected. The acid was considered to be formed by
      addition of an isoureido radical which had been produced from urea by the action
      of a hydroxyl radical, to a C-C double bond of maleic acid. The isoureido group
      of the product was revealed to undergo thermal rearrangement to afford 2
      ureidosuccinic acid (N-carbamoylaspartic acid). The result suggested a novel
      pathway leading to the formation of aspartic acid from non-amino acid precursors,
      possibly effected by UV-light on the primitive Earth. The formation of
      ureidocarboxylic acids is of another significance, since they are capable of
      undergoing thermal polymerization, resulting in formation of polyamino acids.

PMID- 12185678
TI  - Synthesis of adenine from HCN tetramer and ammonium formate.
AB  - Adenine is formed in about 18% yield when HCN tetramer is heated with ammonium
      formate at 110 degrees C. The prebiotic significance of this reaction is
      discussed.

PMID- 12185679
TI  - [Characteristics of defective strains of methicillin resistance Staphylococcus
      aureus that do not produce coagulase or CF].
AB  - The aim of the study was to estimate frequency of coagulase-negative and CF
      negative strains among methicillin-resistant Staphylococcus aureus (MRSA) and to
      assess their homogeneicity in respect of genotype, phagotype and drug resistance
      pattern. A total of 186 MRSA strains collected from different hospitals in Gdansk
      region were studied. Gens: nuc, mecA, and coa were identified by PCR method. The
      coagulase tube test for staphylocoagulase and the slide test for clumping factor
      were used. Coagulase-negative and CF-negative MRSA strains were confirmed by PCR
      RFLP method of coa gene; phage typing and drug resistance pattern were evaluated
      by disc diffusion test. The results of the study showed low frequency of both
      coagulase-negative and CF-negative MRSA strains (7.25% and 3.76% respectively).
      Among MRSA population tested the simultaneous occurrence of the strains lacking
      coagulase and clumping factor was not observed. All coagulase negative MRSA had
      coagulase gene (coa) and differed from CF-negative strains in respect of coa
      gene.

PMID- 12185680
TI  - [Conjugative transfer of glycopeptide and macrolide resistant genes among
      Enterococci and from Enterococcus faecalis to Staphylococcus aureus].
AB  - The resistance determinants were transferred from clinical strains of enterococci
      to Staphylococcus aureus strains. As recipients methicillin-resistant and
      methicillin-susceptible strains were used and the filter-mating procedure was
      performed. The transconjugants resistant to erythromycin were obtained in the
      case of all recipients, in one case the vanA determinant conferring the
      resistance to vancomycin was transferred together with erythromycin resistance.
      However the resistance was very unstable and the level was not as high as in the
      case of Enterococcus faecalis donor strain. The vanA determinant was easily
      transferred between enterococcal strains by the conjugation and a transfer
      occurred of vanA alone or together with erythromycin resistance.

PMID- 12185681
TI  - [Occurrence of bacteria in the mouth from genera of Micrococcus, Kocuria,
      Nesterenkonia, Kytococcus and Dermacoccus].
AB  - The aim of the study was to assess the prevalence of different bacteria in the
      oral cavity. The bacteria were present in the oral cavities of 73 (48.7%) of 150
      individuals. Nesterenkonia halobia, the most frequently isolated species, was
      found in 20 (27%) individuals, Micrococcus luteus in 16 (22%), Kocuria kristinae
      in 12 (16%), Kocuria varians in 10 (14%), Dermacoccus sedentarius in 9 (12%),
      Micrococcus lylae in 8 (11%), and Kytococcus nishinomiyaensis in 3 (4%). Mean
      counts of these microorganisms were relatively low and amounted in log10 CFU/ml
      saliva for M. luteus 1.87 +/- 0.52, for M. lylae 2.03 +/- 0.39, for N. halobia
      2.14 +/- 0.56, for K. kristinae 2.20 +/- 0.69, for K. varians 2.19 +/- 0.67, for
      K. nishinomiyaensis 1.72 +/- 0.39, and for D. sedentarius 2.27 +/- 0.55. The
      factor limiting the population sizes of these microorganisms was most probably
      the antagonistic activity of the bacteria living in oral cavity.

PMID- 12185682
TI  - [Novelty of laboratory diagnosis for diphtheria].
AB  - Selected elements of simplified, bacteriological diagnosis of diphtheria were
      presented. The procedure of Corynebacterium strains isolation from diphtheria
      suspected persons and performing of toxin testing of potentially toxigenic
      isolates: C. diphtheriae, C. ulcerans and C. pseudotuberculosis were shortened.
      The role of selective tellurite media was underlined but Loeffler medium was
      rejected. Columbia blood agar plate was utilized for preliminary culture.
      Biochemical tests and toxin testing were performed from this medium. Presented
      diphtheria diagnosis scheme may have practical application for the laboratory
      work in Poland.

PMID- 12185683
TI  - [Clostridium difficile strains not producing Toxin A, but producing Toxin B
      [toxA(-)tox B(+)]--etiologic agent of antibiotic associated diarrhoea (AAD) in
      Poland].
AB  - Previously, toxin A-negative/toxin B-positive Clostridium difficile strains were
      not thought to be associated with clinically significant diseases. In our study
      among 159 tested C. difficile strains isolated from feacal samples from 413
      patients with antibiotic associated diarrhoea (AAD) 17 strains (11%) were
      negative in the "Culturette Brand Toxin" CD (Becton-Dickinson) for detection
      toxin A and positive in the TOX A/B test, designed for detection of both toxins.
      The conserved regions of both toxin genes were detectable in all of isolates
      studied by the PCR. Nine of these C. difficile strains had a deletion in the A
      gene and remaining 8 strains, revealed an amplicon with the expected size of
      approximately 2500 bp. In this paper we described the first time the toxin A
      negative/toxin B-positive C. difficile strains with deletion in toxin A gene,
      isolated from the faecal samples of patient with AAD in Poland.

PMID- 12185684
TI  - [Enterotoxic strains of Clostridium perfringens and sporulation].
AB  - Clostridium perfringens strains of A type capable of enterotoxin (CPE) synthesis
      may be a potential source of food-poisoning. Suitability of methods for CPE
      detection on the protein level is limited by difficulties in inducing sporulation
      in vitro. A number of unknown facts concerning coregulation the sporulation
      processes and CPE synthesis are recognised. The goal of the work was to determine
      the level of correlation between CPE synthesis and spores formation. Enterotoxin
      and cpe gen were detected by RPLA after sporulation induction test and by methods
      based on amplification on the DNA and mRNA levels. Sixty-four C. perfringens
      strains of A type isolated from patients with food poisoning symptoms and from
      food samples were analysed. Collection of isolates was differentiated as not
      enterotoxic, enterotoxic, and potentially enterotoxic strains based on
      appropriate strain profile: plc(+), cpe(-), CPE(-); plc(+), cpe(+), CPE(+); and
      plc(+), cpe(-), CPE(-), respectively. No significant difference between
      expression of cpe mRNA in vegetative and sporulation phase was found. The
      obtained results indicate that sporulation is not an essential factor for cpe
      gene expression.

PMID- 12185685
TI  - [The effect of culture conditions on hydrophobic properties of Pseudomonas
      aeruginosa].
AB  - The cell surface hydrophobicity (CSH) plays an important role in a adhesion of
      bacteria on solid surfaces. CSH of 62 Pseudomonas aeruginosa strains isolated
      from humans and different animals was assessed using the ammonium sulfate salt
      aggregation test. Bacteria were grown for 24 h and 48 h at a room temperature (22
      degrees C) and 37 degrees C on enrichment broth and agar (Biomed) and tryptic soy
      agar (Difco). The hydrophobic properties of the Pseudomonas aeruginosa strains
      were depended on the temperature, time of the culture of bacteria and the kind of
      media. CSH properties were most frequently expressed when the analyzed strains
      were cultured in enrichment broth. In a such conditions Pseudomonas aeruginosa
      strains were more hydrophobic when grown at 22 degrees C (94% after 24 h and 87%
      after 48%) than those at 37 degrees C (72% after 24 h and 71% after 48 h). Among
      strains cultured in tryptic soy agar at 37 degrees C, 48% after 24 h and 75%
      after 48 h were autoaggregating, representing very strong hydrophobic properties.

PMID- 12185686
TI  - [Evaluation of commercial usefulness for microparticle agglutination Serodia-Myco
      II test for serodiagnosis of Mycoplasma pneumonia infections].
AB  - The usefulness of Serodia-Myco II agglutination test (Fujirebio, Japan) for
      diagnosis of the M. pneumoniae infections was evaluated. A total of 66 serum
      samples obtained from patients with respiratory tract infections were tested by
      Serodia-Myco II test, complement fixation (CF) test, ELISA-IgG/-IgM, and by latex
      agglutination (LA) test prepared in our laboratory. Using CF test and ELISA as
      the reference tests, Serodia-Myco II test gave too many false positive results.
      This test in relation to CF test, ELISA-IgM, ELISA-IgG, and LA test showed a very
      high sensitivity, virtually 100%, with a low specificity, below 50%. It seems
      that oversensitivity of the Serodia-Myco II test is caused by too low cut off
      (40) value recommended by the manufacturer. The Serodia-Myco II test may be used
      in routine serodiagnosis of mycoplasmosis under condition that cut off value will
      be raised to 160 and the positive results of this test will be confirmed by the
      CF test or ELISA.

PMID- 12185687
TI  - [Microbiologic analysis of results from blood cultures].
AB  - The aim of our investigations was the microbiological analysis together with the
      evaluation of sensitivity of bacteria frequently isolated from blood cultures.
      Blood samples were taken from patients with symptoms suggesting bacteremia in
      Rydygier's Hospital in Cracow. A total of 11,170 blood samples taken from 1997 to
      2000 were tested. Automatic VITAL system (bioMerieux) was applied to culture and
      detect microorganisms. Bacteria were identified by ATB system (bioMerieux).
      Susceptibility was detected by ATB and disc diffusion method. Percentage of
      positive results relating to detection of microorganisms of clinical significance
      was 16.9% (1891 cultures). Staphylococcus spp. (Staph. epidermidis in range 22.8%
      to 21.9%), Enterococcus spp. and Streptococcus spp. were most frequently isolated
      species among aerobic Gram-positive bacteria. In 2000, compared to 1997 the
      number of isolates of MRSA increased considerably (from 1.8% to 6.8%). In blood
      infections the increase of frequency of E. coli bacteria was also noted: 6.1% and
      11.4% in 1997 and 2000, respectively. Among non-fermentant bacilli the percentage
      of occurrence of P. aeruginosa in the period of 4 years was comparable in the
      range 7.3% in 1997 to 7.2% in 2000. The increase in the frequency of blood
      infections of A. baumanii was also noticed (respectively from 4.8% to 9.9%).
      Susceptibility of P. aeruginosa strains to selected beta-lactame antibiotics and
      aminoglycosydes increased in 2000 in comparison to 1999. A. baumanii strains were
      100% sensitive only to imipenem.

PMID- 12185688
TI  - [Polymerase chain reaction in diagnosis of toxoplasmosis of the central nervous
      system: effect of methods for isolating DNA from samples of cerebrospinal fluid
      on results of the reaction].
AB  - We examined influence of the method of isolation of DNA from cerebrospinal fluid
      samples on results of PCR in the diagnosis of toxoplasmosis of the central
      nervous system. Three different protocols of DNA isolation were used for DNA
      extraction from 360 samples made of cerebrospinal fluid spiked with tachyzoites
      of Toxoplasma gondii: thermic, enzymatic and enzymatic-filtering. Purified DNA
      samples were tested by PCR with primers T15 and T16 designed for the B1 gene of
      the parasite. Enzymatic method of DNA isolation appeared most effective allowing
      detection of T. gondii DNA in 50% of samples containing single parasite cell.

PMID- 12185689
TI  - [VISA and hetero-VISA among Staphylococcus aureus strains isolated from clinical
      cases].
AB  - The VISA (vancomycin intermediate Staphylococcus aureus) and hetero-VISA strains
      were found among all isolates of S. aureus obtained in the years 1997-2000. The
      frequency of VISA was 0.3% and h-VISA was about 3%. Most but not all of the h
      VISA and all VISA strains were methicillin resistant. Moreover the usefulness of
      different methods enabling recognition of the h-VISA strains was compared.

PMID- 12185690
TI  - [The effect of culture conditions on expression of surface proteins from
      coagulase-negative staphylococci isolated from clinical material of newborns
      hospitalized in an intensive care unit].
AB  - A surface adhesion is a fundamental stage, in a pathogenesis of inflammations
      caused by coagulase-negative staphylococci, at which surface proteins take part.
      The proteins that were found at S. saprophyticus and ascribed to take part in
      polystiren plates adhesion: SSP-1 and SSP-2 could be an example. In this work the
      effort to esteem surface protein expression of various kinds of coagulase
      negative staphylococcus according to cultivation conditions has been made. The
      studies carried out with 31 staphylococcus strains being obtained from new-born
      children hospitalised in Neonatology Clinic helped to analyse the similarities
      among these proteins in the area of a given strain cultivated on different
      mediums. The examined strains belonged to five different species and it had been
      taken into consideration during the results esteem. On the grounds of
      electrophoretic surface proteins division the charts dysometric analysis was
      created showing interdependence between Rf for surface proteins and optical
      density. Afterwards an analysis for each strain was done taking into account a
      sort of medium on which the cultivation had been placed. S. haemolyticus strains
      analysis cultivated on three different mediums allows to isolate two protein
      groups showing similar expression of both low- and high-molecular proteins. For
      the majority of strains belonging to the same species one can observe a similar
      expression within low- and high-molecular surface proteins regardless of
      cultivation conditions. Recurrence of the electrophoretic pictures regardless of
      changes in cultivation conditions, creates the base for the recognised proteins
      identification and also for the proteins with unmarked activity isolation.

PMID- 12185691
TI  - [Ability of Staphylococcus cohnii strains to adhere to epithelial cells and solid
      surfaces in the hospital environment].
AB  - Presented study describes abilities of staphylococci to adhere to exfoliated
      cheek and uroepithelial epithelium cells and to various surfaces such as
      plastics, glass and steel. The subject of the study were strains of
      Staphylococcus cohnii ssp. cohnii and Staphylococcus cohnii ssp. urealyticus
      isolated from Intensive Care Unit of Pediatric Hospital. Staphylococcus cohnii
      ssp.cohnii adhered in great number to epithelial cells. However, the adhesion
      differed by individual strains. We did not find relationship between slime
      production and adherence to epithelial cell. Most of investigated strains adhered
      closely to surfaces--especially of plastics and glass. This phenomenon was
      stronger in the presence of culture medium and phosphate buffer.

PMID- 12185692
TI  - [Evaluation of practical usefulness of selected phenotypic and genotypic markers
      for pathogenicity of enterotoxic and entero-hemorrhagic strains of E.coli. ].
AB  - This study included a description of enterotoxic and verocytotoxic activity of
      thirty strains of E. coli and their ability to produce beta-haemolysis in a ram
      blood medium. Enterotoxic and verocytoxic activity was determined by using RPLA
      test. The synthesis of enterotoxin LT was observed in 10 strains and the
      production of E. coli shiga toxins type 1--Stx1 (1 strain) or type 2 (2 strains)
      was observed in 3 strains of serotype O157: H7. The beta-haemolytic
      characteristics in vitro were demonstrated by 17 strains (57%) isolated from
      pigs. Among them 16 (94%) were found to possess the genes that determine the
      enterotoxins or enterotoxins and E. coli shiga toxin Stx2v synthesis. Using the
      PCR technique, 21 strains (70%) were found to possess the genetic determinants of
      enterotoxins LT, STa and/or STb synthesis or enterotoxins and E. coli shiga toxin
      Stx2v synthesis. Further genetic study showed that the strains possessed the
      genes elt and estB were predominant (33%) among the toxic strains of E. coli
      isolated from piglets and calves.

PMID- 12185693
TI  - [Etiology of acute diarrheas in children from the Lodz region. I. Occurrence of
      etiologic agents].
AB  - The aim of this study was determination of the etiologic agents (bacterial,
      fungal or viral) of acute diarrheas in children from the Lodz region, suffering
      from acute diarrhoea during the period from October 1998 to February 2001.
      Rotaviruses were detected by the latex test. Other microorganisms belonging to
      the Enterobacteriaceae, Pseudomonadaceae and Vibrionaceae families, as well as
      the genera Listeria, Campylobacter, Candida, Staphylococcus were cultured on
      standard or selective culture media according to the NDH recommendations and
      identification by means of API system. Acute diarrhea in 155 small children below
      6 years of age from the Lodz region were caused by rotaviruses (n = 42; 27%).
      Enteropathogenic strains of Escherichia coli (n = 25; 16.1%) occupied the third
      place after Salmonella bacteria (n = 30; 19.3%--second place). Among bacterial
      etiologic factors of diarrhea Campylobacter bacteria showed high frequency of
      occurrence (n = 22; 14.1%). The investigations enabled identification both the
      mixed infections (n = 25; 16.1%) and more rare etiologic agents of diarrhea.
      CONCLUSIONS: 1. Acute diarrhea in children from the region Lodz were most
      frequently caused by rotaviruses; 2. Modern microbiological diagnostics of acute
      diarrhea in children should be multilateral, taking account of the mixed
      infections and expanding the routine search for bacteria of the genus
      Campylobacter.

PMID- 12185694
TI  - [Occurrence of beta-lactamase types ESBL and AmpC among gram-negative rods
      isolated from food].
AB  - The aim of the study was to isolate extended spectrum beta-laktamases (ESBL) and
      chromosomal beta-laktamases AmpC producing strains from food products. A total of
      739 Gram-negative bacteria were tested with double disc diffusion method using
      cefotaxim, ceftasidim and amoxycillin with clavulanic acid. One strain producing
      ESBL and belonging to Stenotrophomonas maltophilia was detected from the ice
      cream (0.14% of all strains). From different food products a total of 14
      microorganisms (1.9%) having AmpC enzymes have been isolated. They belonged to
      Enterobacter spp, Hafnia spp, Morganella spp, Citrobacter, Acinetobacter, and
      Cedecea. Appearance of strains producing beta-laktamases ESBL and AmpC among
      microorganism isolated from food make it necessary to monitor enzymes activity
      during routine microbiological control of foods.

PMID- 12185695
TI  - [Utilization of hybridization in situ and PCR in situ methods to detect latent
      infection by the wild strain of HSV-1 and by a mutant with reduced reactivation].
AB  - The aim of the study was to detect the number of latently infected cells with
      wild type virus and with mutant with reduced reactivation. Using PCR in situ
      method we established, that the number of cells containing genome of these
      viruses do not differ especially between them. The number of cells with LAT
      expression is significantly reduced in the ganglia infected with mutant with
      impaired reactivation as we showed using in situ hybridization. Based on the
      observations of other authors, that high expression of LATs takes place in cells
      with high copy number of viral DNA our results showed, that after infection of
      mice with mutant with reduced reactivation less cells contain high copy number of
      viral DNA than after infection with wild type KOS. We suggest that impaired
      reactivation of an ICP22 mutant occurs as a result of reduced number of cells
      with high copy number of viral DNA.

PMID- 12185697
TI  - [Use of molecular biology methods for diagnosing fungal infections].
AB  - A total of 130 various clinical materials taken from 48 children with suspected
      systemic fungal infection were used for the study. Clinical samples were tested
      by use of classical mycological procedures well as by use of molecular technique
      (PCR assay). The fragments of 125-bp (EO3) and 317 bp (HSP) specific for C.
      albicans were used for amplification. Fifty seven samples (48%) were positive for
      Candida albicans and eighty four (68%) by use of PCR. It should be stressed that
      4 blood samples, 21 urine samples and 5 other samples were positive by use of
      molecular technique, only. PCR is sensitive and rapid method for detection and
      identification of Candida albicans from clinical materials of children with
      fungal infection. This technique can be applied for monitoring presence of fungal
      DNA in tested samples during antifungal therapy.

PMID- 12185696
TI  - [Prevalence of TT virus in patients with hepatitis B,C and hepatitis of unknown
      etiology].
AB  - Discovery of TT virus in 1997 gave raise to intensive subsequent studies to learn
      about its structure, features and, what is the most important, about its role in
      pathogenesis of liver disease. The aim of the work was to analyze prevalence of
      TTV DNA in patients with diagnosed hepatitis B, C, that of unknown etiology and
      in healthy blood donors as well. Additionally the divergence of TTV sequence was
      estimated in selected cases. TTV DNA was detected by PCR technique using specific
      oligonucleotide primers for coding regions. TT virus has been detected in 25.6%
      (32/125) HBsAg positive patients and in 23.9% (51/213) HCV infected patients. In
      healthy blood donors the frequency of TTV was 24.3% (34/140) similarly to that
      found in HCV and HBV infected patients. The frequency of TTV DNA among patients
      with hepatitis of unknown etiology was 9.1%. This result was statistically
      significant lower than in the other groups. When detected sequences have been
      compared to these from NCBI base the homology result was 71% to 95%, and among
      different patients and groups of patients identity was 46% to 73%. On the basis
      of the obtained results it can be concluded that it is very unlikely that TTV
      coinfection plays any significant role in HCV or HBV infection. The hypothetical
      role of TTV infection in the etiopathogenesis of cryptogenic chronic hepatitis
      has not been confirmed. The results obtained in the small group of patients with
      hepatitis of unknown etiology are not conclusive and should be taken with some
      precaution. The final conclusion is the TTV coinfection does not contribute to
      the liver pathology. The divergence of TTV sequences may explain the various
      frequency of TTV viremia reported by other authors.

PMID- 12185698
TI  - [Yeast-like fungi as etiologic agents of blood infections in patients
      hospitalized in 1998-1999].
AB  - The aim of the study was the analysis of frequency of yeast-like fungi as
      etiological agents of fungemias in patients hospitalized in operative and
      conservative wards of Medical Academy Central Clinical Hospital in Warsaw in 1998
      1999. Peripheral blood samples and collected from vascular catheters were
      incubated in BacT/Alert system(Organon Teknika, USA). Positive blood samples were
      inoculated on Sabouraud medium with chloramphenicol (bioMerieux, France) (the
      time of cultivation from 48 h to 7 days at 30 C) and on chromogenic medium BBL
      CHROMagar Candida (Becton Dickinson, USA). Fungal strains were identified by
      standard mycological procedures using ID 32 C strips (ATB system, bioMerieux,
      France) and tests of Sanofi Diagnostics Pasteur (France). The total number of
      positive blood cultures was 1724. Fifty eight fungal strains were isolated from
      blood samples (3.36%). Strains belonged to 4 genera: Candida (55), Trichosporon
      (1), Saccharomyces (1) and Pichia (1). Thirty eight fungal strains were isolated
      from peripheral blood samples. Forty seven fungal strains were cultured from
      patients hospitalized in operative wards. Among fungi isolated from peripheral
      blood samples C. albicans (10), C. glabrata (9) and C. parapsilosis (5) strains
      dominated. From blood samples collected from vascular catheters most often C.
      albicans (7), C. glabrata (4) and C. parapsilosis (3) were isolated.

PMID- 12185699
TI  - [Antibiotic resistance of staphylococci isolated from outpatients].
AB  - The aim of the study was to determine susceptibility of 587 strains of S. aureus
      and 85 strains of coagulase-negative staphylococci isolated from outpatients in
      Poznan to co-trimoxazole, amoxycillin/clavulanic acid, erythromycin, gentamycin,
      doxycycline, ampicillin, oxacillin, cephradine, clindamycin and neomycin. Also
      methicillin-resistant strains were determined as well as strains ability to
      produce beta-lactamases. Susceptibility testing and examination of methicillin
      resistant strains were performed by the disc diffusion techniques according to
      recommendation of NCCLS. Methicillin-resistant strains were additionally examined
      to their sensitivity to vankomycin and teicoplanin. beta-lactamase production was
      detected using nitrocefin impregnated discs and iodometric method.
      Amoxacillin/clavulanic acid, gentamycin, co-trimoxazole, cephradin, oxacillin and
      clindamycin occurred to be very active against both, S. aureus and coagulase
      negative staphylococci. 84.7% to 100% of examined strains were sensitive to these
      drugs. Doxycyclin, erythromycin and ampicillin were less effective. Nine strains
      (1.5%) of 587 strains of S. aureus as well as 7 strains (8.7%) of coagulase
      negative staphylococci were methicillin-resistant. All of methicillin-resistant
      strains were sensitive to vancomycin and teicoplanin. More than 75% of S. aureus
      and close to 50% of coagulase-negative staphylococci were able to produce beta
      lactamases.

PMID- 12185700
TI  - [Gelatinolitic and proteolytic activity of Wharton's jelly in EPH-gestosis
      (preeclampsia)].
AB  - EPH-gestosis is accompanied by an extensive remodeling of the extracellular
      matrix of Wharton's jelly. The gelatinolytic and proteolytic activities were
      measured. A decrease in gelatinolityc activity and an increase in proteolytic
      activity in EPH-gestosis were observed. The decrease in gelatinase activity in
      EPH-gestosis may be one of factors involved in extracellular matrix rebuilding of
      Wharton's jelly.

PMID- 12185701
TI  - [Growth factors in pregnancy complications with preeclampsia].
AB  - The aim of the study was to determine the concentrations of TGF-beta, PDGF and
      VEGF growth factors in peripheral blood. The examinations were carried out in the
      group of pregnant women with preeclampsia. The results were compared to those
      obtained in a control group of healthy pregnant women. The statistically
      significant increase in all examined growth factors was observed in women with
      preeclampsia in comparison to healthy women. The results suggest that growth
      factors may play an important role in etiology and pathophysiology of
      preeclampsia.

PMID- 12185702
TI  - [Fetal arterial oxygen saturation (FSpO2) during the second stage of labor after
      training for childbirth].
AB  - OBJECTIVE AND DESIGN: The aim of the research was to determine the effects of
      participating in training program for childbirth in Maternity School in Lodz on
      the state of the fetus. In the above research, the authors presented the foetal
      oxygen saturation (FSpO2) during the second stage of labour among the women
      participating in Maternity School as well as a control group. Our study analysed
      the neonatal outcome too (umbilical arterial blood pH and 5 min. Apgar score).
      MATERIAL AND METHODS: The test group consisted of eighty seven (87) healthy
      primigravidas of whom forty two (42) participated in classes in the Maternity
      School and forty fifth (45) made up the control group. Validity of the
      correlation was assessed by means of t-Student's table of N--2 degree of freedom.
      RESULTS: The medium parameters of FSpO2 values and duration of the second stage
      of labor in both groups were shown. Statistically significant differences between
      the groups were found in duration the second stage of labour--in Maternity School
      group being shorter. Statistically significant differences in FSpO2 values
      between groups were not observed.

PMID- 12185703
TI  - [The effect of umbilical cord encirclement on fetal arterial oxygen saturation
      values].
AB  - AIM: Our purpose was to study fetal arterial oxygen saturation trends by
      continuous pulse oximetry during labour in subjects with and without umbilical
      cord encirclement. MATERIAL AND METHODS: The study was carried out in 46 pregnant
      women in the 38.9 +/- 1.4 weeks of pregnancy and the 15 of them with umbilical
      cord encirclement, established respectively after delivery. The fetus was
      monitored continuously with an Oxford S 8000 system and pulse oximeter Nellcor N
      400. The medium parameters of FSpO2 values during progressive stages of labour in
      both groups were shown. The importance of the correlation was assessed using the
      t-Student's table of N--2 degree of freedom. RESULTS: In those two groups no
      significant difference between FspO2 value in first stage of labour was found. In
      second stage of labour our study showed tendency for higher oxygen saturation
      values in foetuses without umbilical cord compression.

PMID- 12185704
TI  - [Delivery and puerperium of women after kinesitherapy--evaluation].
AB  - AIM: The attempt to estimate the influence of physical exercises for course of
      delivery and confinement. MATERIAL AND METHODS: The investigations were conducted
      at hospitals in following cities and towns: Bielsko--Biala, Nowy Targ, Sucha
      Beskidzka and in Gliwice. The efficiency of School of Birth program was studied.
      The 384 women with random chosen and the natural deliveries were examined. The
      interviews, analysis of hospitals cards and School of Birth specifications were
      studied. The estimations of efficiency of newborn children in Apgar scale and
      psychological and physical state of health of the women after delivers conducted
      by doctors were taken into consideration.

PMID- 12185705
TI  - [Detection of chromosomal aneuploidies in fetus by multiplex Q-PCR method].
AB  - With application of the quantitative PCR, Q-PCR, two cases of aneuploidy: trisomy
      18 and trisomy 21 were detected in the course of routine prenatal diagnosis in
      amniotic cells DNA obtained from 1.5 ml of the amniotic fluid. The conventional
      cytogenetic methods confirmed the diagnosis and the following karyotypes were
      established: 47,XY,+21 and 47,XX,+13. The presented results show that by means of
      the Q-PCR the aneuploidy diagnosis can be obtained within 48 hours.

PMID- 12185706
TI  - [Lead and cadmium concentration in human semen].
AB  - OBJECTIVES: The aim of our study was to specify influence of lead and cadmium on
      semen parameters. MATERIAL AND METHODS: Concentrations of both elements were
      determined in semen samples by atomic absorption spectrophotometry of 57 men with
      teratozoospermic, astenozoospermic and oligozoospermic (studied group) and 39
      normozoospermic group (control group). Semen morphology was conducted in
      accordance with WHO regulations. RESULTS AND CONCLUSIONS: We did not find any
      difference in concentration of these elements in both groups. We found a positive
      correlation between lead and cadmium in seminal plasma.

PMID- 12185707
TI  - [Carcinoma developing in extragonadal endometriosis--analysis of two cases].
AB  - Two cases of invasive carcinoma developing in extragonadal endometriosis are
      presented. Each case had a different clinical course. In addition to routine
      histopathologic studies immunohistochemical studies to assess the expression of
      cytoceratin and glycoprotein CD-44 were performed. In both cases CK-7 expression
      was higher in malignancy then in the endometrioid tissue. Very high expression of
      CD-44 protein (marker of metastatic potential) was found in patients with poor
      progress of the disease.

PMID- 12185708
TI  - [Thoracoventropagus: case presentation].
AB  - Conjoined twinning is a rare event occurring once in every 50,000 to 100,000 live
      births as a result of incomplete fission of the embryonic disc before the 3rd
      week of pregnancy. Conjoined twins are classified according to the area of union,
      the most common site being the chest and the upper abdomen. We report the case of
      thoracoventropagus diagnosed prenatally and on the postnatal course. Other types
      of conjoined twins with regard to coexisting anomalies, management and prognosis
      are discussed.

PMID- 12185709
TI  - [Efficiency and safety of magnesium sulfate treatment in obstetrics].
AB  - Current views on efficacy and safety of magnesium sulfate treatment in obstetrics
      are presented. Negative effects of MgSO4 on fetus and newborn are described.
      Contradictory reports dealing with tocolytic efficacy of magnesium sulfate are
      discussed.

PMID- 12185710
TI  - [The role of chlamydia trachomatis infection in CIN and cervical cancer
      development].
AB  - The paper contains a review of the literature on the correlation between
      Chlamydia trachomatis infection and CIN as well as invasive cervical cancer. This
      infection is not only responsible for inflammation (very often occult) in the
      upper genital tract and PID but also is probably one of the causes of cervical
      hypertrophy. In high percentage of CIN Chlamydia trachomatis infection is
      present. This pathogen especially serotype G, I and D is strongly associated with
      development of invasive cervical cancer.

PMID- 12185711
TI  - [Reasons for the high perinatal mortality rate in Wielkopolska Region based on
      data from the Mother and Child Health Institute].
AB  - Contribution to prepare present paper were extremely unsatisfied result of
      perinatal mortality rate in Wielkopolska, the region in which for many years
      efficiently works three-level perinatal care system and exists high class III
      level center. The main reasons of such situation Authors suspect in incorrect
      full filling of rapport forms prepared by maternal hospitals in Poland and in
      interpretation coming only just from 70% Polish hospitals performing care over
      mother and newborn. We suggest also, that estimation of perinatal mortality
      should take place after elimination of number of deaths due to developmental,
      lethal defects and malformations, classified in accordance with ICD-10 code.

PMID- 12185712
TI  - [Expression of intercellular adhesion molecule-1 (ICAM-1) on the surface of
      peripheral blood lymphocytes of pregnant women with pregnancy-induced
      hypertension].
AB  - OBJECTIVES: Intercellular adhesion molecule-1 (ICAM-1, CD54) is involved in
      process of leukocytes adhesion to endothelium as well as in their migration to
      surrounding tissues. There is much evidence that pregnancy-induced hypertension
      (PIH) presents a state of endothelial destruction mediated partially by increased
      ICAM-1 expression on endothelial cells and neutrofils. DESIGN: The aim of this
      study was to evaluate the expression of ICAM-1 (CD54) molecule on the peripheral
      blood lymphocytes of pregnant women with PIH studied "in vitro". MATERIALS AND
      METHODS: Preeclampsia (PE) and transient hypertension (TH) were defined according
      to USA National Health Institute criteria. The study group consisted of 16 women
      with preeclampsia (PE), 12 women with transient hypertension (TH) and 9 women
      with physiological pregnancy. The group of 8 nonpregnant women served as
      controls. Exclusion criteria were: uterine contractions, infection and steroid
      therapy before blood sampling. Peripheral blood was obtained by venipuncture.
      Lymphocytes were isolated and cultured by using standard procedures. Mitogenic
      doses of phytohaemaglutynin (PHA) were added to each culture. Immunofluorescent
      marking techniques with anty-CD54 one-step monoclonal antibodies were performed.
      Analysis was made with FACSCalibur flow-cytometer with 488 nm argon laser using
      CellQuest programme. The results were described as the percentage of CD54+
      lymphocytes and MFI index corresponding density of CD54 molecules on the
      lymphocyte surface. Statistical analysis was performed using t-Student and U-Mann
      Whitney tests. The work was sponsored by KBN 4 P05E 118,15 grant. RESULTS: The
      percentage of CD54+ lymphocytes in physiological pregnancy compared to
      nonpregnant women did not differ significantly (56.9 +/- 20.8% vs. 57.2 +/-
      14.0%, p = 0.97). The MFI value was increased in pregnant women but in comparison
      with nonpregnant women did not reach statistical significance (34.7 +/- 35.7 vs.
      17.8 +/- 4.3, p = 0.20). The percentage of CD54+ lymphocytes in TH group compared
      to normal pregnant women did not differ significantly (52.2 +/- 18.6% vs. 56.9 +/
      20.8%, p = 0.58) but MFI value was significantly increased (100.6 +/- 81.5 vs.
      34.7 +/- 35.7). In PE group compared to normal pregnant women the percentage of
      CD54+ lymphocytes as well as MFI value were significantly increased (CD54+: 70.8
      +/- 12.9% vs. 56.9 +/- 20.8%, p < 0.05; MFI: 170.8 +/- 91.7 vs. 34.7 +/- 35.7, p
      < 0.0005). CONCLUSIONS: 1/expression of ICAM-1 molecule on peripheral blood
      lymphocytes studied "in vitro" during normal pregnancy is not different in
      comparison to the nonpregnant state, but 2/ in pregnancy complicated with PIH is
      significantly increased, especially in PE, 3/described changes are a sign of the
      lymphocyte activation and may be responsible for endothelial destruction observed
      in PIH.

PMID- 12185713
TI  - [Selected parameters of mechanical ventilation of the newborn infants after PDA
      surgical ligation].
AB  - In the above study we introduced initial results of pulmonary function
      measurements (PFM) in newborns with respiratory distress syndrome, after a
      surgical ligation of persistent ductus arteriosus (PDA). Material comprised seven
      newborns admitted in Department of Neonatology University of Medical Sciences in
      Poznan. Mean birth weight of our patient was 1072.9 +/- 187.1 g, and average
      maturity was 27.0 +/- 1.6. Diagnosis of PDA was established on the basis of
      clinical and Doppler examination. PFM was carried out with pneumotachometric
      method by VenTrak station immediately before and during 24 hours after the
      surgical intervention. Only mechanical breaths were analysed. We noted
      significantly higher values of dynamic compliance (Cdyn) and lower mean airways
      pressure (MAP) after ligation of PDA. The drop of resistance of airways (Raw) was
      small and had no statistical value.

PMID- 12185714
TI  - [Analysis of factors influencing the cord blood sample collection for clinical
      purposes].
AB  - The survival rate of patients after cord blood transplantation depends on the
      number of nucleated cell transplants. The number of nucleated cells available for
      transplantation closely correlates with collected volume of cord blood. The
      influence of several obstetric factors on the volume of cord blood donation was
      investigated. Cord blood was obtained from 32 normal full-term deliveries. Length
      of gestation, age of mother, weight of placenta and length of umbilical cord were
      analysed for their impact on the volume of cord blood. Mean volume of collected
      cord blood was 103 ml. We did not establish the correlation between the volume of
      collection and the weight of placenta (measured after blood collection), the
      length of gestation and the age of mothers. A close and significant correlation
      (p < 0.05, r = 0.78) concerned the length of umbilical cord and the volume of
      cord blood donation. Length of umbilical cord is the parameter which may be
      useful for selection of the most promising cases in the collection of cord blood.

PMID- 12185715
TI  - Endothelin-1 (ET-1) as a mediator of pregnancy induced hypertension (PIH).
AB  - Pregnancy induced hypertension (PIH) is accompanied by injury and further
      activation of placental endothelial cells. Activated endothelial cells produce
      several mediators, among them endothelin-1 (ET-1)--one of the most potent
      vasoconstrictors. The aim of the study was to examine the ET-1 level in serum of
      18 women with PIH and compare it to the group of 16 normotensive pregnant women.
      ET-1 level, as evaluated by ELISA test, was significantly higher in PIH than in
      normotensive pregnancy, 33.00 +/- 12.07 vs. 25.00 +/- 5.69 pg/mL (p = 0.005),
      respectively. It might be concluded, that ET-1 level is a prognostic parameter,
      indicating the possibility of PIH development.

PMID- 12185716
TI  - [Elevated level of CA 125 antigen in women in reproductive age without neoplastic
      diseases in pelvis minor].
AB  - Behaviour of CA 125 antigen in women in reproductive age without neoplastic
      diseases in pelvis minor was presented. The study material was divided into 4
      groups: 29 women with endometriosis, 16 women with inflammation of pelvis minor,
      7 women with cirrhosis, developmental malformation of reproductive organs and
      pregnancy, 8 women of middle gynaecological age 6.75 had endometriosis. It has
      been revealed that the inflammatory state of the uterine adnexa and the appendix
      as well as cirrhosis, developmental malformation of reproductive organs may
      evolve with elevated level of CA 125 marker. It has also been shown that
      endometriosis in pelvis minor may be expressed by a raised level of CA 125
      marker.

PMID- 12185718
TI  - [Urine iodine excretion by healthy pregnant women after vitamin and microelement
      supplementation (Materna) in the first trimester].
AB  - OBJECTIVES: The aim of the study was the assessment of iodine turnover in healthy
      pregnant women supplemented by microelement and vitamin preparation Materna.
      METHODS: To assess iodine supplementation, a modified PAAM method was used for
      measurement of iodine concentration in morning urine. MATERIALS: 50 pregnant
      healthy women were tested for Materna supplementation. Urine iodine concentration
      was measured starting from the I trimester of pregnancy and then after 1, 2 and 3
      months of Materna administration. RESULTS: It has been found, that 3 months of
      supplementation with Materna reduces iodine deficiency in 83% of primiparas,
      while in the same time urine iodine concentration was normal in only 30% of women
      in their third and next pregnancy. CONCLUSION: In our opinion iodine urine
      concentration should be assessed in all multiparas using Materna after 1 month of
      supplementation in order to correct individual iodine supplementation doses.

PMID- 12185717
TI  - [Relationship between estrogen, progesterone, total testosterone,
      androstenedione, and epidural growth factor in blood and breast cyst fluid].
AB  - In breast cyst fluid obtained from 50 patients age (47.1 +/- 2.3) sodium,
      potassium, oestrone (E1), oestradiol (E2) androgens, progesterone, (P) and
      Epidermal Growth Factor--EGF were determined. Markedly higher oestrogens,
      progesterone, testosterone, and EGF-levels were detected in cyst fluid than in
      blood. These data have confirmed previous results and have clearly shown that
      breast cyst fluid with high potassium (ratio K/Na > 1.0) contains more
      oestrogens, progesterone, testosterone, androstenedione and EGF than the group
      with low electrolyte ratio. This finding might be put in correlation with the
      fact that patients with high ratio K/Na may a higher risk of breast cancer than
      those with low electrolyte ratio.

PMID- 12185719
TI  - [Carcinoid of the appendix coexisting with inflammatory tumor of left adnexa. A
      case report].
AB  - A very rare case of appendix carcinoid in a patient operated for left pyosalpinx
      was presented. On the basis of literature review and the patient's complaints
      there is no unequivocal evidence indicating relationship between occurrence of
      carcinoid and pyosalpinx of adnexa in the patient. Check-up examination of
      appendix is recommended in laparotomy, and appendectomy or hemicolectomy in case
      of carcinoid suspicion must be performed.

PMID- 12185720
TI  - [Anorexia nervosa in woman with Turner's syndrome].
AB  - The authors report a case of anorexia nervosa in woman with Turner's syndrome
      (45, X). In this case there was a low blood concentration of LH and FSH, and
      there was a lack of reaction to intravenous administration of 100 micrograms of
      GnRH. Partial syndrome of "empty sella" was found in a presented case by use of
      magnetic resonance imaging. There was a connection between the onset of anorexia
      nervosa and the tragic death of the patient's father. The inconsiderate start
      with HRT aggravated a course of a anorexia nervosa. The authors considered the
      plausible existence of relations between "empty sella" and the development of
      anorexia nervosa.

PMID- 12185721
TI  - [A case of multiple malignancies].
AB  - A case of fourfold cancer: of the vulva and larynx diagnosed synchronously and
      the breast and lung diagnosed metachronously is presented.

PMID- 12185722
TI  - [Smoking in pregnancy--long term effect].
AB  - OBJECTIVES: The data review on the cancer risk in children exposed to tobacco
      smoke in utero. MATERIALS AND METHODS: The analysis was based on databases
      available in Medline, Cancerlit and Cochrane. RESULTS: The reviewed data confirm
      that the risk of developing malignancy after the exposure to maternal smoking is
      low. Nevertheless, some publications point to a higher risk of having brain
      tumors or leukemias. CONCLUSIONS: Together with facts that fetus is jeopardized
      with toxic metabolites of tobacco smoke which cause genotoxic effects or DNA
      adducts give additional arguments the necessity of introducing smoking cessation
      programs in perinatal care.

PMID- 12185723
TI  - [Antiphospholipid syndrome in obstetrics--a new version of criteria,
      pathomechanism and the prophylaxis].
AB  - The paper surveys literature referring to criteria of the antiphospholipid
      syndrome in obstetrics as well as to the pathomechanism and prophylactic
      treatment. Criteria of that syndrome were modified in 1999. Generally accepted
      are two clinical criteria--thromboembolic complications and recurrent pregnancy
      loss, as well as two laboratory criteria--presence of lupus anticoagulant and/or
      anticardiolipin antibodies in the medium or high titer. Thrombocytopenia is no
      longer treated as a criterion. Diagnosis is formulated on the basis of at least
      one clinical and one laboratory criterion. It is assumed that obstetric
      complications are the result of immunological reaction of antiphospholipid
      antibodies with antigen located in trophoblast or vascular endothelium of the
      spiral arteries. The elimination of the activity of placental anticoagulant-
      annexin V--is the main mechanism of local thrombosis and infractions in placenta.
      Improvement in the results of obstetrics care can be achieved through
      prophylactic treatment: from the beginning of pregnancy until delivery,
      acetylosalicylic acid (aspirin) is applied in low doses, i.e. 80 mg/24 h and low
      molecular weight heparin or standard heparin in low-doses. It is recommended that
      for 6 weeks after delivery oral anticoagulants should be used in prophylactic
      doses in cases of primary syndrome, and in the secondary syndrome even constant
      antithrombotic prophylaxis is advised.

PMID- 12185724
TI  - [Application of skin glue in wound repair after laparoscopy].
AB  - The aim of the study was to evaluate the usefulness of skin glue--Dermabond in
      wound repair after laparoscopy intervention. It is a new adhesive with the
      physical properties that differ from other cyanoacrylate adhesives and give a
      significantly greater tensile strength. It was proved to have similar cosmetic
      results in the repair of lacerations and incisions when compared with those
      closed with monofilament sutures. Octylcyanoacrylate tissue adhesive has been
      approved for clinical use by the Health Protection Branch of Health Canada and
      has been approved for clinical trials by the U.S. Food and Drug Administration.
      The study was conducted on thirty women with use of skin glue in wound closure
      after laparoscopy. Thirty-five patients served as controls whose skin was closed
      with a monofilament suture by standard sterile techniques. We estimated local
      tissue reaction, way of healing and cosmetic results. There was no difference in
      healing found in this study between the two examined groups. The only significant
      correlation outcome measures was in a very good cosmetic effect in the group
      where skin glue (p = 0.0231) was applied. The authors suggest high usefulness of
      Dermabond glue in good wound closure and correct healing.

PMID- 12185725
TI  - [Dental health of adults in the Zurich Canton].
AB  - In 1992 and 1999, dental health in 20- to 79-year-old adults from the canton of
      Zurich was assessed with a standardized method (WHO). The aim was to establish
      the current state and changes of dental health. Roughly half of the 852
      approached adults selected by chance did take part. In 1992 and 1999, the mean
      number of unfilled, decayed teeth (DT) was on a low level in all age classes (0.2
      to 1.8 depending on age class and examination year). The number of missing teeth
      (MT) in older adults (60-79) was on a high level (8.8 to 13.4). The number of
      filled teeth (FT) was highest (14.8 to 16.2) in middle-aged adults (40-59). Total
      loss of teeth was found only in older adults (60-79). Lack of a "functional" own
      dentition (5 teeth present in each quadrant) was found in roughly half of the 60-
      to 69-year-olds and two thirds of the 70- to 79-year-olds. In 1999, the state of
      the roots and loss of attachment was assessed. Wedge-shaped defects were found in
      more than half of the middle-aged adults (40-59). Carious roots were found in
      more than half of the 70- to 79-year-olds. Nearly half of the 70- to 79-year-old
      participants showed "severe" loss of attachment (> or = 6 mm). In the short
      period from 1992 to 1999, a significant decrease of 3.7 DMFT was found in 20- to
      49-year-old adults. The decrease of 0.9 MT and 2.1 FT means also a decrease in
      treatment need in this age segment. In contrast, in the 50- to 79-year-olds no
      change in dental health could be established.

PMID- 12185726
TI  - [The operating microscope in dental practice: minimally invasive restorations].
AB  - With the visualization provided by the operating microscope (OM), it is now
      possible to place fillings in formerly inaccessible areas and work in a way that
      preserves the most enamel and/or dentin. The OM enables working with full
      overview in interdental areas or in hard-to-reach areas around crowns. The good
      view not only enables new forms of therapy, but reduces stress while working. The
      two clinical cases cited show clearly how the OM can be used advantageously in a
      range of situations--from the economical repair of a large old filling to minimal
      invasive initial treatment. As an added bonus, the OP allows a completely relaxed
      and upright working posture.

PMID- 12185727
TI  - [Three-dimensional measurement of symmetry using laser-generated models].

PMID- 12185729
TI  - [Enterprise research].

PMID- 12185728
TI  - [National insurance and the society].

PMID- 12185730
TI  - [Follow-up of sick-listed--unsuccessful strategy?].

PMID- 12185731
TI  - [Fainting].

PMID- 12185732
TI  - [Autopsies and suicide among the elderly].

PMID- 12185733
TI  - [Suicide among the elderly in Norway].
AB  - BACKGROUND: We wanted to generate more knowledge about elderly people who commit
      suicide in Norway, especially in relation to demographic conditions, somatic and
      psychiatric disease, suicide methods and suicidal communication. MATERIAL AND
      METHODS: The material consists of 287 cases of suicide in people aged 65 years or
      more who were examined at the Department of Forensic Medicine of the University
      of Oslo during the 1992-2000 period. Sources of information were the forensic
      autopsy records and police reports. RESULTS: In a majority of the cases the
      deceased had suffered from psychiatric disease (62%), mostly depression (41%).
      Somatic disease was less often a prominent factor (22%). A majority had an
      established contact with the health services at the time of suicide. Suicidal
      thoughts had been expressed by 29%; previous suicide attempts had been reported
      by 15%. INTERPRETATION: Health personnel must pay attention to elderly people
      with symptoms of depression, especially those who express suicidal feelings and
      have made previous attempts.

PMID- 12185734
TI  - [Benign paroxysmal positional vertigo].
AB  - BACKGROUND: Benign paroxysmal positional vertigo is a disorder of the inner ear
      causing brief attacks of intense rotatory vertigo and nystagmus occurring shortly
      after certain well-defined head movements. The present review discusses treatment
      of this disease in relation to new knowledge about its epidemiology and
      pathogenesis. MATERIAL AND METHODS: A review is given based on our experience and
      a Medline search of relevant literature published over the last ten years.
      RESULTS: The disorder is common; prevalence increases with age. There is now
      general agreement that the symptoms are caused by loose particles in the
      endolymph of the inner ear. Treatment by repositioning manoeuvres has proven
      effective. INTERPRETATION: Treatment of benign paroxysmal positional vertigo is
      safe, effective, and inexpensive. It should start at the time of diagnosis.
      Management of typical cases should be feasible in a general practice setting.

PMID- 12185735
TI  - [Treatment of acoustic neuroma].
AB  - BACKGROUND: Acoustic neuroma is the most common tumour in the cerebello-pontine
      angle. MATERIAL AND METHODS: We present the results after surgery in 99 cases,
      and the natural course of the disease in 82 patients followed for up to 20 years
      (mean 3 years). RESULTS: During the observation period, 43% of the tumours
      increased in size. 36% of patients suffered increasing hearing loss. Total
      removal was accomplished in 92 cases. In 12 cases hearing preservation was
      attempted; successfully in five cases. 72 patients had normal or near normal
      postoperative facial nerve function, whereas 19 patients got a facial nerve
      paralysis. Two patients died, one because of haemorrhagic infarction and
      cerebellar swelling, and one because of ventricular fibrillation. Five patients
      had to be reoperated for CSF leakage. INTERPRETATION: Acoustic neuroma treatment
      is still a challenge. We favour a team approach to treat this condition.

PMID- 12185736
TI  - [Lead poisoning--a case report].
AB  - Lead poisoning may cause irreversible health defects, including anaemia, central
      nervous system problems and various organ defects. We describe a patient with
      lead poisoning. A 54-year-old woman was admitted to hospital with anaemia and
      unspecific gastrointestinal symptoms. Peripheral blood smear and bone marrow
      aspirate showed basophilic stippling of erythrocytes suggestive of lead
      poisoning, which was confirmed by high concentrations of lead in her blood. The
      lead source was the glazing of a ceramic wine jug. Chelating therapy was started.
      Haemoglobin was normalised; the patient returned to work after nine months.
      Correct diagnosis and treatment can prevent serious health problems caused by
      lead poisoning.

PMID- 12185737
TI  - [Lead poisoning--an overview].
AB  - MATERIAL AND METHODS: We present a review of the history, pathophysiology,
      diagnosis and treatment of lead poisoning based on relevant literature. RESULTS
      AND INTERPRETATION: The human body does not metabolize lead, and lead
      accumulation may cause organ failure. Lead poisoning may cause serious health
      defects, including anaemia, central nervous system problems and various organ
      defects. Sources of lead may be found in the home as well as in the workplace or
      elsewhere in our environment, but lead poisoning is an infrequent condition.
      Prevention is important, but manifest lead poisoning can be treated effectively.

PMID- 12185738
TI  - [Progesterone cream--efficient in premenstrual syndrome and climacteric
      problems?].

PMID- 12185739
TI  - [Medical and non-medical risk factor criteria for disability pension].
AB  - BACKGROUND: Non-medical factors may contribute substantially to the risk of
      becoming disabled, despite the common medically based criteria for disability
      pension. This study seeks to identify medical and non-medical determinants for
      the national medically-based disability pension in a Norwegian total population.
      MATERIAL AND METHODS: The baseline data were obtained through a comprehensive
      health screening programme, the Nord-Trondelag Health Study in 1984-86 (HUNT I).
      Participants were people without disability pension, 20-66 years old in 1984-86.
      Information on disability pensioning was obtained from the National Insurance
      Administration database in 1995. Data analysis was performed by life table and
      Cox regression analysis. RESULTS: The incidence of disability pension showed
      great variations by age and gender; there was an increase over the follow-up
      period, especially among people below 50. We found a consistent pattern of
      increasing risk of disability pension with decreasing socio-economic status and
      education. Low educational level, low perceived health, occupational related
      factors, and any long-standing health problem were found to be the strongest
      independent risk factors for disability pension. INTERPRETATION: Non-medical
      factors are strong risk factors for disability pension. These factors are usually
      not addressed by individually based health or rehabilitation programmes. Thus,
      when it comes to addressing the causes of incidence of disability pension in the
      population, the results suggest a population approach.

PMID- 12185740
TI  - [What explains the growth of national insurance expenditure for primary health
      care?].
AB  - BACKGROUND: Fee-for-item payments are the main source of remuneration for primary
      care physicians in Norway. Physicians receive a major part of these payments from
      the National Insurance Administration. The present study describes the
      development in the National Insurance Administration expenditure for primary
      physician services in Norway from 1990 to 2000. MATERIAL AND METHODS: The
      analyses were performed on accounting data from the National Insurance
      Administration and data on the number of physician per 10,000 population from
      Statistics Norway. RESULTS: From 1990 to 2000, expenditure increased by 84%, from
      NOK 863.8 million to NOK 1.58 billion. Our main finding is that a substantial
      part of this increase can be explained by increases in the number of primary care
      physicians, population size, and the level of fees. INTERPRETATION: One
      interpretation of our findings is that National Insurance Administration
      expenditure on primary physician services to some extent can be controlled by
      regulating the number of physicians practicing with reimbursement from the
      National Insurance Administration and the level of fees.

PMID- 12185741
TI  - [Decisions of the National Insurance Court related to personality disorders 1986
      2001].
AB  - BACKGROUND: During the past decades, much clinical research in psychiatry has
      been devoted to personality disorders. The aim of the present study was to
      examine whether recent experience in this area has influenced the decisions in
      cases appealed to the National Insurance Court. MATERIAL AND METHODS: The study
      includes cases recorded in the court database over the period 1986-2001. This
      database contains information on decisions with diagnoses classified according to
      ICD-9 and ICD-10. RESULTS: The court issued 159 decisions in cases with
      personality disorder as the main diagnosis, some associated with other
      psychiatric co-morbidity (19%), with alcohol and drug abuse (25%), and with
      somatic illness (16%). 57% of the cases were related to disability pension
      claims. The proportion of rulings in favour of the complaining party increased
      from 18% to 79%. The total number of court rulings rose from 2,386 in 1986 to
      5,762 in 2001. The proportion of decisions in favour of the complaining party
      increased more for personality disorders than for other diagnostic groups such as
      neurosis and somatic conditions. INTERPRETATION: In recent years a broader
      concept of illness has won acceptance and a clearer clinical definition of
      personality disorders has been developed. The National Insurance Court has
      contributed to the definition of legal guidelines at the crossroads of medicine
      and social dysfunction.

PMID- 12185742
TI  - [Norwegian research concerning health and social insurance].

PMID- 12185743
TI  - [Epilepsy and sudden death].

PMID- 12185744
TI  - [Anaphylaxis and food hypersensitivity].

PMID- 12185745
TI  - New liquid chromatography/electron ionization mass spectrometry methods in water
      analysis.
AB  - A method to extract and analyze organic compounds from water is presented. A
      solid phase micro-trap (micro-SPE) directly connected to the micro-analytical
      column is used. Sensibility and specificity needed for trace analysis are
      guaranteed by mass spectrometric electron ionization (EI) detection. A new micro
      HPLC/EI-MS interface called Capillary-EI (Cap-EI) is described. The ultimate
      evolution of this interface is also presented: in this extremely simplified
      interface the analytes are nebulized, vaporized and ionized in the small volume
      of the ion source. This interface, called Direct-EI, exploits nano- and micro
      HPLC columns with a mobile phase flow rates ranging from 0.3 to 1.5 microL/min.
      Contemporary use of micro SPE, Cap-EI or Direct-EI gives us a powerful technique
      to identify and quantify organic pollutants at part per billion level (ppb).

PMID- 12185746
TI  - Global migration from styrenics to liquid food simulants.
AB  - Chemical inertness of typical styrene polymers used in food packaging was
      investigated by "global migration" measurements. Absorption of liquid food
      simulants by plastics was also studied. Migrated compounds, detected and
      identified by gaschromatography-mass spectrometry (GC-MS), are styrene (monomer)
      and styrene dimers. All migration values, measured under different experimental
      conditions, turn out to be lower than the overall migration limit, as fixed by
      current legislation.

PMID- 12185747
TI  - Trimethoxysilylpolymethacrylate as new material for stone conservation.
      Porosimetric and colorimetric investigations.
AB  - Aimed to obtain new materials for the conservation of stone substrates, we report
      here on the synthesis of a polymer which has been obtained by inducing
      polymerization on a methacrylate monomer functionalized by alchoxysilane groups.
      Two lithotypes, the Comiso calcarenite and Mistretta quartzite, stones largely
      used in artworks of north-eastern Sicily, were treated with the above polymer and
      its conserving efficacy evaluated in terms of porosimetric features, hydric
      properties and appearance. The collected data were compared to those provided,
      under the same experimental conditions, by an
      ethylmethacrylate/methylmethacrylate copolymer and an alkylalchoxysilane,
      products widely employed in the protection of stones. Experiments aimed to test
      the durability of the above polymer against UV artificial ageing are also
      reported.

PMID- 12185748
TI  - On the complex formation equilibria between iron (III) and sulfate ions.
AB  - The equilibria have been investigated at 25 degrees C in 3 M NaClO4 using
      potentiometry, glass and redox Fe3+/Fe2+ half-cells, and UV optical
      absorptiometry. The concentration of the reagents was chosen in the intervals:
      10(-4) < or = [Fe(III)] < or = 5.10(-3) M, 0.01 < or = [SO4(2-)]tot < or = 0.65
      M. The value of [H+] was kept at 0.1 M or more to reduce the hydrolysis of the
      Fe3+ ion to less than 1%. Auxiliary constants, corresponding to the formation of
      Fe(II)-sulfate complexes and to the association of H+ with SO4(2-) ions, were
      taken from previous determinations. The experimental data could be explained with
      the equilibria [formula: see text] Equilibrium constants at infinite dilution,
      log beta 101 degrees = 3.82 +/- 0.17, log beta 102 degrees = 5.75 +/- 0.17 and
      log beta 111 degrees = 3.68 +/- 0.35, have been evaluated by applying the
      specific interaction theory.

PMID- 12185749
TI  - Hydroxo sulfate complexes of iron (III) in solution.
AB  - The ternary Fe (III)-OH(-)-SO4(2-) complexes have been investigated at 25 degrees
      C in 3 M NaClO4 by potentiometric titration with glass electrode. The metal and
      sulfate concentrations ranged from 2.5 x 10(-3) to 0.03 M and from 5.10(-3) to
      0.060 M, respectively. [H+] was decreased from 0.05 M to incipient precipitation
      of basic sulfate which occured at log[H+] between -2.3 and -2.5 depending on the
      concentration of the metal. For the interpretation of the data stability
      constants of HSO4(-), of binary hydroxo complexes (FeOH2+, Fe(OH)2+,
      Fe2(OH)2(4+), Fe3(OH)4(5+), Fe3(OH)5(4+)) and of sulfate complexes (FeSO4+,
      FeHSO4(2+), Fe(SO4)2-) were assumed from independent sources. The data are
      consistent with the presence of FeOHSO4, log beta 1-11 = -0.49 +/- 0.03.
      Equilibrium constants are defined as beta pqr for pFe3+ +qH+ +rSO4(2-) [symbol:
      see text] FepHq(SO4)r3p+q-2r. No substantial better fit could be found by adding
      a second mixed complex. Only a slightly smaller agreement factor resulted
      introducing as minor ternary complex Fe3(OH)6(SO4)3(3-) with log beta 3-63 = -5.8
      +/- 0.5. Its evidence, however, cannot be considered conclusive.

PMID- 12185750
TI  - Lead removal and recovery from battery industry wastewaters by soluble starch
      xanthate.
AB  - Treatment, removal and recovery of lead (3 mg/L) from battery industry
      wastewaters have been investigated utilising a chemical precipitation process
      with soluble starch xanthate (SX) at pH 5-6. A reactant ratio, i.e., SX/Pb(II) =
      6 mol/mol, a reaction time of 15 min., the addition of 15 mg/L of a cationic
      polyelectrolyte and a final filtration gave residual lead concentrations in the
      liquid phase less than 0.2 mg/L, well below the maximum limit established by the
      EU Directive. Lead was extracted from the obtained sludge by oxidation with
      sodium hypochlorite or hydrogen peroxide solutions. The amounts of oxidant needed
      were quantified as 13.5 mol NaClO/mol Pb and one order of magnitude larger, for
      H2O2, the latter due to the competitive disproportion reaction of the oxidant.
      The metal extraction was quantitative using sodium hypochlorite; when hydrogen
      peroxide was used, the formation of insoluble PbSO4 (Anglesite) gave a 80% metal
      extraction. In both cases molar ratios between sulphate and lead ions in the
      extracted solutions were in the range 2.1-2.2, in agreement with the
      stoichiometries of the reactions. Lead can be quantitatively recovered from the
      extracted (NaClO) solutions, for reuse, after a chemical precipitation process
      with 1M NaOH at pH 9-9.5, in the form of hydrocerussite [Pb3(CO3)2(OH)2].

PMID- 12185751
TI  - Data, knowledge and method bases in chemical sciences. Part IV. Current status in
      databases.
AB  - Computer readable databases have become an integral part of chemical research
      right from planning data acquisition to interpretation of the information
      generated. The databases available today are numerical, spectral and
      bibliographic. Data representation by different schemes--relational, hierarchical
      and objects--is demonstrated. Quality index (QI) throws light on the quality of
      data. The objective, prospects and impact of database activity on expert systems
      are discussed. The number and size of corporate databases available on
      international networks crossed manageable number leading to databases about their
      contents. Subsets of corporate or small databases have been developed by groups
      of chemists. The features and role of knowledge-based or intelligent databases
      are described.

PMID- 12185752
TI  - Interaction of alkyltin(IV) compounds with ligands of interest in the speciation
      of natural fluids: carboxylate and hydroxycarboxylate complexes of
      monomethyltin(IV) trichloride.
AB  - The formation and stability of some carboxylate and hydroxycarboxylate (acetate,
      1,2,3-propanetricarboxylate, 1,2,3,4-butanetetracarboxylate, malate and citrate)
      complexes of monomethyltin trichloride was studied potentiometrically at 25
      degrees C and at different ionic strengths in NaNO3 aqueous solution. The
      following quite stable species are formed in the different systems (M = CH3Sn3+):
      ML(OH)+, ML2(OH)0, ML(OH)2(0) and M2L(OH)5(0) for acetate; MLH+, ML0, ML(OH)- and
      ML(OH)2(2-) for propanetricarboxylate; MLH2+, MLH0, ML-, ML(OH)2- and ML(OH)2(3-)
      for butanetetracarboxylate; ML(OH)0, ML(OH)2- and ML(OH)3(2-) for malate; ML0,
      ML(OH)-, ML(OH)2(2-) and ML(OH)3(3-) for citrate. Hydroxycarboxylate complexes
      are significantly stronger than simple carboxylate ones and this is likely to be
      due to the interaction of the -OH group in citrate and malate with
      monomethyltin(IV), whose strength was also quantified. It was found that the
      stability of these complexes can be roughly expressed by the simple relationship
      log K = a zeta, where zeta is the product of the charges of reactants and log K
      is the equilibrium constant. For simple carboxylic ligands we have a = 1.8 +/-
      0.4 and, for hydroxycarboxylic ligands, a = 3.7 +/- 0.9. Other useful empirical
      relationships are reported. Moreover, hydroxycarboxylic complexes also play a
      prominent role in the speciation of monomethyltin(IV) under the pH conditions of
      interest for natural fluids.

PMID- 12185753
TI  - Extraction separation of thallium (III) from thallium (I) with n-octylaniline.
AB  - A novel method is developed for the extraction separation of thallium(III) from
      salicylate medium with n-octylaniline dissolved in toluene as an extractant. The
      optimum conditions have been determined by making a critical study of weak acid
      concentration, extractant concentration, period of equilibration and effect of
      solvent on the equilibria. The thallium (III) from the pregnant organic phase is
      stripped with acetate buffer solution (pH 4.7) and determined complexometrically
      with EDTA. The method affords the sequential separation of thallium(III) from
      thallium(I) and also commonly associated metal ions such as Al(III), Ga(III),
      In(III), Fe(III), Bi(III), Sb(III) and Pb(II). It is used for analysis of
      synthetic mixtures of associated metal ions and alloys. The method is highly
      selective, simple and reproducible. The reaction takes place at room temperature
      and requires 15-20 min for extraction and determination of thallium(III).

PMID- 12185754
TI  - Determination of tin (IV) in alloys and in canned food by visible
      spectrophotometric technique using pyrimidine azo compounds in presence of mixed
      surfactants.
AB  - The complex of tin (IV) with 5-(4'-nitro-2',6'-dichlorophenylazo) (I) and 5-(4'
      chlorophenylazo)-6-hydroxypyrimidine-2,4-dione (II) in the presence of nonyl
      phenoxy polyethoxyethanol (NPE) and cetyltrimethylammonium bromide (CTAB) has a
      sensitive absorption band with lambda max 517 and 488 nm, respectively. Under the
      optimal conditions, Beer-Lambert law is obeyed over the range 0.05-1.50 and 0.05
      1.30 micrograms ml-1 Sn(IV) with molar absorptivity being 9.50 x 10(4) and 1.05 x
      10(5) L mol-1 using ligand I and II, respectively. As compared with the visible
      methods which uses bromopyrogallol red (BPR) as the chromogenic reagent (lambda
      max = 550 nm) and that using phenylfluorone (lambda max = 360 nm), our method is
      highly sensitive and selective because the complexes have a high and sharp
      absorption band. In addition, the present method is simple and rapid, no heating
      or standing time is needed. By means of the mixed surfactants, the precipitation
      caused by the ion association of cetyltrimethyl-ammonium cation and I3- anion is
      avoided if iodide is used for separating micro amounts of tin(IV) from a sample
      matrix. An application of the proposed method to the determination of tin(IV) in
      a variety of alloys and in a canned food was made with satisfactory results.

PMID- 12185755
TI  - Polymerization of lanthanide acrylonitrile complexes.
AB  - The molecular complexes of some lanthanides scandium (Sc3+), yttrium (Y3+),
      lanthanum (La3+), gadolinium (Gd3+), cerium (Ce3+) and ytterbium (Yb3) have been
      studies in dimethyl formamide (DMF) spectrophtometrically equilibrium constants
      (K), molar extintion coefficient (epsilon), energy of transition (E) and free
      energy (delta G*) were calculated. The polymerization of acrylonitrile has been
      studied and investigated in the presence of Sc3+, Y3+, La3+, Gd3+, Ce3+, and Yb3+
      ions. The IR spectra of the formed AN-M (III) Br3 polymer complexes show the
      absence of the C identical to N band and the presence of two new bands
      corresponding to NH2 and OH groups. Magnetic moment values and the thermal
      stabilities of homopolymer and the polymer complexes were studied by means of
      thermogravimetric analysis and the activation energies for degradation were
      calculated.

PMID- 12185756
TI  - Charge transfer complexes of some anilides with nitrobenzene derivatives as pi
      electron acceptors.
AB  - The charge transfer complexes formed between some anilides and pi-electron
      acceptors [picric acid, 2,4-dinitrophenol, 3,5-dinitrobenzoic aicd, 3,5
      dinitrosalicylic acid and m-dinitrobenzene] are synthesized and characterized.
      Spectral characteristics and stability of the complexes are investigated and
      discussed in terms of donor molecular structure, pi-acceptor electron affinity,
      and solvent polarity. It is deduced that the complexes are mainly of the n-pi*
      and pi-pi* type where the ground state wave function can be described primarily
      by the non-bonding structure. The optimum conditions favouring the formation of
      the coloured complexes are extensively studied for the microdetermina-tion of
      anilides derivatives in pharmaceutical drugs using nitrobenzene as acceptor; the
      molecular structure was found to be 1:1 (D:A). Beer's law is obeyed up to 23.0,
      18.60 and 16.0 micrograms ml-1 for p(OH), p-(OCH3), and p-N(CH3)2, respectively.

PMID- 12185758
TI  - Case reports--functional imaging in epilepsy.

PMID- 12185757
TI  - Functional imaging in epilepsy.
AB  - Functional imaging plays a growing role in the clinical assessment and research
      investigation of patients with epilepsy. This article reviews the literature on
      functional MRI (fMRI) investigation of EEG activity, fMRI evaluation of cognitive
      and motor functions, magnetic resonance spectroscopy (MRS), single photon
      emission computed tomography (SPECT) and positron emission tomography (PET) in
      epilepsy. The place of these techniques in clinical evaluation and their
      contribution to a better neurobiological understanding of epilepsy are discussed.

PMID- 12185759
TI  - Epilepsy and pregnancy.
AB  - Pregnancies in women with epilepsy are high risk and need careful management by
      both the medical and obstetric teams due to the increased incidence of
      complications and adverse outcomes of pregnancy. By the time a pregnant woman
      with epilepsy presents, the foetus is virtually fully formed and the opportunity
      for altering drug treatment has passed. Women need to be counselled and told to
      seek advice about their anticonvulsant therapy should they wish to become
      pregnant. All major anticonvulsant drugs are teratogenic but the main risk to the
      developing foetus appears to be when the mother is on polytherapy especially if
      sodium valproate forms part of the combination. Folate supplements (5 mg) before
      conception are advisable. There appears to be a minor but significant increased
      risk of maternal complications in women with epilepsy such as hyperemesis
      gravidarum, pre-eclampsia and eclampsia, vaginal bleeding and premature labour.
      In the majority of women seizure control will not alter during pregnancy. Oral
      vitamin K should be given to the mother receiving enzyme-inducing antiepileptic
      drugs. POST-NATAL INFANT DEVELOPMENT: There is an increased risk of prematurity
      (9-11%), stillbirth, neonatal and perinatal death, haemorrhagic disease of the
      newborn, low Apgar scores and low birth weight (7-10%). BREAST FEEDING: Virtually
      all the anticonvulsant drugs are excreted in breast milk in low concentrations.
      Feeding difficulties, irritability and lethargy can occur. However, the benefits
      of breast feeding usually far outweigh any minor risks to the baby.

PMID- 12185761
TI  - Case reports.

PMID- 12185760
TI  - Epilepsy and the ovary (cutting out the hysteria).
AB  - This review touches on the historical links between epilepsy, seizures and the
      uterus and ovaries which have fascinated and misled physicians since Greco-Roman
      times. It then examines present knowledge of ovarian function and its effect on
      epileptic activity and vice versa before exploring the modern controversy about
      polycystic ovaries and the polycystic ovary syndrome, epilepsy and anticonvulsant
      medication. Based on present evidence, women with epilepsy are more prone to
      develop polycystic (polyfollicular) ovaries than other women due to the epilepsy
      itself. But women with epilepsy related polycystic (polyfollicular) ovaries are
      vulnerable to the effects of sodium valproate (possibly particularly during
      adolescence) and may develop the polycystic ovary syndrome: this is reversible if
      the valproate is withdrawn. Lamotrigine and carbamazepine seem to prevent the
      development of the syndrome.

PMID- 12185762
TI  - The 'number needed to treat' with levetiracetam (LEV): comparison with the other
      new antiepileptic drugs (AEDs).

PMID- 12185763
TI  - Area-selective stimulus-provoked seizures in post-anoxic coma.
AB  - We describe the case of a 70-year-old patient in whom hemiconvulsive seizures
      occurred during metabolic derangement, multiple stroke and post-anoxic coma
      following cardiac arrest. We employed the methods of clinical and EEG evaluation
      and CT brain scan. We found that hemiconvulsive seizures were provoked following
      a light tactile stimulus in the left-trigeminal area and occasionally a strong
      tapping in the right-trigeminal area. We conclude that this type of stimulus
      provoked seizure is extremely rare and could be explained by diffuse and severe
      brain damage.

PMID- 12185764
TI  - Bilateral fronto-occipital polymicrogyria and epilepsy.
AB  - We present a clinico-pathological case report in which both cortical dysplasia
      and epilepsy coexisted: a 30 year old male who was dead on arrival at hospital.
      One and a half hours earlier he had developed complex partial status with peri
      oral cyanosis. At post mortem examination his brain showed bilateral occipital
      frontal polymicrogyria with unlayered neuronal migration disorder; in other parts
      there were fourth layer migration disorders. The white matter exhibited
      multicystic encephalopathy. In the heart there was chronic interstitial and
      perivascular fibrosis, although he died of a cardiac arrest. Bilateral frontal
      occipital polymicrogyria is highly epileptogenic. This was a sporadic case and we
      cannot define a clear aetiology. There was a pathological cardiac condition
      without previous vascular risk factors which might be related to repetition of
      seizures and possibly to his sudden death during status epilepticus.

PMID- 12185765
TI  - Late-onset myoclonic epilepsy in Down's syndrome (LOMEDS).
AB  - The aim of this paper is to report a patient with late-onset myoclonic epilepsy
      in Down's syndrome (LOMEDS) as a differential diagnosis of adult-onset
      progressive myoclonic epilepsies. A 55-year-old male with Down's syndrome (DS) is
      described who developed progressively frequent myoclonus and generalized
      myoclonic-tonic seizures (GMTSs) at the age of 52. EEG recordings demonstrated
      background slowing and generalized polyspike-wave discharges occasionally
      associated with myoclonic jerks, leading to the classification of the primary
      generalized epileptic myoclonus. Descriptions of late-onset epilepsy in DS
      patients are rare. However, a review of the pertinent literature revealed at
      least two other cases of elderly DS patients developing progressive myoclonic
      epilepsy after the onset of dementia. We suggest that late-onset myoclonic
      epilepsy in Down's syndrome as characterized here should be considered in the
      differential diagnosis of adult-onset myoclonic epilepsies. LOMEDS apparently
      shares features with myoclonic epilepsy in Alzheimer's disease (AD) and
      Unverricht-Lundborg disease (ULD) caused by a mutation on chromosome 21. Since
      life expectation of DS patients has markedly increased, LOMEDS may be more
      frequent than currently acknowledged.

PMID- 12185766
TI  - The epidemiology of epilepsy: the size of the problem.
AB  - The prevalence of epilepsy is generally taken as between 5 and 10 cases per 1000
      persons, and the overall incidence as about 50 cases per 100,000 persons. The
      rates are dependent on case ascertainment and on definitions used. The prognosis
      depends on many factors, including the number of seizures at presentation, the
      seizure type and the use of anti-epileptic drugs. Epilepsy carries an excess
      mortality; the cause of death can be unrelated to epilepsy, related to the
      underlying disease causing epilepsy, or related to epilepsy itself.

PMID- 12185767
TI  - Vagus nerve stimulation for refractory epilepsy.
AB  - Vagus nerve stimulation (VNS) is a neurophysiological treatment for patients with
      medically or surgically refractory epilepsy. Since the first human implant in
      1989, more than 10,000 patients have been treated with VNS. Two randomized
      controlled studies have shown a statistically significant decrease in seizure
      frequency during a 12-week treatment period versus a baseline period when 'high
      stimulation' mode was compared with 'low stimulation' mode. The efficacy appears
      to increase over time. In general, one third of the patients show a > 50%
      reduction of seizure frequency; one third show a 30-50% seizure reduction, and
      one third of patients show no response. Few patients become seizure-free. Side
      effects during stimulation are mainly voice alteration, coughing, throat
      paraesthesia and discomfort. When studied on a long-term basis, VNS is an
      efficacious, safe and cost-effective treatment not only in adults but also in
      children and the elderly. The precise mechanism of action remains to be
      elucidated. In recent years much progress has been made through
      neurophysiological, neuroanatomical, neurochemical and cerebral blood flow
      studies in animals and patients treated with VNS. Further elucidation of the
      mechanism of action of VNS may increase its clinical efficacy and our general
      understanding of some physiopathological aspects of epilepsy. Finally, VNS may
      become an alternative treatment for other conditions such as depression and pain.

PMID- 12185768
TI  - Vagus nerve stimulation for refractory epilepsy.

PMID- 12185769
TI  - Surgery for epilepsy.
AB  - While medical treatment remains the first line of treatment for epilepsy, surgery
      provides effective long-term control in suitable patients. Detailed
      investigations are necessary to prove suitability and in order to choose the
      appropriate procedure. This article gives an outline of the investigative
      programme and the various operative approaches. Novel methods and those under
      investigation are also discussed.

PMID- 12185770
TI  - Surgery.

PMID- 12185771
TI  - Epileptogenic brain malformations: clinical presentation, malformative patterns
      and indications for genetic testing.
AB  - We review here those malformations of the cerebral cortex which are most often
      observed in epilepsy patients, for which a genetic basis has been elucidated or
      is suspected and give indications for genetic testing. There are three forms of
      lissencephaly (agyria-pachygyria) resulting from mutations of known genes, which
      can be distinguished because of their distinctive imaging features. They account
      for about 85% of all licence-phalies. Lissencephaly with posteriorly predominant
      gyral abnormality is caused by mutations of the LIS1 gene on chromosome 17.
      Anteriorly predominant lissencephaly in hemizygous males and subcortical band
      heterotopia (SBH) in heterozygous females are caused by mutations of the XLIS (or
      DCX) gene. Mutations of the coding region of XLIS were found in all reported
      pedigrees, and in most sporadic female patients with SBH. Missense mutations of
      both LIS1 and XLIS genes have been observed in some of the rare male patients
      with SBH. Autosomal recessive lissencephaly with cerebellar hypoplasia has been
      associated with mutations of the reelin gene. With few exceptions, children with
      lissencephaly have severe developmental delay and infantile spasms early in life.
      Patients with SBH have a mild to severe mental retardation with epilepsy of
      variable severity and type. X-linked bilateral periventricular nodular
      heterotopia (BPNH) consists of typical BPNH with focal epilepsy in females and
      prenatal lethality in males. About 88% of patients have focal epilepsy. Filamin A
      (FLNA) mutations have been reported in some families and in sporadic patients.
      Additional, possibly autosomal recessive gene(s) are likely to be involved in
      causing BPNH non-linked to FLN1. Tuberous sclerosis (TS) is a dominant disorder
      caused by mutations in at lest two genes, TSC1 and TSC2. 75% of cases are
      sporadic. Most patients with TS have epilepsy. Infantile spasms are a frequent
      early manifestation of TS. Schizencephaly (cleft brain) has a wide anatomo
      clinical spectrum, including focal epilepsy in most patients. Familial occurrence
      is rare. Heterozygous mutations in the EMX2 gene have been reported in some
      patients. However, at present, there is no clear indication on the possible
      pattern of inheritance and on the practical usefulness that mutation detection in
      an individual with schizencephaly would carry in terms of genetic counselling.
      Amongst several syndromes featuring polymicrogyria, bilateral perisylvian
      polymicrogyria had familial occurrence on several occasions. Genetic
      heterogeneity is likely, including autosomal recessive, X-linked dominant, X
      linked recessive inheritance and association to 22q11.2 deletions. FISH analysis
      for 22q11.2 is advisable in all patients with perisylvian polymicrogyria. Parents
      of an affected child with normal karyotype should be given up to a 25% recurrence
      risk.

PMID- 12185772
TI  - 'A systematic overview--a decade of research'. The information and counselling
      needs of people with epilepsy.
AB  - This paper explores the background to epilepsy in terms of medical impact and
      psychosocial effects. The argument that information and counselling may be
      central to the person with epilepsy is explored. The evidence from primary
      research published between 1990 and 2000 investigating the information and
      counselling needs of people with epilepsy is appraised and synthesized. This
      paper seeks to answer the following questions: What are the information and
      counselling needs of people with epilepsy? What are the preferred formats, timing
      and delivery of information and counselling? What are the outcomes of information
      giving and counselling for people with epilepsy? The review suggests that there
      are unmet needs for personal and general information about epilepsy which may
      include individual or group education and counselling. Information related to
      gaining control for people with epilepsy and targeted public education may
      contribute to improved quality of life for people with epilepsy. Information is
      required which is individually relevant and could be delivered in small groups or
      as part of an individual counselling service. Specialist epilepsy clinics and
      specialist nurses can improve patient knowledge and communication and provide an
      effective and high quality service for people with epilepsy.

PMID- 12185773
TI  - The epilepsy nurse specialist--expendable handmaiden or essential colleague?
AB  - The benefits of a specialist epilepsy nurse in the management of people with
      epilepsy are still in question. Evidence from controlled clinical trials suggests
      that patients supported by a nurse specialist are well informed and have a high
      degree of satisfaction. However, no significant effect on health status or the
      number of seizures has been yet demonstrated, although this is not the primary
      function of most epilepsy specialist nurses. The recent International League
      Against Epilepsy (ILAE) British Branch meeting in Liverpool (April 2001)
      dedicated a one-day symposium to epilepsy nursing including a debate on the
      effectiveness of 'the epilepsy specialist nurse--warm fuzzy feeling or evidence
      based?'. Although it was agreed that evidence-based research is limited, the case
      studies and data presented, throughout the symposium, highlighted the varying
      role of the epilepsy specialist nurse in supporting both the specialist physician
      in epilepsy care, the non-specialist physician and the primary care physician in
      patient communication. This paper provides an overview of the presentations given
      at the symposium, including those on nursing research and publishing.

PMID- 12185774
TI  - Personal view: randomized controlled trials in epilepsy specialist nursing: the
      seduction of content by form.
AB  - Research into the effectiveness of epilepsy specialist nursing needs to take into
      account a number of factors, which have not been adequately addressed in previous
      studies. Nursing outcome measures are different to medical ones and it is
      inappropriate to confuse these. Specialist nurses affect the whole culture of a
      service, and their impact on service quality may go beyond that of their
      individual patient contacts. Thus randomized studies within a service that
      already has specialist nurses may not give valid results. Some service users will
      benefit more from direct contact with a specialist nurse than others, and people
      who give informed consent to take part in randomized controlled trials might not
      be representative of those who would benefit most from specialist nurse access.
      The stampede for level one evidence risks failing to address the issues properly
      by overvaluing research process (form) against its appropriateness (content), yet
      there remain great opportunities for good quality research in this area.

PMID- 12185775
TI  - The cost of everything and the value of nothing: nursing case histories.
AB  - A series of three nursing case histories related to epilepsy care are presented
      to demonstrate the range of clinical nursing activity in an epilepsy clinic and
      to pose the question whether any of these activities, deemed essential by both
      clinician and nurse, would be thought appropriate if cost effectiveness of
      nursing care was merely measured by a significant reduction in seizure frequency.
      The conclusion drawn is that a specialist epilepsy nurse in an epilepsy clinic is
      an invaluable member of the team, who frees the medical member of the team to
      concentrate on those duties which need medical input: but, using currently
      applied outcome criteria, it would be difficult to justify the nurse's cost
      effectiveness. Measures that do this accurately and fairly must be developed.

PMID- 12185776
TI  - Continuing professional development: medico-legal aspects of epilepsy.
AB  - Generally protection against possible litigation and good clinical practice go
      hand in hand. Situations in which the law has special relevance for people with
      epilepsy, those who work with them, and their clinicians are reviewed with
      special reference to the topics of driving, employment, duties of social carers,
      the clinician's everyday role, the responsibilities of researchers and epilepsy
      and the criminal law. What constitutes professional negligence is discussed, with
      special reference to the United Kingdom. Clinicians are advised to think clearly,
      write clearly, communicate clearly and have a good relationship with their
      patients.

PMID- 12185778
TI  - [Brain-Net. The German Reference Center for diseases of the central nervous
      system].

PMID- 12185777
TI  - Epilepsy--doctor's dilemma, lawyer's delight? Medico-legal consequences of
      practising in the field of epilepsy report of an International League against
      Epilepsy British Branch meeting--Edinburgh, April 2000.
AB  - Six cases are described where the medical management of a person's epilepsy was
      brought under legal scrutiny. Lessons learnt from this educational exercise
      include improving doctor patient communication, the function of a Coroner's
      Court, when is misdiagnosis negligent, the vagaries of expert witnesses, should
      failure to diagnose a tumour be blamed on the physician or the service when
      facilities are inadequate, is failure to recognise a rare drug interaction,
      failure to warn against an interaction, or failure to take a proper history,
      negligent? The conference also examined the legal ramifications of the
      nurse/doctor relationship in epilepsy care, the place of epilepsy guidelines and,
      due to its interactive nature, reflected on the audience's epilepsy knowledge,
      which, in places seemed significantly deficient. It was a gripping educational
      exercise.

PMID- 12185779
TI  - [Creutzfeldt-Jakob disease. Lack or correlation between cerebral cortex histology
      and clinical course of the disease in 22 autopsy cases].
AB  - To detect a possible correlation between the neurology and duration of
      Creutzfeldt-Jakob disease (CJD) and cerebral pathology, we studied 22 autopsy
      cases by histological and immunohistochemical methods. The duration of disease
      ranged between 1 and 15 months with an average of 5.2 months. Only in 11 cases
      was the EEG typical for CJD. Morphologically the changes varied from minimal
      spongy changes to severe neuronal loss and brain atrophy. For the three cortical
      regions examined semiquantitatively, there was no correlation between the
      severity of spongiform changes and the duration of disease or the pattern of
      neurological symptoms. The study shows that more extensive sampling for the
      detection of regional heterogeneity of changes is mandatory in spongiform
      encephalopathies, and that complicating changes such as intermittent infections
      may play a role for the survival time as well. Moreover, genetic determinants,
      prion protein polymorphisms and the mode of exposure have to be considered as
      possible modulating factors.

PMID- 12185780
TI  - [The new WHO classification of tumors of the nervous system 2000. Pathology and
      genetics].
AB  - New developments in neuro-oncology have prompted an update of the World Health
      Organization (WHO) classification of tumors of the nervous system. Major changes
      include the addition of new entities and the refinement of criteria for the
      diagnosis and grading of various neoplasms, in particular the meningiomas. As
      novel clinico-pathological entities, the chordoid glioma of the third ventricle,
      the atypical teratoid/rhabdoid tumor (AT/RT), the solitary fibrous tumor, and the
      perineurioma have been listed. The former lipomatous medulloblastoma of the
      cerebellum, previously incorporated in the family of embryonal tumors, is now
      classified as cerebellar liponeurocytoma. The term mixed
      pineocytoma/pineoblastoma has been replaced by pineal parenchymal tumor of
      intermediate differentiation. Furthermore, the large cell medulloblastoma and the
      tanycytic ependymoma were established as novel tumor variants. A separate chapter
      on the peripheral neuroblastic tumors has now been included in the
      classification. Substantial revisions were introduced in the meningioma chapter.
      For both atypical meningioma WHO grade II and anaplastic meningioma WHO grade
      III, histopathological criteria are now precisely defined. An important new
      addition to the WHO 2000 classification of nervous system tumors is the inclusion
      of molecular pathology findings. With this combination of pathology and genetics
      it has set the stage for a new format of the WHO tumor classification series.

PMID- 12185781
TI  - [Primary CNS lymphomas. Morphology and diagnosis].
AB  - Diagnostically primary central nervous system lymphomas (PCNSL) have to be
      differentiated from glioblastoma and brain metastases. Histologically the
      overwhelming majority of PCNSL is represented by diffuse large B-cell lymphomas,
      in this series with a BCL6 expression in 80% of the cases detected by
      immunohistochemistry. Stereotactic biopsy is the method of choice in establishing
      the definite diagnosis and intraoperative smear cytology will detect the lymphoid
      blasts. To confirm the B-cell lineage, immunohistochemistry is needed (CD20,
      CD79a). Small reactive T-lymphocytes and monohistiocytic cells and activated
      "microglia" are found within and at the periphery of PCNSL foci. The infiltrated
      brain tissue shows partially pleomorphic reactive astrocytes that can be confused
      with neoplastic astrocytes, especially in small specimens. In contrast to high
      grade gliomas, however, PCNSLs do not show endothelial proliferations. Subtypes
      or variants of diffuse large B-cell lymphomas can also be observed in cases of
      PCNSL: the anaplastic variant with large multinucleated tumour cells resembling
      Reed-Sternberg cells, T-cell rich B-cell lymphoma and intravascular B-cell
      lymphoma with primary manifestation within the brain or the spinal cord. HIV/AIDS
      associated PCNSLs are characterised by large plasmoblastic or small Burkitt-like
      cells and tumour necrosis. Primary leptomeningeal large B-cell lymphomas do occur
      very rarely and are diagnosed by cerebrospinal fluid cytology.

PMID- 12185782
TI  - [Diagnostic value of the monoclonal antibody to thyroid transcription factor 
      1(TTF-1) in CNS metastases. An immunohistochemical study of 65 cases].
AB  - Thyroid transcription factor-1 (TTF-1) is used as an immunohistochemical marker
      for the identification of the lungs or thyroid gland as the site of origin in
      patients with metastatic disease and unknown primary tumor. In this study the
      reliability of anti-TTF-1 was assessed in 65 metastases of the central nervous
      system (CNS), among which there were also small stereotactic biopsies (n = 22)
      and poorly preserved specimens. Eight out of nine CNS metastases of patients with
      known adenocarcinoma of the lungs, as well as seven adenocarcinoma metastases of
      patients with radiologically detected or anamnestically presumed pulmonary
      carcinoma, expressed TTF-1 immunohistochemically. One CNS metastasis from a
      follicular thyroid carcinoma was positive and one from an anaplastic thyroid
      carcinoma was negative. All CNS metastases from patients with known primary
      tumors outside the lungs or thyroid gland were negative. TTF-1 is a sensitive (up
      to 90%) and specific (100%) immunohistochemical marker for CNS metastases of
      adenocarcinomas of the lungs and also functions reliably on small or stereotactic
      biopsies and poorly preserved samples.

PMID- 12185783
TI  - [Rhabdoid meningioma. A new malignant subtype].
AB  - Of the numerous morphological variants of meningiomas only few, and among these
      the rhabdoid meningioma, have prognostic importance. Rhabdoid meningiomas were
      described for the first time in 1998 as an unusual variant with increased
      proliferative activity. In 2000 they have been included in the revised WHO
      classification of tumours of the CNS as a subtype of meningiomas with increased
      risk of recurrence and more aggressive growth, corresponding to WHO grade III. We
      report the case of a rhabdoid meningioma in a 21-year-old woman presenting as a
      intracerebral tumour mimicking an oligodendroglioma. The tumour showed features
      of a meningioma and a rhabdoid morphology with angiomatous components and was
      considered to be a rhabdoid meningioma. After surgery a small residual tumour
      remained. The patient received postoperative radiotherapy resulting in regression
      of the residual tumour in control examinations after 4 and 8 months. Using the
      presented case we discuss the differential diagnosis and prognostic significance
      of recognition of a rhabdoid meningioma.

PMID- 12185784
TI  - [Differentiated papillary kidney tumors. Differentiation between metanephric
      adenoma and papillary adenoma].
AB  - Metanephric adenoma of the kidney is a well described tumor entity. The
      differential diagnosis between papillary adenoma or papillary carcinoma type 1
      and metanephric adenoma of the kidney can be challenging in single cases. We
      report two cases of metanephric adenomas and compare their immunophenotype with a
      papillary adenoma. The analysis of these metanephric adenomas and a review of the
      literature shows that CD-57 positivity and lack of EMA expression are helpful in
      distinguishing metanephric adenoma from papillary adenoma and papillary
      carcinoma. Glomeruloid structures, Psammoma bodies, necrosis or expression of
      cytokeratin 7 and vimentin are common features in metanephric adenoma and
      papillary adenoma or papillary carcinoma. The knowledge of the
      immunohistochemical constellation is important, because metanephric adenoma can
      be very large and often have some necrosis.

PMID- 12185785
TI  - [Merkel cell carcinoma after kidney transplantation. Extreme living conditions as
      an indirect cause of death].

PMID- 12185787
TI  - [Extensive bilateral lower leg muscle necrosis after nasal application of heroin.
      Macroscopic and histologic findings in a 23-year-old man].
AB  - Rhabdomyolysis is one of the less known complications of heroin abuse. A case of
      lower leg muscle necrosis after nasal application of heroin is reported with
      repeated resection of the necrotic muscles. Superinfection with a methicillin
      resistant Staphylococcus aureus (MRSA) strain was present. After 4 weeks,
      bilateral amputation could not be avoided. We regard a direct toxic effect of the
      heroin as the most probable mechanism of the muscular damage, with possible
      influence of the reduced oxygen delivery due to central respiratory and
      circulatory depression.

PMID- 12185786
TI  - [Carcinoma cuniculatum of the oral cavity. A contribution to the differential
      diagnosis of potentially malignant papillary lesions of mouth mucosa].
AB  - Although carcinoma cuniculatum clinically appears to be malignant, histological
      evaluation often results in a false diagnosis of a benign papillomatous lesion or
      pseudoepitheliomatous hyperplasia, because the tumor usually displays a well
      differentiated tissue. In this report morphological and immunohistological
      features in a rare case of carcinoma cuniculatum of the oral cavity are
      described. Both clinical features and histomorphological evaluation must be taken
      into consideration when diagnosing the tumor.

PMID- 12185788
TI  - Evaluation of a worksite smoking-cessation program.

PMID- 12185789
TI  - Longer distal motor latency predicts better outcomes of carpal tunnel release.

PMID- 12185790
TI  - Human pulmonary disease and exposure to Stachybotrys chartarum and other
      toxigenic fungi.

PMID- 12185791
TI  - Agreement between prospective and retrospective reports of maternal exposure to
      chemicals during pregnancy.
AB  - As part of a prospective study of solvent exposure and child behavior, it
      occurred that women's responses about exposure history during pregnancy differed
      from the information documented during the postpartum period. The objective of
      the study was to examine the levels of agreement in 29 self-reports of exposure
      information obtained before and 3- to 7-years after pregnancy. Percent agreement
      was low for duration of exposure (41%), protective barrier use (48%), and
      symptomatology (41%). When reports were not in perfect agreement, women tended to
      report longer durations of exposure (r = 0.67), increased use of protective
      barriers (r = 0.39), and more symptoms at time of follow-up (r = 0.57). Agreement
      of report was not substantially associated with time since pregnancy or
      concurrent child behavior. Low levels of agreement may reflect response biases in
      the data collected at time of pregnancy or recall biases at time of follow-up.
      These variations in self-reports are of concern because they can severely affect
      estimates of human teratological risk.

PMID- 12185792
TI  - Hazardous substances emergency events in the agriculture industry and related
      services in four mid-western states.
AB  - Analysis of Hazardous Substances Emergency Events Surveillance data reported from
      14 participating states between 1993 and 1998 found that acute releases are
      seasonal. This seasonality was more prevalent in four Midwestern states during
      April-June and coincided with their planting season, suggesting an association of
      these releases with the agricultural industry. A more detailed analysis of events
      related to this industry in these states found that ammonia was the chemical most
      frequently released, and ammonia related events resulted in a significantly
      higher number of evacuations than all other events (OR = 10.7, [5.25-22.28]). A
      logistic regression model to identify risk factors for an event with victims
      found an increased risk for: (1) events with ammonia during April-June (adjusted
      OR = 3.57, [2.09-6.09]); (2) events in fixed-facilities during April-June (aOR =
      3.74, [2.01-6.95]); and (3) events with multiple substances (aOR = 2.33, [1.05
      5.17]). The most common causes for the events were equipment failure and operator
      error. Resulting injuries were mainly respiratory, ocular and traumatic, and
      included six deaths. Employing more stringent safety measures and educating
      employees and the public about the health hazards involved with agricultural
      chemicals may reduce injuries and help contain costs associated with the
      releases.

PMID- 12185793
TI  - Validity of a self-administered questionnaire for assessing physical work loads
      in a general population.
AB  - The aim of the study was to evaluate eight questions concerning physical loads,
      used in public health questionnaires. Working women and men (203) completed a
      self-administered questionnaire twice, following a test-retest method. The
      questions were also validated with a structured interview. Response agreement was
      calculated with Cohen's kappa statistics with quadratic weights (kappa w). Test
      retest agreement varied from 0.74 to 0.92, and inter-method agreement from 0.38
      to 0.81. The lowest coefficients were for the questions concerning bent/twisted
      work postures (kappa w 0.38) and repetitive movements (kappa w 0.39). The results
      did not indicate any substantial influence of gender, type of work or
      musculoskeletal complaint. The questions concerning general physical activity and
      sitting work postures, and physical exercise/sports during leisure times, had
      good validity. The questions concerning bent/twisted work posture and repetitive
      movements need to be re-designed.

PMID- 12185794
TI  - The value of the periodic executive health examination: experience at Bank One
      and summary of the literature.
AB  - The executive physical examination has been advocated in the United States for
      almost 100 years. A MEDLINE search of the literature found very few studies that
      document the potential impact of a worksite physical examination program on
      medical and disability costs. Bank One has performed executive physical
      examinations at its corporate headquarters' medical department since 1983.
      Approximately 65% of eligible executives voluntarily participate in the program
      annually. Medical claims and short term disability data were available for a
      total of 1773 executives who were eligible for a physical examination for a
      consecutive 3-year period. For three consecutive years after the initial physical
      examination, the Bank paid a total of $5361 for medical claims for periodic
      health examination participants (PHE) in contrast to $6426 paid for medical
      claims for non-periodic health examination participants (NPHE). PHE participants
      experienced an average 0.93 (or 2.78 for 3 years) short-term disability days
      absent per year in comparison with an average of 1.34 (or 4.02 for 3 years) short
      term disability days absent for NPHE. The net return on investment for a worksite
      based executive health examination which cost approximately $400 per executive
      whose total compensation (salary and benefits) is at least $125,000 is estimated
      to be 2.3:1, which compares favorably with other preventive health programs.

PMID- 12185795
TI  - Hemochromatosis detection in a health screening program at an Alabama forest
      products mill.
AB  - We analyzed hemochromatosis detection in a 11.5-year multiphasic health screening
      program at a forest products mill. There were 2199 participants: 2032 Whites
      (1506 men, 526 women) and 167 African Americans (124 men, 43 women); 85.0% of
      employees were screened. Iron and transferrin saturation were measured in a serum
      biochemistry profile on specimens obtained after overnight fasting; ferritin was
      measured in participants with elevated iron concentrations or transferrin
      saturation > 48%. Participants with elevated ferritin levels underwent further
      evaluation. Eight White men were diagnosed to have hemochromatosis (frequency
      0.0039 in Whites, 0.0053 in White men). The estimated cost per case detected was
      $8826. Family members of two participants with hemochromatosis were also
      diagnosed to have hemochromatosis or iron overload. We conclude that detecting
      hemochromatosis in a workplace multiphasic health screening program is
      efficacious and economical.

PMID- 12185796
TI  - Incidence of asthma among Finnish construction workers.
AB  - We wanted to explore the risk of asthma among male workers of the construction
      industry. All Finnish male construction industry workers and all those employed
      in administrative work were followed for asthma incidence through a register
      linkage in 1986 through 1998. Age-adjusted relative risks (RR) were estimated for
      24 construction occupations. The risk was increased in nearly all construction
      occupations studied, but it was highest among welders and flame cutters (RR
      2.34), asphalt roofing workers (RR 2.04), plumbers (RR 1.90), and brick layers
      and tile setters (RR 1.83). Only 45 (2%) of the cases of asthma among
      construction workers had been recognized as occupational asthma. Construction
      industry workers have an increased risk of adult-onset persistent asthma and
      cases of occupational asthma caused by well-established causative agents have
      only a minor contribution to this overall asthma excess.

PMID- 12185798
TI  - Relationship between amyloid beta protein and melatonin metabolite in a study of
      electric utility workers.
AB  - This study assessed the relationship between occupational magnetic field
      exposure, the urinary melatonin metabolite 6-hydroxymelatonin sulfate (6-OHMS),
      and concentrations of blood-borne soluble amyloid beta (A beta), a protein
      associated with the hallmark lesions of Alzheimer's disease (AD). Blood and urine
      samples were obtained from male electric utility workers (n = 60) to quantify two
      lengths of the protein in plasma, A beta (amino acids 1-40) and A beta (1-42),
      and the urinary concentrations of 6-OHMS. Average A beta levels were positively
      associated with categories of magnetic field exposure, but this relationship was
      weak and did not achieve statistical significance. The melatonin metabolite was
      inversely correlated with A beta (1-42) and the ratio of A beta (1-42) to A beta
      (1-40). This observation is consistent with recent in vitro data and provides a
      plausible mechanism for the association between magnetic field exposure and AD
      that has been observed in some studies.

PMID- 12185797
TI  - Ten years and 100,000 participants later: occupational and other factors
      influencing participation in US Gulf War health registries.
AB  - For more than a decade after the Gulf War, there has been concern that wartime
      exposures have resulted in significant morbidity among Gulf War veterans. After
      the end of the war, the Department of Veterans Affairs (VA) and the Department of
      Defense (DoD) initiated health registries to provide systematic clinical
      evaluations of Gulf War veterans who chose to participate. By September 1999,
      there were 32,876 participants in the DoD Comprehensive Clinical Evaluation
      Program and 70,385 participants in the VA Gulf War Registry Health Examination
      Program. We identified demographic and military service factors, as well as
      potential war-related exposures associated with subsequent registry participation
      after 10 years of observation. Veterans potentially exposed to oil well fire
      smoke, those near Khamisiyah, Reserve and National Guard, Army veterans, and
      veterans in the theater of operations during intense combat periods were most
      likely to elect to participate in a registry. These findings support the
      hypothesis that certain occupational factors and wartime exposures may influence
      subsequent health care-seeking behavior.

PMID- 12185799
TI  - Influence of participation in a worksite health-promotion program on disability
      days.
AB  - This study assessed the impact of health-promotion program participation on short
      term and long-term disability absence days during a 6-year period in a
      manufacturing company. Male, hourly, active employees (n = 4189) were analyzed
      from 1995 to 2000. Disability absences were compared for program participants and
      nonparticipants from baseline (1995) through 5 years of the program. The
      percentage of nonparticipants absent on any given day was greater than that of
      participants. Moreover, the average number of disability absence days incurred by
      nonparticipants significantly increased from baseline to program year 5 compared
      with participants. The total amount saved each year in disability absence days
      for the 2596 program participants was $623,040, which resulted in a savings-to
      cost ratio of 2.3 per year. Participation in worksite health-promotion programs
      may lead to reduced disability days in a manufacturing worksite population.

PMID- 12185800
TI  - [Nobel Prize in Physiology and Medicine 2001].

PMID- 12185801
TI  - [Swallowing disorders in Parkinson's disease].
AB  - Impairment of swallowing is a common symptom in advanced stage of Parkinson's
      disease and severe defect of this function may cause aspiration pneumonia,
      problems with food intake and cachexy. The aim of this study was to assess the
      reflex and oral, pharyngeal, oesophageal phase of swallowing. Eleven patients
      with Parkinson's disease and 9 healthy subjects were investigated by
      electromyography (EMG) and oesophageal scintigraphy. The study demonstrates
      delayed triggering of swallowing reflex (543 +/- 84 ms in patients with PD vs.
      230 +/- 66 ms in controls, p < 0.05) and prolongation of laryngeal movement (1880
      +/- 140 ms vs. 1349 +/- 154 ms, p < 0.05). The prolongation of the oesophageal
      phase of swallowing with predilection to retention of water in lower one/third
      part of esophagus (12.45 +/- 2.45 s vs. 6.45 +/- 1.18 s, p < 0.001) was observed.
      The dysphagia limit, that is the maximum amount of water swallowed at once, was
      also evaluated (all normal subjects are able to swallow 20 ml water or more at
      once). In the studied patients with Parkinson's disease it was 4.5 +/- 0.86 ml.
      These results evidently and objectively indicate the presence of swallowing
      disorders in Parkinson's disease. Dysphagia was observed in all studied patients,
      although only 8 of them complained about it. In other 3 cases the impairment of
      swallowing was subclinical and it was connected with prolongation of oesophageal
      phase.

PMID- 12185803
TI  - [Sixteen-year experience in the treatment of trigeminal neuralgia by percutaneous
      retrogasserian thermorhizotomy].
AB  - The authors present a series of 143 consecutive patients with trigeminal
      neuralgia who were treated with percutaneous retrogasserian thermorhizotomy
      between 1984 and 2000. Long time results (follow-up of 16 years) revealed full
      pain relief in 80% of patients, mainly in those with postoperative sensory
      deficit, 16% suffered pain recurrence and required additional treatment.

PMID- 12185802
TI  - [MELAS--mitochondrial encephalomyopathy with lactic acidosis and stroke-like
      episodes syndrome--two cases confirmed by biochemical and molecular
      investigations. Differential diagnosis of stroke causes].
AB  - Mitochondrial encephalomyopathy, lactic acidosis and stroke-like episodes
      syndrome (MELAS) is a maternally inherited multisystem disease caused by
      mutations of the mitochondrial DNA. The characteristic clinical features are:
      encephalopathy manifesting as dementia and seizures, stroke-like episodes at
      young age (usually < 40), lactic acidosis and myopathy with ragged-red fibres.
      Other frequent manifestations include: sensorineural deafness, diabetes,
      hypoparathyroidism, peripheral neuropathy and cardiomyopathy. We present two
      patients with MELAS who were diagnosed 4 and 9 years respectively following the
      onset of the disease despite the characteristic clinical pictures. The
      differential diagnostics of inborn and acquired disorders causing stroke is
      included. We regard that mitochondrial diseases are still insufficiently known
      and are frequently misdiagnosed. The knowledge is indispensable for establishing
      diagnosis and accurate genetic counselling. Although there is no specific therapy
      for mitochondrial diseases to date, coenzyme Q and various vitamins as well as
      moderate degree exercise might be recommended.

PMID- 12185804
TI  - [Difficulties in stereotactic biopsies of brain tumors].
AB  - MATERIAL: 28 stereotactic biopsies of organic brain processes (brain tumours)
      were performed in the years 1997-2000 in the Department of Neurosurgery, Medical
      University of Warsaw. In this series the lesions were located in corpus callosum
      in 5 patients, in basal nuclei in 9, and deeply in the white matter of cerebral
      hemispheres in 14. METHOD: The Baklund biopsy kit and Leksell's stereotactic
      frame were used, target localisation was based on the CT scan. Histological
      verification was based on hematoxillin--eosin staining, completed with
      histochemical evaluation if necessary. In 9 patients intraoperative smear
      evaluation was performed. RESULTS: Sensitivity of stereotactic biopsies was 86%
      (24/28), although the rate of conclusive biopsies was lower, being 60% (17/28).
      False negative results were observed in 14% of the patients (4/28). Analysis of
      the results revealed, that the sensitivity was not dependent on the size, neither
      on the location of the tumour, but was related to its morphology. The false
      negative results were obtained in the tumours with significant necrosis (as seen
      on CT scans). There were no surgical complications in this series. CONCLUSIONS:
      1. Difficulties in stereotactic biopsies of brain tumours are associated mainly
      with tumour morphology. In tumours with marked necrosis, other degenerative
      changes or cystic ones, higher risk of non-conclusive biopsy may be expected. 2.
      Size of the tumour and its location do not affect the diagnosis based on the
      stereotactic biopsies. 3. In the polymorphic tumours, the policy to take biopsy
      material from different tumour sites, should be a rule, as different parts of the
      lesion may represent different stages of malignancy and histological evaluation
      of separate parts of the tumour may lead to inadequate oncological treatment.

PMID- 12185805
TI  - [Chlamydia pneumoniae infection and multiple sclerosis].
AB  - Possible association of Chlamydia pneumoniae and multiple sclerosis is the
      subject of recent interest. The findings concerning the isolation of the agent
      from CSF and tissue from postmortem brain are controversial, similarly as
      absorption of oligoclonal bands in CSF by this antigen. The hypothesis should be
      further studied to establish whether an association of Ch. pneumoniae with MS
      exists or not.

PMID- 12185806
TI  - [Tic syndrome].
AB  - A tic is an involuntary, sudden, rapid, recurrent, nonrrhythmic, stereotyped,
      motor movement or vocalization. This paper reviews clinical, pathophysiological,
      epidemiological and treatment issues of tic disorders. The clinical presentation
      of tic disorders with simple and complex motor or vocal tics is reviewed in
      detail. The most common psychiatric comorbid conditions, such as personality
      disorder (PD), Obsessive-Compulsive Disorder (OCD), Self-Destructive Behavior
      (SDB) and Attention Deficit Hyperactivity Disorder (ADHD) are presented too. All
      forms of tics may be exacerbated by anger or stress, but they are usually
      markedly diminished during sleep. Premonitory feelings or "sensory experiences",
      which are distinct from the actual motor or phonic tics and precede the tics,
      occur in over 80% of tic-patients and in 95% of patients with Gilles de la
      Tourette Syndrome (GTS). The American Psychiatric Association recognizes three
      types of tic disorders on the basis of clinical criteria: Transient Tic Disorder,
      Chronic Motor or Vocal Tic Disorder and GTS. The diagnostic criteria for these
      types are described. According to epidemiological data, up to 10% of children
      have at least somewhere a transient tic disorder. The onset of tics, whether
      simple or multiple, occurs at approximately 7 years of age. The accepted
      prevalence figure for GTS is 0.05-3%. Although tics can appear as the result of
      brain injury, Huntington chorea or encephalitis, they are most commonly
      idiopathic. Genetic factors appear to be present in many but not in all cases of
      tic disorders. Autosomal dominant, sex-linked models or semirecessive
      semidominant-oligogenic models have been considered. Based on the review of the
      literature we believe that tic disorders are related to altered neurotransmitter
      function within the CNS, especially that the functional abnormality is somehow
      related to dopaminergic mechanism. Several authors have recently investigated the
      possible role of autoimmune response to streptococcal infection in the
      pathogenesis of tics. The differential diagnosis of tics is reviewed in detail.
      Above all tics represent a social disability. The ability to tolerate tics varies
      greatly from one individual to another, and the need for treatment is better
      defined by the patient than by the physician. Mild cases do not need be treated.
      Ideally, management should be multidisciplinary and can range from educative to
      supportive means or to intricate pharmacological interventions. The major form of
      treatment of the motor or vocal symptoms continues to be based on high-potency
      "typical" neuroleptics (tiaprid, pimozide, haloperidol), which induce a wide
      range of potentially serious side effects. In everyday practice we prefer to
      start with an "atypical" neuroleptic drug--for example, olanzapin (5-10 mg/day),
      risperidone or clozapine. Other drugs, such as clonidin or pergolid are widely
      used but their efficiency is still questionable. SSRIs (sertaline, citalopram,
      fluoxetin, fluvoxamine) or other antidepressants (clomipramine) have been used in
      treatment of psychiatric comorbid conditions, too. Botulinum toxin injections
      have proved useful in tics, targeting at the symptoms of blepharospasm, in neck
      and facial muscles.

PMID- 12185807
TI  - [Axonal damage in multiple sclerosis].
AB  - Traditionally, it was believed in MS, that axonal loss occurred in chronic
      lesions. However, new findings suggest that axonal transection can begin very
      early in the course of multiple sclerosis and axonal damage was found in active
      and chronic active MS lesions, particularly in areas of acute inflammation and
      demyelination. The mechanisms of axonal loss are uncertain, but may involve
      axonal degeneration secondary to demyelination, the action of inflammatory
      mediators and immune attack directed at axonal components. Axonal destruction and
      it's progression, is the major cause of irreversible damage in the CNS and the
      increase of disability in MS patients. Currently, new diagnostic methods (MRI, MR
      spectroscopy, magnetic transfer, histopathological and biochemical study) allow
      better to know the mechanisms of neuronal damage.

PMID- 12185808
TI  - [Molecular and genetic basis of idiopathic nocturnal frontal lobe epilepsy].
AB  - In this review current literature on autosomal dominant nocturnal frontal lobe
      epilepsy (ADNFLE) is presented and discussed. This disease is caused by mutations
      of genes coding for sub-units of neuronal acetylcholine receptor comprising
      sodium/potassium ion channel. To date, three types of mutations of the gene
      encoding alpha 4 sub-unit of acetylcholine receptor were described in
      multigeneration families in Australia, Spain, Norway and Japan, as well as two
      types of mutations of the beta 2 sub-unit in two families, one from Italy and the
      other from Scotland. Mutations were caused by substitutions of a single
      nucleotide or several nucleotide insertions and resulted in lowering of the
      activity of the receptor or changes in the affinity to the ligand. Recent
      advances in molecular genetics have provided the means for better understanding
      of human epileptogenesis at molecular level, which facilitates clinical
      diagnosis, provides more rational basis of therapy and prevention of this form of
      epilepsy.

PMID- 12185809
TI  - [Neuropsychological rehabilitation of patients with disorders of the so called
      executive functions caused by prefrontal brain lesions].
AB  - The prefrontal brain injury may impair several cognitive and emotional functions.
      In our article we present typical features of these impairments. The current
      studies present a different therapeutic approach to the dysexecutive syndrome.

PMID- 12185810
TI  - [Surgical methods of spasticity treatment].
AB  - This article presents the topical views on the surgical treatment of spasticity.
      On the ground of available literature the authors tried to present the
      indications for different surgical procedures according to a etiology and
      different parts of the body and the groups of the muscles afflicted of
      spasticity.

PMID- 12185811
TI  - [The molecular basis of glia-derived tumours of the brain. Part I].
AB  - The development and progression of astrocytic tumours is associated with
      acquisition and accumulation of genetic alternations. Loss of heterozygosity
      (LOH) on chromosome 17p., p53 mutations and overexpression of the platelet
      derived growth factor (PDGF) receptor (chromosome 22q), are the most common
      detectable changes in astrocytomas (WHO grade II). Anaplastic astrocytomas (WHO
      grade III) involve LOH on chromosome 19q, deletion of p16 tumor suppressor gene
      on chromosome 9p and disturbed expression of gene RB on chromosome 13q. LOH on
      chromosome 10 is restricted largely to glioblastomas (WHO grade IV). This tumour
      also is characterized by amplification and/or overexpression of gene coding
      Epidermal Growth Factor Receptor (EGFR) on chromosome 7p. There is growing
      evidence that two genes encoding triiodothyronine receptors TR alpha [17q21] and
      TR beta [3p21-p25]) belong also to the group of genes involved in tumorigenesis.
      Mutations of these genes as well as markedly disturbed expression and function of
      the encoded proteins were found in tumour tissue. This is supported by facts.
      that T3 via TRs regulate proliferation, growth, differentiation and apoptosis,
      the processes that are deeply disturbed in tumour tissue. TRs affects also the
      action of certain protooncogenes (Mdm2) and tumor suppressors (p53, Rb).

PMID- 12185812
TI  - [Antemortem diagnosis of Balo's concentric sclerosis based on MRI. Case report].
AB  - Balo's concentric sclerosis is a rare variant of multiple sclerosis. It is
      pathologically characterized by alternating rings of demyelination and spared
      myelin. Recently, MRI was applied to demonstrate characteristic patterns in this
      disease. We report a case of Balo's concentric sclerosis diagnosed by the typical
      MRI findings of concentric rings of demyelination.

PMID- 12185813
TI  - [Leptomeningitis carcinomatosa with progressive involvement of the cranial nerves
      -report of two cases].
AB  - This paper reports two cases of leptomeningitis carcinomatosa with progressive
      cranial nerves injury as the first clinical sign of disseminated disease.
      Neurological state, diagnostic procedure and treatment are described.

PMID- 12185814
TI  - [Surgical treatment of trigeminal neurinoma].
AB  - The article presents the group of five patients with clinical and radiological
      symptoms of trigeminal neurinoma that were operated on in the Neurosurgical
      Clinic of Central Clinical Hospital of Military Medical Academy in the five-years
      period (1995-2000). Three of them were operated in a single step procedure from
      subtemporal and suboccipital approach. Two other were operated in two steps, also
      from subtemporal and suboccipital approaches. Four neurinomas were removed
      radically, as confirmed by CT, and MRI scans. All the patients are independent
      and professionally active. Complications observed after the operation were:
      persistent anaesthesia in the trigeminal area, atrophy of the masseter muscle,
      transient paresis of the facial nerve with ulceration and opacification of the
      cornea, and transient paresis of the abducens nerve.

PMID- 12185815
TI  - [Is there a restless arms syndrome?].
AB  - Three patients are reported who had painful numbness in upper extremities
      regressing temporarily after performing rather intensive movements. Analgesics
      are non efficacious in relieving this symptom. The observed painful syndrome
      relieved for some time by movements of the upper extremities seems to be an
      analogy of the restless legs syndrome. Perhaps the designation "restless arms
      syndrome" could be introduced.

PMID- 12185816
TI  - [Report from the 2nd Central European Workshop on Microvascular Neurosurgery.
      Ceskie Budejovice, Czech Republic, 15-16 November, 2001].

PMID- 12185817
TI  - [Report from the Symposium "Catholic Volunteers in Health Service."].

PMID- 12185818
TI  - [Report on the 5th International Neurotrauma Symposium INTS 2000. Garmisch
      Partenkirchen, Germany, October 1-5, 2000].

PMID- 12185820
TI  - Medical malpractice insurance--is a crisis brewing?

PMID- 12185819
TI  - Medicare in the spotlight.

PMID- 12185822
TI  - Fighting the good fight.

PMID- 12185821
TI  - Mandatory abuse training--new developments for an old law!

PMID- 12185823
TI  - Drug information leaflets for consumers need improvement, FDA says.

PMID- 12185824
TI  - Pharmacists and the treatment of depression.

PMID- 12185825
TI  - Harvey A. K. Whitney lecture. Prescription for safety in health care.

PMID- 12185826
TI  - Impact of a collaborative pharmacy practice model on the treatment of depression
      in primary care.
AB  - The effects of a collaborative pharmacy practice model, in which clinical
      pharmacy specialists provided medication maintenance and follow-up patient care
      services at a clinic, on patients' adherence to treatment and satisfaction and
      costs were studied. A cohort of 13 primary care providers (PCPs) was designated
      to refer patients diagnosed with depression to the practice model at a staff
      model health maintenance organization (HMO) immediately after the initiation of
      antidepressant medications. Clinical pharmacy specialists proceeded to coordinate
      follow-up with the patients for six months through a combination of scheduled
      office visits and telephone calls. Working closely with psychiatric liaisons,
      pharmacists were granted limited prescribing privileges to provide medication
      comanagement. These patients' adherence to treatment and satisfaction and costs
      to the HMO were compared with a control group of patients being treated for
      depression by the remaining 17 PCPs at the facility. A total of 91 patients were
      referred to the intervention group and received care from the pharmacists during
      the 10-month enrollment phase; 129 patients were included in the control group.
      There were no significant differences between groups regarding age, sex and
      chronic disease scores. An intent-to-treat analysis of medication adherence
      revealed that adherence was significantly higher in the intervention group
      (medication possession ratio, 0.81 versus 0.66) (p = 0.0005). Medication switch
      rates were higher among intervention patients as well (24% versus 5%) (p =
      0.0001). There was a greater decline in the number of visits to PCPs for patients
      in the intervention group (39% versus 12%) (p = 0.029). A collaborative practice
      model in which clinical pharmacy specialists managed the medication therapy of
      patients with mild to moderate depression increased patients' adherence to
      treatment and their satisfaction and reduced the patients' subsequent visits to
      PCPs.

PMID- 12185827
TI  - Variations in parthenolide content and daily dose of feverfew products.
AB  - Variations in the parthenolide content of feverfew products available to
      consumers were studied. Feverfew products were analyzed for the content of
      parthenolide, the purported active component. The actual weight of feverfew was
      determined only in those products containing dried feverfew leaf. The total daily
      doses of feverfew leaf and parthenolide were calculated by using the instructions
      on each product label. Parthenolide content was determined by high-performance
      liquid chromatography. The quantity of feverfew leaf in each capsule was similar
      to that stated on the label and ranged from 25 to 500 mg. Parthenolide content
      per dosage form varied 150-fold (from 0.02 to 3.0 mg), while percent parthenolide
      varied 5.3-fold (from 0.14% to 0.74%). If a person consumed the daily dose
      recommended on the label, intake of dried feverfew leaf would range from 225 to
      2246 mg/day, a 10-fold variation, while intake of parthenolide would range from
      0.06 to 9.7 mg/day, a 160-fold variation. Large variations were observed in the
      parthenolide contents and daily intake as recommended by the labeling in
      commercial feverfew products.

PMID- 12185828
TI  - Simple intravenous antimicrobial desensitization method for pediatric patients.

PMID- 12185829
TI  - Stability of cefazolin in heparinized and nonheparinized peritoneal dialysis
      solutions.

PMID- 12185831
TI  - A passion for practice: recentering the social mission of pharmacy.

PMID- 12185830
TI  - Educational program to reduce major bleeding in patients undergoing percutaneous
      coronary interventions and receiving abciximab.

PMID- 12185832
TI  - The new realities of practice in a post-9/11 world.

PMID- 12185833
TI  - Patient perceptions about drug advertising and prescription-to-nonprescription
      switches.

PMID- 12185834
TI  - Contacting patients of a Pakistani hospital about a drug recall.

PMID- 12185835
TI  - Drug safety and effectiveness in children.

PMID- 12185836
TI  - Mutations in the Lcb2p subunit of serine palmitoyltransferase eliminate the
      requirement for the TSC3 gene in Saccharomyces cerevisiae.
AB  - Serine palmitoyltransferase catalyses the committed step in sphingolipid
      synthesis, the condensation of serine with palmitoyl-CoA to form 3
      ketosphinganine. Two proteins, Lcb1p and Lcb2p, are essential for enzyme activity
      and a third protein, the 80-amino acid Tsc3p, stimulates the activity of serine
      palmitoyltransferase several-fold. Tsc3p physically associates with a complex of
      Lcb1p-Lcb2p and stimulates enzyme activity posttranslationally, but its precise
      function is not known. Tsc3p is essential for cell viability only at elevated
      temperatures, although serine palmitoyltransferase activity is reduced in the
      tsc3 delta mutant, even at permissive growth temperatures. Tsc3p is apparently
      not required for any essential process besides stimulation of serine
      palmitoyltransferase at 37 degrees C, since providing sphingoid bases to the
      growth medium reverses the temperature-sensitive growth phenotype of the tsc3
      delta mutant. To gain further insight into the function of Tsc3p, suppressor
      mutants that eliminate the Tsc3p requirement for growth at 37 degrees C were
      isolated and characterized. These studies show that dominant mutations in the
      Lcb2p subunit of serine palmitoyltransferase suppress the temperature-sensitive
      growth phenotype of the tsc3 delta null mutant by increasing the Tsc3p
      independent serine palmitoyltransferase activity.

PMID- 12185838
TI  - Identification of a Candida glabrata homologue of the S. cerevisiae VRG4 gene,
      encoding the Golgi GDP-mannose transporter.
AB  - Mannoproteins on the cell wall of yeast and fungi help regulate cell shape,
      porosity, and cell-cell interactions, including those required for attachment to
      host cells by fungal pathogens. The mannose-containing oligosaccharides on
      proteins and lipids are extended in the Golgi by glycosyltransferases that use
      GDP-mannose as the sugar substrate. A membrane-bound transporter that, in
      Saccharomyces cerevisiae, is encoded by the VRG4 gene catalyses delivery of GDP
      mannose into the lumen of the Golgi. We report here the cloning of the homologous
      VRG4 gene from the pathogenic yeast, Candida glabrata, by functional
      complementation of an S. cerevisiae vrg4 mutant. The sequence of the CgVrg4
      protein displays significant homology to GDP-mannose transporters from other
      yeast, fungi, protozoa, and plants. CgVRG4 fully complements the glycosylation
      defect and other cell wall associated vrg4 mutant phenotypes. Like ScVRG4, CgVRG4
      is essential for the viability of C. glabrata. These results suggest that, as in
      S. cerevisiae, CgVrg4p accounts for all of the GDP-mannose transport activity in
      the Golgi lumen.

PMID- 12185837
TI  - Mutations in Fks1p affect the cell wall content of beta-1,3- and beta-1,6-glucan
      in Saccharomyces cerevisiae.
AB  - Fks1p and Fks2p are related proteins thought to be catalytic subunits of the beta
      1,3-glucan synthase. Analysis of fks1 delta mutants showed a partial K1 killer
      toxin-resistant phenotype and a 30% reduction in alkali-soluble beta-1,3-glucan
      that was accompanied by a modest reduction in beta-1,6-glucan. The gas1 delta
      mutant lacking a 1,3-beta-glucanosyltransferase displayed a similar reduction in
      alkali-soluble beta-1,3-glucan but did not share the beta-1,6-glucan defect,
      indicating that beta-1,6-glucan reduction is not a general phenotype among beta
      1,3-glucan biosynthetic mutants. Overexpression of FKS2 suppressed the killer
      toxin phenotype of fks1 delta mutants, implicating Fks2p in the biosynthesis of
      the residual beta-1,6-glucan present in fks1 delta cells. In addition, eight out
      of 12 fks1ts fks2 delta mutants had altered beta-glucan levels at the permissive
      temperature: the partial killer resistant FKS1F1258Y N1520D allele was severely
      affected in both polymers and displayed a 55% reduction in beta-1,6-glucan, while
      the in vitro hyperactive allele FKS1T605I M761T increased both beta-glucan
      levels. These beta-1,6-glucan phenotypes may be due to altered availability of,
      and structural changes in, the beta-1,3-glucan polymer, which might serve as a
      beta-1,6-glucan acceptor at the cell surface. Alternatively, Fks1p and Fks2p
      could actively participate in the biosynthesis of both polymers as beta-glucan
      transporters. We analysed Fks1p and Fks2p in beta-1,6-glucan deficient mutants
      and found that they were mislocalized and that the mutants had reduced in vitro
      glucan synthase activity, possibly contributing to the observed beta-1,6-glucan
      defects.

PMID- 12185839
TI  - Revisiting the yeast chromosome VI DNA sequence reveals a correction merging
      YFL007w and YFL006w to a single ORF.
AB  - The overall contiguity of the Saccharomyces cerevisiae chromosome VI sequence
      assembly was assessed by systematic long-range PCR, PCR product size
      determination and sequencing. Using S. cerevisiae strain FY1679 total genomic DNA
      as template, 41 overlapping PCR products were generated, covering the complete
      270 kb chromosome VI sequence. Specificity of the PCR products was confirmed by
      direct end-sequencing. No fragment size discrepancies with the published sequence
      were observed, confirming the overall sequence assembly. Gel reads of the PCR
      fragment ends compile to a total of resequenced DNA representing 16% of the
      entire chromosome VI and reveal three single nucleotide differences. One of these
      is an extra G in the protein-coding region of YFL007w. Due to this additional
      nucleotide, the coding sequences of YFL007w and YFL006w become part of a 6432 bp
      ORF. The same sequence also resulted from analysis of strain BY4743. Homologous
      proteins of unknown function found in Candida albicans, Arabidopsis thaliana,
      Caenorhabditis elegans and man, as well as comparative data from published
      transcript profiles of YFL006w and YFL007w, give additional evidence for the
      existence of a single gene at this locus in yeast.

PMID- 12185841
TI  - The hexose transporters of Saccharomyces cerevisiae play different roles during
      enological fermentation.
AB  - We investigated the role of hexose transporters in a Saccharomyces cerevisiae
      strain derived from an industrial wine strain by carrying out a functional
      analysis of HXT genes 1-7 under enological conditions. A strain in which the
      sugar carrier genes HXT1-HXT7 were deleted was constructed and the HXT genes were
      expressed individually or in combination to evaluate their role under wine
      alcoholic fermentation conditions. No growth or fermentation was observed in
      winemaking conditions for the hxt1-7 delta strain. The low-affinity carriers Hxt1
      and Hxt3 were the only carriers giving complete fermentation of sugars when
      expressed alone, indicating that these carriers play a predominant role in wine
      fermentation. However, these two carriers have different functions. The Hxt3
      transporter is thought to play a major role, as it was the only carrier that gave
      an almost normal fermentation profile when produced alone. The hxt1 carrier was
      much less effective during the stationary phase and its role is thought to be
      restricted to the beginning of fermentation. The high-affinity carriers Hxt2,
      Hxt6 and/or Hxt7 were also required for normal fermentation. These high-affinity
      transporters have different functions: hxt2 is involved in growth initiation,
      whereas Hxt6 and/or Hxt7 are required at the end of alcoholic fermentation. This
      work shows that the successful alcoholic fermentation of wine involves at least
      four or five hexose carriers, playing different roles at various stages in the
      fermentation cycle.

PMID- 12185840
TI  - Schizosaccharomyces pombe Pmf1p is structurally and functionally related to Mmf1p
      of Saccharomyces cerevisiae.
AB  - A novel family of small proteins, termed p14.5 or YERO57c/YJGFc, has been
      identified. Independent studies indicate that p14.5 family members are
      multifunctional proteins involved in several pathways, e.g. regulation of
      translation or activation of the protease mu-calpain. We have previously shown
      that Mmf1p, a p14.5 of the budding yeast Saccharomyces cerevisiae, is localized
      in the mitochondria and influences mitochondrial DNA stability. In addition, we
      have demonstrated that Mmf1p is functionally related to p14.5 of mammalian cells.
      To explore further the evolutionary conservation of the mitochondrial function(s)
      of the p14.5s we have extended our study to the fission yeast,
      Schizosaccharomyces pombe. In this organism two p14.5 homologous proteins are
      present: Pmf1p (pombe mitochondrial factor 1) and Hpm1p (homologous Pmf1p factor
      1). We have generated a specific Pmf1p antibody, which recognizes a single band
      of approximately 15 kDa in total cellular extracts. Cellular fractionation
      experiments indicate that Pmf1p localizes in the mitochondria as well as in the
      cytoplasm. We also show that Pmf1p shares several properties of S. cerevisiae
      Mmf1p. Indeed, Pmf1p restores the wild-type phenotype when expressed in delta
      mmf1 S. cerevisiae cells. Deletion of the leader sequence of Pmf1p abrogates its
      ability to localize in mitochondria and to functionally replace Mmf1p. Thus,
      these data together with our previous study show that the mitochondrial
      function(s) of the p14.5 family members are highly conserved in eukaryotic cells.

PMID- 12185842
TI  - Tantalizing Thanatos: unexpected links in death pathways.
AB  - Cell death is most frequently the result of apoptosis, an event that is often
      controlled by mitochondrial membrane permeabilization (MMP). Recent data reveal
      unexpected functional links between apoptosis and autophagic cell death, in the
      sense that MMP can trigger autophagy of damaged mitochondria. Conversely, one of
      the major signal-transducing molecules involved in the activation of autophagy
      during apoptosis--the so-called DAP kinase--can induce cell death through MMP.
      Connections are also emerging between apoptosis, autophagy, replicative
      senescence and cancer-specific metabolic changes.

PMID- 12185843
TI  - Oiling the wheels of the endocytic pathway.
AB  - An ever more complete picture of the organization and function of the endocytic
      pathway is emerging. New mechanisms, and in particular lipid-based mechanisms
      that couple membrane dynamics and sorting, are being unraveled. But the final
      picture is still coming into focus as new membrane domains, cell entry pathways
      and compartments come into view. Of special interest are the recent findings that
      pathogenic agents, in contrast to scientists, seem to have long discovered how to
      subvert membrane specialization to their own advantage.

PMID- 12185844
TI  - How mitochondria import hydrophilic and hydrophobic proteins.
AB  - Most mitochondrial proteins are nuclear encoded and have to be transported into
      the organelle after synthesis on cytosolic ribosomes. Three multimeric protein
      complexes have been identified that import precursor proteins destined for the
      mitochondria: the TOM complex in the outer membrane and two TIM complexes in the
      inner membrane. Recent work has provided a detailed view of the different
      mechanisms operating during the import of the two major classes of mitochondrial
      proteins--hydrophilic proteins with cleavable presequences and hydrophobic
      proteins with multiple internal signals.

PMID- 12185845
TI  - TGF-beta signaling from a three-dimensional perspective: insight into selection
      of partners.
AB  - Members of the transforming growth factor beta (TGF-beta) family, which include
      TGF-beta s, activins and bone morphogenetic proteins (BMPs), are potent
      regulators of cell proliferation, differentiation, migration and apoptosis. They
      act through binding to and activating serine/threonine kinase receptors on the
      cell surface and triggering intracellular signaling pathways in which Smad
      proteins have essential roles. Here, we discuss recent structure-based studies of
      TGF-beta s and BMPs, their receptors, and of Smad proteins, which have unravelled
      insights into ligand specificity, receptor and Smad activation, as well as new
      features of Smads as phosphoserine-binding entities.

PMID- 12185846
TI  - Ubiquitin-mediated proteolysis in plant hormone signal transduction.
AB  - Being sessile organisms, plants usually have little control over their immediate
      growth environment. Responses to environmental and developmental factors need to
      be rapid and finely coordinated to trigger the necessary morphological and
      metabolic changes that ensure plant survival and growth. Many of these adaptive
      responses are mediated by plant hormones. Recent work has shown that ubiquitin
      mediated proteolysis plays an important regulatory role in hormone signaling.

PMID- 12185847
TI  - The endocytic machinery at an interface with the actin cytoskeleton: a dynamic,
      hip intersection.
AB  - Clathrin-mediated endocytosis is the major mechanism by which proteins and
      membrane lipids gain access into cells. Over the past several years, an array of
      proteins has been identified that define the molecular machinery regulating the
      formation of clathrin-coated pits and vesicles. This article focuses on how the
      identification of this machinery has begun to reveal a molecular basis for a link
      between endocytosis and the actin cytoskeleton--a link that had long been
      suspected to exist in mammalian cells but which had remained elusive. In
      particular, I discuss the relationship between actin and three components of the
      endocytic machinery--dynamin, HIPs (huntingtin-interacting proteins) and
      intersectin.

PMID- 12185848
TI  - A new dawn for an old connection: development meets the cell.
AB  - Increasingly, the attention of developmental biologists is being drawn from genes
      and their products towards cells, from processes mediated by linear pathways in
      which one protein regulates the activity of another to events that rely on
      multimolecular machines. Some components of these machines are partially
      redundant, and some have essential functions in general cellular processes. These
      observations invite a reassessment of the uses of genetics for analyzing the cell
      biology of development. In addition, the increasing ability to image live cells
      and their proteins reveals a complex and interesting world, forcing us to deal
      with new variables and objects of study. Here, we provide a glimpse of these
      changes and the challenges they raise.

PMID- 12185849
TI  - Initiating and guiding migration: lessons from border cells.
AB  - Cell migration occurs in many different contexts. Amoebae and other isolated
      cells migrate in culture. In animals, 'professional' migratory cells of the
      immune system constantly survey the body for intruders, whereas other cell types
      perform specific developmentally regulated migrations. One simple model for the
      latter type of event is migration of border cells during Drosophila oogenesis.
      Recent findings have shed light on how border cell fate is induced and on how the
      migration is guided. This article discusses the implications of these studies and
      compares (invasive) migration through a tissue with what is known about cells
      crawling on a flat substratum.

PMID- 12185850
TI  - Mechanisms of spindle positioning: focus on flies and worms.
AB  - Accurate spindle positioning is crucial for spatial control of cell division.
      During metazoan development, coordination between polarity cues and spindle
      position also ensures correct segregation of cell fate determinants. Converging
      evidence indicates that spindle positioning is achieved through interactions
      between cortical anchors and the plus ends of microtubules, generating pulling
      forces acting on spindle poles. This article discusses recent findings that
      indicate how this mechanism might be used for spindle positioning during
      Drosophila and Caenorhabditis elegans development.

PMID- 12185851
TI  - Ephrins in reverse, park and drive.
AB  - Eph receptors and their membrane-anchored ephrin ligands are thought to
      orchestrate cell movements by transducing bidirectional tyrosine-kinase-mediated
      signals into both cells expressing the receptors and cells expressing the
      ligands. Whether the resulting event is repulsion of an axonal growth cone,
      directing the orderly segmentation of hindbrain rhombomere cells or controlling
      angiogenic remodelling, such elaborate and diverse cell movements require
      intricate changes in the actin cytoskeleton, as well as precise regulation of
      cellular adhesion. Recent work by several groups has begun to link ephrin reverse
      signals to intracellular pathways that regulate actin dynamics and might help to
      explain how these ligands function as receptors to direct cell movement, adhesion
      and de-adhesion events.

PMID- 12185852
TI  - David Sabatini--a lifelong fascination with organelles.
AB  - As a pioneer molecular cell biologist, highly skilled in both morphological and
      biochemical approaches, David Sabatini was a key figure in laying the foundation
      for the field of intracellular protein trafficking with his seminal studies on
      cotranslational translocation of nascent polypeptides in the endoplasmic
      reticulum and the intracellular sorting of plasma membrane proteins in polarized
      epithelial cells.

PMID- 12185853
TI  - Echocardiographic assessment of the pulmonary venous flow. An indicator of
      increased pulmonary flow in congenital cardiac malformations.
AB  - OBJECTIVE: To identify the left inferior pulmonary vein as an indirect marker of
      increased pulmonary flow in congenital heart diseases. METHODS: We carried out a
      prospective consecutive study on 40 patients divided into 2 groups as follows: G1
      -20 patients diagnosed with congenital heart disease and increased pulmonary
      flow; G2 (control group)--20 patients who were either healthy or had congenital
      heart disease with decreased or normal pulmonary flow. We obtained the velocity
      time integral of the left inferior pulmonary vein flow, excluding the "reverse A"
      wave, with pulsed Doppler echocardiography. RESULTS: In G1, 19 out of the 20
      patients had well-identified dilation of the left inferior pulmonary vein. No G2
      patient had dilation of the left inferior pulmonary vein. Dilation of the left
      inferior pulmonary vein in conditions of increased pulmonary flow had sensitivity
      of 95%, specificity of 100%, positive predictive value of 100%, and negative
      predictive value of 95% (1 false-negative case). The integral of time and
      velocity of the pulmonary venous flow obtained with pulsed Doppler
      echocardiography was greater in the G1 patients (G1 = 25.0 +/- 4.6 cm versus G2 =
      14.8 +/- 2.1 cm, p = 0.0001). CONCLUSION: The identification of dilation of the
      left inferior pulmonary vein suggests the presence of congenital heart disease
      with increased pulmonary flow. This may be used as an indirect signs of increased
      flow, mainly in malformations of difficult diagnosis, such as atrial septal
      defects of the venous sinus or coronary sinus type.

PMID- 12185854
TI  - Retrospective study of the survival of patients who underwent cardiopulmonary
      resuscitation in an intensive care unit.
AB  - OBJECTIVE: To evaluate clinical and evolutive characteristics of patients
      admitted in an intensive care unit after cardiopulmonary resuscitation,
      identifying prognostic survival factors. METHODS: A retrospective study of 136
      patients admitted between 1995 and 1999 to an intensive care unit, evaluating
      clinical conditions, mechanisms and causes of cardiopulmonary arrest, and their
      relation to hospital mortality. RESULTS: A 76% mortality rate independent of age
      and sex was observed. Asystole was the most frequent mechanism of death, and seen
      in isolation pulmonary arrest was the least frequent. Cardiac failure, need for
      mechanical ventilation, cirrhosis and previous stroke were clinically significant
      (p < 0.01) death factors. CONCLUSION: Prognostic factors supplement the doctor's
      decision as to whether or not a patient will benefit from cardiopulmonary
      resuscitation.

PMID- 12185855
TI  - Can the cardiopulmonary 6-minute walk test reproduce the usual activities of
      patients with heart failure?
AB  - OBJECTIVE: The 6-minute walk test is an way of assessing exercise capacity and
      predicting survival in heart failure. The 6-minute walk test was suggested to be
      similar to that of daily activities. We investigated the effect of motivation
      during the 6-minute walk test in heart failure. METHODS: We studied 12 males, age
      45 +/- 12 years, ejection fraction 23 +/- 7%, and functional class III. Patients
      underwent the following tests: maximal cardiopulmonary exercise test on the
      treadmill (max), cardiopulmonary 6-minute walk test with the walking rhythm
      maintained between relatively easy and slightly tiring (levels 11 and 13 on the
      Borg scale) (6EB), and cardiopulmonary 6-minute walk test using the usual
      recommendations (6RU). The 6EB and 6RU tests were performed on a treadmill with
      zero inclination and control of the velocity by the patient. RESULTS: The values
      obtained in the max, 6EB, and 6RU tests were, respectively, as follows: O2
      consumption (ml.kg-1.min-1) 15.4 +/- 1.8, 9.8 +/- 1.9 (60 +/- 10%), and 13.3 +/-
      2.2 (90 +/- 10%); heart rate (bpm) 142 +/- 12, 110 +/- 13 (77 +/- 9%), and 126 +/
      11 (89 +/- 7%); distance walked (m) 733 +/- 147, 332 +/- 66, and 470 +/- 48; and
      respiratory exchange ratio (R) 1.13 +/- 0.06, 0.9 +/- 0.06, and 1.06 +/- 0.12.
      Significant differences were observed in the values of the variables cited
      between the max and 6EB tests, the max and 6RU tests, and the 6EB and 6RU tests
      (p < 0.05). CONCLUSION: Patients, who undergo the cardiopulmonary 6-minute walk
      test and are motivated to walk as much as they possibly can, usually walk almost
      to their maximum capacity, which may not correspond to that of their daily
      activities. The use of the Borg scale during the cardiopulmonary 6-minute walk
      test seems to better correspond to the metabolic demand of the usual activities
      in this group of patients.

PMID- 12185856
TI  - Analysis of the association between apolipoprotein E polymorphism and
      cardiovascular risk factors in an elderly population with longevity.
AB  - OBJECTIVE: To establish the allelic and genotypic frequencies related to
      apolipoprotein E (ApoE) polymorphism and association of the genotypes with risk
      factors and cardiovascular morbidity in an elderly population with longevity.
      METHODS: We analyzed 70 elderly patients aged 80 years or more who were part of
      the Projeto Veranopolis. We used the gene amplification technique through the
      polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and
      cleavage with the restriction enzyme Hha I to identify the ApoE genotypes. The
      most frequent genotypes were compared considering biological variables and
      cardiovascular risks and morbidity. RESULTS: The frequencies of the E2, E3, and
      E4 alleles were 0.05, 0.84, and 0.11, respectively, and of the genotypes were as
      follows: E3E3 (0.70), E3E4 (0.22), E2E3 (0.06), and E2E2 (0.02). Individuals with
      the E3E4 had a mean age greater than those with the E3E3. No association was
      observed between the genotypes and the variables analyzed, except for obesity,
      which was associated with the E3E3 genotype. Individuals with the E3E4 genotype
      had high levels of LDL-cholesterol and fibrinogen as compared with those with the
      E3E3 genotype. CONCLUSION: The results suggest that the E4E4 genotype may be
      associated with early mortality. A balance between the protective or neutral
      factors and the cardiovascular risk factors may occur among the individuals with
      different genotypes, attenuating the negative effects of the E4 allele.

PMID- 12185857
TI  - Pericardial effusion with cardiac tamponade as a form of presentation of primary
      hypothyroidism.
AB  - The authors describe a case of pericardial effusion accompanied by cardiac
      tamponade caused by primary hypothyroidism. Diagnosis was made by exclusion,
      because other causes of cardiac tamponade are more frequent. Emergency treatment
      of cardiac tamponade is pericardiocentesis (with possible pericardial window),
      and, after stabilization, performance of hormonal reposition therapy with L
      thyroxin.

PMID- 12185858
TI  - Primary cardiac angiosarcoma. A therapeutical dilemma.
AB  - Cardiac angiosarcomas are malignant tumors that almost invariably have a short
      and fatal evolution. The therapeutic approach includes surgery, chemotherapy, and
      radiation therapy, alone or in combination. Heart transplantation is an
      attractive option in nonresectable tumors, even though the current experience is
      still limited. However, in most patients, the diagnosis is still established
      late, and survival is only slightly altered by the proposed treatments, mainly
      due to previously existing and undetected metastases. We report a case that
      illustrates the therapeutic dilemma faced with this neoplasia, and we discuss the
      case based on a literature review.

PMID- 12185859
TI  - Multiple embolism in a female patient with infective endocarditis. Low back pain
      and hematuria as the initial clinical manifestations.
AB  - A 59-year-old female patient with mitral valve prolapse and a previous history of
      lumbosacral spondyloarthrosis and lumbar disk hernia had an episode of infective
      endocarditis due to Streptococcus viridans, which evolved with peripheral
      embolism to the left kidney, spleen, and left iliac artery, and intraventricular
      cerebral hemorrhage. Her clinical manifestations were low back pain and
      hematuria, which were initially attributed to an osteoarticular condition.
      Infective endocarditis is a severe polymorphic disease with multiple clinical
      manifestations and it should always be included in the differential diagnosis by
      clinicians.

PMID- 12185860
TI  - [To consult, to diagnose and to treat].

PMID- 12185861
TI  - [Anatomoclinical correlation. Case 3/2000--fever and convulsion follow-up by coma
      in a 60 years old woman with chronic rheumatic disease].

PMID- 12185862
TI  - [Clinicoradiological correlation. Case 6/2002 - Instituto do Coracao do Hospital
      das Clinicas da FMUSP].

PMID- 12185863
TI  - [Percutaneous interventions in congenital heart disease].

PMID- 12185864
TI  - [The adipose tissue in the genesis of hypertension and atherosclerotic
      cardiovascular disease. An emerging concept].

PMID- 12185865
TI  - [Cochlear implants. Royal Commission for Prevention and Attention to Handicapped
      Persons].

PMID- 12185866
TI  - [Stability of auditory thresholds during the first 5 weeks after stapedectomy].
AB  - To assess repeatability of audiological test performed every week during the
      first month post-stapedectomy, audiometry was performed to 21 patients with
      otosclerosis (mean age 37.8 years, S.D. 9.29), every week, during the 2 weeks
      prior to stapedectomy and during the first 5 weeks and at week 12 after
      stapedectomy. Repeatability of the audiological test was evaluated comparing the
      difference between the audiological evaluations performed before the surgery and
      the difference between each consecutive pair of audiological evaluations after
      the surgery, using Bland & Altman method and ANOVA, allowing for 5% of
      significance. Before the surgery, audiological thresholds, using head phones,
      were repeatable for low (125-500 Hz), mid (500-2000 Hz) and high (2000-8000 Hz)
      frequencies in 95% of the patients. After the surgery, repeatability of air
      conduction thresholds for the low frequency band was evident from the 2nd week,
      for the mid frequency band was evident from the 3rd week and for the high
      frequency band from the 4th week. The gain observed at week 5 after surgery was
      similar to the gain observed at week 12. In conclusion, in this study, stable air
      conduction auditory thresholds were obtained during the first month after
      stapedectomy.

PMID- 12185867
TI  - [Intra-tympanic gentamicin in the treatment of Meniere's disease: preliminary
      results ].
AB  - In the majority of patients suffering of Meniere's disease, medical treatment is
      sufficient to control symptoms, albeit, in a small number of them, the high
      intensity and frequency of vertigo spells makes necessary to adopt more
      aggressive measures, like intratympanic or general aminoglycoside administration,
      as well as surgical procedures. We present a prospective and longitudinal
      descriptive study with the results of intratympanic gentamycin in 24 patients
      labeled of Meniere's disease in the Otolaryngology Department of "Miguel Servet
      Hospital" in the last two years, after a follow-up period of more than a year,
      during which controlled medical treatment had been proved unsuccesfull. We go
      over the efficacy in terms of frequency of vertigo crisis, audition average,
      logoaudiometry and functional level. We obtained good results over vertigo
      control (types A and B of the objective criteria based in the improvement index
      after treatment) in 16 out of the 24 patients (66.6%), (13 were type A with total
      absence of crisis and 3 were type B) and an acceptable result (type C) in three
      of them (12.5.%). In the other five patients (20.83%) results were disappointing
      (types D and E) compelling to apply surgical treatment. We have tried to evaluate
      intratympanic gentamycin as an alternative treatment to more aggressive technics
      and we consider it to be a good option, with a low risk and scarce complications
      in the no pharmacologically controlled Meniere's disease patients.

PMID- 12185868
TI  - [The value of waiting in spontaneous remission of recurrent tonsillitis without
      associated adenoid pathology].
AB  - In order to assess the rate of spontaneous remission in children with recurrent
      acute tonsillitis (RAT), we revised the pediatric patients who were seen between
      1994 and 1999. For this purpose, 123 cases that were on the waiting list for
      tonsillectomy under the indication of RAT without associated adenoid disease were
      selected. Only 23 (18.7%) of the children who were included in the study were
      removed from the waiting list after a mean time of 9 months because of
      spontaneous remission of the disease. Thus, there is no justification for
      claiming that long waiting lists for tonsillectomy are frequently associated with
      spontaneous remission of RAT.

PMID- 12185869
TI  - [Comparative study of the use of manual and mechanical suturing in the closure of
      the mucosal defect in total laryngectomy].
AB  - With the present study we try to achieve an objective confirmation of the
      efficacy given by the mechanical suture in the closing of the pharyngeal defect
      following a total laryngectomy against the conventional manual suture with
      absorbable material. Therefore we have studied three random groups of patients:
      in the first one we include those who had a manual suture (n = 50), in the second
      one those who had performed a mechanical suture with closed technique (n = 38)
      and in the third one those who had a mechanical suture with an open technique (n
      = 12). We have checked that mechanical suture with a closed technique improves
      significantly the surgical length (212 minutes), the beginning of the oral
      feeding (10.73 days) and the time of in-hospital stay (13.5 days). Mechanical
      sutures with a closed technique also reduce the rate of complications such as
      fistulae (5.26%), infection (0%) and haemorrhage (0%).

PMID- 12185870
TI  - [Balloon catheter dilatation in pharyngo-esophageal stenosis].
AB  - On the scarring strictures at the level of the pharyngo-esophageal junction, for
      example following surgery for pharyngo-laryngeal tumours, the treatment was
      traditionally the use of transoral dilators, as the metallic spark plugs or
      olives. At present the balloon catheters are the election technique for all
      cases. The advantages for the balloon catheters versus the traditional methods
      are the smaller morbidity and mortality, the effectiveness, simplicity and little
      cost. We show the protocol done in our center for the dilation of these
      strictures.

PMID- 12185871
TI  - [Cochlear hemorrhage. Unusual cause of sudden sensorineural deafness].
AB  - Sudden sensorineural hearing loss (SNHL) caused by intralabyrinthine hemorrhage
      is a rare entity usually associated to patients with previous pathological
      factors, such as blood dyscrasias, anticoagulant therapy and local hemorrhagic
      pathologies. We report the first-published case of sudden-onset deafness due to
      cochlear hemorrhage in a patient with no previous pathologies. We describe the
      history, diagnosis and follow-up of this patient in comparison to others
      previously published.

PMID- 12185872
TI  - [Presentation of 2 cases of sudden deafness in patients with sickle-cell anemia
      and trait].
AB  - We report two cases of sudden deafness which appeared during vaso-occlusive
      crisis of a sickle cell anaemia (homozygous form of disease) and a sickle cell
      trait (heterozygous form) in two males aged sixteen and twenty-two, respectively.
      A high erythrocyte aggregability and low deformability were proved in both young
      men. Although hearing disorders have been reported in this disease, a sudden
      onset is not common. The treatment used was useful in the removal of painful
      crisis and infections, but deafness did not improve in either of then.

PMID- 12185873
TI  - [Susac syndrome as a cause of sensorineural hearing loss].
AB  - Susac's syndrome is an extremely rare clinical manifestation characterized by the
      triad of fluctuating sensorineural hearing loss, sudden visual loss and
      encephalopathy. Probably underdiagnosed, it affects young women who start the
      clinical history with headache, visual and hearing disturbances, with
      neurological findings in MRI. With unknown aetiology, pathogenesis is based on
      arteriolar microinfarcts in retina, cochlea, and grey and white matter in the
      brain. Treatment is, as stated in the bibliography and our experience,
      intravenous high doses of steroids followed by oral steroids together with
      hyperbaric oxygen to minimize ischaemic lesions. Aspirin associate to nimodipine
      has been useful to date in the treatment of our patient. We present a case and
      review the existing literature.

PMID- 12185874
TI  - ["Irritative" pathology of the external auditory canal and decreased sound
      sensation].
AB  - We have not found in the literature an explanation for the intermittent and
      transient decreased lesser hearing sensation in patients with dysesthesia of the
      external auditory canal (EAC). In this paper we offer a possible explanation for
      it. Our hypothesis is that the stimulation of the sensory fibers of the
      trigeminal and facial nerves in the EAC is able to increase the stiffness of the
      ossicular chain by means of a reflex stimulation of malleus and stapes muscles.
      This intermittent and transient increase of the ossicular stiffness could explain
      the intermittent and transient decrease of hearing sensation in these patients.

PMID- 12185875
TI  - Posterior laryngitis: where are we?

PMID- 12185876
TI  - Posterior laryngitis: effects of treatment with omeprazole alone.
AB  - OBJECTIVE: To evaluate the effect of omeprazole treatment on the symptoms and
      lesions of patients with posterior laryngitis (PL). PATIENTS AND METHOD: Twenty
      one patients with a clinical and laryngoscopic diagnosis of PL were studied.
      Results for each laryngeal symptom (dysphonia, hoarseness, cough, foreign body
      sensation, and burning) and laryngoscopic finding (mucus stasis, erythema,
      oedema, hypertrophy, ulceration, and granulation) at baseline, 12 weeks after
      treatment with omeprazole, 20 mg twice daily, and 12 weeks after treatment
      discontinuation were compared. No changes in their hygienic-dietary or postural
      habits were recommended. RESULTS: A reduction in symptom severity and frequency
      was observed (p < 0.05), as well as in the severity of laryngoscopic findings (p
      < 0.05)--except for granulation--immediately after treatment discontinuation. A
      relapse of laryngoscopic findings was seen at 12 weeks after treatment
      discontinuation (p < 0.01). The trend towards symptom recurrence was not
      significant. CONCLUSION: Treatment with omeprazole alone modifies clinical
      manifestations and endoscopic findings in patients with PL. Controlled clinical
      trials with a high number of patients and longer-term follow-up are needed to
      define the best therapeutic regimen for these patients.

PMID- 12185877
TI  - Experimental model for the study of perianastomotic recurrence in colorectal
      cancer.
AB  - OBJECTIVE: To determine if an experimental model is valid for the study of
      perianastomotic recurrence in colorectal cancer, comparing it with previous
      experimental models. METHODS: Experimental study with 40 male Sprague-Dawley
      rats, assigned to one of the study groups: control group (n = 20), with
      manipulation of large descending bowel, and colonic anastomosis group (n = 20),
      with colonic section and colocolic anastomosis. After pharmacological
      carcinogenesis with 1-2 dimethylhydrazine at a weekly dose of 25 mg/kg for 18
      weeks, colonic tumours were studied at the 20th postoperative week. RESULTS:
      Number of tumours, colic tumoral area and percentage of colic tumoral area were
      greater in the colonic anastomosis group. In this group with colonic anastomosis
      all determinations were higher at the perianastomotic large bowel. CONCLUSIONS:
      We think this experimental model may be the best model to study perianastomotic
      recurrence in large bowel cancer. The high incidence of induced colic tumours and
      their location at the perianastomotic area offer a good field to determine
      response to experimental manipulations on colorrectal cancer.

PMID- 12185878
TI  - Pre-endoscopic prognostic factors in non-varicose upper gastrointestinal
      bleeding. Development of a predictive algorithm.
AB  - OBJECTIVE: Upper gastrointestinal or digestive bleeding (UDB) is a common problem
      requiring hospitalization and implying important morbidity-mortality. The aim of
      the present study is to identify clinical and laboratory factors predictive of a
      serious course of non-varicose UDB, based on the development of a simple
      algorithm for application in the clinical setting. METHODS: A longitudinal study
      was made of 803 hospitalized patients with non-varicose UDB. Clinical and
      laboratory parameters were recorded in the Emergency Service before endoscopy. A
      first non-conditional logistic regression model was developed, including those
      variables exhibiting a greater capacity for predicting a serious outcome. This
      model was posteriorly simplified to facilitate clinical application. The
      prognostic performance was estimated by calculating the area under the ROC curve.
      RESULTS: The initial predictive model included 11 variables, with an area under
      the ROC curve of 0.74 (95%CI: 0.71-0.77), while in the second model these same
      variables were dichotomized, exhibiting an area under the ROC curve of 0.74
      (95%CI: 0.70-0.77). Based on the corresponding regression coefficients, the
      prognostic variables were classified as either major (shock, liver disease,
      anticoagulant therapy, urea/creatinine ratio > 62) or minor (hematocrit < 33%,
      renal failure, presentation as hematemesis and melenas, systolic arterial
      pressure < 110 mmHg, regular alcohol consumption, a history of UDB, and a patient
      age of > 75 years). UDB was predicted to take an unfavorable course in the
      presence of one major factor or two minor factors. CONCLUSIONS: The proposed
      algorithm includes pre-endoscopy clinical and laboratory variables, and allows
      early classification of patients with non-varicose UDB in terms of their possible
      clinical course.

PMID- 12185879
TI  - Prescribing exercise for hepatitis.
AB  - Physical exercise induces effects involving various organ systems in the body.
      These changes are both immediate and permanent. Such adaptations and changes will
      be beneficial for most individuals, provided they are included within a physical
      activity regimen suited to conform to the status and needs of each target
      subject. This is specially relevant when exercise is prescribed for a person who
      is suffering from a liver condition, and who in addition is receiving drug
      therapy.

PMID- 12185881
TI  - [Cytomegalovirus and perforation complication a Salmonella colitis in an
      immunocompetent patient].

PMID- 12185880
TI  - Interferon-alpha induced transient thyroid dysfunction in hepatitis C.
AB  - We report the case of thyroid dysfunction that developed in a 36-year-old female
      patient who required combination therapy with interferon and ribavirine for
      chronic hepatitis C. Firstly, she suffered a hyperthyroidism followed by a
      hypothyroidism stage requiring thyroxine replacement therapy. Nevertheless,
      combination treatment was not discontinued, reaching a sustained biochemical and
      virological response. The pathogenesis of autoimmune diseases in patients with
      Hepatitis C virus infection and interferon therapy is not clear, but usually
      these disorders are reversible and only require supervision and treatment if
      clinical or laboratory abnormalities are present.

PMID- 12185882
TI  - [Submucosal impression of the stomach like a submucosal tumor: diagnosis by
      endoscopic ultrasound].

PMID- 12185883
TI  - [A fatal case of diagnostic paracentesis: hematoma of the rectus abdominis].

PMID- 12185884
TI  - [Bochdaleck's hernia in an adult].

PMID- 12185885
TI  - [Acute hepatic and renal failure due to piroxicam use].

PMID- 12185886
TI  - [Olfactory disorders and gastroesophageal reflux disease. An unusual case].

PMID- 12185887
TI  - [Esophagodiverticulostomy for the treatment of Zenker's diverticulum].

PMID- 12185888
TI  - Sample size re-estimation in cluster randomization trials.
AB  - Cluster randomization trials in which families are the unit of allocation are
      commonly adopted for the evaluation of disease prevention interventions. Sample
      size estimation for cluster randomization trials depends on parameters that
      quantify the variability within and between clusters and the variability in
      cluster size. Accurate advance estimates of these nuisance parameters may be
      difficult to obtain and misspecification may lead to an underpowered study. Since
      families are typically recruited over time, we propose using a portion of the
      data to estimate the nuisance parameters and to re-estimate sample size based on
      the estimates. This extends the standard internal pilot study methods to the
      setting of cluster randomization trials. The effect of this design on the power,
      significance level and sample size is analysed via simulation and is shown to
      provide a flexible and practical approach to cluster randomization trials.

PMID- 12185890
TI  - Study control, violators, inclusion criteria and defining explanatory and
      pragmatic trials.
AB  - Important differences between explanatory and pragmatic studies were originally
      argued by Schwartz and Lellouch. Three important differences between the two
      types of study involve study control, study violators and inclusion criteria. It
      was originally argued that explanatory studies are highly controlled, and
      pragmatic studies may be looser and more like 'real life'. It was argued that an
      explanatory study should only analyse those receiving treatment, and a pragmatic
      study would analyse all randomized patients. Explanatory trials are said to use
      homogeneous groups, and pragmatic studies have less selection (better
      generalizability). Some suggestions are put forward to update the original
      distinctions between these two attitudes for future study design. Poor study
      control is undesirable (but might be necessary) and should not be welcomed as
      pragmatic. The intention-to-treat strategy is now considered as standard for
      nearly all trials. Homogeneity is a red herring for studies in humans. Inclusion
      criteria should be minimized and they should not be used to justify claims of
      representativeness. Routine criticism of randomized controlled trials for being
      unrepresentative is unwarranted. We should accept that most trials in humans are
      'explanatory'. The division line should be moved, so that pragmatic studies are
      in the domain of non-therapeutics and complex treatments.

PMID- 12185889
TI  - Clinical trials of behavioural interventions with heterogeneous teaching subgroup
      effects.
AB  - Behaviour modification is often delivered to teaching subgroups. For example,
      experimental and control smoking cessation programmes may be given to 15 classes
      (subgroups) with 10 (otherwise independent) individuals. We present general
      statistical tests and power estimates to compare continuous outcomes from two
      interventions in settings where the magnitude of teaching subgroup heterogeneity,
      number of subgroups and subgroup size can differ between intervention arms. An
      application is made to data from a trial to reduce disease-transmitting sexual
      behaviour. The statistical impact of teaching subgroup heterogeneity effect
      increases as the (a) number of participants in a subgroup increases, and (b)
      ratio of 'averaged experimental and control subgroup effect variance' to study
      subject variance increases. If plausible levels of subgroup teaching effect
      heterogeneity are ignored, the true sizes of tests with nominal 0.05 two-sided
      type I errors range from 0.055 to 0.47, while when planning studies, estimated
      sample sizes are only 11.1-95.2 per cent of the true requirements.

PMID- 12185891
TI  - A note on ANOVA assumptions and robust analysis for a cross-over study.
AB  - Analysis of variance (ANOVA) methods are usually applied to analyse continuous
      data from cross-over studies. The analysis, however, may not have appropriate
      type I error when certain assumptions are violated. In this paper, we first
      clarify a conventionally minimum set of assumptions that validate the F-tests of
      ANOVA models for cross-over studies. We then provide a practical
      verification/remedy procedure based upon the theoretical developments. By
      applying the verification/remedy procedure, more robust analysis results can be
      expected from the ANOVA models.

PMID- 12185892
TI  - Prediction of survival and opportunistic infections in HIV-infected patients: a
      comparison of imputation methods of incomplete CD4 counts.
AB  - In evaluating the risk of mortality or development of opportunistic infections in
      HIV-infected patients, the number of CD4 lymphocyte cells per cubic millimetre of
      blood is widely recognized as one of the best available predictors of such future
      events. However, its usefulness is limited by the incompleteness and variability
      of such CD4 measurements during follow-up. Because of these limitations, analysis
      of such data requires the missing measurements to be 'filled in' or the patients
      without them to be excluded. We consider multiple imputation of CD4 values based
      partly on information from other health status measures such as haemoglobin, as
      well as on the event status of interest. These alternative health status measures
      are also considered as possible independent predictors of survival endpoints. Our
      work is motivated by a cohort of 1530 patients enrolled in two AIDS clinical
      trials. We compare our approach to other strategies such as basing evaluation of
      risk on baseline CD4, the last measured CD4 before an event, or a time-dependent
      covariate based on carrying the last CD4 value forward; we conclude with a strong
      recommendation for multiple imputation.

PMID- 12185893
TI  - Estimating risk and rate levels, ratios and differences in case-control studies.
AB  - Classic (or 'cumulative') case-control sampling designs do not admit inferences
      about quantities of interest other than risk ratios, and then only by making the
      rare events assumption. Probabilities, risk differences and other quantities
      cannot be computed without knowledge of the population incidence fraction.
      Similarly, density (or 'risk set') case-control sampling designs do not allow
      inferences about quantities other than the rate ratio. Rates, rate differences,
      cumulative rates, risks, and other quantities cannot be estimated unless
      auxiliary information about the underlying cohort such as the number of controls
      in each full risk set is available. Most scholars who have considered the issue
      recommend reporting more than just risk and rate ratios, but auxiliary population
      information needed to do this is not usually available. We address this problem
      by developing methods that allow valid inferences about all relevant quantities
      of interest from either type of case-control study when completely ignorant of or
      only partially knowledgeable about relevant auxiliary population information.

PMID- 12185894
TI  - Small-sample adjustments in using the sandwich variance estimator in generalized
      estimating equations.
AB  - The generalized estimating equation (GEE) approach is widely used in regression
      analyses with correlated response data. Under mild conditions, the resulting
      regression coefficient estimator is consistent and asymptotically normal with its
      variance being consistently estimated by the so-called sandwich estimator.
      Statistical inference is thus accomplished by using the asymptotic Wald chi
      squared test. However, it has been noted in the literature that for small samples
      the sandwich estimator may not perform well and may lead to much inflated type I
      errors for the Wald chi-squared test. Here we propose using an approximate t- or
      F-test that takes account of the variability of the sandwich estimator. The level
      of type I error of the proposed t- or F-test is guaranteed to be no larger than
      that of the Wald chi-squared test. The satisfactory performance of the proposed
      new tests is confirmed in a simulation study. Our proposal also has some
      advantages when compared with other new approaches based on direct modifications
      of the sandwich estimator, including the one that corrects the downward bias of
      the sandwich estimator. In addition to hypothesis testing, our result has a clear
      implication on constructing Wald-type confidence intervals or regions.

PMID- 12185895
TI  - Improved approximate confidence intervals for the mean of a log-normal random
      variable.
AB  - Data analysts often compute approximate 100 (1-alpha) per cent confidence
      intervals for the mean of a log-normal random variable due to the computational
      effort required for exact intervals. We evaluate two simple approximations and
      demonstrate that the probabilities with which the intervals fail to capture the
      population mean (that is, the coverage error) can range from well above the
      desired level, alpha, to very near zero in small to moderate sample sizes (n < or
      = 100). The performance of a more sophisticated approximation, implemented via
      numerical integration or bootstrap sampling, is noticeably improved, but also
      suffers from coverage errors that are too large when n < or = 25. A new procedure
      is developed which outperforms existing approximations. Computing these improved
      intervals requires the integration of standard distribution functions. The
      calculations are straightforward, however, and lead to satisfactory coverage
      errors for n as small as 5. A related method that avoids the integration step
      generally outperforms existing simple approximations for n < or = 100, while
      maintaining the coverage error at or below alpha. Programs to implement the new
      procedures are provided in an Appendix.

PMID- 12185896
TI  - Zero-inflated models for regression analysis of count data: a study of growth and
      development.
AB  - Poisson regression is widely used in medical studies, and can be extended to
      negative binomial regression to allow for heterogeneity. When there is an excess
      number of zero counts, a useful approach is to used a mixture model with a
      proportion P of subjects not at risk, and a proportion of 1--P at-risk subjects
      who take on outcome values following a Poisson or negative binomial distribution.
      Covariate effects can be incorporated into both components of the models. In
      child assessment, fine motor development is often measured by test items that
      involve a process of imitation and a process of fine motor exercise. One such
      developmental milestone is 'building a tower of cubes'. This study analyses the
      impact of foetal growth and postnatal somatic growth on this milestone,
      operationalized as the number of cubes and measured around the age of 22 months.
      It is shown that the two aspects of early growth may have different implications
      for imitation and fine motor dexterity. The usual approach of recording and
      analysing the milestone as a binary outcome, such as whether the child can build
      a tower of three cubes, may leave out important information.

PMID- 12185897
TI  - Analysis of mixed categorical data in 2 x K contingency tables.
AB  - 2 x K contingency tables having both ordinal and nominal categories are often
      encountered in various types of studies. Such data are referred to as 'mixed'
      categorical data in this article. To apply a method for ordered categorical data
      one has to discard the nominal categories, and to apply a method for nominal
      categories one has to discard the ordering information inherent in the ordered
      categories. Therefore, investigators often either discard observations in nominal
      categories or discard the ordering of the categories before analysing such data.
      Some information will be lost in both approaches. A method for analysing data in
      2 x K 'mixed' tables is proposed in this paper which can be considered as an
      extension of well known methods for nominal and ordered categories. The proposed
      method utilizes observations in the nominal categories as well as the ordering
      information. If all the categories were ordered then the proposed method reduces
      to the trend test, and if all the categories were nominal then the proposed
      method reduced to Pearson's chi-square test.

PMID- 12185898
TI  - An empirical comparison of record linkage procedures.
AB  - We consider the problem of record linkage in the situation where we have only non
      unique identifiers, like names, sex, race etc., as common identifiers in
      databases to be linked. For such situations much work on probabilistic methods of
      record linkage can be found in the statistical literature. However, although many
      groups undoubtedly still use deterministic procedures, not much literature is
      available on deterministic strategies. Furthermore, there appears to exist almost
      no documentation on the comparison of results for the two strategies. In this
      work we compare a stepwise deterministic linkage strategy with a probabilistic
      strategy, as implemented in AUTOMATCH, for a situation in which the truth is
      known. The comparison was carried out on a linkage between medical records from
      the Regional Perinatal Intensive Care Centers database and educational records
      from the Florida Department of Education. Social security numbers, available in
      both databases, were used to decide the true status of each record pair after
      matching. Match rates and error rates for the two strategies are compared and a
      discussion of their similarities and differences, strengths and weaknesses is
      presented.

PMID- 12185900
TI  - [Stapedectomy: long term results].
AB  - Stapedectomy, with its most innovatory variations, constitutes the treatment of
      choice for otoesclerosis. Short term results are spectacular, getting GAP
      closures of less than 5 dB approximatelly in 94% patients, variations depending
      on the authors. Long term follow up check results show a gradual auditory
      deterioration. The aim of this study is to audiometric evolution of patients
      operated of stapedectomy 7 to 10 years ago in our department and to correlate the
      results with those obtained by other authors, in an attempt to unify conclusions.

PMID- 12185899
TI  - [Inactivation of p53 and amplification of cyclin D1 in squamous cell carcinomas
      of the head and neck].
AB  - P53 and CCND1 (cyclin D1) genes play a critical role in the cell cycle
      regulation. Abnormalities of these genes are frequent in different types of
      cancers, including those of the head and neck. The aim of this work is to
      investigate whether P53 inactivation (determined by loss of heterozygosity
      analysis) is related to CCND1 gene amplification (determined by differential PCR
      analysis), and if these alterations are correlated with clinical outcome in a
      series of 56 patients with squamous cell carcinoma of the head and neck. Loss of
      heterozygosity of the P53 gene was found in 39 cases (70%) and CCND1
      amplification in 17 cases (30%). Both abnormalities together were found in 11
      cases (20%), without a significant association between them (P = 0.83). No
      relationship was found between P53 inactivation, the clinico-pathological
      parameters analyzed and the clinical outcome. CCND1 amplification was associated
      with advanced T-stages (P = 0.02), nodal metastases (P = 0.01) and a decreased
      survival (P = 0.002). The combination of both abnormalities shows a pattern that
      seems to be additive, since it was associated with an increase in tumor
      recurrences and a decrease in survival that was higher than for either of them
      individually. In conclusion, P53 and CCND1 abnormalities are frequent in squamous
      cell carcinomas of the head and neck. The combined analysis of these
      abnormalities seems to be more informative than either of them individually and
      may have a prognostic value in these carcinomas.

PMID- 12185902
TI  - [Relation between clinical symptoms and the results of a computerized dynamic
      posturography].
AB  - The computerized dynamic posturography (CDP) is a quantitative method for the
      evaluation of balance function under different conditions that simulates the ones
      found in normal life. Its applications are centered in the diagnosis and
      rehabilitation of balance dysfunction. We report a descriptive study on 96
      patients with balance disorders who underwent a CDP, stablishing a relation
      between their main symptoms and the results in the test. A high percentage of
      patients with symptoms that suggested peripheral vestibular pathology did not
      present alterations at this level by means of the CDP. However a considerable
      number of patients who referred symptoms classically related to a non vestibular
      origin did show an alteration at this level.

PMID- 12185901
TI  - [Is hearing preservation feasible with the retrosigmoid approach?].
AB  - The main advantages of the retrosigmoid approach are fast and good visualization
      of the brainstem structures and the possibility to remove tumors of all sizes.
      Hearing preservation, although possible, is not always achieved. The aim of this
      study is to present our experience with the retrosigmoid approach for acoustic
      neuroma resection, emphasizing our hearing results. The notes of 56 cases of
      acoustic neuroma removed through a the retrosigmoid approach were reviewed. Tumor
      size ranged from 8 to 50 mm (mean 24 mm). Considering patients with preoperative
      serviceable hearing, postoperative serviceable and measurable hearing was
      achieved in 13.3% and 26.7% of cases respectively. No tumor recurrence occurred
      in our series. The retrosigmoid approach is a reliable surgical procedure for
      most vestibular schwannoma. However, hearing preservation results may be
      unsatisfactory and show wide differences depending on selection criteria and the
      hearing terminology used. Concerns about hearing preservation should not be the
      deciding factor for using this approach.

PMID- 12185903
TI  - [Acoustic voice analysis: reliability of a set of multi-dimensional parameters].
AB  - A correlational study of the reliability of acoustic voice parameters was made of
      148 healthy adults. Acoustic analysis was performed with MDVP-Multi-Dimensional
      Voice Program implemented in a CSL-Computerized Speech Lab of Kay Elemetrics. A
      set of 29 voice parameters were obtained from two samples of sustained vowel /a/
      recorded from each subject. General results separated by sex are showed and the
      test-retest reliability in each pair of measures was calculated. Data show a high
      intra-subject stability of Frequency Fundamental parameters; acceptable stability
      in parameters of Frequency and Amplitude Perturbation, Noise, Subharmonics and
      Voice irregularities; and a very low consistency in Tremor parameters. Parameters
      related with shimmer were more reliable than parameters related with jitter.
      According to results several conclusions are reported.

PMID- 12185904
TI  - [Clinical and functional analysis of long-term results of
      uvulopalatopharyngoplasty].
AB  - In order to evaluate the clinical and functional effectiveness of
      uvulopalatopharyngoplasty (UPPP) in chronic roncopathy, we studied the subjective
      improvement of operated patients and compared to pulsioximetry findings before
      and after surgery. A follow-up was made on 72 patients entitled of chronic
      roncopathy--51 with obstructive sleep apnea syndrome (OSAS) and 21 with simple
      snoring-, for a mean period of time of 41 months. Preoperatory study included on
      ENT exploration, fibre optic endoscopy, Muller maneuver, pharyngeal CT, value of
      daytime sleepiness with Epworth's scale, espirometry and pulsioximetry, and the
      postoperatory study included of pulsioximetry and a health questionnaire over
      snoring and daytime sleepiness. Snoring improved or disappeared in 13 of 21
      patients (61.8%), and daytime sleepiness did it in 26 of 39 (66.6%). Therapeutic
      failure in snoring was mainly due to an increase in the body mass index. After
      UPPP in OSAS, only 21 patients (41.1%) showed all positive response criteria
      (decrease into ODI > or = 50% or in absolute values < 6, CT 90% < 1%, and SaO2
      Min > or = 85%). UPPP failed in long term evaluation in the rest of individuals.
      Patient selection is mandatory to optimize clinical response of UPPP for snoring,
      without OSAS success depends on body mass index, respiratory disturbances ratios
      and the eventual presence of another upper airways collapses below velopharyngeal
      segment.

PMID- 12185905
TI  - [Mastoid cholesterol granuloma with intracranial invasion].
AB  - We report a case of antral-mastoid cholesterol granuloma, invading the middle
      cranial fossa, clinically showing a sudden onset of neurological symptoms. The
      histopathologic, diagnostic, and therapeutic aspects of this lesion are
      commented.

PMID- 12185906
TI  - [An exceptional form of cranio-facial fibrous dysplasia: fibrous dysplasia of
      middle turbinate].
AB  - Fibrous dysplasia is a rare bone disease that can be misdiagnosed because of the
      slowness of its symptoms. Although it is a benign disease its clinical behaviour
      can be severe, with possibility of local growth and malignant degeneration into
      osteosarcoma. An uncommon case of fibrous dysplasia is reported, affecting only
      the middle turbinate. Diagnostic and therapeutic problems are discussed.

PMID- 12185907
TI  - [Extra-naso-pharyngeal angiofibroma: report of a new case and review of
      literature].
AB  - Juvenile nasopharyngeal angiofibromas are vascular neoplasms, which originate
      characteristically in the posterior lateral wall of the nasopharynx. Although
      angiofibromas extend beyond the nasopharynx commonly, sometimes they can have
      their origin outside nasopharynx. We present an unusual case of
      extranasopharyngeal angiofibroma. A high level of suspicion is essential for an
      adequate diagnosis and treatment of these neoplasms.

PMID- 12185908
TI  - [Parathyroid cyst. Report of one case].
AB  - Parathyroid cysts are rare in clinical practical. We report of 33 years old
      woman, with a cystic lesion in the right lobe of thyroid. The content of the cyst
      obtained through needle aspiration, showed a high PTH concentration
      (parathyroidhormone). The patient underwent surgery and the cyst was removed. The
      anatomopathological diagnosis was a parathyroid cyst.

PMID- 12185909
TI  - Variation of climatic and physical co-determinants of phytoplankton community in
      four nictemeral sampling days in a shallow tropical reservoir, southeastern
      Brazil.
AB  - Spatial and temporal variation of climatic and physical characteristics in a
      shallow tropical reservoir in the city of Sao Paulo, Southeastern Brazil, and
      their possible influence on the dynamics of the phytoplankton population. Samples
      were taken at 5 depths of the water column (subsurface: 1% Io, 10% Io, 2 m, and
      bottom) and at 4 hour intervals (6:00, 10:00, 14:00, 18:00, 22:00, 2:00, and 6:00
      h) during summer (March 3-4), fall (June 13-14), winter (August 29-30), and
      spring (November 29-30) of 1994 at a single sampling station. Garcas Reservoir
      (23 degrees 39'S, 46 degrees 37'W) is a kinetic turbulent system, highly
      influenced by winds, with stratification that may last for days or weeks, and
      which undergoes mixing periods more than once in a year. A thermal pattern of
      this type is comparable to the warm discontinuous polymetric. Considering its
      optical properties, the water body was classified as an ecosystem with moderate
      turbidity, which decreases basically due to increased phacopigment concentration
      during the spring. Also, the reservoir is an ecosystem whose phytoplanktonic
      community is subjected to stress, the degree of which depends on level of light
      penetration.

PMID- 12185911
TI  - Condition factor in nine species of fish of the Characidae family in the upper
      Parana River floodplain, Brazil.
AB  - The condition factor for nine species of tropical freshwater fish of the
      Characidae family in the upper Parana River floodplain is described. Fish were
      caught over a period of 12 months (February 1993 to March 1994). Knowledge of the
      nine species is important for adequate management and maintenance of the
      biological equilibrium of the ecosystem.

PMID- 12185910
TI  - Substrate use and selection in sympatric intertidal hermit crab species.
AB  - Coexisting hermit crabs may competitively interact for shells and microhabitats,
      mainly when shell availability is habitat-related. Three species of Clibanarius
      (C. antillensis, C. sclopetarius, and C. vittatus) coexist in the intertidal
      region of Pernambuco Islet, Araca Region, Sao Sebastiao Channel, southeastern
      Brazil. This study evaluated crab preferences for four substrate types used by
      these species in nature (rocky shore, pebbles, sand, and mud) in allopatric
      (single species) and sympatric (three species) treatments in simulations of high
      tide and low tide. The substrate preference of the three hermit crabs did not
      vary between low and high tide situations. At low tide the crabs either moved
      into holes in the highly complex rocky substrate or buried themselves in mud.
      Substrate selection may explain the patterns of substrate use in nature only for
      C. vittatus. Clibanarius antillensis and C. sclopetarius showed closer
      similarities in the pattern of substrate selection in the sympatric treatment
      with the substrate use in nature than in allopatric treatment, indicating a
      positive influence (dependence) of the presence of one species on the presence of
      another. Use of sub-optimal substrates, mainly by C. antillensis, may be caused
      by other factors such as its low desiccation tolerances. If competition for space
      takes place among these species, it would be more intense between C. sclopetarius
      and C. vittatus given their higher overlap in substrate preference than between
      them and C. antillensis.

PMID- 12185912
TI  - Cyclopidae (Crustacea, Copepoda) from the upper Parana River floodplain, Brazil.
AB  - Cyclopid copepods from samples of fauna associated with aquatic macrophytes and
      plancton obtained in lotic and lentic environments were obtained from the upper
      Parana River floodplain (in the states of Parana and Mato Grosso do Sul, Brazil).
      Macrophytes were collected in homogeneous stands and washed. Plankton samples,
      taken from the water column surface and bottom, were obtained using a motor pump,
      with a 70 microns mesh plankton net for filtration. Twelve taxa of Cyclopidae
      were identified. Among them, Macrocyclops albidus albidus, Paracyclops chiltoni,
      Ectocyclops rubescens, Homocyclops ater, Eucyclops solitarius, Mesocyclops
      longisetus curvatus, Mesocyclops ogunnus, and Microcyclops finitimus were new
      finds for this floodplain. Eight species were recorded exclusively in aquatic
      macrophyte samples. Among these species, M. albidus albidus and M. finitimus
      presented greatest abundances. Only four species were recorded in plankton
      samples, and Thermocyclops minutus and Thermocyclops decipiens are limited to
      this type of habitat. Among these four species, T. minutus is the most abundant,
      especially in lentic habitats.

PMID- 12185913
TI  - Comparative morphology of Astraea latispina (Philippi, 1844) and Astraea olfersii
      (Philippi, 1846) (Mollusca, Gastropoda, Turbinidae).
AB  - The present study examines comparatively the soft parts of turbinids Astraea
      latispina and Astraea olfersii. The characters of soft parts of these species, in
      agreement with Trochoidea organization, allow a differential diagnosis on the
      cefalic lappets, appendix of eye-stalk, hypobranchial glands, jaws, radulae, and
      stomach spiral caecum, which information will be helpful in taxonomic studies.

PMID- 12185914
TI  - Population dynamics of euglossinae bees (Hymenoptera, Apidae) in an early second
      growth forest of Cajual Island, in the state of Maranhao, Brazil.
AB  - A study was conducted in an early second-growth forest aiming at knowing the
      richness, relative abundance, seasonal distribution, and hourly frequency of
      euglossine bees, and their association with scent baits. Male bees were attracted
      to cineole, vanillin, methyl salicylate, and eugenol. The baits were hooked 1.5 m
      high and 6 m from one another. The specimens were collected from December 1997 to
      November 1998, once a month, from 7:00 to 17:00 h. A total of 339 male euglossine
      bees were caught, accounting for 19 species and four genera. The most common
      species was E. cordata, making up 69.9% of the individuals, followed by E.
      truncata (2.3%), E. violaceifrons, and E. smaragdina (2.1%). The most attractive
      scent was cineole, which baited 87% of the specimens and 73.7% of the species.
      Vanillin, the second most visited bait, eured 7.6% of the specimens and 26.3% of
      the species. E. surinamensis was only collected with this bait. Methyl salicylate
      and eugenol baited combined 2.6% of the specimens. However, by species numbers
      Methyl salicylate attracted 21% whereas eugenol was attractive for 15.8% of them.
      In general, the species were more abundantly found in the rainy season (January
      June). The hourly activity data showed that the euglossine bees were attracted to
      the baits all day long, but at a higher frequency in the morning period, peaking
      between 8:00 and 10:00 h.

PMID- 12185915
TI  - Butterflies from the Uberlandia region, central Brazil: species list and
      biological comments.
AB  - A total of 251 butterfly species were recorded in Uberlandia region, with
      collecting concentrated mainly in forest areas. Aspects of geographic
      distribution of some Ithomiinae, as well as interactions of both adults and
      immatures with plants, and reproduction periods for the more abundant species are
      discussed. Collections in open, riverside, and wetland areas, as well as the use
      of bait, should substantially increase the number of species.

PMID- 12185916
TI  - Fish stock assessment of piraputanga Brycon microlepis in the Cuiaba River Basin,
      Pantanal of Mato Grosso, Brazil.
AB  - Fork length measurements of individuals of Brycon microlepis landed and
      commercialized at the Porto Market in Cuiaba, MT, from May-October 1996 to May
      October 1997 were used to estimate growth and mortality parameters for this
      species. The average estimated populational parameters were: L infinity = 705 mm,
      k = 0.275 year-1, C = 0.775, WP = 0.465, Lc = 164 mm, M = 0.585 year-1, Z = 0.822
      year-1, with F = 0.237 year-1. Yield per recruit analysis suggests that the stock
      is not yet overexploited.

PMID- 12185917
TI  - Distribution pattern of two fish species in a coastal stream in southeast Brazil.
AB  - Longitudinal distribution of Mimagoniates microlepis and Hoplias malabaricus was
      analyzed in a coastal stream system in Southeast Brazil. Six sites were sampled
      by electrofishing in seven months, from July 94 to July 95. Densities of M.
      microlepis, and H. malabaricus and its prey (Poecilia vivipara, Deuterodon sp.
      and Astyanax janeiroensis) were estimated by the Zippin method; environmental
      variables of: (i) kind of substratum; (ii) percentage of pools, runs, riffles,
      instream vegetation, and canopy were registered for each site in each sampling
      month. The relative importance of each biotic and abiotic variable was tested
      through simple correlation analyses. We verified that M. microlepis occurrence
      correlates with canopy; H. malabaricus is correlated with instream vegetation,
      pools, clay substratum, and P. vivipara densities; and P. vivipara correlates
      with pools and clay substratum. Our results suggest that environmental variables,
      and food and shelter availability are the main factors in determining M.
      microlepis and H. malabaricus distribution.

PMID- 12185918
TI  - Morphology and anatomy of leaf mine in Richterago riparia Roque (Asteraceae) in
      the campos rupestres of Serra do Cipo, Brazil.
AB  - The leaf mine in Richterago riparia is caused by a lepidopteran larva
      (lepidopteronome). The leaves of R. riparia show campdodrome venation; the
      epidermis is unistratified, with stomata and glandular trichomes in adaxial and
      abaxial surfaces. The mesophyll is bilateral and the vascular system is
      collateral. During the formation of the mine, the larva consumes the chlorenchyma
      of the mesophyll and the smaller vascular bundles (veins of third and fourth
      orders). Structural alterations in the tissues of the host plant were not
      observed, except for the formation of a wound meristem and the presence of cells
      with phenolic substances next to the mine. Three cephalic exuviae of the miner
      were found in the mesophyll. This lepidopteronome is parenchymatic and the
      epidermis remains intact, but forms a protective layer for the mining insect.

PMID- 12185919
TI  - Development of a chamber for in situ toxicity tests with small fishes.

PMID- 12185920
TI  - Birth and mortality of maned wolves Chrysocyon brachyurus (Illiger, 1811) in
      captivity.
AB  - The aims of this study were to verify the distribution of births of captive maned
      wolves Chrysocyon brachyurus and the causes of their deaths during the period
      from 1980 to 1998, based on the registry of births and deaths in the
      International Studbook for Maned Wolves. To determine birth distribution and
      average litter size, 361 parturitions were analyzed for the 1989-98 period. To
      analyze causes of mortality, the animals were divided into four groups: 1. pups
      born in captivity that died prior to one year of age; 2. animals born in
      captivity that died at more than one year of age; 3. animals captured in the wild
      that died at any age; and 4. all animals that died during the 1980-98 period. In
      group 1, the main causes of mortality were parental incompetence (67%),
      infectious diseases, (9%) and digestive system disorders (5%). The average
      mortality rate for pups was 56%. Parental incompetence was responsible for 95% of
      pup deaths during the first week of life. In group 2, the main causes were
      euthanasia (18%) and disorders of the genitourinary (10%) and digestive systems
      (8%). Euthanasia was implemented due to senility, congenital disorders,
      degenerative diseases, and trauma. In group 3, the main causes were digestive
      system disorders (12%), infectious diseases (10%), and lesions or accidents
      (10%). The main causes of mortality of maned wolves in captivity (group 4) were
      parental incompetence (38%), infectious diseases (9%), and digestive system
      disorders (7%).

PMID- 12185921
TI  - Feeding preferences of the endemic gastropod Astraea latispina in relation to
      chemical defenses of Brazilian tropical seaweeds.
AB  - Seaweed preference by the Brazilian endemic gastropod Astraea latispina was
      examined in the laboratory to evaluate the role of secondary metabolites in
      determining food choice. Of three species of seaweeds examined, Plocamium
      brasiliense was highly preferred; less so were Sargassum furcatum and Dictyota
      cervicornis were preferred less. Extracts and/or pure major metabolites of the
      two potentially chemically-defended seaweeds (P. brasiliense and D. cervicornis)
      were tested as feeding deterrents against A. latispina. Algal extract assays
      demonstrated that three concentrations of crude organic extract of the red alga
      P. brasiliense (50%, 100%: natural concentration, and 200% of dry weight: dw) did
      not affect feeding of this gastropod. In contrast, the three concentrations of
      crude organic extract of the brown alga D. cervicornis (50%, 100% and 200% dw)
      inhibited feeding by A. latispina. The chemical deterrent property of D.
      cervicornis extract against the gastropod A. latispina occurred due to a mixture
      of the secodolastane diterpenes isolinearol/linearol (4:1--0.08% dry weight).
      This is the first report showing that Dictyota cervicornis produces a chemical
      defense against herbivores using secodolastane diterpenoid. In addition, these
      results widen the action spectrum of secondary metabolites found in seaweed
      belonging to this brown algal genus.

PMID- 12185922
TI  - Early life stages of fish and the relationships with zooplankton in a tropical
      Brazilian reservoir: Lake Monte Alegre.
AB  - For evaluating the trophic relationship between early life stages of fish and
      zooplankton in Lake Monte Alegre, fish distribution and feeding habits have been
      studied in areas with and without macrophytes. In the first of these areas, 356
      specimens belonging to 8 species, mostly juveniles, were caught by a sieve.
      Another 35 specimens, belonging to 4 species, were caught by gill nets and seine
      in areas lacking macrophytes. Their diets were composed of aquatic insects,
      microcrustaceans, rotifers, detritus, and other aquatic invertebrates.
      Microcrustacean prey were mainly littoral or benthic dwellers, found in the
      highest proportion in specimens of 7-20 mm SL. Most fish species have parental
      care, which could explain the absence of planktonic larvae. Early life stages of
      fish do not exert a predation pressure on the lake zooplankton.

PMID- 12185923
TI  - Sand bar opening in a coastal lagoon (Iquipari) in the northern region of Rio De
      Janeiro State: hydrological and hydrochemical changes.
AB  - The aim of this paper was to verify hydrological and hydrochemical changes in the
      Iquipari Lagoon water column, during three months, as related to an artificial
      sand bar opening. A drastic reduction in water volume occurred 28 hours after the
      sand bar opening, exposing the bottom sediment. This was densely colonized by
      submerged aquatic plants, which were dominant in the ecosystem metabolism,
      specially near the sand bar. An increase in salinity values, and dissolved and
      total nutrient concentrations, was observed during the sand bar opening period.
      In contrast, chlorophyll a concentration decreased. These changes were associated
      with: 1) mix of remained brackish and marine waters; 2) nutrient release from
      sediments by physical processes; and 3) submerged plant death. After the sand bar
      closure, lagoon metabolism was completely regulated by a dense phytoplankton
      community. We observed that the sand bar opening resulted in an extensile
      replacement of the lagoon's water and a change in the community mainly
      responsible for the ecosystem metabolism.

PMID- 12185924
TI  - The influence of Eucalyptus plantations on the macrofauna associated with
      Salvinia auriculata in southeast Brazil.
AB  - The influence of Eucalyptus plantations on the structure and composition of
      macroinvertebrate communities associated with the aquatic fern Salvinia
      auriculata Aublet were investigated in a high altitude lake bordered by either
      secondary Atlantic forest or Eucalyptus plantations. Comparisons of the diversity
      of Chironomidae (Diptera, Insecta) larvae in the littoral zone between these two
      vegetation types showed higher diversity of larvae in waters bordered by
      Eucalyptus. The results demonstrated that the predominance of carnivorous taxa
      among the macroinvertebrate fauna appears to be the major controlling factor for
      limiting diversity in lake areas bordered by Eucalyptus.

PMID- 12185925
TI  - Distribution, survivorship and mortality sources in immature stages of the
      neotropical leaf miner Pachyschelus coeruleipennis Kerremans (Coleoptera:
      Buprestidae).
AB  - Distribution, sources of mortality, and survivorship of immatures was
      investigated during the reproductive season of the neotropical buprestid leaf
      miner, Pachyschelus coeruleipennis, that burrows in leaves of Croton floribundus
      (Euphorbiaceae) in SE, Brazil. Immature distribution was investigated by a random
      sample of 120 shrubs of C. floribundus growing along forest edges. Marked leaves
      were followed to recorded sources of mortality and survivorship of immature
      stages. Females lay their eggs preferentially in the young leaves of the host
      plant, with mines and pupal cells having been found on the middle part of plants.
      Densities of eggs, active mines, and pupal cells were, respectively, 25 +/- 2, 6
      +/- 1, and 1 +/- 0.3 per 100 leaves. Predators and parasitoids accounted for the
      majority of losses in the immature P. coeruleipennis population. Mortality was 3
      times lower in the egg stage than in the last larval instar. Predation rate was
      greater than parasitism but the latter increased much more during the development
      of immatures. Survivorship and sources of mortality were different between early
      and late season sample of leaf-miner immatures. Parasitism rate was greater in
      the late-season whereas predation was greater in early-season samples. These
      results are compared with mortality patterns described for other buprestid leaf
      miners in temperate and tropical regions.

PMID- 12185926
TI  - Diversity and biomass of chironomidae (Diptera) larvae in an impacted coastal
      lagoon in Rio De Janeiro, Brazil.
AB  - Diversity and biomass of Chironomidae larvae were studied between January
      November 1993 and March-November 1994 in an impacted lagoon in Rio de Janeiro,
      Southeastern Brazil, in an attempt to establish the ecological consequences of
      anthropogenic eutrophication processes. Nine hundred and seventy-five organisms
      belonging to the Tanypodinae, Orthocladiinae, and Chironominae were collected.
      Polypedilum (62%) and Chironomus (58%) were the most common genera found in the
      limnetic and littoral zones.

PMID- 12185927
TI  - Variation of biometric parameters and C, N, and P concentrations of Oryza
      glumaepatula at different depths of an Amazonian lake impacted by bauxite
      tailings (Lake Batata, Para, Brazil).
AB  - Lake Batata is a typical Amazonian clear water lake which has undergone
      anthropogenic impacts. Thirty percent of its total area has been covered with
      bauxite tailings. Thus, it is possible to distinguish two areas in this
      ecosystem: the impacted and the natural. The goal of this research was to study
      C, N, and P content variation and the values of biomass, length, density, and
      culm diameter of Oryza glumaepatula at different depths in the natural and
      impacted areas of Lake Batata. The results obtained in this research suggest that
      the availability of P and N, in both water and sediment, is lower at the shallow
      site when compared to the deeper sites. On the other hand, C concentrations
      decreased as P and N concentrations increased. This may be explained by the
      structural function of C in aquatic macrophytes. At shallower sites, due to the
      reduced water column, individuals invest in supporting structures that display
      high C concentrations. The higher density and biomass of O. glumaepatula at the
      intermediate site indicate that this area presents the best conditions for
      germination and establishment of individuals of this species. The chemical
      composition and biometric parameters of O. glumaepatula have shown that this
      population has higher spatial variation in the natural area. In the impacted
      area, the absence of significant variations in N and P concentrations in O.
      glumaepatula among the three sampled sites promotes higher homogeneity in the
      stands. The high C:P and N:P ratios indicate that, in the impacted area, P is
      more limiting to the development of O. glumaepatula than it is in the natural
      area. The reduced values of biomass and density of O. glumaepatula in the
      impacted area suggest that the bauxite tailings limit the development of this
      population.

PMID- 12185928
TI  - Life cycle, feeding and adaptive strategy implications on the co-occurrence of
      Argyrodiaptomus furcatus and Notodiaptomus iheringi in Lobo-Broa reservoir (SP,
      Brazil).
AB  - The population dynamics, life cycle and feeding of Argyrodiaptomus furcatus and
      Notodiaptomus iheringi, were studied in Broa reservoir from August 1988 to August
      1989, period when a replacement of A. furcatus by N. iheringi was observed. Some
      abiotic factors such as temperature, dissolved oxygen, pH and conductivity were
      measured to characterize the limnological conditions of the reservoir. Also,
      phytoplankton composition was analyzed and related to the feeding of the two
      species. Experimental data on developmental time and reproduction of A. furcatus
      and N. iheringi under different temperatures showed that lower temperatures were
      responsible for density decreasing of both populations in the reservoir during
      the dry season. Chlorophyta and Chrysophyta smaller than 20 microns were the most
      abundant phytoplankton groups in the reservoir as well as in the gut content of
      A. furcatus and N. iheringi, representing an important food source for both
      species. The temporary disappearance of Argyrodiaptomus furcatus, observed
      between 1988 and 1989 and its replacement by Notodiaptomus iheringi was related
      to mining activities upstream, modifying the water turbidity, pH and
      conductivity. However, the reappearance and maintenance of A. furcatus for
      another ten years and a recent replacement re-incidence indicates that these two
      calanoids do not coexist in this environment. Adaptive strategies of both
      species, related to changes in environmental conditions, are discussed. Probably,
      Argyrodiaptomus furcatus is an indicator of less eutrophic environments, while
      Notodiaptomus iheringi of more eutrophic systems.

PMID- 12185929
TI  - GORD and Barrett's oesophagus: does oesophageal motility matter?

PMID- 12185930
TI  - Barrett's esophagus control after antireflux surgery.
AB  - OBJECTIVE: To study the esophageal motor disorders in patients with Barrett's
      esophagus after surgical treatment. DESIGN: From January 1993 to September 1998 a
      prospective study with 25 patients referred to our service for surgical treatment
      of Barrett's esophagus was conducted. Barium transit, endoscopy, 24-hour
      monitoring of intraluminal pH and stationary esophageal manometry were carried
      out in all patients pre- and postoperatively. The results were compared before
      and after surgery. A p < 0.05 was considered statistically significant. PATIENTS:
      18 male (72%) and 7 women (28%). Mean age was 54.20 +/- 13.29 years (range: 25-71
      years). The most frequent clinical manifestation was heartburn (92%). A
      laparotomy procedure was performed in 68% (n = 17) and laparoscopy in 32% (n = 8)
      of patients. A 360 degrees fundoplication was always performed. RESULTS: 96% of
      patients presented a defective lower esophageal sphincter. The statistical study
      demonstrated significant differences after surgery for all pH-metric parameters
      and lower esophageal sphincter (p < 0.01), except for relaxation (p = 0.465). In
      the esophageal body, the statistical study only demonstrated significant
      differences for mean pressure of the peristaltic waves in segment I (p = 0.038)
      and mean rate of non-transmitted waves in esophageal segment IV-V (p = 0.031).
      CONCLUSIONS: Antireflux surgery in Barrett's esophagus contributes to the control
      of gastroesophageal reflux improving esophageal clearing and with significant
      differences for the mean rate of non-transmitted waves in the distal esophagus.

PMID- 12185931
TI  - Colonic volvulus.
AB  - OBJECTIVE: To review the incidence of volvulations in our workplace, to study the
      procedures employed in its treatment, and to discuss our results during the last
      20 years. MATERIAL AND METHODS: A series of colonic volvulus treated between 1978
      and 1998 at one hospital is presented. RESULTS: We reviewed 41 cases. Volvulus
      locations are: sigmoid colon: 21, caecum: 17, transverse colon: 2, and splenic
      flexure: 1. Mortality rates according to the type of volvulus and type of
      operative procedure is analyzed. Four cases of volvulus recurrence (9%).
      CONCLUSIONS: Treatment guidelines for the approach to colonic volvulus are
      presented.

PMID- 12185932
TI  - Which is the best distension protocol to study rectal sensitivity in the
      irritable bowel syndrome?
AB  - OBJECTIVE: To evaluate any differences in rectal distension perception between
      healthy subjects and patients with irritable bowel syndrome (IBS) according to an
      isobaric distension protocol (progressive or phasic). MATERIAL AND METHODS: 10
      healthy subjects and 41 patients with IBS (Rome II criteria). Rectal distension
      was performed using a barostat connected to a 500 mL bag, and a progressive
      distension protocol (continuous distension at a rate of 0.36 mmHg/sec) was
      compared to phasic distension protocol (distensions for 60 sec with 4 mmHg
      increases separated by 0 mmHg pressures during 60 sec). Perception was evaluated
      using three descriptive scales of 7 categories each for perception type,
      intensity, and affectivity. Perception thresholds were assessed. RESULTS: No
      significant differences in any perception thresholds were found between control
      subjects and IBS patients using a progressive distension protocol. Differences in
      the perception of inconvenient distension and maximum tolerable distension were
      encountered with the phasic distension protocol. Uncomfortable distension
      thresholds below those of controls were found in 48.8% of patients with IBS when
      a phasic distension protocol was used, versus only 9.7% with a progressive
      protocol. CONCLUSION: Hypersensitivity in patients with IBS is mainly seen with
      the use of phasic distension isobaric protocols for affective negative
      perceptions.

PMID- 12185933
TI  - Strangulated volvulus of the sigmoid colon with inviable mucosal appearance in a
      non-surgical patient. Endoscopic devolvulation.
AB  - Colonoscopy is presently always performed before surgical management of a
      volvulus in the sigmoid colon. It leads to know the viability of the mucosa and,
      when possible, to resolve the volvulus conservatively. Besides, with endoscopic
      control, we can place a decompression tube proximal to the volvulated sigmoid
      colon, favouring a non-surgical resolution. With this conservative approach it is
      possible to overcome the acute period, and to restore the viability of the
      sigmoid wall, waiting for a definitive surgical management with less morbidity
      and mortality. Only with endoscopy, revolvulation does occur in 35-50% of cases.
      We present the clinical case of a sigmoid volvulus with compromised sigmoid wall
      in an 82-year-old man with several clinical problems contraindicating surgery.
      Endoscopic devolvulation with tube placement was adequate to resolve this sigmoid
      volvulus.

PMID- 12185934
TI  - [Ascites as initial manifestation of primary hypothyroidism].

PMID- 12185935
TI  - [Wilson's disease and pregnancy].

PMID- 12185936
TI  - [Eosinophilic ileitis: an infrequent cause of intestinal obstruction].

PMID- 12185937
TI  - [Acute appendicitis in strangulated crural hernia. A variant of Amyand's hernia].

PMID- 12185938
TI  - [Intestinal pseudo-obstruction in Steinert's disease].

PMID- 12185939
TI  - [What is your diagnosis? Tuberous sclerosis (Bourneville-Pringle syndrome)].

PMID- 12185940
TI  - [Geneva-Lausanne laboratory for presurgical epilepsy diagnosis: experiences with
      the first 150 patients].
AB  - In Switzerland there are approximately 35,000 to 70,000 patients who suffer from
      epilepsy. In 20% of these patients, seizures cannot be satisfactorily suppressed
      by medical treatment (so-called pharmacoresistent epilepsy); thus surgical
      therapy represents an alternative. We report on the first 150 patients who have
      been investigated in the presurgical epilepsy laboratory Geneva-Lausanne since
      its foundation in April 1995. Of these patients, 75% were adults and 25% were
      adolescents or infants. In 87% of all patients, non-invasive methods (phase I)
      were sufficient for diagnosis. In our laboratory, these methods encompassed the
      following techniques: prolonged video-EEG monitoring, high resolution MRI,
      positron-emission-tomography (PET), and neurological and neuropsychological exams
      during the interictal and postictal periods. In 13% of cases, the epileptic focus
      was localized by intracranial electrodes as well as differentiated against vital
      cortex (phase II). Of all operated patients, 78% were seizure-free post
      operatively, and another 14% significantly ameliorated, such that more than 90%
      significantly benefited from the intervention. Psychosocial variables
      (professional, social integration) as changes were also analysed post
      operatively. Although the majority of the patients were seizure-free, only 1/4 to
      1/3 of all patients showed an improvement in their psychosocial situation. This
      is most likely due to the long delay between the onset of epilepsy and surgical
      treatment, which was found to be approximately 10 to 40 years in our patient
      population. The necessity to pose the diagnosis "pharmacoresistant epilepsy" as
      fast as possible is discussed, in order to shorten the delay to a few years until
      a possible operation.

PMID- 12185941
TI  - [Radiological diagnosis of lung embolism].

PMID- 12185942
TI  - [Palpation of the male breast: a diagnostic dilemma].

PMID- 12185943
TI  - [Kaposi sarcoma in HIV infection].

PMID- 12185944
TI  - [Common backache of unusual etiology].

PMID- 12185945
TI  - [Sexually transmitted diseases and health policy in Germany in the 19th and early
      20th century. II. Pragmatism and surveillance].

PMID- 12185946
TI  - [Significance of physical training on prevention in elderly patients].
AB  - The loss of strength, coordination, endurance, and flexibility with increasing
      age is only partly due to the aging process itself. A major factor is physical
      activity, i.e. the influence of implicit or explicit training stimuli. All
      elements of physical performance can be improved through training even in the
      very old, if the intensity and frequency of training are adequate. For the
      elderly, strength and coordination are particularly important elements of
      training since they constitute a prerequisite for an independent way of living.
      To minimize the cardiovascular risks during strength training, we developed and
      tested a new method which leads to significantly smaller increases in blood
      pressure than conventional approaches.

PMID- 12185947
TI  - [Malnutrition in elderly patients].
AB  - Malnutrition in older patients is associated with significantly higher morbidity
      and mortality, this incurring substantial extra costs in health care. However,
      impaired nutritional status is recognized only in a small number of cases and
      treated adequately. This emphasizes the need for integrating nutritional
      questions into the overall therapeutical concept. This may decrease the incidence
      and progression of geriatric illnesses. The sooner such interventions are
      introduced, the better.

PMID- 12185948
TI  - [Significance of arterial hypertension in geriatric prevention].
AB  - In Germany for decades the assessment and treatment of patients with high blood
      pressure is not satisfactory. As in other industrial countries only approximately
      50% of hypertensive men and 60% of hypertensive women are diagnosed. Arterial
      hypertension bears the known risks on heart and vascular system also in old age
      when often target organ damages are already present. A sufficient number of
      clinical studies proves risk reduction by blood pressure lowering treatment.
      According to the criteria of WHO in old age the same limits of normal blood
      pressure and the same stages of the disease are valid as in younger patients. The
      probability of cardiovascular complications increases with the height of blood
      pressure. As small increases of blood pressure are far more prevalent than very
      high blood pressure values the cumulative risk in populations is predominantly
      linked to mild hypertension. In elderly patients systolic blood pressure has a
      better predictive value than diastolic blood pressure. A short review is given of
      work up and treatment of hypertension in the elderly instructed by the Guidelines
      of the German Hypertension Society.

PMID- 12185949
TI  - [Primary and secondary prevention in dyslipidemia in the elderly].
AB  - Cardiovascular disease (CVD) is the leading cause of mortality and a major cause
      of disability in advanced age. The relationship between coronary heart disease
      (CHD) and dyslipoproteinaemia is well known. The fact, however, that
      atherosclerosis is a systemic disease leads also to the consideration that
      patients suffering from cerebrovascular and peripheral arterial disease should
      benefit similarly from lipid lowering therapy as do patients with CHD. There is
      already growing evidence that the incidence of stroke may be markedly decreased
      by statin therapy. Though overall, the clinical significance of
      hypercholesterolaemia seems to decrease with increasing age, patients at age 65
      to 75 tend to benefit even more than younger patients when elevated LDL
      cholesterol is treated effectively. It should be noticed that prevention or
      postponement of cardiovascular events may also prevent premature functional
      limitations and disability in old age. Hence, it is suggested to screen elderly
      people with CVD for dyslipoproteinaemia and to treat elevated cholesterol levels
      by means of life style changes, nutritional therapy, and drug therapy. Treatment
      regimes should be considered depending upon complete risk stratification and
      geriatric assessment. Chronological age alone cannot be an argument to withhold a
      proven effective therapy from a growing segment of the population at risk.

PMID- 12185950
TI  - [Osteoporosis in elderly patients].
AB  - Osteoporosis is defined by an abnormal high loss of bone mineral. This loss leads
      to fractures of vertebral bodies as of the femoral neck with dramatic
      consequences. Therefore it is necessary to regard osteoporosis as a disease
      rather than normal aging process. Diagnosis of osteoporosis is based on clinical
      examination and measurement of bone-mineral density. Beyond life-style changing
      interventions pharmacological treatment in a stepwise approach is recommended.
      Supplementation with Vitamin D and calcium is the mainstay of therapy with
      individual addition of bisphosphonates or other substances. The specific ways for
      decision making are exemplified with special regard to their individual
      advantages and disadvantages.

PMID- 12185951
TI  - [Diagnosis of the risk of accidental falls in the elderly].
AB  - The steep increase in the incidence of hip fractures and other fall-related
      fractures with advancing age is caused by an age-associated combination of
      increased fall frequency, typical fall mechanisms and reduced bone strength. This
      article reviews the current knowledge related to fall risk factors and fall
      mechanisms. Non-syncopal falls during normal daily activities are predominantly
      age-associated occurrences with serious consequences. 5% of all falls cause
      fractures, another 10 to 15% lead to a variety of further injuries. The most
      serious consequences of the geriatric fall syndrome are fractures of hip,
      humerus, wrist and pelvis. Fear of falling and self limitation of physical
      activity are self imposed psychological impairments. There is a pathological
      cascade from age-associated gait and balance disorders to locomotor falls and
      further to fall-related fractures. Significantly increased fall risk caused by
      gait and balance disorders can be considered as a distinct chronic pathological
      condition. It is strongly age-related and definitely has a multifactorial origin.
      The term "age-associated multifactorial gait disorder" has been coined for this
      condition. Assessing fracture risk requires evaluating fall risk, fall mechanisms
      and bone strength. Older people with gait and balance disorders fall mostly
      sideways, and the impact of such a fall from standing height generates enough
      force to break an older non-osteoporotic femur. Osteoporosis can decrease bone
      strength beyond the age-related grade, and is one of the several most important
      risk factors for fractures. Prospective studies have consistently found the
      following independent risk factors for non-syncopal falls: 1. Muscle power of
      lower extremities, 2. Lateral postural stability, 3. Clinical evaluation of gait,
      4. Visual impairment, 5. Four or more different medications or certain
      psychotropic drugs, 6. Cognitive impairment, and 7. History of falling. The fall
      related neuromuscular status can be adequately assessed by three diagnostic
      procedures: The chair rising test represents muscle power, and has proven its
      relevance for both fall risk and deterioration of mobility and functional
      independence. Measurement of lateral postural stability can be done by tandem
      manoeuvres. Clinical evaluation of gait should focus on the regularity of gait as
      a cyclic event. The fall risk status of an individual depends strongly on the
      number of the independent risk factors that one accumulates. Both prevention and
      therapy must focus on each of these individual risk factors. Preventing falls and
      its consequences is imperative for successful aging.

PMID- 12185952
TI  - [Hip protectors in prevention of proximal femoral fracture].
AB  - Hip fractures are a major cause of impairment, disability and death in elderly
      people. The incidence of hip fractures is increasing. Most attempts to prevent
      hip fractures have focused on reducing underlying medical disorders and risk. In
      1993 Lauritzen et al. reported the results of a clinical trial which showed a
      significant (53%) reduction for hip fractures in the protector wearing group.
      These results were reproduced many times. Hip protectors offer a powerful new
      method for reducing the risk of hip fractures. Their use should be encouraged for
      people with advanced osteoporosis or high fall risk and for those living in
      nursing homes.

PMID- 12185953
TI  - [Detection and treatment of depressive symptoms in nursing home patients. An
      interdisciplinary challenge for the geriatric physician and nursing personnel].
AB  - 40% of nursing home patients have depressive symptoms and 20% have a diagnosis of
      depression according to DSM-IV or ICD-10 classification. Depressive Symptoms in
      nursing home patients are underdiagnosed and undertreated. We report a triple
      pharmacological, psychosocial and staff teaching intervention in a nursing home
      based on the Resident Assessment Protocols (RAP) trigger mechanism of the
      Resident Assessment Instrument (RAI) that was able to significantly and
      persistently reduce the prevalence of depressive symptoms in this population.

PMID- 12185954
TI  - [Growth hormone and prevention in elderly patients--fantasy and reality].
AB  - Human growth hormone is one of the hormones used most frequently in the setting
      of so-called anti-aging strategies. To date, the preventive value of such a
      hormone replacement therapy in relatively healthy and well functioning middle
      aged persons is unknown. Although growth hormone leads to significant alterations
      in body composition and changes in serum cholesterol levels in patients with
      adult growth hormone deficiency, there are currently no data supporting the
      hypothesis that growth-hormone in non deficient persons prolongs life span or
      reduces morbidity. Aging is associated with a reduction of GH-secretion, serum
      levels of insulin like growth factor I (IGF-I) and alterations in body
      composition and function. Based on the many clinical similarities between aging
      and acquired growth hormone deficiency, several studies have assessed the effects
      of growth hormone administration in healthy aged women and men. Only a few
      studies have addressed functional outcomes in a more frail population. These
      studies suggest that a defined group of older individuals with functional
      limitation might benefit from GH as a strategy to prevent further functional
      decline and delay nursing home admission. Because of the lack of proof in frail
      patients, uncertain long-term effects and high treatment costs GH-administration
      in the aged should currently be restricted to research questions. Future studies
      should address the question whether growth hormone alone or in combination with
      established strategies, such as exercise or improvement in nutrition will serve
      as a measure to prevent functional decline in frail geriatric patient
      populations.

PMID- 12185955
TI  - [Regulatory status of safety pharmacology. Implications].
AB  - Safety Pharmacology is now specified by various European and international
      guidelines. The ICHS7A text, which has now been implemented, requires all new
      compounds to be tested before any administration in humans. The compound should
      be evaluated under GLPs for its potential effects on so-called vital functions
      (cardio-vascular, respiratory and central nervous system). Also, the potential
      risk for QT prolongation and Torsades de Pointes should be appropriately assessed
      using in vitro and in vivo models (CPMP/986/96 and draft ICHS7B) before the
      initiation of Phase I. Various other European or international guidelines relate
      to more specific evaluations: abuse liability, anti-osteoporotic compounds, etc.
      Safety Pharmacology should also, as other studies required for regulatory
      submission, be conform to the electronic records and signature constraints (CFR23
      part 11 for the USA) and to the format of the Common Technical Document (ICHM4).
      To address all these requirements, the pharmaceutical industry should now be
      creating specially assigned Safety Pharmacology teams.

PMID- 12185956
TI  - Preclinical testing for teratogenicity and developmental toxicity: methods and
      limitations.
AB  - With regard to the risk of reproductive or developmental toxicity, the regulatory
      decisions to allow clinical trials in humans or the marketing of a new drug are
      based almost entirely on animal data. This is not the case for other types of
      toxicity for which the preclinical data are supported by data from clinical
      trials. Whilst animal studies have been remarkably successful in the detection of
      reproductive toxicology over the last 40 years, they are not infallible. The
      efficacy of animal experimentation is largely dependent on the selection of
      appropriate animal models. Progress in the study of teratogenic mechanisms,
      comparative physiology, developmental biology and pharmacokinetics will hopefully
      continue to bring about more economical and effective uses of animals.
      Nevertheless, owing to the limitations of animal models, the monitoring of human
      births unfortunately remains an essential defence in the detection and early
      prevention of chemical-induced birth defects.

PMID- 12185957
TI  - Use of analgesics in self-medication.
AB  - Self-medication with analgesics is common and accepted and even recommended by
      health systems in order to avoid reimbursement. Self-medication, nevertheless, is
      not an easy task, since making choices is difficult for patients on the basis of
      the available standard information. Guiding information for patients has to be
      improved, but also physicians need to be trained how to handle self-medication of
      their patients. Special attention should be paid to the approval of combination
      analgesics for the treatment of headache and migraine. There were two major
      points of discussion during the last decades: possible risks of nephropathy and
      possible drug-induced overuse. According to a very recent evaluation, analgesic
      associated nephropathy appears to have been primarily caused by phenacetin rather
      than any other single or combination analgesics. Analgesic-induced overuse is
      also caused by the psychotropic actions of phenacetin in presentations providing
      rapid absorption, such as powders, rather than by other analgesics or caffeine.

PMID- 12185958
TI  - The use of vitamin supplements in self-medication.
AB  - Supplements, frequently containing vitamins, are often taken to try to compensate
      for an unhealthy life style or in an attempt to maximise health or performance.
      As illustrated by vitamin E, fundamental issues on both the efficacy and safety
      of the chronic use of relatively high dosages of vitamins still need to be
      resolved. To recommend the application of vitamin supplements, firstly the gaps
      in our knowledge on these fundamental issues should be filled. Secondly,
      objective and scientifically sound information should be given to the public. Via
      diverse sources there is an uncontrolled supply of vitamins. Educating the
      consumer on vitamins is therefore the only way to come to a rational use of
      vitamin supplements in self medication.

PMID- 12185959
TI  - [What are the prospects for pharmacological treatment of prion disease?].
AB  - There is currently no effective therapy available for Creutz-feldt-Jakob disease.
      However, a limited number of drugs such as polyanions, the amyloid-binding dye
      Congo red, amphotericin B anthracyclines, dapsone, beta sheet breaker peptides,
      porphyrines and phtalocyanines have been found to delay the appearance of the
      clinical signs in experimental prion diseases. Today, the most promising agent
      would appear to be a less toxic derivative of amphotericin B, MS-8209. Indeed
      this compound has a wide spectrum of anti-prion activity and is the only molecule
      capable of prolonging survival time when treatment is performed in the late
      stages of infection. This result represents an important step forward in
      therapeutical approaches of prion diseases and justifies the development of new
      polyene antibiotic derivatives.

PMID- 12185960
TI  - Sirolimus: has it gained from experience with older drugs?
AB  - The immunosuppressive drug sirolimus, recently licensed in Europe for use
      following kidney transplantation, was developed against a background in which it
      was common practice to use blood concentration measurements as a guide to
      therapy. This article sets out to document the use of blood concentration
      measurements in the assessment of the early and pivotal clinical trials of the
      drug and the attention that has been paid to the validation of analytical
      techniques used to measure the drug. It is concluded that, building on experience
      from the older drugs used for immunosuppression, data relating drug
      concentrations with efficacy outcomes have played a significant role in
      formulating guidelines on sirolimus dosing.

PMID- 12185961
TI  - Therapeutic drug monitoring of tacrolimus: a moving matter.
AB  - Tacrolimus is a calcineurin inhibitor immunosuppressant that has been widely used
      in the last decade. The recommended doses and therapeutic ranges have changed
      from the beginning because now new combinations of immunosuppressants are used
      and the tendency is to maintain low tacrolimus levels in order to avoid
      undesirable side effects. As there is a great pharmacokinetic variability between
      patients we have a pediatric liver transplant protocol to calculate the area
      under the curve (AUC) in order to avoid over-immunosuppression in patients with
      risk of lymphoproliferative disorder. We have studied the influence of hepatitis
      C virus infection (HCV) on tacrolimus requirements in patients with kidney
      transplant, and we observed that HCV+ patients need lower tacrolimus doses to
      maintain the same level as HCV-patients. These studies clearly contribute to
      improving drug effectiveness and thus to achieving an adequate immunosuppressive
      therapy.

PMID- 12185962
TI  - New drugs derived from medicinal plants.
AB  - In China, increasing emphasis has been laid in recent years on research on
      natural products. About 140 new drugs have been developed from Chinese medicinal
      plants. For example, anisodamine possesses good effects in the treatment of
      septic shock and morphine addiction; 3-n-butylphthalide isolated from seeds of
      celery was shown to be a new cerebral anti-ischemic agent; indirubin was
      identified as an anti-leukemic drug with no inhibition of bone marrow; huperzine
      is a potent and reversible inhibitor of acetylcholinesterase (AChE) and its
      selective action is superior to that of donepezil; clausenamide was shown to be a
      potassium channel blocker, its nootropic effect was 50-100 times more potent than
      that of piracetam; bicyclol was synthesized from schizandrin C isolated from
      Fructus schizandrae. It has remarkable hepatoprotective and certain anti
      hepatitis virus actions; salvianolic acid B is a very strong antioxidant agent
      with potential anti-dementia effects; yingzhaosu A and artemisinin are anti
      malaria drugs containing a peroxide ring which is very rarely seen in natural
      substances.

PMID- 12185963
TI  - [Leukotrienes and 12-HETE: key mediators of angiotensin II-mediated vascular
      effects.Rol in hypertension].
AB  - Arachidonic acid metabolism-derived products are key mediators of angiotensin II
      mediated vascular effects. The modulatory effect of cyclooxygenase derived
      products--in particular thromboxane A2 and prostaglandin H2--in angiotensin II
      mediated vascular effects is well established. In contrast, few studies have
      assessed the involvement of lipoxygenase-derived products in the vascular effects
      of angiotensin II. Cysteinyl leukotrienes (5-lipoxygenase-derived products) and
      12-hydroxyeicosatetraenoic acids (12-HETE) (12-lipoxygenase-derived products) are
      potent proinflammatory and vasomotor mediators. Their biosynthesis is increased
      in various models of hypertension. In addition, compelling evidence has suggested
      that they might contribute to the vasoconstrictor, hypertrophic and mitogenic
      effects of angiotensin II. The demonstration of their contribution to angiotensin
      II-mediated vascular effects may explain, at least in part, the vascular
      inflammatory complications associated with hypertension.

PMID- 12185964
TI  - [Effects of nitric oxide on cardioprotection prior to ischemia-reperfusion].
AB  - This study aimed at evaluating the role of nitric oxide (NO) when generated 24 h
      prior to ischemia-reperfusion. Three groups were studied in an isolated buffer
      perfused heart model: Control (saline = 3.3 mL/kg, n = 10), the precursor of NO,
      L-arginine, (500 mg/kg, n = 10) and an inhibitor of NO synthase, L-NAME, (10
      mg/kg, n = 9). All groups were injected intraperitoneally 24 h before heart
      extraction. Nitrites, nitrates (an index of nitric oxide release) and cardiac
      troponine I were assayed. During the reperfusion period, there was a low release
      of nitric oxide and cardiac troponine I associated with improved recovery of post
      ischemic myocardial function. These results indicate that in this model, the pre
      treatment improved myocardial function and thus, NO could play a role as a
      trigger and not as a mediator of cardioprotection.

PMID- 12185965
TI  - Type 4 phosphodiesterase-dependent pathways: role in inflammatory processes.
AB  - Type 4 phosphodiesterases (PDE4) belong to a superfamily of at least 11 isozymes
      catalyzing the hydrolysis of cyclic AMP (cAMP) and/or cyclic GMP (cGMP). PDE4
      regulate intracellular levels of cAMP and are the predominant PDE expressed in
      inflammatory cells. Elevation of cAMP produces the inhibition of different
      inflammatory processes, such as cellular trafficking, cytokine release or
      reactive oxygen species production. But recent papers showed that the involvement
      of PDE4 in inflammatory mechanisms cannot be completely attributed to a cAMP
      dependent pathway. The wide range of inflammatory mechanisms controlled by PDE4
      designated these enzymes as a good target for anti-inflammatory compounds. PDE4
      inhibitors have been demonstrated to be very potent in the treatment of chronic
      inflammatory diseases like asthma or chronic obstructive pulmonary disease (COPD)
      but their therapeutic window has yet to be improved.

PMID- 12185966
TI  - [Plasmatic dosage of antiretroviral drugs by high performance liquid
      chromathography ].
AB  - A high-performance liquid chromatographic method has been developed for the
      determination of eight antiretroviral drugs (amprenavir, indinavir, lopinavir,
      nelfinavir, ritonavir, saquinavir, efavirenz and nevirapine) in a single run.
      After a liquid-liquid extraction with diethylether, the antiretroviral drugs are
      separated on a Stability RP18 column eluted with a gradient of acetonitrile and
      phosphate buffer (50 mM pH 5.65). A sequential ultraviolet detection allowed for
      simultaneous quantitation of antiretroviral drugs (240, 215, 260 nm). Calibration
      curves were linear in the range 100-10,000 ng/ml. The limit of quantitation was
      50 ng/ml for all drugs except for nevirapine (100 ng/ml). The accuracies ranged
      from 88.2% to 110.9% and both inter- and intra-day coefficients of variation were
      lower than 11%. The extraction recoveries were higher than 62%. This method is
      simple and shows good specificity with respect to commonly coprescribed drugs.

PMID- 12185967
TI  - [Methods of evaluation of risks tied to drug exposure during pregnancy.
      Advantages and limits of epidemiology, interpretation of results].
AB  - Various epidemiologic designs permit an evaluation of drug teratogenicity, but
      none is sufficient to establish the risk. Only concordance of results of several
      studies lead a substance to be considered teratogenic. The usual designs of
      analytical epidemiology can be used: prospective studies of total populations,
      case-control, cohort. Case series may be useful when no good epidemiologic study
      is available. Most of those published were collected by teratogen information
      services (TISs). These series of exposures are not representative samples of the
      general population, and when interpreting the pregnancy outcomes, it is difficult
      to define an unexposed group for comparison. In practice, if 50 pregnancies are
      reported with early exposure to a given drug and without unwanted effects, one
      can exclude a strong teratogenic effect, and reassure a woman inadvertently
      exposed. TISs have published several of such exposure series, and they are often
      used. On the contrary, if the question arises whether or not to prescribe a drug
      to a woman in early pregnancy, a much larger sample of pregnancy with known
      outcomes is needed to answer "yes": this is a situation of population risk
      assessment, because one would give the same answer to all similar questions,
      which may be many. Birth-defect monitoring systems are in a better position to do
      this and several examples can be given (valproate and spina bifida,
      corticosteroids and orofacial clefts).

PMID- 12185968
TI  - [Long-term psychiatric and behavioural consequences of prenatal exposure to
      psychoactive drugs].
AB  - A growing body of evidence supports the hypothesis that exposure to prenatal
      environmental risk factors increases the vulnerability for a broad range of
      psychiatric disorders. Although the association between exposure to obstetric
      complications and increased vulnerability for psychiatric disorders is well
      documented, few studies have explored the putative deleterious impact of
      psychoactive substances and xenoestrogens on subsequent liability for
      psychological disturbances. Cohort studies suggest that prenatal exposure to
      nicotine is a risk factor for conduct disorders, and some case-control studies
      have reported an association between prenatal nicotine exposure and attention
      deficit hyperactivity disorder. Studies on the long-term behavioural consequences
      of prenatal exposure to other licit and illicit psychoactive substances are
      hampered by methodological flaws limiting the interpretation of the findings.
      Regarding prenatal exposure to hormones, sparse findings suggest that exposure to
      xenoestrogens such as diethylstilbestrol may be a risk factor for psychiatric
      disorders, mediated by a deleterious impact of these substances on the foetal
      neurodevelopment. However, this hypothesis is largely speculative due to the low
      number of studies and their methodological limitations. Further studies are
      required to explore the long-term cognitive and behavioural consequences of
      prenatal exposure to psychoactive drugs and xenoestrogens.

PMID- 12185969
TI  - [ Legal aspects of advice provided by an institutional pharmacovigilance
      specialist to health-care professionals. Consequences in the field of teratology
      ].
AB  - An institutional pharmacovigilance specialist gives advice only when consulted by
      a prescribing physician about a pregnant woman. The situation may involve a
      pregnant woman for whom a prescription may be considered or a pregnant woman for
      whom a prescription has been given. The aim is to evaluate the risk for the
      fetus, both before and after the fact. In view of recent decisions by the Cour de
      Cassation (*) which imposed penalties for preventing a woman exposed to a
      teratogenic risk from resorting to an abortion by providing her with inapropriate
      information, we are suggesting here the hypothesis that an institutional
      pharmacovigilance specialist acting as a consultant could be implicated. However,
      this hypothesis is purely academic. If action were taken to render a
      pharmacovigilance specialist liable, it is in fact the State that would have to
      answer.

PMID- 12185970
TI  - [Utilization of methylphenidate(Ritalin) in France].
AB  - Methylphenidate (Ritalin) is the only psychostimulant approved in France and
      indicated in attention deficit hyperactivity disorder in children over 6 years.
      It is under restricted prescription and distribution conditions. As such, it
      requires a hospital initiated prescription from either a neurology, psychiatry or
      pediatric specialist and it is covered by the "narcotics" schedule. The French
      Pharmacovigilance database spontaneous adverse drug reactions reporting, since it
      was approved in 1995, were analyzed. 21 adverse drug reactions were reported. In
      16 cases, methylphenidate was suspected. They were generally non-serious, mild
      side effects and in most cases promptly resolved. These results do not suggest
      methylphenidate misuse in France or an overuse in between 1300 and 4000 treated
      children, to date. Until more information is available concerning the long-term
      effects of methylphenidate, and in order to limit misuse, inappropriate or
      overuse, the current prescription and dispensing regulation should be maintained
      in France, and could well be developed in other countries.

PMID- 12185971
TI  - [Severe oedema after valproate and valpromide].

PMID- 12185972
TI  - [Post-marketing surveillance information transmitted via electronic mail in a
      University Hospital].

PMID- 12185973
TI  - [OPPIDUM, a tool for assessing the local misuse of psychotropic drugs?].

PMID- 12185974
TI  - [Correspondents in post- marketing surveillance, drug dependence surveillance,
      and toxicovigilance: definition and roles].

PMID- 12185976
TI  - [Use and misuse of triptans: a case report].

PMID- 12185975
TI  - [Is nitroxoline an allergen?].

PMID- 12185977
TI  - [Drug error, drug delivery and information systems: a case report].

PMID- 12185978
TI  - Benzodiazepines and the risk of falling.

PMID- 12185979
TI  - A transcription toolkit: theoretical and clinical considerations.
AB  - This paper discusses theoretical and clinical aspects of transcription practices
      in clinical linguistics and phonetics, and speech-language pathology. We consider
      the purpose of transcribing and transcripts, and distinguish between the
      transcript as a product and transcribing as a complex, cyclical process that
      forms an integral part of data analysis. Operational relationships between
      transcriber, data and data source, and the reader are addressed. We suggest a
      multi-layered toolkit approach to transcribing, based on six guiding principles.

PMID- 12185980
TI  - The base layer and the gaze/gesture layer of transcription.
AB  - This article focuses on two initial layers of transcription important to the
      transcription tool kit. Employing several examples from previous work, the basic
      orthographic layer of transcription and the layer involving interactional gaze
      and symbolic gesture are discussed and described. These two layers of
      transcription are often essential to the transcription and understanding of
      communication as social action.

PMID- 12185981
TI  - Transcribing disordered speech: the segmental and prosodic layers.
AB  - In this article we explore the speech layers of a transcription toolkit. We begin
      by discussing issues of transcription theory and practice, including the
      difference between broad and narrow phonetic transcription and the importance of
      narrow transcription with disordered speech, and the measurement of transcriber
      reliability. We also look at extending symbol sets and using instrumental
      approaches to deal with atypical speech production. Both segmental and prosodic
      transcription are dealt with in turn and illustrated with sample transcriptions.
      We note that, while several phenomena can be subsumed under the prosodic layer,
      less agreement exists on how to transcribe these than with segmental examples,
      and that little agreement yet exists on how to notate prosodic disorders. We
      conclude with illustrations from various adult and child cases.

PMID- 12185982
TI  - Transcribing discourse: interactions with Alzheimer's disease.
AB  - This paper illustrates the use of a 'discourse line' in transcribing spoken
      interaction between a person with Alzheimer's disease, and a visitor. Discourse
      is here interpreted as a metacategory, or an analytic level of interaction. We
      view transcribing as an integral part of 'doing discourse', and use two sub
      layers of the discourse line, dedicated to speech acts and conversation analysis,
      respectively. The prosody and voice layer is used to show the analysis of a
      speaker's use of a specific voice quality in discourse terms.

PMID- 12185983
TI  - The clinical analysis layer of transcription.
AB  - The clinical analysis layer of transcription is part of a 'toolkit' approach for
      detailed analysis of communication samples. This article provides a rationale for
      using the clinical analysis strategy and is supported by several examples of how
      a clinical analysis layer can add to the understanding of communication errors or
      other clinical areas of interest. The examples used in this paper are drawn from
      the areas of stuttering and aural rehabilitation and demonstrate the utility of
      this clinical analysis layer of transcription.

PMID- 12185984
TI  - Learning and teaching phonetic transcription for clinical purposes.
AB  - This paper explores the theoretical issues surrounding clinical phonetic
      transcription which are pertinent to the education of speech and language therapy
      students. It draws on theoretical literature and practical experience, to
      consider issues of rationale, timing, structure, and content of courses in
      phonetic transcription for clinical purposes, and explores the problems and
      pitfalls inherent in the process. It is not a tutorial in clinical practical
      phonetics, but an examination of the issues which teachers of the subject need to
      consider in delivering such courses.

PMID- 12185985
TI  - Lost sleep....

PMID- 12185986
TI  - Acupuncture: a physician's primer, Part I.
AB  - Acupuncture is one of the alternative therapies that is quickly gaining
      popularity and acceptance among both patients and doctors. The NIH has supported
      its use for many conditions, alone or as adjunctive therapy to conventional
      methods. Research has now demonstrated several physiological mechanisms to
      explain acupuncture's benefits. However, there are many different schools of
      acupuncture, and methodology and techniques vary widely, all contributing to the
      success or failure of acupuncture treatment. With proper use, acupuncture can be
      an effective treatment for a variety of medical conditions, but used incorrectly,
      it can be a waste of time and resources.

PMID- 12185987
TI  - The place of the nasogastric tube.
AB  - Physicians frequently take care of patients in hospital and emergency room
      settings where they have to utilize a variety of invasive diagnostic and
      therapeutic procedures in patient care. It is important that we be fully aware of
      the potential for complications and limitations of these techniques. The use of
      the nasogastric tube in patient care is not without adverse effects, and recent
      literature has called its routine use into question for a variety of situations.
      This paper is an attempt to illustrate some of these concerns, and suggests that
      physicians exercise greater restraint and judgment when considering its use.

PMID- 12185988
TI  - Childhood obesity: why is this happening to our children?
AB  - Obesity among children is epidemic in the U.S. Although a serious problem because
      of the rising incidence of Type II diabetes as well as heart disease, it is
      preventable. Unfortunately, it is difficult to prevent because of the problem of
      getting people to change dietary habits and increase their physical activity.
      However, it is a serious enough health issue to require the attention and actions
      of physicians.

PMID- 12185989
TI  - Abstracts of the 6th Congress of the European Society of Contact Dermatitis. 14
      16 June 2002, Rome, Italy.

PMID- 12185990
TI  - Targeting peroxisome proliferator-activated receptors (PPARs) in kidney and
      urologic disease.
AB  - Peroxisome proliferator-activated receptors (PPARs) are members of the nuclear
      hormone receptor superfamily of ligand-activated transcription factors. Three
      PPAR isoforms, designated PPAR-alpha, beta/delta and -gamma, have been identified
      and were initially investigated in the tissues along urinary tract because of
      their known role in regulating lipid-activated gene transcription, lipid
      metabolism, inflammation and cell proliferation and differentiation. Gene
      distribution studies suggested that 3 PPAR isoforms are differentially expressed
      in the kidney. PPAR-alpha is predominantly expressed in renal proximal tubules
      and medullary thick ascending limbs. PPAR-gamma is mainly localized in renal
      medullary collecting duct with lower expression in renal glomeruli and renal
      microvasculature. Unlike PPAR-alpha and -gamma, PPAR-beta/delta is ubiquitously
      expressed in every segment along the nephron. In ureter and urinary bladder, all
      PPAR isoforms are mainly localized in urothelium of ureter and bladder. The
      emerging data have suggested physiological and pathophysiological roles of PPARs
      in tissues along urinary tract. PPAR-alpha plays a major role in triggering fatty
      acid utilization and the adaptive response to dietary lipids in the kidney. PPAR
      beta/delta contributes to cell survival of renal interstitial cell in medullary
      hyperosmality. PPAR-gamma is involved in regulating renal hemodynamic and water
      and sodium transport. Furthermore, it also participates in the pathogenesis of
      glomerulopathy, antidiabetic thiazolidinedione-related water and sodium retention
      and renal, bladder and prostate carcinomas. PPARs may serve as potential
      therapeutic targets for certain diseases along urinary tract including
      glomerulosclerosis, diabetic nephropathy and kidney, prostate and bladder tumors.

PMID- 12185991
TI  - Re: Multiple corticosteroid allergies. Australas. J. Dermatol. 2001; 42: 62-3.

PMID- 12185992
TI  - Tinea incognita vs. tinea incognito.

PMID- 12185994
TI  - Surgical treatment of inflammatory disease of the thyroid.

PMID- 12185993
TI  - Fine-needle aspiration biopsy of the thyroid: comparison between thyroid
      palpation and ultrasonography.
AB  - OBJECTIVE: To describe our experience with fine-needle aspiration biopsy (FNAB)
      of the thyroid and compare our results with direct palpation versus ultrasound
      scanning (USS) in an area of endemic goiter in Italy. METHODS: We considered all
      patients submitted to ultrasound-guided FNAB of thyroid nodules during a 10-month
      period at our outpatient clinic and analyzed the following: (1) clinical data
      (number of nodules and identification of the nodule for FNAB); (2) USS data
      (number of nodules and identification of the nodule for FNAB on the basis of
      hypoechoic pattern + blurred perinodal halo + microcalcifications or intranodal
      color Doppler signal indicative of blood flow); (3) cytologic specimens,
      categorized as suspicious, malignant, negative, or nondiagnostic; and (4)
      histologic final report of the cytologically positive nodules. RESULTS: The study
      group consisted of 348 female and 72 male patients who underwent FNAB of the
      thyroid at our institution. Among the 140 patients with no palpable thyroid
      nodules, USS showed that 106 had a single nodule and 34 had multinodular goiters.
      Among the 182 patients with a single palpable thyroid nodule, USS revealed that
      138 had a single nodule, 42 had a multinodular goiter, and 2 had lobe enlargement
      without detectable nodules. All 98 patients with multinodular palpable goiter had
      a similar pattern on USS. Of the 420 cytologic specimens, 46(11.0%) were positive
      for thyroid cancer, 313 (74.5%)were negative, and 61 (14.5%) were nondiagnostic.
      Histologic malignant growth was confirmed in 27 cytologically positive nodules.
      Of these histologically malignant nodules, 12 (45%) were nonpalpable, 9 (33%)
      were single palpable nodules, and 6 (22%) were from a nodule with a suspicious
      ultrasound pattern within a multinodular goiter. CONCLUSION: Manually guided FNAB
      is not feasible in nonpalpable nodules and not accurate in a multinodular goiter.
      Both situations are clinical challenges, and USS should be performed for accurate
      FNAB under these circumstances. Because 52% of histologically malignant nodules
      in our study were found only with the aid of ultrasound-guided FNAB, this
      procedure should be used where multinodular goiter is endemic. Our overall rate
      of nondiagnostic specimens was comparable to that reported in the literature.

PMID- 12185995
TI  - Visual vignette. Idiopathic diabetes insipidus.

PMID- 12185997
TI  - NCI-EORTC 2nd International Meeting on Cancer Diagnosis: From Discovery to
      Clinical Practice. June 26-29, 2002. Washington, DC, USA. Abstracts.

PMID- 12185998
TI  - Abstracts of the Vascular Society of Southern Africa 2001 Congress. Bakubung, 8
      12 August 2001.

PMID- 12185996
TI  - Fen-Phen-noumenon: A mass tort litigation and settlement about to come and go.

PMID- 12185999
TI  - [Respiratory Medicine in 2001].

PMID- 12186000
TI  - Abstracts of the 12th Meeting of the European Neurological Society. 22-26 June
      2002, Berlin, Germany.

PMID- 12186002
TI  - Gene therapy coming of age in Latin America.
AB  - "Gene Therapy in Latin America: From the Bench to the Clinic," a meeting
      sponsored by the Wellcome Trust and the United Nations University through the
      Biotechnology Program for Latin America and the Caribbean, took place in Buenos
      Aires, Argentina from May 20 to 22. This symposium, which was hosted by Osvaldo
      Podhajcer and Fernando Pitossi,had more than 150 basic scientists and physician
      scientists from academia, government and industry in Latin America, similar to
      the first meeting of the Asociacion Iberoamericana de Terapia Genica
      (Iberoamerican Society of Gene Therapy, AITG) held in Guadalajara, Mexico, two
      years ago. Participants represented Argentina, Mexico, Brazil, Chile, Uruguay,
      Costa Rica, Colombia, Venezuela, and Guatemala, with guests from the United
      States and Europe. All came together to discuss the latest developments in this
      field in the region. A primary objective of this gathering was to bring together
      Latin American scientists involved in gene therapy to strengthen continental
      collaborations and to further disseminate the scientific expertise available in
      Latin America. The symposium was followed by a 10-day practical course for 25
      students from all over Latin America.

PMID- 12186001
TI  - The value and practice of attenuation correction for myocardial perfusion SPECT
      imaging.

PMID- 12186003
TI  - Abstracts of the 8th International Conference on Malignant Lymphoma. 12-15 June
      2002. Lugano, Switzerland.

PMID- 12186005
TI  - Abstracts of the 6th European Headache Federation Congress. 26-30 June 2002.
      Istanbul, Turkey.

PMID- 12186004
TI  - Abstracts of the 37th German Congress of Sports Medicine and Prevention.
      September 26-30, 2001. Rotenburg a.d. Fulda, Germany.

PMID- 12186007
TI  - Abstracts of the 8th Annual Meeting of the German Society of Radiation Oncology.
      Berlin, Germany, 29 June-2 July 2002.

PMID- 12186006
TI  - European Society for Therapeutic Radiology and Oncology 6th biennial meeting of
      physics in clinical radiotherapy and 6th meeting on radiation technology for
      clinical radiotherapy. Workshop on verification of IMRT. Sevilla, 15-20 September
      2001. Abstracts.

PMID- 12186008
TI  - Abstracts of the 10th Congress of the European Shock Society. Oslo, Norway.
      September 5-7, 2002.

PMID- 12186009
TI  - [2nd National Congress of Research and Health, National Institute of Health,
      Colombia. Abstracts].

PMID- 12186010
TI  - Proceedings of the VA/NIH Prosthetics Roundtable. June 25, 2001.

PMID- 12186011
TI  - Abstracts of the 2nd Conference on Epidemiological Longitudinal Studies in
      Europe. 12-14 June 2002. Oulu, Finland.

PMID- 12186012
TI  - Abstracts of the American Association of Oral and Maxillofacial Surgeons 84th
      Annual Meeting. October 2-5, 2002. Chicago, Illinois, USA.

PMID- 12186013
TI  - I am now too scared to have surgery.

PMID- 12186015
TI  - Abstracts of the 73rd Congress of the European Atherosclerosis Society. Salzburg,
      7-10 July 2002.

PMID- 12186014
TI  - Intrasite Gel in the care of patients.

PMID- 12186016
TI  - Three-dimensional propagation effects near the mid-Atlantic Bight shelf break.

PMID- 12186017
TI  - Transition from transient response to steady state for a layered medium.
AB  - The transition from transient response to steady-state for a layered medium
      subjected to antiplane loadings is studied. The steady-state formula for a
      layered medium is derived and the solutions for a layered half-space are then
      expressed explicitly in the form of wave number integrals. The transient response
      solutions for a layered half-space are obtained by the convolution of time
      harmonic loading function with transient response formula derived analytically
      from an effective matrix method. Two layered half-spaces with different ratios of
      wave velocities in the layer and half-space are considered and investigated by
      means of extensive numerical results to show their quite different transition
      behavior. The numerical results indicate that transient responses will approach
      steady state after certain characteristic times when the transient effects die
      away. The transition phenomena and characteristic times are investigated in
      detail through the responses from near field to far field as well as from low
      frequency to high frequency.

PMID- 12186018
TI  - Linear time domain model of the acoustic potential field.
AB  - A new time domain formulation of the acoustic wave is developed to avoid
      approximating assumptions of the linearized scalar wave equation that limit its
      validity to low Mach particle velocity modeling or to a smooth potential field in
      a stationary medium. The proposed model offers precision of the moving frame
      while retaining the form of the widely used linearized scalar wave equation
      although with respect to modified coordinates. It is applicable to field
      calculations involving transient waves with unlimited particle velocity,
      propagating in inhomogenous fluids or in those with time varying density. The
      model is based on the exact flux continuity equation and the equation of motion,
      both using the moving reference frame. The resulting closed-form free space
      scalar wave equation employing total derivatives is converted back to the partial
      differential form by using modified independent variables. The modified variables
      are related to the common coordinates of space and time following integral
      expressions involving transient particle velocity representing wave radiated by
      each point of a stationary source. Consequently, transient field produced by
      complex surface velocity sources can be calculated following existing surface
      integrals of the radiation theory although using modified coordinates. The use of
      the proposed model is presented in a numerical simulation of a transient velocity
      source vibrating at selected magnitudes, leading to the determination of the
      propagating pressure and velocity wave at any point.

PMID- 12186019
TI  - Free molecular sound propagation.
AB  - The sound propagation through a gas in the free-molecular regime is studied on
      the basis of the linearized collisionless Boltzmann equation. The two principal
      quantities that characterize the sound propagation, namely the phase and
      amplitude of the perturbation, are determined by taking into account the
      influence of the receptor. It is shown that at a small distance between the
      source and the receptor the presence of the last changes qualitatively the sound
      characteristics. Two phase velocities are introduced: a differential and an
      integral, which are different in the free molecular regime.

PMID- 12186020
TI  - Scattering from a ribbed finite cylindrical shell with internal axisymmetric
      oscillators.
AB  - A theoretical formalism is elaborated to determine the acoustic field scattered
      from a finite cylindrical shell reinforced by a set of ribs with internal
      axisymmetric oscillators, the locations and properties of which can vary
      arbitrarily along the cylinder axis. Analytical expressions are derived for the
      scattered pressure and approximate expressions are proposed to calculate the
      backscattered field. Some applications have been carried out to investigate the
      problem of backscattering from a periodically ribbed finite cylindrical shell in
      the presence of rib aperiodicity or axisymmetric internal oscillators. The
      modifications of the main features associated with scattering from helical and
      Bloch-Floquet waves are examined and numerical results are presented with respect
      to the mean rib spacing and to the total mass of the internal structures.

PMID- 12186021
TI  - Analysis of the time-reversal operator for scatterers of finite size.
AB  - Recently, it was shown that the time-reversal operator for a single, small
      spherical scatterer could have up to four distinguishable eigenstates [Chambers
      and Gautesen, J. Acoust. Soc. Am. 109, 2616-2624 (2001)]. In this paper, that
      analysis is generalized for scatterers of arbitrary shape and larger size. It is
      shown that the time-reversal operator may have an indefinitely large number of
      distinguishable eigenstates, with the exact number depending on the nature of the
      scatterer and the geometry of the time-reversal mirror. In addition, the case of
      a multiple number of well-separated scatterers is investigated, with the result
      that the total spectrum is the direct combination of the eigenstates associated
      with each scatterer. As an example, the singular value spectrum of the time
      reversal operator for a linear array is calculated explicitly for bubbles and
      hard rubber spheres of finite size. Both resonance peaks and apparent crossing
      points can be observed in the spectrum as the size of the scatterer increases.

PMID- 12186022
TI  - Planar near-field acoustical holography in a moving medium.
AB  - Near-field acoustical holography (NAH) is a well-established method to study
      acoustic radiation near a stationary sound source in a homogeneous, stationary
      medium. However, the current theory of NAH is not applicable to moving sound
      sources, such as automobiles and trains. In this paper, the inclusion of a moving
      medium (i.e., moving source and receiver) is introduced in the wave equation and
      a new set of equations for plannar NAH is developed. Equations are developed for
      the acoustic pressure, particle velocity, and intensity when mean flow is either
      parallel or perpendicular to the hologram plane. If the source and the
      measurement plane are moving at the same speed, the frequency Doppler effect is
      absent, but a wave number Doppler effect exists. This leads to errors when
      reconstructing the acoustic field both towards and away from the source using
      static NAH. To investigate these errors, a point source is studied analytically
      using planar NAH with flow in one direction. The effect of the medium moving
      parallel to the hologram plane is noted by a shift of the radiation circle in
      wave number space (k-space). A k-space Green's function and a k-space filter are
      developed that include the effects of the moving medium.

PMID- 12186023
TI  - Resonance analysis of a 2D alluvial valley subjected to seismic waves.
AB  - The T-matrix formalism and an ultrasonic experiment are developed to study the
      scattering of in-plane waves for an alluvial valley embedded in a two-dimensional
      half-space. The solution of the in-plane scattering problem can be determined by
      the T-matrix method, where the basis functions are defined by the singular
      solutions of Lamb's problems with surface loading in both horizontal and vertical
      directions. In the experiment, a thin steel plate with a semicircular aluminum
      plate attached on the edge is used to simulate the two-dimensional alluvial
      valley in the state of plane stress. Based on the spectra of displacement signals
      measured at the free edge of the scatterer, the resonance frequencies where the
      peaks appear can be identified. It can be shown that the nondimensional resonance
      frequency is one of the characteristic properties of the scattering system.
      Furthermore, it is noted that the nondimensional resonance frequencies measured
      experimentally are in good agreement with those calculated theoretically.

PMID- 12186024
TI  - Acoustic streaming related to minor loss phenomenon in differentially heated
      elements of thermoacoustic devices.
AB  - It is demonstrated that the differentially heated stack, the heart of all
      thermoacoustic devices, provides a source of streaming additional to those
      associated with Reynolds stresses in quasi-unidirectional gas flow. This source
      of streaming is related to temperature-induced asymmetry in the generation of
      vortices and turbulence near the stack ends. The asymmetry of the hydrodynamic
      effects in an otherwise geometrically symmetric stack is due to the temperature
      difference between stack ends. The proposed mechanism of streaming excitation in
      annular thermoacoustic devices operates even in the absence of thermo-viscous
      interaction of sound waves with resonator walls.

PMID- 12186025
TI  - A linearized Eulerian sound propagation model for studies of complex
      meteorological effects.
AB  - Outdoor sound propagation is significantly affected by the topography (including
      ground characteristics) and the state of the atmosphere. The atmosphere on its
      part is also influenced by the topography. A sound propagation model and a flow
      model based on a numerical integration of the linearized Euler equations have
      been developed to take these interactions into account. The output of the flow
      model enables the calculation of the sound propagation in a three-dimensionally
      inhomogeneous atmosphere. Rigid, partly reflective, or fully absorptive ground
      can be considered. The linearized Eulerian (LE) sound propagation model has been
      validated by means of four different scenarios. Calculations of sound fields
      above rigid and grass-covered ground including a homogeneous atmosphere deviate
      from analytic solutions by < or = 1 dB in most parts of the computed domain.
      Calculations of sound propagation including wind and temperature gradients above
      rigid ground agree well with measured scale model data. Calculations of sound
      propagation over a screen including ground of finite impedance show little
      deviations to measured scale model data which are probably caused by an
      insufficient representation of the complex ground impedance. Further calculations
      included the effect of wind on shading by a screen. The results agree well with
      the measured scale model data.

PMID- 12186026
TI  - Breaking wind waves as a source of ambient noise.
AB  - A theoretical model for the prediction of ambient noise level due to collective
      oscillations of air bubbles under breaking wind waves is presented. The model
      uses a budget of the energy flux from the breaking waves to quantify acoustic
      power radiation by a bubble cloud. A shift of the noise spectra to lower
      frequency due to collective bubble oscillation is assumed. The model derives good
      estimates of the magnitude, slope, and frequency range of the noise spectra using
      the wind speed or height of breaking waves.

PMID- 12186027
TI  - Wavefronts and waveforms in deep-water sound propagation.
AB  - A new method of calculating waveforms in underwater sound propagation is
      presented. The method is based on a Hankel transform-generalized Wentzel-Kramers
      Brillouin (WKB) solution of the wave equation. The resulting integral leads to a
      new form of ray theory which is valid at relatively low frequencies and allows
      evaluation of the acoustic field on both the illuminated and shadow sides of
      caustics and at cusps where two caustics meet to form a focus. The integral is
      evaluated by stationary phase methods for the appropriate number of stationary
      points. Rays of nearby launch angle which have a travel time difference less than
      a quarter period must be considered together. The description of all other ray
      arrivals corresponds to simple ray theory. The phase, amplitude, and travel time
      of broadband acoustic pulses are obtainable directly from a simple graph of ray
      travel time as a function of depth at a given range. The method can handle range
      dependence but is illustrated here in long-distance propagation in deep water
      where the ray paths do not pass close to surface or bottom. The method is fast
      and gives close agreement with normal-mode calculations. The field on the shadow
      side of a caustic is properly given in terms of rays with complex launch angles,
      but good approximations can be obtained without the need to find complex rays.

PMID- 12186028
TI  - A two-way parabolic equation that accounts for multiple scattering.
AB  - A two-way parabolic equation that accounts for multiple scattering is derived and
      tested. A range-dependent medium is divided into a sequence of range-independent
      regions. The field is decomposed into outgoing and incoming fields in each
      region. The conditions between vertical interfaces are implemented using rational
      approximations for the square root of an operator. Rational approximations are
      also used to relate fields between neighboring interfaces. An iteration scheme is
      used to solve for the outgoing and incoming fields at the vertical interfaces.
      The approach is useful for solving problems involving scattering from waveguide
      features and compact objects.

PMID- 12186029
TI  - Surf-generated noise signatures: a comparison of plunging and spilling breakers.
AB  - Range-time-frequency distributions of surf-generated noise were measured within
      the surf zone during the SandyDuck'97 experiment at Duck, NC. A 24-phone, 138-m,
      bottom-mounted, linear array located along a line perpendicular to the shore at a
      depth of 1 to 3 m recorded the surf-generated noise. Concurrent video
      measurements of the location, size, and time-evolution of the individual breaking
      waves directly above the array were made from a nearby 43-m tower. Source level
      spectra are obtained by using a modified fast field program to account for water
      column and geoacoustic propagation from the distributed source region to an
      individual hydrophone. The length, location, and orientation of the leading edge
      of breakers are tracked in time from rectified video images. It is observed that
      the source levels from spilling breakers are lower (approximately 5-10 dB) than
      those produced by plunging breakers that occurred during the same time period.
      Plunging breakers generated time-frequency signatures with a sharp onset while
      spilling breakers' signatures had a gradual low-frequency precursor. Range-time
      signatures of plunging breakers indicate a burst of acoustic energy while
      spilling breakers' signatures depict sound being generated over a longer time
      period with the source region moving with the breaking surface wave.

PMID- 12186030
TI  - Multibeam volume acoustic backscatter imagery and reverberation measurements in
      the northeastern Gulf of Mexico.
AB  - Multibeam volume acoustic backscatter imagery and reverberation measurements are
      derived from data collected in 200-m-deep waters in the northeastern Gulf of
      Mexico, with the Toroidal Volume Search Sonar (TVSS), a 68-kHz cylindrical sonar
      operated by the U.S. Navy's Coastal System Station. The TVSS's 360-degree
      vertical imaging plane allows simultaneous identification of multiple volume
      scattering sources and their discrimination from backscatter at the sea surface
      or the seafloor. This imaging capability is used to construct a three-dimensional
      representation of a pelagic fish school near the bottom. Scattering layers imaged
      in the mixed layer and upper thermocline are attributed to assemblages of
      epipelagic zooplankton. The fine scale patchiness of these scatterers is assessed
      with the two-dimensional variance spectra of vertical volume scattering strength
      images in the upper and middle water column. Mean volume reverberation levels
      exhibit a vertical directionality which is attributed to the volume scattering
      layers. Boundary echo sidelobe interference and reverberation is shown to be the
      major limitation in obtaining bioacoustic data with the TVSS. Because net tow and
      trawl samples were not collected with the acoustic data, the analysis presented
      is based upon comparison to previous biologic surveys in the northeastern Gulf of
      Mexico and reference to the bioacoustic literature.

PMID- 12186031
TI  - Thermodynamic efficiency of thermoacoustic mixture separation.
AB  - The acoustic power loss in the thermoacoustic mixture-separation process is
      derived, including the contributions due to a nonzero gradient in concentration.
      The significance of the gradient-dependent term is discussed. The limiting
      thermodynamic efficiency of the separation is calculated. Under reasonable
      circumstances, the efficiency approaches 10(-2) nHnL(delta m/m(avg))2, where nH
      and nL are the mole fractions of the two components of the mixture, and delta
      m/m(avg) is the fractional difference between the molar masses of the two
      components. This efficiency is of the same order of magnitude as that of some
      other, more conventional separation methods.

PMID- 12186032
TI  - Study on the prestressed sandwich piezoelectric ceramic ultrasonic transducer of
      torsional-flexural composite vibrational mode.
AB  - Based on the classical torsional and flexural vibrational theory of a slender
      rod, the prestressed sandwich torsional-flexural composite mode piezoelectric
      ceramic ultrasonic transducer is studied. This type of transducer consists of the
      slender metal rods and the longitudinally and tangentially polarized
      piezoelectric ceramic rings. The resonance frequency equations for the torsional
      and flexural vibrations in the transducers are derived. The simultaneous
      resonance of the torsional and flexural vibrations in the transducer is acquired
      by correcting the length of the metal slender rods resulting from the
      piezoelectric ceramic elements. The experimental results show that the measured
      resonance frequencies of the transducers are in good agreement with the computed
      ones, and the measured resonance frequencies of the torsional and the flexural
      vibrations in the composite transducers are also in good agreement with each
      other.

PMID- 12186033
TI  - Applications of the direct Trefftz boundary element method to the free-vibration
      problem of a membrane.
AB  - In this paper, the direct Trefftz method is applied to solve the free-vibration
      problem of a membrane. In the direct Trefftz method, there exists no spurious
      eigenvalue. However, an ill-posed nature of numerical instability encountered in
      the direct Trefftz method requires some treatments. The Tikhonov's regularization
      method and generalized singular-value decomposition method are used to deal with
      such an ill-posed problem. Numerical results show the validity of the current
      approach.

PMID- 12186034
TI  - Leaky helical flexural wave backscattering contributions from tilted cylindrical
      shells in water: observations and modeling.
AB  - For tilt angles smaller than the meridional ray coupling condition previously
      investigated [S. F. Morse et al., J. Acoust. Soc. Am. 103, 785-794 (1998)],
      flexural helical waves on cylindrical shells can significantly enhance the
      backscattering. These contributions are compared and modeled here for an empty
      cylinder. Experiments using tone bursts were performed on a tilted stainless
      steel shell to investigate the contributions caused by flexural leaky Lamb waves
      above the coincidence frequency of the shell. In some of the measurements the
      tone bursts were of sufficient duration to superpose helical wave contributions
      of successive circumnavigations, along with the meridional contribution near the
      critical tilt, to arrive at a quasi-steady-state backscattering amplitude for the
      cylinder. These measurements are compared with an approximate numerical partial
      wave series solution and a ray theory as a function of the tilt angle. The data
      for ka = 20 follow the basic shape of the ray theory and the relevant features of
      the partial-wave model. They illustrate the importance of the interference of
      successive helical wave contributions. Measurements (also as a function of the
      tilt angle) using tone bursts that were sufficiently short to separate the
      earliest helical wave contribution from later contributions also support the ray
      theory.

PMID- 12186035
TI  - The propagation of sound in narrow street canyons.
AB  - This paper addresses an important problem of predicting sound propagation in
      narrow street canyons with width less than 10 m, which are commonly found in a
      built-up urban district. Major noise sources are, for example, air conditioners
      installed on building facades and powered mechanical equipment for repair and
      construction work. Interference effects due to multiple reflections from building
      facades and ground surfaces are important contributions in these complex
      environments. Although the studies of sound transmission in urban areas can be
      traced back to as early as the 1960s, the resulting mathematical and numerical
      models are still unable to predict sound fields accurately in city streets. This
      is understandable because sound propagation in city streets involves many
      intriguing phenomena such as reflections and scattering at the building facades,
      diffusion effects due to recessions and protrusions of building surfaces,
      geometric spreading, and atmospheric absorption. This paper describes the
      development of a numerical model for the prediction of sound fields in city
      streets. To simplify the problem, a typical city street is represented by two
      parallel reflecting walls and a flat impedance ground. The numerical model is
      based on a simple ray theory that takes account of multiple reflections from the
      building facades. The sound fields due to the point source and its images are
      summed coherently such that mutual interference effects between contributing rays
      can be included in the analysis. Indoor experiments are conducted in an anechoic
      chamber. Experimental data are compared with theoretical predictions to establish
      the validity and usefulness of this simple model. Outdoor experimental
      measurements have also been conducted to further validate the model.

PMID- 12186036
TI  - A multiple regression model for urban traffic noise in Hong Kong.
AB  - This article describes the roadside traffic noise surveys conducted in heavily
      built-up urban areas in Hong Kong. Noise measurements were carried out along 18
      major roads in 1999. The measurement data included L10, L50, L90, Leq, Lmax, the
      number of light vehicles, the number of heavy vehicles, the total traffic flow,
      and the average speed of vehicles. Statistical analysis using the analysis of
      variance (ANOVA) and Tukey test (p<0.05) reveals that the total traffic flow and
      the number of heavy vehicles are the most significant factors of urban traffic
      noise. Multiple regression was used to derive a set of empirical formulas for
      predicting L10 noise level due to road traffic. The accuracy of these empirical
      formulas is quantified and compared to that of another widely used prediction
      model in Hong Kong--the Calculation of Road Traffic Noise. The applicability of
      the selected multiple regression model is validated by the noise measurements
      performed in the winter of 2000.

PMID- 12186037
TI  - Distribution of risk factors for hearing loss: implications for evaluating risk
      of occupational noise-induced hearing loss.
AB  - This paper presents an analysis of hearing threshold levels among 2066 white male
      workers employed in various U.S. industries studied in the 1968-72 NIOSH
      Occupational Noise and Hearing Survey (ONHS). The distribution of hearing
      threshold levels (HTL) is examined in relation to various risk factors (age,
      prior occupational noise, medical conditions) for hearing loss among a population
      of noise exposed and control (low noise-exposed) industrial workers. Previous
      analyses of a subset of these data from the ONHS focused on 1172 highly
      "screened" workers. An additional 894 male workers (609 noise-exposed and 285
      controls), who were excluded for various reasons (i.e., nonoccupational noise
      exposure, otologic or medical conditions affecting hearing, prior occupational
      noise exposure) have been added to examine hearing loss in an unscreened
      population. Data are analyzed by age, duration of exposure, and sound level (8-h
      TWA) by individual test frequency. Results indicate that hearing threshold levels
      are higher among unscreened noise-exposed and control workers relative to
      screened workers. Analysis of risk factors such as nonoccupational noise
      exposure, medical conditions, and type of industry among unscreened controls
      indicated that these factors were not significantly associated with increased
      mean HTLs or risk of material impairment over and above what is expected due to
      age. Age-specific mean hearing threshold levels (and percentiles of the
      distribution) among the unscreened ONHS control population may be used as a
      comparison population of low-noise exposed white male industrial workers for
      evaluating the effectiveness of hearing conservation programs for workers less
      than 55 years of age. To make valid inferences regarding occupational noise
      induced hearing loss, it is important to use hearing data from reference
      (control) populations that are similar with respect to the degree of subject
      screening, type of work force (blue vs white collar), and the distribution of
      other risk factors for hearing loss.

PMID- 12186038
TI  - Rating, ranking, and understanding acoustical quality in university classrooms.
AB  - Nonoptimal classroom acoustical conditions directly affect speech perception and,
      thus, learning by students. Moreover, they may lead to voice problems for the
      instructor, who is forced to raise his/her voice when lecturing to compensate for
      poor acoustical conditions. The project applied previously developed simplified
      methods to predict speech intelligibility in occupied classrooms from
      measurements in unoccupied and occupied university classrooms. The methods were
      used to predict the speech intelligibility at various positions in 279 University
      of British Columbia (UBC) classrooms, when 70% occupied, and for four instructor
      voice levels. Classrooms were classified and rank ordered by acoustical quality,
      as determined by the room-average speech intelligibility. This information was
      used by UBC to prioritize classrooms for renovation. Here, the statistical
      results are reported to illustrate the range of acoustical qualities found at a
      typical university. Moreover, the variations of quality with relevant classroom
      acoustical parameters were studied to better understand the results. In
      particular, the factors leading to the best and worst conditions were studied. It
      was found that 81% of the 279 classrooms have "good," "very good," or "excellent"
      acoustical quality with a "typical" (average-male) instructor. However, 50 (18%)
      of the classrooms had "fair" or "poor" quality, and two had "bad" quality, due to
      high ventilation-noise levels. Most rooms were "very good" or "excellent" at the
      front, and "good" or "very good" at the back. Speech quality varied strongly with
      the instructor voice level. In the worst case considered, with a quiet female
      instructor, most of the classrooms were "bad" or "poor." Quality also varies with
      occupancy, with decreased occupancy resulting in decreased quality. The research
      showed that a new classroom acoustical design and renovation should focus on
      limiting background noise. They should promote high instructor speech levels at
      the back of the classrooms. This involves, in part, limiting the amount of sound
      absorption that is introduced into classrooms to control reverberation. Speech
      quality is not very sensitive to changes in reverberation, so controlling it for
      its own sake should not be a design priority.

PMID- 12186039
TI  - A model cochlear partition involving longitudinal elasticity.
AB  - This paper addresses the issue of longitudinal stiffness within the cochlea. A
      one-dimensional model of the cochlear partition is presented in which the
      resonant sections are coupled by longitudinal elastic elements. These elements
      functionally represent the aggregate mechanical effect of the connective tissue
      that spans the length of the organ of Corti. With the plate-like morphology of
      the cochlear partition in mind, the contribution of longitudinal elasticity to
      partition dynamics is appreciable, though weak and nonlinear. If the elasticity
      is considered Hookian then the nonlinearity takes a cubic form. Numerical
      solutions are presented that demonstrate the compressive nature of the partial
      differential nonlinear equations and their ability to produce realistic cubic
      distortion product otoacoustic emissions. Within the framework of this model,
      some speculations can be made regarding the dynamical function of the phalangeal
      processes, the sharpness of active cochlear mechanics, and the propogation of
      pathology along the partition.

PMID- 12186040
TI  - Inner hair cell loss and steady-state potentials from the inferior colliculus and
      auditory cortex of the chinchilla.
AB  - Steady-state evoked potentials were measured from unanesthetized chinchillas both
      before and after carboplatin-induced selective inner hair cell loss. Recordings
      were made from both the inferior colliculus (IC) and the auditory cortex (AC).
      The steady-state potential was measured in the form of the envelope following
      response (EFR), obtained by presenting a two-tone stimulus (f1 = 2000 Hz; f2 =
      2020, 2040, 2080, 2160, or 2320 Hz), and measuring the magnitude of the Fourier
      coefficient at the f2-f1 difference frequency. From the IC, precarboplatin, EFR
      amplitude vs difference tone frequency showed a bandpass pattern, with maximum
      amplitude at either 160 or 80 Hz, depending upon stimulus level. Postcarboplatin,
      the preferred difference frequency was 80 Hz for all stimulus levels. From the
      AC, EFR amplitude versus difference tone frequency also showed a bandpass
      pattern, with the maximum amplitude at 80 Hz both pre- and postcarboplatin. EFR
      amplitude from the IC was decreased for some conditions postcarboplatin, while
      the amplitude from the AC showed no significant change.

PMID- 12186041
TI  - Acoustic intensity, impedance and reflection coefficient in the human ear canal.
AB  - The sound power per unit cross-sectional area was determined in human ear canals
      using a new method based on measuring the pressure distribution (P) along the
      length of variable cross-section acoustic waveguides. The technique provides the
      pressure/power reflection coefficients (R/R) as well as the acoustic intensity of
      the nonplanar incident wave (I+, the acoustic input to the ear) and the nonplanar
      outgoing wave (I-, the acoustic output of the ear). Results were compared to the
      classical acoustic impedance (Z) and associated plane-wave power reflection
      coefficient (R(Z)). Performance of the method was investigated theoretically
      using horn equation simulations and evaluated experimentally using pressure data
      recorded in nonuniform waveguides. The method was applied in normal-hearing young
      adults to determine ear-canal position- and frequency-dependence of I(+/-), R,
      and R(Z) using random phase broadband stimuli (1-15 kHz; approximately 75 dB
      SPL). Reflection coefficient (R) measurements at two different locations within
      individual human ear canals exhibited a position dependence averaging deltaR
      approximately 0.1 (over 6 mm distance)--a difference consistent with predictions
      of inviscid acoustics in nonuniform waveguides. Since this position dependence
      was relatively small, an "optimized" position-independent reflection coefficient
      was defined to facilitate practical application and intersubject comparisons.

PMID- 12186042
TI  - Temporal pitch mechanisms in acoustic and electric hearing.
AB  - Two experiments investigated pitch perception for stimuli where the place of
      excitation was held constant. Experiment 1 used pulse trains in which the
      interpulse interval alternated between 4 and 6 ms. In experiment 1a these "4-6"
      pulse trains were bandpass filtered between 3900 and 5300 Hz and presented
      acoustically against a noise background to normal listeners. The rate of an
      isochronous pulse train (in which all the interpulse intervals were equal) was
      adjusted so that its pitch matched that of the "4-6" stimulus. The pitch matches
      were distributed unimodally, had a mean of 5.7 ms, and never corresponded to
      either 4 or to 10 ms (the period of the stimulus). In experiment 1b the pulse
      trains were presented both acoustically to normal listeners and electrically to
      users of the LAURA cochlear implant, via a single channel of their device. A
      forced-choice procedure was used to measure psychometric functions, in which
      subjects judged whether the 4-6 stimulus was higher or lower in pitch than
      isochronous pulse trains having periods of 3, 4, 5, 6, or 7 ms. For both groups
      of listeners, the point of subjective equality corresponded to a period of 5.6 to
      5.7 ms. Experiment 1c confirmed that these psychometric functions were monotonic
      over the range 4-12 ms. In experiment 2, normal listeners adjusted the rate of an
      isochronous filtered pulse train to match the pitch of mixtures of pulse trains
      having rates of F1 and F2 Hz, passed through the same bandpass filter (3900-5400
      Hz). The ratio F2/F1 was 1.29 and F1 was either 70, 92, 109, or 124 Hz. Matches
      were always close to F2 Hz. It is concluded that the results of both experiments
      are inconsistent with models of pitch perception which rely on higher-order
      intervals. Together with those of other published data on purely temporal pitch
      perception, the data are consistent with a model in which only first-order
      interpulse intervals contribute to pitch, and in which, over the range 0-12 ms,
      longer intervals receive higher weights than short intervals.

PMID- 12186043
TI  - Comodulation masking release in consonant recognition.
AB  - Comodulation masking release (CMR) refers to an improvement in the detection
      threshold of a signal masked by noise with coherent amplitude fluctuation across
      frequency, as compared to noise without the envelope coherence. The present study
      tested whether such an advantage for signal detection would facilitate the
      identification of speech phonemes. Consonant identification of bandpass speech
      was measured under the following three masker conditions: (1) a single band of
      noise in the speech band ("on-frequency" masker); (2) two bands of noise, one in
      the on-frequency band and the other in the "flanking band," with coherence of
      temporal envelope fluctuation between the two bands (comodulation); and (3) two
      bands of noise (on-frequency band and flanking band), without the coherence of
      the envelopes (noncomodulation). A pilot experiment with a small number of
      consonant tokens was followed by the main experiment with 12 consonants and the
      following masking conditions: three frequency locations of the flanking band and
      two masker levels. Results showed that in all conditions, the comodulation
      condition provided higher identification scores than the noncomodulation
      condition, and the difference in score was 3.5% on average. No significant
      difference was observed between the on-frequency only condition and the
      comodulation condition, i.e., an "unmasking" effect by the addition of a
      comodulated flaking band was not observed. The positive effect of CMR on
      consonant recognition found in the present study endorses a "cued-listening"
      theory, rather than an envelope correlation theory, as a basis of CMR in a
      suprathreshold task.

PMID- 12186044
TI  - The mid-level hump at 2 kHz.
AB  - Shortening the duration of a Gaussian-shaped 2-kHz tone-pip causes the intensity
      difference limen (DL) to depart from the "near-miss to Weber's law" and swell
      into a mid-level hump [Nizami et al., J. Acoust. Soc. Am. 110, 2505-2515 (2001)].
      For some subjects the size of this hump approaches or exceeds the size reported
      for longer tones under forward masking, suggesting that forward masking might
      make little difference to the DL for very brief probes. To test this hypothesis,
      DLs were determined over 30 to 90 dB SPL for a brief Gaussian-shaped 2-kHz tone
      pip. DLs were obtained first without forward masking, then with the pip placed 10
      or 100 ms after a 200-ms 2-kHz tone of 50 dB SPL, or 100 ms after a 200-ms 2-kHz
      tone of 70 dB SPL. DLs inflated significantly under all forward-masking
      conditions. DLs also enlarged under an 80 dB SPL forward masker at pip delays of
      4, 10, 40, and 100 ms. The peaks of the humps obtained under forward masking
      clustered around a sensation level (SL) that was significantly lower than the
      average SL for the peaks of the humps obtained without forward masking. Overall,
      the results do not support the neuronal-recovery-rate model of Zeng et al. [Hear.
      Res. 55, 223-230 (1991)], but are not incompatible with the Carlyon and Beveridge
      hypothesis [J. Acoust. Soc. Am. 93, 2886-2895 (1993)] that nonsimultaneous
      maskers corrupt the memory trace evoked by the probe.

PMID- 12186045
TI  - Buildup and breakdown of echo suppression for stimuli presented over headphones
      the effects of interaural time and level differences.
AB  - The current study investigates buildup and breakdown of echo suppression for
      stimuli presented over headphones. The stimuli consisted of pairs of 120-micros
      clicks. The leading click (lead) and the lagging click (lag) in each pair were
      lateralized on opposite sides of the midline by means of interaural level
      differences (ILDs) of +/-10 dB or interaural time differences (ITDs) of +/-300
      micros. Echo threshold was measured with an adaptive one-interval, two
      alternative, forced-choice procedure with a subjective decision criterion, in
      which listeners had to report whether they heard a single, fused auditory event
      on one side of the midline, or two separate events on both sides. In the control
      conditions, referred to as the "single" conditions, echo threshold was measured
      for a single click pair, the test pair, presented in isolation. In addition to
      the control conditions, two kinds of test conditions were investigated, in which
      the test pair was preceded by 12 identical conditioning pairs: in the "same"
      conditions, the interaural configuration (ILDs or ITDs) of the conditioning pairs
      was identical to that of the test pair; in the "switch" conditions, the
      interaural configuration of lead and lag was reversed between the conditioning
      pairs and the test pair, in order to produce a switch in the lateralizations of
      the stimuli between the conditioning train and the test pair. No matter whether
      the lateralization of the clicks was produced by ILDs or by ITDs, most listeners
      experienced a buildup of echo suppression in the "same" conditions, manifested by
      a prolongation of echo threshold relative to the respective "single" conditions.
      However, the breakdown of echo suppression was much stronger in the ILD-switch
      than in the ITD-switch conditions. In five out of six listeners, the ITD switch
      had hardly any effect on echo threshold, although the ITDs (+/-300 micros)
      produced roughly the same degree of lateral displacement as the ILDs (+/-10 dB).
      These results suggest that the dynamic processes in echo suppression operate
      differentially in pathways responsible for the processing of interaural time and
      level differences.

PMID- 12186046
TI  - The effects of spatial separation in distance on the informational and energetic
      masking of a nearby speech signal.
AB  - Although many studies have shown that intelligibility improves when a speech
      signal and an interfering sound source are spatially separated in azimuth, little
      is known about the effect that spatial separation in distance has on the
      perception of competing sound sources near the head. In this experiment, head
      related transfer functions (HRTFs) were used to process stimuli in order to
      simulate a target talker and a masking sound located at different distances along
      the listener's interaural axis. One of the signals was always presented at a
      distance of 1 m, and the other signal was presented 1 m, 25 cm, or 12 cm from the
      center of the listener's head. The results show that distance separation has very
      different effects on speech segregation for different types of maskers. When
      speech-shaped noise was used as the masker, most of the intelligibility
      advantages of spatial separation could be accounted for by spectral differences
      in the target and masking signals at the ear with the higher signal-to-noise
      ratio (SNR). When a same-sex talker was used as the masker, the intelligibility
      advantages of spatial separation in distance were dominated by binaural effects
      that produced the same performance improvements as a 4-5-dB increase in the SNR
      of a diotic stimulus. These results suggest that distance-dependent changes in
      the interaural difference cues of nearby sources play a much larger role in the
      reduction of the informational masking produced by an interfering speech signal
      than in the reduction of the energetic masking produced by an interfering noise
      source.

PMID- 12186047
TI  - Broadband sound generation by confined turbulent jets.
AB  - Sound generation by confined stationary jets is of interest to the study of voice
      and speech production, among other applications. The generation of sound by low
      Mach number, confined, stationary circular jets was investigated. Experiments
      were performed using a quiet flow supply, muffler-terminated rigid uniform tubes,
      and acrylic orifice plates. A spectral decomposition method based on a linear
      source-filter model was used to decompose radiated nondimensional sound pressure
      spectra measured for various gas mixtures and mean flow velocities into the
      product of (1) a source spectral distribution function; (2) a function accounting
      for near field effects and radiation efficiency; and (3) an acoustic frequency
      response function. The acoustic frequency response function agreed, as expected,
      with the transfer function between the radiated acoustic pressure at one fixed
      location and the strength of an equivalent velocity source located at the
      orifice. The radiation efficiency function indicated a radiation efficiency of
      the order (kD)2 over the planar wave frequency range and (kD)4 at higher
      frequencies, where k is the wavenumber and D is the tube cross sectional
      dimension. This is consistent with theoretical predictions for the planar wave
      radiation efficiency of quadrupole sources in uniform rigid anechoic tubes. The
      effects of the Reynolds number, Re, on the source spectral distribution function
      were found to be insignificant over the range 2000<Re<20000. The source spectral
      distribution function approximately obeyed a St(-3) power law for Strouhal number
      values St<0.9, and a St-5 power law for St>2.5. The influence of a reflective
      open tube termination on the source function spectral distribution was found to
      be insignificant, confirming the absence of a feedback mechanism.

PMID- 12186048
TI  - Modulation frequency and modulation level owing to vocal microtremor.
AB  - Vocal microtremor designates a normal slow modulation of the vocal cycle lengths
      of speakers who do not suffer from pathological tremor of the limbs and whose
      voices are not perceived as tremulous. Vocal microtremor is therefore distinct
      from pathological vocal tremor. The objective is to report data about the
      modulation frequency and modulation level owing to vocal microtremor. The
      modulation data have been obtained for vowels [a], [i], and [u] sustained by
      normophonic and mildly dysphonic male and female speakers. The results are the
      following. First, modulation frequencies and relative modulation levels do not
      differ significantly for male and female speakers, normophonic and mildly
      dysphonic speakers, as well as for vowel timbres [a], [i], and [u]. Second, the
      typical interquartile intervals of the modulation frequency and modulation level
      are equal to 2.0-4.7 Hz and 0.4%-1.3%, respectively. Third, dissimilarities
      between data reported by different studies are due to different cutoff
      frequencies below which spectral peaks are considered not to contribute to vocal
      microtremor.

PMID- 12186049
TI  - Normalized amplitude quotient for parametrization of the glottal flow.
AB  - Normalized amplitude quotient (NAQ) is presented as a method to parametrize the
      glottal closing phase using two amplitude-domain measurements from waveforms
      estimated by inverse filtering. In this technique, the ratio between the
      amplitude of the ac flow and the negative peak amplitude of the flow derivative
      is first computed using the concept of equivalent rectangular pulse, a
      hypothetical signal located at the instant of the main excitation of the vocal
      tract. This ratio is then normalized with respect to the length of the
      fundamental period. Comparison between NAQ and its counterpart among the
      conventional time-domain parameters, the closing quotient, shows that the
      proposed parameter is more robust against distortion such as measurement noise
      that make the extraction of conventional time-based parameters of the glottal
      flow problematic. Experiments with breathy, normal, and pressed vowels indicate
      that NAQ is also able to separate the type of phonation effectively.

PMID- 12186050
TI  - Learning to perceive speech: how fricative perception changes, and how it stays
      the same.
AB  - A part of becoming a mature perceiver involves learning what signal properties
      provide relevant information about objects and events in the environment.
      Regarding speech perception, evidence supports the position that allocation of
      attention to various signal properties changes as children gain experience with
      their native language, and so learn what information is relevant to recognizing
      phonetic structure in that language. However, one weakness in that work has been
      that data have largely come from experiments that all use similarly designed
      stimuli and show similar age-related differences in labeling. In this study, two
      perception experiments were conducted that used stimuli designed differently from
      past experiments, with different predictions. In experiment 1, adults and
      children (4, 6, and 8 years of age) labeled stimuli with natural /f/ and /[see
      text]/ noises and synthetic vocalic portions that had initial formant transitions
      varying in appropriateness for /f/ or /[see text]/. The prediction was that
      similar labeling patterns would be found for all listeners. In experiment 2,
      adults and children labeled stimuli with initial /s/-like and /[see text]/-like
      noises and synthetic vocalic portions that had initial formant transitions
      varying in appropriateness for /s/ or /[see text]/. The prediction was that, as
      found before, children would weight formant transitions more and fricative noises
      less than adults, but that this age-related difference would elicit different
      patterns of labeling from those found previously. Results largely matched
      predictions, and so further evidence was garnered for the position that children
      learn which properties of the speech signal provide relevant information about
      phonetic structure in their native language.

PMID- 12186051
TI  - Word recognition in competing babble and the effects of age, temporal processing,
      and absolute sensitivity.
AB  - This study was designed to clarify whether speech understanding in a fluctuating
      background is related to temporal processing as measured by the detection of gaps
      in noise bursts. Fifty adults with normal hearing or mild high-frequency hearing
      loss served as subjects. Gap detection thresholds were obtained using a three
      interval, forced-choice paradigm. A 150-ms noise burst was used as the gap
      carrier with the gap placed close to carrier onset. A high-frequency masker
      without a temporal gap was gated on and off with the noise bursts. A continuous
      white-noise floor was present in the background. Word scores for the subjects
      were obtained at a presentation level of 55 dB HL in competing babble levels of
      50, 55, and 60 dB HL. A repeated measures analysis of covariance of the word
      scores examined the effects of age, absolute sensitivity, and temporal
      sensitivity. The results of the analysis indicated that word scores in competing
      babble decreased significantly with increases in babble level, age, and gap
      detection thresholds. The effects of absolute sensitivity on word scores in
      competing babble were not significant. These results suggest that age and
      temporal processing influence speech understanding in fluctuating backgrounds in
      adults with normal hearing or mild high-frequency hearing loss.

PMID- 12186052
TI  - Captive dolphins, Tursiops truncatus, develop signature whistles that match
      acoustic features of human-made model sounds.
AB  - This paper presents a cross-sectional study testing whether dolphins that are
      born in aquarium pools where they hear trainers' whistles develop whistles that
      are less frequency modulated than those of wild dolphins. Ten pairs of captive
      and wild dolphins were matched for age and sex. Twenty whistles were sampled from
      each dolphin. Several traditional acoustic features (total duration, duration
      minus any silent periods, etc.) were measured for each whistle, in addition to
      newly defined flatness parameters: total flatness ratio (percentage of whistle
      scored as unmodulated), and contiguous flatness ratio (duration of longest flat
      segment divided by total duration). The durations of wild dolphin whistles were
      found to be significantly longer, and the captive dolphins had whistles that were
      less frequency modulated and more like the trainers' whistles. Using a standard t
      test, the captive dolphin had a significantly higher total flatness ratio in 9/10
      matched pairs, and in 8/10 pairs the captive dolphin had significantly higher
      contiguous flatness ratios. These results suggest that captive-born dolphins can
      incorporate features of artificial acoustic models made by humans into their
      signature whistles.

PMID- 12186053
TI  - The relative detectability for mice of gaps having different ramp durations at
      their onset and offset boundaries.
AB  - The effect on gap detectability of varying noise fall time (FT) and rise time
      (RT) of the gap boundary ramps was examined in mice using reflex modification
      audiometry, measuring inhibition of acoustic startle reflexes by variously shaped
      gaps just preceding reflex expression. In experiment 1 (n = 12) inhibition
      increased up to near-asymptotic values with longer FT (0, 1, 2, 3, 5, or 10 ms)
      and QT (quiet time, 0 to 13 ms), with a 2:1 trade-off between FT and QT. In
      experiment 2 (n = 24) inhibition increased for any RT above 0 ms (2, 3, 5, or 7
      ms) if QT= 1 ms, but diminished with increased RT when QT = 3 or 8 ms. Enhanced
      detectability for subthreshold gaps by longer ramps results from their extending
      the apparent gap duration. The negative effect of increased RT for threshold gaps
      suggests the importance for gap detection of the stronger neural responses to
      sharp edges at the end of the gap shown previously in the mouse inferior
      colliculus. These effects are specific to gaps: inhibition for fixed (70-dB SPL)
      or varied level pulses (30 to 60 dB) was unaffected by varying the ramped edges
      (experiments 3 and 4, n = 9).

PMID- 12186054
TI  - Auditory temporal resolution in birds: discrimination of harmonic complexes.
AB  - The ability of three species of birds to discriminate among selected harmonic
      complexes with fundamental frequencies varying from 50 to 1000 Hz was examined in
      behavioral experiments. The stimuli were synthetic harmonic complexes with
      waveform shapes altered by component phase selection, holding spectral and
      intensive information constant. Birds were able to discriminate between waveforms
      with randomly selected component phases and those with all components in cosine
      phase, as well as between positive and negative Schroeder-phase waveforms with
      harmonic periods as short as 1-2 ms. By contrast, human listeners are unable to
      make these discriminations at periods less than about 3-4 ms.
      Electrophysiological measures, including cochlear microphonic and compound action
      potential measurements to the same stimuli used in behavioral tests, showed
      differences between birds and gerbils paralleling, but not completely accounting
      for, the psychophysical differences observed between birds and humans. It appears
      from these data that birds can hear the fine temporal structure in complex
      waveforms over very short periods. These data show birds are capable of more
      precise temporal resolution for complex sounds than is observed in humans and
      perhaps other mammals. Physiological data further show that at least part of the
      mechanisms underlying this high temporal resolving power resides at the
      peripheral level of the avian auditory system.

PMID- 12186055
TI  - Abstracts from the 8th International Conference on Alzheimer's Disease and
      Related Disorders. July 20-25, 2002. Stockholm, Sweden.

PMID- 12186056
TI  - Vegetative state patients: Mike Hinchliffe considers the cases.

PMID- 12186057
TI  - In defense of liberal public reason: are slavery and abortion hard cases?

PMID- 12186058
TI  - Brave new ethics: how far would you go to save a child?

PMID- 12186059
TI  - Euthanasia and the right to die: Nancy Cruzan and New Mexico.

PMID- 12186060
TI  - Finding reliable health-care information on the internet.
AB  - The number of Web sites offering health and health-care information has grown
      dramatically over the past several years. However, it can be difficult to tell
      whether or not the information that you find is reliable and accurate. In this
      brief we describe the nature of this issue and offer some practical tips for
      judging reliability when searching for information on the Internet.

PMID- 12186061
TI  - Fabricated man: the dilemma posed by artificial reproductive techniques.

PMID- 12186063
TI  - Rejection of husband's claim to stop wife's abortion.

PMID- 12186064
TI  - Utilizing the bodies of the dead.

PMID- 12186065
TI  - Artificial and transplanted organs: movable parts and the unmoving law.

PMID- 12186067
TI  - Liberty and community in constitutional law: the abortion cases in comparative
      perspective.

PMID- 12186068
TI  - Dignified death: the right to refuse life-sustaining treatment and demand
      continuing comfort care at a private institution.

PMID- 12186069
TI  - Prosecuting pregnant addicts for dealing to the unborn.

PMID- 12186073
TI  - Involuntary outpatient commitment for the chronically mentally ill.

PMID- 12186074
TI  - Personalizing personality: toward a property right in human bodies.

PMID- 12186075
TI  - A matter of life and death: pregnancy clauses in living will statutes.

PMID- 12186076
TI  - Confusion in right to die ideology: impact of ethical decision making for
      treatment of an incompetent client.

PMID- 12186077
TI  - Older clients of questionable competency: making accurate competency
      determinations through the utilization of medical professionals.

PMID- 12186078
TI  - Perry v. Louisiana: medical ethics on death row--is judicial intervention
      warranted?
AB  - The following note considers the complex case of Perry v. Louisiana, in which the
      Louisiana Supreme Court ordered an insane defendant on death row to be medicated
      against his will in order to render him sane, and therefore capable of being
      executed. In so doing the court pit judicial interests in effecting punishment of
      certain murderers against the physician's Hippocratic Oath, "first do no harm."
      In considering this conflict, the note identifies "first do no harm" as a guiding
      principle, explores the societal values underlying this basic principle, and
      concludes the judiciary must provide legal support for this medical ethical
      imperative. Similarly the legal profession must identify its organizing
      principles, its "first do no harm" proscriptions, and consider the application of
      those principles in the context of representing the insane. Some of the conflicts
      confronting the physician in the Perry situation have parallels for the attorney
      representing an insane client. Should the client be medicated in order to proceed
      to trial? Is it in the best interests of the client to remain a prisoner of her
      mental illness rather than to risk the possibility of conviction? How should the
      attorney address the paradoxical reality that a heavily medicated client may
      indeed become more lucid without becoming more competent? By publishing this
      note, the Journal hopes to engender discussion and clarification of the vague and
      sometimes incoherent guidance offered by the Medical Rules of Professional
      Responsibility, the Model Code of Professional Conduct, and the Criminal Justice
      Mental Health Standards for legal work with mentally disturbed clients.

PMID- 12186079
TI  - Clinical sessions and health care ethics.

PMID- 12186080
TI  - Legal/legislative issues in euthanasia and physician-assisted suicide.

PMID- 12186081
TI  - The 1992 ethics code: boon or bane?

PMID- 12186083
TI  - Implications of the 1992 ethics code for the practice of individual
      psychotherapy.
AB  - The current ethics code (American Psychological Association [APA], 1992) provides
      improved standards through increased specificity and proscriptive guidance than
      did the previous code (APA, 1990). Standards 4 and 5 are focused for review in
      this article. Standard 4, Therapy, with additions such as structuring the
      relationship, obtaining informed consent, providing mental health services to
      those served by others, and interrupting and terminating services, are addressed
      and critiqued. Standard 5, Privacy and Confidentiality, is expanded in the
      current code. Some principles are critiqued with regard to their vagueness, their
      tendency to be dilute in terms of power and enforceability, their failure to
      maintain the highest principles for the welfare of clients, and their possible
      advocacy of the welfare of psychologists above that of the clients.

PMID- 12186082
TI  - Implications of the 1992 ethics code for diverse groups.
AB  - Previous renditions of the American Psychological Association's (APA's) code of
      ethics have clearly espoused psychologists' commitment to the ideal of having
      respect for the dignity and worth of the individual human being. The endorsement
      of the goal to protect fundamental human rights has always been highlighted in
      the Preambles of each revision of the code. The current code (APA, 1992) appears
      to have retreated from prioritizing this humanitarian stance. Ethnic minorities,
      women, gay men, and lesbians have reason to be apprehensive about the apparent
      downgrading in importance of psychologists' declaration of respect for the
      dignity and worth of the individual. All previous codes seemed to have been
      formulated from a perspective of protecting consumers. The new code appears to be
      driven by a need to protect psychologists. This article examines the possible
      impact of the shift in traditional priorities on diverse populations.

PMID- 12186084
TI  - Reconsidering the American Psychological Association's policy on sex with former
      patients: is it justifiable?
AB  - This article invites reconsideration of the American Psychological Association's
      policy permitting sexual involvement between therapists and their former patients
      under certain conditions. The article (a) restates 5 major concerns about sex
      after termination that have not been adequately addressed; (b) examines 9 major
      arguments set forth in support of allowing posttermination sexual relationships,
      all of which appear ill-founded, fallacious, or misleading; and (c) describes 6
      obstacles that seem to hinder attempts to create sound legal and professional
      policies in this area.

PMID- 12186086
TI  - Morality in group and family therapies: multiperson therapies and the 1992 ethics
      code.
AB  - Although virtually every psychotherapeutic approach or orientation has adapted
      group and family therapy to its conceptions of psychological dysfunctions and how
      to treat them, levels of training of practitioners in all of these approaches are
      often insufficient to meet the requirements of ethically as well as technically
      responsible conduct of treatment for persons in groups and families. The new
      ethics code (American Psychological Association [APA], 1992) does include a few
      issues specific to multiperson therapies, but other issues critical to the
      competent practice of group and family therapy remain unaddressed. The result can
      be confusing to those applying standards for individual therapy to multiperson
      therapies. It is argued that the classical ethical concerns of psychotherapists,
      informed consent, confidentiality, countertransference reactions, aand intrusions
      of therapist values, require special sensitivity to how they are expressed in
      mulitperson therapies. Practitioners of group and family therapies must be better
      sensitized to the technical distinctions and the associated ethical
      vulnerabilities of the modalities they use. Future planning for revision of the
      APA ethics code should take these factors into account.

PMID- 12186085
TI  - Multiple relationships: does the new ethics code answer the right questions?
AB  - The new "Ethical Principles of Psychologists and Code of Conduct" (American
      Psychological Association, 1992) presented expanded attempts to clarify the
      ethical issues regarding multiple relationships and to provide useful guidance
      for psychologists. This article proposes that the new code fails to address
      adequately two basic questions necessary to provide psychologists with clear
      guidance: (a) What are multiple relationships? and (b) When do multiple
      relationships constitute unethical conduct? The article offers a definition of
      multiple relationships and identifies several dynamics operating within a
      professional relationship that are likely to be adversely affected by the
      imposition of a secondary relationship. Unethical multiple relationships are
      defined. Finally, the article suggests additions to the new code that would
      enhance its utility for psychologists.

PMID- 12186088
TI  - The commerce of professional psychology and the new ethics code.
AB  - The 1992 version of the American Psychological Association's Ethical Principles
      of Psychologists and Code of Conduct brings some changes in requirements and new
      specificity to the practice of psychology. The impact of the new code on
      therapeutic contracts, informed consent to psychological services, advertising,
      financial aspects of psychological practice, and other topics related to the
      commerce of professional psychology are discussed. The genesis of many new
      thrusts in the code is reviewed from the perspective of psychological service
      provider. Specific recommendations for improved attention to ethical matters in
      professional practice are made.

PMID- 12186087
TI  - Testing and assessment ethics for all persons: beginning and agenda.
AB  - The previous American Psychological Association (APA) assessment ethics code
      (APA, 1990) and the new code (APA, 1992) differ in content that is relevant to
      culturally sensitive practices (i.e., culture-specific assessment technologies,
      culture-specific service delivery styles, use of clients' first language, and
      recognition of non-Anglo-American belief systems). The new code falls short in
      areas that are in the process of development or remain controversial. Suggestions
      for implementation and supplementation are included.

PMID- 12186089
TI  - Teaching psychologists and the new APA ethics code: do we fit in?
AB  - The new American Psychological Association (APA) ethics code (APA, 1992) creates
      dilemmas of both image and substance for teaching psychologists. Items specific
      to teaching psychologists reflect housekeeping matters of lesser importance and
      situations over which teaching psychologists have little control. Teachers of
      psychology are sometimes inappropriately grouped with other types of
      psychologists. Freedom of inquiry and communication are curtailed in ambiguous
      ways, and the standards expected of teachers in the academy are set a mediocre
      level. Although the new code contains some improvements over the previous code
      (APA, 1990)--especially in the areas of multiple relationships, prohibitions
      against sex with students, respect for differences among students, and authorship
      rights retained by students--numerous recommendations for future revision are
      strongly recommended.

PMID- 12186090
TI  - Will the new code help researchers to be more ethical?
AB  - A code of ethics has 2 largely incompatible objectives: to set forth enforceable
      minimal standards of conduct and to teach about or invoke ethical conduct. The
      section of the new American Psychological Association code dealing with research
      ethics achieves the former to some degree. However, it neither provides needed
      education in the ethics of research nor states where the reader might turn for
      such information. The code is particularly deficient in the following areas:
      privacy and confidentiality; institutional review boards; deception; debriefing;
      data sharing; and research on marginal populations, on children and adolescents,
      and in organizational contexts. Suggestions are offered for providing a
      bibliographic resource, in hard copy and on-line, that would stimulate
      independent interest, scholarship, education, and research on research ethics.

PMID- 12186091
TI  - Forensic standards in the American Psychological Association's new ethics code.
AB  - The 1992 revision of the American Psychological Association's ethics code
      includes, for the first time, a section devoted to forensic issues. This article
      examines the adequacy with which the Forensic Activities section addresses
      fundamental ethical issues inherent in forensic practices (i.e., being competent
      in forensic practice, dealing with requests for service, providing informed
      consent, providing services, and reporting findings). We conclude that the ethics
      code modestly addresses important forensic ethical issues and that it too often
      is characterized by inconsistencies, insufficient information, omissions, and the
      inappropriate application of the term forensic to general standards not uniquely
      related to forensic practice.

PMID- 12186092
TI  - Explicit ambiguity: the 1992 ethics code as an oxymoron.
AB  - The author reviews the major themes emerging from commentators' reactions to the
      1992 American Psychological Association ethics code and presents his own views as
      well. Commentators agreed that the 1992 code is improved by its increased breadth
      and specific attention to important issues not addressed in the previous code but
      criticized the code for its lack of clarity, its rampant qualifying language, and
      for seeming to protect the profession rather than the public. The author, finding
      the code overly long, detailed, and lawyered, recommends that those who revise
      the code in the 21st century adhere more closely to fundamental moral principles.

PMID- 12186093
TI  - Researching the effects of confidentiality law on patients' self-disclosures.
AB  - We hypothesized that conflicting research findings on the effects that
      confidentiality laws have on patients' self-disclosure reflect the fact that
      privacy is important only to some patients in some circumstances. Instead of
      asking whether privacy is always important, we posed the following question: What
      factors determine whether privacy is important? With 42 outpatients we found that
      self-disclosures about sensitive issues (e.g., child abuse, drug abuse) during
      intake were determined partly by how legally informed patients were and partly by
      how relevant and consequential the law was to their cases.

PMID- 12186095
TI  - Dentists, physicians look at HIV patients with different eyes.

PMID- 12186097
TI  - Hidden sacrifice: for every transgenic mouse, tens more are consigned to an early
      grave.

PMID- 12186098
TI  - It's a pig's life.

PMID- 12186100
TI  - Stop that clock: the menopause is dead, long live the menopause.

PMID- 12186101
TI  - Hope on ice: reversing the menopause may be tougher than we think.

PMID- 12186102
TI  - Pill power.

PMID- 12186103
TI  - Retroperitoneal leiomyosarcoma and enlarged epididymis associated with a positive
      pregnancy test.
AB  - A 57-year-old man presented with a 1-month history of progressive abdominal pain
      and weight loss. A palpable, nonpulsatile, firm abdominal mass was felt below the
      xiphisternum down to the pelvis. A pregnancy test performed on a urine sample was
      positive. Testicular examination and testicular ultrasound were normal.
      Computerized tomography of the abdomen revealed a retroperitoneal mass measuring
      30 x 21 x 13 cm. Serum beta-human chorionic gonadotropin (beta-HCG) was serially
      increased (19.71-22.71 mIU/mL). Results of histopathology tests confirmed the
      diagnosis of leiomyosarcoma. The level of serum beta-HCG decreased to < 0.2
      mlU/mL after chemotherapy. Beta-HCG is usually increased in germ-cell tumors but
      few reports in the literature describe beta-HCG-secreting leiomyosarcomas. The
      incidence of increased levels of beta-HCG in sarcomas in general, and its
      potential role as a tumor marker, is not known. A simple urine pregnancy test may
      be done in the work-up of abdominal masses.

PMID- 12186104
TI  - Angiotensin-converting enzyme inhibitor angioedema of the intestine: a case
      report and review of the literature.
AB  - Visceral angioedema is a rare complication of angiotensin-converting enzyme (ACE)
      inhibitor use. To date, 15 cases have been reported in the literature. Common
      presentation is that of a middle-aged woman with abdominal pain, emesis, and
      diarrhea who has recently begun taking an ACE inhibitor. Signs include
      leukocytosis, ascites, and edematous small bowel seen on computed tomography.
      Diagnosis is elusive, and frequently invasive procedures, including surgery, are
      pursued. These can be avoided if the astute physician recognizes the association
      and withdraws the offending medication. We present the typical diagnostic dilemma
      faced in the evaluation of a patient with ACE inhibitor angioedema of the
      intestine, and review the current available literature.

PMID- 12186105
TI  - Severe graves ophthalmopathy accompanied by HTLV-1-associated uveitis (HAU) and
      anti-neutrophil cytoplasmic antibody-related vasculitis: a case report and a
      review of the literature of HAU with Graves disease.
AB  - A 50-year-old woman was admitted because of severe exophthalmos associated with
      Graves disease. She underwent methimazole (MMI) and methylprednisolone pulse
      therapy against exophthalmos. She noticed photophobia and blurred vision 3 weeks
      after the start of pulse therapy and she was diagnosed as having uveitis.
      Methylprednisolone pulse therapy was performed again for both exophthalmos and
      uveitis, followed by daily administration of 20 mg of prednisolone and
      instillation of betamethasone for 2 weeks and the uveitis was improved. Western
      blot analysis confirmed that human T lymphotropic virus type 1 (HTLV-1) antibody
      was present in her serum. Propylthiouracil was substituted for MMI and HTLV-1
      associated uveitis (HAU) has not recurred. Six months after the beginning of
      administration of PTU, anti-neutrophil cytoplasmic antibody-related vasculitis
      developed in the patient. We review 43 cases of HAU with Graves disease,
      including the present case, in the literature. Only 2 of 27 cases (except unknown
      cases) (7.4%) had Graves ophthalmopathy. To the best of our knowledge, there has
      been no investigation of HAU and Graves ophthalmopathy.

PMID- 12186106
TI  - Modern academic medicine.

PMID- 12186107
TI  - Presentation of the Southern Society for Clinical Investigation 2002 Founders'
      Medal to Dr. James B. Dale.

PMID- 12186108
TI  - Southern Society for Clinical Investigation Founders' Medal recipient's address.

PMID- 12186109
TI  - Southern Society for Clinical Investigation: constitution, bylaws, and
      amendments.

PMID- 12186110
TI  - Insulin resistance syndrome and left ventricular mass in healthy young people.
AB  - BACKGROUND: Findings of atherosclerotic plaques in adolescents, in the context of
      current epidemics of obesity and type 2 diabetes in youth, demand investigation
      into early cardiovascular risk development. Left ventricular hypertrophy has been
      linked to hypertension, obesity, and insulin resistance. METHODS: Insulin
      resistance syndrome characteristics (fasting glucose and insulin; systolic blood
      pressure; waist girth) were measured in 70 normotensive, normoglycemic young
      people (60% male, 62% black; included 13 twin pairs; age mean +/- SD, 19 +/- 2.6
      years). Left ventricular mass indexed by height (2.7) (LVMI) was obtained via
      ultrasound. Twin pairs were clustered to satisfy the assumption for independent
      observations. RESULTS: LVMI was regressed on insulin after controlling for race,
      gender, and systolic blood pressure. Insulin was a significant (P = 0.02)
      independent predictor of LVMI (R(2)change = 0.09, P < 0.01). Waist girth
      accounted for an additional 4% variance of LVMI (P = 0.05). A one-factor model
      comprising waist (factor loading = 0.83), insulin (0.59), glucose (0.42), and
      LVMI (0.46) showed good fit [chi2(2) = 0.41, P = 0.81; root-mean-square error of
      approximation = 0.0]. CONCLUSIONS: A subclinical metabolic syndrome is detectable
      early in life, before abnormal fasting glucose or high blood pressure appear.
      Evidence of excessive load on the heart is associated with the metabolic syndrome
      even after accounting for the effects of race, gender, and blood pressure.
      Cardiac structure seems as closely associated with this syndrome as fasting
      glucose level. Based on this evidence, we propose that increased left ventricular
      mass is a part of insulin resistance syndrome and adds to the need for preventive
      public health measures to improve health behaviors and cardiovascular risk status
      in US youth.

PMID- 12186111
TI  - Effects of cocaine and alcohol alone and in combination on cardiovascular
      performance in dogs.
AB  - BACKGROUND: With the proliferation of cocaine abuse, increased incidence of
      catastrophic cardiovascular events such as angina pectoris, myocardial
      infarction, ventricular arrhythmias, or sudden death are reported. Many of these
      patients also drink alcohol before and after cocaine use, leading to a high
      frequency of simultaneous exposure to both the drugs. Cocaine and ethanol's
      independent effects on cardiodynamics are well documented, but their combined
      effects on complete cardiovascular hemodynamics remain unknown. Are effects
      additive, synergistic, or antagonistic? METHODS: Sixteen dogs were instrumented
      to pass cardiac catheters into right and left ventricles. After they recovered
      from the effects of anesthesia, experiments were performed. In phase I, 18
      experiments (6 dogs) established the dose by dose response curve. In phase II and
      III, another 10 dogs, subjected to 30 experiments, were given i.v. cocaine
      followed by ethanol and vice versa to study their effects on hemodynamics and
      coronary flow reserve. RESULTS: Phase I: doses of cocaine (2 mg/kg) and ethanol
      (400 mg/kg) were established. Phase II: cocaine increased heart rate, blood
      pressure and dP/dt but ethanol administered after cocaine attenuated these
      effects [first derivative of the left ventricular pressure (dP/dt) < 2052 +/- 104
      from 2614 +/- 110 mm Hg/sec; P < 0.04)]. Phase III: alcohol mildly increased
      hemodynamic parameters. Cocaine's administration as the second drug had
      synergistic excitatory effects (dP/dt > 3300 +/- 160 from 2854 +/- 142 mm Hg/sec;
      P < 0.004). CONCLUSION: Cocaine increased heart rate, blood pressure, and dP/dt
      but reduced CFR. Alcohol mildly increased the hemodynamic variables and CFR.
      Combined cocaine and alcohol attenuated the excitatory effects of cocaine
      significantly. A reversed drug combination (ie, alcohol then cocaine) generated
      synergistic excitatory effects on the cardiovascular system of the dogs.

PMID- 12186112
TI  - Dementia: when is it not Alzheimer disease?
AB  - The advent of symptomatic therapies for Alzheimer disease has placed increasing
      emphasis on early diagnosis of the dementia syndrome and its various types. This
      article reviews the definition and epidemiology of the condition that affects up
      to 50% of all Americans over the age of 80. Also discussed are the main causes of
      dementia, focusing on those that are not Alzheimer disease and a diagnostic
      approach that is based on guidelines recently published by the American Academy
      of Neurology.

PMID- 12186113
TI  - Erdheim-Chester disease with prominent pericardial involvement: clinical,
      radiologic, and histologic findings.
AB  - Erdheim-Chester disease (ECD) is a rare form of non-Langerhans cell
      histiocytosis. Herein we describe documented skeletal and pericardial involvement
      by ECD producing cardiac tamponade in a 30-year-old woman. The diagnosis of ECD
      was established by histopathology, immunocytochemistry, and by radiologic studies
      demonstrating diffuse, bilateral, symmetrical osteosclerosis of the long bones,
      sparing the epiphyses and axial skeleton. Scintography using methyl diphosphonate
      showed increased uptake in involved bone. The patient presented with jaundice and
      hepatic congestion produced by cardiac tamponade. Pericardial biopsy revealed
      xanthogranulomatous lesions comprised of foamy and lipid-laden macrophages,
      multinucleated giant cells, monocytes, and lymphocytes in a mesh of fibrosis.
      Immunohistochemical staining was positive for CD68 and negative for CD1a,
      consistent with ECD rather than with the much more common Langerhans cell form of
      histiocytosis.

PMID- 12186114
TI  - Yoga practices and hypertension.

PMID- 12186115
TI  - Therapeutic potential of yoga practices in modifying cardiovascular risk profile
      in middle aged men and women.
AB  - AIMS OF STUDY: To study effect of yoga on the physiological, psychological well
      being, psychomotor parameter and modifying cardiovascular risk factors in mild to
      moderate hypertensive patients. METHODS: Twenty patients (16 males, 4 females) in
      the age group of 35 to 55 years with mild to moderate essential hypertension
      underwent yogic practices daily for one hour for three months. Biochemical,
      physiological and psychological parameters were studied prior and following
      period of three months of yoga practices, biochemical parameters included, blood
      glucose, lipid profile, catecholmines, MDA, Vit. C cholinesterase and urinary
      VMA. Psychological evaluation was done by using personal orientation inventory
      and subjective well being. RESULTS: Results showed decrease in blood pressure and
      drug score modifying risk factors, i.e. blood glucose, cholesterol and
      triglycerides decreased overall improvement in subjective well being and quality
      of life. There was decrease in VMA catecholamine, and decrease MDA level
      suggestive decrease sympathetic activity and oxidant stress. CONCLUSION: Yoga can
      play an important role in risk modification for cardiovascular diseases in mild
      to moderate hypertension.

PMID- 12186116
TI  - Response of regimens of insulin therapy in type 2 diabetes mellitus subjects with
      secondary failure.
AB  - OBJECTIVE: To find the response of various regimen of combination therapy
      (Insulin and Glibenclamide) in type 2 diabetes mellitus subjects who failed to
      respond to maximum doses of glibenclamide (GBC) plus phenformin. METHODS: A total
      of 188 subjects with secondary sulfonylurea failure who failed to respond to
      maximum doses of GBC and phenformin were randomised to receive one of the four
      regimens. Group A (50 patients) received two doses of insulin; Group B (49
      patients) received two doses of insulin and GBC 20 mg/day; Group C (43 patients)
      received morning dose of insulin with GBC 20 mg/day; and Group D (46 patients)
      received evening dose of insulin with GBC 20 mg/day. Insulin dose was adjusted to
      achieve an acceptable blood glucose control. Control of diabetes was revaluated
      at three months post-treatment period. RESULTS: Age, duration of diabetes,
      weight, body mass index (BMI) and biochemical parameters were comparable in all
      four groups at admission. Dose of insulin was 0.83 +/- 0.07, 0.86 +/- 0.06, 0.46
      +/- 0.04 and 0.39 +/- 0.03 units/Kg/day in groups A, B, C and D, respectively.
      Comparing groups A and B, we found that the dose of insulin (IU/kg/day) required
      to achieve acceptable fasting blood glucose (FBG) did not differ significantly.
      Similarly, comparison between Groups C and D did not reveal any significant
      difference in insulin dose. Mean hospital stay required to achieve an acceptable
      FBG was 8.42 +/- 0.34, 11.95 +/- 1.11, 8.59 +/- 0.61 and 7.10 +/- 0.48 days in
      groups A, B, C and D, respectively (p = 0.013). On comparing the four treatment
      regimens, at three months follow-up, there was a significant increase in
      bodyweight in Group C; also there was an increase in fasting blood glucose in all
      the groups except in Group D. CONCLUSIONS: Continuation of GBC in type 2 diabetes
      mellitus subjects who fail to respond to maximum doses of GBC plus phenformin and
      who need two doses of insulin for control has no added advantage over giving
      insulin alone. In subjects controlled on a single dose of insulin with
      glibenclamide it is preferable to give an evening dose rather than a morning
      dose.

PMID- 12186117
TI  - Percutaneous treatment of hepatic hydatid cysts using hypertonic saline.
AB  - BACKGROUND: Due to improvements in imaging techniques and immunodiagnostic
      methods there has been a spurt of cases of hepatic hydatidosis. Till now surgical
      management in the form of marsupialization and tube drainage, omentoplasty or
      hepatectomy was the mainstay of treatment. Recently treatment options have
      improved considerably after introduction of the PAIR (precutaneous aspiration,
      injection of scolicidal agent and reaspiration) procedure. In this study we
      report the results of ultrasound guided PAIR procedure in 39 hepatic hydatid
      cysts. METHOD: All patients with hepatic hydatid cysts underwent the PAIR
      procedure under ultrasound guidance. The scolicidal agent used was 20% hypertonic
      saline. Type I and II (n=24) cysts were managed by precutaneous aspiration while
      type III and IV showing a multiloculated or pseudotumour appearance (n=15) cysts
      were managed by the percutaneous placement of a Malecot's catheter which was
      removed after 3-7 days. RESULTS: All patients responded to the PAIR procedure.
      The commonest ultrasonographic appearance in hepatic hydatid cyst patients was a
      solitary uniloculated cyst with prominent back wall echoes in the right lobe of
      the liver. The complications encountered were in the form of mild hypotension
      (two cases), urticaria in one patient and severe hypotension leading to shock in
      one case. CONCLUSIONS: The PAIR procedure was found to be effective, cheap and
      safe in the non-surgical management of hepatic hydatid cysts.

PMID- 12186118
TI  - Clinical implications of viral activity in dual infection with hepatitis B and C
      in chronic liver disease.
AB  - BACKGROUND: There is limited information on the clinical and biochemical profile
      of chronic liver disease due to dual infection with hepatitis B virus (HBV) and
      hepatitis C virus (HCV) infection. There are variable reports on the severity of
      liver disease in dual infections. This is important, from clinical and
      therapeutic point of view. The present study analyzes liver disease in dual
      infections as compared to HBV and HCV infection present alone. MATERIAL AND
      METHODS: Out of 186 histologically proven non-alcoholic chronic liver disease
      patients, 30 (16.1%) were serologically diagnosed to be HBV and HCV dual
      infection (Group A, n=30). The clinical profile of these patients was compared
      with consecutively seen HBV related (Group B, n=30) and HCV related chronic liver
      disease (Group C, n=30) patients. Patients with dual infection were further
      grouped based on predominant HBV or HCV viral activity. RESULTS: Patients with
      dual infection were younger than those with chronic HCV infection (38.4 +/- 14.4
      vs. 45.9 +/- 14.7 years, p < 0.05); with male predominance (p=0.06). Patients
      with chronic HCV infection more often presented with low-grade fever than dual
      infection group (60% vs. 30%, p < 0.05). Ascites and variceal bleeding were
      common presentations of HBV related cirrhosis. Patients with dual infection had
      significantly more deranged liver functions. The duration of illness was shorter
      in these patients compared with chronic HCV (2.9 +/- 1.6 vs. 7.3 +/- 1.4 year, p
      < 0.05). When patients with dual infection were subgrouped on HBV DNA and HCV RNA
      positivity, there was a tendency for increased biochemical derangement with
      active HBV infectionity. CONCLUSIONS: Our results highlight the fact that
      patients with HBV and HCV dual infection related chronic liver disease have a
      more aggressive course. There is a tendency for a more severe liver disease when
      HBV is active in the dual infection group.

PMID- 12186119
TI  - Lipoprotein(a) in South Indian type 2 diabetic subjects in relation to diabetic
      vascular complications.
AB  - OBJECTIVES: Lipoprotein(a) [LP(a)] has been reported to be an independent risk
      factor for coronary artery disease (CAD). However, its relationship with other
      vascular complications is not clear. The aim of the study was to determine the
      relation of lipoprotein(a) with micro- and macrovascular complications seen in
      type 2 diabetic patients. METHODS: We studied 725 type 2 diabetic patients with
      and without diabetic complications at the MV Diabetes Specialities Centre,
      Chennai. The mean age of the study group was 54 +/- 10 years and 70% were males.
      Diabetic complications viz retinopathy, proteinuria, peripheral vascular disease
      and coronary artery disease were diagnosed using standardized definitions.
      Lipoprotein(a) levels were measured using enzyme linked immunosorbant assay
      (ELISA). Since the frequency distribution of Lp(a) was skewed Lp(a) values were
      log transformed and geometric mean was used for statistical analysis. RESULTS:
      The mean Lp(a) level of patients with any vascular complication was significantly
      higher compared to the subjects without any complications. Multiple logistic
      regression analysis revealed that lipoprotein(a) had as independent association
      with CAD (Odds Ratio -1.16, p=0.04) and proteinuria (Odds Ratio -1.69, p <
      0.001). The association of Lp(a) with retinopathy and PVD turned out to be non
      significant when CAD and proteinuria was introduced as cofactors in the
      regression model. CONCLUSION: Lp(a) concentrations are found to be higher in
      those with CAD and proteinuria. There appears to be no association between Lp(a)
      and retinopathy or PVD in South Indian type 2 diabetic patients.

PMID- 12186120
TI  - Open label, randomised, comparative phase III safety and efficacy study with
      conventional amphotericin B and liposomal amphotericin B in patients with
      systemic fungal infection.
AB  - OBJECTIVE: To compare conventional amphotericin B (c-amp B) and liposomal
      amphotericin B (L-AMP-LRC-1-India) in patients with systemic fungal infection in
      open, randomized, comparative, laboratory blind, phase III safety and efficacy
      study. MATERIAL AND METHODS: Formulation of liposomal amphotericin B - L-AMP-LRC
      1, containing natural phospholipids, was prepared and tested at the Department of
      Clinical Pharmacology, Seth GS Medical College and KEM Hospital, Mumbai, India.
      Patients suffering from proven systemic fungal infection, were treated with c-amp
      B or L-AMP-LRC-1 with 17 patients in each group. Data was compared for the safety
      and efficacy. RESULTS:  SAFETY: L-AMP-LRC-1 was better tolerated than c-amp B.
      Out of the 695 infusions of c-amp B fever occurred on 25.04% occasions in 68.42%
      patients, while it occurred on 2.09% occasions out of 767 infusions (in 30.43%
      patients of L-AMP-LRC-1. Chills occurred on 16.83% and 1.17% occasions after c
      amp B and liposomal amphotericin B respectively. Other adverse effects observed
      on 0.2-5% of occasions were: headache, nausea, vomiting, palpitation and
      dizziness occurring more frequently in c-amp B group. The L-AMP-LRC-1 did not
      cause bronchospasm at 1 mg/kg dose in a patient who developed bronchospasm to 0.1
      mg/kg dose of c-amp B. The L-AMP-LRC-1 was found to be less nephrotoxic than c
      amp B and could be administered to patients who had renal problems or had
      undergone renal transplant. L-AMP-LRC-1 caused less hypokalemia than c-amp B.
      Effficacy: 17/17 patients in L-AMP-LRC-1 group and 14/17 in c-amp B group had
      complete response (100% and 82.35% response rate). The number of infusions and
      dose of amphotericin B and L-AMP-LRC-1 used were similar and required
      individualization of duration of treatment (in cases where response to fixed
      duration was not observed). All the patients were treated with 0.5 to 1.0
      mg/kg/day dose of L-AMP-LRC-1 (except one patient required 2 mg/kg dose). This is
      markedly different from other marketed liposome and lipid formulations, which are
      recommended at higher (3-5 mg/kg) doses every day. At the same time L-AMP-LRC-1
      being prepared from naturally occurring lipids is expected to cost at least one
      third of the marketed formulation. Thus cost of every day treatment would be very
      much less compared to other delivery systems. Thus L-AMP-LRC-1 will be an
      economical and safe treatment option available to the physicians for the
      treatment of systemic fungal infection.

PMID- 12186121
TI  - Changing trends in clinical presentations in referred human immunodeficiency
      virus infected persons in Pune, India.
AB  - AIMS: To study profile and trends of clinical presentations among human
      immunodeficiency virus (HIV) infected individuals seen in a HIV Reference Clinic
      in Pune. METHODOLOGY: In a cross-sectional study, 3574 subjects were seen at a
      HIV Clinic in Pune from January 1997 to December 1999. Data on clinical
      presentation of 2801 (78.4%) HIV seropositive subjects were evaluated. RESULTS:
      Clinical conditions like oral thrush, tuberculosis, skin rash and sexually
      transmitted diseases showed decreasing trends during the three years study period
      (p=0.03, 0.02, < 0.01 and < 0.01, respectively). Conversely a significant
      increase in the number of asymptomatic HIV positive persons at the time of
      detection was observed over the same period (p < 0.01). CONCLUSION: Temporal
      change in the clinical presentations in the HIV positive persons referred to our
      clinic probably reflects increased awareness and a high index of suspicion among
      clinicians. Early diagnosis of HIV infection in asymptomatic phase might help the
      clinicians to make timely decisions on prescribing chemoprophylaxis for
      prevention of opportunistic infections and to take appropriate measures for
      prevention of secondary HIV transmission to the uninfected sex partners/spouses.

PMID- 12186122
TI  - Autologous transfusion--a viable alternative.
AB  - INTRODUCTION: Transfusion of blood carries an inherent threat of immunological
      complications and an ever-increasing risk of transfusion transmitted diseases. A
      safer alternative to these potential dangers is autologous transfusion. This
      relatively simple and innocuous procedure strives to achieve the goal of 'Safe
      Blood', and can be practised easily in the peripheral hospitals. MATERIAL AND
      METHODS: A study was conducted to evaluate this facet of transfusion medicine, in
      a Services Zonal Hospital, for the period January, 1998 to July, 2000. RESULTS: A
      total of 45 pre-operative autologous collections were undertaken during this
      duration. By conducting regular interactive programmes with the healthcare
      workers and the patients, the rate of autologous transfusion vis-a-vis total
      transfusion increased from 0.34% in 1998 to 13.83% till July, 2000. CONCLUSION:
      It is recommended that there should be vigorous participation at all levels in a
      hospital, under the auspices of an active hospital transfusion committee, to make
      this procedure more popular and more acceptable in today's scenario. This will
      not only reduce the load of allogenic transfusion, but will also help to diminish
      the potential hazards associated with blood transfusion.

PMID- 12186123
TI  - Hematopoietic growth factors in drug-induced agranulocytosis.
AB  - Drug-induced agranulocytosis (DIA) is a potentially fatal disorder. Hematopoietic
      growth factors have been used in the treatment of DIA. We report nine cases of
      DIA treated with granulocyte macrophage - colony stimulating factor (GM-CSF) in a
      dose of 300 microg/day. All the patients had evidence of systemic infection. Mean
      time to reach an absolute neutrophil count of 0.5 x 10(9)/L was three days. One
      patient succumbed to the disease. The cause of death was multiorgan failure. No
      adverse events were observed with GM-CSF. We conclude that hematopoietic growth
      factors are useful in shortening the period of neutropenia and reducing morbidity
      and mortality in these patients.

PMID- 12186125
TI  - Medical personalities on stamps. J.M. Charcot (1825-1893)--postal stamp of France
      -1960.

PMID- 12186124
TI  - Comparison of the efficacy and safety of pravastatin and simvastatin in heart
      transplantation.
AB  - AIMS: Data on the safety and efficacy of HMG CoA reductase inhibitors in managing
      dyslipidemia in heart transplant recipients is inadequate. We undertook this
      study to evaluate the comparative safety and efficacy of simvastatin and
      pravastatin in lowering lipids in heart transplant recipients. METHODOLOGY: Forty
      eight patients (38 males) who received heart transplantation between 1995 and
      1997, and who had no contraindications to statin therapy or history of myopathy
      were randomized to receive either pravastatin (n=24) or simvastatin (n=24) for
      six months. Detailed fasting lipid profiles, hepatic function tests, and serum
      creatinine phosphokinase were obtained regularly. Baseline and six month
      characteristics were compared using the unpaired student t test for continuous
      variables and Chi-square analysis or Fisher's exact test, as appropriate.
      RESULTS: Baseline total cholesterol levels, LDL cholesterol levels, HDL
      cholesterol levels, and triglyceride levels were similar in the two groups. At
      six months, the total cholesterol, LDL cholesterol, and triglyceride levels were
      greatly reduced in both groups, with greater reductions in the simvastatin group
      than in the pravastatin group. Only modest increases were noted in HDL
      cholesterol levels in the two groups. No significant adverse effects were noted,
      and no complications with drug withdrawals occurred. Patient compliance exceeded
      97%. CONCLUSION: Simvastatin and pravastatin are safe and very effective in total
      cholesterol and LDL cholesterol lowering in heart transplant recipients, with
      simvastatin being more efficacious than pravastatin in lipid lowering in this
      group of patients.

PMID- 12186126
TI  - Pictorial CME. A case of encephalitis.

PMID- 12186127
TI  - Can fall in anti-H. pylori IgG titres indicate eradication?
AB  - At present, it is not clear whether a fall in serological titres of anti-H.
      pylori IgG can be used for confirming eradication. A prospective study was
      conducted using varying cut-off levels from (10% to 50%) fall in anti-H. pylor
      IgG levels as a test of eradication in comparison to urease and histology. It was
      found that sensitivity was highest using a 10% cut-off but specificity wasvery
      low. Increasing cut-off values increased specificity but resulted in declining
      sensitivity without altering accuracy much. It appears that in the short term,
      percentage decline in serological titres can at best serve as a crude test of
      eradication.

PMID- 12186128
TI  - What a machine--this human body?

PMID- 12186129
TI  - Geriatric medicine programs in India: has the time arrived?
AB  - Aging trends in India and the world over are burdening society with the health
      care and economic problems resulting from an older population. With this in mind,
      countries are preparing themselves to face the challenges of meeting this burden.
      India with its huge population and improving life-expectancy should be no
      exception. The task involves preparation in healthcare to take care of the
      elderly and train a new generation of physicians in geriatric medicine. The
      review attempts to address some of these issues and makes pertinent
      recommendations, based on the author's own experiences in developing a large
      geriatric program with all necessary components in the last decade.

PMID- 12186130
TI  - Novel diagnostic and therapeutic approaches in medullary carcinoma of thyroid:
      emerging role of nuclear medicine in its management.

PMID- 12186131
TI  - Aetiopathogenesis and management of diabetic neuropathy.

PMID- 12186132
TI  - Vocal cord dysfunction masquerading as bronchial asthma.
AB  - Vocal cord dysfunction (VCD) is a relatively rare condition that may mimic asthma
      or upper airway obstruction. In contrast to initial reports, recent work
      emphasizes that patients with VCD often may have both asthma and VCD
      concurrently. VCD presents a formidable diagnostic challenge. Spirometry often
      gives variable results. The diagnosis is confirmed at direct laryngoscopy by
      observing abnormal vocal cord movements without other pathologic processes.
      Therapy of VCD involves removal of unnecessary medications, efforts to minimize
      vocal cord irritation, and aggressive speech therapy. In selected cases,
      anxiolytic medications and psychiatric consultation may be beneficial.

PMID- 12186133
TI  - Gerbode's defect--a rare type of ventricular septal defect.
AB  - We report on an elderly lady in the sixth decade of life with congenital
      Gerbode's defect who refused surgery. She has atrial fibrillation, massive
      cardiomegaly and repeated episodes of lower respiratory tract infection.

PMID- 12186134
TI  - Typhoid hepatitis.
AB  - Though typhoid fever is quite common, typhoid hepatitis is a very rare entity
      which may have a variety of presenting features similar to other more common
      conditions. One case of typhoid hepatitis is reported here because of its ratity.

PMID- 12186135
TI  - Bilateral haemorrhagic cerebellar infarction following honey bee sting.

PMID- 12186136
TI  - Posterior leukoencephalopathy in a girl with acute haemorrhagic
      leukoencephalitis.
AB  - In children, posterior leukoencephalopathy is frequently associated with
      hypertensive encephalopathy, anticancer chemotherapy, treatment with
      immunosuppressive drugs in patients with organ transplantation, transfusion or
      human immunodeficiency virus infection. Posterior leukoencephalopathy in these
      children appears as a complicating illness and resolves once precipitating factor
      (e.g. cancer chemotherapy) is removed. Here we are reporting a fatal case of
      acute haemorrhatic leukoencephalitis in a 13 year old girl, imaging abnormalities
      are also suggestive of posterior leukoencephalopathy. Posterior
      leukoencephalopathy in our patient possibly, is a part of post-infectious
      haemorrhagic leukoencephalitis, rather than because of ischaemia or cerebral
      oedema secondary either to abrupt increase in blood pressure or following
      administration of immunosuppressive drugs.

PMID- 12186137
TI  - Pneumocystis carinii pneumonia: role of high resolution computed tomography.
AB  - Pneumocystis carinii (PC) is a common opportunistic infection in renal transplant
      recipients and requires an early diagnosis for its successful treatment. For its
      definitive diagnosis PC needs to be demonstrated in bronchoalveolar lavage (BAL)
      fluid. At times BAL may not be possible or get delayed. In such conditions
      typical appearances seen on high resolution CT of the chest help in early
      diagnosis of PC pneumonia (PCP). This easily performed procedure helped in early
      diagnosis of PCP in two patients.

PMID- 12186138
TI  - Trichinosis of psoas muscle.
AB  - There are isolated case reports of Trichinella spiralis infestation in animals
      from India. We report the first case in man from India. The nematode was
      discovered incidentally during drainage of psoas abscess.

PMID- 12186139
TI  - Malignant pheochromocytoma with cutaneous metastases presenting with hemolytic
      anemia and pyrexia of unknown origin.
AB  - We describe a 43 year old female who presented with pyrexia of unknown origin
      associated with Coomb's negative hemolytic anemia and impaired liver function
      tests of six months duration. A routine abdominal computerised tomographic scan
      showed a mass in the left adrenal which was excised at laparotomy and
      histologically diagnosed as pheochromocytoma. The hemolysis continued to worsen
      with development of resistance to steroid therapy. Subsequently she developed
      multiple firm to hard painless cutaneous nodules which were aspirated for
      cytologic examination. The cytology picture was that of a neuroendocrine tumour
      with cell morphology similar to that of the adrenal pheochromocytoma. Such an
      association of hemolytic anemia, pyrexia and cutaneous metastases in a case of
      malignant pheochromocytoma has not been described earlier in the medical
      literature.

PMID- 12186140
TI  - Early non-hodgkin lymphoma (null-cell type) with uncommon presentation in renal
      transplant recipient.

PMID- 12186141
TI  - Oculomotor palsy associated with hepatitis E infection.

PMID- 12186142
TI  - Homozygous familial hypercholesterolemia.

PMID- 12186143
TI  - Hypothyroidism presenting as sleep apnoea hypopnoea syndrome.

PMID- 12186144
TI  - Haematopoietic growth factors in chloramphenicol-induced agranulocytosis.

PMID- 12186145
TI  - Posterior interosseous nerve injury due to monkey bite.

PMID- 12186146
TI  - Accidental self injection with Freund's complete adjuvant.

PMID- 12186147
TI  - Hyperfibrinogenemia in patients of diabetes mellitus in relation to glycemic
      control and urinary albumin excretion rate.

PMID- 12186148
TI  - Drug advertisements in Indian medical journals: total lack of information:
      requires improvement.

PMID- 12186149
TI  - Spinal muscular atrophy.

PMID- 12186150
TI  - Non-allopathic systems of medicine--time to reflect and act.

PMID- 12186151
TI  - Homocysteine and its role in the pathogenesis of atherosclerotic vascular
      disease.
AB  - Homocysteine has been recently recognised as a risk factor for atherosclerotic
      vascular disease. Numerous studies have studied adverse influence of homocysteine
      on endothelial cells, vascular smooth muscle cells, connective tissue,
      interactions with plasma lipoproteins, clotting factors and platelets. It has
      been suggested that endothelial damage is mediated by hydrogen peroxide, a by
      product of auto-oxidation of homocysteine. Human studies have shown that high
      levels of homocysteine are associated with impaired endothelial dependent
      vasodilatation in healthy subjects indicating that the bio-availability of nitric
      oxide (NO) is decreased in those with hyper-homocysteinemia. Homocysteine
      thialactone (a by-product of homocysteine auto-oxidation) combines with native
      LDL to form oxidized LDL which is taken up by intimal macrophages to form foam
      cells which is the beginning of atheromatous plaques. Homocysteine has also
      influence on proliferation of vascular smooth muscle cells and collagen
      deposition in atheromatous plaque. In addition several retrospective and
      prospective studies have shown that hyperhomocysteinaemia is associated with
      atheromatous and vascular events. Observations in 80 clinical and epidemiological
      studies have indicated that hyper-homocysteinaemia is a risk factor for
      atherosclerotic disease. However there are some studies which conclude that
      homocysteine is not a major risk factor for coronary heart disease.

PMID- 12186152
TI  - Plasma homocysteine levels and cardiovascular risk in Indians.

PMID- 12186153
TI  - Homocysteine and hypertension.

PMID- 12186154
TI  - Role of nutritional supplementation in reducing the levels of homocysteine.
AB  - Elevated plasma homocysteine level is a risk factor for atherosclerotic disease.
      Plasma homocysteine levels are influenced by genetic, physiological and lifestyle
      factors. Among the lifestyle factors, diet plays a significant role. Dietary
      intakes of folate, vitamins B12, B6 and B2 have been reported to be inversely
      related to plasma homocysteine concentration. Prevalence of subclinical
      deficiencies of these vitamins is high in Indian population. Folate status is the
      major determinant of plasma homocysteine level and there is a strong inverse
      correlationship between plasma homocysteine level and serum or erythrocyte folate
      levels. A combination therapy with B vitamins--folate, vitamins B12 and B6 is an
      effective means to reduce elevated homocysteine levels in general people and in
      patients with myocardial infarction. To maintain low plasma homocysteine
      concentration, people should be advised to increase their consumption of pulses,
      eggs, green leafy vegetables and fruits which are rich in B vitamins.

PMID- 12186155
TI  - Treatment of hyperhomocysteinemia and its impact on disease.

PMID- 12186156
TI  - Hyperhomocysteinemia and vascular disease: role and implications.

PMID- 12186157
TI  - Methylenetetrahydrofolate reductase gene mutation and hyperhomocysteinemia as a
      risk factor for coronary heart disease in the Indian population.
AB  - OBJECTIVE: The screening and therapeutic guidelines for the management of lipid
      abnormalities are reasonably well established. However, other risk factors like
      hyperhomocysteinemia (HCA) and single nucleotide polymorphisms involving the
      angiotensin converting enzyme (ACE) and angiotensinogen genes, various clotting
      factors etc., have yet to be established firmly as other causative factors of
      atherothrombotic disease. Our study was aimed at finding the relationship between
      HCA, folate, vitamins B12 levels, and mutations in the 5,10
      methylenetetrahydrofolate reductase (MTHFR) and cystathionine beta-synthase (CBS)
      genes. METHODS: We studied 230 subjects, which included patients with
      angiographically documented coronary heart disease (CHD) (n=115) and controls
      (n=115) with no history of CHD. RESULTS: Elevated levels of plasma homocysteine,
      above 18 nmoles/ml, were detected in 19.13% and 18.26% of our patients and
      controls, respectively. Homocysteine was significantly correlated to Apo A1
      (r=0.51, p < 0.05) and Apo B (r=0.49, p < 0.05). The heterozygous MTHFR mutation
      was found to be 54.5% (12/22) in our patients with HCA. Of these, 31.8% (7/22)
      were deficient for plasma folate. Heterozygosity for T833C mutation in the CBS
      gene was observed in 9.99% (2/22) of our patients with HCA. Both these patients
      were also deficient for plasma folate and vitamin B12. CONCLUSION: In our study,
      heterozygosity for the thermolabile MTHFR mutation was found to be associated
      with hyperhomocysteinemia (HCA). This genetic predisposition to HCA could be risk
      factor for CHD and can be correlated with vitamin supplementation. To the best of
      our knowledge this is the first report from India on plasma homocysteine levels
      and its genetic aspect in patients with CHD.

PMID- 12186158
TI  - Promising deliveries, delivering promises.

PMID- 12186159
TI  - Effects of marijuana on young adults.

PMID- 12186160
TI  - Effects of marijuana on young adults.

PMID- 12186161
TI  - Effects of marijuana on young adults.

PMID- 12186162
TI  - Canadian medical students voice their concerns.

PMID- 12186163
TI  - Canadian medical students voice their concerns.

PMID- 12186164
TI  - Canadian medical students voice their concerns.

PMID- 12186165
TI  - Quelling research excellence in residency programs.

PMID- 12186166
TI  - Transparency at Health Canada.

PMID- 12186167
TI  - Incidence of neural tube defects in Ontario, 1986-1999.
AB  - BACKGROUND: Prenatal screening and the promotion of folic acid intake could
      affect the incidence of neural tube defects (NTDs). We examined trends in the
      total NTD incidence, as detected in live births, stillbirths and therapeutic
      abortions, from 1986 to 1999 in Ontario. METHODS: To capture cases of NTDs we
      used data from the Canadian Congenital Anomalies Surveillance System and hospital
      data on therapeutic abortions. We calculated the total incidence of NTDs by
      combining the numbers of NTDs occurring in live births, stillbirths and
      therapeutic abortions. RESULTS: The total NTD incidence rate increased from 11.7
      per 10,000 pregnancies in 1986 to 16.2 per 10,000 in 1995, and it subsequently
      decreased to 8.6 per 10,000 by 1999. The NTD birth rate (live births and
      stillbirths) decreased from 10.6 per 10,000 births in 1986 to 5.3 per 10,000 in
      1999. The rate of therapeutic abortions with an NTD or hydrocephalus rose from
      17.5 per 10,000 abortions in 1986 to 50.7 per 10,000 in 1995 and fell to 28.7 per
      10,000 abortions in 1999. INTERPRETATION: The total NTD incidence rate increased
      from 1986 to 1995, probably because of increased prenatal screening and better
      detection of NTDs. The decline from 1995 to 1999 may have been due to increased
      folic acid intake among women at the time of conception.

PMID- 12186168
TI  - Incidence of open neural tube defects in Nova Scotia after folic acid
      fortification.
AB  - BACKGROUND: With the goal of preventing open neural tube defects (NTDs),
      recommendations for folic acid supplementation before conception were introduced
      in Canada in 1994, and by November 1998 Canadian grain products were being
      fortified with folic acid. We wished to determine whether the annual incidence of
      open NTDs in Nova Scotia, including those in stillbirths and terminated
      pregnancies, changed after the introduction of either folic acid supplementation
      or fortification. METHODS: For the 10-year period from Jan. 1, 1991, to Dec. 31,
      2000, we retrospectively extracted the total number of births in Nova Scotia and
      the number of live births and stillbirths with open NTDs from the Nova Scotia
      Atlee Perinatal Database as well as the number of terminated pregnancies affected
      by NTDs from the Fetal Anomaly Database. We determined the total annual incidence
      of all open NTDs, and of the subgroups spina bifida and anencephaly, per 1000
      births in the province during the periods before (1991-1994) and after (1995
      1998) folic acid supplementation initiatives were begun but before folic acid
      fortification of grain products was implemented, and during the periods before
      (1991-1997) and after (1998-2000) fortification. RESULTS: In the period after
      supplementation initiatives were begun but before fortification was implemented,
      the incidence of open NTDs did not change significantly: the mean annual rate was
      2.55 per 1000 births during 1991-1994 and 2.61 per 1000 births during 1995-1997
      (relative risk [RR] 1.02, 95% confidence interval [CI] 0.77-1.35). After the
      fortification was implemented the incidence of open NTDs decreased by more than
      50%: the mean annual rate was 2.58 per 1000 births during 1991-1997 and 1.17 per
      1000 births during 1998-2000 (relative risk 0.46, 95% CI 0.32-0.66).
      INTERPRETATION: The recommendations for folic acid supplementation alone did not
      appear to succeed in reducing the incidence of open NTDs in Nova Scotia, whereas
      the fortification of grain products with folic acid did result in a significant
      reduction in the incidence.

PMID- 12186169
TI  - The effects of cost-sharing on essential drug prescriptions, utilization of
      medical care and outcomes after acute myocardial infarction in elderly patients.
AB  - BACKGROUND: After a change in Quebec's policy on drug coverage in August 1996,
      elderly patients' copayments for prescription drugs increased. We assessed the
      impact of this drug policy reform on prescribing patterns for essential cardiac
      medications, utilization of medical care and related health outcomes after acute
      myocardial infarction. METHODS: Patients at least 65 years of age who experienced
      acute myocardial infarction between 1994 and 1998 were identified through the
      Quebec discharge summary database. Drug claims databases were analyzed to
      determine rates of prescription of essential cardiac medications for cohorts of
      patients admitted before and after the policy reform. The impact on readmissions
      for cardiac-related complications, outpatient visits to physicians and emergency
      departments, and mortality rate was also assessed. RESULTS: The proportion of
      patients who received prescriptions for beta-blockers, angiotensin-converting
      enzyme inhibitors and lipid-lowering drugs increased over time and, more
      specifically, did not appear to decline with the change in the drug policy. In
      addition, the policy reform did not appear to affect persistence of drug therapy
      (the proportion of time for which patients were covered by prescriptions over the
      year after discharge). There was no within-class shift from more to less
      expensive drugs. Use of cardiac procedures increased over time, but this increase
      was unrelated to the date of the policy reform. Finally, rates of readmission for
      complications, visits to individual physicians and to emergency departments, and
      mortality rate were unchanged. The findings did not vary with sex or
      socioeconomic status. INTERPRETATION: Prescriptions for essential cardiac
      medications and care related to acute myocardial infarction in elderly patients
      did not change with increases in out-of-pocket copayment, regardless of sex or
      socioeconomic status.

PMID- 12186170
TI  - The very youngest science.

PMID- 12186171
TI  - Neural tube defects and periconceptional folic acid.

PMID- 12186172
TI  - Gene patents and the standard of care.

PMID- 12186173
TI  - Some thoughts on medicare.

PMID- 12186174
TI  - Patenting of genetic material: are the benefits to society being realized?

PMID- 12186175
TI  - Medical genetics: 1. Clinical teratology in the age of genomics.
AB  - Teratogenic exposures are those that can cause an embryo or fetus to develop
      abnormally. Several factors determine whether an agent is teratogenic, including
      the gestational timing of the exposure, as well as the dose, route and nature of
      the agent itself. We review the general concepts of teratogenesis, as well as
      known genetic susceptibilities to teratogenic effects, with a special focus on
      antiepileptic drugs. We discuss general principles of risk counselling and risk
      reduction, and we describe several long-known teratogens, as well as several
      exposures recognized only recently to have teratogenic potential.

PMID- 12186177
TI  - Grapefruit juice: potential drug interactions.

PMID- 12186176
TI  - Genetics 101: detecting mutations in human genes.

PMID- 12186178
TI  - Shigella: wash your hands of the whole dirty business.

PMID- 12186179
TI  - A child with axillary freckling and cafe au lait spots.

PMID- 12186180
TI  - Doctor shortage in Quebec a real numbers game.

PMID- 12186181
TI  - Ethicists race to keep pace with advances in biotechnology.

PMID- 12186182
TI  - DTC ads in US having huge impact on drug sales.

PMID- 12186183
TI  - Long waits in NHS casualty departments.

PMID- 12186184
TI  - Romanow vows to heed "health literate" Canadians.

PMID- 12186185
TI  - "Shared responsibility" becoming the new medical buzz phrase.

PMID- 12186186
TI  - Elimination of virus-specific cytotoxic T cells in the liver.
AB  - Immune responses in the liver have been studied for more than three decades,
      raising intriguing questions but providing few definitive answers. Many
      observations pertaining to immunity in this organ are unexpected and some of them
      even contradictory: parenchymal cells in the liver are readily accessible to
      circulating lymphocytes and may function as antigen-presenting cells (APC), yet
      antigens expressed in the liver often fail to induce responses and may cause
      systemic tolerance. There are rare lymphocyte classes in the liver, yet reasons
      why these cells reside in this organ and why immune responses are often poor
      remain to be elucidated. Here one of the central questions in immune responses in
      the liver is discussed (i.e., the ability of the adaptive T-cell-mediated immune
      response to clear a virus infection). An attempt is made to explain the
      intriguing observation that non-self-antigens expressed in the liver may induce
      unresponsiveness. It is shown that cell-mediated immunity to a viral infection is
      terminated, coincident with cell death of virus-specific cytotoxic T-lymphocytes
      (CTL) early after infection. Death of CTL is shown to involve interaction of Fas
      with Fas ligand, pointing to fratricide between activated CTL. The observation
      that T-cell death is inhibitable by injection of interleuken-2 is interpreted to
      point to a mechanism involving insufficient stimulation of T cells in conjunction
      with a death signal by Fas. The hypothesis is put forward that antigen
      presentation by unconventional APC in the liver leads to T-cell activation, in
      turn inducing lytic activity and expression of Fas and FasL on CTL. CTL then
      commit fratricide, aided by insufficient cytokine production and resulting in
      clonal elimination of virus-specific T cells and induction of tolerance.

PMID- 12186187
TI  - Immune privilege in the anterior chamber of the eye.
AB  - Since the 19th century, it has been recognized that the anterior chamber of the
      eye permits the prolonged, and sometimes permanent, survival of foreign tissue
      and tumor grafts. It was initially believed that the absence of patent lymphatics
      draining the interior of the eye prevented antigens from reaching regional
      lymphoid tissues. However, sequestration of intraocular antigens alone cannot
      account for ocular immune privilege, and a clear picture is now emerging that a
      constellation of anatomical, physiological, and dynamic immunoregulatory factors
      contribute to ocular immune privilege. Ocular fluids contain a potpourri of
      immunosuppressive and immunoregulatory factors that suppress T-cell proliferation
      and secretion of proinflammatory cytokines. The interior of the eye is decorated
      with Fas ligand (CD95L), which induces apoptosis of infiltrating inflammatory
      cells. Antigens introduced into the eye induce a unique immune deviation in which
      TH1 responses, namely delayed-type hypersensitivity (DTH), are actively
      suppressed. Thus, ocular immune privilege is sustained by factors that suppress
      immune cell proliferation and purge immune cells that enter the eye and by a
      dynamic immunoregulatory process that suppresses antigen-specific DTH.
      Suppression of certain inflammatory responses is an important adaptation for
      preventing immune-mediated injury to ocular tissues that have little or no
      capacity to regenerate. Thus, immune privilege is a crucial adaptation for
      preserving vision.

PMID- 12186188
TI  - The hepatic immune system.
AB  - The liver regulates T-cell homeostasis, induces T-cell tolerance, and supports
      intrahepatic T-cell responses against hepatotropic pathogens. Many data from
      clinical and preclinical systems provide supportive evidence for these diverse
      roles of the liver in modulating peripheral (systemic, mucosal, and intrahepatic)
      T-cell immunity. Little information is available on the cellular and molecular
      mechanisms that mediate the dual role of the liver in tolerizing T-cell responses
      and in supporting intrahepatic priming of T-cell responses. Understanding these
      immunoregulatory effects in the liver may offer insight into clinically relevant
      immunopathologies of this organ.

PMID- 12186189
TI  - Modelling the demographic impact of AIDS.

PMID- 12186190
TI  - AIDS in Papua New Guinea: situation in the Pacific.
AB  - There has long been reason to anticipate a major heterosexual epidemic of
      acquired immunodeficiency syndrome (AIDS) in Papua New Guinea (PNG) and probably
      in the rest of Melanesia. From the social and behavioural perspectives, Melanesia
      is strikingly similar to other areas of the world with serious epidemics of AIDS.
      High levels of other sexually transmitted infections indicate behaviour patterns
      that would also facilitate transmission of human immunodeficiency virus (HIV) and
      presence of cofactors for HIV infection. Low levels of male circumcision parallel
      the situation in other epidemic areas. Near-parity by sex in cases reported so
      far in PNG is evidence that primary infection is largely heterosexual. The late
      start of a major epidemic in PNG can probably be attributed to: (a) the
      relatively small aggregation of people in urban centres (even Port Moresby has
      only one-quarter of a million people); (b) a highway system that does not network
      across the whole country; (c) limited size of the organized commercial sex
      sector; and (d) possibly low level of chancroid to act as a cofactor. The
      situation is now changing. Over the last seven years, HIV infection, probably the
      highest in Port Moresby and mostly measured there, has been rising by about 60%
      per annum. This rise is genuine and, if sustained, would infect 10% of the adult
      population of PNG in little more than 12 years. Some countries of sub-Saharan
      Africa have witnessed such exponential rises.

PMID- 12186191
TI  - Effect of wealth on marital fertility in Sri Lanka.
AB  - This study examines the effect of household wealth on marital fertility in Sri
      Lanka. Data on type of dwelling, availability of vehicles, and electrical
      equipment in households were combined with estimates of 'typical' rupee values of
      various elements to generate an index of their wealth. Differentials in value of
      the wealth indices among sociodemographic subgroups of population are also
      described. The results of the study showed that, after controlling for other
      variables, higher levels of household wealth were associated with lower
      fertility. There were also significant effects of participation of female labour
      force, ethnicity, age-at-marriage, and parity on current fertility. However,
      after controlling for wealth and other explanatory variables, the effect of
      female education was not significant. If the model were to remain constant over
      time, raising levels of wealth would reduce marital fertility in Sri Lanka.

PMID- 12186192
TI  - Demographic impact of AIDS in a low-fertility urban African setting: projection
      for Addis Ababa, Ethiopia.
AB  - The study estimated the potential demographic impact of acquired immunodeficiency
      syndrome (AIDS) in a low-fertility urban setting in sub-Saharan Africa. The
      prevalence of human immunodeficiency virus (HIV) projected using a deterministic
      mathematical model was put into the AIDS Impact Model (AIM) of the SPECTRUM
      Policy Modelling System to estimate the potential demographic impact ofAIDS in
      Addis Ababa, Ethiopia. Demographic indicators from 1984 (the start of the HIV
      epidemic in Ethiopia) to 2024, including and excluding the HIV epidemic, were
      compared. Addis Ababa is experiencing a demographic transition in which the total
      fertility rate has declined from 3.8 to below replacement level over the last 20
      years. The prevalence of HIV is predicted to stabilize at 10% in adults,
      resulting in a total number of people living with HIV at 200,000 and a cumulative
      number of deaths due to AIDS at 50,000. About 60% of adult deaths can be
      attributable to AIDS by 2000. The epidemic is predicted to reduce life expectancy
      by 10 and 17 years in 2000 and 2024 respectively, and to turn to negative, the
      rate of natural increase after 2009. Accordingly, the rate of natural increase
      will be -0.18%, -0.35%, and -0.71% per annum by 2009, 2014, and 2024
      respectively. Population growth is expected to continue with or without HIV, as a
      result of high net in-migration, although data for migration are scanty. In a low
      fertility urban society of Africa, this study shows the potential for the
      HIV/AIDS epidemic to turn the rate of natural increase to negative.

PMID- 12186193
TI  - Knowledge on AIDS among female adolescents in Bangladesh: evidence from the
      Bangladesh demographic and health survey data.
AB  - To assess the knowledge on acquired immunodeficiency syndrome (AIDS) among female
      adolescents in Bangladesh, this study used data extracted from the Bangladesh
      Demographic and Health Survey (BDHS) 1996-1997. Of 1,446 ever-married women
      included in the study, most were currently married (96%), Muslims (92%) and from
      rural areas (91%). Only one in six adolescents had ever heard of AIDS. Of them,
      57% reported AIDS as a fatal disease almost always, while only 22% believed that
      AIDS could be avoided. Multivariate analysis revealed that knowledge on AIDS was
      strongly and positively associated with education of female adolescents and their
      husbands and varied significantly across different parts of the country.
      Knowledge on AIDS was higher among relatively older and urban residents who had
      access to television or radio and whose husbands were using condom. Strong
      efforts are needed to improve awareness and to clarify misconceptions about AIDS.
      Improved access to education, mass-media, and promotion of condom use could
      prevent AIDS among female adolescents in Bangladesh.

PMID- 12186194
TI  - Infant mortality in India: use of maternal and child health services in relation
      to literacy status.
AB  - Slow reduction in infant mortality rate in the last couple of decades is a major
      concern in India. State-level aggregate data from the National Family Health
      Survey 1992 and micro-level data on rural mothers (n=317) were used for examining
      the influence of female literacy on reduction of infant mortality through
      increased use of maternal and child health (MCH) services. Illiteracy of females
      was strongly associated with all variables relating to maternal care and also
      with infant mortality rate. States were grouped into best, medium, and worst on
      the basis of female illiteracy (about 11%, 48.5%, and 75% respectively). Infant
      mortality rate (per 1,000 livebirths) was significantly (p<0.01) higher among the
      worst group (90.99) than that among the medium (64.2) and the best (24.0) groups.
      Use of maternal health services increased in the worst to become the best groups
      for tetanus toxoid (from 48.0% to 84.4%), iron and folic acid tablets (36.6% to
      76.2%), hospitalized deliveries (14.2% to 69.7%), and childcare services, such as
      vaccination (23.8% to 64.9%). Illiteracy of females had a more detrimental impact
      on rural than on urban areas. In the event of high female illiteracy, male
      literacy was beneficial for improving the use of services for reducing infant
      mortality rate. The micro-level study supported all major findings obtained for
      the national-level aggregate data. Programmes, like providing free education to
      girls, will yield long-term health benefits.

PMID- 12186195
TI  - Pathways to infant mortality in urban slums of Delhi, India: implications for
      improving the quality of community- and hospital-based programmes.
AB  - The study aimed at obtaining insights into the processes underlying infant deaths
      to help identify preventive interventions which may bring down infant mortality
      rates further. Verbal autopsies were performed on 162 deaths of liveborn infants
      that occurred in a birth cohort in two urban slums of Delhi, India, between
      February 1995 and August 1996. A structured verbal autopsy form was used for
      ascertaining the cause of death. The narratives of caretakers on seeking of care
      and treatment received for illness were reviewed to identify the actions and
      behaviours that might have contributed to death. Seeking of care was less common
      (57%) for illnesses that led to death in the first week of life than at later
      ages. The first-week deaths commonly (61%) occurred within 24 hours of
      recognition of illness which might have been too a short time for effective
      interventions by care providers. Only six of 45 neonates who had features of
      sepsis, pneumonia or meningitis, major congenital malformations, birth asphyxia,
      or prematurity were advised by primary care providers for hospitalization.
      Similarly, only 25 (41%) of 61 older infants who had severe malnutrition and
      sepsis or meningitis, diarrhoea or pneumonia, or other illnesses were referred to
      hospital. Parenteral antibiotics were prescribed less often than warranted. Only
      two of 16 neonates with serious bacterial infections and eight of 19 postneonates
      with features of sepsis or meningitis received parenteral antibiotics.
      Inappropriate healthcare practices were common among the practitioners of modern
      and indigenous systems of medicine and registered medical practitioners. Forty
      percent of the neonates and a little over half of the older infants, advised for
      hospitalization, were taken to hospital. Fifteen percent of the infants taken to
      hospital were refused admission. Of 21 hospitalized infants discharged alive,
      five (23%) died within 48 hours and 13 (62%) within a week of returning home. A
      major effort is required to improve skills of healthcare providers of the
      biomedical and indigenous systems of medicine in caring for neonates and infants.
      Development of home-based treatment regimens for young infants and objective
      criteria for their hospitalization and discharge should receive a high priority.

PMID- 12186196
TI  - Increasing contraceptive acceptance through empowerment of female community
      health volunteers in rural Nepal.
AB  - The purpose of the study was to enhance contraceptive acceptance among currently
      married women of reproductive age (CMWRA) through empowerment training of female
      community health volunteers (FCHVs). Seventeen FCHVs, who were working in Kakani
      Village Development Committee in the hills of central Nepal, attended an
      empowerment training that used participatory action research and reinforcement
      mechanisms. Following the training, the FCHVs were expected to empower the CMWRA
      to increase their contraceptive use. The impact of the intervention was assessed
      in a sample of 241 CMWRA, who were neither pregnant nor using contraceptives at
      the time of selection, by interviewing them before and six months after the
      intervention. The implementation of the intervention significantly increased the
      proportion of CMWRA knowing at least one contraceptive method (chi2(ldr)=71 .7,
      p=0.001). The use of modern contraceptives among the CMWRA from none before the
      intervention increased to 52.3% six months following the intervention.
      Satisfaction of the CMWRA with services provided by the FCHVs also significantly
      increased. The study concludes that empowerment training of FCHVs using
      participatory action research and peer reinforcement help increase the acceptance
      of contraceptives among CMWRA.

PMID- 12186197
TI  - Serum lipid profiles and risk of cardiovascular disease in three different male
      populations in northern Nigeria.
AB  - The Fulani of northern Nigeria are indigenous semi-nomadic pastoralists whose
      diet consists largely of dairy products. Despite their consumption of relatively
      large amounts of saturated fats, an earlier study showed that their total
      cholesterol, high-density lipoprotein (HDL), low-density lipoprotein (LDL) and
      serum triglyceride levels fall within the reference range of values for North
      Americans. Men in the cities of Jos and Abuja, two populations who also reside in
      northern Nigeria, differ from the Fulani with regard to diet and activity level.
      Males in both Jos and Abuja have diets consisting of high protein or carbohydrate
      and are more sedentary than the Fulani subjects. The main aims of the study were
      to measure the concentrations of various lipids in the blood serum of male urban
      dwellers in Jos and Abuja and to compare their blood lipid profiles with those of
      the rural Fulani (mean age 33.9 years). Blood serum samples from 118 men in Jos
      (mean age 37.9 years) and 77 men in Abuja (mean age 34.4 years) were analyzed for
      total cholesterol, triglycerides, LDL, HDL, homocysteine, folate, and vitamin
      B12. In addition to height and weight, systolic and diastolic blood pressures
      were measured. The mean total cholesterol, triglyceride, HDL and LDL values for
      the three groups of subjects fell within or close to the accepted range of values
      for North Americans. However, the Fulani males had HDL values (mean, 33.9 mg/dL)
      below the range of values prescribed for North Americans (>40 mg/dL). Moreover,
      the Fulani men and the men in Abuja had a total cholesterol/ HDL ratio of 4.2 and
      4.0 respectively, which exceed the accepted value (< or =3.5) prescribed by the
      Columbia University. In all three populations, the incidence ofhomocysteinaemia
      (serum homocysteine > 12.4 micromol/L) was very high. Their mean homocysteine
      levels ranged from 14.7 to 16.7 pmol/L and could not be accounted for by folate
      or vitamin B12 status. The mean blood pressures of the Abuja (127/77 mm Hg) and
      the Fulani (120/74 mm Hg) men were within the normotensive range (<130/85 mm Hg).
      However, the mean blood pressures of the Jos males (131/85 mm Hg) indicated
      borderline hypertension. These data indicate that, with regard to serum lipids,
      urban and rural adult Nigerian males have generally favourable risk factors for
      cardiovascular disease when compared with healthy North Americans. All three sub
      populations, however, have levels of homocysteine that are cause for concern vis
      a-vis their overall health status.

PMID- 12186198
TI  - Do side-effects reduce compliance to iron supplementation? A study of daily- and
      weekly-dose regimens in pregnancy.
AB  - Side-effects of iron supplementation lead to poor compliance. A weekly-dose
      schedule of iron supplementation rather than a daily-dose regimen has been
      suggested to produce fewer side-effects, thereby achieving a higher compliance.
      This study compared side-effects of iron supplementation and their impact on
      compliance among pregnant women in Bangladesh. These women were assigned to
      receive either weekly doses of 2 x 60 mg iron (one tablet each Friday morning and
      evening) or a daily dose of 1 x 60 mg iron. Fifty antenatal care centres were
      randomly assigned to prescribe either a weekly- or a daily-supplementation
      regimen (86 women in each group). Side-effects were assessed by recall after one
      month of supplementation and used for predicting compliance in the second and
      third months of supplementation. Compliance was monitored using a pill bottle
      equipped with an electronic counting device that recorded date and time whenever
      the pill bottle was opened. Of five gastrointestinal side-effects (heartburn,
      nausea, vomiting, diarrhoea, or constipation) assessed, vomiting occurred more
      frequently in the weekly group (21%) than in the daily group (11%, p<0.05).
      Compliance (ratio between observed and recommended tablet intake) was
      significantly higher in the weekly-supplementation regimen (93%) than in the
      daily-supplementation regimen (61%, p<0.05). Overall, gastrointestinal side
      effects were not significantly associated with compliance. However, the presence
      of nausea and/or vomiting reduced compliance in both the regimens-but only among
      women from the lower socioeconomic group. In conclusion, weekly supplementation
      of iron in pregnancy had a higher compliance compared to daily supplementation of
      iron despite a higher frequency of side-effects. The findings support the view
      that gastrointestinal side-effects generally have a limited influence on
      compliance, at least in the dose ranges studied. Efforts to further reduce side
      effects of iron supplementation may not be a successful strategy for improving
      compliance and effectiveness of antenatal iron supplementation.

PMID- 12186200
TI  - Traditional practice of oil massage of neonates in Bangladesh.
AB  - Topical application of natural oils is practised routinely in many countries and
      may either improve skin barrier function and health or have detrimental cutaneous
      and systemic effects, depending on the composition of the oil. Little literature
      on the epidemiology, practice, and perceptions of traditional neonatal oil
      massage is available. This study was undertaken to gain insights into the
      epidemiology, practice, and perceptions regarding traditional oil massage of
      Bangladeshi neonates. A questionnaire was administered verbally to the primary
      caretaker of 332 outpatients at the Dhaka Shishu Hospital, and to 20 women with
      children encountered at the Matlab Health Complex in Bangladesh. More than 96%
      (340/352) of the caregivers practised oil massage, irrespective of socioeconomic
      status and place of residence. Among those at the Dhaka Shishu Hospital who
      practised oil massage, mustard oil was used alone or in combination by 95%
      (303/320) over the entire body, 1-3 time(s) daily (96%), starting in the first
      three days of life (72%) in both term and preterm neonates. Perceived benefits
      included prevention of infections (69%) and hypothermia (2%). Oil massage is an
      important traditional domiciliary practice used annually on more than three
      million newborns in Bangladesh. Given its potential for beneficial and harmful
      effects, further research is needed on the value of this practice, and ways to
      optimize its beneficial effects.

PMID- 12186201
TI  - Surveillance of enterohaemorrhagic Escherichia coli O157:H7 in southern Thailand.

PMID- 12186199
TI  - Iodine deficiency disorders among school children of Malda, West Bengal, India.
AB  - A community-based, cross-sectional study was conducted among 2,392 school
      children, aged 8-10 years, in Malda district of West Bengal, India, in January
      2001 to assess their iodine status. The children were selected through a
      multistage 30 cluster-sampling technique to determine the status of iodine
      deficiency disorders (IDD) using recommended quantifiable indicators. The
      prevalence of goitre was assessed clinically using the standard palpation method
      by the teachers of Community Medicine, and a total goitre rate of 11.3% was found
      with no significant gender difference (p>0.05). Urinary iodine excretion (UIE)
      levels of 341 study subjects, selected through systematic random sampling, were
      analyzed by the wet digestion method to determine biochemical iodine deficiency
      by the teachers of Biochemistry Department. The median UIE was 15 mcg/dL, and no
      child had UIE value less than 5 mcg/dL. Iodine content of 1,060 salt samples
      tested with spot-testing kit revealed 85.1% with adequate iodine content of > or
      = 15 ppm. The finding of 11.3% of total goitre rate but with no evidence of
      current iodine deficiency (median UIE 15 mcg/dL) indicates that the Malda
      district is in the transition phase from iodine-deficient to iodine-sufficient.

PMID- 12186202
TI  - Fertility and wealth in Sri Lanka: are children normal goods?

PMID- 12186203
TI  - Trends in antimicrobial susceptibility patterns among inpatient enterococcal
      isolates (1990 to 1999): implications for therapeutic options.

PMID- 12186204
TI  - Improving healthcare workers' compliance with hand hygiene: is a picture worth a
      thousand words?

PMID- 12186205
TI  - Control of vancomycin-resistant enterococci: it is important, it is possible, and
      it is cost-effective.

PMID- 12186206
TI  - A prospective study to determine whether cover gowns in addition to gloves
      decrease nosocomial transmission of vancomycin-resistant enterococci in an
      intensive care unit.
AB  - BACKGROUND: Vancomycin-resistant enterococci (VRE) remain a significant
      nosocomial pathogen. Current guidelines of the Hospital Infection Control
      Practices Advisory Committee (HICPAC) of the Centers for Disease Control and
      Prevention (CDC) recommend the use of gowns and gloves for some interactions with
      VRE-infected or -colonized patients to prevent nosocomial transmission of VRE.
      OBJECTIVE: To assess the effect of disposable cover gowns on preventing
      nosocomial transmission of VRE. DESIGN AND SETTING: Prospective study in a 16-bed
      medical intensive care unit of a university teaching hospital. PATIENTS: All
      patients who were at risk to acquire VRE, were admitted to the intensive care
      unit from August 1998 to January 1999, and had at least two perirectal cultures
      were included in the analysis of VRE acquisition. INTERVENTION: VRE isolation
      precautions were changed from gowns and gloves to gloves alone. MAIN OUTCOME risk
      factors for VRE acquisition. RESULTS: The VRE acquisition rate was 1.80 cases per
      100 days at risk in the gown and gloves period compared with 3.78 in the gloves
      only period (P = .04). In a proportional hazards model adjusted for length of
      stay, gloves only precautions with a hazard ratio of 2.5 (P = .02; 95% confidence
      interval, 1.2 to 5.3) were the only independent risk factor for VRE acquisition.
      CONCLUSION: Our data lend support to current HICPAC recommendations for the use
      of cover gowns to decrease nosocomial transmission of VRE.

PMID- 12186207
TI  - Cost-effectiveness of perirectal surveillance cultures for controlling vancomycin
      resistant Enterococcus.
AB  - BACKGROUND: Several hospitals opting not to use active surveillance cultures to
      identify carriers of vancomycin-resistant Enterococcus (VRE) have reported that
      adoption of other parts of the Centers for Disease Control and Prevention
      guideline for controlling VRE has had little to no impact. Because use of
      surveillance cultures and contact isolation controlled a large outbreak at this
      hospital, their costs were estimated for comparison with the excess costs of VRE
      bacteremias occurring at a higher rate at a hospital not employing these
      measures. SETTING: Two university hospitals. METHODS: Inpatients deemed high risk
      for VRE acquisition at this hospital underwent weekly perirectal surveillance
      cultures. Estimated costs of cultures and resulting isolation during a 2-year
      period were compared with the estimated excess costs of more frequent VRE
      bacteremias at another hospital of similar size and complexity not using
      surveillance cultures to control spread throughout the hospital. RESULTS: Of
      54,052 patients admitted, 10,400 had perirectal swabs taken. Cultures and
      isolation cost an estimated $253,099. VRE culture positivity was limited to 193
      (0.38%) and VRE bacteremia to 1 (0.002%) as compared with 29 bacteremias at the
      comparison hospital. The estimated attributable cost of VRE bacteremia at the
      comparison hospital of $761,320 exceeded the cost of the control program at this
      hospital by threefold. CONCLUSIONS: The excess costs of VRE bacteremia may
      justify the costs of preventive measures. The costs of VRE infections at other
      body sites, of deaths from untreatable infections, and of dissemination of genes
      for vancomycin resistance also help to justify the costs of implementing an
      effective control program.

PMID- 12186208
TI  - Recurrence of vancomycin-resistant Enterococcus stool colonization during
      antibiotic therapy.
AB  - OBJECTIVE: To test the hypothesis that antibiotic therapy may promote recurrence
      of vancomycin-resistant Enterococcus (VRE) stool colonization in patients who
      have previously had three consecutive negative stool cultures obtained at least 1
      week apart. DESIGN: One-year prospective cohort study examining the effect of
      antibiotic therapy on recurrence and density of VRE stool colonization in
      patients who have cleared colonization. Pulsed-field gel electrophoresis (PFGE)
      was performed to determine whether recurrent VRE strains were the same clone as
      the previous colonizing strain. SETTING: A Department of Veterans Affairs medical
      center including an acute care hospital and nursing home. PATIENTS: All patients
      with at least one stool culture positive for VRE who subsequently had three
      consecutive negative stool cultures obtained at least 1 week apart. RESULTS: Of
      the 16 patients who cleared VRE colonization, 13 received antibiotic therapy
      during the study period. Eight (62%) of the 13 patients who received antibiotics
      developed recurrent high-density VRE stool colonization (range, 4.9 to 9.1 log10
      colony-forming units per gram) during a course of therapy. Five patients had VRE
      strains available for PFGE analysis; recurrent strains were unrelated to the
      prior strain in 3 patients, closely related in 1 patient, and indistinguishable
      in 1 patient. CONCLUSIONS: Antibiotic therapy may be associated with recurrent
      high-density VRE stool colonization in many patients who have previously had
      three consecutive negative stool cultures. These patients should be screened for
      recurrent stool colonization when antibiotic therapy is administered.

PMID- 12186209
TI  - An outbreak of multidrug-resistant Pseudomonas aeruginosa associated with
      increased risk of patient death in an intensive care unit.
AB  - OBJECTIVE: To investigate an outbreak of multidrug-resistant Pseudomonas
      aeruginosa in an intensive care unit (ICU). DESIGN: Epidemiologic investigation,
      environmental assessment, and ambidirectional cohort study. SETTING: A secondary
      care university hospital with a 10-bed ICU. PATIENTS: All patients admitted to
      the ICU receiving ventilator treatment from December 1, 1999, to September 1,
      2000. RESULTS: An outbreak in an ICU with multidrug-resistant isolates of P
      aeruginosa belonging to one amplified fragment-length polymorphism (AFLP)-defined
      genetic cluster was identified, characterized, and cleared. Molecular typing of
      bacterial isolates with AFLP made it possible to identify the outbreak and make
      rational decisions during the outbreak period. The outbreak included 19 patients
      during the study period. Infection with bacterial isolates belonging to the AFLP
      cluster was associated with reduced survival (odds ratio, 5.26; 95% confidence
      interval, 1.14 to 24.26). Enhanced barrier and hygiene precautions, cohorting of
      patients, and altered antibiotic policy were not sufficient to eliminate the
      outbreak. At the end of the study period (in July), there was a change in the
      outbreak pattern from long (December to June) to short (July) incubation times
      before colonization and from primarily tracheal colonization (December to June)
      to primarily gastric or enteral July) colonization. In this period, the bacterium
      was also isolated from water taps. CONCLUSION: Complete elimination of the
      outbreak was achieved after weekly pasteurization of the water taps of the ICU
      and use of sterile water as a solvent in the gastric tubes.

PMID- 12186210
TI  - Molecular characterization of methicillin-resistant coagulase-negative
      staphylococci from a neonatal intensive care unit.
AB  - OBJECTIVE: To evaluate clonal dissemination of methicillin-resistant coagulase
      negative staphylococci (CNS). SETTING: Neonatal intensive care unit of a 180-bed,
      university-affiliated general hospital. PATIENTS: Neonates admitted to the
      neonatal intensive care unit between March 1999 and October 2000, from whom CNS
      were isolated as a unique pathogen. Patients from other wards from whom
      epidemiologically unrelated staphylococci strains were obtained served as control
      patients. METHODS: Conventional methods were used for phenotypic characterization
      of CNS. Methicillin resistance was determined by mecA polymerase chain reaction
      (PCR) amplification. Genotypic characterization was done by random amplification
      of DNA with degenerated primers (RAPD) and repetitive element sequence-based PCR
      (rep-PCR). RESULTS: Forty methicillin-resistant CNS isolates obtained from
      neonates were characterized as Staphylococcus epidermidis (33), S. hominis (5),
      S. warneri (1), and S. auricularis (1). Both RAPD and rep-PCR indicated the
      presence of 4 different clones among the 33 S. epidermidis isolates. In turn, the
      4 randomly selected, epidemiologically unrelated methicillin-resistant CNS
      strains obtained from control-patients showed 3 new profiles by RAPD and 2 by rep
      PCR, which differed from the corresponding patterns mentioned earlier.
      Persistence of S. hominis in a neonate could be assessed by both genotypic
      techniques. CONCLUSIONS: The molecular characterization of the methicillin
      resistant CNS studied indicated dissemination of one particular methicillin
      resistant CNS clone among the neonates in the ward studied. Although RAPD showed
      a superior power to discriminate among methicillin-resistant CNS isolates, both
      RAPD and rep-PCR detected intraspecific and interspecific genomic diversity.

PMID- 12186211
TI  - Risk factors for infection and molecular typing in patients in the intensive care
      unit colonized with nosocomial Enterobacter aerogenes.
AB  - OBJECTIVES: To determine the frequency of colonization by Enterobacter aerogenes
      in patients in the intensive care unit (ICU) for more than 48 hours and to
      evaluate the risk factors for infection in patients colonized by this bacteria.
      DESIGN: An 8-month prospective study. SETTING: A 12-bed medical-surgical ICU in a
      450-bed, university-affiliated, tertiary-care hospital in Belgium. METHOD: Pulsed
      field gel electrophoresis was used to determine the genotypes of E. aerogenes
      isolates. RESULTS: We observed two major clones of E. aerogenes in the ICU.
      Interestingly, 87.5% of infected patients had the same genomic profile for
      colonization and infection. Risk factors for infection in this particular
      population included younger age, prolonged hospital stay, mechanical ventilation,
      and bronchoscopy. CONCLUSIONS: Colonization is a major prerequisite for
      infection. The identification of risk factors for infection in colonized patients
      can optimize the quality of treatment in the ICU.

PMID- 12186212
TI  - Nosocomial outbreak of Serratia marcescens in a neonatal intensive care unit.
AB  - OBJECTIVES: To investigate and describe an outbreak of Serratia marcescens in a
      neonatal intensive care unit (NICU) and to report the interventions leading to
      cessation of the outbreak. SETTING: A 2,168-bed, tertiary-care, university
      teaching hospital in Vienna, Austria, with an 8-bed NICU. DESIGN: We conducted a
      case-control study to identify risk factors for colonization and infection with
      S. marcescens. A case-patient was defined as any neonate in the NICU with a
      positive culture for S. marcescens between October 1, 2000, and February 28,
      2001. Polymerase chain reaction was applied to type isolates. METHODS: During
      unannounced observations, the NICU was examined and existing policies were
      reviewed. Staff were reinstructed in hand antisepsis and gloving policies.
      Admissions were halted on December 27. During previously planned technical
      maintenance of the ward, the NICU was closed for 10 days and thorough aldehyde
      based disinfection of the NICU was performed. RESULTS: Ten neonates met the case
      definition: 6 with infections (among them 3 with cerebral abscesses) and 4 with
      asymptomatic colonization. Previous antibiotic treatment of the mothers with
      cefuroxime was the single significant risk factor for colonization or infection
      (P = .028; odds ratio, 17; 95% confidence interval, 1.3 to 489.5). CONCLUSIONS:
      S. marcescens can cause rapidly spreading outbreaks associated with fatal
      infections in NICUs. With aggressive infection control measures, such outbreaks
      can be stopped at an early stage. Affected neonates themselves may well be the
      source of cross-infection to other patients on the ward. Antibiotic treatment of
      mothers should be reevaluated to avoid unnecessary exposure to antibiotics with
      the potential of over-growth of resistant organisms.

PMID- 12186213
TI  - Patients in the intensive care unit are exposed to amoeba-associated pathogens.
AB  - OBJECTIVE: To study the role of amoeba-associated alpha Proteobacteria as
      infecting agents in intensive care units (ICUs). DESIGN: Amoeba-associated alpha
      Proteobacteria were isolated from water samples taken from ICU taps and general
      hospital reservoir tanks using an amoebal co-culture procedure. Isolates were
      identified by 16S rDNA gene sequence comparison, and one isolate of each species
      was used as an antigen in a microimmunofluorescence assay to test the sera of the
      patients in the ICUs and compare them with those of control subjects. SETTING:
      The four university hospitals in Marseilles, France. PATIENTS: The sera of 85
      patients in the ICUs with nosocomial pneumonia were tested. RESULTS: We isolated
      64 bacterial strains that were identified as Afipia species or close relatives
      within the Rhizobiaceae subgroup of alpha Proteobacteria. These bacteria were
      assigned to 8 different species. Eleven patients were found to have an elevated
      antibody titer to either Afipia genospecies 1, or 3 still unnamed bacteria. No
      specific antibodies were detected in 100 control subjects (P < .01). CONCLUSION:
      These preliminary results support the hypothesis that ICU patients are exposed to
      amoeba-associated alpha Proteobacteria.

PMID- 12186214
TI  - Prevalence and acquisition of vancomycin-resistant enterococci in a medical
      intensive care unit.
AB  - Patients admitted to a medical intensive care unit during 21 days had rectal and
      urine samples cultured for vancomycin-resistant enterococci (VRE). The prevalence
      rate was 55.3%. Only enteral feedings were associated with acquisition of VRE.
      One-quarter of VRE transmission resulted from acquisition in the study unit, 35%
      arrived from other units, and 15% from other hospitals.

PMID- 12186215
TI  - An outbreak of vancomycin-resistant enterococci in a hematology-oncology unit:
      control by patient cohorting and terminal cleaning of the environment.
AB  - We describe the impact of enhanced infection control interventions on controlling
      the spread of vancomycin-resistant enterococci (VRE) in our hematology-oncology
      unit. Between April and September 1998, 13 patients on this unit were identified
      as having VRE. In addition to contact precautions, other measures that were
      needed to control the outbreak included closure of the unit to new admissions,
      creation of a cohort of VRE-positive patients and staff, and thorough cleaning of
      patients' rooms with 0.5% sodium hypochlorite.

PMID- 12186216
TI  - Impact of infection by vancomycin-resistant Enterococcus on survival and resource
      utilization for patients with leukemia.
AB  - We estimated the impact of vancomycin-resistant Enterococcus (VRE) infection on
      the outcomes of patients with leukemia in a case-control study. Compared with
      their matched controls (n = 45), cases (n = 23) had 22% greater total charges and
      shorter survival (P = .04). These findings substantiate the need for aggressive
      interventions to prevent VRE transmission.

PMID- 12186218
TI  - Completely resistant Acinetobacter baumannii strains.
AB  - Nosocomially acquired completely resistant Acinetobacter baumannii strains are a
      major clinical concern. We identified completely resistant A. baumannii in 6
      (4.9%) of 122 A. baumannii isolates in a retrospective chart review at two
      teaching hospitals. All of these patients had received broad-spectrum antibiotics
      and had severe underlying comorbid illnesses, long hospitalizations, or recent
      surgical procedures; 3 had been in the intensive care unit. Five (83%) of the 6
      patients were older than 70 years. Only one death occurred. Strict infection
      control measures may limit further spread.

PMID- 12186217
TI  - Undetected vancomycin-resistant Enterococcus stool colonization in a Veterans
      Affairs Hospital using a Clostridium difficile-focused surveillance strategy.
AB  - We examined the point prevalence of undetected vancomycin-resistant Enterococcus
      (VRE) stool colonization in an institution that screens stool samples submitted
      for Clostridium difficile testing. Of 112 patients not known to be colonized, 10
      (9%) had rectal VRE colonization. A prospective algorithm was effective for
      identification of colonized patients.

PMID- 12186219
TI  - First case of VRSA identified in Michigan.

PMID- 12186220
TI  - Multistate outbreak of Escherichia coli O157:H7 infections associated with eating
      ground beef--United States, June-July 2002.
AB  - During July 2002, the Colorado Department of Public Health and Environment
      (CDPHE) identified an outbreak of Escherichia coli O157:H7 infections among
      Colorado residents. This report summarizes the results of an ongoing
      epidemiologic and laboratory investigation that has linked 28 illnesses in
      Colorado and six other states to eating contaminated ground beef products
      recalled by ConAgra Beef Company on June 30, 2002. To date, seven patients have
      been hospitalized; five developed hemolytic-uremic syndrome (HUS).

PMID- 12186222
TI  - Cigarette smoking among adults--United States, 2000.
AB  - One of the national health objectives for 2010 is to reduce the prevalence of
      cigarette smoking among adults to < or = 12% (objective 27.1a). To assess
      progress toward this objective, CDC analyzed self-reported data from the 2000
      National Health Interview Survey (NHIS) sample Adult Core questionnaire and
      Cancer Control module. This report summarizes the findings of this analysis,
      which indicate that, in 2000, approximately 23.3% of adults were current smokers
      compared with 25.0% in 1993, reflecting a modest but statistically significant
      decrease in prevalence among U.S. adults. In 2000, an estimated 70% of smokers
      said they wanted to quit, and 41% had tried to quit during the preceding year;
      however, marked differences in successful quitting were observed among
      demographic groups. A comprehensive approach to cessation that comprises
      economic, clinical, regulatory, and educational strategies is required to further
      reduce the prevalence of smoking in the United States.

PMID- 12186221
TI  - Methemoglobinemia following unintentional ingestion of sodium nitrite--New York,
      2002.
AB  - Methemoglobinemia is an unusual and potentially fatal condition in which
      hemoglobin is oxidized to methemoglobin and loses its ability to bind and
      transport oxygen. The most common cause of methemoglobinemia is the ingestion or
      inhalation of oxidizing agents such as nitrates or nitrites (e.g., sodium
      nitrite, which is used commonly as a preservative in curing meats and fish). This
      report summarizes the investigation of an incident of methemoglobinemia in five
      members of a household in New York who became ill after eating a meal seasoned
      with a white crystalline substance from a plastic bag labeled "Refined Iodized
      Table Salt" (Figure). The findings underscore the need for proper storage of
      hazardous materials to avoid unintentional ingestion and the importance of
      collaboration by multiple agencies to address a potential public health
      emergency.

PMID- 12186223
TI  - Weekly update: West Nile virus activity--United States, July 17-23, 2002.
AB  - This report summarizes West Nile virus (WNV) surveillance data reported to CDC
      through ArboNET and verified by states and other jurisdictions as of July 23,
      2002. During the reporting week of July 17-23, nine human cases of WNV were
      reported from two states (Louisiana and Mississippi). During the same period, WNV
      infections were reported in 202 dead crows, 48 other dead birds, 13 horses, and
      69 mosquito pools.

PMID- 12186224
TI  - National laboratory inventory as part of global poliovirus containment--United
      States, June 2002.
AB  - Since the initiation of the global poliomyelitis initiative in 1988 through 2001,
      the number of countries where polio is endemic decreased from 125 to 10, and the
      number of reported polio cases decreased >99%, from an estimated 350,000 to
      <1,000. The Global Commission for the Certification of the Eradication of
      Poliomyelitis, convened by the World Health Organization, will declare the world
      polio-free when all regions have documented the absence of wild poliovirus
      transmission for at least 3 consecutive years and when laboratories with wild
      poliovirus materials have implemented appropriate containment conditions.

PMID- 12186225
TI  - Relationship of perceived and actual motor competence in children.
AB  - The purpose of this study was to examine the relationship between children's
      actual and perceived motor competence. 280 children between the ages of 10 and 13
      years individually completed the Children's Physical Self-perception Profile
      which assesses perceptions of sport competence, physical conditioning, strength,
      body attractiveness, and general physical self-worth. The internal reliabilities
      (a) of the subscales ranged from .75 to .82. After completing the profile, the
      subject's actual motor competence was measured using tests of aerobic fitness and
      functional strength. Body fatness (sum of five skinfolds) was measured as an
      objective measure of perceived body attractiveness. Analysis of variance showed
      that boys and girls differed in perceived competence and actual motor competence.
      The boys showed higher perceived competence on four scores, but there was no sex
      difference in perception of body attractiveness. Correlations and regression
      analysis showed that actual and perceived motor competence were significantly but
      only moderately (r =.25-.56) correlated. In addition, items of perceived physical
      competence and age accounted for 17% (sit-ups) to 25% (endurance shuttle run) of
      the variance in actual motor competence of the children. These findings showed
      that 10- to 13-yr-old children can only moderately assess personal motor
      competence.

PMID- 12186226
TI  - Evidence for lack of change in seasonality of suicide from Timis County, Romania.
AB  - Evidence from politically and socially stable countries in Northern Europe and
      the Southern Hemisphere indicates a marked decrease in the seasonality of suicide
      over the past two decades. Generalizabiity of this trend to societies in
      transition has not yet been investigated. Data for suicide by hanging in Timis
      County of Romania show both a nondecrease in seasonality of suicide for the
      current transitional period (1990-98), relative to the last decade of the
      Communist regime (1980-89) and shifts in location for suicide peak and trough
      months. Recent decreases in the seasonality of suicide might not generalize to
      societies in transition, and research would improve from focusing on the "natural
      laboratories" these societies represent.

PMID- 12186227
TI  - A study into regional, age, and sex differences in students' ratings of cartoon
      humor.
AB  - Funniness ratings of cartoon humour by 366 university students showed no
      differences for age, sex, and region of origin, except for higher scores by men
      on work-related items. Ratings appear to be largely uninfluenced by factors other
      than how inherently amusing the items seem to be.

PMID- 12186228
TI  - Effects of speakers' augmented characteristics and listeners' sex on
      intelligibility and acceptability of synthesized speech.
AB  - 16 women and 16 men as listeners provided magnitude estimation scaling responses
      for the intelligibility and acceptability of synthesized speech transmitted by
      two different individuals using a voice output communication aid (VOCA).
      Listeners rated the samples when presented by a physically disabled nonspeaking
      male and when presented by a nondisabled speaking male. Analysis indicated no
      significant difference in listeners' judgments of the intelligibility or
      acceptability of the samples transmitted by the two VOCA users, regardless of sex
      of the listener or speaking ability of the presenter.

PMID- 12186229
TI  - A summary of U.S. skydiving fatalities: 1993-1999.
AB  - Between 1993 and 1999, 241 people died while participating in civilian
      recreational skydives in the United States. A taxonomy of skydiving fatalities
      was developed and used to categorize the fatalities.

PMID- 12186230
TI  - Exercise, fitness, and subjective measures related to fitness of physical
      education and other teachers.
AB  - The purpose of the present study was to examine the differences between physical
      and nonphysical education teachers in exercise, perceived and actual fitness,
      self-rated health, and attitudes toward aging. Participants were 307 women, 144
      physical education and 163 other teachers, mean age of 40.6 yr. (SD = 7.6).
      Factor analysis was performed to assess components of attitudes toward aging.
      Separate t tests on all variables were used to examine group differences,
      followed by discriminant analysis as a general model. Analysis indicated that
      physical education teachers were more active and fit, perceived their fitness as
      higher and rated their health and the physical component of attitudes toward
      their aging as more positive than those of nonphysical education teachers.
      Further exploration was recommended for the influence of early experiences with
      physical activity on later participation and the relations of physical activity,
      fitness, and subjective measures of well-being.

PMID- 12186231
TI  - Influence of sleep deprivation and auditory intensity on reaction time and
      response force.
AB  - Arousal and activation are two variables supposed to underlie change in response
      force. This study was undertaken to explain these roles, specifically, for strong
      auditory stimuli and sleep deficit. Loud auditory stimuli can evoke phasic
      overarousal whereas sleep deficit leads to general underarousal. Moreover, Van
      der Molen and Keuss (1979, 1981) showed that paradoxically long reaction times
      occurred with extremely strong auditory stimuli when the task was difficult,
      e.g., choice reaction or Simon paradigm. It was argued that this paradoxical
      behavior related to reaction time is due to active disconnecting of the coupling
      between arousal and activation to prevent false responses. If so, we predicted
      that for extremely loud stimuli and for difficult tasks, the lengthening of
      reaction time should be associated with reduction of response force. The effects
      of loudness and sleep deficit on response time and force were investigated in
      three different tasks: simple response, choice response, and Simon paradigm.
      According to our expectation, we found a detrimental effect of sleep deficit on
      reaction time and on response force. In contrast to Van der Molen and Keuss, we
      found no increase in reaction time for loud stimuli (up to 110 dB) even on the
      Simon task.

PMID- 12186232
TI  - Comparison of constant and variable practice conditions on free-throw shooting.
AB  - The proposition that variable practice may be superior to constant practice even
      for consistent transfer situations was tested on a prototypical consistently
      performed skill, the basketball free throw. 94 participants were matched on free
      throw shooting, then randomly assigned to one of four practice conditions, a
      Constant condition, i.e., at the free-throw line, and three Variable conditions.
      Under supervision participants practiced shooting free throws four days a week
      for three weeks. Three substantially different variable practice conditions
      produced significant improvement similar to that of constant practice on tests
      during each week of practice and on a delayed retention test. Consistent with the
      proposition, the most variable practice group performed as well as the other
      groups on the retention test despite lower practice performance.

PMID- 12186233
TI  - Do professional golfers "choke"?
AB  - A study involving results of the PGA Tour, Senior PGA Tour, and the LPGA Tour
      investigated whether "choking under pressure" occurs among professional golfers.
      Players were individuals who either were leading going into the final round or
      within five strokes of the lead. It was hypothesized that players who were one
      stroke from the lead and to a lesser extent players who were leading should have
      higher final round scores than those players who were two or more strokes from
      the lead ("choking"). However, the results did not support the choking
      hypothesis. Players who were leading going into the final round won the majority
      of the time.

PMID- 12186234
TI  - Modeling in learning two volleyball skills.
AB  - The present study was designed to investigate the influence of two different
      types of modeling and knowledge of performance on acquisition and retention of
      two volleyball skills (set and serve). Participants were 63 boys and 53 girls in
      elementary school, whose mean age was 11.7 yr. (SD=.5). The children were
      randomly assigned into two groups given the same practice method for 16 practice
      sessions (8 for the set and 8 for the serve) but different types of modeling.
      Some participants observed a videotape of an expert model performing the skills,
      and the second group observed a videotaped replay of their own performance.
      Verbal cues were provided simultaneously with the videotaped demonstration. The
      first group improved set and serve skills more on acquisition and on the
      retention test than the second group. This improvement was present when scores
      and form were evaluated. Modeling plus instructional cues seemed to improve
      children's learning of two volleyball skills (set and serve), and this procedure
      is suggested for use by practitioners.

PMID- 12186235
TI  - Intratest and intertest means and reliability of the MMPI-168 for university
      students and patients referred for neuropsychological assessment.
AB  - 68 first-year university students and 37 patients, after a 1-mo. or a 2-yr.
      interval, respectively, were re-administered the MMPI-168 (the first 168 items of
      the Minnesota Multiphasic Personality Inventory). The mean of the test-retest
      correlation coefficients between the first and second administrations for the 13
      scales (3 validity, 10 clinical) was about .62 for the students and the patients.
      The mean absolute change in standardized scores for the scales between the two
      administrations for both groups was only 0.2 of a standard deviation. Compared to
      the students, however, the patients who had been referred for neuropsychological
      assessments displayed elevated (>2 SD) mean scores for several of the scales
      during both administrations. These results indicate that the MMPI-168 profiles of
      the patients did not change appreciably even though several years had elapsed
      since the injuries. The correlation coefficients between means of the scaled
      scores between the first and second administrations for the students and patients
      were .91 and .95, respectively.

PMID- 12186236
TI  - Application of hidden Markov models on residuals: an example using Canadian
      traffic accident data.
AB  - Laverty, Kelly, Rotton, and Flynn conducted a regression analysis in 1992 on 9
      years of automobile accidents in Saskatchewan (a total of 200,545 accidents) to
      find a small linear trend, season effects, holiday, and day of the week effects.
      The application of a hidden Markov model to the residuals of this analysis
      uncovered two states which are likely to be related to the weather. These states
      can be described as low volatility' and 'high volatility'. The 'low volatility'
      state involves low variability compared to the 'high volatility' state (occurring
      during the colder months) during which the largest numbers of accidents occur. It
      is suggested that hidden Markov models are a useful method for uncovering hidden,
      underlying states in social science and health-related data.

PMID- 12186238
TI  - Two-component processes in switching attention: a study of event-related
      potentials.
AB  - When participants are asked either to repeat the task from the previous trial or
      switch to the other task, their reaction times are larger for switched than
      repeated tasks. This "switch cost" has been repeatedly demonstrated in behavioral
      studies. In this study, event-related potentials (ERPs) were recorded from 12
      healthy college students to assess whether this switch cost reflects component
      processes of preparation and interference. Analyses of ERPs showed that following
      the cue, there was greater positivity for a switched relative to a repeated trial
      when the tasks occurred in a fixed-order rather than in a random-order condition.
      Following the onset of the stimulus-pair, there was greater negativity for
      switched relative to repeated trials when the task stimulus consisted of both
      letters and digits but not when it consisted of either a letter or a digit paired
      with a neutral character. The data provide neurophysiological evidence for the
      two component processes.

PMID- 12186237
TI  - Effect of task difficulty on muscle activation patterns during rapid single-joint
      movements.
AB  - This study investigated the effect of spatial accuracy demands on movement
      organization by analyzing the amplitude of the agonist and antagonist muscle
      activities emerging during horizontal elbow-flexion movements toward spatial
      targets of varying difficulties. 8 subjects performed elbow-flexion movements
      toward targets of 3 sizes, located at 2 distances, as rapidly and accurately as
      possible. For each movement, the elbow angles and the activities of biceps
      brachii, brachioradialis, and lateral and long heads of triceps brachii were
      measured. Analysis on the kinematic variables indicated that final elbow angle
      and peak velocity decreased with increasing index of difficulty of the task in
      both movement-amplitude conditions. However, movement time increased with
      increasing index of difficulty. The amplitude of agonist and antagonist muscle
      activities measured for 100 msec. before movement initiation was also shown to
      decrease with increasing index of difficulty. Agonist and antagonist muscle
      activities measured during acceleration phase displayed similar patterns with
      those of premovement. These results suggest that the task difficulty affects
      movement organization, and the control system decreases the amplitude of agonist
      and antagonist muscle activities with an increase in the index of difficulty to
      enhance the controllability of the limb.

PMID- 12186239
TI  - Effects of fixed ratio schedules of reinforcement on exercise by college
      students.
AB  - Response-contingent reinforcement was expected to increase the time spent riding
      a stationary exercise cycle by college women. A single-subject experimental
      design was used. Three college-age women rode a stationary cycle until they were
      either too tired to continue or until 45 minutes elapsed. Video clips were used
      to reinforce cycling in the first part of the experiment. Under some conditions,
      no video clips were presented (baseline). In other conditions, the video was on
      for the entire session or 25 sec. of video was presented after the completion of
      FR 40 (40 rotations of the cycle's pedals) or 80 (80 rotations of the cycle's
      pedals) schedules. In the second part of the experiment, money was presented
      following every 20 (FR 20) or 40 (FR 40) rotations of the cycle's pedals. The
      time spent riding the cycle increased over the baseline when video clips were
      presented. No consistent differences were observed when the video clips were on
      for the entire session and when they were presented under FR 40 and FR 80
      schedules. For one out of two participants, monetary reward increased the time
      spent riding the cycle. The data suggest that reinforcement schedules are a means
      of initiating and maintaining adherence to an exercise program.

PMID- 12186240
TI  - Perceptual analysis in different voice samples: agreement and reliability.
AB  - The objective of this study was to estimate the agreement and reliability of
      voice evaluation by a group of expert listeners using the central portion of a
      sustained vowel and a fragment of connected speech as voice samples. Ratings were
      made using Wilson's Buffalo III Voice Screening Profile. Analysis showed that
      intraindividual listeners' agreement presented variability in the evaluation of
      both voice samples. In the evaluation of the central portion of the sustained
      vowel, interindividual listener agreement was moderate for breathiness, hyponasal
      resonance, and overall voice rating; in connected speech, agreement was moderate
      for most voice qualities (breathy, rough, high/low pitch, and hyponasal
      resonance). Finally, Wilson's Buffalo III Voice Screening Profile presented good
      reliability values for both voice samples, with overall voice rating achieving
      higher values (.90) than any other voice-quality variable.

PMID- 12186241
TI  - Suicidal and drug-related behaviors of rural seventh and eighth grade students.
AB  - Among 1,641 rural students in Grades 7 and 8, tobacco, alcohol, and inhalants
      were the most commonly used drugs; 281 reported suicidal thoughts, and 175 stated
      they made a plan to kill themselves during the past year.

PMID- 12186242
TI  - Changes of sleep or waking habits by age and sex in Japanese.
AB  - We analyzed the effects of age and sex on habitual sleep/wake rhythm and
      Morningness-Eveningness scores of 2,252 subjects (6-89 years) randomly selected
      in Shimonoseki, Japan. Subjects were divided into 21 age groups with a matching
      number of men and women in each age group. The most common sleep parameter
      patterns by age showed a v- or inverted v-pattern with a turning point in young
      adulthood or at the period of puberty. During the period between 6 yr. of age to
      puberty or young adulthood, the bedtimes on weekdays and weekends and the waking
      times on weekends were delayed, Morningness-Eveningness scores shifted to the
      evening type, and sleep length on weekdays decreased. After that period, across
      groups of increasing age, bedtime and waking time on weekdays and weekends became
      earlier, sleep length on weekdays and sleep latency increased, Morningness
      Eveningness scores shifted to morning type, and the number of awakenings
      increased. The number of daytime naps increased in the 16-19 yr. group, decreased
      slightly after that age group, but increased again in older groups. The weekday
      bedtimes of women above 40 yr. of age was significantly later and their sleep
      lengths significantly shorter than those of men of the same age. Average sleep
      latency was longer for women than men. The number of awakenings was larger in
      women above 50 yr. of age than men of the same age group. The turning point of
      age, gained from the two linear regressions on data for subjects that have a
      minimum sum of squared error, was between 16 and 25 yr. of age. Average phase of
      sleep/wake rhythm shifted backward and sleep length decreased in groups from age
      6 to puberty or young adulthood. After early adolescence, the average phase of
      the sleep/wake rhythm shifted forward, sleep latency became longer, and daytime
      napping increased. Number of awakenings increased rapidly for women's groups over
      40 yr. of age and for men's groups after 50 yr. of age. Sex differences in our
      research are in apparent conflict with previous data and are discussed from the
      perspective of women's social and domestic roles in Japan.

PMID- 12186243
TI  - Promoting functional activity engagement at appropriate times with people with
      multiple disabilities.
AB  - This study was aimed at teaching three persons with multiple disabilities to
      carry out functional activities at appropriate times independently. To this end,
      an electronic time system that produced vibratory alarms at preset times and a
      board with object-cues (instructions for the activities) were used. Data
      indicated that all three persons learned to perform the scheduled activities at
      the preset times independent of prompts from staff. Implications of the data and
      the combination of these activities with structured occupational periods were
      discussed.

PMID- 12186244
TI  - Qualitative analysis of lumbar stabilization using point light and normal video
      displays.
AB  - Professionals in many fields use qualitative analysis to improve human movement.
      In previous research examining the reliability of physical therapists'
      qualitative assessments of lumbar stabilization, three experienced observers
      showed substantial agreement when viewing point light displays, but only moderate
      agreement when observing normal video displays. Replication of these findings in
      a larger group of less experienced observers would strengthen the notion that
      point light displays enhance qualitative analysis. The present study examined the
      reliability of qualitative assessments of lumbar stabilization when novice
      observers made judgments from two types of video displays. 50 fourth-year
      physical therapy students viewed either normal or point light video displays to
      judge lumbar stabilization of individuals performing a floor to waist lift.
      Multirater kappa coefficients for assessments made from normal displays and point
      light displays were .30 and .46, indicating fair and moderate agreement,
      respectively. These results suggest that point light displays may enhance
      observers' visual perception of human movement.

PMID- 12186245
TI  - Parietal lobe activation in rapid, automatized naming by adults.
AB  - Three automatic naming tasks (Wiig & Nielsen, 1999) were administered to 60
      normally functioning adults. The mean time required for naming 40 single
      dimension (colors, forms, numbers, and letters) and 40 dual-dimension stimuli
      (color-form, color-number, and color-letter combinations) were compared in young
      (17-38 yr.) and older (40-68 yr.) men and women. Analysis of variance for the
      combined groups indicated significant naming-time differences for age but not for
      sex. There were no significant interaction effects. For men there was a
      significant naming time difference between age groups for forms, and for women
      for colors and forms. The sex-specific analyses indicated no significant
      differences in naming time based on age groups for color-form, color-number, or
      color-letter combinations. In a second study of adult subjects (n = 14),
      functional brain activity was measured with regional cerebral blood flow during
      the performance of the color, form, and color-form naming tasks. One subject was
      repeatedly measured during the performance of each task, whereas 13 subjects were
      measured during the performance of color-form naming. In comparison to normal
      reference values for rest and FAS verbal fluency, blood-flow measurements showed
      a consistent parietal-lobe activation during form and color-form naming, but only
      a slight activation during color naming. During all naming tasks, a significant
      frontal and frontotemporal flow decrease was seen in comparison to both rest and
      verbal fluency reference values. This functional brain activation pattern of a
      parietal increase and a frontotemporal decrease was consistently confirmed across
      subjects during the color-form naming task.

PMID- 12186246
TI  - Is controllability of imagery related to canoe-slalom performance?
AB  - This study investigated the relationship of controllability of mental imagery
      with canoe-slalom performance. Controllability of mental imagery was assessed by
      an objective test of mental rotation, the Mental Rotations Test. This test was
      administered to both elite (n = 19) and intermediate (n = 12) athletes.
      Predictive validity of the controllability test was supported by a significant
      correlation between test scores and race rank-order for the elite canoeing group
      (rs = 0.42, p<.05); however, it did not distinguish elite from intermediate
      groups (t29 = 0.98, p>.05). Researchers should attempt to evaluate vividness of
      imagery, controllability of imagery, and accuracy of reference to understand more
      fully the nature of athletes' imagery.

PMID- 12186247
TI  - Disturbance effect of music on processing of verbal and spatial memories.
AB  - The purpose of the present study was to examine the disturbance effect of music
      on performances of memory tasks. Subjects performed a verbal memory task and a
      spatial memory task in 4 sound conditions, including the presence of vocal music,
      instrumental music, a natural sound (murmurings of a stream), and no music. 47
      undergraduate volunteers were randomly assigned to perform tasks under each
      condition. Perceived disturbance was highest under the vocal music condition
      regardless of the type of task. A disturbance in performance by music was
      observed only with the verbal memory task under the vocal and the instrumental
      music conditions. These findings were discussed from the perspectives of the
      working memory hypothesis and the changing state model.

PMID- 12186248
TI  - Curriculum enrichment with self-testing activities in development of fundamental
      movement skills of first-grade children in Greece.
AB  - The purpose of this study was to investigate the effect of self-testing
      activities on the development of fundamental movement skills in first-grade
      children in Greece. Two groups of children were tested. The Control group (n = 23
      children) received the regular 12-wk. physical education school program and the
      Experimental group (n = 22 children) received a 12-wk. skill-oriented program
      with an increasing allotment of self-testing activities. The Test of Gross Motor
      Development was used to assess fundamental movement skills, while the content
      areas of physical education courses were estimated with an assessment protocol,
      based on the interval recording system called the Academic Learning Time-Physical
      Education. A 2 x 2 repeated measures analysis of variance with group as the
      between factor and testing time (pretest vs posttest) as the repeated-measures
      factor was performed to assess differences between the two groups. A significant
      interaction of group with testing time was found for the Test of Gross Motor
      Development total score, with the Experimental group scoring higher then the
      Control group. A significant main effect was also found for test but not for
      group. This study provides evidence supporting the notion that a balanced
      allotment of the self-testing and game activities beyond the usual curriculum
      increases the fundamental motor-skill development of children. Also, it stresses
      the necessity for content and performance standards for the fundamental motor
      skills in educational programs. Finally, it seems that the Test of Gross Motor
      Development is a useful tool for the assessment of children's fundamental
      movement skills.

PMID- 12186249
TI  - Geophysical variables and behavior: XCVIII. Ambient geomagnetic activity and
      experiences of "memories": interactions with sex and implications for receptive
      psi experiences.
AB  - During 96 nonsequential days over a 3-yr. period, a total of 53 men and 86 women
      were exposed only once for 30 min. to transcerebral, weak complex magnetic fields
      while they sat alone within a quiet chamber. They were asked to record the
      frequency of specific experiences after the exposure was completed. There was a
      significant interaction between sex and global geomagnetic activity for the
      incidence of experiences attributed to memories. Women reported more experiences
      attributed to "childhood memories" when geomagnetic activity was less than 20 nT,
      while men reported more of these experiences when the activity was more than 20
      nT. Re-analyses of a database of "paranormal experiences" reported by 395
      separate individuals over a 100-yr. period indicated that more men than women
      reported "precognitive experiences" on days the geomagnetic activity was above 20
      nT while women reported such experiences if the geomagnetic activity was below 20
      nT. These results suggest that these experiences, be they veridical or illusory,
      may be influenced by global geomagnetic activity that affect the neuroelectrical
      or neurochemical processes associated with memory consolidation or the
      attribution of the serial order of experiences during retrieval.

PMID- 12186250
TI  - Comparative study of eye movements in extent of central and peripheral vision and
      use by young and elderly walkers.
AB  - This study compares the visual abilities of young and elderly groups while
      walking, focusing on differences in the ranges and velocities of eye movements
      and on differences in the extent and use of their central and peripheral vision.
      On the basis of two experiments, the following differences between young and
      elderly walkers in the use of vision, as well as the effect of these differences
      on walking cadence (the number of steps per minute) were clarified. Elderly
      subjects depended more on central vision than younger subjects while they were
      walking, and their walking cadences were hindered by limited visual range. In
      contrast, younger subjects made use of both their central and peripheral vision
      while walking; the clarity of peripheral vision gave them greater control over
      the process of their walking than elderly subjects had.

PMID- 12186251
TI  - Hemispheric asymmetry in accessing word meanings: concrete and abstract nouns.
AB  - The present experiments investigated hemispheric differences in the brain in
      accessing concrete and abstract word meanings. For this purpose, an automatic
      semantic priming paradigm was used with a short stimulus onset asynchrony between
      prime and target (250 msec.) as well as a low proportion of related trials (20%).
      Analysis showed that for concrete nouns, priming effects were observed in both
      hemispheres. There was greater priming in the right hemisphere, suggesting
      hemispheric differences in accessing semantic representations of concrete nouns.
      For abstract nouns, on the other hand, priming patterns in the right hemisphere
      were identical to those in the left hemisphere, suggesting that information about
      abstract nouns projected to the right hemisphere may be transferred to the
      dominant left hemisphere for further processing.

PMID- 12186252
TI  - Commentary on "Urine alarms and prompts for fostering daytime urinary continence
      in a student with multiple disabilities: a replication study" by Lancioni, Van
      Bergen, and Furniss (2002).
AB  - Comments are made on successful use of auditory plus vibratory aids in fostering
      daytime urinary continence by a 14-yr.-old boy with multiple disabilities,
      including severe hearing loss.

PMID- 12186253
TI  - Colors associated with styles of love.
AB  - Colors associated with different love attitudes were examined using the Hendrick
      and Hendrick Love Attitudes Scale for six love styles. 143 college students rated
      the extent to which each love style reminded them of 12 colors. As expected,
      Lee's representation of the love-color analogy was not supported. Each love
      attitude was associated with relatively distinct colors.

PMID- 12186258
TI  - Regenerative medicine through mesenchymal stem cells for bone and cartilage
      repair.
AB  - Bone and cartilage defects are common features of bone fracture and joint
      diseases, such as rheumatoid arthritis or osteoarthritis, that have great social
      and economic impact on the aging occidental population. Despite progress in
      orthopedic surgery, bone and cartilage repair is a major challenge as large
      defects will not spontaneously heal. Recent investigations on the stromal
      mesenchymal stem cell (MSC) offer a new perspectivefor bone and cartilage tissue
      engineering. However, the standard offull healing is extremely demanding and may
      be achieved through the engineering of MSCs combined with scaffolds and growth
      factors as recombinant proteins, or using a gene therapy approach.

PMID- 12186259
TI  - BAFF: a novel therapeutic target for autoimmunity.
AB  - Autoimmunity results from a break in self-tolerance involving humoral and/or cell
      mediated immune mechanisms. One pathological consequence of a failure in central
      and/or peripheral tolerance is the generation of autoantibodies and subsequent
      formation of complement-fixing immune complexes that contribute to tissue damage.
      Prevailing pharmacological strategies for treating autoimmune diseases involve
      the use of broad-acting immunosuppressants that with long term use have
      associated toxicities. The current drive in drug development is towards therapies
      that target a specific biological pathway or pathogenic cell population. Recent
      discovery of the BAFF-mediated B-cell survival pathway provides a unique
      opportunity for developing focused intervention for autoreactive B-cell function.

PMID- 12186260
TI  - Suppression of inflammation and joint destruction in rheumatoid arthritis may
      require a concerted action of Th2 cytokines.
AB  - A predominance of T-helper 1 (Th1) activity and a lack of Th2 activity has been
      documented in the inflamed joints of patients with rheumatoid arthritis (RA).
      This imbalance is suggested to contribute to activation of, particularly,
      inflammatory macrophages and B-cells. Th2-mediated immunity, like atopy, is
      associated with amelioriated inflammation and joint damage in RA patients.
      Despite the potent anti-inflammatory capacities of two prominent Th2 cytokines in
      many experimental studies, clinical trials with either human IL-4 or IL-10 in RA
      patients did not lead to substantial disease suppression. Based on a thorough
      evaluation of the actions of IL-4 and IL-10 in these studies, it is hypothesized
      that disease suppression of RA may require the concerted action of suppressive
      Th2 cytokines or Th2 activity.

PMID- 12186261
TI  - Eculizumab (Alexion).
AB  - Eculizumab (5G1.1), a humanized monoclonal antibody that prevents the cleavage of
      human complement component C5 into its pro-inflammatory components, is under
      development by Alexion as a potential treatment for several chronic inflammatory
      diseases, including rheumatoid arthritis (RA) and nephritis [190673], [292328].
      In January 2002, a phase IIb trial was initiated for RA [437814]. This trial was
      ongoing in April 2002, at which time, eculizumab was also in phase II trials for
      the treatment of membranous nephritis and lupus nephritis, and in earlier stage
      clinical trials for dermatomyositis and pemphigoid [446377]. The company is also
      developing a single-chain version of this antibody, pexelizumab, for use in acute
      cardiovascular indications [188760]. In October 2000, eculizumab was granted
      Orphan Drug status by the FDA for the treatment of dermatomyositis [385057]. In
      February 2002, the product received Orphan Drug designation for its use in
      patients with membranous nephritis [440583]. In September 2001, analysts at US
      Bancorp Piper Jaffray predicted eculizumab's launch for dermatomyositis and
      pemphigus in 2003, RA and nephritis in 2004, and chronic heart failure (CHF)
      after 2006 [426537]. In March 2002, analysts at US Bancorp Piper Jaffray
      predicted that the product would have peak worldwide sales in RA of US $175
      million and US $400 million for nephritis. Sales for the RA indication are
      predicted to reach US $35 million in 2006, rising to US $110 million in 2008, and
      US $10 million in 2006, rising to US $50 million in 2008, in the US and the rest
      of the world, respectively. For the nephritis/other indication(s), sales are
      pegged at US $50 million in 2006, rising to US $200 million in 2008, and US $15
      million in 2006, rising to US $100 million in 2008, again in the US and the rest
      of the world, respectively [446992].

PMID- 12186262
TI  - Aldosterone antagonists in congestive heart failure.
AB  - The role of aldosterone in the pathophysiology of congestive heart failure (CHF)
      has long been recognized. The recent RALES (Randomized Aldactone Evaluation
      Study) trial demonstrated early reduction in morbidity and mortality using
      spironolactone, an aldosterone receptor antagonist, in combination with
      angiotensin converting enzyme (ACE) inhibitor and loop diuretic, in patients with
      heart failure. This effect of spironolactone highlighted the importance of
      understanding the contributions of the renin-angiotensin-aldosterone system
      (RAAS) in the progression of CHF, and increased interest in the use of
      aldosterone antagonists. While ACE inhibitors have had the largest impact on
      adverse events in CHF, numerous studies have shown that these drugs fail to
      completely suppress aldosterone. Blocking the effects of residual aldosterone has
      now been demonstrated to affect prognosis in these patients. This review will
      discuss the role of aldosterone in the pathophysiology of CHF, with an emphasis
      on both known and potential therapeutic benefits of aldosterone antagonism.

PMID- 12186263
TI  - Current and new drugs for the treatment of arrhythmias.
AB  - Sudden cardiac death is a leading cause of mortality in industrialized nations,
      accountingfor 50% of all cardiovascular deaths. Carefully performed randomized
      trials, technological advances and better understanding of arrhythmia mechanisms
      have resulted in improved approaches to rhythm disturbances. Risk assessment has
      to be individualized and can be approached through an analysis based upon all
      other clinical characteristics of the patient. The need for long-term therapy
      must be carefully individualized to each patient, since the severity and
      importance of symptoms are highly variable. This review will summarize the
      classification of antiarrhythmic drugs and main pharmacokinetic properties. Newer
      antiarrhythmic drugs either block a specific ionic current (eg, dofetilide
      induced blockade of the rapidly activating component of the delayed rectifier
      potassium current) or block multiple ionic channels (eg, ibutilide and azimilide)
      in order to prolong atrial and ventricular action potentials without other
      specific pharmacological effects. Additionally, this manuscript reviews the newer
      class III agents' effectiveness in treating atrial and ventricular arrhythmias,
      and the development of novel antiarrhythmic drugs that act specifically to alter
      cell communication.

PMID- 12186264
TI  - Amiodarone in the prevention and treatment of arrhythmia.
AB  - There is good evidence that amiodarone is effective against a variety of
      arrhythmias and that it may be superior to other drugs in some settings. Because
      of its proven efficacy and safety, amiodarone is currently the leading
      antiarrhythmic drug. The electrophysiological actions of amiodarone are complex
      and not completely understood. It is generally classified as a Vaughan-Williams
      class III agent, prolonging repolarization by inhibition of outward potassium
      channels. Amiodarone is particularly useful because its safety has been clearly
      demonstrated by a large body of evidence, including several randomized trials.
      Compared with many other antiarrhythmic drugs, amiodarone causes few
      cardiovascular adverse effects; however, its overall tolerance is limited by
      considerable non-cardiac toxicity. Although amiodarone will continue to give way
      to the implantable cardioverter defibrillator (ICD) as primary therapy for many
      patients presenting with sustained ventricular tachycardia (VT) or ventricular
      fibrillation (VF), it is likely that the use of amiodarone in ICD patients will
      continue to prevent ICD discharges. Evaluation of combined use of amiodarone and
      ICD may provide the first opportunity to conduct a placebo-controlled trial of
      amiodarone efficacy against VT recurrence. Pharmacological therapy remains the
      major approach to management of atrial fibrillation (AF), and the use of
      amiodarone is likely to increase in future years. This review will analyze the
      evidence that amiodarone is a safe and effective antiarrhythmic drug.

PMID- 12186265
TI  - Sudden cardiac death: from molecular biology and cellular electrophysiology to
      therapy.
AB  - Sudden cardiac death (SCD) is one of the most serious problems of clinical
      cardiology and public health, because of its unexpected and sudden occurrence and
      poor response to resuscitation. Until recently, the many cases of SCD, apart from
      those caused by coronary heart diseases (CHD), were unexplained. Advances in
      methodology, especially molecular biology techniques and cellular
      electrophysiology, ie, patch clamp technique, revealed several mutations of
      sodium and potassium cardiac ion channels as a background for serious arrhythmia
      and consequently SCD in cases earlier determined as idiopathic ventricular
      fibrillation.

PMID- 12186266
TI  - S-0139 (Shionogi).
AB  - Shionogi and GlaxoSmithKline (GSK), as the joint venture company Shionogi
      GlaxoSmithKline Pharmaceuticals LLC, are developing S-0139 (SB-737004), an
      endothelin-A (ETA) antagonist, for the potential treatment of hemorrhagic and
      ischemic stroke [223386], [252007], [426822], [426830]. By 1999, the compound was
      in phase II trials in Japan for stroke [348554]; phase II trials were ongoing in
      March 2002 [446957]. As of May 2000, Shionogi was preparing to develop the drug
      in the US and Europe [370602]. As of May 2001, a phase I European trial was in
      preparation [410912]; which was underway by November 2001 [429990]. In July 2001,
      Shionogi and GSK signed a letter of intent to create a joint venture that was
      initially to have exclusive rights to develop and commercialize four compounds
      contributed by Shionogi and one by GSK, including S-0139 14167621. The agreement
      wasfinalized in October 2001 [426569], [426822]. In August 1999, Lehman Brothers
      gave S-0139 a 10% probability of reaching the market with an expected launch in
      2005. Sales were expected to peak at US $50 million in 2012 [349228].

PMID- 12186267
TI  - BMS-193884 and BMS-207940 Bristol-Myers Squibb.
AB  - Bristol-Myers Squibb is developing BMS-193884, an oral endothelin antagonist, for
      the potential treatment of congestive heart failure (CHF) and pulmonary
      hypertension [206604]. The compound entered phase I trials in November 1996
      [242721] and had progressed to phase II trials [399460], [441398]. Structural
      modifications led to the development of a second-generation analog, BMS-207940, a
      biphenylsulfonamide endothelin A receptor-selective antagonist, and the probable
      discontinuation of the first clinical candidate, BMS-193884 [446511]. By April
      2002, BMS-207940 was in phase I trials [446511]. By March 2002, filing for NDA
      was expected to take place in 2004 at the earliest [452734].

PMID- 12186268
TI  - Positive modulators of AMPA receptors as a potential treatment for schizophrenia.
AB  - There is a consensus that current treatments of schizophrenia do not offer
      satisfactory efficacy for negative and cognitive symptoms. Recently, the
      dopaminergic hyperfunction hypothesis of schizophrenia has been enriched by the
      addition of the glutamatergic hypofunction concept. Accordingly, agents enhancing
      glutamatergic transmission should provide benefit in psychosis. In fact, some
      preclinical studies suggest that positive modulators of alpha-amino-3-hydroxy-5
      methyl-4 isoxazolepropionic acid (AMPA) receptors, previously developed mainly
      for dementia, may fulfill such expectations. These agents attenuate various
      biochemical or behavioral effects produced by amphetamine or methamphetamine and
      enhance the action of antipsychotics. More importantly, preliminary clinical
      studies with the most advanced member of this class, CX-516(Cortex
      Pharmaceuticals Inc), indicate beneficial action on negative and cognitive
      symptoms as an add-on treatment t o clozapine. If these observations are
      confirmed in a larger scale clinical trial, this approach could be a major
      improvement in the treatment of schizophrenia.

PMID- 12186269
TI  - Glycine modulators in schizophrenia.
AB  - N-methyl-D-aspartate (NMDA) receptor dysfunction may play a key role in the
      pathophysiology of schizophrenia. Recent studies have investigated the ability of
      NMDA/glycine-site modulators to ameliorate persistent negative and cognitive
      symptoms. Several full or partial glycine-site agonists, including glycine, D
      serine and D-cycloserine, have shown effectiveness in small-scale clinical
      trials. Glycine levels in brain are regulated by GLYT1-type glycine transporters.
      Recently developed glycine transport inhibitors (GTI) have preclinical behavioral
      effects similar to those of glycine or D-serine, and may represent a 'next
      generation' approach to the treatment of the persistent negative and cognitive
      symptoms of schizophrenia.

PMID- 12186270
TI  - New antipsychotic agents for schizophrenia: pharmacokinetics and metabolism
      update.
AB  - The so-called atypical antipsychotics undergo extensive metabolism, except for
      amisulpride, which is substantially excreted unchanged. Risperidone is oxidized
      by CYP2D6/CYP3A4 and iloperidone is reduced by cytosolic enzymes, although
      CYP1A2, CYP2E1 and CYP3A4 are involved as well. Olanzapine is both conjugated and
      oxidized (mainly by CYP1A2), while quetiapine and zotepine primarily undergo
      CYP3A4-mediated oxidation. Ziprasidone pathways include aldehyde oxidase-mediated
      reduction and CYP3A4-mediated oxidation. The main metabolites of risperidone,
      zotepine and possibly perospirone and ziprasidone contribute to the parent drug's
      effect. Information is limited, however, on some promising antipsychotics in the
      pipeline.

PMID- 12186271
TI  - CX-516 Cortex pharmaceuticals.
AB  - CX-516 is one of a series of AMPA modulators under development by Cortex, in
      collaboration with Shire and Servier, for the potential treatment of Alzheimer's
      disease (AD), schizophrenia and mild cognitive impairment (MCI) [234221]. By June
      2001, CX-516 was in phase II trials for both schizophrenia and attention deficit
      hyperactivity disorder (ADHD) [412513]. A phase II trial in fragile X syndrome
      and autism was expected to start in May 2002 [449861]. In October 2001, Cortex
      was awarded a Phase II SBIR grant of $769,818 from the National Institutes of
      Mental Health to investigate the therapeutic potential of AMPAkines in
      schizophrenia. This award was to support a phase IIb study of CX-516 as a
      combination therapy in schizophrenia patients concomitantly treated with
      olanzapine. The trial was to enroll 80 patients and employ a randomized, double
      blind, placebo-controlled design in which the placebo group was to receive
      olanzapine plus placebo and the active group was to receive olanzapine plus CX
      516 [425982]. In April 2000, Shire and Cortex signed an option agreement in which
      Shire was to evaluate CX-516for the treatment of ADHD. Under the terms of the
      agreement, Shire would undertake a double-blind, placebo-controlled evaluation of
      CX-516 involving ADHD patients. If the study proved effective, Shire would have
      the right to convert its option into an exclusive worldwide license for the
      AMPAkines for ADHD under a development and licensing agreement. Should Shire
      elect to execute this agreement, Shire would bear all future developmental costs
      [363618]. By February 2002, Cortex and Servier had revealed their intention to
      begin enrolment for an international study of an AMPAkine compound as a potential
      treatment for MCI in the near future. Assuming enrollment proceeded as
      anticipated, results were expected during the second quarter of 2003 [439301]. By
      May 2002, phase II trials were underway [450134]. In March 2002, Cortex was
      awarded extended funding under the University of California BioSTAR projectfor
      the research project: 'Ampakine modulation of brain neurotrophin expression: a
      novel therapeutic strategy'. This funding was expected to amount to $193,000 over
      a two-year period [444872].

PMID- 12186272
TI  - Immunotoxins in cancer therapy.
AB  - Several antibodies have now been approved for the therapy of cancer. Two of
      these, rituximab (Rituxan) and alemtuzumab (CAMPATH; ILEX Oncology Inc), are
      capable of inducing cell death and tumor regressions when given alone. The third,
      trastuzumab (Herceptin), is not very effective by itself, but does potentiate the
      activity of paclitaxel (Taxol) and other chemotherapeutic agents. Unfortunately,
      most antibodies do not kill cancer cells unless they are armed with a cytotoxic
      agent, such as a radioisotope, a cytotoxic drug, or a protein toxin. Each of
      these have advantages and disadvantages.

PMID- 12186273
TI  - Cetuximab (Imclone/Merck/Bristol-Myers Squibb).
AB  - ImClone, in collaboration with licensees, Merck KGaA and Bristol-Myers Squibb
      (BMS), are developing cetuximab, a chimeric monoclonal antibody that blocks the
      epidermal growth factor receptor, for the potential treatment of various cancers,
      including colorectal, and head and neck tumors [179103]. The companies are
      evaluating the product both as a single agent, and in combination with radiation
      and a variety of chemotherapeutic agents. By January 2002, phase III trials had
      been initiated in head and neck cancer, and phase II trials were ongoing for
      colorectal and other cancers [427710], [437833]. In November 2001, ImClone
      completed the filing of a rolling BLA with the FDA for cetuximab in combination
      with irinotecan to treat irinotecan-refractory colorectal cancer. In December
      2001, however, the FDA advised ImClone that its BLA was not acceptable for
      filing. In January 2002, it was reported that resubmission of the BLA was
      expected within 3 months [434999], and by February 2002, ImClone was expecting to
      use data from an ongoing phase II study in colorectal cancer patients conducted
      by Merck KGaA. In March 2002, Merck had anticipated European launch in 2003
      [444653]; however, in April 2002, Merck reported that it was delaying its
      application to the European Agency for the Evaluation of Medicinal Products from
      the last half of 2002 to the first half of 2003, so that it could primarily
      include its own colorectal cancer data rather than ImClone's data. European
      launch was thus expected in 2004 [449226]. In May 2002, Lehman Brothers predicted
      global peak sales of US $2 billion [454652], while in the same month, Bear
      Stearns estimated that sales for Merck KGaA would reach 285 million Euros in 2007
      [453500].

PMID- 12186274
TI  - Meningococcal vaccines.
AB  - Neisseria meningitidis is one of the leading infectious causes of death in
      children under five years old in industrialized countries, and most cases can be
      attributed to five disease-causing serogroups: A, B, C, Y and W135. Meningococcal
      vaccine development began in the 1930s with killed whole-cell and exotoxin
      vaccines, but widespread use of polysaccharide vaccines did not begin until the
      1970s. Serogroup A, C, Y and W135 polysaccharides are all included in vaccines
      for travellers, other high risk groups and control of outbreaks, but have limited
      immunogenicity and effficacy in childhood. Protein-polysaccharide conjugate
      vaccines overcome this problem and offer the possibility of protection in early
      childhoodfrom serogroup A, C, Y and W135. An effective serogroup B vaccine
      remains elusive and the greatest challengefor vaccine developers.

PMID- 12186275
TI  - Vaccines for Chlamydia trachomatis infections.
AB  - Members of the genus, Chlamydia, are obligate intracellular bacteria that have a
      unique developmental cycle. These organisms are widespread in nature and are
      common human pathogens. In this review, we describe new data related to the
      characterization of acquired immunity to Chlamydia trachomatis that is relevant
      to vaccine development. We also discuss recent work on vaccine candidates against
      this ubiquitous pathogen.

PMID- 12186276
TI  - Hepagene (PowderJect).
AB  - Celltech Group (formerly Medeva) developed Hepagene, a recombinant polyvalent
      vaccine with potential activity against hepatitis B virus infections [353474]. In
      September 2000, PowderJect acquired the product as part of its acquisition of
      Celltech's vaccine manufacturing business [381557]. In July 2001, PowderJect
      reported that evaluation was nearing completion. At this time, the company
      expected to launch the vaccine in the coming months [443490]. Hepagene is a
      polyvalent vaccine with S, pre-S1 and pre-S2 hepatitis B epitopes forming the
      basis of its antigenicity. Additionally, these surface markers have been
      glycosylated in order to resemble the live virus more closely [254780]. By June
      2000, Celltech and PowderJect were evaluating Hepagene, utilizing PowderJect's
      needle-less injection technology [379536]. In December 1999, Lehman Brothers
      predicted that the product had a 50% chance of reaching the treatment (rather
      than prevention) market, with potential peak sales of US $600 million [352078].

PMID- 12186277
TI  - Arilvax (PowderJect).
AB  - Celltech (formerly Medeva) had developed Arilvax, a single-dose, live, attenuated
      vaccine for the prevention of yellow fever, which the company launched in Europe.
      However, in October 2000, PowderJect acquired the vaccine as part of its
      acquisition of Celltech's vaccine business [381557], [384374]. In July 2001,
      PowderJect expected to re-launch Arilvax in the UK and, in the near future,
      Europe, following a manufacturing upgrade [414453], [443490]. By May 2000,
      Acambis (formerly Peptide Therapeutics), was developing the vaccine in the US
      under an exclusive license and phase III trials were underway [341301], [366663].
      By September 2000, preparation for a BLA in the US had begun [382969]. By
      September 2001, the BLA submission was expected by mid-2002 [422760], [443490].
      In September 1999, Peptide Therapeutics was predicting a US launch in the first
      half of 2001 with expected sales of around US $25 million per annum [340078],
      [341301].

PMID- 12186278
TI  - Varlirix (GlaxoSmithKline).
AB  - GlaxoSmithKline (formerly SmithKline Beecham) has developed and launched
      Varilrix, a preparation of live, attenuated Oka-strain varicella zoster virus,
      for immunization against varicella zoster infections [455138]. By the end of
      1998, Varilrix was available in a few European countries and in India [284490],
      [455138]. By 2001, the vaccine was also available in Brazil and Hong Kong
      [396267].

PMID- 12186279
TI  - Bioaccumulation of trace metals in the calanoid copepod Metridia gerlachei from
      the Weddell Sea (Antarctica).
AB  - Bioaccumulation of Cd, Co, Cu, Ni, Pb and Zn in the Antarctic calanoid copepod
      Metridia gerlachei (Giesbrecht 1902) was investigated during a cruise of RV
      'Polarstern' to the Weddell Sea, primarily to provide information on accumulation
      strategies for the metals tested. With the sole exception of Cd, the copepod
      accumulated metals during exposure and depurated them in uncontaminated seawater.
      The process of uptake and depuration was successfully described by a hyperbolic
      model, leading to significant estimations of the following experimental
      bioconcentration factors (BCFs): 210 (Co), 3430 (Cu), 3060 (Ni), 670 (Pb) and
      2090 (Zn). Furthermore, we provide an approach to evaluate the sensitivity of
      Metridia gerlachei as a biomonitor of water-borne metals in the field; the
      results indicate minimal increments in ambient exposure concentrations of: 0.5
      microg Cu l(-1), 0.8 microg Ni l(-1), 0.6 microg Pb l(-1) and 0.2 microg Zn l(
      1), suggesting a high sensitivity of M. gerlachei for biomonitoring.

PMID- 12186280
TI  - Quality of dredged material in the River Seine basin (France). I. Physico
      chemical properties.
AB  - In rivers, sediments are frequently accumulating persistent chemicals, especially
      for those that are more contaminated as a consequence of pressure related to
      environmental pollution and human activity. The Seine river basin (France) is
      heavily polluted from nearby industrial activities, and the urban expansion of
      Paris and its suburbs within the Ile de France region and the sediments present
      in the Seine river basin are contaminated. To ensure safe, navigable waters,
      rivers and waterways must be dredged. In this paper, the quality of the sediment
      dredged in 1996, 1999 and 2000 is discussed. Physico-chemical characteristics of
      the sediment itself and of the pore-water are presented. Seine basin sediments
      show very diverse compositions depending on the sampling site. Nevertheless, a
      geographic distribution study illustrated that the Paris impact is far from being
      the only explanation to this diversity, the quality of this sediment is also of
      great concern. The sediment once dredged is transported via barges to a wet
      disposal site, where the dredged material is mixed with Seine water in order to
      be pumped into the receiving site. This sort of dumping might be responsible for
      the potential release of contaminants to the overlying water from the
      significantly contaminated sediments.

PMID- 12186281
TI  - Assessment of gully pot management strategies for runoff quality control using a
      dynamic model.
AB  - A gully pot is the first entry point of road runoff into an urban drainage
      network. Pots are extensively used to trap solids from runoff in order to
      avoid/minimise the problems associated with sediment deposition in the downstream
      drainage structures or receiving waters. Here we briefly describe the different
      modules of a dynamic gully pot model developed to assess the impact of a series
      of management practice scenarios on the quality of runoff discharged through the
      pots. Runoff quality was modelled in terms of suspended solids (SS), chemical
      oxygen demand (COD), dissolved oxygen (DO) and ammonium. The model has the
      flexibility to represent the impact of various interactions between physical and
      biochemical processes occurring in a pot during wet and dry weather conditions,
      respectively. The simulation results show that the pots are effective at
      retaining solids, but their role with regard to reduction of dissolved pollutants
      is almost neutral. Model predictions, as against common perception, show that
      frequent pot cleaning does not significantly improve the runoff quality. However,
      considerably improved solid retention is possible if larger pots with modified
      geometry are introduced into the drainage system.

PMID- 12186282
TI  - Drugs and personal care products as ubiquitous pollutants: occurrence and
      distribution of clofibric acid, caffeine and DEET in the North Sea.
AB  - An analytical method is presented, which allows the simultaneous extraction of
      neutral and acidic compounds from 20-L seawater samples at ambient pH
      (approximately 8.3). It is based on a solid-phase extraction by means of a
      polystyrene-divinylbenzene sorbent and gas chromatographic-mass spectrometric
      detection, and provides detection limits in the lower pg/L range. The method was
      applied to the screening of samples from different North Sea areas for clofibric
      acid, diclofenac, ibuprofen, ketoprofen, propyphenazone, caffeine and N,N-diethyl
      3-toluamide (DEET). Whereas clofibric acid, caffeine and DEET showed to be
      present throughout the North Sea in concentrations of up to 1.3, 16 and 1.1 ng/L,
      respectively, propyphenazone could only be detected after further clean-up.
      Diclofenac and ibuprofen were found in the estuary of the river Elbe (6.2 and 0.6
      ng/L, respectively) but in none of the marine samples. Ketoprofen was below the
      detection limit in all samples.

PMID- 12186283
TI  - Effects of surface run-off on the transport of agricultural chemicals to ground
      water in a sandplain setting.
AB  - An experiment was conducted at a depressional (lowland) and an upland site in
      sandy soils to evaluate the effects of surface run-off on the transport of
      agricultural chemicals to ground water. Approximately 16.5 cm of water was
      applied to both sites during the experiment, representing a natural precipitation
      event with a recurrence interval of approximately 100 years. Run-off was
      quantified at the lowland site and was not detected at the upland site during the
      experiment. Run-off of water to the lowland site was the most important factor
      affecting differences in the concentrations and fluxes of the agricultural
      chemicals between the two sites. Run-off of water to the lowland site ppears to
      have played a dual role by diluting chemical concentrations in the unsaturated
      zone as well as increasing the concentrations at the water table, compared to the
      upland site. Concentrations of chloride, nitrate and atrazine plus metabolites
      were noticeably greater at the water table than in the unsaturated zone at both
      sites. The estimated mass flux of chloride and nitrate to the water table during
      the test were 5-2 times greater, respectively, at the lowland site compared to
      the upland site, whereas the flux of sulfate and atrazine plus metabolites was
      slightly greater at the upland site. Results indicate that matrix flow of water
      and chemicals was the primary process causing the observed differences between
      the two sites. Results of the experiment illustrate the effects of heterogeneity
      and the complexity of evaluating chemical transport through the unsaturated zone.

PMID- 12186284
TI  - Risso's dolphin (Grampus griseus) stranding on the coast of Israel (eastern
      Mediterranean). Autopsy results and trace metal concentrations.
AB  - The stranding of Risso's dolphin (Grampus griseus) on the Mediterranean coast of
      Israel is reported in this study. High concentrations of trace metals (Hg, Cd,
      Zn, Fe and Se) were found in the various tissues analyzed, while Cu and Mn
      concentrations were naturally low. The specimen was found alive, but died a day
      later. The cause of death was attributed to bacterial bronchopneumonia in
      combination with endotoxemia, resulting in disseminated intravascular
      coagulation. Plastic bags found in its stomach contributed to the dolphin's poor
      physical condition. No connection was found between the high concentrations of
      trace metals in the internal organs and the cause of death. It is assumed that
      the high concentrations were a result of the high trophic level of this species,
      its diet and its advanced age. Anthropogenic influence could not be assessed due
      to the sparse database of trace metals for this species, in particular knowledge
      of the natural levels.

PMID- 12186285
TI  - Cadmium toxicity to ringed seals (Phoca hispida): an epidemiological study of
      possible cadmium-induced nephropathy and osteodystrophy in ringed seals (Phoca
      hispida) from Qaanaaq in Northwest Greenland.
AB  - The Greenland marine food chains contain high levels of cadmium, mercury and
      selenium. Concentrations of cadmium in the kidney of ringed seals (Phoca hispida)
      from the municipalities of Qaanaaq and Upernavik (Northwest Greenland) are among
      the highest recorded in the Arctic. The purpose of the study was to determine
      whether cadmium-induced damage in the kidneys and the skeletal system could be
      detected among 100 ringed seals from Northwest Greenland. The cadmium
      concentrations in the kidney cortex ranged from 0 to 248 microg/g wet weight
      (mean=44.5, N=100) in the 99 kidneys examined. Experience from cadmium-poisoned
      humans and laboratory mammals indicates that concentrations above 50-200 microg/g
      wet wt. may induce histopathological changes. Overall, 31 of the ringed seals had
      cadmium concentrations in the kidney cortex above 50 microg/g wet wt., 11 had
      concentrations above 100 and one had a concentration above 200 microg/g wet wt.
      Obvious histopathological changes (categorised mainly as glomerulonephritis) were
      found in 10 of the seals; however, none of these changes could be attributed to
      cadmium-induced renal damage (mainly tubulopathy) as described for other species.
      Damage to the proximal kidney tubules is known to induce demineralisation of the
      skeletal system (Fanconi's syndrome). Therefore, the three lowest lumbar
      vertebrae were scanned in 91 seals to measure the content of calcium. The 10
      cases of nephropathy could neither be linked to the degree of mineralisation of
      the skeleton nor to the cadmium concentrations. Furthermore, the degree of
      mineralisation of the skeleton was not correlated with the cadmium concentration,
      age or sex. It can therefore be concluded that despite high levels of cadmium,
      none of the ringed seals showed any signs of cadmium-induced nephropathy or
      osteodystrophy. This might be explained by the composition of the ringed seals
      diet, which contains high levels of vitamin D, calcium, phosphorus, zinc,
      selenium and protein. These elements are all likely to counteract cadmium-induced
      damage. It is speculated that ringed seal are not particularly vulnerable to
      osteodystrophy, due to their continuous growth (bone mineralisation) throughout
      life and the oestrogen hormonal activity of females throughout life.

PMID- 12186286
TI  - Heavy metal contamination of the soils used for stocking raw materials in the
      former ILVA iron-steel industrial plant of Bagnoli (southern Italy).
AB  - The total contents and the chemical and mineralogical forms of the metals Fe, Al,
      Cu, Co, Cr, Pb, Zn, Ni and Mn in the horizons of a soil profile, representative
      of an area devoted to stocking raw materials in the dismantled iron-steel
      industrial plant of ILVA of Bagnoli (Naples), were studied by physical and
      chemical methods. The geological setting of the study area is the result of
      volcanic activity in the Phlegrean Fields, a group of polygenic volcanoes to the
      west of Naples, which give rise to the parent soil material. Soil morphology
      appeared to be strongly disturbed by the occurrence and stratification of
      materials used in the industrial process. Fine sediments illuviation down the
      profile resulted in the occurrence of silt and clay coatings. The total contents
      of Cu, Co, Cr, Pb, Zn and Ni, in the whole soil samples, especially in the
      surface layers, were above the regulatory levels (Cu 120, Co 20, Cr 150, Pb 100,
      Zn 150, Ni 120 mg kg(-1)) stated by the Italian Ministry of Environment for soils
      in public, private and residential areas, and below the levels (Cu 600, Co 250,
      Cr 800, Pb 1000, Zn 1500, Ni 500 mg kg(-1)) outlined for soils and subsoils of
      industrial and commercial areas (Gazzetta Ufficiale della Repubblica Italiana,
      1999). Speciation of heavy metals and the determination of the different chemical
      pools in the fraction < 2 mm identified the large presence of elements trapped in
      the mineralogical structure of oxides and silicates and occluded in easily
      reducible manganese or iron oxides. A constant amount of Cu was associated with
      organic compounds. A significant amount of Zn (> 20%) was extracted in diluted
      acetic acid solution, indicating that the element was present in a more readily
      and potentially available form. In the clay fraction (< 2 microm) heavy metals
      were associated with both amorphous and crystalline iron forms. The presence of
      iron-rich clay coatings was evident in the illuvial pores of deeper horizons.
      Enrichment in Cu, Co, Cr and Zn of the coatings was observed. Possible
      translocation of metals down through the soil profile mainly bound to fine
      particles of relatively inert forms of iron is hypothesised. The dispersion in
      water of the clay fraction resulted in an average percentage dispersion of
      approximately 20% with a peak of 41.7% at 68-72 cm depth. Magnetite, goethite,
      hematite, calcite and quartz mixed with K-feldspars, clynopyroxenes and mica
      occurred in the coarse sand fractions (2-0.2 mm) of the soil samples from all the
      surface horizons. Talcum and goethite together with clay minerals at 1.4 nm,
      kaolinite and illite were found in the clays (< 2 microm).

PMID- 12186287
TI  - Comprehensive characterization of engine deposits from fuel containing MMT.
AB  - Combustion chamber deposits from a 1996 GM3800 engine operating on a base fuel or
      the base fuel containing the organometallic antiknock additive
      methylcyclopentadienyl manganese tricarbonyl were examined. Scanning Electron
      Microscopy and Energy Dispersive X-ray spectroscopic analysis were performed to
      identify the morphology and the bulk chemical composition. Glow-Discharge Mass
      Spectrometry and X-ray Diffraction analyses were also used to characterize the
      bulk chemical composition and crystalline structure of the deposits. In addition,
      X-ray photoemission and X-ray photoabsorption spectra for the deposits were
      compared to a series of Mn compounds to model and aid quantification of the
      constituents. Results reveal a mixture of Ca-sulfate, Mn-phosphate and Mn-oxide
      in the bulk of the deposits and a mixture of Mn-sulfate, Mn-phosphate and Mn
      oxide on the surface of the deposits.

PMID- 12186288
TI  - Burden of organochlorine pesticides in blood and its effect on thyroid hormones
      in women.
AB  - Man has utilized a wide variety of pesticides to combat the crop pests and
      vectors of human diseases. However, in this process, he has overlooked the darker
      side of these noxious chemicals, the concentrations of which have reached the
      environment and pose serious threats, such as mutagenesis, teratogenesis,
      carcinogenesis and endocrine dysfunction in various components of the ecosystem.
      The present study was planned to assess the burden of organochlorine pesticides
      and their influence on thyroid function in women. The study included a total of
      123 women from Jaipur City who visited the Thyroid clinic in SMS Medical College
      and Hospital. One hundred women showed normal thyroid hormone levels while the
      remaining 23 women had depleted T4 and high TSH levels. The qualitative and
      quantitative estimation of organochlorine pesticides was carried out by gas
      chromatography. Out of the analyzed pesticides, the concentration of p,p'-DDT and
      its metabolites was higher in all the subjects, but dieldrin was found to be
      significantly high in the hypothyroid women. The correlation analysis for
      dieldrin and depleted T4 levels in hypothyroid women elicited an inverse
      relationship between them.

PMID- 12186289
TI  - Arsenic pollution at the industrial site of Reppel-Bocholt (north Belgium).
AB  - An industrial site, polluted with As and heavy metals, was investigated by
      combining chemical (sequential extractions and pHstat leaching tests), physical
      and mineralogical characterization of soil samples and slag fragments, and by the
      analysis of soil porewater aimed at assessing the distribution, speciation and
      mobility of heavy metals and As. On the site itself, arsenic concentrations up to
      3.6% in surficial soil samples and up to 22% in slag fragments were found,
      together with elevated concentrations (percentage level) of Cu, Co, Ni, Zn and
      Pb. High concentrations of arsenic (up to 38,000 microg/l) and heavy metals (up
      to 1700 microg/l Cu and 4700 microg/l Zn) were also found in the in situ sampled
      soil porewater, highlighting the considerable availability of As, Zn and Cu for
      uptake by plants and leaching to the ground water. Sequential extractions also
      indicated a high availability of arsenic and copper in most samples and slag
      fragments of the industrial site, although poorly reactive phases were
      encountered as well. pHstat leaching tests confirmed that the present leaching of
      contaminants is alarming. Moreover, soil acidification will enhance the leaching
      of contaminants, emphasizing that remediation of the industrial site is urgent.
      Small scale variability of total metal concentrations and metal speciation, both
      in the horizontal and vertical direction, and the occurrence of a camouflage
      layer underline the importance of elaborate sampling for pollution assessment on
      an industrial site.

PMID- 12186290
TI  - Comparison of the lead 168-nm and 220-nm analytical lines in high iron and
      aluminium matrices by inductively coupled plasma-optical emission spectrometry.
AB  - Virtually all photomultiplier-based inductively coupled plasma spectrometers
      (ICPS) use the lead (Pb) 220.3-nm analytical line, even though it has severe
      background continuum and interelement interference from the aluminium (Al) 220.4
      nm line, and background shift due iron (Fe). Many Pb analytical lines above 220
      nm are unsuitable due to poor detection limits. There are no reports in the
      literature on the use of Pb analytical lines below 220 nm, especially the 168.2
      nm line recommended by Spectro Analytical (Kleve, Germany). The Pb 168-nm
      analytical line has a superior detection limit and is less prone to matrix,
      background continuum radiation and inter-element interference from high
      concentrations of Al and Fe compared to the Pb 220-nm analytical line. This has
      been demonstrated by the better precision and accuracy of analysis of soils
      containing high levels of Al and Fe.

PMID- 12186291
TI  - Distribution of heavy metals in sediments of the Venice Lagoon: the role of the
      industrial area.
AB  - We sampled eighteen stations in the lagoon and nine in the canals of the
      industrial area of Porto Marghera. At each lagoon site a short core, 10 cm long,
      was taken and immediately extruded to obtain four slices 2.5 cm thick. Surficial
      sediment samples from the canals were 2-8 cm thick. Samples were analysed for As,
      Cd, Hg, Pb and Zn after acid extraction. Maximum values are seen in sediments
      taken from the oldest part of the industrial area (up to 132, 70, 48, 929, 8295
      microg g(-1) for As, Cd, Hg, Pb and Zn, respectively), whereas the highest
      concentrations in the lagoon are much lower (25, 5.0, 2.3, 114, 1115 microg g(-1)
      for As, Cd, Hg, Pb and Zn, respectively). Metal distributions are not driven by
      sediment characteristics, such as grain size composition and organic carbon
      content: the strong gradients reflect the relative importance of the sources. In
      fact, a series of factories have been treating minerals for many years for the
      production of metals and chemicals. Concentration-depth profiles in lagoon
      sediments suggest that the contamination is decreasing, thus confirming the
      trends shown by previous core data. Since the release of metals from the
      industrial plants has been reduced, the polluted sediments stored in the
      industrial canals are presently the most likely source of toxic metals to the
      lagoon environment. The influence of this source can be seen in the still high
      levels found in the lagoon sample closest to the industrial area.

PMID- 12186292
TI  - Characterization of emissions from burning incense.
AB  - The primary objective of this study was to improve the characterization of
      particulate matter emissions from burning incense. Emissions of particulate
      matter were measured for 23 different types of incense using a cyclone/filter
      method. Emission rates for PM2.5 (particulate matter less than 2.5 microm in
      aerodynamic diameter) ranged from 7 to 202 mg/h, and PM2.5 emission factors
      ranged from 5 to 56 mg/g of incense burned. Emission rates were also determined
      using an electrical low pressure impactor (ELPI) and a small electrostatic
      precipitator (ESP), and emission rates were compared to those determined using
      the cyclone/filter method. Emission rates determined by the ELPI method were
      consistently lower than those determined by the cyclone/filter method, and a
      linear regression correlation was found between emission rates determined by the
      two methods. Emission rates determined by the ESP method were consistently higher
      than those determined by the cyclone/filter method, indicating that the ESP may
      be a more effective method for measuring semivolatile particle emissions. A
      linear regression correlation was also found between emission rates determined by
      the ESP and cyclone/filter methods. Particle size distributions were measured
      with the ELPI, and distributions were found to be similar for most types of
      incense that were tested. Size distributions by mass typically ranged from
      approximately 0.06 to 2.5 microm in aerodynamic diameter, with peak values
      between 0.26 and 0.65 microm. Results indicated that burning incense emits fine
      particulate matter in large quantities compared to other indoor sources. An
      indoor air quality model showed that indoor concentrations of PM25 can far exceed
      the outdoor concentrations specified by the US EPA's National Ambient Air Quality
      Standards (NAAQS), so incense smoke can pose a health risk to people due to
      inhalation exposure of particulate matter. Emissions of carbon monoxide (CO),
      nitric oxide (NO), and sulfur dioxide (SO2) were also measured for seven types of
      incense. Emission rates of the gaseous pollutants were sufficient to cause indoor
      concentrations, estimated using the indoor air quality model, to exceed the
      outdoor concentrations specified by the NAAQS under certain conditions. However,
      the incense samples that were tested would fill a room with thick smoke under
      these conditions.

PMID- 12186293
TI  - 137Cs and 40K soil-to-plant relationship in a seminatural grassland of the Giulia
      Alps, Italy.
AB  - To examine the soil-to-plant transfer of 137Cs and 40K, we performed a study
      based on sampling of natural soil and plants from an alpine pasture site situated
      in the Giulia Alps, Italy, during July 1997. High 137Cs activity was present in
      the upper most soil layer, and decreased one order of magnitude at a depth of 10
      cm. An opposite gradient was observed for 40K. Simultaneous sampling of soil and
      plant material was performed in order to analyse transfer factor (TF) values. In
      spite of homogeneous 137Cs activities in soil, grass samples showed a high
      variability. A negative correlation was detected between 40K- and 137Cs
      activities in plants. TF values for 137Cs were highly variable, thus suggesting
      that this parameter would be independent of 137Cs soil activity. Lower
      variability was observed for 40K TFs values. Our results suggest that TFs are
      highly variable parameters that appear to be independent on radionuclide soil
      activity. Because soil and plant characteristics strongly affect TF values,
      caution is necessary when TF values are used as the sole parameter to predict
      radionuclide uptake by plants in semi-natural ecosystems.

PMID- 12186294
TI  - Arsenic, Sb and Bi contamination of soils, plants, waters and sediments in the
      vicinity of the Dalsung Cu-W mine in Korea.
AB  - The objective of this study is to investigate environmental contamination derived
      from metalliferous mining activities. In the study area, the Dalsung Cu-W mine,
      soils, various crop plants, stream waters, sediments and particulates were
      sampled in and around the mine and analyzed for As, Sb and Bi by ICP-AES with a
      hydride generator. In addition, soil pH, cation exchange capacity, loss-on
      ignition and soil texture were also measured. Concentrations of As, Sb and Bi in
      surface soils sampled in the mine dump sites averaged 2500, 54 and 436 microg g(
      1), respectively. Relatively lower concentrations, however, were found in soils
      from alluvial and high land sites and household garden sites. Arsenic, Sb and Bi
      contents in plant samples varied depending upon their species and parts, with
      higher concentrations in spring onions, soybean leaves and perilla leaves and
      lower levels in red peppers, corn grains and jujube grains. These results confirm
      that elemental concentrations in plant leaves are much higher than those in plant
      grain. Elevated levels of As, Sb and Bi were also found in stream sediments
      sampled in the vicinity of the mine and decreased with distance from the mine.
      Concentrations in stream water samples ranged from 0.8 to 19.1 microg As l(-1)
      and from 0.3 to 8.4 microg Bi l(-1); all the samples contained less than 1.0
      microg Sb l(-1). Because of very low particulate loading at the time of sampling,
      the metal contents in particulates were very low (< 8.2 microg As l(-1), < 0.22
      microg Sb l(-1) and 2.8 microg Bi l(-1). This may be mainly due to the low
      solubility of those elements under moderately acidic and oxidizing conditions of
      the mining area.

PMID- 12186295
TI  - Evaluation of the historical records of lead pollution in the annual growth rings
      and bark pockets of a 250-year-old Quercus crispula in Nikko, Japan.
AB  - The annual growth rings and bark pockets of a 250-year-old Japanese oak (Quercus
      crispula), collected from the Nikko National Park, Japan in 2000 AD, were
      analysed by ICP mass spectrometry. The annual rings, sampled in 5-year
      increments, recorded Pb concentrations from 0.01 to 0.1 mg kg(-1) and there was
      no significant change in concentration with time. In contrast, bark pocket
      samples dating from 1875 to the present showed a progressive increase in Pb
      concentration with time, from approximately 0.1 to 10 mg kg(-1). Shoots of
      epiphytic moss growing on the tree trunk contained 17 mg kg(-1) Pb. The bark
      pockets recorded historical increases in airborne Pb pollution accompanying the
      industrialisation of Japan, which was initiated by the opening of Japan's borders
      from 1854. This increase was not reflected by the annual rings. The 206Pb/207Pb
      isotope ratio of the bark pockets decreased from approximately 1.18 to 1.16 from
      1964 to the present, indicating changes in the sources of Pb pollution. The
      206Pb/207Pb isotope ratio of the moss shoots was similar to the current bark
      (1.16). The data showed bark pockets to be more effective than annual rings for
      recording historical change in airborne lead pollution.

PMID- 12186296
TI  - 3rd International Committee for Military Medicine course on International Law of
      Armed Conflict foreword.

PMID- 12186297
TI  - Caring for civilians during peace keeping missions: priorities and decisions.
AB  - Humanitarian assistance is increasingly being offered by the military in
      operations other than war. Balancing issues of resources, priorities, and
      security is important but complicated. Sometimes errors are made that are costly,
      either in terms of public relations, morale, or lives. Unfortunately, not enough
      education of physicians and other medical personnel is done prior to the mission,
      as to how to weigh these aspects. No absolute guidelines can be recommended, as
      each situation is different, but some examples and guidelines are presented.

PMID- 12186298
TI  - Military necessity versus the protection of the wounded and sick: a critical
      balance.
AB  - A realistic approach to humanitarian principles in the field of the Law of Armed
      Conflict should take into account "military necessity." Does military necessity
      also play a role in the medical field? The provisions regarding the treatment of
      the wounded and sick seem definite because they are at the core of International
      Humanitarian Law. The conduct of military medical personnel, the attention to be
      paid to the wounded and sick, as well as to medical equipment or facilities are
      provisions that derive from unyielding principles of care, respect, protection,
      and equality of treatment. To what extent may this analysis be considered as
      contrary to the common realism of LOAC? How far should medical personnel be
      requested to implement the Geneva standards in any circumstance? In fact, unless
      otherwise specified, military necessity can never lead to a reduction in these
      standards in the course of battle.

PMID- 12186299
TI  - History of the International Committee of Military Medicine.
AB  - Founded in 1921, after World War I had revealed the importance of a closer
      cooperation among the Armed Forces Medical Services worldwide, the International
      Committee of Military Medicine (ICMM) is today an international intergovernmental
      organization including over 100 States and recognized by the World Health
      Organization as specialized in medico-military matters. Besides maintaining and
      strengthening the bonds among all medical services of member states, the ICMM
      promotes medico-military scientific activities, participates in the development
      of the medico-military setting of humanitarian operations in peace time, and
      organizes various training courses in International Humanitarian Law and Law on
      Armed Conflict. This article gives an overview of the historical milestones of
      the ICMM from 1921 until today.

PMID- 12186300
TI  - Teaching the International Law of Armed Conflict to a wide military community.
AB  - The rules governing armed conflict are numerous and in many respects complex. In
      areas that are very complex, experts such as lawyers may be called in to assist,
      especially in the planning of military action. But the nature and tempo of
      warfare rarely allows a person in the field to enjoy such a luxury. Therefore,
      everyone involved in a military mission must have a basic working knowledge of
      their responsibilities according to the Law of Armed Conflict. The type and
      degree of knowledge will differ depending on the role and responsibility of the
      person. Accordingly, the knowledge base necessary for a foot soldier is often
      different from that which is required by a pilot. Even within a select group of
      combatants, the knowledge base required may differ from subgroup to subgroup. The
      knowledge required by a fighter pilot may be different, in some respects, from
      that of a pilot of an aircraft that provides transportation and logistical
      support. The fighter pilot must know what is an appropriate target; the
      transportation/logistical pilot may not need such knowledge.

PMID- 12186301
TI  - Medical ethics in peace and in the armed conflict.
AB  - Global medical ethics on the basis of the General Declaration of Human Rights by
      the United Nations is a key subject for the 21st century. World Health
      Organization's new definition of health includes "spiritual health," a term that
      has to be defined in international consensus despite different anthropologies,
      cultures, and religions. Old issues in medical ethics such as assisted suicide
      are still waiting for global consensus among the "pro-life" and "pro-choice"
      parties. So far The Netherlands and Belgium are the only countries where
      euthanasia has been legalized, whereas the U.S. Supreme Court has denied a right
      of medically assisted suicide. The respect of nature is also the basis for
      guidelines in new issues in medical ethics such as gene therapy and human
      cloning, which are controversially discussed. Military medical ethics should
      provide regulations for morally correct decisions in armed conflicts including
      the war against international terrorism and in peacekeeping missions. Triage of
      the wounded, distribution of medical aid, and critical incident stress debriefing
      for soldiers and their relatives are key issues.

PMID- 12186302
TI  - Experiences of the course. International Course on the Law of Armed Conflict.
AB  - This article reflects the experiences the commander and the chief medical officer
      of the course made. Creating an atmosphere of trust and mutual understanding
      helped to made participants at ease to discuss difficult issues openly. They
      learned that the most important problem for the participants was the issue of
      obeying orders, following medical ethical issues, and the simultaneous observance
      of Law of Armed Conflict. This gave rise to the greatest numbers of questions and
      concerns. Another hotly discussed issue was medical ethics in peace and war.
      Medical ethics is a very rapidly growing field of interest, which today is of
      concern to all of us, and this was reflected in the discussions of the
      participants. The last paragraph investigates what goals the course has achieved.

PMID- 12186303
TI  - Aims of the 3rd international course on the Law of Armed Conflict of the
      International Committee for Military Medicine.
AB  - The International Committee for Military Medicine (ICMM) decided at the 32nd
      Congress in Vienna in 1998 to give the Surgeon General of the Swiss Armed Forces
      the mandate to organize its international courses on the Law of Armed Conflict
      (LOAC). The Swiss Federal Government fully honored and endorsed its obligation to
      organize these important international courses. It is in the continuing tradition
      of Switzerland, as a small neutral state, to support humanitarian help and all
      efforts to prevent war. As decided by the head of the government on April 3,
      1998, the mandate of the LOAC Courses will be funded by the Swiss Confederation.

PMID- 12186304
TI  - International humanitarian law: an introduction.
AB  - War is the ultimate form of human relations. From a Christian and Jewish point of
      view, it negates the most important of the Ten Commandments: "Thou shallt not
      kill." Is it pure illusion to believe that war may be subject to legal rules? Was
      Cicero possibly right when he wrote inter arma silent leges (in war, the law is
      silent)? The horrors of wars in the last decades have made it clear that Cicero's
      approach would lead us to the ultimate catastrophe, simply because the
      destructive potential of modern weaponry is so overwhelming that we need rules
      governing warfare. This article intends to provide the reader with a brief
      introduction to the Law of Armed Conflict, its genesis, and its basic rules and
      principles with particular emphasis on rules regulating medical issues. Finally,
      we would like to show ways to implement Law of Armed Conflict in peacetime and
      during armed conflict. Where appropriate, reference is also made to the
      complementary body of human rights law and to standards of medical ethics.

PMID- 12186305
TI  - The effect of scopolamine in older rabbits tested in the 750 ms delay eyeblink
      classical conditioning procedure.
AB  - We investigated the effect of several doses of scopolamine in older rabbits that
      were trained for 20 days in the 750 ms delay eyeblink classical conditioning
      procedure. Our aim was to determine if the scopolamine-injected older rabbit
      would be a useful model for testing drugs for cognition enhancement in
      Alzheimer's disease (AD). A total of 39 rabbits with a mean age of 31 months
      received classical eyeblink conditioning with daily injections of 0.25, 0.75, or
      1.5 mg/kg scopolamine hydrobromide or sterile saline vehicle. Doses of 0.75 and
      1.5 mg/kg scopolamine significantly impaired acquisition, whereas acquisition was
      not significantly impaired with 0.25 mg/kg scopolamine. Results exhibit parallels
      in performance on delay eyeblink classical conditioning between scopolamine
      treated older rabbits and human patients diagnosed with AD.

PMID- 12186306
TI  - Compression and expansion of circadian rhythm in mice under long and short
      photoperiods.
AB  - Although the functional aspects of synchronization of the circadian pacemaker by
      environmental light have been extensively studied, few studies have provided
      systematic information about the temporal organization of behavior under light
      dark cycles with varying proportions of light and darkness. In the present study,
      the running-wheel activity profiles of mice were investigated under short,
      medium, and long photoperiods. The results clearly indicated that the temporal
      distribution of locomotor activity in mice is modulated by photoperiod. The
      activity profile was compressed under long photoperiods and expanded under short
      photoperiods. Although negative masking by light and alterations in the state of
      dark adaptation may have partially accounted for the phenomenon, the major
      mechanism seemed to be a compression and expansion of the circadian pacemaker's
      cycle, as expressed in the compression and expansion of the photic phase-response
      curve.

PMID- 12186307
TI  - Effects of stress on nonassociative learning processes in male and female rats.
AB  - In this study we assessed habituation and sensitization of the acoustic startle
      response (ASR) to discern whether intense, inescapable stress affects
      nonassociative learning differently in male and female rats. Rats were
      inescapably stressed 2 hours per day over 3 consecutive days. ASR magnitudes were
      measured at several times post-stress (1, 4, 8, and 15 days after cessation).
      Females generally showed greater ASR magnitudes (compared to males), but both
      sexes exhibited short and long-term habituation across the testing days. ASR
      magnitudes were only affected by stress in male subjects. The effect in males was
      an increase in short-term sensitization of the ASR on post-stress day-4. The
      results suggest that stressed males and females react differently to ASR testing,
      in that stress males appear to develop an exaggerated ASR response over repeated
      test sessions due to short-term sensitization. The source of the short-term
      sensitization is discussed with regards to possible stress-induced enhanced
      contextual learning during ASR testing on post-stress day-1.

PMID- 12186308
TI  - A study of the effects of restraint stress on colitis induced by dextran sulphate
      sodium in singly housed rats.
AB  - The inflammatory bowel diseases (Crohn's disease and ulcerative colitis) are
      multifactorial diseases. Clinical reports indicate that emotional stress may
      contribute to the onset, progression and remission of these diseases. Using an
      experimental animal model of ulcerative colitis, the effect of stress on the
      development of and recovery from symptoms was studied prospectively. Singly
      housed rats received 4 percent dextran sulphate sodium orally until fecal blood
      was detected, indicating the presence of colonic erosions. Tap water was then
      administered until there were no signs of fecal blood. Two hours of restraint
      stress were administered daily over four successive days, either prior to or
      after the induction of colitis. Latencies in days to symptom development and
      recovery were compared to an unstressed group. Daily measures of fluid-intake,
      body-weight, and hemoglobulin in feces were made. RESULTS: Rats exposed to
      restraint stress procedures prior to induction of colitis had shorter latencies
      to development of symptoms. There was no significant difference in latency to
      recovery. The amount of fluid-intake did not significantly differ between groups,
      nor did the groups differ in body-weight. CONCLUSION: There is an effect of
      stress on the latency to develop colitis induced by dextran sulphate sodium. This
      preliminary study suggests that the impact of stress may be one factor underlying
      the emergence of ulcerative colitis.

PMID- 12186309
TI  - QT & RR variability spots the earliest autonomic deregulation in diabetes. Fading
      of vagal sino-atrial drive but not of sympathetic ventricular responsiveness to
      life challenges.
AB  - 27 consecutive insulin-dependent diabetic patients (pts), under 50 years, with
      blood glucose controlled within normal limits and no significant or multiple
      cardiovascular/neurological complications in the lights of clinical tests, went
      through a protocol as follows: laiddown at relaxed rest for 10 min, then stood-up
      quietly for 7 min, and finally experienced a stress-interview for 10 min while
      supine. A thoracic ECG lead was digitized at I ms (Codas, Dataq Instr.), RR and
      QT intervals were software-detected, resampled at 500 ms, and Fourier-transformed
      over 3 min epochs to get auto-or cross-spectra. RR-by-QT mean square coherence
      detached the RR-independent fraction of QT low fequency (LF) spectral power,
      called idioventricular QT-LF. We detected autonomic impairment of three types
      (discriminant score = 92.31%), presumably differentiated upon the locus of
      lesion, using RR's basal variance and mean RR shortening when standing as
      follows: (I) RR shortening > 200 ms in 10 pts; (II) normal RR shortening but no
      RR variance in 4 pts; (III) stiff RR around 600 ms and no RR variance in 2 pts.
      The above pts have been excluded from further analysis. The remaining 11 pts with
      no such impairments (5M and 6F, 36.4 y +/- 4.4 SD, history of 6.0 y +/- 5.2) have
      been compared with 11 normal subjects in an age and gender-paired control group
      in two steps. Step 1: Preliminary MANOVA/ANOVA showed significant effects on the
      ensemble of spectral variables of every single factor (status: normal or patient
      group; intervention; gender) with no significant factor interactions. Significant
      effects of intervention or status on main RR spectral variables and on a few QT
      spectral variables were also documented. Step 2: Non-parametric tests showed that
      diabetics had (mildly to moderately) shorter mean RR, while their RR-LF was
      always significantly lower than those found in normals--a difference propagated
      to QT-LF but not to idioventricular QT-LF. In the intra-group there were similar
      responses to interventions except stress with respect to mean RR. Consistent
      reduction in RR-LF under moderate or no change in mean RR suggests vagal down-
      regulation that, judging by idioventricular QT-LF showing, goes perhaps before a
      similar process with sympathetic control of ventricles. This phase delay may
      introduce an early arrhythmic risk worth dealing with in secondary prevention.

PMID- 12186310
TI  - Dissociating basal forebrain and medial temporal amnesic syndromes: insights from
      classical conditioning.
AB  - In humans, anterograde amnesia can result from damage to the medial temporal (MT)
      lobes (including hippocampus), as well as to other brain areas such as basal
      forebrain. Results from animal classical conditioning studies suggest that there
      may be qualitative differences in the memory impairment following MT vs. basal
      forebrain damage. Specifically, delay eyeblink conditioning is spared after MT
      damage in animals and humans, but impaired in animals with basal forebrain
      damage. Recently, we have likewise shown delay eyeblink conditioning impairment
      in humans with amnesia following anterior communicating artery (ACoA) aneurysm
      rupture, which damages the basal forebrain. Another associative learning task, a
      computer-based concurrent visual discrimination, also appears to be spared in MT
      amnesia while ACoA amnesics are slower to learn the discriminations. Conversely,
      animal and computational models suggest that, even though MT amnesics may learn
      quickly, they may learn qualitatively differently from controls, and these
      differences may result in impaired transfer when familiar information is
      presented in novel combinations. Our initial data suggests such a two-phase
      learning and transfer task may provide a double dissociation between MT amnesics
      (spared initial learning but impaired transfer) and ACoA amnesics (slow initial
      learning but spared transfer). Together, these emerging data suggest that there
      are subtle but dissociable differences in the amnesic syndrome following damage
      to the MT lobes vs. basal forebrain, and that these differences may be most
      visible in non-declarative tasks such as eyeblink classical conditioning and
      simple associative learning.

PMID- 12186311
TI  - A national call to action: CDC's 2001 Urban and Rural Health Chartbook.
AB  - It remains to be seen if Congress will recognize the CDC report as a national
      call to action, or whether future CDC reports will simply record the ongoing
      health disparities of rural America. Regardless of the Congressional outcome in
      2002, the CDC report clearly succeeds in moving the national debate on rural
      concerns beyond the political rhetoric and into a data-driven debate.

PMID- 12186312
TI  - Assessment of a curricular component designed to introduce physical therapy
      students to rural practice issues.
AB  - A rural health curricular component was designed for students enrolled in a
      physical therapy program in Nevada to change student attitudes about rural
      practice and to encourage more physical therapy students to seek employment in
      rural areas postgraduation. Student attitudes and beliefs related to rural
      practice were investigated following participation in a rural health conference
      and a full-time rural clinical affiliation. Twelve students (N = 12)
      participated. All reported positive impressions of rural practice after
      participating in the rural clinical affiliation and nine (75%) were favorable
      toward seeking employment in a rural setting. Two (17%) accepted rural health
      positions following graduation. Clinical experience in a rural setting was found
      to have the greatest influence on student attitudes about rural practice.

PMID- 12186313
TI  - Unique advocacy opportunities for rural public health agencies.

PMID- 12186314
TI  - Developing, implementing, and evaluating a treatment protocol for rural substance
      abusers.
AB  - Substance abuse is a significant social and public health problem facing rural
      Americans. However, most treatment protocols have been developed in urban areas.
      This article describes the development, implementation, and evaluation of an
      innovative substance abuse treatment designed with the collaboration of rural
      professionals and consumers specifically for rural clients and delivered by rural
      clinicians. Results of the process evaluation of Structured Behavioral Outpatient
      Rural Therapy (SBORT) produced findings about the experiences of participating
      clients, clinicians, and program directors. Most clients perceived SBORT as a
      helpful learning process that used multiple treatment strategies and presented an
      alternative to 12-step programs. Clients also reported that treatment was
      stressful even when beneficial, and that clinician support was critical for
      remaining in treatment. Most clinicians found that SBORT challenged their "old"
      treatment frameworks, was demanding to learn and adopt, and that the training and
      supervision involved in the project implementation helped remedy rural isolation
      from the treatment community. Interestingly, agency approach to program
      implementation strongly influenced clinician responses to the innovation. Agency
      program directors' appraisals of SBORT included observations that the therapy was
      viable because of its rural-specific design and that most staff were able to
      adapt to the changes demanded by the manualized protocol. All three groups
      reported that they saw the emphasis and acceptance of motivation as an emergent
      process as important to the treatment. This project highlighted the challenge and
      importance of testing rural substance abuse treatment protocols in naturalistic
      settings.

PMID- 12186315
TI  - An outreach intervention for older rural African Americans.
AB  - This article describes the process, approaches, and selected outcomes of a rural
      care management outreach intervention for older African Americans in South
      Carolina. The model is a community-academic partnership between a federally
      qualified community health center, a rural health clinic, and the Medical
      University of South Carolina. Its aim is to improve access to and utilization of
      health care and social services to enhance the quality of life of older African
      Americans. This is being accomplished by using paid, trained outreach workers
      (called geriatric coordinators), who function as advocates in linking clients to
      needed health and social services through activities such as arranging
      transportation to health care, rescheduling missed medical appointments,
      providing health promotion, and making referrals to public benefits and indigent
      drug programs. Outcomes demonstrated that the use of geriatric coordinators as
      care managers is a feasible way of increasing quality of life for older African
      Americans. The most notable outcome showed that 54% of clients who were eligible
      but not receiving benefits prior to this intervention were signed on for programs
      such as Supplemental Security Income, Specified Low-Income Medicare Beneficiary
      (SLMB), Qualified Medicare Beneficiary (QMB), disability, railroad pensions, and
      Veterans Administration benefits. Health centers realized an increase in
      reimbursable services and new clients. Increased capacity for older adult
      services is being accomplished through geriatric-coordinator-directed
      collaborations with social service agencies and participation in community events
      and committees.

PMID- 12186316
TI  - The proximity of predominantly African American and Hispanic rural communities to
      physicians and hospital services.
AB  - This study assesses how local physician concentrations and distances to hospitals
      differ for rural communities of varying African American and Hispanic
      compositions. The authors used data at the town-area level (i.e., towns and their
      immediately surrounding minor civil divisions and census civil divisions) for 9
      Southern and 6 Western states, primarily for 1990. Data were from the US. Census,
      American Medical Association, and American Hospital Association. Analyses
      compared nonmetropolitan town-areas with low, medium, and high proportions of
      African Americans and Hispanics on their local physician-to-population ratios and
      distances to nearest hospitals offering each of four levels of services. The
      authors found that Western town-areas having over 50% Hispanic populations had
      lower physician densities than other Western town-areas that were predominantly
      non-Hispanic White (24.2 vs. 31.2 physicians per 100,000 population). In Southern
      town-areas, physician densities did not covary meaningfully with the proportion
      of African Americans. Distances to the nearest hospitals offering basic,
      intermediate, and tertiary subspecialty services were generally 25% to 35%
      farther for Southern town-areas composed of over 60% African Americans and for
      Western town-areas composed of over 50% Hispanics, compared to communities with
      more than 80% non-Hispanic White populations within each region. These
      relationships were not attributable to confounding by extraneous state factors,
      but in some cases were explained by community sociodemographic differences other
      than race. Thus, the authors learned that rural communities with populations that
      are predominantly Hispanic, but not those predominantly African American, face
      longer travel distances to physicians, and both groups face longer distances to
      some types of hospital services than rural communities with few minorities.

PMID- 12186317
TI  - Boundary maintenance as a barrier to mental health help-seeking for depression
      among the Old Order Amish.
AB  - This paper describes "boundary maintenance" as a barrier to help-seeking for
      depression within an Old Order Amish enclave. Observations and qualitative
      interview data were collected from 50 members of the Old Order Amish enclave and
      from the 8 mental health providers in their rural community. The Amish reported
      fairly high levels of depression, concomitantly high levels of reluctance to seek
      treatment for depression from mental health providers, and very low levels of
      service utilization. The functionality of boundary maintenance to group cohesion
      was discovered to be a significant barrier to help-seeking for depression from
      outside providers. Boundary maintenance was achieved through two social control
      mechanisms: religious-based stigmatization of depression and the construction of
      mental health providers as illegitimate help agents. Suggestions have been made
      to assist providers in achieving cultural competence among the Amish, in order to
      reduce the threat that the Amish perceive to their cultural boundaries.

PMID- 12186318
TI  - Unmet need among rural Medicaid beneficiaries in Minnesota.
AB  - Given the vulnerabilities of rural residents and the health care issues faced by
      the Medicaid population generally, the combined effects of being on Medicaid and
      living in a rural area raise important questions about access to health care
      services. This study looks at a key dimension of health care access: unmet
      needfor health care services. The study relies on data from a 1998 survey of
      rural Minnesota Medicaid beneficiaries. An overall response rate of 70% was
      obtained. For this study, the sample is limited to women who were on Medicaid for
      the full 12 months prior to the survey, resulting in 900 respondents. The study
      finds that the rural Medicaid beneficiaries face high levels of unmet need: more
      than 1 in 3 reported either delaying or not getting doctor, hospital, or
      specialist care that theyfelt they needed. Although the study lacks direct
      measures of the consequences of the high levels of unmet need, there is evidence
      that greater emergency room use is associated with unmet need. The survey data
      cannot necessarily be generalized to other rural areas, and like all surveys,
      this one is subject to nonresponse bias as well as potential biases because of
      respondent recall and self-assessment of medical needs. Nevertheless,
      thesefindings are suggestive of negative consequences of unmet need for both
      Medicaid beneficiaries and program costs.

PMID- 12186319
TI  - Food security and perceptions of health status: a preliminary study in rural
      Appalachia.
AB  - Food insecurity is estimated to affect about 10% of the United States population.
      Rural areas experience even higher rates and intensity of food security problems
      related to poverty, food access, and higher food costs. Reports of the
      relationship between household food security and health status, however, are
      limited. This report examines the relationship between household food security
      and measures of functional health status in a rural Appalachian sample. A
      comprehensive health status survey was completed by 1,006 individuals seen either
      in a clinical (n = 605) or nonclinical (n = 401) community setting. The survey
      included the USDA Food Security Core Module, the SF-36, and demographic and
      health care access questions. Household food insecurity was reported by 23% of
      respondents. Food insecure respondents reported significantly poorerfunctional
      status on all SF-36 scales compared tofood secure respondents (all p < 0.05).
      After adjusting for demographic and access variables in a multiple regression
      analysis, food insecurity remained a significant independent predictor of
      responses for each SF-36 scale. Generalizability of results are limited by the
      convenience sampling methods and geographic region in which the study was
      conducted. In this preliminary study, even minimal levels of food insecurity are
      related to self-reported levels of health status as measured by the SF-36
      spectrum. Health professionals must be able to identify individuals at risk for
      food insufficiency; policy makers must develop more effective programs for
      alleviating the basic causes of food insecurity.

PMID- 12186321
TI  - Pharmacy services in rural areas: is the problem geographic access or financial
      access?
AB  - Access to pharmacy services is an important rural health policy issue but limited
      research has been conducted on it. This article describes rural retail pharmacies
      in Minnesota, North Dakota, and South Dakota, including their organizational
      characteristics, staffing, services provided, and planned future changes;
      examines the availability of pharmacy services and pharmacy closures in rural
      areas of these three states; and briefly discusses policy issues that affect the
      delivery of pharmacy services in rural areas. Study data came from a phone survey
      of 537 rural pharmacies, an analysis of pharmacy licensure data, and phone
      interviews with clinic, public health, and social services staff in rural
      communities with potential pharmacy access problems. Using a standard of 20 miles
      to the nearest pharmacy, most rural residents of these three states currently
      have adequate geographic access to pharmacy services. However, rural pharmacists
      and clinic, public health, and social services staff rate financial access to
      pharmacy services for the elderly and the uninsured as a major problem. Key
      policy issues that will affect future access to pharmacy services in rural areas
      include pharmacy staffing and relief coverage; alternative methods of providing
      pharmacy services; thefinancial viability of rural pharmacies; and the potential
      impact of a Medicare prescription benefit on rural consumers and rural
      pharmacies.

PMID- 12186320
TI  - Variations in rural AIDS epidemiology and service delivery models in the United
      States.
AB  - This article reviews AIDS surveillance data and the rural health literature to
      summarize what is known about the rural AIDS epidemic, characteristics of rural
      environments that affect HIV service delivery, and approaches that rural areas
      are using to address the health and support service needs of HIV-positive
      residents. During 1999, nonmetropolitan (non-MSA) adult/adolescent AIDS rates
      were highest in the South (11 per 100,000) and Northeast (9 per 100,000). The
      South had the highest non-MSA proportion of adult/adolescent AIDS cases (12%),
      followed by the North Central region (9%), the West (4%), and the Northeast (3%).
      Variations in rural HIV/AIDS epidemiologic patterns and the demographic, socio
      economic, and cultural characteristics of rural environments are likely to
      require different levels of resource investment and different methods of
      organizing and delivering HIV services. Currently, many HIV-positive rural
      residents are traveling to metropolitan areas for medical care because of
      concerns about confidentiality or a lack of confidence in the HIV management
      capabilities of local physicians. Rural communities are attempting to address
      these problems by developing the HIV care capacity of existing clinics, building
      local networks of physicians with HIV management experience, and cultivating
      "shared care" arrangements with urban-based specialists.

PMID- 12186322
TI  - Managed care and developing countries: what are the equity implications?

PMID- 12186323
TI  - Injectables, incentives and disincentives: short-sighted population policies.

PMID- 12186324
TI  - Drug use among the urban poor in Kolkata: behaviour and environment correlates of
      low HIV infection.
AB  - BACKGROUND: HIV infection in injecting drug users (IDUs) has worked as a driving
      force for further spread of the virus in other population groups. Major
      metropolitan cities such as Mumbai, Kolkota, Chennai and Delhi have seen a
      diffusion of injecting drug use within the last decade. The prevalence of HIV
      infection among injectors ranges from 2% to 30%. Identifying effective
      interventional elements that have kept the prevalence of HIV low for the past 7
      years among IDUs of Kolkata is thus of public health importance. METHODS: A
      purposive sample of opioid/opiate users was studied. Primary and secondary data
      on drug users, law-enforcement environment, records at drug treatment centres,
      jail admission data related to the 'Narcotic Drug and Psychotropic Substance Act'
      and interventions in other risk groups were collected. Laboratory tests for HIV,
      hepatitis B surface antigen and syphilis were done on consenting IDUs (n=129) and
      non-IDUs (n=120). For univariate and multivariate analysis, IDUs were taken as
      cases and non-IDUs as controls. RESULT: Of the IDUs, 2% were positive for HIV. No
      non-IDU was HIV-positive. Significantly more non-IDUs (10% v. 4%, p=0.05) were
      positive for syphilis. Sharing injection equipment within the past 6 months was
      reported by 71% of IDUs; sharing partners were stable and ranged from 1 to 3.
      More IDUs compared to non-IDUs reported being in touch with intervention
      programmes. The police has been tolerant to needle-syringe exchange and oral
      sublingual buprenorphine substitution conducted in Kolkata. Unlike in the early
      1990s, non-IDUs did not switch to injecting during non-availability of brown
      sugar in the latter half of the 1990s and instead sought tratment. The
      availability of high quality heroin (>20%-50%) was low and the proportion of
      moderate quality heroin (>10%-20%) went up during these times due to increased
      police seizures. No intervention exists in jails despite the fact that a large
      number of drug users spend time in jail. CONCLUSION: Stable and few injection
      equipment-sharing partners of IDUs, launching of early targeted interventions
      among IDUs and sex workers in the city, police tolerance to harm reduction
      activities and preference of non-IDUs for detoxification during heroin draught
      periods have kept HIV prevalence at a low level among drug users of Kolkata for
      the past 7 years. immediate launching of interventions for drug users in jails
      seems necessary. Similar multi-pronged strategies with targeted and environmental
      intervention could work in other settings as well.

PMID- 12186326
TI  - Management strategies for duodenal ulcer in India in the helicobacter pylori era:
      an economic analysis.
AB  - BACKGROUND: Duodenal ulcer (DU) is widely prevalent in India. Eradication of
      Helicobacter pylori (H. pylori) is considered to be the most cost-effective first
      line therapy for DU in patients without a historyof use of non-steroidal anti
      inflammatory drugs. Western investigators recommend initial empirical anti-H.
      pylori therapy for such patients. However, in India similar recommendations are
      lacking due to the absence of appropriate clinical studies. METHODS: An economic
      analysis for the management of DU with particular attention to H. pylori
      infection was performed using a decision analysis model. Three treatment
      strategies for DU diagnosed at index endoscopy were evaluated: in strategy I,
      anti-secretory therapy alone was administered for 8 weeks; in strategy II, a
      urease test and histological examination for H. pylori was performed at the time
      of initial endoscopy and subsequent management was based on the result of these
      tests; and in strategy III, empirical triple therapy for possible H. pylori
      infection was considered. Costs per patient treated were the outcome variables
      compared among the three strategies. RESULTS: In the baseline analysis, the cost
      per patient managed with initial anti-secretory therapy alone was Rs 544, cost of
      performing the urease test and histological examination at the time of initial
      endoscopy and subsequent treatment was Rs 692, and strategy III of empirical
      triple therapy for H. pylori yielded a cost per patient of Rs 523. Sensitivity
      analysis with a wide range of clinical probabilities and cost estimates and a
      second-order Monte Carlo simulation supported the conclusions of the baseline
      analysis. CONCLUSION: Initial empirical triple therapy followed by anti-secretory
      therapy is the most cost-minimizing approach for the treatment of endoscopically
      documented DU in India.

PMID- 12186325
TI  - Community prevalence of sexually transmitted diseases and human immunodeficiency
      virus infection in Tamil Nadu, India: a probability proportional to size cluster
      survey.
AB  - BACKGROUND: Human immunodeficiency virus (HIV) infection and AIDS is threatening
      the survival of many nations. To evaluate ongoing interventional strategies and
      burden of illness estimates, valid data on the prevalence of HIV are required.
      Often, in the absence of community prevalence data, estimates are based on
      surrogate markers such as prevalence of HIV in antenatal clinics. Even though the
      antenatal prevalence of HIV is easier to measure and can be repeated for
      evaluation, it is important to establish the association between antenatal and
      community prevalence of sexually transmitted diseases (STDs) and HIV, so that the
      validity of the estimates can be verified. METHODS: A 'probability proportional
      to size' cluster survey was conducted in three randomly selected districts of
      Tamil Nadu in India. The basic unit of the survey was households from rural and
      urban clusters. Adults 15-45 years of age from the selected households were
      eligible for recruitment. Demographic, behavioural and laboratory data were
      collected. Clinical examination was done to identify STD syndromes and blood,
      urine, vaginal/urethral and endocervical swabs were taken for laboratory
      diagnosis of STDs from the subjects. Direct smear examination for Trichomonas
      vaginalis; serological tests for syphilis, hepatitis B, HIV, herpes simplex virus
      2, Chlamydia trachomatis; and culture of Neisseria gonorrhoeae and Haemophilus
      ducreyi were performed on the collected specimens. The data were analysed
      adjusting for cluster effect. RESULT: We selected and screened 1981 individuals
      (1157 women and 824 men) for STDs and HIV from 1114 households representing the
      25 million projected adult population of Tamil Nadu. The overall community
      prevalence of STDs including HIV and hepatitis B in Tamil Nadu was 14.6% (CI:
      14.1-15.1), and 8.3% (CI: 7.9-8.6) when HIV and hepatitis B were excluded.
      Community prevalence of HIV and hepatitis B infection was 1.8% (CI:1.7-1.9) and
      5.3% (CI: 5.1-5.5), respectively. The distribution of HIV involved both rural and
      urban regions of Tamil Nadu. On clinical examination, at least one STD syndrome
      was noted in 486 (24.5%) of the women subjects; vaginal discharge was the most
      common and found in 421 women (38.4%). CONCLUSION: The prevalence of STD and HIV
      in Tamil Nadu is higher than expected and has extended into the non-high risk
      population (generalized epidemic).

PMID- 12186328
TI  - Apoptosis: an ocular perspective.
AB  - Apoptosis is a programmed and controlled form of cell death, which is distinct
      from necrosis. It is a non-inflammatory process and plays an important role in
      numerous physiological and pathological events. It has an indispensable role in
      the development and homeostasis in tissues of all higher organisms. Apoptosis can
      be identified by various methods such as electron microscopy, agarose gel
      electrophoresis, deoxyribonucleic acid fragmentation analysis, Tdt-dUTP terminal
      nick end labelling (TUNEL) assay, flow cytometry, annexin V staining and enzyme
      assays. A number of genes have been identified which are involved in this
      process. Many approaches for the control of apoptosis are being developed from
      the understanding of its molecular mechanisms. These include pharmacological
      inhibition or overexpression of the involved genes, gene therapy by viral
      transduction of apoptotic inhibitors, inhibition of proteases, inhibition of
      intracellular rise in calcium concentration and inhibition by scavenging
      mediators of apoptosis such as reactive oxygen species. In the eye, apoptosis
      seems to play a role starting from embryogenesis to diseases of all its
      components. Modulation of apoptosis using different inducers and inhibitors could
      be of great importance.

PMID- 12186327
TI  - A serological study of human toxocariasis in north India.
AB  - BACKGROUND: Human toxocariasis owing to lodgement of the larvae of Toxocara canis
      in different organs can result in serious clinical syndromes such as visceral
      larva migrans or ocular larva migrans. Detection of an antibody response to
      Toxocara canis excretory-secretory (TES) antigen in serum samples is sensitive
      and specific for diagnosis and epidemiological surveys. To assess the extent of
      this problem in northern India, we tested the antibody response to the TES
      antigen by ELISA technique in subjects residing in a rural area near Chandigarh
      and in patients attending Nehru hospital, Chandigarh and clinically suspected to
      have toxocariasis. METHODS: Serum samples were collected from 94 randomly
      selected subjects, residents of Kheri village, Ambala district, Haryana; 30
      patients clinically suspected to have toxocariasis attending Nehru hospital,
      Chandigarh; 25 control patients and 15 normal healthy individuals. These were
      subjected to ELISA technique for detection of an antibody response to TES antigen
      usinga commercial kit (LMD Laboratories Inc. Ca. USA). All the samples were
      tested in duplicate and positive samples were tested by a different kit (Melotec
      Biotechnology, Spain). RESULTS: Of the 94 subjects residing in Kheri village and
      30 clinically suspected toxocariasis patients, 6 (6.4%) and 7 (23.3%),
      respectively, were seropositive for anti-Toxocara antibody response. A history of
      pica and/or contact with puppies could not be obtained from all the
      subjects/patients, hence the exact mode of transmission could not be ascertained.
      However, 3 (3.2%), 2 (2.13%) and 1 (1.06%) seropositive subjects in Kheri village
      were in the age groups of 1-10, 11-20 and 21-30 years, respectively, while 4
      (13.33%) and 3 (10%) seropositive patients who attended Nehru hospital,
      Chandigarh were in the age groups of 1-10 and 21-30 years, respectively. None of
      the control patients/healthy individuals were seropositive. CONCLUSION: A
      positive antibody response to TES antigen in 6.4% subjects residing in a rural
      area near Chandigarh and in 23.3% of patients clinically suspected to have
      toxocariasis indicates that human toxocariasis may be endemic in certain regions
      of northern India. A detailed epidemiological study is needed to determine the
      extent of this problem.

PMID- 12186329
TI  - Sentinel lymph node biopsy, axillary dissection and breast cancer: radiation
      oncologist's viewpoint.
AB  - Sentinel lymph node (SLN) identification and biopsy in breast cancer have been
      carried out successfully since the early 1990s. In early-stage breast cancer, the
      negative predictive value of a SLN biopsy is as high as 93%-100%. With a negative
      SLN, no axillary treatment would be required and the breast can be treated by
      tangential radiation fields. Currently, for a patient with a positive SLN,
      axillary dissection is recommended. Axillary irradiation can replace surgery with
      a low risk of recurrence (< 7%). The modern practice of radiotherapy, delivering
      a dose of 50 Gy to the axilla, has a low rate of late morbidity. Hence, it is now
      time to plan clinical trials comparing axillary irradiation with axillary
      dissection in SLN-positive, early-stage breast cancer. These approaches to the
      axilla, guided by the status of the SLN can reduce arm problems in women with
      breast cancer and improve their quality of life. Just as the treatment of the
      primary breast tumour has changed from Halstedian mastectomy to conservation
      surgery combined with breast irradiation, SLN biopsy may allow a move away from
      surgical axillary clearance and the associated morbidity in the future.

PMID- 12186330
TI  - High reproductive organ disease burden in rural African women.

PMID- 12186332
TI  - Training of postgraduates in anatomy.
AB  - It is recognized that training methods differ among the various medical colleges;
      however, trained specialists should be competent to discharge their duties
      independently in any part of the country. Therefore, to maintain uniform
      standards of education, there is a need to harmonize postgraduate training in
      anatomy. It is proposed that a structured training programme should be drawn up
      and monitored regularly at specified intervals, spelling out some clearly defined
      targets that need to be achieved. The ultimate goal of the postgraduate training
      programme should be to produce anatomists with sufficient knowledge and practical
      skills to undertake undergraduate teaching and evaluation in all branches of
      anatomy, as well as to pursue research independently.

PMID- 12186331
TI  - Early haemodynamic manipulation in severe sepsis and septic shock improves
      outcome.

PMID- 12186333
TI  - Sub-Saharan Africa's endless health problems.

PMID- 12186336
TI  - Epidemiology of acute poisoning.

PMID- 12186337
TI  - Emergency medicine: we need action.

PMID- 12186338
TI  - Contraceptive knowledge and practices among primigravidae at a tertiary care
      centre.

PMID- 12186339
TI  - Ethics of drug trials in India.

PMID- 12186340
TI  - Why do we overlook data from our own country?

PMID- 12186341
TI  - Tibolone, blood pressure and obesity.

PMID- 12186342
TI  - Specialists as a catalyst for excellence.

PMID- 12186344
TI  - Maxillary and mandibular bone reconstruction with hip grafts and implants using
      Frialit-2 implants.
AB  - Many types of osseointegrated implants that are very reliable and supported by
      scientific medium- and long-term studies are presently available. Often,
      unfavorable anatomic situations require bone augmentation procedures either prior
      to or at the same time as implant placement. Some of these procedures present
      limits. Using versatile implant systems is desirable in cases such as advanced
      osseointe-. gration, intraoral bone grafts or guided bone regeneration
      techniques, or major surgical reconstruction with bone grafts from the hip. The
      aim of this study was to evaluate the efficacy of the Frialit-2 implant in 29
      clinical cases of maxillary and mandibular reconstruction using different bone
      augmentation techniques, and to consider its success ratio through a 1- to 5-year
      follow-up.

PMID- 12186343
TI  - The effect of apically repositioned flap surgery on clinical parameters and the
      composition of the subgingival microbiota: 12-month data.
AB  - The purpose of this investigation was to examine the clinical and microbiologic
      effects of apically repositioned flap surgery. Eighteen patients with chronic
      periodontitis received initial preparation (IP) including scaling and root
      planing, followed at 3 months by apically repositioned flap surgery at sites with
      pocket depth > 4 mm. Subjects were monitored clinically and microbiologically at
      baseline, 3 months after IP, and at 3, 6, 9, and 12 months postsurgery. Clinical
      assessments of plaque accumulation, gingival redness, suppuration, bleeding on
      probing, pocket depth, and attachment level were made at six sites per tooth.
      Subgingival plaque samples were taken from the mesial aspect of each tooth, and
      the presence and levels of 40 subgingival taxa were determined using checkerboard
      DNA-DNA hybridization. Significant reductions were seen in mean pocket depth and
      percentage of sites exhibiting gingival redness and bleeding on probing in both
      sites that received IP only and in sites receiving IP followed by surgery. Mean
      attachment level increased significantly for both sets of sites, but the increase
      was greater at the surgically treated sites. The total DNA probe counts were
      significantly reduced at sites in both treatment groups. At surgically treated
      sites, 19 of 40 taxa were significantly reduced posttherapy At sites receiving IP
      only, 16 species were significantly reduced over time. While there were some
      reductions in mean counts after IP in this site group, the major reductions
      occurred after the surgical phase in these patients, even though these particular
      sites did not receive surgical therapy. The reduction in pocket depth by surgical
      means and the associated decrease in reservoirs of periodontal pathogens may be
      important in achieving sustained periodontal stability.

PMID- 12186345
TI  - Osteoporosis: the effect on mandibular bone resorption and therapeutic
      possibilities by means of implant prostheses.
AB  - In recent years, considerable attention has been given to the interrelationship
      between the outbreak of a systemic process of reduction in the bone mass and the
      possibility of a significant resorption of the alveolar bone. The degree of
      alveolar bone loss increases with age, and this may be related, at least in part,
      to the systemic conditions that also encourage the development of osteoporosis.
      Although numerous studies have documented the possible role of osteoporosis as a
      deteriorating factor in both tooth loss and mandibular bone resorption, this
      article underlines how the morphostructural evolution of the edentulous mandible
      is primarily correlated to mechanical factors as a result of modifications to its
      function. We will also take into consideration the therapeutic advantages
      provided by prosthetic rehabilitation on osseointegrated implants, in terms of
      reinstatement of the loading conditions through patterns of propagation of
      mechanical forces that are similar to physiologic ones.

PMID- 12186346
TI  - Tooth structure removal associated with various preparation designs for posterior
      teeth.
AB  - The amount of tooth structure removed for various innovative and conventional
      preparation designs for fixed prosthodontics was quantified. Four Typodont resin
      teeth representing maxillary and mandibular premolars and molars were prepared in
      various abutment designs: adhesive, box (A2); adhesive, wing and groove (A3);
      mesioocclusal or distoocclusal inlay; mesio-occlusodistal inlay (13); mesio
      occlusodistal onlay; partial crown; half crown (only molars); complete crown, 0.8
      mm circumferential tapered chamfer (F1); complete crown, 1.0-mm circumferential
      rounded shoulder; and complete crown, 1.4-mm axial reduction facial shoulder, 0.7
      mm lingual chamfer (F3). After tooth preparation (10 per group), the root was
      separated from the anatomic crown at the cementoenamel junction. Removal of tooth
      structure was measured by gravimetric analysis in a high-precision balance.
      Preparations A3 and F3 were assigned as abutments for metal-supported
      restorations, whereas all other preparations were used for all-ceramic
      restorations. When the mean structure removal of all teeth tested was compared,
      the adhesive and inlay abutments were the least invasive preparation designs,
      ranging from approximately 5.5% (A2) to 27.2% (13) tooth structure removal.
      Complete crowns required the most invasive preparations, ranging from 67.5% (F1)
      to 75.6% (F3) tooth structure removal. The tooth structure removal required for
      F3 retainers was almost 14 times greater than for an A2 preparation. Tooth
      structure removal was also influenced by the morphology of the tooth. The first
      comprehensive tooth preparation design classification system was introduced. The
      measurement system used in this study provides an accurate method of quantifying
      tooth structure removal for fixed prosthodontic preparations. The innovative
      preparation designs studied conserved significant amounts of tooth structure,
      yielding a better prognosis for the restored tooth.

PMID- 12186347
TI  - Vertical distraction osteogenesis of fibular free flap in mandibular prosthetic
      rehabilitation: a case report.
AB  - A 17-year-old boy underwent three cycles of chemotherapy and a subsequent
      mandibular resection for a Ewing's sarcoma of the left body and ramus. The
      mandible was immediately reconstructed with a microvascular osteomuscular fibular
      flap. One year after the mandibular reconstruction, distraction osteogenesis of
      the anterior portion of the fibula was performed using a Martin distractor
      according to the Hoffmeister technique. Bone lengthening was achieved at a rate
      of 1 mm/day by turning the device twice each day for 12 days. Subsequently, we
      waited for 70 days for bone consolidation to occur. After 6 additional weeks,
      five Maestro implants were placed into the distracted fibula. Bone specimens were
      retrieved with a trephine bur during implant placement. Mature bone was present
      after 70 days and after 6 months. The bone height increase was 12 mm.

PMID- 12186348
TI  - Clinical evaluation of an enamel matrix protein derivative (Emdogain) combined
      with a bovine-derived xenograft (Bio-Oss) for the treatment of intrabony
      periodontal defects in humans.
AB  - The purpose of the present study was to compare the treatment of deep intrabony
      defects with a combination of an enamel matrix protein derivative (EMD; Emdogain)
      and a bovine-derived xenograft (BDX; Bio-Oss) to BDX alone. Twenty-four healthy
      patients, each of whom displayed one intrabony defect, were randomly treated with
      a combination of EMD + BDX (test) or with BDX alone (control). Soft tissue
      measurements were made at baseline and 1 year following the therapy No
      differences in any of the investigated parameters were observed at baseline
      between the two groups. No adverse healing response was observed in any of the
      patients. At 1 year after therapy, the sites treated with EMD + BDX showed a
      reduction in probing pocket depth (PPD) from 10.0 +/- 1.5 mm to 4.3 +/- 1.4 mm
      and a change in clinical attachment level (CAL) from 10.9 +/- 2.0 mm to 6.2 +/-
      1.9 mm (P <.0001). In the group treated with BDX, the PPD was reduced from 9.7 +/
      2.4 mm to 3.2 +/- 0.7 mm and the CAL changed from 10.1 +/- 2.3 mm to 5.2 +/- 1.2
      mm (P <.0001). Hard tissue fill was observed radiographically in all defects.
      Both treatments resulted in significant improvements of PPD and CAL. However, no
      statistically significant differences in any of the investigated parameters were
      observed between the test and control groups. Both therapies led to significant
      improvements of the investigated clinical parameters.

PMID- 12186350
TI  - Two uncommon uses of Bio-Oss for GTR and ridge augmentation following
      extractions: two case reports.
AB  - Bio-Oss is natural bovine bone mineral, which has the property of bone
      conduction. It is recommended to be used in two- or three-walled bony defects
      with an ample supply of pleuripotential cells. Two cases are reported. The first
      was an intentional replantation, because of previous trauma, of a hopeless tooth
      affected with severe periodontitis. The tooth was replanted after complete
      elimination of granulation tissue. Bio-Oss, together with a guided tissue
      regeneration (GTR) membrane, was used to enhance periodontal regeneration. After
      2 years of follow-up, the replanted tooth was quite stable. In the second case,
      Bio-Oss, together with bone taken from the retromolar area, was used in a sinus
      lift grafting procedure after the removal of two supernumerary teeth from the
      floor of the maxillary sinus. Four months after grafting, an orthodontic
      treatment was applied to move the two adjacent teeth through the grafted site and
      align them in the proper position. The clinical results of the two cases were
      satisfactory.

PMID- 12186349
TI  - Immunologic effects of emdogain in humans: one-year results.
AB  - Tissue regeneration after therapeutic manipulations is essential in
      periodontology, oral surgery, and trauma of the periodontal tissues. Local
      inflammation because of poor oral hygiene also plays a crucial role in the above
      situations. Local inflammatory reaction, accompanied by the local production of
      cytokines, profoundly influences bone turnover and regeneration. Several products
      of low immunogenicity for augmenting tissue regeneration have been recently
      proposed as boosters of soft and mineralized tissue regeneration. Among them,
      Emdogain, an amelogenin derivative of porcine origin, has recently been
      introduced. Clinical results indicate that this product might be a good additive,
      producing fast tissue regeneration with no apparent clinical side effects. In
      contrast, very little is known about its in vivo immunologic effects. A previous
      study showed that Emdogain does not modify the cellular or humoral immune
      response in vitro. In the present work, performed in 10 patients, only a slight,
      nonsignificant activation of the immune system occurred during the first year
      following Emdogain application. Neither cellular immunity nor humoral immune
      response was significantly modified. In addition, the in vitro response of the
      patients' lymphocytes to Emdogain was assayed 2 and 12 months postoperative. We
      did not find any significant specific lymphocyte transformation in the presence
      of Emdogain, although lymphocytes could be stimulated by nonselective mitogens.
      These results indicate the immunologic safety of the agent in vivo, at least
      after 1 year.

PMID- 12186351
TI  - Fate of the HA coating of loaded implants in the augmented sinus floor: a human
      case study of retrieved implants.
AB  - A histomorphometric study was performed on six retrieved loaded hydroxyapatite
      (HA)-coated titanium implants. The implants had been clinically functioning in a
      50-year-old patient. She originally presented a severely atrophic maxilla that
      was reconstructed by sinus floor augmentation using autogenous bone from the
      iliac crest. In spite of good clinical function, because of psychiatric problems,
      all implants, including some bordering bone, were removed using a trephine bur.
      Thin ground sections were prepared for histology and used for histomorphometry.
      The aim of this study was to observe the condition of the calcium phosphate
      coating after 2.5 years of functional loading, the nature of the bone-to-implant
      interface, as well as the density of the bone graft around the implants. Intimate
      and abundant bone-to-implant contact was observed, ranging from 90.4% to 99.8%
      along the implant surface. Active bone remodeling occurred within all threads, as
      demonstrated by secondary osteons close to the implant surface. The thickness of
      the calcium phosphate coating varied from 51 to 88 pm for the loaded retrieved
      implants, versus 53 to 89 microm for the nonused control implant. All implants
      showed bone contact including the first thread and up to the smooth titanium
      neck. Both the nature and thickness of the coating had hardly changed after 2.5
      years of loading. The HA-coated implants used achieved excellent osseointegration
      and must be considered clinically safe and effective in maxillary grafted bone.

PMID- 12186352
TI  - A cognitive model of insomnia.
AB  - Insomnia is one of the most prevalent psychological disorders, causing sufferers
      severe distress as well as social, interpersonal, and occupational impairment.
      Drawing on well-validated cognitive models of the anxiety disorders as well as on
      theoretical and empirical work highlighting the contribution of cognitive
      processes to insomnia, this paper presents a new cognitive model of the
      maintenance of insomnia. It is suggested that individuals who suffer from
      insomnia tend to be overly worried about their sleep and about the daytime
      consequences of not getting enough sleep. This excessive negatively toned
      cognitive activity triggers both autonomic arousal and emotional distress. It is
      proposed that this anxious state triggers selective attention towards and
      monitoring of internal and external sleep-related threat cues. Together, the
      anxious state and the attentional processes triggered by it tricks the individual
      into overestimating the extent of the perceived deficit in sleep and daytime
      performance. It is suggested that the excessive negatively toned cognitive
      activity will be fuelled if a sleep-related threat is detected or a deficit
      perceived. Counterproductive safety behaviours (including thought control,
      imagery control, emotional inhibition, and difficulty problem solving) and
      erroneous beliefs about sleep and the benefits of worry are highlighted as
      exacerbating factors. The unfortunate consequence of this sequence of events is
      that the excessive and escalating anxiety may culminate in a real deficit in
      sleep and daytime functioning. The literature providing preliminary support for
      the model is reviewed and the clinical implications and limitations discussed.

PMID- 12186353
TI  - Cognitive-behavioral treatment of high anger drivers.
AB  - Relaxation and cognitive-relaxation interventions were compared to a no treatment
      control in the treatment of high anger drivers. The cognitive portion of the
      cognitive-relaxation condition adapted the style of Beck's cognitive therapy,
      particularly use of Socratic questions and behavioral experiments and tryouts, to
      driving anger reduction. Both interventions lowered indices of driving anger and
      hostile and aggressive forms of expressing driving anger and increased
      adaptive/constructive ways of expressing driving anger. The cognitive-relaxation
      intervention also lowered the frequency of risky behavior. Both interventions
      lowered trait anger as well. Limitations and implications for treatment and
      research were discussed.

PMID- 12186354
TI  - An experimental test of stimulus estimation theory: danger and safety with snake
      phobic stimuli.
AB  - The stimulus estimation model (Taylor & Rachman, 1994) asserts that fear
      overprediction stems from: (a) overprediction of the danger elements of a phobic
      stimulus, and (b) underprediction of existing safety resources. Using a 2x2
      factorial design, with danger (high vs low) and safety (high vs low) as between
      subjects variables, an experimental test of the model was conducted with 25 snake
      fearful participants per condition. The four experimental conditions were matched
      on initial levels of snake fearfulness, as assessed by the Snake Questionnaire
      (SNAQ). For the 51 participants who demonstrated overprediction of fear, high
      danger led to reliably more fear overprediction than low danger; and low safety
      led to reliably more fear overprediction than high safety. The interaction
      between danger and safety was not statistically significant. The results offer
      the first convincing experimental support for the stimulus estimation model of
      fear overprediction.

PMID- 12186355
TI  - Thought suppression, intelligence, and working memory capacity.
AB  - The importance of individual differences in intelligence and working memory
      capacity in predicting the ability to intentionally suppress thoughts was
      investigated. Sixty participants completed a thought suppression task, and
      measures of working memory capacity (OSPAN), fluid intelligence (Raven's
      Matrices), and crystallised intelligence (the National Adult Reading Test). As
      predicted, the results indicated that more effective thought suppression was
      independently related to higher working memory capacity and greater fluid
      intelligence, but was unrelated to crystallised intelligence. The findings have
      theoretical implications for understanding the mechanisms underlying a failure to
      inhibit unwanted intrusions and clinical implications for disorders involving
      high levels of intrusive thoughts and memories.

PMID- 12186356
TI  - The Intolerance of Uncertainty Scale: psychometric properties of the English
      version.
AB  - Research is now suggesting that intolerance of uncertainty may be very important
      in understanding worry and may play a key role in the etiology and maintenance of
      worry. The present study attempted to further our understanding of intolerance of
      uncertainty by examining the psychometric properties of the English version of
      the Intolerance of Uncertainty Scale (IUS), which has already been validated in
      French. Factor analysis indicated that the IUS has a four-factor structure that
      represents the idea that uncertainty is stressful and upsetting, uncertainty
      leads to the inability to act, uncertain events are negative and should be
      avoided, and being uncertain is unfair. The IUS has excellent internal
      consistency, good test-retest reliability over a five-week period, and convergent
      and divergent validity when assessed with symptom measures of worry, depression,
      and anxiety. Overall, this study suggests that the IUS is a sound measure of
      intolerance of uncertainty and supports the idea that intolerance of uncertainty
      is an important construct involved in worry.

PMID- 12186357
TI  - Differentiating anxious, aggressive, and socially competent preschool children:
      validation of the Social Competence and Behavior Evaluation-30 (parent version).
AB  - The present study examined the factor structure, internal consistency, and
      construct validity of the parent version of the Social Competence and Behavior
      Evaluation-30 for preschoolers (SCBE-30; LaFreniere, P. J. (1990). Social
      competence and behavior evaluation-30. Unpublished measure.), an adaptation of
      the validated teacher version of the same measure (LaFreniere & Dumas, Psychol.
      Asses. 8 (1996) 369). The parent version of the SCBE-30 is a 30-item Likert
      rating scale questionnaire designed to assess patterns of anxiety/withdrawal,
      anger/aggression, and social competence. Principal components analysis was used
      to identify the factor structure of the parent version of the SCBE-30 (N = 218
      preschool children). To assess construct validity, a compliance task was utilized
      to determine whether children identified as high on anxiety/withdrawal,
      anger/aggression, or social competence with the parent version of the SCBE-30 (n
      = 20 for each group) could be distinguished behaviorally on several observational
      variables. Principal components analysis identified three factors accounting for
      44% of the variance. Ten items positively loaded onto each factor and matched
      conceptual expectations. A between-subjects MANOVA demonstrated significant group
      differences in observed child behaviors including compliance, noncompliance,
      subtypes of noncompliance, and aversive behavior. Results of the current study
      suggested that the parent version of the SCBE-30 demonstrated both internal
      consistency and construct validity, and findings paralleled many of the results
      from LaFreniere and Dumas' validation of the teacher version of the SCBE-30.

PMID- 12186358
TI  - The psychometric properties of the Interpersonal Sensitivity Measure in social
      anxiety disorder.
AB  - The Interpersonal Sensitivity Measure (IPSM) was developed to assess
      hypersensitivity to interpersonal rejection, a suggested trait of depression
      prone personality (Aust NZ J Psychiatry 23 (1989) 341). Although studies of the
      IPSM and interpersonal rejection sensitivity have primarily been conducted in
      depressed populations, it is important to investigate interpersonal rejection
      sensitivity as a relevant construct in the assessment of social anxiety. This
      study examined the psychometric properties of the IPSM in treatment-seeking
      individuals with social anxiety disorder. The results of this investigation
      support the convergent and divergent validity and internal consistency of the
      IPSM in socially anxious individuals. An exploratory factor analysis of the scale
      was also conducted after the original factor and subscale structure was shown to
      be a poor fit for the present data. Three factors emerged (Interpersonal Worry
      and Dependency, Low Self-Esteem, and Unassertive Interpersonal Behavior), and 29
      items were retained. Because they demonstrated negative factor loadings on Factor
      2, it is suggested that the scoring for four items of the original IPSM be
      reversed. In summary, the revised IPSM assesses three aspects of interpersonal
      rejection sensitivity and appears to be a valid and reliable instrument for its
      assessment in social anxiety disorder.

PMID- 12186359
TI  - Confounding and bias in epidemiological investigations.

PMID- 12186360
TI  - Pediatric oncology at Hospital Infantil de Mexico: fifty-five years of
      accomplishment.
AB  - The Department of Oncology at Hospital Infantil de Mexico Federico Gomez (HIMFG)
      was the first unit in our country, and one of the first in Latin America, to
      specialize in the management of children with cancer. The HIMFG is part of the
      National Institutes of Health of Mexico, and is a reference hospital with
      research, educative, and tertiary care medical function. To date, the HIMFG and
      the Instituto Nacional de Pediatria are the principal medical centers in which
      children with cancer receive comprehensive care.

PMID- 12186361
TI  - Type I Gaucher disease in children with and without enzyme therapy.
AB  - This retrospective study describes the course of 56 children with non
      neuronopathic Gaucher disease who presented at <16 years and were followed at 6-
      to 12-month intervals for 3-9 years. Massive splenomegaly and height retardation
      marked those who required treatment. Enzyme replacement significantly increased
      hemoglobin levels; platelet counts were divergent at presentation and follow-up,
      regardless of therapy. Among treated patients there was a significant reduction
      in liver and spleen index volumes, and a significant increase in height z-scores.
      None of the children required splenectomy or developed lung involvement. Many
      patients diagnosed due to large-scale screening were very mildly affected and
      remain untreated.

PMID- 12186362
TI  - The synergistic effect of thrombopoietin in erythropoiesis with erythropoietin
      and/or IL-3 and myelopoiesis with G-CSF or IL-3 from umbilical cord blood cells
      of premature neonates.
AB  - The authors sought to determine whether recombinant human thrombopoietin (TPO)
      acts synergistically with other cytokine(s) on burst-forming unit-erythroid (BFU
      E)-derived and colony-forming unit-granulocyte/macrophage (CFU-GM)-derived colony
      formations from cord blood of premature neonates. Cord blood nonadherent
      mononuclear cells (MNC) from normal premature neonates were cultured in a
      methylcellulose system. When cultured with 1 x 10(4) MNC/mL, erythropoietin (EPO)
      2 U/mL, interleukin-3 (IL-3) 50 ng/mL, and/or TPO 100 ng/mL, the addition of TPO
      to EPO gave rise to more BFU-E-derived colonies (p = .000). The addition of TPO
      to EPO + IL-3 gave rise to more BFU-E-derived colonies (p = .002) also. TPO
      synergizes erythropoiesis from cord blood of premature neonates. Likewise, the
      addition of TPO to G-CSF gave rise to more CFU-GM-derived colonies (p = .000)
      also. TPO synergizes myelopoiesis from cord blood of premature neonates. Thus,
      TPO has synergistic effects on both erythropoiesis and myelopoiesis from cord
      blood of premature neonates.

PMID- 12186363
TI  - Anti-D exerts a very early response in childhood acute idiopathic
      thrombocytopenic purpura.
AB  - Acute idiopathic (immune) thrombocytopenic purpura (ITP) in the pediatric
      population is a disease in which autoimmune features are mainly self-limited,
      with a reported mortality of 0.1-0.5%. Major treatment requires intravenous
      gammaglobulins (i.v. IgG) and corticosteroids. Recently a new globulin, anti-D,
      has been introduced. The authors have treated 25 children suffering from acute
      idiopathic thrombocytopenic purpura, with an i.v. anti-D dose of 75 microg/kg as
      the first treatment. Eligibility criteria included a platelet count < 15,000 and
      Rh+. Post-treatment response was 76% > 20,000 platelets at 6-10 h and 80% >
      50,000 platelets at 48 h; three patients developed chronic idiopathic
      thrombocytopenic purpura. There were 5/25 patients who did not respond to the
      initial dose and received i.v. IgG and corticosteroids, 2/5 with a positive
      response (platelets > 20,000). Side effects consisted of chills (9/25), fever >
      38 degrees C (6/25), headache and vomiting (1/25), hemolysis (20/25) from 0.9-6.9
      g%, and decrease in hemoglobin levels. One patient needed a blood transfusion
      after his Hbg decreased from 12.4 to 5.5 g%. The results indicate that anti-D is
      an effective treatment in acute ITP, but with side effects. Administration of
      steroids and antipyretics prior to anti-D treatment may prevent the side effects.

PMID- 12186364
TI  - A novel missense mutation in the DKC1 gene in a Japanese family with X-linked
      dyskeratosis congenita.
AB  - The authors report 2 male patients with dyskeratosis congenita (DC) in a Japanese
      kindred. Sequencing of the complementary DNA of the dyskerin gene (DKC1) revealed
      a T-to-C transition at nucleotide 1285 in exon 12 that resulted in a novel
      missense mutation L398P. Despite harboring the same mutation in the DKC1 gene,
      one patient had significantly milder hematological symptoms than the other,
      indicating that there may be other factors that determine the severity of DC.

PMID- 12186365
TI  - Rare tumors of the lung in children.
AB  - The authors report rare and different types of lung tumors in 4 children. The
      first case is an 8-year-old boy with mucoepidermoid carcinoma, the second case is
      a 9-year-old girl with neuroendocrine carcinoma, the third is a 14-year-old girl
      with fetal lung adenocarcinoma (FLAC), and the last is a 16-year-old girl with
      bronchioloalveolar carcinoma. Among these tumors, FLAC has not been reported in
      children so far. Each tumor type displayed a different prognosis in the follow-up
      period. In the differential diagnosis of primary lung tumors, carcinoid tumor,
      bronchogenic carcinoma, and pulmonary blastoma are frequently encountered, but
      these rare tumor types should be borne in mind.

PMID- 12186366
TI  - The association of leukocyte adhesion defect type I and persistent
      hyperinsulinemic hypoglycemia of infancy in a Saudi Arabian family.
AB  - The authors describe 2 female sibling infants diagnosed with leukocyte adhesion
      defects CD11 and CD18. Both had successful bone marrow transplants from identical
      siblings. One of the patients was found to have persistent hypoglycemia of
      infancy. The association of these two rare conditions has not been reported
      previously.

PMID- 12186367
TI  - Virus-associated immune thrombocytopenic purpura in childhood.
AB  - Idiopathic thrombocytopenic purpura (ITP) in children is usually a self-limiting
      disorder. It may follow a viral infection or immunization and is caused by an
      inappropriate response of the immune system. Many viruses, such as human
      immunodeficiency virus, cytomegalovirus (CMV), Epstein-Barr virus (EBV),
      varicella, rubeola, mumps, and parvovirus, have been implicated in childhood ITP.
      This study is a retrospective chart review of pediatric patients diagnosed with
      virus-associated ITP at the Hacettepe University, Ihsan Dogramaci Children's
      Hospital from 1997 to end of 2000. In viral serological studies, the EBV, CMV,
      and rubella antibodies were investigated for all patients at diagnosis (ELlSA).
      The proportion of children whose ITP was associated with documented acute viral
      infection was 13.3% in this group. In the present study, clinical manifestations
      and laboratory data of virus-associated or not associated groups are similar
      except age. Median age of the virus-associated group is younger than that of the
      other, but it is not statistically significant.

PMID- 12186368
TI  - Successful transplantation of haploidentical CD34+ selected bone marrow cells for
      an infantile case of severe combined immunodeficiency with aspergillus pneumonia.
AB  - A 5-month-old boy with X-linked severe combined immunodeficiency (SCID) and
      aspergillus pneumonia was successfully transplanted. Before and during
      transplantation, the patient received O2 administration, systemic amphotericin B,
      and itraconazole. The transplant was performed with a conditioning regimen of
      busulfan/cyclophosphamide and 2.9 x 10(6)/kg of CD34+ selected bone marrow cells
      from his HLA haploidentical mother. Acute grade II graft-versus-host disease
      (GvHD) was well controlled. Neutrophil counts reached >0.5 x 10(9)/L by day 15
      and platelet counts reached > 50 x 10(9)/L by day 48. The T-cell subset (counts)
      in peripheral blood increased to 42.2% (0.31 x 10(9)/L) by day 46. The pneumonia
      improved by day 54. The patient has been doing well with limited chronic GvHD of
      the gut with a follow-up of longer than 40 months after BMT. Conquest of
      aspergillus pneumonia in SCID infants could be achieved by CD34+ bone marrow cell
      transplantation together with appropriate anti-fungal treatment.

PMID- 12186369
TI  - Infantile fibrosarcoma associated with urticaria pigmentosa.
AB  - The authors report the case of an infant with urticaria pigmentosa who developed
      infantile fibrosarcoma. The tumor was successfully resected but the skin lesions
      have persisted. This is the first report of a fibrosarcoma in association with
      urticaria pigmentosa. A brief review is presented of the available medical
      literature on associations of solid tumors with mastocytosis.

PMID- 12186371
TI  - Evaluation of HER-2/NEU protein expression in breast cancer by
      immunohistochemistry: an interlaboratory study assessing the reproducibility of
      HER-2/NEU testing.
AB  - This study investigated the degree of interlaboratory agreement when HER-2/neu
      was evaluated by immunohistochemistry (IHC) on archival primary breast cancer
      samples. IHC for HER-2/neu was performed on the same archival tissue sections
      from 394 invasive primary breast cancers in two different laboratories. Both
      laboratories used the primary antibody NCL-CB11; however, different methods of
      immunostaining (antigen retrieval procedure and manual processing or no antigen
      retrieval and autostainer processing) as well as different scoring systems were
      used. Fluorescence in situ hybridization (FISH), considered as the correlation
      method for HER-2/neu status determination, was performed using the PathVysion kit
      and compared to the IHC results. Forty-eight of 394 analyzed tumors (12.2%) were
      scored as HER-2/neu positive in one laboratory, and 109 (27.7%) in the other
      laboratory where antigen retrieval was performed. Complete concordance in
      categorization of HER-2/neu status between the two laboratories was achieved in
      333 of 394 cases (84.5%). FISH performed in 248 formalin-fixed samples revealed
      HER-2/neu gene amplification in 55/248 (22.2%). Concordance of FISH and IHC was
      found in 211/248 cases (85.1%) and 220/248 cases (88.7%) when the CB11 antibody
      was used without and with antigen retrieval, respectively. Both IHC methods
      generated similar rates of false results, but with different positive predictive
      values. Our data demonstrate that HER-2/neu evaluation by IHC is not a
      reproducible technique if there is no standardization of the procedure.

PMID- 12186370
TI  - Indium-111-octreotide scintigraphy, intraoperative gamma-detector localisation
      and somatostatin receptor expression in primary human breast cancer.
AB  - 12 women with primary breast cancer underwent somatostatin receptor scintigraphy
      (SRS) with 111In-DTPA-D-Phe1-octreotide. The tumour sizes varied between 2 and 5
      cm and were all, except one, palpable at clinical examination. Tumour biopsies
      were taken with additional sampling from normal breast tissue, fat, muscle,
      axillary lymph nodes and peripheral blood. Ratios between the 111In activity
      concentration in the tissue biopsies (Ti) and in peripheral blood (B) as well as
      in normal breast tissue (Br) were calculated. In 8/12 patients the scintillation
      detector was used intraoperatively for radioactivity measurements of the biopsies
      in situ and ex vivo. The sstr-subtype profiles were determined by northern blot
      analysis and the relative expression of sstr2 by ribonuclease protection assay
      (RPA) and immunocytochemistry. Preoperative SRS visualised all primary breast
      cancer tumours. The scintigraphic image showed no correlation with the
      histopathological type of the tumour or with the abundance of
      oestrogen/progesterone receptors on the tumour. Two patients with a massive
      tumour infiltration of the lymph nodes had a distinct positive SRS of the
      ipsilateral axilla. In one patient with three nodal metastases the scintigraphic
      image of the axilla was weak but visible. Four other patients with a negative
      axillary scintigraphy had 1-2 lymph node metastases. The Ti/B ratios for the
      breast tumours varied between four and 33 and were not different from Ti/Br
      ratios. In lymph node metastases the Ti/B ratios were higher (10-41).
      Intraoperative detector measurements showed a significant difference between the
      breast tumour and normal tissue in 2/8 patients in situ. Similar measurements on
      excised tissues (ex vivo) showed a significant difference in 6/8 patients. Two
      patients with lymph node metastases exhibited a significantly increased uptake ex
      vivo by detector measurements, but in only one of them in situ. All tumour
      biopsies expressed the presence of sstrl, 3, 4 and 5, but not of sstr2 at
      northern analysis. On the other hand, sstr2 was detected in all tumours by RPA
      and immunocytochemistry. Preoperative SRS visualised primary breast cancer
      lesions in all 12 patients. SRS could also demonstrate extensive axillary tumour
      infiltration. Intraoperative use of the scintillation detector could not exclude
      axillary metastases in situ. The low Ti/B values of both primary tumours and
      metastases indicate limitations of the radiopharmaceutical used.

PMID- 12186372
TI  - Identification of angiogenesis in primary breast carcinoma according to the image
      analysis.
AB  - Tumor angiogenesis may be an independent prognostic factor for breast cancer
      survival. However, we can get the angiogenic property of the breast cancer only
      after the removal of breast tissue. To get this information before surgical
      resection of the tumor, we evaluated 29 breast carcinoma patients with Tc-99m
      MIBI scintimammography and power Doppler ultrasound (US) with a microbubble
      contrast agent preoperatively and compare their results with intratumoral
      microvessel density (IMD) and reverse transcriptase-polymerase chain reaction (RT
      PCR) of VEGF mRNA. IMD was well correlated with VEGF121 (r = 0.220, P = 0.024)
      and VEGF165 (r = 0.419, P = 0.046) mRNA level of the tumor. Power Doppler US
      grading of the tumor is well correlated with IMD (r = 0.552, P = 0.033). However,
      early uptake and washout index calculated from Tc-99m MIBI scintimammography
      showed no correlation with IMD or VEGF mRNA level, while washout index was
      inversely correlated with power Doppler US grading (r = -0.945, P = 0.001). In
      conclusion, the preoperative evaluation of breast cancer with power Doppler US
      with a microbubble contrast agent could predict tumor angiogenesis. Tc-99m MIBI
      scintimammography needs further study to use it as an image analysis for
      angiogenesis.

PMID- 12186373
TI  - Reversible and irreversible cardiac dysfunction associated with trastuzumab in
      breast cancer.
AB  - One of the newest agents used in the treatment of breast cancer is trastuzumab
      (Herceptin), a new recombinant DNA-derived humanized monoclonal antibody against
      the proto-oncogene, HER-2/neu gene product. However, despite its proven clinical
      efficacy, serious adverse effects leading to trastuzumab-induced cardiomyopathy
      have been described in up to 27% of patients receiving combination therapy with
      anthracyclines. There has been little published on the clinical syndrome of
      trastuzumab-induced cardiomyopathy. We describe three cases, of both reversible
      and irreversible cardiomyopathy, associated with the use of this novel and
      effective agent in HER-2 overexpressing breast cancer.

PMID- 12186374
TI  - Prognostic assessment of PTK activity in T1-T2, N0-N1, M0 breast cancer: a
      multicentric retrospective study.
AB  - Protein tyrosine kinases (PTKs) play a major role in the transduction of
      intracellular mitogenic signal. PTKs are also involved in the process of cellular
      transformation. A number of studies have reported increased PTK activities in
      cytosolic fractions from human breast carcinoma. However, the possible pronostic
      value of these activities is difficult to establish from these studies, mostly
      conducted on limited numbers of patients. In order to clear up the issue, we have
      investigated a large series of patients with a long follow-up, using a
      retrospective multicentric study (894 breast cancers T1-T2, N0-N1, M0; median
      follow-up: 67 months). PTKs were measured using a radioenzymatic assay as
      described in our previously report. We confirmed the already observed correlation
      between PTK activities and Scarff-Bloom grading (p < 10(-5)), negative estrogen
      receptor (ER), and progesterone receptor (PR) status. By contrast, we found in
      this study a correlation between PTK values and clinical nodal status (p =
      0.00027) not showed in our precedent analysis. In Cox multivariate analysis, PTK
      activity does not emerge as a significant pronostic parameter. On the other hand,
      tumor PTK activity assay may prove of great interest in clinical research using
      newly developed tyrosine kinase inhibitors in order to assess their biological
      impact and eventually to predict the responsiveness to these new therapeutic
      agents.

PMID- 12186375
TI  - Using cost-effectiveness analysis to define a breast cancer benefits package for
      the uninsured.
AB  - OBJECTIVES: In 1999, California was considering legislation to fund breast cancer
      treatment for its uninsured. We sought to define the most cost-effective breast
      cancer benefits package in order to inform this debate. METHODS: We use cost
      effectiveness analysis to calculate the additional costs and benefits of various
      adjuvant therapy strategies, radiation after breast conserving surgery, and
      reconstruction compared to those of surgery alone in order to define the most
      cost-effective breast cancer benefits package for uninsured women. RESULTS: Using
      cost-effectiveness analysis, we define a Minimum Breast Cancer Benefits Package
      that includes only the most cost-effective life-saving breast cancer treatments.
      To provide these benefits for an estimated 550 breast cancer patients will cost
      $10,200,000. We present two options that each cost an additional $1,700,000 - to
      expand the benefits to these patients to include post-mastectomy radiation and
      breast reconstruction; or to provide the Minimum Package to an additional 93
      uninsured women. CONCLUSIONS: California legislators must decide whether to offer
      comprehensive benefits to a limited number of breast cancer patients or to
      provide only the most life-saving treatments to a greater number of women.

PMID- 12186376
TI  - Novel therapeutic approach: ligands for PPARgamma and retinoid receptors induce
      apoptosis in bcl-2-positive human breast cancer cells.
AB  - Effective treatment of tumors is often associated with activation of the
      endogenous apoptosis pathways. We have studied eight breast cancer cell lines
      (MCF-7, BT20, BT474, MDA-MB-231, MDA-MB-436, SKBR3, T-47D, ZR-75-1) possessing a
      variety of genetic defects. The clonogenic growth of breast cancer cell lines was
      inhibited by a ligand for PPARgamma (troglitazone, TGZ) combined with a ligand
      for either retinoid X receptor (RXR) (LG10069) (4/8 cell lines), RAR (ATRA) (5/8
      cell lines) or RAR/RXR and RXR/RXR (9-cis-RA) (5/8 cell lines) independent of
      their expression of bcl-2, bag-1, ERalpha, and p53. The cell lines (MCF-7, T-47D,
      ZR-75-1), which expressed both BRCA1 and p27, were extremely sensitive to the
      inhibitory effect of the combination of TGZ and either ATRA or 9-cis-RA (ED90, 2
      5 x 10(-11) M). However, only MCF-7, MDA-MB-231, and ZR-75-1 cells, which
      expressed a high level of bcl-2 protein, underwent apoptosis when exposed to the
      combination of TGZ and either ATRA or 9-cis-RA. Importantly, this effect was
      independent of expression levels of p53, ERalpha, HER-2/neu, bag-1, and BRCA1.
      Therefore, the combination of ligands for PPARgamma and retinoid receptors may
      have a therapeutic role for breast cancer.

PMID- 12186377
TI  - Regulation of MCF-7 breast cancer cell growth by beta-estradiol sulfation.
AB  - Estrogen stimulation is an important factor in human breast cancer cell growth
      and development. Metabolism of beta-estradiol (E2), the major endogenous human
      estrogen, is important in regulating both the level and activity of the hormone
      in breast tissues. Conjugation of E2 with a sulfonate moiety is an inactivation
      process since the sulfate ester formed by this reaction can not bind and activate
      the estrogen receptor. In human tissues including the breast, estrogen
      sulfotransferase (EST, SULT1E1) is responsible for high affinity E2 sulfation
      activity. EST is expressed in human mammary epithelial (HME) cells but not in
      most cultured breast cancer cell lines, including estrogen responsive MCF-7
      cells. Stable expression of EST in MCF-7 cells at levels similar to those
      detected in HME cells significantly inhibits cell growth at physiologically
      relevant E2 concentrations. The mechanism of cell growth inhibition involves the
      abrogation of responses observed in growth factor expression in MCF-7 cells
      following E2 stimulation. MCF-7 cells expressing EST activity did not show a
      decrease in estrogen receptor-alpha levels, nor a characteristic increase in
      progesterone receptor or decrease in transforming growth factor-beta expression
      upon exposure to 100 pM or 1 nM E2. The lack of response in these MCF-7 cells is
      apparently due to the rapid sulfation and inactivation of free E2 by EST. These
      results suggest that loss of EST expression in the transformation of normal
      breast tissues to breast cancer may be an important factor in increasing the
      growth responsiveness of preneoplastic or tumor cells to estrogen stimulation.

PMID- 12186378
TI  - Overview of the pharmacology of the aromatase inactivator exemestane.
AB  - One third of all breast cancers and two thirds of postmenopausal breast cancers
      are estrogen dependent. Antiestrogen strategies, such as inhibition of estrogen
      receptor binding and estrogen deprivation, are effective for the management of
      hormone-dependent breast cancer. Although currently available agents are
      effective, the development of more potent and selective agents continues. Both
      steroidal and nonsteroidal inhibitors of aromatase have been developed for
      clinical uses. A novel class of steroidal irreversible antiaromatase agents
      demonstrates a high degree of specificity for the aromatase enzyme and exhibits a
      unique pharmacokinetic profile. The ability of these agents to inactivate
      aromatase may explain their high degree of potency and lengthy duration of
      action. Exemestane, an orally active aromatase inactivator, has demonstrated
      excellent selectivity and tolerability and broad-based efficacy in the treatment
      of postmenopausal breast cancer. Current findings suggest that exemestane will be
      a valuable alternative for women with breast cancer, not only for those
      progressing on other hormonal therapies but in earlier stages of the disease and
      prevention.

PMID- 12186379
TI  - Breast cancer-race, ethnicity, and survival: a literature review.
AB  - A review of the literature on breast cancer was conducted to identify gaps in
      knowledge as it relates breast cancer risk, race, and survival. The discussion
      has been divided into three broad categories: (1) breast cancer basics and the
      relationships between risks, race, and survival; (2) influence of race and
      socioeconomic status on breast cancer morbidity and mortality; and (3)
      relationship between age and mammography screening. All of the cited studies
      reveal evidence of a linkage between race and breast cancer survival, however,
      the effects of socioeconomic factors and race needs to be examined. Results
      suggest that African-American women and lower income women need to be targeted
      for early detection. Many of the analyses among younger women (20-39 years)
      reported that very little disease occurrence in young black women was associated
      with the socioeconomic factors studied. Conclusions from all studies indicate
      that more aggressive screening and public education programs directed toward
      younger black women is warranted. The gaps in knowledge identified included the
      lack of an explanation of early onset breast cancer with high penetrance as well
      as an explanation of African-American women's resistance to self-examination and
      mammography screening and other barriers to diagnostic treatment. Future studies
      should also examine the link between familial breast cancer and genetic
      mutations.

PMID- 12186380
TI  - Determination of 1-hydroxypyrene in human urine by high-performance liquid
      chromatography with fluorescence detection using a deuterated internal standard.
AB  - A high-performance liquid chromatographic method has been developed for the
      quantification of 1-hydroxypyrene (1-OHP) in human urine using deuterated 1
      hydroxypyrene ([2H9]1-OHP) as an internal standard with fluorescence detection.
      [2H9]1-OHP was prepared enzymatically from deuterated pyrene ([2H10]Pyr) with
      cytochrome P450 1A1. It eluted immediately prior to non-deuterated 1-OHP on
      alkylamide-type reversed-phase columns and had nearly the same fluorescence
      characteristics as non-deuterated 1-OHP. The detection limit was 0.1 microg/L and
      the calibration range was from 1 to 100 nmol/L. Urine sample treatment involved
      enzymatic hydrolysis followed by solid-phase extraction using Sep-Pak C18
      cartridges. The proposed method was used to determine urinary 1-OHP in smokers
      and non-smokers.

PMID- 12186381
TI  - Immobilized liposome chromatography to study drug-membrane interactions.
      Correlation with drug absorption in humans.
AB  - For rapid screening of drug-membrane interactions and predicting drug absorption
      in vivo, unilamellar liposomes were stably immobilized in the pores of gel beads
      by avidin-biotin binding. Interactions of a diverse set of well-described drugs
      with the immobilized liposomal membranes were reflected by their elution
      profiles. The membrane partitioning coefficients (KLM) of the drugs were
      determined from the retention volumes. The drug retentions on egg
      phosphatidylcholine (EPC)-phosphatidylserine (PS)-cholesterol (chol) and EPC-PS
      phosphatidylethanolamine (PE)-chol columns intended to mimic small intestine
      membranes were similar, although the positively-charged drugs were more strongly
      retarded on the negatively-charged liposomes than the negatively-charged drugs.
      The relationship between log KLM with the drug fraction absorbed in humans showed
      that the log KLM values obtained with unilamellar liposomes can be used to
      predict drug passive transcellular absorption, similarly to that previously shown
      for entrapped multilamellar liposomes. The immobilized liposome chromatography
      method should be useful for screening compounds at an early stage of the drug
      discovery process. The avidin-biotin immobilization of the liposomes prolongs the
      lifetime of the columns.

PMID- 12186382
TI  - Determination and pharmacokinetic study of meropenem in rat bile using on-line
      microdialysis and liquid chromatography.
AB  - Meropenem is a carbapenem antibiotic with a wide spectrum of activity against
      both Gram-positive and Gram-negative bacteria. Because of its clinical efficacy,
      meropenem is an excellent choice for the treatment of serious infections in both
      adults and children. The knowledge of tissue concentrations of antibiotic in an
      infection site is valuable for the prediction of treatment outcome. To
      investigate the biliary disposition of meropenem, we utilized a minimally
      invasive sampling technique with a shunt linear microdialysis probe for
      continuous sampling in the biliary excretion studies. Analysis of meropenem in
      the dialysates was achieved using a LiChrosorb RP-18 column (Merck, 250 x 4.6 mm
      I.D.; particle size 5 microm) maintained at ambient temperature. The mobile phase
      was 50 mM monosodium phosphoric acid-methanol (80:20, v/v, pH 3.0). The UV
      detector wavelength was set at 298 nm. The area under the concentration-time
      curve and elimination half-lives of meropenem were about 6144 +/- 1494 min
      microg/ml and 61 +/- 17 min, respectively. This study represents a successful
      application of the microdialysis technique, which is an effective method for
      pharmacokinetic and biliary drug excretion studies.

PMID- 12186383
TI  - Simultaneous determination of berberine in rat blood, liver and bile using
      microdialysis coupled to high-performance liquid chromatography.
AB  - High-performance liquid chromatography coupled to microdialysis was used for the
      simultaneous determination of unbound berberine in rat blood, liver and bile for
      a pharmacokinetic study. Microdialysis probes were simultaneously inserted into
      the jugular vein toward the right atrium, the median lobe of the liver, and the
      bile duct of male Sprague-Dawley rats for biological fluid sampling after
      administration of berberine (10 mg/kg) through the femoral vein. Berberine and
      dialysates were separated using a Zorbax SB-phenyl column and a mobile phase
      comprised of acetonitrile-methanol-20 mM monosodium phosphate (pH 3.0) (35:20:45,
      v/v) together with 0.1 mM 1-octanesulfonic acid. The detection limit for
      berberine was 10 ng/ml. The concentration-response relationship was linear (r2 >
      0.995) over the concentration range 0.05-50 microg/ml; intra-assay and inter
      assay precision and accuracy for berberine fell within predefined limits. The
      disposition of berberine in the blood, liver and bile fluid suggests that
      berberine might be metabolized in the liver and undergo hepatobiliary excretion.

PMID- 12186384
TI  - Pharmacokinetic study of levofloxacin in rat blood and bile by microdialysis and
      high-performance liquid chromatography.
AB  - The aim of this study was to develop a rapid and sensitive method for the
      simultaneous determination of unbound levofloxacin in rat blood and bile using
      high-performance liquid chromatography coupled with microdialysis for further
      pharmacokinetic study. Microdialysis probes were simultaneously inserted into the
      jugular vein toward the right atrium and the bile duct of male Sprague-Dawley
      rats for biological fluid sampling after administration of levofloxacin 3 mg/kg
      through the femoral vein. Levofloxacin and dialysates were separated using a
      Merck LiChrospher reversed-phase C18 column maintained at ambient temperature.
      The mobile phase was comprised of acetonitrile-1 mM 1-octanesulfonic acid (40:60,
      v/v, pH 3.0 adjusted with orthophosphoric acid). The fluorescence response for
      levofloxacin was observed at excitation and emission wavelengths of 292 and 494
      nm, respectively. The detection limit of levofloxacin was 50 ng/ml. Intra-day and
      inter-day precision and accuracy of levofloxacin measurements fell well within
      the predefined limits of acceptability. The disposition of levofloxacin in the
      blood and bile fluid suggests that there was rapid exchange and equilibration
      between the blood and hepatobiliary systems, and the plasma level of levofloxacin
      was greater than that of the bile. Thus, levofloxacin undergoes hepatobiliary
      excretion but might not be related to the P-glycoprotein transport system.

PMID- 12186385
TI  - Characterization of the refolding and reassembly of an integral membrane protein
      OmpF porin by low-angle laser light scattering photometry coupled with high
      performance gel chromatography.
AB  - The refolding and reassembly of an integral membrane protein OmpF porin denatured
      in sodium dodecylsulfate (SDS) into its stable species by the addition of n-octyl
      beta-D-glucopyranoside (OG) have been studied by means of circular dichroism (CD)
      spectroscopy and low-angle laser light scattering photometry coupled with high
      performance gel chromatography. The minimal concentration where change in the
      secondary structure was induced by the addition of OG was found to be 6.0 mg/ml
      in CD experiments. A species unfolded further than the SDS-denatured form of this
      protein was observed at an early stage (5-15 min) of refolding just above the
      minimal OG concentration. In addition, the CD spectrum of protein species
      obtained above the minimal OG concentration showed that the protein is composed
      of a beta-structure which is different from the native structure of this protein.
      In light scattering experiments, no changes in molecular assemblies were observed
      when the OG concentration was below its minimal refolding concentration
      determined by CD measurements. Above the minimal concentration, a compact
      monomeric species was observed when denatured OmpF porin was incubated for 5 min
      at 25 degrees C in a refolding medium containing 1 mg/ml SDS and 7 mg/ml OG, and
      then injected into columns equilibrated with the refolding medium. After an
      incubation of 24 h before injection into the columns, predominant dimerization of
      this protein was observed in addition to incorrect aggregation.

PMID- 12186386
TI  - One-step capillary isoelectric focusing of the proteins in cerebrospinal fluid
      and serum of patients with neurological disorders.
AB  - One-step capillary isoelectric focusing (cIEF), which uses reduced but non-zero
      electroosmosis flow to mobilize the focused proteins, was applied to the analysis
      of proteins in cerebrospinal fluid (CSF) and serum of patients with various
      neurological disorders. Under the conditions employed, pathological changes in
      the CSF proteins were clearly detected on the electropherograms within 25 min,
      although the serum proteins did not vary significantly between samples. The
      present one-step cIEF system seems to be useful in routine laboratory
      examinations of a large number of CSF samples as an aid in neurological
      diagnosis.

PMID- 12186387
TI  - New model of surface diffusion in reversed-phase liquid chromatography.
AB  - A new model of surface diffusion in reversed-phase liquid chromatography (RPLC)
      was derived by assuming a correlation between surface and molecular diffusion.
      Analysis of surface diffusion data under different conditions of sample
      compounds, mobile and stationary phases, and temperature in RPLC systems
      validates this assumption and shows that surface diffusion should be regarded as
      a molecular diffusion restricted by the adsorptive interactions between the
      adsorbate molecule and the stationary phase surface. A surface-restricted
      molecular diffusion model was proposed as a first approximation for the mechanism
      of surface diffusion. The model is formulated according to the absolute rate
      theory. The activation energy of surface diffusion (Es) was quantitatively
      interpreted assuming that Es consists of the contributions of two processes, a
      hole-making and a jumping one. The former contribution is nearly equal to the
      activation energy of molecular diffusion and is correlated with the evaporative
      energy of the mobile phase solvent. The latter contribution is a fraction of the
      isosteric heat of adsorption. An appropriate explanation based on this new model
      of surface diffusion is provided for two contradictory results related to the
      relationship between retention equilibrium and surface diffusion in RPLC and to
      the surface diffusion coefficient for weakly retained sample compounds.

PMID- 12186388
TI  - Capillary magnetophoresis of human blood cells and their magnetophoretic trapping
      in a flow system.
AB  - The performance of a capillary magnetophoretic device was improved by enhancing
      the magnetic field gradient using a pair of small iron tips attached to the Nd-Fe
      B magnets. The magnetophoretic intensity, B(dB/dx), was determined as a function
      of distance along the gap between the tips from the magnetophoretic velocity of a
      3 microm polystyrene microparticle in 0.6 M manganese(II) chloride solution. The
      maximum intensity was increased 4.5 times by the attached iron pieces. The
      magnetophoresis of a single human blood cell in 0.1 M manganese(II) solution was
      studied by this method and its magnetic susceptibility was estimated.
      Magnetophoretic trapping of red blood cells was demonstrated under counter
      current flow conditions in the capillary.

PMID- 12186389
TI  - Improvement of the long-term stability of polyimide-coated fused-silica
      capillaries used in capillary electrophoresis and capillary
      electrochromatography.
AB  - Swelling of the polyimide coating of fused-silica capillaries in acetonitrile
      containing buffers was found to be the reason for several problems in capillary
      electrophoresis (CE) and capillary electrochromatography (CEC). Scanning electron
      microscopy photographs of the ends of raw fused-silica tubing showed that the
      coating becomes soft and increases its volume after longer contact with such
      buffers. As a consequence, separation efficiency can deteriorate, the capillary
      ends can clog or break off. To prevent swelling of the polyimide coating, fused
      silica capillaries used in CE or CEC were heated at 300 degrees C for a longer
      period of time which improved their long-term stability in comparison to raw
      fused-silica tubing.

PMID- 12186390
TI  - Effect of preparatory conditions on the performance of photopolymerized sol-gel
      monoliths for capillary electrochromatography.
AB  - We prepared different photopolymerized sol-gel (PSG) columns by varying the
      amount of monomer (methacryloxypropyltrimethoxysilane), porogen (toluene) and
      catalyst (hydrochloric acid) in the reaction solution containing a photoinitiator
      (Irgacure 1800). The effects of these variations on the chromatographic behavior
      of the PSG columns were studied. All of the columns studied exhibited reversed
      phase character. The concentration of hydrochloric acid was important for the
      rigidity of the columns, although it did not affect the separation property. The
      ratio of monomer solution to porogen was a critical factor in controlling the
      through-pore size and the surface area of PSG, which were found to significantly
      affect the separation properties, such as permeability, theoretical plate number,
      retention time, and separation efficiency, of a mixture of test analytes
      thiourea, benzene, and naphthalene. There was no change in the retention order
      for the test analytes. Short separation times were achieved on PSG columns made
      from a 10% monomer stock solution and 90% porogen with 1 M hydrochloric acid.
      Mixtures of polycyclic aromatic hydrocarbons and alkylbenzenes were separated
      with theoretical plate numbers greater than 100 000 plates/m.

PMID- 12186391
TI  - Monolithic silica columns with various skeleton sizes and through-pore sizes for
      capillary liquid chromatography.
AB  - Reduction of through-pore size and skeleton size of a monolithic silica column
      was attempted to provide high separation efficiency in a short time. Monolithic
      silica columns were prepared to have various sizes of skeletons (approximately 1
      2 microm) and through-pores (approximately 2-8 microm) in a fused-silica
      capillary (50-200 microm I.D.). The columns were evaluated in HPLC after
      derivatization to C18 phase. It was possible to prepare monolithic silica
      structures in capillaries of up to 200 microm I.D. from a mixture of
      tetramethoxysilane and methyltrimethoxysilane. As expected, a monolithic silica
      column with smaller domain size showed higher column efficiency and higher
      pressure drop. High external porosity (> 80%) and large through-pores resulted in
      high permeability (K = 8 x 10(-14) -1.3 x 10(-12) m2) that was 2-30 times higher
      than that of a column packed with 5-mirom silica particles. The monolithic silica
      columns prepared in capillaries produced a plate height of about 8-12 microm with
      an 80% aqueous acetonitrile mobile phase at a linear velocity of 1 mm/s.
      Separation impedance, E, was found to be as low as 100 under optimum conditions,
      a value about an order of magnitude lower than reported for conventional columns
      packed with 5-microm particles. Although a column with smaller domain size
      generally resulted in higher separation impedance and the lower total
      performance, the monolithic silica columns showed performance beyond the limit of
      conventional particle-packed columns under pressure-driven conditions.

PMID- 12186392
TI  - Analysis of the herbicides paraquat, diquat and difenzoquat in drinking water by
      micellar electrokinetic chromatography using sweeping and cation selective
      exhaustive injection.
AB  - Optimum conditions for the determination of the herbicides paraquat, diquat and
      difenzoquat by micellar electrokinetic chromatography (MEKC) using sweeping and
      cation-selective exhaustive injection (CSEI) as on-line concentration methods
      were developed. Sodium dodecyl sulfate (80 mM) in 50 mM phosphate buffer (pH 2.5)
      with 20% acetonitrile was used as a background electrolyte for the methods
      studied. The limits of detection, based on a signal-to-noise ratio of 3:1, were
      about 2.6-5.1 mg 1(-1) in purified water when MEKC was applied for the standards.
      By using an on-line preconcentration method known as sweeping-MEKC, up to a 500
      fold increase in detection sensitivity was obtained whereas up to a 50 000-fold
      increase for CSEI-sweeping-MEKC was achieved. The limits of detection using
      optimum CSEI-sweeping-MEKC were lower than 1 microg 1(-1) and the method was
      validated obtaining good reproducibility (relative standard deviation lower than
      22%) and linearity. CSEI-sweeping-MEKC was successfully applied to the
      determination of the three herbicides in spiked tap water below the levels
      established by the US Environmental Protection Agency.

PMID- 12186393
TI  - Simultaneous analysis of monosaccharides and oligosaccharides by high-performance
      liquid chromatography with postcolumn fluorescence derivatization.
AB  - To develop a fluorimetric HPLC technique for the simultaneous microanalysis of
      reducing mono- and oligosaccharides, the technique of linear gradient elution was
      introduced into the postcolumn fluorimetric detemination system of reducing
      saccharides with benzamidine. Fluorescence measurement was performed at 288 nm
      for excitation and 470 nm for emission and an optimization study for this
      postcolumn fluorescence derivatization carried out. Under optimum conditions, the
      detection limits of D-glucose and maltohexaose were 1.78 and 2.59 pmol,
      respectively. The present method was successfully applied to saccharide analysis
      and should prove useful for automated simultaneous microanalysis of reducing mono
      and oligosaccharides in foods.

PMID- 12186394
TI  - Identification and determination of geniposide contained in Gardenia jasminoides
      and in two preparations of mixed traditional Chinese medicines.
AB  - A high-performance liquid chromatographic method was applied to the determination
      of the geniposide concentration in Gardenia fruit and preparations of traditional
      Chinese medicine using a mobile phase of acetonitrile-methanol-5 mM monosodium
      phosphate (pH 4.6) (5:15:80, v/v/v). Intra-assay and inter-assay accuracy and
      precision of the analyses were < or = 10% in the range of 0.1 through 50
      microg/ml. The presence of geniposide in the medicinal herb and its preparations
      was ascertained by retention time, spiking with an authentic standard, change of
      detection wavelength and change of the composition of the mobile phase. The
      concentration of geniposide in the fruit of Gardenia jasminoides Ellis var.
      grandiflora Nakai is higher than that in Gardenia jasminoides Ellis. The
      concentration of geniposide in the traditional Chinese herbal medicine
      preparations, Huang-Lian-Jiee-Dwu-Tang (66.27 +/- 1.98 mg/g) and In-Chern-Hau
      Tang (68.54 +/- 2.62 mg/g) was less than in the herb Gardenia jasminoides Ellis
      (73.44 +/- 2.62 mg/g) itself.

PMID- 12186395
TI  - High-performance liquid chromatographic separation of carbohydrates on a
      stationary phase prepared from polystyrene-based resin and novel amines.
AB  - New anion-exchange stationary phases On (n = 1, 2 and 3) with a dimethylamino
      terminal functional group, where n is the number of oxyethylene units [
      (CH2CH2O)n-], were prepared by the reaction of chloromethylated porous styrene
      divinylbenzene copolymer beads and amines [(CH3)2N-(CH2CH2O)nCH2CH2-N(CH3)2].
      HPLC separations of monosaccharides (sorbitol, fucose, glucosamine, mannose,
      glucose, galactose, fructose, allose and altrose) and disaccharides (trehalose,
      lactose, cellobiose and maltose) were performed successfully on these stationary
      phases. The ether group of the stationary phases On was found to affect the
      separation of carbohydrates.

PMID- 12186396
TI  - A comparative study of commercial liquid chromatographic detectors for the
      analysis of underivatized amino acids.
AB  - This study compares the main commercial detectors that can detect amino acids in
      their underivatized form. The detectors tested are: the chemiluminescent nitrogen
      detector (CLND), the evaporative light scattering detector (ELSD), the nuclear
      magnetic resonance spectrometer, conductivity detector, refractive index, UV, and
      electrospray quadrupole mass spectrometry (in simple and tandem MS mode). As
      ELSD, CLND and MS require a volatile mobile phase, an ion-pair reversed-phase
      liquid chromatographic system was selected, consisting of an octadecyl column and
      an aqueous mobile phase containing pentadecafluorooctanoic acid as volatile ion
      pairing reagent. Underivatized taurine, hypotaurine, aspartic acid,
      hydroxyproline, asparagine, serine, glycine, glutamine, cysteine, glutamic acid,
      threonine and alanine were simultaneously analysed with each detector. In order
      to test the applicability of these detectors to "real world" samples, the amino
      acid stoichiometry of the tetrapeptide Gly-Gly-Asp-Ala was determined with each
      detector after acid hydrolysis. The detectors were compared in terms of
      linearity, limit of detection, advantages and disadvantages as well as special
      features (capacity to provide structural information, specificity, quantification
      with single calibration curve, etc.).

PMID- 12186397
TI  - Identification of dehydroepiandrosterone metabolites formed from human prostate
      homogenate using liquid chromatography-mass spectrometry and gas chromatography
      mass spectrometry.
AB  - The identification of the in vitro metabolites of dehydroepiandrosterone formed
      from human prostate homogenate was investigated by hyphenated techniques using
      the stable-isotope dilution method. A mixture of dehydroepiandrosterone and
      [2H4]dehydroepiandrosterone was incubated with hypertrophied human prostate
      tissue homogenate in the presence of NAD, NADH and NADPH. The metabolites were
      extracted with AcOEt-hexane, purified by solid-phase extraction, and then
      analyzed by LC-atmospheric pressure chemical ionization MS and/or GC-MS. Androst
      5-ene-3beta,17beta-diol (major product), androst-4-ene-3,17-dione, testosterone,
      5alpha-dihydrotestosterone, androsterone, and 7alpha
      hydroxydehydroepiandrosterone were identified in comparison with authentic
      samples based on their chromatographic behavior and mass spectra.

PMID- 12186398
TI  - Effects of the aqueous extract of Epimedii Herba on the induction of oral
      tolerance in mice.
AB  - We investigated the effects of the aqueous extract of Epimedii Herba (AEEH) on
      the induction of oral tolerance. Oral tolerance was induced in mice by giving an
      oral administration of 20 mg ovalbumin (OVA) 7 d before immunization with the
      antigen. AEEH at 40 mg/kg was given orally daily for 6 d from 24 h after the
      feeding of OVA. The results showed that oral administration of OVA greatly
      suppressed total serum and antigen-specific immunoglobulin (Ig) levels,
      phagocytic activity and delayed-type hypersensitivity (DTH) reaction to the
      antigen. The suppression of these immune responses to OVA by the oral antigen was
      associated with a marked reduction of the production of interferon-gamma (IFN
      gamma) and interleukin-4 (IL-4) from spleen cells. However, AEEH treatment
      significantly blocked the suppression of total serum and antigen-specific IgG2a
      antibodies, phagocytic activity and DTH response by the oral OVA. The suppression
      of IFN-y production by the oral antigen was also greatly decreased by AEEH
      treatment. Therefore, AEEH appears to be effective in preventing the induction of
      oral tolerance to OVA.

PMID- 12186399
TI  - Comparative studies of a humanized anti-glycoprotein IIb/IIIa monoclonal
      antibody, YM337, and abciximab on in vitro antiplatelet effect and binding
      properties.
AB  - The effects of YM337, the Fab fragment of a humanized anti-glycoprotein IIb/IIIa
      (GPIIb/IIIa) monoclonal antibody C4G1, on in vitro platelet function and binding
      properties were compared with those of abciximab, the Fab fragment of the
      human/murine chimeric anti-GPIIb/IIIa monoclonal antibody 7E3. Both agents
      completely inhibited platelet aggregation caused by all agonists tested except
      ristocetin. Further, both inhibited human platelet adhesion to von Willebrand
      factor, fibrinogen, fibronectin and subendothelial matrix with similar potency.
      Fibrinogen binding to washed platelets was dose-dependently inhibited by both
      agents. In binding assay using 125I-YM337 and 125I-abciximab, Kd values
      determined with platelet-rich plasma were 6.74 +/- 0.56 nM for YM337 and 6.65 +/-
      1.45 nM for abciximab, and the number of binding sites were 42,700 +/- 3,000 for
      YM337 and 76,000 +/- 5,400 for abciximab. GPIIb/IIIa was precipitated from the
      solubilized fraction of platelets by both agents. In contrast, integrin
      alphavbeta3 was precipitated from the solubilized fraction of human umbilical
      vein endothelial cells by abciximab but not by YM337. Fibrinogen binding to
      purified GPIIb/IIIa was dose-dependently inhibited by both agents. In contrast,
      vitronectin binding to purified integrin alphavbeta3 was dose-dependently
      inhibited by abciximab but not by YM337, supporting the idea that abciximab
      reacts to integrin alphavbeta3. Therefore, YM337 was suggested to bind to a
      different epitope of GPIIb/IIIa from abciximab. These results suggest that YM337
      specifically acts on platelet GPIIb/IIIa receptors and has similar inhibitory
      properties on platelet aggregation and platelet adhesion to abciximab.

PMID- 12186400
TI  - Elenoside, a new cytotoxic drug, with cardiac and extracardiac activity.
AB  - This paper deals with the effects of elenoside, (3-hidroxymethyl-1-methoxy-5,6
      methylene-dioxy-4-(3,4-methylenedioxyphenyl)-2-naftoic acid lactone-beta-D
      glucoside) an arylnaphthalene lignan with broad spectrum cytotoxicity in a human
      tumor cell line panel, isolated from Justicia hyssopifolia (Acanthaceae) grown in
      the Canary Islands (Spain), on isolated cardiac auricle of rabbits, urinary
      excretion of rats, and on isolated rat ileum. These effects, using a vehicle
      (propylene glycol-ethanol-plant oil-Tween 80 (40:10:50:2) as a standard, are
      presented. Elenoside at concentrations of 3.2x10(-4), 6.4 x 10(-4), and 1.2 x 10(
      3) M produced an increase in the contraction force of auricles in a concentration
      dependent way. At doses of 25 and 50 mg/kg, an antidiuretic effect and a decrease
      in sodium excretion were observed. Elenoside at concentrations of 3.2 x 10(-4),
      6.4 x 10(-4) and 1.2 x 10(-3) M produced an increase in the contraction force of
      ileum in a concentration-dependent manner. Elenoside produced the concentration
      dependent inhibition of 86Rb uptake. These results indicate that elenoside has
      digitalis-like activity similar to mammalian lignans. Moreover, this lignan has
      an irritant effect on the gastrointestinal tract.

PMID- 12186401
TI  - Lumin, a cyanine dye, enhances interleukin 12-dependent interferon gamma
      production by lipopolysaccharide-stimulated mouse splenocytes.
AB  - Lumin was orally administered to mice daily for 3 d, and on the day following the
      final administration, mice were sacrificed and splenocytes were stimulated with
      lipopolysaccharide (LPS). Splenocytes obtained from lumin-treated mice showed
      enhanced production of interferon gamma (IFN-gamma) and increased percentages of
      CD3+ cells. Although T cells are considered to be the source of IFN-gamma, it is
      unlikely that LPS directly stimulates T cells. Next we performed neutralization
      experiments using a monoclonal antibody (mAb) against interleukin (IL-)12 because
      this cytokine, which is produced by macrophages, has the direct ability to induce
      IFN-gamma production and the proliferation of activated T cells. This antibody
      inhibited IFN-gamma production by splenocytes. We thus show that orally
      administered lumin enhances IFN-gamma production by splenocytes when the latter
      are stimulated with LPS, a phenomenon that was observed in correlation with
      activation of T cells by IL-12, that is produced by macrophages.

PMID- 12186402
TI  - Effects of rinbacin extract on rat kidney.
AB  - The aqueous leaf extract of rinbacin was tested for toxic effects on prepubertal
      rat kidneys following chronic administration. Two doses of rinbacin extract
      (26.25 g/l and 52.50 g/l) were administered in the rats' drinking water for 13
      weeks, and various toxicologic indices tested. Histological study of the kidneys
      was also carried out at the expiration of the test period. Rinbacin at both dose
      sizes significantly (p<0.05) increased the absolute and relative kidney weights.
      Also the serum HCO3- level was significantly (p<0.05) increased, while the serum
      K+ level was decreased significantly at both dose levels. Only the high dose
      significantly (p<0.05) increased the serum urea level of the rats. Histological
      study showed that rinbacin at both dose sizes caused renal pathologic changes,
      which included necrosis and cellular infiltration of glomeruli and epithelia of
      the tubules. The effects were less marked in the low dose than the high dose
      group. Chronic administration of rinbacin extract induces nephrotoxicity in young
      rats.

PMID- 12186403
TI  - Evaluation of carcinogenic/co-carcinogenic activity of chikusaku-eki, a bamboo
      charcoal by-product used as a folk remedy, in BALB/c 3T3 cells.
AB  - Chikusaku-eki is an acidic dark brown liquid obtained as a by-product from bamboo
      charcoal burners. The solution diluted with water is gaining widespread
      popularity in Japan as a folk medicine for skin diseases such as scabies, eczema,
      and atopic dermatitis. In this study, the carcinogenic and tumor-promoting
      potential of chikusaku-eki was determined using the BALB/c 3T3 A31-1-1 cell
      transformation system. Carcinogenic activity was tested by treating A31-1-1 cells
      for 24 h with 0.06% solution, a dose resulting in 35% clonogenic cell survival.
      In both 2-O-tetradecanoylphorbol-13-acetate (TPA)-treated and non-treated groups,
      chikusaku-eki did not initiate carsinogenesis. Following initiation with 3
      methylcholanthrene (3-MCA), A31-1-1 cells were chronically treated with a non
      toxic concentration range of chikusaku-eki (< or = 0.01%), but chikusaku-eki did
      not act as a tumor promoter. Thus, chikusaku-eki was not carcinogenic/co
      carcinogenic in the in vitro cell transformation assay examined in this study
      after being diluted more than 10(4)-fold with water.

PMID- 12186404
TI  - Antinociceptive effects of 1-acyl-4-dialkylaminopiperidine and 1-alkyl-4
      dialkylaminopiperidine in mice: structure-activity relation study of matrine-type
      alkaloids.
AB  - We previously reported that (+)-matrine and (+)-allomatrine have antinociceptive
      properties mediated mainly through the activation of kappa-opioid receptors. 1
      Acyl-4-dialkylaminopiperidines were synthesized as the simplest derivatives of
      matrine, and the structure-activity relations were examined by the acetic acid
      induced abdominal contraction test. The antinociceptive potencies of 1-alkyl-4
      dialkylaminopiperidines were significantly lower than those of the corresponding
      1-acyl-4-dialkylaminopiperidines. These findings suggest that the amide group of
      (+)-matrine is an essential functional group that influences antinociceptive
      potency.

PMID- 12186405
TI  - Authentication of oviductus ranae and its original animals using molecular
      marker.
AB  - Two pairs of diagnostic primers, IHm01-L/IHm01-H and IHm02-L/IHm02-H, for
      distinguishing the Chinese crude drug Oviductus Ranae from its substitutes were
      designed based on sequences of Cyt b gene fragment of the original animals of the
      drug and substitutes. Total DNAs were extracted from crude drugs purchased from
      five drugstores in different regions, as well as from original animals of the
      drug, Rana chensinensis, and seven species of related ranid species. Diagnostic
      polymerase chain reactions (PCRs) were performed using the two pairs of primers
      with the total DNAs of the original animals as a template. The result showed that
      a 240 bp DNA segment was clearly amplified from all templates of Rana
      chensinensis using primers IHmO1-L and IHm01-H, whereas no DNA band appeared from
      other templates. While using primers IHm02-L and IHm02-H, we got a clear 140 bp
      DNA band from all the templates of R. huanrenensis and 3 oviducts of the same
      species, no PCR product was observed from the other samples. A set of PCR
      reactions was employed to identify crude drugs from the five drugstores using the
      two pairs of primers together with HsmL1 and HsmH1 reported in our previous
      study. The results show that only 20% of the Oviductus Ranae currently sold in
      markets are qualified products and the rest are not.

PMID- 12186406
TI  - Stimulative effects of (22E,24R)-ergosta-7,22-diene-3beta,5alpha,6beta-triol from
      fruiting bodies of Tricholoma auratum, on a mouse osteoblastic cell line, MC3T3
      E1.
AB  - We screened the differentiation-inducing activities of 39 mushroom extracts from
      Akita prefecture, Japan, on the mouse osteoblastic cell line, MC3T3-E1. Sixteen
      phosphate buffered saline (PBS), 8 boiled PBS, 14 ethanol and 12 methanol
      extracts induced alkaline phosphatase (ALP) activities, an indicator of MC3T3-E1
      cell differentiation. The enzyme activities were markedly induced by extracts of
      Tricholoma auratum, and we isolated the active compound from methanol extracts of
      this mushroom. Physical data for the isolated active compound were identical to
      those for (22E,24R)-ergosta-7,22-diene-3beta,5alpha,6beta-triol (1). 1 induced
      ALP activities of MC3T3-E1 cells and promoted cell proliferation. To investigate
      the relationships between the chemical structure and differentiation-inducing
      activity of the compound, ALP-inducing activities of MC3T3-E1 cells by 1,
      ergosterol (2), ergocalciferol (3), cholesta-3beta3,5alpha6beta-triol (4), 7
      dehydrocholesterol (5) and cholecalciferol (6) were tested. The enzyme activities
      of MC3T3-E1 cells were increased 3.0-fold by 10 microM 1 and 2.4-fold by 10
      microM 4. However, 2, 3, 5 and 6 did not induce MC3T3-E1 cell ALP activity at 0.1
      10 microM. These results suggested that the OH groups at C-5 and/or C-6 of 1 and
      4 played an important role in their differentiation-inducing activities on MC3T3
      E1 cells. Furthermore, 1 suppressed induction of MC3T3-E1 cell apoptosis by serum
      starvation.

PMID- 12186407
TI  - Mulberroside F isolated from the leaves of Morus alba inhibits melanin
      biosynthesis.
AB  - The current study was carried out to investigate the in vitro effects of an 85%
      methanol extract of dried Morus alba leaves on melanin biosynthesis, which is
      closely related to hyperpigmentation. These extracts inhibited the tyrosinase
      activity that converts dopa to dopachrome in the biosynthetic process of melanin.
      Mulberroside F (moracin M-6, 3'-di-O-beta-D-glucopyranoside), which was obtained
      after the bioactivity-guided fractionation of the extracts, showed inhibitory
      effects on tyrosinase activity and on the melanin formation of melan-a cells.
      This compound also exhibited superoxide scavenging activity that is involved in
      the protection against auto-oxidation. But its activity was low and was weaker
      than of kojic acid. These results suggest that mulberroside F isolated from
      mulberry leaves might be used as a skin whitening agent.

PMID- 12186408
TI  - Prolyl endopeptidase inhibitors from the roots of Lindera strychnifolia F. Vill.
AB  - Prolyl endopeptidase (PEP, EC 3.4.21.26) has been proposed to play a role in
      degradation of proline-containing neuropeptides involved in the processes of
      learning and memory, e.g., vasopressin, substance P, and thyrotropin-releasing
      hormone (TRH). In the course of our search for bioactive constituents in
      medicinal plants, we studied the PEP inhibitory constituents of the roots of
      Lindera strychnifolia F. VILL and isolated two known tannins, epicatechin (1) and
      aesculitannin B (2), and four known sesquiterpenes, linderene (3), linderene
      acetate (4), linderalactone (5) and isolinderalactone (6) as inhibitors. On the
      inhibitory activities of six compounds against PEP from Flavobacterium
      meningosepticum and that from rat brain supernatant, compounds 1, 2 and 4
      inhibited the enzyme from Flavobacterium more strongly than that from rat brain
      supernatant. However, compounds 3, 5 and 6 inhibited the enzymes from both
      origins to the same extent and furthermore, compound 6 was the strongest natural
      inhibitor against PEP from rat brain supernatant. The kinetic study of these
      inhibitors indicated that compounds 1, 2 are noncompetitive inhibitors and
      compounds 3-6 are competitive inhibitors. This is the first example of non
      phenolic constituents showing significant competitive inhibitory activity being
      isolated from natural medicines.

PMID- 12186409
TI  - Effects of extract derived from Eriobotrya japonica on liver function improvement
      in rats.
AB  - Eriobotrya japonica is considered a medicinal plant, and its leaves (Eriobotrya
      folia) have been used to treat skin diseases, as well as to relieve inflammation,
      pain, coughing, and sputa. In our evaluation of the pharmacological efficacy of
      the seed extracts, constituents of the seeds were found to contain the
      unsaturated fatty acids linolenic and linoleic acids and the sterol beta
      sitosterol in the 70% EtOH and the MeOH extracts. The seed extracts were orally
      administered to rats with dimethylnitrosamine-induced hepatopathy, and blood L
      asparate aminotransferase (AST) and L-alanine aminotransferase (ALT) levels,
      liver retinoid level, and hydroxyproline level were measured. Liver fibrosis
      rates calculated after Azan-Mallory staining and evaluation of the liver function
      improving effects of extracts were showed that AST, ALT, and hydroxyproline
      levels and liver fibrosis rates were significantly lower, and retinoid levels
      were significantly higher in hepatopathic rats treated with 70% EtOH and MeOH
      extracts of the seed than in water-treated control rats. This suggests that the
      positive effect on liver function of the extracts varies depending on the
      extracting solvent used. 70% EtOH and MeOH extract of the seeds inhibited the
      development of liver fibrosis in hepatopathic rats, thus exhibiting potent
      improvement. The unsaturated linolenic and linoleic acids and the sterol beta
      sitosterol contained in these extracts may also contribute to the improvement of
      liver function.

PMID- 12186410
TI  - N-acetyltransferase 2 genotype-related sulfapyridine acetylation and its adverse
      events.
AB  - Sulfapyridine (SP), one of the metabolites of sulfasalazine (SASP), is further
      metabolized into N-acetylsulfapyridine (AcSP) by polymorphic N-acetyltransferase
      2 (NAT2). NAT2 activity has been diagnosed by phenotyping, that is, evaluating
      plasma concentrations or urinary excretions of tentatively administered test
      drugs for dose individualization and avoidance of serious adverse events. Herein,
      we investigated the relationship between NAT2 genotypes and the pharmacokinetics
      of SP in healthy Japanese subjects, as well as the adverse events of SASP in
      patients with inflammatory bowel disease (IBD). Eight healthy subjects and 13 IBD
      patients were classified into three groups by NAT2 genotyping; the homozygote for
      the wild-type allele (Rapid Types), the compound heterozygote for the wild-type
      and mutant alleles (Intermediate Types), and the homozygote for mutant alleles
      (Slow Types). A single oral dose of 40 mg/kg SASP was administered to each
      healthy subject, and plasma and urine samples were taken until 51 and 72 h after
      administration, respectively. Both the SP and AcSP concentrations in each sample
      were determined by the HPLC method. The NAT2 genotypes were well-correlated with
      the plasma concentrations or urinary excretions of SP and AcSP in 8 healthy
      subjects, except for one Slow Type. In patients with IBD, skin rash was seen in 3
      of 6 Rapid Types and 1 of 6 Intermediate Types, consistent with the concept that
      hypersensitive reactions are independent of serum SP concentrations. In contrast,
      SASP dosing-related acute pancreatitis was found in the Slow Type patient. In
      this case, the NAT2 activity was diagnosed by genotyping in advance, and the
      medical staff could pay scrupulous attention, resulting in no serious subjective
      symptoms such as abdominal pain, anorexia or fever. Further investigations on the
      relationship between the NAT2 genotype and adverse events are required, although
      genotyping appeared to be a promising method to avoid such serious adverse
      events.

PMID- 12186411
TI  - Effects of SK-896, a new human motilin analogue ([Leu13]motilin-Hse), on
      postoperative ileus in dogs after laparotomy.
AB  - The effects of SK-896, a new human motilin analogue ([Leu13]motilin-Hse), on
      digestive tract motility in postoperative ileus were evaluated in a dog model of
      ileus after laparotomy. SK-896 was intravenously administered at 0.17, 0.33 and
      0.67 microg/kg starting soon after operation and then at 6-h intervals, for a
      total of 9 times. SK-896 progressively, dose-dependently and significantly
      increased the duodenal motility from 1 h after operation. The recovery time of
      the gastrointestinal-interdigestive migrating complex (GI-IMC) activity, which is
      an indicator of normal gastrointestinal tract activity after laparotomy, was 56.5
      +/- 5.0 h in the control group. SK-896 significantly shortened this recovery
      time. On the other hand, the plasma SK-896 concentrations declined
      diexponentially after administration, and can be described by a linear
      pharmacokinetic model within the dose range used. In addition, the
      pharmacokinetics of SK-896 did not change significantly at any postoperative
      time. There was no correlation between the plasma SK-896 concentrations and the
      intensity of duodenal motility, because the activity in the duodenum decreased
      transiently 13 h after laparotomy and increased with time thereafter. The changes
      in the activity are considered to reflect the progressive changes in the state of
      ileus. In conclusion, SK-896 increased the duodenal motility significantly,
      shortening the recovery time of GI-IMC-like activity in dogs with post-laparotomy
      ileus. Therefore, it is expected from these results that SK-896 would be useful
      and effective for the treatment of gastroparalysis after abdominal surgery.

PMID- 12186412
TI  - Biodistribution and pharmacokinetics of O-palmitoyl tilisolol, a lipophilic
      prodrug of tilisolol, after intravenous administration in rats.
AB  - The purpose of this study was to modify the biodistribution and pharmacokinetics
      of tilisolol, a beta-blocker, using the palmitoyl prodrug approach. After
      intravenous administration of tilisolol and O-palmitoyl tilisolol in rats, drug
      concentrations were determined in blood, bile, urine, and several tissues. The
      concentration-time profiles of tilisolol and O-palmitoyl tilisolol were analyzed
      pharmacokinetically. The blood concentrations of O-palmitoyl tilisolol after
      intravenous administration of O-palmitoyl tilisolol were about 10-fold higher
      than those of tilisolol after intravenous administration of tilisolol. The
      biliary excretion rates of O-palmitoyl tilisolol and tilisolol after intravenous
      administration of O-palmitoyl tilisolol were about 10- to 100-fold larger than
      those of tilisolol after intravenous administration of tilisolol. In addition,
      the hepatic uptake clearance of O-palmitoyl tilisolol after intravenous
      administration of O-palmitoyl tilisolol was 3.6-fold higher than that of
      tilisolol after the intravenous administration of tilisolol. In the in vitro
      experiments, it was demonstrated that the distribution ratios between blood cells
      and plasma (blood/plasma) of O-palmitoyl tilisolol and tilisolol was 95.7 and
      55.5%, respectively. These findings suggest that O-palmitoyl tilisolol exists as
      a binding form with biological components, especially blood cells, in systemic
      circulation. In conclusion, the palmitoyl prodrug approach is useful as a drug
      delivery system to deliver the parent drug to the liver.

PMID- 12186413
TI  - Effect of experimental renal failure on the pharmacokinetics of losartan in rats.
AB  - The purpose of this investigation was to determine whether the pharmacokinetics
      of the angiotensin II receptor antagonist losartan is altered in renal failure.
      Male Wistar rats were pretreated with uranyl nitrate or subjected to bilateral
      ureteral ligation to produce acute renal failure (ARF). Saline-injected and sham
      operated rats, respectively, served as controls. Uranyl nitrate-treated rats
      showed significantly higher serum concentrations of losartan after oral
      administration and the area under the serum concentration-time curve (AUC(0-24))
      of losartan increased about 3-fold compared to control rats. The systemic
      clearance of losartan significantly decreased from 410 +/- 254ml/h/kg in control
      to 177 +/- 112ml/h/kg in uranyl nitrate-treated rats. In order to investigate the
      mechanisms of reduced clearance of losartan associated with ARF, a hepatic
      microsome fraction was prepared from normal and ARF rats. No significant
      difference was found in the metabolism of losartan by hepatic microsomes prepared
      from ARF and control rats. In addition, the metabolic activity of microsomes was
      examined in the presence of uremic rat serum. The unbound clearance of losartan
      and the unbound clearance associated with the formation of EXP3174 in the
      presence of uremic serum were significantly lower than those in the presence of
      control serum. Furthermore, the metabolism of losartan was inhibited by indoxyl
      sulfate, a uremic toxin, in an uncompetitive manner. These results suggest that
      ARF is associated with reduced clearance of losartan due to the inhibition of
      hepatic metabolism by accumulated uremic toxin(s).

PMID- 12186414
TI  - Comparative study on salivary distribution of fluoroquinolones in rats.
AB  - As a basic approach to identifying the distribution mechanism of quinolone
      antibiotics into saliva, salivary excretion of five fluoroquinolones,
      ciprofloxacin (CPFX), norfloxacin (NFLX), lomefloxacin (LFLX), ofloxacin (OFLX)
      and sparfloxacin (SPFX), was compared in rats. Blood, parotid and mandibular
      saliva were periodically collected from the anesthetized rats after bolus i.v.
      administration (10 mg/kg) of the quinolones. Quantification of the
      fluoroquinolones was performed by HPLC methods. The saliva-to-plasma unbound
      concentration (S/Pu) ratios of the fluoroquinolones in parotid saliva were larger
      than those of mandibular saliva. These five quinolones had considerably different
      S/Pu ratios from 0.014 to 1.497, while the S/Pu ratios theoretically calculated
      by the pH-partition theory were around 1.0 to 1.3, which showed no relationship
      to the corresponding measured ratios. Satisfactory linear correlations were
      observed in the plots of measured S/Pu ratios against 1-octanol-water partition
      coefficients of the fluoroquinolones in both types of saliva. These results
      indicate that fluoroquinolones possess different diffusibility in salivary
      distribution among the drugs and between parotid and mandibular glands. It was
      also clarified that the lipophilicity of the fluoroquinolones primarily
      determines the extent of salivary excretion.

PMID- 12186415
TI  - Effect of docosahexaenoic acid-fortified Chlorella vulgaris strain CK22 on the
      radial maze performance in aged mice.
AB  - Effect of docosahexaenoic acid (DHA) [22: 6(n-3)]-fortified Chlorella oil
      fraction on radial maze performance was studied in aged mice. Male ICR mice aged
      9 months were fed a diet containing 2 g DHA-fortified Chlorella oil fraction/100
      g diet or normal diet (Control group) for 2 months. Two months after the start of
      feeding, the mice were tested for learning ability related to 2 types of memory,
      reference memory and working memory, with the partially (4 of 8) baited eight-arm
      radial maze. Reference memory is a kind of information that should be retained
      until the next trial. Working memory is a kind of information that disappears in
      a short time. Entry into the unbaited arms and repeated entry into the visited
      arms were defined as reference memory errors and working memory errors,
      respectively. DHA-fortified Chlorella oil fraction administration to mice for 2
      months resulted in a significant decrease in the number of working memory errors
      without affecting the number of reference memory errors. A significant increase
      in the DHA content in the brain was also observed. These results suggest that the
      intake of DHA-fortified Chlorella oil fraction effectively enhances working
      memory in maze performance.

PMID- 12186416
TI  - Flavonoids suppress the cytotoxicity of linoleic acid hydroperoxide toward PC12
      cells.
AB  - The suppressive effect of flavonoids on the cytotoxicity of linoleic acid
      hydroperoxide (LOOH) toward rat phenochromocytoma PC12 cells was examined. The
      extent of cytotoxicity was shown on the basis of % survival determined by the
      trypan blue exclusion test. On preincubation of cells with either 3
      hydroxyflavone, quercetin, or luteolin prior to LOOH exposure, the cytotoxicity
      was considerably suppressed. In contrast, on coincubation of cells with either
      eriodictyol, quercetin, kaempherol, luteolin, or 3-hydroxyflavone and LOOH, it
      was markedly suppressed. Regardless of incubation conditions, quercetin, 3
      hydroxyflavone, and luteolin were thus more effective as protective agents
      against the cytotoxicity than the other flavonoids. These flavonoids further
      showed a suppressive effect on coincubation rather than on preincubation. These
      results suggest that such flavonoids are beneficial for cells under oxidative
      stress.

PMID- 12186417
TI  - Indenopyridine hydrochloride induced testicular spermatogenesis failure with high
      seminal alkaline phosphatase levels in male dog.
AB  - Indenopyridine hydrochloride (IH), an antispermatogenic agent, was tested to
      determine the testicular pathological changes, seminal spermatozoa concentrations
      and seminal plasma alkaline phosphatase levels in male dogs. A single oral dosage
      of 30 mg IH/kg BW induced the dissociation and premature release of germ cells
      into the lumens of seminiferous tubules. Ring-shaped spermatid nuclei, nuclear
      pykonosis of spermatocytes and multinucleated cell associations were also
      observed. Thereafter, the spermatogenic index (SI) significantly decreased one
      day after IH administration. Moreover, seminal spermatozoa concentrations
      decreased two weeks after drug treatment; and there was a statistically
      significant difference in spermatozoa production inhibited by IH compared to the
      control. Reversible spermatogenesis was noted 7 weeks after IH treatment in male
      dogs. Meanwhile, seminal plasma alkaline phosphatase levels also significantly
      increased two weeks after IH treatment. These data confirm that IH might induce a
      two-month inhibition of spermatogenesis in male dogs.

PMID- 12186418
TI  - Neuroprotective effects of constituents of the oriental crude drugs, Rhodiola
      sacra, R. sachalinensis and Tokaku-joki-to, against beta-amyloid toxicity,
      oxidative stress and apoptosis.
AB  - We tested the constituents of two Rhodiola plants, Rhodiola sacra S. H. Fu and R.
      sachalinensis A. BOR, and an Oriental crude drug, Tokaku-joki-to, for their
      neuroprotective effects. Of the 58 compounds tested, six had considerable
      protective effects against beta-amyloid-induced death of B103 neuronal cells in
      vitro. These six compounds also showed protective effects against staurosporine
      induced cell death, and two of the six compounds protected neurons from H2O2
      induced cell death. These results suggest that some of the tested compounds
      protect neurons from beta-amyloid toxicity based on antiapoptotic and
      antioxidative activity.

PMID- 12186419
TI  - Effects of oleanane-type triterpenoids from fabaceous plants on the expression of
      ICAM-1.
AB  - We examined the inhibitory effects of oleanane-type triterpenoids from fabaceous
      plants on the TNF-alpha-induced expression of cell adhesion molecules on THP-1
      human monocytic leukemia cells and compared them with a glucocorticoid
      dexamethasone. In a cell-based ELISA, abrisapogenol E, soyasapogenols B and C,
      soyasapogenol B, kuzusapogenol B-methyl ester, and oleanolic acid significantly
      inhibited intercellular adhesion molecule (ICAM-1) expression. Moreover, these
      triterpenoids showed the same activity as dexamethasone. On the other hand, the
      absence of hydroxyl group at C-24 position of sapogenin rather to increase ICAM-1
      expression compared with the untreated control. We concluded that the activity of
      oleanane saponins and sapogenins against ICAM-1 expression are dependent upon the
      position of the hydroxyl group, and in particular upon the status of the C-21 and
      C-24 positions and of the glycosyl group at C-3 position.

PMID- 12186420
TI  - Survey of the influence of Chinese medicinal prescriptions on amylase activity in
      mouse plasma and gastrointestinal tube.
AB  - Chinese medicinal prescriptions were screened for their effects on alpha-amylase
      activity in mouse plasma. Daio-kanzo-to, Hange-koboku-to, Saiko-ka-ryukotsu-borei
      to, Saiko-keishi-kankyo-to and Mao-to changed the activity in isolated mouse
      plasma greatly and concentration dependently. However, no prescription influenced
      the elevation of postprandial blood glucose.

PMID- 12186421
TI  - Effect of probucol on cytochrome P450 activities in human liver microsomes.
AB  - The effects of probucol, a cholesterol-lowering agent, on several cytochrome P450
      (CYP) isoform-specific reactions in human liver microsomes were investigated to
      predict drug interactions with probucol in vivo from in vitro data. The following
      eight CYP catalytic reactions were used in this study: CYP1A1/2-mediated 7
      ethoxyresorufin O-deethylation, CYP2A6-mediated coumarin 7-hydroxylation, CYP2B6
      mediated 7-benzyloxyresorufin O-debenzylation, CYP2C8/9-mediated tolbutamide
      methylhydroxylation, CYP2C19-mediated S-mephenytoin 4'-hydroxylation, CYP2D6
      mediated bufuralol 1'-hydroxylation, CYP2E1-mediated chlorzoxazone 6
      hydroxylation, and CYP3A4-mediated testosterone 6beta-hydroxylation. Probucol had
      neither stimulatory nor inhibitory effects on CYP1Al/2, 2A6, 2B6, 2C8/9, 2C19,
      2D6, 2E1, and 3A4 activities at concentrations up to 300 microM, indicating that
      probucol, at the expected therapeutic concentrations, would not be predicted to
      cause clinically significant interactions with other CYP-metabolized drugs.

PMID- 12186422
TI  - In vivo analysis of glucocorticoid-induced reporter gene expression using gene
      gun DNA delivery.
AB  - Glucocorticoid regulates various physiological processes via the activation and
      repression of gene expression. The anti-inflammatory effects and the adverse
      effects are believed to be dependent on the repression and the activation of
      genes, respectively. Reporter gene assay is a useful technique to separately
      evaluate these two functions and has been used for in vitro screening of novel
      ligands for the glucocorticoid receptor (GR). We report here the application of a
      reporter gene assay for the in vivo determination of the GR-mediated gene
      activation. A reporter plasmid containing glucocorticoid response elements was
      introduced to abdominal mouse skin using a gene gun. Administration of
      prednisolone induced the expression of the reporter gene, only when the GR
      expression plasmid was co-transfected with the reporter plasmid. Endogenous
      levels of corticosterone appeared to be negligible in this protocol. The dose
      response for this induction was comparable to those for the decreases in thymus
      weight and serum corticosterone. These results suggest that gene gun-mediated
      skin transfection enables the in vivo reporter gene assay and that this technique
      can be used to predict the potency of ligands for the GR-mediated gene
      activation.

PMID- 12186423
TI  - False positive blood tacrolimus concentration in microparticle enzyme
      immunoassay.
AB  - The difference in the blood concentration of tacrolimus between the assay
      methods, microparticle enzyme immunoassay (MEIA) and enzyme linked immunosorbent
      assay (ELISA) was observed in a liver transplant recipient with anemia. MEIA
      provided significantly higher concentration than those of ELISA (7.8+/-1.9 vs.
      5.0 +/- 1.8nglml, p<0.05) while the patient had low haematocrit <25%. The
      difference, however, was not observed during the periods with haematocrit >25%.
      This observation suggested that unknown tacrolimus levels generated from
      difference in assay methods gave incorrect blood tacrolimus during anemia. False
      positive concentration of tacrolimus ranging 0.1-3.3 ng/ml was observed in MEIA
      applying to the blood samples obtained from the patients without receiving
      tacrolimus. The false positive tacrolimus increased in the samples with lower
      hematocrit, suggesting that MEIA gave incorrect blood tacrolimus during anemia.
      Since MEIA potentially overestimates the tacrolimus levels, ELISA should be used
      for blood tacrolimus monitoring in the patients with anemia.

PMID- 12186424
TI  - Regulating factors for microglial activation.
AB  - Microglia, residential macrophages in the central nervous system, can release a
      variety of factors including cytokines, chemokines, etc. to regulate the
      communication among neuronal and other types of glial cells. Microglia play
      immunological roles in mechanisms underlying the phagocytosis of invading
      microorganisms and removal of dead or damaged cells. When microglia are
      hyperactivated due to a certain pathological imbalance, they may cause neuronal
      degeneration. Pathological activation of microglia has been reported in a wide
      range of conditions such as cerebral ischemia, Alzheimer's disease, prion
      diseases, multiple sclerosis, AIDS dementia, and others. Nearly 5000 papers on
      microglia can be retrieved on the Web site PubMed at present (November 2001) and
      half of them were published within the past 5 years. Although it is not possible
      to read each paper in detail, as many factors as possible affecting microglial
      functions in in vitro culture systems are presented in this review. The factors
      are separated into "activators" and "inhibitors," although it is difficult to
      classify many of them. An overview on these factors may help in the development
      of a new strategy for the treatment of various neurodegenerative diseases.

PMID- 12186425
TI  - Development of an enzyme-linked immunosorbent assay for the quantification of
      amiodarone.
AB  - A sensitive and specific enzyme-linked immunosorbent assay for an antiarrhythmic
      drug, amiodarone (AMI), was developed, which is capable of measuring levels as
      low as 16 ng/ml. Anti-AMI antibody was obtained by immunizing rabbits with an
      antigen conjugated with bovine serum albumin using diazotized 4-amino-1-(2
      diethylaminoethoxy)-2,6-diiodobenzene. Enzyme labeling of AMI with beta-D
      galactosidase was similarly performed using a diazotized 4-amino-1-(2
      diethylaminoethoxy)-2,6-diiodobenzene. This enzyme-linked immunosorbent assay was
      specific for AMI and showed a very slight cross-reactivity (1.25%) with its major
      metabolite, mono-N-desethylamiodarone. The values of the AMI concentrations
      measured by this assay were in good correlation to those by HPLC. Its analytical
      applicability was demonstrated by a kinetic study with human liver microsomes.
      The enzyme-linked immunosorbent assay should be a valuable tool in therapeutic
      drug monitoring and pharmacokinetic studies of AMI.

PMID- 12186426
TI  - Round shape enlargement of the yeast spheroplast of Saccharomyces cerevisiae by
      HM-1 toxin.
AB  - The effects of HM-1 killer toxin (HM-1) on yeast spheroplasts of Saccharomyces
      cerevisiae were examined under osmotically stabilized conditions. Prolonged
      incubation of spheroplasts in nutrient-rich media resulted in an increase in
      volume, accompanied by aberrant morphological changes. By contrast, spheroplasts
      were enlarged, maintaining a round shape, when incubated in HM-1 media. The
      required 50% effective dose of HM-1 was as low as 2.2 x 10(-8) M, and this effect
      by HM-1 was specific to yeast sensitive to RM-1. Some parts of the enlarged
      spheroplasts were stable, but the round shape was deformed as HM-1 was removed
      from the medium. In both the control and HM-1-treated spheroplasts, the total
      protein and DNA content were increased by approximately three and four times in
      response to their incubations, respectively. Cytochemical analysis by 4'6
      diamidino-2-phenylindol (DAPI) staining showed multiple nuclei. Consistently,
      actin patches of cells were evenly distributed in both the control and HM-1
      treated spheroplasts. A similar enlargement of spheroplasts was observed with
      lipophilic antifungal compounds, aculeacin A and papulacandin B, but the effects
      were distinct from those of HM-1 because the spheroplasts resulted in lysis after
      a long incubation. The molecular mechanism(s) behind this unique observation
      remains to be studied, but it is clear that HM-1 is an excellent tool for
      studying yeast cell biology.

PMID- 12186427
TI  - Effects of gentamicin sulfate on enzyme activities of carbonic anhydrase from
      human erythrocytes in vitro and from rat erythrocytes in vivo.
AB  - The effects of gentamicin sulfate on carbonic anhydrase (CA) enzyme activity in
      in vitro human and in in vivo rat erythrocytes were investigated. For in vitro
      study, human carbonic anhydrase-I and -II (HCA-I and HCA-II) were purified by
      affinity-column chromatography, and rats were used for in vivo study. In vivo and
      in vitro CA enzyme activity was determined colorimetrically using the CO2
      hydration method of Wilbur and Anderson as modified by Rickli et al. Gentamicin
      sulfate (1.98-9.90 mM) showed in vitro inhibitory effects on HCA-I and HCA-II
      hydratase activity up to a 2 mM concentration, when determined using the C02
      hydratase method. Rat erythrocyte CA activity was significantly inhibited for up
      to 3 h (p<0.001) following intramuscular administration of gentamicin sulfate to
      Sprague-Dawley rats (3.2 mg/kg body weight). In conclusion, gentamicin sulfate
      inhibits CA enzyme activity in vivo and at low concentrations in vitro, but
      activated it at high concentrations (> or = 4 mM) in vitro.

PMID- 12186429
TI  - PCR-based sensitive detection of medicinal fungi Hericium species from ribosomal
      internal transcribed spacer (ITS) sequences.
AB  - Based on phylogenetic analysis of rDNA internal transcribed spacer (ITS)
      sequences, a pair of specific primers were designed for differentiating the
      Chinese traditional medicine Hericium species from other mushrooms by PCR. PCR
      was performed, with total DNAs as a template at an annealing temperature of 52-57
      degrees C. Positive amplification was obtained from H. erinaceus with all DNA
      templates from different resources, but not from other related species. The
      result indicated that H. erinaceus could be clearly distinguished from other
      fungi by detection PCR, and no incorrect discrimination was found under the same
      reaction conditions. The primers were also successfully employed to identify H.
      erinaceus with different tissue types.

PMID- 12186428
TI  - Functional analysis of zinc finger proteins that bind to the silencer element in
      the glutathione transferase P gene.
AB  - Glutathione transferase P (GST-P) gene expression is repressed in normal rats but
      markedly promoted during the early stage of chemical hepatocarcinogenesis. We
      have previously identified a silencer region in this gene promoter. The silencer
      is composed of several cis-elements to which at least three proteins (Silencer
      factor-A, -B, and -C: SF-A, SF-B, and SF-C) are known to bind. We cloned and
      characterized the nuclear factor 1 family and the CCAAT/enhancer-binding protein
      family as SF-A and SF-B, respectively. Recently, zinc finger proteins as
      candidates for SF-C, which binds to GST-P silencer 2 (GPS2), were isolated. These
      proteins include four Kruppel-like proteins (BTEB2, EZF, LKLF, and TIEG1) and
      other factors containing multiple zinc finger motifs (TFIIIA and MZFP). In the
      present study, we found that the zinc finger proteins showed the same DNA-binding
      affinities to GPS2. Moreover, transfection analyses revealed that BTEB2, EZF, and
      TIEGI repressed the GST-P promoter activity. Therefore, these three factors might
      contribute to the repression of the GST-P gene expression in normal rat liver.

PMID- 12186430
TI  - Biological activity of 4-acetyltropolone, the minor component of Thujopsis
      dolabrata SIeb. et Zucc. hondai Mak.
AB  - 4-Acetyltropolone, a minor component of Thujopsis dolabrata SIEB. et Zucc. hondai
      MAKINO, showed antimicrobial activity against various microorganisms including
      wood-rotting fungi, a phytogrowth-inhibitory effect with chlorophyll biosynthesis
      inhibition, cytotoxic effect and inhibitory activity on metalloproteases. This
      compound had strong antifungal activity on Daedalea dickinsii IFO-4979 [minimum
      inhibitory concentration (MIC): 0.2 microg/ml] and Coriolus versicolor IFO-4940
      (MIC: 0.39 microg/ml). Its cytotoxic effect at 20.0/microg/ml on human stomach
      cancer KATO-III and Ehrich's ascites carcinoma was stronger than those of
      podophyllotoxin, vincristine and vinblastine, the anticancer agents isolated from
      higher plants and used clinically. This compound also had potent antibacterial
      activity against Staphylococcus epidermidis IFO-12993, its MIC being 1.56
      microg/ml. However, other biological activities of 4-acetyltropolone were lower
      than those of hinokitiol which is the main component of this plant, suggesting
      that the contribution of the acetyl group at C-4 to biological activity is
      smaller than that of the isopropyl group at that position. The acute toxicity of
      4-acetyltropolone (LD50: 335.2 mg/kg) to mice was much lower than that of
      hinokitiol (LD50: 191 mg/kg).

PMID- 12186431
TI  - New rapid enzyme-linked immunosorbent assay to detect antibodies against
      bacterial surface antigens using filtration plates.
AB  - An easy and rapid ELISA system, Filtration ELISA, to detect antibodies against
      bacterial cell surface antigens was developed using a 96-well filtration plate
      fitted with a 0.22microm membrane (MultiScreen-GV, Millipore). Bacterial whole
      cells were used as antigens without fixing the cells with formalin etc. The whole
      cell antigens were washed by vacuum filtration through a filter and resuspended
      in washing buffer. Assay reactions could be done in the wells without losing the
      solution. The technique was established using antisera of mice immunized with
      Escherichia coli, and then evaluated by assaying antibodies to Shiga-toxin
      producing E. coli O157:H7 (STEC), Staphylococcus aureus and Lactobacillus
      acidophilus in fecal extracts of 157 children who had eaten school lunches
      contaminated with STEC in comparison with 25 age-matched control children. The
      lunch group showed significantly higher IgA antibody titers against STEC than the
      control group (p<0.0005), but not against L. acidphilus. The results indicate
      that Filtration ELISA is a quantitative and specific technique for measuring
      antibodies against antigens on the surface of bacteria without extracting
      antigens from the bacteria. This technique is widely applicable to the assay of
      antibodies in various samples including serum and fecal extract against various
      kinds of bacteria.

PMID- 12186432
TI  - Detection of chimeric genes in Ewing's sarcoma and its clinical applications.
AB  - Ewing's sarcoma (ES), most commonly an undifferentiated tumor of bone, belongs to
      the enigmatic diagnostic category of small round cell tumors (SRCT) of childhood.
      The consistent presence of the translocation t (11; 22) in the vast majority of
      tumors provides evidence for a common histogenesis in ES and its family of tumors
      (ESFT), and also provides a unique diagnostic characteristic to discriminate this
      tumor family from SRCT. Molecular analysis of this translocation has revealed
      that it forms a chimeric gene between EWS on chromosome 22 and FLI-1 on
      chromosome 11. Similarly, the variant t (21; 22), t (7; 22), t (17; 22), and t
      (2; 22) rearrangements also form chimeric genes between regions of EWS and the
      ETS gene family (ERG, ETV1, E1AF, and FEV). Detection of these specific chimeric
      genes would provide a method for diagnosis of ESFT. We have developed a procedure
      for simultaneous detection of the chimeric genes by reverse transcription
      polymerase chain reaction (RT-PCR) with a mixture of primers. We conclude that
      the detecting those chimeric genes by this method can be easy and useful for
      diagnosis of ESFT. Moreover, by defining the specific chimeric gene it is
      possible to detect the tumor cell contamination in autologous blood stem cell
      transplantation.

PMID- 12186433
TI  - Platonin, a photosensitizing dye, improves circulatory failure and mortality in
      rat models of endotoxemia.
AB  - Platonin, a cyanine photosensitizing dye, is a potent macrophage-activating agent
      and an immunomodulator. In this study, we compare the inhibitory effects of
      platonin with those of the three clinical drugs minocycline, clindamycin, and
      cyclosporin, on hypotension, tachycardia, and nitric oxide (NO) formation in a
      rat model of circulatory shock induced by Escherichia coli lipopolysaccharide
      (LPS). We also evaluate the effect of drugs on the 6 h survival rate in LPS
      treated rats. Administration of LPS (15 mg/kg) caused a rapid drop in mean
      arterial blood pressure (MAP). Minocycline (10 mg/kg, i.v.) significantly
      prevented the fall of MAP at 3 h, and platonin (100 microg/kg, i.v.) markedly
      prevented the fall of MAP within the 0-3 h period after LPS administration.
      However, neither clindamycin (10 mg/kg, i.v.) nor cyclosporin (15 mg/kg, i.v.)
      had any effects in this study. On the other hand, an inducible NO synthase
      inhibitor, NG-nitro-L-arginine ester (L-NAME), caused a significantly increase in
      MAP and a moderate bradycardia after LPS administration. In addition, an increase
      in plasma nitrate formation elicited by endotoxemia was significantly reduced by
      pretreatment with either minocycline (10 mg/kg) or platonin (100 microg/kg).
      However, only platonin (100 microg/kg) markedly reduced the mortality and
      prolonged the mean survival time in LPS-treated rats. Minocycline, clindamycin,
      and cyclosporin had no effects under the same conditions. Further studies using
      an electron spin resonance (ESR) method were conducted on the scavenging activity
      of platonin on the free radicals formed. Platonin (10 microm) greatly reduced the
      ESR signal intensity of superoxide anion, hydroxyl radical, and methyl radical
      formation. In conclusion, platonin has beneficial effects on ameliorating
      endotoxaemia. This protective effect of platonin may be mediated, at least
      partly, by the reduced drop in MAP and the inhibition of NO and free radical
      formation in rat models of endotoxemia.

PMID- 12186434
TI  - Intraoperative MR imaging: can image guidance improve therapy?

PMID- 12186435
TI  - Effect of radiologic contrast media on cell volume regulatory mechanisms in human
      red blood cells.
AB  - RATIONALE AND OBJECTIVES: The authors performed this study to evaluate cell
      volume regulation in human red blood cells (RBCs) after incubation in solutions
      of three contrast media: iohexol (830 mOsm), ioxaglate (520 mOsm), and iodixanol
      (300 mOsm). MATERIALS AND METHODS: Whole blood sampled from six healthy subjects
      was exposed to Ringer solutions containing 25% or 5% vol/vol iohexol (final
      osmolality, 440 or 340 mOsm, respectively), ioxaglate (final osmolality, 395 or
      335 mOsm, respectively), iodixanol (final osmolality, 330 or 315 mOsm,
      respectively), or NaCl (control solutions with the same osmolality as that of the
      contrast media). In some experiments, control RBCs were subjected to a hyposmotic
      solution (100 mOsm). RBC volumes were obtained with a Coulter counter. RESULTS:
      The RBCs showed normal regulatory cell shrinkage after hyposmotically induced
      swelling. All 25% vol/vol contrast material solutions and their control solutions
      induced RBC shrinkage (range, 6% +/- 1 [standard error] to 22% +/- 3). The same
      was true for cells exposed to 5% vol/vol contrast material (range, 4% +/- 1 to 7%
      +/- 1). The shrinkage phase was followed by cell swelling (10% +/- 2 to 20% +/- 2
      for 25% contrast material and their control solutions and 8% +/- 1 to 15% +/- 2
      for 5% contrast material and their control solutions). No contrast material
      exposed RBCs increased their volumes to the level reached with their control
      solutions. CONCLUSION: RBCs exposed to hyperosmotic iohexol, ioxaglate, or
      iodixanol solutions shrank and then swelled. The degree of shrinkage and
      subsequent swelling could not be explained simply with the osmolality of the test
      solutions. Physicochemical properties of the contrast media must be involved,
      putatively affecting electrolyte fluxes over the RBC membrane. Possible targets
      of these effects are the K+/Cl- symporter, K+ channels, and the Na+/K+/Cl-
      symporter.

PMID- 12186436
TI  - Initial results of the effects of diuresis on gadolinium enhancement in MR
      imaging of the abdomen.
AB  - RATIONALE AND OBJECTIVES: The authors performed this study to assess the effects
      of furosemide-induced diuresis on paramagnetic contrast material enhancement at
      magnetic resonance (MR) imaging of the kidney, liver, spleen, and psoas muscle.
      MATERIALS AND METHODS: Twenty-five patients (average age, 44.9 years; age range,
      23-74 years; 13 men, 12 women) who were suspected of having unilateral renal
      hydronephrosis received 0.1 mmol/kg contrast material with a standardized
      injection and imaging protocol to assess organ signal intensity at 0-5 minutes
      after injection. All patients had a normal serum creatinine level. Imaging was
      performed with a 1.5-T magnet by using a fat-suppressed fast spoiled gradient
      echo pulse sequence and a 70 degrees flip angle. Eight patients received 40 mg of
      furosemide 10 minutes before contrast material injection. RESULTS: The areas of
      the renal cortical and medullary signal intensity curves minus baseline in the
      unilateral normal kidneys were significantly greater in the group who received
      furosemide (P = .026 and P = .037, respectively). The areas of the renal cortical
      and medullary signal intensity minus baseline in the unilateral hydronephrotic
      kidneys were also significantly greater in the group that received furosemide (P
      = .036 and P = .026, respectively). There was a statistically significant
      increase in splenic enhancement (P = .02) and a tendency for increased liver (P =
      .09) and psoas muscle (P = .08) enhancement. CONCLUSION: Furosemide-induced
      diuresis appears to potentiate the cortical and medullary MR renogram, as well as
      the MR splenogram. A rapid shift in water compartmentalization from the
      intracellular to the extracellular space and increased renal water content with
      diuresis are possible explanations.

PMID- 12186437
TI  - Decreasing rate of fatty involution at screening mammography.
AB  - RATIONALE AND OBJECTIVES: This study was performed to document the perceived
      decrease in fatty involution at screening mammography during the past decade and
      evaluate the influence of hormone replacement therapy (HRT). MATERIALS AND
      METHODS: In December 1996, the mammograms of 261 consecutive screening patients
      with a comparison study obtained 5 years earlier were evaluated, and their
      breasts were categorized according to Breast Imaging Reporting and Data System
      categories for breast density. The women, aged 50-59 years, included 119 who had
      been receiving HRT for 0.25-15 years (mean, 3 years). From the files, 261 age
      matched screening mammograms from 1986 were obtained; these patients also had
      comparison mammograms from 1981. Analysis of variance was used to determine
      differences between the 1980s group, the 1990s group receiving HRT, and the 1990s
      group not receiving HRT. Scheffe tests were used for post hoc comparisons.
      Stepwise regression analysis was used to evaluate the relative influence of age,
      decade, score of the first mammogram, and HRT. RESULTS: Breast density for the
      1991 mammograms did not differ significantly from that in 1981 (P < .05). Initial
      breast density was the best predictor of final breast density in both decades (P
      < .001), regardless of HRT status. The change in breast density (toward fatty)
      over the 5-year interval in the 1980s (mean, 0.48) was significantly greater than
      that in both 1990s groups (mean for HRT group, 0.11; no HRT, 0.30; P < .05).
      CONCLUSION: These results confirm that breast density at screening mammography in
      the 1990s did not decrease with age at the same rate as in the 1980s, even in
      patients not receiving HRT.

PMID- 12186438
TI  - Computerized assessment of tissue composition on digitized mammograms.
AB  - RATIONALE AND OBJECTIVES: The authors developed a computerized method for the
      quantitative assessment of breast tissue composition on digitized mammograms.
      MATERIALS AND METHODS: Three radiologists were asked to review 200 digitized
      mammograms and independently provide a Breast Imaging Reporting and Data System
      like rating for breast tissue composition on a scale of 0 to 4. These values were
      incorporated into a "consensus" rating that was used as a reference point in the
      development and evaluation of a computerized method. After tissue segmentation
      that excluded nontissue areas, a set of quantitative features was computed. A
      computerized summary index that attempts to reproduce the radiologists' ratings
      was developed. Correlation coefficients (Pearson r) were used to compare the
      computerized index with the consensus ratings. RESULTS: Some individual features
      computed for the relatively dense breast areas showed good correlation (r > 0.8)
      with the radiologists' subjective ratings. The summary index of tissue
      composition demonstrated a significant correlation (r = 0.87), as well.
      CONCLUSION: Computerized methods that show good correlation with radiologists'
      ratings of breast tissue composition can be developed.

PMID- 12186439
TI  - Quantitative MR imaging assessment of prostate gland deformation before and
      during MR imaging-guided brachytherapy.
AB  - RATIONALE AND OBJECTIVES: The authors performed this study to document the
      deformations that occur between pretreatment magnetic resonance (MR) imaging and
      intraoperative MR imaging during brachytherapy. MATERIALS AND METHODS: MR images
      obtained at 1.5 and 0.5 T in 10 patients with prostate cancer were analyzed for
      changes in the shape and substructure of the prostate. Three-dimensional models
      of the prostate were obtained. The authors measured anteroposterior dimension;
      total gland, peripheral zone, and central gland volumes; transverse dimension;
      and superoinferior height. RESULTS: Gland deformations were seen at visual
      inspection of the three-dimensional models. The anteroposterior dimension of the
      total gland, central gland, and peripheral zone increased from 1.5- to 0.5-T
      imaging (median dimension, 4.9, 1.5, and 1.8 mm, respectively), and the increase
      was greatest in the peripheral zone (P < .05, all comparisons). There was a
      decrease in the transverse dimension from 1.5- to 0.5-T imaging (median, 4.5 mm;
      P < .005). The total gland volume and the superoinferior height did not show a
      statistically significant change. CONCLUSION: There were significant deformations
      in the shape of the prostate, especially in the peripheral zone, between the two
      imaging studies. The likely causes of the shape change are differences in rectal
      filling (endorectal coil used in 1.5-T studies vs obturator in 0.5-T studies)
      and/or changes in patient position (supine vs lithotomy). These findings suggest
      that pretreatment images alone may not be reliable for accurate therapy planning.
      It may be useful to integrate pre-and intraoperative data.

PMID- 12186440
TI  - Use of serial FDG PET to measure the response of bone-dominant breast cancer to
      therapy.
AB  - RATIONALE AND OBJECTIVES: The authors performed this study to determine the
      feasibility of using quantitative 2-[fluorine-18]fluoro-2-deoxy-D-glucose (FDG)
      positron emission tomography (PET) to monitor the response of breast cancer bone
      metastases to therapy. MATERIALS AND METHODS: Twenty-four women with stage IV
      bone-dominant breast carcinoma were included in this study. Whole-body FDG PET
      imaging was performed at serial time points during the course of therapy. FDG PET
      scans were interpreted quantitatively by using the maximum standard uptake value
      (SUV) of the most conspicuous bone lesion at baseline FDG PET. PET results were
      compared to the overall assessment of response (response, stable disease,
      progressive disease) with a combination of conventional imaging, change in tumor
      marker values, and subjective symptom changes by experienced medical oncologists
      blinded to the findings at FDG PET. Changes in FDG SUV were also correlated
      quantitatively to the changes in a particular tumor marker (CA 27.29). RESULTS:
      The changes in FDG SUV with therapy showed correlation with the overall clinical
      assessment of response (P < .01). The percentage change in FDG uptake with
      therapy showed strong correlation with the percentage change in tumor marker
      value (P < .01). CONCLUSION: Preliminary results indicate that serial whole-body
      FDG PET can help quantitatively assess the response of breast cancer bone
      metastases to therapy. Prospective trials are needed to further investigate its
      accuracy.

PMID- 12186441
TI  - Development of perfusion CT software for personal computers.
AB  - RATIONALE AND OBJECTIVES: The authors developed software for creating
      quantitative maps of arterial and portal perfusion in the upper abdominal organs
      on personal computers. The image quality of these perfusion computed tomographic
      (CT) images was visually evaluated. MATERIALS AND METHODS: In 58 patients (38
      men, 20 women; mean age, 63.9 years +/- 11.9; range, 22-85 years) with various
      diseases of the upper abdomen, 91 single-section dynamic CT studies were
      obtained. The data were transferred on-line to a personal computer, and
      quantitative maps of arterial and portal perfusion were created by means of the
      maximum-slope method. Perfusion CT images were reviewed by a radiologist and a
      radiation technologist, and image quality was rated according to a four-category
      scoring system (1 = good quality, 2 = moderate, 3 = poor, 4 = images could not be
      created). RESULTS: Arterial perfusion CT images could be created in 81 (89%) of
      91 examinations, and 74 images (81%) were scored as 1 or 2. Portal perfusion CT
      images could be created in 60 (68%) of 88 examinations, in which a portal trunk
      was included in the section, and 33 of them (38%) were scored as 1 or 2. Patient
      motion during dynamic CT sequences resulted in poor image quality in seven
      arterial and 27 portal perfusion images. CONCLUSION: Perfusion CT can combine
      quantitative perfusion maps with good anatomic detail in one image, although
      patient movement frequently degrades image quality in portal perfusion CT.

PMID- 12186442
TI  - Development of novel tumor imaging agents with phage-display combinatorial
      peptide libraries.
AB  - RATIONALE AND OBJECTIVES: Current radiologic methods do not provide sufficient
      information for unambiguous diagnosis and prognosis of cancer. The present
      investigation sought to address this deficiency by developing a system for
      designing novel small molecules targeted against tumor-specific molecules for use
      as radionuclide imaging agents. MATERIALS AND METHODS: Part of a tumor-specific
      receptor, purified recombinant epidermal growth factor receptor (EGFR), variant
      III, extracellular domain (rEGFRvIII-ecd), was used as the target in the
      selection of EGFRvIII-specific peptide ligands from random peptide bacteriophage
      (phage) display libraries. After three rounds of screening, phage isolates were
      tested for binding affinity with an enzyme-linked immunosorbent assay. Positive
      phage were sequenced, and the peptides were synthesized and tested for binding
      affinity with a surface plasmon resonance assay. RESULTS: Affinity screening
      identified 49 peptide-expressing phage that showed enhanced binding to the
      variant receptor compared with wild-type EGFR. Free peptides from the two phage
      isolates exhibiting the most favorable binding were tested for target binding.
      One of these demonstrated a binding affinity for rEGFRvIII-ecd in the 30-nmol/L
      range. CONCLUSION: These data suggest that phage display libraries may be very
      useful in the design of novel, high-affinity tumor imaging agents.

PMID- 12186443
TI  - Feasibility of MR imaging-guided breast lumpectomy for malignant tumors in a 0.5
      T open-configuration MR imaging system.
AB  - RATIONALE AND OBJECTIVES: The authors performed this study to develop the
      technology for and evaluate the utility of a 0.5-T vertical open-configuration
      magnetic resonance (MR) imaging system for imaging-guided breast lumpectomy of
      malignant tumors. MATERIALS AND METHODS: Twenty women with breast cancer
      underwent MR imaging-guided lumpectomy in a 0.5-T vertical open-configuration MR
      system. During lumpectomy, pre- and postresection images were acquired with and
      without contrast material. Images were used both for tumor localization and to
      monitor resection. If residual enhancement was observed, additional resection was
      performed in an effort to secure negative pathologic margins. RESULTS: The
      procedure evolved over time with technology innovations and improvements.
      Specifically, instruments were acquired that were compatible with MR imaging
      breast procedures, the echo time with the Dixon technique was modified to
      optimize image quality, contrast material injection was timed for maximum lesion
      enhancement, breath-hold image acquisition was instituted, and the biopsy cavity
      was filled with saline and the incision closed before image acquisition.
      CONCLUSION: All breast lesions were identified despite limited spatial resolution
      and fat-suppression techniques. The evolved techniques facilitated intraoperative
      margin evaluation and prompted additional surgical margin resection in five
      patients, sparing four from an additional surgical procedure. Intraoperative MR
      imaging has the potential to improve the complete pathologic excision of invasive
      breast cancer.

PMID- 12186444
TI  - Clinical imaging with optical coherence tomography.

PMID- 12186445
TI  - Impact of pager notification on report verification times.
AB  - RATIONALE AND OBJECTIVES: The purpose of this study was to assess the impact on
      times of verification (TOVs) by a pager notification system (PNS) that informs
      physicians when reports are available for signature. MATERIALS AND METHODS: An
      automated PNS was implemented in the authors' department in November 2000.
      Monthly report verification times of each physician were collected for 3 months
      in the years before and after initiation of the PNS. Radiologists enrolled in the
      PNS and those who were not were assigned into two groups for analysis. Mean TOVs
      for the two sets of 3 months and for the two groups were calculated and
      differences recorded. Two-tailed t tests were used to assess for statistical
      differences between the groups. RESULTS: Twenty-nine of 37 radiologists
      voluntarily enrolled in the PNS (group 1). Mean TOV was 26.75 hours (standard
      deviation [SD] = 17.76) for these physicians before and 14.48 hours (SD = 11.86)
      after the PNS was employed (P < .01). For those physicians who did not enroll in
      the PNS, mean TOV was 11.53 hours (SD = 5.55) before and 9.77 hours (SD = 9.86)
      after the PNS was employed (P = .33). Both the absolute and percentage reductions
      in TOVs were significantly greater for those physicians enrolled in the PNS than
      for those who were not (P = .035). Twenty-three of 29 (79%) physicians who used
      the PNS showed a reduction in their report turnaround times. CONCLUSION: Linking
      the PNS with the radiology information system to notify physicians of unsigned
      reports was effective in reducing report verification times.

PMID- 12186446
TI  - Getting the most out of a radiology department education committee.
AB  - Regular meetings of residency program teaching faculty are required by the ACGME
      and support the educational mission of the department. The education committee
      should be viewed by the department chair and other members of the faculty as
      being equally important as the departmental research, operations, and finance
      committees. An education committee that is dedicated to promoting excellence in
      education and supports the educational mission of the department will enhance the
      department's local, regional, and national reputation.

PMID- 12186447
TI  - Should pay in radiology be tied to productivity? The case against.

PMID- 12186448
TI  - The typewriter.

PMID- 12186449
TI  - Opportunities for research with the American College of Radiology Imaging Network
      (ACRIN) image database.

PMID- 12186450
TI  - Ultra-early surgery for aneurysmal subarachnoid hemorrhage: outcomes for a
      consecutive series of 391 patients not selected by grade or age.
AB  - OBJECT: This study was undertaken to determine the outcomes in an unselected
      group of patients treated with semiurgent surgical clipping of aneurysms
      following subarachnoid hemorrhage (SAH). METHODS: A clinical management outcome
      audit was conducted to determine outcomes in a group of 391 consecutive patients
      who were treated with a consistent policy of ultra-early surgery (all patients
      treated within 24 hours after SAH and 85% of them within 12 hours). All
      neurological grades were included, with 45% of patients having poor grades (World
      Federation of Neurosurgical Societies [WFNS] Grades IV and V). Patients were not
      selected on the basis of age; their ages ranged between 15 and 93 years and 19%
      were older than 70 years. The series included aneurysms located in both anterior
      and posterior circulations. Eighty-eight percent of all patients underwent
      surgery and only 2.5% of the series were selectively withdrawn (by family
      request) from the prescribed surgical treatment. In patients with good grades
      (WFNS Grades I-III) the 3-month postoperative outcomes were independence (good
      outcome) in 84% of cases, dependence (poor outcome) in 8% of cases, and death in
      9%. In patients with poor grades the outcomes were independence in 40% of cases,
      dependence in 15% of cases, and death in 45%. There was a 12% rate of rebleeding
      with all cases of rebleeding occurring within the first 12 hours after SAH;
      however, outcomes of independence were achieved in 46% of cases in which
      rebleeding occurred (43% mortality rate). Rebleeding was more common in patients
      with poor grades (20% experienced rebleeding, whereas only 5% of patients with
      good grades experienced rebleeding). CONCLUSIONS: The major risk of rebleeding
      after SAH is present within the first 6 to 12 hours. This risk of ultra-early
      rebleeding is highest for patients with poor grades. Securing ruptured aneurysms
      by surgery or coil placement on an emergency basis for all patients with SAH has
      a strong rational argument.

PMID- 12186451
TI  - Dissecting aneurysms of the vertebral artery: a management strategy.
AB  - OBJECT: The authors present a retrospective analysis of their experience in the
      treatment of vertebral artery (VA) dissecting aneurysms and propose a management
      strategy for such aneurysms, with special emphasis on the most formidable VA
      dissecting aneurysms, which involve the origin of the posterior inferior
      cerebellar artery (PICA). METHODS: Since 1998, 18 patients with VA dissecting
      aneurysms, 11 of whom presented with subarachnoid hemorrhage (SAH), have been
      treated by endovascular surgery at the authors' institution. Obliteration of the
      entire segment of the dissected site with coils (internal trapping) was performed
      for aneurysms without involvement of the origin of the PICA (12 cases; among
      these the treatment-related morbidity rate was 16.7%). The treatment strategy
      applied to PICA-involved VA dissecting aneurysms presenting with SAH (three
      cases) included proximal occlusion of the parent artery followed by internal
      trapping of the aneurysm (one case), proximal occlusion of the parent artery
      followed by occipital artery (OA)-PICA bypass (one case), and two-staged internal
      trapping of the aneurysm involving double PICAs (one case). For PICA-involved VA
      dissecting aneurysms that were not associated with SAH at presentation (three
      cases), OA-PICA bypass was performed and followed by internal trapping of the
      aneurysm (two cases). In the remaining case in which a fetal-type posterior
      communicating artery was present, internal trapping was performed following
      successful balloon test occlusion (BTO). Overall, there was no sign of infarction
      in the PICA territory, despite complete occlusion of aneurysms involving the
      PICA. There was no recurrent bleeding or ischemic symptoms during the follow-up
      periods. The overall treatment-related morbidity rate for the VA dissecting
      aneurysms involving the PICA was 16.7%. CONCLUSIONS: Dissecting VA aneurysms that
      do not involve the PICA can be safely treated by internal trapping. For those
      lesions that do involve the PICA, a decision-making algorithm is advocated to
      maximize the efficacy of the treatment as well as to minimize the risks of
      treatment-related morbidity based on BTO.

PMID- 12186452
TI  - Evaluation of changes in circulating blood volume during acute and very acute
      stages of subarachnoid hemorrhage: implications for the management of
      hypovolemia.
AB  - OBJECT: Circulating blood volume (cBV) is reported to decrease in patients who
      suffer a subarachnoid hemorrhage (SAH), but little is known about the correlation
      between changes in cBV, and patient clinical condition and time course after SAH,
      especially during the very acute stage. To determine appropriate management of
      patients with SAH, the authors measured cBV by using pulse spectrophotometry
      immediately after patient admission. They also evaluated whether the timing of
      surgery influenced changes in cBV. METHODS: Circulating blood volume was measured
      in a total of 73 patients who were divided into the following three groups: Group
      A (very acute SAH) consisted of 14 SAH cases, Group B (acute SAH) included 34 SAH
      cases, and Group C (controls) included 25 other neurosurgical cases. All patients
      in Group A underwent aneurysm clipping within 6 hours after onset of SAH, whereas
      all patients in Group B underwent aneurysm clipping within 72 hours after onset.
      Hypervolemic therapy was not performed in patients with SAH. Before surgery, cBV
      was significantly lower in patients in Group B than in those in Group C, but
      there was no significant difference in this parameter when comparing Groups A and
      C. Although there was a transient drop in cBV in Group B patients for at least 3
      days after surgery, there was no significant change in cBV in Group A patients
      during the study period. None of the Group A patients suffered from symptomatic
      vasospasm; however, four Group B patients did experience symptomatic vasospasm.
      CONCLUSIONS: The authors assert that normovolemic fluid management is appropriate
      for patients who undergo surgery during the very acute stage of SAH, whereas a
      relatively hypervolemic therapy is necessary for 3 to 5 days after operation to
      prevent early hypovolemia in patients who undergo surgery during the acute stage
      of SAH.

PMID- 12186453
TI  - Free fatty acids in human cerebrospinal fluid following subarachnoid hemorrhage
      and their potential role in vasospasm: a preliminary observation.
AB  - OBJECT: The mechanisms leading to vasospasm following subarachnoid hemorrhage
      (SAH) remain unclear. Accumulation in cerebrospinal fluid (CSF) of free fatty
      acids (FFAs) may play a role in the development of vasospasm; however, in no
      previous study have concentrations of FFAs in CSF been examined after SAH.
      METHODS: We collected samples of CSF from 20 patients with SAH (18 cases of
      aneurysmal SAH and two cases of spontaneous cryptogenic SAH) and used a high
      performance liquid chromatography assay to determine the FFA concentrations in
      these samples. We then compared these findings with FFA concentrations in the CSF
      of control patients. All FFA concentrations measured 24 hours after SAH were
      significantly greater than control concentrations (p < 0.01 for palmitic acid and
      < 0.001 for all other FFAs). All measured FFAs remained elevated for the first 48
      hours after SAH (p < 0.05 for linoleic acid, p < 0.01 for palmitic acid, and p <
      0.001 for the other FFAs). After 7 days, a second elevation in all FFAs was
      observed (p < 0.05 for linoleic acid, p < 0.01 for palmitic acid, and p < 0.001
      for the other FFAs). Samples of CSF collected within 48 hours after SAH from
      patients in whom angiography and clinical examination confirmed the development
      of vasospasm after SAH were found to have significantly higher concentrations of
      arachidonic, linoleic, and palmitic acids than samples collected from patients in
      whom vasospasm did not develop (p < 0.05). CONCLUSIONS: Following SAH, all FFAs
      are initially elevated. A secondary elevation occurs between 8 and 10 days after
      SAH. This study provides preliminary evidence of FFA elevation following SAH and
      of a potential role for FFAs in SAH-induced vasospasm. A prospective study is
      warranted to determine if CSF concentrations of FFAs are predictive of vasospasm.

PMID- 12186454
TI  - Transcranial approach for venous embolization of dural arteriovenous fistulas.
AB  - OBJECT: Transvenous embolization is effective in the treatment of an intracranial
      dural arteriovenous fistula (DAVF). Access to the fistula via the internal
      jugular vein (IJV) may be limited by associated dural sinus thrombosis; a
      transcranial approach has been developed for venous embolization in such a
      situation. The authors report their experiences with the use of a transcranial
      approach for venous embolization of DAVFs. METHODS: Ten patients with DAVFs
      underwent craniectomy and embolization procedures in which direct sinus puncture
      was performed. The DAVFs were located inside the dura mater that constituted the
      walls of the transverse sinus in five cases, the superior sagittal sinus in four
      cases, and the superior petrosal sinus in one case. All DAVFs drained directly
      into a sinus with secondary reflux into leptomeningeal veins. In all cases, the
      fistula could not be accessed from the IJVs. Craniectomy was performed in an
      operating room and, in seven cases, subsequent enlargement of the craniectomy was
      required. Sinus catheterization was performed after the patient had been
      transferred to the angiography room. The DAVFs were embolized using coils only in
      five patients, glue only in two patients, and both coils and glue in three
      patients. Angiographic confirmation that embolization of the fistula was
      successful was obtained in all cases. A transient complication occurred during
      the first case after sinus catheterization was attempted in the operating room.
      CONCLUSIONS: The transcranial approach allows straightforward access to DAVFs
      located on superficial dural sinuses that are inaccessible from the IJVs. The
      effectiveness of this approach is similar to that of the standard retrograde
      venous approach. The correct location and adequate extent of the craniectomy are
      essential for success to be achieved using this technique.

PMID- 12186455
TI  - Changing patterns of insulin-like growth factor-I and glucose-suppressed growth
      hormone levels after pituitary surgery in patients with acromegaly.
AB  - OBJECT: According to a recent consensus statement on the treatment of acromegaly,
      its biochemical cure is defined as the normalization of age- and sex-adjusted
      insulin-like growth factor (IGF)-I levels and the suppression of growth hormone
      (GH) by glucose to lower than 1 ng/ml. The present study was prompted by the
      clinical observation that many cases of acromegaly can be considered cured
      according to one criterion but not others at different moments in a patient's
      postoperative course. METHODS: Fifty-three patients with acromegaly (30 women and
      23 men) harboring nine microadenomas and 44 macroadenomas were evaluated after
      surgery by assessing age- and sex-adjusted IGF-I levels as well as glucose
      suppressed GH levels. Fifty of these patients were studied more than once during
      follow up. Acromegaly was categorized as cured if the patient's IGF-I level was
      normal and their glucose-suppressed GH level was lower than 1 ng/ml; the disease
      was considered to be active if the patient's IGF-I level was high and the GH
      nadir was higher than 1 ng/ml following administration of glucose. Discordant
      categories of the disease were found in patients with high IGF-I levels and a GH
      nadir lower than 1 ng/ml after glucose administration and in those with normal
      IGF-I levels and a GH nadir higher than 1 ng/ml after glucose intake. At the
      first postoperative biochemical evaluation (1-3 months), 34% of patients
      harboring macroadenomas were classified as having been cured of acromegaly, 39%
      as having the active disease, and 27% as having the discordant form of the
      disease. When last evaluated (> or = 12 months postoperatively), the percentage
      of patients with the discordant form dropped to 14% and the proportion of cases
      cured and active was 44% and 41%, respectively. Of the nine patients with
      microadenomas, 44.4% were cured of acromegaly, 33.2% had the active disease, and
      22% had the discordant variety on first evaluation. Twelve months or longer after
      transsphenoidal surgery, 55.5% of cases were cured, 11.1% were active, and 33%
      were discordant. In most cases, the discordant variety developed because of a
      persistently elevated level of IGF-I, followed by an incompletely suppressed GH
      level. Nineteen patients (38%) modified their biochemical category. In 15 of
      these patients this change in category was due to a change in IGF-I levels,
      becoming normal in 12 patients and rising to above normal range in three. A tumor
      remnant was demonstrated on magnetic resonance images in only four of these 19
      patients. CONCLUSIONS: The authors conclude that the discordance rate between the
      biochemical markers that define cure in acromegaly is higher than previously
      reported, and the biochemical status assigned to a patient early in the
      postoperative course is very likely to change later, particularly when initially
      discordant.

PMID- 12186456
TI  - Surgical complications associated with the endoscopic endonasal transsphenoidal
      approach for pituitary adenomas.
AB  - OBJECT: To assess postoperative complications related to the surgical procedure,
      a retrospective analysis was conducted in a series of 146 consecutively treated
      patients who underwent an endoscopic endonasal transsphenoidal approach to the
      sellar region for resection of pituitary adenomas between January 1997 and July
      2001. METHODS: Complications were divided into groups (nasofacial, sphenoid
      sinus, sella turcica, supra or parasellar, and endocrine complications) according
      to the anatomical structures and the systems involved. Overall, a decreased
      incidence of complications has been observed, compared with large historical
      series of the traditional microsurgical transsphenoidal approach, likely because
      of the overview inside the anatomy facilitated by the endoscope, and the
      decreased surgical trauma. CONCLUSIONS: Transsphenoidal surgery, either
      microscopic or endoscopic, is a safe procedure in experienced hands, but serious
      complications still occur and must be reduced as much as possible. Additional
      improvement can be expected with greater experience and new technical
      developments. A coordinated team effort with other dedicated colleagues from
      different specialties is advised.

PMID- 12186457
TI  - Giant prolactinomas: clinical management and long-term follow up.
AB  - OBJECT: Giant prolactinomas are rare tumors whose treatment and outcome has only
      been addressed in isolated case reports. The authors document the long-term
      follow-up findings and clinical outcome in a group of patients with giant
      prolactinomas. METHODS: This study is a retrospective chart and clinical review
      of more than 2000 cases of pituitary tumors treated at the authors' institution,
      of which 10 met the criteria for inclusion (prolactin level > 1000 ng/ml,
      diameter > 4 cm on neuroimaging studies, and clinical signs of
      hyperprolactinemia/mass effect). The average follow-up duration was 6.7 years
      after initial treatment with either bromocriptine or transsphenoidal resection.
      In more than 90% of the patients in this series the disease was controlled by
      medical treatment with bromocriptine alone; the other 10% required early surgery
      via transsphenoidal resection. All patients had improvement in visual symptoms.
      All tumors had extrasellar components, five of which exhibited frank invasion of
      the cavernous sinus. Tumor volume on magnetic resonance imaging was decreased on
      average by 69%; this occurred at a faster rate and in larger amounts when treated
      with bromocriptine than has been reported in the literature for
      macroprolactinomas. CONCLUSIONS: According to long-term follow-up findings, giant
      prolactinomas are exquisitely responsive to dopamine agonist therapy. In giant
      prolactinomas the prolactin level does not correlate with size. The main
      indication for early surgery is intratumoral hematoma, whereas our main
      indications for late surgery are cerebrospinal fluid leakage caused by medical
      treatment, or an increasing prolactin level despite medical therapy. Checking
      prolactin levels in suspicious sellar and/or suprasellar lesions may be
      diagnostic and prevent unnecessary surgery.

PMID- 12186458
TI  - Predictive value of serum prolactin levels measured immediately after
      transsphenoidal surgery.
AB  - OBJECT: Prolactin-secreting pituitary adenomas may be managed by surgery,
      medication, radiotherapy, or observation. The authors reviewed a consecutive
      series of patients who were followed for at least 5 years after surgery to assess
      the prognostic significance of preoperative factors (tumor size and prolactin
      level) and an immediate postoperative factor (prolactin level obtained the
      morning after surgery) on long-term hormonal outcome, thereby clarifying the
      indications for surgical removal of tumor, the definition of successful treatment
      outcomes, and the nature of "recurrent" tumors. METHODS: Between 1979 and 1991,
      241 patients with prolactinomas underwent transsphenoidal resection. Nineteen
      patients were lost to follow-up review, whereas the remaining 222 patients
      underwent measurement of their prolactin levels on postoperative Day 1 (POD 1),
      at 6 and 12 weeks, and every 6 months thereafter for a minimum of 5 years. On POD
      1, prolactin levels in 133 patients (Group 1) were lower than 10 ng/ml, in 43
      patients (Group 2) between 10 and 20 ng/ml, and in 46 patients (Group 3) higher
      than 20 ng/ml. At 6 and 12 weeks, normal prolactin levels (< or = 20 ng/ml) were
      measured in 132 (99%) of the 133 patients in Group 1 but only in 32 (74%) of the
      43 patients in Group 2. By 5 years postoperatively, normal levels of prolactin
      were still measured in 130 patients (98%) in Group 1 compared with only five
      patients (12%) in Group 2. No patient with a prolactin level lower than 3 ng/ml
      on POD 1 was found to have an elevated hormone level at 5 years. The likelihood
      of a long-term chemical cure was greater for patients with microadenomas (91%
      cure rate) than for those with macroadenomas (33%). Preoperative prolactin levels
      also correlated with hormonal outcome. CONCLUSIONS: Prolactin levels lower than
      10 ng/ml on POD 1 predict a long-term chemical cure in patients with
      microadenomas (100% cure rate) and those with macroadenomas (93% cure rate). In
      contrast, a cure is not likely to be obtained in patients with normal levels
      ranging between 10 and 20 ng/ml on POD 1 if they harbor macroadenomas (0% cure
      rate). A recurrence reported several years after surgery probably represents the
      presence of persistent tumor that was not originally removed. If the initial
      operation was performed by an experienced surgeon, however, reoperation is not
      likely to yield a chemical cure.

PMID- 12186459
TI  - Long-term functional outcome after selective posterior rhizotomy.
AB  - OBJECT: Selective posterior rhizotomy (SPR) is a well-recognized treatment for
      children with spastic cerebral palsy (CP). Few investigators have used
      quantitative outcome measures to assess the surgical results beyond 3 years. The
      authors analyzed data obtained from the McGill Rhizotomy Database to determine
      the long-term functional outcome of children who had undergone selective dorsal
      rhizotomy accompanied by intraoperative electrophysiological monitoring. METHODS:
      The study population was composed of children with spastic CP who underwent SPR
      and were evaluated by a multidisciplinary team preoperatively, and at 6 months
      and 1 year postoperatively. Quantitative standardized assessments of lower-limb
      spasticity, passive range of motion, muscle strength, and ambulatory function
      were obtained. Of the 93 patients who met the entry criteria for the study, 71
      completed the 3-year and 50 completed the 5-year assessments, respectively.
      Statistical analysis demonstrated significant improvements in spasticity, range
      of motion, and functional muscle strength at 1 year after SPR. The preoperative,
      1-, 3-, and 5-year values for the global score of the Gross Motor Function
      Measure were 64.6, 70.8, 80, and 85.6, respectively. The greatest improvement
      occurred in the dimensions reflecting lower-extremity motor function, where the
      mean change was 10.1% at 1 year, 19.9% at 3 years, and 34.4% at the 5-year follow
      up review in comparison with the baseline value. This was associated with a
      lasting improvement in alignment and postural stability during developmental
      positions, as well as increased ability to perform difficult transitional
      movements. CONCLUSIONS: The results of this study support the presence of
      significant improvements in lower-limb functional motor outcome 1 year after SPR,
      and the improvements persist at 3 and 5 years. The authors conclude that SPR in
      conjunction with intraoperative stimulation is valuable for permanently
      alleviating lower-limb spasticity while augmenting motor function.

PMID- 12186460
TI  - Predicting recovery in patients suffering from traumatic brain injury by using
      admission variables and physiological data: a comparison between decision tree
      analysis and logistic regression.
AB  - OBJECT: Decision tree analysis highlights patient subgroups and critical values
      in variables assessed. Importantly, the results are visually informative and
      often present clear clinical interpretation about risk factors faced by patients
      in these subgroups. The aim of this prospective study was to compare results of
      logistic regression with those of decision tree analysis of an observational,
      head-injury data set, including a wide range of secondary insults and 12-month
      outcomes. METHODS: One hundred twenty-four adult head-injured patients were
      studied during their stay in an intensive care unit by using a computerized data
      collection system. Verified values falling outside threshold limits were analyzed
      according to insult grade and duration with the aid of logistic regression. A
      decision tree was automatically produced from root node to target classes
      (Glasgow Outcome Scale [GOS] score). Among 69 patients, in whom eight insult
      categories could be assessed, outcome at 12 months was analyzed using logistic
      regression to determine the relative influence of patient age, admission Glasgow
      Coma Scale score, Injury Severity Score (ISS), pupillary response on admission,
      and insult duration. The most significant predictors of mortality in this patient
      set were duration of hypotensive, pyrexic, and hypoxemic insults. When good and
      poor outcomes were compared, hypotensive insults and pupillary response on
      admission were significant. Using decision tree analysis, the authors found that
      hypotension and low cerebral perfusion pressure (CPP) are the best predictors of
      death, with a 9.2% improvement in predictive accuracy (PA) over that obtained by
      simply predicting the largest outcome category as the outcome for each patient.
      Hypotension was a significant predictor of poor outcome (GOS Score 1-3). Low CPP,
      patient age, hypocarbia, and pupillary response were also good predictors of
      outcome (good/poor), with a 5.1% improvement in PA. In certain subgroups of
      patients pyrexia was a predictor of good outcome. CONCLUSIONS: Decision tree
      analysis confirmed some of the results of logistic regression and challenged
      others. This investigation shows that there is knowledge to be gained from
      analyzing observational data with the aid of decision tree analysis.

PMID- 12186461
TI  - Hearing preservation in acoustic neuroma surgery: importance of adhesion between
      the cochlear nerve and the tumor.
AB  - OBJECT: To evaluate the possible prognostic factors for hearing preservation, the
      authors retrospectively reviewed the results of 30 consecutive acoustic neuroma
      operations in which hearing preservation was attempted, in a total series of 63
      acoustic neuromas. METHODS: Intracanalicular tumors or those that extended less
      than 3 mm outside the porus acusticus (10 cases) were resected via the middle
      fossa approach. The retrosigmoid approach was used for tumors exceeding the
      limits for the middle fossa approach (20 cases). Overall, hearing was preserved
      (pure tone average < or = 50 dB and speech discrimination score > or = 50%) in 21
      patients (70%). There were 11 patients with severe adhesion between the cochlear
      nerve and tumor capsule, and 19 without. Hearing was preserved postoperatively in
      only two (18.2%) of 11 patients with severe adhesion, whereas all 19 without
      severe adhesion had hearing preservation. CONCLUSIONS: The presence or absence of
      severe adhesion in the interface between the cochlear nerve and the tumor might
      be the most significant prognostic factor for hearing preservation postsurgery.

PMID- 12186462
TI  - Stabilization of disease progression by hydroxyurea in patients with recurrent or
      unresectable meningioma.
AB  - OBJECT: The management of certain meningiomas of the skull base and those
      involving the dural venous sinuses remains a challenge. In recent reports it has
      been suggested that hydroxyurea chemotherapy can cause regression of unresectable
      and recurrent meningiomas. The authors report their experience in using
      hydroxyurea for the treatment of patients with recurrent or unresectable
      meningiomas. METHODS: Hydroxyurea was administered at a dosage of approximately
      20 mg/kg/day to 11 women and nine men (median age 59 years, range 31-75 years)
      with recurrent or unresectable intracranial meningiomas (12 basal, two
      parasagittal, and six multiple). In 16 patients the meningiomas were benign, in
      three they had atypical features, and in one the meningioma was malignant. All
      patients had measurable residual disease. Four patients with benign meningiomas
      had previously received radiotherapy (two were treated with conventional
      fractionated radiotherapy and two with stereotactic radiosurgery), three with
      atypical meningiomas received conventional fractionated radiotherapy, and the one
      with a malignant meningioma received conventional radiotherapy with additional
      stereotactic radiosurgery. Tumor enlargement was documented in all patients on
      neuroimages obtained before initiation of hydroxyurea therapy. All patients were
      evaluable for response to therapy. In 12 patients with benign meningiomas, the
      disease had stabilized on neuroimages obtained posttreatment (median duration of
      treatment 122 weeks, range 8-151 weeks), and two of these showed clinical
      improvement. One patient with a benign meningioma experienced a minor partial
      response that was noted after 39 weeks of treatment and was confirmed on
      neuroimaging and clinical evaluations. In three others with benign meningiomas,
      progression was confirmed on neuroimages obtained after 41, 55, and 66 weeks,
      respectively: the 1-year freedom from progression rate was 0.93 (standard error
      0.07) in patients with benign meningiomas. In three patients with atypical
      meningiomas, the tumors had progressed on neuroimages obtained after 12, 19, and
      45 weeks, respectively. In the patient with a malignant meningioma, progression
      was confirmed on neuroimages obtained at 24 weeks. Hydroxyurea has been
      reasonably well tolerated, although one patient discontinued therapy because of
      moderate myelosuppression. CONCLUSIONS: Although tumor regression appears
      uncommon, these results indicate that hydroxyurea may arrest progression of
      unresectable or recurrent benign meningiomas.

PMID- 12186463
TI  - Stereotactic radiosurgery for idiopathic trigeminal neuralgia.
AB  - OBJECT: Each year a greater number of patients with trigeminal neuralgia (TN)
      undergo radiosurgery, including a large number of patients who are candidates for
      microvascular decompression (MVD). METHODS: The case characteristics and outcomes
      of 117 consecutive patients who underwent radiosurgery were retrieved from a
      prospectively maintained database. The mean patient age was 67.8 years; and the
      majority (58%) of patients had undergone surgery previously. The dependent
      variable for all analyses of facial pain was complete pain relief without
      medication (excellent outcome). Median follow-up duration was 26 months (range 1
      48 months). The actuarial rate of achieving and maintaining an excellent outcome
      was 57% and 55% at 1 and 3 years, respectively, after radiosurgery. A greater
      percentage of patients who had not previously undergone surgery achieved and
      maintained excellent outcomes (67% at 1 and 3 years) than that of patients who
      had undergone prior surgery (51% and 47% at 1 and 3 years, respectively; relative
      risk [RR] = 1.77, 95% confidence interval [CI] 1.01-3.13, p = 0.04). New
      persistent trigeminal dysfunction was noted in 43 patients (37%). Tolerable
      numbness or paresthesias occurred in 29 patients (25%), whereas bothersome
      dysesthesias developed in 14 patients (12%). Only a radiation dose of 90 Gy
      correlated with new trigeminal deficits or dysesthesias (RR = 3.10, 95% CI 1.64
      5.81, p < 0.001). Excellent outcomes in patients with new trigeminal dysfunction
      were achieved and maintained at rates of 76% and 74% at 1 and 3 years,
      respectively, after radiosurgery, compared with respective rates of 46% and 42%
      in patients who did not experience postradiosurgery trigeminal dysfunction (RR =
      4.53, 95% CI 2.03-9.95, p < 0.01). CONCLUSIONS: Radiosurgical treatment provides
      complete pain relief for the majority of patients with idiopathic TN. There is a
      strong correlation between the development of new facial sensory loss and
      achievement and maintenance of pain relief after this procedure. Because the long
      term results of radiosurgery still remain unknown, MVD should continue to be the
      primary operation for medically fit patients with TN.

PMID- 12186464
TI  - Histological yield, complications, and technological considerations in 114
      consecutive frameless stereotactic biopsy procedures aided by open intraoperative
      magnetic resonance imaging.
AB  - OBJECT: The authors undertook a prospective study of frameless, magnetic
      resonance (MR)-guided stereotactic brain biopsy procedures performed with the aid
      of an open MR system. Morbidity and mortality rates, frequency of postoperative
      hemorrhage, and histological yield were evaluated, as well as the size and
      location of the lesions under investigation. METHODS: During a period of 51
      months (July 1996-November 2000), 114 consecutive frameless stereotactic biopsy
      procedures were performed with the aid of an open intraoperative MR system to
      investigate supratentorial lesions in 113 patients. The median volume of the
      lesions was 33.5 cm3, and 31.9% were deep seated. All biopsy samples comprised
      pathological tissue and in 111 (97.4%) of 114 a specific neuropathological
      diagnosis was made. A follow-up computerized tomography (CT) scan was obtained on
      the 1st postoperative day in all patients to evaluate postoperative
      complications. In two cases (1.8%), a hemorrhage was found on postoperative CT
      scans, with no neurological worsening of the patients. Morbidity with
      neurological worsening was seen in three patients; it was transient in two of
      them (1.8%), and in one (0.9%) subsequent emergency craniotomy was necessary
      because of increased edema. There were no infections, but there was one death
      (0.9%) CONCLUSIONS: Open intraoperative MR imaging transforms a blind
      conventional stereotactic procedure into a visually controlled procedure that is
      adaptable to dynamic anatomical changes. Routine postprocedural MR imaging makes
      follow-up CT scanning obsolete. This largest reported series of intraoperative MR
      guided biopsy procedures shows results that are at least comparable with those in
      reports of larger series of conventional stereotactic biopsy sampling. The mean
      procedure time was 60 minutes including planning, and this method produced low
      morbidity and complication rates and a high histological yield.

PMID- 12186465
TI  - Absence of movement disorders after surgical resection of glioma invading the
      right striatum.
AB  - OBJECT: Despite the high frequency of striatal lesions, the rate of movement
      disorders reported in the literature is lower than expected (< 10%). To maximize
      the extent of resection in low-grade gliomas invading the right striatum, the
      authors performed a striatal resection in a series of 14 patients, observed the
      lack of movement disorders following these procedures, and discuss herein the
      mechanisms likely to explain these findings. METHODS: Fourteen patients harboring
      a low-grade glioma that was infiltrating the right nondominant striatum, and in
      whom the results of neurological examination were normal, underwent surgery in
      which intraoperative electrical mapping was used, allowing the identification of
      pyramidal pathways. The striatum was resected in all procedures, and
      corticospinal tracts were systematically detected and preserved. Ten patients
      presented with a transient postoperative motor deficit, and nine with a loss of
      interest and affect. These symptoms all resolved within 3 months, except for one
      case of persistent hemiparesis. No postoperative movement disorder was noted,
      even transitorily. All resections were categorized as either total or subtotal on
      control magnetic resonance images. CONCLUSIONS: These findings show that the
      nondominant striatum can be removed in cases of glioma invasion without inducing
      even transitory movement disorders. This phenomenon could be explained by the
      combined resection of the two classes of striatal neurons, an associated pallidal
      and thalamocortical resection, or a compensatory recruitment of parallel
      networks. Thus, these results may allow the surgeon to maximize the extent of
      removal of low-grade gliomas involving basal ganglia. Striatal resection may
      induce transient hemiparesis and "athymhormic syndrome," however, necessitating
      that the patient be clearly informed before surgery.

PMID- 12186466
TI  - Implantation of deep brain stimulators into the subthalamic nucleus: technical
      approach and magnetic resonance imaging-verified lead locations.
AB  - OBJECT: Chronic deep brain stimulation (DBS) of the subthalamic nucleus (STN) is
      a procedure that is rapidly gaining acceptance for the treatment of symptoms in
      patients with Parkinson disease (PD), but there are few detailed descriptions of
      the surgical procedure itself. The authors present the technical approach used to
      implant 76 stimulators into the STNs of patients with PD and the lead locations,
      which were verified on postoperative magnetic resonance (MR) images. METHODS:
      Implantation procedures were performed with the aid of stereotactic MR imaging,
      microelectrode recording (MER) in the region of the stereotactic target to define
      the motor area of the STN, and intraoperative test stimulation to assess the
      thresholds for stimulation-induced adverse effects. All patients underwent
      postoperative MR imaging, which was performed using volumetric gradient-echo and
      T2-weighted fast-spin echo techniques, computational reformatting of the MR image
      into standard anatomical planes, and quantitative measurements of lead location
      with respect to the midcommissural point and the red nucleus. Lead locations were
      statistically correlated with physiological data obtained during MER and
      intraoperative test stimulation. CONCLUSIONS: The authors' approach to
      implantation of DBS leads into the STN was associated with consistent lead
      placement in the dorsolateral STN, a low rate of morbidity, efficient use of
      operating room time, and robust improvement in motor function. The mean
      coordinates of the middle of the electrode array, measured on postoperative MR
      images, were 11.6 mm lateral, 2.9 mm posterior, and 4.7 mm inferior to the
      midcommissural point, and 6.5 mm lateral and 3.5 mm anterior to the center of the
      red nucleus. Voltage thresholds for several types of stimulation-induced adverse
      effects were predictive of lead location. Technical nuances of the surgery are
      described in detail.

PMID- 12186467
TI  - Functional topography of the low postcentral area.
AB  - OBJECT: The goal of this study was to establish a reliable method for
      identification of face and tongue sensory function in the lower central area.
      METHODS: All positron emission tomography (PET) clinical activation studies
      performed over a 3-year period at the Montreal Neurological Institute and
      Hospital were evaluated by coregistering the PET images with three-dimensional
      reconstructions of magnetic resonance images obtained in the same patients. In
      addition to stereotactic coordinates and measurements based on distance from the
      sylvian fissure, gyral and sulcal landmarks were analyzed to determine their
      reliability in localizing the sensory areas of the tongue and lower face. The
      convolutional anatomy of the central area is an important guide to the
      identification of function. The sensory area of the tongue is recognized as a
      triangular region at the base of the postcentral gyrus; the sensory area of the
      lower face resides in the narrowed portion of the postcentral gyrus, immediately
      above the tongue area. CONCLUSIONS: Cortical landmarks such as the substrata of
      tongue and face sensory impressions are more reliable guides than stereotactic
      coordinates or measurements for localizing function.

PMID- 12186468
TI  - A novel fibroblast growth factor receptor 2 mutation in Crouzon syndrome
      associated with Chiari type I malformation and syringomyelia.
AB  - OBJECT: It has been reported that due to premature synostosis of the lambdoid
      suture in the first 24 months of life, more than 70% of patients with Crouzon
      syndrome concurrently suffer from chronic tonsillar herniation (Chiari Type I
      malformation) and some (20%) associated syringomyelia. The goal of the present
      study was to examine mutations in the fibroblast growth factor receptor (FGFR)
      genes in Crouzon syndrome and its related conditions. METHODS: Five patients were
      studied: three with Crouzon syndrome (one sporadic and two familial), one with
      sporadic Chiari I with syringomyelia, and one with unilateral lambdoid
      synostosis. Deoxyribonucleic acid was screened for FGFR1-3 mutations by using
      single-strand conformational polymorphism and subsequent direct sequencing. Two
      types of missense mutations were detected in the FGFR2 gene, Cys342Trp (1205, TGC
      --> TGG) in a patient with sporadic Crouzon syndrome and Tyr281Cys (1021, TAC -->
      TGC) in two siblings (brother and sister) with familial Crouzon syndrome,
      respectively. The former has been reported only in sporadic cases but the latter
      has not previously been identified. A polymorphism in the FGFR3 gene, Asn294Asn
      (882, AAT --> AAC), was also detected in three patients. No mutation was found in
      the patient with sporadic Chiari I with syringomyelia. CONCLUSIONS: The FGFR2
      missense mutation was detected in Crouzon syndrome but not in sporadic Chiari I
      with syringomyelia or lambdoid synostosis. A novel FGFR2 mutation, Tyr281Cys, was
      found in familial Crouzon syndrome with Chiari I and syringomyelia. It may be
      informative to look for this in patients with Crouzon syndrome and associated
      syringomyelia.

PMID- 12186469
TI  - Volumetric quantification of Fisher Grade 3 aneurysmal subarachnoid hemorrhage: a
      novel method to predict symptomatic vasospasm on admission computerized
      tomography scans.
AB  - OBJECT: Predicting which patients with aneurysmal subarachnoid hemorrhage (SAH)
      will develop delayed ischemic neurological deficit (DIND) due to vasospasm
      remains subjective and unreliable. The authors analyzed the utility of a novel
      software-based technique to quantify hemorrhage volume in patients with Fisher
      Grade 3 aneurysmal SAH. METHODS: Patients with aneurysmal SAH in whom a
      computerized tomography (CT) scan was performed within 72 hours of ictus and
      demonstrated Fisher Grade 3 SAH were analyzed. Severe DIND was defined as new
      onset complete focal deficit or coma. Moderate DIND was defined as new onset
      partial focal deficit or impaired consciousness without coma. Fifteen consecutive
      patients with severe DIND, 13 consecutive patients with moderate DIND, and 12
      consecutive patients without DIND were analyzed. Software-based volumetric
      quantification was performed on digitized admission CT scans by a single examiner
      blinded to clinical information. There was no significant difference in age, sex,
      admission Hunt and Hess grade, or time to admission CT scan among the three
      groups (none, moderate, or severe DIND). Patients with severe DIND had a
      significantly higher cisternal volume of hemorrhage (median 30.5 cm3) than
      patients with moderate DIND (median 12.4 cm3) and patients without DIND (median
      10.3 cm3; p < 0.001). Intraparenchymal hemorrhage and intraventricular hemorrhage
      were not associated with DIND. All 13 patients with cisternal volumes greater
      than 20 cm3 developed DIND, compared with 15 of 27 patients with volumes less
      than 20 cm3 (p = 0.004). CONCLUSIONS: The authors developed a simple and
      potentially widely applicable method to quantify SAH on CT scans. A greater
      volume of cisternal hemorrhage on an admission CT scan in patients with Fisher
      Grade 3 aneurysmal SAH is highly associated with DIND. A threshold of cisternal
      hemorrhage volume (> 20 cm3) may exist above which patients are very likely to
      develop DIND. Prospective application of software-based volumetric quantification
      of cisternal SAH may predict which patients will develop DIND.

PMID- 12186470
TI  - Expression of members of the calcium-binding S-100 protein family in a rat model
      of cerebral basilar artery vasospasm.
AB  - OBJECT: The aim of this study was to investigate the role of S-100 proteins in
      the onset of vasospasm induced by subarachnoid hemorrhage (SAH), which leads to
      severe neurological morbidity and death. It has recently been argued that
      modifications in the levels of expression of some intracellular signaling
      elements controlling the organization of the actin cytoskeleton (including the
      rho A small guanosine triphosphatase and its related kinases) play significant
      roles in the induction of smooth-muscle cell contraction, a calcium-dependent
      process that is pathognomonic of SAH-induced vasospasm at the molecular level.
      Several members of the calcium-binding S-100 protein family are known to exercise
      significant control over the organization of the actin cytoskeleton. METHODS: The
      levels of expression of S-100 proteins in SAH-induced vasospasm have never been
      investigated. The authors therefore used a double-hemorrhage rat model of SAH
      induced vasospasm to determine whether the levels of expression of S-100B, S
      100A1, S-100A2, S-100A4, and S-100A6 proteins on immunohistochemical studies were
      significantly modified in this pathological condition. Quantitative determination
      of immunohistochemically confirmed expression of S-100 proteins (accomplished
      with the aid of computer-assisted microscopy) revealed that SAH-induced vasospasm
      is accompanied by a very significant increase in S-100B, S-100A2, and, to a
      lesser extent, in S-100A4 and S-100A6 expression, whereas this condition is not
      accompanied by significant modifications to S-100A1 expression. CONCLUSIONS: Such
      significant modifications in the levels of expression of different members of the
      S-100 protein family in SAH-induced vasospasm could relate to the various roles
      played by this specific class of calcium-binding proteins at the level of actin
      cytoskeleton organization. These modifications in S-100 protein expression seem
      relatively specific to SAH-induced vasospasm, because heparin-induced epilepsy
      like symptoms were accompanied by dramatically distinct profiles of S-100 protein
      expression.

PMID- 12186471
TI  - Role of magnesium in the reduction of ischemic depolarization and lesion volume
      after experimental subarachnoid hemorrhage.
AB  - OBJECT: Ischemia-induced tissue depolarizations probably play an important role
      in the pathophysiology of cerebral ischemia caused by parent vessel occlusion.
      Their role in ischemia caused by subarachnoid hemorrhage (SAH) remains to be
      investigated. The authors determined whether ischemic depolarizations (IDs) or
      cortical spreading depressions (CSDs) occur after SAH, and how these relate to
      the extent of tissue injury measured on magnetic resonance (MR) images. In
      addition, they assessed whether administration of MgSO4 reduces depolarization
      time and lesion volume. METHODS: By means of the endovascular suture model,
      experimental SAH was induced in 52 rats, of which 37 were appropriate for
      analysis, including four animals that underwent sham operations. Before induction
      of SAH, serum Mg++ levels were measured and 90 mg/kg intravascular MgSO4 or
      saline was given. Extracellular direct current potentials were continuously
      recorded from six Ag/AgCl electrodes, before and up to 90 minutes following SAH,
      after which serum Mg++ levels were again measured. Next, animals were transferred
      to the MR imaging magnet for diffusion-weighted (DW) MR imaging. Depolarization
      times per electrode were averaged to determine a mean depolarization time per
      animal. No depolarizations occurred in sham-operated animals. Ischemic
      depolarizations occurred at all electrodes in all animals after SAH. Only two
      animals displayed a single spreading depression-like depolarization. The mean
      duration of the ID time was 41 +/- 25 minutes in the saline-treated controls and
      31 +/- 30 minutes in the Mg++-treated animals (difference 10 minutes: p = 0.31).
      Apparent diffusion coefficient (ADC) maps of tissue H2O, obtained using DW images
      approximately 2.5 hours after SAH induction, demonstrated hypointensities in both
      hemispheres, but predominantly in the ipsilateral cortex. No ADC abnormalities
      were found in sham-operated animals. The mean lesion volume, as defined on the
      basis of a significant ADC reduction, was 0.32 +/- 0.42 ml in saline-treated
      controls and 0.11 +/- 0.06 ml in Mg++-treated animals (difference 0.21 ml; p =
      0.045). Serum Mg++ levels were significantly elevated in the Mg++-treated group.
      CONCLUSIONS: On the basis of their data, the authors suggest that CSDs play a
      minor role, if any, in the acute pathophysiology of SAH. Administration of Mg++
      reduces the cerebral lesion volume that is present during the acute period after
      SAH. The neuroprotective value of Mg++ after SAH may, in part, be explained by a
      reduction in the duration of the ID of brain cells.

PMID- 12186472
TI  - Anatomical analysis of different hemispherotomy procedures based on dissection of
      cadaveric brains.
AB  - OBJECT: Functional hemispherectomy, itself a modification of anatomical
      hemispherectomy, has been further modified to a less invasive method
      (hemispherotomy), in which cortical resection is minimized and the rest of the
      affected hemisphere is functionally isolated by transecting its projection and
      commissural fibers. Although descriptions of three different types of
      hemispherotomy procedures have been published, the authors believe that it is
      important to develop a common and universally acceptable method based on a
      systematic analysis of topographic anatomy and neuronal connections. To this end,
      they have analyzed the three aforementioned procedures on the basis of meticulous
      fiber dissections in previously frozen formalin-fixed human brains. METHODS: The
      brain anatomy pertinent to surgical hemispherotomy is described in conjunction
      with dissection studies in 14 previously frozen, formalin-fixed human brains. The
      anatomical landmarks necessary for performing particular neuronal fiber
      resections are identified, and their relationships with operative methods are
      discussed, with an emphasis on commonalities among the three hemispherotomy
      procedures. CONCLUSIONS: In this analysis the authors confirmed that
      hemispherotomy typically consists of four common procedures: 1) interruption of
      the internal capsule and corona radiata; 2) resection of the medial temporal
      structures; 3) transventricular corpus callosotomy; and 4) disruption of the
      frontal horizontal fibers. After meticulous dissection of cadavers, the authors
      have designated a reliable method for performing these four operations that may
      be applicable as a commonly used procedure.

PMID- 12186473
TI  - Failure of B7.1-modified tumor to evoke full activation of CD8+ tumor
      infiltrating lymphocytes in the central nervous system: prevention of parental
      tumor growth in the subcutaneous environment.
AB  - OBJECT: It is well known that the central nervous system (CNS) is an
      immunologically privileged site. To characterize CD8+ tumor-infiltrating
      lymphocytes (TILs) recovered from the CNS, the authors compared these cells with
      TILs recovered from subcutaneous tissue by using a B7.1 gene-modified tumor
      implantation model. METHODS: The authors established a B7.1 gene-modified EL4
      murine lymphoma cell line (EL4-B7.1) and implanted the cells into the CNS to
      observe the duration of tumor-free survival. Although EL4-B7.1 cells were
      completely rejected in a subcutaneous implantation model, 40% of animals died
      after the CNS implantation (all animals in which the parent tumor was implanted
      died within 16 days). Therefore, the authors isolated TILs from each implantation
      site and analyzed the expressions of activation antigens CD25 and CD69 by
      performing the anti-CD8 magnetic beads separation method and flow cytometric
      analysis. After implantation of the parent tumor, there was no difference in the
      number of TILs from each site (CD25 1.7-3.2%, CD69 21.9-34.3%). After
      implantation of the B7.1-modified tumor, the CD25-expressing TIL population from
      the subcutaneous site was 4.68 times higher than that from the CNS site (17.8%
      compared with 3.8%). Based on these findings, the authors used a mitomycin C
      treated EL4-B7.1 subcutaneous vaccination with various protocols. Vaccination
      before tumor challenge was sufficient to prevent the development of the tumor.
      For animals with established tumor, the vaccination protocol was able to prolong
      host survival (p = 0.0053). CONCLUSIONS: The data clearly demonstrate that the
      CNS environment fails to activate CD8+ TILs fully. These are the first data
      indicating in detail a difference between CD8+ TILs from the CNS and those from
      other sites based on a B7.1-modified tumor model.

PMID- 12186475
TI  - Epileptiform activity extinguished by amygdala infusion of the neurotoxin
      ibotenate in a rat model of temporal lobe epilepsy.
AB  - OBJECT: The long-term antiseizure effects of local convection-enhanced infusion
      of the excitotoxin ibotenate were examined in a rat model of temporal lobe
      epilepsy. METHODS: A single injection of kainate, an epileptogenic excitatory
      amino acid, into the left amygdala elicited chronic spontaneous recurrent seizure
      activity for at least 36 days after the injection. Two weeks after the injection,
      infusion of ibotenate, a nonepileptogenic excitatory amino acid that is an axon
      sparing neuronal cell toxin, into the left amygdala and piriform lobe induced
      immediate and permanent extinction of electrical and behavioral seizure activity.
      CONCLUSIONS: Lesioning of an epileptic focus by convective distribution of
      ibotenate can produce an enduring suppression of seizure activity, indicating a
      chemical neurosurgical approach for epilepsy therapy.

PMID- 12186474
TI  - Gene therapy for meningioma: improved gene delivery with targeted adenoviruses.
AB  - OBJECT: Due to their surgical inaccessibility or aggressive behavior, some
      meningiomas cannot be cured with current treatment strategies. Gene therapy is an
      emerging strategy for the treatment of brain tumors, which the authors
      investigated to determine whether adenoviruses could be used for gene transfer in
      meningioma cells. METHODS: The presence of the high-affinity Coxsackievirus and
      adenovirus receptor (CAR) for adenovirus type 5, as well as endothelial growth
      factor receptor (EGFR) and alpha, integrins (ITGAVs), were analyzed in primary
      tumors by using immunohistochemical studies and in primary meningioma cell
      cultures by using fluorescence-activated cell sorting. Targeting of adenoviruses
      to EGFR was achieved using bispecific antibodies, whereas targeting of
      adenoviruses to the ITGAVs was accomplished by insertion of an RGD (arginine
      glycine-aspartic acid) motif in the adenovirus fiber H1 loop. Gene transfer
      efficiency of untargeted and targeted vectors was compared in primary cell
      cultures and in spheroids derived from patients' resected tumor material. The
      presence of CARs was observed in all tumors and in all but one of the derived
      primary meningioma cells. The higher expression of EGFRs and ITGAVs indicated
      that these receptors could be used as alternative targets to redirect the
      adenoviruses. Redirection of adenoviruses to the EGFRs or integrins enhanced gene
      transfer threefold (range two-sevenfold) for EGFRs in primary meningioma cells
      and ninefold (range three-23-fold) for integrins (p = 0.002, analysis of
      variance). The effect of adenovirus targeting was confirmed in spheroids composed
      of primary meningioma cells. CONCLUSIONS: Gene transfer with adenoviruses
      targeted to tumor-specific receptors is very effective in primary meningioma
      cells and spheroids. These vectors are promising agents for gene therapy of
      meningiomas.

PMID- 12186476
TI  - Spontaneous intracerebral hematomas expanding during the early stages of
      hemorrhage without rebleeding. Report of three cases.
AB  - Expansion of intracerebral hematoma usually occurs in the chronic phase because
      of repeated bleeding from pre-existing vascular anomalies or exudation of blood
      from capillaries of the capsule. In contrast, spontaneous intracerebral hematoma
      expanding during the acute phase of hemorrhage without rebleeding is seldom seen.
      Three such cases are reported, along with magnetic resonance (MR) and
      computerized tomography (CT) follow-up studies. The follow-up MR images and CT
      scans demonstrated no evidence of rebleeding, but revealed gradual expansion of a
      fluid component of the hematoma, beginning in the acute phase. Volume alterations
      posthemorrhage are carefully documented. There was a characteristic phenomenon of
      layering, with the red blood cell component of the clot settling by gravity and
      the serum separating as well as seen in a test tube, depending on whether a
      preservative was used. Examination of blood samples indicated a possible
      correlation between expansion of the hematoma and the activities of both the
      fibrinolytic system and coagulation factors.

PMID- 12186477
TI  - Camptocormia treated with bilateral pallidal stimulation.
AB  - The authors report the neurological, neurophysiological, and neuropsychological
      effects of using long-term bilateral pallidal high-frequency deep brain
      stimulation (DBS) in a case of disabling camptocormia. Deep brain stimulation
      electrodes were implanted stereotactically to target the globus pallidus internus
      (GPi) bilaterally. Local field potentials (FPs) were recorded using the DBS
      electrodes and concurrent abdominal flexor electromyography (EMG) potentials
      during camptocormic episodes. Videotaped assessments of the movement disorder and
      neuropsychological evaluations of the patient before implantation and 6 months
      after initiation of pallidal stimulation were recorded. There was significant
      functional improvement following long-term pallidal stimulation, and some
      improvement was noted in neuropsychological scores. A temporal correlation
      between the GPi FPs and EMG-recorded rectus abdominis potentials was evident.
      There were no treatment-related adverse effects. The authors have found that long
      term pallidal stimulation was safe and offered functional benefit to a patient
      with this severely disabling condition. The physiological studies may help
      further the understanding of the pathophysiology of this rare entity.

PMID- 12186479
TI  - Carpal tunnel syndrome caused by thrombosis of the median artery: the importance
      of high-resolution ultrasonography for diagnosis. Case report.
AB  - The rare case of a patient with carpal tunnel syndrome caused by thrombosis of a
      persistent median artery is presented. Progressive pain in the wrist and
      dysesthesias in the third and fourth fingers were the atypical complaints. High
      resolution ultrasonography revealed a bifid median nerve that was compressed by
      an occluded median artery. The intraoperative findings are described, and
      emphasis is placed on the importance of using high-resolution ultrasonography for
      presurgical diagnosis.

PMID- 12186478
TI  - Galenic dural arteriovenous fistula: unusual clinical presentation and successful
      endovascular therapy. Case report.
AB  - The authors report a case in which the clinical and neuroimaging findings were
      initially considered diagnostic of a brainstem glioma. Angiography revealed a
      deep venous system (galenic) dural arteriovenous fistula causing brainstem
      interstitial edema. Successful endovascular surgery resulted in complete clinical
      recovery of the patient and resolution of the structural abnormalities that had
      been observed on magnetic resonance images. The neuroimaging and therapeutic
      significance of this case are discussed.

PMID- 12186480
TI  - A graft-versus-tumor effect in a patient with ependymoma who received an
      allogenic bone marrow transplant for therapy-related leukemia. Case report.
AB  - Graft-versus-leukemia effect is an immune-mediated antitumor phenomenon
      associated with allogenic bone marrow transplants (BMTs) for hematological
      malignancies, and recent findings have indicated that a similar effect could
      occur in some solid tumors such as breast cancers. The authors report on a 42
      year-old man with a recurrent ependymoma who received an allogenic BMT for
      therapy-related leukemia. After transplantation, the patient developed chronic
      graft-versus-host disease, which was controlled with steroid agents.
      Interestingly, the recurrent ependymoma regressed steadily over the next 21
      months posttransplant, until the tumor became almost undetectable on magnetic
      resonance images. This case indicates that the graft-versus-tumor effect,
      mediated by cytotoxic T cells, may be able to target intraparenchymal
      neuroepithelial tumors, despite the brain's generally recognized status as an
      immunoprivileged organ.

PMID- 12186481
TI  - Choriocarcinoma brain metastasis in a patient with viable intrauterine pregnancy.
      Case report.
AB  - The authors report the case of a woman who presented during her 30th week of
      pregnancy with a large brain metastasis from a previously undetected metastatic
      choriocarcinoma. The metastasis caused significant neurological deficit due to
      mass effect, necessitating rapid intervention. Medical management included a
      regimen of high-dose corticosteroid medications for 36 hours, followed by
      cesarean delivery of the fetus and craniotomy to remove the metastatic tumor,
      chemotherapy and radiation therapy were begun within 1 week postsurgery. Both the
      baby and mother survived, and as of the 1-year follow-up examination, there was
      no evidence of disease in the mother. This is only the second report of a
      metastatic choriocarcinoma associated with a simultaneous viable intrauterine
      pregnancy, and the only case in which surgical removal of a brain metastasis was
      required. Coordinated multidisciplinary treatment of mother and fetus by members
      of the neurosurgery, medical oncology, neonatology, and obstetrics services
      facilitated a good outcome in this case.

PMID- 12186482
TI  - Hemifacial spasm associated with an ependymal cyst in the cerebellopontine angle.
      Case report.
AB  - No previous case of hemifacial spasm associated with an ependymal cyst has been
      reported in the literature. In this article the authors report the first case in
      which hemifacial spasm accompanied an ipsilateral cerebellopontine angle
      ependymal cyst in a 27-year-old woman. Cyst fenestration and arterial
      decompression of the facial nerve at the root exit zone resulted in complete
      resolution of the patient's symptoms. A histopathological study including
      immunohistochemical methods identified an ependymal cyst.

PMID- 12186483
TI  - Intracranial-to-intracranial vascular anastomosis created using a
      microanastomotic device for the treatment of distal middle cerebral artery
      aneurysms. Technical note.
AB  - The use of a microanastomotic device for direct connection of intracranial
      vessels can be helpful to facilitate removal of distally located middle cerebral
      artery (MCA) aneurysms. The authors report on two patients who presented for
      treatment with large aneurysms distally located on the MCA. The aneurysms were
      completely excised and the proximal and distal portions of the parent vessel were
      connected in an end-to-end fashion by using a microanastomotic device. The time
      required to crossclamp the vessel for excision of the aneurysm and primary
      anastomosis was 10 minutes in one case and 15 minutes in the other. The short
      crossclamp time and high-quality anastomosis afforded by this device may be
      useful in the treatment of these difficult lesions and the prevention of cerebral
      ischemia.

PMID- 12186484
TI  - Magnetic resonance imaging/spectroscopy of an intraaxial epidermoid: similarity
      to an abscess. Case illustration.

PMID- 12186485
TI  - Perisylvian frontotemporal hematoma due to rupture of an anterior communicating
      artery aneurysm. Case illustration.

PMID- 12186487
TI  - Psychosurgery.

PMID- 12186486
TI  - Epidural hematoma and muscle calcification after encephalomyosynangiosis. Case
      illustration.

PMID- 12186488
TI  - Neural transplant.

PMID- 12186489
TI  - Remote cerebellar hemorrhage.

PMID- 12186490
TI  - Between dad and son: initiating, delivering, and assimilating bad cancer news.
AB  - The opening moments of a phone call reveal how a father informs his son, for the
      1st time, that his mom's tumor is malignant. An extended phone opening reveals
      how delaying talk about the mom's condition allows for important interactional
      work: Displaying resistance to announce the bad news directly, projecting and
      anticipating the valence of forthcoming news prior to its announcement, and
      delicately sharing ownership of a serious health condition at the outset of a
      family cancer journey. Enacting a biomedical demeanor, replete with technical
      language and withholdings of emotional and personal reactions, subsequent
      delivery and reception of the bad news is managed stoically-a normalized resource
      employed by consequential figures when managing and coping with dreaded news
      events. By closely examining how family members talk through cancer on the
      telephone, the scope of health communication research is extended beyond clinical
      settings into home environments, progress is made on the noticeable absence of
      interactional studies in psycho-oncology, and diverse implications arise for
      understanding how lay persons diagnose and manage illness dilemmas.

PMID- 12186491
TI  - Presenting the problem in pediatric encounters: "symptoms only" versus "candidate
      diagnosis" presentations.
AB  - This article examines 2 practices that are used to present children's problems to
      their pediatricians in acute care encounters. Using the methodology of
      conversation analysis, this article examines the alternative stances embodied by
      problem presentations, which offer "symptoms only" versus problem presentations,
      which also include a "candidate diagnosis." This article suggests that parents
      who offer only symptoms in their problem presentations are hearable as adopting a
      stance that they are primarily seeking medical evaluations of their children. By
      contrast, a parent who includes a candidate diagnosis of the problem is hearable
      as adopting a stance that he or she is seeking confirmation of the diagnosis and
      treatment for that illness condition. This communication practice may be treated
      by physicians as placing pressure on them to prescribe treatment-in particular
      antibiotic treatment. The implications of this are discussed.

PMID- 12186492
TI  - Physician-patient co-construction of illness narratives in the medical interview.
AB  - Researchers and medical educators in the area of physician-patient communication
      encourage physicians to elicit patient narratives during medical encounters to
      facilitate data collection, rapport building, and patient satisfaction. These
      scholars, however, provide little information about the nature of the narrative,
      especially in the context of the medical interview. This article reviews the
      multidisciplinary literature on narrative and reports the results of a narrative
      analysis of 21 physician-patient interviews. A set of criteria for defining
      narrative is derived from the literature and applied to these interviews,
      demonstrating the limitations of previous conceptions of narrative and suggesting
      an expanded definition. This expansion emphasizes the notion that narratives are
      co-constructed through the interaction of both participants in the conversation
      in which they occur. Application of the expanded definition to the same
      interviews reveals 3 new narrative forms: narratives that emerge through the co
      constructed chronology of key events, the co-constructed repetition and
      elaboration of key events, and the coconstructed interpretation of the meaning of
      key events.

PMID- 12186493
TI  - A double standard in bioethical reasoning for disclosure of advanced cancer
      diagnoses in Japan.
AB  - This article examines the Japanese double standard in bioethical reasoning with
      respect to disclosure of advanced cancer diagnoses. This article is devoted to
      the analysis of communication styles preferred among the Japanese across
      different hypothetical situations involving cancer as one's own illness as
      opposed to cancer as a family member's illness. Generally, the Japanese prefer
      the use of a direct communication style, involving disclosure of the true
      diagnosis for their own cancer. When cancer is a family member's illness,
      however, many Japanese perceive the use of an indirect communication style,
      involving no disclosure or ambiguous disclosure to the patient more ethical than
      direct communication of the diagnosis. This article explores how and why the
      Japanese use this double standard when making judgments about the morality of
      disclosing an advanced cancer diagnosis to the patient. Policy and educational
      implications for reconciling such a double standard in bioethical reasoning for
      cancer disclosure are discussed as conclusions.

PMID- 12186494
TI  - Women's perceptions of the risks of age-related diseases, including breast
      cancer: reports from a 3-year research study.
AB  - Misperceptions of health risks lead many women to misunderstand their risks and
      fail to take appropriate measures to prevent or treat many diseases. This article
      analyzes the impact of various sources of information on the perceptions and
      misperceptions of women regarding the risks of age-related diseases. This article
      shows that most of the women respondents held incorrect beliefs about their risk
      of heart disease, breast and lung cancer, and osteoporosis; half held inaccurate
      beliefs about disease-related statistical correlation and causation, and about
      dose-response relations; and many lacked the skills necessary to evaluate media
      reports about health and medicine. This article indicates that information and
      education related to health issues, focused on improved public understanding and
      decision making related to health risks, is needed to achieve improved health
      outcomes.

PMID- 12186495
TI  - X-ray crystal structure of a monoclonal antibody that binds to a major
      autoantigenic epitope on thyroid peroxidase.
AB  - Thyroid peroxidase (TPO) catalyzes the production of thyroid hormones and is a
      major autoantigen in autoimmune thyroid disease (AITD). It is believed that the
      majority of TPO autoantibodies bind to an immunodominant region consisting of two
      overlapping domains. Precise location of these domains would help our
      understanding of the interaction between TPO and TPO autoantibodies. 4F5 is a
      mouse monoclonal antibody (IgG1, kappa) that reacts with high affinity (2.6 x
      10(10) mol/L(-1)) with one of the major autoantigenic regions on TPO. Heavy chain
      genes of 4F5 were from the VH1 germline gene family, germline genes for the D
      region could not be assigned and the J region was from the JH2 germline. Light
      chain genes were from Vkappa4/5 and Jkappa2, germline gene families. The Fab
      fragment of 4F5 was prepared by papain digestion, purified, crystallized, and the
      structure solved to 1.9 A using molecular replacement. The refined structure had
      an R factor of 19.5% and a free R factor of 23.9%. Deduced amino acid sequence
      and amino acid sequence obtained from diffraction analysis were compared and used
      to finalize the 4F5 Fab model. Structural analysis indicated that the structure
      of 4F5 is that of a standard Fab and its combining site is flat and is rich in
      tyrosine residues. Comparison of the structure of 4F5 with that of a TPO
      autoantibody Fab, TR1.9 suggests that the two antibodies are unlikely to
      recognise the same structures on TPO.

PMID- 12186496
TI  - Expression of eukaryotic translation initiation factors 4E and 2alpha correlates
      with the progression of thyroid carcinoma.
AB  - Cell growth and proliferation depend on protein synthesis that is regulated, in
      part, by two eukaryotic translation initiation factors, eIF-4E and eIF-2alpha.
      These factors are transiently increased as normal cells respond to growth factors
      and are constitutively elevated in transformed cells. In cultured cells, eIF-4E
      facilitates cell cycle progression by increasing the expression of cell cycle
      promoting proteins including cyclin D1. Our previous study revealed elevated
      cyclin D1 expression in histologically more aggressive thyroid carcinomas as
      compared to conventional papillary carcinoma. We hypothesized that the increased
      cyclin D1 expression might correlate with increased eIF-4E expression. We,
      therefore studied the expression of eIF-4E by immunohistochemistry in 25 cases of
      conventional papillary carcinoma (CPC) and 28 cases of aggressive thyroid
      carcinomas (ATC), the latter included 11 tall cell/columnar cell variant of
      papillary carcinoma, 5 insular carcinomas, and 12 anaplastic carcinomas. We also
      analyzed the expression of eIF-2a in the same samples as this factor is usually
      regulated similarly to eIF-4E in cell culture models. Of the 25 CPC, 13 were eIF
      4E positive (11 weakly and 2 strongly), and 19 were eIF-2a positive (14 weakly
      and 5 strongly). Conversely, of the 28 ATC, 25 were eIF-4E positive (4 weakly and
      21 strongly), and 23 were eIF-2alpha positive (4 weakly and 19 strongly). There
      was a significantly increased expression of both eIF-4E (p < 0.001) and eIF
      2alpha (p < 0.001) in ATC compared to CPC, suggesting that these translation
      initiation factors may play a role in the progression of thyroid cancer.

PMID- 12186497
TI  - Medullary carcinomas of the thyroid: a monoclonal origin.
AB  - We studied the clonality of medullary thyroid carcinomas (MTC) from 16 female
      patients by determining X chromosome inactivation by polymerase chain reaction
      (PCR) amplification of a CAG repeat in exon 1 of the human androgen-receptor
      gene. One patient with sporadic medullary thyroid carcinoma (MTC) was homozygous
      for this microsatellite and was not considered for the assessment of clonality.
      Sixteen tumor samples from the informative 15 patients were studied: 11 were from
      sporadic cases and 5 were from familial cases (3 cases of multiple endocrine
      neoplasia type 2A [MEN 2A]; 1 case of familial medullary thyroid carcinoma
      [FMTC]). Fourteen tumor samples (10/11 sporadic, 3/4 MEN 2A and 1/1 FMTC) were
      clearly monoclonal with allelic cleavage ratios between 2.5 and 49.1. Sixty-four
      percent of these cases (9/14) had the preferential amplification of the shorter
      allele while 36 percent (5/14) had the preferential amplification of the longer
      allele. Two frozen tumor samples (1 sporadic and 1 MEN 2A) were polyclonal.
      However, the corresponding tumor embedded in paraffin from the sporadic case was
      monoclonal. The other polyclonal tumor was found in the right thyroid lobe of a
      patient with MEN 2A who had a monoclonal tumor in the left lobe. Our results
      clearly demonstrate that MTC have a monoclonal origin in the majority of the
      cases.

PMID- 12186498
TI  - Serum levels of tumor necrosis factor-alpha, soluble intercellular adhesion
      molecule-1, soluble vascular cell adhesion molecule-1, and soluble interleukin-1
      receptor antagonist in patients with thyroid eye disease undergoing treatment
      with somatostatin analogues.
AB  - The aim of this prospective, randomized study was to investigate the serum levels
      of tumor necrosis factor-alpha (TNF-alpha), soluble intercellular adhesion
      molecule-1 (sICAM-1), soluble vascular cell adhesion molecule-1 (sVCAM-1), and
      soluble interleukin-1 receptor antagonist (sIL-1RA) in patients with thyroid eye
      disease (TED) before and 1 and 3 months after treatment with somatostatin
      analogues (SM-a). Thirty patients, all with signs and symptoms of TED, were
      studied. Twenty-two patients (13 females) had active eye disease with a clinical
      activity score (CAS) > or = 4 (patients with active disease [PA]) and 8 patients
      (5 females) had inactive TED with CAS < or = 3 (patients with inactive disease
      [PI]). All PA patients had a positive orbital octreoscan, whereas PI patients had
      a negative one. Fifteen patients from the PA group were selected randomly and
      received SM-a (PA-S subgroup), while the remaining 7 patients were used as
      control subgroup (PA-C), received neither therapy, nor placebo. From the 15
      patients who received SM-a (PA-S), 6 received octreotide (OCT) and 9 lanreotide
      (LRT). TED was reevaluated using the CAS 1 and 3 months after the initiation of
      SM-a treatment. Ten healthy individuals (6 females) were used as controls (group
      C). We found an increase in the basal levels of TNF-alpha (14.2 +/- 7.1 pg/mL),
      sICAM-1 (809.1 +/- 167.0 ng/mL), and sIL-1RA (542.1 +/- 259.0 pg/mL) in PA
      patients as a total group compared with the PI (1.6 +/- 1.9, 676.8 +/- 73.4,
      267.6 +/- 152.8, respectively) group and C (1.9 +/- 1.4, 598.0 +/- 126.2, 258.6
      +/- 155.1, respectively). The basal levels of TNF-alpha (13.3 +/- 8.3 pg/mL) and
      sIL-1RA (533.7 +/- 308.9 pg/mL) in PA-S as well as in PA-C (16.0 +/- 2.9, 560.2
      +/- 107.3, respectively) subgroups were also increased compared with PI patients
      and C (1.9 +/- 1.4 and 258.6 +/- 155.1, respectively). The same was true for
      sICAM-1 when baseline levels compared with C (817.1 +/- 187.3 and 791.9 +/-
      123.5, respectively vs. 598.0 +/- 126.2 ng/mL). After SM-a, serum levels of sICAM
      1 and sVCAM-1 were decreased significantly 1 (781.2 +/- 205.9, 1,193.5 +/- 511.8
      ng/mL) and 3 months (786.8 +/- 199.6, 1,122.1 +/- 225.3 ng/mL) after the
      initiation of treatment. In conclusion, serum levels of TNF-a, sICAM-1, and sIL
      1RA were elevated in patients with active TED compared to controls. Furthermore,
      sICAM-1 and sVICAM-1 levels declined during the treatment with SM-a in patients
      with active TED.

PMID- 12186499
TI  - Antithyrotropin receptor antibody: an update.
AB  - Numerous studies have reported the characteristics and significance concerning
      antithyrotropin receptor antibodies (TSHR-Abs), which cause Graves' disease and
      in some cases primary hypothyroidism. However, many unsolved questions concerning
      those antibodies remain. Here, recent developments in the study of TSHR-Abs are
      reviewed based on three aspects: mechanisms of TSHR-Ab production, antibody
      binding epitopes, and clinical TSHR-Ab assays. Mechanisms of TSHR-Ab production
      are discussed from five points of view: aberrant expression of the major
      histocompatibility complex, dysregulation of T cells, molecular mimicry,
      bystander effect, and expansion of autoreactive B cells. Regarding epitopes,
      unique TSHR-Abs have been reported that may explain the complicated
      pathophysiology of patients with TSHR-Ab diseases. Finally, recent efforts to
      improve TSHR-Ab measurements are introduced. Such efforts will contribute to
      clinical examinations and treatments for thyroid diseases as well as experimental
      methods of thyroidology.

PMID- 12186500
TI  - Differentiated thyroid carcinoma: a polygenic disease.
AB  - Differentiated thyroid cancer is a rare disease and until recently was considered
      to be sporadic. However, increasing evidence has been found for a genetic basis
      of this disease. In approximately 5% of patients the differentiated thyroid
      cancer is dominantly inherited. Several families with different syndromes, of
      which differentiated thyroid cancer is a feature, have already been described.
      However, until now, single genes explain only a minority of cases. We hypothesize
      that differentiated thyroid cancer is a polygenic disease. Data from
      epidemiologic studies, about occult and multifocal carcinomas and the different
      response to specific risk factors contribute to this hypothesis.

PMID- 12186501
TI  - Iodine deficiency in Azerbaijan after the discontinuation of an iodine
      prophylaxis program: reassessment of iodine intake and goiter prevalence in
      schoolchildren.
AB  - The goal of this study was to assess the prevalence of iodine deficiency (ID) in
      Azerbaijan after the discontinuation of an iodine prophylaxis program by
      assessing the prevalence of goiter, iodine intake, and thyroid function. The
      study included 942 schoolchildren (475 boys and 467 girls) ages 8-14 years, from
      13 distinct regions. The survey included the following: (1) clinical evaluation;
      (2) assessment of thyroid volume both by ultrasound and by palpation; (3)
      determination of iodide in a morning urine specimen using the classic Sandel
      Kolthoff reaction in 347 schoolchildren; (4) determinations of thyrotropin (TSH),
      triiodothyronine (T3), thyroxine (T4), thyroglobulin (Tg), and anti-thyroid
      peroxidase (TPO) in serum (n = 165) and TSH in whole blood spotted on filter
      paper (n = 942). The prevalence of goiter for the whole country was determined by
      ultrasound (US) to be 86% and by palpation 66%, reaching 100% in the mountainous
      regions of Caucasus. The median urinary iodine excretion (UIE) was 54 microg/L,
      reaching level of 26 and 39 microg/L in the Caucasus region. In conclusion,
      according to the World Health Organization (WHO) classification, Azerbaijan now
      has mild to moderate ID (median UIE, 54 microg/L) and in the mountainous regions
      with severe ID. The high prevalence of goiter and the low UIE emphasizes the need
      for urgent medical reintervention. An iodination program is now implemented by
      our team in the mountainous regions under the auspice of the government of
      Azerbaijan.

PMID- 12186502
TI  - Nondiagnostic thyroid fine-needle aspiration cytology: management dilemmas.
AB  - Approximately 10% to 20% of thyroid biopsies by fine-needle aspiration (FNA) are
      nondiagnostic. The management of thyroid nodules in which FNA is nondiagnostic
      remains controversial because few studies have addressed this issue. We
      retrospectively reviewed the medical records of 153 patients with nondiagnostic
      FNAs of the thyroid performed in 1994. Sixty patients had reaspiration biopsies
      performed. Thirty-seven specimens (62%) were diagnostic and 23 (38%) remained
      nondiagnostic. Of the 27 patients who had a thyroid operation, 10 (37%) had a
      malignancy. Preoperative information about physical examination, ultrasound
      imaging, or nondiagnostic FNA did not predict outcome. Nondiagnostic FNAs of the
      thyroid may be associated with a high probability of thyroid malignancy.
      Nondiagnostic FNAs should not be considered benign. Reaspiration followed by
      selective surgical treatment is recommended.

PMID- 12186503
TI  - Prognostic significance of magnetic resonance findings in advanced papillary
      thyroid cancer.
AB  - We assessed the prognostic importance of magnetic resonance (MR) findings in
      locally advanced papillary thyroid cancer. MR findings, clinical data, and
      pathologic (and surgical) data for 66 patients, including 51 women and 15 men
      with a mean age of 57 years, who had primary surgery for papillary thyroid
      cancers were correlated with prognosis. Mean follow-up was 27.5 months (range, 5
      117 months). Recurrence was seen in 18 patients (27%). In univariate analyses,
      age of 60 years or more (p = 0.0066), male gender (p = 0.0373), six MR findings
      (tumor size of > or = 4 cm ([p = 0.0002], ill-defined margins ([p < 0.0001],
      tumor extension of the trachea [p = 0.0337], carotoid artery [p = 0.0028]),
      esophagus [p < 0.0001], and lymph nodes [p = 0.0005]), and three pathologic
      findings (tumor extension of soft tissues [p = 0.0288], carotid artery [p =
      0.0013], and esophagus [p < 0.0001]) had a significant adverse effect on disease
      free survival. In multivariate analyses, tumor size (p = 0.0169) and nodal
      metastasis (p = 0.0393) determined on MR imaging and pathologic esophageal
      invasion (p = 0.0016) were the only significant independent variables. Esophageal
      invasion was accurately diagnosed with MR imaging (94% accuracy). MR findings may
      contain prognostic importance of locally advanced papillary thyroid cancer.

PMID- 12186504
TI  - The role of radiotherapy in the management of elevated calcitonin after surgery
      for medullary thyroid cancer.
AB  - Among 139 patients with medullary thyroid cancer (MTC) treated at the Royal
      Marsden Hospital between 1957-1998, 51 had persistently elevated calcitonin
      levels after initial surgery in the absence of clinically or radiologically
      demonstrable residual disease. Of these, 24 were treated with radiotherapy
      because of advanced local disease at presentation; this resulted in normalization
      of calcitonin in only 1 patient, although 10 remained free of clinical
      recurrence. Surveillance alone was used in the remaining 27 patients, of whom 8
      (30%) remained free of overt disease. Local relapse rate was significantly lower
      after radiotherapy (29% vs. 59%) but there was no significant difference in 10
      year survival between the two groups (72% vs. 60%). In view of this favorable
      long-term survival of patients with elevated calcitonin on observation, we cannot
      recommend the routine use of radiotherapy. However, it does appear to have a role
      in those presenting with more advanced disease to reduce the incidence of loco
      regional relapse.

PMID- 12186506
TI  - Hypothyroidism and cognition: preliminary evidence for a specific defect in
      memory.
AB  - The effect(s) of hypothyroidism on adult brain cognitive function are poorly
      understood. We performed a series of neuropsychological tests in 13 thyroid
      cancer patients while they continued to take their usual dose of levothyroxine
      (LT4) and again after discontinuing thyroid hormone. Three euthyroid subjects
      were also tested twice to assess the effect of repeated testing on performance.
      The tests assessed memory, mood, and attentional resources and controlled for the
      practice effects of repeated testing. The mean thyrotropin (TSH) on LT4 was 0.56
      +/- 0.76 mU/L and while hypothyroid was 69 +/- 33 mU/L. While hypothyroid, the
      mean Beck depression score was significantly higher (15.31 +/- 9.41 hypothyroid
      vs. 7.31 +/- 4.82 on LT4) and the subjects rated themselves worse relative to
      functional memory, concentration, thinking, alertness, and motivation.
      Hypothyroidism was associated with a decrease in retrieval from memory (p =
      0.0034), and this effect could not be attributed to depression or to practice
      effects. Thyroid state did not affect immediate recall, verbal learning,
      inhibitory efficiency, information processing speed, or attention switching.
      Athyrosis is associated with a decrement in delayed recall of verbal information
      but not in other objective measures of cognition, suggesting that the memory
      decrement of hypothyroidism is not caused by a generalized reduction in
      attentional resources.

PMID- 12186505
TI  - Resistance of [18f]-fluorodeoxyglucose-avid metastatic thyroid cancer lesions to
      treatment with high-dose radioactive iodine.
AB  - Radioactive iodine (131I) is an important therapeutic option for the treatment of
      metastatic thyroid carcinoma. Survival in patients with metastases that
      concentrate radioiodine is better than those whose metastatic lesions do not take
      up radioiodine. Survival is markedly reduced in patients who have metastatic
      lesions that concentrate 18F-fluorodeoxyglucose (FDG) on positron emission
      tomography (PET). In this retrospective study, we evaluated the ability of 131I
      to destroy FDG-avid metastatic lesions in thyroid cancer patients. Twenty-five
      patients with positive FDG-PET scans received at least one dose of 131I treatment
      before a second FDG-PET was performed. The average interval between the two PET
      scans was 12.9 months. The average interval between the 131I treatment and the
      follow-up FDG-PET was 10.1 months. We measured posttherapy changes in lesional
      volume, in standard uptake values (SUV) of FDG, and in serum thyroglobulin (Tg)
      levels. The total volume of FDG-avid metastases rose significantly (p = 0.036)
      from a mean of 159 mL to 235 mL after 131I therapy, the maximum SUV rose from 9.3
      to 11.9, the median Tg at the time of the second PET scan was 132% of that at
      baseline. Statistical analyses demonstrated no significant changes in maximum
      SUV, or serum Tg levels after 131I in the FDG-PET-positive group. In a control
      group of FDG-PET-negative patients, the serum Tg decreased to 38% of baseline
      after 131I therapy (p < 0.001). We conclude that high-dose 131I therapy appears
      to have little or no effect on the viability of metastatic FDG-avid thyroid
      cancer lesions.

PMID- 12186507
TI  - Multifocal fibrosclerosis: a case of thyroiditis and bilateral lacrimal gland
      involvement.
AB  - A patient with invasive fibrous thyroiditis (Riedel's thyroiditis), dysphagia,
      and bilateral lacrimal gland involvement is described. Resolution of the thyroid
      mass and orbital swellings followed corticosteroid therapy. The unusual ocular
      features of this case are briefly discussed and the use of corticosteroid and
      other immunosuppressant therapy in multifocal fibrosclerosis is reviewed.

PMID- 12186508
TI  - Lingual thyroid carcinoma: a case report and review of the literature.
AB  - Ectopic thyroid tissue may reside anywhere along its embryologic path of descent.
      Most ectopias manifest as simple thyroglossal duct cysts in conjunction with a
      normally developed thyroid gland in its usual thyroid cervical bed. Lingual
      thyroid is a rare developmental abnormality characterized by the failure of the
      thyroid gland, or remnants, to descend from its embryologic site of origin at the
      foramen cecum to its usual pretracheal position. Carcinoma arising in a lingual
      thyroid is even more unusual with fewer than 30 cases reported in the literature.
      We report the second case of lingual papillary thyroid carcinoma and review the
      clinical features, natural history, diagnosis, and treatment of lingual thyroid
      carcinoma.

PMID- 12186509
TI  - Thyroid carcinoma in a patient with acromegaly.

PMID- 12186510
TI  - The thyroid gland and beyond.

PMID- 12186511
TI  - Goiter assessment: help or hindrance in tracking progress in iodine deficiency
      disorders control program?

PMID- 12186512
TI  - Economic analysis of influenza vaccination and antiviral treatment for healthy
      working adults.
AB  - BACKGROUND: Physicians have several treatment options for influenza, including
      vaccination and various antiviral therapies. However, the optimal influenza
      prevention and treatment strategy is unknown. OBJECTIVE: To compare the relative
      health values of contemporary treatment strategies for influenza in a healthy
      sample of working adults. DESIGN: Cost-benefit analysis using a decision model.
      DATA SOURCES: Previously published data. TARGET POPULATION: Healthy employed
      adults 18 to 50 years of age. TIME HORIZON: A complete influenza season.
      PERSPECTIVE: Societal. INTERVENTIONS: Eight treatment options (yes or no) based
      on the possible combinations of vaccination and antiviral therapy (rimantadine,
      oseltamivir, or zanamivir or no treatment) should infection develop. OUTCOME
      MEASURES: Cost in U.S. dollars, including the value of symptom relief and
      medication side effects, which was assigned a monetary value through a conjoint
      analysis that used a "willingness-to-pay" approach. RESULTS: In the base-case
      analysis, all strategies for influenza vaccination had a higher net benefit than
      the nonvaccination strategies. Vaccination and use of rimantadine, the most cost
      beneficial strategy, was $30.97 more cost-beneficial than nonvaccination and no
      use of antiviral medication. The health benefits of most antiviral treatments
      equaled or exceeded their costs for most scenarios. The choice of the most cost
      beneficial antiviral strategy was sensitive to the prevalence of influenza B and
      to the comparative workdays gained by each antiviral therapy. CONCLUSIONS:
      Vaccination is cost-beneficial in most influenza seasons in healthy working
      adults. Although the benefits of antiviral therapy for persons with influenza
      infection appear to justify its cost, head-to-head trials of the various
      antiviral therapies are needed to determine the optimal treatment strategy.

PMID- 12186513
TI  - Is duplex ultrasonography useful for the diagnosis of giant-cell arteritis?.
AB  - BACKGROUND: Evidence of a dark halo on ultrasonography has been considered a
      specific sign of giant-cell arteritis and may replace temporal artery biopsy for
      the diagnosis of giant-cell arteritis in patients with typical clinical
      manifestations. OBJECTIVE: To assess the usefulness of temporal artery duplex
      ultrasonography and to compare this mode of ultrasonography with physical
      examination of temporal arteries for the diagnosis of giant-cell arteritis in
      patients with suspected giant-cell arteritis or polymyalgia rheumatica. DESIGN:
      Diagnostic test study. SETTING: Several divisions of Reggio Emilia Hospital,
      Reggio Emilia, Italy. PATIENTS: 86 consecutive patients with a suspected
      diagnosis of giant-cell arteritis or polymyalgia rheumatica identified over a 22
      month period. MEASUREMENTS: The temporal arteries were examined in all 86
      patients. Duplex ultrasonography of the temporal arteries was then performed by
      two ultrasonographers who were unaware of the clinical diagnosis. Before
      corticosteroid therapy was started, temporal artery biopsies were performed in
      all patients at the site targeted by the ultrasonographer. RESULTS: A hypoechoic
      halo around the lumen of the temporal arteries had a sensitivity of only 40% (95%
      CI, 16% to 68%) and a specificity of 79% (CI, 68% to 88%) for the diagnosis of
      biopsy-proven giant-cell arteritis. The negative likelihood ratio was 0.8 (CI,
      0.5 to 1.2), and the positive likelihood ratio was 1.9 (CI, 0.9 to 4.1). When the
      thickness of the halo was at least 1 mm, specificity increased to 93% (CI, 84% to
      98%) and the positive likelihood ratio increased to 5.7 (CI, 2.0 to 16.2);
      however, sensitivity remained low at 40% (CI, 16% to 68%). On physical
      examination, temporal artery abnormalities had a higher sensitivity of 67% (CI,
      38% to 88%), a higher specificity of 99% (CI, 92% to 100%), and a higher positive
      likelihood ratio of 47.3 (CI, 6.5 to 342.4) than did ultrasonographic findings.
      None of the patients with giant-cell arteritis had a normal temporal artery
      inspection and a hypoechoic halo on ultrasonography. CONCLUSION: Evidence on
      ultrasonography of a halo around temporal arteries, either any halo or a halo 1
      mm or greater in thickness, only modestly increased the probability of biopsy
      proven giant-cell arteritis but did not improve the diagnostic accuracy of a
      careful physical examination.

PMID- 12186514
TI  - Safe interruption of maintenance therapy against previous infection with four
      common HIV-associated opportunistic pathogens during potent antiretroviral
      therapy.
AB  - BACKGROUND: The safety of interrupting maintenance therapy for previous
      opportunistic infections other than Pneumocystis carinii pneumonia among patients
      with HIV infection who respond to potent antiretroviral therapy has not been well
      documented. OBJECTIVE: To assess the safety of interrupting maintenance therapy
      for cytomegalovirus (CMV) end-organ disease, disseminated Mycobacterium avium
      complex (MAC) infection, cerebral toxoplasmosis, and extrapulmonary
      cryptococcosis in patients receiving antiretroviral therapy. DESIGN:
      Observational study. SETTING: Seven European HIV cohorts. PATIENTS: 358 patients
      taking potent antiretroviral therapy (> or =3 drugs) who interrupted maintenance
      therapy at a CD4 lymphocyte count greater than 50 x 10(6) cells/L. MEASUREMENTS:
      Recurrence of opportunistic infection after interruption of maintenance therapy.
      RESULTS: 379 interruptions of maintenance therapy were identified: 162 for CMV
      disease, 103 for MAC infection, 75 for toxoplasmosis, and 39 for cryptococcosis.
      During 781 person-years of follow-up, five patients had relapse. Two relapses
      (one of CMV disease and one of MAC infection) were diagnosed after maintenance
      therapy was interrupted when the CD4 lymphocyte count was less than 100 x 10(6)
      cells/L or when only one recent measurement exceeded this value. Two relapses
      (one of CMV disease and one of MAC infection) were diagnosed after maintenance
      therapy was interrupted once CD4 counts were greater than 100 x 10(6) cells/L for
      10 and 8 months, respectively. One relapse (toxoplasmosis) was diagnosed after
      maintenance therapy interruption at a CD4 lymphocyte count greater than 200 x
      10(6) cells/L for 15 months. The overall incidences of recurrent CMV disease, MAC
      infection, toxoplasmosis, and cryptococcosis were 0.54 per 100 person-years (95%
      CI, 0.07 to 1.95 per 100 person-years), 0.90 per 100 person-years (CI, 0.11 to
      3.25 per 100 person-years), 0.84 per 100 person-years (CI, 0.02 to 4.68 per 100
      person-years), and 0.00 per 100 person-years (CI, 0.00 to 5.27 per 100 person
      years), respectively. CONCLUSION: Maintenance therapy against previous infection
      with CMV, MAC, Toxoplasma gondii, or Cryptococcus neoformans in patients with HIV
      infection can be interrupted after sustained CD4 count increases to greater than
      200 (or possibly 100 to 200) x 10(6) cells/L for at least 6 months after the
      start of potent antiretroviral therapy.

PMID- 12186515
TI  - Oral vitamin K lowers the international normalized ratio more rapidly than
      subcutaneous vitamin K in the treatment of warfarin-associated coagulopathy. A
      randomized, controlled trial.
AB  - BACKGROUND: Excessive anticoagulation due to warfarin use is associated with
      hemorrhage. Subcutaneously administered vitamin K has not been evaluated for the
      treatment of warfarin-associated coagulopathy, yet it is widely used. OBJECTIVE:
      To show that oral vitamin K is more effective than subcutaneous vitamin K in the
      treatment of warfarin-associated coagulopathy. DESIGN: Randomized, controlled
      trial. SETTING: Two teaching hospitals. PATIENTS: Patients with an international
      normalized ratio (INR) between 4.5 and 10.0. INTERVENTION: Warfarin therapy was
      withheld, and 1 mg of vitamin K was given orally or subcutaneously. MEASUREMENTS:
      The primary outcome measure was the INR on the day after administration of
      vitamin K. Secondary outcome measures were hemorrhage and thrombosis during a 1
      month follow-up period. RESULTS: 15 of 26 patients receiving oral vitamin K and 6
      of 25 patients receiving subcutaneous vitamin K had therapeutic INRs on the day
      after study drug administration (P = 0.015; odds ratio, 4.32 [95% CI, 1.13 to
      17.44]). CONCLUSION: Oral vitamin K lowers INR more rapidly than subcutaneous
      vitamin K in asymptomatic patients who have supratherapeutic INR values while
      receiving warfarin.

PMID- 12186516
TI  - U.S. Centers for Disease Control and Prevention guidelines for the treatment of
      sexually transmitted diseases: an opportunity to unify clinical and public health
      practice.
AB  - Sexually transmitted diseases (STDs) constitute an epidemic of tremendous
      magnitude, with an estimated 15 million persons in the United States acquiring a
      new STD each year. Effective clinical management of STDs is a strategic common
      element in efforts to prevent HIV infection and to improve reproductive and
      sexual health. Sexually transmitted diseases may result in severe, long-term,
      costly complications, including facilitation of HIV infection, tubal infertility,
      adverse outcomes of pregnancy, and cervical and other types of anogenital cancer.
      The publication of national guidelines for the management of STDs, by the U.S.
      Centers for Disease Control and Prevention (CDC), has been a key component of
      federal initiatives to improve the health of the U.S. population by preventing
      and controlling STDs and their sequelae. This paper presents new recommendations
      from the 2002 CDC Guidelines for the Treatment of Sexually Transmitted Diseases
      in the context of current disease trends and public health.

PMID- 12186517
TI  - Tests of glycemia for the diagnosis of type 2 diabetes mellitus.
AB  - This paper discusses tests of glycemia for the diagnosis of type 2 diabetes
      mellitus, with particular reference to the 1997 diagnostic criteria of the
      American Diabetes Association. The potential benefits of the lower diagnostic
      threshold for fasting plasma glucose are not well defined. However, the change in
      the diagnostic cut-off for diabetes mellitus affects as many as 1.9 million
      persons in the United States; therefore, the medical and social costs of the
      lower threshold may be considerable. Type 2 diabetes mellitus is defined by a
      threshold imposed on the continuous distribution of glycemic levels, typically
      with respect to risk for microvascular complications. However, the burden of type
      2 diabetes relates more to macrovascular than microvascular complications.
      Because no clear threshold exists for macrovascular complications, a formal
      balancing of direct and indirect costs with both microvascular and macrovascular
      complications may be appropriate to establish glycemic thresholds. Because
      fasting plasma glucose, hemoglobin A1c, and the oral glucose tolerance test all
      predict diabetic complications yet test reliability is better for fasting plasma
      glucose and hemoglobin A1c than for the oral glucose tolerance test, we suggest
      an alternative diagnostic approach: If random plasma glucose is elevated (> or
      =11.1 mmol/L [200 mg/dL]) and the hemoglobin A1c level is more than 2 SDs above
      the laboratory mean, then diabetes mellitus should be diagnosed, and management
      should be based on the hemoglobin A1c level. If the result of only one of these
      tests is positive, then fasting plasma glucose should be tested to evaluate the
      patient for impaired fasting glucose and diabetes mellitus. The glycemic
      threshold for type 2 diabetes should be established by cost-effectiveness
      analysis. The clinical diagnosis of diabetes mellitus could be streamlined by
      incorporation of hemoglobin A1c into established criteria.

PMID- 12186518
TI  - Postmenopausal hormone replacement therapy and the primary prevention of
      cardiovascular disease.
AB  - PURPOSE: To evaluate the value of hormone replacement therapy (HRT) in the
      primary prevention of cardiovascular disease (CVD) and coronary artery disease
      (CAD). DATA SOURCES: MEDLINE and Cochrane databases were searched for all primary
      prevention studies reporting CVD or CAD incidence, mortality, or both in
      association with HRT; reference lists, letters, editorials, and reviews were also
      reviewed. DATA EXTRACTION: All studies were reviewed, abstracted, and rated for
      quality. STUDY SELECTION: Only studies of good or fair quality, according to U.S.
      Preventive Services Task Force (USPSTF) criteria, were included in the detailed
      review and meta-analysis. DATA SYNTHESIS: The summary relative risk with any HRT
      use was 0.75 (95% credible interval [CrI], 0.42 to 1.23) for CVD mortality and
      0.74 (CrI, 0.36 to 1.45) for CAD mortality. The summary relative risk with any
      use was 1.28 (CrI, 0.86 to 2.00) for CVD incidence and 0.87 (CrI, 0.62 to 1.21)
      for CAD incidence. Further analysis of studies adjusting for socioeconomic
      status, as well as other major CAD risk factors, showed a summary relative risk
      of 1.07 (CrI, 0.79 to 1.48) for CAD incidence associated with any HRT use.
      Similar results were found when the analysis was stratified by studies adjusting
      for alcohol consumption, exercise, or both, in addition to other major risk
      factors, suggesting confounding by these factors. CONCLUSIONS: This meta-analysis
      differs from previous meta-analyses by evaluating potential explanatory variables
      of the relationship between HRT, CVD, and CAD. The adjusted meta-analysis is
      consistent with recent randomized trials that have shown no benefit in the
      secondary or primary prevention of CVD events. A valid answer to the role of HRT
      in the primary prevention of CVD will best come from randomized, controlled
      trials.

PMID- 12186519
TI  - Discontinuing prophylaxis against recurrent opportunistic infections in HIV
      infected persons: a victory in the era of HAART.

PMID- 12186520
TI  - Articles on diagnostic tests: a new series and an invitation to authors.

PMID- 12186521
TI  - Postmenopausal hormone replacement therapy: how could we have been so wrong?.

PMID- 12186522
TI  - Precious cargo.

PMID- 12186523
TI  - Drop-in.

PMID- 12186524
TI  - Delirium at the end of life.

PMID- 12186526
TI  - Clinical trials testing the homocysteine hypothesis.

PMID- 12186527
TI  - Infliximab therapy for complicated sarcoidosis.

PMID- 12186528
TI  - Infliximab therapy for complicated sarcoidosis.

PMID- 12186530
TI  - Colitis associated with variant Clostridium difficile.

PMID- 12186531
TI  - Effect of angiotensin-converting enzyme inhibitors on progression of nondiabetic
      renal disease.

PMID- 12186533
TI  - Ischemic colitis associated with anti-beta2 glycoprotein-I antibody.

PMID- 12186535
TI  - Chronic HIV infection: can anyone afford a drug holiday?.

PMID- 12186536
TI  - Summaries for patients. Influenza vaccination or antiviral treatment for healthy
      working adults: an economic analysis.

PMID- 12186537
TI  - Summaries for patients. Physical examination or duplex ultrasonography for the
      diagnosis of giant-cell arteritis.

PMID- 12186538
TI  - Summaries for patients. Can maintenance therapy for opportunistic infections in
      HIV-infected people be stopped safely?

PMID- 12186539
TI  - Summaries for patients. Vitamin K reverses overanticoagulation with warfarin more
      quickly when given by mouth than by injection.

PMID- 12186540
TI  - A reexamination of the nucleotide incorporation fidelity of DNA polymerases.
AB  - Intensive study has been devoted to understanding the kinetic and structural
      bases underlying the exceptionally high fidelity (low error frequencies) of the
      typical DNA polymerase. Commonly proposed explanations have included (i) the
      concept of fidelity check points, in which the correctness of a nascent base pair
      match is tested at multiple points along the reaction pathway, and (ii) an
      induced-fit fidelity enhancement mechanism based on a rate-limiting, substrate
      induced conformational change. In this article, we consider the evidence and
      theoretical framework for the involvement of such mechanisms in fidelity
      enhancement. We suggest that a "simplified" model, in which fidelity is derived
      fundamentally from differential substrate binding at the transition state of a
      rate-limiting chemical step, is consistent with known data and sufficient to
      explain the substrate selectivity of these enzymes.

PMID- 12186541
TI  - Mechanistic comparison of the cobalt-substituted and wild-type copper amine
      oxidase from Hansenula polymorpha.
AB  - A recent report by Mills and Klinman [Mills, S. A., and Klinman, J. P. (2000) J.
      Am. Chem. Soc. 122, 9897-9904] described the preparation and initial
      characterization of a cobalt-substituted form of the copper amine oxidase from
      Hansenula polymorpha (HPAO). This enzyme was found to be fully catalytically
      active at saturating substrate concentrations, but with a K(m) for O(2)
      approximately 70-fold higher than that of the copper-containing, wild-type
      enzyme. Herein, we report a detailed analysis of the mechanism of catalysis for
      the wild-type and the cobalt-substituted forms of HPAO. Both forms of enzyme are
      concluded to utilize the same mechanism for oxygen reduction, involving initial,
      rate-limiting electron transfer from the reduced cofactor of the enzyme to
      prebound dioxygen. Superoxide formed in this manner is stabilized by the active
      site metal, facilitating the transfer of a second electron and two protons to
      form the product hydrogen peroxide. The elevated K(m) for O(2) at the dioxygen
      binding site in Co-substituted HPAO, relative to that of wild-type HPAO, is
      proposed to be due to a change in the net charge at the adjacent metal site from
      +1 (cupric hydroxide) in wild-type enzyme to +2 (cobaltous H(2)O) in cobalt
      substituted HPAO.

PMID- 12186542
TI  - The different energetic state of the intra A-chain/domain disulfide of insulin
      and insulin-like growth factor 1 is mainly controlled by their B-chain/domain.
AB  - Insulin and insulin-like growth factor 1 (IGF-1) share homologous sequence,
      similar three-dimensional structure, and weakly overlapping biological activity,
      but different folding information is stored in their homologous sequences: the
      sequence of insulin encodes one unique thermodynamically stable three-dimensional
      structure while that of IGF-1 encodes two disulfide isomers with different three
      dimensional structure but similar thermodynamic stability. Their different
      folding behavior probably resulted from the different energetic state of the
      intra A-chain/domain disulfide: the intra A-chain disulfide of insulin is a
      stable bond while that of IGF-1 is a strained bond with high energy. To find out
      the sequence determinant of the different energetic state of their intra A
      chain/domain disulfide, the following experiments were carried out. First, a
      local chimeric single-chain insulin (PIP) with the A8-A10 residues replaced by
      the corresponding residues of IGF-1 was prepared. Second, the disulfide stability
      of two global hybrids of insulin and IGF-1, Ins(A)/IGF-1(B) and Ins(B)/IGF-1(A),
      was investigated. The local segment swap had no effect on the fidelity of
      disulfide pairing and the disulfide stability of PIP molecule although the
      swapped segment is close to the intra A-chain/domain disulfide. In redox buffer
      which favors the disulfide formation for most proteins, Ins(A)/IGF-1(B) cannot
      form and maintain its native disulfides just like that of IGF-1, while the
      disulfides of Ins(B)/IGF-1(A) are stable in the same condition. One major
      equilibrium intermediate with two disulfides of Ins(A)/IGF-1(B) was purified and
      characterized. V8 endoproteinase cleavage and circular dichroism analysis
      suggested that the intra A-chain/domain disulfide was reduced in the
      intermediate. Our present results suggested that the energetic state of the intra
      A-chain/domain disulfide of insulin and IGF-1 was not controlled by the A
      chain/domain sequence close to this disulfide but was mainly controlled by the
      sequence of the B-chain/domain.

PMID- 12186543
TI  - Monounsaturated PE does not phase-separate from the lipid raft molecules
      sphingomyelin and cholesterol: role for polyunsaturation?
AB  - We investigated interactions of the lipid raft molecules sphingomyelin (SM) and
      cholesterol (CHOL) in monolayers and bilayers composed of 1-palmitoyl-2-oleoyl-sn
      glycerophosphatidylethanolamine (POPE) or 1-palmitoyl-2-docosahexaenoyl-sn
      glycerophosphatidylethanolamine (PDPE) at 35 degrees C. Techniques employed were
      pressure-area (pi-A) isotherms generated from Langmuir-Blodgett films, solid
      state (2)H and (31)P NMR spectroscopies, and differential scanning calorimetry
      (DSC). Condensation calculated from pi-A isotherms and reduction in the enthalpy
      of the gel-liquid-crystalline transition in DSC scans showed CHOL has a strong
      affinity for POPE, comparable to that observed between SM-CHOL. Order parameters
      derived from (2)H NMR spectra of the perdeuterated sn-1 chain of POPE-d(31)
      increased by >50% upon addition of equimolar CHOL to POPE-d(31)/SM (1:1 mol)
      bilayers. Close proximity of CHOL to POPE even in the presence of SM is
      indicated. Chemical shift anisotropy (Deltasigma(csa)) measured from (1)H
      decoupled (31)P NMR spectra also implied intimate lipid mixing in POPE/SM/CHOL
      (1:1:1 mol). In contrast, pi-A isotherms and corroborating DSC studies of PDPE/SM
      (1:1 mol) indicate phase separation between SM and PDPE, which was maintained in
      the presence of CHOL. The cholesterol-associated increase in order of the
      perdeuterated sn-1 chain of PDPE determined by (2)H NMR was 2-fold less for PDPE
      d(31)/SM/CHOL (1:1:1 mol) than POPE-d(31)/SM/CHOL (1:1:1 mol). Our findings
      support the notion that acyl chain dependent lateral phase separation occurs in
      the presence of a docosahexaenoic acid (DHA)-containing phospholipid (PDPE), but
      not an oleic acid-containing phospholipid (POPE). We propose that monounsaturated
      lipids do not promote formation of stable lipid rafts and that polyunsaturation
      may be important for raft stability.

PMID- 12186544
TI  - In vitro evolution of amphioxus insulin-like peptide to mammalian insulin.
AB  - By site-directed mutagenesis, six insulin residues related to the insulin
      receptor interaction were grafted, partially or fully, onto the corresponding
      position of a recombinant amphioxus insulin-like peptide (ILP) that contained the
      A- and B-domains of the deduced amphioxus ILP. After fermentation, purification,
      and enzymatic cleavage, six insulin-like double-chain ILP analogues were
      obtained: [A2Ile]ILP, [B12Val, B16Tyr]ILP, [B25Phe]ILP, [A2Ile, B12Val, B16Tyr,
      B25Phe]ILP (four-mutated ILP), [A2Ile, B12Val, B16Tyr, B24Phe, B25Phe]ILP (five
      mutated ILP), and [A2Ile, B12Val, B16Tyr, B24Phe, B25Phe, B26Tyr]ILP (six-mutated
      ILP). Circular dichroism analysis showed that such replacement did not
      significantly affect their secondary and tertiary structure compared with that of
      the wild-type ILP. The insulin-receptor-binding activity of the four-, five-, and
      six-mutated ILP was 0.14%, 11%, and 11% of native insulin, respectively; the
      other three ILP analogues acquired none of the detectable insulin-receptor
      binding potency. The growth-promoting activities of the five- and six-mutated ILP
      were both about 50% of native insulin, while that of the wild-type ILP was not
      detectable. By structure-function-based mutagenesis, the completely inactive
      amphioxus ILP was converted into a molecule with moderate mammalian insulin
      activity. These results indicated the following: first, the grafted as well as
      those inborn insulin-receptor-binding related residues can form an insulin
      receptor-binding patch on the ILP analogues; second, the ILP can be used as a
      scaffold molecule to investigate the role of the insulin residues; third, the
      natural evolution of amphioxus ILP to mammalian insulin is a possible process and
      can be mimicked in the laboratory.

PMID- 12186545
TI  - A conserved cis peptide bond is necessary for the activity of Bowman-Birk
      inhibitor protein.
AB  - The Bowman-Birk inhibitor (BBI) family of protease inhibitors has an inhibitory
      region comprising a disulfide-linked nine-residue loop that adopts the
      characteristic canonical motif found in many serine protease inhibitors. A unique
      feature of the BBI loop is the presence of a cis peptide bond at the edge of the
      inhibitory loop. BBI-related protein fragments that encapsulate this loop retain
      the structure and inhibitory activity of the parent protein. The most common BBI
      loop sequence has a proline-proline element with a cis-trans geometry at P3'-P4'.
      We have examined this element by analysis of the inhibitory activity and
      structure for a series of synthetic fragments where each of these proline
      residues has been systematically replaced with alanine. The results show that
      only when a proline is present at P3' are potent inhibition and a cis peptide
      bond at that position in the solution structure observed, suggesting that this
      conformation is required for biological activity. Though a P4' proline is not
      essential for activity, it effectively stabilizes the cis conformation at P3' by
      suppressing alternative conformations. This is most evident from the Pro-Ala
      variant, which comprises a 1:1 mixture of slowly exchanging and structurally
      different cis and trans isomers. Monitoring the action of trypsin on this mixture
      by NMR shows that this protease interacts selectively with the cis P3' structure,
      providing direct evidence for the link between activity and the nativelike
      structure of the cis isomer. This is, to the best of our knowledge, the first
      example where cis isomer selectivity can be demonstrated for a proteinase.

PMID- 12186546
TI  - Inhibition of superoxide generation from neuronal nitric oxide synthase by heat
      shock protein 90: implications in NOS regulation.
AB  - Besides NO, neuronal NO synthase (nNOS) also produces superoxide (O(2)(-.) at low
      levels of L-arginine. Recently, heat shock protein 90 (hsp90) was shown to
      facilitate NO synthesis from eNOS and nNOS. However, the effect of hsp90 on the
      O(2)(-.) generation from NOS has not been determined yet. The interrelationship
      between its effects on O(2)(-.) and NO generation from NOS is also unclear.
      Therefore, we performed electron paramagnetic resonance measurements of O(2)(-.)
      generation from nNOS to study the effect of hsp90. Purified rat nNOS generated
      strong O(2)(-.) signals in the absence of L-arginine. In contrast to its effect
      on NO synthesis, hsp90 dose-dependently inhibited O(2)(-.) generation from nNOS
      with an IC(50) of 658 nM. This inhibition was not due to O(2)(-.) scavenging
      because hsp90 did not affect the O(2)(-.) generated by xanthine oxidase. At lower
      levels of L-arginine where marked O(2)(-.) generation occurred, hsp90 caused a
      more dramatic enhancement of NO synthesis from nNOS as compared to that under
      normal L-arginine. Significant O(2)(-.) production was detected from nNOS even at
      intracellular levels of L-arginine. Adding hsp90 prevented this O(2)(-.)
      production, leading to enhanced nNOS activity. Thus, these results demonstrated
      that hsp90 directly inhibited O(2)(-.) generation from nNOS. Inhibition of O(2)(
      .) generation may be an important mechanism by which hsp90 enhances NO synthesis
      from NOS.

PMID- 12186547
TI  - Discrimination of tRNA(Leu) isoacceptors by the mutants of Escherichia coli
      leucyl-tRNA synthetase in editing.
AB  - Leucyl-tRNA synthetase (LeuRS), one of the class Ia aminoacyl-tRNA synthetases,
      joins Leu to tRNA(Leu) and excludes noncognate amino acids in protein synthesis.
      In this study, Escherichia coli LeuRS mutants at amino acid E292, which was
      located in the connective polypeptide 1 insertion region, were synthesized.
      Although mutated LeuRS showed little change in structure compared with wild-type
      LeuRS, the mutants were impaired in activity to varying extents. It was also
      showed that mutations did not affect the adenylation reaction. However, mutated
      LeuRS can mischarge tRNA(Leu) isoacceptors tRN or tRN with isoleucine to
      different extents. Isoleucylation of tRN was more than that of tRN. The mutant
      LeuRS-E292S, which was picked out as an example for the investigation of the
      relationship between tRNA(Leu) isoacceptors and editing function, can
      discriminate the Watson-Crick base pair of the first base pair of tRNA(Leu) from
      the wobble base pair. The tRNA(Leu) with the Watson-Crick base pair may result in
      more isoleucylated product than that with the wobble base pair. The same
      phenomenon happened to another mutant, LeuRS-A293D. It seems that the flexibility
      of the first base pair affects the editing reaction of LeuRS. The results
      indicate that the flexibility of the first base pair of tRNA(Leu) may probably
      affect the mischarged 3'-end of tRNA(Leu) shuttling from synthetic site to
      editing site and that the transferred acceptor arm of tRNA(Leu) may interact with
      LeuRS in the region around E292.

PMID- 12186548
TI  - Specificity of the interaction between the Paracoccus denitrificans oxidase and
      its substrate cytochrome c: comparing the mitochondrial to the homologous
      bacterial cytochrome c(552), and its truncated and site-directed mutants.
AB  - Under in vitro conditions, bacterial cytochrome c oxidases may accept several
      nonhomologous c-type electron donors, including the evolutionarily related
      mitochondrial cytochrome c. Several lines of evidence suggest that in intact
      membranes the heme aa(3) oxidase from Paracoccus denitrificans receives its
      electrons from the membrane-bound cytochrome c(552). Both the structures of the
      oxidase and of a heterologously expressed, soluble fragment of the c(552) have
      been determined recently, but no direct structural information about a static
      cocomplex is available. Here, we analyze the kinetic properties of the isolated
      oxidase with the full-size c(552), with two truncated soluble forms, and with a
      set of site-specific mutants within the presumed docking site of the cytochrome,
      all heterologously expressed in Escherichia coli. Our data indicate that all
      three forms, the wild type and both truncations, are fully competent kinetically
      and exhibit biphasic kinetic behavior, however, under widely different ionic
      strength conditions. When mutations in lysine residues clustered around the
      interaction domain were introduced into the smallest fragment of c(552), both
      kinetic parameters, K(M) and k(cat), were drastically influenced. On the other
      hand, when the nonmutated truncated form was used to donate electrons to a set of
      oxidase mutants with replacements clustered along the docking site on subunit II,
      we observe distinct differences when comparing the kinetic properties of the
      widely used horse heart cytochrome c with those of the bacterial c(552). We
      conclude that the specific docking sites for the two types of cytochromes differ
      to some extent.

PMID- 12186549
TI  - Attenuation of the editing activity of the Escherichia coli leucyl-tRNA
      synthetase allows incorporation of novel amino acids into proteins in vivo.
AB  - The fidelity of translation is dependent on the specificity of the aminoacyl-tRNA
      synthetases (aaRSs). The aaRSs that activate the hydrophobic amino acids leucine,
      isoleucine, and valine employ a proofreading mechanism that hydrolyzes noncognate
      aminoacyl adenylates and misaminoacylated tRNAs. Discrimination between
      structurally similar amino acids by these AARSs is believed to operate by a
      double-sieve principle, wherein a separate editing domain governs hydrolysis on
      the basis of the size and hydrophilicity of the amino acid side chain. Leucyl
      tRNA synthetase (LeuRS) relies on its editing function to correct
      misaminoacylation of tRNA(Leu) by isoleucine and methionine. Thr252 of
      Escherichia coli LeuRS has been shown previously to be important in defining the
      size of the editing cavity. Here we report the isolation and characterization of
      three LeuRS mutants with point mutations at this position (T252Y, T252L, and
      T252F). The proofreading activity of the synthetase is significantly impaired
      when an amino acid bulkier than threonine is introduced. The rate of
      misaminoacylation of tRNA(Leu) by isoleucine and valine increases with the
      increasing size of the amino acid substituent at position 252, and the noncognate
      amino acids norvaline and norleucine are inserted efficiently at the leucine
      sites of recombinant proteins under conditions of constitutive overexpression of
      the T252Y mutant in E. coli. In addition, the unsaturated amino acids
      allylglycine, homoallylglycine, homopropargylglycine, and 2-butynylalanine all
      support protein synthesis in E. coli hosts harboring the mutant synthetase. These
      results demonstrate that programmed manipulation of the editing cavity can allow
      in vivo incorporation of novel protein building blocks.

PMID- 12186550
TI  - Formation of a copper specific binding site in non-native states of beta-2
      microglobulin.
AB  - A debilitating complication of long-term hemodialysis is the deposition of beta-2
      microglobulin (beta2m) as amyloid plaques in the joint space. We have recently
      shown that Cu(2+) can be a contributing, if not causal, factor at concentrations
      encountered during dialysis therapy. The basis for this effect is destabilization
      and incorporation of beta2m into amyloid fibers upon binding of Cu(2+). In this
      work, we demonstrate that while beta2m binds Cu(2+) specifically in the native
      state, it is binding of Cu(2+) by non-native states of beta2m which is
      responsible for destabilization. Mutagenesis of potential coordinating groups for
      Cu(2+) shows that native state binding of Cu(2+) is mediated by residues and
      structures that are different than those which bind in non-native states. An
      increased affinity for copper by non-native states compared to that of the native
      state gives rise to overall destabilization. Using mass spectrometry, NMR, and
      fluorescence techniques, we show that native state binding is localized to H31
      and W60 and is highly specific for Cu(2+) over Zn(2+) and Ni(2+). Binding of
      Cu(2+) in non-native states of beta2m is mediated by residues H13, H51, and H84,
      but not H31. Although denatured beta2m has characteristics of a globally unfolded
      state, it nevertheless demonstrates the following strong specificity of binding:
      Cu(2+) > Zn(2+) >> Ni(2+). This requires the existence of a well-defined
      structure in the unfolded state of this protein. As Cu(2+) effects are reported
      in many other amyloidoses, e.g., PrP, alpha-synuclein, and Abeta, our results may
      be extended to the emerging field of divalent ion-associated amyloidosis.

PMID- 12186551
TI  - Solution structure of ascidian trypsin inhibitor determined by nuclear magnetic
      resonance spectroscopy.
AB  - The three-dimensional solution structure of ascidian trypsin inhibitor (ATI), a
      55 amino acid residue protein with four disulfide bridges, was determined by
      means of two-dimensional nuclear magnetic resonance (2D NMR) spectroscopy. The
      resulting structure of ATI was characterized by an alpha-helical conformation in
      residues 35-42 and a three-stranded antiparallel beta-sheet in residues 22-26, 29
      32, and 48-50. The presence of an alpha-helical conformation was predicted from
      the consensus sequences of the cystine-stabilized alpha-helical (CSH) motif,
      which is characterized by an alpha-helix structure in the Cys-X(1)-X(2)-X(3)-Cys
      portion (corresponding to residues 37-41), linking to the Cys-X-Cys portion
      (corresponding to residues 12-14) folded in an extended structure. The secondary
      structure and the overall folding of the main chain of ATI were very similar to
      those of the Kazal-type inhibitors, such as Japanese quail ovomucoid third domain
      (OMJPQ3) and leech-derived tryptase inhibitor form C (LDTI-C), although ATI does
      not show extensive sequence homology to these inhibitors except for a few amino
      acid residues and six of eight half-cystines. On the basis of these findings, we
      realign the amino acid sequences of representative Kazal-type inhibitors
      including ATI and discuss the unique structure of ATI with four disulfide
      bridges.

PMID- 12186552
TI  - Thermodynamic analysis of conserved loop-stem interactions in P1-P2 frameshifting
      RNA pseudoknots from plant Luteoviridae.
AB  - The RNA genomes of plant luteovirids beet western yellows virus (BWYV), potato
      leaf roll virus (PLRV), and pea enation mosaic virus (PEMV RNA1; PEMV-1) contain
      a short mRNA pseudoknotted motif overlapping the P1 and P2 open reading frames
      required for programmed -1 mRNA ribosomal frameshifting. The relationship between
      structure, stability, and function is poorly understood in these RNA systems. A
      m(5)-C(8)-substituted BWYV RNA is employed to establish that the BWYV P1-P2
      pseudoknot is protonated at cytidine 8 in loop L1 (delta(N(3)H)+ = 12.98 ppm),
      which stabilizes a C(+.)(G-C) major groove base triple by
      Delta(DeltaG(37))(protonation) = 3.1 (+/-0.4) kcal mol(-1). The stabilities of
      both the PLRV and PEMV-1 P1-P2 pseudoknots are also strongly pH-dependent, with
      Delta(DeltaG(37))(protonation) = 2.1 (+/-0.2) kcal mol(-1) for the PEMV-1
      pseudoknot despite a distinct structural context. As previously found for the
      BWYV pseudoknot [Nixon and Giedroc (2000) J. Mol. Biol. 296, 659], both the PLRV
      and PEMV-1 RNAs are stabilized by DeltaH > or = 30 kcal mol(-)(1) in excess of
      secondary structure predictions, attributed to loop L2-stem S1 minor groove
      triplex interactions. BWYV RNAs containing single 2'-deoxy or A --> G
      substitutions that disrupt L2-S1 hydrogen bonding are strongly destabilized with
      Delta(DeltaG(37))(folding) (pH = 7.0) ranging from approximately 1.8 (+/-0.3) to
      > or =4.0 kcal mol(-1), relative to the wild-type BWYV RNA. These findings
      suggest that each member of this family of pseudoknots adopts a tightly folded
      structure that maximizes the cooperativity and complementarity of L1-S2 and L2-S1
      loop-stem interactions required in part to offset the low intrinsic stability of
      the short three base pair pseudoknot stem S2.

PMID- 12186553
TI  - Identification of the residues involved in stabilization of the semiquinone
      radical in the high-affinity ubiquinone binding site in cytochrome bo(3) from
      Escherichia coli by site-directed mutagenesis and EPR spectroscopy.
AB  - During turnover of cytochrome bo(3) from Escherichia coli, a semiquinone radical
      is stabilized in a high-affinity binding site. To identify binding partners of
      this radical, site-directed mutants have been designed on the basis of a recently
      modeled quinone binding site (Abramson et al., 2000). The R71H, H98F, D75H, and
      I102W mutant enzymes were found to show very little or no quinol oxidase
      activity. The thermodynamic and EPR spectroscopic properties of semiquinone
      radicals in these mutants were characterized. For the H98F and the R71H mutants,
      no EPR signal of the semiquinone radical was observed in the redox potential
      range from -100 to 250 mV. During potentiometric titration of the D75H mutant
      enzyme, a semiquinone signal was detected in the same potential range as that of
      the wild-type enzyme. However, the EPR spectrum of the D75H mutant lacks the
      characteristic hyperfine structure of the semiquinone radical signal observed in
      the wild-type oxidase, indicating that D75 or the introduced His, interacts with
      the semiquinone radical. For the I102W mutant, a free radical signal was observed
      with a redox midpoint potential downshifted by about 200 mV. On the basis of
      these observations, it is suggested that R71, D75, and H98 residues are involved
      in the stabilization of the semiquinone state in the high-affinity binding site.
      Details of the possible binding motif and mechanistic implications are discussed.

PMID- 12186554
TI  - Biochemical, Mossbauer, and EPR studies of the diiron cluster of phenol
      hydroxylase from Pseudomonas sp. strain CF 600.
AB  - Phenol hydroxylase of Pseudomonas sp. strain CF600 comprises three components:
      DmpP is an FAD- and [2Fe-2S]-containing reductase; DmpM is a cofactorless
      activator protein; and DmpLNO is the oxygenase. Single turnover experiments
      established that DmpLNO contains the active site, but requires DmpM for efficient
      turnover: the steady-state turnover rate reaches a maximum at 1.5 DmpM:1 DmpLNO.
      Chemical cross-linking experiments showed that DmpM interacts with the large
      subunit of the DmpLNO oxygenase complex. Mossbauer studies revealed that the
      active site of the oxygenase can accommodate two types of diiron clusters, each
      of these cluster types having two equivalent sites. Cluster form I, representing
      typically around 85% of total Fe, has DeltaE(Q) = 1.73 mm/s and delta = 0.54
      mm/s, while cluster II exhibits DeltaE(Q) = 0.79 mm/s and delta = 0.48 mm/s.
      Studies in strong applied magnetic fields suggest that the two iron sites of
      cluster I are bridged by an oxo group while sites in cluster II appear to be
      hydroxo-bridged. Reduction of the samples with dithionite yields the diferrous
      forms of the clusters. Air oxidation of the reduced samples leads to an increase
      of the cluster II fraction, accompanied by a corresponding decrease in catalytic
      activity. The reduced oxygenase samples exhibit at X-band an integer spin EPR
      signal centered, in parallel mode, at g = 16.6. Quantitative analysis showed that
      19% of the clusters contribute to the EPR signal, suggesting that cluster II is
      the EPR-active species. Incubation with dithiothreitol (DTT) inactivated the
      oxygenase by a mechanism apparently involving H(2)O(2) generation. In addition,
      Mossbauer studies of DTT-inactivated enzyme showed that all ferric iron belonged
      to one diamagnetic diferric cluster with parameters that indicate that DTT
      coordinates to the cluster.

PMID- 12186555
TI  - Phosphorylation of beta-arrestin2 regulates its function in internalization of
      beta(2)-adrenergic receptors.
AB  - Beta-arrestins mediate agonist-dependent desensitization and internalization of G
      protein-coupled receptors. Previously, we have shown that phosphorylation of beta
      arrestin1 by ERKs at Ser-412 regulates its association with clathrin and its
      function in promoting clathrin-mediated internalization of the receptor. In this
      paper we report that beta-arrestin2 is also phosphorylated, predominantly at
      residues Thr-383 and Ser-361. Isoproterenol stimulation of the beta(2)-adrenergic
      receptor promotes dephosphorylation of beta-arrestin2. Mutation of beta-arrestin2
      phosphorylation sites to aspartic acid decreases the association of beta
      arrestin2 with clathrin, thereby reducing its ability to promote internalization
      of the beta(2)-adrenergic receptor. Its ability to bind and desensitize the
      beta(2)-adrenergic receptor is, however, unaltered. These results suggest that,
      analogous to beta-arrestin1, phosphorylation/dephosphorylation of beta-arrestin2
      regulates clathrin-mediated internalization of the beta(2)-adrenergic receptor.
      In contrast to beta-arrestin1, which is phosphorylated by ERK1 and ERK2,
      phosphorylation of beta-arrestin2 at Thr-383 is shown to be mediated by casein
      kinase II. Recently, it has been reported that phosphorylation of visual arrestin
      at Ser-366 prevents its binding to clathrin. Thus it appears that the function of
      all arrestin family members in mediating internalization of G protein-coupled
      receptors is regulated by distinct phosphorylation/dephosphorylation mechanisms.

PMID- 12186557
TI  - Participation of Rac GTPase activating proteins in the deactivation of the
      phagocytic NADPH oxidase.
AB  - The aim of the present study was to investigate possible mechanisms that could be
      involved in the deactivation of the assembled, catalytically active NADPH oxidase
      of phagocytic cells and thereby lead to termination of O(2)(.-) production. Our
      major findings are the following: (1) Addition of GDP to the active oxidase is
      able to reduce O(2)(.-) production both in the fully purified and in a semi
      recombinant cell-free activation system. (2) p67(phox) inhibits GTP hydrolysis on
      Rac whereas p47(phox) has no effect on Rac GTPase activity. (3) Soluble
      regulatory proteins (GTPase activating protein, guanine nucleotide dissociation
      inhibitor, and the Rac-binding domain of the target protein p21-activated kinase)
      inhibit activation of the NADPH oxidase but have no effect on electron transfer
      via the assembled enzyme complex. (4) Membrane-associated GTPase activating
      proteins (GAPs) have access also to the assembled, catalytically active oxidase.
      Taken together, we propose that the GTP-bound active form of Rac is required for
      sustained enzyme activity and that membrane-localized GAPs have a role in the
      deactivation of NADPH oxidase.

PMID- 12186556
TI  - Peptidyl aldehydes as reversible covalent inhibitors of protein tyrosine
      phosphatases.
AB  - Protein tyrosine phosphatases (PTPs) are a large family of enzymes that catalyze
      the hydrolytic removal of the phosphoryl group from phosphotyrosyl (pY) proteins.
      PTP inhibitors provide potential treatment of human diseases/conditions such as
      diabetes and obesity as well as useful tools for studying the function of PTPs in
      signaling pathways. In this work, we have shown that certain aryl-substituted
      aldehydes act as reversible, slow-binding inhibitors of modest potency against
      PTP1B, SHP-1, and a dual-specificity phosphatase, VHR. Attachment of the
      tripeptide Gly-Glu-Glu to the para position of cinnamaldehyde resulted in an
      inhibitor (Cinn-GEE) of substantially increased potency against all three enzymes
      (e.g., K(I) = 5.4 microM against PTP1B). The mechanism of inhibition was
      investigated using Cinn-GEE specifically labeled with (13)C at the aldehyde
      carbon and (1)H-(13)C heteronuclear single-quantum coherence spectroscopy. While
      Cinn-GEE alone showed a single cross-peak at delta 9.64 ((1)H) and delta 201
      ((13)C), the PTP1B/Cinn-GEE complex showed three distinct cross-peaks at delta
      7.6-7.8 ((1)H) and 130-137 ((13)C). Mutation of the catalytic cysteine (Cys-215
      in PTP1B) into alanine had no effect on the cross-peaks, whereas mutation of a
      conserved active-site arginine (Arg-221 in PTP1B) to alanine abolished all three
      cross-peaks. Similar experiments with Cinn-GEE that had been labeled with (13)C
      at the benzylic position revealed a change in the hybridization state (from sp(2)
      to sp(3)) for the benzylic carbon as a result of binding to PTP1B. These results
      rule out the possibility of a free aldehyde, aldehyde hydrate, or hemithioacetal
      as the enzyme-bound inhibitor form. Instead, the data are consistent with the
      formation of an enamine between the aldehyde group of the inhibitor and the
      guanidine group of Arg-221 in the PTP1B active site. These aldehydes may provide
      a general core structure that can be further developed into highly potent and
      specific PTP inhibitors.

PMID- 12186558
TI  - Characterization of linoleic acid nitration in human blood plasma by mass
      spectrometry.
AB  - Nitric oxide (*NO) is a pervasive free radical species that concentrates in
      lipophilic compartments to serve as a potent inhibitor of lipid and low-density
      lipoprotein oxidation processes. In this study, we synthesized, characterized,
      and detected nitrated derivatives of linoleic acid (18:2) in human blood plasma
      using high-pressure liquid chromatography coupled with electrospray ionization
      tandem mass spectrometry. While the reaction of nitronium tetrafluoroborate with
      18:2 presented ions with a mass/charge (m/z) ratio of 324 in the negative ion
      mode, characteristic of nitrolinoleate (LNO(2)), the reaction of nitrite (NO(2)(
      )) with linoleic acid hydroperoxide yielded nitrohydroxylinoleate (LNO(2)OH, m/z
      340). Further analysis by MS/MS gave a major fragment at m/z 46, characteristic
      of a nitro group (-NO(2)) present in the parent ion. This was confirmed by using
      [(15)N]O(2), which gave products of m/z 325 and 341, that after fragmentation
      yielded a daughter ion at m/z 47. Moreover, a C-NO(2) structure was also
      demonstrated in LNO(2)OH by nuclear magnetic resonance spectroscopy ((15)N NMR,
      delta 375.9), as well as by infrared analysis in both LNO(2)OH (nu(max) = 3427,
      1553, and 1374 cm(-1)) and LNO(2) (nu(max) = 1552 and 1373 cm(-1)). Stable
      products with m/z of 324 and 340, which possessed the same chromatographic
      characteristics and fragmentation pattern as synthesized standards, were found in
      human plasma of normolipidemic and hyperlipidemic donors. The presence of these
      novel nitrogen-containing oxidized lipid adducts in human plasma could represent
      "footprints" of the antioxidant action of *NO on lipid oxidation and/or a pro
      oxidant and nitrating action of *NO-derived species.

PMID- 12186559
TI  - Position-dependent hydrophobicity of the antimicrobial magainin peptide affects
      the mode of peptide-lipid interactions and selective toxicity.
AB  - Cationic antimicrobial peptides are promising candidates as novel antibiotics of
      clinical usefulness. Magainin 2, a representative antimicrobial peptide isolated
      from the skin of the African clawed frog Xenopus leavis, electrostatically
      recognizes anionic lipids that are abundant in bacterial membranes, forming a
      peptide-lipid supramolecular complex pore, whereas the peptide does not
      effectively bind to zwitterionic phospholipids constituting the outer leaflets of
      mammalian cell membranes because of the low hydrophobicity of the peptide
      [Matsuzaki, K. (1999) Biochim. Biophys. Acta 1462, 1-10]. In this study, two
      magainin analogues with enhanced hydrophobicity, MG-H1 (GIKKFLHIIWKFIKAFVGEIMNS)
      and MG-H2 (IIKKFLHSIWKFGKAFVGEIMNI), with identical amino acid compositions were
      designed and interactions with lipid bilayers and biological activities were
      examined in comparison with those of MG (GIGKWLHSAKKFGKAFVGEIMNS = F5W-magainin
      2). The apparent hydrophobicities and hydrophobic moments of MG-H1 and MG-H2,
      conventionally calculated assuming that all residues are involved in helix
      formation, were almost the same. MG-H2 behaved like MG except for greatly
      enhanced activity against zwitterionic membranes and erythrocytes. In contrast,
      despite a very similar calculated hydrophobicity, the observed hydrophobicity of
      MG-H1 was larger than that of MG-H2 because of a tendency toward helix fraying
      near the termini. Therefore, the physicochemical parameters of only the helical
      portion should be considered in characterizing peptide-lipid interactions,
      although this point was overlooked in most studies. Moreover, MG-H1 induced
      aggregation and/or fusion of negatively charged membranes. Furthermore, the
      peptide hydrophobicity was found to affect pore formation rate, pore size, and
      pore stability. These observations demonstrate that the hydrophobicity of the
      peptide also controls the mode of action and is dependent on the position of the
      hydrophobic amino acids in the peptide sequence.

PMID- 12186561
TI  - Archaeological chemistry.

PMID- 12186560
TI  - Phosphorylation of the linker for activation of T-cells by Itk promotes
      recruitment of Vav.
AB  - The linker for activation of T-cells (LAT) is a palmitoylated integral membrane
      adaptor protein that resides in lipid membrane rafts and contains nine consensus
      putative tyrosine phosphorylation sites, several of which have been shown to
      serve as SH2 binding sites. Upon T-cell antigen receptor (TCR/CD3) engagement,
      LAT is phosphorylated by protein tyrosine kinases (PTK) and binds to the adaptors
      Gads and Grb2, as well as to phospholipase Cgamma1 (PLCgamma1), thereby
      facilitating the recruitment of key signal transduction components to drive T
      cell activation. The LAT tyrosine residues Y(132), Y(171), Y(191), and Y(226)
      have been shown previously to be critical for binding to Gads, Grb2, and
      PLCgamma1. In this report, we show by generation of LAT truncation mutants that
      the Syk-family kinase ZAP-70 and the Tec-family kinase Itk favor phosphorylation
      of carboxy-terminal tyrosines in LAT. By direct binding studies using purified
      recombinant proteins or phosphopeptides and by mutagenesis of individual
      tyrosines in LAT to phenylalanine residues, we demonstrate that Y(171) and
      potentially Y(226) are docking sites for the Vav guanine nucleotide exchange
      factor. Further, overexpression of a kinase-deficient mutant of Itk in T-cells
      reduced both the tyrosine phosphorylation of endogenous LAT and the recruitment
      of Vav to LAT complexes. These data indicate that kinases from distinct PTK
      families are likely responsible for LAT phosphorylation following T-cell
      activation and that Itk kinase activity promotes recruitment of Vav to LAT.

PMID- 12186562
TI  - The beginnings of vitreous materials in the Near East and Egypt.
AB  - In the Near East and Egypt, vitreous materials in the form of glazed stones and
      faience were first produced from about the 4th millennium B.C. Subsequently, the
      period around 1500 BC saw major developments in the range of vitreous materials
      with the production of glass vessels and glazed clay objects and an extension in
      the range of colorants used. This paper first describes how the examination of
      artifacts has been used to reconstruct the processes involved in the production
      of these different vitreous materials. This information is then used to try to
      understand how the new technologies were discovered and why they were adopted.

PMID- 12186563
TI  - Tradition and experiment in first millennium a.d. glass production--the emergence
      of early Islamic glass technology in late antiquity.
AB  - Following a brief history of analytical research into ancient glasses, the
      emergence of early Islamic glasses in the Middle East in late antiquity is
      discussed. Data sets for Roman and Byzantine glasses are compared to those of the
      early Islamic period. This is a rare period of technological transition when
      responses to the "drying up" of the traditional mineral alkali source resulted in
      experimentation, which can be demonstrated analytically.

PMID- 12186564
TI  - Instrumental neutron activation analysis of archaeological ceramics: scale and
      interpretation.
AB  - Instrumental neutron activation analysis has become a standard technique for the
      study of the production and distributional patterns of archaeological pottery.
      Questions once framed within the context of long distance exchange are now
      focused on issues of subregional and even intrasite levels. The increasing
      specificity at which these questions are poised requires a high level of
      analytical precision as we seek to observe statistically and archaeologically
      significant differences among groups of pottery produced from geographically
      closely spaced resources or the compositional differences that arise from
      production behaviors of the producers of the pottery.

PMID- 12186565
TI  - Obsidian provenance research in the Americas.
AB  - The characterization of archaeological materials to support provenance research
      has grown rapidly over the past few decades. Volcanic obsidian has several unique
      properties that make it the ideal archaeological material for studying
      prehistoric trade and exchange. This Account describes our laboratory's
      development of a systematic methodology for the characterization of obsidian
      sources and artifacts from Mesoamerica and other regions of North and South
      America in support of archaeological research.

PMID- 12186566
TI  - Chemical fingerprinting and source tracing of obsidian: the central Mediterranean
      trade in black gold.
AB  - Chemical fingerprinting using major or trace element composition is used to
      characterize the Mediterranean island sources of obsidian and can even
      differentiate as many as nine flows in the Monte Arci region of Sardinia.
      Analysis of significant numbers of obsidian artifacts from Neolithic sites in the
      central Mediterranean reveals specific patterns of source exploitation and
      suggests particular trade mechanisms and routes. The use of techniques such as X
      ray fluorescence, the electron microprobe, neutron activation analysis, and laser
      ablation ICP mass spectrometry are emphasized in order to produce quantitative
      results while minimizing damage to valuable artifacts.

PMID- 12186567
TI  - Amber: the organic gemstone.
AB  - Resins are produced by woody plants on a worldwide basis. We have found several
      distinct classes of modern diterpenoid resins based phenomenologically on the
      solid-state (13)C NMR spectra of the bulk material. Resin fossilizes over
      millions of years into a robust material sometimes called amber. We have
      characterized several hundred samples of fossil resin by solid-state (13)C NMR
      spectroscopy. We can relate one globe-spanning group of fossil resins to the
      modern genus Agathis, based on spectral evolution over time. A second large group
      has not been related with certainty to specific modern plants. Fossil resins from
      Europe fall into two categories, the famous Baltic ambers and another that
      resembles the Agathis group. Fossil resins from the Americas and Africa are
      closely related to the modern genus Hymenaea. Based on spectral distinctions,
      fossil resin found in an archaeological context sometimes can be assigned to a
      specific geographical origin on the basis of its (13)C NMR spectrum.

PMID- 12186568
TI  - Chronometric dating in archaeology: a review.
AB  - Most archaeological dating methods are based on decay of a naturally occurring
      radioisotope. (14)C activity of fossil bones and charcoal decreases with age, but
      must be calibrated for past changes in atmospheric activity. Uranium absorbed by
      shells and stalagmites is used to date on a 10(5)-year scale by observing the
      decay of (234)U to (230) Th. Thermoluminescence, optical luminescence, and
      electron spin resonance detect trapped electronic charges generated by natural
      radioactivity in burned flint, beach sands, shells, and tooth enamel. Rate of
      racemization of amino acids in fossil shells is constant at constant T, and age
      can be tracked from an increase in the D/L ratio.

PMID- 12186569
TI  - Here today, gone tomorrow? integrated experimentation and geochemical modeling in
      studies of archaeological diagenetic change.
AB  - The factors which influence the survival or otherwise of archaeological materials
      in the burial environment must be understood to allow systematic interpretation
      of the archaeological record. Studies of postdepositional change, or diagenesis,
      are therefore essential. The dynamic nature of terrestrial burial environments
      and the complexity of aqueous fluid-mediated transformation mechanisms have
      hindered detailed diagenetic research to date. The novel use of integrated
      experimental and geochemical modeling strategies has the potential to make
      progress toward a quantified understanding of the diagenesis of inorganic and
      bioinorganic archaeological materials. We describe current work that is
      attempting to develop this approach.

PMID- 12186570
TI  - Detecting past attempts to restore two important works of art.
AB  - Chemistry plays a fundamental role in the preservation of our heritage. Artistic
      and archaeological materials deteriorate over time due to their interaction with
      the environment, and human intervention can trigger unexpected deterioration
      pathways. Previous intervention can also sometimes obscure information regarding
      the original techniques or the materials used to execute the artwork. Our studies
      of past intervention and attempts to conserve the lunette of the church of Santa
      Maria la Vetere in Militello Val di Catania (Italy) and Donatello's carved marble
      panels of the pulpit of the Duomo of Prato (Italy) are discussed as two examples
      of how chemistry can provide guidance for conservators and fill gaps in the known
      life of works of art.

PMID- 12186572
TI  - Archaeological contributions of skeletal lead analysis.
AB  - We developed a chemical method to quantitate lead in small skeletal specimens and
      used it to establish lead distribution and quantitation in modern skeletons for
      all age groups to standardize sampling sites. Application of the method to
      excavated ancient skeletal collections enabled prediction of socioeconomic status
      among Colonial Americans, as well as identification of lead poisoning in ancient
      Rome as related to lead production and in an 18th century Caribbean epidemic as
      related to distillation of rum. Depending upon the conditions of burial, bones
      may be contaminated by surrounding material. This can be a limiting factor for
      interpretation of lead levels, but multielement analysis and procedural
      modifications can permit continuing application of bone lead analysis to
      appropriately selected archaeological skeletal collections.

PMID- 12186571
TI  - Chemistry of archaeological animal fats.
AB  - Animal fats are preserved at archaeological sites in association with unglazed
      pottery, human and animal remains, and other deposits or hoards. High-temperature
      gas chromatography (HT-GC) and combined HT-GC/mass spectrometry (HT-GC/MS) has
      confirmed the presence of animal fats in lipid extracts of artifacts. Degradation
      products and pathways have been discerned through the analyses of archaeological
      finds and the products of laboratory and field-based decay experiments. The
      origins of preserved fats have been determined through detailed compositional
      analysis of their component fatty acids by GC, by GC/MS of dimethyl disulfide
      derivatives of monoenoic components, and by GC-combustion-isotope ratio-MS (GC-C
      IRMS), to derive diagenetically robust delta(13)C values. Regiospecific analysis
      of intact triacylglycerols by high-performance liquid chromatography/MS
      (HPLC/MS), with atmospheric pressure chemical ionization, provides a further
      criterion for establishing the origin of fats. Preparative GC has been employed
      to isolate individual fatty acids from archaeological pottery in sufficient
      amounts for (14)C dating.

PMID- 12186573
TI  - The genetic secrets some fossils hold.
AB  - Most animals that once lived have gone extinct. The remains of a few of these can
      be found in museum collections worldwide. As modern evolutionary biology is
      limited to the use of extant taxa, retrieving DNA from extinct or subfossil
      organisms can add significant insight into past population history and resolve
      phylogenies that can be tentative by morphology alone. DNA is a relatively weak
      molecule, comparatively speaking, yet under certain conditions it persists in the
      fossil record, despite what in vitro chemistry predicts. While most fossil
      remains do not contain DNA, museum specimens can be screened for the presence of
      conditions that would be conducive for nucleic acid preservation by measuring the
      extent of amino acid racemization and by looking at the extent of protein
      hydrolysis by pyrolysis gas chromatography/mass spectrometry. Results from these
      types of analyses suggest that the preservation of DNA is linked to the
      temperature and its constancy at a site rather than its age. Chemical analyses of
      coprolites from extinct herbivores from the late Pleistocene, as well as Archaic
      Native Americans, show the presence of compounds from the Maillard reaction. Upon
      the cleaving of these products, the defecator can be identified and his diet
      analyzed.

PMID- 12186574
TI  - Two new empirically derived reasons to use the assessment of basic learning
      abilities.
AB  - The Assessment of Basic Learning Abilities (ABLA) comprises six levels of
      hierarchically ordered visual and auditory-visual discriminations. Scores on the
      ABLA, Vineland Adaptive Behavior Scales, and the Wechsler Intelligence Scale
      Revised were obtained for 30 participants selected using a stratified random
      sample (i.e., by level of mental retardation) from 499 people served by a state
      center. Two noteworthy findings were (a) that correlations between the Vineland
      domains and the ABLA were all significant and ranged between .65 and .73, and (b)
      no participant performing below ABLA Level 6 was testable on the WAIS-R. Thus,
      Level 6 can be used as an efficient screen to determine the testability of this
      population on standardized intelligence tests. Implications for practitioners are
      discussed.

PMID- 12186575
TI  - A dynamic test to assess learning capacity in people with severe impairments.
AB  - Because traditional intelligence tests do not allow a reliable and valid estimate
      of the general cognitive abilities of individuals with IQs lower than 55, a
      dynamic test of analogical reasoning (Analogical Reasoning Learning Test-ARLT)
      was constructed for use with this population. The aim of the test is to
      distinguish individuals who could undergo more ambitious schooling and cognitive
      training from those who would profit little or none from such an intervention.
      Internal consistency and test-retest reliability of this measure are high.
      Discriminant and predictive validity, assessed with another learning test and
      with a one-month training on inductive reasoning, respectively, are satisfactory.
      The test is seen as a useful tool for diagnostic differentiation among low
      performers.

PMID- 12186576
TI  - Promoting the social acceptance of young children with moderate-severe
      intellectual disabilities using cooperative-learning techniques.
AB  - The effects of a cooperative-learning program on the social acceptance of
      children with moderate to severe intellectual disabilities by young children
      without disabilities were examined. Children without disabilities were assigned
      to a cooperative-learning program or a social-contact program involved with the
      special class children or to a control (no classroom contact) condition.
      Significant pretest-posttest changes over a 10-week period in the cooperative
      learning context indicated that children without disabilities gave the special
      class children higher peer acceptance ratings, greater popularity indices, and
      lower social-distance ratings. There were also more frequent interactions with
      the children without disabilities. These changes did not occur in either the
      social-contact or the control groups.

PMID- 12186577
TI  - Physical activity, dietary intake, and the insulin resistance syndrome in
      nondiabetic adults with mental retardation.
AB  - The association between physical activity, dietary behaviors, and elevated
      cardiovascular disease risk factor components of the insulin resistance syndrome
      in adults with mental retardation was identified. Established clinical cutoff
      points were used to identify 145 participants with mild mental retardation and
      hyperinsulinemia, borderline high triglycerides, low high-density lipoprotein
      cholesterol, hypertension, and abdominal obesity. Odds ratios were calculated
      from logistic regression analysis. Those who participated in more frequent bouts
      of physical activity or who consumed lower dietary fat intakes were approximately
      one third as likely to have hyperinsulinemia and abdominal obesity compared to
      those who participated in less frequent physical activity or who consumed higher
      fat intakes, suggesting that these behaviors are protective against elevated
      components of the insulin resistance syndrome.

PMID- 12186578
TI  - Benzodiazepine behavioral side effects: review and implications for individuals
      with mental retardation.
AB  - Behavioral side effects associated with benzodiazepines (such as clonazepam,
      diazepam, and lorazepam) are an easily overlooked and underrecognized problem
      with individuals who have mental retardation and can be inadvertently confused
      with other behavioral or psychiatric conditions. Based upon a literature review,
      behavioral side effects occurred for 13.0% of 446 individuals with mental
      retardation who were prescribed benzodiazepines for either behavioral or
      psychiatric conditions (n = 138, 17.4%), epilepsy (n = 208, 15.4%), or other
      medical conditions such as myoclonus or cerebral palsy (n = 100, 2.0%).
      Behavioral side effects for individual benzodiazepines for which data were
      available ranged from 11.4% to 25.0%. Implications of nonrecognition are
      discussed, and clinical indicators suggesting review by appropriate medical
      personnel are provided.

PMID- 12186579
TI  - A piece of my mind: cries and whiskers.

PMID- 12186581
TI  - Gene studies provide window on cancer prognosis, treatment benefits, toxic
      effects.

PMID- 12186580
TI  - Preserving privacy, preventing discrimination becomes the province of genetics
      experts.

PMID- 12186582
TI  - Psychosocial support for far-flung astronauts.

PMID- 12186588
TI  - Clinical manifestations of acute aortic dissection.

PMID- 12186590
TI  - Breastfeeding and later intelligence.

PMID- 12186591
TI  - Breastfeeding and later intelligence.

PMID- 12186593
TI  - Pollution-related mortality and educational level.

PMID- 12186595
TI  - Interpreting the number needed to treat.

PMID- 12186596
TI  - Interpreting the number needed to treat.

PMID- 12186598
TI  - Funding priorities for medical research.

PMID- 12186600
TI  - Ginkgo for memory enhancement: a randomized controlled trial.
AB  - CONTEXT: Several over-the-counter treatments are marketed as having the ability
      to improve memory, attention, and related cognitive functions in as little as 4
      weeks. These claims, however, are generally not supported by well-controlled
      clinical studies. OBJECTIVE: To evaluate whether ginkgo, an over-the-counter
      agent marketed as enhancing memory, improves memory in elderly adults as measured
      by objective neuropsychological tests and subjective ratings. DESIGN: Six-week
      randomized, double-blind, placebo-controlled, parallel-group trial. SETTING AND
      PARTICIPANTS: Community-dwelling volunteer men (n = 98) and women (n = 132) older
      than 60 years with Mini-Mental State Examination scores greater than 26 and in
      generally good health were recruited by a US academic center via newspaper
      advertisements and enrolled over a 26-month period from July 1996 to September
      1998. INTERVENTION: Participants were randomly assigned to receive ginkgo, 40 mg
      3 times per day (n = 115), or matching placebo (n = 115). MAIN OUTCOME MEASURES:
      Standardized neuropsychological tests of verbal and nonverbal learning and
      memory, attention and concentration, naming and expressive language, participant
      self-report on a memory questionnaire, and caregiver clinical global impression
      of change as completed by a companion. RESULTS: Two hundred three participants
      (88%) completed the protocol. Analysis of the modified intent-to-treat population
      (all 219 participants returning for evaluation) indicated that there were no
      significant differences between treatment groups on any outcome measure. Analysis
      of the fully evaluable population (the 203 who complied with treatment and
      returned for evaluation) also indicated no significant differences for any
      outcome measure. CONCLUSIONS: The results of this 6-week study indicate that
      ginkgo did not facilitate performance on standard neuropsychological tests of
      learning, memory, attention, and concentration or naming and verbal fluency in
      elderly adults without cognitive impairment. The ginkgo group also did not differ
      from the control group in terms of self-reported memory function or global rating
      by spouses, friends, and relatives. These data suggest that when taken following
      the manufacturer's instructions, ginkgo provides no measurable benefit in memory
      or related cognitive function to adults with healthy cognitive function.

PMID- 12186601
TI  - Impact of cataract surgery on motor vehicle crash involvement by older adults.
AB  - CONTEXT: Motor vehicle crash risk in older drivers is elevated in those with
      cataract, a condition that impairs vision and is present in half of adults aged
      65 years or older. OBJECTIVE: To determine the impact of cataract surgery on the
      crash risk for older adults in the years following surgery, compared with that of
      older adults who have cataract but who elect to not have surgery. DESIGN,
      SETTING, AND PATIENTS: Prospective cohort study of 277 patients with cataract,
      aged 55 to 84 years at enrollment, who were recruited from 12 eye clinics in
      Alabama from October 1994 through March 1996, with 4 to 6 years of follow-up (to
      March 1999). MAIN OUTCOME MEASURE: Police-reported motor vehicle crash occurrence
      involving patients who elected to have surgery compared with those who did not.
      RESULTS: Comparing the cataract surgery group (n = 174) with the no surgery group
      (n = 103), the rate ratio for crash involvement was 0.47 (95% confidence
      interval, 0.23-0.94), adjusting for race and baseline visual acuity and contrast
      sensitivity. The absolute rate reduction associated with cataract surgery was
      4.74 crashes per million miles of travel. CONCLUSIONS: In our sample, patients
      with cataract who underwent cataract surgery and intraocular lens implantation
      had half the rate of crash involvement during the follow-up period compared with
      cataract patients who did not undergo surgery. Cataract surgery thus may have a
      previously undocumented benefit for older driver safety, reducing subsequent
      crash rate.

PMID- 12186602
TI  - Changes in methadone treatment practices: results from a national panel study,
      1988-2000.
AB  - CONTEXT: Results from several studies conducted in the early 1990s showed that
      the majority of US methadone maintenance programs did not use treatment practices
      that met established standards for the care of heroin users. Effective treatment
      for heroin users is critical given the upsurge in heroin use and the continued
      role of injection drug use in the human immunodeficiency virus and hepatitis C
      epidemics. OBJECTIVES: To examine the extent to which US methadone maintenance
      treatment programs have made changes in the past 12 years to provide adequate
      methadone doses and to identify factors associated with variation in program
      performance. DESIGN, SETTING, AND PARTICIPANTS: Program directors and clinical
      supervisors of nationally representative methadone treatment programs that varied
      by ownership (for-profit, public, or private not-for-profit) and setting (eg,
      free-standing, hospital-based) were surveyed in 1988 (n = 172), 1990 (n = 140),
      1995 (n = 116), and 2000 (n = 150). MAIN OUTCOME MEASURES: Percentage of patients
      in each treatment program receiving methadone dosages of less than 40, 60, and 80
      mg/d. RESULTS: The percentage of patients receiving methadone dosage levels less
      than the recommended 60 mg/d has decreased from 79.5% in 1988 to 35.5% in 2000.
      Results also show that programs with a greater percentage of African American
      patients are especially likely to dispense low dosages, while programs with Joint
      Commission on Accreditation of Healthcare Organizations accreditation are more
      likely to provide adequate methadone doses. CONCLUSIONS: Efforts to improve
      methadone treatment practices appear to be making progress, but many patients are
      still receiving substandard care.

PMID- 12186603
TI  - Conditioning and hyperalgesia in newborns exposed to repeated heel lances.
AB  - CONTEXT: Hospitalized infants undergo repeated invasive procedures. It is unknown
      whether cumulative experiences with pain lead to anticipatory pain behaviors and
      hyperalgesia. OBJECTIVES: To determine whether newborns who are born to mothers
      with diabetes and undergo repeated pain learn to anticipate pain and exhibit more
      pain during a painful procedure than normal infants. DESIGN, SETTING, AND
      PARTICIPANTS: Prospective cohort study of 21 full-term newborns born to mothers
      with diabetes and 21 born to mothers with uneventful pregnancies, at a university
      teaching hospital between August 1999 and October 2000. Infants of diabetic
      mothers underwent repeated heel lances in the first 24 to 36 hours of life for
      monitoring of blood glucose concentrations. Pain responses of all infants
      undergoing a venipuncture on the dorsum of the hand to obtain blood for the
      newborn screening test after the first day of life were compared. In addition,
      from September through November 2001, 12 infants of diabetic mothers and 12
      normal infants were compared for pain reactions to intramuscular vitamin K
      injection after birth. MAIN OUTCOME MEASURES: Percentages of time observed
      grimacing and crying and visual analog scale (VAS) scores. RESULTS: Raters were
      blinded to exposure group. Median baseline scores for grimacing, crying time, and
      VAS did not differ significantly between groups (P =.27, P =.32, and P =.32,
      respectively). Median scores (interquartile range) for grimacing during skin
      cleansing were higher in infants of diabetic mothers (22.2% [77.5%] vs 0% [15%];
      P =.03). The VAS scores for both groups were zero, but the distribution of the
      scores was significantly different (86% of normal infants vs 52% of infants of
      diabetic mothers had scores of zero) (P =.04). During venipuncture, infants of
      diabetic mothers had higher median scores for grimacing (81.7% [32.5%] vs 40%
      [73.4%]; P =.01), VAS (69% [27.5%] vs 5% [60.5%]; P =.002), and crying (40.2%
      [77%] vs 0% [54.8%]; P =.03) compared with normal infants. There were no
      differences between groups on any pain measure in response to intramuscular
      injection. CONCLUSIONS: Newborns who had diabetic mothers and were exposed to
      repeated heel lances in the first 24 to 36 hours of life learned to anticipate
      pain and exhibited more intense pain responses during venipuncture than normal
      infants.

PMID- 12186604
TI  - Effect of treatment with low doses of hydrocortisone and fludrocortisone on
      mortality in patients with septic shock.
AB  - CONTEXT: Septic shock may be associated with relative adrenal insufficiency.
      Thus, a replacement therapy of low doses of corticosteroids has been proposed to
      treat septic shock. OBJECTIVE: To assess whether low doses of corticosteroids
      improve 28-day survival in patients with septic shock and relative adrenal
      insufficiency. DESIGN AND SETTING: Placebo-controlled, randomized, double-blind,
      parallel-group trial performed in 19 intensive care units in France from October
      9, 1995, to February 23, 1999. PATIENTS: Three hundred adult patients who
      fulfilled usual criteria for septic shock were enrolled after undergoing a short
      corticotropin test. INTERVENTION: Patients were randomly assigned to receive
      either hydrocortisone (50-mg intravenous bolus every 6 hours) and fludrocortisone
      (50- micro g tablet once daily) (n = 151) or matching placebos (n = 149) for 7
      days. MAIN OUTCOME MEASURE: Twenty-eight-day survival distribution in patients
      with relative adrenal insufficiency (nonresponders to the corticotropin test).
      RESULTS: One patient from the corticosteroid group was excluded from analyses
      because of consent withdrawal. There were 229 nonresponders to the corticotropin
      test (placebo, 115; corticosteroids, 114) and 70 responders to the corticotropin
      test (placebo, 34; corticosteroids, 36). In nonresponders, there were 73 deaths
      (63%) in the placebo group and 60 deaths (53%) in the corticosteroid group
      (hazard ratio, 0.67; 95% confidence interval, 0.47-0.95; P =.02). Vasopressor
      therapy was withdrawn within 28 days in 46 patients (40%) in the placebo group
      and in 65 patients (57%) in the corticosteroid group (hazard ratio, 1.91; 95%
      confidence interval, 1.29-2.84; P =.001). There was no significant difference
      between groups in responders. Adverse events rates were similar in the 2 groups.
      CONCLUSION: In our trial, a 7-day treatment with low doses of hydrocortisone and
      fludrocortisone significantly reduced the risk of death in patients with septic
      shock and relative adrenal insufficiency without increasing adverse events.

PMID- 12186605
TI  - Postmenopausal hormone replacement therapy: scientific review.
AB  - CONTEXT: Although postmenopausal hormone replacement therapy (HRT) is widely used
      in the United States, new evidence about its benefits and harms requires
      reconsideration of its use for the primary prevention of chronic conditions.
      OBJECTIVE: To assess the benefits and harms of HRT for the primary prevention of
      cardiovascular disease, thromboembolism, osteoporosis, cancer, dementia, and
      cholecystitis by reviewing the literature, conducting meta-analyses, and
      calculating outcome rates. DATA SOURCES: All relevant English-language studies
      were identified in MEDLINE (1966-2001), HealthSTAR (1975-2001), Cochrane Library
      databases, and reference lists of key articles. Recent results of the Women's
      Health Initiative (WHI) and the Heart and Estrogen/progestin Replacement Study
      (HERS) are included for reported outcomes. STUDY SELECTION AND DATA EXTRACTION:
      We used all published studies of HRT if they contained a comparison group of HRT
      nonusers and reported data relating to HRT use and clinical outcomes of interest.
      Studies were excluded if the population was selected according to prior events or
      presence of conditions associated with higher risks for targeted outcomes. DATA
      SYNTHESIS: Meta-analyses of observational studies indicated summary relative
      risks (RRs) for coronary heart disease (CHD) incidence and mortality that were
      significantly reduced among current HRT users only, although risk for incidence
      was not reduced when only studies that controlled for socioeconomic status were
      included. The WHI reported increased CHD events (hazard ratio [HR], 1.29; 95%
      confidence interval [CI], 1.02-1.63). Stroke incidence but not mortality was
      significantly increased among HRT users in the meta-analysis and the WHI. The
      meta-analysis indicated that risk was significantly elevated for thromboembolic
      stroke (RR, 1.20; 95% CI, 1.01-1.40) but not subarachnoid or intracerebral
      stroke. Risk of venous thromboembolism among current HRT users was increased
      overall (RR, 2.14; 95% CI, 1.64-2.81) and was highest during the first year of
      use (RR, 3.49; 95% CI, 2.33-5.59) according to a meta-analysis of 12 studies.
      Protection against osteoporotic fractures is supported by a meta-analysis of 22
      estrogen trials, cohort studies, results of the WHI, and trials with bone density
      outcomes. Current estrogen users have an increased risk of breast cancer that
      increases with duration of use. Endometrial cancer incidence, but not mortality,
      is increased with unopposed estrogen use but not with estrogen with progestin. A
      meta-analysis of 18 observational studies showed a 20% reduction in colon cancer
      incidence among women who had ever used HRT (RR, 0.80; 95% CI, 0.74-0.86), a
      finding supported by the WHI. Women symptomatic from menopause had improvement in
      certain aspects of cognition. Current studies of estrogen and dementia are not
      definitive. In a cohort study, current HRT users had an age-adjusted RR for
      cholecystitis of 1.8 (95% CI, 1.6-2.0), increasing to 2.5 (95% CI, 2.0-2.9) after
      5 years of use. CONCLUSIONS: Benefits of HRT include prevention of osteoporotic
      fractures and colorectal cancer, while prevention of dementia is uncertain. Harms
      include CHD, stroke, thromboembolic events, breast cancer with 5 or more years of
      use, and cholecystitis.

PMID- 12186606
TI  - Assessing benefits and harms of hormone replacement therapy: clinical
      applications.
AB  - An estimated one third of postmenopausal women in the United States use hormone
      replacement therapy (HRT) to treat symptoms of menopause and prevent chronic
      conditions. In the context of this widespread use, evidence has been growing
      about the potential harms of HRT, particularly regarding long-term use.
      Physicians and patients are often confused about how to use results of studies in
      individual cases. This article applies the current state of evidence for the
      benefits and harms of HRT to management decisions in 4 clinical situations.
      Patient preferences, as well as evidence, are important for these decisions.
      Benefits and harms need to be readdressed periodically to apply newly published
      evidence and to reassess emerging risks, comorbidities, and needs of individuals.

PMID- 12186607
TI  - Cataract surgery and motor vehicle crashes--proceed with caution.

PMID- 12186608
TI  - Corticosteroids and septic shock.

PMID- 12186609
TI  - A primary care home for Americans: putting the house in order.
AB  - This article--the first in a series on primary care--outlines the daunting
      challenges facing primary care today. Most people in the United States desire a
      primary care "home" to provide for and coordinate their health care needs. Yet
      primary care is endangered by physician stress, inadequate performance in
      managing chronic illness, and inability to provide prompt access and reliable
      continuity of care. Fundamental redesign is needed to improve access to and
      quality of care while easing physicians' workload without causing major increases
      in health care costs.

PMID- 12186615
TI  - The pharmacoeconomic impact of generics: an evolutionary tale.
AB  - The very word generics stiffens sinews and tightens lips in the pharma industry.
      It has been proposed that large profits and much pride are now being lost through
      the creeping forces of intellectual piracy and generic plagiarism [1-3]. In this
      article, I will argue against this position. Using models from evolution and
      modern day complexity theory I will attempt to address some of the fears that
      surround generic pharmaceutical enterprise and to express my own concerns about
      some of the overly optimistic thinking that occurs with respect to developing
      world systems and the HIV virus.

PMID- 12186616
TI  - Economic evaluation in evidence-based practice.
AB  - The economic evaluation of health care interventions and technologies is an
      essential part of any modern healthcare system. In recent years a growing demand
      for information about the economic benefits of healthcare technologies has seen a
      significant increase in the number of published economic evaluations of
      healthcare. Economic evaluation reviews have demonstrated considerable
      methodological flaws in a significant number of analyses in health care. Widely
      accepted guidance regarding the manner in which multinational economic
      evaluations should be designed, analysed and presented is still awaited. The main
      types of economic analyses are described in this article, providing a framework
      along which to evaluate them.

PMID- 12186617
TI  - Pharmacoeconomics of cisplatin-based chemoradiation in cervical cancer: a review.
AB  - Is the use of cisplatin-based chemoradiation therapy, which has become the new
      standard of care for locally-advanced cervical cancer, cost-effective? To
      evaluate this, a pharmacoeconomic analysis of five recent Phase III trials of
      cisplatin-based chemoradiation for the treatment of locally-advanced cervical
      cancer was conducted. Using an economic model, we applied cost data to resource
      use data derived from the cisplatin-based chemoradiation arms of these randomised
      trials. We examined the cisplatin-based chemoradiation benefits in terms of
      increased median survival time. Incremental costs were divided by the difference
      in survival to determine the cost per patient benefited. Cost per life-year
      gained were calculated based on both published survival and estimated survival.
      Costs of cisplatin-based chemoradiation therapy regimens per life-year gained
      varied from US$2709 - 27,882 based on published survival and US$350 - 2860 based
      on estimated survival. Variations in regimen cost were largely dependent on in
      patient or out-patient administration costs. Costs for cisplatin and 5
      flourouracil were US$10,037 per in-patient compared to US$3431 for out-patient
      treatment. In conclusion, cisplatin-based chemoradiation regimens increased mean
      survival at an acceptable cost per life-year gained in both the in-patient and
      out-patient settings.

PMID- 12186618
TI  - Evaluation and cost assessment of fluoroquinolones in community-acquired
      respiratory infections.
AB  - Several new fluoroquinolones have been marketed since the late 1990s.
      Fluoroquinolones are an effective treatment for most community-acquired
      respiratory tract infections, including acute sinusitis, acute exacerbations of
      chronic bronchitis and community-acquired pneumonia. However, other antibiotics,
      including beta-lactams, macrolides, tetracyclines and trimethoprim
      sulfamethoxazole, are also effective against these respiratory infections. From a
      managed care perspective, it is the subtle differences between the drugs in the
      eradication of bacterial pathogens, adverse effects, dose regimens, compliance
      issues, bacterial resistance and cost that determine the best choice for the
      management of pneumonia, sinusitis or exacerbations of chronic bronchitis. The
      potential for bacterial resistance is perhaps the only significant barrier to
      extensive fluoroquinolone use in community-acquired respiratory tract infections.
      Cost-effectiveness must be balanced with quality care, both from an individual
      perspective and that of the greater society.

PMID- 12186619
TI  - Pharmacoeconomic considerations in anaesthetic use.
AB  - Healthcare costs are rising in all areas of medicine, especially in high
      technology specialities such as anaesthesia. Therefore, cost containment and
      reduction have become major goals in many hospitals and anaesthesia departments.
      One area that has received substantial attention is the cost of pharmaceutical
      products, in particular the cost of newer, shorter-acting inhaled and intravenous
      anaesthetics, analgesics and neuromuscular blocking agents. Numerous
      pharmacoeconomic studies have been published on the theoretical analysis of
      anaesthetic drug costs and the potential benefit of various anaesthesia
      techniques. However, the results are not conclusive and anaesthesia departments
      continue to seek ways to reduce costs. In this review, we intend to discuss cost
      terminology, common areas of cost containment in anaesthesia and the relationship
      of anaesthesia care costs to total perioperative costs.

PMID- 12186620
TI  - G-CSF as prophylaxis of febrile neutropenia in SCLC.
AB  - OBJECTIVES: In 1991, small cell lung cancer (SCLC) was reported as the first
      tumour type where colony stimulating factor (CSF) support was clinically
      effective. We reviewed 13 health services research studies that addressed CSF use
      as supportive care for SCLC. METHODS: Findings from American Society of Clinical
      Oncology (ASCO) membership surveys, patterns of care studies, ASCO evidence-based
      guidelines and cost-effectiveness studies for CSF use were reviewed. RESULTS: For
      primary prophylaxis for SCLC, ASCO CSF clinical guidelines clearly do not support
      granulocyte (G)-CSF use. Cost-effectiveness models indicate that CSF use in this
      setting is associated with as much as US$1900 incremental patient care costs per
      cycle given an 18% febrile neutropenia rate. ASCO membership surveys found that <
      10% of respondents supported CSF as primary prophylaxis while a patterns-of-care
      study found 55% use. In the secondary prophylaxis setting, ASCO CSF guidelines in
      1994, 1996 and 1997 were equally supportive of CSF use versus dose reduction but
      dose-reduction was considered the preferred option in 2000. Over half of the ASCO
      member respondents in 1994 and in 1997 supported G-CSF use; cost-effectiveness
      models indicated that CSF use incurred an additional US$144 and 277 per cycle and
      the patterns of care study found 27% use of CSF in the community practice
      setting. CONCLUSIONS: In 2002, the findings of a decade of health services
      studies have shifted towards not being supportive of CSF use for primary or
      secondary prophylaxis for SCLC patients.

PMID- 12186621
TI  - Tuberculosis therapy and telemedicine.
AB  - Directly observed therapy (DOT) ensures patient adherence through the
      administration of medications by trained health department personnel. This
      approach has been widely adopted in tuberculosis care. Unfortunately, DOT
      programs require a substantial commitment of scarce public health funds and
      personnel time. The application of telemedicine to DOT promises considerable cost
      and time savings.

PMID- 12186622
TI  - Adverse drug reactions: current issues and strategies for prevention and
      management.
AB  - Adverse drug reactions (ADRs) are common, frequently serious and cause
      considerable morbidity and mortality. In addition to human costs, ADRs place
      considerable economic burden on society and already-stretched healthcare systems.
      Much work has been done to determine potential causes, commonly responsible drugs
      and susceptible patient groups. To this end, various national pharmacovigilance
      schemes exist to collate information about ADRs. Despite this, levels of ADR
      reporting are universally poor, with ADRs remaining a significant clinical
      problem. Therefore, more effective dissemination and implementation of available
      knowledge is needed, together with better use of the systems already in place.
      Local ADR centres and teams, in close liaison with national centres, appear to be
      an important part of this process and need to be developed within healthcare
      systems. In addition, there is now evidence to suggest that better use of
      informatics will help to facilitate this, together with wider availability of
      electronic notes and greater use of computer-prescribing. Although advancing
      technology may help to make the use of medicines safer, more effective and more
      specific in the future, investment to develop informatics infrastructure and
      local ADR teams is now needed in our healthcare systems.

PMID- 12186623
TI  - Alternative and rescue treatment regimens for Helicobacter pylori eradication.
AB  - Eradication therapy has been incorporated into clinical practice. The regimens
      currently recommended for first-line treatment include a 2-week bismuth-based
      triple therapy (mainly in developing countries), a 1 - 2 week proton pump
      inhibitor (PPI)-based triple therapy and a 1-week ranitidine bismuth citrate
      (RBC)-based triple therapy. However, these regimens fail to eradicate
      Helicobacter pylori in up to 20% of patients due to poor compliance, inadequate
      treatment duration, smoking, old age and bacterial resistance to nitroimidazoles
      and/or macrolides in particular. Therefore, alternative regimens that avoid
      nitroimidazoles and/or macrolides or overcome bacterial resistance to these
      drugs, improve compliance, minimise side effects and/or reduce costs have been
      evaluated. One-week quadruple therapy, which adds a PPI or histamine receptor 2
      blocker to bismuth-based triple therapy, usually achieves an eradication rate of
      90% when used as an alternative first-line therapy but the efficacy decreases
      when used as a rescue therapy. Several new triple therapies that may be used as
      alternative and/or rescue therapies have been evaluated. Among these are
      furazolidone-based (furazolidone plus an antibiotic and a bismuth salt, a PPI or
      RBC), fluoroquinolone-based (levofloxacin or moxifloxacin plus an antibiotic and
      a PPI) and ecabet sodium-based (ecabet plus two antibiotics) triple therapies.
      Recently, rifabutin has been used in combination with a PPI and amoxycillin as a
      rescue therapy, with satisfactory eradication rates. In addition, a number of new
      antimicrobial agents are currently under investigation in in vitro studies but
      the clinical values of these agents needs to be confirmed.

PMID- 12186624
TI  - An evaluation of bicalutamide in the treatment of prostate cancer.
AB  - Prostate cancer is a major health problem in men, causing significant morbidity
      and mortality. Although traditionally considered a disease of old age, improved
      diagnostic techniques have resulted in earlier diagnosis and many men are now
      treated while still physically and sexually active. Current therapies for
      prostate cancer, which include medical or surgical castration, have a significant
      impact on many aspects of quality of life. The non-steroidal antiandrogen
      bicalutamide (Casodex, AstraZeneca) has a favourable tolerability profile with
      demonstrated efficacy in several stages of prostate cancer and represents an
      alternative therapeutic strategy to castration. Mature survival data from men
      with previously untreated, locally-advanced disease reveal that bicalutamide
      monotherapy provides survival benefits that do not differ significantly from
      castration, while offering important advantages with respect to the maintenance
      of physical capacity and sexual interest. Recent data from a prospective
      randomised trial, the largest prostate cancer treatment study ever conducted,
      demonstrate that immediate therapy with bicalutamide (alone or as an adjuvant to
      therapy of curative intent) significantly reduces the risk of objective disease
      progression in patients with localised or locally-advanced prostate cancer.
      Antiandrogens are also used in combination with castration (combined androgen
      blockade) for advanced disease. Another large, randomised trial demonstrated that
      combined androgen blockade with bicalutamide is associated with a similar
      survival outcome to combined androgen blockade with flutamide and is better
      tolerated. The evidence reviewed demonstrates that bicalutamide currently has a
      favourable risk:benefit ratio in several stages of prostate cancer. The role of
      bicalutamide will be further defined by ongoing studies.

PMID- 12186625
TI  - Anastrozole in the management of breast cancer.
AB  - Anastrozole (Arimidex, AstraZeneca) is a third-generation aromatase inhibitor
      which rapidly reduces oestradiol concentrations to below detectable levels. It is
      both potent and selective for the aromatase enzyme, with near-maximal suppression
      of serum oestrogens occurring at the clinical dose of 1 mg/day in postmenopausal
      women with advanced breast cancer. Anastrozole has also been shown to be a potent
      suppressor of intratumoural oestrogens, with responses comparable to those in
      serum. The results of two large, identically designed, randomised trials in
      postmenopausal women with advanced breast cancer who had progressed on tamoxifen
      showed that oral anastrozole 1 mg/day produced a statistically significant
      survival advantage over megestrol acetate 40 mg q.i.d. The median duration of
      survival was 26.7 months for anastrozole versus 22.5 months for megestrol
      acetate. Anastrozole was as well-tolerated as megestrol acetate, while weight
      gain was significantly increased in the megestrol acetate group compared with the
      anastrozole group. In another Phase III clinical trial involving 1021
      postmenopausal women with advanced breast cancer, anastrozole showed a
      statistically significant advantage over tamoxifen in median time to progression
      in a combined analysis of 611 patients who were known to be oestrogen receptor-
      or progesterone receptor-positive. Anastrozole was as well-tolerated as
      tamoxifen, with a low rate of withdrawals (2%) due to drug-related adverse
      events. In addition, anastrozole was associated with fewer thromboembolic events
      and episodes of vaginal bleeding than tamoxifen. For women with hormone receptor
      positive tumours who progress on tamoxifen, anastrozole is superior to megestrol
      acetate. In addition, anastrozole is a reasonable alternative to tamoxifen for
      first-line endocrine therapy of advanced breast cancer. Recent data confirm an
      emerging role for anastrozole as adjuvant therapy for primary breast cancer in
      postmenopausal patients. Anastrozole is also being investigated in the
      neoadjuvant setting.

PMID- 12186626
TI  - Quinupristin/dalfopristin.
AB  - Gram-positive pathogens are associated with both community- and hospital-acquired
      infections. These infections may be life-threatening in hospitalised patients,
      especially in those with significant underlying acute or chronic diseases. Prompt
      and appropriate antimicrobial therapy is essential for avoiding morbidity and
      mortality. The concept of appropriate therapy is being redefined by increasing
      antimicrobial resistance, especially amongst Gram-positive pathogens. This has
      been most dramatic with penicillin-resistant Streptococcus pneumoniae in the
      community, including cross-resistance to other classes of antimicrobial agents.
      In the US, the incidence of methicillin-resistant Staphylococcus aureus (MRSA)
      with community isolates is significant. For hospital-acquired Gram-positive
      pathogens, MRSA, vancomycin-resistant Enterococcus species and vancomycin
      intermediate resistant and -resistant S. aureus are a great concern, particularly
      as the frequency of recovery of these pathogens from infected patients increases.
      The net result of these various resistance issues is a reduction in the number of
      appropriate antimicrobial agents for treating infected patients.
      Quinupristin/dalfopristin is a parental streptogramin with a spectrum of activity
      that includes Gram-positive pathogens, including those resistant to other classes
      of antimicrobial compounds. In this review, data summarising the frequency of
      recovered Gram-positive pathogens from various infectious diseases, the
      escalating prevalence of resistance amongst Gram-positive pathogens and the
      factors making quinupristin/dalfopristin a suitable agent for treating patients
      infected with Gram-positive organisms will be discussed.

PMID- 12186627
TI  - Interactions between two fission yeast serine/arginine-rich proteins and their
      modulation by phosphorylation.
AB  - The unexpected low number of genes in the human genome has triggered increasing
      attention to alternative pre-mRNA splicing, and serine/arginine-rich (SR)
      proteins have been correlated with the complex alternative splicing that is a
      characteristic of metazoans. SR proteins interact with RNA and splicing protein
      factors, and they also undergo reversible phosphorylation, thereby regulating
      constitutive and alternative splicing in mammals and Drosophila. However, it is
      not clear whether the features of SR proteins and alternative splicing are
      present in simple and genetically tractable organisms, such as yeasts. In the
      present study, we show that the SR-like proteins Srp1 and Srp2, found in the
      fission yeast Schizosaccharomyces pombe, interact with each other and the
      interaction is modulated by protein phosphorylation. By using Srp1 as bait in a
      yeast two-hybrid analysis, we specifically isolated Srp2 from a random screen.
      This Srp interaction was confirmed by a glutathione-S-transferase pull-down
      assay. We also found that the Srp1-Srp2 complex was phosphorylated at a reduced
      efficiency by a fission yeast SR-specific kinase, Dis1-suppression kinase (Dsk1).
      Conversely, Dsk1-mediated phosphorylation inhibited the formation of the Srp
      complex. These findings offer the first example in fission yeast for interactions
      between SR-related proteins and the modulation of the interactions by specific
      protein phosphorylation, suggesting that a mammalian-like SR protein function may
      exist in fission yeast.

PMID- 12186628
TI  - Functional identity of Drosophila melanogaster Indy as a cation-independent,
      electroneutral transporter for tricarboxylic acid-cycle intermediates.
AB  - Indy is a gene in Drosophila melanogaster which, when made dysfunctional, leads
      to an extension of the average adult life span of the organism. The present study
      was undertaken to clone the Indy gene-product and to establish its functional
      identity. We isolated a full-length Indy cDNA from a D. melanogaster cDNA
      library. The cDNA codes for a protein of 572 amino acids [( Drosophila Indy
      (drIndy)]. In its amino acid sequence, drIndy exhibits comparable similarity to
      the two known Na(+)-coupled dicarboxylate transporters in mammals; namely, NaDC1
      (35% identity) and NaDC3 (34% identity). We elucidated the functional
      characteristics of drIndy in two different heterologous expression systems by
      using mammalian cells and Xenopus laevis oocytes. These studies show that drIndy
      is a cation-independent electroneutral transporter for a variety of tricarboxylic
      acid-cycle intermediates, with preference for citrate compared with succinate.
      These characteristics of drIndy differ markedly from those of NaDC1 and NaDC3,
      indicating that neither of these latter transporters is the mammalian functional
      counterpart of drIndy. Since drIndy is a transporter for tricarboxylic acid-cycle
      intermediates, dysfunction of the Indy gene may lead to decreased production of
      metabolic energy in cells, analogous to caloric restriction. This might provide
      the molecular basis for the observation that disruption of the Indy gene function
      in Drosophila leads to extension of the average adult life span of the organism.

PMID- 12186629
TI  - Diverse effects of two allosteric inhibitors on the phosphorylation state of
      glycogen phosphorylase in hepatocytes.
AB  - Two distinct allosteric inhibitors of glycogen phosphorylase, 1,4-dideoxy-1,4
      imino-D-arabinitol (DAB) and CP-91149 (an indole-2-carboxamide), were
      investigated for their effects on the phosphorylation state of the enzyme in
      hepatocytes in vitro. CP-91149 induced inactivation (dephosphorylation) of
      phosphorylase in the absence of hormones and partially counteracted the
      phosphorylation caused by glucagon. Inhibition of glycogenolysis by CP-91149 can
      be explained by dephosphorylation of phosphorylase a. This was associated with
      activation of glycogen synthase and stimulation of glycogen synthesis. DAB, in
      contrast, induced a small degree of phosphorylation of phosphorylase. This was
      associated with inactivation of glycogen synthase and inhibition of glycogen
      synthesis. Despite causing phosphorylation (activation) of phosphorylase, DAB is
      a very potent inhibitor of glycogenolysis in both the absence and presence of
      glucagon. This is explained by allosteric inhibition of phosphorylase a, which
      overrides the increase in activation state. In conclusion, two potent
      phosphorylase inhibitors exert different effects on glycogen metabolism in intact
      hepatocytes as a result of opposite effects on the phosphorylation state of both
      phosphorylase and glycogen synthase.

PMID- 12186630
TI  - Identification of in vitro and in vivo phosphorylation sites in the catalytic
      subunit of the DNA-dependent protein kinase.
AB  - The DNA-dependent protein kinase (DNA-PK) is required for the repair of DNA
      double-strand breaks (DSBs), such as those caused by ionizing radiation and other
      DNA-damaging agents. DNA-PK is composed of a large catalytic subunit (DNA-PKcs)
      and a heterodimer of Ku70 and Ku80 that assemble on the ends of double-stranded
      DNA to form an active serine/threonine protein kinase complex. Despite in vitro
      and in vivo evidence to support an essential role for the protein kinase activity
      of DNA-PK in the repair of DNA DSBs, the physiological targets of DNA-PK have
      remained elusive. We have previously shown that DNA-PK undergoes
      autophosphorylation in vitro, and that autophosphorylation correlates with loss
      of protein kinase activity and dissociation of the DNA-PK complex. Also,
      treatment of cells with the protein phosphatase inhibitor, okadaic acid, enhances
      DNA-PKcs phosphorylation and reduces DNA-PK activity in vivo. Here, using solid
      phase protein sequencing, MS and phosphospecific antibodies, we have identified
      seven in vitro autophosphorylation sites in DNA-PKcs. Six of these sites
      (Thr2609, Ser2612, Thr2620, Ser2624, Thr2638 and Thr2647) are clustered in a
      region of 38 amino acids in the central region of the protein. Five of these
      sites (Thr2609, Ser2612, Thr2638, Thr2647 and Ser3205) are conserved between six
      vertebrate species. Moreover, we show that DNA-PKcs is phosphorylated in vivo at
      Thr2609, Ser2612, Thr2638 and Thr2647 in okadaic acid-treated human cells. We
      propose that phosphorylation of these sites may play an important role in DNA-PK
      function.

PMID- 12186631
TI  - Identification of two domains and distal histidine ligands to the four haems in
      the bacterial c-type cytochrome NapC; the prototype connector between
      quinol/quinone and periplasmic oxido-reductases.
AB  - NapC is a tetra-haem member of a family of bacterial membrane-anchored multi-haem
      c -type cytochromes implicated in electron transfer between membrane quinols and
      periplasmic enzymes. The water-soluble tetra-haem fragment of Paracoccus
      pantotrophus NapC has been expressed as a periplasmic protein (NapC(sol)) in
      Paracoccus denitrificans, P. pantotrophus and Escherichia coli. Site-specific
      mutagenesis of NapC(sol), combined with spectroscopic studies, suggests that each
      haem iron centre has bis -histidinyl co-ordination. Four proximal ligands arise
      from each of four Cys-Xaa-Xaa-Cys-His haem-binding motifs; candidates for the
      four distal ligands are His(81), His(99), His(174) and His(194). NapC(H81A),
      NapC(H99A), NapC(H174A) and NapC(H194A) mutants (with alanine substituted for
      each of the four candidate residues) have all been purified from E. coli. In each
      case, one of the haems has become high-spin, as judged by the presence of a broad
      absorption band between 620 nm and 650 nm for the oxidized cytochrome; this
      feature is absent for wild-type protein and presumably arises because of the
      absence of the distal histidine ligand from one of the haems. NapC(H81A) and
      NapC(H174A) are less well expressed in E. coli than NapC(H99A) and NapC(H194A)
      and cannot be detected when expressed in P. denitrificans or P. pantotrophus. In
      vitro and in vivo complementation studies demonstrate that the soluble
      periplasmic NapC can mediate electron transfer from quinols to the periplasmic
      nitrate reductase. This capacity was retained in vitro with the NapC(H99A) and
      NapC(H194A) mutants but was lost in vivo. A model for the structural organization
      of NapC(sol) into two domains, each containing a di-haem pair, is proposed. In
      this model, each haem pair obtains one distal haem ligand from its own domain and
      a second from the other domain. The suggestion of two domains is supported by
      observations that the 24 kDa NapC(sol) cleaves to yield a 12 kDa haem-staining
      band. Determination of the cleavage site showed it was between two equally sized
      di-haem domains predicted from sequence analysis.

PMID- 12186632
TI  - Synthesis and secretion of Muc4/sialomucin complex: implication of intracellular
      proteolysis.
AB  - Muc4/sialomucin complex (SMC) is a heterodimeric glycoprotein complex implicated
      in epithelial protection and overexpressed in some tumours. It is encoded by a
      single gene, and the two subunits are produced by proteolytic cleavage at a time
      before substantial O-glycosylation, near the time of transit from the endoplasmic
      reticulum to the Golgi. Although Muc4/SMC is translated as a membrane protein, it
      is produced as a soluble form in many epithelia. Transfection experiments using
      Cos-7, HBL-100 human epithelial, MCF-7 human breast tumour and HC11 mouse mammary
      cell lines showed that soluble rat Muc4/SMC is produced by a proteolytic cleavage
      mechanism and released by secretion from multiple cell lines, including both
      human and mouse normal epithelial cells and tumour cells. Similar transfection
      experiments demonstrated the same mechanism for the human analogue MUC4. Gel
      electrophoresis analyses of deglycosylated membrane and soluble transmembrane
      subunits and of the membrane-associated cleavage fragment indicated a released
      cleavage product of 25 kDa, resulting from cleavage between two epidermal growth
      factor-like domains. Further evidence for this site was obtained from deletion
      mutants removing this region of the protein, which blocked secretion. Finally,
      pulse-chase analyses of Muc4/SMC biosynthesis indicated no kinetic difference
      between the timing of the cleavage to release the soluble form and that to
      produce the two subunits, indicating that the soluble form is created early in
      transit to the cell surface. These studies provide the first clear evidence that
      membrane mucins can be released from cells by an intracellular proteolytic
      mechanism that leads to secretion of the soluble form of the mucin.

PMID- 12186633
TI  - Cell-surface prion protein interacts with glycosaminoglycans.
AB  - We used ELISA and flow cytometry to study the binding of prion protein PrP to
      glycosaminoglycans (GAGs). We found that recombinant human PrP (rPrP) binds GAGs
      including chondroitin sulphate A, chondroitin sulphate B, hyaluronic acid, and
      heparin. rPrP binding to GAGs occurs via the N-terminus, a region known to bind
      divalent cations. Additionally, rPrP binding to GAGs is enhanced in the presence
      of Cu2+ and Zn2+, but not Ca2+ and Mn2+. rPrP binds heparin strongest, and the
      binding is inhibited by certain heparin analogues, including heparin disaccharide
      and sulphate-containing monosaccharides, but not by acetylated heparin. Full
      length normal cellular prion protein (PrPC), but not N-terminally truncated PrPC
      species, from human brain bind GAGs in a similar Cu2+/Zn2+-enhanced fashion. We
      found that GAGs specifically bind to a synthetic peptide corresponding to amino
      acid residues 23-35 in the N-terminus of rPrP. We further demonstrated that while
      both wild-type PrPC and an octapeptide-repeat-deleted mutant PrP produced by
      transfected cells bound heparin at the cell surface, the PrP N-terminal deletion
      mutant and non-transfectant control failed to bind heparin. Binding of heparin to
      wild-type PrPC on the cell surface results in a reduction of the level of cell
      surface PrPC. These results provide strong evidence that PrPC is a surface
      receptor for GAGs.

PMID- 12186634
TI  - High-resolution physical map for chromosome 16q12.1-q13, the Blau syndrome locus.
AB  - BACKGROUND: The Blau syndrome (MIM 186580), an autosomal dominant granulomatous
      disease, was previously mapped to chromosome 16p12-q21. However, inconsistent
      physical maps of the region and consequently an unknown order of microsatellite
      markers, hampered us from further refining the genetic locus for the Blau
      syndrome. To address this problem, we constructed our own high-resolution
      physical map for the Blau susceptibility region. RESULTS: We generated a high
      resolution physical map that provides more than 90% coverage of a refined Blau
      susceptibility region. The map consists of four contigs of sequence tagged site
      based bacterial artificial chromosomes with a total of 124 bacterial artificial
      chromosomes, and spans approximately 7.5 Mbp; however, three gaps still exist in
      this map with sizes of 425, 530 and 375 kbp, respectively, estimated from
      radiation hybrid mapping. CONCLUSIONS: Our high-resolution map will assist
      genetic studies of loci in the interval from D16S3080, near D16S409, and D16S408
      (16q12.1 to 16q13).

PMID- 12186635
TI  - Conservation of the COP9/signalosome in budding yeast.
AB  - BACKGROUND: The COP9/signalosome (CSN), a multiprotein complex consisting of
      eight subunits, is implicated in a wide variety of regulatory processes including
      cell cycle control, signal transduction, transcriptional activation, and plant
      photomorphogenesis. Some of these functions have been linked to CSN-associated
      enzymes, including kinases and an activity that removes the ubiquitin-like
      protein NEDD8/Rub1p from the cullin subunit of E3 ligases. CSN is highly
      conserved across species from fission yeast to humans, but sequence comparison
      has failed to identify the complex in budding yeast, except for a putative CSN5
      subunit called Rri1p. RESULTS: We show that disruption of four budding yeast
      genes, PCI8 and three previously uncharacterized ORFs, which encode proteins
      interacting with Rrr1p/Csn5p, each results in the accumulation of the cullin
      Cdc53p exclusively in the Rub1p-modified state. This phenotype, which resembles
      that of fission yeast csn mutants, is due to a biochemical defect in
      deneddylation that is complemented by wild-type cell lysate and by purified human
      CSN in vitro. Although three of the four genes encode proteins with PCI domains
      conserved in metazoan CSN proteins, their disruption does not confer the DNA
      damage sensitivity described in some fission yeast csn mutants. CONCLUSIONS: Our
      studies present unexpected evidence for the conservation of a functional
      homologue of the metazoan CSN, which mediates control of cullin neddylation in
      budding yeast.

PMID- 12186637
TI  - Is mass spectrometry ready for proteome-wide protein expression analysis?
AB  - Recent advances in mass spectrometry will soon allow routine analysis of protein
      expression levels. How close are we to true quantitative proteomics?

PMID- 12186638
TI  - The DNA-binding region of RAG 1 is not a homeodomain.
AB  - Functional annotation is used to catalog information that would be of value in
      experimental design and analysis but annotations in public databases are often
      incorrect. Here, one such case is discussed.

PMID- 12186639
TI  - Preferred codons and amino acid couples in hyperthermophiles.
AB  - BACKGROUND: Most organisms grow at temperatures from 20 to 50 degrees C but some
      prokaryotes, including Archaea and Bacteria, are capable of withstanding higher
      temperatures, from 60 to >100 degrees C. What makes these cells so resistant to
      heat? Their biomolecules must be sufficiently stable, especially proteins, to
      work under these extreme conditions, but the bases for thermostability remains
      elusive. RESULTS: The preferential usage of certain couples of amino acids and
      codons in thermal adaptation was investigated, by comparative proteome analysis,
      using 28 complete genomes from 18 mesophiles, 4 thermophiles, and 6
      hyperthermophiles. In the hyperthermophiles proteomes, whenever the percent of
      Glu (E) and Lys (K) Increased, the percent of Gln (Q) and His (H) decreased, so
      that the E+K/Q+H ratio was > 4,5; in the mesophiles proteomes, it was < 2,5 and
      in the thermophiles an intermediary value was observed. The E+K/Q+H ratios for
      chaperonins, potentially thermostable proteins, were higher than their proteome
      ratios whereas, for DNA ligases, not necessarily thermostable, they followed the
      proteome ones. Analysis of codon usage revealed that hyperthermophiles preferred
      AGR codons for Arg in detriment of CGN codons, which were preferred by
      mesophiles. CONCLUSIONS: The results suggested that the E+K/Q+H ratio may provide
      a useful mark for distinguishing hyperthermophilic, thermophilic and mesophilic
      prokaryotes and that the high percent of the amino acid couple E+K, consistently
      associated to the low percent of the pair Q+H, could contribute to protein
      thermostability. Second, the preference for AGR codons for Arg was a signature of
      all hyperthermophilics so far analyzed.

PMID- 12186641
TI  - Comparative genomics comes of age.
AB  - A report on the 2002 annual Cold Spring Harbor Laboratory meeting on Genome
      Sequencing and Biology, Cold Spring Harbor, NY, USA, 7-11 May 2002.

PMID- 12186640
TI  - Comparative biology and genomics join forces to decipher the diversity of life.
AB  - A report on the Cold Spring Harbor Laboratory meeting on the Evolution of
      Developmental Diversity, Cold Spring Harbor, NY, USA, 17-21 April 2002.

PMID- 12186642
TI  - The many layers of immunity.
AB  - A report on the Cologne Spring Meeting 'Immunity', Cologne, Germany, 13-15 March
      2002.

PMID- 12186643
TI  - Back to basics.
AB  - A report on the annual Association of Biomolecular Resource Facilities (ABRF)
      meeting, Austin, Texas, 9-12 March 2002.

PMID- 12186644
TI  - Integromics: challenges in data integration.
AB  - A report on Barnett International's 4th annual Bioinformatics and Data
      Integration conference, Philadelphia, USA, 7-8 March 2002.

PMID- 12186645
TI  - Expression profiling of Drosophila imaginal discs.
AB  - BACKGROUND: In the Drosophila larva, imaginal discs are programmed to produce
      adult structures at metamorphosis. Although their fate is precisely determined,
      these organs remain largely undifferentiated in the larva. To identify genes that
      establish and express the different states of determination in discs and larval
      tissues, we used DNA microarrays to analyze mRNAs isolated from single imaginal
      discs. RESULTS: Linear amplification protocols were used to generate
      hybridization probes for microarray analysis from poly(A)+ RNA from single
      imaginal discs containing between 10,000 and 60,000 cells. Probe reproducibility
      and degree of representation were tested using microarrays with approximately
      6,000 different cDNAs. Hybridizations with probes that had been prepared
      separately from the same starting RNA pool had a correlation coefficient of 0.97.
      Expression-profile comparisons of the left and right wing imaginal discs from the
      same larva correlated with a coefficient of 0.99, indicating a high degree of
      reproducibility of independent amplifications. Using this method, we identified
      genes with preferential expression in the different imaginal discs using pairwise
      comparisons of discs and larval organs. Whereas disc-to-disc comparisons revealed
      only moderate differences, profiles differed substantially between imaginal discs
      and larval tissues, such as larval endodermal midgut and mesodermal fat body.
      CONCLUSIONS: The combination of linear RNA amplification and DNA microarray
      hybridization allowed us to determine the expression profiles of individual
      imaginal discs and larval tissues and to identify genes expressed in tissue
      specific patterns. These methods should be widely applicable to comparisons of
      expression profiles for tissues or parts of tissues that are available only in
      small amounts.

PMID- 12186647
TI  - The dominance of the population by a selected few: power-law behaviour applies to
      a wide variety of genomic properties.
AB  - BACKGROUND: The sequencing of genomes provides us with an inventory of the
      'molecular parts' in nature, such as protein families and folds, and their
      functions in living organisms. Through the analysis of such inventories, it has
      been shown that different genomes have very different usage of parts; for
      example, the common folds in the worm are very different from those in
      Escherichia coli. RESULTS: Despite these differences, we find that the genomic
      occurrence of generalized parts follows a well-known mathematical framework
      called the power law, with a few parts occurring many times and most occurring
      only a few times. This observation is true in a wide variety of genomic contexts.
      Earlier studies found power laws in a few specific cases, such as the occurrence
      of protein families. Here, we find many further cases of power-law behavior, for
      example in the occurrence of pseudogenes and in levels of gene expression. We
      show comprehensively that this behavior applies across many different genomes,
      for many different types of parts (DNA words, InterPro families, protein
      superfamilies and folds, pseudogene families and pseudomotifs), and for the many
      disparate attributes associated with these parts (their functions, interactions
      and expression levels). CONCLUSIONS: Power-law behavior provides a concise
      mathematical description of an important biological feature: the sheer dominance
      of a few members over the overall population. We present this behavior in a
      unified framework and propose that all these observations are connected to an
      underlying DNA duplication process as genomes evolved to their current state.

PMID- 12186646
TI  - The SWIRM domain: a conserved module found in chromosomal proteins points to
      novel chromatin-modifying activities.
AB  - BACKGROUND: Eukaryotic chromosomal components, especially histones, are subject
      to a wide array of covalent modifications and catalytic reorganization. These
      modifications have an important role in the regulation of chromatin structure and
      are mediated by large multisubunit complexes that contain modular proteins with
      several conserved catalytic and noncatalytic adaptor domains. RESULTS: Using
      computational sequence-profile analysis methods, we identified a previously
      uncharacterized, predicted alpha-helical domain of about 85 residues in
      chromosomal proteins such as Swi3p, Rsc8p, Moira and several other
      uncharacterized proteins. This module, termed the SWIRM domain, is predicted to
      mediate specific protein-protein interactions in the assembly of chromatin
      protein complexes. In one group of proteins, which are highly conserved
      throughout the crown-group eukaryotes, the SWIRM domain is linked to a catalytic
      domain related to the monoamine and polyamine oxidases. Another human protein has
      the SWIRM domain linked to a JAB domain that is involved in protein degradation
      through the ubiquitin pathway. CONCLUSIONS: Identification of the SWIRM domain
      could help in directed experimental analysis of specific interactions in
      chromosomal proteins. We predict that the proteins in which it is combined with
      an amino-oxidase domain define a novel class of chromatin-modifying enzymes,
      which are likely to oxidize either the amino group of basic residues in histones
      and other chromosomal proteins or the polyamines in chromatin, and thereby alter
      the charge distribution. Other forms, such as KIAA1915, may link chromatin
      modification to ubiquitin-dependent protein degradation.

PMID- 12186648
TI  - Identification of Schistosoma mansoni gender-associated gene transcripts by cDNA
      microarray profiling.
AB  - BACKGROUND: Parasitic helminths of the genus Schistosoma mate, achieve sexual
      maturity and produce eggs in the bloodstream of their definitive hosts, and the
      most important pathological consequences of the infection are associated with
      this process. We have used cDNA microarray technology to initiate genome-wide
      gene-expression studies of sex and sexual development in mature Schistosoma
      mansoni parasites. RESULTS: An S. mansoni-specific cDNA microarray was fabricated
      using 576 expressed sequence tags selected from three cDNA libraries and
      originating from two different parasite developmental stages. Five independent
      cDNA microarray hybridizations were analyzed using stringent filtering criteria
      and careful quality control, leading to the identification of 12 new female
      associated and 4 new male-associated gene transcripts in the mature adult
      schistosome. Statistical analysis of variation demonstrated high levels of
      agreement within a cDNA microarray (correlation coefficient 0.91; median
      coefficient of variation 11.1%) and between cDNA microarrays (correlation
      coefficient 0.90; median coefficient of variation 14.4%). RT-PCR analysis
      confirmed the cDNA microarray results, thereby supporting the reliability of the
      system. CONCLUSIONS: Our study expands the list of S. mansoni gender-associated
      gene transcripts from all previous studies by a factor of two. Among the new
      associations identified, a tyrosinase ortholog was preferentially expressed in
      the adult female, and a dynein light-chain ortholog was highly induced in the
      adult male. cDNA microarrays offer the potential for exponential leaps in the
      understanding of parasite biology and this study shows how molecules involved in
      sexual biology can be rapidly identified.

PMID- 12186649
TI  - Identification of genes involved in ceramide-dependent neuronal apoptosis using
      cDNA arrays.
AB  - BACKGROUND: Ceramide is important in many cell responses, such as proliferation,
      differentiation, growth arrest and apoptosis. Elevated ceramide levels have been
      shown to induce apoptosis in primary neuronal cultures and neuronally
      differentiated PC 12 cells. RESULTS: To investigate gene expression during
      ceramide-dependent apoptosis, we carried out a global study of gene expression in
      neuronally differentiated PC 12 cells treated with C2-ceramide using an array of
      9,120 cDNA clones. Although the criteria adopted for differential hybridization
      were stringent, modulation of expression of 239 genes was identified during the
      effector phase of C2-ceramide-induced cell death. We have made an attempt at
      classifying these genes on the basis of their putative functions, first with
      respect to known effects of ceramide or ceramide-mediated transduction systems,
      and then with respect to regulation of cell growth and apoptosis. CONCLUSIONS:
      Our cell-culture model has enabled us to establish a profile of gene expression
      during the effector phase of ceramide-mediated cell death. Of the 239 genes that
      met the criteria for differential hybridization, 10 correspond to genes
      previously involved in C2-ceramide or TNF-alpha signaling pathways and 20 in
      neuronal disorders, oncogenesis or more broadly in the regulation of
      proliferation. The remaining 209 genes, with or without known functions,
      constitute a pool of genes potentially implicated in the regulation of neuronal
      cell death.

PMID- 12186650
TI  - Anticipatory evolution and DNA shuffling.
AB  - DNA shuffling has proven to be a powerful technique for the directed evolution of
      proteins. A mix of theoretical and applied research has now provided insights
      into how recombination can be guided to more efficiently generate proteins and
      even organisms with altered functions.

PMID- 12186651
TI  - Transcriptome analysis of the retina.
AB  - The retina offers unique opportunities to define the molecular and cellular
      pathways mediating neuronal function and disease because of its morphological
      complexity, well-defined role in visual transduction and the availability of
      mutants. These investigations are being greatly facilitated by the ongoing
      identification of genes expressed in the retina using high-throughput methods.

PMID- 12186653
TI  - Iron stress in plants.
AB  - Although iron is an essential nutrient for plants, its accumulation within cells
      can be toxic. Plants, therefore, respond to both iron deficiency and iron excess
      by inducing expression of different gene sets. Here, we review recent advances in
      the understanding of iron homeostasis in plants gained through functional genomic
      approaches

PMID- 12186652
TI  - Can mammalian cloning combined with embryonic stem cell technologies be used to
      treat human diseases?
AB  - Cloning is commonly perceived as a means of generating genetically identical
      individuals, but it can also be used to obtain genetically matched embryo-derived
      stem cells, which could potentially be used in the treatment of patients. A
      recent report offers the first 'proof of principle' of such cloning for
      therapeutic purposes, referred to as nuclear transplantation to produce stem
      cells for autologous transplantation.

PMID- 12186654
TI  - Toll-like receptors: a family of pattern-recognition receptors in mammals.
AB  - The innate immune system uses a variety of germline-encoded pattern-recognition
      receptors that recognize conserved microbial structures or pathogen-associated
      molecular patterns, such as those that occur in the bacterial cell-wall
      components peptidoglycan and lipopolysaccharide. Recent studies have highlighted
      the importance of Toll-like receptors (TLRs) as a family of pattern-recognition
      receptors in mammals that can discriminate between chemically diverse classes of
      microbial products. First identified on the basis of sequence similarity with the
      Drosophila protein Toll, TLRs are members of an ancient superfamily of proteins,
      which includes related proteins in invertebrates and plants. TLRs activate innate
      immune defense reactions, such as the release of inflammatory cytokines, but
      increasing evidence supports an additional critical role for TLRs in
      orchestrating the development of adaptive immune responses. The sequence
      similarity between the intracellular domains of the TLRs and the mammalian
      interleukin-1 and interleukin-18 cytokine receptors reflects the use of a common
      intracellular signal-transduction cascade triggered by these receptor classes.
      But more recent findings have demonstrated that there are in fact TLR-specific
      signaling pathways and cellular responses. Thus, TLRs function as sentinels of
      the mammalian immune system that can discriminate between diverse pathogen
      associated molecular patterns and then elicit pathogen-specific cellular immune
      responses.

PMID- 12186655
TI  - BioArray Software Environment (BASE): a platform for comprehensive management and
      analysis of microarray data.
AB  - The microarray technique requires the organization and analysis of vast amounts
      of data. These data include information about the samples hybridized, the
      hybridization images and their extracted data matrices, and information about the
      physical array, the features and reporter molecules. We present a web-based
      customizable bioinformatics solution called BioArray Software Environment (BASE)
      for the management and analysis of all areas of microarray experimentation. All
      software necessary to run a local server is freely available.

PMID- 12186656
TI  - Comparative risk judgements for oral health hazards among Norwegian adults: a
      cross sectional study.
AB  - BACKGROUND: This study identified optimistic biases in health and oral health
      hazards, and explored whether comparative risk judgements for oral health hazards
      vary systematically with socio-economic characteristics and self-reported risk
      experience. METHODS: A simple random sample of 1,190 residents born in 1972 was
      drawn from the population resident in three counties of Norway. A total of 735
      adults (51% women) completed postal questionnaires at home. RESULTS: Mean ratings
      of comparative risk judgements differed significantly (p < 0.001) from the mid
      point of the scales. T-values ranged from -13.1 and -12.1 for the perceived risk
      of being divorced and loosing all teeth to -8.2 and -7.8 (p < 0.001) for having
      gum disease and toothdecay. Multivariate analyses using General Linear Models,
      GLM, revealed gender differences in comparative risk judgements for gum disease,
      whereas social position varied systematically with risk judgements for tooth
      decay, gum disease and air pollution. The odds ratios for being comparatively
      optimistic with respect to having gum disease were 2.9, 1.9, 1.8 and 1.5 if being
      satisfied with dentition, having a favourable view of health situation, and
      having high and low involvement with health enhancing and health detrimental
      behaviour, respectively. CONCLUSION: Optimism in comparative judgements for
      health and oral health hazards was evident in young Norwegian adults. When
      judging their comparative susceptibility for oral health hazards, they consider
      personal health situation and risk behaviour experience.

PMID- 12186657
TI  - A approximately 35 kDa polypeptide from insect cells binds to yeast ACS like
      elements in the presence of ATP.
AB  - BACKGROUND: The S. cerevisiae origin recognition complex binds to the ARS
      consensus sequence in an ATP dependent fashion. Recently, the yeast Cdc6 has been
      reported to have DNA binding activity. Conservation of replication proteins among
      different species strongly supports their functional similarity. Here we report
      the results of an investigation into the DNA binding activity of human Cdc6
      protein. Cdc6 was expressed and purified from baculovirus infected Sf9
      (Spodoptera frugiperda) insect cells as GST fusion protein (GST-Cdc6) and its DNA
      binding activity was tested. RESULTS: Partially purified fractions containing
      GSTCdc6 or GST showed an ACS binding activity in an ATP dependent manner.
      However, further purification revealed the presence of a putative 35 kDa insect
      cell protein (p35) which was found responsible for the DNA binding activity. A
      close match to the 9/11 bases of the ARS consensus sequence was sufficient for
      p35 binding activity. A DNA fragment from the human c-myc origin region
      containing yeast ACS like elements also showed p35 binding activity. CONCLUSIONS:
      We have identified a Spodoptera frugiperda protein with ATP dependent DNA binding
      activity to ACS like elements. ACS like elements have been reported to be
      essential for ORC binding and replication initiation in yeast but their role in
      higher eukaryotes still remains elusive. Like the ARS consensus sequence elements
      of yeast, ACS like elements found in c-myc and lamin beta 2 origin regions may
      play similar roles in replication and indicate a conserved role for this DNA
      motif among eukaryotes.

PMID- 12186658
TI  - Increasing the satisfaction of general practitioners with continuing medical
      education programs: a method for quality improvement through increasing teacher
      learner interaction.
AB  - BACKGROUND: Continuing medical education (CME) for general practitioners relies
      on specialist-based teaching methods in many settings. Formal lectures by
      specialists may not meet the learning needs of practitioners and may cause
      dissatisfaction with traditional CME. Increasing learner involvement in teaching
      programs may improve learner satisfaction. METHODS: A quality improvement program
      for CME for 18 general practitioners in the Tel Aviv region was designed as a
      result of dissatisfaction with traditional CME activities. A two-step strategy
      for change was developed. The CME participants first selected the study topics
      relevant to them from a needs assessment and prepared background material on the
      topics. In the second step, specialist teachers were invited to answer questions
      arising from the preparation of selected topics. Satisfaction with the
      traditional lecture program and the new participatory program were assessed by a
      questionnaire. The quality criteria included the relevance, importance and
      applicability of the CME topic chosen to the participant's practice, the clarity
      of the presentation and the effective use of teaching aids by the lecturer and
      the potential of the lecturer to serve as a consultant to the participant.
      RESULTS: The participatory model of CME significantly increased satisfaction with
      relevance, applicability and interest in CME topics compared to the traditional
      lecture format. CONCLUSIONS: Increased learner participation in the selection and
      preparation of CME topics, and increased interaction between CME teachers and
      learners results in increased satisfaction with teaching programs. Future study
      of the effect of this model on physician performance is required.

PMID- 12186659
TI  - Non-home prepared foods: contribution to energy and nutrient intake of consumers
      living in two low-income areas in Nairobi.
AB  - OBJECTIVE: : To determine the nutritional importance of non-home prepared foods
      for men, women and schoolchildren living in two low-income residential areas of
      Nairobi, and the sources of these non-home prepared foods. DESIGN, SETTING AND
      SUBJECTS: : A survey was conducted in Korogocho, a slum area, and Dandora, a low
      middle-income residential area. Some 241 men, 254 women and 146 children aged 9
      to 14 years were included in the study. Food intake was measured using three 24
      hour recalls per individual, with special attention on the sources of all foods
      consumed. RESULTS: : The median proportion of daily energy intake of consumers
      provided by non-home prepared foods ranged from 13% for schoolchildren in
      Korogocho to 36% for men in Dandora. The median contribution to fat intake was
      higher than to energy, but the contributions to iron and vitamin A intakes were
      lower than to energy intake. Men consumed more non-home prepared foods on
      weekdays than at the weekend. Intakes of energy and most nutrients were below
      Kenyan Recommended Daily Intakes in all groups, but similar for consumers and non
      consumers. In Korogocho, street foods were the main source of non-home prepared
      foods. In Dandora, both kiosks and street foods were major sources. CONCLUSIONS:
      : Non-home prepared foods are an important source of energy and nutrients for
      men, women and schoolchildren in Nairobi. In Korogocho, street foods, and in
      Dandora, both kiosks and street foods are the main sources of non-home prepared
      foods. The adequacy of energy and nutrient intakes does not differ between
      consumers and non-consumers of non-home prepared foods.

PMID- 12186660
TI  - Underreporting of energy intake is less common among pregnant women in Indonesia.
AB  - OBJECTIVES: To evaluate the ratio of reported energy intake to basal metabolic
      rate (EI/BMR) among pregnant Indonesian women, as well as identifying risk
      factors for being an underreporter. DESIGN: Longitudinal study of dietary intake,
      using six repeated 24-hour diet recalls each trimester. Basal metabolic rate was
      estimated from body weight and physical activity from occupation. The lower 95%
      confidence interval for plausible EI/BMR was calculated and the proportion of
      underreporters estimated. Risk factors for being an underreporter were assessed
      in multivariate logistic regression analyses. SETTING: Purworejo District,
      central Java, Indonesia. SUBJECTS: Pregnant women RESULTS: For the three
      trimesters, EI/BMR ratio was and (mean+/-standard deviation), respectively. The
      proportion of underreporters was 29.7%, 16.2% and 17.6%. Characteristics
      significantly associated with underreporting in at least one trimester included
      high body mass index and low education. CONCLUSIONS: Levels of underreporting
      were low among the pregnant Indonesian women during the second and third
      trimesters. The low EI/BMR ratio during the first trimester likely reflects a
      true low intake due to nausea, rather than underreporting. Risk factors for being
      an underreporter included those known from developed countries, i.e. obesity and
      low education.

PMID- 12186661
TI  - Nutrition interventions by primary care staff: a survey of involvement, knowledge
      and attitude.
AB  - OBJECTIVE: To undertake a survey to investigate the quality and format of
      nutrition health promotion in UK primary care. Data from both primary care
      practitioners - i.e. level of nutritional knowledge and attitude towards
      nutrition interventions - and patients - i.e. the format and quality of dietary
      consultations - are presented. DESIGN: A self-completion questionnaire was used
      to assess nutritional knowledge and attitude of primary care staff towards
      nutrition interventions. Data regarding the format and quality of the dietary
      consultation were collected from patients using a screening question and follow
      up questionnaire. SETTING: Twelve general practices in a city in north-east
      England. SUBJECTS: One hundred and nine primary care staff, and 2400 consecutive
      patients recruited from the 12 practices. RESULTS: Seventy-seven per cent of
      primary care staff completed the questionnaire. Sixty-five per cent of the
      knowledge questions were answered correctly by most practitioners. Questions
      containing complex nutritional terminology were answered poorly. Most
      practitioners believed primary care teams have an essential role in giving
      dietary advice. Thirteen per cent of patients reported that they had discussed
      diet. Of these, 40% were asked to make dietary changes; 20% discussed how they
      cooked or prepared food; and 33% were asked to make a follow-up appointment.
      CONCLUSION: Encouraging signs included good levels of nutritional knowledge and
      belief amongst staff that they should be involved in nutrition interventions.
      Patients reported that they understood and felt able to achieve the dietary
      changes suggested. Less encouraging were little evidence of discussion about the
      practical aspects of food and fairly low rates of follow-up being arranged.

PMID- 12186662
TI  - Relative bias in diet history measurements: a quality control technique for
      dietary intervention trials.
AB  - OBJECTIVE: Investigation of relative bias in diet history measurement during
      dietary intervention trials. DESIGN: Retrospective analysis of human dietary data
      from two randomised controlled trials examining modified fat diets in the
      prevention and treatment of type II diabetes mellitus. SETTING: Wollongong,
      Australia. SUBJECTS: Thirty-five overweight, otherwise healthy subjects in trial
      1 and 56 subjects with diabetes in trial 2. INTERVENTIONS: Diet history
      interviews and three-day weighed food records administered at one-month intervals
      in trial 1 and three-month intervals in trial 2. RESULTS: In a cross-sectional
      bias analysis, graphs of the association between bias and mean dietary intake
      showed that bias decreased in higher carbohydrate consumers in trial 1 (r = 
      0.344, P < 0.05). No other significant associations were found. In a longitudinal
      analysis, bias did not change over time in either trial. There were no
      significant differences in bias magnitudes between the trials, with the exception
      of monounsaturated fat measurement where bias was significantly greater and more
      positive in trial 2, indicating overestimation of monounsaturated fat intake with
      the diet history. Subjects in control and intervention groups underestimated
      energy, fat, saturated fat and alcohol intakes with the diet history in both
      trials. Overweight and obese individuals appeared to make the greatest
      contribution to the overall underestimation of saturated fat intake by the diet
      history regardless of whether they were in the control or intervention group and
      whether they were healthy or had diabetes. CONCLUSION: Bias in diet history
      measurement appears to be macronutrient-specific, with energy, fat and saturated
      fat consistently underreported in the interview by subjects with and without
      diabetes and in both intervention and control groups in a dietary intervention
      trial. Relative bias analysis appears to be an informative tool in quality
      control for dietary intervention trials when biochemical markers are unavailable.

PMID- 12186663
TI  - Assessment of breast-feeding promotion in hospitals and follow-up survey of
      mother-infant pairs in Germany: the SuSe Study.
AB  - OBJECTIVE: To assess breast-feeding promotion in maternity hospitals and breast
      feeding prevalences during the first year of life in mother-infant pairs in
      Germany. DESIGN: Cross-sectional assessment of breast-feeding practices in a
      random sample of German maternity hospitals by use of a postal questionnaire.
      Follow-up of mother-infant pairs recruited in the participating hospitals to
      assess breast-feeding prevalences and infant feeding practices by use of a
      telephone interview 14 days after birth and food-frequency questionnaires mailed
      at the end of the 2nd, 4th, 6th, 9th and 12th month of life. Use of indicators
      for breast-feeding proposed by the World Health Organization (WHO) and the United
      Nations Children's Fund (UNICEF). SETTING: Nation-wide survey. SUBJECTS: One
      hundred and seventy-seven maternity hospitals, 1717 mother-infant pairs. RESULTS:
      There were wide variations in breast-feeding promotion in hospitals as evaluated
      by the practice of the '10 Steps to Successful Breastfeeding' given by WHO and
      UNICEF for certification as a 'Babyfriendly Hospital'. Some steps (3, 4, 8) were
      practised in about 90% of the hospitals, others (steps 7, 9) in only 10%.
      Prevalences for exclusive (total) breast-feeding as defined by WHO were: 73%
      (86%) at discharge, 60% (85%) at 14 days, 42% (70%) at 2 months, 33% (59%) at 4
      months, 10% (48%) at 6 months, <1% (26%) at 9 months and 0 (13%) at 12 months.
      CONCLUSIONS: By use of indicators proposed by WHO and UNICEF, a differentiated
      insight into the breast-feeding situation in Germany has become possible.
      Moderate levels of breast-feeding promotion in hospitals resulted in almost
      satisfactory early breast-feeding prevalences but were not effective for long
      term breast-feeding success in most mothers.

PMID- 12186664
TI  - The relationship between frequency of carbohydrates intake and dental caries: a
      cross-sectional study in Italian teenagers.
AB  - OBJECTIVE: To propose an approach for investigation of the relationship between
      the frequency of carbohydrates intake and dental caries in real-life conditions.
      DESIGN: The frequency of separate eating events (with the exclusion of lunch and
      dinner) and their sugars and starch content were assessed on the basis of diaries
      collected for seven consecutive days. The total number of decayed, missing and
      filled teeth (DMFT) was assessed through clinical examination. The interrelation
      between DMFT and frequency of eating events was analysed through Pearson
      correlation coefficient and stepwise forward linear regression analysis. SETTING:
      Italy. SUBJECTS: One hundred and ninety-three students (males and females, mean
      age 16 years) of a secondary school. RESULTS: Individual DMFT varied between 0
      (24% of subjects) and 12, with a mean of 3. Once lunch and dinner were excluded,
      the mean number of separate eating events was 2.9. A statistically significant
      relationship was found between DMFT and eating frequency thus defined.
      Correlations were calculated considering only eating events containing a
      proportion of sugars or starch higher than different cut-off levels. In a
      stepwise multiple regression model for DMFT, the frequency of 'high sugars and
      high starch events' accounted for 8% of the DMFT variance. Overall frequency of
      separate eating events defined according to their content of both sugars and
      starch accounted for 18% of the DMFT variance. A stronger correlation was found
      among males only. CONCLUSIONS: The precise characterisation of eating events in
      terms of their sugars and starch content allows us to explain a consistent
      percentage of the variability in DMFT.

PMID- 12186665
TI  - Validity of self-reported height and weight in 4808 EPIC-Oxford participants.
AB  - OBJECTIVE: To assess the validity of self-reported height and weight by
      comparison with measured height and weight in a sample of middle-aged men and
      women, and to determine the extent of misclassification of body mass index (BMI)
      arising from differences between self-reported and measured values. DESIGN:
      Analysis of self-reported and measured height and weight data from participants
      in the Oxford cohort of the European Prospective Investigation into Cancer and
      Nutrition (EPIC-Oxford). SUBJECTS: Four thousand eight hundred and eight British
      men and women aged 35-76 years. RESULTS: Spearman rank correlations between self
      reported and measured height, weight and BMI were high (r > 0.9, P < 0.0001).
      Height was overestimated by a mean of 1.23 (95% confidence interval (CI) 1.11
      1.34) cm in men and 0.60 (0.51-0.70) cm in women; the extent of overestimation
      was greater in older men and women, shorter men and heavier women. Weight was
      underestimated by a mean of 1.85 (1.72-1.99) kg in men and 1.40 (1.31-1.49) kg in
      women; the extent of underestimation was greater in heavier men and women, but
      did not vary with age or height. Using standard categories of BMI, 22.4% of men
      and 18.0% of women were classified incorrectly based on self-reported height and
      weight. After correcting the self-reported values using predictive equations
      derived from a 10% sample of subjects, misclassification decreased to 15.2% in
      men and 13.8% in women. CONCLUSIONS: Self-reported height and weight data are
      valid for identifying relationships in epidemiological studies. In analyses where
      anthropometric factors are the primary variables of interest, measurements in a
      representative sample of the study population can be used to improve the accuracy
      of estimates of height, weight and BMI.

PMID- 12186666
TI  - Development, validation and utilisation of food-frequency questionnaires - a
      review.
AB  - OBJECTIVE: The purpose of this review is to provide guidance on the development,
      validation and use of food-frequency questionnaires (FFQs) for different study
      designs. It does not include any recommendations about the most appropriate
      method for dietary assessment (e.g. food-frequency questionnaire versus weighed
      record). METHODS: A comprehensive search of electronic databases was carried out
      for publications from 1980 to 1999. Findings from the review were then commented
      upon and added to by a group of international experts. RESULTS: Recommendations
      have been developed to aid in the design, validation and use of FFQs. Specific
      details of each of these areas are discussed in the text. CONCLUSIONS: FFQs are
      being used in a variety of ways and different study designs. There is no gold
      standard for directly assessing the validity of FFQs. Nevertheless, the outcome
      of this review should help those wishing to develop or adapt an FFQ to validate
      it for its intended use.

PMID- 12186668
TI  - A review of the MAFF Optimal Nutrition Status research programme: folate, iron
      and copper.
AB  - OBJECTIVE: The objective was to conduct a critical appraisal of research
      conducted within one of the UK government's research programmes, Optimal
      Nutrition Status, and to place the findings of this work in the context of the
      international research effort, to assist policy makers and advisers. Nine
      nutrients are addressed within the programme; the findings for three of these are
      reported here: folate/folic acid, iron and copper. DESIGN: To conduct the review,
      the researchers had access to all unpublished progress reports, submitted to
      officials, arising from the projects. The overall assessment criterion was
      whether the information generated by the research programme could be regarded as
      reliable experimental data of direct relevance to setting optimal dietary
      requirements for the particular micronutrients. However, findings were also
      assessed against specific scientific criteria concerning understanding of the
      bioavailability, interactions, development of functional markers and inter
      individual variations in metabolism, for each of the nutrients scrutinised.
      RESULTS: The results of the review indicated that many important questions are
      indeed being addressed by the UK government's research programme, and that the
      work is contributing to the overall research effort being conducted world-wide on
      this important subject. CONCLUSIONS: Many major questions still need to be
      addressed before it will be possible to identify optimal intakes for various sub
      populations. These priorities are summarised in the paper.

PMID- 12186667
TI  - A comparison of five questionnaires to assess alcohol consumption in a
      Mediterranean population.
AB  - OBJECTIVE: To evaluate the reliability of alcohol consumption measured by five
      different dietary methods in the Catalan Nutrition Survey (1992-1993). DESIGN:
      The different questionnaires used were: (1) two 7-day food records, (2) five
      items addressing alcoholic beverages in a 76-item food-frequency questionnaire,
      (3) a 1-week recall of 13 alcoholic beverages, (4) a 13-item alcoholic beverages
      frequency questionnaire and (5) two 24-hour recalls. SUBJECTS: Ninety-three of
      the 120 adults (aged 20 to 70 years) initially recruited completed the
      questionnaires and provided a peripheral blood sample. RESULTS: Mean daily
      alcohol intakes as assessed by the questionnaires were very similar. Beer was the
      alcoholic beverage most frequently consumed, followed by wine and liquor. Eighty
      two per cent of the study population consumed less than 20 g of alcohol per day.
      No biochemical parameters were significantly correlated with alcohol intake
      estimated from the questionnaires. CONCLUSIONS: We found a satisfactory level of
      reproducibility and validity in the pattern of alcohol consumption across
      different levels and types of alcoholic beverage intake. We also found that the
      self-administered 13-item questionnaire and the 1-week recall were the best
      techniques to measure moderate or low alcohol consumption, suggesting that the
      two methods are the most suitable to assess overall alcohol intake in the general
      population.

PMID- 12186669
TI  - Rifaximin: a new approach to the treatment of travelers' diarrhea. Introduction.

PMID- 12186670
TI  - Epidemiology of travelers' diarrhea.

PMID- 12186671
TI  - Treatment of travelers' diarrhea.

PMID- 12186672
TI  - Rifaximin: a nonabsorbed antimicrobial as a new tool for treatment of travelers'
      diarrhea.

PMID- 12186673
TI  - Rifaximin: a new approach to the treatment of travelers' diarrhea. Conclusion.

PMID- 12186674
TI  - Preventing malaria in international travelers. Introduction.

PMID- 12186675
TI  - Reemergence of malaria: increasing risks for travelers.

PMID- 12186676
TI  - Current drugs for antimalarial chemoprophylaxis: a review of efficacy and safety.

PMID- 12186677
TI  - Expert recommendations for antimalarial prophylaxis.

PMID- 12186679
TI  - Can the behaviour abnormalities induced by gestational stress in rats be
      prevented or reversed?
AB  - Gestational stress increases circulating maternal hormones that produce changes
      in behaviour and impair the feedback regulation of the hypothalamic pituitary
      adrenal axis of the offspring. Prenatally-stressed (PS) rats also release more
      corticotropin-releasing hormone (CRH) in the limbic system in response to
      stimulation than controls. This contributes to their exaggerated fear of
      intimidating situations and depressive-like behaviour. By using different
      treatments given to the pregnant mother, to neonatal or adult offspring, it has
      been possible to learn more about the mechanisms underlying the behavioural
      abnormalities induced by gestational stress. Many of these treatments were also
      able to prevent or reverse the abnormalities. They included maternal
      adrenalectomy and replacement of her basal hormone levels to avoid the prolonged
      elevation of plasma corticosterone, administration of anti-anxiety agents to
      reduce her reactions to the stress and continuous blockade of opioid receptors to
      prevent down-regulation of the foetal opioid system and subsequent alterations in
      behaviour. Hyperanxiety in the adult PS offspring could also be avoided if, as
      neonates, they were handled daily for 10 days, or given an antidepressant,
      amitriptyline for 4-5 weeks in the prepubertal period. Increased fear of novelty
      in adult PS rats could also be abolished by the intracerebro-ventricular
      administration of a CRH antagonist. This suggests that the new non-peptide CRH1
      receptor antagonists that enter the brain might provide an effective treatment
      for the behaviour abnormalities in the offspring arising as a result of
      gestational stress.

PMID- 12186680
TI  - Hypothalamo-pituitary-adrenocortical axis function and hedonic behavior in adult
      male and female rats prenatally stressed by maternal food restriction.
AB  - Neuroendocrine activation during stress is affected by many factors contributing
      to the variability of the stress response. The present study was aimed at
      evaluating long-term changes in hypothalamo-pituitary-adrenocortical (HPA) axis
      function and in hedonic behavior in adult offspring prenatally stressed by
      maternal food restriction, with attention on possible gender differences. Adult
      offspring were blood sampled via a tail artery cannula. Prenatally stressed
      females had significantly higher adrenal weights compared to males. Plasma ACTH
      levels, which rose in response to acute stress induced by handling, were
      significantly higher in females compared to those in males. A similar pattern was
      found in plasma corticosterone. The rise in ACTH levels was more pronounced in
      prenatally stressed rats though the rise in corticosterone failed to be modified.
      Corticotropin releasing hormone (CRH) and proopiomelanocortin mRNA levels in the
      hypothalamic paraventricular nucleus and anterior pituitary, respectively, were
      found to be unchanged. The present experiments failed to reveal a decrease in
      hedonic behavior in prenatally stressed rats. In contrast, in male offspring a
      tendency to a higher sucrose preference was observed. These data together with
      observed changes in hormone and CRH mRNA levels indicate that the gestational
      stress used did not result in a depression-like state in adult offspring.

PMID- 12186681
TI  - Cerebrospinal fluid concentrations of biogenic amines and corticotropin-releasing
      factor in adolescent non-human primates as a function of the timing of adverse
      early rearing.
AB  - Adolescent bonnet macaques nursed as infants by mothers facing unpredictable
      requirements for food procurement (variable foraging demand, VFD) display
      persistent neurobiological disturbances. This study examined the long-term
      neurochemical and behavioral effects of adverse rearing initiated later in
      infancy than in previous cohorts of subjects to test the hypothesis that the
      timing of an early adverse experience would influence patterns of biobehavioral
      outcome. Cisternal cerebrospinal fluid (CSF) monoamine and corticotropin
      releasing factor (CRF) concentrations were obtained from 20 bonnet macaques (11
      VFD-reared and 9 normally reared controls) approximately 2 years after the end of
      differential rearing. VFD-reared primates displayed on multiple samplings
      significantly lower CSF CRF concentrations and higher CSF 5-hydroxyindoleacetic
      acid (5-HIAA) concentration compared to controls. In the VFD-reared, significant
      inverse correlations between CRF and all three monoamines were found (5-HIAA, 3
      methoxy-4-hydroxyphenethyleneglycol and homovanillic acid), most prominently for
      5-HIAA. In controls, but not VFD-reared subjects, CSF CRF was positively
      correlated with changes in "gregariousness" upon presentation of a fear stimulus.
      VFD-reared subjects displayed greater baseline hierarchical engagement than
      controls. In contrast to prior findings, in which rearing under VFD conditions at
      an earlier age led to increased CSF CRF compared with controls, CSF CRF was lower
      after later exposure to VFD rearing than in controls. Thus, the timing of
      exposure to VFD conditions early in life evidently determines whether CSF CRF was
      found to be elevated or decreased, within the context of increased serotonin
      metabolism, during the course of primate maturation.

PMID- 12186682
TI  - Lactation and stress: protective effects of breast-feeding in humans.
AB  - Whilst most research on breast-feeding has been designed to assess its importance
      for infant health or to find a human nutrient replacement for infant formula, the
      effects of breast-feeding on maternal health have received little scientific
      attention. In several animal studies lactation has been shown to be associated
      with a marked blunting of physiological and behavioral responses to physical and
      psychological stress. However, the literature on the effects of lactation on
      stress in humans remains limited. This review focuses primarily on recent
      findings on the effects of breast-feeding on neuroendocrine and behavioral
      responses to acute stress exposure in lactating women. The available data suggest
      that breast-feeding suppresses the hypothalamic-pituitary-adrenal (HPA) axis
      response to physical and psychosocial stress. However, lactation in women, in
      contrast to lactating rats, does not seem to result in a general restraint of the
      endocrine stress response during the whole period of lactation. Recent data
      strongly suggest that the blunted HPA axis response to stress in women seems to
      be counterbalanced if the acute stressor, at least when of a psychosocial nature,
      occurs later than 1 h after suckling. Further elucidation of the underlying
      psychobiological mechanisms involved in suppressed stress responses during
      lactation will no doubt lead to new insights into improved health sequelae of
      breast-feeding in women and to a better understanding of the psychobiology of
      human stress protection in general.

PMID- 12186683
TI  - Sex differences in chronic stress effects on memory in rats.
AB  - Recent studies in rodent models and in humans have shown that the status of both
      the gonadal and adrenal axes (hypothalamic-pituitary-gonadal, HPG and
      hypothalamic-pituitary-adrenal, HPA, respectively) can influence learning and
      memory function. In this article, the effects of activating the HPA axis (stress)
      on performance of memory tasks in rats are reviewed. More importantly, results
      are presented which show that chronic stress has a different impact on
      performance of these tasks depending upon the sex of the rat. These observations
      are novel and potentially important since few studies, animal or human, have
      utilized females as subjects in studies of the stress response. Sex differences
      in the effects of chronic stress on memory were investigated in rats using an
      object recognition task and two spatial memory tasks, radial arm maze and object
      location. Given the same chronic stress--21 days of restraint for 6 h each day-
      males were impaired in all of the memory tests while females showed enhanced
      performance of the spatial memory tasks and no changes in object recognition
      performance. Levels of neurotransmitters and metabolites were measured in brain
      areas important for cognition in the subjects in order to determine neural
      systems that may respond to stress and mediate the cognitive responses. These
      results show that responses of monoamine and amino acid containing neural systems
      may contribute to or underlie sex differences in stress effects on cognition.
      Stress decreased dopaminergic activity in the frontal cortex and amygdala of
      males but not females; whereas, in CA3 of the hippocampus, stress increased
      levels of 5-HT and norepinephrine in females, but not males, and increased GABA
      in males, but not females. Finally, a possible role for estradiol in mediating
      sexually differentiated responses to stress was examined. Behavioral and
      neurochemical evaluations in ovariectomized, stressed females, with or without
      estrogen replacement, suggest that sex differences in response to stress are
      influenced by both the organizing and activating effects of estradiol. A few,
      recent studies in humans, that show sexually dimorphic relationships between
      chronic stress and cognition, are also highlighted. These results in humans are
      consistent with the pattern of results in rats. Clearly, further studies are
      necessary to substantiate sex differences in stress effects on memory function in
      humans and to understand mechanisms whereby estrogen may influence the stress
      response in rats. Nonetheless, recent studies show sexually differentiated
      cognitive responses to chronic stress and underline the importance of considering
      the sex/gender of subjects when studying the stress response.

PMID- 12186684
TI  - Effects of repetitive hypoglycemia on neuroendocrine response and brain tyrosine
      hydroxylase activity in the rat.
AB  - Hypoglycemia-associated autonomic failure (HAAF) is a syndrome of acute
      adaptation to a metabolic stressor, in which neuroendocrine responses to
      repetitive hypoglycemic bouts are blunted. The CNS mechanisms that contribute to
      HAAF are unknown. In the present study, we modeled HAAF in the rat and measured
      the activity of tyrosine hydroxylase (TH) as an index of acute noradrenergic
      activation, to test the hypothesis that noradrenergic activation of the
      hypothalamus might be impaired. In association with a significant counter
      regulatory response to a single bout of hypoglycemia (elevated corticosterone,
      catecholamines, and glucagon), TH activity was elevated overall in brainstem NE
      cell body areas and hypothalamus. With multiple hypoglycemic episodes in a 24 h
      period, the counter-regulatory response was blunted, and hypothalamic TH activity
      was comparable to that of saline-infused controls. In a similar paradigm,
      multiple bouts of CNS neuroglucopenia did not blunt the hyperglycemic or
      corticosterone responses, and were required for elevation of TH activity. This
      alternate response pattern suggests that insulin-induced hypoglycemia and
      cerebral neuroglucopenia represent somewhat different metabolic stressors at the
      CNS.

PMID- 12186685
TI  - Effect of atropine or atenolol on cardiovascular responses to novelty stress in
      freely-moving rats.
AB  - Cardiac hemodynamic mechanisms involved in cardiovascular responses to stress
      were studied in conscious, freely-moving female spontaneously hypertensive rats
      exposed for 15 min to an open-field. When pretreated with saline, the rats
      displayed a rapid rise in blood pressure, heart rate, aortic dP/dt and locomotor
      activity. In rats pretreated with 0.5 mg/kg of methylatropine, the tachycardia
      was slightly, but significantly reduced. In rats pretreated with 1 mg/kg of
      atenolol, the tachycardis and rise in dP/dt were markedly reduced. These data
      suggest that the cardiac responses to stress include predominantly cardiac
      sympathetic activation and a minor component of vagal withdrawal.

PMID- 12186687
TI  - Stress and reproduction: central mechanisms and sex differences in non-rodent
      species.
AB  - Despite extensive research, the mechanisms by which stress affects reproduction
      are unknown. Activation of stress systems could potentially influence
      reproduction at any level of the hypothalamo-pituitary gonadal axis. Nonetheless,
      the predominant impact is on the secretion of gonadotrophin releasing hormone
      (GnRH) from the brain and the secretion of the gonadotrophins, luteinizing
      hormone (LH) and follicle stimulating hormone (FSH), from the gonadotrophs of the
      anterior pituitary gland. When stress is prolonged, it is likely that secretion
      of the gonadotrophins will be suppressed but the effects of acute stress or
      repeated acute stress are not clear. Different stressors activate different
      pathways for varying durations, and the actions of stress vary with sex and are
      influenced by the predominance of particular sex steroids in the circulation. The
      mechanisms by which stress influences reproduction are likely to involve complex
      interactions between a number of central and peripheral pathways and may be
      different in males and females. To understand these mechanisms, it is important
      to determine the stress pathways that are activated by particular stressors and
      to establish how these pathways affect the secretion and actions of GnRH.
      Furthermore, there is a need to know how stress influences the feedback actions
      of gonadal steroids and inhibin.

PMID- 12186688
TI  - Mechanisms for ovarian cycle disruption by immune/inflammatory stress.
AB  - This review summarizes highlights of our experiments investigating mechanisms,
      mediators and sites by which endotoxin disrupts reproductive neuroendocrine
      activity and interferes with the estrous cycle of sheep. Endotoxin, or
      lipopolysaccharide (LPS), is a commonly used model for immune and inflammatory
      stress. When administered to ovary-intact ewes, endotoxin interrupts the
      follicular phase of the cycle by interfering with several steps in the
      preovulatory chain of endocrine events. One such step is the development of high
      frequency LH pulses, which provide an essential stimulus for the preovulatory
      increase in estradiol secretion from the ovarian follicle. Follow-up experiments
      in ovariectomized ewes demonstrate that endotoxin inhibits pulsatile LH secretion
      at both the hypothalamic and pituitary levels, suppressing pulsatile GnRH
      secretion and reducing pituitary responsiveness to GnRH. This disruption of GnRH
      and LH pulsatility is mediated by pathways that include the synthesis of
      prostaglandins and cortisol, both of which are increased by endotoxin. It is
      postulated that a prostaglandin-mediated pathway disrupts the cycle during immune
      and inflammatory stress, whereas a separate cortisol-mediated pathway reinforces
      this disruption and also participates more generally in suppressing cyclicity
      during other stressful situations that activate the hypothalamo-pituitary-adrenal
      axis.

PMID- 12186689
TI  - Hypoglycemia-induced suppression of luteinizing hormone (LH) secretion in intact
      female rhesus macaques: role of vasopressin and endogenous opioids.
AB  - The first objective of this study was to determine whether insulin-induced
      hypoglycemia (IIH) inhibits LH secretion in unrestrained female macaques during
      the follicular phase of the menstrual cycle. There was a consistent inhibitory
      effect of hypoglycemia on LH secretion within 3 h in these females. This
      inhibition was likely an indirect effect since low glucose levels did not inhibit
      GnRH secretion from GT1-1 neurones in vitro. We next investigated whether
      administration of a vasopressin antagonist (AVPa) either alone, or with naloxone
      could reverse the IIH-induced inhibition of LH release. Females were studied in
      the follicular phase during 10 h periods with blood samples collected every 10
      min. Experimental groups were IIH (n=6), IIH+AVPa (n=5) and IIH+AVPa+naloxone
      (n=4). The first 5 h of each study served as a control and hypoglycemia was then
      induced with insulin. The AVPa was given as a bolus (180 microg) just before the
      insulin and was followed by a continuous infusion (180 microg/h) for 5 h.
      Naloxone (5 mg/kg) was given with the AVPa and followed by a continuous infusion
      (5 mg/kg/h) for 5 h. In the IIH group, LH reached its lowest value 3-4 h after
      insulin. Neither AVPa nor AVPa+naloxone infusion reversed the inhibitory action
      of hypoglycemia on LH release. These data suggest that if there are inhibitory
      actions of vasopressin and endogenous opioids on GnRH release induced by
      hypoglycemia, they are not sufficient to explain the suppression of GnRH/LH
      release in intact female primates.

PMID- 12186690
TI  - c-fos mRNA induction in acute and chronic audiogenic stress: possible role of the
      orbitofrontal cortex in habituation.
AB  - To study putative brain circuits involved in habituation to stress, rats were
      exposed daily (30 min for 15 days) to an environment in the presence (Chronic) or
      absence (Acute) of loud noise (105 dB sound pressure level--SPL A Scale).
      Behavioral and endocrine measures of stress were taken throughout this
      habituation period, and both measures displayed strong habituation in the Chronic
      group. All rats were killed immediately after the day 16 exposure, constituting
      an acute stressor for the Acute group, and regional brain activity was assessed
      using c-fos mRNA induction with in situ hybridization. Hearing damage could not
      easily explain these results because additional rats exposed to a similar stress
      protocol exhibited no changes in auditory brainstem evoked potentials. c-fos mRNA
      induction in the central auditory system was similar between the Acute and
      Chronic groups, particularly at lower auditory processing levels, also arguing
      against a simple reduction in auditory processing in the chronically stressed
      rats. However, c-fos mRNA expression was reduced in chronically, as compared to
      acutely, stressed rats in several regions previously implicated in audiogenic
      stress (lateral septum, bed nucleus of the stria terminalis, some preoptic areas,
      and the paraventricular hypothalamic nucleus). Interestingly, the orbitofrontal
      cortex was the only region displaying higher c-fos mRNA induction in the
      chronically as compared to acutely stressed rats. This region has connections to
      several stress-responsive areas and may thus be a critical region actively
      inhibiting stress.

PMID- 12186691
TI  - Suppression of restraint-induced plasma cytokines in mice pretreated with LPS.
AB  - A previous exposure to an inflammatory reaction is known to increase or decrease
      the activation of the hypothalamic-pituitary-adrenal (HPA) axis induced by a
      psychological/physical stress. Beside HPA activation, the non- specific responses
      to these two kinds of stresses involve the immune system including the production
      of cytokines. Therefore, they could interfere in cytokine production. In order to
      test this hypothesis, female C3H mice were first injected i.p. with 5 microg of
      lipopolysaccharide (LPS) or not (C). Eight days later, half of them were
      submitted to a 4 h-restraint (R) applied during the nocturnal part of the dark
      light cycle and sacrificed immediately after (groups LPS-R and C-R), while the
      non restrained mice stayed in their home cages (groups LPS-C and C-C). Restraint
      induced an increase in corticosterone production that was not altered by the
      previous administration of LPS. It had no effect on mitogen-induced
      lymphoproliferation. However, restraint induced an augmentation of plasma
      concentrations of interleukin (IL)-1 and IL-6 that was not observed in animals
      previously exposed to LPS. These results show that restraint, which represents a
      psychological stress is able to induce the production of plasma cytokines in
      mice. They also suggest that LPS may induce a long lasting suppression of plasma
      cytokines through mechanisms that remain to be elucidated.

PMID- 12186692
TI  - Postnatal handling induces long-term modifications in central beta-noradrenergic
      signalling in rats.
AB  - Neonatal handling has been shown to induce a short-term reduction in the binding
      properties of beta-adrenoceptors and in their primary biochemical responses in
      the young rat brain, which may account for the reduced responsiveness to stress
      observed in the handled rats. We have studied the persistence and duration of
      these changes in cerebral cortex, cerebellum and hippocampus at successive stages
      of life in neonatally handled rats. Binding properties of the beta-adrenoceptors
      in handled animals were essentially similar to those of the control rats from 3
      to 24 months of age. However, handling disturbed the efficacy of the beta
      adrenoceptor intracellular signalling since the isoprenaline-induced accumulation
      of cyclic AMP was reduced in cerebral cortex at 1, 12 and 24 months; in
      cerebellum at 12 and 18 months; and in hippocampus at 3 and 12 months. This
      effect might be partially dependent on a regulatory action of handling on the
      adenylyl cyclase enzyme itself since both basal and forskolin-induced
      accumulation of cyclic AMP were persistently reduced. Therefore, postnatal
      handling can be considered as an effective intervention that modifies sensitivity
      to various hormonal and neurochemical signals; these changes may be involved over
      a long period of time in protection against an excessive response to stress.
      These results suggest that the long-lasting adaptation of the adenylyl cyclase
      transduction system, which affects the primary biochemical response of the beta
      adrenoceptor, may participate in the effects of this manipulation.

PMID- 12186693
TI  - A review of the impact of hypnosis, relaxation, guided imagery and individual
      differences on aspects of immunity and health.
AB  - This review considers psychological interventions involving relaxation and guided
      imagery targeting immune functions. The review provides evidence of immune
      control accompanied by reports of enhanced mood and well-being. Three recent
      investigations of the author and his colleagues with self-hypnosis training
      incorporating imagery of the immune system are outlined. In two studies, hypnosis
      buffered the effects of stress on immune functions in medical students at exam
      time, and the comparison of self-hypnosis with and without immune imagery
      confirmed advantages to targeted imagery for both immune function and mood, and
      importantly, fewer winter viral infections. The implications for health were
      investigated in a third study in patients with virulent and chronic herpes
      simplex virus-2 HSV-2). Six weeks of training almost halved recurrence, improved
      mood and reduced levels of clinical depression and anxiety. Immune functions were
      up-regulated, notably functional natural killer cell activity to HSV-1.
      Individual differences in hypnotic susceptibility and absorption have typically
      been found to predict efficacy. New replicable evidence is reviewed of the
      importance of cognitive activation, a personality difference whose
      neurophysiological underpinning is consistent with left hemispheric preferential
      influences over the immune system. Now that the validation of psychological
      interventions includes advantages for health, this field of enquiry, which has
      been characterised by modest, small scale, largely preliminary studies, warrants
      a greater investment in research.

PMID- 12186694
TI  - Red cells with paroxysmal nocturnal hemoglobinuria-phenotype in patients with
      acute leukemia.
AB  - CD55 and CD59 are complement regulatory proteins that are linked to the cell
      membrane via a glycosyl-phosphatidylinositol anchor. They are reduced mainly in
      paroxysmal nocturnal hemoglobinuria (PNH) and in other hematological disorders.
      However, there are very few reports in the literature concerning their expression
      in patients with acute leukemias (AL). We studied the CD55 and CD59 expression in
      88 newly diagnosed patients with AL [65 with acute non-lymphoblastic leukemia
      (ANLL) and 23 with acute lymphoblastic leukemia (ALL)] using the sephacryl gel
      test, the Ham and sucrose lysis tests and we compared the results with patients'
      clinical data and disease course. Eight patients with PNH were also studied as
      controls. Red cell populations deficient in both CD55 and CD59 were detected in
      23% of ANLL patients (especially of M(0), M(2) and M(6) FAB subtypes), 13% of ALL
      and in all PNH patients. CD55-deficient erythrocytes were found in 6 ANLL
      patients while the expression of CD59 was decreased in only 3 patients with ANLL.
      No ALL patient had an isolated deficiency of these antigens. There was no
      correlation between the existence of CD55 and/or CD59 deficiency and the
      percentage of bone marrow infiltration, karyotype or response to treatment.
      However no patient with M(3), M(5), M(7) subtype of ANLL and mature B- or T-cell
      ALL showed a reduced expression of both antigens. The deficient populations
      showed no alteration after chemotherapy treatment or during disease course. This
      study provides evidence about the lower expression of CD55 and CD59 in some AL
      patients and the correlation with their clinical data. The possible mechanisms
      and the significance of this phenotype are discussed.

PMID- 12186695
TI  - Circulating and local bone marrow renin-angiotensin system in leukemic
      hematopoiesis: preliminary evidences.
AB  - Until last the decade, the renin-angiotensin system (RAS) was considered as a
      circulating endocrine system. It is now known that there are local RASs in many
      tissues. It has also recently been hypothesized that there exists a local bone
      marrow (BM) RAS with paracrine/autocrine pathobiological functions. The aim of
      this study was to detect BM and peripheral blood levels of the essential RAS
      components in normal and leukemic hematopoiesis. Concentrations of renin and
      angiotensin-converting enzyme (ACE) were assayed in BM aspirates and in
      simultaneously drawn peripheral blood samples of 16 pre-chemotherapy leukemic and
      10 post-treatment megaloblastic anemia patients with normal blood counts, as
      controls. In the leukemia group, the ACE concentration was found to be
      significantly higher in the BM (38+/-6.2 U/l) than in the peripheral blood
      (29.5+/-5.3 U/l), (p=0.029). In the leukemia group, although the BM renin
      concentration was higher than the peripheral blood levels (21.3+/-8.3 vs. 18.6+/
      6.2 U/l), this difference was not statistically significant (p=0.196). In the
      control group, mean BM renin levels were insignificantly lower than in the
      peripheral blood (8.6+/-3 vs. 12.1+/-4.6 pg/ml) (p=0.059). In the leukemia group,
      serum ACE levels positively correlated with BM and peripheral blood blast
      percentages (p<0.05). Serum LDH level (p<0.01), BM blast (p<0.05) and peripheral
      blast percentages (p<0.01) were inversely correlated with serum potassium in the
      leukemia group.The results of this study can be considered as the preliminary
      evidence supporting the hypothesis of the presence of a local BM RAS. Further,
      molecular biologic and immunohistochemical studies are needed to shed light on
      this important subject. A better understanding of the interrelationships of RAS
      and hematopoiesis will bring new insights into the pathobiology and even novel
      therapies for such neoplastic diseases.

PMID- 12186696
TI  - L and E selectins in acute myeloid leukemia: expression, clinical relevance and
      relation to patient outcome.
AB  - The aim of this study was to assess circulating soluble L (sL) and soluble E (sE)
      selectins adhesion molecules in acute myeloid leukemia (AML) blasts in order to
      evaluate their clinical significance. Fifty patients with AML (4 M0, 8 M1, 16 M2,
      5 M3, 7 M4, 6 M5, 4 M6) were included in this study. sL and sE selectins were
      evaluated at diagnosis, remission and in relapsed patients; whole membrane
      expression of L and E selectins by AML blast was investigated only at diagnosis.
      In addition, 15 normal persons were studied as a control group. sL and sE
      selectins were significantly higher in AML patients at diagnosis when compared to
      controls (P<0.01), but less at remission (P<0.01). Furthermore, elevated sL and
      sE selectin levels were detected in patients with AML at relapse. sE and sL
      selectins were significantly higher in AML patients with extramedullary
      infiltration as compared to patients without extramedullary disease (P<0.001).
      Membrane expression of L selectin was positive in 20% of AML patients. However,
      none of the patients showed significant E selectin expression. Patients with
      higher sE and sL selectins at diagnosis have high probability of relapse compared
      to those with normal levels (P<0.01 and <0.001, respectively). The overall
      relapse predictability of sE and sL selectins was 84%. Moreover, patients with
      higher sE and sL selectins levels had shorter event free survival than patients
      with lower levels (P<0.001 for both). The overall mortality prediction using sE,
      sL, and cellular L selectin was 96%. IN CONCLUSION: (1) AML blast cell express
      and release sL selectins but not sE selectin, (2) sE and sL selectins and
      cellular L selectin may be useful prognostic markers in evaluating AML patients
      at diagnosis.

PMID- 12186697
TI  - Immunohematological aspects of bone marrow transplantation.
AB  - Allogeneic bone marrow transplantation (BMT) is an effective treatment for some
      severe hematologic or nonhematologic diseases. The blood group antigen mismatch
      between donor and recipient may cause immunohematological complications during or
      after BMT. In this review, we analyze the ABO, Rh and other red cell antigen
      mismatches between donor and recipient, the main immunohematological
      complications and the techniques to prevent them. The data reported are derived
      from the experience of the authors and from the medical literature. The clinical
      implications of the immunohematological aspects of BMT emphasize the importance
      of close immunohematological monitoring in patients undergoing allogeneic BMT
      with ABO, Rh or other red cell antigen mismatches between donor and recipient.

PMID- 12186699
TI  - Successful reduced-intensity stem cell transplant from one-locus HLA-mismatched
      unrelated cord blood after rejection of unrelated bone marrow in an infant with
      myelogenous leukemia.
AB  - An 8-month-old girl had acute myelogenous leukemia (EAB M2) that relapsed 5
      months after diagnosis during intensive consolidation chemotherapy. She underwent
      bone marrow transplantation (BMT) from an HLA-A, -B, -C and -DR phenotypically
      matched, but one locus DRB1 genotypically mismatched unrelated donor, but
      rejection occurred.Subsequently, she received reduced-intensity transplant
      (fludarabine/cytosine arabinoside/cyclophosphamide) from one locus HLA-A
      mismatched, but DRB1 genotypically matched unrelated cord blood stem cells and
      remission was induced by acute GVHD (grade II) that progressed to chronic GVHD
      with involvement of the skin, liver, and gastrointestinal tract. In this case, it
      seems that remission was induced by an adequate graft-versus-leukemia effect and
      mild chronic graft-versus-disease due to the HLA-A difference more than DRB1
      matched between the patient and the cord blood stem cells.

PMID- 12186698
TI  - No cytomegalovirus-related deaths after non-ablative stem cell allografts.
AB  - Cytomegalovirus (CMV)-related deaths and data of clinically evident CMV disease
      were assessed in a group of 47 individuals given allogeneic non-myeloablative
      hematopoietic stem cell transplants (NST). IgG anti-CMV antibodies were found in
      56% of the donors and 76% of the receptors. Prophylactic ganciclovir was given to
      only 12 of the recipients during 100 days after the graft. There were no CMV
      related deaths and clinically overt CMV disease was not found in any individual.
      The follow up post-transplant period of the patients, ranges between 30 and 810
      days (median 242 days), the actuarial median survival (SV) is above 810 days and
      has not been reached, whereas the 810-days SV is 60%. Eighteen patients (38%)
      died 30-480 days after the transplant; four failed to engraft and died because of
      progressive disease; three died as a consequence of graft versus host disease
      (GVHD), whereas eleven individuals had a relapse of the malignancy and died. It
      is possible that the reduced bone marrow damage during NST, the prompt recovery
      of both the hematopoiesis and immune function in this type of allografts and the
      use of peripheral blood hematopoietic stem cell (HSC) is responsible for the
      absence of CMV-related deaths and clinical disease despite a high prevalence of
      CMV infection in these individuals.

PMID- 12186700
TI  - Elevation of serum KL-6 levels in patients with hematological malignancies
      associated with cytomegalovirus or Pneumocystis carinii pneumonia.
AB  - The level of serum KL-6 antigen has been reported to be a sensitive indicator of
      various interstitial pneumonitis, but in patients with hematological malignancies
      who were accompanied by infective interstitial pneumonitis like Pneumocystis
      carinii or cytomegalovirus (CMV) pneumonia, it is still unknown whether serum KL
      6 level is useful as a good marker for the diagnosis or disease activity. In this
      study, the serum levels of KL-6 and soluble intercellular adhesion molecule 1
      (sICAM-1) were evaluated in five patients with malignant lymphoma or adult T-cell
      leukemia. Serum KL-6 and sICAM-1 levels at the time of diagnosis of P. carinii or
      CMV pneumonia were 1220+/-323 U/ml (mean+/-SD) and 1246+/-485 ng/ml,
      respectively. These levels were apparently high, when compared with standard
      value of serum KL-6 (<520 U/ml) and that of sICAM-1 (115-306 ng/ml). In patients
      without P. carinii or CMV pneumonia, who had hematological malignancies or AIDS,
      serum level of KL-6 was not high (299+/-122 U/ml), but sICAM-1 was high (651+/
      495 ng/ml) because of the elevation of sICAM-1 in four of five cases. These
      findings suggest that, in patients with hematological malignancies, serum level
      of KL-6 antigen rather than sICAM-1 may be useful in the evaluation of CMV or P.
      carinii pneumonia.

PMID- 12186701
TI  - Recurrent acute myositis after allogeneic bone marrow transplantation for
      myelodysplasia.
AB  - A 54-year-old woman developed polymyositis 6 months after allogeneic bone marrow
      transplantation (BMT) for acute myelogenous leukemia transformed from
      myelodysplasia. At the onset of myositis, the patient had oral dryness, and the
      histology of oral mucosa was compatible with chronic graft-versus-host disease
      (GVHD). Muscle biopsy revealed focal muscle necrosis with massive lymphocytic
      infiltration. She was diagnosed with polymyositis, and the dose of cyclosporine
      was increased. Three months later, a complete resolution of myositis had been
      obtained, and the cyclosporine was tapered off. However, 51 months after the
      first episode of myositis, she again noted severe myalgia and was diagnosed with
      a recurrence of polymyositis based on high serum creatinine kinase (CK) and the
      findings of magnetic resonance imaging (MRI). At that time, chronic GVHD in other
      organs was not present. She achieved a second remission of polymyositis with
      cyclosporine, and has remained in remission for 4 years. The pathogenesis of
      myositis can be attributed to the immunologic imbalance characteristic of the
      post-allogeneic BMT setting.

PMID- 12186703
TI  - Major histocompatibility complex susceptibility genes and immune thrombocytopenic
      purpura in Caucasian adults.
AB  - Immune thrombocytopenic purpura (ITP) is a heterogeneous disorder with wide
      variability in response rates to treatments including corticosteroids,
      splenectomy and intravenous immune globulins. The nature of the underlying
      predisposing causes for this autoimmune disorder are not known. We have HLA typed
      71 adult Caucasian patients with chronic primary ITP, and compared the data with
      750 control samples. In this association study, we were not able to identify a
      significant immunogenetic susceptibility factor for ITP with HLA class I and
      class II alleles. However, it appeared that there might be an association between
      HLA-A2 and ITP, particularly in female patients, who are the predominantly
      affected group; and HLA-A2 was also present at increased frequency in patients
      with chronic ITP progressing to splenectomy. These findings are reviewed in the
      context of other similar reported HLA studies in ITP. Further studies based on
      larger groups of patients will be necessary to identify genetic susceptibility
      factors for this disease.

PMID- 12186702
TI  - MCP-1, MIP-1, IL-8 and ischemic cerebral tissue enhance human bone marrow stromal
      cell migration in interface culture.
AB  - Bone marrow stromal cells (MSCs) administered intravenously are effective in
      reducing neurological deficits after stroke in the rodent. These cells appear to
      selectively migrate and express neural phenotypes in ischemic brain. To elucidate
      the mechanisms targeting MSC migration into the ischemic brain, we measured,
      using a microchemotaxis chamber, the effect of select chemotactic factors and
      cytokines expressed in injured brain, monocyte chemoattractant protein-1 (MCP-1),
      macrophage inflammatory protein-1alpha (MIP-1alpha) and interleukin-8 (IL-8), on
      migration of human bone marrow stromal cells (hMSCs). In addition, we
      investigated whether tissue extracts prepared from rat ischemic brain at various
      times after middle cerebral artery occlusion (MCAo) induce migration of hMSCs.
      Our data indicate that MCP-1, MIP-1alpha and IL-8 enhance the migration of hMSCs.
      Ischemic brain tissue extracts at 24, 48 h and 1 week after ischemia
      significantly increase hMSC migration across the membrane compared to non
      ischemic tissue (p<0.05). These data indicate that hMSCs are targeted by
      inflammatory chemotactic agents and cytokines and that ischemic brain attracts
      hMSCs.

PMID- 12186705
TI  - Hematology morphology forum.

PMID- 12186706
TI  - Comparison of Cobb angles measured manually, calculated from 3-D spinal
      reconstruction, and estimated from torso asymmetry.
AB  - While scoliotic spinal deformity is traditionally measured by the Cobb angle, we
      seek to estimate scoliosis severity from the torso surface without X-ray
      radiation. Here, we measured the Cobb angle in three ways: by protractor from
      postero-anterior X-ray, by computer from a 3-D digitized model of the vertebral
      body line, and by neural-network estimation from indices of torso surface
      asymmetry. The estimates of the Cobb angle by computer and by neural network were
      equally accurate in 153 records from 52 patients (standard deviation of 6 degrees
      from the Cobb angle, r=0.93), showing that torso asymmetry reliably predicted
      spinal deformity. Further improvements in predictive accuracy may require
      estimation of other 3-D indices of spinal deformity besides the Cobb angle with
      its wide measurement variability.

PMID- 12186707
TI  - The effect of perfusion on soft tissue mechanical properties: a computational
      model.
AB  - Some simple finite element models were constructed to investigate the magnitude
      and character of changes in mechanical properties of very soft tissues due to the
      loss of perfusion. Changes in the apparent stress-strain curve were used to
      characterise the effect of simulated blood perfusion pressure on the engineering
      stress-strain curve. The results indicated that the blood to tissue volume ratio
      and the perfusion pressure have the strongest effect on the effective stress
      strain response of a representative tissue cell. Tissue viscoelasticity increased
      the sensitivity of the system to perfusion pressure changes.

PMID- 12186708
TI  - Development of an accurate three-dimensional finite element knee model.
AB  - This paper presents the development of a detailed articulating three-dimensional
      finite-element model of the human knee, derived from MRI scan images. The model
      utilises precise material models and many contact interfaces in order to produce
      a realistic kinematic response. The behaviour of the model was examined within
      two fields of biomechanical simulations: general life and car-crash. These
      simulations were performed with the non-linear explicit dynamic code PAM-SAFE
      trade mark. The knee model produced results that compared favourably with
      existing literature. Such a model (together with other joint models that could be
      constructed using the same techniques) would be a valuable tool for examining new
      designs of prosthesis and mechanisms of injury.

PMID- 12186709
TI  - Numerical analysis of titanium cast devices for dental implantology.
AB  - The present work pertains to a numerical investigation of the casting process of
      titanium devices adopted for dental implantology. The analysis of the titanium
      framework that connects different abutments, in a multi-implant configuration, is
      performed evaluating the characteristics of the material that depend on the
      manufacturing procedure. The connecting bar is obtained by a foundry process that
      is controlled through a numerical simulation by using a control volume technique.
      This analysis leads to the possibility to have detailed information on the
      process and control of the quality of the microstructure of the material produced
      that proves to be highly beneficial for defining mechanical properties. On the
      basis of the results obtained, a subsequent stress analysis can be performed,
      addressed to highlight critical conditions. Functional response of the whole bar
      implant framework is studied by means of a numerical model, based on the
      geometric element method. This technique is particularly suited for describing
      complex morphology of the implant site. The present approach addresses a higher
      quality definition of the reliability of the device used in dental practice and
      represents a valuable tool in assisting optimisation procedures pertaining to
      manufacturing. In fact, the improvement of titanium devices is intended not only
      with regard to their mechanical performances, but also to requirements pertaining
      to manufacturing and clinical practice.

PMID- 12186710
TI  - Flow-induced wall shear stress in abdominal aortic aneurysms: Part I--steady flow
      hemodynamics.
AB  - Numerical predictions of blood flow patterns and hemodynamic stresses in
      Abdominal Aortic Aneurysms (AAAs) are performed in a two-aneurysm, axisymmetric,
      rigid wall model using the spectral element method. Homogeneous, Newtonian blood
      flow is simulated under steady conditions for the range of Reynolds numbers 10 <
      or =Re < or =2265. Flow hemodynamics are quantified by calculating the
      distributions of wall pressure (p(w)), wall shear stress (tau(w)), Wall Shear
      Stress Gradient (WSSG). A correlation between maximum values of hemodynamic
      stresses and Reynolds number is established, and the spatial distribution of WSSG
      is considered as a hemodynamic force that may cause damage to the arterial wall
      at an intermediate stage of AAA growth. The temporal distribution of hemodynamic
      stresses in pulsatile flow and their physical implications in AAA rupture are
      discussed in Part II of this paper.

PMID- 12186711
TI  - Flow-induced wall shear stress in abdominal aortic aneurysms: Part II--pulsatile
      flow hemodynamics.
AB  - In continuing the investigation of AAA hemodynamics, unsteady flow-induced
      stresses are presented for pulsatile blood flow through the double-aneurysm model
      described in Part I. Physiologically realistic aortic blood flow is simulated
      under pulsatile conditions for the range of time-average Reynolds numbers 50< or
      =Re(m) < or =300. Hemodynamic disturbance is evaluated for a modified set of
      indicator functions which include wall pressure (p(w)), wall shear stress
      (tau(w)), Wall Shear Stress Gradient (WSSG), time-average wall shear stress
      (tau(w)*), and time-average Wall Shear Stress Gradient WSSG*. At peak flow, the
      highest shear stress and WSSG levels are obtained at the distal end of both
      aneurysms, in a pattern similar to that of steady flow. The maximum values of
      wall shear stresses and wall shear stress gradients are evaluated as a function
      of the time-average Reynolds number resulting in a fourth order polynomial
      correlation. A comparison between numerical predictions for steady and pulsatile
      flow is presented, illustrating the importance of considering time-dependent flow
      for the evaluation of hemodynamic indicators.

PMID- 12186712
TI  - A one-dimensional finite element method for simulation-based medical planning for
      cardiovascular disease.
AB  - We have previously described a new approach to planning treatments for
      cardiovascular disease, Simulation-Based Medical Planning, whereby a physician
      utilizes computational tools to construct and evaluate a combined
      anatomic/physiologic model to predict the outcome of alternative treatment plans
      for an individual patient. Current systems for Simulation-Based Medical Planning
      utilize finite element methods to solve the time-dependent, three-dimensional
      equations governing blood flow and provide detailed data on blood flow
      distribution, pressure gradients and locations of flow recirculation, low wall
      shear stress and high particle residence. However, these methods are
      computationally expensive and often require hours of time on parallel computers.
      This level of computation is necessary for obtaining detailed information about
      blood flow, but likely is unnecessary for obtaining information about mean flow
      rates and pressure losses. We describe, herein, a space-time finite element
      method for solving the one-dimensional equations of blood flow. This method is
      applied to compute flow rate and pressure in a single segment model, a
      bifurcation, an idealized model of the abdominal aorta, in three alternate
      treatment plans for a case of aorto-iliac occlusive disease and in a vascular
      bypass graft. All of these solutions were obtained in less than 5 min of
      computation time on a personal computer.

PMID- 12186713
TI  - Simulation of flow through a Miller cuff bypass graft.
AB  - Unnatural temporal and spatial distributions of wall shear stress in the
      anastomosis of distal bypass grafts have been identified as possible factors in
      the development of anastomotic intimal hyperplasia in these grafts. Distal bypass
      graft anastomoses with an autologus vein cuff (a Miller cuff) interposed between
      the graft and artery have been shown to alleviate the effects of intimal
      hyperplasia. In this study, pulsatile flow through models of a standard end-to
      side anastomosis and a Miller cuff anastomosis are computed and the resulting
      wall shear stress and pressure distributions analysed. The results are
      inconclusive, and could be taken to suggest that the unnatural distributions of
      shear stress that do occur along the anastomosis floor may not be particularly
      important in the development of intimal hyperplasia. However, it seems more
      likely that the positive effects of the biological and material properties of the
      vein cuff, which are not considered in this study, somehow outweigh the negative
      effects of the shear stress distributions predicted to occur on the floor of the
      Miller-cuff graft.

PMID- 12186714
TI  - Pulsatile flow inside moderately elastic arteries, its modelling and effects of
      elasticity.
AB  - Pulsatile flow inside a moderately elastic circular conduit with a smooth
      expansion is studied as a model to understand the influence of wall elasticity in
      artery flow. The solution of the simultaneous fluid-wall evolution is evaluated
      by a perturbative method, where the zeroth order solution is represented by the
      flow in a rigid vessel; the first order correction gives the wall motion and
      induced flow modification without the need to solve the difficult coupled
      problem. Such an approach essentially assumes a locally infinite celerity,
      therefore it represent a good approximation for the fluid-wall interaction in
      sites of limited extent (branches, stenosis, aneurism, etc.), which include
      typical situations associated with vascular diseases. The problem is solved
      numerically in the axisymmetric approximation; the influence of wall elasticity
      on the flow and on the unsteady wall shear stress is studied in correspondence of
      parameters taken from realistic artery flow. Attention is posed to the role of
      phase difference between the incoming pressure and flow pulses.

PMID- 12186715
TI  - Coupled computational analysis of arterial LDL transport -- effects of
      hypertension.
AB  - Hypertension, a risk factor for atherosclerosis, increases the uptake of low
      density lipoproteins (LDL) by the arterial wall. Our objective in this work was
      to use computational modeling to identify physical factors that could be
      partially responsible for this effect. Fluid flow and mass transfer patterns in
      the lumen and wall of an arterial model were computed in a coupled manner,
      replicating as closely as possible previous experimental studies in which LDL
      uptake into the artery wall was measured in straight, excised arterial segments.
      Under conditions of both flow and no-flow, simulations predicted an increase in
      concentration polarization of LDL at the artery wall when arterial pressure was
      increased from 120 to 160 mmHg. However, this led to only a slight increase in
      mean LDL concentration within the arterial wall. However, if the permeability of
      the endothelium to LDL was allowed to vary with intra-arterial pressure, then the
      simulations predicted that the uptake of LDL would be enhanced 1.9-2.6 fold at
      higher pressure. The magnitude of this increase was consistent with experimental
      data. We conclude that the concentration polarization effects, enhanced by
      elevated intra-arterial pressure, cannot explain the increase in LDL uptake seen
      under hypertensive conditions. Instead, the data are most consistent with a
      pressure-linked increase in endothelial permeability to LDL.

PMID- 12186716
TI  - Pressure drops in a distensible model of end-to-side anastomosis in systemic-to
      pulmonary shunts.
AB  - The modified Blalock-Taussig shunt is a surgical procedure used as a palliation
      to treat complex congenital heart defects. It consists of an interposing
      prosthetic tube between the innominate/subclavian artery and the right pulmonary
      artery. Previous experience indicates that the pressure drop across the shunt is
      affected by the pulmonary pressure at the distal anastomosis combined with the
      distensibility of the anastomosis. In this study, a computational fluid-structure
      interaction approach is presented to investigate the haemodynamic behaviour.
      Steady-state fluid dynamics and structural analyses were carried out using
      commercial codes based on the finite element method (FIDAP and ABAQUS) coupled by
      means of a purposely-developed procedure to transfer boundary conditions. Both
      prosthetic tube and artery walls were characterised by non-linear material
      properties. Three different pulmonary pressures (2, 5 and 15 mmHg) and two volume
      flow rates (0.4 and 0.8 l/min) were investigated. Results indicate that the
      effects of distensibility at the distal anastomosis on the shunt pressure drop
      are relevant only when the distal anastomosis on the shunt pressure drop are
      relevant only when the distal anastomosis is not fully distended, which occurs
      when the pulmonary pressure is lower than 5 mmHg.

PMID- 12186717
TI  - Computational fluid dynamics modeling and analysis of the effect of 3-D
      distortion of the human aortic arch.
AB  - An idealized CFD model and a realistic one were used to investigate the effect of
      the 3-D distortion of the aortic arch on the blood flow and its
      pathophysiological significance with respect to the pathogenesis of the aortic
      aneurysm. From the results of the flow simulations, the distortion of the
      centerline of the pipe was shown to affect significantly the flow structure. A
      right-handed vortex at the descending arch, and a left-handed one at the end of
      the arch tended to develop in the realistic model. But the secondary flow did not
      become a single helix. The top of the arch was the region where complex spatial
      and temporal WSS distributed. It was also observed that the direction of WSS had
      a significant circumferential component at the top of the arch.

PMID- 12186718
TI  - Vortical flow structure identification and flow transport in arteries.

PMID- 12186719
TI  - A nonlinear elastic model of the periodontal ligament and its numerical
      calibration for the study of tooth mobility.
AB  - A large strain nonlinear elastic isotropic "split" law is proposed for modeling
      the behaviour of the periodontal ligament. This law allows for a better
      description of the stiffening response of this tissue and, concomitantly, for a
      more accurate calibration of its elastic properties. Indeed, fine finite element
      simulations of an upper human incisor attached to its surrounding alveolar bone
      by an intermediate layer of ligament were run using that "split" law for the
      ligament. A good correlation was established with available experimental data on
      such a tooth under axial loading. Values of 0.010-0.031 MPa for the initial
      Young's modulus and of 0.45-0.495 for Poisson's ratio were determined. A
      sensitivity analysis of the results with respect to material and numerical
      parameters of the model was also carried out. Finally, a comparison of the
      simulation results using this "split" law with standard ones obtained with the
      linear elastic law, shows a significant improvement.

PMID- 12186720
TI  - Parametric finite element analysis and closed-form solutions in orthodontics.
AB  - The goal and clinical relevance of this work was the development of closed
      formulas that are correct and simple enough for a fast decision making by the
      orthodontist in the daily praxis. This paper performs a parametric three
      dimensional finite element linear analysis on a maxillary central incisor with a
      root of paraboloidal shape, which is subjected to typical orthodontic force
      systems. Parameters of most importance, such as the tooth mobility in translation
      and in pure moment rotation including orthodontic centers, as well as the
      stresses inside the periodontal ligament are calculated for a large variety of
      over four hundred different couples of root lengths and root diameters around a
      nominal value. Regression analysis is afterwards performed and establishes closed
      form solutions, which are also explained in terms of analytical strain energy and
      hydrostatic stress considerations within the periodontal ligament characterised
      by a small compressibility. The obtained expressions include both the root length
      as well as the root diameter.

PMID- 12186722
TI  - A comparative analysis based on different strength criteria for evaluation of
      risk factor for dental implants.
AB  - A numerical analysis is developed to study the interaction phenomena between
      endousseus titanium dental implants and surrounding jawbone tissue. The interest
      is focused on the most appropriate evaluation of the stress state arising in the
      tissue because of the implant under physiological loading. The problem is
      considered with regard to linear elastic response of the one and to short time
      effect. Different configurations of bone-implant system are described, using
      axial-symmetrical and three-dimensional models, by means of finite and geometric
      element method. The investigation attains to the stress states induced in bone
      that lead to a limit condition near the effective failure surface. The parameter
      commonly adopted in literature, such as the Von Mises stress, represents an
      excessive simplification of problem formulation, leading to an incorrect
      evaluation of the real failure risk for the implant, due to the assumption of the
      isotropic and deviatoric nature of the adopted stress measure. More suitable
      criterion can be assumed, such as the Tsai-Wu criterion, to take into account the
      anisotropy that characterises the response of bone, as well as the influence of a
      hydrostatic stress state. The analysis developed offers a comparison of results
      by using different criteria, leading to an evaluation of reliability of the
      procedure to be followed and addressing also to an evaluation of a risk factor
      for the implant investigated.

PMID- 12186721
TI  - A model of the structural and functional development of the normal human fetal
      left ventricle based on a global growth law.
AB  - The purpose of this research is to study the growth of the normal human left
      ventricle (LV) during the fetal period from 14 to 40 weeks of gestation. A new
      constitutive law for the active myocardium describing the mechanical properties
      of the active muscle during the whole cardiac cycle has been proposed. The LV
      model is a thick-walled, incompressible, hyperelastic cylinder, with families of
      helicoidal fibers running on cylindrical surfaces [1]. Based on the works of Lin
      and Taber [2] done on the embryonic chick heart, we use for the human fetal heart
      a growth law in which the growth rate depends on the wall stresses. The
      parameters of the growth law are adapted to agree with sizes and volumes inferred
      from two dimensional ultrasound measurements performed on 18 human fetuses.Then
      calculations are performed to extrapolate the cardiac performance during normal
      growth of the fetal LV. The results presented support the idea that a growth law
      in which the growth rate depends linearly on the mean wall stresses averaged
      through the space and during whole cardiac cycle, is adapted to the normal human
      fetal LV development.

PMID- 12186723
TI  - Computational analysis of micron-particle deposition in a human triple
      bifurcation airway model.
AB  - Steady laminar axisymmetric inhalation flow and wall deposition of micron-size
      particles in representative triple bifurcation airways have been simulated using
      a commercial finite-volume code with user-enhanced programs. Assuming spherical
      non-interacting particles (3 microm</=d(p)</=7 microm), various inlet Reynolds
      numbers (Re=500-2000) and Stokes numbers (St=0.02-0.23) were considered. The
      resulting particle deposition patterns were analyzed and then summarized in terms
      of deposition efficiencies, i.e. DE=DE(Re,St) Surprisingly high DE-values occur
      at relatively low Reynolds numbers (e.g., Re=500) in the third bifurcation. The
      quantitative results are of interest to researchers either conducting health risk
      assessment studies for inhaled particulate pollutants or analyzing drug aerosol
      inhalation and deposition at desired lung target sites.

PMID- 12186724
TI  - A dynamic model of the knee and lower limb for simulating rising movements.
AB  - A two-dimensional dynamical model of the human body was developed and used to
      simulate muscle and knee-ligament loading during a fast rising movement. The hip,
      ankle, and toes were each modeled as a simple hinge joint. Relative movements of
      the femur, tibia, and patella in the sagittal plane were described using a more
      detailed representation of the knee. The geometry of the model bones was adapted
      from cadaver data. Eleven elastic elements described the geometric and mechanical
      properties of the knee ligaments and joint capsule. The patella was assumed to be
      massless. Smooth hypersurfaces were constructed and used to calculate the
      position and orientation of the patella during a forward integration of the
      model. Each hypersurface was formed by applying the principle of static
      equilibrium to approximate patellofemoral mechanics during the simulation. The
      model was actuated by 22 musculotendinous units, each unit represented as a three
      element muscle in series with tendon. A first-order process was assumed to model
      muscle excitation-contraction dynamics. Dynamic optimization theory was used to
      calculate the pattern of muscle excitations that produces a coordinated rising
      movement from an initial squatting position in minimum time. The calculations
      support the contention that squatting is a relatively safe exercise for
      rehabilitation following ACL reconstruction. ACL forces remain less than 20 N for
      the duration of the task.

PMID- 12186725
TI  - Personalised mechanical properties of scoliotic vertebrae determined in vivo
      using tomodensitometry.
AB  - This in vivo study investigated the mechanical properties of apical scoliotic
      vertebrae using computed tomography (CT) and finite element (FE) meshing. CT
      examination was performed on seven scoliotic girls. FE meshing of each vertebral
      body allowed automatic mapping of the CT scan and the visualisation of the bone
      density distribution. Centroids and mass centres were compared to analyse the
      mechanical properties distribution. Compared to the centroid, the mass centre
      migrated into the concavity of the curvature. The three vertebrae of a same
      patient had the same body migration behaviour because they were located at the
      curvature apex. This observation was verified in the coronal plane, but not in
      the sagittal plane. These results represent new data over few geometrical
      analyses of scoliotic vertebrae. Same in vivo personalisation of mechanical
      properties should be performed on intervertebral discs or ligaments to
      personalise stiffness properties of the spine for the biomechanical modelling of
      human torso. Moreover, do this mechanical deformation of scoliotic vertebrae,
      that appears before the vertebral wedging, could be a predictive tool in
      scoliosis treatment?

PMID- 12186726
TI  - A visco-hyperelastic model with damage for the knee ligaments under dynamic
      constraints.
AB  - The aim of this study was to identify the behaviour laws governing the knee
      ligaments, accounting for the damage incurred by the structure under dynamic
      constraints. The model is developed using a thermodynamic formulation based on
      the coupling between a viscoelastic model and a damage model. Identification is
      carried out using the results of dynamic traction tests performed on a bone
      ligament/bone complex to which traction velocities of around 1.98 m/s were
      applied. The results show the ability of the model to account for the brittle and
      ductile failure processes occurring in the cruciate and lateral ligaments,
      respectively.

PMID- 12186727
TI  - Comparison of three kinematic analyses of the knee: determination of intrinsic
      features and applicability to intraoperative procedures.
AB  - The evaluation of knee motion is an important step for correct diagnoses and
      optimal surgical reconstructions, but controversial opinions still remain about
      the most suitable numerical method for the elaboration of clinical kinematic
      tests. In this paper, we present a comparison of three methods applied to an
      experimental animal study (Grood and Suntay method [Grood, E.S. and Suntay, W.J.
      (1983) "A coordinate system for the clinical description of three-dimensional
      motions: application to the knee", J. Biomech. Engng, 105, pp. 136-144], Helical
      Axes method [Blankevoort, L., Huiskes, R. and de Lange, A. (1990). "Helical axes
      of passive knee joint motions", J. Biomech., 23 pp. 1219-1229] and Functional
      method [Martelli, S., Zaffagnini, S., Falcioni, B. and Marcacci, M. (2000).
      "Intraoperative kinematic protocol for knee joint evaluation", Comput. Methods
      Programs Biomed., 62 pp. 77-86]). The study shows the numerical differences among
      the three protocols and evaluates their performances and repeatability during
      clinical tests, i.e. laxity measurements and passive range of motion. The
      Functional method gives the optimal compromise among accuracy, clinical
      interpretability and ease of use for intraoperative kinematic evaluations.

PMID- 12186728
TI  - Computer determination of contact stress distribution and size of weight bearing
      area in the human hip joint.
AB  - The mathematical models and the corresponding computer program for determination
      of the hip joint contact force, the contact stress distribution, and the size of
      the weight bearing area from a standard anteroposterior radiograph are described.
      The described method can be applied in clinical practice to predict an optimal
      stress distribution after different operative interventions in the hip joint and
      to analyze the short and long term outcome of the treatment of various
      pathological conditions in the hip. A group of dysplastic hips and a group of
      normal hips were examined, with respect to the peak contact stress normalized by
      the body weight, and with respect to the functional angle of the weight bearing
      area. It is shown that both these parameters can be used in the assessment of hip
      dysplasia.

PMID- 12186729
TI  - Interrelations between elastic energy and strain in a tensegrity model:
      contribution to the analysis of the mechanical response in living cells.
AB  - Interactions between the physical and physiological properties of cellular sub
      units result in changes in the shape and mechanical behaviour of living tissues.
      To understand the mechanotransmission processes, models are needed to describe
      the complex interrelations between the elements and the cytoskeletal structure.
      In this study, we used a 30-element tensegrity structure to analyse the influence
      of the type of loading on the mechanical response and shape changes of the cell.
      Our numerical results, expressed in terms of strain energy as a function of the
      overall deformation of the tensegrity structure, suggest that changes in cell
      functions during mechanical stimuli for a given potential energy are correlated
      to the type of loading applied, which determines the resultant changes in cell
      shape. The analysis of these cellular deformations may explain the large
      variability in the response of bone cells submitted to different types of
      mechanical loading.

PMID- 12186730
TI  - Numerical models of auto-regulation and blood flow in the cerebral circulation.
AB  - A two-dimensional time-dependent computational fluid dynamics model of the Circle
      of Willis has been developed. To simulate, not only the peripheral resistance of
      the cerebrovascular tree but also its auto-regulation function, a new "active"
      boundary condition has been defined and developed using control theory to provide
      a model of the feedback mechanism. The model was then used to simulate different
      common abnormalities of the Circle of Willis while a pressure drop, simulating a
      rapid compression of the right internal carotid artery, was imposed. Test results
      using a simple tube compared excellently with experiment. The total time
      dependent flux for each efferent artery was tabulated and showed the important
      relationship between geometrical variations in the Circle of Willis and the auto
      regulation of blood flow by vascular vaso-dilation and contraction. From this
      study, it was found that the worst case seemed to be that of a missing or
      dysfunctional right A1 segment of the anterior cerebral artery. The use of valid
      physiological models of the peripheral resistance allows for more realistic
      models of the blood flow in the Circle whilst allowing an easy extension to 3D
      patient specific simulations.

PMID- 12186731
TI  - A voxel-based formulation for contact finite element analysis.
AB  - To date, voxel-based finite element models have not been feasible for contact
      problems, owing to the inherent stair-step boundary discontinuities. New
      preprocessing techniques are reported herein to mesh these boundaries smoothly,
      for purposes of contact stress analysis. Further, new techniques are reported to
      concentrate the mesh resolution automatically near the articular surface, thus
      reducing the problem size to levels compatible with executing nonlinear problems
      on contemporary engineering workstations. Close approximations to Hertzian
      analytical solutions were obtained for spherical and cylindrical geometries
      meshed in this manner, and an illustrative anatomical contact problem of the
      human hip joint is presented.

PMID- 12186732
TI  - Forward-dynamics simulation of anterior cruciate ligament forces developed during
      isokinetic dynamometry.
AB  - A mathematical (computer) model was developed and used to study the mechanics of
      the human knee during extension exercises employing an isokinetic dynamometer.
      All parts of the body were fixed to ground, except for the right shank and foot,
      which were free to move in the parasagittal plane. A linkage attached the
      dynamometer to the shank; tibiofemoral articulation consisted of single-point
      contact, allowing both sliding and rolling to occur. Physiologically based
      representations of ligaments and muscles imparted forces to the shank. A forward
      dynamics simulation was performed to calculate the forces developed in the knee
      for isokinetic speeds ranging from 0 (isometric exercise) to 300 degrees /s.
      Simulations were conducted for a constant-speed phase during isokinetic knee
      extension exercise. It was assumed for the duration of each simulated exercise
      that the quadriceps were fully activated and the other muscles were fully
      deactivated. The force in the anterior cruciate ligament was found to be governed
      by the force-velocity properties of the quadriceps; the model predicts that 300
      deg/sec isokinetic exercise can reduce the force transmitted to the ACL by almost
      a factor of two compared with that present during isometric knee extension.

PMID- 12186733
TI  - Alterations in mechanical behaviour of articular cartilage due to changes in
      depth varying material properties--a nonhomogeneous poroelastic model study.
AB  - The depth dependence of the material properties is present in normal adult
      cartilage and is believed to have significant implications in its normal
      mechanical function. Cartilage pathology may alter the depth dependence, e.g. a
      reduced depth dependence of the fibril stiffness has been observed in
      osteoarthritic cartilage. The objective of the present study is to investigate
      the alterations in the mechanical response of articular cartilage when the depth
      dependence of the material properties is varied to simulate healthy and
      pathological situations. This study is made possible by a recently developed
      nonhomogeneous poroelastic model. Depth variations of the strains and stresses
      for individual material phases (collagen, proteoglycan and fluid) are obtained
      for cartilage disks in unconfined compression using the finite element method.
      The mean nominal axial strain considered is up to 15%, while the axial strain at
      the articular surface can reach 33%. This paper demonstrates how the mechanical
      behaviours of cartilage are affected by individual depth dependent cartilage
      properties, while such observations are not fully available in experimental
      investigations. This study suggests the possibility of diagnosing cartilage
      health by analysing its mechanical behaviours.

PMID- 12186734
TI  - Numerical analysis of an anastomotic device.
AB  - The explicit dynamic finite element method was utilized to investigate the
      deformation behaviour of a woven wire mesh tubular device that is used in a side
      to-side anastomotic procedure for achieving gastrointestinal anastomosis. The
      numerical model was initially verified by comparison to experimental results that
      were obtained using a specialized testing mechanism. Once validated, the finite
      element model (FEM) was parameterized to ascertain the influence of several
      device parameters on its deformation behaviour. The importance of these
      parameters, as related to its optimal design for use in minimally invasive
      surgery (MIS), was subsequently ascertained and discussed.

PMID- 12186735
TI  - A mathematical model of the stability control of human thorax and pelvis
      movements during walking.
AB  - A mathematical model is developed to study the human thorax and pelvis movements
      in the frontal plane during normal walking. The model comprises of two-link base
      excited inverted pendulums with one-degree of rotational freedom for each link.
      Since the linear motion of the pelvis has a significant effect on the upper body
      stability, this effect is included in the model by having a base point moving in
      the frontal plane in a general way. Furthermore, because the postural stability
      is the primary requirement of normal human walking, the control law is developed
      based on Lyapunov's stability theory, which guarantees the stability of the
      pendulum system around the up-right position. To evaluate the model, the
      simulation results, including the angular displacement of each link and the
      torque applied on each link, are compared with those from gait measurements. It
      is shown that the simulation results match those from gait measurements closely.
      These results suggest that the proposed model can provide a useful framework for
      analysis of postural control mechanisms.

PMID- 12186736
TI  - Numerical analysis of models of the standard TSRH spinal instrumentation: effect
      of rod cross-sectional shape.
AB  - A numerical technique, geometric element modeling and analysis, was used to
      investigate the effect of the cross-sectional shape of the rod (circular versus
      square) in three-dimensional models of the standard (dual-rod) Texas Scottish
      Rite Hospital (TSRH) spinal instrumentation on two biomechanical characteristics
      (namely, stiffness and the von Mises equivalent stress) of the instrumentation
      under compressive force and torque, applied separately. The model constraints are
      the same as those acting on the instrumentation clinically, that is, when it is
      attached to the vertebrae of the human spine. Furthermore, the magnitudes of the
      compressive and torsional loadings applied on the model are within the range of
      those experienced by the spine during normal walking. It was found that use of
      square cross-sectioned rods leads to better biomechanical performance of the
      model compared to the case when the rods are circular. This finding points the
      way to the possibility of using square cross-sectioned rods in the TSRH
      instrumentation.

PMID- 12186737
TI  - Distributed body weight over the whole spine for improved inference in spine
      modelling.
AB  - Numerous models used to investigate the causes of low back pain are based upon
      the concept of the lever model that considers equilibrium of forces and moments
      about a single intervertebral joint. Consideration of forces and moments at each
      intervertebral joint is essential if a more realistic idea of the loading on the
      spine is to be obtained. This will also allow the role of the curvature of the
      spine to be investigated. A distributed loading pattern for forces due to body
      weight for the whole spine has not been investigated before. In this paper, a
      distributed loading pattern for the whole spine for various postures is
      investigated and the potential impact on the calculations is discussed.

PMID- 12186738
TI  - Amadori product and age formation during nonenzymatic glycosylation of bovine
      serum albumin in vitro.
AB  - Glucose reacts with the amino groups of protein to form a Schiff base that
      rearranges to form a ketoamine adduct. These early products eventually undergo
      irreversible chemical modifications generating advanced glycation end products
      (AGES). We reacted various sugars and sugar phosphates with bovine serum albumin
      allowing the formation of Amadori and AGE products. The rates of browning,
      Amadori and AGE products formed during incubations at 37 and 55 degrees C were
      compared. The correlation between AGE fluorescence and bitopical (crosslinking)
      modifications in the protein have been evaluated. Pentoses generated maximum
      Amadori products. Sugar phosphates were found to be more potent in generating
      AGEs than free sugars as measured by fluorescence. Though glucose, fructose and
      glucose-6-P do not generate fluorescence comparable to pentoses, they generate
      high molecular weight aggregates. In contrast, ribose-5-P, which shows
      significantly higher AGE and pentosidine fluorescence than the other sugars, did
      not generate high molecular weight aggregates. We suggest that there may not be a
      direct correlation between the levels of Amadori products, AGEs and crosslinking.

PMID- 12186739
TI  - Glu 103 Gln site-directed mutation causes an alteration in physical properties of
      spinach betaine aldehyde dehydrogenase.
AB  - Site-directed mutant of spinach betaine aldehyde dehydrogenase (BADH) was
      obtained by replacing Glu 103 with Gln 103 and the resulting E 103 Q mutant was
      expressed in Escherichia coli. The mutant BADH as compared to the wild-type BADH
      was slightly more sensitive to inhibition by NaCl but less sensitive to
      inhibition by (NH(4))(2)SO(4). Glycinebetaine (GB) activated the wild-type enzyme
      but not the mutant enzyme. Stronger inhibition by choline was observed in the
      mutant enzyme than in the wild-type enzyme whereas the reverse was observed for
      the inhibition by isovaleraldehyde. The mutant enzyme exhibited a broader
      temperature optimum than the wild-type enzyme, however, the mutant enzyme
      appeared to be more heat labile. Both mutant and wild-type enzymes could be
      protected by NAD(+) against thermal inactivation in a similar manner. However,
      neither GB nor NaCl could afford protection against thermal inactivation in the
      mutant enzyme whereas some protection was observed in the wild-type enzyme.
      Similar pH activity profile was obtained for both mutant and wild-type enzymes.
      The mutant enzyme was less stable than the wild-type enzyme under the pH range of
      5-11. Overall results suggest that the negative charge of Glu 103 at the surface
      of the spinach BADH plays some roles in the maintenance of the structural
      integrity of the enzyme.

PMID- 12186740
TI  - Isolation, identification and characterization of chicken anaemia virus in
      Malaysia.
AB  - A study was conducted to isolate and identify chicken anaemia virus (CAV) from
      field samples of clinically infected broiler chickens in Malaysia. A total of 125
      samples were collected from chickens aged 2-6 weeks with clinically depressed and
      retarded growth, of which five samples were found positive to CAV directly by
      polymerase chain reaction (PCR). Later, five isolates of CAV from the respective
      five PCR positive samples were isolated in MDCC-MSB1 cells at passage 4 based on
      cytopathic effects, PCR and indirect immunofluorescent antibody test. The
      isolates were identified as BL-1, BL-2, BL-3, BL-4 and BL-5. These CAV isolates
      were found to resist treatment with chloroform and heat at 37 degrees C for 2 h,
      56 degrees C for 30 min and 70 degrees C for 5 min. One of the isolates, BL-5
      produced significant reduction (p < 0.001) of hematocrit values (9-19%), pale
      bone marrow, thymus atrophy and haemorrhages in skin/muscle when inoculated into
      1-day old SPF chickens. Restriction enzyme digestion of 926 bp genomic fragments
      of all the isolates including Cux-1 isolate with HindIII exhibited a similar
      pattern of bands in 2% agarose gel. The present findings confirmed the presence
      of CAV in Malaysia.

PMID- 12186741
TI  - Induction of glutathione-dependent hepatic biotransformation enzymes by lycopene
      in the hamster cheek pouch carcinogenesis model.
AB  - Consumption of carotenoids is recognised to be inversely related with cancer
      incidence. Lycopene, a major carotenoid in tomatoes is a potent antioxidant with
      potential anticarcinogenic properties. We undertook the study to investigate the
      effect of lycopene on hepatic biotransformation enzymes during 7,12
      dimethylbenz[a]anthracene (DMBA)-induced hamster buccal pouch (HBP)
      carcinogenesis using hepatic lipid peroxidation, reduced glutathione (GSH) and
      biotransformation enzymes that use GSH as a substrate such as glutathione
      peroxidase (GPx), glutathione-S-transferase (GST) and glutathione reductase (GR).
      Enhanced lipid peroxidation in the liver of tumour-bearing animals was
      accompanied by significant decreases in the activities of GSH and GSH-dependent
      enzymes. Administration of lycopene significantly decreased the formation of
      lipid peroxides and enhanced the activities of hepatic biotransformation enzymes.
      Our results indicate that elevation of hepatic GSH and biotransformation enzymes
      by lycopene may play a key role in preventing cancer development at extrahepatic
      sites.

PMID- 12186742
TI  - New peptidomimetics of insulin.
AB  - New peptidomimetics that have been obtained in the course of our experimental
      work show distinct insulin-like activity both in vitro and in vivo. The first
      peptidomimetic (PM 1) is essentially a decapeptide in which sites of A (20-21)
      and B (19-26) chains of insulin are linked by the peptides bond (Cys-Gly-Glu-Arg
      Gly-Phe-Phe-Tyr-Cys-Asn). The second peptidomimetic (PM 2) has similar set of
      amino acid residues, except that two aromatic amino acids corresponding to the
      residues of B chain of insulin (B24 and B26) have been replaced with their D
      optical isomers (Cys-Gly-Glu-Arg-Gly-DPhe-Phe-DTyr-Cys-Asn). The third
      peptidomimetic (PM 3) has been obtained through acylation of N-terminal of PM 1
      by the use of palmitic acid. The peptidomimetic incorporating D aromatic amino
      acids (PM 2) was demonstrated to exhibit more pronounced hypoglycemic impact,
      while the acylation of decapeptide tends to prolong the effective time of
      peptidomimetic influence in vivo.

PMID- 12186743
TI  - Effect of radiation induced lipid peroxidation on diphenylhexatriene fluorescence
      in egg phospholipid liposomal membrane.
AB  - Ionizing radiation induced chemical/structural modification in liposomes and
      related changes in fluorescence intensity of incorporated 1,6-diphenyl 1,3,5
      hexatriene (DPH) was investigated in egg lecithin unilamellar vesicles. A
      correlation was found to exist between the magnitude of malondialdehyde (MDA)
      formation and the fluorescence decay of incorporated DPH in liposomal membrane
      after gamma-radiation. The reduction of DPH fluorescence and formation of MDA
      following radiation were significantly affected when alpha-tocopherol was
      incorporated into the liposomes. The observed effects of alpha-tocopherol were
      found to be dependent on its concentration in the liposome. A marked difference
      in emission spectra of DPH was found on radiation of liposomes prepared with the
      probe compared with that obtained from the labeling of liposomes after radiation
      depending on the applied radiation dose. The observed reduction in quantum yield
      of DPH in radiated liposomes is interpreted in terms of its environmental changes
      to a greater polarity. These results suggest that DPH fluorescence may provide an
      index of radiation induced lipid peroxidation caused by free radical reaction in
      unilamellar lecithin liposomes.

PMID- 12186744
TI  - Expression of transcriptional repressor NC2alpha during Xenopus early
      embryogenesis.
AB  - To study the mechanisms behind the suppression of gene expression in the early
      phase of Xenopus development (cleavage stage), we conducted in silico cloning of
      the Xenopus transcriptional repressor NC2alpha. A search of the GenBank EST
      database using human NC2alpha as a probe identified Xenopus mitotic
      phosphoprotein 30 (xMP30) as a prime candidate for Xenopus NC2alpha (xNC2alpha).
      Full-length cDNA sequencing showed that xNC2alpha/xMP30 had a 68.9% identity at
      the amino acid level with its human counterpart. Northern blotting showed that
      xNC2alpha existed abundantly as a maternal mRNA. After the fertilization, the
      expression of xNC2alpha rapidly increased and reached a maximum 3 h before
      midblastula transition (MBT). Then its expression gradually decreased toward the
      early neurula stage. The expression profile of xNC2alpha mRNA is compatible with
      that of xNC2beta, which is the other component of the Xenopus NC2 transcriptional
      repressor.

PMID- 12186745
TI  - Biochemical characteristics of chitinase enzyme from Bacillus sp. of Kamojang
      Crater, Indonesia.
AB  - Chitinase and chitindeacetylase are enzymes capable of degrading chitin into
      chitooligomers and chitosan. The chitinases characterized and purified in this
      study were extracted from the acidophillic Bacillus sp. isolated from Kamojang
      Crater West Java Indonesia. When grown in liquid media containing colloidal
      chitin, the optimum chitinase activity of the acidophilic isolate was reached
      after 4-5 days of incubation. The optimum temperature and pH of the chitinase and
      chitin deacetylase were found at 37 degrees C and pH 5. When incubated at pH 5,
      the activity of chitin deacetylase was increased; after 3 h, the activity was 1.5
      times of the control. The enzyme was stable at pH 4, after 2 h incubation, the
      activity was still 80% of the control. The chitinase and chitin deacetylase
      activities were not influenced by Mg(++) nor Ca(++), Ni(++) and Cu(++) inhibited
      the chitinase activity, while chitin deacetylase activity was not affected by
      Cu(++) addition. When 1 mM of EDTA was added, the enzyme activity was reduced 40
      to 50%.

PMID- 12186746
TI  - Transcription of matR gene in Rhizobium leguminosarum bv. trifolii.
AB  - A transcriptional regulator, MatR, encoded on Rhizobium leguminosarum bv.
      trifolii matR gene was reported to repress mat operon gene expression by binding
      the upstream operator site. Also, MatR activated its own gene expression by
      binding the same site that caused the transcriptional repression of the mat
      operon. This report suggests that MatR plays a dual role in the transcription of
      matR and matABC with malonate as a positive effector.

PMID- 12186747
TI  - Enhancement of circulatory antioxidants by fenugreek during 1,2-dimethylhydrazine
      induced rat colon carcinogenesis.
AB  - We have investigated the modulatory effect of fenugreek seeds (a spice) on
      circulatory lipid peroxidation (LPO) and antioxidant status during 1,2
      dimethylhydrazine (DMH)-induced colon carcinogenesis in male Wistar rats.
      Enhanced LPO in the circulation of tumor bearing animals was accompanied by a
      significant decrease in the levels of ascorbic acid, vitamin E, reduced
      glutathione, glutathione peroxidase, glutathione S-transferase, superoxide
      dismutase and catalase. Inclusion of fenugreek in the diet significantly
      decreased LPO with simultaneous enhancement of circulating antioxidants. We
      report that fenugreek exert its chemopreventive effect by decreasing circulatory
      LPO and enhancing antioxidant levels.

PMID- 12186748
TI  - Expression of human endostatin in larvae of silkworm (Bombyx mori) and in vitro
      activity assays.
AB  - Human endostatin is a novel antiangiogenic molecule, which can inhibit the
      proliferation and development of new blood vessels, and experimentally can cause
      nearly complete regression of established tumors. In this paper, the cDNA
      encoding human endostatin was cloned into a baculovirus shuttle vector pBacPAK8
      and co-infected with linearized Bm-BacPAK6 DNA into and BmN cells. The
      recombinant virus was screened and identified by PCR, DNA and RNA dot
      hybridization, and ELISA assay. The recombinant endostatin was expressed in
      culture cells, and the larvae and pupa of silkworm by inoculation of recombinant
      virus. The biological activity assay showed that the expression product in larvae
      was over 150 microg/ml, about 50-fold higher than that expressed in cultured
      cells. SDS-PAGE and Western blotting analysis showed a pattern of molecular
      weight of about 20 kDa. The bio-activity of the protein product was determined by
      human umbilical vein endothelial cells (ECV304) proliferation test in vitro and
      the chick chorioallantoic membrane (CAM) vascular inhibition test. Endostatin
      showed significant inhibitory effect on endothelial cells in a dose-dependent
      manner. Silkworm-produced endostatin induced apoptosis of endothelial cells and
      also inhibited angiogenesis in the CAM assay. Combination regimen using
      angiostatin and endostatin showed more than additive effect in angiogenic
      inhibition and increasing apoptosis when compared with treatment with the
      individual antiangiogenic protein.

PMID- 12186749
TI  - Alteration in ouabain-sensitive sodium potassium pump of erythrocytes during
      pregnancy induced hypertension: a kinetic study.
AB  - The erythrocytes are widely used as model cells for studies of sodium-potassium
      pump (Na(+)-K(+) pump) in health and disease. Hence, to explore the possible role
      of the Na(+) transport across the cell membrane in the pathogenesis of pregnancy
      induced hypertension (PIH), the present study was conducted to assess the Na(+)
      K(+) pump functions in relation to its intrinsic kinetic properties using
      erythrocytes (RBC). Erythrocyte sodium concentration in pregnancy-induced
      hypertensive women was significantly (p<0.01) lower in comparison to normotensive
      pregnant women. On the contrary erythrocyte potassium was significantly higher
      (p<0.01) in PIH women as compared to normotensive pregnant women. Observed
      alterations in Na(+) and K(+) concentrations in erythrocytes were associated with
      significantly (p<001) increased Ouabain-sensitive sodium efflux rate and rate
      constants in erythrocytes from PIH women. Further, kinetic studies revealed that
      increased Ouabain-sensitive efflux rate constant in RBC from PIH women was
      accompanied by increased maximal velocity (V(max)) of Na(+)-K(+) pump. However,
      the affinity constant (K(m)) was unaltered in both the groups. Therefore, these
      findings suggest that increased Na(+)-K(+) pump activity in RBC of PIH women
      could be due to either increased numbers of Na(+)-K(+) pump units of increased
      numbers of active subunits of Na(+)-K(+) pump possibly due to specific plasma
      factors in PIH women.

PMID- 12186750
TI  - Fractionation of scorpion (Mesobuthus tamulus) venom and the impact of specific
      fractions on glutamate metabolism.
AB  - The fractionation of the venom of Indian red scorpion (Mesobuthus tamulus) was
      performed using CM-52 (carboxy methyl cellulose) ion-exchange chromatography. The
      toxic potential of these fractions were tested on lepidoptera larvae and mice.
      The CM-52 fractions, which showed toxicity were further used to study their
      impact on glutamate metabolism. The glutamate content increased and glutamine
      synthetase and glutamate decarboxylase activity levels were elevated in
      envenomated animals. The present results reveal that glutamine is rapidly
      metabolized to glutamate and gamma-aminiobutyric acid indicating that the pool of
      neurotransmitters is maintained and regulated by glutamine biosynthesis. The
      scorpion neurotoxins inhibit the glutamate dehydrogenase activity, suggesting a
      decreased deamination of glutamate.

PMID- 12186751
TI  - Purification and characterization of aminobutyraldehyde dehydrogenase from
      Arthrobacter Sp. TMP-1.
AB  - Aminobutyraldehyde dehydrogenase was purified to essentially homogeneity from
      putrescine-grown cells of Arthrobacter sp. TMP-1. The molecular weights of the
      enzyme and its subunit were 201,000 and 51,000, respectively, suggesting that the
      enzyme is a tetramer of identical subunits. The apparent Michaelis constants
      (K(m)) for 4-aminobutyraldehyde, 3-aminopropionaldehyde and 4
      guanidinobutyraldehyde were approximately 65, 150, and 85 microM, respectively.
      Linear fatty aldehydes also tested were less active as a substrate, while the
      tested succinate-semialdehyde and branched fatty aldehydes were inert. The enzyme
      utilized both NAD(+) and NADP(+) as coenzymes. The optimum pH was 8.0. The enzyme
      lost 64% of its activity when held at 40 degrees C for 10 min.

PMID- 12186752
TI  - Sulfo-SADP (sulfosuccinimidyl[4-azidophenyldithio]propionate) an active site
      directed reagent inhibiting the NADPH dependent O2- generation of leukocyte
      cytochrome b(558).
AB  - Functional reagents known to bring about the formation of a distinct membrane
      molecular complex of the subunits of cytochrome b(558) (gp 91(phox) and
      p22(phox)) were investigated for their influence on the O2- generating capability
      of liposome incorporated cytochrome b(558) preparations. One,
      ethyleneglycolbis[sulfo-succinimidylsuccinate], (sulfo-EGS) was found to inhibit
      O2- generation at concentrations which are known to result in cross-linking the
      two subunits of cytochrome b(558). Sulfosuccinimidyl [4-azidophenyldithio]
      propionate, (sulfo-SADP) on the other hand, was found to be a powerful inhibitor
      of the cytochrome b(558) dependent O2- production at concentrations not able to
      result in cross linking of the two subunits. Sulfo-SADP inhibits the cytochrome
      b(558) O2- production 50% at 25 microM, while sulfo-EGS requires 400 microM. For
      these reagents, the succinimidyl group of sulfo-SADP and sulfo-EGS is the
      reactive group, which inhibit irreversibly, cytochrome b(558) generation of O2-.
      Both sulfo-SADP and sulfo-EGS have similar linker arms of 13.9 and 16.1 A,
      respectively. The difference, accounting for the strong inhibitory profile for
      sulfo-SADP as compared with sulfo-EGS, resides in the aryl group associated with
      the sulfo-SADP. The aryl group of sulfo-SADP has been found to be important in
      directing the specificity of the probe in its inhibition of O2- generation. When
      the disulfide bond linking the aromatic portion of the probe to the succinimidyl
      ring is cleaved by DTT (dithiothreitol), the product loses its specificity and
      has an inhibitory activity with respect to O2- generation comparable to that of
      sulfo-EGS. The partial protection against the inhibitory influence of sulfo-SADP
      by NADP(+) indicates that the reagent may interact at the pyridine nucleotide
      binding domain of cytochrome b(558). Its low inhibitory titer and its water
      solubility suggest that sulfo-SADP reacts with a specific amine (the primary
      reactant for the succinimidyl group) on cytochrome b(558).

PMID- 12186753
TI  - Characterization of the major tail protein gpP encoded by Lactobacillus plantarum
      phage phi gle.
AB  - Lactobacillus plantarum temperate phage phi g1e encodes a major virion protein
      gpP. In the present study, the gpP protein was overproduced in Escherichia coli
      under plac, and purified. Like the native-gpP protein from phi gle particles
      (Kakikawa et al., 1996), the purified-gpP protein had an apparent molecular mass
      of 26.0 kDa on SDS polyacrylamide gel electrophoresis (PAGE), larger than that
      (18.8 kDa) predicted from the DNA sequence, and was deficient in the first
      methionine as revealed by the N-terminal protein sequencing. In addition,
      analysis by immunoelectron microscopy demonstrated that immunogold particles
      (associated with antigpP-sera) specifically bound to the tails of phi gle
      particles, indicating that gpP is a main tail component (putatively a tube
      protein).

PMID- 12186754
TI  - The cloning of Ty1-copia-like retrotransposons from 10 varieties of banana (Musa
      Sp.).
AB  - Ty1-copia-like retrotransposons have been identified and investigated in several
      plant species. Here, the internal region of the reverse transcriptase (RT) gene
      of Ty1-copia-like retrotransposons was amplified by PCR from total genomic DNA of
      10 varieties of banana. Two to four clones from each variety were sequenced.
      Extreme heterogeneity in the sequences of Ty1-copia-like retrotransposons from
      all the varieties was revealed following sequence analysis of the reverse
      transcriptase (RT) fragments. The size of the individual RT gene fragments varied
      between 213 and 309 bp. Southern blots of genomic DNA digested from Musa
      acuminata and other banana varieties probed with W8 clone from M. acuminata and
      A4 clone from Pisang Abu Nipah showed similar strong, multiple restriction
      fragments together with other faint hybridization band patterns with variable
      intensities indicating the presence of many copies of the Ty1-copia-like
      retrotransposons in the genomes. There was no correlation between retroelement
      sequence and the banana species (with A or B genomes) from which it arose,
      suggesting that the probes are not useful for tracking genomes through breeding
      populations.

PMID- 12186755
TI  - Biophysical behavior of Scomberoides commersonianus skin collagen.
AB  - Some biophysical characteristics of the skin collagen from Scomberoides
      commersonianus were measured and compared to those of rat tail tendon. Stress
      strain data indicate that the strain at break as well as the tensile strength of
      the fish skin without scales increased significantly. The maximum tension in case
      of rat skin is at least a factor of two higher than that observed in fish skin.
      The much lower hydrothermal isometric tension measurements observed in fish skin
      are attributable to a lesser number of heat stable crosslinks. Stress relaxation
      measurements in the fish skin indicate that more than one relaxation process may
      be involved in the stabilization of collagenous matrix. The observed differences
      in the biophysical behavior of fish skin may well arise from combination of
      changes in extent of hydroxylation of proline in collagen synthesis, hydrogen
      bond network and fibril orientation as compared to rat tail tendon.

PMID- 12186756
TI  - Enhanced GABA(B) receptor in neoplastic rat liver: induction of DNA synthesis by
      baclofen in hepatocyte cultures.
AB  - In the present study, the involvement of GABA(B) binding parameters were analyzed
      in partial hepatectomized (PH), lead nitrate (LN) induced hyperplastic and N
      nitrosodiethylamine (NDEA) treated neoplastic rat livers at the peak DNA
      synthesis. The receptor up-regulated significantly in NDEA treated group compared
      with respective control. The affinity of the receptor decreased in PH while it
      increased in LN treated rats. In the other groups, the binding parameters
      remained unaltered. The displacement analysis using GABA(B) receptor agonist,
      [3H]baclofen, against baclofen showed a shift in affinity of the receptor towards
      high-affinity in PH rats and towards low-affinity in LN treated rats. Baclofen
      dose-dependently induced EGF mediated DNA synthesis in primary hepatocyte
      cultures. Also, it significantly reduced the TGFbeta1 suppression of EGF induced
      DNA synthesis. The effect of baclofen on hepatocyte DNA synthesis was abolished
      by the addition of G(i)-protein inhibitor, pertussis toxin, suggesting the
      involvement of GABA(B) receptor mechanisms in hepatocyte DNA synthesis. Baclofen
      alone could not elicit any significant change in DNA synthesis. Thus, our results
      show that GABA(B) receptor enhancement induce hepatic neoplasia. Also, baclofen
      is seen to act as a potent co-mitogen, triggering DNA synthesis in primary
      cultures of rat hepatocytes, mediated through the G(i) protein coupled GABA(B)
      receptors.

PMID- 12186757
TI  - Copper/zinc superoxide dismutases in Dictyostelium discoideum: amino acid
      sequences and expression kinetics.
AB  - Genes for Copper/Zinc superoxide dismutases, designated sodA and sodB, in the
      cellular slime mold Dictyostelium discoideum were analyzed. It was found that
      these gene products contain charged amino acid residues and hydrophobic stretches
      in their N-terminal regions, suggesting that they are extracellular Cu/Zn
      superoxide dismutases. The sodA and sodB are expressed in cells in the growth
      phase and throughout the developmental phases, suggesting that they are the
      housekeeping genes. The sodA is induced by H(2)O(2) exposure but not by UV
      irradiation, whereas sodB is induced both by H(2)O(2) exposure and UV
      irradiation. Such distinct kinetics of the expression patterns suggests that
      these enzymes play unique roles in D. discoideum.

PMID- 12186758
TI  - Gene cluster of nitrous oxide reduction in the deep sea of mariana trench.
AB  - The gene of nitrous oxide reductase (nosZ) and entire region of nos gene cluster
      from Pseudomonas sp. strain MT-1, which is isolated from the sediment of Mariana
      Trench, was identified. Gene organization in nos gene cluster is similar to that
      of other bacteria, and nosZ was highly homologous to nosZ of other Pseudomonads.
      The remarkable property was the existence of a gap from Arg-302 to Ser-309
      (numbered by NosZ of P. aeruginosa), which might be a feature of marine bacterial
      NosZ. It is interesting that nosZ of the strain MT-1 is not related so closely to
      P. stutzeri, although 16S rDNA of the strain MT-1 is highly homologous to that of
      P. stutzeri. The existence of nosZ gene in the strain MT-1 indicated the presence
      of a complete denitrification (nitrate to N(2)) in the Mariana Trench. This is
      the first report on genetic analysis of denitrification in the deep sea.

PMID- 12186759
TI  - Lipid peroxidation and antioxidant status in cervical cancer patients.
AB  - The present study examined the relationship between lipid peroxidation and
      antioxidant status in plasma, erythrocyte and erythrocyte membrane of cervical
      cancer patients and an equal number of age and sex matched normal subjects as
      well as patients with cervicitis. Lipid peroxidation was significantly increased
      with concomitant decrease in antioxidant levels in cervical cancer patients as
      compared to normal subjects and patients with cervicitis. The elevated lipid
      peroxidation and disturbed antioxidant status was also noticed in cervicitis
      patients as compared to normal subjects. This increase in lipid peroxidation can
      be attributed to possible breakdown of antioxidant mechanisms in cervicitis and
      cervical cancer patients.

PMID- 12186760
TI  - Development of a modified method for sequencing high G:C regions in chicken
      anemia virus genome.
AB  - Two areas in the chicken anemia virus (CAV) genome have high G:C content with
      secondary structures. These two G:C rich areas could not be sequenced with Perkin
      Elmer's Big Dye Terminator Cycle Sequencing Kit. Several modifications were
      carried out to solve the problem. Finally, a package of modified method was
      developed to sequence the high G:C areas. The result showed that the Perkin
      Elmer's Big Dye Terminator Cycle Sequencing Kit with the normal procedures are
      not suitable for sequencing the high G:C regions of the CAV genome. The present
      developed method made the Perkin Elmer's Kit useful for the first time to
      sequence the G:C rich hairpin structures of the CAV genome. The system may be
      useful to sequence all other G:C rich DNA templates.

PMID- 12186761
TI  - Base excision repair (BER) and the brain.

PMID- 12186762
TI  - S-methyldithiocarbazate and its Schiff bases: evaluation of bondings and
      biological properties.
AB  - Eight selective nitrogen-sulfur donor ligands have been synthesized from the
      condensation of S-methyldithiocarbazate (SMDTC) with aldehydes and ketones with a
      view to evaluating their antimicrobial and cytotoxic activities, and also to
      correlate the biological properties with the structure of the ligands. The
      compounds were all characterized by elemental analyses and other physicochemical
      techniques. SMDTC and the Schiff bases were screened for antimicrobial and
      cytotoxic activities. SMDTC showed very large inhibition zones (24-44 mm) against
      bacteria and fungi with a minimum inhibitory concentration (MIC) of 390-25,000
      and 1562-6250 microg ml(-1), against different bacteria and fungi, respectively.
      Streptomycin and nystatin were used as the internal standards against bacteria
      and fungi, respectively. SMDTC along with its Schiff bases with pyridine-2
      carboxaldehyde, acetylacetone and 2,3-butanedione were strongly antifungal and
      the MIC values were comparable to nystatin. Most of the Schiff bases were
      strongly cytotoxic. In particular, those with pyridine-2-carboxaldehyde and 2,3
      butanedione have CD(50) values of 5.5, 1.9-2.0 microg ml(-1), respectively,
      against leukemic cells, while against colon cancer cells, the values were 3.7 and
      2.0 microg ml(-1), respectively. The glyoxal Schiff base was strongly active only
      against leukemic cell with CD(50) value of 4.0 microg ml(-1). The present
      findings have been compared with standard drugs.

PMID- 12186763
TI  - Sequence and phylogenetic analysis of the VP2 gene of very virulent infectious
      bursal disease virus isolates.
AB  - Previously we have shown that very virulent infectious bursal disease viruses
      (vvIBDV) that are SspI, TaqI and StyI positive (92/04, 97/61 and 94/B551) but not
      SspI and TaqI positive and StyI negative (94/273) cause high mortality, up to 80%
      in specific-pathogen-free chickens with significant damage of the bursal as well
      as nonbursal tissues. In this study, we sequenced the VP2 gene (1351 bp) of the
      92/04, 94/273 and 94/B551 and compared them with other IBDV strains. All the
      isolates have the unique amino acid residues at positions 222A, 256I, 294I and
      299S found in other vvIBDV strains. The deduced VP2 amino acids encoded by 92/04
      is identical to the vvIBDV strains from Israel (IBDVKS), Japan (OKYM) and Europe
      (UK661), whereas the 94/273 and 94/B551 isolates have one to three amino acid
      substitutions. The 94/273 has two amino acid substitutions at positions 254 G to
      S and at 270 A to E that have not been reported before from vvIBDV strains. The
      94/B551 also has one amino acid substitution at position 300 E to S, which is
      uncommon among other vvIBDV strains. However, phylogenetic analysis suggested
      that the isolates are very close to each other and all of them may have derived
      from the same origin as vvIBDV strains isolated from China, Japan and Europe.
      Even though antigenic index analysis of the 94/273 and 94/B551 indicated that the
      isolates are unique compared to other IBDV strains, their antigenic variation
      remain to be determined by monoclonal antibody study.

PMID- 12186764
TI  - Ca(2+) transport of Ca(2+)-ATPase of the sarcoplasmic reticulum in an ADP
      sensitive phosphoenzyme state.
AB  - To understand the energetics of Ca(2+)-transporting adenosine triphosphatase
      (Ca(2+)-ATPase), it is important to determine the energy consumption step. To do
      this, we measured the dissociation of Ca(2+) from Ca(2+)-ATPase into Ca(2+)
      loaded vesicles. We observed that 45Ca(2+) added to the outside of the vesicles
      accumulated in the 40Ca(2+)-loaded vesicles after the addition of ADP and ATP.
      The acceleration of 45Ca(2+) accumulation increased by 1.4-fold after the
      addition of 1 microM ADP. Under the same conditions, Ca(2+)-dependent phosphate
      liberation was not observed, and all of the active phosphoenzymes were in the ADP
      sensitive phosphoenzyme (E(1)P) state. These results indicated that the ADP
      stimulated 45Ca(2+) accumulation by the ADP-ATP exchange reaction and that this
      ADP-ATP exchange reaction did not pass through the ADP-insensitive phosphoenzyme
      state. Therefore, we demonstrate that one Ca(2+) ion dissociates at the E(1)P
      state, which does not correspond with the phosphoenzyme conversion, that is the
      energy consumption step in the E(1)-E(2) model.

PMID- 12186765
TI  - Disappearance of M(r) 25,000 protein, a new protein kinase substrate, in parallel
      with a kind of serpin during embryogenesis.
AB  - M(r) 25,000 protein (pp25) is a protein kinase substrate detected recently in
      Xenopus laevis oocytes [Hashimoto, E. et al. (1995) J. Biochem. 118, 453-460],
      but the physiological role of this protein remains to be determined. In order to
      elucidate some characteristics of pp25, a polyclonal antibody was raised against
      it and the distribution and quantitative changes of this protein were examined
      using various tissues and biological systems. In Western blot analysis, pp25 was
      detected only in Xenopus oocytes and not in other frog tissues when the heat
      stable cytosolic fraction from each tissue was examined. Although the amount of
      pp25 apparently did not change during oocyte maturation induced by progesterone,
      pp25 disappeared in embryos around Nieuwkoop/Faber stages 45-48 in parallel with
      the change of pNiXa (a kind of serpin). These results suggest that pp25 plays
      some specific role(s) in Xenopus oocytes and that the level of pp25 changes
      dramatically during embryonic development.

PMID- 12186766
TI  - Genomic organization and fine-mapping of the human leucine zipper-bearing kinase
      (LZK) gene.
AB  - Leucine zipper-bearing kinase (LZK) is a new member of the mixed lineage protein
      kinase family. We previously cloned a cDNA encoding LZK from a human cerebellum
      cDNA library. The following studies indicated that LZK serves as a MAPKKK in the
      JNK/SAPK pathway in cells, and a scaffold protein, JIP-1, enhances LZK-induced
      JNK/SAPK pathway activation via physical association. Here we report
      characterization of the gene structure and fine chromosomal mapping of the human
      LZK gene. Polymerase chain-reaction (PCR) studies indicated that the human LZK
      coding sequence is composed of 13 exons, and that all the splice acceptor and
      donor sequences obey the GT-AG rule. Chromosomal localization studies involving
      FISH mapping demonstrated that the human LZK gene is located at 3q27.

PMID- 12186767
TI  - Cloning and expression of the phosphoprotein gene of Newcastle disease virus in
      Escherichia coli.
AB  - The phosphoprotein (P) gene of a heat stable Newcastle disease virus (NDV) was
      cloned, sequenced and expressed in Escherichia coli. SDS-PAGE analysis of the
      recombinant P protein (395 amino acids) and a C-terminal extension derivative
      (424 amino acids), gave rise to two distinct protein bands with molecular masses
      of approximately 53-55 and 56-58 kDa, respectively, which are approximately 26
      30% heavier than those calculated from the deduced amino acid sequences. The
      differences in molecular mass on SDS-PAGE are thought to be attributed to the
      acidic nature of the P protein (pI=6.27) and also the different degrees of
      phosphorylation in the prokaryotic cell. Amino acid sequence comparison of the P
      protein among the published NDV strains showed that they were highly conserved
      particularly at the putative phosphorylation sites.

PMID- 12186769
TI  - Taurine modulates antioxidant potential and controls lipid peroxidation in the
      aorta of high fructose-fed rats.
AB  - High dosage of fructose induces insulin resistance, glucose intolerance and
      alterations in plasma lipid profile in normal rats. Recently, it has been shown
      that these rats also develop oxidative stress, which plays a prominent role in
      diabetic pathology. We now report the effect of taurine on the susceptibility of
      the aorta to lipid peroxidation and also on the activities of enzymic and non
      enzymic antioxidants in rats fed a high fructose-diet for 4 weeks. Fructose-fed
      rats were more susceptible to lipid peroxidation as measured by thiobarbituric
      acid reactivity, and antioxidant status was significantly lower. Taurine
      supplementation caused a significant reduction in the production of
      thiobarbituric acid--reactive substances and significant rises in antioxidant
      enzyme activities. The levels of lipid peroxides, diene conjugates, lipofuscin
      and hydroperoxides were significantly higher in fructose-fed rats. When these
      rats received taurine in drinking water, no peroxidative changes were observed.
      Increased aorta lipid peroxidation could play a role in the pathology associated
      with fructose-feeding, and taurine reduces the lipid peroxidation by inducing
      antioxidant enzymes.

PMID- 12186768
TI  - Molecular characterization and expression of a putative ATPase domain from
      Eimeria tenella.
AB  - VCP (Valosin-Containing Protein), a member of the AAA (ATPases Associated to a
      variety of cellular Activities) family of proteins, possesses a duplicated highly
      conserved ATPase domain. An expressed sequence tag (EST), representing a clone
      from the Eimeria tenella merozoite cDNA library, was found to have high
      similarity to VCP genes from other organisms. A complete sequence derived from
      the corresponding clone (designated eth060) shows amino acid identity of 42-62%
      with other members of the VCP subfamily. Sequence analysis identified a putative
      ATPase domain in the eth060 sequence. This domain was PCR-amplified using gene
      specific primers and cloned into a pBAD/Thio-TOPO expression vector. Expression
      in Escherichia coli demonstrated that the putative ATPase domain, which consists
      of 414 amino acid residues, produced a fusion protein of approximately 60 kDa in
      size.

PMID- 12186770
TI  - Biological implications of genes differentially expressed in human hippocampus
      and spinal cord.
AB  - The hippocampus is involved in learning and memory of intellectual functions
      whereas the spinal cord carries sensory impulses from the trunk and limbs to the
      brain and it returns commands from the brain to the muscles and glands. The
      relative expression levels of genes in human hippocampus and spinal cord were
      determined using high-density cDNA-arrays. Validations by semi-quantitative RT
      PCR, Northern, and Western analyses show good agreement with cDNA-array results.
      Those genes differentially expressed in hippocampus encode proteins that are
      involved either in the neuronal plasticity or learning and memory signaling
      cascades. Interestingly, those differentially expressed in the spinal cord encode
      proteins that are associated with the responses to spinal cord injuries. These
      results also demonstrate the feasibility of comparing a vast number of gene
      expression profiles between various brain regions for potential targets with
      respect to abnormal brain functions.

PMID- 12186771
TI  - Protein denitration/modification by glutathione-S-transferase and glutathione
      peroxidase.
AB  - Peroxynitrite (PN)-pretreated histone III-S (NH) and reduced glutathione (GSH)
      treated NH (NH(GSH)) were incubated with glutathione-S-transferase (GST) and
      glutathione peroxidase (GPX). Western blot analysis revealed decreased 3
      nitrotyrosine immunoreactivity for NH(GSH), but not for NH. Additionally,
      increased nitrate was noted as an end product of these enzymatic reactions. The
      findings imply that GSH-treatment of NH may facilitate its conformational change
      in favor of subsequent enzymatic denitration and/or modification, which could be
      vital in relieving cellular oxidative stress and regulating NO/PN-mediated signal
      transduction cascade.

PMID- 12186772
TI  - Differential conformational environment of tryptophan in epsilon native
      prototoxin and active toxin from Clostridium perfringens type D.
AB  - The tryptophan content of Clostridium perfringens type D epsilon protoxin and
      toxin was found to be one residue per molecule of protein. N-bromosuccinimide in
      the presence of urea cleaves the tryptophan with total loss of lethality in both
      toxin and prototoxin. Fluorescence spectroscopy, circular dichroism (CD) and 10%
      ethylene glycol solvent perturbation studies showed that the tryptophan in
      epsilon toxin and that in prototoxin have different conformational environments.
      The tryptophan is more on the surface in the prototoxin than in the toxin
      molecule. NBS causes total loss of lethality of the toxin with its ellipticity
      coming to almost zero in the near UV region of the CD.

PMID- 12186773
TI  - Extraction of cereal prolamins and their toxicity in coeliac disease.
AB  - Simple extraction of prolamins from cereal flour using 70% aqueous ethanol leads
      to co-extraction of lipids and other secondary products. Treatment of the crude
      extract with an excess of pure ethanol resulted in the removal of the majority of
      these compounds. Prolamin extracts obtained following ethanol precipitation
      showed little difference to products of more complex, multi stage, selective
      extractions, when compared using MALDI-TOF mass spectrometry. Toxicity tests on
      enzymic digests of ethanol-precipitated prolamins from coeliac-toxic cereals,
      coeliac-non-toxic cereals and oats were carried out using a rat liver lysosome
      assay. The prolamins from the ethanol-precipitated extracts showed greater
      activity than those extracted using only 70% ethanol for extraction. As the
      ethanol precipitation method is simple and provides a prolamin extract of
      sufficient purity for further evaluation, this procedure has been adopted as an
      alternative to more tedious procedures for preparation of cereal prolamins.

PMID- 12186775
TI  - Kinetics of inhibition and molecular asymmetry in pigeonpea (Cajanus cajan)
      urease.
AB  - Urease from seeds of pigeonpea showed a time-dependent and irreversible
      inactivation at very low concentrations of heavy metal ions. Concentration of
      Cu(2+), Hg(2+) and Ag(+) required for 50% inactivation, on 10 min of incubation,
      were found to be 2.2 x 10(-6), 2.9 x 10(-8) and 6.3 x 10(-12) M, respectively.
      The kinetics of inactivation with each of these metal ions was found to be
      biphasic, with half of the activity being lost in a fast phase and remaining in a
      slow phase. Acetohydroxamate (AHA) inhibits pigeonpea urease competitively and
      reversibly with a K(i) of 0.041 mM at pH 7.3. This inhibition was found to be pH
      dependent. A reversible and time-dependent inhibition was observed with AHA. AHA
      inhibition revealed biphasic kinetics as observed with the heavy metal ions.
      Pigeonpea urease was also inhibited by fluoride ions competitively with a K(i)
      value of 1.23 mM. These inhibition studies suggest the possible interaction of
      these inhibitors with active site thiol groups and Ni (II) ion. A mechanism has
      been proposed for each of these inhibitors and compared with inhibition studies
      reported for other ureases.

PMID- 12186774
TI  - Hydroxyproline distribution in the plasma of various mammals.
AB  - We have investigated the presence of total, free, protein-bound and peptide-bound
      hydroxyproline (Hyp) in the plasma of different mammals viz., camel, bovine,
      sheep, human, rabbit and rat. Total Hyp was significantly highest in human
      followed by rabbit, rat, bovine, sheep and camel (P<0.001). Free Hyp was
      significantly highest in human followed by rabbit, rat, camel, bovine and sheep
      (P<0.001). However, the protein-bound Hyp content was significantly highest in
      rat followed by bovine, human, camel, rabbit and sheep (P<0.001). Peptide-bound
      Hyp was significantly highest in human plasma followed by sheep and rabbit
      (P<0.001). No peptide-bound Hyp was detected in the plasma of camel, bovine or
      rat. In the human plasma, peptide-bound Hyp constituted 60% of the total plasma
      Hyp, followed by protein-bound Hyp, which was 35% of the total, Hyp and free Hyp,
      which was 15% of the total plasma Hyp. In the sheep plasma peptide-bound Hyp
      constituted about 50% of total Hyp followed by protein-bound (40% of the total
      Hyp) and free Hyp, which formed 10% of total Hyp. In the rabbit plasma protein
      bound Hyp constituted 50% of the total Hyp fraction, followed by peptide-bound
      and free, which constituted about 30 and 20%, respectively, of the total Hyp
      fraction of the plasma. Peptide-bound Hyp formed 92, 84 and 82% of the total
      plasma Hyp in rat, camel and bovine, respectively. Free Hyp constituted about 8%
      of the total plasma Hyp in rat and 18% of total Hyp in bovine and camel,
      respectively. The causes of the significant variations in different collagen
      structure and composition with respect to the different species examined are not
      known, however, these variations may results from differences in turn-over rate
      of Hyp in those species.

PMID- 12186776
TI  - Characterisation and molecular cloning of an erythromycin resistance plasmid of
      Lactococcus lactis isolated from chicken cecum.
AB  - An erythromycin resistance plasmid, pAJ01 was isolated from Loctococcus lactis
      isolate C5 that was isolated from a healthy two-week-old chicken cecum. A 4 kb
      plasmid was transformed into plasmidless L. lactis MG1363 before a restriction
      endonuclease map was constructed. It was then fused with pUC19 to form pAJ02,
      which can replicate in Escherichia coli XLI-Blue as well as L. lactis MG1363. The
      plasmid was stably maintained in Lactococcus for more than 100 generations.

PMID- 12186777
TI  - Protective effects of S-allylcysteine on hepatic glutathione and glutathione
      dependent enzymes during hamster cheek pouch carcinogenesis.
AB  - The effects of S-allylcysteine (SAC) on hepatic lipid peroxidation and
      antioxidant status during 7,12-dimethylbenz[a]anthracene (DMBA)-induced hamster
      buccal pouch carcinogenesis (HBP) were investigated in male Syrian hamsters.
      Enhanced lipid peroxidation in the liver of tumour-bearing animals was
      accompanied by significant decreases in the activities of glutathione peroxidase
      (GPx) and glutathione S-transferase (GST) and a reduction in reduced glutathione
      (GSH) levels. Administration of SAC significantly decreased the formation of
      lipid peroxides and enhanced the levels of antioxidants and detoxifying enzymes.
      We suggest that the elevation of hepatic GSH and GSH-dependent enzymes by SAC may
      play a key role in preventing cancer development in the hamster cheek pouch.

PMID- 12186778
TI  - Mitochondrial factors modulate the activity of endonuclease G, the major nuclease
      of Mammalian mitochondria.
AB  - Endonuclease G (Endo G), a sugar-nonspecific nuclease preferring single-stranded
      DNA (ssDNA), is responsible for major nuclease activity in mitochondria. If the
      enzyme provides an important nicking function for mitochondrial DNA (mtDNA) in
      vivo, then mitochondrial factors likely exist which modulate the enzyme's
      activity and prevent cleavage at single-stranded moieties of mtDNA. In the
      present paper, we report that specific membrane phospholipids, polyamines and
      single-stranded DNA-binding protein (SSB) appear to exert such effects in vitro.
      Phosphatidylcholine and phosphatidylethanolamine, the major constituents of the
      mitochondrial inner membrane, stimulated purified Endo G activity 5- to 10-fold.
      Spermine at 5-100 microM also stimulated activity about 4-fold. However, at more
      than 500 microM, the spermine largely inhibited the degradation of ssDNA and
      duplex DNA. Escherichia coli SSB, which has physicochemical properties analogous
      to those of mitochondrial SSB (mtSSB), markedly inhibited the degradation of
      phiX174 ssDNA by Endo G, indicating the possible involvement of mtSSB in vivo in
      protection of single-stranded regions of mtDNA from nucleolytic attacks.

PMID- 12186779
TI  - Existence of two emm-like "mrp" and "emm" genes in the mga regulon of the
      Streptococcus pyogenes strain ST4547.
AB  - Streptococcus pyogenes ST4547 is an opacity factor negative strain, which has
      been recently reported as a new emm type from Malaysia. Nucleotide sequencing of
      the mga regulon of this strain showed the existence of two emm-like genes. The
      emm gene located upstream of the scpA gene comprises 1305 nucleotides encoding
      the putative precursor M protein of 435 amino acids in length with an M(r) of 49
      kDa. or a predicted mature protein of 394 amino acids with an M(r) of 44.8 kDa.
      Another gene mrpST4547 was located upstream of the emm gene and downstream of the
      mga gene. The sequence of this mrp gene comprises 1167 nucleotides encoding a
      predicted protein of 388 amino acids in length with an M(r) of 42.2 kDa. or a
      predicted mature protein of 347 amino acids with an M(r) of 37.9 kDa. The mga
      regulon of strain ST4547 has a mosaic structure comprising segments, which
      originated from different OF positive and OF negative strains. The sequences
      flanking the hyper-variable and C repeats of the emmST4547 gene showed high
      similarity to corresponding regions in the mga regulon of OF positive strains
      notably M15, M4, M22 and M50. In contrast, the sequence within the hyper-variable
      and C repeat regions of the emmST4547 gene revealed high similarity to equivalent
      regions in the OF negative strains. These data indicates that horizontal transfer
      of emm-like gene could have occurred between OF positive and OF negative strains
      resulting in architectural divergence in the mga regulon.

PMID- 12186780
TI  - Possible involvement of dopaminergic neurotransmitter system in dichlorvos
      induced delayed neurotoxicity.
AB  - The present investigation was carried out to elucidate the possible involvement
      of the dopaminergic neurotransmitter system in the development of dichlorvos
      induced delayed neurotoxicity in the rat and to assess the protective efficacy of
      nimodipine against OPIDN (Organophosphate induced delayed neurotoxicity). Single
      subcutaneous dose of dichlorvos (200 mg/kg body weight) resulted in marked
      changes in the dopaminergic neurotransmitter system in terms of increased levels
      of both dopamine and norepinephrine along with significant increase in the
      activity of both the catecholamine synthesizing enzymes, tyrosine hydroxylase
      (TH) and dopamine-beta-hydroxylase. This increase was accompanied with a
      concomitant decrease in the activity of the major degradative enzyme, monoamine
      oxidase. Scatchard plot analysis revealed a significant decrease in both K(d) and
      B(max) for dopamine D2 receptors. Administration of nimodipine, a centrally
      acting calcium channel blocker, along with dichlorvos restricted all these
      alterations to within control values and could also ameliorate certain
      behavioural deficits by maintaining the dopaminergic neurotransmitter system. The
      study underlines the importance of alterations in the dopamine system as a
      possible causative mechanism behind the behavioural and functional changes
      associated with delayed neurotoxicity.

PMID- 12186781
TI  - The omega-hydroxy palmitic acid induced apoptosis in human lung carcinoma cell
      lines H596 and A549.
AB  - We have found that omega-hydroxy palmitic acid (16-hydroxy palmitic acid, omega
      HPA) has both cell growth inhibiting and cell death inducing actions on human
      lung adenosquamous carcinoma cell line H596 and adenocarcinoma cell line A549.
      Further, these effects were dose- and time-dependent in both cell lines. However,
      in squamous carcinoma cell line H226, omega-HPA had no cytotoxic effect. On the
      other hand, in the human small cell lung carcinoma (SCLC) cell line H128, this
      compound showed weak cytotoxicity. The sensitivity toward omega-HPA was higher in
      H596 cells than in A549 cells. In both H596 and A549 cells, cell growth was
      inhibited to 24.4 and 9.4%, respectively, by treatment with 100 microM omega-HPA
      for 12 h. In the 24 h treatment cells, growth inhibition was increased to 100 and
      38.1%, respectively. In cytotoxicity experiments, the number of dead cells
      increased with incubation times in the presence of omega-HPA: on three days
      incubation with 100 microM omega-HPA, viability was 0 and 13.5%, respectively, in
      H596 and A549 cells. Further, the fragmentation of DNA to oligonucleosomal-sized
      ladder fragments, which is an index of apoptosis, was observed in both cell lines
      on treatment with omega-HPA. Therefore, it is assumed that these cell deaths
      induced by omega-HPA, were apoptosis in these cell lines. Since the number of
      dead cells following treatment with omega-HPA decreased by treatment with omega
      HPA in combination with Z-VAD-fmk, a caspase family inhibitor, it is thought that
      apoptotic cell death was related to caspase activity.

PMID- 12186783
TI  - Cloning, expression and display of the PreS domain of hepatitis B virus on
      filamentous bacteriophage M13.
AB  - The PreS domain of hepatitis B virus (HBV) is believed to be involved in virion
      assembly and attachment to a hepatocyte receptor during infection. In order to
      study the functions of this region, we fused it to the g3p protein of
      bacteriophage M13 that allows the fusion protein to be displayed at the tip of
      the filament. The fusion protein was detected by the anti-E tag antibody on a
      Western blot. The polypeptide in a soluble form was produced by transfecting a
      non-suppressor E. coli host cell with the recombinant phagemid. The soluble
      protein was detected in cytoplasm, in the periplasmic space and also in the
      medium. The functional display of the PreS domain would provide an alternative
      means to study its interactions with the nuleocapsid and hepatocytes.

PMID- 12186782
TI  - Phage display of recombinant antibodies toward Burkholderia pseudomallei
      exotoxin.
AB  - We have used the phagemid pComb3H to construct recombinant phages displaying the
      single chain variable fragment (ScFv) towards exotoxin of Burkholderia
      pseudomallei. Variable heavy and light chain fragments were amplified from the
      hybridoma 6E6A8F3B line, with a wide spectrum of primers specific to mouse
      antibody genes. Through overlapping extension polymerase chain reaction, the
      heavy and light chain fragments were linked to form the ScFv which was
      subsequently cloned into the phage display vector and transformed into ER2537
      cells to yield a complexity of 10(8) clones. The transformants were screened by
      four rounds of biopanning against the exotoxin and resulted in selective
      enrichment of exotoxin-binding antibodies by 301 fold. The phage pool from the
      final round of selection displayed antibodies of high-affinity to the exotoxin as
      demonstrated by ELISA. Several clones were selected randomly from this pool and
      analysed by restriction enzyme digestion, fingerprinting and sequencing.
      Restriction analysis confirmed that all clones carried a 700-800 bp insert whose
      sequences, in general, corresponded to that of mouse IgG. Fingerprinting profiles
      delineated the antibodies into two families with different CDR sequences.

PMID- 12186784
TI  - Changes in the retinal transition dipole moment in bacteriorhodopsin of the
      purple membrane of Halobacterium Salinarium at the so-called PH(rev).
AB  - The chromophore transition dipole moment of light-adapted wild-type
      bacteriorhodopsin (WT-bR) in suspension is evaluated for pH range of 2.8-12.
      Significant variations in the transition dipole moment are observed at the so
      called pH(rev). The results have reported a value of 11 and 8.5 Debye for
      chromophore transition dipole moment of the neutral purple and acid blue form of
      bacteriorhodopsin, respectively. There may be a correlation with the process of
      reversing the direction of the permanent electric dipole moment, due to the
      reversal of the surface charge asymmetry, of the purple membrane to its opposite
      side at that pH(rev).

PMID- 12186785
TI  - Enriched levels of erythropoietin in human umbilical cord blood stimulate
      hematopoietic progenitor cells.
AB  - Human umbilical cord blood (CB) is a recognized source of hematopoietic tissues
      for transplantation, the treatment of malignancies and gene therapy, among other
      potential clinical applications. A rich network of hematopoietic cytokines and
      growth factors possessing stimulatory effects on primitive hematopoietic
      stem/progenitor cells further characterizes fetal CB. To better elucidate these
      complex interactions and properties, we compared the hematopoietic activities of
      CB and normal human peripheral blood (PB), by examining growth/survival of normal
      hematopoietic progenitors and erythropoietin-dependent UT-7/EPO cells. Colony
      forming activity assays of normal bone marrow (BM) BFU-E and CFU-GM showed that
      CB significantly enhanced progenitor cell growth in comparison to PB. Apoptosis
      was determined by enumerating APO 2.7 mAb stained cells using flow cytometry. UT
      7/EPO cell cultures subjected to PB exhibited a four-fold higher rate of
      apoptosis than CB exposed cultures, indicating that CB markedly suppressed
      apoptosis in this human leukemic cell line. Immunoprecipitation of UT-7/EPO cell
      lysates and immunodetection of the anti-phosphotyrosine Ab (4G10), revealed that
      CB induced tyrosine phosphorylation of three proteins, with approximate molecular
      masses of 160, 117.5 and 80 kDa. The 80 kDa protein corresponds to the previously
      reported molecular mass for the Epo receptor, suggesting that erythropoietin is
      enriched in CB compared with adult PB.

PMID- 12186787
TI  - Air pollution: an insidious and pervasive component of cardiac risk.

PMID- 12186788
TI  - Cardiovascular disease and insulin-like growth factor I.

PMID- 12186789
TI  - Platelet-derived CD40L: the switch-hitting player of cardiovascular disease.

PMID- 12186790
TI  - Clinical and pathophysiological implications of a bicuspid aortic valve.

PMID- 12186791
TI  - Smoking is associated with altered endothelial-derived fibrinolytic and
      antithrombotic factors: an in vitro demonstration.
AB  - BACKGROUND: Data about the effects of smoking on thrombo-hemostatic factors
      (tissue factor [TF] and tissue factor pathway inhibitor [TFPI-1]) are limited and
      on fibrinolytic factors (tissue plasminogen activator [t-PA] and plasminogen
      activator inhibitor-1 [PAI-1]) are debatable. The present study investigated the
      smoking-related, endothelial cell (EC)-specific responses for these factors and
      their relation to nitric oxide (NO) production in vitro. METHODS AND RESULTS:
      Serum from 8 nonsmokers and 15 smokers were incubated with confluent
      (approximately 85%) human umbilical vein endothelial cells (HUVECs) in 24-well
      tissue-culture plates for 12 hours. After the incubation, basal NO, t-PA, PAI-1,
      TF, TFPI-1 production, and substance P (SP)-stimulated NO, t-PA, and PAI-1
      production were determined. HUVECs treated with smokers' serum showed lower basal
      (P<0.02) and SP-stimulated (P=0.059) t-PA production but similar basal and
      stimulated PAI-1 production (P=0.9 and P=0.6) compared with nonsmokers. Basal t
      PA/PAI-1 molar ratio was significantly reduced in smokers (P<0.005). TFPI-1 level
      in the cell culture supernatant was also significantly lower in smokers compared
      with the nonsmoker group (P<0.05) with no difference in TF level between both
      groups (P=0.5). As previously reported, both basal (P<0.001) and SP-stimulated
      (P<0.05) NO production were significantly reduced in smokers. Basal TFPI-1 in
      culture correlated positively with basal NO production (r=0.42, P=0.04) and
      negatively with serum cotinine level (r=-0.6, P=0.01). CONCLUSIONS: These results
      indicate that cigarette smoking is associated with alterations in EC-derived
      fibrinolytic (t-PA) and antithrombotic (TFPI-1) factors. To our knowledge, this
      is the first demonstration that EC-derived TFPI is affected by smoking and
      endogenous NO or that the degree of smoke exposure may influence TFPI levels in
      an EC milieu.

PMID- 12186792
TI  - Angiotensin II-induced cardiac hypertrophy and hypertension are attenuated by
      epidermal growth factor receptor antisense.
AB  - BACKGROUND: Angiotensin II (Ang II) is a vasoconstrictor but also a growth
      factor. However, the Ang II type 1 receptor does not have a tyrosine kinase
      domain that mediates the cellular signals for mitosis. We have shown that Ang II
      acts via "trans"-activation of the epidermal growth factor receptor (EGFR) to
      induce activation of tyrosine kinase and mitogen-activated protein
      kinase/extracellular signal-regulated kinase (ERK) in vascular smooth muscle
      cells (VSMCs). To examine whether EGFR is involved in the development of left
      ventricular hypertrophy (LVH), we inhibited EGFR with a specific antisense
      oligodeoxynucleotide to attenuate the Ang II-induced cardiovascular hypertrophic
      effects. METHODS AND RESULTS: The antisense oligodeoxynucleotide to EGFR (EGFR
      AS) was designed and tested on Ang II-induced ERK activation in cultured VSMCs.
      We also investigated the effects of EGFR-AS on LVH and blood pressure (BP) in Ang
      II-infused hypertensive rats. In VSMCs, EGFR-AS (2.5 micromol/L) reduced EGFR
      expression and inhibited the Ang II-induced phosphorylation of ERK. In rats, Ang
      II (150 ng/h for 14 days) increased BP compared with controls (184+/-6 mm Hg
      versus 122+/-3 mm Hg; n=7; P<0.01). Continuous intravenous infusion of EGFR-AS (2
      mg/kg) decreased BP (169+/-8 mm Hg; n=8; P<0.05). Ang II infusion increased the
      left ventricular/body weight (LV/BW) ratio compared with control rats (2.75+/
      0.08 versus 2.33+/-0.07; P<0.01). EGFR-AS, but not EGFR-sense, normalized the
      LV/BW in Ang II-infused rats (2.32+/-0.06; P<0.01) and attenuated Ang II-enhanced
      EGFR expression and ERK phosphorylation. CONCLUSION: Ang II requires EGFR to
      mediate ERK activation in VSMCs and the heart. EGFR plays a critical role in the
      LVH induced by Ang II.

PMID- 12186793
TI  - A self-fulfilling prophecy: C-reactive protein attenuates nitric oxide production
      and inhibits angiogenesis.
AB  - BACKGROUND: Given the central importance of nitric oxide (NO) in the development
      and clinical course of cardiovascular diseases, we sought to determine whether
      the powerful predictive value of C-reactive protein (CRP) might be explained
      through an effect on NO production. METHODS AND RESULTS: Endothelial cells (ECs)
      were incubated with recombinant CRP (0 to 100 microg/mL, 24 hours), and NO and
      cyclic guanosine monophosphate (cGMP) production was assessed. The effects of CRP
      on endothelial NO synthase (eNOS) protein, mRNA expression, and mRNA stability
      were also examined. In a separate study, the effects of CRP (25 microg/mL) on EC
      cell survival, apoptosis, and in vitro angiogenesis were evaluated. Incubation of
      ECs with CRP resulted in a significant inhibition of basal and stimulated NO
      release, with concomitant reductions in cGMP production. CRP caused a marked
      downregulation of eNOS mRNA and protein expression. Actinomycin D studies
      suggested that eNOS downregulation was related to decreased mRNA stability. In
      conjunction with a decrease in NO production, CRP inhibited both basal and
      vascular endothelial growth factor-stimulated angiogenesis as assessed by EC
      migration and capillary-like tube formation. CRP did not induce EC survival but
      did, however, promote apoptosis in a NO-dependent fashion. CONCLUSIONS: CRP, at
      concentrations known to predict adverse vascular events, directly quenches the
      production of the NO, in part, through posttranscriptional effect on eNOS mRNA
      stability. Diminished NO bioactivity, in turn, inhibits angiogenesis, an
      important compensatory mechanism in chronic ischemia. Through decreasing NO
      synthesis, CRP may facilitate the development of diverse cardiovascular diseases.
      Risk reduction strategies designed to lower plasma CRP may be effective by
      improving NO bioavailability.

PMID- 12186794
TI  - Comparison of omapatrilat and enalapril in patients with chronic heart failure:
      the Omapatrilat Versus Enalapril Randomized Trial of Utility in Reducing Events
      (OVERTURE).
AB  - BACKGROUND: Combined inhibition of the angiotensin-converting enzyme (ACE) and
      neutral endopeptidase (NEP) may produce greater benefits in heart failure than
      ACE inhibition alone. METHODS AND RESULTS: We randomly assigned 5770 patients
      with New York Heart Association class II to IV heart failure to double-blind
      treatment with either the ACE inhibitor enalapril (10 mg BID, n=2884) or to the
      ACE-NEP inhibitor omapatrilat (40 mg once daily, n=2886) for a mean of 14.5
      months. The primary end point-the combined risk of death or hospitalization for
      heart failure requiring intravenous treatment--was used prospectively to test
      both a superiority and noninferiority hypothesis (based on the effect of
      enalapril in the Studies of Left Ventricular Dysfunction [SOLVD] Treatment
      Trial). A primary end point was achieved in 973 patients in the enalapril group
      and in 914 patients in the omapatrilat group (hazard ratio 0.94; 95% CI: 0.86 to
      1.03, P=0.187)--a result that fulfilled prespecified criteria for noninferiority
      but not for superiority. The omapatrilat group also had a 9% lower risk of
      cardiovascular death or hospitalization (P=0.024) and a 6% lower risk of death
      (P=0.339). Post hoc analysis of the primary end point with the definition used in
      the SOLVD Treatment Trial (which included all hospitalizations for heart failure)
      showed an 11% lower risk in patients treated with omapatrilat (nominal P=0.012).
      CONCLUSION: Omapatrilat reduces the risk of death and hospitalization in chronic
      heart failure but was not more effective than ACE inhibition alone in reducing
      the risk of a primary clinical event. Between-group differences in favor of
      omapatrilat observed in secondary and post hoc analyses warrant further study.

PMID- 12186795
TI  - Elevated levels of oxidative DNA damage and DNA repair enzymes in human
      atherosclerotic plaques.
AB  - BACKGROUND: The formation of reactive oxygen species is a critical event in
      atherosclerosis because it promotes cell proliferation, hypertrophy, growth
      arrest, and/or apoptosis and oxidation of LDL. In the present study, we
      investigated whether reactive oxygen species-induced oxidative damage to DNA
      occurs in human atherosclerotic plaques and whether this is accompanied by the
      upregulation of DNA repair mechanisms. METHODS AND RESULTS: We observed increased
      immunoreactivity against the oxidative DNA damage marker 7,8-dihydro-8-oxo-2'
      deoxyguanosine (8-oxo-dG) in plaques of the carotid artery compared with the
      adjacent inner media and nonatherosclerotic mammary arteries. Strong 8-oxo-dG
      immunoreactivity was found in all cell types of the plaque including macrophages,
      smooth muscle cells, and endothelial cells. As shown by competitive ELISA,
      carotid plaques contained 160+/-29 8-oxo-dG residues/10(5) dG versus 3+/-1 8-oxo
      dG residues/10(5) dG in mammary arteries. Single-cell gel electrophoresis showed
      elevated levels of DNA strand breaks in the plaque. The overall number of
      apoptotic nuclei was low (1% to 2%) and did not correlate with the amount of 8
      oxo-dG immunoreactive cells (>90%). This suggests that initial damage to DNA
      occurs at a sublethal level. Several DNA repair systems that are involved in base
      excision repair (redox factor/AP endonuclease [Ref 1] and poly(ADP-ribose)
      polymerase 1 [PARP-1]) or nonspecific repair pathways (p53, DNA-dependent protein
      kinase) were upregulated, as shown by Western blotting and immunohistochemistry.
      Overexpression of DNA repair enzymes was associated with elevated levels of
      proliferating cell nuclear antigen. CONCLUSIONS: Our findings provide evidence
      that oxidative DNA damage and repair increase significantly in human
      atherosclerotic plaques.

PMID- 12186796
TI  - Particulate air pollution and risk of ST-segment depression during repeated
      submaximal exercise tests among subjects with coronary heart disease: the
      Exposure and Risk Assessment for Fine and Ultrafine Particles in Ambient Air
      (ULTRA) study.
AB  - BACKGROUND: Daily variations in ambient particulate air pollution have been
      associated with cardiovascular mortality and morbidity. We therefore assessed the
      associations between levels of the 3 main modes of urban aerosol distribution and
      the occurrence of ST-segment depressions during repeated exercise tests. METHODS
      AND RESULTS: Repeated biweekly submaximal exercise tests were performed during 6
      months among adult subjects with stable coronary heart disease in Helsinki,
      Finland. Seventy-two exercise-induced ST-segment depressions >0.1 mV occurred
      during 342 exercise tests among 45 subjects. Simultaneously, particle mass <2.5
      microm (PM2.5) and the number concentrations of ultrafine particles (particle
      diameter 10 to 100 nm [NC(0.01-0.1)]) and accumulation mode particles (100 to
      1000 nm [NC(0.1-1)]) were monitored at a central site. Levels of particulate air
      pollution 2 days before the clinic visit were significantly associated with
      increased risk of ST-segment depression during exercise test. The association was
      most consistent for measures of particles reflecting accumulation mode particles
      (odds ratio 3.29; 95% CI, 1.57 to 6.92 for NC(0.1-1) and 2.84; 95% CI, 1.42 to
      5.66 for PM2.5), but ultrafine particles also had an effect (odds ratio 3.14; 95%
      CI, 1.56 to 6.32), which was independent of PM2.5. Also, gaseous pollutants NO2
      and CO were associated with an increased risk for ST-segment depressions. No
      consistent association was observed for coarse particles. The associations tended
      to be stronger among subjects who did not use beta-blockers. CONCLUSIONS: The
      present results suggest that the effect of particulate air pollution on
      cardiovascular morbidity is at least partly mediated through increased
      susceptibility to myocardial ischemia.

PMID- 12186797
TI  - Low serum insulin-like growth factor I is associated with increased risk of
      ischemic heart disease: a population-based case-control study.
AB  - BACKGROUND: Insulin-like growth factor I (IGF-I) has been suggested to be
      involved in the pathogenesis of atherosclerosis. We hypothesize that low IGF-I
      and high IGFBP-3 levels might be associated with increased risk of ischemic heart
      disease (IHD). METHODS AND RESULTS: We conducted a nested case-control study
      within a large prospective study on cardiovascular epidemiology (DAN-MONICA). We
      measured IGF-I and IGFBP-3 in serum from 231 individuals who had a diagnosis of
      IHD 7.63 years after blood sampling and among 374 control subjects matched for
      age, sex, and calendar time. At baseline when all individuals were free of
      disease, subjects in the low IGF-I quartile had significantly higher risk of IHD
      during the 15-year follow-up period, with a relative risk (RR) of 1.94 (95% CI,
      1.03 to 3.66) of IHD compared with the high IGF-I quartile group, when IGFBP-3,
      body mass index, smoking, menopause, diabetes, and use of antihypertensives were
      controlled for. Conversely, individuals in the high IGFBP-3 quartile group had an
      adjusted RR of 2.16 (95% CI, 1.18 to 3.95) of having IHD. Identification of a
      high-risk population with low IGF-I and high IGFBP-3 levels resulted in markedly
      higher risk of IHD (RR 4.07; 95% CI, 1.48 to 11.22) compared with the index
      group. CONCLUSIONS: Individuals without IHD but with low circulating IGF-I levels
      and high IGFBP-3 levels have significantly increased risk of developing IHD
      during a 15-year follow-up period. Our findings suggest that IGF-I may be
      involved in the pathogenesis of IHD.

PMID- 12186798
TI  - Exercise-induced increase in baroreflex sensitivity predicts improved prognosis
      after myocardial infarction.
AB  - BACKGROUND: Despite the rational expectation for a survival benefit produced by
      exercise training among post-myocardial infarction (MI) patients, direct evidence
      remains elusive. Clinically, changes in autonomic balance toward lower vagal
      activity have consistently been associated with increased mortality risk;
      conversely, among both control and post-MI dogs, exercise training improved vagal
      reflexes and prevented sudden death. Accordingly, we tested the hypothesis that
      exercise training, if accompanied by a shift toward increased vagal activity of
      an autonomic marker such as baroreflex sensitivity (BRS), could reduce mortality
      in post-MI patients. METHODS AND RESULTS: Ninety-five consecutive male patients
      surviving a first uncomplicated MI were randomly assigned to a 4-week endurance
      training period or to no training. Age (51+/-8 versus 52+/-8 years), site of MI
      (anterior 41% versus 43%), left ventricular ejection fraction (52+/-13 versus
      51+/-14%), and BRS (7.9+/-5.4 versus 7.9+/-3.4 ms/mm Hg) did not differ between
      the two groups. After 4 weeks, BRS improved by 26% (P=0.04) in trained patients,
      whereas it did not change in nontrained patients. During a 10-year follow-up,
      cardiac mortality among the 16 trained patients who had an exercise-induced
      increase in BRS >or = 3 ms/mm Hg (responders) was strikingly lower compared with
      that of the trained patients without such a BRS increase (nonresponders) and that
      of the nontrained patients (0 of 16 versus 18 of 79 [23%], P=0.04). Cardiac
      mortality was also lower among responders irrespective of training (4% versus
      24%, P=0.04). CONCLUSIONS: Post-MI exercise training can favorably modify long
      term survival, provided that it is associated with a clear shift of the autonomic
      balance toward an increase in vagal activity.

PMID- 12186799
TI  - Microvascular structural correlates of myocardial contrast echocardiography in
      patients with coronary artery disease and left ventricular dysfunction:
      implications for the assessment of myocardial hibernation.
AB  - BACKGROUND: Myocardial contrast echocardiography (MCE) has been used to evaluate
      myocardial viability. There are no data, however, on the pathological
      determinants of myocardial perfusion by MCE in humans and the implications of
      such determinants. METHODS AND RESULTS: MCE was performed in 20 patients with
      coronary artery disease and ventricular dysfunction within 24 hours before
      myocardial biopsy at surgery using a continuous Optison infusion (12 to 16 cc/h),
      with intermittent pulse inversion harmonics and incremental triggering. Peak
      myocardial contrast intensity (MCI) and the rate of increase in MCI (beta) were
      quantitated. Thirty-six transmural myocardial biopsies (2 per patient) were
      obtained by transesophageal echocardiography. Total microvascular (<100 microm)
      density, capillary density and area, arteriolar and venular density, and percent
      collagen content were quantitated with immunohistochemistry. Peak MCI correlated
      with microvascular density (r=0.59, P<0.001) and capillary area (r=0.64, P<0.001)
      and inversely correlated with percent collagen content (r=-0.45, P=<0.01). The
      best relation was observed when the ratio of peak MCI in the 2 biopsied segments
      in each patient was compared with the ratio of microvascular density and
      capillary area (r=0.84 and 0.87, respectively; P<0.001). A significant overlap in
      microvascular density was seen between segments with and without recovery of
      function. The new MCE indices of blood velocity (beta) and flow (peak MCIxbeta)
      better identified recovery of function compared with microvascular density and
      the sole use of peak MCI. CONCLUSIONS: Microvascular integrity is a significant
      determinant of maximal MCI in humans. MCE indices of blood velocity and flow are
      important parameters that predict recovery of function after revascularization.

PMID- 12186800
TI  - Assessing myocardial viability and infarct transmurality with left ventricular
      electromechanical mapping in patients with stable coronary artery disease:
      validation by delayed-enhancement magnetic resonance imaging.
AB  - BACKGROUND: This study was designed to define myocardial viability and establish
      practical cut-off values for differentiating normal myocardial tissue from
      subendocardial and transmural scar tissue by using electromechanical mapping
      (EMM). We validated our results by delayed-enhancement cardiac MRI (DE-MRI).
      METHODS AND RESULTS: We prospectively studied 15 ambulatory patients with stable
      coronary disease who were candidates for cardiac catheterization. Within 48 hours
      of EMM, DE-MRI was performed. Using EMM software, we created a bull's eye
      precisely matched to that generated by DE-MRI. Segment by segment, we compared
      the MRI results to the corresponding unipolar voltage value for that same segment
      in the EMM bull's eye. Of 300 total segments, 275 were compared. The segments
      were divided into normal (n=211), subendocardial scar (n=49), and transmural scar
      (n=15). We found that subendocardial (6.8+/-2.9 mV) and transmural (4.6+/-1.9 mV)
      scar segments had significantly less unipolar voltage than normal (11.6+/-4.5 mV)
      segments (P<0.05 for each comparison). When normal myocardium was compared with
      myocardium with subendocardial scar, the threshold for differentiating between
      the two areas was 7.9 mV (sensitivity, 80%; specificity, 80%). Comparison of
      normal tissue to transmural scar yielded a threshold of 6.9 mV (sensitivity, 93%;
      specificity, 88%). CONCLUSIONS: Our results demonstrate that normal myocardium
      can be accurately distinguished from myocardium with subendocardial or transmural
      infarcts on the basis of unipolar voltage values obtained through EMM. This is
      the first study to validate these results by using cardiac DE-MRI in humans.

PMID- 12186801
TI  - Mapping and ablation of idiopathic ventricular fibrillation.
AB  - BACKGROUND: Ventricular fibrillation is the main mechanism of sudden cardiac
      death. The feasibility of eliminating recurrent episodes by catheter ablation has
      not been reported. METHODS AND RESULTS: Twenty-seven patients without known heart
      disease (13 men, 14 women, 41+/-14 years of age) were studied after being
      resuscitated from recurrent (10+/-12) episodes of primary idiopathic ventricular
      fibrillation; 23 had received a defibrillator. The first initiating beat of
      ventricular fibrillation had an identical electrocardiographic morphology and
      coupling interval (297+/-41 ms) to preceding isolated premature beats typically
      noted in the aftermath of resuscitation. These triggers were localized by mapping
      the earliest electrical activity and ablated by local radiofrequency delivery.
      Outcome was assessed by Holter and defibrillator memory interrogation. Premature
      beats were elicited from the Purkinje conducting system in 23 patients: from the
      left ventricular septum in 10, from the anterior right ventricle in 9, and from
      both in 4. The interval from the Purkinje potential to the following myocardial
      activation varied from 10 to 150 ms during premature beat but was 11+/-5 ms
      during sinus rhythm, indicating location at peripheral Purkinje arborization. The
      premature beats originated from the right ventricular outflow tract muscle in 4
      patients. The accuracy of mapping was confirmed by acute elimination of premature
      beats during local radiofrequency delivery. During a follow-up of 24+/-28 months,
      24 patients (89%) had no recurrence of ventricular fibrillation without drug.
      CONCLUSIONS: Primary idiopathic ventricular fibrillation is a syndrome
      characterized by dominant triggers from the distal Purkinje system. These sources
      can be eliminated by focal energy delivery.

PMID- 12186802
TI  - Ultrasonic characterization of the pulmonary venous wall: echographic and
      histological correlation.
AB  - BACKGROUND: Pulmonary vein isolation with radiofrequency catheter ablation
      techniques is used to prevent recurrences of human atrial fibrillation.
      Visualization of the architecture at the venoatrial junction could be crucial for
      these ablative techniques. Our study assesses the potential for intravascular
      ultrasound to provide this information. METHODS AND RESULTS: We retrieved 32
      pulmonary veins from 8 patients dying from noncardiac causes. We obtained cross
      sectional intravascular ultrasound (IVUS) images with a 3.2F, 30-MHz ultrasound
      catheter at intervals on each vein. Histological cross-sections at the intervals
      allowed comparisons with ultrasonic images. The pulmonary venous wall at the
      venoatrial junction revealed a 3-layered ultrasonic pattern. The inner echogenic
      layer represents both endothelium and connective tissue of the media (mean
      maximal thickness, 1.4+/-0.3 mm). The middle hypoechogenic stratum corresponds to
      the sleeves of left atrial myocardium surrounding the external aspect of the
      venous media. This layer was thickest at the venoatrial junction (mean maximal
      thickness, 2.6+/-0.8 mm) and decreased toward the lung hilum. The outer echodense
      layer corresponds to fibro-fatty adventitial tissue (mean maximal thickness,
      2.15+/-0.36 mm). We found a close agreement among the IVUS and histological
      measurements for maximal luminal diameter (mean difference, -0.12+/-1.3 mm) and
      maximal muscular thickness (mean difference, 0.17+/-0.13 mm) using the Bland and
      Altman method. CONCLUSIONS: Our experimental study demonstrates for the first
      time that IVUS images of the pulmonary veins can provide information on the
      distal limits and thickness of the myocardial sleeves and can be a valuable tool
      to help accurate targeting during ablative procedures.

PMID- 12186803
TI  - Prognostic implications of abnormalities in renal function in patients with acute
      coronary syndromes.
AB  - BACKGROUND: Outcomes in patients with mild to moderate renal function (RF)
      abnormalities presenting with acute coronary syndromes (ACS) are not well
      defined. METHODS AND RESULTS: A convenience sample of 4 ACS trial databases
      including all enrolled patients was assessed to determine 30- and 180-day
      outcomes. The 4 trials were Global Use of Strategies to Open Occluded Coronary
      Arteries (GUSTO) IIb, GUSTO-III, Platelet Glycoprotein IIb/IIIa in Unstable
      Angina: Receptor Suppression Using Integrilin Therapy (PURSUIT), and Platelet
      IIb/IIIa Antagonism for the Reduction of Acute coronary syndrome events in a
      Global Organization Network (PARAGON-A). Patients were stratified into ST-segment
      elevation (STE) and non-ST-segment elevation (NSE) groups and by the presence or
      absence of abnormal RF (creatinine clearance <70 mL/min). In the STE group, 7670
      of 18 621 patients (41%) had abnormal RF. In the NSE group, 8152 of 19 304 (42%)
      had abnormal RF. Patients with abnormal RF were older, more often female, and
      more likely to have adverse baseline characteristics. They had higher mortality
      and higher mortality/nonfatal myocardial infarction (MI) at both 30 and 180 days,
      regardless of ST-segment status. Creatinine clearance was independently
      associated with risk of mortality (hazard ratio 0.79 in the STE group and 0.81 in
      the NSE group) and with risk of mortality/MI (hazard ratio 0.93) in the NSE group
      at 180 days. CONCLUSIONS: Patients presenting with ACS frequently have abnormal
      RF. Abnormal RF is a marker of adverse baseline clinical characteristics and is
      independently associated with increased risk of death and death/MI.

PMID- 12186804
TI  - CD40 ligand inhibits endothelial cell migration by increasing production of
      endothelial reactive oxygen species.
AB  - BACKGROUND: The CD40/CD40 ligand system is involved in atherogenesis. Activated T
      lymphocytes and platelets, which express high amounts of CD40 ligand (CD40L) on
      their surface, contribute significantly to plaque instability with ensuing
      thrombus formation, leading to acute coronary syndromes. Because
      reendothelialization may play a pivotal role for plaque stabilization, we
      investigated a potential role of CD40L on endothelial cell (EC) migration.
      METHODS AND RESULTS: Stimulation of ECs with recombinant CD40L prevented vascular
      endothelial growth factor (VEGF)-induced EC migration, as determined by a
      "scratched wound assay." In addition, activated T lymphocytes and platelets
      significantly inhibited VEGF-induced EC migration and tube formation in vitro.
      Because the activation of endothelial nitric oxide (NO) synthase and the release
      of NO are required for EC migration and angiogenesis, we analyzed the effect of
      NO. Coincubation with the NO donor S-nitroso-N-acetyl-penicillamine (SNAP) did
      not reverse the inhibitory effect of CD40L on VEGF-induced EC migration and tube
      formation. In addition, EC migration induced by SNAP was completely inhibited by
      CD40L. CD40L, however, induced the production of reactive oxygen species and
      reduced endothelial NO bioavailability. This reactive oxygen species-dependent
      effect of CD40L stimulation was reversed with vitamin C or N-acetylcysteine.
      CONCLUSIONS: The activation of the CD40 receptor inhibits EC migration by
      increasing reactive oxygen species. The blockade of EC migration by CD40L may
      critically affect endothelial regeneration after plaque erosion and thereby may
      contribute to the increased risk for development of acute coronary events in
      patients with high circulating levels of CD40L.

PMID- 12186805
TI  - Impaired nitric oxide synthase pathway in diabetes mellitus: role of asymmetric
      dimethylarginine and dimethylarginine dimethylaminohydrolase.
AB  - BACKGROUND: An endogenous inhibitor of nitric oxide synthase, asymmetric
      dimethylarginine (ADMA), is elevated in patients with type 2 diabetes mellitus
      (DM). This study explored the mechanisms by which ADMA becomes elevated in DM.
      METHODS AND RESULTS: Male Sprague-Dawley rats were fed normal chow or high-fat
      diet (n=5 in each) with moderate streptozotocin injection to induce type 2 DM.
      Plasma ADMA was elevated in diabetic rats (1.33+/-0.31 versus 0.48+/-0.08
      micromol/L; P<0.05). The activity, but not the expression, of dimethylarginine
      dimethylaminohydrolase (DDAH) was reduced in diabetic rats and negatively
      correlated with their plasma ADMA levels (P<0.05). DDAH activity was
      significantly reduced in vascular smooth muscle cells and human endothelial cells
      (HMEC-1) exposed to high glucose (25.5 mmol/L). The impairment of DDAH activity
      in vascular cells was associated with an accumulation of ADMA and a reduction in
      generation of cGMP. In human endothelial cells, coincubation with the antioxidant
      polyethylene glycol-conjugated superoxide dismutase (22 U/mL) reversed the
      effects of the high-glucose condition on DDAH activity, ADMA accumulation, and
      cGMP synthesis. CONCLUSIONS: A glucose-induced impairment of DDAH causes ADMA
      accumulation and may contribute to endothelial vasodilator dysfunction in DM.

PMID- 12186806
TI  - Prevention of diabetes-induced microangiopathy by human tissue kallikrein gene
      transfer.
AB  - BACKGROUND: Microvascular insufficiency represents a major cause of end-organ
      failure among diabetics. METHODS AND RESULTS: In streptozotocin-induced diabetic
      mice, we evaluated the potential of human tissue kallikrein (hTK) gene as a sole
      therapy against peripheral microangiopathy. Local delivery of hTK gene halted the
      progression of microvascular rarefaction in hindlimb skeletal muscle by
      inhibiting apoptosis, thus ensuring an improved hemodynamic recovery in case of
      supervening vascular occlusion. The curative action of hTK did not necessitate
      insulin supplementation. Application of gene therapy at a stage of established
      microangiopathy stimulated vascular regeneration. CONCLUSIONS: Our studies
      indicate that hTK may represent a useful tool for the treatment of microvascular
      complications in diabetics.

PMID- 12186807
TI  - Stent-based approach for ventricle-to-coronary artery bypass.
AB  - BACKGROUND: Ventricle-to-coronary artery bypass (VCAB) is an experimental
      revascularization procedure that provides predominantly systolic instead of
      diastolic blood flow to a coronary artery. METHODS AND RESULTS: In a pig model, a
      stent-based procedure (VSTENT) was developed to create a VCAB. After thoracotomy,
      a covered VSTENT was implanted between the left ventricle and the left anterior
      descending coronary artery (LAD). Distal LAD flow, regional myocardial function,
      and intracoronary pressures were determined at different degrees of LAD stenosis
      and during complete LAD occlusion. During 3 hours of LAD occlusion, VSTENT
      preserved net forward flow at 70+/-6% and regional myocardial function at 71+/-8%
      of baseline. Preservation of net flow was influenced by the positioning of the
      VSTENT, with higher preservation also under conditions of increased oxygen demand
      if a "valve-like mechanism" was present during diastole. At a hemodynamically
      relevant level of LAD stenosis (>70%), systolic inflow was predominant after
      VSTENT implantation. Changes in mean diastolic intracoronary pressure that
      resulted from different degrees of LAD stenosis were linearly correlated to net
      flow after VSTENT implantation (r=0.88; P<0.001). CONCLUSIONS: VSTENT for
      ventricle-to-coronary artery bypass was feasible and preserved 70+/-6% of
      baseline flow during complete LAD occlusion. The degree of preservation was
      dependent on the position of the VSTENT creating a valve-like mechanism during
      diastole. Residual diastolic blood flow through a high-grade LAD stenosis
      influenced net flow favorably, because diastolic backflow decreased with
      increasing mean diastolic intracoronary pressure.

PMID- 12186808
TI  - Intramural virtual electrodes during defibrillation shocks in left ventricular
      wall assessed by optical mapping of membrane potential.
AB  - BACKGROUND: It is believed that defibrillation is due to shock-induced changes of
      transmembrane potential (DeltaV(m)) in the bulk of ventricular myocardium (so
      called virtual electrodes), but experimental proof of this hypothesis is absent.
      Here, intramural shock-induced DeltaV(m) were measured for the first time in
      isolated preparations of left ventricle (LV) by an optical mapping technique.
      METHODS AND RESULTS: LV preparations were excised from porcine hearts (n=9) and
      perfused through a coronary artery. Rectangular shocks (duration 10 ms, field
      strength E approximately 2 to 50 V/cm) were applied across the wall during the
      action potential plateau by 2 large electrodes. Shock-induced DeltaV(m) were
      measured on the transmural wall surface with a 16x16 photodiode array (resolution
      1.2 mm/diode). Whereas weak shocks (E approximately 2 V/cm) induced negligible
      DeltaV(m) in the wall middle, stronger shocks produced intramural DeltaV(m) of 2
      types. (1) Shocks with E>4 V/cm produced both positive and negative intramural
      DeltaV(m) that changed their sign on changing shock polarity, possibly reflecting
      large-scale nonuniformities in the tissue structure; the DeltaV(m) patterns were
      asymmetrical, with DeltaV-(m)>DeltaV+(m). (2) Shocks with E>34 V/cm produced
      predominantly negative DeltaV(m) across the whole transmural surface, independent
      of the shock polarity. These relatively uniform polarizations could be a result
      of microscopic discontinuities in tissue structure. CONCLUSIONS: Strong
      defibrillation shocks induce DeltaV(m) in the intramural layers of LV. During
      action potential plateau, intramural DeltaV(m) are typically asymmetrical (DeltaV
      (m)>DeltaV+(m)) and become globally negative during very strong shocks.

PMID- 12186809
TI  - Principles from clinical trials relevant to clinical practice: Part I.

PMID- 12186810
TI  - Images in cardiovascular medicine. Pericardial adhesion shown in
      echocardiographic subxiphoid view in a patient with postsurgical pericardial
      constriction.

PMID- 12186811
TI  - ACC/AHA/NHLBI Clinical Advisory on the Use and Safety of Statins.

PMID- 12186813
TI  - AJRCCM's policy on duplicate publication: infrequently asked questions.

PMID- 12186814
TI  - Apoptosis as a potential mechanism of muscle cachexia in chronic obstructive
      pulmonary disease.

PMID- 12186815
TI  - Diagnostic tests for occupational asthma.

PMID- 12186816
TI  - Ups and downs of nitric oxide in chesty children.

PMID- 12186817
TI  - Bronchiolitis obliterans after human lung transplantation.

PMID- 12186818
TI  - Diisocyanate antigen-stimulated monocyte chemoattractant protein-1 synthesis has
      greater test efficiency than specific antibodies for identification of
      diisocyanate asthma.
AB  - We previously reported that diisocyanate-human serum albumin (DIISO-HSA)
      stimulated production of monocyte chemoattractant protein-1 (MCP-1) by peripheral
      blood mononuclear cells is significantly associated with a clinical diagnosis of
      diisocyanate asthma (DA). Others have reported that antibodies for DIISO-HSA are
      specific but insensitive markers of DA. This study was performed to evaluate test
      characteristics of the in vitro MCP-1 assay compared with DIISO-HSA-specific
      immunoglobulin (Ig) G and IgE in identifying workers with DA. MCP-1 was
      quantitated in peripheral blood mononuclear cell supernatants 48 hours after
      incubation with DIISO-HSA antigens. Assay results were compared with outcomes of
      specific inhalation challenge (SIC) testing. Nineteen of 54 (35%) workers assayed
      for antibodies and MCP-1 stimulation had SIC-confirmed DA. Mean MCP-1 produced by
      SIC-positive workers was greater than SIC-negative workers (p < or = 0.001).
      Diagnostic sensitivity, specificity, and test efficiency for specific IgG were
      47%, 74%, and 65%, respectively, and for specific IgE were 21%, 89%, and 65%,
      respectively. Sensitivity, specificity, and test efficiency of the MCP-1 test
      were 79%, 91%, and 87%, respectively. This study indicates that the MCP-1
      stimulation assay has greater sensitivity and specificity than the specific
      antibody assays in correctly identifying DA.

PMID- 12186819
TI  - Effect of interferon-gamma on allergic airway responses in interferon-gamma
      deficient mice.
AB  - Interferon (IFN)-gamma reduces airway responses after allergen challenge in mice.
      The mechanisms of this effect are not clear. These studies investigate whether
      IFN-gamma can reverse prolonged airway responses after allergen challenge in IFN
      gamma-deficient (IFN-gammaKO) mice. Sensitized mice (IFN-gammaKO and wild-type
      [WT]) were challenged with ovalbumin. Airway responsiveness, eosinophils in
      bronchoalveolar lavage fluid, and lung lymphocyte subsets (CD4(+) and CD8(+))
      were measured 24 hours and 8 weeks after challenge. In further experiments, we
      treated IFN-gammaKO mice with recombinant IFN-gamma starting 4 weeks after the
      challenge for 1 week or 4 weeks. Airway responsiveness, bronchoalveolar lavage
      eosinophils, and lung CD4(+) cells were increased 8 weeks after challenge in IFN
      gammaKO but not WT mice. IFN-gamma treatment returned lung CD4(+) cell numbers to
      values obtained in unchallenged mice. One week of IFN-gamma treatment also
      returned airway responsiveness to baseline levels; however, 4-week treatment with
      IFN-gamma failed to decrease airway responsiveness below levels observed in
      untreated animals. This suggests that IFN-gamma plays an essential role in
      reversing allergen-induced airway inflammation and hyperresponsiveness and that
      it may have dual actions on the latter. Observations that IFN-gamma reverses
      airway responses, even when administered after challenge, suggests that IFN-gamma
      treatment could control allergic disease, including asthma.

PMID- 12186820
TI  - Effects of glutathione S-transferase M1, maternal smoking during pregnancy, and
      environmental tobacco smoke on asthma and wheezing in children.
AB  - The rise in childhood asthma prevalence suggests a role for environmental factors
      in the etiology of this evolving epidemic; however, genetics also influence the
      occurrence of asthma. Glutathione S-transferase (GST) M1 may play a role in
      asthma and wheezing occurrence among those exposed to tobacco smoke, as it
      functions in pathways involved in asthma pathogenesis such as xenobiotic
      metabolism and antioxidant defenses. Effects of GSTM1 genotype, maternal smoking
      during pregnancy, and childhood environmental tobacco smoke (ETS) exposure on
      asthma and wheezing were investigated in 2,950 children enrolled in 4th, 7th, and
      10th grade classrooms in 12 Southern California communities. The effects of in
      utero exposure to maternal smoking on asthma and wheezing occurrence were largely
      restricted to children with GSTM1 null genotype. Among GSTM1 null children, in
      utero exposure was associated with increased prevalence of early onset asthma
      (odds ratio [OR] 1.6, 95% confidence interval [CI] 1.0-2.5), asthma with current
      symptoms (OR 1.7, 95% CI 1.1-2.8), persistent asthma (OR 1.6, 95% CI 1.1-2.4),
      lifetime history of wheezing (OR 1.8, 95% CI 1.3-2.5), wheezing with exercise (OR
      2.1, 95% CI 1.3-3.3), wheezing requiring medication (OR 2.2, 95% CI 1.4-3.4), and
      emergency room visits in the past year (OR 3.7, 95% CI 1.9-7.3). Among children
      with GSTM1 (+) genotype, in utero exposure was not associated with asthma or
      wheezing. Our findings indicate that there are important long-term effects of in
      utero exposure in a genetically susceptible group of children.

PMID- 12186821
TI  - Use of nasal cannula for detecting sleep apneas and hypopneas in infants and
      children.
AB  - We evaluated tolerance of nasal cannula (NC) by 14 infants (median age, 2.6
      months) and 16 children (median age, 5.5 years) with suspected obstructive sleep
      apnea syndrome and compared the efficacy of the NC with that of a nasobuccal
      thermistor in detecting obstructive apneas (OA) and obstructive hypopneas (OH) on
      polysomnography traces. The relationship between cannula flow and esophageal
      pressure was assessed in six patients. Time spent with an uninterpretable flow
      signal was longer when using a cannula than when using a thermistor in infants (p
      < 0.05) and children (p < 0.01), and it was longer in the younger patients (p <
      0.05). Among the 650 OA-OH detected by either method, only 38% were detected by
      both, and 58% were detected by the cannula and missed by the thermistor, so that
      the apnea-hypopnea index was higher with cannula than with thermistor in each age
      group (p < 0.01). More hypopneas than apneas were detected by the cannula and
      missed by the thermistor (p < 0.001). Out-of-phase thoracic and abdominal motions
      and/or changes in the end-tidal CO(2) signal shape were associated with 86% of OH
      identified by cannula. In the six patients whose esophageal pressure was
      measured, all respiratory events identified using a cannula were associated with
      increased "airway resistance." Thus, the NC is more likely than the thermistor to
      detect OA and OH in infants and children, and this superiority is particularly
      marked for hypopneas.

PMID- 12186822
TI  - Response of automatic continuous positive airway pressure devices to different
      sleep breathing patterns: a bench study.
AB  - Evaluating the usefulness of automatic continuous positive airway pressure (CPAP)
      in treating the sleep apnea-hypopnea syndrome (SAHS) is not easy because the
      algorithms for automatic CPAP implemented in the devices available are not well
      known and are probably dependent on the device. In addition, at present it is not
      possible to test the behavior of automatic CPAP devices in response to well
      defined breathing patterns. Our aim was to implement a bench test to characterize
      the responses of automatic CPAP devices by subjecting them to breathing patterns
      of patients with SAHS. To this end, a variety of typical breathing patterns
      (normal, apneas, hypopneas, flow limitation, snoring) previously recorded in
      patients with SAHS during sleep were reproduced by a breathing waveform
      generator. Five commercially available automatic CPAP devices were tested. The
      responses of the devices to apneas, hypopneas, flow limitation, and snoring were
      considerably different. In some devices, the response was modified by air leaks
      similar to the ones found in patients. Consequently, the effectiveness of
      automatic CPAP assessed in clinical tests performed by using particular devices
      has no general validity. Testing automatic CPAP devices in a bench study is a
      useful first step in evaluating the performance of this new type of device in
      adjusting nasal pressure for each patient.

PMID- 12186823
TI  - Analysis of error profiles occurring during the OSLER test: a sensitive mean of
      detecting fluctuations in vigilance in patients with obstructive sleep apnea
      syndrome.
AB  - The OSLER test represents a simple alternative to the maintenance of wakefulness
      test. Standard analysis of OSLER test results yields a mean sleep latency (MSL).
      The aim of this study was to use both MSL and errors (nonresponses to
      stimulations) to characterize daytime sleepiness in apneic patients. OSLER test
      results at 9:00 A.M., 11:00 A.M. and 1:30 P.M. were compared in 27 obstructive
      sleep apnea syndrome patients (50.4 +/- 10.4 years; apnea-hypopnea index: 43.05
      +/- 25.08) and 20 control subjects (C). Not only did obstructive sleep apnea
      syndrome patients demonstrate earlier sleep onset than control subjects (MSL:
      1,788 seconds +/- 511 versus 2,335 seconds +/- 139, p < 0.001), but they also
      spent a greater percentage of time making errors than control subjects (5.4% +/-
      4.7 of total test time versus 0.4% +/- 0.4, p < 0.001) with specific error
      profiles (high prevalence of three to six consecutive errors). When error profile
      analysis was added to standard sleep latency assessment, up to 40% of patients
      with normal sleep latency were exhibiting abnormal fluctuation in vigilance. A
      single 9:00 A.M. OSLER session appeared as sensitive as three consecutive
      sessions in its use as a means of identifying patients with significant daytime
      sleepiness. On the other hand, the 1:30 P.M. OSLER test session was least
      specific to distinguish apneic subjects from normal subjects, suggesting that the
      OSLER test can identify the afternoon peak in physiologic somnolence.

PMID- 12186824
TI  - Respiratory and limb muscle weakness induced by tumor necrosis factor-alpha:
      involvement of muscle myofilaments.
AB  - The respiratory and limb skeletal muscles become weakened in sepsis, congestive
      heart failure, and other inflammatory diseases. A potential mediator of muscle
      weakness is tumor necrosis factor (TNF)-alpha, a cytokine that can stimulate
      muscle wasting and also can induce contractile dysfunction without overt
      catabolism. This study addressed the latter process. Murine diaphragm and limb
      muscle (flexor digitorum brevis [FDB]) preparations were used to determine the
      relative sensitivities of these muscles to TNF-alpha. Intact muscle fibers were
      isolated from FDB and microinjected with indo-1 to measure changes in
      sarcoplasmic calcium regulation. We found that TNF-alpha depressed tetanic force
      of the diaphragm and FDB to comparable degrees across a range of stimulus
      frequencies. In isolated muscle fibers, TNF-alpha decreased tetanic force without
      altering tetanic calcium transients or resting calcium levels. We conclude that
      (1) TNF-alpha compromises contractile function of diaphragm and limb muscle
      similarly, and (2) TNF-alpha decreases force by blunting the response of muscle
      myofilaments to calcium activation.

PMID- 12186825
TI  - Skeletal muscle apoptosis and weight loss in chronic obstructive pulmonary
      disease.
AB  - Patients with chronic obstructive pulmonary disease (COPD) often lose weight
      during the course of their disease. We hypothesized that this may be due to
      skeletal muscle apoptosis. To investigate this possibility, we obtained
      quadriceps femoris biopsies in 15 patients with COPD (8 with normal body mass
      index [BMI] and 7 with low [< 20 kg/m(2)] BMI), 8 healthy volunteers, and 6
      sedentary subjects undergoing orthopedic surgery (both groups with normal BMI).
      Skeletal muscle apoptosis was assessed by the transferase-mediated dUTP nick end
      labeling (TUNEL) technique and the immunodetection of poly-(ADP-ribose)
      polymerase proteolytic fragments. Exercise tolerance on a cycloergometer was also
      determined in patients with COPD. We found that skeletal muscle apoptosis (by
      both techniques) was increased in patients with COPD and low BMI as compared with
      the other three groups (p < 0.005). In patients with COPD, BMI was inversely
      related to skeletal muscle apoptosis (TUNEL, p = 0.009), and it was better
      correlated with exercise capacity (p = 0.006) than with the degree of airflow
      obstruction present (p = 0.02). Markers of skeletal muscle apoptosis were not
      related to any of the measured lung function variables. This study shows that
      skeletal muscle apoptosis (1) is increased in patients with COPD having low BMI;
      and (2) is associated with a lower exercise tolerance despite a similar degree of
      lung function impairment.

PMID- 12186826
TI  - 4-Hydroxy-2-nonenal, a specific lipid peroxidation product, is elevated in lungs
      of patients with chronic obstructive pulmonary disease.
AB  - Cigarette smoking results in oxidative stress and inflammation in the lungs,
      which are involved in the pathogenesis of chronic obstructive pulmonary disease
      (COPD). 4-Hydroxy-2-nonenal (4-HNE), a highly reactive diffusible product of
      lipid peroxidation, is a key mediator of oxidant-induced cell signaling and
      apoptosis. 4-HNE has a high affinity toward cysteine, histidine, and lysine
      groups and forms direct protein adducts. We investigated the presence of 4-HNE
      modified proteins in lung tissue obtained from subjects with and without COPD. We
      studied 23 current or ex-smokers with similar smoking histories with COPD (n =
      11; FEV(1) < 70% predicted) or without COPD (n = 12; FEV(1) > 84% predicted) who
      had undergone lung resection. As 4-HNE and transforming growth factor-beta(1)
      (TGF-beta(1)) can modulate gamma-glutamylcysteine synthetase (gamma-GCS) mRNA
      levels in lung cells, we assessed the relations between 4-HNE-modified protein
      levels, FEV(1), gamma-GCS, and TGF-beta(1). 4-HNE-modified protein levels were
      elevated in airway and alveolar epithelial cells, endothelial cells, and
      neutrophils in subjects with COPD, compared with the levels in subjects without
      COPD (p < 0.01). We also observed a significant inverse correlation between the
      levels of 4-HNE adducts in alveolar epithelium, airway endothelium, and
      neutrophils and FEV(1) (p < 0.05) and a positive correlation between 4-HNE
      adducts and TGF-beta(1) protein and mRNA as well as gamma-GCS mRNA levels in
      airway and alveolar epithelium (p < 0.01). The elevated levels of 4-HNE may play
      a role in the signaling events in lung inflammation leading to the imbalance of
      the expression of both proinflammatory mediators and protective antioxidant genes
      in COPD.

PMID- 12186827
TI  - A novel oral neutrophil elastase inhibitor (ONO-6818) inhibits human neutrophil
      elastase-induced emphysema in rats.
AB  - We investigated the effects of a novel oral neutrophil elastase inhibitor (ONO
      6818) on acute lung injury and pulmonary emphysema induced by human neutrophil
      elastase (HNE). Young male Wistar rats were divided into four treatment groups:
      (1) control group (saline); (2) HNE group (HNE 200 U + 0.5% carboxymethyl
      cellulose [solution for ONO-6818]); (3) low-dose ONO-6818 group (HNE 200 U + ONO
      6818 10 mg/kg); and (4) high-dose ONO-6818 group (HNE 200 U + ONO-6818 100
      mg/kg). Saline and HNE were applied via the trachea using a microsprayer. ONO
      6818 was administered orally 1 hour before HNE application. Six hours after HNE
      application, neutrophil counts and hemoglobin concentration in bronchoalveolar
      lavage fluid and lung tissue myeloperoxidase activity were determined. Eight
      weeks after the application, FRC, TLC, lung compliance, and mean linear intercept
      were estimated. ONO-6818 attenuated dose-dependently HNE-induced increases in
      lung myeloperoxidase activity, hemoglobin, and neutrophil count in
      bronchoalveolar lavage fluid. Furthermore, it significantly attenuated HNE
      induced increases in FRC, TLC, lung compliance, and mean linear intercept. ONO
      6818 inhibited acute lung injury induced by HNE by minimizing lung hemorrhage and
      accumulation of neutrophils in the lung. ONO-6818 also inhibited the development
      of HNE-induced emphysematous changes including lung hyperinflation, degradation
      of elastic recoil, and airspace enlargement.

PMID- 12186828
TI  - Upper airway epithelial structural changes in obstructive sleep-disordered
      breathing.
AB  - The etiology of upper airway collapsibility in patients with snoring and
      obstructive sleep apnea (OSA) remains unclear. Structural mucosal changes could
      be contributory factors. The objective of this study was to determine whether
      pathologic changes in the epithelium or the epithelial-connective tissue
      interface are present in patients with snoring and/or OSA by means of scanning
      electron microscopy and immunohistochemistry. Uvulae were obtained by
      uvulopalatopharyngoplasty from three patients with habitual snoring and nine
      patients with mild to severe OSA, as well as by dissection from 43 nonsnoring
      body donors. Scanning electron microscopy revealed structural changes in the
      epithelial-connective tissue boundary that significantly differed from age
      related changes in the control subjects. The immunohistochemical staining with
      antibodies against epithelial cytokeratins showed differences in the expression
      pattern of cytokeratin 13 between patients and control subjects. No differences
      were found in the distribution pattern of laminin. Analysis of defense cells
      revealed a significant diffuse infiltration of leukocytes, mainly T cells, inside
      the lamina propria of the patient group, which was not observed in the control
      group. In conclusion, these results support the hypothesis that progressive
      structural changes in the mucosa caused by the trauma of snoring are a possible
      contributory factor to upper airway collapsibility.

PMID- 12186829
TI  - A rearranged form of Epstein-Barr virus DNA is associated with idiopathic
      pulmonary fibrosis.
AB  - An association between idiopathic pulmonary fibrosis (IPF) and productive Epstein
      Barr virus (EBV) infection has been found previously. Productive EBV replication
      can be associated with a rearrangement in EBV genomes termed WZhet. We
      hypothesized that WZhet genomes might be present in patients with IPF. Thirty
      nine patients with IPF, 26 lung transplant recipients, and 24 normal subjects
      were studied. When EBV DNA-positive lung tissue biopsies from IPF patients were
      analyzed, 11 of 18 (61%) were positive for WZhet. Buffy coat DNA analysis showed
      that 75-85% were EBV DNA-positive in both IPF and control groups. Buffy coat
      analysis for WZhet was positive in 16 of 27 (59%) IPF patients, compared with
      none of 32 lung transplant recipients and 1 of 24 (4%) normal blood donors (p <
      or = 0.001). There was thus a good correlation between the presence of WZhet in
      lung tissue and peripheral blood. However, there was no significant association
      between the presence of WZhet and immunosuppressive therapy. These data further
      confirm the association between active EBV infection and IPF and provide a
      potential marker in the peripheral blood for the tracking of EBV in this disease.

PMID- 12186830
TI  - Prevention of gram-negative translocation reduces the severity of hepatopulmonary
      syndrome.
AB  - Hepatopulmonary syndrome (HPS) is characterized by intrapulmonary vascular
      dilatations and an increased alveoloarterial oxygen difference (AaPO(2)). These
      abnormalities are related to augmented pulmonary nitric oxide (NO) production,
      dependent primarily on increases in the expression and activity of inducible NO
      synthase (iNOS) within pulmonary intravascular macrophages and, to a lesser
      extent, of endothelial NOS (eNOS). Production of iNOS by pulmonary intravascular
      macrophages might be related to translocated gut bacteria present in the
      pulmonary circulation. To test this hypothesis, we determined whether macrophage
      sequestration, lung iNOS expression and activity, and HPS severity were decreased
      after norfloxacin was given for 5 weeks to prevent Gram-negative bacterial
      translocation in rats with common bile duct ligation-induced cirrhosis.
      Norfloxacin decreased the incidence of Gram-negative translocation from 70 to 0%
      and the percentage of pulmonary microvessels containing more than 10 macrophages
      from 52 +/- 7 to 21 +/- 8% (p < 0.01). AaPO(2) and cerebral uptake of intravenous
      (99m)Tc-labeled albumin macroaggregates (reflecting intrapulmonary vascular
      dilatations) were intermediate to those of untreated cirrhotic and sham-operated
      rats. The activity and expression of lung iNOS, but not eNOS, were reduced to
      normal. Norfloxacin may reduce HPS severity by inhibiting Gram-negative bacterial
      translocation, thereby decreasing NO production by pulmonary intravascular
      macrophages. Bacterial translocation may be the key to the pathogenesis of HPS.

PMID- 12186831
TI  - ATS/ERS Statement on respiratory muscle testing.

PMID- 12186832
TI  - Duplicate publication.

PMID- 12186833
TI  - Notice of duplicate publication.

PMID- 12186834
TI  - Is maturation required for Langerhans cell migration?

PMID- 12186835
TI  - Accumulation of immature Langerhans cells in human lymph nodes draining
      chronically inflamed skin.
AB  - The coordinated migration and maturation of dendritic cells (DCs) such as
      intraepithelial Langerhans cells (LCs) is considered critical for T cell priming
      in response to inflammation in the periphery. However, little is known about the
      role of inflammatory mediators for LC maturation and recruitment to lymph nodes
      in vivo. Here we show in human dermatopathic lymphadenitis (DL), which features
      an expanded population of LCs in one draining lymph node associated with
      inflammatory lesions in its tributary skin area, that the Langerin/CD207(+) LCs
      constitute a predominant population of immature DCs, which express CD1a, and
      CD68, but not CD83, CD86, and DC-lysosomal-associated membrane protein
      (LAMP)/CD208. Using LC-type cells generated in vitro in the presence of
      transforming growth factor (TGF)-beta1, we further found that tumor necrosis
      factor (TNF)-alpha, as a prototype proinflammatory factor, and a variety of
      inflammatory stimuli and bacterial products, increase Langerin expression and
      Langerin dependent Birbeck granules formation in cell which nevertheless lack
      costimulatory molecules, DC-LAMP/CD208 and potent T cell stimulatory activity but
      express CCR7 and respond to the lymph node homing chemokines CCL19 and CCL21.
      This indicates that LC migration and maturation can be independently regulated
      events. We suggest that during DL, inflammatory stimuli in the skin increase the
      migration of LCs to the lymph node but without associated maturation. Immature
      LCs might regulate immune responses during chronic inflammation.

PMID- 12186836
TI  - Blockade of HIV-1 infection of New World monkey cells occurs primarily at the
      stage of virus entry.
AB  - HIV-1 naturally infects chimpanzees and humans, but does not infect Old World
      monkeys because of replication blocks that occur after virus entry into the cell.
      To understand the species-specific restrictions operating on HIV-1 infection, the
      ability of HIV-1 to infect the cells of New World monkeys was examined. Primary
      cells derived from common marmosets and squirrel monkeys support every phase of
      HIV-1 replication with the exception of virus entry. Efficient HIV-1 entry
      typically requires binding of the viral envelope glycoproteins and host cell
      receptors, CD4 and either CCR5 or CXCR4 chemokine receptors. HIV-1 did not
      detectably bind or utilize squirrel monkey CD4 for entry, and marmoset CD4 was
      also very inefficient compared with human CD4. A marmoset CD4 variant, in which
      residues 48 and 59 were altered to the amino acids found in human CD4, supported
      HIV-1 entry efficiently. The CXCR4 molecules of both marmosets and squirrel
      monkeys supported HIV-1 infection, but the CCR5 proteins of both species were
      only marginally functional. These results demonstrate that the CD4 and CCR5
      proteins of New World monkeys represent the major restriction against HIV-1
      replication in these primates. Directed adaptation of the HIV-1 envelope
      glycoproteins to common marmoset receptors might allow the development of New
      World monkey models of HIV-1 infection.

PMID- 12186837
TI  - Inhibition of allogeneic T cell proliferation by indoleamine 2,3-dioxygenase
      expressing dendritic cells: mediation of suppression by tryptophan metabolites.
AB  - Indoleamine 2,3-dioxygenase (IDO), an enzyme involved in the catabolism of
      tryptophan, is expressed in certain cells and tissues, particularly in antigen
      presenting cells of lymphoid organs and in the placenta. It was shown that IDO
      prevents rejection of the fetus during pregnancy, probably by inhibiting
      alloreactive T cells, and it was suggested that IDO-expression in antigen
      presenting cells may control autoreactive immune responses. Degradation of
      tryptophan, an essential amino acid required for cell proliferation, was reported
      to be the mechanism of IDO-induced T cell suppression. Because we wanted to study
      the action of IDO-expressing dendritic cells (DCs) on allogeneic T cells, the
      human IDO gene was inserted into an adenoviral vector and expressed in DCs.
      Transgenic DCs decreased the concentration of tryptophan, increased the
      concentration of kynurenine, the main tryptophan metabolite, and suppressed
      allogeneic T cell proliferation in vitro. Kynurenine, 3-hydroxykynurenine, and 3
      hydroxyanthranilic acid, but no other IDO-induced tryptophan metabolites,
      suppressed the T cell response, the suppressive effects being additive. T cells,
      once stopped in their proliferation, could not be restimulated. Inhibition of
      proliferation was likely due to T cell death because suppressive tryptophan
      catabolites exerted a cytotoxic action on CD3(+) cells. This action
      preferentially affected activated T cells and increased gradually with exposure
      time. In addition to T cells, B and natural killer (NK) cells were also killed,
      whereas DCs were not affected. Our findings shed light on suppressive mechanisms
      mediated by DCs and provide an explanation for important biological processes in
      which IDO activity apparently is increased, such as protection of the fetus from
      rejection during pregnancy and possibly T cell death in HIV-infected patients.

PMID- 12186838
TI  - Tryptophan-derived catabolites are responsible for inhibition of T and natural
      killer cell proliferation induced by indoleamine 2,3-dioxygenase.
AB  - Macrophages exposed to macrophage colony-stimulating factor acquire the capacity
      to suppress T cell proliferation; this effect is associated with de novo
      expression of the tryptophan-catabolizing enzyme indoleamine 2,3-dioxygenase
      (IDO). We have purified IDO and tested its activity in in vitro models of T cell
      activation. IDO was able to inhibit proliferation of CD4(+) T lymphocytes, CD8(+)
      T lymphocytes, and natural killer (NK) cells; proliferation of B lymphocytes was
      not affected. The inhibitory role of tryptophan and of its catabolites was then
      tested. In the presence of tryptophan, only L-kynurenine and picolinic acid
      inhibit cell proliferation. In a tryptophan-free medium cell proliferation was
      not affected. In the absence of tryptophan inhibition induced by L-kynurenine and
      picolinic acid was observed at concentrations below the lowest concentration that
      was effective in the presence of tryptophan, and quinolinic acid acquired some
      inhibitory capacity. Inhibition of cell proliferation induced by the tryptophan
      catabolites resulting from IDO activity was selective, applying only to cells
      undergoing activation. Resting cells were not affected and could subsequently
      activate normally. We suggest that IDO exerts its effect on cell proliferation by
      (i) starting the cascade of biochemical reactions that produce the three
      catabolites and by (ii) enhancing their inhibitory potential by depriving the
      extracellular microenvironment of tryptophan.

PMID- 12186839
TI  - Evidence for replicative repair of DNA double-strand breaks leading to oncogenic
      translocation and gene amplification.
AB  - Nonreciprocal translocations and gene amplifications are commonly found in human
      tumors. Although little is known about the mechanisms leading to such
      aberrations, tissue culture models predict that they can arise from DNA breakage,
      followed by cycles of chromatid fusion, asymmetric mitotic breakage, and
      replication. Mice deficient in both a nonhomologous end joining (NHEJ) DNA repair
      protein and the p53 tumor suppressor develop lymphomas at an early age harboring
      amplification of an IgH/c-myc fusion. Here we report that these chromosomal
      rearrangements are initiated by a recombination activating gene (RAG)-induced DNA
      cleavage. Subsequent DNA repair events juxtaposing IgH and c-myc are mediated by
      a break-induced replication pathway. Cycles of breakage-fusion-bridge result in
      amplification of IgH/c-myc while chromosome stabilization occurs through telomere
      capture. Thus, mice deficient in NHEJ provide excellent models to study the
      etiology of unbalanced translocations and amplification events during
      tumorigenesis.

PMID- 12186840
TI  - CD4(+) T cells from glutamic acid decarboxylase (GAD)65-specific T cell receptor
      transgenic mice are not diabetogenic and can delay diabetes transfer.
AB  - Glutamic acid decarboxylase (GAD)65 is an early and important antigen in both
      human diabetes mellitus and the nonobese diabetic (NOD) mouse. However, the exact
      role of GAD65-specific T cells in diabetes pathogenesis is unclear. T cell
      responses to GAD65 occur early in diabetes pathogenesis, yet only one GAD65
      specific T cell clone of many identified can transfer diabetes. We have generated
      transgenic mice on the NOD background expressing a T cell receptor (TCR)-specific
      for peptide epitope 286-300 (p286) of GAD65. These mice have GAD65-specific
      CD4(+) T cells, as shown by staining with an I-A(g7)(p286) tetramer reagent.
      Lymphocytes from these TCR transgenic mice proliferate and make interferon gamma,
      interleukin (IL)-2, tumor necrosis factor (TNF)-alpha, and IL-10 when stimulated
      in vitro with GAD65 peptide 286-300, yet these TCR transgenic animals do not
      spontaneously develop diabetes, and insulitis is virtually undetectable.
      Furthermore, in vitro activated CD4 T cells from GAD 286 TCR transgenic mice
      express higher levels of CTL-associated antigen (CTLA)-4 than nontransgenic
      littermates. CD4(+) T cells, or p286-tetramer(+)CD4(+) Tcells, from GAD65 286-300
      specific TCR transgenic mice delay diabetes induced in NOD.scid mice by diabetic
      NOD spleen cells. This data suggests that GAD65 peptide 286-300-specific T cells
      have disease protective capacity and are not pathogenic.

PMID- 12186841
TI  - Surface cathepsin B protects cytotoxic lymphocytes from self-destruction after
      degranulation.
AB  - The granule exocytosis cytotoxicity pathway is the major molecular mechanism for
      cytotoxic T lymphocyte (CTL) and natural killer (NK) cytotoxicity, but the
      question of how these cytotoxic lymphocytes avoid self-destruction after
      secreting perforin has remained unresolved. We show that CTL and NK cells die
      within a few hours if they are triggered to degranulate in the presence of
      nontoxic thiol cathepsin protease inhibitors. The potent activity of the
      impermeant, highly cathepsin B-specific membrane inhibitors CA074 and NS-196
      strongly implicates extracellular cathepsin B. CTL suicide in the presence of
      cathepsin inhibitors requires the granule exocytosis cytotoxicity pathway, as it
      is normal with CTLs from gld mice, but does not occur in CTLs from perforin
      knockout mice. Flow cytometry shows that CTLs express low to undetectable levels
      of cathepsin B on their surface before degranulation, with a substantial rapid
      increase after T cell receptor triggering. Surface cathepsin B eluted from live
      CTL after degranulation by calcium chelation is the single chain processed form
      of active cathepsin B. Degranulated CTLs are surface biotinylated by the
      cathepsin B-specific affinity reagent NS-196, which exclusively labels
      immunoreactive cathepsin B. These experiments support a model in which granule
      derived surface cathepsin B provides self-protection for degranulating cytotoxic
      lymphocytes.

PMID- 12186842
TI  - Bacteria-triggered CD4(+) T regulatory cells suppress Helicobacter hepaticus
      induced colitis.
AB  - We have previously demonstrated that interleukin (IL)-10-deficient (IL-10
      knockout [KO]) but not wild-type (WT) mice develop colitis after infection with
      Helicobacter hepaticus. Here, we show that infected recombination activating gene
      (RAG) KO mice develop intestinal inflammation after reconstitution with CD4(+) T
      cells from IL-10 KO animals and that the cotransfer of CD4(+) T cells from H.
      hepaticus-infected but not uninfected WT mice prevents this colitis. The disease
      protective WT CD4(+) cells are contained within the CD45RB(low) fraction and
      unexpectedly were found in both the CD25(+) and the CD25(-) subpopulations of
      these cells, their frequency being higher in the latter. The mechanism by which
      CD25(+) and CD25(-) CD45RB(low) CD4(+) cells block colitis involves IL-10 and not
      transforming growth factor (TGF)-beta, as treatment with anti-IL-10R but not anti
      TGF-beta monoclonal antibody abrogated their protective effect. In vitro,
      CD45RB(low) CD4(+) cells from infected WT mice were shown to produce IL-10 and
      suppress interferon-gamma production by IL-10 KO CD4(+) cells in an H. hepaticus
      antigen-specific manner. Together, our data support the concept that H. hepaticus
      infection results in the induction in WT mice of regulatory T cells that prevent
      bacteria-induced colitis. The induction of such cells in response to gut flora
      may be a mechanism protecting normal individuals against inflammatory bowel
      disease.

PMID- 12186843
TI  - The CD16(+) (FcgammaRIII(+)) subset of human monocytes preferentially becomes
      migratory dendritic cells in a model tissue setting.
AB  - Much remains to be learned about the physiologic events that promote monocytes to
      become lymph-homing dendritic cells (DCs). In a model of transendothelial
      trafficking, some monocytes become DCs in response to endogenous signals. These
      DCs migrate across endothelium in the ablumenal-to-lumenal direction (reverse
      transmigration), reminiscent of the migration into lymphatic vessels. Here we
      show that the subpopulation of monocytes that expresses CD16 (Fcgamma receptor
      III) is predisposed to become migratory DCs. The vast majority of cells derived
      from CD16(+) monocytes reverse transmigrated, and their presence was associated
      with migratory cells expressing high levels of CD86 and human histocompatibility
      leukocyte antigen (HLA)-DR, and robust capacity to induce allogeneic T cell
      proliferation. A minority of CD16(-) monocytes reverse transmigrated, and these
      cells stimulated T cell proliferation less efficiently. CD16 was not functionally
      required for reverse transmigration, but promoted cell survival when yeast
      particles (zymosan) were present as a maturation stimulus in the subendothelial
      matrix. The cell surface phenotype and migratory characteristics of CD16(+)
      monocytes were inducible in CD16(-) monocytes by preincubation with TGFbeta1. We
      propose that CD16(+) monocytes may contribute significantly to precursors for DCs
      that transiently survey tissues and migrate to lymph nodes via afferent lymphatic
      vessels.

PMID- 12186846
TI  - Targeting mucosal sites by polymeric immunoglobulin receptor-directed peptides.
AB  - Polymeric immunoglobulins provide first line humoral defense at mucosal surfaces
      to which they are specifically transported by the polymeric immunoglobulin
      receptor (pIgR) on mucosal and glandular epithelial cells. Previous studies from
      our laboratory suggested that amino acids 402-410 of the Calpha3 domain of
      dimeric IgA (dIgA) represented a potential binding site for the pIgR. Here by
      binding human secretory component to overlapping decapeptides of Calpha3, we
      confirm these residues and also uncover an additional site. Furthermore, we show
      that the Calpha3 motif appears to be sufficient to direct transport of green
      fluorescent protein through the pIgR-specific cellular transcytosis system. An
      alternative approach identified phage peptides, selected from a library by the in
      vitro Madin Darby Canine Kidney transcytosis assay, for pIgR-mediated transport
      through epithelial cells. Some transcytosis-selected peptides map to the same 402
      410 pIgR-binding Calpha3 site. Further in vivo studies document that at least one
      of these peptides is transported in a rat model measuring hepatic bile transport.
      In addition to identifying small peptides that are both bound and transported by
      the pIgR, this study provides evidence that the pIgR-mediated mucosal secretion
      system may represent a means of targeting small molecule therapeutics and genes
      to mucosal epithelial cells.

PMID- 12186845
TI  - Reversal of tumor-induced dendritic cell paralysis by CpG immunostimulatory
      oligonucleotide and anti-interleukin 10 receptor antibody.
AB  - Progressing tumors in man and mouse are often infiltrated by dendritic cells
      (DCs). Deficient antitumor immunity could be related to a lack of tumor
      associated antigen (TAA) presentation by tumor-infiltrating DCs (TIDCs) or to a
      functional defect of TIDCs. Here we investigated the phenotype and function of
      TIDCs in transplantable and transgenic mouse tumor models. Although TIDCs could
      encompass various known DC subsets, most had an immature phenotype. We observed
      that TIDCs were able to present TAA in the context of major histocompatibility
      complex class I but that they were refractory to stimulation with the combination
      of lipopolysaccharide, interferon gamma, and anti-CD40 antibody. We could revert
      TIDC paralysis, however, by in vitro or in vivo stimulation with the combination
      of a CpG immunostimulatory sequence and an anti-interleukin 10 receptor (IL-10R)
      antibody. CpG or anti-IL-10R alone were inactive in TIDCs, whereas CpG triggered
      activation in normal DCs. In particular, CpG plus anti-IL-10R enhanced the TAA
      specific immune response and triggered de novo IL-12 production. Subsequently,
      CpG plus anti-IL-10R treatment showed robust antitumor therapeutic activity
      exceeding by far that of CpG alone, and elicited antitumor immune memory.

PMID- 12186844
TI  - Analysis of protease activity in live antigen-presenting cells shows regulation
      of the phagosomal proteolytic contents during dendritic cell activation.
AB  - Here, we describe a new approach designed to monitor the proteolytic activity of
      maturing phagosomes in live antigen-presenting cells. We find that an ingested
      particle sequentially encounters distinct protease activities during phagosomal
      maturation. Incorporation of active proteases into the phagosome of the
      macrophage cell line J774 indicates that phagosome maturation involves
      progressive fusion with early and late endocytic compartments. In contrast,
      phagosome biogenesis in bone marrow-derived dendritic cells (DCs) and macrophages
      preferentially involves endocytic compartments enriched in cathepsin S. Kinetics
      of phagosomal maturation is faster in macrophages than in DCs. Furthermore, the
      delivery of active proteases to the phagosome is significantly reduced after the
      activation of DCs with lipopolysaccharide. This observation is in agreement with
      the notion that DCs prevent the premature destruction of antigenic determinants
      to optimize T cell activation. Phagosomal maturation is therefore a tightly
      regulated process that varies according to the type and differentiation stage of
      the phagocyte.

PMID- 12186847
TI  - The youth revolution: cell biology in Japan.

PMID- 12186848
TI  - Sweet solution: sugars to the rescue.
AB  - Sugar pills are usually placebos, but Smith et al. (2002, this issue) use one to
      rescue designer mice unable to make GDP-Fucose. Dietary fucose enters a salvage
      pathway and spares the mice. Sound simple? Not so. Unknown genetic factors
      determine life or death.

PMID- 12186849
TI  - A survival pathway for Caenorhabditis elegans with a blocked unfolded protein
      response.
AB  - The unfolded protein response (UPR) counteracts stress caused by unprocessed ER
      client proteins. A genome-wide survey showed impaired induction of many UPR
      target genes in xbp-1 mutant Caenorhabditis elegans that are unable to signal in
      the highly conserved IRE1-dependent UPR pathway. However a family of genes, abu
      (activated in blocked UPR), was induced to higher levels in ER-stressed xbp-1
      mutant animals than in ER-stressed wild-type animals. RNA-mediated interference
      (RNAi) inactivation of a representative abu family member, abu-1 (AC3.3),
      activated the ER stress marker hsp-4::gfp in otherwise normal animals and killed
      50% of ER-stressed ire-1 and xbp-1 mutant animals. Abu-1(RNAi) also enhanced the
      effect of inactivation of sel-1, an ER-associated protein degradation gene. The
      nine abu genes encode highly related type I transmembrane proteins whose lumenal
      domains have sequence similarity to a mammalian cell surface scavenger receptor
      of endothelial cells that binds chemically modified extracellular proteins and
      directs their lysosomal degradation. Our findings that ABU-1 is an intracellular
      protein located within the endomembrane system that is induced by ER stress in
      xbp-1 mutant animals suggest that ABU proteins may interact with abnormal ER
      client proteins and this function may be particularly important in animals with
      an impaired UPR.

PMID- 12186850
TI  - The human silent information regulator (Sir)2 homologue hSIRT3 is a mitochondrial
      nicotinamide adenine dinucleotide-dependent deacetylase.
AB  - The yeast silent information regulator (Sir)2 protein links cellular metabolism
      and transcriptional silencing through its nicotinamide adenine dinucleotide (NAD)
      dependent histone deacetylase activity. We report that mitochondria from
      mammalian cells contain intrinsic NAD-dependent deacetylase activity. This
      activity is inhibited by the NAD hydrolysis product nicotinamide, but not by
      trichostatin A, consistent with a class III deacetylase. We identify this
      deacetylase as the nuclear-encoded human Sir2 homologue hSIRT3, and show that
      hSIRT3 is located within the mitochondrial matrix. Mitochondrial import of hSIRT3
      is dependent on an NH2-terminal amphipathic alpha-helix rich in basic residues.
      hSIRT3 is proteolytically processed in the mitochondrial matrix to a 28-kD
      product. This processing can be reconstituted in vitro with recombinant
      mitochondrial matrix processing peptidase (MPP) and is inhibited by mutation of
      arginines 99 and 100. The unprocessed form of hSIRT3 is enzymatically inactive
      and becomes fully activated in vitro after cleavage by MPP. These observations
      demonstrate the existence of a latent class III deacetylase that becomes
      catalytically activated upon import into the human mitochondria.

PMID- 12186851
TI  - Rab32 is an A-kinase anchoring protein and participates in mitochondrial
      dynamics.
AB  - A-kinase anchoring proteins (AKAPs) tether the cAMP-dependent protein kinase
      (PKA) and other signaling enzymes to distinct subcellular organelles. Using the
      yeast two-hybrid approach, we demonstrate that Rab32, a member of the Ras
      superfamily of small molecular weight G-proteins, interacts directly with the
      type II regulatory subunit of PKA. Cellular and biochemical studies confirm that
      Rab32 functions as an AKAP inside cells. Anchoring determinants for PKA have been
      mapped to sites within the conserved alpha5 helix that is common to all Rab
      family members. Subcellular fractionation and immunofluorescent approaches
      indicate that Rab32 and a proportion of the cellular PKA pool are associated with
      mitochondria. Transient transfection of a GTP binding-deficient mutant of Rab32
      promotes aberrant accumulation of mitochondria at the microtubule organizing
      center. Further analysis of this mutant indicates that disruption of the
      microtubule cytoskeleton results in aberrantly elongated mitochondria. This
      implicates Rab32 as a participant in synchronization of mitochondrial fission.
      Thus, Rab32 is a dual function protein that participates in both mitochondrial
      anchoring of PKA and mitochondrial dynamics.

PMID- 12186853
TI  - Plakoglobin is required for maintenance of the cortical actin skeleton in early
      Xenopus embryos and for cdc42-mediated wound healing.
AB  - Early Xenopus embryos are large, and during the egg to gastrula stages, when
      there is little extracellular matrix, the cytoskeletons of the individual
      blastomeres are thought to maintain their spherical architecture and provide
      scaffolding for the cellular movements of gastrulation. We showed previously that
      depletion of plakoglobin protein during the egg to gastrula stages caused
      collapse of embryonic architecture. Here, we show that this is due to loss of the
      cortical actin skeleton after depletion of plakoglobin, whereas the microtubule
      and cytokeratin skeletons are still present. As a functional assay for the actin
      skeleton, we show that wound healing, an actin-based behavior in embryos, is also
      abrogated by plakoglobin depletion. Both wound healing and the amount of cortical
      actin are enhanced by overexpression of plakoglobin. To begin to identify links
      between plakoglobin and the cortical actin polymerization machinery, we show here
      that the Rho family GTPase cdc42, is required for wound healing in the Xenopus
      blastula. Myc-tagged cdc42 colocalizes with actin in purse-strings surrounding
      wounds. Overexpression of cdc42 dramatically enhances wound healing, whereas
      depletion of maternal cdc42 mRNA blocks it. In combinatorial experiments we show
      that cdc42 cannot rescue the effects of plakoglobin depletion, showing that
      plakoglobin is required for cdc42-mediated cortical actin assembly during wound
      healing. However, plakoglobin does rescue the effect of cdc42 depletion,
      suggesting that cdc42 somehow mediates the distribution or function of
      plakoglobin. Depletion of alpha-catenin does not remove the cortical actin
      skeleton, showing that plakoglobin does not mediate its effect by its known
      linkage through alpha-catenin to the actin skeleton. We conclude that in Xenopus,
      the actin skeleton is a major determinant of cell shape and overall architecture
      in the early embryo, and that plakoglobin plays an essential role in the
      assembly, maintenance, or organization of this cortical actin.

PMID- 12186852
TI  - Gene replacement in mice reveals that the heavily phosphorylated tail of
      neurofilament heavy subunit does not affect axonal caliber or the transit of
      cargoes in slow axonal transport.
AB  - The COOH-terminal tail of mammalian neurofilament heavy subunit (NF-H), the
      largest neurofilament subunit, contains 44-51 lysine-serine-proline repeats that
      are nearly stoichiometrically phosphorylated after assembly into neurofilaments
      in axons. Phosphorylation of these repeats has been implicated in promotion of
      radial growth of axons, control of nearest neighbor distances between
      neurofilaments or from neurofilaments to other structural components in axons,
      and as a determinant of slow axonal transport. These roles have now been tested
      through analysis of mice in which the NF-H gene was replaced by one deleted in
      the NF-H tail. Loss of the NF-H tail and all of its phosphorylation sites does
      not affect the number of neurofilaments, alter the ratios of the three
      neurofilament subunits, or affect the number of microtubules in axons.
      Additionally, it does not reduce interfilament spacing of most neurofilaments,
      the speed of action potential propagation, or mature cross-sectional areas of
      large motor or sensory axons, although its absence slows the speed of acquisition
      of normal diameters. Most surprisingly, at least in optic nerve axons, loss of
      the NF-H tail does not affect the rate of transport of neurofilament subunits.

PMID- 12186854
TI  - Notch1 control of oligodendrocyte differentiation in the spinal cord.
AB  - We have selectively inhibited Notch1 signaling in oligodendrocyte precursors
      (OPCs) using the Cre/loxP system in transgenic mice to investigate the role of
      Notch1 in oligodendrocyte (OL) development and differentiation. Early development
      of OPCs appeared normal in the spinal cord. However, at embryonic day 17.5,
      premature OL differentiation was observed and ectopic immature OLs were present
      in the gray matter. At birth, OL apoptosis was strongly increased in Notch1
      mutant animals. Premature OL differentiation was also observed in the cerebrum,
      indicating that Notch1 is required for the correct spatial and temporal
      regulation of OL differentiation in various regions of the central nervous
      system. These findings establish a widespread function of Notch1 in the late
      steps of mammalian OPC development in vivo.

PMID- 12186855
TI  - REN: a novel, developmentally regulated gene that promotes neural cell
      differentiation.
AB  - Expansion and fate choice of pluripotent stem cells along the neuroectodermal
      lineage is regulated by a number of signals, including EGF, retinoic acid, and
      NGF, which also control the proliferation and differentiation of central nervous
      system (CNS) and peripheral nervous system (PNS) neural progenitor cells. We
      report here the identification of a novel gene, REN, upregulated by neurogenic
      signals (retinoic acid, EGF, and NGF) in pluripotent embryonal stem (ES) cells
      and neural progenitor cell lines in association with neurotypic differentiation.
      Consistent with a role in neural promotion, REN overexpression induced neuronal
      differentiation as well as growth arrest and p27Kip1 expression in CNS and PNS
      neural progenitor cell lines, and its inhibition impaired retinoic acid induction
      of neurogenin-1 and NeuroD expression. REN expression is developmentally
      regulated, initially detected in the neural fold epithelium of the mouse embryo
      during gastrulation, and subsequently throughout the ventral neural tube, the
      outer layer of the ventricular encephalic neuroepithelium and in neural crest
      derivatives including dorsal root ganglia. We propose that REN represents a novel
      component of the neurogenic signaling cascade induced by retinoic acid, EGF, and
      NGF, and is both a marker and a regulator of neuronal differentiation.

PMID- 12186858
TI  - The reprolysin jararhagin, a snake venom metalloproteinase, functions as a
      fibrillar collagen agonist involved in fibroblast cell adhesion and signaling.
AB  - The integrins alpha(2)beta(1) and alpha(1)beta(1) have been shown to modulate
      cellular activities of fibroblasts on contact with fibrillar collagen. Previously
      it has been shown that collagen binding to alpha(2)beta(1) regulates matrix
      metalloproteinase MMP-1 and membrane-type MT1-MMP expression. Jararhagin is a
      snake venom metalloproteinase of the Reprolysin family of zinc
      metalloproteinases, containing a metalloproteinase domain followed by disintegrin
      like and cysteine-rich domains. Jararhagin blocks type I collagen-induced
      platelet aggregation by binding to the alpha(2)beta(1) integrin and inhibiting
      collagen-mediated intracellular signaling events. Here we present evidence that,
      in contrast to the observations in platelets, jararhagin binding to the integrin
      receptor alpha(2)beta(1) in fibroblasts produces collagen-like cell signaling
      events such as up-regulation of MMP-1 and MT1-MMP. Inactivation of the
      metalloproteinase domain had no effect on these properties of jararhagin. Thus,
      in fibroblasts the snake venom metalloproteinase jararhagin functions as a
      collagen-mimetic substrate that binds to and activates integrins. Given the
      homology between the metalloproteinase, disintegrin-like and cysteine-rich
      domains of jararhagin and those of the members of the ADAMs (a disintegrin-like
      and metalloproteinase) family of proteins, this work demonstrates the potential
      of the disintegrin-like/cysteine-rich domains in the ADAMs as cellular signaling
      agents to elicit responses relevant to the biological function of these proteins.

PMID- 12186856
TI  - Novel PtdIns(3)P-binding protein Etf1 functions as an effector of the Vps34
      PtdIns 3-kinase in autophagy.
AB  - Autophagy is the process whereby cytoplasmic cargo (e.g., protein and organelles)
      are sequestered within a double membrane-enclosed transport vesicle and degraded
      after vesicle fusion with the vacuole/lysosome. Current evidence suggests that
      the Vps34 phosphatidylinositol 3-kinase is essential for macroautophagy, a
      starvation-induced autophagy pathway (Kihara et al., 2001). Here, we characterize
      a requirement for Vps34 in constitutive autophagy by the cytoplasm-to-vacuole
      targeting (Cvt) pathway. First, we show that transient disruption of
      phosphatidylinositol (PtdIns) 3-phosphate (PtdIns[3]P) synthesis through
      inactivation of temperature-sensitive Vps34 or its upstream activator, Vps15,
      blocks the Cvt and macroautophagy pathways. Yet, PtdIns(3)P-binding FYVE domain
      containing proteins, which mediate carboxypeptidase Y (CPY) transport to the
      vacuole by the CPY pathway, do not account for the requirement of Vps34 in
      autophagy. Using a genetic selection designed to isolate PtdIns(3)P-binding
      effectors of Vps34, we identify Etf1, an uncharacterized type II transmembrane
      protein. Although Etf1 does not contain a known 3-phosphoinositide-binding domain
      (i.e., FYVE or Phox), we find that Etf1 interacts with PtdIns(3)P and that this
      interaction requires a basic amino acid motif (KKPAKK) within the cytosolic
      region of the protein. Moreover, deletion of ETF1 or mutation of the KKPAKK motif
      results in strong sorting defects in the Cvt pathway but not in macroautophagy or
      in CPY sorting. We propose that Vps34 regulates the CPY, Cvt, and macroautophagy
      pathways through distinct sets of PtdIns(3)P-binding effectors and that Vps34
      promotes protein trafficking in the Cvt pathway through activation/localization
      of the effector protein Etf1.

PMID- 12186857
TI  - Conditional control of selectin ligand expression and global fucosylation events
      in mice with a targeted mutation at the FX locus.
AB  - Glycoprotein fucosylation enables fringe-dependent modulation of signal
      transduction by Notch transmembrane receptors, contributes to selectin-dependent
      leukocyte trafficking, and is faulty in leukocyte adhesion deficiency (LAD) type
      II, also known as congenital disorder of glycosylation (CDG)-IIc, a rare human
      disorder characterized by psychomotor defects, developmental abnormalities, and
      leukocyte adhesion defects. We report here that mice with an induced null
      mutation in the FX locus, which encodes an enzyme in the de novo pathway for GDP
      fucose synthesis, exhibit a virtually complete deficiency of cellular
      fucosylation, and variable frequency of intrauterine demise determined by
      parental FX genotype. Live-born FX(-/-) mice exhibit postnatal failure to thrive
      that is suppressed with a fucose-supplemented diet. FX(-/-) adults suffer from an
      extreme neutrophilia, myeloproliferation, and absence of leukocyte selectin
      ligand expression reminiscent of LAD-II/CDG-IIc. Contingent restoration of
      leukocyte and endothelial selectin ligand expression, general cellular
      fucosylation, and normal postnatal physiology is achieved by modulating dietary
      fucose to supply a salvage pathway for GDP-fucose synthesis. Conditional control
      of fucosylation in FX(-/-) mice identifies cellular fucosylation events as
      essential concomitants to fertility, early growth and development, and leukocyte
      adhesion.

PMID- 12186859
TI  - A new type 2 copper cysteinate azurin. Involvement of an engineered exposed
      cysteine in copper binding through internal rearrangement.
AB  - The double mutant H117G/N42C azurin exhibits tetragonal type 2 copper site
      characteristics with Cys(42) as one of the copper ligands as concluded from
      spectroscopic evidence (UV-visible, EPR, and resonance Raman). Analysis of the
      kinetics of copper uptake by the apoprotein by means of stopped flow spectroscopy
      suggests that the solvent-exposed Cys(42) assists in binding the metal ion and
      carrying it over to the active site where it becomes coordinated by, among
      others, a second cysteine, Cys(112). A structure is proposed in which the loop
      from residue 36 to 47 has rearranged to form a tetragonal type 2 copper site with
      Cys(42) as one of the ligands. The process of copper uptake as observed for the
      double mutant may be relevant for a better understanding of the way copper
      chaperones accept and transfer metal ions in the living cell.

PMID- 12186860
TI  - Alterations in thin filament regulation induced by a human cardiac troponin T
      mutant that causes dilated cardiomyopathy are distinct from those induced by
      troponin T mutants that cause hypertrophic cardiomyopathy.
AB  - We have compared the in vitro regulatory properties of recombinant human cardiac
      troponin reconstituted using wild type troponin T with troponin containing the
      DeltaLys-210 troponin T mutant that causes dilated cardiomyopathy (DCM) and the
      R92Q troponin T known to cause hypertrophic cardiomyopathy (HCM). Troponin
      containing DeltaLys-210 troponin T inhibited actin-tropomyosin-activated myosin
      subfragment-1 ATPase activity to the same extent as wild type at pCa8.5 (>80%)
      but produced substantially less enhancement of ATPase at pCa4.5. The Ca(2+)
      sensitivity of ATPase activation was increased (DeltapCa(50) = +0.2 pCa units)
      and cooperativity of Ca(2+) activation was virtually abolished. Equimolar
      mixtures of wild type and DeltaLys-210 troponin T gave a lower Ca(2+) sensitivity
      than with wild type, while maintaining the diminished ATPase activation at pCa4.5
      observed with 100% mutant. In contrast, R92Q troponin gave reduced inhibition at
      pCa8.5 but greater activation than wild type at pCa4.5; Ca(2+) sensitivity was
      increased but there was no change in cooperativity. In vitro motility assay of
      reconstituted thin filaments confirmed the ATPase results and moreover indicated
      that the predominant effect of the DeltaLys-210 mutation was a reduced sliding
      speed. The functional consequences of this DCM mutation are qualitatively
      different from the R92Q or any other studied HCM troponin T mutation, suggesting
      that DCM and HCM may be triggered by distinct primary stimuli.

PMID- 12186861
TI  - Using functional domain composition and support vector machines for prediction of
      protein subcellular location.
AB  - Proteins are generally classified into the following 12 subcellular locations: 1)
      chloroplast, 2) cytoplasm, 3) cytoskeleton, 4) endoplasmic reticulum, 5)
      extracellular, 6) Golgi apparatus, 7) lysosome, 8) mitochondria, 9) nucleus, 10)
      peroxisome, 11) plasma membrane, and 12) vacuole. Because the function of a
      protein is closely correlated with its subcellular location, with the rapid
      increase in new protein sequences entering into databanks, it is vitally
      important for both basic research and pharmaceutical industry to establish a high
      throughput tool for predicting protein subcellular location. In this paper, a new
      concept, the so-called "functional domain composition" is introduced. Based on
      the novel concept, the representation for a protein can be defined as a vector in
      a high-dimensional space, where each of the clustered functional domains derived
      from the protein universe serves as a vector base. With such a novel
      representation for a protein, the support vector machine (SVM) algorithm is
      introduced for predicting protein subcellular location. High success rates are
      obtained by the self-consistency test, jackknife test, and independent dataset
      test, respectively. The current approach not only can play an important
      complementary role to the powerful covariant discriminant algorithm based on the
      pseudo amino acid composition representation (Chou, K. C. (2001) Proteins Struct.
      Funct. Genet. 43, 246-255; Correction (2001) Proteins Struct. Funct. Genet. 44,
      60), but also may greatly stimulate the development of this area.

PMID- 12186862
TI  - Characterization of an osteoblast-specific enhancer element in the CBFA1 gene.
AB  - Cbfa1 is a critical regulator of cell differentiation expressed only in the
      osteochondrogenic lineage. To define the molecular basis of this cell-specific
      expression we analyzed the murine Cbfa1 promoter. Here we show that the first 976
      bp of this promoter are specifically active in osteoblastic cells. Within this
      region DNase I footprinting delineated a 40-bp area (CE1) protected differently
      by nuclear extracts from osteoblastic cells and from non-osteoblastic cells. When
      multimerized, CE1 conferred an osteoblast-specific activity to a heterologous
      promoter in DNA transfection experiments; this enhancing ability was conserved
      between mouse, rat, and human CE1 present in the respective Cbfa1 promoters. CE1
      site-specific mutagenesis determined that it binds NF1- and AP1-like activities.
      Further analyses revealed that the NF1 site acts as a repressor in non
      osteoblastic cells due to the binding of NF1-A, a NF1 isoform not expressed in
      osteoblastic cells. In contrast, the AP1 site mediates an osteoblast-specific
      activation caused by the preferential binding of FosB to CE1 in osteoblastic
      cells. In summary, this study identified an osteoblast-specific enhancer in the
      Cbfa1 promoter whose activity is achieved by the combination of an inhibitory and
      an activatory mechanism.

PMID- 12186863
TI  - A role for protein phosphatase-2A in p38 mitogen-activated protein kinase
      mediated regulation of the c-Jun NH(2)-terminal kinase pathway in human
      neutrophils.
AB  - Human neutrophil accumulation in inflammatory foci is essential for the effective
      control of microbial infections. Although exposure of neutrophils to cytokines
      such as tumor necrosis factor-alpha (TNFalpha), generated at sites of
      inflammation, leads to activation of MAPK pathways, mechanisms responsible for
      the fine regulation of specific MAPK modules remain unknown. We have previously
      demonstrated activation of a TNFalpha-mediated JNK pathway module, leading to
      apoptosis in adherent human neutrophils (Avdi, N. J., Nick, J. A., Whitlock, B.
      B., Billstrom, M. A., Henson, P. M., Johnson, G. L., and Worthen, G. S. (2001) J.
      Biol. Chem. 276, 2189-2199). Herein, evidence is presented linking regulation of
      the JNK pathway to p38 MAPK and the Ser/Thr protein phosphatase-2A (PP2A).
      Inhibition of p38 MAPK by SB 203580 and M 39 resulted in significant augmentation
      of TNFalpha-induced JNK and MKK4 (but not MKK7 or MEKK1) activation, whereas
      prior exposure to a p38-activating agent (platelet-activating factor) diminished
      the TNFalpha-induced JNK response. TNFalpha-induced apoptosis was also greatly
      enhanced upon p38 inhibition. Studies with a reconstituted cell-free system
      indicated the absence of a direct inhibitory effect of p38 MAPK on the JNK
      module. Neutrophil exposure to the Ser/Thr phosphatase inhibitors okadaic acid
      and calyculin A induced JNK activation. Increased phosphatase activity following
      TNFalpha stimulation was shown to be PP2A-associated and p38-dependent.
      Furthermore, PP2A-induced dephosphorylation of MKK4 resulted in its inactivation.
      Thus, in neutrophils, p38 MAPK, through a PP2A-mediated mechanism, regulates the
      JNK pathway, thus determining the extent and nature of subsequent responses such
      as apoptosis.

PMID- 12186864
TI  - Feedback inhibition and product complexes of recombinant mouse muscle
      adenylosuccinate synthetase.
AB  - Adenylosuccinate synthetase governs the committed step of AMP biosynthesis, the
      generation of 6-phosphoryl-IMP from GTP and IMP followed by the formation of
      adenylosuccinate from 6-phosphoryl-IMP and l-aspartate. The enzyme is subject to
      feedback inhibition by AMP and adenylosuccinate, but crystallographic complexes
      of the mouse muscle synthetase presented here infer mechanisms of inhibition that
      involve potentially synergistic ligand combinations. AMP alone adopts the
      productive binding mode of IMP and yet stabilizes the active site in a
      conformation that favors the binding of Mg(2+)-IMP to the GTP pocket. On the
      other hand, AMP, in the presence of GDP, orthophosphate, and Mg(2+), adopts the
      binding mode of adenylosuccinate. Depending on circumstances then, AMP behaves as
      an analogue of IMP or as an analogue of adenylosuccinate. The complex of
      adenylosuccinate.GDP.Mg(2+).sulfate, the first structure of an adenylosuccinate
      bound synthetase, reveals significant geometric distortions and tight nonbonded
      contacts relevant to the proposed catalytic mechanism. Adenylosuccinate forms
      from 6-phosphoryl-IMP and l-aspartate by the movement of the purine ring into the
      alpha-amino group of l-aspartate.

PMID- 12186865
TI  - Dimension, shape, and conformational flexibility of a two domain fungal cellulase
      in solution probed by small angle X-ray scattering.
AB  - Cellulase Cel45 from Humicola insolens has a modular structure with a catalytic
      module and a cellulose-binding module (CBM) separated by a 36 amino acid,
      glycosylated, linker peptide. The solution conformation of the entire two domain
      Cel45 protein as well as the effect of the length and flexibility of the linker
      on the spatial arrangement of the constitutive modules were studied by small
      angle x-ray scattering combined with the known three-dimensional structure of the
      individual modules. The measured dimensions of the enzyme show that the linker
      exhibits an extended conformation leading to a maximum extension between the two
      centers of mass of each module corresponding to about four cellobiose units on a
      cellulose chain. The glycosylation of the linker is the key factor defining its
      extended conformation, and a five proline stretch mutation on the linker was
      found to confer a higher rigidity to the enzyme. Our study shows that the
      respective positioning of the catalytic module and the CBM onto the insoluble
      substrate is most likely influenced by the linker structure and flexibility. Our
      results are consistent with a model where cellulases can move on the surface of
      cellulose with a caterpillar-like displacement with free energy restrictions.

PMID- 12186866
TI  - Reaction of reduced flavins and flavoproteins with diphenyliodonium chloride.
AB  - The reaction of diphenyliodonium chloride with free reduced flavins has been
      studied by stopped flow spectrophotometry under anaerobic conditions, and second
      order rate constants were determined as a function of pH. The reactive flavin
      species was identified as the reduced anion, based on an observed reaction pK of
      6.7. The product mixture was independent of the initial concentration of reactant
      and contained approximately 20% oxidized flavin. The results can be modeled
      quantitatively on a modification of the mechanism proposed by Tew (Tew, D. G.
      (1993) Biochemistry 32, 10209-10215). The composition of the complex reaction
      mixture has been analyzed, and four flavin-phenyl adducts with distinctive
      absorbance and fluorescence characteristics have been identified, involving
      substitution at the flavin C4a, N5, and C8 positions. Inactivation of
      flavoprotein enzymes by diphenyliodonium has also been studied, and several
      examples were found where inactivation occurs readily, despite noninvolvement of
      radical intermediates in their reaction mechanisms. It can be concluded that
      inactivation by phenyliodonium species is not a valid indicator of catalytic
      mechanism involving radical intermediates. One of the several factors determining
      inactivation is maintenance of the enzyme flavin in the reduced form in the
      steady state of catalysis, the other factors being redox potential and
      accessibility of the inhibitor to the flavin active site.

PMID- 12186867
TI  - Cooperativity and flexibility of cystic fibrosis transmembrane conductance
      regulator transmembrane segments participate in membrane localization of a
      charged residue.
AB  - Polytopic protein topology is established in the endoplasmic reticulum (ER) by
      sequence determinants encoded throughout the nascent polypeptide. Here we
      characterize 12 topogenic determinants in the cystic fibrosis transmembrane
      conductance regulator, and identify a novel mechanism by which a charged residue
      is positioned within the plane of the lipid bilayer. During cystic fibrosis
      transmembrane conductance regulator biogenesis, topology of the C-terminal
      transmembrane domain (TMs 7-12) is directed by alternating signal (TMs 7, 9, and
      11) and stop transfer (TMs 8, 10, and 12) sequences. Unlike conventional stop
      transfer sequences, however, TM8 is unable to independently terminate
      translocation due to the presence of a single charged residue, Asp(924), within
      the TM segment. Instead, TM8 stop transfer activity is specifically dependent on
      TM7, which functions both to initiate translocation and to compensate for the
      charged residue within TM8. Moreover, even in the presence of TM7, the N terminus
      of TM8 extends significantly into the ER lumen, suggesting a high degree of
      flexibility in establishing TM8 transmembrane boundaries. These studies
      demonstrate that signal sequences can markedly influence stop transfer behavior
      and indicate that ER translocation machinery simultaneously integrates
      information from multiple topogenic determinants as they are presented in rapid
      succession during polytopic protein biogenesis.

PMID- 12186868
TI  - Down-regulation of human type II collagen gene expression by transforming growth
      factor-beta 1 (TGF-beta 1) in articular chondrocytes involves SP3/SP1 ratio.
AB  - Although transforming growth factor beta1 (TGF-beta1) is generally considered as
      a stimulator of type I collagen production in smooth organs, we found that it can
      inhibit type II collagen biosynthesis in primary rabbit articular chondrocytes
      (RAC) at transcriptional levels. Constructs of promoter and first intron
      sequences associated with the luciferase reporter gene were used to delineate the
      gene sequences involved in TGF-beta1 control of human COL2A1 gene transcription.
      Cotransfection of these DNA fragments with a TbetaRII/I cDNA hybrid receptor,
      capable of inducing a TGF-beta1 dominant negative effect, showed that TGF-beta1
      inhibits specifically COL2A1 gene transcription in RAC by a 63-bp proximal
      promoter. Footprint and gel retardation analyses revealed that the TGF-beta1
      induced inhibition effect exerted through the 63-bp promoter sequence implies a
      multimeric complex that binds to the -41/-33 sequence and involves Sp1 and Sp3
      transcription factors. Transfection of decoy Sp-binding oligonucleotides
      corroborated the implication of the proximal promoter in the TGF-beta1-induced
      inhibition of COL2A1 gene transcription. In addition, TGF-beta1 was found to
      increase the expression of Sp3 without significant changes to its binding level,
      but repressed both the biosynthesis and binding activity of Sp1. In functional
      assays, Sp3 inhibited the 63-bp promoter activity and prevented Sp1 induction of
      transcription. These findings suggest that TGF-beta1 inhibition of COL2A1 gene
      transcription in RAC is mediated by an increase of the Sp3/Sp1 ratio and by the
      repression of Sp1 transactivating effects on that gene.

PMID- 12186869
TI  - Structure of the N-linked glycan present on multiple glycoproteins in the Gram
      negative bacterium, Campylobacter jejuni.
AB  - Mass spectrometry investigations of partially purified Campylobacter jejuni
      protein PEB3 showed it to be partially modified with an Asn-linked glycan with a
      mass of 1406 Da and composed of one hexose, five N-acetylhexosamines and a
      species of mass 228 Da, consistent with a trideoxydiacetamidohexose. By means of
      soybean lectin affinity chromatography, a mixture of glycoproteins was obtained
      from a glycine extract, and two-dimensional gel proteomics analysis led to the
      identification of at least 22 glycoproteins, predominantly annotated as
      periplasmic proteins. Glycopeptides were prepared from the glycoprotein mixture
      by Pronase digestion and gel filtration. The structure of the glycan was
      determined by using nano-NMR techniques to be GalNAc-alpha1,4-GalNAc-alpha1,4
      [Glcbeta1,3-]GalNAc-alpha1,4-GalNAc-alpha1,4-GalNAc-alpha1,3-Bac-beta1,N-Asn-Xaa,
      where Bac is bacillosamine, 2,4-diacetamido-2,4,6-trideoxyglucopyranose. Protein
      glycosylation was abolished when the pglB gene was mutated, providing further
      evidence that the enzyme encoded by this gene is responsible for formation of the
      glycopeptide N-linkage. Comparison of the pgl locus with that of Neisseria
      meningitidis suggested that most of the homologous genes are probably involved in
      the biosynthesis of bacillosamine.

PMID- 12186870
TI  - Crystal structure of a complex formed between a snake venom phospholipase A(2)
      and a potent peptide inhibitor Phe-Leu-Ser-Tyr-Lys at 1.8 A resolution.
AB  - Phospholipase A(2) is an important enzyme involved in the production of
      prostaglandins and their related compounds causing inflammatory disorders. Among
      the several peptides tested, the peptide Phe-Leu-Ser-Tyr-Lys (FLSYK) showed the
      highest inhibition. The dissociation constant (K(d)) for this peptide was
      calculated to be 3.57 +/- 0.05 x 10(-9) m. In order to further improve the degree
      of inhibition of phospholipase A(2), a complex between Russells viper snake venom
      phospholipase A(2) and a peptide inhibitor FLSYK was crystallized, and its
      structure was determined by crystallographic methods and refined to an R-factor
      of 0.205 at 1.8 A resolution. The structure contains two crystallographically
      independent molecules of phospholipase A(2) (molecules A and B) and a peptide
      molecule specifically bound to molecule A only. The two molecules formed an
      asymmetric dimer. The dimerization caused a modification in the binding site of
      molecule A. The overall conformations of molecules A and B were found to be
      generally similar except three regions i.e. the Trp-31-containing loop (residues
      25-34), the beta-wing consisting of two antiparallel beta-strands (residues 74
      85) and the C-terminal region (residues 119-133). Out of the above three, the
      most striking difference pertains to the conformation of Trp-31 in the two
      molecules. The orientation of Trp-31 in molecule A was suitable for the binding
      of FLSYK, while it disallowed the binding of peptide to molecule B. The structure
      of the complex clearly shows that the peptide is so placed in the binding site of
      molecule A that the side chain of its lysine residue interacted extensively with
      the enzyme and formed several hydrogen bonds in addition to a strong
      electrostatic interaction with critical Asp-49. The C-terminal carboxylic group
      of the peptide interacted with the catalytic residue His-48.

PMID- 12186871
TI  - Charged amino acids in the sixth transmembrane helix of multidrug resistance
      protein 1 (MRP1/ABCC1) are critical determinants of transport activity.
AB  - The multidrug resistance protein, MRP1 (ABCC1), is an ATP-binding cassette
      transporter that confers resistance to chemotherapeutic agents. MRP1 also
      mediates transport of organic anions such as leukotriene C(4) (LTC(4)), 17beta
      estradiol 17-(beta-d-glucuronide) (E(2)17betaG), estrone 3-sulfate, methotrexate
      (MTX), and GSH. We replaced three charged amino acids, Lys(332), His(335), and
      Asp(336), predicted to be in the sixth transmembrane (TM6) helix of MRP1 with
      neutral and oppositely charged amino acids and determined the effect on substrate
      specificity and transport activity. All mutants were expressed in transfected
      human embryonic kidney cells at levels comparable with wild-type MRP1, and
      confocal microscopy showed that they were correctly routed to the plasma
      membrane. Vesicular transport studies revealed that the MRP1-Lys(332) mutants had
      lost the ability to transport LTC(4), and GSH transport was reduced; whereas
      E(2)17betaG, estrone 3-sulfate, and MTX transport were unaffected. E(2)17betaG
      transport was not inhibited by LTC(4) and could not be photolabeled with
      [(3)H]LTC(4), indicating that the MRP1-Lys(332) mutants no longer bound this
      substrate. Substitutions of MRP1-His(335) also selectively diminished LTC(4)
      transport and photolabeling but to a lesser extent. Kinetic analyses showed that
      V(max) (LTC(4)) of these mutants was decreased but K(m) was unchanged. In
      contrast to the selective loss of LTC(4) transport in the Lys(332) and His(335)
      mutants, the MRP1-Asp(336) mutants no longer transported LTC(4), E(2)17betaG,
      estrone 3-sulfate, or GSH, and transport of MTX was reduced by >50%. Lys(332),
      His(335), and Asp(336) of TM6 are predicted to be in the outer leaflet of the
      membrane and are all capable of forming intrahelical and interhelical ion pairs
      and hydrogen bonds. The importance of Lys(332) and His(335) in determining
      substrate specificity and of Asp(336) in overall transport activity suggests that
      such interactions are critical for the binding and transport of LTC(4) and other
      substrates of MRP1.

PMID- 12186872
TI  - Repression of DAX-1 and induction of SF-1 expression. Two mechanisms contributing
      to the activation of aldosterone biosynthesis in adrenal glomerulosa cells.
AB  - Angiotensin II (Ang II) and adrenocorticotropic hormone stimulate aldosterone
      biosynthesis in the zona glomerulosa of the adrenal cortex through induction of
      the expression of the steroidogenic acute regulatory (StAR) protein, which
      promotes intramitochondrial cholesterol transfer. To understand the mechanism of
      this induction of the StAR protein, we have examined the effect of Ang II and
      forskolin, a mimicker of adrenocorticotropic hormone action, on two transcription
      factors known to modulate StAR gene expression in opposite ways, DAX-1 and SF-1,
      in bovine adrenal glomerulosa cells in primary culture. Ang II markedly inhibited
      DAX-1 protein expression in a time- and concentration-dependent manner (to 38.7
      +/- 12.9% of controls at 3 nm after 6 h, p < 0.01), an effect that required de
      novo protein synthesis and ERK2/1 activation. This effect was associated with a
      concomitant decrease in DAX-1 mRNA and an increase in mitochondrial StAR protein
      levels. Similarly, forskolin dramatically repressed DAX-1 protein and mRNA
      expression (to 19.6 +/- 1.8 and 50.3 +/- 4.7% of controls, respectively, p <
      0.01). Neither Ang II nor forskolin affected DAX-1 protein and mRNA stability.
      The aldosterone response to Ang II was markedly reduced (to 59 +/- 4% of
      controls, p < 0.01) in transiently transfected cells overexpressing DAX-1.
      Whereas Ang II was without effect on SF-1 expression, forskolin significantly
      increased SF-1 protein and mRNA levels in a cycloheximide-sensitive manner (to
      167.4 +/- 16.6 and 173.1 +/- 25.1% of controls after 6 h, respectively, p <
      0.01). These results demonstrate that the balance between repressor and inducer
      function of DAX-1 and SF-1 are of critical importance in the regulation of
      adrenal aldosterone biosynthesis.

PMID- 12186873
TI  - Major conformational changes occur during the transition from an initiation
      complex to an elongation complex by T7 RNA polymerase.
AB  - To examine changes that occur during the transition from an initiation complex
      (IC) to an elongation complex (EC) in T7 RNA polymerase (RNAP), we used nucleic
      acid-protein cross-linking methods to probe interactions of the RNAP with RNA and
      DNA in a halted EC. As the RNA is displaced from the RNA-DNA hybrid approximately
      9 bp upstream from the active site (at -9) it interacts with a region within the
      specificity loop (residues 744-750) and is directed toward a positively charged
      surface that surrounds residues Lys-302 and Lys-303. Surprisingly, the template
      and non-template strands of the DNA at the upstream edge of the hybrid (near the
      site where the RNA is displaced) interact with a region in the N-terminal domain
      of the RNAP (residues 172-191) that is far away from the specificity loop before
      isomerization (in the IC). To bring these two regions of the RNAP into proximity,
      major conformational changes must occur during the transition from an IC to an
      EC. The observed nucleic acid-protein interactions help to explain the behavior
      of a number of mutant RNAPs that are affected at various stages in the initiation
      process and in termination.

PMID- 12186874
TI  - New roles for conserved regions within a sigma 54-dependent enhancer-binding
      protein.
AB  - 23 amino acid substitutions were made in the C7 and C3 regions of pspFDeltaHTH, a
      protein required to convert sigma(54) closed promoter complexes to open
      complexes. These mutants were assayed for transcriptional competence, for the
      ability to hydrolyze ATP, for their multimerization state, and for their ability
      to interact with sigma(54) and its holoenzyme. C7 region mutants caused the
      protein to assume a compact form. This property could be mimicked by the addition
      of ATP, implying that compaction via C7 and ATP is part of the activation
      process. A number of C3 mutants were important for energy coupling, as indicated
      previously for several members of this activator family (, ). However, a patch
      within C3 influenced oligomerization. The C3 region was especially important in
      interacting with sigma(54) during the transition state but not important in
      inducing sigma(54) holoenzyme to engage the nontemplate strand of the promoter.
      It is proposed that both regions contain deterrent functions that prevent
      premature activation. Overall, the results imply unexpected roles for the C7 and
      C3 regions of this protein family during promoter activation.

PMID- 12186875
TI  - Role of prolyl hydroxylation in oncogenically stabilized hypoxia-inducible factor
      1alpha.
AB  - Stabilization of the hypoxia-inducible factor-1 (HIF-1) protein is essential for
      its role as a regulator of gene expression under low oxygen conditions. Here,
      employing a novel hydroxylation-specific antibody, we directly show that proline
      564 of HIF-1alpha and proline 531 of HIF-2alpha are hydroxylated under normoxia.
      Importantly, HIF-1alpha Pro-564 and HIF-2alpha Pro-531 hydroxylation is
      diminished with the treatment of hypoxia, cobalt chloride, desferrioxamine, or
      dimethyloxalyglycine, regardless of the E3 ubiquitin ligase activity of the von
      Hippel-Lindau (VHL) tumor suppressor gene. Furthermore, in VHL-deficient cells,
      HIF-1alpha Pro-564 and HIF-2alpha Pro-531 had detectable amounts of hydroxylation
      following transition to hypoxia, indicating that the post-translational
      modification is not reversible. The introduction of v-Src or RasV12 oncogenes
      resulted in the stabilization of normoxic HIF-1alpha and the loss of hydroxylated
      Pro-564, demonstrating that oncogene-induced stabilization of HIF-1alpha is
      signaled through the inhibition of prolyl hydroxylation. Conversely, a
      constitutively active Akt oncogene stabilized HIF-1alpha under normoxia
      independently of prolyl hydroxylation, suggesting an alternative mechanism for
      HIF-1alpha stabilization. Thus, these results indicate distinct pathways for HIF
      1alpha stabilization by different oncogenes. More importantly, these findings
      link oncogenesis with normoxic HIF-1alpha expression through prolyl
      hydroxylation.

PMID- 12186876
TI  - A nonpermeant biotin derivative gains access to the parasitophorous vacuole in
      Plasmodium falciparum-infected erythrocytes permeabilized with streptolysin O.
AB  - In its host erythrocyte, the malaria parasite Plasmodium falciparum resides
      within a parasitophorous vacuole, the membrane of which forms a barrier between
      the host cell cytosol and the parasite surface. The vacuole is a unique
      compartment because it contains specific proteins that are believed to be
      involved in cell biological functions essential for parasite survival. As a
      prerequisite for the characterization of the vacuolar proteome, we have developed
      an experimental approach that allows the selective biotinylation of soluble
      vacuolar proteins. This approach utilizes nonpermeant biotin derivatives that can
      be introduced into infected erythrocytes after selective permeabilization of the
      erythrocyte membrane with the pore-forming protein streptolysin O. The
      derivatives gain access to the vacuolar lumen but not to the parasite cytosol,
      thus providing supportive evidence for the existence of nonselective pores within
      the vacuolar membrane that have been postulated based on electrophysiological
      studies. Soluble vacuolar proteins that are biotin-labeled can be isolated by
      affinity chromatography using streptavidin-agarose.

PMID- 12186877
TI  - Transcriptional induction of mitogen-activated protein kinase phosphatase 1 by
      retinoids. Selective roles of nuclear receptors and contribution to the
      antiapoptotic effect.
AB  - All-trans-retinoic acid (t-RA) inhibits hydrogen peroxide (H(2)O(2))-induced
      apoptosis by inhibiting the c-Jun N-terminal kinase (JNK)-activator protein 1 (AP
      1) pathway. In this report, we examined the involvement of mitogen-activated
      protein kinase phosphatase 1 (MKP-1) in suppression of JNK and the antiapoptotic
      effect of t-RA and the roles of nuclear receptors in the regulation of MKP-1 by t
      RA. We found that not only t-RA, but also a selective agonist of retinoic acid
      receptor (RAR), a selective agonist of retinoid X receptor (RXR), and a pan
      agonist of RAR and RXR all induced MKP-1 at the transcriptional level. Activation
      of RAR was required for all of these triggering effects, but activation of RXR
      was required only for the RXR agonist-induced MKP-1 expression. Among the three
      RAR subtypes, RARalpha and RARgamma, but not RARbeta, mediated the t-RA-induced
      MKP-1 expression. The antiapoptotic effect of t-RA on H(2)O(2)-induced apoptosis
      in several cell types was correlated with the inducibility of MKP-1 by t-RA.
      Inhibition of MKP-1 by vanadate enhanced JNK phosphorylation and attenuated the
      antiapoptotic effect of t-RA. Furthermore, overexpression of MKP-1 inhibited
      H(2)O(2)-induced JNK phosphorylation and apoptosis. To our knowledge, this is the
      first to demonstrate that 1) MKP-1 is inducible by retinoids at the
      transcriptional level, 2) RXR and individual RAR subtypes have different roles in
      this process, and 3) the induced MKP-1 plays a significant role in mediating both
      JNK inhibition and the antiapoptotic effect of t-RA in oxidative stress.

PMID- 12186878
TI  - Homologous and heterologous inhibitory effects of ATPase inhibitor proteins on F
      ATPases.
AB  - In Saccharomyces cerevisiae, at least three proteins (IF(1), STF(1), and STF(2))
      appear to be involved in the regulation of ATP synthase. Both IF(1) and STF(1)
      inhibit F(1), whereas the proposed function for STF(2) is to facilitate the
      binding of IF(1) and STF(1) to F(1). The oligomerization properties of yeast
      IF(1) and STF(1) have been investigated by sedimentation equilibrium analytical
      ultracentrifugation and by covalent cross-linking. Both techniques confirm that
      IF(1) and STF(1) oligomerize in opposite directions in relation to pH, suggesting
      that both proteins might regulate yeast F(1)F(0)-ATPase under different
      conditions. Their effects on bovine F-ATPases are also described. Whereas bovine
      IF(1) inhibits yeast F(1)-ATPase even better than yeast IF(1) or STF(1), the
      capability of yeast IF(1) to inhibit the bovine enzyme is very low and decreases
      with time. Such an effect is also observed in the study of the homologous
      inhibition of yeast F(1)-ATPase. Yeast inhibitors are not as effective as their
      bovine counterpart, and the complex seems to dissociate gradually.

PMID- 12186879
TI  - Concanamycin A, the specific inhibitor of V-ATPases, binds to the V(o) subunit c.
AB  - Vacuolar-type ATPase (V-ATPase) purified from the midgut of the tobacco hornworm
      Manduca sexta is inhibited 50% by 10 nm of the plecomacrolide concanamycin A, the
      specific inhibitor of V-ATPases. To determine the binding site(s) of that
      antibiotic in the enzyme complex, labeling with the semisynthetic 9-O-[p
      (trifluoroethyldiazirinyl)-benzoyl]-21,23-dideoxy-23-[(125)I]iodo-concanolide A
      (J-concanolide A) was performed, which still inhibits the V-ATPase 50% at a
      concentration of 15-20 microm. Upon treatment with UV light, a highly reactive
      carbene is generated from this concanamycin derivative, resulting in the
      formation of a covalent bond to the enzyme. In addition, the radioactive tracer
      (125)I makes the detection of the labeled subunit(s) feasible. Treatment of the
      V(1)/V(o) holoenzyme, the V(o) complex, and the V-ATPase containing goblet cell
      apical membranes with concanolide resulted in the labeling of only the
      proteolipid, subunit c, of the proton translocating V(o) complex. Binding of J
      concanolide A to subunit c was prevented in a concentration-dependent manner by
      concanamycin A, indicating that labeling was specific. Binding was also prevented
      by the plecomacrolides bafilomycin A(1) and B(1), respectively, but not by the
      benzolactone enamide salicylihalamide, a member of a novel class of V-ATPase
      inhibitors.

PMID- 12186880
TI  - Stereospecificity and kinetic mechanism of human prenylcysteine lyase, an unusual
      thioether oxidase.
AB  - Prenylated proteins contain either a 15-carbon farnesyl or a 20-carbon
      geranylgeranyl isoprenoid covalently attached to cysteine residues at or near
      their C terminus. The cellular abundance of prenylated proteins, as well as the
      stability of the thioether bond, poses a metabolic challenge to cells. A
      lysosomal enzyme termed prenylcysteine lyase has been identified that degrades a
      variety of prenylcysteines. Prenylcysteine lyase is a FAD-dependent thioether
      oxidase that produces free cysteine, an isoprenoid aldehyde, and hydrogen
      peroxide as products of the reaction. Here we report initial studies of the
      kinetic mechanism and stereospecificity of this unusual enzyme. We utilized
      product and dead end inhibitors of prenylcysteine lyase to probe the kinetic
      mechanism of the multistep reaction. The results with these inhibitors, together
      with those of other experiments, suggest that the reaction catalyzed by
      prenylcysteine lyase proceeds through a sequential mechanism. The reaction
      catalyzed by the enzyme is stereospecific, in that the pro-S hydride of the
      farnesylcysteine is transferred to FAD to initiate the reaction. With (2R,1'S)
      [1'-(2)H(1)]farnesylcysteine as a substrate, a primary deuterium isotope effect
      of 2 was observed on the steady state rate. However, the absence of an isotope
      effect on an observed pre-steady-state burst of hydrogen peroxide formation
      implicates a partially rate-determining proton transfer after a relatively fast C
      H (C-D) bond cleavage step. Furthermore, no pre-steady-state burst of cysteine
      was observed. The finding that the rate of cysteine formation was within 2-fold
      of the steady-state k(cat) value indicates that cysteine production is one of the
      primary rate-limiting steps in the reaction. These results provide substantial
      new information on the catalytic mechanism of prenylcysteine lyase.

PMID- 12186881
TI  - Structural biology of bacterial multidrug resistance gene regulators.

PMID- 12186882
TI  - Inhibition of beta interferon transcription by noncytopathogenic bovine viral
      diarrhea virus is through an interferon regulatory factor 3-dependent mechanism.
AB  - The induction and inhibition of the interferon (IFN) response and apoptosis by
      bovine viral diarrhea virus (BVDV) has been examined. Here we show that prior
      infection of cells by noncytopathogenic BVDV (ncp BVDV) fails to block
      transcriptional responses to alpha/beta IFN. In contrast, ncp BVDV-infected cells
      fail to produce IFN-alpha/beta or MxA in response to double-stranded RNA (dsRNA)
      or infection with a heterologous virus (Semliki Forest virus [SFV]). ncp BVDV
      preinfection is unable to block cp BVDV- or SFV-induced apoptosis. The effects of
      ncp BVDV infection on the transcription factors controlling the IFN-beta
      induction pathway have been analyzed. The transcription factor NF-kappa B was not
      activated following ncp BVDV infection, but ncp BVDV infection was not able to
      block the activation of NF-kappa B by either SFV or tumor necrosis factor alpha.
      Furthermore, ncp BVDV infection did not result in the activation of stress
      kinases (JNK1 and JNK2) or the phosphorylation of transcription factors ATF-2 and
      c-Jun; again, ncp BVDV infection was not able to block their activation by SFV.
      Interferon regulatory factor 3 (IRF-3) was shown to be translocated to the nuclei
      of infected cells in response to ncp BVDV, although DNA-binding of IRF-3 was not
      seen in nuclear extracts. In contrast, an IRF-3-DNA complex was observed in
      nuclear extracts from cells infected with SFV, but the appearance of this complex
      was blocked when cells were previously exposed to ncp BVDV. We conclude that the
      inhibition of IFN induction by this pestivirus involves a block to IRF-3
      function, and we speculate that this may be a key characteristic for the survival
      of pestiviruses in nature.

PMID- 12186883
TI  - A single amino acid mutation in the PA subunit of the influenza virus RNA
      polymerase inhibits endonucleolytic cleavage of capped RNAs.
AB  - The influenza A virus RNA-dependent RNA polymerase consists of three subunits
      PB1, PB2, and PA. The PB1 subunit is the catalytically active polymerase,
      catalyzing the sequential addition of nucleotides to the growing RNA chain. The
      PB2 subunit is a cap-binding protein that plays a role in initiation of viral
      mRNA synthesis by recruiting capped RNA primers. The function of PA is unknown,
      but previous studies of temperature-sensitive viruses with mutations in PA have
      implied a role in viral RNA replication. In this report we demonstrate that the
      PA subunit is required not only for replication but also for transcription of
      viral RNA. We mutated evolutionarily conserved amino acids to alanines in the C
      terminal region of the PA protein, since the C-terminal region shows the highest
      degree of conservation between PA proteins of influenza A, B, and C viruses. We
      tested the effects of these mutations on the ability of RNA polymerase to
      transcribe and replicate viral RNA. We also tested the compatibility of these
      mutations with viral viability by using reverse-genetics techniques. A mutant
      with a histidine-to-alanine change at position 510 (H510A) in the PA protein of
      influenza A/WSN/33 virus showed a differential effect on transcription and
      replication. This mutant was able to perform replication (vRNA-->cRNA-->vRNA),
      but its transcriptional activity (vRNA-->mRNA) was negligible. In vitro analyses
      of the H510A recombinant polymerase, by using transcription initiation, vRNA
      binding, capped-RNA-binding, and endonuclease assays, suggest that the primary
      defect of this mutant polymerase is in its endonuclease activity.

PMID- 12186884
TI  - The immunogenicity and protective efficacy of bovine herpesvirus 1 glycoprotein D
      plus Emulsigen are increased by formulation with CpG oligodeoxynucleotides.
AB  - The immunogenicity and protective efficacy of a bovine herpesvirus 1 (BHV-1)
      subunit vaccine formulated with Emulsigen (Em) and a synthetic
      oligodeoxynucleotide containing unmethylated CpG dinucleotides (CpG ODN) was
      determined in cattle. A truncated, secreted version of BHV-1 glycoprotein D (tgD)
      formulated with Em and CpG ODN at concentrations of 25, 2.5, or 0.25 mg/dose
      produced a more balanced immune response, higher levels of virus neutralizing
      antibodies, and greater protection after BHV-1 challenge compared to tgD
      adjuvanted with either Em or CpG ODN alone. In contrast, tgD formulated with Em
      and either 25 mg of a non-CpG ODN or another immunostimulatory compound, dimethyl
      dioctadecyl ammonium bromide, induced similar immunity and protection compared to
      tgD formulated with Em alone, a finding which confirms the immunostimulatory
      effect of ODN to be CpG motif mediated. Our results demonstrate the ability of
      CpG ODN to induce a strong and balanced immune response in a target species.

PMID- 12186885
TI  - A balanced type 1/type 2 response is associated with long-term nonprogressive
      human immunodeficiency virus type 1 infection.
AB  - Previous reports have emphasized the requirements for strong type 1 cell-mediated
      responses in the control of human immunodeficiency virus type 1 (HIV-1). HIV-1
      Gag p24-specific CD4 helper T-lymphocyte (HTL) responses have been shown to
      inversely correlate with viral burden in HIV-1-infected individuals. In this
      study, peripheral blood mononuclear cells from 70 individuals with chronic
      progressive HIV-1 infection (clinical progressors), 10 clinical nonprogressors,
      and 3 immunologically discordant progressors were assessed for HTL proliferation
      and type 1/type 2 cytokine production. Clinical progressors lacked functional HIV
      1-specific HTLs with proliferative and cytokine-producing capacity. Clinical
      nonprogressors were found to respond to a wide range of HIV-1 antigens from
      different clades, producing both type 1 and type 2 cytokines. Immunologically
      discordant progressors responded strongly to clade B Gag p24 with a type 1
      cytokine profile but not to other antigens. Thus, in contrast to clinical
      nonprogressors, neither progressors nor immunologically discordant progressors
      secreted interleukin-4 (IL-4) in response to HIV-1 antigens. Both clinical
      nonprogressors and immunologically discordant progressors responded broadly to B
      clade Gag p24-overlapping peptides. However, IL-4 production in the
      nonprogressors was restricted to a limited number of p24 peptides. No HIV-1
      specific T-cell responses were seen in 20 seronegative controls. Additionally, we
      observed a rapid type 1 to type 2 shift in the response of one immunologically
      discordant progressor upon onset of clinical symptoms. These results suggest that
      a balanced type 1/type 2 profile correlates with successful long-term control of
      HIV-1.

PMID- 12186886
TI  - Analysis of the complete genome sequence of the Hz-1 virus suggests that it is
      related to members of the Baculoviridae.
AB  - We report the complete sequence of a large rod-shaped DNA virus, called the Hz-1
      virus. This virus persistently infects the Heliothis zea cell lines. The Hz-1
      virus has a double-stranded circular DNA genome of 228,089 bp encoding 154 open
      reading frames (ORFs) and also expresses a persistence-associated transcript 1,
      PAT1. The G+C content of the Hz-1 virus genome is 41.8%, with a gene density of
      one gene per 1.47 kb. Sequence analysis revealed that a 9.6-kb region at 43.6 to
      47.8 map units harbors five cellular genes encoding proteins with homology to
      dUTP pyrophosphatase, matrix metalloproteinase, deoxynucleoside kinase, glycine
      hydroxymethyltransferase, and ribonucleotide reductase large subunit. Other
      cellular homologs were also detected dispersed in the viral genome. Several
      baculovirus homologs were detected in the Hz-1 virus genome. These include PxOrf
      70, PxOrf-29, AcOrf-81, AcOrf-96, AcOrf-22, VLF-1, RNA polymerase LEF-8 (orf50),
      and two structural proteins, p74 and p91. The Hz-1 virus p74 homolog shows high
      structural conservation with a double transmembrane domain at its C terminus.
      Phylogenetic analysis of the p74 revealed that the Hz-1 virus is evolutionarily
      distant from the baculoviruses. Another distinctive feature of the Hz-1 virus
      genome is a gene that is involved in insect development. However, the remainder
      of the ORFs (81%) encoded proteins that bear no homology to any known proteins.
      In conclusion, the sequence differences between the Hz-1 virus and the
      baculoviruses outnumber the similarities and suggest that the Hz-1 virus may form
      a new family of viruses distantly related to the Baculoviridae:

PMID- 12186888
TI  - Ahi-1, a novel gene encoding a modular protein with WD40-repeat and SH3 domains,
      is targeted by the Ahi-1 and Mis-2 provirus integrations.
AB  - The Ahi-1 locus was initially identified as a common helper provirus integration
      site in Abelson pre-B-cell lymphomas and shown to be closely linked to the c-myb
      proto-oncogene. Since no significant alteration of c-myb expression was found in
      Abelson murine leukemia virus-induced pre-B-lymphomas harboring a provirus
      inserted within the Ahi-1 locus, this suggested that it harbors another gene
      whose dysregulation is involved in tumor formation. Here we report the
      identification of a novel gene (Ahi-1) targeted by these provirus insertional
      mutations and the cloning of its cDNA. The Ahi-1 proviral insertions were found
      at the 3' end of the gene, in an inverse transcriptional orientation, with most
      of them located around and downstream of the last exon, whereas another insertion
      was within intron 22. In addition, another previously identified provirus
      insertion site, Mis-2, was found to map within the 16th intron of the Ahi-1 gene.
      The Ahi-1 cDNA encodes a 1,047-amino-acid protein. The predicted Ahi-1 protein is
      a modular protein that contains one SH3 motif and seven WD40 repeats. The Ahi-1
      gene is conserved in mammals and encodes two major RNA species of 5 and 4.2 kb
      and several other shorter splicing variants. The Ahi-1 gene is expressed in mouse
      embryos and in several organs of the mouse and rat, notably at high levels in the
      brain and testes. In tumor cells harboring insertional mutations in Ahi-1,
      truncated Ahi-1/viral fused transcripts were identified, including some splicing
      variants with deletion of the SH3 domain. Therefore, Ahi-1 is a novel gene
      targeted by provirus insertion and encoding a protein that exhibits several
      features of a signaling molecule. Thus, Ahi-1 may play an important role in
      signal transduction in normal cells and may be involved in tumor development,
      possibly in cooperation with other oncogenes (such as v-abl and c-myc) or with a
      tumor suppressor gene (Nf1), since Ahi-1 insertion sites were identified in
      tumors harboring v-abl defective retroviruses or a c-myc transgene or in tumors
      exhibiting deletion of Nf1.

PMID- 12186887
TI  - Human monoclonal antibodies specific for conformation-sensitive epitopes of V3
      neutralize human immunodeficiency virus type 1 primary isolates from various
      clades.
AB  - The epitopes of the V3 domain of the human immunodeficiency virus type 1 (HIV-1)
      gp120 glycoprotein have complex structures consisting of linear and
      conformational antigenic determinants. Anti-V3 antibodies (Abs) recognize both
      types of elements, but Abs which preferentially react to the conformational
      aspect of the epitopes may have more potent neutralizing activity against HIV-1,
      as recently suggested. To test this hypothesis, human anti-V3 monoclonal Abs
      (MAbs) were selected using a V3 fusion protein (V3-FP) which retains the
      conformation of the third variable region. The V3-FP consists of the V3(JR-CSF)
      sequence inserted into a truncated form of murine leukemia virus gp70. Six human
      MAbs which recognize epitopes at the crown of the V3 loop were selected with the
      V3-FP. They were found to react more strongly with molecules displaying
      conformationally intact V3 than with linear V3 peptides. In a virus capture
      assay, these MAbs showed cross-clade binding to native, intact virions of clades
      A, B, C, D, and F. No binding was found to isolates from subtype E. The
      neutralizing activity of MAbs against primary isolates was determined in three
      assays: the GHOST cell assay, a phytohemagglutinin-stimulated peripheral blood
      mononuclear cell assay, and a luciferase assay. While these new MAbs displayed
      various degrees of activity, the pattern of cross-clade neutralization of clades
      A, B, and F was most pronounced. The neutralization of clades C and D viruses was
      weak and sporadic, and neutralization of clade E by these MAbs was not detected.
      Analysis by linear regression showed a highly significant correlation (P <
      0.0001) between the strength of binding of these anti-V3 MAbs to intact virions
      and the percent neutralization. These studies demonstrate that human MAbs to
      conformation-sensitive epitopes of V3 display cross-clade reactivity in both
      binding to native, intact virions and neutralization of primary isolates.

PMID- 12186889
TI  - The antiviral response to gamma interferon.
AB  - A role for alpha/beta interferon (IFN-alpha/beta) in the IFN-gamma antiviral
      response has long been suggested. Accordingly, possible roles for autocrine or
      double-stranded-RNA (dsRNA)-induced IFN-alpha/beta in the IFN-gamma response were
      investigated. Use was made of wild-type and a variety of mutant human
      fibrosarcoma cell lines, including mutant U5A cells, which lack a functional IFN
      alpha/beta receptor and hence an IFN-alpha/beta response. IFN-gamma did not
      induce detectable levels of IFN-alpha/beta in any of the cell lines, nor was the
      IFN-gamma response per se dependent on autocrine IFN-alpha/beta. On the other
      hand, a number of responses to dsRNA [poly(I). poly(C)] and encephalomyocarditis
      virus were greatly enhanced by IFN-gamma pretreatment (priming) of wild-type
      cells or of mutant cells lacking an IFN-alpha/beta response; these include the
      primary induction of dsRNA-inducible mRNAs, including IFN-beta mRNA, and, to a
      lesser extent, the dsRNA-mediated activation of the p38 mitogen-activated protein
      (MAP) kinase(s). IFN-gamma priming of mRNA induction by dsRNA is dependent on
      JAK1 and shows biphasic kinetics, with an initial rapid (<30-min) response being
      followed by a more substantial effect on overnight incubation. The IFN-gamma
      primed dsRNA responses appear to be subject to modulation through the p38,
      phosphatidylinositol 3-kinase, and ERK1/ERK2 MAP kinase pathways. It can be
      concluded that despite efficient priming of IFN-beta production, the IFN
      alpha/beta pathways play no significant role in the primary IFN-gamma antiviral
      response in these cell-virus systems. The observed IFN-gamma priming of dsRNA
      responses, on the other hand, will likely play a significant role in combating
      virus infection in vivo.

PMID- 12186890
TI  - Overexpression of interleukin-2 by a recombinant herpes simplex virus type 1
      attenuates pathogenicity and enhances antiviral immunity.
AB  - The expression of interleukin-2 (IL-2) has been implicated in the modulation of
      the outcome of ocular infection with herpes simplex virus type 1 (HSV-1);
      however, its effects remain controversial. To clarify the role of IL-2, we
      constructed a recombinant HSV-1 (HSV-IL-2) that expresses two copies of the
      murine IL-2 gene under the control of the latency-associated transcript (LAT)
      promoter of HSV-1 in a LAT-negative virus. In tissue culture, the replication of
      the HSV-IL-2 was 100-fold lower than that of the wild-type virus at a low
      multiplicity of infection (MOI). Addition of recombinant anti-IL-2 polyclonal
      antibody markedly enhanced HSV-IL-2 replication in tissue culture. In the 7-day
      period after ocular infection of BALB/c mice, the replication of HSV-IL-2 was
      significantly lower than that of wild-type virus in tear cultures, whole eyes,
      and brain, but was equivalent to wild-type replication in the trigeminal ganglia.
      Ocular challenge of BALB/c mice with HSV-IL-2 alone, at an MOI that resulted in
      only 13% survival when parental virus was used, was associated with 90% survival.
      This decrease in virulence was further shown to be attributable to the expression
      of IL-2 by coinfection of mice with HSV-IL-2 and the parental virus. This
      resulted in a decrease in virulence of the parental virus (5% survival when
      administered alone versus 50% survival on coinfection with HSV-IL-2). The
      survival of HSV-IL-2-infected mice was compromised by depletion of either IL-2,
      CD4(+), or CD8(+) T cells (50% survival) and abolished completely by depletion of
      both T-cell subtypes. Moreover, depletion of CD4(+) T cells, CD8(+) T cells, or
      both increased the titers of HSV-IL-2 in the tears, eyes, trigeminal ganglia, and
      brains of infected mice, so that titers were equivalent to or higher than that of
      the parental virus. These results suggest that IL-2 expression by recombinant HSV
      1 reduces virulence and that depletion of IL-2 or T cells increases virulence in
      HSV-1-infected mice.

PMID- 12186891
TI  - C-Terminal gp40 peptide analogs inhibit feline immunodeficiency virus: cell
      fusion and virus spread.
AB  - The envelope glycoprotein of human immunodeficiency virus type 1 (HIV-1), gp160,
      is synthesized as a protein precursor that when proteolytically cleaved yields
      two subunits, gp120 and gp41. gp120 is the surface glycoprotein on HIV-1
      responsible for binding to CD4, and gp41 is the transmembrane glycoprotein
      involved in the membrane fusion process. gp41 is divided into the N-terminal
      fusion peptide, the heptad repeat 1 (HR1) and HR2 regions, and the C-terminal
      transmembrane region, which are collectively responsible for virus fusion and
      entry into the cell. Synthetic peptides derived from the HR2 and HR1 regions of
      HIV-1(LAI) have been shown to prevent virus-cell fusion and infection in vitro.
      In phase II clinical trials in HIV patients, data revealed that T20 has antiviral
      efficacy and is well tolerated. Similar results were obtained in vitro with HIV-2
      and simian immunodeficiency virus, supporting the conservation of the gp41
      ectodomain among lentiviruses. Feline immunodeficiency virus (FIV) infection in
      the cat has been used as a model to develop potential antivirals for HIV. To
      determine if synthetic gp40 analogs capable of inhibiting FIV infection could be
      identified, 15 overlapping 35-amino-acid peptides derived from the C-terminal HR2
      domain of FIV gp40 were synthesized. These peptides were tested for efficacy
      against FIV in a syncytium-forming assay with FIV-infected CrFK cells and HeLa
      cells expressing the FIV receptor CXCR4. Several peptides exhibited activity at
      the nanogram level. Antiviral activity was confirmed by suppression of reverse
      transcriptase in a FIV feline CD4(+)-T-cell (FCD4-E) acute-infection assay. These
      data demonstrate that synthetic peptides derived from the HR2 domain of the FIV
      gp41 protein are effective inhibitors of FIV infection.

PMID- 12186892
TI  - Characterization of the cis-acting contributions to avian hepadnavirus RNA
      encapsidation.
AB  - Previous analysis of duck hepatitis B virus (DHBV) indicated the presence of at
      least two cis-acting sequences required for efficient encapsidation of its
      pregenomic RNA (pgRNA), epsilon and region II. epsilon, an RNA stem-loop near the
      5' end of the pgRNA, has been characterized in detail, while region II, located
      in the middle of the pgRNA, is not as well defined. Our initial aim was to
      identify the sequence important for the function of region II in DHBV. We scanned
      region II and the surrounding sequence by using a quantitative encapsidation
      assay. We found that the sequence between nucleotides (nt) 438 and 720
      contributed to efficient pgRNA encapsidation, while the sequence between nt 538
      and 610 made the largest contribution to encapsidation. Additionally, deletions
      between the two encapsidation sequences, epsilon and region II, had variable
      effects on encapsidation, while substitutions of heterologous sequence between
      epsilon and region II disrupted the ability of the pgRNA to be encapsidated
      efficiently. Overall, these data indicate that the intervening sequences between
      epsilon and region II play a role in encapsidation. We also analyzed heron
      hepatitis B virus (HHBV) for the presence of region II and found features similar
      to DHBV: a broad region necessary for efficient encapsidation that contained a
      critical region II sequence. Furthermore, we analyzed variants of DHBV that were
      substituted with HHBV sequence over region II and found that the chimeras were
      not fully functional for RNA encapsidation. These results indicate that sequences
      within region II may need to be compatible with other viral components in order
      to function in pgRNA encapsidation.

PMID- 12186893
TI  - Effect of altering the tRNA(Lys)(3) concentration in human immunodeficiency virus
      type 1 upon its annealing to viral RNA, GagPol incorporation, and viral
      infectivity.
AB  - Human immunodeficiency virus type 1 (HIV-1) uses tRNA(Lys)(3) as a primer for
      reverse transcription and, during viral assembly, this tRNA is selectively
      packaged into the virus along with the other major tRNA(Lys), tRNA(Lys)(3).
      Increasing the cytoplasmic concentration of tRNA(Lys)(3) through transfection of
      cells with a plasmid containing both HIV-1 proviral DNA and a tRNA(Lys)(3) gene
      results in a greater incorporation of tRNA(Lys)(3) into virions, which is
      accompanied by increased annealing of tRNA(Lys)(3) to the viral genome and
      increased infectivity of the viral population. Increased viral tRNA(Lys)(3) is
      accompanied by decreased viral tRNA(Lys)(3), with the total tRNA(Lys)/virion and
      the GagPol/Gag ratios remaining unchanged. Viral tRNA(Lys) can be doubled, with
      increases in both tRNA(Lys)(3) and tRNA(Lys)(1,2) concentrations, by
      overexpressing lysyl tRNA synthetase. This also results in increased tRNA(Lys)(3)
      annealing to the viral RNA and increased viral infectivity but, again, no change
      in the GagPol/Gag ratio was observed. This result indicates that GagPol, whose
      interaction is required during packaging, is not a limiting factor during
      tRNA(Lys) incorporation into HIV-1, whereas LysRS is.

PMID- 12186894
TI  - Modalities of interleukin-7-induced human immunodeficiency virus permissiveness
      in quiescent T lymphocytes.
AB  - The metabolic and cell cycle status of primary T lymphocytes conditions their
      susceptibility to human immunodeficiency virus (HIV) and HIV-derived vectors.
      While in fully quiescent T lymphocytes the reverse transcription and nuclear
      import of these retroelements are impaired, leading to an abortive infection,
      various stimuli can induce a state of virus permissiveness. Here, we studied the
      modalities by which interleukin-7 (IL-7), an important controller of T-cell
      homeostasis, exerts this effect. IL-7-exposed cord blood T lymphocytes
      proliferated and were efficiently transduced by HIV-derived vectors. In contrast,
      similarly treated adult peripheral blood (PB) T lymphocytes failed to divide, and
      only a subset of these cells became infectible. HIV-resistant and -sensitive
      subsets of IL-7-treated PB T lymphocytes differed in cell cycle status but not in
      naive, memory, or activation phenotypes. Nuclear factor of activated T cells was
      not induced by IL-7, and cyclosporine did not prevent HIV-mediated gene transfer.
      Furthermore, the phosphatidylinositol 3-kinase (PI3K) inhibitor wortmannin
      blocked IL-7-induced cell survival and Bcl-2 synthesis but had no effect on the
      acquisition of HIV susceptibility, suggesting that IL-7-induced HIV type 1
      permissiveness is not mediated by the PI-3 K pathway and that, perhaps, the
      Jak/STAT5 pathway, the other known mediator of IL-7-triggered signaling in T
      cells, governs this process.

PMID- 12186895
TI  - Intravirion processing of the human immunodeficiency virus type 1 Vif protein by
      the viral protease may be correlated with Vif function.
AB  - The human immunodeficiency virus type 1 (HIV-1) Vif protein is specifically
      packaged into virus particles through an interaction with viral genomic RNA in
      which it associates with the viral nucleoprotein complex. We now demonstrate for
      the first time that virus-associated Vif is subject to proteolytic processing by
      the viral protease (Pr). Pr-dependent processing of Vif was observed both in vivo
      and in vitro. In vivo processing of Vif was cell type independent and evident by
      the appearance of a 7-kDa processing product, which was restricted to cell-free
      virus preparations. Processing of Vif required an active viral Pr and was
      sensitive to Pr inhibitors such as ritonavir. The processing site in Vif was
      characterized both in vivo and in vitro and mapped to Ala(150). Interestingly,
      the Vif processing site is located in a domain that is highly conserved among HIV
      1, HIV-2, and simian immunodeficiency virus Vif isolates. Mutations at or near
      the processing site did not affect protein stability or packaging efficiency but
      had dramatic effects on Vif processing. In general, mutations that markedly
      increased or decreased the sensitivity of Vif to proteolytic processing severely
      impaired or completely abolished Vif function. In contrast, mutations at the same
      site that had little or no effect on processing efficiency also did not influence
      Vif function. None of the mutants affected the ability of the virus to replicate
      in permissive cell lines. Our data suggest that mutations in Vif that cause a
      profound change in the sensitivity to Pr-dependent processing also severely
      impaired Vif function, suggesting that intravirion processing of Vif is important
      for the production of infectious viruses.

PMID- 12186896
TI  - Genetic diversity within human erythroviruses: identification of three genotypes.
AB  - B19 virus is a human virus belonging to the genus Erythrovirus: The genetic
      diversity among B19 virus isolates has been reported to be very low, with less
      than 2% nucleotide divergence in the whole genome sequence. We have previously
      reported the isolation of a human erythrovirus isolate, termed V9, whose sequence
      was markedly distinct (>11% nucleotide divergence) from that of B19 virus. To
      date, the V9 isolate remains the unique representative of a new variant in the
      genus Erythrovirus, and its taxonomic position is unclear. We report here the
      isolation of 11 V9-related viruses. A prospective study conducted in France
      between 1999 and 2001 indicates that V9-related viruses actually circulate at a
      significant frequency (11.4%) along with B19 viruses. Analysis of the nearly full
      length genome sequence of one V9-related isolate (D91.1) indicates that the D91.1
      sequence clusters together with but is notably distant from the V9 sequence (5.3%
      divergence) and is distantly related to B19 virus sequences (13.8 to 14.2%
      divergence). Additional phylogenetic analysis of partial sequences from the V9
      related isolates combined with erythrovirus sequences available in GenBank
      indicates that the erythrovirus group is more diverse than thought previously and
      can be divided into three well-individualized genotypes, with B19 viruses
      corresponding to genotype 1 and V9-related viruses being distributed into
      genotypes 2 and 3.

PMID- 12186897
TI  - Quantitative expression and virus transmission analysis of DC-SIGN on monocyte
      derived dendritic cells.
AB  - The C-type lectins DC-SIGN and DC-SIGNR efficiently bind human immunodeficiency
      virus (HIV) and simian immunodeficiency virus (SIV) strains and can transmit
      bound virus to adjacent CD4-positive cells. DC-SIGN also binds efficiently to the
      Ebola virus glycoprotein, enhancing Ebola virus infection. DC-SIGN is thought to
      be responsible for the ability of dendritic cells (DCs) to capture HIV and
      transmit it to T cells, thus promoting HIV dissemination in vitro and perhaps in
      vivo as well. To investigate DC-SIGN function and expression levels on DCs, we
      characterized a panel of monoclonal antibodies (MAbs) directed against the
      carbohydrate recognition domain of DC-SIGN. Using quantitative fluorescence
      activated cell sorter technology, we found that DC-SIGN is highly expressed on
      immature monocyte-derived DCs, with at least 100,000 copies and often in excess
      of 250,000 copies per DC. There was modest variation (three- to fourfold) in DC
      SIGN expression levels between individuals and between DCs isolated from the same
      individual at different times. Several MAbs efficiently blocked virus binding to
      cell lines expressing human or rhesus DC-SIGN, preventing HIV and SIV
      transmission. Interactions with Ebola virus pseudotypes were also blocked
      efficiently. Despite their ability to block virus-DC-SIGN interactions on cell
      lines, these antibodies only inhibited transmission of virus from DCs by
      approximately 50% or less. These results indicate that factors other than DC-SIGN
      may play important roles in the ability of DCs to capture and transmit HIV.

PMID- 12186898
TI  - Nucleoside analog resistance caused by insertions in the fingers of human
      immunodeficiency virus type 1 reverse transcriptase involves ATP-mediated
      excision.
AB  - Although anti-human immunodeficiency virus type 1 (HIV-1) therapy has prolonged
      the lives of patients, drug resistance is a significant problem. Of particular
      concern are mutations that cause cross-resistance to a particular class of drugs.
      Among the mutations that cause resistance to several nucleoside analogs are the
      insertion of amino acids in the fingers subdomain of HIV-1 reverse transcriptase
      (RT) at positions 69 and 70. These insertions are usually associated with changes
      in the flanking amino acids and with a change to F or Y at position 215. We have
      proposed that the T215F/Y mutation makes the binding of ATP to HIV-1 RT more
      effective, which increases the excision of 3-azido-3'-deoxythymidine-5'
      monophosphate (AZTMP) in vitro and increases zidovudine (AZT) resistance in vivo.
      Although the mechanism of AZT resistance involves enhanced excision, resistance
      to 3TC involves a block to incorporation of the analog. We measured the effects
      of fingers insertion mutations on the misincorporation and excision of several
      nucleoside analogs. RT variants with the amino acid insertions in the fingers and
      T215Y have a decreased level of misincorporation of ddATP and 3TCTP. These
      mutants also have the ability to excise AZTMP by ATP-dependent
      pyrophosphorylysis. However, unlike the classic AZT resistance mutations
      (M41L/D67N/K70R/T215Y or F/K219E or Q), the combination of the amino acid
      insertions in the fingers and the T215Y mutation allows efficient excision of
      ddTMP and d4TMP, even when relatively high levels of deoxynucleoside
      triphosphates are present in the reaction. Although the dideoxynucleoside analogs
      of other nucleosides were excised more slowly than AZTMP, ddTMP, and d4TMP, the
      mutants with the fingers insertion and T215Y excised all of the nucleoside
      analogs that were tested more efficiently than wild-type RT or a mutant RT
      carrying the classical AZT resistance mutations. In the ternary complex
      (RT/template-primer/dNTP), the presence of the bound dNTP prevents the end of the
      primer from gaining access to the nucleotide binding site (N site) where excision
      occurs. Gel shift analysis showed that the amino acid insertions in the fingers
      destabilized the ternary complex compared to wild-type HIV-1 RT. If the ternary
      complex is unstable, the end of the primer can gain access to the N site and
      excision can occur. This could explain the enhanced excision of the nucleoside
      analogs.

PMID- 12186899
TI  - Blockade of human immunodeficiency virus type 1 expression by caveolin-1.
AB  - Caveolin-1 (Cav-1) is a major protein constituent of caveolae, a type of plasma
      membrane raft. We observed that coexpression of human Cav-1 with human
      immunodeficiency virus type 1 (HIV-1) blocked virion production from cells that
      are ordinarily highly permissive. Further investigation showed that this effect
      is specific, occurs at low ratios of Cav-1 to HIV-1 DNA, depends on expression of
      Cav-1 protein, and involves severely impaired expression of HIV-1 proteins. Cav-1
      also blocked HIV-2 expression. In contrast, Cav-1 did not inhibit protein
      expression by a paramyxovirus and did not induce apoptosis or affect cellular
      morphology, cell viability, or cell cycle progression. Although only small
      amounts of HIV-1 virions were released from Cav-1-transfected cells, these were
      fully infectious. Deletion mutagenesis showed that the C-terminal 78 residues
      were as active as the full-length (178-amino-acid) protein in producing the
      block. In contrast, the 100 most N-terminal amino acids of Cav-1, which include
      the previously identified oligomerization and scaffolding domains, were shown to
      be dispensable. Study of single-amino-acid-exchange mutants of Cav-1 established
      that palmitoylation was not required. Additional deletion mutants then identified
      the hydrophobic, membrane-associated domain (residues 101 to 135) as the main
      determinant. Cellular distribution of wild-type and mutant proteins correlated
      with ability to block HIV-1 expression. Finally, Cav-2 also blocked HIV-1
      expression. These data show that coexpression of caveolins can markedly inhibit
      expression of HIV proviral DNA and establish that the inhibition is mediated by
      the hydrophobic, membrane-associated domain.

PMID- 12186900
TI  - Persisting murine cytomegalovirus can reactivate and has unique transcriptional
      activity in ocular tissue.
AB  - Cytomegalovirus (CMV) retinitis is an important ocular complication in human
      immunodeficiency virus-infected individuals and the leading cause of blindness in
      those not undergoing highly active antiretroviral therapy. Murine CMV (MCMV)
      infection of mice has been shown to be a useful small-animal model for the study
      of CMV pathogenesis in the eye. The purpose of this study was to evaluate CMV
      persistence in ocular tissue and to determine the potential for reactivation.
      Following subretinal inoculation of immunocompetent BALB/c mice, tissues were
      tested for infectious virus by plaque assay and for the presence of viral DNA and
      RNA by PCR. The latent phase of the infection in mouse tissues was analyzed by
      plaque assay, PCR, and explantation cocultivation in both immunocompetent and
      cyclophosphamide-treated mice. The acute phase of the infection was resolved by 2
      to 3 weeks postinfection, while viral DNA persisted beyond 12 months. Immediate
      early 1 transcripts were detected in 100% of the ocular samples tested, and
      glycoprotein H transcripts were detected in 86% of the samples, but no difference
      in viral DNA or RNA levels between immunocompetent and immunosuppressed animals
      was measured. Irrespective of immune status, no in vivo reactivation was
      detected; however, reactivated virus was observed in 76 to 82% of the eyes
      following explantation onto a permissive cell layer. The transcriptional activity
      and relatively high frequency of explantation-induced reactivation in both
      immunocompetent and immunosuppressed mice suggest that control of MCMV latency in
      ocular tissue might involve other regulatory events that are not entirely
      dependent on intact specific immunity.

PMID- 12186901
TI  - Induction of immune responses in mice and monkeys to Ebola virus after
      immunization with liposome-encapsulated irradiated Ebola virus: protection in
      mice requires CD4(+) T cells.
AB  - Ebola Zaire virus (EBO-Z) causes severe hemorrhagic fever in humans, with a high
      mortality rate. It is thought that a vaccine against EBO-Z may have to induce
      both humoral and cell-mediated immune responses to successfully confer
      protection. Because it is known that liposome-encapsulated antigens induce both
      antibody and cellular responses, we evaluated the protective efficacy of liposome
      encapsulated irradiated EBO-Z [L(EV)], which contains all of the native EBO-Z
      proteins. In a series of experiments, mice immunized intravenously with L(EV)
      were completely protected (94/94 mice) against illness and death when they were
      challenged with a uniformly lethal mouse-adapted variant of EBO-Z. In contrast,
      only 55% of mice immunized intravenously with nonencapsulated irradiated virus
      (EV) survived challenge, and all became ill. Treatment with anti-CD4 antibodies
      before or during immunization with L(EV) eliminated protection, while treatment
      with anti-CD8 antibodies had no effect, thus indicating a requirement for CD4(+)
      T lymphocytes for successful immunization. On the other hand, treatment with
      either anti-CD4 or anti-CD8 antibodies after immunization did not abolish the
      protection. After immunization with L(EV), antigen-specific gamma interferon (IFN
      gamma)-secreting CD4(+) T lymphocytes were induced as analyzed by enzyme-linked
      immunospot assay. Anti-CD4 monoclonal antibody treatment abolished IFN gamma
      production (80 to 90% inhibition compared to that for untreated mice). Mice
      immunized with L(EV), but not EV, developed cytotoxic T lymphocytes specific to
      two peptides (amino acids [aa] 161 to 169 and aa 231 to 239) present in the amino
      terminal end of the EBO-Z surface glycoprotein. Because of the highly successful
      results in the mouse model, L(EV) was also tested in three cynomolgus monkeys.
      Although immunization of the monkeys with L(EV)-induced virus-neutralizing
      antibodies against EBO-Z caused a slight delay in the onset of illness, it did
      not prevent death.

PMID- 12186902
TI  - In vivo association of adenovirus large E1A protein with the human mediator
      complex in adenovirus-infected and -transformed cells.
AB  - The adenovirus large E1A protein activates transcription from early viral
      promoters by a mechanism that requires a forty amino acid zinc finger activation
      domain in E1A conserved region 3 (CR3). Recent results indicate that activation
      by a Gal4 DNA-binding domain-E1A-CR3 fusion requires an interaction between the
      E1A-CR3 zinc finger and the Sur2 subunit of the mammalian Mediator (of
      transcription) complex. Although several host proteins have been shown to bind
      stably to E1A proteins in adenovirus-infected and -transformed cells, an in vivo
      interaction with Mediator complex subunits has not been described previously.
      Using immunoprecipitation and gel filtration analyses of nuclear extracts
      prepared from HeLa cells infected with adenovirus 5 or mutants that express
      either large or small E1A specifically and from adenovirus 5-transformed cells,
      we report here that large E1A, but not small E1A, binds to Mediator complex in
      vivo. Only approximately 1 to 10% of large E1A is bound to Mediator complex at 18
      h postinfection and in transformed cells, probably explaining why Mediator
      complex subunits were not identified among cellular E1A-binding proteins
      described earlier. Surprisingly, even though extracted Mediator can
      quantitatively bind to an E1A-CR3 affinity column, only on the order of 1% of
      cellular Mediator complex is bound by E1A in vivo. Much of the large E1A bound to
      Mediator in 293 cells is in a stable complex that includes RNA polymerase II,
      leading us to suggest that the interaction of E1A-CR3 with Mediator stabilizes
      the interaction of Mediator with the polymerase. This stabilization of the
      interaction between Mediator and RNA polymerase II may contribute to the
      mechanism of activation by E1A-CR3.

PMID- 12186904
TI  - Subversion of cell signaling pathways by hepatitis C virus nonstructural 5A
      protein via interaction with Grb2 and P85 phosphatidylinositol 3-kinase.
AB  - Hepatitis C virus (HCV) sets up a persistent infection in patients that likely
      involves a complex virus-host interaction. We previously found that the HCV
      nonstructural 5A (NS5A) protein interacts with growth factor receptor-binding
      protein 2 (Grb2) adaptor protein and inhibits the activation of extracellular
      signal-regulated kinases 1 and 2 (ERK1/2) by epidermal growth factor (EGF). In
      the present study, we extended this analysis and investigated the specificity of
      the Grb2-NS5A interaction and whether the subversion of mitogenic signaling
      involves additional pathways. NS5A containing mutations within the C-terminal
      proline-rich motif neither bound Grb2 nor inhibited ERK1/2 activation by EGF,
      demonstrating that NS5A-Grb2 binding and downstream effects were due to direct
      interactions. Interestingly, NS5A could also form a complex with the Grb2
      associated binder 1 (Gab1) protein in an EGF treatment-dependent manner. However,
      the NS5A-Gab1 association, which appeared indirect, was not mediated by direct
      NS5A-Grb2 interaction but was likely dependent on direct NS5A interaction with
      the p85 subunit of phosphatidylinositol 3-kinase (PI3K). The in vivo association
      of NS5A with p85 PI3K required the N-terminal, but not the C-terminal, region of
      NS5A. The downstream effects of the NS5A-p85 PI3K interaction included increased
      tyrosine phosphorylation of p85 PI3K in response to EGF. Consistent with this
      observation and the antiapoptotic properties of NS5A, we also detected enhanced
      tyrosine phosphorylation of the downstream AKT protein kinase and increased
      serine phosphorylation of BAD, a proapoptotic factor and an AKT substrate, in the
      presence of NS5A. These results collectively suggest a model in which NS5A
      interacts with Grb2 to inhibit mitogenic signaling while simultaneously promoting
      the PI3K-AKT cell survival pathway by interaction with p85 PI3K, which may
      represent a crucial step in HCV persistence and pathogenesis.

PMID- 12186905
TI  - Cleavage at the furin consensus sequence RAR/KR(109) and presence of the
      intervening peptide of the respiratory syncytial virus fusion protein are
      dispensable for virus replication in cell culture.
AB  - Proteolytic processing of the respiratory syncytial virus F (fusion) protein
      results in the generation of the disulfide-linked subunits F1 and F2 and in the
      release of pep27, a glycopeptide originally located between the two furin
      cleavage sites FCS-1 (RKRR(136)) and FCS-2 (RAR/KR(109)). We made use of reverse
      genetics to study the importance of FCS-2 and of pep27 for BRSV replication in
      cell culture. Replacement of FCS-2 in the F protein of recombinant viruses by
      either of the sequences NANR(109), RANN(109) or SANN(109), respectively,
      abolished proteolytic processing at this position, whereas the cleavage of FCS-1
      was not affected. All mutants replicated in calf kidney and Vero cells in the
      absence of exogenous trypsin, although somewhat higher titers of BRSV containing
      the NANR(109) or the RANN(109) motif were achieved in the presence of trypsin.
      The virus mutants showed a reduced cytopathic effect which was lowest in the case
      of the SANN(109) mutant. These findings demonstrate that cleavage at FCS-2 is
      dispensable for replication of respiratory syncytial virus in cell culture. A
      deletion mutant containing FCS-1 but lacking FCS-2 and most of pep27 replicated
      in cell culture as efficiently as the parental virus, indicating that this domain
      of the F protein is not essential for virus maturation and infectivity.

PMID- 12186903
TI  - Analysis of the adenovirus E1B-55K-anchored proteome reveals its link to
      ubiquitination machinery.
AB  - During the early phase of infection, the E1B-55K protein of adenovirus type 5
      (Ad5) counters the E1A-induced stabilization of p53, whereas in the late phase,
      E1B-55K modulates the preferential nucleocytoplasmic transport and translation of
      the late viral mRNAs. The mechanism(s) by which E1B-55K performs these functions
      has not yet been clearly elucidated. In this study, we have taken a proteomics
      based approach to identify and characterize novel E1B-55K-associated proteins. A
      multiprotein E1B-55K-containing complex was immunopurified from Ad5-infected HeLa
      cells and found to contain E4-orf6, as well as several cellular factors
      previously implicated in the ubiquitin-proteasome-mediated destruction of
      proteins, including Cullin-5, Rbx1/ROC1/Hrt1, and Elongins B and C. We further
      demonstrate that a complex containing these as well as other proteins is capable
      of directing the polyubiquitination of p53 in vitro. These ubiquitin ligase
      components were found in a high-molecular-mass complex of 800 to 900 kDa. We
      propose that these newly identified binding partners (Cullin-5, Elongins B and C,
      and Rbx1) complex with E1B-55K and E4-orf6 during Ad infection to form part of an
      E3 ubiquitin ligase that targets specific protein substrates for degradation. We
      further suggest that E1B-55K functions as the principal substrate recognition
      component of this SCF-type ubiquitin ligase, whereas E4-orf6 may serve to
      nucleate the assembly of the complex. Lastly, we describe the identification and
      characterization of two novel E1B-55K interacting factors, importin-alpha 1 and
      pp32, that may also participate in the functions previously ascribed to E1B-55K
      and E4-orf6.

PMID- 12186906
TI  - Potent and specific inhibition of human immunodeficiency virus type 1 replication
      by RNA interference.
AB  - Synthetic small interfering RNAs (siRNAs) have been shown to induce the
      degradation of specific mRNA targets in human cells by inducing RNA interference
      (RNAi). Here, we demonstrate that siRNA duplexes targeted against the essential
      Tat and Rev regulatory proteins encoded by human immunodeficiency virus type 1
      (HIV-1) can specifically block Tat and Rev expression and function. More
      importantly, we show that these same siRNAs can effectively inhibit HIV-1 gene
      expression and replication in cell cultures, including those of human T-cell
      lines and primary lymphocytes. These observations demonstrate that RNAi can
      effectively block virus replication in human cells and raise the possibility that
      RNAi could provide an important innate protective response, particularly against
      viruses that express double-stranded RNAs as part of their replication cycle.

PMID- 12186908
TI  - Upregulation of surface feline CXCR4 expression following ectopic expression of
      CCR5: implications for studies of the cell tropism of feline immunodeficiency
      virus.
AB  - Feline CXCR4 and CCR5 were expressed in feline cells as fusion proteins with
      enhanced green fluorescent protein (EGFP). Expression of the EGFP fusion proteins
      was localized to the cell membrane, and surface expression of CXCR4 was confirmed
      by using a cross-species-reactive anti-CXCR4 monoclonal antibody. Ectopic
      expression of feline CCR5 enhanced expression of either endogenous feline CXCR4
      or exogenous feline or human CXCR4 expressed from a retrovirus vector, indicating
      that experiments investigating the effect of CCR5 expression on feline
      immunodeficiency virus (FIV) infection must be interpreted with caution.
      Susceptibility to infection with cell culture-adapted strains of FIV or to
      syncytium formation following transfection with a eukaryotic vector expressing an
      env gene from a cell culture-adapted strain of virus correlated with expression
      of either human or feline CXCR4, whereas feline CCR5 had no effect. In contrast,
      neither CXCR4 nor CCR5 rendered cells permissive to either productive infection
      with primary strains of FIV or syncytium formation following transfection with
      primary env gene expression vectors. Screening a panel of Ghost cell lines
      expressing diverse human chemokine receptors confirmed that CXCR4 alone supported
      fusion mediated by the FIV Env from cell culture-adapted viruses. CXCR4
      expression was upregulated in Ghost cells coexpressing CXCR4 and CCR5 or CXCR4,
      CCR5, and CCR3, and susceptibility to FIV infection could be correlated with the
      level of CXCR4 expression. The data suggest that beta-chemokine receptors may
      influence FIV infection by modulating the expression of CXCR4.

PMID- 12186907
TI  - Herpes simplex virus type 1 evades the effects of antibody and complement in
      vivo.
AB  - Herpes simplex virus type 1 (HSV-1) encodes a complement-interacting
      glycoprotein, gC, and an immunoglobulin G (IgG) Fc binding glycoprotein, gE, that
      mediate immune evasion by affecting multiple aspects of innate and acquired
      immunity, including interfering with complement components C1q, C3, C5, and
      properdin and blocking antibody-dependent cellular cytotoxicity. Previous studies
      evaluated the individual contributions of gC and gE to immune evasion.
      Experiments in a murine model that examines the combined effects of gC and gE
      immune evasion on pathogenesis are now reported. Virulence of wild-type HSV-1 is
      compared with mutant viruses defective in gC-mediated C3 binding, gE-mediated IgG
      Fc binding, or both immune evasion activities. Eliminating both activities
      greatly increased susceptibility of HSV-1 to antibody and complement
      neutralization in vitro and markedly reduced virulence in vivo as measured by
      disease scores, virus titers, and mortality. Studies with C3 knockout mice
      indicated that other activities attributed to these glycoproteins, such as gC
      mediated virus attachment to heparan sulfate or gE-mediated cell-to-cell spread,
      do not account for the reduced virulence of mutant viruses. The results support
      the importance of gC and gE immune evasion in vivo and suggest potential new
      targets for prevention and treatment of HSV disease.

PMID- 12186909
TI  - Combination of drugs and drug-resistant reverse transcriptase results in a
      multiplicative increase of human immunodeficiency virus type 1 mutant
      frequencies.
AB  - Replication of drug-resistant human immunodeficiency virus type 1 (HIV-1) in the
      presence of drug can lead to the failure of antiretroviral drug treatment. Drug
      failure is associated with the accumulation of drug resistance mutations.
      Previous studies have shown that 3'-azido-3'-deoxythymidine (AZT), (-)2',3'
      dideoxy-3'-thiacytidine (3TC), and AZT-resistant HIV-1 reverse transcriptase (RT)
      can increase the virus in vivo mutation rate. In this study, the combined effects
      of drug-resistant RT and antiretroviral drugs on the HIV-1 mutant frequency were
      determined. In most cases, a multiplicative effect was observed with AZT
      resistant or AZT/3TC dually resistant RT and several drugs (i.e., AZT, 3TC,
      hydroxyurea, and thymidine) and led to increases in the odds of recovering virus
      mutants to over 20 times that of the HIV-1 mutant frequency in the absence of
      drug or drug-resistance mutations. This observation indicates that HIV-1 can
      mutate at a significantly higher rate when drug-resistant virus replicates in the
      presence of drug. These increased mutant frequencies could have important
      implications for HIV-1 population dynamics and drug therapy regimens.

PMID- 12186910
TI  - Complete genome sequence and analyses of the subgenomic RNAs of sweet potato
      chlorotic stunt virus reveal several new features for the genus Crinivirus.
AB  - The complete nucleotide sequences of genomic RNA1 (9,407 nucleotides [nt]) and
      RNA2 (8,223 nt) of Sweet potato chlorotic stunt virus (SPCSV; genus Crinivirus,
      family Closteroviridae) were determined, revealing that SPCSV possesses the
      second largest identified positive-strand single-stranded RNA genome among plant
      viruses after Citrus tristeza virus. RNA1 contains two overlapping open reading
      frames (ORFs) that encode the replication module, consisting of the putative
      papain-like cysteine proteinase, methyltransferase, helicase, and polymerase
      domains. RNA2 contains the Closteroviridae hallmark gene array represented by a
      heat shock protein homologue (Hsp70h), a protein of 50 to 60 kDa depending on the
      virus, the major coat protein, and a divergent copy of the coat protein. This
      grouping resembles the genome organization of Lettuce infectious yellows virus
      (LIYV), the only other crinivirus for which the whole genomic sequence is
      available. However, in striking contrast to LIYV, the two genomic RNAs of SPCSV
      contained nearly identical 208-nt-long 3' terminal sequences, and the ORF for a
      putative small hydrophobic protein present in LIYV RNA2 was found at a novel
      position in SPCSV RNA1. Furthermore, unlike any other plant or animal virus,
      SPCSV carried an ORF for a putative RNase III-like protein (ORF2 on RNA1).
      Several subgenomic RNAs (sgRNAs) were detected in SPCSV-infected plants,
      indicating that the sgRNAs formed from RNA1 accumulated earlier in infection than
      those of RNA2. The 5' ends of seven sgRNAs were cloned and sequenced by an
      approach that provided compelling evidence that the sgRNAs are capped in infected
      plants, a novel finding for members of the Closteroviridae.

PMID- 12186911
TI  - Truncation of herpes simplex virus type 2 glycoprotein B increases its cell
      surface expression and activity in cell-cell fusion, but these properties are
      unrelated.
AB  - Formation of small polykaryons by cell-cell fusion is characteristic of herpes
      simplex virus (HSV) lesions, but the great majority of viruses isolated from such
      lesions produce only limited cell fusion in tissue culture. Because of this, HSV
      laboratory strains that produce extensive cell fusion (syncytium formation) in
      culture are regarded as variants or mutants. Furthermore, the rarity of clinical
      isolates able to produce syncytia in culture suggests that extensive cell fusion
      is deleterious in vivo. Mutations that confer a syncytial phenotype can then be
      regarded as bypassing a mechanism that normally limits cell fusion. Determination
      of how these mutations, some of which are in the cytoplasmic tail of glycoprotein
      B (gB), lead to syncytium formation will likely reveal how fusion is controlled.
      Here we show the following. (i) Truncation of the cytoplasmic tail of HSV type 2
      gB (gB-2) by a minimum of 25 residues or a maximum of 49 residues produces a
      syncytial phenotype. (ii) Truncation by 20 to 49 residues increases cell fusion
      when gB-2 is coexpressed with only gD-2, gH-2, and gL-2. (iii) Truncation by 25
      or more residues removes a potential endocytosis motif and increases gB-2 cell
      surface expression. (iv) Mutation of this motif increases gB-2 cell surface
      expression but does not increase fusogenic activity, whereas mutation of another
      potential endocytosis motif does not increase surface expression but does
      increase fusogenic activity. Therefore, syncytial mutations in the cytoplasmic
      tail of gB-2 do not act by increasing cell surface levels of the protein.

PMID- 12186912
TI  - Roles for the cytoplasmic tails of the fusion and hemagglutinin-neuraminidase
      proteins in budding of the paramyxovirus simian virus 5.
AB  - The efficient release of many enveloped viruses from cells involves the
      coalescence of viral components at sites of budding on the plasma membrane of
      infected cells. This coalescence is believed to require interactions between the
      cytoplasmic tails of surface glycoproteins and the matrix (M) protein. For the
      paramyxovirus simian virus 5 (SV5), the cytoplasmic tail of the hemagglutinin
      neuraminidase (HN) protein has been shown previously to be important for normal
      virus budding. To investigate a role for the cytoplasmic tail of the fusion (F)
      protein in virus assembly and budding, we generated a series of F cytoplasmic
      tail-truncated recombinant viruses. Analysis of these viruses in tissue culture
      indicated that the cytoplasmic tail of the F protein was dispensable for normal
      virus replication and budding. To investigate further the requirements for
      assembly and budding of SV5, we generated two double-mutant recombinant viruses
      that lack 8 amino acids of the predicted 17-amino-acid HN protein cytoplasmic
      tail in combination with truncation of either 10 or 18 amino acids from the
      predicted 20-amino-acid F protein cytoplasmic tail. Both of the double mutant
      recombinant viruses displayed a replication defect in tissue culture and a
      budding defect, the extent of which was dependent on the length of the remaining
      F cytoplasmic tail. Taken together, this work and our earlier data on virus-like
      particle formation (A. P. Schmitt, G. P. Leser, D. L. Waning, and R. A. Lamb, J.
      Virol. 76:3953-3964, 2002) suggest a redundant role for the cytoplasmic tails of
      the HN and F proteins in virus assembly and budding.

PMID- 12186913
TI  - Release of macrophage migration inhibitory factor and CXCL8/interleukin-8 from
      lung epithelial cells rendered necrotic by influenza A virus infection.
AB  - Bronchiolar epithelial cells are the prime targets for influenza A virus
      infection. It still remains to be clarified which signals are generated from
      these cells to initiate an immune response. Among chemokines, viral infection of
      primary lung epithelial cells triggered exclusively the release of
      CXCL8/interleukin-8 (IL-8), which contrasts with our previous observation that
      influenza A virus induced in monocytes the expression of mononuclear-leukocyte
      attracting chemokines and even suppressed the production of neutrophil-attracting
      chemokines. Therefore, we speculated that it may be advantageous for respiratory
      epithelial cells to release primarily neutrophil-attracting CXCL8/IL-8 since
      neutrophils rapidly remove necrotic debris and are the first line of defense
      against bacterial superinfections. This concept has also been supported by our
      finding that influenza A virus infection led to necrosis of lung epithelial
      cells. This is in striking contrast to previous studies where influenza A virus
      infection induced apoptosis in monocytes and epithelial cells from origins other
      than the lung. Thus, the cell type instead of the virus determines which death
      pathway will be followed. In addition to the release of CXCL8/IL-8, we obtained a
      massive release of macrophage migration inhibitory factor (MIF) from virus
      infected lung cells. However, whereas the CXCL8/IL-8 secretion was accompanied by
      induced gene activation, the transcription rate of MIF remained unchanged during
      the infection course and the virus-induced MIF release was predominantly a
      discharge from intracellular stores, suggesting that MIF is passively released
      upon cell death. Despite virus induced necrosis, the passively liberated MIF
      remained bioactive. Considering the well-established immunostimulatory effects of
      MIF on different leukocyte subsets, is its very likely that enhanced levels of
      MIF may contribute to the host immune response during the acute phase of
      influenza A virus infection in humans.

PMID- 12186914
TI  - A novel cell entry pathway for a DAF-using human enterovirus is dependent on
      lipid rafts.
AB  - The glycosylphosphatidylinositol (GPI)-anchored complement regulatory protein
      decay-accelerating factor (DAF) is used by a number of enteroviruses as a
      receptor during infection. DAF and other GPI-anchored proteins can be found in
      cholesterol-rich ordered domains within the plasma membrane that are known as
      "lipid rafts." We have shown, by using drugs to specifically inhibit various
      endocytosis routes, that infection by a DAF-using strain of echovirus 11 (EV11)
      is dependent upon cholesterol and an intact cytoskeleton, whereas a non-DAF-using
      mutant derived from it was unaffected by these drugs. Using RNA transfection and
      virus-binding assays, we have shown that this requirement for cholesterol, the
      actin cytoskeleton, and the microtubule network occurs postbinding of the virus
      but prior to uncoating of the RNA, indicating a role during virus entry. Confocal
      microscopy of virus infection supported the role of cholesterol and the
      cytoskeleton during entry. In addition, [(35)S]methionine-labeled DAF-using EV11,
      but not the non-DAF-using EV11, could be copurified with lipid raft components
      during infection after Triton X-100 extraction. These data indicate that DAF
      usage by EV11 enables the virus to associate with lipid rafts and enter cells
      through this novel route.

PMID- 12186915
TI  - Genetic requirements for homologous recombination in Autographa californica
      nucleopolyhedrovirus.
AB  - It is known that baculovirus infection promotes high-frequency recombination
      between its genomes and plasmid DNA during the construction of recombinant
      viruses for foreign gene expression. However, little is known about the viral
      genes necessary to promote homologous recombination (HR). We developed an assay
      to identify viral genes that are necessary to stimulate HR. In this assay, we
      used two plasmids containing extensive sequence homology that yielded a visible
      and quantifiable phenotype if HR occurred. The plasmids contained the green
      fluorescent protein gene (gfp) that was mutated at either the N or the C terminus
      and a viral origin of DNA replication. When the plasmids containing these mutant
      gfp genes were transfected into insect cells alone or together, few green
      fluorescent protein (GFP)-positive cells were observed, confirming that the host
      cell machinery alone was not able to promote high levels of HR. However, if viral
      DNA or viral genes involved in DNA replication were cotransfected into cells
      along with the mutant gfp-containing plasmids, a dramatic increase in GFP
      positive cells was observed. The viral genes ie-1, ie-2, lef-7, and p35 were
      found to be important for efficient HR in the presence of all other DNA
      replication genes. However, ie-1 and ie-2 were sufficient to promote HR in the
      absence of other viral genes. Recombination substrates lacking a viral origin of
      replication had similar genetic requirements for recombination but were less
      dependent on ie-1. Interestingly, even though HR was stimulated by the presence
      of a viral origin of DNA replication, virally stimulated HR could proceed in the
      presence of the DNA synthesis inhibitor aphidicolin.

PMID- 12186916
TI  - Interaction of hepatitis C virus-like particles and cells: a model system for
      studying viral binding and entry.
AB  - Hepatitis C virus-like particles (HCV-LPs) containing the structural proteins of
      HCV H77 strain (1a genotype) was used as a model for HCV virion to study virus
      cell interaction. HCV-LPs showed a buoyant density of 1.17 to 1.22 g/cm(3) in a
      sucrose gradient and formed double-shelled particles 35 to 49 nm in diameter.
      Flow cytometry analysis by an indirect method (detection with anti-E2 antibody)
      and a direct method (use of dye-labeled HCV-LPs) showed that HCV-LPs binds to
      several human hepatic (primary hepatocytes, HepG2, HuH7, and NKNT-3) and T-cell
      (Molt-4) lines. HCV-LPs binding to cells occurred in a dose- and calcium
      dependent manner and was not mediated by CD81. Scatchard plot analysis suggests
      the presence of two binding sites for HCV-LPs with high (K(d) approximately 1
      microg/ml) and low (K(d) approximately 50 to 60 microg/ml) affinities of binding.
      Anti-E1 and -E2 antibodies inhibited HCV-LPs binding to cells. While
      preincubation of HCV-LPs with very-low-density lipoprotein (VLDL), low-density
      lipoprotein (LDL), or high-density lipoprotein (HDL) blocked its binding to
      cells, preincubation of cells with VLDL, LDL, HDL, or anti-LDL-R antibody did
      not. Confocal microscopy analysis showed that, after binding to cells, dye
      labeled HCV-LPs were internalized into the cytoplasm. This process could be
      inhibited with anti-E1 or anti-E2 antibodies, suggesting that E1 and E2 proteins
      mediate HCV-LPs binding and, subsequently, their entry into cells. Altogether,
      our results indicate that HCV-LPs can be used to further characterize the
      mechanisms involved in the early steps of HCV infection.

PMID- 12186917
TI  - Hepatitis C virus core protein leads to immune suppression and liver damage in a
      transgenic murine model.
AB  - Hepatitis C virus (HCV) is remarkably efficient in establishing persistent
      infection, possibly mediated by an impaired immune response to HCV infection.
      There is compelling evidence that HCV can infect immune cells, such as
      macrophages, B cells, and T cells. It has been previously reported that HCV core,
      the first protein expressed during the early phase of viral infection, contains
      the immunomodulatory function of suppressing host immune responses. This altered
      function of immune cells caused by HCV infection may explain the ineffective
      immune response to HCV. To further characterize the immunomodulatory role of HCV
      core in vivo, we generated transgenic (TG) mice by directing the expression of
      core protein to T lymphocytes by using the CD2 promoter. T-lymphocyte responses,
      including the production of gamma interferon and interleukin-2, were
      significantly diminished in these mice compared to their non-TG littermates. The
      inhibition of T-lymphocyte responsiveness may be due to the increased
      susceptibility of peripheral T lymphocytes to Fas-mediated apoptosis.
      Surprisingly, significant lymphocyte infiltration was observed in the portal
      tracts of livers isolated from core TG mice, associated with increasing serum
      alanine aminotransferase levels. Moreover, no intrahepatic lymphocytes or liver
      damage was found in non-TG littermates and core TG mice bred to Fas-deficient lpr
      mice. These results suggest that HCV core drives liver injury by increasing Fas
      mediated apoptosis and liver infiltration of peripheral T cells.

PMID- 12186918
TI  - Overexpression of promyelocytic leukemia protein precludes the dispersal of ND10
      structures and has no effect on accumulation of infectious herpes simplex virus 1
      or its proteins.
AB  - A key early event in the replication of herpes simplex virus 1 (HSV-1) is the
      localization of infected-cell protein no. 0 (ICP0) in nuclear structures knows as
      ND10 or promyelocytic leukemia oncogenic domains (PODs). This is followed by
      dispersal of ND10 constituents such as the promyelocytic leukemia protein (PML),
      CREB-binding protein (CBP), and Daxx. Numerous experiments have shown that this
      dispersal is mediated by ICP0. PML is thought to be the organizing structural
      component of ND10. To determine whether the virus targets PML because it is
      inimical to viral replication, telomerase-immortalized human foreskin fibroblasts
      and HEp-2 cells were transduced with wild-type baculovirus or a baculovirus
      expressing the M(r) 69,000 form of PML. The transduced cultures were examined for
      expression and localization of PML in mock-infected and HSV-1-infected cells. The
      results obtained from studies of cells overexpressing PML were as follows. (i)
      Transduced cells accumulate large amounts of unmodified and SUMO-I-modified PML.
      (ii) Mock-infected cells exhibited enlarged ND10 structures containing CBP and
      Daxx in addition to PML. (iii) In infected cells, ICP0 colocalized with PML in
      ND10 early in infection, but the two proteins did not overlap or were juxtaposed
      in orderly structures. (iv) The enlarged ND10 structures remained intact at least
      until 12 h after infection and retained CBP and Daxx in addition to PML. (v)
      Overexpression of PML had no effect on the accumulation of viral proteins
      representative of alpha, beta, or gamma groups and had no effect on the
      accumulation of infectious virus in cells infected with wild-type virus or a
      mutant (R7910) from which the alpha 0 genes had been deleted. These results
      indicate the following: (i) PML overexpressed in transduced cells cannot be
      differentiated from endogenous PML with respect to sumoylation and localization
      in ND10 structures. (ii) PML does not affect viral replication or the changes in
      the localization of ICP0 through infection. (iii) Disaggregation of ND10
      structures is not an obligatory event essential for viral replication.

PMID- 12186919
TI  - Interaction of the Vp3 nuclear localization signal with the importin alpha 2/beta
      heterodimer directs nuclear entry of infecting simian virus 40.
AB  - For nuclear entry of large nucleoprotein complexes, it is thought that one key
      nuclear localization signal (NLS) of a protein component becomes exposed to
      mediate importin recognition. We show that the nuclear entry of simian virus 40
      involves a dynamic interplay between two distinct interiorly situated capsid
      NLSs, the Vp1 NLS and the Vp3 NLS, and the selective exposure and importin
      recognition of the Vp3 NLS. The Vp3 NLS-null mutants assembled normally into
      virion-like particles (VLP) in mutant DNA-transfected cells. When used to infect
      a new host, the null VLP entered the cell normally but was impaired in viral DNA
      nuclear entry due to a lack of recognition by the importin alpha 2/beta
      heterodimer, leading to reduced viability. Both Vp3 and Vp1 NLSs directed
      importin interaction in vitro, but the Vp1 NLS, which overlaps the Vp1 DNA
      binding domain, did not bind importins in the presence of DNA. The results
      suggest that certain canonical NLSs within a nucleoprotein complex, such as the
      Vp1 NLS, can be masked from functioning by binding to the nucleic acid component
      and that the availability of an NLS that is not masked and can become exposed for
      importin binding, such as the Vp3 NLS, is a general feature of the nuclear entry
      of the nucleoprotein complexes, including those of other animal viruses.

PMID- 12186920
TI  - In vivo gene transfer using a nonprimate lentiviral vector pseudotyped with Ross
      River Virus glycoproteins.
AB  - Vectors derived from lentiviruses provide a promising gene delivery system. We
      examined the in vivo gene transfer efficiency and tissue or cell tropism of a
      feline immunodeficiency virus (FIV)-based lentiviral vector pseudotyped with the
      glycoproteins from Ross River Virus (RRV). RRV glycoproteins were efficiently
      incorporated into FIV virions, generating preparations of FIV vector, which after
      concentration attain titers up to 1.5 x 10(8) TU/ml. After systemic
      administration, RRV-pseudotyped FIV vectors (RRV/FIV) predominantly transduced
      the liver of recipient mice. Transduction efficiency in the liver with the
      RRV/FIV was ca. 20-fold higher than that achieved with the vesicular stomatitis
      virus G protein (VSV-G) pseudotype. Moreover, in comparison to VSV-G, the RRV
      glycoproteins caused less cytotoxicity, as determined from the levels of glutamic
      pyruvic transaminase and glutamic oxalacetic transaminase in serum. Although
      hepatocytes were the main liver cell type transduced, nonhepatocytes (mainly
      Kupffer cells) were also transduced. The percentages of the transduced
      nonhepatocytes were comparable between RRV and VSV-G pseudotypes and did not
      correlate with the production of antibody against the transgene product. After
      injection into brain, RRV/FIV preferentially transduced neuroglial cells
      (astrocytes and oligodendrocytes). In contrast to the VSV-G protein that targets
      predominantly neurons, <10% of the brain cells transduced with the RRV
      pseudotyped vector were neurons. Finally, the gene transfer efficiencies of
      RRV/FIV after direct application to skeletal muscle or airway were also examined
      and, although transgene-expressing cells were detected, their proportions were
      low. Our data support the utility of RRV glycoprotein-pseudotyped FIV lentiviral
      vectors for hepatocyte- and neuroglia-related disease applications.

PMID- 12186921
TI  - 5'-long terminal repeat-selective CpG methylation of latent human T-cell leukemia
      virus type 1 provirus in vitro and in vivo.
AB  - CpG methylation of the human T-cell leukemia virus type 1 (HTLV-1) long terminal
      repeat (LTR) has been implicated in proviral latency, but there is presently
      little information available regarding the pattern of LTR methylation and its
      effect on viral gene expression. To gain insight into the mechanisms of HTLV-1
      latency, we have studied methylation of individual CpG sites in the U3-R region
      of the integrated proviral LTR by using bisulfite genomic sequencing methods.
      Surprisingly, our results reveal selective hypermethylation of the 5' LTR and
      accompanying hypomethylation of the 3' LTR in both latently infected cell lines
      and adult T-cell leukemia (ATL) cells having a complete provirus. Moreover, we
      observed a lack of CpG methylation in the LTRs of 5'-defective proviruses
      recovered from ATL samples, which is consistent with the selective
      hypomethylation of the 3' LTR. Thus, the integrated HTLV-1 provirus in these
      carriers appears to be hypermethylated in the 5' LTR and hypomethylated in the 3'
      LTR. These results, together with the observation that proviral gene expression
      is reactivated by 5-azacytidine in latently infected cell lines, indicate that
      selective hypermethylation of the HTLV-1 5' LTR is common both in vivo and in
      vitro. Thus, hypermethylation of the 5' LTR appears to be an important mechanism
      by which HTLV-1 gene expression is repressed during viral latency.

PMID- 12186922
TI  - The antiviral efficacy of the murine alpha-1 interferon transgene against ocular
      herpes simplex virus type 1 requires the presence of CD4(+), alpha/beta T-cell
      receptor-positive T lymphocytes with the capacity to produce gamma interferon.
AB  - Alpha/beta interferons (IFN-alpha/betas) are known to antagonize herpes simplex
      virus type 1 (HSV-1) infection by directly blocking viral replication and
      promoting additional innate and adaptive, antiviral immune responses. To further
      define the relationship between the adaptive immune response and IFN-alpha/beta,
      the protective effect induced following the topical application of plasmid DNA
      containing the murine IFN-alpha 1 transgene onto the corneas of wild-type and T
      cell-deficient mice was evaluated. Mice homozygous for both the T-cell receptor
      (TCR) beta- and delta-targeted mutations expressing no alpha beta or gamma delta
      TCR (alpha beta/gamma delta TCR double knockout [dKO]) treated with the IFN-alpha
      1 transgene succumbed to ocular HSV-1 infection at a rate similar to that of
      alpha beta/gamma delta TCR dKO mice treated with the plasmid vector DNA.
      Conversely, mice with targeted disruption of the TCR delta chain and expressing
      no gamma delta TCR(+) cells treated with the IFN-alpha 1 transgene survived the
      infection to a greater extent than the plasmid vector-treated counterpart and at
      a level similar to that of wild-type controls treated with the IFN-alpha 1
      transgene. By comparison, mice with targeted disruption of the TCR beta chain and
      expressing no alpha beta TCR(+) cells (alpha beta TCR knockout [KO]) showed no
      difference upon treatment with the IFN-alpha1 transgene or the plasmid vector
      control, with 0% survival following HSV-1 infection. Adoptively transferring
      CD4(+) but not CD8(+) T cells from wild-type but not IFN-gamma-deficient mice
      reestablished the antiviral efficacy of the IFN-alpha 1 transgene in alpha beta
      TCR KO mice. Collectively, the results indicate that the protective effect
      mediated by topical application of a plasmid construct containing the murine IFN
      alpha 1 transgene requires the presence of CD4(+) T cells capable of IFN-gamma
      synthesis.

PMID- 12186923
TI  - Development of a human neuronal cell model for human immunodeficiency virus (HIV)
      infected macrophage-induced neurotoxicity: apoptosis induced by HIV type 1
      primary isolates and evidence for involvement of the Bcl-2/Bcl-xL-sensitive
      intrinsic apoptosis pathway.
AB  - Neuronal apoptosis within the central nervous system (CNS) is a characteristic
      feature of AIDS dementia, and it represents a common mechanism of neuronal death
      induced by neurotoxins (e.g., glutamate) released from human immunodeficiency
      virus (HIV)-infected macrophages (HIV/macrophage-induced neurotoxicity). Neuronal
      apoptosis may result from activation of the intrinsic (mitochondrial/bcl-2
      regulated) or extrinsic (death receptor) pathways, although which pathway
      predominates in CNS HIV infection is unknown. Apoptosis initiated by the
      intrinsic pathway is typically blocked by antiapoptosis Bcl-2 family proteins,
      such as Bcl-2 and Bcl-xL, but whether these can block HIV/macrophage-induced
      neuronal apoptosis is unknown. To determine the potential role of the Bcl-2
      family in HIV/macrophage-induced neuronal apoptosis, we developed a unique in
      vitro model, utilizing the NT2 neuronal cell line, primary astrocytes and
      macrophages, and primary CNS HIV type 1 (HIV-1) isolates. We validated our model
      by demonstrating that NT2.N neurons are protected against HIV-infected
      macrophages by N-methyl-D-aspartate (NMDA) glutamate receptor antagonists,
      similar to effects seen in primary neurons. We then established stable NT2.N
      neuronal lines that overexpress Bcl-2 or Bcl-xL (NT2.N/bcl-2 and NT2.N/bcl-xL,
      respectively) and determined their sensitivity to macrophages infected with
      primary R5, X4, and R5/X4 HIV-1 isolates. We found that NT2.N/bcl-2 and NT2.N/bcl
      xL neurons were resistant to apoptosis induced by either R5, X4, or R5/X4
      isolates and that resistance was abrogated by a Bcl-2 antagonist. Thus, the NMDA
      receptor/bcl-2-regulated apoptotic pathway contributes significantly to
      HIV/macrophage-induced neuronal apoptosis, and Bcl-2 family proteins protect
      neurons against the spectrum of primary HIV-1 isolates. Modulation of bcl-2 gene
      expression may therefore offer adjunctive neuroprotection against development of
      AIDS dementia.

PMID- 12186924
TI  - The Epstein-Barr virus SM protein is functionally similar to ICP27 from herpes
      simplex virus in viral infections.
AB  - The herpes simplex virus type 1 (HSV-1) ICP27 protein is an essential RNA-binding
      protein that shuttles between the nucleus and cytoplasm to increase the
      cytoplasmic accumulation of viral late mRNAs. ICP27 homologs have been identified
      in each of the herpesvirus subfamilies, and accumulating evidence indicates that
      homologs from the gammaherpesvirus subfamily function similarly to ICP27. In
      particular, the Epstein-Barr virus (EBV) SM protein posttranscriptionally
      regulates gene expression, binds RNA in vitro and in vivo, and shuttles between
      the nucleus and cytoplasm. To determine if these two proteins function through a
      common mechanism, the ability of EBV SM to complement the growth defect of an HSV
      1 ICP27-null virus was examined in a transient-expression assay. ICP27 stimulated
      the growth of the null mutant more efficiently than did SM, but the ability of SM
      to compensate for the ICP27 defects suggests conservation of common functions. To
      assay for complementation in the context of a viral infection, the growth
      properties of an HSV recombinant expressing SM in an ICP27-null background were
      analyzed. SM stimulated growth of the recombinant, although this growth was
      reduced by comparison to that of an ICP27-expressing virus. By contrast, an HSV
      recombinant expressing an SM mutant allele defective for transactivation activity
      and nucleocytoplasmic shuttling did not grow at all. These results suggest that
      SM and ICP27 may regulate gene expression through a common pathway that is
      evolutionarily conserved in herpesviruses.

PMID- 12186925
TI  - Signals that dictate nuclear, nucleolar, and cytoplasmic shuttling of the
      gamma(1)34.5 protein of herpes simplex virus type 1.
AB  - The gamma(1)34.5 protein of herpes simplex virus type 1 (HSV-1) is required for
      viral neurovirulence in vivo. In infected cells, this viral protein prevents the
      shutoff of protein synthesis mediated by double-stranded-RNA-dependent protein
      kinase PKR. This is accomplished by recruiting protein phosphatase 1 to
      dephosphorylate the alpha subunit of translation initiation factor eIF-2 (eIF-2
      alpha). Moreover, the gamma(1)34.5 protein is implicated in viral egress and
      interacts with proliferating cell nuclear antigen. In this report, we show that
      the gamma(1)34.5 protein encoded by HSV-1(F) is distributed in the nucleus,
      nucleolus, and cytoplasm in transfected or superinfected cells. Deletion analysis
      revealed that the Arg-rich cluster from amino acids 1 to 16 in the gamma(1)34.5
      protein functions as a nucleolar localization signal. The region from amino acids
      208 to 236, containing a bipartite basic amino acid cluster, is able to mediate
      nuclear localization. R(215)A and R(216)A substitutions in the bipartite motif
      disrupt this activity. Intriguingly, leptomycin B, an inhibitor of nuclear
      export, blocks the cytoplasmic accumulation of the gamma(1)34.5 protein. L(134)A
      and L(136)A substitutions in the leucine-rich motif completely excluded the
      gamma(1)34.5 protein from the cytoplasm. These results suggest that the
      gamma(1)34.5 protein continuously shuttles between the nucleus, nucleolus, and
      cytoplasm, which may be a requirement for the different activities of the
      gamma(1)34.5 protein in virus-infected cells.

PMID- 12186927
TI  - The cauliflower mosaic virus virion-associated protein is dispensable for viral
      replication in single cells.
AB  - Cauliflower mosaic virus (CaMV) open reading frame III (ORF III) codes for a
      virion-associated protein (Vap), which is one of two viral proteins essential for
      aphid transmission. However, unlike the aphid transmission factor encoded by CaMV
      ORF II, Vap is also essential for systemic infection, suggesting that it is a
      multifunctional protein. To elucidate the additional function or functions of
      Vap, we tested the replication of noninfectious ORF III-defective mutants in
      transfected turnip protoplasts. PCR and Western blot analyses revealed that CaMV
      replication had occurred with an efficiency similar to that of wild-type virus
      and without leading to reversions. Electron microscopic examination revealed that
      an ORF III frameshift mutant formed normally structured virions. These results
      demonstrate that Vap is dispensable for replication in single cells and is not
      essential for virion morphogenesis. Analysis of inoculated turnip leaves showed
      that the ORF III frameshift mutant does not cause any detectable local infection.
      These results are strongly indicative of a role for Vap in virus movement.

PMID- 12186926
TI  - Homomultimerization of the coxsackievirus 2B protein in living cells visualized
      by fluorescence resonance energy transfer microscopy.
AB  - The 2B protein of enteroviruses is the viral membrane-active protein that is
      responsible for the modifications in host cell membrane permeability that take
      place in enterovirus-infected cells. The 2B protein shows structural similarities
      to the group of lytic polypeptides, polypeptides that permeate membranes either
      by forming multimeric membrane-integral pores or, alternatively, by lying
      parallel to the lipid bilayer and disturbing the curvature and symmetry of the
      membrane. Our aim is to gain more insight into the molecular architecture of the
      2B protein in vivo. In this study, the possible existence of multimers of the
      coxsackie B3 virus 2B protein in single living cells was explored by fluorescence
      resonance energy transfer (FRET) microscopy. FRET between fusion proteins 2B-ECFP
      and 2B-EYFP (enhanced cyan and yellow fluorescent variants of green fluorescent
      protein) was monitored by using spectral imaging microscopy (SPIM) and
      fluorescence lifetime imaging microscopy (FLIM). Both techniques revealed the
      occurrence of intermolecular FRET between 2B-ECFP and 2B-EYFP, providing evidence
      for the formation of protein 2B homomultimers. Putative models for the mode of
      action of the membrane-active 2B protein and the formation of membrane-integral
      pores by 2B multimers are discussed.

PMID- 12186929
TI  - Interaction with decay-accelerating factor facilitates coxsackievirus B infection
      of polarized epithelial cells.
AB  - All coxsackie B (CB) viruses can initiate infection by attaching to the
      coxsackievirus and adenovirus receptor (CAR). Although some CB isolates also bind
      to decay-accelerating factor (DAF), the role of DAF interaction during infection
      remains uncertain. We recently observed that CAR in polarized epithelial cells is
      concentrated at tight junctions, where it is relatively inaccessible to virus. In
      the experiments reported here we found that, unlike CAR, DAF was present on the
      apical surface of polarized cells and that DAF-binding isolates of CB3 and CB5
      infected polarized epithelial cells more efficiently than did isolates incapable
      of attaching to DAF. Virus attachment and subsequent infection of polarized cells
      by DAF-binding isolates were prevented in the presence of anti-DAF antibody.
      Serial passage on polarized cell monolayers selected for DAF-binding virus
      variants. Taken together, these results indicate that interaction with DAF on the
      apical surface of polarized epithelial cells facilitates infection by a subset of
      CB virus isolates. The results suggest a possible role for DAF in infection of
      epithelial cells at mucosal surfaces.

PMID- 12186928
TI  - Compartmentalization of surface envelope glycoprotein of human immunodeficiency
      virus type 1 during acute and chronic infection.
AB  - Human immunodeficiency virus type 1 is characterized by extensive genetic
      heterogeneity. Having previously demonstrated that, in the peripheral blood, the
      initial viral population is more homogeneous than at subsequent stages of
      infection, we have extended our studies to tissue samples, allowing comparisons
      between viral populations in peripheral blood and tissues during both the acute
      and chronic stages of infection. We found that homogeneity in gp120 sequences
      during the acute infection phase is not just restricted to the peripheral blood
      but also extends to other tissue compartments. However, in chronically infected
      individuals, heterogeneous and distinct viral populations were found in different
      compartments. We therefore conclude that the dominant and homogeneous viral
      population observed during the acute infection phase is likely to infiltrate
      lymphoid tissues and form the genetic bases for subsequent diversification. It is
      therefore likely that the compartmentalization of viral sequences observed in
      chronically infected patients reflects a gradual diversification of a common
      dominant viral variant rather than the preferential migration of distinct viral
      populations to different tissue compartments at the beginning of infection.

PMID- 12186930
TI  - Persistence of wild-type virus and lack of temporal structure in the latent
      reservoir for human immunodeficiency virus type 1 in pediatric patients with
      extensive antiretroviral exposure.
AB  - Although highly active antiretroviral therapy (HAART) for human immunodeficiency
      virus type 1 (HIV-1) infection can reduce levels of HIV-1 RNA in plasma to below
      the limit of detection, replication-competent forms of the virus persist in all
      infected individuals. One form of persistence involves a stable reservoir of
      latent but potentially infectious virus that resides in resting memory CD4(+) T
      cells. The mechanisms involved in maintaining this latent reservoir are
      incompletely understood. In the present study, we examined the dynamic
      characteristics of this reservoir in a cohort of children who developed drug
      resistant HIV-1 as a result of extensive exposure to inadequately suppressive one
      or two-drug regimens prior to the advent of HAART. We have previously shown that
      drug-resistant viruses selected by nonsuppressive pre-HAART regimens can enter
      and persist in this reservoir. We have extended these findings here by
      demonstrating that archival wild-type HIV-1 persists in this reservoir despite
      the fact that in these patients drug-resistant mutants have been favored by the
      selective conditions for many years. Phylogenetic analysis of replication
      competent viruses persisting in resting CD4(+) T cells revealed a striking lack
      of temporal structure in the sense that isolates obtained at later time points
      did not show greater sequence divergence than isolates from earlier time points.
      The persistence of drug-sensitive virus and the lack of temporal structure in the
      latent reservoir provide genetic evidence for the idea that HIV-1 can persist in
      a latent form free of selective pressure from antiretroviral drugs in long-lived
      resting memory CD4(+) T cells. Although there may be other mechanisms for viral
      persistence, this stable pool of latently infected cells is of significant
      concern because of its potential to serve as a lasting source of replication
      competent viruses, including the infecting wild-type form and all drug-resistant
      variants that have arisen subsequently.

PMID- 12186931
TI  - A recombinant rhesus cytomegalovirus expressing enhanced green fluorescent
      protein retains the wild-type phenotype and pathogenicity in fetal macaques.
AB  - To facilitate identification of rhesus cytomegalovirus (RhCMV)-infected cells, a
      recombinant virus expressing enhanced green fluorescent protein (EGFP),
      designated RhCMV-EGFP, was constructed. An expression cassette for EGFP under the
      control of the simian virus 40 (SV40) early promoter was inserted into the
      intergenic region between unique short 1 (US1) and US2 of the RhCMV genome by
      homologous recombination. RhCMV-EGFP exhibited comparable growth kinetics to that
      of wild-type virus in rhesus fibroblast cultures and retained its pathogenicity
      in monkey fetuses. Typical neurologic syndromes caused by CMV infection were
      observed in all fetuses experimentally inoculated with RhCMV-EGFP, as evidenced
      by sonographic and gross examinations. Systemic RhCMV infections were established
      in all fetuses, as viral antigen was detected in multiple organs and virus was
      isolated from fetal blood samples. The engineered viral genome was stable
      following rapid serial passages in vitro and multiple rounds of replication in
      vivo. Infected cells could be readily distinguished by green fluorescence both in
      tissue cultures and in the fetuses. In addition, EGFP expression was detected in
      various cell types that were permissive to RhCMV infection, consistent with a
      broad tissue tropism of the SV40 promoter. These results demonstrate that RhCMV
      can be successfully engineered without loss of wild-type replication and
      pathogenic potential. Further, the spectrum of cortical anomalies and the
      distribution of infected cells in the brain tissues indicated that RhCMV may have
      preferentially targeted immature neuronal cells. The pattern of RhCMV infection
      in the central nervous system may offer an explanation for the severe
      developmental outcomes associated with congenital human CMV infection early in
      gestation.

PMID- 12186932
TI  - Baculovirus transregulator IE1 requires a dimeric nuclear localization element
      for nuclear import and promoter activation.
AB  - Immediate-early protein IE1 is a principal regulator of viral transcription and a
      contributor to origin-specific DNA replication of the baculovirus Autographa
      californica multicapsid nucleopolyhedrovirus (AcMNPV). Since these viral
      functions involve interaction of dimeric IE1 with palindromic homologous region
      (hr) enhancer-origin elements of the AcMNPV genome within the nucleus, it is
      presumed that proper nuclear transport of IE1 is essential for productive
      infection. To investigate the mechanisms of IE1 nuclear import, we analyzed the
      effect of site-directed mutations on IE1 subcellular distribution. As
      demonstrated by fluorescence microscopy and biochemical fractionation of plasmid
      transfected cells, wild-type IE1 localized predominantly to the nucleus.
      Substitution or deletion of amino acid residues within a positively charged
      domain (residues 534 to 538) adjacent to IE1's oligomerization motif impaired
      nuclear import and caused loss of transactivation. Moreover, upon coexpression,
      these import-defective mutations prevented nuclear entry of wild-type IE1. In
      contrast, double-mutated IE1 defective for both nuclear import and dimerization
      failed to block nuclear entry or transactivation by wild-type IE1. Thus, import
      defective IE1 dominantly interfered with wild-type IE1 by direct interaction and
      cytosolic trapping. Collectively, our data indicate that the small basic domain
      encompassing residues R(537) and R(538) constitutes a novel nuclear localization
      element that functions only upon IE1 dimerization. These findings support a model
      wherein IE1 oligomerizes within the cytosol as a prerequisite for nuclear entry
      and subsequent high-affinity interaction with the symmetrical binding sites
      comprising AcMNPV hr enhancer-origin elements.

PMID- 12186933
TI  - Molecular evolution of hepatitis A virus: a new classification based on the
      complete VP1 protein.
AB  - Hepatitis A virus (HAV) is a positive-stranded RNA virus in the genus Hepatovirus
      in the family Picornaviridae So far, analysis of the genetic variability of HAV
      has been based on two discrete regions, the VP1/2A junction and the VP1 N
      terminus. In this report, we determined the nucleotide and deduced amino acid
      sequences of the complete VP1 gene of 81 strains from France, Kosovo, Mexico,
      Argentina, Chile, and Uruguay and compared them with the sequences of seven
      strains of HAV isolated elsewhere. Overall strain variation in the complete VP1
      gene was found to be as high as 23.7% at the nucleotide level and 10.5% at the
      amino acid level. Different phylogenetic methods revealed that HAV sequences form
      five distinct and well-supported genetic lineages. Within these lineages, HAV
      sequences clustered by geographical origin only for European strains. The
      analysis of the complete VP1 gene allowed insight into the mode of evolution of
      HAV and revealed the emergence of a novel variant with a 15-amino-acid deletion
      located on the VP1 region where neutralization escape mutations were found. This
      could be the first antigenic variant of HAV so far identified.

PMID- 12186935
TI  - The core of bluetongue virus binds double-stranded RNA.
AB  - Double-stranded RNA (dsRNA) viruses conceal their genome from the host to avoid
      triggering unfavorable cellular responses. The crystal structure of the core of
      one such virus, bluetongue virus, reveals an outer surface festooned with dsRNA.
      This may represent a deliberate strategy to sequester dsRNA released from damaged
      particles to prevent host cell shutoff.

PMID- 12186934
TI  - Induction and bypass of p53 during productive infection by polyomavirus.
AB  - Lytic infection by polyomavirus leads to elevated levels of p53 and induction of
      p53 target genes p21Cip1/WAF1 (p21) and BAX. This is seen both in polyomavirus
      infected primary mouse cell cultures and in kidney tissue of infected mice.
      Stabilization of p53 and induction of a p53 response are accompanied by
      phosphorylation of p53 on serine 18, mimicking a DNA damage response.
      Stabilization of p53 does not depend on p19Arf interaction with mdm2. Cells
      infected by a mutant virus defective in binding pRb and in inducing G(1)-to-S
      progression show a greatly diminished p53 response. However, cells infected by
      wild-type virus and blocked from entering S phase by addition of mimosine still
      show a p53 response. These results suggest a role of E2F target genes in inducing
      a p53 response. Polyomavirus large T antigen coprecipitates with p53
      phosphorylated on serine 18 and also with p21Cip1/WAF1. Implications of these and
      other findings on possible mechanisms of induction and override of p53 functions
      during productive infection by polyomavirus are discussed.

PMID- 12186936
TI  - Growth of rotaviruses in primary pancreatic cells.
AB  - Rotavirus infection in children at risk of developing type 1 diabetes has been
      temporally associated with development of pancreatic islet autoantibodies. In
      this study, nonobese diabetic mice were shown to be susceptible to rhesus
      rotavirus infection and pancreatic islets from nonobese diabetic mice, nonobese
      diabetes-resistant mice, fetal pigs, and macaque monkeys supported various
      degrees of rotavirus growth. Human rotaviruses replicated in monkey islets only.
      This islet susceptibility shows that rotavirus infection of the pancreas in vivo
      might be possible.

PMID- 12186937
TI  - Interferon regulatory factor 3 is a cellular partner of rotavirus NSP1.
AB  - The rotavirus nonstructural protein NSP1 is the least conserved protein in the
      rotavirus genome, and its function in the replication cycle is not known. We
      employed NSP1 as bait in the yeast two-hybrid interaction trap to identify
      candidate cellular partners of NSP1 that may provide clues to its function.
      Interferon regulatory factor 3 (IRF-3) was identified as an NSP1 interactor. NSP1
      synthesized in rotavirus-infected cells bound IRF-3 in a glutathione S
      transferase pull-down assay, indicating that the interaction was not unique to
      the two-hybrid system. NSP1 of murine rotavirus strain EW also interacted with
      IRF-3. NSP1 deletion and point mutants were constructed to map domains important
      in the interaction between NSP1 and IRF-3. The data suggest that a binding domain
      resides in the C terminus of NSP1 and that the N-terminal conserved zinc finger
      is important but not sufficient to mediate binding to IRF-3. We predict that a
      role for NSP1 in rotavirus-infected cells is to inhibit activation of IRF-3 and
      diminish the cellular interferon response.

PMID- 12186938
TI  - The human cytomegalovirus ribonucleotide reductase homolog UL45 is dispensable
      for growth in endothelial cells, as determined by a BAC-cloned clinical isolate
      of human cytomegalovirus with preserved wild-type characteristics.
AB  - An endothelial cell-tropic and leukotropic human cytomegalovirus (HCMV) clinical
      isolate was cloned as a fusion-inducing factor X-bacterial artificial chromosome
      in Escherichia coli, and the ribonucleotide reductase homolog UL45 was deleted.
      Reconstituted virus RVFIX and RV Delta UL45 grew equally well in human
      fibroblasts and human endothelial cells. Thus, UL45 is dispensable for growth of
      HCMV in both cell types.

PMID- 12186940
TI  - Calponin homology domains at a glance.

PMID- 12186939
TI  - Epstein-Barr virus latent membrane protein 2A regulates c-Jun protein through
      extracellular signal-regulated kinase.
AB  - Epstein-Barr virus (EBV) latent membrane protein 2A (LMP2A) is widely expressed
      in both EBV-infected cells and EBV-associated malignancies. However, the function
      of LMP2A is still veiled. In this study, LMP2A was found to induce the kinase
      activities of extracellular signal-regulated kinase (ERK) and c-Jun N-terminal
      kinase/stress-activated protein kinase JNK/SAPK. Furthermore, the downstream
      effector c-Jun showed hyperphosphorylation under LMP2A expression. The
      phosphorylation could be inhibited by the ERK pathway inhibitor PD98059,
      indicating that ERK may contribute to the phosphorylation of c-Jun in LMP2A
      expressing cells. The impact on c-Jun phosphorylation by mitogen-activated
      protein kinase (MAPK) is suggested to increase c-Jun protein stability, and this
      was also observed in LMP2A-expressing cells by a protein synthesis inhibition
      assay. Moreover, LMP2A-induced cell invasion was inhibited in the presence of the
      ERK pathway inhibitor. Taken together, we suggest that LMP2A may exploit MAPK
      kinases and affect both the phosphorylation and stability of c-Jun protein.
      Additionally, LMP2A may thereby promote the mobility of the cells. In doing so,
      it may enhance the mobility of EBV-infected cells and contribute to the
      metastatic process of malignant cells. Here we demonstrated the first evidence of
      LMP2A-induced migration and the underlying pathways accounting for it.

PMID- 12186941
TI  - Attachment and tension in the spindle assembly checkpoint.
AB  - Faithful transmission of chromosomes during mitosis is ensured by the spindle
      assembly checkpoint. This molecular safeguard examines whether prerequisites for
      chromosome segregation have been satisfied and thereby determines whether to
      execute or to delay chromosome segregation. Only when all the chromosomes are
      attached by kinetochore microtubules from two opposite spindle poles and proper
      tension is placed on the paired kinetochores does anaphase take place, allowing
      the physical splitting of sister chromatids. Recent studies have provided novel
      insights into the molecular mechanisms through which the spindle assembly
      checkpoint is regulated by both the attachment of chromosomes to kinetochore
      microtubules and the tension exerted on kinetochores.

PMID- 12186942
TI  - Calcium wave pacemakers in eggs.
AB  - During the past 25 years, the characterization of sperm-triggered calcium signals
      in eggs has progressed from the discovery of a single calcium increase at
      fertilization in the medaka fish to the observation of repetitive calcium waves
      initiated by multiple meiotic calcium wave pacemakers in the ascidian. In eggs of
      all animal species, sperm-triggered inositol (1,4,5)-trisphosphate
      [Ins(1,4,5)P(3)] production regulates the vast array of calcium wave patterns
      observed in the different species. The spatial organization of calcium waves is
      driven either by the intracellular distribution of the calcium release machinery
      or by the localized and dynamic production of calcium-releasing second
      messengers. In the highly polarized egg cell, cortical endoplasmic reticulum (ER)
      rich clusters act as pacemaker sites dedicated to the initiation of global
      calcium waves. The extensive ER network made of interconnected ER-rich domains
      supports calcium wave propagation throughout the egg. Fertilization triggers two
      types of calcium wave pacemakers depending on the species: in mice, the pacemaker
      site in the vegetal cortex of the egg is probably a site that has enhanced
      sensitivity to Ins(1,4,5)P(3); in ascidians, the calcium wave pacemaker may rely
      on a local source of Ins(1,4,5)P(3) production apposed to a cluster of ER in the
      vegetal cortex.

PMID- 12186943
TI  - aPKC kinase activity is required for the asymmetric differentiation of the
      premature junctional complex during epithelial cell polarization.
AB  - We have previously shown that aPKC interacts with cell polarity proteins PAR-3
      and PAR-6 and plays an indispensable role in cell polarization in the C. elegans
      one-cell embryo as well as in mammalian epithelial cells. Here, to clarify the
      molecular basis underlying this aPKC function in mammalian epithelial cells, we
      analyzed the localization of aPKC and PAR-3 during the cell repolarization
      process accompanied by wound healing of MTD1-A epithelial cells.
      Immunofluorescence analysis revealed that PAR-3 and aPKClambda translocate to
      cell-cell contact regions later than the formation of the primordial spot-like
      adherens junctions (AJs) containing E-cadherin and ZO-1. Comparison with three
      tight junction (TJ) membrane proteins, JAM, occludin and claudin-1, further
      indicates that aPKClambda is one of the last TJ components to be recruited.
      Consistently, the expression of a dominant-negative mutant of aPKClambda
      (aPKClambdakn) in wound healing cells does not inhibit the formation of the spot
      like AJs; rather, it blocks their development into belt-like AJs. These
      persistent spot-like AJs in aPKClambda-expressing cells contain all TJ membrane
      proteins and PAR-3, indicating that aPKC kinase activity is not required for
      their translocation to these premature junctional complexes but is indispensable
      for their further differentiation into belt-like AJs and TJs. Cortical bundle
      formation is also blocked at the intermediate step where fine actin bundles
      emanating from premature cortical bundles link the persistent spot-like AJs at
      apical tips of columnar cells. These results suggest that aPKC contributes to the
      establishment of epithelial cell polarity by promoting the transition of
      fibroblastic junctional structures into epithelia-specific asymmetric ones.

PMID- 12186944
TI  - Cytokinetic actomyosin ring formation and septation in fission yeast are
      dependent on the full recruitment of the polo-like kinase Plo1 to the spindle
      pole body and a functional spindle assembly checkpoint.
AB  - In dividing cells, the assembly and contraction of the cytokinetic actomyosin
      ring (CAR) is precisely coordinated with spindle formation and chromosome
      segregation. Despite having a cell wall, the fission yeast Schizosaccharomyces
      pombe forms a CAR reminiscent of the structure responsible for the cleavage of
      cells with flexible boundaries. We used the myo2-gc fission yeast strain in which
      the chromosomal copy of the type II myosin gene, myo2(+), is fused to the gene
      encoding green fluorescent protein (GFP) to investigate the dynamics of Myo2
      recruitment to the cytokinetic actomyosin ring in living cells. Analysis of CAR
      formation in relation to spindle pole body (SPB) and centromere separation
      enabled us to pinpoint the timing of Myo2 recruitment into a stable CAR structure
      to the onset of anaphase A. Depolymerisation of actin with latrunculin B did not
      affect the timing of Myo2 accumulation at the cell equator (although Myo2 no
      longer formed a ring), whereas depolymerisation of microtubules with either
      thiabendazole (TBZ) or methyl 2-benzimidazolecarbamate (MBC) resulted in a delay
      of up to 90 minutes in CAR formation. Microtubule depolymerisation also delayed
      the localisation of other CAR components such as actin and Mid1/Dmf1. The delay
      of cytokinesis in response to loss of microtubule integrity was abolished in
      cells lacking the spindle assembly checkpoint protein Mad2 or containing non
      functional Cdc16, a component of the fission yeast septation initiation network
      (SIN). The delay was also abolished in cells lacking Zfs1, a component of the
      previously described S. pombe cytokinesis checkpoint. Recruitment of the polo
      related kinase, Plo1, a key regulator of CAR formation, to the SPBs was
      substantially reduced in TBZ in a Mad2-dependent manner. Loading of Cdc7, a
      component of the SIN and downstream of Plo1 in the cytokinesis pathway, onto the
      the SPBs was also delayed in TBZ to the same extent as CAR formation. We conclude
      that CAR formation is subject to regulation by the spindle assembly checkpoint
      via the loading of Plo1 onto the SPBs and the consequent activation of the SIN.

PMID- 12186945
TI  - PKCalpha-mediated ERK, JNK and p38 activation regulates the myogenic program in
      human rhabdomyosarcoma cells.
AB  - We have previously suggested that PKCalpha has a role in 12-O
      Tetradecanoylphorbol-13-acetate (TPA)-mediated growth arrest and myogenic
      differentiation in human embryonal rhabdomyosarcoma cells (RD). Here, by
      monitoring the signalling pathways triggered by TPA, we demonstrate that PKCalpha
      mediates these effects by inducing transient activation of c-Jun N-terminal
      protein kinases (JNKs) and sustained activation of both p38 kinase and
      extracellular signal-regulated kinases (ERKs) (all referred to as MAPKs).
      Activation of MAPKs following ectopic expression of constitutively active
      PKCalpha, but not its dominant-negative form, is also demonstrated. We
      investigated the selective contribution of MAPKs to growth arrest and myogenic
      differentiation by monitoring the activation of MAPK pathways, as well as by
      dissecting MAPK pathways using MEK1/2 inhibitor (UO126), p38 inhibitor (SB203580)
      and JNK and p38 agonist (anisomycin) treatments. Growth-arresting signals are
      triggered either by transient and sustained JNK activation (by TPA and
      anisomycin, respectively) or by preventing both ERK and JNK activation (UO126)
      and are maintained, rather than induced, by p38. We therefore suggest a key role
      for JNK in controlling ERK-mediated mitogenic activity. Notably, sarcomeric
      myosin expression is induced by both TPA and UO126 but is abrogated by the p38
      inhibitor. This finding indicates a pivotal role for p38 in controlling the
      myogenic program. Anisomycin persistently activates p38 and JNKs but prevents
      myosin expression induced by TPA. In accordance with this negative role,
      reactivation of JNKs by anisomycin, in UO126-pre-treated cells, also prevents
      myosin expression. This indicates that, unlike the transient JNK activation that
      occurs in the TPA-mediated myogenic process, long-lasting JNK activation supports
      the growth-arrest state but antagonises p38-mediated myosin expression. Lastly,
      our results with the MEK inhibitor suggest a key role of the ERK pathway in
      regulating myogenic-related morphology in differentiated RD cells.

PMID- 12186947
TI  - A novel chk1-dependent G1/M checkpoint in fission yeast.
AB  - Fission yeast cells with a temperature-sensitive Orp1 protein, a component of the
      origin recognition complex, cannot perform DNA replication at the restrictive
      temperature. Seventy percent of orp1-4 cells arrest with a 1C DNA content,
      whereas 30% proceed to mitosis ('cut'). The arrest depends upon the checkpoint
      Rad proteins and, surprisingly, the Chk1 protein, which is thought to act only
      from late S phase. The arrested cells maintain a 1C DNA content, as judged by
      flow cytometry, and the early origin ars3001 has not been initiated, as judged by
      2D gel analysis. We show that in G1-arrested orp1-4 cells, Wee1 phosphorylates
      and inactivates Cdc2. Activation of Chk1 occurs earlier than Cdc2
      phosphorylation, indicating a novel role for Chk1, namely to induce and/or
      maintain Cdc2 phosphorylation upon checkpoint activation in G1. We also show that
      commitment to cutting occurs already in early G1 phase.

PMID- 12186946
TI  - Reduced IRS-2 and GLUT4 expression in PPARgamma2-induced adipocytes derived from
      C/EBPbeta and C/EBPdelta-deficient mouse embryonic fibroblasts.
AB  - In adipose tissue, the ability of cells to respond to insulin and to express
      genes such as those encoding fatty-acid-binding protein (422/aP2), lipoprotein
      lipase (LPL), adipsin and glucose transporter 4 (GLUT4) is acquired during their
      differentiation into mature adipocytes. It has been recognized that peroxisome
      proliferator-activated receptor gamma (PPARgamma) and CCAAT/enhancer-binding
      proteins (C/EBPs) play critical roles in adipocyte differentiation. However, it
      remained uncertain whether PPARgamma or which C/EBP is involved in the
      acquisition of these characteristics. We introduced PPARgamma2 into
      C/EBPbeta/delta-double deficient mouse embryonic fibroblasts (MEFs), followed by
      stimulation with its ligands, in order to define the roles of C/EBPbeta and
      C/EBPdelta in phenotypic acquisition during adipocyte differentiation. This
      procedure resulted in differentiation of these MEFs into mature adipocytes
      morphologically similar to wild-type MEFs. However, the adipocytes derived from
      the C/EBPbeta/delta-deficient MEFs showed lower expression of GLUT4 and adipsin
      mRNA than those derived from wild-type MEFs, although aP2 and LPL mRNA levels
      were similar in both types. The C/EBPbeta/delta-deficient adipocytes also
      expressed lower amounts of insulin receptor substrate 2 (IRS-2) than the
      adipocytes derived from wild-type MEFs, whereas the amounts of insulin receptor
      and IRS-1 were similar. Finally, insulin-responsive 2-deoxyglucose uptake was
      lower in the C/EBPbeta/delta-deficient cells. It could thus be demonstrated that
      C/EBPbeta and C/EBPdelta are involved in the acquisition of IRS-2 and GLUT4
      expression as well as in insulin-sensitive glucose uptake during adipocyte
      differentiation.

PMID- 12186948
TI  - Biosynthetic FGF-2 is targeted to non-lipid raft microdomains following
      translocation to the extracellular surface of CHO cells.
AB  - Basic fibroblast growth factor (FGF-2) is a secretory protein that lacks a signal
      peptide. Consistently, FGF-2 has been shown to be secreted by an ER-Golgi
      independent mechanism; however, the machinery mediating this process remains to
      be established at the molecular level. Here we introduce a novel experimental
      system based on flow cytometry that allows the quantitative assessment of non
      classical FGF-2 secretion in living cells. Stable cell lines have been created by
      retroviral transduction that express various kinds of FGF-2-GFP fusion proteins
      in a doxicyclin-dependent manner. Following induction of protein expression,
      biosynthetic FGF-2-GFP is shown to translocate to the outer surface of the plasma
      membrane as determined by both fluorescence activated cell sorting (FACS) and
      confocal microscopy. Both N- and C-terminal GFP tagging of FGF-2 is compatible
      with FGF-2 export, which is shown to occur in a controlled fashion rather than
      through unspecific release. The experimental system described has strong
      implications for the identification of both FGF-2 secretion inhibitors and
      molecular components involved in FGF-2 secretion. In the second part of this
      study we made use of the FGF-2 export system described to analyze the fate of
      biosynthetic FGF-2-GFP following export to the extracellular space. We find that
      secreted FGF-2 fusion proteins accumulate in large heparan sulfate proteoglycan
      (HSPG)-containing protein clusters on the extracellular surface of the plasma
      membrane. These microdomains are shown to be distinct from caveolae-like lipid
      rafts known to play a role in FGF-2-mediated signal transduction. Since CHO cells
      lack FGF high-affinity receptors (FGFRs), it can be concluded that FGFRs mediate
      the targeting of FGF-2 to lipid rafts. Consistently, FGF-2-GFP-secreting CHO
      cells do not exhibit increased proliferation activity. Externalization and
      deposition of biosynthetic FGF-2 in HSPG-containing protein clusters are
      independent processes, as a soluble secreted intermediate was demonstrated. The
      balance between intracellular FGF-2 and HSPG-bound secreted FGF-2 is shown not to
      be controlled by the availability of cell surface HSPGs, indicating that the FGF
      2 secretion machinery itself is rate-limiting.

PMID- 12186949
TI  - Changed lamellipodial extension, adhesion plaques and migration in epidermal
      keratinocytes containing constitutively expressed sense and antisense hyaluronan
      synthase 2 (Has2) genes.
AB  - Hyaluronan is a major component of the epidermal extracellular matrix, is
      actively synthesized by keratinocytes and shows fast matrix turnover in the
      stratified epithelium. We probed the importance of hyaluronan synthesis in
      keratinocytes by establishing cell lines carrying the exogenous hyaluronan
      synthase 2 (Has2) gene in sense and antisense orientations to increase and
      decrease their hyaluronan synthesis, respectively. Compared with cell lines
      transfected with the vector only, most clones containing the Has2 sense gene
      migrated faster in an in vitro wounding assay, whereas Has2 antisense cells
      migrated more slowly. Has2 antisense clones showed delayed entry into the S phase
      of cell cycle following plating, smaller lamellipodia and less spreading on the
      substratum. The decrease of hyaluronan on the undersurface of Has2 antisense
      cells was associated with an increased area of adhesion plaques containing
      vinculin. Exogenous hyaluronan added to the keratinocyte cultures had a minor
      stimulatory effect on migration after wounding but did not restore the reduced
      migratory ability of Has2 antisense cells. Hyaluronan decasaccharides that
      displace receptor bound hyaluronan in keratinocytes, and Streptomyces
      hyaluronidase sufficient to remove most cell surface hyaluronan had little effect
      on cell migration. The results suggest that the dynamic synthesis of hyaluronan
      directed by Has2, rather than the abundance of pericellular hyaluronan, controls
      keratinocyte migration, a cell function vital for the repair of squamous
      epithelia following wounding.

PMID- 12186950
TI  - Asy1, a protein required for meiotic chromosome synapsis, localizes to axis
      associated chromatin in Arabidopsis and Brassica.
AB  - The Arabidopsis thaliana ASY1 gene is essential for homologous chromosome
      synapsis. Antibodies specific to Asy1 protein and its homologue BoAsy1 from the
      related crop species Brassica oleracea have been used to investigate the temporal
      expression and localization of the protein in both species. Asy1 is initially
      detected in pollen mother cells during meiotic interphase as numerous punctate
      foci distributed over the chromatin. As leptotene progresses the signal appears
      to be increasingly continuous and is closely associated with the axial elements
      but not to the extended chromatin loops associated with them. By the end of
      zygotene the signal extends almost the entire length of the synapsed homologues,
      although not to the telomeres. The protein begins to disappear as the homologues
      desynapse, until by late diplotene it is no longer associated with the
      chromosomes. Immunogold labelling in conjunction with electron microscopy
      established that Asy1 localizes to regions of chromatin that associate with the
      axial/lateral elements of meiotic chromosomes rather than being a component of
      the synaptonemal complex itself. These data together with the previously observed
      asynaptic phenotype of the asy1 mutant suggest that Asy1 is required for
      morphogenesis of the synaptonemal complex, possibly by defining regions of
      chromatin that associate with the developing synaptonemal complex structure.

PMID- 12186951
TI  - Normal timing of oligodendrocyte development from genetically engineered, lineage
      selectable mouse ES cells.
AB  - Oligodendrocytes are post-mitotic cells that myelinate axons in the vertebrate
      central nervous system (CNS). They develop from proliferating oligodendrocyte
      precursor cells (OPCs), which arise in germinal zones, migrate throughout the
      developing white matter and divide a limited number of times before they
      terminally differentiate. Thus far, it has been possible to purify OPCs only from
      the rat optic nerve, but the purified cells cannot be obtained in large enough
      numbers for conventional biochemical analyses. Moreover, the CNS stem cells that
      give rise to OPCs have not been purified, limiting one's ability to study the
      earliest stages of commitment to the oligodendrocyte lineage. Pluripotent, mouse
      embryonic stem (ES) cells can be propagated indefinitely in culture and induced
      to differentiate into various cell types. We have genetically engineered ES cells
      both to positively select neuroepithelial stem cells and to eliminate
      undifferentiated ES cells. We have then used combinations of known signal
      molecules to promote the development of OPCs from selected, ES-cell-derived,
      neuroepithelial cells. We show that the earliest stages of oligodendrocyte
      development follow an ordered sequence that is remarkably similar to that
      observed in vivo, suggesting that the ES-cell-derived neuroepithelial cells
      follow a normal developmental pathway to produce oligodendrocytes. These
      engineered ES cells thus provide a powerful system to study both the mechanisms
      that direct CNS stem cells down the oligodendrocyte pathway and those that
      influence subsequent oligodendrocyte differentiation. This strategy may also be
      useful for producing human cells for therapy and drug screening.

PMID- 12186952
TI  - Functional involvement of VAMP/synaptobrevin-2 in cAMP-stimulated aquaporin 2
      translocation in renal collecting duct cells.
AB  - The involvement of soluble N-ethylmaleimide sensitive factor-attachment protein
      receptor (SNARE) proteins in the cAMP-induced exocytosis of aquaporin 2 (AQP2)
      containing vesicles was investigated in AQP2-transfected renal CD8 cells. RT-PCR
      and western blot analysis confirmed the presence of the SNARE homologs
      VAMP/synaptobrevin-2, syntaxin-1, syntaxin-4 and SNAP-23 in CD8 cells. Tetanus
      neurotoxin (TeNT) was efficient in cleaving synaptobrevin-like protein both in
      vitro and in intact CD8 cells incubated with the toxin. TeNT treatment in intact
      CD8 cells completely abolished cAMP-stimulated AQP2 targeting to the plasma
      membrane, as assessed by quantification of cell-surface immunoreactivity to an
      anti-AQP2 antibody raised against a peptide reproducing the extracellular AQP2 C
      loop. These results represent the first evidence for the functional involvement
      of VAMP-2 in cAMP-induced AQP2 exocytosis in renal cells.

PMID- 12186953
TI  - Evidence for a role for the Dictyostelium Rap1 in cell viability and the response
      to osmotic stress.
AB  - The Dictyostelium genome contains a single rapA gene, which encodes a Rap1
      monomeric G protein. As attempts at generating rapA-null Dictyostelium cells had
      been unsuccessful, expression of antisense RNA from the rapA gene under control
      of the folate repressible discoidin promoter was used to reduce cellular levels
      of the Rap1 protein. As Rap1 levels gradually decreased following antisense rapA
      RNA induction, growth rate and cell viability also decreased, a result consistent
      with the idea that rapA is an essential gene. The Rap1-depleted cells exhibited
      reduced viability in response to osmotic shock. The accumulation of cGMP in
      response to 0.4 M sorbitol was reduced after rapA antisense RNA induction and was
      enhanced in cells expressing the constitutively activated Rap1(G12V) protein,
      suggesting a role for Rap1 in the generation of cGMP. Dictyostelium Rap1 formed a
      complex with the Ras-binding domain of RalGDS only when it was in a GTP-bound
      state. This assay was used to demonstrate that activation of Rap1 in response to
      0.4 M sorbitol occurred with initial kinetics similar to those observed for the
      accumulation of cGMP. Furthermore, the addition of 2 mM EDTA to osmotically
      shocked cells, a treatment that enhances cGMP accumulation, also enhanced Rap1
      activation. These results suggest a direct role for Rap1 in the activation of
      guanylyl cyclase during the response to hyperosmotic conditions. Rap1 was also
      activated in response to low temperature but not in response to low osmolarity or
      high temperature.

PMID- 12186954
TI  - Binding of Sly1 to Sed5 enhances formation of the yeast early Golgi SNARE
      complex.
AB  - SLY1 is an essential gene for vesicular transport between the ER and the early
      Golgi apparatus in Saccharomyces cerevisiae. It encodes a hydrophilic Sec1/Munc18
      family protein that binds to the t-SNAREs. The amount of Sly1 protein that
      coprecipitated with the t-SNARE Sed5 was much reduced in a temperature-sensitive
      sly1(ts) mutant yeast compared with the wildtype. The mutant Sly1(ts) protein was
      shown to have a reduced binding activity to Sed5. In the wildtype, a detectable
      amount of Sly1 was found in the complex between Sed5 and the v-SNARE Bet1. In
      vitro formation of this complex on different membranes in yeast lysate was
      enhanced by the addition of recombinant Sly1. These results indicate that binding
      of Sly1 to Sed5 enhances trans-SNARE complex formation.

PMID- 12186955
TI  - Diverting intracellular trafficking of Salmonella to the lysosome through
      activation of the late endocytic Rab7 by intracellular delivery of muramyl
      dipeptide.
AB  - Previously, we showed that live Salmonella-containing phagosomes (LSP) recruit
      early acting Rab5 and promote fusion with early endosomes, thus avoiding
      transport to the lysosomes. Therefore, live Salmonella survive in a specialized
      compartment. Here we show that scavenger-receptor-mediated intracellular delivery
      of muramyl dipeptide (MDP) to macrophages leads to efficient killing of
      Salmonella both in vitro and in vivo. To understand the intracellular trafficking
      modulation of Salmonella by delivery of MDP, we investigated the levels of
      endocytic Rab proteins, which are the major regulators of vesicular transport.
      Western blot analysis reveals reduced Rab5 and enhanced Rab7 content in the
      maleylated bovine serum albumin-MDP (MBSA-MDP)-treated cells. The reduced content
      of Rab5 in the treated cells and on phagosomes inhibits the fusion of Salmonella
      containing phagosomes with early endosomes, and the enhanced Rab7 content in
      these cells facilitated targeting of LSP to lysosomes, which contain cathepsin D
      and vacuolar ATPase, for killing. In vitro reconstitution of lysosomal transport
      demonstrated that a reduced content of Rab5 and an enhanced level of Rab7 in MBSA
      MDP-treated cells is primarily responsible for targeting Salmonella to lysosomes.
      Intracellular delivery of MDP thus offers a general strategy against macrophage
      associated infections caused by intracellular pathogens that survive in the host
      cell by resisting transport to lysosomes.

PMID- 12186956
TI  - RabD, a Dictyostelium Rab14-related GTPase, regulates phagocytosis and homotypic
      phagosome and lysosome fusion.
AB  - RabD, a Dictyostelium Rab14-related GTPase, localizes in the endo-lysosomal
      pathway and contractile vacuole system of membranes. Cell lines expressing
      dominant-negative RabD were defective in endocytosis, endosomal membrane flow and
      homotypic lysosome fusion. In support of a role for RabD in fusion, cells
      overexpressing constitutively active RabD(Q67L) accumulated enlarged hydrolase
      rich acidic vesicles ringed with GFP-RabD, consistent with RabD directly
      regulating lysosome fusion. To determine whether RabD also regulated phagocytosis
      and/or homotypic phagosome fusion (a process stimulated by many intracellular
      pathogens), cells overexpressing dominant-active (RabD(Q67L)) or dominant
      negative (Rab(N121I)) RabD were analyzed microscopically and biochemically. The
      rate of phagocytosis was increased two-fold in RabD(Q67L)-expressing cells and
      reduced by 50% in RabD(N121I)-expressing cells compared with control cells. To
      examine the role of RabD in the formation of multiparticle phagosomes, we
      performed a series of pulse-chase experiments using fluorescently labeled
      bacteria and fluorescent latex beads. The rate of fusion of newly formed
      phagosomes was five times higher in the RabD(Q67L)-expressing cells and reduced
      by over 50% in RabD(N121I)-expressing cells as compared with control cells. GFP
      RabD(Q67L) was found to ring multiparticle spacious phagosomes, which supports a
      direct role for this protein in regulating fusion. Inhibition of PI 3-kinase
      activity, which is known to regulate phagosome fusion in the wild-type cells,
      reduced the rate of phagosome fusion in RabD(Q67L+) cells, indicating that RabD
      acted upstream of or parallel with PI 3-kinase. We hypothesize that RabD and,
      possibly, Rab14, a related GTPase that associates with phagosomes in mammalian
      cells, are important regulators of homotypic phagosome and endo-lysosome fusion.

PMID- 12186959
TI  - Techniques for using Bexxar for the treatment of non-Hodgkin's lymphoma.
AB  - OBJECTIVE: This article briefly describes the concept of radioimmunotherapy and
      treatment of non-Hodgkin's lymphoma by a new radiopharmaceutical that uses this
      technique. The rationale for such an approach is reviewed, and some of the
      practical consequences for technologists are examined. These include the idea of
      performing individually customized dosimetry and using relatively high (131)I
      doses on an outpatient basis. After reading this article, the nuclear medicine
      technologist should be able to (a) describe radioimmunotherapy and its
      advantages, (b) explain why treatment of non-Hodgkin's lymphoma is enhanced by
      this technique, (c) understand the role of the predose study and its use in
      determining the therapeutic dose, and (d) recognize the radiation safety issues
      involved with the therapeutic dose administration and patient release criteria.

PMID- 12186960
TI  - Detecting regional cerebral blood flow changes in Alzheimer's patients after
      milameline treatment: activation or baseline SPECT?
AB  - The purpose of this study was to evaluate the effectiveness of activation versus
      baseline SPECT in detecting the regional cerebral blood flow (rCBF) changes in
      Alzheimer's disease (AD) patients after milameline (CI979/RU35926) treatment.
      METHODS: Ten patients with AD who took part in a milameline drug trial were
      examined by (99m)Tc-hexamethylpropyleneamine oxime SPECT before and after the
      medication. A split-dose technique was used for the acquisition of baseline and
      activation images within a single session. Two patients were unable to complete
      the activation challenges. rCBF changes were assessed using the statistical
      parametric mapping program. Both increased and decreased contrasts were used to
      test rCBF changes on activation and baseline images, respectively. rCBF changes
      caused by activation were also examined before and after milameline treatment.
      RESULTS: Decreased rCBFs were observed at the temporal cortex on both sides of
      the brain and at the left parietal cortex on the activation SPECT images after
      milameline, whereas no statistically significant rCBF change was found on the
      baseline SPECT images. Memory stress caused not only increased rCBF in many areas
      of the brain, including the parietotemporal cortex, but also decreased rCBF at
      the splenium of the corpus callosum. CONCLUSION: Cognitive activation scans are
      more effective than baseline scans in detecting rCBF changes in AD patients after
      milameline.

PMID- 12186961
TI  - Serum caffeine levels after 24-hour abstention: clinical implications on
      dipyridamole (201)Tl myocardial perfusion imaging.
AB  - BACKGROUND: Caffeine binds to the A2 receptors and inhibits adenosine's action of
      vasodilation or dipyridamole-induced vasodilation. Patients scheduled for (201)Tl
      myocardial perfusion using pharmacologic stress with dipyridamole or adenosine
      are advised to abstain from caffeine for 24 h before the test. This article
      reports on the residual serum caffeine levels of 36 patients after 24-h caffeine
      abstention and the clinical implications on dipyridamole (201)Tl myocardial
      perfusion imaging. METHODS AND RESULTS: Heart rate, diastolic blood pressure, and
      systolic blood pressure were recorded before and after dipyridamole infusion.
      Sixty-six percent of the patients had detectable plasma caffeine but all values
      were within the range of 0.1-0.8 mg/L. No statistically significant change in
      diastolic and systolic blood pressures after dipyridamole infusion has been
      observed. The mean heart rate was increased by 18% after dipyridamole infusion in
      patients with zero caffeine, and the heart rate increase was inversely correlated
      with the serum caffeine levels (r = -0.22) with 81% confidence. CONCLUSION: A
      serum caffeine level of 2 mg/L is predicted to be the lower limit for false
      negative dipyridamole (201)Tl myocardial perfusion. The increase of heart rate
      after dipyridamole infusion could be the simple indicator for the serum caffeine
      level. Rescheduling of the patient study or further adenosine challenge is
      necessary only if the heart rate increase is <5% after dipyridamole or adenosine
      infusion.

PMID- 12186962
TI  - Penile implant on bone scan imaging: a case study.
AB  - We present an unusual case of the incidental finding of a penile implant on a
      whole-body bone scan obtained for back pain in a patient with osteoporosis and
      vertebral body fractures. On 2 separate occasions, this patient underwent 3-h
      delayed whole-body bone scanning with (99m)Tc-methylene diphosphonate. The images
      showed acute and then subacute vertebral body fractures. On both imaging
      occasions, the bone scan that included the region of the implant clearly showed
      the penis, but visualization was better on the second scan. Penile implants have
      not been described in the nuclear medicine literature, and it is important to
      recognize the diagnostic possibilities when penile photopenia is identified.

PMID- 12186970
TI  - Dynamic and clustering model of bacterial chemotaxis receptors: structural basis
      for signaling and high sensitivity.
AB  - Bacterial chemotaxis receptors can detect a small concentration gradient of
      attractants and repellents in the environment over a wide range of background
      concentration. The clustering of these receptors to form patches observed in vivo
      and in vitro has been suspected as a reason for the high sensitivity, and such
      wide dynamic range is thought to be due to the resetting of the receptor
      sensitivity threshold by methylation/demethylation of the receptors. However, the
      mechanisms by which such high sensitivity is achieved and how the
      methylation/demethylation resets the sensitivity are not well understood. A
      molecular modeling of an intact bacterial chemotaxis receptor based on the
      crystal structures of a cytoplasmic domain and a periplasmic domain suggests an
      interesting clustering of three dimeric receptors and a two-dimensional, close
      packed lattice formation of the clusters, where each receptor dimer contacts two
      other receptor dimers at the cytoplasmic domain and two yet different receptor
      dimers at the periplasmic domain. This interconnection of the receptors to form a
      patch of receptor clusters suggests a structural basis for the high sensitivity
      of the bacterial chemotaxis receptors. Furthermore, we present crystallographic
      data suggesting that, in contrast to most molecular signaling by conformational
      changes and/or oligomerization of the signaling molecules, the changes in dynamic
      property of the receptors on ligand binding or methylation may be the language of
      the signaling by the chemotaxis receptors. Taken together, the changes of the
      dynamic property of one receptor propagating mechanically to many others in the
      receptor patch provides a plausible, simple mechanism for the high sensitivity
      and the dynamic range of the receptors.

PMID- 12186971
TI  - CD8(+) T cell responses against a dominant cryptic HLA-A2 epitope after NY-ESO-1
      peptide immunization of cancer patients.
AB  - NY-ESO-1 is a germ cell antigen aberrantly expressed in different tumor types
      that elicits strong humoral and cellular immune responses in cancer patients.
      Monitoring spontaneous CD8(+) T cell responses against NY-ESO-1 peptides 157-165
      (S9C) and 157-167 (S11L) in a series of HLA-A2(+) cancer patients showed that
      these two peptides had overlapping antigenic profiles and were equally
      immunogenic. However, discrepancies between S9C and S11L reactivities were
      observed upon vaccination with both peptides to generate or boost T cell
      responses to NY-ESO-1 in cancer patients. We here analyze the fine specificity of
      these responses and describe an HLA-A2-restricted epitope, NY-ESO-1 peptide 159
      167 (L9L), which is strongly recognized by CD8(+) T cells as a result of peptide
      vaccination of cancer patients. Responses to L9L were stimulated by S11L and
      appeared early in the course of vaccination, independently of S9C responses.
      However, L9L-specific CD8(+) T cells failed to recognize tumor cells naturally
      expressing NY-ESO-1 or B lymphoblastoid cells transduced with NY-ESO-1.
      Processing of L9L could be rescued after IFN-gamma treatment of tumor cells or by
      dendritic cells pulsed with NY-ESO-1 protein/antibody immune complexes. The
      present results demonstrate a dual specificity within peptide S11L, with S9C as
      the natural antigenic tumor epitope, and L9L as a cryptic epitope with dominant
      immunogenicity upon vaccination that diverts the immune response from tumor
      recognition. These unanticipated findings raise questions about the use of S11L
      in the clinic and emphasize the importance of analyzing the fine specificity of
      vaccine-induced T cell responses in patients as a basis for constructing
      effective cancer vaccines.

PMID- 12186972
TI  - Phytochrome from Agrobacterium tumefaciens has unusual spectral properties and
      reveals an N-terminal chromophore attachment site.
AB  - Phytochromes are photochromic photoreceptors with a bilin chromophore that are
      found in plants and bacteria. The soil bacterium Agrobacterium tumefaciens
      contains two genes that code for phytochrome-homologous proteins, termed
      Agrobacterium phytochrome 1 and 2 (Agp1 and Agp2). To analyze its biochemical and
      spectral properties, Agp1 was purified from the clone of an E. coli
      overexpressor. The protein was assembled with the chromophores phycocyanobilin
      and biliverdin, which is the putative natural chromophore, to photoactive
      holoprotein species. Like other bacterial phytochromes, Agp1 acts as light
      regulated His kinase. The biliverdin adduct of Agp1 represents a previously
      uncharacterized type of phytochrome photoreceptor, because photoreversion from
      the far-red absorbing form to the red-absorbing form is very inefficient, a
      feature that is combined with a rapid dark reversion. Biliverdin bound covalently
      to the protein; blocking experiments and site-directed mutagenesis identified a
      Cys at position 20 as the binding site. This particular position is outside the
      region where plant and some cyanobacterial phytochromes attach their chromophore
      and thus represents a previously uncharacterized binding site. Sequence
      comparisons imply that the region around Cys-20 is a ring D binding motif in
      phytochromes.

PMID- 12186973
TI  - Protein-DNA computation by stochastic assembly cascade.
AB  - The assembly of RecA on single-stranded DNA is measured and interpreted as a
      stochastic finite-state machine that is able to discriminate fine differences
      between sequences, a basic computational operation. RecA filaments efficiently
      scan DNA sequence through a cascade of random nucleation and disassembly events
      that is mechanistically similar to the dynamic instability of microtubules. This
      iterative cascade is a multistage kinetic proofreading process that amplifies
      minute differences, even a single base change. Our measurements suggest that this
      stochastic Turing-like machine can compute certain integral transforms.

PMID- 12186974
TI  - A nonsense mutation in the gene encoding 2'-5'-oligoadenylate synthetase/L1
      isoform is associated with West Nile virus susceptibility in laboratory mice.
AB  - A mouse model has been established to investigate the genetic determinism of host
      susceptibility to West Nile (WN) virus, a member of the genus flavivirus and
      family Flaviviridae. Whereas WN virus causes encephalitis and death in most
      laboratory inbred mouse strains after peripheral inoculation, most strains
      derived from recently trapped wild mice are completely resistant. The phenotype
      of resistance/susceptibility is determined by a major locus, Wnv, mapping to
      chromosome 5 within the 0.4-cM-wide interval defined by markers D5Mit408 and
      D5Mit242. We constructed a high resolution composite/consensus map of the
      interval by merging the data from the mouse T31 Radiation Hybrid map and those
      from the homologous region of human chromosome 12q, and found the cluster of
      genes encoding 2'-5'-oligoadenylate synthetases (2'-5'-OAS) to be the most
      prominent candidate. This cluster encodes a multimember family of IFN-inducible
      proteins that is known to play an important role in the established endogenous
      antiviral pathway. Comparing the cDNA sequences of 2'-5'-OAS L1, L2, and L3
      isoforms, between susceptible and resistant strains, we identified a STOP codon
      in exon 4 of the gene encoding the L1 isoform in susceptible strains that can
      lead to a truncated form with amputation of one domain, whereas all resistant
      mice tested so far have a normal copy of this gene. The observation that WN virus
      sensitivity of susceptible mice was completely correlated with the occurrence of
      a point mutation in 2'-5'-OAS L1 suggests that this isoform may play a critical
      role in WN pathogenesis.

PMID- 12186975
TI  - SALSA, a variant of yeast SAGA, contains truncated Spt7, which correlates with
      activated transcription.
AB  - Spt-Ada-Gcn5 acetyltransferase (SAGA) is a previously described histone
      acetyltransferase/transcriptional coactivator complex in yeast. At promoters of
      certain genes (HIS3 and TRP3), SAGA has an inhibitory function involving a
      nonproductive TATA-binding protein interaction mediated by the Spt3 and Spt8
      subunits. Related to this, Spt8-less SAGA is a major form of the complex under
      activating conditions for these genes. In the present study, we purify this
      activation-specific complex, called SALSA (SAGA altered, Spt8 absent). Besides
      lacking Spt8, SALSA contains Spt7 subunit that is truncated. Examining the role
      of this subunit, we find that C-terminally truncated SPT7 resulted in derepressed
      HIS3 transcription. Furthermore, when grown in rich media (repressing
      conditions), wild-type cells yielded predominantly SAGA, but Spt7 C-terminal
      truncations resulted primarily in a form of complex similar to SALSA. Thus, SALSA
      like structure and activating function can be partially recapitulated in yeast by
      truncating the C terminus of Spt7. Overall, these results lead to a model that
      for a subset of promoters SAGA is inhibitory through Spt3, Spt8, and an Spt8
      interacting subdomain of Spt7, whereas SALSA is a form of complex for positive
      transcriptional regulation. These data clarify a mechanism by which a
      transcriptional regulatory complex can switch between positive and negative
      modulation.

PMID- 12186977
TI  - Probing the transition state via photoelectron and photodetachment spectroscopy
      of H(3)O(-).
AB  - The H(3)O(-) anion has stable and metastable structures that resemble
      configurations in the vicinity of the transition state for the neutral reactions
      OH + H(2) <--> H(2)O + H. Photoelectron spectroscopy of this anion probes the
      neutral reaction dynamics in the critical transition-state region. Accurate
      quantum dynamics calculations of the photoelectron intensity and
      photodissociation product energies are shown to provide a quantitatively reliable
      means of interpreting such experimental observations and reveal a detailed
      picture of the reaction dynamics.

PMID- 12186976
TI  - Huntington's disease age-of-onset linked to polyglutamine aggregation nucleation.
AB  - In Huntington's Disease and related expanded CAG repeat diseases, a polyglutamine
      [poly(Gln)] sequence containing 36 repeats in the corresponding disease protein
      is benign, whereas a sequence with only 2-3 additional glutamines is associated
      with disease risk. Above this threshold range, longer repeat lengths are
      associated with earlier ages-of-onset. To investigate the biophysical basis of
      these effects, we studied the in vitro aggregation kinetics of a series of
      poly(Gln) peptides. We find that poly(Gln) peptides in solution at 37 degrees C
      undergo a random coil to beta-sheet transition with kinetics superimposable on
      their aggregation kinetics, suggesting the absence of soluble, beta-sheet-rich
      intermediates in the aggregation process. Details of the time course of aggregate
      growth confirm that poly(Gln) aggregation occurs by nucleated growth
      polymerization. Surprisingly, however, and in contrast to conventional models of
      nucleated growth polymerization of proteins, we find that the aggregation nucleus
      is a monomer. That is, nucleation of poly(Gln) aggregation corresponds to an
      unfavorable protein folding reaction. Using parameters derived from the kinetic
      analysis, we estimate the difference in the free energy of nucleus formation
      between benign and pathological length poly(Gln)s to be less than 1 kcal/mol. We
      also use the kinetic parameters to calculate predicted aggregation curves for
      very low concentrations of poly(Gln) that might obtain in the cell. The repeat
      length-dependent differences in predicted aggregation lag times are in the same
      range as the length-dependent age-of-onset differences in Huntington's disease,
      suggesting that the biophysics of poly(Gln) aggregation nucleation may play a
      major role in determining disease onset.

PMID- 12186978
TI  - Essential myosin light chain as a target for caspase-3 in failing myocardium.
AB  - Programmed cell death involves the activation of caspase proteases that can
      mediate the cleavage of vital cytoskeletal proteins. We have recently reported
      that, in failing cardiac myocytes, caspase-3 activation is associated with a
      reduction in contractile performance. In this study we used a modified yeast two
      hybrid system to screen for caspase-3 interacting proteins of the cardiac
      cytoskeleton. We identified ventricular essential myosin light chain (vMLC1) as a
      target for caspase-3. By sequencing and site-directed mutagenesis, a noncanonical
      cleavage site for caspase-3 was mapped to the C-terminal DFVE(135)G motif. We
      demonstrated that vMLC1 cleavage in failing myocardium in vivo is associated with
      a morphological disruption of the organized vMLC1 staining of sarcomeres, and
      with a reduction in myocyte contractile performance. Adenoviral gene transfer of
      the caspase inhibitor p35 in vivo prevented caspase-3 activation and vMLC1
      cleavage, with positive impact on contractility. These data suggest that direct
      cleavage of vMLC1 by activated caspase-3 may contribute to depression of myocyte
      function by altering cross-bridge interaction between myosin and actin molecules.
      Therefore, activation of apoptotic pathways in the heart may lead to contractile
      dysfunction before cell death.

PMID- 12186979
TI  - Evidence for an ancient selective sweep in the MHC class I gene repertoire of
      chimpanzees.
AB  - MHC class I molecules play an essential role in the immune defense against
      intracellular infections. The hallmark of the MHC is its extensive degree of
      polymorphism at the population level. However, the present comparison of MHC
      class I gene intron variation revealed that chimpanzees have experienced a severe
      repertoire reduction at the orthologues of the HLA-A, -B, and -C loci. The loss
      of variability predates the (sub)speciation of chimpanzees and did not effect
      other known gene systems. Therefore the selective sweep in the MHC class I gene
      may have resulted from a widespread viral infection. Based on the present results
      and the fact that chimpanzees have a natural resistance to the development of
      AIDS, we hypothesize that the selective sweep was caused by the chimpanzee
      derived simian immunodeficiency virus (SIVcpz), the closest relative of HIV-1, or
      a closely related retrovirus. Hence, the contemporary chimpanzee populations
      represent the offspring of AIDS-resistant animals, the survivors of a HIV-like
      pandemic that took place in the distant past.

PMID- 12186982
TI  - Psychiatric morbidity amongst infertile Chinese women undergoing treatment with
      assisted reproductive technology and the impact of treatment failure.
AB  - This is a prospective study to assess the psychiatric morbidity in Chinese
      infertile women who underwent treatments with assisted reproductive technology
      and also the impact of treatment failure. The 30-item General Health
      Questionnaire (GHQ) and the Beck Depression Inventory (BDI) were employed before
      and 3 weeks after the assisted reproductive technology treatment. Data from 372
      patients who completed the questionnaires and failed the treatment were analyzed.
      Before treatment, 33% of the participants scored above the GHQ cutoff, and 8% had
      a BDI score of 20 or above, signifying moderate to severe depression. Following
      failed treatment, 43% scored above GHQ cutoff, and 8% had BDI scores 20 or above.
      The posttreatment GHQ and BDI scores were significantly higher than the
      corresponding scores at baseline (p < 0.001). About 13% of the participants
      reported self-harm ideas. The severity of depression following a failed treatment
      was positively associated with the duration of infertility (p < 0.05), but not
      with the posttreatment BDI scores, age, education, and number of previous
      treatment episodes. Our results show that one third of the women who sought
      infertility treatment had an impaired psychological well-being. Following failed
      treatment, there was a further deterioration in mental health, and about 10% of
      the participants were moderately to severely depressed. Proper psychological care
      and counseling should be an integral part of infertility management among the
      Chinese population.

PMID- 12186981
TI  - Physiology meets biophysics: visualizing the interaction of hypoxia-inducible
      factor 1 alpha with p300 and CBP.

PMID- 12186980
TI  - The expression of growth hormone-releasing hormone (GHRH) and splice variants of
      its receptor in human gastroenteropancreatic carcinomas.
AB  - Splice variants (SVs) of receptors for growth hormone-releasing hormone (GHRH)
      have been found in primary human prostate cancers and diverse human cancer cell
      lines. GHRH antagonists inhibit growth of various experimental human cancers,
      including pancreatic and colorectal, xenografted into nude mice or cultured in
      vitro, and their antiproliferative action could be mediated in part through SVs
      of GHRH receptors. In this study we examined the expression of mRNA for GHRH and
      for SVs of its receptors in tumors of human pancreatic, colorectal, and gastric
      cancer cell lines grown in nude mice. mRNA for both GHRH and SV(1) isoform of
      GHRH receptors was expressed in tumors of pancreatic (SW1990, PANC-1, MIA PaCa-2,
      Capan-1, Capan-2, and CFPAC1), colonic (COLO 320DM and HT-29), and gastric (NCI
      N87, HS746T, and AGS) cancer cell lines; mRNA for SV(2) was also present in Capan
      1, Capan-2, CFPAC1, HT-29, and NCI-N87 tumors. In proliferation studies in vitro,
      the growth of pancreatic, colonic, and gastric cancer cells was stimulated by
      GHRH(1-29)NH(2) and inhibited by GHRH antagonist JV-1-38. The stimulation of some
      gastroenteropancreatic cancer cells by GHRH was followed by an increase in cAMP
      production, and GHRH antagonist JV-1-38 competitively inhibited this effect. Our
      study indicates the presence of an autocrine/paracrine stimulatory loop based on
      GHRH and SV(1) of GHRH receptors in human pancreatic, colorectal, and gastric
      cancers. The finding of SV(1) receptor in human cancers provides an approach to
      an antitumor therapy based on the blockade of this receptor by specific GHRH
      antagonists.

PMID- 12186983
TI  - The cardiovascular risk factor homocysteine is not elevated in young women with
      hyperandrogenism or hypoestrogenism.
AB  - The aim of the present study was to determine whether the plasma concentrations
      of homocysteine (Hcy) are elevated in women with hypogonadotropic hypogonadism (a
      condition of chronic hypoestrogenism) and in women with polycystic ovarian
      syndrome (PCOS, a syndrome characterized by hyperandrogenemia). A cross-sectional
      study was performed. The plasma concentrations of Hcy were determined in 12
      normal-cycling women, in 14 women with hypogonadotropic amenorrhea (HA), and in
      20 women with PCOS. The plasma LH, FSH, E(2), testosterone, free testosterone,
      and androstenedione levels were measured. The blood samples analyzed were taken
      during the early follicular phase in controls and without regard to the menstrual
      phase in the patients. Twelve normal-cycling women were compared with 14 women
      with HA and with 20 women with PCOS. Women with HA or PCOS have plasma
      concentrations of Hcy similar to those of healthy women with normal menstrual
      cycles. The results suggest that young women with chronic hypoestrogenism (HA) or
      hyperandrogenism (PCOS) have plasma concentrations of Hcy similar to those of
      healthy women with normal menstrual cycles.

PMID- 12186984
TI  - Magnetic resonance imaging and endometriosis: deeply infiltrating endometriosis
      does not originate from the rectovaginal septum.
AB  - The goal of this study was to describe the magnetic resonance (MR) imaging signs
      of deeply infiltrating endometriosis (DIE) lesions and above all to find out if
      MR imaging can pinpoint the location of these lesions. We made a retrospective
      study of 8 patients presenting with histologically proven DIE lesions. The MR
      imaging results were compared with intraoperative findings. Nodules revealed on
      T1-weighted images as isointense to myometrium with hyperintense spots remained
      visible on the fat-suppressed spin echo images. When there was no rectal
      involvement, the T1- and T2-weighted images showed a hypointense transition area
      between the nodule and the rectum. The DIE nodules were in identical locations in
      every case, lying below the torus uterinum, level with the posterior vaginal
      fornix and the upper third of the posterior vaginal wall. Without exception, the
      DIE nodules were located above the upper edge of the rectovaginal septum, with
      the latter appearing fine and regular with no image of any nodule. Our MR imaging
      results suggest that DIE lesions do not originate from the rectovaginal septum.

PMID- 12186985
TI  - Nuchal translucency thickness and fetal cardiac flow velocity in normal fetuses
      at 11-13 weeks of gestation.
AB  - OBJECTIVE: To investigate the relationship between nuchal translucency thickness
      and cardiac flow velocity in normal fetuses at 11-13 weeks of gestation. SUBJECTS
      AND METHODS: Eighteen normal pregnancies were prospectively studied with
      transvaginal sonography and pulsed and color Doppler ultrasound. Flow velocities
      at the fetal atrioventricular valves (mitral and tricuspid valve) and outflow
      tract levels (ascending aorta and pulmonary artery), and at the descending aorta
      were recorded. Nuchal translucency thickness was also measured. RESULTS: Mitral
      peak velocity during early diastolic filling correlated with gestational age.
      Mitral peak velocities during early diastolic filling and atrial contraction,
      tricuspid peak velocity during early diastolic filling, ascending aorta peak
      velocity, and pulmonary artery peak velocity correlated well with nuchal
      translucency thickness. There was an inverse correlation between umbilical artery
      pulsatility index and gestational age. CONCLUSIONS: These results suggest that
      the increase of nuchal translucency thickness in normal fetuses at 11-13 weeks of
      gestation may be the consequence of changes in fetal cardiac functions.

PMID- 12186986
TI  - Comparison of total laparoscopic hysterectomy and laparoscopically assisted
      vaginal hysterectomy.
AB  - We compare the surgical results of 60 women undergoing laparoscopically assisted
      vaginal hysterectomy (LAVH) and 41 having total laparoscopic hysterectomy (TLH)
      under the indications of uterine fibroids or adenomyosis. With similar specimen
      weight, TLH required longer surgery duration (140.4 vs. 115.1 min; p < 0.05) than
      LAVH. Among women with uteri weighing <or=200 g, TLH resulted in relatively
      smaller blood loss with comparable operating time (115.6 vs. 116.0 min for LAVH;
      p > 0.05) although the TLH group had a significantly higher rate of previous
      abdominal surgery (57.7 vs. 20%; p < 0.05). There were no significant differences
      between the two groups with respect to the mean cost, length of hospital stay and
      rate of various complications (p > 0.05). As for sexual symptoms, dyspareunia
      decreased significantly post-operatively in the LAVH group (p < 0.05), but not in
      the TLH group. A significant reduction in the frequency of orgasms after surgery
      was detected in both groups (p < 0.05). In conclusion, LAVH has advantages over
      TLH with reduced operating time. Although it is a technical challenge, TLH can be
      effectively performed within reasonable time limits in selected cases. The
      effects on sexual function, following either LAVH or TLH, are found to be
      similar.

PMID- 12186987
TI  - A prospective comparative study on IVF outcomes with either purified FSH or human
      menopausal gonadotrophin in downregulated normogonadotrophic women.
AB  - OBJECTIVE: In compare the use of purified follicle-stimulating hormone with that
      of a preparation containing follicle-stimulating hormone and luteinizing hormone
      in infertile females undergoing IVF. DESIGN: Open-labelled prospective controlled
      single-center study. SETTING: Nile Badrawy IVF unit. PARTICIPANTS: 153 infertile
      females undergoing their first cycle of IVF divided into 2 groups. INTERVENTIONS:
      Ovarian stimulation was done with either highly purified FSH for group 1 (n = 75)
      or human menopausal gonadotrophin group 2 (n = 78) after pituitary
      desensitization commenced in the midluteal phase of the preceding cycle.
      Monitoring was performed by ultrasound transvaginal oocyte retrieval followed by
      IVF and transfer of three embryos. OUTCOMES: Number of oocytes >18 mm at day of
      hCG, fertilization rate, embryo transfer rate, clinical pregnancy rate and
      incidence of ovarian hyperstimulation syndrome. RESULTS: The response to ovarian
      hyperstimulation was similar in both groups. The number of follicles >18 mm
      achieved at day of hCG was 12.3 +/- 0.9 (mean +/- SEM) following stimulation with
      38.3 +/- 0.9 ampoules of Fostimon The Menogon-treated group needed 39.1 +/- 0.8
      ampoules to produce 11.6 +/- 0.7 follicles. Fertilization rate (2PN/cell) was
      58.6 vs. 64.2% in the Fostimon and Menogon group, respectively (p > 0.05). The
      number of embryos transferred per woman was 3.1 +/- 0.1 in the Fostimon group and
      3.6 +/- 0.1 in the Menogon group. The pregnancy rate per woman was 33.3 vs. 25.6%
      in the Fostimon- and Menogon-treated groups, respectively (p > 0.05). Miscarriage
      rate was 16 vs 20%, respectively. However, the incidence of multiple pregnancies
      was significantly higher in the Fostimon-treated group (32%) vs. 10% only in the
      Menogon-treated group (p < 0.01). CONCLUSION: Purified FSH yields similar
      clinical outcome to hMG in terms of oocytes retrieved and clinical pregnancies in
      a standard IVF regimen.

PMID- 12186989
TI  - Magnetic resonance imaging diagnosis of a deep soft tissue leiomyoma under the
      rectus muscle.
AB  - Leiomyomas of the deep soft tissue are extremely rare. We report a case of a deep
      soft tissue leiomyoma that was difficult to differentiate from a uterine
      leiomyoma. A 48-year-old woman was diagnosed with a uterine leiomyoma, but
      surgical and pathological findings revealed a deep soft tissue leiomyoma and
      normal uterus.

PMID- 12186990
TI  - Repair of vaginal prolapse following penoscrotal flap vaginoplasty in a male-to
      female transsexual.
AB  - Penis and testicle amputation, vaginoplasty, and clitoroplasty are procedures
      that help male-to-female transsexuals to accept their body and to increase
      psychosocial well-being. We describe a successful correction of prolapse of the
      neovagina with abdominovaginal sacropexy in a male-to-female transsexual who had
      undergone penoscrotal flap vaginoplasty. Although the reasons for a neovaginal
      prolapse are not completely known, in our case vaginal sacropexy was successful,
      with good functional and cosmetic results.

PMID- 12186988
TI  - The expression of apoptosis-related proteins Bcl-2 and Ki67 in endometrium of
      ovulatory menstrual cycles.
AB  - BACKGROUND: During the menstrual cycle, a rapid sequence of proliferation,
      differentiation and cell death occurs in the human endometrium. Mechanisms
      involved in cell proliferation have been studied extensively. Apoptosis has
      recently been recognized to be a physiologic phenomenon. The aim of this study
      was to investigate the mechanisms involved in hormone-dependent tissue remodeling
      by measuring Bcl-2, an apoptosis inhibitor, and Ki67, a proliferation marker, as
      expressed in normal human endometrium. METHODS: Paraffin-embedded endometrial
      sections of 30 uteri were immunostained for Bcl-2 and Ki67; expression was scored
      in cavitary epithelium, functional and basal glandular epithelial and stromal
      cells of the endometrium. RESULTS: Bcl-2 expression increased in the
      proliferative phases and decreased significantly in the secretory phases,
      especially in glandular epithelial cells (131 +/- 45 for functional laminal cells
      and 227 +/- 68 for basal laminal cells to 0). Ki67 expression showed the same
      cyclic pattern with a later onset (145 +/- 63 for functional laminal cells and 13
      +/- 8 for basal laminal cells to 0). CONCLUSION: Bcl-2 promotes cell survival by
      preventing apoptosis. Proliferation is the result of increasing estradiol
      concentration, high estrogen receptor expression and growth hormones and high Bcl
      2 and Ki67 expression. After the onset of progesterone production, Bcl-2 levels
      decrease and Ki67 levels and androgen receptor expression in stromal cells
      disappear resulting in cell disintegration and menstruation. Persistent Bcl-2
      expression, like we saw in basal laminal stromal and epithelial cells, accounts
      for the privilege of escaping from apoptosis-inducing signals. This allows
      reconstruction of the functional endometrium from its preserved basal layer after
      menstruation.

PMID- 12186991
TI  - Antepartum assessment of fetal cystic lymphangioma by magnetic resonance imaging.
AB  - Few reports of fetal cystic lymphangioma have described assessment in utero by
      magnetic resonance imaging (MRI). We evaluated a fetus with cystic lymphangioma
      by this method. Complementing the characteristic features of cystic lymphangioma
      in ultrasonographic images, prenatal MRI provided a detailed view of anatomic
      relationships of cysts to surrounding tissues in this case. This anatomic
      evaluation facilitated planning of perinatal management and choice of manner of
      delivery. We found MRI very helpful in antepartum assessment of fetal cystic
      lymphangioma.

PMID- 12186992
TI  - A case of postpartum cerebellar infarction with hemolysis, elevated liver
      enzymes, low platelets (HELLP) syndrome.
AB  - Cerebellar infarction has been described rarely during pregnancy, and there has
      been no case report of cerebellar infarction with hemolysis, elevated liver
      enzymes, low platelets (HELLP) syndrome. A 39-year-old Japanese primipara had
      postpartum HELLP syndrome soon after cesarean section at term. Several hours
      later, she developed cerebellar infarction which was fatal. HELLP syndrome may
      have contributed to the development of cerebellar infarction in the case.

PMID- 12186993
TI  - Hyperreactio luteinalis associated with severe twin-to-twin transfusion syndrome.
AB  - Twin-to-twin transfusion syndrome (TTTS) is a severe complication of
      monochorionic twin pregnancies, with high perinatal loss and significant
      morbidity. The etiology of this syndrome remains unclear. Hyperreactio luteinalis
      is a rare benign condition characterized by maternal ovarian enlargement due to
      theca lutein cysts. We present 4 cases of hyperreactio luteinalis associated with
      severe TTTS. We detected maternal ovarian enlargement by prenatal ultrasonography
      in 2 cases, at the cesarean section in 1 case, and postpartum in 1 case. Three
      cases showed hydrops fetalis and all cases showed congestive cardiac failure.
      Serial amnioreduction was performed in all cases, and regression of hydrops
      fetalis and maternal ovarian enlargement occurred in 1 case. These cases suggest
      that the pathophysiology of TTTS is closely related to the etiology of
      hyperreactio luteinalis.

PMID- 12186994
TI  - Does the neurologist contribute to the care of patients with chronic back pain?
AB  - OBJECTIVE: To review the disposition and outcome of patients with back pain seen
      in a neurology clinic, and determine the value of the neurologist's input.
      BACKGROUND: Back pain is a common cause of referral to the neurology clinic, but
      it is not clear how much the neurologist contributes to the care of such
      patients. DESIGN/METHODS: We reviewed all new patients and new consultations seen
      for the following reasons: low back pain; 'sciatica'; 'back and leg pain', and
      'spinal stenosis'. Patients were evaluated by a single attending neurologist at a
      general neurology clinic over a 2-year period (January 1997 through December
      1998). RESULTS: During the 2-year period, there were 97 patients seen for the
      above reasons. The chief complaint was low back pain alone in 73, while it was
      combined with another symptom in 24 (leg pain in 18, buttock or hip pain in 6).
      Thirty-three patients were self-referred, 56 were referred by a healthcare
      professional, 3 were referred by attorneys, and the referral source was unclear
      in 5. Median age was (range 25-90) years. Forty-eight were males. Based on the
      clinical data (history and examination), clinical diagnoses were radiculopathy in
      28, myelopathy in 2, uncomplicated spondylosis in 27, and other non-neurologic
      conditions in 45. Tests performed after the visit included X-rays in 31, CT in 1,
      MRI in 16, and EMG in 17. 'Final' diagnoses were radiculopathy in 29 patients,
      myelopathy in 2 (total neurologic n = 30), uncomplicated spondylosis in 27, and
      other non-neurologic diagnoses in 41 (total non-neurologic n = 67). The non
      neurologic diagnoses included periarticular pain, bursitis, muscle strain, soft
      tissue injury, and vertebral compression fractures. Final dispositions in the non
      neurologic group (n = 67) were: nonsteroidal anti-inflammatories (NSAIDs) in 34
      patients; analgesics or muscle relaxants in 37; physical therapy for 19, and none
      (including rest and observation) for 22. Four patients were referred for epidural
      blocks. (Many patients had more than one final disposition.) Final dispositions
      in the neurologic group (n = 39) were: physical therapy (n = 9); NSAIDs (n = 12);
      analgesics or muscle relaxants (n = 12), and epidural blocks (n = 3). Three
      patients were referred for surgery, but only 1 had an operation. CONCLUSIONS: Of
      patients with back pain and related symptoms seen in a neurology clinic, about
      two thirds have non-neurologic conditions. These patients are usually treated
      symptomatically with medications, rest, and physical therapy, all of which could
      be managed by primary care physicians. In the neurologic group, the vast majority
      is treated in the same way as the non-neurologic group. When more specific
      measures are needed, such as surgery or pain management procedures (e.g.,
      epidural blocks), then the patients could be evaluated directly by the proper
      specialist (pain management or spine surgery) rather than the neurologist. The
      neurologist's input does not significantly affect the diagnosis or the
      management, so that the neurologist appears to have no useful role in the
      management of such patients.

PMID- 12186996
TI  - Comparison of different methods evaluating the functional and structural
      abnormalities in hypertension.
AB  - Functional and morphological abnormalities due to hypertension could be detected
      in neurologically symptom-free patients by CT, MRI, transcranial Doppler
      ultrasound, PET and SPECT. Neuropsychological tests also provide useful
      information. Single or combined application of these techniques reveals different
      aspects of parenchymal or vascular impairment in hypertension. The advantages and
      disadvantages of the different imaging techniques are reviewed and compared. The
      relatively simple, non-invasive transcranial Doppler (alone or combined with
      neuropsychological observations) could be recommended for screening and follow-up
      of hypertensive patients and seems to be a promising ancillary tool for
      evaluation of efficacy of antihypertensive therapy, but cannot replace the
      prospective controlled trials with hard endpoints.

PMID- 12186995
TI  - Hypometabolism and interictal spikes during positron emission tomography scanning
      in temporal lobe epilepsy.
AB  - To study the influence of interictal spikes on (18)F-fluorodeoxyglucose positron
      emission tomography (FDG-PET), EEG monitoring was performed during PET scanning
      in 21 patients with temporal lobe epilepsy. Asymmetry indices were calculated in
      the polar, mesial, anterior-lateral, mid-lateral and posterior-lateral temporal
      region of interests of FDG-PET (PET-AI). 70.7% of spikes were recorded with their
      maximum at the anterior temporal region (F(7), F(8), FT(9), FT(10)), 29.3% at mid
      temporal (T(7), T(8)), and none at posterior temporal region (P(7), P(8)).
      Regardless of the side of epileptic focus, right-left difference of the total
      spikes had a significant negative correlation with right/left PET-AIs of the
      anterior-lateral temporal region (Spearman's rho = -0.565, p = 0.009), polar (rho
      = -0.500, p = 0.021) and whole temporal region (rho = -0.480, p = 0.028). FDG-PET
      hypometabolism may reflect not only a permanent functional deficit but also a
      transient regional cerebral dysfunction related to the occurrence of interictal
      spikes.

PMID- 12186997
TI  - Study of psychopathology in patients with chronic non-lesional epilepsy: a
      Minnesota multiphasic personality inventory profile controlled study.
AB  - OBJECTIVE: Psychiatric morbidity and psychopathology have been widely assessed in
      patients with epilepsy. However, the issue of whether people with epilepsy are at
      increased risk for psychopathology remains highly controversial. These disorders
      are not evaluated in a systematic manner in patients with non-lesional epilepsy,
      so they could be underestimated. The objective is to evaluate personality
      disorders in patients with non-lesional epilepsy. METHODS: In this study, we
      investigated the presence of personality disorders in 63 patients with chronic
      non-lesional (idiopathic and cryptogenic) epilepsy and in 40 unrelated and
      randomly selected controls by means of Minnesota Multiphasic Personality
      Inventory (MMPI) and DSM-IV criteria for the different personality disorders.
      RESULTS: The overall scores were significantly higher in the patients in the
      subscales of schizophrenia, depression, hysteria, mania, paranoia, psychasthenia
      and psychopathic deviate. However, the differences in the proportion of patients
      with clinically significant scores occurred only for schizophrenia (57 vs. 20%),
      depression (55 vs. 15%), psychasthenia (28 vs. 10%) and paranoia (14 vs. 0%).
      According to DSM-IV criteria, only 11 patients met the criteria of schizotypal
      personality. We found excellent concordance for paranoid personality and
      depression between the two instruments of diagnosis. However, we did not find
      cases with either antisocial or avoidant personality. We also found a significant
      link between poor control of epilepsy and high scores in both paranoia and
      psychopathic deviate. CONCLUSIONS: In comparison with the DSM-IV criteria for
      such personality disorders, the MMPI was oversensitive in detecting schizotypal
      features. However, the MMPI correctly classified the remaining personality
      disorders, especially depression and paranoid personality. On the basis of these
      results, we conclude that psychopathology is overrepresented in patients with
      chronic non-lesional epilepsy and that, in determined variables, this is due to
      the severity of the condition rather than to the type and duration of epilepsy.
      The approach to patients with chronic epilepsy should include neurobehavioural
      scales.

PMID- 12186998
TI  - Kinesthetic alexia due to left parietal lobe lesions.
AB  - To investigate the neuropsychological mechanisms of kinesthetic alexia, we asked
      7 patients who showed kinesthetic alexia with preserved visual reading after
      damage to the left parietal region to perform tasks consisting of kinesthetic
      written reproduction (writing down the same letter as the kinesthetic stimulus),
      kinesthetic reading aloud, visual written reproduction (copying letters), and
      visual reading aloud of hiragana (Japanese phonograms). We compared the
      performance in these tasks and the lesion sites in each patient. The results
      suggested that deficits in any one of the following functions might cause
      kinesthetic alexia: (1) the retrieval of kinesthetic images (motor engrams) of
      characters from kinesthetic stimuli, (2) kinesthetic images themselves, (3)
      access to cross-modal association from kinesthetic images, and (4) cross-modal
      association itself (retrieval of auditory and visual images from kinesthetic
      images of characters). Each of these factors seemed to be related to different
      lesion sites in the left parietal lobe.

PMID- 12186999
TI  - Genotype correlation with fine motor symptoms in patients with Wilson's disease.
AB  - Wilson's disease, an autosomal recessive disorder of copper metabolism, is caused
      by about 200 different mutations of the ATP7B gene. Using a genotype-phenotype
      correlation, 36 patients were examined to see whether the disorder of the
      automatic handwriting movement depends on the genotype. The findings of this
      study indicated that no such link exists. Neither the profile of the impairment
      of the fine motor parameters nor the severity and frequency of pathological
      findings were different among the three genotype groups (homozygous for H1069Q,
      compound homozygous for H1069Q and other mutations). By contrast, fine motor
      disorders were found to correlate with the clinical symptoms recorded when
      therapy began. The pathophysiology of the basal ganglia and the cerebellar loop
      therefore cannot be directly attributed to the genotype of the mutation in the
      ATP7B gene.

PMID- 12187000
TI  - Alterations of quantitative EEG and mini-mental state examination in interferon
      alpha-treated hepatitis C.
AB  - We have recently observed a diffuse slowing of brain waves using serial
      quantitative electroencephalographic (qEEG) examinations in interferon (IFN)
      alpha-treated chronic hepatitis C patients. However, it remains unclear how this
      alteration could be assessed. We evaluated the correlation between the qEEG
      changes and three tests of mental status, including the Mini-Mental State
      Examination (MMSE), in such patients. This is the first study to undertake a
      clinical evaluation of the adverse effects on brain function due to IFN. We
      undertook blind, prospective and serial qEEG examinations on 56 chronic hepatitis
      C patients at three independent hospitals. IFN-alpha was administered
      intramuscularly at a dose of 9 x 10(6) IU daily for the first 4 weeks and then 3
      times/week for the next 20 weeks. Serial EEGs were obtained before, at 2 and 4
      weeks of treatment, and after the IFN-alpha treatment. The absolute power values
      of each frequency band in each patient at different stages of treatment were
      recorded by qEEG. Each patient was assessed by the MMSE, Hamilton Rating Scale
      for Depression (HSD), and Hamilton Rating Scale for Anxiety (HSA). We
      statistically evaluated the correlations between the changes in power values and
      alterations of scores on the mental status tests during IFN-alpha treatment. The
      decreased scores observed on the MMSE ranged from 2 to 5 points at both 2 and 4
      weeks of IFN-alpha treatment. There were no significant differences in age
      distribution for each decreased score on the MMSE. As the alteration in MMSE
      score during IFN treatment increased, the alteration in absolute power values for
      the slow waves during IFN treatment increased significantly, while that for the
      alpha 2 and fast waves during treatment decreased significantly. However, the
      changes in the HDS and HSA revealed no significant correlations. The alteration
      of the qEEG was reversible after the treatment. MMSE scores represent one
      screening method for the clinical assessment of IFN-alpha-induced alterations of
      brain function.

PMID- 12187001
TI  - Sleep laboratory diagnosis of restless legs syndrome.
AB  - Polysomnographic recordings and the Suggested Immobilization Test (SIT) are
      frequently used to support the clinical diagnosis of restless legs syndrome
      (RLS). The present study evaluated the discriminant power of 5 different
      parameters: (1) index of periodic leg movements during sleep (PLMS), (2) index of
      PLMS with an associated microarousal (PLMS-arousal), (3) index of PLM during
      nocturnal wakefulness (PLMW), (4) SIT PLM index and (5) mean subjective leg
      discomfort score during the SIT (SIT MDS) in 100 patients with idiopathic RLS and
      50 healthy control subjects. Both groups differed significantly on each parameter
      studied. Furthermore, while the SIT PLM, the PLMS and the PLMS-arousal indices
      revealed a poor ability to discriminate patients from controls, the PLMW index
      and the MDS both showed high sensitivity (87 +/- 7 and 82 +/- 8, respectively)
      and specificity (80 +/- 11 and 84 +/- 10, respectively) for diagnosing RLS. The
      combination of these 2 parameters correctly classified 88% of all subjects with a
      sensitivity of 82% and a specificity of 100%.

PMID- 12187002
TI  - Roles of gender, age at onset and environmental risk in the frequency of CYP2D6
      deficient alleles in patients with Parkinson's disease.

PMID- 12187003
TI  - The effect of combined therapy with immunoadsorption and high-dose intravenous
      methylprednisolone on myasthenia gravis.

PMID- 12187005
TI  - Diffusion-weighted magnetic resonance imaging of porphyric encephalopathy: a case
      report.

PMID- 12187004
TI  - High anti-GM1 and anti-GD1a IgG antibody titers are detected in Guillain-Barre
      syndrome but not in chronic inflammatory demyelinating polyneuropathy.

PMID- 12187006
TI  - Acute cerebellar ataxia with an MRI abnormality: a sequential imaging study.

PMID- 12187007
TI  - Bilateral basal ganglia infarctions in a patient with Streptococcus pneumoniae
      meningitis.

PMID- 12187008
TI  - The heart of the matter.

PMID- 12187009
TI  - Electrocardiographic changes in patients with acute stroke: a systematic review.
AB  - Repolarization and ischemic-like electrocardiographic (ECG) changes observed
      during acute phase of stroke may cause diagnostic and management dilemmas for the
      clinician. In this systematic review, we have compiled all information available
      in the literature on the prevalence of these ECG changes and QT prolongation
      during the acute phase of stroke and their coexistence with other abnormal
      cardiac findings. Abnormalities, such as ischemic-like ECG changes and/or QT
      prolongation, were found in 76% (95% CI 73-90) of patients with subarachnoid
      hemorrhage, irrespective of whether they had preexisting heart disease or not.
      Such ECG changes were present in more than 90% of unselected patients with
      ischemic stroke and intracerebral hemorrhage, but the prevalence was much lower
      after exclusion of patients with preexisting heart disease. Compared with other
      abnormal cardiac findings (cardiac wall motion abnormality detected by
      echocardiography, elevated levels of biochemical markers of myocardial injury,
      autopsy findings, thallium scintigraphy), these ECG changes were characterized by
      a high sensitivity but a very low specificity. Thus, in patients with
      subarachnoid hemorrhage, repolarization and ischemic-like ECG changes are mainly
      direct consequences of the cerebral condition and their absence essentially rules
      out cardiac abnormalities. In patients with ischemic stroke and intracerebral
      hemorrhage, these ECG abnormalities (and QT prolongation) most often represent
      preexisting coronary artery disease. The specificity of ECG changes to diagnose
      acute myocardial infarction is low in the acute phase of stroke.

PMID- 12187010
TI  - Determinants of plasminogen activator inhibitor-1 in South Asians with ischaemic
      stroke.
AB  - To investigate the relationship of circulating plasminogen activator inhibitor-1
      (PAI-1) levels with features of insulin resistance and genotype at a single
      nucleotide insertion/deletion (4G/5G) polymorphism in the promoter region of the
      PAI-1 gene in 101 South Asian ischaemic stroke patients and 102 symptom-free
      reference subjects. The allele frequencies were 4G-0.51, 5G-0.49 and 4G-0.61, 5G
      0.39 in patients and reference subjects, respectively. There was a significant
      association between PAI-1 promoter genotype and PAI-1 antigen levels in patients.
      Regression analysis with significant correlates in the model demonstrated age,
      gender and triglycerides in patients and fasting insulin and HDL cholesterol in
      reference subjects as independent predictors of PAI-1 antigen.

PMID- 12187011
TI  - Symptom spread to contiguous body parts as a presentation of cerebral ischemia.
AB  - BACKGROUND: Ischemic stroke commonly presents with sudden onset of focal deficit
      that is maximal at onset. Symptom onset marked by the spread of symptoms to
      contiguous body parts may suggest migraine, seizure or cerebral amyloid
      angiopathy (CAA) that is mimicking ischemic symptoms. OBJECTIVE: To assess (1) if
      the spread of symptoms to contiguous body parts is an uncommon presentation of
      ischemic stroke and transient ischemic attack (TIA) and (2) if patients
      presenting with this symptom complex frequently have migraine, seizure or CAA
      mimicking stroke or TIA. METHODS: 110 consecutive patients presenting with stroke
      like symptoms were prospectively evaluated for symptoms at onset, abnormalities
      on cerebral imaging, risk factors for stroke, discharge diagnosis, and
      development of subsequent TIA/stroke, migraine, seizure, or cerebral hemorrhage
      during follow-up. RESULTS: Of patients able to give a history of symptoms at
      onset, 23% described symptoms spreading to contiguous body parts. None had a
      history of migraine or seizure. None had clinical course or imaging features
      typical of CAA. During follow-up, 1 was diagnosed with migrainous stroke and none
      had suffered seizure or intracranial hemorrhage. CONCLUSIONS: The spread of
      symptoms to contiguous body parts is not uncommon at the onset of ischemic
      TIA/stroke. In our series, migrainous stroke was much less common and none had
      evidence of seizure or CAA.

PMID- 12187012
TI  - Insomnia in ischemic stroke patients.
AB  - This is the first study that focuses on insomnia in stroke patients. A subgroup
      of 277 patients from a consecutive series of 486 stroke patients aged 55-85 years
      was subjected to a comprehensive psychiatric evaluation 3-4 months after ischemic
      stroke. Of 277 patients, 56.7% reported any insomnia complaint and 37.5%
      fulfilled the DSM-IV criteria of insomnia. In 38.6%, insomnia complaint/insomnia
      had already been present prior to the stroke and in 18.1%, it was a consequence
      of the stroke. Independent correlates of any insomnia complaint/insomnia were
      anxiety (Zung Anxiety Scale) and the use of psychotropic drug. Independent
      correlates of poststroke-onset insomnia complaint/insomnia were disability after
      stroke (Barthel Index), dementia, anxiety and use of psychotropic drug. Insomnia
      should be taken into consideration in treating and rehabilitating stroke
      patients.

PMID- 12187013
TI  - The Venturi effect and cerebrovascular ultrasound.
AB  - BACKGROUND: One of the most frequent diagnostic pitfalls in cerebrovascular
      ultrasound is the evaluation of the vertebrobasilar system in the case of
      vertebral artery (VA) hypoplasia because the diagnostic findings are sometimes
      suggestive of significant pathologies, but may be completely normal as well. The
      Venturi effect is a phenomenon of hydrodynamics which describes a drop in
      hydrostatic pressure along areas of high flow velocities. METHOD: We review the
      physical background of the Venturi effect and describe how it can explain both
      physiological and pathological flow phenomena encountered during cerebrovascular
      ultrasound investigations. We focused on flow phenomena at the vertebrobasilar
      junction by theoretically calculating conditions with different influx angles and
      flow velocities on two-dimensional digital subtraction angiography images. In the
      discussion, we also address other areas of cerebrovascular ultrasound, where the
      Venturi effect is of particular interest. RESULTS AND CONCLUSIONS: The blood flow
      velocity within the VAs and the angle between a hypoplastic VA and the basilar
      artery (BA) are important determinants of the intraluminal pressures of these
      arteries and thus their resistances. In the case of angles below 90 degrees
      between the distal VA and the BA, abnormal extracranial flow profiles may suggest
      downstream VA stenosis or occlusion, whereas in the case of angles above 90
      degrees, a diagnosis of an AV fistula downstream to the V4 segment may be
      assumed. Furthermore, various hemodynamic effects at the site of a stenosis of
      the brain supplying arteries can also be explained by a transstenotic pressure
      drop created by the Venturi effect, particularly the generation of musical
      murmurs. The systolic dip ('systolic deceleration') at the origin of the VA due
      to subclavian artery stenosis is also a consequence of the Venturi effect.

PMID- 12187015
TI  - Longitudinal study of carotid atherosclerosis and white matter hyperintensities:
      the EVA-MRI cohort.
AB  - BACKGROUND AND PURPOSE: White matter hyperintensities (WMHs) are often observed
      on cerebral magnetic resonance imaging (MRI) of elderly individuals.
      Epidemiological studies have shown that age and hypertension are associated with
      WMHs, suggesting a vascular mechanism in WMH pathogenesis. In a population-based
      prospective study, we examined the association of carotid atherosclerosis
      measured at baseline and 4-year follow-up with severity of WMHs assessed at 4
      year follow-up. METHODS: The sample consisted of 640 healthy subjects aged 59-71
      years at entry enrolled in the prospective EVA Study. Systolic and diastolic
      blood pressures were measured at each wave. Ultrasonographic measures of intima
      media thickness (IMT) of the common carotid arteries and plaques were made at
      baseline and at 4-year follow-up examination. An MRI examination was performed at
      4-year follow-up. The presence and severity of WMHs were evaluated by a single
      radiologist. RESULTS: After adjusting for age, gender, and hypertension, the
      presence of carotid plaques at baseline was significantly associated with the
      presence of severe WMHs 4 years later [odds ratio (OR) = 1.70; 95% confidence
      interval (CI): 1.05-2.74]. The association was stronger in men than in women. A
      0.1-mm increase of baseline IMT was associated with an increased risk of severe
      WMHs in both sexes (adjusted OR = 1.17; 95% CI: 0.96-1.41), but the association
      was not significant (p = 0.12). Cross-sectional relationships between carotid
      plaques and severe WMHs at 4-year follow-up showed that the risk of having severe
      WMHs was stronger in the group of subjects who had already plaques at study entry
      compared to the group of subjects whose plaques occurred during 4-year follow-up.
      CONCLUSION: This study confirmed an association between carotid atherosclerosis
      and WMHs independently of age and hypertension. It also suggested that the older
      the carotid plaques, the higher the risk of having severe WMHs.

PMID- 12187014
TI  - Effects of the ultrasound contrast-enhancing agent Levovist on the detection of
      intracranial arteries and stenoses in chinese by transcranial Doppler ultrasound.
AB  - Proper assessment of intracranial arteries by transcranial Doppler sonography
      (TCD) in patients with intracranial stenoses is occasionally made difficult by an
      insufficient temporal bone window, an unfavourable insonation angle, or low flow
      velocity or volume. This condition is frequently found in Chinese. In these
      cases, echocontrast could be helpful. We investigated 48 temporal windows of 24
      acute Chinese stroke patients with insufficient native transtemporal insonation
      conditions before and after the application of the echo enhancer Levovist
      (galactose/palmitic acid) by an injection pump. We classified the signal quality
      from four segments of the main intracranial arteries: anterior cerebral artery
      (A1), main stem of the middle cerebral artery (MCA, M1), intracranial segment of
      the carotid artery (C1), and posterior cerebral artery (P1). The signal quality
      was classified as follows: 0 = no signal, 1 = poor, envelope curve does not
      follow spectrum, 2 = adequate, envelope curve follows spectrum. As compared to
      the pre-contrast scans, echocontrast allowed for more segments to be evaluated by
      pulsed Doppler sonography. Before Levovist, only 12% of the segments could be
      detected, after Levovist 63%. For all arteries, signal quality was better after
      Levovist, p between 0.0180 and 0.0003. In 3 patients, MCA stenoses with peak
      systolic Doppler flow velocities above 160 cm/s were found only after Levovist.
      In patients with poor pre-contrast detection, echocontrast-enhanced TCD allows
      for more arterial segments to be insonated and for the detection of stenoses
      unnoted during the non-enhanced investigation.

PMID- 12187016
TI  - Burden of acute stroke and hospital resources in the Campania region of Italy.
AB  - We examined all the official hospital records referring to admissions for acute
      stroke (AS) (DRG 14) from January 1 to December 31, 1996 in Campania (Italy), a
      large region with 10% of the Italian population. Related healthcare burden and
      available resources were evaluated. During the study period, a total of 9,003
      discharges were reported. We counted 11 neurological care units (NCU) committed
      to emergency in the region, with 230 hospital beds. The 4,890 admissions in NCU
      represented 54.3% of the total AS hospitalizations per year. A large number of
      strokes (45.7%) had no access to specialist assistance and were hospitalized
      mainly in general wards with a mean hospital stay of 12.7 days, compared with 9.5
      days in NCU (p < 0.01). In our region, the number of hospital beds available for
      neurological emergencies do not meet the demand.

PMID- 12187017
TI  - Sexual functioning in Chinese stroke patients with mild or no disability.
AB  - This study was conducted to assess the effects of stroke on sexual functioning of
      patients with mild or no disability and to explore the associations of clinical
      and psychosocial factors with post-stroke changes in sexual functions.
      Consecutive stable Chinese patients were invited to complete a self-administered
      questionnaire concerning their pre- and post-stroke sexual functions and habits.
      Results from this cohort of 63 men and 43 women revealed a post-stroke decrease
      in libido, coital frequency, sexual arousal, orgasm and sexual satisfaction in
      54.3%, 43.8%, 25.0% (women) to 51.6% (men), 20.0% (women) to 45.9% (men) and
      28.6% of patients, respectively. Logistic regression indicated unwillingness for
      sex and a belief in an adverse effect of stroke on sexuality as explanatory
      factors for decreased sexual satisfaction. Thus, sexual dysfunctions are common
      in Chinese stroke patients with mild or no disability.

PMID- 12187018
TI  - Noninvasive monitoring of hypertensive breakthrough of cerebral autoregulation in
      a patient with acute ischemic stroke.
AB  - BACKGROUND AND PURPOSE: We describe the first documentation of hypertensive
      breakthrough of cerebral autoregulation in a patient with acute stroke with
      transcranial Doppler sonography. CASE DESCRIPTION: A 55-year-old patient with
      acute left hemispheric stroke was treated with moderate hypothermia. He died of
      transtentorial herniation 4 days after admission. Static cerebral autoregulation
      (sCA) of the unaffected hemisphere was evaluated 6 times during this period and
      always found to be intact. A bolus application of epinephrine resulted in a
      hypertensive episode (mean arterial pressure (MAP) 135 mm Hg); hypertensive
      breakthrough of cerebral autoregulation was evident when MAP exceeded
      approximately 110 mm Hg. Interestingly, no such breakthrough was evident during
      testing of sCA, even when MAP reached 120 mm Hg. CONCLUSIONS: Our observation
      suggests that (1) the pace of the MAP increase is crucial for the occurrence of a
      hypertensive breakthrough of the cerebral autoregulation and (2) the disturbance
      of cerebral autoregulation is potentially longer as previously assumed.

PMID- 12187019
TI  - Cerebral occlusive artery disease in Noonan syndrome.
AB  - Noonan syndrome is an autosomal-dominant inherited syndrome with variable
      expression of multiple malformations including cardiovascular and craniofacial
      anomalies. While cerebrovascular insults due to cardiogenic emboli, coagulation
      abnormalities or cerebrovascular malformations have been documented before,
      intracerebral occlusive artery disease is not well recognized as a cause of
      stroke in this syndrome. A 6-year-old girl with Noonan syndrome presented with
      repetitive transient ischemic attacks consisting of dysphasia and right-sided
      central facial and arm weakness. Neuroimaging showed acute ischemic lesions in
      the left putamen and caudate nucleus. Multiple intracranial stenoses were found
      during transcranial Doppler examination and MR angiography. Although hypertrophic
      cardiomyopathy was documented by transesophageal echocardiography, a
      cardioembolic origin of the ischemic attacks was unlikely in this case. The
      symptoms resolved and did not recur after antiplatelet and anticoagulant therapy
      was initiated. Stenoses of intracranial cerebral arteries should be considered
      among the causes of stroke in young patients with Noonan syndrome.

PMID- 12187020
TI  - Pure or predominantly sensory transient ischemic attacks associated with
      posterior cerebral artery stenosis.
AB  - Pure or predominantly sensory transient ischemic attacks (ps-TIAs) are uncommon,
      and underlying vascular abnormalities have rarely been described. The author
      reports 5 patients with TIAs which were of short duration, stereotypical and
      purely or predominantly sensory in nature. Brain MRI did not reveal any lesions,
      while angiography demonstrated focal stenoses in the proximal portion of the
      posterior cerebral artery (PCA). It is concluded that ps-TIAs strongly suggest
      the presence of PCA disease. Repeated compromise of small vessels supplying the
      posterior-lateral part of the thalamus seems to be the pathogenic mechanism.

PMID- 12187021
TI  - Follow-up examinations by transcranial Doppler ultrasound in primary angiitis of
      the central nervous system.
AB  - BACKGROUND: Primary angiitis of the central nervous system (PACNS) is a rare
      disease. The definite diagnosis is made upon proof of mononuclear inflammation of
      the vessel wall on brain biopsy. The diagnosis can also be established on
      clinical grounds, typical findings on intra-arterial angiography and other
      investigatory grounds excluding other diseases. Therapy comprises an aggressive
      immunosuppressive approach. Close monitoring of the patients is mandatory.
      Transcranial Doppler ultrasound (TCD) has not yet been used to follow up the
      vasculitic lesions in PACNS. CASE: We report on a 32-year-old female with massive
      cerebral infarctions secondary to multiple large-vessel stenoses because of
      probable PACNS. The patient was followed closely by means of TCD. During therapy
      the cerebral blood flow velocities normalized as displayed by TCD. Clinical
      improvement followed several days after normalization of cerebral blood flow.
      CONCLUSIONS: TCD is a valuable noninvasive bedside tool to monitor cerebral blood
      flow velocities and therapy response in patients with cerebral vasculitis, if
      large arteries are involved.

PMID- 12187022
TI  - Cytogenetic and molecular genetic aspects of essential thrombocythemia.
AB  - Essential thrombocythemia (ET) is a chronic myeloid disorder that is
      characterized by thrombocytosis, thrombohemorrhagic and vasomotor symptoms, a
      long median survival, and a low risk of transformation to leukemia. ET can be
      difficult to distinguish from secondary (reactive) thrombocytosis, and the
      diagnosis of ET can only be made after the exclusion of other marrow disorders
      with similar features. Although ET has been assumed to be a clonal process,
      recent studies have suggested that a substantial number of cases classified as ET
      may actually not be clonal, and nonclonality may be associated with a lower risk
      of thrombosis. The lack of a characteristic cytogenetic marker for ET confounds
      analyses of clonality and offers no insight into disease pathogenesis. There is
      controversy over the proper classification of thrombocytosis associated with the
      pathological BCR-ABL gene rearrangement; such cases are not clearly
      distinguishable from chronic myelogenous leukemia (CML) and should be
      provisionally classified as CML. New insights are emerging into the role of the
      megakaryocytopoiesis regulator thrombopoietin (TPO) and its receptor, c-Mpl, in
      ET and related disorders, but TPO-Mpl dynamics appear to be complex. In some
      familial thrombocythemic syndromes, mutations in the 5' untranslated region of
      TPO have recently been described, but these have not yet been observed in
      sporadic ET. In the future, global analysis of gene expression patterns may help
      overcome diagnostic dilemmas, refine disease classification, and lead to an
      improved understanding of the pathogenesis of ET.

PMID- 12187023
TI  - Double-blind prospective randomized comparison of interferon gamma-1b versus
      placebo after autologous stem cell transplantation.
AB  - Thirty-eight patients, including 14 with Hodgkin's disease, 9 with non-Hodgkin's
      lymphomas, 4 with multiple myeloma and 11 with solid tumors, were enrolled in our
      study. Between March 1995 and March 1997, 24 of these patients had been
      autografted with peripheral blood, and 14 had received peripheral blood
      autografts plus bone marrow. The study was a double-blind, prospectively
      randomized comparison of interferon gamma-1b (IFN-gamma), given subcutaneously at
      a dose of 50 microg/m(2) daily for 30 days to 18 of the 38 patients, vs. placebo
      (20 of 38). Administration started after 2 consecutive days of >0.5 x 10(9)
      neutrophils/l following autologous stem cell transplantation. At a mean follow-up
      time of 536 +/- 269 days, disease-free survival (DFS) for the IFN-gamma and
      placebo groups was 728 vs. 510 days, respectively (p < 0.0750 by the Generalized
      Wilcoxon/Peto-Prentice test). Overall survival (OS) time for the IFN-gamma and
      placebo groups was 830 vs. 755 days, respectively. Despite the limited number of
      patients included in this comparison, a trend for superior DFS was observed in
      the IFN-gamma-treated group, a finding which merits further study.

PMID- 12187024
TI  - A simplified screening for alpha-thalassemia 1 (SEA type) using a combination of
      a modified osmotic fragility test and a direct PCR on whole blood cell lysates.
AB  - In order to provide a rapid method for identifying alpha-thalassemia 1 in a
      region with massive population and limited resources, we have tested a rapid
      screening strategy. Preliminary screening was done using a modified one tube
      osmotic fragility test (OF test) followed by RBC indices; Hb analysis and
      detection of alpha-thalassemia 1 with the Southeast Asian deletion (SEA type)
      were performed by PCR. One hundred and seventy-five adult Thai subjects were
      studied. Fifty-one of the 175 subjects (29.1%) were positive for a modified OF
      test. They all had significantly lower MCV and MCH but higher RDW-CV values as
      compared to the OF negative group. A successful identification of alpha
      thalassemia 1 deletion using a direct PCR on cell lysates was demonstrated. Among
      the 51 OF-test-positive subjects, 7 were found to be alpha-thalassemia 1
      carriers, 3 of whom were also carriers of Hb E. No alpha-thalassemia 1 was
      detected in the OF-test-negative group. A combination of a modified OF test and a
      direct PCR analysis on whole blood cell lysates would therefore provide an
      effective screening for alpha-thalassemia 1 in the regions where a program of
      prevention and control of the disease remains underserved.

PMID- 12187025
TI  - Evaluation of the incidence of sensorineural hearing loss in beta-thalassemia
      major patients under regular chelation therapy with desferrioxamine.
AB  - With the improved life expectancy of beta-thalassemia major patients, new
      clinical problems, such as hearing loss, must be evaluated. To determine the
      incidence of sensorineural hearing loss and its relationship to desferrioxamine
      (DFO), 128 patients receiving subcutaneous DFO in doses from 21 to 39 mg/kg/day
      were studied. These patients had received their total weekly dose of DFO
      according to two different methods. The first group (QOD group of 52%) had
      received it on an every other day basis. The second group (QD group of 48%) had
      received it on 6 days a week. Otological examinations and pure tone audiometry
      were performed on the patients as they routinely visited Shiraz Cooley's Center,
      to find a possible correlation between the dose and duration of therapy. 56
      patients (44%) in both groups had no evidence of drug-induced auditory
      abnormalities. Of the patients in the QOD group 44.7% had hearing loss in the
      right ear and 41.8% in the left ear at a frequency of 8,000 Hz compared to the QD
      group, 27.8 and 23%, respectively (with p < 0.047 and p < 0.02, respectively). No
      correlation was found between the duration of DFO therapy and sensorineural
      deficit. A significant correlation was found between the dose of drug given at
      each episode of DFO therapy and hearing loss at the frequency of 8,000 Hz, when
      comparing the QOD group with the QD group. Hence, it may be concluded that DFO
      ototoxicity is determined not only by the total amount of the drug given, but
      also by its maximal plasma concentration. Thus we suggest periodical audiologic
      checkups and a low dosage of DFO (below 50 mg/kg/day) given on at least 5-6 days
      a week for the prevention and prompt diagnosis of audiologic complications.

PMID- 12187026
TI  - Evaluation of tumor necrosis factor-alpha and erythropoietin serum levels in B
      cell chronic lymphocytic leukemia patients with anemia.
AB  - Serum levels of tumor necrosis factor-alpha (TNF-alpha) and of erythropoietin
      (Epo) have been evaluated in 100 patients with B-cell chronic lymphocytic
      leukemia (CLL) in order to determine whether these factors could be significant
      in the development of anemia, which was observed in some cases with advanced
      disease. In our series of patients, TNF-alpha serum levels had an inverse
      correlation with hemoglobin levels (r = -0.813). In patients with anemia, the
      serum levels of TNF-alpha were significantly higher (p = 0.022) than in those
      without anemia (186.7 +/- 84.7 vs. 39.8 +/- 20.7 pg/ml). Serum Epo levels were
      also significantly (p = 0.0003) increased in CLL patients with anemia compared to
      those without (134.1 +/- 225.9 vs. 12.3 +/- 4.8 mU/ml). The ratio of
      observed/predicted (O/P) serum Epo was adequate (>0.8) for the degree of anemia
      in 70% of patients with anemia and inadequate in the remaining 30%. In the
      latter, the mean serum TNF-alpha level was significantly higher (p = 0.005) than
      the mean for the anemic cases with an adequate O/P ratio of serum Epo (234.1 vs.
      166.4 pg/ml). These data suggest that although CLL anemia is not characterized by
      inadequate Epo production, in some CLL patients this factor may be correlated. In
      these cases, the levels of TNF-alpha were significantly higher than in other
      anemic cases. Compared to other CLL patients with anemia, these CLL patients
      might better respond to therapy with recombinant human Epo in pharmacological
      doses.

PMID- 12187027
TI  - Iatrogenesis or bad luck? relapse of an LMP1-positive follicular lymphoma after
      immunosuppression for hepatitis-associated aplastic anaemia.
AB  - A 55-year-old man suffered a cutaneous relapse of an LMP1-positive follicular
      lymphoma after treatment with antithymocyte globulin and cyclosporine A (CSA) for
      a hepatitis-associated aplastic anaemia (AA). Rituximab was not effective, so CSA
      was tapered off. Lymphoma masses did not regress but AA relapsed. A second
      remission of both lymphoma and AA was achieved with high-dose cyclophosphamide,
      but the patient died of a bilateral pneumonia. The relationships between
      immunosuppression, viral reactivation and tumour growth are discussed. The use of
      rituximab and lamivudine in immunodepressed patients is also commented.

PMID- 12187028
TI  - Thrombocytosis associated with enzyme replacement therapy in Gaucher disease.
AB  - We describe a patient with an intact spleen and moderately severe symptoms of
      Gaucher disease in whom, after initiation of (low-dose) enzyme replacement
      therapy (ERT), thrombocytosis (720 x 10(9)/l) was documented. Checking the
      International Gaucher Registry database revealed that this patient is the only
      nonsplenectomized patient of more than 1,000 treated patients to experience ERT
      induced thrombocytosis. Platelet counts dropped immediately after the
      discontinuation of ERT.

PMID- 12187029
TI  - Advanced waldenstrom's macroglobulinemia: a case of possible cure after systemic
      chemotherapy, splenic radiation and splenectomy.
AB  - A 41-year-old man with advanced Waldenstrom's macroglobulinemia (WM) associated
      with the hyperviscosity syndrome, massive splenomegaly and with IgM concentration
      of 10 g/dl, was treated in January 1984 with plasmapheresis, systemic
      chemotherapy (M2 protocol) and splenic radiotherapy. He rapidly improved and was
      discharged 1 month later. Fourteen months later he underwent splenectomy since a
      mild splenomegaly persisted though the normalization of bone marrow, peripheral
      blood and electrophoresis with an IgM concentration of 140 mg/dl. However, at
      this time immunofixation and immunoelectrophoresis showed a small IgM-kappa
      monoclonal component. The histological and immunohistochemical analysis showed
      minimal splenic involvement by WM. Two months after splenectomy, immunofixation
      and immunoelectrophoresis showed no monoclonal component. The spleen was the
      probable site of minimal residual disease. The patient was treated with monthly
      chlorambucil and prednisone for 2 years. Subsequently clinical and laboratory
      tests persisted within normal limits. The last control performed in January 2002
      showed that the patient was in good health; bone marrow examination (aspiration,
      biopsy with immunohistochemical analysis) and immunofixation persisted normally.
      This interesting case report, with advanced WM, alive, in good health and without
      signs of disease 18 years from diagnosis, is presented here and the role of
      splenectomy is debated.

PMID- 12187030
TI  - Chronic haemolytic anaemia and glucose-6 phosphate dehydrogenase deficiency. Case
      report and review of the literature.
AB  - Deficiency in glucose-6-phosphate dehydrogenase (G6PD) is the most common
      enzymopathy, and more than 125 different mutations causing G6PD deficiency have
      been identified. Chronic haemolytic anaemia (CHA) associated with G6PD deficiency
      is rare, but there is a cluster of mutations causing CHA between amino acids 361
      428 which are encoded by exon 10 of the G6PD gene. This region is involved in the
      dimer formation of the active G6PD enzyme and therefore plays an important role
      for enzyme stability and activity. Here, we report a 17-year-old patient with
      CHA, who carries a rare G --> A mutation at nucleotide 1160 which causes an R387H
      amino acid substitution. We review the reports of the seven previously described
      patients with this mutation, concluding that G6PD deficiency should be considered
      as a rare differential diagnosis of chronic haemolytic, non-spherocytic anaemia.

PMID- 12187031
TI  - Incidence of nonresponsiveness to epinephrine in platelets from healthy humans.

PMID- 12187032
TI  - Measurement of hemoglobin concentrations using the astrim noninvasive blood
      vessel monitoring apparatus.

PMID- 12187033
TI  - Bone marrow reticulin fibrosis at diagnosis in promyelocytic leukaemia treated
      with all-trans retinoic acid has no adverse prognosis.

PMID- 12187034
TI  - The current diagnosis of superficial bladder cancer must be reconsidered.
AB  - The high recurrence and progression rates in superficial bladder cancer are
      partially related to the deficiencies of the standard conventional diagnostic
      modalities. Therefore, innovative noninvasive and invasive detection devices have
      been studied during the last decade. New diagnostic urine markers are under
      intensive investigation in order to exclude the presence of urothelial cancer,
      but the value of all these tests is still insufficiently validated in diagnosis
      and follow-up. With the introduction of 5-amino-levulinic acid fluorescence
      endoscopy, the efficacy of the detection device has been significantly improved.
      Flat lesions such as carcinoma in situ can be completely detected besides
      exophytic tumors. This is of particular importance because the fate of the
      patient depends to an important extent on these tumor entities. Furthermore,
      first experimental results using imaging devices like optical coherence
      tomography and confocal laser scanning microscopy promise new powerful
      noninvasive tools for 'optical sectioning' of the bladder.

PMID- 12187035
TI  - A new target for urology: aging and renal function.

PMID- 12187036
TI  - Use of pedicle flap from the labia minora for the repair of female urethral
      strictures.
AB  - INTRODUCTION: We present the method of pedicle labial urethroplasty for urethral
      reconstruction in female patients treated for urethral strictures. PATIENTS AND
      METHODS: We performed urethral reconstruction using a pedicle labial flap in 2
      female patients (23 and 70 years old) for urethral stricture (posttraumatic and
      postinflammatory origin). We used as a patch a pedicle skin flap obtained from
      the labia minora. The pedicle flap is slid beneath the vulvovaginal wall, until
      the urethra is reached. RESULTS: In both cases a normal micturition was obtained,
      and cystourethrography after 24 months showed a good urethral silhouette, without
      residual urine. CONCLUSION: The pedicle labial urethroplasty seems to be a
      reliable technique for the repair of urethral strictures.

PMID- 12187037
TI  - Urological complications in renal transplantation: long-term follow-up of the
      Woodruff ureteroneocystostomy procedure in 433 patients.
AB  - PURPOSE: The two major types of urologic problems after renal transplantation are
      urinary leakage and obstruction. In this study, we report the urological
      complications of renal transplantations performed in our hospital during a 22
      year period. PATIENTS AND METHODS: Between 1978 and 2000, 433 consecutive
      patients underwent renal transplantation. Of those transplants, 50 were cadavers
      and 383 were living-related donor transplantation. All ureteroneocystostomies
      were performed with the same technique described by Woodruff. RESULTS: Urological
      complications developed in 19 (4.23%) recipients. Those complications were
      urinary leakage in 9 (2%), ureteral obstruction in 9 (2%) and ureteral necrosis
      in 1 patient (0.23%). All complications occurred during the 6-month postoperative
      period and after re-operation or conservative management no graft or patient was
      lost due to urological complications. CONCLUSIONS: The quoted overall rate of
      urological complications varies from 2.9 to 12.5%; our complication rate was
      4.23%. This relatively low rate is probably due to the Woodruff
      ureteroneocystostomy technique.

PMID- 12187038
TI  - Importance of transition zone biopsies in patients undergoing ultrasound-guided
      prostate systemic biopsies for the first time.
AB  - INTRODUCTION: We analyze the efficacy of routine transition zone biopsies in
      patients undergoing ultrasound-guided systemic prostate biopsies for the first
      time because of a suspicious digital rectal examination or an elevated serum
      prostate-specific antigen (PSA) level. PATIENTS AND METHODS: During systemic
      prostate biopsy two or four additional transition zone biopsies were performed in
      192 consecutive patients: in 182 because of a serum PSA concentration >4.1 ng/ml
      and in 10 because of a suspicious digital rectal examination and a serum PSA
      level <4.0 ng/ml. RESULTS: The overall prostate cancer detection rate was 37.5%
      (72/192). In 24 patients (33.3%), cancer was only detected in the peripheral
      zone, in 3 (4.2%) only in the transition zone, and in 45 (62.5%) in both zones.
      CONCLUSION: Transition zone biopsies performed at the first time of systemic
      prostate biopsy seem to have a low efficacy.

PMID- 12187039
TI  - Trimethoprim versus gentamicin for the prevention of bacteriuria following
      transrectal biopsy of the prostate--do patients need additional anaerobic cover?
AB  - OBJECTIVES: To study the incidence of aerobic and anaerobic bacteriuria in
      patients undergoing transrectal ultrasound-guided biopsies of the prostate. A
      comparative assessment of efficacy of trimethoprim with gentamicin for the
      prevention of bacteriuria following the transrectal biopsy of the prostate. To
      assess the need for additional prophylaxis against anaerobes for patients
      undergoing transrectal biopsies of the prostate gland. PATIENTS AND METHODS: In a
      pilot study during 1995-1997, all the patients undergoing transrectal ultrasound
      guided biopsy of the prostate were randomised to receive either trimethoprim or
      gentamicin prophylaxis prior to the procedure. Midstream urine (MSU) samples were
      taken just prior to biopsy and 72 h later. A patient questionnaire to determine
      the symptoms of urinary tract infection (UTI) accompanied the 72-hour MSU request
      form. Urine samples were cultured aerobically, using a semiquantitative technique
      if dipstick analysis revealed the presence of blood, pus cell or nitrite. In
      addition to the routine aerobic culture, post-biopsy samples were also cultured
      for anaerobes by direct and enrichment methods. Bacteriuria was defined as a pure
      or mixed growth of 10(5) colony-forming units/ml. Fisher's test of exact
      probability was used for statistical analysis. RESULTS: 115 patients were
      available for final analysis. 53 had received gentamicin and 62 trimethoprim.
      Four patients had pre-existing bacteriuria (3.5%), 3 in the trimethoprim group
      and 1 in the gentamicin group. Post-operative bacteriuria developed in 5 patients
      given gentamicin (9.4%) and 1 given trimethoprim (1.6%). This difference was not
      statistically significant (p = 0.085). Post-procedure bacteriuria was
      asymptomatic in all but 1 case. Anaerobes were detected in only 5 MSUs (4.3%)
      post-biopsy. CONCLUSION: Though there was no statistical significant difference
      in the rates of bacteriuria following administration of trimethoprim and
      gentamicin, data appear to favour trimethoprim prophylaxis. Further studies are
      warranted. Transrectal biopsy of the prostate is associated with a low incidence
      of anaerobic UTI. In view of the very low incidence of anaerobic bacteriuria,
      routine antibacterial prophylaxis against anaerobes does not appear to be
      justified.

PMID- 12187040
TI  - Less calcium in cremaster muscles of boys with undescended testis supports a
      deficiency in sympathetic innervation.
AB  - In addition to an increase in contractility, contracted fibers and small and
      electron-dense mitochondria have suggested an increase of cytosolic Ca(2+) within
      the cremaster muscles (CM) associated with undescended testis. Therefore, the
      Ca(2+) content of CM associated with an undescended testis was determined and
      compared with the Ca(2+) content associated with inguinal hernia and hydrocele
      and in internal oblique muscles. CM samples from boys with undescended testis (n
      = 9), inguinal hernia (n = 15), and hydrocele (n = 7) and from girls with
      inguinal hernia (n = 8) were obtained. The calcium contents of these samples and
      of samples from internal oblique muscle (n = 6) were determined by atomic
      absorption spectrophotometry. While the Ca(2+) contents of CM from boys with
      undescended testis and from girls with inguinal hernia were similar (p > 0.05),
      the internal oblique muscle and the CM from boys with inguinal hernia and
      hydrocele contained more Ca(2+) than CM from boys with undescended testis (p <
      0.05). Despite evidence of an increase in cytosolic calcium, the decrease in
      total calcium content suggests a decrease in the adenylyl cyclase activity, thus
      inhibition of influx of Ca(2+), but an increase in phospholipase C activity, and
      generation of more inositol 1,4,5-trisphosphate and mobilization of calcium from
      internal stores. Since the sympathetic system acts through adenylyl cyclase in
      striated muscles and is sexually dimorphic, similar Ca(2+) contents as
      encountered in girls suggest an alteration in the balance of autonomic
      innervation against the sympathetic system in boys with undescended testis.

PMID- 12187041
TI  - A reevaluation of the structures accepted to represent the postnatal
      gubernaculum.
AB  - INTRODUCTION: The structure called the residual gubernaculum (G) has been
      evaluated to define its origin. MATERIALS AND METHODS: Girls operated for
      inguinal hernia (n = 7) and boys operated for undescended testis (n = 12),
      inguinal hernia (n = 7), hydrocele of the cord (n = 1), and ectopic (n = 1) and
      entrapped (n = 1) testes were evaluated. Attachments of the structures coursing
      distally from the sacs were identified, and they were removed en block. Three
      samples, first from the distal part of the sac with the beginning of the fibrous
      structure, second from the midportion, and third from the most distal part, were
      prepared and stained with hematoxylin-eosin, trichrome and elastic van Gieson.
      Histologic structures within the samples were determined and compared with Mann
      Whitney U test. RESULTS AND CONCLUSIONS: Structures called the residual G
      differed from the walls of accompanying sacs by only the absence of mesothelial
      lining. Therefore, the structure called the residual G in boys with an
      undescended testis and the round ligament in girls actually represent the
      obliterated processus vaginalis.

PMID- 12187042
TI  - The plication procedure for penile curvature: surgical outcome and postoperative
      sexual functioning.
AB  - OBJECTIVE: This study evaluates the patients' judgement of the surgical outcome
      of the plication procedure, as described by Schroder and Essed, and the
      postoperative sexual functioning of patients with congenital curvatures and
      Peyronie's disease. PATIENTS AND METHODS: Of 98 patients treated for penile
      curvatures between 1985 and 1996, 85 patients received postoperatively a
      'Questionnaire Assessing the Outcome of Surgery' and a short version of the
      'Questionnaire for Screening Sexual Dysfunctions'. RESULTS: 28 patients with
      congenital curvatures and 31 with Peyronie's disease were evaluated. 75% of the
      patients with congenital curvatures and 58% of the patients with Peyronie's
      disease were satisfied with the result. Patients treated for Peyronie's disease
      reported diminished penile length and inability to have sexual intercourse more
      often than patients with congenital curvatures (90 vs. 64%, and 29 vs. 0%). After
      correction for age, patients with Peyronie's disease were less satisfied with
      their present sex life, had more frequent erectile problems and more trouble with
      considerable sexual desire than a group of 42 controls. For patients with
      Peyronie's disease satisfaction with the result was positively correlated with
      satisfaction with their present sex life and negatively correlated with the
      frequency of erectile problems. For patients with congenital curvatures
      satisfaction with the result was negatively correlated with both a postoperative
      curvature and a repeat operation. CONCLUSIONS: Some patients with Peyronie's
      disease may not benefit from surgical correction (alone). Because of the
      occurrence of sexual problems, future evaluation of the role of pre- and
      postoperative sexological counselling in achieving better results is recommended.

PMID- 12187043
TI  - Subsequent activation of mitogen-activated protein kinase after adhesion of
      transitional cell cancer cells to fibronectin.
AB  - INTRODUCTION: In the process of tumor invasion and metastasis, interactions
      between tumor cells and extracellular matrix play a crucial role. Recently, it
      was shown that fibronectin binding to fibronectin receptor promotes mitogen
      activated protein kinase (MAPK) activation after tyrosine phosphorylation of
      focal adhesion kinase (FAK). We investigated these signal transduction events in
      transitional cell cancer (TCC) cells. MATERIALS AND METHODS: (1) The adhesion of
      T24 cells, a fibronectin-receptor-positive TCC cell line, to fibronectin was
      investigated; (2) the MAPK activation after fibronectin stimulation in bladder
      cancer cell lines was examined by Western blotting using an antiactive MAPK
      antibody, and (3) FAK, Sos, and Grb-2 were also examined by Western blot
      analysis. RESULTS AND CONCLUSIONS: T24 cells adhered to fibronectin-coated dishes
      more quickly than to the noncoated dishes. Fibronectin stimulation induced
      activation of MAPK in T24, SCaBER, and HT1376 cells. However, activated MAPK was
      not detected in RT4 cells which do not express alpha(5)beta(1) integrin (major
      fibronectin receptor) after fibronectin stimulation. T24, SCaBER, and HT1376
      expressed FAK and Sos. RT4 showed little FAK and Sos expression. Grb-2 was
      expressed in all cell lines. Adhesion of fibronectin-receptor-positive TCC cells
      to fibronectin activates the MAPK cascade, possibly resulting in activation of
      tumor cells.

PMID- 12187044
TI  - Chromosomal aberrations in transitional cell carcinoma: its correlation with
      tumor behavior.
AB  - OBJECTIVE: Fluorescence in situ hybridization (FISH) was used to study numerical
      aberrations of chromosomes 1, 3, 7, 9, 11, 15, 17, X and Y in interphase nuclei
      of 16 transitional cell carcinoma (TCC) cell lines of the urinary tract. The
      number of chromosomal signal copies was compared with the DNA ploidy and
      correlated with the cellular grading and original tumor staging. METHODS: The
      single-target FISH with the repetitive DNA probes for chromosomes 1, 3, 5, 7, 9,
      11, 15, 17, X and Y were performed in 16 human TCC cell lines. For each test
      specimen, a minimum of 200 nuclei were analyzed. The number of fluorescent
      signals per nucleus was recorded. Tumor ploidy was analyzed using the DNA
      propidium iodide flow cytometric method. These results were correlated with tumor
      grade and stage. RESULTS: In two diploid TCC cell lines, on average 67% of
      detected chromosomes were di-(i)somic. In 14 aneuploid TCC cell lines, on average
      only 10% (0-44%) of detected chromosomes were di-(i)somic. Chromosome X was
      completely changed into polysomism in 16 TCC cell lines (native male:female ratio
      = 12:4) but was unrelated to tumor grade or stage. Chromosome Y was lost in 10
      out of 12 (83%) TCC cell lines which originated from male patients but was
      unrelated to tumor grade or stage too. 31% of chromosomes 11 and 15 were disomic
      in 16 TCC cell lines, 38% of chromosome 3 was monosomic, and 81-88% (83 in
      average) of chromosomes 1, 7, 9, 17 were polysomic. Disomic chromosome 11
      associated with lower grade TCC and disomic chromosome 15 associated with higher
      grade TCC were noted (p < 0.01). Higher incidence of low stage tumors was
      observed in TCC cell lines with disomic chromosome 11 or chromosome 15 (p <
      0.01). There was no correlation in somatic status of chromosomes 1, 7, 9, 17 with
      tumor grade and stage. CONCLUSIONS: The results of the study demonstrate that
      polysomism of chromosomes 1, 7, 9, 17 and X occurs in most of the TCC cells with
      aneuploidy. The stability of chromosomes 11 and 15 is closely related to tumor
      grade and stage. The role of chromosome Y loss and monosomism of chromosome 3 in
      oncogenic relevant of bladder cancer is still unclear.

PMID- 12187046
TI  - Sarcomatoid carcinoma of urinary bladder: immunohistochemical study of an
      uncommon case.
AB  - A case of sarcomatoid carcinoma of the bladder is reported herein.
      Immunohistochemical staining with human pancytokeratin antibody was negative,
      while vimentin staining was strongly positive, suggesting a diagnosis of sarcoma
      of the bladder. Further immunohistochemical analysis revealed positivity for
      AE1/AE3 cytokeratins, permitting a correct diagnosis of sarcomatoid carcinoma of
      the bladder. It can be difficult to distinguish between sarcomatoid carcinoma,
      undifferentiated carcinoma and sarcoma, particularly if the biopsy specimens are
      of small size. In rare cases, sarcomatoid tumors may express epithelial markers
      different from those revealed by human pancytokeratin staining.

PMID- 12187045
TI  - Early and late complications of double pigtail ureteral stent.
AB  - OBJECTIVES: To analyze the early and late complications of indwelling ureteral
      stents in a series of 146 patients with nephroureteral lithiasis. MATERIALS AND
      METHODS: 146 patients with obstructing nephrolitiasis were treated for urinary
      diversion with double pigtail ureteral stent before extracorporeal shock-wave
      lithotripsy (ESWL) and following ureterorenoscopic treatment of lithiasis. All
      patients were scheduled for stent removal or replacement at specific 3-month
      intervals until stone-free status was achieved. RESULTS: Early complications
      during the first 4 weeks after stent insertion were stent discomfort (37.6%),
      irritative bladder symptoms (18.8%), hematuria (18.1%), bacteriuria (15.2%),
      fever >104 degrees F (12.3%) and flank pain (25.3%); late complications included
      hydronephrosis (5.7%), and stent migration (9.5%), encrustation (21.6%),
      fragmentation (1.9%) and breakage (1.3%). CONCLUSIONS: Ureteral stents have
      proven to be an invaluable tool for endourologists. Morbidity is minimal for up
      to three months but longer indwelling times are associated with an increasing
      frequency of incrustation, infections, secondary stone formation and obstruction
      of the stented tract.

PMID- 12187047
TI  - Major complex pelvic arteriovenous malformation in a patient with Down syndrome.
AB  - Pelvic arteriovenous malformations (AVM) are rare, and the treatment of this
      condition presents an interesting challenge. We report the first case of a major
      AVM in a patient with Down syndrome which was revealed by a massive hematuria.
      Arteriography showed a bilateral complex iliac artery malformation. The first
      proximal embolization (unilateral) did not prevent bladder hemorrhage, and the
      second distal (bilateral) immobilization produced bladder necrosis. However, the
      patient died despite an emergency cystectomy.

PMID- 12187048
TI  - Extraosseous Ewing's sarcoma of the kidney.
AB  - Extraosseous Ewing's sarcoma/primitive neuroectodermal tumor (EES/PNET) of the
      kidney is an uncommon entity and usually arises from the retroperitoneum and
      paraspinal region. We report a case of renal EES/PNET and discuss its clinical
      features, histological findings and management.

PMID- 12187049
TI  - An unusual primary renal lymphoma.
AB  - A case of primary renal lymphoma (PRL) in a 78-year-old man is reported. The
      tumor was found by computed tomography during a check-up for hematuria and weight
      loss. Histologic and immunohistochemical analyses of this tumor revealed features
      typical of low-grade lymphoma with localized amyloid deposition. PRL is a rare
      disease and only a few cases have been reported previously. To our knowledge,
      there have been no other reports of PRL with localized amyloid deposition.

PMID- 12187050
TI  - Malignant peripheral nerve sheath tumor of the urinary bladder in von
      Recklinghausen disease.
AB  - A case of malignant peripheral nerve sheath tumor of the bladder in a 57-year-old
      man with multiple neurofibromatosis type 1 is presented. The patient had a recent
      history of a transurethrally resected bladder ganglioneuroma. A probable
      histogenetic association between these two extremely rare neoplasms is proposed.

PMID- 12187051
TI  - Giant calculus of the posterior urethra following recurrent penile urethral
      stricture.
AB  - A case of an unusually large, proximal urethral calculus located very close to
      the external sphincter and caused by recurrent urethral stricture is presented.

PMID- 12187052
TI  - Testicular amyloidosis.
AB  - Rapid testicular enlargement is usually strongly suggestive of tumor. Primary
      testicular infiltration due to amyloidosis is rare. We report a new case of
      primary testicular amyloidosis in a 72-year-old white man who presented with a
      short history of painless right testis enlargement.

PMID- 12187053
TI  - Torsion of spermatocele: a rare manifestation.
AB  - Torsion of a spermatocele on its pedicle is an extremely rare clinical condition
      that mimics acute testicular torsion. This rare condition has not been well
      characterized. Here, we report a case of torsion of a spermatocele. The present
      case is the 5th case of torsion of a spermatocele and the first report in a
      patient with a history of scrotal trauma. A tender cystic mass adjacent to the
      normally appearing testicle in the scrotum is highly significant for the
      differentiation from other types of acute scrotum. Torsion of a spermatocele
      should be considered a differential diagnosis of acute scrotum in adolescents and
      adults.

PMID- 12187054
TI  - Small cell/neuroendocrine carcinoma may be a more common phenotype in advanced
      prostate cancer.

PMID- 12187055
TI  - Medulloblastoma metastatic to the suprasellar region at diagnosis: a report of
      six cases with clinicopathologic correlation.
AB  - The presence of metastatic disease in patients newly diagnosed with
      medulloblastoma remains one of the most important prognostic factors that
      determines event-free survival. In the present study, anatomic distribution and
      the signal characteristics and enhancement patterns of subtle anterior third
      ventricular recess metastases were compared with those of the original tumor;
      medical records were reviewed for clinical presentation, surgical stage,
      treatment and long-term outcomes. All foci were clinically occult; 5 out of 6 had
      negative cerebrospinal fluid cytology, and in 4 out of 6, the only evidence of
      metastatic disease was documented suprasellar disease that resolved or
      significantly improved following irradiation and chemotherapy. Histologically, 3
      of the 6 patients had tumors with large cell/anaplastic features, a significant
      increase compared to the expected incidence of 4-8.8%. Patients with tumors that
      show large cell/anaplastic features may be at higher risk for early metastatic
      involvement of this unusual site.

PMID- 12187056
TI  - An unusual tuberous sclerosis case presenting with fibrillary astrocytoma.
AB  - Tuberous sclerosis (TS) is an autosomal dominant disorder. It is characterized by
      hamartomatous lesions in various organs such as the brain, skin, kidneys and
      heart. Subependymal and parenchymal nodules occur in the cerebrum. Although giant
      cell astrocytoma may develop from these subependymal nodules, tumor formation is
      very rare in the cortical nodules. We present the clinical, computed tomography
      and magnetic resonance imaging findings of a fibrillary astrocytoma originating
      from a cortical tuber in a 4-year-old female with TS.

PMID- 12187057
TI  - Neurofibromatosis type 1 and the pediatric neurosurgeon: a 20-year institutional
      review.
AB  - Children with neurofibromatosis type 1 (NF1) undergo costly surveillance scanning
      for a variety of asymptomatic central nervous system lesions whose natural
      history is poorly understood. We performed a 20-year retrospective chart review
      of 25 patients with clinically proven NF1 who required surgery (group A) and
      contrasted this cohort with 150 NF1 patients who did not require surgery (group
      B). In group A, 52% of patients underwent multiple procedures for more than one
      lesion (p = 0.043). Group A patients were further distinguished from those in
      group B by exhibiting a greater number of optic gliomas (p = 0.015), nonoptic
      intracranial tumors (p = 0.006), cranial nerve (p = 0.000), paraspinal (p =
      0.0062), craniofacial (p = 0.001) and visceral (p = 0.03) neurofibromas and
      moyamoya disease (p = 0.00), as well as a higher frequency of seizure disorder,
      sphenoid wing dysplasia and poor academic performance. Gadolinium enhancement
      occurred in 43% of optic gliomas, 50% of parenchymal gliomas, 100% of cranial
      nerve, 100% of plexus, 67% of paraspinal, 50% of craniofacial and 50% of visceral
      neurofibromas in group A, while only 1 group B tumor enhanced. In group A,
      radiological progression occurred after a median of 4 years from initial
      diagnosis for optic gliomas as well as cranial nerve, plexus and visceral
      neurofibromas, 2 years for paraspinal neurofibromas and brainstem gliomas and 2.7
      years for craniofacial neurofibromas. Only 1 tumor progressed in group B.
      Therefore, a small subgroup of NF1 patients (12.5%) who require treatment are at
      risk of subsequently needing further surgical attention, whereas a larger group
      of NF1 patients (87.5%) carry an indolent form of the disease. We recommend
      imaging for asymptomatic, gadolinium-enhancing lesions every 2 years for optic
      pathway and parenchymal gliomas and cranial nerve and visceral neurofibromas, and
      every year for brainstem gliomas and paraspinal as well as craniofacial
      neurofibromas. Nonenhancing optic pathway lesions could be followed up
      radiographically much less often since they do not show progression.

PMID- 12187058
TI  - Cervical and thoracic dermal sinus tracts. A case series and review of the
      literature.
AB  - Cervical and thoracic dermal sinus tracts (DSTs) account for 1 and 10%,
      respectively, of all DSTs. Few case reports describe this diagnosis. To
      characterize this entity, a 30-year retrospective audit was utilized to identify
      cases. Nine cases were identified, five of which were cervical and four thoracic.
      Four cases less than 1 year old presented with skin findings and no neurologic
      deficit. All five cases greater than 1 year old presented with neurologic
      findings. Initial examination revealed changes in motor function (n = 5),
      sensation (n = 4), reflexes (n = 5), gait (n = 4) and altered bowel/bladder
      function (n = 2). Eight patients had cutaneous findings and 7 had bifid spinous
      processes overlying tract entry into the dura. Operative findings included 6
      buckled tethered cords, opacified arachnoid or frank arachnoiditis in 4 patients,
      2 tract CSF leaks, 2 split cord malformations and 2 intradural tumors. Mean
      follow-up was 36 months. All infants remained neurologically intact. Four of the
      5 patients greater than 1 year old demonstrated improvement; 1 continued with a
      stable deficit. This series of cervical and thoracic DSTs highlights the need for
      close attention to skin lesions in infants and consideration of retethering or
      tumor in patients with previous resections who deteriorate. Definitive operation
      including intradural exploration should be performed with the initial operation
      in an attempt to obviate future complications.

PMID- 12187060
TI  - Spontaneous resolution of a prepontine arachnoid cyst. Case report and review of
      the literature.
AB  - Prepontine arachnoid cysts are rare developmental anomalies that occur almost
      exclusively in children. The symptomatic child typically suffers from
      hydrocephalus, visual impairment, endocrine dysfunction and/or cranial
      neuropathies. Some cysts, however, are discovered incidentally upon prenatal or
      postnatal imaging for other indications. While there is little doubt that
      surgical treatment should be initiated to help the symptomatic child, appropriate
      therapy for the asymptomatic patient is unclear. Although arachnoid cysts are
      often managed conservatively using serial imaging, the consequences of injury to
      surrounding structures with prepontine cysts often lowers the threshold for
      intervention. The natural history of asymptomatic prepontine arachnoid cysts is
      unknown. It has been reported that some cysts enlarge and cause symptoms, whereas
      others are stable for years. This report describes an index case of spontaneous
      resolution of a prepontine arachnoid cyst in a female infant over a 5-year
      period.

PMID- 12187059
TI  - Neuropathological findings in a child with slit ventricle syndrome.
AB  - The histopathological changes in shunted hydrocephalic children with slit
      ventricle syndrome have never been described. Periventricular gliosis is presumed
      to be an important feature. A girl who was shunted in infancy following
      meningitis developed headaches at 10 years of age and suffered a respiratory
      arrest, from which she was resuscitated. CT scan of the head showed very small
      ventricles. A diagnosis of slit ventricle syndrome was made. She died 33 h later.
      Autopsy revealed a large head and brain, small ventricles with glial adhesions,
      obstruction of the cerebral aqueduct, complete obstruction of the shunt catheter
      and reactive astroglia in the periventricular white matter. The latter change was
      no more severe than in hydrocephalic children with enlarged ventricles who have
      died following shunt failure. Periventricular astrogliosis may not necessarily be
      the major determinant of the slit ventricle syndrome.

PMID- 12187061
TI  - Stroke and pediatric human immunodeficiency virus infection. Case report and
      review of the literature.
AB  - Stroke is an uncommon complication in pediatric patients with acquired
      immunodeficiency syndrome (AIDS). However, with the increasing life span of this
      patient population, more cases of stroke are being reported. We report the case
      of a 13-year-old girl with a known history of AIDS who presented with new-onset
      seizures and right hemiparesis. Serial imaging studies revealed progressive
      occlusion of the left middle cerebral artery and both anterior cerebral arteries
      with development of collateral circulation. The workup for other etiologies of
      stroke was negative. This nonatherosclerotic occlusive disease is most likely
      secondary to vasculopathy caused by the human immunodeficiency virus (HIV). HIV
      infection should be included in the differential diagnosis of children who
      present with seizures, mental status change or focal neurological deficits.
      Treatment options are limited. The different prognoses associated with the
      etiologies of stroke in this patient population mandate a careful and thorough
      evaluation.

PMID- 12187062
TI  - Two newborn children with large hemorrhages from arteriovenous malformations.

PMID- 12187063
TI  - Transcranial ultrasound imaging in a premature infant.

PMID- 12187064
TI  - Neoadjuvant chemotherapy with sequential methotrexate and 5-fluorouracil
      scheduling, epirubicin and cisplatin for locally advanced bladder cancer.
AB  - INTRODUCTION: Transitional cell carcinoma of the bladder is moderately sensitive
      to chemotherapy. Notably, the methotrexate, doxorubicin, vinblastine and
      cisplatin regimen was found to produce a high overall response rate and a modest
      survival advantage. However, toxicity was significant and the therapy rarely
      results in long-term disease-free survival. In several clinical series,
      sequentially delivered methotrexate and 5-fluorouracil followed by leucovorin
      rescue in expectation of a biochemical modulation has a higher response rate.
      METHODS: The combination chemotherapy using sequential methotrexate and 5
      fluorouracil scheduling, epirubicin and cisplatin (MFAP regimen) for locally
      advanced bladder cancer was evaluated in a neoadjuvant setting. Thirty-seven
      patients (32 males and 5 females) were enrolled in this study. RESULTS: Six
      (16.2%) of the patients had complete responses and 26 (70.3%) had partial
      responses to the therapy amounting to a response rate of 86.5%. At follow-up, 10
      of 13 patients (76.9%) who underwent bladder preservation had not developed
      muscle-invasive recurrence of the disease and kept their bladder. There is no
      statistical difference of the survival rate between the cystectomy group and the
      bladder preservation group (p = 0.86). Toxicity was relatively mild but with some
      severe myelotoxic effects. CONCLUSIONS: MFAP represents an active regimen in the
      treatment of locally advanced bladder cancer with a moderate toxicity profile.

PMID- 12187065
TI  - Isolated leptomeningeal carcinomatosis (carcinomatous meningitis) after taxane
      induced major remission in patients with advanced breast cancer.
AB  - OBJECTIVES: To identify the incidence of leptomeningeal carcinomatosis (LMC), as
      the first site of systemic progression, in breast cancer patients after having
      obtained a major response (CR or near CR) to first-line taxane-based chemotherapy
      and compare these findings in retrospect with a matched-pair group of historical
      control patients from our database treated with nontaxane regimens. PATIENTS AND
      METHODS: Patients with histologically proven breast cancer having either
      metastatic disease or high-risk locoregional disease that were entered into
      treatment protocols with first-line taxane (paclitaxel or docetaxel) plus
      anthracyclines or mitoxantrone combinations and developed LMC as the first
      evidence of progression after major response (CR or >80% PR) were analyzed in the
      present study (n = 155), and compared, as regards the incidence of LMC, to a
      matched-pair retrospective group of 155 patients treated with nontaxane regimens
      in our unit. RESULTS: Seven patients with a median age of 54 years (range 40-70)
      developed LMC as their first evidence of progression after taxane-based regimens
      with a median interval of 6 months (range 2-18) from start of treatment to
      diagnosis of LMC. Five patients received intrathecal (i.t.) methotrexate
      treatment and whole brain radiotherapy (RT), while 1 patient received i.t.
      methotrexate and RT to the lumbar spine. Two patients responded to treatment for
      LMC, while 2 achieved stable disease and 3 progressed. Two patients had elevated
      cerebrospinal fluid tumor markers (more than serum marker levels) that proved
      useful in monitoring response to treatment. Median survival after LMC was 3.6
      months (range 1-17+) and correlated positively to the interval from the
      initiation of taxane-based therapy to LMC (r = 0.84, p = 0.019). Seven out of 86
      responders (8.13%) in the taxane group versus 1 out of 72 responders (1.4%) in
      the non-taxane-treated group developed LMC as the first sign of progression after
      a major response to first-line chemotherapy (p < 0.1). CONCLUSIONS: LMC after a
      major response to front-line taxane-based regimens represents a grave disease
      manifestation and its incidence appears increased, but not significantly so, when
      compared retrospectively to non-taxane-treated patients. Prospective evaluation
      of the incidence of LMC after taxane versus non-taxane-based treatment from large
      randomized multi-institutional trials is warranted and identification of
      potential prognostic factors might help to identify patients requiring
      appropriate prophylactic therapy.

PMID- 12187066
TI  - Irinotecan (CPT-11) and cisplatin as first-line chemotherapy for advanced ovarian
      cancer.
AB  - OBJECTIVE: To evaluate the efficacy and toxicity of a combination of irinotecan
      (CPT-11) and cisplatin as first-line chemotherapy in advanced ovarian cancer.
      METHODS: Twenty-six patients with previously untreated advanced epithelial
      ovarian cancer were enrolled in this study. CPT-11 60 mg/m(2) was administered
      intravenously on days 1, 8, and 15 in combination with cisplatin 60 mg/m(2) on
      day 1. Cycles were repeated every 28 days for at least two cycles. The median
      patient age was 55 years (range, 37-75), and the median performance status was 1.
      RESULTS: Objective responses were recorded in 19 of 25 eligible patients (76%;
      95% confidence interval, 55-91%). Complete responses were obtained in 2 patients
      (8%), and partial response in 17 patients (68%). Stable disease was recorded in 2
      patients (8%) and progressive disease in 2 (8%). The median time to response was
      62 days (range, 28-234 days). The median survival time for all 25 patients was
      30.9+ months (range, 4.1-60.0+ months). The major toxic effects were leukopenia,
      neutropenia, and diarrhea. Grade 3 or 4 leukopenia, neutropenia, and diarrhea
      occurred in 17 (68%), 20 (83.3%), and 5 patients (20%), respectively.
      Thrombocytopenia was less common. No treatment-related deaths occurred.
      CONCLUSION: The combination of CPT-11 and cisplatin showed significant activity
      in chemotherapy-naive patients with advanced ovarian cancer. Neutropenia was the
      dose-limiting adverse effect, whereas diarrhea was mainly mild to moderate.

PMID- 12187068
TI  - Vinorelbine and cisplatin for the treatment of recurrent and/or metastatic
      carcinoma of the uterine cervix.
AB  - BACKGROUND: To test the clinical activity and toxicity profile of the combination
      regimen of vinorelbine and cisplatin in a series of patients with carcinoma of
      the cervix uteri with de novo metastatic disease or recurrent disease after
      previous therapy. The main aims of the study included analysis of objective
      response rates, toxicity, and time to progression. PATIENTS AND METHODS: Forty
      two eligible patients were enrolled into the trial and treated with cisplatin 80
      mg/m(2) on day 1 and vinorelbine 25 mg/m(2) on day 1 and 8. This regimen was
      repeated every 21 days upon resolution of toxicity for 3 cycles before response
      assessment. Enrolled patients had a median age of 53 years, a median ECOG
      performance status of 1, and mostly a squamous cell histology (86%). Sixteen
      patients (38%) were treatment-naive since first diagnosed with widespread
      metastatic disease, 7% had only previous surgery, 31% radiotherapy, and 24% both
      radiation and surgical therapy. In previously radiated patients, 21% of patients
      had disease only within the radiation fields, 21% only outside the radiation
      fields, and 12% both inside and outside the radiotherapy portals. RESULTS: All
      patients were evaluable for response analysis. A complete response was achieved
      in 5 patients (12%), and a partial response in 15 cases (36%) for an overall
      response rate of 48% (95% CL 22-52%). Patients with recurrent disease within the
      previous radiation field (including those also with disease outside the radiation
      fields) showed a 28% overall response rate with no complete response, while
      patients with disease previously untreated with radiotherapy or with tumour
      deposits only outside of ratiation portals yielded a 57% overall response rate
      with a 18% complete response rate. Only 1 out of 8 patients with performance
      status 2 showed a major response (12%). Median time to progression was 5.6 months
      (range 2.0-14 months). The median overall survival of the whole series was 9.1
      months. Hematological toxicity was the most frequent side-effect. Grade 3
      vomiting was recorded in 9 patients (21%), and mild mucositis in 14% of patients.
      Grade 3 neutropenia was observed in 21% of patients, while grade 4 in 12% of
      cases with neutropenic fever was seen in 4 cases. Sixteen patients (38%)
      complained of grade 1-2 constipation, while grade 1-2 peripheral neuropathy was
      seen in 8 patients (19%). CONCLUSIONS: The results achieved in this trial suggest
      that the combination regimen of vinorelbine and cisplatin may be safely given to
      patients with metastatic and/or recurrent carcinoma of the uterine cervix. This
      regimen is active at least in terms of objective response rates. Although
      satisfactory results are still lacking, these results suggest that the
      vinorelbine-cisplatin regimen is worthy of further studies and may represent the
      basis for the development of new active regimens.

PMID- 12187067
TI  - Pegylated liposomal doxorubicin with vinorelbine in metastatic breast carcinoma.
      A phase I-II clinical investigation.
AB  - A multicenter phase I-II trial was carried out with the aim of identifying the
      dose-limiting toxicity and the maximum tolerated dose of vinorelbine (VNR) in
      combination with pegylated liposomal doxorubicin at a dose of 20 mg/m(2) every 15
      days in patients with metastatic breast carcinoma. In the phase I part of the
      trial, VNR was given at a dose of 20 mg/m(2) every 15 days to a group of 3
      patients. In absence of unacceptable toxicity, VNR was escalated to 25, 30, and
      35 mg/m(2) for subsequent groups of 3 patients, until the dose-limiting toxicity
      was reached. No case of palmar-plantar erythrodysesthesia was recorded in these
      patients. Grade 4 neutropenia, grade 3 thrombocytopenia, and grade 3 mucositis
      were the dose-limiting toxicities recorded in patients treated with VNR 35
      mg/m(2). These side effects caused a substantial decrease in programmed dose
      intensity. Therefore 30 mg/m(2) was considered the maximum tolerated dose of VNR
      in combination with pegylated liposomal doxorubicin 20 mg/m(2), both given every
      15 days. These dosages were employed for the treatment of further 18 patients
      included in phase II of the study. The overall response rate, calculated
      according to an intention to treat analysis, was 63% (95% CI: 44-80%), with 2
      patients achieving a complete response. The median time to progression was 7.0
      months or more (range 2-14 months). Median duration of objective responses was
      8.4 months or more. The duration of the 2 complete responses was 9 and 14 months,
      respectively. Median duration of survival was 16.0 months or more (range from 4.0
      to >or=24.0). Toxicity was generally mild and easily manageable. Neutropenia and
      mucositis were the most frequently recorded side effects. A case of palmar
      plantar erythrodysesthesia was recorded in phase II of the study. In conclusion,
      the maximum tolerated dose of VNR in association with pegylated liposomal
      doxorubicin is 30 mg/m(2) on a bimonthly schedule. Moreover, the combination of
      VNR and pegylated liposomal doxorubicin is active against metastatic breast
      carcinoma and is associated with a good toxicity profile. Further studies with
      this combination regimen are warranted.

PMID- 12187069
TI  - Temozolomide in patients with glioblastoma at second relapse after first line
      nitrosourea-procarbazine failure: a phase II study.
AB  - OBJECTIVES: To investigate the efficacy of temozolomide (TMZ) in relationship to
      progression free survival at 6 months (PFS-6), median time to progression (TTP),
      response rate and toxicity, a phase II study was conducted in patients with
      recurrent glioblastoma multiforme (GBM) following surgery plus radiotherapy and a
      first-line regimen based on nitrosourea, procarbazine and vincristine. METHODS:
      Forty-two patients with GBM were administered TMZ at the dose of 150
      mg/m(2)/daily for 5 days every 4 weeks. RESULTS: The PFS-6 and at 12 months (PFS
      12) was 24% (95% Confidence Interval [CI] = 14-42%) and 8% (CI = 2-27%),
      respectively, with a median TTP of 11.7 weeks (CI = 9-22 weeks). The response was
      assessed in all 42 patients; we observed 2 complete responses (CR) (4.7%), 6
      partial responses (PR) (14.3%), and 9 stable disease (SD) (21.4%), with CR+PR =
      19% (CI = 7-31%). CONCLUSION: TMZ as a second line regimen is a valid option in
      patients with heavily pretreated GBM.

PMID- 12187070
TI  - Multicenter phase I study of irinotecan plus raltitrexed in patients with 5
      fluorouracil-refractory advanced colorectal cancer.
AB  - Irinotecan and raltitrexed are active against advanced colorectal cancer, act
      through different mechanisms, and have non-overlapping toxicity profiles. In
      vitro studies have shown a schedule-dependent synergism between both drugs. The
      aim of this multicenter study was to determine the maximum tolerated dose (MTD)
      of this combination. Patients with 5-fluorouracil-refractory, advanced colorectal
      cancer were eligible. Dose escalation consisted of irinotecan (250-350 mg/m(2) as
      a 60-min infusion) in combination with a fixed dose of raltitrexed (3 mg/m(2) as
      a 15-min infusion, 1 h after irinotecan). Courses were repeated every 21 days.
      Three to 6 patients were to be included at each dose level. Dose limiting (NCI
      CTC grade 3-4) toxicities (DLT) were assessed during the first 2 cycles. Thirteen
      patients were recruited (4, 3 and 6 in levels I, II and III, respectively). Main
      toxicity was diarrhea and asthenia, whereas myelotoxicity was mild. At level III,
      2/6 patients experienced DLT (grade 4 diarrhea and neutropenia). The MTD was not
      reached, but further dose escalation was not attempted. Among 12 patients with
      measurable disease, 2 partial responses were observed for an overall response
      rate of 17%. The combination of single-agent full doses of irinotecan (350
      mg/m(2)) and raltitrexed (3 mg/m(2)) in a 3-weekly schedule is feasible, with
      mild toxicity and a promising clinical activity. Diarrhea is the DLT, but it is
      not more common or severe than that described with irinotecan alone.

PMID- 12187071
TI  - DNA aneuploidy in relation to the combination of analysis of estrogen receptor,
      progesterone receptor, p53 protein and epidermal growth factor receptor in 498
      breast cancers.
AB  - BACKGROUND: Various studies have analyzed the relationships between new
      biological parameters and DNA ploidy for human cancer. However, the biological
      significance of DNA ploidy remains unclear, since there have so far been few
      studies analyzing DNA ploidy in relation to the combination of multiple such
      biological parameters. METHODS: Samples for the analysis of DNA ploidy, estrogen
      receptor (ER), progesterone receptor (PgR), p53 protein and epidermal growth
      factor receptor (EGFR) were prepared from the same frozen specimens of 498
      primary breast cancers. DNA ploidy was determined by flow cytometry, while ER and
      PgR were determined by an enzyme immunoassay. Both p53 protein and EGFR were
      determined by immunohistochemical analyses. RESULTS: Aneuploidy was significantly
      correlated with the absence of ER, the absence of PgR, the positivity of p53
      protein and the positivity of EGFR, and it was also significantly correlated with
      the combination of the absence of ER and PgR and the combination of the
      positivity of p53 protein and EGFR. A deviation in the four parameters was
      defined as the absence of ER, the absence of PgR, the positivity of p53 protein
      or the positivity of EGFR. As the number of deviations of these four biological
      parameters increased, the incidence of aneuploidy increased significantly (p <
      0.0001). Multivariate analysis also indicated that deviation of two, three or all
      four parameters were significant factors for DNA ploidy, while the p value
      decreased and the odds ratio increased as the number of deviations of the four
      biological parameters increased. CONCLUSIONS: DNA aneuploidy based on flow
      cytometric analysis reflects the accumulation of deviations in the four
      biological parameters investigated in the present study. The two facts that DNA
      aneuploidy reflects the accumulation of the aggressiveness of these biological
      parameters and that DNA aneuploidy consisted of heterogeneous characteristics
      which were represented by the deviation of each biological parameter should be
      taken into consideration when selecting treatment strategies for breast cancer.

PMID- 12187072
TI  - Nonmalignant oral keratinocytes from patients with head and neck squamous cell
      carcinoma show enhanced metabolism of retinoic acid.
AB  - BACKGROUND AND OBJECTIVE: Retinoids show promise in the treatment of various
      (pre)malignancies, including head and neck squamous cell carcinoma (HNSCC). It
      has been shown that metabolic pathways of retinoids are important in their
      anticancer effect and that these pathways may change during HNSCC carcinogenesis.
      We have previously reported that HNSCC cells have a 17-fold greater turnover rate
      of retinoic acid (RA) than normal oral keratinocytes from noncancer controls, and
      that the formation of polar metabolites such as 4-oxo-RA and 4-hydroxy-RA is only
      seen in HNSCC cell lines. We aimed to establish whether this altered retinoid
      metabolism is an intrinsic characteristic of HNSCC patients. METHODS: The normal
      mucosa of cancer and noncancer patients was the source of keratinocyte cultures.
      The cells were exposed to RA for various time periods, and the levels of various
      retinoids were measured in the culture medium and cell pellets with reverse-phase
      liquid chromatography. RESULTS: Cells from cancer patients were morphologically
      normal and showed no genetic aberrations (i.e. loss of heterozygosity). The RA
      turnover rate in normal oral keratinocytes of cancer patients was 15 times higher
      (p = 0.003) than that in normal oral keratinocytes of noncancer controls, with
      average turnover rates of 218.6 and 14.8 pmol/mg protein/h, respectively.
      Specific profiles of RA metabolites were similar. CONCLUSION: The observed higher
      RA metabolism in noncancer cells of HNSCC patients suggests that individuals with
      a relatively high RA turnover have an increased risk of developing HNSCC.

PMID- 12187073
TI  - Circulating levels of thrombopoietic and inflammatory cytokines in patients with
      acute myeloblastic leukemia and myelodysplastic syndrome.
AB  - BACKGROUND: The regulation of megakaryocytopoiesis and thrombopoiesis appears to
      be under the control of an array of hematopoietic growth factors. The regulatory
      mechanism of endogenous cytokines in circulating platelet counts of
      thrombocytopenic patients with acute myeloblastic leukemia (AML) and
      myelodysplastic syndrome (MDS) is still not clear. METHODS: We measured the serum
      levels of both thrombopoietic and inflammatory cytokines in peripheral blood and
      bone marrow samples collected from 52 patients with either AML or MDS along with
      35 normal control samples. The levels of thrombopoietin (TPO), interleukin (IL)
      11, IL-6, IL-8 and stem cell factor (SCF) were determined by ELISA. RESULTS:
      Platelet counts in the AML/MDS patients during initial diagnosis, chemotherapy
      and complete remission were 71.2 +/- 11.6, 47.2 +/- 6.1 and 181.4 +/- 26.3
      x10(9)/l, respectively. The median value of TPO in AML/MDS patients during
      diagnosis was 150.6 pg/ml and increased significantly during chemotherapy
      (median: 828 pg/ml; p < 0.05) but then decreased following complete remission
      (median: 221.4 pg/ml). However, these levels were all significantly higher in
      patients than in normal subjects (p < 0.05, p < 0.05 and p < 0.05; respectively),
      and no significant change was noted in the levels of IL-11 and SCF during
      treatment of patients or in normal controls. The level of IL-6 was not detectable
      in normal serum samples but was markedly increased in the AML/MDS patients
      (median level during diagnosis: 6.7 pg/ml; chemotherapy: 25 pg/ml; complete
      remission: 7 pg/ml). The level of IL-8 in patients with AML and MDS was markedly
      elevated during diagnosis (median: 27.5 pg/ml; range: 0-1,587 pg/ml), but
      decreased to the level of the normal controls when patients were under
      chemotherapy or in complete remission. CONCLUSIONS: The endogenous levels of TPO,
      IL-6 and IL-8 are elevated in the thrombocytopenic patients with AML and MDS. Our
      results are consistent with previous mechanistic studies and suggest that TPO and
      IL-6 may be active mediators of platelet production.

PMID- 12187074
TI  - High level of vascular endothelial growth factor in hemorrhagic pleural effusion
      of cancer.
AB  - Angiogenic cytokines, such as vascular endothelial growth factor (VEGF), basic
      fibroblast growth factor (bFGF) and angiogenin, are candidates for the induction
      of pleural effusions because they have been implicated in the induction of
      neovascularization, vascular permeability, and hemorrhage both in the
      inflammatory process and in tumor progression. Thus, we hypothesized that these
      angiogenic factors in effusion might be involved in the clinical manifestation of
      malignant pleural disease. We measured the levels of VEGF, bFGF, and angiogenin
      in pleural effusions and sera from 40 patients. Pleural effusions due to
      malignancy (1,350 pg/ml) contained significantly higher levels of VEGF than
      effusions due to inflammatory diseases (102 pg/ml; p = 0.034). Furthermore,
      hemorrhagic effusions showed significantly higher VEGF levels (1,942 pg/ml) than
      non-hemorrhagic effusions (202 pg/ml; p = 0.016) in malignant patients. In
      contrast, neither bFGF nor angiogenin were correlated with any clinical
      manifestation of pleural effusion. Immunohistochemical study revealed that
      malignant cells in the pleura were stained with anti-VEGF antibody. Our data
      suggest that VEGF secreted from tumor cells may be involved in the accumulation
      of pleural effusion in malignancy, and that increased levels of VEGF may induce
      hemorrhagic effusion.

PMID- 12187075
TI  - Balance between cell division and cell death as predictor of survival in patients
      with non-small-cell lung cancer.
AB  - OBJECTIVE: To evaluate the prognostic value of the balance between apoptosis and
      proliferation in non-small-cell lung cancer (NSCLC). METHODS: Paraffin-embedded
      sections from a consecutive series of radically resected NSCLCs were scored for
      apoptosis (in situ DNA nick end labeling assay) and proliferation
      (immunohistochemistry for MIB-1). A total of 1,000 cells were counted per case,
      to obtain apoptotic (AI) and MIB-1 indices. Other potential prognostic indicators
      (pT, pN, pStage and histology) and p53 status were also evaluated. RESULTS:
      Univariate analysis showed that adenocarcinomatous histotype (p = 0.03), nodal
      involvement (p = 0.04), higher pStage (p = 0.001) and the combination of low AI
      and high MIB-1 expression (p = 0.03) were associated with poorer outcome. The
      significant prognostic value of the combination 'low AI/high MIB-1' was also
      confirmed in a multivariate analysis after adjustment for other covariates.
      CONCLUSION: These results underline the importance of considering apoptosis and
      proliferation together to identify a subgroup of NSCLC associated with poor
      survival.

PMID- 12187076
TI  - 5'-End RET splicing: absence of variants in normal tissues and intron retention
      in pheochromocytomas.
AB  - The Ret tyrosine kinase is implicated in neuronal cell survival, kidney
      development and tumorigenesis. Several 3' and 5' transcript variants have been
      described resulting from alternative splicing of the RET pre-mRNA. The 3'
      variants code for three C-terminal isoforms, RET51, RET9 and RET43. The 5'
      variants RET2/4, RET2/5 and RET2/6 result from skipping exons 3, 3-4 and 3-5,
      respectively. These variants code for putative Ret proteins differing in their
      extracellular ligand-binding domains, and their expression is strongly regulated
      during kidney development. Here we analyzed the presence of these RET 5' variants
      in normal tissues and in MEN2 and sporadic pheochromocytomas. In all tissues
      examined, the abundance of these transcripts remained extremely low (less than 1%
      of all RET transcripts) thus indicating these species as rare variants with
      little biological meaning. On the other hand, in tumors, the 5' RET splicing
      pattern differed from that of normal tissues. Indeed, we identified a RET-derived
      transcript that results from the aberrant retention of intron 2. This transcript
      is enriched in tumor samples of both familial and sporadic origin, and indicates
      RET as a target for RNA splicing deregulation in tumor cells.

PMID- 12187077
TI  - Anti-epidermal growth factor receptor monoclonal antibody 225 upregulates
      p27(KIP1) and p15(INK4B) and induces G1 arrest in oral squamous carcinoma cell
      lines.
AB  - Epidermal growth factor receptor (EGFR) regulates the growth and progression of
      human oral squamous cell carcinoma (SCC). Recently, the link between EGFR
      signaling and the cell cycle has been identified. Some reports have described
      that EGFR-blocking monoclonal antibody 225 (mAb225) induced G1 arrest and
      inhibited the growth of various cancer cells. The purpose of this study was to
      evaluate the effect of mAb225 on human oral SCC cell lines. Exposure to mAb225 in
      culture inhibited the growth of oral SCC cell lines in an EGFR number-independent
      manner, with the percent inhibition ranging from 13.8 to 76.6%. Flow-cytometric
      analysis demonstrated that treatment with mAb225 induced cell accumulation in G1
      phase, accompanied by a decrease in the percentage of cells in the S phase.
      Apoptosis was not seen in this study. G1 arrest was accompanied by a decrease in
      CDK2-, CDK4-, and CDK6-associated histone H1 kinase activities, and an increase
      in the expression levels of cell cycle inhibitors p27(KIP1) and p15(INK4B). These
      results suggested that the antiproliferative effect of EGFR blockade by mAb225 in
      oral SCC may be mediated by p27(KIP1) and p15(INK4B).

PMID- 12187078
TI  - Methyl group deficiency States.

PMID- 12187079
TI  - Novel aspects of transforming growth factor-Beta in diabetic kidney disease.

PMID- 12187080
TI  - Josephus Andreas Jacobus Plenck - a forerunner of modern diuretic therapy.
AB  - Joseph Andreas Jacobus Plenck was born in 1735 in Vienna where he studied surgery
      with Johan Christian Retter. At age 35 he was appointed Professor of Surgery and
      Obstetrics by Maria Theresia. Subsequently he became professor and life long
      secretary of the Medical Military Academy know as the Josephinum where he worked
      up to 1807. He was one of the most brilliant scientific writers of his time. Here
      we analyze his medical treatise, Icones Plantarum Medicinalium secundum systema
      Lynnaei cum enumeratione virium et usus medici, chirurgici et diaetetici,
      published in folio in Latin and German. This is a therapy based on plants in
      which the author discusses the medical use of 758 plants. This article is
      centered on 111 plants with diuretic properties which still appear in many
      pharmacopoeias.

PMID- 12187081
TI  - A comparison between the soluble transferrin receptor, transferrin saturation and
      serum ferritin as markers of iron state in hemodialysis patients.
AB  - An adequate iron management is important in the treatment of anemia and in
      hemodialysis (HD) patients. Serum ferritin and transferrin saturation (TS) may be
      influenced by the presence of inflammation. Recently, the soluble transferrin
      receptor (s-TfR) has been advocated as a parameter of iron status in HD patients.
      The aim of the present study was to assess firstly the relation between serum
      ferritin, TS, and s-TfR in HD patients and to predict their agreement (assessed
      by kappa) in the diagnosis of iron deficiency, and, secondly, to assess the
      influence of inflammation on the relation between the parameters of iron state.
      Iron deficiency by either marker was respectively defined as ferritin <100
      microg/l, TS <20%, or s-TfR >2.4 microg/ml. In the overall group of patients, TS
      and s-TfR were significantly related (r = -0.38), whereas s-TfR and serum
      ferritin were not. Both serum ferritin and TS were related to CRP (r = 0.50 and 
      0.34; p < 0.05), whereas s-TfR was not. The kappa value for agreement between
      serum ferritin and TS in the diagnosis of iron deficiency was 0.24 (p = 0.07),
      0.12 (p = NS) for the agreement between TS and s-TfR and 0 for that between serum
      ferritin and s-TfR. In patients with CRP levels <or=2 mg/l (n = 16), the relation
      between parameters of iron state did not improve. Concluding, a large
      disagreement is observed between ferritin, TS and sTfR as markers of iron
      deficiency in HD patients, which appears to be only partly explained by the
      effect of inflammation.

PMID- 12187082
TI  - Influence of spontaneous platelet aggregation on progression of glomerular
      disease.
AB  - Platelet secretion products may play an important role in the pathogenesis and
      progression of the kidney disease. Amongst the parameters describing platelet
      hyperactivity the measurement of spontaneous platelet aggregation (SPA) seems
      particularly useful. In this study SPA as well as mean platelet volume (MPV),
      modal platelet volume (PLT Mode) and platelet count (PLT) were investigated in 60
      patients with biopsy proven primary glomerulonephritis. SPA was measured using
      the turbidimetric method according to Born with no enhancers added. Serum
      creatinine concentration (Cr), reciprocal serum creatinine concentration (1/Cr)
      and endogenous creatinine clearance (Cl(Cr)) were used for the renal function
      estimation. Protein and lipid profiles as well as coagulo-fibrinolytic balance
      were measured in parallel. The investigated group consisted of 30 non-nephrotic
      patients (CGN) - in 9, SPA was found (CGN-B) while 21 had SPA <10% (CGN-A), and
      30 nephrotic patients (CGN+NS) - 19 with SPA (CGN+NS-B) and 11 without (CGN+NS
      A). SPA was found to be a constant platelet feature in patients with chronic
      glomerulopathy. The group remained under observation for 36 months. 41 patients
      were included in the 3-year prospective study which revealed the significant
      influence of the blood platelet hyperaggregability on the renal disease
      progression. A significantly increased serum creatinine concentration, decreased
      1/Cr parameter and decreased glomerular filtration rate (Cl(Cr)) were noted in
      subgroups showing SPA. A significant correlation between SPA and (Delta)Cr/month
      (r = 0.41), (Delta)1/Cr/month (r = 0.38) as well as (Delta)Cl(Cr)/month (r =
      0.52) was found. The platelet activity and thus SPA can be altered by various
      factors: albumin and fibrinogen plasma concentrations, thrombosis activation and
      possibly lipoprotein metabolism disturbances. A characteristic feature of
      spontaneously aggregating platelet is their increased volume (MPV). CONCLUSION:
      Platelet hyperaggregation in one of nonimmunological factors stimulates the
      progression of glomerulonephritis.

PMID- 12187083
TI  - Hospitalizations for valvular heart disease in chronic dialysis patients in the
      United States.
AB  - BACKGROUND: Valvular heart disease has not been studied in a national population
      of end stage renal disease patients. METHODS: 327,993 dialysis patients in the
      United States Renal Data System initiated from 1 January 1992 to 30 June 1997
      were analyzed in a historical cohort study of patients hospitalized for valvular
      heart disease (ICD9 Code 424.x, excluding endocarditis, and 394.x-397.x).
      RESULTS: 2,778 dialysis patients were hospitalized for VHD (incidence rate, 3.57
      per 1,000 person years), and dialysis patients had an age-adjusted incidence
      ratio for valvular heart disease of 5.06 (95% confidence interval, 4.00-6.42)
      compared to the general population in 1996. In Cox regression analysis, time to
      hospitalization for valvular heart disease was associated with earlier year of
      first dialysis, increased age, congestive heart failure and use of erythropoietin
      prior to dialysis, while African-American race (AHR 0.62, 0.52-0.74) was
      associated with decreased risk of hospitalization for valvular heart disease.
      Patients hospitalized for valvular heart disease had increased mortality compared
      to all other dialysis patients (adjusted hazard ratio by Cox regression 1.35, 95%
      CI, 1.25-1.46). CONCLUSIONS: Dialysis patients were at increased risk for
      hospitalizations for valvular heart disease compared to the general population,
      which substantially decreased patient survival. The reasons for the decreased
      risk of African-Americans on chronic dialysis for this complication should be the
      subject of future trials.

PMID- 12187084
TI  - Angiotensin II type 1 receptor gene polymorphism in end-stage renal disease.
AB  - The genes of the renin-angiotensin system (RAS) are involved in progression of
      renal failure. We examined the A1166C polymorphism at the angiotensin II type 1
      (AT1R) locus in patients with end-stage renal disease (ESRD). The distribution of
      genotype and allele frequencies was compared in 430 dialysis patients and 260
      healthy controls. DNA samples were amplified by the polymerase chain reaction
      (PCR) and amplification products were digested with BsuRI restriction enzyme. In
      the presence of cytosine (C) there is a restriction site for this enzyme, giving
      a fragment of 231 bp (C allele), whereas undigested 255 bp fragment indicates the
      presence of the A allele. The higher frequency of combined AC and CC genotypes
      was observed in the patient group than in controls (48.6 vs. 39.5%, p < 0.05).
      The average time from the onset of renal disease to ESRD in patients with C
      allele was significantly shorter than in those with AA genotype (6.3 vs. 13
      years, p < 0.01). Positive family history of renal disease in patients with AC/CC
      genotype seems to increase this effect. Our results indicate that the presence of
      C allele of the AT1R locus polymorphism might be associated with faster
      deterioration of renal function.

PMID- 12187085
TI  - Usage of T cell receptor variable segments of the beta-chain in IgA nephropathy.
AB  - BACKGROUND: We previously reported that glomerulonephritis associated with
      Staphylococcus aureus infection (SAGN) showed an increased usage of T cell
      receptor Vbeta 5.3 and 8 in peripheral lymphocytes and mesangial IgA and IgG
      depositions. To elucidate the immunological mechanisms and pathogenesis of IgA
      nephropathy, we analyzed the usage of TCR Vbeta in both peripheral blood
      lymphocytes (PBLs) and renal infiltrating T cells from IgA-N patients. METHODS:
      In 38 patients with IgA nephropathy and controls, the usage of TCR Vbeta in PBLs
      were analyzed using monoclonal antibodies against Vbeta 3.1, Vbeta 5.1, Vbeta 5.2
      + 5.3, Vbeta 5.3, Vbeta 6.7, Vbeta 8, Vbeta 12.1, and Vbeta 13.1 + 13.3 with
      three-color flow cytometry. Furthermore, we examined immunohistochemically renal
      biopsy specimens using antibodies against Vbeta 5.3 and Vbeta 8. RESULTS: The
      percentages of DR+CD4+CD8- cells, CD45RO+CD4+ cells, and CD45RO+CD4+DR+ cells in
      PBLs from IgA nephropathy were significantly higher than controls. The
      percentages of TCR Vbeta 5.3 positive cells and TCR Vbeta 8 positive cells in
      PBLs from patients were 1.3 +/- 0.1 and 3.1 +/- 0.2%, and both were significantly
      higher than controls. The percentage of renal interstitial TCR Vbeta 5.3
      expression was significantly higher than that in PBLs. However, there was no
      significant difference between the TCR Vbeta 8 expression in the interstitium and
      that in PBLs. CONCLUSIONS: TCR Vbeta 5.3 and 8 usage and broad CD4+ T cell
      activation have occurred in IgA nephropathy. These changes were similar but weak
      compared with formerly reported SAGN.

PMID- 12187086
TI  - Treatment modalities and outcome of the renal victims of the Marmara earthquake.
AB  - BACKGROUND/AIMS: Treatment of renal problems during natural catastrophes is
      highly complicated both for medical and logistic reasons. The therapeutic
      interventions applied to and the outcome of 639 victims with acute renal problems
      during the catastrophic Marmara earthquake have been the subject of this study.
      METHODS: Questionnaires regarding information about 63 clinical and laboratory
      variables were sent to 35 reference hospitals that treated the victims.
      Information considering therapeutic interventions and outcome obtained through
      these questionnaires was submitted to analysis. RESULTS: At least one form of
      renal replacement therapy was administered to 477 (74.6%) of the 639 victims. Of
      these, 437, 11, and 4 were treated solely by intermittent hemodialysis,
      continuous renal replacement therapy, and peritoneal dialysis, respectively; 25
      victims needed more than one dialysis modality. In total, 5,137 hemodialysis
      sessions were performed. Also, 2,981, 2,837 and 2,594 units of blood, fresh
      frozen plasma, and human albumin were administered, respectively. Transfusion of
      these products was usually associated with higher rates of dialysis needs and
      mortality. Ninety-seven patients (15.2%) died. The mortality rate of dialyzed
      victims was higher as compared to nondialyzed ones (17.2 vs. 9.3%, p = 0.015).
      CONCLUSIONS: Massive amounts of dialysis treatment as well as blood and blood
      product transfusions can be necessary in the treatment of catastrophic earthquake
      victims with nephrological problems. Despite the potential risk of a high
      mortality, in the case of appropriate and energetic medical interventions,
      reasonable final outcomes can be achieved.

PMID- 12187087
TI  - The Decorin gene 179 allelic variant is associated with a slower progression of
      renal disease in patients with type 1 diabetes.
AB  - Background genetic factors may influence the variability in the rate of
      progression of kidney disease in type 1 diabetes. In diabetes, progressive
      mesangial matrix expansion and glomerular sclerosis are, to a large extent,
      mediated by TGF-beta1. Decorin, a proteoglycan which is a component of the
      extracellular matrix, regulates TGF-beta1 activity and expression. We have
      examined the relationship between the 179/183/185 polymorphism of the Decorin
      gene and the progression of diabetic nephropathy. METHODS: From a cohort of 175
      European patients with diabetic nephropathy, we studied 79 patients who were
      selected because they had a follow-up of at least 2 years (average 6.5 years;
      range: 2.5-15 years), and regular measurements of serum creatinine on 5 or more
      occasions. Creatinine clearance (CrCl) calculated from serum creatinine
      concentration was used as a measure of derived glomerular filtration rate (dGFR).
      All patients were on antihypertensive therapy. RESULTS: The rate of dGFR decline
      in the whole cohort was [median (range)] 4.6 (-3.8 to 18) ml/min/year. No patient
      with 185 allele was found. Patients with 179/183 and 179/179 genotype (n = 14),
      who were considered together and named 179 carriers, had a slower rate of GFR
      decline [2.1 (0.06-11.7) ml/min/year] as compared to patients with Decorin
      183/183 genotype (n = 65) [5.6 (-3.8 to 18) ml/min/year; p < 0.001]. In addition,
      when considering individual data, patients carrying the 179 allele had a 3.0
      (95%CI: 1.8-4.2)-fold higher probability to be slow progressors (i.e. GFR decline
      below the median). This difference could not be accounted for by differences in
      duration of disease, type and duration of antihypertensive therapy, albumin
      excretion rate, blood glucose or blood pressure control. In a multivariate
      logistic analysis albumin excretion rate (p < 0.001), mean arterial pressure (p =
      0.07) and Decorin gene polymorphism (p = 0.036), but not HbA1c, were
      independently correlated with the rate of dGFR fall. CONCLUSION: The 179 allele
      variant of the Decorin gene is related to a slower progression of DN in type 1
      diabetic patients with albuminuria and receiving antihypertensive therapy.

PMID- 12187089
TI  - The negative Ca(2+) balance is involved in the stimulation of PTH secretion.
AB  - The low calcium (Ca(2+)) dialysate have been developed to diminish the risk of
      hypercalcemia with the administration of active vitamin D and Ca(2+) carbonate as
      phosphate binder. Today, increasing numbers of hemodialysis (HD) patients have
      been on the low Ca(2+) dialysate (Ca(2+) = 2.5 mEq/l). However, the clinical
      consequences of a negative calcium net-balance which may be induced by the use of
      low Ca dialysate are not well evaluated. In the present study, we explored the
      effects of low Ca(2+) dialysate on the calcium balance and the PTH secretion.
      Eighty one chronic HD patients (male/female: 47/34; mean age: 60.2 +/- 1.5 years;
      mean HD periods: 11.1 +/- 0.8 years) who had been dialyzed with 3.0 mEq/l Ca(2+)
      dialysate were studied. All patients were transferred to the low Ca dialysate,
      which actually brought about a negative net-balance in Ca (mean: -94.5 mg) and an
      increase in serum intact PTH levels (mean: +23.7%: p = 0.03) during a single HD
      session. However, no changes in serum ionized Ca(2+) were found in spite of
      negative Ca(2+) balance. One month after change to the low Ca(2+) dialysate
      (total 12 sessions in each case), serum intact PTH levels increased significantly
      (186.7 +/- 19.5 vs. 216.2 +/- 21.9 pg/ml: p = 0.01) in spite of the fact that no
      changes were found in serum ionized Ca(2+), Pi and Mg. This result indicates that
      the negative Ca(2+) balance during low-Ca(2+) hemodialysis-stimulated PTH
      secretion, which offset the decrease of serum Ca(2+); a trade-off phenomenon
      between negative Ca balance and PTH. This suggests that low Ca(2+) dialysate may
      exaggerate the progression of secondary hyperparathyroidism.

PMID- 12187088
TI  - Blood sugar control reverses the increase in urinary excretion of prostaglandin D
      synthase in diabetic patients.
AB  - BACKGROUND/AIMS: We investigated basal levels of serum and urinary lipocalin-type
      prostaglandin D synthase/beta-trace (L-PGDS) in type-2 diabetic patients and
      explored whether glycemic control affects L-PGDS status in another 55 diabetic
      inpatients with normoalbuminuria. METHODS: Fifty-five type-2 diabetic outpatients
      (HbA1c, 9.14 +/- 0.20%; creatinine (Cr), 85.1 +/- 2.4 micromol/l), and 55 age
      matched healthy control subjects were recruited. Serum and urinary levels of L
      PGDS were determined with respect to the stage of diabetic nephropathy. The L
      PGDS was localized by immunohistochemistry. RESULTS: The urinary L-PGDS index
      increased in diabetic patients, compared with the controls (234.8 +/- 27.4 vs.
      73.8 +/- 7.8 microg/mmol Cr, p < 0.001). Even in normoalbuminuric patients as
      well as in microalbuminuric patients, urinary L-PGDS indexes were higher than the
      controls (166.0 +/- 21.1, p < 0.0001 and 338.6 +/- 62.5 microg/mmol Cr, p <
      0.0001, respectively), although the serum L-PGDS level was equal to that in the
      control subjects. Multiple regression analysis revealed that the urinary L-PGDS
      index was predicted solely by glucose levels and type-IV collagen index, whereas
      the serum L-PGDS was determined mainly by age and serum Cr. Glycemic control
      reduced the urinary L-PGDS index towards the normal range in diabetic patients
      with normoalbuminuria (172.3 +/- 6.6 vs. 118.1 +/- 2.6 (SE) microg/mmol Cr, p <
      0.0001). Immunohistochemistry showed that L-PGDS was uniquely present in the
      renal tubules in diabetes while in nondiabetics, L-PGDS occurred solely in the
      peritubular interstitium, not in the tubular cells. CONCLUSION: Inadequate
      glycemic control is responsible for urinary L-PGDS excretion in the diabetic
      patients. Urinary L-PGDS is useful to predict subclinical renal injury associated
      with type-2 diabetes.

PMID- 12187090
TI  - Adjusting dry weight by extracellular volume and body composition in hemodialysis
      patients.
AB  - BACKGROUND: At present, the determination of dry weight in patients on
      hemodialysis is largely made empirically by trial and error. Extracellular volume
      (ECV) assessment by bioimpedance analysis (BIA) is a preferable technique for
      determining dry weight, and it also provides useful data on body composition.
      METHODS: We measured the ECV of 74 normal subjects and 121 stable chronic
      hemodialysis patients postdialysis. In addition, for the dialysis patients, we
      measured intracellular volume (ICV) and lean body mass (LBM) by BIA, and analyzed
      the ECV, blood pressure and complications of dialysis. We adjusted dry weight
      according to the ECV and repeated a BIA exam 4 months later to evaluate changes
      in body composition, blood pressure and dialysis status of these patients.
      RESULTS: The ECV as a percentage of weight (ECV%) of hypertensive patients was
      significantly higher than that of normotensive patients (24.29 +/- 3.56% vs.
      21.50 +/- 2.38%, p < 0.001). All patients with excessive ECV% had hypertension,
      but not all hypertensive patients had excessive ECV%. None of the normotensive
      patients had ECV excess. Some hypertensive patients with symptoms of dialysis
      complications still had excessive ECV%. Eight hypertensive patients with
      excessive ECV had decreased dry weight. ECV% (29.80 +/- 2.03% vs. 27.10 +/-
      2.99%, p < 0.001) and blood pressure (159 +/- 7 / 97 +/- 4 vs. 137 +/- 10 / 86 +/
      8 mm Hg, p = 0.006 for systolic and p = 0.004 for diastolic) decreased. ECV was
      the only portion of body composition that decreased (p < 0.001) after decreasing
      dry weight, the other parameters remaining unchanged. Twenty symptomatic
      normotensive patients improved with elevation of the dry weight. The ECV (p =
      0.007), ICV (p = 0.009) and LBM (p < 0.001) were significantly increased after
      increasing dry weight, while the ECV% (p = 0.39) and fat (p = 0.46) remained
      unchanged. CONCLUSIONS: (1) For hypertensive patients, ECV must be evaluated in
      order to adjust dry weight and correct hypertension. (2) For normotensive
      patients, if dialysis complications occur, dry weight should be increased until
      symptoms disappear or the blood pressure begins to rise.

PMID- 12187091
TI  - Assessment of haemostatic risk factors in patients with acute renal failure
      associated with severe systemic inflammatory response syndrome. Development of a
      prognostic index.
AB  - BACKGROUND/AIM: The prognosis of acute renal failure (ARF) in the Intensive Care
      Unit (ICU) is variable and depends mainly on the underlying disease.
      Consequently, the outcome prediction is difficult. The majority of the prognostic
      measures used include clinical parameters and routine laboratory tests but not no
      study has considered the prognostic value of haemostatic disturbances. These
      disturbances play a key role in the evolution of multiple organ dysfunction
      syndrome (MODS) in patients with ARF, which occurs as part of systemic
      inflammatory response syndrome (SIRS). The aim of the present study was to search
      for early significant predictive factors among a group of haemostatic parameters
      in these patients. METHODS: Forty patients (age: 60.1 +/- 14.1 years) with ARF
      (requiring renal replacement therapy) associated with SIRS and haemodynamic
      instability (systolic blood pressure <90 mm Hg and/or vasopressor drugs) were
      included. The plasmatic levels of the following haemostatic factors were measured
      within the first 6 h of the SIRS evolution: von Willebrand Factor (vWF),
      thrombomodulin, plasminogen activity inhibitor type 1 (PAI-1 antigen), tissue
      type plasminogen activator (t-PA antigen), prothrombin fragment 1 + 2 (F1 + 2),
      thrombin-antithrombin complexes (TAT) and D-dimer. Age, sex, medical or surgical
      disease, septic status or not, type of ARF (prerenal or acute tubular necrosis,
      oliguric or nonoliguric), and requirement for inotropics and mechanical
      ventilation were also considered. Univariate and multivariate logistic
      regressions were used to identify the risk factors for death and to develop a
      possible mortality prediction model on this basis. RESULTS: By univariate
      analysis, high levels of PAI-1 antigen (>or=60 ng/ml) and F1 + 2 (>2.5 nmol/l) at
      early phases of ARF-severe SIRS were found to be independent risk factors for
      death (odds ratio (OR) = 6.37, p = 0.0181 and OR = 5.49, p = 0.0238,
      respectively). Age over 61 years and requirement of mechanical ventilation were
      independent death risk factors (OR = 4.33, p = 0.0251 and OR = 2.4, p = 0.0078,
      respectively). A possible mortality prediction model was obtained including the
      age and the PAI-1 antigen and F1 + 2 variables. CONCLUSION: In patients with ARF
      associated with severe SIRS, the independent risk factors from the early phases
      of the process are not only the known variables such as advanced age, but also
      high levels of PAI-1 antigen and F1 + 2. In the future, the individual
      probability of death could be calculated by a prediction model which includes
      these variables.

PMID- 12187092
TI  - Renoprotection following treatment of secondary hyperparathyroidism with
      percutaneous ethanol injection in pre-dialysis patients.
AB  - What could be done for patients with chronic renal failure are marginally
      beneficial. Among 58 pre-dialysis patients, we found 24 of chronic
      glomerulonephritis (CGN) with serum creatinine >5 mg/dl and intact parathyroid
      hormone (i-PTH) >200 pg/ml. In this study, we determined if the residual renal
      function could be preserved when hyperparathyroidism was corrected by either low
      dose calcitriol treatment or ethanol injection. The 58 CGN patients were divided
      into three groups. The first group, which comprised 11 cases with i-PTH >200
      pg/ml and had parathyroid mass, were treated by ultrasonography-guided
      percutaneous ethanol injection therapy (PEIT). The second study group composed of
      13 cases with i-PTH >200 pg/ml without parathyroid mass were treated by
      calcitriol 1 microg every other day. The third group made up of 34 cases with i
      PTH <200 pg/ml, who did not receive calcitriol or ethanol therapy. All patients
      were followed up within 2 years or until dialysis. The average rate of decline in
      renal function (slope of reciprocal serum creatinine vs. time) was 0.0025 +/-
      0.0026 dl/mg month in group 1, 0.0054 +/- 0.0024 in group 2, and 0.0067 +/-
      0.0025 in group 3 (p = 0.018 in group 1 vs. group 2, p < 0.001 in group 1 vs.
      group 3). The declines of i-PTH, phosphorus, and alkaline phosphatase, and the
      increase of calcium were all significantly different between group 1 and group 3.
      Two cases of group 1, 6 cases of group 2, and 20 cases of group 3 entered into
      dialysis during this study. In conclusion, selective PEIT guided by color Doppler
      flow mapping is an effective therapy for treating hyperparathyroidism and
      protecting the residual renal function.

PMID- 12187093
TI  - Renal transplantation of highly sensitised patients via prioritised renal
      allocation programs. Shorter waiting time and above-average graft survival.
AB  - BACKGROUND: Highly sensitised renal transplant candidates (HSP) have a reduced
      chance of receiving a transplant. In Eurotransplant (ET), two special allocation
      programs have been made available for such patients: the Highly Immunised Tray
      (HIT) program and the Acceptable Mismatch program (AM), albeit with different
      inclusion and exclusion criteria (HIT, current PRA% >or=85%; AM, current and/or
      historical PRA% >or=85%). When a suitable kidney is available for a patient,
      included in these special programs, the kidney is mandatory offered. In contrast,
      in the point score system of the standard ET kidney allocation procedure (ETKAS),
      HSP (PRA >or=85%) only get a marginal bonus according to their current
      sensitisation. It was tested whether the allocation priority of the two special
      allocation programs is justified from the perspective of transplant outcome.
      METHODS: The post- transplant outcomes of recent consecutive cohorts of AM, HIT
      and HSP-ETKAS transplants were compared. The end points were initial graft
      function, rejection episodes during the first three months post-transplant, and 1
      year kidney graft outcome. RESULTS: Between January 1, 1997 and June 30, 1998,
      101 HSP received a kidney-only transplant: 29 via AM, 39 via HIT and 33 via
      ETKAS. HLA-A,B,DR matching was more favourable in the AM and HIT allocation
      groups and their waiting times till transplantation were much shorter than those
      of the HSP-ETKAS allocation group. The incidence of initial graft non-function
      was similar among the three HSP allocation groups, averaging 50%. Recovery of the
      initial non-function was more likely for AM and HIT transplants. No difference
      was present with regard to the percentage of patients who experienced at least
      one rejection episode during the first three months post-transplant, averaging
      43%. However, the AM group had less severe and/or less recurrent rejection
      episodes. The 1-year kidney graft survival, censored for death with functional
      graft, was 96% for AM, 82% for HIT and 75% for HSP-ETKAS transplants (p = 0.04).
      CONCLUSIONS: The two special allocation programs for HSP do yield adequate
      results and offer a shorter waiting time, compared to the standard kidney
      allocation procedure. The AM approach might be preferred because of the smoother
      post-transplant management and the better graft survival, keeping the HIT
      approach as a back up. Since the allocation priority is justified in view of
      efficiency, the renal transplant community should support the incorporation of a
      special allocation program for HSP in their respective organ exchange program.

PMID- 12187094
TI  - The common mutations C677T and A1298C in the human methylenetetrahydrofolate
      reductase gene are associated with hyperhomocysteinemia and cardiovascular
      disease in hemodialysis patients.
AB  - BACKGROUND: Plasma total homocysteine (tHcy) level might be an important risk
      factor for the development of cardiovascular disease (CVD) in dialysis patients.
      While both renal failure and mutations of the 5,10-methylenetetrahydrofolate
      reductase (MTHFR) gene may result in hyperhomocysteinemia and CVD, the distinct
      roles of the thermolabile MTHFR mutation at nucleotide C677T and the more
      recently described mutation at nucleotide A1298C have not been evaluated
      concurrently in patients on hemodialysis. METHODS: A cross-sectional study was
      performed in 120 maintenance HD patients to determine the prevalence of MTHFR
      C677T and A1298C mutations and their relative association to hyperhomocysteinemia
      and CVD. RESULTS: Both mutations, the C677T and the A1298C, were highly prevalent
      in HD patients with allele frequencies of 0.41 and 0.27, respectively. The
      prevalence of CVD in HD patients was 55% and its significant risk factors
      included, in descending order, hyperhomocysteinemia, MTHFR C677T mutation, low
      serum folate levels, diabetes mellitus, hypertension, and double heterozygote
      state for both MTHFR mutations (677CT/1298AC). MTHFR A1298C mutation alone and
      gender were not associated with either hyperhomocysteinemia or increased CVD
      risk, but the HD patients with homozygotes 1298CC and wild alleles 677CC
      (677CC/1298CC) have significant increase of tHcy (37.7 +/- 12) and high
      prevalence of CVD. CONCLUSIONS: Hyperhomocysteinemia, serum folate levels and
      both C677T and A1298C MTHFR mutations are associated with CVD in HD patients.

PMID- 12187095
TI  - Insomnia in diabetic hemodialysis patients. Prevalence and risk factors by a
      multicenter study.
AB  - BACKGROUND: Insomnia is one of the most common problems in dialysis patients, and
      likely to contribute impairment in quality of life, which has a positive
      correlation with patients' survival. In diabetic patients, morbidity and
      mortality are substantially higher than in the nondiabetic counterparts, and also
      the incidence of sleep disturbances. However, there is no means to predict sleep
      disturbance in the dialysis patients especially in diabetics. To define the
      prevalence and risk factors for insomnia in diabetic patients on hemodialysis, we
      undertook a cross-sectional multicenter study. METHODS: Eighty-two diabetic
      patients (50 men/32 women, aged 58.7 +/- 9.23 years) on maintenance hemodialysis
      for more than 6 months from 12 different hospitals were enrolled. The demographic
      data, subjective symptoms, depression scale, and insomnia were assessed by
      questionnaires, and lean body mass, BMI, Kt/V, subjective global assessment,
      nursing assessment score (NAS), and biochemical parameters were examined.
      RESULTS: The number of patients with and without insomnia were 56 and 26,
      respectively, which amounted to 68.2% for insomnia. NAS (28.1 +/- 3.81 vs. 30.8
      +/- 2.88, p = 0.002), serum albumin concentration (3.82 +/- 0.44 vs. 4.09 +/-
      0.36 g/dl, p = 0.008), and depression scale (25.2 +/- 12.1 vs. 18.9 +/- 10.3, p =
      0.025) were significantly different between them. Patients with insomnia were
      older (60.5 +/- 9.0 vs. 56. 1 +/- 9.60 years, p = 0.053) and felt pain (38.5 vs.
      15.3%, p = 0.06) more frequently than those without insomnia. The scale of
      depression was correlated with NAS (r = -0.455, p < 0.001) and the serum albumin
      concentration was correlated with NAS (r = 0.337, p = 0.002). NAS, age, and serum
      albumin concentration were the major risk factors for insomnia in logistic
      regression analysis. CONCLUSION: The prevalence of insomnia in diabetic
      hemodialysis patients was 68.2%. Age, nutritional status, and depression were the
      major risk factors for sleep disturbance in diabetic patients.

PMID- 12187096
TI  - Potential of sanguiin H-6 against oxidative damage in renal mitochondria and
      apoptosis mediated by peroxynitrite in vivo.
AB  - Potential of sanguiin H-6, a component of Sanguisorbae Radix, to protect against
      oxidative damage in renal mitochondria and apoptosis mediated by peroxynitrite
      (ONOO(-)) was examined using a model in which rats were injected with
      lipopolysaccharide (LPS) and then subjected to renal ischemia followed
      reperfusion (LPS plus ischemia-reperfusion). Ischemia-reperfusion was achieved by
      occluding bilateral renal artery for 60 min and then releasing for 350 min. At 50
      min after ischemia started, LPS was injected intravenously. LPS plus ischemia
      reperfusion induced a large amount of 3-nitrotyrosine, an oxidative product of
      protein that is produced via ONOO(-) nitration, which was not detectable in
      normal group. Oxidative damage of mitochondria was indicated by an accumulated
      thiobarbituric acid (TBA)-reactive substance, glutathione (GSH) depletion and
      glutathione peroxidase (GSH-Px) inactivation in the mitochondria. Treatment of
      rats with sanguiin H-6 (10 mg/kg body weight/day) for 30 days prior to LPS plus
      ischemia-reperfusion attenuated the oxidative damage in the mitochondria. The
      amount of TBA-reactive substance was decreased and the GSH levels significantly
      increased as compared with that in control group. However, its effect on GSH-Px
      activity was much weaker. Apoptosis induced by LPS plus ischemia-reperfusion was
      detected by fluorescence staining, TdT-mediated dUTP-biotin nick end labeling and
      electrophoretic analysis. Sanguiin H-6 appeared to inhibit apoptosis, and this
      was associated with the suppression of caspase-3 activity. These beneficial
      effects of sanguiin H-6 against oxidative damage in mitochondria and apoptosis
      contributed to the improvement in renal function by reversing the elevated levels
      of blood urea nitrogen and creatinine caused by ONOO(-).

PMID- 12187097
TI  - Mesothelial dysplastic changes and lipid peroxidation induced by 7.5% icodextrin.
AB  - BACKGROUND: The issue of icodextrin biocompatibility is somehow ambiguous.
      Whereas some experimental data point at better bicompatibility of icodextrin
      compared with high glucose concentration fluid, other reports showed substantial
      cytotoxic effects upon monocytes and cultured mesothelial cells. The present
      investigation exposes the first attempt to investigate the biocompatibility issue
      in an in vivo and in situ setup. METHODS: Mice were intraperitoneally injected
      once a day with the 7.5% icodextrin solution, during 30 consecutive days.
      Imprints of the mesothelial monolayer covering the anterior liver surface were
      taken after 2 h, 15 and 30 injections, as well as after recovery periods of 7, 30
      and 60 days. Changes on the cell population were evaluated as a function of:
      density, cell surface area, cell radius, nuclear surface area, number of nucleoli
      per nucleus, nuclear cytoplasmic index, as well as for prevalence of
      multinucleation, mitosis, non-viable cells and apoptotic bodies. Additionally,
      peritoneal dialysis was performed in 3 groups of rats exposed to 4.25% glucose
      dialysis fluid, 1.1% amino acids solution, or to 7.5% icodextrin. Samples were
      taken for thiobarbituric acid reactive substances (TBARS) from each group.
      RESULTS: Mesothelial cell populations of mice exposed to 7.5% icodextrin
      displayed significantly reduced density, increased cell size, higher increased
      nuclear/cytoplasmic index, increased numbers of heterogeneous nucleoli, extremely
      low prevalence of mitosis, atypical mitosis, micronuclei, reduced cell viability
      as well as a significantly higher prevalence of apoptosis. Rats exposed to the
      same experimental solution showed significantly higher levels of TBARS (basically
      malondialdehyde), testifying for an undergoing process of lipid peroxidation.
      CONCLUSIONS: Overall, these results suggest that the 7.5% icodextrin dialysis
      solution induced, through a mechanism of lipid peroxidation, substantial DNA
      injury, leading the exposed monolayer to commit protective cellular suicide.
      Consequently, this information raises some doubts about the safety of 7.5%
      icodextrin solution in peritoneal dialysis patients.

PMID- 12187098
TI  - Exogenous albumin peptides influence the processing of albumin during renal
      passage.
AB  - Exogenous albumin peptides influence the processing of albumin during renal
      passage. BACKGROUND/AIMS: This study investigates the hypothesis that there will
      be peptide regions in albumin that will effectively compete for the receptors
      associated with the renal processing of albumin. METHODS: We employ albumin
      peptides prepared from albumin by trypsin digestion. The presentation of the
      exogenous peptides along with intact [(3)H]albumin to the kidney was made by
      intravenous injection into rats. The excretion rate and integrity of urinary
      [(3)H]albumin was measured. Similar experiments were performed with the use of
      gelatin peptides produced by trypsin digestion as controls. The formation of
      [(3)H]albumin derived fragments by extrarenal sources was also examined in rats
      with nonfiltering kidneys. RESULTS: In the presence of exogenous albumin-derived
      peptides there was a significant increase in the proportion of larger
      [(3)H]albumin fragments in the urine. This is a reversible effect. There was no
      significant change when gelatin peptides were used. The albumin peptides also
      increase the fractional clearance of [(3)H]albumin. There were no [(3)H]albumin
      derived fragments produced in plasma over a 4-hour circulation period in rats
      with nonfiltering kidneys. CONCLUSIONS: This study demonstrates that albumin
      fragments, which are produced by the kidney and not by extrarenal sources, are
      exclusively excreted in the urine. Exogenous albumin peptides were able to
      specifically exert a competitive effect on the renal enzyme cleavage of intact
      albumin.

PMID- 12187099
TI  - MCP-1 and RANTES are expressed in renal cortex of rats chronically treated with
      nitric oxide synthase inhibitor. Involvement in macrophage and monocyte
      recruitment.
AB  - Long-term inhibition of nitric oxide synthase (NOS) in rats is known to cause
      systemic hypertension and renal parenchymal injury. We have previously reported
      that activation of intra-renal renin-angiotensin system was a major contributing
      factor for renal injury in chronically NOS-inhibited rats. Massive interstitial
      infiltration of monocytes/macrophages (M/M) was characteristically seen in this
      model. The present study was performed to elucidate the role of chemokines,
      RANTES and MCP-1, in promoting M/M recruitment into the renal cortex. The number
      of infiltrating ED-1-positive cells was examined in association with the level of
      expression of RANTES and MCP1 mRNAs in the renal cortex of rats treated orally
      for 12 weeks with L-NAME. Compared to controls rats, the number of infiltrating
      ED-1-positive cells was significantly higher in L-NAME-treated rats. The mRNA
      expressions of both RANTES and MCP-1 were significantly higher in L-NAME-treated
      rats than the control. In L-NAME-treated rats, the high number of ED-1-positive
      cells and increased expression of both RANTES and MCP-1 were suppressed by ACE
      inhibitor, but not by hydralazine. In contrast, neither ED-1 counts nor RANTES
      mRNA expression were affected by angiotensin (Ang) II type 1 receptor antagonist.
      These results suggest the likely involvement of RANTES and MCP-1 in the
      recruitment of M/M into the renal cortex of rats with chronic NOS inhibition.
      Furthermore, it is also indicated that Ang II stimulates MCP-1 expression via Ang
      II type 1 receptor, whereas RANTES expression is mediated via Ang II type 2
      receptor.

PMID- 12187101
TI  - Distinct role of intrarenal cyclooxygenase-1/2 in chronic unilateral renal
      ischemia.
AB  - AIMS: The role of cyclooxygenase (COX)-1/2-induced prostaglandins (PG) in
      unilateral chronic renal ischemia of anesthetized dogs was examined. METHODS:
      Ischemic kidneys were established by reducing renal blood flow of left renal
      artery to 10% of baseline with an adjustable clip. After 4 weeks, changes in
      intrarenal contents of PGE2/PGI2 and angiotensin (Ang) II were evaluated with
      renal microdialysis and biopsy. Furthermore, the effect of a non-specific COX
      inhibitor (sulpyrine), a COX-2-specific inhibitor (NS398), and an Ang receptor
      antagonist (CS866) on renal function and renal PG contents were evaluated.
      RESULTS: Unilateral renal artery clipping reduced renal plasma flow (RPF) in
      clipped (from 59 +/- 2 to 17 +/- 1 ml/min, n = 18) and nonclipped kidneys (from
      59 +/- 2 to 44 +/- 2 ml/min) and natriuresis. Intrarenal PGE2 increased only in
      clipped kidneys (from 114 +/- 7 to 375 +/- 25 pg/ml), whereas 6-keto-PGF1alpha
      increased in both kidneys. Sulpyrine reduced intrarenal PG contents, and
      decreased RPF, GFR, and urinary sodium excretion (UNaV), whereas NS398 reduced
      UNaV in clipped (from 4.0 +/- 0.9 to 1.7 +/- 0.2 microEq/min) and nonclipped
      kidneys (from 5.4 +/- 0.5 to 2.9 +/- 0.3 microEq/min), without affecting renal
      hemodynamics. Intrarenal Ang II contents increased in clipped (from 0.70 +/- 0.06
      to 2.32 +/- 0.33 pg/mg, n = 18) and nonclipped kidneys (from 0.65 +/- 0.06 to
      2.45 +/- 0.33 pg/mg, n = 18), and CS866 improved renal hemodynamics and
      natriuresis. The elevated intrarenal Ang II content was suppressed by NS398 only
      in clipped kidneys. CONCLUSION: Unilateral renal ischemia elevates intrarenal
      PGE2 contents in clipped kidneys, which serves to countervail the aggravation of
      renal function. Furthermore, intrarenal COX isoforms may play differential roles,
      with COX-1 participating in modulation of renal hemodynamics, and COX-2
      contributing to sodium excretion and Ang II formation.

PMID- 12187100
TI  - Peritoneal transport after long-term exposure to Icodextrin in rats.
AB  - BACKGROUND: Icodextrin, an effective osmotic substance that has been proposed as
      an alternative agent for peritoneal dialysis induces ultrafiltration over long
      dwells. This study examines the peritoneal transport after exposure to Icodextrin
      in rats. METHODS: Animals were divided in 4 groups and injected daily for 30 days
      with Icodextrin 7.5 % (n = 14), Glucose 4.25 % (n = 19) or glucose 4.25% plus
      Icodextrin 7.5 % (n = 13). Rats of the control group (n = 15) were not exposed. A
      4-hour permeability study was performed using glucose at days 1, 30 and 60. At
      days 2, 31 and 61 the same animals were injected with Icodextrin. RESULTS: Slopes
      of effluent sodium at day 30 were significantly higher (p < 0.001) in the glucose
      (0.006 +/- 0.016), Icodextrin (0.013 +/- 0.014) and mixed groups (0.012 +/-
      0.017) than in the control group (-0.041 +/- 0.021). Urea D/P ratio was not
      significantly different in the 4 groups. After 30 days, glucose effluent levels
      were significantly lower (p < 0.001) in the glucose (701 +/- 278 mg/dl),
      Icodextrin (552 +/- 209 mg/dl) and mixed groups (587 +/- 344 mg/dl) than in
      control rats (1519 +/- 413 mg/dl). Effluent protein (mg/l) in the mixed group
      (1,555 +/- 357) was significantly higher (p < 0.001) than control (376 +/- 33),
      glucose (1,015 +/- 232) and Icodextrin (765 +/- 75) groups at day 30. CONCLUSION:
      The long-term use of Icodextrin does not affect small molecule transport, but
      induces changes in the peritoneal protein excretion, especially when Icodextrin
      and glucose are injected together.

PMID- 12187102
TI  - Interleukin-6 stimulates tubular regeneration in rats with glycerol-induced acute
      renal failure.
AB  - Interleukin-6 stimulates tubular regeneration in rats with glycerol-induced acute
      renal failure. BACKGROUND: Interleukin 6 (IL-6) is a pleiotropic cytokine
      released after endotoxemia, trauma and organ injury. IL-6 may act in cellular
      proliferation activating transduction signals and Ras/Map cascade or the HGF/c
      met axis. We tested the effect of IL-6 in the regeneration of tubular epithelia
      after acute tubular necrosis (ATN) in rats. METHODS: Rats with glycerol-induced
      acute renal failure (Gly-ARF) were treated with IL-6 200 microg/kg/day.
      Functional, histological and immunohistochemical tests were done 24 and 72 h
      after Gly-ARF to localise mitotic cells (BrdU). The renal expression of c-met
      (Western-Blot) and circulating levels of HGF (ELISA) were also determined.
      RESULTS: Rats with Gly-ARF had reduced creatinine clearance that was not
      influenced by IL-6. The histological appearance of ATN was also unaffected by IL
      6. The IL-6 treated rats showed a significant increase in tubular cell
      proliferation in cortex and medulla, as well as in the expression of c-met
      protein in the renal cortex, compared to untreated Gly-ARF rats. The plasma HGF
      concentration was equally elevated in treated and untreated Gly-ARF rats.
      DISCUSSION: IL-6 stimulates tubular regeneration after Gly-ARF and increases the
      expression of c-met in the renal cortex. Gly-ARF rats have high circulating
      levels of HGF that is targeted to act in the injured kidneys by the IL-6
      overexpressed renal c-met.

PMID- 12187103
TI  - Acute interstitial nephritis associated with the use of mesalazine in
      inflammatory bowel disease.
AB  - BACKGROUND: In the last 10 years several reports have linked oral 5
      aminosalicylic acid (5-ASA) therapy to acute and chronic tubulointerstitial
      nephritis, but to our knowledge only 2 patients have been reported with terminal
      end-stage renal disease due to mesalazine (5-ASA). After 1 year of treatment with
      5-ASA annual monitoring of serum creatinine is recommended. RESULTS: We report
      the development of end-stage renal disease in a patient 10 months after the last
      assessment of serum creatinine, which was normal at 71 micromol/l. CONCLUSION:
      Because of this dangerous side effect, we would like to recommend 6-monthly
      assessment of renal function.

PMID- 12187104
TI  - Mechanisms and kinetics of Bowman's epithelial-myofibroblast transdifferentiation
      in the formation of glomerular crescents.
AB  - BACKGROUND: We investigated the mechanisms and kinetics of Bowman's epithelial
      myofibroblast transdifferentiation in the formation of glomerular crescents.
      METHODS: Crescentic glomerulonephritis was induced by i.v. injection of rabbit
      anti-rat glomerular basement membrane antiserum in WKY rats. RESULTS: Cellular
      crescents (83.5% of glomeruli) were first observed at day 7 after disease
      induction. Immunostaining of alpha-smooth muscle actin (alpha-SMA), as a marker
      for the myofibroblast phenotype, was found in some periglomerular regions as
      early as day 3, when it was also seen in parietal epithelial cells (PEC) of
      Bowman's capsule at day 5 and in crescent formation at day 7. Proliferation
      marker Ki67-positive PEC was found at day 3, and double Ki67- and alpha-SMA
      positive PEC could be seen at day 5. The migratory figure of PEC with the
      expression of alpha-SMA was found by immunoelectron microscopy. At day 7, some
      crescent cells were stained positive for PEC marker, protein gene product 9.5, in
      association with alpha-SMA or Ki67. Expression of transforming growth factor
      (TGF)-beta receptor types I and II, as well as platelet-derived growth factor
      (PDGF) receptor beta and PDGF-B increased in PEC as early as day 3. At day 5
      marked deposition of cellular and common fibronectin, but not other extracellular
      matrix components examined was found in Bowman's spaces where ED 1-positive
      macrophages infiltrated. CONCLUSIONS: PEC may be stimulated to proliferate and/or
      transdifferentiate into myofibroblast phenotype possibly by action of TGF-beta
      and PDGF and/or binding of fibronectin to PEC, then migrate and/or proliferate,
      participating in glomerular crescents.

PMID- 12187105
TI  - Acute focal bacterial nephritis: report of four cases.
AB  - Focal acute bacterial nephritis is a localized bacterial infection of the kidney
      presenting as an inflammatory mass not containing drainable pus. The further
      distinction between acute focal bacterial nephritis and other renal masses is
      aided by the appropriate use of renal sonography and computed tomography. We
      report 4 cases with this entity.

PMID- 12187106
TI  - Effect of polyamines on mesangial cell ecto-5'-nucleotidase and ecto-ATPase
      activity.
AB  - Polyamines were found to modulate the activity of several membrane-bound enzymes,
      participating in cell growth and differentiation. We have studied the effect of
      polyamines (spermidine, spermine and putrescine) on rat mesangial cell
      ectoenzymes: 5'-nucleotidase, Mg(2+)-ATPase and Ca(2+)-ATPase. Ecto-5'
      nucleotidase activity was significantly increased after 48 h treatment with
      spermine and spermidine. Mg(2+)-ATPase was increased only after treatment with
      spermidine; however, Ca(2+)-ATPase was significantly increased after both
      spermine and spermidine treatment of mesangial cells. Culture of mesangial cells
      with putrescine did not change the activity of these ectoenzymes. Increased
      expression of mesangial cell ecto-ATPase and ecto-5'-nucleotidase after spermine
      and spermidine treatment could result in an increased production of adenosine, a
      powerful autacoid interesting with respect to a role of mesangial cells in
      inflammatory processes.

PMID- 12187107
TI  - Increased expression of glomerular mesangial cell 5'-nucleotidase in membranous
      nephropathy.
AB  - It has been demonstrated in anti-Thy1 glomerulonephritis that extracellular
      adenine nucleotides have a significant pro-inflammatory activity, however,
      glomerular ATP/ADPase, which in concert with 5'-nucleotidase converts ATP/ADP,
      and AMP to anti-inflammatory adenosine had an anti-inflammatory role. We have
      studied distribution of 5'-nucleotidase and divalent cation-activated ATPase in
      kidney biopsies of 15 patients with glomerulonephritis. The major finding was an
      overexpression of 5'-nucleotidase in the mesangium of kidney from patients with
      membranous nephropathy. No change in 5'-nucleotidase expression was observed in
      other common forms of glomerulonephritis: IgA nephropathy, mesangioproliferative
      and mesangiocapillary glomerulonephritis. The distribution of Mg(2+)-ATPase in
      investigated specimens was similar to control distribution. Results obtained in
      this study indicate increased mesangial expression of 5'-nucleotidase in non
      proliferative form of glomerulonephritis consistent to a role of mesangial cells
      in inflammatory processes.

PMID- 12187108
TI  - Renal tubular dysfunction in a patient with beta-thalassemia minor.
AB  - Beta-thalassemia minor is a hemoglobinopathy which has been known as a
      symptomless carrier state. Although there are many causes leading to renal
      tubular dysfunction, beta-thalassemia minor has not been reported among them in
      reviewing the literature. In a 20-year-old male patient referred to us because of
      glucosuria detected with dipstick, there was also anemia (hemoglobin, 11.5 g/dl;
      mean cell volume, 60 fl; and mean cell hemoglobin concentration, 19.5 pg). The 24
      hour urinary glucose excretion rate was 5 g and, additionally, he had tubular
      proteinuria (albumin/beta(2)-microglobulin ratio in urine was 17.32). Based upon
      the detailed evaluation for both asymptomatic urinary abnormality and anemia, he
      was diagnosed as having renal tubular dysfunction and beta-thalassemia minor
      (hemoglobin A(1)was 91%, and hemoglobin A(2)was 9%). In conclusion, further
      reports are needed to reveal whether there is an association between these two
      distinct disorders.

PMID- 12187109
TI  - Serum cystatin C is a more sensitive marker of glomerular function than serum
      creatinine.
AB  - We determined the relationship between the levels of serum cystatin C or
      creatinine (s-Cr) and the grade of creatinine clearance (CCr) in patients with
      various glomerular diseases. Serum samples from 96 patients with glomerular
      diseases were obtained from our hospital. The levels of serum cystatin C were
      measured using the Dade Behring Cystatin C assay with the automated Dade Behring
      Nephelometer II (BNII). CCr levels were classified into six groups according to
      the Guidelines of the Japanese Society of Nephrology as follows: grade 1 (normal
      renal function); grade 2 (slight decrease of renal function); grade 3 (moderate
      decrease of renal function); grade 4 (severe decrease of renal function); grade 5
      (renal failure), and grade 6 (uremia). The mean levels of serum cystatin C in
      grade 3 patients were significantly higher than those in grade 1. The mean levels
      of serum cystatin C in grades 4, 5 and 6 patients were also significantly higher
      than those in grade 1. However, the mean levels of serum Cr in grade 3 patients
      were not significantly higher than those in grade 1. The levels of s-Cr in grades
      4, 5 or 6 patients were significantly higher than those in grade 1. In this
      study, an increase of serum cystatin C levels occurred earlier than that of s-Cr
      in various glomerular diseases. It appears that the levels of serum cystatin C
      may provide early prognostic marker of patients with various glomerular diseases
      rather than the levels of s-Cr.

PMID- 12187110
TI  - Renal cell carcinoma complicated by emphysematous pyelonephritis in a non
      diabetic patient with renal failure.
AB  - A 72-year-old non-diabetic uremic woman underwent right nephrectomy for
      urolithiasis at the age of 50. Because pyuria, fever, chilliness and left flank
      pain developed during preparing for arteriovenous fistula, she was admitted to
      National Cheng Kung University Hospital. Renal cell carcinoma (RCC) complicated
      with emphysematous pyelonephritis (EPN) was diagnosed and immediately treated
      with antibiotics and CT-guided percutaneous catheter drainage. Cultures of pus
      and blood yielded Escherichia coli. She received left radical nephrectomy later
      for the control of persistent sepsis and removal of left renal tumor. The
      pathology of the tumor was composed of a glandular arrangement of granular cells
      with the occasional atypism, and renal parenchyma had been totally replaced by
      RCC. The non-tumor part of the kidney showed chronic pyelonephritis. Five months
      later, multiple metastases developed. We reported this first uremic case with EPN
      and RCC, but without diabetes mellitus and urinary tract obstruction. The gas
      formation may be due to large RCC, which caused impaired tissue perfusion and E.
      coli infection.

PMID- 12187111
TI  - Importance of serum ferritin levels in patients with renal failure.
AB  - Study results on acute phase reactants of renal failure patients are
      controversial. In this study, we enrolled 39 patients and divided them into 2
      groups: acute renal failure (ARF), and chronic renal failure (CRF) patients. As
      opposed to CRF patients, the patients with ARF had higher serum ferritin levels
      that were independent of anemia parameters and other acute phase reactants.

PMID- 12187112
TI  - Pure red cell aplasia preceding malignant lymphoma in a renal transplant patient.
AB  - Malignant disorders are one of the major causes of morbidity and mortality in
      transplant patients. We present herein a renal transplant recipient with
      malignant lymphoma which preceded by pure red cell aplasia (PRCA). Acquired PRCA
      is a rare hematologic disorder in renal transplant recipients. It has been
      associated with a variety of disorders of immunologic dysfunction and neoplasms,
      exposure to drugs and toxins, infectious diseases, pregnancy and severe
      nutritional deficiency. This is the first case with PRCA preceding the malign
      lymphoma in a renal transplant patient. Treatment of lymphoma and lymphoma
      related humoral and cellular changes or other undefined effects that may be
      related to therapy may be responsible of the resolving of PRCA in this patient.
      In this regard, renal transplant patients with acquired PRCA, must be closely
      followed for an underlying neoplastic disorder.

PMID- 12187113
TI  - Methylenetetrahydrofolate reductase gene C677T polymorphism, plasma homocysteine
      and folate in end-stage renal disease dialysis and non-dialysis patients.
AB  - BACKGROUND: It has been recently suggested that the presence of the
      methylenetetrahydrofolate reductase gene 677TT genotype is associated with
      younger age at initiation of dialysis, thus raising a hypothesis that younger
      renal patients carrying the TT genotype are at higher risk to develop end-stage
      renal disease. The aim of this study was to test the association between the
      C677T polymorphism and the presence of end-stage renal disease using a family
      based study design. MATERIAL AND METHOD: C677T polymorphism was genotyped in a
      group of 247 family trios (offspring affected with end-stage renal disease,
      dialysed or conservatively treated, and both parents).
      Transmission/disequilibrium test (TDT) was used to evaluate allele transmission
      from heterozygous parents to affected offspring. RESULTS: The TDT analysis
      revealed no significant deviation in the transmission of the MTHFR C677T alleles
      to CRF patients (51 vs. 49% for the C allele and T allele transmission,
      respectively). We observed a significant relationship between MTHFR genotypes and
      total plasma homocysteine (tHcy), as well as folate concentration. Also, plasma
      tHcy and folate were negatively correlated. CONCLUSION: Our results did not show
      any association between the MTHFR reductase C677T polymorphism and the increased
      risk of the development of end-stage renal disease. Whether this polymorphism
      contributes to the faster rate of decline of renal function in renal patients,
      must be evaluated further.

PMID- 12187114
TI  - Recovery from hemodialysis therapy in a patient with renal cholesterol crystal
      embolism.
AB  - The prognosis of renal cholesterol crystal embolism (CCE) is poor, and many
      patients progressively develop to the end-stage of chronic renal failure. We
      herein experienced a 66-year-old male patient who recovered from hemodialysis
      (HD) shortly after an amputation of inflammatory toes. The patient complained of
      painful digital cyanosis at bilateral toes and livedo reticularis at right lower
      leg 4 weeks following aortic angiography. Laboratory examinations revealed
      eosinophilia and overt proteinuria (3.0 g/day). His serum creatinine level
      increased from 2.18 to 8.57 mg/dl over 6 weeks, and HD treatment was started.
      Treatment with simvastatin (5 mg/day) did not reverse renal failure and
      hypereosinophilia, but the amputation of right gangrene toes promptly increased
      urine output and eosinophilia completely disappeared concomitantly with a decline
      of C-reactive protein from 9.7 to 0.7 mg/dl. Serum creatinine level was also
      reduced to 3.46 mg/dl, and he eventually stopped HD totally after 32 sessions.
      This case suggested that the surgical amputation promptly recovered renal
      function. Reversal of inflammation may be more effective than lipid-lowering
      therapy for renal failure in our patient.

PMID- 12187115
TI  - An unusual presentation for nephrotic syndrome. Bilateral perirenal subcapsular
      fluid collection.
AB  - We present a 30-year-old man with nephrotic syndrome presenting with bilateral
      perirenal massive collection compatible with transudation. After drainage of
      collections kidney biopsy was performed and the histologic diagnosis was focal
      and segmental glomerulosclerosis. The patient was treated with cyclophosphamide,
      prednisone, furosemide and enalapril. After remission of nephrotic syndrome renal
      ultrasound showed complete resolution of perirenal collections. In conclusion,
      the case shows that perirenal subcapsular transudation is a rare complication of
      nephrotic syndrome and massive collections can be treated successfully by
      percutaneous drainage.

PMID- 12187116
TI  - Donor-specific transfusion and renal allograft outcome.

PMID- 12187117
TI  - Hypothyroidism as a cause of resistance to erythropoietin.

PMID- 12187118
TI  - Treatment with ticlopidine is associated with reduction of cyclosporin a blood
      levels.

PMID- 12187119
TI  - Penile arteries and erection.
AB  - Alterations in the flow of blood to and from the penis are thought to be the most
      frequent causes of male erectile dysfunction and, therefore, the present review
      focuses on the penile vasculature. In the flaccid state, tonic noradrenaline
      release from the sympathetic nerves contracts penile arterial and corporal smooth
      muscle through activation of postjunctional alpha(1)-adrenoceptors, both by
      increasing intracellular calcium and by enhancing the sensitivity of the
      contractile apparatus for calcium. In addition, noradrenaline inhibits
      vasodilatatory neurotransmitter release by prejunctional alpha(2)-adrenoceptors.
      The exact role of the sympathetic neurotransmitters, neuropeptide Y and adenosine
      5'-triphosphate, in erection is largely unknown. Penile vasodilatation during
      erection is mediated by nitric oxide (NO) through activation of guanylyl cyclase
      in the smooth muscle layer, followed by increases in cyclic guanosine
      monophosphate lowering of intracellular calcium and desensitisation of the
      contractile apparatus for calcium. Acetylcholine, vasoactive intestinal peptide
      as well as peptides in sensory nerves probably also play a role in penile
      vasodilation. Increased flow through the penile arteries stimulates the
      endothelium leading to release of NO, prostanoids and a non-NO non-prostanoid
      factor, and as such enhances the vasodilatation, while the role of endothelium
      derived contractile factors in penile vasoconstriction is not clear. Erectile
      dysfunction shares arterial risk factors with ischaemic heart disease, and
      diabetes, age, and hypercholesterolaemia are associated with impairment of both
      neurogenic and endothelium-dependent vasodilator mechanisms in corpus cavernosum.
      Only few studies have investigated the impact of these risk factors on the penile
      vasculature, although recent evidence suggests that arterial insufficiency
      precedes changes in corpus cavernosum leading to erectile dysfunction.

PMID- 12187120
TI  - Differential expression of genes from nitrate-tolerant rat aorta.
AB  - Organic nitrates act as vasodilators and have long been used for treatment of
      cardiovascular diseases. However, the therapeutic effect of nitrates is limited
      by induction of nitrate tolerance which is associated with endothelial
      dysfunction and enhanced vasoconstriction. Multiple mechanisms cause nitrate
      tolerance including alterations in gene expression. To identify genes whose
      expression is altered due to chronic treatment with nitroglycerin (NTG), nitrate
      tolerant rats were made by infusion of NTG for 3 days (10 microg/kg/min) using an
      osmotic minipump. We constructed a PCR-selected cDNA subtracted library from NTG
      treated and vehicle-treated rat aortas. Screening of approximately 500 clones in
      the subtracted library showed that four genes were regulated by NTG treatment.
      Specifically, mRNA levels of beta-globin, tropoelastin, gelsolin and a small G
      protein were confirmed to be upregulated consistently by NTG treatment. These
      identified genes may play important roles in the development of nitrate tolerance
      and represent promising candidates to understand the mechanisms of nitrate
      tolerance and endothelial dysfunction in the vasculature.

PMID- 12187121
TI  - Vascular function in women with previous gestational diabetes mellitus.
AB  - It is hypothesised that vascular dysfunction, which characterises type 2
      diabetes, may predate development of hyperglycaemia. 17 women with previous
      gestational diabetes mellitus, and thus at risk of developing type 2 diabetes,
      were matched with normal controls for body mass index, menstrual phase, smoking,
      age, blood pressure, and lipid profiles. All had normal glucose tolerance. Tests
      of microvascular and macrovascular function, including endothelium-dependent and 
      independent vasodilatation, were performed. Laser Doppler fluximetry of maximum
      skin microvascular hyperaemia in response to local heating of the dorsum of the
      foot to 42 degrees C for 30 min was impaired in subjects compared to controls
      [subjects = 1.15 (0.73-1.73) V median (range) versus controls = 1.50 (0.95-2.29)
      V, p = 0.008]. There were no differences in laser Doppler perfusion imaging of
      responses to forearm skin iontophoresis of acetylcholine [subjects = 1.59 (0.32
      2.55) V median (range) versus controls = 1.79 (0.72-2.06) V; p = 0.81] and sodium
      nitroprusside [subjects = 1.39 (0.8-3.14) V versus controls = 1.41 (0.34-2.19) V;
      p = 0.68], ultrasound estimation of brachial artery flow-mediated dilatation
      [subjects = 1.65 (-0.5-9.07)% versus controls = 2.77 (0.63-6.6)%; p = 0.42] and
      glyceryl trinitrate-induced dilatation [subjects = 15.20 (6.64-20.91)% versus
      controls = 15.92 (3.94-22.09)%; p = 0.48]. Microvascular maximum hyperaemia was
      impaired in the index group, suggesting the presence of a defect in vascular
      function. This defect was not explained by those aspects of endothelial function
      measured by the other techniques.

PMID- 12187122
TI  - Pancreatic protease inhibition during shock attenuates cell activation and
      peripheral inflammation.
AB  - Intestinal ischemia contributes to shock-induced multiple organ failure. Our
      recent evidence suggests that pancreatic proteases may be involved in the
      formation of inflammatory activators within an ischemic intestine. These
      inflammatory mediators are released early into the circulation and may contribute
      to the severe systemic inflammatory response syndrome (SIRS) during shock. We
      examined the impact of intra-intestinal pancreatic protease inhibition on acute
      intestinal ischemia-induced hypotension, the formation of activating factors for
      cardiovascular cells, as well as cremaster muscle cell death and intestinal
      injury by intravital microscopy. Male Wistar rats were divided into four groups:
      (1) a sham group; and experimental groups with 100 min of superior mesenteric
      artery occlusion (2) without (SMAO group), and (3) with intestinal lavage using
      Krebs-Henseleit solution (LAV group), or (4) lavage using the protease inhibitor
      gabexate mesilate in Krebs-Henseleit solution (FOY group, 0.37 mM). Intestinal
      ischemia and reperfusion-induced hypotension upon reperfusion was accompanied by
      a significant increase in the level of neutrophil-activating factors in the
      intestine and plasma. During reperfusion, a significant increase in leukocyte
      endothelium interactions in postcapillary venules and parenchymal cell death were
      observed in the cremaster muscle in LAV and SMAO animals suggesting peripheral
      neutrophil cell activation. Intra-intestinal pancreatic protease inhibition
      resulted in a stable blood pressure throughout the experiment. Cell activation,
      leukocyte-endothelial interactions and cell death in the cremaster muscle were
      almost completely abolished in the FOY group. In addition, ischemia-induced
      intestinal mucosal injury was attenuated with intestinal pancreatic protease
      inhibition. These results indicate that intestinal pancreatic protease inhibition
      significantly attenuates intestinal ischemia-induced shock by reducing SIRS and
      gut injury.

PMID- 12187123
TI  - Platelet kinetics in the pulmonary microcirculation in vivo assessed by
      intravital microscopy.
AB  - Growing evidence supports the substantial pathophysiological impact of platelets
      on the development of acute lung injury. Methods for studying these cellular
      mechanisms in vivo are not present yet. The aim of this study was to develop a
      model enabling the quantitative analysis of platelet kinetics and platelet
      endothelium interaction within consecutive segments of the pulmonary
      microcirculation in vivo. New Zealand White rabbits were anesthetized and
      ventilated. Autologous platelets were separated from blood and labeled ex vivo
      with rhodamine 6G. After implantation of a thoracic window, microhemodynamics and
      kinetics of platelets were investigated by intravital microscopy. Velocities of
      red blood cells (RBCs) and platelets were measured in arterioles, capillaries and
      venules, and the number of platelets adhering to the microvascular endothelium
      was counted. Kinetics of unstimulated platelets was compared with kinetics of
      thrombin-activated platelets. Velocity of unstimulated platelets was comparable
      to RBC velocity in all vessel segments. Unstimulated platelets passed the
      pulmonary microcirculation without substantial platelet-endothelial interaction.
      In contrast, velocity of activated platelets was decreased in all vascular
      segments indicating platelet margination and temporal platelet-endothelium
      interaction. Thrombin-activated platelets adhered to arteriolar endothelium; in
      capillaries and venules adherence of platelets was increased 8-fold and 13-fold,
      respectively. In conclusion, using intravital microscopy platelet kinetics were
      directly analyzed in the pulmonary microcirculation in vivo for the first time.
      In contrast to leukocytes, no substantial platelet-endothelium interaction occurs
      in the pulmonary microcirculation without any further stimulus. In response to
      platelet activation, molecular mechanisms enable adhesion of platelets in
      arterioles and venules as well as retention of platelets within capillaries.

PMID- 12187124
TI  - Characterization of differential gene expression in quiescent and invasive human
      arterial smooth muscle cells.
AB  - Proliferation, migration and invasion of smooth muscle cells (SMCs) are essential
      pathogenic processes in the development of a broad spectrum of cardiovascular
      disorders, like arteriosclerosis, restenosis after percutaneous transluminal
      angioplasty and stent implantation as well as transplant vessel disease. As an in
      vitro model mimicking these processes, the Boyden chamber was employed to
      characterize the diverging migratory and invasive potentials of proliferating and
      nonproliferating human arterial SMCs (haSMCs). Using this model, differential
      gene expression of both phenotypes was analyzed by a cDNA array system (Clontech
      human cardiovascular array). With these arrays, 558 cardiovascular-associated
      genes could be compared. Further, gene expression was exactly quantified by real
      time RT-PCR. Protein expression was analyzed by ELISA and Western blotting. In
      total, 47 genes were differentially expressed more than 1.5 times. Most of the
      differentially regulated genes in this study were associated with the
      extracellular matrix (ECM) and cell motility. In detail, the respective groups
      were matrix-organizing proteins, ECM proteins, cell adhesion proteins,
      extracellular communication and cytoskeleton motility proteins. Genes known to be
      differentially regulated during haSMC migration and invasion, like TIMP 2, TIMP
      3, and MMP 3, were confirmed by the array data. Reduced expression of several
      cytoskeletal proteins, like vimentin, fibronectin, cytokeratins and beta1
      integrin, was shown in the invasive phenotype. Further, angio-associated protein,
      alpha E-catenin and atrial brain natriuretic peptide receptor were downregulated
      whereas TFPI 2 was strongly upregulated in invasive haSMCs. In conclusion,
      several relevant potential candidate genes for the quiescent and the invasive SMC
      phenotype were identified and genes already known to be differentially regulated
      by previous analysis were confirmed.

PMID- 12187125
TI  - p38 mitogen-activated protein kinase activation is required for thromboxane-
      induced contraction in perfused and pressurized rat mesenteric resistance
      arteries.
AB  - Thromboxane A(2) (TxA2) is a potent proaggregating, vasoconstrictor agent
      produced in many physiological and pathological situations. Although mitogen
      activated protein (MAP) kinases [MAPK (ERK1/2 and p38)] have been shown to be
      activated after endoperoxide/thromboxane receptor (TP) stimulation, no study has
      investigated their potential role in resistance arteries, especially in
      physiological conditions of pressure and flow in which the arteries can contract.
      Thus, responses to TP stimulation by the stable agonist U46619 were studied in
      isolated rat mesenteric resistance arteries (inner diameter 262 +/- 5 microm)
      mounted in an arteriograph. Changes in diameter were recorded under physiological
      levels of flow (90 microl/min) and pressure (50 mm Hg). TP stimulation induced a
      concentration-dependent contraction (EC(50) value of 1.94 +/- 0.22 x 10(-7) M),
      without desensitization. U46619-induced contraction was inhibited by calcium
      entry blockade (nifedipine) and protein kinase C inhibition (GF109203X), but it
      was not affected by tyrosine kinase inhibition (tyrphostin A25). MAPKK (MEK)
      inhibition (PD98059) did not alter U46619-dependent contraction, although ERK1/2
      MAPK were activated. By contrast, p38 MAPK inhibition (SB203580) dose-dependently
      inhibited the contraction, and Western blot analysis showed activation of p38
      MAPK in arteries contracted with U46619. Activation of p38 MAPK by U46619 was
      inhibited by nifedipine and in the absence of extracellular calcium. This study
      brings new insights in the transduction pathway involved in the contractile
      response of resistance arteries to TxA2/endoperoxide receptor stimulation. This
      contraction requires p38 MAPK activation, but did not involve ERK1/2 MAPK
      activation although both were activated.

PMID- 12187126
TI  - External collar inhibits balloon-induced intimal hyperplasia in rabbits.
AB  - Intimal hyperplasia is a common complication following vascular interventions. To
      understand the underlying pathophysiology, the focus has mainly been on the
      intima and media. The adventitia has been less investigated, although adventitial
      hyperplasia is seen together with intimal hyperplasia. If the adventitial
      response is an important part of the process, the adventitia might be a target to
      inhibit intimal hyperplasia. In the present study we investigated whether an
      external collar attenuating the adventitial thickness could inhibit a balloon
      induced intimal hyperplasia. The common carotid artery was injured in rabbits (n
      = 6) with a 3-french balloon catheter. The mid portion of the injured artery was
      encircled with a silicone collar (diameter = 2.0 mm). After 14 days the balloon
      induced neointima was reduced by 54 +/- 6.3% underneath the collar. The
      adventitial and medial thickenings were also attenuated (36 +/- 8.7 and 44 +/-
      4.3%, respectively). This study demonstrates that intimal hyperplasia following
      balloon injury can be inhibited with an external collar. This supports the idea
      of the adventitia as a potential target to inhibit intimal hyperplasia.

PMID- 12187127
TI  - OPS imaging of human microcirculation: a short technical report.
AB  - Despite the pivotal role of microcirculation in numerous diseases, techniques for
      the direct assessment of human microcirculation are limited. A new approach based
      on orthogonal polarization spectral (OPS) imaging (Cytoscan microscope) allows
      noninvasive observation of human microcirculation in all accessible tissue
      surfaces. Limitations remain: application of pressure with the instrument affects
      blood flow, lateral movement of tissue precludes continuous investigation of a
      given microvascular region, and blood flow velocities above 1 mm/s cannot be
      measured. We addressed these problems by (a) constructing an attachment to the
      probe, preventing direct contact of the instrument with the observed tissue area
      and allowing fixation of the tissue, and (b) implementing a double-flash spatial
      correlation technique extending the measuring range for blood flow velocities up
      to approximately 40 mm/s. The modified approach was tested in vitro and in vivo.
      Velocity readings correlated well with velocities of an external standard (r(2) =
      0.99, range 1.9-33.8 mm/s). Pulsatile flow patterns synchronous with heart rate
      with maximal velocities of about 10 mm/s could be detected in arterioles of the
      human sublingual mucosa. The modified instrument may prove useful to investigate
      the microcirculation in the context of research, diagnosis and therapy control.

PMID- 12187128
TI  - Carbon dioxide monitoring in emergency medicine training programs.
AB  - OBJECTIVES: Although the measurement of carbon dioxide (CO2) in breath is the
      standard of care for verification of endotracheal tube placement in all
      anesthesia practice and in the prehospital setting, there is currently no uniform
      consensus on the status of CO2 monitoring in emergency medicine. We conducted
      this survey to delineate practice patterns of CO2 monitoring in academic
      emergency medicine training programs and to describe the preference for type of
      CO2 monitoring device. METHODS: We surveyed the availability, presence, and types
      of CO2 monitoring in all general emergency medicine (GEM) residency programs and
      all pediatric emergency medicine (PEM) fellowship programs. A two-question survey
      was used, and data were collected from March 1998 to June 1998. The clinicians
      surveyed were asked whether their emergency department (ED) used CO2 monitoring
      for detection of endotracheal tube placement and, if so, what type of CO2
      monitoring devices was used. Types of CO2 monitoring devices were categorized as
      colorimetric, capnometric, capnographic, or combinations of these. RESULTS: Of
      the 168 programs surveyed, all GEM and PEM programs responded, and the survey
      results showed that 136 of 168 (81%) used some form of CO2 monitoring, and 32 of
      168 (19%) did not use CO2 monitoring. The majority of programs (115/168, 68%)
      used a single device. Colorimetric devices were used most frequently (76/168,
      45%), and capnometry was used the least (9/168, 5%). PEM programs had a
      significant preference for quantitative CO2 monitoring, whereas GEM programs had
      a significant preference for qualitative CO2 monitoring. CONCLUSIONS: Although
      the majority of academic emergency medicine training programs used CO2
      monitoring, 19% did not. Colorimetric devices were the most frequently used CO2
      monitoring technology.

PMID- 12187129
TI  - Constipation: diagnosis and management in the pediatric emergency department.

PMID- 12187130
TI  - Ceftriaxone use in the emergency department: are we doing it right?
AB  - OBJECTIVE: To evaluate the patterns of ceftriaxone use in an urban pediatric
      emergency department (PED) and to determine if overuse exists based on published
      guidelines for management of febrile infants. METHODS: We conducted a
      retrospective study of 229 young febrile patients who received ceftriaxone
      between January 1 and March 31, 1995, in a large urban PED in a teaching hospital
      in Atlanta. Patients younger than 3 months, patients with chronic illnesses (eg,
      sickle cell anemia, HIV), and those who received ceftriaxone for sexually
      transmitted diseases were excluded. RESULTS: During the study period, ceftriaxone
      was administered 289 times to 229 patients (53% male) aged 3 months to 18 years.
      Sixty patients (26%) received ceftriaxone two or more times for the same illness.
      Data were stratified based on age, source of fever, temperature, leukocyte count,
      diagnosis of pneumonia, and visit order (initial or follow-up). At the time of
      their initial visit, 180 of 229 patients had an identifiable focus of infection
      (76 had pneumonia), but no source could be identified in the remaining 49. Based
      on temperature, leukocyte count, and the presence or absence of a focus,
      ceftriaxone use, as compared with practice guidelines, was justified in 40 of 229
      (17.5%) patients, questionable in 43 of 229 (18.8%), and not justified in 146 of
      229 (63.7%). For the 60 patients who received ceftriaxone more than once, its use
      was justified in only 13%. Results of blood cultures were positive in 3 of 229
      (1.3%) patients. Ceftriaxone was justified according to published guidelines in
      two of these three patients, whereas one patient with pneumonia and pneumococcal
      bacteremia could have been treated with oral antibiotics. Overall, for the entire
      study population (289 encounters at initial and subsequent visit combined),
      ceftriaxone use was justified in 48 patients (16.6%), questionable in 49 patients
      (17%), and not justified in 192 patients (66.4%). CONCLUSIONS: Based on published
      guidelines, ceftriaxone use in the PED was not justified in the majority of
      cases.

PMID- 12187131
TI  - Pigtail catheters versus large-bore chest tubes for pneumothoraces in children
      treated in the emergency department.
AB  - OBJECTIVE: We sought to compare the efficacy (pneumothorax resolution and
      hospitalization days), pain (narcotic usage), and safety (need for repositioning
      or replacement) associated with placement of large-bore chest tubes versus
      pigtail catheters in children with pneumothoraces. METHODS: We conducted a
      retrospective chart review of all patients with pneumothoraces seen in the
      emergency department (ED) over a 6.5-year period who received treatment by a
      pediatric emergency physician with either a large-bore chest tube or a pigtail
      catheter. We excluded patients who had catheters placed by other specialists and
      patients who were endotracheally intubated. We collected the following data:
      complications, hospital days to discharge, and narcotic pain medications taken.
      RESULTS: Eleven pigtail catheters and 16 large-bore chest tubes were placed. All
      pneumothoraces were effectively evacuated. Three of the 11 pigtail catheters
      required repositioning, and one was replaced. Two of the 16 large-bore chest
      tubes were repositioned, and one was replaced; additionally, a pigtail catheter
      was added to one patient with a large-bore chest tube to facilitate evacuation of
      the air. Average hospital stay was similar between groups (6.2 d for pigtail
      catheters vs 6.8 d for large-bore chest tubes, = 0.74). Children with pigtail
      catheters required less narcotic pain medications than those who had large-bore
      chest tubes, but the differences were not significant. CONCLUSION: Pigtail
      catheters offer a safe and effective alternative to large-bore chest tubes for
      patients receiving treatment for pneumothoraces in the ED.

PMID- 12187132
TI  - Psychiatric emergencies in children.
AB  - OBJECTIVE: To examine the demographic and clinical characteristics of children
      using the pediatric emergency department (ED) in a medical center in Baltimore,
      Maryland. The rate of admission and length of stay for children who were
      evaluated in the ED were also examined. SETTING: A large, urban medical center
      with approximately 15,500 visits per year. RESULTS: During a 13-month period,
      more than 600 visits to the ED were made for mental health concerns for children
      aged 2 to 18 years, with psychiatric visits constituting more than 5% of total
      visits to the ED. Psychiatric visits averaged more than 5 hours' duration in the
      ED and involved significant effort by medical staff, with approximately one half
      of visitors undergoing psychiatric admission. Interviews conducted with the ED
      staff revealed that addressing psychiatric problems in children is a considerable
      burden and that there is a general lack of resources within the ED and the
      surrounding community to respond to the needs of children with psychiatric
      emergencies. CONCLUSION: The challenge in most communities is to build a true
      system of care that involves proactive and more preventive care in natural
      settings, such as schools, and coordination and improvement of care for youth
      with more serious problems.

PMID- 12187134
TI  - Pericardial effusions in a pediatric emergency department.

PMID- 12187133
TI  - The importance of cultural and linguistic issues in the emergency care of
      children.
AB  - BACKGROUND: Rapid growth in the diversity of the US population makes it
      increasingly likely that emergency clinicians will encounter greater numbers of
      patients from different cultures, but little is known about the importance of
      culture and language in the emergency care of children. OBJECTIVE: To conduct a
      critical review and synthesis of published studies on culture and language in the
      emergency care of children. METHODS: PubMed was used to perform a literature
      search (using 17 search terms) of all articles on culture, language, and the
      emergency care of children published in English or Spanish from 1966 to 1999.
      RESULTS: More than 2000 citations initially were identified; consensus review
      yielded 400 papers that were photocopied. A final database of 117 articles
      revealed the following: certain normative cultural values, such as the Navajo
      hozhooji (the importance of thinking and speaking positively), can have profound
      effects on informed consent and discussions of medical risk. For limited English
      proficient children and their families, studies document that medical
      interpreters frequently are not used, there is a lack of trained interpreters,
      there are more access barriers, and those who need but do not get interpreters
      have poor understanding of their diagnosis and treatment. Numerous folk
      illnesses, such as among Latinos, can affect care, because symptoms often overlap
      with important biomedical conditions, the first clinical contact may be with folk
      healers, and certain folk remedies are harmful or even fatal. Certain parent
      beliefs and practices can result in serious morbidity and fatalities (from lead
      poisoning, liver failure, and other causes), costly or unnecessary medical
      evaluations (eg, Fenugreek teas), and clinical findings easily confused with
      child abuse (eg, coining). Biased provider attitudes and practices can have
      profound clinical consequences, including ethnic disparities in prescriptions,
      analgesia, test ordering, sexual history taking, asthma care quality, and
      diagnostic evaluations. CONCLUSIONS: Failure to appreciate the importance of
      culture and language in pediatric emergencies can result in multiple adverse
      consequences, including difficulties with informed consent, miscommunication,
      inadequate understanding of diagnoses and treatment by families, dissatisfaction
      with care, preventable morbidity and mortality, unnecessary child abuse
      evaluations, lower quality of care, clinician bias, and ethnic disparities in
      prescriptions, analgesia, test ordering, and diagnostic evaluations.

PMID- 12187135
TI  - Rare cause of bilious emesis in a 7 month old.

PMID- 12187136
TI  - Near-fatal strangulation injury: a unique case caused by a turnstile.

PMID- 12187137
TI  - Pediatric clonidine poisoning as a result of pharmacy compounding error.

PMID- 12187138
TI  - Re-expansion pulmonary edema in an adolescent girl.

PMID- 12187139
TI  - Cecal volvulus in childhood.

PMID- 12187140
TI  - Bronchiolitis cases.

PMID- 12187141
TI  - Pediatric emergency medicine: legal briefs.

PMID- 12187143
TI  - Hip and leg pain causing total loss of mobility.

PMID- 12187142
TI  - A 4-month-old infant with fever and cough.

PMID- 12187144
TI  - Lower gastrointestinal bleeding in children.
AB  - Lower gastrointestinal bleeding is a common problem in the practice of general
      pediatrics. The differential diagnosis can be extensive and varies according to
      the age of the child. A specific diagnosis can usually be made with a thorough
      history, physical examination, simple laboratory investigations, and appropriate
      diagnostic studies. Treatment should be directed at the underlying cause. In most
      children, bleeding ceases spontaneously, and only supportive therapy is
      necessary. If there is evidence of hypovolemia, the patient must be
      hemodynamically stabilized, active bleeding stopped, and recurrent bleeding
      prevented.

PMID- 12187145
TI  - Unintentional victims: development of a protocol for the care of children exposed
      to chemicals at methamphetamine laboratories.

PMID- 12187146
TI  - Comparison of ventriculoperitoneal shunt tap and lumbar puncture in a child with
      meningitis.

PMID- 12187147
TI  - Traumatic arterial priapism: case report and discussion of a rare urologic
      injury.

PMID- 12187148
TI  - Multiorgan failure due to coarctation of the aorta: management and outcome of
      five neonates.
AB  - Coarctation of the aorta can manifest in a number of ways. Differential diagnosis
      is particularly difficult during the neonatal period, especially in newborns
      presenting with a sepsis-like or metabolic disease-like condition. We describe
      five newborns who presented with metabolic acidosis, renal insufficiency, or
      ischemic hepatitis and stress the importance of early diagnosis to prevent
      adverse outcome.

PMID- 12187149
TI  - Cardiac irritability and myocardial infarction in a 13-year-old girl following
      recreational amphetamine overdose.

PMID- 12187150
TI  - A guest editorial: antibiotic selection in obstetrics and gynecology.

PMID- 12187151
TI  - Assisted reproductive technologies: toward improving implantation rates and
      reducing high-order multiple gestations.
AB  - Despite striking progress in reproductive medicine over the past quarter century,
      the number of high-order multiple gestations are unacceptably high, largely as a
      result of the drive to maintain pregnancy rates in a competitive range.
      Morphologic criteria are currently used to define the reproductive competence of
      individual embryos but are imperfect predictors of implantation potential.
      Current and potential strategies to improve the selection of embryos are
      described. By the use of several of these approaches, it is hoped that the
      overall number of embryos that are transferred will be reduced, thereby also
      reducing the multiple gestation rate.

PMID- 12187152
TI  - Consanguineous marriage and its relevance to obstetric practice.
AB  - At the beginning of the twenty-first century, consanguineous marriage is
      practiced widely in many parts of the world. More than 2 billion people, of
      various religious and ethnic backgrounds, live in countries where a large
      proportion of marriages are contracted between blood relatives. The practice is
      seen as promoting family stability and having significant social and economic
      advantages. Consanguineous marriage is important genetically-the children of
      consanguineous unions are more often homozygous for particular alleles than are
      the offspring of unrelated parents, and therefore, autosomal recessive disorders,
      which may be lethal or debilitating, are more common in such children. Health
      care providers working with communities where consanguineous marriage is common,
      in particular obstetricians, family physicians, and pediatricians, need to be
      aware of the possible impact of such marriages on pregnancy outcomes, so the best
      possible genetic and antenatal care can be provided, sympathetically and
      nonjudgmentally, and the best possible results obtained.

PMID- 12187153
TI  - Ectopic pregnancy within a cesarean scar: a review.
AB  - Implantation of a pregnancy within the scar of a previous cesarean delivery is
      the rarest of ectopic pregnancy locations. Only 19 cases have been reported in
      the English medical literature since 1966. If diagnosed early, treatment options
      are capable of preserving the uterus and subsequent fertility. However, a delay
      in either diagnosis or treatment can lead to uterine rupture, hysterectomy, and
      significant maternal morbidity. Although expectant and medical managements have
      been reported, termination of a cesarean scar pregnancy by laparotomy and
      hysterotomy, with repair of the accompanying uterine scar dehiscence, may be the
      best treatment option.

PMID- 12187163
TI  - Overview of the SEER-Medicare data: content, research applications, and
      generalizability to the United States elderly population.
AB  - BACKGROUND: The Surveillance, Epidemiology and End Results (SEER)-Medicare-linked
      database combines clinical information from population-based cancer registries
      with claims information from the Medicare program. The use of this database to
      study cancer screening, treatment, outcomes, and costs has grown in recent years.
      RESEARCH DESIGN: This paper provides an overview of the SEER-Medicare files for
      investigators interested in using these data for epidemiologic and health
      services research. The overview includes a description of the linkage of SEER and
      Medicare data and the files included as part of SEER-Medicare. The paper also
      describes the types of research projects that have been undertaken using the SEER
      Medicare data. The overview concludes with a comparison of selected
      characteristics of elderly persons residing in the SEER areas to the US total
      aged. RESULTS: The paper identifies a number of potential uses of the SEER
      Medicare data. The comparison of the elderly population in SEER areas to the US
      total shows that in the SEER areas there are a lower percentage of white persons
      and individuals living in poverty, and a higher percentage of urban-dwellers than
      the US total. Elderly persons in the SEER regions also have higher rates of HMO
      enrollment and lower rates of cancer mortality. CONCLUSIONS: The SEER-Medicare
      data are a unique resource that can be used for a variety of health services
      research projects. Although there are some differences between the elderly
      residing in the SEER areas and the US total, the SEER-Medicare data offer a large
      population-based cohort that can be used to longitudinally track care for persons
      over the course of cancer diagnosis, treatment, and follow-up.

PMID- 12187164
TI  - Patient demographic and socioeconomic characteristics in the SEER-Medicare
      database applications and limitations.
AB  - Users of the linked SEER-Medicare database commonly perform analyses that focus
      on the complex interactions among patient characteristics, cancer treatments, and
      outcomes. The authors review the source and scope of the patient-specific data
      elements, with a focus on three domains--demographic characteristics,
      socioeconomic characteristics, and survival status. They offer some concrete
      recommendations regarding the use of these data elements. In particular, they
      describe analyses that provide an estimate of the accuracy of the sex and age
      variables, and raise some cautionary notes about race and ethnicity variables.
      The authors describe the available measures of socioeconomic status, and
      recommend, with some caveats, the use of median income measures as a proxy for
      socioeconomic status. Finally, they describe the available data on date of death,
      and explain why confidence in these measures is justified.

PMID- 12187165
TI  - Assessing comorbidity using claims data: an overview.
AB  - Comorbidity, additional disease beyond the condition under study that increases a
      patient's total burden of illness, is one dimension of health status. For
      investigators working with observational data obtained from administrative
      databases, comorbidity assessment may be a useful and important means of
      accounting for differences in patients' underlying health status. There are
      multiple ways of measuring comorbidity. This paper provides an overview of
      current approaches to and issues in assessing comorbidity using claims data, with
      a particular focus on established indices and the SEER-Medicare database. In
      addition, efforts to improve measurement of comorbidity using claims data are
      described, including augmentation of claims data with medical record, patient
      self-report, or health services utilization data; incorporation of claims data
      from sources other than inpatient claims; and exploration of alternative
      conditions, indices, or ways of grouping conditions. Finally, caveats about
      claims data and areas for future research in claims-based comorbidity assessment
      are discussed. Although the use of claims databases such as SEER-Medicare for
      health services and outcomes research has become increasingly common,
      investigators must be cognizant of the limitations of comorbidity measures
      derived from these data sources in capturing and controlling for differences in
      patient health status. The assessment of comorbidity using claims data is a
      complex and evolving area of investigation.

PMID- 12187166
TI  - Measuring breast, colorectal, and prostate cancer screening with medicare claims
      data.
AB  - BACKGROUND: Evaluating the use and effectiveness of cancer screening is an
      important component of cancer control programs. Medicare claims may be a useful
      source of data when screening older populations, but they are limited in terms of
      completeness and the ability to distinguish screening tests from those provided
      for diagnosis or surveillance. RESEARCH DESIGN: A review of the major screening
      modalities for breast, colorectal, and prostate cancer, Medicare's policies for
      covering these tests, and the procedure codes used to identify them in Medicare
      claims. RESULTS: Although Medicare's coverage has been extended to include
      screening mammography, colonoscopy, sigmoidoscopy, fecal occult blood tests,
      double-contrast barium enema, and prostate-specific antigen tests, providers have
      been slow to adopt the corresponding screening codes. CONCLUSION: Challenges
      persist in measuring screening use, and innovative approaches are required to
      distinguish screening tests from diagnostic and follow-up evaluations.

PMID- 12187167
TI  - Use of SEER-Medicare data for measuring cancer surgery.
AB  - BACKGROUND: The accuracy and completeness of the SEER-Medicare data for measuring
      cancer-related therapy have not been extensively evaluated. OBJECTIVES: To
      investigate the best method for measuring cancer-related surgery among patients
      in the SEER-Medicare database. SUBJECTS: A total of 149,970 incident cases of
      breast, colorectal, endometrial, lung, pancreatic, and prostate cancer diagnosed
      between 1991 and 1993.MEASURES The most invasive surgical procedure identified
      through Medicare's inpatient, physician, and hospital outpatient claims was
      compared with corresponding data from the SEER files. RESULTS: Agreement between
      the SEER and Medicare files was generally highest for resection and radical
      surgery (eg, kappa 0.70-0.90). While there was less agreement regarding no
      surgical therapy and biopsy individually, the concordance of the two sources in
      excluding cancer-directed surgery was high. Compared with inpatient data alone,
      using the combined inpatient, physician, and outpatient data increased
      concordance between SEER and Medicare for less invasive procedures. CONCLUSIONS:
      The agreement of SEER and Medicare data appears to be good for major surgical
      procedures and for excluding persons who did not undergo cancer-directed surgery.
      Both the SEER and the Medicare data captured a small number of surgeries not
      reported in the other file. Therefore, where possible, using both data sources
      will enhance identification of surgeries. Because the analysis was performed with
      linked data, the accuracy of surgical claims in Medicare data alone cannot be
      assessed.

PMID- 12187168
TI  - Studying radiation therapy using SEER-Medicare-linked data.
AB  - BACKGROUND: Numerous studies have used the SEER or Medicare data to assess the
      use of radiation therapy. However, the completeness of these data has not been
      evaluated. METHODS: Using linked SEER-Medicare data, a cohort was created that
      included incident cases of breast, endometrial, lung, prostate, or rectal cancer
      from 1991 to 1996 in persons 65 years and older. For each of these cases, use of
      radiation therapy as an initial course of treatment reported from the SEER data
      was compared with use of radiation therapy in the months following diagnosis, as
      determined from the Medicare claims. RESULTS: Overall, there was a high agreement
      between SEER and Medicare sources for use of radiation therapy. Agreement was 88%
      for lung cancer, 93% for prostate cancer, 94% for rectal and breast cancers, and
      95% for endometrial cancer. Within the Medicare files, radiation claims were
      found in MedPAR Physician Supplier Part B and Outpatient files. CONCLUSIONS:
      There is a high level of agreement between SEER and Medicare reporting of
      radiation treatments after a cancer diagnosis, suggesting that either source can
      be used to assess radiation-related treatment patterns. However, for the most
      complete ascertainment of radiation use, both SEER and Medicare sources should be
      used.

PMID- 12187169
TI  - Utility of the SEER-Medicare data to identify chemotherapy use.
AB  - BACKGROUND: Medicare claims include codes for chemotherapy administration and
      specific drugs given, and researchers are increasingly using these data to
      measure the use of chemotherapy. However, the validity and completeness of these
      data as a source of information has not been established. OBJECTIVES: This
      analysis is intended to assess the utility of the Medicare claims to capture
      chemotherapy use. METHODS: Persons with breast, colorectal, and ovarian cancer
      were identified from the linked SEER-Medicare data. Their Medicare claims were
      reviewed to determine if there were any bills for chemotherapy, and if so, if
      there were claims for specific agents. This information was compared with data on
      the first course of treatment obtained from hospitals and treating physicians by
      the SEER registries through an NCI-supported Patterns of Care Studies (POC).
      Agreement was measured using kappa statistics. The sensitivity of the Medicare
      claims to capture chemotherapy, as reported from the POC data, was also measured.
      An additional comparison assessed the agreement between the two data sources
      concerning which specific drugs had been given. RESULTS: For all of the cancers,
      there was a high level of agreement between the Medicare claims and the POC data
      regarding whether or not the patient had received chemotherapy (kappa >or=0.73).
      The sensitivity of the Medicare data to determine if a person had received
      chemotherapy was high (>or=88%). In cases where the Medicare claim included a
      code for a specific drug, there high agreement between Medicare and POC about the
      specific drug given in breast and colorectal cancers, although the agreement was
      lower for ovarian cancers. The sensitivity of the Medicare claims to identify
      specific agents varies by cancer type. CONCLUSIONS: The Medicare claims can be
      used to identify which persons are receiving chemotherapy. The utility of
      Medicare data to measure treatment with specific agents varies by cancer type and
      specific agent. For some cancers, it is possible to use these claims to assess
      use of specific drugs, while for other drugs the data are limited.

PMID- 12187170
TI  - Measuring complications of cancer treatment using the SEER-Medicare data.
AB  - BACKGROUND: The linkage of SEER registry data with Medicare claims allows the
      longitudinal tracking of health care and outcomes for patients after a cancer
      diagnosis. One category of outcomes amenable to research using Medicare claims is
      complications of cancer treatments: the unintentional, adverse side effects or
      sequelae of interventions used to treat or palliate cancer patients. RESEARCH
      DESIGN: The authors review some of the methods and limitations of using Medicare
      claims to identify both acute and chronic complications of cancer treatments, and
      present an original analysis comparing survey-based and claims-based
      complications following radical prostatectomy for prostate cancer to illustrate
      some of the potential limitations inherent in using claims for this purpose.
      RESULTS: Utility of the Medicare claims for identifying postdischarge
      complications varies by the patient type, the initial treatment used, and any
      subsequent treatment of complications. For patients undergoing surgical
      interventions, Medicare claims can be used to identify most acute inpatient
      complications. However, claims data cannot be used as effectively in the long
      term to capture chronic complications, particularly when the complication does
      not consistently prompt an intervention. CONCLUSION: Researchers who use the SEER
      Medicare-linked database to assess long-term complications of cancer treatments
      should exercise caution when designing and interpreting studies. Ideally, for
      studies of most chronic complications of cancer care, validation studies similar
      to the one performed here would provide valuable additional evidence to assess
      the credibility of conclusions based on claims data.

PMID- 12187171
TI  - Methodological issues in the use of administrative claims data to study
      surveillance after cancer treatment.
AB  - BACKGROUND: Administrative claims databases linked to tumor registry data provide
      an excellent opportunity for studying the follow-up care of cancer patients.
      RESEARCH DESIGN: Methodological principles of study design are reviewed, using
      examples drawn from the recently published literature. RESULTS: Most follow-up
      care is outpatient-based. Therefore, in studies using Medicare claims, the
      patient should be eligible for Medicare Part B and should not be enrolled in a
      Medicare HMO. In studies of surveillance testing, it may be appropriate to
      exclude subjects who are near death, in a hospice, or in whom a new or recurrent
      cancer develops. The definition of the period for measurements of surveillance
      testing requires consideration, as does periodicity in patterns of testing.
      Several analytic methods can be employed, from proportions undergoing testing to
      survival analysis methods. Measurement of 'surveillance tests' among control
      subjects (those without cancer) may be useful for comparison with cancer
      patients. To date, administrative claims data have been most useful in studies
      investigating the quality of, and disparities in, cancer care. CONCLUSION: With
      appropriate attention to methodological issues, linked tumor registry and
      administrative databases can provide important insights into the quality of
      survivorship care for cancer.

PMID- 12187172
TI  - Identifying cancer relapse using SEER-Medicare data.
AB  - INTRODUCTION: Tumor registries capture valid information at the time of cancer
      diagnosis, but often do not conduct longitudinal follow-up evaluations. However,
      investigators may be interested in questions relating to subsequent relapsed
      disease. Linking administrative data to registry data, as in the creation of the
      SEER (Surveillance, Epidemiology, and End Results) and Medicare data set, can
      provide the ability to infer the occurrence of relapse in selected situations.
      METHODS: The authors created different algorithms to detect relapse of acute
      myelogenous leukemia (AML). A retrospective cohort of patients with AML was
      identified, and both their billing data and medical records were obtained. The
      algorithms were then applied to the billing data, the results were compared with
      medical record review. RESULTS: Eighty-nine patients were identified, of whom 22
      were treated for relapsed AML. The sensitivity of the best algorithm for
      detecting relapse was 86%, and the specificity 99%, with a positive predictive
      value of 95% and a negative predictive value of 96%. CONCLUSIONS: Identification
      of relapse from SEER-Medicare data using clinical algorithms is feasible for
      cancers where a majority of patients receive treatment for relapse, without a
      "watch and wait" strategy, and where that treatment is with a modality that can
      be detected in billing data (ie, intravenous chemotherapy, radiation, surgery, or
      all three). Optimal analytic situations are ones in which the investigator is
      mostly interested in positive predictive value, less interested in sensitivity,
      and wants to evaluate outcomes among those patients who receive treatment for
      their relapsed disease. However, the accuracy of such an approach for cancers
      other than AML has not yet been established.

PMID- 12187173
TI  - Linking physician characteristics and medicare claims data: issues in data
      availability, quality, and measurement.
AB  - BACKGROUND: Increasingly, investigators are using administrative databases to
      answer research questions requiring physician characteristics information. This
      article provides a roadmap for investigators who use Medicare data to answer such
      questions, focusing on use of the Surveillance, Epidemiology, and End Results
      (SEER)-Medicare files. METHODS: Three data sources that can be linked to identify
      physician characteristics-Medicare claims, the Unique Physician Identification
      Number (UPIN) Registry, and the American Medical Association (AMA) Masterfile
      were examined for data availability, linkage rates, and quality. These databases
      also were used to explore measurement issues regarding physician specialty and
      practice volume. RESULTS: Over 98 percent of UPINs identified from the Medicare
      claims could be linked with both the AMA Masterfile and the UPIN Registry. The
      AMA Masterfile is the best source of sociodemographic and medical training
      information; the Medicare claims are the best source of practice ZIP code; and
      the UPIN Registry is the best source of practice organization data. The
      operationalization of variables such as physician specialty and practice volume
      is dependent on the specific research question that is being addressed.
      CONCLUSION: Administrative databases, such as SEER-Medicare data linked to AMA
      Masterfile or UPIN Registry data, are an important resource for investigators
      interested in assessing the relationship between physicians' personal and
      practice characteristics and the content or outcomes of clinical care.

PMID- 12187174
TI  - Identifying and measuring hospital characteristics using the SEER-Medicare data
      and other claims-based sources.
AB  - The context in which health care is delivered may have an impact on the outcomes
      and processes of care. Researchers analyzing claims data that reflect care
      rendered at many institutions may wish to identify hospital characteristics such
      as bed size, teaching status, degree of specialization, and case volume to
      evaluate their influence on outcomes. The authors describe the resources
      available from administrative data for characterizing hospitals. The article
      focuses on analyses using the SEER-Medicare-linked data, but has direct relevance
      for investigators working with other sources of claims data. First, the authors
      focus on assessment of hospital case volume, which is the principal hospital
      attribute that can be obtained directly from the SEER-Medicare data files.
      Second, they assess the information regarding hospital characteristics that can
      be gleaned from the American Hospital Association (AHA) survey and the annual
      cost reports submitted to the Center for Medicare and Medicaid Services (CMS) by
      all certified hospitals. From a comparison of the responses of 4,434 hospitals to
      1994 AHA and CMS surveys, the authors conclude that the two data sources contain
      very similar information, but that for most investigators, use of data from CMS
      cost reports will be preferable to use of AHA data because of higher survey
      completion rates and public availability.

PMID- 12187175
TI  - Estimating health care costs related to cancer treatment from SEER-Medicare data.
AB  - BACKGROUND: Cancer-specific medical care costs are used by health service
      researchers, medical decision analysts, and health care policymakers. The SEER
      Medicare database is a unique data resource that makes it possible to derive
      incidence- and prevalence-based estimates of cancer-related medical care costs by
      site and stage of disease, by treatment approach, and for age and gender strata
      for individuals older than 65 years. OBJECTIVES: This paper describes the cost
      related data available in the SEER-Medicare database, and discusses techniques
      and methods that have been used to derive various cost estimates from these data.
      The limitations of SEER-Medicare data as a source of cost estimates are also
      discussed. RESULTS: Examples of cost estimates for colorectal and breast cancer
      derived from SEER-Medicare are presented, including estimates of incidence-based
      cost (average cost per patient) by the initial, terminal, and continuing care
      phases of cancer treatment. Estimates of cancer-related treatment costs, costs by
      type of treatment, and long-term costs are presented, as are prevalence-based
      costs (aggregate Medicare and national expenditures) by cancer type.

PMID- 12187176
TI  - Efforts to better understand pharmaceutical use, costs, and outcome.

PMID- 12187177
TI  - Pharmacy data identify poorly adherent patients with schizophrenia at increased
      risk for admission.
AB  - BACKGROUND: Health care organizations may be able to use pharmacy data to
      identify patients with schizophrenia and poor antipsychotic adherence. OBJECTIVE:
      To determine whether a pharmacy-based measure of outpatient adherence, the
      medication possession ratio (MPR), is associated with adverse outcomes among
      patients with schizophrenia, as evidenced by increased psychiatric admission.
      RESEARCH DESIGN: Cohort study linking pharmacy and utilization data for veterans
      with schizophrenia. MPRs were calculated by dividing the number of days' supply
      of antipsychotic medication the veteran had received by the number of days'
      supply they needed to receive to take their antipsychotic continuously. Using
      multivariate regression, the relationship between MPRs and psychiatric admission
      was examined. SUBJECTS: Sixty-seven thousand seventy-nine veterans who received a
      diagnosis of schizophrenia and had outpatient antipsychotic medication fills
      between October 1, 1998 and September 30, 1999. RESULTS: Patients with MPRs close
      to 1.0 had the lowest rates of admission. As patients secured progressively
      smaller proportions of required antipsychotic medication (and had smaller MPRs),
      rates of admission climbed. Among patients on one antipsychotic (n = 49,003),
      patients with poor adherence (MPRs < 0.8) were 2.4 times as likely to be admitted
      as patients with good adherence (MPRs from 0.8-1.1). 23% of poorly adherent
      patients but only 10% of adherent patients were admitted. Once admitted, poorly
      adherent patients had more hospital days. Patients who received excess medication
      also had higher admission rates. CONCLUSIONS: Many health care systems may be
      able to use pharmacy data to identify poorly adherent patients with
      schizophrenia. These patients are at-risk for admission and may benefit from
      intervention.

PMID- 12187178
TI  - Health services utilization with reference drug pricing of histamine(2) receptor
      antagonists in British Columbia elderly.
AB  - BACKGROUND: In October 1995, British Columbia introduced a reference pricing
      policy for five therapeutic classes of drugs, including histamine(2) receptor
      antagonists (H(2)RAs), for beneficiaries of its prescription drug program,
      Pharmacare. OBJECTIVES: To evaluate utilization trends in consumption of health
      services in a cohort of Pharmacare beneficiaries to determine if a worsening of
      health outcomes could be detected after implementation of the reference pricing
      policy. RESEARCH DESIGN: Two cohorts, "control" (21 months before the reference
      pricing policy) and "exposed" (at risk for policy effects), were followed for 21
      months. Using a longitudinal generalized linear model (Poisson), and controlling
      for age, sex, and prescriptions in unique drug classes, trend lines in each of
      these time series were compared for 3 periods: 9 months before policy
      implementation (or corresponding index date in the control cohort), 6 months
      after policy implementation, and a subsequent 6-month period. SUBJECTS: Two
      cohorts, each of size 10,000, were constructed by randomly sampling the
      population of Pharmacare beneficiaries exposed to H(2)RAs and other antisecretory
      drugs for 1993 through 1996. MEASURES: Prescriptions, physician office visits and
      associated transactions (ie, laboratory tests), emergency room visits,
      hospitalizations, hospital length of stay, and vital statistics. RESULTS:
      Differences between periods and between cohorts for health services utilization
      were not significant or decreased after imposition of the reference pricing
      policy. CONCLUSION: For these measures, there has been no worsening of health
      outcomes associated with implementing the reference pricing policy.

PMID- 12187179
TI  - Quantifying the physician contribution to managed care pharmacy expenses: a
      random effects approach.
AB  - BACKGROUND: Despite the availability of more sophisticated techniques, few
      alternatives to ordinary least squares (OLS) regression have been utilized to
      profile physician prescribing in managed care. It is not known to what extent the
      modest R values derived from OLS models reflect incomplete risk adjustment or
      widely varying physician prescribing patterns. OBJECTIVES: To quantify the role
      of interphysician variability relative to overall variability in managed care
      pharmacy expenses, and to examine the extent to which different statistical
      approaches generate meaningful differences in profile results. RESEARCH DESIGN:
      Comparison of three basic statistical modeling approaches: OLS, fixed effects
      regression, and random effects (ie, hierarchical) regression models. SETTING: Two
      managed care populations that differed more than 2-fold in per member pharmacy
      expenditures in 1999, one from the Midwestern United States, the other from three
      Western States. MAIN OUTCOME MEASURES: The intraclass correlation coefficient
      (ICC, the proportion of variability in expenses attributable to differences among
      physicians) and the range of projected expenses attributed to each physician's
      prescribing style. RESULTS: The ICCs were small for aggregated pharmacy
      expenditures, 0.04 or less in both populations. As determined by OLS, the most
      costly physician contributed 94,399 U.S. dollars in excess expenses to the
      organization whereas the most parsimonious saved 89,940 U.S. dollars. When
      derived from random effects models, the range in performance was 63% of that
      derived from OLS. CONCLUSIONS: In the populations studied, systematic prescribing
      differences among physicians were small relative to the overall variability in
      pharmacy expenses, suggesting other factors were more likely driving these costs.
      Random effects models generated smaller estimates of the individual physicians'
      contribution to costs, sometimes considerably, relative to those derived from OLS
      and fixed effects approaches.

PMID- 12187180
TI  - Exploring generic drug use behavior: the role of prescribers and pharmacists in
      the opportunity for generic drug use and generic substitution.
AB  - OBJECTIVES: The first objective of this study was to examine the prevalence of
      prescriptions that offer the opportunity for generic drug use (a prescription for
      a multisource drug product). The second objective was to examine the prevalence
      of generic drug use by examining the rate of generic drug prescribing for
      multisource drug products and the rate of generic substitution by pharmacists.
      The last objective was to examine the association of prescriber, pharmacist,
      insurance, patient, and drug variables with the prescribing of drugs allowing the
      opportunity for generic drug use and generic substitution. RESEARCH DESIGN: A
      database containing information for 6380 prescription orders was used for
      analysis. MEASURES: Random-effects logistic regression panel data estimation was
      used to examine the association of independent variables with whether a
      prescription allowed the opportunity for generic drug use and whether a
      prescription allowing generic drug use and written using the brand name was
      generically substituted. RESULTS: The opportunity for generic drug use existed
      for 63% of prescription orders. Prescriptions covered by private third party and
      indemnity insurance were 33% (97.5% CI, 0.56-0.80), and 21% (97.5% CI, 0.62
      0.98), less likely, respectively, to allow the opportunity for generic drug use
      relative to uninsured prescriptions. Unobserved prescriber characteristics
      accounted for 23% (95% CI, 0.14-0.34) of the variance in the opportunity for
      generic drug use. Pharmacists generically substituted 83.8% of prescriptions that
      could be generically substituted. Prescriptions covered by Medicaid were 4.57
      (97.5% CI, 2.83-7.39), 5.15 (97.5% CI, 3.25-8.13), and 4.85 (97.5% CI, 2.83-8.17)
      times more likely, respectively, to be generically substituted relative to
      uninsured, private third party and indemnity prescriptions. Unobserved
      characteristics of pharmacists accounted for 44% (95% CI, 0.33-0.55) of the
      variance in the occurrence of generic substitution. CONCLUSIONS: Pharmacists play
      a large and important role in generic drug use and efforts to increase generic
      drug use directed at pharmacists should be maintained. Additional efforts to
      increase generic drug use likely should be targeted at prescribers.

PMID- 12187181
TI  - Validity of information on comorbidity derived rom ICD-9-CCM administrative data.
AB  - BACKGROUND: The comorbidity variables that constitute the Charlson index are
      widely used in health care research using administrative data. However, little is
      known about the validity of administrative data in these comorbidities. The
      agreement between administrative hospital discharge data and chart data for the
      recording of information on comorbidity was evaluated. The predictive ability of
      comorbidity information in the two data sets for predicting in-hospital mortality
      was also compared. METHODS: One thousand two hundred administrative hospital
      discharge records were randomly selected in the region of Calgary, Alberta,
      Canada in 1996 and used a published coding algorithm to define the 17
      comorbidities that constitute the Charlson index. Corresponding patient charts
      for the selected records were reviewed as the "criterion standard" against which
      validity of the administrative data were judged. RESULTS: Compared with the chart
      data, administrative data had a lower prevalence in 10 comorbidities, a higher
      prevalence in 3 and a similar prevalence in 4. The kappa values ranged from a
      high of 0.87 to a low of 0.34; agreement was therefore near perfect for one
      variable, substantial for six, moderate for nine, and only fair for one variable.
      For the Charlson index score ranging from 0 to 5 to 6 or higher, agreement was
      moderate to substantial (kappa = 0.56, weighted kappa = 0.71). When 16 Charlson
      comorbidities from administrative data were used to predict in-hospital
      mortality, 10 comorbidities and the index scores defined using administrative
      data yielded odds ratios that were similar to those derived from chart data. The
      remaining six comorbidities yielded odds ratios that were quite different from
      those derived from chart data. CONCLUSIONS: Administrative data generally agree
      with patient chart data for recording of comorbidities although comorbidities
      tend to be under-reported in administrative data. The ability to predict in
      hospital mortality is less reliable for some of the individual comorbidities than
      it is for the summarized Charlson index scores in administrative data.

PMID- 12187182
TI  - Effects of provider networks on health care costs for workers with short-term
      injuries.
AB  - OBJECTIVES: This study examines the effects of preferred provider networks on
      health care costs and service utilization in the treatment of work-related
      injuries. RESEARCH DESIGN: A retrospective comparison of workers' compensation
      claims treated by network and non-network providers was conducted. Pairwise
      matches of individual cases are used to control for differences in case mix and
      severity of injury between network patients and a non-network comparison group.
      Cost differentials are separated into a price effect, the difference in costs
      attributed to network price discounts, holding services constant; and a
      utilization effect, the difference in costs attributed to differences in service
      utilization, holding prices constant. SUBJECTS: Data include approximately 87,000
      workers' compensation claims, from California, Connecticut, and Texas, with
      injury dates between 1995 and 1997. The samples are restricted to five common
      injury types and work absences of less than 7 days. Workers treated solely by
      network providers are compared with a matched group of workers treated solely by
      non-network providers. RESULTS: Average health care costs are lower for network
      claims than for matched non-network claims. Price discounts explain a large part
      of the cost differentials for all injury groups studied, but differences in
      service utilization are also important for back cases and cumulative stress
      injuries. CONCLUSIONS: Networks bring the traditionally high costs of health care
      for work-related injuries closer to the costs of health care for off-the-job
      injuries. The network savings primarily reflect price discounts for the same
      services, thereby representing an increase in the cost-effectiveness of care.

PMID- 12187183
TI  - Understanding the causal relationship between patient-reported interpersonal and
      technical quality of care for depression.
AB  - OBJECTIVES: Patient ratings of their health care experience have become
      increasingly important as indicators of interpersonal quality of care. Currently
      the link between technical and interpersonal quality of care indicators is not
      well understood. The goal of this study was to examine the temporal relationship
      between technical quality of care for depression and interpersonal quality of
      care by examining their association over time. METHODS: A cross-lagged
      (longitudinal) path analytic model was estimated to examine the causal
      relationship between two measures of interpersonal quality of care and technical
      quality of care among 697 respondents participating in the 18 and 24 month
      assessments of Partners in Care (PIC). Measures of age, gender, number of chronic
      diseases, indicators of anxiety and depression, recent service utilization, and
      stability of the doctor-patient relationship were included as covariates.
      RESULTS: After controlling for study design and relevant patient characteristics,
      one significant cross-lagged effect was found: that from one measure of
      interpersonal quality (patient satisfaction) to technical quality (standardized
      coefficient = 0.18), but not from quality to satisfaction. CONCLUSION: Results of
      these analyses indicate that patients who report high satisfaction with care are
      more likely to receive higher technical quality depression care 6 months later as
      compared with those who are less satisfied. This implies that one pathway to
      improving technical quality of care may be through increasing patients'
      satisfaction.

PMID- 12187184
TI  - Cost-effectiveness and choice of infant transport systems.
AB  - OBJECTIVE: To compare cost-effectiveness of three types of infant transport
      models (Emergency Medical Technicians [EMT], Registered Nurses [RN], or Combined
      Teams [CT] of RNs and Respiratory Therapists) and to derive a decision model to
      guide choice of a transport system. RESEARCH DESIGN: A prospective, multicenter,
      observational study was conducted to compare infant physiologic status before and
      after transport. Cost-effectiveness analysis from the perspective of the third
      party payer, sensitivity analysis and threshold analysis were performed.
      SUBJECTS: All (n = 1931) out born infants with complete transport data admitted
      to 11 regional tertiary-level Canadian NICUs from January 1996 to October 1997.
      MEASURES: Change in Transport Risk Index of Physiologic Stability (TRIPS) Score
      before and after transport, transport costs. RESULTS: Change in TRIPS was
      predicted by gestational age at transport, transport duration, and pretransport
      TRIPS score, but not the type (EMT, RN, CT) of transport team, mode (air/ground)
      or direction (forward/retrograde) of transport, presence of a physician, and
      other baseline population risks (sex, small for gestational age, antenatal
      corticosteroid treatment, Apgar score). The RN model is least costly under most
      assumptions. At high transport volumes (>2760 transports per year) and long
      average transport times (>6.8 h per transport), the EMT model was less costly.
      Cost drivers of transport were volume of transport, relative wages of transport
      personnel, and percent of waiting time dedicated to infant transport.
      CONCLUSIONS: A deterministic decision-analytic model can be used to model
      transport cost-effectiveness and derive a threshold analytic chart for
      identifying the least costly transport model.

PMID- 12187185
TI  - Effect of patient socioeconomic status on physician profiles for prevention,
      disease management, and diagnostic testing costs.
AB  - BACKGROUND: Previous research shows patient socioeconomic status (SES) affects
      physician profiles for health status and satisfaction, but effects on other
      aspects of care are not known. OBJECTIVE: To examine the effect of patient SES on
      physician profiles for preventive care, disease management, and diagnostic
      testing costs. RESEARCH DESIGN: Cross-sectional analysis of a managed care claims
      data. SUBJECTS: Five hundred sixty-eight physicians and 600,618 patients.
      MEASURES: Patient age, gender, case-mix, and SES based on zip code, likelihood of
      having a Papanicolaou smear, mammogram, for diabetics having had a glycosylated
      hemoglobin, diabetic eye exam, and diagnostic testing costs. RESULTS: For each
      performance indicator, except glycosylated hemoglobin, there was a statistically
      significant effect of adjusting for patient SES. For diabetic eye checks,
      mammograms and Papanicolaou tests respectively, 5%, 16%, and 21% of physicians
      who were outliers (in the top or bottom 5% of rankings) were no longer outliers
      after socioeconomic adjustment. For all performance measures the change in
      physician ranking was strongly correlated with the mean practice SES.
      CONCLUSIONS: Patient SES, as measured by zip code, appreciably affects physician
      profiles for preventive care and diabetes management. Monitoring patient SES
      using patient zip codes could be used to target resources to improve outcomes for
      higher risk patients.

PMID- 12187189
TI  - Hereditary prostate cancer: clinical aspects.
AB  - PURPOSE: We review the current epidemiological and genetic knowledge regarding
      hereditary prostate cancer, and outline its clinical implications. MATERIALS AND
      METHODS: Published articles on hereditary prostate cancer were identified using
      the MEDLINE data base. RESULTS: A risk of prostate cancer, particularly early
      onset disease, is strongly affected by family history (number of relatives with
      prostate cancer and their age at diagnosis). A family history of prostate cancer
      increases the positive predictive value of prostate specific antigen testing and,
      hence, heredity should always be assessed when deciding whether to perform
      biopsies in a man with a prostate specific antigen level of 3 to 10 ng./ml.
      Epidemiological studies indicate that dominantly inherited susceptibility genes
      with high penetrance cause 5% to 10% of all prostate cancer cases, and as much as
      30% to 40% of early onset disease. More than a half dozen chromosome loci that
      may comprise such genes have been mapped, but as of May 2002 no prostate cancer
      susceptibility gene of major importance had been cloned. Most likely,
      environmental factors and comparatively common variants of several other genes
      affect prostate cancer risk in families with or without multiple cases of the
      disease. On average, hereditary prostate cancer is diagnosed 6 to 7 years earlier
      than sporadic prostate cancer, but does not otherwise differ clinically from the
      sporadic form. As a consequence of the earlier onset, a greater proportion of men
      with hereditary prostate cancer die of the disease than those with nonhereditary
      prostate cancer. At present, the only clinically applicable measure to reduce
      prostate cancer mortality in families with hereditary disease is screening, with
      the aim of diagnosing the disease when it is still in a curable stage.
      CONCLUSIONS: Hereditary susceptibility is now considered the strongest risk
      factor for prostate cancer and has profound clinical importance. The genetic
      mechanism behind such susceptibility has turned out to be more complex than
      initially thought, and will probably not be completely understood for many years
      to come.

PMID- 12187188
TI  - Quality of life assessment in men and women with urinary incontinence.
AB  - PURPOSE: The literature on assessment of quality of life from 1993 to 2001 was
      reviewed to evaluate and compare existing measures through their psychometric
      value and make adequate recommendations on their clinical use and future
      research. MATERIALS AND METHODS: We selected quality of life articles and
      abstracts from Current Content 1996 to 1997 and MEDLINE 1993 to 1996 for our
      first report presented at the first consultation on incontinence in Monaco in
      1998. This report was then updated up to September 2001 using the same strategy.
      We made our recommendations based on our clinical and research experience with
      these tools. RESULTS: Several quality of life generic or disease specific
      questionnaires have been published for male and female urinary incontinence.
      However, their psychometric value is far from uniform and for most of them
      responsiveness is weak or has never been reported. CONCLUSIONS: Few quality of
      life questionnaires are at an advanced enough stage of development to be applied
      in clinical practice. However, even with these questionnaires more study remains
      to be done to make them shorter, sometimes even more specific and easier to use
      in different populations.

PMID- 12187190
TI  - The early diagnosis and radical cure of carcinoma of the prostate. Being a study
      of 40 cases and presentation of a radical operation which was carried out in four
      cases. 1905.

PMID- 12187191
TI  - Robustness of free prostate specific antigen measurements to reduce unnecessary
      biopsies in the 2.6 to 4.0 ng./ml. range.
AB  - PURPOSE: Prostate specific antigen (PSA) cutoffs lower than 4.0 ng./ml. are being
      evaluated more frequently but lower PSA cutoffs increase the number of prostatic
      biopsies. PSA exists in several forms free and complexed to proteins. Percent
      free PSA is lower in men with prostate cancer. Accordingly, free PSA and
      complexed PSA have been used to distinguish between cancer and benign disease in
      the diagnostic gray zone of 4 to 10 ng./ml. to eliminate unnecessary biopsies.
      There are limited data on the robustness of free PSA measurements in the 2.6 to
      4.0 ng./ml. total PSA range. MATERIALS AND METHODS: We evaluated percent free PSA
      measurements to discriminate between cancer and benign conditions in 965
      consecutive volunteers in a prostate cancer screening study who underwent
      prostatic biopsy for a PSA of 2.6 to 4.0 ng./ml. and had benign digital rectal
      examination. RESULTS: Overall 25% of men had cancer detected. A 25% free PSA
      cutoff detected 85% of cancers and avoided 19% of negative (cancer-free)
      biopsies, while a 30% free PSA cutoff detected 93% of cancers and avoided only 9%
      of negative biopsies. Of those men who underwent radical prostatectomy 132 (80%)
      had pathologically organ confined tumors. Only 5% of these tumors fulfilled the
      published pathological criteria for possibly clinically unimportant tumors.
      CONCLUSIONS: Percent free PSA provides risk assessment but does not eliminate
      many unnecessary prostatic biopsies while maintaining a high sensitivity in the
      narrow total PSA range of 2.6 to 4.0 ng./ml.

PMID- 12187192
TI  - Comparing Taguchi and Lich-Gregoir ureterovesical reimplantation techniques for
      kidney transplants.
AB  - PURPOSE: We compared the incidence of urological and anastomotic complications,
      and the duration of ureteral reimplantation for the Taguchi and Lich-Gregoir
      techniques. MATERIALS AND METHODS: We recorded all urological and anastomotic
      complications that developed from the date of transplantation through December
      31, 2001. The cutoff date for transplantation was August 30, 2000. The urological
      complications evaluated included complicated hematuria, urinary fistula, ureteral
      stenosis, symptomatic vesicoureteral reflux and operative time. The chi-square
      test was done to compare the proportion of complications in the groups and the
      Mann Whitney test was used to compare the duration of ureteral reimplantation.
      RESULTS: Of the 575 transplants evaluated 416 and 159 were performed via the Lich
      Gregoir and Taguchi techniques, respectively. The incidence of anastomotic
      complications was 10.7%. Complications in the Lich-Gregoir group included fistula
      in 4.7% of cases, stenosis in 4.1%, symptomatic vesicoureteral reflux in 1.9% and
      complicated hematuria in 0.5%. Complications in the Taguchi group included
      urinary fistula in 6.3% of cases, stenosis in 2.5% and complicated hematuria in
      2.5%. Symptomatic reflux was not observed in this group. There was a higher
      proportion of hematuria at the limit of statistical significance in the Taguchi
      group (p = 0.05). There were a higher number of urological complications in
      transplants from live donors in the Lich-Gregoir group (p = 0.01), mostly
      involving fistula (p = 0.05). There were no significant differences in the groups
      in overall complications. Average operative time for the Taguchi and Lich-Gregoir
      techniques was 14.2 and 29 minutes, respectively. This difference was significant
      (p = 0.02). CONCLUSIONS: In the sample studied Taguchi ureterocystoneostomy
      proved to be a more rapid method without increasing the incidence of urological
      or anastomotic complications. There were no cases of symptomatic reflux in the
      Taguchi group and select fistula cases could be managed conservatively. The Lich
      Gregoir cohort was at greater risk for the urological complications of live donor
      transplantation. The Taguchi method has become the ureterovesical reimplantation
      technique of choice in our setting.

PMID- 12187193
TI  - Effects of 5 different diets on urinary risk factors for calcium oxalate kidney
      stone formation: evidence of different renal handling mechanisms in different
      race groups.
AB  - PURPOSE: Since the incidence of renal calculi in the South African black
      population is extremely rare while in white subjects it occurs at the same rate
      as elsewhere in the western world, we investigated the possibility that different
      renal handling mechanisms in response to different dietary challenges might occur
      in the 2 race groups. MATERIALS AND METHODS: We administered 5 different dietary
      protocols, including low calcium, high oxalate, vitamin C, high salt and lacto
      vegetarian, to 10 healthy male subjects from each race group. We collected 24
      hour urine at baseline and after 4 days on the prescribed diet which were
      analyzed for biochemical and physicochemical risk factors. Dietary intake was
      controlled throughout the experimental period. A 24-hour dietary recall
      questionnaire was recorded at baseline and analyzed using food composition
      tables. Statistical analysis of variance was performed on all the data. RESULTS:
      The low calcium diet caused statistically significant changes only in black
      subjects, which consisted of urinary oxalate increase (0.17 to 0.23 mmol./24
      hours, p = 0.01), relative supersaturation of calcium oxalate decrease (1.88 to
      0.97, p = 0.03) and relative supersaturation of brushite increase (0.85 to 1.69,
      p = 0.03). The high oxalate diet caused statistically significant changes in both
      race groups but these changes were different in the 2 groups. In white subjects
      urinary pH increased (6.24 to 6.62, p = 0.01), potassium excretion increased
      (40.01 to 73.49, p = 0.01) and relative supersaturation of brushite increased
      (1.34 to 2.12, p = 0.05). In black subjects urinary citrate increased (1.94 to
      2.99 mmol./24 hours, p = 0.01). Clinically unimportant changes occurred in both
      race groups after the other 3 diets. CONCLUSIONS: Renal handling of dietary
      calcium and oxalate in South African black and white subjects is different and
      may explain the different stone incidence in the 2 race groups.

PMID- 12187194
TI  - When is medical prophylaxis cost-effective for recurrent calcium stones?
AB  - PURPOSE: Medical management is generally recommended for recurrent calcium stones
      to prevent future episodes. However, in this era of extracorporeal shock wave
      lithotripsy and outpatient ureteroscopy it is not known whether medical
      prophylaxis is more cost-effective than treatment of recurrent stone episodes.
      The cost of medical prophylaxis was compared with the cost of clinically managing
      recurrent stone episodes, and the stone recurrence rate without prophylaxis
      (stone frequency) at which these 2 treatment approaches became cost equivalent
      was determined. MATERIALS AND METHODS: An international cost survey was conducted
      in 10 countries to compare costs of medical prophylaxis and managing recurrent
      acute stone episodes. Costs of an acute stone episode included an emergency room
      visit, associated radiographic imaging to confirm diagnosis of a symptomatic
      stone and outpatient treatment of upper urinary tract stones that did not pass
      spontaneously. Costs of medical management included an initial limited metabolic
      evaluation, drug therapy, a followup office visit every 6 months that included a
      24-hour urinalysis and radiographic imaging of the kidneys, ureters and bladder
      once a year. RESULTS: Costs of medical prophylaxis and managing an acute stone
      episode varied significantly from country to country. The stone frequency at
      which costs of these management options became equivalent ranged from 0.3 to 4
      stone episodes a year. CONCLUSIONS: Medical management of a first stone episode
      is not cost-effective. Cost analysis should be individualized for specific health
      care plans to determine which practice patterns are most cost-effective for a
      particular patient with recurrent calcium stone formation.

PMID- 12187195
TI  - Manual specimen retrieval without a pneumoperitoneum preserving device for
      laparoscopic live donor nephrectomy.
AB  - PURPOSE: We present a novel method of kidney retrieval based on a modified
      Pfannenstiel incision and insertion of the assistant hand into the abdominal
      cavity without a device for pneumoperitoneum preservation. This maneuver is
      performed as the last step in pure laparoscopic live donor nephrectomy. Also, we
      assessed the effect of this technique on warm ischemia time compared with the
      standard laparoscopic bag retrieval technique. MATERIALS AND METHODS: A total of
      70 laparoscopic live donor nephrectomies were performed at our institutions
      between October 1998 and March 2001. The first 43 cases were completed using an
      EndoCatch bag device (Auto Suture, Norwalk, Connecticut) for specimen retrieval,
      while the last 27 were done using a novel manual retrieval technique through a
      modified Pfannenstiel incision. We retrospectively analyzed the results in regard
      to warm ischemia time and intraoperative complications related to the procedure.
      RESULTS: A statistically significant difference was noted in the EndoCatch and
      manual retrieval groups in regard to warm ischemia time (p <0.001). There were 2
      complications related to the EndoCatch device and none related to the manual
      technique. No differences were detected regarding recipient outcomes.
      CONCLUSIONS: Manual specimen retrieval after live donor nephrectomy allows
      shorter warm ischemia time, while saving the cost of an EndoCatch bag or
      pneumoperitoneum preserving device that would be used during hand assisted live
      donor nephrectomy. It was shown to be a safe method without increased donor
      morbidity.

PMID- 12187196
TI  - Laparoscopic and robot assisted radical prostatectomy: establishment of a
      structured program and preliminary analysis of outcomes.
AB  - PURPOSE: The technique of laparoscopic radical prostatectomy is difficult to
      master and is associated with a steep learning curve. We hypothesized that a
      structured approach to establishing a laparoscopic prostatectomy program would
      diminish complications during the learning process and that robotic technology
      would be useful in learning the operation. MATERIALS AND METHODS: A structured
      laparoscopic radical prostatectomy program was introduced at the Vattikuti
      Urology Institute on October 23, 2000. One of 2 surgeons with a combined
      experience of more than 500 laparoscopic radical prostatectomies performed or
      supervised the first prostatectomies, training a third surgeon with extensive
      "open" surgical skills but no laparoscopic experience. The "trained" surgeon then
      started performing the operation independently with robotic assistance. The
      results of this approach were analyzed at the end of 12 months. RESULTS: We
      performed 48 laparoscopic radical prostatectomies and 50 robot assisted
      prostatectomies within the 12-month period. The preoperative and intraoperative
      demographical variables were comparable in both groups as were the operative
      times, changes in hemoglobin concentrations, durations of hospitalization,
      positive margin rates and overall complication rates. All measured parameters
      were comparable to the "best-in-class" values for laparoscopic radical
      prostatectomy reported in the literature. CONCLUSIONS: A structured approach
      minimizes complications during the establishment of laparoscopic radical
      prostatectomy program. Robotic assistance helps skilled "open" surgeons learn the
      technique of laparoscopic radical prostatectomy.

PMID- 12187197
TI  - Unclassified renal cell carcinoma: clinical features and prognostic impact of a
      new histological subtype.
AB  - PURPOSE: We characterized the histopathological features and clinical behavior of
      unclassified renal cell carcinoma and compared the prognostic outcome in patients
      with unclassified and conventional (clear cell) renal cell carcinoma. MATERIALS
      AND METHODS: A total of 31 patients with unclassified renal cell carcinoma are
      included in the kidney cancer database at our institution. Another 317 matched
      patients with clear cell carcinoma were used for comparing demographic, clinical,
      pathological and survival data. RESULTS: The incidence of unclassified renal cell
      carcinoma was 2.9%. At initial diagnosis 29 patients (94%) with unclassified and
      264 (83%) with clear cell renal cell carcinoma had metastatic disease (p =
      0.143). Compared with the clear cell variety unclassified disease was associated
      with larger tumors (p = 0.005), increased risk of adrenal gland involvement (25%
      of cases, p = 0.0001), direct invasion to adjacent organs (42%, p = 0.00001),
      bone (52%, p = 0.022), regional (52%, p = 0.0042) and nonregional lymph node
      (41%, p = 0.03) metastases. Nephrectomy was less likely to be attempted or
      completed in unclassified renal cell carcinoma cases (61%, p = 0.00007).
      Unclassified histology was a significant indicator for poor prognosis on
      multivariate analysis (p <0.0001). Median survival in patients with unclassified
      renal cell carcinoma was 4.3 months. Nephrectomy alone did not confer any
      survival advantage in these cases (p = 0.1086), while immunotherapy did (p =
      0.008). The combination of nephrectomy and immunotherapy yielded improved
      survival over immunotherapy alone (p = 0.0356) but patients with unclassified
      renal cell carcinoma were significantly less likely than those with clear cell
      disease to be eligible for immunotherapy regimens (p = 0.05). CONCLUSIONS:
      Unclassified renal cell carcinoma is associated with distinct and highly
      aggressive biological behavior, and poor clinical outcome. Whenever feasible,
      immunotherapy with nephrectomy is warranted.

PMID- 12187198
TI  - Phase II trial of weekly intravenous gemcitabine administration with interferon
      and interleukin-2 immunotherapy for metastatic renal cell cancer.
AB  - PURPOSE: Since metastatic renal cell carcinoma has a poor prognosis and treatment
      strategies, including hormone therapy, chemotherapy and immunotherapy, have
      little impact on the quality of life and global survival statistics, new interest
      has recently focused on the combination of immuno-chemotherapy using pyrimidine
      analogues, such as gemcitabine. MATERIALS AND METHODS: In a phase II study 16
      patients with metastatic renal cell carcinoma were treated with 1,000 mg./m.
      gemcitabine intravenously on days 1, 8, 15 and 28 for 6 months, 3 MU (1 MU = 1 x
      10(6) IU) interferon (IFN)-alpha intramuscularly 3 times a week and 4.5 million
      IU interleukin (IL)-2 subcutaneously daily for 5 days a week for 2 consecutive
      weeks every month for 6 months. Responding and nonprogressing cases were
      maintained on immunotherapy consisting of IFN-alpha and IL-2 for further 6
      months. RESULTS: In 15 evaluable patients overall response rate (1 complete
      response plus 3 partial response) was 28% while stable disease was achieved in 7
      (47%). Median survival duration was 20 months (range, 9 to 26+) and median time
      to tumor progression was 14 months (6 to 26+). The complete response lasted 24+
      months and partial response lasted 16 months. The regimen was well tolerated with
      only 1 case of neutropenia (WHO grade 3), while anorexia, fatigue and flu-like
      symptoms were the most common toxicity problems but were never greater than grade
      2. CONCLUSIONS: Despite the small sample size, this study demonstrates that
      gemcitabine combined with standard doses of IFN-alpha and low doses of IL-2 is
      effective treatment for metastatic renal cell carcinoma. This biotherapy was well
      tolerated and resulted in an optimum objective response and relatively long-term
      survival.

PMID- 12187199
TI  - Doxorubicin and ifosfamide in patients with metastatic sarcomatoid renal cell
      carcinoma: a phase II study of the Genitourinary Group of the French Federation
      of Cancer Centers.
AB  - PURPOSE: We assessed the efficacy and toxicity of a chemotherapy regimen
      combining doxorubicin and ifosfamide in patients with metastatic sarcomatoid
      renal cell carcinoma. MATERIALS AND METHODS: Of the 25 patients included in a
      prospective multicenter phase II trial 23 were evaluable for efficacy and
      toxicity studies after pathological review. RESULTS: A median of 3 cycles per
      patient (range 1 to 8) was administered. No objective response was observed.
      Median time to progression was 2.2 months and median overall survival was 3.9
      months. A single patient died of toxicity. CONCLUSIONS: The results do not
      support the standard use of doxorubicin/ifosfamide chemotherapy in patients with
      metastatic sarcomatoid renal cell carcinoma.

PMID- 12187200
TI  - Renal cell carcinoma with tumor thrombus: is cytoreductive nephrectomy for
      advanced disease associated with an increased complication rate?
AB  - PURPOSE: We examined whether cytoreductive nephrectomy in patients with venous
      tumor thrombus and metastatic disease is associated with more complications than
      in those with thrombus without metastatic disease. MATERIALS AND METHODS: Between
      1989 and 2000, 74 patients with renal vein extension, 87 with inferior vena caval
      extension and 491 without tumor thrombus underwent nephrectomy at our
      institution. Metastatic and nonmetastatic renal vein extension in 51 and 23
      cases, inferior vena caval extension in 54 and 33, and nontumor thrombus in 171
      and 320, respectively, were compared for symptoms at presentation, surgical data,
      mortality and complications. RESULTS: For nonmetastatic and metastatic inferior
      vena caval extension presenting symptoms, hospital stay, surgical time and the
      number of patients undergoing thoraco-abdominal incision, lymph node dissection,
      venacavotomy alone for thrombus and adrenal sparing surgery were similar. Five
      patients with thrombus died intraoperatively or postoperatively, including 3.1%
      with and 0.8% without thrombus (p = 0.03), while 3 had metastatic (2.3%) and 2
      (2.6%) had nonmetastatic disease. The rate of postoperative complications was
      higher in thrombus cases overall but there was no difference in nonmetastatic and
      metastatic disease with thrombus. On multivariate analysis inferior vena caval
      thrombus (odds ratio 10.5), adjacent organ resection due to locally advanced
      tumor (odds ratio 6), partial nephrectomy (odds ratio 3.8), regional lymph node
      involvement (odds ratio 1.7) and lower preoperative hemoglobin (odds ratio 1.6)
      were independent variables predicting bleeding requiring transfusion. Inferior
      vena caval thrombus (odds ratio 1.7) and adjacent organ resection (odds ratio 2)
      were also associated with nonhemorrhagic complications. Systemic metastasis was
      not an independent risk factor in either analysis. CONCLUSIONS: To our knowledge
      there are no published data comparing surgical complications in patients with
      metastatic and nonmetastatic renal cell carcinoma who have gross tumor thrombus.
      Cytoreductive surgery in patients with thrombus and metastasis is not associated
      with an increase in the extent of surgery, morbidity or mortality compared with
      their counterparts with nonmetastatic disease.

PMID- 12187201
TI  - Interobserver discrepancy using the 1998 World Health Organization/International
      Society of Urologic Pathology classification of urothelial neoplasms: practical
      choices for patient care.
AB  - PURPOSE: Morphological classifications designed by experts to stratify neoplasms
      according to biological potential must define categories that are reproducible
      among practitioners or the schemes actually create the heterogeneous populations
      that they seek to avoid. The application of the 1998 World Health
      Organization/International Society of Urologic Pathology scheme for urothelial
      neoplasms was studied in a community practice setting. We documented interpretive
      discrepancies for each category of neoplasm and determined whether a period of
      pathologist education may have a positive effect on the frequency of discrepant
      interpretations. The results suggest that patients may benefit from modifying the
      classification system. MATERIALS AND METHODS: A consecutive series of specimens
      was divided into learning and study sets that were each independently examined by
      3 pathologists. Specimens in the learning set were interpreted without previous
      structured education, while those in the study set were interpreted immediately
      after intensive education. Interpretations for each specimen were compared and
      interpretive discrepancies were analyzed. RESULTS: Case distribution after
      education was similar among the pathologists but interpretations for any
      particular specimen often differed. The level of interpretive discrepancies
      varied according to the morphological similarity among categories in the
      classification scheme and was not necessarily decreased by education. When
      pathologists were required to discriminate between papillary urothelial neoplasm
      of low malignant potential and low grade carcinoma, the discrepancies were 50%
      after education compared with 39% before education. In contrast, there were no
      discrepancies when the discrimination was between papillary urothelial neoplasm
      of low malignant potential and high grade carcinoma or carcinoma in situ.
      Eliminating categories with poor reproducibility markedly improved the likelihood
      of unanimous agreement among practitioners but a probably irreducible level of
      10% discrepancies remained. CONCLUSIONS: The 1998 World Health
      Organization/International Society of Urologic Pathology classification of
      urothelial neoplasms requires certain discriminations that cannot be reliably
      made by practitioners. Modifying the scheme to create categories of low grade
      neoplasm and high grade carcinoma would markedly increase its practical value to
      patients without significantly altering patient care.

PMID- 12187202
TI  - DNA damage repair in bladder urothelium after the Chernobyl accident in Ukraine.
AB  - PURPOSE: We determined whether base and nucleotide excision repair is activated
      in bladder urothelium by chronic persistent low doses of ionizing radiation in
      male patients with benign prostate hyperplasia and females with chronic cystitis
      living more than 15 years in Cs contaminated areas after the Chernobyl accident
      in Ukraine. MATERIALS AND METHODS: Bladder urothelial biopsies from 204 patients
      were subjected to histological examination and biopsies from 35 were subjected to
      immunohistochemical study of 8-hydroxy-2'deoxyguanosine, 8-oxoguanine-DNA
      glycosylase, apurinic/apyrimidinic endonuclease and xeroderma pigmentosum A
      endonuclease. RESULTS: Chronic proliferative atypical cystitis with multiple foci
      of dysplasia and carcinoma in situ were observed in 139 (89%) and in 91 (58%) of
      156 group 1 patients from radio contaminated areas, respectively, as well as 10
      small transitional cell carcinomas. Chronic cystitis with areas of dysplasia was
      detected in 9 of 48 patients (19%) in control group 2 from clean (without radio
      contamination) areas of Ukraine. Greatly elevated levels of 8-hydroxy
      2'deoxyguanosine, 8-oxoguanine-DNA-glycosylase, apurinic/apyrimidinic
      endonuclease and xeroderma pigmentosum A were evident in the urothelium in group
      1, accompanied by increased Cs in the urine. CONCLUSIONS: These findings support
      the hypothesis that significant activation of DNA damage repair (base and
      nucleotide excision repair) is induced by the oxidative stress generated by long
      term low doses of ionizing radiation. The levels of DNA oxidative adducts
      pointing to mutagenic and carcinogenic potential were in line with the
      histopathologically diagnosed urothelial lesions.

PMID- 12187203
TI  - Correlation of cystoscopy with histology of recurrent papillary tumors of the
      bladder.
AB  - PURPOSE: We correlated individual urologist impressions of tumor stage and grade
      of recurrent papillary bladder tumors at cystoscopy with histological findings
      after transurethral resection to determine whether cystoscopy can reliably
      identify low grade, noninvasive papillary tumor for outpatient fulguration.
      MATERIALS AND METHODS: A total of 144 recurrent papillary bladder tumors
      identified on outpatient flexible cystoscopy were classified as low grade and
      noninvasive (stage Ta grade 1), high grade and noninvasive (stage Ta grade 3) or
      invasive (stage T1). Voided urine cytology was also performed. The cystoscopic
      impression of each tumor was correlated with the final histological findings of
      tumor stage and grade after transurethral resection. RESULTS: Cystoscopy
      classified 97 tumors as stage Ta grade 1 and 47 as stage Ta grade 3 or stage T1.
      Cystoscopy correctly predicted the tumor stage and grade of 93% of stage Ta grade
      1 and 99% of stage Ta grade 1 lesions associated with negative urine cytology.
      CONCLUSIONS: Urologists can usually identify noninvasive, low grade recurrent
      papillary tumors on followup cystoscopy that may be treated safely with
      outpatient fulguration.

PMID- 12187204
TI  - Perioperative single dose instillation of epirubicin or interferon-alpha after
      transurethral resection for the prophylaxis of primary superficial bladder cancer
      recurrence: a prospective randomized multicenter study--FinnBladder III long-term
      results.
AB  - PURPOSE: We evaluated the long-term efficacy of a single dose of interferon or
      epirubicin administered immediately after transurethral resection compared with
      transurethral resection alone for primary superficial bladder cancer recurrence.
      MATERIAL AND METHODS: A total of 200 patients with primary superficial stages Ta
      to T1, grades 1 to 3 bladder cancer were randomized into 3 treatment groups,
      including transurethral resection alone, transurethral resection plus 50
      milliunits interferon-alpha2b and transurethral resection plus 100 mg.
      epirubicin. The primary end point was time to first recurrence. RESULTS: At a
      median followup of 72 months we observed a sustained effect of a single
      epirubicin instillation compared with other treatments. To date only 46% of the
      patients in group 3 have experienced recurrence in contrast to 73% and 68% in
      groups 1 and 2, respectively (p = 0.002). At 72 months the Kaplan-Meier disease
      free estimates were 24%, 31% and 51% in groups 1 to 3, respectively (p = 0.002).
      The Cox multivariate model revealed a more than 2-fold relative risk of
      recurrence in group 1 versus group 3 (p <0.001). Other significant variables
      predicting recurrence were grade and the number of tumors. CONCLUSIONS: A single
      perioperative instillation of 100 mg. epirubicin causes a significant and
      sustained decrease in primary superficial bladder cancer recurrence, whereas a
      single dose of 50 milliunits interferon-alpha2b is ineffective for prophylaxis.

PMID- 12187205
TI  - Clinical value of prostate specific antigen based parameters for the detection of
      prostate cancer on repeat biopsy: the usefulness of complexed prostate specific
      antigen adjusted for transition zone volume.
AB  - PURPOSE: To our knowledge the indications for repeat prostate needle biopsy in
      men whose previous transrectal ultrasound guided biopsy results revealed no
      evidence of cancer have not yet been defined. We identified the most effective
      method for detecting prostate cancer on repeat biopsy. MATERIALS AND METHODS: One
      or more systematic repeat prostate biopsies were performed in 144 consecutive
      patients, including 86 with prostate specific antigen (PSA) levels between 4 and
      10 ng./ml. at repeat biopsy. Men in whom cancer was detected on repeat biopsies
      were compared with their counterparts in terms of digital rectal examination
      findings, PSA based parameters and an atypical prostate on initial prostate
      biopsy. RESULTS: Prostate cancer was detected on repeat biopsy in 39 of the 144
      patients and in 19 on subset analysis of 86. Serum PSA levels at repeat biopsy
      did not differ significantly in patients with and without prostate cancer.
      According to receiver operating characteristics analysis the alpha1
      antichymotrypsin-PSA complex adjusted for transition zone volume had the greatest
      area under the curve values, that is 0.756 for all 144 patients and 0.768 for the
      subset analysis of 86. Multiple logistic regression analysis of the subset of 86
      patients showed that alpha1-antichymotrypsin-PSA complex adjusted for transition
      zone volume was the only significant independent predictor of cancer.
      CONCLUSIONS: alpha1-Antichymotrypsin-PSA complex adjusted for transition zone
      volume was the most powerful predictor of cancer in men who had undergone
      previous negative prostate biopsies. This parameter may be used to avoid more
      unnecessary repeat biopsies with an acceptable decrease in sensitivity.

PMID- 12187206
TI  - A centralized comparison of radical perineal and retropubic prostatectomy
      specimens: is there a difference according to the surgical approach?
AB  - PURPOSE: We performed a central review of pathology specimens from radical
      perineal and radical retropubic prostatectomies performed by a single surgeon. We
      determined whether differences exist in the 2 approaches in regard to the ability
      to obtain adequate surgical margins around the tumor and adequate extracapsular
      tissue around the prostate, and avoid inadvertent capsular incision. MATERIALS
      AND METHODS: The review included whole mount prostates from 60 patients who
      underwent radical retropubic prostatectomy and 40 who underwent radical perineal
      prostatectomy. The pathologist (N. S. G.) was blinded to the surgical approach.
      All prostatectomies were consecutive and performed by the same surgeon (H. J.
      K.). To ensure consistency of the pathological measurements patients were
      excluded from analysis if they had undergone preoperative androgen ablation or a
      nerve sparing procedure, leaving 45 retropubic and 27 perineal prostatectomy
      specimens for further evaluation. Pertinent clinical parameters were assessed and
      a detailed pathological analysis of each specimen was performed. RESULTS: In the
      retropubic and perineal groups 78% of the tumors were organ confined (stage pT2)
      with extracapsular extension (stage pT3) in the majority of the remaining
      patients. There was no significant difference in the positive margin rate for the
      retropubic and perineal procedures (16% and 22%, p = 0.53) or for Gleason 6 and 7
      tumors only in the 2 groups (10% and 17%, respectively, p = 0.47). The capsular
      incision rate was 4% in each group. The distance of the tumor from the
      posterolateral margins and the amount of extracapsular tissue excised were
      equivalent in each group. Subgroups of patients with a prostate of less than 50
      gm. and containing only low grade, low stage neoplasms were also analyzed.
      Subgroup analysis showed no difference in any variable. CONCLUSIONS: Radical
      perineal prostatectomy is comparable to radical retropubic prostatectomy for
      obtaining adequate surgical margins, avoiding inadvertent capsular incisions and
      excising adequate extracapsular tissue around tumor foci. Additional patient
      accrual and prostate specific antigen followup would further help validate the
      similar efficacy of the 2 surgical approaches as treatment for prostate cancer.

PMID- 12187207
TI  - Prognostic significance of the nadir prostate specific antigen level after
      hormone therapy for prostate cancer.
AB  - PURPOSE: We determine whether the nadir prostate specific antigen (PSA) level
      after hormone therapy can be used to predict the progression to hormone
      refractory prostate cancer. MATERIALS AND METHODS: We reviewed the progressive
      status and survival of 177 patients with stage C or D prostate cancer who had
      received hormone therapy at our institution. The overall survival rate, incidence
      of progression to hormone refractory prostate cancer and interval until
      progression were analyzed with reference to the nadir PSA level. Multiple
      regression analysis was used to analyze the predictive factors for progression to
      hormone refractory prostate cancer, and the relative efficacy of the nadir PSA
      level in predicting progression was evaluated by receiver operating
      characteristics analysis. RESULTS: Median followup was 39 months (range 3 to 89)
      and 85.4% of patients (151) responded to treatment, of whom 77.5% (117) had
      progression to hormone refractory prostate cancer. Median time until nadir PSA
      levels were reached after hormone therapy was 8.1 months and median time until
      hormone refractory prostate cancer was 24.0 months. Nadir PSA levels were less
      than 0.2 ng./ml. in 31% of respondents, 0.2 to 1.0 ng./ml. in 23%, 1.1 to 10
      ng./ml. in 42% and greater than 10 ng./ml. in 5%. These groups had similar
      clinicopathological characteristics. Nadir PSA levels correlated significantly
      with pretreatment PSA levels, Gleason scores and progression to hormone
      refractory prostate cancer (p = 0.01, p <0.01 and p <0.001, respectively), and
      inversely correlated with the interval to the establishment of hormone refractory
      prostate cancer (r = -0.465, p <0.05). By univariate analysis bone metastasis,
      nadir PSA, PSA at 6 months after treatment and pretreatment PSA were
      significantly associated with progression to hormone refractory prostate cancer.
      Only the nadir PSA was calculated to be an independent factor by multivariate
      analysis. Receiver operating characteristics analysis indicated that nadir PSA
      predicted progression to hormone refractory prostate cancer after 2 years with an
      accuracy of 86.2%. With the lower limit of the nadir PSA level set to 1.1
      ng./ml., sensitivity was 80.3% and specificity was 83.8%, and these levels were
      deemed the most appropriate. Furthermore, nadir PSA after hormone therapy was an
      independent prognosticator for survival, as were initial levels of hemoglobin and
      alkaline phosphatase. CONCLUSIONS: The nadir PSA level after hormone therapy may
      be the most accurate factor predicting the progression to hormone refractory
      prostate cancer and is an independent prognostic factor for survival.
      Furthermore, a lower limit for the nadir PSA level of 1.1 ng./ml. gives optimal
      sensitivity and specificity.

PMID- 12187208
TI  - Serum testosterone suppression and potential for agonistic stimulation during
      chronic treatment with monthly and 3-month depot formulations of leuprolide
      acetate for advanced prostate cancer.
AB  - PURPOSE: The pattern of serum testosterone suppression as well as the potential
      for agonistic stimulation of serum testosterone during chronic treatment was
      compared in patients with prostate cancer randomized to receive 4 depot
      injections of either the monthly or 3-month depot formulations of leuprolide
      acetate in an open label study. MATERIALS AND METHODS: A total of 71 patients
      were enrolled in a randomized prospective study comparing the pattern of serum
      testosterone suppression and the potential for agonistic stimulation of serum
      testosterone following reinjection ("acute-on-chronic" effect) during treatment
      of advanced stage prostate cancer with monthly (7.5 mg.) and 3-month (22.5 mg.)
      depot formulations of leuprolide acetate. RESULTS: The 2 formulations produced
      nearly identical patterns of testosterone suppression which included uniform
      suppression throughout the duration of the dosing intervals. A transient minor
      "escape" from suppression (defined as a single testosterone value greater than 50
      ng./dl. once suppression was achieved) occurred in 1 patient receiving each
      formulation. Assessment of agonistic stimulation ("acute-on-chronic" response)
      following the second depot injection as well as the depot injection following 3
      months of treatment for each formulation revealed no pattern of stimulation.
      CONCLUSIONS: We conclude that monthly and 3-month sustained release (depot)
      formulations of leuprolide acetate provide consistent, uniform suppression of
      serum testosterone throughout the respective dosing intervals, and that the
      initial depot injection of each formulation provides sufficient pituitary
      desensitization to prevent agnostic stimulation of serum testosterone during
      chronic treatment.

PMID- 12187209
TI  - Skeletal fractures negatively correlate with overall survival in men with
      prostate cancer.
AB  - PURPOSE: We assessed the correlation of skeletal fracture with survival in men
      with prostate cancer on chronic androgen suppressive therapy. MATERIALS AND
      METHODS: A total of 195 consecutive patients on chronic androgen suppression for
      prostate cancer were evaluated for the history and type of skeletal fracture.
      Correlation with overall survival was performed via multivariate analysis.
      RESULTS: Of these 195 men 24 reported skeletal fracture since the diagnosis of
      prostate cancer. Median overall survival was 121 and 160 months in men without
      and with a history of skeletal fracture since the diagnosis of prostate cancer,
      respectively (p = 0.04). A history of skeletal fracture was retained as a
      negative predictor of survival on forward stepwise regression analysis (RR = 7.4,
      p = 0.007). CONCLUSIONS: Our results suggest that skeletal fracture in patients
      with prostate cancer is an independent and adverse predictor of survival.
      Consideration for screening men at greatest risk via bone mineral density
      measurements and initiating empirical skeletal therapies (bisphosphonates,
      estrogens and so forth) may be warranted. This recommendation awaits validation
      through prospective randomized trials.

PMID- 12187211
TI  - Refluxing ureterointestinal anastomosis for continent cutaneous urinary
      diversion.
AB  - PURPOSE: We question the statement that anti-refluxing ureteral implantation is
      mandatory in low pressure, high capacity reservoirs. In a series of patients with
      ureteral obstruction after implantation with an anti-refluxing submucosal tunnel
      reimplantation was performed as a direct ureter-pouch anastomosis. The same
      technique was used for primary anastomosis in a later group of patients as the
      method of choice for ileocolic and colonic continent urinary diversion. MATERIALS
      AND METHODS: Direct ureteral reimplantation was performed in 10 patients in whom
      a total of 19 obstructed renal units were associated with an ileocolic reservoir.
      The retroperitoneal supracostal approach was used to avoid complications caused
      by repeat laparotomy. The ileocecal reservoir was opened superior and the
      obstructed ureter was identified and reimplanted via a buttonhole. The same
      technique was used for primary anastomosis in 20 patients (40 renal units), in
      whom the ureter was implanted in an ileocecal (10) or colonic (10) pouch.
      RESULTS: Postoperatively complications did not develop in any patient.
      Radiography of the pouch postoperatively showed renal reflux in only 1 renal
      unit. In the group with reimplanted ureters median followup was 81 months (range
      10 to 120). Of the 19 obstructed ureters 14 returned to normal, while 5 showed
      persistent grade I dilatation. Median followup in patients with primary direct
      ureteral anastomosis was 20 months (range 2 to 36). Of the 22 preoperatively
      dilated systems 20 returned to normal and none of the 18 nondilated systems was
      obstructed. CONCLUSIONS: Direct ureter-pouch reimplantation proved to be simple
      and safe. When performed primarily for continent urinary diversion, the
      anastomosis was anti-refluxing in pouches with high capacity and low pressure.
      The advantage of this technique is the low risk of ureteral obstruction and
      subsequent deterioration in kidney function.

PMID- 12187210
TI  - Impact of previous local treatment for prostate cancer on subsequent metastatic
      disease.
AB  - PURPOSE: Metastatic prostate cancer, which is the precursor of most deaths from
      the disease, is treated most commonly with hormonal therapy. Generally the
      primary tumor is never treated. Due to evidence that controlling other primary
      neoplasms affects patient survival we examined the impact of radical
      prostatectomy and radiotherapy on the outcome in patients with metastatic
      prostate cancer in the context of a randomized clinical trial. MATERIALS AND
      METHODS: Southwest Oncology Group Study 8894 randomized 1,286 men with metastatic
      prostate cancer to orchiectomy and placebo or orchiectomy and flutamide. We
      performed proportional hazards analysis of variables previously identified to
      have a significant impact on survival. In this analysis we determined the impact
      of previous radical prostatectomy or radiotherapy on survival. RESULTS: Previous
      radical prostatectomy in patients with metastatic prostate cancer was associated
      with a statistically significant decrease in the risk of death (hazard ratio
      0.77, 95% confidence interval 0.53 to 0.89) relative to those who did not undergo
      earlier prostatectomy. Conversely previous radiotherapy was associated with a
      greater risk of death in those who had previously undergone prostatectomy and
      those who received no definitive earlier therapy. CONCLUSIONS: It must be
      stressed that this intriguing observation was a secondary analysis of a phase III
      study. Nevertheless, it raises the question of whether control of the primary
      tumor impacts the ultimate outcome in patients with advanced prostate cancer. The
      suggestion of the role of radical prostatectomy in locally advanced prostate
      cancer, the now established role of extirpative therapy for renal cell carcinoma
      and the suggestion of this phenomenon in ovarian carcinoma should prompt further
      evaluation of this finding in other data sets. It may provide new opportunities
      for clinical trials.

PMID- 12187212
TI  - Primary localized amyloidosis of the bladder: experience with dimethyl sulfoxide
      therapy.
AB  - PURPOSE: We present our long-term experience with intravesical dimethyl sulfoxide
      (DMSO) for primary localized amyloidosis of the bladder. MATERIALS AND METHODS:
      The study included 4 males and 2 females 28 to 68 years old (mean age 54) at
      diagnosis of biopsy proven primary localized amyloidosis involving the bladder
      diffusely or extensively in 1 locale. All patients had normal upper urinary
      tracts. They continued to be symptomatic (hematuria in 3, irritative voiding
      symptoms in 1, and hematuria and irritative voiding symptoms in 2) despite
      conventional transurethral destructive therapy. Every 2 weeks they received 30
      minute instillations of 50 ml. 50% DMSO intravesically for 3 months (patient 1),
      6 months (1) and 1 year (4). RESULTS: Therapy failed at 3 and 6 months in 2
      patients of whom 1 with a contracted bladder underwent cystectomy and another was
      stabilized for 1 year with laser therapy. In the remaining 4 patients who were
      followed for 6 years disease stabilized for 2 to 6 years (mean 3.5) but 3 later
      required additional therapy including repeat DMSO in 1 and laser therapy in 2.
      CONCLUSIONS: Diffuse or locally extensive bladder involvement by primary
      localized amyloidosis usually fails to respond to conventional transurethral
      destructive surgical procedures. Collectively, our experience and the literature
      suggest that intravesical DMSO can be a bladder saving measure and help resolve
      ureterovesical obstruction in some patients. High recurrence rate mandates
      lifelong cystoscopic surveillance.

PMID- 12187213
TI  - Single dose levofloxacin prophylaxis for prostate biopsy in patients at low risk.
AB  - PURPOSE: We determine if a single 500 mg. oral tablet of levofloxacin represents
      adequate prophylaxis for patients at low risk who undergo transrectal prostate
      biopsy. MATERIALS AND METHODS: From April 2000 to May 2001 we prospectively
      evaluated 400 consecutive men who underwent transrectal needle biopsy of the
      prostate after a single 500 mg. oral dose of levofloxacin. Under an institutional
      review board approved protocol the drug was issued under a standing order by a
      clinic nurse 30 to 60 minutes before the procedure. Patients were issued 2
      additional daily doses of levofloxacin if they were deemed at increased risk for
      infectious complications, that is if they had a large prostate more than 75 cc,
      diabetes mellitus, recent steroid use, severe voiding dysfunction or immune
      compromise. No patient received a cleansing enema before the procedure.
      Complications, the number of biopsy cores, prostate size and cancer detection
      rates were assessed. RESULTS: Only 1 of the 377 patients at low risk in whom
      biopsy was completed experienced a symptomatic urinary tract infection (0.27%).
      None of the 23 men at high risk who received additional doses of levofloxacin
      experienced a complication. Thus, the overall infection rate was 1 of 400 cases
      (0.25%) in this series. A mean of 7 biopsy cores (range 2 to 16) was obtained per
      patient and mean prostate volume was 49.75 cc (range 12 to 150). Prostate cancer
      was present in 93 patients (23%). CONCLUSIONS: A single 500 mg. dose of
      levofloxacin before transrectal needle biopsy of the prostate is effective and
      safe in patients at low risk. The administration of prophylaxis by a clinic nurse
      under a standing order optimizes patient compliance and physician efficiency. In
      patients at higher risk for infection additional antibiotic administration
      appears to provide adequate prophylaxis.

PMID- 12187214
TI  - Outpatient anterior urethroplasty: outcome analysis and patient selection
      criteria.
AB  - PURPOSE: We compared the outcomes of anterior urethroplasty for stricture disease
      performed on an outpatient and an inpatient basis. MATERIALS AND METHODS: We
      reviewed the records of 78, 1-stage anterior urethroplasties performed via
      excision with primary anastomosis, buccal mucosal graft or penile fasciocutaneous
      skin flap techniques from September 1997 to December 2000 by a single surgeon (A.
      F. M.). All patients had more than 1 year of followup (range 1 to 4.5). Of the
      graft procedures only those in the bulbar urethra were included in analysis.
      Outpatient procedures were defined as those in which the patient was discharged
      home within 24 hours. Clinical outcome was considered a failure when
      instrumentation was required postoperatively. RESULTS: Of the 78 anterior
      urethral repairs 54 (69%) were performed on an outpatient basis, including 50
      (93%) in which the outcome was successful compared with 88% (21) of the 24
      inpatient procedures. Excision with primary anastomosis had the highest
      outpatient rate (28 of 31 patients or 90%), followed by penile skin flaps (16 of
      25 or 64%) and buccal mucosal grafts (10 of 22 or 45%). Patient characteristics
      were significantly associated with outpatient procedures, including younger mean
      age (36 versus 46 years), shorter mean stricture length (3.1 versus 6.6 cm.) and
      shorter mean operative time (3.2 versus 4.66 hours) (p <0.05). CONCLUSIONS:
      Anterior urethral reconstruction can often be completed safely and effectively on
      an outpatient basis.

PMID- 12187215
TI  - Does gender or age affect the efficacy and safety of tolterodine?
AB  - PURPOSE: We compared the importance of patient age and gender relative to the
      intensity of baseline symptoms of overactive bladder in the therapeutic response
      to the muscarinic receptor antagonist tolterodine. MATERIALS AND METHODS: Data
      from an open label, observational study of 2,250 patients with overactive bladder
      treated for 12 weeks with tolterodine were analyzed for alterations in frequency,
      urgency and urge incontinence, and for global efficacy and tolerability using
      logistic regression analysis, stratifying for gender, age, baseline symptom
      intensity and tolterodine dose. RESULTS: Gender or tolterodine dose were not
      consistently associated with altered treatment efficacy. Greater age was
      associated with a slight but statistically significant decrease in treatment
      efficacy. Patients with great baseline symptom intensity had greater treatment
      associated improvement but a lesser chance to become symptom-free. Even with a
      large number of patients no statistically significant gender or age associated
      alterations in the tolerability of tolterodine treatment were detected.
      CONCLUSIONS: The extent of the therapeutic response to tolterodine is largely
      determined by the extent of baseline symptoms. While gender does not affect the
      efficacy or tolerability of tolterodine in a clinically relevant manner, advanced
      age is associated with a slight decrease in efficacy but not in tolerability.

PMID- 12187216
TI  - Urinary continence after radical retropubic prostatectomy: relationship with
      membranous urethral length on preoperative endorectal magnetic resonance imaging.
AB  - PURPOSE: We determined whether membranous urethral length on preoperative
      magnetic resonance imaging (MRI) is predictive of urinary continence after
      radical retropubic prostatectomy. MATERIALS AND METHODS: Membranous urethral
      length was measured on preoperative endorectal MRI in 211 consecutive patients
      with newly diagnosed prostate cancer before radical retropubic prostatectomy
      performed by a single surgeon. Neurovascular bundle resection was done in 60
      cases. After surgery the time to stable postoperative continence was recorded in
      180 cases and the level of stable continence was graded on a 5-point scale of 1
      complete continence to 5-complete incontinence. RESULTS: After controlling for
      age and surgical technique multivariate analysis showed that membranous urethral
      length was related to time to stable postoperative continence (p = 0.02), such
      that a longer membranous urethra was associated with a shorter time to stable
      continence. For example, 1 year after surgery 120 of the 134 patients (89%) with
      a preoperative membranous urethral length of greater than 12 mm. were completely
      continent compared with 35 of the 46 (77%) with a preoperative length of 12 mm.
      or less. CONCLUSIONS: On endorectal MRI before radical prostatectomy a longer
      membranous urethra is associated with significantly more rapid return of urinary
      continence after surgery.

PMID- 12187217
TI  - Magnetic stimulation of the sacral roots for the treatment of urinary frequency
      and urge incontinence: an investigational study and placebo controlled trial.
AB  - PURPOSE: We designed an investigational study and placebo controlled trial to
      evaluate the efficacy of magnetic stimulation of the sacral roots for treating
      urinary frequency and urge incontinence. MATERIALS AND METHODS: A total of 48
      women 43 to 75 years old (mean age 61) with the complaint of urinary frequency
      and/or urge incontinence were studied. We applied 15 Hz. repetitive magnetic
      stimulation of the sacral roots with 50% intensity output for 5 seconds per
      minute for 30 minutes. Urodynamic investigations during magnetic stimulation were
      performed in 11 cases to evaluate acute effects for lowering urinary tract
      function. Another 37 women were enrolled in a placebo controlled study to
      investigate short-term effects. The mean number of voids daily, mean urine volume
      per void, number of leaks for 3 days and quality of life score were evaluated
      before and 1 week after stimulation. RESULTS: Urodynamic investigations revealed
      apparent elevation in mean maximum urethral closure pressure plus or minus
      standard deviation during stimulation in all 11 cases (8.4 +/- 3.6 cm. water, p =
      0.00001) and a significant increase in mean bladder capacity after stimulation
      (58.2 +/- 50.2 ml., p = 0.003). In the placebo controlled study all parameters
      significantly improved in the active stimulation group. Intergroup comparison
      showed that mean urine volume per void, mean number of leaks and mean quality of
      life score improved more significantly in the active than in the sham stimulation
      group (23.5 +/- 25.6 ml. versus 6.2 +/- 22.5, p = 0.04, 3.6 +/- 4.1 versus 0.4 +/
      1.4, p = 0.04 and 1.4 +/- 1.3 versus 0.4 +/- 0.8, p = 0.01, respectively). No
      adverse effects were noted in any patients. CONCLUSIONS: These results suggest
      that magnetic stimulation of the sacral roots may be useful for treating urinary
      frequency and urge incontinence.

PMID- 12187218
TI  - Intact genetic material is present in commercially processed cadaver allografts
      used for pubovaginal slings.
AB  - PURPOSE: We determined the presence, quantitated the concentration and assessed
      the length of DNA present in 4 commercially available human cadaver allografts.
      MATERIALS AND METHODS: We evaluated 10 tissue samples from each of 4 commercial
      sources of human allograft (Mentor Corp., Santa Barbara, California;
      Musculoskeletal Transplant Foundation, Edison, New Jersey; Regeneration
      Technologies, Inc., Alachua, Florida; and Life Cell Corp., Woodlands, Texas) for
      intact DNA segments. All allograft samples underwent a standard extraction
      technique (proteinase K/sodium dodecyl sulfate/phenol) to isolate genetic
      material. Spectrophotometry evaluation was done to quantify DNA concentrations.
      Polymerase chain reaction was performed to amplify the retrieved DNA material.
      Agarose gel electrophoresis was performed to determine the size of DNA fragments.
      RESULTS: Of the 49 samples tested from all 4 commercial sources of human
      allograft fascia 39 (97.5%) contained DNA of 400 to 2,000 bp segments. A 400 bp
      DNA segment was present in 9 Mentor, 10 Musculoskeletal Transplant Foundation, 10
      Regeneration Technologies and 10 Life Cell samples. A 700 bp DNA segment was
      present in 10 Musculoskeletal Transplant Foundation, 10 Regeneration Technologies
      and 10 Life Cell allografts. A 2,000 bp DNA segment was present in 10 Life Cell
      tissues. CONCLUSIONS: Intact genetic material was present in all 4 commercially
      processed human allografts. Tissue processing did not completely eliminate intact
      DNA segments. The size of the intact DNA and the concentration of DNA varied
      widely based on tissue processing methods.

PMID- 12187219
TI  - Long-term results of Ingelman-Sundberg denervation procedure for urge
      incontinence refractory to medical therapy.
AB  - PURPOSE: Urge incontinence refractory to anticholinergic medication and
      behavioral techniques is a therapeutic challenge. We evaluated the durability of
      the modified Ingelman-Sundberg detrusor denervation procedure as minimally
      invasive surgical therapy for intractable urge incontinence. MATERIALS AND
      METHODS: Patients presenting with severe urge incontinence unresponsive to
      medical and/or behavioral therapy were injected subtrigonally with 10 ml. 0.25%
      bupivacaine. The patients were contacted 24 hours later to determine whether they
      experienced a decrease in urgency and urge incontinent episodes. The 28 patients
      with temporary resolution of symptoms were offered operative management. All
      patients were evaluated with history, physical examination and fluoroscopic
      urodynamics. The procedure consists of transvaginal dissection of the perivesical
      fascia from the area of the trigone, including sharp division of the terminal
      branches of the pelvic nerve. RESULTS: A total of 28 patients 28 to 83 years old
      (mean age 54.6) underwent the Ingelman-Sundberg procedure from April 1993 to
      September 1997. All patients presented with a history of urge incontinence, 10
      reported concomitant stress incontinence and 10 had documented unstable detrusor
      contractions on urodynamic evaluation. Needle suspension and the pubovaginal
      sling procedure were performed with the Ingelman-Sundberg procedure in 1 case
      each. Mean followup was 44.1 months (range 14 to 67). Of the patients 15 (54%)
      achieved the complete durable resolution of urge incontinence, 4 (14%) were
      improved and 9 (32%) were unchanged. CONCLUSIONS: Ingelman-Sundberg bladder
      denervation resulted in a 68% long-term cure or improved rate in a difficult
      patient population, namely those with intractable urge incontinence. This brief,
      minimally invasive procedure is an excellent alternative to more aggressive
      surgical options.

PMID- 12187220
TI  - Leukocyte and bacterial counts do not correlate with severity of symptoms in men
      with chronic prostatitis: the National Institutes of Health Chronic Prostatitis
      Cohort Study.
AB  - PURPOSE: We examine whether leukocytes and bacteria correlate with symptom
      severity in men with chronic prostatitis/chronic pelvic pain syndrome. MATERIALS
      AND METHODS: All 488 men screened into the National Institutes of Health Chronic
      Prostatitis Cohort Study before close of recruitment on August 22, 2001 were
      selected for analysis. The National Institutes of Health Chronic Prostatitis
      Symptom Index, including subscores, were used to measure symptoms. Urethral
      inflammation was defined as white blood cell (WBC) counts of 1 or more (1+) in
      the first voided urine. Participants were classified as category IIIa based on
      WBC counts of 5 or more, or 10 or more (5+, 10+) in the expressed prostatic
      secretion, or 1+ or 5+ either in the post-expressed prostatic secretion urine
      (voided urine 3) or semen. Uropathogens were classified as localizing if the
      designated bacterial species were absent in voided urine 1 and voided urine 2 but
      present in expressed prostatic secretion, voided urine 3 or semen, or present in
      expressed prostatic secretion, voided urine 3 or semen at 2 log concentrations
      higher than at voided urine 1 or 2. Associations between symptoms, and
      inflammation and infection were investigated using generalized Mantel-Haenszel
      methods. RESULTS: Of all participants 50% had urethral leukocytes and of 397 with
      expressed prostatic secretion samples 194 (49%) and 122 (31%) had 5+ or 10+ WBCs
      in expressed prostatic secretion, respectively. The prevalence of category IIIa
      ranged from 90% to 54%, depending on the composite set of cut points. None of the
      index measures were statistically different (p >0.10) for selected leukocytosis
      subgroups. Based on prostate and semen cultures, 37 of 488 men (8%) had at least
      1 localizing uropathogen. None of the index measures were statistically different
      (p >0.10) for selected bacterial culture subgroups. CONCLUSIONS: Although men
      with chronic prostatitis routinely receive anti-inflammatory and antimicrobial
      therapy, we found that leukocytes and bacterial counts as we defined them do not
      correlate with severity of symptoms. These findings suggest that factors other
      than leukocytes and bacteria also contribute to symptoms associated with chronic
      pelvic pain syndrome.

PMID- 12187221
TI  - Intravesical potassium sensitivity in patients with prostatitis.
AB  - PURPOSE: Prostatitis and interstitial cystitis encompass similar symptoms and may
      be manifestations of a single pathophysiological process in the lower urinary
      tract. Most patients with interstitial cystitis have urinary epithelial
      dysfunction, as indicated by a positive intravesical potassium sensitivity test.
      We used the potassium sensitivity test for the presence of epithelial dysfunction
      in men with diagnosed prostatitis. MATERIALS AND METHODS: We administered the
      potassium sensitivity test in men who presented with the signs and symptoms of
      prostatitis (urgency/frequency and/or pelvic pain) after being diagnosed with
      prostatitis and receiving at least 1 course of antibiotic treatment administered
      by a urologist other than one of us. We also surveyed the patients for urinary
      symptoms and pain locations using 2 self-evaluation questionnaires. RESULTS: A
      total of 44 patients with prostatitis completed the questionnaires and underwent
      the potassium sensitivity test. Of the 44 men 37 (84%) had positive potassium
      sensitivity test results, 89% reported urinary urgency/frequency and 82% reported
      pain. Pain locations included the perineum, lower abdomen, lower back, penis,
      testes, scrotum and rectum as well as dysuria and post-void pain. Pain with
      sexual intercourse was reported by 75% of the patients with prostatitis.
      CONCLUSIONS: The rate of positive potassium sensitivity test results in patients
      with prostatitis is almost identical to that reported in those with interstitial
      cystitis (84% and 79%, respectively), suggesting that prostatitis and
      interstitial cystitis may be a continuum of lower urinary epithelial dysfunction.
      Similar to patients with interstitial cystitis, most patients with prostatitis
      experience pain during sexual intercourse and perceive pain at locations
      throughout the pelvis. We suggest reclassifying the prostatitis-interstitial
      cystitis disease process as lower urinary dysfunctional epithelium.

PMID- 12187222
TI  - A randomized controlled trial comparing transurethral resection of the prostate,
      contact laser prostatectomy and electrovaporization in men with benign prostatic
      hyperplasia: urodynamic effects.
AB  - PURPOSE: We compared urodynamic and uroflowmetry improvements in men with lower
      urinary tract symptoms suggestive of benign prostatic hyperplasia (BPH) after
      transurethral prostate resection, contact laser prostatectomy and
      electrovaporization. MATERIALS AND METHODS: A prospective randomized controlled
      trial was performed in men with lower urinary tract symptoms suggestive of BPH
      who met the criteria of the International Scientific Committee on BPH, had a
      prostate volume of between 20 and 65 ml., and a Schafer obstruction grade of 2 or
      greater. Before and 6 months after treatment urodynamics and free uroflowmetry
      were performed. RESULTS: A total of 50, 45 and 46 men were randomized to
      transurethral prostate resection, laser treatment and electrovaporization,
      respectively. Baseline characteristics were similar in the 3 groups. Detrusor
      contractility did not change in any of the treatment groups. The average maximum
      free flow rate increased by a factor of 2.4 after transurethral prostate
      resection, 2.5 after laser prostatectomy and 2.4 after electrovaporization. The
      Schafer obstruction grade decreased by a factor of 0.3 in all groups. Obstruction
      (Schafer grade greater than 2) was not noted after transurethral prostate
      resection or electrovaporization but it was evident in 2 patients after laser
      prostatectomy. Effective capacity increased by a factor of 1.5 or more. The
      incidence of detrusor instability was decreased by half in all groups. The
      incidence of significant post-void residual urine volume decreased in all groups.
      CONCLUSIONS: There were no significant differences in the improvement in
      urodynamic and uroflowmetry parameters 6 months after treatment when comparing
      transurethral prostate resection, contact laser prostatectomy and
      electrovaporization in men with lower urinary tract symptoms suggestive of BPH.

PMID- 12187223
TI  - Conventional versus microdissection testicular sperm extraction for
      nonobstructive azoospermia.
AB  - PURPOSE: We established a practical and safe strategy for testicular sperm
      extraction (TESE) in patients with nonobstructive azoospermia and compared
      conventional with microdissection TESE. MATERIALS AND METHODS: In a retrospective
      comparative study 46 patients, including 22 with obstructive and 24 with
      nonobstructive azoospermia, underwent conventional TESE. Another 100 patients,
      including 26 with obstructive and 74 with nonobstructive azoospermia, underwent
      microdissection TESE. Conventional TESE was performed via 3 small 5 mm. incisions
      in the tunica albuginea. Microdissection TESE was performed by making a 3 to 4
      cm. incision in the tunica albuginea under operating microscopy, avoiding the
      underlying testicular artery. Seminiferous tubules that appeared dilated and
      opaque were harvested. Sperm recovery rates were compared, as were complication
      rates assessed by ultrasonographic and endocrinological evaluations. RESULTS: In
      obstructive azoospermia cases the sperm recovery rate was 100% for each
      procedure. In nonobstructive azoospermia cases sperm were recovered in 16.7% and
      44.6% by conventional and microdissection TESE, respectively (p = 0.0271). In
      cases of histologically diagnosed maturation arrest the sperm recovery rate was
      37.5% and 75%, respectively (p = 0.22585). In cases of the Sertoli-cell-only
      syndrome the sperm recovery rate was 6.3% and 33.9%, respectively (p = 0.0494).
      We identified dilated and opaque seminiferous tubules containing spermatozoa
      under operating microscopy in 22.2% of patients with maturation arrest and in
      63.2% with the Sertoli-cell-only syndrome. The complication rate was
      significantly lower for microdissection than for conventional TESE. CONCLUSIONS:
      In nonobstructive cases, especially those of the Sertoli-cell-only syndrome,
      microdissection TESE can effectively retrieve spermatozoa and minimize the risk
      of complications.

PMID- 12187224
TI  - Men with nonobstructive azoospermia have Leydig cell hypertrophy but not
      hyperplasia.
AB  - PURPOSE: We determined whether testicular histology in men with spermatogenic
      failure due to nonobstructive azoospermia shows true Leydig cell hyperplasia.
      MATERIALS AND METHODS: Testicular biopsy specimens from 17 patients evaluated for
      infertility were retrospectively analyzed. Interstitial, tubular and Leydig cell
      volume were quantitatively evaluated. The total volume and number of Leydig cells
      per testicle were then calculated. RESULTS: In 10 patients with obstructive
      azoospermia testicular histology showed normal spermatogenic function, while 7
      had nonobstructive azoospermia. Average testicular volume plus or minus standard
      deviation was significantly larger in those with obstructive versus
      nonobstructive azoospermia (18.0 +/- 7.0 versus 9.3 +/- 8.7 cc, p = 0.025).
      Interstitial versus tubular volume was 32% of the total testis in the obstructive
      and 63% in the nonobstructive groups (p = 0.003). Although Leydig cell volume was
      proportionally greater in men with nonobstructive versus obstructive azoospermia
      (13.3% versus 0.05%, p = 0.045), there was no significant difference in the
      average number of Leydig cells per testicle (3.96 x 10 and 6.17 x 10,
      respectively, p = 0.16). The average volume of individual Leydig cells was
      significantly greater in men with the nonobstructive condition (253.0 +/- 98.7
      versus 174.0 +/- 57.7 microm., p = 0.045). CONCLUSIONS: These results suggest
      that men with nonobstructive azoospermia and those with normal spermatogenesis
      have an equivalent number of Leydig cells. However, the Leydig cells are
      hypertrophic and occupy a larger proportion of total testis volume in men with
      nonobstructive azoospermia. Therefore, patients with spermatogenic failure show
      Leydig cell hypertrophy but not hyperplasia.

PMID- 12187225
TI  - The effects of subinguinal varicocelectomy on Kruger morphology and semen
      parameters.
AB  - PURPOSE: We studied the effect of varicocele ligation on Kruger strict morphology
      criteria and semen parameters in patients with infertility. MATERIALS AND
      METHODS: A total of 90 patients diagnosed with varicoceles and a normal
      morphological sperm ratio of less than 14% were evaluated before and 6 months
      after varicocelectomy. Preoperatively and postoperatively sperm density, motility
      and morphology using Kruger strict criteria were analyzed. The Wilcoxon test was
      used to measure levels of statistical significance in all analyses. RESULTS:
      Significant improvement in sperm concentration and motility was evident after
      varicocele ligation (p <0.0002 and <0.0001, respectively). Using the Kruger
      classification sperm morphology evaluation revealed a significant increase in the
      percent of normal forms, and of forms with head and acrosome defects (p <0.0001,
      <0.0014 and <0.0028, respectively). There were no concomitant changes in strict
      morphology in forms with mid piece and tail defects or immature forms (p >0.05).
      Of the 90 patients 18 (20%) achieved a successful full-term pregnancy, including
      14 via natural cycle intercourse and 4 by intrauterine insemination. CONCLUSIONS:
      Surgical correction of varicocele was associated with significant improvement in
      density, motility and sperm morphology evaluated using the Kruger classification.

PMID- 12187226
TI  - A retrospective review of 307 men with Peyronie's disease.
AB  - PURPOSE: We discuss the clinical appearance and natural outcome of Peyronie's
      disease. MATERIALS AND METHODS: During an 8-year period 307 men with Peyronie's
      disease were evaluated, and clinical characteristics, risk (factors), penile
      deformities, erectile status and outcome were analyzed. RESULTS: Mean patient age
      plus or minus standard deviation was 52.8 +/- 9.3 years (range 23 to 76). Penile
      deformity, pain on erection and palpable nodule were the most common (85%)
      presenting symptoms, usually in different combinations. The remaining 15% of men
      (mean age 59.4 +/- 6.5 years) were not aware of the penile deformity and were
      diagnosed during standard evaluation for erectile dysfunction. Dorsal (45.6%) and
      lateral (29.3%) were the most common curvatures. The degree of deformity was less
      than 30 degrees in 42.7% of patients, 31 to 60 degrees in 38.8% and greater than
      60 degrees in 18.6%. At least 1 risk factor for systemic vascular disease was
      identified in 67.5% of patients, and hypercholesterolemia and diabetes were the
      most common. Patients with at least 1 risk factor had a significantly higher risk
      for severe penile deformity. Of the men 54.4% complained of erectile dysfunction
      and the probability of diminished erectile capacity was 86.7% in patients older
      than 60 years, with Peyronie's disease for more than 12 months and at least 1
      risk factor. Of 63 patients presenting with the acute phase of disease penile
      deformity deteriorated in 30.2%, did not change in 66.7% and resolved
      spontaneously in 3.2% without any treatment after a mean followup of 8.4 months.
      CONCLUSIONS: Our data show that penile deformities are disabling (greater than 30
      degrees) in 62.5% of cases. Risk factors, such as serum lipid abnormalities,
      diabetes and hypertension, seem to have significant impact on the severity of
      symptoms and outcome. Patients must be informed that Peyronie's disease is
      progressive in 30.2% without treatment and spontaneous resolution is rare.

PMID- 12187227
TI  - Minimally invasive laparoscopic neobladder.
AB  - PURPOSE: To our knowledge orthotopic reconstruction after laparoscopic radical
      cystectomy has not been described in the human. After anatomical and surgical
      studies on cadavers we developed an original technique and performed the first
      laparoscopic radical cystectomy with pelvic lymphadenectomy and ileal orthotopic
      neobladder reconstruction in a patient. MATERIALS AND METHODS: Our technique has
      3 steps, namely laparoscopic pelvic clearance, external reconstruction and
      laparoscopic reconstruction. After cystoprostatectomy and lymphadenectomy were
      completed via laparoscopy we removed the surgical specimens through a 5 cm.
      supraumbilical incision. Through the same incision an ileal loop was extracted
      from the abdominal cavity, isolated, detubularized and partially reconfigured.
      Intestinal continuity was restored extracorporeally. All intestinal loops were
      inserted back into the abdomen and pneumoperitoneum was started again. The
      ureteroileal (nipple valve) and urethroileal anastomoses were formed via
      laparoscopy and the neobladder was then completed with an intracorporeal running
      suture. RESULTS: Operative time was 450 minutes and blood loss was 350 ml.
      Postoperatively pain was minimal. The patient was ambulatory, regained bowel
      activity on postoperative day 2 and began food intake 2 days later. He was
      discharged home on postoperative day 7 with an indwelling catheter, which was
      removed after 7 days. Histopathological examination showed organ confined bladder
      cancer without margin invasion. CONCLUSIONS: To our knowledge we report the first
      case of laparoscopic radical cystectomy with ileal orthotopic reconstruction.
      This original technique combines the advantages of minimally invasive laparoscopy
      with the speed and safety of open surgery.

PMID- 12187228
TI  - Ultrasound guided needle localization and microsurgical exploration for
      incidental nonpalpable testicular tumors.
AB  - PURPOSE: We describe a technique by which incidental, nonpalpable intratesticular
      tumors are excised using intraoperative ultrasonography and the operating
      microscope. MATERIALS AND METHODS: Men with impalpable intratesticular tumors
      incidentally detected by ultrasonography underwent intraoperative ultrasound
      guided needle localization and microsurgical exploration of the mass. The testis
      was delivered through an inguinal incision and placed on ice to minimize warm
      ischemia. Two rubber shod vascular clamps were placed across the spermatic cord.
      The tumor was identified by ultrasound and localized with a 30 gauge needle,
      which was placed adjacent to the tumor. An operating microscope providing 6x to
      25x magnification was used to excise the lesion with a 2 to 5 mm. margin. Tissue
      diagnosis was obtained by frozen section. Multiple random biopsies of the
      remaining parenchyma were done to confirm absent malignancy. RESULTS: Ultrasound
      showed incidental, nonpalpable testis tumors in 4 of the 65 men who underwent
      infertility evaluation and were entered into the microsurgical testis biopsy
      database between January 1995 and December 2001. All lesions were hypoechoic.
      Frozen section analysis of the lesions revealed 2 Leydig cell tumors, 1 mass with
      an inconclusive pathological diagnosis and 1 inflammatory mass. On permanent
      section the latter 2 lesions were seminoma. The seminomas were 1.6 and 0.9 cm. in
      the greatest diameter, and the Leydig cell tumors were 0.35 and 0.2 cm.,
      respectively. Random biopsies were positive for seminoma and intratubular germ
      cell neoplasia in both testes with seminoma. These 2 patients subsequently opted
      to undergo radical orchiectomy. No residual tumor was detected in either radical
      orchiectomy specimen. CONCLUSIONS: Intraoperative ultrasound guided needle
      localization with microsurgical exploration is a safe and effective approach to
      even small impalpable testicular masses. This technique provides the opportunity
      to identify and remove benign and malignant lesions, and preserve the testis when
      the lesion is benign. In cases of a solitary testis or bilateral synchronous
      lesions the technique allows a potentially testis sparing operation for small
      malignancies.

PMID- 12187229
TI  - Endoluminal ureteroileal anastomosis.
AB  - PURPOSE: We present an alternative technique used to complete the ureteroileal
      anastomosis during the formation of an ileal conduit or neobladder. MATERIALS AND
      METHODS: Using an intraoperative camera to produce digital images and with the
      aid of computer graphics a visual and descriptive method was used to illustrate
      the technique. It involves eversion of the proximal ileal segment with
      exteriorization of the ileal mucosa. RESULTS: This technique allows for direct
      visualization of the mucosa-to-mucosa ureteroileal anastomosis. With normal
      tissues it does not require ureteral stents postoperatively. We have been
      performing this technique for the last 20 years and have never observed
      symptomatic urinary leakage. CONCLUSIONS: We present an alternative technique for
      completing the ureteroileal anastomosis with direct visualization and minimal
      morbidity.

PMID- 12187230
TI  - Planned hand assisted laparoscopic left radical nephrectomy involving a level 1
      renal vein tumor thrombus.

PMID- 12187231
TI  - Primary synovial sarcoma of the kidney diagnosed by molecular detection of SYT
      SSX fusion transcripts.

PMID- 12187232
TI  - Skin abscess after intravesical instillation of bacillus Calmette-Guerin for
      prophylactic treatment of transitional cell carcinoma.

PMID- 12187233
TI  - Verrucous carcinoma of the penis treated with cryosurgery.

PMID- 12187234
TI  - Unilateral autonomous testicular testosterone production mimicking androgen
      independent prostate cancer.

PMID- 12187235
TI  - Solitary fibrous tumor of the prostate.

PMID- 12187236
TI  - The hemophagocytic syndrome in prostate cancer revealed by disseminated
      carcinomatosis of the bone marrow.

PMID- 12187237
TI  - Prostate brachytherapy seed migration to a coronary artery found during
      angiography.

PMID- 12187238
TI  - Chemotherapy induced complete remission in malignant phyllodes tumor of the
      prostate metastasizing to the lung.

PMID- 12187240
TI  - Use of transurethral needle ablation of the prostate for acute urinary retention.

PMID- 12187239
TI  - Acute urinary retention associated with the use of cyclooxygenase-2 inhibitors.

PMID- 12187241
TI  - Re: the prevalence of testicular microlithiasis in an asymptomatic population of
      men 18 to 35 years old.

PMID- 12187242
TI  - Re: laparoscopic radical nephrectomy: cancer control for renal cell carcinoma.

PMID- 12187243
TI  - Re: vaginal extraction of the intact specimen following laparoscopic radical
      nephrectomy.

PMID- 12187244
TI  - Re: long-term followup after laparoscopic radical nephrectomy.

PMID- 12187245
TI  - Re: organ sparing surgery for malignant germ cell tumor of the testis.

PMID- 12187246
TI  - Re: editorial comment: quality control of radical prostatectomy: a feasibility
      study.

PMID- 12187247
TI  - Reliability of contrast enhanced sonography with harmonic imaging for detecting
      early renal scarring in experimental pyelonephritis in a porcine model:
      preliminary results.
AB  - PURPOSE: Contrast medium enhanced harmonic ultrasound is a recently developed
      ultrasound technique that improves the assessment of renal parenchymal
      vascularity. We performed a preliminary study to define the ability of contrast
      enhanced ultrasound with harmonic imaging to detect and localize renal scars in a
      porcine model of experimentally induced pyelonephritis. MATERIALS AND METHODS:
      Vesicoureteral reflux was surgically induced in 10 pigs weighing 10 kg. with the
      contralateral kidney serving as a control. Approximately 4 weeks after the
      creation of vesicoureteral reflux cystography confirmed reflux. Infection was
      induced by placing a suspension of paraffin broth impregnated with Escherichia
      coli in the bladder of each pig. At 4 to 8 weeks (mean 6.5) after the induction
      of infection a radiologist blinded to the side of the previous procedure
      performed conventional gray scale ultrasound, color Doppler ultrasound and
      contrast enhanced ultrasound with harmonic power imaging. The animals were
      sacrificed; the kidneys were inspected and tissues from the upper, mid and lower
      poles were sent for culture and histological examination. Histology results were
      compared with the findings of the 3 ultrasound modalities. RESULTS: All 10 pigs
      survived the surgical procedures with no complications. Post-contrast harmonic
      ultrasound images were available in 9 pigs (18 renal units). Harmonic ultrasound
      revealed decreased blood flow in 11 renal units, including the upper pole in 7,
      lower pole in 3, and upper and lower poles in 2. Renal tissue cultures were
      positive in 11 renal units (6 refluxing units). Histological findings revealed
      fibrosis in 10 renal units (8 refluxing units). Harmonic ultrasound findings in
      these 10 renal units showed 9 with changes consistent with inflammation or scars.
      Using histological results as the gold standard for renal injury harmonic
      ultrasound was more sensitive than gray scale ultrasound for detecting renal
      injury with 90% sensitivity, 75% specificity, 81% positive predictive value and
      85% negative predictive value. CONCLUSIONS: Preliminary results indicate that
      contrast enhanced ultrasound with harmonic imaging is a sensitive method for
      determining renal scarring without the need for radiation exposure. It may be
      prove to be a useful adjunct for evaluating children who present with urinary
      tract infection.

PMID- 12187248
TI  - Long-term followup of prenatally detected severe bilateral newborn hydronephrosis
      initially managed nonoperatively.
AB  - PURPOSE: We determine the outcome of severe bilateral primary ureteropelvic
      junction type hydronephrosis detected prenatally and managed postnatally with an
      initially nonoperative protocol. MATERIALS AND METHODS: A total of 19 newborns
      (38 kidneys) with prenatally diagnosed primary grade 3 to 4 bilateral
      hydronephrosis were followed nonoperatively for a mean of 54 months (range 14 to
      187). If urinary obstruction with evidence of renal deterioration (decreased
      differential function and/or progressive hydronephrosis) occurred pyeloplasty was
      performed. RESULTS: Pyeloplasty was required in 13 kidneys (35%) in 9 patients
      (bilateral 4, unilateral 5). Age at pyeloplasty ranged from 2 to 22 months (mean
      6.5) in 12 patients and 64 months in 1. The remaining 25 kidneys were followed
      nonoperatively (bilateral 20, unilateral 5). At last followup the Society for
      Fetal Urology grade of hydronephrosis in kidneys followed nonoperatively was 0 to
      2 in 21 and 3 in 4, compared to 0 to 2 in 9 and Society for Fetal Urology 3 in 4
      kidneys treated with pyeloplasty. Mean followup required for the most severely
      hydronephrotic kidney to achieve maximum ultrasound improvement was 10 months
      (range 3 to 34) for kidneys followed nonoperatively and 14 months (4-31) for
      kidneys after pyeloplasty. Differential renal function was measured in each
      kidney pair and compared using the difference in percent function between the 2
      kidneys. In the nonoperative group mean initial difference in percent function
      was 8% (range 6% to 20%) and mean final difference was 5% (2% to 8%). In the
      pyeloplasty group mean initial difference in percent function was 16% (range 8%
      to 30%) and mean final difference was 7% (2% to 16%). With close followup and
      prompt pyeloplasty renal function improved to greater than pre-deterioration
      levels in all kidneys. CONCLUSIONS: These data represent the natural history of
      severe bilateral newborn hydronephrosis. Renal dilatation and function improve
      with time in most kidneys. Close followup is required in the first 2 years of
      life to identify the subgroup (35%) of children with obstruction that requires
      prompt surgery. Such an approach prevented permanent loss of renal function.
      Nonoperative management with close followup during the first 2 years appears to
      be a safe and recommended approach for neonates with primary bilateral
      ureteropelvic junction type hydronephrosis.

PMID- 12187249
TI  - Editorial: The long-term followup of prenatally detected severe bilateral newborn
      hydronephrosis initially managed nonoperatively.

PMID- 12187250
TI  - Histology of upper pole is unaffected by prenatal diagnosis in duplex system
      ureteroceles.
AB  - PURPOSE: We determined whether the histology of upper pole nephrectomy specimens
      vary with prenatal detection or ureterocele position. MATERIALS AND METHODS:
      Between 1992 and 2000, 95 patients with ureteroceles associated with a duplex
      system underwent surgical interventions, including upper pole nephrectomy in 60.
      A total of 55 specimens, of which 25 and 30 involved a prenatal and postnatal
      diagnosis, and 18 and 37 involved an intravesical and extravesical location,
      respectively, were available for independent review by a single pathologist.
      Histological lesions were classified into the 5 categories of chronic
      interstitial inflammation, fibrosis, tubular atrophy, glomerulosclerosis and
      dysplasia. Each category was divided into moderate/severe histological lesions
      (greater than 25% involvement) and minimal/mild lesions (25% or less
      involvement). RESULTS: A moderate/severe histological lesion was identified in 38
      patients (69%) and a minimal/mild lesion was detected in 17 (31%), while
      dysplasia was present in 35 (64%). There was no significant difference in
      histological lesions and mode of presentation. In contrast to intravesical
      ureteroceles, extravesical ureteroceles were associated with severe fibrosis and
      tubular atrophy (p <0.05). Chronic interstitial inflammation, fibrosis, tubular
      atrophy and glomerulosclerosis in each specimen were graded moderate/severe
      (greater than 25% involved) in 55%, 67%, 66% and 53%, respectively. CONCLUSIONS:
      Prenatally diagnosed ureteroceles were not associated with less severe upper pole
      histological lesions. We noted pathological differences when comparing specimens
      according to ureterocele position, but chronic inflammation and dysplasia were
      similar in intravesical and extravesical ureterocele cases. It appears that the
      histological lesions observed are not progressive or reversible. Therefore, the
      goals of clinical management should focus on providing adequate drainage,
      antibiotic prophylaxis coverage and followup of reflux rather than the
      preservation or enhancement of upper pole function.

PMID- 12187252
TI  - Renal cell carcinoma in a 2-year-old child with tuberous sclerosis.

PMID- 12187251
TI  - Stented versus nonstented pediatric pyeloplasty: a modern series and review of
      the literature.
AB  - PURPOSE: Dismembered pyeloplasty remains the principal surgical therapy for
      pediatric ureteropelvic junction obstruction, although the method of
      postoperative drainage continues to be debated. We compared stented versus
      nonstented repairs in a modern series. MATERIALS AND METHODS: We evaluated 117
      pediatric dismembered pyeloplasties performed by 3 pediatric urologists at 2
      institutions from 1991 to 2000. Hospital stay, success rate and complication rate
      were reviewed. Results were compared with 833 evaluable cases in the literature.
      RESULTS: Of the 52 stented repairs urological complications developed in 6 (12%),
      including symptomatic urinary tract infection in 3 and temporary obstruction in
      3. Of the 65 nonstented repairs urological complications developed in 10 (15%),
      including prolonged leakage in 3, urinoma in 3, obstruction in 3 and urinary
      tract infection in 1. Mean hospitalization plus or minus standard error was
      shorter in the stented group (2.1 +/- 0.89 versus 2.6 +/- 1.1 days, p <0.02). We
      identified 9 previous studies comparing a total of 339 stented with 494
      nonstented repairs. Overall the number of complications was almost equal (12%
      versus 14%) but the stented group had more infections, whereas more leaks
      occurred in the nonstented group. The nonstented group required more secondary
      procedures (12 of 339 versus 45 of 494, p = 0.003). Hospital stay was 12 days for
      stented and 5 days for nonstented repair in these earlier series. CONCLUSIONS: In
      children the outcome of stented pyeloplasty is similar to that of nonstented
      repair. In contrast to previous reports, using a stent for drainage should not
      necessitate a longer hospital stay.

PMID- 12187253
TI  - Recurrent transitional cell carcinoma in a child with the Costello syndrome.

PMID- 12187254
TI  - Extravesical diverticuloplasty for repair of a paraureteral diverticulum and the
      associated refluxing ureter.
AB  - PURPOSE: Extravesical diverticuloplasty for repairing a paraureteral (Hutch)
      diverticulum and the related refluxing ureter is presented. MATERIALS AND
      METHODS: Of the 16 children in this study 10 had bilateral paraureteral
      diverticula with associated bilateral vesicoureteral reflux, 2 had bilateral
      paraureteral diverticula with a bilateral duplicated ureter, unilateral duplex
      refluxing ureters and contralateral lower moiety vesicoureteral reflux, and 4 had
      a unilateral paraureteral diverticulum with an ipsilateral refluxing ureter. The
      anatomical relationship of the ureteral orifice and diverticulum was identified
      by cystourethroscopy preoperatively and confirmed during the extravesical
      operation. The surgical technique differed depending on the size of the
      diverticulum and the position of the ureteral opening when the bladder was
      completely distended. The larger prolapsed diverticular mucosa served as a
      backing for the detrusor muscle, which was closed over the ureter, and the
      smaller diverticulum was repaired as a dilated ureter. Overall 30 renal units
      with grades II to IV vesicoureteral reflux were corrected by this method.
      RESULTS: All patients were followed with ultrasound and voiding
      cystourethrography 3 and 9 months postoperatively. The diverticula with
      associated refluxing ureters were successfully cured. Neither postoperative
      recurrence nor ureteral obstruction were noted. CONCLUSIONS: Extravesical
      diverticuloplasty can be performed for many sizes of paraureteral diverticula and
      concomitantly for the associated refluxing ureter, including refluxing duplex
      ureters.

PMID- 12187255
TI  - Angiotensin II type 2 receptor gene is not responsible for familial
      vesicoureteral reflux.
AB  - PURPOSE: The renin-angiotensin system has an important role in the development of
      the kidney and ureter. It has been reported that disruption of the angiotensin II
      type 2 receptor (AT2) gene leads to congenital anomalies of the kidney and ureter
      in mice, including vesicoureteral reflux. In humans a single base A to G
      transition at position -1332 in intron 1 (A-1332G) of the AT2 gene has been
      reported to occur significantly more often in patients with ureteropelvic
      junction obstruction and primary obstructive megaureter than in controls. We
      investigate the incidence of A-1332G transition in patients with primary familial
      vesicoureteral reflux to determine if AT2 gene is involved in pathogenesis of
      this disease. MATERIALS AND METHODS: We evaluated the incidence of A-1332G
      transition in 82 male and 110 female patients, 111 male and 124 female
      nonaffected family members from 88 families in which 2 or more members had
      primary vesicoureteral reflux, and 106 male and 107 female controls with no
      unselected for reflux status. Genomic DNA was extracted from whole blood samples.
      Polymerase chain reaction method modified for fluorescent detection was used to
      type all samples for the A-1332G variant. Furthermore, to identify mutations in
      the coding sequence of the AT2 gene, we selected 61 patients from different
      families as well as 15 controls with no vesicoureteral reflux status. RESULTS:
      The incidence of A-1332G transition in male patients with primary familial
      vesicoureteral reflux and controls was 33% (27 of 82 patients) and 38% (41 of 106
      controls), respectively, and, the incidence of A-1332G substituted allele in
      female patients and controls was 47% (104 of 220 total alleles) and 50% (107 of
      214 total alleles), respectively. Moreover, the transmission/disequilibrium test
      revealed no significant skewing of genotype transmission from mother to children.
      None of the 61 patients or 15 controls carried by mutations or polymorphisms in
      the coding sequence of the AT2 gene. CONCLUSIONS: Although the AT2 gene has been
      reported to have a role in developmental anomalies of the kidney and ureter, our
      data indicate that it is not involved in the pathogenesis of primary familial
      vesicoureteral reflux.

PMID- 12187256
TI  - Prevalence of nocturnal enuresis and associated familial factors in primary
      school children in taiwan.
AB  - PURPOSE: We investigated the prevalence and associated factors of nocturnal
      enuresis in children in elementary schools in Taiwan. MATERIALS AND METHODS: A
      cross-sectional study of nocturnal enuresis in Taiwanese school children was
      performed in 10 primary schools in Tao-Yuan County, Taiwan. Questionnaires on
      demographic data, familial and physical conditions were completed by 7,225
      children assisted by their parents. RESULTS: The overall prevalence of nocturnal
      enuresis in Taiwanese primary school children was 5.5%. Decreasing age, male
      gender, family size, birth rank, parental education level and parental raising
      style were possible familial risk factors for nocturnal enuresis in this study.
      CONCLUSIONS: The study indicates a prevalence of nocturnal enuresis in the
      Taiwanese population comparable to that in western populations, showing that
      nocturnal enuresis is an international problem that should be considered
      seriously. Findings of familial factors associated with nocturnal enuresis
      provide a clue for future studies of psychosocial factors in different cultural
      societies and their intervention.

PMID- 12187257
TI  - Effect of spinal cord abnormalities on the function of the lower urinary tract in
      patients with anorectal abnormalities.
AB  - PURPOSE: We evaluated the effect of spinal cord abnormalities on lower urinary
      tract function in patients with anorectal abnormalities. MATERIALS AND METHODS:
      We examined 30 patients with anorectal anomalies mainly because of fecal or
      urinary incontinence. All patients underwent spinal magnetic resonance imaging
      and urodynamic investigation. RESULTS: Major lumbosacral abnormalities were
      detected in 57% of patients, including 13, 4 and 3 with a tethered cord,
      syringomyelia and caudal regression, respectively. Significant dysfunction of the
      lower urinary tract in 57% of the cases involved an overactive detrusor in 11,
      detrusor-sphincter dyssynergia in 4, distended bladder in 4 and lazy bladder in
      1. When the spinal cord was normal, 54% of the patients had abnormal urodynamic
      findings but when the spinal cord was abnormal, 59% had abnormal urodynamics.
      When the bony spine was normal, 33% of the patients had an abnormal spinal cord
      but when the bony spine was abnormal, 69% had an abnormal spinal cord.
      CONCLUSIONS: Patients with anorectal abnormalities and fecal or urinary
      incontinence problems often have an abnormal spinal cord and abnormal urodynamic
      findings. However, the state of the spinal cord is not the only factor explaining
      lower urinary tract function. Thus, the possibility of lower urinary tract
      dysfunction should be considered in each patient with anorectal abnormalities. If
      the patient has symptoms or findings suggesting abnormal lower urinary tract
      function urodynamic evaluation should be performed.

PMID- 12187258
TI  - Management of intrinsic sphincter deficiency in adolescent females with normal
      bladder emptying function.
AB  - PURPOSE: Intrinsic sphincter deficiency is rare in adolescent females with normal
      bladder emptying function. Information regarding the long-term outcome of therapy
      in this group of patients is sparse. We report our long-term experience with 3
      adolescent females with intrinsic sphincter deficiency and normal bladder
      function who were treated with an artificial urinary sphincter. We critically
      reviewed the literature regarding experience with anti-incontinence surgery in
      adolescent females, not only regarding the outcome of the surgical technique, but
      also issues not usually considered in older adults, including the impact of
      physical development and future childbearing. MATERIALS AND METHODS: The charts
      of 3 adolescent females with intrinsic sphincter deficiency were reviewed. In
      addition, relevant peer reviewed articles were selected by a MEDLINE search. The
      results of the artificial urinary sphincter, pubovaginal sling and periurethral
      injection of bulking agents were reviewed. Long-term efficacy, the complication
      rate, impact of pregnancy and physical development were assessed. RESULTS: The 3
      patients had an excellent long-term outcome with the artificial urinary
      sphincter, including 1 with 2 pregnancies that ended in a normal vaginal
      delivery. The literature showed that a good long-term outcome was consistently
      achieved with the artificial urinary sphincter. An equally good outcome was
      achieved with the pubovaginal sling but long-term data are lacking. While
      periurethral injection of a bulking agent provides good initial results, they do
      not appear to be durable. In addition, the artificial urinary sphincter does not
      appear to impact pregnancy or physical development negatively. CONCLUSION: Data
      support the artificial urinary sphincter and pubovaginal sling as effective
      therapies in adolescent females with intrinsic sphincter deficiency. However,
      long-term data on the pubovaginal sling are not available. When considering the
      impact on future childbearing and physical development, the artificial urinary
      sphincter is a favorable option.

PMID- 12187259
TI  - Congenital mid ureteral stricture presenting as prenatal hydronephrosis.

PMID- 12187260
TI  - Congenital urethral stricture.

PMID- 12187261
TI  - Diagnosis of urethral obstruction with prenatal magnetic resonance imaging.

PMID- 12187262
TI  - Approaches to modeling stromal-epithelial interactions.
AB  - PURPOSE Techniques that can be used to examine the molecular mechanisms of
      stromal-epithelial interactions are described. MATERIALS AND METHODS A historical
      perspective of available techniques is provided. Recent developments and examples
      are used to illustrate and provide descriptive literature references for these
      methods. Since the possibilities for manipulating experimental systems are
      enormous and rapidly expanding, the reader should be aware that this review is an
      overview of how data have been and could be obtained rather than a comprehensive
      listing of what has been achieved. This review focuses on studies performed in
      the organs of the urogenital tract to illustrate techniques that are
      available.RESULTS Recent technological innovations have impacted our ability to
      manipulate specific components and pathways of stromal-epithelial interactions.
      They include rapid developments in transgenic and gene knockout mouse technology,
      and the development of highly efficacious gene delivery and expression systems.
      CONCLUSIONS These technologies have the potential to transform our understanding
      of the mechanistic basis of intercellular communication and point the way toward
      new therapeutic approaches for benign and malignant proliferative conditions.

PMID- 12187263
TI  - Expression of osteopontin in rat kidneys: induction during ethylene glycol
      induced calcium oxalate nephrolithiasis.
AB  - PURPOSE: Osteopontin is a well-known component of stone matrix and a strong
      inhibitor of the nucleation, growth and aggregation of calcium oxalate crystals
      in vitro. To understand its involvement in vivo in calcium oxalate
      nephrolithiasis we investigated the renal expression and urinary excretion of
      osteopontin in normal rats, and rats with hyperoxaluria and calcium oxalate
      crystal deposits in the kidneys. MATERIALS AND METHODS: Calcium oxalate
      nephrolithiasis was induced by administering ethylene glycol.
      Immunohistochemistry and in situ hybridization were done to localize osteopontin
      and osteopontin messenger RNA in the kidneys, while sensitive reverse
      transcriptase quantitative competitive template polymerase chain reaction was
      performed to detect and quantify osteopontin messenger RNA expression. Urinary
      excretion was determined by sodium dodecyl sulfate-polyacrylamide gel
      electrophoresis and Western blot analysis, and then quantified by densitometry of
      the Western blots. RESULTS: Osteopontin expression in the kidneys was
      significantly increased after hyperoxaluria and it increased further after the
      deposition of calcium oxalate crystals in the kidneys. Urinary excretion of
      osteopontin increased concomitantly. The results reveal differences in renal
      responses after exposure to oxalate and calcium oxalate crystals. In normal
      kidneys osteopontin expression was limited to a small number of cells of the thin
      limbs of the loop of Henle and papillary surface epithelium. During hyperoxaluria
      osteopontin expression in the kidneys was increased but still mostly limited to
      cells of the thin limb and papillary surface epithelium. However, after calcium
      oxalate crystal deposition osteopontin expression was observed throughout the
      kidneys, including segments of the proximal tubules. CONCLUSIONS: In response to
      exposure to oxalate and calcium oxalate crystals renal epithelial cells increase
      the production of osteopontin, which may have a significant role in calcium
      oxalate nephrolithiasis.

PMID- 12187264
TI  - Adenovirus mediated gelsolin gene therapy for orthotopic human bladder cancer in
      nude mice.
AB  - PURPOSE: Gelsolin is an actin regulatory protein that is undetectable or reduced
      in human bladder tumors compared with normal epithelial cells. Whether the over
      expression of gelsolin could inhibit tumor growth was investigated in an
      orthotopic bladder cancer nude mouse model using recombinant adenovirus encoding
      wild-type gelsolin (Ad-GSN). MATERIALS AND METHODS: The 2 human bladder cancer
      cell lines KU-7 and UMUC-2 were transduced with Ad-GSN in vitro. Flow cytometric
      analysis was done to examine the cell cycle after transducing the adenovirus.
      Cell growth was compared with control groups of these cells transduced with
      adenovirus containing the Escherichia coli beta-galactosidase gene Ad-betagal. In
      vivo KU-7 cells were introduced into the bladder of nude mice (day 0), followed
      by 3 injections into the urethra (days 2 to 4) with Ad-GSN or Ad-betagal (1 x 10
      pfu). At 8 days after initial adenovirus exposure (day 10) each bladder was
      sectioned and stained, and the mass of the tumor was digitally determined.
      RESULTS: Bladder cancer cell growth (KU-7 and UMUC-2) was inhibited after these
      cells were transduced with Ad-GSN in vitro. Based on flow cytometric analysis
      over expression of gelsolin may cause these cells to arrest or delay at the G2/M
      phase of the cell cycle. In the orthotopic bladder cancer model the mass of the
      tumor was approximately 90% less in Ad-GSN treated animals than in controls.
      CONCLUSIONS: Ad-GSN provides a significant tumor suppressive effect on human
      bladder cancer cells in this orthotopic nude mouse model. Adenovirus mediated
      over expression of gelsolin may be useful therapy for human bladder cancer.

PMID- 12187265
TI  - No association of serum gonadal or pituitary hormones with prognostic parameters
      in stages T1 to T3 PN0M0 prostate cancer.
AB  - PURPOSE: Recent reports suggest a possible association of the clinical
      aggressiveness of prostate cancer with low serum testosterone, and high serum
      levels of lutenizing hormone (LH) and/or follicle-stimulating hormone (FSH). This
      hypothesis was tested in the current study. MATERIALS AND METHODS: Serum levels
      of testosterone, LH, FSH, estradiol and sex hormone-binding globulin were
      determined as well as the calculated ratio of testosterone-to-sex hormonebinding
      globulin in 370 patients with newly diagnosed, stages T1 to T3 pN0M0 prostate
      cancer. The results were related to T category, Gleason score and serum prostate
      specific antigen (PSA). RESULTS: No statistically significant association was
      found for the serum levels of testosterone, LH, FSH, estradiol, sex hormone
      binding globulin or the testosterone-to-sex hormone-binding globulin ratio with T
      category, Gleason score or PSA. In contrast to expectations, serum testosterone
      values within the lowest quartile were not associated with elevated LH. Of the
      370 patients 17 (5%) had serum testosterone below the normal range (8 nmol./l. or
      less) and only 3 of these 17 showed elevated LH levels. CONCLUSIONS: Serum levels
      reflecting the pituitary-gonadal axis at diagnosis are not associated with
      clinically used measures of tumor aggressiveness (T category, Gleason score or
      PSA) in patients with newly diagnosed T1 to T3 pN0M0 prostate cancer.

PMID- 12187266
TI  - CL1-SR39: A noninvasive molecular imaging model of prostate cancer suicide gene
      therapy using positron emission tomography.
AB  - PURPOSE: We developed a prostate cancer tumor model capable of being
      noninvasively imaged using positron emission tomography (PET) based on expression
      of the herpes simplex virus thymidine kinase (HSV1-tk) reporter gene. MATERIALS
      AND METHODS: The androgen independent, metastatic prostate cancer cell lines CL1
      and CL1-GFP were stably transfected with the mutant HSV1-tk gene pcDNA3.1/pCMV
      sr39tk, which has increased ability to phosphorylate penciclovir. The presence of
      the sr39tk gene product was analyzed by Western blot analysis and relative
      thymidine kinase enzyme activity was assessed by a functional thymidine kinase
      enzyme activity assay. Subcutaneous and orthotopic CL1 and CL1-SR39 tumor
      xenografts were established in SCID mice. The ability to image CL1-SR39 was
      assessed using fluorodeoxyglucose and F-penciclovir ( F-FHBG) micro-PET (a rodent
      PET scanner). To investigate the systemic distribution of intratumoral sr39tk
      injections established CL1 tumors were transiently injected with first generation
      adenoviral vectors carrying the sr39tk gene under control of the strong
      cytomegalovirus promoter Ad-CMV-HSV1-sr39tk and imaged using micro-PET. RESULTS:
      Transfection of sr39tk into CL1 cells was successful. CL1-SR39 thymidine kinase
      enzyme activity was greater than twice the activity of the glioma cell line C6
      SR39 control and above the threshold necessary for micro-PET detection.
      Fluorodeoxyglucose micro-PET in SCID mice was positive for CL1 and CL1-SR39
      tumors. Selective micro-PET of subcutaneous CL1-SR39 tumors was done using F
      FHBG. Micro-PET imaging after systemic and intratumoral injection of Ad-CMV-HSV1
      sr39tk revealed significant systemic transgene leakage with significant hepatic
      expression of sr39TK protein. CONCLUSIONS: Molecular based imaging of sr39tk
      transfected prostate cancer tumors and adenoviral delivered HSV1-tk suicide gene
      therapy based on the selective conversion and intracellular trapping of F-FHBG by
      sr39tk is feasible. Potential applications include noninvasive monitoring of the
      location, duration and intensity of gene constructs, which may contribute to the
      safety of clinical gene therapy protocols, and noninvasive imaging of the
      prostate cancer xenograft response to experimental therapy.

PMID- 12187267
TI  - A clinical study of 22.5 mg. La-2550: A new subcutaneous depot delivery system
      for leuprolide acetate for the treatment of prostate cancer.
AB  - PURPOSE: The safety, efficacy and pharmacokinetics of a unique 3-month
      subcutaneous depot of leuprolide acetate were investigated in patients with
      prostate cancer. MATERIALS AND METHODS: This open label, noncomparative, 6-month
      multicenter study enrolled 117 patients diagnosed with adenocarcinoma of the
      prostate. LA-2550 (22.5 mg. depot) (Atrix Laboratories, Fort Collins, Colorado)
      was administered subcutaneously once every 3 months. The primary efficacy
      parameter was serum testosterone 50 ng./dl. or less. Pharmacokinetics were
      analyzed in a subset of 22 patients. RESULTS: Of the 117 enrolled patients 111
      (98%) completed the 6-month study. Five patients withdrew for nontreatment
      related events and 1 was withdrawn because he received less than a full dose of
      the study drug. By day 28, 98% of patients had serum testosterone 50 ng./dl. or
      less and 84% had achieved 20 ng./dl. or less. By day 35 all patients had 50
      ng./dl. or less testosterone. A patient with a breakthrough response after
      testosterone suppression on day 49 (112 ng./dl.) regained suppression (27
      ng./dl.) 14 days after the second injection (day 98). At study completion all
      patients had 50 ng./dl. or less testosterone (mean plus or minus standard error
      of mean 10.1 +/- 0.07) and 104 of the 111 (94%) had 20 ng./dl. or less. From
      baseline to month 6 mean luteinizing hormone decreased from 9.2 +/- 1.1 to 0.08
      +/- 0.01 mIU/ml. and mean prostate specific antigen decreased more than 98%. No
      flare reactions were observed and patient assessments of bone pain and urinary
      symptoms were unchanged. The most common treatment related adverse event was hot
      flashes, which were mild in 57% of cases, moderate in 12% and severe in 0%.
      CONCLUSIONS: LA-2550 (22.5 mg. depot) produced and maintained safe and effective
      suppression of serum testosterone to well below the medical castrate level of 50
      ng./dl. or less.

PMID- 12187268
TI  - Neuroendocrine expression in node positive prostate cancer: correlation with
      systemic progression and patient survival.
AB  - PURPOSE: Neuroendocrine cells are ubiquitous but uncommon in benign and
      neoplastic prostate epithelium, and they are considered important for regulating
      cell growth and differentiation. The predictive value of neuroendocrine
      immunoreactivity for patient outcome after radical prostatectomy is uncertain. In
      this study we determined the expression of 2 important neuroendocrine markers,
      chromogranin and serotonin, in benign epithelium, primary prostate cancer and
      lymph node metastases, and correlated cellular expression with patient outcome.
      MATERIALS AND METHODS: We studied 196 patients with node positive prostate
      adenocarcinoma who underwent bilateral pelvic lymphadenectomy and radical
      prostatectomy at Mayo Clinic between 1987 and 1992. Mean followup was 6.8 years
      (range 0.3 to 11). The cellular expression of chromogranin and serotonin in
      matched samples of benign tissue, primary prostate cancer and lymph node
      metastases from the same patients was evaluated by immunohistochemical staining
      using commercially available monoclonal antibodies. Results were correlated with
      patient age, pathological findings (Gleason score, DNA ploidy and cancer volume)
      and patient outcome, including clinical progression, cancer specific and all
      cause survival. RESULTS: Chromogranin immunoreactivity was greater in benign
      prostatic epithelium and primary cancer cases (99% each) than in those of lymph
      node metastases (37.5%) (pairwise comparisons with metastases p <0.001). The mean
      incidence of immunoreactive cells in benign epithelium, primary cancer and
      metastases was 6% (median 5%), 6% (median 3%) and 2.2% (median 0%), respectively.
      Serotonin immunoreactivity was greatest in benign prostate epithelium cases
      (98.5%) with less in primary cancer (95%) and lymph node metastases (21.5%)
      (pairwise comparisons p <0.001). The mean incidence of immunoreactive cells in
      benign epithelium, primary cancer and metastases was 2.2% (median 3%), 2.4%
      (median 2%) and 0.4% (median 0%), respectively. Chromogranin expression was
      invariably greater than that of serotonin for all 3 diagnostic categories (p
      <0.0001). There was a marginally significant positive trend in the level of
      chromogranin expression in benign prostatic epithelium and systemic progression
      (p = 0.05) but no significant association with cancer specific or all cause
      survival (p >0.1). No significant association was observed of chromogranin
      expression in primary cancer or lymph node metastases with any patient outcomes
      (p >0.1). There was a significant association of the level of serotonin
      expression in benign prostatic epithelium with cancer specific survival (p =
      0.03) but no significant association with systemic progression or all cause
      survival (p > 0.1). There were positive trends in the association of serotonin
      immunoreactivity in primary cancer with systemic progression (p = 0.09) and
      cancer specific survival (p = 0.05) but not with all cause survival (p >0.1). No
      significant association was observed of serotonin expression in lymph node
      metastases with any patient outcomes (p >0.1). CONCLUSIONS: Benign prostatic
      epithelium and primary prostate cancer express a significantly greater number of
      chromogranin and serotonin immunoreactive cells than lymph node metastases,
      suggesting that decreased expression of neuroendocrine markers is involved in
      cancer progression. However, neuroendocrine expression was marginally useful for
      predicting the outcome in patients with node positive prostate cancer treated
      with radical prostatectomy.

PMID- 12187269
TI  - Receptor gene messenger RNA expression in metastatic lesions of prostate cancer.
AB  - PURPOSE: There are hardly any options for treating hormone refractory prostate
      cancer. Some groups have already suggested antitumor therapy of prostate cancer
      using agonists, antagonists or other concepts acting on luteinizing hormone
      releasing hormone (LH-RH) receptor. Few studies have been published to date on
      the detection of LH-RH receptors in human prostate cancer tissue. However, at
      this point it is completely unclear in this context whether metastasizing
      prostate cancer lesions, which may be major potential targets of a type of
      therapy, have any LH-RH receptors. In this study we examined tumor samples of
      lymph nodes from patients with prostate cancer obtained during radical
      prostatectomy and laparoscopic lymphadenectomy for the expression of LH-RH
      receptor messenger (m)RNA. MATERIALS AND METHODS: Multiplex reverse transcriptase
      polymerase chain reaction (RT-PCR) was done to detect the expression of the mRNA
      of LH-RH receptor, prostate specific antigen and beta-actin in pelvic lymph nodes
      from 100 patients with prostate cancer. RESULTS: In 27 patients at least 1
      histopathological metastasis (19) and/or positive RT-PCR for prostate specific
      antigen (22) was identified. In 7 of these patients (25.9%) RT-PCR revealed LH-RH
      mRNA expression. CONCLUSIONS: To our knowledge our study shows for the first time
      a rather low incidence of LH-RH receptor mRNA in primary pelvic lymph node
      metastases. However, since other studies show that an increased incidence of LH
      RH receptors is typical of the hormone refractory stage of the disease, further
      studies in this specific patient population may help explain the clinical
      importance of LH-RH receptors in the development of new therapeutic approaches to
      advanced prostate cancer.

PMID- 12187270
TI  - Small intestinal submucosa as a tunica albuginea graft material.
AB  - PURPOSE: We evaluated the morphological, immunological and functional response to
      small intestinal submucosa grafting of the tunica albuginea to determine its
      potential as a grafting material for penile surgery. MATERIALS AND METHODS: Male
      New Zealand White rabbits underwent a sham procedure (6) or tunical excision and
      grafting with small intestinal submucosa (6). The erectile response to the
      intracavernous vasoactive agents sodium nitroprusside plus a papaverine,
      phentolamine and prostaglandin E1 combination (Sigma Chemical Co., St. Louis,
      Missouri) was evaluated 45-day postoperatively. The area under the graft was
      evaluated for stromal collagen and smooth muscle content by Masson's trichrome
      stain. Protein expression of smooth muscle specific alpha-actin and the
      inflammatory markers inducible nitric oxide synthase (NOS) and transforming
      growth factor-beta1 (TGF-beta1) was evaluated by immunohistochemical methods.
      Total RNA was extracted from the corpora cavernosum underlying the small
      intestinal submucosa graft and reverse transcriptase-polymerase chain reaction
      (RT-PCR) was done using an Access system (Promega, Madison, Wisconsin) with gene
      specific primers for inducible NOS, TGF-beta1 and vascular endothelial growth
      factor (VEGF). RESULTS: Grafting of the tunica albuginea with small intestinal
      submucosa had no significant effect on the magnitude or duration of the erectile
      response to intracavernous vasoactive agents. Histological examination
      demonstrated no inflammatory changes in the tunica albuginea or corporeal tissue
      underlying the area of the small intestinal submucosa graft and there was no
      appreciable alteration in smooth muscle or collagen content. The 2 groups showed
      intense positive immunostaining to alpha-actin. Weak expression of TGF-beta1
      predominantly associated with smooth muscle fibers was identified in the 2 groups
      of rabbits by immunostaining and RT-PCR. No significant inducible NOS was
      detected by immunostaining or RT-PCR in either group. Strong VEGF expression was
      observed in grafted rabbits. The most noticeable (3-fold) increase in expression
      was detected in splice variant 165. CONCLUSIONS: Small intestinal submucosa
      grafting of the tunica albuginea preserves the duration and magnitude of the
      erectile response to vasoactive agents. This type of tunical grafting does not
      stimulate a significant inflammatory response, or cause corporeal fibrosis or
      loss of cavernous smooth muscle content. Stimulating VEGF may facilitate wound
      healing and the maintenance of normal erectile function.

PMID- 12187271
TI  - The role of endothelin-1 in ischemia-reperfusion induced acute inflammation of
      the bladder in rats.
AB  - PURPOSE: Endothelin (ET)-1 is causatively involved in ischemia-reperfusion
      induced acute inflammatory reactions and microcirculatory disturbances in many
      organs. We investigated the role of endothelin-1 in the microcirculatory
      consequences of ischemia-reperfusion of the bladder using intravital fluorescence
      videomicroscopy. MATERIALS AND METHODS: Male Sprague-Dawley rats were used in the
      experiments. The animals were randomly assigned to a sham operated group or to 1
      of 2 ischemia-reperfusion groups that underwent 60 minutes of ischemia followed
      by 30 minutes of bladder reperfusion. In 1 ischemia-reperfusion group the animals
      were pretreated with BQ 610, a specific ET-A receptor blocker. The bladder was
      placed on an especially designed stage for intravital fluorescence
      videomicroscopy measurements. Venular red blood cell velocity, functional
      capillary density, venular and arteriolar diameter, venular and arteriolar
      macromolecular leakage, and leukocyte-endothelial cell interactions in
      postcapillary venules were determined using a computer assisted analyzing system.
      RESULTS: Functional capillary density, red blood cell velocity, venular and
      arteriolar diameter were significantly decreased and macromolecular leakage was
      significantly enhanced after bladder ischemia-reperfusion. The number of rolling
      and adherent leukocytes was significantly increased in postcapillary venules.
      Pretreatment with BQ 610 was effective for attenuating the effects of ischemia
      reperfusion induced inflammation but could not completely prevent
      microcirculatory failure. CONCLUSIONS: Ischemia-reperfusion induced cystitis
      leads to significant impairment of the microcirculation and ET-1 is suggested to
      have an important role in this process. Pretreatment with an ET-A receptor
      antagonist reduces ischemia-reperfusion related microvascular disturbances in the
      bladder.

PMID- 12187272
TI  - Cyclooxygenase-2 expression is up-regulated in obstructed human ureter.
AB  - PURPOSE: Prostanoids produce significant effects on ureteral function and are
      synthesized by cyclooxygenase (COX) enzymes. COX is found in the 2 isoforms COX-1
      (a constitutive form) and COX-2 (an inducible form). Due to the side effects
      associated with COX-1 inhibition there is great interest in selective COX-2
      inhibition. We determined if COX-2 messenger (m)RNA and protein expression are
      regulated during ureteral obstruction. MATERIALS AND METHODS: mRNA analysis was
      performed using excess ureteral segments from 6 patients undergoing
      reconstructive procedures for chronic ureteral obstruction and 8 (normal ureter)
      undergoing donor nephrectomy after providing informed consent. All ureteral
      segments were snap frozen in liquid nitrogen and stored at -70C. RNA was isolated
      from the segments using phenol extraction and complementary DNA was synthesized
      by reverse transcription with murine leukemia virus reverse transcriptase
      (Promega Corp., Madison, Wisconsin). Semiquantitative reverse transcriptase
      polymerase chain reaction was performed using specific COX-2 gene primers with
      ribosomal S26 primers serving as the housekeeping gene. The polymerase chain
      reaction product was quantified by agarose gel electrophoresis and phospho
      imaging. The ratio of COX-2-to-S26 mRNA was compared. Additional segments were
      homogenized and total protein was extracted, separated via sodium dodecyl sulfate
      polyacrylamide gel electrophoresis and transferred to nitrocellulose membranes.
      These membranes were Western blotted for COX-2 and glyceraldehyde-3-phosphate
      dehydrogenase (housekeeping protein) with specific primary and secondary
      antibodies. RESULTS: The mean ratio of COX-2-to-S26 mRNA plus or minus standard
      error at 20, 22 and 24 cycles of amplification was 0.22 +/- 0.04 in the 8 normal
      ureters compared with 1.01 +/- 0.21 in the 6 obstructed ureters (unpaired
      Student's t test p = 0.004). Similarly the mean ratio of COX-2-to-glyceraldehyde
      3-phosphate dehydrogenase protein on immunoblotting was 0.15 +/- 0.02 in the 8
      normal ureters compared with 0.59 +/- 0.10 in the 6 obstructed ureters (p =
      0.003). CONCLUSIONS: These data indicate that COX-2 mRNA and protein levels are
      up-regulated in chronically obstructed human ureters. Using selective COX-2
      inhibitors may be useful for treating prostanoid induced effects associated with
      ureteral obstruction.

PMID- 12187273
TI  - Intravesical adenosine triphosphate stimulates the micturition reflex in awake,
      freely moving rats.
AB  - PURPOSE: Adenosine triphosphate (ATP) (Sigma Chemical Co., St. Louis, Missouri)
      is known to contract animal as well as human detrusor muscle and recent
      investigations have shown an involvement of ligand gated purinergic-1 receptors
      in detrusor contraction. In addition, ligand gated purinergic-3 receptors have
      been demonstrated on suburothelial sensory nerves (C-fibers) and may be involved
      in distention induced initiation of the micturition reflex. We tested the
      hypothesis that ATP given intravesically can stimulate afferent nerves and
      initiate the micturition reflex. MATERIALS AND METHODS: Continuous cystometry was
      performed in conscious, freely moving, normal female Sprague-Dawley rats.
      Cystometric parameters were evaluated before and after drug administration.
      RESULTS: Instilled intravesically ATP (10 mM.) induced bladder overactivity in 6
      animals with a mean increase in voiding pressure plus or minus standard error of
      73 +/- 9 to 107 +/- 9 cm. water (p <0.01), mean baseline pressure increase of
      5.32 +/- 0.58 to 12.71 +/- 1.01 cm. water (p <0.01) and mean bladder capacity
      decrease of 1.13 +/- 0.25 to 0.75 +/- 021 ml. (p <0.01). Lower concentrations had
      no significant effect. The effects of ATP were abolished by pretreatment with the
      ganglion blocker hexamethonium (40 mg./kg. ), nitric oxide synthase substrate L
      arginine (Sigma Chemical Co.) (200 mg./kg. ) and neurokinin-2 receptor antagonist
      123 (S)-N-methyl-N 123 4-(acetylamino-4-phenyl piperidone)-2-(3,4-dichlorophenyl)
      butyl 125 benzamide (Molecular Probes, Leiden, The Netherlands) (4 nmol.) given
      intravenously, the ligand gated purinergic-3 antagonist 2'-(or 3')-O
      (trinitrophyl)adenosine 5'-triphosphate (50 microM./kg.) given intravenously and
      the k channel opener ZD6169 given intravesically.(ATP). CONCLUSIONS: ATP given
      intravesically can induce bladder overactivity, probably by stimulating
      suburothelial C-fibers. The data suggest that several mediators and mechanisms
      are involved in mechano-afferent transduction in the bladder.

PMID- 12187274
TI  - The contractile potency of adenosine triphosphate and ecto-adenosine
      triphosphatase activity in guinea pig detrusor and detrusor from patients with a
      stable, unstable or obstructed bladder.
AB  - PURPOSE: We compared the potency of adenosine triphosphate (ATP) and its
      nonhydrolyzable analogue alpha,beta-methylene ATP for generating contractions in
      human detrusor smooth muscle from patients with a stable, unstable and obstructed
      bladders. The different ATP potencies were compared with the ecto-adenosine
      triphosphatase (ATPase) of these samples. MATERIALS AND METHODS: Contractile
      experiments were done in vitro by superfusing samples with purines and dose
      response curves were generated. Ecto-ATPase activity was measured from the rate
      of ATP hydrolysis sensitive to the ecto-ATPase inhibitor ARL 67156 with a
      luciferin-luciferase assay. RESULTS: ATP generated contractions with a mean EC50
      of 933 microM. in tissue from stable bladders and was significantly more potent
      in tissue from unstable and obstructed bladders (EC50 141 and 172 microM.,
      respectively). alpha,beta-methylene ATP was more potent in tissue from stable and
      unstable bladders (mean combined EC50 3 microM.). In guinea pig detrusor the mean
      EC50 for ATP and alpha,beta-methylene ATP was 138 and 5.5 microM., respectively.
      Mean total ATPase activity in unstable bladder biopsies plus or minus standard
      deviation was about 50% of that in stable bladder biopsies (2.54 +/- 1.50 versus
      1.37 +/- 0.46 nmol. per second per mg. protein ). The ARL 67156 sensitive
      fraction was also significantly less in samples from unstable compared with
      stable bladders (mean 0.94 +/- 0.41 versus 0.36 +/- 0.26 nmol. per second mg.
      protein ). CONCLUSIONS: The greater potency of ATP for generating contractions in
      detrusor from unstable bladders may be due to reduced extracellular hydrolysis,
      allowing purine greater access to detrusor smooth muscle. This finding may
      explain atropine resistant purine based contractions in detrusor from unstable
      bladders.

PMID- 12187275
TI  - Regional differences in bladder enlargement and in vitro contractility after
      outlet obstruction in the rabbit.
AB  - PURPOSE: Bladder outlet obstruction leads to bladder enlargement and subsequent
      decreases in contractile function in vivo and in vitro. We determined whether
      there were regional differences in bladder wall properties and in vitro
      contractile responses after 2 weeks of bladder outlet obstruction. MATERIALS AND
      METHODS: Male rabbits underwent cystometry. The bladder was then filled to 40 ml.
      and the surface was marked with 2-zero silk knots placed approximately 1 cm.
      apart. The distance between the knots was measured at 20, 40 and 80 ml. The
      animals then underwent the creation of surgical obstruction. After 2 weeks the
      obstruction was removed. Cystometry and measurements were repeated and strips
      were obtained from defined dorsal and ventral areas. Contractile responses to
      electrical field stimulation, adenosine triphosphate, carbachol and KCl were
      determined and compared with strips from unobstructed controls. RESULTS: In vivo
      expansion during bladder filling occurred evenly throughout the bladder wall in
      controls and the contractile response to all stimuli was similar in ventral and
      dorsal strips. After 2 weeks of bladder outlet obstruction the upper dome
      expanded to a significantly higher degree than the lower bladder body. The
      response to all stimuli was significantly reduced after bladder outlet
      obstruction and there was a significantly decreased response to all stimuli in
      dorsal compared with ventral strips. Strips from the dorsal midline showed a
      relaxation response to electrical field stimulation at low frequencies, whereas
      all ventral strips contracted. CONCLUSIONS: Functional remodeling after bladder
      outlet obstruction is a process that does not occur to the same extent throughout
      the bladder. The obstructed bladder is an inhomogeneous organ with significant
      regional differences in mechanical and pharmacological properties.

PMID- 12187276
TI  - Effects of selective beta2 and beta3-adrenoceptor agonists on detrusor
      hyperreflexia in conscious cerebral infarcted rats.
AB  - PURPOSE: We evaluated the effects of beta-adrenoceptor agonists on detrusor
      hyperreflexia in cerebral infarcted rats. MATERIALS AND METHODS: To produce
      cerebral infarction in Sprague-Dawley rats the left middle cerebral artery was
      occluded by introducing a monofilament nylon thread into the artery. In sham
      operated rats the same artery was exposed but not occluded. After these
      operations cystometric and cardiovascular experiments were performed with no
      anesthesia or restraint. RESULTS: After the operation bladder capacity was
      significantly decreased and voiding pressure was significantly increased in
      cerebral infarcted but not in sham operated animals. The difference in cerebral
      infarcted and sham operated rats was significant for each parameter (p <0.01).
      Post-void residual urine volume was not affected in either group. In the cerebral
      infarction group intravenous administration of CL316243 ([R,R]-5-2-[[2-(3
      chlorophenyl-2-hydroxyethyl]-amino]propyl] -1,3-benzodioxole-2,2-dicarboxylate)
      (Kissei Central Laboratories, Hotaka, Japan) a selective beta3-adrenoceptor
      agonist, significantly increased bladder capacity at 10 and 100 microgram./kg.
      without affecting voiding pressure or post-void residual urine volume.
      Procaterol, a selective beta2-adrenoceptor agonist, significantly increased
      bladder capacity and post-void residual urine volume at 10 microgram/kg.
      intravenously without affecting voiding pressure. In separate experiments
      procaterol (1 to 100 microgram./kg. intravenously) decreased mean blood pressure
      and increased heart rate in a dose dependent manner. In contrast, the effects of
      CL316243 (0.1 to 100 microgram./kg. intravenously) on mean blood pressure and
      heart rate were minimal. CONCLUSIONS: These results indicate that in cerebral
      infarcted rats detrusor hyperreflexia can be suppressed by the selective beta3
      adrenoceptor agonist CL316243 without increasing post-void residual volume and
      without significant cardiovascular side effects. If the current results hold true
      in humans, selective beta3-adrenoceptor agonists may prove useful for treating
      detrusor hyperreflexia associated with cerebral infarction.

PMID- 12187277
TI  - Modulation of insulin-like growth factor-I system of the bladder using a
      somatostatin analogue in chronic spinalized rats.
AB  - PURPOSE: We have previously reported the possible role of the insulin-like growth
      factor-I (IGF-I) system of mitogens in the development of detrusor smooth muscle
      hyperplasia and hypertrophy after spinal cord injury. We evaluated the in vivo
      effects of the anti-growth factor somatostatin analogue octreotide on the IGF-I
      system as well as subsequent changes in bladder smooth muscle hypertrophy and
      function after spinal cord injury in rats. MATERIALS AND METHODS: Included in
      this study were 90 adult female Sprague-Dawley rats weighing 200 to 250 gm. Of
      the rats 18 served as sham operated controls, while the remaining 72 underwent
      were spinal cord transection at the level of the T10 vertebra. The spinalized
      animals were randomly divided into 4 equal groups of 18, of which 1 group served
      as paraplegic controls. The other 3 groups received octreotide (60 microgram.
      daily for 4 weeks) delivered via a subcutaneously implanted osmotic pump
      immediately, 2 and 4 weeks after spinal cord injury. At the end of the experiment
      (6 to 8 weeks) each group of animals was subdivided into 2 subgroups of 9. In the
      first group filling cystometrography was done, while in the second subgroup wet
      bladder weight was estimated and Northern blot analysis was performed. RESULTS:
      Mean wet bladder weight plus or minus standard deviation in sham operated and
      paraplegic controls was 0.11 +/- 0.01 and 0.64 +/- 0.33 gm., respectively (p
      <0.05). The increase in bladder weight in paraplegic controls was associated with
      over expression of the IGF-I gene and with marked suppression of IGF binding
      proteins-3 and 5 compared with sham operated controls. On the other hand, mean
      wet bladder weight in the animals that received octreotide immediately after
      spinal cord injury was 0.17 +/- 0.02 gm., which was associated with a dramatic
      decrease in IGF-I gene expression and increased expression of IGF binding
      proteins-3 and 5. Mean cystometric bladder capacity in paraplegic controls was
      0.48 +/- 0.18 ml. with an associated voiding pressure of 71 +/- 13 cm. water. All
      paraplegic controls showed detrusor hyperreflexia. In animals that received
      octreotide immediately after spinal cord injury mean cystometric bladder capacity
      was 2.49 +/- 1.75 ml. with an associated voiding pressure of 32 +/- 7 cm. water.
      Detrusor hyperreflexia disappeared in 88.89% of the rats in this group. There
      were less marked changes in bladder weight (mean 0.24 and 0.29 +/- 0.3 gm.), IGF
      I gene expression and its binding proteins and urodynamic parameters when the
      drug was given 2 and 4 weeks, respectively, after spinal cord injury.
      CONCLUSIONS: Modulating the IGF-I system of mitogens in detrusor smooth muscle
      with consequently decreased bladder hypertrophy and improved urodynamic behavior
      in spinal cord injured animals using somatostatin analogue could be a possible
      therapeutic modality in patients with spinal cord injury.

PMID- 12187278
TI  - Diabetic cystopathy correlates with a long-term decrease in nerve growth factor
      levels in the bladder and lumbosacral dorsal root Ganglia.
AB  - PURPOSE It has been proposed that a deficiency in the axonal transport of nerve
      growth factor (NGF) may have an important role in inducing diabetic neuropathy,
      which contributes to diabetic cystopathy. Therefore, in streptozotocin (Sigma
      Chemical Co., St. Louis, Missouri) induced diabetic rats we investigated the
      relationship of bladder function with NGF levels in the bladder and lumbosacral
      dorsal root ganglia, which contain afferent neurons innervating the bladder.
      MATERIALS AND METHODS At 6 and 12 weeks after the induction of diabetes with
      streptozotocin (65 mg./kg. intraperitoneally) the effects of diabetes on Adelta
      afferent fiber dependent, conscious voiding were evaluated by metabolic cage
      measurements and awake cystometry. The effects of diabetes on C-fiber mediated
      bladder nociceptive responses were also investigated by cystometry with
      intravesical instillation of 0.25% acetic acid in the rats under urethane
      anesthesia. NGF levels in the bladder and L6 to S1 dorsal root ganglia were
      measured by enzyme-linked immunosorbent assay 3, 6, 9 and 12 weeks after
      streptozotocin injection. RESULTS In diabetic rats NGF levels in the bladder and
      L6 to S1 dorsal root ganglia were significantly decreased 12 weeks after
      streptozotocin injection (p <0.01). In cystometry and metabolic cage studies
      bladder capacity and post-void residual volume were significantly increased 12
      weeks after streptozotocin injection (p <0.01). Bladder nociceptive responses
      revealed by a reduction in inter-contraction intervals after acetic acid infusion
      were significantly decreased in a time dependent manner 12 weeks after
      streptozotocin injection.CONCLUSIONS Rats with streptozotocin induced diabetes
      mellitus showed a significant time dependent decrease in NGF levels in the
      bladder and L6 to S1 dorsal root ganglia that was associated with voiding
      dysfunction attributable to defects in Adelta and C-fiber bladder afferents.
      Therefore, reduced production of NGF in the bladder and/or impaired transport of
      NGF to L6 to S1 dorsal root ganglia, which contain bladder afferent neurons, may
      be an important mechanism inducing diabetic cystopathy.

PMID- 12187279
TI  - The effect of ovariectomy and long-term estrogen replacement on bladder structure
      and function in the rat.
AB  - PURPOSE The use of estrogen replacement therapy for treating postmenopausal
      urinary incontinence is a controversial topic. We examined the behavioral,
      cystometric and histological changes that occur with long-term estrogen depletion
      and supplementation in rat bladders to determine the role of menopause in lower
      urinary tract dysfunction. MATERIALS AND METHODS A total of 40 female Sprague
      Dawley rats were placed into 1 of 3 groups, including bilateral ovariectomy,
      bilateral ovariectomy plus estrogen replacement and control. The estrogen
      replaced group received a 0.25 mg. 16-week sustained release pellet (Innovative
      Research of America, Sanasota, Florida) placed subcutaneously. After surgery
      voiding frequency and volume were measured in 24-hour periods by placing animals
      in metabolic cages. After 16 weeks the rats underwent catheterization and
      continuous cystometry. The bladder was then removed and stained with Gomori
      trichrome. The collagen-to-smooth muscle density ratio was calculated for each
      specimen using current imaging software. RESULTS There was no significant
      difference in voiding patterns in the 3 groups, as measured by volume and voiding
      frequency. Cystometric data showed a trend toward higher voiding pressure,
      threshold pressure, baseline pressure and mean inter-voiding pressure in the
      ovariectomy group compared with the estrogen and control groups, although there
      was no statistical significance. Histological studies showed a higher mean
      collagen-to-smooth muscle ratio plus or minus standard deviation in the
      ovariectomy group (0.807 +/- 0.204) than in the ovariectomy plus estrogen
      replacement (0.709 +/- 0.118) and control (0.700 +/- 0.129) groups (p <0.05).
      Furthermore, when histological and cystometric data were compared for individual
      samples, we found a direct correlation of mean inter-voiding pressure (a measure
      of bladder instability) with the collagen-to-smooth muscle ratio (p <0.05).
      CONCLUSIONS Long-term estrogen replacement is beneficial for treating
      postmenopausal urinary incontinence.

PMID- 12187280
TI  - Diabetes induced alteration of clitoral hemodynamics and structure in the rabbit.
AB  - PURPOSE: We investigated the effect of diabetes on clitoral hemodynamics and
      structures in the rabbit. MATERIALS AND METHODS: A total of 25 New Zealand White
      female rabbits weighing 3 to 3.5 kg. were divided into 2 groups, including 5 in
      the control and 20 in the experimental group. Experimental animals received
      intravenous injection of alloxan hydrochloride (Sigma Chemical Co., St. Louis,
      Missouri) (100 mg./kg.). The development of diabetes was verified by measuring
      body weight and blood glucose levels. After 12 weeks clitoral cavernous blood
      flow in ml. per minute per 100 gm. tissue was measured with a laser Doppler
      flowmeter. Cross sections of the clitoris were used for histochemistry and
      histomorphometric image analysis. RESULTS: After 12 weeks 5 animals were included
      in the diabetes group. Mean baseline flaccid and peak clitoral cavernous blood
      flow plus or minus standard deviation significantly decreased in the diabetic
      group compared with the control group (3.9 +/- 1.6 and 5.8 +/- 2.2 versus 7.2 +/-
      2.5 and 12.9 +/- 5.8 ml. per minute per 100 gm. tissue, respectively, p <0.05).
      Histology revealed diffuse clitoral fibrosis in the diabetic group. On
      histomorphometry the mean proportion of clitoral cavernous smooth muscle in the
      diabetic group was significantly decreased compared with the control group (51.9%
      +/- 4.9% versus 62.3% +/- 3.1%, p < 0.05). CONCLUSIONS: These results show that
      diabetes mellitus produces significant adverse effects on the hemodynamic
      mechanism of clitoral engorgement and leads to diffuse clitoral cavernous
      fibrosis. It implies that decreased sexual arousal in diabetic women may result
      from structural changes in the clitoris.

PMID- 12187281
TI  - Activation of mitogen activated protein kinases and apoptosis of germ cells after
      vasectomy in the rat.
AB  - PURPOSE: Vasectomy induces a large amount of germ cell apoptosis. We examined the
      activation of mitogen activated protein kinases (MAPKs) in association with the
      apoptosis and proliferation of germ cells after vasectomy in the rat. MATERIALS
      AND METHODS: Eight-week-old Wistar rats underwent bilateral vasectomy and the
      testes were harvested 1 to 9 days after vasectomy. Germ cell apoptosis was
      evaluated by terminal deoxynucleotidyl transferase mediated deoxyuridine
      triphosphate nick end labeling and electrophoretic assay of DNA fragmentation.
      Western blotting and immunohistochemistry were used to examine the temporal and
      spatial activation of signal regulated kinases 1/2, c-Jun-terminal kinases 1/2
      and p38. Phospho-specific MAPK antibodies were used to examine their activations.
      Proliferation of germ cells was evaluated by proliferative nuclear cell antigen
      expression. RESULTS: Germ cell apoptosis was detected predominantly in primary
      spermatocytes with a peak 7 days after vasectomy. Signal regulated kinases 1/2, c
      Jun-terminal kinases 1/2 and p38 were constitutively expressed in the control
      testis. Western blotting and immunohistochemistry showed rapid activation of
      signal regulated kinases 1/2, followed by activation of c-Jun-terminal kinases
      1/2 and p38. Immunohistochemical study demonstrated the temporal and spatial
      relationships of apoptosis and MAPK activation in primary spermatocytes. On the
      other hand, proliferating cell nuclear antigen expression was enhanced in
      tetraploid spermatocyte and spermatogonia maximally 5 days after vasectomy.
      CONCLUSIONS: MAPKs were rapidly activated after vasectomy and germ cell apoptosis
      was observed after vasectomy. In contrast to the delayed phase up to 24 weeks
      after vasectomy, we observed hyperdynamic cellular turnover, spermatocyte loss
      through apoptosis and enhanced germ cell proliferation transiently at the early
      phase after vasectomy.

PMID- 12187282
TI  - Recovery of spermatogenesis by high dose gonadotropin-releasing hormone analogue
      treatment in rat cryptorchid testis after orchiopexy.
AB  - PURPOSE: Cryptorchidism is an adverse condition of spermatogenesis in many
      mammals. Surgical cryptorchidism in rats lasting more than a few weeks is so
      detrimental that spermatogenesis cannot be completely recovered even after
      orchiopexy. We evaluated the efficacy of the high dose gonadotropin-releasing
      hormone (Gn-RH) agonist leuprorelin acetate on damaged spermatogenesis in rat
      cryptorchid testes. MATERIALS AND METHODS: Male Fisher rats were divided into 2
      groups of 6 each and bilateral cryptorchidism was artificially produced. Five
      weeks later all rats underwent bilateral orchiopexy. One group served as the
      control, while the other received Gn-RH agonist injections at orchiopexy and 4
      weeks later. The animals were sacrificed 15 weeks after orchiopexy. The weight of
      the body, testis and epididymis was measured and the histology of spermatogenesis
      was examined. For statistical analysis the Student t test was applied. RESULTS:
      Testes in the Gn-RH group rats showed significant recovery of spermatogenesis up
      to complete spermatozoa formation, while those in control rats remained almost
      degenerated. The mean incidence of seminiferous tubules with recovered
      spermatogenesis plus or minus standard deviation was significantly higher in the
      Gn-RH than in the control group (87.8% +/- 6.0% versus 12.5% +/- 7.7%, p <0.001).
      CONCLUSIONS: Administering the high dose Gn-RH agonist leuprorelin acetate after
      orchiopexy greatly enhanced the recovery of spermatogenesis in rats. This finding
      is in accordance with other recent reports that treatment with Gn-RH analogues
      promotes the regeneration of once damaged spermatogenesis. On the other hand,
      these findings may cause one to question supplementation therapy now used in
      regular practice to boys with cryptorchidism.

PMID- 12187283
TI  - Keys to writing a competitive grant.

PMID- 12187284
TI  - Safety data required for proton-pump inhibitor use in children.

PMID- 12187285
TI  - Mechanisms of gastroesophageal reflux and gastroesophageal reflux disease.
AB  - Gastroesophageal reflux is a physiological phenomenon, occurring with different
      severity and duration in different individuals. Reflux occurs when this normal
      event results in the occurrence of symptoms/signs or complications. The
      pathophysiology of gastroesophageal reflux is complex and diverse, since it is
      influenced by factors that are genetic, environmental (e.g., diet smoking),
      anatomic, hormonal, and neurogenic. However, many mechanisms remain incompletely
      understood. Future research should focus on a better understanding of the
      physiology of the upper and lower esophageal sphincters, and of gastric motility.
      The afferent and efferent neural pathways and neuropharmacologic mediators of
      transient lower esophageal sphincter relaxations and gastric dysmotility require
      further study. The role of anatomic malformations such as hiatal hernia in
      children has been underestimated. While therapeutic possibilities are greater in
      number and largely improved, the outcomes of some treatments are far from
      satisfactory in many cases. In addition to development of new forms of treatment,
      research should address better use of currently available medical and surgical
      treatments.

PMID- 12187286
TI  - Are there beneficial effects of rapid introduction of enteral feeding in very low
      birth-weight infants, even in those with severe intra-uterine growth retardation
      (IUGR)?

PMID- 12187287
TI  - Contribution of endothelin-1 to the circulatory and renal abnormalities in
      patients with cirrhosis and portal hypertension.

PMID- 12187288
TI  - Early feeding advancement in very low-birth-weight infants with intrauterine
      growth retardation and increased umbilical artery resistance.
AB  - BACKGROUND: To investigate whether intrauterine growth retardation (birth weight
      <10th percentile), increased umbilical artery resistance (resistance index >90th
      percentile measured by Doppler velocimetry), or brain sparing (increased
      umbilical artery resistance and decreased middle cerebral artery resistance index
      <5th percentile) were associated with early feeding intolerance in very low-birth
      weight (VLBW, <1,500 g) infants. METHODS: From July 1999 to December 2000, 124
      inborn VLBW infants were enrolled in a prospective trial evaluating early enteral
      nutrition after a standardized feeding protocol (daily feeding advancement, 16
      mL/kg birth weight). Feeding tolerance was assessed as the age at which full
      enteral feeds (150 mL/kg daily) were achieved. Data are shown as median, 25th,
      and 75th percentiles. RESULTS: Full enteral feeds were achieved at 15 days
      (range, 12-21 days) of age for all infants. Intrauterine growth retardation (full
      enteral feeding achieved at 14 days; range, 12-21 days), increased umbilical
      artery resistance (full enteral feeding achieved at 14 days; range, 11-16 days),
      and brain sparing (full enteral feeding achieved at 15 days; range, 14-20 days)
      were not associated with early feeding intolerance. CONCLUSION: Very low-birth
      weight infants with intrauterine growth retardation, increased umbilical artery
      resistance, and brain sparing tolerated enteral feeding as well as appropriate
      for-gestational-age VLBW infants.

PMID- 12187290
TI  - Indomethacin, dexamethasone, and intestinal damage in infant rats.
AB  - BACKGROUND: Indomethacin is commonly used in the Neonatal Intensive Care Unit to
      induce closure of the patent ductus arteriosus and to prevent intraventricular
      hemorrhage. It is known that indomethacin causes intestinal ulceration in adults,
      but its effect in infants is less clear. In a preliminary experiment, it was
      found that the administration of 10 mg/kg/d of indomethacin, a dose that damages
      the adult rat intestine, had no detrimental effects on newborn suckling rats
      whereas dexamethasone at 0.25 mg/kg/d caused significant growth failure and
      villous blunting. It was then hypothesized that the lack of intestinal damage
      with indomethacin in infants was related to protection given by mother's milk.
      METHODS: Subsequent experiments were performed wherein 10 mg/kg/d of indomethacin
      was provided to infant mother-reared, infant artificially fed, and adult rats.
      The expression of intestinal cyclooxygenases in the prostaglandin synthetic
      pathway of control rats was examined to initiate an exploration into a mechanism
      for the developmental response to indomethacin. RESULTS: Mother-reared and
      artificially fed infant rats demonstrated resistance to the ulcerogenic effects
      of indomethacin, in contrast to the adults. A differential presence of
      cyclooxygenase-1 and cyclooxygenase-2 was not distinctly seen between infancy and
      adulthood. CONCLUSIONS: The results indicate that a varying response to the
      damaging effects of indomethacin on the intestine occurs during development with
      the infant being less susceptible than the adult. This differed from the effects
      of dexamethasone administration, which caused significant intestinal atrophy in
      the infant rats. The intestinal protection to the effects of indomethacin in
      infants is not dependent on mother's milk or a developmental difference in the
      prostaglandin biosynthetic pathway.

PMID- 12187289
TI  - Plasma endothelin-1 concentrations in children with cirrhosis and their
      relationship to renal function and the severity of portal hypertension.
AB  - BACKGROUND: Plasma endothelin-1 (ET-1) is a potent vasoconstrictor peptide
      involved in the pathogenesis of several disorders. Endothelin-1 concentrations
      are increased in adult patients with cirrhosis. However, little is known about ET
      1 concentrations in children with cirrhosis. METHODS: Radioimmune assay was used
      to measure plasma ET-1 concentrations in 19 children with cirrhosis (8 patients
      with ascites, and 11 without ascites), and 11 age- and sex-matched healthy
      children. The plasma ET-1 concentrations were correlated with the mean blood
      pressure, creatinine clearance, and severity of portal hypertension, as measured
      by portal flow volume and portal flow velocity. RESULTS: Patients with cirrhosis
      and ascites had increased plasma ET-1 concentrations compared with patients who
      did not have ascites (6.8 pg/mL +/- 0.62 pg/mL vs. 4.6 pg/mL +/- 0.35 pg/mL; mean
      +/- SEM; < 0.01) and controls (3.6 pg/mL +/- 0.27 pg/mL; mean +/- SEM; < 0.0005).
      Plasma ET-1 concentrations were higher in patients with cirrhosis who did not
      have ascites compared with controls ( < 0.005). No significant differences were
      observed between concentrations of the patients with cholestasis and those
      without cholestasis (5.4 pg/mL +/- 0.52 pg/mL vs. 5.2 +/- 0.32 pg/mL; mean +/-
      SEM; = 0.1). Plasma ET-1 concentrations correlated positively with the mean blood
      pressure ( = 0.58; < 0.05) and negatively with renal function, as measured by
      creatinine clearance ( = -0.7; <0.005). However, no correlation was detected
      between ET-1 concentrations and portal flow volume ( = -0.02; = 0.4) or portal
      flow velocity ( = -0.16; = 0.4). CONCLUSIONS: Plasma ET-1 concentrations are
      increased in children with cirrhosis, with or without ascites, compared with
      controls. Patients with cirrhosis and ascites have increased ET-1 concentrations
      compared with those without ascites. The degree of increase does not relate to
      the severity of portal hypertension. This increase tends to maintain systemic
      blood pressure but is associated with a decrease in renal function.

PMID- 12187292
TI  - Use of quantitative ultrasound to assess osteopenia in children with Crohn
      disease.
AB  - BACKGROUND AND AIMS: Children with Crohn disease are at increased risk for
      osteopenia and osteoporosis. Early development of osteopenia can increase the
      lifetime risk for fractures and may be amenable to early intervention. The gold
      standard for measuring bone mineral density (BMD) and fracture risk is dual x-ray
      absorptiometry (DXA), but this involves some radiation and specialized programs
      for measuring BMD in children. Bone density Z scores were evaluated with
      quantitative ultrasound (QUS) using a novel portable device and were compared
      with DXA in children with Crohn disease. METHODS: Thirty-five children with
      documented Crohn disease (mean age 14.3 +/- 2.3 years) had speed of sound
      measured at the left radius and left tibia. Normative values for QUS Z scores
      were calculated from a cohort of 1,110 healthy children. A subgroup of 26
      children with Crohn disease underwent both QUS and DXA. Z scores were calculated
      and compared for both groups. RESULTS: The mean Z score using lumbar spine DXA
      was -1.04 +/- 1.51 SD, compared with -0.15 +/- 1.49 SD, using the lowest Z score
      for QUS ( < 0.05). Using height adjusted DXA, 50% of children with Crohn disease
      had osteopenia, whereas QUS detected only 19.2% of these children ( < 0.05).
      Significantly fewer cases of osteopenia were detected using QUS at Z scores up to
      -2 SD. CONCLUSIONS: Quantitative ultrasound performed on the radius and tibia may
      not be sensitive enough to pick up osteopenia in children with Crohn disease.

PMID- 12187291
TI  - Supplementation of infant formula with the probiotic lactobacillus reuteri and
      zinc: impact on enteric infection and nutrition in infant rhesus monkeys.
AB  - Gut colonization by may have beneficial effects on infant health or capacity to
      resist infectious disease. Zinc supplementation has also been proposed to
      increase infants' resistance to disease; however, many studies have yielded
      conflicting results. OBJECTIVES: To study effects of probiotic supplementation of
      infant formula (with or without supplemental zinc) on nutritional status, gut
      colonization and the ability to resist gastrointestinal infection in an infant
      rhesus monkey model. METHODS: Infant monkeys were fed control infant formula (5
      mg Zn/L), control formula with or control formula with and supplemental zinc (15
      mg Zn/L) from birth to 4 months. Growth, nutritional status, mineral absorption,
      intestinal colonization and frequency and severity of enteropathogenic -induced
      gastroenteritis were monitored. RESULTS: Gastrointestinal colonization was
      achieved and was associated with increased ileal villous surface area and
      improved hematocrit, with no adverse effects on growth or nutritional indices.
      Fortification to 15 mg Zn/L reduced plasma copper, erythrocyte Cu/Zn-superoxide
      dismutase, hemoglobin, and iron absorption. Infants fed -supplemented formula had
      reduced diarrhea severity throughout the study period and recovered more rapidly
      from acute diarrhea than the other groups. CONCLUSION: -supplementation of infant
      formula is safe, improves iron status and decreases diarrhea severity in infant
      rhesus monkeys and thus may help protect formula-fed human infants from infection
      and nutritional deficiencies.

PMID- 12187293
TI  - Esophageal Acid clearance: more volume-dependent than motility-dependent in
      healthy piglets.
AB  - BACKGROUND/AIMS: The present study investigates manometrically in healthy piglets
      whether esophageal clearance after distension with different volumes of acid is
      volume-dependent. METHODS: Sedated, non-intubated piglets (n = 22) underwent
      stationary manometry of the esophagus with a 4-probe perfused assembly after
      successive injection of 1, 2, and 3 mL of saline and acid. Simultaneous pH
      metering allowed assessment of acid clearance. Wave features and clearance times
      after saline and acid were compared by paired non-parametric tests and Friedman
      analysis of variance. The linearity of the relationships between the clearance
      times and the volumes of acid infused were tested after square root
      transformations by one-way ANOVA repeated measures. The significance level was
      set at < 0.05. RESULTS: The motor response was identical after distension with
      saline and acid except for the largest amount of acid used, which elicited more
      waves during the first 5 minutes after infusion. Time elapsed until regaining pH4
      was longer after higher amounts of acid, but not significantly, whereas that
      necessary to regain baseline pH was significantly longer after such challenge.
      Esophageal motility was practically identical after 1 and 2 mL of acid, but it
      was slightly less effective in the first minute after the 3 mL challenge. There
      was a linear correlation between clearance times and volumes of acid infused.
      CONCLUSIONS: Up to a certain volume, the motor responses of the healthy esophagus
      to distension with neutral or acid fluids were similar. Acid clearance was more a
      function of the amount of acid present than of the motor response elicited by its
      presence. Only when the amount of acid was large, esophageal motor response was
      worse than that elicited after equivalent volumes of neutral fluid. The present
      evidence suggests that long episodes of reflux in pH tracings might reflect large
      volumes of refluxate as well as disturbed motor function.

PMID- 12187294
TI  - Influence of dietary cholesterol on vitamin d metabolism in formula-fed preterm
      neonates.
AB  - OBJECTIVES: Supplementation of preterm formulas with cholesterol could help to
      mimic the fat composition of human milk. However, this could possibly influence
      vitamin D 25-hydroxylation because this reaction is catalyzed in part by the
      mitochondrial cytochrome P-450, the enzyme responsible for the 27-hydroxylation
      of cholesterol. The purpose of this study was to verify whether the addition of
      cholesterol to preterm formulas could interfere with vitamin D metabolism in
      preterm neonates. METHODS: In a prospective study, 30 preterm neonates were
      randomly assigned to a low (< 0.03 g/L), medium (0.15 g/L), or high (0.30 g/L)
      cholesterol-content preterm formula until theoretical term (i.e., 40 weeks post
      conceptional age). Anthropometric data and serum hydroxy-vitamin D and 1,25
      dihydroxy-vitamin D concentrations were measured at study entry and theoretical
      term. In a subgroup of 14 subjects, serum cholesterol and lymphocyte 3-hydroxy-3
      methylglutaryl coenzyme A reductase mRNA were also assessed. RESULTS: (median
      [25, 75 centiles]): At theoretical term, there were no significant differences in
      serum hydroxy-vitamin D concentrations among the three groups, even after
      adjustment for confounding variables (65 [50, 78] nmol/L, 79 [59, 86] nmol/L, and
      67 [43, 103] nmol/L, respectively, = 0.65) or 1,25 dihydroxy-vitamin D ( = 0.88).
      Furthermore, there were no significant differences in 3-hydroxy-3-methylglutaryl
      coenzyme A reductase mRNA copy numbers. CONCLUSIONS: In preterm neonates fed
      formulas with a cholesterol content similar to or higher than that of human milk,
      we did not observe deleterious effects on vitamin D metabolism. However, long
      term effects of cholesterol supplementation require further studies.

PMID- 12187295
TI  - Effect of Ursodeoxycholic Acid on the Expression of the Hepatocellular Bile Acid
      Transporters (Ntcp and bsep) in Rats With Estrogen-Induced Cholestasis.
AB  - OBJECTIVES: Rats with ethinyl estradiol-induced cholestasis have a decreased bile
      flow and a decreased expression of basolateral and canalicular hepatocyte
      membrane transporters. The bile acid ursodeoxycholic acid improves bile flow in
      these animals. The purpose of this study was to examine the effect of
      ursodeoxycholic acid on the expression of hepatocellular bile acid carriers.
      METHODS: Rats received either ethinyl estradiol (5 mg.kg body wt. for 10 days) or
      ethinyl estradiol associated with ursodeoxycholic acid (1% in the diet). A third
      group of rats received ursodeoxycholic acid alone. Bile flow, bile acid, and
      glutathione biliary outputs were measured. Messenger RNA levels and protein
      expression of Na -dependent taurocholate co-transporting polypeptide, and bile
      salt export pump were determined in basolateral and canalicular membrane
      preparations by Northern and Western blot analysis. RESULTS: Ursodeoxycholic acid
      restored bile flow in ethinyl estradiol-treated rats by increasing bile acid
      secretion. It did not improve glutathione output nor bile acid-independent flow.
      Na -dependent taurocholate co-transporting polypeptide mRNA and protein were
      decreased by ethinyl estradiol and not restored by ursodeoxycholic acid. In
      contrast, canalicular bile salt export pump protein expression was decreased by
      ethinyl estradiol and fully restored to control levels by ursodeoxycholic acid.
      CONCLUSIONS: Ursodeoxycholic acid increases bile flow in ethinyl estradiol
      treated rats by increasing bile acid secretion. This increase is possibly
      mediated by a normalization of the expression of the canalicular bile salt export
      pump.

PMID- 12187296
TI  - Mechanisms of vitamin B(12) absorption in breast-fed infants.
AB  - OBJECTIVES: The mechanisms of vitamin B(12) absorption in infants are unknown. We
      investigated whether haptocorrin (HC), a vitamin B(12) -binding protein in human
      milk, facilitates vitamin B(12) absorption during the neonatal period or if it
      occurs by a process similar to that in adults involving another vitamin B(12) 
      binding protein, intrinsic factor (IF). METHODS: To determine whether HC or IF
      can deliver vitamin B(12) to the enterocyte, binding studies using Caco-2
      intestinal cells in culture and purified human milk HC-[ (57)Co]vitamin B(12) or
      [(125)I]IF-vitamin B(12) were performed. Determination of IF secretion by infant
      stomach was investigated by a competitive ELISA on fecal extracts from breast-fed
      infants. Determination of receptors specific for IF-vitamin B(12) or HC-vitamin
      B(12) in infant intestine was achieved by ligand blot analysis using isolated
      brush border membrane vesicles (BBMV) from fetal and adult intestine and Caco-2
      cells. PCR was performed to identify the IF receptor gene transcript in Caco-2
      cells and fetal intestine. RESULTS: Limited binding of both HC and IF to Caco-2
      cells was observed; however, HC displayed affinity to low molecular weight
      proteins in BBMV from fetal intestine and Caco-2 cells while IF showed affinity
      for a 240 kDa protein in BBMV from fetal intestine and Caco-2 cells. IF receptor
      gene transcript was identified in fetal intestine and Caco-2 cells. An increase
      in IF excretion from breast-fed infants throughout early life was observed.
      CONCLUSIONS: An IF-dependent vitamin B(12) absorption mechanism appears to be in
      place in breast-fed infants. However, IF levels may be too low in early life to
      participate in vitamin B(12) absorption; therefore, haptocorrin may mediate
      vitamin B(12) absorption until the absorption function can be taken over by a
      more mature IF system.

PMID- 12187297
TI  - Water load test in children.
AB  - OBJECTIVE: The purpose of this study was to estimate values for the water load
      test in healthy elementary school children. METHODS: We measured the volume of
      water consumed by 176 children (71 boys and 105 girls) using the water load test
      at school. Children completed a questionnaire, which included self-efficacy and
      abdominal pain history. Then subjects drank water for 3 minutes or until full.
      RESULTS: Children drank 630 +/- 260 ml. Water consumption correlated with age,
      weight, and height. Children who believed they could drink a lot, drank more than
      those who thought they could not, < 0.01. CONCLUSION: The water load test is a
      simple and inexpensive method to estimate onset of satiety and may be useful in
      future studies now that there are values for healthy children.

PMID- 12187298
TI  - Comparison of steatocrit and fat absorption in persons with cystic fibrosis.
AB  - BACKGROUND: Exocrine pancreatic insufficiency is a common problem in persons with
      cystic fibrosis causing malabsorption and poor growth. The 72-hour fecal fat
      study is the best qualitative measure of fat malabsorption used in clinical
      practice. This test has several drawbacks, which include cost and logistics. The
      steatocrit has been proposed as a rapid method to assess fat malabsorption.
      OBJECTIVES: The objective of this study was to determine whether the steatocrit
      is an accurate estimation of fat malabsorption in persons with cystic fibrosis.
      METHODS: Forty-nine stool samples for steatocrit processing were obtained from 72
      hour fecal fat collections performed on twenty-seven persons with cystic
      fibrosis. Stools were weighed and homogenized with sand and water. The emulsified
      specimen was pipetted into heparinized capillary tubes and centrifuged for 15
      minutes. The length of the fatty layer was compared to the length of the solid
      layer plus the fatty layer in each tube to determine the steatocrit value. Four
      steatocrit mixtures were evaluated: (1) standard steatocrit, (2) dilute
      steatocrit, (3) acid steatocrit, (4) dilute acid steatocrit. Steatocrit values
      were compared with the coefficient of fat absorption determined from the 72-hour
      fecal fat collection. RESULTS: The correlation coefficient of the steatocrit and
      the coefficient of fat absorption ranged from -.045 to -.491. Only the
      coefficient of fat absorption and the acid steatocrit had a significant
      correlation ( = 0.033). CONCLUSION: The steatocrit is an imprecise measure of fat
      absorption and not clinically useful in estimating steatorrhea.

PMID- 12187299
TI  - Small bowel intestinal permeability in Australian aboriginal children.
AB  - OBJECTIVE: To show that the severity of diarrheal disease in Aboriginal children
      in tropical Australia is a consequence of underlying small intestinal mucosal
      damage. STUDY DESIGN: A prospective study of 338 Aboriginal admissions compared
      to 37 non-Aboriginal children, both diarrhea cases and controls. Intestinal
      permeability was measured by lactulose-rhamnose (L/R) ratios on a timed 90-minute
      blood test. RESULTS: For diarrheal admissions, significantly more Aboriginal (vs.
      non-Aboriginal children) had hypokalemia (70 vs. 10%), acidosis (65 vs. 29%),
      moderate to severe dehydration (52 vs. 19%) and a longer mean length of stay
      (mean 8.9 vs. 3.9 days). Mean L/R ratios (95% confidence intervals) in Aboriginal
      children (diarrhea vs. controls) were 16.5 (14.6-18.7) vs. 4.5 (3.8-5.3) compared
      to 7.7 (4.4-13.3) vs. 2.5 (1.8-3.4), respectively, in non-Aboriginals. Abnormal
      permeability ratios (> 5.6) consistent with tropical-environmental enteropathy
      syndrome were found in 36% (27/75) of Aboriginal controls compared to none of the
      non-Aboriginal controls. On multiple regression, the factors associated with high
      L/R ratios were diarrheal severity ( < 0.001), acidosis ( = 0.007) and
      hypokalemia ( = 0.04). CONCLUSIONS: An underlying tropical-environmental
      enteropathy contributes to the severity of acute gastroenteritis in Aboriginal
      children. Diarrheal complications, such as acidosis, hypokalemia, and osmotic
      diarrhea are associated with high L/R ratios, reflecting greater small intestinal
      mucosal damage.

PMID- 12187300
TI  - Hypertrophic osteoarthropathy in untreated ulcerative colitis.

PMID- 12187301
TI  - Difficult management choices for infants with short bowel syndrome and liver
      failure.

PMID- 12187302
TI  - Neonatal liver transplantation for fulminant hepatitis caused by herpes simplex
      virus type 2.

PMID- 12187303
TI  - Eosinophilic esophagitis associated with anastomotic strictures after esophageal
      atresia repair.

PMID- 12187304
TI  - Oral bile Acid treatment in two Japanese patients with Zellweger syndrome.

PMID- 12187305
TI  - Re: hepatocyte growth factor and inflammatory bowel disease.

PMID- 12187306
TI  - Helicobacter pylori may influence height in children independent of socioeconomic
      factors.

PMID- 12187307
TI  - Consumption of wheat foodstuffs not a risk for celiac disease occurrence in
      burkina faso.

PMID- 12187308
TI  - Concerns about experimental design.

PMID- 12187309
TI  - Difficulties in conducting large-scale studies on rare diseases: the case for
      pediatric hepatitis C infection.

PMID- 12187310
TI  - Part 1. Uric acid and losartan.
AB  - PURPOSE OF REVIEW: To characterize the mechanism and clinical impact of the
      angiotensin-receptor blocker losartan on both renal uric acid handling and
      thereby serum uric acid. RECENT FINDINGS: Losartan effect on serum uric acid has
      been demonstrated at various stages of renal failure including most recently
      observations obtained in end-stage renal disease patients. Other angiotensin
      receptor blockers do not alter renal handling of uric acid. The uricosuria, which
      accompanies losartan administration, has not been associated with adverse renal
      consequences, in part, because of the increase in urinary pH that follows its
      administration. SUMMARY: Hyperuricemia is closely linked to both hypertension and
      cardiovascular disease. The development of hyperuricemia and its persistence are
      clearly renal processes. Likewise, the correction of hyperuricemia is often
      accomplished by increasing its renal excretion. A number of medications, by way
      of varying mechanisms, can alter renal urate handling and thereby influence serum
      uric acid values. Most recently, the angiotensin-receptor blocker losartan has
      been shown to reduce serum uric acid. The mechanism of this process relates to
      losartan alone and does not involve the E-3174 metabolite of this compound. This
      probenecid-like effect of losartan occurs shortly after drug administration, and
      is both transient and dose-dependent. This property of losartan, touted by some
      as a meaningful pharmacological distinction among the angiotensin-receptor
      blockers, remains to be proved, since, to date, the hypothesis that a reduction
      in serum uric acid alters the natural history of cardiovascular disease has not
      been formally tested.

PMID- 12187311
TI  - The renal risks of smoking: an update.
AB  - PURPOSE OF REVIEW: Smoking increases the renal risk both in diabetic and in
      nondiabetic renal disease. The purpose of the present review is to summarize the
      current state of knowledge about this important remediable renal risk factor.
      RECENT FINDINGS: The deleterious effect of smoking on renal function extends
      beyond patients with primary or secondary renal disease and patients with a renal
      transplant, because recent studies document a relation between smoking and loss
      of filtration rate, even in cardiovascular high-risk populations without primary
      renal disease such as the elderly, the patient with severe essential
      hypertension, or the patient with widespread atherosclerosis. Furthermore, recent
      studies show that in nondiabetic patients without primary renal disease,
      albuminuria, a potential surrogate marker of glomerular damage, is correlated
      with smoking. The mechanisms underlying the adverse renal effects of smoking are
      still incompletely understood. Beyond its effect on progression of renal failure,
      smoking is also an important cardiovascular risk factor in the patient with renal
      failure or the patient with a renal transplant. SUMMARY: Smoking is one of the
      most important remediable renal risk factors. The exact mechanisms of smoking
      induced renal damage remain to be determined. For all the above reasons cessation
      of smoking should be recommended to renal patients - a recommendation which is
      infrequently given and even less frequently followed.

PMID- 12187312
TI  - Interactions between hypercholesterolemia and hypertension: implications for
      therapy.
AB  - PURPOSE OF THE REVIEW: The purpose of the present review is to summarize the
      available information that supports the therapeutic role for the concomitant and
      aggressive management of hypercholesterolemia and hypertension. RECENT FINDINGS:
      A concomitant management of hypertension and high-plasma cholesterol has been
      suggested to significantly reduce the extent of cardiovascular complications.
      Hydroxymethylglutaryl coenzyme A reductase inhibitors (statins) have been
      demonstrated to be very effective in the treatment of patients with
      hypercholesterolemia where they reduce the rate of coronary and cerebrovascular
      complications. This benefit is largely extended to the hypertensive population.
      Very recently some studies have demonstrated the capacity of statins to improve
      blood pressure control in patients with hypertension and this effect, which has
      not been demonstrated for the other lipid-lowering drugs, could be very important
      in the clinical management of overall cardiovascular risk. SUMMARY: These
      findings confirm that the prevention of cardiovascular diseases should be based
      on the aggressive treatment of many different risk factors. This is particularly
      true for patients with hypertension and hypercholesterolemia for whom the
      negative interaction between risk factors could be effectively managed by an
      appropriate choice of both antihypertensive and lipid-lowering drugs.

PMID- 12187313
TI  - Recent developments in the treatment of obesity-related hypertension.
AB  - PURPOSE OF REVIEW: Obesity is a major public health issue, and hypertension is
      one of the most common associated co-morbidities. Here, recent developments in
      the treatment of obesity-related hypertension, published during the past year,
      are reviewed. RECENT FINDINGS: Several recent studies have examined the effect of
      dietary and lifestyle changes on hypertension. These studies uniformly confirm
      that weight reduction together with salt restriction and increased physical
      exercise can lower blood pressure. Several studies have shown that
      pharmacologically induced weight reduction with orlistat or sibutramine can
      likewise be beneficial in the management of obese hypertensive patients. The role
      of surgery in obesity remains to be defined. SUMMARY: Both non-pharmacologically
      and pharmacologically induced weight loss can lower blood pressure in obese
      hypertensive patients. The effects of weight loss and pharmacological management
      on morbidity and mortality in obese hypertensive patients remains to be addressed
      in prospective trials.

PMID- 12187314
TI  - Acetylcysteine and contrast media nephropathy.
AB  - PURPOSE OF REVIEW: Radiographic contrast media are used at an increasing rate for
      several diagnostic and therapeutic applications. Therefore, contrast agent
      induced nephropathy will become more important, including the risk of patient
      impairment and costs. The prevention of radiographic contrast-induced nephropathy
      is mandatory. Radiographic contrast agent-induced nephropathy is caused by
      vasoconstriction-mediated renal medullary ischaemia and direct toxic damage to
      renal tubular epithelial cells. These effects may be partly mediated by the
      generation of reactive oxygen species. Data from experimental studies indicate
      that antioxidants, e.g. acetylcysteine, may prevent radiocontrast-induced
      nephropathy. RECENT FINDINGS: Two prospective, randomized, placebo-controlled
      studies in patients with moderate renal insufficiency confirmed that the
      prophylactic oral administration of acetylcysteine, at a dose of 600 mg twice a
      day along with hydration, prevents the reduction in renal function after
      radiocontrast administration. SUMMARY: The use of acetylcysteine together with
      hydration is the treatment of choice to protect against radiographic contrast
      media-induced nephropathy.

PMID- 12187315
TI  - Ambulatory blood pressure monitoring in chronic renal disease: technical aspects
      and clinical relevance.
AB  - PURPOSE OF REVIEW: To evaluate the current value of ambulatory blood pressure
      monitoring in patients with chronic renal disease and end-stage renal disease.
      RECENT FINDINGS: Ambulatory blood pressure monitoring has become an important
      tool in hypertension research and clinical practice. Its use in essential
      hypertension shows a strong predictive ability in the assessment of
      cardiovascular outcomes. In chronic renal failure and end-stage renal disease,
      the role of ambulatory blood pressure monitoring is still being actively
      evaluated, and available evidence shows that it is better than office blood
      pressure in predicting left ventricular hypertrophy and progression of renal
      dysfunction in patients with chronic renal failure. In end-stage renal disease,
      preliminary data suggest better prediction of mortality in hemodialysis patients
      in comparison with clinic blood pressures. The most conspicuous problems with the
      literature on this subject are small sample sizes and the paucity of longitudinal
      observational studies and intervention trials. SUMMARY: Preliminary data and
      extrapolations from essential hypertension have justified a growing excitement
      about the use of ambulatory blood pressure monitoring in renal disease. However,
      further research will have to address the limitations of the available literature
      before generalization of its use is implemented.

PMID- 12187317
TI  - Elucidating the structural basis of membrane transport protein function: light at
      the end of the channel?

PMID- 12187316
TI  - Pathogenesis and treatment of hypertension in polycystic kidney disease.
AB  - PURPOSE OF REVIEW: Hypertension is common in patients with autosomal dominant
      polycystic kidney disease. It may contribute to cardiovascular risk and to
      progression of renal failure. RECENT FINDINGS: Apart from fluid overload and
      renin activation, hypertensive patients with autosomal dominant polycystic kidney
      disease also have increased sympathetic activity, regardless of renal function.
      Sympathetic hyperactivity not only contributes to the hypertension but may also
      increase cardiovascular risk independent of blood pressure. SUMMARY: Treatment
      for normalizing blood pressure and sympathetic activity should be started early
      in the course of the disease.

PMID- 12187318
TI  - Physiological importance of endosomal acidification: potential role in proximal
      tubulopathies.
AB  - PURPOSE OF REVIEW: In recent years, there have been significant advances in our
      understanding of the molecular mechanisms relating proximal tubule abnormalities
      to the pathogenesis of renal Fanconi syndrome. This review focuses on the role of
      intra-endosomal acidification-machinery proteins (V-ATPase, CLC-5, NHE-3), as
      well as apical receptors (megalin and cubilin), in the receptor-mediated
      endocytosis pathway and in the pathogenesis of proximal tubulopathies. RECENT
      FINDINGS: Animal models, including CLC-5 and megalin knockout mice, cubilin
      deficient dogs and cadmium-toxicity studies in rats, have shed light on defects
      leading to low-molecular-weight proteinuria. In particular, the important
      contribution of defective endosomal acidification and membrane-protein recycling
      to the pathogenesis of the Fanconi syndrome has emerged from these studies. These
      observations, together with recent findings in patients with Dent's disease,
      Lowe's syndrome, autosomal-dominant idiopathic Fanconi syndrome and Imerslund
      Grasbeck disease, show that the proteinuria of the Fanconi syndrome is more
      generalized than previously suspected. High concentrations of polypeptides,
      including hormones, vitamin-binding proteins and chemokines in urine from these
      patients and animals may play an important role in the progressive renal failure
      that is associated with the syndrome. SUMMARY: The molecular mechanism of
      proximal tubule protein reabsorption, which is defective in renal Fanconi
      syndrome, includes a crucial role for endosomal acidification-machinery proteins,
      in particular the V-ATPase and CLC-5 chloride channels, in the trafficking and
      acidification-dependent recycling of apical membrane proteins, including the
      endocytotic receptors megalin and cubilin. An increased understanding of the
      roles of V-ATPase and CLC-5 in proximal tubule endosomal acidification, in the
      regulation of the megalin/cubilin-mediated endocytosis pathway and finally in the
      pathogenesis of human Fanconi syndrome will help in the devising of appropriate
      strategies for therapeutic intervention for this disorder.

PMID- 12187319
TI  - Do polycystins function as cation channels?
AB  - PURPOSE OF REVIEW: During the past 2 years growing evidence has emerged that
      polycystins (polycystin-1 and polycystin-2) are ion channels or regulators of ion
      channels. This suggests that autosomal-dominant polycystic kidney disease
      (ADPKD), which arises from mutations in polycystins, is a form of ion-channel
      disease (channelopathy). The present review addresses the properties and the mode
      of action of polycystin channels; it also discusses how polycystin channel
      signaling may be involved in cyst formation in ADPKD. RECENT FINDINGS: The
      precise functions of polycystin-1 and polycystin-2 are unclear. However, recent
      work has revealed that polycystin-1 may induce or modulate ion channels,
      including polycystin-2 channels, and that polycystin-2 functions as a calcium
      regulated, calcium-permeable cation channel on the endoplasmic reticulum or on
      the plasma membrane with polycystin-1. These data suggest that ion-channel
      signaling mediated by polycystins is important for tubule formation in kidney and
      that disrupted signaling results in cyst formation. SUMMARY: ADPKD is a systemic
      hereditary disease that is characterized by renal and hepatic cysts, and results
      in end-stage renal failure in 50% of affected individuals. Most cases (>95%) are
      caused by genetic mutations in either the PKD1 or the PKD2 gene, or both, which
      encode polycystin-1 and polycystin-2, respectively. The present review provides a
      hint of how malfunction of polycystins may give rise to cysts, based on recent
      observations concerning polycystin channels. Polycystin channel signaling may
      prove to be an important new target for therapy of ADPKD.

PMID- 12187320
TI  - New insights into phosphate homeostasis: fibroblast growth factor 23 and frizzled
      related protein-4 are phosphaturic factors derived from tumors associated with
      osteomalacia.
AB  - PURPOSE OF REVIEW: Studies of patients with tumors associated with osteomalacia
      (tumor-induced osteomalacia), X-linked hypophosphatemia (XLH) and autosomal
      dominant hypophosphatemic rickets have provided important new insights into the
      identity and mechanisms of action of factors that play a role in controlling
      renal phosphate excretion and serum phosphate concentrations. In the present
      review I discuss how these disorders may be mechanistically related to one
      another. RECENT FINDINGS: Patients (or mice) with these disorders manifest
      rickets as a result of excessive urinary phosphate losses. Tumors associated with
      osteomalacia elaborate factors ('phosphatonins') that increase renal phosphate
      excretion and reduce serum phosphate concentrations. These factors include
      fibroblast growth factor (FGF) 23 and frizzled-related protein-4. Mice with XLH
      (Hyp) elaborate a circulating factor that induces changes in mineral metabolism
      similar to those in patients with tumor-induced osteomalacia. In mice and humans
      with XLH, a mutant enzyme, phex/PHEX, cannot degrade the phosphaturic factor.
      Patients with autosomal-dominant hypophosphatemic rickets produce a mutant FGF 23
      that is resistant to proteolytic degradation. Excessive FGF 23 activity is
      associated with increased renal phosphate excretion and hypophosphatemia.
      SUMMARY: In tumor-induced osteomalacia, excessive production of factors such as
      FGF 23 and frizzled-related protein-4 is associated with inability of endogenous
      proteolytic enzymes to degrade these individual substances, with resultant
      hyperphosphaturia, hypophosphatemia, and rickets. In XLH, mutant PHEX/phex
      (phosphate-regulating gene with homology to endopeptidases located on the X
      chromosome) activity prevents degradation of a phosphaturic factor. In autosomal
      dominant hypophosphatemic rickets, a mutant form of FGF 23 that is resistant to
      proteolytic degradation causes increased renal phosphate losses and
      hypophosphatemia.

PMID- 12187321
TI  - A family of calcium-permeable channels in the kidney: distinct roles in renal
      calcium handling.
AB  - PURPOSE OF REVIEW: Calcium is an essential intracellular messenger and a major
      component of the mineral phase of the skeleton. Calcium is absorbed in the
      intestine and reabsorbed in the kidney. The underlying transepithelial calcium
      transport mechanisms play crucial roles in calcium homeostasis. In this review,
      we present new developments in the area of calcium transport at the apical
      membrane, the first step in transepithelial calcium transport. RECENT FINDINGS:
      Recently, a group of transient receptor potential (TRP)-related calcium-permeable
      channels has been identified. Several of these channels serve as important
      epithelial calcium entry mechanisms and possibly also as osmolarity sensors.
      SUMMARY: Calcium channels in the kidney play important roles in maintaining total
      body calcium homeostasis. Their dysfunction may be associated with several human
      diseases such as hypercaliuric nephrolithiasis, certain forms of osteoporosis,
      Gitelman's disease and Bartter's syndrome.

PMID- 12187322
TI  - Inherited disorders of the H+-ATPase.
AB  - PURPOSE OF REVIEW: The alpha-intercalated cell in the distal nephron shares a
      number of molecular features with the osteoclast, including site-limited proton
      pumps that are present at high density. These are multisubunit H -ATPases, which
      are essential for acid-base homeostasis and for the maintenance of normal bone
      turnover. In recent years it has become evident that some rare inherited human
      disorders are due to pump dysfunction in kidney or in bone; these are reviewed
      here. RECENT FINDINGS: The present review provides an overview of acid secretion
      in both kidney and bone, and describes the recently identified diseases that are
      associated with mutations in tissue-specific subunits of these pumps. SUMMARY:
      Elucidation of the molecular bases of a number of inherited renal acidopathies
      and bone disorders raises the possibility that additional tissue-specific
      subunits of these important pumps will be identified, gives hope for a better
      understanding of normal function at the molecular level, and may have
      implications for future therapeutic development.

PMID- 12187323
TI  - The clinical development of the bryostatins.
AB  - The bryostatins are a group of novel macrocyclic lactones derived from the marine
      bryozoan, Bugula neritina. In vitro evidence indicates that their main mechanism
      of action is modulation of protein kinase C (PKC) activity. Phase I studies
      suggested significant antineoplastic activity against several tumor types and
      defined the main dose-limiting toxicity as myalgia. Bryostatin-1 has subsequently
      been investigated extensively in phase II clinical trials as a single agent,
      although trial design has been hampered by lack of human pharmacokinetic data.
      Results have been generally disappointing but in vitro and animal data suggests
      an important role for bryostatin-1 in combination with cytotoxic agents.
      Preliminary results of phase I studies support these observations but further
      work needs to be done to define the future role of the bryostatins in the clinic.

PMID- 12187324
TI  - Gemtuzumab Ozogamicin (CMA-676, Mylotarg) for the treatment of CD33+ acute
      myeloid leukemia.
AB  - Gemtuzumab Ozogamicin (GO, CMA-676) is a monoclonal antibody against the cellular
      surface antigen CD33 conjugated with the cytotoxic antibiotic calicheamicin. In
      the beginning of 2000 it obtained US Food and Drug Administration approval for
      the treatment of refractory acute myeloid leukemia (AML) expressing CD33 in
      patients older than 60 years who are not candidates for other chemotherapy. After
      ligation with the CD33 on the cell surface, GO is internalized and hydrolyzed.
      Its two components are released into the cytoplasm and calicheamicin enters the
      nucleus where it associates with the DNA, causing double helix breaks and finally
      cell death. GO is in general well tolerated. The most frequent adverse effect
      observed is myelotoxicity, with prolonged neutropenia and thrombocytopenia. Veno
      occlusive disease of the liver is a less frequent but severe adverse effect. A
      phase II study points towards a percentage of overall hematologic response around
      30% in the setting of refractory or relapsed disease. Future phase III trials
      will show the most suitable place of GO in the treatment of AML.

PMID- 12187325
TI  - Cytokine receptor as a sensitizer for targeted cancer therapy.
AB  - Introducing a cytokine receptor as a sensitizer into cancer cells offers a unique
      opportunity for receptor-targeted cancer therapy. It has been shown that
      transfection of the tumor necrosis factor (TNF) receptor gene in cancer cells or
      exposing cancer cells to certain reagents which increase expression of TNF
      receptors results in enhancement of the cytotoxic effect of TNF. In addition, the
      literature suggests that Fas/CD95-mediated apoptotic tumor cell killing is
      augmented by gene transfer of Fas into cancer cells or treatment of cells with
      agents like cisplatin and interferon (IFN)-gamma. In contrast to these
      approaches, we have discovered a new approach to cancer therapy; wherein
      introduction of a cytokine receptor chain into cancer cells sensitizes them to
      receptor-directed cytotoxins. We have demonstrated that when interleukin (IL)-13
      receptor (IL-13R) alpha2 chain, one of the two known IL-13 binding proteins, is
      introduced into cancer cells that do not express this chain the cells acquire
      extreme sensitivity to a chimeric fusion cytotoxin composed of IL-13 and a
      mutated form of Pseudomonas exotoxin (IL13-PE). Cells that do not express this
      chain or express low levels show limited sensitivity to IL13-PE. Acquisition of
      sensitivity to IL13-PE was observed both in vitro and in vivo when IL-13R alpha2
      transfected human tumor cells were implanted in immunodeficient animals followed
      by systemic or regional IL13-PE therapy. Our third generation experiments suggest
      that this approach is feasible for clinical situations as intratumor
      administration of plasmid carrying the IL-13R alpha2 chain gene sensitized these
      tumors to systemic or regional IL13-PE therapy. This unique approach comprising
      gene transfer of cytokine receptor chain and receptor-targeted cytotoxin
      administration represents a novel strategy for cancer therapy.

PMID- 12187326
TI  - Chemosensitivity of normal human trophoblasts evaluated by a newly developed ATP
      based luminescence assay.
AB  - Trophoblast injury may be one of the possible causes of fetal distress associated
      with chemotherapy administered during pregnancy. The purpose of this study was to
      investigate the ex vivo chemosensitivity of normal trophoblasts (NTB) against
      commonly used antineoplastic agents. Using the newly developed ex vivo ATP-based
      trophoblast assay (ATP-TBA), 31 NTB freshly sampled from human placentas
      (gestational week 7-42) were tested against dactinomycin (Act-D), 5-fluorouracil
      (5-FU), 4-OOH-cyclophosphamide (4-HC), vincristine (VCR) and methotrexate (MTX)
      alone or in combination with calcium folate (LV). All agents were studied at
      concentrations relevant to clinical dosages normally used for chemotherapy of
      solid neoplasms. Of 31 samples studied with the ATP-TBA, 20 (65%) were evaluable.
      VCR, Act-D and 4-HC were the most active drugs with 55, 45 and 45% of samples
      responding ex vivo. Antimetabolites were less active, producing ex vivo response
      rates of 25 (MTX) and 20% (5-FU), respectively. MTX activity was largely
      neutralized by adding LV. The chemosensitivity of NTB showed considerable inter
      individual variations and did not decrease with increasing gestational age. We
      therefore conclude that NTB of any gestational age exhibit considerable ex vivo
      sensitivity against common anticancer agents which is comparable to that observed
      for various solid tumors. The ATP-TBA may be helpful in planning future trials
      with both single agents and drug combinations in order to standardize and
      optimize chemotherapy during pregnancy.

PMID- 12187327
TI  - Simple and efficient liposomal encapsulation of topotecan by ammonium sulfate
      gradient: stability, pharmacokinetic and therapeutic evaluation.
AB  - Topotecan (TPT), a topoisomerase I inhibitor, is presently undergoing clinical
      evaluation worldwide. Previous studies have shown that entrapping TPT within
      multi-lamellar vesicle liposome can stabilize the lactone moiety, which is
      structurally important for biological activity. However, low drug:lipid ratios
      due to the amphipathic character and small entrapment volume in the unilamellar
      vesicle limits the development of pharmaceutically acceptable liposomal
      formulation. With an aim to improve on this drawback, we herein describe a method
      that utilizes the ammonium sulfate gradient to entrap TPT into liposomes. By this
      method, the encapsulation efficiency was over 90% and a drug:lipid molar ratio as
      high as 1:5.4 was reached. In comparison with free drug, liposome-encapsulated
      TPT is more stable in physiological conditions and shows higher in vitro
      cytotoxicity. Because of increased blood circulation time, the initial plasma
      concentration and area under the plasma concentration of liposomal drugs were 14
      and 40 times, respectively, of those of free drug. Furthermore, liposome
      encapsulation enhanced the antitumor activity of TPT in syngeneic murine C-26 and
      human HTB-9 xenograft models in vivo. At a dose of 5 mg/kg, the tumor growth
      delay of liposomal formulation was significantly than that of free TPT. Based on
      these results, we believe that this liposomal TPT formulation is worthy of
      further clinical study.

PMID- 12187328
TI  - Raltitrexed plus oxaliplatin as first-line chemotherapy in metastatic colorectal
      carcinoma: a multicentric phase II trial.
AB  - For advanced colorectal carcinoma, two new drugs, raltitrexed (TOM) and
      oxaliplatin (L-OHP), have recently shown interesting results. Preclinical and
      clinical studies suggest that this combination, because of its favorable toxicity
      profile, high response rate and convenient schedule of administration, can be
      administered successfully in this disease. In our phase II study, 37 non pre
      treated patients with metastatic colorectal carcinoma were treated with TOM (3
      mg/m(2)) and L-OHP (130 mg/m(2)) every 3 weeks. In total, 222 cycles were
      administered; all patients received at least 2 cycles (median 6, range 2-8).
      There were two complete and 14 partial responses for an overall response rate of
      43% (95% CI 27-69%). The median time to response was 2.5 months (range 2-4) and
      the median duration was 10.3 months (range 5-18). Twelve of the 23 (52%) patients
      with symptomatic colorectal cancer were classified as clinical benefit responders
      for at least 4 weeks during the study period. Treatment was well tolerated, and
      both acute, essentially hematologic, and cumulative hepatic and neurologic
      toxicities were manageable and reversible. Response rate and toxic effects
      observed during this study warrant additional studies comparing this TOM-L-OHP
      regimen with CPT-11 and/or capacitebine-containing regimens in metastatic
      colorectal carcinoma.

PMID- 12187329
TI  - Effect of novel modulators of protein kinase C activity upon chemotherapy-induced
      differentiation and apoptosis in myeloid leukemic cells.
AB  - Modulation of protein kinase C (PKC) activity has been demonstrated to either
      prevent or enhance drug-induced apoptosis in various tissue types. We tested four
      novel modulators of PKC activity in comparison to the phorbol ester 12-O
      tetradecanoylphorbol-13-acetate (TPA) for the capability to affect
      differentiation, cell cycle progression and apoptosis in the human myeloid
      leukemia cell lines U937 and HL-60. Farnesyl thiotriazole (FTT) and N-(n-heptyl)
      5-chloro-1-naphthalenesulfonamide (SC-10) are both direct activators of PKC,
      whereas 6-(2-(4-[(4-fluorophe-nyl)phenylmethylene]-1-piperidinyl)ethyl)-7-methyl
      5H-thiazolo[3,2-a]pyrimidin-5-one (R59022) and [3-[2-[4-(bis-(4
      fluorophenyl)methylene]piperidin-1-yl)ethyl]-2,3-dihydro-2-thioxo-4(1H)-quin
      azolinone (R59949) are diacyl glycerol kinase inhibitors that activate PKC by
      enhancing the levels of the endogenous ligand diacyl glycerol. U937 cells
      displayed a slight reduction in the number of cells in G(2)/M cell cycle phase
      after exposure to FTT, SC-10, R59022 and R59949, respectively. In contrast, HL-60
      cells demonstrated a largely unaltered cell cycle distribution. Whereas TPA
      treatment resulted in a strong induction of p21(WAF/CIP1), c-Fos and c-Jun
      levels, neither one of the novel PKC activators altered expression of these
      proteins. Consequently, we tested the ability of the activators to cause membrane
      translocation of PKC. While TPA treatment resulted in translocation of the PKC
      isoforms alpha, delta and epsilon, SC-10 and FTT failed to induce alterations in
      the PKC content of the membrane and cytosolic fractions, respectively. Expression
      of the beta(2)-integrin CD11c that is induced during TPA-mediated differentiation
      remained unaltered after exposure to SC-10 and was partly reduced after treatment
      with FTT. To further investigate the effect of these activators upon apoptosis in
      leukemic cells, HL-60 and U937 cells were treated with 1-beta-D
      arabinofuranosylcytosine (Ara-C) or etoposide (VP-16). Whereas TPA strongly
      reduced apoptosis in Ara-C- or VP-16-treated U937 cells, little if any reduction
      was observed after pretreatment with either FTT, SC-10, R59022 or R59949,
      respectively, in these cells. In contrast, TPA enhanced apoptosis in Ara-C- or VP
      16-treated HL-60 cells. Interestingly, FTT and SC-10 demonstrated a protective
      effect in Ara-C-treated HL-60 cells. Taken together, these data suggest that the
      novel PKC activators FTT, SC-10, R59022 and R59949 exhibit modest biological
      effects upon leukemic blast cells, and are not capable of enhancing the apoptotic
      response of these cells to cytotoxic drugs.

PMID- 12187330
TI  - In vitro activity of the novel cytotoxic agent CHS 828 in childhood acute
      leukemia.
AB  - CHS 828, a pyridyl cyanoguanidine, is a new drug candidate now in phase I/II
      trials, that has shown promising anticancer activity in experimental tumor models
      and primary cultures of cancer cells from patients. In this study the
      fluorometric microculture cytotoxicity assay was used for evaluation of CHS 828
      in primary cell cultures from children with acute leukemia. The activity of and
      interaction with the standard drugs, doxorubicin, melphalan, etoposide and
      cytosine arabinoside (Ara-C), were also assessed. Samples from 65 patients, 42
      with acute lymphocytic leukemia (ALL) and 23 with acute myelocytic leukemia (AML)
      were tested with 72-h continuous drug exposure. There was 50% cell kill at very
      low CHS 828 concentrations; median IC50 was 0.01 microM in ALL and 0.03 in AML
      samples (NS) with large interindividual variability in both groups. ALL samples
      were significantly more sensitive than AML samples to melphalan, doxorubicin and
      etoposide, but not to Ara-C. In AML samples, combinations between CHS 828 and
      each of the four standard drugs resulted in significantly lower cell survival
      than either drug alone. This was also observed in ALL samples, except for Ara-C.
      Using the additive interaction model, CHS 828 showed a synergistic effect with
      melphalan in 67%, doxorubicin in 47%, etoposide in 38% and Ara-C in 14% of AML
      samples. In most ALL samples subadditive effects were found. Further exploration
      of CHS 828 in childhood leukemia is warranted, especially in AML.

PMID- 12187331
TI  - Enhanced suppression of prostate tumor growth by combining C-CAM1 gene therapy
      and angiogenesis inhibitor TNP-470.
AB  - We have previously shown that C-CAM1-based gene therapy effectively suppressed
      prostate tumor growth in nude mice xenograft models. In this study, we examined
      the effects of combining C-CAM1-based therapy and TNP-470, a potent angiogenesis
      inhibitor, on prostate cancer in a xenografted tumor model. The direct cytotoxic
      effects of Ad-C-CAM1 (recombinant adenovirus containing C-CAM1 cDNA) and TNP-470
      on DU145 cells in vitro were determined by microculture tetrazolium assay. The in
      vivo antitumor effects of either agent alone were studied in a DU145 xenografted
      tumor model. Cells were infected with Ad-C-CAM1 or the control virus at
      multiplicities of infection (m.o.i.) of 5 or 10 and then inoculated onto nude
      mice 48 h later. TNP-470 (0, 17 or 35 mg/kg) was given 15, 17 and 19 days after
      inoculation. Combined treatments in vivo were carried out to determine whether
      there were synergistic antitumor effects. Both Ad-C-CAM1 and the control virus
      were minimally toxic to DU145 in vitro. There was evident dose-dependent
      suppression of xenografted tumor growth by either Ad-C-CAM1 or TNP-470. By the
      median-effect analysis, combination of the two agents generated strong
      synergistic antitumor effects as shown by marked tumor suppression as compared to
      either treatment alone. The novel strategy may have clinical implications for the
      treatment of prostate cancer.

PMID- 12187332
TI  - Effects of WR-2721 and cyclophosphamide on the cell cycle phase specificity of
      apoptosis in mouse bone marrow.
AB  - Elucidation of the mechanisms of action of the thiol and alkylating agents on
      normal cells requires the knowledge of their cell cycle phase specificity in
      terms of their ability to induce apoptosis. The effects of S-2-/3
      aminopropylamino/ethyl phosphorothioic acid (WR-2721, Amifostine) and
      cyclophosphamide (CP) on apoptosis and cell cycle progression were assessed in
      the mouse bone marrow. Adult male Swiss mice were treated with WR-2721, at a dose
      of 400 mg/kg body weight, and/or CP, at a dose of 200 mg/kg body weight.
      Application of the laser scanning cytometry APO-BRDU assay, a two-color staining
      method for labeling of DNA breaks and cellular DNA, allowed an identification of
      apoptotic and non-apoptotic cells, and their position with respect to their cell
      cycle phase. Temporary alterations in the number of apoptotic cells and also all
      bone marrow cells, including apoptotic and non-apoptotic ones, were determined
      throughout the 240-h period after treatment of mice with WR-2721 and/or CP. These
      drugs, given alone, affected apoptotic cell death and caused deregulation of the
      cell cycle in the bone marrow. WR-2721, applied 30 min prior to CP
      administration, resulted in a suppressing effect on apoptosis and the cell cycle
      perturbation triggered in normal bone marrow cells by the alkylating drug. The
      patterns of changes in the frequency of apoptotic cells and the number of
      apoptotic and non-apoptotic bone marrow cells, observed in all phases of the cell
      cycle, were dependent on the agent(s) given and the time interval after WR-2721
      and/or CP administration.

PMID- 12187333
TI  - 15-Deoxy-delta12,14-prostaglandin J2 induces apoptosis of a thyroid papillary
      cancer cell line (CG3 cells) through increasing intracellular iron and oxidative
      stress.
AB  - Treatment of carcinoma cell lines with 15-deoxy-delta12,14-prostaglandin J2 (15d
      PGJ2), a natural ligand of the peroxisome proliferator-activated receptor-gamma,
      has been reported to induce apoptosis and/or inhibit proliferation. In this
      study, we investigated the cytotoxic effect and the action mechanisms of 15d-PGJ2
      in a thyroid papillary cancer cell line, CG3. The results indicate that 15d-PGJ2
      caused cytotoxicity and increased the amount of intracellular reactive oxygen
      species (ROS) in these cells. Mitochondrial oxidative phosphorylation inhibitors
      (carbonyl cyanide m-chloro-phenylhydrazone, oligomycin, cyclosporin A and
      rotenone), NADPH oxidase inhibitor (diphenyleneiodonium), xanthine oxidase
      inhibitor (allopurinol) and NO synthase inhibitor (N-monomethyl-L-arginine
      acetate) did not reduce the generation of ROS. However, catalase, N-acetyl
      cysteine and the iron chelator desferri-oxamine decreased the intracellular ROS
      of 15d-PGJ2-treated CG3 cells. Furthermore, 15d-PGJ2 enhanced the accumulation of
      iron in the CG3 cells. These data suggest that 15d-PGJ2 induces the generation of
      ROS by enhancing the accumulation of intracellular iron and that the increased
      oxidative stress may cause apoptosis of CG3 cells.

PMID- 12187334
TI  - Preclinical evaluation of alternative pharmaceutical delivery vehicles for
      paclitaxel.
AB  - New solubilizers, including Sorporol 230, Sorporol 120Ex, Aceporol 345-T,
      Aceporol 460 and Riciporol 335, as potential new delivery vehicles for paclitaxel
      were investigated, since recent studies have shown that the paclitaxel delivery
      vehicle Cremophor EL significantly alters the pharmacokinetics of paclitaxel.
      Cremophor EL and Tween 80 were used as a reference. As in the case of Cremophor
      EL, alteration of blood distribution of paclitaxel occurred in the presence of
      all tested vehicles. Also, no differences in the affinity of paclitaxel for the
      tested solubilizers was found during equilibrium dialysis experiments. The
      different vehicles could be distinguished by a different rate of esterase
      mediated breakdown, which was correlated with the fatty acid content of the
      solubilizers. The activation of the complement cascade was less pronounced for
      all solubilizers, except Riciporol 335, compared to Cremophor EL. The strategies
      presented here provide the possibility to rapidly screen future candidate
      delivery vehicles with optimal characteristics for use as a solubilizer in
      clinical formulations of paclitaxel or other poorly water-soluble drugs.

PMID- 12187335
TI  - Dramatic recovery of paclitaxel-disabling neurosensory toxicity following
      treatment with venlafaxine.
AB  - Venlafaxine is an antidepressant which acts through the inhibition of the
      reuptake of norepinephrine and serotonin. Venlafaxine is active against
      neuropathic and chronic pain. We report the case of a 69-year-old woman who
      presented a paclitaxel-induced neuropathy. She presented paresthesias, pin pricks
      in both hands with functional impairment. Venlafaxine hydrochloride was
      introduced at 37.5 mg twice daily. The patient noticed a dramatic recovery of her
      symptoms within 2 days, with both reduction of the paresthesias and functional
      improvement. This is the first report of efficacious use of venlafaxine for the
      treatment of paclitaxel cumulative neurosensory toxicity.

PMID- 12187336
TI  - Importance of right subcostal incisions in patients undergoing TRAM flap breast
      reconstruction.
AB  - The presence of a preexisting subcostal incision alters the approach to breast
      reconstruction and is thought to predispose to donor site skin complications and
      flap loss. The purpose of this study was to determine whether the presence of a
      subcostal scar affects breast or donor site morbidity adversely after transverse
      rectus abdominis musculocutaneous (TRAM) flap breast reconstruction. Twenty-six
      patients with a right subcostal incision (group A) underwent TRAM flap breast
      reconstruction (13 immediate, 13 delayed). The average age was 51 years, and the
      patients had an average body mass index of 25.3. There were 15 right, 10 left,
      and 1 bilateral reconstruction (4 free flaps, 22 pedicled). Outcome measures were
      compared with 126 age- and risk-matched patients (group B) who underwent TRAM
      flap reconstruction without any preexisting abdominal scar. The average age in
      group B was 46.7 years, and the patients had an average body mass index of 24.8.
      The average length of stay in group A was 5.9 days, compared with 4.8 days in
      group B ( < 0.05). There were no significant differences in breast-related
      complications. Donor site complications were higher in group A, with abdominal
      wall skin necrosis being significantly higher in patients with a subcostal
      incision (25%) compared with those patients without abdominal wall scars (5%; =
      0.02). Multivariate analysis revealed a 6.5-fold increase in donor site
      complications in patients with a subcostal incision and a smoking history ( <
      0.05). When adjusted for radiation treatment, the increased incidence in donor
      site complication rate was only marginally significant ( = 0.08). TRAM flap
      breast reconstruction in patients with preexisting right subcostal scars is
      effective with certain technical modifications; however, there is a slight
      predisposition to increased abdominal wall complications. Smoking influenced
      outcome further in patients with a subcostal incision, stressing the importance
      of proper patient selection.

PMID- 12187337
TI  - Comparison between sonography and mammography for breast cancer diagnosis in
      oriental women after augmentation mammaplasty.
AB  - Augmentation mammaplasty has become more popular in Taiwan. Therefore, clinical
      imaging is necessary to evaluate those patients who develop breast cancers. The
      purpose of this study was to evaluate the detection of breast diseases after
      augmentation mammaplasty by means of mammography and sonography. A retrospective
      follow-up study and analysis of diagnostic methods including mammography,
      sonography, physical examination, and aspiration cytology was conducted on 105
      patients who underwent augmentation mammaplasty at Kaohsiung Medical University
      Hospital between 1989 and 2001. A total of 105 patients were identified in this
      study, and mean follow-up was 4 years. Two tumors from 8 cancer patients were
      visible on standard mammograms, and seven tumors were diagnosed as cancer by
      sonography. One of 15 benign breast tumors was interpreted as a suspected cancer,
      and 7 tumors were interpreted as normal findings on mammograms. Fourteen of 15
      benign breast tumors were diagnosed correctly except for one suspicious case
      examined by sonography. Sonography showed the highest rate of diagnostic accuracy
      (91.3%) and mammograms had the lowest rate (73.9%). The accuracy rate of physical
      examination was 73.9%, and aspiration cytology was 90.0% accurate. This study
      affirms that sonography is a more useful diagnostic tool than mammography in
      Taiwanese women who have undergone augmentation mammaplasty.

PMID- 12187338
TI  - Osteogaleal flaps in pediatric cranioplasty.
AB  - Reconstruction of cranial defects larger than 2 to 3 cm in diameter and frontal
      defects of any size is indicated for mechanical protection and cosmetic reasons.
      The authors used osteogaleal flaps for cranioplasty in 2 pediatric patients with
      the aim of decreasing infection risk and maximizing bone healing. In the first
      patient, bone was harvested from the diploe. Children's cranial bones are thin,
      and in the second patient the authors used full-thickness grafts of adjacent
      bone, splitting this into three pieces to cover the recipient and donor sites.
      The postoperative period was uneventful for both children. Scintigraphic studies
      performed the first week after surgery revealed uptake in the flaps. Computed
      tomography demonstrated rapid bone healing with good contouring. The
      scintigraphic findings and rapid bone healing suggest that the bone component of
      the osteogaleal flap nourishes the graft site with blood from the galea and the
      periosteum. These flaps are an ideal choice for reconstruction of cranial defects
      because of their membranous origin, ease of harvest, applicability to any part of
      the calvarium, and reliable vascularity.

PMID- 12187339
TI  - Free lateral supramalleolar flap transfer as a small, thin flap.
AB  - Lateral supramalleolar flaps were elevated as free flaps and transferred with
      microvascular anastomoses in 3 patients. The peroneal vessels were used for the
      vascular anastomosis. In all patients, the flaps survived completely. The free
      lateral supramalleolar flap is thinner than the peroneal flap and is as thin as
      the radial forearm flap. This flap is useful when thin, small flaps are required,
      and may be a valuable alternative to the radial forearm flap because it
      necessitates less donor site morbidity.

PMID- 12187340
TI  - Donor site morbidity after harvest of free osteofasciocutaneous fibular flaps
      with an extended skin island.
AB  - Since 1993, a total of 41 free osteofasciocutaneous fibular flaps with an
      extended skin island (average dimensions, 16.9 cm long [range, 12-22 cm] x 10.7
      cm wide [range, -16 cm], or 180.8 cm [range, 112-352 cm ]) have been used in by
      the authors in various clinical applications. To evaluate donor site morbidity,
      the 41 patients involved were asked to answer a questionnaire and to present
      themselves for clinical and radiological examination. The subjective findings
      reported by these patients, and the examinations, showed that donor site
      morbidity was moderate. Apart from some occurrence of mild edema and pain, as
      well as modest motor weakness of the great toe, and deficiency of distal nervous
      segments, only 7 patients were found to have a slightly positive anterior drawer
      of the talus (anterior subluxation of the talus), but no instability. In
      conclusion, donor site morbidity after harvest of osteofasciocutaneous fibular
      flaps for different clinical indications, where extended skin islands were
      needed, is moderate.

PMID- 12187341
TI  - Lateral circumflex femoral arterial system and perforators of the anterolateral
      thigh flap: an anatomic study.
AB  - The authors performed an anatomic study on 16 thighs of 11 fresh white cadavers
      at the Ludwig-Maximilian University of Munchen, Germany. They analyzed the
      anatomic pattern and caliber of both the lateral circumflex femoral arterial
      system and the perforators nourishing the anterolateral thigh flap. They found
      regularly a majority of musculocutaneous perforators, mainly in the central third
      of the thigh, arising from the descending branch of the lateral circumflex
      femoral artery. Despite the small number of cadavers, they identified several
      differences in the anatomy of the lateral circumflex femoral arterial system.
      These variabilities, especially regarding the descending branch and its
      perforators, could have clinical importance. They also suggest new dissection
      studies by comparing white and oriental anatomy. Their aim is to establish
      whether any difference in the variability of the lateral circumflex femoral
      arterial system could increase the popularity, currently greater in Eastern
      Europe, of the anterolateral thigh flap.

PMID- 12187342
TI  - Free radial forearm flap with adipofascial tissue extension for reconstruction of
      oral cancer defect.
AB  - The radial forearm flap has been one of the most popular flaps used to
      reconstruct defects after oral cancer ablation. However, it sometimes may not
      provide sufficient soft tissue to obliterate the dead space after tumor excision
      and lymph node dissection, which can result in deep wound infection of the neck
      or even orocervical fistula. The authors modified the radial forearm flap with a
      sheet of adipofascial tissue extension to prevent such postoperative
      complications. From January 1997 to December 2000, 52 patients who underwent
      ablative oral cancer surgery were studied. A total of 29 patients (group I)
      underwent reconstruction with the traditional radial forearm flap
      retrospectively, and 23 patients (group II) underwent reconstruction with the
      radial forearm flap along with a sheet of adipofascial tissue extension. The
      radial forearm flap was designed on the axis of the radial artery, was 8 x 4 to
      12 x 10 cm in size, and was sufficient to resurface the intraoral defect. In
      group II, the radial forearm skin flap along with a sheet of adipofascial tissue
      8 x 8 to 12 x 10 cm was used to obliterate the dead space of the oral floor and
      neck. The donor site of both groups was resurfaced with a split-thickness skin
      graft. In group II, the skin flap of the adipofascial tissue was resutured to its
      original site. Two flaps in group I failed because of arterial occlusion and
      required other skin flaps for reconstruction. Postoperative hematoma, which
      required surgical treatment for drainage, developed in five patients in group I.
      None of the patients in group II had hematoma formation. Nine patients in group I
      had a neck wound infection compared with only 2 patients in group II (a
      significant difference). The average volume of drainage and days of
      hospitalization were similar in both groups. The morbidity of the donor site of
      both groups was not significant. The advantages of this modification include 1)
      suitable soft tissue available for dead space obliteration to decrease the chance
      of postoperative hematoma; 2) the important vessels in the neck can be protected;
      3) there is a decrease in neck wound infections; and 4) donor site morbidity is
      similar to the traditional group.

PMID- 12187343
TI  - Hemodynamic changes of the hand after radial forearm flap harvesting.
AB  - After radial forearm flap harvesting, there is some risk for hand circulatory
      disorders. To reveal the changes in circulatory dynamics in the hand after
      harvesting this flap, the authors compared blood pressure and flow by color
      Doppler ultrasonography in the donor and nondonor hands, and evaluated the long
      term changes in these factors in 40 patients undergoing this operation. Blood
      pressure and flow of the index finger in the donor hands were lower than those in
      the nondonor hands during the first 2 months postoperatively, but they virtually
      returned to the level of those in the nondonor hands within 1 year of the
      operation. These results suggest that after harvesting the radial artery,
      collateral circulation in the hand developed during a short postoperative period.
      Therefore, the authors can predict the long-term safety of forearm flap
      harvesting by evaluating the hemodynamic changes of the digits caused by acute
      occlusion of the radial artery preoperatively, which would reflect the
      hemodynamics at an early postoperative stage.

PMID- 12187344
TI  - Effect of transfection time on the survival of epigastric skin flaps pretreated
      with adenovirus encoding the VEGF gene.
AB  - An experimental study was conducted to investigate the effect of time of
      adenovirus-mediated vascular endothelial growth factor (VEGF) gene therapy on the
      viability of epigastric skin flaps. Eighty-four male Sprague-Dawley rats were
      used. Skin flaps measuring 8 x 8 cm were marked on the ventral abdominal wall.
      The upper border of the flap was 1 cm above the costal margin, and the lower
      border was at the pubis and the inguinal fold. The lateral borders of the flap
      corresponded to the location of the distinct conversion of the thin ventral skin
      to the thick dorsal skin. Seven sites in the predicted area of necrosis on the
      outlined skin flaps were chosen for subdermal injections. All injections were
      administered by an individual who was blinded to the different treatment groups.
      The rats received either saline (control group I, N = 28) or adenovirus encoding
      green fluorescent protein (Ad-GFP; group II, N = 28) or Ad-VEGF (group III, N =
      28). The epigastric island skin flaps based solely on the right inferior
      epigastric vessels were elevated either on the same day of injection (day 0 = 12
      hours after transfection, N = 7) or on day 3 (N = 7), day 7 (N = 7), or day 14 (N
      = 7) after subdermal gene therapy. Flaps were sutured back to their native
      configuration. Flap viability was evaluated on day 7 after surgery. Sections of
      the flaps were examined histologically after undergoing hematoxylin-eosin
      staining. There was a significant reduction in mean percentage of necrotic flap
      area by 56%, 67%, 70%, and 54% in flaps transfected with Ad-VEGF, 12 hours, 3
      days, 7 days, and 14 days before flap elevation, respectively ( < 0.05). There
      was no evidence that the mean percentage of skin necrosis in the Ad-GFP group was
      different than in the control group ( = 0.26). There was evidence of mild
      inflammation in flaps pretreated with Ad-GFP and Ad-VEGF compared with the
      control group. The authors demonstrated that adenovirus-mediated gene therapy of
      the abdominal skin after subdermal injections was technically feasible. This was
      demonstrated by the visualization of GFP expression in control experiments using
      a fluorescence microscope. In this study, adenovirus-mediated VEGF gene therapy
      promoted epigastric flap survival, which was not related to the time of
      transfection. These findings raise the possibility that pretreatment with VEGF
      gene therapy using an adenovirus vector may be applicable in patients at risk for
      plastic surgery.

PMID- 12187345
TI  - Early capillary no-reflow during low-flow reperfusion after hind limb ischemia in
      the rat.
AB  - Reduction of arterial inflow after ischemia (low-flow reperfusion) is associated
      with capillary no-reflow and an increase in flap necrosis. The development of
      these complications may be strongly flow-dependent. The authors wanted to examine
      the difference between normal-flow and low-flow reperfusion by assessing the
      gracilis microcirculation with intravital microscopy after 2 hours of hind limb
      ischemia in the rat. Low-flow reperfusion resulted in capillary no-reflow at an
      earlier stage compared with normal-flow reperfusion. The capillary lumen was not
      visible during ischemia and did not open on reperfusion. The authors observed a
      significant ( <0.05) increase in leukocyte adhesion forces to the postcapillary
      venules at a later stage of low-flow reperfusion compared with normal-flow
      reperfusion. However, neither a significant number of adherent leukocytes to the
      postcapillary venules nor obstruction of capillaries by platelet aggregates could
      be detected during low-flow reperfusion. Infusion of the protease inhibitor FOY
      during low-flow reperfusion did not attenuate capillary no-reflow but did reduce
      leukocyte adhesion forces to the postcapillary venules. Thus, low-flow
      reperfusion leads to early capillary no-reflow, which may be responsible for
      further reperfusion damage and flap failure. The mechanism seems to be
      independent of leukocyte adhesion to the postcapillary venules or platelet
      aggregation. Instead, endothelial cell and/or tissue swelling in combination with
      luminal obstruction and leukocyte plugging may be responsible for the early
      capillary no-reflow phenomenon.

PMID- 12187348
TI  - Gigantomastia induced by bucillamine.
AB  - Drug-induced mammary hyperplasias have been reported as rare complications of D
      penicillamine and Neothetazone. The authors report the first case of bucillamine
      induced giant mammary hyperplasia. Bucillamine is used as an antirheumatic drug
      that is structurally analogous to D-penicillamine. A 25-year-old woman with
      rheumatoid arthritis for the past 5 years started to develop gradual enlargement
      of her breasts 15 months before presentation. She had been on a combined
      treatment of steroid and lobenzarit disodium for the first 3 years, and then
      continued with a combined treatment of steroid and bucillamine for the following
      years until she was found to have pulmonary tuberculosis, at which time the
      steroid was suspended 10 months before she visited the authors' clinic. An almost
      total breast reduction was performed; 5 kg of right breast tissue and 7 kg of
      left breast tissue were excised. Retrospectively, bucillamine was believed to be
      the cause of the giant hypertrophy because of its structural similarity to D
      penicillamine, which was the subject of an abundance of reports of mammary
      hyperplasia.

PMID- 12187347
TI  - Using two flaps to achieve aesthetic autologous breast mound reconstruction.
AB  - Breast mound reconstruction can be a particularly difficult procedure in patients
      who have delayed reconstruction. A technique in which two flaps are used is
      described. The lateral thoracodorsal flap is used to create a breast pocket, and
      the latissimus dorsi flap is used to fill this breast pocket. The advantages of
      the technique are one-stage autologous reconstruction with a skin envelope
      similar in color and texture to the opposite breast. The disadvantages include a
      larger scar.

PMID- 12187346
TI  - Homologous collagen dispersion (dermalogen) as a dermal filler: persistence and
      histology compared with bovine collagen.
AB  - To assess the biological behavior and clinical efficacy of homologous collagen
      dispersion (Dermalogen) in augmenting human dermis, Dermalogen and bovine cross
      linked collagen (Zyplast) were compared in a human postauricular injection model.
      Dermalogen (two sites implanted behind one ear) and Zyplast (two sites behind the
      contralateral ear) were injected into an upper to middermal level in 20 healthy
      adults. Digital photographs of all implant sites were taken over a 12-week period
      after injection. Biopsies of each implant type were taken at 4 and 12 weeks after
      injection. At 12 weeks after injection there was a small but significant
      difference in persistence rates between Dermalogen and Zyplast (4% vs. 2%; =
      0.005). Histologically, Dermalogen was identifiable at 4 weeks after
      implantation, with evidence of neovascularization. Zyplast was identified more
      uniformly than Dermalogen in specimens 12 weeks after implantation, and more
      chronic inflammatory cells and foreign body giant cells were seen in the
      Dermalogen specimen. Clinical persistence and the histological behavior of
      Dermalogen appears to be at least as favorable as Zyplast bovine collagen.
      Dermalogen does not require pretesting and can also be used in the patient
      already sensitized to bovine protein. For these reasons, the authors think
      Dermalogen is a reasonable alternative to bovine collagen for facial soft-tissue
      augmentation.

PMID- 12187350
TI  - Biomechanical failure of metacarpal fracture resorbable plate fixation.
AB  - Metacarpal fractures are a relatively common hand injury that may require
      operative intervention to ensure adequate reduction and stabilization. The use of
      permanent hardware, although acceptable, may lead to complications and an
      increased number of surgical procedures. The use of resorbable hardware such as
      poly-L-lactic acid and polyglycolic acid copolymer plates and screws may
      circumvent some of these complications. In vitro studies have demonstrated that
      the biomechanical characteristics of these resorbable plates may provide the
      rigid fixation necessary to allow for union of metacarpal fractures in vivo.
      However, limited clinical data are available regarding the success of their use
      in this application. The authors present what they believe is the first reported
      case of the failure of a poly-L-lactic acid and polyglycolic acid copolymer
      miniplate after use in the fixation of a metacarpal shaft fracture.

PMID- 12187349
TI  - Retrograde-flow medial plantar island flap reconstruction of distal forefoot,
      toe, and webspace defects.
AB  - Plantar forefoot defects have been reconstructed using a wide variety of
      techniques, including skin grafts, local flaps, and free tissue transfer. The
      distally based, retrograde-flow medial plantar island flap provides coverage with
      durable plantar skin from the nonweight-bearing instep area to reconstruct
      defects at the metatarsal heads. This technique requires careful flap dissection,
      and the anterior reach of the flap is limited by its pedicle length and vascular
      pivot point location. The authors describe two cases using this flap for
      reconstruction of tumor resection defects (5 x 6 cm and 5 x 8 cm) involving the
      distal forefoot, toes, and webspaces. One case required venous supercharging of a
      congested flap with an interpositional vein graft. Technical aspects of the
      design, elevation, and inset of the flap that enhance its versatility and
      reliability are presented. The reverse-flow medial plantar fasciocutaneous island
      flap should be considered an option for forefoot defects that extend anteriorly
      onto the metatarsal heads, including defects involving the toes and webspaces.

PMID- 12187351
TI  - New technique of one-stage reconstruction of a large full-thickness defect in the
      upper lip: bilateral reverse composite nasolabial flap.
AB  - Lips are important features because of their location, function, and aesthetics.
      Reconstruction of the upper lip presents the surgeon with one of the greatest
      challenges. Total upper lip reconstruction is a frequent and demanding procedure,
      and its difficulty is related to the size and the site of the loss of the
      aesthetic subunits such as the Cupid's bow and the philtral columns.

PMID- 12187353
TI  - Transconjunctival upper blepharoplasty: a safe and effective addition to facial
      rejuvenation techniques.

PMID- 12187352
TI  - Triple approach to rhinophyma.
AB  - Rhinophyma is a common condition in the west of Scotland. Various surgical
      approaches have been described, most of which rely heavily on electrocautery,
      heated scalpel, or laser coagulation for hemostasis, resulting in thermal injury
      and substantial risk of scarring. The authors describe their experience with the
      "triple approach" for the surgical treatment of rhinophyma, consisting of
      tangential excision for debulking, the use of scissors for sculpting, and the use
      of mild dermabrasion for final contouring. The use of an alginate hemostatic
      dressing is also described. The triple approach has been used in 6 patients with
      pleasing results.

PMID- 12187354
TI  - Touch of the robot.

PMID- 12187355
TI  - Re: combined microvascular anastomosis.

PMID- 12187356
TI  - Re: confounding conflicts of compounding interest.

PMID- 12187357
TI  - Isolated peripheral nerve injury resulting from a dog bite.

PMID- 12187358
TI  - Bilateral brachial plexus palsy after a prolonged surgical procedure of reduction
      mammaplasty, abdominoplasty, and liposuction.

PMID- 12187359
TI  - Lipoma removal with mini incision.

PMID- 12187360
TI  - Severe pulmonary edema related to dextran 40.

PMID- 12187361
TI  - Surgical correction of microstomia in a patient with scleroderma.

PMID- 12187362
TI  - [A case of identification of cremated bones].

PMID- 12187363
TI  - [Tachykininergic neurotransmission in the central nervous system].
AB  - Tachykinins are widely distributed in mammalian central nervous system and exert
      a variety of actions through individual specific receptors. Neurotransmitter
      functions of substance P (SP), a member of mammalian tachykinins, have been
      firmly established in the spinal cord; SP is highly concentrated in the
      superficial layers of the dorsal horn, is released upon electrical stimulation,
      produces a slow excitatory postsynaptic potential in second-order neurons and is
      inactivated by peptidases. Since SP is contained in unmyelinated primary afferent
      fibers, which mediate nociception, SP is thought to transmit nociceptive
      information and contribute to occurrence of pathological pain states such as
      inflammation and nerve injury. Based on these findings, great effort has been
      devoted to developing NK-1 tachykinin receptor antagonists as a potent
      antinociceptive drug, but up to the present such effective drugs are unavailable.
      Tachykinin receptor antagonists have been also attracting much attention as a
      novel therapeutic drug for anxiety and depression other than pain. The amygdala,
      a key brain structure associated with emotional responses, is thought to be a
      target of tachykinin receptor antagonists for exerting psychopharmacological
      actions. Indeed, tachykinins enhance inhibitory synaptic transmission in the
      basolateral complex of the amygdala. Further study of tachykininergic
      transmission in the central nervous systems will open novel fields for
      pharmacology and therapeutics in neuropsychiatric disorders.

PMID- 12187364
TI  - Assessment of endometrial perfusion with Doppler ultrasound in spontaneous and
      stimulated menstrual cycles.
AB  - OBJECTIVE: Endometrial perfusions were measured by Doppler ultrasound to evaluate
      the influence of spontaneous menstrual cycles and to study the effect of
      clomiphene citrate. METHODS: Flow waveforms in right and left uterine arteries
      were obtained by using transvaginal color Doppler ultrasonography in infertile
      women with 60 spontaneous menstrual cycles and 37 clomiphene citrate stimulated
      cycles from the follicular to the luteal phase. RESULTS: In the spontaneous
      menstrual cycles, the uterine arterial blood flow increased significantly from
      the follicular phase to the day of ovulation and then increased markedly to about
      200 approximately 230% of the follicular phase after the 6th day of ovulation. In
      the clomiphene citrate stimulated cycles, the uterine arterial blood flow did not
      change during the periovulatory period and then increased significantly to about
      180 approximately 220% of the follicular phase after the 6th day of ovulation.
      CONCLUSIONS: In the present study, the clomiphene citrate stimulated cycles
      showed lower endometrial perfusion during the periovulatory period compared with
      those in the spontaneous menstrual cycles. The results suggest that the
      assessment of endometrial perfusion with Doppler ultrasound can be used to reveal
      unexplained infertility problems in induced ovarian cycles.

PMID- 12187365
TI  - Effects of trazodone and imipramine on the biological rhythm: an analysis of
      sleep EEG and body core temperature.
AB  - Depression commonly involves abnormalities of the sleep-wake rhythm, the
      temperature rhythm, and other biological rhythms. The changes of these biological
      rhythms are caused in remission by medications. However, it has yet to be
      clarified whether the biological rhythms are changed as a result of recovery from
      depression or from the direct pharmacological effects of the antidepressants.
      Therefore, we have undertaken a study on the direct effects of the
      antidepressants trazodone and imipramine on the biological rhythms of healthy
      volunteers. The study involved 12 healthy male volunteers (ages 21 approximately
      28 years, mean age 23.9+/-1.7 years) who had given written informed consent.
      Placebo, trazodone, and imipramine were each administered in a single blind
      manner four times a day, during the three-day study period. The total daily
      dosage of trazodone was 100 mg (50 mg in one subject), and of imipramine 40 mg
      (20 mg in one subject). Subjects were submitted to polysomnography (PSG) and body
      core temperature (rectal temperature) measurements during the study period. We
      compared the data concerning the antidepressants to those of the placebo. The
      results show that, with regard to the sleep rhythm, trazodone significantly
      increased slow wave sleep (SWS), but no changes were observed in REM (rapid eye
      movement) sleep. Imipramine significantly decreased REM sleep and prolonged the
      REM cycle. With regard to the temperature rhythm, trazodone showed a tendency to
      advance the appearance time of the minimal temperature. Imipramine significantly
      lowered the maximal temperature and decreased the difference between the maximal
      and the minimal temperature, but no changes in the phases were observed. Neither
      antidepressant had any effect on the temperature cycle. Trazodone and imipramine
      showed different effects on PSG. Furthermore, they had different effects on the
      temperature rhythm. The changes of the sleep-wake rhythm were greater than those
      of the temperature rhythm. Although the two antidepressants had different
      mechanisms of action, it is worthy of note that both directly influenced the
      biological rhythms of healthy volunteers.

PMID- 12187366
TI  - The current perception thresholds in normal pregnancy.
AB  - The purpose of this study was to evaluate a quantitative analysis of the
      nociceptive threshold, using the current perception threshold (CPT), in women
      with normal pregnancies and to assess the relationship between nociceptive
      thresholds and ovarian sex steroids. The subjects consisted of 10 women with
      singleton pregnancies and 14 age-matched healthy female volunteers. The CPTs
      (5,250, and 2,000 Hz) of the dominant ankle section were determined with a
      Neurometer CPT/C (Neurotron, Baltimore, MD). Blood samples were collected after
      these examinations, and the total 17beta-estradiol (E(2)) and progesterone
      concentrations in sera were measured. The present findings clearly indicated that
      the CPTs at 2,000 Hz in women at term in normal pregnancies were significantly
      higher than those in nonpregnant women (p<0.05). At 5 and 250 Hz, there was no
      significant difference between pregnant and nonpregnant women. While there was
      also no significant correlation between CPT and E(2), and progesterone, there was
      significant correlation between CPT and the ratio of 17 beta
      estradiol/progesterone (E(2)/P) at 2,000 Hz (p<0.05, r=0.67). We suggest from
      these data that changes in pressure sensitivity occur at term in pregnancy, and
      that other factors, possibly stimulated by both E(2) and progesterone, may play
      an important role in this change.

PMID- 12187367
TI  - Morphological and histochemical characteristics of mast cells and the content of
      in-tissue histamine in various pathological parathyroids: do mast cells
      participate in hormone secretion in human parathyroids?
AB  - The possibility of the participation of mast cells in human parathyroid hormone
      secretion was studied with regard to the frequency, distribution, and sub-types
      of mast cells and the content of in-tissue histamine, a chemical mediator in mast
      cell granules, in human parathyroids with various pathological conditions. The
      above factors were compared between those of a 'normal' parathyroid group and
      those of 'pathological' parathyroids associated with adenoma and hyperplasia.
      Specimens were scanned for the mean value of the mast cell number per field of
      microscopic view and for the ratio of the mast cell number in glandular
      parenchymal tissue to that in interstitial tissue. The activated state of the
      mast cells was examined through classifying the mast cells into two sub-types,
      mucosal mast cells and connective-tissue mast cells. The high-performance liquid
      chromatography (HPLC) method was used for assay of in-tissue histamine. The
      frequency of mast cells showed no difference between the groups, whereas the
      distribution of mast cells, showed a distinct difference. The occurrence rate of
      mast cells in glandular parenchymal tissue in the 'pathological' group presented
      an increase as compared with that in the 'normal' group. Furthermore, the
      occurrence rate of mucosal mast cells in an activated state also showed an
      increase. This suggests that mast cells are likely to participate in parathyroid
      hormone secretion. The histamine-content in the 'normal' group was significantly
      larger than that in the 'pathological' group, which was a different outcome from
      that observed in mast cells from the results of light microscopy. This may
      require taking into consideration the difference in the histamine content of the
      mast cells themselves between that of mucosal mast cells and connective-tissue
      mast cells.

PMID- 12187368
TI  - Floppy aortic valves without aortic root dilatation: clinical, histologic, and
      ultrastructural studies.
AB  - Gross anatomic, histologic and ultrastructural studies were made on 32 floppy
      aortic valves (FAVs) resected at the time of aortic valvular replacement for
      aortic regurgitation. Patients with the FAVs had relatively long clinical courses
      and had severe aortic regurgitation with mild symptoms of heart failure. The
      sizes of the mechanical valves implanted in the patients with FAVs were not
      large, indicating that the aortic regurgitation in these patients was not
      worsened by dilatation of the aortic ring. Two types of FAVs were recognized
      grossly, according to whether they showed abnormal cuspal thickening or thinning.
      Accumulations of myxoid material in the spongiosa were found in all FAVs,
      regardless of cuspal gross morphology. Histologically, the collagen fibers were
      sparse and irregularly arranged and elastic fibers were disrupted and finely
      granular in the myxomaotus areas of FAVs. Ultrastructurally, the myxomatous
      material consisted of numerous star-shaped proteoglycan granules associated with
      spiraling collagen fibrils and abnormal elastic fibers. Numerous spiraling
      collagen fibrils were observed especially at the border area of myxomatous change
      that extended from the spongiosa into the fibrosa. Abnormal elastic fibers had
      either a granular appearance of their amorphous components without microfibrils,
      or irregularly arranged masses of microfibrils without amorphous components.
      These abnormalities of connective tissue components, resulting from defective
      formation and/or increased degradation were similar to those in floppy mitral
      valves, and were related to the floppiness of cardiac valves.

PMID- 12187369
TI  - Immunohistochemical, biochemical and immunoelectron microscopic analysis of
      antigenic proteins on neuroendocrine cell tumors using monoclonal antibody HISL
      19.
AB  - The monoclonal antibody HISL-19 was originally generated after immunizing BALB/c
      mice with human islet cells. We used this antibody to study a wide variety of
      neuroendocrine (NE) and non-NE tumors by immunohistochemical, immunoelectron
      microscopic, and biochemical (Western blotting) techniques. Of the thyroid
      tumors, HISL-19 specifically immunoreacted with medullary carcinoma of the
      thyroid (MCT); of the pancreatic tumors, it reacted with islet cell tumors such
      as insulinomas and a gastrinoma; of the adrenal tumors, it reacted with
      pheochromocytoma. HISL-19 showed particularly strong immunoreactivity to a gross
      granular material at the perinuclear area in the MCT and malignant
      pheochromocytoma but not in the benign pheochromocytoma, although the latter
      cells showed a faint and homogenous positive reactivity in the cytoplasm. The
      strongly HISL-19-positive material was found to consist of newly synthesized
      antigenic proteins with a molecular weight between 60 and 65 kilodaltons (kDa) by
      Western blotting. Immunoelectron microscopic analysis revealed that this
      antigenic protein was located in the secretory granules that appear markedly in
      malignant endocrine tumors, usually located close to the nucleus. Thus, HISL-19
      is a useful and specific marker for the immunohistochemical diagnosis of NE cell
      tumors. The specific antigenic proteins of HISL-19 were defined in MCT and
      malignant pheochromocytoma. These proteins are speculated to be actively
      synthesized and more highly produced in the secretory granules of malignant
      endocrine tumors than benign ones. Thus, a preoperative immunohistochemical study
      using HISL-19 might be useful for predicting the grade of malignancy of endocrine
      malignant tumors and thus help determine an appropriate operative procedure, in
      addition to being a useful marker of neuroendocrine cell tumors.

PMID- 12187370
TI  - Resting energy expenditure in pregnant Japanese women.
AB  - The subjects were 160 pregnant women with no complications who were examined with
      indirect calorimetry by a single observer; 20 healthy age-matched non-pregnant
      women were used as controls. Assessment was performed 12 hours after oral intake
      of food. Each measurement of resting energy expenditure divided by the body
      surface area was analyzed and compared with that of the controls. In pregnant
      women, the mean resting energy expenditure divided by the body surface area did
      not significantly increase until 32 weeks' gestation. Energy expenditure
      increased significantly by about 300 approximately 600 kJ/m(2) between before 31
      weeks' gestation and the end of pregnancy. Significant changes occurred in the 32
      approximately 35 and 36 approximately 40 weeks' gestational stages (3,790+/
      370,4,110+/-385 kJ/m(2)) (p<0.05). Resting energy expenditure increases at
      conception, and does not increase until 32 weeks' gestation, but increases
      gradually from 32 weeks' gestation to term in normal pregnant women as assessed
      by indirect calorimetry.

PMID- 12187371
TI  - A report of two cases of volar and dorsal fractures of the middle phalanx caused
      by a basketball.
AB  - We present two rare cases of volar and dorsal fractures of the middle phalanx at
      the proximal interphalangeal joint (PIPJ). The first case was a 16-year-old girl.
      She hurt her middle finger while playing basketball. A lateral radiograph
      revealed volar and dorsal fractures of the middle phalanx. She underwent external
      immobilization of the PIPJ in 30 degrees of flexion with a splint for 3 weeks.
      The fractures healed 7 weeks after the injury with neither tenderness nor
      limitation of range of motion. The second case was a 16-year-old boy. He injured
      his index finger while playing basketball, and underwent immobilization of the
      PIPJ for 3 weeks. At 10 weeks after the injury, the dorsal fracture was almost
      healed, but the displacement of the volar fragment had worsened. At a 3-year
      follow-up, the dorsal fragment was healed, but the volar fragment remained in a
      site of nonunion. However, there was neither residual deformity nor restriction
      of movement.

PMID- 12187372
TI  - [The efficacy of donepezil in Alzheimer's disease].
AB  - Several studies have reported the efficacy of donepezil (a cholinesterase
      inhibitor) in patients with Alzheimer's Disease, not only for memory disturbances
      but also for psychotic and behavioral disturbances. We have experienced one such
      case that was a 74-year-old female patient with Alzheimer's Disease. Donepezil
      remarkably improved, for the most part, these symptoms in this case. The scale of
      Mini-Mental State Examination (MMSE) was improved from 21/30 to 26/30, and the
      Alzheimer's Disease Assessment Scale (ADAS) was improved from 21.7/70 to 16.3/70.
      It took about 8 weeks of treatment with donepezil to achieve these results,
      although some adverse effects associated with the use of donepezil were found in
      this case. It became difficult for the nursing staff to give care because of
      hyperactivity and self-assertion.However, the relationship between donepezil and
      these behavioral disturbances was not clear.This case indicates that donepezil
      may exacerbate symptoms in Alzheimer's Disease patients who have psychotic and
      behavioral problems. From a clinical point of view, we concluded that donepezil
      is therapeutically efficacious for Alzheimer's Disease sufferers, but that some
      problems still exist.

PMID- 12187373
TI  - [Treatment of superficial esophageal cancer by argon plasma coagulation].

PMID- 12187374
TI  - [Clinical usefulness of the percutaneous trans esophageal gastro-tubing (PTEG)
      for decompression of the bowels and for transintestinal nutrition].

PMID- 12187375
TI  - [A case of fulminant hepatic failure associated with Hepatitis B viral
      Infection].

PMID- 12187376
TI  - Effectiveness of municipal waste compost and its humic fraction in suppressing
      Pythium ultimum.
AB  - The effect of addition of a municipal solid waste (MSW) compost and its water
      soluble and humic fraction to suppress the effect of Pythium ultimum on pea
      plants was studied and compared with that of a chemical pesticide (metalaxyl).
      The biotic and abiotic characteristics of compost involved in the biocontrol
      effects of these materials were also evaluated. The addition into soil of whole
      composts and their humic fractions reduced the effect of the pathogen on pea
      plants, significantly reducing the number of root lesions and Pythium populations
      and avoiding reductions of plant growth. The greatest pathogen suppression was
      achieved with the chemical pesticide. However, it also caused a significant
      decrease in the number of nontarget bacteria and fungi and on beneficial soil
      microorganisms such as Trichoderma and Pseudomonas. Addition of organic
      amendments increased population size of nontarget and specific biocontrol
      microorganisms. The humic fraction showed similar results to compost. All this
      suggests that metalaxyl has a nonspecific effect, producing adverse effects on
      aspects of soil quality. This was avoided if the chemical pesticide was reduced
      and replaced by organic amendments such as an MSW compost or its humic fraction.

PMID- 12187378
TI  - Independent integration of rodent identifier (ID) elements into orthologous sites
      of some RT6 alleles of Rattus norvegicus and Rattus rattus.
AB  - The two alleles of the rat T-cell differentiation alloantigen RT6 are highly
      divergent and their expression is distinctively regulated. While the majority of
      T cells of RT6a/RT6b heterozygous laboratory rats (Rattus norvegicus) expresses
      both alleles, a subpopulation expresses only RT6b. To identify cis-regulatory
      elements that potentially control monoallelic expression, we compared the
      sequences of both alleles. A striking difference is the presence or absence of a
      rodent identifier (ID) sequence in intron 7. All investigated inbred RT6a rat
      strains (n=7) had this integration, while it was absent in all investigated RT6b
      rats (n=9). An ID element was also identified at precisely the same integration
      site in one RT6 allele of the closely related species Rattus rattus. The ID
      elements of both species showed nucleotide substitutions characteristic of
      different subfamilies, and their flanking repeats differed in length, indicating
      that two independent integration events had occurred into the same site adjacent
      to a mammalianwide interspersed repeat. Analysis of the surrounding sequences did
      not disclose any motifs to explain preferential integration into one allele. Our
      data indicate that the RT6 alleles diverged about 1 myr ago and that the ID
      element integrated into the RT6a locus soon after this. We have previously shown
      that DNA methylation plays an important role in regulating monoallelic RT6
      expression. The possibility that the ID element in the RT6a allele interferes
      with the required demethylation process and thus accounts for monoallelic
      expression is discussed.

PMID- 12187377
TI  - Enhanced phosphate uptake and polyphosphate accumulation in Burkholderia cepacia
      grown under low pH conditions.
AB  - Of bacterial cells in a sample of activated sludge, 34% contained detectable
      intracellular polyphosphate inclusions following Neisser staining, when grown on
      glucose/mineral salts medium at pH 5.5; at pH 7.5 only 7% of cells visibly
      accumulated polyphosphate. In a sludge isolate of Burkholderia cepacia chosen for
      further study, maximal removal of phosphate and accumulation of polyphosphate
      occurred at pH 5.5; levels were up to 220% and 330% higher, respectively, than in
      cells grown at pH 7.5. During the early stationary phase of growth at pH 5.5 a
      maximum level of intracellular polyphosphate that comprised 13.6% of cellular dry
      weight was reached. Polyphosphate kinase activity was detected in actively
      growing cells only when cultured at pH 5.5. The phenomenon of acid-stimulated
      phosphate uptake and polyphosphate accumulation in this environmental bacterial
      population parallels observations previously made by us in the yeast Candida
      humicola and may thus represent a widespread microbial response to low external
      pH values.

PMID- 12187379
TI  - Aerobiosis increases the genomic guanine plus cytosine content (GC%) in
      prokaryotes.
AB  - The huge variation in the genomic guanine plus cytosine content (GC%) among
      prokaryotes has been explained by two mutually exclusive hypotheses, namely,
      selectionist and neutralist. The former proposals have in common the assumption
      that this feature is a form of adaptation to some ecological or physiological
      condition. On the other hand, the neutralist interpretation states that the
      variations are due only to different mutational biases. Since all of the traits
      that have been proposed by the selectionists either appeared to be limited to
      certain genera or were invalidated by the availability of more data, they cannot
      be considered as a selective force influencing the genomic GC% across all
      prokaryotes. In this report we show that aerobic prokaryotes display a
      significant increment in genomic GC% in relation to anaerobic ones. This is the
      first time that a link between a metabolic character and GC% has been found,
      independently of phylogenetic relationships and with a statistically significant
      amount of data.

PMID- 12187380
TI  - Divergent intron conservation in the mitochondrial nad2 gene: signatures for the
      three bryophyte classes (mosses, liverworts, and hornworts) and the lycophytes.
AB  - The slow-evolving mitochondrial DNAs of plants have potentially conserved
      information on the phylogenetic branching of the earliest land plants. We present
      the nad2 gene structures in hornworts and liverworts and in the presumptive
      earliest-branching vascular land plant clade, the Lycopodiopsida. Taken together
      with the recently obtained nad2 data for mosses, each class of bryophytes
      presents another pattern of angiosperm-type introns conserved in nad2: intron
      nad2i1 in mosses; intron nad2i3 in liverworts; and both introns, nad2i3 and
      nad2i4, in hornworts. The lycopods Isoetes and Lycopodium show diverging intron
      conservation and feature a unique novel intron, termed nad2i3b. Hence,
      mitochondrial introns in general are positionally stable in the bryophytes and
      provide significant intraclade phylogenetic information, but the nad2 introns, in
      particular, cannot resolve the interclade relationships of the bryophyte classes
      and to the tracheophytes. The necessity for RNA editing to reconstitute conserved
      codon entities in nad2 is obvious for all clades except the marchantiid
      liverworts. Finally, we find that particularly small group II introns appear as a
      general feature of the Isoetes chondriome. Plant mitochondrial peculiarities such
      as RNA editing frequency, U-to-C type of RNA editing, and small group II introns
      appear to be genus-specific rather than gene-specific features.

PMID- 12187381
TI  - Molecular and evolutionary analysis of mussel histone genes (Mytilus spp.):
      possible evidence of an "orphon origin" for H1 histone genes.
AB  - Linker histones are a divergent group of histone proteins with an independent
      evolutionary history in which, besides somatic subtypes, tissue- and
      differentiation-specific subtypes are included. In the present work H1 histone
      coding and noncoding segments from five Mytilus mussel species (Mollusca:
      Bivalvia) widely distributed throughout the world have been determined and
      characterized. Analysis of promoter regions shows clear homologies among Mytilus
      H1 genes, sea urchin H1 genes, and vertebrate differentiation-specific H1
      subtypes (H5 and H1(o)), all having an H4 box motif in common. The amino acid
      sequence of the H1 protein central conserved domain is also closely related to
      that previously defined for the vertebrate divergent subtypes. A phylogenetic
      tree reconstructed from different H1 genes from several species strengthens the
      hypothesis of an "orphon" origin for the Mytilus H1 genes, as well as for the
      H1(o)/H5 genes from vertebrates and the H1D gene from the sea urchin
      Strongylocentrotus purpuratus, is suggested. As additional data, the average copy
      number of the H1 genes in the species analyzed was estimated as being 100 to 110
      copies per haploid genome, where FISH revealed telomeric chromosomal location for
      several H1 copies in M. galloprovincialis. The contribution of such proximity to
      heterochromatic regions over the amount of codon bias detected for H1 genes is
      discussed.

PMID- 12187382
TI  - Intra- and interfamily relationships of Vespertilionidae inferred by various
      molecular markers including SINE insertion data.
AB  - The family Vespertilionidae comprises the largest number of species in the order
      Chiroptera, and its members are distributed over most of the world. We collected
      sequences of the mitochondrial NDI (NADH dehydrogenase subunit 1) gene from 38
      species as well as 20 sequences of exon28 of the vWF (von Willebrand Factor) gene
      and analyzed phylogenetic relationships in Vespertilionidae using maximum
      likelihood analyses and SINE (short interspersed elements) insertions. Our data
      strongly suggest the following: (1) Murininae and Myotis, each of which is
      classified into different subfamilies, are monophyletic; (2) the monophyly of
      Murininae, Myotis, Pipistrellini, and Plecotini is supported by our analyses of
      the NDI and nuclear vWF as well as data from SINE insertions, while Miniopterinae
      was not included in this group; and (3) Rhinolophoidea (microchiroptera) is
      separated from all the other microchiropteran species. Our study represents the
      most comprehensive phylogenetic model of Vespertilionidae to date.

PMID- 12187383
TI  - Characterization of the I-Spom I endonuclease from fission yeast: insights into
      the evolution of a group I intron-encoded homing endonuclease.
AB  - The first group I intron in the cox1 gene (cox1I1b ) of the mitochondrial genome
      of the fission yeast Schizosaccharomyces pombe is a mobile DNA element. The
      mobility is dependent on an endonuclease protein that is encoded by an intronic
      open reading frame (ORF). The intron-encoded endonuclease is a typical member of
      the LAGLIDADG protein family of endonucleases with two consensus motifs. In
      addition to this, analysis of several intron mutants revealed that this protein
      is required for intron splicing. However, this protein is one of the few group I
      intron-encoded proteins that functions in RNA splicing simultaneously with its
      DNA endonuclease activity. We report here on the biochemical characterization of
      the endonuclease activity of this protein artificially expressed in Escherichia
      coli. Although the intronic ORF is expressed as a fusion protein with the
      upstream exon in vivo, the experiments showed that a truncated translation
      product consisting of the C-terminal 304 codons of the cox1I1b ORF restricted to
      loop 8 of the intron RNA secondary structure is sufficient for the specific
      endonuclease activity in vitro. Based on the results, we speculate on the
      evolution of site-specific homing endonucleases encoded by group I introns in
      eukaryotes.

PMID- 12187384
TI  - Phylogenetic analysis shows that the OXA beta-lactamase genes have been on
      plasmids for millions of years.
AB  - The OXA genes encode a class of beta-lactamases that confer resistance to a wide
      range of beta-lactam antibiotics. To determine whether the diversity of the OXA
      beta-lactamases is the result of recent or ancient events, and to determine
      whether mobilization of the OXA genes from chromosomes to plasmids occurred
      recently or long ago, we have constructed a Bayesian phylogeny of the OXA beta
      lactamase genes. Analysis of that phylogeny shows that much of the diversity is
      the result of ancient events and that the OXA genes were mobilized from
      chromosomes to plasmids on at least two independent occasions that occurred
      millions of years ago. That observation contradicts the commonly held impression
      that mobilization of antibiotic resistance genes is strictly the result of modern
      use of antibiotics.

PMID- 12187385
TI  - JC virus strains indigenous to northeastern Siberians and Canadian Inuits are
      unique but evolutionally related to those distributed throughout Europe and
      Mediterranean areas.
AB  - Human polyomavirus JC virus (JCV) isolates around the world are classified into
      more than 10 geographically distinct genotypes (designated as subtypes).
      Evolutionary relationships among JCV subtypes were recently examined, and the
      following pattern of JCV evolution was indicated. The ancestral JCV first divided
      into three superclusters, designated Types A, B, and C. A split in Type A
      generated two subtypes, EU-a and -b, containing mainly European and Mediterranean
      isolates. The split in Type B generated Af 2 (the major African subtype), Bl-c (a
      minor European subtype), and various Asian subtypes. Type C generated a single
      subtype (Afl), consisting of isolates derived from western Africa. In this study,
      JCV isolates prevalent among northeastern Siberians and Canadian Inuits were
      evaluated in the context of the above-described pattern of JCV evolution. The
      Siberian/Arctic JCV isolates were classified as belonging mainly to Type A, based
      on the result of a preliminary phylogenetic analysis. We then examined, using the
      whole-genome approach, the phylogenetic relationships among worldwide Type A
      isolates. In neighbor-joining and maximum-likelihood analyses, Type A JCVs
      worldwide consistently diverged into three subtypes, EU-a, -b, and -c, with high
      bootstrap probabilities. EU-c was constructed only by northeastern Siberian
      isolates, derived mainly from Nanais living in the lower Amur River region, and
      was shown to have been generated by the first split in Type A. Most
      Siberian/Arctic isolates derived from Chukchis, Koryaks, and Canadian Inuits
      formed a distinct cluster within the EU-a subtype, with a high bootstrap
      probability. Based on the present findings, we discuss ancient human migrations,
      accompanied by Type A JCVs, across Asia and to Arctic areas of North America.

PMID- 12187386
TI  - Identification and phylogenetic analysis of a glucose transporter gene family
      from the human pathogenic yeast Candida albicans.
AB  - We have identified a large family of glucose transporter genes (HGT1 to HGT20)
      from the human pathogenic yeast Candida albicans by screening of genomic
      sequences, reverse-transcription PCR assays, and phylogenetic analyses. The
      putative glucose transporter ORF sequences share among themselves 10-93% pairwise
      sequence identity and, in comparative analyses of predicted amino acid sequences,
      exhibit similarities to human and yeast transporters of the major facilitator
      superfamily (MFS): the predicted 12-transmembrane domains and sugar transporter
      signatures align closely to those of HXT transporters of Saccharomyces cerevisiae
      and GLUT transporters of humans, with amino acid residues at certain positions
      highly conserved throughout the families. Reverse-transcription PCR analyses
      demonstrated that the majority of the glucose transporters was transcribed in
      culture medium containing 2% glucose, while several were transcribed in the
      presence of low (0.2%) and/or high (5%) concentrations of glucose. Phylogenetic
      analyses revealed that there were three distinct clades of 20 HGT genes, which
      might represent three possible subfamilies. Additionally, HGT18 and HGT20 show a
      high overall sequence identity to the human GLUTs, indicating a possible
      functional convergence. We conclude that glucose transporters in C. albicans
      comprise a family of 20 known members, with variable transcription in response to
      glucose concentration.

PMID- 12187387
TI  - When comparative information leads us astray: the receptor-binding region of
      colicin E9.
AB  - In an effort to develop derivatives of the Escherichia coli antimicrobial protein
      colicin E9 that exhibit novel interactions with a target cell, we mutagenized a
      10-amino acid region located at the C terminus of the colicin receptor-binding
      domain. We subsequently selected for those colicin molecules that retain the
      antimicrobial phenotype and found that, despite a mutagenic strategy that alters
      every amino acid in the targeted domain, more than 70% of the engineered colicins
      retained antimicrobial activity. This result is all the more surprising given the
      extensive phylogenetic conservation of this receptor-binding domain, which
      originally suggested the operation of strong selective constraints on the amino
      acid sequence of this region. This apparent contradiction between our
      experimental results and the comparative data is resolved by exploring the
      fitness consequences of the experimentally induced amino acid substitutions. In
      17 of 52 cases we examined, the fitness of cells harboring the functional
      engineered colicins was lower than that of our control line (containing wild-type
      colicin E9), and in 33 of 52 cases, equal to it. Paradoxically, two of the
      engineered colicins appear to confer a higher fitness to the producer cell lines.
      While the mechanism linking changes in the amino acid sequence of the colicin
      receptor-binding domain and the growth rate of the cells remains unclear, these
      results illustrate the surprising versatility of the colicin/receptor interaction
      and underscore the importance of distinguishing molecular function from
      organismal fitness.

PMID- 12187388
TI  - Analysis of the phylogenetic distribution of isochores in vertebrates and a test
      of the thermal stability hypothesis.
AB  - Warm-blooded vertebrates show large-scale variation in G + C content along their
      chromosomes, a pattern which appears to be largely absent from cold-blooded
      vertebrates. However, compositional variation in poikilotherms has generally been
      studied by ultracentrifugation rather than sequence analysis. In this paper, we
      investigate the compositional properties of coding sequences from a broad range
      of vertebrate poikilotherms using DNA sequence analysis. We find that on average
      poikilotherms have lower third-codon position GC contents (GC3) than homeotherms
      but that some poikilotherms have higher mean GC3 values. We find that most
      poikilotherms have lower variation in GC3 than homeotherms but that there is a
      correlation between GC12 and GC3 for some species, indicating that there is
      systematic variation in base composition across their genomes. We also
      demonstrate that the GC3 of genes in the zebrafish, Danio rerio, is correlated
      with that in humans, suggesting that vertebrates share a basic isochore
      structure. However, we find no correlation between either the mean GC3 or the
      standard deviation in GC3 and body temperature.

PMID- 12187389
TI  - Molecular phylogeny of the extinct pleistocene dwarf elephant Palaeoloxodon
      antiquus falconeri from Tilos Island, Dodekanisa, Greece.
AB  - A partial sequence of cytochrome b (228 bp) gene of mitochondrial DNA was
      successfully determined from rib bones of the dwarf elephant Palaeoloxodon
      antiquus falconeri BUSK, which were excavated from Charkadio cave of the island
      of Tilos, Dodekanisa, Greece. This is the first report of DNA sequence of a dwarf
      elephant. The sequences were used to examine the phylogenetic relationships among
      Elephantidae. Phylogenetic trees reconstructed by the neighbor-joining and
      maximum parsimony methods provided identical topologies. The results support the
      "Palaeoloxodon-Elephas" clade, which is consistent with previous morphological
      reports according to which Palaeoloxodon is more closely related to Elephas than
      to Loxodonta or Mammuthus.

PMID- 12187390
TI  - High-density lipoprotein apolipoprotein A-I kinetics in obese insulin resistant
      patients. An in vivo stable isotope study.
AB  - AIMS/HYPOTHESIS: Mechanisms responsible for the decreased high-density
      lipoprotein (HDL) cholesterol level associated with insulin resistance in obese
      patients are not clearly understood. To determine the influence of insulin
      resistance at an early stage on HDL metabolism, we performed a stable isotope
      kinetic study of apolipoprotein (apo) A-I, in five obese insulin resistant women
      with normal fasting triglycerides and without impaired glucose tolerance, and in
      five age-matched control women. METHODS: Each subject received a 16 h constant
      infusion of L-[1-(13)C]leucine at 0.7 mg/kg/h following a primed bolus of 0.7
      mg/kg. RESULTS: ApoA-I fractional catabolic rate (FCR) was significantly
      increased in insulin-resistant women compared to controls (0.316+/-0.056 vs
      0.210+/-0.040 per day, P<0.01), indicating a significant 50% increase of apoA-I
      catabolism, leading to an important reduction of plasma apoA-I residence time
      (3.25+/-0.59 vs 4.92+/-1.11, P<0.01). ApoA-I production rate tended to be higher
      in insulin resistant women than in controls (364+/-77 vs 258+/-60 mg/l/day,
      P=0.13), but the difference was not statistically significant. ApoA-I FCR was
      correlated with triglycerides during the fed state (r=0.69; P=0.026) and HDL
      triglycerides-esterified cholesterol ratio (r=0.73; P=0.016), suggesting that
      alteration of apoA-I metabolism in insulin resistance may be partly related to
      HDL enrichment in triglycerides. CONCLUSIONS: Our kinetic study shows that
      patients, at an early stage of insulin resistance (without impaired glucose
      tolerance nor fasting hypertriglyceridaemia), already have a significant
      alteration of apoA-I metabolism (increased apoA-I catabolism), which is
      consistent with the increased risk of atherosclerosis in this population.

PMID- 12187392
TI  - Skeletal muscle triglycerides lowering is associated with net improvement of
      insulin sensitivity, TNF-alpha reduction and GLUT4 expression enhancement.
AB  - AIMS/HYPOTHESIS: The aim of the present study was to investigate the relationship
      between intramyocytic triglycerides levels, muscle TNF-alpha and GLUT4 expression
      and insulin resistance. METHODS: Insulin sensitivity was studied in 14 severely
      obese women (BMI>40 kg/m(2)), before and 6 months after low-dietary intake or
      bariatric malabsorptive surgery (bilio-pancreatic diversion, BPD), by the
      euglycaemic hyperinsulinaemic clamp technique, while the amount of intramyocytic
      triglycerides was chemically measured in needle muscle biopsies. Using reverse
      transcriptase-polymerase chain reaction analysis, the muscle mRNA expression of
      TNF-alpha and GLUT4 was also investigated. RESULTS: The weight loss after surgery
      was 25.98+/-5.81 kg (P<0.001), while that obtained with the diet was 5.07+/-5.99
      kg (P=NS). Marked decrease in TNF-alpha mRNA levels (76.67+/-12.59 to 14.01+/
      5.21 AU, P<0.001) were observed in comparison with pre-treatment, whereas GLUT4
      was significantly increased (62.25+/-11.77-124.25+/-21.01 AU, P<0.001) only in
      BPD patients. Increased glucose uptake (M) was accompanied by a significant
      decrease of TNF-alpha mRNA (76.67+/-12.59-14.01+/-5.21 AU, P<0.01) and an
      increase of GLUT4. The amounts of TNF-alpha mRNAs in skeletal muscle correlated
      inversely with GLUT4 mRNAs and directly with intramyocytic triglycerides levels.
      In a step-down regression analysis (r(2)=0.95) TNFalpha mRNA (P=0.0014), muscular
      TG levels (P=0.018), and GLUT4 mRNA (P=0.028) resulted to be the most powerful
      independent variables for predicting M values. CONCLUSION/INTERPRETATION: These
      findings suggest that insulin resistance in morbidly obese patients is positively
      associated to the intramyocytic triglycerides content and to TNF-alpha gene
      expression and inversely correlated to GLUT4 expression.

PMID- 12187391
TI  - Obesity is an independent risk factor for plasma lipid peroxidation and depletion
      of erythrocyte cytoprotectic enzymes in humans.
AB  - OBJECTIVE: Obesity, defined as a body mass index (BMI) greater than 30 kg/m(2),
      is now recognised as a risk factor for diabetes mellitus, hyperlipidaemia, colon
      cancer, sudden death and other cardiovascular diseases. In this study, it is
      hypothesized that obesity is an independent risk factor for lipid peroxidation
      and decreased activities of cytoprotective enzymes in humans. SUBJECTS: Fifty
      normal healthy subjects with healthy BMI (19-25 kg/m(2)) and 250 subjects with
      different grades of obesity (30-50 kg/m(2)) with no history of smoking or
      biochemical evidence of diabetes mellitus, hypertension, hyperlipidaemia, renal
      or liver disease or cancer. MEASUREMENTS: To test this hypothesis, we assessed
      lipid peroxidation and cytoprotection by measuring the concentrations of plasma
      malondialdehyde (P-MDA) and the activities of erythrocyte copper zinc-superoxide
      dismutase (CuZn-SOD) and glutathione peroxidase (GPX). RESULTS: The concentration
      of P-MDA was significantly lower (P<0.001) in subjects with healthy BMI (2.53+/
      0.04 micro mol/l) than in those with BMI above 40 kg/m(2) (4.75+0.05 micro
      mol/l). Furthermore, there was a significantly positive association (r=0.342,
      P=0.013) between BMI and P-MDA. On the other hand, subjects with healthy BMI had
      significantly higher (P<0.001) erythrocyte CUZn-SOD (1464+/-23 units/g Hb) and
      GPX (98.4+/-3.3 units/g Hb) than those with BMI above 40 kg/m(2) (1005+/-26
      units/g Hb) and (84.3+/-6.7 units/g Hb) respectively. Furthermore, erythrocyte
      CuZn-SOD and GPX activities were negatively associated with BMI (r=-0.566,
      P=0.005 and r=-0.436, P=0.018) respectively. CONCLUSION: It is concluded from
      these results that obesity in the absence of smoking, diabetes mellitus,
      hyperlipidaemia, renal or liver disease causes lipid peroxidation and decreased
      activities of cytoprotective enzymes, and should therefore receive the same
      attention as obesity with complications.

PMID- 12187393
TI  - Body weight changes and the A-6G polymorphism of the angiotensinogen gene.
AB  - BACKGROUND: The objective of the study was to analyze the relationship of
      polymorphisms of the angiotensinogen gene with changes in body weight during 3 y
      of antihypertensive treatment, in a group of young adults with essential
      hypertension. METHODS: Essential hypertensives, less than 50 y old, never
      previously treated with antihypertensive drugs and in the absence of diabetes
      mellitus were included. After the initial evaluation, patients were treated using
      only non-pharmacological measures (n=29), beta-blockers (n=40) or angiotensin
      converting enzyme inhibitors (n=66). Resting blood pressure, biochemical profile
      and body weight at the beginning and yearly were measured. The polymorphism A-6G
      of the angiotensinogen gene located in the promoter region was analyzed. RESULTS:
      One-hundred and thirty-five patients were included. Genotypes of the A-6G
      polymorphism of the AGT gene were in Hardy-Weinberg equilibrium (AA 34, AG 63, GG
      38). No significant differences were observed among genotypes in terms of age,
      body mass index, body weight, systolic or diastolic blood pressure. No
      significant differences in the genotype distribution or in the allele frequencies
      were observed, although the A allele was most frequent among the obese subjects.
      During the 3 y of antihypertensive treatment, there was a trend to increase
      weight despite the dietary recommendations. The slopes of body weight over time,
      adjusted by age and baseline BMI, differed significantly among the homozygote
      genotypes (P=0.006). The highest were for those with the AA genotype and the
      lowest for the GG genotype (1.180+/-0.25 and -0.128+/-0.24 kg/y; P=0.0001). The
      influence of the genotype in the changes on body weight remained significant
      after considering its interaction with the kind of antihypertensive treatment,
      although among subjects carrying the AA genotype those treated with ACEi showed
      the least body weight change. Furthermore, A-6G genotypes had the largest
      influence on weight changes, accounting for 19% of the variance, when age, sex
      and initial body mass index were included in the model. CONCLUSIONS: In a group
      of young adult hypertensive subjects, there was a trend to increase weight
      despite dietary recommendations. Subjects with the AA genotype were those with
      the largest weight gain, but this effect was modified by the antihypertensive
      treatment.

PMID- 12187394
TI  - Association analysis of genes involved in the leptin-signaling pathway with
      obesity in Brazil.
AB  - OBJECTIVE: To investigate associations of polymorphisms in the LEP, LEPR and NPY
      genes with obesity-related traits in a Brazilian population of European descent.
      METHODS: A total of 183 women and 153 men (mean body mass index (BMI), 26.1+/-4.8
      kg/m(2)) were genotyped using the PCR-RFLP procedure for the LEP A19G, LEPR
      Gln223Arg, LEPR PRO1019pro and NPY Leu7Pro polymorphisms. Frequencies were
      compared among normal-weight and overweight plus obese groups with chi-square
      tests, mean BMI and waist circumference were compared among genotypes by t-tests
      and analysis of variance. RESULTS: The genotype and allele frequencies of the
      LEPR Gln223Arg polymorphism were significantly different between normal-weight
      and overweight plus obese groups (P=0.013 and 0.009, respectively). Although
      there was no difference in the mean adjusted BMI among the three LEPRGln223Arg
      genotypes, a trend was observed for Arg/Arg individuals to have a higher mean BMI
      compared to Gln/Gln homozygotes, with heterozygote individuals presenting
      intermediate mean BMI between the two homozygote groups (ANOVA, P=0.063).
      However, in non-smokers, the LEPR Gln223Arg polymorphism showed a highly
      significant effect over BMI (P=0.009). When the analysis was restricted to
      premenopausal women, a highly significant effect of NPY was observed. Women
      bearing the Pro variant presented a lower BMI than wild-type homozygotes
      (P=0.001). CONCLUSION: Our findings suggest that genetic variability in the
      leptin receptor and neuropeptide Y genes is implicated in body weight regulation,
      the LEPR Gln223Arg variant being associated with a BMI increase in this Caucasian
      population, especially in non-smokers, while the NPY Leu7Pro polymorphism was
      associated with BMI reduction in premenopausal women.

PMID- 12187395
TI  - Obesigenic families: parents' physical activity and dietary intake patterns
      predict girls' risk of overweight.
AB  - OBJECTIVE: To determine whether obesigenic families can be identified based on
      mothers' and fathers' dietary and activity patterns. METHODS: A total of 197
      girls and their parents were assessed when girls were 5 y old; 192 families were
      reassessed when girls were 7 y old. Measures of parents' physical activity and
      dietary intake were obtained and entered into a cluster analysis to assess
      whether distinct family clusters could be identified. Girls' skinfold thickness
      and body mass index (BMI) were also assessed and were used to examine the
      predictive validity of the clusters. RESULTS: Obesigenic and a non-obesigenic
      family clusters were identified. Mothers and fathers in the obesigenic cluster
      reported high levels of dietary intake and low levels of physical activity, while
      mothers and fathers in the non-obesigenic cluster reported low levels of dietary
      intake and high levels of activity. Girls from families in the obesigenic cluster
      had significantly higher BMI and skinfold thickness values at age 7 and showed
      significantly greater increases in BMI and skinfold thickness from ages 5 to 7 y
      than girls from non-obesigenic families; differences were reduced but not
      eliminated after controlling for parents' BMI. CONCLUSIONS: Obesigenic families,
      defined in terms of parents' activity and dietary patterns, can be used predict
      children's risk of obesity.

PMID- 12187396
TI  - Weight-loss attempts and reporting of foods and nutrients, and biomarkers in a
      national cohort.
AB  - OBJECTIVE: This study examined the reported intake of foods and nutrients, and
      biomarkers of dietary exposure and cardiovascular disease in relation to history
      of trying to lose weight. METHODS: Dietary, anthropometric and biochemical data
      were from the third National Health and Nutrition Examination Survey (1988-1994),
      n=13 092. The history of attempting weight loss variable was created as follows:
      trying to lose currently and tried in the past 12 months (Y/Y); trying to lose
      currently, but not tried in the past 12 months (Y/N), not trying currently, but
      tried in the past 12 months (N/Y); not trying now and not tried in the past 12
      months (N/N). Multiple regression methods were used to examine the independent
      association of history of trying to lose weight with reported intakes of energy,
      nutrients, percentage energy from low-nutrient-dense foods (sweeteners, baked and
      dairy desserts, visible fats and salty snacks), and serum concentrations of
      vitamins, carotenoids and lipids. RESULTS: Men and women in the Y/Y group
      reported lower energy intake relative to the N/N group (P<0.0000). However, the
      reported percentage energy from fat and carbohydrate by the Y/Y group did not
      differ from the N/N group. Percentage of energy from low-nutrient-dense foods was
      lower in men in the Y/Y group but not women. The relative odds of reporting the
      estimated average requirement (EAR) of folate, and vitamins A, B(6), B(12), C, E
      and iron and adequate intake (AI) of calcium were not adversely affected by
      history of trying to lose weight in men. In women, the odds of meeting the folate
      and vitamin E EAR were lower in the Y/Y group. Some history of weight loss
      categories were significant positive predictors of serum vitamin and carotenoid
      concentrations, or unrelated to cardiovascular disease risk biomarkers.
      CONCLUSIONS: There was little evidence for increased nutritional risk in those
      reporting repeat attempts at weight loss.

PMID- 12187397
TI  - The relation of gender, race and socioeconomic status to obesity and obesity
      comorbidities in a sample of US adults.
AB  - OBJECTIVE: To examine the obesity-related chronic diseases in the US adult
      population according to gender, race and socioeconomic status. METHODS: Data from
      the 1994-1996 Continuing Survey of Food Intakes by Individuals (1994-1996 CSFII)
      conducted by the US Department of Agriculture/Agricultural Research Service
      (USDA/ARS) were used in the analysis. Relevant data included self-reported weight
      and height, self-reported physician-diagnosed diabetes mellitus, hypertension,
      heart disease and high serum cholesterol. Analysis was conducted according to
      gender, race, income level and education level. RESULTS: There was a graded
      increase in diabetes, hypertension and high serum cholesterol with increasing
      body weight in nearly all gender, racial and socioeconomic groups. Among the
      obese individuals, the prevalence of hypertension was higher in black subjects
      and the prevalence of diabetes, hypertension and heart disease was higher in
      individuals with lower education compared to their counterparts. The odds of
      having diabetes, hypertension, heart disease and high serum cholesterol increased
      with increasing body weight after adjusting for age, gender, race, income,
      education and smoking. CONCLUSION: Although cross-sectional in nature, our
      results suggest that the disease burden associated with obesity in the population
      may be substantial. This burden increases with increasing severity of obesity.
      Our findings support the current opinion that, although the nature of obesity
      related health risks is similar in all populations, the specific level of risk
      associated with a given level of obesity may be different depending on gender,
      race and socioeconomic condition.

PMID- 12187398
TI  - Prevalence of overweight and obesity and trends in body mass index in German pre
      school children, 1982-1997.
AB  - OBJECTIVE: To examine the prevalence of overweight and obesity in the entire
      population of 5- and 6-y-old children entering school in Germany, Bavaria, and to
      assess time trends over the last 15 y and the impact of ethnicity. DESIGN: Cross
      sectional studies were based on the obligatory school entry health examinations:
      all health districts of Bavaria in 1997 (n=127 735); three health districts every
      5 y from 1982 to 1997 (n=16 281). MEASUREMENTS: Body mass index (BMI; kg/m(2))
      was calculated and the prevalence of overweight and obesity was defined based on
      national and international agreed cut-off points. Ethnicity was measured as
      German and non-German nationality. RESULTS: The prevalence of overweight and
      obese children as defined by international reference values was 9.4 and 3.1% for
      5-y-old boys, 10.0 and 2.9% for 6-y-old boys, 12.2 and 3.3% for 5-y-old girls and
      12.4 and 3.3% for 6-y-old girls. The whole BMI distribution in non-German
      children compared to German children was shifted to the right with median values
      in non-German children 0.3-0.5 kg/m(2) higher. In these the prevalence of
      overweight/obesity was 1.9/2.4 times higher for boys and 1.5/1.9 times higher for
      girls. The time trend between 1982 and 1997 shows an increase of the BMI
      distribution in the upper percentiles, whereas the lower percentiles did not
      change substantially. The increased prevalences of overweight/obesity for both
      sexes as defined by international references increased from 8.5/1.8% in 1982 to
      12.3/2.8% in 1997. CONCLUSION: This large study on all children entering school
      in Bavaria in 1997 shows patterns of overweight and obesity which are comparable
      with other European data but are lower than US and Australian data. Increasing
      prevalences since 1982 indicate that overweight and obesity in children are of
      increasing public health importance in Bavaria. The upwards shift of the BMI
      distribution in non-German children needs further investigation.

PMID- 12187399
TI  - Long-term and recent time trends in the prevalence of obesity among Dutch men and
      women.
AB  - OBJECTIVE: To describe long-term and recent time trends in the prevalence of
      obesity by age and educational level. DESIGN: :Repeated cross-sectional
      population based monitoring studies. SETTING: Consultation Bureau Heart Project
      1976-1980, Monitoring Project on Cardiovascular Diseases 1987-1991 and Monitoring
      project on risk factors for chronic diseases (MORGEN-) project 1993-1997.
      SUBJECTS: A total of 29 141 men and women aged 37-43 y (1976-1997); and 21 926
      men and women aged 20-59 y (1993-1997). MEASUREMENTS: Body mass index, ie weight
      divided by height squared. RESULTS: Between 1976 and 1997 the prevalence of
      obesity increased from 4.9 to 8.5% among men and from 6.2 to 9.3% among women
      aged 37-43 y. Between 1993 and 1997, the prevalence of obesity among men aged 20
      59 y was 8.5% and increased by 0.54 percentage points per year (P<0.01). The
      prevalence of obesity among women was 9.6% and increased by 0.35 percentage
      points per year (P=0.07). The increase in the prevalence of obesity in the period
      1993-1997 was strongest in men with a relatively low educational level and in
      women with a high educational level. CONCLUSIONS: There has been a steady
      increase in the prevalence of obesity in the last quarter of the 20th century.
      Also, a recent increase in the prevalence of obesity has been seen. To stop the
      increase in the prevalence of obesity, effective strategies for the management
      and prevention of obesity need to be developed.

PMID- 12187400
TI  - Familial resemblance of body mass index and familial risk of high and low body
      mass index. A study of young men in Sweden.
AB  - OBJECTIVE: Male familial correlations in body mass index (BMI) were studied using
      a large nationwide dataset of Swedish military conscripts examined at age 18-19
      y. DESIGN: Record linkage was performed between Sweden's Military Service
      Conscription Register and the Multiple-Generation Register, enabling the
      identification of 92 869 families containing at least two brothers. Data on BMI
      at conscription was available for 196 743 sons and for 19 972 fathers. Pairs of
      relatives were used to estimate Pearson correlation coefficients for BMI, and to
      examine whether there are BMI intervals that show particularly strong familial
      resemblance. RESULTS: All biological family relations showed highly significant
      correlations for BMI: 0.28 (95% CI 0.27-0.29) for father-son pairs; 0.36 (0.35
      0.37) for full-brothers, 0.21 (0.18-0.24) for maternal half-brothers, and 0.11
      (0.08-0.14) for paternal half-brothers. Also, a significant correlation, of 0.06
      (0.01-0.11), was found for non-biological quasi father-son relations. Full
      brothers were more similar with respect to BMI at age 18 than father-son pairs,
      and maternal half-brothers were more similar than paternal half-brothers. The
      familial risk of having BMI values above or below various cut-offs was found to
      be equally strong for low BMI as for high BMI values. CONCLUSION: The almost
      twice as strong BMI correlation between maternal half-brothers as between
      paternal half-brothers illustrates the importance of factors of non-additive
      genetic origin, to the familial aggregation of BMI. The significant BMI
      association found between biologically unrelated individuals from the same family
      emphasizes that assortative mating (and regional clustering) should be taken into
      account when the heritability of BMI is estimated.

PMID- 12187401
TI  - Optimal cut-off values for obesity: using simple anthropometric indices to
      predict cardiovascular risk factors in Taiwan.
AB  - BACKGROUND: The increased health risks associated with obesity have been found to
      occur in Asians at lower body mass indices (BMIs). To determine the optimal cut
      off values for overweight or obesity in Taiwan, we examined the relationships
      between four anthropometric indices and cardiovascular risk factors. METHODS: The
      data were collected from four health-screening centers from 1998 to 2000 in
      Taiwan. Included were 55 563 subjects (26 359 men and 29 204 women, mean
      age=37.3+/-10.9 and 37.0+/-11.1 y, respectively). None had known major systemic
      diseases or were taking medication. Individual body weight, height, waist
      circumference (WC), and a series of tests related to cardiovascular risk (blood
      pressure, fasting plasma glucose, triglycerides, total cholesterol, low- and high
      density lipoprotein cholesterol) were assessed and their relationships were
      examined. Receiver operating characteristic (ROC) analysis was used to find out
      the optimal cut-off values of various anthropometric indices to predict
      hypertension, diabetes mellitus and dyslipidemia. RESULTS: Of the four
      anthropometric indices we studied, waist-to-height ratio (WHtR) in women was
      found to have the largest areas under the ROC curve (women=0.755, 95% CI 0.748
      0.763) relative to at least one risk factor (ie hypertension or diabetes or
      dyslipidemia). The optimal cut-off values for overweight or obesity from our
      study in men and women showed that BMIs of 23.6 and 22.1 kg/m(2), WCs of 80.5 and
      71.5 cm, waist-to-hip ratios (WHpR) of 0.85 and 0.76, and WHtR of 0.48 and 0.45,
      respectively, may be more appropriate in Taiwan. CONCLUSIONS: WHtR may be a
      better indicator for screening overweight- or obesity-related CVD risk factors
      than the other three indexes (BMI, WC and WHpR) in Taiwan. Our study also
      supported the hypothesis that the cut-off values using BMI and WC to define
      obesity should be much lower in Taiwan than in Western countries.

PMID- 12187402
TI  - Intake of sweet foods and counts of cariogenic microorganisms in relation to body
      mass index and psychometric variables in women.
AB  - OBJECTIVE: As a part of the SPAWN (Stockholm Pregnancy and Women's Nutrition)
      study, the intake of sweet foods (habitual and pre-menstrual intakes) and the
      number of cariogenic microorganisms in saliva was analysed in relation to body
      mass index (BMI) and psychometric variables. DESIGN: A cross-sectional study.
      SUBJECTS: Three hundred and sixty-two women with a median BMI of 24.2 kg/m(2)
      (range 17.5-47.8) and 45 y of age (range 34-64). METHODS: A questionnaire of
      sweet food intake, salivary counts of mutans streptococci and lactobacilli and a
      self-rating scale on psychometric variables (CPRS-S-A). RESULTS: The number of
      mutans streptococci correlated with BMI (P<0.05), indirectly indicating a higher
      intake of sweet foods in obese women. The reported energy intake of sweet foods
      (more specifically the intake of chocolate), correlated with CPRS scores
      (P<0.01), indicating that women with more severe psychiatric symptomatology have
      higher intakes of sweet foods. CONCLUSIONS: This study suggests that women with
      higher CPRS score have higher energy intakes of sweet foods, indicating a
      possible link between mood regulation and the intake of sweet food. SPONSORSHIP:
      Karolinska Institute Research Funds.

PMID- 12187403
TI  - Mechanism of the thermogenic effect of Metabolite 2 (BTS 54 505), a major
      pharmacologically active metabolite of the novel anti-obesity drug, sibutramine.
AB  - OBJECTIVE: To investigate the pharmacological mechanisms underlying the induction
      of thermogenesis by Metabolite 2 (M2; BTS 54 505), a major pharmacologically
      active metabolite of the anti-obesity drug, sibutramine. DESIGN: Adult female
      Wistar rats were treated with M2 or vehicle, with or without various monoamine
      receptor antagonists, prazosin, RS79948, metergoline, propranolol and
      (+)butaclamol. MEASUREMENTS: Colonic temperature and food intake at room
      temperature (21+/-1 degrees C), thermoregulatory behavioural response, operant
      responding for exogenous heat at -8 degrees C and oxygen consumption at
      thermoneutrality (29 degrees C). RESULTS: M2 (10 mg/kg, p.o.) significantly
      increased colonic temperature during the 4.5 h period following drug
      administration. This effect was abolished by the non-selective 5-HT receptor
      antagonist, metergoline (1 mg/kg, p.o.), and alpha(1)-adrenoceptor antagonist,
      prazosin (1 mg/kg, p.o.), measured at 1.5-2.5 h post-M2 administration, and was
      partially antagonized by each antagonist at 3.5-4.5 h. The non-selective beta
      adrenoceptor antagonist, propranolol (1 mg/kg, p.o.), had no effect on the M2
      induced increase in colonic temperature, whereas at 20 mg/kg (p.o.), propranolol
      partially inhibited the effect of M2 on colonic temperature. By contrast, the
      selective alpha(2)-adrenoceptor antagonist, RS79948 (1 mg/kg, p.o.), and the
      D2/D1 receptor antagonist, (+)butaclamol (200 micro g/kg, p.o.), did not alter
      the effect of M2 on colonic temperature. In the thermoregulatory study, M2 (10
      mg/kg, i.p.)-treated rats required significantly less radiant heat at -8 degrees
      C to maintain body temperature, and this effect was not affected by the D2/D1
      receptor antagonist (+)butaclamol (100 micro g/kg(-1), i.p.). The hypophagia
      induced by M2 (10 mg/kg) measured up to 24 h was partially antagonized by the
      alpha(1)-adrenoceptor antagonist, prazosin, whereas metergoline, RS79948,
      propranolol and (+)butaclamol had no effect on M2-induced hypophagia. CONCLUSION:
      It is concluded that 5-HT, alpha(1)- and beta(3)-adrenoceptors are involved in
      the induction of thermogenesis by M2, whereas the hypophagic effect is mainly
      mediated via alpha(1)-adrenoceptors. These findings are consistent with M2
      increasing 5-HT and noradrenaline tone via potent reuptake inhibition which
      subsequently results in increased efferent sympathetic activity to brown adipose
      tissue (BAT).

PMID- 12187404
TI  - Does using the Internet facilitate the maintenance of weight loss?
AB  - OBJECTIVE: The purpose of this study was to investigate the effectiveness of a
      weight maintenance program conducted over the Internet. DESIGN: Longitudinal,
      clinical behavioral weight loss trial with 6-month in-person behavioral obesity
      treatment followed by a 12-month maintenance program conducted both in-person
      (frequent in-person support; F-IPS, minimal in-person support; M-IPS) and over
      the Internet (Internet support; IS). SUBJECTS: A total of 122 healthy, overweight
      adults (age=48.4+/-9.6, BMI=32.2+/-4.5 kg/m(2), 18 male) MEASUREMENTS: Body
      weight, dietary intake, energy expended in physical activity, attendance, self
      monitoring, comfort with technology. RESULTS: Results (n=101) showed that weight
      loss did not differ by condition during treatment (8.0+/-5 vs 11+/-6.5 vs 9.8+/
      5.9 kg, P=0.27 for IS, M-IPS and F-IPS, respectively). The IS condition gained
      significantly more weight than the F-IPS group during the first 6 months of
      weight maintenance (+2.2+/-3.8 vs 0+/-4 kg, P<0.05) and sustained a significantly
      smaller weight loss than both in-person support groups at the 1 y follow-up (
      5.7+/-5.9 vs -10.4+/-9.3 vs -10.4+/-6.3 kg, P<0.05 for IS, M-IPS and F-IPS,
      respectively). Attendance at maintenance meetings was greater for the F-IPS than
      the IS condition over the 1 y maintenance program (54 vs 39%, P=0.04).
      Acceptability of assigned condition was higher for subjects in the F-IPS than IS
      condition. CONCLUSION: The results of this study suggest that Internet support
      does not appear to be as effective as minimal or frequent intensive in-person
      therapist support for facilitating the long-term maintenance of weight loss.

PMID- 12187405
TI  - Effects of cognitive-behavioural therapy on health-related quality of life in
      obese subjects with and without binge eating disorder.
AB  - OBJECTIVE: To measure the effects of cognitive-behavioural therapy on health
      related quality of life (HRQL) in obese patients, in relation to binge eating
      disorder. DESIGN: Longitudinal, clinical intervention study consisting of
      structured sessions of cognitive-behavioural therapy, preceded by sessions
      chaired by a psychologist in subjects with binge eating. SUBJECTS: Two groups of
      obese patients (92 treated by cognitive-behavioural therapy (77 females); 76
      untreated controls (67 female), selected from the waiting list (control group)).
      Of 92 treated patients, 46 had a binge eating disorder at psychometric testing
      and structured clinical interview. MEASUREMENTS: Health-related quality of life
      by means of Short-Form 36 questionnaire at baseline and after 3-5 months.
      RESULTS: Cognitive-behavioural treatment produced an average weight loss of 9.4+/
      7.5 kg, corresponding to a BMI reduction of 3.48+/-2.70 kg/m(2). No changes were
      observed in the control group. All scales of HRQL improved in treated subjects
      (by 5-19%). In obese subjects with binge eating weight loss was lower in
      comparison to non-bingers (7.7+/-8.1 vs 11.1+/-6.6; P=0.034). However, the
      improvement in HRQL was on average larger, and significantly so for Role
      Limitation-Physical (P=0.006), Role Limitation-Emotional (P=0.002), Vitality
      (P=0.003), Mental Health (P=0.032) and Social Functioning (P=0.034). Bodily Pain
      was the sole scale whose changes paralleled changes in body weight. CONCLUSIONS:
      The positive effects of cognitive-behavioural therapy, mainly in subjects with
      binge eating, largely outweigh the effects on body weight, resulting in a
      significant change in self-perceived health status.

PMID- 12187406
TI  - Possible risk factors in the development of eating disorders in overweight pre
      adolescent girls.
AB  - OBJECTIVES: To investigate concerns about weight, shape and eating, dietary
      restraint, self-esteem and symptoms of depression in overweight girls. To
      investigate the relationship between concerns and self-esteem and depressive
      symptoms in this group. METHOD: Eighteen overweight girls and 18 average-weight
      girls completed the child version of the Eating Disorders Examination, the Harter
      Self-Perception Profile and the Short Moods and Feelings Questionnaire. RESULTS:
      Overweight girls had more concerns about weight, shape and eating and attempted
      dietary restraint more often. They had more negative self-esteem related to their
      athletic competence, physical appearance and global self-worth and more symptoms
      of depression. There was an association between concerns and self-esteem based on
      physical appearance in the overweight group. CONCLUSION: Overweight girls show
      some of the psychological features associated with the development of eating
      disorders, including a link between concerns and self-esteem based on physical
      appearance. This may help to explain why childhood obesity increases the risk of
      a later eating disorder.

PMID- 12187407
TI  - Does the first pregnancy precipitate age-related fat deposition?
AB  - Excessive accumulation of fat in women of childbearing age is a concern, since
      obesity is an important cause of morbidity and mortality. Deposition of fat
      during pregnancy, which is not metabolized during lactation, may contribute.
      However, the individual effects of age and gravidity on fat accumulation have not
      been disentangled. Based on multiple linear regression analysis of anthropometric
      data from 1113 pregnant women from Zimbabwe, we found evidence to suggest that
      fat deposition is an effect of age rather than gravidity that is precipitated by
      the first pregnancy.

PMID- 12187408
TI  - The chlorophyll-derived metabolite phytanic acid induces white adipocyte
      differentiation.
AB  - Phytanic acid is a derivative of the phytol side-chain of chlorophyll. It appears
      in humans following the ingestion of fat-containing foods and is present in human
      blood at a low micromolar concentration. It may activate retinoid X receptors
      (RXR) or peroxisome proliferator-activated receptor (PPAR) alpha in vitro.
      Phytanic acid induced the adipocyte differentiation of 3T3-L1 cells in culture as
      assessed by accumulation of lipid droplets and induction of the aP2 mRNA marker.
      This effect was mimicked by a synthetic activator of RXR but not by a PPARalpha
      agonist or by palmitic acid. In human pre-adipocytes in primary culture, phytanic
      acid also induced adipocyte differentiation. These findings indicate that
      phytanic acid may act as a natural rexinoid in adipose cells and suggest a
      potential use in the treatment of human type 2 diabetes and obesity.

PMID- 12187410
TI  - The use of autologous autoclaved bone in orbital reconstruction after
      exenteration for invasive cutaneous carcinoma.
AB  - PURPOSE: To describe a technique for reconstructing the orbital bony architecture
      after invasion by tumour. METHODS: Orbital bone invaded by tumour was
      osteotomized (post-exenteration), autoclaved to remove tumour cells, and then
      refixated in order to re-establish the normal orbital anatomy. RESULTS: Despite
      some shrinkage of the bone fragment in the autoclaving process, after refixation
      the contour and topography of the bony orbit was essentially normal. CONCLUSION:
      Autoclaved bone can be used to reconstruct the exenterated orbit; it is a fast
      and technically simple strategy for maintaining orbital anatomy when faced with
      bony invasion by tumour.

PMID- 12187411
TI  - Gelatinous polyethylene in the treatment of the anophthalmic cavity.
AB  - PURPOSE: Gelatinous polyethylene (GP) has been used as an orbital implant to
      evaluate volume maintenance and tissue reaction in the anophthalmic socket in a
      rabbit model. METHODS: Twenty-eight Norfolk white rabbits underwent unilateral
      evisceration with placement of 2 ml GP (GP group - 16 animals) or 2 ml 0.9%
      sodium chloride solution (Control group - 12 animals). Animal behavior,
      postoperative tissue response and socket conditions were evaluated. The animals
      were sacrificed at 7, 15, 30 and 60 days after the surgery and the bulbs were
      enucleated; volume maintenance and histopathological evaluation were done in the
      enucleated bulbs. The results were submitted to statistical analysis. RESULTS:
      All animals showed normal behavior. The orbital volume maintenance was better in
      the GP group. Histopathology in the GP animals showed mild tissue inflammation
      throughout the evaluation period and a thin pseudocapsule formation surrounding
      the orbital implant material. CONCLUSION: The clinical findings, good orbital
      volume maintenance and mild inflammatory tissue response make GP a good choice to
      replace the lack of volume in anophthalmic socket reconstruction.

PMID- 12187412
TI  - Frontalis suspension sling using a silicone rod in patients affected by myogenic
      blepharoptosis.
AB  - The charts of 10 patients affected by myogenic ptosis who underwent surgical
      correction by means of a frontalis suspension sling using a silicone rod were
      reviewed. The patients included in the study were affected by ptosis secondary to
      myasthenia gravis (MG), chronic progressive external ophthalmoplegia (CPEO) or
      mitochondrial myopathy (MM). In every patient the ptosis was severe (MRD( 1) < 2
      mm), with the eyelid partially or totally occluding the visual axis; levator
      function was poor (<5 mm), Bell's phenomenon was poor or absent and the
      orbicularis function was reduced. Final eyelid height, patient satisfaction and
      the presence of complications were our main outcome measures. Analysis of the
      results showed that the ptosis was corrected in every patient with a clear visual
      axis. One patient with absent Bell's and poor levator function had exposure
      keratopathy resistant to medical treatment and required surgical revision. We
      believe that the frontalis suspension sling is safe, effective and is the
      procedure of choice for patients affected by poor-function acquired ptosis. A
      silicone rod, because of its elasticity, is the material of choice in this
      selected category of patients.

PMID- 12187413
TI  - Interactive image guidance for surgical localization of orbital apical tumors.
AB  - The surgical management of orbital apex tumors is difficult. Intervention in this
      small posterior space is fraught with complications. We have used an interactive
      image guidance system to successfully biopsy and resect three tumors at the
      orbital apex without significant surgical morbidity. These three cases are
      presented. These interactive image guidance systems have revolutionized skull
      base surgery and have a role in the surgical management of orbital apex tumors.

PMID- 12187414
TI  - Neurofibroma of the lacrimal sac.
AB  - Neurofibroma is an extremely rare neural tumor of the lacrimal sac. We present a
      case of neurofibroma of the lacrimal sac in a 45-year-old lady. Based on the
      history of intermittent epiphora, presence of a mass in the lacrimal sac region,
      dacryocystogram suggestive of space occupying lesion within the lacrimal sac and
      computed tomographic image of a tumor lying in the lacrimal fossa region, a
      tentative diagnosis of lacrimal sac neoplasm was made. Excision of the tumor with
      repair of the lacrimal sac was performed. Histopathology proved it to be
      neurofibroma of the lacrimal sac. Until now, only four cases have been reported
      worldwide. The paucity of reported cases limits our knowledge regarding the
      natural course, treatment, results and prognosis of this tumor.

PMID- 12187416
TI  - Fibrous histiocytoma in primary pterygium.
AB  - Fibrous histiocytoma, a mesenchymal tumor, although reported to develop in
      various ocular structures with a variable frequency, has never been found within
      a pterygium. We report the case of a 50-year-old female who had had a pterygium
      for the last six years and had developed a tumor within it one and a half years
      ago. The tumor was excised along with the pterygium. On histopathological
      examination the tumor was found to be a benign fibrous histiocytoma arising from
      within the pterygium.

PMID- 12187417
TI  - Intra-tarsal cysticercosis of the lower lid.

PMID- 12187415
TI  - Ocular surface squamous neoplasia: report of an unusual case and review of the
      literature.
AB  - OBJECTIVE: To describe a case of leukoplakia and underlying intraepithelial
      squamous cell neoplasia of the palpebral conjunctiva presenting in a patient
      wearing an ocular prosthesis. METHODS: The clinical presentation,
      histopathological findings and surgical outcome are described in a 62-year-old
      man in whom leukoplakic lesions of the palpebral conjunctiva in a socket fitted
      with an ocular prosthesis were noted in addition to squamous cell carcinoma of
      the lower lid skin. RESULTS: Histopathological examination revealed islands of
      squamous cell carcinoma in the skin lesion and squamous cell carcinoma-in-situ in
      the leukoplakic conjunctival specimen. Successful tumour excision and lid
      reconstruction were performed. CONCLUSION: This report highlights the successful
      treatment of long-standing conjunctival squamous cell carcinoma-in-situ
      associated with an ocular prosthesis and a general tendency to pre-neoplastic
      lesions of the skin. Regular examination of the sockets of patients wearing long
      standing ocular prostheses is recommended.

PMID- 12187418
TI  - Primary mucinous meningioma of bone.

PMID- 12187419
TI  - Pigmented conjunctival neoplasms.
AB  - Pigmented lesions of the conjunctiva are not rare. They may be acquired,
      congenital, benign or malignant. In the present paper, the author provides a
      brief review, in a non-exhaustive manner, of the common melanocytic
      pigmentations, with more emphasis on the malignant and pre-malignant variants.

PMID- 12187421
TI  - Differences between screening sites in a glaucoma screening program.
AB  - OBJECTIVE: To determine the differences in demographic variables, glaucoma risk
      factors, and visual acuity by type of screening site. METHODS: We conducted
      glaucoma screenings throughout the city of Baltimore. A questionnaire collected
      information about age, race, and risk factors: having a relative with glaucoma,
      having diabetes, having a past eye injury or surgery, and not having an eye
      examination within two years. We also tested visual acuity and visual fields. We
      categorized screening sites into work places, senior centers, health fairs, and
      church groups, and created age-race groups by combining age and race categories.
      RESULTS: This study is based on 1,366 people screened at 42 different sites. The
      majority of people screened were African-American (65%) and female (58%), with a
      mean age of 48 years. We found significant age and race differences between the
      screening sites. After stratifying by age-race groups, we found statistically
      significant associations between screening sites and not having a recent eye
      examination (P =.009) and visual acuity (P =.001). Health fairs had the largest
      percentage of people not having a recent eye examination, and senior centers had
      the largest percentage of people with poor visual acuity. CONCLUSIONS: Our data
      showed differences in age and race between screening sites. After conducting
      stratified analysis, differences between screening sites and recent eye
      examinations and visual acuity persisted. These differences in screening sites,
      as well as objectives of the vision screening, should be considered when planning
      a screening program to help focus the program on appropriate high-risk subgroups
      of the population.

PMID- 12187422
TI  - Causes of uveitis at The Eye Center in Saudi Arabia: a retrospective review.
AB  - AIMS AND BACKGROUND: The main objective of this study was to determine the causes
      of uveitis at a referral center in Riyadh, Saudi Arabia. METHODS: We carried out
      a retrospective review of clinical records of 200 uveitis cases referred to The
      Eye Center, a referral center in Riyadh, Saudi Arabia. There were 120 (60%) males
      and 80 (40%) females with an age range of 7 to 91 years and a mean age of 35 (SD
      +/- 17). Patients had complete ophthalmic and medical examinations. Laboratory
      studies were requested whenever indicated. Patients were followed up for a
      minimum of 12 months. RESULTS: In the period 1995-2000, we encountered 200 cases
      of uveitis among a total of 20,191 consecutive new cases, yielding a prevalence
      of 1%. Acute anterior uveitis of undetermined origin was found in 58 (29%) of 200
      patients. There were 13 (6.5%) cases of Behcet's disease, 7 (3.5%) of Fuchs'
      heterochromic iridocyclitis, 6 (3%) of sarcoidosis, and 5 (2.5%) patients had
      Vogt-Koyanagi-Harada syndrome (VKH). Among the infectious causes, herpetic
      uveitis was found in 32 (16%) patients, tuberculosis in 21 (10.5%), and
      toxoplasmosis in 13 (6.5%) cases. Seventeen (8.5%) cases were of miscellaneous
      origin and in 28 (14%) cases the etiologic diagnosis was undetermined.
      CONCLUSION: Acute anterior uveitis of undetermined origin was the most common
      cause of uveitis, followed by Behcet's disease. Herpetic uveitis was the most
      common infectious cause of uveitis. Ocular tuberculosis and toxoplasmosis were
      found to be common causes of infectious uveitis at this referral center in Saudi
      Arabia.

PMID- 12187423
TI  - Evaluation of E-optotypes as a screening test and the prevalence and causes of
      visual loss in a rural population in SW Uganda.
AB  - BACKGROUND: Few population-based eye surveys have been conducted in sub-Saharan
      Africa, limiting the quality of epidemiological information on visual loss from
      Africa. In the present paper, we describe the prevalence of visual loss in rural
      Uganda and the screening accuracy of E-optotypes when used by non-medical staff.
      METHODS: Residents of 15 neighbouring villages were screened for visual loss
      (<6/18 in either eye) using Snellen's E-optotypes. Individuals who failed were
      initially referred to an ophthalmic clinical officer (OCO), who retested visual
      acuity and subsequently referred to an ophthalmologist to determine the cause of
      visual loss. Subjects from two villages (248 individuals) who passed visual
      acuity screening were re-examined by the OCO to estimate the accuracy of the
      screening procedure. RESULTS: Of the 4076 adults (aged 13 years and over, 69.3%
      of the censused population) who participated, 191 (4.7%) failed the vision
      screening criteria and 648 (15.9%) had non-vision impairing conditions. The
      prevalence of visual loss was at least 3.9%: 0.4% had bilateral blindness, 1.6%
      had bilateral visual impairment, 0.7% had unilateral blindness and 1.2%
      unilateral visual impairment. Cataract was the leading cause for all categories
      of visual loss except bilateral blindness, for which suspected glaucoma was most
      frequent. Refractive errors were the second leading cause of bilateral and
      unilateral visual impairment. Based on one subject (0.4%) in the validation
      sample who was found to have low vision, we estimated the sensitivity and
      specificity of E-optotypes for detecting visual loss to be 93% and 99%,
      respectively. CONCLUSIONS: Cataract and refractive errors were responsible for
      most of the visual loss in rural Uganda. Snellen's E-optotypes provide a suitable
      cost-saving tool for conducting population-based eye surveys in sub-Saharan
      Africa.

PMID- 12187424
TI  - Does clinical diagnosis indicate ocular chlamydial infection in areas with a low
      prevalence of trachoma?
AB  - The WHO has initiated a global program to eliminate trachoma. This program
      includes mass antibiotic administrations to reduce the prevalence of Chlamydia
      trachomatis, the causative agent in trachoma. DNA amplification tests are the
      most sensitive methods to diagnose C. trachomatis infection, but are expensive
      and not typically performed in trachoma-endemic areas. Trachoma programs use
      clinical examination to determine which communities and which individuals within
      communities would benefit from antibiotic treatment, so understanding the
      relationship between clinical activity and chlamydial infection is important. In
      this study, we determine what percent of individuals with clinically active
      trachoma are infected with chlamydia in low prevalence communities of China and
      Nepal (with <10% clinical activity in children), and compare this against a high
      prevalence community of Nepal (with >30% clinical activity in children). In the
      low prevalence areas, only 8% clinically active cases had evidence of chlamydia.
      In the high prevalence community, 70% of clinically active cases harbored
      chlamydia. These results imply that clinical activity is less indicative of
      infection at a lower prevalence. In the context of a trachoma program, both
      clinically active cases and the community as a whole may stand to benefit less
      from antibiotic treatment in lower prevalence areas.

PMID- 12187425
TI  - Prevalence and causes of severe visual impairment and blindness in children in
      Mongolia.
AB  - BACKGROUND: Reliable epidemiological data on the prevalence and causes of visual
      loss in children are difficult to obtain, but are essential for planning. No such
      data are available from Mongolia. AIM: To determine the prevalence and causes of
      severe visual impairment and blindness (SVI/BL) in children from a defined area
      of Mongolia, using several methods of identification. METHODS: Children with
      presenting visual acuities of <6/60 in the better eye who lived in 10 of the 18
      provinces (Aimaks) were identified 1) by family doctors 2) in the school for the
      blind 3) by visiting eye departments in the capital. All eligible children were
      examined (or data extracted from hospital records) and the cause of visual loss
      determined using the WHO classification system. RESULTS: Sixty-four children with
      SVI/BL before refraction were identified who lived in the 10 study Aimaks. They
      were recruited by family doctors (52); by home visits (3); from hospital records
      (4); or from the school for the blind (5). The prevalence of SVI/BL before
      refraction was 0.19/1,000 children (95% CI 0.16-0.22), decreasing to 0.16/1,000
      after refraction (95% CI 0.13-0.19) but there was considerable variation from
      Aimak to Aimak. The major causes of SVI/BL were lesions of the lens (34%),
      central nervous system disorders (19%), lesions of the whole globe (e.g.
      microphthalmos) (14%), and retinal conditions (12.5%). Hereditary factors were
      responsible for 27% of causes, and 17% of children were blind following acquired
      conditions of childhood. The underlying cause could not be determined in 48%. The
      causes of SVI/BL was analysed in a further 16 children who lived outside the
      study Aimaks to compare the causes in children in special education with those
      not in schooling, and by age. CONCLUSION: The prevalence estimate obtained was
      lower than anticipated, and possible reasons are discussed. The pattern of causes
      of SVI/BL is similar to that in children in schools for the blind in China, but
      is very different from other Asian countries. Meningococcal meningitis was the
      most common preventable cause of SVI/BL, and immunisation is being considered.
      Other preventable causes were rare, and the majority of children needing surgical
      intervention had already been identified and referred for treatment. The control
      of blindness in children could possibly be improved by better management of
      conditions requiring surgery, and by the provision of low vision devices.

PMID- 12187427
TI  - Infantile and childhood retinal blindness: a molecular perspective (The
      Franceschetti Lecture).
AB  - Much progress has been made in the past five years in the understanding of Leber
      congenital amaurosis (LCA) and allied early-onset retinal dystrophies, various
      forms of stationary sensory retinal blindness, and genes that are involved in the
      development of the retina. Uncomplicated Leber congenital amaurosis has been
      associated with mutations of six genes: GUCY2D (encoding RetGC-1) at 17p13.1,
      RPE65 at 1q31, CRX at 19q13.3, AIPLI at 17p13.1, CRB1 at 1q31-3, and RPGRIP at
      14q11. A similar early-onset severe retinal degeneration phenotype has been
      associated with mutation of TULP1 at 6p21.3. Leber appreciated that the condition
      he described merged with the phenotypes of early childhood-onset severe retinal
      degenerations. This insight has been confirmed at the molecular level for
      mutations of GUCY2D, RPE65, CRX, AIPL1, and CRB1, which cause not only LCA, but
      also early-childhood and even adult-onset retinal degenerations. This paper
      reviews the new finding of LCA from mutations of CRB1 and discusses the molecular
      basis of X-linked blue monochromacy, autosomal recessive congenital achromatopsia
      from mutations of the genes for ACHM2 (CNGA3) and ACHM3 (CNGB3), X-linked
      congenital stationary night blindness (CSNB) from mutations of CACNA1F
      (incomplete CSNB) and NYX (complete CSNB), and the enhanced S-cone syndrome from
      mutation of the developmental gene, NR2E3 at 15q23, which appears to regulate the
      development of M- and L-cones from S-cones. These discoveries have opened new
      areas of cellular and developmental biology for future research into the causes
      of retinal blindness.

PMID- 12187426
TI  - Use of vitamin and zinc supplements and age-related maculopathy: the Blue
      Mountains Eye Study.
AB  - PURPOSE: To investigate relationships between vitamin and zinc supplement use and
      age-related maculopathy in a population-based sample. METHODS: We studied 2873
      (79%) of the 3654 participants aged 49- 97 years who attended the cross-sectional
      Blue Mountains Eye Study and completed a detailed food frequency questionnaire,
      including type, dose and duration of supplement use. ARM was assessed during a
      masked grading of macular photographs. Odds ratios (OR) and 95% confidence
      intervals (CI) were calculated using logistic regression. RESULTS: After
      adjusting for multiple confounders, we found that no vitamin or zinc supplements
      were significantly associated with reduced prevalence of any ARM lesions in
      either eye. The OR for use of any vitamin supplement was 1.3 (CI 0.9-1.7, p =
      0.11) for individuals with any retinal pigment changes. It was 1.1 (CI 0.8-1.5, p
      = 0.59) for those with any soft (large) drusen and 1.5 (CI 0.7-3.0, p = 0.31) for
      those with late ARM lesions. The lack of association between supplement intake
      and ARM persisted regardless of their duration of use, dose or the smoking status
      of participants. The Breslow-Day test for heterogeneity was 0.24 with an OR for
      early ARM lesions among smokers of 0.7 (CI 0.4-1.3, p = 0.27), and 1.2 (CI 0.9
      1.5, p = 0.24) among non-smokers. CONCLUSION: This cross-sectional population
      based study investigated associations between vitamin and zinc supplement use and
      the prevalence of ARM lesions. Our findings provide no support for a protective
      association between vitamin and zinc supplement use and lesions indicating early
      ARM. The small numbers of subjects with late ARM lesions precluded any detailed
      investigation of benefits from supplement use on the prevalence of these lesions.

PMID- 12187428
TI  - Electroretinographic changes in the inner retinal layers of the retained eyes of
      patients with sporadic unilateral retinoblastoma.
AB  - PURPOSE: Examination of retinal function as measured by flash electroretinogram
      (ERG) including oscillatory potentials (OPs) and pattern electroretinogram (PERG)
      in a series of patients with unilateral sporadic retinoblastoma. PATIENTS:
      Studies were undertaken in the retained eye (without clinical evidence of
      retinoblastoma) of 13 patients with sporadic unilateral retinoblastoma and in 13
      healthy controls. METHODS: Standard flash ERG including scotopic OPs and PERG
      recordings were performed in accordance with the International Society for
      Clinical Electrophysiology of Vision (ISCEV) standards. RESULTS: Statistically
      significant differences between the studied and the control groups were observed
      with flash ERG (OP1 amplitude increase, p < 0.003; photopic flicker amplitude
      increase, p < 0.05) and PERG (P50 latency increase, p < 0.008). CONCLUSIONS:
      Inner retinal layer dysfunction may be a characteristic feature of individuals
      with unilateral sporadic retinoblastoma.

PMID- 12187429
TI  - Clinical features of achromatopsia in Swedish patients with defined genotypes.
AB  - PURPOSE: To describe the clinical phenotype, with emphasis on the
      electrophysiological findings, of patients with autosomal recessive rod
      monochromacy (RM) and defined mutations in the CNGA3/CNGB3 genes. METHODS: RM
      patients from eight different families were included in the study. Their
      genotypes were determined by DNA sequencing and/or RFLP analysis of PCR-amplified
      genomic segments of the CNGA3 and CNGB3 genes. For comparison, we investigated
      one patient with blue-cone monochromacy (BCM). The clinical examination included
      best-corrected visual acuity, fundus examination, and full-field ERG. In six
      patients, the examination was complemented by multifocal ERG (MERG). RESULTS:
      Three patients had three different CNG3A genotypes. Five patients were homozygous
      and one patient compound heterozygous for a 1-bp deletion (1148delC) in the CNGB3
      gene. All patients examined presented with a visual acuity of 0.1-0.15. Small
      residual cone responses were noted in four young RM patients. The oldest patient
      examined (age 47 years) presented with pigmentary changes in the mid-peripheral
      retina and concentric constrictions of the visual fields. CONCLUSIONS: Patients
      with RM and mutations in the CNGA3/CNGB3 genes presented a similar clinical
      phenotype, confirming the essential function of both the alpha- and beta-subunits
      of the cGMP-gated cation channel in cone photoreceptor function. Small remaining
      cone responses in a few of the younger patients and mid-peripheral pigmentary
      degenerations in the oldest patient examined indicate that there could be some
      degree of progression in retinal dysfunction in at least some patients with RM.

PMID- 12187430
TI  - Mutational analysis of the RB1 gene in Indian patients with retinoblastoma.
AB  - Twenty-one probands, twelve with bilateral and nine with unilateral
      retinoblastoma, were screened for mutations in the RB1 gene using genomic DNA
      from peripheral blood leukocytes as well as tumors. Amplification of individual
      exons and flanking regions of the RB1 gene were carried out, followed by direct
      sequencing of the amplified products. Sequences of affected individuals were
      compared with those of controls. Mutations were identified in seven patients,
      five with bilateral and two with unilateral retinoblastoma. Six out of seven
      mutations involved the formation of premature termination codons by means of
      single base substitutions (2), frameshifts due to splice-site mutations (2), or
      deletion and duplication (2). One missense mutation was identified. Of the
      remaining fourteen patients, seven with bilateral disease had no mutations in
      peripheral blood (7 cases) or tumors (3/7 cases). Analysis of the peripheral
      blood of seven patients with unilateral disease also showed no mutations.
      Mutations were detected in about one-third of the cases, suggesting that
      hemizygous deletions at the RB1 locus or mutations outside the coding regions of
      RB1 may be responsible for the disease in the remaining patients.

PMID- 12187431
TI  - Identification of a novel VMD2 mutation in Japanese patients with Best disease.
AB  - PURPOSE: To report a novel VMD2 gene mutation in a Japanese family with Best
      disease and the clinical phenotype of the patients. PATIENTS AND METHODS:
      Mutational analysis for VMD2 was performed by direct sequencing in two members of
      a Japanese family with Best disease. Clinical examination included visual acuity,
      electro-oculography (EOG), and fundus examination. RESULTS: A T990C mutation of
      the VMD2 gene was found in the 20-year-old boy and his 47-year-old mother. The
      boy had bilateral vitelliform cyst-like lesions in both eyes and showed a
      pathological Arden ratio of 1.0 on EOG. The mother had a normal fundus appearance
      with an Arden ratio of 1.0 on EOG. CONCLUSION: A novel disease-causing mutation
      in the VMD2 gene (T990C) was found in Japanese patients with Best disease.

PMID- 12187432
TI  - An infant with Down syndrome and retinoblastoma. A possible non-fortuitous
      association.

PMID- 12187433
TI  - Molecular genetics and the transformation of medicine.

PMID- 12187434
TI  - Historical development of the concept of the gene.
AB  - The classical view of the gene prevailing during the 1910s and 1930s comprehended
      the gene as the indivisible unit of genetic transmission, genetic recombination,
      gene mutation and gene function. The discovery of intragenic recombination in the
      early 1940s led to the neoclassical concept of the gene, which prevailed until
      the 1970s. In this view the gene or cistron, as it was now called, was divided
      into its constituent parts, the mutons and recons, materially identified as
      nucleotides. Each cistron was believed to be responsible for the synthesis of one
      single mRNA and concurrently for one single polypeptide. The discoveries of DNA
      technology, beginning in the early 1970s, have led to the second revolution in
      the concept of the gene in which none of the classical or neoclassical criteria
      for the definition of the gene hold strictly true. These are the discoveries
      concerning gene repetition and overlapping, movable genes, complex promoters,
      multiple polyadenylation sites, polyprotein genes, editing of the primary
      transcript, pseudogenes and gene nesting. Thus, despite the fact that our
      comprehension of the structure and organization of the genetic material has
      greatly increased, we are left with a rather abstract, open and general concept
      of the gene. This article discusses past and present contemplations of genes,
      genomes, genotypes and phenotypes as well as the most recent advances of the
      study of the organization of genomes.

PMID- 12187435
TI  - The molecular turn in psychiatry: a philosophical analysis.
AB  - Biological psychiatry has been dominated by a psychopharmacologically-driven
      neurotransmitter dysfunction paradigm. The objective of this paper is to explore
      a reductionist assumption underlying this paradigm, and to suggest an improvement
      on it. The methods used are conceptual analysis with a comparative approach,
      particularly using illustrations from the history of both biological psychiatry
      and molecular biology. The results are that complete reduction to physicochemical
      explanations is not fruitful, at least in the initial stages of research in the
      medical and life sciences, and that an appropriate (non-reducible) integrative
      principle--addressing a property of the whole system under study--is required for
      each domain of research. This is illustrated in Pauling's use of a topological
      integrative principle for the discovery of the functioning of proteins and in
      Watson and Crick's use of the notion of a genetic code as an integrative
      principle for the discovery of the structure of genes. The neurotransmitter
      dysfunction paradigm addresses single molecules and their neural pathways, yet
      their interactions within the CNS as a whole seem most pertinent to mental
      disorders such as schizophrenia. The lack within biological psychiatry of an
      integrative principle addressing a property of the CNS as a whole may be
      responsible for the empirical failure of orthomolecular psychiatry, as well as
      for the central role that serendipity has played in the study of mental
      disorders, which is dominated by the neurotransmitter paradigm. The conclusion is
      that research in biological psychiatry may benefit from using, at least
      initially, some integrative principle(s) addressing a property of the CNS as a
      whole, such as connectionism or a hierarchical notion.

PMID- 12187436
TI  - Therapeutic cloning: from consequences to contradiction.
AB  - The British Parliament legalized therapeutic cloning in December 2000 despite
      opposition from the European Union. The watershed event in Parliament's move was
      the active and unprecedented government support for the generation and
      destruction of human embryonic life merely as a means of medical advancement.
      This article contends that the utilitarian analysis of this procedure is
      necessary to identify the real world risks of therapeutic cloning but
      insufficient to identify the breach of defensible ethical limits that this
      procedure represents. A value-oriented approach to Kantian ethics demonstrates
      that the utilitarian endorsement of therapeutic cloning entails a contradiction
      of the necessity of human vulnerability and a faulty valuation of the human
      embryo. The concern is that a narrow utilitarian focus ultimately commodifies
      human embryonic life and preferences outcomes as the sole determinant of moral
      value.

PMID- 12187437
TI  - Human cloning: three mistakes and an alternative.
AB  - The current debate on the ethics of cloning humans is both uninspired and
      uninspiring. In large measure this is because of mistakes that permeate the
      discourse, including the mistake of thinking that cloning technology is strictly
      a reproductive technology when it is used to create whole beings. As a result,
      the challenge this technology represents regarding our understanding of ourselves
      and the species to which we belong typically is inappropriately downplayed or
      exaggerated. This has meant that important (albeit disquieting) societal issues
      and species-type concerns have not been fully explored. This paper, intended as a
      corrective, suggests that we take an alternate view of human cloning as both an
      enhancement and a reproductive technology. This proposed shift in the framework
      for analysis counters the current narrow framing of the issues and introduces new
      questions about the prospect of modifying the species.

PMID- 12187438
TI  - Extending the human life span.
AB  - Research into the mechanisms of aging has suggested the possibility of extending
      the human life span. But there may be evolutionary biological reasons for
      senescence and the limits of the cell cycle that explain the infirmities of aging
      and the eventual demise of all human organisms. Genetic manipulation of the
      mechanisms of aging could over many generations alter the course of natural
      selection and shift the majority of deleterious mutations in humans from later to
      earlier stages of life. This could harm people in the distant future by making
      them more susceptible to premature disease and mortality. Thus there are
      biological and moral reasons to carefully consider the implications of exploiting
      this technology on a broad scale to extend the lives of people in the present and
      near future.

PMID- 12187439
TI  - Extending human lifespan and the precautionary paradox.
AB  - This paper argues that a precautionary approach to scientific progress of the
      sort advocated by Walter Glannon with respect to life-extending therapies
      involves both incoherence and irresolvable paradox. This paper demonstrates the
      incoherence of the precautionary approach in many circumstances and argues that
      with respect to life-extending therapies we have at present no persuasive reasons
      for a moratorium on such research.

PMID- 12187440
TI  - Education in a genomic world.
AB  - If a transformation in medicine occurs in the wake of the Human Genome Project,
      its likely focus will be prevention, a logical extension of the lessons of
      variation and individuality inherent in molecular genetics. The transformation of
      medicine will require a transformation in genetics education as well, focusing on
      the development of genetic literacy that allows patient and provider to
      collaborate as partners in health promotion and disease prevention. The
      components of genetic literacy include new views of genetics and of disease, and
      attention to the nature of science, the principles of technology, and ethical,
      legal, and social implications of genetic medicine.

PMID- 12187442
TI  - Redefining the factor structure of the Wechsler Memory Scale-III: confirmatory
      factor analysis with cross-validation.
AB  - The purpose of this study was to revisit the underlying factor structure of the
      Wechsler Memory Scale-III. The WMS-III Technical Manual (Wechsler, 1997)
      presented findings from confirmatory factor analyses that support a three- and
      five-factor solution with separate immediate and delayed memory factors. A
      rigorous structural equation modeling approach was used to examine the factor
      structure of the test. The results verify that a three-factor model composed of
      verbal (immediate and delayed), visual (immediate and delayed), and working
      memory factors accurately represents the factor structure of the WMS-III. Results
      were cross-validated on an independent sample.

PMID- 12187441
TI  - The Rey 15-item recognition trial: a technique to enhance sensitivity of the Rey
      15-item memorization test.
AB  - Numerous publications on the Rey 15-item Memorization Test have cited limitations
      primarily in test sensitivity, as well as to some extent in specificity. In the
      current study, 49 patients with suspect effort, 36 neuropsychology clinic
      patients not in litigation or attempting to secure disability, 33 learning
      disabled college students, and 60 normal controls were administered the Rey Test
      in standard format followed by a recognition trial. A free recall score <9 was
      found to have excellent specificity (97-100%), although sensitivity was modest
      (47%). However, use of a combined recall and recognition score (i.e., free recall
      + [recognition - false positives] <20) substantially increased sensitivity (71%)
      while maintaining high specificity (> or=92%).

PMID- 12187443
TI  - The Tower of London spatial problem-solving task: enhancing clinical and research
      implementation.
AB  - Since its development in 1982, The Tower of London (TOL; Shallice, 1982) spatial
      problem-solving task has been increasingly employed in test batteries of
      executive functions. This task has served as a rich source of information on
      preparation, planning and processing, but a number of issues remain unaddressed
      in the literature: (1) the problem structure, or problem space of the task, (2)
      the impact of modifications from the original, Shallice TOL, and (3) the variety
      of performance measures that can be derived from the TOL. We present here an
      overview of these issues in the hope that it may lead to a more effective and
      reasoned use of the TOL task by clinical and nonclinical investigators, alike.

PMID- 12187444
TI  - On the reliability of laterality effects in a dichotic emotion recognition task.
AB  - The present study examined the reliability of a dichotic emotion recognition task
      under three different conditions presumed to provide different levels of control
      of attention deployment. Sixty right-handed undergraduate students were randomly
      assigned to one of the three conditions. The task involved dichotic presentation
      of words pronounced in an angry, happy, sad, or neutral, emotional tone. The free
      recall condition applied no attention control. It required participants to report
      the emotion heard in each ear. Both the monitoring and ABX conditions presumably
      forced participants to divide their attention equally between the ears. In
      monitoring, participants were required to indicate when a target emotion was
      presented to either ear. Finally, the ABX condition required participants to
      indicate whether the emotional tone of a binaural stimulus matched either of the
      dichotic stimuli on the same trial. Results showed the expected left ear
      advantage (LEA). In addition, the monitoring and ABX procedures were found to be
      somewhat more reliable than the free recall procedure. The present study suggests
      that control of attention deployment strategies is critical in the reliable
      assessment of laterality. Issues related to task difficulty and its effect on the
      reliability and magnitude of laterality effects are also discussed.

PMID- 12187445
TI  - Normative data for neuropsychological measures of fluency, attention, and memory
      measures for Hong Kong Chinese.
AB  - Normative information on neuropsychological measures for Chinese people is
      scarce. This study addresses this inadequacy by providing norms on several tests,
      using a sample of 475 Cantonese-speaking Chinese aged from 13 to 46. Included are
      eight neuropsychological measures of attention, memory, and fluency, which
      provided an overview of some important neuropsychological functions along the
      verbal-nonverbal axis. Age, gender, and education were factors observed to have
      an effect on the test performance of these participants. This pattern is
      consistent with that reported in Western literature. These measures appear to be
      appropriate clinical instruments for use in Hong Kong Chinese society, although
      the usefulness of the current norms is limited to adolescents and, to a lesser
      extent, to young adults in that population. Also, because of possibly important
      differences in the linguistic and educational backgrounds of Hong Kong residents
      versus Chinese residents of other countries (including mainland China and North
      America), applicability of the current norms outside of Hong Kong is currently
      uncertain.

PMID- 12187446
TI  - The functional locus of intrusions: encoding or retrieval?
AB  - Many current accounts of the origin of intrusions and other confabulatory-like
      phenomena emphasize the role of a retrieval or postretrieval deficit in these
      disorders. In the experiments reported herein we examine whether the presence of
      an interfering task at encoding elicits more intrusions in normal subjects than
      the presence of an interfering task at retrieval. In Experiment 1, performance in
      story recall without interference was compared to the performance with an
      interfering task at retrieval. In Experiment 2, the performance in story recall
      with an interfering task at encoding was compared to performance in story recall
      with interference at encoding and retrieval. Results suggest that interference at
      retrieval has no effect on the accuracy of recall and on intrusions. Interference
      at encoding compared to interference at encoding and retrieval (Experiment 2) had
      no effect on the accuracy of recall and on frequency of intrusions. Cross
      experiment comparisons suggest that interference at encoding affects both the
      accuracy of retrieval and the probability of intrusions in recall. These results
      suggest that encoding processes, more than retrieval processes, have a role in
      eliciting intrusions.

PMID- 12187447
TI  - Adult age differences in strategy use during verbal fluency performance.
AB  - This study investigated adult age differences in strategy use during verbal
      fluency performance among 60 older and 60 younger adults. Clustering and
      switching, strategic components of fluency, were investigated as predictors of
      performance along with cognitive processes thought to underlie these strategies,
      namely verbal ability, speed of processing and executive function (strategic
      planning, performance monitoring, etc.). Two measures of verbal fluency were
      used: initial and excluded letter (words produced not containing a designated
      letter). These tasks both require search for words based on a phonemic cue but
      are thought to reflect a differential reliance on strategic retrieval search
      processes for successful performance. The number of clusters produced accounted
      for age differences in excluded, but not initial, letter fluency. Performance on
      both fluency tasks was associated with the number of clusters and switches
      participants produced and initial letter fluency was associated with cluster size
      for older adults and a ratio index of effective search for both age groups. In
      general, both fluency tasks relied on verbal ability and articulation speed, and
      excluded letter fluency performance relied more on speed and executive function
      than did initial letter fluency, especially for older adults.

PMID- 12187448
TI  - Motor and cognitive sequelae of unilateral pallidotomy in intractable Parkinson's
      Disease: electronic measurement of motor steadiness is a useful outcome measure.
AB  - This study examined the short-term motor and cognitive sequelae of unilateral
      posterolateral pallidotomy for patients with intractable Parkinson's Disease
      (PD). Unique to this study was the inclusion of electronic motor steadiness
      instrumentation among pre- and postsurgical assessment procedures. Fifteen PD
      patients underwent right-sided surgery and 10 underwent left-sided surgery;
      patients were evaluated 1 month presurgery and approximately 3 months
      postsurgery. Motorically, there were no significant changes in grooved pegboard
      or maze-drawing performances, but patients evidenced significantly improved
      steadiness, particularly in the hand contralateral to the side of surgery.
      Cognitively, there were no significant decrements on postsurgery composite
      variables comprised of well-known tests of attention, executive functioning,
      delayed memory or recognition memory; these findings were similar for patients
      with either left- or right-sided surgery. There was, however, a significant
      change in language abilities among a subset of patients. This change was evident
      in the decline in verbal fluency in PD patients who underwent left-sided
      pallidotomy, a finding that has consistently emerged in pallidotomy outcome
      studies. This decline is discussed in terms of evidence that suggests that the
      basal ganglia consist of several separate, but parallel circuits, some of which
      are important for cognition.

PMID- 12187449
TI  - The role of functional MRI in the presurgical investigation of temporal lobe
      epilepsy patients: a clinical perspective and review.
AB  - Speculation regarding the role that fMRI might play in the presurgical assessment
      of temporal lobe epilepsy patients began almost as soon as the technology was
      introduced. Much of this speculation centred on hopes that fMRI might eventually
      supersede the invasive intracarotid amobarbital procedure (IAP). This review
      examines the progress that has been made to date towards this aim. A decade after
      its inception, fMRI paradigms that reliably lateralize language dominance have
      been established. However, fMRI has yet to achieve its full potential in the
      mapping of clinically relevant language skills in presurgical epilepsy patients.
      The role of fMRI in the assessment of postoperative amnesic risk is more complex.
      The results from recent fMRI memory studies in people with epilepsy have been
      encouraging. However, as yet, fMRI techniques cannot be used alone to confidently
      assess the risk of a postsurgical amnesic syndrome. It seems probable that these
      techniques will continue to be combined with traditional neuropsychological
      assessment and information from structural MRI studies and the other presurgical
      investigations to assess postoperative amnesic risk.

PMID- 12187450
TI  - Neuropsychological test performance of patients with Friedreich's ataxia.
AB  - Although recognized as one of the most common hereditary diseases of the nervous
      system, the neuropsychological deficits in Friedreich's ataxia (FA) have rarely
      been studied. A protocol was constructed to assess the major cognitive areas in
      patients with FA and pair-matched normal controls. Motor difficulties, dysarthria
      and fatigability were taken into account. Neuropsychological assessment showed
      decreased motor and mental reaction times, reduced verbal span, deficits in
      letter fluency, impaired acquisition and consolidation of verbal information,
      proactive interference effect, and alterations in complex visuoperceptual and
      visuoconstructive abilities, in comparison with the control group. Magnetic
      resonance images showing cerebellar atrophy in the majority of patients suggest
      that cerebellar degeneration and the interruption of afferent and efferent
      cerebellar connections could be related to the cognitive deficits shown by our
      patients.

PMID- 12187451
TI  - Serial position learning effects in patients with aneurysms of the anterior
      communicating artery.
AB  - Ruptured and repaired Anterior Communicating Artery (ACoA) aneurysm can result in
      devastating impairments involving memory, executive function, confabulation, and
      personality changes. This study tested serial position learning effects (SPEs) in
      patients following repaired and ruptured ACoA aneurysm, using results on the Rey
      Auditory Verbal Learning Test (RAVLT). Thirty patients with ruptured aneurysms of
      the ACoA and 31 matched controls were included in the study. The primacy-recency
      effects were maintained during five learning trials in ACoA group, albeit at an
      overall lower level than in the controls. There was no difference in primacy
      recency relation across five learning trials in ACoA group. On the delayed recall
      trial the patient group demonstrated neither a primacy, nor a recency phenomenon,
      reflecting a lack of recall of any parts of the word list. This kind of primacy
      recency profile across learning trials in ACoA group has no similarity with SPE
      results in frontal lesion groups, or with SPE distributions in other amnesic
      disorders, despite the fact that memory and executive deficits were evident in
      our ACoA group.

PMID- 12187452
TI  - Talking while performing a task: a better attentional performance in patients
      with closed head injury?
AB  - This study explored the potentially beneficial effect of explicit verbalization
      on the attentional performance in patients with closed head injury (CHI) in both
      distracting and nondistracting environments. Ten patients with CHI and 10 normal
      controls were recruited. The findings indicated that in the absence of
      distractors, the two groups did not differ significantly on the total actual time
      of off-task behaviour. When distractors were present, the patients performed
      worse than their controls; whereas verbalization tended to reduce total actual
      time of off-task behaviour in patients more than normal controls (z=1.965,
      p=.049), the controls were at ceiling under the verbalization condition. Although
      the findings must be considered tentative because of this ceiling effect and the
      small sample sizes, our results do suggest that patients with CHI benefit more
      from self-instructional cues in a complex and distracting environment.

PMID- 12187453
TI  - Brief report: anosmia and remote outcome in closed head injury.
AB  - The value of posttraumatic anosmia as a predictor of late social outcomes was
      examined in a sample of closed head injury (CHI) patients. Unemployment rates
      were equally high in both the anosmic and nonanosmic closed head injury patients.
      The groups also did not differ in psychiatric or neuropsychological status.
      Anosmic patients had longer initial hospital stays and deeper initial
      comatose/confusional states. Anosmia does not appear to add incrementally to
      disability status and it does not automatically imply the presence of basal
      frontal damage.

PMID- 12187455
TI  - A rapid screen of the severity of mild traumatic brain injury.
AB  - This study investigated the sensitivity of information processing, recall and
      orientation tasks to the presence of mild Traumatic Brain Injury (mTBI). Fifty
      six (40 male, 16 female) mTBI patients and 85 (57 male and 28 female) controls
      with orthopaedic injuries were tested within 24 hr of injury in the Department of
      Emergency Medicine. mTBI patients answered fewer orientation questions and
      recalled fewer words in delayed recall than orthopaedic patients. mTBI patients
      judged fewer sentences in 2 min than orthopaedic controls, and female mTBI
      patients judged fewer sentences than male mTBI patients. Male mTBI patients
      correctly recalled fewer words during immediate memory and learning than female
      mTBI patients and orthopaedic controls. Those mTBI patients with a history of
      previous head injuries did not perform more poorly than those mTBI patients
      without previous head injuries. These results indicate that tests of speed of
      information processing, word learning and orientation questions are sensitive to
      the acute effects of mTBI.

PMID- 12187456
TI  - Significant other burden and factors related to it in traumatic brain injury.
AB  - Feelings of burden and factors related to it were examined in a sample of 180
      relatives of moderately to severely traumatically brain injured (TBI) subjects 6
      months postinjury. Relatives were enrolled onto the study based on their family
      member's head injury and not on outcome. The results indicate that although both
      positive and negative experiences were common, the majority of the relatives
      reported an overall positive experience. The significant other's (SO's)
      experience was significantly and systematically related to many factors with
      overall negative experience associated with increased brain injury severity,
      worse neuropsychological functioning, increased dependency on others, SO's report
      of changes in the TBI subject, changes in the SO's life as a result of caregiving
      and SO depression.

PMID- 12187457
TI  - Caregiver burden during the year following severe traumatic brain injury.
AB  - Fifty-two primary caregivers of people with a severe traumatic brain injury (TBI)
      were assessed at 6-months and 1-year postinjury. Caregiver appraisal of the
      person with TBI's physical, cognitive, emotional, behavioural, and social
      functioning was assessed. Caregiver psychosocial functioning and levels of
      subjective and objective burden were also assessed. Some aspects of the
      difficulties reported for the people with TBI remained stable, while others
      increased in frequency, over time. At 6-months postinjury, approximately one
      third of caregivers reported clinically significant symptoms of anxiety and
      depression, and poor social adjustment. By 1-year postinjury, the prevalence of
      anxiety and depression remained the same, although only one-quarter continued to
      report poor social adjustment. There was some evidence of adaptation by
      caregivers, as the frequency with which various types of objective burden were
      reported remained stable, while the distress caused by these decreased in the
      first year postinjury. It appears that the impact on caregivers of physical
      impairment is comparatively short-lived and that caregivers learn some practical
      ways to manage the behavioural problems of the people with TBI. Despite this,
      over time the person with TBI's behavioural and cognitive problems begins to play
      a larger role in the level of distress experienced by the caregiver. However, it
      is the person with TBI's social isolation that has a stable and consistent role
      in the experience of subjective burden for primary caregivers in the first year
      postinjury.

PMID- 12187458
TI  - "Diagnosis Threat": the effect of negative expectations on cognitive performance
      in head injury.
AB  - The present study examined the effect of negative expectations on
      neuropsychological test performance. It was hypothesized that having attention
      called to a history of prior head injury and the potential effects of head injury
      on cognition would result in diminished neuropsychological test performance
      relative to individuals with a similar head injury history but who did not have
      their attention called to their head injury history ('diagnosis threat'). Of 36
      participants with a history of mild head injury, 17 were randomly assigned to
      diagnosis threat and 19 to neutral test directions. The diagnosis threat group
      performed significantly worse on tests measuring general intellect and memory,
      but were not different from the neutral group in basic attention or psychomotor
      speed. The diagnosis threat group rated themselves as putting forth less effort
      on the neuropsychological battery, and self-rated effort correlated with test
      performance in that group. Overall, results serve as a reminder that
      neuropsychological tests are measures of behavior, and thus can be influenced by
      nonneurological factors.

PMID- 12187459
TI  - Pediatric traumatic brain injury and procedural memory.
AB  - This study investigated the effects of pediatric Traumatic brain injury (TBI) on
      procedural memory. Fifteen children with moderate to severe TBI and 15 matched
      controls were compared on two procedural-memory tasks: motor-perceptual (rotary
      pursuit) and cognitive (mirror reading). Explicit-memory tasks were also
      completed: recall or recognition of rotary-pursuit items and mirror-reading
      words. On both procedural tasks, the TBI group learned at a similar rate and
      retained equally well as the controls. On the explicit-memory tasks, however, the
      TBI group recalled and recognized fewer test items than the controls. These
      results are consistent with those reported in the adult TBI literature and
      suggest that procedural memory, a type of implicit memory, is preserved in
      children with TBI. Implications of these findings for the management and
      rehabilitation of children with TBI were discussed.

PMID- 12187460
TI  - The influence of "State" related factors on focused attention following whiplash
      associated disorder.
AB  - The modified Stroop task was presented to 48 patients with a Whiplash Associated
      Disorder (WAD) and 48 healthy matched controls to investigate possible
      attentional impairments in relation to state related factors (headache, neck
      pain, fatigue, tension and state-anxiety). It was expected that performance on
      the Stroop task is negatively influenced by these state related variables.
      Confirming the expectations, the results showed that response latencies increase
      for Subtasks 1 through 4, for both groups. In addition, WAD patients performed
      significantly worse on all subtasks. There was a significant interaction between
      the two groups and the four subtasks. The results revealed signs for interference
      susceptibility or reduced capacity to shift attention on the modified Stroop
      task. The results concerning the influence of state variables indicated that the
      intensity of headache was significantly related (demonstrating a worsening) to
      Stroop task performance in the WAD-group. It was concluded that WAD patients
      exhibit a general slowing of information processing, especially on tasks that
      require controlled attention. There are signs for subtle deficits in focused
      attention. The intensity of headache seems to play an important influence on
      attentional functioning. Clinical implications are discussed.

PMID- 12187461
TI  - Initial rightward orienting bias in clinical tasks: normal subjects and right
      hemispheric stroke patients with and without neglect.
AB  - In order to develop the diagnosis of hemi-inattention in patients with right
      hemispheric cerebrovascular accident (RCVA), the initial starting point of
      cancellation performance was studied in seven commonly used visual cancellation
      tasks, an Object Finding task, and a blindfold Tactuo-motor search task. The
      subject groups consisted of 34 patients with RCVA and 31 healthy subjects.
      Patients were divided into groups of contralateral neglect and no neglect. One
      additional case of ipsilesional neglect and one of nonlateralised attentional
      disorder in relation to early orienting bias, are reported. Patients with
      contralateral neglect showed a strong tendency to start their cancellation
      performance on the right. Also, half of the nonneglect patient group demonstrated
      right bias in initiating their cancellation performance, suggesting the presence
      of a subclinical hemi-inattention group. Contrary to expectations, also a small
      proportion of normal subjects were right-biased. Task dependent differences in
      the assessment of early rightward orienting bias were found.

PMID- 12187462
TI  - Factor structure, normative data and retest-reliability of a test of fine motor
      functions in patients with idiopathic Parkinson's disease.
AB  - The purpose of this study was to measure the stability of motor functions in
      patients with idiopathic Parkinson's disease (IPD). A test of fine motor skills
      was developed that allow objective repeated measures of momentary capability
      among this group of patients. The study included 114 right-handed IPD-patients
      (mean age: 67.0+/-9.4 years, mean duration of the disease: 6.1+/-4.9 years).
      Patients with dementia, pharmacogenic psychiatric side-effects, other
      neurological diseases and tremor-type IPD were excluded. All patients were tested
      with an apparative motor performance test ('Motorische Leistungsserie nach
      Schoppe') and 24 hr later, again with the identical test. The patients (all
      properly adjusted to medication) were receiving different drug combinations;
      there was no change in the medication between tests for patients included in the
      analysis. Seven factors were extracted: 'finger-tapping speed,' 'speeded manual
      dexterity,' 'speeded finger dexterity,' 'movement planning,' 'complex movement:
      right,' 'complex movement: left,' and 'steadiness.' The subtests proved to have
      acceptable test-retest reliability. It is thus possible to produce objective,
      statistically sound data which enable a confirmation of improvement via
      medication or of the illness' progression. The presentation of normative data
      permits intra- and inter-individual interpretations of a single patient's
      performance. In addition, the patients' performance can also be compared with
      that of healthy controls in similar age groups (cf. data in the literature).

PMID- 12187463
TI  - Inhibitory breakdown and dementia of the Alzheimer type: a general phenomenon?
AB  - Several recent studies have provided substantial support for the proposal that a
      decrease in inhibitory processing may play an important role in cognitive changes
      occurring in the early stages of Dementia of the Alzheimer Type (DAT). The
      question addressed by the present study was whether these deficits are the result
      of the failure of a general inhibitory mechanism, or whether DAT is associated
      with selective decreases in a subset of inhibitory processes. For this, a
      computerized battery of tasks assessing several inhibitory mechanisms was
      administered to 28 mild DAT patients and 28 matched elderly adults. The results
      showed that DAT patients failed to produce Negative Priming effects and were
      severely impaired in the Stroop task. However, no evidence was found for an
      impairment on the Go-No go task and only limited impairment on the Stop Signal
      task, suggesting that in the early stages of the disease, not all inhibitory
      mechanisms are uniformly impaired.

PMID- 12187464
TI  - Disturbance of "extrinsic alertness" in Huntington's disease.
AB  - Neuropsychological deficits are a main feature of Huntington's disease (HD) with
      previous data suggesting involvement of attentional functions. Attention can be
      divided into several different dimensions: intensity, selectivity and supervisory
      attentional control. These different aspects of attention were investigated in a
      group of 13 patients with HD and 13 healthy matched control subjects. HD patients
      were impaired mostly for the intensity dimension: contrary to controls, and like
      other neurological patient groups, they were not able to speed up their reaction
      times when an auditory warning stimulus preceded a visual target which suggests a
      deficit in 'extrinsic alertness.' In addition less severe impairments were found
      in the dimensions selectivity and supervisory attentional control.

PMID- 12187465
TI  - Neuropsychological functioning and its relationship to antiphospholipid
      antibodies in patients with systemic lupus erythematosus.
AB  - While it is clear that central nervous system (CNS) lesions in systemic lupus
      erythematosus (SLE) adversely affect cognitive functioning, it is also evident
      that patients without visible lesions (non-CNS SLE) may also exhibit subtle
      cognitive impairment. The presence of antiphospholipid antibodies (aPLs) has been
      proposed as a marker of disease severity and hence should be correlated with
      neuropsychological dysfunction in this population. The current study compared
      groups of non-CNS lupus patients who were positive (LA+) or negative (LA-) for
      aPLs on selected measures of neuropsychological functioning. In addition, we
      attempted to characterize the pattern of cognitive impairment that is associated
      with LA status in these patients. No coherent neuropsychological pattern emerged,
      but LA+ patients performed worse than LA- patients on measures assessing
      attention, concentration, and visual search, as well as spatial learning and
      memory.

PMID- 12187466
TI  - Putative tests of frontal lobe function: a PET-study of brain activation during
      Stroop's Test and verbal fluency.
AB  - Stroop's test and the Verbal Fluency test are commonly argued to be measures of
      the integrity of the prefrontal cortex. This assumption has only to some degree
      been confirmed by lesion studies. In the present study, Positron Emission
      Tomography (PET) with H(2)(15)O was used to further validate Stroop's test and
      the Verbal Fluency as measures of frontal lobe function; both tests were
      implemented as activation paradigms during scanning of normal middleaged
      individuals. Stroop interference was found to activate the left anterior
      cingulate cortex, the supplementary motor cortex, thalamus, and the cerebellum.
      Although the prominent anterior cingulate activation is in the frontal lobe, it
      is not prefrontal. Verbal Fluency activated the left inferior frontal cortex and
      the left dorsolateral prefrontal cortex, the supplementary motor cortex, the
      anterior cingulate cortex and the cerebellum. These results bring this latter
      test closer to being a specific test of prefrontal function.

PMID- 12187467
TI  - I cannot remember, but I know my past events: remembering and knowing in a
      patient with amnesic syndrome.
AB  - Case Y.K. has severe anterograde amnesia and a selective loss of specific
      personal episodes in his remote memories (Hirano & Noguchi, 1998). In this paper,
      we attempted to analyze remembering (R) and knowing (K) responses, that is, the
      relationship between autobiographical remembering and remembering accompanied by
      subjective experience. Although the rate of R responses was significantly higher
      than that of K responses in control subjects, Y.K.'s R responses were rare in all
      subtypes of remote memories. Based on these results, we conclude that Y.K.'s
      memories on autobiographical incident task were not based on episodic memory but
      rather on semantic memory. Thus, the autobiographical incidents he could recall
      were not episodic memory, and his semantic memory made him recall information as
      fact rather than episode.

PMID- 12187470
TI  - The development of specialized brain systems in reading and oral-language.
AB  - Functional magnetic resonance imaging (fMRI) was used to examine differences
      between children (9-12 years) and adults (21-31 years) in the distribution of
      brain activation during word processing. Orthographic, phonologic, semantic and
      syntactic tasks were used in both the auditory and visual modalities. Our two
      principal results were consistent with the hypothesis that development is
      characterized by increasing specialization. Our first analysis compared
      activation in children versus adults separately for each modality. Adults showed
      more activation than children in the unimodal visual areas of middle temporal
      gyrus and fusiform gyrus for processing written word forms and in the unimodal
      auditory areas of superior temporal gyrus for processing spoken word forms.
      Children showed more activation than adults for written word forms in posterior
      heteromodal regions (Wernicke's area), presumably for the integration of
      orthographic and phonologic word forms. Our second analysis compared activation
      in the visual versus auditory modality separately for children and adults.
      Children showed primarily overlap of activation in brain regions for the visual
      and auditory tasks. Adults showed selective activation in the unimodal auditory
      areas of superior temporal gyrus when processing spoken word forms and selective
      activation in the unimodal visual areas of middle temporal gyrus and fusiform
      gyrus when processing written word forms.

PMID- 12187471
TI  - Verbal fluency deficits in children with specific language impairment: slow rapid
      naming or slow to name?
AB  - This study examined aspects of verbal fluency performance of children with
      Specific Language Impairment (SLI) and typically developing children matched on
      age and Block Design scores. While children with SLI showed deficits in verbal
      fluency compared to their peers, they showed the same pattern of performance on
      phonemic compared to semantic fluency trials. Children with SLI and normally
      developing children also demonstrated equivalent rates of clustering and
      switching, measures hypothesized to reflect aspects of frontal lobe functioning,
      when the overall number of exemplars was taken into account. The absence of a
      condition by group effect supports general processing limitation accounts of SLI,
      while the absence of group differences on cluster size and switches supports
      language-based processing accounts of SLI.

PMID- 12187472
TI  - Concurrent verbal and emotion laterality effects exhibited by normally achieving
      and learning disabled children.
AB  - This study assessed both left- and right-hemisphere functions simultaneously when
      two-syllable words differing only in the initial stop consonant and spoken in
      different emotional tones were paired dichotically. Seventy-two right-handed
      normally achieving children, 12 boys and 12 girls at each of grades 1, 3, and 5,
      were instructed to detect either the presence of a specific word or of a specific
      emotion. In addition, 30 right-handed learning disabled (LD) children (age
      matched to the normal controls) were assessed to determine whether LD children
      distribute verbal and nonverbal functions to different hemispheres. Results
      indicated that although both control and LD children demonstrated an overall REA
      for word stimuli and an LEA for emotional stimuli, and that emotional stimuli
      were easier to process than word stimuli, LD children were less accurate in
      processing both types of stimuli than their control counterparts. 'Complementary
      specialization,' as assessed through distribution of laterality effects, was
      found to be greater for control children than for LD children. However, the lack
      of consistency in complementary specialization found among the three
      developmental grade levels may be indicative that independent brain mechanisms
      underlying verbal and emotional processing have yet to be fully established in
      children. Further, in contrast to adult findings, a larger LEA was obtained for
      the emotion 'happy' than for the emotion 'sad.' It was concluded that whereas
      independent hemisphere processing for words and emotions is somewhat prevalent
      for control children, LD children might not be as strongly lateralized for
      opposite hemisphere processing of these functions.

PMID- 12187473
TI  - An investigation of prospective memory in children with ADHD.
AB  - Prospective memory, defined as the ability to follow through on intended
      behavior, is believed to be subserved by a number of neuroanatomical substrates,
      but particularly dependent, at least in part, on the frontal lobes. Children with
      Attention-Deficit Hyperactivity Disorder (ADHD) traditionally have difficulty on
      tasks dependent on frontal lobe structures. The present study attempted to
      determine whether children with ADHD are impaired in prospective memory function.
      Two studies are described that use a new measure of time-based prospective
      memory, the CyberCruiser (Kerns, 2000), to compare children with ADHD to a
      control group consisting of participants who were matched in respect to age,
      gender, and IQ. The results document prospective memory deficits in ADHD.
      Prospective memory performance correlated significantly with clinical measures of
      ADHD as assessed by the Conners' Parent Rating Scale (Conners, 1990)
      Hyperactivity Index, but was unrelated to intellectual ability. Though
      psychometric measures of attention correlated with prospective memory
      performance, they did not account for the differences in prospective memory that
      were observed between the ADHD and control groups.

PMID- 12187474
TI  - Response inhibition in children with DSM-IV subtypes of AD/HD and related
      disruptive disorders: the role of reward.
AB  - The current study had four aims: (a) to replicate previous findings of slow
      response inhibition in Attention Deficit/Hyperactivity Disorder (AD/HD), (b) to
      explore whether poor response inhibition in children with AD/HD is a core problem
      or rather a result of an underlying problem related to reward, (c) to investigate
      the specificity of poor response inhibition and the role of reward in relation to
      AD/HD, and (d) to study whether findings would be different for three subtypes of
      AD/HD. In order to address these issues, a stop paradigm was administered under a
      reward condition and under a nonreward condition to an AD/HD group (n=24), an
      Oppositional Defiant Disorder (ODD)/Conduct Disorder (CD) group (n=21), a
      comorbid AD/HD+ODD/CD group (n=27), and a normal control (NC) group (n=41).
      Firstly, contrary to prediction, none of the Disruptive Behavior Disorder (DBD)
      groups differed from the NC group with respect to the speed of the inhibition
      process. Secondly, it was shown that children with AD/HD and children with
      comorbid AD/HD+ODD/CD, but not children with ODD/CD alone, slowed down more
      dramatically in the reward condition than normal controls. This finding was
      interpreted as a strategy to increase the chance of being rewarded in children
      with AD/HD and children with comorbid AD/HD+ODD/CD, but not in children with pure
      ODD/CD. Finally, analysis of AD/HD subtypes did not change the main findings of
      this study.

PMID- 12187475
TI  - Test of everyday attention for children.

PMID- 12187477
TI  - The relationship between age and intraocular pressure in a Japanese population:
      the influence of central corneal thickness.
AB  - PURPOSE: Previous cross-sectional Japanese studies have shown that intraocular
      pressure (IOP) decreases with age. However, central corneal thickness (CCT)
      variation should also be considered when examining the relationship between age
      and IOP, since tonometry has an inherent measurement error due to CCT variations.
      This study investigates the influence of CCT variation on the age-IOP
      relationship in a Japanese population. METHODS: The right eyes of 1317 subjects
      from 40 to 80 years old selected from a general population using a random
      sampling method were assessed in cross-section. The IOP was measured with a non
      contact tonometer, and CCT was measured with a specular microscope. The
      relationships between age, IOP, and CCT were assessed using correlation analyses,
      while the relationship between age and IOP controlled for CCT, blood pressure,
      and body mass index was investigated using multivariate regression analyses.
      RESULTS: The mean (+/- SD) IOP value was 13.6 (+/- 2.6) mmHg in men and 13.3 (+/-
      2.6) mmHg in women. The IOP correlated inversely with age in men (r = -0.14, p <
      0.001), but showed only a marginal inverse correlation in women (r = -0.07, p =
      0.066). The mean (+/- SD) CCT value was 518.3 (+/- 33.2) microm in men and 511.1
      (+/- 33.0) microm in women. Only in men was an inverse correlation seen between
      CCT and age (r = -0.10, p = 0.009), but both genders had positive correlations
      between CCT and IOP (man: r = 0.44, p < 0.001; woman: r = 0.48, p < 0.001). In
      multivariate analyses, CCT was shown to have an effect on IOP measurement,
      however, it was shown that IOP still decreases with age in both sexes even when
      adjusted for CCT (p = 0.001). CONCLUSIONS: The IOP decreases with age in the
      Japanese, and CCT variation has practically no effect on the unique age-IOP
      relationship.

PMID- 12187479
TI  - Characterization of T lymphocyte subtypes in endotoxin-induced uveitis and effect
      of pentoxifylline treatment.
AB  - PURPOSE: The aims of the study were twofold: 1) to investigate the role of T
      lymphocyte subtypes in the pathogenesis of endotoxin-induced uveitis (EIU) and 2)
      to study the possible beneficial effect of pentoxifylline, an inhibitor of
      neutrophil motility, and Tumor Necrosis Factor-alpha on this disease. METHODS:
      Forty-two inbred male Lewis rats were divided into seven equal groups. 200 microg
      of Escherichia coli 055: B55 lipopolysaccharide (LPS) was injected in one hind
      footpad of the Group 2, 3, 4, 5, 6, and 7 rats. Group 5, 6, and 7 rats also
      received concomitant intraperitoneal pentoxifylline (PTX) during food pad
      injection of LPS. Group 1 rats were used as controls with intra-peritoneal normal
      saline injection. Eight, 24, and 48 hours after treatment, the rats were
      euthanized. Neutrophil leukocyte, mononuclear cells, and CD4+, CD8+, and CD45RA+
      cell infiltration in the anterior uveal tissue were determined either by
      hematoxylin-eosin or monoclonal antibody staining. Tumor Necrosis Factor-alpha
      (TNF-alpha) levels were also measured in the aqueous and blood samples. We
      compared the numbers of infiltrating cells in the different groups. RESULTS: We
      found that peak infiltration of lymphocyte, neutrophils, and CD4+ cells occurred
      at 24 hours. However, CD8+ and CD45RA+ cell number reached their highest levels
      at 48 hours. There was no inflammatory cell infiltration in the control rats.
      Concomitant pentoxifylline treatment did not affect any of these parameters,
      although it effectively reduced TNF-alpha concentrations in the anterior chamber
      and the serum. CONCLUSION: We conclude that, 1) T lymphocytes might be involved
      in the pathogenesis of endotoxin-induced uveitis. 2) The potential role of
      pentoxifylline in the treatment of human uveitis is questionable. However, these
      are initial findings and need confirmation by additional studies.

PMID- 12187478
TI  - The effect of prinomastat (AG3340), a synthetic inhibitor of matrix
      metalloproteinases, on uveal melanoma rabbit model.
AB  - PURPOSE: We studied the effects of intravitreally administered prinomastat on the
      take rate and growth of uveal melanoma after xenograft implantation in rabbit
      uveal melanoma model. METHODS: Uveal melanoma xenograft was implanted to
      suprachoroidal space in each eye of 24 pigmented rabbits which were
      immunosuppressed with cyclosporine. One week after surgery, the eyes were
      randomized to receive prinomastat or the vehicle of the prinomastat
      intravitreally every week for 4 weeks. The take rate of the xenograft, tumor
      height, apoptosis, and necrosis in the eyes which developed tumors from the
      treatment and control groups were compared. RESULTS: A tumor mass was identified
      in 8 of 24 (33%) prinomastat-treated eyes and 20 of 24 (83%) of the vehicle
      treated eyes. Echographic measurements revealed a mean tumor height of 2.2 mm in
      the prinomastat-treated group and 3.8 mm in the control group in those eyes with
      take of tumor (p < 0.001). Stereomicroscopic measurements showed a mean tumor
      height of 1.9 mm in the treatment group and 3.9 mm in the control group (p <
      0.001). The mean number of apoptotic nuclei detected per mm(2) of the histologic
      section in the non-necrotic tumor was 8.12 in the prinomastat-treated group and
      0.57 in the control group (p < 0.001). Evaluation of the digital images in
      microscopic sections of the tumors on histologic slides revealed 29.6% necrosis
      in prinomastat-treated eyes as compared to 10.9% in vehicle-treated eyes (p =
      0.003). CONCLUSIONS: These results suggest that prinomastat treatment
      significantly reduces the take rate and the growth rate of xenograft in uveal
      melanoma rabbit model.

PMID- 12187480
TI  - C1r-C1s-C1inhibitor (C1rs-C1inh) complex measurements in tears of patients before
      and after penetrating keratoplasty.
AB  - PURPOSE: The aim of this pilot study was to determine the presence of complement
      activation products in tears from pre- and postkeratoplasty eyes and the fellow
      eyes in order to investigate the activation of the classical and alternative
      pathways of the complement system in the early postkeratoplasty period. METHODS:
      Tear samples from both eyes of 19 prekeratoplasty patients were tested. From 10
      patients, samples were taken before operation, one week and 3 weeks after
      penetrating keratoplasty. Only baseline and 1 weak samples, and baseline and 3
      week samples were available from 5 and 2 patients, respectively, while only
      baseline tear samples were collected from 2 patients. Tear concentration of two
      complement activation products, C1rs-C1inh and C3bBbP were determined by enzyme
      linked immunosorbent assay. RESULTS: There was no difference (p = 0.339) between
      baseline samples of the eyes waiting for operation (0.93 +/- 0.51 AU/ml, mean +/-
      SEM) and the fellow eyes (0.33 +/- 0.33 AU/ml) in respect of mean C1rs-C1inh
      complex concentration. The one-week samples of the operated eyes revealed
      significantly (p = 0.006) elevated levels of C1rs-C1inh complexes (18.8. +/- 6.37
      AU/ml), compared to their baseline samples (1.18 +/- 0.64 AU/ml), whereas the one
      week values of the fellow eyes did not differ from the baseline values. Compared
      to the increased one-week values, the three-week values decreased to the baseline
      values in the operated eyes. C3bBbP could be detected in 3/68 tear samples.
      CONCLUSIONS: In our study we demonstrated the increased concentration of C1rs
      C1inh complex in several tear samples taken early after human penetrating
      keratoplasty. These findings provide direct evidence that the classical pathway
      of complement may be activated in the early postoperative period after
      penetrating keratoplasty.

PMID- 12187481
TI  - p53 Immunoreactivity, Ki-67 expression, and microcirculation patterns in melanoma
      of the iris, ciliary body, and choroid.
AB  - PURPOSE: The major role of p53 is to modulate cell proliferation, but recently,
      it has been found that p53 also modulates angiogenesis through several pathways.
      Because both cellular proliferation and microcirculation patterns are important
      prognostic markers in uveal melanoma, we tested the relationships between p53
      expression, the expression of the cell proliferation marker Ki-67, and the
      presence of various microcirculation patterns in uveal melanoma. METHODS:
      Immunostaining of p53 and Ki-67 using the bp53.12 and the MIB-1 antibodies,
      respectively, were preformed in 98 uveal melanomas (18 melanomas confined to the
      iris, 30 ciliary body melanomas, and 50 choroidal melanomas). Percent of p53
      positive cells, and the mean MIB-1 positive cell count per high power field were
      calculated in each section by two observers. Microcirculation patterns were
      assessed in adjacent PAS stained sections. RESULTS: p53 immunoreactivity was
      found in 14 of the 98 melanomas. High proliferative activity and epithelioid cell
      type were associated with p53 immunoreactivity. However, p53 immunoreactivity was
      not associated with any of the microcirculation patterns or with tumor location.
      CONCLUSIONS: The findings suggest that alterations in p53 expression are
      associated with the expression of the cellular proliferation marker, Ki-67, but
      are not associated with the presence of microcirculation patterns.

PMID- 12187482
TI  - Influence of diffuse luminance flicker on choroidal and optic nerve head blood
      flow.
AB  - PURPOSE: In the retina there is general agreement that blood flow adapts in
      response to different conditions of light and darkness including diffuse
      luminance flicker. By contrast, regulation of choroidal blood flow in response to
      different light conditions is still a matter of controversy. Thus, we
      investigated the effect of diffuse luminance flicker on choroidal and optic nerve
      head blood flow. METHODS: In a group of 14 healthy volunteers, choroidal blood
      flow and ocular fundus pulsation amplitude were assessed with laser Doppler
      flowmetry and laser interferometry, respectively. Measurements were done before,
      during and after stimulation with diffuse luminance flicker. Furthermore, the
      response of optic nerve head blood flow (ONHBF) to flicker stimulation was
      measured. Flicker stimuli were generated by a Grass PS2 photostimulator,
      stimulating at a frequency of 8 Hz. Flicker light consisted of light flashes at a
      wavelength below 550 nm and produced a retinal irradiance of 140 microW/cm( 2).
      Blood pressure and pulse rate were measured non-invasively. Paired t-test was
      used for statistical analysis. RESULTS: ONHBF increased immediately after onset
      of flicker stimulation. The maximum increase in ONHBF was 30% +/- 10% (mean +/-
      SEM, p < 0.008). Both choroidal perfusion parameters were only slightly increased
      during flicker stimulation, by 2 +/- 2% (laser Doppler flowmetry, p < 0.5) and by
      4 +/- 1% (laser interferometry, p < 0.12). After the end of stimulation all
      values returned to baseline levels. CONCLUSION: Our study clearly demonstrates
      that diffuse luminance flicker increases optic nerve head blood flow. In
      contrast, increased neural activity in the retina has no effect on choroidal
      blood flow. Thus, choroidal blood flow appears to be largely independent of
      alterations in retinal metabolism.

PMID- 12187483
TI  - Neuroprotective effect of nipradilol on axotomized rat retinal ganglion cells.
AB  - PURPOSE: To determine whether nipradilol, a new anti-glaucoma drug, can protect
      retinal ganglion cells (RGCs) from secondary cell death caused by transection of
      the optic nerve (ON). METHODS: The ON was transected 0.7 mm from its exit from
      the eye in Sprague Dawley rats. Nipradilol (1 x 10(-8) - 10(-3) M), timolol,
      prazosin, or sodium nitroprusside (SNP) (1 x 10(-6) - 10(-4) M) was injected
      intravitreally fifteen-minutes before the ON transection. Control eyes received
      the same amount of phosphate buffered (PB). The RGCs were labeled retrogradely by
      placing gelfoam soaked in fluoro-gold (FG) on the stump of ON. RGCs density was
      determined by counting the FG-labeled RGCs in flat-mounted retinas 3 to 14 days
      post-transection. To determine whether the neuroprotective action of nipradilol
      was due to its NO-donor property, carboxy-PTIO, a NO-scavenger, or KT5832, a
      protein kinase G inhibitor, was injected with the nipradilol. RESULTS: After ON
      transection, the number of surviving RGCs after intravitreal injection of 1 x 10(
      4) M nipradilol was significantly higher than that following PB injection. This
      protective activity was dose-dependent. Neither timolol nor prazosin had a
      neuroprotective effect but SNP protected RGCs in a dose-dependent manner. Carboxy
      PTIO and KT5832 decreased the neuroprotective effect of nipradilol. CONCLUSIONS:
      These results indicate that nipradilol has a possibility of neuroprotective
      effect on axotomized RGCs, and the effect depended mainly on its NO-donor
      property.

PMID- 12187484
TI  - Retinal metabolic abnormalities in diabetic mouse: comparison with diabetic rat.
AB  - PURPOSE: Dogs and rats are commonly used to examine the pathogenesis of diabetic
      retinopathy, but mouse is sparingly studied as an animal model of diabetic
      retinopathy. In this study metabolic abnormalities, postulated to contribute to
      the development of retinopathy in diabetes, are investigated in the retina of
      mice diabetic or galactose-fed for 2 months, and are compared to those obtained
      from hyperglycemic rats. METHODS: Diabetes was induced in mice (C57BL/6) and rats
      (Sprague Dawley) by alloxan injection, and experimental galactosemia by feeding
      normal animals diets supplemented with 30% galactose. After 2 months of
      hyperglycemia, levels of lipid peroxides, glutathione, nitric oxides and
      sorbitol, and activities of protein kinase C and (Na-K)-ATPase were measured in
      the retina. RESULTS: Two months of diabetes or experimental galactosemia in mice
      increased retinal oxidative stress, PKC activity and nitric oxides by 40-50% and
      sorbitol levels by 3 folds, and these abnormalities were similar to those
      observed in the retina of rats hyperglycemic for 2 months. CONCLUSIONS: Metabolic
      abnormalities, which are postulated to play important role in the development of
      diabetic retinopathy in other animal models, are present in the retina of
      diabetic mice, and the level of metabolic abnormalities is very comparable
      between mice and rats. Thus, mouse seems to be a promising animal model to study
      the pathogenesis of diabetic retinopathy.

PMID- 12187485
TI  - Transcellular transfer of folate across the retinal pigment epithelium.
AB  - The differential polarized distribution of the folate receptor alpha (FR alpha)
      in the basal membrane and reduced-folate transporter (RFT-1) in the apical
      membrane was demonstrated previously in the retinal pigment epithelium (RPE).
      Based on this, we hypothesized that folate would enter the RPE via FR alpha and
      exit the cell via RFT-1. To test this, we performed in vitro transport assays
      using ARPE-19 cells cultured on permeable supports. The cells were grown for 4
      weeks and electron microscopic analysis indicated that the cells have the
      phenotypic features of normal RPE cells including apical microvillous processes
      and junctional complexes. Measurement of transepithelial resistance showed that
      the resistance increases in the cells as they differentiate over several weeks.
      Transport assays showed that ARPE-19 cells transport folate in a basal-to-apical
      direction, but do not transport this vitamin significantly in the apical-to basal
      direction. This was not a diffusional process, as the paracellular markers inulin
      and sucrose were transferred across the cell monolayer at a much lower level. The
      presence of FR alpha in the basal membrane was demonstrable by folate binding and
      that of RFT-1 in the apical membrane by blockade of folate transport by RFT-1
      specific antibody. This study represents the first in vitro demonstration of
      transcellular transfer of folate across RPE and suggests that folate is
      transported from the choriocapillaris to the adjacent photoreceptor cells in vivo
      by the concerted action of FR alpha in the basal membrane and RFT-1 in the apical
      membrane.

PMID- 12187486
TI  - Characterization and diabetes-induced impairment of nitric oxide synthase in rat
      choroid.
AB  - PURPOSE: To examine the nitric oxide (NO) system in the choroid of normal rats
      and rats with streptozotocin (STZ)-induced diabetes. METHODS: We assayed NO
      synthase (NOS) activity by monitoring the conversion of L-[(14)C] arginine to L
      [(14 )C] citrulline, identified the NOS isoforms by immunoblotting, and examined
      the effects of STZ-induced diabetes on NOS in the rat choroid. RESULTS: Calcium
      independent NOS activity was insignificant in the choroid of normal and diabetic
      rats. Choroidal calcium-dependent NOS activity was high and comparable to that in
      the cerebellum. Neuronal (n) NOS protein in the choroid was found in both the
      membrane and cytosolic fractions and showed similar subcellular distribution as
      NOS activity, while endothelial (e) NOS protein in the choroid was present almost
      solely in the membrane fraction. Total NOS activity (nNOS + eNOS) and protein
      levels of nNOS and eNOS in the choroid were significantly reduced 6 weeks after
      the induction of diabetes. CONCLUSIONS: The high NOS activity in the choroid
      measured in vitro appears to come mostly from nNOS. Because choroidal nNOS exists
      in the parasympathetic perivascular nerve fibers, the decrease in choroidal nNOS
      in diabetic eyes suggests that the choroid undergoes a diabetes-induced neuronal
      disorder. Thus, diabetic choroidopathy encompasses diabetic neuropathy and
      microangiopathy.

PMID- 12187487
TI  - Simultaneous expression of c-Jun and p53 in retinal ganglion cells of adult rat
      retinal slice cultures.
AB  - PURPOSE: To determine whether the apoptosis-associated transcription factor c-Jun
      and the regulator protein p53 are expressed together during retinal ganglion cell
      (RGC) death in slice cultures of adult rat retina, and whether c-Jun expression
      or p53 expression is altered by glutamate. METHODS: Newborn rat RGCs were
      retrogradely labeled by Di-I microinjections into the superior colliculus.
      Retinas were isolated 2 to 4 months later, cut into 200 microm-thick slices.
      These slices were cultured with 0-300 microM glutamate in the presence or absence
      of MK801. Survival was assessed using Sytox green and ethidium homodimer.
      Cultures also were immunostained for Thy-1, c-Jun and/or p53. The linear density
      of stained RGCs was determined by confocal laser microscopy. RESULTS: RGCs in
      freshly-isolated adult retina slices did not express either c-Jun or p53. By 12
      hours in vitro, 12.0 +/- 3.1 cells/mm of RGCs expressed c-Jun and 18.5 +/- 3.5
      cells/mm of RGCs expressed p53 in control cultures. Exposure to glutamate
      increased both c-Jun and p53 positive RGCs in dose-dependent manner, and
      decreased survival in the RGC layer. Following double staining, up to 58% of
      cells in the RGC layer simultaneously expressed both c-Jun and p53. Time-course
      analysis showed that peak c-Jun expression preceded peak p53 expression in
      control and glutamate-treated cultures. CONCLUSIONS: The simultaneous expression
      of both c-Jun and p53 in the cultured adult rat slices raises the possibility
      that each may contribute to the mechanism of RGC death. This is supported by the
      increased p53 and c-Jun inductions in the presence of glutamate.

PMID- 12187488
TI  - Inhibitory effect of bucillamine on laser-induced choroidal neovascularization in
      rats.
AB  - PURPOSE: We investigated the inhibitory effects of bucillamine on formation of
      laser-induced choroidal neovascularization (CNV) in a rat model. METHODS:
      Bucillamine administration (approximately 150 mg/kg/day) was started 1 week
      before photocoagulation and continued to the end of the study. Control groups
      received drinking water. Two weeks after photocoagulation, choroidal
      neovascularization development was evaluated using simultaneous fluorescein and
      indocyanine green angiography, and the maximal thickness of the lesions was
      measured histologically. RESULTS: The incidence of CNV formation was 99.5 +/-
      0.2% [mean +/- standard deviation (SD)] in control rats and 64.3 +/- 15.1% with
      bucillamine (P < 0.01). Histological study showed that the thickness of the CNV
      lesions was 23.4 +/- 6.5 microm (mean +/- SD) in the bucillamine-treated rats,
      which was significantly decreased compared to that in controls (60.8 +/- 9.2
      microm) (P < 0.01). CONCLUSIONS: Our results suggest that bucillamine may inhibit
      the development of laser-induced CNV in rats.

PMID- 12187489
TI  - An immunohistochemical study of endothelin-1 converting enzyme in the human eye.
AB  - PURPOSE: The important role of ET-1 in vasoconstriction has been shown for the
      vasoregulation in the retina, choroid and optic nerve. ET-1 induced vaso
      constriction, however, can be treated effectively at the level of endothelin-1
      converting enzyme (ECE-1) by ECE-1 inhibitors because ECE-1 converts biologically
      almost inactive big endothelin to endothelin-1 (ET-1), the most potent
      vasoconstrictor known. The purpose of this study was to clarify the anatomical
      distribution of ECE-1 in the human eye. METHODS: 11 post-mortem eyes were fixed
      in 4% formalin and embedded in paraffin. 4 microm thin sections were analyzed
      immuno-histochemically using a self-produced monoclonal primary antibody against
      human ECE-1 and a polyclonal alpha-actin antibody for comparison. RESULTS: ECE-1 
      IR was demonstrated in the corneal epithelium, vascular smooth muscle and
      endothelial cells, and in the non-vascular smooth muscle cells of the ciliary
      body, the dilator and sphincter muscle of the iris. CONCLUSIONS: A strong
      immunoreactivity for ECE-1 can be found in the blood vessels of the retina, optic
      nerve and choroid. Therefore, it should be possible to treat ET-1-induced vaso
      constriction in the eye using ECE-1 inhibitors, especially in diseases like
      hypertensive vasculopathy, vasospasm, vaso-occlusions or low tension glaucoma.

PMID- 12187490
TI  - Expression of metallothionein isoforms in human chorioretinal complex.
AB  - PURPOSE: To determine the relative expression of metallothionein isoforms and
      their differential induction by oxidative stress in cultured RPE cells and to
      localize the isoforms in the human chorioretinal complex. METHODS: Total RNA was
      isolated from cultured human retinal pigment epithelial cells using TRI-Reagent.
      An "anchor-oligo-dT primer" was used for the synthesis of cDNA, reverse
      transcribed using avian reverse transcriptase and subsequently subjected to PCR
      analysis using oligonucleotides specific for metallothionein (MT) I, MT II, and
      MT III. The selected transcripts were then used to assess the expression of the
      above elements in fixed tissue sections by in situ hybridization. Cultured RPE
      cells were allowed to phagocytose bovine photoreceptor outer segments (ROS) or
      were treated with H(2)O(2) for 6 hours and then analyzed by RT-PCR or in situ
      hybridization to ascertain the effect of oxidative stress on metallothionein mRNA
      isoform expression. RESULTS: Relative density analysis of amplified products
      demonstrate the presence of MT I, MT II and MT III in RPE cells, with an apparent
      relative expression MT II > MT I > MT III [corrected]. Expression of MT I and MT
      II mRNA was increased by both phagocytosis and hydrogen peroxide, however MT III
      was not induced by either stress. In situ hybridization corroborated the findings
      of the RT-PCR analysis and showed that MTs were mainly localized in the RPE and
      the photoreceptor layer of the retina. CONCLUSIONS: The localization of MT and
      the response of MT to oxidative stress are consistent with a role for MT as an
      antioxidant in the RPE and retina. Studies are ongoing to determine the specific
      mechanisms of action of these antioxidants in RPE cells.

PMID- 12187491
TI  - Ganglion cell responses to retinal light stimulation in the absence of
      photoreceptor outer segments from retinal degenerate rodents.
AB  - PURPOSE: To determine whether a severely degenerated retina without photoreceptor
      outer segments and a non-recordable electroretinogram (ERG) can still show
      retinal ganglion cell (RGC) responses to retinal light stimulation. METHODS: The
      authors measured ERGs and retinal surface RGC responses from six week old rd mice
      and three month old homozygous S334ter line3 rats. Animal eyes were also studied
      by light microscopy, transmission electron microscopy, and immunohistochemistry
      (rats). RESULTS: The corneal ERGs were non-recordable and no photoreceptor outer
      segments were found in either retinal degeneration model. A few cell bodies
      (without outer segments) that were immunoreactive for cone opsin and rhodopsin
      were found in the outer nuclear layer of the rats. Light-driven ON-RGC responses,
      however, were recordable from six week old rd mice. In addition, light-driven ON
      and OFF-RGC responses were recordable from three month old homozygous S334ter
      line 3 rats. CONCLUSIONS: This study suggests that despite the apparent absence
      of photoreceptor outer segments and a non-recordable ERG, ganglion cell responses
      to retinal light stimulation may remain preserved in some severe retinal
      degenerate transgenic rodents.

PMID- 12187492
TI  - Efficacy of Prinomastat) (AG3340), a matrix metalloprotease inhibitor, in
      treatment of retinal neovascularization.
AB  - PURPOSE: To study the activity of the novel anti-angiogenic compound AG3340
      (Prinomastat), a selective inhibitor of matrix metalloproteases, in an animal
      model of retinal neovascularization. METHODS: C57BL/6J mice were used to produce
      oxygen-induced retinal neovascularization. Mice were exposed to room air from
      birth (P0) to postnatal 7 days (P7) and to hyperoxia (75% oxygen) for the next 5
      days. On postnatal day 12 (P12) the animals were returned to the room air and
      were treated until postnatal day 16 (P16) with intraperitoneal injections of AG
      3340. Four groups were assigned: no drug, 1.6 mg/kg/day, 16 mg/kg/day and 48
      mg/kg/day. On day 17 (P17) the animals were sacrificed and the eyes prepared for
      histological sectioning. Preretinal neovascularization was assessed by counting
      neovascular nuclei of endothelial cells in the preretinal side of the internal
      limiting membrane (ILM). The use of animals for this study complies with the ARVO
      guidelines for animal research. RESULTS: AG3340 administered systemically by
      intraperitoneal injections inhibited hypoxia-induced retinal neovascularization.
      The inhibition was dose dependent with highly significant decrease of neovascular
      nuclei counts among eyes treated with 0, 1.6 mg/kg, 16 mg/kg and 48 mg/kg doses.
      There appears to be a saturation effect of inhibition at the level of 70% at the
      two highest doses of 16 mg/kg and 48 mg/kg. CONCLUSIONS: AG3340 administered
      systemically significantly inhibits oxygen-induced retinal neovascularization in
      an animal model and appears to be a promising candidate for the treatment of
      neovascular retinal diseases.

PMID- 12187493
TI  - Efficacy and safety of microspheres of cyclosporin A, a new systemic formulation,
      to prevent corneal graft rejection in rats.
AB  - PURPOSE: To evaluate the efficacy and safety of a new systemic formulation of
      cyclosporin A (CsA)-loaded microspheres in a rat model of penetrating
      keratoplasty rejection. METHODS: Female Lewis rats received orthotopic corneal
      allografts from inbred female Fisher donors. The rats were divided into three
      groups: 1, untreated controls; 2, daily subcutaneous injection of 10 mg/kg of the
      commercially intravenous CsA formulation starting after surgery (time 0) and for
      15 days; and 3, one subcutaneous injection of 150 mg/kg of CsA microspheres. The
      grafts were evaluated clinically for 30 days and the rejection index, mean
      survival time, and rejection rate were calculated. Serum levels of CsA were
      measured at 5, 10, 15, 20, and 30 days in groups 2 and 3. Eyes, liver, and
      kidneys were histologically evaluated at the end of the experiment. RESULTS:
      Graft rejection was significantly reduced in group 3 at day 30 (P < 0.05) and
      serum levels of CsA were constant (range, 73.28 +/- 43.93 to 183.33 +/- 83.69
      ng/ml). High levels (>3000 ng/ml) were obtained in group 2 as long as CsA was
      injected. Both formulations delayed rejection onset, but only the microspheres
      decreased the rate of corneal graft rejection (100% in group 2 and 70% in group 3
      at day 30). Histologic examination showed no hepatic lesions with either
      formulation, but both resulted in deposition of a hemoglobin-like material in the
      kidneys. CONCLUSIONS: Although subcutaneous CsA-loaded microspheres delay
      rejection onset and decrease the rate of corneal graft rejection in an orthotopic
      keratoplasty rejection model in rats, administration of the microspheres did not
      prevent acute renal toxicity.

PMID- 12187494
TI  - New strategy for in vivo transgene expression in corneal epithelial progenitor
      cells.
AB  - PURPOSE: Efficient in vivo gene transfer into corneal epithelial cells and stable
      transgene expression would have broad clinical applications. We therefore
      assessed the capacity of adenoviral, adeno-associated viral (AAV) and lentiviral
      vectors encoding enhanced green fluorescent protein (EGFP) to transduce rat
      corneal epithelial progenitor cells. METHODS: Superficial cells of the corneal
      epithelium were shaved, after which 20 microl of the respective vector solutions
      were inoculated onto the basal cell layer of the limbal epithelium for 30 min.
      Results. Three days after transduction, fluorescence microscopic examination
      revealed the presence of EGFP+ cells in all corneas, irrespective of the vector
      used; however, EGFP+ cells were undetectable in corneas transduced with
      adenoviral and AAV vectors after 2 and 4 weeks, respectively. By contrast, EGFP+
      cells were still detected among cells transduced with lentiviral vector 6 weeks
      after transduction. DAPI (4', 6-diamidino-2-phenylindole) staining confirmed that
      it was the basal layer cells that continued to express EGFP throughout the 6-week
      period. CONCLUSIONS: The use of a lentiviral vector for in vivo transfer of
      foreign genes into corneal epithelial stem and transient amplifying cells may
      represent a new and effective approach to the treatment of corneal disease, as
      well as to the study of the biology of these stem cells.

PMID- 12187495
TI  - The effects of high ambient glucose on the radiosensitivity of retinal
      microvascular endothelial cells and pericytes.
AB  - PURPOSE: The metabolic peturbations of diabetes cause functional and structural
      changes in the retinal microvasculature which are termed diabetic retinopathy.
      Exposure of the eye to ionising radiation results in retinal vascular damage with
      a clinical manifestation known as radiation retinopathy. Anecdotal studies have
      suggested that exposure to even low levels of ionising radiation may accelerate
      development of pathological changes in the retinal vessels of patients with
      diabetes. This in vitro study was designed to test the hypothesis that the
      combination of a high ambient glucose environment (mimicking hyperglycaemia and
      diabetes) along with exposure to ionising radiation would result in more
      accentuated damage to cultured retinal vascular cells. METHODS: Retinal
      microvascular endothelial cells and pericytes were propagated for 5 days in
      either 5 mM (euglycaemia) or 15 mM (hyperglycaemia) glucose. Cells were
      irradiated with 250, 500 or 1000 cGy of ionising radiation using a 6 MV beam
      photon accelerator which was used for radiotherapy. Similarly treated but
      unirradiated cells were used as controls. DNA damage was assessed using the
      single-cell gel electrophoresis (comet) assay. RESULTS: Unirradiated control
      cells pre-exposed to glucose at either 5 mM or 15 mM for 5 days showed no
      significant difference in mean percentage tail DNA representing damage. However,
      in both pericytes and endothelial cells exposed to ionising radiation, cells
      cultured in 15 mM glucose showed significantly higher levels of DNA damage
      compared with those cultured in 5 mM glucose, with maximal differences being seen
      at the higher radiation doses (500 and 1000 cGy). CONCLUSIONS: This study has
      demonstrated that retinal microvascular cells cultured in high glucose express
      more DNA damage when exposed ionising radiation. These findings have important
      implications for the management of patients with diabetes if they require
      radiotherapy for neoplastic disease.

PMID- 12187496
TI  - Selective lesions of rabbit extraocular muscles injected with the anti-AChR
      immunotoxin saporin-mAb 73.
AB  - PURPOSE: To evaluate the effects on extraocular muscles of a skeletal muscle
      specific immunotoxin, saporin-mAb 73, as an alternative to botulinum toxin to
      induce a permanent correction of oculo-facial dystonias or some forms of ocular
      motility disorders. METHODS: An immunotoxin was prepared with a monoclonal
      antibody (mAb 73) against acetylcholine receptors of skeletal muscle, linked to
      saporin, a type 1 ribosome-inactivating protein (RIP) from Saponaria officinalis.
      Sixteen New Zealand white rabbits were treated with a single injection of
      immunotoxin directly into the medial rectus muscle of one eye. Four different
      dosages of 2, 5, 20, or 50 ng saporin-mAb 73 were used. The rabbits were
      sacrificed at two, 7 and 14 days post-injection. The medial rectus muscle and the
      retractor bulbi muscle of both the injected and the fellow eyes were taken and
      serial sections were examined by light microscopy in a blinded manner. RESULTS:
      Saporin-mAb 73, even at the dosage of 2 ng, brought about focal damage in the
      extraocular muscles of rabbits without histological changes in adjacent muscles.
      The histological examination revealed necrotic/apoptotic lesions restricted to
      the sites of inoculation and largely infiltrated by macrophages. No evident
      inflammatory reaction was detected at any time and neutrophils were substantially
      absent. At 14 days after injection, necrosis/apoptosis was still evident and the
      sclerotic reaction was minimal. CONCLUSIONS: The immunotoxin saporin-mAb 73
      injections into the extraocular muscles of rabbits caused focal damage to the
      muscles. There was no significant inflammatory reaction and muscle fiber loss was
      present even at the lower doses. Although the lesions were followed for only 14
      days, our results suggest that saporin-mAb 73 has potential to cause safe focal
      muscle damage but longer-term follow-up are needed to investigate the persistence
      of muscle weakness.

PMID- 12187497
TI  - Diffusion coefficients of retinoids.
AB  - PURPOSE: Diffusion coefficients of various retinoids have not been measured
      previously. It is important to know the diffusion coefficients of the retinoids
      because this property might be rate-limiting in dark adaptation. Also, retinoid
      diffusion is important to explore given that rhodopsin regeneration is not
      impaired in IRBP knockout mice. METHODS: Measurements of lateral diffusion
      coefficients (D) of 9-cis-retinal, all-trans-retinal, and all-trans-retinol were
      made by Fourier transform pulsed-gradient spin-echo NMR measurements (FT-PGSE
      NMR) in several solvents. Also,(3)H-all-trans-retinoic acid was used to measure
      diffusion from an aqueous agarose matrix and absorption into a toluene based
      scintillation fluid in a biphase assay. RESULTS: In a 1:1 mixture of
      CD(3)OD:D(2)O the D's of the retinoids were, 2.4 to 3.0 x 10(-6)cm( 2)/s. In the
      biphase assay,(3)H-all trans-retinoic acid exhibited a diffusion coefficient of
      2.3 x 10(-6)cm(2)/s. CONCLUSIONS: The lower than expected D for retinoids and our
      calculations suggest that mechanisms in addition to pure aqueous diffusion may be
      needed to account for normal rhodopsin regeneration rates in the mammalian
      retina.

PMID- 12187498
TI  - Circadian variations of transforming growth factor-beta2 and basic fibroblast
      growth factor in the rabbit aqueous humor.
AB  - PURPOSE: To compare levels of transforming growth factor-beta2 (TGF-beta2) and
      basic fibroblast growth factor (bFGF) in the ocular fluids of rabbits at various
      times of the day. METHODS: Seventy-two young adult New Zealand albino rabbits
      were entrained to a daily 12-hour light (6 AM to 6 PM) and 12-hour dark cycle.
      Eight rabbits were sacrificed at each of 6 time points: 4 AM, 8 AM, noon, 4 PM, 8
      PM, and midnight. Under an acute 24-hour constant dark condition, 8 additional
      rabbits were sacrificed at each of 3 time points in the accustomed light period
      (8 AM, noon, and 4 PM). Samples of aqueous humor and vitreous humor were
      collected from both eyes. Using enzyme immunoassay, samples from one eye were
      assayed for total TGF-beta2 and active form of TGF-beta2 and samples from the
      other eye were assayed for bFGF. Concentrations at various time points were
      analyzed using one-way ANOVA and post-hoc Bonferroni t-test for multiple
      comparisons. RESULTS: Aqueous humor levels of total TGF-beta2, active TGF-beta2,
      and bFGF changed during the 24-hour period. Total TGF-beta2 and bFGF levels
      increased between 4 AM and 8 AM. Active TGF-beta2 level increased between 8 PM
      and midnight. Similar patterns of changes were found when considering aqueous
      humor samples collected under the acute constant dark condition. In the vitreous
      humor, total TGF-beta2, active TGF-beta2, and bFGF remained unchanged throughout
      the 24 hours. CONCLUSIONS: Endogenous circadian rhythms of total TGF-beta2,
      active TGF-beta2, and bFGF occur in the rabbit aqueous humor. These two
      extracellular signaling molecules may be associated with specific physiological
      functions in the anterior segment according to the time of the day.

PMID- 12187499
TI  - The HYDILE trial: efficacy and tolerance of a quadruple combination of reverse
      transcriptase inhibitors versus the same regimen plus hydroxyurea or hydroxyurea
      and interleukin-2 in HIV-infected patients failing protease inhibitor-based
      combinations.
AB  - PURPOSE: To compare the efficacy and tolerance of a stavudine (d4T), didanosine
      (ddI), efavirenz (EFV), and abacavir (ABC) combination regimen with an identical
      regimen plus hydroxyurea (HU), or plus HU and interleukin-2 (IL-2), in patients
      failing protease inhibitor-based combinations and naive of EFV and ABC. METHOD:
      This was a randomized prospective trial in 69 HIV-infected patients recruited in
      one clinical center. Antiretroviral drugs were administered at standard doses
      according to weight. HU was added at week 6 at 500 mg twice daily. Three courses
      of IL-2 were given subcutaneously at 4.5 MU twice daily for 5 consecutive days,
      between weeks 24 and 40. The proportion of patients reaching plasma HIV-1 RNA
      <200 and <50 copies/mL was compared in the three trial groups at weeks 6, 24, and
      48 using intent-to-treat and as-treated analyses. CD4+ T-cell count changes from
      baseline were also assessed at the same time points, along with anthropometric
      and metabolic measurements. RESULTS: After 48 weeks, only 25% of patients
      receiving antiretrovirals had plasma HIV-1 RNA <200 copies/mL versus 59.1% in the
      group receiving HU and 56.5% in the group receiving HU and IL-2 (intent-to-treat;
      p <.01). At the 50 copies/mL cutoff, the results were 20.8%, 54.5%, and 47.8%,
      respectively. Most treatment discontinuations were due to failure in the first
      group and adverse events in the two others. A median decline of 27 CD4+ cells was
      observed in patients receiving antiretrovirals plus HU, against a gain of 78-118
      cells at week 48 in patients receiving antiretrovirals alone or in combination
      with HU and IL-2. More patients were affected by clinical fat atrophy symptoms at
      week 48 than at baseline. Additionally, a trend toward increased cholesterol
      levels was observed throughout the study. CONCLUSION: During this trial,
      virologic response in patients failing previous regimens was clearly enhanced by
      the addition of HU, despite d4T and ddI recycling. Although adverse events were
      more frequent in the HU-containing arms, no unexpected toxicity was observed and
      the blunted CD4 response prompted by HU was corrected by the addition of IL-2.
      The combination of HU with reverse transcriptase inhibitors can therefore be
      regarded as a valuable alternative for patients with few remaining therapeutic
      options.

PMID- 12187500
TI  - Randomized, placebo-controlled trial of product R, a peptide-nucleic acid
      immunomodulator, in the treatment of adults infected with HIV.
AB  - OBJECTIVE: The efficacy of Product R, a nontoxic peptide-nucleic acid, was tested
      in 43 HIV-infected adults naive to antiretroviral therapy. METHOD: Patients were
      randomized to receive Product R (21 patients) or placebo (22 patients). Dosage
      was two 1 mL subcutaneous injections daily on days 1-14, followed by 1 mL daily
      on days 22-28, 36-42, and 50-56. The follow-up period lasted until day 120.
      RESULTS: Mean root CD4 count increased in the Product R group during treatment
      and was significantly higher (p =.013) by the end of follow-up. Four Product R
      treated patients, but none of the control patients, experienced declines in viral
      load of >0.5 log. At the end of follow-up, the Product R group experienced a mean
      weight increase (p =.003), whereas the placebo group experienced a mean weight
      loss. The number of deaths and opportunistic infections were lower in the Product
      R group than in the placebo group (p =.076). No toxic effects were observed in
      any of the patients administered Product R. CONCLUSION: These findings suggest
      that Product R may have efficacy in the treatment of HIV-infected individuals.

PMID- 12187501
TI  - Safety and tolerance of efavirenz in different antiretroviral regimens: results
      from a national multicenter prospective study in 1,033 HIV-infected patients.
AB  - PURPOSE: To evaluate the incidence and severity of adverse events (AEs) and
      treatment interruption (TI) with efavirenz in a population with a high rate of
      intravenous drug use (IVDU). METHOD: This was a national, multicenter, and
      observational study of HIV-infected adult patients who were starting an efavirenz
      containing regimen. Evaluations of AEs were made in routine clinical practice at
      baseline and at least 3 months later. A total of 1,033 patients were included
      from 60 participating hospitals; 20% were antiretroviral naive. The risk factor
      for HIV infection was IVDU in 62.3%, and 6.6% of participants were on methadone.
      RESULTS: AEs affected 29.3% of participants, and treatment was interrupted in
      8.23%. The most frequent AEs were CNS disturbances that affected 24.1%
      participants; these AEs were considered related to efavirenz in 18.5% patients.
      AEs were not severe, and treatment had to be interrupted in 6% of patients. Other
      AEs were cutaneous rash (incidence of 5.9%; 2.4% of TI), gastrointestinal
      disturbances (1.45%; no TI), and elevation of liver function test (0.68%; no TI).
      Patients taking methadone had more AEs (39.7%), mainly CNS disturbances, and TI
      (19.1%). Cutaneous rash was more frequent among women. Psychoactive drug
      consumption, previous history of psychiatric disorders, antiretroviral
      experience, or previous nevirapine intolerance were not associated with higher
      incidence of AEs. CONCLUSION: Safety and tolerance of efavirenz is good in most
      patients, even in a population with a high rate of IVDU. The most common AEs are
      CNS disturbances; they are not severe and rarely lead to TI.

PMID- 12187502
TI  - TTV viral load as a marker for immune reconstitution after initiation of HAART in
      HIV-infected patients.
AB  - PURPOSE: To investigate whether TT virus (TTV) viral load may be used as a
      surrogate marker for functional immune reconstitution in HIV-infected patients
      receiving highly active antiretroviral therapy (HAART). METHOD: Fifteen protease
      inhibitor-naive HIV-infected patients were included in a longitudinal study. From
      each patient, three serum samples taken before HAART initiation and three samples
      taken during HAART were analyzed. TTV was detected by polymerase chain reaction
      (PCR) and was quantitated by competitive PCR. TTV viral heterogeneity was
      determined by restriction fragment length polymorphisms (RFLPs) and sequencing.
      RESULTS: All 15 HIV-infected patients were TTV positive. No significant change in
      HIV RNA or TTV viral load was observed at the three time points before HAART
      initiation. Even though HAART lead to an immediate and significant reduction in
      HIV RNA (p =.0001), a significant reduction in TTV viral load (p =.0002) was not
      observed until after 3-5 months of HAART. Four patients did not have an increase
      in CD4+ T cell count after 1 year of HAART; however, a decrease in TTV viral load
      was still observed, and three of these patients had a reduction in HIV RNA. RFLPs
      and sequencing revealed that TTV is represented as a heterogeneous population of
      virus in HIV-infected patients. CONCLUSION: This pilot study suggests that HAART
      leads to improved immunological responses, even in patients who do not have an
      increase in CD4+ T cell counts. We propose that the change in TTV viral load may
      be useful in the evaluation of cellular immune response at a functional level in
      HIV-infected patients who receive HAART.

PMID- 12187503
TI  - Comparison of nevirapine- and efavirenz-containing antiretroviral regimens in
      antiretroviral-naive patients: a cohort study.
AB  - OBJECTIVE: Efavirenz (EFV) was superior to nevirapine (NVP) in two recent cohort
      studies; but data from clinical trials suggest that three studies are needed to
      validate cohort results. We performed a cohort analysis comparing time to
      treatment failure and change in plasma HIV-1 RNA from baseline in antiretroviral
      therapy (ART)-naive individuals treated with NVP- or EFV-containing regimens.
      METHOD: A cohort analysis of three observational databases (N = >10,000 patients)
      found 1,078 ART-naive individuals treated with NVP-containing (n = 523) or EFV
      containing (n = 555) regimens. Patients were evenly matched and received at least
      three antiretroviral agents. The primary endpoint was time to treatment failure
      defined as a rebound in plasma HIV-1 RNA > 400 copies/mL. Other endpoints were
      change in plasma HIV-1 RNA from baseline and percent with plasma HIV-1 RNA <400
      copies/mL over time. Potential confounding variables were analyzed using the Cox
      proportional hazards model. RESULTS: Compared to EFV, NVP patients had a shorter
      time to treatment failure (307 days vs. 589 days; p <.001), less decrease in
      plasma HIV-1 RNA (-0.51 log vs. -1.32 log; p <.001), and fewer patients with
      plasma HIV-1 RNA < 400 copies/ mL (45% vs. 51%; p <.001). Significant factors for
      failure were baseline CD4 count (per 100 cell increase) or viral load (per log
      increase), treatment center, and year of entry (p <.05 for all comparisons).
      Race, gender, and background nucleoside use were insignificant factors.
      Multivariate analysis that included significant factors for failure demonstrated
      improved relative hazard with EFV compared to NVP (odds ratio = 0.50, p <.001).
      CONCLUSION: EFV-containing antiretroviral regimens were associated with superior
      clinical outcome, as measured by time to treatment failure. Results are
      commensurate with other large cohort studies comparing EFV and NVP.

PMID- 12187504
TI  - Salvage treatment with lopinavir/ritonavir (Kaletra) in HIV-infected patients
      failing all current antiretroviral drug families.
AB  - BACKGROUND: Lopinavir/ritonavir (Kaletra) is the latest available protease
      inhibitor (PI). It has shown greater potency than the former PIs in phase II/III
      trials, either in naive or in PI-experienced patients being naive for
      nonnucleoside reverse transcriptase inhibitors (NNRTIs). METHOD: We analyzed the
      first 138 patients recruited during the expanded access program in an HIV/AIDS
      reference center. Only patients who had significant past exposure to all three
      different antiretroviral drug families and who were failing their current
      regimens were chosen. RESULTS: A total of 93 and 76 patients completed,
      respectively, 3 and 6 months of follow-up. Mean plasma HIV RNA log(10) copies/mL
      before beginning Kaletra was 4.04 +/- 1.1 and mean CD4 count was 285 +/- 197
      cells/mL. Overall, 76.3% and 63.2% of patients showed a significant virologic
      response (defined as >1 log reduction in plasma HIV RNA and/or a reduction to
      less than 500 HIV RNA copies/mL) at 3 and 6 months, respectively. The mean CD4
      increase was +77.3 cells/mL at 6 months. Thirteen individuals did not complete 6
      months on therapy: there were 2 deaths (1 was non-AIDS related), 2 patients were
      lost to follow-up, 7 patients withdrew due to potential drug adverse events, and
      2 patients withdrew due to complications of intercurrent illnesses. Triglyceride
      levels significantly increased 3 months after initiation of Kaletra (+70 mg/dL; p
      =.04) while cholesterol levels remained stable (+7.7 mg/dL; p =.7). Sequence
      analysis at baseline showed a median number of PI mutations of 4 (0 to 12).
      Overall, 45% of patients harbored >/=5 PI mutations. Attainment of plasma HIV RNA
      <500 copies/mL occurred in 88% of patients with </=5 PI mutations but only in 48%
      of those harboring >5 PI mutations (p <.001). Baseline mutations at codons 71 and
      82 were associated with a lower response to Kaletra. CONCLUSION: Kaletra is
      relatively well tolerated and provides potent antiviral activity in heavily
      pretreated patients. Significant virological responses are seen in more than
      three quarters of patients at 3 months. Genotyping at the time of initiation of
      salvage therapy with Kaletra might help to predict which individuals will
      experience a greater benefit.

PMID- 12187505
TI  - Matrix metalloproteinase-9 and tissue inhibitors of matrix metalloproteinase-1 in
      plasma of patients co-infected with HCV and HIV.
AB  - BACKGROUND: Accelerated progression of hepatic fibrosis has been shown in
      patients co-infected with hepatitis C virus (HCV) and HIV. Liver fibrosis is a
      dynamic process in which the altered balance between matrix metalloproteinases
      (MMPs) and their specific inhibitors (TIMPs) may play a major role. METHOD: The
      involvement of MMP-9 and TIMP-1 in HCV liver disease progression in patients co
      infected with HIV was evaluated. Plasma concentrations of human MMP-9 and TIMP-1
      were assessed in 76 HIV-infected patients; 27 were co-infected with HCV and 49
      were HCV negative. 18 healthy donors were included as controls. RESULTS: Patients
      with HIV infection exhibited a striking increase in TIMP-1 levels; this is more
      evident in patients with advanced CD4 depletion. There was no elevation in the
      plasma concentrations of the MMP-9. The highest levels of TIMP-1 were found in
      the HIV/HCV co-infected patients. The values of TIMP-1 in HIV-infected patients
      with chronic HCV hepatitis were significantly higher than in HIV-positive
      individuals without HCV infection, even including those with low CD4 count. No
      significant differences were seen in the MMP-9 levels. CONCLUSION: These findings
      suggest that the altered balance between circulating MMP-9 and TIMP-1 during HIV
      infection may play an important role in exacerbating liver fibrosis progression
      in patients co-infected with HCV.

PMID- 12187506
TI  - Prevalence of HIV protease mutations on failure of nelfinavir-containing HAART: a
      retrospective analysis of four clinical studies and two observational cohorts.
AB  - BACKGROUND: Both D30N and L90M in HIV-1 protease are primary resistance mutations
      that emerge under nelfinavir drug pressure. Although D30N confers little or no
      cross-resistance to other protease inhibitors (PIs) and has been shown to allow
      effective substitution of a second PI, L90M with secondary mutations is involved
      in broad cross-resistance to the class. Although L90M has been observed rarely to
      date under nelfinavir selection, data on the relative incidence of these two
      mutations on failure of first-line nelfinavir HAART are sparse. METHOD: We
      performed a systematic review of HIV-1 protease genotypes from four clinical
      trials and two observational cohorts in which PI-naive patients failed to achieve
      or sustain full virological suppression on a nelfinavir-based first HAART regime.
      RESULTS: Wild-type protease was observed in 61.9% of 189 isolates and secondary
      PI mutations were observed in only <3%. D30N and L90M (+/- secondary mutations)
      occurred in 30.7% and 4.8%, respectively. Only one sample displayed both
      mutations (0.5%). CONCLUSION: Almost 95% of failures on first-line nelfinavir
      based triple-drug HAART occur without PI mutations or with D30N as the primary
      protease change. L90M occurs in only 5% of cases. These results are of
      significance for determining the feasibility of initiating a second PI after
      first-line nelfinavir failure.

PMID- 12187507
TI  - Clinical experiences with interferon as monotherapy or in combination with
      ribavirin in patients co-infected with HIV and HCV.
AB  - Human immunodeficiency virus (HIV) co-infection accelerates progression of
      hepatitis C virus (HCV) toward cirrhosis. Thus, with the increase of life
      expectancy observed after introduction of combination antiretroviral treatment,
      liver disease is becoming an increasing cause of morbidity and mortality in HIV
      infected patients. In addition, HCV co-infection blunts CD4 restoration induced
      by HAART and increases HAART hepatotoxicity. For all these reasons, anti-HCV
      treatment is mandatory in HIV seropositives. The perfect treatment of hepatitis C
      should not only be safe and effective, but it should not have any adverse impact
      on HIV diseases and concurrent anti-HIV therapy. Two drugs are currently licensed
      for treatment of HCV: interferon alfa (IFNalpha) and ribavirin. Three hundred and
      thirty-eight patients have been included in pilot studies on the efficacy and
      tolerability of IFNalpha monotherapy: 16% showed sustained response and 10%
      dropped out. No significant adverse impact of IFNalpha monotherapy on HIV
      diseases or antiretroviral treatment has been observed. IFNalpha and ribavirin in
      combination have been introduced more recently: only 88 patients were included in
      pilot studies published as full papers with a 25% sustained response and an 11%
      rate of drop outs. Anemia and cumulative toxicity with didanosine were the most
      important side effects of combination treatment, but it did not affect HIV
      disease progression. Higher rates of sustained response (33%) without increase of
      side effects have been observed in preliminary experiences with the new long
      acting pegylated interferons in combination with ribavirin. The search for the
      perfect treatment continues.

PMID- 12187508
TI  - Selected topics from the 9th Conference on Retroviruses and Opportunistic
      Infections.

PMID- 12187509
TI  - SPINK1 is a susceptibility gene for fibrocalculous pancreatic diabetes in
      subjects from the Indian subcontinent.
AB  - Fibrocalculous pancreatic diabetes (FCPD) is a secondary cause of diabetes due to
      chronic pancreatitis. Since the N34S variant of the SPINK1 trypsin inhibitor gene
      has been found to partially account for genetic susceptibility to chronic
      pancreatitis, we used a family-based and case-control approach in two separate
      ethnic groups from the Indian subcontinent, to determine whether N34S was
      associated with susceptibility to FCPD. Clear excess transmission of SPINK1 N34S
      to the probands with FCPD in 69 Bangladeshi families was observed (P<.0001; 20
      transmissions and 2 nontransmissions). In the total study group (Bangladeshi and
      southern Indian) the N34S variant was present in 33% of 180 subjects with FCPD,
      4.4% of 861 nondiabetic subjects (odds ratio 10.8; P<.0001 compared with FCPD),
      3.7% of 219 subjects with type 2 diabetes, and 10.6% of 354 subjects with early
      onset diabetes (aged <30 years) (P=.02 compared with the ethnically matched
      control group). These results suggest that the N34S variant of SPINK1 is a
      susceptibility gene for FCPD in the Indian subcontinent, although, by itself, it
      is not sufficient to cause disease.

PMID- 12187511
TI  - 75th anniversary of Andrija Stampar School of Public Health -- what can we learn
      from our past for the future?

PMID- 12187510
TI  - Genetic linkage of attention-deficit/hyperactivity disorder on chromosome 16p13,
      in a region implicated in autism.
AB  - Attention-deficit/hyperactivity disorder (ADHD) is the most commonly diagnosed
      behavioral disorder in childhood and likely represents an extreme of normal
      behavior. ADHD significantly impacts learning in school-age children and leads to
      impaired functioning throughout the life span. There is strong evidence for a
      genetic etiology of the disorder, although putative alleles, principally in
      dopamine-related pathways suggested by candidate-gene studies, have very small
      effect sizes. We use affected-sib-pair analysis in 203 families to localize the
      first major susceptibility locus for ADHD to a 12-cM region on chromosome 16p13
      (maximum LOD score 4.2; P=.000005), building upon an earlier genomewide scan of
      this disorder. The region overlaps that highlighted in three genome scans for
      autism, a disorder in which inattention and hyperactivity are common, and
      physically maps to a 7-Mb region on 16p13. These findings suggest that variations
      in a gene on 16p13 may contribute to common deficits found in both ADHD and
      autism.

PMID- 12187512
TI  - Childhood injury: call for action.
AB  - We aim to raise awareness of the burden of avoidable death and disability
      attributable to childhood injury in Europe in general and Croatia in particular.
      As formerly common causes of childhood death have declined, injuries have become
      the most important single cause of death in childhood in European countries. Yet,
      there are large differences between countries, and especially between the eastern
      and western parts of Europe. The existence of these differences, reflecting rapid
      declines in some countries, indicate the scope for prevention. But injuries are
      low on the policy agenda for various reasons, including their lack of visibility.
      We advocated the development of integrated intersectoral policies underpinned by
      an effective public health structure.

PMID- 12187513
TI  - Aiming for prevention: medical and public health approaches to small arms, gun
      violence, and injury.
AB  - The level of global small arms violence is enormous and the scale of human
      suffering it causes is immense, although poorly counted. It causes at least
      hundreds of thousands of deaths and more than a million injuries each year, as
      well as permanent physical and psychological damage, destruction of families,
      lost productivity, and diversion of resources from basic health services.
      Research is required on three basic issues, as follows: health effects of
      weapons; the contributing factors and causes, including behavioral issues; and
      impacts of interventions and their cost-effectiveness. Policies and programs
      designed to reduce the human and social impacts of small arms should make use of
      public health knowledge and analysis of risk factors as a means of bringing
      increased focus and effectiveness to their objectives. At its international
      conference on small arms, gun violence, and injury, "Aiming for Prevention" in
      Helsinki in September 2001, International Physicians for the Prevention of
      Nuclear War called on health professionals as well as scientists, activists,
      humanitarian and development workers to contribute to an effective confrontation
      of the small arms pandemic.

PMID- 12187514
TI  - Economic impact of injuries according to type of injury.
AB  - AIM: Analysis of the economic impact of injuries that occurred within a year in
      Motala district -- a World Health Organization Safe Community. METHOD: A survey
      of all types of injury that occurred in an area with the total population of over
      41,000 within a 12-month period (October 1, 1983, to September 30, 1984). All
      injuries that required medical care were noted. Included in the costs of injuries
      were the marginal costs to medical care, companies, and the health insurance
      system. RESULTS: There were 4,926 injuries that required medical care. The costs
      of injuries were SEK 23.7 million (US$3.59 million) for the health care service
      (outpatient care, including primary health care and hospital care), SEK 79.7
      million (US$12.08 million) for trade and industry, and SEK 9.1 million (US$1.38
      million) for health insurance system. Home injuries accounted for the largest
      share of community costs (29%). Men accounted for the highest share of both the
      cost to the community (59%) and health insurance expenditures (70%) for injuries.
      In case of home injuries, the cost of medical care dominated among women (46%),
      whereas company costs dominated among men (77%). Serious injuries (Abbreviated
      Injury Scale - AIS-3) accounted for 16% of the total cost to the community, but
      constituted only 3% of all injuries. Moderate injuries (AIS-2) accounted for 69%
      of the cost and made up 48% of the injuries, whereas minor injuries (AIS-1)
      accounted for 12% of the cost and constituted 49% of all injuries. Injuries to
      the extremities accounted in all for 74% of the cost to the community.
      CONCLUSION: The cost of injuries can be analyzed in relation to different
      characteristics of injuries, which can provide a comprehensive view of the injury
      profile and its economic impact according to the type of injury.

PMID- 12187515
TI  - Evaluation of community based intervention for the protection of children from
      small arms and explosive devices during the war: observational study.
AB  - AIM: To evaluate the influence of a community-based intervention aimed at
      reducing the risk of unintentional injuries caused by small arms and explosive
      devices accessible to children during the 1991-1995 war in Croatia. METHOD: From
      May 5 to June 15 in 1994 and 1995, we performed a cross-sectional survey on
      exposure of the children in Croatia to different small arms and explosive
      devices, using specially prepared questionnaires. The survey was conducted in
      Dubrovnik-Neretva and Karlovac counties, where community-based intervention was
      carried out, and Lika-Senj and Sisak-Moslavina counties, where only national
      intervention was implemented. The sample included a total of 5,317 parents and
      2,581 children. The response rate was 98%. All participants were asked to give
      answers according to current situation. RESULTS: Approximately a third of
      children in the counties without community-based intervention and a fifth in the
      counties with community-based intervention could access small arms and explosive
      devices at home. Boys were more exposed than girls (p=0.001). In the communities
      with community-based intervention, children were less exposed to the devices,
      such as small-arms, hand grenades, and explosives, which were the main cause of
      injuries. In 1994, parents in counties without community-based intervention
      handled weapons in front of their children in 45% cases vs 31% of those in the
      counties with community-based intervention (p<0.001). In 1995, the percentages
      were 44 and 32, respectively (p<0.001). CONCLUSION: Although it is impossible to
      quantify the exact amount of risk reduction due to health intervention alone,
      community-based intervention reduced the exposure of children to weapons.

PMID- 12187516
TI  - Impact of war on health related quality of life in Croatia: population study.
AB  - AIM: To present health-related quality of life in post-war Croatia, focusing on
      the population as a whole rather than on the specific group of people. METHOD:
      The study was conducted in six Croatian counties in the 1997-1999 period. Three
      of those counties had been directly affected by the 1991-1995 war. The sample
      consisted of 1,297 randomly selected respondents aged 18 years and older. The
      questionnaire was anonymous, consisting of questions on sociodemographic
      characteristics of respondents and Medical Outcome Study 36-item short-form
      health survey (SF-36). SF-36 comprised the following nine subscales: physical
      functioning (PF), role-physical (RP), bodily pain (BP), general health (GH),
      vitality (VT), social functioning (SF), role-emotional (RE), mental health (MH),
      and health transition (HT). RESULTS: Mean subscale scores for the areas directly
      affected by war were PF 64.21; RP 52.70; BP 59.35; GH 49.02; VT 49.52; SF 68.29;
      RE 63.02; MH 57.95; HT 41.28; and for the areas not affected by war were PF
      65.35; RP 62.01; BP 61.79; GH 50.45; VT 49.40; SF 71.41; RE 74.11; MH 60.33; HT
      45.14. The two areas differed significantly in RP (p<0.001), SF (p=0.035), RE
      (p<0.001), MH (p=0.038), and HT (p=0.003). Respondents living in the areas
      directly affected by war achieved lower total health-related quality of life
      scores. Younger respondents, respondents with secondary education, and those with
      lower income were the groups mostly affected by war. CONCLUSION: War affects self
      perceived health, physical ability, and emotional and mental health of the entire
      population affected by war, especially younger age groups, those with lower
      education, and lower income.

PMID- 12187517
TI  - Supplemental health insurance: did Croatia miss an opportunity?
AB  - Croatia continues to face a health-funding crisis. A recent supplemental health
      insurance law increases revenues through first increasing co-payments, then
      raising the payroll tax to cover those co-payments. This public finance "slight
      of-hand" will not solve the system's structural issues and may worsen system
      performance both in terms of efficiency and equity. Should Croatia have
      considered private supplemental insurance as an alternative? There is a new
      single private supplemental health insurance market now evolving over the EU
      countries and into Eastern Europe. Croatians could take advantage of lowered
      costs due to larger risk pooling and the lower administrative overhead of mature
      insurance organizations. Private supplemental insurance, when designed well, can
      address several objectives, including a) increased revenues into the health
      sector; b) removal of the public burden of coverage of selected services for
      certain population groups; and c) encourage new management and organizational
      innovations into the sector. Private and multiple company insurance markets are
      thought to be superior in terms of consumer responsiveness; choice of benefits;
      adoption of new, more expensive technology; and use of private sector providers.
      Private sector insurers may also encourage "spillover" effects encouraging
      reforms with public sector insurance performance. There is already an emerging
      private insurance market in Croatia, but can it be expanded and properly
      regulated? The private insurance companies might capture as much as 30-70% of the
      market for certain services, such as high cost procedures, preferred providers,
      and hotel amenities. But the Government will need to strengthen the regulatory
      framework for private insurance and assure that there is adequate regulatory
      capacity.

PMID- 12187518
TI  - Are medical savings accounts a viable option for funding health care?
AB  - AIM: To summarize the international experience of medical savings accounts
      (MSAs), make a preliminary evaluation of the impact of MSAs, and assess their
      feasibility in other countries, particularly Central and Eastern Europe. METHOD:
      A review of published literature in academic journals, books, Internet sources,
      and other "gray" literature. RESULTS: Most published studies were theoretical.
      Advocates argued that MSAs improved the efficiency of insurance, increased
      consumer choice, and reduced health care expenditures. Critics argued that MSAs
      led to adverse selection, reduced equity, resulted in cost inflation, and
      deterred necessary utilization. MSAs have been implemented in China, Singapore,
      the United States of America, and South Africa. The organization of MSAs varied
      between countries. MSAs were combined with either a public or private insurance
      element to cover catastrophic expenses. Few empirical studies of MSAs have been
      conducted and, therefore, the evidence on their impact is limited. CONCLUSION:
      More empirical evaluations are needed on the impact of MSAs. Results of empirical
      evaluations cannot be easily generalized but depend on the complementary systems
      of financing and the extent of state regulation. MSAs are not likely to be
      feasible in countries where the unemployment rate is high, savings rates and
      average earnings low, and the state weak.

PMID- 12187520
TI  - Low demand for substitutive voluntary health insurance in Germany.
AB  - AIM: To examine why the demand for substitutive voluntary health insurance in
      Germany is low. METHOD: A comparison of the benefits and costs of statutory and
      voluntary health insurance in Germany, based on a review of literature published
      in academic journals and books as well as gray literature. RESULTS: Employees in
      Germany with gross earnings over 40,500 Euros a year can choose to opt out of the
      statutory health insurance scheme (Gesetzliche Krankenversicherung, GKV) and
      purchase substitutive voluntary health insurance instead. Only a quarter of these
      employees and their dependents actually choose to opt out; the majority remain in
      the GKV. Substitutive voluntary health insurance does not generally afford
      greater benefits than the GKV in terms of services provided or choice of insurer
      and only affords marginal benefits in terms of choice of provider. It is also
      more expensive than the GKV for people with dependents, elderly people and people
      in poor health. Consequently, the choice to opt out and purchase substitutive
      voluntary health insurance is more likely to be taken by young, healthy or single
      people or couples with double incomes. CONCLUSION: Our analysis suggests that the
      demand for substitutive voluntary health insurance in Germany is low because the
      costs of opting out of the GKV are, in general, higher than the benefits afforded
      by purchasing substitutive voluntary health insurance. In the long term
      substitutive voluntary health insurance does not appear to provide good value for
      money when compared to the GKV, particularly for people with dependents, elderly
      people, and people in poor health.

PMID- 12187519
TI  - Citizens' views on health insurance in Croatia.
AB  - AIM: To examine the citizens' attitudes toward health insurance and its reform in
      Croatia, and their views on private payments for health care services. METHOD: In
      1999 and 2000, we surveyed 500 randomly selected adults from all regions of
      Croatia, aged 40 years and over. The questionnaire included questions on social
      health insurance, private payments for health care, and background information.
      The net response was 393 (79%). The analysis of the data collected included
      univariate and multivariate analyses to test the differences in the attitudes
      among sociodemographic and socioeconomic groups. RESULTS: Most interviewed
      Croatian citizens (83.2%) expressed the opinion that everybody should have access
      to health care services, irrespective of the health insurance contributions.
      However, 32.1% agreed that the utilization of services should depend on the
      payment of contribution; 39.1% believed that the money they contributed to health
      insurance corresponded to health care services they received; 60.1% agreed that
      insurance rate should increase proportionally to income. When asked about
      reforms, more than half (53.4%) thought that the current health insurance covered
      less benefits than 10 years earlier, whereas more than a third believed that
      changes offered more choice (36.9%) but less equity (37.7%), and 46% disagreed
      with the introduction of the basic package of health care benefits and
      supplementary insurance. About the same percentage of respondents thought that
      they had already been paying too much for health care out of their own pockets.
      CONCLUSION: Citizens in Croatia do not hold a positive opinion on health
      insurance reform. They fear the changes would bring about limitations in their
      social rights and increase their financial burden.

PMID- 12187521
TI  - Two ophthalmology departments financed by compulsory health insurance: what is it
      that makes a difference in costs and clinical effectiveness?
AB  - AIM: To identify factors contributing to significant differences between two
      university hospital departments of ophthalmology, one in Paris, France, and the
      other in Zagreb, Croatia, in their clinical effectiveness and cost-efficiency.
      METHOD: Structural, clinical, and financial characteristics of a Croatian and
      French ophthalmology department were compared for the 1996-2000 period. We used
      Paris ophthalmology department reports from 1996-2000 period as data source. Data
      on the Zagreb department performance for the same time period were obtained from
      the financial department. After comparative analysis of performance to show
      consistency and comparability of the two departments according to the type and
      prevalence of pathology, case-mix, and approaches to therapeutic, educational,
      and research activities, hospital budget analysis was performed, with special
      reference to the length of hospital stay according to diagnosis, number of
      examinations, material expenses, salaries, and investment. The variables analyzed
      were the number of emergency, regular, and hospitalized patients; number of
      physicians; number and type of surgical procedures; number of patients and length
      of hospital stay according to diagnosis; hospital budget distribution; and usage
      of hospital beds. RESULTS: Although the structure, technology, level of
      education, organization, and patient profile at the two departments were similar,
      the mean number of operative procedures per specialist per year was different
      (109.4 for Zagreb vs 199.2 for Paris). Hospital bed occupancy was 99.4% in Zagreb
      and 74.9% in Paris. The mean duration of hospital stay was 7.5 days in Zagreb and
      2.2 days in Paris. Zagreb had considerably longer hospital stay for all diagnoses
      except severe infections. Zagreb had lower investment in new technologies (0.4%)
      than Paris (20.1%), and higher material expenses (33.2% vs 10.1%, respectively).
      CONCLUSION: Different instruments of hospital services payment result in
      different clinical and organizational behavior of the hospital personnel and
      management. The three-fold longer stay in Zagreb can be explained by the
      mechanism of service payment, which is based on payment for capacity and
      structure and process in Zagreb instead of payment for service and service
      related outcomes in Paris. Comparison of the two departments indicates that
      clinical efficiency and effectiveness cannot and should not be separated from
      financial incentives that can stimulate (Paris) or discourage (Zagreb) rational
      and evidence-based clinical behavior.

PMID- 12187522
TI  - Years of potential life lost and valued years of potential life lost in assessing
      premature mortality in Slovenia.
AB  - AIM: To determine the leading causes of death that contribute most to premature
      mortality in Slovenia; to classify premature mortality according to the cause of
      death, age, and sex; and to determine the age point before which premature
      mortality becomes a potential loss to the society. METHOD: Potential economic
      losses to society were estimated by use of years of potential life lost (YPLL),
      with a cut-off point at 65 years, and valued years of potential life lost (VYPLL)
      methods. We calculated the sex-, age-, and underlying causes of death-specific
      YPLL and VYPLL for residents of Slovenia who died at age younger than 65 years,
      using Slovene sex-specific life expectancy for 1998/1999 and age-specific weights
      of investment-producer-consumer model. RESULTS: In 1998, 4,558 YPLL per 100,000
      population were lost to Slovenia. We found bimodal age distribution of YPLL, with
      the first peak in the 20-24 year age group and the second in the 45-49 year age
      group. Men to women rate ratio was 2.5. The leading causes of YPLL were external
      causes of death, followed by malignant neoplasms, and cardiovascular diseases.
      External causes, including suicides and traffic accidents, were the leading
      causes of death in men, whereas malignant neoplasms, including breast cancer and
      digestive cancer, were top-ranking causes in women. Among those, only external
      causes of death produced positive VYPLL, indicating a net loss to the society.
      CONCLUSION: In Slovenia, YPLL peaked in the 20-24 and 45-49 year age groups. Only
      external causes of death, most of which were preventable, accounted for the net
      economic loss to Slovenian society. We believe that YPLL and VYPLL, as specific
      mortality measures, can be reliably used in the evaluation of leading causes of
      death before age 65 and potential economic loss to the society caused by those
      deaths, and that they should be taken into account when setting public health
      priorities.

PMID- 12187523
TI  - Reforms of health care system in Romania.
AB  - AIM: To describe health care reforms and analyze the transition of the health
      care system in Romania in the 1989-2001 period. METHOD: We analyzed policy
      documents, political intentions and objectives of health care reform, described
      new legislation, and presented changes in financial resources of the health care
      system. RESULTS: The reforms of the health care system in Romania have been
      realized in a rather difficult context of scarcity of financial and human
      resources. The Gross Domestic Product spent on health care in 2000 was 4% and the
      number of physicians in 1999 was 42,975. The main changes due to the legislative
      reforms have been the introduction of a new social health insurance and
      strengthening of the position of family physicians. Negative effects of the
      reforms have been the decrease in health care accessibility and growing inequity
      in utilization of health care services. Health care users still pay physicians
      under-the-table, and have more out-of-pocket health care expenses. CONCLUSION:
      Future reforms in Romania should encourage the positive effects of current
      reforms: free choice of physician, autonomy of the primary health care system,
      and increasing financial resources for the health care system.

PMID- 12187524
TI  - Comparative approaches to pharmaceutical price regulation in the European Union.
AB  - AIM: To review pharmaceutical price regulation methods in countries of the
      European Union (EU), in terms of the anticipated impact of regulation on
      pharmaceutical expenditures and evidence of actual outcomes. METHOD: An extensive
      search was performed of medical and economic studies on regulatory interventions
      specifically targeting pharmaceutical prices in EU countries, published between
      January 1990 and April 2002. Both peer-reviewed and "gray" literature were
      systematically reviewed. RESULTS: Four principle approaches to pharmaceutical
      price regulation with some methodological differences were identified in EU
      countries, as follows: fixed pricing, cost-effectiveness pricing, profit
      controls, and reference pricing. Actual evidence of the impact of price
      regulation was limited in many of these countries. Cross-country comparisons
      suggested that limiting the rise of pharmaceutical prices did not equate to
      controlling the rise of pharmaceutical expenditures because of the volume effect
      of utilization. CONCLUSIONS: Supply-side regulation without the simultaneous use
      of demand-side incentives and volume controls does little to control the rise in
      pharmaceutical expenditures. The types of needed demand-side controls depend on
      the context of the individual country, on political priorities, and on the type
      of supply-side regulation in place.

PMID- 12187525
TI  - Encouraging the use of generic medicines: implications for transition economies.
AB  - Generic drugs have a key role to play in the efficient allocation of financial
      resources for pharmaceutical medicines. Policies implemented in the countries
      with a high rate of generic drug use, such as Canada, Denmark, Germany, the
      Netherlands, the United Kingdom, and the United States, are reviewed, with
      consideration of the market structures that facilitate strong competition.
      Savings in these countries are realized through increases in the volume of
      generic drugs used and the frequently significant differences in the price
      between generic medicines and branded originator medicines. Their policy tools
      include the mix of supply-side measures and demand-side measures that are
      relevant for generic promotion and higher generic use. On the supply-side, key
      policy measures include generic drug marketing regulation that facilitates market
      entry soon after patent expiration, reference pricing, the pricing of branded
      originator products, and the degree of price competition in pharmaceutical
      markets. On the demand-side, measures typically encompass influencing prescribing
      and dispensing patterns as well as introducing a co-payment structure for
      consumers/patients that takes into consideration the difference in cost between
      branded and generic medicines. Quality of generic medicines is a pre-condition
      for all other measures discussed to take effect. The paper concludes by offering
      a list of policy options for decision-makers in Central and Eastern European
      economies in transition.

PMID- 12187526
TI  - Health technology: challenge to public health.
AB  - Health technology includes drugs, procedures, techniques, and equipment used by
      health professionals to provide health care, and the organizational and
      supporting systems within which the care is delivered. Such new technology may
      comprehend new drugs, new medical devices and appliances, new medical activities
      and surgical procedures, health promotion and disease prevention activities, and
      organizational and supporting systems. To achieve maximal use of available
      resources and constant selection among alternatives offered, health technology
      assessment is indispensable as a scientific effort to determine the extent to
      which and under what conditions a specific technology is efficacious, effective,
      safe, and cost-effective. Since today the greatest benefit to patients must be
      achieved at the lowest cost, one of the ways to achieve this goal is to promote
      health technology assessment and thus build the healthcare infrastructure on more
      scientific and objective foundations.

PMID- 12187527
TI  - Acquired immunodeficiency syndrome in Brazil.
AB  - AIM: To describe the acquired immunodeficiency syndrome (AIDS) epidemic in Brazil
      and analyze the impact of federal government measures addressing the problem
      since its onset. METHOD: Retrospective review of AIDS epidemic data from its
      onset in 1980 up to the last published data in June 2001. RESULTS: AIDS was first
      reported in Brazil in 1980. By 1988, all 27 Brazilian states had diagnosed cases,
      and until June 2000 more than half of Brazilian municipalities had recorded at
      least one case of the disease. The AIDS incidence reached its peak between 1996
      and 1997 (14.7 per 100,000 population), and then declined between 1998 and 2000
      to 9 per 100,000 population. In the last two decades, the proportion of deaths
      has been also significantly reduced. These were not random events, but reflected
      the efficiency of the program implemented by the Brazilian Health Ministry's
      Coordination on Sexually Transmitted Diseases and AIDS. The program includes an
      epidemiological surveillance modeling system, which records cases from several
      regular epidemiological bulletins; national network of diagnosis and monitoring
      of HIV-infected individuals (ill or not); highly active antiretroviral therapy
      available free to all patients; mother-infant protection program; educational
      programs on condom use; the introduction of the female condom; development of
      AIDS studies in different areas to provide practical solutions; constant
      preoccupation about drug costs accounting for the patent breaking; and national
      production of many drugs currently in use. CONCLUSION: Well-planned and
      implemented national program against AIDS can significantly reduce the burden of
      this disease to the population.

PMID- 12187528
TI  - Urging health system research: identifying gaps and fortifying tuberculosis
      control in Pakistan.
AB  - AIM: To assess the significance of health system research in reducing the burden
      of tuberculosis and improving the performance of National Tuberculosis Control
      Program in Pakistan. METHOD: Qualitative and quantitative content analysis of
      research papers on tuberculosis and influence of the research knowledge on the
      efficiency of the National Tuberculosis Control Program. RESULTS: We analyzed 268
      research papers on tuberculosis in Pakistan published in the 1960-2002 period,
      from both national and international perspectives. The majority of the studies
      covered epidemiology of tuberculosis (n=76) in Pakistan, whereas the rest of the
      papers addressed issues like pediatric tuberculosis (n=53), tuberculosis among
      Pakistani immigrants (n=35), tuberculosis-HIV synergism (n=24), care seeking
      (n=19), adherence with tuberculosis treatment (n=14), tuberculosis among women
      (n=12), tuberculosis prevention (n=12), directly observed treatment short-course
      (DOTS) strategy modification (n=5), tuberculosis drug resistance (n=7),
      operational research (n=5), tuberculosis case management (n=4), and research on
      Mycobacterium (n=2). Qualitative analysis revealed that research and spending on
      tuberculosis policy and nationwide tuberculosis interventions are not sufficient.
      Available research knowledge has not yet been translated into the tuberculosis
      policy and interventions. Furthermore, the lack of insight of the health system
      on community dynamics and tuberculosis intervention has led to failure in
      achieving the desired targets in tuberculosis control. CONCLUSION: Health system
      in Pakistan needs to improve tuberculosis control interventions by conducting
      extensive research on the various potential weaknesses in the field. For an
      effective tuberculosis eradication program in a highly endemic country such as
      Pakistan, health system research should be an integral part of the National
      Tuberculosis Control Program.

PMID- 12187529
TI  - Waters in Croatia between practice and needs: public health challenge.
AB  - AIM: To describe waters monitoring in Croatia and legislation status for their
      evaluation, and to present health-relevant data and long-term analysis of the
      Drava river water, which is used in drinking water production. METHODS: Survey of
      databanks of various Croatian institutions related to waters, and physical and
      chemical analysis of 13 surface water pollutants, applying HRN ISO laboratory
      methods. RESULTS: Since 1992 until 2000, water systems had 10% of contaminated
      samples, whereas local community and private water sources had 30% of such
      samples. Since 1981, 84 waterborne epidemics have been registered, affecting
      7,581 people with predominantly gastrointestinal problems. The Drava river
      monitoring revealed that lead, cadmium, and mercury concentrations have
      constantly exceeded, whereas nickel and copper remained within allowed values for
      the Drava river to be classified into the second category of surface waters. Both
      nitrates and nitrites have been increasing with time, nitrates exceeding and
      nitrites remaining within guideline values. Total phosphorus and nitrogen
      concentrations also increased with time, still being below allowed maximum
      values. Chemical oxygen demand has been decreasing. Alkalinity has been
      satisfactory. Salt burden has been increasing. Both drinking water quality
      assessment and surface water monitoring in Croatia use less parameters then
      recommended by World Health Organization or signed conventions. CONCLUSION: The
      quality of Drava water has been improving, but still does not fully conform to
      the second category of surface water. More parameters should be used in its
      monitoring, as recommended by EU conventions and laws.

PMID- 12187530
TI  - Phthalates in underground waters of the Zagreb area.
AB  - AIM: To determine whether and in what concentrations the underground waters,
      stream waters, spring water, and tap water from the Zagreb area contain
      phthalates -- compounds used as plastic softeners, which have recently been
      ascribed carcinogenic, mutagenic, and teratogenic effects. METHOD: The presence
      of dimethyl phthalate (DMP), diethyl phthalate (DEP), dibutyl phthalate (DBP),
      benzylbutyl phthalate (BBP), diethylhexyl phthalate (DEHP), and dioctyl phthalate
      (DOP) was determined in a total of 96 samples of underground waters, stream
      waters, and tap water from the Zagreb area between February and June 1998.
      Identification and quantification of phthalates were performed by the method of
      gas chromatography (GC-ECD), with a detection limit of 0.005 microg/L. RESULTS:
      The presence of one or more phthalates was demonstrated in 93 out of 96 (97%)
      water samples. The measured values ranged from 0.005 to 18.157 microg/L.
      Phthalates were detected in 76 out of 77 (98%) underground water samples. The
      mean level of all phthalates present in the water samples was 4.879 microg/L.
      Median test yielded a significantly increased level of phthalates in the
      underground waters from Jakusevac (sampled in February 1998) and Trebe , which
      are Zagreb and Samobor city waste dumps, as compared with other sites in the
      study (overall median=3.785; chi-square=22.682; p<0.001). Phthalates were found
      at a mean concentration of 3.363 microg/L in all 10 water samples from the Sava
      river, the major source of the Zagreb alluvium underground waters. In case of
      drinking water, phthalates were detected in 7 out of 9 (78%) samples, at a mean
      concentration of 0.887 microg/L. As expected, DEHP was the most commonly detected
      phthalate, found in 78 (81%) water samples. CONCLUSION: The highest phthalate
      concentrations were recorded in underground waters directly related to the
      proximity of a waste dump. The levels of phthalates recorded in this study were
      lower than those reported from other countries and did not present a threat to
      human health. Environmental phthalate monitoring should be continued and their
      maximum allowed concentrations should be prescribed by regulations.

PMID- 12187531
TI  - Incidence of malignant pleural mesothelioma in coastal and continental Croatia:
      epidemiological study.
AB  - AIM: To evaluate the actual incidence of malignant pleural mesothelioma in
      Croatia, geographical distribution of the disease, and relevance of occupation
      and some other characteristics of diseased subjects. METHOD: Data on the
      incidence of pleural mesothelioma over a seven-year period (1991-1997) were
      collected from the Croatian Cancer Registry. In each case, the tumor diagnosis
      was histologically verified. Registration of the patients was based on their
      place of residence. Also, in 2001, a short questionnaire was sent to patients'
      families to gather additional information on patients' occupation (exposure to
      asbestos), smoking habits, and length of residence in the registered place. In
      many cases some of the answers had to be clarified by telephone or through a
      personal contact. Data obtained from 20 counties (administrative units) of
      Croatia were grouped into two larger areas: coastal and continental. The data for
      the city of Zagreb were presented separately. RESULTS: During the 1991-1997
      period, the Registry recorded a total of 248 malignant pleural mesotheliomas (197
      in men and 51 in women). The poll gathered additional data for 194 patients
      (78.2%): 153 (77.7%) men and 41 (80.4%) women. Eight in a million people on
      average were diagnosed with malignant pleural mesothelioma per year. Age
      standardized incidence rates (per 100,000) by residence showed an uneven
      geographical distribution for men: 2.66 in coastal area, 0.69 in continental
      area, and 0.75 in the city of Zagreb. Goodness-of-fit test for observed rates vs
      expected for Croatia were chi-square=145, df=2, p<0.001; post-hoc tests: coastal
      vs continental area chi-square=12.3, df=1, p=0.001; and coastal area vs city of
      Zagreb chi-square=4.4, df=1, p=0.035. In women with mesothelioma, these rates
      were 0.38, 0.24, and 0.18, respectively, and the differences were not
      statistically significant. CONCLUSION: Assuming that the information obtained by
      the poll on the occupation of diseased subjects was a true characterization of
      all recorded cases of pleural mesothelioma, more than two-thirds of subjects with
      the studied tumor had an occupational exposure to asbestos. Uneven distribution
      of the tumor, with higher rate in men in the coastal area, may be related to
      shipbuilding and other industrial sources of asbestos exposure in that part of
      the country.

PMID- 12187532
TI  - Public health training in Albania: long way toward a school of public health.
AB  - AIM: To assess the needs for a school of public health in Albania, where health
      system has been going through difficult periods of transition after the collapse
      of the communist regime and its "Soviet" health system in 1991. METHOD: Review of
      the past and current state of public health training, as well as the evolution of
      the main institutions involved in public health training in Albania, in view of
      the recent attempts undertaken to establish a school of public health. RESULTS:
      Up to early 1990s, public health training in Albania involved mostly physicians
      and was based to a great extent on sanitary engineering approach. In the mid
      1990s, the activities of the Department of Public Health of the Faculty of
      Medicine in Tirana focused on development of comprehensive public health training
      program. The aim of the current 2-year training program is to train public health
      specialists in a new fashion, in line with current international trends in the
      "new" public health. However, the size and the background of the faculty of the
      Department of Public Health (8 members, 7 physicians) is too limited and
      medically oriented. Since 1969, the Institute of Hygiene and Epidemiology (later
      National Institute of Public Health) has been providing short-term (1-3 months)
      courses for hygienists, chemists, and microbiologists working at the district
      level. CONCLUSION: Only the establishment of a school of public health capable to
      train specialists according to international standards can meet the health needs
      of Albania.

PMID- 12187533
TI  - Olive tree.

PMID- 12187534
TI  - Health technology assessment and quality of care.

PMID- 12187535
TI  - [Effects of free oxygen radicals on impaired lung oxygenating function at
      aortocoronary bypass surgery].
AB  - Fifty five patients with coronary heart disease were examined. Of them 10
      patients underwent multiple aortocoronary bypass surgery using intrathoracic or
      radial arteries under natural circulation, 45 had the same surgery under
      extracorporeal circulation (ECC). In the patients operated on without ECC,
      increases in active oxygen forms were rather moderate and practically always
      occurred with enhancement of antioxidative protective enzymes, the oxygen balance
      of arterial blood was in the normal range during and after surgery. The ECC
      patients displayed a considerable creatinine phosphokinase (CPK) with a lower
      antioxidative protection coefficient particularly when ECC was changed to natural
      circulation and when the lung was involved in circulation. In the postoperative
      period, the oxygenation index decreased from 1.7 to 1.3 in virtually all
      patients, the functional shunt rising from 15 to 30%. In 55% of the patients,
      varying arterial hypoxemia preserved in the early postoperative period. The
      damaging factors of ECC (hyperoxia, reperfusion syndrome, etc.) that impair the
      permeability of lung membranes have been shown to contribute to the activation of
      CPK, which causes early postoperative' arterial hypoxemia in patients operated on
      for coronary heart diseases.

PMID- 12187536
TI  - [Regulation of the functional status of the lower esophageal sphincter with
      gastrointestinal hormones in cardiospasm and reflux esophagitis].
AB  - A role of gastrointestinal hormones in the regulation of the lower esophageal
      sphincter was studied in 22 patients with cardiospasm and 21 with reflux
      esophagitis. The levels of gastrin, vasoactive intestinal polypeptide (VIP),
      glucagon, insulin, and c peptide were determined by radioactive assay before and
      after surgical treatment. In opposite abnormalities (cardiospasm and reflux
      esophagitis), there is a different degree of VIP secretion both at the beginning
      and after functional exercises. Before and after functional exercises, the level
      of VIP was higher than in those with cardiospasm. The value of VIP on fasting and
      after functional exercises may be an additional information to establish the
      diagnoses of cardiospasm and reflux esophagitis and to evaluate the efficiency of
      the treatment performed.

PMID- 12187537
TI  - [Sanitary and epidemiological welfare in the Russian Federation].

PMID- 12187538
TI  - [Morphological and biochemical features of cerebral beta-amyloidosis in long
      livers].
AB  - This is the first assessment of the pathogenetic values of some environmental
      factors in the occurrence and progression of cerebral beta-amyloidosis
      (Alzheimer's disease, senile dementia) in long-livers of different climatic areas
      of the Republic of North Ossetia-Alania. New isoenzyme serum assays for
      determining creatine kinase BB-isoenzyme and the transaminase activity in the
      spinal fluid are proposed, which may be used as potential markers in the
      biochemical diagnosis of Alzheimer's disease. They can both provide valuable
      information on the severity of morphological lesions of cerebral cells in
      Alzheimer's disease and serve as the basis for the differential diagnosis of
      different forms of dementia wherein dystrophic changes in CNS cells are absent or
      slightly pronounced.

PMID- 12187539
TI  - [Standard legal regulation and creation of a law code as the most important stage
      of public health reformation].
AB  - The significance of a law-making process is substantially increasing under the
      conditions of intensified expansion of the scope of standard legal regulation in
      the field of human health care in the Russian Federation. The authors state that
      any law-making process should begin with the definition of the subject-matter of
      a future law, its role and value in medical law creation and also indicate that
      the choice of the subject-matter of a future law is of priority and the most
      important stage of its preparation from the points of both contents-rich and
      standard legal views. Moreover, the paper presents main groups of issues that can
      determine the subjects of sociomedical laws and states the basic rules how
      reflect systemic relations in legislation. The paper shows it important to create
      a code of laws in the field of health protection for legal assurance of health
      public reforms.

PMID- 12187540
TI  - [Reforms and demographic crisis].
AB  - During reformation years all basic medical and demographic indices have undergone
      negative changes in Russia. Since 1992 there has been a steady-state decrease in
      the population due to the fact that mortality rates are extremely greater than
      birth ones. In 2001, the Russian population reduced in number by nearly a
      million. The birth rates are twice less than that requires for a simple
      reproduction of generations. Extremely high death rates remain among the
      population, in able-bodied males. The main reasons for the demographic crisis are
      the negative consequences of the implemented reforms rather than the transition
      from traditional to the new present-day reproduction of the population. It is
      problematic now to correct the situation via active migration of Russian-speaking
      persons. This requires enormous funds to provide comers with jobs and dwelling.
      It is unreal to diminish annual departure of 100 thousand persons, mainly young
      educated professionals from the country, though it is joust not only a
      demographic, but a strategic problem. In 2001 there was a some rise in birth
      rates. But this is the most illusive way of solving the demographic crisis. Just
      in the USSR, the high educational level of the population, the socioeconomic
      emancipation of females and progress in medicine gave rise to the transition to
      the present-day reproduction of the population, which is characterized by low
      birth and death rates. So the population is unlikely to be replenished by high
      birth rates. The main way of overcoming the demographic crisis is to reduce
      mortality and not to allow young people to die prematurely. For this it is
      necessary to know the biological mechanisms responsible for extremely high
      mortality. It is most likely to be due to breakdown in the dynamic stereotype of
      higher nervous performance, as stated by I. P. Pavlov. Today it is insufficient
      to control alcoholism, traumatism, and smoking by healthy lifestyle propaganda in
      order to reduce death rates in Russian. All these disasters took place after the
      Great Patriotic War, but an aspiration for long and happy life was prevalent in
      the consciousness of the people who has won the war. At present, neither the
      whole able-bodied population nor all young people have an internal aim at living
      long. To overcome this tragic gap in the consciousness requires primarily a great
      working motivation.

PMID- 12187541
TI  - [N. N. Burdenko is the founder and first President of the Academy of Medical
      Sciences].

PMID- 12187542
TI  - [Pain measurement and monitoring: basic and applied aspects].

PMID- 12187543
TI  - In memoriam: Julian M. Davidson.

PMID- 12187544
TI  - Once upon a time I met Alfred C. Kinsey.

PMID- 12187545
TI  - The effects of yohimbine plus L-arginine glutamate on sexual arousal in
      postmenopausal women with sexual arousal disorder.
AB  - This study examined the effects of the nitric oxide-precursor L-arginine combined
      with the alpha 2-blocker yohimbine on subjective and physiological sexual arousal
      in postmenopausal women with Female Sexual Arousal Disorder. Twenty-four women
      participated in three treatment sessions in which self-report and physiological
      (vaginal photoplethysmograph) sexual responses to erotic stimuli were measured
      following treatment with either L-arginine glutamate (6 g) plus yohimbine HCl (6
      mg), yohimbine alone (6 mg), or placebo, using a randomized, double-blind, three
      way cross-over design. Sexual responses were measured at approximately 30, 60,
      and 90 min postdrug administration. The combined oral administration of L
      arginine glutamate and yohimbine substantially increased vaginal pulse amplitude
      responses to the erotic film at 60 min postdrug administration compared with
      placebo. Subjective reports of sexual arousal were significantly increased with
      exposure to the erotic stimuli but did not differ significantly between treatment
      groups.

PMID- 12187546
TI  - Who are tomboys and why should we study them?
AB  - Tomboys are girls who behave like boys and, as such, challenge some theories of
      sex-typing. We recruited tomboys (N = 60) ages 4-9 through the media and compared
      them with their sisters (N = 15) and brothers (N = 20) on measures of playmate
      preference, sex-typed activities and interests, and gender identity. On nearly
      all measures, tomboys were substantially and significantly more masculine than
      their sisters, but they were generally less masculine than their brothers. We
      outline some scientific benefits of studying tomboys and describe some goals and
      initial findings of the Tomboy Project.

PMID- 12187547
TI  - Genetic and environmental influences on problematic masturbatory behavior in
      children: a study of same-sex twins.
AB  - Child sexual behavior problems, such as excessive or public masturbation, are
      often judged to result from environmental stress or trauma. We studied the
      relative importance of genetic and environmental factors for problematic
      masturbatory behavior among nonreferred prepubertal children. All twins born in
      Sweden in 1985-86 were identified from the Swedish Twin Registry. Parents, mainly
      mothers, completed Child Behavior Checklist (CBCL) ratings (Achenbach, 1991) for
      401 monozygotic (MZ) and 248 dizygotic (DZ) same-sex twin pairs (male-male or
      female-female) at age 7-9 years. Scores of two CBCL items concerning specific
      sexual behavior problems (Plays with own sex parts in public and Plays with own
      sex parts too much) were summed and the influence of genetic and environmental
      factors on variability assessed. The prevalence of problematic child masturbatory
      behavior was low and associated with other emotional and behavioral problems. The
      degree of problematic child masturbatory behavior resemblance was higher within
      MZ twin pairs as compared to DZ same-sex twin pairs. Model fitting indicated that
      genetic factors substantially influenced the studied behaviors (77%, 95% CI = 9
      96%), although family environment also played a role. Our results suggest that
      hereditary factors should be considered together with stressful experiences such
      as sexual victimization in the evaluation of elementary school children
      presenting with problematic masturbatory behaviors. When interpreting the
      findings, the very brief measure of sexual problem behavior and low statistical
      power, precluding the analysis of possible coinheritance with other symptoms or
      disorders, should be borne in mind.

PMID- 12187548
TI  - Test-retest reliability of the measurement of penile dimensions in a sample of
      gay men.
AB  - Both physiological and self-measurement methods have been employed to collect
      data on the dimensions of the erect penis. However, self-measurement using paper
      strips has often been favored as a less intrusive and time-consuming method,
      despite the recognition of the increased chance of bias through exaggeration. The
      current study aimed to establish the test-retest reliability of measurement of
      the erect penis using paper strips in a sample of 312 gay men. The men were
      issued with color-coded measuring strips printed with instructions but no
      calibrations, and asked to measure both the length and circumference of their
      partners' erect penis. Three months later they were asked to repeat these
      measures. Mean length on first measurement was 15.3 cm and 15.2 cm on second
      measurement. Mean girth at first measurement was 12.5 cm and 12.6 cm at second
      measurement. Test-retest reliability of measurement was found to be moderately
      low at r = .60 for length and r = .53 for girth. No relation was found between
      measurement discrepancy and the age, social class, education, ethnicity, or
      employment status of the partner taking the measurements. Although self
      measurement strips are both convenient and acceptable, and widely reported in the
      literature, they only have moderate test-retest reliability. This may be due to
      both natural variability in penis size within subjects over time and
      unreliability of the measurement method.

PMID- 12187549
TI  - Timing of pubertal maturation and heterosexual behavior among Hong Kong Chinese
      adolescents.
AB  - This study presents a cross-sectional examination of the independent contribution
      of pubertal maturation timing to heterosexual activity among Chinese adolescents.
      A standardized self-administered questionnaire was designed to obtain information
      on a spectrum of physical heterosexual behaviors from dating to sexual
      intercourse, age at first nocturnal ejaculation in boys, age at menarche in
      girls, and several psychosocial variables that might be associated with sexual
      behavior in adolescents. A total of 4,116 students aged from 14 to 18 years
      (2,175 boys and 1,941 girls) were recruited in the Youth Sexuality Survey of the
      Hong Kong Family Planning Association in 1996-97. When groups were defined as
      "early," "average," and "late maturers," among boys, early maturers were youngest
      to report dating and to have sexual intercourse, followed by average and late
      maturers. Among girls, late maturers were slower to date and have sexual
      intercourse, but early maturers showed no difference from average maturers. Age
      of maturation was significantly lower for those reporting all heterosexual
      behaviors for both sexes. Our findings illustrate culture's moderation of the
      expression of biological differences.

PMID- 12187550
TI  - A study of the STD/AIDS related attitudes and behaviors of men who have sex with
      men in Hong Kong.
AB  - A random population based study was carried out to understand HIV-related
      attitudes and behaviors and self-reported sexually transmitted diseases (STDs)
      among men who have had sex with men (MSM) in Hong Kong. A special computerized
      telephone survey method was used and 85 MSM were identified (from a total sample
      of 2,074 men), 47.1% of whom had at least one male sex partner in the past 6
      months. Among these 85 MSM, 29.4% had multiple partners and 37.5% had had anal
      sex in the last 6 months (67% of them were inconsistent condom users). MSM were
      more likely to have contracted at least one STD in the last 6 months (10.6%) and
      were less likely to perceive susceptibility for contracting HIV (62.4%) than
      those other respondents who visited a female sex worker (FSW) in the past 6
      months (4.3% and 43%, respectively). About 45% of the MSM did not perceive condom
      use to be efficacious for HIV prevention (vs. 30% for male clients of FSW). The
      study is limited by its small number; however, it suggests that MSM in Hong Kong
      may be at high risk of contracting HIV. Prevention programs should attempt to
      change attitudes (e.g., perceived efficacy of condom use, perceived
      susceptibility, awareness of risk involved, etc.) as well as behaviors. The
      feasibility for establishing a behavioral surveillance system for this population
      was demonstrated.

PMID- 12187551
TI  - [Expanding the grafts pool for pediatric liver transplantation with segmental
      grafts from living donor and cadaveric reduced size or split grafts].
AB  - AIM: To compare short and long-term results of pediatric liver transplantation
      (LT), utilizing segmental grafts from living donors (LD) vs. cadaveric (CAD)
      reduced size or split grafts. METHODS: A retrospective analysis of a single
      center experience (1993-2000), comparing the surgical outcome, the graft function
      and the survival rates between these groups. RESULTS: Of 195 LTs in pediatric
      recipients (age < 18), 48 (25%) were with LD grafts and 47 (24%) with CAD grafts
      (reduced size, n = 27, or split, n = 20). The mean age and weight of the LD
      recipients were 1.8 +/- 3 yrs and 9.0 +/- 8.1 kg vs. 3.5 +/- 4 yrs. and 15.2 +/-
      14.5 kg in the CAD group. The distribution of etiologies was comparable (EHBA,
      54% vs. 49%; inborn errors in metabolism, 12.5% vs. 12%; acute idiopathic hepatic
      failure, 12.5% vs. 14.2%). The severity of pretransplant disease and the fraction
      of acute hepatic failure cases were also comparable, although less LD grafts were
      used for urgent re-transplantation due to primary non-function or vascular
      complications (1 case in the LD group vs. 6 in the CAD group). The median warm
      ischemia time was similar (43 min; range, 28-87 min vs. 45 min; range 12-82 min),
      but the median cold ischemia time was significantly different (60 min; range 43
      298 in LD vs. 637 min; range, 342-1102 in CAD grafts). Both patient and graft
      survival in 3 months, 1 and 5 years were significantly superior in the LD group
      (patient survival, 97%, 91% and 89% vs. 82%, 70% and 62%, p < 0.001; graft
      survival, 92%, 89% and 77% vs. 66%, 59% and 52%, p < 0.005). The incidence of
      vascular complications (hepatic artery or portal vein thrombosis) and biliary
      complications (leak of stricture) was comparable (vascular, 10% vs. 7%, biliary,
      16% vs. 9%). The incidence of poor early graft function (6% vs. 21%) and primary
      non-function (2% vs. 18%) was significantly lower in the LD group. CONCLUSION:
      Although presenting similar surgical complexity, the outcome of segmental grafts
      from LD is better than of reduced size or split cadaveric grafts.

PMID- 12187552
TI  - [The hearing screening program for newborns with otoacoustic emission for early
      detection of hearing loss].
AB  - The importance of early detection of hearing loss is well known and screening
      programs for newborns are becoming more common throughout the world. The Hadassah
      hearing screening program for newborns using the Transient Evoked Otoacoustic
      Emission (TEOAE) test began in October 1999. All newborns are tested before
      discharge from the hospital. In case of inadequate results, the infant is
      scheduled for follow-up in 4 weeks in the Speech and Hearing Center, and
      according to results, a full audiological evaluation is performed. The high-risk
      population is also scheduled for follow-up. The preliminary results from 8,982
      newborns show that 93.5% passed the screening in the maternity ward, 4.2% failed
      unilaterally, and 2.2% failed bilaterally. The follow-up rate was low in the
      beginning, and improved due to proceeding letters and phone calls. The follow-up
      results show that we were able to detect 6 infants with a hearing loss under the
      age of 3 months, 4 of these infants belong to the high-risk group. We believe
      that TEOAE hearing screening for newborns is feasible and can help to detect hard
      of hearing children earlier than in the past. Undoubtedly, cost effectiveness
      considerations will be involved in implementation decisions.

PMID- 12187553
TI  - [Prevalence and etiology of anemia in an institutionalized geriatric population].
AB  - OBJECTIVE: Anemia is a common problem in the elderly, but its etiology in this
      age group is not well known, nor is its correlation with the mental and
      functional states. The objectives of the present study were to determine the
      prevalence of anemia in a large institutionalized geriatric population, to
      diagnose the etiology, and to analyze the correlation of anemia with the
      nutritional, mental and functional status. METHODS: The study was performed in a
      970 bed multilevel geriatric complex, from which 481 residents were randomly
      chosen. Their mean age was 81.4 +/- 8.7 years, and 46 of these residents were
      independent, 162 frail, and 273 nursing home patients. RESULTS: High prevalence
      of anemia (31.4%) was found, but, in more than half of the cases, the anemia was
      mild. The most common diagnosis was anemia of chronic disorders (65.6%), followed
      by anemia of chronic renal failure (13.2%). Anemia primarily due to iron, vitamin
      B12 or folate deficiency was found to be only 4%. In 15.9% of these cases the
      main cause of anemia could not be resolved. No correlation with the nutritional
      or cognitive states was found, but the functional state was highly and
      significantly inversely correlated with the presence of anemia. CONCLUSIONS:
      Anemia in institutionalized elderly is mostly the consequence of other chronic
      diseases. Further studies are required to determine whether a low functional
      state is an independent risk factor for anemia in old age.

PMID- 12187554
TI  - [Multifocal skin cancer with very severe destruction of the face in a patient
      refusing medical treatment].
AB  - We report a case of multifocal skin cancer of the face, in a 64 years old farmer
      who had refused medical treatment for about 12 years. Destruction of the entire
      face, including nose and eyes, was unusually extensive and severe, resulting in
      significant functional impairment and a fatal outcome. There are no legal means
      to enforce treatment upon a non-cooperative patient, regardless of the
      consequences, and there are no reliable ways available to the health insurer or
      the employers to enforce use of protective measures by individuals at risk.

PMID- 12187556
TI  - [Chronic cough].
AB  - The discomfort caused by persistent cough compels a great number of patients to
      seek medical aid. Persistent cough interferes with the patient's sleep,
      professional and social activities. The pathogenic triad of asthma, post nasal
      drip syndrome and gastroesophageal reflux disease, alone or in combination, is
      responsible for the majority of cases of chronic cough. Investigation of chronic
      cough, according to a rational protocol leads to the identification of the cause
      for chronic cough in approximately 90% of the cases.

PMID- 12187555
TI  - [Bilateral acute angle closure glaucoma following topiramate treatment].
AB  - We describe a case of bilateral acute angle closure glaucoma associated with oral
      topiramate therapy. A 64 year old woman developed bilateral acute angle closure
      glaucoma two weeks after beginning topiramate therapy for peripheral diabetic
      neuropathy. A topical and systemic anti-glaucomatous treatment were given and
      laser peripheral iridotomies were performed and, the intraocular pressure were
      stabilized. However, the anterior chambers remained very shallow and peripheral
      ciliochoroidal detachment was observed and confirmed echographically. Assuming
      that the mechanism of acute bilateral simultaneous angle closure glaucoma differs
      from the common pupillary block, and is related to external cause, the topiramate
      therapy was discontinued, and the patient was treated with cycloplegic agent and
      steroids. A gradual deepening of the anterior chamber and resolution of the
      choroidal edema were accompanied by improvement of visual acuity and corneal
      clarity. The presumed mechanism of drug related acute bilateral angle closure
      glaucoma is choroidal effusion and detachment associated with forward budging of
      the iris-lens diaphragm. This, in turn, causes a shallow anterior chamber and
      blockage of the ocular draining system.

PMID- 12187557
TI  - [Living-related segmental liver transplantation: broadening application in adult
      recipients].
AB  - Living-related liver transplantation using the left lateral segment has evolved
      as a surgical procedure in response to the need for size-matched grafts for small
      children. Experience gained with this procedure over the last decade and superb
      results led many centers to apply similar techniques for use of the right lobe
      for adults. Right lobe living-related liver transplantation is advantageous
      mainly for patients who otherwise would have long waiting periods for cadaveric
      organs, such as those with cholestatic liver disease or stable cirrhotic patients
      with small hepatocellular carcinoma. However, it is important to remember that
      living donors are healthy volunteers, and the risk associated with right
      hepatectomy is considerably higher than the risk of left lateral segmentectomy.
      The estimated risk for morbidity, mainly for bile duct leaks and intra-operative
      blood loss is about 5%, and the risk for mortality after right lobectomy is 0.2
      0.5%. Extended experience in liver resections and segmental liver transplantation
      techniques in children is a prerequisite before initiating an adult living
      related program. In addition, use of strict criteria for donor and recipient
      selection may lessen the risk associated with living donor liver transplants and
      thus further justify its use.

PMID- 12187558
TI  - [The role of complementary medicine in the treatment of incurable diseases].

PMID- 12187559
TI  - [Acupuncture for cancer patients: why not?].
AB  - Acupuncture is a complementary medical treatment whose use in cancer patients has
      been recommended by the American Cancer Society (ACS) for the treatment of cancer
      and treatment-related symptoms. Pain, nausea, breathlessness, vasomotor symptoms
      and limb edema have all been found to respond to this treatment modality.
      Accordingly to traditional Chinese medicine (TCM), acupuncture "disperses" the
      stagnation of energy which is thought to cause the tumor to form. As such, many
      acupuncturists are unwilling to treat cancer patients for fear of "dispersing"
      the tumor, as well as further compromising patients' immunity with this
      immunosuppressive treatment modality. Though it is true that care should be taken
      not to insert acupuncture needles in the vicinity of the tumor, there is no
      reason to fear "dispersal" of the tumor when using distant points, since this
      concept is one of TCM and not conventional medicine. In addition, the
      immunomodulatory effects of acupuncture, both via the release of pituitary beta
      endorphin and ACTH, as well as alleviating patient stress through relief of
      symptoms, are anti-carcinogenic. The medical establishment in Israel should
      consider recommending acupuncture for cancer patients.

PMID- 12187560
TI  - [The use of alternative medicine by multiple sclerosis patients].
AB  - This paper aims to present the results of a study that explores the use of
      uncontrolled and unexamined alternative treatment methods with 37 MS patients,
      and to compare these results with previous studies. The studied variables were:
      (a) reasons and circumstances of referral, (b) self reported outcome
      effectiveness of alternative treatment, and (c) satisfaction with the
      conventional physician and alternative healer. From a group of 37 patients, 17
      were referred to alternative healers. In comparison with those who were not
      referred to alternative medicine, the sub-group referred for alternative
      treatment reported more familial support and lower levels of satisfaction from
      their rapport with their conventional physicians.

PMID- 12187561
TI  - [The physician's role in assessing the fitness of elderly patients to drive].
AB  - With the aging of the population, physicians are increasingly faced with
      questions about patients' fitness to drive. When an older patient's driving
      competency is questioned, a comprehensive, step-by-step assessment is
      recommended. A discussion of the various considerations that are important in
      assessing and counselling drivers and their families regarding a patient's
      ability to drive safely is presented. The medico-legal aspects of the issue are
      also addressed.

PMID- 12187562
TI  - [Sexuality in aging].
AB  - During aging, impairment in many physiological functions is manifested. This is
      exhibited in sexual functioning, which is an intricate interaction involving a
      number of systems: endocrinal, motor, sensor, physical and sensual. Sexual
      activity is a component of the well-being of the individual, while sexuality is
      part of self-identity at any age. Sexual activity is a primary base to human
      relations, and it is a basic right of every person in society. Sexuality and
      sexual activity are considered to be part of youth, hence, the combination of
      sexuality and aging is considered strange. In many instances, sexual activity in
      the elderly is considered exceptional and possibly requiring certain intervention
      of the society establishment. Recent technological advances enable sexual
      activity, despite physiological and even anatomical shortcomings. Knowledge of
      the changes in sexual activity with aging, as well as having open communication
      on the subject, are the best tools for maintaining sexual activity with
      appropriate limitation during aging. The purpose of this short review is to
      present the different aspects of sexuality and sexual activity in aging.

PMID- 12187563
TI  - [Stress and hypertension].
AB  - Stress has many mental and biological effects. In this review we discuss the
      cardiovascular effects of mental stress and particularly, the relationship
      between stress and hypertension. The issues include: physiology, effect on blood
      pressure, job stress, white coat hypertension and the effect on the treatment of
      hypertension. This interaction could help us to understand the hypertension
      associated symptoms and to decide on the appropriate treatment.

PMID- 12187564
TI  - [Titin: some aspects of the largest protein in the body].
AB  - Titin, is definitely the largest protein in the body, with a molecular weight of
      3 million Dalton and composed of 27,000 amino acids. Paradoxically, this huge
      structure was elusive until the last decade but, since it was described in muscle
      tissue, its importance has rapidly emerged. Titin constitutes about 10% of muscle
      mass, to represent the third most abundant protein in the muscle following actin
      and myosin. It is estimated that titin acts like a "ruler" that controls the
      relative positioning of the latter 2 muscle proteins, and regulates the
      flexibility and "springiness" of the contracting muscle. Titin has also been
      implicated in the condensation of chromosomes during mitosis, while induced
      mutations in titin caused enhanced fragility of chromosomes. A recent
      demonstration of a high titer of autoantibodies to titin in sera of patients
      diagnosed with myasthenia gravis, is interpreted as a prognostic parameter to
      indicate a severe course of the disease.

PMID- 12187565
TI  - [Cerebral and physical risks associated with cannabis use].
AB  - This article summarize the results of research studies that indicate that the
      accepting, permissive approach to cannabis use is not justified. After
      theoretical introduction and a discussion of the forms currently available, we
      review research and epidemiological surveys demoting the effects of cannabis on
      various body systems. The deleterious effects associated with cannabis use and
      its derivatives are discussed.

PMID- 12187566
TI  - [Galeazzi lesion in children and adults: the undiagnosed lesion].
AB  - Unrecognized Galeazzi fracture dislocation of the wrist (distal radius fracture
      with radioulnar joint disruption) may lead to a high incidence of permanent
      functional disability and chronic pain. A high index of suspicion, early
      recognition, and acute treatment of distal radioulnar joint (DRUJ) instability
      will avoid chronic problems. This review examines the clinical presentation,
      diagnostic techniques, management and prognosis in children and in adults for
      this type of lesion.

PMID- 12187567
TI  - [Physical activity for the elderly].
AB  - Prolongation of life expectancy requires inevitable care for the quality of life
      of the elderly. Regular physical activity has a very important role in preserving
      the quality of life and independence, and not only reducing illness and
      mortality. A better understanding of this issue should enable us to set
      guidelines for regular physical activity for the elderly. The reaction to regular
      physical activity of older adults without cardiovascular diseases is similar to
      the reaction of young people to regular physical activity. In men, the mechanism
      of cardiovascular adaptation is mainly central, while in old women it is mainly
      peripheral. Elderly with cardiovascular diseases suffer from oxygen consumption
      and cardiac output reduction, compared to healthy old people. They also enjoy the
      cardiovascular benefits of aerobic physical activity and gain the risk factors
      profile improvement. Therefore, it is recommended to include aerobic physical
      activity as an integrative part of the daily lifestyle. Resistance strength
      training in elderly of both sexes leads to similar or even higher values for
      muscle mass and strength compared to young people, reduces the body fat mass,
      body weight and helps to preserve the active tissue mass. More beneficial effects
      of physical activity are: an improvement of posture and physical stability,
      improved flexibility and mobility capacity, a better cognitive function and a
      lower level of depression. The beneficial effects of physical activity in the
      very aged and frail elderly include physiological, metabolic, psychological and
      functional adaptations, which can substantially contribute to the quality of life
      and cannot be achieved by other treatments. SUMMARY: Participation in a regular
      physical activity program is an effective and secure means to avoid and reduce
      the functional decline associated with aging and to improve the quality of life.
      The recommended exercise program is multifactorial and includes aerobic and
      resistance training, and exercises of balance and flexibility.

PMID- 12187568
TI  - [Some evidence for the use of doctrine of signatures in the land of Israel and
      its environs during the Middle Ages].
AB  - The Doctrine of Signatures, was developed in Europe in the 16th and 17th
      centuries, though, its traces are spread until the present day in different
      traditional medicine cultures. This study traces the use of the Doctrine of
      Signatures in the medical and pharmacological literature of the Land of Israel
      and it's environs during the Middle Ages. The historical sources support the
      claim that although this theory did not originate in the region, it was certainly
      practiced there. These sources have revealed 23 substances with medicinal uses
      based on the Doctrine, bearing witness to the extent of its influence at the
      time: PLANTS: Common Agrimony, Common Balm, Common Snapdragon, Coral Peony, Corn
      Gromwell, Lebanon Barberry, Mullein, Orchid, Panther Strangler, Red Horned Poppy,
      Rhubarb, Rose of Jericho, Southern Maidenhair Fern, Spiny Broom, Sumach, Walnut,
      Wild Dog Rose. ANIMALS: Firefly, Red Coral, White Cuttle Fish. MINERALS: Red
      Chalk (Haematite), Sea Urchin, White Clay. The main categories of the Doctrine
      uncovered were: similarity between the substance used and the human organ;
      resemblance in shape or behaviour to a specific animal; correlation between the
      colour of a substance and the colour of the symptoms; similarities between the
      substance and the patient's symptoms and the use of a substance that might
      produce symptoms of a particular disease in a healthy person to remedy those same
      symptoms in one who is sick.

PMID- 12187569
TI  - Effectiveness and cost-effectiveness of echocardiography and carotid imaging in
      the management of stroke.

PMID- 12187571
TI  - Management of cancer symptoms: pain, depression, and fatigue.

PMID- 12187570
TI  - Management of chronic hepatitis C.

PMID- 12187572
TI  - Neonatal/pediatric intensive care ventilators.
AB  - Neonatal/pediatric intensive care ventilators provide temporary breathing support
      to preterm and critically ill children who require total or partial assistance to
      maintain adequate ventilation. Some ventilators are specifically designed for
      neonatal/pediatric patients, while others--which we call all-patient ventilators-
      can ventilate the full range of patients from neonates to adults. We evaluated
      six ventilators from four suppliers: Bird, Drager, Hamilton, and Siemens. Four of
      these units are all-patient models, a fifth can ventilate the range from neonatal
      to pediatric patients, and the sixth is suitable only for neonates. We found that
      the all-patient units performed at least as well as those designed specifically
      for neonatal/pediatric patients, and in fact all three of our Preferred units are
      all-patient ventilators. Unless your clinicians insist on the traditional time
      cycled pressure-limited (TCPL) mode, these all-patient units are probably your
      best choice--and may even save costs, as we discuss in the Money Matters feature.
      Safe and informed ventilator use is still a vital concern. We continue to stress
      the importance of thoroughly understanding the characteristics and use of every
      ventilator model in your facility. This means not only knowing the ventilator's
      modes, special features, and unique characteristics, but also knowing which alarm
      settings are appropriate and which are not. This article includes a review of the
      key points of that topic.

PMID- 12187573
TI  - Surgical robotics. Evaluation of the Computer Motion AESOP 3000 robotic endoscope
      holder.
AB  - The use of robots to manipulate surgical instruments inside the patient has
      already moved from the world of fiction to fact. While the widespread use of full
      function surgical robots is still many years away, less sophisticated robots that
      perform very specific surgical functions are already at a stage where the typical
      hospital can consider their use. Currently, the most affordable and commonly used
      type of "surgical-assist" robot is the robotic endoscope holder, which is used to
      hold and position rigid endoscopes during minimally invasive surgery. In this
      study, we introduce readers to the topic of surgical robotics, focusing
      specifically on robotic endoscope holders. The study includes a Technology
      Management Guide, in which we discuss who should and who shouldn't consider
      implementing such robots, and it includes our evaluation protocol and findings
      for one such robot, the Computer Motion AESOP 3000. We judged the evaluated
      system based on its performance relative to the human scope holders it is
      designed to replace, as well as its safety and ease of use. While we found the
      AESOP 3000 to be an acceptable, and sometimes preferred, alternative to the use
      of a human scope holder, we caution that many healthcare facilities won't see
      sufficient clinical benefit to warrant its purchase at this time.

PMID- 12187574
TI  - Playing with medical devices can be a deadly game.

PMID- 12187575
TI  - Unique configuration of Siemens Servo 300 and 300A ventilators could cause lung
      injury.

PMID- 12187576
TI  - [Paraneoplastic dermatoses].
AB  - Paraneoplastic dermatoses are important cutaneous markers of internal
      malignancies. They form a heterogenous group of skin diseases, where tumor
      induced immunologic factors, hormones, metabolic disorders and epidermal growth
      factor may play a role in the onset of the symptoms. The paraneoplastic skin
      disorder frequently refers to the type, localization and prognosis of the
      underlying tumor. The course of the tumor and that of the skin disease is
      generally parallel, which means that the cutaneous symptoms disappear when the
      tumor is treated and reappear in case of recurrence or metastasis. Seven rare
      obligate paraneoplastic dermatoses are known, where the skin marker is associated
      with neoplasia in almost 100% of the cases. The facultative paraneoplastic
      dermatoses are more common skin disorders, with a wider spectrum, and they are
      only associated with tumors in 3-30% of the cases. Authors present an overview of
      the clinical characteristics, etiopathogenesis and the underlying tumor of the
      most important paraneoplastic dermatoses.

PMID- 12187577
TI  - [Balloon catheter dilatation of lower gastrointestinal tract stenoses: long-term
      results].
AB  - AIM: Benign stenosis of the lower gastrointestinal tract usually develops, due to
      complication of a surgical intervention or sometimes because of other
      inflammatory bowel processes. Their reoperation is technically difficult and
      risky. Therefore the authors use a balloon catheter dilatation in the treatment
      of lower gastrointestinal tract stenosis since 1985. METHODS: First a guide wire
      is passed colonoscopically, then under X-ray control a double lumen balloon
      catheter, or directly through the channel of the endoscope a single or double
      lumen balloon catheter is introduced into the stenosis, which is then gradually
      dilated to 12-25 mm diameter. The applied pressure is 1.5-3 atm. Result of the
      dilatation can be judged from the decreased indentation of the balloon, and from
      increased diameter of stenosis at colonoscopic, or sometimes colonographic follow
      up. RESULTS: Between January of 1985 and July of 2001 they performed 123
      dilatation on 52 patients. The causes of stenoses were in 40 cases postoperative
      stenosis, in 5 Crohn disease, in 2 ulcerative colitis, in 1 ischemic stenosis,
      and in 3 scar of the anus. From all stenosis cases 4 were localised to the anus,
      40 to the rectum, 7 to the colon, and 1 to the terminal ileum. Due to the
      dilatation the average diameter of the stenosis was increased from 7.2 (1-14) mm
      to 19.7 (14-25) mm. Following the dilatation in 42 patients out of 52 the
      colonoscope was passed through the stenosis. Colostomies were closed in 11 cases
      out of 17. In 4 patients the subileus state ceased, and all of our 3 patients
      colo-cutan fistula healed rapidly. 16 out of 52 patients re-operation was
      proposed. One patient had fever as complication which was treated with
      antibiotics. CONCLUSIONS: Dilatation of benign stenosis of the lower
      gastrointestinal tract with balloon catheter is an effective method, which in
      most of the cases (69%) will stop the obstructive symptoms and in the long run
      therefore surgery can be avoided.

PMID- 12187578
TI  - [Role of osteopontin in the formation of microcalcifications in breast cancer].
AB  - INTRODUCTION: Osteopontin, a non-collagen, Ca-binding phosphoprotein, plays roles
      in both physiological and pathological mineralisation processes. Its expression
      may be severely altered in malignant tumours. AIM: To investigate the presence of
      this protein in breast tumours showing mammographic microcalcifications.
      MATERIAL: In this study the authors investigated immunohistochemically the
      osteopontin expression in 26 breast tumours. The elemental composition of the
      microcalcifications of the same tumours was also examined with energy dispersive
      spectrometer linked to a scanning electron microscope. RESULTS: Osteopontin
      expression was found within the tumours in the tumour cells, in vascular smooth
      muscle cells, in the myoepithelial cells of the normal ducts, and in macrophages.
      Extracellular osteopontin positivity was seen around calcified foci. There was no
      correlation between osteopontin positivity and the examined prognostic factors:
      grade, type and size of the tumour, axillary lymph nodes status, or age. Two
      types of microcalcifications were seen: 1. Ca-phosphate only, 2. Those composed
      of various other elements. CONCLUSION: The presence of osteopontin in the
      vicinity of calcified foci and in the vessel walls seems to support the
      hypothesis that osteopontin takes part in calcification process.

PMID- 12187579
TI  - [Detection of myocardial viability with venous contrast echocardiography
      immediately after reperfusion therapy in patients with acute myocardial
      infarction].
AB  - INTRODUCTION: After reperfusion therapy of acute myocardial infarction not only
      the patency of infarct related artery (IRA) but uncompromised myocardial
      perfusion are essential for recovery of myocardial contractile function. AIM: The
      authors sought to evaluate the relation between the status of myocardial
      microvasculature early after successful mechanical reperfusion therapy of AMI and
      contractile function at rest two weeks later. METHODS: Sixty-three patients with
      first acute myocardial infarction underwent venous myocardial contrast
      echocardiography (VMCE) 3 hours after successful percutaneous coronary
      intervention. The myocardial contrast intensity of akinetic segments was
      evaluated according to a semiquantitative score (1 = normal; 2 = moderate
      contrast defect; 3 = serious contrast defect; 4 = no contrast at all). Two weeks
      later the resting contractile function of previously akinetic segments (n = 218)
      was re-evaluated. RESULTS: The semiquantitative contrast score was significantly
      different between differential functional groups observed after two weeks:
      normokinesia (1.21 +/- 0.47); hypokinesia (1.65 +/- 0.77); akinesia (2.75 +/-
      0.85). Sensitivity and the specificity of semiquantitative venous myocardial
      contrast echocardiography for early prediction of functional recovery is 90% and
      69%, respectively (chi 2 = 76.2; p < 0.001). The global wall motion score index
      improved in contrast positive patients (more than 50% of initial akinetic
      segments show score 1 or 2) (1.607 +/- 0.30 vs. 1.295 +/- 0.25; p < 0.001), but
      did not change in the contrast negative patients (1.702 +/- 0.38 vs. 1.603 +/-
      0.33; p = NS). CONCLUSION: Functional recovery after AMI can be predicted with
      VMCE immediately after successful reopening of IRA. The post-PTCA contrast
      intensity of an infarcted segment is closely related to its subsequent functional
      status.

PMID- 12187580
TI  - [Emesis after pyloromyotomy in congenital hypertrophic pyloric stenosis:
      incomplete pyloromyotomy, recurring pyloric stenosis or gastric outlet
      obstruction?].
AB  - The authors present a case of an infant who was treated for recurrent vomiting
      following pyloromyotomy. Gastroscopic examination showed a polypoid tumour of 4-5
      mm in diameter located at the antral region. The patient recovered following re
      pyloromyotomy.

PMID- 12187581
TI  - [Indications for peri-operative temporary pacemakers].

PMID- 12187582
TI  - [Supplement to the paper Memory of Miksa Holbling].

PMID- 12187583
TI  - [Let's read the domestic literature. ACE-inhibitors and spironolactone-induced
      hyperkalemia].

PMID- 12187584
TI  - [Uterine metabolic activity].
AB  - The substrates of malate oxaloacetic cycle in the uterus and blood hormones
      (insulin, hydrocortisone, estradiol, progesterone, thyroid hormones) were studied
      in rabbit experiments. Stationary concentration of the malate oxaloacetic cycle
      substrata was determined and the role of hormones in the function of this cycle
      was detected, which helps evaluate the metabolic shifts regulating oxidation in
      uterine tissue.

PMID- 12187585
TI  - [Subpopulation blood lymphocyte composition in blood of patients with chronic
      hepatitis C during therapy with interferon].
AB  - The number of lymphocytes expressing CD3, CD4, CD8, CD16, CD25, and CD19 antigens
      was studied in patients with chronic hepatitis C before and after 12-week therapy
      with interferon-alpha (IFN-alpha). The percentage of cells expressing CD4+,
      CD16+, and CD25+ antigens decreased significantly in untreated patients, while
      the percentage of CD8+ and CD19+ lymphocytes was increased (p < 0.05) vs. the
      control. After 3-month therapy with IFN-alpha the counts of CD4+ and CD25+
      increased significantly in patients with chronic hepatitis C (p < 0.05 and p <
      0.01, respectively) in comparison with the initial values. The treatment led to a
      significant (p < 0.05) decrease in the number of CD8+ cells in the blood. The
      number of cells expressing CD19+ decreased, but remained high in comparison with
      the control. These results indicate that cellular immune response is inadequate
      in patients with chronic hepatitis C. Time course of subpopulation composition of
      T lymphocytes during effective treatment with IFN-alpha indicates an important
      role of T-cellular component of immunity in the antiviral defense mechanisms in
      chronic HCV infection.

PMID- 12187586
TI  - [Effect of hypoxia on immunologic parameters in patients with surgical
      infection].
AB  - Effect of tissue ischemia on immunity was studied in patients with developing
      surgical infection after injuries. Tissue hypoxia is one of the factors promoting
      the formation of immunity failure. Study of the course of immune reactions under
      conditions of hypoxia in suppurative infection of different etiology opens new
      diagnostic criteria and demonstrates the necessity of a differentiated approach
      to immunomodulating therapy of patients with local and total surgical infections
      of different etiology.

PMID- 12187587
TI  - [Optimization of gel radial diffusion method for serum immunoglobulin analysis].
AB  - Serum IgA, IgM, and IgG were measured by radial immunodiffusion in gel;
      immunoglobulin concentrations correlated with the diameter of their diffusion. A
      theoretically-based equation was derived; use of this equation will help estimate
      serum Ig content without plotting a calibration curve by the square diameter of
      the immunodiffusion ring of undiluted reference serum in a wide range of
      concentrations (0.3-3 mg/ml for IgA and IgM and 2-18 mg/ml for IgG). This
      modification of measuring serum immunoglobulins by radial immunodiffusion in gel
      is as accurate as other methods, but is reagent- and time-saving.

PMID- 12187588
TI  - [Federal system for external quality control of clinical laboratory procedures (a
      lecture)].

PMID- 12187590
TI  - [Optimization of results of laboratory measurements in patient biological
      specimens].

PMID- 12187589
TI  - [Changes in myocardial damage markers after radiofrequency ablation in patients
      with arrhythmias].
AB  - The aim of this study was to evaluate myocardial cell damage after radiofrequency
      ablation (RFA), one of the most effective methods for the treatment of
      arrhythmias. Thirty patients aged 30.4 +/- 8.6 years were examined. Biochemical
      parameters were evaluated repeatedly 6-18 h after RFA. Positive troponin T (Tn-T)
      test and increased CK-Mb activity (p < 0.22) were observed in 8 patients (group
      1), while in group II Tn-T test was negative. Biochemical findings in group I
      correlated with the results of ECG body surface mapping (STT) (negative area),
      duration and number of RFA lesions. Myocardial damage was detected using 3
      cardiac markers: myo/CK-Mb and Tn-T. These testing should be carried out in due
      time repeatedly, in order to catch the STT maps and biochemical parameters were
      in high correlation after RFA. Presumably, T-wave abnormalities in Tn-T-negative
      group after RFA were due to the cardiac memory phenomenon. Myo/CK-Mb after RFA in
      Tn-T-positive group coincided with that in acute myocardial infarction. Hence,
      myocardial damage after RFA can be confirmed by the Tn-T test, which is helpful
      in the differential diagnosis of minor myocardial damage and cardiac memory
      phenomenon.

PMID- 12187591
TI  - [Computer program for diagnosis, monitoring, and prophylaxis of cardiovascular
      diseases].
AB  - Cardiovascular diseases remain the main cause of death among adult population;
      their incidence can be reduced only using an effective system of primary and
      secondary prevention. The aim of our study was to develop software for automated
      recognition of cardiovascular risk factors, prognosis, and evaluation of
      dyslipoproteinemia phenotypes in lipid centers. Prognostic indexes, lipidogram
      values are estimated, and the program detects the risk factors (overweight, poor
      physical training, irrational nutrition, tobacco smoking, etc.) and predicts the
      summary risk of coronary disease. Neuronal network was used for evaluating the
      types of dyslipoproteinemias and for cardiovascular prognosis. The input vectors
      were lipid and lipoprotein concentrations. Output neurons were diagnostic signs
      of dislipoproteinemia phenotypes or cardiovascular prognosis.

PMID- 12187592
TI  - [Gas chromatography analysis of lipids in cell culture in viral infections and in
      serum of patients with various pathological conditions].
AB  - The results of gas chromatographic analysis of fatty acid composition of cell
      cultures infected with Coxsackie B viruses (CBV) and of sera of patients with
      unstable angina, psoriasis, and after stroke indicate that the presence of CBV in
      the organism can be one of the causes of lipid dysmetabolism.

PMID- 12187593
TI  - [Diagnostic and prognostic significance of study of acute phase proteins in
      children with appendicular peritonitis].
AB  - Acute phase proteins (fibrinogen, alpha 2-macroglobulin, alpha 1-antitrypsin)
      were measured in 47 patients with destructive appendicitis and 203 children with
      local (n = 121) and disseminated (n = 82) appendicular peritonitis. The patients'
      ages varied from 3 to 15 years. Control group consisted of 45 age-matched
      children with uncomplicated umbilical and inguinal hernias. The significance of
      acute phase proteins in the diagnosis and preoperative and postoperative
      treatment planning was evaluated.

PMID- 12187594
TI  - [Salivary thyroid hormones in evaluation of the functional state of the
      hypophyseal-thyroid system].
AB  - Thyrotropic hormone (TTH), total thyroxin (TT4), total triiodothyronine (TT3),
      free thyroxin (FT4), and free triiodothyroxine (FT3) were measured in the serum
      and oral liquid of clinically healthy subjects and patients with hypo- and
      hyperthyrosis. A relationship between hormone concentrations in the serum and
      oral liquid and the function of the pituitary-thyroid system was revealed. FT4,
      FT3, and TTH concentrations in the serum and oral fluid were in high correlation.
      This is regarded as an evidence of possible recretory origin of these hormones in
      the saliva.

PMID- 12187595
TI  - Deep vein thrombosis and air travel.

PMID- 12187596
TI  - Getting ahead of the curve: a new strategy for infectious diseases.

PMID- 12187597
TI  - Carpal tunnel syndrome.
AB  - Carpal tunnel syndrome is the most commonly diagnosed entrapment neuropathy. This
      review looks at the current body of evidence to help determine optimal practice
      for the diagnosis and management of this condition.

PMID- 12187598
TI  - Osteoporosis: prevention and diagnostic work-up.
AB  - Prevention of osteoporosis has assumed a paramount role in the decrease of
      osteoporotic fractures and the associated medical costs. A thorough diagnostic
      work-up of the patient with osteoporosis helps the physician exclude secondary
      causes of bone loss and acquire useful data for staging the disease, and
      contributes to planning the correct therapeutic management.

PMID- 12187599
TI  - Management of acute and chronic osteomyelitis.
AB  - The incidence of acute and subacute osteomyelitis is declining. Vaccination has
      almost eradicated Haemophilus bone infection in infants. However, chronic
      traumatic osteomyelitis is becoming more frequent following an increase in
      motorcycle accidents and infected internal fixation of fractures. There are now
      effective means of treating this using the Ilizarov external circular frame.

PMID- 12187600
TI  - Education in stroke: strategies to improve stroke patient care.
AB  - 'Stroke units save lives', but organized care requires expert staff and regular
      training to be effective. However, the quality of inpatient care for stroke
      remains poor, and stroke education is often fragmented between the health-care
      professions. This review describes some national and local strategies aimed at
      ensuring that all patients are cared for by expert staff.

PMID- 12187601
TI  - Acute lower limb ischaemia.
AB  - Salvage of the acutely ischaemic lower limb represents a large proportion of the
      emergency workload for the vascular surgeon. A successful outcome is dependent
      upon a careful clinical assessment and a prompt multidisciplinary approach to
      revascularization.

PMID- 12187602
TI  - Treating alcohol dependence in a district general hospital.
AB  - A strategy for managing alcohol problems within the general hospital setting
      should involve improved recognition of acute physical complications of alcohol
      withdrawal and dependence. Research shows that opportunistic interventions at
      this stage can reduce alcohol consumption by 25% in excessive drinkers. Support
      should be available from a local community alcohol service.

PMID- 12187603
TI  - TOBI: reducing the impact of pseudomonal infection.
AB  - Pseudomonas aeruginosa infection is associated with impaired lung function and
      reduced life expectancy in cystic fibrosis patients. Tobramycin nebulizer
      solution (TOBI, Chiron Corporation Ltd, Hounslow) has been specifically
      formulated for use against P. aeruginosa infection in the lung.

PMID- 12187604
TI  - Children's fractures 'not to be missed'.

PMID- 12187605
TI  - The Royal College of Physicians specialist registrar shift survey.
AB  - A survey of all medical specialist registrars in the UK reveals that a large
      majority oppose shift working patterns because of their adverse impact on
      training and quality of life, and on continuity and quality of patient care. This
      conflicts with the current drive to switch virtually all trainees to shifts by
      2004, to comply with the European Union Working Time Directive. More debate is
      urgently needed.

PMID- 12187606
TI  - Bouveret's syndrome: an unusual case of pyloroduodenal obstruction.

PMID- 12187607
TI  - Gall-stone ileus: imaging features.

PMID- 12187608
TI  - Pneumatosis coli in a case of caecal volvulus.

PMID- 12187609
TI  - Uterine haemorrhage controlled by an intrauterine balloon insufflated with hot
      water.

PMID- 12187611
TI  - Advanced nurse practitioners.

PMID- 12187610
TI  - Mediastinal lipomatosis and exogenous steroids.

PMID- 12187612
TI  - Anaesthetic management of the elderly surgical patient with cognitive impairment.

PMID- 12187613
TI  - Effects of resistive training and chromium picolinate on body composition and
      skeletal muscle size in older women.
AB  - This study assessed the effect of resistive training (RT), with or without
      highdose chromium picolinate (Cr-pic) supplementation, on body composition and
      skeletal muscle size of older women. Seventeen sedentary women, age range 54-71
      years, BMI 28.8 +/- 2.4 kg/m2, were randomly assigned (double-blind) to groups
      (Cr-pic, n = 9; Placebo, n = 8) that consumed either 924 micrograms Cr/d as Cr
      pic or a low-Cr placebo (< 0.2 microgram Cr/d) during a 12-week RT program (2
      day/week, 3 sets.exercise-1.d-1, 80% of 1 repetition maximum). Urinary chromium
      excretion was 60-fold higher in the Cr-pic group, compared to the Placebo group
      (p < .001), during the intervention. Resistive training increased maximal
      strength of the muscle groups trained by 8 to 34% (p < .001), and these responses
      were not influenced by Cr-pic supplementation. Percent body fat and fat-free mass
      were unchanged with RT in these weight-stable women, independent of Cr-pic
      supplementation. Type I and type II muscle fiber areas of the m. vastus lateralis
      were not changed over time and were not influenced by Cr-pic supplementation.
      These data demonstrate that high-dose Cr-pic supplementation did not increase
      maximal strength above that of resistive training alone in older women. Further,
      these data show that, under these experimental conditions, whole body composition
      and skeletal muscle size were not significantly changed due to resistive training
      and were not influenced by supplemental chromium picolinate.

PMID- 12187614
TI  - The effect of pre-exercise glucose ingestion on performance during prolonged
      swimming.
AB  - The purpose of this study was to determine if pre-exercise glucose ingestion
      would improve distance swimming performance. Additionally, pre-exercise glucose
      was provided at 2 different feeding intervals to investigate the affects of the
      timing of administration. Ten male triathletes (mean +/- SD: age, 29.5 +/- 5.0
      years; VO2peak, 48.8 +/- 3.2 ml.kg-1.min-1) swam 4000 m on 3 occasions following
      the consumption of either a 10% glucose solution 5 min prior to exercise (G5), a
      10% glucose solution 35 min prior to exercise (G35), or a similar volume of
      placebo (PL). Despite a significant difference (p < .01) in blood glucose
      concentration prior to exercise (mean +/- SD in mmol.L-1: G35 8.4 +/- 1.1 vs. G5
      5.2 +/- 0.5 or PL 5.3 +/- 0.4), no significant differences were observed in total
      time (mean +/- SD in minutes: G35 70.7 +/- 7.6, G5 70.1 +/- 7.6, PL 71.9 +/-
      8.4), post-exercise blood glucose (mean +/- SD in mmol.L-1: G35 5.1 +/- 1.1, G5
      5.1 +/- 0.9, PL 5.3 +/- 0.4), and average heart rate (mean +/- SD in bpm: G35
      155.8 +/- 10.8, G5 153.6 +/- 12.6, PL 152.0 +/- 12.5; p > .05). While not
      reaching statistical significance, glucose feedings did result in improved
      individual performance times, ranging from 24 s to 5 min in 8 of the 10 subjects
      compared to the placebo. These results were found despite significant differences
      in blood glucose between trials immediately prior to exercise.

PMID- 12187615
TI  - Influence of carbohydrate supplementation on plasma cytokine and neutrophil
      degranulation responses to high intensity intermittent exercise.
AB  - Ingesting carbohydrate (CHO) beverages during prolonged, continuous heavy
      exercise results in smaller changes in the plasma concentrations of several
      cytokines and attenuates a decline in neutrophil function. In contrast, ingesting
      CHO during prolonged intermittent exercise appears to have negligible influence
      on these responses, probably due to the overall moderate intensity of these
      intermittent exercise protocols. Therefore, we examine the effect of CHO
      ingestion on plasma interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-alpha)
      and lipopolysaccharide (LPS)-stimulated neutrophil degranulation responses to
      high-intensity intermittent running. Six trained male soccer players performed 2
      exercise trials, 7 days apart, in a randomized, counterbalanced design. On each
      occasion, they completed six 15-min periods of intermittent running consisting of
      maximal sprinting interspersed with less intense periods of running and walking.
      Subjects consumed either CHO or artificially sweetened placebo (PLA) beverages
      immediately before and at 15-min intervals during the exercise. At 30 min post
      exercise, CHO versus PLA was associated with a higher plasma glucose
      concentration (p < .01), a lower plasma cortisol and IL-6 concentration (p <
      .02), and fewer numbers of circulating neutrophils (p < .05). Following the
      exercise, LPS-stimulated elastase release per neutrophil fell 31% below baseline
      values on the PLA trial (p = .06) compared with 17% on the CHO trial (p = .30).
      Plasma TNF-alpha concentration increased following the exercise (main effect of
      time, p < .001) but was not affected by CHO. These data indicate that CHO
      ingestion attenuates changes in plasma IL-6 concentration, neutrophil
      trafficking, and LPS-stimulated neutrophil degranulation in response to
      intermittent exercise that involves bouts of very high intensity exercise.

PMID- 12187617
TI  - The influence of post-exercise macronutrient intake on energy balance and protein
      metabolism in active females participating in endurance training.
AB  - The purpose of this investigation was to determine the influence of post-exercise
      macronutrient intake on weight loss, protein metabolism, and endurance exercise
      performance during a period of increased training volume. Ten healthy young
      female endurance athletes performed 4 60-min bouts of cycle ergometry at
      approximately 65% of VO2peak on 4 days (day 1, 3, 4, and 6) during 2 separate 1
      week periods. On day 7, participants performed a ride to exhaustion at
      approximately 75% of VO2peak. One of the 7-day periods served as a control
      condition, where a placebo beverage was consumed following the exercise bouts on
      days 1, 3, 4, and 6 (CON). During the other 7-day protocol (POST), participants
      consumed a predefined formula beverage with added carbohydrate following the
      exercise bouts on days 1, 3, 4, and 6. Energy intake and macronutrient
      proportions were the same between the 2 trials; the only difference was the
      timing at which the macronutrients were consumed. Calculated fat oxidation was
      greater during exercise on day 6 during POST as compared to CON (p < .05).
      Glucose and insulin concentrations were significantly higher (p < .05) following
      exercise during POST as compared to CON. There was a trend (p = .06) for nitrogen
      balance to be greater on days 5 and 6 with POST as compared to CON. Time to
      exhaustion during exercise on day 7 was longer during POST as compared to CON (p
      < .05). POST resulted in a maintenance of body weight during the 7-day protocol,
      while there was a significant (p < .05) reduction with CON. It was concluded that
      post-exercise macronutrient intake following endurance exercise can attenuate
      reductions in body weight and improve nitrogen balance during 7 days of increased
      energy expenditure. Importantly, post-exercise supplementation improved time to
      exhaustion during a subsequent bout of endurance exercise.

PMID- 12187616
TI  - The effect of a high carbohydrate meal on endurance running capacity.
AB  - This study examined the effects of a pre-exercise meal and a carbohydrate
      electrolyte solution on endurance running capacity. Ten men performed 3 treadmill
      runs at 70% VO2max to exhaustion after consuming (a) a carbohydrate meal 3 h
      before exercise and a carbohydrate-electrolyte solution during exercise (M + C);
      or (b) the carbohydrate meal 3 h before exercise and water during exercise (M +
      W); or (c) a liquid placebo 3 h before exercise and water during exercise (P +
      W). Exercise time was longer in M + C (125.1 +/- 5.3 min; mean +/- SE) and M + W
      (111.9 +/- 5.6 min) compared with P + W (102.9 +/- 7.9 min; p < .01 and p < .05,
      respectively), and longer in M + C compared with M + W (p < .05). Serum insulin
      concentration at the start of exercise and carbohydrate oxidation rates during
      the first hour of exercise were higher, whereas plasma FFA concentrations
      throughout exercise were lower in M + W and M + C than in P + W (p < .01). A
      carbohydrate meal before exercise at 70% VO2max improved endurance running
      capacity; however, the combination of the meal and a carbohydrate-electrolyte
      solution during exercise further improved endurance running capacity.

PMID- 12187618
TI  - Caffeine, body fluid-electrolyte balance, and exercise performance.
AB  - Recreational enthusiasts and athletes often are advised to abstain from consuming
      caffeinated beverages (CB). The dual purposes of this review are to (a) critique
      controlled investigations regarding the effects of caffeine on dehydration and
      exercise performance, and (b) ascertain whether abstaining from CB is
      scientifically and physiologically justifiable. The literature indicates that
      caffeine consumption stimulates a mild diuresis similar to water, but there is no
      evidence of a fluid-electrolyte imbalance that is detrimental to exercise
      performance or health. Investigations comparing caffeine (100-680 mg) to water or
      placebo seldom found a statistical difference in urine volume. In the 10 studies
      reviewed, consumption of a CB resulted in 0-84% retention of the initial volume
      ingested, whereas consumption of water resulted in 0-81% retention. Further,
      tolerance to caffeine reduces the likelihood that a detrimental fluid-electrolyte
      imbalance will occur. The scientific literature suggests that athletes and
      recreational enthusiasts will not incur detrimental fluid-electrolyte imbalances
      if they consume CB in moderation and eat a typical U.S. diet. Sedentary members
      of the general public should be a less risk than athletes because their fluid
      losses via sweating are smaller.

PMID- 12187619
TI  - Nutrition knowledge and dietary composition in Italian adolescent female athletes
      and non-athletes.
AB  - This study aims to investigate dietary composition and nutrition knowledge of 60
      athlete and 59 non-athlete adolescent females (age, 14-18 years), using a 3-day
      food recall and a questionnaire on nutrition. The reported daily energy intake
      was similar in athletes and non-athletes, but less than the recommended and the
      estimated requirements. In the athletes, the energy supply from breakfast was
      higher than in the non-athletes (18.5 +/- 6.6 vs. 15.0 +/- 8.2%, p < .005).
      Energy intake from carbohydrates was higher (53.6 +/- 6.2 vs. 49.8 +/- 6.3%, p <
      .05) and that from lipids was lower (30.4 +/- 5.5 vs. 34.2 +/- 5.2%, p < .001) in
      athletes than in non-athletes. Athletes also showed higher fiber (20.0 +/- 5.8
      vs. 14.1 +/- 4.3 g/day, p < .001), iron (10.6 +/- 5.1 vs. 7.5 +/- 2.1 mg/day, p <
      .001) and vitamin A (804 +/- 500 vs. 612 +/- 456 micrograms/day, p < .05)
      reported intake than non-athletes. Calcium, iron, and zinc intake were less than
      100% RDA in both groups. Athletes gave a slightly higher rate of correct answers
      on the nutrition knowledge questionnaire (77.6 vs. 71.6%, p < .01) than non
      athletes. In conclusion, the overall recalled dietary intake and nutrition
      knowledge of the studied adolescent females show some misconceptions and nutrient
      deficiencies, but the results in athletes are quite better than in non-athletes,
      suggesting a favorable role of sport practice on dietary habits and nutrition
      knowledge.

PMID- 12187620
TI  - New Zealand jockeys' dietary habits and their potential impact on health.
AB  - The purpose of this study was to determine the nutritional status, eating
      behaviors, and body composition of 20 jockeys working in the New Zealand Racing
      Industry. Seven-day weighed food records showed the mean daily energy intake for
      male and female jockeys was 6769 +/- 1339 kJ and 6213 +/- 1797 kJ, respectively.
      Energy and carbohydrate intakes were below the recommendations for athletes, and
      the jockeys did not meet the RDI for a number of micronutrients. Of the jockeys,
      67% used a variety of methods to "make weight", including: diuretics, saunas, hot
      baths, exercise, and the restriction of food and fluids. A number of jockeys
      (20%) showed signs of disordered eating. Forty-four percent of jockeys were
      classified as osteopenic, and a number of factors may have contributed to this
      outcome, namely: reduced calcium intake, delayed menarche (14.5 years) in female
      jockeys, alcohol intake, and smoking. Percent body fat of male and female jockeys
      was 11.7 +/- 2.9 and 23.6 +/- 3.8, respectively. Current weight restrictions
      imposed on jockeys by the horseracing industry impacts on their nutritional
      status, which may compromise their sporting performance and both their short- and
      long-term health.

PMID- 12187621
TI  - An interview with Patti Steinmuller and Shawn Talbott about online courses in
      sports nutrition. Interview by Louise M. Burke and Mary P. Miles.

PMID- 12187622
TI  - [Evaluation of liver function with 13C-labelled amino acid using hepatectomized
      rat model].
AB  - Using a rat model of hepatectomy, we investigated whether the severity of
      hepatopathy could be quantitatively measured from changes in expiratory 13CO2
      levels after intravenous administration of L-[1-(13)C]phenylalanine, L-[1
      (13)C]methionine or L-[1-(13)C]alanine. MATERIALS AND METHODS: Under nembutal
      anesthesia, 30 mg/kg L-[1-(13)C]phenylalanine, 40 mg/kg L-[1-(13)C]methionine or
      20 mg/kg L-[1-(13)C]alanine was administered to rats through the femoral vein,
      and expiratory 13CO2 levels were measured for 15 min. Thirty percent, 70% or 90%
      hepatectomy was performed. In the control group, simple laparotomy was performed.
      RESULTS: The correlation coefficient between total 13CO2 output over 15 min after
      L-[1-(13)C]phenylalanine administration and liver weight/body weight was 0.883 (P
      < 0.001). The correlation coefficient between total 13CO2 output over 15 min
      after L-[1-(13)C]methionine administration and liver weight/body weight was 0.922
      (P < 0.001). The correlation coefficient between total 13CO2 output over 15 min
      after L-[1-(13)C]alanine administration and liver weight/body weight was 0.902 (P
      < 0.0001). CONCLUSION: In the breath test with intravenously administered L-[1
      (13)C]phenylalanine, L-[1-(13)C]methionine, or L-[1-(13)C]alanine, hepatopathy
      could be quantitatively evaluated by measuring expiratory 13CO2 levels over 15
      min.

PMID- 12187623
TI  - [Current state on development of neuroprotective agents for cerebral ischemia].
AB  - The improvement of decreased cerebral blood flow using thrombolytic agents, anti
      thrombin drugs, and antiplatelet drugs has been essential for acute ischemic
      stroke. Edaravone, a free radical scavenger, has been commercially available as a
      novel neuroprotective agent for ischemic stroke in Japan from 2001. The
      appearance of a neuroprotective agent implies that therapeutic strategy can be
      expanded through a combination with thrombolysis. In the previous development,
      several cases have reported that neuroprotective compounds failed in clinical
      trials. However, recent studies have clarified that the cerebral ischemia induced
      the neuronal cell death by mediating multiple mechanisms with necrosis and/or
      apoptosis. The cytotoxicity derived from the NO/peroxynitrite/free radical
      generating system, one of intracellular Ca2+ signaling, is a typical event in
      ischemic injury, which is protected by edaravone. Furthermore, it is suggested
      that suppression of excessively activated voltage-dependent Na+ and Ca2+ channels
      is effective as a strategy for neuroprotection, since abnormal excitatory stimuli
      in the neuronal network result in the cerebral infarction. The development of
      several compounds having different mechanisms of action for acute stroke is in
      progress. It is therefore prospected that the various novel neuroprotective
      agents will be provided for assuring the option of therapeutic strategy, since
      the reinforcement of medical stroke care including diagnosis contributes to the
      prolongation of the therapeutic time window.

PMID- 12187624
TI  - [Pharmacological and clinical properties of didanosine (VIDEX), a nucleoside
      reverse transcriptase inhibitor].
AB  - An active metabolite, ddATP, of didanosine that is an analogue of purine
      nucleoside (a component of nucleic acid) was known to inhibit the activity of DNA
      polymerase for E. coli. In 1985, Dr. Michiya et al. of NCI reported that
      didanosine and ddA inhibited replication of the human immunodeficiency virus
      (HIV). This discovery led to the clinical application of both the compounds.
      Didanosine, after being uptaken into a cell, becomes an active metabolite, ddATP,
      to inhibit a reverse transcriptase of HIV. Compared with zidovudine, didanosine
      has weak cytotoxicity both in vitro and in vivo. Didanosine, which is recommended
      as a first-line therapy drug in the Japanese Guideline on an anti-HIV Infection
      Therapy, was approved as twice-daily Videx Tablet and Dry Syrup formulations for
      launch in June 1992. In March 2001, a once-daily Videx EC Capsule formulation was
      approved and launched, having expected adherence improvements in HIV/AIDS
      patients.

PMID- 12187625
TI  - [GeneChip system from a bioinformatical point of view].
AB  - GeneChip (Affymetrix, Inc., USA) employs a specific method for spotting DNA
      probes on chips, which is different from any other DNA chips, and can complete
      the whole process from sample preparation to data construction and analysis. The
      GeneChip system can be applied to both gene expression analysis and genomic
      mutation analysis, which would play an important role in human genome analysis in
      the future. Techniques for data construction ("wet" experimental techniques),
      which are the major components in the GeneChip system, are generally established
      as routine work in the first screening process in most laboratories worldwide.
      The most important point would be how we exchange experimental data produced by
      researchers and gene/genome information available both on the public and the
      commercial bases so that we reduce useful information on gene expression.
      Recently, the center of the research has been shifting to computing technology
      for data processing ("bioinformatics"). This article separately deals with gene
      expression analysis and genomic analysis, with emphasis on bioinformatics. We
      describe the data on gene expression screening, the gene targeting process, the
      analysis of genomic DNA mutations using the P53 probe array, and the HuSNP
      mapping assays, by presenting our experimental examples.

PMID- 12187626
TI  - [Down-regulation of a gene-expression by an antisense BNA oligonucleotide].
AB  - We recently developed a novel nucleic acid analogue, Bridged Nucleic Acid (BNA),
      one of the most promising artificial nucleic acids for antisense and/or antigene
      methodology. The antisense effects of BNA modified oligonucleotides targeting the
      Internal Ribosomal Entry Site (IRES) in Hepatitis C Virus (HCV) RNA were
      evaluated. As a result, it was found that the antisense BNA oligonucleotides
      efficiently suppressed the targeted gene-expression in a sequence specific
      manner. Although the stem region in the mRNA is generally thought to be out of
      target for the antisense strategy, BNA oligonucleotide targeting the stem region
      in the HCV-IRES gave a positive antisense effect, also. It is quite noteworthy.

PMID- 12187627
TI  - [RNA interference for mammalian cells].
AB  - Knock-out of mammalian genes is technically troublesome and time-consuming
      compared to those of lower animals. RNA interference (RNAi) is a strategy of
      sequence-specific post-translational gene silencing, and it has been successfully
      applied for disruption of gene transcripts in C. elegans. Gene silencing by RNAi
      had not been accomplished in mammalian cells until recently, because bystander
      activation of DNA-dependent protein kinase (PKR) coincides to disturb gene
      silencing by long double-stranded RNA (dsRNA), resulting in non-specific
      repression of translation of many proteins. A breakthrough has come recently with
      a report suggesting that 20- or 21-bp duplex RNA with 2 bp 3' overhang are made
      by DICER protein that cleaves long dsRNA during RNAi reactions in vivo and the
      resultant short dsRNAs mediate RNAi. Those short dsRNAs, namely, small
      interference RNA (siRNA), barely activate PKR. Using synthesized 21 bp siRNA, T.
      Tuschl's group has challenged to establish an artificial RNAi method suitable for
      mammalian cells. Their report was favorable in that siRNA specifically suppressed
      targeted gene translation in mammalian cells during culture without activation of
      PKR. Recently K. Taira's group developed the vector-based siRNA expression system
      by which RNAi is feasible in mammalian cells. Almost all genes can be targeted by
      RNAi. RNAi methods require minimal time and labor; therefore, mammalian gene
      knockdown by RNAi will become popular in the near future.

PMID- 12187628
TI  - [The new technology for controlling gene function in zebrafish].
AB  - The technology for the control of gene function is necessary not only to study
      development, but also to study pharmacology and to invent new medicines.
      Morpholino oligo blocks mRNA translation and, as a result, inhibits gene
      function, mimicking the mutation of the gene. As the method is quite simple and
      effective, morpholino oligo has been an essential tool in developmental biology.
      Caged RNA is an innovative technology evolved in Japan. Caged RNA is reduced in
      translational activity, whereas illumination of caged RNA with ultraviolet light
      leads to recovery of translational activity. Using caged RNA, we will be able to
      activate the translation of any gene at any time and in any cell(s) we want.

PMID- 12187629
TI  - [Treatment of heart failure: an update].
AB  - During the last years, the results of several trials on heart failure treatment
      were published or presented at international meetings. The new perspectives
      concern drug therapy and non-pharmacological strategies, such as cardioverter
      defibrillators, biventricular resynchronization and implantable assist devices.
      Trials on beta-blockers extended the indication to patients with advanced heart
      failure, but the choice of the "best" beta-blocker to use remains an unsolved
      issue. Moreover, the concomitant use of ACE-inhibitors and angiotensin II
      receptor antagonists is a recent acquisition. However, the Val-HeFT results
      underscored that the add-on hypothesis of a more complete inhibition obtained
      with the combination of multiple agents was not confirmed in patients already
      taking ACE-inhibitors and beta-blockers. Regarding the new neurohormonal
      modulators (omapatrilat, etanercept, endothelin receptor blockers, arginine
      vasopressin antagonists), more data are needed before using them in clinical
      practice. After the publication of the MADIT-II results, the cardioverter
      defibrillator implantation will probably spread in patients with previous
      myocardial infarction and left ventricular dysfunction to prevent sudden death,
      but the cost-effectiveness ratio is still to be clarified. In the advanced or end
      stage heart failure, when the improvement of quality of life represents the main
      target of therapy, ventricular resynchronization and implantable assist devices
      may play a role in clinical settings. Before considering them like a real
      therapeutic option, final results from ongoing investigations should be awaited.

PMID- 12187630
TI  - [Mitral stenosis: echocardiographic evaluation].
AB  - The diagnostic tools available for the evaluation of mitral stenosis are two
      dimensional and Doppler echocardiography, which are able to identify morphologic
      and flow changes. Two-dimensional echocardiography can be used to assess the
      morphological appearance of the mitral valve apparatus, including its mobility
      and thickness and the presence of calcified leaflets and subvalvular fusion.
      Wilkins'score permits evaluation of each variable which, on the basis of its
      severity, is scored according to a point system ranging from 1 to 4. In patients
      with severe mitral stenosis, a low total score (< 8) and elastic symmetric
      commissures suggest valvuloplasty. A total score > 10 and the presence of more
      than mild mitral regurgitation or of calcification of both commissures suggest
      valvular replacement. The left atrial and ventricular chamber sizes and other
      associated valvular diseases can also be assessed at two-dimensional or Doppler
      echocardiography. The severity of obstruction can be assessed using two
      dimensional and Doppler echocardiographic area (pressure half-time, proximal
      isovelocity surface area, continuity equation) and with the mean transmitral
      gradient measured using a continuous wave Doppler signal across the mitral valve.
      Valvuloplasty can also be performed in patients with a high score when surgery is
      contraindicated. During follow-up it is necessary to evaluate the area, the mean
      gradient, the right ventricular systolic pressure and the presence of a residual
      atrial septal defect and mitral regurgitation. Restenosis is diagnosed when the
      valve area decreases to 50% of that achieved during valvuloplasty or surgery.

PMID- 12187631
TI  - [Echocardiography with reconstructed M-mode: technical aspects and clinical
      applications].
AB  - Reconstructed M-mode imaging is a new post-processing technique that permits the
      reconstruction of any cardiac structure and flow from cine-loops of different
      sources (tissue, color Doppler and tissue Doppler cine-loops) in M-mode format.
      This technique can be useful in a number of clinical situations and can
      facilitate the echocardiographic examination, allowing for correct and easy M
      mode analysis to be performed at any time, both at the patient's bedside as well
      as off-line. In this paper the fundamental technical features and current
      clinical applications of reconstructed M-mode imaging are illustrated and
      discussed.

PMID- 12187632
TI  - [Turin Network Project: global management of acute myocardial infarction first
      hours in the hospital territory. First results and the primary angioplasty
      registry, 2001].
AB  - In a previous paper we described a project of a telematic network in the area of
      Turin, aimed at decreasing acute myocardial infarction mortality, reducing the
      treatment delay, and facilitating the access to primary angioplasty. Here we
      present the Metropolitan Primary Angioplasty Registry, as a first result of the
      project, and the state of art of the network development, including facilities
      for electrocardiographic remote transmission.

PMID- 12187633
TI  - [Surgical correction with homograft in native or prosthetic aortic valve
      infective endocarditis].
AB  - BACKGROUND: Aortic valve surgery for infective endocarditis is still a high-risk
      procedure and the optimal valve substitute remains controversial. The aim of this
      study was to evaluate the results of our experience using homografts in the
      treatment of native (NVE) or prosthetic valve endocarditis (PVE). METHODS:
      Between May 1992 and December 2000, 37 patients with NVE and 16 patients with PVE
      underwent aortic valve replacement with homografts for infective endocarditis. In
      the two groups of patients the mean age was 57 and 61 years and 38% and 50% were
      in NYHA functional class IV or V. At the time of surgery, 28 patients had gross
      vegetations, 23 single or multiple abscess cavities, 3 ventricular septal
      perforations, and 9 mitral valve endocarditis. Homograft insertion was performed
      in a subcoronary position in 47 cases and as a root replacement in 6 cases. In 21
      cases associated surgical procedures were also performed. RESULTS: Follow-up was
      94% complete at a mean of 56 months after valve replacement. There were 1
      hospital and 7 delayed deaths; the actuarial survival at 5 years was 85.5 +/- 6%
      for NVE and 80.8 +/- 10% for PVE. Endocarditis recurred early in 2 cases (both
      with fungal infection) and late in 3 cases with an endocarditis-free 5-year
      period of 87.1 +/- 5%. Delayed echocardiography demonstrated aortic incompetence
      classified as grade II in 40 cases and as grade III and IV in 2 cases. Thirty
      nine patients are in NYHA class I and 3 in class II or III. CONCLUSIONS: On the
      basis of our experience we can conclude that in case of acute endocarditis, if
      the results of surgery are to be optimized, an early diagnosis and aggressive
      medical therapy need to be combined with earlier surgical referral. In the
      presence of NVE without annular abscesses the likelihood of recurrent
      endocarditis is probably more likely to depend on the infective organism than on
      the type of valve implanted. Our results support the suggestion that in the
      presence of NVE with extensive annular abscesses or in case of PVE the homograft
      valve is the replacement device of choice.

PMID- 12187634
TI  - [Quantitative evaluation of functional mitral insufficiency in dilated
      cardiomyopathy: morphological and functional correlations].
AB  - BACKGROUND: Angiography and echo-color Doppler imaging are routinely used for the
      semiquantitative grading of functional mitral regurgitation (MR) in dilated
      cardiomyopathy. However, in case of severe regurgitation the results obtained
      using these two methods are discrepant. We propose quantitative echocardiographic
      evaluation and the related morphological parameters of remodeling of the
      ventricular and mitral apparatuses for the estimate of severe regurgitation.
      METHODS: Fifty-two patients with dilated cardiomyopathy and functional MR (28
      males, 24 females, ejection fraction < or = 40%) were evaluated by means of
      echocardiography for a total of 73 echocardiograms (basal and 21 at the sixth
      month). The echo measurements included the left ventricular end-diastolic and end
      systolic volumes, ejection fraction, area jet/left atrial area, diastolic and
      systolic mitral annulus areas and fractional contraction (MAC, %), systolic
      tenting area (TA, cm2, area enclosed between the annular plane and mitral
      leaflets), systolic tethering length (TL, cm, papillary tips and intervalvular
      fibrosa distance); quantitative Doppler (using the mitral and aortic stroke
      volumes) and PISA methods were averaged to calculate the regurgitant volume (RV,
      ml/beat), regurgitant fraction (RF, %), and effective regurgitant orifice (ERO,
      mm2). RESULTS: The strongest correlation with ERO, RV and RF was obtained with
      systolic TA (beta = 0.40, 0.67 and 0.60; SE 1.68, 1.56 and 1.38; p = 0.01, p =
      0.0001 and p = 0.0001, respectively) and MAC (beta = -0.33, -0.61 and -0.61; SE
      0.31, 0.31 and 1.49; p = 0.03, p = 0.0001 and p = 0.0001, respectively). We did
      not find any correlation with ejection fraction (p = NS). The following values
      were found to be indicative of severe functional MR: ERO > or = 40 mm2, RV > or =
      49 ml/beat, RF > or = 57%, MAC < or = 12.5%, TA > or = 7.7 cm2, and TL > or = 4.7
      cm. CONCLUSIONS: We did not find any significant correlation between the
      quantitative functional MR echo parameters and systolic dysfunction. The major
      determinants of ERO, RV and RF were the loss of MAC and larger systolic TAs.
      These parameters are significantly proportional to the severity of functional MR
      as assessed by the semiquantitative criteria commonly adopted in the clinical
      practice. We propose the values of ERO, RV, RF, TA, MAC and TL as indicative of
      severe functional MR.

PMID- 12187635
TI  - [Heart surgery interventions in chronic dialysis patients: short- and long-term
      results].
AB  - BACKGROUND: Chronic dialysis is a relevant risk factor for mortality and
      morbidity after cardiac surgery and cardiopulmonary bypass. The aim of this study
      was to evaluate the short- and long-term follow-up of patients in dialysis
      undergoing cardiac surgery. METHODS: We retrospectively reviewed 24 consecutive
      chronic hemodialysis adult patients (14 males, 10 females, mean age 63 +/- 12
      years) who, over a 10-year period, underwent operative cardiac procedures in our
      Institution. Prior to surgery the mean duration of dialysis was 55 +/- 18 months
      (minimum 3 months). Surgery included isolated coronary artery bypass grafting in
      18 patients, aortic valve replacement in 3, mitral valve replacement in 2, and
      double valve replacement (mitral and aortic) in 1. Sixteen operations were
      elective whereas 8 (33%) were performed in an emergency setting. RESULTS: Seven
      operative deaths occurred with an overall in-hospital mortality of 29%. Among the
      16 patients in whom surgery was elective, only 2 died. Five of the 8 patients
      submitted to emergency procedures died. Hence, the operative mortality in this
      subgroup of patients was 62% (p < 0.005). A low cardiac output and multiorgan
      failure due to pulmonary infection were the most important causes of death.
      However 75% of patients experienced some major postoperative complications. All
      survivors were followed up for 6 to 108 months (mean 33.7 +/- 29.5 months). The
      overall functional status was significantly improved. Survival at 1, 2 and 5
      years was 68, 63 and 45% respectively in coronary patients and 65, 58 and 42% in
      the overall study population. CONCLUSIONS: In dialysis-dependent patients major
      cardiac procedures can be carried out with an acceptable risk only in elective
      conditions even if the mortality is 4-5-fold higher than in the normal population
      and the life expectancy is similar to that of patients in chronic dialysis but
      without cardiac disease.

PMID- 12187636
TI  - [Cardiac myxoma: surgical results and 15-year clinical follow-up].
AB  - BACKGROUND: Among cardiac tumors myxoma is the most common benign neoplasm. The
      aim of this study was to review our Institution's 15-year experience with
      intracardiac myxoma. METHODS: From 1985 through 2001, 38 patients (22 males, 16
      females, mean age 57.06 +/- 11.1, range 32-74 years) underwent surgical resection
      of a cardiac myxoma at our Institution. The tumor was located in the left atrium
      in 29 patients (76.3%), in the right atrium in 8 patients (21%), and in the right
      ventricle in 1 patient (2.6%). The duration of symptoms prior to surgery ranged
      from 2 to 30 days. None of the patients had a familial myxoma. The surgical
      approach comprised complete wide excision in all patients. The incidence of
      delayed death, thromboembolic complications, valve degeneration, recurrence and
      reoperation were reviewed and the Kaplan-Meier survival curve was elaborated.
      RESULTS: There were no perioperative deaths. Three patients (7.9%) developed
      postoperative neurological sequelae: transient ischemic attacks in 2 patients
      (5.2%) and a stroke with persistent neurological deficit in 1 patient (2.6%). One
      patient (2.6%) required pacemaker implantation for complete atrioventricular
      block. An inferior myocardial infarction occurred in 1 patient (2.6%). During the
      follow-up, complete in 89.4% of the patients (34 out of 38 patients, mean 96.8 +/
      68.4 months, range 1-218 months), there were 2 (5.8%) non-cardiac related
      deaths. All the patients underwent clinical examination and echocardiography at
      regular intervals (1 year): no neurological event was observed during the follow
      up and 29 patients (90.6%) are in NYHA functional class I. At 15 years the event
      free rate is 85.2%. At 15 years the actuarial survival for the whole group is
      92%. CONCLUSIONS: At present, the diagnosis of myxoma is easy to make and two
      dimensional echocardiography plays a major role in this field. Surgery is the
      gold standard treatment and the clinical long-term results are excellent.

PMID- 12187637
TI  - [Sex differences in incidence of mortality after acute myocardial infarction].
AB  - BACKGROUND: Previous studies have indicated that the mortality after acute
      myocardial infarction (AMI) is higher among women than among men. However,
      whether this difference is attributable to the older age of the women studied or
      to the presence of other unfavorable prognostic factors remains unclear. METHODS:
      This retrospective study compares the clinical features, management and 30-day
      outcome in men and women from a consecutive, unselected series of 878 patients
      with AMI (225 women, 25.7%) who were admitted to the coronary care unit. The
      studied variables included demographic, history and risk factors, the ECG at the
      time of admission and treatment assignment. The analysis, both unadjusted as well
      as adjusted, was performed using multiple logistic regression. RESULTS: The
      overall mortality rate during hospitalization was 24.4% for women and 13.2% for
      men (p < 0.0001). Women were, on average, significantly older than men (71.6 vs
      62.3 years, p < 0.0001), had a higher prevalence of hypertension (58.2 vs 41.5%,
      p < 0.0001) and diabetes mellitus (33.7 vs 19.6%, p < 0.0001), were less
      frequently smokers (22.2 vs 52.3%, p < 0.0001) and waited longer resorting to the
      coronary care unit following the onset of symptoms (p < 0.005). Thrombolytic
      therapy was prescribed less often in women (19.1 vs 40.7%, p < 0.0001). Women had
      more mechanical complications than men (acute pulmonary edema, p < 0.0001;
      cardiogenic shock, p < 0.03). No significant difference was found between sexes
      regarding previous coronary events, the size and type of infarction, the ECG at
      the time of admission and arrhythmic or ischemic complications. After adjustment,
      female gender was not an independent predictor of mortality, following AMI.
      Mortality rates after AMI remained significantly higher for women than for men
      only among patients who had not received thrombolysis (odds ratio 1.90, 95%
      confidence interval 1.08-3.34, p < 0.03). CONCLUSIONS: Much of the increased post
      AMI mortality observed in women could be attributed to age, risk factors,
      comorbidity and other baseline characteristics. Female gender seems to be
      independently associated with a higher risk of death after AMI only among
      patients to whom thrombolytic therapy is not prescribed.

PMID- 12187638
TI  - [When is valve stenosis considered to be critical?].
AB  - The aim of the present paper was to determine why mitral stenosis is considered
      critical when the valve area is < or = 1 cm2, and an aortic stenosis when the
      valve area is < or = 0.8 cm2. An area-resistance curve was drawn for 490 patients
      with mitral stenosis, and for 525 with aortic stenosis. All points lie on the
      same curve, but mitral stenosis fell in the low resistance, while aortic stenosis
      fell in the high resistance section. Critical stenosis respectively begins and
      ends at the point of curve inflection, i.e. where the valve resistance increases
      or decreases sharply.

PMID- 12187639
TI  - [Proarrhythmic effects of propafenone in a woman with hepatopathy: is it always a
      simple drug in clinical practice?].
AB  - A 65-year-old woman with a history of alcoholic liver disease and presenting with
      fever and vomiting was admitted to an internal medicine unit. In view of recent
      atrial fibrillation with inadequate heart rate control, digoxin and propafenone
      were included in the therapeutic regimen. After a few days sinus rhythm was
      restored but suddenly ventricular arrhythmias with the characteristics of a non
      responsive electrical storm arose shortly following the appearance of clinical
      symptoms of drug intoxication.

PMID- 12187640
TI  - [Acute dysfunction of Liotta mitral bioprosthesis 8 years after implantation].
AB  - The low-profile porcine bioprosthesis Liotta was introduced in clinical practice
      in order to reduce the potential complications related to excessive protrusion of
      the stent into the left ventricle after mitral valve replacement. Otherwise the
      particular design of this device seems to determine an excessive stress at the
      commissural level. We describe a case of acute dysfunction of the Liotta
      bioprosthesis secondary to commissural tear associated with minimal
      calcifications that required a reoperation in emergency.

PMID- 12187641
TI  - Theoretical models of wound healing: past successes and future challenges.
AB  - The complex biology of wound healing is an area in which theoretical modelling
      has already made a significant impact. In this review article, the authors
      describe the key features of wound healing biology, divided into four components:
      epidermal wound healing, remodelling of the dermal extracellular matrix, wound
      contraction, and angiogenesis. Within each of these categories, previous
      modelling work is described, and the authors identify what they regard as the
      main challenges for future theoretical work.

PMID- 12187642
TI  - Multiplicative genetic effects in scrapie disease susceptibility.
AB  - Despite experimental evidence that scrapie is an infectious disease of sheep,
      variations of the occurrence of the natural disease suggest an influence of host
      genetic factors. It has been established that the genetic polymorphism of the
      prion protein (PrP) gene is correlated to the incidence of scrapie and to the
      survival time: five polymorphisms have been described by variations at amino-acid
      codons 136, 154 and 171. In this paper we study the effect on scrapie
      susceptibility of the pairing of the five allelic variants known to exist: we
      show that scrapie susceptibility is given by the produce of the elementary
      allelic factors. This first well-documented evidence of a multiplicative property
      of genetic risk factors could give hints on the underlying mechanisms of prion
      induced neurodegenerative diseases.

PMID- 12187643
TI  - Morphogenesis of fingers and branched organs: how collagen and fibroblasts break
      the symmetry of growing biological tissue.
AB  - Understanding the growth of branching organs is an important scientific
      endeavour. It has crucial applications, from saving premature newborns, to
      repairing or even regenerating organs. Despite differences in timing and shape,
      branching morphogenesis of all branching organs or glands (lung, kidney,
      salivary, lachrymal, mammary glands, sebaceous and sweat glands, prostate, guts
      papillae etc.) is similar: an epithelial sheet of cells, forming a 2D layer,
      penetrates into a 3D mass of mesenchymal cells. Inside the epithelium, a lumen is
      filled with fluid. As the epithelium grows, it evolves into a branched structure.
      The pattern of branches is in some cases stereotypic, deterministic, and it has
      memory effects. We present a simple line of reasoning that predicts that viscous
      fingering of biological tissue will exhibit all of these features. The line of
      reasoning is based on the idea that surface tension selects the shape of a
      growing branch, as is well known in the context of moving boundary problems,
      except that in this case, the surface is akin to a liquid-crystal. The anisotropy
      of the surface tension comes from a symmetry breaking by collagen and
      fibroblasts. The equilibrium shape of the corresponding boundary is that of an
      actual fingertip, and the out-of-equilibrium shape is that of branched organs,
      such as the lung.

PMID- 12187644
TI  - [Human development and log-periodic law].
AB  - We suggest applying the log-periodic law formerly used to describe various crisis
      phenomena, in biology (evolutionary leaps), inorganic systems (earthquakes),
      societies and economy (economic crisis, market crashes) to the various steps of
      human ontogeny. We find a statistically significant agreement between this model
      and the data.

PMID- 12187645
TI  - Does sulphide detoxication occur in the gills of the hydrothermal vent shrimp,
      Rimicaris exoculata?
AB  - Ultrastructural observations of the gills of the hydrothermal vent shrimp
      Rimicaris exoculata reveal that the epithelial cells contain numerous
      mitochondria clustered around unusual organelles (diameter of 0.7 to 2.5 microns)
      containing membrane stacks. These organelles were termed sulphide-oxidising
      bodies (SOBs) by structural analogy with organelles observed in the tissues of
      species adapted to sulphide-rich environments. Moreover, in the gills of R.
      exoculata, mitochondria display numerous electron-dense granules in their stroma.
      Such ultrastructural features suggest that sulphide detoxication may probably
      occur in the gills of R. exoculata. Comparable structures were also described in
      the gills of other hydrothermal vent species, as the alvinellid Pompeii worms
      that, as R. exoculata, are housing ectosymbiotic bacteria.

PMID- 12187646
TI  - [Decomposition and nitrogen dynamics of wheat residues and impact on wheat growth
      stages].
AB  - N mineralisation and immobilisation were quantified in field conditions in the
      presence or in the absence of wheat residues. The incubation study was conducted
      in cylinders placed in microplots (no plants were grown in cylinders), and the
      rest of each microplot was sowed with the wheat crop (Triticum durum var. Massa).
      N mineralisation and immobilisation depend on the presence or the absence of
      wheat residues. In absence of residues, a linear model of regression was
      developed to follow the clear nitrogen mineralisation at different soil levels.
      Nitrogen mineralisation (mg kg-1), during the five months of wheat development,
      showed the following decreasing order: 0-15 cm (132.6) > 15-30 cm (120.6) > 30-45
      cm (91.3). The mineralisation rate was 24.1, 22.9 and 18.9 mg kg-1 d-1 for 0-15,
      15-30 and 30-45 cm levels, respectively. The supply of wheat residues resulted in
      a five months N immobilisation process. At level 0-15 cm the immobilisation (mg
      kg-1) showed the following decreasing order: (61.6) > (46.4) > (30.0) for the
      supply of wheat residues at seeding time, and 15 and 30 d before seeding
      respectively. At the other levels, the same decreasing order was recorded. The
      supply of 8 t ha-1 of wheat residues at seeding time, and 15 or 30 d before
      seeding, decreased the dry matter yield and N accumulation in wheat crop. In
      consequence, there was no synchronism between the nitrogen liberated by wheat
      residues decomposition and the wheat growth.

PMID- 12187647
TI  - [Biology and population dynamics of Porcellionides sexfasciatus (Crustacea,
      Isopoda, Oniscidea)].
AB  - The biology and the population dynamics of Porcellionides sexfasciatus Budde-Lund
      (1879) were studied on a field and carried out at Garat Naam (Kasserine, Tunisia)
      from July 1996 to June 1998. The reproduction exhibited a seasonal pattern
      extending from February/March to October/November. The juveniles appeared in the
      population from April to November. Size frequency distributions were analysed and
      14 cohorts were recognised during the sampling period. Six cohorts were
      identified at the first sampling and eight new ones on the other samplings. Among
      these latter cohorts, three were tracked till they disappeared. Minimum average
      length of new cohorts ranged from 3.07 +/- 0.35 mm to 3.47 +/- 0.2 mm. Maximum
      average length of cohorts was 10.42 mm. P. sexfasciatus is a semi-annual species
      (females producing two or three broods per year), with iteroparous and amphogenes
      females (females reproducing twice or more in their life and producing both males
      and females), and bivoltine life cycle (two generations per year). The females
      are able to produce two broods, in the laboratory, without new mating. Fecundity
      and fertility, corresponding to the number of eggs or embryos per brood, appeared
      positively correlated with females' size. Although oscillating throughout the
      year, the sex ratio was often in equilibrium.

PMID- 12187648
TI  - [Cupressus dupreziana A. Camus: distribution, decline and regeneration on the
      Tassili n'Ajjer, central Sahara].
AB  - As soon as it was first discovered in 1924, on the heights of the Tassili
      n'Ajjer, Cupressus dupreziana (A. Camus) was declared an endangered species. The
      few ancient trees to be seen in the beds of wadis gave reason to suppose that
      they were isolated individuals left behind from a forest that had flourished in a
      damper climate. Attempts at a census of the trees were made on a number of
      occasions, the fullest, in 1972, reporting a total of 230 living specimens. The
      revision of this inventory between 1997 and 2001 has now enabled us to draw the
      boundaries of the present range of this species, to assess its rate of decline
      over the last three decades and, for the first time, to record some regeneration,
      with the presence of new, young trees.

PMID- 12187649
TI  - [Influence of vegetation on the accumulation of peat in southern Quebec].
AB  - Mirabel bog (southern Quebec) was studied with the aim of specifying the past
      influence of local vegetation on peat accumulation. This influence was
      essentially translated by the reduction of minerotrophic inputs and peat
      accumulation induced by the highering of the peatland surface. Extremely rich
      initial conditions allow to explain the very high accumulations of the beginning
      of the Holocene, observed in various plant communities, among which Larix forests
      with ferns and Carex without modern analogues. Moreover, the structure (forest
      density) and the composition (dominance of Cyperaceae or Ericaceae) of these
      communities have locally controlled the dynamic of peat accumulation. These
      results point out the interest of the confrontation between palynological and
      macrofossil data and the spatialisation of palaeoecological studies.

PMID- 12187650
TI  - [Needs and resources: postgraduate education for psychiatrists].

PMID- 12187651
TI  - [Needs of young psychiatrists as seen by teachers].

PMID- 12187652
TI  - [Post-graduate educational programs in other countries: Comparison with the
      Japanese programs].

PMID- 12187653
TI  - [Art therapy and psychopathology].

PMID- 12187654
TI  - [Diagnosis and therapy of sleep disorders in neuropsychiatric diseases].

PMID- 12187655
TI  - [Near-infrared optical imaging of human brain function--a novel approach to the
      brain and the mind].
AB  - Near-infrared spectroscopy (NIRS) can measure changes in the hemoglobin
      oxygenation state in the human brain. NIRS has been oriented toward use for
      clinical monitoring of tissue oxygenation. However, we and others have recently
      demonstrated that NIRS also has the potential for neuroimaging. NIRS instruments,
      which use continuous wave light (CW) as a light source, are now commercially
      available. These CW-type NIRS instruments have high temporal resolution (less
      than 1 second) and allow long-term and continuous measurements, though they do
      not provide absolute values of changes in hemoglobin concentrations. In contrast,
      time-resolved spectroscopy (TRS), which uses short pulsed laser diodes as light
      sources, makes quantification possible. Quantification is necessary for the
      imaging of brain activity. Topographical images can be obtained by the use of our
      recently developed 64-channel time-resolved optical tomographic imaging system
      (optical CT) or by combining the 1 channel TRS instrument with the multichannel
      CW-type NIRS instrument. NIRS is completely non-invasive and does not require
      strict motion restriction during measurements unlike PET and fMRI. It is, thus,
      expected that NIRS will open a window into brain physiology in subjects who are
      difficult to examine with PET and fMRI such as children, the elderly, and
      patients with psychoneurological problems.

PMID- 12187656
TI  - [Macroscopic indices of psychiatric hospital functions: evaluation based on data
      of remaining hospitalized patients].
AB  - In recent years, mental health administration in Japan has been changing its
      orientation from institutional care to community-based care. For this reason, we
      need new macroscopic indices evaluating psychiatric hospital functions. The most
      notable indices are data of the remaining hospitalized patients. In this paper,
      we discuss the macroscopic indices evaluating psychiatric hospital functions
      focusing on the data of the remaining hospitalized patients. The data are based
      on a survey of the number of monthly discharged patients who had been admitted to
      1,617 psychiatric hospitals in the month of June 1998. The result shows that 1.
      70.4% of admitted patients are discharged to communities within a year, 2. 18.3%
      of patients remain hospitalized one year after admission, and 3. 50% of admitted
      patients are discharged within 74.2 days. Examination of these data showed it is
      very useful to evaluate psychiatric hospital functions by categorizing
      psychiatric hospitals based on the rate of patients remaining hospitalized one
      year after admission. We also found that "the rate of admissions discharged to
      communities within a year", "the rate of patients remaining hospitalized after
      one year", "transition in the rate of patients remaining hospitalized", and "the
      number of days until 50% of admitted patients are discharged" can be used as
      effective and practical indices evaluating psychiatric hospital functions.

PMID- 12187657
TI  - [Clinical study of depression accompanying diabetes mellitus].
AB  - The appropriate management of chronic diseases is important to ensure a high
      quality of life. In particular, depression has been reported to occasionally
      accompany diabetes mellitus. Here, we investigated depression onset in
      individuals with diabetes mellitus. Subjects were outpatients with a clinical
      diagnosis of depression in combination with diabetes mellitus between August 1,
      1998 and September 30, 1998 of the psychiatry clinic of Jichi Medical School. Of
      34 individuals (20 males, 14 females) included in the preliminary investigation,
      22 were interviewed. We investigated the social demographic background, the
      treatment, family history of depression and diabetes mellitus, and measured the
      Hamilton's Rating Scale for Depression and the value of HbA1c. The overall
      male/female ratio was 13/9, indicating that this pattern of disease onset was
      more common in males than in females. The Hamilton's Rating Scale for Depression
      correlated closely with the percentage of patients being treated with insulin.
      Furthermore, the timing of the diagnosis of these two diseases correlated closely
      with each other. The ratio of males to females suggested that the different
      gender roles and lifestyles and the biological bases of these differences may
      play roles in the onset of depression among diabetic patients. Moreover, as more
      patients with insulin dependence developed depression than patients without
      insulin, insulin was implicated in the onset of depression. Furthermore, as the
      onset of the two diseases correlated closely with one another, the onset of one
      disease may have hastened the onset of the other.

PMID- 12187658
TI  - [Progress in the field of hematology in the last 100 years].

PMID- 12187659
TI  - [Progress in the field of hematology in the last 100 years: Hematopoiesis and
      hematopoietic stem cell].

PMID- 12187660
TI  - [Progress in the field of hematology in the last 100 years: Radiation injuries
      and hematologic malignancies].

PMID- 12187661
TI  - [Progress in the field of hematology in the last 100 years: Erythropoietin].

PMID- 12187662
TI  - [Progress in the field of hematology in the last 100 years: Discovery of
      granulocyte colony-stimulating factor and the clinical application].

PMID- 12187663
TI  - [Progress in the field of hematology in the last 100 years: Cytogenetics].

PMID- 12187664
TI  - [Progress in the field of hematology in the last 100 years: Immunotherapy].

PMID- 12187665
TI  - [Progress in the field of hematology in the last 100 years: Gene therapy].

PMID- 12187666
TI  - [Progress in the field of hematology in the last 100 years: From chemotherapy to
      target-based therapy for hematologic malignancies].

PMID- 12187667
TI  - [Progress in the field of hematology in the last 100 years: Trends in diagnosis
      of malignant lymphoma based on pathology].

PMID- 12187668
TI  - [Progress in the field of hematology in the last 100 years: Hematopoietic stem
      cell transplantation].

PMID- 12187669
TI  - [Progress in the field of hematology in the last 100 years: Blood transfusion].

PMID- 12187670
TI  - [Contribution of Japanese researchers to progress in the field of hematology in
      the last 100 years: Porphyria/congenital heme synthetase deficiency].

PMID- 12187671
TI  - [Contribution of Japanese researchers to progress in the field of hematology in
      the last 100 years: Hereditary hemolytic anemia].

PMID- 12187673
TI  - [Contribution of Japanese researchers to progress in the field of hematology:
      Chediak-Higashi syndrome].

PMID- 12187672
TI  - [Contribution of Japanese researchers to progress in the field of hematology in
      the last 100 years: Pathogenic gene in paroxysmal nocturnal hemoglobinuria].

PMID- 12187674
TI  - [Contribution of Japanese researchers to progress in the field of hematology in
      the last 100 years: Genes involved in the chromosomal translocation].

PMID- 12187675
TI  - [Contribution of Japanese researchers to progress in the field of hematology in
      the last 100 years: Adult T-cell leukemia-lymphoma].

PMID- 12187676
TI  - [Contribution of Japanese researchers to progress in the field of hematology in
      the last 100 years: Kikuchi's disease].

PMID- 12187677
TI  - [Contribution of Japanese researchers to progress in the field of hematology in
      the last 100 years: Von Willebrand disease].

PMID- 12187678
TI  - [Contribution of Japanese researchers to progress in the field of hematology in
      the last 100 years: Congenital deficiency of alpha2-plasmin inhibitor].

PMID- 12187679
TI  - [Progress in the field of hematology in the last 100 years: Medical history of
      Aplastic anemia].

PMID- 12187680
TI  - [Progress in the field of hematology in the last 100 years: Medical history of
      hypochromic anemia].

PMID- 12187681
TI  - [Progress in the field of hematology in the last 100 years: Medical history of
      paroxysmal nocturnal hemoglobinuria].

PMID- 12187683
TI  - [Progress in the field of hematology in the last 100 years: Medical history of
      chronic myelogenous leukemia].

PMID- 12187682
TI  - [Progress in the field of hematology in the last 100 years: Medical history of
      acute leukemia].

PMID- 12187684
TI  - [Progress in research on myelodysplastic syndrome in the last 100 years].

PMID- 12187685
TI  - [History of research on malignant lymphoma].

PMID- 12187686
TI  - [Progress in the field of hematology in the last 100 years: Medical history of
      multiple myeloma].

PMID- 12187687
TI  - [Progress in the field of hematology in the last 100 years: Medical history of
      thrombocytopathy].

PMID- 12187688
TI  - [Progress in the field of hematology in the last 100 years: Medical history of
      thrombosis].

PMID- 12187689
TI  - [Progress in the field of hematology in the last 100 years: Medical history of
      blood coagulation disorder].

PMID- 12187690
TI  - [Hematology in the twentieth century and prospects for the twenty first
      century(discussion)].

PMID- 12187691
TI  - [Progress in the field of hematology in the last 100 years: Clinical guidelines
      for disseminated intravascular coagulation].

PMID- 12187692
TI  - [Progress in the field of hematology in the last 100 years: Clinical guidelines
      for irradiation of blood to prevent graft-versus-host disease following blood
      transfusion].

PMID- 12187693
TI  - [Progress in the field of hematology in the last 100 years: Clinical guidelines
      for therapeutic administration of granulocyte-colony stimulating factor].

PMID- 12187694
TI  - [Recurrent spontaneous bacterial peritonitis in a patient with liver damage
      caused by chronic graft versus host disease].

PMID- 12187695
TI  - [HTLV-1 associated dermatomyositis].

PMID- 12187696
TI  - [Cervical aortic arch complicated with thoracic aortic aneurysms that occurred
      two times].

PMID- 12187697
TI  - [Mushroom poisoning whose symptoms were relevant to the amount of alcohol taken].

PMID- 12187698
TI  - [Ulcerative colitis developed after acute exacerbation of chronic hepatitis B].

PMID- 12187699
TI  - [Budd-Chiari syndrome incidentally found by an abnormal shadow on chest X-ray].

PMID- 12187700
TI  - [Histopathological diagnosis of opportunistic infection].
AB  - The histopathological diagnosis of infectious diseases has definite and
      inevitable roles not only in identifying the appropriate treatment for the
      infected patient but also in protecting society from unnecessary risks of
      pathogen transmission and from exposure to biohazards. The potential for
      opportunistic infection has been increasing, in response to the gradual increase
      of aged and immunocompromised patients. Globalization of the world has promoted
      importation of non-domestic infectious diseases. This article reviews the
      following points. These include 1) the modes of defense mechanisms against
      pathogens (neutrophils vs. T-lymphocytes vs. antibodies), 2) epidemiologic
      aspects of opportunistic infection, including intrinsic, exogenous and imported
      routes of infection, 3) histopathological features of bacterial pneumonia, 4)
      immunohistochemical demonstration of pathogens on routine paraffin sections,
      using commercially available antibodies or patient sera, 5) opportunistic
      infection in immunosuppressive states, such as AIDS, hematopoietic stem cell
      transplantation and other special conditions, and 6) the pathologists' function
      in the prevention of nosocomial (hospital-acquired) infection with MRSA and
      tuberculous bacilli. Pathologists must realize the importance of correct and
      prompt histopathological diagnosis of a wide variety of infectious diseases in
      both immunocompetent and immunocompromised patients.

PMID- 12187702
TI  - [Medical supports for the diagnosis of infectious diseases; the role and
      responsibilities of clinical pathologist and microbiology technologist. Acute
      purulent meningitis; the position of the technologists in microbiology
      laboratory].
AB  - The features and limitations of microbiology processes for the diagnosis of
      bacterial meningitis were summarized. Requests for physicians were also
      emphasized. The microbiology laboratory should be responsible for providing
      highly reliable and concordant data with a variety of clinical settings.
      Technologists in a microbiology laboratory should perform following subjects: i)
      Direct smear examination: Presumptive identification by the observers with
      abundant experience and sufficient training. ii) Rapid bacterial antigen
      detection tests: Active utilize alone in combination with the direct microscopy.
      iii) Culture: Cost effective utilize for appropriate media and culture condition
      based on the bacteriological statistics. Report with bacteriological
      interpretations and with additional proper comments, if necessary. iv)
      Antimicrobial susceptibility tests: Determination of penicillin resistance among
      the strains of penicillin-resistant or-intermediate Streptococcus pneumoniae (PI
      or PRSP) should be confirmed by MIC procedures; Detection of beta-lactamase
      producing Haemophilus influenzae (BLP) could detect by beta-lactamase tests, but
      not clearly identify for beta-lactamase-negative ampicillin-resistant isolates
      (BLNAR). In addition, a laboratory should provide appropriate information by
      using the accumulated routine clinical microbiology data, which may help to
      physicians in selecting an empiric therapy and to the microbiology technologists
      in processing the routine microbiology. In recent status, the most common
      organisms isolated from patients with bacterial meningitis continue to be S.
      pneumoniae and H. influenzae. Among S. pneumoniae strains, penicillin
      intermediate(PISP) and--resistant(PRSP) strains had exceeded 50%, and the strains
      of beta-lactamase producing H. influenzae (BLP) had decreased with less than 10%
      and beta-lactamase negative ampicillin-resistant strains (BLNAR) have increasing.
      To providing rapid and accurate results, a laboratory should require the clinical
      information, including patient's age, major presenting symptoms, and receive
      antimicrobials prior to specimen collection.

PMID- 12187703
TI  - [From the perspective of clinical laboratory physicians].
AB  - In this symposium, how clinical laboratory doctors can contribute to diagnosis
      and management of infectious diseases will be discussed. A case of community
      acquired pneumonia that was finally diagnosed as Legionella infection is
      presented, and the etiology and pathogenesis of pneumonia is discussed from the
      perspective of a clinical laboratory doctor. Community-acquired pneumonia (CAP)
      remains an important infectious disease, not only in developing countries but
      also in developed countries including Japan. Accumulating epidemiological data
      demonstrated that Streptococcus pneumonia remains a leading cause of CAP,
      followed by atypical pathogens, such as Legionella, Mycoplasma and Chlamydia.
      Recent progress in diagnostic methods has facilitated the rapid diagnosis of
      these infections by PCR and antigen detection. Especially, urinary antigen
      detection kits for S. pneumonia and L. pneumophila became available recently and
      these have proven to be convenient and reliable. Clinical laboratory doctors may
      contribute to the clinical side by providing these kinds of new information, such
      as epidemiology, diagnosis and antimicrobial chemotherapy. In addition,
      construction of reliable relationships between clinical doctors and clinical
      laboratory doctors may be prerequisite for efficient contribution of the
      laboratory side.

PMID- 12187701
TI  - [Laboratory logistics for infectious diseases--from clinical laboratory
      physicians].
AB  - The diagnosis of bacterial meningitis rests on examination of the CSF. The gross
      appearance of the fluid may be cloudy or turbid if the white cell count is
      elevated. Gram's staining should always be used in examining CSF, as it permits
      rapid and accurate identification of the etiologic agent in approximately 60 to
      90 percent of cases of bacterial meningitis. The CSF culture is positive in
      approximately 70 to 85 percent of patients with bacterial meningitis. Many other
      rapid diagnostic tests have been developed to aid in the diagnosis of bacterial
      meningitis when Gram's staining gives negative results. Nevertheless, newer
      techniques are more rapid and sensitive, postgraduate training in laboratory
      medicine should include basic clinical skills (Communication skills, physical
      examination and common laboratory procedures such as Gram's stain, Wright-Giemsa
      stain, etc.) and 24 hours on-call service system by laboratory physicians. It
      must not be focused solely on the sophistication of laboratory methods. We must
      notice that an increasing gap between the clinic and the laboratory. Current
      needs require us to make a major attempt to bridge this gap. We, laboratory
      physicians must modify our behavior effectively and accept the value and
      limitations of laboratory automation and information technology. We must work
      more closely with physicians and other health care professionals to establish a
      good collaborative partnership with them.

PMID- 12187704
TI  - [Community-acquired pneumonia--from medical technologist].
AB  - The main causative microorganisms of Community-acquired pneumonia are
      Streptococcus pneumoniae, Haemophilus influenzae, and Staphylococcus aureus.
      Especially the causative microorganisms affecting whole body basic disease,
      persons of advanced age, and alcoholic patients are Moraxella catarrhalis,
      Klebsiella pneumoniae, Pseudomonas aeruginosa, Candida spp., Cryptococcus spp.,
      Aspergillus spp., Pneumocystis carinii and anaerobic bacteria. Other
      microorganisms involved in epidemic disease, action condition (travel around hot
      springs etc.) and pet breeding environments are Mycoplasma pneumoniae, Legionella
      pnumophila, Chlamydia spp., respiratory syncytial virus, influenza virus, and
      adeno virus. We suggest methods of advancing the microscopic and microbiological
      examination and report, and quickly obtaining clinical information and extracting
      the clinical specimen. We also describe the inspection method for a case
      "Legionella pneumonia" that was discussed during this symposium.

PMID- 12187705
TI  - [Complicated urinary tract infections--from the perspective of the medical
      technologist].
AB  - We would like to propose re-establishment of the protocol for ordering a clinical
      microbiology laboratory test after a bedside screening test using urine reagent
      strip when urinary tract infection is suspected. Media for isolation shall be
      chosen by the clinical microbiology laboratory after checking turbidity and
      microscopic examination of the urine specimen. In cases of complicated urinary
      tract infections, quantitative culture should be performed to investigate changes
      in the number of microorganism to grasp condition of super infection. In such
      infections, there are many cases in which multiple microorganism growth including
      glucose non-fermenting gram-negative bacilli can be recognized. Therefore, it is
      necessary to inspect colonies on media as long as possible (24 hrs culture may be
      short in some cases). The protocol for microorganism identification and
      susceptibility test for such specimen varies in each laboratory, considering the
      Health Insurance Point System (reimbursement system by MHW). It is necessary to
      communicate with physicians and to refer to past results to proceed with the
      laboratory test properly. Therefore, a Certified Clinical Microbiology Medical
      Technologist is needed and the role played by such staff is important.

PMID- 12187706
TI  - [Future of laboratory informatics].
AB  - One of the major objectives of laboratory informatics is to develop database
      systems for test results. Such a database should be designed with the distinct
      objective of determining the normal range. To understand the normal range,
      however, more information on possible risk factors must be directly analyzed in
      population studies. In our population-based study, we found that carotid
      arteriosclerosis is independently correlated with LDL cholesterol level, HDL
      cholesterol level, body mass index, systolic blood pressure, and HbA1C (the
      Niigata Study). Through this study, we will be able to obtain normal ranges for
      some important laboratory tests.

PMID- 12187707
TI  - [Drug discovery based on genomic information].
AB  - Drug discovery is a continuum of the processes, i.e. identification of disease
      associated targets, screening of compound libraries, identification of leads and
      their optimization to drugs, preclinical and clinical drug development. Recent
      advances in genomic sciences will greatly reinforce processes such as early
      target identification and clinical researches. Particularly, exploitation of
      genomic information in clinical researches is expected to revolutionarily improve
      drug development and eventual clinical use. Ultimately, tailor-made medicine will
      provide us with great benefit in the near future therapy.

PMID- 12187708
TI  - [Future outlook for LAS, LIS].
AB  - In Japan, the application of LAS/LIS was started in some hospitals in the 1970's.
      Thereafter, these systems rapidly developed, becoming established in new national
      medical university hospitals in the late 1970's, referring to the system
      introduced in the central laboratory of each hospital. Currently, the LAS/LIS
      application system is employed in the central laboratory. In addition, this
      system provides diagnostic information based on laboratory data, responds to
      various questions regarding clinical examinations, develops strategies for
      controlling hospital infection using the infection control system, and provides
      information on the appropriate use of antimicrobial agents. In the future, this
      system may become even more useful. In this study, we reviewed the current status
      and issues of the mutual utilization of medical information among medical
      institutions to achieve further advances.

PMID- 12187709
TI  - [Determination of fractal dimension using digital nuclear image of lymphocyte].
AB  - Microscopic morphological findings in smeared and stained blood cells are
      difficult to be characterized quantitatively. However, a recent progress in
      digital image processing has been enabled to express some of these findings
      quantitatively. In this report, we propose the usefulness to determine "box"
      fractal dimension of nuclear image of lymphocyte. Fractal dimension was
      determined in digital 256-grayscale images of normal, atypical and leukemic
      lymphocytes by a box-counting method after extracting a nuclear image out of a
      cellular image, binalyzing and thinning it. The results suggest that fractal
      dimensions of nuclear images are mainly correlated with changes in chromatin
      appearance. Fractal dimension could be a useful quantitative parameter for
      cytological differentiation between normal and atypical lymphocytes.

PMID- 12187710
TI  - [Quality control for antimicrobial susceptibility test using correlation between
      MIC results].
AB  - The method of National Committee for Clinical Laboratory Standards (NCCLS) is
      widely used for the daily quality control of the antimicrobial susceptibility
      test. This method, however, cannot detect the accidental error, although it is
      useful to detect the systematic error in the examination. We developed a computer
      program using the correlation between the various antimicrobial susceptibility
      test results to detect an accidental error. The combinations of the MIC results
      determined for two antimicrobial agents which showed a high correlation
      coefficient (> or = 0.7), were selected from 98 bacterial species (2122 strains)
      isolated from January 2000 to December 2000 at Oita Medical University Hospital.
      Subsequently, a total of 127 combinations of antimicrobial agents for 13 species
      were selected on the basis of acceptable correlation ranges. Then, the method
      were verified with 666 strains (5753 combinations) isolated during the period of
      January to June, 2001. Twenty-six strains (47 combinations) were identified as an
      unexpected result, and the occurrence of error were confirmed in 3 strains (12
      combinations). These results suggest that this method which evaluated the
      correlation between MICs against different antimicrobial agents is applicable for
      the quality control of antimicrobial susceptibility testings.

PMID- 12187711
TI  - [A case of amelanotic melanoma of the nasal cavity].
AB  - A 68-year-old male visited Hospital A for treatment of epistaxis, his chief
      complaint. He was told that he had an easily-bleeding tumor in the nasal cavity.
      Based of biopsy, a diagnosis of amelanotic melanoma was made. Operation was
      performed for removal of the tumor. About 8 months after discharge, he visited
      Hospital B with complaints of lumbar pain and epistaxis. After biopsy at Hospital
      B, malignant lymphoma (diffuse large cell) was diagnosed, and the patient was
      referred to our hospital. On bone marrow puncture and biopsy, tumor cell
      infiltration was observed. Flow cytometric surface marker analysis revealed that
      these tumor cells were negative for CD45. Results of HE staining of the nasal
      cavity tumor were insufficient for diagnosis, and staining by
      immunohistochemistry was necessary to confirm the diagnosis. On
      immunohistochemical staining of the nasal cavity tumor tissue and bone marrow
      biopsy tissue, LCA, L26 and UCHL-1 were negative, and S-100 and HMB-45 positive.
      Recurrence of amelanotic melanoma accompanied by bone marrow infiltration was
      therefore diagnosed. The incidence of amelanotic melanoma with primary lesions in
      the nasal cavity is low. However, in making the diagnosis of a nasal cavity
      lesion, the possibility of such a melanoma should be kept in mind. In many cases,
      it is difficult to diagnose amelanotic melanoma with HE staining alone, and
      immunohistochemistry must be used.

PMID- 12187712
TI  - [Significance of the control serum measurement in infectious disease tests--a
      case of lot-to-lot variation of anti-HIV antibody assay kit].
AB  - We are using infectious disease test kits consisting of positive serum diluted
      with negative pooled serum (P-S) and positive control (P-C). In two anti-HIV
      antibody tests the results for both P-S and P-C fluctuated between positive and
      negative depending on the lot No. of the reagent. In Western blot tests carried
      out to confirm the tests, the P-C was found to be positive and the P-S tests were
      both inconclusive. We speculated that the P-S had very weak antibodies that
      reacted differently from patient samples. Manufacturers of such kits, however,
      must supply reagents with appropriate reactivity, so it is important that they be
      informed of inconsistencies that could invalidate cut-off values and lead to
      false-positives and false-negatives.

PMID- 12187713
TI  - [The diagnosis of brain death].

PMID- 12187714
TI  - [History of pituitary surgery].

PMID- 12187716
TI  - [Evaluation of cerebral hemodynamics with perfusion CT].
AB  - We report on the evaluation of cerebral ischemic lesions with perfusion CT.
      Cerebral blood flow (CBF), cerebral blood volume (CBV) and mean transit time
      (MTT) of 52 patients mostly with ischemic cerebrovascular disease were analysed
      using the box-modulation transfer function method with 30 ml of contrast medium
      intravenously injected at 5 ml/sec. CBF, CBV and MTT of the middle cerebral
      artery (MCA) territory were 43.5 +/- 4.6 ml/100 g/min, 1.9 +/- 0.2 ml/100 g and
      2.9 +/- 0.6 seconds at the unaffected side, and 37.7 +/- 7.3 ml/100 g/min, 2.1 +/
      0.3 ml/100 g, 3.7 +/- 0.9 seconds at the lesion side with stenosis or occlusion
      in the main MCA trunks or internal carotid artery, respectively. A statistically
      significant difference was shown in CBF and MTT values. Furthermore, there was a
      close correlation in CBF values of MCA territories between Xe-CT and perfusion CT
      (r = 0.645, n = 76, p < 0.0001). MTT showed a positive correlation with CBV in
      those subjects when MTT was below 4.1 seconds (r = 0.526, p < 0.0001, n = 83).
      MTT also showed a negative correlation with CBF in those patients when MTT
      indicated more than 4.1 seconds (r = 0.818, p < 0.001, n = 21). These results
      suggest that the progression of cerebral ischemia may be classified in 4 stages
      using perfusion CT. The stages are as follows: stage 0; normal CBF without
      prolonged MTT and increased CBV, stage 1; relatively increased CBV, stage 2;
      significantly prolonged MTT, and stage 3; significantly decreased CBF with
      prolonged MTT.

PMID- 12187715
TI  - [Wallerian degeneration demonstrated by MRI and functional outcome in patients
      suffering from supratentorial cerebrovascular disease].
AB  - An early diagnosis of the outcome of patients with cerebrovascular disease is
      important for selecting the optimal treatment strategy. The purpose of this study
      was to estimate the prognosis of Wallerian degeneration on MRI in stroke patients
      with hemiparesis. The subjects consisted of 87 stroke patients, 50 hemorrhagic
      patients and 37 ischemic patients, who were evaluated by MRI at 1 to 6,275 days
      after stroke onset. Among the 36 patients who were evaluated by consecutive MRI,
      161 films were obtained and analyzed. Wallerian degeneration was diagnosed when a
      small prolonged T 2 lesion was seen in the corticospinal tract of the brainstem
      on at least two contiguous slices. The atrophic rate of the midbrain was
      calculated as: (the area of the unaffected side of the midbrain--the area of the
      affected side of the midbrain)/2 x (the area of the unaffected side of the
      midbrain). The patients' ability to perform the activities of daily living was
      scored by the Barthel index (BI). Wallerian degeneration in the ipsilateral
      brainstem was seen for two to three months in 32 cases (37%) and in 58 films
      (36%) and disappeared about 3 years after the onset of stroke. Wallerian
      degeneration correlated with the BI scores from 2 to 6 months after stroke (p <
      0.05), although no relationship was observed at 7 months or later. From 2 to 6
      months after stroke, the shrinkage of the midbrain on MRI correlated with the BI
      scores (p < 0.001), although no relationship was observed at 7 months or later.
      It was therefore both Wallerian degeneration and a shrunken midbrain observed on
      MRIs, evaluated from 2 to 6 months after stroke were thus suggested to indicate a
      poor outcome in such patients.

PMID- 12187717
TI  - [Assessment of hemodynamics of meningioma with dynamic MR imaging].
AB  - Dynamic MR imaging provides hemodynamic information about normal and pathologic
      tissue of the brain. The purpose of our study was to evaluate the usefulness of
      dynamic MR imaging in the assessment of tumor vascularity and the tumor tissue
      blood flow of meningiomas. We studied 13 patients with meningiomas using dynamic
      spin-echo MR imaging. The histological subtypes of meningioma were confirmed by
      the examination of surgical specimens in all patients, and tumors were
      meningothelial in 9 cases, fibrous in 2, transitional in 1, and psammomatous in
      1. Serial images were obtained every 18-24 sec for 8 minutes and 30 seconds after
      rapid injection of gadolinium diethylenetriaminepentaacetic acid. Different
      parameters (time to peak, maximum of signal intensity and the washout ratio) were
      calculated directly from signal intensity curves. As an indicator of tumor
      vascularity, microvessel density was counted based on immunohistochemically
      stained sections and tumor tissue blood flow was measured using an xenon-CT
      system. The maximum of signal intensity corresponded to the tumor vascularity.
      With dynamic MR imaging, the time intensity curves (TI curves) were divided into
      two patterns; type 1 had a steep increase with a peak and type 2 had a slow
      increase to a peak followed by plateau. The maximum of signal intensity measured
      from TI curve of dynamic MR imaging correlated significantly with microvessel
      density (R2 = 0.840, p < 0.0001). Linear regression revealed a significant
      positive relation between the washout ratio and the tumor tissue blood flow in
      group showed type 1 on TI curve (R2 = 0.961, p < 0.001). There was also a
      significant negative correlation between the time to peak and the tumor tissue
      blood flow (R2 = 0.792, p < 0.01). We suggest that dynamic MR imaging is useful
      for evaluating hemodynamics of meningiomas.

PMID- 12187718
TI  - [Recurrent unipolar depression with 48-hour cycle and the state--dependent
      abnormal involuntary movements following right thalamic hemorrhage].
AB  - A 70-year-old woman was admitted because of depression and abnormal involuntary
      movements of her left extremities. Six months before the admission, she developed
      left hemiparesis caused by right thalamic hemorrhage. On neurological
      examination, she had mild motor and sensory hemiparesis on the left side. She
      showed recurrent depression each other days with a 48-hour cycle, and hemichorea
      hemiballism appeared in her left upper and lower extremities exclusively on the
      days with depressive phase. Her depressive symptoms were characterized by
      psychomotor retardation but not by feeling of suicide or guilty. She was then
      diagnosed as having a rapid cycler following the right thalamic hemorrhage. To
      our knowledge, it is extremely rare to see the state-dependent involuntary
      movements in patients with rapid cycler. The coexistence of post-stroke
      depression and hemichorea-hemiballism in the present patient may suggest that
      both disorders appear on the basis of the common pathophysiological mechanism
      such as dysfunction on frontal cortico-basal ganglia-thalamo-cortical loops.

PMID- 12187719
TI  - [A case of topographic disorientation without right occipital lesion].
AB  - A 73-year-old right-handed man developed topographical disorientation, left
      homonymous hemiianopsia, left visuospatial neglect and mild visual memory
      disturbance following the right hemispheric infarction. The visual agnosia is
      very similar to agnosia for streets because he could not identify familiar
      buildings and streets even though he could remember their way. He did not have
      prosopagnosia. His brain MRI demonstrated infarction at the right anterior
      choroidal artery area, including right thalamus, caudate tail and optic
      radiation. SPECT showed the mild decrease of rCBF at the right temporoparietal
      cortex. His topographic disorientation faded and finally disappeared about 3
      weeks after its onset. Our case is atypical because of sparing the posterior part
      of the right parahippocampal gyrus where plays an important role in the
      development of agnosia for streets.

PMID- 12187720
TI  - [A case of neuralgic amyotrophy manifesting bilateral anterior interosseous nerve
      syndrome].
AB  - A 49-year-old woman acutely developed severe bilateral shoulder pain followed by
      weakness of the right shoulder girdle muscles. Within a few days, an inability to
      flex the terminal phalanges of the bilateral thumbs and index fingers emerged.
      Neurologic examination 1 month after the onset of symptoms showed atrophy of the
      right shoulder girdle muscles and mild decreased cutaneous sensation in the
      distribution of the right axillary nerve. Needle electromyography examination at
      this time showed fibrillation potentials in the right deltoid and bilateral
      flexor pollicus longus muscles. Recruitment of the right deltoid, supra- and
      infraspinatus muscles was reduced. Motor unit potentials in these muscles were of
      normal configuration. Nerve conduction studies in the upper limb were normal. She
      was diagnosed as neuralgic amyotrophy with bilateral anterior interosseous nerve
      syndrome. 4 months later, the muscles innervated by the bilateral anterior
      interosseous nerve improved in the muscle strength. Clinical features of this
      case were compatible with a mononeuropathy multiplex form of neuralgic amyotrophy
      associated with an autoimmune etiology. We think this case is important for
      speculating the pathogenesis of neuralgic amyotrophy. This case reminds us that
      patients with neuralgic amyotrophy sometimes demonstrate anterior interosseous
      nerve syndrome and most patients manifesting anterior interosseous nerve syndrome
      are patients with neuralgic amyotrophy.

PMID- 12187721
TI  - [Fetal germinal matrix and intraventricular hemorrhage associated with
      periventricular leukomalacia].
AB  - Subependymal germinal matrix hemorrhage with intraventricular hemorrhage(SEIVH)
      is a common complication associated with delivery in preterm neonates but has
      rarely been observed in the fetus. We report a fetus with SEIVH, hydrocephalus
      and periventricular leukomalacia(PVL). Although this fetus had uneventful
      prenatal periods, transabdominal ultrasound examination(US) at 33 weeks of
      pregnancy revealed SEIVH and hydrocephalus, and MRI at 36 weeks did associated
      PVL. While no events reported that could explain the onset of SEIVH, PVL was
      considered to be the results of anoxic events associated with SEIVH. In addition
      to US, information provided by fetal MRI, especially T 2-weighted image, permits
      a better understanding of the pathophysiology of fetal SEIVH with PVL.

PMID- 12187722
TI  - [A sporadic case of late-onset familial amyloid polyneuropathy type I
      (transthyretin Met 30-associated familial amyloid polyneuropathy) inborn habitant
      of Ehime prefecture].
AB  - We reported a 62-year-old man of late-onset familial amyloid polyneuropathy type
      I(transthyretin Met 30-associated familial amyloid polyneuropathy) from Ehime
      Prefecture. There was no family history related to endemic Japanese foci (Nagano
      and Kumamoto foci). He demonstrated paraesthesia in the legs and mild autonomic
      symptoms at the age of 52. These symptoms gradually developed. Analysis of the
      transthyretin gene from his leucocytes demonstrated he had Met 30 transthyretin
      mutation. Therefore, he was diagnosed with late-onset familial amyloid
      polyneuropathy type I(FAP 1). In some families, asymptomatic carriers with the
      mutant transthyretin gene were diagnosed. In early stage, this patient's
      polyneuropathy and autonomic nervous system dysfunction were less serious than
      those of FAP 1 patients from endemic Japanese foci. These symptoms of this
      patient was slowly progressive. He hoped liver transplantation (brain death or
      living-related) treatment if possible. Now he became 68-year-old and bed-ridden.

PMID- 12187723
TI  - [Microcystic meningioma associated with a seizure attack].

PMID- 12187724
TI  - [Hypertrophic pachymeningitis carcinomtosa in a patient with the breast cancer].

PMID- 12187725
TI  - [Vascular dementia with a suspicion of Alzheimer's disease in early
      stage(clinical conference)].

PMID- 12187726
TI  - [Surgery for entrapment neuropathies].

PMID- 12187727
TI  - [Relationship of direction of drainage tube and recurrence in chronic subdural
      hematoma].
AB  - The favorable effect of burr hole irrigation and closed drainage system has been
      reported in the treatment of chronic subdural hematoma (CSH). After analyzing the
      relationship of the direction of the drainage tube and recurrence, we have
      suggested that the residual air after surgery night be important as one of the
      factors causing recurrence. The present study included 128 chronic subdural
      hematomas in 102 patients who had been treated in our institute between January,
      1996 and October, 2000. We attempted to place the tip of the external drain at
      the occipital side within the hematoma cavity between January, 1996 and December,
      1998 (occipital drainage group), while we tried to insert the tip of the external
      drain at the frontal side using an endoscope between January, 1999 and October,
      2000 (frontal drainage group). We focused on the residual air on CT, the
      direction of the drainage, recurrence of the hematoma and the size of the
      hematoma. Some statistical analyses were conducted using these factors. The
      recurrence rate was slightly lower in the frontal drainage group than that in
      occipital drainage group. There was no difference in the residual rate of air
      immediately after the surgery on CT and the recurrence rate between the 2 groups.
      However, the interval preceding the recurrence was statistically significantly
      longer in the frontal drainage group. A higher rate of recurrence was noted for
      cases in which the volume of hematoma was more than 70 ml. The residual rate of
      air 1 week after surgery was significantly higher in the recurrent group than in
      non-recurrent group. In this study, it is demonstrated that a long-standing
      residual of air after surgery is one of the causes of the recurrence of CSH. We
      must contrive to reduce the residual air after surgery for the treatment of CSH.

PMID- 12187728
TI  - [Observation of statistics of screening for unruptured cerebral aneurysms in
      Tochigi prefecture].
AB  - Screening for unruptured cerebral aneurysms (UCAs) using magnetic resonance
      imaging (MRI) and angiography (MRA) is prevalent in Japan. To reveal the
      prevalence of UCAs found during screening, we collected data of the results in
      1999, in Tochigi prefecture. In the prefecture, of which the population was about
      2 million, 26 institutions had been established in 1999, and 5,222 persons had
      been screened. These corresponded to 0.26% of all inhabitants of Tochigi
      prefecture. Of the 26 institutions, 24 cooperated in this study, and data was
      collected for 4,961 persons. We investigated the prevalence of UCAs, and compared
      it with that of subarachnoid hemorrhage (SAH) in Japan using the existing
      statistics. The UCAs were found in 143 (2.9%) of the 4,961 cases, 69 men and 74
      women, with a mean age of 59.2 years. The prevalence of UCAs at screening and the
      prevalence of SAH in Japan co-relate in that this prevalence increases with age
      in both UCAs and SAH. However, after the age of 75, the provalence of SAH
      decreases. People found with UCAs at screening were mainly in their 50's, but the
      member of those found with SAH increased gradually after that age. The rate of
      screening of women was lower than that of men, although both the prevalence of
      UCAs at screening and SAH of women is higher than that of men. We recommend that
      middle-aged persons, in their 40's and older, should request screening for UCAs.

PMID- 12187729
TI  - [Clinical analysis of pediatric shunt catheter fracture].
AB  - Between 1985 and 1998, 415 shunt dysfunctions occurred at Kobe Children's
      Hospital. The main reasons for shunt revision were obstruction of the catheter,
      shunt infection, and shunt disconnection. This report presents an analysis of 35
      patients (36 cases) who underwent a ventriculoperitoneal (VP) shunt revision
      because of shunt catheter fracture. All patients were less than 18 years old. We
      researched their age at the time of revision, site of disruption, postoperative
      period, shunt system, clinical symptoms, and other factors. The mechanical
      aspects of shunt catheter fracture are also discussed in this report. The peak
      time of shunt catheter fracture was the time when children were growing up and
      were entering elementary school. In other words, when their height was increasing
      rapidly. At that time, the distal catheter is subjected to traction between the
      valve and the abdomen at the site of insertion in either the upper or lower
      direction. However, physical examination of the shunt catheter showed normal
      range. Additional contributory factors were chronic stimulation at the occipital
      bone, clavium bone, and costal arch, while movement of the neck and body rotation
      also caused shunt catheter fracture. These factors all originated from shearing
      strain at the shunt catheter. We look forward to the introduction of a stronger
      shunt catheter, because surgical repair time must be minimized to protect the
      child's mental development. In addition, shearing strain at the shunt catheter
      needs special attention.

PMID- 12187730
TI  - [A case of subarachnoid hemorrhage associated with spontaneous intracranial
      hypotension].
AB  - Cerebrospinal fluid (CSF) leakage has recently been documented in most patients,
      as the main cause of spontaneous intracranial hypotension (SIH). No cases of SIH
      accompanying an episode of subarachnoid hemorrhage (SAH) has yet been reported
      and, to the best of our knowledge, this is the first report of a patient, who
      developed SAH during his clinical course of SIH. SAH was cured completely by
      surgical intervention. A 57-year-old man, with a history of a sustained postural
      headache, suffered the sudden onset of severe nuchal pain. SAH in the basal
      cistern, together with the finding of bilateral subdural fluid retention were
      verified by CT. Angiogram showed no vascular abnormalities of cerebral or
      cervical vessels. Gd-enhanced Magnetic Resonance Imaging (MRI) disclosed diffuse
      meningeal enhancement. RI cisternogram and CT-myelogram (CTM) suggested that the
      region of CSF leakage should be in the retrospinal area at the level of C1-2.
      Because orthostatic headache failed to resolve even with 3 weeks of bed rest,
      surgical intervention was successfully carried out to seal the site of CSF
      leakage with the use of a fascia and fibrin glue. We have speculated that the
      etiology of SAH might have been a secondary rupture of congestive intracranial
      veins, such as basilar plexus or bridging veins, induced by a decrease of
      intracranial CSF pressure.

PMID- 12187731
TI  - [A case of aneurysmal subarachnoid hemorrhage associated with bilateral common
      carotid artery occlusion].
AB  - Cerebral aneurysm may occur in some cases of major cerebral artery occlusion.
      However, according to our search of the literature, only four cases of aneurysmal
      subarchnoid hemorrhage (SAH) associated with bilateral common carotid artery
      occlusion (CCAO) have been reported in addition to the case we report here with a
      summary of the previously reported cases. A healthy 82-year-old female was found
      unconscious and admitted to our hospital where her neurological state was
      diagnosed as Hunt & Kosnik grade II, World Federation of Neurosurgical Societies
      grade II. General physical examination yielded no abnormal findings. A computed
      tomography (CT) scan of the head revealed a subarachnoid hemorrhage (Fisher's
      classification group 3). An aortogram demonstrated the presence of both vertebral
      arteries (VA), but the origins of the common carotid arteries (CCAS) were not
      visible at all. The left vertebral angiogram (VAG) revealed anastomosis between
      the muscle branch of the VA and the occipital artery, with retrograde blood flow
      through the external carotid artery supplying the internal carotid artery (ICA).
      These findings were also visible on the right VAG, but there was severe stenosis
      of the C2 portion of the right ICA. The right enlarged posterior communicating
      artery (Pcom) supplied the right ICA. Two saccular aneurysms arising from the
      junction of the right posterior cerebral artery (PCA) and the enlarged right Pcom
      and the P2 segment of right PCA, respectively were also observed. Aneurysm
      formation in this case was probably caused by hemodynamic stress secondary to
      bilateral CCAO induced by arteriosclerosis.

PMID- 12187732
TI  - [A case of internal carotid-posterior communicating artery aneurysm presenting
      pure acute subdural hematoma].
AB  - The incidence of acute subdural hematoma (SDH) due to a ruptured intracranial
      aneurysm varies from 0.5% to 7.9% of all intracranial aneurysms. Pure acute SDH
      without subarachnoid hemorrhage (SAH) is rare. According to the literature, only
      18 cases (including our case) of pure acute SDH identified by CT scan have been
      reported. Here we report a case of an internal carotid-posterior communicating
      artery (IC-PC) aneurysm presenting pure acute SDH identified by CT. We summarize
      the 18 reported cases. A 55-year-old female experienced severe headache on
      October 9, 1999, which did not improve after medication. Four days later, left
      ptosis began. She was admitted to the department of ophthalmology to treat
      oculomotor nerve paresis. A computed tomography (CT) scan obtained on admission,
      revealed no obvious abnormality. She was treated by hormonal therapy, but her
      symptoms continued. Ten days later, she suddenly lost consciousness and was
      transferred to our hospital. Although the CT scan revealed a thick left SDH with
      marked midline shift, SAH was absent. Her neurological state was Hunt & Kosnik
      grade IV. A left carotid angiogram revealed an IC-PC aneurysm with active
      extravasation. The patient was taken to the operating room for emergency removal
      of the SDH and aneurysmal neck clipping. During the operation, adhesion between
      the aneurysmal dome and the arachnoid was observed, but subarachnoid hemorrhage
      was not identified at all. The aneurysm was successfully clipped.
      Postoperatively, her consciousness improved immediately. In this case, the pure
      acute SDH identified by CT was responsible for causing the direct hemorrhage into
      the subdural space via an adhesive lesion.

PMID- 12187733
TI  - [Carotid endarterectomy in chronic renal failure patients: report of two cases].
AB  - Chronic renal failure is one of the risk factors for carotid atherosclerosis. We
      report two cases of stenosis of the carotid bifurcation treated by carotid
      endarterectomy. A 66-year-old man with a 17-year history of hemodialysis
      experienced repeated episodes of right hemiparesis. Cerebral angiography showed
      severe stenosis of the cervical carotid bifurcation bilaterally. Left and right
      carotid endarterectomy operations were performed one month apart. The
      postoperative course was uneventful, and the patient returned home without
      neurological symptoms. The second case was in a 49-year-old woman with a 15-year
      history of hemodialysis had vertigo of one month duration. Cerebral angiography
      revealed occlusion of the left subclavian artery, and the distal left axillary
      artery was filled by retrograde flow from the left vertebral artery. Stenosis of
      the right carotid bifurcation was also noted. Right carotid endarterectomy was
      performed without any complications. Although a high incidence of intraoperative
      complications and of recurrent stroke after carotid endarterectomy (CEA) has been
      reported in chronic renal failure patients, the poor prognosis of the natural
      history of severe carotid stenosis in chronic renal failure should be taken into
      consideration. The cases reported indicate that carotid endarterectomy is safe
      and justified for carotid stenosis in chronic renal failure patients.

PMID- 12187734
TI  - [Ruptured fenestrated aneurysm of vertebral artery union successfully treated by
      endovascular surgery with GDC].
AB  - It is difficult to operate on ruptured basilar artery aneurysms in the acute
      phase because of the anatomical complexity, brain swelling, patients' medical
      condition, etc., but because there is some risk of rebleeding and/or vasospasm if
      surgery is delayed, early surgery is recommended. We encountered a rare case of
      ruptured fenestrated aneurysm of the vertebral artery (VA) union, treated it
      safely by endovascular surgery with Guglielmi detachable coils (GDCs) in the
      acute phase, and obtained a good outcome after intensive care. We therefore
      conclude that endovascular surgery with GDCs is a first-line therapy for
      fenestrated aneurysms of the VA union in the acute phase after subarachnoid
      hemorrhage. Fenestrated aneurysms of the VA union are very rare, and long-term
      follow-up is mandatory.

PMID- 12187735
TI  - [A case of cerebral syphilitic gumma].
AB  - A 38-year-old man experienced an intermittent low-grade fever with generalized
      eruption, followed by rapidly progressive right hemiplegia. Neuroimaging revealed
      a ring-like enhanced mass in the left premotor cortex surrounded by marked
      perifocal edema. The syphilitic titer was high both in the serum and in the
      cerebrospinal fluid. Open biopsy of the lesion revealed the tumor consisted of
      inflammatory cells associated with plasmacyte infiltration to the perivascular
      region as well as to the dura, which is consistent with the definition of
      syphilitic gumma. The abnormalities in neurology and in neuroimaging improved
      dramatically after antisyphilitic treatment. Difficulties in differentiating a
      cerebral gumma from other diseases are discussed.

PMID- 12187736
TI  - [Head injury, no. 2 in series of articles: basic knowledge of neuropathology for
      neurosurgeons].

PMID- 12187737
TI  - [Problems and proposals from neurosurgical practice, no. 4 in series of articles:
      controversy and reform proposals concerning insured medical care in
      neurosurgery].

PMID- 12187738
TI  - [Results of urgent survey (April 11, 2002) by the Japan Neurosurgical Society,
      no. 5 in series of articles: controversy and reform proposals concerning insured
      medical care in neurosurgery].

PMID- 12187739
TI  - [Peptic ulcer in the elderly--general considerations, definition and
      classification].
AB  - People over age 60 constitute a substantial and growing proportion of the
      population in Japan. So it is important that caregivers need to keep in mind the
      approach to acid related disease in the elderly. We review the physiologic
      changes of the gastrointestinal tract and related organs with age, epidemiology,
      unique clinical features, and special considerations in management of digestive
      disorders in the elderly. Identifying physiologic changes that can be attributed
      to aging has proven to be quite difficult. Because normal changes of aging have
      produced conflicting results of changes due to diseases often found in elderly.
      In the elderly, the manifestation of peptic ulcer is more likely to be silent.
      The risk of complications, particularly when consuming NSAIDs, is increased in
      the elderly. Elderly individuals also poorly tolerate ulcer complications, in
      large part secondary to a higher risk of associated illness.

PMID- 12187740
TI  - [Epidemiology of peptic ulcer disease in the aged in Japan].
AB  - The population in Japan is now decreasing, however, the population older than 65
      years old is increasing remarkably in the recent years. The old people with
      peptic ulcer may hospitalize for longer period than that of younger. The serious
      complications such as bleeding, perforation and obstruction may affect the period
      of hospitalization. In 1983, Helicobacter pylori was found and identified. The
      eradication of Helicobacter pylori causes a decrease of ulcer recurrence and the
      lower prevalence rate of Helicobacter pylori in the younger people may decrease
      the incidence of peptic ulcer in the near feature. Thus, the people older than 65
      years old with a high risk for peptic ulcer will increase, although the infection
      rate of Helicobacter pylori will decrease. The actual number of peptic ulcer in
      the old people may decrease, however, the percentage of old people with peptic
      ulcer against total population may increase, although it is very difficult to
      predict the incidence of peptic ulcer diseases in the future.

PMID- 12187741
TI  - [Clinical features of peptic ulcer disease in the elderly].
AB  - Peptic ulcer disease in the elderly is considered to be more serious disorder
      than that in younger patients because of the presence of more risk factors and
      complications. Bleeding and perforation are the most frequent ulcer
      complications. Nonsteroidal anti-inflammatory drugs(NSAIDs)-induced ulcer is more
      prevalent, and atypical symptoms often lead to a delay in diagnosis and treatment
      in the elderly patients. These two factors may contribute to the greater
      mortality in the elderly. The treatment is directed toward gastric acid
      suppression in combination with elimination of causative factors such as H.
      pylori infection or NSAIDs, and the control for comorbid medical conditions. It
      is important to avoid unnecessary medications and clinicians should pay attention
      to drug interactions, especially some kinds of H2 receptor antagonists.

PMID- 12187742
TI  - [H. pylori infection in the aged].

PMID- 12187743
TI  - [Guidelines in the management of gastric ulcer with special reference to elderly
      patients].
AB  - Special care must be taken for peptic ulcer disease in the elderly because of
      more frequent complications such as major bleeding that require hospitalization
      and may sometimes result in fatal outcome. In addition, elderly patients are more
      vulnerable to such complications due to accompanying systemic diseases such as
      cardiovascular, pulmonary or liver diseases. Therefore, it is important to
      prevent ulcer complications for the high-risk group in the elderly. For the
      prevention and treatment of ulcer disease in elderly patients, medication with
      fewer drug-interactions given in simple dose schedule is preferable for better
      compliance as well as for reducing side effects. Furthermore, consideration on
      cost-effectiveness of the treatment is increasingly important because of severe
      burden on the health insurance system. In an attempt to give better and more
      efficient management strategy for gastric ulcer, evidence-based clinical
      guideline is being prepared under the support of Japanese Ministry of Health and
      Welfare. Rational management of ulcer disease in the elderly, however, requires
      deliberate consideration of each patient status and stringent, inflexible
      application of the guideline should be avoided.

PMID- 12187745
TI  - [Pathophysiology of reflux esophagitis in the elderly patients].
AB  - Recent reports indicate an increased prevalence of reflux esophagitis(RE) in
      Japan. There are many factors causing RE, and many kinds of changes associating
      aging are important in the causes of RE in the elderly patients. Characteristic
      features of the causes of RE in elderly patients are summarized here. Within the
      elderly patients, there are cases with persistent gastric acid secretion. Aging
      affections lead to esophageal motor dysfunctions and to failure of LES
      function(presbyesophagus). The elderly are complicated by orthopedic degenerative
      diseases with posture change due to osteoporosis; some pharmaceutical agents such
      as Ca-channel blockers or NSAIDs. Hiatal hernia is also an aggravating factor. In
      the future, elderly people with persistent gastric acid secretion will be
      increased based on declining prevalence of Helicobacter pylori. Therefore further
      increase in the prevalence and development of RE is foreseen in our country.
      Pathophysiology of RE in the elderly patients is expected to show various changes
      in the future.

PMID- 12187746
TI  - [NSAIDs induced gastroduodenal ulcer in the aged].
AB  - The main drugs causing gastroduodenal ulcers are NSAIDs, steroids, antibiotics
      and anticancer agents. Among these causative drugs, nonsteroidal antiinflammatory
      drugs (NSAIDs) ranked first, followed by steroids, antibiotics, anticancer agents
      and other drugs, including over the counter drugs for the management of pain and
      common cold. Mechanisms of mucosal injury of NSAIDs are mainly direct inhibition
      cyclooxygenase (COX), mucosal injury by free radicals and direct contact of a
      drug to mucosa according to high acidity and high osmotic pressure. Clinical
      features of NSAIDs induced gastric ulcers are below: ulcer location concentrated
      in the pyloric region to the antrum, comprising three-fourths of all cases,
      multiple ulcers are found in 24% of the subjects. The frequency of relatively
      small ulcers, surrounded by highly swollen mucosa, is high. Deeply dug ulcers and
      large, irregularly shaped ulcers are also characteristic findings. NSAIDs induced
      bleeding gastroduodenal ulcers are seen in 21% of bleeding gastric ulcers which
      are stopped by the hemostatic method using pure ethanol injection. More than 80%
      of the cases are in the aged. All cases are successfully stopped bleeding and
      treated conservatively.

PMID- 12187744
TI  - [Pathogenesis of gastric and duodenal ulcer in the elderly].
AB  - In the elderly, H. pylori infection and nonsteroidal anti-inflammatory
      drug(NSAID) use are most important risk factors for peptic ulcer disease. It is
      now recognized that, in patients with H. pylori infection, nonatrophic antral
      predominant gastritis results in increased acid secretion, which is seen in
      duodenal ulcer patients, whereas corpus-predominant gastritis and pangastritis
      result in decreased acid secretion, that are seen in patients with proximal
      gastric ulcer and gastric cancer. These physiological changes are considered to
      be related to disease outcome. On the other hand, NSAIDs induced gastrointestinal
      toxicity is primarily due to the inhibition of mucosal prostaglandin synthesis in
      the gastric mucosa, which subsequently impairs the gastric cytoprotective
      factors. These two factors may independently, or even synergistically, cause the
      development of peptic ulcer disease in the elderly.

PMID- 12187747
TI  - [Some problems during esophagogastroduonenoscopy for elderly patients].
AB  - Esophagogastroduonenoscopy(EGD) is a useful tool not only for diagnostic
      examination but also for less invasive treatment. However, it is the well-known
      fact that complications occur during EGD, particularly in elderly patients. We
      reviewed EGD performed for elderly patients. Arrhythmia, elevated blood pressure
      over 50 mmHg, increased the pulse rates and decreased of oxygen saturation during
      EGD were more common in elderly patients. Changes in these parameters occurred
      more frequently when EGD passed through the pharynx at the time of insertion. In
      conclusion, EGD for elderly patients should be performed more gently and
      carefully, particularly at the time of insertion.

PMID- 12187748
TI  - [Radiological examination for elderly patients with peptic ulcer].
AB  - In this review, radiological examination for elderly patients was discussed. In
      recent years, technology for endoscopy was remarkably developed and endoscopical
      diagnosis of peptic ulcer became much easier and safer than before. Thus,
      indication of a biphasic radiologic examination is decreasing especially for the
      elderly patients. There are many problems for radiological examination in the
      elderly. Most of problems are based on aging, i.e. difficulties in swallowing,
      moving, defecation, understanding instruction, etc. Clinical characteristics of
      peptic ulcer in aging people should be considered. The knowledge of complaining,
      complications, ulcer location, and etiology including H. pylori infection might
      be also important. These issues should be well understood before performing
      radiological examination in the elderly.

PMID- 12187749
TI  - [Diagnosis of Helicobacter pylori infection].
AB  - Peptic ulcer in elderly patients may be associated with Helicobacter pylori
      infection. Diagnosis for H. pylori infection should be needed in these patients.
      The test may be resulted in false negative in case of invasive diagnostic methods
      based gastric biopsy, because atrophic gastritis and intestinal metaplasia
      developed in patients may not be able to detect scarce infection of the
      bacterium. Urea breath test or stool antigen test are recommended for diagnosis
      of H. pylori infection in patients. It is suitable for patients, because of the
      non invasive nature of these diagnostic tests.

PMID- 12187750
TI  - [Prevention and treatment of gastro-duodenal ulcers in elderly--from theory-based
      toward evidence-based].
AB  - Aging is one of the major risk factors for development of gastroduodenal ulcers,
      probably reflecting increased incidence of H. pylori infection and age-dependent
      decreases in mucosal blood flow, prostaglandin synthesis, etc. Increased risks
      for other systemic disorders such as cardiovascular attacks and increased use of
      drugs such as NSAIDs also play important roles in ulcer susceptibility in the
      elderly. Recent clinical evidences clearly show that certain anti-ulcer
      agents(misoprostol, proton pump inhibitors and an H2-receptor antagonist in a
      high-dose) are effective in prevention and treatment of NSAIDs-ulcers.
      Interestingly, efficiency of these anti-ulcer drugs significantly changes
      depending on age and history of NSAIDs ulcers and cardiovascular disorders. For
      an example, prevention with misoprostol is significantly efficient in the elderly
      with ulcer history. Thus, ulcer prevention and treatment should be planned in a
      tailor-made manner in future clinical practice in the elderly.

PMID- 12187752
TI  - [Eradication therapy of Helicobacter pylori for elderly patients in Japan].
AB  - In Japan, an eradication therapy of Helicobacter pylori(H. pylori) for peptic
      ulcers of stomach and duodenum was approved by a health insurance since November
      1, 2000. A method of an eradication therapy is as follows. Adult patients are
      received lansoprazole 30 mg, amoxicillin 750 mg, clarithromycin 200-400 mg at the
      same time twice daily for seven days. This therapy is based on a guideline of a
      Japanese association of Helicobacter Research. Many elderly patients have
      complications such as hypertension, cerebral vascular disturbance, heart failure
      and so on. Moreover, they often take a several medicine including NSAIDs(non
      steroidal anti-inflammatory drugs). Therefore, you should pay attention
      especially to interaction of drugs when planning an eradication therapy of H.
      pylori for elderly patients.

PMID- 12187751
TI  - [Reflux esophagitis].
AB  - There are some factors which influence reflux esophagitis, in our country
      atrophic gastritis is important for the degree of it especially. Helicobacter
      pylori(H.P.) infection is popular in aged patients, so atrophic gastritis is also
      popular in such patients, then the frequency of reflux esophagitis is low
      comparing with other countries. But because of the late of H.P. infection comes
      to be higher and the eradication therapy for the peptic ulcer diseases has been
      done in these days, the late of atrophic gastritis comes to be lower and reflux
      esophagitis comes to be higher. In aged patients medication and physical factors
      influence reflux esophagitis and these factors are different in each patient. So
      it is very important to treat the patient of reflux esophagitis considering of
      each factor.

PMID- 12187753
TI  - [Management of gastrointestinal mucosal damage in patients with cerebrovascular
      disease].
AB  - Cerebro-vascular disorders are often accompanied by gastrointestinal mucosal
      damages which possibly result in life-threatening massive hemorrhage. Such
      gastrointestinal complications in acute phase of stroke are usually regarded as
      one of stress-induced lesions. The pathophysiologic investigation of stress
      related gastroduodenal mucosal damages has suggested that increased activity of
      the autonomic nervous system, in particular sympathetic nervous system, plays an
      important role in the development of gastric mucosal lesions. The suppression of
      gastric acid secretion by using H2-receptor antagonists or proton-pump inhibitors
      is useful for the prevention and management of stroke-induced gastric mucosal
      damages. In the chronic phase, the drug-induced gastrointestinal mucosal lesions
      may increase because steroids, non-steroidal anti-inflammatory drugs,
      anticoagulant and antiplatelet drugs are frequently applied to patients with
      stroke. The endoscopic interventions such as clipping, infusion of ethanol or
      epinephrine-contained hyperosmotic saline, and coagulation are effective against
      gastroduodenal hemorrhage.

PMID- 12187754
TI  - [Peptic ulcer in patients with diabetes mellitus].
AB  - It is well recognized that diabetes mellitus develop a variety of complications
      during the course of disease, such as diabetic triopathy. After one to two
      decades of overt disease, approximately 30-60% of diabetics develop clinical
      signs of visceral autonomic neuropathy. Peptic ulcer patients with diabetes
      mellitus have these complicated backgrounds. The prevalence of peptic ulcer
      disease in asymptomatic diabetic patients was reported as 5.3% to 7.3% in Japan.
      We evaluated the efficacy of Helicobacter pylori eradication therapy in peptic
      ulcer patients with non-insulin dependent diabetes mellitus. The cure rate of
      peptic ulcer and gastritis score at 8 weeks after eradication therapy is similar
      with non-diabetic patients. Our data suggests that the eradication of
      Helicobacter pylori becomes a first therapy in peptic ulcer patients with non
      insulin dependent diabetes mellitus.

PMID- 12187755
TI  - [Treatment of peptic ulcer related to rheumatic diseases].
AB  - Rheumatic diseases often have gastrointestinal(GI) manifestations, and may
      present as GI bleeding and perforation due to peptic ulcer associated with high
      mortality. Major causes of peptic ulcer related to rheumatic diseases are drugs
      such as nonsteroidal anti-inflammatory drug(NSAID) and corticosteroid, and
      vasculitis. The analgesic effects of NSAID often mask abdominal pain until they
      cause GI bleeding and perforation. Therefore, it is important to make early
      diagnosis of peptic ulcer with upper gastrointestinal endoscope. Fundamental
      treatment of NSAID induced peptic ulcer is to quit it, however it is difficult
      because of activity of rheumatic diseases. Also, most NSAID induced peptic ulcers
      heal by administration of proton pump inhibitor or misoprostol. Corticosteroid
      pulse therapy or administration of immunosuppressant agents is effective for
      vasculitis induced peptic ulcer, however it is difficult to make diagnosis of it.
      Development of NSAID with less side effects such as cyclooxygenase-2 selective
      inhibitors and establishment of diagnosis and treatment of peptic ulcer related
      to rheumatic diseases are expected.

PMID- 12187756
TI  - [Liver cirrhosis].
AB  - The prevalence of the peptic ulcer in the aged associated with liver cirrhosis is
      not so high in comparison with that of the younger. But if bleeding occurs, it is
      very difficult to stop it and it influences the prognosis of the patients. The
      factors of liver cirrhosis which influence the therapy of peptic ulcer are
      bleeding tendency, hypoalbuminemia, hepatic encephalopathy, and hepatorenal
      syndrome. The therapies on the peptic ulcer of the aged associated with liver
      cirrhosis are consisted with rest therapy, diet therapy, and drug therapy. It is
      necessary to consider the level of liver function to decide the therapies. If
      bleeding occurs, the endoscopic therapy is effective, and if the patient fall to
      the shock status, it is necessary to consider the operation as soon as possible.
      It is important to evaluate the liver function to select the therapies.

PMID- 12187757
TI  - [Chronic respiratory disease and gastroesophageal reflux].
AB  - Both GERD(gastroesophageal reflux disease) and chronic respiratory disease are
      common disease in old and the association between GERD and chronic respiratory
      disease are recently proved in many reports. Patient with GERD have a higher
      prevalence of asthma and chronic cough. Aggressive antireflux therapy in patient
      with asthma and GERD results in improvement in asthma outcome. In our study,
      endoscopic examination revealed that the prevalence of esophageal mucosal disease
      in patient with asthma was about 83%. In this paper, I review the role of GERD in
      chronic respiratory disease, especially asthma.

PMID- 12187758
TI  - [The treatment of peptic ulcer in elderly CRF patients].
AB  - It is well known that CRF patients may suffer from various types of upper GI
      tract lesions such as esophagitis, erosive or atrophic gastritis, gastro-duodenal
      ulcers and polyps. Above all, acute gastric mucosal lesion with atrophic changes
      has been complicated with elderly CRF patients in relatively high frequency in
      recent years. A number of causes for upper GI tract lesions in CRF patients have
      been raised, which include mental and physical stresses, hypergastrinemia
      associated with lower renal metabolic clearance rate, secondary
      hyperparathyroidism, hypoperfusion in gastric mucosal blood flow, malnutrition,
      and also H. pylori recently. The treatments for these upper GI tract lesions are
      directed toward both suppression of offensive factors and strengthening of
      defensive factors in gastro-duodenal mucosae. It is needless to say that special
      attentions should be always paid for doses, intervals or durations in any drugs
      prescribed for elderly CRF patients because of lower renal metabolic clearance
      rates for drugs.

PMID- 12187759
TI  - [Several points that should be noticed during PPI treatment for peptic ulcers in
      elderly patients].
AB  - Proton pump inhibitor(PPI) is used for the treatment of peptic ulcer diseases for
      the following three purposes. Firstly, it is used to facilitate the ulcer healing
      and pain relief. Secondly, it is used for the eradication of H. pylori to
      minimize the recurrence of ulcer diseases. Thirdly, intravenous infusion of PPI
      is used for the hemostasis in patients with bleeding ulcers. Plasma concentration
      and acid suppressing effect of PPI are reported to be slightly augmented when
      standard doses of PPI are used in elderly cases. Since PPI is a safe drug and age
      related increase in its plasma concentration is not remarkable, the dose
      adjustment of PPI may not be necessary even in elderly patients. Some PPIs are,
      however, reported to have metabolic interactions with other drugs such as
      diazepam and digoxin. Therefore drug interaction should be considered when the
      PPI is administered to the elderly with accompanying diseases.

PMID- 12187760
TI  - [What is important in treating elderly with H2 receptor antagonists].
AB  - Histamine 2 receptor antagonists (H2RA) has widely been used for the treatment of
      peptic ulcer or reflux esophagitis. H2RAs are relatively safe drugs and recently
      in Japan they can be purchased by over the counter without a doctor's
      prescription. However, in elderly, drug metabolism is different from younger
      people, so that there are several important points in treating elderly. First of
      all, elder people tend to have poor renal function. Dosage of H2RAs should be
      lowered accordingly. In particular, cimetidine is known to interfere with other
      drugs through hepatic metabolism, the concentration of co-committant drugs such
      as warfarin, benzodiazepine tend to be elevated. Cimetidine should be replaced by
      the other H2RAs which have no such effects.

PMID- 12187761
TI  - [Prostaglandin derivatives--indication and critical points].
AB  - After discovery of H. pylori, management of peptic ulcer disease (PUD) is getting
      much easier. However, four thousands a year still died caused by this disease in
      Japan. Ten to twenty percent of the non-NSAIDs ulcer could be expected to remain
      after complete eradication of H. pylori; The number could be still 100,000
      200,000 a year in Japan. Furthermore, NSAIDs ulcer would not decrease in number
      in the post-H. pylori era. Recurrence of ulcer is related to the quality of ulcer
      healing. Deficiency of prostaglandins(PG) in the mucosa is another main reason
      than H. pylori infection of poor quality of ulcer healing. Therefore, a PG
      analogue may be a most reasonable tool for treatment of H. pylori-negative PUD
      including NSAIDs ulcer, but is often poorly tolerated because of diarrhea and
      abdominal pain. The mucosal damage caused by NSAIDs is also gastric acid
      dependent and so, an H2-receptor antagonist is to some extent effective although
      the efficacy is far behind of that with a PG-analogue. Recently, a proton-pump
      inhibitor has been reported to exert the same effect as a PG-analogue in healing
      of gastroduodenal mucosal damage caused by NSAIDs and the superior effect in
      preventing recurrence of the damage with better tolerance. This results suggest
      that strong acid inhibition is highly effective for such damage. Whether such
      strong acid inhibition causes disturbance of absorption of NSAIDs is not clear,
      which might result in poor antiinflammatory effect. Elderly patients often have
      tendency of constipation and less possibility of pregnancy. Therefore, a PG
      analogue may be not only safe but also more favorable for such patients.

PMID- 12187762
TI  - [Medication adherence in elderly patients].

PMID- 12187763
TI  - [QOL and the older people with peptic ulcer].
AB  - The population older than 65 years old in Japan is now increasing in the recent
      years. The peptic ulcer, especially complicated peptic ulcers such as bleeding
      ulcer or perforating ulcer may disturb the quality of life in the older people
      because of long term hospitalization or death. To evaluate the characteristics of
      gastric mucosa in the older people, we investigated the mucosal blood volume
      using reflectance spectrophotometry and measured adenine nucleotides in biopsy
      samples from gastric mucosa using high-performance liquid chromatography. In the
      elderly, the mucosal blood volume significantly decreased according to aging and
      energy metabolism in human gastric mucosa was impaired. This may weaken their
      defensive mechanism. The combination therapy cimetidine and ecabet sodium
      compared with cimetidine alone showed a significant higher ulcer healing rate and
      symptom relief rate. Thus, the combination therapy with mucoprotective agents and
      acid suppressant accelerates ulcer healing and symptom relief and may maintain
      QOL in the old people with peptic ulcers. However, in the recent studies,
      Helicobacter pylori infection may affect these factors in the elderly. Therefore,
      we should reinvestigate the changes of mucosal defensive factors by aging.

PMID- 12187764
TI  - [Occurrence of upper gastrointestinal tract disease after Helicobacter pylori
      eradication].
AB  - Helicobacter pylori infection is recognized to be a pathogen of various
      gastroduodenal disease. Eradication therapy of H. pylori reduces the recurrence
      of gastro-duodenal ulcer, improves histological gastritis, and is suggested to
      act a certain role in protection against gastric carcinogenesis. Although,
      several studies show uncomfortable results arise after H. pylori infection was
      cured. These studies suggest that gastro-esophageal reflux disease (GERD) and
      gastro-duodenal erosion may increase after successful eradication of H. pylori.
      Recently, adenocarcinoma of the gastric cardia and esophagus increase in
      incidence. Reflux esophagitis and Barrett's esophagus are recognized as
      precancerous lesion of esophageal adenocarcinoma. It is uncertain the association
      of newly occurrence of GERD after H. pylori eradication and increase of
      esophageal adenocarcinoma. GERD may cause adenocarcinoma development, though long
      term observations is necessary after H. pylori eradication.

PMID- 12187765
TI  - [Smoking, alcohol and peptic ulcer in the elderly].
AB  - The associations between smoking, alcohol intake and peptic ulcer have been
      investigated not a few. And it is obvious that smoking aggravate peptic ulcers.
      With increasing age the percentage of smoker decrease, however, 49.2 percent of
      men at ages over 70 still smoke in Japan. Giving up smoking is important in the
      prevention of peptic ulcers. On the other hand, it is not regarded that peptic
      ulcers are correlated with alcohol intake. But alcohol intake causes the acute
      injury of the gastric mucosa. It seems that moderate drinking is important in the
      prevention of peptic ulcers, especially in the elderly.

PMID- 12187766
TI  - [Prospects of the therapeutic approaches to Creutzfeldt-Jakob disease: a clinical
      trial of antimalarial, quinacrine].
AB  - Prion diseases are lethal transmissible neurodegenerative illnesses that affect
      humans and many other animals. Since the accumulation of the pathogenic form of
      prion protein is a pivotal event in prion diseases, most of the therapeutic
      strategies are designed to prevent the conformational change of normal prion
      protein to that of the pathogenic form or to remove the accumulated prion
      protein. Quinacrine is one of the compounds that can inhibit the accumulation of
      pathogenic prion protein in cultured neuroblastoma cells. Here we report the
      results of clinical trials of quinacrine administration to the patients of
      Creutzfeldt-Jakob disease. In some patients, response to visual and auditory
      stimulations improved transiently. Lemon-yellow discolorization of skin and liver
      dysfunction were common side effects by quinacrine.

PMID- 12187767
TI  - [Fundamental and applied studies on transport and metabolism of electrolytes and
      glucose--aim to contact with molecular biology].
AB  - The authors' research focuses on polyuria, natriuresis, glucosuria, glycemia, and
      renal calcification in occupational lead poisoning and endemic fluorosis. Changes
      in electrolyte mobilization and in glucose metabolism and transport following the
      administration of lead compounds or fluoride were examined to elucidate these
      mechanisms. The results suggest fundamental approaches to the mechanism of aging
      and life style diseases. Our results show that: 1) Natriuresis and polyuria in
      lead poisoning and fluorosis are due to a decrease in renal Na/K-ATPase activity;
      2) Renal calcification in fluorosis is due to stimulation of parathyroid function
      and activation of the renal phosphatidylinositol cascade; 3) Glycemia in
      fluorosis is due to elevation of renal and hepatic glucose-6-phosphatase
      activities; 4) Glusosuria in fluorosis is due to decreased renal Na/K-ATPase
      activity (but fluoride administered directly did not damage the renal Na/glucose
      cotransporter (SGLT); 5) Renal calcification in fluorosis is due to stimulation
      of parathyroid function; and 6) The decrease in renal Na/K-ATPase and SGLT
      activities with aging and hypertension is due to a decrease in phosphorylation
      activity by protein kinase C (PKC) etc. (decrease in PKC productivity with aging
      and hypertension).

PMID- 12187768
TI  - [Molecular toxicological mechanism of the lethal interactions of the new
      antiviral drug, sorivudine, with 5-fluorouracil prodrugs and genetic deficiency
      of dihydropyrimidine dehydrogenase].
AB  - In 1993, there were 18 acute deaths in Japanese patients who had the viral
      disease herpes zoster and were treated with the new antiviral drug sorivudine
      (SRV, 1-beta-D-arabinofuranosyl-(E)-5-(2-bromovinyl)uracil). All the dead
      patients had received a 5-fluorouracil (5-FU) prodrug as anticancer chemotherapy
      concomitant with SRV administration. Studies on toxicokinetics in rats and on
      hepatic dihydropyrimidine dehydrogenase (DPD), a rate-limiting enzyme for 5-FU
      catabolism in rats and humans, strongly suggested that in the patients who
      received both SRV and the 5-FU prodrug, tissue levels of highly toxic 5-FU
      markedly increased as a result of irreversible inactivation of DPD in the
      presence of NADPH by 5-(2-bromovinyl)uracil (BVU), a metabolite formed from SRV
      by gut flora in rats and humans. Recombinant human (h) DPD was also irreversibly
      inactivated by [14C] BVU in the presence of NADPH. MALDI-TOF MS analysis of
      radioactive tryptic fragments from the radiolabeled and inactivated hDPD
      demonstrated that a Cys residue located at position 671 in the pyrimidine-binding
      domain of hDPD was modified with an allyl bromide type of reactive metabolite,
      dihydro-BVU. Thus artificial DPD deficiency caused by BVU from SRV led to patient
      deaths when coadministered with the 5-FU prodrug. Human population studies using
      healthy volunteers have demonstrated that there are poor and extensive 5-FU
      metabolizers who have very low and high DPD activities, respectively.
      Administration of a clinical dose of 5-FU or its prodrug to poor 5-FU
      metabolizers may cause death unless DPD activity is determined using their
      peripheral blood mononuclear cells prior to the administration of the anticancer
      drug.

PMID- 12187769
TI  - [Foundation of the bases for protein research and its application to the
      pharmaceutical science field].
AB  - This paper reviews the results of basic research conducted by the author's group
      to determine appropriate methods to develop protein-based drugs. These include
      production strategies, elucidation of physiologic function, improving existing
      pharmaceuticals, de novo design, and protein reconstruction. The antigenicity of
      modified proteins and methods to induce antigenic protein tolerance are also
      described.

PMID- 12187770
TI  - [Induction of cell differentiation and development of new anticancer drugs].
AB  - Cell differentiation is essential for normal growth and homeostasis, and drug
      induced differentiation of tumor cells into benign or normal cells is an
      important approach for anticancer chemotherapy. Studies of induction mechanisms
      for cell differentiation and discovery of differentiation-inducing factors are
      thus critical components of drug development. The Screening of differentiation
      inducing factors, such as purified aldehyde reductase, a xenobiotic metabolite
      enzyme, that induces differentiation of human acute myeloid leukemia HL60 cells
      into monocyte/macrophage cells is described. Mechanisms of all-trans-retinoic
      acid (RA)-induced differentiation are also covered. RA is a potent inducer of
      HL60 cell differentiation and when used as a sole agent it can induce complete
      remission in patients with acute promyelocytic leukemia (APL). While one
      mechanism of the effect of RA involves RA nuclear receptors, retinoylation (a
      posttranslational modification of proteins by RA) may be a new nongenomic
      mechanism by which RA acts on cells. An early event in RA-induced differentiation
      may be retinoylation of RII alpha (regulatory subunits of cAMP-dependent protein
      kinase), in which RII alpha units are retinoylated and the retinoylated RII alpha
      is then translocated to the nucleus. Drugs can also be combined with RA in RA
      differentiation therapy. Cytodifferation therapy by RA in APL patients exhibits
      limitations due to the resistance of relapsed patients to further RA treatment.
      This may occur through the induction of expression of various genes that reduce
      RA blood concentrations. Treatment with combinations of RA and other agents may
      be one way to reduce induction of those genes. Good candidates for such agents
      include cAMP-elevating agents, retinoids, steroids, and fatty acids that
      synergistically induce differentiation of HL60 cells. Two derivatives of
      falconensone A, falconensone A p-bromophenylhydrazone, which has a bromophenyl
      residue, and falconensone A dioxime, which possesses a hydroxy residue, were
      synthesized to incorporate features of RA and N-[4-hydroxyphenyl] retinamide.
      Both derivatives have exhibited more potent biological activity than the parent
      falconensone A in vitro and in vivo.

PMID- 12187771
TI  - [Binding of G alpha o N-terminus is responsible for the voltage-resistant
      inhibition of alpha 1A (P/Q-type, Cav2.1) Ca2+ channels].
AB  - G-protein-mediated inhibition of presynaptic voltage-dependent Ca2+ channels is
      comprised of voltage-dependent and--resistant components. The former is caused by
      a direct interaction of Ca2+ channel alpha 1 subunits with G beta gamma, whereas
      the latter has not been well characterized. Here, we show that the N-terminus of
      G alpha o is critical for the interaction with the C-terminus of the P/Q-type
      channel subunit, and that the binding induces voltage-resistant inhibition. A P/Q
      type C-terminal peptide, an antiserum raised against the G alpha o N-terminus,
      and a G alpha o N-terminal peptide all attenuated the voltage-resistant
      inhibition of P/Q-type currents. Furthermore, the N-terminus of G alpha o bound
      to the C-terminus of alpha 1A in vitro, which was prevented either by the P/Q
      type channel C-terminal or G alpha o N-terminal peptide. Although the C-terminal
      domain of the N-type channel showed similar ability to binding with G alpha o N
      terminus, the above-mentioned treatments were ineffective in the N-type channel
      current. These findings demonstrate that the voltage-resistant inhibition of the
      P/Q-type channel is caused by the interaction between the C-terminal domain of
      the Ca2+ channel alpha 1A subunit and the N-terminal region of G alpha o.

PMID- 12187772
TI  - [Creation and evaluation of the respective rank problem solution worksheet for
      improvement pharmaceutical management quality].
AB  - A respective rank problem solution worksheet was developed focusing on problem
      solution in training in pharmaceutical management. How the training influenced
      the instructions given to patients was then evaluated in two pharmacists in the
      NTT East Kanto Medical Center and three in an Ofuna central hospital. After the
      five pharmacists underwent the training, the records of 10 medication
      instructions to patients given by each before and after the training were
      compared. The records were analyzed based on a point calculation table, and the
      number of acquisition points was computed. The acquisition points increased
      significantly after training for all five pharmacists, from a mean of 3.56 before
      training to a mean of 8.34 after training. Although the acquisition points
      related to patient education were high, those for intervention during therapeutic
      monitoring, such as for adverse drug reaction or the selection of appropriate
      pharmaceuticals were acceptable, increasing to a mean 8.4 items after training
      compared with 4.4 items before. The respective rank problem solution worksheet is
      therefore considered useful in improving the quality of training pharmaceutical
      management.

PMID- 12187773
TI  - [Investigation and multivariate statistical analysis of the factors influencing
      risk management].
AB  - A questionnaire survey for medical practitioners was conducted to clarify their
      basic awareness and concepts of risk management. One hundred and sixty-three
      medical practitioners participated in the fourth. Chugoku Yakugaku Kenkyukai.
      More than 50% of the participants (n = 83, aged 39.7 +/- 10.8 years) answered
      correctly questions about the awareness of risk management and the existence of a
      risk management committee in their medical institution. All of those survey
      participants had experienced common risk managements incidents (approximately 12
      times/year) during working hours. When multivariate statistical analysis was
      performed on the survey results, the factors influencing the presence of a risk
      management committee in a medical institution were a system for the submission of
      incident reports, the number of beds, and the presence of a person assigned to
      manage risk. The analysis showed that in a number of cases medical institutions
      did not have a system for incident reports and did not appoint risk management
      staff. Moreover, the analysis showed that factors influencing the presence of a
      risk management committee were staff age, experience in submitting incident
      reports, and participation of the top executive in the operation of the risk
      management committee. Participants younger than 40 years of age were dissatisfied
      with the reporting system of risk management committees those older. The younger
      group usually reported incidents to those older than 40 years of age, who only
      accepted the reports and did not submit them to the risk management committee. In
      conclusion, our results suggest that in a risk management program it is important
      to establish a committee and a system for the submission of incident reports.
      Incident reports should not only include expressions of regret for medication
      errors but also propose a plan for improvement.

PMID- 12187774
TI  - [Appropriate administration schedule of D-penicillamine for pediatric Wilson's
      disease patients based on urinary copper excretion].
AB  - The purpose of this study was to increase the amount of copper excreted resulting
      from the administration of D-penicillamine(DP) in pediatric Wilson's disease(WD)
      patients. By measuring the urinary copper excretion after adjusting the
      administration schedules, the appropriate timing for DP administration was
      investigated. The subjects were three brothers with pediatric WD. The initial
      daily dose of DP was 5 mg/kg/day, and gradually increased to the maintenance dose
      of 20 mg/kg/day. Until the maintenance daily dose was reached, DP was
      administered 2 h after the morning and evening meal. After reaching the
      maintenance daily dose of DP, the appropriate timing for taking DP was
      investigated in both the morning and evening. Three schedules of DP
      administration were compared: 2 h after meals; 30 min before meals (with
      fasting); and 1 h before the morning and 1.5 before the evening meal (direction
      1). The resulting urinary copper excretion on each dosing schedule was compared.
      Little difference was found in urinary copper excretion on the first two
      schedules, i.e., 2 h after meals and 30 min before meals. When DP was
      administered 30 min before meals, urinary copper excretion [microgram/day] was
      1173 in the first brother, 918 in the second, and 875 in the third. When DP was
      administered according to direction 1, however, urinary copper excretion was
      increased significantly to 1701 in the first brother, 2701 in the second, and
      3808 in the third. It is known that the efficiency of urinary copper excretion
      with DP administration depends on the maintenance of chelating ability after
      absorption from the gastrointestinal tract. Our results indicate that the
      excretion was lower when DP was administered 2 h after or 30 min before meals
      (with fasting), as recommended in the package insert. Thus to achieve better
      copper excretion efficiency, direction 1 is recommended for WD patients.

PMID- 12187775
TI  - [Evaluation of the permeability of corticosteroid in hairless mouse and hairless
      micropig skin from admixture of commercially available corticosteroid ointments
      and/or creams].
AB  - Yucatan hairless micropig (YHMP) skin has been shown to have histology and
      physiologic properties similar to human skin. To assess the relationship between
      the permeability of corticosteroid ointments and five types of commonly used
      admixtures of corticosteroid through hairless mice (HM) or YHMP skin and the
      clinical effects in humans, we conduct by in vitro experiments using HM and YHMP
      skin. The permeability of corticosteroid in admixtures with urea or heparinoid
      ointments across HM or YHMP skin was 1.5-4-fold greater than that of
      corticosteroid ointments alone. HM skin was found to have faster permeability
      than YHMP skin, but otherwise was similar to YHMP skin. These experiments
      demonstrated a close relationship between the permeability of HM or YHMP skin and
      vasoconstrictor activity in humans. These results suggest that the in vitro
      permeability of corticosteroid measurements across HM skin could be a useful,
      rapid, and easy method for assessing the vasoconstrictor activity of topical
      corticosteroids and the admixtures of commercially available ointments and/or
      creams in humans.

PMID- 12187776
TI  - [A trial production of a table of the optical crystallographic characteristics of
      crystalline drugs including crystal habits (study of crystalline drugs by means
      of a polarizing microscope. XIX].
AB  - It was clarified in previous report that the predominant faces of crystal habits
      mainly coincide with the morphologic crystal face at (001), (010), or (100), and
      therefore the two measurable key refractive indices are closely related to the
      principal sections of the two axial wave surfaces and coincide with the one or
      two of the three principal refractive indices. The three principal refractive
      indices of biaxial crystalline drugs were measured and tabulated in the "General
      Information" section of the National Formulary compiled by the American
      Pharmaceutical Association. A series of studies was conducted to measure the key
      refractive indices of the crystalline drugs listed in the Japanese Pharmacopoeia
      X or XI so that the data could be used to improve the quantitative analysis of
      their crystal habits. The purpose of the present study was to examine data on
      both the key and principal refractive indices and attempt to produce a general
      authorized table of optic crystallographic characteristics, including crystal
      habits, for simpler and more reliable polarizing microscopy studies.

PMID- 12187777
TI  - Physical properties of the cerebral hemispheres and paw preferences in mongrel
      cats: sex-related differences.
AB  - This study was performed on 30 female and 18 male mongrel cats, of which 36
      appeared to be right- and 12 left-pawed, respectively. The physical features of
      the brain hemispheres and the paw preferences in cats were investigated related
      to both functional and morphological asymmetry. Right-pawed cats were more
      prevalent, with scores ranging from +60 to +80%, as compared with the left-pawed
      ones scoring from -40 to -60%. However, females were found to be more right-pawed
      than males, but the differences were not considered significant (p > .05). After
      half-open ether anesthesia, the whole brain was excised by craniotomy under deep
      anesthesia (Ketalar: 40-50 mg/kg). The brains excised were kept in formaldehyde
      (10%) for three days, and then the weight, volume, density, and the morphological
      dimensions of left and right hemispheres and whole brain bodies were measured.
      There were no significant sex-related differences in body weights and paw
      preferences; nor was there any relation among the weights, volumes, and lengths
      of right and left hemispheres in either sex. There was, however, a significant
      sex-related difference between the mean heights of the left hemispheres of both
      male and female cats (p < .05), which is expected to be on the right hemispheres.
      As for the total samples, the mean density of the left hemispheres exceeded that
      of the right hemispheres.

PMID- 12187778
TI  - Role of nitric oxide on age-dependent alterations: investigation of
      electrophysiologic and biochemical parameters.

PMID- 12187779
TI  - The cell assembly, Mark III: transitions between brain states and the
      localization and generalization of function.
AB  - A connectionist model of the cerebral cortex as a Markov chain is presented. The
      model reconciles localization of cortical functions, apparent in
      neuropsychological data, with the equipotentiality and diffusion of function that
      was noted in classical studies of learning. In addition, the model suggests that
      the specificity of some cortical activity can develop quickly from initial
      connections that are predominantly chaotic. It is not necessary to assume a high
      degree of "prewired" connections in the cortex of newborns. While the model does
      not require initial settings to be chaotic, neither does it require initial
      ordering stronger than chaos. Specifically, a large and initially randomly
      connected network of neurons rapidly develops several ergodically distinct
      subnetworks that operate independently. While the ergodic units operate
      independently and distinctly, they exhibit the property of equipotentially in
      that the specific events caused by an initial event are equally likely to be at
      any point in the ergodic set after very few synaptic events.

PMID- 12187780
TI  - Nitric oxide synthase inhibition suppresses wet dog shakes and augments
      convulsions in rats.
AB  - Electrical stimulation of limbic structures, pharmacological interventions, and
      getting wet induces wet dog shakes (WDS) in rats. WDS are often associated with
      the occurrence of seizures. In this study, we evaluated the effects of reduced NO
      production on physiologically (wetting)- or pharmacologically (kainic acid; KA)
      induced WDS and KA-triggered seizures. Following wetting, naive and saline
      treated rats displayed more WDS than rats treated with NO synthase (NOS)
      inhibitor, N omega-nitro-L-arginine (L-NA). In another experiment, WDS and
      seizures were monitored after KA treatment alone or in combination with L-NA.
      Again, NOS inhibition reduced the number of KA-triggered WDS but augmented the
      number and severity of seizures. Our results suggest that not only do
      physiologically- and kainate-induced WDS share a common mechanism that includes
      NO, but that there is also an antagonism between WDS and convulsions.

PMID- 12187781
TI  - Lateralized mineral content and density in distal forearm bones in right-handed
      men and women: relation of structure to function.
AB  - To test whether handedness has an asymmetric effect on distal forearm bone
      mineral content (BMC) and bone mineral density (BMD), and whether there is an
      effect of sex on these variables, the mean BMCs and BMDs in bilateral distal
      forearms were compared in right-handed men and women. It was expected that the
      BMC and BMD would be higher on the right than the left side in right-handers. The
      present results were consistent with this working hypothesis. Namely, the right
      BMCs were found to be significantly higher than left-BMCs for all regions of the
      bones studied. There were no sex differences either for the right-left BMCs or
      for the right-left BMDs. The results indicated that i) the relation of structure
      to function would also be valid outside the brain, ii) the mean BMCs, but not
      BMDs, were significantly higher in the right than the left arm at different
      distal forearm regions, and iii) there were no significant sex differences in the
      distal-forearm BMCs and BMDs.

PMID- 12187782
TI  - Maternal perinatal events as predictors of educational placement: computation of
      relative risk ratios.
AB  - This study examined the relative risk of perinatal complications in special
      education. The sample consisted of 634 children (normal children and those with
      mental retardation, learning disabilities, and emotional handicaps) whose mothers
      completed the Maternal Perinatal Scale (MPS). Seven MPS items significantly
      contributed to the prediction of the mentally retarded, learning disabled,
      emotionally handicapped, and regular education groups. The two significant
      discriminant functions correctly classified some 46% of the students correctly.
      When the separate disorders were collapsed to form a single group, 11 MPS items
      significantly contributed to the prediction of the special education and regular
      education groups. The linear composite from discriminant function analysis (DFA)
      correctly classified some 89% of the special education students. When MPS items
      were used as predictors, 90% of the special education students were correctly
      classified. Seven MPS factors comprised the discriminant function. Relative risk
      ratios were computed for each perinatal item. An overall relative risk of 6.35
      resulted, based on the linear composite of perinatal variables defined by the
      discriminant function, suggesting that a synergism of perinatal complications
      makes a child over 6 times more likely to be placed in special education. A
      second overall relative risk of 3.83 was derived from the linear composite of MPS
      items. This indicated that children with a perinatal history marked by this
      particular combination of perinatal complications were nearly 4 times as likely
      to require special educational services.

PMID- 12187783
TI  - Derived trail making test indices in a sample of alcohol abusers: demographic
      effects.
AB  - Derived indices on the Trail Making test (TMT), a test often used for screening
      cognitive impairments, were examined in a sample of alcohol abusers in drug abuse
      treatment programs. A mixed race sample of 1000 subjects was drawn from
      electronic files of data from the Drug Abuse Treatment Outcome Study (DATOS). The
      DATOS was a naturalistic, prospective cohort study that collected data from 1991
      1993 in 96 programs in 11 cities in the United States. Data were analyzed to
      determine the effects of demographic variables on derived indices created by
      adding, subtracting, multiplying, and dividing parts A and B of the TMT in this
      large treatment sample of alcohol abusers. The variables of age, ethnicity, and
      education were statistically significant for the total (A + B), interaction (A x
      B/100), and difference score (B-A) derived indices of the TMT. The ratio score
      (B/A) was only significant for education.

PMID- 12187784
TI  - Anesthesia and temperature effects on somatosensory evoked potentials produced by
      train stimuli.
AB  - OBJECTIVE: To determine the effect of anesthesia, temperature, and stimulus
      characteristics on the response of upper extremity somatosensory evoked responses
      (SSEP) to repetitive stimulation. METHODS: Pairs and trains of electrical stimuli
      were used to elicit the upper extremity SSEP, and the amplitudes of the N20-P22,
      N13, and Erb's point potentials produced by each stimulus were measured. The
      ratio of the amplitude of the response to each stimulus to that produced by the
      first stimulus in a given train was computed. Recordings were also made directly
      from the cortical surface in a single patient. RESULTS: There were only minimal
      effects of anesthesia, temperature, or stimulus characteristics on the amplitude
      ratios for the N13 and Erb's point potentials. The N20-P22 amplitude ratio
      demonstrated facilitation with interstimulus intervals in the 20-100 ms range and
      was markedly reduced with hypothermia. The degree of facilitation was strongly
      dependent on isoflurane and nitrous oxide concentrations. In response to
      stimulation with trains of four stimuli, increased amplitudes of the N20-P22
      complex were seen maximally with the second response while the third and fourth
      responses were of lower amplitude. CONCLUSIONS: There are strong effects of
      anesthesia and temperature on the cortical responses to repetitive stimulation of
      the upper extremity. Speculations on the origin of these effects were made.

PMID- 12187785
TI  - [Molecular mechanism of autophagy: the role of the Apg12 conjugation system].

PMID- 12187786
TI  - [Biochemistry and molecular biology of phenol sulfotransferases].

PMID- 12187787
TI  - [Cholesterol in lipid microdomains (rafts)--a new probe for cholesterol-rich
      membrane domains].

PMID- 12187788
TI  - [PPARs and signal transduction of prostaglandins].

PMID- 12187789
TI  - [alpha-Catenin: roles in cell-cell adhesion and cell fate determination].

PMID- 12187790
TI  - [DNA replication and DNA damage checkpoint control].

PMID- 12187791
TI  - [Structure and function of bacterial "super-channel" for macromolecule import].

PMID- 12187792
TI  - [Progress and utility of investigation of embryonal carcinoma: differentiation
      from embryonal carcinoma to cells related neuron owing to retinoic acid].

PMID- 12187793
TI  - [Growing age of population and its related subjects in Asia].

PMID- 12187794
TI  - [Neuroimaging--recent issues and future progresses].
AB  - Recent advances in the technology of non-invasive neuroimaging techniques,
      include X-ray CT, magnetic resonance imaging, positron CT, etc. The trend of
      neuroimaging is from the diagnosis of the brain structural change to the
      functional localization of the brain function with accurate topographical data.
      Brain activation studies disclosed the responsible regions in the brain for
      various kinds of paradigms, including motor, sensory, cognitive functions.
      Another aspect of brain imaging shows the pathophysiological changes of the
      neurological disorders, such as Alzheimer's disease by abnormal CBF or metabolism
      changes. It is very important to note that the neurotransmitter receptor imaging
      is now available for various kinds of transmitters. We recently developed a new
      tracer for nicotinic type acetylcholine receptor, which might be involved in the
      pathophysiology of Alzheimer's disease and its treatment. In the near future, we
      will be able to visualize the proteins in the brain such as amyloid protein,
      which will make us to diagnose Alzheimer's patients accurately, and with respect
      to neuroscience research, not only neuronal functional localizations but also
      relationship between them will become important to disclose the functional
      aspects of the brain.

PMID- 12187795
TI  - [The human genome project and genomic analysis of progeroid syndromes].

PMID- 12187796
TI  - [Search for genetic determinants of susceptibility to diabetes mellitus].

PMID- 12187797
TI  - [Examination of genetic susceptibility for essential hypertension].

PMID- 12187798
TI  - [Genetic susceptibility of COPD].

PMID- 12187799
TI  - [Physiological roles of endothelium-derived vasoactive peptides revealed by mouse
      genetics].

PMID- 12187800
TI  - [Clinical heterogeneity in elderly patients with diabetes mellitus].
AB  - There is considerable heterogeneity in elderly patients with diabetes mellitus.
      It is of clinical importance to assess such heterogeneous features in each
      elderly patient, because this would lead to a better setting of target glucose
      level in the management of diabetes. In the present study, diabetic subjects were
      clinically investigated from three different aspects; past, current and future.
      First, the "past" aspect represents how long and how high the hyperglycemia the
      patient has had. Our cross-sectional investigation showed a broad range of
      duration of diabetes as well as of degree of hyperglycemia, and as a consequence,
      diabetic complications were diverse. Second, the "current" aspect implies the
      degree of insulin deficiency and its resistance. According to our observation,
      elderly patients had diverse degrees of impaired insulin secretion, together with
      age-related resistance to insulin. Third, "future" aspect refers to the expected
      length of life, which largely depends on the current age. The complication status
      (not limited to diabetic complications), however, also affects clinical course
      and death rates, indicating diversity of life expectancies due to complications
      besides current age. Thus, the present analysis showed that elderly individuals
      with diabetes mellitus exhibit a remarkable heterogeneity. The present study also
      indicated the clinical merit of assessment with the three aspects; past, current
      and future, in assessing clinical diversity of elder patients with diabetes.

PMID- 12187801
TI  - [Insulin dependency of diabetes mellitus in the elderly].

PMID- 12187802
TI  - [Comprehensive geriatric assessment and treatment of elderly diabetic patients].
AB  - Because of diversities of physical, mental, and psychological functions as well
      as clinical and social backgrounds, comprehensive geriatric assessment (CGA) is
      of great importance in treating elderly diabetic patients. We addressed three
      issues as to functions important for the CGA. First, we assessed several domains
      of cognitive function in 213 elderly diabetic patients. Attention and visual
      memory in diabetic patients without vascular disease were impaired compared with
      non-diabetic controls after adjusting for age and sex using analysis of
      covariance. Multivariate analysis revealed that age, hyperglycemia, and the
      presence of cerebral infarction were independent determinants for the impairment
      of attention in the diabetic patients. The results suggest that glucose control
      is important for the maintenance of cognitive function in elderly diabetic
      patients. Secondly, we assessed positive well-being as a measure of psychological
      function using a PGC morale scale in 197 elderly diabetic patients without
      cerebrovascular disease at baseline and examined whether the low well-being
      affect the development of cerebrovascular disease in a 3-year longitudinal study.
      The results indicate that low well-being was an independent risk factor for
      cerebrovascular disease after adjusting conventional risk factors in elderly
      diabetic patients. Thirdly, as a physical function, we assessed 5-m walking speed
      for both usual and maximum walking in 64 diabetic patients. The walking speed
      decreased with age and correlated significantly with the knee extension power and
      functional reach. The result suggests that muscle-strength exercise and balance
      training as well as endurance exercises are necessary to improve age-related
      decreases in walking speed and for effective exercise in elderly patients. From a
      gerontological point of view, new strategies of elderly diabetes treatment
      including muscle strength exercise and psychological approaches should be
      established to improve physical, mental, psychological, and social functions as
      assessed by the CGA.

PMID- 12187803
TI  - [Non-invasive method of evaluating atherosclerosis in elderly patients].
AB  - Evidence has accumulated that impairment of vascular endothelial function is the
      initial step in the development of atherosclerosis. One important finding is the
      impairment of the release of the endothelium-dependent relaxing factor, which is
      now thought to be nitric oxide or its related substances, from endothelial cells.
      Flow-mediated dilatation (FMD) induced by reactive hyperemia has been know to be
      endothelium dependent, and this can be detected during reactive hyperemia by high
      resolution ultrasound in superficial arteries. Several coronary risk factors such
      as hypercholesterolemia, smoking and hyperhomocysteinemia have been reported to
      be significantly related with decreased FMD. A non-invasive technique using B
      mode ultrasonography can visualize and assess the lumen and vessel wall of the
      carotid artery. We analyzed Intima-media thickness (IMT) of the right common
      carotid artery using this method. IMT thickening consists of both an intimal
      atherosclerotic process and medial hypertrophy. Since IMT is increased in
      subjects with familial hypercholesterolemia and shows a progressive reduction
      with cholesterol-lowering treatment. IMT seems to be significantly related to the
      early phase of atherosclerosis. Ankle brachial pressure index and pulse wave
      velocity have been clinically applied to evaluate atherosclerosis. These methods
      are also introduced in this symposium.

PMID- 12187804
TI  - [Quality of life in elderly with atherosclerotic diseases].
AB  - To maintain the good quality of life in elderly, it is important to diagnose and
      asymptomatic advanced or prone to rupture atherosclerosis by using non-invasive
      techniques and it is also important to treat and prevent the progression of
      atherosclerotic disease. Comprehensive geriatric assessment is useful for
      maintain the good quality of life as well as evaluation of activity of daily
      life. Treadmill exercise test which protocol was arranged for Japanese elderly
      revealed high incidences of coronary ischemia susceptible patients in elderly
      diabetic patients. Concomitant measurement of blood pressure of lower extremities
      is also useful for early diagnosis of arteriosclerosis obliterence. Vascular
      endocrinological examination such as brain natriuretic peptide is expectable for
      early diagnosis of latent impairment of cardiac function. Evaluation of
      endothelial function by measuring flow mediated dilatation and evaluation of
      narrowing carotid artery by using ultrasound echocardiograph is useful. These
      examinations are expectable for future treatment of elderly patients.

PMID- 12187805
TI  - [Clinical significance of soluble interleukin-2 receptor as a putative systemic
      nutritional index in the elderly].
AB  - The clinical significance of a slight increase of serum soluble interleukin-2
      receptor (sIL2R) concentration in the stable elderly was investigated. Thirty
      five residents of nursing homes with physical impairment as a sequel to cerebral
      infarctions, without any inflammatory condition, anodyne or immunological
      treatment, were divided into two groups: 24 without overt or suspected malignancy
      (NC) and 11 with a history of malignancy (CA). Serological screening with
      measurement of sIL2 R concentrations was performed and numbers of lymphocytes
      with CD4, CD8 markers were determined. The NC group was divided into controls (n
      = 15, sIL2R < = 883 U/mL) and subjects demonstrating elevation (n = 9, NH), as in
      a previous study. Differences were found in serum concentrations of albumin,
      blood urea nitrogen, total cholesterol concentration, Pettigrew's prognostic
      nutritional index (PNI), as well as the ADL score, but not age or sex between NH
      and controls. Factor analysis in NC revealed serum creatinine and blood urea
      nitrogen concentrations to correlate positively, and serum albumin, total
      cholesterol concentrations, ADL score, PNI to correlate negatively to sIL2R.
      Differences were found in sIL2R, albumin, total protein, total cholesterol, beta
      lipoprotein, PNI between CA and controls, but correlations were not found in CA.
      Survival rate of controls over twenty-four months was better than that of NH, but
      not of CA. Our results suggest that a slight increase of concentration of sIL2R
      is related to subclinical systemic deterioration, especially with regard to
      nutrition, with a plausible connection to prognosis of the stable elderly without
      malignancy.

PMID- 12187806
TI  - [Effect of sustained release of theophylline on pulmonary physiologic function in
      elderly patients with chronic obstructive pulmonary disease].
AB  - We tested the effects of the sustained release of theophylline on the physiologic
      function of the respiratory system in elderly patients with chronic obstructive
      pulmonary disease (COPD). We measured the pulmonary function, static respiratory
      pressures, and ventilation during exercise, before and after the administration
      of sustained release of theophylline. Unifil, in 12 male COPD patients (mean age
      82.1 +/- 0.6 years old). Forced expiratory volume in one second was increased by
      the administration of 400 mg of Unifil, but not by 200 mg of Unifil, whereas the
      ratio of residual volume to total lung capacity was decreased by the
      administration of 400 mg Unifil. Maximum inspiratory pressure was significantly
      increased after the administration of 400 mg of Unifil. Dyspnea sensation during
      exercise assessed by the Borg scale was reduced by the administration of 400 mg
      of Unifil. These results indicate that the treatment with the greater dosage
      administration of Unifil is effective to improve the physiological function of
      the respiratory system in elderly patients with COPD, and it may be the treatment
      of choice for elderly COPD patients.

PMID- 12187807
TI  - [Evaluation of outcome based on platelet function in elderly patients with
      various diseases].
AB  - This study was conducted to clarify the relationship between the outcome of
      various diseases in elderly patients and platelet function. The outcome in 347
      consecutive patients aged 60 or older, who were treated without antiplatelet
      drugs on registration, was retrospectively studied after platelet aggregability
      tests. The mean age was 77.5 years (161 men and 186 women). The grading curve
      (GC) type, as an index of platelet aggregability, was determined
      spectrophotometrically with an aggregometer and adenosine-5'-diphosphate as an
      agonist. They were classified into three groups according to GC type: Group I
      with a GC type of -2 or -1 (n = 40), group II with a GC type of 0 or +1 (n =
      208), and group III with a GC type of +2 or +3 (n = 99). The mean follow-up
      period was 3.9 years. There were 3 deaths in group I, 33 in group II, and 30 in
      group III. Mean annual mortality rate was 2.1% in group I, 4.0% in group II, and
      7.5% in group III. Among causes of death, vascular events was seen in 15 patients
      of group III, although the most common cause of death was pneumonia in the three
      groups. The annual mortality rates due to vascular events were 0.7% in group I,
      0.6% in group II, and 4.2% in group III, indicating a significantly higher
      mortality rate in group III. Antiplatelet therapy was performed in approximately
      15% of each group during their clinical course, and, when they were excluded for
      survival analyses, annual mortality rate was also higher in group III than in
      groups I and II. Cox proportional hazards models for vascular death yielded a
      hazard ratio of 2.3 and 2.2 in the increased GC type and diabetes, respectively.
      These findings indicated that elderly patients with accelerated aggregability had
      higher mortality rates due to vascular events. Therefore, accelerated
      aggregability in the elderly suggested not only the progress of arteriosclerosis,
      but indications of antiplatelet therapy to prevent vascular events.

PMID- 12187808
TI  - [The usefulness of the water swallowing test and videofluorography in swallowing
      rehabilitation in patients with cerebrovascular disease].
AB  - It has been suggested that videofluorography (VF) is useful in the diagnosis of
      aspiration. The aim of this study was to investigate the usefulness of the water
      swallowing test and VF in swallowing rehabilitation in patients with
      cerebrovascular disease. Fifteen patients (mean age 72.9 +/- 2.3 years) were
      examined. The swallowing abnormality was assessed by the water swallowing test
      and VF. Patients with abnormal swallowing function on the water swallowing test
      (Group A, n = 4) showed aspiration and silent aspiration into the trachea on VF.
      However, patients suspected of dysphagia on the water swallowing test (Group B, n
      = 11) could swallow, demonstrating the disappearance of silent aspiration, with
      pooling of barium in the piriform sinus on VF. All patients in Group A could not
      ingest any food by mouth and received percutaneous endoscopic gastrostomy or
      intermittent oro-esophageal tube feeding. The swallowing function in Group B
      improved after swallowing rehabilitation. All patients in Group B could ingest
      food by mouth. These findings suggest that the water swallowing test is useful
      for quantitative assessment of swallowing disorder and for deciding on therapy of
      swallowing function.

PMID- 12187809
TI  - [A case of multiple myeloma with infiltration into skeletal muscle after
      injections of a granulocyte-colony stimulating-factor].
AB  - Multiple myelomas often occur in elderly people with complications due to aging.
      A 54-year-old man was first admitted with cerebral infarction, and multiple
      myeloma (IgG kappa, stage IIIA) occurred in November 1989 that was followed by
      partial remission after chemotherapy. The karyotype of the bone marrow cells was
      46, XY, and no p53 gene mutations were detected by polymerase chain reaction and
      single-strand conformation polymorphism analysis. Chemotherapy (melphalan 10 mg,
      vindesine 3 mg, ranimustine 150 mg, prednisolone 60 mg for 4 days) was performed
      in February 1999 because of aggravation of the myeloma. After daily subcutaneous
      injection of 50 micrograms of nartograstim for six days to treat neutropenia,
      soft tissues around the right eye were swelled gradually without redness,
      accompanied by elevation of the serum creatine-kinase concentration. The swelling
      disappeared, and the enzyme level normalized after discontinuation of
      nartograstim. In July, on the sixth day of daily subcutaneous injection of 75
      micrograms of filgrastim after the same chemotherapy, similar swelling of the
      soft tissues around the left eye became evident, and again this proved
      reversible. In July 2000, 40 mg of dexamethasone was infused, and after 5-day
      subcutaneous-injection of 75 micrograms of filgrastim daily, the right
      subclavicular soft tissue became swollen. He died of myocardial infarction, and
      autopsy revealed infiltration of myeloma cells into the right subclavicular
      muscle and bone marrow packed with myeloma cells. This case suggests that myeloma
      cells can proliferate and infiltrate into soft tissues on exposure to granulocyte
      colony stimulating factors.

PMID- 12187810
TI  - [A case of chronic obstructive pulmonary disease (COPD) followed by pulmonary
      rehabilition].
AB  - We report a 75-year-old woman with chronic obstructive pulmonary disease (COPD)
      suffering from cough, sputum, high-grade fever and dyspnea on effort. Her chest
      radiograph revealed an infiltrative shadow in the right lower lung field and her
      laboratory data showed marked inflammatory changes. Her arterial blood gas
      analysis showed marked hypoxemia and hypercapnia. After her laboratory data and
      general condition improved, we performed pulmonary rehabilitation for the patient
      for about 6 weeks. The program consisted of pursed lip breathing, diaphragmatic
      breathing, muscle stretch gymnastics, and walking. The 6-minute walking test
      distance increased from 170 m to 280 m. The minimum SpO2 during the 6-minute
      walking test increased from 88% to 91%. (O2 3 L/m) After discharge, she continued
      to receive home care from a visiting nurse specialized in respiratory medicine
      and 24 hour-monitoring of O2-compliance at home. She has not experienced acute
      exacerbation or re-hospitalization for 1 year. We conclude that home care service
      is effective to maintain stable conditions such as state of breathing, SpO2,
      vital signs, and activities of daily living for elderly COPD outpatients.

PMID- 12187811
TI  - [An autopsied case with a bicuspid aortic valve who had progressive angina
      pectoris and heart failure during follow-up of 27 years].
AB  - A Japanese man who died at age 85 had been followed since the age of 59, when he
      first presented. He had hypertension of 162/102 mmHg and a loud systolic murmur
      on his first visit. He had had an active daily life without any medication for
      the next 10 years. At the age of 72 he complained of mild chest discomfort on
      exercise. Although electrocardiography showed no abnormalities, echocardiogram
      showed calcified bicuspid aortic valve with mild stenosis. At the age of 81 the
      dyspnea and chest oppression were exacerbated, associated with marked ST
      depression on exercise electrocardiogram and restriction of aortic valve opening
      on echocardiograms. In the following years a gradual increase in QRS voltage and
      ST depression with T wave inversion were recorded on resting electrocardiograms
      and sharp increases in both left ventricular end-diastolic diameter and flow
      velocity at the aortic root were observed on echocardiograms. At the age of 85 he
      died of intractable heart failure with massive pleural effusion. Autopsy revealed
      marked hypertrophy and moderate dilatation of the heart (weight: 580 g). The
      bicuspid aortic valve had anterior-posterior cusps with a raphe on the anterior
      cusp. The mobility of the cusps was almost lost because of severe calcification
      and thickening. Severe stenosis was found near the orifice of the right coronary
      artery, but there were no significant ischemic myocardial lesions.

PMID- 12187812
TI  - [Half-solid enteral nutrient prevents chronic complications of percutaneous
      endoscopic gastrostomy tube feeding].
AB  - An 85-year-old woman was receiving enteral feeding via percutaneous endoscopic
      gastrostomy (PEG). The patient exhibited symptoms of gastro-esophageal reflux,
      leakage of nutrient from the PEG insertion point, vomiting, pyrexia, dyspnea when
      given nutrients and recurrent pneumonia. We therefore gave a half-solid nutrient,
      which was made by a mixture of agar powder and conventional liquid nutrient
      Immediately after starting the half-solid nutrient feeding via PEG, the patients
      no longer exhibited the above symptoms apart from mild pyrexia, which also
      vanished two weeks later. This case suggested that simply changing the fluidity
      of nutrients can contribute to a reduction of complications expected to occur in
      patients on PEG tube feeding.

PMID- 12187813
TI  - [Diagnosis of pulmonary tuberculosis in connection with the guideline for
      community-acquired pneumonia].
AB  - The decision when to make chest X-ray examination is important for early
      diagnosis of pulmonary tuberculosis and community-acquired pneumonia as well. And
      for early diagnosis of pulmonary tuberculosis, differential diagnosis with
      community-acquired pneumonia is important. For this reasons, guideline for the
      diagnosis and treatment of community-acquired pneumonia should include when to
      make chest X-ray examination, and how to exclude the possibility of pulmonary
      tuberculosis. For example, empiric choice of anti-microbial for apparent
      pneumonia should be an agent without anti-tuberculosis effect. Clinical
      evaluation of the effect of anti-microbial should be done carefully, because
      pulmonary tuberculosis can be clinically improved spontaneously. In the guideline
      for the diagnosis and treatment of community-acquired pneumonia could include the
      above-mentioned views on early diagnosis of pulmonary tuberculosis, the guideline
      could be much more helpful for the tuberculosis program.

PMID- 12187814
TI  - [Frequency of previous tuberculosis history in patients with and without active
      tuberculosis admitted to our hospital in 1980-83 and in 1997-99].
AB  - To study recurrence rate over a long period after recovery from previous
      tuberculosis history, we examined the frequency of previous tuberculosis history
      in patients who were admitted to our hospital in 1980-83 and in 1997-99 and the
      comparison was made between cases with and without culture-positive tuberculosis.
      The tuberculosis groups comprised of 297 patients in 1980-83 and 688 patients in
      1997-99. The non-tuberculosis groups (control groups) comprised of 373 patients
      in 1980-83 and 1092 patients in 1997-99 with non-tuberculosis diseases other than
      the tuberculosis-related diseases such as non-tuberculosis mycobacteriosis,
      pulmonary aspergillosis, bronchiectasis, chronic bronchitis and tuberculosis
      sequelae. The patients with viral chronic hepatitis previously operated and
      transfused were also excluded as they might be operated because of pulmonary
      tuberculosis in the era of surgical treatment for tuberculosis. In both
      tuberculosis and control groups, they had previous tuberculosis history most
      frequently when they were twenties. In the control groups, the frequency of
      previous tuberculosis history among cases admitted in 1980-83 and were born in
      1910-19, 20-29, 30-39, 40-49 were 15/84 (17.9%), 22/93 (23.7%), 11/77 (14.3%) and
      3/43 (7.0%), respectively, and those admitted in 1997-99 were 11/70 (15.7%),
      30/231 (13.0%), 28/288 (9.7%), and 10/230 (4.3%), respectively. In these 4 birth
      year groups, frequency of previous tuberculosis history among cases admitted in
      1997-99 were significantly lower than that admitted in 1980-83 (p < 0.05, one
      sided paired t-test), and the fact suggests that persons with tuberculosis
      history died earlier than those without it. In the tuberculosis groups, the
      frequencies of previous tuberculosis history among cases admitted in 1980-83 and
      were born in 1910-19, 20-29, 30-39 and 40-49 were 20/35 (57.1%), 31/58 (53.4%),
      19/48 (39.6%), and 11/53 (20.8%), respectively, and those among cases admitted in
      1997-99 were 30/99 (30.3%), 58/125 (46.4%), 22/102 (21.6%) and 17/136 (12.5%),
      respectively. The frequency of previous tuberculosis history among cases admitted
      in 1997-99 was significantly lower than that admitted in 1980-83 (p < 0.01) as
      was the case in the control groups. As recurrence within 5 years had occurred in
      only 4 out of 113 tuberculosis patients (3.5%) in the above-mentioned 4 birth
      year groups, almost all tuberculosis patients were assumed to have recovered
      completely from previous tuberculosis. Comparison between the recurrence rate
      from previous tuberculosis and the incidence rate from the remotely infected
      persons without previous tuberculosis history in the same birth year group can be
      done by calculating the prevalence of tuberculosis infection for each birth year
      group using a model of annual risk of tuberculosis infection appropriate for
      Japanese. The ratios between the recurrence rate from previous tuberculosis
      patients and the incidence rate from remotely infected persons without previous
      tuberculosis history were 4.71, 2.33, 1.78 and 1.11 in 1980-83 and 1.84, 3.99,
      1.80 and 1.11 in 1997-99 for groups born in 1910-19, 20-29, 30-39 and 40-49,
      respectively. The ratio did not change systematically with time in these groups,
      indicating the recurrence rate did not change with time more than ten years after
      recovery from previous tuberculosis. The ratio was about 3 for groups born in
      1910-19 and 20-29 and 1 for group born in 1940-49. Almost all patients born in
      1940-49 could receive chemotherapy for tuberculosis in their twenties, while most
      of the patients born in 1910-29 could not. Therefore, the above-mentioned fact
      may reflect the recurrence rate of patients treated successfully with
      chemotherapy is almost the same as the incidence rate from remotely infected
      persons, while that the recurrence rate from previous tuberculosis patients
      spontaneously recovered is 3 times higher than the incidence rate from remotely
      infected persons.

PMID- 12187815
TI  - [The study on the duration of treatment in the standard short course chemotherapy
      containing pyrazinamide].
AB  - Based on the results of a questionnaire for the tuberculosis specialists in the
      whole country, we investigated whether the standard short course chemotherapy
      containing pyrazinamide (four drugs regimen: HRZE/S) were given for adequate
      duration. The results of a questionnaire revealed that the duration of treatment
      was prolonged in 60% of 848 cases due to several reasons. The reasons for the
      longer duration of treatment were (1) complication of other disease, (2) delay in
      the improvement on chest X-ray, (3) delay in negative conversion of bacilli, (4)
      drug resistance, (5) patient's request, and (6) others. According to our own
      experience in the National Dohoku Hospital for the past four years, the duration
      of therapy was prolonged in 86% of cases treated with the four drugs regimen, and
      in 64% of cases with the three drugs regimen (HRE/S). Four drugs regimen was
      preferred for severer cases and the three drugs regimen for older patients. The
      reasons for the prolonged duration of treatment in our hospital were similar to
      those in the results of a questionnaire in the whole country. We recognized that
      the treatment was prolonged due to several meaningless reasons such as "no
      particular reason", "anxiety on relapse" and "patient's request". In order to
      decide the adequate duration of treatment, it is needed to know the relapse rate
      in cases with the short course chemotherapy and its relationship with
      complications. It is hoped to establish the guideline for tuberculosis treatment
      including the duration of treatment based on the results of detailed clinical
      studies.

PMID- 12187816
TI  - [Understanding level on tuberculosis among hospital nurses].
AB  - Tuberculosis control in big cities should be focused on preventing defaulting
      from treatment, and the prevention of the emergence of multi-drug resistant
      tuberculosis, and the improvement of treatment success rate. Since it is needed
      to organize continued case management system starting from hospitalization,
      discharge, management of regular drug taking at outpatient clinics and final
      cure, close collaboration should be made between hospital nurses and public
      health nurses. For this purpose, there should be no difference about the
      understanding on tuberculosis control between clinical and public health nurses.
      This research was aimed to examine "How much interest and recognition do hospital
      nurses have about tuberculosis control." The Aichi Nursing Association cooperated
      with this research. The results showed that 60% of tuberculosis ward nurses were
      more than forty years old, and they have served more than ten years in TB word.
      The levels of understanding on tuberculosis among nurses working in tuberculosis
      hospitals were much higher than those in general hospitals. However, it is
      necessary to organize a collaboration system between hospitals and public health
      center to improve TB case management.

PMID- 12187819
TI  - [Complications and their treatments in eyes with high myopia].

PMID- 12187818
TI  - [A study of INH 0.1 microgram/ml resistant M. tuberculosis strains assessed by
      BrothMIC MTB-1 method].
AB  - In the antimycobacterial susceptibility test for INH using the egg-based Ogawa
      media, 3 concentrations (0.1, 1, or 5 micrograms/ml) of INH were used, and 1
      microgram/ml was used as a critical concentration for INH resistance. However, it
      was controversial whether INH 0.1 microgram/ml resistant M. tuberculosis was
      clinically significant or not. We investigated the MIC values of INH 0.1
      microgram/ml resistant strains by using BrothMIC MTB-1 method, and 115 strains of
      M. tuberculosis confirmed by DNA-prove test were used. The distribution of MIC
      values of 115 strains determined by Ogawa INH susceptibility test was shown in
      figure. By BrothMIC MTB-1 method, they were classified into 3 groups;
      susceptible, low resistant and high resistant groups. The mean MIC value of INH
      0.1 microgram/ml resistant M. tuberculosis was estimated to be 4.53 micrograms/ml
      with its 95% confidence interval 3.21-5.85 micrograms/ml, and they were
      determined as "resistant" in BrothMIC MTB-1 method. These results supported the
      idea that patients with INH 0.1 microgram/ml resistant M. tuberculosis strains
      should be regarded as clinically "resistant".

PMID- 12187817
TI  - [A case of tuberculosis pleuritis developing contralateral pleural effusion
      during anti-tuberculosis chemotherapy, falling into chronic respiratory failure].
AB  - The patient was a 74 year-old male presenting right pleural effusion with mild
      fever. His temperature was 37.0 degrees C. Culture of a pleural biopsy specimen
      revealed Mycobacterium tuberculosis, although culture of sputum and pleural
      effusion were negative. Therapy was begun with 300 mg of isoniazid (INH) per day,
      600 mg of rifampicin (RFP) per day, and 1200 mg of pyrazinamide (PZA) per day.
      His temperature improved temporarily. One week after beginning of the therapy he
      had a fever over 38.0 degrees C. On the 17th day after starting chemotherapy, a
      chest radiological examination showed left pleural effusion in which numerous
      lymphocytes were found but Mycobacterium tuberculosis was negative. We assumed
      that the left pleural effusion was due to a paradoxical reaction to the anti
      tuberculosis chemotherapy. After 3 days' discontinuation, the same regimen was
      resumed with an addition of prednisolone, but bilateral pleural effusion remained
      and the case finally fell into chronic respiratory failure.

PMID- 12187820
TI  - [The quality of life in patients with pathologic myopia].
AB  - PURPOSE: To evaluate the functional status of daily life and the quality of life
      of pathologic myopia patients. METHODS: A cross-sectional study was conducted
      using data from pathologic myopia patients(n = 211) and control subjects(n =
      144). The influence of the disease on the daily life and the quality of life of
      patients were evaluated using a self-rating questionnaire. The questionnaire
      covered the full range of the status of patients' daily life and the quality of
      life of pathologic myopia patients, including daily tasks depending on visual
      acuity, social and emotional handicaps, and cognition of disease. RESULTS: The
      functional status of daily life and the quality of life of patients was reduced
      compared with control subjects. The influence of pathologic myopia on the
      patients' daily lives was primarily the result of three major factors: handicap,
      disability, and support. All three correlated with the quality of life, the
      degree of handicap having the strongest correlation. CONCLUSION: The functional
      status of daily life and the quality of life of patients was reduced; this
      reduction in quality of life was attributed to disability and handicap caused by
      pathologic myopia.

PMID- 12187821
TI  - [Cytokine mRNA expression in vernal keratoconjunctivitis].
AB  - BACKGROUND: Cytokines play an important role in chronic allergic eye disease.
      OBJECTIVES: We examined how many kinds of cytokines are in giant papillae of
      vernal keratoconjunctivitis(VKC). METHODS: We resected giant papillae from 6
      patients with VKC, and studied mRNA expression of cytokines in them with the
      reverse transcriptase-polymerase chain reaction(RT-PCR). The cytokines were
      interleukin(IL)-1 beta, IL-1 receptor antagonist (IL-1 RA), IL-2, IL-4, IL-5, IL
      6, IL-8, interferon (INF) gamma, tumor necrosis factor(TNF) alpha, TNF beta,
      transforming growth factor(TGF) beta 1, and TGF beta 2. RESULTS: In 5 cases,
      expression of IL-1 beta was positive. Expression of IL-1 RA, IL-5, IL-6, IL-8,
      TGF beta 1, and TGF beta 2 was positive in 6 cases. TNF alpha was positive in 4
      cases. IL-4 and INF gamma were positive in 3 cases. IL-2 and TNF beta were
      negative in all patients. CONCLUSION: These results suggest that the Th2
      cytokines play more important roles than the Th1 cytokines in VKC inflammation.

PMID- 12187822
TI  - [A novel mutation of the type 1 optic atrophy(OPA1) gene in a Japanese family
      with OPA1].
AB  - PURPOSE: To report a novel mutation of the type1 optic atrophy(OPA1) gene in a
      Japanese family with OPA1 and to describe the clinical features of this family.
      METHODS: Standard ocular examinations were performed on the proband and his two
      affected sons. The DNA sequence of all exons and splice sites of the OPA1 gene
      was determined to detect mutations. RESULTS: The proband and his sons had a
      heterozygous mutation of the OPA1 gene in the third nucleotide of intron 12(IVS12
      + 3A-->T). Clinically, each patient had reduced visual acuity(onset within the
      first 6 years of life) and optic nerve pallor. The proband showed a central
      scotoma and generalized dyschromatopsia. This is the first report of OPA1 gene
      mutation in Japanese patients with familial optic atrophy. CONCLUSIONS: A
      mutation of the OPA1 gene was detected in a Japanese family with OPA1, which
      follows the same pattern as reported in Western countries. It is suggested that
      mutations of the OPA1 gene contribute to the development of optic nerve atrophy
      regardless of ethnic groups. Screening for the OPA1 gene mutation will be useful
      for diagnosis of OPA1 in Japanese patients.

PMID- 12187823
TI  - [Eyestrain induced by stereogram on 3-D display--differences between types of
      correction].
AB  - PURPOSE: We investigated eyestrain in normal subjects induced by gazing at a
      random-dot stereogram on a parallax barrier system 3-D display. METHODS: The 41
      subjects were divided into 4 groups according to the type of correction. Near
      point of accommodation, accommodative relaxation, and contraction times were
      measured with an accommodo-polyrecorder before and after a stereoscopic visual
      load, and 15 min and 30 min after a rest. The subjective symptoms were assessed
      by a 7-point rating questionnaire at the same time as the measurements. RESULTS:
      After 15 min of sustained visual load, the near point of accommodation was
      prolonged significantly in the groups without correction and with soft contact
      lenses(SCL), and accommodative contraction and relaxation times were significant
      delayed in the groups without correction, with hard contact lenses(HCL), and with
      SCL but not in the group with spectacles. These changed values of accommodation
      returned to their previous value following the rest. Significant increase in the
      rating questionnaire was found in the subjective symptoms of "eyestrain", "eye
      heaviness", "clouding", "eye dryness" and "irritation of eyes" after loading in
      the groups without correction, with HCL, and with SCL. In the spectacle group,
      there was no significant change in the subjective symptoms of "clouding" and "eye
      dryness". CONCLUSION: From these results, it is concluded that gazing at
      stereoscopic images on the parallax barrier system 3-D display causes severer
      eyestrain in cases of correction with contact lenses and in uncorrected cases
      than in cases with spectacles.

PMID- 12187824
TI  - [Morphological findings in progressive esotropia with high myopia].
AB  - PURPOSE: Esotropia with high myopia is due to elongation of the eyeball, which
      becomes too large to fit within the muscle cone. To demonstrate the elongation,
      we measured the size of the eyeballs. SUBJECTS AND METHODS: Five patients with
      esotropia with high myopia(myopic esotropia group), 8 patients with high myopia
      without esotropia(high myopia group), and 10 controls(control group) were
      examined. Using magnetic resonance imaging, we measured the outer axial length
      and the maximum transverse size of the eyeballs. RESULTS: The outer axial
      length(mean +/- standard deviation) was greater in the order of the myopic
      esotropia group(31.6 +/- 1.59 mm), the high myopia group(27.9 +/- 2.22 mm), and
      the control group(23.7 +/- 1.59 mm) (p < 0.01). The maximum transverse size was
      also greater in the order of the myopic esotropia group(25.0 +/- 0.99 mm), the
      high myopia group (24.9 +/- 1.27 mm), and the control group(23.1 +/- 1.38 mm).
      The outer axial length of the eyeballs in the myopic esotropia group was
      significantly longer than in the high myopia group and the control group, and the
      maximum transverse size was significantly longer than in the control group.
      CONCLUSIONS: The elongation of the eyeballs of the myopic esotropia group was
      demonstrated. A high incidence of esotropia may occur when the outer axial length
      of high myopia is longer than 30 mm.

PMID- 12187825
TI  - [Canaliculitis caused by Actinomyces in a case of dry eye with punctal plug
      occlusion].
AB  - BACKGROUND: We report a case of canaliculitis caused by Actinomyces odontolyticus
      in a case of dry eye with punctal plugs. CASE: A 64-year-old female with
      Sjogren's syndrome type of dry eye developed lacrimation, congestion in the lower
      palpebral conjunctiva and corneal epithelial damage in her right eye 30 months
      after punctal plug occlusion. After removal of the plug from lower punctum in her
      right eye, white material exuded from the punctum. However, even after the
      removal of a plug, corneal epithelial keratopathy did not get worse, implying
      that the granulation tissue formed by the plug completely occluded the
      canaliculus. Actinomices odontolyticus was cultured from the white material. One
      week after topical antibiotic treatment, conjunctival congestion and irritation
      were resolved. CONCLUSION: This report indicates the possibility of canaliculitis
      as a complication of punctal plug occlusion. Careful observation is necessary
      after punctal occlusion with punctal plugs.

PMID- 12187826
TI  - [A case of follicular lymphoma derived from the conjunctiva].
AB  - BACKGROUND: Follicular lymphoma, derived from ocular adnexa as defined by World
      Health Organization Classification of neoplastic diseases of the hematopoietic
      and lymphoid tissues, is quite rare in Japan. CASE: A 65-year-old woman visited
      our clinic for treatment of a conjunctival tumor in the left eye. FINDINGS:
      Incisional biopsy revealed that the lesion was a lymphoma with well-defined
      follicles, and it was L 26(CD20) and BCL-2 positive immunohistochemically. Flow
      cytometric analysis showed that more than 70% of the cells were double positive
      for CD10 and CD20. Southern blot hybridization demonstrated gene rearrangement
      bands in the immunoglobulin gene JH region. The chromosome had a translocation
      t(14, 18) (q32, q21). Systemic evaluation detected no other lymphoma. CONCLUSION:
      The lesion was a follicular lymphoma derived from conjunctival tissue. Additional
      examinations such as flow cytometric analysis, gene analysis, and chromosome
      examination were useful for differential diagnosis of marginal zone B cell
      lymphoma of mucosa associated lymphoid tissue type and benign reactive lymphoid
      hyperplasia.

PMID- 12187827
TI  - [Roles of nitric oxide (NO) on LH-induced ovulation and steroidogenesis in the in
      vitro perfused rat ovary and on the regulation of ovarian blood flow in vivo].

PMID- 12187828
TI  - [Analysis of CD4+CD25+ T cells in transgenic rats carrying the env-pX gene of
      HTLV-I].

PMID- 12187829
TI  - [Helicobacter pylori adherent to MKN-45 cell].

PMID- 12187830
TI  - [Cooperative role of osteopontin with type I collagen on the metastasis of murine
      melanoma cells].

PMID- 12187832
TI  - [Evaluation of physiological accumulation of [11C]acetate in normal prostate
      using positron emission tomography].

PMID- 12187831
TI  - [Enhanced expression of matrix metalloproteinase-9 (MMP-9) under hypoxic and
      nutrient-deprived conditions].

PMID- 12187834
TI  - [3-phosphoglycerate dehydrogenase (3PGDH) expression in supporting cells of the
      rat peripheral nervous system and its upregulation after nerve injury].

PMID- 12187833
TI  - [Dominant negative HIF-1 alpha reduces tumorigenicity of a human pancreatic
      cancer cell line].

PMID- 12187835
TI  - [Overview of computer-aided diagnosis].
AB  - Computer-aided diagnosis (CAD) systems have been developed in many institutions.
      CAD is able assist radiologists and physicians in detecting lesions and in
      differentiating benign from malignant lesions on medical images. The output from
      CAD can be used as a "second opinion" to assist radiologists in their
      interpretations and improve diagnostic accuracy. It is important to note that CAD
      is not designed for the automated diagnostic system. A few commercial CAD systems
      have recently been developed by venture companies, with pre-marketing approval
      having been obtained from the U.S. Food and Drug Administration (FDA). It is
      clear that CAD has practical value in radiologic diagnosis. In this paper, the
      background of CAD research and important topics, including the usage of an image
      database and methods of evaluating the performance of typical CAD schemes, are
      discussed. The number of CAD researchers in Japan is not yet sufficient.
      Radiological technologists who have a strong interest in CAD research will be
      good partners for radiologists in developing CAD schemes.

PMID- 12187837
TI  - [Pathologic/high-resolution CT correlation of focal lung lesions 5 mm or less in
      diameter: detection and identification by multidetector-row CT].
AB  - PURPOSE: To clarify the limitations of multidetector-row CT (MDCT) in detecting
      focal lung lesions of 5 mm or less in diameter by pathologic/high-resolution CT
      (HRCT) correlation. MATERIALS AND METHODS: Twenty-two patients who underwent both
      preoperative HRCT of the entire lobe using MDCT (MD-HRCT) and lobectomy for
      primary (n = 21) or metastatic (n = 1) lung tumor were studied. The author
      attempted to locate any focal lung lesions other than the main tumor throughout
      the resected and sliced specimens and to identify the opacities corresponding to
      the macroscopic lesions on MD-HRCT before histopathologic evaluation. Then two
      observers without pathologic information attempted to detect the lesions on MD
      HRCT. RESULTS: Ninety-one lesions of 5 mm or less in diameter were found in 15
      patients. Histopathologically, 13 lesions were classified as bronchioloalveolar
      carcinoma (BAC), 38 as atypical adenomatous hyperplasia (AAH), 9 as reactive
      hyperplasia (RH), 19 as inflammatory lesion (INF), 8 as solid lesion (SL), and 4
      as showing no organizing change. The author, who had knowledge of the gross
      pathologic examinations, identified the opacities at rates of 100%, 82%, 56%,
      42%, and 88% for BAC, AAH, RH, INF, and SL, respectively. The rates of lesion
      detection in the absence of knowledge of the pathologic examinations were 85%,
      58%, 22%, 32%, and 75% for BAC, AAH, RH, INF, and SL, respectively. The rates of
      identification and detection of lesions more than 3 mm in diameter were 90% and
      57%, respectively, while those of lesions less than 2 mm in diameter were 71% and
      35%, respectively. CONCLUSIONS: MD-HRCT proved to be useful in detecting focal
      lung lesions of 5 mm or less in diameter; however, it is still difficult to
      detect lesions of less than 2 mm in diameter.

PMID- 12187836
TI  - [Computer-aided diagnosis of breast cancer].
AB  - Computer-aided diagnosis (CAD) is generally defined as a diagnosis made by a
      radiologist who takes into account computer output as a "second opinion". The
      computer output usually indicates the location of suspicious lesions such as
      microcalcifications or masses in mammograms, and also provides quantitative
      analysis of potential lesions, yielding measures such as the likelihood of
      malignancy. The purpose of CAD is to improve diagnostic accuracy and the
      consistency of radiologists' image interpretation by using such computer output
      as a guide. This article provides a brief overview of some CAD schemes used for
      breast cancer.

PMID- 12187838
TI  - [Evaluation of usefulness of bone SPECT for lumbar spondylolysis].
AB  - The purpose of this study was to evaluate the usefulness of 99mTc-MDP SPECT (bone
      SPECT) for lumbar spondylolysis. We analyzed 11 cases with 17 lesions. All cases
      were compared using plain radiography, computed tomography (CT), planar bone
      scintigraphy (PBS), and bone SPECT. Four lesions that showed a wide defect on CT
      were negative on bone SPECT and may have been chronic lesions. Thirteen lesions
      that were positive on bone SPECT were narrow or showed no defect on CT and may
      have been early lesions. Two cases showed no defect on CT but were positive on
      bone SPECT, and one of them progressed to bilateral spondylolysis after one year.
      This may have been a very early lesion. Thus bone SPECT is useful for the
      diagnosis of lumbar spondylolysis, especially in its early stage.

PMID- 12187839
TI  - [Myocardial fatty acid imaging with 123I-BMIPP in patients with chronic right
      ventricular pressure overload: clinical significance of reduced uptake in
      interventricular septum].
AB  - Regionally reduced 123I-BMIPP uptake in the interventricular septum (SEP) is
      observed in some patients with chronic right ventricular (RV) pressure overload.
      We studied the significance of this finding by comparing it with mean pulmonary
      arterial pressure (mPAP). 123I-BMIPP SPECT imaging was carried out in 21 patients
      with pulmonary hypertension (PH; 51(+)-14 years; 11 men and 10 women; 7 with
      primary pulmonary hypertension, 11 with pulmonary thromboembolism, and 3 with
      atrial septal defect). mPAP ranged from 25 to 81 mmHg (49 +/- 16 mmHg). Using a
      midventricular horizontal long-axis plane, regional BMIPP distributions in the RV
      free wall and SEP were estimated by referring to those in the LV free wall. Count
      ratios of the RV free wall and SEP to the LV free wall (RV/LV, SEP/LV) were
      determined by ROI analysis. RV/LV showed a linear correlation with mPAP (r =
      0.42). However, SEP/LV was inversely correlated with mPAP (r = -0.49). When
      SEP/RV was compared among three regions of SEP in each patient, basal SEP/RV was
      most sensitively decreased in response to increased mPAP (r = -0.70). These
      results suggest that the assessment of septal tracer uptake in 123I-BMIPP SPECT
      imaging is useful for evaluating the severity of RV pressure overload in patients
      with PH.

PMID- 12187840
TI  - Investigation of radiation quality and doses in Japanese routine mammography.

PMID- 12187841
TI  - The role of endothelial cell dysfunction in the cardiovascular mortality of RA.
AB  - Rheumatoid patients present clinically with chronic inflammatory immune arthritis
      but die of the same cardiovascular (CVS) disease as the normal population. Recent
      studies emphasize the increased frequency and earlier development of CVS
      involvement in RA. The mechanisms of this accelerated atherosclerosis are the
      subject of active research. The hypothesis that rheumatoid vasculitis is a major
      factor has been pursued through studies in primary systemic vasculitis. These
      reveal diffuse endothelial dysfunction occurring across a spectrum of vasculitis
      and involving more than one vascular bed. This may relate to cytokines such as
      TNF alpha that are both prominent in rheumatoid inflammation and important in the
      upregulation of endothelium in innate immune responses. Endothelial injury or
      dysfunction is widely accepted as the initial factor in atheroma. Its occurrence
      in vasculitis leads us to propose a model for RA where this dysfunction is the
      essential first step on which other factors, ranging from adverse lipid profiles
      to specific T-cell subsets, may build accelerated atherogenesis related to the
      rheumatoid inflammation.

PMID- 12187842
TI  - AECA and ANCA in patients with premature atherosclerosis.
AB  - Autoimmunity is suggested to play a pathogenetic role in premature
      atherosclerosis. Since atherosclerosis and vasculitis seem pathogenetically
      related, we hypothesized that ANCA, an important antibody in vasculitis, plays a
      role in atherosclerosis as well. We therefore investigated the prevalence of ANCA
      in patients with premature atherosclerosis and related the presence of these
      antibodies to levels of AECA and markers of inflammation. METHODS & RESULTS: In a
      cohort of 286 patients with premature atherosclerosis the prevalence of ANCA was
      5.6% (16/286). All had perinuclear ANCA. More females were ANCA-positive (8M/8F
      vs. 200M/70F, p = 0.03). In a nested case-control study, comparing the 16 ANCA
      positive patients with 32 controls, levels of AECA were higher in the first (7.32
      +/- 0.91U vs. 5.52 +/- 0.41U, p < 0.05). CONCLUSION: ANCA does not seem to play a
      major role in premature atherosclerosis. Whether elevated levels of AECA in ANCA
      positive patients with premature atherosclerosis reflect more extended vascular
      disease remains to be determined.

PMID- 12187843
TI  - Immune activation as effect modifier of atherogenesis in chronic infection.
AB  - Although no study has proven that infections cause atherosclerotic disease,
      findings suggest that exposure to infections such as Chlamydia pneumoniae,
      Helicobacter pylori, and bacterial infections related to periodontal disease or
      smoking might influence the development of heart, carotid, and peripheral
      vascular disease. Epidemiological data convincingly demonstrate risk for
      atherosclerotic disease associated with bacterial infection and endotoxemia;
      however, the independent contributions to disease and pathogenic mechanisms of
      endotoxin remained elusive. Investigation into this relation tested the
      correlation between endotoxin and neopterin. Data indicated that neopterin, which
      reflects immune activation of monocytes/macrophages, functions as atherogenic
      effect modifying factor on the effects of endotoxin. We hypothesize that immune
      activation via induction of endotoxin hyperresponsiveness determines the
      atherogenic potential of Gram-negative infections.

PMID- 12187844
TI  - The molecular control of angiogenesis.
AB  - Angiogenesis is a key event in a broad range of pathological conditions including
      both diseases with an enhanced and insufficient angiogenesis. Angiogenesis is
      often initiated with vasodilation accompanied by an increase in vascular
      permeability. After destabilization of the vessel wall and degradation of the
      surrounding extracellular matrix, extravasation of plasma proteins provides a
      provisional scaffold for the migration of endothelial cells. Endothelial cell
      proliferation and migration themselves are under tight control by a balance of
      angiogenesis inducers and inhibitors. A large number of angiogenic factors work
      together in a highly coordinated manner to induce endothelial cell outgrowth and
      the formation of functional vessels. On the other hand, angiostatic factors may
      play a critical role in the pathogenesis of ischemic diseases and contribute to
      the termination of physiological angiogenesis. Angiogenesis ends with the
      recruitment of pericytes and smooth muscle cells, which stabilize the newly
      formed vessel. The rapid increase in the knowledge about the molecular mechanisms
      of angiogenesis has led to first treatment trials in diseases with both enhanced
      and reduced angiogenesis. Although initial results are promising, much more work
      has to be done to consider anti-angiogenic or pro-angiogenic approaches as
      reliable therapeutic tools.

PMID- 12187845
TI  - Anti-beta 2-glycoprotein I autoantibodies and atherosclerosis.
AB  - beta 2-Glycoprotein I (beta 2-GPI) is a major antigen for antiphospholipid
      antibodies (aPL) present in patients with antiphospholipid syndrome (APS). We
      previously reported that beta 2-GPI specifically binds to oxidized low-density
      lipoprotein (oxLDL). Further, a ligand specific for beta 2-GPI, oxLig-1, purified
      from the extracted lipids of oxLDL was identified as 7-ketocholesterol-9
      carboxynonanoate (i.e., 9-oxo-9-(7-ketocholest-5-en-3 beta-yloxy) nonanoic acid)
      OxLig-1 was recognized by beta 2-GPI and subsequently by anti-beta 2-GPI
      autoantibodies. Binding of liposomes containing oxLig-1 to macrophages were
      significantly enhanced in the presence of both beta 2-GPI and an anti-beta 2-GPI
      autoantibody derived from (NZW x BXSB) F1 mouse, an animal APS model, or from APS
      patients. Anti-beta 2-GPI autoantibodies derived from APS patients with episodes
      of arterial thrombosis were detected in ELISA, using a solid phase beta 2-GPI
      complex with oxLig-1. It was also reported that LDL-receptor-deficient mice that
      were fed a chow diet and immunized with beta 2-GPI had an accelerated
      atherosclerosis and that beta 2-GPI was abundantly expressed within
      subendothelial regions and intimal-medial borders of human atherosclerotic
      plaques. All of these observations strongly suggest that autoimmune atherogenesis
      linked to beta 2-GPI interaction with oxLDL and autoantibodies may be present in
      APS.

PMID- 12187846
TI  - Cecile and Oskar Vogt: the visionaries of modern neuroscience.

PMID- 12187847
TI  - [Morphometric analysis of wheat and rye zygotes during maturation].
AB  - The size of cell, nucleus, and nucleolus was measured and the nucleus-to
      nucleolus ratio was determined during zygote maturation in durum and soft wheat
      and rye under intravarietal pollination as well as under crossing of durum wheat
      with soft wheat and rye. The fluctuations of cell, nucleus, and nucleolus volumes
      during zygote maturation were observed. The curves percent ratio of these volumes
      to corresponding volume of egg cell have two peaks. There are differences between
      hybrid zygotes and parental forms in these indices.

PMID- 12187848
TI  - [Hybridization and genetic control of esterase in apricot].
AB  - Inheritance of esterase was studied in nine segregating progenies. It was
      established that fast migrating components are controlled by two loci, Est-1
      (monomeric alpha-esterase) and Est-2 (dimeric beta-esterase). Their polymorphism
      is determined by three active alleles, a, a', b for Est-1 and a, b, c for Est-2,
      respectively. Allelic frequencies and heterozygosity of loci in ecological
      geographical groups and Central Asian subgroups were estimated. Genetic control
      of esterase in stone fruits was proposed for the first time.

PMID- 12187849
TI  - [Peculiarities of the influence of chemical and physical factors on cytogenetic
      indices of root meristem in Pisum sativum L].
AB  - The results of comparative analysis of cytogenetic effects of various chemical
      and physical factors on meristemic cells of field pea (Pisum sativum L.) are
      presented. Cytogenetic effects of aluminum, cadmium and selenium compounds as
      well as X-ray irradiation were studied. Cytogenetic indices were investigated for
      different doses of the above factors and peculiarities of their influence on the
      ratio of mitotic phases were analyzed. The increasing in the proportion of cells
      at the specific mitotic stage was revealed. There were anaphase stage for
      aluminum chloride, prophase stage for cadmium chloride, meta- and anaphase stages
      for sodium selenate, and telophase stage for X-rays. Investigated chemical
      elements may be ranged according to their ability to induce the aberrant anaphase
      frequency in the row: Se (from 3.75 x 10(-6) M) > A1 (from 3.86 x 10(-5) M) > Cd
      (from 8.44 x 10(-5) M). Maximal experimental dose of X-ray irradiation (9.03 x
      10(-3) C/kg) induces the frequency of chromosome aberration similar to those
      induced by maximal experimental doses of aluminum and selenium (3.86 x 10(-4) M
      and 8.34 x 10(-6) M).

PMID- 12187850
TI  - [Intra- and interspecies differences in the ISSR-PCR patterns of bumble bee
      (Hymenoptera: Bombinae)].
AB  - Variation in the ISSR patterns was studied in queens of five species of bumble
      bee habitating on the territory of Ukraine and Belarus. Species-specific
      characteristics were obtained for B. sylvarum, B. lapidarius, B. pascuorum, B.
      terrestris, and B. hortorum with using (GTG)7A and (AGC)6G as primers. Some ISSR
      markers were common for the groups of species. From 73 to 100% ISSR markers were
      invariant within the species. Individual characteristics of B. terrestris from
      geographically distant populations from Kiev and Minsk Oblasts were similar. The
      level of intraspecific variation was different among the species. Taking into
      account intraspecific constancy of the major ISSR-PCR patterns and in the same
      time their susceptibility to individual differences we proposed these markers
      could be used to elucidate some complicated questions of bumble bee taxonomy.

PMID- 12187851
TI  - [Conjugation resistance to Fusarium graminearum Schwabe with multiple molecular
      forms of some enzymes in winter wheat].
AB  - Electrophoretic spectra of multiple molecular forms of peroxidase (EC 1.11.1.7),
      superoxide dismutase (EC 1.15.1.1), phenol oxidase (EC 1.10.3.1), and cytochrome
      oxidase (EC 1.9.3.1) in seedlings of two aegilops species and eleven genotypes of
      bread winter wheat differing in the level of their resistance to Fusarium
      infection are presented. Several izoforms of peroxidase, phenol oxidase, and
      superoxide dismutase correlate with the level of resistance to Fusarium.
      Infection of plants with the pathogen enhances expressiveness of some multiple
      forms of enzymes. Such response to infection in less pronounced in the sensitive
      genotypes as compared with that in the resistant ones.

PMID- 12187852
TI  - [Comparative analysis of the genetic structure of hybrid populations of European
      toads of the genus Bombina (Oken, 1816) from Ukraine and Croatia].
AB  - The comparative analysis of hybrid populations of toads Bombina bombina and B.
      variegata from Ukraine and Croatia revealed the essential differences in their
      genetic structure. The population composition and the direction of genetic
      introgression are determined initially by the ecological factors (the locality
      type, the country relief). The clear predominance of the red-bellied toad Bombina
      bombina was found in two cases: in the lowland populations and in the big
      samples. The second parental species, B. variegata, predominates in the highlands
      and in the small samples, respectively.

PMID- 12187853
TI  - [The increasing mutagenic effect of nitrosoguanidine under the influence of
      modified bases during inhibition of repair AGT enzyme in mammalian somatic cells
      in vitro].
AB  - Gene mutations were studied on human cells SL68, XP12BE and chinese hamster cells
      Blld-ii-FAF28C1237. All the cells were sensitive to purine base analogs and were
      characterized by a high rate of O6-alkylguanine-DNA-transferase (AGT) activity.
      Inhibiting AGT activity by O6-benzylguanine considerably increases the frequency
      of mutants induced by the alkylating agent MNNG. Transitions of the GC-->AT type
      are the dominant mutations in the coding region of the hprt gene. The mechanism
      of DNA lesion repair by the AGT enzyme differs significantly from the excision
      repair.

PMID- 12187854
TI  - [Main morphofunctional types of blast cell nucleoli in non-Hodgkin lymphoma and
      benign hyperplasia].
AB  - Expression of main morphofunctional types of blast cell nucleoli in lymphomas and
      benign hyperplasia was compared in the cytological material of 38 patients for
      revealing additional differential cytological signs of malignant transformation
      of lymphoid cells. Cytogenetic criteria of malignant transformation of the blast
      population of lymphoid cells were determined.

PMID- 12187855
TI  - [Signal systems of plant immunity].
AB  - Plants can recognise the penetrating pathogen and respond to the attack with an
      array of defense reactions. Signal transduction from receptor in plasma membrane
      to genome is necessary to activate these reactions. Plant cell signaling systems
      which take part in signal transduction were discovered and identified recently.
      The obtained results suggest that plant cells have complex and well coordinated
      signal network which regulates their immune potential.

PMID- 12187856
TI  - [Genetic and biochemical mechanisms of ontogenetic and phylogenetic adaptation].
AB  - Results of the scientific research of genetic mechanisms of ontogenetic and
      phylogenetic adaptation in the department of genetics and molecular biology of
      the Odessa national university (ONU) are summarized. The new concept of genetic
      adaptation and adaptive heterosis is proposed. The evidence are presented that
      not only selection of selectively valuable alleles of the structural genes of
      enzymes, but also of gene-modifiers of the gene products are involved in the
      adaptation of D. melanogaster populations to environmental conditions. As a
      result, the sets of coadaptation alleles--adaptation complexes of genes (ACG),
      which are specific to the selective factors, are formed in persons of the
      population.

PMID- 12187857
TI  - [Atrial fibrillation--state of the art].

PMID- 12187858
TI  - [Epidemiology of atrial fibrillation].
AB  - FREQUENCY: Atrial fibrillation is the most frequent sustained arrhythmia,
      especially in the elderly. The incidence accounts for 2% past the age of 40
      years, 6% over 70, an approximately 15% over 90 years old. PATHOGENESIS: Primary
      cause in "idiopathic" atrial fibrillation is differentiated from secondary causes
      of cardiac and non-cardiac origin. Important predictive cardiovascular diseases
      to develop atrial fibrillation are coronary heart disease, hypertension or
      rheumatic heart disease. Electrophysiological mechanism behind atrial
      fibrillation is a reentry circuit. The clinical symptoms are influenced by the
      conducted ventricular heart rate and the loss of atrial contraction. TREATMENT
      AND PROGNOSIS: The need for a therapeutic approach--either for recurrence of
      sinus rhythm or heart rate control--is mainly determined by the quality of life.
      Quality of life, functional capacity and maximum oxygen consumption are improved
      if sinus rhythm is reestablished. Finally, mortality is double as high if atrial
      fibrillation is present. Whether mortality is directly influenced by atrial
      fibrillation or fibrillation is considered as more or less the subsequent
      arrhythmia for an underlying disease is still under investigation.

PMID- 12187859
TI  - [Atrial fibrillation: molecular biology bases].
AB  - BACKGROUND: Atrial fibrillation is the most frequent form of sustained
      arrhythmia. In most cases the arrhythmia is acquired, in rarer cases it may occur
      as a familial disease with a autosomal dominant pattern of inheritance. Recent
      advances in molecular biology and genetics have had a major impact on our
      understanding of the mechanisms responsible for the initiation, maintenance and
      chronification of the arrhythmia. Recently, the chromosomal locus for familial
      atrial fibrillation has been mapped to chromosome 10q22-q23, however, so far the
      causative gene has not been identified. ATRIAL REMODELING: Atrial fibrillation
      itself modifies atrial electrical properties in a way that promotes the
      occurrence and maintenance of the arrhythmia, in other words "atrial fibrillation
      begets atrial fibrillation". The principle stimulus for atrial remodeling is the
      rapid atrial rate. PERSPECTIVES: It is hoped that the results of future studies
      will not only further improve our understanding of the mechanisms underlying
      atrial fibrillation but may also help to develop new therapeutic strategies.

PMID- 12187860
TI  - [Atrial fibrillation: pathophysiology].
AB  - BACKGROUND: Although several classical studies seemed to provide clear ideas on
      the pathophysiology of atrial fibrillation, current concepts have to be modified
      on the basis of more recent findings. REENTRANT CIRCUITS: Based on the findings
      of Garrey and of Moe & Abildskov, atrial fibrillation has long been considered as
      the prototype of an arrhythmia being caused by multiple, random reentrant
      circuits, the number of which would determine the stability of the reentrant
      process. Local refractory and conduction properties would determine the size of
      individual circuits, a hypothesis quite convincing with respect to
      refractoriness, but so far hard to prove with respect to conduction. The finding
      that rapid atrial rates shorten atrial refractory periods and reverse rate
      adaptation (atrial remodeling) has coined the phrase "atrial fibrillation begets
      atrial fibrillation", indicating that any atrial tachyarrhythmia modifies the
      substrate in a way that favors reentry. With intracellular calcium overload being
      the initial trigger, down-regulation of genes encoding for calcium channels seems
      to primarily account for atrial remodeling. Primarily neglected concepts on the
      pathophysiology of atrial fibrillation suggesting single, meandering circuits or
      focal activity have regained attention. Atrial fibrillation as a random
      phenomenon is questioned not only by the dominant role of the left atrium for the
      maintenance of the arrhythmia, but also by most recent data demonstrating a
      spatio-temporal periodicity in activation patterns. Finally, ablation studies
      have provided convincing evidence that there is a subset of patients with focal
      or at least focally induced atrial fibrillation.

PMID- 12187861
TI  - [Remodeling in atrial fibrillation].
AB  - BACKGROUND: Atrial fibrillation is associated with alterations in atrial
      electrophysiology that facilitate the initiation and persistence of the
      arrhythmia. This process was termed electrical remodeling in atrial fibrillation.
      The underlying cellular and molecular mechanisms have intensively been
      investigated over the past few years in patients with atrial fibrillation and in
      different experimental models. The results, that have substantially improved the
      understanding of the pathophysiology of atrial fibrillation, are reviewed.
      CELLULAR AND MOLECULAR MECHANISMS: On the cellular level, atrial fibrillation
      leads to a strong shortening and an impaired rate adaptation of the action
      potential as well as to changes in action potential morphology. Atrial
      fibrillation is associated with an altered gene expression of the L-type calcium
      channel (ICa,L) and of potassium channels (Ito, IK1, IKACh). The molecular
      mechanisms of intraatrial conduction slowing are less well understood, changes in
      the expression or distribution of gap junction proteins or a decrease of the fast
      sodium inward channel (INa) have been reported in some studies. A trigger of
      initiation for electrical remodeling is an overload of the cytoplasm with Ca2+
      and a consecutive decrease of the systolic calcium gradient, furthermore changes
      in calcium-handling proteins are detectable in atrial fibrillation. CONCLUSION:
      These changes in the cellular and molecular milieu importantly determine the
      clinical course and the efficacy of therapeutical interventions in atrial
      fibrillation. The clinical relevance and potential new therapeutic approaches are
      discussed in the last part.

PMID- 12187862
TI  - [Prevention of arterial thromboembolisms in patients with atrial fibrillation].
AB  - BACKGROUND: Patients with atrial fibrillation have a 5% risk per year for
      ischemic stroke. The aim of antithrombotic therapy is to prevent arterial
      thromboembolic events. As anticoagulation increases the frequency of bleeding,
      the risk and benefits of this therapy have to be assessed for each patient.
      PATIENTS AT RISK: The patients can be classified as low risk (< 2% stroke/year),
      medium risk (2-6% stroke/year), and high-risk patients (> 6% stroke/year).
      Parameters for the risk stratification are the patient age and cardiac as well as
      non-cardiac diseases. PREVENTION: Patients with a low risk need no
      anticoagulation or can take aspirin. Patients with a high risk should receive
      oral anticoagulation with an INR range from 2.0 to 3.0. Newer guidelines
      recommend also for patients with intermediate level of stroke risk instead of
      aspirin the prescription of oral anticoagulation. Patients with a medium risk can
      interrupt the oral anticoagulation before surgery or invasive diagnostic
      procedures for 1 week, patients with a high risk should receive heparin. 3-4
      weeks before and after cardioversion the standard therapy is oral
      anticoagulation.

PMID- 12187863
TI  - [Pharmacological therapy of atrial fibrillation and atrial flutter].
AB  - BACKGROUND: Despite the increasing availability of nonpharmacological treatment
      options for atrial fibrillation, drug therapy targeted at restoration and
      maintenance of sinus rhythm, or aimed at symptomatic ventricular rate control
      remains the mainstay of therapy for the majority of patients. METHOD: Available
      data suggest that these two treatment approaches yield similar responder rates
      with regard to symptomatic improvement. RESULTS: Detailed results from major
      prospective studies investigating the prognostic effects of different atrial
      fibrillation treatment modalities are expected to become available soon. At
      present, however, the choice of the primary treatment strategy, i.e. rate control
      or rhythm control, still remains upon the clinical decision and expertise of the
      treating physician. Cardioversion by means of external biphasic shock delivery
      has shown to effectively convert atrial fibrillation to sinus rhythm in more than
      90% of patients. Pharmacological cardioversion, in contrast, has a far lower
      success rate and may be followed by severe complications mandating in-hospital
      administration with the majority of drug regimens. For the maintenance of sinus
      rhythm, the proarrhythmic side effects of Class I antiarrhythmic drugs currently
      limit their use to those patients without any structural heart disease. Clinical
      investigation of newer "pure" Class III drugs have shown to excite considerable
      prolongation of ventricular repolarization duration resulting in a significant
      risk for torsade-de-pointes tachycardia. Betablockers are beneficial in many
      clinical situations associated with the occurrence of atrial fibrillation, such
      as heart failure, arterial hypertension and coronary artery disease. These
      substances, however, do not seem to improve cardioversion rates and their effect
      in maintaining sinus rhythm is only moderate. Patients with structural heart
      disease in whom maintenance of sinus rhythm is strongly desired, therefore, are
      left to amiodarone therapy. The cardiac safety profile as well as the proven
      effectiveness are unsurpassed by any other available drug at present. This paper
      reviews major studies published during the last decade implementing recent
      guidelines regarding pharmacological rate control, cardioversion and maintenance
      of sinus rhythm and the approach towards patients suffering from paroxysmal
      atrial fibrillation.

PMID- 12187864
TI  - [Atrial fibrillation: stimulation and pacemaker therapy].
AB  - Pacing therapy is well established in all cases of symptomatic bradyarrhythmic
      atrial fibrillation. In paroxysmal or persistent atrial fibrillation, the
      implanted dual chamber pacemaker device should incorporate an automatic mode
      switching algorithm. Mode switch in case of atrial fibrillation detection avoids
      pacemaker mediated rapid ventricular pacing during an atrial tachyarrhythmia and
      allows to perform dual chamber pacing during phases of sinus rhythm which is the
      preferable mode due to improved hemodynamics, rate adaptation, lower progress in
      atrial fibrillation burden and a lower rate of thromboembolic events as compared
      to ventricular pacing. PERSPECTIVE: The possibility to prevent from atrial
      fibrillation recurrencies by pacing is currently under investigation. Various
      methodological approaches, for example multisite or alternate single site pacing,
      preventive pacing algorithms or hybrid- and even triple-therapy concepts are used
      for that purpose. Due to the theoretical point of view, that all these pacing
      interventions may reduce atrial fibrillation but also have the potential to act
      in a proarrhythmic manner, the data from adequately designed trials is of major
      importance: Septal pacing and preventive pacing algorithms seem to have a
      beneficial effect in a limited number of so far available studies. CONCLUSION: In
      clinical practice, preventive pacing and/or placement of the atrial lead in a
      septal position should therefore be available in those patients with a
      conventional pacing indication in addition to symptomatic recurrent atrial
      fibrillation. Preventive pacing is so far with a significant and not-predictable
      amount of non-responders no "early" stage of therapy in patients with recurrent
      symptomatic atrial fibrillation and no additional conventional pacing indication.

PMID- 12187865
TI  - [Intraoperative high frequency current ablation as therapy of atrial
      fibrillation. The Berlin modification].
AB  - BACKGROUND: The Cox-maze procedure combined with an operation for organic heart
      disease is highly successful in the elimination of chronic atrial fibrillation.
      However, it prolongs significantly the aortic cross-clamp and operating time. In
      this study, a simplified left atrial maze procedure, a short procedure performed
      using a surgical radiofrequency ablation probe, is added to elective open-heart
      procedures in patients with atrial fibrillation. PATIENTS AND METHODS: 95 adults
      with atrial fibrillation (duration, 6 months to 33 years) underwent elective open
      heart operations (isolated valve procedures or coronary artery bypass grafting, n
      = 51 patients; combined procedures, n = 44 patients) combined with intraoperative
      radiofrequency ablation of the left atrium. The postoperative follow-up period
      ranged from 1 to 24 months (mean, 8 months). Possible predictors for persistent
      postoperative atrial fibrillation were determined among 40 variables by
      univariate and multivariate analyses. RESULTS: Intraoperative radiofrequency
      ablation prolonged the aortic cross-clamp time for 6-14 minutes (mean, 11
      minutes). Freedom from atrial fibrillation was 100% intraoperatively, 30% at 1
      week after operation, and 84% and 84% at 6 and 12 months postoperatively. The
      only predictor of postoperative atrial fibrillation was the presence of coronary
      artery disease (odds ratio, 7.5; 80% confidence interval, 2.24-25.13).
      CONCLUSIONS: Intraoperative radiofrequency ablation of the left atrium combined
      with an operation for organic heart disease effectively eliminates atrial
      fibrillation without significant prolongation of the aortic cross-clamp and
      operative time. The presence of coronary artery disease decreases the success
      rate during the first 6 postoperative months.

PMID- 12187866
TI  - [Primary catheter ablation in atrial fibrillation].
AB  - BACKGROUND: Primary catheter ablation of atrial fibrillation is a new and
      curative option for the treatment of patients with drug-refractory atrial
      fibrillation. It is aiming at a long-term restoration of sinus rhythm and thereby
      causing a coordinated atrial contraction. ABLATION METHODS: Two different
      ablation strategies have been established: The "trigger elimination" tries to
      identify triggering atrial extrasystoles (mostly within the pulmonary veins),
      followed by focal ablation or isolation within the pulmonary veins. The
      "substrate modification" changes by long linear radiofrequency-induced lesions
      the ability of the atrial myocardium to sustain atrial fibrillation. VALUATION:
      Both treatment options still have to prove their effectiveness in carefully
      monitored follow-up, before they can be offered to the general patient population
      with atrial fibrillation.

PMID- 12187867
TI  - [Secondary catheter ablation of atrial fibrillation].
AB  - BACKGROUND: In patients with drug-refractory atrial fibrillation there are some
      non-pharmacologic therapeutic options for heart rate control or recurrence
      prophylaxis that do not primarily aim at the induction or maintenance of atrial
      fibrillation itself. AV NODE ABLATION AND MODULATION: Using radiofrequency
      ablation AV nodal conduction can be completely interrupted (AV node ablation) or
      partly impaired (AV node modulation), which allows subsequent control of the
      effective ventricular rate (if necessary by pacer maker implantation). Atrial
      fibrillation, however, does continue undisturbed in the atria, with its
      associated risk of thromboembolic complications. SECONDARY CATHETER ABLATION: The
      other option of a secondary catheter ablation approach to atrial fibrillation
      consists of a combination of antiarrhythmic medication using Class Ic or III
      antiarrhythmics and its conversion of atrial fibrillation to isthmus-dependent
      atrial flutter, which can subsequently be treated by curative bi-directional
      isthmus blockade. Termination of the antiarrhythmic medication may lead to
      reoccurrence of atrial fibrillation. OBJECTIVES: The review discusses the
      mentioned options for secondary catheter ablation of atrial fibrillation together
      with possible indications, success rates and potential complications.

PMID- 12187868
TI  - [Atrial fibrillation in heart failure].
AB  - BACKGROUND: Atrial fibrillation is a common arrhythmia in patients with
      congestive heart failure caused by left ventricular dysfunction and is associated
      with significant morbidity and possibly increased mortality rates. It occurs with
      increasing frequency as the severity of heart failure increases. TREATMENT: As
      therapeutic options, two basic strategies are available: rhythm control with or
      without pharmacological manipulation to increase the chance of successful
      cardioversion and to maintain sinus rhythm, and rate control with
      anticoagulation. So far, a clear benefit of one of these two strategies over the
      other has not been demonstrated for patients with atrial fibrillation generally,
      nor have there been convincing data for the subgroup of heart failure patients.
      Traditionally, digoxin has been used in patients with heart failure and atrial
      fibrillation; however, it has no proven potential to restore sinus rhythm and is
      slow and not very effective in rate control requiring the addition of another
      rate-limiting agent, preferably a beta-blocker or calcium antagonist. Amiodarone
      has been evaluated in numerous clinical trials in patients with heart failure and
      appears to be safe and effective in terms of conversion to sinus rhythm,
      maintenance of sinus rhythm as well as control of ventricular rate. Dofetilide
      may be another option in patients with atrial fibrillation and heart failure,
      although a direct comparison with amiodarone is lacking. The problem with all
      antiarrhythmic drugs specifically in patients with heart failure is their
      toxicity. Because of their proarrhythmic effects, Class I antiarrhythmics are
      contraindicated in patients with heart failure. Torsades de pointes is the most
      serious adverse effect of sotalol and dofetilide. Amiodaron has less
      proarrhythmic risk but has numerous non-cardiac toxicities that require frequent
      monitoring. CONCLUSION: Overall, due to a low efficacy rate and high
      proarrhythmic risks, an ideal antiarrhythmic agent for patients with atrial
      fibrillation and heart failure does not exist, and drug selection should be
      highly individualized. In patients with chronic atrial fibrillation and heart
      failure, anticoagulation with warfarin for prevention of thromboembolic events is
      mandatory.

PMID- 12187869
TI  - [Influence of ecological environment on the physiological status of students from
      northern regions].

PMID- 12187870
TI  - [The duration of exercise tolerance in terms of circulatory indices in the
      inhabitants of the Sakha republic (Yakutia) within a ten-year period].

PMID- 12187872
TI  - [Mathematical description of sensorimotor reaction time distribution].

PMID- 12187871
TI  - [Effect of plasma and cellular factors on aggregation of erythrocytes from
      different age populations].

PMID- 12187873
TI  - [Morphophysiological features of the heart exertion in 3- to 4-year old
      children].

PMID- 12187874
TI  - [Ontogeny of motor synergism and the causes of their disturbances with age].

PMID- 12187875
TI  - [Neurophysiological and neuropsychological indicators of the efficiency of the
      rehabilitation of patients with parkinsonism].

PMID- 12187877
TI  - [EEG dynamics in women during pregnancy and after delivery].

PMID- 12187876
TI  - [Unimanual reaction time during comparison of lateralized verbal stimuli: the
      features of interhemispheric interactions related to subjects gender].

PMID- 12187878
TI  - [Study of thresholds of motor evoked responses during transcranial magnetic
      stimulation in healthy subjects and patients with brain tumors].

PMID- 12187879
TI  - [A method of diagnosis of the functional state of afferent pathways of the spinal
      cord by magnetic stimulation].

PMID- 12187880
TI  - [Psychophysiological mechanisms and consequences of autogenous stress].

PMID- 12187881
TI  - [Age-related dynamics of recognition of the orientation of rectangular gratings
      upon the resolution limit of the visual system].

PMID- 12187882
TI  - [Heart rate variability in healthy six- to sixteen year old children].

PMID- 12187884
TI  - [Analysis of heart rate variability based on the graph method].

PMID- 12187883
TI  - [Use of a physiological monitoring model for comprehensive evaluation of adaptive
      capacities in schoolchildren during learning activity. Part I. Influence of
      various motor activity regimens on cardiac rhythm induces in junior
      schoolchildren].

PMID- 12187885
TI  - [Electromyographic parameters of muscle fatigue in patients with parkinsonism].

PMID- 12187886
TI  - [Oxygen demand and energy cost of intense muscular activity in humans].

PMID- 12187887
TI  - [Cardiovascular responses to isometric muscle tension in healthy subjects and in
      patients with neurocirculatory dystonia].

PMID- 12187889
TI  - [Curietherapy (brachytherapy) in restenosis following coronary angioplasty:
      panacea or sorcerer's apprentice technique?].

PMID- 12187888
TI  - [Role of the initial state in response of the hemostatic system to heavy
      exercise].

PMID- 12187890
TI  - [History of residential medical education].

PMID- 12187891
TI  - [Epidemiology and etiology of atrial fibrillation].
AB  - Atrial fibrillation is the most common sustained rhythm disturbance, with a
      heterogeneous presentation, occurring in the presence or absence of detectable
      heart disease or related symptoms, evolving in paroxysmal, persistent or
      permanent forms. Prevalence and incidence are mainly depending on age and
      congestive heart failure. Atrial fibrillation is frequently observed in elderly
      population. Prognosis can be poor, owing to the risk of embolic events, mainly
      ischaemic strokes, with a rate of 5% yearly, and to an increased mortality rate,
      about twice that of persons in normal sinus rhythm. Atrial fibrillation can
      present as an isolated arrhythmia (20 to 40% of cases) or be associated with an
      underlying cardiac disease which exerts a main influence on prognosis.

PMID- 12187892
TI  - [Mechanisms of atrial fibrillation].
AB  - Atrial fibrillation occurs because of a complex interaction between an
      arrhythmogenic substrate, triggers factors and the autonomic nervous system.
      Underlying fundamental mechanisms are multiple, can cohabit and include
      schematically: multiple wavelet, stable microreentry, macro single meandering
      spiral wave reentry and focal atrial fibrillation arising from the pulmonary
      veins. More over, new concepts have emerged like the atrial fibrillation-induced
      electrical and structural remodeling which favors its own perpetuation.
      Experimental studies have shown a complex interaction between anatomical
      particularities of the atria and the activation fronts dynamic. All this recent
      progress open new and more efficient therapeutic perspectives for patients
      enduring atrial fibrillation.

PMID- 12187893
TI  - [Diagnostic approaches and complications of atrial fibrillation].
AB  - Atrial fibrillation is the most frequently occurring cardiac arrhythmia. Its mode
      of clinical presentation is varied. Frequently asymptomatic, it is nonetheless
      often responsible for tiredness, dyspnea or palpitations. More rarely, it
      presents with one of its two major complications: cardiac failure or a systemic
      thromboembolic event, often cerebral.

PMID- 12187894
TI  - [Cardioversion in atrial fibrillation].
AB  - For cardioversion of atrial fibrillation 2 techniques are available:
      pharmacological and electrical. Pharmacological cardioversion is effective,
      especially when the duration of arrhythmia is shorter than 7 days. In contrast,
      for long duration of fibrillation electrical external cardioversion is the
      technique of choice. The success rate ranges from 64 to 96%. The development of
      new defibrillators delivering biphasic waveforms is associated with an increase
      in the success rate of cardioversion. For patients where external cardioversion
      has failed, internal cardioversion should be proposed. One major concern is
      prevention of embolic complications. For this purpose 2 strategies are equally
      effective: 1.3-week anticoagulation with warfarin; 2. short-duration (2 days)
      heparin treatment is sufficient if the presence of a left atrial thrombus has
      been ruled out with a transoesophageal echocardiocardiogram.

PMID- 12187895
TI  - [Antiarrhythmic drugs in atrial fibrillation].
AB  - Antiarrhythmic drugs in atrial fibrillation are relatively old and have well
      specified indications. Class I antiarrhythmic drugs (IA: quinidine, disopyramide;
      IC: cibenzoline, flecainide, propafenone) are first indicated in patients without
      history of myocardial infarction and heart failure. In this last case, a b
      blocker or amiodarone are indicated. Amiodarone is also indicated after failure
      of class I antiarrhythmic drugs. The association of class I antiarrhythmic drugs
      or amiodarone with a small dose of b-blocker is suitable if possible. However,
      the association of amiodarone with half-dose of a class I antiarrhythmic drug
      should remain rare, because the prognosis of chronic atrial fibrillation is
      unknown; the benefits to risks ratio of antiarrhythmic treatment should be
      discussed for each patient.

PMID- 12187896
TI  - [Antithrombotic drugs in atrial fibrillation].
AB  - Stroke and peripheral thrombo-embolism are common in all forms of atrial
      fibrillation which is responsible for a hypercoagulable state. Clinical and
      echocardiographic risk stratification allow therapeutic recommendations among the
      different antithrombotic strategies used in randomized studies (adjusted-dose
      oral anticoagulant, aspirin or a combination of aspirin and low-dose oral
      anticoagulant) in agreement with recent guidelines from the European and American
      associations of cardiology for the managMent of patients with atrial
      fibrillation.

PMID- 12187897
TI  - [Ablative methods for atrial fibrillation].
AB  - Surgery and catheter-based ablation are the only curative approaches of atrial
      fibrillation. Since 1994, several ablative techniques based on 2 different
      concepts have been developed: modification of the substrate with long linear
      lesions to prevent fibrillation maintenance; and foci ablation to prevent
      fibrillation initiations. The latter is more frequently used now as the
      clustering of foci in pulmonary veins allows their isolation. The presence of
      numerous foci in some patients is responsible for more complex procedures and
      limits the success rate to 70%. In spite of this limit and because of a
      reasonable complication rate, this procedure compares favourably to His bundle
      ablation in young patients with symptomatic and drug-resistant paroxysmal atrial
      fibrillation.

PMID- 12187898
TI  - [Atrial fibrillation: rhythm or rate control?].
AB  - For many years it has been considered that it was necessary, whenever possible,
      to cardiovert atrial fibrillation and to maintain the sinus rhythm with
      antiarrhythmic drugs. There are many theoretical advantages to this maintenance
      of the sinus rhythm. Nevertheless the choice of the drugs used to maintain rhythm
      is often difficult and the therapeutical index of these drugs may be poor. It is
      necessary to avoid class I antiarrhythmic drugs in patients with congestive heart
      failure and coronary artery disease. In these cases, only sotalol and amiodarone
      can be used. The safety index of these drugs being low, plain rate control with
      persistence of atrial fibrillation has been proposed as a treatment alternative.
      Several drugs may be used: calcium inhibitors, beta-blockers, digitalis. It is
      always necessary to associate anticoagulation: of course if rate control is
      chosen, but also if rhythm control is obtained, owing to the possible risk of
      relapse. Several trials of comparison between these 2 strategies have been
      recently performed. Available results show no clear superiority of a strategy
      above the other but there is a tendency towards a lower mortality in the rate
      control group.

PMID- 12187899
TI  - [Development of pedagogy].

PMID- 12187900
TI  - [Principal pregnancy complications. Gravid hypertension--pre-eclampsia syndrome].

PMID- 12187901
TI  - [Suicide risk in adults. Identification and management].

PMID- 12187902
TI  - [Medical certificates. Death and legislation. Organ procurement and legislation].

PMID- 12187903
TI  - [Acute infection of soft tissue (abscess, whitlow, phlegmon of soft tissues)].

PMID- 12187904
TI  - [Feeding and nutritional requirements of infants and children].

PMID- 12187906
TI  - Advancing Laboratory Practice in Haematology VI. 12-15 September 2001, Jersey,
      Channel Islands. Abstracts.

PMID- 12187905
TI  - [Bites and stings. Prevention of rabies].

PMID- 12187907
TI  - Professor Vaclav Paces celebrates his 60th birthday. From bacteriophage genome
      sequencing to integrated genomics.

PMID- 12187908
TI  - [Current issues in animal protection. Continuing education event of the ATF
      Specialty Group for Animal Protection and the Institute of Animal Hygiene,
      Protection and Behavior of the Hannover Veterinary School. 27-28 September 2001.
      Proceedings].

PMID- 12187909
TI  - The need for interval appendectomy: how many times do we need to kill the
      gimmick?

PMID- 12187910
TI  - Ongoing clinical trials.

PMID- 12187911
TI  - Renal interstitial hydrostatic pressure and sodium excretion in hypertension and
      pregnancy.
AB  - The kidney plays an important role in the long-term regulation of blood pressure
      and extracellular fluid volume through the regulation of sodium and water
      excretion. Increases in renal perfusion pressure (RPP) cause a potent natriuretic
      stimulus, referred to as 'pressure natriuresis', which is an important mechanism
      in the regulation of extracellular fluid volume and blood pressure. In
      normotensive animals, increases in RPP are transmitted to the renal interstitium
      and result in increases in renal interstitial hydrostatic pressure (RIHP), as
      well as in sodium and water excretion. However, pressure natriuresis is
      significantly attenuated in hypertensive and pregnant normotensive rats.
      Furthermore, this response is associated with an attenuated increase in RIHP with
      increases in RPP, suggesting that the renal interstitial compliance is greater in
      hypertension and during pregnancy than in normotensive non-pregnant states. In
      the absence of other mechanisms, this attenuated pressure natriuretic response
      can lead to volume retention. However, volume expansion also increases RIHP and
      sodium excretion. It is proposed that a compensatory increase in the natriuretic
      sensitivity to increases in RIHP counterbalances the volume retention that
      results from the attenuated pressure natriuresis in hypertensive rats, and thus
      may play an important role in maintaining normal plasma volume in these animals.
      Likewise, it is also proposed that the attenuated relationship between blood
      pressure, RIHP and sodium excretion that is observed during normal pregnancy is
      due to an increase in the compliance of the renal interstitium and leads to a
      reduction in sodium excretion and the gradual gestational volume expansion.
      During pregnancy, RIHP does not increase immediately due to the large renal
      interstitial compliance and therefore the increased sensitivity of the
      natriuretic response to increases in RIHP does not occur, and gradual volume
      expansion continues during normal pregnancy. However, the increased sensitivity
      of the natriuretic response to increases in RIHP takes effect only after the
      necessary volume is retained for a normal pregnancy. Below this requisite volume
      expansion, the increase in RIHP is not sufficient to activate the exaggerated
      natriuretic sensitivity to increases in RIHP. Failure of these adaptive
      mechanisms during pregnancy can lead to disturbances in the regulation of plasma
      volume which, in turn, can affect amniotic fluid volume and fetal growth and may
      result in premature labour and intrauterine growth restriction, as well as pre
      eclampsia.

PMID- 12187912
TI  - Systolic blood pressure: an underestimated cardiovascular risk factor.
AB  - Classification of the severity of hypertension and recommendations on the blood
      pressure values to be achieved during antihypertensive drug treatment have for
      decades been based on diastolic values. It is now clear, however, that systolic
      blood pressure is by no means less important. This paper will focus on the
      following sets of evidence: (1) that epidemiologically a selective elevation of
      systolic blood pressure has a major prevalence in the elderly population; (2)
      that isolated systolic hypertension carries a marked increase in the risk of
      cardiovascular disease and that even in systo-diastolic hypertension this risk
      may be more closely related to systolic than to diastolic blood pressure; (3)
      that treatment of systolic hypertension greatly reduces cardiovascular
      complications and that in all conditions this reduction is related to the
      treatment-induced reduction in systolic blood pressure to a degree similar to or
      superior to the relationship with the reduction in diastolic blood pressure; and
      (4) that in the hypertensive fraction of the population, control of systolic
      blood pressure is achieved much less often than control of diastolic blood
      pressure. That this last point is also the case in major intervention trials
      suggests that normalization of systolic blood pressure may be intrinsically more
      difficult than normalization of diastolic blood pressure, possibly because of the
      difficulty of reversing the pathophysiological abnormalities responsible for the
      elevation of systolic blood pressure. This emphasizes the importance of research
      into new drugs or treatment types with greater efficacy in systolic hypertension.

PMID- 12187913
TI  - Proceedings of the 4th International Triticeae Symposium. Cordoba, Spain,
      September 2001.

PMID- 12187914
TI  - Abstracts of the Belgian Association for the Study of Cancer. January 26, 2002.

PMID- 12187915
TI  - Pravastatin and Aspirin.

PMID- 12187916
TI  - Omapatrilat.

PMID- 12187917
TI  - Adoption by same-sex parents.

PMID- 12187918
TI  - Robert Ozols receives important Cancer Research Award.

PMID- 12187919
TI  - [Speech pathology intervention for autistic children in Lebanon: status, needs
      and perspectives].

PMID- 12187920
TI  - [Progressive myoclonic epilepsy type Lafora].
AB  - Lafora's disease is a form of progressive myoclonic epilepsy characterized by
      seizures, myoclonus and dementia. We present the case of a 12-year-old girl who
      is complaining of epilepsy and myoclonic jerks starting a year ago, with
      deterioration of school performance, and abnormal EEG. The axillary skin biopsy
      showed PAS-positive inclusions in the cells of sweat glands, typical of Lafora's
      disease.

PMID- 12187921
TI  - To: Chandie Shaw PK, Vanderbrouke JP, Tjandra YL et al. (2002) Increased end
      stage diabetic nephropathy in Indo-Asian immigrants living in the Netherlands.
      Diabetologia 45: 337-341.

PMID- 12187922
TI  - Haptoglobin genotype and diabetic microangiopathies in Japanese diabetic
      patients.

PMID- 12187923
TI  - CD86 gene polymorphisms: no association with Type I diabetes among Finnish
      subjects.

PMID- 12187924
TI  - Autonomic neuropathy is associated with impaired pancreatic polypeptide and
      neuropeptide Y responses to insulin-induced hypoglycaemia in Type I diabetic
      patients.

PMID- 12187925
TI  - Beta-cell differentiation during human development does not rely on nestin
      positive precursors: implications for stem cell-derived replacement therapy.

PMID- 12187927
TI  - Bibliography of toxinology.

PMID- 12187926
TI  - Impaired glucose tolerance in pancreatic polypeptide-overexpressing mice.

PMID- 12187928
TI  - Amelioration of relapsing polychondritis in a child treated with oral collagen.
AB  - Relapsing polychondritis (RP) is a disease characterized by inflammation and the
      destruction of cartilage. The detection of antibodies to native type II collagen
      (CII) in the sera of some patients with relapsing polychondritis suggests that
      autoimmunity to this cartilage specific protein plays a role in the pathogenesis
      of the disease. RP is so rare that controlled therapeutic trials have not been
      carried out. We describe herein a child with RP who had amelioration of symptoms
      and a deviation in the cellular immune response to CII after being treated with
      daily oral CII as a toleragen.

PMID- 12187930
TI  - Nurses should be included in decisions regarding the purchase and use of venous
      access devices.

PMID- 12187931
TI  - Level of sedation may influence effect of virtual reality glasses during
      distraction therapy.

PMID- 12187932
TI  - From the United States to southern Ireland: translating the role of oncology
      advanced practice nurse.

PMID- 12187929
TI  - Dietary lipids alter the effect of steroids on the uptake of lipids following
      intestinal resection in rats.
AB  - Steroids alter the transport function of the intestine. This study was undertaken
      to assess the effect of glucocorticosteroids on lipid uptake in rats fed either a
      saturated (SFA) or a polyunsaturated fatty acid (PUFA) diet. Sprague-Dawley rats
      underwent transection or 50% resection of the small intestine. The steroids had
      no effect on the uptake of lipids. However, resection decreased the jejunal
      uptake of palmitic acid in animals fed SFA and increased the jejunal uptake of
      palmitic and linoleic acids in those fed PUFA. In animals undergoing intestinal
      resection, fed SFA, and given control vehicle, there was a reduction in jejunal
      proglucagon mRNA expression as compared to those fed chow or PUFA. Ornithine
      decarboxylase (ODC) mRNA expression in the jejunum of resected animals was
      reduced. In summary, dietary lipids modify the uptake of lipids in resected
      animals and ODC and proglucagon may be involved in this adaptive response.

PMID- 12187933
TI  - Respiratory distress in a patient with multiple myeloma.

PMID- 12187934
TI  - Vascular effects of GI262570X (PPAR-gamma agonist) in the brown adipose tissue of
      Han Wistar rats: a review of 1-month, 13-week, 27-week and 2-year oral toxicity
      studies.
AB  - We describe and discuss microscopic findings in the brown adipose tissue (BAT)
      blood vessels of Han Wistar rats treated with GI262570X, a peroxisome
      proliferator-activated receptor-gamma agonist (PPAR-gamma agonist) by oral gavage
      for 28 days, 13 weeks, 27 weeks, and 2 years. Review of these studies revealed a
      consistent vascular change, consisting of multifocal fatty infiltration in the
      BAT of treated rats. A similar vascular change was not seen in other vessels or
      organs. Microscopically, fatty infiltration was characterized primarily by round,
      clear vacuoles within the tunica media and/or tunica adventitia of small and
      medium-sized arteries and arterioles. Occasionally, these vacuoles had
      peripherally located nuclei and morphologically resembled adipocytes, suggesting
      a well-characterized PPAR effect (ie, differentiation of stem cells or
      preadipocytes into mature adipocytes). However, administration of GI262570X up to
      2 years failed to induce more severe or progressive lesions in the blood vessels
      of rat BAT and, in particular, did not result in induction of any atherosclerotic
      like lesions or foam cell infiltration. At the longer exposure, there was an
      apparent reduction of severity and/or incidence, indicating a possible adaptive
      response. These results suggest that the possibility of generating
      atherosclerotic-like lesions through prolonged treatment of GI262570X (PPAR-gamma
      agonist) is highly unlikely in rats.

PMID- 12187935
TI  - Systemic vascular disease in male B6C3F1 mice exposed to particulate matter by
      inhalation: studies conducted by the National Toxicology Program.
AB  - Epidemiological studies suggest an association between ambient particulate matter
      and cardiopulmonary diseases in humans. The mechanisms underlying these health
      effects are poorly understood. To better understand the potential relationship
      between particulate-matter-induced inflammation and vascular disease, a 2-phase
      retrospective study was conducted. Phase one included the review of heart, lung,
      and kidney tissues from high-dose and control male B6C3F1 mice exposed by
      inhalation to 9 particulate compounds for a 2-year period. The results showed
      that high-dose males developed significantly increased incidences of coronary and
      renal arteritis over controls in 2 of the 9 studies (indium phosphide and cobalt
      sulfate heptahydrate), while marginal increases in arteritis incidence was
      detected in 2 additional studies (vanadium pentoxide and gallium arsenide). In
      contrast, arteritis of the muscular arteries of the lung was not observed.
      Morphological features of arteritis in these studies included an influx of mixed
      inflammatory cells including neutrophils, lymphocytes, and macrophages. Partial
      and complete effacement of the normal vascular wall architecture, often with
      extension of the inflammatory process into the periarterial connective tissue,
      was observed. Phase 2 evaluated the heart, lung, kidney, and mesentery of male
      and female B6C3F1 mice from the 90-day studies of the 4 compounds demonstrating
      arteritis after a 2-year period. The results showed arteritis did not develop in
      the 90-day studies, suggesting that long-term chronic exposure to lower-dose
      metallic particulate matter may be necessary to induce or exacerbate arteritis.

PMID- 12187936
TI  - Application of cDNA microarray technology to in vitro toxicology and the
      selection of genes for a real-time RT-PCR-based screen for oxidative stress in
      Hep-G2 cells.
AB  - Large-scale analysis of gene expression using cDNA microarrays promises the rapid
      detection of the mode of toxicity for drugs and other chemicals. cDNA microarrays
      were used to examine chemically induced alterations of gene expression in HepG2
      cells exposed to a diverse group of toxicants at an equitoxic exposure
      concentration. The treatments were ouabain (43 microM), lauryl sulfate (260
      microM), dimethylsulfoxide (1.28 M), cycloheximide (62.5 microM), tolbutamide
      (12.8 mM), sodium fluoride (3 mM), diethyl maleate (1.25 mM), buthionine
      sulfoximine (30 mM), potassium bromate (2.5 mM), sodium selenite (30 microM),
      alloxan (130 mM), adriamycin (40 microM), hydrogen peroxide (4 mM), and heat
      stress (45 degrees C x 30 minutes). Patterns of gene expression were correlated
      with morphologic and biochemical indicators of toxicity. Gene expression
      responses were characteristically different for each treatment. Patterns of
      expression were consistent with cell cycle arrest, DNA damage, diminished protein
      synthesis, and oxidative stress. Based upon these results, we concluded that gene
      expression changes provide a useful indicator of oxidative stress, as assessed by
      the GSH:GSSG ratio. Under the conditions of this cell culture test system,
      oxidative stress upregulated 5 genes, HMOX1, p21(waf1/cip1), GCLM, GR, TXNR1
      while downregulating CYP1A1 and TOPO2A. Primers and probes for these genes were
      incorporated into the design of a 7-gene plate for RT-PCR. The plate design
      permitted statistical analysis and allowed clear discrimination between chemicals
      inducing oxidative vs nonoxidative stress. A simple oxidative stress score (0-1),
      based on the responses by the 7 genes (including p-value) on the RT-PCR plate,
      was correlated with the GSH:GSSG ratio using linear regression and ranking
      (Pearson product) procedures. These analyses yielded correlation coefficients of
      0.74 and 0.87, respectively, for the treatments tested (when 1 outlier was
      excluded), indicating a good correlation between the biochemical and
      transcriptional measures of oxidative stress. We conclude that it is essential to
      measure the mechanism of interest directly in the test system being used when
      assessing gene expression as a tool for toxicology. Tables 1-15, referenced in
      this paper, are not printed in this issue of Toxicologic Pathology. They are
      available as downloadable text files at
      http://taylorandfrancis.metapress.com/openurl.asp?genre=journal&issn=0192-6233.
      To access them, click on the issue link for 30(4), then select this article. A
      download option appears at the bottom of this abstract. In order to access the
      full article online, you must either have an individual subscription or a member
      subscription accessed through www.toxpath.org.

PMID- 12187937
TI  - Correlation of simultaneous differential gene expression in the blood and heart
      with known mechanisms of adriamycin-induced cardiomyopathy in the rat.
AB  - As the genomes of mammalian species become sequenced and gene functions are
      ascribed, the use of differential gene expression (DGE) to evaluate organ
      function will become common in the experimental evaluation of new drug therapies.
      The ability to translate this technology into useful information for human
      exposures depends on tissue sampling that is impractical or generally not
      possible in man. The possibility that the DGE of nucleated cells, reticulocytes,
      or platelets in blood may present the necessary link with target organ toxicity
      provides an opportunity to correlate preclinical with clinical outcomes.
      Adriamycin is highly effective alone and more frequently in combination with
      other chemotherapeutic agents in the treatment of a variety of susceptible
      malignancies. Adriamycin-induced cardiomyopathy was examined as an endpoint to
      measure the utility of DOE on whole blood as a predictor of cardiac toxicity.
      Statistically significant gene changes were observed between relevant blood and
      cardiac gene profiles that corroborated the accepted mechanisms of toxicity
      (oxidative stress, effects on carnitine transport, DNA intercalation). There
      were, however, clear indications that other target organs (bone marrow and
      intestinal tract) were affected. The divergent expression of some genes between
      the blood and the heart on day 7 may also indicate the timing and mechanism of
      development of the cardiomyopathy and confirm current therapeutic approaches for
      its prevention. The data demonstrate that whole blood gene expression
      particularly in relation to oxidative stress, in conjunction with standard
      hematology and clinical chemistry, may be useful in monitoring and predicting
      cardiac damage secondary to adriamycin administration. Appendices A & B,
      referenced in this paper, are not printed in this issue of Toxicologic Pathology.
      They are available as downloadable text files at
      http://taylorandfrancis.metapress.com/openurl.asp?genre=journal&issn=0192-6233.
      To access them, click on the issue link for 30(4), then select this article. A
      download option appears at the bottom of this abstract. In order to access the
      full article online, you must either have an individual subscription or a member
      subscription accessed through www.toxpath.org.

PMID- 12187938
TI  - Methapyrilene toxicity: anchorage of pathologic observations to gene expression
      alterations.
AB  - Methapyrilene (MP) exposure of animals can result in an array of adverse
      pathological responses including hepatotoxicity. This study investigates gene
      expression and histopathological alterations in response to MP treatment in order
      to 1) utilize computational approaches to classify samples derived from livers of
      MP treated rats based on severity of toxicity incurred in the corresponding
      tissue, 2) to phenotypically anchor gene expression pattems, and 3) to gain
      insight into mechanism(s) of methapyrilene hepatotoxicity. Large-scale
      differential gene expression levels associated with the exposure of male Sprague
      Dawley rats to the rodent hepatic carcinogen MP for 1, 3, or 7 days after daily
      dosage with 10 or 100 mg/kg/day were monitored. Hierarchical clustering and
      principal component analysis were successful in classifying samples in agreement
      with microscopic observations and revealed low-dose effects that were not
      observed histopathologically. Data from cDNA microarray analysis corroborated
      observed histopathological alterations such as hepatocellular necrosis, bile duct
      hyperplasia, microvesicular vacuolization, and portal inflammation observed in
      the livers of MP exposed rats and provided insight into the role of specific
      genes in the studied toxicological processes.

PMID- 12187939
TI  - Endocardial myxomatous change in Harlan Sprague-Dawley rats (Hsd:S-D) and CD-1
      mice: its microscopic resemblance to drug-induced valvulopathy in humans.
AB  - A full assessment of all heart valves in rats and mice is often impractical and
      is usually not performed in routine toxicity studies, largely due to an
      inevitable inconsistency of histological sampling. The majority of reported heart
      valve changes involve the examination of a single, semirandom section through the
      heart and the valvulopathy occurring with age or induced by xenobiotics may have
      been generally underestimated in mice and rats. Here we describe the incidence
      and microscopic features of endocardial myxomatous change (EMC) in Hsd:S-D rats
      and CD-1 mice. EMC was common and widespread in both CD-1 mice and Hsd:S-D rats
      (188 of 220 rats and 96 of 215 mice were affected by EMC). Microscopically, EMC
      consisted of focal or segmental thickening of valves, primarily due to the
      presence of fibromyxoid tissue in the subendocardium. Occasionally, fibrin or
      thrombi deposits and collection of neutrophils or mononuclear cells were
      observed. These microscopic features were similar to those seen in valvular
      disease in humans induced by fenfluramine-phentermine (fen-phen), ergot alkaloids
      (ergotamine, methysergide), and carcinoid syndrome. The mitral valve in rats and
      pulmonary valve in mice were most frequently affected. An association between
      murine progressive cardiomyopathy (MPC) and EMC was noted only in rats,
      suggesting that there may be a possible relationship between MPC and EMC.
      However, additional research is needed to confirm a relationship between EMC and
      MPC in rats and/or mice.

PMID- 12187940
TI  - Pheochromocytomas and ganglioneuromas in the aging rats: morphological and
      immunohistochemical characterization.
AB  - We investigated, morphologically and immunohistochemically, 74 medullary adrenal
      tumors, including 64 pheochromocytomas (14 malignant and 50 benign), 9
      ganglioneuromas, and 1 malignant schwannoma. The tumors were detected in 2-year
      old Wistar and Sprague-Dawley rats from carcinogenicity studies. Morphologically,
      benign pheochromocytomas were characterized by monomorphic, small, basophilic
      cells with almost absence of mitoses. Malignant pheochromocytomas presented a low
      grade of pleomorphism, higher rate of mitoses, necrosis, infiltrative growth and
      in 1 case metastases in the lung. Ganglioneuromas were characterized by ganglion
      and neuron-like cells embedded in an eosinophilic matrix containing neurites,
      Schwann cells, and scant fibrovascular elements. All pheochromocytomas were
      strongly immunoreactive for tyrosine hydroxylase (TH), the rate-limiting enzyme
      in catecholamine synthesis. Subpopulations of chromaffin cells expressed
      chromogranin A (CGA) positivity. Matrix and Schwann cells were positive for S-100
      and for glial fibrillary acidic protein (GFAP). In focal areas of the tumors,
      ganglion cells and axons were positive for neurofilament proteins (NFP) and
      synaptophysin. Ganglion cells exhibited peripherin and beta-tubulin.
      Proliferative activity of the tumors was assessed by immunostaining the
      endogenous cell proliferation associated-antigen Ki-67 and the proliferating cell
      nuclear antigen (PCNA). As expected, cell proliferation indices were much higher
      in malignant pheochromocytomas than in benign, yet ganglioneuromas remained
      immunonegative. Considering that Ki-67 antigen is more specific for cell
      proliferation, it should be regarded as marker of choice for supporting the
      differential diagnosis between benign and malignant pheochromocytomas.

PMID- 12187941
TI  - Skeletal myopathy in transgenic mice carrying human prototype c-Ha-ras gene.
AB  - Skeletal myopathy was found in almost all-transgenic mice carrying the human
      prototype c-Ha-ras gene (rasH2 mouse). Microscopically, variation of the muscle
      fiber size, centrally placed nuclei, regenerating fibers, and interstitial
      fibrosis were evident; hyalinization and necrosis were sometimes observed in the
      skeletal muscle (femoralis and pectoralis) of the rasH2 mice. Inflammatory
      changes in the skeletal muscle or abnormality of adjacent peripheral nerve were
      not observed. The features were essentially similar to those of muscular
      dystrophy. Although the severity was relatively mild compared to 34-week-old
      rasH2 mice, the skeletal myopathy was also observed in younger male (10 weeks of
      age) rasH2 mice. In nontransgenic littermates, skeletal myopathy was not
      observed. The mRNA of human c-Ha-ras product was detected in femoral muscle from
      the rasH2 mice by RT-PCR. In conclusion, these data suggest that skeletal
      myopathy is occurring in almost all rasH2 mice. Integration of c-Ha-ras gene is
      thought to be crucial to pathogenesis of skeletal myopathy in the rasH2 mice.
      Further characterization of the muscular lesion and its pathogenesis are needed
      to explore the possibility of rasH2 mouse becoming a new model for muscular
      dystrophy.

PMID- 12187942
TI  - Recommended approaches for the evaluation of testicular and epididymal toxicity.

PMID- 12187943
TI  - "Have you seen this?" peliosis hepatis.
AB  - Peliosis hepatis, characterized by the presence of blood-filled spaces within
      hepatic parenchyma, developed in C57Bl mice implanted subcutaneously with
      melanoma cells 23 days previously. The peliosis was associated with dilated
      hepatic sinusoids that were lined by prominent, proliferating endothelial cells.
      The development of peliosis hepatis was completely abrogated when melanoma growth
      was inhibited by administration of dexamethasone. These features support the
      concept that peliosis hepatis can be induced by a circulating tumor-derived
      endothelial growth factor such as vascular endothelial growth factor.

PMID- 12187944
TI  - Fixation of testes and eyes using a modified Davidson's fluid: comparison with
      Bouin's fluid and conventional Davidson's fluid.
AB  - Most recent revisions of regulatory guidelines for testing effects of chemicals
      on reproduction recommend Bouin's fluid (BF) or a "comparable fixative" instead
      of formalin to preserve the morphologic detail of testes for histopathological
      evaluation. However, picric acid in BF is a health and safety hazard, as well as
      a laboratory waste disposal problem. Furthermore, use of BF is labor intensive,
      requiring multiple alcohol rinses to remove picric acid for optimum preservation
      and immunohistochemical (IHC) detection of testicular antigens that may
      potentially be used to identify and quantify cells and functional proteins with
      critical roles in spermatogenesis. Recently a modified Davidson's fluid (mDF) has
      been reported as an altemative to BF to fix testes for routine histopathological
      examination. This study compared the overall histomorphologic clarity and the
      immuno- and histochemical staining of testicular specimens fixed in BF and mDF.
      Additionally, because conventional Davidson's fixative (DF) is used routinely for
      optimum fixation of eyes, preservation of ocular histomorphology by DF and mDF
      was compared. mDF resulted in noticeably less shrinkage of the seminiferous
      tubules and superior overall morphologic detail compared to BF. Unlike DF, the
      mDF also supported excellent staining of acrosomes with periodic acid-Schiff
      (PAS) reagent when staging of spermatogenesis was required. IHC detection of
      androgen receptor and PCNA (to directly and indirectly identify Sertoli cells) as
      well as protein gene product 9.5 (to label spermatogonia) was Superior in mDF
      compared to BF-fixed specimens. For histopathological examination of the eye,
      apposition and preservation of rods and cones, and nuclear layers of the retina
      were slightly inferior with mDF compared to DF. This paper has demonstrated that
      mDF provides comparable, and in many respects superior preservation of the testes
      to that of BF, both for IHC staining and for detailed histopathological
      examination. It also provides an acceptable fixative for eyes, although the
      quality of cellular preservation is inferior to that of DF.

PMID- 12187945
TI  - Committee on Mutagenicity of Chemicals in Food, Consumer Products and the
      Environment ILSI/HESI research programme on alternative cancer models: results of
      Syrian hamster embryo cell transformation assay. International Life Sciences
      Institute/Health and Environmental Science Institute.

PMID- 12187946
TI  - Response to Syrian Hamster Embryo Assay Working Group letter to the editor
      Toxicologic Pathology 30(2):292-293, 2002.

PMID- 12187948
TI  - [Long-term results after surgical treatment of pressure sores].
AB  - Thirty-one patients were operated on because of pressure sores. Twenty-five of
      these were investigated by means of an enquete. Twenty-two patients replied. In 9
      of 22 patients recurrence of pressure sores took place during the observation
      period, the mean observation time being 35 months. It is concluded that operative
      treatment of pressure sores, with the methods employed here can be recommended
      when the conservative treatment is protracted, or the conservative treatment does
      not result in improvement, provided that the patient is fully aware that
      consistent relief of pressure is necessary in the postoperative period and the
      general condition of the patient permits this. Special attention is necessary in
      patients with repeated recurrences of pressure sores, to ensure that the
      aforementioned conditions are fulfilled, before surgical treatment. The treatment
      of repeated recurrences of pressure sores involves many days of hospitalisation,
      and therefore very high costs.

PMID- 12187947
TI  - Microsatellites indicate a high frequency of multiple paternity in Apodemus
      (Rodentia).
AB  - Microsatellites were employed to estimate frequency of multiple paternity litters
      of two species of mice (genus Apodemus): striped field mouse (A. agrarius), and
      wood mouse (A. sylvaticus). Ten pregnant females of A. agrarius and six of A.
      sylvaticus were collected from natural populations in the northern Ukraine and
      analysed with 11 and nine microsatellite loci, respectively. Multiple paternity
      was indicated in eight of 10 litters in A. agrarius and in three of six litters
      in A. sylvaticus. Multiple paternity was documented at several loci (ranging from
      two to 10). In two cases (A. agrarius), three males were estimated to have
      fathered the litter.

PMID- 12187949
TI  - One year later: public health and safety: where we go from here, and what you can
      do.

PMID- 12187950
TI  - The perils of buying your own policy.

PMID- 12187951
TI  - Heartburn: picking the right remedy.

PMID- 12187952
TI  - Public access to defibrillators.

PMID- 12187954
TI  - Effect of hyperosmolar mannitol on convection-enhanced delivery into the rat
      brain stem.
AB  - INTRODUCTION: Convection-enhanced delivery (CED) can safely achieve high local
      infusate concentrations within the rat brain stem with predictable distribution
      volumes. The authors investigated the effects of co-infusion or systemic
      administration of hyperosmolar mannitol on distribution parameters for infusions
      into the rat brain stem. METHODS: Fifteen rats underwent stereotactic cannula
      placement into the pontine nucleus oralis (PnO) followed by infusions at a
      constant rate to a total volume of 1 microl. Five rats underwent infusion of
      fluorescein isothiocyanate (FITC)-dextran diluted in 20% mannitol. Five rats
      received an intraperitoneal injection of 20% mannitol 10 min prior to infusion of
      FITC-dextran diluted in isotonic saline. As a control group, 5 rats underwent
      infusion of FITC-dextran diluted in isotonic saline without mannitol
      administration. Serial brain sections were imaged using confocal microscopy with
      ultraviolet illumination, and distribution volume (Vd) was calculated by computer
      image analysis. Histologic analysis was performed on adjacent sections. RESULTS:
      Volumes of distribution were not significantly increased by co-infusion of
      mannitol directly into the brain stem or by systemic mannitol administration
      compared to infusion without mannitol. Similarly, mannitol administration by
      either means failed to significantly alter maximal cross-sectional area or cranio
      caudal extent of fluorescence. No animal demonstrated a postoperative
      neurological deficit or histologic evidence of tissue disruption. CONCLUSIONS:
      Neither systemic administration nor co-infusion of hyperosmolar mannitol
      significantly affects distribution parameters for CED infusions into the rat
      brain stem.

PMID- 12187955
TI  - Thymic carcinoma with brain metastasis mimicking meningioma.
AB  - Thymic carcinoma is a rare malignancy, which differs from thymoma in that it
      displays histopathologically malignant features, extensive local invasion, and a
      substantial potential for metastasis, predominantly to the liver and kidney and
      rarely to the central nervous system. Most of cerebral metastases are the
      intraaxial tumor, whereas extraaxial masses mimicking meningioma are extremely
      rare. A 32-year-old woman who had been treated for thymic carcinoma with multiple
      bone metastasis including spine and ribs was referred to the neurosurgery
      department with a diagnosis of right temporal extraaxial mass. Magnetic resonance
      imaging (MRI) revealed an extraaxial tumor with hemorrhage along the medial
      margin of tumor. A craniotomy was performed to remove the mass that was located
      extraaxially. Histopathological and immunohistochemical examination revealed
      undifferentiated thymic carcinoma with neuroendocrine differentiation. The
      patient recovered from the preoperative deficits, and local irradiation of 50 Gy
      was performed. This paper will examine briefly the radiolographic and pathologic
      characteristics of this unusual lesion. Although extraaxial thymic carcinomas are
      rare, they should be considered in the radiographic differential diagnosis of
      dural-based lesions, especially for patients with history of thymic lesions.

PMID- 12187956
TI  - Immunohistochemical markers for prognosis of anaplastic astrocytomas.
AB  - Among the entire spectrum of astrocytic neoplasms, just anaplastic astrocytoma
      (or grade III astrocytoma) appears to be a more enigmatic tumor entity with vague
      criteria for pathological diagnosis, unclear biological behavior and diverse
      clinical outcome. Attempts have been made to identify biological markers that
      would be useful in prediction of prognosis of anaplastic astrocytomas but the
      results obtained are controversial. In the present study, survival data on 63
      patients with anaplastic astrocytoma were studied to evaluate a possible
      association between clinical outcome and expression of some immunohistochemical
      variables. Both the progression-free (PFS) and overall (OS) survival times were
      significantly reduced for patients older than 45 years, for anaplastic
      astrocytomas containing multiple mitoses, for Ki-67 LI > 5%, for cyclin A LI > 4%
      and for PTEN-negative tumors. We found no differences in survival times in
      patients with or without p53 immunoreactivity and also in cases with different
      values of p16 and p27 immunostaining. Multivariate analysis revealed that risk of
      tumor progression and death is independently associated with tumors containing
      multiple mitoses and for PTEN-negative tumors. According to the data from the
      CART modeling, tumors were subdivided based on the three following subsets: (1)
      Anaplastic astrocytomas with solitary mitosis. (2) Anaplastic astrocytomas with
      multiple mitoses and PTEN positivity. (3) Anaplastic astrocytomas with multiple
      mitoses and PTEN negativity. Thus, the results obtained reveal the advantage of
      combined approach including evaluation of routine histological parameters and
      immunohistochemical variables for further clinical subdivision of anaplastic
      astrocytomas.

PMID- 12187958
TI  - Immunohistochemical markers for prognosis of oligodendroglial neoplasms.
AB  - Despite numerous previous studies, oligodendrogliomas continue to generate
      considerable controversy in the identification of prognostic factors, including
      single histopathological patterns, and grade of tumor malignancy. The prognostic
      significance of various pathological and immunohistochemical factors has been
      intensively examined but numerous studies have yielded conflicting results. In
      the present study, biopsy samples of 123 oligodendrogliomas were examined
      immunohistochemically to evaluate a possible association between expression of
      various tumor-associated antigens and clinical outcome. Both the progression-free
      and overall survival times were significantly reduced for high-grade tumors, for
      Ki-S1 labeling index (LI) > 10%, for p27 LI < 20% and for p18, p53, and vascular
      endothelial growth factor (VEGF)-positive tumors. For low-grade tumors survival
      rates were significantly reduced for p27 LI less than 20%, whereas high-grade
      oligodendrogliomas with Ki-S1 LI greater than 10%, and with p18 positivity
      revealed significantly shortened survival times. We found no differences in
      survival times in patients with or without p 14ARF, p21, mdm2, and pRb
      immunoreactivity. Multivariate analysis revealed that risk of oligodendroglioma
      progression is associated with high-grade tumors, with Ki-S1 LI > 10%, and with
      p27 LI < 20%; whereas risk of death is associated with high-grade tumors, with Ki
      S1 LI > 10%, and with p18 positivity. CART modeling process identified four final
      groups of oligodendroglioma patients: (1) thirty-nine patients with low-grade
      tumors and p27 LI > 20%; (2) twenty patients with low-grade tumors and p27 LI <
      20%; (3) thirty-four patients with high-grade tumors and Ki-S1 LI < 10%; and (4)
      thirty patients with high-grade tumors and Ki-S1 LI >10%. In summary, both the
      p27 and Ki-S1 scores were found to be the strong predictors of oligodendroglioma
      outcome together with the WHO tumor grade and they seem to be useful for
      assessing individual prognosis in routinely processed specimens.

PMID- 12187961
TI  - Application of solid-phase microextraction in the monitoring of priority
      pesticides in the Kalamas River (N.W. Greece).
AB  - A solid-phase microextraction (SPME) method was applied to an extended monitoring
      survey of priority pesticides for the European Union for a period of 12 months in
      water of the Kalamas River (Epirus region of northwestern Greece) in order to
      determine their concentrations and seasonal variations. Polydimethylsiloxane
      coated fiber (100 microm) was used. The samples were screened using gas
      chromatography with flame thermionic detection. Detection was confirmed by gas
      chromatographymass spectroscopy. The most frequently detected pesticides were
      some of the more commonly used herbicides, such as S-ethyl-N,N-di-n-propylthiol
      carbamate (EPTC), trifluralin, atrazine, deethylatrazine, terbuthylazine and
      alachlor, and insecticides, such as carbofuran, diazinon, disulfoton, parathion
      methyl, parathion ethyl, fenthion and ethion. Concentrations of individual
      compounds ranged from 0.020 to 0.3 microg/L. Greater pesticide concentrations
      occurred during the seasons of application. A comparison with a well-established
      solid-phase extraction (C18 disks) procedure was performed for samples of high
      season application (May-September) in order to confirm the effectiveness of the
      SPME technique. The results demonstrate the suitability of the SPME method for
      routine screening multiresidue analysis in natural waters.

PMID- 12187957
TI  - Immunohistochemical markers for prognosis of cerebral glioblastomas.
AB  - Glioblastoma is the commonest neuroectodermal tumor and the most malignant in the
      range of cerebral astrocytic gliomas. The prognostic utility of various
      biological markers for glioblastomas has been broadly tested but the results
      obtained are regarded as controversial. In the present study, 302 glioblastoma
      specimens were studied to evaluate a possible association between clinical
      outcome and expression of some immunohistochemical variables. Furthermore, tumors
      examined were subdivided on the three cytological subsets--small-cell (SGB),
      pleomorphic-cell (PGB) and gemistocytic (GGB). Immunohistochemical variables
      differed between various subsets: the number of p53-positive tumors was found to
      be prevailed among the PGB, whereas the number of tumors with EGFR and mdm2
      positivity was significantly greater in SGB. GGB contained significantly lowest
      mean proliferating cell nuclear antigen (PCNA) labeling index (LI), greater
      number of p21ras positive cases, and higher mean apoptotic index (AI). Survival
      time in patients with SGB, EGFR and mdm2-positivity and PCNA LI >40% was found to
      be significantly shorter, whereas presence of p21ras and AI >0.5% were associated
      with prolonged survival. Multivariate analysis revealed that survival time is
      associated with SGB, EGFR-positivity, and AI (p = 0.0023, p = 0.0035 and p =
      0.0029 respectively). We conclude that although some immunohistochemical
      variables were found to be significant for glioblastoma outcome, they appear to
      be closely related to biology of single cytological subsets. Furthermore, these
      variables exhibited no prognostic value when they were analyzed within each
      cytological subset separately. Therefore, the glioblastoma subdivision on three
      cytological subsets proposed by us is carrying some element of rationality but,
      undoubtedly, requires further prospective studies.

PMID- 12187959
TI  - Immunohistochemical markers for prognosis of ependymal neoplasms.
AB  - Intracranial ependymomas are the third most common primary brain tumor in
      children. Although clinical and histological criteria for ependymoma prognosis
      are recognized, studies have reported contradictory results. Prognostic
      significance based on immunohistochemistry of ependymomas has been reported in a
      few studies. One-hundred and twelve patients with intracranial ependymomas were
      examined retrospectively for immunoexpression of various tumor-associated
      antigens and apoptosis. The results demonstrated significant preponderance of
      expression of the tenascin, vascular endothelial growth factor protein (VEGF),
      epidermal growth factor (EGFR) and p53 protein in high-grade tumors. Also high
      grade ependymomas revealed more prominent labeling indices (LI) for proliferative
      marker Ki-S1 and apoptotic index (AI), and lower LI for cyclin-dependent kinase
      inhibitors p27/Kipl and pl4ARF. For low-grade ependymomas the progression-free
      survival time (PFS) was found to be significantly shorter for Ki-S1 LI > 5%, and
      for tenascin, VEGF and EGFR positivity. For high-grade ependymomas PFS was found
      to be significantly reduced for p27 LI < 20%, p14ARF LI < 10%, for p53
      positivity, and for AI < 1%. The CART modeling process exhibited five final
      groups of ependymoma patients (1) low-grade and tenascin-negative; (2) low-grade
      and tenascin-positive; (3) high-grade and p53-negative with p14 LI > 0%; (4) high
      grade with combination of either p53 positivity and p14 LI > 10% or p53
      negativity and p14 LI < 10%; (5) high-grade and p53-positive with pl4 LI < 10%.
      In summary, some immunohistochemical variables were found to be the strong
      predictors of ependymoma recurrence and they seem to be useful for assessing
      individual tumor prognosis in routinely processed biopsy specimens together with
      tumor grade. For histologically benign ependymomas immunohistochemical study
      should be focused on Ki-S1, tenascin, EGFR and VEGF evaluation, whereas p53
      expression and number of p27, p14 and ISEL-positive nuclei will be of value in
      determining PFS from high-grade ependymomas.

PMID- 12187960
TI  - Immunohistochemical markers for prognosis of average-risk pediatric
      medulloblastomas. The effect of apoptotic index, TrkC, and c-myc expression.
AB  - Medulloblastomas (MB) are the most common central nervous system malignancies in
      children. Numerous publications describe certain efforts to identify predictive
      value of various patterns of MB pathology and immunohistochemistry but received
      data appear to be controversial. In the present study, the apoptotic index (AI)
      and immunoexpression of TrkC, and c-myc proteins were investigated in biopsy
      samples from 68 MB with an average clinical risk to determine their prognostic
      utility in this tumor category. The number of cases with AI > 1.5% was
      significantly greater in the group of tumors in patients with recurrent MB and
      the mean AI was significantly higher in this group -4.7% vs. 1.1%. Furthermore,
      the number of tumors with AI > 1.5% was greater in the group of tumors in
      deceased patients and the mean Al was also higher in this group -4.6% vs. 1.2%.
      Immunoreactivity of the c-myc and TrkC did not show any differences between
      groups of patients with various clinical outcomes. A close association between Al
      as a continuous variable and the progression-free and overall survival was found.
      We found no any differences in survival times for c-myc and TrkC
      immunoreactivity. Multivariate revealed analysis that AI is a single significant
      prognostic factor for MB survival. Perhaps, investigations of c-myc and TrkC mRNA
      levels should be useful for clinical purposes, but in order to introduce these
      biomolecular markers in clinical protocols its distinct prognostic significance
      needs to be proved by prospective studies.

PMID- 12187962
TI  - Comparison of solid-phase extraction and solid-phase microextraction for
      carbofuran in water analyzed by high-performance liquid chromatography-photodiode
      array detection.
AB  - In this study a direct solid-phase microextraction (SPME) procedure has been
      developed for the determination of carbofuran in water. Experimental parameters
      such as selection of SPME coating, effect of temperature, effect of salt addition
      and solvent desorption were studied and optimized. Analytical parameters such as
      linearity, precision, detection and quantitation limits, and matrix effects for
      solid-phase extraction (SPE) and SPME methods were evaluated for comparison
      purposes with the aim of selecting the most appropriate depending on the
      detection capabilities required. SPE and SPME were followed by high-performance
      liquid chromatography with diode-array detection, using a 50 x 4.6 mm I.D. guard
      column and a 150 x 4.6 mm I.D. analytical column, both packed with C18 silica.
      Both methods can be applied to real samples and give the same results, but SPE
      allows the detection of lower carbofuran concentrations (0.06 microg/L) as
      compared to

PMID- 12187963
TI  - Rapid trace analysis of alachlor in water and vegetable samples.
AB  - The use of a rapid and specific (cross-reactivity<4%) enzyme-linked immunosorbent
      assay (ELISA) for the determination of alachlor residues in water and vegetable
      samples is addressed. The analytical method consists of a fast extraction
      procedure followed by an optimised ELISA. The detection limit was 0.44 microg l(
      1), with a linear range from 0.89 to 143.2 microg l(-1). For alachlor extraction
      from water samples, different solid-phase cartridges (C, Ph, C8 and C2) were
      assayed using MeOH as eluent. Extracts were diluted (1:4) with distilled water
      before ELISA. This procedure gave recoveries close to 100% with RSDs<14%. For
      vegetable samples, alachlor was extracted directly with MeOH and the extracts
      diluted 1:40 (v/v) with saline buffer prior to ELISA. The results obtained by the
      proposed procedure correlate well with the reference method (multiresidue
      extraction-GC-MS) for vegetable samples (r>0.85).

PMID- 12187964
TI  - Optimization of a derivatization-solid-phase microextraction method for the
      analysis of thirty phenolic pollutants in water samples.
AB  - Solid-phase microextraction (SPME) coupled to gas chromatography-mass
      spectrometry has been applied to the extraction of 30 phenol derivatives from
      water samples. Analytes were in situ acetylated and headspace solid-phase
      microextraction was performed. Different parameters affecting extraction
      efficiency were studied. Optimization of temperature, type of microextraction
      fiber and volume of sample has been done by means of a mixed-level categorical
      experimental design, which allows to study main effects and second order
      interactions. Five different fiber coatings were employed in this study; also,
      extraction temperature was studied at three levels. Both factors, fiber coating
      and extraction temperature, were important to achieve high sensitivity. Moreover,
      these parameters showed a significant interaction, which indicates the different
      kinetic behavior of the SPME process when different coatings are used. It was
      found that 75 microm carboxen-polydimethylsiloxane and 100 microm
      polydimethylsiloxane, yield the highest responses. The first one is specially
      appropriated for phenol, methylphenols and low chlorinated chlorophenols and the
      second one for highly chlorinated phenols. The two methods proposed in this study
      shown good linearity and precision. Practical applicability was demonstrated
      through the analysis of a real sewage water sample, contaminated with phenols.

PMID- 12187965
TI  - Universal screening method for the determination of US Environmental Protection
      Agency phenols at the lower ng l(-1) level in water samples by on-line solid
      phase extraction-high-performance liquid chromatography-atmospheric pressure
      chemical ionization mass spectrometry within a single run.
AB  - The applicability of a previously optimized method for the analysis of the US
      Environmental Protection Agency (EPA) regulations phenols, based on on-line solid
      phase extraction coupled to liquid chromatography with mass spectrometric (MS)
      detection in different matrix loaded water samples is demonstrated. The
      comprehensive optimization of the mobile phase conditions and their influence on
      the ionization process in atmospheric pressure ionization is described in detail.
      In particular, MS detection of the weakly acidic phenols such as phenol,
      monochlorinated phenols and methylated phenols requires the absence of acidic
      mobile phase modifiers and buffers. Thus lower retention times and slight peak
      broadening of the more acidic dinitrophenols are obtained if the entire range of
      EPA phenols is analyzed within a single chromatographic run. The figures of merit
      for the method were determined and the applicability to real water samples was
      investigated. Limits of detection for phenols ranging from 40 to 280 ng l(-1) and
      relative standard deviations below 8% in SCAN mode are obtained for all phenols
      if only 10-ml river water samples with low dissolved organic carbon (DOC 5 mg C
      l(-1) concentrations are preconcentrated. The method was used to detect 2
      nitrophenol and 4-nitrophenol in river water samples in the lower ng l(-1) range.
      The analysis of highly matrix-loaded samples (DOC 210 mg C l(-1)) requires a
      reduced enrichment volume resulting in decreased sensitivity. Still the method is
      capable of reaching excellent detection limits which demonstrates its excellent
      suitability for screening analysis.

PMID- 12187966
TI  - Development of a solid-phase microextraction method for the determination of
      short-ethoxy-chain nonylphenols and their brominated analogs in raw and treated
      water.
AB  - A direct solid-phase microextraction (SPME) procedure has been developed and
      applied for the simultaneous determination of nonylphenol, nonylphenol mono- and
      diethoxylates and their brominated derivatives in raw and treated water at low
      microg l(-1) concentrations. Several parameters affecting the SPME procedure,
      such as extraction mode (headspace or direct-SPME), selection of the SPME
      coating, extraction time, addition of organic modifiers such as methanol and
      temperature were optimized. The divinylbenzene-carboxen-polydimethylsiloxane
      fiber was the most appropriate one for the determination of nonylphenol
      ethoxylates (NPEOs) and bromononylphenol ethoxylates (BrNPEOs) by SPME-GC-MS. The
      optimized method was linear over the range studied (0.11-2.5 microg l(-1)) and
      showed good precision, with RSD values between 4 and 15% and detection limits
      ranging from 30 to 150 ng l(-1) depending on the compound. The SPME procedure was
      compared with a solid-phase extraction-GC-MS method (C18 cartridge) for the
      analysis of NPEO and BrNPEOs in water samples. There was good agreement between
      the results from both methods but the SPME procedure showed some advantages such
      as lower detection limits, a shorter analysis time and the avoidance of organic
      solvents. The optimized SPME method was applied to determine nonylphenol and
      brominated metabolites in raw and treated water of Barcelona (NE Spain).

PMID- 12187967
TI  - Non-covalent and semi-covalent molecularly imprinted polymers for selective on
      line solid-phase extraction of 4-nitrophenol from water samples.
AB  - Two molecularly imprinted polymers (MIPs) have been synthesised for the selective
      extraction of 4-nitrophenol (4-NP) from water samples. One polymer was
      synthesised via a non-covalent approach and the other via a semi-covalent
      approach. The selectivity of the polymers for 4-NP was evaluated when these
      polymers were applied in on-line solid-phase extraction (MISPE) coupled to
      reversed-phase HPLC. The MISPE conditions for both MIPs were optimised and a
      clean-up step was included to eliminate non-specific interactions. Differences
      between the two MIPs were observed with the non-covalent MIP being the more
      selective of the two, whereas the recoveries were slightly higher for the semi
      covalent MIP. The performance of the imprinted polymers in the MISPE of real
      water samples was also evaluated.

PMID- 12187968
TI  - Application of solid-phase microextraction combined with gas chromatography-mass
      spectrometry to the determination of butylated hydroxytoluene in bottled drinking
      water.
AB  - Butylated hydroxytoluene (BHT) is an antioxidant utilized as additive in foods
      and packaging plastic. Its presence in drinking water is possible if it is used
      as an antioxidant in the packaging plastic because it may migrate into the
      package's contents. A method for the determination of BHT in water by means of
      solid-phase microextraction and gas chromatography-mass spectrometry has been
      developed and evaluated with respect to the time of fiber exposure, limits of
      detection and quantitation, linearity and precision. Finally, the method was
      applied to evaluate the presence of this substance in samples of mineral and
      mineralized bottled drinking water, and it appeared to be present in seven out of
      a total of fifteen commercial brands.

PMID- 12187969
TI  - Solid-phase extraction for the simultaneous preconcentration of organic
      (selenocystine) and inorganic [Se(IV), Se(VI)] selenium in natural waters.
AB  - This paper describes the combined use of a new preconcentration method using the
      Amberlite IRA-743 resin and high-performance liquid chromatography coupled to
      inductively coupled plasma mass spectrometry to determine simultaneously
      inorganic and organic selenium species in aquatic systems. The developed
      enrichment procedure, whose accuracy has been checked by recovery tests, is
      suitable for selenium speciation at environmental levels of 10 ng (Se) l(-1). The
      method has been applied to mineral and freshwater samples.

PMID- 12187971
TI  - Rapid determination of butyltin species in water samples by multicapillary gas
      chromatography with atomic emission detection following headspace solid-phase
      microextraction.
AB  - A procedure for the rapid determination of mono-, di- and tributyltin in water
      samples is described. The analytes are simultaneously ethylated and concentrated
      on a solid-phase microextraction fibre placed in the headspace over the sample
      for 2 min. The ethylated species are then separated and selectively quantified in
      only 90 s using a multicapillary gas chromatography column combined with atomic
      emission detection. The influence of blank signals and sampling conditions on the
      sensitivity of the method is described. Detection limits of 1-5 ng/l and relative
      standard deviations of 6-10% at concentrations of 20 ng/l were obtained.

PMID- 12187970
TI  - Comparison of three different poly(dimethylsiloxane)-divinylbenzene fibres for
      the analysis of pesticide multiresidues in water samples: structure and
      efficiency.
AB  - Despite the continuing development of SPME (solid-phase microextraction) fibre
      coatings, their selection presents some difficulties for analysts in choosing the
      appropriate fibre for a certain application. There are two distinct types of SPME
      coatings available commercially. The most widely used are poly(dimethylsiloxane)
      (PDMS) and poly(acrylate) (PA). Supelco has developed new mixed phases consisting
      of porous polymer particles, either poly(divinylbenzene) (DVB) or Carboxen
      suspended in a matrix of PDMS or Carbowax for extracting analytes via adsorption.
      In addition to the nature of the extracting phase, the thickness of the polymeric
      film must be taken into account and, surprisingly, the construction of the fibres
      when apparently they bear the same coating, as it is the case of the three PDMS
      DVB fibres available. Other fibre structure properties not well explored were
      identified and must be taken into consideration. To elucidate their extraction
      efficiency, three PDMS-DVB fibres, namely 60 microm for HPLC use, 65 microm for
      GC use and 65 microm StableFlex for GC use, were compared with regard to the
      extraction of 36 compounds included in four pesticide groups. The first was
      particularly suited for the extraction of organophosphorus pesticides and
      triazines whereas the StableFlex exhibited advantages in the analysis of
      organochlorine pesticides and pyrethroids. An explanation for the extraction
      differences is suggested based on the different structure of the fibres.
      Detection limits in the range of 1-10 ng/l for organochlorine pesticides, 1-30
      ng/l for organophosphorus pesticides, 8-50 ng/l for triazines and 10-20 ng/l for
      pyrethroids were attained in a method using the 60 microm PDMS-DVB fibre. The
      fibre maintains its performance at well above 100 extractions with between-day
      precision below 10%.

PMID- 12187972
TI  - Chemically facilitated chromium(VI) transport throughout an anion-exchange
      membrane application to an optical sensor for chromium(VI) monitoring.
AB  - The Raipore R1030 membrane, an anion-exchange membrane containing ammonium groups
      as ionogenic groups, was evaluated as the interface of an optical sensor for
      Cr(VI), and the effect of chemical parameters affecting Cr(VI) transport were
      studied. Good transport features were obtained, demonstrating the suitability of
      the Raipore R1030 membrane for this application. Thus, an optical sensor for
      chromium(VI) monitoring in industrial process waters was developed. The sensor is
      based on the renewable reagent approach and uses the Raipore R1030 membrane as
      the interface between the sample and the sensor head, which contains 1,5
      diphenylcarbazide as spectrophotometric reagent for chromium. Chromium(VI)
      crosses the membrane and reacts with the reagent inside the sensor head,
      resulting in changes in the absorption of light. These changes are monitored in
      situ through a system of optical fibers. The sensor performance was tested by
      analysing samples from a waste water treatment plant for effluents from
      electroplating industries.

PMID- 12187974
TI  - Application of stir bar sorptive extraction to the determination of polycyclic
      aromatic hydrocarbons in aqueous samples.
AB  - The technique of stir bar sorptive extraction is used for the determination of
      polycyclic aromatic hydrocarbons (PAH) in aqueous samples. The PAHs are extracted
      with 10-mm stir bars (Gerstel Twister) coated with 0.5 mm polydimethylsiloxane
      and analyzed with a gas chromatography-mass spectrometry system. The influence of
      methanol and hyamine addition to the samples for preventing wall effects is
      investigated at 100 ng/l. The results indicate improved sensitivity using hyamine
      addition to the samples. The optimal extraction time was found to be between 3
      and 4 h. The reproducibility of the method, as determined by nine replicate
      measurements, is between 5 and 15% at 10 ng/l and between 3 and 9% at 50 ng/l.
      Carry-over, which was evaluated at 500 ng/l by desorbing the same Twister three
      times, seems to be negligible for most of the compounds. In worst cases, carry
      over of up to 7% was found for indeno[1,2,3]pyrene, dibenz[a,h]anthracene, and
      benzo[g,h,i]perylene. The technique shows excellent linearities for 5 point
      calibrations. Detection limits are between 0.1 and 2 ng/l.

PMID- 12187973
TI  - Determination of esters in dry and sweet white wines by headspace solid-phase
      microextraction and gas chromatography.
AB  - Headspace solid-phase microextraction (HS-SPME) was studied for the high
      resolution gas chromatographic (HRGC) analysis of esters in wines. Five different
      SPME fibers were tested and the influence of different factors such as
      temperature and time of desorption, extraction time, extraction technique,
      stirring, sample and vial volume, sugar and ethanol content were studied and
      optimised using model solutions. The proposed HS-SPME-GC method is an appropriate
      technique for the quantitative analysis of esters in dry and sweet white wines.

PMID- 12187975
TI  - Liquid-liquid-liquid microextraction of aromatic amines from water samples
      combined with high-performance liquid chromatography.
AB  - A simple preconcentration and clean-up liquid-liquid-liquid microextraction of
      aromatic amines is described in this paper. The compounds were extracted from 2.0
      ml aqueous samples (donor phase) into an organic phase, layered on the donor
      phase, and then back extracted to a microdrop of aqueous receiving phase,
      suspended in the organic phase. After extraction, the microdrop was injected into
      the HPLC system directly for analysis. Optimal conditions of the extraction were
      donor phase (a1): 2 ml of water sample adjusted to pH 13 with NaOH-NaCl; organic
      phase (o), 150 microl ethyl acetate; and receiving phase (a2) of 2 microl aqueous
      solution at pH 2.1. The a1-->o extraction time was 15 min and for o-->a2, 30 s.
      18-Crown-6 ether, which can complex with amine, was added to the aqueous
      receiving phase to improve the extraction performance. Enrichment factors ranged
      from 218 (for 4-nitroaniline) to 378 (for 4-chloro-2-aniline). The calibration
      curve for these anilines was linear within the range 2.5 ng/ml-2.5 microg/ml
      (r2=0.998). Detection limits ranged from 0.85 to 1.80 ng/mi (at S/N=3). This
      procedure can be a selective preconcentration method for aromatic amines present
      in water samples.

PMID- 12187976
TI  - Analysis of aromatic amines in water samples by liquid-liquid-liquid
      microextraction with hollow fibers and high-performance liquid chromatography.
AB  - Liquid-liquid-liquid microextraction (LLLME) with hollow fibers in high
      performance liquid chromatography (HPLC) has been applied as a rapid and
      sensitive quantitative method for the detection of four aromatic amines (3
      nitroaniline, 4-chloroaniline, 4-bromoaniline and 3,4-dichloroaniline) in
      environmental water samples. The preconcentration procedure was induced by the pH
      difference inside and outside the hollow fiber. The target compounds were
      extracted from 4-ml aqueous sample (donor solution, pH approximately 13) through
      a microfilm of organic solvent (di-n-hexyl ether), immobilized in the pores of a
      hollow fiber (1.5 cm length x 0.6 mm I.D.), and finally into 4 microl of acid
      acceptor solution inside the fiber. After a prescribed period of time, the
      acceptor solution inside the fiber was withdrawn into the microsyringe and
      directly injected into the HPLC system for analysis. Factors relevant to the
      extraction procedure were studied. Up to 500-fold enrichment of analytes could be
      obtained under the optimized conditions (donor solution: 0.1 M sodium hydroxide
      solution with 20% sodium chloride and 2% acetone; organic phase: di-n-hexyl
      ether; acceptor solution: 0.5 M hydrochloric acid and 500 mM 18-crown-6 ether;
      extraction time of 30 min; stirring at 1,000 rev./min). The procedure also served
      as a sample clean-up step. The influence of humic acid on the extraction
      efficiency was also investigated, and more than 85% relative recoveries of the
      analytes at two different concentrations (20 and 100 microg/l) were achieved at
      various concentration of humic acid. This technique is a low cost, simple and
      fast approach to the analysis of polar compounds in aqueous samples.

PMID- 12187977
TI  - Determination of volatile alkyl sulfides in wastewater by headspace solid-phase
      microextraction followed by gas chromatography-mass spectrometry.
AB  - An analytical procedure based on headspace solid-phase microextraction (SPME)
      followed by gas chromatography coupled to mass spectrometry in the electron
      impact mode has been developed for the determination of low-molecular-mass
      sulfides and disulfides in wastewater. Parameters affecting to the extraction of
      these volatile alkyl sulfides (VASs) with the SPME, such as the extraction
      temperature, sample volume, pH and the NaCl addition to the matrix, have been
      optimised using a polydimethylsiloxane-Carboxen fibre. The linear dynamic range
      was close to three orders of magnitude for all the studied compounds. Detection
      limits of 4 ng l(-1) for dimethyl sulfide, 0.7 ng l(-1) for ethylmethyl sulfide,
      5 ng l(-1) for diethyl sulfide and 1 ng l(-1) for dimethyl disulfide were
      achieved, with a relative standard deviation between 4 and 6%. The developed
      analytical methodology was applied to determine those VASs in different
      wastewaters.

PMID- 12187978
TI  - Optimization of headspace solid-phase microextraction by means of an experimental
      design for the determination of methyl tert.-butyl ether in water by gas
      chromatography-flame ionization detection.
AB  - A procedure for determination of methyl tert.-butyl ether (MTBE) in water by
      headspace solid-phase microextraction (HS-SPME) has been developed. The analysis
      was carried out by gas chromatography with flame ionization detection. The
      extraction procedure, using a 65-microm poly(dimethylsiloxane)-divinylbenzene
      SPME fiber, was optimized following experimental design. A fractional factorial
      design for screening and a central composite design for optimizing the
      significant variables were applied. Extraction temperature and sodium chloride
      concentration were significant variables, and 20 degrees C and 300 g/l were,
      respectively chosen for the best extraction response. With these conditions, an
      extraction time of 5 min was sufficient to extract MTBE. The calibration linear
      range for MTBE was 5-500 microg/l and the detection limit 0.45 microg/l. The
      relative standard deviation, for seven replicates of 250 microg/l MTBE in water,
      was 6.3%.

PMID- 12187979
TI  - Determination of toxic compounds in paper-recycling process waters by gas
      chromatography-mass spectrometry and liquid chromatography-mass spectrometry.
AB  - Three analytical methods were developed for the determination of toxic compounds
      in recirculating waters of a paper-recycling industry. Three main groups of
      compounds were considered: (i) wood extractives originated from the raw material;
      (ii) biocides added during the production process and (iii) surfactants and other
      adjuvants present in the formulates of these biocides. Wood extractives
      considered in this study included fatty and resin acids. They were analysed by
      liquid-liquid extraction using methyl tert.-butyl ether, followed by gas
      chromatography-mass spectrometry for previous formation of the respective
      trimethylsilyl esters. Water samples were also extracted with Oasis HLB
      (copolymer [poly(divinylbenzene-co-N-vinylpyrrolidone]) solid-phase extraction
      cartridges of 60 mg and analysed by liquid chromatography-electrospray mass
      spectrometry for the determination of additives and biocides. Using these two
      approaches levels up to 15 mg/l for total resin and fatty acids, 5 mg/l for
      alkylbenzene sulfonates and 2-(thiocyanomethylthio)benzotiazol, 100 microg/l for
      bisphenol A and 2,2-dibromo-3-nitrilepropionamide, and 300 microg/l for
      nonylphenol ethoxycarboxylate were detected in process waters at different
      production treatment stages. These levels are of relevance since poor water
      quality affects the paper-recycling process, the primary water treatment process
      and eventually, the environmental water quality.

PMID- 12187980
TI  - Membrane-assisted solvent extraction of triazines and other semi-volatile
      contaminants directly coupled to large-volume injection-gas chromatography-mass
      spectrometric detection.
AB  - A simple device was developed for in-vial liquid-liquid extraction using a
      polymer membrane (nonporous polypropylene) to separate an aqueous sample from an
      organic extractant. The membrane consisted of tubing with an internal diameter of
      6 mm and a wall thickness of 0.05 mm, which was heat-sealed at the lower end and
      filled with 500 microl hexane. This membrane bag was incorporated into a
      conventional 20 ml headspace vial suitable for a multi-purpose sampler (MPS 2,
      Gerstel, Mulheim, Germany) directly interfaced to a gas chromatograph with a mass
      selective detector. The sampler enabled the extraction vial to be mixed at a
      defined temperature with subsequent large-volume injection of the organic extract
      taken from the membrane bag. The method was evaluated using several triazines,
      2,4-dichloroaniline, alpha-hexachlorocyclohexane and phenanthrene as model
      compounds. Extraction parameters such as temperature, agitation speed, and
      extraction time were optimised. Recoveries of 60-90% were achieved after 30 min
      extraction. By increasing the injection volume to 100 microl, detection limits of
      1-10 ng/l were determined.

PMID- 12187981
TI  - Optimisation of a solid-phase microextraction method for synthetic musk compounds
      in water.
AB  - A solid-phase microextraction method (SPME) for determining trace levels of
      synthetic musk fragrances in residual waters has been developed. Six polycyclic
      musks (cashmeran, phantolide, celestolide, traseolide, galaxolide and tonalide),
      and a macrocyclic musk (ambrettolide) have been analysed. A detailed study of the
      different parameters affecting the extraction process is presented. The main
      important factors affecting the microextraction process have been studied and
      optimised by means of a categorical factorial design. Two extraction modes
      (direct SPME and headspace SPME) were tried at different extraction temperatures
      using four different fiber coatings [polydimethylsiloxane (PDMS), Carboxen (CAR)
      PDMS, PDMS-divinylbenzene (DVB) and Carbowax (CW)-DVB]. An extraction temperature
      of 100 degrees C sampling the headspace over the sample using CAR-PDMS or PDMS
      DVB as fiber coatings were found to be the experimental conditions that lead to a
      more effective extraction. The method proposed is very simple and yields high
      sensitivity, with detection limits in the low pg/ml, good linearity and
      repeatability for all the target compounds. The total analysis time, including
      extraction and GC analysis, was only 45 min. The optimised method performed well
      when it was applied to waste water from an urban treatment plant.

PMID- 12187982
TI  - Application of on-line solid-phase extraction-gas chromatography-mass
      spectrometry to the determination of endocrine disruptors in water samples.
AB  - We have applied a method based on solid-phase extraction (SPE), on-line coupled
      to gas chromatography-mass spectrometry through an on-column interface, to
      determine a group of endocrine-disrupting compounds in water samples. We have
      optimised the parameters affecting the SPE process and transfer step and used the
      method to analyse river, coastal and tap waters. In the full-scan acquisition
      mode, all the compounds were determined by preconcentrating only 15 ml of water
      sample. Di-n-butyl phthalate, benzylbutyl phthalate, bis(2-ethylhexyl) phthalate
      and bis(2-ethylhexyl) adipate at concentrations between 0.02 and 0.5 microg l(-1)
      were determined in some real samples.

PMID- 12187983
TI  - Analysis of anatoxin-a in aqueous samples by solid-phase microextraction coupled
      to high-performance liquid chromatography with fluorescence detection and on
      fiber derivatization.
AB  - A simple method for analysis of anatoxin-a in aqueous samples was developed using
      solid-phase microextraction (SPME) and high-performance liquid chromatography
      (HPLC) with fluorescence detection. Anatoxin-a was derivatized to a fluorogenic
      agent on the surface of the SPME fiber. In the method an SPME fiber was immersed
      for 30 min in the aqueous sample. The fluorogenic derivatizing reagent (4-fluoro
      7-nitro-2,1,3-benzoxadiazole, 1.0 mg/ml in methanol) was dropped or sprayed onto
      the fiber containing extracted analytes. The fiber was then heated for 10 min in
      an empty vial at 70 degrees C in a waterbath to promote derivatization. The
      derivatives formed on the fiber were desorbed in a SPME-HPLC interface. The
      interface was filled with methanol-1 mM hydrochloric acid (7:3, v/v) before
      inserting of the fiber into the interface. For desorption, the fiber was inserted
      in the interface for 5 min. For anatoxin-a in an aqueous sample, the calibration
      curve showed linearity in the range of 50-1500 ng/ml and the limit of detection
      of anatoxin-a was 20 ng/ml. No interferences were found, and the time for
      analysis was 55 min for one sample.

PMID- 12187984
TI  - Recovery, enrichment and selectivity in liquid-phase microextraction comparison
      with conventional liquid-liquid extraction.
AB  - Mathematical descriptions for extraction recovery and enrichment were applied for
      liquid-phase microextraction (LPME) and comparison with conventional two- and
      three-phase liquid-liquid extraction techniques (LLE) was made. The LPME
      theoretical calculations were verified by experimental determination of actual
      partition coefficients and by data obtained with LPME in a robust hollow fibre
      formate. With hollow fibre LPME operated in the two-phase mode, analytes were
      extracted from 1 to 4 ml aqueous samples into 25-50 microl of an organic solvent
      present in the pores and in the lumen of the porous hollow fibres. Compared with
      conventional two-phase LLE, two-phase LPME provided substantially higher
      enrichments for compounds with relatively large partition coefficients
      (K(org)/d>500). In contrast, because of the large volume of organic solvent
      relative to the sample volume, LLE provided high recovery and moderate enrichment
      even for compounds with relatively low partition coefficients (K(org)/d>5). Thus,
      two-phase LPME may be used for substantially enhanced extraction selectivity and
      enrichment of relatively hydrophobic analytes as compared with LLE whereas
      conventional two-phase LLE is superior for more hydrophilic analytes. Similar
      results were found for three-phase LPME where analytes where extracted from 1 to
      4 ml aqueous samples through approximately 20 microl organic solvent immobilized
      within the pores of the hollow fibre and into 25 microl of an aqueous acceptor
      solution inside the lumen of the hollow fibre. The fundamental differences of
      LPME and LLE were further demonstrated with practical experiments on extraction
      of the basic drugs promethazine, methadone, and haloperidol from human plasma and
      urine.

PMID- 12187985
TI  - Liquid-phase microextraction combined with capillary electrophoresis, a promising
      tool for the determination of chiral drugs in biological matrices.
AB  - A disposable device for liquid-phase microextraction (LPME) based on porous
      polypropylene hollow fibres has recently been introduced. In the present paper,
      LPME was combined with capillary electrophoresis (CE) and the combination was for
      the first time evaluated for chiral determination of drugs in biological
      matrices. The chiral antidepressant drug mianserin was selected as model
      compound. The mianserin enantiomers were extracted from 0.5 ml of plasma added
      internal standard and made alkaline with 0.25 ml of 2 M NaOH. The unionised
      analytes were extracted into di-n-hexyl ether impregnated in the pores of the
      hollow fibre, and into an acidic solution inside the hollow fibre. This resulted
      in a three-phase system where the extracts were aqueous, and hence directly
      compatible with the CE system. Efficient sample clean-up was seen and the
      extraction recovery was 80% for both enantiomers. Discrimination between the
      enantiomers in the extraction system was not observed. The limit of quantitation
      (S/N= 10; 12.5 ng/ml for both enantiomers) and the limit of detection (S/N=3; 4
      ng/ml for both enantiomers) were below the therapeutic range for mianserin. The
      method was validated and successfully applied to determine R- and S-mianserin in
      plasma samples from seven patients treated with mianserin, indicating that LPME
      CE is a promising combination for analysis of racemic drugs present in low
      concentrations in biological matrices.

PMID- 12187986
TI  - Methylmercury determination in biological samples by derivatization, solid-phase
      microextraction and gas chromatography with microwave-induced plasma atomic
      emission spectrometry.
AB  - A method for the extraction and gas chromatographic determination of
      methylmercury in biological matrices is presented. By combining the advantages of
      two extraction techniques-microwave-assisted extraction (MAE) and solid-phase
      microextraction (SPME)--the separation of methylmercury from biological samples
      is possible. Specifically, the procedure involves microwave extraction with 3 M
      hydrochloric acid, followed by aqueous-phase derivatization with sodium
      tetraphenylborate and headspace SPME with a silica fibre coated with
      polydimethylsiloxane (PDMS). For optimization of the derivatization-SPME
      procedure, a central composite experimental design with alpha = 1.682 and two
      central points was used to model gas-chromatographic peak areas as functions of
      pH, extraction temperature and sorption time. A desirability function was then
      used for the simultaneous optimization for methylmercury and Hg(II). The optimal
      derivatization-SPME conditions identified were close to pH 5, temperature 100
      degrees C, and sorption time 15 min. The identification and quantification of the
      extracted methylmercury is carried out by gas chromatography with microwave
      induced plasma atomic emission spectrometry detection. The validity of the new
      procedure is shown by the results of analyses of certified reference materials.

PMID- 12187987
TI  - Bio-compatible in-tube solid-phase microextraction capillary for the direct
      extraction and high-performance liquid chromatographic determination of drugs in
      human serum.
AB  - A restricted access material (RAM), alkyl-diol-silica (ADS), was used to prepare
      a highly bio-compatible solid-phase microextraction (SPME) capillary for the
      automated and direct in-tube extraction of several benzodiazepines from human
      serum. The bifunctionality of the ADS extraction phase prevented fouling of the
      capillary by protein adsorption while simultaneously trapping the analytes in the
      hydrophobic porous interior. This the first report of a restricted access
      material utilized as an extraction phase for in-tube SPME. The approach
      simplified the required apparatus in comparison to existing RAM column switching
      procedures, and more importantly eliminated the excessive use of extraction
      solvents. The biocompatibility of the ADS material also overcame the existing
      problems with in-tube SPME that requires an ultrafiltration or other
      deproteinization step prior to handling biological samples, therefore further
      minimizing the sample preparation requirements. The calculated oxazepam,
      temazepam, nordazepam and diazepam detection limits were 26, 29, 22 and 24 ng/ml
      in serum, respectively. The method was linear over the range of 50-50 000 ng/ml
      with an average linear coefficient (R2) value of 0.9998. The injection
      repeatability and intra-assay precision of the method were evaluated with five
      injections of a 10-microg/ml serum sample (spiked with all compounds), resulting
      in an average RSD<7%. The ADS extraction column was robust, providing many direct
      injections of biological fluids for the extraction and subsequent determination
      of benzodiazepines.

PMID- 12187988
TI  - Analysis of phenoxy herbicides in bovine milk by means of liquid-liquid-liquid
      microextraction with a hollow-fiber membrane.
AB  - A preconcentration technique, which involves liquid-liquid-liquid
      microextraction, was developed to determine phenoxy herbicides in bovine milk. A
      layer of organic phase was impregnated into the pores of a 3.5 cm long porous
      hollow fiber, while the internal volume of the fiber was filled with NaOH
      solution (the acceptor solution) that was connected directly to the needle of a
      microsyringe. The fiber was then immersed into 8 ml of acidified milk sample.
      When the sample solution was stirred, acidic analytes were extracted into the
      organic phase and back extracted simultaneously into the alkaline acceptor medium
      as the analytes were protonated at low pH and deprotonated at high pH. After
      extracting for a prescribed time, 5 microl acceptor solution was taken back into
      the syringe and injected directly into a HPLC system for quantification. The
      analytes were extracted quantitatively from the sample solution into the acceptor
      solution with a large enrichment factor of 900. Due to its low cost, the hollow
      fiber extraction device was disposed of after a single extraction that eliminated
      the possibility of carry over effects. In addition, because a small volume of
      organic solvent was required and little waste is generated, the procedure is
      environmentally friendly, and is compatible with the "green chemistry" concept.

PMID- 12187989
TI  - Determination of methylmercury in human hair by ethylation followed by headspace
      solid-phase microextraction-gas chromatography-cold-vapour atomic fluorescence
      spectrometry.
AB  - An analytical procedure for the determination of methylmercury in human hair
      after acid digestion using aqueous ethylation, headspace solid-phase
      microextraction sampling and final gas chromatography-cold-vapour atomic
      fluorescence spectrometry detection is described. Acid digestion, extraction
      procedure and chromatographic conditions were optimised. An optimal linear range
      using standard mercury solutions was found and concentration detection limits for
      the mercury species, MeHg and Hg2+, were about 50 and 80 ng/g, respectively, for
      100 mg of human hair. The reproducibility of the developed analytical procedure
      assessed for hair samples with incurred MeHg was better than 18% (n=5). A
      certified reference material from the National Institute of Environmental Studies
      (Japan) was used for validation. Analysis of human hair collected from urban
      inhabitants was performed and the mean value of methylmercury content in hair
      samples was 0.764 +/- 0.732 microg/g for the population tested. The developed
      analytical method is simple, fast and a suitable procedure for the monitoring and
      screening of human exposure to methylmercury.

PMID- 12187990
TI  - Comparison of solid-phase extraction methods for the determination of
      azaspiracids in shellfish by liquid chromatography-electrospray mass
      spectrometry.
AB  - Azaspiracids have been identified as the cause of a new toxic syndrome called
      azaspiracid poisoning (AZP) that has led to incidents of human intoxications
      throughout Europe following the consumption of mussels. Although five AZP toxins
      have been structurally elucidated to-date, azaspiracid (AZA1), 8
      methylazaspiracid (AZA2) and 22-demethylazaspiracid (AZA3) are the predominant
      toxins. Separation of the three main AZP toxins was achieved using reversed-phase
      liquid chromatography (LC) and coupled to an electrospray ionisation source of an
      ion-trap mass spectrometer. Five reversed-phase (C18) and three diol solid-phase
      extraction (SPE) cartridges were compared for their efficacy in the cleanup of
      shellfish matrix. The comparison was based on the optimum recoveries of AZA1,
      AZA2 and AZA3 from extracts of mussel tissues. LC-electrospray MS3 analysis was
      used to quantify the AZP toxins in wash and eluate fractions in the SPE studies.
      Good recovery and reproducibility data were obtained for one diol SPE cartridge
      and two C18 SPE cartridge types.

PMID- 12187991
TI  - Ultrasound extraction and thin layer chromatography-flame ionization detection
      analysis of the lipid fraction in marine mucilage samples.
AB  - This paper reports an analytical procedure based on ultrasound to extract lipids
      in marine mucilage samples. The experimental conditions of the ultrasound
      procedure (solvent and time) were identified by a FT-IR study performed on
      different standard samples of lipids and of a standard humic sample, before and
      after the sonication treatment. This study showed that diethyl ether was a more
      suitable solvent than methanol for the ultrasonic extraction of lipids from
      environmental samples because it allowed to minimize the possible oxidative
      modifications of lipids due to the acoustic cavitation phenomena. The optimized
      conditions were applied to the extraction of total lipid amount in marine
      mucilage samples and TLC-flame ionization detection analysis was used to identify
      the relevant lipid sub-fractions present in samples.

PMID- 12187992
TI  - Photolysis of polychlorinated biphenyls by solid-phase microextraction. "On
      fibre" versus aqueous photodegradation.
AB  - The photodegradation kinetics of polychlorinated biphenyls "on-fibre" is
      described. The utilisation of solid-phase microextraction (SPME) fibres to
      monitor photolysis pathways and determine photoproducts constitutes a new
      approach that exploits the solvent-free aspect and concentration possibilities of
      this technique. Direct photolysis of aqueous solutions containing polychlorinated
      biphenyls (PCBs) was also undertaken and SPME was used in this case for
      photoproduct extraction purposes. Reductive dechlorination was the main
      decomposition mechanism in both procedures. Less-chlorinated biphenyls are the
      principal photoproducts and, among these, some toxic coplanar species have been
      detected. The influence of irradiation time was evaluated for both treatments.
      SPME was found to be a good choice for the extraction of photoproducts in
      experiments conducted in the classical way (extraction after photolysis).
      Moreover, it is demonstrated that photolysis of PCBs "on fibre" is realistic and
      provides the possibility of evaluating the phototransformation of these
      pollutants at environmental levels.

PMID- 12187993
TI  - Determination of bisphenol-type contaminants from food packaging materials in
      aqueous foods by solid-phase microextraction-high-performance liquid
      chromatography.
AB  - A fast screening method consisting of off-line solid-phase microextraction
      coupled to HPLC and fluorescence detection, suitable for the analysis of several
      bisphenol derivatives and their degradation products in aqueous solution, has
      been developed. Detection limits of 0.7 ng ml(-1) for 2,2-bis[4
      (glycidyloxy)phenyl]propane, 0.9 ng ml(-1) for bisphenol A bis(3-chloro-2
      hydroxypropyl)ether, 1.1 ng ml(-1) for 2,2-bis(4-hydroxyphenyl)propane and 2.4 ng
      ml(-1) for bisphenol F diglycidyl ether have been achieved working in the linear
      range 10-500 ng ml(-1). The good analytical features achieved make the proposed
      method an interesting option for the direct determination of these compounds in
      aqueous canned food such as peas, tuna, olives, maize, artichokes or palm hearts.
      Both the optimization process and the results, including the analysis of real
      samples, are given and discussed.

PMID- 12187994
TI  - Development of a headspace solid-phase microextraction-gas chromatography-mass
      spectrometry method for the identification of odour-causing volatile compounds in
      packaging materials.
AB  - A method for the identification of volatile organic compounds in packaging
      materials is presented in this study. These compounds are formed by
      thermooxidative degradation during the extrusion coating process in the
      manufacture of packaging. Headspace solid-phase microextraction (HS-SPME) was
      used as sample preparation technique prior to the determination of the volatile
      organic compounds by gas chromatography-mass spectrometry (GC-MS). The effects of
      extraction variables, such as the type of fibre, the incubation temperature, the
      pre-incubation time, the size of the vial and the extraction time on the amounts
      of the extracted volatile compounds were studied. The optimal conditions were
      found to be: carboxen-polydimethylsiloxane 75 microm fibre, 5 min of pre
      incubation time, 100 degrees C of incubation temperature, 20-ml vial, and 15 min
      of extraction time. The chromatograms obtained by HS-SPME and static headspace
      extraction were compared in order to show that the HS-SPME method surpasses the
      static headspace method in terms of sensitivity. Twenty-five compounds were
      identified including carbonyl compounds (such as 3-methyl-butanal, 3-heptanone or
      octanal), carboxylic acids (such as pentanoic acid or hexanoic acid) known as
      odour causing compounds and hydrocarbons (such as decane, undecane or dodecane).
      Finally, the method was applied to different packaging samples (one odour
      unacceptable, two odour-acceptable, and three odourless samples) and to the raw
      materials in order to find out the odour-responsible volatile organic compounds
      and their source.

PMID- 12187995
TI  - Analysis of mono- and diesters of o-phthalic acid by solid-phase extractions with
      polystyrene-divinylbenzene-based polymers.
AB  - Retention mechanisms of an unmodified and a hydroxylated polystyrene
      divinylbenzene polymer were studied by solid-phase extraction of o-phthalic acid
      and some of its mono- and diesters from purified water and then analysing by GC
      MS. The monoesters and phthalic acid were retained only when protonated (i.e.
      acidified with HCI to pH 0.9). Of all elution solvents tested, ethyl acetate gave
      the best overall recoveries (61-89%) with both polymers. Applicability to complex
      matrixes (e.g. acidogenic landfill leachates) was examined by introducing a
      washing step with acetone in acidified water (pH 0.9) to eliminate volatile fatty
      acids (C2-C6) from the cartridge. Finally, the method was tested on real samples.

PMID- 12187996
TI  - Determination of adipate plasticizers in poly(vinyl chloride) by microwave
      assisted extraction.
AB  - A new method based on the application of microwave radiation to the extraction of
      adipate plasticizers from poly(vinyl chloride) PVC plastics is described. The
      experimental conditions for microwave-assisted extraction (i.e. extracting
      solvent, temperature, time and microwave power) were evaluated in terms of
      recovery. The optimisation was carried out with pastes of PVC plastified with di
      2-ethylhexyl adipate, and extracts were measured by gas chromatography with flame
      ionization detection. Six different adipate plasticizers were studied, and
      microwave-assisted extraction was compared with supercritical fluid extraction
      for the extraction of adipates and phthalates from PVC matrices. It has been
      observed that the microwave-assisted extraction parameters evaluated are tightly
      interconnected. It has been shown that the efficiency of microwave-assisted
      extraction depends on the kind of solvent, the temperature achieved and the
      heating time. Moreover, the final temperature reached depends on the microwave
      power, the number of vessels and the irradiation time. On the other hand,
      microwave-assisted extraction provides higher recovery values than supercritical
      fluid extraction for both phthalate and adipate plasticizers.

PMID- 12187997
TI  - Detection of explosives and their degradation products in soil environments.
AB  - Polynitro organic explosives [hexahydro-1,3,5-trinitro-1,3,5-triazine (RDX),
      octahydro-1,3,5,7-tetranitro-1,3,5,7-tetrazocine (HMX) and 2,4,6-trinitrotoluene
      (TNT)] are typical labile environmental pollutants that can biotransform with
      soil indigenous microorganisms, photodegrade by sunlight and migrate through
      subsurface soil to cause groundwater contamination. To be able to determine the
      type and concentration of explosives and their (bio)transformation products in
      different soil environments, a comprehensive analytical methodology of sample
      preparation, separation and detection is thus required. The present paper
      describes the use of supercritical carbon dioxide (SC-CO2), acetonitrile (MeCN)
      (US Environmental Protection Agency Method 8330) and solid-phase microextraction
      (SPME) for the extraction of explosives and their degradation products from
      various water, soil and plant tissue samples for subsequent analysis by either
      HPLC-UV, capillary electrophoresis (CE-UV) or GC-MS. Contaminated surface and
      subsurface soil and groundwater were collected from either a TNT manufacturing
      facility or an anti-tank firing range. Plant tissue samples were taken fromplants
      grown in anti-tank firing range soil in a greenhouse experiment. All tested soil
      and groundwater samples from the former TNT manufacturing plant were found to
      contain TNT and some of its amino reduced and partially denitrated products.
      Their concentrations as determined by SPME-GC-MS and LC-UV depended on the
      location of sampling at the site. In the case of plant tissues, SC-CO2 extraction
      followed by CE-UV analysis showed only the presence of HMX. The concentrations of
      HMX (<200 mg/kg) as determined by supercritical fluid extraction (SC-CO2)-CE-UV
      were comparable to those obtained by MeCN extraction, although the latter
      technique was found to be more efficient at higher concentrations (>300 mg/kg).
      Modifiers such as MeCN and water enhanced the SC-CO2 extractability of HMX from
      plant tissues.

PMID- 12187998
TI  - Optimization of parameters for the supercritical fluid extraction in the
      determination of N-nitrosamines in rubbers.
AB  - The study of the possibilities of supercritical fluid extraction (SFE) with N
      nitrosamines in rubbers has been carried out. Home-made materials fortified with
      several N-nitrosamines were prepared in order to optimize the SFE parameters. A
      Plackett-Burman design was employed to evaluate the influence of those parameters
      to be controlled in SFE, such as pressure, temperature, static and dynamic time,
      restrictor temperature and volume of modifier while CO2 was used as the
      extraction fluid. An extra central composite design for the main factors
      (according to the previously obtained results) was also developed in order to
      refine the best supercritical conditions for the extraction of N-nitrosamines
      from rubbers. Gas chromatography with a nitrogen and phosphorus sensitive
      detector was used to achieve sensitivity and limits of detection for the
      concentrations expected in plastic materials. The proposed analytical method has
      shown to be useful in the determination of N-nitrosamines even for complex
      matrices.

PMID- 12187999
TI  - Optimization of the extraction of azo colorants used in toy products.
AB  - Azo dyes are widely used in formulations intended for children use. But their
      potential toxicity raised the need of an efficient and fast method of analysis. A
      study for the optimization of the extraction of some azo colorants used in toys
      was conducted. Several extraction methods for the selected analytes were
      evaluated and compared, i.e., supercritical fluid extraction (SFE), microwave
      assisted extraction (MAE) and Soxhlet extraction. Poly(vinyl chloride) samples
      spiked with known quantities of the studied dyes were prepared. The influence of
      critical variables on analyte recoveries in SFE and MAE was investigated by using
      a full-level factorial design, where most significant parameters as well as order
      interactions were studied in each case. The analytes were subsequently detected
      by high-performance liquid chromatography with UV detection. The three extraction
      techniques were compared in terms of reproducibility, selectivity and analyte
      recoveries. MAE showed higher recoveries (above 98%), except for the diazo dye
      (nearly 60%). Reproducibilities were generally good for the three methods
      (relative standard deviation lower than 2.0%).

PMID- 12188000
TI  - Dynamic versus static sampling for the quantitative analysis of volatile organic
      compounds in air with polydimethylsiloxane-carboxen solid-phase microextraction
      fibers.
AB  - Polydimethylsiloxane-Carboxen solid-phase microextraction fibers are now well
      known to be very efficient trapping media for the analysis of volatile organic
      compound (VOC) traces in air. However, competitive adsorption, due to the nature
      of the coating, considerably limits analyte quantitation. In this contribution,
      different experimental conditions are investigated to achieve quantitative
      analysis. Static and dynamic sampling were compared for the analysis of 11 VOCs
      in a standard gaseous mixture at different extraction times (1, 5, 15 and 45
      min). The same experiments were performed with four isolated compounds.
      Adsorption results from gas mixture and isolated compounds were compared and a
      common linear range (i.e., where quantitative analysis is conceivable) was
      determined. When sampling was in the dynamic mode, compounds with lower affinity
      for the coating showed a very narrow linear range, meaning that competition for
      adsorption was quickly discriminative. The same experiments in static mode
      allowed one to obtain wider linear ranges for all compounds, especially for lower
      affinity compounds: for a 1 min sampling time, acetone showed a linear adsorption
      range from 3 to 60 microg m(-3) in the dynamic mode which extended from 5 to 300
      microg m(-3) in the static mode.

PMID- 12188001
TI  - Quantification of volatile sulfur compounds in complex gaseous matrices by solid
      phase microextraction.
AB  - Procedures were assessed for quantifying nine volatile sulfur compounds found in
      complex gaseous samples collected at a biogas-production plant and a sewage
      treatment plant. The target compounds were extracted by solid-phase
      microextraction (using the 75-microm Carboxen-polydimethylsiloxane fiber coating)
      at 22 degrees C for 20 min, and analyzed by GC-MS. Detection limits ranged
      between 1 pptv (v/v) for carbon disulfide and 470 pptv (v/v) for hydrogen
      sulfide. High amounts of organic compounds were found during full-scan analysis
      of the samples and standard additions to individual sub-samples revealed that the
      analysis was subject to matrix effects. However, the functions obtained by
      standard additions were still linear and quantification was possible for all the
      compounds tested except hydrogen sulfide. No detectable losses were observed
      during storage in the sampling containers, made of Tedlar film, over a storage
      period of 20 h. However, water permeated through the walls and the relative
      humidity in the bag increased during storage until it reached the ambient level.
      Finally, it was shown that the drying agent, CaCl2, caused no detectable losses
      of any of the compounds.

PMID- 12188002
TI  - Determination of polychlorinated biphenyl compounds in indoor air samples.
AB  - A simple procedure for the determination of six non-coplanar polychlorinated
      biphenyls (PCBs) in medium volumes of indoor air is described. Samples are forced
      at 6 m3/h through a device consisting of a quartz filter connected to the end of
      a conventional solid-phase extraction cartridge containing 60 mg of
      functionalized styrene-divinylbenzene. PCBs retained on the sorbent are directly
      eluted with 2 ml of hexane. Those associated to airborne particulate matter are
      microwave extracted in 10 min using 15 ml hexane-acetone (1:1). The proposed
      procedure is favorably compared to the use of polyurethane cylinders for the
      concentration of PCBs in terms of solvent consumption and rapidity of the
      desorption step. Furthermore, the functionalized sorbent showed higher
      breakthrough volumes than Amberlite XAD-2 for PCBs in gas phase. Quantification
      limits between 2 and 40 pg/m3 were obtained for six PCBs (from di- to
      heptachlorobiphenyls) using GC-electron-capture detection.

PMID- 12188003
TI  - On-line coupling of supercritical fluid extraction with high-performance liquid
      chromatography for the determination of explosives in vapour phases.
AB  - An analytical method for determining nitroaromatic explosives in vapour phases is
      presented. Samples were collected by pumping air through glass fibre filters and
      polyurethane foam adsorbents, and an on-line extraction system combining
      supercritical fluid extraction (SFE) and high-performance liquid chromatography
      (HPLC) was developed. This allows analytes to be transferred from the adsorbent
      to the HPLC system via a porous graphitic carbon trap. When using gradient
      elution with a suitable mobile phase, most of the nitroaromatic isomers tested
      were separated. The proposed method is fully automated, allows a complete
      analysis to be processed in less than 30 min, and it is compatible with most of
      the organic solvents commonly used as SFE modifiers or additives. The method has
      been applied to the analysis of real samples obtained from headspace sampling of
      military-grade 2,4,6-trinitrotoluene and has been shown to constitute a promising
      alternative for assessing whether areas are mined in landmine-clearing
      operations.

PMID- 12188004
TI  - Monitoring volatile compounds during dry-cured ham ripening by solid-phase
      microextraction coupled to a new direct-extraction device.
AB  - Key flavour volatile compounds were monitored during ripening of dry-cured ham by
      solid-phase microextraction (SPME) coupled to a new direct-extraction device
      (DED). DED allows the insertion of the SPME fibre into the core of solid
      materials with no damage to the fibre. This enables extraction of volatiles from
      solid foodstuffs while avoiding sample handling. Major groups of volatile
      compounds extracted with SPME-DED agreed with available scientific literature
      about dry-cured ham volatiles. Moreover, volatile compounds previously
      highlighted as quality markers in dry-cured ham, such as 3-methylbutanal or
      hexanal, were satisfactorily extracted using SPME-DED. Changes in the profile of
      volatile compounds throughout the processing followed a typical pattern of
      volatile compounds formation. Therefore, SPME-DED appears as a new and promising
      method for monitoring ripening of dry-cured hams with no depreciation of the
      product, which might substitute traditional subjective methods currently used in
      the ham processing industry. However, the use of the internal standard method is
      not possible with this technique. Therefore, results using SPME-DED only point
      out a trend in the volatile profile. Further attempts relating data obtained
      using SPME-DED in dry-cured hams with sensory and chemical data from the same
      samples would be necessary for optimising this method as a quality control method
      in dry-cured ham industries.

PMID- 12188005
TI  - Aroma analysis of fresh and preserved onions and leek by dual solid-phase
      microextraction-liquid extraction and gas chromatography-mass spectrometry.
AB  - The lachrymatory factor (thiopropanal-S-oxide) was directly analysed on fresh
      onion (Allium cepa) juice by solid-phase microextraction (polyacrylate fibre)
      using a fast routine GC-MS method on a 10 m x 0.32 mm I.D. (4 microm thick
      polydimethylsiloxane film) column with splitless mode injection. The
      identification and quantification of thiosulphinates and zwiebelanes were
      obtained on the same juice extracted by diethyl ether after 80 min maceration
      using the same GC-MS method. Selected ion recording enhanced the differentiation
      possibilities and the detection limits. This dual method was used to evaluate
      flavour differences between onion and shallot varieties as it provides accurate
      profiles of all initially formed compounds. Moreover, this method allowed us to
      compare qualitatively and quantitatively transformed products: frozen, freeze
      dried powders and sterilised products. Excepting the lachrymatory factor, frozen
      onion compounds were similar compared to those of fresh onion sample. Conversely,
      the other transformed samples have lost most of the initially formed compounds
      and produced mainly di- and trisulphides corresponding to the degradation of
      thiosulphinates and zwiebelanes. These dramatic changes can explain the very
      different flavours of these manufactured products compared to fresh material.

PMID- 12188006
TI  - Comparison of different coatings in solid-phase microextraction for the
      determination of organochlorine pesticides in ground water.
AB  - A solid-phase microextraction (SPME) procedure using three commercialised fibers
      (Carbowax-divinylbenzene, Carboxen-polydimethylsiloxane and divinylbenzene
      Carboxen-polydimethylsiloxane) is presented for the determination of a selected
      group of organochlorine compounds in water samples. The extraction performances
      of these compounds were compared using fibers with two and three coatings. The
      optimal experimental procedures for the adsorption and desorption of pesticides
      were determined. The limits of detection with the divinylbenzene-Carboxen
      polydimethylsiloxane fiber at levels below ng l(-1) were similar or lower than
      values presented in the literature for several of these compounds using
      polydimethylsiloxane fiber. The advantages of using this fiber, such as no salt
      addition, are discussed. Finally, the optimised procedures were applied
      successfully for the determination of these compounds in polluted ground water
      samples.

PMID- 12188007
TI  - Blood pressure measurement in epidemiological investigations in teenagers.
AB  - BACKGROUND: The use of sphygmomanometers may lead to problems in investigations
      on health of young people. The purpose of this paper is to present the validation
      of the blood pressure (BP) collected during the survey 'Youth Heart Health' in
      Hainaut by using second sample of young people in Hainaut for which BP was
      measured by a manual taking of tension and by an electronic device. METHODS:
      Validation was done with a control sample of 343 young with five successive BP
      measures: twice with the mercury sphygmomanometer and three with DXL. We compared
      the manual and the electronic measures in order to study the correlation between
      the two methods. The control sample was used in order to compare the BP
      measurements with the results of the survey on the health of young people in
      Hainaut. RESULTS: The differences between manual systolic BP and Dinamap measures
      are significant (differences in averages 3.6 mmHg; d.s. 7.8; 95% CI: 2.8-4.4
      mmHg; p < 0.001) and the regression coefficient is -0.015. Diastolic BP is
      significantly higher with the manual method than with Dinamap (differences in
      means: 8.2 mmHg; d.s. 7.0; 95% CI: 7.4-8.9 mmHg; p < 0.001) and the coefficient
      of regression is 0.096. We observe a difference in BP between the general survey
      and the control group (10.3 mmHg for systolic manual control and of 10.9 mmHg for
      systolic electronic control; 3.3 mmHg for diastolic manual control and of 11.5
      mmHg for diastolic electronic control). CONCLUSIONS: The values of BP of the
      'Youth Heart Health' are significantly higher. These observations indicate the
      difficulties in the choice of the tool for measurements of BP in epidemiological
      investigations in the teenagers. In order to decrease skews of observations in
      the measurement of BP, it is recommended to use a valid electronic instrument.
      Dinamap XL is an instrument of choice in such studies of young people.
      Environmental and organisational factors may also explain the observed
      difference, which means that survey's protocols should address this issue
      carefully.

PMID- 12188008
TI  - Random errors in the measurement of 10 cardiovascular risk factors.
AB  - Random errors in the measurement of 10 commonly investigated cardiovascular risk
      factors (systolic and diastolic blood pressure, blood cholesterol, blood glucose,
      pulse rate, body mass index (BMI), cigarette consumption, passive smoking,
      alcohol intake and physical exercise) were assessed in a general population
      cohort (n = 2517) and a workforce cohort (n = 8008). Random errors were estimated
      from regression dilution ratios (lower ratios imply greater random error, and a
      ratio of one implies no random error). All of the risk factors, except for BMI
      (which had regression dilution ratios of 0.93 and 0.98 in the two cohorts), were
      measured with substantial levels of random error. Particularly low regression
      dilution ratios were observed for physical exercise (0.28 and 0.39) and pulse
      rate (0.47 and 0.56). For each of these risk factors, with the possible exception
      of BMI, associations with long-term average values could be importantly biased
      toward the null unless appropriate corrections are made.

PMID- 12188009
TI  - Relationship between plasma leptin levels and lipid profiles among school
      children in Taiwan--the Taipei Children Heart Study.
AB  - Leptin, an adipose tissue-derived of gene product, is important in energy
      metabolism. However, the role of leptin in the metabolism of lipids is still not
      clear in humans. The purpose of this study was to evaluate the association of
      plasma leptin concentrations and lipid profiles among school children in Taiwan.
      After multistage sampling of 85 junior high schools in Taipei, we randomly
      selected 1264 children (617 boys and 647 girls) aged 12-16 years for this study.
      We measured the anthropometric variables, lifestyle factors and biochemical
      parameters among these children. Anthropometric measurements included body height
      (BH) and weight (BW) and we calculated body mass index (BMI) as the ratio of the
      BW to the square of the BH, expressed in kg/m2. Plasma leptin levels were
      measured by radioimmunoassay. We also measured lipid profiles including serum
      total cholesterol (CHOL), triglyceride (TG), high density lipoprotein-cholesterol
      (HDL-C), apolipoprotein-A1 (Apo-A1), apolipoprotein-B (Apo-B), and lipoprotein(a)
      (Lp(a)) levels, and calculated low density lipoprotein-cholesterol (LDL-C) levels
      and CHOL to HDL-C ratio (TCHR). Girls had higher leptin, CHOL, TG, HDL-C, (LDL
      C), Apo-A1, Apo-B, and Lp(a) levels and lower BMI than boys did. Plasma leptin
      concentrations were significantly positively correlated with TG, LDL-C, and Apo
      B, but negatively with HDL-C and Apo-A1 in both the genders. Children with higher
      plasma leptin levels (>75th percentiles) have significantly higher TG, HDL-C, LDL
      C, TCHR, and Apo-B than those with relatively lower leptin levels. In
      multivariate regression analyses, the association between plasma leptin level and
      lipid profiles (such as CHOL, TG, and Apo-B) were still significant (p < 0.05)
      even after adjusting for BMI among boys. However, this association became
      attenuated and insignificant among girls. Finally, in the model that included the
      standard covariates, plasma leptin was the most predictive of CHOL, TG and Apo-B
      levels among those school children in Taiwan. Our results suggest that plasma
      leptin and BMI were independently associated with the lipids and lipoprotein
      profiles among Taiwanese Children. In both genders, children in the top 25% of
      the leptin distribution have more adverse lipid and lipoprotein profiles.

PMID- 12188011
TI  - Hepatitis A seroprevalence in Slovene travellers.

PMID- 12188010
TI  - Weight change among self-reported dieters and non-dieters in white and African
      American men and women.
AB  - Few studies have examined the association between dieting and weight change in
      general population and results have been inconsistent. To the best of our
      knowledge, no such study has been done in middle-aged African Americans. We
      examined 10,554 white and African American men and women who were participants in
      the Atherosclerosis Risk in Communities (ARIC) Study and attended examinations
      between 1986 and 1994. We found that the prevalence of dieting in white women,
      white men, African American women, and African American men was 6.5, 2.3, 3.5,
      and 0.9%, respectively. After controlling for the covariates, the difference in
      the mean annual weight gain between dieters and nondieters was 0.61, 0.46, and
      0.59 kg/year among white women, white men, and African American women,
      respectively. In conclusion, in this cohort of white men and women and African
      American women aged 45-64 years, self-reported dieting was associated with a
      larger mean annual weight gain than non-dieting over a period of 6 years.

PMID- 12188012
TI  - Prevalence of antibodies to Rickettsia typhi in an area of the center of Spain.
AB  - It was the aim of the present work to evaluate Rickettsia typhi antibody
      prevalence in 'Comunidad Autonoma de Madrid' (CAM), an area in the centre of
      Spain. A total of 640 serum samples from the general population were tested by an
      indirect immunofluorescence assay. Specific R. typhi antibodies were found in 44
      (6.8%) of the samples. The present survey results demonstrate the occurrence of
      R. typhi human infections in this area.

PMID- 12188013
TI  - Urease-positive Trichophyton rubrum strains (previously described as T.
      raubitschekii): first isolations in Argentina.
AB  - The present study reports the first Argentinian human cases of tinea caused by
      urease-positive Trichophyton rubrum strains (corresponding to isolates previously
      described as T. raubitschekii) in order to supply geographical data for these
      strains that are very rarely isolated as agents of dermatophytosis. The two
      isolates were identified by morphological, cultural, and physiological
      characteristics. The strains were isolated from cases of tinea corporis and tinea
      unguium.

PMID- 12188014
TI  - Estimating the number of opiate users in amsterdam by capture-recapture: the
      importance of case definition.
AB  - One of the objectives of Amsterdam's methadone maintenance treatment is
      maximising its coverage among problematic opiate users. In order to evaluate what
      proportion is reached, the capture-recapture method is conducted to estimate the
      prevalence of problematic opiate use. Samples of opiate users in contact with
      police, hospital or treatment are used. The treatment sample is limited to the
      low threshold treatment sample (treatment with minimal requirements to the
      clients). Based on differences of log likelihood ratio, Akaike's and Bayesian
      information criteria, log linear models are selected. The size of the population
      of problematic opiate users in 1997 is estimated to be 4130 (95% confidence
      interval: 3753-4566). Within 3 months 50% was registered: 16% at the police, 2.5%
      at the hospital and 40% at treatment. This study shows that the Amsterdam
      methadone treatment programs succeed in reaching a high proportion of problematic
      opiate users. The estimation of the prevalence of problematic opiate users is
      considered to be valid. However, if, instead of the low threshold treatment, the
      total treatment sample had been used, the population of interest and the sampled
      population would not match correctly, and prevalence would have been
      overestimated.

PMID- 12188015
TI  - A screening procedure detecting high-yield candidates for OGTT. The Women's
      Health in the Lund Area (WHILA) study: a population based study of middle-aged
      Swedish women.
AB  - The objective was to evaluate a screening procedure for detecting high-yield
      candidates for an OGTT, in a population of middle-aged Swedish women. A two-step
      screening procedure was performed in 6917 subjects. Women with a positive
      screening outcome, i.e. increased non-fasting capillary blood glucose, serum
      triglycerides, BMI, WHR, blood pressure or a family history of diabetes,
      pharmacological treatment of hypertension or hyperlipidaemia at the primary
      screening underwent a 75-g OGTT. A control group of women with negative screening
      outcome (n = 221) also underwent an OGTT. In 2923 women with positive screening
      outcome, 517 (17.7%) had NFG/IGT (normal fasting venous blood glucose <5.6 mmol/l
      and 2h-glucose 6.7-9.9 mmol/l), 109 (3.7%) IFG/IGT (fasting 5.6-6.0 and 2h 6.7
      9.9 mmol/l) and 223 (7.6%) diabetes (fasting > or = 6.1 or 2h > or = 10.0
      mmol/l). These figures were three, five and four times higher, respectively, than
      in the control group with negative screening outcome (p < 0.001 for all); no
      differences were found for IFG/NGT (fasting 5.6-6.0 and normal 2h < 6.7 mmol/l)
      (4.6% vs. 7.2%). For predicting impaired glucose metabolism (IFG/NGT, NFG/IGT,
      IFG/IGT, diabetes), the screening instrument showed an estimated sensitivity of
      70%, specificity of 55%, positive predictive value of 34% and negative predictive
      value of 85%, based on findings in the control sample. The odds ratio for NFG/IGT
      increased with the numbers of risk factors from 2.8 to 7.7, for IFG/ IGT from 5.7
      to 55.0 and for diabetes from 2.5 to 18.1. High B-glucose, WHR and BMI were the
      three most important factors associated with an increased risk for NFG/IGT,
      IFG/IGT and diabetes. In subjects with IFG/NGT, none of the screening variables
      was associated with an increased risk. In summary, the results show a population
      screening method focused on features of the metabolic syndrome that discloses
      high-yield candidates for OGTT. A high prevalence of unknown impaired glucose
      metabolism was found in middle-aged women with a positive screening profile.

PMID- 12188017
TI  - Mortality from non-malignant respiratory diseases in Andalusia, Spain, 1975-1997.
AB  - This study aims to assess mortality trends of nonmalignant respiratory diseases
      from 1975 through 1997 in the population of Andalusia (a region of Spain in the
      southwest, population 7,000,000). The death records containing codes 460-519 of
      the International Classification of Diseases, Eighth Revision (ICD-8) and Ninth
      Revision (ICD-9) in effect through the 23-year period were used in this study.
      Deaths from nonmalignant respiratory diseases accounted for 12.4 and 10% of all
      deaths in males and females in 1975 and for 12.1 and 8.3% in 1997. Crude death
      rates decreased from 107.5 to 102.7 per 100,000 amongst men, and from 76.9 to
      62.2 per 100,000 amongst women. Age-adjusted death rates decreased from 167.6 to
      111.6 per 100,000 in men and from 84.4 to 41.2 per 100,000 in women. Age-adjusted
      death rate by potential years of life lost decreased from 5.8 to 2.4 per 1000 in
      men and from 2.4 to 0.8 per 1000 in women. Total percentage of change, adjusted
      by age, showed a decrease of 24.3% in men and 45.9% in women. Gender-adjusted
      rates for each category of nonmalignant respiratory disorders showed an upward
      trend of obstructive lung diseases in men and a downward trend of diseases of the
      upper airways and pneumonia both in men and women. Specific death rates by age
      groups for 1975-1985 and 1986-1997 showed an increased in mortality in infants
      under 1 year of age and in abrupt decrease up to the age of 50 followed by an
      exponential increase up to the age of 85.

PMID- 12188016
TI  - Variables associated with fibrinogen in a population-based study: interaction
      between smoking and age on fibrinogen concentration.
AB  - The aim of the study was to assess the association between fibrinogen and other
      cardiovascular risk factors. A cross-sectional population-based study in Gerona
      (Spain) was designed, 1544 subjects (747 men, 797 women) participated.
      Anthropometric measurements, blood pressure and blood samples were obtained.
      Fibrinogen was measured by a coagulometric method. Smoking habits, alcohol
      consumption and physical activity practice were recorded by questionnaires.
      Fibrinogen was directly related to age, body mass index (BMI) and female gender
      and inversely to alcohol and moderate-heavy physical activity practice.
      Fibrinogen was also higher in men and young women who smoked. In the multivariate
      analysis, age (regression coefficient (RC): 1.33; standard error (SE): 0.13; unit
      = 1 year), female gender (RC: 12.24; SE: 3.56) and BMI (RC: 1.83; SE: 0.39; unit
      = 1 kg/m2) were directly associated with fibrinogen, whereas alcohol (RC: -0.04;
      SE: 0.01; unit = 1 g/d) was inversely associated. A statistically significant
      interaction between smoking and age was observed. Age was the strongest variable
      associated with fibrinogen and modifies the association between smoking and
      fibrinogen; the magnitude of this association increases with age.

PMID- 12188018
TI  - Cancer risk in the reindeer breeding Saami population of Sweden, 1961-1997.
AB  - The Saami people are the natives of northern Scandinavia and the Kola Peninsula.
      In a cohort of 2033 Swedish reindeer breeding Saamis, the cancer risks between
      1961 and 1997 were studied. In total, 193 cases of cancer were observed versus
      322 expected in the general Swedish population and 249 in a geographically
      matched reference population of non-Saamis. In comparison to non-Saamis living in
      the same area, the reindeer breeding Saamis showed a statistically significant
      lower risk of developing cancer of the prostate and of malignant lymphoma,
      whereas the risk of stomach cancer was significantly higher. Although there were
      no statistically significant changes of cancer risks over time, temporal trends
      were indicated towards a decreased risk of cancer in the stomach and the
      prostate. The results suggest that the explanations of the low cancer risk of the
      reindeer breeding Saamis, in relation to the non-Saamis in the same environment,
      are to be found among lifestyle and/or genetic factors.

PMID- 12188019
TI  - Helicobacter pylori infection in pre-term infants monitored during
      hospitalization.

PMID- 12188020
TI  - Can we separate active from inactive conformations?
AB  - Molecular modeling methodologies such as molecular docking, pharmacophore
      modeling, and 3D-QSAR, rely on conformational searches of small molecules as a
      starting point. All of these methodologies seek conformations of the small
      molecules as they bind to target proteins, i.e., their active conformations. Thus
      the question as to whether active conformations can be separated from inactive
      conformations is extremely relevant. In this paper, 3D-descriptors that separate
      random conformations from active conformations of small molecules are sought. To
      select appropriate descriptors, 65 protein-ligand complexes were taken from the
      protein data bank. For each ligand the active conformation was compared to
      randomly generated low energy conformations. Descriptors such as solvent
      accessible surface area, number of internal interactions and radius of gyration
      appear to be useful for separating the active conformations from the random
      conformations. The results with all these descriptors indicate that active
      conformations are less compact that random conformations, i.e., they have more
      solvent accessible surface area, fewer internal interactions and a larger radius
      of gyration than random conformations. Thus these descriptors could be useful as
      weights to bias conformational search procedures to conformations more likely to
      bind to proteins or as filters to eliminate conformations unlikely to bind to any
      protein.

PMID- 12188021
TI  - Modified AutoDock for accurate docking of protein kinase inhibitors.
AB  - Protein kinases are an important class of enzymes controlling virtually all
      cellular signaling pathways. Consequently, selective inhibitors of protein
      kinases have attracted significant interest as potential new drugs for many
      diseases. Computational methods, including molecular docking, have increasingly
      been used in the inhibitor design process [1]. We have considered several docking
      packages in order to strengthen our kinase inhibitor work with computational
      capabilities. In our experience, AutoDock offered a reasonable combination of
      accuracy and speed, as opposed to methods that specialize either in fast database
      searches or detailed and computationally intensive calculations. However,
      AutoDock did not perform well in cases where extensive hydrophobic contacts were
      involved, such as docking of SB203580 to its target protein kinase p38. Another
      shortcoming was a hydrogen bonding energy function, which underestimated the
      attraction component and, thus, did not allow for sufficiently accurate modeling
      of the key hydrogen bonds in the kinase-inhibitor complexes. We have modified the
      parameter set used to model hydrogen bonds, which increased the accuracy of
      AutoDock and appeared to be generally applicable to many kinase-inhibitor pairs
      without customization. Binding to largely hydrophobic sites, such as the active
      site of p38, was significantly improved by introducing a correction factor
      selectively affecting only carbon and hydrogen energy grids, thus, providing an
      effective, although approximate, treatment of solvation.

PMID- 12188022
TI  - Flexible docking under pharmacophore type constraints.
AB  - FLEXX-PHARM, an extended version of the flexible docking tool FLEXX, allows the
      incorporation of information about important characteristics of protein-ligand
      binding modes into a docking calculation. This information is introduced as a
      simple set of constraints derived from receptor-based type pharmacophore
      features. The constraints are determined by selected FLEXX interactions and
      inclusion volumes in the receptor active site. They guide the docking process to
      produce a set of docking solutions with particular properties. By applying a
      series of look-ahead checks during the flexible construction of ligand fragments
      within the active site, FLEXX-PHARM determines which partially built docking
      solutions can potentially obey the constraints. Solutions that will not obey the
      constraints are deleted as early as possible, often decreasing the calculation
      time and enabling new docking solutions to emerge. FLEXX-PHARM was evaluated on
      various individual protein-ligand complexes where the top docking solutions
      generated by FLEXX had high root mean square deviations (RMSD) from the
      experimentally observed binding modes. FLEXX-PHARM showed an improvement in the
      RMSD of the top solutions in most cases, along with a reduction in run time. We
      also tested FLEXX-PHARM as a database screening tool on a small dataset of
      molecules for three target proteins. In two cases, FLEXX-PHARM missed one or two
      of the active molecules due to the constraints selected. However, in general
      FLEXX-PHARM maintained or improved the enrichment shown with FLEXX, while
      completing the screen in considerably less run time.

PMID- 12188023
TI  - Internally defined distances in 3D-quantitative structure-activity relationships.
AB  - A new type of 3D-QSAR descriptors is introduced. For each molecule under
      consideration an internal coordinate system is defined relative to molecular
      points, such as positions of atoms in the molecule or centers of mass or certain
      substructures. From the origin of this system distances to the solvent accessible
      surface are calculated at defined spherical coordinate angles, theta and phi. The
      distances represent steric features, while the molecular electrostatic potentials
      at the intersection points with the surface represent the electrostatic
      contributions. The approach is called IDA (internal distances analysis). Matrices
      obtained by varying the spherical coordinate angles by fixed increments are
      correlated with the biological activity by partial least squares (PLS). The
      descriptors, tested with the benchmark steroids and an also well characterized
      benzodiazepine data set, turn out to be highly predictive. Additionally, they
      share the advantage of grid-based methods that the obtained models can be
      visualized, and thus be directly used in a rational drug design approach.

PMID- 12188024
TI  - Charge-transfer interactions in the inhibition of MAO-A by phenylisopropylamines-
      a QSAR study.
AB  - The HOMO energies and the charges on the aromatic carbons of two sets of MAO-A
      inhibiting phenylisopropylamines, one containing 4-amino substituents, were
      calculated by the AM1 method, in order to evaluate the importance of charge
      transfer interactions between drug and enzyme. Multiple-linear regressions of the
      pIC50 values on the calculated descriptors were performed with 33 compounds from
      the two sets, and separately with each set. A poor correlation was obtained when
      the two sets were merged, as a result of opposing trends shown by the two
      separate sets. These opposing trends were reconciled by invoking a partial
      protonation of the basic 4-amino substituents by a hydrogen-bond-donor fragment
      of the enzyme. The resulting analysis indicated that electron-rich rings and
      higher HOMO levels tended to increase activity. This model received support from
      the evaluation of the IMAO activity of four new phenylisopropylamines.

PMID- 12188025
TI  - A pilot study of perilymphatic leukocyte cytokine mixture (IRX-2) as neoadjuvant
      treatment for early stage cervical carcinoma.
AB  - Clinical and experimental data demonstrate that local cytokines are able to
      induce tumor regression and in some cases antitumor systemic immune response. IRX
      2 is a cell-free mixture of cytokines obtained from unrelated donor lymphocytes
      with demonstrated ability to induce immune mediated regression of squamous cell
      carcinomas of head and neck. The objective of this study was to evaluate the
      antitumor activity and toxicity of IRX-2 in untreated early stage cervical cancer
      patients. Ten consecutive patients clinically staged IB1, IB2 and IIA were
      treated with a neoadjuvant immunotherapy regimen that consisted in a single IV
      dose of cyclophosphamide at 300 mg/m2 on day 1, oral indomethacin or ibuprofen
      and zinc sulfate were administered from days I to 21 and 10 regional
      perilymphatic injections of IRX-2 on days 3 to 14. All patients were scheduled
      for radical hysterectomy on day 21. The clinical and pathological responses,
      toxicity and survival were evaluated. Clinical response was seen in 50% of
      patients (three partial responses, two minor responses). Seven patients underwent
      surgery and pathological tumor reduction associated with tumor fragmentation was
      found in five cases. Histological studies demonstrated a rather heterogeneous
      cell type infiltrating pattern in the tumor which included lymphocytes, plasma
      cells, neutrophils, macrophages and eosinophils. Immunohistochemical analysis of
      the surgical specimens demonstrated an increase of tumor infiltrating CD8+ cells.
      The treatment was well tolerated except for mild pain and minor bleeding during
      injections and gastric intolerance to indomethacin. At 31 months of maximum
      follow-up (median 29), eight patients are disease-free. Our results suggest that
      the immunotherapy approach used induces tumor responses in cervical cancer
      patients. Further studies are needed to confirm these results as well as to
      elucidate the mechanisms underlying these effects.

PMID- 12188026
TI  - Immunomodulatory effects of vitamin D receptor ligands in autoimmune diseases.
AB  - The active form of vitamin D, 1,25-Dihydroxyvitamin D3 [l,25(OH)2D3], is a
      secosteroid hormone that binds to the vitamin D receptor (VDR), a member of the
      superfamily of nuclear receptors for steroid hormones, thyroid hormone, and
      retinoic acid. VDR ligands regulate calcium and bone metabolism, control cell
      proliferation and differentiation, and exert immunoregulatory activities. The
      immunoregulatory properties of VDR ligands are currently exploited clinically for
      the topical treatment of psoriasis, a Th1 cell-mediated autoimmune disease of the
      skin, but recent advances in understanding their functions and novel insights
      into the immunomodulatory mechanisms they control suggest a wider applicability
      in the treatment of autoimmune diseases. In addition to direct effects on T cell
      activation, VDR ligands modulate with different mechanisms the phenotype and
      function of antigen-presenting cells (APCs), and, in particular, of dendritic
      cells (DCs). In vitro and in vivo experiments have shown that VDR ligands induce
      DCs to acquire tolerogenic properties that favor the induction of regulatory
      rather than effector T cells. These intriguing actions of VDR ligands have been
      demonstrated in several experimental models and could be exploited, in principle,
      to treat a variety of human autoimmune diseases.

PMID- 12188027
TI  - Induction of secretory and tumoricidal activities in peritoneal macrophages by
      ginsan.
AB  - The immunomodulatory effect of ginsan based on the production of cytokines and
      the activation of macrophage was studied. Murine peritoneal macrophages (PM) on
      in vitro treatment with ginsan isolated from Panax ginseng induced mRNA of
      cytokines such as tumor necrosis factor (TNF)-alpha, interleukin-1 (IL-1)beta,
      interleukin-6 (IL-6) and interleukin-12 (IL-12); TNF-alpha mRNA induction was
      maximum within 3 h, IL-6 mRNA was gradually induced up to 24 h, and IL-1beta and
      IL-12 mRNA were highly induced at 24 h. IL-1beta and IL-6 protein levels also
      increased within 24 h in a dose-dependent manner and reached a maximum with 100
      microg/ml ginsan. IL-12 was induced after 3 days and a high level of induction
      was detected after 4 days post treatment. Ginsan enhanced the lytic death of L929
      cells through TNF-alpha activation. The mRNA expression of nitric oxide synthase
      (iNOS) was highly induced after 24 h treatment of ginsan, and then NO production
      was maximum after 48-h treatment with a low dose of 1 microg/ml. The level of
      iNOS mRNA induction by ginsan was slightly less than that of macrophages
      activating agents such as LPS plus IFN-gamma. The tumoricidal activity of
      macrophage cultured with ginsan on Yac-1 cells was enhanced in a dose-dependent
      manner; growth inhibition increased 1.6-fold with 100 microg/ml ginsan. These
      results suggest that ginsan exerts as an effective immunomodulator and enhances
      antitumor activity of macrophages.

PMID- 12188028
TI  - Preventive effects of a verapamil against tumor necrosis factor-alpha-induced
      shock symptoms: approached from lipoprotein metabolic disorders.
AB  - We examined the role of intracellular Ca2+ in the mechanism of the preventive
      effects of the Ca2+-channel blocker verapamil against lipoprotein disturbances
      during tumor necrosis factor (TNFa)-induced shock syndrome. The heparin
      releasable lipoprotein lipase (LPL) activity in plasma of TNFalpha (5 X 10(4)
      units/mouse, i.v.)-injected mice was markedly lower at 4 h post-intoxication than
      in the controls. In mice treated with verapamil (10 mg/kg, s.c.), the activity of
      LPL 4 h after TNFalpha injection was significantly higher than in mice treated
      with TNFalpha alone. On the other hand, on polyacrylamide gel disk
      electrophoresis, very low density lipoprotein (VLDL) and high density lipoprotein
      (HDL) fractions in the sera of TNFalpha-injected mice were increased and reduced,
      respectively, relative to the controls. The administration of verapamil clearly
      prevented the lipoprotein damage arising from TNFalpha challenge. We investigated
      whether verapamil could suppress TNFalpha generation in endotoxin-treated J774A.1
      cells. Treatment with verapamil (30 microM) markedly inhibited endotoxin (1
      microg/ml)-induced TNFalpha production in these cells. These findings suggest
      that the concentration of intracellular Ca2+ may contribute to the extent of
      lipoprotein disturbances in plasma, which results from LPL suppression in
      TNFalpha-induced shock syndrome. Verapamil may, therefore, protect against some
      of the various disturbances caused by changes in Ca2+ mobilization through its
      ability to inhibit TNFalpha production in septic shock.

PMID- 12188030
TI  - Evaluation of gene expression in human lymphocytes activated in the presence of
      melatonin.
AB  - The effect of melatonin on the expression of genes previously correlated to T
      lymphocyte activation (HLA-DRB, thymosin beta 10 (beta-Tim)) and to Lymphokine
      Activated Killer (LAK) activity (beta-Tim, Tumour Rejection Antigen (TRA 1), nRap
      2) was investigated in phytohemagglutinin (PHA)-stimulated human lymphocyte
      cultures. The aim was to find an enhancing effect of this substance on anti
      tumoral immune defences as suggested by studies on tumour progression in mice and
      clinical immunotherapy trials in humans. mRNA obtained from melatonin-treated and
      -untreated PHA-stimulated lymphocytes was retrotranscribed and amplified by RT
      PCR using primers based on the sequences of the selected genes. The results
      suggest that melatonin does not increase T and LAK cell responses: in fact, a
      reduction in the transcription of all the considered genes was observed. These
      data are correlated with the antiproliferative effect of melatonin observed in in
      vitro treated lymphocytes.

PMID- 12188029
TI  - Immunomodulatory and anti-inflammatory effects of Kalanchoe brasiliensis.
AB  - The immunomodulatory effect of juice obtained from leaves of Kalanchoe
      brasiliensis (Kb) on zymosan-induced inflammation was investigated. C57B110 mice
      received a subcutaneous injection of 150 microg zymosan in the footpad. After 7
      days, there was an increase in footpad thickness from 176 +/- 4 to 236 +/- 9 x
      10(-2) mm and in blood flow in the footpad area, monitored by 99mTc, from 98 +/-
      4 to 694 +/- 59 counts per minute (cpm). Zymosan induced a severe infiltration of
      leukocytes into the articular tissues and a 13-fold increase in the adjacent
      popliteal lymph node (PLN) weight. Beginning 2 days after the injection, mice
      were treated daily for 5 days with different concentrations of lyophilised Kb
      juice dissolved in water. Treatment with 480 mg/kg/day reduced footpad thickness
      to 193 +/- 5 x 10(-2) mm, leukocyte infiltration and blood flow to 150 +/- 18 cpm
      in the footpad area. PLN weight in zymosan-injected mice decreased from 6.5 +/-
      0.5 to 1.5 +/- 0.4 mg, similarly to the decrease after treatment with
      indomethacin (3 mg/kg/day). Flow cytometric analysis of lymph node cells showed
      an important reduction in B cell number in Kb-treated mice. Treatment over a
      period of 10 days was also effective at reducing zymosan-induced inflammation,
      even when started 7 days after injection. These data suggest anti-inflammatory
      and immunosuppressive effects of K. brasiliensis that may account for its
      popularity in folk medicine against rheumatic diseases.

PMID- 12188031
TI  - Serotonin, 5-hydroxyindoleacetic acid and serotonin transporter in blood
      peripheral lymphocytes of patients with generalized anxiety disorder.
AB  - Several immune system modifications have been reported in pathological anxiety,
      such as generalized anxiety, panic and obsessive-compulsive disorders. Since
      serotonin transporter is a marker of peripheral blood lymphocytes and it is
      modified in major depression, the aim of the present work was to evaluate this
      transporter by the binding of [3H]paroxetine to membrane preparations of blood
      peripheral lymphocytes from control subjects and patients with generalized
      anxiety disorder. The number of transporters and the affinity for the ligand did
      not differ among the two groups. Serotonin and 5-hydroxyindoleacetic acid (5HIAA)
      were determined in platelet-rich and -poor plasma, and in lymphocytes.
      Nonsignificant changes were found in the patients as compared to controls.
      However, there was a significant positive correlation between serotonin
      concentration in platelet-poor plasma and in lymphocytes in the patients, but not
      in the controls. This finding might be an indication of a poor regulation of the
      transporter function by which serotonin plasma concentration might influence
      lymphocyte serotonin concentration. Previous results indicate that serotonin
      transporter is reduced in these cells in major depression disorder; however, in
      generalized anxiety disorder, the number of transporters was not modified,
      although the functional efficiency of serotonin transporter might be altered.

PMID- 12188032
TI  - Effect of orally administered Hochu-ekki-to, a Japanese herbal medicine, on
      contact hypersensitivity caused by repeated application of antigen.
AB  - The effects of oral administration of Hochu-ekki-to (HET; bu-zhong-yi-qi-tang in
      Chinese), a traditional Japanese and Chinese herbal medicine, on chronic contact
      hypersensitivity were investigated. HET suppressed ear swelling due to chronic
      contact hypersensitivity caused by repeated application of 2,4,6-trinitro-1
      chlorobenzene (TNCB). HET significantly suppressed not only increases in hapten
      specific immunoglobulin E (IgE) and IgG1 titer due to repeated application of
      TNCB, but also total IgE and IgG1 concentration in the serum. Interleukin 4 (IL
      4) level in inflamed ear tissue was significantly increased by repeated
      application of TNCB, and this increase in IL-4 level in the ear was significantly
      suppressed by oral administration of HET. Interferon gamma (IFN-gamma), IL-2, IL
      5, IL-10 and IL-12 levels are not changed as much as IL4 by TNCB and HET did not
      alter these cytokines as much as IL-4. These results suggest that oral
      administration of HET suppresses chronic contact hypersensitivity, and it can be
      assumed that the suppression of serum Ig E and Ig G1 and IL-4 in inflamed ear.

PMID- 12188033
TI  - Comparison of in vivo efficacy of BCX-1777 and cyclosporin in xenogeneic graft
      vs.-host disease: the role of dGTP in antiproliferative action of BCX-1777.
AB  - Purine nucleoside phosphorylase (PNP) deficiency in humans produces a relatively
      selective depletion of T-cells. Inhibitors of PNP are therefore of interest as
      potential T-cell selective immunosuppressive agents. BCX-1777 is a potent
      inhibitor of PNP and in vitro T-cell proliferation. Inhibition of human T-cells
      by BCX-1777 and deoxyguanosine (dGuo) is accompanied by deoxyguanosine
      triphosphate (dGTP) accumulation. Unlike human T-cells, mouse, rat, dog and
      monkey T-cells are neither inhibited (IC50>100 microM) nor accumulate dGTP in the
      presence of BCX-1777 and dGuo. Cells pretreated with BCX-1777 and dGuo for 24 h
      (to elevate dGTP levels) prior to stimulation demonstrated 80% inhibition similar
      to the inhibition observed with cells treated with BCX-1777 and dGuo during the
      stimulation and proliferation process. This further confirms that inhibition of T
      cells is due to the accumulation of dGTP in these cells. Deoxynucleotide (dNTP)
      analysis of the cells treated with BCX-1777 and dGuo for 48 h showed no
      significant change in deoxycytidine triphosphate (dCTP) and deoxyadenosine
      triphosphate (dATP) pools. However, a decrease (2-fold) in thymidine triphosphate
      (dTTP) pools, and a large increase in dGTP pools (15-fold) were observed. Results
      from various groups have shown that alteration in the dNTP supply results in DNA
      fragmentation and cell death with characteristics of apoptosis. Indeed, apoptosis
      is observed in human T-lymphocytes treated with BCX-1777 and dGuo. To compare the
      in vivo efficacy of BCX-1777 with another potent T-cell inhibitor, cyclosporin,
      these drugs were tested in a xenogeneic graft-vs.-host disease model (XGVHD). In
      this model, human lymphocytes are engrafted into severe combined immunodeficient
      mice (SCID) mice inducing severe XGVHD. The efficacy of BCX-1777 in the XGVHD
      model was comparable to cyclosporin and a combination of BCX-1777 and cyclosporin
      treatment showed a trend towards increased efficacy compared to cyclosporin
      alone. These results suggest that BCX-1777 may be useful for the treatment of
      disease characterized by activated T-cell responses.

PMID- 12188034
TI  - Flt3 ligand augmentation of T cell mitogenesis and expansion of type 1
      effector/memory T cells.
AB  - Herein we report mechanisms whereby Flt3 ligand (FL) augments steady state T cell
      activity in addition to the expansion of dendritic cells (DCs). We demonstrate
      that in vivo administration of FL increases the frequency and absolute number of
      effector/memory T cells and preferentially expands T cells that express a type-1
      cytokine phenotype. In addition, FL enhances T cell proliferative responses to
      Concanavalin A that directly correlated with increased frequencies in
      effector/memory T cells and expansion of lymphoid-derived (type 1) DCs (DC1s).
      Together, these data demonstrate that mechanisms of FL-induced T cell regulation
      include not only the expansion of DC subsets, but also the preferential expansion
      of type 1 -effector/memory T cell populations, and suggest multiple mechanisms of
      action for FL as a vaccine adjuvant and as a therapeutic modality.

PMID- 12188035
TI  - Species-specific differences in the glucocorticoid receptor transactivation
      function upon binding with betamethasone-esters.
AB  - Glucocorticoids (GCs) are the most effective drugs for anti-inflammatory
      diseases. A number of adverse side effects, however, limit chronic treatment with
      GCs. To improve their therapeutic usefulness, attempts have been made to
      dissociate the two main actions of the glucocorticoid receptor (GR),
      transactivation and transrepression, which are believed to be responsible for the
      side effects and anti-inflammatory effects, respectively. We report here species
      specific differences in the transactivation response mediated by GR.
      Dexamethasone (DEX), betamethasone (BM), and their esterified-derivatives had
      full transrepression agonistic activity in a reporter assay using CV-1 cells
      transfected with either human or rat GR. These GCs also had full transactivation
      agonistic activity in CV-1 cells transfected with human GR. The esterified-BM,
      however, had only partial transactivation agonistic activity in cells transfected
      with rat GR, whereas BM and esterified-DEX had full transactivation agonistic
      activity. Moreover, in rat hepatoma H4-II-E cells, the esterified-BM failed to
      induce tyrosine aminotransferase, which is regulated by GR-mediated
      transactivation activity. There were no significant differences between the
      binding affinity of these GCs to human and rat GR. Consistent with the weak
      transactivation activity of esterified-BM mediated by rat GR, there were few side
      effects, evaluated by thymus involution and body weight loss, in an antigen
      induced asthmatic model in rats. These results suggest that the potency of
      esterified-BM to induce transactivation activity is different between species and
      that this difference is not due to differences in receptor binding.

PMID- 12188036
TI  - Chronic methamphetamine exposure alters immune function in normal and retrovirus
      infected mice.
AB  - Methamphetamine (MA) abuse represents a growing problem in the USA with an
      increase of sudden death. To evaluate the immune function alterations due to
      chronic methamphetamine use, we examined C57BL/C mice with LP-BM5 retrovirus
      infection plus methamphetamine exposure. Mice were randomly assigned to the
      following groups: placebo, placebo retrovirus-infected, uninfected MA treated and
      retrovirus-infected MA treated. Placebo, MA-treated groups were intraperitoneally
      injected with saline, MA, respectively, with a gradually increasing dose from 15
      to 40 mg/kg for 12 weeks (5 days/week). Con A- and LPS-induced mitogenesis of
      splenocytes, cytokine production by splenocytes culture and lipid peroxides in
      the liver were measured. Heart tissue histopathology was analyzed in all the
      groups with murine cytomegalovirus (CMV) superinfection. Our data showed that MA
      treatment significantly decreased production of IL-2 and interferon gamma (IFN
      gamma) in uninfected mice but did not further suppress the reduced Th1 cytokines
      in retrovirus-infected mice. There were no significant effects on cytokines IL-4
      and IL-6. However, tumor necrosis factor (TNF-alpha) was significantly increased
      in both uninfected and infected mice due to MA treatment. Lipid peroxides in
      liver were significantly increased both in uninfected and retrovirus-infected
      mice due to MA exposure. Vitamin E levels in liver were significantly decreased
      in uninfected mice due to MA treatment. CMV superinfection greatly increased the
      cardiac lesions in retrovirus-infected mice while no significant histopathology
      changes were detected due to MA treatment. Our data suggest that MA has
      immunomodulation activity, suppressing Th1 cytokine production and enhancing some
      Th2 cytokine secretion, as well as increasing lipid peroxides in uninfected mice.
      The interaction between LP-BM5 and MA remains unclear.

PMID- 12188037
TI  - Selective pharmacological inhibitors reveal the role of Syk tyrosine kinase,
      phospholipase C, phosphatidylinositol-3'-kinase, and p38 mitogen-activated
      protein kinase in Fc receptor-mediated signaling of chicken heterophil
      degranulation.
AB  - Fc receptors of avian heterophils play a primary role in the elimination of
      bacterial pathogens in poultry. The cross-linking of Fc receptors with IgG
      bacteria complexes results in the secretion of toxic oxygen metabolites and anti
      bacterial granules. We have been investigating the upstream signaling events that
      precede degranulation following crosslinkage of Fc receptors on heterophils.
      Previously when using the non-selective pharmacological inhibitors genistein,
      chelerythrine, verapamil, and pertussis toxin, we found no significant inhibitory
      effects on Fc-mediated heterophil degranulation. In the present studies, we used
      more selective pharmacological inhibitors to investigate the roles of protein
      tyrosine kinases, phospholipase C (PLC), phosphatidylinositol 3'-kinase, and the
      family of mitogen-activated protein kinases (MAPK) on Fc-mediated heterophil
      degranulation. Inhibitors of the receptor-linked tyrosine kinases (the
      tryphostins AG 1478 and AG 1296) had no attenuating effects on the Fc receptor
      mediated degranulation of chicken heterophils. Likewise, PP2, a selective
      inhibitor of the Src family of protein tyrosine kinases, had no inhibitory
      effects on degranulation. However, piceatannol, a selective inhibitor of Syk
      tyrosine kinase, significantly attenuated the effect of Fc receptor-mediated
      degranulation. Additionally, Fc-mediated degranulation was significantly
      attenuated by SB 203580, an inhibitor of p38 MAPK, but not by PD98059, an
      inhibitor of the extracellular signal-regulated kinase (ERK). An inhibitor of
      phospholipase C, U73122 and LY294002, an inhibitor of phosphoinositol-3 kinase
      significantly decreased heterophil degranulation. These results suggest that the
      Fc receptors on chicken heterophils, like their counterparts on mammalian
      neutrophils, have no intrinsic tyrosine kinase activity, but probably mediate
      downstream events through activation of tyrosine-based activation motifs (ITAM).
      Activation of the Syk tyrosine kinase stimulates downstream phosphorylation of
      p38 MAPK, phospholipase C, and phosphatidylinositol-3 kinase as signaling
      pathways that regulate Fc-receptor-mediated degranulation of chicken heterophils.
      Engaging Fc receptors on chicken heterophils activates a Syk-->PLC-->PI3-K-->p38
      MAPK signal transduction pathway that induces degranulation.

PMID- 12188039
TI  - The immunostatus of natural killer cells in people exposed to sulfur mustard.
AB  - Sulfur mustard (2,2-dichloroethyl sulfide, SM) has been documented as an
      alkylating agent. It has been widely used as a chemical weapon during the last
      two decades. Despite extensive worldwide research, no effective therapy has yet
      been devised for the treatment of patients exposed to SM. A severe suppression of
      the immune system still remains as the major cause of opportunistic infections,
      septicemia and death in such patients. The aim of this study was to determine the
      possible effect of SM on natural killer (NK) cells in patients suffering from SM
      injuries. Patients were classified into three groups: mild, moderate and severe.
      Blood sample obtained from each patient was examined using flowcytometric
      technique. Results showed that the percentage of NK cells (CD45+/CD56+) is
      significantly lower in severe patients than that of the control group (P<0.05).
      It was also observed that the activity of NK cells (CD56+/CD25+) in severe
      alkylating group is noticeably higher compared with the control group (P<0.1).

PMID- 12188038
TI  - The kappa-opioid agonist U-69593 affects intracellular calcium level in R1.1
      mouse thymoma cell line.
AB  - In this study, the effect of the kappa-opioid agonist U-69593 on the
      intracellular calcium level in R1.1. cells was investigated using FURA 2-AM dye.
      In the previous study, calcium transport into R1.1 cells was not affected by the
      kappa-opioid agonist (-)U50,488 [Int. J. Immunopharmacol. 21 (1999) 133]. In this
      study, the kappa-opioid agonist U-69593 (10(-10)-10(-6) M), decreased
      intracellular calcium level in unstimulated cells. This decrease could not be
      reversed by the kappa-opioid antagonist NBI (10(-5) or 10(-6) M). Ionophore
      A23187 was used to increase intracellular calcium level. Stimulation of
      intracellular calcium level by Ionophore A23187 was potentiated by the kappa
      opioid agonist U-69593. Thus, we have shown that basal intracellular calcium
      level was decreased in R1.1 by the kappa-opioid agonist U-69593 and increased in
      R1.1 cells stimulated by Ionophore A23187.

PMID- 12188040
TI  - Immunomodulation by ethanolic extract of Boerhaavia diffusa roots.
AB  - We have earlier reported that ethanolic extract of Boerhaavia diffusa, a plant
      used in Indian traditional system of medicine, significantly inhibits the cell
      proliferation. This led us to evaluate the immunomodulatory properties of this
      plant extract on various in vitro tests such as human natural killer (NK) cell
      cytotoxicity, production of nitric oxide (NO) in mouse macrophage cells, RAW
      264.7, interleukin-2 (IL-2), tumor necrosis factor-alpha (TNF-alpha),
      intracytoplasmic interferon-gamma (IFN-gamma) and expression of various cell
      surface markers on human peripheral blood mononuclear cells (PBMCs). Ethanolic
      extracts of B. diffusa roots inhibited human NK cell cytotoxicity in vitro,
      production of NO in mouse macrophage cells, IL-2 and TNF-alpha in human PBMCs.
      Intracytoplasmic IFN-gamma and cell surface markers such as CD16, CD25, and HLA
      DR did not get affected on treatment with B. diffusa extract. Our study
      demonstrates immunosuppressive potential of ethanolic extract of B. diffusa.

PMID- 12188041
TI  - Anti-inflammatory activity of an extract of Petasites hybridus in allergic
      rhinitis.
AB  - Previous studies have suggested that histamine and leukotrienes (LTs) play an
      important pathobiological role in IgE-mediated allergic diseases. In vitro
      studies suggested that an extract of Petasites hybridus (Ze339) blocks LT
      synthesis in monocytes and granulocytes. Petasins are considered to be the
      pharmacologically active fraction within Ze339. Patients suffering from allergic
      rhinitis received three times a day two tablets of Ze339 standardized to 8 mg
      petasins within a time period of 1 week. After 5 days of treatment, Ze339
      significantly improved primary end points, which were day- and nighttime nasal
      symptoms. Nasal resistance, which was measured by rhinomanometry, gradually
      decreased as a consequence of Ze339 treatment reaching normal levels after 5 days
      (rhinomanometry: from 403.5+/-62.0 to 844.8+/-38.8 ml). Levels of inflammatory
      mediators in nasal fluids and serum were measured 90 min after drug
      administration every day in the morning. After 5 days of treatment, a significant
      reduction of histamine (from 153.7+/-32.1 to 53.0+/-8.4 pg/ml) and LT levels
      (LTB4: from 313.1+/-46.5 to 180.6+/-32.2 pg/ml; cysteinyl-LT: from 137.0+/-42.2
      to 70.1+/-16.5 pg/ml) could be observed. Moreover, quality-of-life scores
      significantly improved. The drug had no effect on the distribution of lymphocyte
      subpopulations in the blood as well as on the capacity of blood leukocytes to
      generate cytokines and lipid mediators. These results suggest that Ze339 is
      effective in treating allergic rhinitis patients by decreasing levels of nasal
      inflammatory mediators.

PMID- 12188042
TI  - Genome deterioration: loss of repeated sequences and accumulation of junk DNA.
AB  - A global survey of microbial genomes reveals a correlation between genome size,
      repeat content and lifestyle. Free-living bacteria have large genomes with a high
      content of repeated sequences and self-propagating DNA, such as transposons and
      bacteriophages. In contrast, obligate intracellular bacteria have small genomes
      with a low content of repeated sequences and no or few genetic parasites. In
      extreme cases, such as in the 650 kb-genomes of aphid endosymbionts of the genus
      Buchnera all repeated sequences above 200bp have been eliminated. We speculate
      that the initial downsizing of the genomes of obligate symbionts and parasites
      occurred by homologous recombination at repeated genes, leading to the loss of
      large blocks of DNA as well as to the consumption of repeated sequences. Further
      sequence elimination in these small genomes seems primarily to result from the
      accumulation of short deletions within genic sequences. This process may lead to
      temporary increases in the genomic content of pseudogenes and 'junk' DNA. We
      discuss causes and long-term consequences of extreme genome size reductions in
      obligate intracellular bacteria.

PMID- 12188043
TI  - Why so many noncoding nucleotides? The eukaryote genome as an epigenetic machine.
AB  - It is recalled that dispensability of sequences and neutral substitution rate
      must not be construed to be markers of nonfunctionality. Different aspects of
      functionality relate to differently-sized nucleotide communities. At the time
      cells became nucleated, a boom of epigenetic processes led to uses of DNA that
      required many more nucleotides operating collectively than do functions definable
      in terms of classical genetics. Each order of magnitude of nucleotide plurality
      was colonized by functions germane to that order. The eukaryote genome became a
      great epigenetic machine. Sequences of different levels of nucleotide plurality
      are briefly discussed from the point of view of their functional relevance. By
      their activities as both transcribed genes and cis-acting repeats, SINEs and
      LINEs are the principal link between genetic and epigenetic processes. SINEs can
      act as local repeats to produce position effect variegation (PEV) in a nearby
      gene. PEV may thus represent a general method of overall transcriptional
      regulation at the level of cell collectivities. When tracking the scale
      dependence of nucleotide function, one finds the 100 kb order of nucleotide
      plurality to provide epigenetically the basis at once for PEV, imprinting, and
      cell determination, with sectorial repressibility a trait common to the three. In
      sectorial repressibility, introns may play a structural role favoring the
      stability of higher-order chromatin structures. At that level of nucleotide
      involvement, nonconserved nonhomologous nonprotein-coding sequences may often
      play the same structural roles. In addition, genomic distance per se--and,
      therefore, the mass of intervening nucleotides--can have functional effects.
      Distances between enhancers and promoters need to be probed in this respect. At
      the 1,000 kb level of nucleotide function, attention is focused on the formation
      of centromeres. It is one of the levels of nucleotide plurality per function
      where specificity in the generation of DNA/protein complexes seems to depend more
      upon the structural fit among factors than upon the DNA sequence. This
      circumstance may explain in part the prevailing difficulty in recognizing the
      functional nature of sequences among non-protein-coding nucleotide arrays and the
      propensity among investigators to tag the majority of DNA sequences in higher
      organisms as functionally meaningless. Noncoding DNA often may not be 'selected'
      as an appropriate niche for a certain function, but be 'elected' in that capacity
      by a group of factors, as a preexisting sequence that is only now called upon to
      serve. Much of the non-protein-coding DNA may thus be only conditionally
      functional and in fact may never be elected to functions at a high level of
      nucleotide plurality. Eukaryotes are composites, at different levels of this
      plurality, of the functional and the nonfunctional, as well as of the
      conditionally functional and the outright functional. Thus, a sequence that is
      nonfunctional at one level of nucleotide plurality may participate in a
      functional sequence at a more inclusive level. In the end, every nucleotide is at
      least infinitesimally functional if, for metabolic and developmental reasons, the
      chromatin mass as such becomes a selectable entity. Given the scale dependence of
      nucleotide function, large amounts of 'junk DNA', contrary to common belief, must
      be assumed to contribute to the complexity of gene interaction systems and of
      organisms.

PMID- 12188044
TI  - Jam packed genomes--a preliminary, comparative analysis of nucleomorphs.
AB  - There are two ways eukaryotic cells can permanently acquire chloroplasts. They
      can take up a cyanobacterium and turn it into a chloroplast or they can engulf an
      alga that already has a chloroplast. The second method is far more common and
      there are at least seven major groups of protists that have obtained their
      chloroplasts, this way. In most cases little remains of the engulfed alga apart
      from its chloroplast, but in two groups, the cryptomonads and
      chlorarachniophytes, a small remnant nucleus of the engulfed alga is still
      present. These tiny nuclei, called nucleomorphs, are the smallest and most
      compact eukaryotic genomes known and recently the nucleomorph of the cryptomonad
      alga Guillardia theta, was completely sequenced (551 kilobases). The nucleomorph
      of the chlorarachniophyte Bigellowiella natans (380 kilobases), is also being
      sequenced and is about half complete. We discuss some of the similarities and
      differences that are emerging between these two nucleomorph genomes. Both genomes
      contain just three chromosomes that encode mainly housekeeping genes and a few
      proteins for chloroplast functions. The bulk of nucleomorph gene coding capacity,
      therefore, appears to be devoted to self perpetuation and creating gene and
      protein expression machineries to make a small number of essential chloroplast
      proteins. We discuss reasons why both nucleomorphs are extraordinarily compact
      and why their gene sequences are evolving rapidly.

PMID- 12188045
TI  - Genome size and developmental complexity.
AB  - Haploid genome size (C-value) is correlated positively with cell size, and
      negatively with cell division rate, in a variety of taxa. Because these
      associations are causative, genome size has the potential to impact (and in turn,
      be influenced by) organism-level characters affected by variation in either of
      these cell-level parameters. One such organismal feature is development.
      Developmental rate, in particular, has been associated with genome size in
      numerous plant, vertebrate, and invertebrate groups. However, rate is only one
      side of the developmental coin; the other important component is complexity. When
      developmental complexity is held essentially constant, as among many plants,
      developmental rate is the visibly relevant parameter. In this case, genome size
      can impose thresholds on developmental lifestyle (and vice versa), as among
      annual versus perennial plants. When developmental rate is constrained (as during
      time-limited amphibian metamorphosis), complexity becomes the notable variable.
      An appreciation for this rate-complexity interaction has so far been lacking, but
      is essential for an understanding of the relationships between genome size and
      development. Moreover, such an expanded view may help to explain patterns of
      variation in taxa as diverse as insects and fish. In each case, a hierarchical
      approach is necessary which recognizes the complex interaction of evolutionary
      processes operating at several levels of biological organization.

PMID- 12188046
TI  - Mechanisms and rates of genome expansion and contraction in flowering plants.
AB  - Plant genomes are exceptional for their great variation in genome size, an
      outcome derived primarily from their frequent polyploid origins and from the
      amplification of retrotransposons. Although most studies of plant genome size
      variation have focused on developmental or physiological effects of nuclear DNA
      content that might influence plant fitness, more recent studies have begun to
      investigate possible mechanisms for plant genome expansion and contraction.
      Analyses of 'relatively neutral' genome components, like transposable elements,
      have been particularly fruitful, largely due to the enormous growth in genomic
      sequence information from many different plant species. Current data suggest that
      unequal recombination can slow the growth in genome size caused by
      retrotransposon amplification, but that illegitimate recombination and other
      deletion processes may be primarily responsible for the removal of non-essential
      DNA from small genome plants.

PMID- 12188047
TI  - Feast and famine in plant genomes.
AB  - Plant genomes vary over several orders of magnitude in size, even among closely
      related species, yet the origin, genesis and significance of this variation are
      not clear. Because DNA content varies over a sevenfold range among diploid
      species in the cotton genus (Gossypium) and its allies, this group offers
      opportunities for exploring patterns and mechanisms of genome size evolution. For
      example, the question has been raised whether plant genomes have a 'one-way
      ticket to genomic obesity', as a consequence of retroelement accumulation. Few
      empirical studies directly address this possibility, although it is consistent
      with recent insights gleaned from evolutionary genomic investigations. We used a
      phylogenetic approach to evaluate the directionality of genome size evolution
      among Gossypium species and their relatives in the cotton tribe (Gossypieae,
      Malvaceae). Our results suggest that both DNA content increase and decrease have
      occurred repeatedly during evolution. In contrast to a model of unidirectional
      genome size change, the frequency of inferred genome size contraction exceeded
      that of expansion. In conjunction with other evidence, this finding highlights
      the dynamic nature of plant genome size evolution, and suggests that poorly
      understood genomic contraction mechanisms operate on a more extensive scale that
      previously recognized. Moreover, the research sets the stage for fine-scale
      analysis of the evolutionary dynamics and directionality of change for the full
      spectrum of genomic constituents.

PMID- 12188048
TI  - Transposable elements and the evolution of genome size in eukaryotes.
AB  - It is generally accepted that the wide variation in genome size observed among
      eukaryotic species is more closely correlated with the amount of repetitive DNA
      than with the number of coding genes. Major types of repetitive DNA include
      transposable elements, satellite DNAs, simple sequences and tandem repeats, but
      reliable estimates of the relative contributions of these various types to total
      genome size have been hard to obtain. With the advent of genome sequencing, such
      information is starting to become available, but no firm conclusions can yet be
      made from the limited data currently available. Here, the ways in which
      transposable elements contribute both directly and indirectly to genome size
      variation are explored. Limited evidence is provided to support the existence of
      an approximately linear relationship between total transposable element DNA and
      genome size. Copy numbers per family are low and globally constrained in small
      genomes, but vary widely in large genomes. Thus, the partial release of
      transposable element copy number constraints appears to be a major characteristic
      of large genomes.

PMID- 12188049
TI  - Expansion of genome coding regions by acquisition of new genes.
AB  - As it is the case for non-coding regions, the coding regions of organisms can be
      expanded or shrunk during evolutionary processes. However, the dynamics of coding
      regions are expected to be more correlated with functional complexity and
      diversity than are the dynamics of non-coding regions. Hence, it is interesting
      to investigate the increase of diversity in coding regions--the origin and
      evolution of new genes - because this provides a new component to the genetic
      variation underlying the diversity of living organisms. Here, we examine what is
      known about the mechanisms responsible for the increase in gene number. Every
      mechanism affects genomes in a distinct way and to a different extent and it
      appears that certain organisms favor particular mechanisms. The detail of some
      interesting gene acquisitions reveals the extreme dynamism of genomes. Finally,
      we discuss what is known about the fate of new genes and conclude that many of
      the acquisitions are likely to have been driven by natural selection; they
      increase functional complexity, diversity, and/or adaptation of species. Despite
      this, the correlation between complexity of life and gene number is low and
      closely related species (with very similar life histories) can have very
      different number of genes. We call this phenomenon the G-value paradox.

PMID- 12188050
TI  - DNA loss and evolution of genome size in Drosophila.
AB  - Mutation is often said to be random. Although it must be true that mutation is
      ignorant about the adaptive needs of the organism and thus is random relative to
      them as a rule, mutation is not truly random in other respects. Nucleotide
      substitutions, deletions, insertions, inversions, duplications and other types of
      mutation occur at different rates and are effected by different mechanisms.
      Moreover the rates of different mutations vary from organism to organism.
      Differences in mutational biases, along with natural selection, could impact gene
      and genome evolution in important ways. For instance, several recent studies have
      suggested that differences in insertion/deletion biases lead to profound
      differences in the rate of DNA loss in animals and that this difference per se
      can lead to significant changes in genome size. In particular, Drosophila
      melanogaster appears to have a very high rate of deletions and the
      correspondingly high rate of DNA loss and a very compact genome. To assess the
      validity of these studies we must first assess the validity of the measurements
      of indel biases themselves. Here I demonstrate the robustness of indel bias
      measurements in Drosophila, by comparing indel patterns in different types of
      nonfunctional sequences. The indel pattern and the high rate of DNA loss appears
      to be shared by all known nonfunctional sequences, both euchromatic and
      heterochromatic, transposable and non-transposable, repetitive and unique.
      Unfortunately all available nonfunctional sequences are untranscribed and thus
      effects of transcription on indel bias cannot be assessed. I also discuss in
      detail why it is unlikely that natural selection for or against DNA loss
      significantly affects current estimates of indel biases.

PMID- 12188051
TI  - Genome size and the accumulation of simple sequence repeats: implications of new
      data from genome sequencing projects.
AB  - The relationship between the level of repetitiveness in genomic sequences and
      genome size has been re-investigated making use of the rapidly growing database
      of complete eubacterial and archaeal genome sequences combined with the
      fragmentary but now large amount of data from eukaryotic genomes. Relative
      simplicity factors (RSFs), which measure the repetitiveness of sequences, were
      calculated and significantly simple motifs (SSMs), which identify the kinds of
      sequences that are repeated, were identified. A previously reported correlation
      between genome size and repetitiveness was confirmed, but it was shown that the
      higher RSFs seen in eukaryotic genomes also reflect a generally higher level of
      repetitiveness independent of genome size differences. Differences in genome size
      are responsible for about 10% of the variance in RSF seen between species. The
      spectrum of SSMs seen within a genome differed markedly within the eubacteria but
      less so in eukaryotes and, particularly, in archaea. Species with SSM spectra
      that differ from the norm tend also to have high RSFs for their genome size and
      to be pathogens that make use of repetitive sequences to avoid host defence
      responses. Some of the variance in repetitiveness seen in other species may
      therefore also reflect the action of selection, although other forces such as
      variation in the effectiveness of mechanisms for regulating slippage errors of
      replication, may also be important.

PMID- 12188052
TI  - Acculturation and adaptation of Soviet Jewish refugee adolescents: predictors of
      adjustment across life domains.
AB  - This study explores how acculturation is related to adaptation across different
      life spheres for 162 Soviet Jewish refugee adolescents in a suburban community in
      Maryland. Because the different contexts of refugee adolescents' lives vary in
      acculturative demands, different patterns of acculturation should be related to
      adaptation in different life spheres. The study uses a multidimensional measure
      of acculturation and assesses acculturation to both American and Russian cultures
      as it relates to psychological adaptation, peer relations, and school and family
      outcomes. Findings support the general ecological thesis that acculturation to
      different cultures is differentially related to adaptation across life domains.
      Acculturation to American culture predicted better grades and perceived support
      from American peers. Acculturation to Russian culture predicted perceived support
      from Russian peers. Both American acculturation and Russian acculturation
      predicted reduced loneliness and perceived support from parents. Further,
      different dimensions of acculturation, such as language and identity, were
      differentially related to adaptation. Implications for acculturation theory and
      measurement are drawn, and cautions are offered about the interpretation of
      acculturation studies using single proxies such as language use or preference.

PMID- 12188053
TI  - Beyond bruises and broken bones: the joint effects of stress and injuries on
      battered women's health.
AB  - We investigated the joint mediating effects of injuries and stress on the
      relationship between abuse and women's health. A community sample of 397 women,
      half of whom had been assaulted by an intimate partner within the prior 6 months,
      was interviewed about their experience of intimate partner violence, injuries,
      stress, income, depression, and physical health problems. Structural equation
      modeling techniques confirmed the complex model of hypothesized indirect effects
      of abuse on women's physical health problems through injuries, stress, and
      depression. Stress accounted for 80% of the indirect effect of abuse on women's
      physical health. Its direct effect on physical health was somewhat larger than
      its indirect effect through depression, but both processes played a key role in
      determining the effect of abuse on women's physical health problems. Furthermore,
      abuse was a stronger predictor of women's stress than was poverty. Implication
      and future research are discussed.

PMID- 12188054
TI  - Do Internet-based support interventions change perceptions of social support?: An
      experimental trial of approaches for supporting diabetes self-management.
AB  - Internet-based support groups are a rapidly growing segment of mutual aid
      programs for individuals with chronic illnesses and other challenges. Previous
      studies have informed us about the content of online exchanges between support
      group members, but we know little about the ability of these interventions to
      change participants' perceptions of support. A randomized trial of 160 adult Type
      2 diabetes patients provided novice Internet users with computers and Internet
      access to 1 of 4 conditions: (a) diabetes information only, (b) a personal self
      management coach, (c) a social support intervention, or (d) a personal self
      management coach and the support intervention. After 3 months, individuals in the
      2 support conditions reported significant increases in support on a diabetes
      specific support measure and a general support scale. Participants' age was
      significantly related to change in social support, but intervention effects were
      still significant after accounting for this relationship. This report is a
      critical first step in evaluating the long-term effects of Internet-based support
      for diabetes self-management. The discussion identifies directions for future
      research.

PMID- 12188055
TI  - Gender, economic context, perceptions of safety, and quality of life: a case
      study of Lowell, Massachusetts (U.S.A.), 1982-96.
AB  - From 1982 through 1996, 840 structured interviews about urban quality of life
      (QOL) were conducted with residents of Lowell, Massachusetts, by graduate
      students in a seminar about the city. Perceptions of safety and general QOL were
      analyzed by social status (gender) and social contexts (economic and historic)
      using multivariate and univariate ANOVAS. Main effects were obtained for gender,
      area income, and time. Subsequent analyses revealed that men felt safer than did
      women at night in neighborhoods and downtown, and that residents of lower income
      areas perceived both neighborhood QOL and safety more negatively than residents
      of higher income areas did. Small effects were found for downtown safety by area
      income in the opposite direction. Differences over time for downtown safety and
      city QOL (but not for neighborhood) suggest that the early and mid-1980s were
      viewed somewhat more favorably than the 1990s, with some improvement in the most
      recent period. Results suggest that economic context and time were related to
      perceived safety and QOL, though in different ways, whereas gender was related to
      perceived safety but not to QOL. Respondents' comments and community psychology
      principles are used to elaborate on and suggest interpretations for quantitative
      results.

PMID- 12188056
TI  - The adoption of innovation in collective action organizations.
AB  - This study used a quantitative/qualitative methodology to explore how collective
      action organizations (CAOs) remain open to organizational change and innovation.
      It examined the adoption of inclusion--a recent innovation in the field of
      disabilities--by local chapters of The Arc Michigan (a disabilities CAO). We
      found considerable variability in the adoption of inclusion by local Arc
      chapters. This variability was significantly related to the ecology surrounding
      these chapters. Local Arc chapters that had adopted an inclusion philosophy had
      significantly different internal and external environments from those that had
      not adopted inclusion. Our qualitative findings make it clear, however, that
      innovative Arc chapters were not the passive recipients of these internal and
      external influences. These chapters were proactive players in defining and
      shaping the nature of their internal and external environments. Strategies that
      were related to a chapter's ability to remain open to innovation included (a) a
      change orientation, (b) a conscious philosophy or vision, (c) a proactive
      strategy for achieving chapter goals and overcoming barriers to change, (d) the
      creation of a supportive organizational network, and (e) avoidance of resource
      dependencies that required them to engage in activities that were inconsistent
      with the innovation. These findings provide a framework by which CAOs can
      maintain an openness to innovation and remain on the forefront of social change.

PMID- 12188057
TI  - Mother-child separations among homeless and housed families receiving public
      assistance in New York City.
AB  - We examined the incidence, characteristics, and predictors of separations of
      children from mothers in 543 poor families receiving public assistance, 251 of
      whom had experienced homelessness during the previous 5 years. Forty-four percent
      of the homeless mothers and 8% of housed mothers were separated from one or more
      children. A total of 249 children were separated from 110 homeless families and
      34 children from 23 housed families. Children were placed with relatives and in
      foster care but were rarely returned to their mothers. Maternal drug dependence,
      domestic violence, and institutionalization predicted separations, but
      homelessness was the most important predictor, equivalent in size to 1.9 other
      risk factors. We infer that policies regarding child welfare and substance abuse
      treatment should be changed to reduce unnecessary placements. Studies of homeless
      children who remain with families may be biased if separated children are
      excluded.

PMID- 12188058
TI  - A multiple case study of rape victim advocates' self-care routines: the influence
      of organizational context.
AB  - This study assumes that rape victim advocates who provide community outreach
      services to victimized women must adjust to a heightened awareness of sexual
      violence to do their jobs. Using qualitative methodology, this multiple case
      study explored rape victim advocates' strategies for incorporating repeated
      exposure to sexual assault into their daily lives as well as ways that
      organizations can support such endeavors. Findings suggest that advocates' self
      care routines draw upon various personal resources (i.e., cognitive, physical,
      social, spiritual, verbal), and serve 2 roles for coping with rape-related pain:
      (a) cathartic releasing of traumatic material, and (b) improving capacity to
      integrate the traumatic material into one's life. Additionally, over 20
      organizational characteristics that workers perceive to be supportive (e.g.,
      weekly meetings, flexible hours) were identified. Nonparametric and categorical
      statistical analyses were used to analyze the relationship between organizational
      support and self-care routines, finding that advocates working in organizations
      with higher levels of support utilize more strategies that are integrative in
      nature. Implications of these findings are discussed.

PMID- 12188059
TI  - Tuberculosis--barriers to early diagnosis.

PMID- 12188060
TI  - Tuberculosis--are we missing the diagnosis?
AB  - We reviewed the 52 new cases of pulmonary tuberculosis diagnosed at Pusat Pakar
      Utara, Kedah in 1998. It was found that the majority of the patients had symptoms
      for many years. They had seen many doctors but were not diagnosed. In 40% of the
      patients, no investigations for tuberculosis were done and in the others
      tuberculosis was excluded because of negative sputum smear examination. Many had
      typical history and X-ray changes suggestive of tuberculosis but more sensitive
      investigations such as sputum culture for Mycobacterium or bronchoscopy were not
      performed. Cases are presented to illustrate the problems in the diagnosis.

PMID- 12188061
TI  - The impact of minimal access surgery on gynaecological surgery in a university
      gynaecological unit over a 10-year period from 1991 to 2000.
AB  - OBJECTIVE: To assess the impact of minimal access surgery in replacing
      traditional open approach of surgery for benign gynaecological pathology.
      SETTING: Gynaecological unit in a university hospital. METHODOLOGY: All surgical
      procedures for the treatment of ectopic pregnancy, benign ovarian cyst,
      myomectomy, and hysterectomy for benign gynaecological pathology over a 10-year
      period (1991 to 2000) were studied. The percentages of procedures performed with
      the minimal access approach were compared with the traditional open approach over
      the study period. FINDINGS: The percentage of ectopic pregnancies treated
      laparoscopically has increased from a low of 27% in the initial two-year period
      of 1991-92 to stabilise at approximately 70% at the end of the decade.
      Laparoscopic approach for the treatment of benign ovarian cysts constituted just
      31% of cases in the initial period (1991-92) and rose steadily to stabilise at
      approximately 50% of cases during the last four years of the decade. The
      proportion of advanced minimal access procedures such as myomectomy and
      hysterectomy increased at a more gradual pace during the decade. By 1999-2000,
      laparoscopic and hysteroscopic myomectomy constituted about 30% of all
      myomectomies but laparoscopic hysterectomy accounted for just about 5% of all
      hysterectomies performed. CONCLUSIONS: Minimal access surgery has largely
      replaced the open approach for the treatment of ectopic pregnancy and benign
      ovarian cysts. Advanced minimal access procedures such as myomectomy and
      hysterectomy showed a rising trend through the decade, but still accounted for a
      minority of procedures at the end of the decade.

PMID- 12188062
TI  - Intracranial germ cell tumour: experience of a Singaporean institution over 11
      year period.
AB  - BACKGROUND: Intracranial germ cell tumours (IGCT) are rare. We present our
      experience in Therapeutic Radiology Department, National Cancer Centre,
      Singapore. METHODS: A retrospective study was conducted through case notes review
      on 25 patients with IGCT referred between January 1988 and January 1999. RESULTS:
      The median age at diagnosis was 13 years (range 6-22). The tumours were mainly
      pineal germinoma (72%). Median follow-up for living patients was 2.57 years
      (range 0.12-10.8). Median radiotherapy (RT) dose to whole brain, primary site and
      spine was 35.3,54 and 30 Gys respectively. Four to six cycles of BEP or JEB
      chemotherapy (CM) were given in 10 patients. As for the whole study group, the
      seven-year overall survival (OS) and recurrence-free survival (RFS) were 86% (95%
      CI 72-100) and 78% (95% CI 60-100) respectively. The 10-year OS and RFS were 65%
      (95% CI 36-100) and 78% (95% CI 60-100) respectively. The germinoma group had 75%
      10-year OS and 86% 10-year RFS. Mixed germinoma and non-germinoma germ cell
      tumours (NGGCT) group had 50% one-year RFS and 44% two-year OS. Acute side
      effects of RT and CM were minimal. There was no statistically significant
      difference in side-effects when treatment modalities were compared. CONCLUSION:
      In the treatment of intracranial germinoma, we recommend biopsy and CSRT. Primary
      chemotherapy (+/- low-dose cranial RT) should be used in the protocol or clinical
      trial settings. Chemo-radiotherapy is recommended for mixed germinoma and NGGCT.
      A multicentre trial is needed to address various controversial issues.

PMID- 12188063
TI  - Prevalence of prostatitis-like symptoms in Singapore: a population-based study.
AB  - OBJECTIVE: To study the prevalence of prostatitis-like symptoms in a generally
      healthy population. SUBJECTS AND METHODS: A population-based cross-sectional
      survey was conducted in Singapore to evaluate "prostatitis-like symptoms" (PS),
      lower urinary tract symptoms (LUTS),erectile dysfunction (ED), and quality of
      life (QoL). Respondents with pain or discomfort in the perineum, testicles, tip
      of penis or bladder/suprapubic region were identified as having prostatitis-like
      symptoms. RESULTS: Altogether, 1087 males aged 21 to 70 were evaluated. While at
      least 20% of them had some degree of LUTS, only 2.67% (29 out of 1087) had pain
      or discomfort suggestive of prostatitis. Six men had pain in the bladder or
      suprapubic region, two in the perineum, six at the tip of penis and 26 had pain
      during micturition (11 subjects had more than one location of pain). Only two men
      had severe pain while seven had moderate and the rest had mild pain. The mean age
      of subjects with PS was 43.14. In terms of racial distribution, 2.23% (18) of
      Chinese, 3.15% (4) of Malay, 4.49% (4) of Indians and 12.12% (3) of other ethnic
      origin had PS. Those who had PS had worse erectile function (International Index
      of Erectile Function (IIEF) 11.92 vs. 17.16, p < 0.003) and a worse QoL score
      (2.96 vs. 1.38, p < 0.001) than those without PS. Those with PS were more
      bothered and worried about their symptoms. CONCLUSION: The prevalence of
      prostatitis-like symptoms in a largely Chinese population is 2.67%. Prostatitis
      like symptoms have a negative impact on the quality of life and erectile
      function.

PMID- 12188064
TI  - Mutation analysis of the BRCA1 gene in Malaysian breast cancer patients.
AB  - Thirty patients with early onset breast cancer or familial breast cancer from
      Malaysia were analysed for germline mutation in the early onset breast cancer I
      gene (BRCA1). Direct sequencing of the entire coding region of BRCA1 identified a
      frameshift mutation, c.5447-5448insC (insC5447) (codon 1776 of exon 21) in a
      patient aged 32 of the Malay ethnic origin, who had no family history of breast
      and/or ovarian cancer. Eight polymorphisms (2201C > T, 2430T > C, P871L, E1038G,
      K1183R, 4427T > C, S1613G and IVS8-57delT) were identified in the samples tested.

PMID- 12188065
TI  - Stroke prevention in elderly patients with atrial fibrillation.
AB  - BACKGROUND: The prevalence of atrial fibrillation increases with age. Atrial
      fibrillation has been shown to be a significant risk factor for stroke in the
      elderly. Anticoagulation is effective in preventing stroke in geriatric patients
      with atrial fibrillation, yet many elderly patients with atrial fibrillation are
      not anticoagulated. OBJECTIVES: This study aims to determine the prevalence of
      atrial fibrillation in an inpatient population of a geriatric unit and explores
      the usage of anticoagulants in those patients diagnosed with atrial fibrillation.
      METHODS: Consecutive admissions to a geriatric unit were screened with an
      electrocardiogram to establish a diagnosis of atrial fibrillation. Those with
      atrial fibrillation were evaluated for risk factors for stroke and for
      contraindications for anticoagulation. Documentation of reasons for withholding
      anticoagulation was also examined. RESULTS: Five hundred and six consecutive
      inpatient admissions were screened. Fifty-six patients had atrial fibrillation
      (11.1%). Forty of these were known cases of atrial fibrillation whereas sixteen
      were newly diagnosed. There were 22 (39.3%) males and 34 (60.7%) females. The
      mean age was 83.3 years (S.D. 6.8). The four most common risk concomitant factors
      for stroke were age above 75 years (54, 96.4%), hypertension (41, 73.2%),
      congestive cardiac failure (28, 50%), and a history of strokes (20, 35.7%). Fifty
      five (98.2%) patients had at least two other concomitant risk factors for stroke.
      On discharge, only nine (16.1%) out of 56 patients were anticoagulated.
      Anticoagulation was withheld because of contraindications in 44 (78.6%) patients
      and because of patients' objection to anticoagulation in 3 (5.3%) patients. The
      two most common reasons for withholding anticoagulation were the risk of
      recurrent falls (18, 38.3%) and peptic ulcer disease (15, 31.9%). CONCLUSIONS:
      The prevalence rate of atrial fibrillation in elderly inpatients was found to be
      11.1%. Most of the elderly with atrial fibrillation had multiple concomitant risk
      factors for stroke and would benefit from anticoagulant therapy. However, in the
      majority, anticoagulation was withheld because of contraindications (78.6%) and
      patients' objection to anticoagulation (5.3%).

PMID- 12188066
TI  - A case of uterine artery pseudoaneurysms.
AB  - Uterine artery pseudoaneurysms is a rare cause of haemorrhage but is potentially
      life-threatening and can occur after common gynaecological operations such as a
      Caesarean section or a hysterectomy. A 33-year-old woman who developed secondary
      postpartum haemorrhage after a Caesarean section was diagnosed to have uterine
      artery pseudoaneurysms on ultrasound scan. She was treated with bilateral uterine
      artery embolisation via selective catherisation of uterine arteries. Good outcome
      with the aneurysms remaining obliterated was obtained. Angiographic embolisation
      is a safe and effective method of treating postpartum haemorrhage in
      haemodynamically stable patients and should be an option before resorting to
      surgery in appropriately selected cases.

PMID- 12188067
TI  - Management of pathological fracture neck of the femur following recent
      osteomyelitis in a child.
AB  - Fracture neck of the femur is rare in children and occurs following severe
      trauma. Several recommendations have been made for the treatment of displaced
      transcervical fracture type 11 (Delbet classification). However there are no
      recommendations when such a fracture occurs after recent acute osteomyelits of
      the neck of the femur. The management of a case is described with the outcome
      after 36 months.

PMID- 12188068
TI  - Juvenile angiofibroma: case report and the role of endoscopic resection.
AB  - Juvenile angiofibroma is benign yet aggressive. Due to its inaccessible location
      in the nasopharynx, open surgery usually requires osteotomies which cause
      stunting of facial growth in adolescent males. Advances in imaging and treatment
      techniques have now facilitated more accurate staging of this disease. For small,
      extracranial tumours limited to the nasal cavity and paranasal sinus, endoscopic
      resection is a viable alternative. This case report will illustrate how
      endoscopic resection allows good control with minimal morbidity compared to open
      surgery or radiotherapy.

PMID- 12188069
TI  - Clinics in diagnostic imaging (72). Superior labral anterior-posterior (SLAP)
      tear.
AB  - The lesions at and around the superior glenolabral junction of the shoulder have
      gained considerable attention since its description in 1990. A 31-year-old
      Chinese woman with a superior labral anterior-posterior (SLAP) tear is reported.
      The MR arthrogram findings were confirmed at surgery. The classification and
      mechanisms of SLAP lesions, and the role of MR arthrography in the diagnosis of
      glenolabral lesions are discussed.

PMID- 12188070
TI  - The case for breast cancer screening in Singapore.

PMID- 12188071
TI  - Sun Si Miao (581- 682a.d.): China's pre-eminent physician.

PMID- 12188072
TI  - A comparative study of modified radical mastectomy using harmonic scalpel and
      electrocautery.
AB  - AIM: The harmonic scalpel is recently emerging as an alternative surgical tool
      for dissection and haemostasis and has been extensively used in the field of
      minimally invasive surgery. We studied the utility and advantages of this
      instrument over electrocautery for performing modified radical mastectomy.
      METHODS: The operative and morbidity details of twenty-three breast cancer
      patients who underwent modified radical mastectomy using the harmonic scalpel
      were compared with 23 matched controls operated with electrocautery by the same
      surgical team. RESULTS: There was no significant difference in the operating time
      between the harmonic scalpel and electrocautery group (104 and 100 mins, p >
      0.05). The blood loss (60 +/- 35 ml and 294 +/- 155, p < 0.001) and drainage
      volume (590 +/- 430 ml and 1,085 +/- 690 ml, p < 0.001) were significantly lower
      in the harmonic scalpel group. There was a significant reduction of drain days in
      harmonic scalpel group (mean five and nine days, p < 0.05). There was no
      significant difference in the seroma rate between two groups (16% and 22%).
      CONCLUSION: Modified radical mastectomy using harmonic scalpel is feasible and
      learning curve is short. Harmonic scalpel significantly reduces the blood loss
      and duration of drainage as compared to electrocautery.

PMID- 12188073
TI  - Evaluation of the contralateral breast in patients with ipsilateral breast
      carcinoma: the role of mammography.
AB  - OBJECTIVE: To assess the value of mammography in the detection of cancer in the
      contralateral breast in women with ipsilateral breast carcinoma. MATERIALS AND
      METHODS: From February 1994 through May 2001, a total of 500 patients with
      unilateral mastectomy from breast carcinoma had mammograms performed for the
      first time following mastectomy. We retrospectively reviewed the clinical
      findings and mammograms of these patients. Four hundred and sixty-four patients
      were asymptomatic and 36 patients presented with palpable breast or axillary
      masses. Specific mammographic features of a mass, microcalcifications,
      architectural distortion and asymmetric density were evaluated. Diagnosis was
      confirmed by fine needle aspiration biopsy or surgical excision in all patients.
      RESULTS: Four hundred and sixty-four patients had screening mammograms and 36
      patients had diagnostic mammograms. All 36 symptomatic patients had abnormal
      mammograms. Of these, 12 (33.33%) patients were found to have second primary
      breast carcinoma, 12 (33.33%) had metastases to the contralateral breast or
      axillary lymph nodes, six (16.66%) had fibroadenomas, two (5.55%) had abscesses,
      three (8.33%) had fibrocystic change, and one (2.77%) had axillary node reactive
      hyperplasia. Of the 464 asymptomatic patients, five (1.07%) had second primary
      breast carcinoma, five (1.07%) had fibrocystic change, and two (0.43%) had
      fibroadenomas. The mean age at the time of diagnosis of the first primary
      carcinoma in the symptomatic patients was 41.9 years (range 35-60 years), and was
      43.4 years (range 36-56 years) in the screening group. The mean time interval
      between the two carcinomas was four years (range one to 13 years) in symptomatic
      group and 3.4 years (range one to four years) in screening group. The tumour
      stage in the screened group was in situ (n = 2), stage I (n = 3) and in the
      symptomatic group was stage I (n = 2), stage II (n = 5), stage III (n = 5).
      CONCLUSION: Patients who have ipsilateral breast carcinoma have a strong risk to
      develop a second primary carcinoma in the contralateral breast. Close follow-up
      of the second breast with careful clinical examination and mammography are
      necessary for the early detection of cancer.

PMID- 12188075
TI  - Teaching first-year medical students physiology: does the human patient simulator
      allow for more effective teaching?
AB  - BACKGROUND: Although the Human Patient Simulator (HPS) is an effective teaching
      tool in many medical fields, literature supporting its use in the teaching of
      physiology to medical students is lacking. This study investigated the
      effectiveness of HPS-based teaching of cardiovascular physiology to first-year
      medical students. METHODS: Two hundred and ten first-year medical students were
      scheduled to our HPS laboratory with the purpose of demonstrating "physiology in
      action". Students were divided into groups of 19-25 each, and attended a lecture
      followed by a HPS session. Using a theatre-type simulator complete with
      mannequin, anaesthesia machine and monitors (METI, Sarasota FL), the scenarios of
      hypovolaemia, sepsis, and cardiac failure were run to demonstrate the
      physiological changes that occur with changes in preload, afterload, and cardiac
      contractility. Each student was given a true/false test before, and again after
      the HPS session, followed by a survey of their learning experience. RESULTS:
      There was marked improvement in test scores after the HPS session (82.1% vs.
      64.6%, P < 0.001). Most of the students felt that HPS was a better teaching tool
      (94.5%) and raised more questions (76.5%) than lectures. They wanted more topics
      to be taught this way (96%), as they could apply and re-enforce textbook
      knowledge, and visualise real-time changes. However, they felt that their
      experience could have been enhanced with more time and smaller groups.
      DISCUSSION: HPS is an excellent teaching tool as it stimulates student curiosity
      and makes knowledge acquisition and understanding easier. It is highly desirable
      to be incorporated into the teaching of physiology.

PMID- 12188074
TI  - Grip strength: effect of hand dominance.
AB  - AIM OF THE STUDY: Reliable and valid evaluation of hand strength is important for
      determining the effectivity of treatment strategies and it is accepted that grip
      and pinch strength provide an objective index for the functional integrity of
      upper extremity. This study was designed to evaluate the grip and pinch strength
      differences between sides for the right and left handed population. METHODS: The
      study included 128 right and 21 left hand dominant volunteers. Grip strength of
      the participants were measured by using a Jamar dynamometer. Pulp pinch strength
      measurements were performed by manual pinchmeter. RESULTS: When the study group
      was totally evaluated, a statistically significant difference was found between
      the grip and pinch strengths of dominant and nondominant hands in favour of the
      dominant hand. For further information we grouped 149 participants as right and
      left handed and investigated the number of subjects with stronger nondominant
      hand for each group. The percentage of stronger nondominant hand grip was 10.93%
      and 33.33% for right and left handed groups respectively. The results were less
      significant for pinch strength with 28.12% and 28.57% for right and left handed
      subjects respectively. CONCLUSION: We concluded that the dominant hand is
      significantly stronger in right handed subjects but no such significant
      difference between sides could be documented for left handed people.

PMID- 12188076
TI  - Gender differences in outcome after an acute myocardial infarction in Singapore.
AB  - OBJECTIVES: To characterise gender and age-related differences in presentation
      and outcome after an acute myocardial infarction (AMI). DESIGN: Data were derived
      retrospectively from the Singapore Myocardial Infarction Registry from 1988
      through 1997. This database comprised all AMI cases for ages between 20 and 64
      years (group A). For approximately three months a year, data were also collected
      for all AMI cases above the age of 64 years (group B). There were 13,048 and
      4,425 cases in groups A and B respectively. RESULTS: In age - standardised AMI
      rates, males outnumbered females by a factor of 4.0 and 1.7 for groups A and B
      respectively.The median age of presentation was higher in females for both age
      groups being 58 years versus 54 years for group A and 75 years versus 72 years
      for group B. Younger females had worse survival at 28 days and were more likely
      to have prior ischaemic heart disease and require resuscitation. They were also
      more likely to have atypical symptoms. Previous myocardial infarction was not
      different between the sexes in both groups. Among the older age group, there was
      no gender difference in prior ischaemic heart disease, 28-day survival and
      requirement for resuscitation. CONCLUSION: Women who have AMI tend to be older
      than men. Gender differences are age-specific. Women who are 64 years and below
      have more atypical symptoms, prior ischaemic heart disease and worse prognosis
      than men after AMI. These differences are not seen in those over the age of 64.

PMID- 12188077
TI  - Lymphangioma of the epididymis.
AB  - We report herein a 39-year-old man with a left scrotal swelling. The clinical and
      ultrasonographic appearances were suggestive of epididymal cyst. Histopathology
      of the excised lesion was shown to be lymphangioma of the epididymis. The
      differential diagnoses of a swelling in the scrotum of a young man include both
      benign and malignant conditions. Lymphangioma of the epididymis is, however, a
      rare and unusual cause.

PMID- 12188078
TI  - Tuberculous paraplegia in pregnancy treated by surgery.
AB  - Tuberculous paraplegia in pregnancy is reported to be rare. Paraplegia due to
      tuberculosis has a good prognosis if surgical decompression and stabilisation are
      done early together with chemotherapy. Vaginal delivery is not contraindicated in
      pregnancy complicated by paraplegia, but is associated with problems related to
      the initiation and progression of labour. Performing spinal nursing on an
      unstable spine with a rapidly enlarging gravid uterus in the third trimester of
      pregnancy poses a significant challenge. We report successful simultaneous
      Caesarean section and surgical treatment of a paraplegic spine due to
      tuberculosis.

PMID- 12188079
TI  - Patient safety: review of the contemporary American experience.

PMID- 12188080
TI  - Patient safety and medical errors--a Singapore perspective.

PMID- 12188082
TI  - Relationship between serum, saliva and urinary cortisol and its implication
      during recovery from training.
AB  - This study examined the relationship among resting cortisol levels measured in
      serum (SER), saliva (SAL). overnight urine (ON) and 24 h urinary free cortisol
      (24 h) samples to determine which would be most appropriate for monitoring
      recovery from the physiological stress imposed by exercise training. Eight (3
      female, 5 male) physical education students (X+/-SD age= 22+/-2 y, mass= 73.6+/
      17.1 kg; predicted 120m shuttle] VO2max = 3.83+/-1.34 L x min(-1); 51.4+/-8.0 mL
      x kg(-l) x min(-1)) volunteered. Venous blood, saliva and urine were collected
      following one day of recovery from training. Morning (0730-0800 h) cortisol was
      analysed commercially using solid phase radioimmunoassay. Mean resting cortisol
      concentrations for these samples were in the high end of the normal reference
      interval previously reported for this population in the literature: SER (656.5+/
      122.3 nmol x L(-1)). SAL (41.9+/-12.3 nmol x L(-1)), ON (72.0+/-19.5 nmol x L(
      1)) and 24 h (170.8 +/-58.7 nmol x day(-1)). Intraclass correlation coefficients
      (R) showed a high correlation between 24 h versus SER (R=0.99), SAL (R=0.97), and
      ON (R=0.97) cortisol, and between SER and SAL cortisol (r=0.99) Limits of
      agreement analysis to determine measurement error also revealed significant
      correlations (r2=0.60-0.99) between the dependent variables. In conclusion, the
      strong intraclass correlation coefficient between 24 h cortisol versus SAL and
      SER suggests that either sample can be used to monitor cortisol hormone during a
      recovery period from exercise training. The use of SAL samples for cortisol
      analysis may have many advantages due to its non-invasive nature.

PMID- 12188081
TI  - Clinics in diagnostic imaging (73). Left hydronephrosis due to pelvi-ureteric
      junction obstruction.
AB  - A full-term male infant was antenatally diagnosed to have left hydronephrosis.
      Post natal ultrasonography (US) and diuretic renography confirmed the diagnosis
      of left pelvi-ureteric junction obstruction. His clinical course was complicated
      by one episode of urinary tract infection. Serial US and diuretic renography
      showed no improvement in the obstruction. The patient underwent an Anderson-Hynes
      pyeloplasty at nine months of age with no post-operative complications. The
      diagnosis and management of antenatally-diagnosed hydronephrosis are discussed.

PMID- 12188083
TI  - Comparison of buoyancy, passive and net active drag forces between Fastskin and
      standard swimsuits.
AB  - A cross-sectional comparison between the buoyancy, passive and net active drag
      force characteristics of full-length, Fastskin swimsuits with that of standard
      swimsuits was completed with nine Open National level swimmers (5 males and 4
      females). Subjects were weighed in a hydrostatic tank and then towed via a
      mechanical winch on the surface and 0.4 m deep at 1.6, 2.2 and 2.8 m/s. The
      subjects performed a prone streamlined glide and maximum effort flutter kick at
      each towing velocity and depth. Hydrostatic weight differences between swimsuit
      types were not significant (p> 0.05. Fastskin passive drag values were
      significantly less than normal swimsuits during surface towing at 1.6 and 2.8
      m/s: and at 0.4 m deep towing at 1.6, 2.2 and 2.8 m/s. Net active drag force
      values also were lower for the Fastskin suits when compared with those of normal
      swimsuits and a significant difference existed for surface towing at all three
      velocities of 1.6, 2.2 and 2.8 m/s. The full-length, Fastskin swimsuits created
      less total hydrodynamic resistance than normal swimsuits while providing no
      additional buoyancy benefits.

PMID- 12188084
TI  - Sports medicine professionals cover a multiplicity of disciplines.

PMID- 12188085
TI  - Video analysis of selected game activities in Australian Rules Football.
AB  - The frequency and outcome of common game activities during Australian football
      matches have not previously been reported. The aim of this investigation was to
      determine the frequency and outcome of marking opportunities (MO), ruck contests
      (RC) and kick-ins (KI). for the purpose of potentially refining current training
      methods to better replicate common game occurrences. Video footage of all 24
      Australian Football League (AFL) matches in which the West Coast Eagles (WCE)
      participated during the 1997 premiership season was viewed. Notational analysis
      was used to record information for both the WCE and the opposition during MO, RC
      and KI. There was an average of 259 MO per game, of which 42.5% were unopposed by
      either team (1/0 or 0/1) and 45.0% involved one player from each team (1/1). The
      average success rate of unopposed marks (1/0 and 0/1) was 88.3%, opposed (1/1)
      29.3% and, for all MO's combined, 53.5%. There was an average of 99 RC per game,
      of which 48 were bounce-downs (28 centre bounces) and 51 boundary throw-ins. The
      clearance rates from RC for WCE and the opposition were not associated with
      winning the match or each quarter (p> 0.05, R = 0.000), nor did the clearance
      rate correlate with other measures of game success (scoring shots, team quarter
      score, the difference in score between teams or the lead change each quarter).
      There was an average of 21 KI per game. For both teams combined, long kicks (over
      50 metres) were the most preferred form of KI (49%) compared to medium (between
      25 and 50 metres) (30%) and short (under 25 metres) (21%). Long kicks were the
      most ineffective at directly retaining possession (29.0%) whilst short kicks were
      the most effective (93.4%). Some practical (training) implications, based on
      these results, are discussed.

PMID- 12188086
TI  - Grade III acromioclavicular joint injury in Australian Rules Football.
AB  - We have reviewed fourteen Australian Rules Football players who were seen
      consecutively by a single surgeon with grade III acromioclavicular joint injuries
      between January 1993-June 1997. After discussion at initial consultation eight
      players elected for non-operative management and six for operative management.
      Two players in the non-operative group subsequently underwent surgical
      reconstruction after failure of non-operative treatment. The mean return time to
      non-contact training was 2.4 weeks (range 1-4, S.D. 1.52) in the non-operative
      group and 6.3 weeks (range 3.5-10, S.D. 2.99) in the operative group. However
      return to sports specific training (contact training) was at a mean of 20.8 weeks
      (range 10-32. S.D. 8.56) in the non-operative group and 13.6 weeks (range 6-24.
      S.D. 7.06) in the operative group. Return to competitive football matches for the
      non-operative group was at a mean of 26.2 weeks (range 10-34,S.D. 8.84) and 18.8
      weeks (9.5-28. S.D. 8.05) for those treated operatively. These results were not
      statistically significant. At final follow up the subjective scores for the
      current overall condition of the shoulder when compared to the uninjured side,
      were 72.5 (range 20-100, S:D.24.9) for the non operative group and 87.3 (range 75
      100, S:D.10.61) for the operative group and this difference was also not
      statistically significant. Conclusions in this study are limited by small numbers
      and lack of statistically significant results. The results show a trend towards
      faster return to ARF and a more satisfactory outcome for patients undergoing
      surgery compared to their non operative cohorts.

PMID- 12188087
TI  - Australian football: injury profile at the community level.
AB  - Successful injury prevention relies on injury surveillance to establish the
      extent of the problem, to monitor injury patterns and to evaluate prevention
      strategies. Despite the popularity of participation in Australian football at the
      community level, few injury surveillance studies have been published describing
      the pattern of injuries at this level of participation. In contrast, ongoing
      injury surveillance at the elite-level is well established. Reliance on injury
      data from the elite-level of Australian football to guide injury prevention at
      the community level may not be appropriate due to differences across the levels
      with respect to exposure, fitness and skill level. Therefore, specific injury
      surveillance at the community level of Australian football is warranted. This
      study describes the epidemiology of community level Australian football injuries.
      Injury surveillance was undertaken in five amateur Australian football clubs over
      the 1999 season. The 320 participating players sustained 421 injuries over the
      season. The overall rate of injury was 27 injuries per 1000 player hours.
      Injuries were most commonly sustained at the start of the season and during the
      second quarter of match participation. Hamstring muscle strains were the most
      common injury sustained, followed by thigh haematomas and lateral ligament
      sprains of the ankle. The injury surveillance system used in this study was well
      accepted by the clubs and provides detailed data for the prioritisation of future
      injury prevention research at the community level of Australian football.

PMID- 12188088
TI  - Bovine colostrum supplementation during endurance running training improves
      recovery, but not performance.
AB  - This study examined the effect of supplementation with concentrated bovine
      colostrum protein powder (intact) on plasma insulin-like growth factor I (IGF-I)
      concentrations, endurance running performance and recovery. Thirty physically
      active males completed 8 weeks of running training whilst consuming 60 g x day(
      1) of intact powder (n=17) or a concentrated whey protein powder placebo (n=13)
      in a randomised, double-blind, parallel design. Plasma IGF-I concentrations were
      measured prior to subjects performing two (approximately 30 min) incremental
      treadmill running tests to exhaustion (RUN1 and RUN2) separated by 20 min of
      passive recovery at Weeks 0. 4 and 8. Plasma IGF-I concentrations showed little
      change in either group (p=0.83). Effective peak running speed (PRSE; i.e.
      equivalent of peak power) during RUN1 was not different between groups at Week 0
      (p>0.99), and had increased by a similar amount in both groups by Week 4 (mean+/
      SD, intact 2.2+/-4.0%, placebo 3.2+/-3.3%; 95% confidence interval [95% CI 15.7
      to -13.7%; p=0.89) and Week 8 (intact 3.6+/-5.6%, placebo 3.4+/-4.4 %; 95% CI 
      100.0 to 100.0%; p>0.99). PRSE was less in both groups during RUN2 (p<0.05), but
      was not significantly different between groups at Week 0 (p>0.99). PRSE during
      RUN2 tended to have increased more in the placebo group by Week 4 (intact 1.8+/
      4.8%, placebo 4.2+/-3.9%; 95% CI 0.2 to -5 0%; p=0.07), but the intact group had
      increased PRSE significantly more by Week 8 (intact 4.6+/-6.1%, placebo 2.0+/
      4.5%; 95% Cl 0.0 to 5.2%; p=0.05). resulting in a significantly faster PRSE
      (p=0.003). We conclude that supplementation with intact powder did not increase
      plasma IGF-I concentrations or improve performance during an initial bout of
      incremental running to exhaustion in our sample. However, performance during a
      second bout of exercise may be improved by as much as 5.2% in the average subject
      after 8 weeks of supplementation, possibly due to an enhancement of recovery.

PMID- 12188089
TI  - Elite athletes: effects of the pressure to be thin.
AB  - This study represented the first attempt to examine the prevalence of eating
      disorders in a large sample of both male and female elite athletes compared to a
      matched control group of non-athletes. The subjects were 263 Australian elite
      athletes representing a variety of sports, and 263 non-athletes. All subjects
      were interviewed using the Composite International Diagnostic Interview and
      completed a number of self-report questionnaires. Both male and female athletes
      competing in sports that emphasise a lean body shape or a low body weight
      evidenced a significantly higher prevalence of eating disorders and eating
      disorder symptoms than other athletes and non-athletes. The results suggest that
      athletes do, in fact, have a higher prevalence of eating disorders than non
      athletes. However, it is not so much being an athlete that places an individual
      at increased risk for developing an eating disorder; rather it is athletes
      competing in sports which emphasise the importance of a thin body shape or a low
      body weight who appear to be particularly vulnerable.

PMID- 12188090
TI  - A reproducible and variable intensity cycling performance protocol for warm
      conditions.
AB  - This study was undertaken to assess the reproducibility of a variable
      intensitycycling protocol using subjects of varying abilities, under warm humid
      conditions. Eleven subjects (Age 21.4+/-2.6 years; VO2peak 3.30+/-0.9 l x min(
      1); peak power 322.8+/-86.3 W; mean+/-SD) performed a 60 min cycling trial
      punctuated with six one-min "all-out" sprints at 10-min intervals on three
      occasions 5-14 days apart. Ambient temperature and relative humidity were set at
      33+/-0.7 degrees C and 63+/-2.0%, respectively. Subjects used their own bicycle
      mounted to an electromagnetic trainer and were only permitted to monitor elapsed
      time and heart rate. Repeatability was assessed using the limits of agreement
      which were best between trials 2 and 3 where the distance cycled was -0.54 km
      below and 1.34 km above the distance cycled for trial 2. The co-efficient of
      variation (CV) for distance for three trials was 3.58%. For trials 1 and 2 the CV
      was 3.54% (r = 0.97, p< 0.001) decreasing to 1.34% (r = 0.99, p< 0.001) for
      trials 2 and 3. The intra-class correlation for three trials was 0.93. Distance
      for trial 1 (26.3+/-5.0 km; p< 0.05) was less than trials 2 (27.7+/-5.7 km) and 3
      (28.1+/-5.6 km). It was concluded that repeatability for this performance
      protocol with cyclists of varying abilities In warm humid conditions was
      acceptable given at least one familiarisation trial. However, it is not yet known
      whether other protocols designed for moderate environments are applicable to less
      favorable conditions. Further studies are needed before results of treatment
      effects under differing ambient conditions can be fully understood and assigned
      appropriate significance.

PMID- 12188091
TI  - Understanding some of the risks for soft tissue inury--a Malcolm Blight legacy?

PMID- 12188092
TI  - A qualitative and quantitative analysis of rhythmic activities during a mental
      task and sleep spindles.
AB  - The frequency, configuration, and distribution of sleep spindles are similar to
      some of the rhythmic activities seen during task performance. In the present
      study, the relationship between rhythmic activities during sleep and arithmetic
      addition was investigated in male university students with (n = 10) and without
      (n = 10) frontal midline theta activity (Fmtheta). Electroencephalograms (EEGs)
      during addition in both groups were compared at frontal and central areas on
      three consecutive days. Polysomnograms were recorded at the same regions on four
      consecutive nights for each group. The amount of theta rhythm during a mental
      task (Fmtheta) and in nocturnal sleep at Fz and Cz electrodes was greater for the
      Fmtheta group than for the non-Fmtheta group, while the amount of beta rhythm at
      both sites was smaller in the Fmtheta group than in the non-Fmtheta group. There
      were no differences between the groups in the amount of alpha rhythm at either
      site. The frequency of alpha rhythm at Fz and Cz in both situations was slower
      for the Fmtheta group than for the non-Fmtheta group, but there were no
      differences in the frequency of theta and beta rhythms between the groups at
      either site. These results suggest that rhythmic activities during a mental task
      and in sleep may correlate with each other.

PMID- 12188093
TI  - The relationship between rhythmic activities during a mental task and sleep
      spindles: a correlative analysis.
AB  - In a previous study, we suggested that the characteristics of theta, alpha, and
      beta rhythms during a mental task were similar to those during sleep. Building
      upon the previous data, correlations between rhythmic activities during a mental
      task and during sleep were investigated in the present study. Patterns of
      correlation and no correlation between rhythmic activities during the mental task
      were similar to those during sleep for subjects with and without frontal midline
      theta (Fmtheta) activity. In the Fmtheta group, there were no correlations
      between rhythmic activities in the two situations, while in the non-Fmtheta
      subjects, theta and alpha rhythms showed a positive correlation with one another,
      and theta and beta rhythms correlated negatively during sleep. In both groups,
      there were many correlations between rhythmic activities during the mental task
      and those in Sleep Stage 2, while there were few correlations between rhythmic
      activities during the mental task and those in other sleep stages. These results
      suggest that the mechanism generating rhythmic activities during the appearance
      of rhythmic activities induced by a mental task may be closely related to those
      of rhythmic activities during sleep, and that the membrane potentials in
      reticular thalamic (RE) neurons during the appearance of rhythmic activities
      induced by a mental task may be nearly equivalent to that in Sleep Stage 2, and
      that the correlation pattern between the rhythmic activities in each group may be
      well explained by the appearance pattern of each rhythm in the previous report.

PMID- 12188095
TI  - Functional magnetic resonance imaging study of word recognition in normal elders.
AB  - Four healthy, cognitively intact elders participated. Subjects underwent fMRI
      scanning while performing a word recognition task with an easy condition (low
      demand) and a difficult condition titrated to each subject's ability (titrated
      demand). Relative to low, titrated demand was associated with increased
      activation of the left medial frontal (cluster level P <.002), right superior
      temporal (P <.007) and right superior parietal cortices (P<.001). Increased
      activation of bilateral cortical areas by elders during the more challenging
      titrated demand compared with low demand may indicate recruitment of additional
      brain regions, enabling subjects to maintain performance despite increasing
      difficulty. Alternatively, the bilateral activation on this word recognition task
      may reflect compensatory use of right hemisphere networks.

PMID- 12188094
TI  - Dopamine receptors and learned helplessness in the rat: an autoradiographic
      study.
AB  - (1) Disturbances of mesolimbic and mesocortical dopamine (DA) function have been
      implicated in the pathophysiology of several psychiatric disorders, including
      major depressive disorder. (2) Utilizing the learned helplessness (LH) animal
      model of clinical depression and quantitative autoradiography, the authors
      studied the densities of D1 and dopamine-2-like receptors (D2-like receptors) in
      medial prefrontal cortex, septum, nucleus accumbens and caudate nucleus in rats
      that received inescapable stress and were subsequently tested for LH behavior.
      (3) Dopamine-1 receptor (D1 receptor) densities were significantly higher in the
      core and shell of the nucleus accumbens and in the medial caudate nucleus of rats
      that did not become helpless after stress, compared to rats that developed LH.
      (4) Densities of D2-like receptors were significantly lower in the core of the
      nucleus accumbens in both the LH and the nonhelpless (NH) rats compared to
      controls. Densities of D2-like receptors were also lower in the medial and
      lateral caudate nuclei in LH rats compared to the other groups. (5) Increased D1
      receptor densities in NH rats in the nucleus accumbens may be associated with an
      adaptive or protective role of this brain region in the prevention of escape
      deficits after exposure to inescapable stress. (6) Decreased D2-like receptor
      densities in the caudate nucleus in helpless rats may reflect a motor deficit
      associated with LH behavior, while decreases of D2-like receptor densities in the
      core of the nucleus accumbens may reflect a generalized effect of exposure to
      inescapable stress. (7) This study highlights the importance of the
      mesolimbic/nigrostriatal dopaminergic systems in mediating behavioral responses
      to inescapable stress.

PMID- 12188096
TI  - The effects of benzodiazepines on event-related potential indices of automatic
      and controlled processing in schizophrenia: a preliminary report.
AB  - The effects of benzodiazepines on cognitive function in schizophrenic patients
      were investigated using event-related potential (ERP) measurement during an
      auditory selective attention task. In this study, the authors compared the
      mismatch negativity (MMN) and N2b components between two subgroups of
      schizophrenic patients: one is comprised of patients who received no
      benzodiazepines (NT group, n = 7) and the other is comprised of those
      administered benzodiazepines in the daytime (T group, n = 7). There were no
      significant differences in MMN and N2b amplitudes between the two subgroups,
      whereas the N2b latency was significantly prolonged in the T group relative to
      the NT group. This suggested that benzodiazepines induce delayed stimulus
      classification processing in schizophrenic patients.

PMID- 12188097
TI  - Alcohol urge and plasma beta-endorphin change after alcohol challenge with
      naltrexone pretreatment in social drinkers.
AB  - The authors have investigated the effect of naltrexone (NTX) on lowering the urge
      of alcohol drinking and the action mechanism of NTX. Fifteen healthy male social
      drinkers voluntarily participated. The experimental method was a double-blind,
      placebo-controlled cross-over design. To eliminate NTX effect, 1 week washout
      cross-over interval was taken. Subjects ingested NTX, 50 mg/day, or placebo for 1
      week. Then, the alcohol (0.5 ml/kg) challenge test was done in the evening. Blood
      samples were taken immediately before drinking, at 20 min and at 60 min after
      alcohol drinking. Plasma beta-endorphin, plasma ACTH and serum cortisol levels
      were checked. Subjects completed self-report questionnaires such as the visual
      analog scales of drink urge and the alcohol sensation scales at regular
      intervals. In the case of NTX pretreatment, the subjects reported significantly
      (P=.013) less urge to drink alcohol on the self-reporting urge scales, especially
      at postdrinking 20 min and 60 min than placebo pretreatment. After alcohol
      challenge, the subjects reported significantly more dizziness (P=.015) in the
      case of NTX pretreatment, and reported less mood elevation trend, though not
      significant (P=.052). Basal plasma beta-endorphin levels were not different, but
      in the case of NTX pretreatment, the increasing degree of plasma beta-endorphin
      during 20 min after alcohol challenge was significantly (P=.039) higher than with
      placebo pretreatment. This results show that the NTX reduced the urge to drink
      alcohol with the mechanism of partially blocking the opioid positive reward
      system and partially mimicking the alcohol effect.

PMID- 12188098
TI  - Nefazodone treatment of dysthymic disorder an open, long-term, prospective pilot
      study.
AB  - Dysthymic disorder, described by the Diagnostic and Statistical Manual of Mental
      Disorders--4th edition (DSM-IV) criteria as a chronically depressed mood that
      occurs most of the day more days than not for at least 2 years and has a lifetime
      prevalence rate of approximately 3.3% [Gwirtsman, 1994. Psychopharmacol. Bull. 30
      (1994) 45.]. This disorder, which is disabling, often goes unrecognized and its
      sufferers are often undertreated, but recent evidence has suggested that people
      with dysthymia may respond to antidepressant treatment. Based on effective
      outcomes in previous studies using fluoxetine (a 5-HT reuptake inhibitor) and
      ritanserin (a 5-HT2A antagonist), it was hypothesized that nefazodone, which is
      both a serotonin (5-HT) reuptake inhibitor (rather weak) and a 5-HT2A receptor
      antagonist, may provide an effective treatment for patients with dysthymic
      disorder. Six participants completed this 24-week pilot trial. A decrease in the
      Hamilton Rating Scale for Depression (HAM-D) scores was observed from baseline to
      Week 24, although most changes occurred in the first 4 weeks of participation.
      There was an improvement in anxiety symptomatology, both physiological and
      psychological. General functioning did not improve as observed by Global
      Assessment of Functioning Scale (GAF) scores. There may be some benefit to
      nefazodone for treatment of dysthymia, as indicated by positive results on HAM-D,
      Hamilton Anxiety Scale (HAM-AD), and Hopkins Symptom Checklist (HCL) scores
      within the first 4 weeks; however, it is possible that such dramatic results may
      be due to entry into the study alone, and not to medication.

PMID- 12188099
TI  - Sulphatoxymelatonin excretion during opiate withdrawal: a preliminary study.
AB  - The excretion of sulphatoxymelatonin (aMT6S), a major metabolite of melatonin in
      urine, is dependent on noradrenergic (NA) neuronal activity within the pineal
      gland and thus represents a neuroendocrine marker of NA neuronal function. Many
      of the clinical features of opiate withdrawal result from increased firing of
      central NA neurones. In this study, we test the hypothesis that aMT6S excretion
      is increased during opiate withdrawal in opiate-dependent patients. The 24-h
      urinary aMT6S excretion was measured at three time points during in-patient
      methadone detoxification treatment in 11 opiate-dependent patients, during
      methadone stabilisation and on Days 6 and 12 of withdrawal treatment. There was a
      significant increase in aMT6S excretion on Day 6 but not on Day 12, compared to
      stabilisation. A significant correlation between individual withdrawal symptom
      score severity and aMT6S excretion was demonstrated during stabilisation (r=.68,
      P<.05) and on Day 6 of treatment (r=.62, P<.05). Our preliminary findings suggest
      that melatonin secretion may represent a neuroendocrine marker of NA neuronal
      hyperactivity during opiate withdrawal in opiate-dependent patients. Areas of
      future research are discussed.

PMID- 12188100
TI  - Biological markers and possibilities for predicting therapeutic results in
      schizophrenia: a methodological contribution.
AB  - The aim of the research was to select some easily available and easily replicable
      biological markers that could be used as predictors of both acute and long-term
      therapy. A selection of state markers (structural computer tomography [CT]
      parameters, psychological parameters, tests concentrating on attention and
      memory, "soft signs"), trait markers (quantified electroencephalograph [QEEG],
      cortisolemia, prolactinemia [PRL], and their changes) and clinical symptoms
      (Positive and Negative Syndrome Scale [PANSS], Clinical Global Impression [CGI])
      were determined in 52 hospitalised schizophrenic patients showing either an acute
      episode or an exacerbation. The evaluation was repeated after one year of
      outpatient therapy. The parameters studied so far are not sufficiently specific
      and sensitive; therefore, the prediction cannot be based on a single parameter.
      In order to overcome this shortcoming, we carried out the analysis by means of
      multidimensional statistics, applying discriminant analysis. The results of both
      a broader and a more specific approach are stated in the paper. In all the used
      examples of discriminant analysis, the optimum discriminator is cortisolemia or
      its changes after administering dexamethasone and structural CT parameters. The
      results indicate that combinations of vulnerability markers and state markers
      (cortisolemia) may be of predictive value and are compatible with the
      vulnerability-stress ethiopathogenetic model of schizophrenia.

PMID- 12188101
TI  - Detection of TOAD-64 in adult rat brain as revealed by two-dimensional protein
      gel electrophoresis followed by MALDI mass spectrometry possible modulatory
      effect of chronic haloperidol treatment.
AB  - The molecular mechanisms by which antipsychotic effects are achieved remain
      largely elusive. Possible mechanisms include the modulation of nerve cell gene
      expression. The antipsychotic drug haloperidol was administered orally (1.6
      mg/kg) to adult rats for 3 weeks. Protein patterns in striata and forebrains were
      studied by two-dimensional gel electrophoresis (2-DE). One differentially
      regulated protein spot was identified by matrix-assisted laser desorption
      ionization mass spectrometry (MALDI-MS) after trypsin digest. Turned on after
      devision-64 kD (TOAD-64), the identified protein, was present in all gels and, in
      addition, was up-regulated in the striata but not in the forebrains of the
      haloperidol-treated animals by 43%. It is concluded that TOAD-64, typically
      regarded as a marker for commitment to neuronal differentiation during fetal
      development, also plays a role in adult rat forebrain and striatum and that its
      concentration is possibly modulated by haloperidol treatment.

PMID- 12188102
TI  - Evidence from a population pharmacokinetics analysis for a major effect of CYP1A2
      activity on inter- and intraindividual variations of clozapine clearance.
AB  - Interindividual variations of clozapine clearance could be related to individual
      CYP1A2 activity. A population approach was used to investigate clozapine
      pharmacokinetics of multiple doses of clozapine in patients. Clozapine plasma
      concentrations were obtained in 23 patients from therapeutic drug monitoring (83
      samples). CYP1A2 activity was estimated by the norclozapine/clozapine plasma
      levels ratio and data were processed by a nonlinear mixed-effect modelling
      method. Different covariates (age, body weight, height, CYP1A2 activity, daily
      dose of clozapine) were tested but CYP1A2 activity was the single parameter that
      improved significantly the predictive model. The best fit was obtained by
      integration of a linear relationship between clozapine clearance and CYP1A2
      activity. The findings suggest that (i) CYP1A2 activity is a major factor that
      determines clozapine clearance and (ii) the norclozapine/clozapine ratio could
      constitute a valuable measure of the CYP1A2 activity. This ratio can be simply
      determined in the context of therapeutic drug monitoring and could explain the
      inter- and intraindividual variation of clozapine plasma levels.

PMID- 12188104
TI  - Impact of Alzheimer's disease and rivastigmine treatment on activities of daily
      living over the course of mild to moderately severe disease.
AB  - OBJECTIVES: To investigate the relationship between activities of daily living
      (ADL) impairment and Alzheimer's disease (AD) severity in mild to moderately
      severe AD patients receiving the cholinesterase (ChE) inhibitor rivastigmine.
      METHODS: ADLs were evaluated using the Progressive Deterioration Scale (PDS).
      Disease severity was assessed with the Global Deterioration Scale (GDS). Patients
      were participants in one of three double-blind, placebo-controlled trials with
      rivastigmine. RESULTS: Baseline PDS scores differed significantly (P<.001) by
      disease severity. At Week 26, PDS declines from baseline for placebo patients
      were significantly different at all disease stages. Specific ADL affected were
      disease stage-dependent. Rivastigmine treatment (6-12 mg/day) resulted in total
      PDS scores being significantly improved compared with placebo at all disease
      stages, although the effect on individual items differed by severity.
      CONCLUSIONS: ADL impairment differs across the stages of AD. Greater impairment
      in total ADL scores is observed with increasing severity of illness. However, the
      stage of illness determines the type of ADLs lost. Treatment response to
      rivastigmine occurs with mild, moderate and moderately severe AD, with the
      largest effect in patients with advancing severity of disease.

PMID- 12188103
TI  - Long-term effects of rivastigmine in moderately severe Alzheimer's disease: does
      early initiation of therapy offer sustained benefits?
AB  - Goals of the study included evaluating the long-term efficacy of rivastigmine in
      Alzheimer's disease (AD) patient categories stratified by baseline dementia
      severity, and post hoc investigation of particular benefits of early initiation
      of rivastigmine treatment in moderately severe AD. Both rivastigmine-treated
      groups (originally randomized to 1-4 or 6-12 mg/day) experienced significantly
      smaller declines in Alzheimer's Disease Assessment Scale-Cognitive subscale (ADAS
      Cog) scores from baseline than the projected placebo group after 52 weeks.
      Patients receiving rivastigmine from Day 1 experienced significantly less decline
      compared with patients originally receiving placebo and then initiating
      rivastigmine treatment after a 6-month delay. Furthermore, cognitive benefits
      were more robust in patients with moderately severe disease compared with
      previous reports in mild to moderately severe AD. Findings suggest that early
      treatment with rivastigmine 6-12 mg/day is associated with sustained long-term
      cognitive benefits in patients with moderately severe AD. The results support the
      value of early treatment of AD patients, particularly those with moderately
      severe AD.

PMID- 12188105
TI  - A molecular basis of the therapeutic and psychoactive properties of cannabis
      (delta9-tetrahydrocannabinol).
AB  - All of the therapeutic properties of marihuana (analgesic, antiemetic, appetite
      stimulant, antiglaucoma) have been duplicated by the tetrahydrocannabinol (THC)
      molecule or its synthetic derivatives. Today, the molecular mechanisms of action
      of these compounds have led to a general understanding of the pharmacological
      effects of marihuana and of its therapeutic properties. These mechanisms involve
      the specific binding of THC to the 7-transmembrane (7TM) domain G protein-linked
      receptor, a molecular switch which regulates signal transduction in the cell
      membrane. The natural ligand of the 7TM receptor is an eicosanoid,
      arachidonylethanolamide (AEA), generated in the membrane and derived from
      arachidonic acid. THC acts as a substitute ligand to the 7TM receptor site of
      AEA. THC would deregulate the physiological function of the 7TM receptor and of
      its ligand AEA. As a result, the therapeutic effects of the drug may not be
      separated from its adverse psychoactive and cardiovascular effects. The binding
      of THC to the 7TM receptor site of AEA induces allosteric changes in the receptor
      sites of neurotransmitter and opiates resulting in variable interactions and
      pharmacological responses. The pharmacokinetics of THC with its prolonged storage
      in fat and its slow release result in variable and delayed pharmacological
      response, which precludes precise dosing to achieve timely therapeutic effects.
      The experimental use of THC and of its synthetic analogues, agonists, and
      antagonists has provided novel information in the nature of molecular signaling
      in the cell membrane. As a result, the relationships between allosteric receptor
      responsiveness, molecular configuration of proteins, and physiological regulation
      of cellular and organ function may be further investigated.

PMID- 12188106
TI  - Interferon alpha (IFNalpha) and psychiatric syndromes: a review.
AB  - Interferon alpha (IFNalpha) is used for the treatment of several disorders, such
      as chronic hepatitis or malignant melanoma. During the therapy, IFNalpha may
      cause severe neuropsychiatric syndromes including depression with suicidal
      ideation, paranoid psychoses, or confusional states. The reasons and management
      of these side effects are widely unknown. Our aim is to review research evidence
      for the contribution of IFNalpha for the etiopathology of psychiatric syndromes.
      Therefore, research findings of neuropsychiatric syndromes induced by IFNalpha
      treatment, the putative mechanisms underlying those syndromes, and their
      treatment are-reviewed. Furthermore, neuropsychiatric syndromes in diseases with
      high IFNalpha levels such as systemic lupus erythematosus (SLE) are discussed.
      Finally, the question is addressed whether IFNalpha may contribute to the
      etiopathology of endogenous psychiatric disorders. IFNalpha may cause psychiatric
      syndromes in a subset of treated patients. The underlying pathogenetic mechanisms
      include various effects on neuroendocrine, cytokine, and neurotransmitter
      systems. Research data on the role of IFNalpha in the pathogenesis of endogenous
      psychiatric disorders are conflicting. Future research should improve our
      understanding of the role of IFNalpha for the etiopathology of psychiatric
      syndromes and has an impact on treatment of IFNalpha-induced psychiatric
      syndromes.

PMID- 12188107
TI  - Animal models of anti-HIV drugs exposure during pregnancy: effects on
      neurobehavioral development.
AB  - In the last 10 years, zidovudine (AZT) has become the main prophylactic therapy
      against vertical HIV-1 transmission. AIDS Clinical Trials Group (ACTG) 076 have
      demonstrated that the administration of AZT to HIV-infected women during their
      third trimester of pregnancy, trough labor and given orally to babies for 6
      weeks, reduced by two-thirds the rate of vertical infection. Although the rapid
      diffusion of this regimen into clinical practice together with the implementation
      of HIV counseling and testing practices have dramatically reduced the vertical
      transmission rate in the US and Western Europe, there is a growing concern on the
      adverse effects of antiretroviral therapy on the fetus and the newborn. In fact,
      even though shorter regimen therapies that are less complex and expensive to
      implement in poor countries have been demonstrated as effective as ACTG 076
      regimen, the distribution of the risk of vertical transmission in the developing
      countries is still very high. Consequently, a large number of unborns will be a
      candidate to developmental exposure to antiretroviral agents. To date, data on
      the transplacental mutagenicity, carcinogenicity and mitochondrial dysfunction
      induced by developmental exposure to AZT have been reported in several animal
      models. Furthermore, one study reported severe yet few human cases of
      cardiomyopathy and neurological disease likely associated with mitochondrial
      dysfunction in uninfected infants of seropositive mothers perinatally exposed to
      AZT. For all of these reasons, many investigations have been focusing on the
      assessment of the potential adverse effects of nucleoside reverse transcriptase
      (RT) inhibitors (NRTI) administration during development. A survey of the main
      results derived from clinical and animal studies is reported here, focusing on
      those neurobehavioral studies that have been looking for specific and/or
      aspecific changes in the nervous system induced by NRTI exposure in utero.

PMID- 12188108
TI  - Residual symptoms in depression an emerging therapeutic concept.
AB  - Cushing's syndrome is due to chronic glucocorticoid excess that may have various
      etiologies. The most common endogenous form is pituitary-dependent bilateral
      adrenal hyperplasia, which is termed Cushing's disease. Major depression occurs
      in more than half of the cases. The presence of depressive symptoms connotes
      severity of clinical presentation and, in patients with hypothalamic-pituitary
      forms, entails prognostic value. Medical treatment may be used while awaiting
      more definitive solutions for the illness by surgery. The inhibitors of steroid
      production (e.g., ketoconazole, metyrapone and aminoglutethimide), rather than
      antidepressant drugs, are generally successful in lifting depression as well as
      other disabling symptoms. Since central serotonergic regulation could have a role
      in the course of Cushing's disease, serotonin antagonists (e.g., cyproheptadine,
      ritanserin and ketanserin) have been employed. Findings related to the
      pharmacological response of depression in Cushing's disease were found to have
      implications for the pathophysiology of depression and the potential involvement
      of the hypothalamic-pituitary-adrenal axis (HPA axis) in resistance and tolerance
      to antidepressant drugs. The use of serotonergic drugs in Cushing's disease may
      yield important insights in the understanding of serotonergic regulation both in
      Cushing's disease and in the HPA axis in nonendocrine major depression.

PMID- 12188110
TI  - Abnormal P300 in a case of delusional misidentification with coinciding Capgras
      and Fregoli symptoms.
AB  - The Delusional Misidentification Syndrome (DMS) is thought to be related to
      dissociation between recognition and identification processes. Working memory
      (WM) is considered responsible for the integration and online manipulation of
      information, so that it is available for further processing. Since the P300
      component of event-related potentials (ERPs) is considered as an index of the on
      line updating of WM, the present study is focused on auditory P300 elicited
      during a WM test in DMS, compared with that in healthy controls. ERPs, elicited
      during a WM test, in a case suffering from coinciding Capgras and Fregoli
      symptoms, were recorded. Peak amplitude and latency of the averaged P300
      waveforms, as well as memory performance of this case, were compared to the
      patterns obtained from healthy controls. In relation to normal controls, the
      patient exhibited significantly attenuated amplitude of P300 at the F4, P3 and Pz
      abductions. The patient also showed significantly prolonged latencies of P300 at
      all abductions used. These findings suggest that DMS may be accompanied by WM
      dysfunction affecting brain regions outside the prefrontal cortex, as well as
      within, and by diffuse failure to allocate attention resources to a stimulus, as
      they are reflected by P300 amplitudes and latencies respectively. Additionally,
      it may be suggested that techniques designed to explore cognitive operations,
      such as recording of ERPs, and more specifically P300, during WM tasks, could
      provide further insights into the relationship between neural functioning and the
      cognitive deficits in DMS.

PMID- 12188109
TI  - Physiology and pathophysiology of cortico-basal ganglia-thalamocortical loops:
      theoretical and practical aspects.
AB  - A new theoretical framework is used to analyze functions and pathophysiological
      processes of cortico-basal ganglia-thalamocortical loops and to demonstrate the
      hierarchical relationships between various loops. All hierarchical levels are
      built according to the same functional principle: Each loop is a neural optimal
      control system (NOCS) and includes a model of object behavior and an error
      distribution system. The latter includes dopaminergic neurons and is necessary to
      tune the model to a controlled object (CO). The regularities of
      pathophysiological processes in NOCSs are analyzed. Mechanisms of current
      functional neurosurgical procedures like lesioning and deep brain stimulation
      (DBS) of various basal ganglia structures and neurotransplantation are described
      based on proposed theoretical ideas. Parkinson's disease (PD) is used to
      exemplify clinical applications of the proposed theory. Within the proposed
      theoretical framework, PD must be considered as a disease of the error
      distribution system. The proposed theoretical views have broad fundamental and
      clinical applications.

PMID- 12188111
TI  - Drug maintenance treatment compliance and its correlation with the clinical
      picture and course of schizophrenia.
AB  - The relationship between patients compliance with their drug therapy regime and
      important predictors of schizophrenia was studied on the basis of a 7-year
      observation (from the onset of illness) of 185 schizophrenic patients. Compliant
      patients (N= 57) were compared with noncompliant patients (N=37). The two groups
      were matched for age at onset, sex, social background and presence of
      precipitating factors. The compliant patients had better occupational and family
      adjustment, less intense behaviour disorders prior to the onset of schizophrenia,
      a shorter term of untreated first psychosis. These patients also had shorter
      periods of untreated relapses and longer remissions. They had more often insight
      of their disease whereas serious signs of defect were less frequent. They had
      later onset of disturbances of self-activity, vitality and identity. The results
      of this study suggest that with compliance with a neuroleptics drug treatment
      regime does not affect the number of admissions in the hospital but is related to
      longer remissions and less intense signs of deficiency.

PMID- 12188112
TI  - Improvement of tardive dyskinesia following switch from neuroleptics to
      olanzapine.
AB  - The authors report two cases of schizophrenia in which olanzapine proved to be an
      efficacious antipsychotic medication associated with the remission of movement
      disorder.

PMID- 12188113
TI  - Semi-continuous anaerobic digestion of solid poultry slaughterhouse waste: effect
      of hydraulic retention time and loading.
AB  - We studied the effect of hydraulic retention time (HRT) and loading on anaerobic
      digestion of poultry slaughterhouse wastes, using semi-continuously fed,
      laboratory-scale digesters at 31 degrees C. The effect on process performance was
      highly significant: Anaerobic digestion appeared feasible with a loading of up to
      0.8 kg volatile solids (VS)/m3 d and an HRT of 50-100 days. The specific methane
      yield was high, from 0.52 to 0.55 m3/kg VS(added). On the other hand, at a higher
      loading, in the range from 1.0 to 2.1 kg VS/m3 d, and a shorter HRT, in the range
      from 25 to 13 days, the process appeared inhibited and/or overloaded, as
      indicated by the accumulation of volatile fatty acids and long-chain fatty acids
      and the decline in the methane yield. However, the inhibition was reversible. The
      nitrogen in the feed, ca. 7.8% of total solids (TS), was organic nitrogen with
      little ammonia present, whereas in the digested material ammonia accounted for 52
      67% (up to 3.8 g/l) of total nitrogen. The TS and VS removals amounted to 76% and
      64%, respectively. Our results show that on a continuous basis under the studied
      conditions and with a loading of up to 0.8 kg VS/m3 d metric ton (wet weight) of
      the studied waste mixture could yield up to 140 m3 of methane.

PMID- 12188114
TI  - Environmental context of Cylindrospermopsis raciborskii (Cyanobacteria) blooms in
      a shallow pond in France.
AB  - Cylindrospermopsis raciborskii, a potentially toxic blooming cyanobacterium (blue
      green alga), responsible for public health problems in Australia, was identified
      in France in 1994 in a shallow pond south of Paris. A program monitoring the
      occurrence of C. raciborskii in this pond was conducted from July 1998 to October
      1999. The phytoplankton assemblages were studied, and limnological parameters
      (water temperature, dissolved oxygen, pH, conductivity, and dissolved inorganic
      nutrients) were measured. By multivariate analysis (principal component
      analysis), we showed that sufficiently high temperatures to allow the germination
      of akinetes, relatively low nutrient concentrations (soluble reactive phosphorus
      with a mean concentration of 1 microM and nitrate between 0 and 5 microM, except
      in February 1999 (21 microM)) and a characteristic high and constant sulfate
      concentration (8981+/-471 microM) seemed to be the main factors involved in the
      proliferation of C. raciborskii in the "Francs-Pecheurs" (FP) pond. In the light
      of these findings and of bibliographic data, C. raciborskii would seem to be
      characterized by good adaptability, but also by low competitiveness with other
      phytoplanktonic species in the temperate study area.

PMID- 12188115
TI  - Biological leaching of Mn, Al, Zn, Cu and Ti in an anaerobic sewage sludge
      effectuated by Thiobacillus ferrooxidans and its effect on metal partitioning.
AB  - The chemical fractionation and bioleaching of Mn, Al, Zn, Cu and Ti in municipal
      sewage sludge were investigated using Thiobacillus ferrooxidans as leaching
      microorganism. As a result of the bacterial activity, ORP increase and pH
      reduction were observed. Metal solubilization was accomplished only in
      experimental systems supplemented with energy source (Fe(II)). The solubilization
      efficiency approached approximately 80% for Mn and Zn, 24% for Cu, 10% for Al and
      0.2% for Ti. The chemical fractionation of Mn, Al, Zn, Cu and Ti was investigated
      using a five-step sequential extraction procedure employing KNO3, KF, Na4P2O7,
      EDTA and HNO3. The results show that the bioleaching process affected the
      partitioning of Mn and Zn, increasing its percentage of elution in the KNO3
      fraction while reducing it in the KF, Na4P2O7 and EDTA fractions. No significant
      effect was detected on the partitioning of Cu and Al. However, quantitatively the
      metals Mn, Zn, Cu and Al were extracted with higher efficiency after the
      bacterial activity. Titanium was unaffected by the bioleaching process in both
      qualitative and quantitative aspects.

PMID- 12188116
TI  - Microbial community dynamics during start-up of acidogenic anaerobic reactors.
AB  - Start-up of two acidogenic reactors under mesophilic (37 degrees C) and
      thermophilic (55 degrees C) conditions was carried out with methanogenic granular
      sludge as an inoculum and dairy wastewater as feed. During these 71 days of the
      start-up period, microbial community dynamics in these two acidogenic reactors,
      as monitored by denaturing gradient gel electrophoresis (DGGE) and dot-blot
      hybridization with group-specific oligonucleotide probes, was correlated to
      reactor performance. Due to pH drop to 5.5, DGGE community fingerprints for
      domains Bacteria and Archaea populations showed significant shifts after 13 days
      of operation, and this change was accompanied with an increase in volatile fatty
      acid production, a decrease in methane formation, and rapid sludge
      disintegration. Dot-blot hybridization results further indicated that the
      decrease in methane production was related to the decrease in Archaea population
      in particular with methanogens from 34.1% of total 16S-rRNA in the seed sludge to
      8% within the first 13 days, and to 2-5% at day 71. Among the methanogens
      monitored, the class Methanomicrobiales was the most abundant followed up by
      Methanobacteriales and Methanococcales. Due to an elevated temperature, the
      microbial community change was more significant and rapid in the thermophilic
      reactor than in the mesophilic reactor. Significant microbial population changes
      took place at the first 13 days for both reactors, but a longer period up to 71
      days was required to establish a microbial community with a stable metabolic
      activity.

PMID- 12188118
TI  - Kinetics of cadmium uptake by chitosan-based crab shells.
AB  - Crushed crab shells were chemically treated to transform the chitin present into
      chitosan. Three particle sizes with average diameters of 0.65, 1.43 and 3.38 mm,
      average pore diameters ranging from approximately 300 to 540 A, and a specific
      surface area of approximately 30 m2/g were obtained. Batch experiments were
      performed to study the uptake equilibrium and kinetics of cadmium by chitosan.
      Adsorption equilibrium followed a Freundlich relationship and was found to be
      independent of particle size indicating that adsorption takes place largely in
      the pore space. A high initial rate of cadmium uptake was followed by a slower
      uptake rate suggesting intraparticle diffusion as the rate-limiting step. The
      kinetic uptake data were successfully modeled using a pore diffusion model
      incorporating nonlinear adsorption. The effect of boundary layer resistance was
      modeled through inclusion of a mass transfer expression at the outside boundary.
      Two fitting parameters, the tortuosity factor (tau) and the mass transfer
      coefficient at the outside boundary (k(c)) were used. These parameters were
      unique for all solute and sorbent concentrations. The tortuosity factors varied
      from 1.5 for large particles to 5.1 for small particles. The mass transfer
      coefficient varied from 2 x 10(-7) m/s at 50 rpm to 2 x 10(-3) m/s at 200 rpm. At
      agitation rates below 100 rpm, boundary layer resistance reduced the uptake rate
      significantly. Its very high sorption capacity and relatively low production cost
      make chitosan an attractive sorbent for the removal of heavy metals from waste
      streams.

PMID- 12188117
TI  - Characterization of an acetate-degrading sludge without intracellular
      accumulation of polyphosphate and glycogen.
AB  - A sequencing batch reactor (SBR) was operated in the conventional anaerobic
      aerobic mode for enhanced biological phosphate removal (EBPR) using acetate as
      the sole substrate. Results showed that, however, the reactor was unable to
      remove phosphate from wastewater. The sludge containing 1.65% of phosphate did
      not exhibit the typical characteristics of polyphosphate-accumulating organisms
      (PAO) or glycogen-accumulating organisms (GAO). Phylogenetic analysis, based on
      16S rDNA sequences of individual microorganisms, showed that the microbial
      community of this acetate-degrading sludge was closely related to Comamonas
      testosteroni (43.8% of total population) of beta-1-proteobacteria, Zoogloea
      resiniphila (25.0%) of beta-2-proteobacteria, and Xanthomonas maltophilia (19.8%)
      of gamma-proteobacteria. Results of this study imply that GAO might not be the
      sole group of bacteria responsible to the deterioration of phosphate removal
      efficiency in an EBPR reactor.

PMID- 12188119
TI  - A risk assessment of pollution: induction of atrazine tolerance in phytoplankton
      communities in freshwater outdoor mesocosms, using chlorophyll fluorescence as an
      endpoint.
AB  - We investigated the validity and sensitivity of assessments of the induction of
      atrazine tolerance in freshwater outdoor mesocosmic phytoplankton communities,
      using the in vivo fluorescence of chlorophyll a as an endpoint, for monitoring
      ecotoxicology and for risk assessment programs applied to phytoplankton
      contaminated by photosystem II herbicides. Atrazine inhibits the photosynthetic
      process, and so the rise in in-vivo fluorescence could be used as a physiological
      manifestation of acute toxicity. Short-term tests (1 h) were used, in which
      increasing concentrations of the herbicide were applied to phytoplankton samples
      taken every two days from the mesocosms, and used to plot dose-response curves.
      The concentration at which atrazine increased the fluorescence by 25% relative to
      control samples was used to demonstrate the sensitivity of the phytoplankton, and
      the values found were compared for samples from different mesocosms (contaminated
      and non-contaminated). The taxonomic composition of the phytoplankton was also
      determined. The data showed that chronic exposure (25 days) to 30 microg/L of
      atrazine significantly increased the apparent tolerance of the phytoplankton to
      further contamination by the same compound. The use of in vivo fluorescence of
      chlorophyll a appears to be a reliable and effective parameter for monitoring the
      effects of atrazine pollution, and detecting the changes in community tolerance
      driven by pollution selection pressure.

PMID- 12188120
TI  - Oxidation of diazinon by anodic Fenton treatment.
AB  - Anodic Fenton treatment (AFT) is a new technology that has several advantages
      over classic Fenton treatment and electrochemical Fenton treatment. The oxidation
      of diazinon by AFT using different electrolytes has been investigated. NaCl, KCl
      and Na2SO4 show similar effects on the extent and rate of oxidation, and the data
      can be fitted quite well by the AFT kinetics model. Use of NaNO3 as the
      electrolyte causes low-efficiency electrolysis and a subsequent low oxidation
      rate for diazinon. The NaCl concentration level in the anodic half-cell and the
      concentration ratio between the two half-cells is optimized at 0.04M and 4:1
      (cathodic/anodic), respectively. The activation energy of diazinon oxidation by
      anodic Fenton treatment is estimated to be 12.6 +/- 0.6 kJ mol(-1), which is less
      than half of that for aqueous chlorine treatment. Diazoxon is the intermediary
      oxidation product. The oxidation of diazinon as a formulated product has also
      been investigated. Its dissipation kinetics can also be fitted quite well by the
      AFT model. Compared with the oxidation of pure diazinon, the oxidation rate of
      formulated diazinon is much lower, an indication that many formulation
      ingredients compete with diazinon for reaction with the hydroxyl radical.

PMID- 12188121
TI  - A simple empirical model for activated sludge thickening in secondary clarifiers.
AB  - A simple empirical model for the thickening function of the activated sludge
      secondary clarifiers is presented. The proposed approach relies on the
      integration of previous models and it is based on the phenomenon of dilution of
      the incoming activated sludge in the feeding well of the settling tanks. The
      method provides a satisfactory description of sludge stratification within the
      clarifier. The only requirements are limited to parameters which are readily
      incorporated into the routine analysis performed in an activated sludge plant,
      thereby eliminating the need for additional experimental or computational effort.
      The method was tested in a full-scale activated sludge plant and it was found
      that it describes fairly well the return sludge concentration, the diluted sludge
      blanket concentration, the sludge blanket solids concentration and the sludge
      blanket height of full-scale secondary clarifiers.

PMID- 12188122
TI  - Toxicity of linear alkylbenzene sulfonate in anaerobic digestion: influence of
      exposure time.
AB  - The inhibition of anaerobic digestion by the anionic surfactant linear
      alkylbenzene sulfonate was studied. The development of bacterial activity during
      several weeks was monitored by performing batch degradation tests with acetate
      and propionate. In the first phase the decay of activity without surfactant
      addition was studied. After the addition of the surfactant an immediate
      inhibition was detected. Subsequently, the degradation activity continued to
      decrease with increasing exposure time. Both, the immediate inhibition and the
      rate of the subsequent decrease of activity were dependent on the surfactant
      concentration. A kinetic model is presented that describes this behavior. A
      surfactant concentration of 14 mg L(-1) causes a 50% immediate inhibition of
      acetate degradation (27 mg L(-1) in the case of propionate degradation).
      Additionally, each 12 mg L(-1) of surfactant increases the decay rate of acetate
      degradation activity by a factor 10 (23 mg L(-1) for propionate degradation). A
      deviation from this model occurs at low surfactant concentrations (<3 mg L(-1)),
      where a slight stimulation of bacterial activity was observed. The above
      mentioned concentrations refer to measured surfactant concentrations. These were
      substantially lower than the nominal concentrations (added surfactant per
      volume). This discrepancy is explained by adsorption of the surfactant to the
      biomass. Finally, the importance of the presented kinetic model and the
      significance of surfactant toxicity for anaerobic digestion are discussed.

PMID- 12188123
TI  - Microwave-induced pyrolysis of sewage sludge.
AB  - This paper describes a new method for pyrolyzing sewage sludge using a microwave
      furnace. It was found that if just the raw wet sludge is treated in the
      microwave, only drying of the sample takes place. However, if the sludge is mixed
      with a small amount of a suitable microwave absorber (such as the char produced
      in the pyrolysis itself) temperatures of up to 900 degrees C can be achieved, so
      that pyrolysis takes place rather than drying. Microwave treatments were also
      compared with those carried out in a conventional electric furnace, as well as
      the characteristics of their respective carbonaceous solid residues.

PMID- 12188124
TI  - The relationship between TOX formation and spectral changes accompanying
      chlorination of pre-concentrated or fractionated NOM.
AB  - The change in the absorbance upon chlorination (the differential absorbance, AA)
      of natural organic matter (NOM) that has been concentrated, isolated, and/or
      fractionated from five sources was explored as a possible indicator of the
      formation of total organic halogen (TOX) in the samples. The results demonstrate
      that concentration and isolation of NOM using techniques that are currently in
      widespread use does not significantly alter the TOX-deltaA272 relationship that
      applies to the unprocessed NOM. However, when such samples are fractionated, the
      TOX-deltaA272 relationships for the different fractions are not identical. In
      particular, when the hydrophobic and hydrophilic neutral fractions of NOM are
      chlorinated, the amount of TOX formed per unit of A272 destroyed is significantly
      larger than the corresponding value for other NOM fractions. This observation
      might reflect the relatively high content of proteins and other amino acid
      structures that can be disinfection by-product precursors but that absorb little
      or no light at 272 nm.

PMID- 12188125
TI  - Correlations between differential absorbance and the formation of individual
      DBPs.
AB  - This study examined correlations between the differential absorbance at 272nm
      (deltaA272) and the formation of disinfection by-products (DBPs) in chlorinated
      water from the Tolt River, a water source for Seattle, WA. The DBPs investigated
      included chloroform (CHCl3), dichlorobromomethane (CHCl2Br), mono-, di- and
      trichloroacetic acids (MCAA, DCAA, and TCAA, respectively), chloral hydrate (CH),
      dichloroacetonitrile (DCAN) and 1,1,1-trichloropropanone (TCP). Whereas the
      kinetics of DBP formation are complex and are non-linear, the same DBP data
      represented as a function of deltaA272 are quite simple. Absorbance decreases
      when the water is chlorinated, i.e., deltaA272 is always negative. The DBP vs. 
      deltaA272 correlations can almost always be quantified by linear equations, at
      least above some threshold value of -deltaA272, with R2 values > 0.95. The only
      DBP that did not follow this trend was CH, for which an exponential relationship
      better described the data. TCP and DCAN were unstable at pH 7 and 8, but at pH 6
      linear correlations between their concentrations and -deltaA272 were as strong as
      those for the more stable DBPs. The threshold -deltaA272 value is approximately
      the same for many of the DBPs studied, supporting the hypothesis that individual
      DBPs are released following the formation of a common intermediate, or at least a
      small group of similar intermediates. The DBP vs. -deltaA272 correlations may
      have practical value since they provide an alternative approach for monitoring
      the formation of individual DBP species on-line, but the generality of the
      relationships needs to be further examined.

PMID- 12188126
TI  - Optimised immunofluorescence procedure for enumeration of Cryptosporidium parvum
      oocyst suspensions.
AB  - The aim of this study was to evaluate an optimised immunofluorescence assay in
      terms of the variability of sets of counts for Cryptosporidium parvum oocyst
      suspensions and data recovery and the reliability of the procedure. A coefficient
      of variation (CV) of 10% was determined to be the maximum value acceptable for
      count variability. It was found that the optimised IFA tested provided a high
      precision for the sets of enumerations for suspensions containing 800-20,000
      oocysts/mL. The procedure was found to be robust and providing high recovery
      level (96.3%). In terms of counting precision, the technique described here
      approaches the performance of flow cytometry and surpasses other manual
      techniques with a CV of 10% for a concentration close to 800 oocysts/mL. The
      procedure described is particularly suitable for the production of seed doses and
      for other applications requiring the titration of oocyst suspensions with a high
      degree of precision and accuracy.

PMID- 12188127
TI  - Faecal coliforms and faecal streptococci community in the underground water in an
      equatorial area in Cameroon (Central Africa): the importance of some
      environmental chemical factors.
AB  - A bacteriological and chemical study was carried out within 1 year on spring and
      well water of Yaounde. It assessed the importance of some chemical factors on
      some faecal bacterial communities. The monthly average densities of faecal
      coliforms and faecal streptococci varied, respectively, from 1 to 72 x 10(2) CFU
      100 ml(-1), and from 1 to 31 x 10(2) CFU 100 ml(-1) of water. These bacterial
      abundances undergo spatio-temporal fluctuations. These spring and well waters
      which are slightly bicarbonate, are acidic, soft, with low to average
      mineralisation. Most of the chemical characteristics of these waters are
      relatively stable with time, with respect to apparent spatial fluctuations. The
      degree of correlation between chemical parameters and the abundance dynamics of
      isolated bacteria is heterogeneous. In an artificially constituted spring
      biotope, the increase in pH, electrical conductivity, concentration of dissolved
      oxygen, chloride, sodium, potassium, calcium and magnesium favoured (P<0.01) the
      abundance of faecal coliforms and faecal streptococci. The high concentration of
      dissolved CO2 reduces (P<0.001) the abundances of these bacteria. They would
      nevertheless have developed such a mechanism allowing to minimise inhibitory
      effects of some environmental factors. In the well water, the ecology of faecal
      streptococci and faecal coliforms undergoes a relative instability, probably due
      to the variability of the resultant interaction network.

PMID- 12188128
TI  - Use of bituminous coal for concentration of enteroviruses from sewage and
      effluent.
AB  - A method has been developed for concentration of enteroviruses from untreated and
      treated domestic wastewater using bituminous coal bed as a virus adsorbent. A bed
      made from 1.5 g of 120 mesh coal powder was used for concentrating enteroviruses
      from 100 ml of clarified sewage at different pH values with and without addition
      of AlCl3. To enhance the adsorption of viruses, requisite quantities of aluminium
      chloride were added so that a final concentration of 0.0005 M could be achieved.
      At pH 3.0 maximum adsorption (82.8%) of poliovirus type 1 from artificially
      contaminated clarified sewage was observed without addition of AlCl3. However, at
      pH 5.0 maximum virus adsorption of 98.7% was achieved after addition of aluminium
      chloride. An average recovery of 86.9% of adsorbed viruses at pH 5.0 was achieved
      from coal bed with 3% flocculating beef extract at pH 9.5. This method for
      concentration of enteroviruses incorporating use of coal was compared with that
      of Millipore membrane filter method applied to raw sewage and clarified sewage.
      The results obtained from the methodology using coal as adsorbent was subjected
      to Student's "t" test and it was observed that its efficiency is confirmed for
      recovery of enteroviruses from raw and nonclarified sewage. These results are
      also comparable with that obtained with MF method. The results presented in this
      paper are indicative of the potential of this method for both treated and raw
      sewage.

PMID- 12188129
TI  - Effects of C18 long chain fatty acids on glucose, butyrate and hydrogen
      degradation.
AB  - The effects of linoleic (C18:2), oleic (C18:1), and stearic (C18:0) acids on
      glucose, butyrate and hydrogen degradation were investigated at 21 degrees C
      using a culture unacclimated to long-chain fatty acids (LCFAs). Diethyl ether was
      used to facilitate precise addition of LCFAs and provide adequate dispersion in
      cultures. Butyrate degradation was affected by diethyl ether but minimal effects
      were observed on hydrogen and glucose consumption. In the presence of oleic and
      stearic acids, the glucose consumption rate was similar but was approximately 50%
      lower in the presence of linoleic acid. The effect of a mixture of 100 mg l(-1)
      of each individual LCFA (300 mg l(-1) total LCFA) was approximately the same as
      100 mg l(-1) linoleic acid alone, suggesting no synergistic inhibition of glucose
      degradation. Butyric acid degradation was more severely inhibited by the LCFAs
      with inhibition becoming more severe with the addition of double bonds to the
      LCFA. Furthermore, mixtures of LCFAs synergistically inhibited butyric acid
      degradation compared to the results with individual LCFAs. In contrast, although
      lower hydrogen consumption rates were observed in cultures receiving oleic and
      linoleic acids compared to cultures receiving stearic acid, inhibition by all
      three acids individually or in mixture was limited. The introduction of LCFAs
      into a system may severly inhibit intermediate acid degradation while having
      little effect on acid production.

PMID- 12188130
TI  - Cyanobacteria-mediated internal eutrophication in shallow Lake Balaton after load
      reduction.
AB  - Nutrient loads to large, shallow Lake Balaton have been reduced by 45-50% since
      mid-1980s. While a delayed, but still surprisingly fast recovery was observed in
      the hypertrophic western areas of the lake, eutrophication followed sewage
      diversion from the mesotrophic northern basins. We assessed factors that could
      lead to this unusual response. The prime reason of the observed biomass increase
      might be a trend of increasing mean water temperature during late summers and the
      concurrent invasion of the subtropical cyanobacterium, Cylindrospermopsis
      raciborskii with superior light and nutrient utilisation capabilities. In the
      mesotrophic areas, the prerequisite of the unforeseen success of C. raciborskii
      was the exceptionally high potential of this species to generate internal P load.
      Specific morphometric features of the lake rather than nutrient loads might
      substantiate the increasing dominance of the cyanobacterium in these areas. Our
      results stress the need to consider individual characteristics of aquatic
      ecosystems during eutrophication management.

PMID- 12188131
TI  - Electrochemical removal of p-nonylphenol from dilute solutions using a carbon
      fiber anode.
AB  - p-Nonylphenol, which is widely used as raw material in industrial activities has
      been regarded as an environmental endocrine disrupter. In an effort to develop a
      new treatment method for p-nonylphenol, we initially investigated the
      electrochemical behavior of p-nonylphenol by voltammetric techniques. The
      electrochemical oxidation of p-nonylphenol led to the formation of
      electropolymerized film on the glassy carbon electrode surface. The fouling on
      the electrode surface by the electropolymerized film was evaluated by monitoring
      the electrode response of ferrocyanide ions as the redox marker. The
      electrochemical removal of p-nonylphenol based on the formation of the
      electropolymerized film on an anode surface was performed using a carbon fiber
      (CF) with a very large surface area. The high removal efficiency for p
      nonylphenol was obtained by applying a potential at 0.7 V. The maximum surface
      coverage of electropolymerized p-nonylphenol on the CF was about 5 x 10(-9)
      mol/cm2. The presence of humic acid hardly inhibited the removal of p
      nonylphenol. Furthermore, the application to the removal of phenol, o
      chlorophenol, p-chlorophenol, 2,4-dichlorophenol, and 2,4,5-trichlorophenol was
      attempted by using this method.

PMID- 12188132
TI  - Improved brine recycling during nitrate removal using ion exchange.
AB  - Ion exchange technology is currently the best for removing nitrate from drinking
      water. However, problems related to the disposal of spent brine from regeneration
      of exhausted resins must be overcome so that ion exchange can be applied more
      widely and economically, especially in small communities. For this purpose, a
      novel spent brine recycling system using combined biological denitrification and
      sulfate reduction processes was developed for more efficient reuse of brine. A
      granular activated carbon (GAC) adsorption column was introduced as an additional
      step to prevent contamination of resins by bio-polymers and dissolved organics
      present in the bio-reactor effluent. Two upflow sludge blanket reactors (USBRs)
      were operated in series for 166 days to provide denitrification and sulfate
      reduction. The denitrification reactor provided a nitrate removal efficiency of
      96% at a nitrate-N loading rate of 5.4 g NO3(-)-N/l d. The sulfate reduction
      efficiency of the sulfate reduction reactor remained approximately 62% at a
      sulfate loading rate of 1.8 g SO4(2-)/l d. Five ion exchange columns containing
      A520E resins were repeatedly operated in up to 25 cycles of service and
      regeneration using five kinds of brine: one virgin 3% NaCl and four differently
      recycled spent brines. Throughput decreased remarkably when the biologically
      recycled brine was not treated with the GAC column, probably due to the presence
      of bio-polymers and dissolved organic compounds. The sulfate reduction reactor
      placed after the denitrification step increased the bicarbonate concentration,
      which could be used as a co-regenerant with chloride. The inclusion of the
      sulfate reduction reactor into the conventional brine recycling system allowed
      more efficient reuse of brine, resulting in both reduced salt consumption and
      brine discharge.

PMID- 12188133
TI  - Effect of chromium(VI) on bacterial kinetics of heterotrophic biomass of
      activated sludge.
AB  - The effect of hexavalent chromium, Cr(VI), on the maximum specific growth rate,
      mu(m) and biomass yield, Y(H), of heterotrophic biomass was studied in batch
      tests conducted under high (= 10) and low (= 1.5) substrate-to-biomass ratios
      (S0/X0). The effects of sludge age and biomass acclimatization to Cr(VI) on the
      bacterial kinetics were also studied. The mu(m) values were determined by
      measuring oxygen uptake rate (OUR) and volatile suspended solids (VSS) increase.
      Cr(VI) concentrations equal or greater than 10 mg l(-1) inhibited the growth of
      unacclimatized activated sludge and caused a significant decrease in mu(m) and
      Y(H) values. The acclimatization of biomass and the selection of a high operating
      sludge age reduced the inhibitory effect of Cr(VI). At a sludge age of 20 days,
      Cr(VI) concentrations of <10 mg l(-1) stimulated bacterial growth as evidenced by
      an increase in both the mu(m) and Y(H) values. Determining mu(m) values by OUR
      and VSS methods, revealed that the presence of Cr(VI) in unacclimatized biomass
      caused an inhibitory effect mostly on substrate oxidation, while in acclimatized
      biomass, anabolic pathways were inhibited more.

PMID- 12188134
TI  - Modeling of photodecoloration of azo dye in a cocktail photolysis system.
AB  - The modeling of photodecoloration of a nonbiodegradable azo dye, Reactive Red 2
      (RR2), in a cocktail mixture of acetone (ACE) and triethylamine (TEA) solution,
      was investigated. It was found that the cocktail photolysis system was capable of
      completely decolorizing the azo dye in a very short treatment time, and the
      overall dye degradation followed pseudo-first-order decay kinetic. Three distinct
      stages were observed in the cocktail photolysis profiles. A lag phase was
      observed at the commencement of the degradation, but its duration was gradually
      reduced with the increment of the TEA concentration and the incident light
      intensity. Subsequently, a fast decay of RR2 was observed, in which over 80% of
      the dyes were reduced and it was interesting to find a tailing stage after 90-95%
      of the color was removed. A quantitative estimation of RR2 in the cocktail
      photolysis system was also studied. The differential equation consisting of two
      parallel reactions was solved to predict the concentration of RR2 at any reaction
      time with very good agreements. Furthermore, the sensitivity analysis indicated
      that the photosensitization process (contributed by ACE) was the dominant
      mechanism in the cocktail photolysis system, while the presence of a hydrogen
      source (TEA) did not contribute a major decay pathway but promoted the reaction
      rate of photosensitization by offering an add-on effect.

PMID- 12188135
TI  - EPR investigation on the efficiency of hydroxyl radical production of gamma
      irradiated anatase and bentonite.
AB  - Anatase and bentonite were treated by gamma rays in various conditions, and the
      change of the catalysts was characterized by electron paramagnetic resonance
      spectroscopy. Anatase gave four peaks with g(parallel) = 1.951 g(perpendicular) =
      1.973, g = 1.992 and 2.005. The height of the four peaks was directly
      proportional to the efficiency of hydroxyl radical production, and anatase
      treated by gamma rays in alkaline condition showed the most efficient production.
      Bentonite gave a peak with g = 2.005. In contrast to anatase, the peak height was
      inversely proportional to the efficiency of hydroxyl radical production, and non
      treated bentonite was the most efficient catalyst. Furthermore, the efficiency of
      hydroxyl radical production of the catalysts significantly influenced the
      decomposition of trichloroethylene and perchloroethylene by gamma rays.

PMID- 12188137
TI  - Performance of nanofiltration for arsenic removal.
AB  - Performance of rapid sand filtration inter-chlorination system was compared with
      nanofiltration (NF) to reduce the arsenic health risk of drinking water. It was
      found that rapid sand filtration with inter-chlorination is not effective in
      removing arsenic. If total arsenic concentration in raw water is below 50
      microg/L regardless of the turbidity of raw water, arsenic can be removed below
      WHO guideline value of 10 microg/L by conventional coagulation (polyaluminum
      chloride dosage is about 1.5 mg Al/L). However, if the raw water arsenic
      concentration exceeds 50 microg/L, more coagulant dosage or enhanced coagulation
      is needed. To adopt optimum coagulant dosage for arsenic removal, it needs to
      monitor raw water arsenic concentration, but it is difficult because arsenic
      measurement is time consuming. In addition, if raw water contains As(III), it is
      difficult for rapid sand filtration inter-chlorination system to meet an arsenic
      maximum contaminant level of 2 microg/L, which would achieve reduction of cancer
      risk below 10(-4). On the other hand, the NF membrane (NaCl rejection 99.6%)
      could remove over 95% of As(V) under relatively low-applied pressure (< 1.1 MPa).
      Furthermore, more than 75% of As(III) could be removed using this membrane
      without any chemical additives, while trivalent arsenic could not be removed by
      rapid sand filtration system without pre-oxidation of As(III) to As(V). Because
      both As(V) and As(III) removals by NF membranes were not affected by source water
      composition, it is suggested that NF membrane can be used in any types of waters.

PMID- 12188136
TI  - Bacteriophages isolated from activated sludge processes and their polyvalency.
AB  - In this study, bacteriophages were isolated from activated sludge and their host
      range was studied. Bacterial isolates were obtained from an activated sludge
      process treating urban sewage, and bacteriophages were obtained by plaque assay
      using the bacterial isolates obtained in this study as the host. Out of 15
      bacteria isolated, 9 supported plaque formation. The host range test was
      conducted with a combination of 8 bacteriophage isolates and 9 bacterial
      isolates. All of the 8 bacteriophages tested were found to form plaques on more
      than 1 host, and 4 of them formed plaques on both gram-positive and gram-negative
      bacterial isolates. Three of the 8 bacteriophages failed to form plaques on their
      original bacterial host. The experimental result indicates that bacteriophages
      are an active part of the activated sludge microbial ecosystem, having a very
      close ecological relationship with their host bacteria.

PMID- 12188138
TI  - Biodegradation of oxo-alcohol ethoxylates in the continuous flow activated sludge
      simulation test.
AB  - Biodegradation of two alpha-methyl branched oxo-alcohol ethoxylates (OAE) of
      different polydispersity: LIAL 125/14 BRD (LIALB) (broad M.W. distribution) and
      LIAL 125/14 NRD (LIALN) (narrow M.W. distribution), both having an average of 14
      oxyethylene subunits (EO) and a C(12-15) alkyl moiety were tested under the
      continuous flow activated sludge conditions of the classical Husmann plant.
      Primary biodegradation and concentration of metabolites: free oxo-alcohol
      fraction (FOA) and poly(ethylene glycols) (PEG), were measured. PEG were divided
      into two fractions: short-chained PEG (PEGshch) (1-4 EO) and long-chained PEG
      (PEGlch) (>4 EO). The indirect tensammetric technique combined with an adequate
      separation was used for analysis. Central fission was found to be a highly
      dominating pathway, as is the case with fatty alcohol ethoxylates. OAE are highly
      primarily biodegraded (above 95%). High concentrations of FOA and PEG are formed.
      Once formed the PEGlch are further fragmented into the PEGshch. Free alcohol
      fraction compounds are biodegraded sooner when alkyl moiety is shorter. OAE
      polydispersity has an influence on the kinetics of biodegradation; PEG formed
      from LIALN are biodegraded slower and to a lower degree than those from LIALB.

PMID- 12188139
TI  - Treatment of a colored groundwater by ozone-biofiltration: pilot studies and
      modeling interpretation.
AB  - Pilot studies investigated the fates of color, dissolved organic carbon (DOC),
      and biodegradable organic matter (BOM) by the tandem of ozone plus biofiltration
      for treating a source water having significant color (50 cu) and DOC (3.2 mg/l).
      Transferred ozone doses were from 1.0 to 1.8 g O3/g C. Rapid biofilters used
      sand, anthracite, or granular activated carbon as media with empty-bed contact
      time (EBCT) up to 9 min. The pilot studies demonstrated that ozonation plus
      biofiltration removed most color and substantial DOC, and increasing the
      transferred ozone dose enhanced the removals. For the highest ozone dose,
      removals were as high as 90% for color and 38% for DOC. While most of the color
      removal took place during ozonation, most DOC removal occurred in the biofilters,
      particularly when the ozone dose was high. Compared to sand and anthracite
      biofilters, the GAC biofilter gave the best performance for color and DOC
      removal, but some of this enhanced performance was caused by adsorption, since
      the GAC was virgin at the beginning of the pilot studies. Backwashing events had
      no noticeable impact of the performance of the biofilters. The Transient-State,
      Multiple-Species Biofilm Model (TSMSBM) was used to interpret the experimental
      results. Model simulations show that soluble microbial products, which comprised
      a significant part of the effluent BOM, offset the removal of original BOM, a
      factor that kept the removal of DOC relatively constant over the range of EBCTs
      of 3.5-9 min. Although improved biofilm retention, represented by a small
      detachment rate, allowed more total biofilm accumulation and greater removal of
      original BOM, it also caused more release of soluble microbial products and the
      build up of inert biomass in the biofilm. Backwashing had little impact on
      biofilter performance, because it did not remove more than 25% of the biofilm
      under any condition simulated.

PMID- 12188140
TI  - Sulphadimethoxine and Azolla filiculoides Lam.: a model for drug remediation.
AB  - Plants can be an interesting tool for in situ remediation of drug contaminated
      waters. In a laboratory model Azolla filiculoides Lam., an aquatic fern known to
      absorb pollutants, has been exposed to an environmental persistent antibiotic
      commonly used in intensive farming, sulphadimethoxine (S), to test its
      bioremediation capability. In a 5 week experiment, plants were cultivated outdoor
      at four drug concentrations (50, 150, 300 and 450 mg l(-1)) in N-free mineral
      medium. Drug affects growth rate (as biomass yield per week), N2-fixation,
      heterocyst frequency, but plants are able to survive. Notwithstanding, at all
      concentrations tested drug was actively removed from the medium and the
      accumulation in the biomass is in order of magnitude up to mg g(-1) plant dry
      weight (1000 ppm). Drug uptake and degradation rates increase with S
      concentrations in the culture medium. The efficacy of the model was very high.
      These results demonstrated that Azolla can be taken into consideration as a tool
      for sulphonamides environmental monitoring and decontamination.

PMID- 12188141
TI  - Metal ion complexation properties of fulvic acids extracted from composted sewage
      sludge as compared to a soil fulvic acid.
AB  - Complexation properties of an anthropogenic fulvic acid (FA) extracted from a
      composted sewage sludge (csFA) for Cu(II), Pb(II) and Cd(II) were studied at pH=6
      and at a concentration of 25 mg L(-1). For the case of Cu(II), a particular
      analysis of the complexation phenomena was done at pH values of 3, 4, 5 and 6 and
      at aqueous FA concentrations of 25, 50 and 100 mg L(-1) by synchronous excitation
      molecular fluorescence spectroscopy (SyF). Potentiometric titrimetry with Cu(II),
      Pb(II), Cd(II) and H+ ion-selective electrodes and acid-base conductimetric
      titrations were used to obtain experimental information about the acid properties
      and complexation phenomena. A comparison of the results obtained for csFA with a
      natural soil FA (sFA) was made. Differences have been detected in the structural
      composition of the two samples and in the structure of the binding sites. In the
      csFA, binding site structures containing nitrogen probably play an important role
      in the complexation, besides oxygen containing structures. Complexation by sFA is
      mainly due to carboxylic and phenolic structures. Nevertheless, this work shows
      that csFA have macroscopic complexation properties (magnitude of the conditional
      stability constant and binding sites concentration) somewhat similar to the
      natural sFA samples.

PMID- 12188142
TI  - Survival of an Aeromonas hydrophila in an artificial mineral water microcosm.
AB  - The survival capacity of an Aeromonas hydrophila strain (named SB14) isolated
      from mineral water was investigated in an artificial mineral water microcosm. The
      bacterial count of this microorganism was compared with two strains of other
      species from aquatic environments (Pseudomonas fluorescens SSD and Pseudomonas
      putida SSC) and a bacterium indicative of faecal pollution (Escherichia coli ATCC
      25922). Among the strains, all added to sterile Pyrex glass flasks (1 l) to yield
      a final bacterial count of about 5 x 10(6) CFU/ml, A. hydrophila SB14 showed a
      quite strong survival capacity (150 days), even though the Pseudomonas strains
      were better adapted to this habitat (more than 240 days). E. coli ATCC 25922 was
      the least well fitted to survive and was no longer detected after 70 days. When
      A. hydrophila SB14 was inoculated together with one or two of the above strains,
      its survival appeared to be dependent on interaction with other organisms. A
      marked decrease in survival by 30 days, possibly due to antagonistic interaction,
      was observed when this microorganism was associated with E. coli ATCC 25922, and
      an increase by 30 and 60 days, possibly due to commensalic interaction, was
      obtained when A. hydrophila SB14 was inoculated with P. fluorescens SSD or P.
      putida SSC, respectively.

PMID- 12188143
TI  - Comment on "Permeability of fractal aggregates".

PMID- 12188144
TI  - Cultivating spiritual intelligence to heal diseases of meaning.

PMID- 12188145
TI  - Challenges for spiritual care-giving in the millennium.

PMID- 12188146
TI  - Community mental health care: documenting the role of the nurse.
AB  - In Australia, the process of deinstitutionalisation has resulted in the closure
      or downsizing of many large stand-alone psychiatric hospitals. The aim of modern
      community mental health care is to provide treatment and rehabilitation for
      people, who have a mental illness, in their local community. This aim is
      supported by the Australian National Mental Health Strategy that outlines the
      importance of health professionals, carers, and consumers working together to
      obtain the best therapeutic outcomes. This study was undertaken to obtain
      information regarding the current role of the community mental health nurse
      (CMHN). All community mental health nurses working in the Adult Program at the
      Directorate of Mental Health Services, Fremantle Hospital and Health Service in
      Western Australia participated in the study. The study was completed in November
      2000. The results showed that the CMHNs' role focused on six main areas. These
      areas included the day-to-day management of clients, working with carers and
      their families; crisis work for both existing andfirst time contacts; as well as
      liaison and advocacy work. Thefinding of this study demonstrate CMHN's work most
      often with acutely ill and psychotic patients and theirfamilies. Therefore,
      CMHN's play a pivotal role in promoting and sustaining the philosophy of
      community mental health care. In addition, the liaison work within the community
      completed by CMHN's is vital to address the mental health needs of the community
      and to reduce the stigma associated with mental illness. The documentedfindings
      of this study provide challengesfor thefurther expansion of the CMHN's role and
      the development of best practice initiatives in community mental health care.

PMID- 12188147
TI  - Contextualising the appraisal of Self-care Agency Scale in Hong Kong.
AB  - Published reports on the use of the Appraisal of Self-care Agency (ASA) Scale
      among Chinese people are scarce, the procedure of testing the ASA Scale is thus
      necessary before it is used clinically on Chinese population. The objective of
      this study was to test the validity and reliability of the ASA Scale on the
      Chinese population. Qualitative and quantitative approaches were adopted in
      testing the Scale. A panel of 4 experts was invited to examine the content of the
      Scale and 128 elderly peoplefrom 3 elderly centers in Hong Kong were employed to
      examine its construct validity. Item analysis was conducted using Cronbach's
      Alpha coefficient to examine the reliability of the Scale. Content validity index
      of 0.88 was achieved resultingfrom the assessment of the 4 experts. Sevenfactors
      were extracted from the factor analysis representing approximately 70% of
      variance. The reliability coefficient for the entire Scale was 0.72. It was
      evident that the ASA Scale was a valid and reliable research instrumer that can
      be used in the Chinese communities.

PMID- 12188148
TI  - Patterns of knowing in professional practice in dealing with the abuse of older
      people.
AB  - The abuse of older people by someone they know and should be able to trust is a
      complex problem thatfaces nurses working in aged care. From the beginning days of
      dealing with this social problem, a great deal has been learned about elder
      abuse, about victims and perpetrators and about the difficulty of working in this
      area. A conceptual framework of knowing, such as that developed by Barbara Carper
      (1978), is a valuable framework to guide knowledge organisation and utilisation
      in confronting cases of abuse in clinical practice. This article briefly
      considers Carper's four ways of knowing to show how they can influence
      professional practice in general, and dealing with elder abuse in particular.

PMID- 12188149
TI  - The complexities of interviewing Italo-Australian men about sensitive health
      issues.
AB  - The increase in the incidence of prostate cancer in Australia has been followed
      by an increase in prostate cancer awareness among Australian adults. However,
      men's level of knowledge on the subject has never been systematically assessed
      (Laws et al, 2000). It was postulated by Laws et al., (2000) that many men from
      Non English Speaking Cultures (NESC) experience language and cultural
      difficulties that would ultimately impinge on their ability to access information
      about prostate problems. In exploring 'The knowledge and attitudes of Italo
      Australian men toward prostate cancer' the researchers became aware that the
      majority of interviewees (n=20) were reluctant to divulge information on all
      aspects of the topic (Drummond et al., 2001). This report highlights the
      importance of using a reflexive phase within the research process as a means of
      identifying factors that can, in part, explain the paucity of data and act a
      basis for developing strategies to overcome the problem. The research
      subsequently evolved to incorporate a secondary research question. 'Why were the
      men at interview so reluctant to speak of general health problems and health
      problems related to prostatic dysfunction?' A focus group comprised of Italo
      Australian men was used to explore gender and culturalfactors, perceived by the
      researchers as, restricting theflow of information. Several barriers thought to
      be limiting the release of information were confirmed. We conclude that our
      findings will have implications for other researchers wanting to maximise their
      chances of accessing information rich datafrom the experiences of men from NESCs.

PMID- 12188150
TI  - Issues in adolescent health: a challenge for nursing.
AB  - The young people of today are the greatest investment we as adults have in our
      future. The care and nurturing we afford the adolescent is just as important as
      that which we afford to children or the elderly. Although most adolescents have a
      preoccupation with their bodies, they do not always engage in activities that
      will protect and develop them. Adolescents are often exposed to peer pressure,
      the effects of which may impact negatively on their behaviour and their health.
      Many adolescent health and behavioural issues evolve from developmental changes
      and can manifest in a confrontational attitude toward society, parents and
      others. They are hormonally 'fully charged', and their adolescent sexuality can
      have enormous effects on their future physical, psychosocial, moral and sexual
      development. Nurses have a pivotal role to play in ensuring children and
      adolescents learn the facts relating to the consequences of engaging in unhealthy
      behaviour and lifestyle. Nurses must also encourage parents to model and
      reinforce good health practices, such as serving balanced and nutritious meals at
      regular times and planning positive family activities. In this paper we review
      some of the salient issues in adolescent health today.

PMID- 12188151
TI  - Health for all Australians.
AB  - This paper explores some of the social and political factors that have influenced
      the way in which the Australian health care system has developed, and the models
      it uses to deliver health care. This information is used to suggest changes that
      need to be made to health policy and the health care system in order to provide
      equitable access and efficient service to all Australians. The example of persons
      who have contracted Hepatitis C via injecting drug use is used to illustrate the
      arguments.

PMID- 12188152
TI  - An oral history of Japanese nursing: voices of five senior nurses who have
      experienced nursing since the 1950s.
AB  - The history of nursing cannot be considered separately from the history of women.
      In this study the public history of nursing and women was re-explored via the
      lived voices of five senior nurses in Japan. An oral history method using in
      depth interviewing for data collection was used. Contemporary Japanese women's
      social position was constantly influenced by government policies from an
      historically androcentric society. Nursing, as a predominately female occupation,
      has also struggled with its position in society and in the hospital system. Data
      were categorised into five themes through the nurses' stories and analysed using
      feminist liberal theory. Findings from the current study showed that various
      elements of unequal opportunity to participate in society were an outcome of this
      history. Nursing in Japan appears to have been socialised without a relationship
      to feminism. Experiences of the participants in this study indicate a demand for
      the liberation of nurses as women. These participants wished nurses in Japan to
      focus on professionalism with an attitude which is independent of past
      androcentric policies and historical social inequities. With such an autonomous
      attitude, directions for nursing in Japan become constructive.

PMID- 12188153
TI  - An emancipatory praxis study of nursing students on clinical practicum in New
      Zealand: pushed to the peripheries.
AB  - The purpose of this qualitative study was to gain a better understanding of the
      learning experiences of nine nursing students on clinical placement in New
      Zealand. The students were in their third and final year of their baccalaureate
      nursing degree. The study specifically examined what impinged upon their learning
      experience in the clinical venue. Data was obtained from interviewing the
      students, initially individually and finally in a focus group. Themes emerged
      through words and concepts as the data was analysed. The themes included
      powerlessness; marginalization; the move from a holistic to a reductionist
      approach in care; the exploitation of minority students and the myth of praxis.
      Clinical practice was a time for nursing students to apply their knowledge to
      their practice, and to gain experience and confidence. Their clinical practice
      was normally a positive experience, but, each student spoke of the occasional
      negative episode. These left them with feelings of powerlessness and
      marginalization. The Maori students felt exploited. The students were concerned
      about the lack of time to debrief at the end of the day, and to share their
      experiences with their educator and colleagues. The students' negative
      experiences were often the result of a clinical practitioner's high workload,
      under resourcing and the nurse educator's unavailability. An emancipatory praxis
      methodology was used to guide the research and hence Habermasian critical theory
      underpinned this study. It has demonstrated within this research the necessityfor
      strategic action, by exposing the current situation to create an awareness for
      favourable change. The findings from this research will enable educators and
      clinical practitioners to have a clearer understanding of the needs of nursing
      students in clinical practice. Recommendations from this study included the need
      for further research into nursing students clinical supervision models, and the
      identication of the special learning needs of indigenous nursing students.

PMID- 12188154
TI  - Women, Hepatitis C, and sexuality: a critical feminist exploration.
AB  - Sexuality is a neglected subject in nursing with nurses often exhibiting
      erotophobia. Furthermore Hepatitis C is a stigmatised disease and people living
      with HCV frequently experience stigmatisation by health professionals, including
      nurses. Erotophobia and HCV related stigmatisation is detrimental to the
      formation of an open and trusting nurse-client relationship and is potentially
      injurious to the health and well being of people living with HCV who come into
      contact with nurses in the course of their illness. This research explored the
      question of whether living with HCV affected the sexuality of HCV positive women
      and if so in what ways?

PMID- 12188155
TI  - Introducing abdominal massage in palliative care for the relief of constipation.
AB  - Constipation and its associated problems affect approximately 50% of patients
      admitted to hospices in the United Kingdom. It is common practice in many
      hospices to offer a range of complementary therapies of which aromatherapy
      massage is one. Abdominal massage for the relief of constipation was once a
      commonly practised therapy but its use declined over time, like other
      complementary therapies there is now a rekindling of interest in the role that
      abdominal massage may play in relieving constipation. This paper will explain how
      a safe non-invasive easily learnt technique of abdominal massage was introduced
      in a palliative care setting to help relieve some of the problems associated with
      constipation. Despite the number of patients involved in this project being
      small, relief from some of the symptoms associated with constipation was
      experienced by some patients. A formal study of the benefits of abdominal massage
      in palliative care far the relief of constipation is needed.

PMID- 12188156
TI  - Education and training of complementary therapists: the role of higher education.
AB  - This paper is intended to inform the reader of key issues relating to education
      and training of complementary therapists. It discusses the role of higher
      education in the training of complementary therapists in light of changing policy
      and patterns of course delivery. It highlights the need for professional
      standards in clinical practice and for training underpinned by an evidence base.
      The paper presents the need for collaborative working with professions for
      complementary medicine, indicating some areas of good practice established at the
      University of Central Lancashire.

PMID- 12188157
TI  - Reiki.

PMID- 12188158
TI  - Primum non nocere: thoughts on the need to develop an 'adverse events' register
      for complementary and alternative therapies.
AB  - Building a body of knowledge to support the efficacy and practice of
      complementary and alternative therapies is an imperative that should be fully
      embraced by all those involved. Additional endeavours to monitor adverse events
      related to complementary and alternative therapies should also be pursued. The
      history and extent of medical iatrogenesis is briefly outlined, as is the
      literature on adverse events related to complementary and alternative therapies.
      Allopathic medicine is slowly realising the negative impact of iatrogenesis and
      is starting to develop systems to monitor such events in order to reduce or
      eliminate their existence. It is suggested that a similar development is needed
      in complementary and alternative therapies, so that it can be ensured that, at a
      minimum, primum non nocere, the therapy should firstly do no harm.

PMID- 12188159
TI  - Becoming a reflective nurse or midwife: using complementary therapies while
      practising holistically.
AB  - Complementary therapies augment nursing and midwidfery practice, but they do not
      necessarily make it holistic, nor is that practice guaranteed of being based on
      systematic reflection. This article argues the need for holistic nursing and
      midwifery to be based on reflective processes, enabling continual development and
      renewal of the person and practitioner. Practical hints are suggested to assist
      nurses and midwives in becoming reflective, thereby increasing the likelihood of
      incorporating complementary therapies while practising holistically.

PMID- 12188160
TI  - Clients' perceptions of the benefits of reflexology on their quality of life.
AB  - Awareness has increased among health-care professionals, patients and the general
      public of the importance of an holistic approach to cancer care. Psychosocial
      interventions, including complementary therapies, may help to improve the quality
      of life (QoL) of people with cancer by helping to reduce the distress associated
      with the diagnosis and treatment of cancer and by facilitating improved
      psychological adjustment to the experience of cancer. The following article
      presents anecdotal findings at ARC Cancer Support Centre Dublin, Ireland, of
      clients' perceptions of the benefits of reflexology interventions on their QoL.
      Reflexology interventions were perceived to impact positively upon clients'
      levels of impairment and functional status, including physical and psychological
      function, with implications for general health perceptions. The paper discusses
      how these findings might form the basis of further, more rigourous evaluation of
      the benefits of reflexology for people with cancer at ARC Cancer Support Centre.

PMID- 12188161
TI  - Herbal medicine in pregnancy.
AB  - The objective of the study was to assess the frequency of alternative medical
      usage in an antenatal population. A survey of alternative medicine usage was
      carried out among 305 consecutive patients over 2 months at their registration in
      mid-pregnancy at an Australian Antenatal Clinic. The study showed that something
      like 40% of patients used alternative medical therapy, including 12% herbal
      therapy. No specific study of pregnancy outcome was carried out, but it is of
      concern that some herbs taken had the potential to adversely affect pregnancy
      outcome. The herbal therapies commonly used in pregnancy are reviewed with their
      potential complications; examples of toxicity are also discussed. It is important
      to obtain a herbal medicine history at any time but particularly in pregnancy.
      Herbs may have unrecognised effects on pregnancy or labour, have interactions
      with prescribed medications and have potentially serious complications for the
      foetus.

PMID- 12188162
TI  - Aesthetics, postmodern nursing, complementary therapies and more: an Internet
      dialogue.
AB  - Electronic means of communication opens up whole new realms of possibilities.
      Whilst discussing how Jean Watson's new book and CD could be reviewed in perhaps
      more unconventional ways an idea slowly emerged that we could conduct an e-mail
      interview and talk about several of the many issues that are raised by both of
      these works of art. Over a period of several months during the years 2000 and
      2001, e-mails sped their way to and fro across the Atlantic, the interview soon
      took on a mind of itself. What follows is the emergent.

PMID- 12188163
TI  - The future of reflexology.
AB  - It would have been difficult 30 years ago to foresee how great would be the grass
      roots response to reflexology. Over the past 5 years public and professional
      interest in Complementary and Alternative Medicine (CAM), its practice, future
      development and possible regulation have been of much concern in many quarters,
      not least among therapists themselves. The report of the House of Lords Select
      Committee on Science and Technology into Complementary and Alternative Medicine
      published in November 2000 made a number of recommendations likely to influence
      the social framework in which CAM has been practiced. This paper offers an
      appraisal of the practice of reflexology, its historic development, legal issues,
      scope and limitations of practice.

PMID- 12188164
TI  - The House Of Lords Select Committee for Science and Technology. Their report on
      complementary and alternative medicine and its implications for reflexology. . .

PMID- 12188167
TI  - Measuring patient persistency with drug therapy using methods for the design and
      analysis of natural history studies.
AB  - The same methodologic rigor should be applied in measuring both patient
      persistency with drug therapy and the natural history of disease: Investigators
      should design natural history cohort studies and evaluate the resulting data
      using survival analysis. Although simpler analyses, such as those based on the
      medication possession ratio, may allow identification of obvious drug therapy
      patterns, results of survival analyses allow more refined interpretations that
      may help decision makers improve disease management in the population-based
      setting. This paper explains how to design persistency studies as natural history
      studies whose outcomes can be analyzed using survival analysis.

PMID- 12188166
TI  - An economic analysis of switching to latanoprost from a beta-blocker or adding
      brimonidine or latanoprost to a beta-blocker in open-angle glaucoma or ocular
      hypertension.
AB  - BACKGROUND: In treating patients with ocular hypertension or primary open-angle
      glaucoma, if a single agent cannot successfully control the pressure, additional
      medications may be prescribed. The cost of treatment may become expensive,
      especially with multiple drug therapy. Thus, prescribing techniques that help
      minimize costs may be beneficial to patients when medically appropriate.
      OBJECTIVE: To evaluate differences in drug and visit costs after switching to
      latanoprost 0.005% monotherapy (LM) versus adding latanoprost 0.005% once daily
      (Lbeta) or brimonidine 0.2% twice daily (Bbeta) in patients uncontrolled on beta
      blocker therapy alone. METHODS: This study included 148 consecutive qualified
      charts of open-angle glaucoma or ocular hypertension patients within the first
      year of follow-up after switching from beta-blocker monotherapy to latanoprost or
      adding latanoprost or brimonidine. RESULTS: The Bbeta group demonstrated the
      highest costs per month, followed by the Lbeta group, then the LM group. A trend
      existed in the Lbeta group to a lower pressure than the Bbeta or the LM groups. A
      greater mean change in medication per patient per month was seen in the Bbeta
      group compared to the latanoprost treatment groups. Additionally, a greater
      number of visits per month occurred in the Bbeta than in the LM and Lbeta groups.
      The Bbeta group also reported significantly more tearing and fatigue.
      CONCLUSIONS: This study suggests that in patients uncontrolled on beta-blocker
      therapy, switching to latanoprost, when medically appropriate, may provide a
      further mean reduction in intraocular pressure and save costs compared to adding
      latanoprost or brimonidine.

PMID- 12188168
TI  - Population-based persistency rates for topical glaucoma medications measured with
      pharmacy claims data.
AB  - BACKGROUND: Persistency with drug therapy reflects a number of factors, including
      patient tolerability of adverse events resulting from therapy and clinician
      satisfaction with the medication's effectiveness in reducing intraocular
      pressure. OBJECTIVE: This study assesses persistency with topical glaucoma
      medications administered as initial therapy by evaluating rates of
      discontinuation and change in therapy. METHODS: A retrospective cohort study was
      conducted using pharmacy claims data from 3 geographically diverse healthcare
      plans. Newly treated glaucoma patients younger than 65 years of age were selected
      based on an initial glaucoma medication fill during a 12-month period. Patients
      were followed for persistency, defined as discontinuation or change (switch or
      add-on) of initial glaucoma therapy; discontinuation of therapy was also
      evaluated as a separate end point. RESULTS: In all, 1330 patients (followed for
      1126 person-years) met the eligibility criteria. Compared with latanoprost users,
      patients initiated on other topical monotherapies were more likely to discontinue
      or change therapy, and patients initiated on other topical monotherapies were
      more likely than latanoprost users to discontinue therapy. CONCLUSION: Population
      based data indicate that latanoprost offers superior persistency compared to
      agents from other popular classes of topical ocular hypotensives.

PMID- 12188169
TI  - Rates of discontinuation and change of glaucoma therapy in a managed care
      setting.
AB  - BACKGROUND: Comparing discontinuation and change rates of glaucoma
      pharmacotherapies provides insight as to which agents perform more effectively.
      OBJECTIVE: To quantify the rates of discontinuation and change of different
      glaucoma therapies. METHODS: This retrospective, observational study using
      managed care administrative claims data included patients who were between 20 and
      64 years of age and received at least 1 prescription for 1 of the following
      glaucoma agents as monotherapy: betaxolol, brimonidine, latanoprost, or timolol.
      Patients receiving any glaucoma medication during the 180 days prior to their
      index prescription were excluded, as were those who did not have continuous plan
      enrollment during this period. The primary outcome measures were the
      discontinuation and change (switching/adding on) of the index glaucoma
      medication. Rates of discontinuation and change were compared using a
      proportional hazard model. RESULTS: A total of 1006 patients comprised the final
      study population. Approximately 62% of patients discontinued their index glaucoma
      medication, and 18% of patients changed to a different therapy within 18 months
      of starting therapy. Among those discontinuing therapy, latanoprost patients
      remained on therapy the longest (mean: 217 days) compared to other study cohorts
      (range: 182 to 184 days). Compared with latanoprost, patients initiated on any of
      the other agents were more likely to discontinue or change therapy. CONCLUSIONS:
      This study indicates that latanoprost therapy results in a lower rate of
      discontinuation or change compared to patients started on betaxolol, brimonidine,
      or timolol.

PMID- 12188171
TI  - Measuring persistency and intraocular pressure-controlled days in patients
      receiving topical glaucoma medications.
AB  - Investigators have developed methods to estimate the number of healthy days or
      symptom-free days in randomized trials or population-based settings. Such
      measures can be used in cost-effectiveness studies or disease management
      surveillance. This paper suggests that the concept can be extended to measure
      intraocular pressure (IOP)-controlled days in glaucoma by combining data from
      randomized trials on IOP control (ie, whether a target IOP or percent reduction
      in IOP was achieved) with data from pharmacy database studies on drug
      persistency. Patients with lower rates of persistency would be expected to
      experience fewer IOP-controlled days as they switch therapies or discontinue
      topical therapy altogether. Evaluating IOP-controlled days according to patients'
      topical glaucoma therapies could improve population-based disease management
      compared with the use of simpler measures that consider IOP measurements at a
      single point in time.

PMID- 12188170
TI  - Discontinuation rates of topical glaucoma medications in a managed care
      population.
AB  - BACKGROUND: Rates of medication discontinuation reflect factors including
      effectiveness, tolerability, cost, and dosing frequency. Discontinuation data can
      be useful to physicians and health plan managers as they compare various glaucoma
      medications. OBJECTIVE: To compare rates of discontinuation of therapy in
      patients initially prescribed monotherapy with a topical glaucoma medication.
      METHODS: Members of a managed care plan who filled at least 1 prescription for
      latanoprost, timolol, or brimonidine during a 30-month period were eligible to
      participate in this study. Prescription refill records for all glaucoma agents
      used in the plan were extracted for the study period. Rates of discontinuation of
      initial glaucoma therapy were compared using Cox regression methods; Kaplan-Meier
      survival curves were generated. RESULTS: A total of 72,744 prescriptions were
      eligible, of which 48491 were for study drugs. Latanoprost was the most
      frequently dispensed therapy (accounting for 49.7% of study drugs), followed by
      timolol (30.6%), and brimonidine (19.6%). After inclusion and exclusion criteria
      were applied, 2283 patients were included in analyses. Latanoprost-treated
      patients were significantly less likely to discontinue medication than were those
      treated with timolol or brimonidine. Kaplan-Meier survival curves confirmed that
      latanoprost-treated patients exhibited the greatest persistency with therapy.
      CONCLUSION: In this managed care setting, rates of discontinuation in patients
      initially treated with latanoprost were lower than those of patients receiving
      comparator drugs.

PMID- 12188172
TI  - Fluorescence in situ hybridization on sperm using alkaline denaturation.

PMID- 12188173
TI  - Tandem affinity purification of protein complexes from mammalian cells.

PMID- 12188174
TI  - In-gel analysis of site-specific rnases.

PMID- 12188176
TI  - Inhibitory effects of agarose gel and LB medium on DNA sequencing.

PMID- 12188175
TI  - Sequencing of difficult templates containing poly(A/T) tracts: closure of
      sequence gaps.

PMID- 12188177
TI  - Application of the recombination of beta-lactamase gene to PCR-based site
      directed mutagenesis.

PMID- 12188178
TI  - In vivo site-directed mutagenesis of yeast plasmids using a three-fragment
      homologous recombination system.

PMID- 12188180
TI  - Multi-photon microscopy: seeing more by imaging less.

PMID- 12188179
TI  - Deoxycholate-based Method to screen phage display clones for uninterrupted open
      reading frames.

PMID- 12188181
TI  - Cytoplasmic RNA extraction from fresh and frozen mammalian tissues.
AB  - The quality of collections of expressed sequence tags andfull-length cDNAs is
      adversely affected by the presence of "junk" clones derivedfrom unspliced or
      partially spliced RNAs present in conventional total RNA preparations. One can
      overcome this problem by using intact cytoplasmic RNA to create cDNA libraries,
      but the methods in the literature that describe the preparation of RNA only work
      well for extracting cultured cells. Cell lines are not as diverse as one would
      like, and to clone comprehensive sets of human and model organism full-length
      cDNAs, libraries have to be prepared from tissue samples. Thus, we have developed
      a robust and inexpensive method that allows intact cytoplasmic RNA to be
      extracted from both fresh and frozen mammalian tissues. A mouse full-length, cap
      trapped cDNA library prepared with RNA using this new procedure had excellent
      characteristics.

PMID- 12188182
TI  - Rapid generation of nested deletions by differential restriction digestion.
AB  - A method was devised for generating nested deletions in DNA that exploits the
      difference in frequency of restriction sites recognized by compatible restriction
      endonucleases. A cloning vector was constructed that contains no common blunt-end
      or RsaI restriction sites and two 8-bp blunt-end restriction sites flanking a
      commodious multiple cloning site. DNA fragments are cloned into the multiple
      cloning site using blue-white selection, and nested deletions are generated by
      digesting the resulting plasmid with either SwaI or PmeI and partially digesting
      the insert DNA with RsaI. The DNAs are ligated and transformed, producing afamily
      of plasmids with different-sized deletions. The DNA sequence of these inserts can
      be rapidly determined, and the overlapping sequences can be assembled in silico
      to produce a large DNA contig. Nested deletions generated in this manner can also
      be used for the structure-function analysis of proteins.

PMID- 12188183
TI  - Optimizing DpnI digestion conditions to detect replicated DNA.

PMID- 12188184
TI  - Optimized sample preparation for tandem capillary electrophoresis single-stranded
      conformational polymorphism/ heteroduplex analysis.
AB  - Here we describe DNA sample preparation methods that allow the rapid,
      simultaneous generation of both single-stranded conformational polymorphism
      (SSCP) and heteroduplex DNA elements from a single sample in a single tube, which
      are suitable for direct injection into a capillary electrophoresis (CE)
      instrument with excellent sensitivity of genetic mutation detection. The p53 gene
      was used as a model DNA region for this study, which was performed on a high
      throughput MegaBACE 96-capillary array electrophoresis instrument. We found that,
      contrary to the practice common in slab-gel SSCP analysis, denaturants such as
      formamide are incompatible with this novel technique because they result in homo-
      and heteroduplex peak broadening in CE (possibly as a result of incomplete dsDNA
      re-hybridization) that reduces the peak resolution and hence the sensitivity of
      mutation detection. We also have found that PCR buffers, which are typically used
      to suspend samples for slab-gel heteroduplex analysis (HA), but which are less
      suitable for CE because of the presence of extra salt that reduces the efficiency
      of electrokinetic injection, may be substituted with a 10 mM Tris-HCI buffer (pH
      8.5). The use of this Tris-HCl buffer for sample preparation provides both a high
      sensitivity of mutation detection by tandem SSCP/HA and high efficiency
      ofelectrokinetic injection by CE. In a related study (published elsewhere), we
      have applied this optimized protocol to the screening of a set of 32 mutant DNA
      samples from p53 exons 7 and 8 and recorded 100% sensitivity of mutation
      detection for tandem CE-SSCP/HA, whereas each individual method yielded lower
      sensitivity on its own (93% for SSCP and 75% for HA).

PMID- 12188185
TI  - Normalization of transfection efficiency using the beta-lactamase gene of the
      pGL3 luciferase vector in primary anterior pituitary cells.
AB  - The beta-galactosidase reporter gene is commonly used as a control for
      transfection efficiency in the promoter reporter assay system. While
      investigating vasoactive intestinal peptide response elements in the promoter of
      the prolactin gene, we found that primary pituitary cells from turkey hens highly
      expressed endogenous beta-galactosidase. Therefore, we developed a new protocol
      for determining transfection efficiency using the beta-lactamase gene, which is
      present on many expression vectors. Transcript levels of beta-lactamase were
      measured by RT-PCR after transfection of different amounts of the pGL3-basic and
      pGL3-control vectors. A high correlation was observed between the amount of
      plasmid transfected and beta-lactamase mRNA levels. Although no eukaryotic
      promoter was present, there was apparently leaky expression of the beta-lactamase
      gene. Expression of beta-lactamase was independent of expression from the simian
      virus 40 or turkey prolactin promoters cloned upstream of the luciferase gene.

PMID- 12188186
TI  - A decade of differential display.
AB  - It has been 10 years since the invention of differential display (DD), a
      conceptually simple methodology that allows the detection and identification of
      differentially expressed genes. In the past decade, the number of publications
      describing successful applications of DD has outnumbered those using any other
      competing methodologies, including subtractive hybridization, representational
      difference analysis, serial analysis of gene expression, and DNA microarrays.
      This review will provide a glimpse of the current progress made in DD
      technological development, refinement, and automation. Excellent examples of DD
      applications in studying a variety of biological problems, in such diverse
      biological systems as bacteria, yeast, flies, plants, and higher mammals, are
      presented to provide a roadmap for those who would like to pursue a fruitful gene
      "fishing" expedition. Some of the fundamental differences between DD and DNA
      microarrays are also discussed.

PMID- 12188187
TI  - Recovery of adherent cells after in situ electroporation monitored electrically.
AB  - Here we describe various experiments that address the efficiency of loading
      extracellular probes into the cytoplasm of adherent mammalian cells (normal rat
      kidney, Madin-Darby canine kidney, and African green monkey) by means of in situ
      electroporation. Subsequent cell recovery from the electroporation pulse was
      monitored electrically in real time for each condition. In this study, small,
      gold-film electrodes (5 x 10(-4) cm2) are used as culture substrates and at the
      same time as an electrode for both the application of the electroporating voltage
      pulse and the noninvasive electrical monitoring of cell recovery, using a
      technique referred to as ECIS. Electroporation has been performed by using ac
      sinusoidal voltage pulses of varying frequency, amplitude, and duration.
      Permeabilization and re-closure of the plasma membrane were evaluated by the
      uptake of the fluorescence probe, Lucifer Yellow, from the extracellularfluid.
      With the experimental setup described here, efficient electroporation was
      achieved with voltages less than 5 V. Using ECIS, we followed the morphological
      response of the cells to the electricfield-induced membrane permeabilization. For
      optimized electroporation conditions, cell recovery was completed in less than 1
      h. The introduction of membrane-impermeable substances by electroporation and in
      situ monitoring of the cellular response mayfind many applications in cell
      biology.

PMID- 12188188
TI  - Simultaneous, real-time imaging of intracellular calcium and cellular traction
      force production.
AB  - Cells can sense and respond to different types of mechanical stimuli that can
      lead to changes in rate of cell division, cell orientation, cell motility, and
      gene expression. There is rapidly growing interest in understanding how these
      processes are regulated by mechano-chemical signaling mechanisms. The movement
      offish epithelial keratocytes is regulated by the activation of stretch-activated
      calcium channels, which allow cells to trigger retraction of the rear cell
      margin, when forward movement is impeded. We have developed a new assay that
      permits imaging of intracellular calcium concentration simultaneously with the
      detection of traction forces generated by moving keratocytes. The assay consists
      of a thin sheet of gelatin embedded with a surface layer of small fluorescent
      marker beads, on which cells can move. The elastic properties of the gelatin
      substrata can be reproducibly varied over a wide range and are stable for long
      periods, while submerged beneath culture medium. Gelatin substrata are thin,
      transparent, and highly elastic, allowing real-time detection of changes in
      traction force production that are associated with transient increases in
      intracellular calcium and that occur in response to mechanical stretching.

PMID- 12188189
TI  - Customized microinjection glass capillary needles for P-element transformations
      in Drosophila melanogaster.
AB  - Here we describe how to generate customized microinjection needles from glass
      capillary tubes. Controls demonstrate the range of variables and effects on
      needle tip shape using a standard Flaming/Brown micropipet needle puller. Needles
      generated with two-cycle pulls provide a wider range of needle shapes in a
      predictable fashion. We used the needle puller's ramp function for multiple-cycle
      programs to determine the useful range of heat settings inherent to the glass
      capillary tube. This articlefocuses primarily on the preparation of injection
      needles utilized for P-element-mediated germ-line transformation in Drosophila
      melanogaster that do not require the dechorionation of the egg. However, these
      types of needles can be usefulfor numerous other types of injections, such as RNA
      interference, homologous recombination mutagenesis, morpholinos, transient gene
      regulation, drug delivery, and the transfer of cytoplasmic factors that are
      useful in a wide range of biological systems ranging from plants to vertebrates.
      Using our standard needle, we correlate the survival of injected D. melanogaster
      embryos with transformation efficiencies and plasmid construct characteristics.

PMID- 12188190
TI  - Application of cDNA arrays to monitor mRNA profiles in single preimplantation
      mouse embryos.
AB  - Array technology is a widely used tool for gene expression profiling in various
      biological systems. However, the application of this method to mammalian
      preimplantation embryos is limited by the small amount of mRNA that can be
      extracted from a single embryo, which is not sufficient for array analysis. Here
      we report a protocolfor the rapid global amplification of embryonic mRNA that
      permits the generation of expression profiles from single murine blastocysts. The
      approach combines global PCR and 77 RNA polymerase amplification and allows the
      preparation of labeled, amplified RNA for array hybridization from single murine
      blastocysts containing approximately 1.5 pg mRNA in less than 12 h. We
      demonstrate that this amplification procedure is highly reproducible and does not
      bias original relative mRNA levels. Signal patterns from various embryonic stages
      of murine development revealed marked differences in mRNA expression that were in
      accordance with previously published data. We found genes known to be involved in
      embryonic apoptosis expressed at different levels in individual murine day 3.5
      blastocysts. This technique can thus be used to assess embryonic viability and
      investigate molecular mechanisms of embryonic development.

PMID- 12188191
TI  - Denaturing HPLC for identifying bacteria.
AB  - Denaturing HPLC (DHPLC) is used in a wide variety of genetic applications. Here
      we introduce a new application for this technique, the identification of
      bacteria. We combined the capability of DHPLC to detect sequence variation with
      the principles of rRNA genotyping analysis to develop a high-throughput method of
      identifying microorganisms. Thirty-nine bacterial species from a broad spectrum
      of genera were tested to determine if DHPLC could be usedfor identification. Most
      (36 of 39) species of bacteria had a unique peak profile that could be used as a
      molecular fingerprint. Furthermore, a blind panel of 65 different bacterial
      isolates was analyzed to demonstrate the diagnostic capability of this method to
      specifically identify Yersinia pestis and Bacillus anthracis. All the Y. pestis
      samples (10 of 10) and the majority of B. anthracis samples (12 of 14) were
      correctly identified. The procedure had an overall specificity of 100%, overall
      sensitivity of 91.7%, and a predictive value of 96.9%. The data suggest that
      DHPLC of products spanning regions of genetic variability will be a useful
      application for bacterial identification.

PMID- 12188193
TI  - Real-time DNA quantification of nuclear and mitochondrial DNA in forensic
      analysis.
AB  - The rapid development of molecular genetic analysis tools has made it possible to
      analyze most biological materialfound at the scene of a crime. Evidence materials
      containing DNA quantities too low to be analyzed using nuclear markers can be
      analyzed using the highly abundant mtDNA. However, there is a shortage of
      sensitive nDNA and mtDNA quantification assays. In this study, an assay for the
      quantification of very small amounts of DNA, based on the real-time Taq-Man
      assay, has been developed. This analysis will provide an estimate of the total
      number of nDNA copies and the total number of mtDNA molecules in a particular
      evidence material. The quantification is easy to perform, fast, and requires a
      minimum of the valuable DNA extracted from the evidence materiaL The results will
      aid in the evaluation of whether the specific sample is suitable for nDNA or
      mtDNA analysis. Furthermore, the optimal amount of DNA to be used in further
      analysis can be estimated ensuring that the analysis is successful and that the
      DNA is retained for future independent analysis. This assay has significant
      advantages over existing techniques because of its high sensitivity, accuracy,
      and the combined analysis of nDNA and mtDNA. Moreover, it has the potential to
      provide additional information about the presence of inhibitors in forensic
      samples. Subsequent mitochondrial and nuclear analysis of quantified samples
      illustrated the potential to predict the number of DNA copies required for a
      successful analysis in a certain typing assay.

PMID- 12188192
TI  - Yeast "knockout-and-rescue" system for identification of eIF4E-family members
      possessing eIF4E-activity.
AB  - Evidence from several laboratories and sequencing projects has revealed that many
      eukaryotes contain multiple proteins related in sequence to the human mRNA-cap
      binding translation initiation factor 4E (eIF4E-1). Although some have been shown
      to bind cap-analogues, whether all eIF4E-family members function as translation
      initiation factors is unclear Furthermore, the existence of proteins related to
      eIF4E complicates the identification of the translation factor by sequence-based
      approaches. Methods to assess the functionality of eIF4E are limited. The most
      informative, single assay to identify proteins with eIF4E-activity is that of
      rescue of the lethal disruption of the single Saccharomyces cerevisiae eIF4E
      gene. We have developed a simplified yeast eIF4E "knockout-and-rescue" system,
      the characteristics of which are (i) a haploid system that obviates the needfor a
      "plasmid shuffle", (ii) a simple G418-based selection for yeast lacking a
      chromosomal eIF4E gene, and (iii) a glucose-based selection to deplete the strain
      of a human eIF4E-1 substitute and to assess the eIF4E-activity of an untested
      elF4E-family member In this form, the yeast eIF4E knockout-and-rescue system
      becomes a tool available to any laboratory experienced in the selection of
      microbial strains with antibiotics and standard media for the identification and
      isolation of cDNAs encoding proteins with eIF4E-activity.

PMID- 12188194
TI  - Streamlined approach to functional analysis of promoter-region polymorphisms.
AB  - We have developed a rapid method for identifying functional promoter-region
      polymorphisms. Using a modified pGL3 luciferase expression T-vector, we can
      amplify by PCR, clone, identify allelic pairs of a polymorphic gene promoter
      region, and prepare plasmids for cell culture 10 promoters (20 allele pairs) per
      week per researcher. By utilizing 96-well plate technology and an internal
      control plasmid expressing secreted alkaline phosphatase, each of these allele
      pairs can be tested for relative promoter activity in each of three cell lines
      (HEK293t, TE671, and JEG3) with similar resources.

PMID- 12188195
TI  - Multichannel plating unit for high-throughput plating of cell cultures.
AB  - High-throughput genomic approaches to gene function or target identification have
      led to the development and implementation of the 96-well format for many standard
      molecular biology manipulations. The apparatus described here, a Multichannel
      Plating Unit, is designed to plate out individual cultures efficientlyfrom
      standard 96-well culture blocks. Following transformation, aliquots of culture
      are loaded onto sterile beads that are rolled along individual channels of agar
      media. After the beads traverse the channel, they drop into the exit alley for
      disposal via an exit pore. The apparatus presented has 12 individual lanes, and
      the spacing is compatible with a standard 12-channel pipettor Thus, the unit
      allows for the rapid plating of 12 individual cultures at a time. For one 96-well
      block of transformants, this method reduces the labeling and plating effort from
      96 culture dishes that are spread individually to eight multichannel plates. The
      savings in time, materials, and storage space is significant

PMID- 12188197
TI  - Robust and sensitive nylon hybridization membrane suitable for high-throughput
      robotic arraying applications.
AB  - An important aspect of automated macroarraying is the suitability of the nylon
      membrane selected on which samples are to be arrayed. PerForma is a positively
      charged nylon membrane that has been developed specificallyfor automated
      macroarraying. Tests usingfluorescent hybridization detection methods have shown
      that immobilized DNA amounts as low as 0.25 pg can be detected and that positive
      signals are obtainable after 21 stripping cycles. This report describes the
      improved colony growth, improved handling characteristics, increased
      hybridization detection sensitivity, and increased stripping and reprobing
      capability obtained using PerForma.

PMID- 12188196
TI  - Nonradioactive detection of retroviral-associated RNase H activity in a
      microplate-based, high-throughput format.
AB  - None of the available antiretroviral drugs that are currently used in the clinic
      to treat infection with HIV-1 is directed against the RNase H active site of the
      reverse transcriptase. Here we developed a nonradioactive, 96-well plate assay
      designed to be used for high-throughput screening of compounds capable of
      inhibiting the RNase H activity of HIV-1 reverse transcriptase. We employed a
      tRNA as substrate that was labeled with digoxygenin-modified reporter residues.
      The labeled tRNA was prehybridized with a DNA oligonucleotide that contained a
      single biotinylated residue at its 5'-terminus to ensure its attachment to
      streptavidin-coated microplates. The uncleaved, immobilized DNA/tRNA substrate
      was detected through the use of established ELISA protocols. Incubation with
      purified HIV-1 reverse transcriptase initiated RNase H degradation and caused a
      signal reduction to negligible background levels. In contrast, the signal
      intensity remained unaffected when using an RNase H deficient mutant enzyme. The
      assay was validated using the hydrazone derivative BBNH that was previously shown
      to inhibit RNase H degradation below concentrations of 10 microM.

PMID- 12188198
TI  - Compact disc with both numeric and genomic information as DNA microarray
      platform.
AB  - The compact disc (CD) is an ideal toolfor reading, writing, and storing numeric
      information. It was used in this work as a support for constructing DNA
      microarrays suited for genomic analysis. The CD was divided into two functional
      areas: the external ring of the CD was used for multiparametric DNA analysis on
      arrays, and the inner portion was usedfor storing numeric information. Because
      polycarbonate and CD resins autofluoresce, a colorimetric method for DNA
      microarray detection was used that is well adaptedfor the fast detection
      necessary when using a CD reader. A double-sided CD reader was developed for the
      simultaneous analysis of both array and numeric data. The numeric data are
      engraved as pits in the CD tracks and result in the succession of 0/1, which
      results from the modulation of the laser reflection when one reads the edges of
      the pits. Another diffraction-based laser was placed above the CD for the
      detection of the DNA targets on the microarrays. Both readersfit easily in a PC
      tower. Both numeric and genomic information data were simultaneously acquired,
      and each array was reconstituted, analyzed, and processed for quantification by
      the appropriate software.

PMID- 12188200
TI  - Self-sealing, large bore arterial punctures: a counterintuitive new phenomenon.
AB  - The human femoral artery can bleed dangerously following the removal of a
      catheter uring cardiac catheterization. In this study, a modified technique of
      needle insertion, simply inserting the needle bevel-down instead of the standard
      bevel-up approach, was tested as a means to reduce bleeding after catheter
      removal. Large bore needle punctures were made in surgically exposed arteries of
      anesthetized pigs using either a standard technique (45 degree approach, bevel
      up) or a modified technique (25 degree approach, bevel down). For half the
      punctures, topical phenylephrine solution (1 mg/ml) was applied to the adventitia
      of the artery to cause constriction. Median bleeding rates were reduced from 81
      to less than 1 ml/min/100 mmHg intraluminal pressure by the modified technique
      with application of phenylephrine. In most cases zero bleeding, that is self
      sealing, of the arteries occurred. It is postulated that a flap-valve of tissue
      created by the modified technique produced this self-sealing behavior.
      Sophisticated modeling studies are needed to fully understand this new
      phenomenon.

PMID- 12188199
TI  - Mucosal folding in biologic vessels.
AB  - A two-layer model is used to simulate the mechanical behavior of an airway or
      other biological vessel under external compressive stress or smooth muscle
      constriction sufficient to cause longitudinal mucosal buckling. Analytic
      andfinite element numerical methods are used to examine the onset of buckling.
      Post-buckling solutions are obtained by finite element analysis, then verified
      with large-scale physical model experiments. The two-layer model provides insight
      into how the stiffness of a vessel wall changes due to changes in the geometry
      and intrinsic material stiffnesses of the wall components. Specifically, it
      predicts that the number of mucosal folds in the buckled state is diminished most
      by increased thickness of the inner collagen-rich layer, and relatively little by
      increased thickness of the outer submucosal layer. An increase in the ratio of
      the inner to outer material stiffnesses causes an intermediate reduction in the
      number of folds. Results are cast in a simple form that can easily be used to
      predict buckling in a variety of vessels. The model quantitatively confirms that
      an increase in the thickness of the inner layer leads to a reduction in the
      number of mucosal folds, and further, that this can lead to increased vessel
      collapse at high levels of smooth muscle constriction.

PMID- 12188201
TI  - A new method for predicting the opening angle for soft tissues.
AB  - The purpose of this paper is to present a simple new method for calculating the
      opening angle produced by a given residual stress field in a soft biological
      tissue. The method uses minimization of potential energy, and is therefore named
      the MPE method. The accuracy of the MPE method is evaluated by comparing the
      opening angle it predicts to results from a finite element model of the opening
      angle experiment. We show that the MPE method provides good predictions of the
      opening angle, and that it is significantly more accurate than two other methods
      previously used in the literature.

PMID- 12188202
TI  - A three-dimensional finite element model for arterial clamping.
AB  - Clamp induced injuries of the arterial wall may determine the outcome of surgical
      procedures. Thus, it is important to investigate the underlying mechanical
      effects. We present a three-dimensional finite element model, which allows the
      study of the mechanical response of an artery-treated as a two-layer tube-during
      arterial clamping. The important residual stresses, which are associated with the
      load-free configuration of the artery, are also considered. In particular, the
      finite element analysis of the deformation process of a clamped artery and the
      associated stress distribution is presented. Within the clamping area a zone of
      axial tensile peak-stresses was identified, which (may) cause intimal and medial
      injury. This is an additional injury mechanism, which clearly differs from the
      commonly assumed wall damage occurring due to compression between the jaws of the
      clamp. The proposed numerical model provides essential insights into the
      mechanics of the clamping procedure and the associated injury mechanisms. It
      allows detailed parameter studies on a virtual clamped artery, which can not be
      performed with other methodologies. This approach has the potential to identify
      the most appropriate clamps for certain types of arteries and to guide optimal
      clamp design.

PMID- 12188203
TI  - Influence of connection geometry and SVC-IVC flow rate ratio on flow structures
      within the total cavopulmonary connection: a numerical study.
AB  - The total cavopulmonary connection (TCPC) is a palliative cardiothoracic surgical
      procedure used in patients with one functioning ventricle that excludes the heart
      from the systemic venous to pulmonary artery pathway. Blood in the superior and
      inferior vena cavae (SVC, IVC) is diverted directly to the pulmonary arteries.
      Since only one ventricle is left in the circulation, minimizing pressure drop by
      optimizing connection geometry becomes crucial. Although there have been
      numerical and in-vitro studies documenting the effect of connection geometry on
      overall pressure drop, there is little published data examining the effect of SVC
      IVC flow rate ratio on detailed fluid mechanical structures within the various
      connection geometries. We present here results from a numerical study of the TCPC
      connection, configured with various connections and SVC:IVC flow ratios. The role
      of major flow parameters: shear stress, secondary flow, recirculation regions,
      flow stagnation regions, and flow separation, was examined. Results show a
      complex interplay among connection geometry, flow rate ratio and the types and
      effects of the various flow parameters described above. Significant changes in
      flow structures affected local distribution of pressure, which in turn changed
      overall pressure drop. Likewise, changes in local flow structure also produced
      changes in maximum shear stress values; this may have consequences for platelet
      activation and thrombus formation in the clinical situation. This study sheds
      light on the local flow structures created by the various connections andflow
      configurations and as such, provides an additional step toward understanding the
      detailed fluid mechanical behavior of the more complex physiological
      configurations seen clinically.

PMID- 12188204
TI  - Unsteady and three-dimensional simulation of blood flow in the human aortic arch.
AB  - A three-dimensional and pulsatile blood flow in a human aortic arch and its three
      major branches has been studied numerically for a peak Reynolds number of 2500
      and a frequency (or Womersley) parameter of 10. The simulation geometry was
      derived from the three-dimensional reconstruction of a series of two-dimensional
      slices obtained in vivo using CAT scan imaging on a human aorta. The numerical
      simulations were obtained using a projection method, and a finite-volume
      formulation of the Navier-Stokes equations was used on a system of overset grids.
      Our results demonstrate that the primary flow velocity is skewed towards the
      inner aortic wall in the ascending aorta, but this skewness shifts to the outer
      wall in the descending thoracic aorta. Within the arch branches, the flow
      velocities were skewed to the distal walls with flow reversal along the proximal
      walls. Extensive secondary flow motion was observed in the aorta, and the
      structure of these secondary flows was influenced considerably by the presence of
      the branches. Within the aorta, wall shear stresses were highly dynamic, but were
      generally high along the outer wall in the vicinity of the branches and low along
      the inner wall, particularly in the descending thoracic aorta. Within the
      branches, the shear stresses were considerably higher along the distal walls than
      along the proximal walls. Wall pressure was low along the inner aortic wall and
      high around the branches and along the outer wall in the ascending thoracic
      aorta. Comparison of our numerical results with the localization of early
      atherosclerotic lesions broadly suggests preferential development of these
      lesions in regions of extrema (either maxima or minima) in wall shear stress and
      pressure.

PMID- 12188205
TI  - A modified micropipette aspiration technique and its application to tether
      formation from human neutrophils.
AB  - Tether formation, which is mechanically characterized by its threshold force and
      effective viscosity, is involved in neutrophil emigration from blood circulation.
      Using the micropipette aspiration technique, which was improved by quantitative
      contact control and computerized data analysis, we extracted tethers from human
      neutrophils treated with IL-8, PMA, or cytochalasin D. We found that both IL-8
      and PMA elevated the threshold force to about twice as large as the value for
      passive neutrophils. All these treatments decreased the effective viscosity
      dramatically (approximately 80%). With a novel method, the residual cortical
      tension of the cytochalasin-D-treated non-spherical neutrophils was measured to
      be approximately 8.8 pN/microm.

PMID- 12188206
TI  - A new in vitro model to evaluate differential responses of endothelial cells to
      simulated arterial shear stress waveforms.
AB  - In the circulation, flow-responsive endothelial cells (ECs) lining the lumen of
      blood vessels are continuously exposed to complex hemodynamic forces. To increase
      our understanding of EC response to these dynamic shearing forces, a novel in
      vitro flow model was developed to simulate pulsatile shear stress waveforms
      encountered by the endothelium in the arterial circulation. A modified waveform
      modeled after flow patterns in the human abdominal aorta was used to evaluate the
      biological responsiveness of human umbilical vein ECs to this new type of
      stimulus. Arterial pulsatile flow for 24 hours was compared to an equivalent time
      average steady laminar shear stress, using no flow (static) culture conditions as
      a baseline. While both flow stimuli induced comparable changes in cell shape and
      alignment, distinct patterns of responses were observed in the distribution of
      actin stress fibers and vinculin-associated adhesion complexes, intrinsic
      migratory characteristics, and the expression of eNOS mRNA and protein. These
      results thus reveal a unique responsiveness of ECs to an arterial waveform and
      begin to elucidate the complex sensing capabilities of the endothelium to the
      dynamic characteristics of flows throughout the human vascular tree.

PMID- 12188207
TI  - Assessment of mechanical properties of adherent living cells by bead
      micromanipulation: comparison of magnetic twisting cytometry vs optical tweezers.
AB  - We compare the measurements of viscoelastic properties of adherent alveolar
      epithelial cells by two micromanipulation techniques: (i) magnetic twisting
      cytometry and (ii) optical tweezers, using microbeads of same size and similarly
      attached to F-actin. The values of equivalent Young modulus E, derived from
      linear viscoelasticity theory, become consistent when the degree of bead
      immersion in the cell is taken into account. E-values are smaller in (i) than in
      (ii): approximately 34-58 Pa vs approximately 29-258 Pa, probably because higher
      stress in (i) reinforces nonlinearity and cellular plasticity. Otherwise, similar
      relaxation time constants, around 2 s, suggest similar dissipative mechanisms.

PMID- 12188208
TI  - Influence of the lateral ventricles and irregular skull base on brain kinematics
      due to sagittal plane head rotation.
AB  - Two-dimensional physical models of the human head were used to investigate how
      the lateral ventricles and irregular skull base influence kinematics in the
      medial brain during sagittal angular head dynamics. Silicone gel simulated the
      brain and was separatedfrom the surrounding skull vessel by paraffin that
      provided a slip interface between the gel and vessel. A humanlike skull base
      model (HSB) included a surrogate skull base mimicking the irregular geometry of
      the human. An HSBV model added an elliptical inclusion filled with liquid
      paraffin simulating the lateral ventricles to the HSB model. A simplified skull
      base model (SSBV) included ventricle substitute but approximated the anterior and
      middle cranial fossae by a flat and slightly angled surface. The models were
      exposed to 7600 rad/s2 peak angular acceleration with 6 ms pulse duration and 5
      deg forced rotation. After 90 deg free rotation, the models were decelerated
      during 30 ms. Rigid body displacement, shear strain and principal strains were
      determined from high-speed video recorded trajectories of grid markers in the
      surrogate brains. Peak values of inferior brain surface displacement and strains
      were up to 10.9X (times) and 3.3X higher in SSBV than in HSBV. Peak strain was up
      to 2.7X higher in HSB than in HSBV. The results indicate that the irregular skull
      base protects nerves and vessels passing through the cranial floor by reducing
      brain displacement and that the intraventricular cerebrospinal fluid relieves
      strain in regions inferior and superior to the ventricles. The ventricles and
      irregular skull base are necessary in modeling head impact and understanding
      brain injury mechanisms.

PMID- 12188209
TI  - Origin of the biomechanical properties of wood related to the fine structure of
      the multi-layered cell wall.
AB  - In this study, a basic model is introduced to describe the biomechanical
      properties of the wood from the viewpoint of the composite structure of its cell
      wall. First, the mechanical interaction between the cellulose microfibril (CMF)
      as a bundle framework and the lignin-hemicellulose as a matrix (MT) skeleton in
      the secondary wall is formulated based on "the two phase approximation."
      Thereafter, the origins of (1) tree growth stress, (2) shrinkage or swelling
      anisotropy of the wood, and (3) moisture dependency of the Young's modulus of
      wood along the grain were simulated using the newly introduced model. Through the
      model formulation; (1) the behavior of the cellulose microfibril (CMF) and the
      matrix substance (MT) during cell wall maturation was estimated; (2) the moisture
      reactivity of each cell wall constituent was investigated; and (3) a realistic
      model of the fine composite structure of the matured cell wall was proposed.
      Thus, it is expected that the fine structure and internal property of each cell
      wall constituent can be estimated through the analyses of the macroscopic
      behaviors of wood based on the two phase approximation.

PMID- 12188210
TI  - Competing effects of buckling and anchorage strength on optimal wheat stalk
      geometry.
AB  - We seek the ideal wheat stalk, which minimizes the structural mass required to
      support a fixed grain load in the presence of gravity and wind. The optimization
      search is restricted to stepped cylindrical stems of known moduli and density but
      unknown dimension. Stem buckling and root anchorage strength are assumed to place
      restrictions on the permissible stalk resonant frequency in the presence of a
      specified wind forcing frequency. These effects are described mathematically, and
      the penalty parameter method is used to find stem mass minima for various stalk
      heights. In general, there are two alternative solution branches. The lower
      solution is the global minimum but it is probably impractical for field crops
      exposed to natural wind. The upper minimum is more conservative and therefore
      requires more stem mass. Due to the competing requirements of buckling versus
      anchorage strength, the parameter study shows that optimal wheat stem geometry
      has a nonlinear dependence on the intensity of gravity and the frequency spectra
      of the wind.

PMID- 12188211
TI  - MRI gradient coil cylinder sound field simulation and measurement.
AB  - High-field, high-speed Magnetic Resonance Imaging (MRI) generates high sound
      levels within and nearby the scanner. The mechanism and process that produces the
      gradient magnetic field (a cylindrical electro-magnet, called the gradient coil
      cylinder, which produces a spatially and temporally varying magnetic field inside
      a static background magnetic field) is the primary source of this noise. This
      noise can cause difficulties in verbal communication in and around the scanner,
      heightened patient anxiety, temporary hearing loss and possible permanent hearing
      impairment for health care workers and patients. In order to effectively suppress
      the sound radiation from the gradient coil cylinder the sound field within and
      nearby the gradient coil needs to be characterized This characterization may be
      made using an analytical solution of the sound pressure field, computational
      simulation, measurement analysis or some combination of these three methods. This
      paper presents the computational simulation and measurement results of a study of
      the sound radiation from a head and neck gradient coil cylinder within a 4 Tesla
      MRI whole body scanner. The measurement results for the sound pressure level
      distribution along the centerline of the gradient coil cylinder are presented.
      The sound pressure distributions predicted from Finite Element Analysis of the
      gradient coil movement during operation and subsequent Boundary Element Analysis
      of the sound field generated are also presented. A comparison of the measured
      results and the predicted results shows close agreement. Because of the extremely
      complex nature of the analytical solution for the gradient coil cylinder, a
      treatment of the analytical solution and comparison to the computational results
      for a simple cylinder vibrating in a purely radial direction are also presented
      and also show close agreement between the two methods thus validating the
      computational approach used with the more complex gradient coil cylinder.

PMID- 12188212
TI  - Time-dependent circumferential deformation of cortical bone upon internal radial
      loading.
AB  - Short and long duration tests were conducted on hollow femoral bone cylinders to
      study the circumferential (hoop) creep response of cortical bone subjected to an
      intramedullary radial load. It was hypothesized that there is a stress threshold
      above which nonlinear creep effects dominate the mechanical response and below
      which the response is primarily determined by linear viscoelastic material
      properties. The results indicate that a hoop stress threshold exists for cortical
      bone, where creep strain, creep strain rate and residual strain exhibited linear
      behavior at low hoop stress and nonlinear behavior above the hoop stress
      threshold. A power-law relationship was used to describe creep strain as a
      function of hoop stress and time and damage morphology was assessed.

PMID- 12188213
TI  - Predicting the failure response of cement-bone constructs using a non-linear
      fracture mechanics approach.
AB  - A non-linear fracture mechanics approach was used to predict the failure response
      of complex cement-bone constructs. A series of eight mechanical tests with a
      combination of tensile and shear loading along the cement-bone interface was
      performed. Each experiment was modeled using the finite element method with non
      linear constitutive models at the cement-bone interface. Interface constitutive
      parameters were assigned based on the quantity of bone interdigitated with the
      cement. There was a strong correlation (r2 = 0.80) between experimentally
      measured and finite element predicted ultimate loads. The average error in
      predicted ultimate load was 23.9 percent. In comparison to the ultimate load
      predictions, correlations and errors for total energy to failure (r2 = 0.24, avg.
      error = 38.2 percent) and displacement at 50 percent of the ultimate load (r2 =
      0.27, avg. error = 52.2 percent) were poor The results indicate that the non
      linear constitutive laws could be useful in predicting the initiation and
      progression of interface failure of cemented bone-implant systems. However
      improvements in the estimation of post-yield interface properties from the
      quantity of bone interdigitated with cement are needed to enhance predictions of
      the overall failure response.

PMID- 12188214
TI  - Multi-axial spine biomechanical testing system with speckle displacement
      instrumentation.
AB  - This paper reports on the design and development of a multi-axis (up to 6 axes)
      mechanical tester for spinal research and testing. The developed spine tester
      allowed true motion to be simulated on a specimen in pure or combined modes. To
      demonstrate the capability of the new tester flexural stiffness properties of
      sheep lumbar motion segments were evaluated together wiith a non-contact speckle
      displacement measurement system. The flexural stiffness of the specimens was
      measured and compared under constrained and non-constrained testing conditions;
      with relieving of shear forces (non-constrained), it was found that the specimen
      behaved in a 'stiffer' manner.

PMID- 12188215
TI  - Trypanosome alternative oxidase is regulated post-transcriptionally at the level
      of RNA stability.
AB  - In the bloodstream form of African trypanosomes, trypanosome alternative oxidase
      (TAO), the non-cytochrome ubiquinol:oxidoreductase, is the only terminal oxidase
      of the mitochondrial electron transport system. TAO is developmentally regulated
      during mitochondrial biogenesis in this parasite. During in vitro differentiation
      of Trypanosoma brucei from the bloodstream to the procyclic form, the overall
      rate of oxygen consumption decreased about 80%. The mode of respiration changed
      over a 2- to 3-wk period from a cyanide-insensitive, SHAM-sensitive pathway to a
      predominantly cyanide-sensitive pathway. The TAO protein level gradually
      decreased to the level present in the procyclic forms during this 3-wk period.
      However, within the first week of differentiation, the TAO transcript level
      decreased about 90% and then in the following weeks it reached the level present
      in the established procyclic form, that is about 20% of that in bloodstream
      forms. Like other trypanosomatid genes TAO transcript synthesis remains unaltered
      in fully differentiated bloodstream and procyclic trypanosomes. The half-life of
      the TAO mRNA was about 3.2 h in the procyclic trypanosomes, whereas the TAO
      transcript level remained unaltered even after 4 h of incubation with actinomycin
      D in bloodstream forms. Inhibition of protein synthesis resulted in about a four
      fold accumulation of the TAO transcript in the procyclic trypanosomes, comparable
      to the level present in the bloodstream forms. Thus, TAO is regulated at the
      level of mRNA stability and de novo protein synthesis is required for the
      reduction of the TAO mRNA pool in the procyclic form.

PMID- 12188216
TI  - Infectivity and virulence of Leishmania donovani promastigotes: a role for media,
      source, and strain of parasite.
AB  - Transformation of promastigotes of Leishmania donovani strain AG83 from
      amastigotes derived from an infected animal was studied in three media,
      Schneider's Drosophila medium (SDM), Medium 199 (M199), and biphasic M199 (B
      M199) with 10% fetal bovine serum. The media, SDM and B-M199, both supported a
      more efficient transformation of promastigotes in comparison with M199.
      Infectivity studies in hamsters and BALB/c mice showed that promastigotes
      isolated in B-M199 were several folds more infective than those obtained from
      M199. Comparison of the infectivity and virulence of promastigotes of AG83, with
      a recent isolate of kala-azar, SL94, harvested under similar conditions, revealed
      greater infectivity of SL94 for both macrophages and animal models. The present
      study demonstrates that the medium used for the conversion of amastigotes to
      promastigotes plays a major role in determining the infectivity of the freshly
      transformed L. donovani promastigotes in hamsters and BALB/c mice. The source and
      the strain of the parasite also influence the outcome of L. donovani infection.

PMID- 12188217
TI  - A PCR-based survey on Phytomonas (Euglenozoa: Trypanosomatidae) in phytophagous
      hemipterans of the Amazon region.
AB  - We have surveyed 244 hemipterans from Western Brazilian Amazjnia for the presence
      of trypanosomatids and identification of members of the genus Phytomonas.
      Examination by phase microscopy of squashes of insect salivary glands (SG) and
      digestive tubes (DT) revealed that 44% (108/244) of insects from seven families
      harbored trypanosomatids. Infections were 5 times more frequent in Coreidae than
      in all other families together. Smears of SG and DT of the dissected insects were
      fixed on glass slides with methanol and stained with Giemsa for morphological
      analysis. DNA was recovered from these preparations and submitted to a PCR assay
      that permitted amplification of all trypanosomatid genera using primers of
      conserved sequences flanking a segment of the spliced leader (SL) gene. Upon PCR
      amplification of the recovered DNA, amplicons were hybridized with an
      oligonucletide probe (SL3') complementary to a SL intron sequence specific for
      flagellates of the genus Phytomonas. Among the trypanosomatid-positive insects,
      38.8% harbored Phytomonas spp., corresponding to an overall Phytomonas prevalence
      of 17.1% among phytophagous bugs, their putative vectors. Since many Phytomonas
      are pathogenic in plants, this high prevalence in their vectors emphasizes the
      permanent risk of exposure to disease by native and cultured plants of the Amazon
      region.

PMID- 12188218
TI  - Ecology, development and pathogenicity of Buddenbrockia plumatellae Schroder,
      1910 (Myxozoa, Malacosporea) (syn. Tetracapsula bryozoides) and establishment of
      Tetracapsuloides n. gen. for Tetracapsula bryosalmonae.
AB  - Buddenbrockia plumatellae, an enigmatic worm-like myxozoan, was observed as
      continuously writhing free and attached 'worms' and as free mature spores in the
      coelom of the freshwater bryozoans Plumatella fungosa, Hyalinella punctata, and
      Fredericella sp. 'Worm' numbers could double every three days. 'Worms' and spores
      could be expelled from colonies by external pressure. Some mature 'worms' exited
      actively, entraining release of free spores, and gradually ceased movement
      outside the host. Bryozoans sealed off infected regions of the colony. Infected
      colonies grew slowly, produced no statoblasts, and eventually regressed and died.
      Transmission was not achieved and prevalence was low. Electron microscopy of
      'worms' revealed a single layer of mural cells on a fibrous basal lamina
      overlying four longitudinal muscle blocks and an inner sheet of two types of
      proliferating cells, an organization indicative of the bilaterian ancestry of the
      Myxozoa. Primary type A cells were attached directly by striated tubules to mural
      cells at positions between muscle blocks. Secondary type A cells had a secretory
      function. Type B cells underwent meiosis and subsequently developed to typical
      malacosporean myxozoan spores filling the internal cavity of the 'worms'.
      External tubes were formed during capsulogenesis in 'worms' from Fredericella sp.
      Tetracapsula bryozoides is synonymised with Buddenbrockia plumatellae and a new
      genus is proposed for Tetracapsula bryosalmonae.

PMID- 12188219
TI  - Electrokaryotypes of macronuclei of several Paramecium species.
AB  - A comparative study of macronuclear DNA molecules from the following Paramecium
      species: the P. aurelia complex, P. caudatum, P. bursaria, P. putrinum and P.
      multimicronucleatum was performed using pulsed-field gel electrophoresis. The
      electrophoretic pattern was constant and unique for each species, and is referred
      to herein as its electrokaryotype. Large differences were observed between
      Paramecium species according to the range and major size of macronuclear DNA
      fragments, while different strains of the same species, even belonging to
      different syngens, were characterized by the same electrokaryotype. In this
      respect sibling species from the P. aurelia complex are as similar as syngens in
      other Paramecium species, but are unlike conventional species. The principles and
      value of electrokaryotype analysis for application to ciliates are discussed.

PMID- 12188220
TI  - Two forms of membrane-bound sphingosine kinase in Tetrahymena and activity
      changes during growth and the cell cycle.
AB  - Sphingosine kinase is responsible for the formation of sphingosine-1-phosphate, a
      sphingolipid mediator with important roles in numerous physiological processes.
      The sphingosine kinase activity of Tetrahymena pyriformis was recovered
      predominantly in the particulate fraction and it could be solubilised in 1% beta
      octylglucoside. Anion-exchange chromatography resolved the beta-octylglucoside
      solubilised sphingosine kinase activity into two peaks corresponding to proteins
      of Mr 140,000 and 80,000 respectively, as determined by subsequent size exclusion
      chromatography on Superdex 200. N,N-dimethylsphingosine did not inhibit the
      sphingosine kinase activity in either fraction, whereas D,L-threo
      dihydrosphingosine inhibited sphingosine phosphorylation by the Mr 80,000 kinase
      but had no effect on the Mr 140,000 kinase activity. The activities also showed
      different stimulatory responses to Triton X-100 or NaCl. Overall, the results
      suggest the existence in Tetrahymena of two distinct membrane-associated
      sphingosine kinases. The kinase activity determined at the different culture
      stages showed a transient elevation at the mid-logarithmic phase. Further, the
      sphingosine kinase activity was examined during the synchronous cell division
      induced by cyclic heat treatments in T. pyriformis. We report for the first time
      that the sphingosine kinase activity greatly increased at 30 to 45 min after the
      end of heat treatment prior to the synchronous cell division (75 min), suggesting
      that the activity changes were associated with the cell cycle and that the up
      regulated sphingosine kinase activity would be required for the initiation of the
      oncoming synchronous cell division in Tetrahymena cells.

PMID- 12188221
TI  - Direct visualization of the microtubular cytoskeleton of ciliated protozoa with a
      fluorescent taxoid.
AB  - Visualization of the infraciliature, which is an essential tool for the
      identification of ciliate species, has traditionally been obtained with silver
      proteinate methods. Since infraciliature is mainly composed of microtubules, we
      used the synthetic fluorescent taxoid FLUTAX as a method for ciliate
      identification. The main advantages of this method are the facility and rapidity
      of its application and the fact that no previous fixation and permeabilization
      processes are required. FLUTAX may also be used as a probe to follow
      morphogenetical changes in the microtubular cytoskeleton during the ciliate life
      cycle.

PMID- 12188222
TI  - In vitro leishmanicidal activity of a monoclonal antibody mimicking a yeast
      killer toxin.
AB  - The microbicidal effect of a monoclonal antiidiotypic antibody, mimicking the
      activity of a yeast killer toxin, characterized by a wide antimicrobial spectrum,
      has been evaluated in vitro against two relevant species of protozoan parasites,
      Leishmania major and Leishmania infantum. The antiidiotypic antibody exerted a
      significant and dose-dependent antileishmanial activity against parasite
      promastigotes in comparison to an irrelevant isotype-matched monoclonal antibody.
      This is the first demonstration that an antibody, which had been already shown to
      be fungicidal and bactericidal, may also exert a direct microbicidal activity
      against protozoa.

PMID- 12188223
TI  - Tolerance of soil flagellates to increased NaCl levels.
AB  - The ability of heterotrophic flagellates to survive and adapt to increasing
      salinities was investigated in this study. Whole soil samples were subjected to
      salinities corresponding to marine conditions and clonal cultures were used to
      perform growth and adaptation experiments at a wide range of different salinities
      (0-50 ppm). More morphotypes tolerant to elevated NaCl levels were found in road
      verge soil that was heavily exposed to de-icing salt than in less exposed soils,
      though there were fewer tolerant than intolerant morphotypes in all soils
      examined. Heterotrophic flagellates isolated on a freshwater medium from a non
      exposed soil were unable to thrive at salinities above 15 ppt, and showed reduced
      growth rates even at low salt salinities (1-5 ppt). The findings suggest that
      heterotrophic soil flagellates are less tolerant to NaCl than their aquatic
      relatives, possibly due to their long evolutionary history in soil, and support
      the idea that identical morphospecies may differ considerably with respect to
      physiology

PMID- 12188224
TI  - Redescription of Strombidium oculatum Gruber 1884 (Ciliophora, Oligotrichia).
AB  - The marine, tide pool-dwelling ciliate Stombidium oculatum was redescribed using
      live, stained, SEM, and TEM material prepared from samples collected from pools
      on the Isle of Man (Irish Sea) and Brittany (France). Also, we reviewed the older
      German and French works that reported on ciliates collected in the Mediterranean
      and Brittany, respectively. The Brittany and Isle of Man populations of the
      ciliate were considered identical. Some morphological and behavioural differences
      exist between the Brittany-Isle of Man populations and the Mediterranean
      populations, but they were insufficient to distinguish different taxa. Thus, taxa
      from all three locations were considered to be conspecific. Key features used to
      describe the ciliate were: morphology and ultrastructure of the free-swimming
      ciliate; cyst morphology; presence of mixotrophic-chloroplasts; presence of an
      eye spot composed of stigma obtained from chlorophyte prey; division,
      morphogenesis, and nuclear structure; live observations and behaviour, including
      the encystment-excystment cycle. Based on morphological and behavioural
      characteristics the taxon was distinguished from other similar species, and a
      neotype has been designated as no type material exists.

PMID- 12188225
TI  - A new species in the genus Cyrtostrombidium (Ciliophora, Oligotrichia,
      Oligotrichida): its morphology, seasonal cycle and resting stage.
AB  - Cysts of an oligotrich ciliate were collected from natural sediment samples in
      Onagawa Bay, northeastern coast of Japan, and examined for their excystment
      capability. A high excystment ratio was obtained at lower temperatures of 10 or
      15 degrees C; no excystment occurred at 20 degrees C. Excysted vegetative cells
      were observed after protargol staining and were identified as a new species,
      Cyrtostrombidium boreale n. sp. The seasonal changes in the vegetative population
      and sedimentation of newly formed cysts were also investigated in situ.
      Planktonic vegetative cells were abundant during the cold season from February to
      May, when the water temperature was lower than 10 degrees C. Mass encystment
      occurred abruptly just after the seasonal peak of the vegetative population in
      April. These results indicate that C. boreale is a cold-water species and
      aestivates during the longer, warm period from late spring to fall.

PMID- 12188226
TI  - Isolation of purified oocyst walls and sporocysts from Toxoplasma gondii.
AB  - Toxoplasma gondii oocysts are environmentally resistant and can infect virtually
      all warm-blooded hosts, including humans and livestock. Little is known about the
      biochemical basis for this resistance of oocysts, and mechanism for excystation
      of T. gondii sporozoites. The objective of the present study was to evaluate
      different methods (mechanical fragmentation, gradients, flow cytometry) to
      separate and purify T. gondii oocyst walls and sporocysts. Oocyst walls were
      successfully separated and purified using iodixanol gradients. Sporocysts were
      successfully separated and purified using iodixanol and Percoll gradients.
      Purification was also achieved by flow cytometry. Flow cytometry with
      fluorescence-activated cell sorting (FACS) yielded analytical quantities of
      oocyst walls and intact sporocysts. Flow cytometry with FACS also proved useful
      for quantitation of purity obtained following iodixanol gradient fractionation.
      Methods reported in this paper will be useful for analytical purposes, such as
      proteomic analysis of components unique to this life cycle stage, development of
      detection methods, or excystation studies.

PMID- 12188227
TI  - Life cycle, ultrastructure and molecular phylogeny of Hyalinocysta chapmani
      (Microsporidia: Thelohaniidae), a parasite of Culiseta melanura (Diptera:
      Culicidae) and Orthocyclops modestus (Copepoda: Cyclopidae).
AB  - The complete life cycle of the microsporidium Hyalinocysta chapmani is described
      from the primary mosquito host Culiseta melanura and the intermediate copepod
      host Orthocyclops modestus. Infections are initiated in larval C. melanura
      following the oral ingestion of uninucleate spores from infected copepods. Spores
      germinate within the lumen of the midgut and directly invade fat body tissue
      where all development occurs. Uninucleated schizonts undergo binary division
      (schizogony) followed by karyokinesis (nuclear division) to form diplokaryotic
      meronts. Merogony is by synchronous binary division. The onset of sporogony is
      characterized by the simultaneous secretion of a sporophorous vesicle and meiotic
      division of the diplokaryon resulting in the formation of eight ovoid meiospores
      enclosed within a sporophorous vesicle. Most infected larvae die during the
      fourth stadium and there is no evidence of a developmental sequence leading to
      vertical transmission. Hyalinocysta chapmani is horizontally transmitted to O.
      modestus via oral ingestion of meiospores. Infections become established within
      ovarian tissue of females and all parasite development is haplophasic.
      Uninucleate schizonts divide by binary division during an initial schizogonic
      cycle. Newly formed uninucleate cells produce a thin sporophorous vesicle and
      undergo repeated nuclear division during sporogony to produce a rosette-shaped,
      multinucleated sporogonial plasmodium with up to 18 nuclei. This is followed by
      cytoplasmic cleavage, sporogenesis, and disintegration of the sporophorous
      vesicle to form membrane-free uninucleate spores. Infected females eventually die
      and there is no egg development. The small subunit rDNA sequence of H. chapmani
      isolated from meiospores from C. melanura was identical to the small subunit rDNA
      sequence obtained from spores from O. modestus, corroborating the laboratory
      transmission studies and confirming the intermediary role of O. modestus in the
      life cycle. Phylogenetic analysis was conducted with closely related
      microsporidia from mosquitoes. Hyalinocysta chapmani did not cluster within
      described Amblyospora species and can be considered a sister group, warranting
      separate genus status.

PMID- 12188228
TI  - Military medicine: establishing a more comprehensive strategy for improved worker
      health.
AB  - In an era of decreased resources, optimizing worker safety and health has become
      increasingly challenging. Data obtained from the Army and Navy Safety Centers
      suggest that current strategies for managing worker safety and health can be
      improved. In the past, work safety management practices placed sole
      responsibility for safety upon the worker. More recently, safety and health
      practices have recognized that organizational climate and structure influence
      worker safety and health. Furthermore, although worker safety and health, work
      site health promotion, and risk management efforts have been managed
      autonomously, all three components are interrelated and dependent on one another
      to achieve greater worker safety and health. The intent of this article is to
      increase awareness and marketing among military medicine staff members of the
      crucial components of an improved health and safety program. This article
      explains common organizational barriers to achieving worker safety and health,
      provides an understanding of the interconnectedness of occupational safety and
      health, health promotion, and risk management, and suggests strategies for
      optimizing worker safety and health.

PMID- 12188229
TI  - Effect of thermocycling on the fracture strength of intact third molars stored
      for two different time periods.
AB  - OBJECTIVE: This study investigated the effect of thermocycling on the fracture
      strength of intact, extracted molars stored for two different intervals before
      testing. METHODS: Thirty-eight recently extracted molars and 38 molars stored for
      1 to 5 years were each randomly separated to create four subgroups. One subgroup
      from each storage interval was thermocycled 1,000 times from 5 to 55 degrees C
      using 30-second dwell times, and then all teeth were fractured using a universal
      testing machine. RESULTS: Thermocycled recently extracted molars had
      significantly lower mean fracture strengths than nonthermocycled recently
      extracted molars (p < 0.001). No other pairwise comparisons were statistically
      significant. CONCLUSION: Thermocycling significantly reduced the fracture
      strength of recently extracted third molars. However, no significant differences
      in fracture strength were seen with molars stored for 1 to 5 years before
      thermocycling.

PMID- 12188230
TI  - The quantitative analysis of depleted uranium isotopes in British, Canadian, and
      U.S. Gulf War veterans.
AB  - The purpose of this work was to determine the concentration and ratio of uranium
      isotopes in allied forces Gulf War veterans. The 27 patients had their 24-hour
      urine samples analyzed for 234U, 235U, 236U, and 238U by mass spectrometry. The
      urine samples were evaporated and separated into isotopic dilution and
      concentration fraction by the chromatographic technique. The isotopic composition
      was measured by a thermal ionization mass spectrometer using a secondary electron
      multiplier detector and ion-counting system. The uranium blank control and SRM960
      U isotopic standard were analyzed by the same procedure. Statistical analysis was
      done by an unpaired t test. The results confirm the presence of depleted uranium
      (DU) in 14 of 27 samples, with the 238U:235U ratio > 207.15. This is
      significantly different from natural uranium (p < 0.008) as well as from the DU
      shrapnel analysis, with 22.22% average value of DU fraction, and warrants further
      investigation.

PMID- 12188231
TI  - Laboratory conditions and safety in a chemical warfare agent analysis and
      research laboratory.
AB  - Toxic chemicals have been used as weapons of war and also as means of terrorist
      attacks on civilian populations. Research focusing on chemical warfare agents
      (CWAs) may be associated with an increased risk of exposure to and contamination
      by these agents. This article summarizes some of the regulations concerning
      designation and safety in a CWA analysis and research laboratory and medical
      countermeasures in case of an accidental exposure. The design of such a
      laboratory, coupled with a set of safety guidelines, provides for the safe
      conduct of research and studies involving CWAs. Thus, a discussion of
      decontamination and protection means against CWAs is also presented.

PMID- 12188232
TI  - Satisfaction among soldiers with secondary medical services within military and
      civilian clinical settings.
AB  - The medical services system of the Israel Defense Forces (IDF) is founded on a
      principle that by definition considers it the military's role to maintain the
      health of its personnel in uniform. The 1994 Compulsory Health Insurance Law,
      Section 55 addresses health services for soldiers, stating that a soldier is
      entitled to health services from the Medical Corps of the IDF or an agent
      operating on its behalf. In the implementation of its responsibilities, the IDF
      Medical Corps operates an array of medical services, including secondary care.
      This study deals with the scope of utilization of secondary medical services by
      IDF personnel visiting military medical clinics and civilian hospital outpatient
      clinics: their character, the subjective health status of the respondents, and
      their degree of satisfaction with medical services. The results indicate that
      most of those seeking medical treatment at military and civilian clinics are not
      chronically ill. Most consider their health status to be good to excellent, but
      many of those referred for secondary care--more than half of the respondents who
      visited military specialist clinics-visited the clinics many times and even
      visited other clinics. No problem of access to clinics was found, but
      availability was problematic. There was a marked preference among patients to
      receive secondary health sevices from outside civilian agents rather than the
      military system.

PMID- 12188233
TI  - Positive predictive value of a health history questionnaire.
AB  - The U.S. Air Force Academy (USAFA) is one of the nation's military universities,
      with the mission to educate and motivate cadets to be career Air Force officers.
      This diverse population arrives at the USAFA with varying immunization records
      and disease histories. Analyses of costs and benefits regarding immunization
      strategies rely on accurate data and assumptions used in their calculation.
      Health history questionnaires are a low-cost way of evaluating immunization and
      disease history. However, this requires a good estimate of the questionnaire's
      positive predictive value, which may vary among populations. This study attempts
      to provide a more accurate estimate of the positive predictive value of health
      history questionnaires regarding varicella and rubella disease and vaccination
      strategies for the population of fourth degree (freshman) cadets at the USAFA. We
      found positive predictive values of 99% for rubella and 86% for varicella. These
      data emphasize the importance of analyzing the specific population for which a
      program is intended rather than broadly applying recommendations that were
      developed in other populations.

PMID- 12188234
TI  - Prevalence of Blastocystis hominis carriage in Thai army personnel based in
      Chonburi, Thailand.
AB  - Blastocystis hominis is one of the most common intestinal parasites found in
      humans. The prevalence of B. hominis carriage in personnel who worked in the
      First Army Support Command, Chonburi, Thailand, was determined. Forty-four
      percent of 616 stool samples were positive for B. hominis using both simple smear
      and concentration (Formalin/ethyl acetate) techniques. The usefulness of the
      concentration technique in the diagnosis of B. hominis has been confirmed. Of 272
      positive specimens, 75% were detected by simple smear and 25% were additionally
      identified by the concentration technique. The prevalence of B. hominis carriage
      was highest among the privates who had lived longest in this command. This
      finding indicates that they might have acquired B. hominis during their stay at
      this base. The significantly high prevalence of B. hominis carriage was found in
      the Ordnance Ammunition Battalion. In this battalion, privates who had education
      lower than the secondary school level had significantly greater risk of B.
      hominis carriage.

PMID- 12188235
TI  - An evaluation of provocative testing in the diagnosis of carpal tunnel syndrome.
AB  - Carpal tunnel syndrome is a commonly known neurological entrapment disorder seen
      by primary care providers and occupational therapists. The purposes of this pilot
      study were to (1) identify the evaluation methods that primary care providers and
      occupational therapists use to diagnose carpal tunnel syndrome; (2) describe the
      procedures for evaluations that practitioners use in common; and (3) compare the
      frequencies of diagnostic results achieved with nerve conduction velocity testing
      vs. provocative testing. Three family care practitioners, two physician
      assistants, and four occupational therapists at four clinical sites participated
      over 4 months. Fifty-five subjects' hands (77 hands; 22 bilateral) were examined.
      Patients' ages ranged from 24 to 61 years, with mean of 42.5 years. Chi2 and
      Fisher's exact tests were used to examine diagnostic results. Practitioners
      differed slightly in evaluation methods and procedures used. The Tinel's sign
      results agreed with 57% (motor) and 64% (sensory) of positive nerve conduction
      velocity results (p > 0.05), whereas Phalen's test agreed with 83% (motor) and
      85% (sensory) (p < 0.05). Although these results indicate that Phalen's test is
      more sensitive, they also accentuate the need for standardized testing based on
      the proposed use of the test results (screening vs. treatment).

PMID- 12188236
TI  - Humanitarian assistance in UN operations: laboratory and consultative support of
      a local hospital in Eritrea.
AB  - The United Nations Mission to Eritrea and Ethiopia deployed to monitor a cease
      fire in a mutually agreed upon Temporary Security Zone. Support for the United
      Nations (UN) troops included a Field Dressing Station supplied by the Dutch Navy,
      augmented by Canadian personnel. As with most missions of this type, the health
      of the deployed Canadian and Dutch soldiers is such that there is time to provide
      some medical support to local civilian institutions. This article describes this
      interaction in Eritrea through the illustration of the diagnosis and management
      of a specific illness through the cooperative use of high-technology laboratory
      equipment coupled with what we believe to be common sense. Although there was no
      specific United Nations Mission to Eritrea and Ethiopia humanitarian medical
      assistance mandate, the expanded use of CIMIC# projects was employed to allow
      this activity. The guiding principle of sustainability once UN facilities leave
      is also illustrated in the approach taken to provide this assistance.

PMID- 12188237
TI  - Evaluation of fiberglass versus plaster of Paris for immobilization of fractures
      of the arm and leg.
AB  - We conducted a prospective randomized study comparing the costs, comfort, and
      effects on activities of daily living of fractures managed in plaster of Paris
      (POP) vs. fiberglass (FG) for at least 4 weeks. A total of 183 patients with
      short arm and short leg casts were evaluated. Twenty-seven patients were
      excluded, leaving 156 patients in the study. The average cost per fracture
      immobilized in a short arm cast was $12.90 for POP and $15.45 for FG. For short
      leg casts, the average cost of immobilization was $49.06 for POP and $47.85 for
      FG. FG had a significantly lower breakdown rate in short leg casts (17% vs. 66%)
      but not in short arm casts. In 21 measures of activities of daily living and
      comfort, FG short arm casts were significantly better than POP in only the weight
      of the cast (p = 0.01). FG short leg casts were superior to POP in getting
      dressed, odor, sweating under the cast, work/school accomplishments, and overall
      fewer restrictions and comfort.

PMID- 12188238
TI  - Physical therapy and changes in disability for patients with low back pain.
AB  - OBJECTIVE: The purpose of this study was to describe the changes in disability
      for patients being treated for low back pain (LBP) at a military physical therapy
      clinic from the time of initial evaluation to discharge from physical therapy and
      to compare those changes across categories of symptom duration and location.
      METHODS: Three hundred four consecutive patients who completed a course of
      physical therapy for LBP were evaluated with the Oswestry LBP Disability
      questionnaire at the time of initial evaluation and discharge from physical
      therapy. RESULTS: In all of the patient groups, mean Oswestry scores had
      decreased significantly from the time of initial evaluation to discharge from
      physical therapy, indicating that patients experienced significantly decreased
      levels of disability at the time of discharge from physical therapy. However,
      patients with LBP without lower extremity symptoms generally had greater
      decreases in disability than patients with LBP with lower extremity symptoms.
      Furthermore, whereas patients in the acute groups had the greatest decrease in
      disability, patients in the chronic groups had the smallest decrease in
      disability. CONCLUSION: Clinicians should use LBP symptom duration, as well as
      the presence or absence of lower extremity symptoms, to assist in developing
      treatment prognoses for patients with LBP.

PMID- 12188239
TI  - Cerebrospinal fluid fistula as a consequence of war head injury.
AB  - Cerebrospinal fluid (CSF) fistula as a consequence of brain missile injury and
      following infectious complications has been recognized for years. Different
      methods of treatment have been advocated. Missiles used in war cause extensive
      destruction of the skull and brain as a result of their high kinetic energy. On
      its transfer through the skull, such high kinetic energy causes fractures called
      "discontinuous fractures," which are distant from the entry wound and not related
      to the fracture of the vault. The role of the timely diagnosis of CSF fistulas
      and their early repair in the management of these wounds is emphasized. Data on
      312 patients with missile injuries of the brain inflicted during the war in
      Croatia were retrieved and analyzed, with special reference to the complications
      of CSF fistulas and infection. Forty-five patients developed CSF fistula, 15
      (33%) of them at the wound site, 23 (51%) as CSF rhinorrhea, and seven (15%) as
      CSF otorrhea. Six patients developed infectious complications. The presented
      strategy and operative approach resulted in a low incidence of infectious
      complications in the study series.

PMID- 12188240
TI  - A conjugate vaccine for the prevention of pediatric pneumococcal disease.
AB  - The use of the pneumococcal 7-valent conjugate vaccine (PCV7 [Prevnar], Wyeth
      Lederle Vaccines), and the impact it is likely to have on pneumococcal disease
      are reviewed. Pneumococcal disease in infants and young children is a major
      health care burden, and the increase in antibiotic resistance among pneumococci
      has complicated disease management. The 23-valent polysaccharide pneumococcal
      vaccines do not protect infants and children younger than 2 years of age. PCV7 is
      effective in this population and should dramatically reduce the incidence of
      invasive pneumococcal disease and have an impact on the incidence of infections
      caused by Streptococcus pneumoniae serotypes present in the vaccine. Research has
      shown that pneumococcal conjugate vaccines reduce nasopharyngeal carriage of
      vaccine serotype S. pneumoniae, including antibiotic-resistant strains. Routine
      immunization is expected to substantially reduce the morbidity and mortality
      associated with invasive pneumococcal disease in children, and coupled with
      expected herd immunity and decreased antibiotic selective pressure, it should
      have a positive impact beyond the immunized population.

PMID- 12188241
TI  - The relationship between life adjustment and parental bonding in military
      personnel with adjustment disorder in Taiwan.
AB  - The aim of the present study was to examine the characteristics of military
      personnel with adjustment disorder to give them more appropriate treatment. The
      participants were 36 military personnel who met the Diagnostic and Statistical
      Manual of Mental Disorders, Fourth Edition, criteria of adjustment disorder as
      diagnosed by a psychiatrist at a teaching hospital in southern Taiwan. Another 24
      persons were recruited as an age-matched control group. Each individual completed
      the clinical interview and the Wechsler Adult Intelligence Scale-Revised and then
      completed the questionnaires which included demographic information, the Parental
      Bonding Instrument, the Eysenck Personality Questionnaire, and the Chinese Health
      Questionnaire. We found statistically significant differences between the case
      and control groups in personality and parental bonding attitudes. Soldiers with
      higher neuroticism, lower extraversion, and maternal overprotection had an
      increased risk of suffering from adjustment disorder. The inclusion of family
      function and the military environment and such other factors as cultural
      variables is recommended for future study. The statistical approach of structural
      equation modeling also should be considered in future studies to determine
      competing risk factors and mediating effects.

PMID- 12188242
TI  - Cardiac injury markers and a failed algorithm: can accurate assessment of acute
      myocardial infarction be cost effective?
AB  - CONTEXT: Most studies assessing the use of cardiac injury markers, such as
      cardiac troponin I (cTnI), total creatine kinase (CK Total), and the cardiac
      isoenzyme of CK (CK-MB), agree that cTnI is the most specific test for diagnosing
      acute myocardial infarction (AMI). However, throughout the literature, there are
      ambiguities and contradictions on assay-ordering criteria. Inconsistent ways of
      viewing biochemical assessment of acute chest pain leads to cardiac injury marker
      assay-ordering patterns that can be nonspecific, ambiguous, and costly.
      OBJECTIVE: This study set out to design a cost-effective strategy and to outline
      criteria for ordering cardiac injury marker assays. This is accomplished by
      comparing Madigan Army Medical Center (MAMC) testing patterns to guidelines
      described in recently published prospective hospital studies investigating the
      markers. DESIGN: This was a retrospective study analyzing the patterns of 34,412
      cardiac marker assays performed on 4,861 patients during 1999 and 2000 at MAMC. A
      total of 5,850 assays were run from 1,223 patients during the first 6 months of
      2001. RESULTS: The MAMC chemistry section spent more than $100,000 during 1999
      for the measurement of cardiac injury markers. During 2000, an algorithm was
      implemented to place controls on ordering; however, the same dollar amount was
      spent. CK Total, CK-MB, and cTnI testing represent 3.5% of the tests performed in
      the chemistry section, but they consumed about 20% of the supply budget. This
      disproportionate expenditure is attributable to numerous, dissimilar, and
      voluminous ordering patterns. CONCLUSIONS: Proper use of cardiac marker assays
      can lead to rapid and accurate diagnosis of AMI and subsequently save lives. This
      study demonstrates that cTnI is the only marker needed for accurate and more cost
      effective assessment of AMI.

PMID- 12188243
TI  - Intimate partner violence among U.S. Army soldiers in Alaska: a comparison of
      reported rates and survey results.
AB  - OBJECTIVES: A U.S. Army post in Alaska (Fort A) was determined to have a higher
      than average rate of officially reported cases of spousal abuse compared with the
      Army as a whole. The purpose of the present study was to determine whether Fort A
      had a higher rate of self-reported spousal abuse compared with the Army as a
      whole. METHOD: A survey on intimate partner violence was conducted among 648
      married male personnel who completed a questionnaire that included the Modified
      Conflict Tactic Scale. RESULTS: Comparisons with results of an earlier study
      involving a large representative sample of Army personnel indicated that Fort A
      did not have higher levels of intimate partner violence than the Army average
      based on soldiers' self-reports. CONCLUSION: It may not be appropriate to draw
      conclusions about serious intimate partner violence in the military based solely
      on the results of family conflict surveys.

PMID- 12188244
TI  - Commercial sport drinks versus light meal combat rations: effect on simulated
      combat maneuvers.
AB  - This study compared a light meal combat ration (LMCR) to specific commercial
      sport drinks (CSD) and the effect of their ingestion on time to exhaustion during
      simulated combat maneuvers (SCM). The SCM consisted of three activities: a 2-hour
      march at 50% of maximal aerobic capacity (VO2max); a subsequent 1-hour run at 70%
      VO2max; and a run to exhaustion at 80% VO2max. During SCM, the subjects consumed
      one of four different meals: three CSD (Ergo, Go Sports, and Gatorlode), and the
      LMCR. In addition, one SCM was conducted with half-rations. Oxygen consumption,
      heart rate, and rating of perceived exertion were evaluated during each phase of
      the SCM. Time in minutes (mean +/- SD) to exhaustion at 80% VO2max for Ergo (42.3
      +/- 8.9), Go Sports (39.4 +/- 13.3), and Gatorlode (37.7 +/- 8.6) was not
      significantly different from that for LMCR (36.4 +/- 13.0) but was greater than
      that for half-LMCR (30.3 +/- 9.3). O2 consumption, heart rate, and rating of
      perceived exertion were not affected by meal type but did increase over time for
      each stage of the SCM. We conclude that the amount of calories ingested was
      responsible for the differences noted in time to exhaustion. We further conclude
      that the CSD represent a readily available source of energy and fluid that could
      be used to replace and/or supplement the current LMCR.

PMID- 12188245
TI  - Bladder stone in a 3-year-old Dominican male.
AB  - Bladder stones forming in the absence of underlying uropathy are termed primary,
      or endemic, bladder stones. They are prevalent among children in certain
      developing nations of Asia and northern Africa. Dietary deficiencies have been
      implicated in the cause of such stones, because they occur in regions of
      malnutrition and poverty; yet studies remain inconclusive. Interestingly, reports
      are lacking of primary bladder stones occurring in Central and South America, as
      well as in the Caribbean and Pacific islands, where certainly there are areas of
      impoverishment. The reasons for this remain unclear. This article presents the
      case of a primary bladder stone occurring in a patient from the Dominican
      Republic.

PMID- 12188246
TI  - A case report and a proposed algorithm for the transfer of patients with Stevens
      Johnson syndrome and toxic epidermal necrolysis to a burn center.
AB  - Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are rare
      cutaneous diseases marked by substantial epidermal denudation and are often
      complicated by sepsis and multiple organ failure. They are most commonly caused
      by drug therapy. Patients afflicted with these diseases require care that may
      exhaust the capabilities of medicine wards and medical intensive care units
      alike; however, their mortality is reduced when treated at burn centers, which
      are better equipped to treat extensive skin denudation. We report a case of TEN
      and propose an algorithm to provide guidance for making the critical decision to
      transfer patients with SJS and TEN to burn units.

PMID- 12188247
TI  - Characterization and use of ultrasound contrast agents.

PMID- 12188248
TI  - Detection of individual microbubbles of an ultrasound contrast agent: fundamental
      and pulse inversion imaging.

PMID- 12188249
TI  - Ultrasound imaging with SonoVue: low mechanical index real-time imaging.

PMID- 12188250
TI  - Multi-modal contrast agents: a first step.

PMID- 12188251
TI  - Blood contrast enhancement with a novel, non-gaseous nanoparticle contrast agent.

PMID- 12188252
TI  - In vivo ultrasound imaging of thrombi using a target-specific contrast agent.

PMID- 12188253
TI  - Dy-complexes as high field T2 contrast agents: influence of water exchange rates.
AB  - Dy complexes can act as suitable negative (T2) contrast agents for Magnetic
      Resonance Imaging (MRI). As clinical MRI moves toward higher fields, tuning of
      the exchange rate of coordinated water molecules will become necessary to
      optimize the r2 relaxivity. For Dy complexes, this will require lengthening of
      the water residence time, a strategy opposite that required to optimize the r1
      relaxivity of Gd complexes. However, very slow water exchange can be deleterious.
      This is illustrated here by a Dy complex that is characterized by a very slow
      water exchange. This complex, Dy-DOTA-4AmCE, is compared with several Dy-DTPA
      derivatives known for their efficacy as T2 contrast agents at high magnetic
      fields.

PMID- 12188254
TI  - Synthesis and physicochemical characterization of 1,4,7,10-tetra (2-glutaryl)
      1,4,7,10 tetraazacyclododecane lanthanide complexes.

PMID- 12188255
TI  - Crosslinked iron oxides (CLIO): a new platform for the development of targeted MR
      contrast agents.

PMID- 12188256
TI  - Preclinical characterization of monomer-stabilized very small superparamagnetic
      iron oxide particles (VSOP) as a blood pool contrast medium for MR angiography.

PMID- 12188257
TI  - Annexin V-CLIO: a nanoparticle for detecting apoptosis by MRI.

PMID- 12188258
TI  - MR lymphangiography for detection of minimal nodal disease in patients with
      prostate cancer.

PMID- 12188259
TI  - Molecular imaging of MMP expression and therapeutic MMP inhibition.

PMID- 12188260
TI  - Imaging folate binding protein expression with MRI.

PMID- 12188261
TI  - Cyanine dyes as contrast agents in biomedical optical imaging.

PMID- 12188262
TI  - Imaging cathepsin B up-regulation in HT-1080 tumor models using fluorescence
      mediated molecular tomography (FMT).

PMID- 12188263
TI  - Can a small-molecular gadolinium contrast agent be applied successfully with
      dynamic MRI to quantitatively define brain tumor microvascular responses to
      angiogenesis inhibition?

PMID- 12188265
TI  - Molecular imaging and targeted drug delivery with a novel, ligand-directed
      paramagnetic nanoparticle technology.

PMID- 12188264
TI  - Assessing perfusion and capillary permeability changes induced by a VEGF
      inhibitor in human tumor xenografts using macromolecular MR imaging contrast
      media.

PMID- 12188266
TI  - Monitoring stem cell therapy in vivo using magnetodendrimers as a new class of
      cellular MR contrast agents.

PMID- 12188267
TI  - Evaluation of the time window for Resovist-enhanced T2-weighted MRI of the liver.

PMID- 12188269
TI  - Contrast enhanced MRI of stunned myocardium using Mn-based MRI contrast media.

PMID- 12188268
TI  - USPIO-enhanced direct thrombus MRI.

PMID- 12188271
TI  - Gadobenate dimeglumine (Multihance) in magnetic resonance mammography.

PMID- 12188270
TI  - Comparison between gadopentetate and feruglose (Clariscan)-enhanced MR
      mammography: preliminary clinical experience.

PMID- 12188272
TI  - Spectrally inhomogeneous effects of contrast agents in breast lesion detected by
      high spectral and spatial resolution MRI.

PMID- 12188273
TI  - Polyethylene glycol solution as an oral contrast agent for MR imaging of the
      small bowel.

PMID- 12188274
TI  - Evaluation of simethicone coated cellulose (SonoRx) as a negative oral contrast
      agent for abdominal-pelvic computed tomography.

PMID- 12188275
TI  - CT pulmonary angiography and perfusion: an experimental study using blood pool
      and nonspecific contrast agent.

PMID- 12188277
TI  - Dynamic contrast-enhanced computed tomography (CT) for quantitative estimation of
      microvascular permeability in human brain tumors.

PMID- 12188276
TI  - Optimization of contrast agent administration in MSCT angiography.

PMID- 12188278
TI  - Dynamic contrast-enhanced functional imaging with multi-slice CT.

PMID- 12188279
TI  - Ultrasound imaging of focal liver lesions with a second-generation contrast
      agent.

PMID- 12188280
TI  - Characterization of focal liver lesions with phase inversion ultrasound during
      the late liver-specific phase of Levovist.

PMID- 12188281
TI  - Characterization of focal liver lesions with pulse inversion harmonic imaging
      (PIHI) using a second generation US contrast agent.

PMID- 12188282
TI  - The first phase I study of a novel ultrasound contrast agent (BR14): assessment
      of safety and efficacy in liver and kidneys.

PMID- 12188283
TI  - Therapeutic effect of chemoembolization therapy on hepatocellular carcinoma:
      evaluation with contrast-enhanced power Doppler sonography and contrast-enhanced
      harmonic imaging.

PMID- 12188284
TI  - 3D-power Doppler ultrasound of breast lesions with a microbubble contrast agent.

PMID- 12188285
TI  - Assessment of brain perfusion with echo contrast specific imaging modes and
      Optison.

PMID- 12188286
TI  - Contrast enhanced intermittent power Doppler ultrasound with sub-micron bubbles
      for sentinel node detection.

PMID- 12188287
TI  - Paradigms and perspectives in contrast media research.

PMID- 12188288
TI  - Peripheral run-off CE-MRA with a 1.0 molar gadolinium chelate (Gadovist) with
      intraarterial DSA comparison.

PMID- 12188289
TI  - Gadomer-17 enhanced navigator-echo MRA: experimental study and initial results.

PMID- 12188290
TI  - B22956/1, a new intravascular contrast agent for MRI: first administration to
      humans--preliminary results.

PMID- 12188291
TI  - MR angiography with a new rapid clearance blood pool agent (P792): initial
      experience in rabbits.

PMID- 12188292
TI  - Gadobenate dimeglumine (Multihance) in contrast-enhanced magnetic resonance
      angiography.

PMID- 12188293
TI  - Early distribution dynamics of polymeric magnetic resonance imaging contrast
      agents in rats.

PMID- 12188294
TI  - Influence of contrast media dose in elliptical ordered MR angiography image
      quality of the carotid arteries: preliminary results.

PMID- 12188295
TI  - Comparison of Gd-BOPTA and Gd-DOTA for peripheral CE-MRA: a double-blind clinical
      study.

PMID- 12188296
TI  - First-pass and equilibrium phase MRA following intravenous bolus injection of SH
      U 555 C: Phase I clinical trial in elderly volunteers with risk factors for
      arterial vascular disease.

PMID- 12188297
TI  - Magnetic resonance angiography by gasses or gas-containing agents: first
      developments of new types of black blood imaging.

PMID- 12188298
TI  - Anaphylactoid reactions to iodinated contrast media.

PMID- 12188299
TI  - Prevention of generalized reactions to CM.

PMID- 12188300
TI  - The role of oxygen free radicals in contrast induced nephrotoxicity.

PMID- 12188301
TI  - Adverse effects of intra-arterial carbon dioxide on perfusion in vitro and in
      vivo.

PMID- 12188302
TI  - Adding sodium and calcium ions to iodixanol and mannitol: effects on risk of
      ventricular fibrillation after infusion into the left coronary artery of pigs.

PMID- 12188304
TI  - Intrathecal gadolinium-enhanced MR-cisternography: depiction of the
      subarachnoidal space and evaluation of gadobenat-dimeglumin-(Gd-BOPTA,
      "Multihance") toxicity in an animal model and a clinical case.

PMID- 12188303
TI  - Electrocardiographic effects of diagnostic imaging agents.

PMID- 12188305
TI  - Dynamic micro-MRI of liver micrometastasis with a novel liver macromolecular MR
      contrast agent DAB-Am64-(1B4M-Gd)64.

PMID- 12188306
TI  - Hepatic kinetics of MRI contrast agents in the isolated perfused rat liver.

PMID- 12188307
TI  - Safety and efficacy of a novel hepatobiliary MR contrast agent GN-1140 (Gd-DTPA
      DeA): from the results of phase I and phase II clinical trials.

PMID- 12188308
TI  - Liver lesion detection and characterization with sequential use of hepatobiliary
      contrast agent mangafodipir trisodium and gadolinium-DTPA in a single imaging
      protocol.

PMID- 12188309
TI  - Gadodiamide and gadopentetate dimeglumine in MRI versus spiral CT in the
      diagnosis of liver lesions.

PMID- 12188310
TI  - Double contrast MR imaging of hepatocellular carcinoma evaluating lesion
      detection and conspicuity.

PMID- 12188311
TI  - Quantitative assessment of the contrast behavior of typical focal hepatic lesions
      before and after the administration of Gd-DTPA and superparamagnetic iron oxide
      particles.

PMID- 12188312
TI  - Superparamagnetic iron oxide particle-enhanced hepatic MRI: differentiation of
      hepatic lesions using dual echo field echo sequences without obtaining
      precontrast images.

PMID- 12188313
TI  - Hypervascular hepatic lesions: dynamic and late enhancement pattern with Gd
      BOPTA.

PMID- 12188314
TI  - MRI of antigen-induced arthritis in rabbits: improved contrast and disease
      characterization with the blood pool agent MS-325.

PMID- 12188315
TI  - In vivo magnetic resonance imaging of tissue pH using a novel pH-sensitive
      contrast agent, GdDOTA-4AmP.

PMID- 12188316
TI  - Magnetic intracellular labeling of mammalian cells by combining (FDA-approved)
      superparamagnetic iron oxide MR contrast agents and commonly used transfection
      agents.

PMID- 12188317
TI  - Exploring multifunctional features of necrosis avid contrast agents.

PMID- 12188318
TI  - Preclinical profile and clinical potential of gadocoletic acid trisodium salt
      (B22956/1), a new intravascular contrast medium for MRI.

PMID- 12188319
TI  - Evaluation of water-soluble metallofullerenes as MRI contrast agents.

PMID- 12188321
TI  - Hyperpolarized helium3 encapsulated in microbubbles: a new class of blood pool
      MRI contrast agent.

PMID- 12188320
TI  - Global and regional cerebral blood flow measurements using NMR of injected
      hyperpolarized xenon-129.

PMID- 12188322
TI  - Hyperpolarized 3helium gas as a novel contrast agent for functional MRI of
      ventilation.

PMID- 12188323
TI  - 13C-angiography.

PMID- 12188324
TI  - Tumor microvascular changes to anti-angiogenic treatment assessed by MR contrast
      media of different molecular weights.

PMID- 12188325
TI  - Correlating subcellular contrast agent location from dynamic contrast-enhanced
      magnetic resonance imaging (dMRI) and analytical electron microscopy.

PMID- 12188326
TI  - MRI monitoring of tumor response to a novel VEGF tyrosine kinase inhibitor in an
      experimental breast cancer model.

PMID- 12188327
TI  - Comparison of the tumoral biodistribution of P792, a rapid clearance blood pool
      agent and Gd-DOTA in a C6 glioma cerebral tumor model in rats.

PMID- 12188328
TI  - Gd-labeled liposomes for monitoring liposome-encapsulated chemotherapy:
      quantification of regional uptake in tumor and effect on drug delivery.

PMID- 12188329
TI  - Gadolinium contrast media for DSA in azotemia: are they really safer than
      iodinated agents?

PMID- 12188330
TI  - Nephrotoxicity after renal angiography using iodine and gadolinium contrast media
      in pigs with renal damage.

PMID- 12188331
TI  - Two-center clinical study on the effect of chronic renal impairment on safety of
      iopromide 300 mg iodine/ml.

PMID- 12188332
TI  - Enhanced radio sensitivity with iodinated contrast agents using monochromatic
      synchrotron X-rays on human cancerous cells.

PMID- 12188333
TI  - Treatment of iodinated contrast material extravasation with hyaluronidase.

PMID- 12188334
TI  - Tracking national toxic exposure and illness.

PMID- 12188335
TI  - China's pollution progress slows.

PMID- 12188336
TI  - U.S. rule could increase e-waste exports.

PMID- 12188337
TI  - Mercury pollution may contribute to antibiotic resistance.

PMID- 12188338
TI  - 2002 green chemistry awards.

PMID- 12188339
TI  - Baltics blame Russia for high risk of toxic blooms.

PMID- 12188340
TI  - The evolution of refuse incineration.

PMID- 12188341
TI  - Wet deposition of polychlorinated biphenyls in urban and background areas of the
      Mid-Atlantic States.
AB  - Spatial and temporal trends of polychlorinated biphenyl (PCB) concentrations in
      precipitation were measured at urban and background sites as part of the New
      Jersey Atmospheric Deposition Network (NJADN). The volume weighted mean
      concentration (VWM) of sigmaPCBs (sum of PCBs) based on precipitation
      measurements at three background sites was in the range of 0.30-0.50 ng/L.
      Concentrations in precipitation at two urban-industrial sites were on average 7
      43 times higher than background concentrations. Wet deposition fluxes of
      sigmaPCBs at the two urbanized sites were 16 +/- 3.4 and 3.9 +/- 0.72 microg/m2
      yr, while the background flux was approximately 0.30 microg/m2-yr. On average,
      97% of the total atmospheric washout (WT) of PCBs resulted from particle
      scavenging. The fraction of atmospheric PCBs on particles was the best predictor
      of atmospheric washout in both urban (log WT = 0.71 (+/- 0.049) log psi + 4.9 (+/
      0.11); r2 = 0.81) and nonurban areas (log W(T) = 0.77 (+/- 0.083) log psi + 5.6
      (+/- 0.16); r2 = 0.64). Wet deposition fluxes of sigmaPCBs are of the same order
      of magnitude as dry-particle deposition fluxes in all land-use regimes.

PMID- 12188342
TI  - Perfluorooctanesulfonate and related fluorinated hydrocarbons in marine mammals,
      fishes, and birds from coasts of the Baltic and the Mediterranean Seas.
AB  - Perfluorooctanesulfonate (PFOS; C8F17SO3-), perfluorooctanesulfonamide (FOSA;
      C8F17SO2NH2), perfluorohexanesulfonate (PFHxS; C6F13SO3-), and perfluorooctanoate
      (PFOA; C7F15CO2-) were detected in 175 samples of liver and blood of bluefin tuna
      (Thunnus thynnus), swordfish (Xiphias gladius), common cormorants (Phalacrocorax
      carbo), bottlenose dolphins (Tursiops truncatus), striped dolphins (Stenella
      coeruleoalba), common dolphins (Delphinus delphi), fin whales (Balenoptera
      physalus), and long-finned pilot whales (Globicephala melas) from the Italian
      coast of the Mediterranean Sea and in livers of ringed seals (Phoca hispida),
      gray seals (Halichoerus grypus), white-tailed sea eagles (Haliaeetus albicilla),
      and Atlantic salmon (Salmo salar) from coastal areas of the Baltic Sea. PFOS was
      detected in all of the wildlife species analyzed. Concentrations of PFOS in blood
      decreased in order of bottlenose dolphins > bluefin tuna > swordfish. Mean PFOS
      concentrations (61 ng/ g, wet wt) in cormorant livers collected from Sardinia
      Island in the Mediterranean Sea were less than the concentrations of PFOA (95
      ng/g, wetwt). PFOS concentrations in cormorant livers were significantly
      correlated with those of PFOA. FOSA was found in 14 of 19 livers or blood samples
      of marine mammals from the Mediterranean Sea. The highest concentration of 878 ng
      FOSA/g, wet wt, was found in the liver of a common dolphin. Livers of ringed and
      gray seals from the Bothnian Bay in the Baltic Sea contained PFOS concentrations
      ranging from 130 to 1,100 ng/g, wet wt. No relationships between PFOS
      concentrations and ages of ringed or gray seals were observed. Concentrations of
      PFOS in livers of seals were 5.5-fold greater than those in corresponding blood.
      A significant positive correlation existed between the PFOS concentrations in
      liver and blood, which indicates that blood can be used for nonlethal monitoring
      of PFOS. Trend analysis of PFOS concentrations in livers of white-tailed sea
      eagles collected from eastern Germany and Poland since 1979 indicated an increase
      in concentrations during the 1990s. Livers of Atlantic salmons did not contain
      quantifiable concentrations of any of the fluorochemicals monitored. PFOS is a
      widespread contaminant in wildlife from the Baltic and the Mediterranean Seas,
      while FOSA and PFOA were detected only in certain locations indicating their
      sporadic spatial distribution.

PMID- 12188343
TI  - Spectrofluorescence of sediment humic substances and historical changes of
      lacustrine organic matter provenance in response to atmospheric nutrient
      enrichment.
AB  - Humic substances were extracted from the sediments of two small alpine lakes in
      the Colorado Front Range and characterized by three-dimensional fluorescence
      spectroscopy. The fluorescence index (FI), defined as the ratio of fluorescence
      emitted at 450 nm to that emitted at 500 nm from an excitation wavelength of 370
      nm, was computed and thereafter compared to additional sediment proxies of recent
      environmental change. Stratigraphic changes in both sediment C:N ratios and
      diatom assemblages parallel those of Fl, together indicating pronounced increases
      in the contribution of autochthonous organic matter to lake sediments since the
      mid-20th century. This result is consistent with increased algal production
      attributable to nutrient enrichment, given thatthe region undergoes episodic
      nitrogen saturation in response to anthropogenic N emission. The validation of
      sediment Fl measurements through comparisons with independent methods
      demonstrates the utility of this technique for characterizing shifts in the
      provenance of lake sediment organic matter arising from changing environmental
      conditions.

PMID- 12188344
TI  - Air-side and plant-side resistances influence the uptake of airborne PCBs by
      evergreen plants.
AB  - The transfer of persistent organic pollutants (POPs) from airto vegetation is an
      important air-surface exchange process that affects global cycling and can result
      in human and wildlife exposure via the terrestrial food chain. To improve
      understanding of this process, the uptake of gas-phase polychlorinated biphenyls
      (PCBs) by two slow-growing evergreen shrubs, Skimmia japonicaThunb. and
      Hebe"Great Orme", was studied to investigate the influence of air-side and plant
      side resistances. Uptake of PCBs was monitored over periods of hours, days, and
      weeks. Uptake rates were higher in the smaller Hebe leaves than the Skimmia
      leaves. Equilibrium was not attained between air and plants in the duration of
      the experiments; uptake curves were indicative of a two-phase uptake-step 1 over
      the order of hours and step 2 continuing steadily over days to weeks. Uptake
      rates (h(-1)) were greater in conditions simulating typical ambient wind speeds
      (2 m s(-1)) than under still air, indicating a significant impact of air-side
      resistance relative to plant-side resistance in still air. Wind speed is an
      important variable that has not been previously considered in studies of the air
      planttransfer of persistent organic pollutants (POPs). Uptake rate constants
      increased with increasing level of chlorination (and hence K(OA)) both in still
      air and under turbulent conditions. This was inconsistent with the idea of air
      side resistance dominating uptake, since diffusion rates in air decrease with
      molecular weight (and hence KOA). Greater uptake of particle-bound PCBs may have
      contributed to this finding, but the most likely explanation is the previously
      established relationship that the permeability of cuticles increases with
      increasing KOA of the diffusing chemical. The findings indicate that plant-side
      resistance can have an important effect on uptake rates of different PCB
      congeners in the field, even when air-side resistance is high.

PMID- 12188345
TI  - Transboundary atmospheric lead pollution.
AB  - A high-temporal resolution collection technique was applied to refine aerosol
      sampling in Jerusalem, Israel. Using stable lead isotopes, lead concentrations,
      synoptic data, and atmospheric modeling, we demonstrate that lead detected in the
      atmosphere of Jerusalem is not only anthropogenic lead of local origin but also
      lead emitted in other countries. Fifty-seven percent of the collected samples
      contained a nontrivial fraction of foreign atmospheric lead and had 206Pb/207Pb
      values which deviated from the local petrol-lead value (206Pb/207Pb = 1.113) by
      more than two standard deviations (0.016). Foreign 206Pb/207Pb values were
      recorded in Jerusalem on several occasions. The synoptic conditions on these
      dates and reported values of the isotopic composition of lead emitted in various
      countries around Israel suggest that the foreign lead was transported to
      Jerusalem from Egypt, Turkey, and East Europe. The average concentration of
      foreign atmospheric lead in Jerusalem was 23 +/- 17 ng/m3, similar to the average
      concentration of local atmospheric lead, 21 +/- 18 ng/ m3. Hence, the load of
      foreign atmospheric lead is similar to the load of local atmospheric lead in
      Jerusalem.

PMID- 12188346
TI  - Determination of longitudinal dispersion coefficient and net advection in the
      tidal hudson river with a large-scale, high resolution SF6 tracer release
      experiment.
AB  - Physical processes such as advection, dispersion, and air-water gas exchange play
      important roles in determining the movement and change in concentration of
      contaminants discharged into rivers. In the following, we report results from a
      large-scale SF6 tracer release experiment conducted in the tidal Hudson Riverto
      examine longitudinal dispersion and net advection. SF6 was injected into the
      Hudson River near Newburgh, NY, and surveyed for 13 days using a new, fully
      automated, high-resolution SF6 sampling and analysis system. Net down river
      advection of the water body originally tagged with SF6 was slow, averaging mean
      displacement rates of about 0.5 +/- 0.2 km d(-1). In contrast, spreading of the
      tracer was driven by tidal movement, causing rapid mixing of the water up and
      down river. By examining the change in the second moment of the tracer
      distribution with time, we determined the mean longitudinal dispersion
      coefficient to be 70.1 +/- 4.3 m2 s(-1). Temporal evolution of the SF6 inventory
      indicates an average gas transfer velocity over the period of the experiment of
      6.5 +/- 0.5 cm h(-1) (1.56 +/- 0.12 m d(-1)). Vertical profiles show that mixing
      into the bottom layers of the river, in places reaching more than 53 m, seemed to
      be rapid.

PMID- 12188347
TI  - Connecting atmospheric nitrogen deposition to coastal eutrophication.

PMID- 12188348
TI  - Atmospheric nitrogen deposition to estuares in the mid-Atlantic and northeastern
      United States.
AB  - The purpose of this work was to determine the contribution made by atmospheric
      nitrogen (N) deposition to the total N input to 10 estuaries on the east coast of
      the United States. We estimated the amount of N fixed by human activities in the
      watersheds (N fertilization, biotic N2fixation by legumes and pastures,
      atmospheric N deposition, and net food and feed import of N) of these 10
      estuaries and used a land-use specific approach to estimate the N available for
      transport to the estuary from different watershed N sources (runoff from
      agriculture, urban areas and upland forests, point sources, and atmospheric
      deposition). Total atmospheric N inputs (watershed runoff plus direct deposition
      to the surface of estuary) accounted for 15-42% of the total N inputs to these 10
      estuaries. Direct deposition to the surface of the estuary was an important
      atmospheric N source for four estuaries, accounting for 35-50% of the total
      atmospheric N inputs. Simulated reductions of atmospheric N deposition by 25% and
      50% of current deposition rates reduced the contribution made by atmospheric N
      deposition to the total N loads by 1-6% and 2-11%, respectively. Largest
      reductions occurred in estuaries with direct atmospheric N deposition
      contributions >35% of the total atmospheric N input. Results from our simulated
      reductions suggest that considerable reductions (>25%) in atmospheric N
      deposition will be needed to significantly reduce the contribution made by
      atmospheric N deposition to the total N loads to our study estuaries. In
      addition, reductions in atmospheric N deposition will first be detected in
      estuaries with relatively high direct deposition inputs of atmospheric N
      deposition.

PMID- 12188349
TI  - Occurrence of stable foam in the upper Rhine River caused by plant-derived
      surfactants.
AB  - For 30 yr, a persistent foam cover has been observed during the summer months in
      the Rhine River beneath the Rhine Fall, a waterfall near Schaffhausen,
      Switzerland. This phenomenon has been a matter of public concern ever since its
      first appearance, but all previous attempts to clarify the origin of this foam
      had remained inconclusive. With the aid of electrospray LC-MS,triterpene saponins
      and mono- and digalactosyldiacylglycerolipids (MGDAG and DGDAG), two classes of
      tensioactive metabolites occurring in the aquatic plant Ranunculus fluitans Lamk.
      (Ranunculaceae), were detected in river water and foam samples. Saponin
      concentrations in water and foam samples were monitored at regular intervals
      during the years 1998 and 2000. Other compound classes with surfactant properties
      such as proteins, humic acids, and synthetic detergents were also analyzed. Foam
      occurrence paralleled with saponin concentration and with the amounts of detached
      Ranunculus biomass accumulating at the dam of the hydroelectric power plant of
      Schaffhausen located just above the Rhine Fall but not with the concentration of
      synthetic detergents. The ecotoxicological potential of Ranunculus constituents,
      water, and foam samples was checked with a representative range of aquatic
      indicator organisms. No acute toxicity was observed at concentrations that were
      at least 50-fold higher than those found in the environmental samples.

PMID- 12188350
TI  - New technique for estimating thresholds of toxicity in ecological risk
      assessment.
AB  - The use and utility of the no observed effect concentration (NOEC) in ecological
      risk assessment is a contentious issue. One concern is that the NOEC is not
      representative of a concentration at which no biologically significant effect is
      occurring. A new method has been developed to estimate the threshold of toxicity,
      or a true NOEC, for aquatic plants. The method involves determining the effective
      concentration (ECx) of a number of endpoints from one species. These ECx values
      are plotted on a log-probability scale. The x-intercept, or a low centile, of the
      distribution can be interpreted as the threshold of toxicity for that plant at
      that response level. This threshold is the concentration at which no effects
      should be observed for any endpoint above that response level. It is based on the
      assumptions that multiple effect measures from a single species will be log
      normally distributed and thatthe distribution contains all possible endpoints for
      that species. The thresholds and the distributions can then be used as a
      substitute for the NOEC or ECx in risk assessment techniques, such as hazard
      quotients and probabilistic ecological risk assessment. This new method of
      estimating toxicitythresholds is more realistic than the use of arbitrary
      uncertainty factors, is more conservative than current probabilistic risk
      assessment methods, allows for simple comparison between species and exposure
      duration to a toxicant, and may be useful for assessing mixture toxicity. This
      technique was applied to field derived data with Lemna gibba, Myriophyllum
      spicatum, and M. sibiricumto assess potential risks from monochloroacetic acid
      (MCA). Using this new risk assessment method, we conclude that MCA does not
      appear to pose a risk to aquatic macrophytes under field conditions at current
      environmental concentrations.

PMID- 12188351
TI  - Degradation of dicarboxylic acids (C2-C9) upon liquid-phase reactions with O3 and
      its atmospheric implications.
AB  - Aerosols are considered major players in climate change and represent health
      hazards. Dicarboxylic acids are among a major class of components that form
      secondary organic atmospheric aerosols. To understand the atmospheric
      transformation of these compounds, kinetic studies on the ozonolysis and the
      photoinduced ozonolysis (lambda > or = 250 nm) of aqueous solutions of seven (C2
      C9) dicarboxylic acids, which have been identified in atmospheric aerosols, were
      performed using Fourier transform infrared and ultraviolet-visible spectroscopy.
      The measured apparent rate constants for dicarboxylic acids in 0.1 mol L(-1)
      aqueous solutions at 298 +/- 2 K are as follows: oxalic, (2.7 +/- 0.1) x 10(-2);
      malonic, (5.5 +/- 0.1); succinic, (6.7 +/- 0.4) x 10(-4); glutaric, (1.3 +/- 0.2)
      x 10(-3); adipic, (1.7 +/- 0.1) x 10(-3); pimelic, (4.4 +/- 0.1) x 10(-3); and
      pinic, (2.5 +/- 0.1) x 10(-2) (L mol(-1) s(-1)). An empirical equation is
      provided to estimate the ozonolysis rate constant of dicarboxylic acids
      containing more than three carbon atoms for which no experimental data exists. A
      mechanism for malonic acid ozonolysis, which explains its fast ozonolysis rate
      constant, is also suggested. The implications of our results to atmospheric
      chemistry indicate that ozonolysis and photoinduced ozonolysis are not
      significant removal pathways for dicarboxylic acids.

PMID- 12188352
TI  - Carbon isotope fractionation during permanganate oxidation of chlorinated
      ethylenes (cDCE, TCE, PCE).
AB  - Permanganate oxidation of chlorinated ethylenes is an attractive technique to
      effect remediation of these important groundwater contaminants. Stable carbon
      isotope fractionation associated with permanganate oxidation of trichloroethylene
      (TCE), tetrachloroethylene (PCE), and cis-1,2-dichloroethylene (cDCE) has been
      measured, to study the possibility of applying stable carbon isotope analysis as
      a technique to assess the efficacy of remediation implemented by permanganate
      oxidation. Average carbon isotope fractionation factors of alphaTCE = 0.9786,
      alphaPCE = 0.9830, and alphacDCE = 0.9789 were obtained, although the
      fractionation factor for PCE may be interpreted to change from a value of 0.9779
      0.9871 during the course of the reaction. The fractionation factors for all three
      compounds are quite similar, in contrast to the variation of fractionation
      factors vs degree of chlorination observed for other degradative processes, such
      as microbial dechlorination. This may be due to a common rate-determining step
      for permanganate oxidation of all three compounds studied. The large
      fractionation factors and the relative lack of dependence of the fractionation
      factors upon other environmental factors (e.g. oxidation rate, presence of
      multiple contaminants, incomplete oxidation, presence of chloride in solution)
      indicate that monitoring delta13C values of chlorinated ethylenes during
      oxidation with permanganate may be a sensitive, and potentially quantitative,
      technique to investigate the extent of degradation.

PMID- 12188353
TI  - Tissue distribution and depuration of 4-tert-octylphenol residues in the cyprinid
      fish, Scardinius erythrophthalmus.
AB  - Alkylphenols are present in the aquatic environment through the degradation of
      alkylphenolpolyethoxylate surfactants in sewage treatment works. Branched chain 4
      alkylphenols have been shown to retard testicular growth and stimulate
      vitellogenin synthesis in freshwater fish. We conducted in vivo studies in order
      to determine the fate and persistence of radiolabeled 4-tert-octylphenol (tOP) in
      the cyprinid fish, rudd (Scardinius erythrophthalmus). Sexually mature rudd were
      exposed to a concentration of 4.7 microg/L of [14C] tOP in a flow through system
      for 10 days. Radioactive residues were extracted from soft tissues and analyzed
      by radio-high-performance liquid chromatography. tOP accumulated as the major
      residue in muscle, ovary, and testis with bioconcentration factors of 24, 85, and
      169, respectively. tOP residues in blood, gill, kidney, liver, and bile were
      extensively metabolized. Analysis of tOP residues in bile revealed 10 major
      metabolites, which were identified by GC-MS as products of aromatic and aliphatic
      hydroxylation, glucuronidation, and glucosidation. Depuration studies with
      exposed fish placed in clean water for up to 10 days resulted in a rapid loss of
      soluble residues from the tissues with half-lives of between 0.7 and 1.0 days
      (muscle, testis, ovary, gill, blood, kidney), 1.7 days (liver), and 5.9 days
      (bile). A further portion of radioactive residues was extracted from blood, gill,
      kidney, and liver after alkaline digestion, suggesting the formation of
      covalently bound protein adducts in these tissues. This study suggests that
      although para-alkyphenolic xenoestrogens can accumulate in muscle and the gonads
      of adult fish, residues are rapidly depurated from these tissues. Furthermore,
      analysis of the parent alkylphenol in bile, after hydrolysis of the conjugates,
      is likely to significantly underestimate the total concentration of alkylphenol
      residues and may not serve as an appropriate biomarker for quantifying the
      exposure of wild fish to alkylphenols.

PMID- 12188354
TI  - Water traffic control to prevent oil spills.

PMID- 12188355
TI  - Leaching and primary biodegradation of sulfonated naphthalenes and their
      formaldehyde condensates from concrete superplasticizers in groundwater affected
      by tunnel construction.
AB  - Sulfonated naphthalenes and their formaldehyde condensates (SNFC) are used as
      concrete superplasticizers fortunnel construction through aquifers.This
      paperdiscusses their primary biodegradation in groundwater affected by
      construction activities. The analyses of groundwater samples collected 5 m away
      from a construction site clearly indicated that components of the applied SNFC
      product leached into the groundwater. A maximum total concentration of these
      compounds of 233 microg/L was found, and it was shown that only the monomeric
      sulfonated naphthalenes andthe condensates uptothetetramerleached in substantial
      amounts. The decrease in concentration of several monomeric components could not
      be explained by mere dispersion but rather indicates a biological transformation
      in the aquifer. This was confirmed at a second field site and by laboratory
      degradation experiments with piezometer material as inoculum. Lag phases for the
      individually degradable sulfonated naphthalenes ranged from 0 to 96 d.
      Naphthalene-1,5-disulfonate and the oligomeric components were neither degraded
      in the aquifer nor in the laboratory experiments within an observation time of up
      to 195 d. This clearly indicates their persistence in subsurface waters.

PMID- 12188356
TI  - Dechlorination of chlorobenzenes by a culture containing bacterium DF-1, a PCB
      dechlorinating microorganism.
AB  - Polychlorinated benzenes were reductively dechlorinated by an enrichment culture
      containing the polychlorinated biphenyl (PCB) dechlorinating bacterium DF-1. The
      culture dechlorinated hexachlorobenzene (hexa-CB) --> pentachlorobenzene (penta
      CB) --> 1,2,3,5-tetrachlorobenzene (1,2,3,5-CB) --> 1,3,5-trichlorobenzene (1,3,5
      CB) and did not dechlorinate other tetrachlorobenzenes or any trichlorobenzenes.
      This restricted series of reactions is the most predominant and frequently
      reported pathway for the dechlorination of hexa-CB and penta-CB by enrichment
      cultures inoculated with either freshwater or estuarine sediments. The culture
      did not dechlorinate hydroxylated and methoxylated polychlorinated benzenes or a
      hydroxylated PCB. Bacterium DF-1 was detected by PCR/DGGE analysis following
      dechlorination of penta-CB but was not detected when a chlorinated benzene (CB)
      was not dechlorinated; detection of other members in the communitywas unaffected
      by the presence or absence of CB dechlorination. This is the first report of a
      bacterium that reductively dechlorinates both PCBs and CBs and the first
      identification of an organism that can dechlorinate a CB with more than four
      chlorines.

PMID- 12188357
TI  - Indoor hydrogen peroxide derived from ozone/d-limonene reactions.
AB  - In this pilot study, performed in an office manipulated to resemble an
      environment with a strong indoor ozone source or a significant influx of outdoor
      air during a smog event, reactions between ozone and d-limonene produced
      hydroperoxides. Hydrogen peroxide (H202) presumably constituted the majority of
      the measured hydroperoxides, although a small amount of organic hydroperoxides
      (ROOH) may have contributed to the signal. Total hydroperoxides were 1.0-1.5 ppb
      at low air exchange rates (0.5-4 h(-1)) and 0.6-0.8 ppb at high air exchange
      rates (12-18 h-1). The net estimated yield ranged from 1.5 to 3.2%, consistent
      with values reported in the literature. Based on these yields and typical indoor
      scenarios, peak indoor concentrations of H202 are projected to be comparable
      with, but not significantly larger than, peak outdoor concentrations. Hygroscopic
      secondary organic aerosols (SOA; 10-100 microg m(-3)) were simultaneously
      generated by the ozone/d-limonene reactions; their co-occurrence with H202
      provides a mechanism whereby H2O2 can be transported into the lower respiratory
      tract. The results demonstrate that reduced air exchange rates lead to increased
      concentrations of H2O2 and SOA as well as a shift in the size-distribution toward
      larger particles (0.3-0.7 microm diameter), potentially increasing the amount of
      H2O2 delivered to the lower respiratory region. This study increases our
      understanding of H2O2 exposures, including exposures to H2O2 associated with co
      occurring hygroscopic aerosols. It also re-emphasizes the potential of ozone
      driven chemistry to alter indoor environments, often producing products more
      irritating than their precursors.

PMID- 12188358
TI  - Complexation studies of Eu(III) with alumina-bound polymaleic acid: effect of
      organic polymer loading and metal ion concentration.
AB  - To contribute to the comprehension of the metal ion sorption properties in mixed
      mineral-organic matter systems, interaction studies between Eu(III) and
      polymaleic acid (PMA)-coated alumina colloids were carried out at pH 5 in 0.1 M
      NaClO4. The studied parameters were the metal ion concentration (1 x 10(-10) to 1
      x 10(-4) M) and PMA loading on alumina (gamma = 10-70 mg/g). The data were
      described by a surface complexation model. The constant capacitance model was
      used to account for electrostatic interactions. The results showed thattwo sites
      were necessary to explain the sorption data. At high Eu loading, Eu is surrounded
      by one carboxylate group and one aluminol group. The existence of this ternary
      surface site was in agreement with time-resolved laser-induced fluorescence
      spectroscopy measurements. At low metal ion concentrations, a surface site
      corresponding to a 1:1 Eu/COO-stoichiometry was deduced from modeling.
      Spectroscopic data did not corroborate the existence of this latter site. This
      discrepancy was explained by postadsorption kinetic phenomenon: a migration of
      the metal ion within the adsorbed organic layer.

PMID- 12188359
TI  - A magnetic resonance imaging study of dense nonaqueous phase liquid dissolution
      from angular porous media.
AB  - Magnetic resonance imaging (MRI) was used to determine the effects of pore-scale
      heterogeneity on the dissolution of a nonaqueous phase liquid (NAPL) in water
      saturated flow-through columns (1.2 cm in diameter) packed with either
      approximately 500 or approximately 1,000 micron diameter angular silica gel
      (referred to as SG500 and SG1000, respectively). Columns were contaminated with
      1,3,5-trifluorobenzene at residual saturation and then purged with water at a
      constant Darcy velocity of 1.83 m/day. Three-dimensional 19F images were acquired
      every 2-5 h at an imaging resolution of 59 x 234 x 234 microm3. Imaging results
      show that the specific NAPL surface area (a(t)) is linearly related to the NAPL
      volumetric fraction (theta(n)) and that the constant of proportionality between
      these parameters is determined by the blob size and geometry distribution.
      Overall (expressed as the modified Sherwood number, Sh') and intrinsic (expressed
      as the apparent Sherwood number, Sh(apt)) mass transfer rate coefficients were
      calculated. Values of Sh' and Sh(apt) for SG500 were approximately three times
      less than those for SG1000. For both solids, Sh' first increased or stayed the
      same and then decreased with decreasing theta(n), while Shapt generally increased
      with decreasing theta(n). These results suggest that during dissolution new flow
      paths were created (i.e., bypass zones were eliminated) as NAPL dissolved,
      decreasing the fraction of NAPL-water interfaces adjacent to pores filled with
      stagnant water and the average diffusion length scale. Since at for SG500 was
      dominated by less spherical multipore blobs (as opposed to more spherical
      singlets for SG1000), these results also suggest that the extent of flow
      bypassing (and the average diffusion length scale) increases in systems with more
      irregular blobs. These results are important because Sh' correlations and a
      "sphere" dissolution model do not account for transient changes in the fraction
      of NAPL surface area that contributes to dissolution or for the effect of initial
      blob size and geometry distribution on this fraction.

PMID- 12188360
TI  - Modeling digestive tract absorption and desorption of lipophilic organic
      contaminants in humans.
AB  - A model of the absorption and desorption of persistent lipophilic organic
      pollutants in the human gastrointestinal tract was formulated. The influence of
      the dietary intake of chemical, the chemical concentration in human tissue, the
      physical-chemical properties of the chemical, and the sorption properties of the
      feces on the predicted net mass transfer of chemical was explored and shown to be
      consistent with experimental observations. The model was parametrized and tested
      using a data set of approximately 800 measurements of net absorption/excretion of
      polychlorinated biphenyls, dibenzo-p-dioxins, and dibenzofurans that were
      obtained in experiments with 14 human volunteers. Overall good agreement was
      obtained between the predicted and measured values. The largest discrepancies
      were observed in cases of net excretion because the model was not able to account
      for the considerable individual and temporal variability in the sorption
      properties of the feces. In a sample model application, good agreement was found
      between concentrations of octachlorodibenzo-p-dioxin in blood measured in
      different age groups of the background population and values predicted by the
      model.

PMID- 12188361
TI  - Comparison of five in vitro digestion models to study the bioaccessibility of
      soil contaminants.
AB  - Soil ingestion can be a major exposure route for humans to many immobile soil
      contaminants. Exposure to soil contaminants can be overestimated if oral
      bioavailability is not taken into account. Several in vitro digestion models
      simulating the human gastrointestinal tract have been developed to assess
      mobilization of contaminants from soil during digestion, i.e., bioaccessibility.
      Bioaccessibility is a crucial step in controlling the oral bioavailability for
      soil contaminants. To what extent in vitro determination of bioaccessibility is
      method dependent has, until now, not been studied. This paper describes a multi
      laboratory comparison and evaluation of five in vitro digestion models. Their
      experimental design and the results of a round robin evaluation of three soils,
      each contaminated with arsenic, cadmium, and lead, are presented and discussed. A
      wide range of bioaccessibility values were found for the three soils: for As 6
      95%, 1-19%, and 10-59%; for Cd 7-92%, 5-92%, and 6-99%; and for Pb 4-91%, 1-56%,
      and 3-90%. Bioaccessibility in many cases is less than 50%, indicating that a
      reduction of bioavailability can have implications for health risk assessment.
      Although the experimental designs of the different digestion systems are
      distinct, the main differences in test results of bioaccessibility can be
      explained on the basis of the applied gastric pH. High values are typically
      observed for a simple gastric method, which measures bioaccessibility in the
      gastric compartment at low pHs of 1.5. Other methods that also apply a low
      gastric pH, and include intestinal conditions, produce lower bioaccessibility
      values. The lowest bioaccessibility values are observed for a gastrointestinal
      method which employs a high gastric pH of 4.0.

PMID- 12188362
TI  - Wet oxidation lumped kinetic model for wastewater organic burden biodegradability
      prediction.
AB  - In many cases, treatment of wastewaters requires a combination of processes that
      very often includes biological treatment. Wet oxidation (WO) in combination with
      biotreatment has been successfully used for the treatment of refractory wastes.
      Therefore, information about the biodegradability of wastewater solutes and
      particulates after wet oxidation is very important. The present work proposes a
      model that can describe the oxidation process via organic concentration
      characteristics such as chemical oxygen demand (COD), biochemical oxygen demand
      (BOD), and immediately available BOD (IA BOD) and so can allow the prediction of
      biodegradability (i.e., BOD/COD ratio). The reaction mechanism includes the
      destruction of nonbiodegradable substances bytwo pathways: oxidation to carbon
      dioxide and water and oxidation to larger biodegradable compounds with their
      further degradation to smaller ones measured via IA BOD. The destruction of small
      biodegradable compounds to end products is also included in the model. The
      experiments were performed at different temperatures (170-200 degrees C) and
      partial oxygen pressures (0.5-1.5 MPa) in a batch stainless steel high-pressure
      autoclave. The model of concentrated thermomechanical pulp circulation water was
      selected for the experiments. The proposed model correlates with the experimental
      data well and it is compared with other WO models in the literature.

PMID- 12188363
TI  - Gill filament-based EROD assay for monitoring waterborne dioxin-like pollutants
      in fish.
AB  - A sensitive, accurate, and straightforward way to determine basal and induced
      ethoxyresorufin O-deethylase (EROD) activities in gill filaments, using rainbow
      trout as model species, is described. Tip pieces of primary gill filaments were
      incubated in tissue culture plate wells containing HEPES-Cortland buffer
      supplemented with 7-ethoxyresorufin. Each well was sampled on two occasions, and
      resorufin concentrations were determined by measuring the fluorescence with a
      plate reader. EROD activity was calculated from the difference in resorufin
      concentration and the interval between the two samplings. EROD activity was found
      to be significantly induced by 6 h of exposure to waterborne beta-naphthoflavone
      (1 microM). EROD in gills was also induced by caging rainbow trout in a polluted
      river or by laboratory exposure of fish to water extracted from that river. There
      was no loss of EROD activity when gill tissue was kept in ice-cold buffer for up
      to 1 d, which promotes the use of the method for studying fish exposed in the
      wild. We propose this novel method as a way to monitor dioxin-like compounds in
      aquatic environments.

PMID- 12188364
TI  - Statistical approaches to estimating mean water quality concentrations with
      detection limits.
AB  - We review statistical methodology for estimating mean concentrations of
      potentially toxic pollutants in water, for small samples that are not normally
      distributed and often contain substantial numbers of nondetects, i.e. samples
      that are only known to be below some set of fixed thresholds. Maximum likelihood
      estimation (MLE) and regression on order statistics (ROS) are two main approaches
      that dominate the literature, with transformation bias under non-normality that
      increases with the severity of censoring being the main problem. We consider
      exact maximum likelihood estimators in conjunction with the Box-Cox
      transformation and propose the Quenouille-Tukey Jackknife as a method for bias
      reduction and variance estimation. Exact maximum likelihood estimators resulting
      from the expectation-maximization (EM) algorithm are exhibited in a simple
      heuristic form that also provides estimated values for the nondetects as
      subsidiary outputs. We show in simulationsthatthetwo main approaches perform well
      for the log-normal and gamma distributions as long as the jackknife is employed
      to reduce bias. Bias corrections to MLE used in the literature are shown to
      correct in the wrong direction under severe censoring. The jackknife is also used
      for estimating the variance of the both the MLE and ROS estimators. Robustness is
      improved by searching a class of power transformations (Box-Cox) for the best
      approximating normal distribution. We conclude that both the exact MLE and ROS
      procedures can be useful under varying experimental conditions. Limited
      simulations indicate that the ROS procedure is unbiased and has a smaller
      variance than the MLE under the log-normal distribution and is robust. The MLE
      performed better in simulations involving the gamma as the underlying
      distribution. We also compare the estimators for the mean and variance that one
      obtains from typical sets of water quality data, analyzing for copper, alumnium,
      arsenic, chromium, nickel, and lead.

PMID- 12188365
TI  - Measurement of methane oxidation in lakes: a comparison of methods.
AB  - Methane oxidation in lakes constrains the methane emissions to the atmosphere and
      simultaneously enables the transfer of methane carbon to pelagic food webs.
      Several different methods have been used to estimate methane oxidation, but these
      methods have not previously been compared. In this study, we present methane
      oxidation estimates from three different lakes during summer and winter, using
      methods based on the transformation of added 14CH4, the fractionation of natural
      methane 13C, and the mass balance modeling of concentration gradients. All
      methods yielded similar results, including similar differences between lakes and
      seasons. Average methane oxidation rates varied from 0.25 to 81 mg of C m(-2) d(
      1) and indicatethatthethree methods are comparable, although they to some extent
      take different processes into account. Critical issues as well as drawbacks and
      advantages with the used methods are thoroughly discussed. We conclude that
      methods using the stable isotope or mass balance modeling approach represent
      promising alternatives, particularly for studies focusing on ecosystem-scale
      carbon metabolism.

PMID- 12188366
TI  - Hydrogen abstraction and decomposition of bromopicrin and other trihalogenated
      disinfection byproducts by GC/MS.
AB  - Tribromonitromethane (bromopicrin), dibromochloronitromethane,
      bromodichloronitromethane, and trichloronitromethane (chloropicrin) have been
      identified as drinking water disinfection byproducts (DBPs). They are thermally
      unstable and decompose under commonly used injection port temperatures (200-250
      degrees C) during gas chromatography (GC) or GC/mass spectrometry (GC/MS)
      analysis. The major decomposition products are haloforms (such as bromoform),
      which result from the abstraction of a hydrogen atom from the solvent bythermally
      generated trihalomethyl radicals. A number of other products formed by radical
      reactions with the solvent and other radicals were also detected. The
      trihalonitromethanes also decompose in the hot GC/MS transfer line, and the mass
      spectra obtained are mixed spectra of the undecomposed parent compound and
      decomposition products. This can complicate the identification of these compounds
      by GC/MS. Trihalomethyl compounds that do not have a nitro group, such as
      tribromoacetonitrile, carbon tetrabromide, methyl tribromoacetate, and
      tribromoacetaldehyde, do not decompose or only slightly decompose in the GC
      injection port and GC/MS transfer line. The brominated trihalomethyl compounds
      studied also showed H/Br exchange by some of their fragment ions. This H/Br
      exchange also makes the identification of these compounds in drinking water more
      difficult. The extent of H/Br exchange was found to depend on the mass
      spectrometer ion source temperature, and it is proposed that the internal surface
      of the ion source is involved in this process.

PMID- 12188367
TI  - Sol-gel glass immunosorbent-based determination of s-triazines in water and soil
      samples using gas chromatography with a nitrogen phosphorus detection system.
AB  - A rapid and efficient method for the selective extraction of s-triazine
      herbicides in environmental samples was developed using an immunosorbent of
      monoclonal antiatrazine antibodies, which were encapsulated in a sol-gel glass
      matrix. The cross-reactivity of the antibody for analytes structurally related
      with atrazine enabled the simultaneous extraction of several s-triazine
      herbicides (atrazine, propazine, terbuthylazine, cyanazine, desethyl atrazine).
      After trace enrichment on the immunoextraction column, the s-triazines were
      desorbed by means of an acidic buffer (pH 2.5) and further extracted with ethyl
      acetate before being injected into the GC. Compared to liquid-liquid extraction
      and solid-phase extraction with a hydrophobic SDB-L support, the GC-NPD
      chromatograms obtained after immunoaffinity enrichment of surface water (river
      water) samples or soil extracts and analysis were free from matrix interferences.
      Nonspecific adsorption of humic acids was not observed. The method allows for the
      determination of the herbicides in linear ranges up to 1.5 microg/L with
      correlation coefficients higherthan 0.99 and relative standard deviations between
      4% and 7% (n = 5). The LODs for 50-mL water samples were in the range 0.02
      microg/L (atrazine, propazine) to 0.1 microg/L (desethyl atrazine) (S/N = 3). In
      addition to its high selectivity, the immunosorbent proved to be reusable for a
      significant number of preconcentration runs. However, the composition of samples
      may influence the lifetime of the column.

PMID- 12188368
TI  - Carbon isotopes as a tool to evaluate the origin and fate of vinyl chloride:
      laboratory experiments and modeling of isotope evolution.
AB  - Accumulation of vinyl chloride (VC) is often a main concern at sites contaminated
      with chlorinated ethenes and ethanes due to its high toxicity. Since there can be
      several possible sources of VC and ethene at such sites, assessing the origin and
      fate of VC can be complicated. Aim of this study was to evaluate carbon isotope
      fractionation associated with various anaerobic processes that lead to the
      production of VC and ethene in view of using isotopes to evaluate the origin and
      fate of these compounds in groundwater. Microcosms were constructed using
      sediments and groundwater from a contaminated site and amended with potential
      precursors for VC and ethene production. In the microcosms with dichloroethene
      isomers, sequential reductive dechlorination was observed, and isotopic
      enrichmentfactors of -19.9 +/- 1.5 per thousand for cis-1,2-dichloroethene, -30.3
      +/- 1.9 per thousand for trans-1,2-dichloroethene, and -7.3 +/- 0.4 per thousand
      for 1,1-dichloroethene were obtained. In microcosms with chlorinated ethanes, 1,2
      dichloroethane (1,2-DCA) and 1,1,2-trichloroethane (1,1,2-TCA) were predominantly
      transformed by dichloroelimination to ethene and VC, respectively, and
      enrichmentfactors of -32.1 +/- 1.1 per thousand for 1,2OCA and -2.0 +/- 0.2 per
      thousand for 1,1,2-TCA were observed. Except for 1,1,2-TCA, a strong 13C
      enrichment in each of the potential precursor of VC was observed, which opens the
      possibility to trace the origin of VC based on the isotope ratio of potential
      precursors. Furthermore, it was possible to model the isotope evolution of VC
      present as substrate or intermediate product as a function of time. The study
      demonstrates that carbon isotope ratios can potentially be used for qualitative
      and possibly quantitative evaluation of the origin and fate of VC at sites with
      complex contaminant mixtures.

PMID- 12188369
TI  - Theoretical considerations on the use of solid-phase microextraction with complex
      environmental samples.
AB  - The equations governing the use of equilibrium solid-phase microextraction (SPME)
      for environmental samples with complex heterogeneous matrices were derived in
      terms of parameters commonly measured or estimated by environmental scientists.
      Parameterization of the SPME equations allowed for the a priori prediction of
      SPME performance as a function of analyte and sample properties as well as
      experimental conditions. A theoretical evaluation of SPME was performed for a
      broad range of realistic scenarios using calculated equilibrium partitioning
      parameters and the implications for practical applications were discussed.
      Potential pitfalls and errors in quantitative measurements were identified, and
      different approaches to SPME calibration were presented. The concept of an
      optimum minimum volume for the analysis of heterogeneous environmental samples
      was presented and fully developed. Data from three previous studies were used to
      validate the correctness of our theoretical framework; the agreement between the
      measured relative recoveries of a variety of hydrophobic organic chemicals and
      theoretical predictions was reasonable. The results of this study highlight the
      potential for SPME to be a valuable technique for the measurement of hydrophobic
      organic contaminants in complex environmental samples. The SPME technique appears
      to be especially well suited for samples with high solids-to-water ratios and/or
      large sample volumes. Examples of such applications include sediment interstitial
      water and in situ field measurements, respectively.

PMID- 12188370
TI  - Varations of molecular weight estimation by HP-size exclusion chromatography with
      UVA versus online DOC detection.
AB  - High performance size exclusion chromatography (HPSEC) with ultraviolet
      absorbance (UVA) detection has been widely utilized to estimate the molecular
      weight (MW) and MW distribution of natural organic matter (NOM). However, the
      estimation of MW with UVA detection is inherently inaccurate because UVA at 254
      nm only detects limited components (mostly pi bonded molecules) of NOM, and the
      molar absorptivity of these different NOM constituents is not equal. In
      comparison, a SEC chromatogram obtained with a DOC detector showed significant
      differences compared to a corresponding UVA chromatogram, resulting in different
      MW values as well as different estimates of polydispersivity. The MWs of Suwannee
      River humic acid (SRHA), Suwannee River fulvic acid (SRFA), and various mixtures
      thereof were estimated with HPSEC coupled with UVA and DOC detectors. The results
      show that UVA is not an adequate detector for quantitative analysis of MW
      estimation but rather can be used only for limited qualitative analysis. The NOM
      in several natural waters (Irvine Ranch, California groundwater, and Barr Lake,
      Colorado surface water) were also characterized to demonstrate the different MWs
      obtained with the two detectors. The results of the SEC-DOC chromatograms
      revealed NOM constituent peaks that went undetected by UVA. Utilizing online DOC
      detection, a better representation of NOM MWs was suggested, with NOM displaying
      higher weight-averaged MW (Mw) and lower number-averaged MW (Mn) as well as
      higher polydispersivity. A method for estimation of the MWs of NOM fractional
      components and polydispersivities is presented.

PMID- 12188371
TI  - Comparison between donor substrates for biologically enhanced tetrachloroethene
      DNAPL dissolution.
AB  - Tetrachloroethene (PCE) dense nonaqueous-phase liquid (DNAPL) can act as a
      persistent groundwater contamination source for decades. Biologically enhanced
      dissolution of pure PCE DNAPL has potential for reducing DNAPL longevity as
      indicated previously (Environ. Sci. Technol. 2000, 34, 2979). Reported here are
      expanded studies to evaluate donor substrates that offer different remediation
      strategies for bioenhanced DNAPL dissolution, including pentanol (soluble
      substrate, fed continuously), calcium oleate (insoluble substrate, placed in
      column initially by alternate pumping of sodium oleate and calcium chloride), and
      olive oil (mixed with PCE and placed in column initially). Compared with a no
      substrate column control, the DNAPL dissolution rate was enhanced about three
      times when directly coupled with biological transformation. The major degradation
      product formed was cDCE, but significant amounts of VC and ethene were also found
      with some columns. Extensive methanogenesis, which reduced PCE transformation,
      occurred in both the pentanol-fed and oleate-amended columns, but not in the
      olive-oil-amended column, suggesting that methanogens managed to colonize column
      niches where PCE DNAPL was not present. Detrimental methane production in the
      pentanol-fed column was nearly eliminated by presaturating the feed solution with
      PCE. These results suggest potential DNAPL remediation strategies to enhance
      dehalogenation while controlling competitive methanogenic utilization of donor
      substrates.

PMID- 12188372
TI  - Arsenic adsorption by Fe(III)-loaded open-celled cellulose sponge. Thermodynamic
      and selectivity aspects.
AB  - Nowadays there is a great concern on the study of new adsorbent materials for
      either the removal or fixation of arsenic species because of their high toxicity
      and the health problems associated to such substances. The present paper reports
      a basic study of the adsorption of arsenic inorganic species from aqueous
      solutions using an open-celled cellulose sponge with anion-exchange and chelating
      properties (Forager Sponge). Consequences of preloading the adsorbentwith Fe(III)
      to enhance the adsorption selectivity are discussed and compared with the
      nonloaded adsorbent properties. The interactions of arsenic species with the
      Fe(III)-loaded adsorbent are accurately determined to clarify the feasibility of
      an effective remediation of contaminated waters. Arsenate is effectively adsorbed
      by the nonloaded and the Fe(III)-loaded sponge in the pH range 2-9 (maximum at pH
      7), whereas arsenite is only slightly adsorbed by the Fe(III)-loaded sponge in
      the pH range 5-10 (maximum at pH 9), being that the nonloaded sponge is unable to
      adsorb As(III). The maximum sorption capacities are 1.83 mmol As(V)/g (pH
      approximately 4.5) and 0.24 mmol As(lII)/g (pH approximately 9.0) for the Fe(III)
      loaded adsorbent. This difference is explained in terms of the different acidic
      behavior of both arsenic species. The interaction of the arsenic species with the
      Fe(III) loaded in the sponge is satisfactorily modeled. A 1:1 Fe:As complex is
      found to be formed for both species. H2AsO4- and H3AsO3 are determined to be
      adsorbed on Fe(III) with a thermodynamic affinity defined by log K = 2.5 +/- 0.3
      and log K = 0.53 +/- 0.07, respectively. As(V) is, thus, found to be more
      strongly adsorbed than As(III) on the Fe(III) loaded in the sponge. A significant
      enhancement on As(V) adsorption selectivity by loading Fe(III) in the sponge is
      observed, and the effectiveness of the Fe(III)-loaded sponge for the As(V)
      adsorption is demonstrated, even in the presence of high concentrations of
      interfering anions (chloride, nitrate, sulfate, and phosphate).

PMID- 12188373
TI  - Photocatalytic oxidation of bacteria, bacterial and fungal spores, and model
      biofilm components to carbon dioxide on titanium dioxide-coated surfaces.
AB  - We report carbon mass balance and kinetic data for the total oxidation of cells,
      spores, and biomolecules deposited on illuminated titanium dioxide surfaces in
      contact with air. Carbon dioxide formation by photocatalytic oxidation of
      methanol, glucose, Escherichia coli, Micrococcus luteus, Bacillus subtilis (cells
      and spores), Aspergillus niger spores, phosphatidylethanolamine, bovine serum
      albumin, and gum xanthan was determined as a function of time. The quantitative
      data provide mass balance and rate information for removal of these materials
      from a photocatalytic surface. This kind of information is importantfor
      applications of photocatalytic chemistry in air and water purification and
      disinfection, self-cleaning surfaces, and the development of self-cleaning air
      filters.

PMID- 12188374
TI  - Potential method for reducing emissions of polycyclic aromatic hydrocarbons from
      the incineration of biological sludge for the terephthalic acid manufacturing
      industry.
AB  - This study illustrates a potential method for reducing PAH emissions from the
      incineration of biological sludge by adding a suitable and available waste as a
      co-fuel. The whole study was conducted on a full-scale fluidized-bed incinerator
      operated by a terephthalic acid (TPA) manufacturing plant for disposing of
      biological sludge. Two incinerating conditions were studied, one directly
      incinerating biological sludge (the normal incinerating condition), and the other
      adding the waste TPA as a co-fuel during the biological sludge incineration
      process (the trial incinerating condition). Both incinerating conditions used
      heavy oil as auxiliary fuel. Although the former had a higher heavy oil
      consumption rate than the latter, both had comparable combustion efficiencies.
      Results show that the total PAH input mass rate for the former was only 2.35
      times higher than the latter, but the total PAH emission factor for the former
      was 6.52 times higher than the latter. Total PAH output/input mass ratios for
      both incinerating conditions were lower than unity, but the value for the normal
      incinerating condition was approximately 2.91 times higher than the trial
      condition. In conclusion, the use of waste TPA as a co-fuel not only saved the
      consumption of heavy oil but also reduced PAH emissions during the combustion
      process.

PMID- 12188375
TI  - Pesticide adsorption by granular activated carbon adsorbers. 1. Effect of natural
      organic matter preloading on removal rates and model simplification.
AB  - The adsorptive removal of periodic spikes of the trace synthetic organic
      chemicals (SOCs) simazine and asulam from water containing natural organic matter
      (NOM) was studied in pilot-scale granular activated carbon (GAC) adsorbers over a
      period of nearly 3 years. The SOC removal percentage obtained at any preloading
      time and bed depth was independent of the liquid-phase SOC concentration, and
      equations derived from the ideal adsorbed solution theory and a pore surface
      diffusion model validated this observation. The pseudo-steady-state SOC removal
      rate, (dC/dz), at each preloading time and bed depth was therefore first order
      with respectto the liquid-phase SOC concentration, C. Furthermore, the removal
      modulus, k, in the resulting SOC removal rate expression was a reflection of the
      solid-phase concentration of the NOM fraction that interfered with the adsorption
      of SOCs. Analysis of the removal modulus values indicated that the mass transfer
      zone of the NOM fraction competing with asulamtraveled more rapidlythrough the
      GAC adsorber than that competing with simazine. Given the similar molecular sizes
      of the targeted SOCs, this result was primarily explained by differences in SOC
      adsorbabilities, where the more weakly adsorbing asulam was less capable of
      displacing preloaded NOM. Consequently, the NOM fraction competing with asulam
      constituted a larger percentage of the total NOM than that competing with
      simazine.

PMID- 12188376
TI  - Pesticide adsorption by granular activated carbon adsorbers. 2. Effects of
      pesticide and natural organic matter characteristics on pesticide breakthrough
      curves.
AB  - The principal objective of this study was to elucidate mechanisms by which NOM
      affects the adsorption of a nonpolar (simazine) and a polar (asulam) herbicide on
      activated carbon. Experiments were carried out in microcolumns that were
      continuously fed solutions containing NOM with different molecular weight (MW)
      distributions and intermittently solutions containing the same NOM plus simazine
      or asulam. The MW distributions of a groundwater NOM were altered by coagulation
      and ultrafiltration, which resulted in the preferential removal of high-MW, UV260
      absorbing NOM. At a given NOM loading, the simazine removal efficiency was higher
      in the column that was preloaded with raw groundwater than in columns receiving
      coagulated or ultrafiltered water. In contrast, the asulam removal efficiency was
      similar for all three NOM solutions at a given NOM loading. Therefore, the
      results suggested that low-MW, UV260-absorbing NOM molecules competed directly
      with strongly adsorbing pesticides, such as simazine, for adsorption sites. For
      more weakly adsorbing pesticides, such as asulam, direct competition for
      adsorption sites originated not only from the strongly adsorbing, low-MW NOM, but
      also from more weakly adsorbing, higher-MW NOM. Consequently, the competing NOM
      fraction increases as the adsorbability of the SOC decreases, a result that was
      confirmed by adsorption data for additional pesticides of similar size. However,
      a smaller pesticide competed more effectively for adsorption sites than a larger
      pesticide of similar polarity, suggesting that the concentration of competing NOM
      decreases as the MW of the SOC decreases.

PMID- 12188377
TI  - Use of polymer mats in series for sequential reactive barrier remediation of
      ammonium-contaminated groundwater: laboratory column evaluation.
AB  - Large-scale column experiments were undertaken to evaluate the potential of in
      situ polymer mats (installed in series) to be used as permeable reactive barriers
      for delivery of oxidants and reductants to induce sequential bioremediation of
      ammonium-contaminated groundwater (approximately 120mg L(-1) NH4+-N), without
      bioaugmentation. The strategy was for the first group of polymer mats to deliver
      oxygen to induce bacterial nitrification of the ammonium to nitrite/ nitrate as
      the groundwater moved past and for the second group of polymer mats to deliver
      hydrogen or ethanol, to induce bacterial denitrification of the nitrite/nitrate
      to produce nitrogen gas. Once purging of the first polymer mat commenced,
      ammonium concentrations decreased downgradient from the polymer mats.
      Nitrification rates increased and stabilized over the 6-month experiment, with
      stable nitrification half-lives in the range 0.07-0.25 days. Nitrification most
      likely occurred in a biologically active zone at the polymer wall/aqueous
      interface. With hydrogen delivery via the polymer mats, a denitrification half
      life (nitrate plus nitrite removal) of 3.5 days was induced. Denitrification
      rates were significantly enhanced when ethanol was delivered via a polymer mat,
      with denitrification half-lives in the range of 0.12-0.34 days. Nitrification/
      denitrification rates were maintained for groundwater flow rates up to 300 m yr(
      1), suggesting oxygen and ethanol delivery rates via the polymer mats were
      sufficient not to limit nitrification or denitrification. In soil columns, the
      polymer mat delivery system provided an effective and reliable technique for
      delivery of oxygen and hydrogen or ethanol for sequential
      nitrification/denitrification of ammonium-contaminated groundwater. Scale-up of
      this concept to a field pilot-scale is currently underway.

PMID- 12188378
TI  - Utilizing renewable resources to create functional polymers: chitosan-based
      associative thickener.
AB  - There is a growing interest in utilizing renewable resources and exploiting
      biological reactions for environmentally friendly products and processes. We
      report the use of the enzyme tyrosinase to graft the natural phenol, catechin,
      onto the biopolymer chitosan. Chemical evidence for grafting was obtained by
      UV/visible spectrophotometry and electrospray mass spectrometry. Rheological
      measurements demonstrate that the catechin-modified chitosan behaves as an
      associative thickener. Specifically, the viscosity increases dramatically with
      concentration of this modified chitosan. Furthermore, when the catechin-modified
      chitosan is dissolved at low concentrations (0.6% w/w), steady shear measurements
      show shear thinning behavior, while oscillatory measurements show weak gel
      behavior. These results demonstrate the potential for utilizing renewable
      resources and biochemical processing to functionalize biopolymersto
      offertechnically useful properties. To suggest the relative environmental impacts
      of chitosan derivatives with existing water-soluble polymers, we used the
      framework of a life cycle assessment.

PMID- 12188379
TI  - Comment on "Getting serious about sustainability".

PMID- 12188380
TI  - Ear diseases and hearing in the Thai elderly population. Part I. A comparative
      study of the accuracy of diagnosis and treatment by general practitioners vs ENT
      specialists.
AB  - The prevalence of ear disease and hearing disability in elderly Thais in 14 urban
      communities around Siriraj Hospital was studied. The accuracy of diagnosis and
      treatment of common ear diseases and of screening for hearing loss in the elderly
      between general practitioners (GP) and Ear, Nose and Throat (ENT) specialists was
      also compared. Elderly people aged 60 years or more who had registered with the
      health care program had their ear and hearing check-up performed by GPs and ENT
      specialists from mobile team. Altogether, 980 subjects were included, 332 were
      males, 648 were females, (male:female ratio 1:2). Their ages ranged from 60-96
      years with an average age of 68.5 years. The prevalence of ear disease diagnosed
      by ENT specialists was 16.3 per cent (95% CI = 14.0-18.6), 12.5 per cent was
      external ear disease and 2.7 per cent middle ear disease. The most common ear
      problem was impacted ear wax (8%), the second most common problem was otitis
      externa (4.3%). Compared with an ENT specialist, the ability of a GP to diagnose
      ear diseases had a sensitivity of 46.5 per cent and a specificity of 80.3 per
      cent, the positive predictive value of their diagnoses was 31.5 per cent. The
      efficacy of the treatment of ear diseases in 51 elderly people by GPs and in 63
      elderly people by ENT specialists was statistically significantly different (p =
      0.02). Hearing screening by the GP using whisper or the watch test performed in
      650 elderly people revealed abnormal findings (could not hear) in 70 cases or
      10.8 per cent. Hearing screening using pure tone audiometry in 980 elderly people
      showed abnormal hearing level in 508 cases (52.4%). 9.5 per cent of them had a
      bilateral moderate to severe degree of hearing impairment. There was no
      difference in the level of hearing impairment between males and females or
      between right and left ears. The prevalence of hearing loss increases with
      increasing age. Tympanometry performed by an acoustic impedance machine in 980 of
      the elderly showed a conductive hearing loss in 85 cases (9.1%). The authors
      conclude that the prevalence of ear disease in elderly people living in the urban
      community around Siriraj Hospital is quite high. Although the ear diseases
      commonly encountered were not serious, if left untreated they may lead to
      complication and decreased hearing. Therefore, the proficiency of GPs in the
      management of common ear diseases in every community should be regularly
      maintained. Hearing impairment is very prevalent and increases with age. Thus,
      screening for hearing loss using an audiometer and/or acoustic impedance is
      recommended for all senior citizens in their community at least once a year.
      Early detection of elderly persons who could benefit from a properly fitted
      hearing aid will certainly improve the quality of life and may prevent
      psychiatric and functional impairment of the Thai elderly population.

PMID- 12188381
TI  - Ear diseases and hearing in the Thai elderly population. part II. A one year
      follow-up study.
AB  - The ear and hearing survey of the Thai elderly in 14 urban communities around
      Siriraj Hospital was repeated one year after the first survey in order to detect
      any changes. Altogether 556 elderly people came for follow-up examination, 191
      were males, 365 were females, the average age was 68.2 years (60-88 years). Ear
      disease was diagnosed by ENT specialists in 80 cases which implied that the
      prevalence of ear disease was 14.4 per cent. This was not statistically
      significantly different from the prevalence of ear disease in the survey
      conducted in the previous year and although the elderly who had ear diseases in
      the first survey had already been treated, the prevalence did not decrease. Some
      elderly people only had ear diseases in this survey. Hearing evaluation by pure
      tone audiometry was performed in 549 elders. There were 12.4 per cent who had
      bilateral, moderate to severe hearing loss which was 2.9 per cent higher than in
      the previous survey. The hearing level had also deteriorated in 14.3 per cent of
      the elderly people. Tympanometry was performed in 556 cases and showed that 10.5
      per cent had a conductive hearing loss. When audiometry and tympanometry of the
      same elderly people were evaluated together, 49.2 per cent of them had a
      sensorineural hearing loss, 3 per cent had a conductive hearing loss and 6.5 per
      cent had a conductive or mixed type hearing loss. When the results of audiometry
      were compared with the self identification/perception of their hearing reported
      by the elderly in the questionnaires, they were not reliable. In conclusion, a
      one-year follow-up study of the prevalence of ear disease and hearing impairment
      in the elderly showed that the prevalence of ear disease was still high and had
      not changed significantly. Concerning hearing impairment, not only had the
      prevalence increased, but also the severity of hearing loss. Therefore, the
      authors stress the need to implement the "Ear and Hearing Care" program for the
      elderly both in rural and urban communities at least once a year in order to
      improve quality of life of the elderly Thai people and to prevent complications
      of ear disease.

PMID- 12188382
TI  - Prevalence and incidence of depression in the Thai elderly.
AB  - The purposes of this study were to study the prevalence and incidence of
      depression in elderly Thais. A field survey study was implemented. The sample
      consisted of 1,713 elderly people in 35 communities from 4 districts surrounding
      Siriraj Hospital Bangkok Noi, Bangkok Yai, Taling Chun and Bang Plud. These areas
      are the peripheral part of Bangkok and most of them have extended family. The
      Thai Geriatric Depression Scale (TGDS) and the Thai Mini Mental State Examination
      (TMSE) were used as screening tests, for data collection. The prevalence of
      depression was 12.78 per cent, of which 8.23 per cent had only depressive
      symptomatology (male 5.43%, female 9.63%) while 4.55 per cent had both depression
      and cognitive impairment (male 2.8%, female 5.54%). The point incidence (one
      year) of depression was 7.27 (male 1.58%, female 5.68%). The major contributing
      factors in depression were financial, poor family relationships and physical
      illness. The prevention and management of these factors may bring about a better
      quality of life for the elderly in Thailand.

PMID- 12188383
TI  - Research on development of the manual for self detection of depression in the
      Thai elderly.
AB  - The purposes of this study were to develop an effective manual for the early self
      detection of depression in the Thai elderly, to detect the comorbidity of
      depression (pattern of drug and alcohol abuse, suicidal idea) and to ascertain
      the quality of life. A quasi experimental field research methodology (Randomized
      Control Group Pretest-Posttest Design) was implemented. The sample consisted of
      1,390 elderly people in 35 communities from 4 districts surrounding Siriraj
      Hospital-Bangkok Noi, Bangkok Yai, Taling Chan and Bang Phlat. These areas are
      the peripheral parts of Bangkok and most of them have extended families. The
      result showed that: 1. The internal consistency reliability of the nine criteria
      of the manual for the self detection of depression in the Thai elderly ranged
      from 0.84 to 0.94. The validity tested by epidemiological methods, disclosed that
      the sensitivity was 82.14 per cent and the specificity was 97.56 per cent. 2.
      There was a statistically significant difference in the incidence of depression
      between the study and the control group (p<0.000); self referred cases = 86.7 per
      cent and 9.8 per cent respectively. The study group was able to detect depression
      in 42 days, while the control group did so in 122 days. In addition, in the
      associated comorbidity, there were differences in the patterns of drug and
      alcohol abuse, suicidal ideas and quality of life after the experiment. These
      findings showed a decreasing pattern of self medication for depression, and
      suicidal ideas and an improvement in the quality of life in the study group.

PMID- 12188384
TI  - Epstein-barr virus-associated non-Hodgkin's lymphoma of B-cell origin, Hodgkin's
      disease, acute leukemia, and systemic lupus erythematosus: a serologic and
      molecular analysis.
AB  - Parallel studies of (a) patients with Epstein-Barr virus (EBV)-associated
      peripheral T-cell proliferative disease/lymphomas and (b) a group of patients
      with a prolonged fever from other causes were conducted at Songklanagarind
      University Hospital from 1997 through 2000. (Reports on EBV-associated peripheral
      T-cell and NK-cell proliferative disease/lymphomas have been published elsewhere)
      In this study, the authors identified 58 patients; 14 were non-Hodgkin's lymphoma
      of B-cell origin (NHL-B), 8 were Hodgkin's disease, 6 were acute leukemia, 9 were
      systemic lupus erythematosus (SLE), and 21 were patients with other diseases.
      Serologic tests for the EBV infection, the study of EBV genome in circulating non
      T-cells (CD3-cells) and T-cells (CD3+ cells), and the EBV-RNA study in the tumor
      cells were performed. EBV internal repeat-1 region (IR-1) in peripheral blood
      CD3+ cells was detected in 10 of 14 patients (71.5%) with NHL-B, 3 of 8 patients
      (37.5%) with Hodgkin's disease, 1 of 6 patients (16.7%) with acute leukemia, 4 of
      9 patients (44.5%) with SLE, and was not detected in any of the 21 patients with
      other diseases. Anti-viral capsid antigen-IgG was significantly elevated in
      hematologic malignancy patients with EBV IR-1 genome in the peripheral blood CD3+
      cells when compared to hematologic malignancy patients with a negative result,
      whereas there was no significant difference in anti-EBV nuclear antigen among
      these two groups. EBV-RNA expression in tumor cells by in situ hybridization was
      detected in 4 of 13 patients (31%) with NHL-B (all showed EBV IR-1 genome in
      peripheral blood CD3+ cells), and 3 of 5 patients (60%) with Hodgkin's disease
      (only two showed EBV IR-1 genome in peripheral blood CD3+ cells). These data
      support the theory that chronic EBV infection is often found in association with
      cases of NHL-B, Hodgkin's disease, acute leukemia, and SLE.

PMID- 12188385
TI  - Correlation of histological subtypes of basal cell carcinoma with age, sex and
      distribution of skin lesions: a five-year study at Ramathibodi Hospital.
AB  - Records and histopathology of skin lesions of patients with basal cell carcinoma
      (BCC) who attended the skin clinic at Ramathibodi Hospital from 1993 to 1997 were
      reviewed to find the correlation of histological subtypes with age, sex and
      distribution on the body of BCC. It was found that superficial BCC was
      significantly more common on the trunk, while other types were significantly more
      common on the head and neck. The mean age and sex of the patients with
      superficial BCC were not different from those other subtypes. It was concluded
      that superficial BCC tended to be more common on the trunk while other types were
      more common on the head and neck. The pathogenesis of superficial BCC may be
      different from other types of BCC.

PMID- 12188386
TI  - Incidence of hip fracture in Chiang Mai.
AB  - The reported incidence of hip fracture varies to a large extent across regions.
      Most studies relied on hospital data under the assumption that nearly all cases
      of hip fracture get access to hospital care. As in many developing countries, a
      number of hip fracture cases in Thailand might not seek care in hospitals due to
      geographical, socio-cultural and financial barriers. Therefore, using hospital
      data alone, could lead to under estimation of the magnitude of hip fracture. This
      study was undertaken to obtain such information using a combined method of
      hospital discharge survey and a cross sectional community survey. It resulted in
      an estimated incidence of 151.2 per 100,000 (95% CI 136.7-167.2) from the
      hospital survey and 185.2 per 100,000 (95% CI 138.1-247.6) from the community
      survey. In comparison to developed countries, age-adjusted incidence of hip
      fracture in this study was markedly lower than that reported from developed
      countries. It was argued that different degree of urbanization might explain the
      discrepancy. This implicated promotion of physical activity as a public health
      measure to prevent hip fracture.

PMID- 12188387
TI  - Surgical wound infection post surgery in perforated appendicitis in children.
AB  - OBJECTIVE: To compare the rate of wound infection of perforated appendicitis in
      children between primary wound closure and delayed primary wound closure. STUDY
      DESIGN: Prospective clinical trial. MATERIAL AND METHOD: Children diagnosed with
      perforated appendicitis between January 1999 and December 1999 received
      gentamicin and metronidazole pre- and post-operatively. Intra-abdominal fluid
      cultured and tested for sensitivity. The rate of wound infection, skin closure
      for patients were compared between primary wound closure and delayed primary
      wound closure. RESULTS: Among 198 children diagnosed with appendicitis, 44 cases
      were perforated (22.22%). Of these 44 cases, 8 cases had wound infection
      (18.18%), 2 of 8 Infected cases (9.1%) were in the primary wound closure group, 6
      of 8 (27.3%) were in the delayed primary wound closure group. CONCLUSION: The
      rate of wound infection from perforated appendicitis in children is still high.
      Primary wound closure has a significantly lower rate of wound infection compared
      with delayed primary wound closure.

PMID- 12188388
TI  - Hb G Makassar (beta 6:Glu-Ala) in a Thai family.
AB  - Hemoglobin G Makassar was identified in a family of Thai origin, which was found
      to share identical properties with hemoglobin S in routine hemoglobin separation
      both by cellulose acetate electrophoresis and cation-exchange HPLC. It is,
      therefore, subjects with hemoglobin G Makassar and hemoglobin S who may sometimes
      be mistakenly identified for each other. In this study, identification of
      hemoglobin G Makassar was achieved by DNA sequence analysis, which revealed a
      single nucleotide substitution GAG-->GCG at codon 6 of the beta-globin gene. The
      hemoglobin variant was hemoglobin G Makassar [beta 6:Glu-->Ala]. This is the
      first report of hemoglobin G Makassar in Thailand.

PMID- 12188389
TI  - Risk of breast cancer in post-menopausal women using hormone replacement therapy.
AB  - OBJECTIVE: To study the relationship of hormone replacement therapy (HRT) in post
      menopausal women and risk of breast cancer. PATIENTS AND METHOD: The authors
      conducted a case-control study comparing the proportion of HRT used between
      breast cancer and non-breast-cancer women. Cases were breast cancer patients who
      had natural menopause (excluded hysterectomy) and aged > or = 50-years-old from
      the Siriraj Breast Cancer database (1983-1996). Controls were post-menopausal
      volunteers aged 50 year or older who visited Siriraj Hospital for other purposes
      such as elderly clinics, health check, etc. After informed consent, well-trained
      surgeons examined the women in the control group to exclude any potential breast
      cancer. Patient characteristics and risk factors were collected. RESULTS: Of
      1,913 patients in the database, 623 were included as the cases. Data from 679
      volunteers were collected for controls from May to December 1999. Among 1,302 of
      the study population 58 women had ever used HRT (4.5%), which distributed to 3.2
      per cent (20/623) in cases and 5.6 per cent (38/679) in controls. From univariate
      analysis, age, age at menopause, number of children, habitat, education,
      contraceptive pills, familial history of breast cancer and HRT usage were
      associated with breast cancer (p-value<0.05). After multivariate forward stepwise
      logistic regression analysis, there was no association between HRT use and breast
      cancer (adjusted odds ratio (OR) = 0.61, 95% CI = 0.31-1.20). In subgroups
      analysis, women who had older age, higher education level, history of taking
      contraceptive pills, or positive familial history of breast cancer in second
      degree relatives had a decreased risk of breast cancer, while those living
      outside Bangkok had an increased risk. CONCLUSION: Hormonal replacement therapy
      in post-menopausal women was not associated with increased risk of breast cancer.

PMID- 12188390
TI  - A randomized, open-label, comparative trial of BID and TID dosing of saquinavir
      enhanced oral formulation as part of a triple therapy for advanced AIDS patients.
AB  - OBJECTIVE: To compare the efficacy and safety of 1,400 mg BID and 1,200 mg TID of
      saquinavir soft gel given with zidovudine and lamivudine in antiretroviral-naive,
      advanced AIDS patients. METHOD: A randomized, open-label study conducted at a
      university hospital. RESULTS: Forty cases were enrolled in the study, 20 cases in
      each group. The mean CD4 cell count was 29 cells/mm3. The mean log10 HIV-1 RNA
      was 5.27 copies/mL. Using an on-treatment analysis, the reduction in plasma
      log10HIV-1 RNA of BID and TID groups was not statistically significant at -2.44
      vs -2.60 copies/mL (-0.16, 95% CI -0.63 to 0.30; p= 0.48). The mean increase in
      CD4 cell counts was not statistically significant at +144 and +159 cells/mm3 (11,
      95% CI -75 to 97; p=0.79). CONCLUSION: The preliminary data suggests that in
      antiretroviral-naive, advanced AIDS patients, 1,400 mg BID of saquinavir soft gel
      given with two nucleoside analogues might be as effective as the standard 1,200
      mg TID.

PMID- 12188392
TI  - Screening for microalbuminuria in type 2 diabetes: a reconsideration.
AB  - To study the effect of timing of urine collection in determination of
      microalbuminuria in type 2 diabetic patients, timed urine (night time and
      daytime) as well as spot urine (first morning and random morning) samples were
      collected from 44 type 2 diabetic patients, 21 with normoalbuminuria and 23 with
      microalbuminuria. The methods of spot urine albumin expression for
      microalbuminuria were also compared between albumin concentration (AC) and
      albumin to creatinine ratio (ACR). Night time albumin excretion rate (AER) was 16
      per cent lower and daytime AER was 13 per cent higher than 24-h AER (p<0.001).
      Forty-one (93%) of both night time and daytime urine samples had results
      corresponding with 24-h AER. For the spot urine, expression as AC showed a
      slightly stronger correlation with 24-h AER than expression as ACR. The levels of
      albumin in random morning urine samples were 50 and 35 per cent significantly
      higher than those in first morning urine samples when expressed as AC and ACR,
      respectively. In conclusion, because of low diurnal variation of AER, either
      daytime or night time urine could be used for screening of microalbuminuria in
      type 2 diabetes. Since mean albumin levels obtained from random morning urine
      were higher than those obtained from first morning urine, the cut-off level
      should be set higher in random morning urine in order to give comparable
      sensitivity in predicting microalbuminuria. The spot urine, either first morning
      or random morning urine, had a good correlation with the 24-h AER whether
      expressed as AC or ACR. Given the cost of the latter, the authors suggested
      measuring spot urine AC instead of ACR for screening of microalbuminuria in type
      2 diabetes.

PMID- 12188391
TI  - A prospective randomized trial of megadose methylprednisolone and high dose
      dexamethasone for traumatic optic neuropathy.
AB  - PURPOSE: To determine whether the improvement in visual acuity obtained when
      using high dose dexamethasone in the treatment of traumatic optic neuropathy was
      comparable to that of megadose methylprednisolone. METHOD: A total of forty-four
      patients with traumatic optic neuropathy were prospectively randomized and
      selected to receive intravenous high dose dexamethasone or megadose
      methylprednisolone within 2 weeks of injury. Age, gender, cause of injury,
      interval from injury to treatment, initial, post-pulse, and final visual acuity
      were analysed statistically to compare the dexamethasone and methylprednisolone
      groups. RESULTS: The mean interval to treatment was not significantly different
      (p=0.28) for the dexamethasone group at 5.5 days compared to the
      methylprednisolone group at 4.1 days. Visual improvement of at least two lines of
      the Snellen chart or two levels of unmeasured visual acuity was shown in 9
      patients (37.5%) of the dexamethasone group and 10 patients (50%) of the
      methylprednisolone group. There was no statistically significant difference
      between the initial and post-pulse visual acuity (p=1.0) and the initial and
      final visual outcome (p=0.60) in the dexamethasone group compared with the
      methylprednisolone group. CONCLUSION: There was no significant difference in the
      visual acuity obtained after treatment with intravenous dexamethasone or
      methylprednisolone for traumatic optic neuropathy.

PMID- 12188393
TI  - Day 3 serum inhibin B level of poor and good ovarian responders in the IVF
      program.
AB  - The aim of this study was to compare day-3 serum inhibin B levels of poor and
      good ovarian responders in the IVF-program. The study group consisted of 20 poor
      ovarian responders. The control group composed of 40 good ovarian responders who
      had similar demographic characteristics. The serum inhibin B levels were analysed
      by two-site-immunosorbent assay or sandwich ELISA (Enzyme Linked ImmunoSorbent
      Assay). The mean inhibin B level of the study group was 113.18 +/- 57.96 picogram
      per millilitre and of the control group was 94.05 +/- 61.81 picogram per
      millilitre. There was no statistically significant difference. The results might
      be useful as base-line data for further study.

PMID- 12188394
TI  - Normal value of bone mineral density of lumbar spine, proximal femur, and distal
      forearm of women in different age groups.
AB  - The cross sectional, descriptive study was conducted to find the reference data
      for bone mineral density (BMD) in normal women in the area around Thammasat
      University Hospital. The study population consisted of 806 women aged 15-80
      years. BMD of different parts of the body were measured by dual energy photon
      absorptiometer. The results showed that mean (+/- SD) BMD of the lumbar spine 2,
      3, 4, neck of femur, Ward's triangle of femur, greater trochanter of femur,
      ultradistal part of radius, and distal ulnar averaged from all age groups were
      0.954 +/- 0.144, 1.027 +/- 0.151, 1.059 +/- 0.147, 0.898 +/- 0.114, 0.774 +/-
      0.165, 0.777 +/- 0.103, 0.412 +/- 0.073, and 0.585 +/- 0.096 g/cm2 respectively.
      Overall, the peak BMD was between the age of 40-44 years old. It started
      decreasing from the age of 45 and decreased remarkably after the age of 50. The
      data is shown to be a database for our hospital's health policy, but the authors
      believe that it could also be used as reference data for future studies in
      Thailand. It is suggested that normal values in different areas should be
      available in the future in order to provide more specific and better health care
      according to demographic variation.

PMID- 12188396
TI  - AIDS-related primary central nervous system lymphoma: prolonged remission
      associated with highly active antiretroviral therapy.
AB  - A 36-year-old HIV-seropositive man developed progressive confusion and unilateral
      tremor of the hand. His medical history included cryptococcal meningitis and CMV
      colitis. CT scan revealed a single hyperdense mass with minimal peripheral
      enhancement at the region of the cerebral peduncle and pons, causing obstructive
      hydrocephalus. He was treated with ventriculo-peritoneal shunt and cranial
      radiotherapy. He also received treatment with highly active antiretroviral
      therapy (HAART). A CD4+ cell count was increased from 2 to 345 cells/mm3. He
      returned to normal function for about 32 months after treatment.

PMID- 12188395
TI  - PCR detection and prevalence of enterotoxin (cpe) gene in Clostridium perfringens
      isolated from diarrhea patients.
AB  - Clostridium perfringens isolated from patients with diarrhea (n=233) were
      analysed by a duplex PCR assay, in order to determine the prevalence of
      enterotoxin (cpe) gene and various factors involved in patients with cpe-positive
      isolates. This duplex PCR uses two sets of primers which amplify in the same
      reaction two different gene fragments: the phospholipase C (plc, alpha-toxin) and
      the enterotoxin (cpe) genes in C. perfringens. PCR analysis of 477 colonies of
      fecal spore isolates, from 159 patients who had a spore count > or = 10(3) cfu/g,
      gave positive plc gene detection in 436 colonies. The results were consistent
      with those obtained by using the standard method of C. perfringens species
      identification. 21 of 436 colonies gave positive results for both plc and cpe
      genes, indicating a prevalence of 4.8 per cent of C. perfringens that carried the
      cpe gene in cases of diarrhea. The majority of cases with cpe-positive isolates
      were women over 50 years of age (71.4%). These patients had diarrhea more than 6
      times per day (71.4%) with a duration of 1-3 days (100%). Furthermore, 85.7 per
      cent of cases developed diarrhea after food consumption, 28.6 per cent had high
      spore counts of more than 106/g in their feces, and 71.4 per cent were co
      infected with other enteric pathogens. The spore count should be interpreted with
      caution because not all isolates of C. perfringens from diarrhea patients with
      high fecal spore count carried the cpe gene, which encodes a sporulation
      associated enterotoxin. CONCLUSION: The duplex PCR assay can thus become a tool
      for C. perfringens species identification together with the detection of
      enterotoxin gene. This PCR assay is faster, less expensive and more suitable for
      large-scale use in epidemiological studies than conventional procedures. The
      authors recommend this assay to screen for enterotoxigenic C. perfringens
      isolates from primary fecal spore isolation cultures, particularly in elderly
      patients with food-borne diarrhea and non-food related diarrhea.

PMID- 12188398
TI  - Climacteric: concept, consequence and care.
AB  - Climacteric is the period of life starting from the decline in ovarian activity
      until after the end of ovarian function. According to the definition, the period
      includes peri-menopause, menopause and post-menopause. Climacteric is considered
      to be a natural change of life which may be accompanied by various health
      consequences i.e., menopausal symptoms, osteoporosis, coronary heart disease, or
      Alzheimer's disease. The key concept is that women enter menopause with different
      menopausal status for instances, natural menopause, surgical menopause, early
      menopause or even premature ovarian failure. Women may experience various health
      consequences due to the difference in genetic and environmental interaction. The
      prevalence and incidence of menopausal problems vary according to ethnic groups.
      For instance, Asian women seem to have less problems after menopause than their
      occidental counterparts. Nevertheless, the problems do exist and seem to be
      increasing due to the longer life expectancy and lifestyle changes of people in
      the region. Clinical decision in menopausal therapy can be determined according
      to health risk stratification. Appropriated menopausal therapeutic strategies
      include medical and non-medical modalities. The non-medical modalities are mainly
      focussed on lifestyle modification, while the medical modalities are classified
      as hormone replacement therapy (HRT) and non-HRT. Those in the high risk group
      will probably benefit most from medication besides lifestyle modification. There
      are various types, doses, routes and regimens of medication which need to be
      appropriately matched with the proper women's characteristics. Those who have
      contraindications to HRT or can not tolerate its side effects may choose other
      alternatives eg, selective estrogen receptor modulators, bisphosphonates,
      calcitonin or calcium and vitamin D. The success of menopausal therapy is to give
      an appropriate therapeutic option to the right woman. The future direction of
      research will remain focussing on the development in diagnosis and menopausal
      therapy particularly the main three areas of health promotion, disease prevention
      and treatment. The trend of research and development will probably be
      concentrated on new pharmaceutical agents with more specific action and high
      selectivity in an attempt to maximize its efficacy and safety. Attention may be
      paid more on the convenience of drug administration to increase its compliance.
      Alternative medicine and appropriated technologies are also the fields of special
      interest of which research is underway.

PMID- 12188397
TI  - Ethical issues in research grant applications.

PMID- 12188399
TI  - Diagnosis method of Helicobacter pylori infection in bleeding peptic ulcer.
AB  - Peptic ulcer lesions are the most frequent cause of upper gastrointestinal
      bleeding and are responsible for more than 50 per cent of cases. Several
      etiologic factors of peptic ulcer are known, the principle one being Helicobacter
      pylori (H. pylori). Recent studies indicate that H. pylori eradication is
      associated with the marked reduction in rebleeding rate. In peptic ulcer bleeding
      which requires surgical intervention, knowledge H. pylori status may help to
      determine the choice of procedure (simple sewing in H. pylori positive patients
      vs full-blown ulcer surgery in H. pylori negative patients). We suggest to use
      the invasive combination of histology and biopsy-rapid urease test in stable
      bleeding peptic ulcer patients without coagulopathy for H. pylori diagnosis.
      Cases with positive result do not need further investigation for H. pylori
      diagnosis. If negative, the serology test was suggested to confirm the absence of
      H. pylori. However, in unstable patients, the serology test seem to effectively
      detect H. pylori infection.

PMID- 12188400
TI  - Streptococcus suis infection in Thailand.
AB  - This is a retrospective study of Streptococcus suis infection in humans submitted
      to the National Streptococcal Referrence Center of Thailand from 1994 to 2001.
      There were 11 men and 6 women whose mean age was 46.24 years (range 1 month to 75
      years). Among the men, two had known occupational and behavioral exposure to pork
      or meat products. Among the women, one was a butcher and three were housewives.
      Half of the patients had underlying diseases. One patient had congenital
      hydrocephalus, three patients had rheumatic heart disease and three were
      alcoholics. Two of these patients had a history of skin injury before infection.
      Nine patients had evidence of acute bacterial meningitis, four patients had
      infective endocarditis, two had the sepsis syndrome and two suffered from
      pneumonia and spontaneous bacterial peritonitis. The authors suspected that many
      cases are not reported particularly where pig-rearing or pork consumption are
      common. In the absence of an effective vaccine, prevention by public health
      surveillance is important. Prompt treatment of any cuts and wounds among pork
      handlers is a sensible precaution. Furthermore, a high index of suspicion and
      early detection in order to identify and apply effective antimicrobial agents is
      necessary to successfully treat S. suis infection.

PMID- 12188401
TI  - A randomized crossover study to evaluate LDL-cholesterol lowering effect of a
      generic product of simvastatin (Unison Company) compared to simvastatin (Zocor)
      in hypercholesterolemic subjects.
AB  - It is agreed that people with a high blood LDL-cholesterol level will have a
      higher risk of coronary heart disease (CAD) than those with low blood LDL
      cholesterol level. Because of the present National Drug Strategy of Thailand, the
      promotion of "in-country production" of a generic drug has been established.
      Simvastatin is one of the drugs in this strategy. In this, the primary report of
      a randomized crossover study with washout period for a cholesterol lowering
      effect in a generic product of simvastatin (Unison company) which was compared to
      the original simvastatin (Zocor) hypercholesterolemic to the subjects were
      presented. Simvastatin used in this study were derived from two sources. The
      first group was the original product (Zocor), dosage 10 mg, Lot No IC4/36(N) from
      Merck Sharp & Dohme Company and the second group was a generic product, dosage 10
      mg, Lot No T05/080 and T06/109 from Unison Company. All simvastatin tablets from
      the first and second sources were inserted into closed capsule of the same shape
      and called drug A and drug B, respectively. Both the physician in-charge and the
      subjects in this study were blinded for the content inside the capsule (Double
      blind). Thirty drug capsules were put into a sachet and distributed to the
      subject at each visit. The interval between each visit was 4 weeks. All subjects
      were asked to bring back the residual capsule within the sachet to the researcher
      at each visit in order to evaluate the subject's compliance. All subjects had
      physical examination and blood tests at each visit. Furthermore, all subjects
      were advised to practice diet control and regular in-take of the drug capsule
      daily after their evening meal. All 48 subjects were randomly allocated into 2
      groups. This study was run as a randomized crossover study. After taking the
      drugs for the first 8 weeks, no statistically significant difference of blood LDL
      cholesterol between the first and second group was detected. After a 4 week
      washout period, crossover and taking the drugs for the last 8 weeks, no
      statistically significant difference of blood LDL-cholesterol between the first
      and second group was detected. At the end of this study, comparing both groups by
      ANOVA crossover test, no statistically significant difference of blood LDL
      cholesterol between the first and second group was detected.

PMID- 12188402
TI  - Psychiatric disorders in Thai school-aged children: I Prevalence.
AB  - BACKGROUND: The prevalence of child psychiatric disorders has been studied in
      many countries. In Thailand, this was done ten years ago by using parent and
      teacher reported questionaires without interviewing the parent or the child.
      METHOD: A two-stage survey design was used in a community sample of 1698 grade 4
      school-children randomly selected from 107 schools in Bangkok. Measures employed
      were Thai Youth Checklist (TYC)-Parent and Teacher form for screening. Child and
      Adolescent Psychiatric Assessment (CAPA) was used in the second phase for 127
      parent and child interview. RESULTS: The overall prevalence rate of child
      psychiatric disorders among 8-11-year-olds was estimated to be 37.6 per cent. The
      prevalence rate were 10.8 per cent, 9.7 per cent, 7.1 per cent, 5.5 per cent, 5.1
      per cent and 5 per cent for overanxious, specific phobic, depressive, conduct,
      attention deficit-hyperactivity and separation anxiety disorders. CONCLUSIONS:
      Rates of behavior disorders were similar to those reported from other countries,
      whilst rates of emotional disorders were higher than reported elsewhere.

PMID- 12188403
TI  - Psychiatric disorders in Thai school-aged children: II Associated factors.
AB  - BACKGROUND: Many factors have been studied and found to be associated with
      psychiatric disorders in children. In Thailand, some have been studied but they
      did not cover the wide range of important factors. METHOD: A two-stage survey
      designed was used in a community sample of 1698 Grade 4 children randomly
      selected from 107 schools in Bangkok. Thai Youth Checklist (TYC)-Parent and
      Teacher form were used in the screening phase together with self-report
      questionaires to be answered by parent about general information concerning the
      child and the family. Child and Adolescent Psychiatric Assessment (CAPA) was used
      in the second phase for 127 parent and child interview. RESULTS: Factors which
      are significantly associated with behavior and emotional problems are family
      discord, large family with more than 4 children, death of family members in the
      previous 6 months, children not living with biological parents, parental mental
      illness, substance abuse or criminal record and children who repeated grade at
      school. CONCLUSION: Factors associated with behavior and emotional problems are
      not different from those reported from other studies. However, children with
      physical illness was not found to be associated with higher risk in this study.

PMID- 12188404
TI  - Extended replacement of aorta in chronic type A aortic dissection.
AB  - BACKGROUND: Chronic type A dissection is itself an indication for urgent surgery.
      Usually, replacement of the ascending aorta alone is adequate. Arch and
      descending aortas are replaced only in rare occasions-impending rupture,
      dilatation with diameter >5 cm. Extended replacement of the proximal aorta is
      associated with high morbidity and mortality. Staged repair is usually
      recommended by many centers. The disadvantages are the requirement for two stage
      operations, rupture of descending aorta in the interim period and patient denial
      to have the second stage. The authors use one stage operation in such patients.
      PATIENT AND METHOD: A retrospective study of three patients who presented with
      chronic type A aortic dissection. Two patients were male and one was female, aged
      65, 67 and 70 years old. All of them had a history of hypertension. One patient
      also had severe left main coronary stenosis and total occlusion of theright
      coronary artery. Clamshell incision was used for two patients and median
      sternotomy for one. Profound systemic hypothermia and circulatory arrest was used
      for replacement of the aortic arch first. Reperfusion of the brain was performed
      via a side graft to the main graft. And then proximal ascending aortic-graft
      anastomosis was performed, followed by descending aortic anastomosis. Distal
      coronary anastomoses were performed during the rewarming period followed by
      proximal anastomoses to the aortic grafts. RESULTS: The circulatory arrest time
      was 38, 18 and 25 minutes. There was no reoperation for excessive post-operative
      hemorrhage. There was no lung contusion or injuries to left phrenic and left
      recurrent laryngeal nerve. All patients were alert and the time of endotracheal
      extubation was 16, 18 and 88 hours. One patient developed right pneumothorax
      after removal of the chest drain. Otherwise, all three patients survived without
      any complications. CONCLUSION: In some patients who need extended replacement of
      proximal aorta, replacement of aortic arch first under circulatory arrest is a
      safe technique. Clamshell incision offers better exposure than median sternotomy.
      Because of the brief period of circulatory arrest, neurologic complications are
      rare.

PMID- 12188405
TI  - Intraaortic balloon entrapment--a rare complication of intraaortic balloon pump.
AB  - Intraaortic balloon entrapment syndrome is a rare complication of intraaortic
      balloon catheter. The leakage of blood into the balloon produces clots if the
      catheter is not immediately removed. Later removal is usually not possible and
      can be complicated by laceration of the aorta or its branches. The authors report
      a seventy year old woman who had an intraaortic balloon inserted via her right
      femoral artery because of heart failure secondary to severe coronary artery
      stenosis. Blood appeared in the balloon before emergency coronary artery bypass
      grafting, but the catheter was left to be removed after surgery. After successful
      triple coronary bypass grafting, pulling the catheter resulted in hypovolemic
      shock secondary to avulsion of the right common iliac artery. Immediate
      laparotomy and replaement of the torn artery with prosthetic vascular graft was
      successfully performed. This rare and life threatening complication of
      intraaortic balloon catheter can be prevented by immediate removal of the
      catheter when blood appears in the balloon.

PMID- 12188406
TI  - Surgical management for type A aortic dissection: 38 cases experience in King
      Chulalongkorn Memorial Hospital: early result and longterm follow-up.
AB  - OBJECTIVE: The objective of the present study was to evaluate the outcome of
      operative treatment for type A aortic dissection during the past 8 year period.
      PATIENTS AND METHOD: From January 1992 to March 2000, 38 patients (24 men and 14
      women) underwent operations for acute (n = 26) and chronic (n = 12) type A aortic
      dissection. Patient's age ranged from 24 to 82 years (mean age 56 years).
      Surgical procedures included supracoronary ascending aortic graft for normal
      sinuses and valve (n = 34) with valve resuspension for commissural detatchment (n
      = 2), composite valve and ascending aortic graft for abnormal sinuses and valve
      (n = 1), and valve replacement and supracoronary ascending aortic graft for
      normal sinuses and abnormal valve (n = 1). Resection was extended into the arch
      and descending aorta in chronic dissection if there was excessive dilatation of
      the arch and descending aorta (n = 3). In 28 patients, aortic graft replacement
      was accomplished by proximal and distal anastomoses during aortic cross-clamping
      just proximal to the innominate artery. In 10 patients, deep hypothermia and
      circulatory arrest was used for open distal anastomosis or for arch replacement.
      Simultaneous coronary artery bypass grafting was performed in 4 patients. Pre
      operative risk factors and the condition of the patients were defined and post
      operative morbidity and mortality were followed in the early and long term
      period. RESULTS: There were 2 post-operative deaths (5.2%); one patient died of
      acute renal failure, the other patient had intra-operative rupture of the heart
      chamber; both were operated on in the acute phase of dissection. Complications
      included sternal wound infection in one case, neurological complication in two
      cases, respiratory problems in three cases, pericardial effusion in one case and
      post-operative bleeding that required re-operation in five cases. There was no
      hospital mortality in the group that were operated on in the chronic phase of
      dissection. Patient follow-up ranged 2 months to 8 years, there were two late
      mortalities, both, from acute myocardial infarction (at 33 days and 2 years after
      surgery). Survival rate was 92 per cent and 86 per cent at 30 days and 2 years,
      respectively. CONCLUSION: The result of repair of type A dissection in both
      phases was good in our center. The operative mortality was 5.2 per cent.
      Predictive factors of mortality were pre-operative shock (p=0.021), tamponade
      (p=0.021) and operation in the acute phase of dissection (p=0.042). In chronic
      type A dissection, the operative mortality was zero. Coronary artery disease was
      the most common cause of late deaths. Intermediate term survival in the present
      series was satisfactory.

PMID- 12188407
TI  - Current knowledge in falciparum malaria-induced acute renal failure.
AB  - Plasmodium falciparum is highly prevalent in the tropics. Acute renal failure
      (ARF) is a common complication in severe falciparum malaria. The disorder is
      usually oliguric or anuric and hypercatabolic. Acute tubular necrosis (ATN), the
      principal pathologic lesion in falciparum malaria-induced ARF, is mediated by a
      complex interaction of mechanical, immunologic, cytokine, humoral, acute phase
      response, non specific factors, and hemodynamics factors. Parasitized
      erythrocytes express a central role in all aforementioned pathogenic factors of
      ARF.

PMID- 12188408
TI  - A capsular dilatation facilitated shoulder manipulation for treating patients
      with frozen shoulder.
AB  - Forty patients with a diagnosis of frozen shoulder who had symptom for an average
      of 8 months and failed conservative treatment of at least 6 weeks of physical
      therapy were treated with capsular dilatation facilitated shoulder manipulation.
      Post-manipulation, the patient underwent arthroscopy for visualization, fibrin
      debridement and bleeding point coagulation. All the essential intra-articular
      structures ie, glenohumeral ligament, rotator cuff were intact. Post-operatively,
      all patients revealed substantial gain in shoulder range of motion as well as
      diminished shoulder pain. The average flexion, abduction, and internal rotation
      gain were 76.9+/-8.9, 18.1+/-5.7, 9.6+/-7.1 degrees respectively. External
      rotation gain in the position of 90 degrees shoulder abduction and shoulder
      adduction were 53.0+/-9.97 and 31.4+/-7.2 degrees respectively. The average pain
      score by visual analogue scale pre and 6-month post-manipulation were 80.6+/-8.6
      and 7.6+/-7.3 respectively with the average of pain score of 73.0+/-10.4. The
      authors proposed an effective and safe technique employing intra-articular
      pressure to facilitate shoulder manipulation in order to treat frozen shoulder.

PMID- 12188409
TI  - Effect of the "sitting pelvic tilt exercise" during the third trimester in
      primigravidas on back pain.
AB  - A single center, prospective, randomized, single blinded, controlled study
      comparing the effects and safety of "sitting pelvic tilt exercise" in relieving
      back pain during the third trimester in primigravida was carried out. The samples
      were composed of 67 primigravidas who attended the prenatal clinic at King
      Chulalongkorn Memorial Hospital. All subjects were selected by the random
      sampling technique and allocated into two groups for the experimental group and
      the control group; for 32 and 35 pregnants, respectively. The experimental group
      received the pelvic tilt exercise program for 8 weeks during the third trimester.
      Pain intensity was measured by visual analogue scale (VAS) at day 0 and day 56 in
      both groups. The result of the study revealed 1) The mean VAS of back pain in the
      experimental group was significantly lower at day 56 than at day 0 and lower than
      the control group at day 56 (p< 0.05) by unpaired t-test 2) There was no
      incidence of preterm labor, low birth weight or neonatal complication in the
      experimental group. In conclusion, the "sitting pelvic tilt exercise" during the
      third trimester in primigravidas could decrease back pain intensity without
      incidence of preterm labor, low birth weight or neonatal complication.

PMID- 12188410
TI  - Efficacy of chamomile-extract spray for prevention of post-operative sore throat.
AB  - A randomized, double-blind study was carried out to assess the effect of 111 mg
      of Chamomile extract spray compared with normal saline spray (placebo)
      administered before intubation on post-operative sore throat and hoarseness. One
      hundred and sixty-one ASA (American Society of Anesthesiologists) physical status
      I, II elective surgical patients were recruited. Forty-two out of 80 patients
      (52.5%) in the Chamomile group scored no post-operative sore throat in the post
      anesthesia care unit compared with 41 out of 81 patients (50.6%) in the placebo
      group, p=0.159. Post-operative sore throat and hoarseness both in the post
      anesthesia care unit and 24 hour after operation were not statistically
      different. There was no statistically significant relationship between sore
      throat or hoarseness and ASA physical status, sex, history of smoking, grade of
      laryngoscopic view, number of intubation attempts, condition during intubation
      and condition of extubation. However, there was significant correlation between
      use of oral airway and sore throat in the post-anesthesia care unit and 24 hours
      after operation (p=0.031 and 0.002 respectively). Chamomile extract spray
      administered before intubation, therefore, can not prevent post-operative sore
      throat and hoarseness.

PMID- 12188411
TI  - Parental presence during induction of anesthesia in children: a study on parental
      attitudes and children's cooperation.
AB  - Parental attitudes and children's cooperation towards parental presence during
      induction of anesthesia (PPIA) were studied in one hundred parents and one
      hundred children aged 1-10 years. The dimensions of parental attitudes were how
      much PPIA is beneficial or harmful to their child, whether their presence could
      help the anesthetist, whether the parents should be present and their feelings
      during induction of anesthesia. Before and after induction of anesthesia
      respectively, 83 per cent and 87 per cent of the parents thought their presence
      was mostly beneficial to their child, 77 per cent and 83 per cent thought their
      presence was least harmful, 64 per cent and 71 per cent believed their presence
      could help the anesthetist and 97 per cent of the parents agreed that parents
      should be present during induction of anaesthesia. From the children,
      perspective, 86 per cent of the children cooperated with induction. It was
      concluded that PPIA was well accepted by the parents and the majority of the
      children were cooperative.

PMID- 12188412
TI  - Estrogen and progesterone receptors status in Thai female breast cancer patients:
      an analysis of 399 cases at King Chulalongkorn Memorial Hospital.
AB  - A retrospective review was performed on 576 patients who have been diagnosed
      breast cancer and referred to Division of Radiation Therapy, Department of
      Radiology, King Chulalongkorn Memorial Hospital between January 1995-September
      2001. There were three hundred ninety nine cases of invasive breast cancer that
      available for estrogen (ER) and/or progesterone (PR) receptor status. The mean
      and median age in our study were 49.6 year and 49.0 year respectively. About 60.9
      per cent of the patients were pre and peri-menopause and 37.8 per cent were post
      menopause. Most of the histological cell type were invasive ductal carcinoma
      which comprised of 92.7 per cent. Histologic grading were nearly equal for
      moderately and poorly differentiated grade: 43.66 per cent and 40.66 per cent.
      The results of our study showed 53.4 per cent of 399 patients had ER positive and
      42.1 per cent of 380 patients had PR positive. The proportion of ER+PR+, ER+PR-,
      ER-PR+, and ER-PR- were 36.31 per cent, 15.53 per cent, 5.79 per cent and 42.37
      per cent respectively. Older age and post-menopause women had higher ER+. While
      patients with increase tumor size, poorly differentiated grading, increase
      positivity of axillary lymph nodes and higher stage have more chance of ER
      negative and PR negative.

PMID- 12188413
TI  - Relationship between vesicoureteral reflux and renal cortical scar development in
      Thai children: the significance of renal cortical scintigraphy and direct
      radionuclide cystography.
AB  - Relationship of vesicoureteral reflux (VUR), urinary tract infection (UTI) and
      subsequent renal scarring nowadays is still in question. This study aimed to
      determine 1) the incidence of cortical scarring in Thai children presenting with
      upper urinary tract infection, 2) the association between VUR with acute
      pyelonephritis and subsequent renal scarring, 3) the use of DMSA and direct
      radionuclide cystography (DRNC) scintigraphy in children with UTI. Sixty newly
      diagnosed UTI children underwent DRNC and Tc-99m DMSA renal cortical scintigraphy
      at the time of first UTI diagnosis and 6 months later. There were no significant
      differences of age, sex, type of antiobiotics and pathogens (E. coli vs non-E.
      coli) between those who did and did not develop scars (p>0.05). 58/98 of 1st DMSA
      abnormal kidneys (59.18%) developed scars. 60.20 per cent of 98 positive 1st DMSA
      had VUR while 80.33 per cent of 61 with VUR had positive 1st DMSA. 59.02 per cent
      of these 61 kidneys developed scars. Scar occurrence were 18.7 times in high
      grade VUR compared to low grades. In conclusion, there was a high incidence of
      acute pyelonephritis in the presence of VUR but acute pyelonephritis does not
      necessarily need VUR for its development. High grade reflux with upper UTI, is a
      strong indicator for renal scarring. Children presenting with UTI, irrespective
      of age, sex, or pathogen, should have both DMSA and DRNC scintigraphy performed
      to identify upper UTI and high risk patients who will develop subsequent renal
      scarring.

PMID- 12188414
TI  - Hysterosalpingographic accuracy of peritubal adhesion.
AB  - The purpose of this study was to determine diagnostic accuracy of
      hysterosalpingography by using different diagnostic criteria in peritubal
      adhesion diagnosis. The authors retrospectively reviewed cases in which both
      hysterosalpingography and laparoscopy were performed. Fifty-nine of 84 cases had
      laparoscopy proved peritubal adhesion. Five hysterosalpingographic signs
      (convoluted tube, vertical tube, ampullary dilatation, peritubal halo and
      loculation of the spillage of contrast material) defined by Karasick and Goldfarb
      were used to diagnose peritubal adhesion. All cases were analyzed by two
      different diagnostic criteria: first diagnostic criterion, presence of one or
      more signs means abnormal; second diagnostic criterion, presence of two or more
      signs means abnormal. Peritubal adhesion was diagnosed in 70 of 84 cases by using
      the first diagnostic criterion, 53 of 84 cases by using the second diagnostic
      criterion. The first diagnostic criterion displayed 94.9 per cent sensitivity, 44
      per cent specificity, 80 per cent positive predictive value, 79.76 per cent
      accuracy and the likelihood ratio of 1.69. The second diagnostic criterion showed
      74.6 per cent sensitivity, 64 per cent specificity, 83 per cent positive
      predictive value, 71.43 per cent accuracy and the likelihood ratio of 2.07. The
      authors conclude that using the 2nd diagnostic criterion is more appropriate than
      using the 1st diagnostic criterion in diagnosing peritubal adhesion.

PMID- 12188415
TI  - Infectious keratitis at King Chulalongkorn Memorial Hospital: a 12-year
      retrospective study of 391 cases.
AB  - A retrospective study of 391 severe infectious keratitis admitted to King
      Chulalongkorn Memorial Hospital from January 1988 to December 2000 were analyzed.
      Most patients came from the central part of Thailand. There were 2 bimodal peak
      incidence distributions which fell in the age group 21-30 and 51-60 years of age.
      The most common predisposing to corneal ulceration was trauma from several
      materials, including leaves, branches, dust and stone, which accounted for 47.82
      per cent. Culture results were collected 74.68 per cent (292/391). The data
      showed negative culture results of 52.74 per cent (154/292), positive results
      occurred in 47.26 per cent (138/292); including bacteria 32.53 per cent (95/292),
      fungus 11.64 per cent (34/292), virus 2.05 per cent (6/292) and mixed organism
      1.02 per cent (3/292). Pseudomonas aeruginosa was the most common bacteria
      isolated; 47 per cent. The second most common was Streptococcus pneumoniae which
      accounted for 9 per cent. Fusarium spp was the most common fungus found (34.29%);
      Aspergillus and Curvularia spp were the next (20.0% each). Herpes simplex was the
      most common virus isolated; 83.3 per cent. The treatment of infectious keratitis
      included application of topical/intraocular injection of antimicrobial agent and
      surgery, which accounted for 184 cases. Penetrating keratoplasty was the most
      common surgery performed, 34.24 per cent (63/184), followed by evisceration and
      enucleation accounted for 25 per cent (46/184).

PMID- 12188416
TI  - Corneal arcus associated with dyslipidemia.
AB  - A cross sectional study based on 243 subjects with an age range of 20-63 years,
      was conducted to assess the prevalence of corneal arcus and the association
      between corneal arcus and dyslipidemia which is a coronary heart disease risk
      factor. The presence of corneal arcus was determined by hand-held slitlamp, serum
      lipids and serum plasma glucose collected on the same day as corneal arcus
      detection. Total cholesterol (CHOL), triglyceride (TG) and high density
      lipoprotein (HDL) were measured by enzymatic procedure, and low density
      lipoprotein (LDL) was estimated by the Friedewald formula. The prevalence of
      corneal arcus was divided into 3 age groups, 20-29 years (0%), 30-49 years (male
      41.5%, female 26.13%) and 50-69 years (male 86.2%, female 59.1%) In the 30-49
      year, female group, those with corneal arcus had higher serum LDL and total
      cholesterol concentration than those without corneal arcus. The mean difference
      of LDL was 22.21 mg/dl (p=0.001) and total cholesterol was 30.95 mg/dl (p=0.000).
      In the 30-49 year, male group people with corneal arcus had a lower serum HDL
      concentration than those without corneal arcus and the mean difference of the HDL
      was 8.6 mg/dl (p=0.014). There was no difference for corneal arcus and serum
      lipid in the 50-69 years group in both sexes. No association between corneal
      arcus and fasting plasma glucose was found in all ages and both sexes. It is
      concluded that while corneal arcus is primarily an aged-related change, if
      present in people under 50 years it should be considered for dyslipidemia which
      is one of the risk factors for coronary heart disease.

PMID- 12188417
TI  - The effect of cigarette smoking on urinary hippuric acid concentration in Thai
      workers with occupational exposure to toluene.
AB  - Urine hippuric acid determination is helpful for monitoring of group of workers
      at risk for exposure to toluene. However, some problems about the external source
      of variation are mentioned. Some studies have indicated that smoking is an
      important external source of variation for determination of urine hippuric acid
      level while the others stated the opposite findings. This study was conducted in
      an attempt to study the difference of urine hippuric acid between smoking and non
      smoking subjects in a press workers group. Urine samples were obtained from 46
      workers (all male) who worked as press workers in the same press factory in
      Bangkok. The individuals were classified as control (non smoking, N = 26) and
      experimental (smoking, N = 20) according to their smoking. All samples were
      analyzed for hippuric acid level. The average urine hippuric acid level for the
      control were (0.35 +/- 0.31 mg/gCr) and experimental group (0.40 + 0.45 mg/gCr)
      were respectively. No significant difference was found between urine hippuric
      acid level between both groups. The data from the current study indicates that
      smoking does not influence the urinary hippuric acid levels in this study group.

PMID- 12188418
TI  - Expected value of serum soluble transferrin receptor, erythropoietin and ferritin
      and their correlation among healthy non-anemic Thai children.
AB  - Transferrin receptor (TfR) is a glycoprotein which mediates the entry of ferric
      transferrin from the extracellular compartment into the cells. The measurement of
      sTfR has become a widely used tool in assessing erythropoiesis but its use has
      mainly been restricted to research laboratory settings. In Thailand, there are
      only a few reports concerning the sTfR. The authors studied the expected value of
      sTFR as well as other basic parameters for monitoring of erythropoiesis as
      erythropoietin (EPO) and ferritin among a sample of non-anemic healthy Thai
      children. In addition, correlation was done between each pair of studied
      parameters. Expected range for sTfR level for the healthy controls in this study
      was 1.761 to 2.034 mg/L. Expected range for serum EPO level for the healthy
      controls in this study was 19.445 to 34.176 mU/ml. Expected range for serum
      ferritin level for the healthy control from this study was 67.895 to 96.692
      ng/ml. Of interest, poor correlation among the three studied parameters, sTfR,
      serum EPO and serum ferritin was observed in this study.

PMID- 12188419
TI  - Evaluation of the Sysmex UF-100 automated urinalysis analyzer and comparative
      study with JCCLS reference method.
AB  - Microscopic urine sediment analysis has been accepted as the mainstay test for
      examining urine cells and particles. Although it provides essential information
      for clinicians about disease states in the patients, it is a high-volume and
      laborious procedure. Therefore, an automated analyzer was developed recently and
      has just been introduced to Thailand. In this study, the authors evaluated the
      analytical performance of this new automated urine analyze. Also a comparative
      study was performed between the UF-100 test results and those of JCCLS reference
      method. In evaluation of the Sysmex UF-100 automated urinalysis analyzer, both
      precision and linearity studies were performed. Between-run CVs for RBCs (mean =
      182.46/microl), WBCs (mean = 193.37/microl), ECs (mean = 70.05/microl) and casts
      (mean = 12.21/microl) were 7.74 per cent, 5.52 per cent, 21.32 per cent and 7.69
      per cent, respectively. Concerning the within-run CVs for the RBC analysis, the
      CV ranged from 16.28 per cent for low numbers of RBCs (35.67/microl) to 2.93 per
      cent at RBC concentrations (712.13/microl). Concerning within-run precision for
      the WBC analysis, the CV ranged from 22.31 per cent for low numbers of WBCs (WBCs
      12.53/microl) to 2.07 per cent at a WBC count of 211.01/microl. Within-run
      precision ranged from 11.36 per cent at 24.99 ECs/microl to 6.18 per cent at
      53.08 ECs/microl. Within-run precision for casts varied from 35 per cent for
      samples with 1.33 casts/microl to 12.38 per cent for samples with 4927.35
      casts/microl. From the comparative study, good agreements (p < 0.05) were
      obtained between UF-100 and JCCLS reference method for RBCs counts (p = 0.000, r
      = 0.974) and WBCs counts (p = 0.000, r = 0.913). However, fair agreement (p >
      0.05) was obtained between UF-100 and JCCLS reference method for ECs counts (p =
      0.017, r = 0.212) and casts counts (p = 0.624, r = 0.044). In conclusion, the UF
      100 analyzer is a new useful analyzer although it cannot be a substitute for
      microscopic sediment examination.

PMID- 12188420
TI  - Dengue infection: a global concern.
AB  - Dengue infection, one of the most important mosquito-borne viral diseases of
      humans, is now a significant problem in several tropical countries. The disease,
      caused by the four dengue virus serotypes, ranges from asymptomatic infection,
      undifferentiated fever, dengue fever (DF) to severe dengue hemorrhagic fever
      (DHF) with or without shock. DHF is characterized by fever, bleeding diathesis
      and a tendency to develop a potentially fatal shock syndrome. Hematological
      findings include vasculopathy, coagulopathy and thrombocytopenia as the most
      constant findings. During the last twenty-five years, there have been increasing
      reports of dengue infection with unusual manifestations, mainly with cerebral and
      hepatic symptoms. Laboratory diagnosis includes virus isolation, serology and
      detection of dengue ribonucleic acid. Successful treatment, which is mainly
      supportive, depends on early recognition of the disease and careful monitoring
      for shock. Prevention depends on control of the mosquito vector. More efforts
      must be made to understand the pathogenesis of DHF in order to develop a safe and
      effective dengue vaccine.

PMID- 12188421
TI  - Situation of laboratory service and instruments in Thailand: a descriptive study
      from questionnaires.
AB  - Laboratory instruments are one of the main items in laboratory investment. To
      establish data for the situation of laboratory service and instruments in
      Thailand, questionnaires were randomly sent to one hundred and twenty
      laboratories. Sixty-three filled questionnaires from eleven university and
      affiliated hospitals, thirty-four government hospitals, and eighteen private
      hospital laboratories were sent back to the authors to be analyzed. Only the
      number of samples and instruments used during office hours were analyzed in this
      study by descriptive method. From the data it was found that the average number
      of personnel and tests of the university and affiliated hospital laboratories was
      the highest. To analyze the efficiency of the instruments used in the
      laboratories, the authors compared the average service number of samples or tests
      to the average number of samples or tests that was calculated from the
      instruments. The ratio of the average number of samples or tests that were
      calculated from the instruments and the average service number of samples or
      tests for chemistry and CBC were 2.13, 3.41, 5.24 and 2.33, 2.76, 3.71 in
      university and affiliated hospital laboratories, government hospital
      laboratories, and the private hospital laboratories, respectively. From the data,
      it was concluded that the instrument situation in laboratories of the university
      and affiliated hospitals was more appropriate than government hospital and
      private hospital laboratories. To improve the efficiency of using laboratory
      instruments, more concern must be given to the management of laboratory
      instruments and cooperation between hospitals could increase the efficiency of
      the instrument investment.

PMID- 12188422
TI  - Sitting height and subischial leg length of Thai schoolboys in Bangkok.
AB  - Anthropometry is an important way to evaluate a child's growth pattern. The
      measurement of sitting height helps to define body proportion. Every country
      should have its own normal data and use it as a national reference. The
      measurements of standing height, sitting height, and weight were performed in
      2,650 schoolboys, aged 11-18 years, and then the subischial leg length, and the
      sitting height/height (SH/H) ratio were calculated. The results were compared to
      the data of British boys studied by Tanner et al. The authors found that, in boys
      aged less than 15 years, the sitting height in Thai schoolboys was similar to
      that of British boys but the subischial leg length was longer. However, the
      sitting height and subischial leg length in Thai schoolboys became shorter than
      that of British boys after 15 years of age. This resulted in shorter adults when
      compared with British boys. In addition, the SH/H ratio in Thai schoolboys was
      the same as that in British boys when they reached the near final height. More
      data in both genders should be studied in order to construct our national
      references.

PMID- 12188423
TI  - Clinical, pathological, and electron microscopic findings in two Thai children
      with Pompe disease.
AB  - The authors report on a Thai boy who first presented at age 7 months and an
      unrelated Thai girl in her neonatal period with hypotonia, cardiomegaly and
      hepatomegaly. Their chest roentgenograms showed markedly enlarged hearts, EKGs
      showed abnormally shortened PR intervals with gigantic QRS complexes, and
      electron microscopic studies of their skin samples showed glycogen accumulations
      surrounded by membranes. The boy died at age 22 months and the girl at age 9
      months due mainly to cardiorespiratory failure. Autopsy of the girl showed marked
      accumulation of glycogen in the liver, heart and numerous additional tissues
      including her brain. The clinical, pathological, and electron microscopic
      findings of these two children are consistent with the diagnosis of Pompe
      disease. Pompe disease is an autosomal recessive disorder of glycogen metabolism
      resulting from deficiencies in activity of the lysosomal acid alpha-glucosidase.
      Definite diagnosis of the disease can be made from a biochemical test or a
      mutation analysis. To the authors' knowledge, no service laboratories in Thailand
      offer the tests. Because Thai children have occasionally been reported to be
      affected by Pompe disease, an attempt to establish a definite diagnostic test for
      Pompe disease in Thailand should be encouraged. With a definite diagnosis, the
      proper genetic counseling and prenatal diagnosis could be offered to the
      families.

PMID- 12188424
TI  - Clinical manifestation and management of hemangiomas of infancy.
AB  - A retrospective study of hemangioma seen at the Pediatric Dermatology Clinic,
      Department of Pediatrics, Faculty of Medicine King Chulalongkorn Memorial
      Hospital from June 1991 to June 2000 was conducted. A total of 197 patients with
      221 hemangiomas were followed-up from 6 months to 9 years. There were 134 girls
      and 63 boys (2.1:1), ranging in age from 6 months to 9 years. Twenty-two patients
      (11%) were premature neonates. Hemangiomas were presented at birth in 114
      patients (58%), within the first month in 65 patients (33%), and after the age of
      1 month in 18 patients (9%). Among the 197 patients, 18 patients (9%) had
      multiple locations. Types of hemangiomas were recorded as superficial, deep and
      combined in 84 (43%), 31 (16%) and 82 (41%), respectively. Head and neck were the
      most common sites of hemangiomas (65%), with 36 lesions (18%) on the trunk, 22
      lesions (11%) on upper extremities, 22 lesions (11%) on lower extremities and 15
      lesions (8%) on the perineum and buttock. Complications were found in 63 patients
      (32%) with 93 complications. Perineum and buttock had the highest rate of
      complication (60%), followed by the eyelid region (41%). Superficial hemangioma
      had the highest rate of complication (64%), followed by combined type (46%).
      Ulceration was the most common complication in the superficial and combined type.
      Obstruction was the most common complication in deep hemangioma. Management of
      hemangioma included observation, prednisolone, flashlamp-pumped pulsed-dye laser,
      topical therapy and excision in 68 per cent, 8.6 per cent, 10.7 per cent, 9.6 per
      cent, and 2.5 per cent, respectively. In conclusion, complications of hemangiomas
      are common. Close observation with regular follow-up will give better recognition
      and treatment of complications and associations.

PMID- 12188425
TI  - Adrenal functions in children with adrenoleukodystrophy.
AB  - BACKGROUND: Adrenoleukodystrophy refers to an inherited disorder that mainly
      affects the adrenal gland, and the nervous system. The most common type is X
      linked adrenoleukodystrophy (XALD). The main presenting symptoms are behavioral
      changes. However, endocrinological manifestations are also important and need to
      be clarified especially adrenal insufficiency which is a lifethreatening
      condition that can be prevented. OBJECTIVE: To review the endocrinological and
      the adrenal functions in X-linked ALD. SUBJECTS AND METHOD: The medical records
      of four patients diagnosed with ALD at the Endocrinology and Metabolic Unit,
      Department of Pediatrics, King Chulalongkorn Memorial Hospital between 1998 and
      2000 were reviewed. The diagnoses were confirmed by elevated very long chain
      fatty acid (VLCFA) levels and the typical changes seen on magnetic resonance
      imaging (MRI) of the brain. The adrenal functions in these patients were studied.
      RESULTS: All patients presented between 7-11 years of age with learning problems
      and behavioral changes, without symptoms of adrenal insufficiency such as nausea,
      vomiting and abdominal pain. However, the physical signs of adrenal insufficiency
      such as generalized hyperpigmentation particularly on the nipples, skin creases
      and genitalia were present. The laboratory investigations revealed normal blood
      sugar and serum electrolytes. The adrenal functions were revealed as follows.
      Basal ACTH levels were high in 2 cases (290, > 1,250 pg/mL). Basal cortisol level
      was low in 1 case. ACTH stimulation tests revealed subnormal responses in 3
      cases. Magnetic Resonance Imaging of the brain showed white matter degeneration
      in the occipital area in 2 cases and frontal area in 2 cases. CONCLUSION: Adrenal
      insufficiency can be detected by laboratory evaluation despite the lack of
      symptoms, therefore, the adrenal function should be evaluated in X-ALD at
      diagnosis for proper management.

PMID- 12188426
TI  - Lyophilized cryoprecipitate for children with hemophilia A.
AB  - Cryoprecipitate is the most cost-effective treatment for bleeding events in
      hemophilia A children in Thailand. Lyophilized cryoprecipitate (LC), a freeze
      dried heat-treated blood product from the National Blood Center, can be stored in
      a refrigerator. The objectives of this study were to assess the efficacy of LC in
      bleeding episodes of children with hemophilia A and to determine the
      pharmacokinetics of single dose LC infusion. Eight male children with congenital
      factor VIII deficiency, aged 1.2-13 years, with 12 active bleeding episodes were
      infused with reconsitituted LC (average factor VIII activity = 236 IU per bottle)
      at the dose of 1 bottle per 11 kg. All patients achieved clinical hemostasis by
      12 hours post-infusion. The Factor VIII activity reached peak level within the
      first hour and declined slowly in the subsequent hours and retained in vivo
      Factor VIII activity at 27.3 +/- 5.6 per cent at 12 hours post-infusion. The
      incremental factor VIII activity was 2.37 +/- 1.05 per cent (mean +/- SD) per U
      infused per kilogram body weight. The half-life of infused factor VIII was 10.5
      hours. The authors concluded that reconstituted LC infusion is efficacious in the
      treatment of bleeding episodes in children with hemophilia. Cost-effectiveness of
      this product and cryoprecipitate and other purified factor VIII should be
      evaluated.

PMID- 12188427
TI  - Hepatic dysfunction in dengue patients with various severity.
AB  - This prospective study was designed to evaluate the correlation between
      biochemical changes in hepatic function and severity of dengue infection in
      pediatric patients. One hundred and four children with a clinically and
      serologically confirmed diagnosis of dengue infection were classified into the
      non-shock group, i.e. 20 cases of dengue fever and 27 cases of dengue hemorrhagic
      fever, and the shock group comprising 57 cases of dengue shock syndrome. Liver
      function tests were performed within the first three days after defervescence or
      shock. The study showed that levels of aspartate transaminase and alanine
      transaminase were significantly higher, whereas, globulin level was significantly
      lower among patients with more severe disease (p < 0.05). Levels of albumin,
      alkaline phosphatase, bilirubin and prothrombin time were not different among the
      groups. In conclusion, hepatic dysfunction in dengue patients is a common
      condition. Patients with more severe disease have significantly higher
      transaminase and lower globulin levels.

PMID- 12188428
TI  - Resident recruitment: what are good predictors for performance during pediatric
      residency training?
AB  - The authors evaluated the value of the Cumulative Grade Point Average (GPAX),
      letters of recommendation and personal interview in predicting performance of
      first year residents at the Department of Pediatrics, Faculty of Medicine,
      Chulalongkorn University. The pre-residency data of 25 first year pediatric
      residents were compared to the results of the Pediatric In-training Examination
      (PIE) and clinical evaluation by faculty during the first 7 months of training.
      The Clinical Performance Rating Score (CPRS) developed by the Royal College of
      Pediatricians of Thailand was used for clinical performance evaluation. GPAX
      correlated strongly with PIE score (r = 0.69, p < 0.001) while letters or
      recommendation and interview score were not predictive. For the majority of
      residents who graduated from Chulalongkorn University, including the
      undergraduate program into the regression model improved this association (r =
      0.90, p < 0.001). Interview score correlated moderately (r = 0.49, p = 0.02) with
      clinical performance measured by CPRS which entailed the evaluator to assess a
      resident in 6 specific areas. GPAX and letters of recommendation showed a trend
      toward positive correlation with clinical performance, but these associations
      were weak (r = 0.32-0.39). Further analysis of letters of recommendation found a
      significant difference between the score given by evaluators in community
      hospital settings compared to the score given by medical school faculty or
      evaluators in large regional or provincial hospitals. The authors conclude that
      the cognitive function of pediatric resident candidates can be assessed reliably
      by GPAX. Research on how to adjust for the variability of GPAX given by an
      individual undergraduate program will improve the residency selection process. A
      structured interview may correlate better with global clinical performance than
      GPAX or letters of recommendation but all methods are at best moderately
      predictive of clinical performance. Improvement can be made by continuous
      evaluation and adjustment of the selection process.

PMID- 12188429
TI  - Rectus sheath hooking: alternative method of abdominal wall lifting and fixing
      for laparoscopy: a pilot cadaver bio-mechanical study.
AB  - Four bio-mechanical tests were used to study properties of the rectus sheath for
      laparoscopic abdominal access procedure and to provide surgical exposure by the
      ChulaLift gasless retractor. The profile of forces and displacement showed how
      some patients were good candidates for the gasless operation. The lifting weight
      should not excess 10 kg for minimal harm and optimal exposure. The rectus hooking
      could be an alternative choice for abdominal wall fixing during the first trocar
      entry. One-cm width hooking, the rectus sheath could withstand 18-20 kg lifting
      force. The exposure provided by the gasless technique was narrow between the
      lateral ports compared to the conventional technique. The rectus sheath could be
      hooked to provide effective fixing of the area to be penetrated by the first
      trocar, and this fascial layer could be lifted to produce exposure in the gasless
      technique.

PMID- 12188430
TI  - Dilating missile trocar for primary port establishment: a cadaver study.
AB  - The missile trocar was developed for controllable entry force, smaller fascial
      defects and post-operative pain improvement. The trocar was composed of a fascial
      dilating long-conical head and a handle. Accompanied with this trocar, the
      authors designed a rectus sheath-hooking instrument to promote negative intra
      abdominal pressure during the trocar puncture. The hooking procedure allowed room
      air to pass through the central canal of the trocar and fill the space between
      the intestinal loops and the trocar tip. The abdominal access procedure succeeded
      in forty-five attempts in fresh cadavers. No second attempt was done. The trocar
      accessed into the peritoneal cavity at every attempt without intestinal
      penetration. The missile trocar may be an alternative device for establishment of
      the primary port. Its efficacy and safety still has to be proved.

PMID- 12188431
TI  - Changes of immune system in military recruits after the training program.
AB  - The aim of the exercise was to improve body health including the immune system
      function. However, several studies have observed the suppression of immune
      response in athletes who were trained with strenuous exercise. Recruits who have
      been in the recruitment-training program for 8 weeks might also have immune
      suppression. Twenty males, aged from 21 to 23 years in Chulachomklao Royal
      Military Academy infantry battalion volunteered to participate in this study.
      They were asked to wear a Polar Accurex Plus Telemetric heart rate monitor during
      the training period. Tuberculin skin test which is the screening method for
      cellular immune responses was significantly decreased at post-training compared
      to the pre-training (p<0.02). The levels of serum IgG and IgM at pre-training,
      4th week, 8th week and one week post-training were significantly decreased at the
      initiation period, which were compared with pre-training and 4th week of training
      (p<0.01), and returned to normal at the 8th week of training and one week post
      training. The level of circulating immune cells and number of CD markers (CD3,
      CD4, CD8, and CD56) were not significantly changed throughout the training
      period. This study demonstrated that subjects who underwent the recruit-training
      program were able to improve their health after the period of training i.e., in
      the adaptation period. The decrease in the initiation period could be compensated
      with proper diet and enough rest.

PMID- 12188432
TI  - Effects of managerial intervention on drug utilization pattern at King
      Chulalongkorn Memorial Hospital.
AB  - The economic crisis in Thailand since 1997 has a major impact on all sections of
      the country including health care. There were several suggestions for reducing
      the drug expenditure budget including restriction of hospital formulary, generic
      prescribing and generic dispensing. At King Chulalongkorn Memorial hospital, the
      new hospital formulary was established and implemented in March 1998. The generic
      dispensing policy was also in place at the same time. This study aimed to
      evaluate the impact of the new implementation by comparing the prescription
      patterns in out patient departments (OPDs) of the hospital before and after the
      new hospital formulary implementation. The prescriptions from several OPDs were
      systematically stratified samplings 5 weeks before and 5 weeks after March 1st,
      1998. The information from the prescriptions including drug category, drug name,
      amount of dispensed drug, drug cost, etc. was collected and analyzed. The total
      number of prescriptions and the average number of drug items/prescription before
      and after the implementation were similar (2,049 vs 2,052, and 2.52 +/- 0.048 vs
      2.45 +/- 0.03 respectively). The total cost of the prescription, the
      cost/prescription and the cost/item seemed to be different (1,690,484 baht vs
      1,282,343 baht, 844 +/- 54.04 vs 633 +/- 41.11 and 332.58 +/- 29.59 vs 255.29 +/-
      19.98 respectively). After the implementation, physicians in the hospital
      increasingly prescribed drugs by generic name (37.1% vs 44.85%). Locally made
      drugs were also prescribed by physicians and received by patients more than
      before (9.56% vs 84.27% and 28.15% vs 60.72%, respectively). Anti-infective
      agents were studied in depth as they contribute to significant amount of drug
      expenditure. The total cost of prescribed anti-infective agents and the
      cost/prescription were increased after the implementation (223,529 vs 274,435
      Baht and 585.38 +/- 102.84 vs 772.71 +/- 147.59). The increased cost mainly came
      from the cost of anti-HIV drugs. Our data indicate that the new hospital
      formulary may have played a part on the impact of drug expenditure reduction and
      may have changed the prescribing attitude of physicians in King Chulalongkorn
      Memorial Hospital.

PMID- 12188433
TI  - Infection in Thai patients with systemic lupus erythematosus: a review of
      hospitalized patients.
AB  - Infection is a major cause of morbidity and mortality in patients with systemic
      lupus erythematosus (SLE). The authors conducted retrospective review of 488
      admissions at King Chulalongkorn Memorial Hospital during a 5-year period (1994
      1999) to determine the infectious complications in these patients. One hundred
      ninety-one patients with SL2 were admitted because of infection. Lower
      respiratory tract infection was the most commonly found in these patients (24.6%)
      followed by infections of the urinary tract (15.7%), skin (15.7%), septicemia
      (13.6%) and the musculoskeletal system (11.5%). The most common pathogens were
      Salmonella spp (12.6%), while Escherichiae coli (9.9%) and Mycobacterium
      tuberculosis (8.4), respectively.

PMID- 12188434
TI  - Chemical compositions and pharmacological effects of essential oil from the fruit
      of Zanthoxylum limonella.
AB  - Examination of chemical compositions of essential oil distilled from the fruit of
      Zanthoxylum limonella Alston (Rutaceae) revealed the presence of 33 chemical
      components. Evaluation of the oil composition was achieved by GC/MS analysis.
      Limonene (31.09%), terpin-4-ol (13.94%) and sabinene (9.13%) were found to be the
      major components. Effects of essential oil have been performed in isolated guinea
      pig ileum, rat thoracic aorta and conscious mice. The essential oil at the
      concentration of 7.68 x 10(-5)-1.92 x 10(-3) microl/25 ml, produced dose
      dependent contraction of the isolated rat thoracic aorta. These contractions were
      significantly reduced by pretreatment with prazosin (1 x 10(-7) M) and verapamil
      (1 x 10(-7) M). Its contraction was abolished in calcium free Krebs solution.
      Contractile response to the volatile oil (2 x 10(-6)-5.12 x 10(-4) microl/25 ml)
      was examined in isolated guinea pig ileum, it evoked ileal contraction in
      concentration-dependent manner and the contractions were suppressed after
      exposure to chlorpheniramine (1 x 10(-7) M) cypoheptadine (1 x 10(-7) M) atropine
      (1 x 10(-7) M) and verapamil (1 x 10(-7) M). Therefore, it could be concluded
      that the essential oil from the fruit of Zanthoxylum limonella possessed
      stimulation effect on different smooth muscle preparations by non-specific
      mechanisms. It involved the non receptor and receptor-mediated mechanism.
      Gastrointestinal stimulant effect of the essential oil was confirmed in intact
      mice since the oil significantly increased black ink movement from the stomach to
      ileo-caecal junction after oral feeding.

PMID- 12188435
TI  - Evaluation of inhouse rapid urease test for detection of Helicobacter pylori from
      gastric biopsy specimens.
AB  - Inhouse rapid urease test for detecting Helicobacter pylori was evaluated. Biopsy
      specimens were taken for inhouse urease test, commercial rapid urease CLO test,
      culture, gram stain and histology from the antrium or duodenum of patients who
      had peptic ulcer. The culture and/or histologic examination and CLO test were
      used as the gold standard. One hundred and twelve specimens were evaluated. The
      sensitivity and specificity of the inhouse urease test was 100 per cent and 90
      per cent respectively. The inhouse urease test was suitable for detecting
      Helicobacter pylori from gastric antral biopsy specimens. The medium can be kept
      in a refrigerator for up to 6 months.

PMID- 12188436
TI  - Survey of human papillomavirus infection in cervical intraepithelial neoplasia in
      Thai women.
AB  - HPV infection is known to be associated with cervical cancer development.
      Precancerous lesions named cervical intraepithelial neoplasia (CIN) are divided
      into 3 grades, i.e., CIN-1, CIN-2, and CIN-3. Here, HPV infection determined by
      PCR and dot hybridization was observed in these 3 different grades of formalin
      fixed paraffin embedded tissues. The HPV infection was demonstrated in 33.3 per
      cent of CIN-1, 36.8 per cent of CIN-2 and 75 per cent of CIN-3. Using type
      specific probes for HPV-6, 11, 16, 18 and 33, HPV-16 was the most prevalent type
      (44.44%) followed by HPV-18 (16.05%) in CIN-3. Only one HPV-18 was identified in
      CIN-1 while CIN-2 contained one HPV-6 and one HPV-18. Mixed infection was found
      in CIN-3 (12.35%). All of them had HPV-16. The cervicitis cases with normal
      histopathology were included as control. Only 2.7 per cent of HPV infection was
      shown. The relative risk of HPV infection was high in CIN-3 (OR = 107.25, 95% CI
      = 50.29-228.73). Our data confirm the association between high-risk HPV types and
      development of CIN.

PMID- 12188437
TI  - DRB1*04 subtype in Thai patients with rheumatoid arthritis.
AB  - Rheumatoid arthritis (RA) in a Thai population is significantly associated with
      HLA-DR4. The frequency of DR4 was 43 per cent in RA patients and 20 per cent in
      the healthy controls (p = 0.00008, OR = 3.06, 95% CI = 1.71, 5.52). To analyze
      which DR4 alleles were associated with the disease, the authors subtyped 52 DR4
      positive RA patients compared to 28 DR4-positive healthy controls by
      amplification with DR4-specific primers followed by direct sequencing. Six DR4
      alleles (DRB1*0401, *0403, *0404, *0405, *0406, and *0410) were found in the RA
      patient group while 5 alleles (DRB1*0401, *0403, *0405, *0406, and *0407) were
      found in the control group. Both groups were predominated by DRB11*0405, but
      there was a significant increase in the frequency of DRB1*0405 in DR4+ RA
      patients compared to DR4+ healthy controls (84.6% vs 46.4%, p = 0.0008, OR =
      6.35, 95% CI = 1.96, 21.08). DR4 which shared epitope alleles (DRB1*0401, *0404,
      *0405) were observed in 47 (90.3%) DR4+ patients and 15 (53.5%) DR4+ controls (p
      = 0.0005, OR = 8.15, 95% CI = 2.29, 33.2). In addition, the authors found that
      DRB1*0403 was significantly decreased in DR4+ RA patients compared to controls (p
      = 0.0065, OR = 0.07, 95% CI = 0, 0.67).

PMID- 12188438
TI  - Emm types of invasive group A streptococcal isolates from Thai patients at King
      Chulalongkorn Memorial Hospital from 1995-1999.
AB  - Emm (M protein gene) typing was used to analyze group A streptococcal (GAS)
      clinical isolates in Thailand from in-patients at Chulalongkorn University
      Hospital (CUH) between January 1, 1995 and December 31, 1999. Forty GAS isolates
      were recovered from blood and other sterile sites from 40 patients presenting
      with different types of infections. A variety of emm sequences (24 types) have
      been reported in this study including the identification of 2 novel emm variants
      demonstrating the diverse population of invasive GAS isolates in Thailand. The
      common emm types include emm1 (5 isolates, 12.5%), emm22 (4 isolates, 10%), emm25
      (3 isolates, 7.5%), emm61 (3 isolates, 7.5%), and STNS1033 (3 isolates, 7.5%). No
      particular emm types of GAS tend to be frequently associated with specific
      clinical presentation, complication, or anatomic site of infection. This report
      provides epidemiological information from Thailand where streptococcal infections
      and their sequelae are important public health problems. In addition, the results
      are useful for the development of a suitable M protein based vaccine in the
      future.

PMID- 12188439
TI  - Outbreak of uncommon type of group A streptococcal pharyngitis among cadets at
      the Chulachomklao Royal Military Academy, Nakhon Nayok, Thailand.
AB  - A large outbreak of group A Streptococcus (GAS) pharyngitis occurred among 285
      cadets at the Chulachomklao Royal Military Academy, Nakhon Nayok between
      September 22 and 27, 1996. An epidemiologic investigation was conducted to
      determine the source of infection. It seemed that respiratory droplets were the
      mechanism of spread, although foodborne transmission could not be excluded. To
      assess the presence of the outbreak strain in the community, conventional
      serotyping and molecular typing by emm sequencing were performed. The results
      demonstrated the advantage of molecular typing compared to serotyping and
      suggested that the outbreak was caused by the same strain. Interestingly, the
      involvement of the causative emm79 strain, which is an uncommon type of GAS
      disease, in a large number of patients may imply the invasive potential of this
      organism.

PMID- 12188440
TI  - Detection of antibody in serum and secretion for the diagnosis of Helicobacter
      pylori infection.
AB  - Helicobacter pylori plays a major role in chronic gastritis and peptic ulcer. In
      addition, it has been shown to be associated with gastric carcinoma. In this
      study, the authors compared the detection of IgG antibodies specific to H. pylori
      by enzyme-immunoassay with culture, histology and a CLO test as tools for
      diagnosis of H. pylori infection. If the criteria that patients will be
      considered as H. pylori infected only when their samples are positive by culture
      or CLO test and histology were used, the sensitivity and specificity of detecting
      IgG in sera were 96.84 and 72.04 per cent respectively. The use of serological
      test will be useful as a screening test for H. pylori infection without the need
      of endoscopy. The authors also performed the assay for detecting IgA antibodies
      in saliva and gastric juice. The sensitivity and specificity of IgA detection in
      saliva were 26.79 per oent and 75.00 per cent. As for the assay in gastric juice,
      although the specificity was as high as 91.67 per cent, the sensitivity is very
      low (22.22%).

PMID- 12188441
TI  - Amplification of P1 gene by polymerase chain reaction for detection of Mycoplasma
      pneumoniae.
AB  - Mycoplasma pneumoniae is a causative agent of human respiratory tract infection
      of which the clinical features are not significantly different from those of
      infections caused by other respiratory pathogens. The diagnosis is based
      principally on laboratory tests. Since conventional methods such as culture and
      serological tests are time-consuming, insensitive, and non-specific, polymerase
      chain reaction (PCR) was employed for laboratory diagnostics. This study was
      aimed to develop PCR method to detect M. pneumoniae by designing primers to
      amplify fragment of the P1 adhesin gene. Two protocols, PCR-probe hybridization
      and nested PCR, were carried out. False-positive result due to amplicon carry
      over was prevented by using dUTP instead of dTTP and the addition of enzyme
      uracil DNA glycosylase (UDG). For nested PCR, UDG was added only in the first
      round reaction mixture. The sensitivity of PCR was 10 fg of M, pneumoniae DNA as
      detected by agarose gel electrophoresis and increased to be 1 fg as detected by
      either probe hybridization or nested PCR. The specificity of PCR was tested with
      DNAs from Mycoplasma spp, a variety of different bacterial genera and human
      leukocyte. All gave negative results. Considering of the speed, sensitivity,
      specificity and the prevention of amplicon carryover, the developed PCR-based
      protocols were suitable and reliable for the detection of M. pneumoniae in
      routine laboratory.

PMID- 12188442
TI  - Replication of herpes simplex virus in T lymphocytes.
AB  - HSV is known to cause infection at various parts in the human body such as skin,
      mouth, eyes, genital area, and brain. In this study, the authors showed the
      possibility of HSV replication in Jurkat, a human leukemic T lymphocytes.
      Although the yield production was very low when compared to the other 2
      epithelial cells, Vero and HEp-2 cells, the yield production could enhance after
      PHA activation. Delayed viral protein expression was observed in Jurkat cells.
      This might be the reason for low production. However, the exactly mechanism is
      unknown. Replication of viruses have been examined in a number of cell systems
      and the duration of successive steps in the replication cycle depends upon the
      types of cells, the virus strain, and the multiplicity of infection.

PMID- 12188444
TI  - Comparison of methods for identification of Pneumocystis carinii in
      bronchoalveolar lavage fluid.
AB  - Pneumocystis carinii pneumonitis in one of the most common life-threatening
      opportunistic infections in patients with AIDS. The definitive diagnosis of this
      infection can be established only by demonstration of the organism in clinical
      specimens. This study was a comparison of methods that provide easy recognition
      of the organism which is readily available, simple and can be performed rapidly
      in laboratory-diagnosis. Bronchoalveolar lavage fluids obtained from 35 AIDS
      patients suspected of having Pneumocystis carinii pneumonitis were examined by
      three staining methods for the presence of Pneumocystis carinii. With Giemsa
      stains, P. carinii could be identified in 18 cases (51.4%). Three developmental
      stages: "cyst", "sporozoite" and "trophozoite" were seen. The contrast of
      organisms against host cells was not outstanding in these stains. Toluidine blue
      O stains provided easy recognition of the organisms, with marked contrast between
      the cysts and host cells. 21 cases (60%) were positive in these stains, but the
      intracystic structures and trophozoites could not be identified. It was suggested
      that the clinical specimen should be stained first with toluidine blue O which is
      more rapid and permits easy recognition of the cyst clusters. If the sporozoites
      and trophozoites had to be identified, Giemsa stains can be made. In addition,
      with the methenamine silver nitrate stains, 21 cases (60%) were positive. They
      revealed the morphology as seen with toluidine blue O but the cost of material
      may make it unavailable in many laboratories especially with the budgetary
      restraints of developing countries.

PMID- 12188443
TI  - Efficacy of benzbromarone compared to allopurinol in lowering serum uric acid
      level in hyperuricemic patients.
AB  - This study was aimed to evaluate the efficacy of benzbromarone compared to
      allopurinol in lowering serum uric acid level in hyperuricemic patients with
      normal renal function (serum creatinine < or = 1.5). The authors conducted a
      crossover study consisting of two four-week treatment periods of allopurinol 300
      mg/day and benzbromarone 100 mg/day separated by a four-week washout period.
      Fourteen patients with mean age and duration of hyperuricemia of 60.78 +/- 8.62
      and 6.93 +/- 3.69 years, respectively, were recruited and all completed our study
      protocol. This study was a crossover design consisting of two four-week
      treatments of allopurinol and benzbromarone separated by a four-week washout
      period. The serum uric acid level was reduced from 9.89 +/- 1.43 mg/dl to 5.52 +/
      0.83 mg/dl and from 9.53 +/- 1.48 to 4.05 +/- 0.87 mg/dl by allopurinol and
      benzbromarone, respectively. The efficacy of benzbromarone in lowering serum uric
      acid level was significantly superior to allopurinol (p=0.005). No patient
      reported clinical side effects during treatment with either drug. In conclusion,
      the authors have shown that benzbromarone is more effective than allopurinol in
      the reduction of serum uric acid levels in hyperuricemic patients with normal
      renal function.

PMID- 12188445
TI  - Prevalence of parasitic infections among Thai patients at the King Chulalongkorn
      Memorial Hospital, Bangkok, Thailand.
AB  - Parasitic diseases are still considered to be a major public health problem. Most
      patients with parasitic infections are asymptomatic and therefore remain
      undetected. Asymptomatic parasitic infections are usually discovered by routine
      parasite examination. To determine the result of parasite examination at the
      Parasitology Unit, Out Patient Department, King Chulalongkorn Memorial Hospital,
      Bangkok, Thailand, the authors collected the data of individuals examined for
      parasite infections from June to December 1997. A total of 6,231 Thais provided
      the data for analysis. Evidence of parasitic infections was found in 557 (8.94%)
      cases. The disease was most prevalent in males (57.3%), and in the age group >15
      30 years old (11.13%). The population from the Northeast of Thailand was found to
      harbor parasites with the highest prevalence rate (17.03%), while it was 11.90
      per cent in the northern group. The parasitic prevalence rates in the West, East,
      South and Central regions were 10.60 per cent, 8.90 per cent, 7.74 per cent, and
      4.92 per cent, respectively. The parasite most commonly identified was
      Strongyloides stercoralis (33.39%), while giardiasis was the most common
      protozoan infection (14.36%). The highest infection rates of S. stercoralis,
      hookworms, Opisthorchis viverrini, and Gnathostoma spinigerum were found in
      northeasterners. People from the North of Thailand were infected mostly with G.
      lamblia. People of working-age from northeastern as well as northern regions
      harbored pathogenic parasites with high prevalence rates. To prevent parasitic
      infections, health education for these high risk groups should be provided.

PMID- 12188447
TI  - Effects of a monophasic pill containing 20 microg ethinylestradiol and 150 microg
      desogestrel on lipid metabolism in Thai women.
AB  - OBJECTIVES: To investigate the effects of a monophasic oral contraceptive
      containing 20 microg ethinylestradiol and 150 microg desogestrel (Mercilon) on
      lipid metabolism in Thai women. METHOD: The study was carried out at the Family
      Planning Clinic of King Chulalongkorn Memorial Hospital, Bangkok, Thailand.
      Twenty women of fertile age were enrolled and treated with the study oral
      contraceptives for 12 cycles. Lipid parameters were assessed before treatment and
      periodically during treatment. RESULTS: There was a significant increase in
      triglyceride, high desity lipoprotein-cholesterol, apolipoproteins AI and AII. No
      significant changes were found in total cholesterol, low density lipoprotein
      cholesterol and apolipoprotein B. CONCLUSION: The effects of the oral
      contraceptive containing 20 microg ethinylestradiol and 150 microg desogestrel on
      lipid parameters in Thai women appear to be favorably beneficial.

PMID- 12188446
TI  - A prevalence of Cryptosporidium infections among Thai HIV-infected patients.
AB  - The prevalence of Cryptosporidium in 156 HIV-infected Thai patients who had acute
      diarrheal illness at Bamrasnaradura Infectious Diseases Hospital, was studied.
      This cross-sectional study was performed from March to August in year 2001. The
      patients ranged in age from 1 month-65 years old. A stool sample from each
      subject was stained to find the oocysts by modified Ziehl Nelson carbolfuchsin
      staining. According to the present study, a diagnosis of Cryptosporidium parvum
      infection was found in 20 patients (11 males and 9 females). The prevalence of
      cryptosporidiosis in the present series was 12.8 per cent (10.0% in males and
      19.1% in females). This infection rate between males and females was not
      significantly different. Comparing this prevalence to a report in the previous 5
      years in the same hospital, the same high rate can be seen.

PMID- 12188448
TI  - Location of quinacrine pellets in different positions of non-surgical female
      sterilization.
AB  - OBJECTIVE: To compare quinacrine pellets distribution in the uterine cavity
      between women standing up promptly after insertion and those lying down for a
      further 30-minutes. DESIGNS: Randomized controlled trial MATERIAL AND METHOD:
      Twenty women who, desired interval female sterilization, were equally randomized
      into 2 groups. Quinacrine pellets were inserted twice, one month apart in both
      groups. Transvaginal ultrasonography (TVS) was performed after insertion in order
      to locate the position of the quinacrine pellets. In group I, the TVS was
      performed after the women stood up promptly. In group II, the TVS was performed
      after the women lay down for 30-minute. The distribution of quinacrine pellets,
      measured from the uterine fundus to the lowest pellet, were compared. RESULTS:
      There was no difference at the baseline and 30 minutes measurement of both
      groups. In the first insertion, there was statistical difference of the distance
      of the quinacrine pellets when compared in the same group immediately and the 30
      minute measurement (Gr 1: 19.10+/-3.28 mm vs 22.30+/-3.50 mm); (Gr 2: 18.70+/
      3.40 mm vs 24.40+/-5.95 mm). In the same manner, the authors found statistical
      difference in the same group of the second insertion (Gr 1: 21.80+/-5.39 mm vs
      24.70+/-7.24 mm); (Gr 2 : 20.89+/-4.78 mm vs 28.30+/-7.59 mm) CONCLUSIONS: There
      was statistical difference of quinacrine pellet distribution in uterine cavity
      after time. However, body movement did not effect the position of the pellets.
      The failure rate of quinacrine pellet insertion for non-surgical female
      sterilization may not be explained by the changes of position after insertion.

PMID- 12188449
TI  - Serum beta-hCG regression after laparoscopic salpingostomy in the treatment of
      ectopic pregnancy in Thai women.
AB  - This is a descriptive study which reviewed the regression pattern of serum beta
      hCG in Thai women with ectopic pregnancy after laparoscopic salpingostomy. The
      study group included the medical records of 21 patients who underwent
      laparoscopic salpingostomy between January 1991 and August 2001. The results
      revealed that the regression of serum beta hCG in patients with ectopic pregnancy
      after laparoscopic salpingostomy was about 10, 100, 1,000 times at day 6, 20 and
      35 after operation. The correlation between days after operation and serum beta
      hCG was in the equation of log (beta hCG difference) = -0.0671 (days after
      operation) - 0.6187. This estimation curve can probably be used to predict the
      normal serum beta-hCG regression after laparoscopic salpingostomy.

PMID- 12188450
TI  - Predictive value of human chorionic gonadotropin in the outcome of early
      pregnancy achieved by assisted reproductive technology.
AB  - This study was undertaken to evaluate the predictive value of the serum human
      chorionic gonadotropin (hCG) in pregnancies achieved by assisted reproductive
      techonology (ART). Two hundred and eighty-six pregnancies were studied
      retrospectively from September 1989 to June 1998. The serum hCG samples at 2-6
      weeks after embryo transfer (ET) were analysed by fluoroimmunoassay. Pregnancy
      status was followed by ultrasonography. There were 100 nonviable pregnancies
      (NP), 140 viable single pregnancies (VSP) and 46 viable multiple pregnancies
      (VMP). The sensitivity, specificity, positive and negative predictive value of
      the D14 hCG (<160 mIU/ml) in distinguishing NP from VSP were 79 per cent, 75 per
      cent, 68 per cent and 84 per cent, respectively and of the D14 hCG (>350 mIU/ml)
      in distinguishing VMP from VSP were 82 per cent, 75 per cent, 56 per cent and 91
      per cent, respectively. In conclusion, the serum hCG may be used to predict the
      outcome of early pregnancy achieved by ART.

PMID- 12188451
TI  - Feasibility and complications of endoscopic biliary drainage in patients with
      malignant biliary obstruction at King Chulalongkorn Memorial Hospital.
AB  - Currently the best curative therapy for primary malignant biliary tumor is
      surgery. Unfortunately, many patients present at a very late stage and only
      palliative biliary drainage is possible. Usually nonsurgical palliative biliary
      drainage means either percutaneous or endoscopic approach. In this series, the
      authors reported the rate of technical success and immediate complications in
      patients with malignant biliary obstruction who underwent endoscopic biliary
      drainage. From endoscopic retrograde cholangiopancreatography (ERCP) database
      between September 2000 and October 2001, there were 273 ERCP performed for
      obstructive jaundice. Of these, 50 patients with malignant tumor underwent 80
      procedures for endoscopic biliary drainage. The patients were divided into three
      groups according to the cholangiographic findings and clinical diagnoses.
      Patients with carcinoma of the pancreatic head were categorized as group I
      (n=10). Group II (n=20) and III (n=20) were patients with extrahepatic
      cholangiocarcinoma and hilar cholangiocarcinoma respectively. All patients
      received either plastic or metallic endoprothesis placement for biliary drainage.
      All patients except two in group I had successful endoscopic treatment.
      Complications in group I, II and III were 15.4 per cent, 14.3 per cent and 53.1
      per cent respectively. Only one patient in group II developed significant
      hypotension during the procedure. Another complication was defined as post
      procedure cholangitis. In conclusion endoscopic biliary drainage was technically
      feasible in 97.5 per cent of patients who had malignant biliary obstruction. In
      patients with hilar tumor the incidence of post procedure cholangitis was high
      (53.1%). Improvement in technique, avoiding unnecessary contrast injection, and
      draining the obstructed bile duct after injecting the contrast may improve the
      outcome and decrease the rate of post procedure cholangitis in these patients.

PMID- 12188452
TI  - Linkage analyses and SCN5A mutations screening in five sudden unexplained death
      syndrome (Lai-tai) families.
AB  - Sudden Unexplained Death Syndrome (SUDS) (or in Thai Lai-tai) share the same ECG
      pattern as Brugada Syndrome: RSR' and ST segment elevation in V1 to V3. Brugada
      Syndrome is a genetic disorder with the inheritance pattern of autosomal dominant
      (using the ECG pattern and unexplained sudden death as phenotype) and the cardiac
      sodium channel gene (SCN5A) mutations caused this syndrome. To determine whether
      SUDS was associated with the same mutations as Brugada Syndrome, the authors
      performed a linkage studies on 5 SUDS families with the Brugada Syndrome ECG
      pattern and found one family could not be excluded from linkage to SCN5A.
      However, the direct sequencing in 8 reported mutations on exon 5, 12, 17, 18 and
      28 in this family failed to demonstrate the mutations. It was concluded that SUDS
      mutations maybe a novel mutation different from previously reported mutations,
      further genetic studies in SCN5A and other candidate genes might elucidate the
      molecular basis of SUDS.

PMID- 12188453
TI  - Initial and long-term results of coronary angioplasty: a report from King
      Chulalongkorn Memorial Hospital.
AB  - PTCA is one of the treatments for coronary heart disease. But in Thailand, there
      is no available data on the long-term outcomes of patients who have undergone
      this procedure. To determine initial and long-term outcomes of patients who
      underwent percutaneous transluminal coronary angioplasty (PTCA), patients who
      underwent PTCA from January 1996 to December 1997 were enrolled. The initial
      results were received from the PTCA registry. The follow-up data were collected
      from medical records, phone calls and mail. Three hundred and forty patients
      (male 68.8%) were enrolled. Mean age was 61.8 +/- 10.1 years. Dyslipidemia was
      the most common risk factor (50.3%), followed by hypertension (44.4%), smoking
      (40%), and diabetes (33.8%). Indications for PTCA were chronic stable angina
      (47.9%), unstable angina (22.1%), acute myocardial infarction (4.3%) and post
      myocardial infarction angina (25.8%). Diseased vessels were left anterior
      descending (44.8%), right coronary artery (28.0%), left circumflex artery
      (25.5%), left main artery (0.9%) and saphenous vein grafts (0.8%). Initial case
      success rate was 93.5 per cent. Stent was implanted in 41.8 per cent of cases. In
      hospital mortality rate was 1.2 per cent. Two patients (0.6%) developed Q-wave
      myocardial infarction (MI). Four patients (1.2%) required emergency bypass
      surgery (CABG). Major adverse cardiac events occurred in 6 patients (1.8%). Two
      hundred ninety one patients (85%) had complete follow-up data, mean follow-up
      time was 990 +/- 326 days. Twenty-one patients died (6.4%) but only 12 (3.5%)
      were cardiac in origin. Other cardiovascular events were non-fatal MI (1.2%),
      unstable angina (10.7%), congestive heart failure (4.6%), and chronic stable
      angina (41.1%). Target lesion revascularization by PTCA was done in 55 patients
      (16.9%) and CABG was performed in 22 patients (6.7%) CONCLUSION: PTCA can be
      performed with a high success rate and low in-hospital complications. Long-term
      outcomes are acceptable and comparable with Western data.

PMID- 12188454
TI  - The effect of blood on rapid urease test for Helicobacter pylori detection: an in
      vitro study.
AB  - The sensitivity of rapid urease test (RUT) for detecting Helicobacter pylori (H.
      pylori) is limited in patients presented with bleeding peptic ulcers. Blood
      contents are potentially responsible for the lack of sensitivity of RUT in
      patients with upper gastrointestinal bleeding. This study was designed to
      determine the efficacy of RUT in detecting H. pylori when exposed to the
      patients' own blood at varying durations. Four gastric antral biopsy specimens
      were collected from dyspeptic patients who underwent gastroscopic examination.
      The first specimen was immediately placed into the urea broth as the control
      group. The second, third and fourth specimens were immersed in the patients' own
      blood for one, two and four hours respectively before testing for the RUT. The
      results of these RUT were compared to those of the control group. Gastric antral
      biopsy specimens tested with the RUT of twenty patients were evaluated in this
      study. The 1-hour RUT and 2-hour RUT was not significantly different in
      sensitivity (92.31% vs 100%: p>0.05, 84.62% vs 100%: p>0.05 respectively) and
      accuracy (95.0% vs 100%: p>0.05, 90.0% vs 100%: p>0.05 respectively) compared to
      the unexposed blood RUT for H. pylori diagnosis. However, the study demonstrated
      that the 4-hour RUT had significantly lower sensitivity (53.85% vs 100%: p<0.05)
      and accuracy (70.00% vs 100%: p<0.05) than that of the unexposed blood RUT for H.
      pylori diagnosis. It is concluded that exposure of gastric biopsy specimens to
      their own blood for four hours significantly decreased the sensitivity of the
      biopsy rapid urease test for H. pylori detection.

PMID- 12188455
TI  - Gastric juice urease test and brushing urease test for Helicobacter pylori
      detection.
AB  - The aim of the study was to demonstrate the sensitivity, specificity and accuracy
      of gastric juice urease test and brushing-urease test compared to the biopsy
      urease test for Helicobacter pylori (H. pylori) detection. For each patient, two
      milliliters of gastric juice was collected and one milliliter in the supernatant
      was tested for rapid urease reactions. One gastric mucus brushing and two
      biopsies were taken from the body and the antrum. The brushing specimens were
      tested for rapid urease reaction by shaking the brush into the urea broth. The
      gold standards for diagnosing of H. pylori are positive H. pylori upon specimen
      culture or positive identification of H. pylori from polymerase chain reaction
      (PCR) assay using primer for vac A gene. Forty patients were enrolled in the
      study including ten patients with gastric ulcer, six patients with duodenal ulcer
      and twenty four patients with non-ulcer dyspepsia. Brushing-urease test and
      biopsy-urease test were not different sensitivity (87.50% vs 93.20%), specificity
      (100% vs 100%) and accuracy (90.25% vs 95.50%). The gastric juice urease test had
      a sensitivity of 65.25 per cent, specificity of 100 per cent and accuracy of 75
      per cent for detecting of H. pylori infection. In conclusion, gastric juice
      urease test had low sensitivity in the diagnosis of H. pylori infection. Brushing
      urease test is as accurate as biopsy-urease test in detecting H. pylori
      infection. However, the brushing method had lower gastric tissue injury than the
      biopsy and so should be used for detecting H. pylori infection in patients with
      coagulopathy.

PMID- 12188457
TI  - A retrospective study of colorectal cancer patients in King Chulalongkorn
      Memorial Hospital.
AB  - To determine the basic clinical information of colorectal cancer in Thailand, the
      authors retrospectively reviewed the medical records and pathological reports of
      293 patients with histologically proven colonic cancer but only 137 patients met
      the inclusion criteria in King Chulalongkorn Memorial Hospital during the three
      year period from July 1997 to June 2000. There were 72 males (53%) and 65 females
      (47%) with an age ranging from 24 to 90 years (mean age 61.2 years). Among these,
      115 patients (83.9%) were older than 50 years. Bowel-habit change, weight loss
      and mucous bloody diarrhea were the most common presentations respectively.
      Distal colorectal cancer is the most common site of colonic cancer (71.3%) and
      28.7 per cent were at the proximal colon. Dukes' D (35%) was the most common
      colorectal cancer staging in the hospital. Considering the sites of metastases,
      liver was the most common site of metastases (61%). The most common cell type was
      moderately-differentiated adenocarcinoma. Low anterior resection was the most
      common surgical procedure (24.9%) since the tumor was usually located distally.
      In conclusion, 1) bowel habit change was the most common presentation for
      colorectal cancer at the hospital and the majority of patients were elderly. 2)
      Colorectal cancer was usually found at the late stage which was associated with
      poor prognosis.

PMID- 12188456
TI  - Inhibitory effect of Lactobacillus acidophilus on Helicobacter pylori in peptic
      ulcer patients: in vitro study.
AB  - Lactobacillus acidophilus (L. acidophilus) have been introduced into many
      fermented dairy products. The presence of L. acidophilus appears to decrease
      Helicobacter pylori (H. pylori) density in the human stomach and could enhance
      antibiotic therapy for H. pylori eradication. This study was designed to
      determine the optimal density of L. acidophilus that has a maximum inhibitory
      effect on H. pylori in peptic ulcer patients. To determine whether L. acidophilus
      has an inhibitory effect on H. pylori isolated from peptic ulcer patients and to
      determine whether the optimal density of L. acidophilus has a maximum inhibitory
      effect on H. pylori isolated from peptic ulcer patients. H. pylori was isolated
      from gastric biopsy specimens of peptic ulcer patients. The suspension of pure H.
      pylori colonies were inoculated into the broth and adjusted to match the density
      of No.3 MacFarland standard (approximately 9x10(8) cells/ml). Forty microliters
      of the suspension were equally spread onto each quadrant of the plate and left to
      dry. L. acidophilus was prepared from LC-1 (Nestle Research Center, Switzerland).
      They were grown on blood agar and incubated overnight at 37 degrees C. The
      suspension of L. acidophilus was inoculated into the broth and adjusted to match
      the density of No.1, No.2, No.3 and No.4 MacFarland standard (approximately
      3x10(8), 6x10(8), 9x10(8) and 12x10(8) cells/ml respectively). Ten microliters of
      each density of L. acidophilus was dropped onto each quadrant of a previously
      inoculated H. pylori plate and then the plate was kept under microaerophilic
      conditions for 72 hours. Inhibition clear halo zone of H. pylori around the
      colonies of L. acidophilus was interpreted as the inhibitory effect. H. pylori
      were isolated from gastric biopsy specimens of fifteen peptic ulcer patients
      (eleven patients with gastric ulcer and four patients with duodenal ulcer). A
      total of sixty tests of inhibitory effect of L. acidophilus on H. pylori were
      evaluated in the present study. L. acidophilus had inhibitory effect on H. pylori
      in 13/15 patients (86.67%) and L. acidophilus in the density of No.3 MacFarland
      standard had a significantly higher inhibitory effect on H. pylori in the density
      of No.3 MacFarland than that of No.1 (60% vs 20%; p<0.05), No.2 (60% vs 20%;
      p<0.05) and No.4 (60% vs 20%; p<0.05) MacFarland standard. In conclusion, L.
      acidophilus has an inhibitory effect on H. pylori isolated from peptic ulcer
      patients. Approximately an equal density of L. acidophilus on H. pylori has the
      most favorable effect. This optimal density of L. acidophilus should have maximum
      effect on H. pylori clearance and could enhance antibiotic therapy for H. pylori
      eradication in humans.

PMID- 12188458
TI  - Cost-effective study of determination methods for low-density lipoprotein by new
      direct assay compared to Friedewald's formula calculation in hypercholesterolemic
      subjects.
AB  - OBJECTIVE: To study the cost effectiveness of determination methods for low
      density lipoprotein by new direct assay compared to Friedewald's formula
      calculation. DESIGN: descriptive study. MATERIAL: Fasting serum from 100 subjects
      with a history of hypercholesterolemia. METHOD: Specimens were determined for
      total cholesterol, high-density lipoprotein (HDL) and triglyceride using
      automated clinical chemistry, as the basic information in calculation of LDL
      level. Each specimen was also processed by direct LDL assay by the same
      automation. Correlation of the results from both methods was analyzed. Cost
      effectiveness analysis was then performed. RESULTS: The least-squares equation
      from comparing direct LDL assay to calculation method gave Y = 0.897X + 20.42 (r
      = 0.996, p < 0.05). According to the present study, the cost per utility of the
      direct assay method (47.54 baht) was more expensive than the calculation method
      (29.59 baht). CONCLUSION: The results from both methods were well related.
      However, the cost per utility of the calculation method is cheaper, therefore,
      the authors recommend the use of the calculation method rather than the direct
      assay for follow-up of LDL level in hypercholesterolemic patients.

PMID- 12188459
TI  - Duodenal Helicobacter pylori associated duodenal ulcer depend on gastric
      Helicobacter pylori status.
AB  - Gastric Helicobacter pylori (H. pylon) plays an important role in the
      pathogenesis of duodenal ulcer (DU), although not all H. pylori infected persons
      will develop disease. Duodenal H. pylori was supposed to be one of the factors
      related with DU. The aim of this study was to investigate whether H. pylori in
      the duodenum of patients with DU plays a critical role in the pathogenesis of DU
      regarding the gastric H. pylori status. Furthermore, it was to determine the
      prevalence of duodenal H. pylori infection in Thailand. Ninety three patients
      were included in the study. They underwent gastroscopic evaluation for dyspeptic
      symptoms and none of them had previous H. pylori eradication therapy. An upper
      gastrointestinal endoscopy was performed and two specimens were collected each
      form the antrum, midcorpus and duodenal bulb in order to diagnose H. pylori
      infection. The gold standard for H. pylori detection is a positive specimen
      culture or polymerase chain reaction (PCR) assay for the vac A gene or positive
      urease test plus H. pylori seen in the pathology. Ninety three dyspeptic patients
      (43 males and 50 females; mean age 48.2 years; range 22 to 79 years) were
      included in the study. Duodenal H. pylori was detected in 31/93 (33.33%) patients
      which included 15 (48.38%) patients with duodenal ulcer, 2 (6.45%) patients with
      gastric ulcer and 14 (45.16%) patients with NUD. Five of thirty one (16.21%)
      patients with duodenal H. pylori infection had negative gastric H. pylori. These
      five patients included 1 with DU, 1 with DU and 3 with NUD. Duodenal H. pylori
      was associated with DU dependent of the presence of gastric H. pylori (p<0.05)
      and there was no association between duodenal H. pylori with negative gastric H.
      pylori and duodenal ulcer (p>0.05). Duodenal H. pylori is associated with
      duodenal ulcer dependent on the presence of gastric H. pylori. These results
      suggest that transmission of gastric H. pylori to the duodenum was prerequisited
      for the formation of DU.

PMID- 12188460
TI  - Euthanasia, assisted suicide, and cessation of life support: Japan's policy, law,
      and an analysis of whistle blowing in two recent mercy killing cases.
AB  - Issues pertaining to euthanasia, assisted suicide, and cessation of life support
      continue to be a subject of worldwide interest. Euthanasia- particularly "active"
      euthanasia- is not considered legally or socially acceptable in most countries.
      In Japan, the first judgment of a case involving euthanasia took place in 1949.
      Since then there have been another five cases that reached the point of
      sentencing in 1990. All six cases were examples of so called "active euthanasia",
      in which the termination of life was performed by family members. However, the
      focus of discussion has been changed dramatically in recent years, owing to two
      prominent cases of mercy killing in 1995 (Yokohama) and 1996 (Kyoto),
      respectively. Medical doctors were involved in both of these cases, and
      euthanasia moved from being a theoretical problem to a practical dilemma. These
      cases also drew attention to the fact that assisted suicide could be
      distinguished from euthanasia. The first part of this paper will summarize the
      current status of euthanasia and the cessation of life support in Japan, focusing
      on its historical background and policy. The second part will briefly sketch the
      characteristics of Japanese law and then will examine the two recent cases of
      mercy killing mentioned above to try and determine the roles of whistle blowing
      in the medical practice arena, with particular reference to Japanese culture.
      This analysis is a challenge to elucidate how ethics and the law interact, and
      influence medical practice in a specific cultural context.

PMID- 12188461
TI  - Women's perceptions of iron deficiency and anemia prevention and control in eight
      developing countries.
AB  - The World Health Organization estimates that 58% of pregnant women in developing
      countries are anemic. In spite of the fact that most ministries of health in
      developing countries have policies to provide pregnant women with iron in a
      supplement form, maternal anemia prevalence has not declined significantly where
      large-scale programs have been evaluated. During the period 1991-98, the
      MotherCare Project and its partners conducted qualitative research to determine
      the major barriers and facilitators of iron supplementation programs for pregnant
      women in eight developing countries. Research results were used to develop pilot
      program strategies and interventions to reduce maternal anemia. Across-region
      results were examined and some differences were found but the similarity in the
      way women view anemia and react to taking iron tablets was more striking than
      differences encountered by region, country or ethnic group. While women
      frequently recognize symptoms of anemia, they do not know the clinical term for
      anemia. Half of women in all countries consider these symptoms to be a priority
      health concern that requires action and half do not. Those women who visit
      prenatal health services are often familiar with iron supplements, but commonly
      do not know why they are prescribed. Contrary to the belief that women stop
      taking iron tablets mainly due to negative side effects, only about one-third of
      women reported that they experienced negative side effects in these studies.
      During iron supplementation trials in five of the countries, only about one-tenth
      of the women stopped taking the tablets due to side effects. The major barrier to
      effective supplementation programs is inadequate supply. Additional barriers
      include inadequate counseling and distribution of iron tablets, difficult access
      and poor utilization of prenatal health care services, beliefs against consuming
      medications during pregnancy, and in most countries, fears that taking too much
      iron may cause too much blood or a big baby, making delivery more difficult.
      Facilitators include women's recognition of improved physical well being with the
      alleviation of symptoms of anemia, particularly fatigue, a better appetite,
      increased appreciation of benefits for the fetus, and subsequent increased demand
      for prevention and treatment of iron deficiency and anemia.

PMID- 12188462
TI  - What is a 'planned' pregnancy? Empirical data from a British study.
AB  - The terms "planned", "unplanned", "intended", "unintended", "wanted" and
      "unwanted" are often used in relation to pregnancy in health policy, health
      services and health research. This paper describes the findings relating to
      women's understanding of these terms from the qualitative stage of a British
      study. We found that when discussing the circumstances of their pregnancies,
      women tended not to use the above terms spontaneously. When asked to explain the
      terms, women were able to do so but there was considerable variation in
      understanding. Most, but not all, were able to apply the terms. Women applied the
      term "planned" only if they had met four key criteria. Intending to become
      pregnant and stopping contraception were not sufficient criteria, in themselves,
      to apply the term; partner agreement and reaching the right time in terms of
      lifestyle/life stage were also necessary. In contrast, "unplanned" was a widely
      applied term and covered a variety of circumstances of pregnancy. The other terms
      were less favoured, "unwanted" being positively disliked. We recommend that
      survey questions eliciting information on women's circumstances of pregnancy do
      not rely on the above terms in isolation and, further, that a more circumspect
      use of the terms in policy and clinical settings is required.

PMID- 12188463
TI  - Watching the clock: keeping time during pregnancy, birth, and postpartum
      experiences.
AB  - In this paper, I analyze how different didactic discourses surrounding pregnancy,
      birth, and postpartum care portray time in procreative events. I investigate
      advice regarding procreative experiences offered to women by a variety of
      ''experts", and offered by experts to each other, examining literature which
      demonstrates the wide range of didactic approaches to procreative events that are
      accessible in US culture, from masculinist medical orthodoxy--the dominant
      perspective--to the naturalist/feminist midwifery model, with self-help
      literature reflecting the influence of both ends of this spectrum as well as of
      consumer-oriented health activism. I explore how the conceptualization of time in
      the medical discourse contributes to the overpowering or disempowering of
      procreating women, and how the self-help and midwifery approaches respond to the
      medical model--ranging on a continuum from reification to refutation. Obstetrics
      works on women's bodies to make them stay on time and on course; this quest
      becomes more obsessively time-focused over time. In contrast, the midwifery
      discourse centers on women active in time, rather than against it. Self-help book
      authors line up somewhere in the middle, mostly taking medical management of
      procreative time for granted and occasionally try to show women ways in which we
      can buy time or bide our time against medicine.

PMID- 12188464
TI  - Understanding household demand for indoor air pollution control in developing
      countries.
AB  - More than 2 billion people rely on solid fuels and traditional stoves or open
      fires for cooking, lighting, and/or heating. Exposure to emissions caused by
      burning these fuels is believed to be responsible for a significant share of the
      global burden of disease. To achieve widespread health improvements,
      interventions that reduce exposures to indoor air pollution will need to be
      adopted and consistently used by large numbers of households in the developing
      world. Given that such interventions remain to be adopted by large numbers of
      these households, much remains to be learned about household demand for
      interventions designed (in part at least) to reduce indoor air pollution. A
      general household framework is developed that identifies in detail the
      determinants of household demand for indoor air pollution interventions, where
      demand for an intervention is expressed in terms of willingness to pay. Household
      demand is shown to be a combination of three terms: (1) the direct consumption
      effect; (2) the child health effect; and (3) the adult health effect. While micro
      level data are not available to estimate directly this model, existing data and
      information are used to estimate just the health effects component of household
      demand. Based on such existing information, it might be concluded that household
      demand should seemingly be strong given that willingness to pay, based on
      existing information, is seemingly large compared to costs for common
      interventions like improved stoves. Given that household demand is not strong for
      existing interventions, this analysis shows that more clearly focused research on
      household demand for interventions is needed if such interventions are going to
      be demanded (i.e. adopted and used) by large numbers of households throughout the
      developing world. Four priority areas for future research are: (1) improving
      information on dose-response relationships between indoor air pollution and
      various health effects (e.g. increased mortality and morbidity risks); (2)
      improving information on impacts from interventions in terms of air pollution
      reductions and also cooking times, fuel use, and heat intensities; (3) improving
      information on household shadow values for improved health, with separate
      information for adult and child health; and (4) considering more directly
      household information, and its adequacy, for their ability to evaluate the
      relationships between fuel use and health.

PMID- 12188465
TI  - Polygyny, maternal HIV status and child survival: Rakai, Uganda.
AB  - The objective of this research was to assess the association of child mortality
      with polygyny and maternal HIV status through a prospective community-based study
      in Rakai district, Uganda. We sought to test whether there was an indirect
      evidence that polygynous households in an HIV prevalent area may divert resources
      away from the children of HIV-infected mothers in favor of children with better
      survival prospects. We test this theory using data from a follow-up study which
      collected detailed behavioral and medical information at 10-month intervals on a
      cohort of over 4000 pregnant women and their infants (5300 person years of
      observation). Cox proportional hazards models estimated the mortality hazard (RR)
      associated with polygyny for children of HIV-negative and HIV-positive mothers.
      HIV prevalence in the full cohort of mothers was 11.9%, and 23% of mothers lived
      in polygynous households. Multivariate analysis showed an increased hazard of
      child mortality if the mother was HIV-positive (RR = 1.75, p<0.001). Maternal
      education reduced mortality, whereas low birth weight increased mortality risk.
      Polygyny was associated with an increase in the hazard of child mortality in the
      full sample (RR = 1.36, p<0.001) and in mothers who were HIV-positive (RR = 2.17,
      p<0.001), but not in HIV-negative mothers. Being born to an HIV-positive mother
      increased mortality risk and polygyny accentuated a child's risk of death.
      Polygyny had no significant effect on the survival of children with HIV-negative
      mothers. Polygynous households, where not all wives may have HIV, could be
      diverting resources away from the children of the infected wives.

PMID- 12188466
TI  - Why is less money spent on health care for the elderly than for the rest of the
      population? Health care rationing in German hospitals.
AB  - The consequences of population ageing for the public health care system and
      health care costs may be less severe than is commonly assumed. Hospital discharge
      data from Germany's largest health insurer (AOK) show that the cost of caring for
      patients during their last year of life makes up a large part of total health
      expenditures. And this last year of life is less costly if patients die at an
      advanced age. As a multivariate analysis reveals, oldest old patients as a rule
      receive less costly treatment than younger patients for the same illness.
      Moreover, this pattern is more pronounced for elderly women than for elderly men.
      These findings suggest that health care is informally rationed according to the
      age and sex of the patient. The data also indicate that there may be more age
      related rationing going on in Germany than in the United States. Future research
      should investigate the national, institutional, and individual factors behind
      health care rationing. In this paper, I discuss the physician's professional
      decision as one plausible determinant.

PMID- 12188467
TI  - Analysing changes of health inequalities in the Nordic welfare states.
AB  - This study examined changes over time in relative health inequalities among men
      and women in four Nordic countries, Denmark, Finland, Norway and Sweden. A
      serious economic recession burst out in the early 1990s particularly in Finland
      and Sweden. We ask whether this adverse social structural'development influenced
      health inequalities by employment status and educational attainment, i.e. whether
      the trends in health inequalities were similar or dissimilar between the Nordic
      countries. The data derived from comparable interview surveys carried out in
      1986/87 and 1994/95 in the four countries. Limiting long-standing illness and
      perceived health were analysed by age, gender, employment status and educational
      attainment. First, age-adjusted overall prevalence percentages were calculated.
      Second, changes in the magnitude of relative health inequalities were studied
      using logistic regression analysis. Within each country the prevalence of ill
      health remained at a similar level, with Finns having the poorest health.
      Analysing all countries together health inequalities by employment status and
      education showed no major changes. There were slightly different tendencies among
      men and women in inequalities by both health indicators, although these did not
      reach statistical significance. Among men there was a suggestion of narrowing
      health inequalities, whereas among women such a suggestion could not be
      discerned. Looking at particular countries some small changes in men's as well as
      women's health inequalities could be found. Over a period of deep economic
      recession and a large increase in unemployment, particularly in Finland and
      Sweden, health inequalities by employment status and education remained broadly
      unchanged in all Nordic countries. Thus, during this fairly short period health
      inequalities in these countries were not strongly influenced by changes in other
      structural inequalities, in particular labour market inequalities. Institutional
      arrangements in the Nordic welfare states, including social benefits and
      services, were cut during the recession but nevertheless broadly remained, and
      are likely to have buffered against the structural pressures towards widening
      health inequalities.

PMID- 12188468
TI  - Impact of improvement of water supply on household economy in a squatter area of
      Manila.
AB  - To estimate the impact of the improvement of water supply. a comparative study on
      water collection and household expenditure on water was conducted between a
      former squatter community with an improved water supply (Leveriza: LE) and a
      typical squatter community with public water faucets (Maestranza: MA) in Manila,
      the Philippines. Data were collected from 201 structured household interviews and
      a focus group discussion among housewives in each community. To measure the time
      spent collecting water, observations of private and public water faucets were
      conducted. The residents in LE enjoyed significantly larger quantities of water
      from private water connections than in MA, where only three public water faucets
      were available as a water source. Conversely, the unit price of water in LE was
      much lower than in MA. In LE, 72.1% of the households started working for more
      income using time saved through the improvement of water supply and the
      proportion of the households under the poverty threshold was reduced from 55.6%
      to 29.9%. In MA, 68.6% of the households expressed their willingness to work for
      more income when time spent collecting water was saved. It would be possible for
      MA to reduce the proportion of the households under the poverty threshold through
      the improvement of the water supply. The results of the study indicated that the
      improvement of water supply would possibly encourage urban slum residents to
      increase their household incomes through reallocating time saved to income
      generating activities. The underserved residents spent more money for less water
      compared to those with access to private water connections. In MA, it took 3-4 h,
      on average, to complete one water collecting task, even though the nearest public
      water faucet was within 100 m of any housing unit. This suggests that the
      definition of accessibility to safe water be reconsidered when discussing the
      urban poor.

PMID- 12188469
TI  - Ethnic identities, social capital and health inequalities: factors shaping
      African-Caribbean participation in local community networks in the UK.
AB  - This paper examines the impact of ethnic identity on the likelihood of peoples'
      participation in local community networks, in the context of recent policy
      emphasis on the participation of marginalised communities in such networks as a
      means of reducing health inequalities. Conceptually, the paper is located against
      the background of debates about possible links between health and social capital-
      defined in terms of grassroots participation in local community networks--and an
      interest in the way in which social exclusion impacts on social capital. The
      paper draws on lengthy semi-structured, open-ended interviews with 25 African
      Caribbean residents of a deprived multi-ethnic area of a south England town.
      While African-Caribbean identity played a central role in peoples' participation
      in inter-personal networks, this inter-personal solidarity did not serve to unite
      people at the local community level beyond particular face-to-face networks.
      Levels of participation in voluntary organisations and community activist
      networks were low. Informants regarded this lack of African-Caribbean unity
      within the local community as a problem, saying that it placed African-Caribbean
      people at a distinct disadvantage--furthering their social exclusion through
      limiting their access to various local community resources. The paper examines
      the way in which the construction of ethnic identities--within a context of
      institutionalised racism at both the material and symbolic levels--makes it
      unlikely that people will view local community organisations or networks as
      representative of their interests or needs, or be motivated to participate in
      them. Our findings highlight the limitations of policies which simply call for
      increased community participation by socially excluded groups, in the absence of
      specific measures to address the obstacles that stand in the way of such
      participation.

PMID- 12188470
TI  - The impact of the 9-21 earthquake experiences of Taiwanese nurses as rescuers.
AB  - The powerful earthquake of September 21, 1999 wrought incalculable havoc on lives
      and properties in Taiwan. Although the scars of the earthquake can never be
      erased, the calamity can lead to a more full understanding of the experiences,
      perceptions and reflections of nurses involved directly in post-rescue
      situations. The purpose of this study was to compare the impacts of rescue
      experiences on Taiwanese female and male nurses who worked as rescuers following
      the earthquake of 21 September. A purposive sample of 46 nurses (40 women, 6 men)
      (mean age 26) who worked in a renowned hospital with a reputation for high
      quality of emergency care in Northern Taiwan was obtained. Data were collected by
      in-depth semi-structured interviews and analyzed by a unique mode of between
      method triangulation. The majority of the subjects (38 female, 6 male) reported
      various impacts from their rescue experiences. They are: (a) recognition of the
      impermanence of life and wishing to lead a more significant life (32 female, 3
      male); (b) more caring relationships with others and for their homeland (19
      female, 5 male); (c) a clearer concept of disaster care (19 female, 4 male); (d)
      a better appreciation of the value of nursing and their own self-worth (11
      female, 3 male); (e) enhanced knowledge of the survivors' needs (3 female); and
      (f) enhanced ability to identify the factors hindering rescue operations (1
      female, 2 male). However, one female nurse complained of having been bothered by
      feelings of fear of earthquake disasters resulting from her rescue experience.
      Rescue experiences help to strengthen most Taiwanese nurses' professional
      competency, reinforce their commitment to nursing, and lead them to have positive
      life goals. The relative weight of the impacts for male and female nurses were
      somewhat different. The vulnerability of nurses, which was manifested in the post
      rescue stage, requires attention and long-term follow-up. A comprehensive and
      organized pre-rescue training program which recognizes the need to care for both
      acute and chronic post-disaster conditions, along with spiritual care for the
      survivors, as well as a "disaster reduction" course for health professionals are
      suggested.

PMID- 12188471
TI  - Cohabitation and marital status as predictors of mortality--an eight year follow
      up study.
AB  - In a follow-up study of 1265 women and men aged 50, 60 and 70 years, we analysed
      how mortality was associated with cohabitation status (living alone/not living
      alone), living with/without a partner, and marital status respectively. Data
      originate from a longitudinal questionnaire study of a random sample of people
      born in 1920, 1930 and 1940 with baseline in 1990. Survival time for all
      individuals were established during the next 8 years until May 1998. Multivariate
      Cox analysis stratified by age and gender showed that individuals living alone
      experienced a significantly increased mortality compared to individuals living
      with somebody HR = 1.42(1.04-1.95) adjusted for functional ability, self-rated
      health, having children, smoking, diet and physical activity. Similar analyses
      were performed for the variable living with/without a partner HR = 1.38(1.01
      1.88) and marital status HR = 1.25(0.93-1.69), adjusted for the same covariates.
      Inclusion of the health behaviour variables--smoking, diet and physical activity-
      one by one to a model with functional ability, self-rated health and one of the
      three determinants (cohabitation status, living with/without partner, marital
      status) showed no effect on the association with mortality. Hereby, we found no
      evidence of an indirect effect of health behaviours on the association between
      living arrangements and mortality. In contrast to many previous studies, we found
      no significant gender and age differences in the association between living
      arrangement and mortality. We suggest that in future studies of social relations
      and mortality, cohabitation status is considered to replace marital status as
      this variable may account for more of the variation in mortality.

PMID- 12188472
TI  - Smoking and young women in Vietnam: the influence of normative gender roles.
AB  - Smoking in Vietnam, as elsewhere in Asia, is strongly sex-linked. A 1997 national
      prevalence survey found about half of males but just 3.4% of females used tobacco
      regularly. Little is known about smoking-related health awareness or attitudes in
      Vietnam. There is concern that women may take up smoking if rapid social change
      brings alteration in traditional gender norms that discourage this behaviour.
      Effective tobacco control depends upon accurate understanding of prevailing
      knowledge and views. This paper reports on a 1999-2000 collaborative study into
      smoking attitudes, practices and health awareness, with particular reference to
      gender norms. A survey, based partly on findings from initial focus groups, was
      administered to young female students (n = 1018) and factory workers (n = 1002)
      in Ho Chi Minh City, Vietnam's largest metropolis. Participants were recruited
      through random cluster sampling. Results indicated that smoking continues to be
      shunned by the vast majority of young urban students and factory workers,
      although prevalence was slightly higher than found in national surveys, and there
      was a moderate degree of experimentation. Perhaps of greater concern was the
      degree of ambivalence voiced about taking up smoking in the future. Moreover,
      while nearly all expressed awareness of negative health effects of tobacco, these
      were vaguely worded and excluded key mortality risks. Gender norms appeared to be
      strongly enduring, with female non-smoking attributed overwhelmingly to its
      'inappropriateness'. Male smoking was seen as normative. Overall, workers
      (representing a low-income, less-educated population) had higher rates of tobacco
      use and less health knowledge than students. The paper concludes with a
      discussion about ramifications for public health interventions.

PMID- 12188473
TI  - Early training in orthopaedic surgery.

PMID- 12188474
TI  - The trauma centre: now and in the future.

PMID- 12188475
TI  - Catastrophic failure of the Elite Plus total hip replacement, with a Hylamer
      acetabulum and Zirconia ceramic femoral head.
AB  - We report catastrophic early failure of a cemented total hip replacement
      comprising a modular femoral component with a Zirconia ceramic head and an
      acetabular component of cross-linked ultra-high molecular-weight polyethylene
      (Hylamer). Between 1995 and 1999 we implanted 29 hips in 26 patients with a mean
      age of 49.2 years. Survivorship analysis in this group revealed a failure rate of
      67.6% at five years. All hips which failed did so because of aseptic loosening
      with progressive osteolysis or radiolucencies. We therefore recommend early and
      regular review of all patients with this combination of implants and early
      revision surgery in order to avoid massive bone loss.

PMID- 12188476
TI  - The long-term outcome of primary osteochondritis of the hip (Legg-Calve-Perthes'
      disease).
AB  - We have previously reported on 57 patients (60 hips) with a past history of Legg
      Calve-Perthes' disease at a mean of 34 years after the onset of symptoms. From
      this original group, 48 patients (51 hips) were also available for review after a
      mean of 50.2 years. We consider that the best prognostic indicator for the hip is
      the shape of the femoral head at skeletal maturity. Normal or flattened spherical
      heads present few problems. Irregular or very irregular heads are associated with
      a poor outcome.

PMID- 12188477
TI  - Failure of hydroxyapatite-coated acetabular cups. Ten-year follow-up of 85 Landos
      Atoll arthroplasties.
AB  - Between March 1990 and May 1991 we performed 85 primary total hip replacements in
      74 patients using the Landos Atoll hydroxyapatite (HA)-coated cup and the Corail
      HA-coated stem. The patients were followed up for a mean of ten years. Of the 85
      cups, 26 (31%) have already been revised and a further six are radiologically
      unstable and awaiting revision. Two femoral stems have been revised for infection
      without loosening. The retrieved acetabular cups were studied by SEM and image
      processing techniques to quantify the amount of residual HA on the cup. This was
      correlated with the clinical variables and modes of failure. The residual HA (as
      a percentage of the surface) on the loose cups correlated negatively with the
      duration of implantation (r = -0.732, p < 0.001). Six cups were stable at
      revision and had more residual HA coating than those which were loose (p < 0.01).
      The rate of failure of the Landos Atoll HA-coated, smooth hemispherical cup with
      screw fixation is unacceptably high. Resorption of the HA coating is markedly
      increased in loose cups compared with stable cups. HA coating cannot substitute
      for stable mechanical fixation.

PMID- 12188478
TI  - The modified Spitzy shelf operation for patients with dysplasia of the hip. A 24
      year follow-up study.
AB  - We evaluated the long-term results of a modified Spitzy shelf operation for
      secondary osteoarthritis in 119 hips with a mean follow-up of 23.8 years. The
      mean age of the patients at the time of surgery was 25 years. Preoperative
      osteoarthritic change, the age at operation and shelf height were important
      factors in determining the outcome. Of the 61 hips in the pre-stage (three) and
      the initial stage (58) of osteoarthritis, 53 (87%) had good results, compared
      with only 30 (51%) of 58 hips with advanced osteoarthritis. Of the latter, 72% of
      those aged less than 25 years had good results compared with only 40% of patients
      aged over 25 years. The shelf height in the group with good results was
      significantly lower than in those with poor results. This operation is a safe
      procedure and indicated for acetabular dysplasia or subluxation of the hip with
      early osteoarthritic change in patients aged less than 25 years.

PMID- 12188479
TI  - Dislocation of the bearing of the Oxford lateral unicompartmental arthroplasty. A
      radiological assessment.
AB  - When the Oxford unicompartmental meniscal bearing arthroplasty is used in the
      lateral compartment of the knee, 10% of the bearings dislocate. A radiological
      review was carried out to establish if dislocation was related to surgical
      technique. The postoperative radiographs of 46 lateral unicompartmental
      arthroplasties were analysed. Five variables which related to the position and
      alignment of the components were measured. Dislocations occurred in six knees.
      Only one of the five variables, the proximal tibial varus angle, had a
      statistically significant relationship to dislocation. This variable quantifies
      the height of the lateral joint line. The mean proximal tibial varus angle for
      knees the bearings of which had dislocated was 9 degrees and for those which had
      not it was 5 degrees. In both groups it was greater than would be expected in the
      normal knee (3 degrees). Our study suggests that a high proximal tibial varus
      angle is associated with dislocation. The surgical technique should be modified
      to account for this, with care being taken to avoid damage to or overdistraction
      of the lateral soft tissues.

PMID- 12188480
TI  - A randomised, controlled trial of cemented versus cementless press-fit condylar
      total knee replacement. Ten-year survival analysis.
AB  - We have carried out a long-term survival analysis of a prospective, randomised
      trial comparing cemented with cementless fixation of press-fit condylar primary
      total knee replacements. A consecutive series of 501 replacements received either
      cemented (219 patients, 277 implants) or cementless (177 patients, 224 implants)
      fixation. The patients were contacted at a mean follow-up of 7.4 years (2.7 to
      13.0) to establish the rate of survival of the implant. The ten-year survival was
      compared using life-table and Cox's proportional hazard analysis. No patient was
      lost to follow-up. The survival at ten years was 95.3% (95% CI 90.3 to 97.8) and
      95.6% (95% CI 89.5 to 98.2) in the cemented and cementless groups, respectively.
      The hazard ratio for failure in cemented compared with cementless prostheses was
      0.97 (95% CI 0.36 to 2.6). A comparison of the clinical outcome at ten years in
      80 knees showed no difference between the two groups. The survival of the press
      fit condylar total knee replacement at ten years is good irrespective of the
      method of fixation and brings into question the use of more expensive cementless
      implants.

PMID- 12188481
TI  - A comparative study of the medial St Georg sled and kinematic total knee
      arthroplasties. Ten-year survivorship.
AB  - We have studied the long-term outcome of 408 primary medial St Georg Sled
      unicompartmental arthroplasties of the knee and 531 primary Kinematic total knee
      arthroplasties using survivorship analysis. The operations were performed by a
      number of surgeons under the supervision of two consultants at one orthopaedic
      centre. Prospective clinical assessment was carried out before and at 2, 5, 8,
      10, 12 and 15 years after operation. Failure was defined as follows: revision or
      removal of the implant; the presence of moderate or severe pain; or 'worst-case'
      with all patients lost to follow-up. Cumulative survival rates at ten years were
      calculated using life tables. The follow-up rate was 97%. At ten years, 25 medial
      sled arthroplasties and 20 Kinematic knee arthroplasties had been revised. With
      revision or removal as the survivorship endpoint at ten years there was a success
      rate of 87.5% for the medial sled and 89.6% for the Kinematic knee arthroplasty.
      When moderate or severe pain was included these rates became 79.4% for both
      arthroplasties. There was no statistically significant (p > 0.05) difference
      between the rates of survival for the two arthroplasties using either of the
      endpoint criteria. Good or excellent results were recorded for 77.9% of the
      medial sled knees and 75.1% for the Kinematic knees. The former had 93.8% of
      cases with a final range of movement in excess of 90 degrees compared with 83.7%
      for the Kinematic knees (p < 0.01). We conclude that at a single orthopaedic
      centre in the UK, the St Georg Sled medial compartment arthroplasty for
      appropriate specific indications offers predictable survivorship at ten years
      which is comparable with that of the Kinematic total knee arthroplasty.

PMID- 12188482
TI  - Radial osteotomy for late-stage Kienbock's disease. Wedge osteotomy versus radial
      shortening.
AB  - We have reviewed 20 patients with stage-IIIB and stage-IV Kienbock's disease in
      order to examine the efficacy of two forms of radial osteotomy, namely radial
      wedge osteotomy and radial shortening. Lateral closing wedge osteotomies and
      radial shortenings were carried out on 11 and nine patients, respectively. There
      were no preoperative differences with respect to age, gender, and radiological
      stage. After a mean follow-up of 29 months, all patients, in both groups, had
      either a good or an excellent outcome. After the lateral closing wedge osteotomy,
      the radioscaphoid angle significantly increased and the Stahl index significantly
      decreased. Progression of the degenerative changes at the radioscaphoid joint was
      found in two patients in this group. By contrast, there were no significant
      changes in any radiological parameters after radial shortening. Both procedures
      gave acceptable clinical results in stage-IIIB and stage-IV Kienbock's disease.

PMID- 12188483
TI  - A prospective, randomised study to compare extracorporeal shock-wave therapy and
      injection of steroid for the treatment of tennis elbow.
AB  - We undertook a prospective, randomised study to compare the analgesic effect of
      injection of steroid and of extracorporeal shock-wave therapy (ESWT) for the
      treatment of tennis elbow. Group 1 received a single injection of 20 mg of
      triamcinolone with lignocaine while group 2 received 2000 shock waves in three
      sessions at weekly intervals. After six weeks there was a significant difference
      between the groups with the mean pain score for the injection group falling from
      66 to 21 compared with a decrease from 61 to 35 in the shock-wave group (p =
      0.05). After three months, 84% of patients in group 1 were considered to have had
      successful treatment compared with 60% in group 2. In the medium term local
      injection of steroid is more successful and 100 times less expensive than ESWT in
      the treatment of tennis elbow.

PMID- 12188485
TI  - Rotatory subluxation of the scaphoid in Kienbock's disease is not a cause of
      scapholunate advanced collapse (SLAC) in the wrist.
AB  - We have examined whether the rotatory subluxation of the scaphoid which is seen
      in patients with advanced Kienbock's disease is associated with scapholunate
      advanced collapse (SLAC) wrist. We studied 16 patients (11 men, 5 women) who had
      stage-IV Kienbock's disease with chronic subluxation of the scaphoid. All had
      received conservative treatment. The mean period of affection with Kienbock's
      disease was 30 years (14 to 49). No wrist had SLAC. In eight patients, 24 years
      or more after the onset of the disease, the articular surface of the radius had
      been remodelled by the subluxed scaphoid with maintenance of the joint space. The
      wrists of six patients were considered to be excellent, nine good, and one fair
      according to the clinical criteria of Dornan. Our findings have shown that
      rotatory subluxation of the scaphoid in Kienbock's disease is not a cause of SLAC
      wrist and therefore that scaphotrapeziotrapezoid arthrodesis is not required for
      the management of these patients.

PMID- 12188484
TI  - Deformities of the elbow in achondroplasia.
AB  - Lack of full extension of the elbow is a common abnormality in patients with
      achondroplasia. We studied 23 patients (41 elbows) clinically and radiologically.
      Extension of the elbow was assessed clinically and the angle of posterior bowing
      of the distal humerus was measured from lateral radiographs. There was limited
      extension of the elbow in 28 (68.3%) and the mean loss of extension was 13.1
      degrees. Posterior bowing of the humerus was seen in all elbows with a mean angle
      of 17.0 degrees. There was a positive correlation between these two measurements.
      Posterior bowing greater than 20 degrees caused a loss of full elbow extension.
      Posterior dislocation of the radial head was seen in nine elbows (22.0%). The
      mean loss of extension of the elbows was 28.7 degrees which was significantly
      greater than that of these elbows in which the head was not dislocated (8.7
      degrees), although posterior bowing was not significantly different between these
      two groups (19.3 degrees and 16.3 degrees). Posterior bowing of the distal
      humerus is a principal cause of loss of extension of the elbow. Posterior
      dislocation of the radial head causes further limitation of movement in the more
      severely affected joints.

PMID- 12188486
TI  - The influence of age on outcome after operation for the carpal tunnel syndrome. A
      prospective study.
AB  - Decompression of the carpal tunnel is a common surgical procedure. Although the
      incidence of the carpal tunnel syndrome increases with age, there is no clear
      information available on the outcome of surgery in relation to age. We studied
      prospectively 87 consecutive patients who underwent decompression, using a
      validated self-administered questionnaire, and found that improvement in symptoms
      and function decreased with increasing age. This was most marked in patients over
      the age of sixty years.

PMID- 12188487
TI  - Biaxial total wrist replacement in patients with rheumatoid arthritis. Clinical
      review, survivorship and radiological analysis.
AB  - We have implanted 76 biaxial total wrist prostheses as a primary procedure in
      patients with rheumatoid arthritis of the wrist. A total of 66 was reviewed at a
      mean follow-up time of 52 months. Pain was relieved in 67% of the surviving wrist
      replacements. On the basis of the Hospital for Special Surgery scoring system, 49
      wrists (74%) were graded as fair to excellent. More than half of the 27 patients
      who had an arthrodesis on the contralateral wrist would have preferred a second
      arthroplasty. Five replacements were revised or fused because of loosening and a
      further nine showed signs of radiological loosening, three of which were
      asymptomatic. The probability of survival of the biaxial total wrist replacement
      at eight years was 83% with revision surgery as the terminal event, 78% with
      radiological loosening as the endpoint and 82% with dorsal migration and
      displacement from the metacarpal as the terminal event. There was a linear
      relationship between subsidence of the component and distal loosening. There was
      no evidence that the length of the stem of the carpal component, within the third
      metacarpal, affected any of the terminal events. The position and alignment of
      the carpal component within the bone at the time of surgery significantly affect
      the outcome and can be used to predict failure.

PMID- 12188488
TI  - Impaction grafting of the femur in two-stage revision for infected total hip
      replacement.
AB  - We report the mid-term results of femoral impaction grafting which was used in 53
      patients during the second stage of a two-stage revision for an infected total
      hip replacement. We reviewed all cases performed between 1989 and 1998. All
      patients underwent a Girdlestone excision arthroplasty, received local and
      systemic antibiotics and subsequently underwent reconstruction, using femoral
      impaction grafting. Four patients had further infection (7.5%), and four died
      within 24 months of surgery. One patient underwent revision of the stem for a
      fracture below its tip at ten months. This left 44 patients with a mean follow-up
      of 53 months (24 to 122). All had improved clinical scores and a satisfactory
      radiological outcome.

PMID- 12188489
TI  - Stage-IIB osteosarcomas around the knee. A study of MMP-9 in surviving tumour
      cells.
AB  - We studied 55 patients with stage-IIB osteosarcoma around the knee with respect
      to the expression of matrix metalloproteinase (MMP)-9 in the surviving tumour
      cells in surgical resection specimens. They were followed up for a minimum of 2.5
      years. Factors significantly associated with poor overall survival were a high
      serum level of alkaline phosphatase at diagnosis and tumour cells expressing MMP
      9 in the resection specimens. The only factor strongly associated with disease
      free survival was the immunohistochemical status of tumour cells for MMP-9 in the
      resection specimens. The percentage of necrosis after chemotherapy failed
      marginally to reach statistical significance. On Cox regression analysis only MMP
      9 remained significant for overall and disease-free survival.

PMID- 12188490
TI  - Total vertebrectomy for primary malignant tumours of the spine.
AB  - Primary malignant tumours should be resected with wide margins. This may be
      difficult to apply to lesions of the spine. We undertook total vertebrectomy on
      seven patients, four males and three females with a mean age at operation of 26.5
      years (6.3 to 45.8). The mean follow-up was 52.3 months. Histological examination
      revealed a Ewing's sarcoma in two patients and osteosarcoma, leiomyosarcoma,
      spindle-cell sarcoma, chondrosarcoma and malignant schwannoma in one each. In
      five patients, histological examination showed that a wide resection had been
      achieved. At follow-up there was no infection and a permanent neurological
      deficit was only seen in those patients in whom the surgical procedure had
      required resection of nerve roots. Despite the high demands placed on the surgeon
      and anaesthetist and the length of postoperative care we consider total
      vertebrectomy to be an appropriate procedure for the operative treatment of
      primary malignant lesions of the spine.

PMID- 12188491
TI  - The efficacy of the Pavlik harness, the Craig splint and the von Rosen splint in
      the management of neonatal dysplasia of the hip. A comparative study.
AB  - We have reviewed the outcome of 134 hips in 96 children with Graf type-III or
      type-IV dysplasia of the hip on ultrasound examination. We treated 28 affected
      hips in 22 children with the Craig splint, 43 hips in 30 children with the Pavlik
      harness, and 26 hips in 16 children with the von Rosen splint. A total of 37
      affected hips in 28 children was not splinted. All children were less than three
      months of age at referral. Those treated with the von Rosen splint had a
      significantly better ultrasound appearance at 12 to 20 weeks of age and fewer
      radiological abnormalities than those not splinted or treated with the Pavlik
      harness. In the von Rosen group no hip required further treatment with an
      abduction plaster or operation compared with ten in the Pavlik harness group,
      three in the Craig splint group and eight in the group without splintage. Our
      results suggest that the von Rosen splint is more likely to improve the outcome
      of neonatal dysplasia of the hip and a definitive, large-scale randomised trial
      is therefore indicated.

PMID- 12188492
TI  - Hip surveillance in children with cerebral palsy. Impact on the surgical
      management of spastic hip disease.
AB  - We studied prospectively the impact of a hip surveillance clinic on the
      management of spastic hip disease in children with cerebral palsy in a tertiary
      referral centre. Using a combination of primary clinical and secondary
      radiological screening we were able to detect spastic hip disease at an early
      stage in most children and to offer early surgical intervention. The principal
      effect on surgical practice was that more preventive surgery was carried out at a
      younger age and at a more appropriate stage of the disease. The need for
      reconstructive surgery has decreased and that for salvage surgery has been
      eliminated. Displacement of the hip in children with cerebral palsy meets
      specific criteria for a screening programme. We recommend that hip surveillance
      should become part of the routine management of children with cerebral palsy. The
      hips should be examined radiologically at 18 months of age in all children with
      bilateral cerebral palsy and at six- to 12-monthly intervals thereafter. A co
      ordinated approach by orthopaedic surgeons and physiotherapists may be the key to
      successful implementation of this screening programme.

PMID- 12188493
TI  - Staged reduction and stabilisation in chronic atlantoaxial rotatory fixation.
AB  - We present seven children with atlantoaxial rotatory fixation (AARF) of more than
      three months' duration after an injury to the upper cervical spine. The deformity
      was irreducible by skull traction. MRI and MR angiography (MRA) of the vertebral
      arteries were performed in four children. The patients were neurologically
      intact. Thrombosis of the ipsilateral vertebral artery was noted in two patients.
      The deformity was gradually corrected and stabilised after transoral release of
      the atlantoaxial complex, skull traction and posterior atlantoaxial fusion. Soft
      tissue interposition and contractures within the atlantoaxial complex prevented
      closed reduction. MRI and MRA of the vertebral arteries were useful in
      elucidating the pathology of chronic atlantoaxial rotatory fixation.

PMID- 12188494
TI  - Delay in skeletal maturity in Malawian children.
AB  - The atlas of Greulich and Pyle for skeletal maturity and epiphyseal closure is
      widely used in many countries to assess skeletal age and to plan orthopaedic
      surgery. The data used to compile the atlas were collected from institutionalised
      American children in the 1950s. In order to determine whether the atlas was
      relevant to subSaharan Africa, we compared skeletal age, according to the atlas,
      with chronological age in 139 skeletally immature Malawian children and young
      adults with an age range from 1 year 11 months to 28 years 5 months. The height
      and weight of each patient were also measured in order to calculate the body mass
      index. The skeletal age of 119 patients (85.6%) was lower than the chronological
      age. The mean difference was 20.0+/-24.1 months (t-test, p = 0.0049), and the
      greatest difference 100 months. The atlas is thus inaccurate for this group of
      children. The body mass index in 131 patients was below the normal range of 20 to
      25 kg/m2. The reasons for the low skeletal age in this group of children are
      discussed. Poor nutrition and chronic diseases such as malaria and diarrhoea
      which are endemic in Malawi are likely to be contributing factors. We did not
      find any correlation between the reduction in body mass index in our patients and
      the degree of retardation of skeletal age.

PMID- 12188495
TI  - An assessment of the POSSUM system in orthopaedic surgery.
AB  - We describe the development and validation of a scoring system for auditing
      orthopaedic surgery. It is a minor modification of the POSSUM scoring system
      widely used in general surgery. The orthopaedic POSSUM system which we have
      developed gives predictions for mortality and morbidity which correlate well with
      the observed rates in a sample of 2326 orthopaedic operations over a period of 12
      months.

PMID- 12188496
TI  - The cervical rib. A predisposing factor for obstetric brachial plexus lesions.
AB  - Controversy surrounds the aetiology of obstetric brachial plexus lesions. Most
      authors consider that it is caused by traction or compression of the brachial
      plexus during delivery. Some patients, however, present without a history of
      major traction during delivery, and some delivered by Caesarean section also
      suffer the injury. In our series of 42 infants, 28 had an Erb's palsy, and the
      remaining 14 presented with a more extensive lesion, involving the lower roots.
      In five of these, a complete ossified cervical rib was found. We believe that
      anatomical variations, such as cervical ribs or fibrous bands, can cause
      narrowing of the supracostoclavicular space, and render the adjacent nerves more
      susceptible to external trauma.

PMID- 12188497
TI  - Osteonecrosis of the humeral head after extracorporeal shock-wave lithotripsy.
AB  - A 59-year-old woman with calcific tendinitis in her right shoulder underwent
      extracorporeal shock-wave lithotripsy. Three years and four months later she
      presented with osteonecrosis of the head of the right humerus. It is known that
      shock waves in patients with urological disorders can damage blood vessels. A
      possible reason for the development of osteonecrosis in this patient may have
      been damage to the blood supply of the head of the humerus.

PMID- 12188498
TI  - Adjacent vertebral failure after vertebroplasty. A biomechanical investigation.
AB  - Vertebroplasty, which is the percutaneous injection of bone cement into vertebral
      bodies has recently been used to treat painful osteoporotic compression
      fractures. Early clinical results have been encouraging, but very little is known
      about the consequences of augmentation with cement for the adjacent, non
      augmented level. We therefore measured the overall failure, strength and
      structural stiffness of paired osteoporotic two-vertebra functional spine units
      (FSUs). One FSU of each pair was augmented with polymethylmethacrylate bone
      cement in the caudal vertebra, while the other served as an untreated control.
      Compared with the controls, the ultimate failure load for FSUs treated by
      injection of cement was lower. The geometric mean treated/untreated ratio of
      failure load was 0.81, with 95% confidence limits from 0.70 to 0.92, (p < 0.01).
      There was no significant difference in overall FSU stiffness. For treated FSUs,
      there was a trend towards lower failure loads with increased filling with cement
      (r2 = 0.262, p = 0.13). The current practice of maximum filling with cement to
      restore the stiffness and strength of a vertebral body may provoke fractures in
      adjacent, non-augmented vertebrae. Further investigation is required to determine
      an optimal protocol for augmentation.

PMID- 12188499
TI  - The role of inducible nitric oxide synthase in aseptic loosening after total hip
      arthroplasty.
AB  - We collected 16 samples of the membrane which surrounds loose hip prostheses from
      patients undergoing revision operations for aseptic loosening. To serve as the
      control group, samples of the synovial tissue and the fibrous capsular tissue
      were collected from 11 patients undergoing primary hip arthroplasties. Analyses
      of the expression levels of inducible nitric oxide synthase (iNOS), tumour
      necrosis factor-alpha (TNF-alpha), and cytosolic phospholipase A2 (cPLA2) mRNAs
      were performed by a reverse transcription polymerase chain reaction, and the
      content of nitrite was measured by the Griess reaction using sodium nitrite as
      the standard. The expression levels of iNOS, TNF-alpha, and cPLA2 mRNAs in the
      membranes were significantly higher than those in the control samples (p < 0.05).
      The expression levels of iNOS mRNA and the nitrite content in the membranes
      significantly correlated with those of TNF-alpha and cPLA2 mRNAs, respectively.
      In addition, the expression levels of iNOS, TNF-alpha, and cPLA2 mRNAs were
      significantly higher in membranes from cementless than in those from cemented
      implants (p < 0.05). Our results suggest that the expression levels of iNOS, TNF
      alpha, and cPLA2 mRNAs in the membranes are regulated by closely-related
      mechanisms and that these have a significant role in aseptic loosening.

PMID- 12188500
TI  - Development of resistant strains of Staphylococcus epidermidis on gentamicin
      loaded bone cement in vivo.
AB  - We have compared the rates of infection and resistance in an animal model of an
      orthopaedic procedure which was contaminated with a low-dose inoculum of
      Staphylococcus epidermidis. We randomised 44 Sprague-Dawley rats to have bone
      cement implanted subcutaneously containing either gentamicin or saline (control).
      The wound was inoculated with a dilute solution of gentamicin-sensitive
      Staphylococcus epidermidis. At two weeks the cement was retrieved and
      microbiologically tested. A lower overall rate of infection was seen in the
      gentamicin-loaded cement group, but there was a significantly higher rate of
      gentamicin-resistant infection in this group (Fisher's exact test, p < 0.01).
      Antibiotic-impregnated cement has an optimum surface for colonisation and
      prolonged exposure to antibiotic allows mutational resistance to occur.
      Gentamicin-loaded cement may not be appropriate for revision surgery if it has
      been used already in previous surgery.

PMID- 12188501
TI  - Induction of somatosensory evoked potentials by mechanical stimulation in
      reconstructed anterior cruciate ligaments.
AB  - We have determined whether somatosensory evoked potentials (SEPs) were detectable
      after direct mechanical stimulation of normal, injured and reconstructed anterior
      cruciate ligaments (ACLs) during arthroscopy. We investigated the position sense
      of the knee before and after reconstruction, and correlated the SEP with
      instability. Reproducible SEPs were detected in all 19 normal ACLs and in 36 of
      38 ACLs reconstructed during a period of 13 months. Of the 45 injured ACLs,
      reproducible SEPs were detected in 26. The mean difference in anterior
      displacement in the SEP-positive group of the injured ACL group was significantly
      lower than that in the SEP-negative group. In the reconstructed group, the
      postoperative position sense was significantly better than the preoperative
      position sense. Our results indicate not only that sensory reinnervation occurs
      in the reconstructed ACL, but also that the response to mechanical loads can be
      restored, and is strongly related to improvement in position sense.

PMID- 12188502
TI  - Bone-resorptive effects of endotoxin-contaminated high-density polyethylene
      particles spontaneously eliminated in vivo.
AB  - Wear particles commonly used for experiments may carry adherent endotoxin on
      their surfaces, which may be responsible for the observed effects. In this study,
      we attached titanium plates to the tibiae of 20 rats. After osseointegration,
      endotoxin-contaminated or uncontaminated high-density-polyethylene (HDPE)
      particles were applied. Contaminated specimens showed a dramatic resorption of
      bone after seven days but new bone filled the site again at 21 days.
      Uncontaminated specimens showed no resorption. In 18 rats we implanted
      intramuscularly discs of ultra-high-molecular-weight polyethylene (UHMWPE) with
      baseline or excess contamination of endotoxin. Excess endotoxin disappeared
      within 24 hours and the amount of endotoxin remained at baseline level
      (contamination from production). Uncontaminated titanium discs did not adsorb
      endotoxin in vivo. The endotoxin was measured by analytical chemistry. Locally
      applied endotoxin stimulated bone resorption similarly to that in experiments
      with wear particles. Endotoxin on the surface of implants and particles appeared
      to be inactivated in situ. A clean implant surface did not adsorb endotoxin. Our
      results suggest that endotoxin adhering to orthopaedic implants is not a major
      cause for concern.

PMID- 12188504
TI  - Necrotising fasciitis of a limb.

PMID- 12188503
TI  - Conservative versus operative treatment for displaced ankle fractures in patients
      over 55 years of age.

PMID- 12188505
TI  - The translated two-part fracture of the proximal humerus.

PMID- 12188506
TI  - The floating shoulder: a multicentre study.

PMID- 12188507
TI  - Searching for threat.
AB  - In a series of experiments, a visual search task was used to test the idea that
      biologically relevant threatening stimuli might be recognized very quickly or
      capture visuo-spatial attention. In Experiment 1, there was evidence for both
      faster detection and faster search rates for threatening animals than for plants.
      However, examination of the basis of this effect in Experiment 2 showed that it
      was not due to threat per se, as detection and search rate advantages were found
      for pleasant rather than threatening animals compared to plants. In Experiment 3,
      participants searched for the plants and pleasant and threatening animals used in
      Experiments 1 and 2, among a fixed heterogeneous selection of non-target items.
      There was no search rate or detection advantage for threatening animals compared
      to pleasant animals or plants. The same targets and non-targets as those used in
      Experiment 3 were also used in Experiment 4. In Experiment 4, participants
      searched for targets that were presented either close to or distant from an
      initial fixation point. There was no evidence for a "threat" detection advantage
      either close to or distant from the cross. Finally, an experiment was conducted
      in which target categories (fruit, flowers, and animals) were not pre-specified
      prior to each trial block. There were no differences in reaction times to detect
      pleasant animals, threatening animals, or fruit. We conclude that the visual
      search paradigm does not readily reveal any biases that might exist for
      threatening stimuli in the general population.

PMID- 12188508
TI  - Authorship effects in the prediction of handwriting strokes: evidence for action
      simulation during action perception.
AB  - Does the action system contribute to action perception? Recent evidence suggests
      that actions are simulated while being observed. Given that the planning and
      simulating system are the same only when one observes one's own actions, it might
      be easier to predict the future outcomes of actions when one has carried them out
      oneself earlier on. In order to test this hypothesis, three experiments were
      conducted in which participants observed parts of earlier self- and other
      produced trajectories and judged whether another stroke would follow or not. When
      the trajectories were produced without constraints, participants accomplished
      this task only for self-produced trajectories. When the trajectories were
      produced under narrow constraints, the predictions were equally accurate for self
      and for other-generated trajectories. These results support the action
      simulation assumption. The more the actions that one observes resemble the way
      one would carry them out oneself, the more accurate the simulation.

PMID- 12188509
TI  - Cognitive euroscience: scalar variability in price estimation and the cognitive
      consequences of switching to the euro.
AB  - The present paper examines the ability to evaluate prices in a familiar currency
      (French francs, Portugese escudos, or Irish punt) and in an unfamiliar currency
      (euro). Participants evaluated prices for different items either by selecting the
      most appropriate price from a set of alternatives (in a timed or not-timed
      version) or by directly producing a price estimate for each item. The results
      followed Weber's law: The standard deviation of estimated prices was proportional
      to their mean. The Weber fraction was stable for the familiar currency in
      different countries, but was significantly higher for the unfamiliar currency. We
      suggest that price estimation relies on a learned mapping between items and their
      prices as represented by distributions of activation on an internal number line.
      The observed Weber fraction reflects the degree of expertise with a given
      currency as well as a minimal variability intrinsic to the number line itself.

PMID- 12188510
TI  - Representation and retrieval of arithmetical facts: developmental difficulties.
AB  - One form of developmental difficulty with arithmetic affects the storage or
      retrieval of arithmetical facts, such as tables, which are required to implement
      arithmetical computations (Temple, 1991, 1994). Such difficulties may arise
      because of impairment in a specialized system for the storage of arithmetical
      facts or as a result of causally linked impairment in another cognitive domain.
      This study explored issues concerning the representation and retrieval of
      arithmetical facts in children with number fact disorders (NF) and in normal
      children, in particular the status of hypothesized linked impairments: short-term
      memory (STM) spans, counting skills, speed of speech, and speed of number fact
      and lexical retrieval. There was no evidence that NF children had weak STM spans
      on any span measure or that STM spans related to arithmetical fact skills. There
      was also no evidence that NF children had weak counting abilities or free
      counting speeds. The NF children were slower in speeded counting, which also
      correlated with number fact skill. The significance or not of this is discussed.
      The NF children were also slower than controls in speed of speech and on some
      measures of speed of access. However, the absence of correlation with number fact
      skill, the absence of generality across tasks, and the possibility that delayed
      speeds in fact retrieval reflect the use of alternative strategies, together
      suggest that the increased speeds are not causally linked to number fact skill.
      The results are consistent with modular accounts, in which there is a specialized
      system for the storage and retrieval of arithmetical facts.

PMID- 12188511
TI  - Insensitivity of visual short-term memory to irrelevant visual information.
AB  - Several authors have hypothesized that visuo-spatial working memory is
      functionally analogous to verbal working memory. Irrelevant background speech
      impairs verbal short-term memory. We investigated whether irrelevant visual
      information has an analogous effect on visual short-term memory, using a dynamic
      visual noise (DVN) technique known to disrupt visual imagery (Quinn & McConnell,
      1996b). Experiment I replicated the effect of DVN on pegword imagery. Experiments
      2 and 3 showed no effect of DVN on recall of static matrix patterns, despite a
      significant effect of a concurrent spatial tapping task. Experiment 4 showed no
      effect of DVN on encoding or maintenance of arrays of matrix patterns, despite
      testing memory by a recognition procedure to encourage visual rather than spatial
      processing. Serial position curves showed a one-item recency effect typical of
      visual short-term memory. Experiment 5 showed no effect of DVN on short-term
      recognition of Chinese characters, despite effects of visual similarity and a
      concurrent colour memory task that confirmed visual processing of the characters.
      We conclude that irrelevant visual noise does not impair visual short-term
      memory. Visual working memory may not be functionally analogous to verbal working
      memory, and different cognitive processes may underlie visual short-term memory
      and visual imagery.

PMID- 12188512
TI  - Effect of mental imagery on realizing affordances.
AB  - Using a reaction time experiment, we examined whether imagining a response would
      lead to an increase in the frequency of its execution. During a pre-test and a
      post-test, participants had to respond as quickly as possible with either their
      left or their right hand, as they preferred, to the illumination of one of 17
      target positions arrayed in front of them in a semicircle. Between these two
      phases, participants performed a practice condition. Each of 40 right-handed
      participants was assigned to one of four groups that differed in their practice
      condition: One group made only dominant-hand responses to all target locations,
      two imagery groups imagined dominant hand responses to all target locations, and
      the last group received a no-practice, control task. One imagery group received
      instructions emphasizing that imagery has a strong effect; the second group
      received instructions suggesting that imagery was not effective. The results
      showed an increased incidence of the practised response for both imagery groups
      during the post-test. No effect was found for the physical performance group and
      the control group. The change in performance for the imagery groups was not
      accompanied by a change in reaction time. The results are discussed in terms of
      imagining the realization of action possibilities and from a neuropsychological
      point of view.

PMID- 12188513
TI  - Predicting the results of reasoning experiments: reply to Feeney and Handley
      (2000).

PMID- 12188514
TI  - Alternative antecedents, probabilities, and the suppression of fallacies in
      Wason's selection task.
AB  - Three experiments examined the influence of a second rule on the pattern of card
      selections on Wason's selection task. In Experiment 1 participants received a
      version of the task with a single test rule or one of two versions of the task
      with the same original test rule together with a second rule. The probability of
      q was manipulated in the two-rules conditions by varying the size of the
      antecedent set in the second rule. The results showed a significant suppression
      of q card and not-p card selections in the alternative-rule conditions, but no
      difference as a function of antecedent set size. In Experiment 2 the size of the
      antecendent set in the two-rules conditions was manipulated using the context of
      a computer printing double-sided cards. The results showed a significant
      reduction of q card selections in the two-rules conditions, but no effect of p
      set size. In Experiment 3 the scenario accompanying the rule was manipulated, and
      it specified a single alternative antecedent or a number of alternative
      antecedents. The q card selection rates were not affected by the scenario
      manipulation but again were suppressed by the presence of a second rule. Our
      results suggest that people make inferences about the unseen side of the cards
      when engaging with the task and that these inferences are systematically
      influenced by the presence of a second rule, but are not influenced by the
      probabilistic characteristics of this rule. These findings are discussed in the
      context of decision theoretic views of selection task performance (Oaksford &
      Chater, 1994).

PMID- 12188515
TI  - Causal judgement from contingency information: judging interactions between two
      causal candidates.
AB  - In two experiments participants judged the extent to which occurrences and non
      occurrences of an effect could be attributed to an interaction between two causal
      candidates A and B. In Experiment I judgements were influenced by the proportion
      of instances normatively evaluated as confirmatory for the interaction
      interpretation, when the objective contingency was held constant. Information
      about instances in which both candidates were present and the effect occurred was
      more influential than information about instances in which both candidates were
      absent and the effect did not occur. In Experiment 2 the occurrence rate of the
      effect when both candidates were present, when A alone was present, when B alone
      was present, and when both were absent was manipulated. Interaction judgements
      were mainly determined by occurrence rate when both were present. There was also
      a significant effect of occurrence rate when both were absent, but the other two
      occurrence rates had no significant effect. These results are interpreted as
      supporting a general model in which causal judgements are made according to the
      proportion of instances evaluated as supporting the interpretation being judged.

PMID- 12188516
TI  - Content and context effects in children's and adults' conditional reasoning.
AB  - We have recently shown that children interpret conditional sentences with binary
      terms (e.g., male/female) in both the antecedent and the consequent as
      biconditionals (Barrouillet & Lecas, 1998). We hypothesized that the same effect
      can be obtained with conditionals that do not contain binary terms provided that
      they are embedded in a context that restricts to only two the possible values on
      both the antecedent and the consequent. In the present experiment, we asked 12
      year-old children, 15-year-old children, and adults to draw conclusions from
      conditional syllogisms that involved three types of conditional sentence: (1)
      conditionals with binary terms (BB), (2) conditionals with non-binary terms (NN),
      and (3) conditionals with non-binary terms embedded in a restrictive context
      (NNR). As we predicted, BB conditionals elicited more biconditional response
      patterns than did NN conditionals in all age groups. On the other hand,
      manipulating the context had the same effect in children but not in adults.
      Content and context constraints on conditional reasoning along with developmental
      issues are discussed within the framework of the mental models theory.

PMID- 12188517
TI  - Paap and Noel revisited: individual differences in independent word recognition
      tasks in relation to the dual-task paradigm.
AB  - Paap and Noel (1991) found that participants' pronunciation latencies were faster
      for low-frequency irregular words when named under a concurrent high digit memory
      load than when named under a low load. The effects reported by Paap and Noel
      haveproved difficult to replicate in subsequent studies. The present research
      suggests that individual differences in word recognition skill relate to who will
      or will not show these effects. In two experiments, participants were allocated
      to skill groups on the basis of latency in tasks tapping lexical and sub-lexical
      reading processes. In both studies, only one group (the "intermediate skilled"),
      showed evidence of such effects. A combined analysis of the data from Experiments
      1 and 2 was carried out. This confirmed and extended the analyses of the
      individual experiments. The results are discussed in relation to contemporary
      models of word recognition.

PMID- 12188518
TI  - The correspondence between sentence production and corpus frequencies in modifier
      attachment.
AB  - We examined the production of relative clauses in sentences with a complex noun
      phrase containing two possible attachment sites for the relative clause (e.g.,
      "Someone shot the servant of the actress who was on the balcony."). On the basis
      of two corpus analyses and two sentence continuation tasks, we conclude that much
      research about this specific syntactic ambiguity has used complex noun phrases
      that are quite uncommon. These noun phrases involve the relationship between two
      humans and, at least in Dutch, induce a different attachment preference from noun
      phrases referring to non-human entities. We provide evidence that the use of this
      type of complex noun phrase may have distorted the conclusions about the
      processes underlying relative clause attachment. In addition, it is shown that,
      notwithstanding some notable differences between sentence production in the
      continuation task and in coherent text writing, there seems to be a remarkable
      correspondence between the attachment patterns obtained with both modes of
      production.

PMID- 12188519
TI  - How predictable is spelling? Developing and testing metrics of phoneme-grapheme
      contingency.
AB  - Prior research has purported to show that words with infrequent phoneme-grapheme
      correspondences are more difficult to spell than words with frequent phoneme
      grapheme correspondences. Defining exactly what a phoneme-grapheme relationship
      is, however, is not necessarily straightforward. There are a number of different
      assumptions that can be made. In this study, we developed four metrics of sound
      spelling contingency based on all monosyllabic English words, including those
      with complex morphology. These metrics differed in the extent to which they
      included assumptions about spelling. The psychological reality of these different
      metrics was evaluated against data from a large-scale study of skilled adult
      spelling and a nonword spelling experiment. The results suggest that when
      spelling, people are sensitive to positional information, morphological status,
      vowel type, and a number of more idiosyncratic constraints.

PMID- 12188521
TI  - Head-centred meridian effect on auditory spatial attention orienting.
AB  - Six experiments examined the issue of whether one single system or separate
      systems underlie visual and auditory orienting of spatial attention. When
      auditory targets were used, reaction times were slower on trials in which cued
      and target locations were at opposite sides of the vertical head-centred meridian
      than on trials in which cued and target locations were at opposite sides of the
      vertical visual meridian or were not separated by any meridian. The head-centred
      meridian effect for auditory stimuli was apparent when targets were cued by
      either visual (Experiments 2, 3, and 6) or auditory cues (Experiment 5). Also,
      the head-centred meridian effect was found when targets were delivered either
      through headphones (Experiments 2, 3, and 5) or external loud-speakers
      (Experiment 6). Conversely, participants showed a visual meridian effect when
      they were required to respond to visual targets (Experiment 4). These results
      strongly suggest that auditory and visual spatial attention systems are indeed
      separate, as far as endogenous orienting is concerned.

PMID- 12188520
TI  - Covert orienting to the locations of targets and distractors: effects on response
      channel activation in a flanker task.
AB  - The role of covert orienting of attention in response channel activation was
      examined using the flanker interference and precueing paradigms. Four experiments
      assessed the influence of distractors on the discrimination of a target colour
      patch undercueing conditions (three with noninformative, exogenous cues and one
      with informative, endogenous cues) that modulated attention at the flanker or
      target locations. Across all of the experiments, the amount of interference
      generated by the distractors was not modulated by the facilitation and inhibition
      of return induced by spatial attention precues. These results are consistent with
      previous reports of patients with neglect, which demonstrated that flanker
      interference proceeds at unattended locations (Audet, Bub, & Lecours, 1991;
      Cohen, Ivry, Rafal, & Kohn, 1995), and they suggest that response channel
      activation can occur independently from spatial attention.

PMID- 12188522
TI  - Outcome and cue properties modulate blocking.
AB  - Participants saw a series of situations in which a cue (a light appearing at a
      certain position) could be followed by an outcome (a drawing of a tank that
      exploded) and were afterwards asked to rate the likelihood of the outcome in the
      presence of the cue. In Experiments 1 and 2, the compound cues AT and KL were
      always followed by the outcome (AT+, KL+). During an elemental phase that either
      preceded or followed the compound phase, Cue A was also paired with the outcome
      (A+). Cue T elicited a lower rating than Cues K and L when cues were described as
      being weapons but not when the cues were said to be indicators. The magnitude of
      this blocking effect was also influenced by whether the outcome occurred to a
      maximal or submaximal extent. Experiment 3 replicated the effect of cue
      instructions on blocking (A+, AT+) but showed that cue instructions had no impact
      on reduced overshadowing (B-, BT+). The results shed new light on previous
      findings and support probabilistic contrast models of human contingency
      judgements.

PMID- 12188523
TI  - The effects of endogenous attention and stimulus onsets on encoding target
      location.
AB  - The effects of endogenously attended and non-attended stimulus onsets on spatial
      stimulus encoding of a target wereexplored in a Simon task. In each experiment
      participants madespeeded left or right key-press responses to the colour of a
      target that followed a cueing display consisting of several shapes. The target
      appeared within some shapes and not others. The target's spatial code as measured
      by a Simon task was its location relative to possible target positions and
      relative to the centre of the display. Target location was not coded relative to
      the positions of onset shapes that could not contain a target. These spatial
      coding effects were found at cue-target intervals of 50, 300, and 1000 ms. The
      data indicate that target location is defined relative to the distribution of
      endogenous attention and reference frames aligned with the centre of the display
      and that the spatial code assigned to a target is not affected when attention is
      shifted in the target's direction.

PMID- 12188525
TI  - Extinction of conditioned taste aversions: effects of concentration and
      overshadowing.
AB  - Extinction of conditioned taste aversions was examined as a function of taste
      concentration and of the presence of an additional taste. The results of
      Experiment 1 were consistent with previous evidence in that a conditioned
      aversion to high concentration saline was more persistent in extinction than an
      aversion to a low concentration. However, when floor effects were avoided the
      rate of extinction was faster for the higher (1%) concentration than for 0.2%
      saline (Experiment 2), a result consistent with accounts of extinction in other
      preparations. Three further experiments examined extinction of a conditioned
      sucrose aversion. The addition of 1% saline, but not of 0.2% saline, to sucrose
      during extinction produced overshadowing ("protection from extinction";
      Experiment 3). Such overshadowing by saline was detected after two, but not after
      a single extinction trial (Experiment 4). This last finding suggests that under
      the conditions of the present experiments sweet and salty tastes function as
      elemental stimuli competing for loss of associative strength. No overshadowing
      was found when almond (an aqueous odour) was used in place of saline as the added
      stimulus, even when high concentrations of almond were used that produced
      observable neophobia (Experiments 5A and 5B).

PMID- 12188524
TI  - Speeding up an internal clock in children? Effects of visual flicker on
      subjective duration.
AB  - Children of 3, 5, and 8 years of age were trained on a temporal bisection task
      where visual stimuli in the form of blue circles of 200 and 800 ms or 400 and
      1600 ms duration, preceded by a 5-s white circle, served as the short and long
      standards. Following discrimination training between the standards, stimuli in
      the ranges 20-800 ms or 400-1,600 ms were presented with the white circle either
      constant or flickering. Relative to the constant white circle, the flicker (1)
      increased the proportion of "long" responses (responses appropriate to the long
      standard), (2) shifted the psychophysical functions to the left, (3) decreased
      bisection point values, at all ages, and (4) did not systematically affect
      measures of temporal sensitivity, such as difference limen and Weber ratio. The
      results were consistent with the idea that the repetitive flicker had increased
      the speed of the pacemaker of an internal clock in children as young as 3 years.
      The "pacemaker speed" interpretation of the results was further strengthened by a
      greater effect of flicker in the 400/ 1,600-ms condition than in the 200/800-ms
      condition.

PMID- 12188526
TI  - Human agency and associative learning: Pavlovian principles govern social process
      in causal relationship detection.
AB  - Estimates of a worker's causal relationship (CR) to production obeyed associative
      principles, despite the participants' a priori beliefs that workers are
      responsible or "at cause" for production. In three experiments, social analogues
      of conditioned stimuli (workers) and unconditioned stimuli (company production
      information) were manipulated in familiar Pavlovian paradigms. The findings
      included (1) CR acquisition, (2) unconditioned stimulus-intensity effects, and
      (3) CR blocking. The research plan employed an approach that Neal Miller (1959)
      termed "extension of liberalized S-R theory" and drew on the Rescorla-Wagner
      model to integrate the experimental results, to illuminate the empirical data of
      social attribution research, and to guide the study of causal relationship
      detection using social stimuli.

PMID- 12188527
TI  - Judgement frequency, belief revision, and serial processing of causal
      information.
AB  - The main aim of this research was to study the cognitive architecture underlying
      causal/covariation learning by investigating the frequency of judgement effect.
      Previous research has shown that decreasing the number of trials between
      opportunities to make a judgement in a covariation learning task led to a higher
      score after an a or d type of trial (positive cases) than after b and c trials
      (negative cases). Experiment I replicated this effect using a trial-by-trial
      procedure and examined the conditions under which it occurs. Experiment 2
      demonstrated a similar frequency of judgement effect when the information was
      presented in the form of contingency tables. Associative or statistical single
      mechanism accounts of causal and covariation learning do not provide a
      satisfactory explanation for these findings. An alternative belief revision model
      is presented.

PMID- 12188528
TI  - Anaerobic digestion: concepts, limits and perspectives.
AB  - Anaerobic degradation processes are faced with limitations with respect to
      reaction energetics and reaction kinetics. The small amount of energy available
      in methanogenic degradation of complex organic compounds allows in most cases
      only the conservation of minimum amounts of energy in the lowest range of energy
      exploitable by biochemical reactions for ATP-synthesis. This limit has to be
      defined in the range of 1/3-1/4 of an ATP unit, or 15-20 kJ per mol reaction.
      Such small amounts of energy are exploited efficiently by syntrophic microbial
      communities co-operating e.g. in fatty acid conversion to methane and CO2.
      Methanogens also set the stage for efficient conversion of sugars or amino acids,
      and channel electron fluxes to the utmost efficiency. Kinetic limitations are set
      by the inertness of certain compounds, e.g. hydrocarbons, to react in the absence
      of a strong oxidant. New reactions have been found recently which activate such
      compounds, e.g. aromatic hydrocarbons such as toluene, xylenes, naphthalene,
      methane, or ammonia. Refined techniques for analysis of microbial activities in
      ill defined natural environments such as digestive tracts of small invertebrates
      or polluted aquifers have shown an amazing capacity for anaerobic or oxygen
      limited degradation processes that are still to be exploited. Thus, anaerobic
      digestion is still a matter of fast increasing knowledge, both on the side of
      basic research as well as on the side of application in treatment of soil, waste
      materials, or in understanding complex living communities.

PMID- 12188529
TI  - Kinetics and inhibition during the decolorization of reactive anthraquinone dyes
      under methanogenic conditions.
AB  - The objective of this study was to assess the biological decolorization of two
      reactive anthraquinone dyes (Reactive Blue 4, RB 4; Reactive Blue 19, RB 19)
      under methanogenic conditions. Using a mixed, methanogenic culture, batch assays
      were performed to evaluate both the rate and extent of color removal as well as
      any potential inhibition. The effect of initial dye, biomass, and organic feed
      concentration, as well as the effect of repetitive dye addition on color removal
      kinetics and culture inhibition were assessed. Overall, a lower rate and extent
      of color removal was observed in RB 4-amended cultures as opposed to the RB 19
      amended cultures. For an incubation time of ca. 15 days and an initial dye
      concentration of 2000 mg/L, the extent of color removal was 50 and 95% for RB 4
      and RB 19, respectively. Inhibition of acidogenesis and to a larger degree of
      methanogenesis, resulting in accumulation of volatile fatty acids, was observed
      in both RB 4- and RB 19-amended cultures. Although the degree of inhibition
      varied among the two dyes tested (RB 19 was more inhibitory than RB 4), an
      increase of inhibition was observed with increasing initial dye concentration. At
      an initial dye concentration of 500 mg/L or higher, methane production was lower
      than 6% of that of the control culture for both RB 4 and RB 19. However, color
      removal occurred despite culture inhibition.

PMID- 12188530
TI  - Ammonia inhibition on thermophilic aceticlastic methanogens.
AB  - The inhibition effects of total ammonia nitrogen (TAN) on aceticlastic
      methanogenic activity using biomass from thermophilic anaerobic reactors were
      investigated in this study. Anaerobic Toxicity Assays (ATA) were conducted after
      the biomass was acclimated to different levels of TAN. The TAN background
      concentrations in the reactors were 400, 1,200, and 3,050 mg/L. The results from
      ATA showed: 1) high TAN concentrations could cause inhibition of aceticlastic
      methanogens; 2) biomass acclimated to higher TAN concentrations could alleviate
      the inhibition effect due to the increase of TAN concentration; 3) the lethal TAN
      concentration for methanogens was approximately 10,000 mg/L regardless of the
      background TAN concentration; 4) ATA results also revealed the role played by pH.
      At a given TAN concentration, methanogenic activity varied with the pH values.
      The highest methanogenic activity was always observed at a pH of 7.0-7.5. 5) It
      was also observed that acclimation could increase the pH tolerance range, which
      made methanogens less sensitive to pH changes.

PMID- 12188531
TI  - Effect of high salinity on the fate of methanol during the start-up of
      thermophilic (55 degrees C) sulfate reducing reactors.
AB  - Two 6.5 L lab-scale upflow anaerobic sludge bed (UASB) reactors were operated at
      55 degrees C fed with methanol as the sole electron and carbon source and in
      excess of sulfate (COD/SO4(2-) of 0.5) in order to investigate the effect of high
      wastewater salinity on the start-up period. The first reactor (UASB I) was
      operated without NaCl addition, while the second reactor (UASB II) was fed with
      25 g x L(-1) of NaCl in the first 13 days of operation. Successful start-up of
      UASB I was achieved, with full methanol conversion (100% elimination) to methane
      gas (methane production rate up to 3.66 gCOD.L(-1).day(-1)). Despite the
      detection of sulfide from day 15 onwards in UASB I, methane was the main
      mineralization product when operating at an organic loading rate (OLR) of 5
      gCOD.L(-1).day(-1) and a hydraulic retention time (HRT) of 10 hours. Sulfide and
      acetate started to be produced after salt omission from the influent in UASB II
      at day 13, with no detection of methane. Acetate was the main product when
      operating at an OLR of 10 gCOD.L(-1).day(-1) and HRT of 6.5 hours in both
      reactors. Apparently, the methane producing bacteria (MPB) are the trophic group
      most sensible to the NaCl shock.

PMID- 12188532
TI  - Characterization of soluble microbial products (SMP) in effluents from anaerobic
      reactors.
AB  - The residual COD from anaerobic treatment processes is usually too high to comply
      with legislative discharge levels. It has been shown that in well operated
      systems the majority of the effluent COD originates from soluble microbial
      products (SMP) produced by the system itself, hence the characteristics of these
      compounds become important when assessing post-treatment systems to remove the
      residual COD. The molecular weight (MW) distribution and the identification of
      SMP in the effluents from three different anaerobic reactors will be presented.
      It has been found that the bulk of SMP lies in the low MW range, though compounds
      with MW as high as 300 kDa were also present in all anaerobic effluents.
      Preliminary results on the identification of such compounds using GC/MS
      surprisingly revealed the presence of long chain alkenes (C12-C24) and alkanes
      (C12-C16), as well as some aromatic compounds. These compounds that likely come
      from cell lysis and endogenous decay may not be easily biodegradable, hence their
      presence in the effluent is likely to cause the residual COD.

PMID- 12188533
TI  - On-line measurements of COD, TOC, VFA, total and partial alkalinity in anaerobic
      digestion processes using infra-red ectrometry.
AB  - This paper describes the use of a Fourier Transform Infra-Red (FT-IR)
      spectrometer as an on-line sensor to measure Chemical Oxygen Demand (COD), Total
      Organic Carbon (TOC), Volatile Fatty Acids (VFA), and Partial and Total
      Alkalinity (PA and TA) in anaerobic digestion processes for the treatment of
      industrial wastewaters. Comparison with manual off-line analysis and with an on
      line industrial TOC analyser and an on-line titrimetric sensor (for the
      measurements of VFA, TA and PA) are provided to demonstrate the interest of
      spectral analysis in the mid infra-red domain for the monitoring of anaerobic
      digestion processes. In order to further illustrate the advantages of using such
      a technique, on-line measurements recorded during an accident of the pH
      regulation in the input (pH in the reactor went above 11 and biomass activity
      stopped) are shown. They demonstrate that, if carefully performed, the
      calibration can be extended outside its range while being still compatible with
      requirements of wastewater treatment processes.

PMID- 12188534
TI  - Anaerobic degradation of oleic acid by suspended and granular sludge:
      identification of palmitic acid as a key intermediate.
AB  - The aim of the present work was to study the maximum potential methane production
      in batch assays of sludge samples taken along the operation of two EGSB reactors
      (RI inoculated with granular sludge and RII inoculated with suspended sludge) fed
      with increasing oleic acid concentrations between 2 and 8 gCOD/l (HRT = 1 day).
      After removing the residual substrate, the sludge was incubated in batch vials
      without any added carbon source. A maximum methane production rate of 152+/-21
      mlCH4(STP)/gVS.day was obtained for the suspended sludge taken on day 70, when
      oleate at a concentration of 2 g COD/l was fed with a co-substrate (50% COD). The
      maximum plateau achieved in the methane production curve was 1145+/-307
      mlCH4(STP)/gVS, obtained for the suspended sludge taken on day 162, when oleate
      was fed as the sole carbon source at 6 g COD/I. The methanization rate of the
      adsorbed substrate was enhanced under stirring conditions and was inhibited by
      adding oleic acid. Extraction and GC analysis confirmed that the main adsorbed
      substrate was palmitate, and not oleate. Accumulated palmitate adsorbed onto the
      sludge and further beta-oxidation was inhibited when in the presence of oleic
      acid. If oleic acid was removed from the medium beta-oxidation proceeded with
      methane production. Suspended sludge was more efficient than granular sludge.

PMID- 12188535
TI  - Start-up of a thermophilic methanol-fed UASB reactor: change in sludge
      characteristics.
AB  - Experiments were performed to study the change in sludge characteristics and
      sludge granulation during the start-up of a thermophilic methanol-fed upflow
      anaerobic sludge bed (UASB) reactor. The laboratory scale reactor, was inoculated
      with thermophilic granular sludge and operated at 55 degrees C over 130 days at
      organic loading rates (OLR) varying from 2.7 to 47 gCOD.L(-1).d(-1). Physical
      characterisation was performed for both the seed and the cultivated sludge.
      Results demonstrated that a good quality, well settleable granular sludge was
      cultivated and retained in the reactor, allowing an OLR of 47 gCOD.L.d(-1) with
      93% of methanol removal, where 79% was converted into methane. Using a community
      analysis of the cultivated consortia, high numbers of rod-shaped hydrogenotrophic
      methanogens were enumerated. Biomass washout coincided with a high specific gas
      load, but was not detrimental to the system in the conditions tested.

PMID- 12188536
TI  - Removal of 3-chlorobenzoate using an upflow anaerobic sludge blanket reactor
      under light conditions.
AB  - The possibility of 3-chlorobenzoate removal from water using an upflow anaerobic
      sludge blanket (UASB) reactor without the addition of any extra dechlorinating
      culture under light conditions has been studied on a laboratory scale. Benzoate
      removal was observed in the first three months of operation under light
      conditions, but the 3-chlorobenzoate removal was not observed. After three months
      of operation under light conditions, the 3-chlorobenzoate concentration in the
      UASB reactor effluent gradually decreased to less than 1 mg x h(-1). The 3
      chlorobenzoate concentration in the effluent did not increase under dark
      conditions. The DOC concentration in the effluent decreased according to the
      removal of the 3-chlorobenzoate by the UASB granules. These results indicated
      that granules in the UASB reactor provided the 3-chlorobenzoate removability
      after 80-100 d of adaptation to the 3-chlorobenzoate, and that the UASB reactor
      is useful for 3-chlorobenzoate removal.

PMID- 12188537
TI  - Physical modelling of an upflow anaerobic sludge blanket reactor: near-field
      study.
AB  - This paper presents a physical evaluation of an upflow anaerobic sludge blanket
      reactor. Specifically, the study contemplates the region influenced by the
      wastewater inlet jets at the bottom of the reactor, here termed the near-field
      area. A three-dimensional physical model of a UASB reactor in reduced scale,
      geometrically and dynamically correlated to a full-scale prototype was used in
      the evaluation. From the analysis of the major forces acting and of the physical
      properties investigated in the prototype, it was possible to establish non
      dimensional relations that were applied to the reduced scale model, allowing the
      investigation of the phenomenon of interest. Tests were developed on the model to
      visualise the inlet flows under the buoyant effect at the bottom of the reactor,
      through the injection of a tracer fluid in the area with higher density,
      simulating the effects of the sludge bed. Based on the experimental results, it
      was possible to provide dimensioning criteria for the jet distribution system in
      UASB reactors.

PMID- 12188538
TI  - Influence of pulsation on start-up of UASB reactors.
AB  - The aim of this work is to study the influence of pulsation on the start-up of
      lab-scale UASB reactors. Pulsation was produced by an Elastic Membrane Pulsator
      (EMP). The application of this device in previous works improved the performance
      of continuous fixed-bed fermentors and reduced the formation of preferential
      pathways, the retention of gas metabolites within the bed and the resistance to
      mass transfer. These characteristics seem to be suitable for feeding UASB
      reactors. In this work, the influence of pulsation frequency was studied in two
      pulsed UASB reactors operated in parallel with a non-pulsed one. One of them (P1)
      operated at high frequencies (periods of 50 and 200 s between each pulsation) and
      the other (P2) at low frequencies (periods of 3600 and 900 s between each
      pulsation). An important improvement of the removal efficiency for pulsed
      reactors with respect to the non-pulsed one was obtained. The structure of the
      biomass was observed at the end of the process by scanning electron microscopy.
      In general, granulation of biomass was improved when operating in pulsing form.

PMID- 12188539
TI  - Retention of granular sludge at high hydraulic loading rates in an anaerobic
      membrane bioreactor with immersed filtration.
AB  - This study shows the results of an Anaerobic Membrane Bioreactor with immersed
      filtration cartridges for granular biomass retention working at high hydraulic
      loading rates. Biomass retention capabilities, granular biomass structure and
      activity, filtration cartridges flux and organic material degradation performance
      were evaluated. Four reactors with a volume of 0.005 m3 were tested. Two
      different filtration cartridges were used (10 and 100 microm) with effective
      surface area of 0.05 m2. The filtration cartridges were submerged in the reactors
      for suction type filtration. Three organic loading rates were tested in the first
      two reactors and seven in the other two. Selective biomass washout and an
      increment in the biomass methanogenic activity was observed in the reactors at
      hydraulic loading rates between 1.2 and 4.5 m/h. Analyses of biomass granulometry
      showed an increase of larger size granular biomass. The immersed membrane
      anaerobic bioreactor maintain most of the advantages without biomass activity
      loss.

PMID- 12188540
TI  - Anaerobic degradation of BTEX in a packed-bed reactor.
AB  - A bench-scale horizontal-flow anaerobic immobilized biomass (HAIB) reactor was
      assayed aiming to verify its performance in degrading benzene, toluene,
      ethylbenzene and xylene (BTEX). A 138 ml HAIB reactor filled with polyurethane
      foam matrices containing immobilized anaerobic biomass was initially fed with
      synthetic substrate containing protein, carbohydrates and lipids. Thereafter,
      BTEX degradation was evaluated in the presence of the co-solvents ethanol and
      lineal alkylbenzene sulphonate (LAS), in two sequential experiments. The inlet
      BTEX concentration ranged from 1.3 to 27.0 mg/L of each compound and outlet
      concentrations were lower than 0.1 mg BTEX/L for both the experiments with
      ethanol and LAS. An active enriched microbial consortium was observed in the
      reactor, containing BTEX-degraders, and also acetogenic, acetotrophic and
      hydrogenotrophic microorganisms. The results from the most probable number (MPN)
      tests indicated a decrease in the number of methanogenic archae, while the number
      of anaerobic microorganisms in the biofilm was maintained during the experimental
      period. Methanogenic archae were found to represent less than 0.5 % of the total
      anaerobic organisms in the biomass inside the reactor.

PMID- 12188541
TI  - Anaerobic treatment of domestic sewage: established technologies and
      perspectives.
AB  - The use of anaerobic reactors for domestic sewage treatment has increased
      significantly since the UASB configuration started to be efficiently applied for
      this purpose in the beginning of the 1980s. Nowadays, hundreds of UASB reactors,
      or similar anaerobic units, are used in domestic sewage treatment systems,
      particularly in developing countries. These units have been operated at ambient
      temperature, normally higher than 20 degrees C, at hydraulic detention time in
      the range of 6 to 10 hours, and organic loading rates lower than 3.0 kg COD.m(
      3).d(-1). They have presented COD removal efficiencies in the range of 65% to
      80%. Besides, new configurations have been developed and assayed in research
      centres, aiming to amplify the range of application and to improve process
      performance. At the same time, research is being conducted on the post-treatment
      of anaerobic effluents attempting to offer alternatives to the existing
      conventional systems. It takes into consideration not only sanitation and
      environmental protection, but also considers resources conservation at lower
      construction and running costs as the main supporting concepts for further
      development. This text presents some aspects of the consolidated technologies and
      suggests on further developments in the conception of domestic sewage treatment
      systems having the anaerobic process as their core.

PMID- 12188542
TI  - The influence of calcium on granular sludge in a full-scale UASB treating paper
      mill wastewater.
AB  - Calcium precipitation can have a number of effects on the performance of high
      rate anaerobic performance including cementing of the sludge bed, limiting
      diffusion, and diluting the active biomass. The aim of this study was to observe
      the influence of precipitation in a stable full-scale system fed with high
      calcium paper factory wastewater. Granules were examined from an upflow anaerobic
      sludge blanket reactor (volume 1,805 m3) at a recycled paper mill with a loading
      rate of 5.7-6.6 kgCOD.m(-3).d(-1) and influent calcium concentration of 400-700
      gCa m(-3). The granules were relatively small (1 mm), with a 200-400 microm core
      of calcium precipitate as observed with energy dispersive X-ray spectroscopy.
      Compared to other granules, Methanomicrobiales not Methanobacteriales were the
      dominant hydrogen or formate utilisers, and putative acidogens were filamentous.
      The strength of the paper mill fed granules was very high when compared to
      granules from other full-scale reactors, and a partial linear correlation between
      granule strength and calcium concentration was identified.

PMID- 12188544
TI  - Expert system for the on-line diagnosis of anaerobic wastewater treatment plants.
AB  - A diagnosis system for anaerobic wastewater treatment processes is presented. The
      system is able to recognise the state and trend of the operation and suggest the
      appropriate control action. The on-line variables measured were gas flow rate and
      composition (methane and carbon monoxide), feed and recycling flow rates,
      temperature and pH, while the manipulable inputs are feed, recycling and buffer
      addition flow rates. The diagnosis system comprises a structured rule base,
      incorporating expert knowledge using fuzzy logic features. The structure of the
      system is based on the classification of information related to the process in
      three categories: i) the state of the process, ii) its trend and iii) the
      recommended set-point values for the inputs manipulated: feeding, buffer and
      recycling pumps. The system was applied to diagnose the operation of a 1.1 m3
      hybrid UASB-UAF treating wastewater from a fibreboard production factory under
      different conditions (overload and underload), corresponding to some of the
      typical causes of destabilisation in anaerobic wastewater treatment plants. These
      situations require control action in order to maintain the stability and the
      treatment capacity of the reactor. The application of the system developed for
      the purpose of managing the situation proved to be reliable for supplying the
      actual state and trend of the process, as well as the adequate set point values
      to recover stable operation and/or to avoid further destabilisation.

PMID- 12188543
TI  - Molecular and conventional analyses of microbial diversity in mesophilic and
      thermophilic upflow anaerobic sludge blanket granular sludges.
AB  - The microbial community structure of mesophilic (35 degrees C) and thermophilic
      (55 degrees C) methanogenic granular sludges was surveyed by using both
      cultivation-independent molecular approach and conventional cultivation technique
      in order to address the fundamental questions on the microbial populations, i.e.
      who are present, where they are located, and what they are doing there. To
      elucidate the microbial constituents within both sludges, we first constructed
      16S ribosomal DNA clone libraries, and partial sequencing of the clones was
      conducted for phylogenetic analysis. In this experiment, we found a number of
      unidentifiable clones within the domain Bacteria as well as clones that were
      closely related with 16S rDNAs of cultured microbes. The unidentifiable clones
      accounted for approximately 60-70% of the total clones in both mesophilic and
      thermophilic libraries. 16S rRNA-targeted in situ hybridization combined with
      confocal laser scanning microscopy was subsequently employed to examine where the
      uncultured populations were located within sludge granules. Spatial organization
      of uncultured microbes was visualized in thin-sections of both types of granules
      using fluorescent oligonucleotide probes, which were designed based on the clone
      sequences of certain novel clusters. This resulted in the detection of two types
      of uncultured cells in specific locations inside the granules. Finally, the goal
      directed conventional cultivation technique was employed to recover such
      uncultured anaerobes and uncover their physiology and functions. In this
      approach, a total of five new species of thermophilic microorganisms were
      isolated, including several types of syntrophs and a novel sugar-fermenting
      bacterium. In the previous molecular approaches, all of these isolates were
      suggested to be significant populations within thermophilic granular sludge,
      hence obtaining these isolates in pure culture decreased the fraction of unknown
      clones in the previous thermophilic clone library from 70% to 40%. In conclusion,
      these approaches successfully revealed biodiversity and spatial organization of
      microbes of interest in sludge granules, and enlarged the fundamental knowledge
      of microbial constituents functioning as significant populations in the UASB
      processes.

PMID- 12188545
TI  - Acidogenesis of dairy wastewater at various pH levels.
AB  - Continuous experiments were conducted to study the influence of pH in the range
      4.0-6.5 on the acidification of dairy wastewater at 37 degrees C with 12 hours of
      hydraulic retention in an upflow reactor. Results showed that degradation of
      dairy pollutants increased with pH from pH 4.0 to 5.5. At pH 5.5, 95% of
      carbohydrate, 82% of protein and 41% of lipid were degraded. Based on chemical
      oxygen demand (COD), 48.4% of dairy pollutants were converted into volatile fatty
      acids and alcohols in the mixed liquor, 6.1% into hydrogen and methane in biogas,
      and the remaining 4.9% into biomass. The biomass yield at pH 5.5 was estimated as
      0.32 mg-VSS/mg-COD. Further increase of pH, up to 6.5, increased degradation of
      carbohydrate, protein and lipid only slightly, but resulted in the lowering of
      overall acid and alcohol production due to their increased conversion into
      methane. Acetate, propionate, butyrate and ethanol are the main products of
      acidogenesis. Productions of propionate and ethanol were favored at pH 4.0-4.5,
      whereas productions of acetate and butyrate were favored at pH 6.0-6.5.

PMID- 12188546
TI  - Treatment of fish processing wastewater in a one- or two-step upflow anaerobic
      sludge blanket (UASB) reactor.
AB  - The performance of one-step UASB reactors treating fish processing wastewater of
      different lipid levels was determined using artificially generated influent
      simulating that of the canning of sardines and tuna. The organic loading rates
      (OLR) and the hydraulic retention times (HRT) were 5-8 g COD.l(-1).d(-1) and 11
      12 hours, respectively. In treating a wastewater that contains 3-4 g.l(-1) total
      COD of which 5-9% was lipids, the COD removal and conversion to methane were
      ca.78% and 61%, respectively. In treating a wastewater with a higher lipid
      content (ca. 47% of the total COD), the total COD removed and converted to
      methane were 92% and 47%, respectively. A considerable part of the influent total
      COD was removed via adsorption on reactor surfaces and sludge particles. The
      adsorption of lipids on sludge particles threatens the stability of the UASB
      operation. Thus, the performance of a first-step UASB reactor in removing
      suspended solids (SS) from a "high-lipid" wastewater was also determined in this
      study.

PMID- 12188547
TI  - Anaerobic digestion of olive oil mill effluents together with swine manure in
      UASB reactors.
AB  - Combined anaerobic digestion of olive oil mill effluent (OME) with swine manure,
      was investigated. In batch experiments was shown that for anaerobic degradation
      of OME alone nitrogen addition was needed. A COD:N ratio in the range of 65:1 to
      126:1 was necessary for the optimal degradation process. Furthermore, it was
      found that methane productions rates during digestion of either swine manure
      alone or OME alone were much lower than the rates achieved when OME and manure
      were digested together. Admixing OME with manure at a concentration of 5 to 10%
      OME resulted in the highest methane production rates. Using upflow anaerobic
      sludge blanket (UASB) reactors, it was shown that codigestion of OME with swine
      manure (up to 50% OME) was successful with a COD reduction up to 75%. The process
      was adapted for degradation of OME with stepwise increase of the OME load to the
      UASB reactor. The results showed that the high content of ammonia in swine
      manure, together with content of other nutrients, make it possible to degrade OME
      without addition of external alkalinity and without addition of external nitrogen
      source. Anaerobic treatment of OME in UASB reactors resulted in reduction of
      simple phenolic compounds such as mequinol, phenyl ethyl alcohol and ethyl methyl
      phenol. After anaerobic treatment the concentration of these compounds was
      reduced between 75 and 100%. However, the concentration of some degradation
      products such as methyl phenol and ethyl phenol were detected in significantly
      higher concentrations after treatment, indicating that the process has to be
      further optimised to achieve satisfactory removal of all xenobiotic compounds.

PMID- 12188548
TI  - Treatment of winery wastewater by an anaerobic sequencing batch reactor.
AB  - Treatment of winery wastewater was investigated using an anaerobic sequencing
      batch reactor (ASBR). Biogas production rate was monitored and permitted the
      automation of the bioreactor by a simple control system. The reactor was operated
      at an organic loading rate (ORL) around 8.6 gCOD/L.d with soluble chemical oxygen
      demand (COD) removal efficiency greater than 98%, hydraulic retention time (HRT)
      of 2.2 d and a specific organic loading rate (SOLR) of 0.96 gCOD/gVSS.d. The
      kinetics of COD and VFA removal were investigated for winery wastewater and for
      simple compounds such as ethanol, which is a major component of winery effluent,
      and acetate, which is the main volatile fatty acid (VFA) produced. The comparison
      of the profiles obtained with the 3 substrates shows that, overall, the
      acidification of the organic matter and the methanisation of the VFA follow zero
      order reactions, in the operating conditions of our study. The effect on the gas
      production rate resulted in two level periods separated by a sharp break when the
      acidification stage was finished and only the breaking down of the VFA continued.

PMID- 12188549
TI  - Pilot-plant study on anaerobic treatment of a lipid- and protein-rich food
      industrial wastewater by a thermophilic multi-staged UASB reactor.
AB  - An on-site pilot-scale experiment was conducted to investigate the performance of
      a multi-staged UASB (MS-UASB) reactor by feeding with a food processing
      wastewater containing high strength of lipid and protein. The reactor was
      operated at a thermophilic condition (55 degrees C) for a period of 600 days. The
      reactor finally achieved 50 kgCOD.m(-3) d(-1) with a soluble COD removal of 90%
      (based on the influent total COD versus the effluent filtered COD), while the
      overall COD removal (based on the effluent COD-total) as considerably
      unsatisfactory at around only 60-70%. The presence of high strength of lipid and
      protein along with high concentration of Mg and Ca ions in the raw wastewater
      caused a severe scum and/or insolubilized substance formation within the UASB
      sludge bed, resulting in hindering the contact efficiency between substrate and
      sludge. The replacement of active microbial granules in the sludge bed with the
      insolubilized protein and lipid brought about deterioration of sludge
      methanogenic activity.

PMID- 12188550
TI  - Mesophilic and thermophilic anaerobic digestion of sulphate-containing
      wastewaters.
AB  - The effect of sulphate at an influent chemical oxygen demand (COD):sulphate ratio
      of 4 on the operational performance of anaerobic hybrid reactors treating
      molasses wastewater was investigated under mesophilic and thermophilic conditions
      in a long-term laboratory-scale study over a 1,081 day period. The presence of
      sulphate reduced the COD removal efficiency under both mesophilic and
      thermophilic conditions. At 55 degrees C, effluent acetate levels were
      consistently greater than 4000 mg l(-1) indicating that thermophilic acetate
      utilising methane-producing bacteria (MPB) or sulphate-reducing bacteria (SRB)
      had not developed in the reactor under the conditions applied. At 37 degrees C,
      acetate was exclusively utilised by acetoclastic methanogens, whereas H2
      utilising SRB predominated over H2-utilising MPB in the competition for hydrogen.
      By contrast, hydrogenotrophic MPB were shown to outcompete H2-utilising SRB
      during long-term thermophilic operation. 16SrDNA analysis of the seed sludge and
      reactor biomass on conclusion of the 37 degrees C and 55 degrees C trials
      illustrated that the dominant methanogen present on conclusion of the
      thermophilic trial in the absence of influent sulphate was related to
      Methanocorpusculum parvuum, and was capable of growth on both acetate and
      hydrogen. By contrast, an organism closely related to Methanobacterium
      thermoautotrophicum was the dominant methanogen present in the sulphate-fed
      reactor on completion of the thermophilic trial.

PMID- 12188551
TI  - Coliform and helminth eggs removal in a combined UASB reactor-baffled pond system
      in Brazil: performance evaluation and mathematical modelling.
AB  - The paper presents the monitoring results of a pilot UASB reactor followed by a
      baffled polishing pond treating domestic sewage in Brazil. Longitudinal profiles
      of E coli and helminth eggs along the baffled pond have been undertaken. The
      experimental results have been compared with von Sperling's model for coliform
      removal and Ayres' model for helminth eggs removal, and the fitting was
      considered satisfactory in both cases. The distribution of the helminth species
      along the system is also presented.

PMID- 12188552
TI  - Removal efficiency and methanogenic activity profiles in a pilot-scale UASB
      reactor treating settled sewage at moderate temperatures.
AB  - The performance of a sewage treatment system consisting of a settler followed by
      an Upflow Anaerobic Sludge Bed (UASB) reactor is described. Mean ambient and
      sewage temperature were 16.5 and 21.6 degrees C, respectively. Total Chemical
      Oxygen Demand (CODt) concentration averaged 224.2 and 152.6 mg/L, for raw and
      settled sewage, respectively. The effluent concentration was 68.5 mgCODt/L. Total
      and suspended COD removal efficiencies of approximately 70 and 80%, respectively,
      have been observed in the system at a mean Hydraulic Retention Time (HRT) of 2 +
      5 h. Maximum COD removal efficiency was achieved in the UASB reactor when upflow
      velocity (Vup) was 0.43 m/h (HRT = 6 h). Mean Specific Methanogenic Activity
      (SMA) and Volatile Suspended Solids (VSS) concentration in the granular sludge
      bed were 0.11 gCOD-CH4/gVSS.d and 30.0 gVSS/Lsludge, respectively. SMA was
      inversely related to VSS concentration, and both parameters varied along the
      sludge bed height. The Solids Retention Time (SRT) in the reactor was 450 days.
      Sludge characteristics have not been affected by changes of up to one month in
      Vup in the range 0.28-0.85 m/h (HRT 3-9 h). This system or two UASB reactors in
      series could be an alternative for sewage treatment under moderate temperature
      conditions.

PMID- 12188554
TI  - Early warning of disturbances in a laboratory-scale MSW biogas process.
AB  - The use of near-infrared spectroscopy (NIR) to monitorthe dynamics of a biogas
      process was evaluated using multivariate data analysis. The digester was a
      completely stirred 8 I tank reactor fed with the organic fraction of source
      sorted MSW. Intermittently the digester was overloaded with feed. Before and
      after overload on-line monitoring of NIR spectra and off-line analysis in the
      liquid and the gas phase of traditional chemical variables and microbial biomass,
      determined as total concentration of phospholipid fatty acids (PLFA and PLEL),
      were done. The dynamics that occurred due to overloading could be followed using
      principal component analysis of the obtained NIR-spectra. In addition, the
      response to changes in the digester fluid was reproducible and could be detected
      within five minutes, which can be considered as real-time monitoring. Selected
      wavelengths in the region 800-2,000 nm were used to make a PLS1 -regression with
      propionate. The regression resulted in a good correlation for propionate (R= 0.94
      and RMSEP of 0.21 g/l in the range of 0.3-3 g/l). The results indicate the
      possibility to develop an early warning biogas control system based on near
      infrared spectroscopy monitoring of propionate.

PMID- 12188553
TI  - A comparative analysis of a balance between the rates of polymer hydrolysis and
      acetoclastic methanogenesis during anaerobic digestion of solid waste.
AB  - A distributed model of anaerobic digestion of solid waste was developed. Waste,
      volatile fatty acids (VFA), methanogenic biomass and methane concentrations were
      the model variables. A system of parabolic partial differential equations in the
      one space variable and time with slab, cylindrical or spherical symmetry of the
      problem was solved numerically. Diffusion of VFA inhibiting both polymer
      hydrolysis and acetoclastic methanogenesis was taken into account. The model
      showed that concentration waves of methanogenic biomass and VFA propagated over
      reaction space. Diffusion-based "acceleration" of methane production in the
      reactor was possible when intensity of VFA utilisation in the methanogenic area
      was sufficient for complete digestion of incoming VFA. Otherwise, methanogenic
      area propagation would be suppressed. Optimum conditions for the solid waste
      digestion can be reached at low mass transfer at the beginning and at high mass
      transfer when methanogenic population increases. If the initial methanogenic
      biomass was localised at the centre of the reactor, the total reaction time was
      shorter as compared to the case when the initial biomass was uniformly
      distributed over the reactor volume. In the last case, there was no concentration
      wave propagation.

PMID- 12188555
TI  - A novel in-situ sampling and VFA sensor technique for anaerobic systems.
AB  - A key information for understanding and controlling the anaerobic biogas process
      is the concentration of Volatile Fatty Acids (VFA). However, access to this
      information has so far been limited to off-line measurements by manual time and
      labour consuming methods. We have developed a new technique that has made it
      possible to monitor VFA on-line in one of the most difficult media: animal slurry
      or manure. A novel in-situ filtration technique has made it possible to perform
      microfiltration inside the reactor system. This filter enables sampling from
      closed reactor systems without large scale pumping and filtering. Using this
      filtration technique together with commercially available membrane filters we
      have constructed a VFA sensor system that can perform automatic analysis on
      animal slurry at a frequency as high as every 15 minutes. The VFA sensor has been
      tested for a period of more than 60 days with more than 1000 samples on both a
      full-scale biogas plant and lab-scale reactors. The measuring range covers
      specific measurements of acetate, propionate, iso-/n-butyrate and iso-/n-valerate
      from 0.1 to 50 mM (6-3,000 mg).

PMID- 12188556
TI  - Removal of helminth eggs and fecal coliforms by anaerobic thermophilic sludge
      digestion.
AB  - Anaerobic digestion of two types of waste sludge was applied in order to assess
      the suitability of thermophilic conditions for the stabilization of organic
      matter and removal of fecal coliforms and helminth eggs. Feeding sludge was taken
      from an activated sludge municipal facility (BS) and from an enhanced primary
      treatment municipal plant (EPT). As an accompanying experiment, mesophilic
      digesters were also operated. The four digesters (M1, M2, T1, T2) had a 5 litre
      volume and an egg shape. A highly stabilized material was obtained at both
      temperatures with BS type of sludge, taking the reduction of volatile fraction of
      suspended solids (%Rvss) as indicator (84% for M1 and 74% for T1). In general,
      EPT sludge was a more difficult substrate, if compared with BS sludge;
      thermophilic condition was better adapted than mesophilic for this kind of
      sludge. Satisfactory reductions on counts of fecal coliforms and helminth eggs
      were achieved under thermophilic digestion for both types of feeding sludge. T1
      digester, fed with biological sludge, removed fecal coliforms below 1000 MPN/gTS
      and helminth eggs down to 0.28 HELarval/gTS, at an HRT of 20 days. As a general
      conclusion, anaerobic thermophilic digestion may be an appropriate option for
      sludge stabilization, in order to meet EPA Class A biosolids final disposal
      regulations. However, further research is needed in order to consistently remove
      helminth eggs and fecal coliforms from waste sludge at shorter hydraulic
      retention times.

PMID- 12188557
TI  - Evaluation of thermophilic anaerobic microbial consortia using fluorescence in
      situ hybridization (FISH).
AB  - In this study we investigated the development of anaerobic biofilms in
      differential reactors and suspension cultures in batch reactors under
      thermophilic (55 degrees C) conditions. FISH, SEM, chemical and chromatographic
      analysis were used. The differential reactors reached 99.6%, 92.3% and 6.7% of
      acetic acid, COD and sulfate removal efficiencies, respectively, after 166 h of
      incubation time. The batch reactor reached 95.6% and 31.8% of acetic acid and
      sulfate removal efficiencies after 675 h, respectively. FISH results showed that
      bacterial cells rather than archaeal cells dominated biofilms. These cells,
      detected with the Bacteria specific probe (EUB338), accounted for 61.1% (+/-3.6)
      of the DAPI-stained cells and resembled acetate-oxidizing rods and
      Desulfotomaculum morphologies. Archaeal cells, which hybridized to the Archaea
      specific probe (ARC915), were also detected in biofilm but they accounted for
      36.7% (+/-2.9) of the DAPI-stained cells. These cells were similar to
      Methanosaeta-like and hydrogenotrophic methanogen rods. In the suspension
      culture, archaeal cells (58.0%+/-3.8) morphologically similar to Methanosarcina
      and hydrogenotrophic methanogen rods were predominant over bacterial cells
      (41.0%+/-4.5), which resembled acetate-oxidizing rods and Desulfotomaculum
      morphologies. The percentage of sulfate-reducing bacteria cells (SRB) ranged from
      12.2% (+/-2.5) to 21.7% (+/-2.8) in the biofilms and from 13.3% (+/-3.6) to 21.7%
      (+/-4.3) of the DAPI stained cells in suspension culture.

PMID- 12188558
TI  - Co-digestion of energy crops and industrial confectionery by-products with cow
      manure: batch-scale and farm-scale evaluation.
AB  - The possible co-digestion of energy crops and industrial confectionery by
      products with cow manure was evaluated firstly, through long-term batch
      experiments and secondly, in a farm-scale digester. In batch assays, digestion
      with mesophilically digested cow manure as inoculum resulted in specific methane
      yields (m3 kg(-1) VS added waste) of 0.35 for grass hay (particle size <1.0 cm);
      0.26 for oats (0.5 cm) and 0.21 for clover (2.0 cm) harvested at vegetative stage
      and 0.14 (2.0 cm) for clover harvested at flowering stage. Specific methane
      yields (m3 kg(-1) VS added waste) for confectionery by-products were 0.37 for
      chocolate, 0.39 for black candy and 0.32 for confectionery raw material. Out the
      three particle sizes (2.0, 1.0 and 0.5 cm) tested, particle size of 1.0 cm was
      found ideal for digestion of grass hay and clover while, particle size reduction
      did not influence methane production from oats. Stage of the crop influenced the
      methane yields, with clover harvested at vegetative stage yielding 33% higher
      methane than when harvested at flowering stage. An approximate 60% enhancement in
      methane yield was noticed with the co-digestion of industrial confectionery
      wastes with cow manure in a full-scale farm digester.

PMID- 12188559
TI  - Co-digestion of domestic kitchen waste and night soil sludge in a full-scale
      sludge treatment plant.
AB  - A study was made on the domestic kitchen waste and night soil treatment
      performance of a full-scale sludge treatment plant. The sludge treatment at this
      plant was by thermophilic methane fermentation. The initial treatment, mesophilic
      to thermophilic fermentation, was able to be started up within a short time by
      adjusting the amount of influent waste. Thermophilic methane fermentation was
      carried out for five months (May-October) and the performance under a mean
      residual time of 22 days indicated a VTS decomposition of 42%, gas generation of
      54-1,610 m3/day (average: 755 m3/day), and a mean methane concentration of 60%.
      The methane gas was used to generate power in the plant and the amount of power
      generated by methane gas was highest in October (average of 1,200 kWh/day). This
      was equivalent to about 7% of the power consumed at the entire sludge treatment
      plant. The BOD/NH4-N of the activated sludge influent water was lower, compared
      to a case where there is no recycle flow, due to the recycle flow from the
      methane fermentation process. There was, therefore, a tendency for an increase in
      the amount of methanol charged into the secondary denitrification tank. However,
      the quality of the effluent was satisfactory (BOD< 10 mg/L, SS< 5 mg/L, and T-N<
      25 mg/L). Study results indicated that it was possible to implement a full-scale
      plant for recovering organic waste.

PMID- 12188560
TI  - Sulfate disinfection, stabilisation and heavy metal removal from sewage sludge-
      process description and preliminary results.
AB  - A new, closed loop process for the disinfection, stabilisation and removal of
      heavy metal from sewage sludge (consisting of a sludge/sulfuric acid reactor,
      hybrid H2S generator and H2S bioscrubber) is described. Preliminary results for
      total solids (TS), volatile suspended solids (VSS), chemical oxygen demand (COD),
      acetate and propionate destruction in the hybrid H2S generator have shown that
      digestion efficiency is not compromised in a hybrid reactor generating H2S
      compared to a methanogenic reactor. 70% of the electron flow in the hybrid H2S
      generator was diverted to methane at a COD:SO4 ratio of 5.45:1. Enough H2SO4
      could be generated from the H2S emitted at this ratio to effect sufficient metal
      solubilisation and pathogen removal from primary sludge.

PMID- 12188561
TI  - State of the art and future perspectives of thermophilic anaerobic digestion.
AB  - The state of the art of thermophilic digestion is discussed. Thermophilic
      digestion is a well established technology in Europe for treatment of mixtures of
      waste in common large scale biogas plants or for treatment of the organic
      fraction of municipal solid waste. Due to a large number of failures over time
      with thermophilic digestion of sewage sludge this process has lost its appeal in
      the USA. New demands on sanitation of biosolids before land use will, however,
      bring the attention back to the use of elevated temperatures during sludge
      stabilization. In the paper we show how the use of a start-up strategy based on
      the actual activity of key microbes can be used to ensure proper and fast
      transfer of mesophilic digesters into thermophilic operation. Extreme
      thermophilic temperatures of 65 degrees C or more may be necessary in the future
      to meet the demands for full sanitation of the waste material before final
      disposal. We show data of anaerobic digestion at extreme thermophilic
      temperatures.

PMID- 12188562
TI  - Using a UASB reactor for thickening and digestion of discharged sludge from
      submerged aerated biofilters.
AB  - Results from one year of experimental monitoring the wastewater treatment plant
      of UFES (Federal University of Espirito Santo) treating a residential urban area
      of city of Vitoria ES, Brazil, have shown a good performance by a UASB reactor as
      a part of domestic sewage treatment and also performing aerobic sludge thickening
      and digestion. The total solids concentration around 6% was obtained in main
      sludge blanket at bottom of reactor despite a high daily aerobic sludge load
      discharged from four aerobic submerged biofilters containing 0.4% TS and 80% of
      VS/TS. Similar values were found in another experimental period when the reactor
      was fed only with raw domestic sewage. The average removal efficiency of organic
      matter and suspended solids observed for domestic sewage treatment are around 63%
      of SS and 64% COD. These results were obtained in the UASB reactor working with
      or without aerobic sludge recycling, with constant or variable load and hydraulic
      detention time (HDT) less than 6 hours. A proposed mass balance allows a
      theoretical assessment of aerobic sludge digestion and accumulation into UASB
      reactor.

PMID- 12188563
TI  - Measuring metal and phosphorus speciation in P-rich anaerobic digesters.
AB  - High concentrations of soluble orthophosphate, magnesium and potassium are
      released during anaerobic digestion of biological phosphorus removal (BPR)
      sludge. This research was undertaken to investigate the effects of phosphorus
      enrichment on digester performance, metal and phosphorus speciation. High
      concentrations of soluble PO4-P (> 250 mg/l) were found to have a retarding
      effect on anaerobic digestion, reducing the rate of volatile solids digestion and
      methane production in comparison to control digesters. This was found to be
      reversible after a period of time, which was related to the amount of PO4-P added
      to the digesters, higher concentrations of PO4-P requiring more time for digester
      recovery. Addition of magnesium and potassium to the digesters, together with PO4
      P, reduced the inhibitory effect of phosphorus enrichment but these digesters
      still showed lower rates of volatile solids digestion and methane production in
      comparison to the control digesters. Phosphorus enrichment resulted in extensive
      precipitation of calcium, magnesium and manganese, markedly reducing the soluble
      and easily available fractions of these metals. Other trace metals such as
      copper, zinc, chromium, nickel and cobalt actually showed increased levels of
      solubility as a result of phosphorus enrichment. This was thought to be caused by
      high levels of soluble organic carbon in the phosphorus-rich anaerobic digesters,
      which acted as organic ligands for metal complexation.

PMID- 12188564
TI  - Novel anaerobic process for the recovery of methane and compost from food waste.
AB  - Multi-step sequential batch two-phase anaerobic composting (MUSTAC) process was
      used to recover methane and composted material from food waste. The MUSTAC
      process consists of five leaching beds for hydrolysis, acidification and post
      treatment, and an upflow anaerobic sludge blanket (UASB) reactor for methane
      recovery. This process involves the combined methods of sequential batch
      operation and two-phase anaerobic digestion for simple operation and high
      efficiency. Rumen microorganisms are inoculated due to their enhanced
      cellulolytic activity. Each leaching bed is operated in a sequential batch mode.
      Five leaching beds are operated in a multi-step mode with a two-day interval
      between degradation stages. Acidified products in the leachate from the leaching
      beds are converted to methane in the UASB reactor. The MUSTAC process
      demonstrated that it was capable of removing 84.9% of volatile solids (VS) and
      converting 85.6% of biochemical methane potential (BMP) into methane at 10.9 kg
      VS/m3 x d in 10 days. Methane gas production rate was 2.31 m3/m3 x d. The output
      from the post-treatment of residues in the same leaching bed without troublesome
      moving met the Korean regulation on compost, indicating that it could be used for
      soil amendment.

PMID- 12188565
TI  - Anaerobic digestion for sustainable development: a natural approach.
AB  - After the discovery of methane gas by Alessandro Volta in 1776, it took about 100
      years before anaerobic processes for the treatment of wastewater and sludges were
      introduced. The development of high rate anaerobic digesters for the treatment of
      sewage and industrial wastewater took until the nineteen-seventies and for solid
      waste even till the nineteen-eighties. All digesters have in common that they
      apply natural anaerobic consortia of microorganisms for degradation and
      transformation processes. In view of this, it could be rewarding to evaluate the
      efficiency of natural ecosystems for their possible application. Examples of high
      rate anaerobic natural systems include the forestomach of ruminants and the
      hindgut of certain insects, such as termites and cockroaches. These 'natural
      reactors' exhibit volumetric methane production rates as high as 35 l/l.d. The
      development of anaerobic reactors based on such natural anaerobic systems could
      produce eco-technologies for the effective management of a wide variety of solid
      wastes and industrial wastewater. Important limitations of anaerobic treatment of
      domestic sewage relate to the absence of nutrient and pathogen removal. A
      combination of anaerobic pre-treatment followed by photosynthetic posttreatment
      is proposed for the effective recovery of energy and nutrients from sewage. This
      eco-technology approach is based on the recognition that the main nutrient
      assimilating capacity is housed in photosynthetic plants. The proposed anaerobic
      photosynthetic process is energy efficient, cost effective and applicable under a
      wide variety of rural and urban conditions. IN CONCLUSION: a natural systems
      approach towards waste management could generate affordable eco-technologies for
      effective treatment and resource recovery.

PMID- 12188566
TI  - Combining UASB technology and advanced oxidation processes (AOPs) to treat food
      processing wastewaters.
AB  - UASB treatment of fruit cannery and winery effluents was shown to be feasible.
      However, the treated effluents still have residual COD levels well above the
      legal limit of 75 mg.l(-1) for direct discharge to a water system and a form of
      post-treatment is necessary to reduce the COD further. Ozone and ozone/hydrogen
      peroxide were used in combination with a granular activated carbon contacting
      column to assess the effectiveness as a post-treatment option for the UASB
      treated fruit cannery and winery effluent. Colour reduction in the effluents
      ranged from 66 to 90% and COD reductions of 27-55% were achieved. The combination
      of ozone and hydrogen peroxide gave better results than ozonation alone.
      Significant progress was thus made in achieving the legal limit of 75 mg.l(-1).

PMID- 12188567
TI  - Adaptation of the methanogenic granules to denitrification in anaerobic-anoxic
      USSB reactor.
AB  - Continuous laboratory experiments have confirmed that the construction of the
      USSB reactor was suitable for the combination of several biological wastewater
      treatment processes and that both anaerobic and denitrifying anoxic granules
      could be cultivated inside a compact reactor. The anoxic granules were
      transformed from the anaerobic granules after the shift from anaerobic to anoxic
      conditions in the upper compartments of the USSB reactor. The denitrification in
      such a system can be very intensive and efficient because of the high
      concentration of the sludge in anoxic compartments, and the high activity of the
      sludge due to a high and stable temperature. The denitrification rate of 62 mg
      N/l.h (at 35 degrees C) was achieved in spite of COD-limited conditions in the
      anoxic compartment of the USSB reactor. Maximum specific activity of anoxic
      granules 47 mg N/g VSS.h (at 35 degrees C, with glucose as substrate) was found
      in batch tests. The anoxic granules originating from the anaerobic granules have
      still demonstrated a significant methanogenic activity comparable with the
      anaerobic granules.

PMID- 12188568
TI  - Controlling calcium precipitation in an integrated anaerobic-aerobic treatment
      system of a "zero-discharge" paper mill.
AB  - The pulp and paper industry uses significant amounts of water and energy for the
      paper production process. Closing the water cycles in this industry, therefore,
      promises large benefits for the environment and has the potential of huge cost
      savings for the industry. Closing the water cycle on the other hand also
      introduces problems with process water quality, quality of the end-product and
      scaling, owing to increased water contamination. An inline treatment system is
      discussed in which anaerobic-aerobic bioreactors perform a central role for
      removing both organic and inorganic pollutants from the process water cycle. In
      the proposed set-up, the organic compounds are converted to methane gas and
      reused for energy supply, while sulphur compounds are stripped from the process
      cycle and calcium carbonate is removed by precipitation. Improved control of the
      treatment system will direct the inorganic precipitates to a location where it
      does not adversely affect paper production and process water treatment. A
      simulation program for triggering and controlling CaCO3 precipitation was
      developed that takes both biological conversions and all relevant chemical
      equilibria in the system into account. Simulation results are in good agreement
      with data gathered in a full-scale "zero-emission" paper plant and indicate that
      control of CaCO3 precipitation can be improved, e.g. in the aerobic post
      treatment. Alternatively, a separate precipitation unit could be considered.

PMID- 12188569
TI  - Autotrophic denitrification for combined hydrogen sulfide removal from biogas and
      post-denitrification.
AB  - In this paper we describe an alternative flow-chart for full treatment of
      wastewaters rich in organic substrates, ammonia (or organic nitrogen), and
      sulfate, such as those generated in fish cannery industries. Biogas generated
      during anaerobic pretreatment of these wastewaters is rich in hydrogen sulfide
      that needs to be removed to enable application of the biogas. Nitrogen
      elimination is traditionally achieved by subsequent nitrification and
      denitrification of the effluent of the anaerobic reactor. Alternatively, the
      hydrogen sulfide in the biogas can be applied as an electron donor in an
      autotrophic post-denitrification step. In order to study whether sufficient
      hydrogen sulfide containing biogas for denitrification was produced in the
      anaerobic reactor, the biogas composition as a function of the anaerobic reactor
      pH was estimated based on a typical wastewater composition and chemical
      equilibrium equations. It is demonstrated that typical sulfate and nitrogen
      concentrations in fish cannery wastewater are highly appropriate for application
      of autotrophic post-denitrification. A literature review furthermore suggested
      that the kinetic parameters for autotrophic denitrification by Thiobacillus
      denitrificans represent no bottleneck for its application. Initial experimental
      studies in fixed-film reactors were conducted with sodium sulfide and nitrate as
      an electron donor-acceptor couple. The results revealed that only moderate
      volumetric treatment capacities (< 1 g-NO3- N l(-1) day(-1)) could be achieved.
      Mass balances suggested that incomplete sulfide oxidation to elemental sulfur
      occurred, limiting biomass retention and the treatment capacity of the reactor.
      Future research should clarify the questions concerning product formation from
      sulfide oxidation.

PMID- 12188570
TI  - Strategies for augmenting the pentachlorophenol degradation potential of UASB
      anaerobic granules.
AB  - Anaerobic degradation of pentachlorophenol (PCP) is an example of a process that
      may benefit from enrichment or bioaugmentation. In one approach, enrichment
      acceleration was attempted by applying an on-line control-based selective stress
      strategy to a native anaerobic upflow sludge bed (UASB) system; this strategy
      linked PCP loading rate to methane production. As a result, the reactor biomass
      potential for PCP complete dechlorination reached a rate of 4 mg g(-1) volatile
      suspended solid (VSS) day(-1) within a period of 120 days. In another approach, a
      pure culture, Desulfitobacterium frappieri PCP-1, a strictly anaerobic Gram
      positive bacterium, was used to augment the granular biomass of the UASB reactor.
      This also resulted in a specific degradation rate of 4 mg PCPg(-1) VSS day(-1);
      however, this potential was attained within 56 days. Fluorescent in situ
      hybridization (FISH) showed that the PCP-1 strain was able to rapidly attach to
      the granule and densely colonize the outer biofilm layer.

PMID- 12188572
TI  - Sludge bed development in denitrifying reactors using different inocula
      performance and microbiological aspects.
AB  - Aerobic and methanogenic consortia were evaluated as inocula for laboratory scale
      denitrifying reactors, fed with a synthetic wastewater with acetate as the main
      electron donor. The denitrifying microflora of inocula and reactors was evaluated
      by specific denitrifying activity, enumeration and isolation of denitrifiers,
      which were screened by amplified ribosomal DNA restriction analysis. Reactor
      performance was monitored by COD and nitrate removal efficiencies and granule
      size. The aerobic sludge failed to form granules, probably due to the development
      of a filamentous, nitrate-reducing organism which was characterised by 16SrDNA
      sequencing as Bacillus cereus. The methanogenic sludge showed denitrifying
      activity and adapted very rapidly to denitrifying conditions in the two reactors
      seeded with granules of different sizes. Denitrifiers grew around the granules,
      increasing the specific denitrifying activity of the sludge over 10-fold.
      Exopolymer-forming organisms, belonging to the same species, were isolated from
      both reactors. Granule size increased during operation, but flotation of the
      aggregates, related to gas retention was observed.

PMID- 12188573
TI  - Treatment of anaerobically treated domestic wastewater using rotating biological
      contactor.
AB  - A small-scale pilot plant consisting of a three-stage RBC has been investigated
      for the removal of E. coli, COD fractions and ammonia from the effluent of an
      UASB reactor treating domestic wastewater. The results obtained reveal that a
      three-stage system operated at a HRT of 3.0 h represents an effective
      posttreatment process. The remaining COD in the final effluent was only 51 (+/-
      7) mgl(-1). Ammonia concentration was reduced by 67 (+/- 7.6) %. The overall E.
      coli reduction was 1.39 log10 at an influent count of 6.5 log10 corresponding to
      an overall removal efficiency of 95.8 (+/- 4.7) %. However, according to
      prevailing standards, residual E. coli counts are still high for unrestricted
      reuse for irrigation purposes. When the system was operated at a HRT of 10 h,
      overall E. coli removal and ammonia reduction were 99.9 (+/- 0.05)% and 92 (+/-
      6.5) % respectively. At a HRT of 10 h, recirculation of the 3rd stage effluent to
      the 1st stage reduced the residual of E. coli in the final effluent from 2 x
      10(3) to 9.8 x 10(2)/100ml. Moreover, the recirculation of nitrified effluent
      from the 3rd stage to the 1st stage increased ammonia removal in the stage 1 from
      23 to 43%. This relatively high ammonia removal likely can be attributed to the
      supply of nitrifiers from 3rd stage to the 1st one.

PMID- 12188571
TI  - Oxygen-limited nitrogen removal in a lab-scale rotating biological contactor
      treating an ammonium-rich wastewater.
AB  - A lab-scale Rotating Biological Contactor (RBC) was operated with the purpose of
      oxygen-limited (autotrophic) nitrification-denitrification of an ammonium-rich
      synthetic wastewater without Chemical Oxygen Demand (COD). Based on the field
      observations that RBCs receiving anaerobic effluents come to anoxic ammonium
      removal, the RBC was inoculated with methanogenic sludge. Some 100 days after the
      addition of the anaerobic sludge to the reactor as a possible means of a rapid
      initiation of the nitrogen (N) removal process, a maximum ammonium removal of
      1,550 mg N m(-2) d(-1) was achieved. Batch tests with 15N labeled ammonium and
      nitrite indicated that a large part of that N was removed via oxygen-limited
      oxidation of ammonium with nitrite as the electron acceptor. The other part was
      removed via conventional denitrification, presumably with COD released from lysis
      of cells. Species identification of the most abundant microorganisms revealed
      that Nitrosomonas spp. were the dominant ammonium-oxidizers in the sludge. Thus
      far, the molecular characterization of the sludge could not show the presence of
      Planctomycetes among the most dominant species. Overall this experiment confirms
      the property of the RBC system to remove ammonium to nitrogen gas without the use
      of heterotrophic carbon source.

PMID- 12188574
TI  - Effect of carbon dioxide and ammonium removal on pH changes in polishing ponds.
AB  - If nutrient removal is to be obtained in ponds treating sewage, the pH must be
      raised so that ammonia can desorb and phosphates can precipitate. In this paper
      it is shown that the pH increase in ponds can be predicted quantitatively from
      simple stoichiometry, taking into consideration physical and biological carbon
      dioxide removal, ammonia stripping and calcium carbonate precipitation.
      Biological CO2 removal by photosynthesis is identified as the main process to
      effect pH increase in ponds. The rate of pH increase and consequently the
      required retention time depend on the net rate of CO2 consumption, the extent of
      ammonium stripping, the characteristics of the influent (alkalinity and pH) as
      well as factors concerning the environment (temperature) and dimensions (depth)
      of the pond. A high pH (range 9 to 10) can be obtained in about 5 days if
      digested sewage is used (low organic material concentration), climate conditions
      are favourable and the pond is shallow (< 0.5 m deep).

PMID- 12188575
TI  - Reductive biodegradation of 1,2-dichloroethane by methanogenic granular sludge:
      perspectives for in situ remediation.
AB  - Granular methanogenic sludge was able to dechlorinate 1,2-dichloroethane (1,2
      DCA) to ethene in UASB reactors. Ethanol served as the sole carbon and energy
      source. The average dechlorination rate measured on the basis of ethene
      production varied between 1.7 and 2.1 micromol 1,2-DCA/(h.gVSS) (46.7 and 57.4
      mg/L.d). In order to elucidate the microbial origin of this bioconversion,
      enrichment cultures of the methanogenic sludge were prepared with different
      carbon and electron sources: pyruvate, lactate, H2/CO2, ethanol and formate.
      Dithiothreitol (DTT) was the strong reductant in order to increase the negative
      redox potential in the media. A homo-acetogenic gram-positive strain could be
      isolated in the presence of formate. 16S rRNA of the isolated strain showed that
      the bacterium was closely related (99.7%) to Acetobacterium wieringae. The strain
      also grew on pyruvate, lactate, H2/CO2 and ethanol, although dechlorination rates
      of 1,2-DCA were at least 5 times higher when formate was the (only) electron
      source. Average conversion rates reached 3 micromol/(h.g(dry cells)) and appeared
      t relate to cometabolic biocatalysis on the corrinoid centers of the homo
      acetogenic strain. Some perspectives of anaerobic in situ bioremediation of
      groundwater polluted with chloroethanes are presented.

PMID- 12188576
TI  - Influence of electron donors and acceptors on the bioremediation of soil
      contaminated with trichloroethene and nickel: laboratory- and pilot-scale study.
AB  - Laboratory- and pilot-scale studies were conducted in order to adjust and
      optimize the in-situ conditions for bioremediation of a soil contaminated with
      trichlororethene (TCE) and nickel. Results from laboratory studies showed that
      the indigenous microorganisms of the soil were limited by the type of electron
      donor. A better TCE dechlorination was obtained when the electron donor was
      composed of a mixture of methanol and lactate, as compared to that with methanol
      alone. Addition of up to 10 mM of sulphate as external electron acceptor (in
      combination with TCE) and with a mixture of methanol and lactate as electron
      donor had no significant effect on the TCE reducing activity of indigenous
      microorganisms of the soil, while higher concentrations (15 and 20 mM) yielded a
      lower dechlorination. Long term operation of a large pilot-scale soil reactor
      demonstrated the feasibility of a single-process in situ soil remediation.
      Results showed that, on one hand, TCE was progressively and stepwise reduced to
      cis-dichloroethene (DCE), vinyl chloride (VC) and finally to ethene, using only
      the indigenous microorganisms of the soil. On the other hand, stimulating the
      activity of sulphate-reducing bacteria of the soil with the addition of sulphate
      as electron acceptor was efficient in precipitating nickel as nickel sulphide.

PMID- 12188577
TI  - Microbial cycling of volatile organic sulfur compounds in anoxic environments.
AB  - Microbial cycling of volatile organic sulfur compounds (VOSC) is investigated due
      to the impact these compounds are thought to have on environmental processes like
      global temperature control, acid precipitation and the global sulfur cycle.
      Moreover, in several kinds of industries like composting plants and the paper
      industry VOSC are released causing odor problems. Waste streams containing these
      compounds must be treated in order to avoid the release of these compounds to the
      atmosphere. This paper describes the general mechanisms for the production and
      degradation of methanethiol (MT) and dimethyl sulfide (DMS), two ubiquitous VOSC
      in anaerobic environments. Slurry incubations indicated that methylation of
      sulfide and MT resulting in MT and DMS, respectively, is one of the major
      mechanisms for VOSC in sulfide-rich anaerobic environments. An anaerobic
      bacterium that is responsible for the formation of MT and DMS through the
      anaerobic methylation of H2S and MT was isolated from a freshwater pond after
      enrichment with syringate as a methyl group donating compound and sole carbon
      source. In spite of the continuous formation of MT and DMS, steady state
      concentrations are generally very low. This is due to the microbial degradation
      of these compounds. Experiments with sulfate-rich and sulfate-amended sediment
      slurries demonstrated that besides methanogens, sulfate-reducing bacteria can
      also degrade MT and DMS, provided that sulfate is available. A methanogen was
      isolated that is able to grow on DMS as the sole carbon source. A large survey of
      sediments slurries of various origin demonstrated that both isolates are commonly
      occurring inhabitants of anaerobic environments.

PMID- 12188578
TI  - The influence of experimental conditions on the assessment of the toxicity of 2,4
      dichlorophenol to anaerobic degradative bacteria.
AB  - The toxicity of 2,4-dichlorophenol (2,4-DCP) to anaerobic bacteria in refuse
      cultures was investigated at two temperatures (30 and 37 degrees C) and after two
      different exposure periods to the toxicants. It was shown that at 0.52mM 2,4-DCP
      the time of exposure of microorganisms to 2,4-DCP affected the relative activity
      (Av) of the production of methane. Av values at the beginning of the steady-state
      phase were lower than those recorded two weeks later. The incubation temperature
      selected also critically affected the assessment of anaerobic toxicity; at 37
      degrees C an imbalance of the activities of fermentative bacteria and acetogens
      with those of methanogens was observed.

PMID- 12188579
TI  - The IWA Anaerobic Digestion Model No 1 (ADM1).
AB  - The IWA Anaerobic Digestion Modelling Task Group was established in 1997 at the
      8th World Congress on Anaerobic Digestion (Sendai, Japan) with the goal of
      developing a generalised anaerobic digestion model. The structured model includes
      multiple steps describing biochemical as well as physicochemical processes. The
      biochemical steps include disintegration from homogeneous particulates to
      carbohydrates, proteins and lipids; extracellular hydrolysis of these particulate
      substrates to sugars, amino acids, and long chain fatty acids (LCFA),
      respectively; acidogenesis from sugars and amino acids to volatile fatty acids
      (VFAs) and hydrogen; acetogenesis of LCFA and VFAs to acetate; and separate
      methanogenesis steps from acetate and hydrogen/CO2. The physico-chemical
      equations describe ion association and dissociation, and gas-liquid transfer.
      Implemented as a differential and algebraic equation (DAE) set, there are 26
      dynamic state concentration variables, and 8 implicit algebraic variables per
      reactor vessel or element. Implemented as differential equations (DE) only, there
      are 32 dynamic concentration state variables.

PMID- 12188580
TI  - Competition for H2 between sulfate reducers, methanogens and homoacetogens in a
      gas-lift reactor.
AB  - Reported values for growth kinetic parameters show an order in competitivity of
      heterotrophic sulfate reducing bacteria>methanogens>homoacetogens for the
      substrate hydrogen. This order suggests that methanogens can succesfully compete
      with consortia of heterotrophic SRB and homoacetogens when H2/CO2 is present as
      sole substrate. However, we found in experiments using gas-lift reactors
      inoculated with anaerobic sludge and fed with H2/CO2 and sulfate, that
      heterotrophic sulfate reduction rapidly and completely outcompeted
      methanogenesis, whereas a low amount of acetate was formed. Thus, in disagreement
      with the above competitivity order, hydrogen is more readily consumed by
      homoacetogenesis than by methanogenesis, indicating that the competition is not
      kinetically determined. The superior settling velocity of sulfidogenic-acetogenic
      sludge compared to that of methanogenic sludge suggests that the former sludge is
      better retained, which can explain the predominance of sulfate
      reduction/homoacetogenesis over methanogenesis.

PMID- 12188581
TI  - Simulation of a periodic anaerobic baffled reactor (PABR): steady state and
      dynamic response.
AB  - The Periodic Anaerobic Baffled Reactor (PABR) is a novel high-rate configuration
      for wastewater treatment. The reactor resembles an ABR with the compartments
      arranged in a circular manner. The feeding and effluent points are periodically
      set in different compartments by proper manipulation of valves that determine the
      flow pattern. This way of feeding makes the reactor response oscillating and
      gives the PABR a great flexibility in the operation mode. A 15 litre PABR was
      operated on a gelatin based medium under steady and variable organic loading
      rate. The experimental conditions were simulated using a mathematical model whose
      primary feature was that each compartment was considered as a two-section tank,
      each section with a different biomass concentration in them. The degree of
      biomass accumulation was determined indirectly by the operating conditions and
      the reactor dynamics and was not set a-priori.

PMID- 12188582
TI  - A new model for anaerobic processes of up-flow anaerobic sludge blanket reactors
      based on cellular automata.
AB  - The advantageous performance of the UASB reactors is due to the immobilisation of
      the active biomass, since bacteria coagulate forming aggregates usually called
      granules. Changes in organic loading rate, hydraulic loading rate or influent
      substrate composition usually result in changes in granule characteristics and
      lead to different reactor behaviour. A dynamic mathematical model has been
      developed for the anaerobic digestion of a glucose based synthetic wastewater in
      UASB reactors. Cellular automata (CA) theory has been applied to simulate the
      granule development process. The model takes into consideration that granule
      diameter and granule microbial composition are functions of the reactor
      operational parameters and is capable of predicting the UASB performance and the
      layer structure of the granules.

PMID- 12188583
TI  - Limits of anaerobic biodegradation.
AB  - The main factors responsible for anaerobic recalcitrance are reviewed. Anaerobic
      recalcitrance is associated with hydrocarbons lacking functional groups, branched
      molecules (gasoline oxygenates), aromatic amines and aromatic sulfonates. The
      most recalcitrant compounds are high molecular weight nonhydrolyzable polymers
      such as plastic, lignin and humus, which cannot be taken up by cells. Recently
      new capabilities of anaerobic microorganisms have been discovered to degrade
      compounds previously considered to be recalcitrant. For example, anaerobic
      bacteria initiate the degradation of alkylbenzenes and alkanes with an unusual
      addition reaction with fumarate, forming a hydrocarbon-succinate adduct. Finally,
      new evidence indicates that the most recalcitrant compounds (humic substances)
      are not so inert and can play important roles in aiding the biodegradation of
      other compounds by serving as an electron acceptor or redox mediator.

PMID- 12188584
TI  - Modelling the competition between sulphate reducers and methanogens in a
      thermophilic methanol-fed bioreactor.
AB  - Sulphate can be removed from wastewater by means of biological anaerobic
      reduction to sulphide. The reduction requires the presence of a substrate that
      can serve as an electron donor. Methanol a suitable electron donor for sulphate
      reduction under thermophilic conditions. In an anaerobic system containing
      methanol and sulphate, acetogenic bacteria (AB) and methanogenic archaea (MA)
      compete with sulphate reducing bacteria (SRB) for methanol or its degradation
      intermediates. Previously obtained results indicate that at 65 degrees C SRB and
      MA mainly compete for the intermediate hydrogen instead of methanol. For
      efficient use of methanol as electron donor for sulphate reduction it is
      important that for the treatment of sulphate wastewater in an anaerobic reactor
      SRB out-compete MA. The mechanisms that determine the outcome of the competition
      are, however, not well understood. This paper describes a model based on growth
      kinetics of methanol-oxidising AB, and hydrogen-consuming SRB and MA, that can
      describe the competition between SRB and MA in a methanol-fed bioreactor. We
      present the model and its calibration using experimental data, and we discuss its
      shortcomings and suggest possible improvements.

PMID- 12188585
TI  - Hydrolysis kinetics of dissolved polymer substrates.
AB  - In this paper, the relation between the hydrolysis rate of dissolved polymer
      substrates and sludge concentration was investigated in two ways, viz. by
      laboratory experiments and by computer simulations. In the simulations, the
      hydrolysis of dissolved polymer components was regarded as a general
      depolymerisation process in which the bonds of the parent molecule break randomly
      until only monomer and dimer components remain. The results illustrate that for
      the hydrolysis of dissolved polymer substrates the enzyme activity is the rate
      limiting factor. Moreover, a general depolymerisation process can describe the
      enzymatic hydrolysis of these components.

PMID- 12188586
TI  - Attentional bias and alcohol dependence: a controlled study using the modified
      stroop paradigm.
AB  - Detoxified clients at an alcohol treatment centre (n = 34) were administered a
      modified Stroop test, an index of attentional bias or distraction. Their
      performance was compared to controls (n = 33) who were staff recruited from
      specialist substance misuse clinics based on the presumption of familiarity with
      the alcohol and addiction related terms of the Stroop task. The card-format
      Stroop test contained words such as "alcohol" and "relapse" and neutral,
      semantically homogenous words such as "table" and "chair." Analysis of variance
      (ANOVA) revealed significant main effects for word type with both the clinic
      attendees and controls taking longer to colour-name alcohol-related words.
      Predicted interactions between word type and subject status were not observed.
      These findings suggest that both problem drinkers and clinic staff did not differ
      significantly in the degree of Stroop interference displayed, although a trend
      towards greater distraction by clinic attendees with alcohol-related terms was
      noted. The statistically significant results were nonetheless consistent with
      findings that expertise or familiarity can be influential factors in Stroop
      performance. Multiple regression analyses with the entire sample (n = 65) showed
      that psychometric and self-reported indices of alcohol dependence and consumption
      were predictive of Stroop interference. This is consistent with the existence of
      a acquired information processing bias related to escalating alcohol use and
      dependence such as that proposed by Tiffany [Psychol. Rev. 97 (1990) 147.].

PMID- 12188587
TI  - Relationship between problem gambling and substance use in a methadone
      maintenance population.
AB  - Few studies have examined the relationship between pathological gambling and
      substance abuse treatment outcome. This study assessed the gambling behavior of
      62 patients enrolled in a methadone maintenance treatment program. Eleven (17.7%)
      met current SOGS criteria for probable pathological gambling. Patients with and
      without probable pathological gambling were compared on substance abuse treatment
      outcome measures including urine toxicology results for heroin and cocaine use,
      and clinic dropout. Results indicated that those who were probable pathological
      gamblers were more likely to use cocaine through therapy, and more likely to drop
      out of the clinic treatment program than nonpathological gamblers. Implications
      for substance abuse treatment are discussed.

PMID- 12188588
TI  - Bupropion for pharmacologic relapse prevention to smoking: predictors of outcome.
AB  - The aim of this study was to identify predictors of successful relapse prevention
      in smokers receiving long-term sustained-release bupropion. Smokers (N= 784) who
      were interested in stopping smoking were enrolled in a 7-week, open-label
      bupropion phase. Abstinent subjects at the end of treatment and eligible to
      proceed (N= 429) were randomized to active bupropion or placebo through Week 52
      and then followed for an additional year. The best overall predictor of less
      relapse to smoking was assignment to active bupropion. In aggregate, the results
      indicate that bupropion can be prescribed to diverse populations of smokers with
      expected comparable results. There was a medication effect that was independent
      of any predictor except older age and those who gained no or minimal weight
      during the open-label phase. Predictors of successful relapse prevention included
      lower baseline smoking rates, a Fagerstrom Tolerance Questionnaire score of < 6,
      and initiation of smoking at an older age. These data should encourage others to
      perform similar pharmacologic relapse prevention studies with this or other
      pharmacotherapies.

PMID- 12188589
TI  - Intraclass correlation among measures related to cigarette use by adolescents:
      estimates from an urban and largely African American cohort.
AB  - This paper presents the first estimates of school-level intraclass correlation
      (ICC) for smoking-related variables from an urban and largely African American
      population. Seventh graders (n = 6967) from 39 middle schools in Memphis, TN,
      were measured at baseline in 1994 and annually through 1997. Mixed model
      regression methods were used to estimate variance components for school and
      residual error. School-level ICCs were large enough, if ignored, to substantially
      inflate the Type I error rate in an analysis of treatment effects. We show how
      those correlations can be reduced using regression adjustments and used to
      determine sample size for future school-based smoking prevention studies.

PMID- 12188590
TI  - The effects of alcohol and anxiousness on physiological and subjective responses
      to a social stressor in women.
AB  - Several studies have examined the validity of the tension reduction hypothesis as
      an explanatory model for the development of alcohol problems, but support has
      been inconsistent. In recent years, researchers have begun to examine how various
      individual differences variables moderate the relationship between alcohol
      consumption and reduction of anxiety. The present study examined how 40 women,
      either moderate or low in anxiety sensitivity (AS), responded to a social
      stressor (giving a body image speech) after consuming either a low dose of
      alcohol (0.4 ml/kg of body weight) or a placebo. Results indicated that of the
      participants reporting moderate AS, participants consuming alcohol reported more
      stress dampening as measured by heart rate in anticipation to the stressor than
      participants not consuming alcohol. Furthermore, of the participants consuming
      alcohol, those reporting high social anxiety reported more of an increase in
      heart rate than participants not consuming alcohol. Findings are discussed in
      terms of considering individual differences factors when examining predictions
      made from the tension reduction hypothesis.

PMID- 12188591
TI  - The addition of social support to a community-based large-group behavioral
      smoking cessation intervention: improved cessation rates and gender differences.
AB  - OBJECTIVE: To determine the effects on cessation rates of adding a partner
      support group component to a large-group community-based behavioral smoking
      cessation program. METHODS: During the past eight smoking cessation programs at
      the Tom Baker Cancer Centre in Calgary, Alberta, Canada, separate support group
      sessions were offered for support persons of prospective quitters. Six hundred
      smokers brought 156 support people with them to the groups. Cessation rates were
      calculated at 3, 6, and 12 months postquit. RESULTS: Those smokers who had
      support people attending at least one of the support group sessions had higher
      cessation rates at 3, 6, and 12 months (56%, 46%, and 43%) compared to those
      without a support person in attendance (36%, 35%, 32%). This effect was
      especially strong for men, with 3-, 6-, and 12-month cessation rates for those
      with support of 58%, 54%, and 56%, compared to 52%, 41%, and 36% in the women
      with support. For men without a support person, the rates were 34%, 35%, and 33%,
      compared to 38%, 35%, and 31% in women without support. This indicates that
      although support was initially effective for women, it had no effect on sustained
      abstinence. CONCLUSIONS: The addition of a support person group to a large-group
      behavioral smoking cessation program was effective in improving 3-month cessation
      rates in both men and women, but over 1-year of follow-up support was only
      associated with greater sustained abstinence in men.

PMID- 12188592
TI  - Age of onset and body dissatisfaction in obesity.
AB  - This study investigated variation in body dissatisfaction among obese women in
      relation to age of onset of obesity, and evaluated the contribution of teasing
      about weight and self-esteem as possible causes of higher body dissatisfaction in
      the early-onset group. One hundred and five obese women (body mass index [BMI] >
      or =30), recruited from clinical settings in England, completed a mailed
      questionnaire. The early-onset group (by age 16) had a higher BMI, greater body
      dissatisfaction, and lower self-esteem. Predictably, they also reported more
      childhood teasing. Path analyses confirmed our expectation that early onset of
      obesity has an adverse effect on body image, which is independent of current BMI.
      Regression analyses failed to support the hypothesized mediating role of either
      childhood teasing or lower self-esteem. The possible direction of causal effects
      between body dissatisfaction and self-esteem is discussed, with the suggestion
      that early onset of obesity increases the risk of body dissatisfaction, which in
      turn impairs self-esteem.

PMID- 12188593
TI  - Self-detoxification attempts among methadone maintenance patients: what methods
      and what success?
AB  - In a study of patients attending a methadone maintenance clinic in South London,
      66 of 114 (58%) had previously attempted to detoxify themselves from opiates
      without medical assistance. The total number of self-detoxification attempts was
      237, an average of 3.6 attempts per individual. Forty subjects (61%) reported
      attempting self-detoxification with the help of drugs or alcohol. The drugs most
      commonly used were diazepam, alcohol, and cannabis. The most commonly reported
      reasons for attempting self-detoxification were "fed-up with the lifestyle" (61%)
      and "for their family" (12%). The reasons given for why patients had decided to
      detoxify themselves rather than access treatment services included 23% who
      reported that "they could cope on their own and that they didn't need any help."
      The short-term success rate (abstinent for at least 24 hours) was moderate, at
      41% (97/237). Patients who had been unsuccessful were asked why their last self
      detoxification attempt had not resulted in abstinence, with 27% reporting that
      they were "tempted to use again" and 23% reported that they "didn't know why they
      started using again." The prevalence of both attempts and success suggests that,
      for some opiate users, self-detoxification may be a pathway to abstinence.

PMID- 12188594
TI  - Matching substance abuse aftercare treatments to client characteristics.
AB  - This study investigated matching client attributes to different aftercare
      treatments. A naturalistic sample of adults entering substance abuse treatment
      was randomized into either Structured Relapse Prevention (RP, n=61) or a 12-Step
      Facilitation (TSF, n=72) aftercare program. Four patient attributes were matched
      to treatment: age, gender, substance abuse profile, and psychological status.
      Substance use outcomes were assessed 3 and 6 months posttreatment. At 6 months,
      four significant matches were uncovered. Females and individuals with a multiple
      substance abuse profile reported better alcohol outcomes with TSF aftercare than
      their cohorts exposed to RP aftercare. Individuals with high psychological
      distress at treatment entry were able to maintain longer periods of posttreatment
      abstinence with TSF aftercare compared to their cohorts exposed to RP. Inversely,
      RP was found to maintain abstinence significantly longer for individuals
      reporting low distress compared to those with high distress. Finally, better
      outcomes were achieved when random assignment to aftercare was consistent with
      participant preference. Overall, an Alcoholics Anonymous approach to aftercare
      appears to provide the most favorable substance use outcomes for most groups of
      substance abusers. RP may be most suitable for clients whose psychological
      distress is low, especially where maintenance of abstinence is targeted. Where
      choice in aftercare program is possible, matching client preference with type of
      aftercare program can improve outcome.

PMID- 12188595
TI  - Testing stage effects in an ethnically diverse sample.
AB  - The Transtheoretical Model (TTM) has been extensively validated in representative
      samples of adult smokers. Stage effects, i.e., the patterned relationships
      between Stage of Change (SOC) and other TTM variables, have been reported in a
      variety of samples. This study describes reliability data for the TTM variables
      and tests the stage effects with an ethnically diverse sample of 296 parents with
      young children. On the basis of theory and previous empirical evidence from a
      general population, it is possible to make quantitative predications about the
      magnitude of the expected effect sizes for the Decisional Balance, Situational
      Temptations, and Processes of Change subscales. For each variable, both a test of
      significance and a comparison with the expected effect sizes is reported. Results
      indicated significant stage differences for 8 of the 11 TTM subscales, and all
      quantitative predictions were confirmed. This study supports the use of TTM
      measures in an ethnically diverse sample.

PMID- 12188596
TI  - Evaluating the Lions-Quest "Skills for Adolescence" drug education program: first
      year behavior outcomes.
AB  - Thirty-four schools (n=7426 consented sixth graders, 71% of the eligible
      population) were randomized to conditions to test the hypothesis that "Skills for
      Adolescence" (SFA) is more effective than standard care in deterring and delaying
      substance use through middle school. One-year posttest data were collected from
      6239 seventh graders (84% of those eligible). Initiation of "ever" and "recent"
      use of five substances for baseline nonusers and changes in recent use for
      baseline users by experimental condition were compared using mixed model
      regression to control for school clustering. For pretest nonusers, recent
      cigarette smoking was lower for SFA than controls (P<.05), as was lifetime
      marijuana use (P<.06). There were also three Treatment x Ethnicity interactions
      around drinking behaviors. Hispanics in SFA were less likely to ever and recently
      drink, and to recently binge drink than Hispanic controls; there were no
      treatment differences among non-Hispanics. For baseline users, there were three
      significant SFA delays in transition to experimental or recent use of more
      "advanced" substances: drinking to smoking, drinking to marijuana use, and binge
      drinking to marijuana.

PMID- 12188597
TI  - Conflict resolution style as an indicator of adolescents' substance use and other
      problem behaviors.
AB  - Reports of violence in schools across the nation prompted us to investigate how
      adolescents resolve conflicts among themselves. We hypothesized that adolescents
      who act out at school ("problem students") do so because they have acquired
      maladaptive conflict resolution styles compared to students who do not manifest
      conduct problems at school ("nonproblem students"). We further hypothesized that
      inappropriate conflict resolution skills would be associated with a variety of
      other maladaptive behaviors. Sixty-one adolescents from a public high school (31
      problem and 30 nonproblem students) participated in this study. Based on the dual
      concern model of conflict resolution, four interpersonal conflict resolution
      styles were assessed via self-report and videotaped behavioral enactment:
      cooperation, contentiousness, accommodation, and avoidance. Findings indicated
      that the problem adolescents were less cooperative and more contentious in
      conflict situations with peers. Maladaptive conflict resolution styles were
      associated with a range of externalizing behaviors including fighting, cigarette
      smoking, drinking, and marijuana use as well as low academic achievement. This
      study supports a role for conflict resolution style in studies of adolescent
      problem behavior and makes recommendations for the design of school-based
      prevention programs.

PMID- 12188598
TI  - Depression and smoking during pregnancy.
AB  - This study examined the relationship between depression and smoking during a
      woman's pregnancy. It surveyed 487 pregnant women (aged 17-44) during routine
      ultrasound examinations at the 18th week of gestation. A multiple regression
      analysis showed that depression is a significant predictor of smoking during
      pregnancy, after controlling for other factors such as the desirability of the
      pregnancy and the presence of other smokers in the household. Both current
      smokers and former smokers were significantly more likely to report depressive
      symptoms (using Centers for Epidemiological Studies Depression Scale, CES-D) than
      never smokers; the rates are 12.9%, 25.1%, and 37.5% for never, former, and
      current smokers, respectively. Among current smokers, the depressed were
      significantly less confident about quitting than the nondepressed, although both
      felt the need to quit. These results suggest that interventions to help pregnant
      women quit smoking may need to take a more comprehensive approach to be
      effective.

PMID- 12188599
TI  - Comparison of peroxide value methods used for semihard cheeses.
AB  - The objective was to evaluate alternatives to the peroxide value method of choice
      in the dairy industry, the method issued by the International Dairy Federation.
      Furthermore, the study evaluated the feasibility of alternative solvents for
      extracting lipids and subsequent peroxide value determinations. Packaged cheeses
      were stored under illuminated display at 4 degrees C to obtain samples with
      various peroxide contents but with uniform gross composition. The hydroperoxide
      contents were measured during 3 weeks of storage by applying two lipid extraction
      methods, Folch and Bureau of Dairy Industry (BDI) extractions, and three
      different hydroperoxide extraction solutions [chloroform/methanol (7:3, v/v),
      hexane/2-propanol/methanol (5:7:2, v/v/v), and methanol/decanol/hexane (3:2:1,
      v/v/v)], prior to standard colorimetric measurements. Extraction yields of fat
      from Havarti cheeses using the Folch and BDI extraction methods were
      approximately 109 and 61%, respectively, of the yields obtained by the
      International Dairy Federation gravimetric reference method. Although differences
      in fat extraction yields were compensated for, significantly higher peroxide
      values resulted from the Folch extraction method than from the BDI extraction
      method. The peroxide values obtained by the three methods were all in the same
      range, and pronounced linear correlations between peroxide contents determined
      using the three solutions were noted (r (2) in the range of 0.951-0.983).
      Peroxide value levels were not significantly different in samples stored in the
      dark or exposed to light.

PMID- 12188600
TI  - High-performance liquid chromatographic determination of biogenic amines in
      poultry carcasses.
AB  - Biogenic amines, produced by bacterial decarboxylation of amino acids, have been
      associated with toxicological symptoms in broilers fed various poultry
      byproducts. A reversed-phase high-performance liquid chromatographic method is
      described for the quantitation of eight biogenic amines (tryptamine,
      phenylethylamine, putrescine, cadaverine, histamine, tyramine, spermidine, and
      spermine) in chicken carcasses. Amines were extracted with perchloric acid,
      derivatized with dansyl chloride, separated using gradient elution (methanol and
      water), and detected by fluorescence. Benzylamine was used as the internal
      standard. Linearity, repeatability, and recovery of the method were evaluated.
      The method was linear for all of the amines studied at concentrations ranging
      from 0.05 to 25 microg/mL. Average recoveries ranged from 92.6% to 96.8% for all
      amines except for histamine, which was 74.6%.

PMID- 12188601
TI  - Characterization of commercial kava-kava herbal drug and herbal drug preparations
      by means of nuclear magnetic resonance spectroscopy.
AB  - The efficiency of one- and two-dimensional NMR experiments in characterizing the
      content of the constituents of both herbal drugs and herbal drug preparations is
      demonstrated for kava-kava. These experiments directly detect active constituents
      represented by kavalactones in both a finely powdered herbal drug and a
      commercial extract. In addition, NMR spectroscopy can detect all other compounds
      present in the extract. As previously evidenced, NMR experiments can represent a
      generally applicable technique for rapid screening and are a complement to the
      classical analytical techniques such as high-performance thin-layer
      chromatography, high-performance liquid chromatography, capillary gas
      chromatography, and electrophoresis. These experiments can be considered a very
      simple and fast analytical method to obtain a fingerprint of the herbal drugs and
      their preparations, and to quantify the content of the active principles of the
      extract.

PMID- 12188602
TI  - Determination of triazine and chloroacetanilide herbicides in soils by microwave
      assisted extraction (MAE) coupled to gas chromatographic analysis with either GC
      NPD or GC-MS.
AB  - A simple and rapid method based on microwave-assisted extraction (MAE) coupled to
      gas chromatographic analysis was developed for the analysis of triazine
      (atrazine, cyanazine, metribuzine, simazine and deethylatrazine, and
      deisopropylatrazine) and chloroacetanilide (acetochlor, alachlor, and
      metolachlor) herbicide residues in soils. Soil samples are processed by MAE for 5
      min at 80 degrees C in the presence of acetonitrile (20 mL/sample). Mean recovery
      values of most solutes are >80% in the 10 to 500 microg/kg fortification range
      with respective RSDs (relative standard deviations) < 20%. The limits of
      quantification (LOQ) and limits of detection (LOD) are 10 and 1 to 5 microg/kg,
      respectively. The method was validated with two types of soils containing 1.5 and
      3.0% organic matter content, respectively; no statistically significant
      differences were found between solute recovery values from the two types of
      soils. The solute mean recovery values from freshly spiked (24 h aging) and
      spiked samples stored refrigerated for one week before processed were also not
      statistically different. Residue levels determined in field weathered soils were
      higher when soils were processed by MAE than with a comparison method based on
      flask-shaking of soil suspensions overnight. Extracts were analyzed by a gas
      chromatographic system equipped either with a thermionic (GC-NPD) or a mass
      spectrometric detector (GC-MS).

PMID- 12188603
TI  - Antioxidant activity of black currant anthocyanin aglycons and their glycosides
      measured by chemiluminescence in a neutral pH region and in human plasma.
AB  - The antioxidant activity of nine anthocyanin glycosides was measured in a neutral
      pH region using a chemiluminescence (CL) emission system in the presence of an
      H(2)O(2)-acetaldehyde system, and the intensities were found to be affected by
      three factors, pH value and both moieties of the aglycon and C-3 sugar. With an
      increase in pH from 4.0 to 9.0, the CL intensities increased from pH 5.0, reached
      their maxima at pH 6.0-7.0, and decreased at pH 9.0. Comparison of the
      intensities among the 3-glucosides with five different aglycons and the 3
      glycosides with three different sugar moieties at C-3 showed that their strongest
      intensities were given by the delphinidin aglycon and 3-rutinosyl moiety,
      respectively. Monitoring of the CL intensity of human blood plasma for 8 h after
      oral administration of black currant anthocyanins (BCA) showed a rapid increase
      until 2 h, and a significant difference (P < 0.05) was recognized at 1-8 h.

PMID- 12188605
TI  - Antioxidant activities of phenolic, proanthocyanidin, and flavonoid components in
      extracts of Cassia fistula.
AB  - Cassia fistula L., a semi-wild Indian Labernum, is widely cultivated in Mauritius
      as an ornamental tree for its beautiful bunches of yellow flowers and also used
      in traditional medicine for several indications. The total phenolic,
      proanthocyanidin, and flavonoid contents, and the antioxidant activities, of
      fresh vegetative and reproductive organs of Cassia fistula harvested at different
      stages of growth were determined using the Trolox equivalent antioxidant capacity
      (TEAC) and ferric-reducing antioxidant power (FRAP) assays. The antioxidant
      activities were strongly correlated with total phenols (TEAC r = 0.989; FRAP r =
      0.951) in all organs studied, and with proanthocyanidins (TEAC r = 0.980; FRAP r
      = 0.899) in reproductive organs including fruits. The antioxidant activities of
      reproductive parts were higher than those of the vegetative organs, with the pods
      having highest total phenolic, proanthocyanidin, and flavonoid contents and
      antioxidant potentials (TEAC = 992 +/- 0.4 micromol/g dry weight; FRAP = 811 +/-
      23 micromol/g dry weight).

PMID- 12188606
TI  - Insect antifeedants from tropical plants II: structure of zumsin.
AB  - A novel A-seco limonoid was isolated from methanolic extract of Croton
      jatrophoides and designated as zumsin. This compound showed potent antifeedant
      activity against two lepidopteran larvae, pink bollworm, Pectinophora gossypiella
      (PC(50) = 1 microg/cm(2), PC(95) = 8 microg/cm(2)), and fall armyworm, Spodoptera
      frugiperda (PC(50) = 2 microg/cm(2), PC(95) = 16 microg/cm(2)). The structure of
      zumsin was determined as 1 using a variety of spectroscopic methods including
      nuclear magnetic resonance, mass spectrometry, and circular dichroism. The
      structure consists of an A'-B trans-fused ring while dumsin (2), a constituent of
      the same source, maintains an A'-B cis-fused ring, and suggests two unique
      biosynthetic processes after A ring oxidative expansion.

PMID- 12188604
TI  - Spectrophotometric determination of substrate-borne polyacrylamide.
AB  - Polyacrylamides (PAMs) have wide application in many industries and in
      agriculture. Scientific research and industrial applications manifested a need
      for a method that can quantify substrate-borne PAM. The N-bromination method (a
      PAM analytical technique based on N-bromination of amide groups and
      spectrophotometric determination of the formed starch-triiodide complex), which
      was originally developed for determining PAM in aqueous solutions, was modified
      to quantify substrate-borne PAM. In the modified method, the quantity of
      substrate-borne PAM was converted to a concentration of starch-triiodide complex
      in aqueous solution that was then measured by spectrophotometry. The method
      sensitivity varied with substrates due to sorption of reagents and reaction
      intermediates on the substrates. Therefore, separate calibration for each
      substrate was required. Results from PAM samples in sand, cellulose, organic
      matter burnt soils, and clay minerals showed that this method had good accuracy
      and reproducibility. The PAM recoveries ranged from 95.8% to 103.7%, and the
      relative standard deviations (n = 4) were <7.5% in all cases. The optimum range
      of PAM in each sample is 10-80 microg. The technique can serve as an effective
      tool in improving PAM application and facilitating PAM-related research.

PMID- 12188607
TI  - Antioxidant capacity of different broccoli (Brassica oleracea) genotypes using
      the oxygen radical absorbance capacity (ORAC) assay.
AB  - Antioxidant capacity of hydrophilic and lipophilic extracts from eight broccoli
      genotypes was compared using the oxygen radical absorbance capacity (ORAC) assay.
      Each genotype was analyzed for carotenoid, tocopherol, ascorbic acid, and
      flavonoid content. Results indicate that the antioxidant capacity of hydrophilic
      extracts ranged from 65.8 to 121.6 micromol trolox equivalents (TE)/g of tissue,
      and the capacity of lipophilic extracts ranged from 3.9 to 17.5 micromol TE/g.
      Ascorbic acid and flavonoid content of the hydrophilic extracts did not explain
      the total variation in antioxidant capacity of those extracts, suggesting either
      the presence of other antioxidant components that have yet to be identified or
      that the known antioxidants are producing synergistic effects. The carotenoids
      did correlate with antioxidant capacity of the lipophilic extracts and accounted
      for the majority of the variability in that fraction. The variability in
      hydrophilic and lipophilic antioxidant capacity found among these genotypes
      suggests that potential efficacy from antioxidants will vary considerably from
      genotype to genotype.

PMID- 12188608
TI  - Chicken model for studying dietary antioxidants reveals that apple (Cox's
      Orange)/broccoli (Brassica oleracea L. var. italica) stabilizes erythrocytes and
      reduces oxidation of insoluble muscle proteins and lipids in cooked liver.
AB  - A chicken model for studying the effects of antioxidants in the diet on oxidative
      status was set up. Chickens fed a semi-synthetic diet low in antioxidants showed
      a remarkable decrease in erythrocyte stability toward H(2)O(2) or 2,2'-azobis (2
      amidinopropane) dihydrochloride (AAPH), but increases in catalase activity in
      liver, carbonyls in insoluble muscle proteins, and enhanced lipid oxidation in
      heat-treated liver samples compared to that of conventionally fed chickens. Thus,
      this chicken model proved to be more susceptible to oxidative changes than
      conventionally fed chickens, reflecting a low antioxidative defense.
      Supplementing this low antioxidant diet with 10% apple/broccoli mixture
      counteracted these changes, except for activity of catalase in the liver and AAPH
      induced lysis of erythrocytes. Supplementation with 10% sweet corn only reduced
      the carbonyl content in insoluble proteins. However, neither low antioxidant diet
      nor vegetable supplements affected selected antioxidative enzymes or oxidative
      stability of lipids in heat-treated muscle tissue.

PMID- 12188609
TI  - Characterization and identification of alfalfa and red clover dietary supplements
      using a PCR-based method.
AB  - The use of herbal remedies is very popular in the United States, with >80 million
      people buying plant-derived preparations that are often highly degraded or
      potentially contaminated with nonefficacious plant material. A method utilizing
      DNA-based markers to identify highly fragmented or powdered plant material sold
      as botanicals in dietary supplements has been developed. By incorporating and
      streamlining a repair reaction that utilized fill-in and ligation reactions
      before the PCR steps, it was possible to amplify highly degraded or sheared DNA
      isolated from powdered plant material removed from over-the-counter capsules. The
      primers for the internal transcribed spacer (ITS) region of nuclear ribosomal DNA
      generate a PCR fragment compatible with the sizes of the repaired DNA. Moreover,
      a large data set in Genbank facilitated subsequent analysis. This method is a
      relatively rapid and simple system to facilitate the authentication, as well as
      the monitoring, of the purity of botanicals in dietary supplements, even those
      that are improperly dried or stored.

PMID- 12188610
TI  - Temperature and pH effects on biodegradation of hexachlorocyclohexane isomers in
      water and a soil slurry.
AB  - This study was conducted to monitor the biodegradation of alpha-, beta-, gamma-,
      and delta-hexachlorocyclohexane (HCH) isomers in liquid culture by a Pandoraea
      species and determine the influence of pH and temperature on the biodegradation
      of alpha- and gamma-HCH in liquid as well as in soil slurry cultures. The
      Pandoraea species degraded 79.4% delta-HCH and 34.3% gamma-HCH in liquid culture
      at 4 weeks of incubation. alpha- and beta-HCH exhibited almost identical rates
      (41.6 and 42.4%, respectively) of degradation. The highest degradation of alpha-
      and gamma-HCH (67.1 and 60.2%, respectively) was observed at an initial pH of 8.0
      in liquid; 58.4 and 51.7% rates of degradation of alpha- and gamma-HCH,
      respectively, at an initial pH of 9.0 were found in soil slurry cultures. An
      incubation temperature of 30 degrees C was optimum for effective degradation of
      alpha- and gamma-HCH isomers (62.5 and 57.7%, respectively) in liquid culture,
      and 54.3 and 51.9% rates of degradation of alpha- and gamma-HCH isomers,
      respectively, were found in a soil slurry. Increasing the soil/water ratio
      decreased the extent of degradation of both HCH isomers. Degradation of HCH
      isomers occurred concomitant with bacterial growth. Byproducts of growth from
      Pandoraea species significantly decreased the pH of the liquid and the soil
      slurry during the growth on HCH isomers. The results of this study suggest that
      this bacterial strain may effectively be used for remediating polluted sites and
      water contaminated with different HCH isomers over a range of environmental
      conditions.

PMID- 12188611
TI  - Molecular species of acylglycerols incorporating radiolabeled fatty acids from
      castor (Ricinus communis L.) microsomal incubations.
AB  - Sixty-one molecular species of triacylglycerols (TAG) and diacylglycerols
      produced from castor microsomal incubations incorporating six different (14)C
      labeled fatty acids have been identified and quantified. The preference for
      incorporation into TAG was in the order ricinoleate > oleate > linoleate >
      linolenate > stearate > palmitate. Ricinoleate was the major fatty acid
      incorporated, whereas stearate, linolenate, and palmitate were incorporated at
      low levels. Twenty-one molecular species of acylglycerols (HPLC peaks) in castor
      oil have also been assigned. The levels of TAG in castor oil are RRR
      (triricinolein) >> RR-TAG >> R-TAG > no R-TAG. The levels of the molecular
      species within the groups of RR-TAG, RL-TAG, and LL-TAG individually are
      ricinoleate > linoleate > oleate > linolenate, stearate, and palmitate. The
      results of the labeled fatty acid incorporation are consistent with ricinoleate
      being preferentially driven into TAG and oleate being converted to ricinoleate in
      castor oil biosynthesis.

PMID- 12188612
TI  - Texture of cooked potatoes (Solanum tuberosum). 1. Relationships between dry
      matter content, sensory-perceived texture, and near-infrared spectroscopy.
AB  - Properties of fresh potatoes, including dry matter (DM) content, starch content,
      and near-infrared (NIR) spectra, were determined and related to the sensory
      perceived texture of the steam-cooked samples. To quantify these relationships,
      three potato cultivars, respectively representing a firm cooking potato (cv.
      Nicola), a mealy cooking potato (cv. Irene), and a cultivar (cv. Bintje) with
      intermediate cooking properties, were classified on the basis of three size
      categories. For each size category and cultivar a DM distribution was determined
      on the basis of the underwater weight of the individual potatoes. Each DM
      distribution was divided into three subcategories based on low, medium, and high
      DM contents. This categorization was performed for freshly harvested potatoes and
      for potatoes stored for 3 and 6 months, respectively. In total, this resulted in
      27 DM distributions, of which 16 were non-normally distributed, and 81 samples.
      Linear relationships were established between the DM content, as determined by
      either underwater weight analysis or oven-drying, and the starch content. On the
      basis of partial least-squares regression (PLSR), statistical models were
      developed relating sensory-based texture descriptors with the DM matter content
      of the samples. It was also shown, by applying PLSR, that the NIR spectra,
      originating from the potato samples, could be related to the DM content and to
      the sensory-perceived texture. From the relationships between DM content and
      sensory-perceived texture, on the one hand, and from the DM content and NIR
      spectra, on the other, it was concluded that the DM content rather than the
      cultivar determines the sensory-perceived texture of steam-cooked potatoes.
      Cultivar-specific elements may also contribute to the perceived texture but are
      overruled by the DM content. Storage did not affect the mutual relationships
      between the DM content, the sensory properties, and the NIR spectra.

PMID- 12188614
TI  - Texture of cooked potatoes (Solanum tuberosum). 3. Preheating and the
      consequences for the texture and cell wall chemistry.
AB  - Two potato cultivars representing extremes with regard to the texture of the
      cooked product were divided into subcategories based on size and dry matter (DM)
      content. The effects of the preheating temperature and time on both the
      instrumentally determined firmness and the sensory-perceived firmness were
      measured and compared. Increasing the preheating time at 60 degrees C followed by
      cooking resulted in greater force required to fracture the tissue, an increase in
      perceived firmness, and a less mashable product. A principal component analysis
      showed that with higher DM contents of the potato samples, preheating resulted in
      a larger force required to fracture the tissue and a firmer product. The changes
      in fracture force were not linearly related with the changes in perceived
      firmness. The effects of preheating on the pectin methylesterase (PME) activity,
      the enzyme assumed to be responsible for the firming effect upon preheating,
      showed that the activity of this enzyme remained rather constant during
      preheating at 60 degrees C for 1 h. Preheating at 78 degrees C for 10 min
      abolished virtually all PME activity. To obtain insight into the consequences of
      preheating and preheating followed by steam cooking on the yield and composition
      of the cell wall material (CWM) of potatoes, a cell wall isolation followed by a
      pectin fractionation study was performed. Attention was also paid to the
      consequences of the processing conditions applied on the chemical composition of
      the CWM and the sequentially extracted pectic fractions. Preheating resulted in
      an increase in yield of the CWM of cooked potatoes and, as a consequence, all of
      the sequentially extracted fractions, including the residue. Preheating did not
      have a pronounced effect on the composition of the pectin of the sequentially
      extracted fractions. This altogether strongly indicates that preheating causes a
      PME-based firming effect, resulting in an decrease in pectin degradation and, as
      a consequence, a larger yield of CWM. It seems reasonable to assume that this
      increase in amount of CWM results in a firmer texture. The contribution of starch
      based degradation products to the texture after preheating can, however, not be
      excluded.

PMID- 12188613
TI  - Texture of cooked potatoes (Solanum tuberosum). 2. Changes in pectin composition
      during storage of potatoes.
AB  - During the storage season changes in the chemical composition of the pectin
      moiety of the cell walls of raw potatoes were studied. This compositional
      analysis was performed for the cultivars Nicola and Irene, which represent two
      extremes with regard to sensory-perceived texture. Both cultivars were divided
      into three size categories. From each size category a dry matter (DM)
      distribution was made. From these distributions potatoes at the low and high ends
      of this distribution were selected for further analysis. In total 12 different
      samples were analyzed three times during the storage season. The analysis
      comprised a pectin fractionation study. Pectic fractions were extracted from the
      cell wall material (CWM) by increasing the harshness of the extraction procedure.
      This resulted in a calcium-complexed pectic fraction, two pectic fractions weakly
      bound to the CWM, and a residue fraction, respectively. It was shown that no
      statistically significant differences (p > or = 0.95), either in yield or in
      chemical composition, could be observed between the two cultivars studied (Nicola
      and Irene), between sizes (large, medium, and small), and between potatoes with
      either high or low DM contents. However, statistically significant effects of
      storage both on the yield and on the chemical composition of the pectic moiety of
      the CWM could be observed, irrespective of cultivar, size, and DM content.
      Despite the substantial changes in the composition of the pectic moiety of the
      CWM of the raw material, no to minimal changes in the sensory-perceived texture
      of the cooked potatoes were observed upon storage. This suggests that the
      observed changes in pectin composition upon storage are overruled by other
      aspects that contribute more importantly to the sensory-perceived texture of
      steam-cooked potatoes.

PMID- 12188615
TI  - Effect of processing techniques at industrial scale on orange juice antioxidant
      and beneficial health compounds.
AB  - Phenolic compounds, vitamin C (L-ascorbic acid and L-dehydroascorbic acid), and
      antioxidant capacity were evaluated in orange juices manufactured by different
      techniques. Five processes at industrial scale (squeezing, mild pasteurization,
      standard pasteurization, concentration, and freezing) used in commercial orange
      juice manufacturing were studied. In addition, domestic squeezing (a hand
      processing technique) was compared with commercial squeezing (an industrial FMC
      single-strength extraction) to evaluate their influences on health components of
      orange juice. Whole orange juice was divided into soluble and cloud fractions
      after centrifugation. Total and individual phenolics were analyzed in both
      fractions by HPLC. Commercial squeezing extracted 22% more phenolics than hand
      squeezing. The freezing process caused a dramatic decrease in phenolics, whereas
      the concentration process caused a mild precipitation of these compounds to the
      juice cloud. In pulp, pasteurization led to degradation of several phenolic
      compounds, that is, caffeic acid derivatives, vicenin 2 (apigenin 6,8-di-C
      glucoside), and narirutin (5,7,4'-trihydroxyflavanone-7-rutinoside) with losses
      of 34.5, 30.7, and 28%, respectively. Regarding vitamin C, orange juice produced
      by commercial squeezing contained 25% more of this compound than domestic
      squeezing. Mild and standard pasteurization slightly increased the total vitamin
      C content as the contribution from the orange solids parts, whereas concentration
      and freezing did not show significant changes. The content of L-ascorbic acid
      provided 77-96% of the total antioxidant capacity of orange juice. Mild
      pasteurization, standard pasteurization, concentration, and freezing did not
      affect the total antioxidant capacity of juice, but they did, however, in pulp,
      where it was reduced by 47%.

PMID- 12188616
TI  - Degradation pathway of dicyclanil in water in the presence of titanium dioxide.
      Comparison with photolysis.
AB  - The solar photolytic behavior of the pesticide 4,6-diamino-2-cyclopropyl
      pyrimidine-5-carbonitrile, currently known as dicyclanil, has been mimicked in a
      photoreactor operating with an artificial light flux. The rate and pathway of
      degradation were performed. An additional study, using TiO(2) photocatalysis, has
      been achieved in order to determine the efficiency of photocatalysis to degrade
      the molecule. The catalyst was titania Degussa P-25. The aim of this article was
      the identification of the intermediate products formed during the irradiation, to
      establish the degradation pathway of dicyclanil. The kinetics of the reactions
      were followed by liquid chromatography with a diode array detector (LC-DAD). Most
      of the organic compounds occurring during the photodegradation have been
      identified by means of liquid chromatography and mass spectrometry coupled
      techniques (HPLC-MS). Additional analyses were carried out to evaluate the
      mineralization rates into nitrate and ammonium ions.

PMID- 12188617
TI  - Xylanase, beta-glucanase, and other side enzymatic activities have greater
      effects on the viscosity of several feedstuffs than xylanase and beta-glucanase
      used alone or in combination.
AB  - This study was carried out to evaluate the effects of a pure xylanase, a pure
      beta-glucanase, a mix of the two pure enzymes, and a commercial enzyme
      preparation (Quatrazyme HP, Nutri-Tomen Les Ulis, France) on the viscosity
      exhibited by water-soluble nonstarch polysaccharides of several feedstuffs
      (Rialto wheat, Sideral wheat, Isengrain wheat, triticale, rye, barley, oats,
      corn, wheat bran, rice bran, wheat screenings, soybean meal, rapeseed meal,
      sunflower meal, and peas). The viscosity depended on the feedstuffs and varieties
      of the same feedstuff. There was a correlation (R (2) = 0.86) between viscosity
      of cereals and their arabinoxylan and beta-glucan contents. The correlation was
      greater (R (2) = 0.99) when the type of cereal was taken into account. The
      addition of pure xylanase significantly decreased the viscosity of all feedstuffs
      except sunflower meal (P < or = 0.05). However, pure beta-glucanase was unable
      significantly to decrease the viscosity of Isengrain wheat, corn, rice bran,
      wheat screenings, soybean meal, and sunflower meal. There was a greater decrease
      in viscosity with the combination of xylanase and beta-glucanase than with
      addition of xylanase or beta-glucanase alone. This synergistic action of xylanase
      and beta-glucanase was observed only in Rialto wheat, Sideral wheat, triticale,
      rye, barley, oats, and peas. Finally, the commercial enzyme preparation produced
      a greater reduction (P < or = 0.05) in viscosity for all feedstuffs compared to
      xylanase or beta-glucanase used alone or in combination. The greater
      effectiveness of the commercial enzyme preparation was due to the presence of
      side enzymatic activities (arabinofuranosidase, xylosidase, glucosidase,
      galactosidase, cellulase, and polygalacturonase).

PMID- 12188618
TI  - Determination of selenium concentration of rice in china and effect of
      fertilization of selenite and selenate on selenium content of rice.
AB  - A method of hydride generation atomic fluorescence spectrometry was applied to
      the determination of the selenium concentration of regular polished rice in China
      and selenium-enriched polished rice obtained by foliar application of selenium
      enriched fertilizer in the forms of selenite and selenate. The average selenium
      content of regular rice was 0.025 +/- 0.011 microg g(-)(1). On the basis of a
      daily dietary rice intake of 300-500 g suggested by the China Nutrition Society,
      the total selenium intake from regular rice was calculated to be 7.5-12.5 microg
      per person per day for an adult. The selenium contents of rice were significantly
      increased to 0.471-0.640 microg g(-)(1) by foliar application of selenium
      enriched fertilizer at rate of 20 g of Se ha(-)(1) in the forms of sodium
      selenite and sodium selenate. The selenium content of rice by application of a
      fertilizer of selenate was 35.9% higher than that by a fertilizer of selenite,
      which showed that Se-enriched fertilizer in selenate exhibited greater efficiency
      in increasing Se content in rice products. The Se-enriched rice products can
      increase daily Se intake on average by 100-200 microg of Se per day by the
      consumption of 400 g of rice products if the Se level of rice products is
      controlled at 0.3-0.5 microg of Se g(-)(1). Because rice is a staple food in
      China, selenium-enriched rice obtained by bioenrichment of selenium to increase
      the Se content of rice could be a good selenium source for the population in
      selenium-deficient regions.

PMID- 12188620
TI  - The application of thermal desorption GC/MS with simultaneous olfactory
      evaluation for the characterization and quantification of odor compounds from a
      dairy.
AB  - Few analytical methods exist that combine chemical and sensory analysis of
      odorous compounds in whole air. Volatile organic compounds were collected by
      sampling air downwind from a small dairy through sorbent tubes of Tenax TA and
      Carboxen 569. Samples were analyzed by thermal desorption into a cryotrap and
      subsequent gas chromatographic separation, followed by simultaneous olfactometry
      and mass spectrometry. Because compounds are concentrated during sampling,
      sensory analysis encountered compounds at a concentration 40 times that in air,
      making this a useful method for identifying trace compounds participating in
      odor. Twenty odorous and nonodorous compounds were identified and quantified,
      including straight-chain and aromatic hydrocarbons, chlorinated compounds,
      alcohols, ketones, aldehydes, and organic acids, at air concentrations of 0.55
      320.20 microg/m(3). Compound peaks were characterized by odors ranging from
      offensive to pleasant, demonstrating the integrative nature of olfaction. This
      method could be useful in studying many kinds of odors in air.

PMID- 12188619
TI  - Diterpenoids from Cascarilla (Croton eluteria Bennet).
AB  - Cascarilla is a commercially available and cheap source of polyfunctionalized
      diterpenoids belonging to the clerodane structural type. In addition to the
      bitter triol cascarillin, 10 additional new diterpenoids (eluterins A-J) have
      been isolated and characterized by spectroscopic means. Structural diversity
      within cascarilla clerodanes involves mainly the linkage between the carbocyclic
      and the heterocyclic moieties and the functionalization of C-3, C-4, and C-6 of
      the decalin core. Cascarillin was shown to be a mixture of interconverting gamma
      lactols and not a gamma-hydroxyaldehyde as previously reported.

PMID- 12188621
TI  - Volatile compounds of Psidium salutare (H.B.K.) Berg. fruit.
AB  - Volatile compounds were isolated from Psidium salutare fruits by simultaneous
      steam distillation-solvent extraction according to the Likens-Nickerson
      procedure. Compounds were identified by capillary GC and GC-MS. One hundred and
      fifty compounds were identified in the aroma concentrate, from which limonene,
      myrcene, and alpha-pinene were found to be the major constituents in the fruit.

PMID- 12188622
TI  - Flavor release and perception of flavored whey protein gels: perception is
      determined by texture rather than by release.
AB  - Five whey protein gels, with different gel hardnesses and waterholding
      capacities, were flavored with ethylbutyrate or diacetyl and evaluated by a 10
      person panel to study the relation between the gel structure and the sensory
      perception, as well as the nosespace flavor concentration during eating. The
      sensory perception of the flavor compounds was measured by the time-intensity
      method, while simultaneously the nosespace flavor concentration was monitored by
      the MS-Nose. The nosespace flavor concentration was found to be independent of
      the gel hardness or waterholding capacity. However, significant changes in flavor
      intensity between the gels were perceived by the majority of the panelists,
      despite the fact that the panelists were instructed to focus only on flavor
      perception and to not take texture into account. From these observations it is
      concluded that the texture of gels determines perception of flavor intensity
      rather than the in-nose flavor concentration.

PMID- 12188623
TI  - Quantitative model studies on the efficiency of precursors in the formation of
      cooling-active 1-pyrrolidinyl-2-cyclopenten-1-ones and bitter-tasting cyclopenta
      [b]azepin-8(1H)-ones.
AB  - The yields of the cooling-active compounds 3-methyl-2-(1-pyrrolidinyl)-2
      cyclopenten-1-one (1) and 5-methyl-2-(1-pyrrolidinyl)-2-cyclopenten-1-one (2) as
      well as the bitter tastants 7-methyl-2,3,6,7-tetrahydrocyclopenta-[b]azepin-8(1H)
      one (3) and 7-methyl-2,3,4,5,6,7-hexahydrocyclopenta-[b]azepin-8(1H)-one (4)
      obtained by heating mixtures of possible Maillard-type precursors in model
      systems varying in temperature, pH value, or water content were determined
      quantitatively. The results showed that hexose-derived cyclotene is the common
      precursor for all four tastants and that the formation of each individual tastant
      is strongly determined by the structure of the nitrogen-containing precursor,
      e.g., reaction of cyclotene with pyrrolidine formed by thermal decarboxylation of
      L-proline produced the cooling compounds 1 and 2 only, whereas in the presence of
      1-pyrroline formed upon Strecker reactions of L-proline, the bitter tasting
      azepinone 3 was produced exclusively. In contrast, the structure of the secondary
      amino acid L-proline enabled the formation of compound 4, whereas the pyrrolidine
      and 1-pyrroline, respectively, do not generate this tastant. In addition, a
      nonvolatile, tasteless intermediate, (S)-3-methyl-2-[(2'-carboxy)-1-pyrrolidinyl]
      2-cyclopenten-1-one (5), was isolated from the cyclotene/L-proline reaction
      mixture and could be confirmed as an efficient precursor for the cooling compound
      1. The data, obtained by these studies, are the scientific basis to tailor the
      desired overall flavor of foods by means of a more controlled Maillard-type
      technology.

PMID- 12188624
TI  - Agaricus blazei (class Basidiomycotina) aqueous extract enhances the expression
      of c-Jun protein in MCF7 cells.
AB  - The edible mushroom Agaricus blazei Murill is considered a health food in many
      countries after it was reported to be a source of antitumor and immunoactive
      compounds. An aqueous extract (AE) from this basidiomycete significantly enhanced
      the expression of the c-Jun/activator protein-1 (AP1) in the human breast cancer
      cell line MCF7. Incubating the cells with 17-beta-estradiol (E2), p-nonylphenol
      (NP), and the AE combined, or NP plus the AE, resulted in increased cell
      proliferation compared to the untreated control by 93 and 67%, respectively.
      However, incubating the cells with the extract alone did not enhance cell
      division. It is suggested that the enhanced proliferation of MCF7 cells in the
      presence of NP and the AE may be due to the involvement of an AP1 gene regulatory
      complex. This is the first report showing enhanced c-Jun/AP1 expression in MCF7
      cells incubated with an aqueous fungal extract.

PMID- 12188625
TI  - Chitosan as an edible invisible film for quality preservation of herring and
      atlantic cod.
AB  - The effect of chitosan with different molecular weights as coatings for shelf
      life extension of fresh fillets of Atlantic cod (Gadus morhua) and herring
      (Clupea harengus) was evaluated over a 12-day storage at refrigerated temperature
      (4 +/- 1 degrees C). Three chitosan preparations from snow crab (Chinoecetes
      opilio) processing wastes, differing in viscosities and molecular weights, were
      prepared; their apparent viscosities (360, 57, and 14 cP) depended on the
      deacetylation time (4, 10, and 20 h, respectively) of the chitin precursor. Upon
      coating with chitosans, a significant (p < or = 0.05) reduction in relative
      moisture losses of 37, 29, 29, 40, and 32% was observed for cod samples coated
      with 360 cP chitosan after 4, 6, 8, 10, and 12 days of storage, respectively.
      Chitosan coating significantly (p < or = 0.05) reduced lipid oxidation as
      displayed in peroxide value, conjugated dienes, 2-thiobarbituric acid reactive
      substances and headspace volatiles, chemical spoilage as reflected in total
      volatile basic nitrogen, trimethylamine, and hypoxanthine, and growth of
      microorganisms as reflected in total plate count in both fish model systems
      compared to uncoated samples. The preservative efficacy and the viscosity of
      chitosan were inter-related; the efficacy of chitosans with viscosities of 57 and
      360 cP was superior to that of chitosan with a 14 cP viscosity. Thus, chitosan as
      edible coating would enhance the quality of seafoods during storage.

PMID- 12188626
TI  - Characterization and functional properties of lactosyl caseinomacropeptide
      conjugates.
AB  - Ovine caseinomacropeptide (CMP) was modified with lactose through Maillard
      reaction under 44% relative humidity and 40 degrees C for various periods (0-11
      days). Different lactosylated CMP forms were separated by capillary
      electrophoresis and reversed phase high-performance liquid chromatography (RP
      HPLC) and identified by RP-HPLC coupled with electrospray ionization mass
      spectrometry (ESI-MS). Around 55-60% of CMP was lactosylated under the conditions
      assayed, with the monolactosylated form being the most abundant one, followed by
      the di-, tri-, and tetralactosylated species. During the first days of incubation
      amino acid analyses showed a decrease in lysine and NH(2)-terminal methionine,
      which coincided with an increase in the furosine content. However, from the ninth
      day of incubation, further degradation of Amadori compounds prevailed over their
      formation. Solubility, heat stability, and emulsifying capacity of the native and
      modified CMP were investigated. Lactosylation improved the emulsifying activity,
      but it did not modify the great solubility and heat stability of native CMP.

PMID- 12188627
TI  - Isolation and structure elucidation of a new thermal breakdown product of
      glucobrassicin, the parent indole glucosinolate.
AB  - The thermal breakdown of glucobrassicin, the major natural indole glucosinolate
      present in cruciferous vegetables, has been studied. This study has been
      conducted using pure synthetic glucobrassicin instead of raw vegetable material
      to eliminate possible other sources (i.e., enzymatic or chemical) of degradation.
      After 1 h in aqueous solution at 100 degrees C, 10% of the original
      glucobrassicin is degraded and yields a unique degradation compound. This
      compound is described for the first time and has been identified as 2-(3'
      indolylmethyl)glucobrassicin on the basis of data obtained by (1)H nuclear
      magnetic resonance spectroscopy as well as tandem mass spectrometric experiments
      carried out from positive and negative electrospray produced ions.

PMID- 12188629
TI  - Effect of freezing and storage on the phenolics, ellagitannins, flavonoids, and
      antioxidant capacity of red raspberries.
AB  - Scottish-grown red raspberries are a rich source of vitamin C and phenolics, most
      notably, the anthocyanins cyanidin-3-sophoroside, cyanidin-3-(2(G)
      glucosylrutinoside), and cyanidin-3-glucoside, and two ellagitannins, sanguiin H
      6 and lambertianin C, which are present together with trace levels of flavonols,
      ellagic acid, and hydroxycinnamates. The antioxidant capacity of the fresh fruit
      and the levels of vitamin C and phenolics were not affected by freezing. When
      fruit were stored at 4 degrees C for 3 days and then at 18 degrees C for 24 h,
      mimicking the route fresh fruit takes after harvest to the supermarket and onto
      the consumer's table, anthocyanin levels were unaffected while vitamin C levels
      declined and those of elligitannins increased, and overall, there was no effect
      on the antioxidant capacity of the fruit. It is concluded, therefore, that
      freshly picked, fresh commercial, and frozen raspberries all contain similar
      levels of phytochemicals and antioxidants per serving.

PMID- 12188628
TI  - Ellagitannins, flavonoids, and other phenolics in red raspberries and their
      contribution to antioxidant capacity and vasorelaxation properties.
AB  - Analysis of extracts of Glen Ample raspberries (Rubus idaeus L.) by gradient,
      reverse phase HPLC with diode array and tandem mass spectrometry identified
      eleven anthocyanins, including cyanidin-3-sophoroside, cyanidin-3-(2(G)
      glucosylrutinoside), cyanidin-3-glucoside, cyanidin-3-rutinoside, pelargonidin-3
      sophoroside, pelargonidin-3-(2(G)-glucosylrutinoside), and pelargonidin-3
      glucoside. Significant quantities of an ellagitannin, sanguiin H-6, with an M(r)
      of 1870 were detected along with lower levels of a second ellagitannin,
      lambertianin C, which has an M(r) of 2804. Other phenolic compounds that were
      detected included trace levels of ellagic acid and its sugar conjugates along
      with one kaempferol- and four quercetin-based flavonol conjugates. Fractionation
      by preparative HPLC revealed that sanguiin H-6 was a major contributor to the
      antioxidant capacity of raspberries together with vitamin C and the anthocyanins.
      Vasodilation activity was restricted to fractions containing lambertianin C and
      sanguiin H-6.

PMID- 12188630
TI  - Transport of amino acids from in vitro digested legume proteins or casein in Caco
      2 cell cultures.
AB  - Purified legume storage proteins (chickpea 11S and 7S globulins, faba bean
      globulins, and lupin globulins) and casein (casein) were subjected to an in vitro
      enzyme (pepsin + pancreatin) digestion process. Protein digests were then used in
      a bicameral Caco-2 cell culture system to determine amino acid transport across
      the cell monolayer. With digests from legume proteins, absolute amounts of
      aspartate, glycine, and arginine transported were higher than those found in
      digested casein, whereas amounts of glutamate, proline, tyrosine, valine, and
      lysine were lower. However, proportions of amino acids in the basolateral chamber
      as compared with amounts added in the apical chamber were lower than casein
      controls for all amino acids except cystine. Results confirm previous in vivo
      observations that amino acids from legume proteins are probably absorbed at rates
      different from those in other proteins of animal origin such as casein.

PMID- 12188631
TI  - Hydrophobic probe binding of beta-lactoglobulin in the native and molten globule
      state induced by high pressure as affected by pH, KIO(3) and N-ethylmaleimide.
AB  - High hydrostatic pressure (HHP) at 500 MPa and 50 degrees C induces beta-LG into
      the molten globule state. Retinol, cis-parinaric acid (CPA), and 1-anilino
      naphthalene-8-sulfonate (ANS) fluorescence from pH 2.5 to 10.5 in the presence of
      the native and molten globule states of beta-LG indicate that retinol binds to
      beta-LG in the calyx, CPA at the surface hydrophobic site, and ANS in multiple
      hydrophobic sites. HHP treatment results in a decrease of beta-LG affinity for
      retinol and CPA, suggesting conformational changes in the calyx and surface
      hydrophobic site of beta-LG during HHP treatment. beta-LG treated by HHP in the
      presence of N-ethylmaleimide (NEM) retains retinol affinity, suggesting that NEM
      protects the calyx conformation of beta-LG during HHP treatment. HHP treatment of
      beta-LG in the presence of KIO(3) exhibits a great decrease of CPA affinity
      compared to HHP-treated beta-LG in the absence of KIO(3), suggesting the
      formation of non-native disulfide bonding at the CPA binding site.

PMID- 12188632
TI  - Polyphenol-induced inhibition of the response of na(+)/glucose cotransporter
      expressed in Xenopus oocytes.
AB  - To study the effects of polyphenols on the Na(+)/glucose cotransporter (SGLT1)
      response, SGLT1 was expressed in Xenopus oocytes by injecting cRNA synthesized
      from the cloned cDNA of the small intestine cotransporter of rats, and the
      electrical response elicited by glucose or galactose was measured by a voltage
      clamping method. Most phenol derivatives had no effect on the response. However,
      the polyphenols (+)-catechin, (-)-epicatechin gallate (ECg), and (-)
      epigallocatechin gallate (EGCg), which are components of green tea, caused an
      inhibition of the response, which was almost independent of glucose
      concentration. The inhibition constants were estimated to be 2.3 mM for (+)
      catechin and 0.45 mM for both ECg and EGCg, assuming the noncompetitive
      inhibition mechanism. Saponin prepared from tea seeds also inhibited the response
      significantly. Tannic acid and aqueous extracts of teas induced nonspecific
      electrical responses in both cRNA-injected and noninjected oocytes at lower
      concentrations than those that caused an inhibition of the SGLT1 response when
      their dose-dependent effects were examined. These results are possibly helpful in
      the development of a dietary supplement for diabetic patients.

PMID- 12188633
TI  - Potential of peroxynitrite to alter the color of myoglobin in muscle foods.
AB  - Superoxide anion and nitric oxide can react to form the highly oxidizing species
      peroxynitrite. The objective of this research was to determine if peroxynitrite
      can promote the discoloration of myoglobin under conditions expected in muscle
      foods. Reagent peroxynitrite (25-100 microM) caused rapid and extensive formation
      of metmyoglobin from oxymyoglobin with the majority of metmyoglobin formation
      occurring during the first 5-10 min of incubation. Carbon dioxide caused a small
      decrease in the ability of peroxynitrite to oxidize oxymyoglobin, and
      peroxynitrite-promoted conversion of oxymyoglobin to metmyoglobin increased with
      decreasing pH (5.5-7.0). Differential scanning calorimetry suggested that
      peroxynitrite caused minimal changes in myoglobin structure. These results
      indicate that peroxynitrite can promote the conversion of oxymyoglobin to
      metmyoglobin under the conditions expected in muscle foods.

PMID- 12188634
TI  - Influence of fat crystallization on the stability of flocculated emulsions.
AB  - Various degrees of flocculation were induced in a 20 wt % n-hexadecane and
      confectionery-coating fat emulsion by adding xanthan gum (0-0.3 wt %). The
      emulsions were temperature cycled (40 to -10 to 40 to -10 degrees C) in a
      differential scanning calorimeter. The emulsified and de-emulsified fat
      crystallized at different temperatures, and the ratio of the two enthalpies was
      used to calculate the proportion of de-emulsified fat and hence the extent of
      breakdown of the emulsion. The n-hexadecane droplets were stable to temperature
      cycling, whereas the confectionery-coating fat destabilized to a greater or
      lesser extent. The maximum destabilization of the confectionery-coating fat
      occurred at those concentrations of xanthan required to induce creaming.

PMID- 12188635
TI  - Bioavailability of zinc from cooked philippine milled, undermilled, and brown
      rice, as assessed in rats by using growth, bone zinc, and zinc-65 retention.
AB  - The nutritional bioavailability of zinc from cooked milled, undermilled, and
      brown Philippine rice (variety PSB Rc14) was evaluated in rats, comparing results
      based on weight gain, tibia zinc incorporation (slope ratio analyses), and zinc
      radiotracer retention. Milling reduced the phytic acid and mineral content of the
      rice, resulting in zinc concentrations of 16.5, 19.4, and 27.2 microg/g and
      phytate/zinc molar ratios of 4, 20, and 28 for milled, undermilled, and brown
      rice, respectively. Measured zinc bioavailability was similar whether using
      growth, bone zinc, or radioisotope retention as criteria, at approximately 92,
      86, and 77% of zinc sulfate, for milled, undermilled, and brown rice,
      respectively. However, the higher percent bioavailability of the zinc after
      milling was insufficient to compensate for the lower zinc content. With respect
      to zinc, the nutritional value was inversely related to milling, providing
      approximately 15, 17, and 21 microg bioavailable zinc/g rice, respectively, for
      milled, undermilled and brown rice of this variety.

PMID- 12188636
TI  - Characterization of resistant starch type III from banana (Musa acuminata).
AB  - Banana starch (Musa acuminata var. Nandigobe) was evaluated for its use in
      generating resistant starch (RS) type III. Structural, physicochemical, and
      biological properties of these products were analyzed. The investigated process
      includes debranching of the native starch and retrogradation under different
      storage temperatures and starch concentrations. After enzymatic debranching, a
      high amount of low-molecular-weight polymers with a degree of polymerization
      between 10 and 35 glucose units beside a higher molecular weight fraction were
      found. The resulting products comprised RS contents of about 50%. After heat
      moisture treatment, the RS yield increased up to 84%. Peak temperatures of about
      145 degrees C found in DSC measurements pointed to a high thermal stability of
      the RS products. In vitro fermentations of the RS products, carried out with
      intestinal microflora of healthy humans, resulted in a molar ratio of
      acetate:propionate:butyrate of about 49:17:34. The established method allowed the
      production of a high-quality RS with prebiotic properties for health preventing
      applications.

PMID- 12188637
TI  - Residue study of ivermectin in plasma, milk, and mozzarella cheese following
      subcutaneous administration to buffalo (Bubalus bubalis).
AB  - The distribution of ivermectin in buffalo plasma and milk after administration of
      a single subcutaneous dose (0.2 mg kg(-)(1) b.w.) was studied. Ivermectin reached
      the maximal concentration in plasma (28.5 +/- 1.7 ng mL(-)(1)) and milk (23.6 +/-
      2.6 ng mL(-)(1)) after 2.4 +/- 0.32 and 2.8 +/- 0.44 days, respectively. The drug
      showed a parallel disposition in milk and plasma, with a ratio of 1.12 +/- 0.16.
      Ivermectin concentrations were detected in mozzarella cheese obtained from milk
      collected on days 1, 3, 4, and 20 following administration. The highest values
      (81.4 +/- 3.26 ng g(-)(1)) were found in the cheese produced on day 3 and were 4
      fold higher than those present in the milk.

PMID- 12188638
TI  - Aflatoxin and fumonisin contamination of commercial corn (Zea mays) hybrids in
      Mississippi.
AB  - Resistance to mycotoxin contamination was compared in field samples harvested
      from 45 commercial corn (maize) hybrids and 5 single-cross aflatoxin-resistant
      germplasm lines in years with high and moderate heat stress. In high heat stress,
      mycotoxin levels were (4.34 +/- 0.32) x 10(3) microg/kg [(0.95-10.5 x 10(3)
      microg/kg] aflatoxins and 11.2 +/- 1.2 mg/kg (0-35 mg/kg) fumonisins in
      commercial hybrids and 370 +/- 88 microg/kg (140-609 microg/kg) aflatoxins and
      4.0 +/- 1.3 mg/kg (1.7-7.8 mg/kg) fumonisins in aflatoxin-resistant germplasm
      lines. Deoxynivalenol was detected (one-fourth of the samples, 0-1.5 mg/kg), but
      not zearalenone. In moderate heat stress, mycotoxin levels were 6.2 +/- 1.6
      microg/kg (0-30.4 microg/kg) aflatoxins and 2.5 +/- 0.2 mg/kg (0.5-4.8 mg/kg)
      fumonisins in commercial hybrids and 1.6 +/- 0.7 microg/kg (0-7 microg/kg)
      aflatoxins and 1.2 +/- 0.2 mg/kg (0.5-3.0 mg/kg) fumonisins in aflatoxin
      resistant germplasm lines. The results are consistent with heat stress playing an
      important role in the susceptibility of corn to both aflatoxin and fumonisin
      contamination, with significant reductions of both aflatoxins and fumonisins in
      aflatoxin-resistant germplasm lines.

PMID- 12188639
TI  - Toward an RNaseA mimic: A DNAzyme with imidazoles and cationic amines.
AB  - Site-specific RNA cleavage has received considerable attention over the years.
      Directed synthesis to append imidazoles or amines or both to oligonucleotides to
      target specific RNA cleavage represents an exciting avenue of research. However,
      to date catalysis by such synthetic constructs, particularly in terms of
      turnover, has been difficult to observe. This is the first report of a truly
      catalytic M2+-independent DNAzyme synthetically modified with imidazoles and
      cationic amines that would seem to mimic RNaseA. This work now demonstrates how
      synthetic organic chemistry, when merged with combinatorial selection, can result
      in a new class of DNAzymes that meets the ongoing synthetic challenges for
      developing relatively small biomimetic catalysts.

PMID- 12188640
TI  - 2,4-Disila-1-germatricyclo[2.1.0.0(2,5)]pentane: a new type of cage compound of
      group 14 elements with an extremely long Ge-C bridge bond and an "Umbrella"-type
      configuration of a Ge atom.
AB  - The thermolysis of 1,1,2,3-tetrakis[di-tert-butyl(methyl)silyl]-4-phenyl-1,2
      disila-3-germacyclopenta-2,4-diene 1 at 175 degrees C results in the quantitative
      formation of 1,2,3,4-tetrakis[di-tert-butyl(methyl)silyl]-5-phenyl-2,4-disila-1
      germatricyclo[2.1.0. 02,5]pentane 2, representing a new type of cage compound of
      group 14 elements. The crystal structure of 2 was established by X-ray
      crystallography, which showed an extremely long Ge-C bridge bond of 2.242(3) A
      and an "umbrella"-type configuration of the Ge atom. The compound 2 readily
      reacted with benzaldehyde to produce 1,4,5,7-tetrakis[di-tert-butyl(methyl)silyl]
      3,6-diphenyl-2-oxa-1,4-disila-5-germabicyclo[2.2.1]hept-5-ene 3 with an
      endocyclic Ge=C double bond.

PMID- 12188642
TI  - beta(2,2)-Aminoxy acids: a new building block for turns and helices.
AB  - The conformational properties of peptides 1-4 built from 3-aminoxy-2,2-dimethyl
      propionic acid, a beta2,2-aminoxy acid, were investigated by NMR spectroscopy and
      X-ray crystallography. A novel beta N-O turn involving a nine-membered-ring
      intramolecular hydrogen bond between NHi+2 and COi was formed in diamides 1 and
      2, which was further stabilized by another six-membered-ring intramolecular
      hydrogen bond between NHi+2 and NOi+1. Triamides 3 and 4 displayed a well-defined
      helical structure featuring two consecutive beta N-O turns. The X-ray structure
      of 4 revealed that the amide carbonyl group at position i+2 was twisted +65.9
      degrees from that at i position, suggesting a novel 1.79 helix. Therefore,
      beta2,2-aminoxy acid can be used as a new building block for turns and helices.

PMID- 12188641
TI  - Highly enantioselective darzens reaction of a camphor-derived sulfonium amide to
      give glycidic amides and their applications in synthesis.
AB  - The reaction of an amide-stabilized sulfonium ylide bearing chiral groups on
      sulfur has been investigated. We have discovered that the camphor-derived amide
      stabilized ylide reacts with aldehydes at -50 degrees C in ethanol to give
      glycidic amides in one step with up to 99% ee and complete diastereoselectivity.
      From analyzing reactions of different ratios of diastereomers at sulfur it was
      found that the major diastereomer gave very high enantioselectivity, while the
      minor one gave much lower selectivity (54% ee). Further mechanistic studies have
      revealed that enantioselectivity is controlled not in the betaine-forming step (C
      C bond formation is reversible) but in the different barriers to bond rotation
      around the newly formed C-C of the two diastereomeric betaines. Further
      transformations of epoxyamides were investigated. It was found that epoxyamides
      could be converted into epoxyketones by reaction with organolithium reagents and
      that they could be ring-opened by nucleophiles with complete regioselectivity
      using Yb(OTf)3. The practicality of the process has been exemplified in the
      synthesis of SK&F 104353, a leukotriene D4 antagonist in the potential treatment
      of bronchial asthma.

PMID- 12188643
TI  - New natural product families from an environmental DNA (eDNA) gene cluster.
AB  - Uncultured bacteria represent a potentially rich source of new and useful natural
      products. Studying these natural products requires the development of effective
      yet straightforward methods to access the small-molecule chemical diversity
      produced by uncultured bacteria. In this study, DNA extracted directly from soil
      samples (environmental DNA, eDNA) was used to construct cosmid libraries in
      Escherichia coli, and these clones were then assayed for the production of
      antibiosis. A 13 open reading frame (ORF) biosynthetic gene cluster (feeA-M)
      found in one of the antibacterial active clones, CSLC-2, confers to E. coli the
      production of two new families of natural products that are derived from long
      chain N-acyltyrosines. The fee gene cluster and three families of the long chain
      acyl phenols derived from tyrosine (families 1, 2, and 3) are described.

PMID- 12188644
TI  - Mononuclear nitrogen/sulfur-ligated zinc methoxide and hydroxide complexes:
      investigating ligand effects on the hydrolytic stability of zinc alkoxide
      species.
AB  - The synthesis and properties of mononuclear zinc methoxide ([(ebnpa)Zn-OCH3]ClO4)
      (1) and hydroxide ([(ebnpa)Zn-OH]ClO4) (2) complexes of a new mixed
      nitrogen/sulfur ligand (ebnpa = N-2-(ethylthio)ethyl-N,N-bis(6-neopentylamino-2
      pyridylmethyl)amine) are reported. The structures of 1 and 2 were determined by X
      ray diffraction. Each possesses a single zinc-coordinated anion (methoxide or
      hydroxide) and exhibits an overall trigonal bipyramidal geometry. Structural and
      spectroscopic studies indicate the presence of two hydrogen-bonding interactions
      involving the oxygen atom of the zinc-bound anion in each complex. Treatment of
      [(ebnpa)Zn-OH]ClO4 with CH3OH results in the formation of an equilibrium mixture
      of 1 and 2. 1H NMR spectroscopic methods were used to examine the equilibrium as
      a function of temperature, yielding KMe (304 K) = 0.30(8), DeltaHMe = -0.9(1)
      kcal/mol, and DeltaSMe = -5(1) eu. The negative enthalpy indicates that
      spontaneous zinc alkoxide formation from a hydroxide precursor occurs in this
      system at low temperature. Using the experimentally determined DeltaHMe value, we
      found the homolytic Zn-O bond dissociation energy (BDE) in the Zn-OCH3 unit to be
      approximately -14 kcal/mol relative to the Zn-O BDE in the Zn-OH unit.

PMID- 12188645
TI  - In vitro selection of mRNA display libraries containing an unnatural amino acid.
AB  - The incorporation of unnatural amino acid into selectable, amplifiable peptide
      and protein libraries expands the chemical diversity of such libraries, thus
      considerably facilitating the process of obtaining ligands with improved
      properties (affinity, specificity, and function), particularly against
      therapeutically interesting targets. Here, we report that biocytin, a biotin
      derivative of lysine, can be inserted into an mRNA-protein fusion molecule
      through amber stop codon suppression. We also demonstrate that templates
      containing the codon corresponding to the biocytin tRNA (a UAG stop codon) can be
      enriched by iterative cycles of selection against a streptavidin agarose matrix.

PMID- 12188646
TI  - Asymmetric total synthesis of dendrobatid alkaloid 251F.
AB  - The dendrobatid alkaloid (-)-251F was synthesized. The key steps of the synthesis
      were (1) an asymmetric Diels-Alder reaction to establish four of the necessary
      stereocenters in the target, (2) a ring-opening/ring-closing metathesis reaction
      to establish a key [3.3.0] bicyclic intermediate, and (3) an intramolecular
      Schmidt reaction.

PMID- 12188647
TI  - Synthesis, structure, and reactions of a three-coordinate nickel-carbene complex,
      [1,2-Bis(di-tert-butylphosphino)ethane]Ni=CPh(2).
AB  - The three-coordinate nickel-carbene complex (dtbpe)Ni=CPh2 (3) was prepared from
      the thermolysis of the diphenyldiazoalkane complex (dtbpe)Ni(N,N':eta2-N2CPh2)
      (2) (dtbpe = 1,2-bis(di-tert-butylphosphino)ethane). Complex 3 was structurally
      characterized by single-crystal X-ray diffraction methods (Ni-C = 1.836(2) A).
      Complex 3 reacts with 2 equiv of CO2 to afford (dtbpe)Ni{OC(O)CPh2C(O)O} (4),
      with diphenylketene to give (dtbpe)Ni{OC(=CPh2)CPh2} (5), with excess CO to
      transfer the carbene fragment and generate diphenylketene and (dtbpe)Ni(CO)2 (6),
      with sulfur dioxide to give the metallasulfone (dtbpe)Ni{C,S:eta2-S(O)2CPh2} (7),
      and with the Bronsted acid [HNMe2Ph][B(C6F5)4] to give the alkyl cation
      [(dtbpe)Ni(CHPh2)][B(C6F5)4] (8). Complexes 4, 5, and 7 have also been
      characterized by single-crystal X-ray diffraction methods.

PMID- 12188648
TI  - High charge carrier mobility in conjugated organometallic polymer networks.
AB  - The improvement of charge transport in conjugated polymers is a focal point of
      current research. It is shown here that the carrier mobility can be substantially
      increased through the introduction of conjugated cross-links between the
      conjugated chains. Novel organometallic polymer networks based on a poly(p
      phenylene ethynylene) (PPE) derivative and Pt0 were synthesized by ligand
      exchange reactions between the linear PPE and a low-molecular Pt complex. Time-of
      flight measurements revealed ambipolar charge carrier mobilities of up to 1.6 x
      10-2 cm2 V-1 s-1 for these materials, which are an order of magnitude higher than
      those of the neat polymer and represent the highest mobilities yet observed in
      disordered conjugated polymers.

PMID- 12188649
TI  - Control of the anchoring behavior of polymer-dispersed liquid crystals: effect of
      branching in the side chains of polyacrylates.
AB  - A temperature-driven anchoring transition in a polymer/nematic fluid composite
      that is far from the bulk nematic-isotropic transition temperature is reported. A
      series of poly(methylheptyl acrylates) were studied to probe the subtle effects
      of the side chain structure of the polymer on control of the anchoring. A polymer
      dispersed liquid crystal film made from TL205 and 1-methylheptyl acrylate shows
      only planar anchoring over the temperature range studied, while the films made
      from TL205 and each of the other methylheptyl acrylates or n-heptyl acrylate show
      the homeotropic-to-planar anchoring transition at temperatures between 70 and 78
      degrees C. An interfacial model is proposed in which the different conformation
      of the side chains is suggested as the cause for the dramatic difference in the
      observed anchoring behavior.

PMID- 12188650
TI  - Dual-action molecular superconductors with magnetic anions.
AB  - Dual-action organic superconductors, whose conducting properties can be sharply
      controlled by an external magnetic field, have been discovered in systems
      consisting of organic conduction layers based on
      bis(ethylenedithio)tetraselenafulvalene (BETS) molecules and magnetic anions.
      Owing to the metamagnetic nature of the anion layers, the superconducting state
      of kappa-BETS2FeBr4 can be switched on or off by applying the external field. In
      lambda-BETS2Fe0.4Ga0.6Cl4, exhibiting a field-induced superconducting transition
      for the field parallel to the conduction plane, the insulating, metallic, and
      superconducting states can be realized in a stepwise manner by slightly tuning
      the external magnetic field.

PMID- 12188651
TI  - Epitope mapping of ligand-receptor interactions by diffusion NMR.
AB  - A novel method based on diffusion NMR for the epitope mapping of ligand binding
      is presented. The intermolecular NOE builds up during a long diffusion period and
      creates a deviation from the linearity. The ligand proton nearest the protein
      generates the strongest NOE from protein during the diffusion period and has the
      largest deviation. Therefore, this diffusion artifact can be used to characterize
      the ligand binding epitope. The concept was investigated using dihydrofolate
      reductase (DHFR) and its ligand trimethoprim (TMP), and the epitope map of TMP on
      DHFR generated with this method is in excellent agreement with the structural and
      dynamic studies by crystallography and NMR, as well as the medicinal chemistry
      results.

PMID- 12188652
TI  - Physical interpretation of residual dipolar couplings in neutral aligned media.
AB  - A novel method is described for rapidly calculating alignment tensors from
      hydrodynamic shape, required for the prediction of residual dipolar couplings in
      neutral aligned media. Simulations of alignment were used to show that for steric
      restriction at a planar surface, the alignment process is dependent on linear
      hydrodynamic length. However, as discussed, previous methods are not in agreement
      with this observation. Therefore, the method presented here is the first to
      provide simple, accurate predictions of the alignment tensor for neutral and
      dilute media, while being consistent with simulations of alignment. It provides
      predictions in a fraction of the time of a simulation approach, while aiding
      physical intuition by providing a direct link between shape and alignment. Not
      only is this physically gratifying, but it also permits residual dipolar
      couplings to be applied in demanding situations where simulations of alignment
      are not desirable, such as in studies of molecular dynamics.

PMID- 12188653
TI  - Tetrakis(2-hydroxyphenyl)ethene and derivatives. A structurally preorganized
      tetradentate ligand system for polymetallic coordination chemistry and catalysis.
AB  - A topologically unique, conformationally constrained tetradentate ligand system
      for polymetallic coordination chemistry has been developed: tetrakis(2
      hydroxyphenyl)ethene (1a) and substituted derivatives. The design exploits the
      planarity of the tetraphenylethylene core to impart rigidity to the roughly
      square oxygen binding array, while maintaining a degree of conformational
      mobility associated with rotation about the aryl-ethylene carbon-carbon bonds.
      Tetrakis(2-hydroxyphenyl)ethene derivatives are designed to promote multiple
      metal bridging over chelating coordination modes. The ligand is synthesized from
      anisole or 4-tert-butylanisole in four steps via the 2,2'-dimethoxybenzophenone
      hydrazones 4a,b. The sterically hindered ortho-substituted tetraphenylethylene
      core is produced in high yield by acid-catalyzed decomposition of the
      corresponding diaryl diazomethane prepared in situ by oxidation of the hydrazone
      using nickel peroxide. Deprotection of the methyl ethers using boron tribromide
      gives tetrakis(2-hydroxyphenyl)ethene (1a), characterized by X-ray
      crystallography, and tetrakis(5-tert-butyl-2-hydroxyphenyl)ethene (1b).
      Sterically isolating substituents in the 3-position can be installed via Claisen
      rearrangement/hydrogenation, providing tetrakis(3-n-propyl-2-hydroxyphenyl)ethene
      (6) efficiently. To illustrate potential applications of this unprecedented
      ligand class, two coordination complexes are reported, including tetrakis(2
      diethylaluminoxyphenyl)ethene (8), a structurally robust eight-membered-ring
      aluminum/oxygen crown complex characterized both in solution and in the solid
      state.

PMID- 12188654
TI  - Supramolecular isomerism in coordination compounds: nanoscale molecular hexagons
      and chains.
AB  - A nanoscale supramolecular hexagon, 1, and its supramolecular isomeric chain
      structure, 2, have been prepared from self-assembly of 5-NO2-bdc and Cu(II)
      cations. The hexagon is neutral and soluble and has outer and inner diameters of
      3.1 and 0.8 nm, respectively.

PMID- 12188655
TI  - Broad-spectrum enantioselective diels-alder catalysis by chiral, cationic
      oxazaborolidines.
AB  - The cationic chiral Lewis acids 1 and 2, generated by triflic acid protonation of
      the corresponding neutral oxazaborolidines, serve as excellent catalysts for
      Diels-Alder addition of cyclopentadiene to a wide variety of dienophiles. Adducts
      have been obtained in excellent yield and enantioselectivity from alpha,beta
      unsaturated esters, lactones, and cyclic ketones. The absolute facial selectivity
      for each of these substrates follows a common pattern which differs from that
      observed with alpha,beta-enals. The different reaction channels can be understood
      in terms of pathways via complexes 3 (for alpha,beta-enals) and 4 (for alpha,beta
      enones and esters).

PMID- 12188656
TI  - A new ruthenium complex with an electron-donating aminoindenyl ligand for fast
      metal-mediated living radical polymerizations.
AB  - A new ruthenium complex with an electron-donating aminoindenyl ligand induces a
      fast living radical polymerization of methyl methacrylate (MMA) in the presence
      of a chloride initiator to give polymers with controlled and variable molecular
      weights (Mn = 103-105) and very narrow molecular weight distributions (Mw/Mn <
      1.1). The structure and high activity of the catalyst were analyzed by X-ray
      crystallography and cyclic voltammetry in comparison to those of a similar
      complex with an indenyl ligand.

PMID- 12188657
TI  - Reversible polymerization driven by folding.
AB  - Bisfunctionalized m-phenylene ethynylene imine oligomers were polymerized in the
      polar solvent acetonitrile, resulting in high-molecular weight poly(m-phenylene
      ethynylene imine)s. It is hypothesized that this polymerization, which proceeds
      through the reversible metathesis of imine bonds, is driven by the folding of the
      long m-phenylene ethynylene imine chains. Upon conducting the polymerization in a
      series of solvents in which the m-phenylene ethynylene oligomers exhibit
      different folding stabilities, it was possible to correlate the molecular weight
      of the resulting poly(m-phenylene ethynylene imine)s with the helical stability
      of the corresponding oligomers. The polymerization was also demonstrated to be
      reversible and responsive to solvent and temperature changes.

PMID- 12188658
TI  - Long-range self-assembly of a polyunsaturated linear organosilane at the n
      tetradecane/Au(111) interface studied by STM.
AB  - We report on the formation of self-assembled monolayers of 13-(trimethylsilyl)-1
      tridecene-6,12-diyne [C13H17-Si(CH3)3], an organosilane derivative with a linear
      polyunsaturated chain, on Au(111) substrates. Molecular resolution STM images
      recorded at the liquid-solid interface between gold and tetradecane reveal a long
      range and densely packed hexagonal lattice with a ( radical3 x radical3)R30
      degrees -like structure commensurate against gold adlattice.

PMID- 12188660
TI  - A conducting crystal based on a single-component paramagnetic molecule,
      [Cu(dmdt)(2)] (dmdt = dimethyltetrathiafulvalenedithiolate).
AB  - A single-component conducting molecular crystal composed of paramagnetic copper
      complexes, [Cu(dmdt)2]0+, was prepared. The crystal has an unprecedented three
      dimensionally packed molecular arrangement and exhibits a fairly high
      conductivity (1 S cm-1 at room temperature). The magnetic susceptibility
      measurements revealed that [Cu(dmdt)2]0+ molecule keeps most of S = 1/2 spin
      moments. The difference of the bond lengths between [Cu(dmdt)2]0+ and
      [Cu(dmdt)2]2- is consistent with the result of the molecular orbital calculation.

PMID- 12188659
TI  - Non-oxidative decarboxylation of glycine derivatives by a peroxidase.
AB  - Under anaerobic, peroxide-free conditions (pH 5.5, 25 degrees C), horseradish
      peroxidase (HRP) catalyzes the rapid, non-oxidatve decarboxylation of N-alkyl-N
      phenylglycine derivatives to the corresponding N-alkyl-N-methylanilines in 100%
      yield. When the reaction is conducted in D2O buffer, the product contains a
      single deuterium in the methyl group. The reactions are very fast compared to the
      oxidative decarboxylation of the same substrates under standard peroxidatic
      conditions (i.e., hydrogen peroxide added, air present) and in fact are inhibited
      by peroxide and oxygen. To account for these unprecedented observations, we
      propose a cyclic mechanism in which ferric HRP abstracts an electron from the
      substrate, giving an aminium ion intermediate that decarboxylates; protonation of
      the resulting alpha-aminoradical on carbon gives an aminium ion that is reduced
      by ferrous HRP to complete the cycle.

PMID- 12188662
TI  - Enantioselective addition of amines to ketenes catalyzed by a planar-chiral
      derivative of PPY: possible intervention of chiral Bronsted-acid catalysis.
AB  - The first method for the catalytic enantioselective addition of amines
      (specifically, pyrroles) to ketenes has been developed, and it has been
      demonstrated that the resulting acylpyrroles can be transformed into a broad
      spectrum of useful derivatives. On the basis of mechanistic studies, it is
      suggested that the planar-chiral catalyst plays an unanticipated role in this
      process as a chiral Bronsted acid.

PMID- 12188661
TI  - Modulating ion channel properties of transmembrane peptide nanotubes through
      heteromeric supramolecular assemblies.
AB  - A selective heteromeric supramolecular assembly process is devised to create
      functional single channels of altered ion conductance, charge selectivity, and
      rectification. The hollow transmembrane tubular structure produced spontaneously
      from the self-assembly of cyclic-d,l-alpha-peptides in lipid bilayers is modified
      by designer cyclic peptide "cap" subunits that bind site-selectively at the mouth
      of the channel assembly.

PMID- 12188663
TI  - Novel Catalytic CO(2) Incorporation Reaction: Nickel-Catalyzed Regio- and
      Stereoselective Ring-Closing Carboxylation of Bis-1,3-dienes.
AB  - Novel nickel-catalyzed carboxylation of bis-1,3-dienes using carbon dioxide (CO2)
      was investigated. In the presence of catalytic amounts of Ni(acac)2 and PPh3,
      various bis-1,3-dienes smoothly reacted with CO2 and an organozinc reagent
      (Et2Zn, Me2Zn, or Ph2Zn) under mild conditions. This catalytic carboxylation
      process was accompanied by carbocyclization of bis-1,3-diene followed by
      alkylation by an organozinc reagent to afford cyclic carboxylic acid derivatives
      in high yields with high regio- and stereoselectivities.

PMID- 12188665
TI  - Structure-based analysis and optimization of a highly enantioselective catalyst
      for the strecker reaction.
AB  - A mechanistic investigation of the asymmetric Strecker reaction catalyzed by a
      metal-free Schiff base catalyst was conducted. The active site of the catalyst,
      the relevant stereoisomer of the imine substrate, and the solution structure of
      the imine-catalyst complex were elucidated using a series of kinetics, structure
      activity, and NMR experiments. An unusual bridging interaction between the imine
      and the urea hydrogens of the catalyst was identified and supported by
      computation. Rational optimization of catalyst structure based on the mechanistic
      insight led to an improved catalyst for the asymmetric Strecker reaction.

PMID- 12188664
TI  - Enantioselective synthesis without discrete optically active additives.
AB  - By an adaptation of the asymmetric autocatalysis reactions of Soai, it was found
      that small enantiomeric excesses may be amplified to an arbitrary extent. When
      this process was applied 48 times to reactions in the absence of discrete
      optically active additives, all ultimately afforded substantial optical activity
      in the product. However, observations strongly suggest that most (and likely all)
      of these reactions are not true examples of absolute asymmetric synthesis.
      Rather, the ultimate optical activity arises from optically active impurities.
      Trace amounts of optically active materials may dominate the outcome of reactions
      involving asymmetric autocatalysis, and in the presence of opposite chiral
      influences a single enantiomer tends to take over a reaction. The possible
      implications of these observations to the origin of biological homochirality are
      noted.

PMID- 12188666
TI  - The active site of cellobiohydrolase Cel6A from Trichoderma reesei: the roles of
      aspartic acids D221 and D175.
AB  - Trichoderma reesei cellobiohydrolase Cel6A is an inverting glycosidase.
      Structural studies have established that the tunnel-shaped active site of Cel6A
      contains two aspartic acids, D221 and D175, that are close to the glycosidic
      oxygen of the scissile bond and at hydrogen-bonding distance from each other.
      Here, site-directed mutagenesis, X-ray crystallography, and enzyme kinetic
      studies have been used to confirm the role of residue D221 as the catalytic acid.
      D175 is shown to affect protonation of D221 and to contribute to the
      electrostatic stabilization of the partial positive charge in the transition
      state. Structural and modeling studies suggest that the single-displacement
      mechanism of Cel6A may not directly involve a catalytic base. The value of
      (D2O)(V) of 1.16 +/- 0.14 for hydrolysis of cellotriose suggests that the large
      direct effect expected for proton transfer from the nucleophilic water through a
      water chain (Grotthus mechanism) is offset by an inverse effect arising from
      reversibly breaking the short, tight hydrogen bond between D221 and D175 before
      catalysis.

PMID- 12188667
TI  - Four-dimensional NMR spectroscopy of a 723-residue protein: chemical shift
      assignments and secondary structure of malate synthase g.
AB  - A four-dimensional (4-D) NMR study of Escherichia coli malate synthase G (MSG), a
      723-residue monomeric enzyme (81.4 kDa), is described. Virtually complete
      backbone (1)HN, (15)N, (13)C, and (13)C(beta) chemical shift assignments of this
      largely alpha-helical protein are reported. The assignment strategy follows from
      our previously described approach based on TROSY triple resonance 4-D NMR
      spectroscopy [Yang, D.; Kay, L. E. J. Am. Chem. Soc. 1999, 121, 2571-2575.
      Konrat, R; Yang, D; Kay, L. E. J. Biomol. NMR 1999, 15, 309-313] with a number of
      modifications necessitated by the large size of the protein. A protocol for
      refolding deuterated MSG in vitro was developed to protonate the amides deeply
      buried in the protein core. Of interest, during the course of the assignment, an
      isoaspartyl linkage in the protein sequence was unambiguously identified.
      Chemical shift assignments of this system are a first step in the study of how
      the domains of the protein change in response to ligand binding and for
      characterizing the dynamical properties of the enzyme that are likely important
      for function.

PMID- 12188668
TI  - Synthesis of 5-fluoro N-acetylglucosamine glycosides and pyrophosphates via
      epoxide fluoridolysis: versatile reagents for the study of glycoconjugate
      biochemistry.
AB  - Numerous carbohydrate-processing enzymes facilitate catalysis via stabilization
      of positive charges on or near the C-1, C-4, C-5, or C-6 positions. Substrate
      analogues differing only in the substitution of a fluorine for the axial C-5
      hydrogen would possess reduced electron density at these positions and could be
      useful mechanistic probes of these enzymes. Introduction of this 5-fluoro
      substituent after radical halogenation was problematic because of the
      incompatibility of many protecting groups to the radical halogenation and the
      instability of the subsequent 5-fluoro hexosamines. Thus, to allow easy access to
      a wide variety of 5-fluoro glycosides and glycosyl phosphates, a versatile method
      for the introduction of the 5-fluoro group has been developed, the key step being
      the fluoridolysis of C-5, 6 epoxides. By use of this method, two fluorinated
      carbohydrates, uridine 5'-diphospho-5-fluoro-N-acetylglucosamine and octyl 5
      fluoro-N-acetylglucosamine, have been synthesized. Initial biochemical
      investigations of these compounds show that 5-fluoro analogues are useful probes
      of transition-state charge development in several enzyme-catalyzed reactions.

PMID- 12188669
TI  - Singlet-triplet gap in triplet ground-state biradicals is modulated by
      substituent effects.
AB  - Three S = 1 bis(semiquinone) complexes have been prepared. To ensure
      ferromagnetic intramolecular exchange coupling, the two semiquinones are attached
      1,3 to a 5-substituted phenylene ring. The biradical complexes differ in their
      meta-substituents: 1-NMe(2)(), X = N,N-dimethylamino; 1-t-Bu, X = tert-butyl; 1
      NO(2)(), X = nitro. All three structures have been determined by X-ray
      crystallography. Results of structural studies indicate that the biradical
      ligands of all three complexes have nearly identical conformations with average
      semiquinone ring torsions of 32 degrees +/- 2 degrees relative to the 5
      substituted phenylene ring. The exchange parameter, J (Eta = -2JS(1).S(2)),
      ranges from +31.0 +/- 0.6 cm(-)(1) for 1-NO(2)() to +59.3 +/- 1.2 cm(-)(1) for 1
      t-Bu, with J = +34.9 +/- 0.7 cm(-)(1) for 1-NMe(2)(). Since the conformations are
      nearly identical, the differences in exchange coupling parameter J are due to
      substituent effects. The experimental results are supported by Huckel theory
      arguments and previous computational work.

PMID- 12188670
TI  - Nucleophilically assisted and cationic ring-opening polymerization of tin-bridged
      [1]ferrocenophanes.
AB  - To obtain mechanistic insight, detailed studies of the intriguing "spontaneous"
      ambient temperature ring-opening polymerization (ROP) of tin-bridged
      [1]ferrocenophanes Fe(eta-C(5)H(4))(2)SnR(2) 3a (R = t-Bu) and 3b (R = Mes) in
      solution have been performed. The investigations explored the influence of non
      nucleophilic additives such as radicals and radical traps, neutral and anionic
      nucleophiles, Lewis acids, protic species, and other cationic electrophiles.
      Significantly, two novel methodologies and mechanisms for the ROP of strained
      [1]ferrocenophanes are proposed based on this study. First, as the addition of
      amine nucleophiles such as pyridine was found to strongly accelerate the
      polymerization rate in solution, a new nucleophilicallyassisted ROP methodology
      was proposed. This operates at ambient temperature in solution even in the
      presence of chlorosilanes but, unlike the anionic polymerization of
      ferrocenophanes, does not involve cyclopentadienyl anions. Second, the addition
      of small quantities of the electrophilic species H(+) and Bu(3)Sn(+) was found to
      lead to a cationic ROP process. These studies suggest that the "spontaneous" ROP
      of tin-bridged [1]ferrocenophanes may be a consequence of the presence of
      spurious, trace quantities of Lewis basic or acidic impurities. The new ROP
      mechanisms reported are likely to be of general significance for the ROP of other
      metallocenophanes (e.g., for thermal ROP in the melt) and for other metallacycles
      containing group 14 elements.

PMID- 12188671
TI  - Enantiomeric and enantiotopic analysis of cone-shaped compounds with C(3) and
      C(3)(v) symmetry using NMR spectroscopy in chiral anisotropic solvents.
AB  - We describe the enantiomeric and enantiotopic analysis of the NMR spectra of
      compounds derived from the functionalized cone-shaped core, cyclotriveratrylenes
      (CTV), dissolved in weakly oriented lyotropic chiral liquid crystals (CLCs) based
      on organic solutions of poly-gamma-benzyl-L-glutamate. The CTV core lacks
      prostereogenic as well as stereogenic tetrahedral centers. However, depending on
      the pattern of substitution, chiral and achiral compounds with different
      symmetries can be obtained. Thus, symmetrically nonasubstituted CTVs (C(3)
      symmetry) are optically active and exhibit enantiomeric isomers, while
      symmetrically hexasubstituted (C(3v) symmetry) derivatives are prochiral and
      possess enantiotopic elements. In the first part we use (2)H and (13)C NMR to
      study two nonasubstituted (-OH or -OCH(3)) CTVs, where the ring methylenes are
      fully deuterated, and show for the first time that the observation of
      enantiomeric discrimination of chiral molecules with a 3-fold symmetry axis is
      possible in a CLC. It is argued that this discrimination reflects different
      orientational ordering of the M and P isomers, rather than specific chiral short
      range solvent-solute interactions that may affect differently the magnetic
      parameters of the enantiomers or even their geometry. In the second part we
      present similar measurements on hexasubstituted CTV with flexible side groups (
      OC(O)CH(3) and the, partially deuterated bidentate, -OCH(2)CH(2)O-), having on
      the average C(3v) symmetry. No spectral discrimination of enantiotopic sites was
      detected for the -OC(O)CH(3) derivative. This is consistent with a recent
      theoretical work (J. Chem. Phys. 1999, 111, 6890) that indicates that in C(3v)
      molecules no chiral discrimination between enantiotopic elements, based on
      ordering, is possible. In contrast, a clear splitting was observed in the (2)H
      spectra of the enantiotopic deuterons of the side groups in the
      tri(dioxyethylene)-CTV. It is argued that this discrimination reflects different
      ordering characteristics of the various, rapidly (on the NMR time scale)
      interconverting conformers of this compound. Assuming two twisted structures for
      each of the dioxyethylene side groups, four different conformers are expected,
      comprising two sets of enantiomeric pairs with, respectively, C(3) and C(1)
      symmetries. Differential ordering and/or fractional population imbalance of these
      enantiomeric pairs leads to the observed spectral discrimination of sites in the
      side chains that on average form enantiotopic pairs.

PMID- 12188672
TI  - Supramolecular assembly at interfaces: formation of an extended two-dimensional
      coordinate covalent square grid network at the air-water interface.
AB  - Reaction of a Langmuir monolayer of an amphiphilic pentacyanoferrate(3+) complex
      with Ni(2+) ions from the subphase results in the formation of a two-dimensional
      iron-nickel cyanide-bridged network at the air-water interface. The network can
      be transferred to various supports to form monolayer or multilayer lamellar films
      by the Langmuir-Blodgett (LB) technique. The same network does not form from
      homogeneous reaction conditions. Therefore, the results demonstrate the potential
      utility of an interface as a structure director in the assembly of low
      dimensional coordinate covalent network solids. Characterization of the LB film
      extended networks by X-ray photoelectron spectroscopy (XPS), FT-IR spectroscopy,
      SQUID magnetometry, X-ray absorption fine structure (XAFS), and grazing incidence
      synchrotron X-ray diffraction (GIXD) revealed a face-centered square grid
      structure with an average domain size of 3600 A(2). Magnetic measurements
      indicated that the network undergoes a transition to a ferromagnetic state below
      a T(c) of 8 K.

PMID- 12188673
TI  - Asymmetric cyclopentannelation: camphor-derived auxiliary.
AB  - The scope of an enantioselective cyclopentannelation reaction that makes use of
      allenyl ether-derived nucleophiles has been probed. The enantioselectivity is
      induced by a traceless chiral auxiliary that is easily derived from camphor. It
      has been shown that for gamma-substituted allene ethers that are axially chiral,
      very high enantiomeric excesses of cyclopentenone products are observed in the
      matched cases. Two fundamentally different mechanisms are observed, one for the
      cyclizations of allenyl ketones (see eq 7), the other for the cyclizations of
      allenyl alcohols (see eq 11). The methodology is versatile, efficient, and well
      suited for applications in synthesis.

PMID- 12188674
TI  - Oxidative cyclization based on reversing the polarity of enol ethers and ketene
      dithioacetals. Construction of a tetrahydrofuran ring and application to the
      synthesis of (+)-nemorensic Acid.
AB  - The utility of oxidative cyclization reactions for the construction of
      tetrahydrofuran rings has been examined. In these experiments, alcohol
      nucleophiles were found to be effective traps for radical cation intermediates
      generated from both enol ether and ketene dithioacetal groups. The reactivity of
      the alcohol trapping group appeared to lie between that of an enol ether and an
      allylsilane trapping group. The stereochemical outcome of cyclization reactions
      originating from the oxidation of an enol ether was found to be controlled by
      stereoelectronic factors. The utility of these cyclization reactions was
      illustrated with the synthesis of a key tetrahydrofuran building block for the
      synthesis of linalool oxide and rotundisine. Cyclization reactions triggered by
      the oxidation of a ketene dithioacetal led to far greater levels of
      stereoselectivity. The stereochemical outcome of these reactions was shown to
      arise from steric factors involving the larger ketene acetal group. The synthetic
      utility of cyclizations utilizing ketene dithioacetal derived radical cations was
      demonstrated by completing an asymmetric synthesis of (+)-nemorensic acid.
      Finally, the reactions were shown to be compatible with the use of an amide
      nucleophile and the direct formation of a lactone product.

PMID- 12188676
TI  - Comparative IR study of nitric oxide reactions with sublimed layers of iron(II)-
      and ruthenium(II)-meso-tetraphenylporphyrinates.
AB  - The interactions of nitric oxide gas with thin layers of Fe(II)(TPP) and
      Ru(II)(TPP), obtained by sublimation onto low-temperature substrate (77 K), has
      been investigated by means of IR spectroscopy (TPP = meso
      tetraphenylporphyrinate). Only simple addition of NO to form Fe(TPP)(NO) is
      observed for the iron-porphyrin Fe(II)(TPP), while, in contrast, Ru(II)(TPP)
      promotes NO disproportionation to form the nitrosyl-nitrito complex
      Ru(TPP)(NO)(ONO) and N(2)O. Thin layers of Fe(TPP)(NO) are inert to further
      reaction with excess NO; however, the nitrosyl-nitro complex Fe(TPP)(NO)(NO(2))
      is readily formed when traces of dioxygen are added to the NO atmosphere. When
      the NO(2) concentrations in the NO/NO(2) mixture are relatively high, the nitrato
      complex Fe(TPP)(NO(3)) is also formed. Spectral data are given indicating that
      moderate shifts in the nitrosyl stretching frequency of Fe(TPP)(NO) are due to
      crystal packing effects, rather than to the H-bonding of coordinated NO with
      protic contaminants suggested in an earlier publication. Removal of NO by
      exhaustive evacuation from layers containing Fe(TPP)(NO)(NO(2)) leads to
      formation of Fe(TPP)(NO) and Fe(TPP)(NO(3)).

PMID- 12188675
TI  - Hydrocarbon oxidation by Bis-mu-oxo manganese dimers: electron transfer, hydride
      transfer, and hydrogen atom transfer mechanisms.
AB  - Described here are oxidations of alkylaromatic compounds by dimanganese mu-oxo
      and mu-hydroxo dimers [(phen)(2)Mn(IV)(mu-O)(2)Mn(IV)(phen)(2)](4+)
      ([Mn(2)(O)(2)](4+)), [(phen)(2)Mn(IV)(mu-O)(2)Mn(III)(phen)(2)](3+)
      ([Mn(2)(O)(2)](3+)), and [(phen)(2)Mn(III)(mu-O)(mu-OH)Mn(III)(phen)(2)](3+)
      ([Mn(2)(O)(OH)](3+)). Dihydroanthracene, xanthene, and fluorene are oxidized by
      [Mn(2)(O)(2)](3+) to give anthracene, bixanthenyl, and bifluorenyl, respectively.
      The manganese product is the bis(hydroxide) dimer, [(phen)(2)Mn(III)(mu
      OH)(2)Mn(II)(phen)(2)](3+) ([Mn(2)(OH)(2)](3+)). Global analysis of the UV/vis
      spectral kinetic data shows a consecutive reaction with buildup and decay of
      [Mn(2)(O)(OH)](3+) as an intermediate. The kinetics and products indicate a
      mechanism of hydrogen atom transfers from the substrates to oxo groups of
      [Mn(2)(O)(2)](3+) and [Mn(2)(O)(OH)](3+). [Mn(2)(O)(2)](4+) is a much stronger
      oxidant, converting toluene to tolyl-phenylmethanes and naphthalene to
      binaphthyl. Kinetic and mechanistic data indicate a mechanism of initial
      preequilibrium electron transfer for p-methoxytoluene and naphthalenes because,
      for instance, the reactions are inhibited by addition of [Mn(2)(O)(2)](3+). The
      oxidation of toluene by [Mn(2)(O)(2)](4+), however, is not inhibited by
      [Mn(2)(O)(2)](3+). Oxidation of a mixture of C(6)H(5)CH(3) and C(6)H(5)CD(3)
      shows a kinetic isotope effect of 4.3 +/- 0.8, consistent with C-H bond cleavage
      in the rate-determining step. The data indicate a mechanism of initial hydride
      transfer from toluene to [Mn(2)(O)(2)](4+). Thus, oxidations by manganese oxo
      dimers occur by three different mechanisms: hydrogen atom transfer, electron
      transfer, and hydride transfer. The thermodynamics of e(-), H(*), and H(-)
      transfers have been determined from redox potential and pK(a) measurements. For a
      particular oxidant and a particular substrate, the choice of mechanism is
      influenced both by the thermochemistry and by the intrinsic barriers. Rate
      constants for hydrogen atom abstraction by [Mn(2)(O)(2)](3+) and
      [Mn(2)(O)(OH)](3+) are consistent with their 79 and 75 kcal mol(-)(1) affinities
      for H(*). In the oxidation of p-methoxytoluene by [Mn(2)(O)(2)](4+), hydride
      transfer is thermochemically 24 kcal mol(-)(1) more facile than electron
      transfer; yet the latter mechanism is preferred. Thus, electron transfer has a
      substantially smaller intrinsic barrier than does hydride transfer in this
      system.

PMID- 12188677
TI  - Computational study of the influence of solvent on (16)O/(18)O equilibrium
      isotope effects in phosphate deprotonation reactions.
AB  - Results from theoretical calculations of (16)O/(18)O equilibrium isotope effects
      (EIEs) on deprotonation of phosphate and methyl phosphate monoanions as well as
      their deuterated counterparts are reported. The EIEs are calculated from the
      Bigeleisen equation using harmonic vibrational frequencies from several quantum
      mechanical methods (HF, DFT, MP2, and AM1). All methods correctly predict the
      qualitative trends in the EIEs related to the different isotope substitutions.
      However, the calculated gas-phase values are found to be systematically higher
      than those experimentally observed in aqueous solution. On the other hand, the
      addition of explicit solvent molecules (up to 24 waters) in the first solvation
      shells of the phosphate ion substantially improves the calculated EIE, which
      approaches the experimental value with increasing size of the water cluster. The
      large effects of surrounding water molecules on the phosphate deprotonation EIE
      can be explained by the strong solute-solvent interactions, which result in
      solvent coupled vibrational modes of the phosphate ions.

PMID- 12188679
TI  - Ammoniated alkali fullerides (ND(3))(x)NaA(2)C(60): ammonia specific effects and
      superconductivity.
AB  - The crystal structure of the superconducting (ND(3))(x)()NaA(2)C(60) (0.7 < or =
      x < or = 1, A= K, Rb) fullerides (T(c)= 6-15 K) has been studied by synchrotron X
      ray and neutron powder diffraction. It is face-centered cubic (fcc) to low
      temperatures with Na(+)-ND(3) pairs residing in the octahedral interstices. These
      are disordered over the corners of two "interpenetrating" cubes with the Na(+)
      ions and the N atoms displaced by approximately 2.0 A and approximately 0.5 A
      from the center of the site and statically disordered over the corners of the
      inner and outer cube, respectively. Close contacts between the D atoms of the
      ND(3) molecules and electron rich 6:6 C-C bonds of neighboring C(60) units
      provide the signature of weak N-D.pi hydrogen-bonding interactions, which control
      the intermolecular packing in the crystal and may determine the unusual
      superconducting properties.

PMID- 12188678
TI  - An alternative synthetic route of [3(5)](1,2,3,4,5)cyclophane, and structural
      properties of multibridged [3(n)]cyclophanes and their charge-transfer complexes
      in the solid state.
AB  - To develop an improved synthetic route to [3(6)](1,2,3,4,5,6)cyclophane (CP) 2, a
      more practical synthetic route to [3(5)](1,2,3,4,5)CP 3 than the original one was
      developed, which started from [3(2)](1,3)CP 7 via [3(4)](1,2,4,5)CP 5. The
      fundamental structural parameters of [3(n)]CPs (n = 3-6) in the solid state were
      elucidated, and the observed structures were in good agreement with the most
      stable conformers in solution and those predicted by the theoretical
      calculations. In the case of [3(6)]CP 2, the most stable C(6)(h) structure was
      observed in the crystal structure of the 2-TCNQ-F(4) (1:1) complex, whereas the
      highly strained structure with a D(6)(h) symmetry was observed in the crystal
      structure of 2 and the 2:TCNQ:benzene (1:1:1) complex because of a severe
      disorder problem. [3(n)]CPs (n > 3) showed reversible redox processes, and 2
      (+0.39 V vs F(c)/F(c)(+), Cl(2)CHCHCl(2)) showed the lowest first half-wave
      oxidation potential [E(1/2) (I)] in [3(n)]CPs. The E(1/2) (I) data support the
      strong donating ability of 2 and its lower homologues. This is attributed to
      their molecular structures where effective hyperconjugation between the benzyl
      hydrogens and benzene ring is possible. By taking advantage of the strong
      electron-donating ability of [3(n)]CPs, their CT complexes with TCNE, TCNQ, and
      TCNQ-F(4) were prepared, and their crystal structural properties were examined.
      The single-crystal conductivity data of the CT complexes indicated that the TCNQ
      F(4) complexes showed higher conductivities than the corresponding TCNQ complexes
      mainly due to a larger charge separation. Among the [3(n)]CP-TCNQ complexes, the
      [3(3)](1,3,5)CP 6-TCNQ-F(4) (1:1) complex showed the highest conductivity (10(
      )(4) S cm(-)(1)), and this was ascribed to the formation of an infinite column of
      partially overlapped acceptors with a short acceptor-acceptor distance, while the
      formation of such a column was not observed in the 2-TCNQ-F(4) complex. Although
      the conductivities of the cyclophane-CT complexes are much lower than those of
      the TTF related complexes, this study successfully provides the basic knowledge
      for understanding the CT interactions in the solid state.

PMID- 12188680
TI  - Structure of V(2)O(5)*nH(2)O xerogel solved by the atomic pair distribution
      function technique.
AB  - A long-standing issue regarding the local and long-range structure of
      V(2)O(5)*nH(2)O xerogel has been successfully addressed. The full three
      dimensional structure of the lamellar turbostratic V(2)O(5)*nH(2)O xerogel was
      determined by the atomic pair distribution function technique. We show that on
      the atomic scale the slabs of the xerogel can be described well as almost perfect
      pairs (i.e., bilayers) of single V(2)O(5) layers made of square pyramidal VO(5)
      units. These slabs are separated by water molecules and stack along the z-axis of
      a monoclinic unit cell (space group C2/m) with parameters a = 11.722(3) A, b =
      3.570(3) A, c = 11.520(3) A, and beta = 88.65 degrees. The stacking sequence
      shows signatures of turbostratic disorder and a structural coherence limited to
      50 A.

PMID- 12188681
TI  - Electron affinity of the guanine-cytosine base pair and structural perturbations
      upon anion formation.
AB  - The adiabatic electron affinity (AEA) for the Watson-Crick guanine-cytosine (GC)
      DNA base pair is predicted using a range of density functional methods with
      double- and triple-zeta plus polarization plus diffuse (DZP++ and TZ2P++) basis
      sets in an effort to bracket the true electron affinity. The methods used have
      been calibrated against a comprehensive tabulation of experimental electron
      affinities (Chem.Rev. 2002, 102, 231). Optimized structures for GC and the GC
      anion are compared to the neutral and anionic forms of the individual bases as
      well as Rich's 1976 X-ray structure for sodium guanylyl-3',5'-cytidine
      nonahydrate, GpC.9H(2)O. Structural distortions and natural population (NPA)
      charge distributions of the GC anion indicate that the unpaired electron is
      localized primarily on the cytosine moiety. Unlike treatments using second-order
      perturbation theory (MP2), density functional theory consistently predicts a
      substantial positive adiabatic electron affinity for the GC pair (e.g.,
      TZ2P++/B3LYP: +0.48 eV). The stabilization of C(-) via three hydrogen bonds to
      guanine is sufficient to facilitate adiabatic binding of an electron to GC and is
      also consistent with the positive experimental electron affinities obtained by
      photoelectron spectroscopy of cytosine anions incrementally microsolvated with
      water molecules. The pairing (dissociation) energy for GC(-) (35.6 kcal/mol) is
      determined with inclusion of electron correlation and shows the anion to have
      greater thermodynamic stability; the pairing energy for neutral GC (TZ2P++/B3LYP
      23.9 kcal/mol) compares favorably to previous MP2/6-31G (23.4 kcal/mol) results
      and a debated experiment (21.0 kcal/mol).

PMID- 12188682
TI  - Use of U-shaped donor-bridge-acceptor molecules to study electron tunneling
      through nonbonded contacts.
AB  - A systematic determination of electronic coupling matrix elements in U-shaped
      molecules is demonstrated. The unique architecture of these systems allows for
      the determination of the electronic coupling through a pendant molecular moiety
      that resides between the donor and acceptor groups; this moiety quantifies the
      efficiency of electron tunneling through nonbonded contacts. Experimental
      electron-transfer rate constants and reaction free energies are used to calibrate
      a molecular-based model that describes the solvation energy. This approach makes
      it possible to experimentally determine electronic couplings and compare them
      with computational values.

PMID- 12188683
TI  - Probing the electronic structure of [MoOS(4)](-) centers using anionic
      photoelectron spectroscopy.
AB  - Using photodetachment photoelectron spectroscopy (PES) in the gas phase, we
      investigated the electronic structure and chemical bonding of six anionic
      [Mo(V)O](3+) complexes, [MoOX(4)](-) (where X = Cl (1), SPh (2), and SPh-p-Cl
      (3)), [MoO(edt)(2)](-) (4), [MoO(bdt)(2)](-) (5), and [MoO(bdtCl(2))(2)](-) (6)
      (where edt = ethane-1,2-dithiolate, bdt = benzene-1,2-dithiolate, and bdtCl(2) =
      3,6-dichlorobenzene-1,2-dithiolate). The gas-phase PES data revealed a wealth of
      new electronic structure information about the [Mo(V)O](3+) complexes. The energy
      separations between the highest occupied molecular orbital (HOMO) and HOMO-1 were
      observed to be dependent on the O-Mo-S-C(alpha) dihedral angles and ligand types,
      being relatively large for the monodentate ligands, 1.32 eV for Cl and 0.78 eV
      for SPh and SPhCl, compared to those of the bidentate dithiolate complexes, 0.47
      eV for edt and 0.44 eV for bdt and bdtCl(2). The threshold PES feature in all six
      species is shown to have the same origin and is due to detaching the single
      unpaired electron in the HOMO, mainly of Mo 4d character. This result is
      consistent with previous theoretical calculations and is verified by comparison
      with the PES spectra of two d(0) complexes, [VO(bdt)(2)](-) and
      [VO(bdtCl(2))(2)](-). The observed PES features are interpreted on the basis of
      theoretical calculations and previous spectroscopic studies in the condensed
      phase.

PMID- 12188684
TI  - Mineralization of single flexible polyelectrolyte molecules.
AB  - Conformation of a single flexible polyelectrolyte molecule with a hydrophobic
      backbone in aqueous solution is effected by the interplay of the short-range
      intramolecular attraction and the long-range Coulomb repulsion. The conformation
      can be frozen if the molecule is trapped by a solid substrate. With this
      approach, we prepared the range of single molecule templates from poly(2
      vinylpyridine) (P2VP) deposited on the surface of Si-wafer or mica in different
      conformations from an elongated wormlike coil to compact globule. Pd(+2) was
      coordinated by P2VP via an ion exchange reaction exposing the samples to
      palladium acetate acidic aqueous solution. In the next step, Pd(+2) was reduced
      by dimethylamine borane. This route results in wire-shaped metallic nanoparticle
      assembles of about 2-5 nm in diameter and 50-700 nm in length. The conformation
      and size of the underlaying polyelectrolyte molecules determine the dimensions of
      nanoparticles.

PMID- 12188685
TI  - Computational insights on the challenges for polymerizing polar monomers.
AB  - Taking Pd di-imine catalysts as an example, we use first principles density
      functional theory (B3LYP/6-31G) to investigate the chain propagation steps for
      polymerization of polar monomers. We start with the complex formed from insertion
      of ethylene into the polymer chain and consider insertion into the Pd-C bond for
      each of four polar monomers: methyl acrylate, vinyl acetate, vinyl chloride, and
      acrylonitrile. We find 2,1-insertion is favored in each case (by 3 to 5
      kcal/mol), resulting in a product with a strong interaction of the polar group
      for the growing polymer chain with the metal. Next, we insert another unit of the
      same polar monomer or an ethylene unit (except for acrylonitrile). We optimize
      the structures for all important intermediates and transition states using a
      continuum dielectric to account for solvation effects. These studies pinpoint the
      critical difficulties in designing catalysts to polymerize polar monomers.

PMID- 12188686
TI  - Photofragment translational spectroscopy of 1,3-butadiene and 1,3-butadiene
      1,1,4,4-d(4) at 193 nm.
AB  - The photodissociation dynamics of 1,3-butadiene at 193 nm have been investigated
      with photofragment translational spectroscopy coupled with product
      photoionization using tunable VUV synchrotron radiation. Five product channels
      are evident from this study: C(4)H(5) + H, C(3)H(3) + CH(3), C(2)H(3) + C(2)H(3),
      C(4)H(4) + H(2), and C(2)H(4) + C(2)H(2). The translational energy (P(E(T)))
      distributions suggest that these channels result from internal conversion to the
      ground electronic state followed by dissociation. To investigate the dissociation
      dynamics in more detail, further studies were carried out using 1,3-butadiene
      1,1,4,4-d(4). Branching ratios were determined for the channels listed above, as
      well as relative branching ratios for the isotopomeric species produced from 1,3
      butadiene-1,1,4,4-d(4) dissociation. C(3)H(3) + CH(3) is found to be the dominant
      channel, followed by C(4)H(5) + H and C(2)H(4) + C(2)H(2), for which the yields
      are approximately equal. The dominance of the C(3)H(3) + CH(3) channel shows that
      isomerization to 1,2-butadiene followed by dissociation is facile.

PMID- 12188687
TI  - Density functional study of the mechanism of a tyrosine phosphatase: I.
      Intermediate formation.
AB  - The first step in the catalytic mechanism of a protein tyrosine phosphatase, the
      transfer of a phosphate group from the phosphotyrosine substrate to a cysteine
      side chain of the protein to form a phosphoenzyme intermediate, has been studied
      by combining density functional calculations of an active-site cluster with
      continuum electrostatic descriptions of the solvent and the remainder of the
      protein. This approach provides the high level of quantum chemical methodology
      needed to adequately model phosphotransfer reactions with a reasonable
      description of the environment around the active site. Energy barriers and
      geometries along a reaction pathway are calculated. In the literature, mechanisms
      assuming both a monoanionic and a dianionic substrate have been proposed; this
      disagreement is addressed by performing calculations for both possibilities. For
      the dianionic substrate, a dissociative reaction pathway with early proton
      transfer to the leaving group and a 9 kcal/mol energy barrier is predicted (the
      experimental estimate is ca. 14 kcal/mol), while for the monoanionic substrate,
      an associative pathway with late proton transfer and a 22 kcal/mol energy barrier
      is predicted. These results, together with a review of experimental evidence,
      support the dianionic-substrate/dissociative-pathway alternative. The
      relationship between a dianionic or monoanionic substrate and a dissociative or
      associative pathway, respectively, can be understood in terms of classical
      organic chemical reaction pathways.

PMID- 12188690
TI  - Two reaction zones in a competing reactions system with initially separated
      components.
AB  - The long-time properties of a system with initially separated components and two
      competing reactions, reversible A1+B<-->C1 and irreversible A2+B-->C2, are
      studied. It is assumed that the backward constant g(1) of the reversible reaction
      A1+B<-->C1 is small. The dynamics of the system is described by means of a
      crossover from an "irreversible" regime (for times t<<g(-1)(1)) to a "reversible"
      regime (for times t>>g(-1)(1)). It is shown that in contrast to the
      "irreversible" regime, where both reactions occur in one reaction zone, the
      "reversible" regime is characterized by two distinctive reaction zones. These are
      the A1+B<-->C1 reversible reaction zone and the A2+C1-->A1+C2 irreversible
      reaction zone. Numerical computations of the mean-field kinetic equations confirm
      these asymptotic results.

PMID- 12188688
TI  - Conformational preferences of jet-cooled melatonin: probing trans- and cis-amide
      regions of the potential energy surface.
AB  - The hormone melatonin (N-acetyl-5-methoxytryptamine) is an indole derivative with
      a flexible peptide-like side chain attached at the C3 position. Using a
      combination of two-color resonant two-photon ionization (2C-R2PI), laser-induced
      fluorescence excitation (LIF), resonant ion-dip infrared spectroscopy (RIDIRS),
      fluorescence-dip infrared spectroscopy (FDIRS), and UV-UV hole-burning
      spectroscopy, the conformational preferences of melatonin in a molecular beam
      have been determined. Three major trans-amide conformers and two minor cis-amide
      conformers have been identified in the R2PI spectrum and characterized with
      RIDIRS and FDIRS. Structural assignments are made using the infrared spectra in
      concert with density functional theory and localized MP2 calculations.
      Observation of cis-amide melatonin conformers in the molecular beam, despite the
      large energy gap (approximately 3 kcal/mol) between trans- and cis-amides, is
      striking because there are at least nine lower-energy trans-amide minima that are
      not detected. The implications of this observation for cooling and trapping
      conformational population in a supersonic expansion are discussed.

PMID- 12188691
TI  - Lyapunov exponent pairing for a thermostatted hard-sphere gas under shear in the
      thermodynamic limit.
AB  - We demonstrate why for a sheared gas of hard spheres, described by the SLLOD
      equations with an isokinetic Gaussian thermostat in between collisions,
      deviations of the conjugate pairing rule for the Lyapunov spectrum are to be
      expected, employing a previous result that for a large number of particles N, the
      isokinetic Gaussian thermostat is equivalent to a constant friction thermostat,
      up to 1/sqrt[N] fluctuations. We also show that these deviations are at most of
      the order of the fourth power in the shear rate.

PMID- 12188692
TI  - Time and length scales for diffusion in liquids.
AB  - The first six even moments of the displacement of a molecule in water and an atom
      in liquid argon are found by molecular dynamics simulations and compared with the
      moments predicted by diffusion theory. We find a noticeable difference between
      the moments higher than the second. The ratio between predicted and calculated
      moments approaches unity as 1/t for times larger than 10 ps. Continuous time
      random walk is used to explain this slow approach of the moments to their
      diffusion limit.

PMID- 12188693
TI  - Scaling behavior of the surface in ballistic deposition.
AB  - Using a dynamical scaling form for the surface fractal dimension as well as
      efficient algorithms for the simulation and analysis of the surface in three
      dimensional ballistic deposition, we show that while the top of the surface is
      self-affine, the complete surface including overhangs has fractal dimension D(f)
      approximately 3. The existence of such a fractal surface is a consequence of the
      difficulty of closing off voids in three and higher dimensions. By studying a
      modified ballistic deposition model in which sticking is allowed with a given
      probability p, we show that the surface undergoes a phase transition from fractal
      to compact at a finite value of p. Our results also have implications for
      understanding the surface morphology in sedimentary rocks and low-temperature
      thin films.

PMID- 12188694
TI  - Effect of director distortions on morphologies of phase separation in liquid
      crystals.
AB  - We study phase separation from a nematic liquid crystal with spatially nonuniform
      director gradients. Particles of a phase-separated component, which is either an
      isotropic fluid (silicone oil) or a nonmesogenic photopolymer, accumulate in the
      regions with the strongest director distortions, thus reducing the overall energy
      of the system.

PMID- 12188695
TI  - Interaction potential between two spheres mediated by excluded volume polymers.
AB  - The interaction between two spheres in a solution of nonadsorbing polymers, with
      excluded volume interaction, is calculated from the depletion layers around the
      spheres using the generalized Gibbs adsorption equation. By combining the bulk
      correlation length with the curvature-dependent interfacial tension between a
      sphere and the surrounding polymer solution [Hanke, Eisenriegler, and Dietrich,
      Phys. Rev. E 59, 6853 (1999)], the depletion layer thickness around a sphere is
      obtained. The resulting contact potential agrees with a scaling prediction of de
      Gennes in the semidilute regime.

PMID- 12188696
TI  - Physics of psychophysics: Stevens and Weber-Fechner laws are transfer functions
      of excitable media.
AB  - Sensory arrays made of coupled excitable elements can improve both their input
      sensitivity and dynamic range due to collective nonlinear wave properties. This
      mechanism is studied in a neural network of electrically coupled (e.g., via gap
      junctions) elements subject to a Poisson signal process. The network response
      interpolates between a Weber-Fechner logarithmic law, and a Stevens power law
      depending on the relative refractory period of the cell. Therefore, these
      nonlinear transformations of the input level could be performed in the sensory
      periphery simply due to a basic property: the transfer function of excitable
      media.

PMID- 12188697
TI  - Stochastic resonance for motion of flexible macromolecules in solution.
AB  - We consider a dilute or semidilute polymer solution with localized attracting
      centers near a flat phase boundary and assume it driven by both stochastic and
      periodic forces. The attracting inhomogeneities restrict the free motion of
      macromolecules and play the role of fixed pinning centers. The flat boundary is
      modeled by a bistable potential whose minima attract the movable polymer segments
      between neighboring pinning points. We study the motion of these segments. The
      stochastic forces lead to stochastic oscillations of the polymer parts between
      the two potential wells near the phase boundary. Application of a small temporal
      periodic force can synchronize these oscillations and leads to the phenomenon of
      stochastic resonance for a nonvanishing noise intensity. As an outcome of our
      theory in agreement with numerical simulations, the resonance is stronger for
      wider and/or less deep potentials and observed at smaller values of the noise
      intensity. Additionally, we discuss under what conditions doubly stochastic
      resonance of the macromolecular motion occurs, that is, if bistability of the
      potential near the boundary originates in the action of multiplicative noise.

PMID- 12188698
TI  - Generalized Langevin equation approach to higher-order classical response: second
      order-response time-resolved Raman experiment in CS2.
AB  - A simple, systematic generalized Langevin equation approach for calculating
      classical nonlinear response functions is formulated and discussed. The two-time
      Poisson brackets appearing at second and higher order are rendered tractable by a
      physically motivated approximation. The method is used to calculate the fifth
      order (second order response) Raman response of liquid CS2. Agreement with
      simulation is good, but the simplicity of the theoretical expression suggests
      that the path to obtaining qualitatively new information about liquids with the
      fifth order experiment is uncertain. Further applications of the basic approach
      are suggested.

PMID- 12188699
TI  - Tightness of slip-linked polymer chains.
AB  - We study the interplay between entropy and topological constraints for a polymer
      chain in which sliding rings (slip links) enforce pair contacts between monomers.
      These slip links divide a closed ring polymer into a number of subloops which can
      exchange length among each other. In the ideal chain limit, we find the joint
      probability density function for the sizes of segments within such a slip-linked
      polymer chain (paraknot). A particular segment is tight (small in size) or loose
      (of the order of the overall size of the paraknot) depending on both the number
      of slip links it incorporates and its competition with other segments. When self
      avoiding interactions are included, scaling arguments can be used to predict the
      statistics of segment sizes for certain paraknot configurations.

PMID- 12188701
TI  - Up and down cascades: three-dimensional magnetic field model.
AB  - In our previous works we already have proposed a two-dimensional model of
      geodynamo. Now we use the same approach to build a three-dimensional self-excited
      geodynamo model that generates a large scale magnetic field from whatever small
      initial field, using the up and down cascade effects of a multiscale turbulent
      system of cyclones. The multiscale system of turbulent cyclones evolves in six
      domains of an equatorial cylindrical layer of the core. The appearance of new
      cyclones is realized by two cascades: a turbulent direct cascade and an inverse
      cascade of coupling of similar cyclones. The interaction between the different
      domains is effected through a direct cascade parameter which is essential for the
      statistics of the long-life symmetry breaking. Generation of the secondary
      magnetic field results from the interaction of the components of the primary
      magnetic field with the turbulent cyclones. The amplification of the magnetic
      field is due to the transfer of energy from the turbulent helical motion to the
      generated magnetic field. The model demonstrates a phase transition through the
      parameter characterizing this energy transfer. In the supercritical domain we
      obtain long-term intervals of constant polarity (chrons) and quick reversals;
      relevant time constants agree with paleomagnetic observations. Possible
      application of the model to the study of the geometrical structure of the
      geomagnetic field (and briefly other planetary fields) is discussed.

PMID- 12188700
TI  - Half-width of intensity profiles of light scattered from self-affine fractal
      random surfaces and simulational verifications.
AB  - Based on the fact that the half-width of the Fourier transform is inversely
      proportional to that of a symmetrical primary decay function, the half-width of
      the intensity profiles of light scattered from self-affine fractal random
      surfaces in the whole k( perpendicular ) region is studied. The primary function,
      whose Fourier transform is the intensity profile, is approximated with a simple
      mathematical decay function by equating their half-widths and maximums. The
      expression obtained for the half-width of the scattered intensity profiles
      reduces to the present results in the two extreme cases with the scattering
      roughness factors being either very small or very large. For a complete
      verification, we perform a simulation of the light scattering, in which self
      affine fractal random surfaces are generated with an algorithm that is an analogy
      to the formation of laser speckles. The simulated and theoretical results conform
      well.

PMID- 12188702
TI  - Excitation of rotational modes in two-dimensional systems of driven Brownian
      particles.
AB  - Models of active Brownian motion in two-dimensional (2D) systems developed
      earlier are investigated with respect to the influence of linear attracting
      forces and external noise. Our consideration is restricted to the case that the
      driving is rather weak and that the forces show only weak deviations from radial
      symmetry. In this case an analytical study of the bifurcations of the system is
      possible. We show that in the presence of external linear forces with only small
      deviations from radial symmetry, the system develops rotational excitations with
      left-right symmetry, corresponding to limit cycles in the 4D phase space, the
      corresponding distribution has the form of a hoop or a tire in the 4D space. In
      the last part we apply the theory to swarms of Brownian particles that are held
      together by weak and attracting forces, which lead to cluster formation. Since
      near the center the potential is at least approximately parabolic and near to the
      radial symmetry, the swarm develops rotational modes of motion with left-right
      symmetry.

PMID- 12188703
TI  - Role of long jumps in surface diffusion.
AB  - We analyze a probability of atomic jumps for more than one lattice spacing in
      activated surface diffusion. First, we studied a role of coupling between the x
      and y degrees of freedom for the diffusion in a two-dimensional substrate
      potential. Simulation results show that in the underdamped limit the average jump
      length <lambda> scales with the damping coefficient eta as <lambda> proportional,
      variant eta(-sigma(lambda)) with 1/2<or=sigma(lambda) less, similar 2/3, so that
      the diffusion coefficient behaves as D proportional, variant eta(-sigma) with
      0<or=sigma less, similar 1/3. Second, we introduced a realistic friction
      coefficient for the phonon damping mechanism and developed the technique for
      Langevin equation with a velocity-dependent friction coefficient. The study of
      diffusion in this model shows that long jumps play an essential role for
      diffusing atoms of small masses, especially in two limiting cases, in the case of
      a large Debye frequency of the substrate, when the rate of phonon damping is low,
      and in the case of a small Debye frequency, when the one-phonon damping mechanism
      is ineffective.

PMID- 12188704
TI  - Pulse propagation sustained by noise in arrays of bistable electronic circuits.
AB  - One-dimensional arrays of nonlinear electronic circuits are shown to support
      propagation of pulses when operating in a locally bistable regime, provided the
      circuits are under the influence of a global noise. These external random
      fluctuations are applied to the parameter that controls the transition between
      bistable and monostable dynamics in the individual circuits. As a result,
      propagating fronts become destabilized in the presence of noise, and the system
      self-organizes to allow the transmission of pulses. The phenomenon is also
      observed in weakly coupled arrays, when propagation failure arises in the absence
      of noise.

PMID- 12188705
TI  - Exactly solvable model with an absorbing state and multiplicative colored
      Gaussian noise.
AB  - We study the temporal evolution of a system that has an absorbing state and that
      is driven by colored Gaussian noise, whose amplitude depends on the system state
      x as [x](alpha). Exact, analytical expressions for the probability density
      functions of the system and of the absorption time are derived. We also calculate
      numerical characteristics of the probability density functions, namely, the
      fractional moments of the system and the mean absorption time, and analyze the
      role of the functional form of the noise correlation function.

PMID- 12188707
TI  - Morphological instability and dynamics of fronts in bacterial growth models with
      nonlinear diffusion.
AB  - Depending on the growth condition, bacterial colonies can exhibit different
      morphologies. As argued by Ben-Jacob et al. there is biological and modeling
      evidence that a nonlinear diffusion coefficient of the type D(b)=D(0)b(k) is a
      basic mechanism that underlies almost all of the patterns and generates a long
      wavelength instability. We study a reaction-diffusion system with a nonlinear
      diffusion coefficient and find that a unique planar traveling front solution
      exists whose velocity is uniquely determined by k and D=D(0)/D(n), where D(n) is
      the diffusion coefficient of the nutrient. Due to the fact that the bacterial
      diffusion coefficient vanishes when b-->0, in the front solution b vanishes in a
      singular way. As a result the standard linear stability analysis for fronts
      cannot be used. We introduce an extension of the stability analysis that can be
      applied to singular fronts, and use the method to perform a linear stability
      analysis of the planar bacteriological growth front. We show that a nonlinear
      diffusion coefficient generates a long-wavelength instability for k>0 and
      D<D(c)(k). We map out the region of stability in the D-k-plane and determine the
      onset of stability that is given by D(c)(k). Both, for D-->0 and k--> infinity
      the dynamics of the growth zone essentially reduces to that of a sharp interface
      problem that is reminiscent of a so-called one-sided growth problem where the
      growth velocity is proportional to the gradient of a diffusion field ahead of the
      interface. The moving boundary approximation that we derive in these limits is
      quite accurate but surprisingly does not become a proper asymptotic theory in the
      strict mathematical sense in the limit D-->0, due to lack of full separation of
      scales on all dynamically relevant length scales. Our linear stability analysis
      and sharp interface formulation will also be applicable to other examples of
      interface formation due to nonlinear diffusion, like in porous media or in the
      problem of vortex motion in superconductors.

PMID- 12188706
TI  - Neutrality condition and response law for nonlinear reaction-diffusion equations,
      with application to population genetics.
AB  - We study a general class of nonlinear macroscopic evolution equations with
      "transport" and "reaction" terms which describe the dynamics of a species of
      moving individuals (atoms, molecules, quasiparticles, organisms, etc.). We
      consider that two types of individuals exist, "not marked" and "marked,"
      respectively. We assume that the concentrations of both types of individuals are
      measurable and that they obey a neutrality condition, that is, the kinetic and
      transport properties of the "not marked" and "marked" individuals are identical.
      We suggest a response experiment, which consists in varying the fraction of
      "marked" individuals with the preservation of total fluxes, and show that the
      response of the system can be represented by a linear superposition law even
      though the underlying dynamics of the system is in general highly nonlinear. The
      linear response law is valid even for large perturbations and is not the result
      of a linearization procedure but rather a necessary consequence of the neutrality
      condition. First, we apply the response theorem to chemical kinetics, where the
      "marked species" is a molecule labeled with a radioactive isotope and there is no
      kinetic isotope effect. The susceptibility function of the response law can be
      related to the reaction mechanism of the process. Secondly we study the
      geographical distribution of the nonrecurrent, nonreversible neutral mutations of
      the nonrecombining portion of the Y chromosome from human populations and show
      that the fraction of mutants at a given point in space and time obeys a linear
      response law of the type introduced in this paper. The theory may be used for
      evaluating the geographic position and the moment in time where and when a
      mutation originated.

PMID- 12188708
TI  - Quasi-two-dimensional dipolar fluid at low densities: Monte Carlo simulations and
      theory.
AB  - We studied a quasi-two-dimensional dipolar fluid in the chaining regime using
      Monte Carlo canonical simulations and theoretical analyses. The self-assembled
      clusters were characterized by measuring their internal energy, conformational
      properties, and equilibrium length distributions. We generalized and used
      equilibrium polymer theory to describe the structure of the chains and rings
      observed in the simulations. The scaling forms of the length distribution
      functions predicted by theory were found to describe adequately the simulation
      results. Finally, we discuss how this type of analysis may be used to establish
      the existence and mechanisms of phase transitions in dilute dipolar fluids.

PMID- 12188709
TI  - Mutual diffusion in a binary Ar-Kr mixture confined within zeolite NaY.
AB  - Molecular dynamics investigations of the mutual diffusion coefficients in an Ar
      Kr mixture confined in the zeolite NaY are reported. Velocity auto- and cross
      correlations were computed at two different temperatures (200 and 600 K). The
      importance of the appropriate choice of reference frame while evaluating the time
      correlation functions is illustrated for argon in the zeolite NaY. Mutual
      diffusivities in the mixture were obtained in the barycentric reference frame.
      Recently, Zhou and Miller showed that the distinct diffusivity D(d) is zero for
      the Ar-Kr mixture in bulk. On confinement, it is seen that at 200 K the ratio
      R=D(11)/D(s)=0.77, where D11 is the mutual diffusivity and D(s) is the mixture
      self-diffusivity. However, at 600 K, R=0.97, implying that the contribution from
      distinct diffusion is only slightly negative. The large negative D(d) at 200 K
      could be attributed to strong localization of Ar and Kr in the physisorption
      sites within the zeolite cages. Analysis of error bars and an efficient
      computational algorithm for evaluation of the velocity cross correlation function
      are also presented. The results have implications in biology, chemistry, and
      other situations where transport of confined mixtures is encountered.

PMID- 12188710
TI  - Fine cohesive powders in rotating drums: Transition from rigid-plastic flow to
      gas-fluidized regime.
AB  - We investigate the dynamics of fine cohesive powders inside rotating drums. We
      show that these powders may be fluidized due to entrapment of ambient gas, and we
      determine the onset of fluidization. Experimental measurements on the bed
      expansion as a function of the rotation velocity have been performed. Drums of
      different diameters and fine powders of varying cohesiveness have been tested. We
      show that (i) fine powders transit directly from a rigid-plastic state to a gas
      fluidized state in accordance with the flow regime boundaries predicted elsewhere
      [A. Castellanos et al., Phys. Rev. Lett. 82, 1156 (1999)], (ii) the onset of
      fluidization in the rotating drum is determined by the ratio of the powder
      kinetic energy per unit volume to its tensile strength, and (iii) once the powder
      is completely fluidized the average interstitial gas velocity increases
      proportionally to the rotation velocity. The last two results imply that the
      required velocity to fluidize a powder, omegaR (omega angular velocity, R radius
      of the drum), must increase as the square root of its tensile strength, and this
      has been confirmed by independent measurements and estimations.

PMID- 12188711
TI  - Transversal inhomogeneities in dilute vibrofluidized granular fluids.
AB  - The spontaneous symmetry breaking taking place in the direction perpendicular to
      the energy flux in a dilute vibrofluidized granular system is investigated, using
      both a hydrodynamic description and simulation methods. The latter include
      molecular dynamics and direct Monte Carlo simulation of the Boltzmann equation. A
      marginal stability analysis of the hydrodynamic equations, carried out in the WKB
      approximation, is shown to be in good agreement with the simulation results. The
      shape of the hydrodynamic profiles beyond the bifurcation is discussed.

PMID- 12188712
TI  - Continuum theory of partially fluidized granular flows.
AB  - A continuum theory of partially fluidized granular flows is developed. The theory
      is based on a combination of the equations for the flow velocity and shear
      stresses coupled with the order-parameter equation which describes the transition
      between the flowing and static components of the granular system. We apply this
      theory to several important granular problems: avalanche flow in deep and shallow
      inclined layers, rotating drums, and shear granular flows between two plates. We
      carry out quantitative comparisons between the theory and experiment.

PMID- 12188714
TI  - Elastic behavior in contact dynamics of rigid particles.
AB  - The systematic errors due to the practical implementation of the contact dynamics
      method for simulation of dense granular media are examined. It is shown that,
      using the usual iterative solver to simulate a chain of rigid particles,
      effective elasticity and sound propagation with a finite velocity occur. The
      characteristics of these phenomena are investigated analytically and numerically
      in order to assess the limits of applicability of this simulation method and to
      compare it with soft particle molecular dynamics.

PMID- 12188713
TI  - Two-dimensional percolation and cluster structure of the random packing of binary
      disks.
AB  - In this paper we study the short-range correlated percolation and the cluster
      structure of two-dimensional (2D) random packing of binary disks with size ratio
      lambda in the range of 1-5. A Monte Carlo simulation model is used to generate
      the configuration of random packing first. Then a from-neighbor-to-neighbor
      propagation method is used to identify the number and sizes of the clusters.
      Results show that for lambda=1 the percolation threshold p(c) lies between the
      square and triangular site percolation thresholds. As lambda increases the
      percolation threshold p(c) (the area fraction of small disks) decreases. To
      characterize the cluster structure at the percolation threshold, we scale the
      cluster size s(c) with the cluster radius R as s(c) proportional, variant R(D).
      The fractal dimension D obtained lies between 1.86 and 1.88 and is independent of
      the size ratio lambda. This value is in good agreement with the 2D theoretical
      fractal dimension which is equal to 91/48.

PMID- 12188715
TI  - Simulational studies of axial granular segregation in a rotating cylinder.
AB  - Discrete particle simulation methods have been used to study axial segregation in
      a horizontal rotating cylinder that is partially filled with a mixture of two
      different kinds of granular particles. Under suitable conditions segregation was
      found to occur, with the particles separating into a series of bands
      perpendicular to the axis. In certain cases the band structure exhibited time
      dependent behavior, including band formation, merging and motion along the axis,
      all corresponding to phenomena that arise experimentally. In order to examine how
      the many parameters specifying the problem affect the segregation process,
      simulation runs were carried out using a variety of parameter settings, including
      combinations of friction coefficients not realizable experimentally. Both
      segregation and desegregation (mixing) were investigated, and cylinders with both
      explicit end caps and periodic ends were used to help isolate the causes of
      segregation.

PMID- 12188716
TI  - Surface tension and nucleation rate of phases of a charged colloidal suspension.
AB  - The square gradient approximation is used to calculate the surface tension
      between two phases of differing density in a charged colloidal suspension, and
      the results are compared with experimental and theoretical evidence from various
      colloidal systems. The nucleation rate of a colloidal liquid cluster from a
      metastable colloidal gas is estimated using a version of classical nucleation
      theory. We explain in terms of nucleation phenomena the recently described "Swiss
      cheese effect," which involves the formation of crystals from an initial
      disordered state, followed by the formation of disordered regions within the
      crystals and at the interfaces between them. We argue that this sequence of
      events shows evidence both of homogeneous and of heterogeneous nucleation. The
      experimental prominence of homogeneous nucleation suggests that metastability is
      very important in colloidal systems, and therefore that the consideration of
      nucleation rates is essential to the study of phase behavior in such systems. We
      also predict that the occurrence or nonoccurrence of phase separation into a
      dense and a rarefied phase is governed by the ratio of the macroion charge to the
      macroion radius.

PMID- 12188717
TI  - Volume-term theories, Sogami-Ise potential, and the Langmuir model for phase
      separation in macroion systems: a resolution.
AB  - There is a controversy regarding the mechanism of phase separation in highly
      charged macroion systems. Volume-term (VT) theories propose that the transition
      is due to a spinodal instability sensitive only by the microions, the Sogami-Ise
      theory gives an attractive tail in the pair interaction potential, which promotes
      the formation of clusters and voids, and the Langmuir (L) model views the
      transition as an instability of the pressure. It is shown herein that these three
      seemingly different models can be brought under the same formalism and that they
      reflect different contributions to the same overall process. Within the context
      of the VT formalism, the attractive tail in the macroion-macroion pair
      interaction is a direct result of the screened Coulomb form of the interaction
      and is identified as a microion-modified electrostatic pressure. Within the
      context of the VT formalism the L theory is associated with the microion-microion
      interaction for the added electrolyte. Finally this holistic view of the VT
      approach is extended to include the contribution of the solvent via the Gibbs
      Duhem expression.

PMID- 12188718
TI  - Electrostatic interaction between two aqueous microdroplets in an apolar medium.
AB  - In an apolar medium, the electrostatic interactions between two aqueous
      microdroplets coated with surfactants are investigated by the mean-field theory.
      The electric field and ion distributions within the aqueous core are described by
      the Poisson-Boltzmann equation. Under Debye-Huckel approximation, the interaction
      energy is obtained analytically. Due to the polarization effect, the Coulomb
      interaction is altered by the induced multipoles in the aqueous droplet. The
      interaction, however, is insensitive to the ion concentration. In comparison with
      the Coulomb interaction, the repulsion for a pair of similarly charged droplets
      is reduced and the attraction for a pair of oppositely charged droplets is
      enhanced. More importantly, the interaction between a neutral and charged
      droplets is attractive. The effect of interdroplet interactions on the collision
      frequency is also discussed.

PMID- 12188719
TI  - Foam drainage: a film contribution?
AB  - We have measured the steady drainage of foams of various surfactants, varying the
      size of the parietal plateau borders from 0.24 to 2.4 mm. We report an evolution
      of the power laws of drainage with the bubble size, which cannot be explained by
      the most recent developments of the drainage theory. We believe that one reason
      for the disagreement between the existing theory and our data is the passage of
      liquid through the films, from nodes to nodes. Film thickness measurements in
      situ show that the films are swollen, up to 2 microm and more. Films, usually
      neglected, may then have an important contribution to drainage by increasing
      noticeably the volume of the regions where the liquid flows.

PMID- 12188720
TI  - Energy and symmetry of self-assembled two-dimensional dipole clusters in magnetic
      confinement.
AB  - We report on confined two-dimensional (2D) dipole clusters formed by small
      ferromagnetic particles floating at the liquid-air interface and confined by
      nonuniform external magnetic field. The particles self assemble into hexagonally
      ordered clusters whose lattice constant can be magnetically tuned. We study the
      area S, the energy E, the chemical potential mu and the lattice constant a, of 2D
      clusters as functions of particle number N for N<130. We develop a continuum
      approximation which accounts fairly well for the smooth part of mu(N), S(N), and
      a(N) dependences. In addition to these dependences, we observe quasiperiodic
      fluctuations with dips at "magic" numbers corresponding to particularly symmetric
      particle configurations. We demonstrate that these fluctuations are related to
      the cluster symmetry and to the cluster center of mass position.

PMID- 12188721
TI  - Theory of structural transformations in ferrofluids: chains and "gas-liquid"
      phase transitions.
AB  - We consider a ferrofluid consisting of identical spherical particles with a
      permanent magnetic moment. Under the assumption that linear flexible chains can
      appear in the ferrofluid, we estimate the distribution function of the number of
      particles inside the chain. The analysis is done and simple expressions for the
      size distribution function are obtained in asymptotics of a strong magnetic
      interaction between the particles inside one chain. We studied the influence of
      the linear chains on conditions and scenarios of bulk "gas-liquid" phase
      transition in the ensemble of the particles under an infinitely strong magnetic
      field. In order to study the influence of the chains on bulk "gas-liquid" phase
      transition in the ensemble of the particles, their chemical potential mu is
      calculated in the model of separate interacting particles as well as in the model
      with chains, taking into account the interaction between them. When the
      temperature is low enough, van der Waals loops appear on the plots of mu versus
      volume concentration phi of the particles in the first model; function mu(phi)
      increases monotonically in the second model for all examined temperatures. This
      means that the condensation "gas-liquid" phase transition can take place in the
      model of individual particles; however, formation of the chains in real
      ferrofluids prevents the appearance of this transition.

PMID- 12188723
TI  - Viscosity of bimodal and polydisperse colloidal suspensions.
AB  - We present a theoretical framework for the viscosity of bimodal and polydisperse
      colloidal suspensions. For colloidal dispersions both interparticle forces
      between pairs of particles and many-particle effects such as depletion forces can
      have a significant effect on rheology. As hydrodynamic interactions are also
      important for colloidal systems, a theoretical description that includes
      hydrodynamic and thermodynamic interactions is required. An integral equation
      theory for multicomponent systems accounts for the contribution of thermodynamic
      interactions to the viscosity of dispersions. Introduction of small particles
      into a system of larger particles causes depletion forces between the large
      particles that increase the viscosity, while replacing large particles with an
      equal volume fraction of small particles increases the free volume in the system
      and decreases the viscosity. The integral equations model both of these effects
      in concentrated suspensions and provide a microscopic interpretation of free
      volume changes as changes in radial distribution functions. For a bimodal mixture
      they predict a dependence of the viscosity on size ratio, composition, and total
      volume fraction. Polydispersity is modeled by a small number of components whose
      sizes and weights are chosen to match the moments of the size distribution. This
      theory predicts a reduction in viscosity due to polydispersity and explains
      conflicting experimental measurement of the viscosity of hard-sphere colloids.
      Existing theoretical approaches that neglect the multiparticle correlations,
      included through the integral equations, yield qualitatively incorrect results
      for the change in the viscosity relative to monodisperse systems.

PMID- 12188722
TI  - Effective forces in colloidal mixtures: from depletion attraction to accumulation
      repulsion.
AB  - Computer simulations and theory are used to systematically investigate how the
      effective force between two big colloidal spheres in a sea of small spheres
      depends on the basic (big-small and small-small) interactions. The latter are
      modeled as hardcore pair potentials with a Yukawa tail which can be either
      repulsive or attractive. For a repulsive small-small interaction, the effective
      force follows the trends as predicted by a mapping onto an effective nonadditive
      hardcore mixture: both a depletion attraction and an accumulation repulsion
      caused by small spheres adsorbing onto the big ones can be obtained depending on
      the sign of the big-small interaction. For repulsive big-small interactions, the
      effect of adding a small-small attraction also follows the trends predicted by
      the mapping. But a more subtle "repulsion through attraction" effect arises when
      both big-small and small-small attractions occur: upon increasing the strength of
      the small-small interaction, the effective potential becomes more repulsive. We
      have further tested several theoretical methods against our computer simulations:
      The superposition approximation works best for an added big-small repulsion, and
      breaks down for a strong big-small attraction, while density functional theory is
      very accurate for any big-small interaction when the small particles are pure
      hard spheres. The theoretical methods perform most poorly for small-small
      attractions.

PMID- 12188724
TI  - Electrically induced interactions between colloidal particles in the vicinity of
      a conducting plane.
AB  - We address the problem of two-dimensional (2D) colloidal aggregation driven by an
      ac electrical field, by observing an aqueous dispersion of latex microspheres in
      contact with a conducting surface. Using micron-sized carboxylated polystyrene
      particles, we have systematically investigated the aggregation process, as a
      function of particle size and charge, and of the applied electric field amplitude
      and frequency. A low-density 2D phase is observed at high frequency (typically
      above 1 kHz), while at low frequency (below a "contact frequency" nu(c)) the
      collection of particles collapses into disconnected compact aggregates of
      crystalline (hexagonal) structure. We argue that this scenario is governed by the
      competition between an attractive force, of electrohydrodynamic nature, and a
      repulsive force, basically an electrical dipole-dipole interaction. Both
      contributions are revealed and analyzed in independent experiments on isolated
      particle pairs, using optical manipulation and dynamometry.

PMID- 12188725
TI  - Demixing of colloid-polymer mixtures in poor solvents.
AB  - The influence of poor solvent quality on fluid demixing of a model mixture of
      colloids and nonadsorbing polymers is investigated using density functional
      theory. The colloidal particles are modeled as hard spheres and the polymer coils
      as effective interpenetrating spheres that have hard interactions with the
      colloids. The solvent is modeled as a two-component mixture of a primary solvent,
      regarded as a background theta solvent for the polymer, and a cosolvent of point
      particles that are excluded from both colloids and polymers. Cosolvent exclusion
      favors overlap of polymers, mimicking the effect of a poor solvent by inducing an
      effective attraction between polymers. For this model, a geometry-based density
      functional theory is derived and applied to bulk fluid phase behavior. With
      increasing cosolvent concentration (worsening solvent quality), the predicted
      colloid-polymer demixing binodal shifts to lower colloid concentrations,
      promoting demixing. For sufficiently poor solvent, a reentrant demixing
      transition is predicted at low colloid concentrations.

PMID- 12188726
TI  - Phase separation in two-dimensional binary fluid mixtures: spontaneous pinning
      effect.
AB  - The dynamics of phase separation, under asymmetric quench, is studied for binary
      mixtures by molecular dynamics simulations. We consider two kinds of systems,
      i.e., the small molecular liquid mixture and the flexible chain blend. The domain
      growth is found to be dependent crucially upon the relative composition of the
      mixture. For a near symmetric quench with volume fraction not far away from the
      critical value, we find that the domain growth is obviously slowed down (the
      spontaneous pinning effect) when the phase-separating structure undergoes the
      percolation-to-cluster transition. However, as the volume fraction of the
      minority phase is decreased, a pinning-depinning transition of the domain growth
      is observed for certain asymmetric quenches, due to the correlated motion of
      droplets. For sufficiently asymmetric quenches where the volume fraction of the
      minority phase is low, the domain growth is suppressed at late stages for the
      flexible polymer blend, in contrast to the fast growth for the small molecular
      system. The results are in good agreement with previous studies, and confirm the
      possibility of the intermittent or final pinning of phase separation for isolated
      droplets structure.

PMID- 12188727
TI  - Delocalization transitions of semiflexible manifolds.
AB  - Semiflexible manifolds such as fluid membranes or semiflexible polymers undergo
      delocalization transitions if they are subject to attractive interactions. We
      study manifolds with short-ranged interactions by field-theoretic methods based
      on the operator product expansion of local interaction fields. We apply this
      approach to manifolds in a random potential. Randomness is always relevant for
      fluid membranes, while for semiflexible polymers there is a first-order
      transition to the strong coupling regime at a finite temperature.

PMID- 12188728
TI  - Kinetic bottleneck to the self-organization of bidisperse hard disk monolayers
      formed by random sequential adsorption.
AB  - We study the self-organization of bidisperse mixtures of hard spheres in two
      dimensions by simulating random sequential adsorption (RSA) of tethered hard
      disks that undergo limited Monte Carlo surface diffusion. The tethers place a
      control on the local entropy of the disks by constraining their movement within a
      specified distance from their original adsorption positions. By tuning the tether
      length, from zero (the pure RSA process) to infinity (near-equilibrium
      conditions), the kinetic pathway to monolayer formation can be varied. Previously
      [J. J. Gray et al., Phys. Rev. Lett. 85, 4430 (2000); Langmuir 17, 2317 (2001)],
      we generated nonequilibrium phase diagrams for size-monodisperse and size
      polydisperse hard disks as a function of surface coverage, size distribution, and
      tether length to reveal the occurrence of hexagonal close-packed, hexatic, and
      disordered phases. Bidisperse hard disks potentially offer increasingly diverse
      phase diagrams, with the possible occurrence of spatially and compositionally
      organized superlattices. Geometric packing calculations anticipate the formation
      of close-packed lattices in two dimensions for particle size ratios
      sigma=R(S)/R(L)=0.53, 0.414, and 0.155. The simulations of these systems
      presented here, however, reveal that RSA kinetics frustrate superlattice
      ordering, even for infinite tethers. The calculated jamming limits fall well
      below the minimum surface coverages necessary for stable ordering, as determined
      by melting simulations.

PMID- 12188729
TI  - Phase diagram of symmetric binary fluid mixtures: first-order or second-order
      demixing.
AB  - Binary fluid mixtures of 1:1 concentration can demix in a phase transition of
      first order or of second order. We analyze the two scenarios in density
      concentration space and relate them to the structure of the line at which the
      demixing coexistence surface cuts the liquid-vapor coexistence surface. These
      scenarios help us to decide between first and second order for a model of a
      symmetric Lennard-Jones mixture. An optimized reference hypernetted chain
      integral equation method is employed for calculating the correlation functions
      and from there the pressure and chemical potentials. We conclude that demixing of
      a 1:1 mixture is of first order in the whole range of parameters that we have
      investigated. We did not find a critical point in the 1:1 concentration plane.

PMID- 12188730
TI  - Coherent scattering function in the reptation model: analysis beyond asymptotic
      limits.
AB  - We calculate the coherent dynamical scattering function S(c)(q,t;N) of a flexible
      chain of length N, diffusing through an ordered background of topological
      obstacles. As an instructive generalization, we also calculate the scattering
      function S(c)(q,t;M,N) for the central piece of length M<or=N of the chain. Using
      the full reptation model, we treat global creep, tube length fluctuations, and
      internal relaxation within a consistent and unified approach. Our theory
      concentrates on the universal aspects of reptational motion, and our results in
      all details show excellent agreement with our simulations of the Evans-Edwards
      model, provided we allow for a phenomenological prefactor which accounts for
      nonuniversal effects of the microstructure of the Monte Carlo chain, present for
      short times. Previous approaches to the coherent structure function can be
      analyzed as special limits of our theory. First, the effects of internal
      relaxation can be isolated by studying the limit N--> infinity, M fixed. The
      results do not support the model of a "Rouse chain in a tube." We trace this back
      to the nonequilibrium initial conditions of the latter model. Second, in the
      limit of long chains (M=N--> infinity ) and times large compared to the internal
      relaxation time (t/N(2)--> infinity ), our theory reproduces the results of the
      primitive chain model. This limiting form applies only to extremely long chains,
      and for chain lengths accessible in practice, effects of, e.g., tube length
      fluctuations are not negligible.

PMID- 12188731
TI  - Critical behavior of ionic liquids.
AB  - The renormalization of the Landau-Ginzburg Hamiltonian for a system with
      Coulombic interactions caused by spatially inhomogeneous polarizational effects
      is discussed. It is shown that for ionic liquids with a strong dependence of the
      degree of dissociation on density, the nonclassical fluctuation region is
      significantly narrowed. The essential role of the association of ions is noted.

PMID- 12188732
TI  - Concentration fluctuations in the binary mixture hexane-nitrobenzene with static
      and dynamic x-ray scattering.
AB  - We report on a small-angle x-ray scattering study of the hexane-nitrobenzene
      binary fluid mixture near its critical point. The use of an ultrabright x-ray
      undulator synchrotron source enabled us to measure the temperature dependence of
      the static structure factor with unprecedented contrast, and the large coherent
      flux of this source provided a probe for the fluctuation dynamics via the x-ray
      photon correlation spectroscopy technique. We find that the intensity and
      correlation lengths diverge with the expected three-dimensional Ising critical
      exponents, and the dynamical correlation function decays exponentially with
      correlation times as small as 250 micros. In the range of wave vector studied
      here (1.2-2.6 x 10(-3) A(-1)) the concentration fluctuations relaxed diffusively
      with a diffusion constant consistent with that determined from visible light
      scattering measurements.

PMID- 12188733
TI  - Nonequilibrium Brownian dynamics analysis of negative viscosity induced in a
      magnetic fluid subjected to both ac magnetic and shear flow fields.
AB  - We study the rheological and magnetic characteristics of a magnetic fluid. The
      system, which we investigate, is as follows. Ferromagnetic particles are
      dispersed in a solvent, which is subjected to both ac magnetic and shear flow
      fields. The translational and rotational motions of particles are calculated by
      the Brownian dynamics method based on Langevin equations and the rheological and
      magnetic characteristics of the magnetic fluid system are estimated. First, we
      investigate the rheological and magnetic characteristics of the system in a dc
      magnetic field and then we analyze the effect of an ac magnetic field on those
      characteristics. We find that the negative viscosity effect is induced at a
      certain frequency range of the ac magnetic field. We also find that there are two
      main mechanisms responsible for the occurrence of negative viscosity. (1)
      Resonance between the rotational motions of the dipoles of particles and the
      fluctuation of ac magnetic fields occurs when applied magnetic fields are weak
      compared to the shear rate, in which case particles can still rotate in magnetic
      fields. Beyond this resonance frequency, negative viscosity appears. (2) The
      magnetic dipole moments of particles are forced to stay in the direction of the
      magnetic field when strong magnetic fields are applied in relatively low shear
      flow fields. However, negative viscosity occurs when the frequency of external
      magnetic fields exceeds a critical value, in which case the dipoles rotate
      continuously in a shear flow without stopping. In both cases, the mean angular
      velocity of the particles becomes higher than that of the solvent.

PMID- 12188734
TI  - Faraday instability on viscous ferrofluids in a horizontal magnetic field:
      oblique rolls of arbitrary orientation.
AB  - A linear stability analysis of the free surface of a horizontally unbounded
      ferrofluid layer of arbitrary depth subjected to vertical vibrations and a
      horizontal magnetic field is performed. A nonmonotonic dependence of the
      stability threshold on the magnetic field is found at high frequencies of the
      vibrations. The reasons for the decrease of the critical acceleration amplitude
      caused by a horizontal magnetic field are discussed. It is revealed that the
      magnetic field can be used to select the first unstable pattern of Faraday waves.
      In particular, a rhombic pattern as a superposition of two different oblique
      rolls can occur. A scaling law is presented which maps all data into one graph
      for the tested range of viscosities, frequencies, magnetic fields, and layer
      thicknesses.

PMID- 12188735
TI  - H-function representations for stretched exponential relaxation and non-Debye
      susceptibilities in glassy systems.
AB  - Analytical expressions in the time and frequency domains are derived for non
      Debye relaxation processes. The complex frequency-dependent susceptibility
      function for the stretched exponential relaxation function is given for general
      values of the stretching exponent in terms of H-functions. The relaxation
      functions corresponding to the complex frequency-dependent Cole-Cole, Cole
      Davidson, and Havriliak-Negami susceptibilities are given in the time domain in
      terms of H-functions. It is found that a commonly used correspondence between the
      stretching exponent of Kohlrausch functions and the stretching parameters of
      Havriliak-Negami susceptibilities are not generally valid.

PMID- 12188736
TI  - Intermembrane spacing and velocity profiling of a lamellar lyotropic complex
      fluid under flow using x-ray diffraction.
AB  - We report on the use of x-ray diffraction as a means of extracting velocity
      profiles from a non-Newtonian complex fluid under laminar flow. In particular, we
      applied this technique to a concentrated undulating membrane system flowing
      through a cylindrical capillary tube. The intermembrane separation d was measured
      as a function of simple shear using a Couette flow cell. A logarithmic dependence
      of d as a function of the shear rate was observed, while there was a linear
      relationship between the fractional intermembrane spacing and the shear stress.
      Subsequent measurement of the system's intermembrane spacing as a function of
      position within the cylindrical flow pipe allowed for the calculation of a shear
      rate profile within the capillary. Simple numerical integration then yielded an
      accurate velocity profile of the fluid flowing through the pipe. Both shear
      thickening and plug flow shear thinning profiles were observed.

PMID- 12188737
TI  - Adaptive phase field simulation of dendritic growth in a forced flow at various
      supercoolings.
AB  - An efficient finite volume method is developed for the phase-field simulation of
      two-dimensional dendritic growth in a forced flow at various supercoolings. The
      adaptive nature of the method allows the dendrite in a large domain to evolve
      secondary structures, even at low supercoolings. In addition to good agreement
      with previous calculations on the tip shape and speed, the effects of forced flow
      at various supercoolings are investigated and compared with the Oseen-Ivantsov
      solution and good agreement is found. The steady dendrite shape in all cases
      continues to have a self-affine nature and the invariant scaling parameters are
      in good agreement with the estimation.

PMID- 12188738
TI  - Monte Carlo study of the elastic interaction in heteroepitaxial growth.
AB  - We have studied the island-size distribution and spatial correlation function of
      an island growth model under the effect of an elastic interaction of the form
      1/r(3). The mass distribution P(n)(t) that was obtained presents a pronounced
      peak that widens with the increase of the total coverage of the system, theta.
      The presence of this peak is an indication of the self-organization of the
      system, since it demonstrates that some sizes are more frequent than others. We
      have treated exactly the energy of the system using periodic boundary conditions
      that were used in the Monte Carlo simulations. A discussion about the effect of
      different factors is presented.

PMID- 12188739
TI  - Electrostatic fluctuations in soap films.
AB  - A field theory to describe electrostatic interactions in soap films, described by
      electric multilayers with a generalized thermodynamic surface-charging mechanism,
      is studied. In the limit where the electrostatic interactions are weak, this
      theory is exactly soluble. The theory incorporates in a consistent way, the
      surface-charging mechanism and the fluctuations in the electrostatic field that
      correspond to the zero-frequency component of the van der Waals force. It is
      shown that these terms lead to a Casimir-like attraction that can be sufficiently
      large to explain the transition between the common black film to a Newton black
      film.

PMID- 12188740
TI  - Solid-liquid interface of a 2-propanol-perfluoromethylcyclohexane mixture: from
      adsorption to wetting.
AB  - The liquid-solid interface between a silicon substrate and the binary mixture
      perfluoromethylcyclohexane (PFMC) and 2-propanol (IP) is examined by x-ray
      specular reflectivity and diffuse scattering under grazing angles. The wetting
      films between the PFMC-rich phase and the substrate are characterized with
      respect to the density profile and lateral fluctuations. We find that the liquid
      liquid interface of the film is anomalously broadened as compared to capillary
      wave theory. This broadening is caused by a locally slow variation of the density
      between the liquid phases and marks an adsorption profile that does not reflect
      the bulk properties of the film phase. Essentially the same behavior is present
      for a fused silica substrate.

PMID- 12188741
TI  - Simple model of capillary condensation in porous media.
AB  - We employ a simple model to describe the phase behavior of 4He and Ar in a
      hypothetical porous material consisting of a regular array of infinitely long,
      solid, parallel cylinders. We find that high porosity geometries exhibit two
      transitions: from vapor to film and from film to capillary condensed liquid. At
      low porosity, the film is replaced by a "necking" configuration, and for a range
      of intermediate porosity there are three transitions: from vapor to film, from
      film to necking and from necking to a capillary condensed phase.

PMID- 12188742
TI  - Roughness-induced filling.
AB  - We study adsorption of a fluid on a periodically corrugated substrate using the
      mean-field version of the effective Hamiltonian approach. We analyze the shape of
      the interface close to the wetting point of a planar substrate, and the free
      energy of the system as a function of temperature and amplitude of the
      corrugation for short-range and long-range interactions. We prove that the
      substrate roughness has no influence on the locus and order of the wetting
      transition, when the planar substrate of the same chemical composition as the
      corrugated one experiences critical wetting. For short-range interactions we
      observe the corrugation driven filling transition. We show analytically that a
      thin-thick first-order transition occurs when the corrugation amplitude of the
      substrate exceeds a critical value. The phase diagram of the adsorption on a
      sinusoidally corrugated substrate at the bulk liquid-gas coexistence is obtained.

PMID- 12188743
TI  - Lattice model of gas condensation within nanopores.
AB  - We explore the thermodynamic behavior of gases adsorbed within a nanopore. The
      theoretical description employs a simple lattice gas model, with two species of
      site, expected to describe various regimes of adsorption and condensation
      behavior. The model includes four hypothetical phases: a cylindrical shell phase
      (S), in which the sites close to the cylindrical wall are occupied, an axial
      phase (A), in which sites along the cylinder's axis are occupied, a full phase
      (F), in which all sites are occupied, and an empty phase (E). We obtain exact
      results at T=0 for the phase behavior, which is a function of the interactions
      present in any specific problem. We obtain the corresponding results at finite T
      from mean field theory. Finally, we examine the model's predicted phase behavior
      of some real gases adsorbed in nanopores.

PMID- 12188744
TI  - X-ray scattering of thin liquid films: beyond the harmonic approximation.
AB  - We calculate the x-ray scattering from coupled capillary fluctuations of thin
      liquid films, taking into account an asymmetric interfacial interaction
      potential. Harmonic expansion of the potential around its minimum produces the
      well-known Kiessig fringes in both specular reflectivity and longitudinal diffuse
      scattering. The addition of a cubic term to the expansion, representing the
      asymmetry, leads to q(z)-dependent changes of the modulation period of the
      Kiessig fringes. The cubic term produces a relative phase shift between the
      interference fringes of the specular reflectivity and the off-specular
      longitudinal diffuse scattering. It is suggested that these effects may be used
      to estimate, via x-ray scattering, the interfacial potential of thin liquid
      films.

PMID- 12188745
TI  - Anisotropic self-diffusion in thermotropic liquid crystals studied by 1H and 2H
      pulse-field-gradient spin-echo NMR.
AB  - The molecular self-diffusion coefficients in nematic and smectic-A thermotropic
      liquid crystals are measured using stimulated-echo-type 2H and 1H pulse-field
      gradient spin-echo nuclear magnetic resonance (PGSE NMR) combined with multiple
      pulse dipolar decoupling and slice selection. The temperature dependence of the
      principal components of the diffusion tensor in the nematic phase follows a
      simple Arrhenius relationship except in the region of nematic-isotropic phase
      transition where it reflects, merely, the decrease of the molecular orientational
      order. The average of the principal diffusion coefficients in the isotropic
      nematic phase transition region is close to the diffusion coefficient in the
      isotropic phase. At the nematic-smectic-A phase transition the diffusion
      coefficients change continuously. The results in nematic phase are best described
      in terms of the affine transformation model for diffusion in nematics formed by
      hard ellipsoids. In the smectic-A phase the data are interpreted using a modified
      model for diffusion in presence of a periodic potential along the director.

PMID- 12188746
TI  - Liquid correlation across the walls in a slit pore: effect on the wetting and
      drying transition.
AB  - The liquid structure next to the walls of a slit pore, immersed in a model simple
      liquid, is studied through a liquid theory and grand canonical Monte Carlo
      simulations. A liquid correlation across slit walls, of finite width, is found.
      This correlation modifies the structure and capillary partial wetting and drying
      transitions of the nonhomogeneous fluid, when close to its liquid-vapor
      coexistence curve.

PMID- 12188747
TI  - Enantiomeric excess dependence of the phase diagram of antiferroelectric liquid
      crystals.
AB  - The phase diagram of the prototype antiferroelectric liquid crystal 4-(1
      methylheptyloxycarbonyl)phenyl-4'-octyloxybiphengl-4-carboxylate (MHPOBC) in
      dependence of enantiomeric excess was measured. It was shown that the Sm-C*beta
      phase in very pure samples is the Sm-C*(FI2) phase with a four-layer structure,
      and only after small racemization it transforms into the ferroelectric Sm-C*
      phase. The phase diagram was theoretically explained by taking into account
      longer range bilinear and short range biquadratic interlayer interactions, that
      lead to the distorted clock structures and first-order transitions between them.

PMID- 12188748
TI  - Electroclinic effect and modulated phases in smectic liquid crystals.
AB  - We explore the possibility that the unusually large electroclinic effect observed
      in the smectic-A phase of a ferroelectric liquid crystal arises from the presence
      of an ordered array of disclination lines and walls in a smectic-C* phase. If the
      spacing of these defects is in the subvisible range, this modulated smectic-C*
      phase would be similar macroscopically to a smectic-A phase. The application of
      an electric field distorts the array, producing a large polarization, and hence a
      large electroclinic effect. We show that with suitable elastic parameters and
      sufficiently large chirality, the modulated phase is favored over the smectic-A
      and helically twisted smectic-C* phases. We propose various experimental tests of
      this scenario.

PMID- 12188749
TI  - Structure and dynamics of freely suspended film of the smectic-C*alpha phase in
      an external transverse electric field.
AB  - We present a theoretical analysis of static and dynamic properties of freely
      suspended films of the smectic-C*alpha phase in an external electric field,
      applied along the smectic layers. The analysis is performed within the "clock"
      model, where the interactions up to next-nearest neighbors are considered. The
      calculated critical electric field for the unwinding of the smectic-C*alpha phase
      is of the order of several 100 V/mm and strongly depends on the interlayer
      interactions. The calculated relaxation rates of the eigenfluctuations of a
      system of N layers are in the kilohertz range for phase fluctuations and several
      megahertz for amplitude fluctuations.

PMID- 12188750
TI  - Detailed analysis of the induction period of polymer crystallization by
      depolarized light scattering.
AB  - In order to clarify the structure formation processes in the induction period of
      polymer crystallization the annealing time dependence of depolarized light
      scattering (DPLS) intensities has been investigated as a function of
      crystallization temperature for poly(ethylene terephthalate), poly(ethylene
      naphthalate), syndiotactic polystyrene, and isotactic polystyrene. It is found
      that the induction period may be separated into three stages: the first stage
      where the DPLS intensity hardly changes with time, the second stage where the
      intensity increases exponentially, and the third stage where it levels off.
      Considering that the DPLS provides information about the degree of parallel
      orientation of rigid polymer segments, the first stage whose time length depends
      on the annealing temperature may be assigned to a process where the polymer
      chains begin to partially assume a rigid conformation, generally a helical
      structure being almost the same as the structure in the corresponding crystal.
      This process is limited to a time when the average length of the rigid segments
      attains a critical value given by a Shimada, Doi, and Okano theory [J. Chem.
      Phys. 88, 7181 (1988)] above which spinodal decomposition (SD) is caused. The
      second and third stages correspond to the early and late stages of SD,
      respectively, which was confirmed by small-angle x-ray scattering measurements.
      The apparent activation energies obtained from the temperature dependence of the
      DPLS intensities for the three stages were 35-40, 25-50, and 180-400 kJ/mol,
      respectively, for all the polymers. The large apparent activation energies for
      the late stage of SD is discussed within a framework of Binder and Stauffer's
      theory [Phys. Rev. Lett. 33, 1006 (1974)].

PMID- 12188751
TI  - Universal aspects of macromolecules in polymer blends, solutions, and
      supercritical mixtures.
AB  - We demonstrate that macromolecules in miscible polymer blends may behave as good,
      Theta, and poor polymeric solvents for each other. We construct a conceptual
      phase diagram, delineating the range of validity of the random-phase
      approximation, outside of which polymers contract or expand beyond their
      unperturbed dimensions, contrary to common assumptions. Remarkably, the
      correlation length for polymer blends, solutions, and supercritical mixtures
      collapses onto a master curve, reflecting universal behavior for macromolecules
      in polymeric and small-molecule Theta solvents.

PMID- 12188752
TI  - Metastable lattice of droplets in phase separating polymer blends.
AB  - Phase separation in a polymer mixture with an off-critical composition is
      described by a Ginzburg-Landau Hamiltonian that contains both cubic and quartic
      terms in the deviation of composition from its mean value in the homogeneous
      phase. Our analysis suggests that when a blend is brought in the vicinity of the
      spinodal, the initial homogeneous phase becomes unstable against the formation of
      a metastable lattice of spherical droplets whose lifetime diverges in the limit
      of infinite molecular weight. The composition of the droplets approaches that of
      the background phase and their size diverges with the approach to the critical
      point, but the composition contrast is enhanced and droplet radii become
      comparable to polymer dimensions, away from criticality. The connection between
      our predictions and the results of recent neutron scattering experiments is
      discussed, and new experiments that could probe the proposed droplet lattice are
      proposed.

PMID- 12188753
TI  - Quantum computation in brain microtubules: decoherence and biological
      feasibility.
AB  - The Penrose-Hameroff orchestrated objective reduction (orch. OR) model assigns a
      cognitive role to quantum computations in microtubules within the neurons of the
      brain. Despite an apparently "warm, wet, and noisy" intracellular milieu, the
      proposal suggests that microtubules avoid environmental decoherence long enough
      to reach threshold for "self-collapse" (objective reduction) by a quantum gravity
      mechanism put forth by Penrose. The model has been criticized as regards the
      issue of environmental decoherence, and a recent report by Tegmark finds that
      microtubules can maintain quantum coherence for only 10(-13) s, far too short to
      be neurophysiologically relevant. Here, we critically examine the decoherence
      mechanisms likely to dominate in a biological setting and find that (1) Tegmark's
      commentary is not aimed at an existing model in the literature but rather at a
      hybrid that replaces the superposed protein conformations of the orch. OR theory
      with a soliton in superposition along the microtubule; (2) recalculation after
      correcting for differences between the model on which Tegmark bases his
      calculations and the orch. OR model (superposition separation, charge vs dipole,
      dielectric constant) lengthens the decoherence time to 10(-5)-10(-4) s; (3)
      decoherence times on this order invalidate the assumptions of the derivation and
      determine the approximation regime considered by Tegmark to be inappropriate to
      the orch. OR superposition; (4) Tegmark's formulation yields decoherence times
      that increase with temperature contrary to well-established physical intuitions
      and the observed behavior of quantum coherent states; (5) incoherent metabolic
      energy supplied to the collective dynamics ordering water in the vicinity of
      microtubules at a rate exceeding that of decoherence can counter decoherence
      effects (in the same way that lasers avoid decoherence at room temperature); (6)
      microtubules are surrounded by a Debye layer of counterions, which can screen
      thermal fluctuations, and by an actin gel that might enhance the ordering of
      water in bundles of microtubules, further increasing the decoherence-free zone by
      an order of magnitude and, if the dependence on the distance between
      environmental ion and superposed state is accurately reflected in Tegmark's
      calculation, extending decoherence times by three orders of magnitude; (7)
      topological quantum computation in microtubules may be error correcting,
      resistant to decoherence; and (8) the decohering effect of radiative scatterers
      on microtubule quantum states is negligible. These considerations bring
      microtubule decoherence into a regime in which quantum gravity could interact
      with neurophysiology.

PMID- 12188754
TI  - Self-trapping versus trapping: application to hole transport in DNA.
AB  - We address the problem of interplay between self-trapping effects and effects of
      an external potential, which may be relevant for many physical systems, such as
      polarons in solids or a Bose-Einstein condensate with attraction. If the
      potential consists of two different wells, the system initially localized in the
      shallower well may relax into the deeper well, or may not if stabilized by the
      self-trapping effect. We show how this picture can be applied to interpret
      results of recent experiments on electron transfer in the DNA molecule [Giese et
      al., Nature 412, 318 (2001)]. The results of our calculations agree well with the
      experimental findings, giving evidence that hole transport in DNA involves
      polaronic effects.

PMID- 12188755
TI  - Electrical characterization of gel collected from shark electrosensors.
AB  - To investigate the physical mechanism of the electric sense, we present an
      initial electrical characterization of the glycoprotein gel that fills the
      electrosensitive organs of marine elasmobranchs (sharks, skates, and rays). We
      have collected samples of this gel, postmortem, from three shark species, and
      removed the majority of dissolved salts in one sample via dialysis. Here we
      present the results of dc conductivity measurements, low-frequency impedance
      spectroscopy, and electrophoresis. Electrophoresis shows a range of large protein
      based molecules fitting the expectations of glycoproteins, but the gels of
      different species exhibit little similarity. The electrophoresis signature is
      unaffected by thermal cycling and measurement currents. The dc data were
      collected at various temperatures, and at various electric and magnetic fields,
      showing consistency with the properties of seawater. The impedance data collected
      from a dialyzed sample, however, show large values of static permittivity and a
      loss peak corresponding to an unusually long relaxation time, about 1 ms. The
      exact role of the gel is still unknown, but our results suggest its bulk
      properties are well matched to the sensing mechanism, as the minimum response
      time of an entire electric organ is on the order of 5 ms.

PMID- 12188756
TI  - Metastable intermediates in the condensation of semiflexible polymers.
AB  - Motivated by results from an earlier Brownian dynamics simulation for the
      collapse of a single, stiff polymer in a poor solvent [B. Schnurr, F. C.
      MacKintosh, and D. R. M. Williams, Europhys. Lett. 51, 279 (2000)] we calculate
      the conformational energies of the intermediate (racquet) states suggested by the
      simulations. In the absence of thermal fluctuations (at zero temperature) the
      annealed shapes of these intermediates are well-defined in certain limits, with
      their major structural elements given by a particular case of Euler's elastica.
      In appropriate units, a diagram emerges that displays the relative stability of
      all states, tori, and racquets. We conclude that, in marked contrast to the
      collapse of flexible polymers, the condensation of semiflexible or stiff polymers
      generically proceeds via a cascade through metastable intermediates, the
      racquets, towards a ground state, the torus or ring, as seen in the dynamical
      simulations.

PMID- 12188757
TI  - Effects of intrinsic base-pair fluctuations on charge transport in DNA.
AB  - We investigate propagation of a charge carrier along intrinsically dynamically
      disordered double-stranded DNA. This is realized by the semiclassical coupling of
      the charge with a nonlinear lattice model that can accurately describe the
      statistical mechanics of the large amplitude fluctuations of the base pairs
      leading to the thermal denaturation transition of DNA. We find that the
      fluctuating intrinsic disorder can trap the charge and inhibit polaronic charge
      transport. The dependence of the mean distance covered by the charge carrier
      until its trapping, as a function of the energy of the fluctuations of the base
      pairs is also presented.

PMID- 12188758
TI  - Thermal diffusion and chemical kinetics in laminar biomaterial due to heating by
      a free-electron laser.
AB  - We have theoretically investigated the role of thermal diffusion and chemical
      kinetics as a possible dynamic explanation for the preferential ablative
      properties of infrared radiation from a free-electron laser (FEL). The model is
      based on a laminar system composed of alternating layers of protein and saline.
      We have compared exposure to 3 microm where water is the main absorber and 6.45
      microm where both water and protein absorb. The picosecond pulses of the
      superpulse are treated as a train of impulses. We find that the heating rates are
      sufficient to superheat the outer saline layers on the nanosecond time scale,
      leading to explosive vaporization. We also find that competition between the
      layer-specific heating rates and thermal diffusion results in a wavelength
      dependent separation in layer temperatures. We consider the onset of both
      chemical bond breaking and the helix-coil transition of protein prior to
      vaporization in terms of the thermal, chemical, and structural properties of the
      system as well as laser wavelength and pulse structure. There is no evidence for
      thermal bond breaking on these time scales. At 6.45 microm, but not 3 microm,
      there is evidence for a significant helix-coil transition. While the native
      protein is ductile, the denatured protein exhibits brittle fracture. This model
      provides a dynamic mechanism to account for the preferential ablative properties
      observed with FEL radiation tuned near 6.45 microm.

PMID- 12188759
TI  - Classification of amino acids based on statistical results of known structures
      and cooperativity of protein folding.
AB  - It has been found that the 20 kinds of amino acids have different frequencies of
      occurrence in alpha,beta, and coil structures [P. Y. Chou and G. D. Fasman,
      Biochemistry 13, 211 (1974)]. Based on more known structures of proteins,
      frequencies for each amino acid in alpha and beta secondary structures are
      recalculated. Next step, under the approximation ignoring the chain connectivity
      of proteins, energy parameters to form alpha and beta secondary structures for
      each amino acid are obtained. According to the hydrophobicity and energies in
      alpha and beta secondary structures, 20 kinds of amino acids are classified. The
      results suggest that dividing amino acids to five or nine groups is desirable. At
      last, a protein model considering both two-body hydrophobic interaction and one
      body energy to form secondary structures, hydrophobic-polar alphabeta model, is
      introduced. It is shown that the consistency among various energy terms makes the
      cooperativity of protein folding closer to the experiments.

PMID- 12188760
TI  - Information space dynamics for neural networks.
AB  - We propose a coupled map lattice defined on a hypercube in M dimensions, the
      information space, to model memory retrieval by a neural network. We consider
      that both neuronal activity and the spiking phase may carry information. In this
      model the state of the network at a given time t is completely determined by a
      function y(sigma-->,t) of the bit strings sigma-->=(sigma1,sigma2,...,sigmaM),
      where sigma(i)=+/-1 with i=1,2, ...,M, that gives the intensity with which the
      information sigma--> is being expressed by the network. As an example, we
      consider logistic maps, coupled in the information space, to describe the
      evolution of the intensity function y(sigma-->,t). We propose an interpretation
      of the maps in terms of the physiological state of the neurons and the coupling
      between them, obtain Hebb-like learning rules, show that the model works as an
      associative memory, numerically investigate the capacity of the network and the
      size of the basins of attraction, and estimate finite size effects. We finally
      show that the model, when exposed to sequences of uncorrelated stimuli, shows
      recency and latency effects that depend on the noise level, delay time of
      measurement, and stimulus intensity.

PMID- 12188761
TI  - Class of self-limiting growth models in the presence of nonlinear diffusion.
AB  - The source term in a reaction-diffusion system, in general, does not involve
      explicit time dependence. A class of self-limiting growth models dealing with
      animal and tumor growth and bacterial population in a culture, on the other hand,
      are described by kinetics with explicit functions of time. We analyze a reaction
      diffusion system to study the propagation of spatial front for these models.

PMID- 12188762
TI  - Small-world view of the amino acids that play a key role in protein folding.
AB  - We use geometrical considerations to provide a different perspective on the fact
      that a few selected amino acids, the so-called "key residues," act as nucleation
      centers for protein folding. By constructing graphs corresponding to protein
      structures we show that they have the "small-world" feature of having a limited
      set of vertices with large connectivity. These vertices correspond to the key
      residues that play the role of "hubs" in the network of interactions that
      stabilize the structure of the transition state.

PMID- 12188763
TI  - Slow excitation supports propagation of slow pulses in networks of excitatory and
      inhibitory populations.
AB  - We study the propagation of traveling solitary pulses in one-dimensional networks
      of excitatory and inhibitory neurons. Each neuron is represented by the integrate
      and-fire model, and is allowed to fire only one spike. Two types of propagating
      pulses are observed. During fast pulses, inhibitory neurons fire a short time
      before or after the excitatory neurons. During slow pulses, inhibitory cells fire
      well before neighboring excitatory cells, and potentials of excitatory cells
      become negative and then positive before they fire. There is a bistable parameter
      regime in which both fast and slow pulses can propagate. Fast pulses can
      propagate at low levels of inhibition, are affected by fast excitation but are
      almost unaffected by slow excitation, and are easily elicited by stimulating
      groups of neurons. In contrast, slow pulses can propagate at intermediate levels
      of inhibition, and are difficult to evoke. They can propagate without slow
      excitation, but slow excitation makes their propagation substantially more
      robust. Fast pulses can propagate in a wider parameter regime if inhibition
      decays slowly with time, whereas slow pulses can propagate in a wider parameter
      regime if the passive time constant of inhibitory cells is large. Strong
      inhibitory-to-inhibitory conductance eliminates the slow pulses and converts the
      fast traveling pulses into irregular pulses, in which the inhibitory neurons
      segregate into two groups that have different firing delays with respect to their
      neighboring excitatory cells. In general, the velocity of the fast pulse
      increases with the axonal conductance velocity c, but there are cases in which it
      decreases with c. We suggest that the fast and slow pulses observed in our model
      correspond to the fast and slow propagating activity observed in experiments on
      neocortical slices.

PMID- 12188764
TI  - Stability of oscillatory retrieval solutions in the oscillator neural network
      without Lyapunov functions.
AB  - Constructing a Ginzburg-Landau map neural network, we analyze its storage
      capacity with an equilibrium theory of the self-consistent signal-to-noise
      analysis (SCSNA); however, the prediction does not consist with the simulation
      results just in the parameter region where the characteristic of the non-Lyapunov
      function system gets enhanced [J. Phys. A 32, 4623 (1999)]. It is expected that
      this inconsistency comes from the fact that the dynamics of retrieval and
      nonretrieval states governs the phase transition. Alternatively, we investigate
      its storage capacity with the help of the Amari-Maginu-Okada theory, a dynamical
      theory, for the stability analysis of dynamical states. We consequently found
      that the theory predicts dynamical states quite well especially in the region
      where the SCSNA breaks down, and that the phase diagram coincides quantitatively
      well with the simulation results.

PMID- 12188765
TI  - Hydration dynamics of human fingernails: an ellipsometric study.
AB  - We use spectroscopic ellipsometry to obtain the complex refractive index, n=n+ik,
      of human fingernails. By studying the change of n upon hydration and dehydration,
      we reveal three different time domains with typical time constants of 4, 150, and
      3200 min. A simple model that takes into account the presence of one fast and one
      slow process is fully consistent with the observed hydration and dehydration
      dynamics. We attribute these processes to "free" water incorporated between the
      keratin filaments and water more tightly "bound" in keratin complexes,
      respectively. From our model we determine the hydration profiles of "free" and
      "bound" water during, both, hydration and dehydration.

PMID- 12188766
TI  - Constitutive property of the local organization of leaf venation networks.
AB  - The leaf venation of dicotyledons forms complex patterns. In spite of their large
      variety of morphologies these patterns have common features. They are formed of a
      hierarchy of structures, which are connected to form a reticulum. Excellent
      images of these patterns can be obtained from leaves from which the soft tissues
      have been removed. A numerical image processing has been developed, specially
      designed for a quantitative analysis of this type of network. It provides a
      precise characterization of its geometry. The resulting data reveals a surprising
      property of reticula's nodes: the angles between vein segments are very well
      defined and it is shown that they are directly related by the radii of the
      segments. The relation between radii and angles can be expressed very simply
      using a phenomenological analogy to mechanics. This local organization principle
      is universal; all leaf venation patterns studied show the same behavior. The
      results are compared with physical networks such as fracture arrays or soap froth
      in terms of hierarchy and reorganization.

PMID- 12188767
TI  - Fokker-Planck equation for bistable potential in the optimized expansion.
AB  - The optimized expansion is used to formulate a systematic approximation scheme to
      the probability distribution of a stochastic system. The first-order
      approximation for the one-dimensional system driven by noise in an anharmonic
      potential is shown to agree well with the exact solution of the Fokker-Planck
      equation. Even for a bistable system the whole period of evolution to equilibrium
      is correctly described at various noise intensities.

PMID- 12188768
TI  - Interfacial tension and nucleation in mixtures of colloids and long ideal polymer
      coils.
AB  - Mixtures of ideal polymers with hard spheres whose diameters are smaller than the
      radius of gyration of the polymer, exhibit extensive immiscibility. The
      interfacial tension between demixed phases of these mixtures is estimated, as is
      the barrier to nucleation. The barrier is found to scale linearly with the radius
      of the polymer, causing it to become large for large polymers. Thus for large
      polymers nucleation is suppressed and phase separation proceeds via spinodal
      decomposition, as it does in polymer blends.

PMID- 12188769
TI  - Transition to ordered intercalated columns in columnar liquid crystals.
AB  - A phenomenological description of the phase transition between the disordered
      columnar phase Dhd and the ordered phase Dho is presented in which the columns
      are ordered and displaced so as to relieve the intrinsic frustration on a
      triangular lattice. A number of additional phases are predicted, including the
      one observed experimentally for the hexa-hexylthiotriphenylene columnar liquid
      crystal.

PMID- 12188770
TI  - Optimization of congested traffic by controlling stop-and-go waves.
AB  - We propose a new optimization strategy based on inducing stop-and-go waves on the
      main road and controlling their wavelength. Using numerical simulations of a
      recent stochastic car-following model we show that this strategy yields
      optimization of traffic flow when implemented in systems with a localized
      periodic inhomogeneity, such as signalized intersections and entry ramps. The
      optimization process is explained by our finding of a generalized fundamental
      diagram (GFD) for traffic, namely a flux-density-wavelength relation. Projecting
      the GFD on the density-flux plane yields a two-dimensional region of stable
      states, qualitatively similar to that found empirically [Kerner, Phys. Rev. Lett.
      81, 3797 (1998)] in synchronized traffic.

PMID- 12188771
TI  - Topology of the conceptual network of language.
AB  - We define two words in a language to be connected if they express similar
      concepts. The network of connections among the many thousands of words that make
      up a language is important not only for the study of the structure and evolution
      of languages, but also for cognitive science. We study this issue quantitatively,
      by mapping out the conceptual network of the English language, with the
      connections being defined by the entries in a Thesaurus dictionary. We find that
      this network presents a small-world structure, with an amazingly small average
      shortest path, and appears to exhibit an asymptotic scale-free feature with
      algebraic connectivity distribution.

PMID- 12188772
TI  - Evidence for "fragile" glass-forming behavior in the relaxation of Coulomb
      frustrated three-dimensional systems.
AB  - We show by means of a Monte Carlo simulation study that three-dimensional models
      with long-range frustration display the generic phenomena seen in fragile glass
      forming liquids. Due to their properties (absence of quenched disorder, physical
      motivation in terms of structural frustration, and tunable fragility), these
      systems appear as promising minimal theoretical models for describing the glass
      transition of supercooled liquids.

PMID- 12188773
TI  - Critical exponents and percolation thresholds in two-dimensional systems with a
      finite interplane coupling.
AB  - Classical site percolation was used to study numerically the effect of interplane
      coupling in the range 10(-1)-10(-6) of the in-plane coupling on the static
      correlation length exponent nu and the critical dimension D. It was found that
      even for the smallest coupling values the exponents take their three-dimensional
      (3D) values for sufficiently large system sizes. The percolation threshold p(c),
      however, varies continuously from the 2D to the 3D value with a power-law
      exponent kappa=0.41(2), which, to within error, is the same for simple cubic,
      bcc, and fcc lattices. As predicted by renormalization-group theory this exponent
      equals the inverse of the susceptibility exponent gamma=43/18.

PMID- 12188774
TI  - Cusp-scaling behavior in fractal dimension of chaotic scattering.
AB  - A topological bifurcation in chaotic scattering is characterized by a sudden
      change in the topology of the infinite set of unstable periodic orbits embedded
      in the underlying chaotic invariant set. We uncover a scaling law for the fractal
      dimension of the chaotic set for such a bifurcation. Our analysis and numerical
      computations in both two- and three-degrees-of-freedom systems suggest a striking
      feature associated with these subtle bifurcations: the dimension typically
      exhibits a sharp, cusplike local minimum at the bifurcation.

PMID- 12188775
TI  - Internal modes of sine-Gordon solitons in the presence of spatiotemporal
      perturbations.
AB  - We investigate the dynamics of the sine-Gordon solitons perturbed by
      spatiotemporal external forces. We prove the existence of internal (shape) modes
      of sine-Gordon solitons when they are in the presence of inhomogeneous space
      dependent external forces, provided some conditions (for these forces) hold.
      Additional periodic time-dependent forces can sustain oscillations of the soliton
      width. We show that, in some cases, the internal mode even can become unstable,
      causing the soliton to decay into an antisoliton and two solitons. In general, in
      the presence of spatiotemporal forces the soliton behaves as a deformable
      (nonrigid) object. A soliton moving in an array of inhomogeneities can also
      present sustained oscillations of its width. There are very important phenomena
      (like the soliton-antisoliton collisions) where the existence of internal modes
      plays a crucial role.

PMID- 12188776
TI  - Feedback stabilization of unstable propagating waves.
AB  - Propagating wave segments are stabilized to a constant size and shape by applying
      negative feedback from the measured wave area to the excitability of the medium.
      The locus of steady-state wave size as a function of excitability defines the
      perturbation threshold for the initiation of spiral waves. This locus also
      defines the excitability boundary for spiral wave behavior in active media.

PMID- 12188777
TI  - Numerical study of a first-order irreversible phase transition in a CO+NO
      catalyzed reaction model.
AB  - The first-order irreversible phase transition (IPT) of the Yaldran-Khan model
      [Yaldran-Khan, J. Catal. 131, 369 (1991)] for the CO+NO reaction is studied using
      the constant-coverage (CC) ensemble and performing epidemic simulations. The CC
      method allows the study of hysteretic effects close to coexistence as well as the
      location of both the upper spinodal point and the coexistence point. Epidemic
      studies show that at coexistence the number of active sites decreases according
      to a (short-time) power law followed by a (long-time) exponential decay. It is
      concluded that first-order IPT's share many characteristics of their reversible
      counterparts, such as the development of short-ranged correlations, hysteretic
      effects, metastabilities, etc.

PMID- 12188778
TI  - Dynamical random graphs with memory.
AB  - We study the large-time dynamics of a Markov process whose states are finite but
      unbounded graphs. The number of vertices is described by a supercritical
      branching process, and the edges follow a certain mean-field dynamics determined
      by the rates of appending and deleting: the older an edge is, the lesser is the
      probability that it is still in the graph. The lifetime of any edge is
      distributed exponentially. We call its mean value (common for all edges) a
      parameter of memory, since it shows for how long the system keeps a particular
      connection between the vertices in the graph. We show that our model provides a
      bridge between two well-known models: when the parameter of memory goes to
      infinity this is a generalized model of random growth, and when this parameter is
      zero, i.e., no memory, our model behaves as a random graph. Thus by introducing a
      general class of dynamical graphs we have a unified overview on rather different
      models and the relations between them. We find all the critical values of the
      parameters at which our model exhibits phase transitions and describe the
      properties of the phase diagram. Finally, we compare and discuss the efficiency
      of the corresponding networks.

PMID- 12188779
TI  - Critical behavior of semi-infinite random systems at the special surface
      transition.
AB  - We use a three-dimensional massive field theory up to the two-loop approximation
      to study the critical behavior of semi-infinite quenched random Ising-like
      systems at the special surface transition. Besides, we extend up to the next-to
      leading order, the previous first-order results of the sqrt[epsilon] expansion
      obtained by Ohno and Okabe [Phys. Rev. B 46, 5917 (1992)]. The numerical
      estimates for surface critical exponents in both cases are computed by means of
      the Pade analysis. Moreover, in the case of the massive field theory we perform
      Pade-Borel resummation of the resulting two-loop series expansions for surface
      critical exponents. The most reliable estimates for critical exponents of semi
      infinite systems with quenched bulk randomness at the special surface transition,
      which we can obtain in the frames of the present approximation scheme, are
      eta(//)=-0.238, Delta(1)=1.098, eta( perpendicular )=-0.104, beta(1)=0.258,
      gamma(11)=0.839, gamma(1)=1.426, delta(1)=6.521, and delta(11)=4.249. These
      values are different from critical exponents for pure semi-infinite Ising-like
      systems and show that in a system with quenched bulk randomness the plane
      boundary is characterized by a new set of critical exponents at the special
      surface transition.

PMID- 12188780
TI  - Statistical mechanics of two hard disks in a rectangular box.
AB  - A system of two hard disks in a rectangular box is studied based on the exact
      partition function and equilibrium distribution functions of particles. Box-size
      dependence of some quantities of interest, such as pressure and the particle
      distribution functions, is investigated and in particular the negative
      compressibility of the van der Waals type and the corresponding phase transition
      are analyzed in detail. This system turns out to have rich structures that are
      related to the ergode-nonergode transitions in this system.

PMID- 12188781
TI  - Fractal behavior of the shortest path between two lines in percolation systems.
AB  - Using Monte Carlo simulations, we determine the scaling form for the probability
      distribution of the shortest path l between two lines in a three-dimensional
      percolation system at criticality; the two lines can have arbitrary positions,
      orientations, and lengths. We find that the probability distributions can exhibit
      up to four distinct power-law regimes (separated by crossover regimes) with
      exponents depending on the relative orientations of the lines. We explain this
      rich fractal behavior with scaling arguments.

PMID- 12188782
TI  - First-order transition in a particle deposition-evaporation model.
AB  - We introduce a simple stochastic growth model where particles of two different
      species are deposited and evaporated. In the model, a randomly chosen particle of
      two species is deposited at a rate p and a particle on the edge of the plateau of
      the interface is evaporated at a rate 1-p. When p<p(c1)=0.4985(2) and
      p>p(c2)=0.5015(5), the velocity of the interface is zero. When p(c1)</=p</=p(c2),
      however, the interface grows with a constant velocity. At both p(c1) and p(c2),
      the velocity of the interface changes from zero to a constant value
      discontinuously. The first-order transitions in our model are related to a
      nonequilibrium phase transition from an active to an inactive phase at the bottom
      layer of the interface. Interestingly, the first-order transition at p(c1) is
      triggered by the combination of the parity conserving and the directed
      percolation dynamics. We explain why the transitions in our model are of first
      order. Moreover, our model shows two nonequilibrium roughening transitions at
      p(c1) as well as at p(r)[=0.444(2)].

PMID- 12188783
TI  - Excitability transitions and wave dynamics under spatiotemporal structured noise.
AB  - We present an analytic and numerical study of the effects of external
      fluctuations in active media. Our analytical methodology transforms the initial
      stochastic partial differential equations into an effective set of deterministic
      reaction-diffusion equations. As a result we are able to explain and make
      quantitative predictions on the systematic and constructive effects of the noise,
      for example, target patterns created out of noise and traveling or spiral waves
      sustained by noise. Our study includes the case of realistic noises with temporal
      and spatial structures.

PMID- 12188784
TI  - Jamming transitions and avalanches in the game of Dots-and-Boxes.
AB  - We study the game of Dots-and-Boxes from a statistical point of view. The early
      game can be treated as a case of random sequential adsorption, with a jamming
      transition that marks the beginning of the end game. We derive a set of
      differential equations to make predictions about the state of the lattice at the
      transition, and thus about the distribution of avalanches in the end game.

PMID- 12188785
TI  - Vertex overload breakdown in evolving networks.
AB  - We study evolving networks based on the Barabasi-Albert scale-free network model
      with vertices sensitive to overload breakdown. The load of a vertex is defined as
      the betweenness centrality of the vertex. Two cases of load limitation are
      considered, corresponding to the fact that the average number of connections per
      vertex is increasing with the network's size ("extrinsic communication
      activity"), or that it is constant ("intrinsic communication activity").
      Avalanchelike breakdowns for both load limitations are observed. In order to
      avoid such avalanches we argue that the capacity of the vertices has to grow with
      the size of the system. An interesting irregular dynamics of the formation of the
      giant component (for the intrinsic communication activity case) is also studied.
      Implications on the growth of the Internet are discussed.

PMID- 12188786
TI  - Ising model in small-world networks.
AB  - The Ising model in small-world networks generated from two- and three-dimensional
      regular lattices has been studied. Monte Carlo simulations were carried out to
      characterize the ferromagnetic transition appearing in these systems. In the
      thermodynamic limit, the phase transition has a mean-field character for any
      finite value of the rewiring probability p, which measures the disorder strength
      of a given network. For small values of p, both the transition temperature and
      critical energy change with p as a power law. In the limit p-->0, the heat
      capacity at the transition temperature diverges logarithmically in two
      dimensional (2D) networks and as a power law in 3D.

PMID- 12188787
TI  - Generalized contact process on random environments.
AB  - Spreading from a seed is studied by Monte Carlo simulation on a square lattice
      with two types of sites affecting the rates of birth and death. These systems
      exhibit a critical transition between survival and extinction. For time-dependent
      background, this transition is equivalent to those found in homogeneous systems
      (i.e., to directed percolation). For frozen backgrounds, the appearance of the
      Griffiths phase prevents the accurate analysis of this transition. For long times
      in the subcritical region, the spreading remains localized in compact (rather
      than ramified) patches, and the average number of occupied sites increases
      logarithmically in the surviving trials.

PMID- 12188788
TI  - Kinetics in one-dimensional lattice gas and Ising models from time-dependent
      density-functional theory.
AB  - Time-dependent density-functional theory, proposed recently in the context of
      atomic diffusion and nonequilibrium processes in solids, is tested against Monte
      Carlo simulation. In order to assess the basic approximation of that theory, the
      representation of nonequilibrium states by a local equilibrium distribution
      function, we focus on one-dimensional lattice models, where all equilibrium
      properties can be worked exactly from the known free energy as a functional of
      the density. This functional determines the thermodynamic driving forces away
      from equilibrium. In our studies of the interfacial kinetics of atomic hopping
      and spin relaxation, we find excellent agreement with simulations, suggesting
      that the method is also useful for treating more complex problems.

PMID- 12188789
TI  - Hierarchical reference theory study of the lattice restricted primitive model.
AB  - A three dimensional model of point charges, named lattice restricted primitive
      model (LRPM), is investigated by using the hierachical reference theory of
      fluids. This approach, which generalizes the momentum renormalization group
      technique, is shown to capture the physics of the model and provides a
      quantitative description of the phase diagram. The comparison with recent
      numerical simulations and with other theoretical approaches is discussed both for
      the LRPM and for the Blume-Capel model, which can be seen as a screened version
      of LRPM. The nonuniversal crossover region close to the tricritical point is also
      discussed.

PMID- 12188790
TI  - Universality of the off-equilibrium response function in the kinetic Ising chain.
AB  - The off-equilibrium response function chi(t,t(w)) and autocorrelation function
      C(t,t(w)) of an Ising chain with spin-exchange dynamics are studied numerically
      and compared with the same quantities in the case of spin-flip dynamics. It is
      found that, even though these quantities are different in the two cases, the
      parametric plot of chi(t,t(w)) versus C(t,t(w)) is the same. While this result
      could be expected in higher dimensionality, where chi(C) is related to the
      equilibrium state, it is far from trivial in the one-dimensional case where this
      relation does not hold. The origin of the universality of chi(C) is traced back
      to the optimization of domains position with respect to the perturbing external
      field. This mechanism is investigated resorting to models with a single domain
      moving in a random environment.

PMID- 12188791
TI  - Scale-free network model of node and connection diversity.
AB  - A network model with node and connection diversity is proposed in this paper.
      Distinctly from to other models whose nodes and connections are represented by
      identical simple points and lines, we investigate inhomogeneous networks with two
      kinds of sites and link by growth of preferential attachment. Scale-free networks
      with varied centralizations and exponents (ranging from 2.0 to theoretically
      infinity) are obtained, and the influences of the relative ratio of the two kinds
      of sites p, the number of links connected from each site m, and initial
      attractiveness delta are studied. A mean-field theory that agrees well with our
      numerical results was proposed and analyzed. The theory gives the analytical
      scaling exponent of the form gamma=2+p+delta/m-delta(1-p)/(mp+m+delta).

PMID- 12188792
TI  - Extrapolation and the Bulirsch-Stoer algorithm.
AB  - The Bulirsch-Stoer extrapolation algorithm was used in a statistical mechanics
      setting in 1984 by Henkel and Patkos. Since then it has been used numerous times
      in a large variety of settings to extrapolate from finite size systems to the
      infinite system in a large variety of situations in statistical mechanics. We
      investigate some of its characteristics by using it in situations where the
      behavior of the infinite system is known. One characteristic is the error
      involved with the algorithm. More importantly we investigate the dependence of
      the effectiveness of the algorithm on the size and number of systems used as
      input and find that a larger number of smaller systems results in better results
      than a few much larger systems.

PMID- 12188793
TI  - Role of pointlike topological excitations at criticality: From vortices to global
      monopoles.
AB  - We determine the detailed thermodynamic behavior of vortices in the O(2) scalar
      model in two dimensions (2D) and of global monopoles in the O(3) model in 3D. We
      construct numerical techniques, based on cluster decomposition algorithms, to
      analyze the point defect configurations. We find that these criteria produce
      results for the Kosterlitz-Thouless temperature in agreement with a topological
      transition between a polarizable insulator and a conductor, at which free
      topological charges appear in the system. For global monopoles we find no pair
      unbinding transition. Instead a transition to a dense state where pairs are no
      longer distinguishable occurs at T<T(c), without leading to long-range disorder.
      We produce both extensive numerical evidence of this behavior as well as a
      semianalytic treatment of the partition function for defects. General
      expectations for N=D>3 are drawn, based on the observed behavior.

PMID- 12188794
TI  - Nonextensive entropies derived from form invariance of pseudoadditivity.
AB  - The form invariance of pseudoadditivity is shown to determine the structure of
      nonextensive entropies. Nonextensive entropy is defined as the appropriate
      expectation value of nonextensive information content, similar to the definition
      of Shannon entropy. Information content in a nonextensive system is obtained
      uniquely from generalized axioms by replacing the usual additivity with
      pseudoadditivity. The satisfaction of the form invariance of the pseudoadditivity
      of nonextensive entropy and its information content is found to require the
      normalization of nonextensive entropies. The proposed principle requires the same
      normalization as that derived previously [A.K. Rajagopal and S. Abe, Phys. Rev.
      Lett. 83, 1711 (1999)], but is simpler and establishes a basis for the systematic
      definition of various entropies in nonextensive systems.

PMID- 12188795
TI  - Resistance and resistance fluctuations in random resistor networks under biased
      percolation.
AB  - We consider a two-dimensional random resistor network (RRN) in the presence of
      two competing biased processes consisting of the breaking and recovering of
      elementary resistors. These two processes are driven by the joint effects of an
      electrical bias and of the heat exchange with a thermal bath. The electrical bias
      is set up by applying a constant voltage or, alternatively, a constant current.
      Monte Carlo simulations are performed to analyze the network evolution in the
      full range of bias values. Depending on the bias strength, electrical failure or
      steady state are achieved. Here we investigate the steady state of the RRN
      focusing on the properties of the non-Ohmic regime. In constant-voltage
      conditions, a scaling relation is found between <R>/<R>(0) and V/V(0), where <R>
      is the average network resistance, <R>(0) the linear regime resistance, and V0
      the threshold value for the onset of nonlinearity. A similar relation is found in
      constant-current conditions. The relative variance of resistance fluctuations
      also exhibits a strong nonlinearity whose properties are investigated. The power
      spectral density of resistance fluctuations presents a Lorentzian spectrum and
      the amplitude of fluctuations shows a significant non-Gaussian behavior in the
      prebreakdown region. These results compare well with electrical breakdown
      measurements in thin films of composites and of other conducting materials.

PMID- 12188796
TI  - Aging in ferromagnetic systems at criticality near four dimensions.
AB  - We study the off-equilibrium response and correlation functions and the
      corresponding fluctuation-dissipation ratio for a purely dissipative relaxation
      of an O(N) symmetric vector model (model A) below its upper critical dimension.
      The scaling behavior of these quantities is analyzed and the associated universal
      functions are determined at first order in epsilon=4-d in the high-temperature
      phase and at criticality. A nontrivial limit of the fluctuation-dissipation ratio
      is found in the aging regime X( infinity )=1/2(1
      (epsilon/4)(N+2)/(N+8))+O(epsilon(2)).

PMID- 12188797
TI  - Dielectric breakdown model at small eta: pole dynamics.
AB  - We consider the dielectric breakdown model in the limit eta-->0(+). This is shown
      to lead to Sivashinsky's equation. We show that a particular configuration of
      poles is linearly stable, in analogy to the stability of the 1/2 finger for
      diffusion limited aggregation, and compute exactly the eigenvalues of the
      stability matrix.

PMID- 12188798
TI  - Pseudofractal scale-free web.
AB  - We find that scale-free random networks are excellently modeled by simple
      deterministic graphs. Our graph has a discrete degree distribution (degree is the
      number of connections of a vertex), which is characterized by a power law with
      exponent gamma=1+ln 3/ln 2. Properties of this compact structure are surprisingly
      close to those of growing random scale-free networks with gamma in the most
      interesting region, between 2 and 3. We succeed to find exactly and numerically
      with high precision all main characteristics of the graph. In particular, we
      obtain the exact shortest-path-length distribution. For a large network (ln N>>1)
      the distribution tends to a Gaussian of width approximately sqrt[ln N] centered
      at (-)l approximately ln N. We show that the eigenvalue spectrum of the adjacency
      matrix of the graph has a power-law tail with exponent 2+gamma.

PMID- 12188799
TI  - Spin dephasing in the extended strong collision approximation.
AB  - For Markovian dynamics of field fluctuations we present here an extended strong
      collision approximation, thereby putting our previous strong collision approach
      [Phys. Rev. Lett. 83, 4215 (1999)]) into a systematic framework. Our approach
      provides expressions for the free induction and spin-echo magnetization decays
      that may be solved analytically or at least numerically. It is tested for the
      generic cases of dephasing due to an Anderson-Weiss process and due to restricted
      diffusion in a linear field gradient.

PMID- 12188800
TI  - Evolution and structure formation of the distribution of partition function
      zeros: triangular type Ising lattices with cell decoration.
AB  - The distribution of partition function zeros of the two-dimensional Ising model
      in the complex temperature plane is studied within the context of triangular
      decorated lattices and their triangle-star transformations. Exact recursion
      relations for the zeros are deduced for the description of the evolution of the
      distribution of the zeros subject to the change of decoration level. In the limit
      of infinite decoration level, the decorated lattices essentially possess the
      Sierpinski gasket or its triangle-star transformation as the inherent structure.
      The positions of the zeros for the infinite decorated lattices are shown to
      coincide with the ones for the Sierpinski gasket or its triangle-star
      transformation, and the distributions of zeros all appear to be a union of
      infinite scattered points and a Jordan curve, which is the limit of the scattered
      points.

PMID- 12188801
TI  - Probabilistic description of traffic breakdowns.
AB  - We analyze the characteristic features of traffic breakdown. To describe this
      phenomenon we apply the probabilistic model regarding the jam emergence as the
      formation of a large car cluster on a highway. In these terms, the breakdown
      occurs through the formation of a certain critical nucleus in the metastable
      vehicle flow, which enables us to confine ourselves to one cluster model. We
      assume that, first, the growth of the car cluster is governed by attachment of
      cars to the cluster whose rate is mainly determined by the mean headway distance
      between the car in the vehicle flow and, maybe, also by the headway distance in
      the cluster. Second, the cluster dissolution is determined by the car escape from
      the cluster whose rate depends on the cluster size directly. The latter is
      justified using the available experimental data for the correlation properties of
      the synchronized mode. We write the appropriate master equation converted then
      into the Fokker-Planck equation for the cluster distribution function and analyze
      the formation of the critical car cluster due to the climb over a certain
      potential barrier. The further cluster growth irreversibly causes jam formation.
      Numerical estimates of the obtained characteristics and the experimental data of
      the traffic breakdown are compared. In particular, we draw a conclusion that the
      characteristic intrinsic time scale of the breakdown phenomenon should be about 1
      min and explain the case why the traffic volume interval inside which traffic
      breakdown is observed is sufficiently wide.

PMID- 12188803
TI  - 25th-order high-temperature expansion results for three-dimensional Ising-like
      systems on the simple-cubic lattice.
AB  - 25th-order high-temperature series are computed for a general nearest-neighbor
      three-dimensional Ising model with arbitrary potential on the simple cubic
      lattice. In particular, we consider three improved potentials characterized by
      suppressed leading scaling corrections. Critical exponents are extracted from
      high-temperature series specialized to improved potentials, obtaining
      gamma=1.2373(2), nu=0.63012(16), alpha=0.1096(5), eta=0.036 39(15), beta=0.326
      53(10), and delta=4.78 93(8). Moreover, biased analyses of the 25th-order series
      of the standard Ising model provide the estimate Delta=0.52(3) for the exponent
      associated with the leading scaling corrections. By the same technique, we study
      the small-magnetization expansion of the Helmholtz free energy. The results are
      then applied to the construction of parametric representations of the critical
      equation of state, using a systematic approach based on a global stationarity
      condition. Accurate estimates of several universal amplitude ratios are also
      presented.

PMID- 12188802
TI  - Random matrix approach to cross correlations in financial data.
AB  - We analyze cross correlations between price fluctuations of different stocks
      using methods of random matrix theory (RMT). Using two large databases, we
      calculate cross-correlation matrices C of returns constructed from (i) 30-min
      returns of 1000 US stocks for the 2-yr period 1994-1995, (ii) 30-min returns of
      881 US stocks for the 2-yr period 1996-1997, and (iii) 1-day returns of 422 US
      stocks for the 35-yr period 1962-1996. We test the statistics of the eigenvalues
      lambda(i) of C against a "null hypothesis"--a random correlation matrix
      constructed from mutually uncorrelated time series. We find that a majority of
      the eigenvalues of C fall within the RMT bounds [lambda(-),lambda(+)] for the
      eigenvalues of random correlation matrices. We test the eigenvalues of C within
      the RMT bound for universal properties of random matrices and find good agreement
      with the results for the Gaussian orthogonal ensemble of random matrices-implying
      a large degree of randomness in the measured cross-correlation coefficients.
      Further, we find that the distribution of eigenvector components for the
      eigenvectors corresponding to the eigenvalues outside the RMT bound display
      systematic deviations from the RMT prediction. In addition, we find that these
      "deviating eigenvectors" are stable in time. We analyze the components of the
      deviating eigenvectors and find that the largest eigenvalue corresponds to an
      influence common to all stocks. Our analysis of the remaining deviating
      eigenvectors shows distinct groups, whose identities correspond to conventionally
      identified business sectors. Finally, we discuss applications to the construction
      of portfolios of stocks that have a stable ratio of risk to return.

PMID- 12188804
TI  - Variational perturbation theory for Markov processes.
AB  - We develop a convergent variational perturbation theory for conditional
      probability densities of Markov processes. The power of the theory is illustrated
      by applying it to the diffusion of a particle in an anharmonic potential.

PMID- 12188805
TI  - Localization of thermal packets and metastable states in the Sinai model.
AB  - We consider the Sinai model describing a particle diffusing in a one-dimensional
      random force field. As shown by Golosov, this model exhibits a strong
      localization phenomenon for the thermal packet: all thermal trajectories starting
      from the same initial condition in the same sample remain within a finite
      distance of each other even in the limit of infinite time. More precisely, he has
      proved that the disorder average P(t)(y) of the distribution of the relative
      distance y=x(t)-m(t) with respect to the (disorder-dependent) most probable
      position m(t), converges in the limit t--> infinity, towards a distribution
      P(G)(y) defined as a functional of two independent Bessel processes. In this
      paper, we revisit this question of the localization of the thermal packet. We
      first generalize the result of Golosov by computing explicitly the joint
      distribution P( infinity )(y,u) of relative position y=x(t)-m(t) and relative
      energy u=U(x(t))-U(m(t)) for the thermal packet. Next, we compute the
      localization parameters Y(k), representing the disorder-averaged probabilities
      that k particles of the thermal packet are at the same place in the infinite-time
      limit, and the correlation function C(l) representing the disorder-averaged
      probability density that two particles of the thermal packet are at a distance l
      from each other. We, moreover, prove that our results for Y(k) and C(l) exactly
      coincide with the thermodynamic limit L--> infinity of the analog quantities
      computed for independent particles at equilibrium in a finite sample of length L.
      So even if the Sinai dynamics on the infinite line is always out-of-equilibrium
      since it consists in jumps in deeper and deeper wells, the particles of the same
      thermal packet can nevertheless be considered asymptotically as if they were at
      thermal equilibrium in a Brownian potential. Finally, we discuss the properties
      of the finite-time metastable states that are responsible for the localization
      phenomenon and compare with the general theory of metastable states in glassy
      systems, in particular as a test of the Edwards conjecture.

PMID- 12188806
TI  - Large-scale topological and dynamical properties of the Internet.
AB  - We study the large-scale topological and dynamical properties of real Internet
      maps at the autonomous system level, collected in a 3-yr time interval. We find
      that the connectivity structure of the Internet presents statistical
      distributions settled in a well-defined stationary state. The large-scale
      properties are characterized by a scale-free topology consistent with previous
      observations. Correlation functions and clustering coefficients exhibit a
      remarkable structure due to the underlying hierarchical organization of the
      Internet. The study of the Internet time evolution shows a growth dynamics with
      aging features typical of recently proposed growing network models. We compare
      the properties of growing network models with the present real Internet data
      analysis.

PMID- 12188807
TI  - Fragility of the free-energy landscape of a directed polymer in random media.
AB  - We examine the sensitiveness of the free-energy landscape of a directed polymer
      in random media with respect to various kinds of infinitesimally weak
      perturbation including the intriguing case of temperature chaos. To this end, we
      combine the replica Bethe Ansatz approach outlined by Sales and Yoshino (e-print
      cond-mat/0112384), the mapping to a modified Sinai model, and numerically exact
      calculations by the transfer-matrix method. Our results imply that for all the
      perturbations under study there is a slow crossover from a weakly perturbed
      regime, where rare events take place, to a strongly perturbed regime at larger
      length scales beyond the so-called overlap length, where typical events take
      place leading to chaos, i.e., a complete reshuffling of the free-energy
      landscape. Within the replica space, the evidence for chaos is found in the
      factorization of the replicated partition function induced by infinitesimal
      perturbations. This is the reflex of explicit replica-symmetry breaking.

PMID- 12188808
TI  - Classical-to-critical crossovers from field theory.
AB  - We extend our previous determinations of nonasymptotic critical behavior of Phys.
      Rev. B 32, 7209 (1985) and 35, 3585 (1987) to accurate expressions of the
      complete classical-to-critical crossover (in three-dimensional field theory) in
      terms of the temperaturelike scaling field (i.e., along the critical isochore)
      for (1) the correlation length, the susceptibility, and the specific heat in the
      homogeneous phase for the n-vector model (n=1 to 3) and (2) the spontaneous
      magnetization (coexistence curve), the susceptibility, and the specific heat in
      the inhomogeneous phase for the Ising model (n=1). The present calculations
      include the seventh-loop order of Murray and Nickel and closely account for the
      up-to-date estimates of universal asymptotic critical quantities (exponents and
      amplitude combinations) provided by Guida and Zinn-Justin [J. Phys. A 31, 8103
      (1998)].

PMID- 12188809
TI  - Characteristic features of symmetry breaking in two-component Bose-Einstein
      condensates.
AB  - We examine the stability properties of the ground state of two-component Bose
      Einstein condensates as a function of the interspecies interactions. A stability
      criterion is identified from the curvature matrix of the Gross-Pitaevskii energy
      functional subject to the normalization conditions. By analyzing the stability
      signature, the characteristic features of the spontaneous spatial symmetry
      breaking are verified in various types of traps. The details of the differences
      between the continuous symmetry breaking and discrete symmetry breaking are
      discussed.

PMID- 12188810
TI  - Investigation of the quantum cantori regime in quarter-stadium billiards.
AB  - We study experimentally and numerically the regime of quantum cantori in quarter
      stadium billiards. Experimentally, a quarter-stadium billiard is simulated by a
      thin quarter-stadium microwave cavity. Using a field perturbation technique and a
      circular wave expansion method we reconstruct the eigenfunctions of the quarter
      stadium microwave billiard with the parameter epsilon =0.1 in the cantori regime
      N=7-63. The quarter-stadium billiards with epsilon =0.1 and 0.05, respectively,
      are also investigated numerically. We show that in the quantum cantori regime the
      rescaled localization length of the eigenfunctions fluctuates around a value that
      depends on the parameter epsilon.

PMID- 12188811
TI  - Chaos and the continuum limit in the gravitational N-body problem. II.
      Nonintegrable potentials.
AB  - This paper continues a numerical investigation of the statistical properties of
      "frozen-N orbits," i.e., orbits evolved in frozen, time-independent N-body
      realizations of smooth density distributions rho corresponding to both integrable
      and nonintegrable potentials, allowing for 10(2.5)</=N</=10(5.5). The focus is on
      distinguishing between, and quantifying, the effects of graininess on initial
      conditions corresponding, in the continuum limit, to regular and chaotic orbits.
      Ordinary Lyapunov exponents chi do not provide a useful diagnostic for
      distinguishing between regular and chaotic behavior. Frozen-N orbits
      corresponding in the continuum limit to both regular and chaotic characteristics
      have large positive chi even though, for large N, the "regular" frozen-N orbits
      closely resemble regular characteristics in the smooth potential. Alternatively,
      viewed macroscopically, both regular and "chaotic" frozen-N orbits diverge as a
      power law in time from smooth orbits with the same initial condition. However,
      convergence towards the continuum limit is much slower for chaotic orbits. For
      regular orbits, the time scale associated with this divergence t(G) approximately
      N(1/2)t(D), with t(D) a characteristic dynamical, or crossing, time; for chaotic
      orbits t(G) approximately (ln N)t(D). For N>10(3)-10(4), clear distinctions exist
      between the phase mixing of initially localized ensembles, which, in the
      continuum limit, exhibit regular versus chaotic behavior. Regular ensembles
      evolved in a frozen-N density distribution diverge as a power law in time, albeit
      more rapidly than ensembles evolved in the smooth distribution. Chaotic ensembles
      diverge in a fashion that is roughly exponential, albeit at a larger rate than
      that associated with the exponential divergence of the same ensemble evolved in
      smooth rho. For both regular and chaotic ensembles, finite-N effects are well
      mimicked, both qualitatively and quantitatively, by energy-conserving white noise
      with amplitude eta proportional, variant 1/N. This suggests strongly that earlier
      investigations of the effects of low amplitude noise on phase space transport in
      smooth potentials are directly relevant to real physical systems.

PMID- 12188812
TI  - Tailoring the profile and interactions of optical localized structures.
AB  - We experimentally demonstrate the broad tunability of the main features of
      optical localized structures (LS's) in a nonlinear interferometer. By discussing
      how a single LS depends on the system spatial frequency bandwidth, we show that a
      modification of its tail leads to the possibility of tuning the interactions
      between LS pairs, and thus the equilibrium distances at which LS bound states
      form. This is in agreement with a general theoretical model describing weak
      interactions of LS in nonlinear dissipative systems.

PMID- 12188814
TI  - Empirical bifurcation analysis of optical pattern formation.
AB  - The experimental characterization of pattern forming bifurcations is difficult,
      since the unstable solutions are generally not accessible in experiments. In
      nonlinear optics, a novel control scheme allows one to select and stabilize
      generic patterns and thus to track these solutions in parameter space. This
      Fourier space scheme is applied to a single-feedback system and the amplitudes of
      roll, square and hexagon patterns are determined experimentally. Even though the
      bifurcation is imperfect, the coefficients of a prototype amplitude equation are
      recovered. The coefficients show satisfactory agreement with theory and with
      numerical simulations, which are performed for comparison. The simulations also
      clarify the origin of the imperfect bifurcation in the experiment: boundaries and
      speckles appear to have an unexpected strong influence.

PMID- 12188813
TI  - Quantum-classical correspondence in perturbed chaotic systems.
AB  - We discuss the behavior of fidelity for a classically chaotic quantum system. We
      show the existence of a critical value of the perturbation above which the
      quantum decay, exponential or power law, follows the classical one. The
      independence of the decay rate of the perturbation strength, discussed in the
      literature, is a consequence of the quantum-classical correspondence of the
      relaxation process.

PMID- 12188815
TI  - Localization in band random matrix models with and without increasing diagonal
      elements.
AB  - It is shown that localization of eigenfunctions in the Wigner band random matrix
      model with increasing diagonal elements can be related to localization in a band
      random matrix model with random diagonal elements. The relation is obtained by
      making use of a result of a generalization of Brillouin-Wigner perturbation
      theory, which shows that reduced Hamiltonian matrices with relatively small
      dimensions can be introduced for nonperturbative parts of eigenfunctions, and by
      employing intermediate basis states, which can improve the method of the reduced
      Hamiltonian matrix. The latter model deviates from the standard band random
      matrix model mainly in two aspects: (i) the root mean square of diagonal elements
      is larger than that of off-diagonal elements within the band, and (ii)
      statistical distributions of the matrix elements are close to the Levy
      distribution in their central parts, except in the high top regions.

PMID- 12188816
TI  - Current and vortex statistics in microwave billiards.
AB  - Using the one-to-one correspondence between the Poynting vector in a microwave
      billiard and the probability current density in the corresponding quantum system,
      probability densities and currents were studied in a microwave billiard with a
      ferrite insert as well as in an open billiard. Distribution functions were
      obtained for probability densities, currents, and vorticities. In addition, the
      vortex pair correlation function could be extracted. For all studied quantities a
      complete agreement with the predictions from the approach using a random
      superposition of plane waves was obtained.

PMID- 12188817
TI  - Torus fractalization and intermittency.
AB  - The bifurcation transition is studied for the onset of intermittency analogous to
      the Pomeau-Manneville mechanism of type I, but generalized for the presence of a
      quasiperiodic external force. The analysis is concentrated on the torus
      fractalization (TF) critical point that occurs at some critical amplitude of
      driving. (At smaller amplitudes the bifurcation corresponds to a collision and
      subsequent disappearance of two smooth invariant curves, and at larger amplitudes
      it is a touch of attractor and repeller at some fractal set without coincidence.)
      For the TF critical point, renormalization group (RG) analysis is developed. For
      the golden mean rotation number a nontrivial fixed-point solution of the RG
      equation is found in a class of fractional-linear functions with coefficients
      depending on the phase variable. Universal constants are computed that are
      responsible for scaling in phase space (alpha=2.890 053... and beta= -1.618
      034...) and in parameter space (delta(1)=3.134 272... and delta(2)=1.618 034...).
      An analogy with the Harper equation is outlined, which reveals important
      peculiarities of the transition. For amplitudes of driving less than the critical
      value the transition leads (in the presence of an appropriate reinjection
      mechanism) to intermittent chaotic regimes; in the supercritical case it gives
      rise to a strange nonchaotic attractor.

PMID- 12188818
TI  - Multioscillatory patterns in a hybrid semiconductor gas-discharge system.
AB  - A planar pattern forming semiconductor gas-discharge device is examined. While
      being driven with a stationary voltage, it generates patterns that contain
      domains oscillating with different frequencies. The multioscillatory pattern is
      formed in a sequence of bifurcations from the homogeneous stationary state. A
      nonlinear interaction between different parts of the pattern can be detected. It
      is suggested that the observed behavior is due to the coupling of processes in
      two nonlinear components, the gas-discharge gap and the semiconductor cathode
      fabricated from high resistance gallium arsenide.

PMID- 12188819
TI  - Effective Hamiltonian for a microwave billiard with attached waveguide.
AB  - In a recent work the resonance widths in a microwave billiard with attached
      waveguide were studied in dependence on the coupling strength [E. Persson et al.,
      Phys. Rev. Lett. 85, 2478 (2000)], and resonance trapping was experimentally
      found. In the present paper an effective Hamiltonian is derived that depends
      exclusively on billiard and waveguide geometry. Its eigenvalues give the poles of
      the scattering matrix provided that the system and environment are defined
      adequately. Further, we present the results of resonance trapping measurements
      where, in addition to our previous work, the position of the slit aperture within
      the waveguide was varied. Numerical simulations with the derived Hamiltonian
      qualitatively reproduce the experimental data.

PMID- 12188820
TI  - Synchronization of chaos in microchip lasers by using incoherent feedback.
AB  - We propose a chaos-synchronization scheme using incoherent feedback to the
      pumping power in two microchip lasers. The population inversion of the slave
      laser is controlled for synchronization by using the detected signals of the peak
      heights of chaotic pulse intensities in the two lasers. Matching of the optical
      frequencies between the two lasers (i.e., injection locking) is not required for
      synchronization using this method. We numerically demonstrate the incoherent
      feedback method and investigate synchronization regions against parameter
      mismatching between the two lasers. Synchronization is maintained within a
      mismatching of 1% for all laser parameters, which implies that the difficulty in
      reproducing the synchronized laser pulses is very useful for applications of
      secure optical communications.

PMID- 12188821
TI  - Transition among synchronized states mediated by attractor-repeller collision
      crisis.
AB  - We studied the transition from a single-value generalized synchronization state
      to a double-value one in a unidirectionally coupled two-dimensional map system.
      It is found that this discontinuous transition is mediated by the attractor
      repeller collision crisis and is different from the blowout bifurcation in many
      respects. By using the unstable periodic orbits decomposition method, it is shown
      that the attractor is generally nondifferential in the parameter regime about the
      transition. Based on the nondifferential character of the attractor, we propose a
      mechanism for the attractor-repeller collision crisis.

PMID- 12188822
TI  - Transition at dissipative scales in large-Reynolds-number turbulence.
AB  - Among the available diagnostics of turbulence, the flatness of the velocity
      derivatives is particularly interesting because it represents a straightforward
      test of Kolmogorov theory, and provides a quantitative estimate for intermittency
      effects. It is commonly considered that the flatness factor increases with the
      Reynolds number, following a power law at high Reynolds numbers. At variance with
      this picture, evidence for a transitional behavior, taking place around the
      Taylor microscale Reynolds number R(lambda)=700, has been recently obtained in
      several experiments. In the present paper we study this transition in detail, and
      show it has the characteristics of a second order phase transition. We propose a
      physical picture for this transition, based on worm vortex breakdown, which leads
      as to suggest that intense sub-Kolmogorov structures might develop above the
      transition point. These results indicate that the existence of an asymptotic
      state at infinite Reynolds number may become questionable and more generally,
      that our current views on dissipative range intermittency probably need to be
      revised

PMID- 12188823
TI  - Second-order structure function scaling derivation from the Euler and
      magnetohydrodynamic equations.
AB  - An anomalous scaling paradigm that has recently come to be canonical has two
      features limiting its range of applicability: The driving and driven fields are
      separated dyamically and the driving field statistics is prescribed, in terms of
      the (inertial subrange) scaling of its second-order structure functions and of
      white-noise statistics in time. Then the spectrum of scaling exponents for the
      driven field, scalar or vector, depends parametrically on the driving. Here, the
      coupling of turbulent vorticity to the driving velocity field is considered.
      Using simple approximations and no white-noise statistics assumption, equations
      are derived for the evolution of two-point second-order correlations. The
      turbulent magnetohydrodynamic (MHD) case is treated in an analogous fashion. In
      the neutral case, the kinematic coupling between vorticity and velocity leads to
      a unique prediction for the scaling exponent of the second-order structure
      functions of the two turbulent fields. The velocity scaling exponent estimate is
      zeta(2)=3(1/2)-1 approximately equal to 0.732, i.e., close to experimental data.
      Unlike Kolmogorov scaling, this result is systematically derived from the Euler
      equations. The analogous scaling of MHD fields is now treated beyond the dynamo
      theory approximation. In contrast to the uniqueness found in the neutral case,
      predicted MHD scalings depend on one parameter, similar to the "plasma beta"
      parameter beta(T) relating kinetic to magnetic energy. The nature of predicted
      dependence of inertial-range scaling exponents on beta(T) agrees with an observed
      dichotomy between high-beta(T) and low-beta(T) turbulence regimes.

PMID- 12188824
TI  - Extended self-similarity and hierarchical structure in turbulence.
AB  - We show that a generalization of the She-Leveque hierarchical structure [Z.S. She
      and E. Leveque, Phys. Rev. Lett. 72, 336 (1994)] together with a constant maximum
      magnitude of the velocity difference give rise to the extended self-similarity
      (ESS) [R. Benzi et al., Phy. Rev. E 48, R29 (1993)]. Our analysis thus suggests
      that the ESS measured in turbulent flows is an indication of the most intense
      structures being shocklike. Analyses of velocity measurements in a turbulent pipe
      flow support our conjecture.

PMID- 12188825
TI  - Phase relaxation of Faraday surface waves.
AB  - Surface waves on a liquid-air interface excited by a vertical vibration of a
      fluid layer (Faraday waves) are employed to investigate the phase relaxation of
      ideally ordered patterns. By means of a combined frequency-amplitude modulation
      of the excitation signal a periodic expansion and dilatation of a square wave
      pattern is generated, the dynamics of which is well described by a Debye
      relaxator. By comparison with the results of a linear theory, it is shown that
      the measured relaxation time allows a precise evaluation of the phase diffusion
      constant.

PMID- 12188826
TI  - Dissipation of kinetic energy in two-dimensional bounded flows.
AB  - The role of no-slip boundaries as an enstrophy source in two-dimensional (2D)
      flows has been investigated for high Reynolds numbers. Numerical simulations of
      normal and oblique dipole-wall collisions are performed to investigate the
      dissipation of the kinetic energy E(t), and the evolution of the enstrophy
      Omega(t) and the palinstrophy P(t). It is shown for large Reynolds numbers that
      dE(t)/dt=-2Omega(t)/Re proportional, variant 1/sqrt[Re] instead of the familiar
      relation dE(t)/dt proportional, variant 1/Re as found for 2D unbounded flows.

PMID- 12188828
TI  - Tunable front interaction and localization of periodically forced waves.
AB  - In systems that exhibit a bistability between nonlinear traveling waves and the
      basic state, pairs of fronts connecting these two states can form localized wave
      pulses whose stability depends on the interaction between the fronts. We
      investigate wave pulses within the framework of coupled Ginzburg-Landau equations
      describing the traveling-wave amplitudes. We find that the introduction of
      resonant temporal forcing results in a tunable mechanism for stabilizing such
      wave pulses. In contrast to other localization mechanisms the temporal forcing
      can achieve localization by a repulsive as well as by an attractive interaction
      between the fronts. Systems for which the results are expected to be relevant
      include binary-mixture convection and electroconvection in nematic liquid
      crystals.

PMID- 12188827
TI  - Prandtl number dependence of the viscous boundary layer and the Reynolds numbers
      in Rayleigh-Benard convection.
AB  - We report results from high Prandtl number turbulent thermal convection
      experiments. The viscous boundary layer and the Reynolds number are measured in
      four different fluids over wide ranges of the Prandtl number Pr and the Rayleigh
      number Ra, all in a single convection cell of unity aspect ratio. We find that
      the normalized viscous layer thickness may be represented as
      delta(v)/L=0.65Pr(0.24)Ra(-0.16). The Reynolds number based on the oscillation
      frequency of the large-scale flow is found as Re(o)(Ra,Pr)=1.1Ra(0.43)Pr(-0.76)
      and that based on the rms velocity Re(rms)(Ra,Pr)=0.84Ra(0.40)Pr-0.86. Both the
      Ra and the Pr exponents of Re(V(m))(Ra,Pr) based on the maximum velocity of the
      circulating wind appear to vary across the range of Pr covered, changing from 0.5
      to 0.68 and -0.88 to -0.95, respectively, as Pr is increased from 6 to 1027.

PMID- 12188829
TI  - Theoretical investigation of the increase in the Rosseland mean opacity for hot
      dense mixtures.
AB  - Based on a detailed configuration accounting model with the term structures
      treated by the unresolved transition array model, a large scale calculation has
      been performed for the opacities of medium- and high-Z materials and mixtures.
      Agreement between our calculated results and previous theoretical simulations is
      obtained. By filling in the low-opacity regions of one material with the high
      opacity regions of other materials, the Rosseland mean opacity of their
      combination will be increased. This should be of great interest to hohlraum
      design in indirect-drive inertial confinement fusion. Based on our studies, many
      mixtures, such as Au+Nd, or Ho+Sn, can result in a similar (or higher) increase
      in the Rosseland mean as the previously proposed Au+Gd mixture.

PMID- 12188830
TI  - Dispersion relations of longitudinal and transverse waves in two-dimensional
      screened Coulomb crystals.
AB  - Dispersion relations of longitudinal and transverse waves in two-dimensional (2D)
      screened-Coulomb crystals were investigated. The waves were excited in 2D
      crystals made from complex plasmas, i.e., dusty plasmas, by applying radiation
      pressure of laser light. The dependencies of the dispersion relation on the
      shielding parameter, the damping rate, and the wave propagation direction were
      experimentally measured. The measured dispersion relations agree reasonably with
      a recently developed theory, and the comparison yields the shielding parameter
      and the charge on particles.

PMID- 12188831
TI  - Measurements of anomalous particle and energy fluxes in a magnetized plasma.
AB  - Electrostatic probe measurements of low frequency plasma fluctuations and
      anomalous particle and energy flux densities in a magnetized plasma are
      presented. A method allowing the simultaneous recording of instantaneous electric
      field, electron density, and temperature is invoked. The method is applied to
      flux density measurements in a weakly ionized, low beta plasma created in a
      toroidal device without magnetic rotational transform. It is also used to
      identify modes belonging to different dispersion branches and to obtain the
      dispersion relations for these modes. For the plasma states studied, the phase
      velocities and the cross phase between the electron density and electric field
      agree with those predicted from a local, linear stability analysis for
      electrostatic flute modes and drift waves. The instability threshold, however, is
      one order of magnitude higher than predicted by theory for unsheared flow. The
      fluxes measured are consistent with the estimated ionization rate.

PMID- 12188832
TI  - Interaction of soft-x-ray thermal radiation with foam-layered targets.
AB  - We have studied the interaction of soft-x-ray thermal radiation with foam-layered
      metal targets. X-ray radiation was produced by focusing a high-energy laser
      inside a small size hohlraum. An increment in shock pressure, up to a factor of
      approximately 4 for 50 mg/cm(3) foam density, was observed with the foam layer as
      compared to bare metal targets. This follows from the propagation of radiation
      driven shock wave in the foam and the impedance mismatch at the foam-payload
      interface.

PMID- 12188833
TI  - Stability of a mass accreting shell expanding in a plasma.
AB  - A linearized analysis is presented of the stability of a shell which accretes
      mass as it expands in a plasma under the push of the electromagnetic radiation
      trapped inside it. The interaction with the radiation is described in terms of a
      ponderomotive force and the shell dynamics is treated within the snowplow
      approximation. The mass accretion and the radiation expansion are shown to affect
      the stability of planar, cylindrical, and spherical shells differently.

PMID- 12188834
TI  - Interaction of a relativistic soliton with a nonuniform plasma.
AB  - By using a relativistic fluid model, a nonlinear theory for the propagation of an
      intense laser pulse in an inhomogeneous cold plasma is developed. Assuming that
      the radiation spot size is larger than the plasma wavelength, we derive an
      envelope equation for the momentum of the electron fluid, taking into account
      relativistic electron mass variation and finite amplitude electron density
      perturbations that are driven by the relativistic ponderomotive force of light.
      Localized solutions of the envelope equation are discussed from an energy
      integral containing an effective potential. Numerical results for envelope
      solitons are obtained in a quasistationary approximation. The dependency of these
      localized solutions on the amplitude and the group velocity of the laser pulse is
      discussed. Also derived is an equation that governs the dynamics of the pulse
      center.

PMID- 12188835
TI  - Analytic solution for low-frequency rf sheaths in pulsed discharges.
AB  - The equations governing the evolution of rf-driven sheaths are solved
      analytically in the regime where the rf frequency is small compared to both the
      ionic plasma frequency and the ion transit time in the sheaths. Poincare's map of
      first return is used to gain geometric insight into the dynamics of the circuit
      sheath system. The requirements of minimizing wall bombardment while maximizing
      the efficiency of the coupling to the substrate sheath are shown to lead to an
      optimum value for the blocking capacitance in asymmetric discharges. This optimum
      value is also favorable for rapid relaxation to the steady state in pulsed
      discharges. The analytic solution is applied to the problem of negative-ion
      extraction in afterglow plasmas.

PMID- 12188836
TI  - Nonlinear development of electron-beam-driven weak turbulence in an inhomogeneous
      plasma.
AB  - The self-consistent description of Langmuir wave and ion-sound wave turbulence in
      the presence of an electron beam is presented for inhomogeneous nonisothermal
      plasmas. Full numerical solutions of the complete set of kinetic equations for
      electrons, Langmuir waves, and ion-sound waves are obtained for an inhomogeneous
      unmagnetized plasma. The results show that the presence of inhomogeneity
      significantly changes the overall evolution of the system. The inhomogeneity is
      effective in shifting the wave numbers of the Langmuir waves, and can thus switch
      between different processes governing the weakly turbulent state. The results can
      be applied to a variety of plasma conditions, where we choose solar coronal
      parameters as an illustration, when performing the numerical analysis.

PMID- 12188837
TI  - Inhibition in the propagation of fast electrons in plastic foams by resistive
      electric fields.
AB  - The propagation of relativistic electrons in foam and solid density targets has
      been studied by means of K-alpha spectroscopy. Experimental results point out the
      role of self-generated electric fields in propagation and the role of heating of
      matter induced by the passage of fast electrons. A simple analytical formulation
      has been given and Spitzer conductivity has been shown to be fairly compatible
      with experimental results.

PMID- 12188838
TI  - Time evolution of Lyman-alpha fine-structure components for Al XIII.
AB  - We present a comparison of measured and theoretically modeled Lyman-alpha
      intensity ratios of hydrogenlike Al XIII impurity ions in a deuterium base plasma
      in the COMPASS-D tokamak. The time evolution of the intensity ratios is computed
      from a collisional-radiative model using measured plasma parameters and compared
      with line-of-sight integral values measured using a high-resolution crystal
      spectrometer. The variations in the modeled values follow the experimental data
      in the case of the L-mode plasma, taking into account variations in the electron
      parameters during the discharges. Apparent discrepancies between the observed and
      calculated ratios in the case of the H-mode plasma are attributed to line
      blending due to satellites of nearby Fe emission.

PMID- 12188839
TI  - Optimization of Kalpha bursts for photon energies between 1.7 and 7 keV produced
      by femtosecond-laser-produced plasmas of different scale length.
AB  - The conversion efficiency of a 90 fs high-power laser pulse focused onto a solid
      target into x-ray Kalpha line emission was measured. By using three different
      elements as target material (Si, Ti, and Co), interesting candidates for fast x
      ray diffraction applications were selected. The Kalpha output was measured with
      toroidally bent crystal monochromators combined with a GaAsP Schottky diode.
      Optimization was performed for different laser intensities as well as for
      different density scale lengths of a preformed plasma. These different scale
      lengths were realized by prepulses of different intensities and delay times with
      respect to the main pulse. Whereas the Kalpha yield varied by a factor of 1.8 for
      different laser intensities, the variation of the density scale length could
      provide a gain factor up to 4.6 for the Kalpha output.

PMID- 12188840
TI  - Structure of electromagnetic field excited by an electron bunch in a semi
      infinite dielectric-filled waveguide.
AB  - The exact solution of a problem on electromagnetic field excitation by a thin
      annular charged bunch in a semi-infinite round cylindrical waveguide with metal
      sidewalls and solid homogeneous dielectric filling is obtained. Expressions for
      all components of electromagnetic field are derived. These formulas describe the
      excited field at any point and any moment of time. In contrast to previous works,
      where asymptotic methods (saddle-point technique) were used, we applied a number
      of successive conformal transformations of integration area in order to carry out
      the inverse Fourier transformation. Integration along the initial infinite
      straight-line contour was substituted by integration along the closed circular
      contour. This allowed us to separate out the integral presentation of the
      cylindrical Bessel function of first kind and obtain the final solution in the
      form of infinite converging series. The process of integration is presented in
      detail. Both cases, when the Cherenkov resonance condition is satisfied and when
      this condition is not satisfied, are considered. Spatial pictures of field
      excited by a finite-size electron bunch are calculated numerically and discussed.
      In the case of the Cherenkov resonance the drift of excited wake field after the
      bunch with group velocity is demonstrated, and in the nonresonance case the
      appearance of impulse of transition radiation and the presence of precursor of
      the signal are shown.

PMID- 12188841
TI  - Ferrite-guided cyclotron-resonance maser.
AB  - The concept of a cyclotron-resonance maser (CRM) with a ferrite loading
      incorporated in its waveguide is proposed. The CRM interaction occurs between the
      rotating electron beam and the em wave propagating along a longitudinally
      magnetized ferrite medium. The ferrite anisotropic permeability resembles the CRM
      susceptibility in many aspects, and particularly in their similar response to the
      axial magnetic field (the ferrite susceptibility can be regarded as a passive
      analog of the active CRM interaction). The ferrite loading slows down the phase
      velocity of the em wave and thus the axial (Weibel) mechanism of the CRM
      interaction dominates. The ferrite loading enables also a mechanism of spectral
      tunability for CRM's. The ferrite loading is proposed, therefore, as a useful
      ingredient for high-power CRM devices. A linear model of the combined ferrite
      guided CRM interaction reveals its useful features. Future schemes may also
      incorporate ferrite sections functioning as isolators, gyrators, or phase
      shifters within the CRM device itself for selective suppression of backward waves
      and spurious oscillations, and for gain and efficiency enhancement.

PMID- 12188842
TI  - Amplified-spontaneous-emission power oscillation in a beam-wave interaction.
AB  - We present in this paper compelling evidence supporting the three-wave traveling
      wave theory developed by Pierce fifty years ago. The transition in a Smith
      Purcell free-electron laser from low, through moderate amplified spontaneous
      emission, to strong gain conditions was carefully controlled. Below threshold,
      the emitted far-infrared power exhibits oscillations with a cubic dependence on
      the electron beam current. Both characteristics are expected in a three-wave
      interaction yet, to date, have not been observed.

PMID- 12188843
TI  - Coherent synchrotron radiation transient effects in the energy-dependent region.
AB  - Coherent synchrotron radiation (CSR) is a well known phenomenon that originates
      from coherent superposition of electromagnetic waves by ultrarelativistic
      electrons. CSR longitudinal effects during the passage of a Gaussian beam from a
      straight to a circular path have often been studied in a regime in which they are
      energy independent. Nevertheless, the approximations used in such a regime may
      fail in several practical situations, as in the case of low-energy injectors or
      for small-wavelength structures within the bunch distribution in CSR-related
      instability problems. These situations demand a deeper investigation of
      longitudinal transient effects in the region where the approximations above are
      no longer valid: a strong gamma dependence is found, and described in this paper,
      in the rate of energy change induced by CSR during the transient of a Gaussian
      bunch between a straight and a circular path, which was studied with the help of
      the authors' previous work. Results show that the overall CSR longitudinal
      effects, in this case, are reduced. One of the outcomes of previous work by
      Saldin et al. was extended to this situation and very good agreement between the
      two studies was found.

PMID- 12188844
TI  - Quadrupole-mode transfer function and the nonlinear Mathieu instability.
AB  - We show that the quadrupole-mode transfer function (QTF) is a powerful
      nondestructive tool to measure properties of dynamical systems. In particular, we
      discuss the feasibility of using the QTF to measure the betatron tunes and the
      beam emittances with a beam-position monitor system. The QTF can also be used to
      compensate the optical mismatch during the beam injection process. However, it is
      less effective than the rf dipole method in overcoming the intrinsic spin
      resonances for polarized beam acceleration.

PMID- 12188845
TI  - Evolution of separate screening soliton pairs in a biased series photorefractive
      crystal circuit.
AB  - This paper presents calculations for an idea in photorefractive spatial soliton,
      namely, screening solitons form in a biased series photorefractive crystal
      circuit consisting of two photorefractive crystals connected electronically by
      electrode leads in a chain with a voltage source. A system of two coupled
      equations is derived under appropriate conditions for two-beam propagation in the
      crystal circuit. The possibility of obtaining steady-state bright and dark
      screening soliton solutions is investigated in one dimension and, the existence
      of dark-dark, bright-dark, and bright-bright separate screening soliton pairs in
      such a circuit is proved. The numerical results show that the two solitons in a
      soliton pair can affect each other by the light-induced current and their
      coupling can affect their spatial profiles, dynamical evolutions, stabilities,
      and self-deflection. Under the limit in which the optical wave has a spatial
      extent much less than the width of the crystal, only the dark soliton can affect
      the other soliton by the light-induced current, but the bright soliton cannot.
      For a bright-dark or dark-dark soliton pair, the dark soliton in a weak input
      intensity can be obtained for a larger nonlinearity than for a stronger input
      intensity. For a bright-dark soliton pair, increasing the input intensity of the
      dark soliton can increase the bending angle of the bright soliton. Some potential
      applications are discussed.

PMID- 12188846
TI  - Effect of dielectric responses on localization in one-dimensional random periodic
      on-average layered systems.
AB  - Dielectric response effects on wave localization in random periodic-on-average
      layered systems are studied. Based on Monte Carlo simulations and products of
      random matrices, statistics of the Lyapunov exponent are determined efficiently
      for very long systems. An oscillatory behavior for Lyapunov exponent is found and
      explained for mildly strong scattering conditions. We also show the emergence of
      strongly localized states in metallic layered systems with intermediate disorder
      for frequencies above the plasma frequency omega(p) of metals, as is not shown in
      dielectrics. Furthermore, the violation of universal single parameter scaling
      behaviors in different regimes of multiple scattering is discussed.

PMID- 12188847
TI  - Controlling the anisotropy of holographic polymer-dispersed liquid-crystal
      gratings.
AB  - In this work we investigate the optical properties of electrically switched
      transmission gratings fabricated holographically using polymer-dispersed liquid
      crystal (PDLC) materials. We have found that the PDLC mixture can be used to
      control the diffractive properties of the liquid-crystal composite gratings. In
      one limit the gratings are highly isotropic and in the other limit the gratings
      are highly anisotropic with a large birefringence. The experimental results are
      compared to theories that include the birefringence of the grating. From
      theoretical fits to the experimental data, measurements of the liquid-crystal
      distribution and alignment are obtained.

PMID- 12188848
TI  - Liquid light condensates.
AB  - We show that a laser beam which propagates through a cubic-quintic nonlinear
      optical material may reach, for a given power, a condensed state with a
      collisional dynamics resembling a liquid drop. We qualitatively describe the
      analogies between this system and the usual fluids and show them by simulating
      numerically total reflections of these beams with planar boundaries and localized
      defects. We use the analogy "liquid light" to stress the connections with the
      dynamics of quantum fluids, including Bose-Einstein condensates.

PMID- 12188849
TI  - Diffusing acoustic wave spectroscopy.
AB  - We have developed a technique in ultrasonic correlation spectroscopy called
      diffusing acoustic wave spectroscopy (DAWS). In this technique, the motion of the
      scatterers (e.g., particles or inclusions) is determined from the temporal
      fluctuations of multiply scattered sound. In DAWS, the propagation of multiply
      scattered sound is described using the diffusion approximation, which allows the
      autocorrelation function of the temporal field fluctuations to be related to the
      dynamics of the multiply scattering medium. The expressions relating the temporal
      field autocorrelation function to the motion of the scatterers are derived,
      focusing on the types of correlated motions that are most likely to be
      encountered in acoustic measurements. The power of this technique is illustrated
      with ultrasonic data on fluidized suspensions of particles, where DAWS provides a
      sensitive measure of the local relative velocity and strain rate of the suspended
      particles over a wide range of time and length scales. In addition, when combined
      with the measurements of the rms velocity of the particles using dynamic sound
      scattering, we show that DAWS can be used to determine the spatial extent of the
      correlations in the particle velocities, thus indirectly measuring the particle
      velocity correlation function. Potential applications of diffusing acoustic wave
      spectroscopy are quite far reaching, ranging from the ultrasonic nondestructive
      evaluation of the dynamics of inhomogeneous materials to geophysical studies of
      mesoscopic phenomena in seismology.

PMID- 12188850
TI  - Singular and regular gap solitons between three dispersion curves.
AB  - A general model is introduced to describe a wave-envelope system for the
      situation when the linear dispersion relation has three branches, which in the
      absence of any coupling terms between these branches, would intersect pairwise in
      three nearly coincident points. The system contains two waves with a strong
      linear coupling between them, to which a third wave is then coupled. This model
      has two gaps in its linear spectrum. As is typical for wave-envelope systems, the
      model also contains a set of cubic nonlinear terms. Realizations of this model
      can be made in terms of temporal or spatial evolution of optical fields in,
      respectively, either a planar waveguide, or a bulk-layered medium resembling a
      photonic-crystal fiber, which carry a triple spatial Bragg grating. Another
      physical system described by the same general model is a set of three internal
      wave modes in a density-stratified fluid, whose phase speeds come into close
      coincidence for a certain wave number. A nonlinear analysis is performed for zero
      velocity solitons, that is, they have zero velocity in the reference frame in
      which the third wave has zero group velocity. If one may disregard the self-phase
      modulation (SPM) term in the equation for the third wave, we find an analytical
      solution which shows that there simultaneously exist two different families of
      solitons: regular ones, which may be regarded as a smooth deformation of the
      usual gap solitons in a two-wave system, and cuspons, which have finite amplitude
      and energy, but a singularity in the first derivative at their center. Even in
      the limit when the linear coupling of the third wave to the first two nearly
      vanishes, the soliton family remains drastically different from that in the
      uncoupled system; in this limit, regular solitons whose amplitude exceeds a
      certain critical value are replaced by peakons (whose first derivative is finite
      at the center, but jumps in value). While the regular solitons, cuspons, and
      peakons are found in an exact analytical form, their stability is tested
      numerically, which shows that they all may be stable. If the SPM terms are
      retained, we find that there may again simultaneously exist two different
      families of generic stable soliton solutions, namely, regular ones and peakons.
      Direct simulations show that both types of solitons are stable in this case.

PMID- 12188851
TI  - Symmetries and invariant solutions of the planar paraxial wave equation in
      photosensitive media.
AB  - We study the equations describing planar self-written waveguides through group
      theoretical methods. We show the equations are nonintegrable through Painleve
      analysis. Using Lie group analysis we construct a class of exact solutions for
      this problem. We also show the previously reported modal ansatz solutions can be
      recovered from our present results as a special case.

PMID- 12188852
TI  - Direct perturbation theory for solitons of the derivative nonlinear Schrodinger
      equation and the modified nonlinear Schrodinger equation.
AB  - A direct perturbation theory for solitons of the derivative nonlinear Schrodinger
      (DNLS) equation is developed based on a closure of eigenfunctions of the
      linearized DNLS equation around a one-soliton solution. The slow evolution of
      soliton parameters and the perturbation-induced radiation are obtained. Under the
      known simple gaugelike transformation, these results are transformed into those
      for the perturbed modified nonlinear Schrodinger (MNLS) equation describing
      propagation of femtosecond pulses in optical fibers. A calculation of the
      perturbation-induced radiation fields for the perturbed DNLS and MNLS equations
      is also made. Our results for the perturbed MNLS equation can be reduced
      perfectly to those for the perturbed nonlinear Schrodinger equation in the small
      nonlinear-dispersion limit.

PMID- 12188853
TI  - Photon migration in turbid media using a cumulant approximation to radiative
      transfer.
AB  - A photon transport model for light migration in turbid media based on a cumulant
      approximation to radiative transfer is presented for image reconstruction inside
      an infinite medium or a bounded medium with a planar geometry. This model treats
      weak inhomogeneities through a Born approximation of the Boltzmann radiative
      transfer equation and uses the second-order cumulant solution of photon density
      to the Boltzmann equation as the Green's function for the uniform background. It
      provides the correct behavior of photon migration at early times and reduces at
      long times to the center-moved diffusion approximation. At early times, it agrees
      much better with the result from the Monte Carlo simulation than the diffusion
      approximation. Both approximations agree well with the Monte Carlo simulation at
      later times. The weight function for image reconstruction under this proposed
      model is shown to have a strong dependence at both early and later times on
      absorption and/or scattering inhomogeneities located in the propagation direction
      of and close to the source, or in the field of view of and close to the detector.
      This effect originates from the initial ballistic motion of incident photons,
      which is substantially underestimated by the diffusion approximation.

PMID- 12188855
TI  - Perturbation theory for Maxwell's equations with shifting material boundaries.
AB  - Perturbation theory permits the analytic study of small changes on known
      solutions, and is especially useful in electromagnetism for understanding weak
      interactions and imperfections. Standard perturbation-theory techniques, however,
      have difficulties when applied to Maxwell's equations for small shifts in
      dielectric interfaces (especially in high-index-contrast, three-dimensional
      systems) due to the discontinuous field boundary conditions--in fact, the usual
      methods fail even to predict the lowest-order behavior. By considering a sharp
      boundary as a limit of anisotropically smoothed systems, we are able to derive a
      correct first-order perturbation theory and mode-coupling constants, involving
      only surface integrals of the unperturbed fields over the perturbed interface. In
      addition, we discuss further considerations that arise for higher-order
      perturbative methods in electromagnetism.

PMID- 12188854
TI  - Isotropic versus anisotropic modeling of photorefractive solitons.
AB  - The question of the isotropic versus anisotropic modeling of incoherent spatial
      screening solitons in photorefractive crystals is addressed by a careful
      theoretical and numerical analysis. Isotropic, or local, models allow for an
      extended spiraling of two interacting scalar solitons, and for a prolonged
      propagation of vortex vector solitons, whereas anisotropic, nonlocal, models
      prevent such phenomena. In the context of Kukhtarev's material equations, the
      difference in behavior is traced to the continuity equation for the current
      density. We further show that neither an indefinite spiraling of two solitons nor
      stable propagation of vortex vector solitons is generally possible in both
      isotropic and anisotropic models. Such systems do not conserve angular momentum,
      even in the case of an isotropic change in the index of refraction.

PMID- 12188856
TI  - Designing localized electromagnetic fields in a source-free space.
AB  - An approach to characterizing and designing localized electromagnetic fields,
      based on the use of differentiable manifolds, differentiable mappings, and the
      group of rotation, is presented. By way of illustration, novel families of exact
      time-harmonic solutions to Maxwell's equations in the source-free space-
      localized fields defined by the rotation group--are obtained. The proposed
      approach provides a broad spectrum of tools to design localized fields, i.e., to
      build-in symmetry properties of oscillating electric and magnetic fields, to
      govern the distributions of their energy densities (both size and form of
      localization domains), and to set the structure of time-average energy fluxes. It
      is shown that localized fields can be combined as constructive elements to obtain
      a complex field structure with desirable properties, such as one-, two-, or three
      dimensional field gratings. The proposed approach can be used in designing
      localized electromagnetic fields to govern motion and state of charged and
      neutral particles. As an example, motion of relativistic electrons in one
      dimensional and three-dimensional field gratings is treated.

PMID- 12188857
TI  - Partial-differential-equation-based approach to classical phase-space
      deformations.
AB  - This paper presents a partial-differential-equation-based approach to finding an
      optimal canonical basis with which to represent a nearly integrable Hamiltonian.
      The idea behind the method is to continuously deform the initial canonical basis
      in such a way that the dependence of the Hamiltonian on the canonical position of
      the final basis is minimized. The final basis incorporates as much of the
      classical dynamics as possible into an integrable Hamiltonian, leaving a much
      smaller nonintegrable component than in the initial representation. With this
      approach it is also possible to construct the semiclassical wave functions
      corresponding to the final canonical basis. This optimized basis is potentially
      useful in quantum calculations, both as a way to minimize the required size of
      basis sets, and as a way to provide physical insight by isolating those effects
      resulting from integrable dynamics.

PMID- 12188858
TI  - Bright compact breathers.
AB  - In this communication we will consider the potential of some general classes of
      nonlinear lattice models to support bright discrete compact breather solutions
      (compactlets). We analyze the conditions for which such solutions are possible
      and classify the models as belonging in three general categories: a class with no
      compact breather solutions, one with one-parameter families of solutions, and a
      class with "isolated" solutions (i.e., no free parameters). In the latter two
      cases we construct the solutions and analyze their linear stability. The
      drastically different stability features of these solutions in comparison with
      their smoothly decaying counterparts are discussed. Stable breather solutions
      with compact support are identified in the one-parameter families of solutions,
      while the corresponding solutions found in the zero-parameter families are always
      found to be unstable.

PMID- 12188859
TI  - Accelerating solitons for sliding-frequency filter systems.
AB  - The sliding-frequency filter equation is shown to have similarity solutions which
      travel with steady profile but with constant acceleration. Over a wide range of
      the gain, filter strength and sliding-rate parameters, the pulse envelope is very
      well approximated by a sech profile. However, when the sliding rate is large, the
      chirp differs greatly from the usually assumed linear variation of frequency
      through the pulse. The amplitude and chirp are found for small and moderate
      sliding rate by a perturbation analysis and, for larger sliding rates, by solving
      a nonlinear eigenvalue problem for a nonautonomous differential equation.

PMID- 12188860
TI  - Different approach for evaluating dissipation in macroscopic quantum tunneling.
AB  - The problem of evaluating dissipative effects in macroscopic quantum tunneling is
      re-examined for the case of Josephson junctions, with the adoption of an
      alternative way with respect to several previously proposed and, in some cases,
      contradictory approaches. The system, which consists of a junction coupled to a
      transmission line, is analyzed both analytically and numerically. A test of the
      theoretical model, as compared to the experimental results available, is
      performed in accordance with a criterion based on a shortening of the traversal
      time.

PMID- 12188861
TI  - Reference-wave solutions for the high-frequency field in random media.
AB  - Ray trajectories, as has been shown in the recently formulated stochastic
      geometrical theory of diffraction, play an important role in determining the
      propagation properties of high-frequency wave fields and their statistical
      measures in complicated random environments. The field at the observer can be
      presented as the superposition of a variety of field species arriving at the
      observer along multiple ray trajectories resulting from boundaries and scattering
      centers embedded into the random medium. In such situations the intensity
      products from which the average intensity measures can be constructed and which,
      in general, are presented as even products of the total field, will contain sums
      of products of mixed field species arriving along different ray trajectories. For
      computations of the statistical measures of the field it is desirable, therefore,
      to possess a solution for the high-frequency field propagating along an isolated
      ray trajectory. The main concern of this work is the construction of high
      frequency asymptotic propagators, relating the values of the random field and its
      statistical measures at some observation plane to their source (actual or
      virtual) distributions at the initial plane. For this reason a reference-wave
      method was developed to obtain an approximate solution of the parabolic wave
      equation in a homogeneous background random medium.

PMID- 12188862
TI  - Steady-state properties of single-file systems with conversion.
AB  - We have used Monte Carlo methods and analytical techniques to investigate the
      influence of the characteristic parameters, such as pipe length, diffusion,
      adsorption, desorption, and reaction rate constants on the steady-state
      properties of single-file systems with a reaction. We looked at cases when all
      the sites are reactive and when only some of them are reactive. Comparisons
      between mean-field predictions and Monte Carlo simulations for the occupancy
      profiles and reactivity are made. Substantial differences between mean-field and
      the simulations are found when rates of diffusion are high. Mean-field results
      only include single-file behavior by changing the diffusion rate constant, but it
      effectively allows passing of particles. Reactivity converges to a limit value if
      more reactive sites are added: sites in the middle of the system have little or
      no effect on the kinetics. Occupancy profiles show approximately exponential
      behavior from the ends to the middle of the system.

PMID- 12188863
TI  - Cluster hybrid Monte Carlo simulation algorithms.
AB  - We show that addition of Metropolis single spin flips to the Wolff cluster
      flipping Monte Carlo procedure leads to a dramatic increase in performance for
      the spin-1/2 Ising model. We also show that adding Wolff cluster flipping to the
      Metropolis or heat bath algorithms in systems where just cluster flipping is not
      immediately obvious (such as the spin-3/2 Ising model) can substantially reduce
      the statistical errors of the simulations. A further advantage of these methods
      is that systematic errors introduced by the use of imperfect random-number
      generation may be largely healed by hybridizing single spin flips with cluster
      flipping.

PMID- 12188864
TI  - Artificial neural networks for automation of Rutherford backscattering
      spectroscopy experiments and data analysis.
AB  - We present an algorithm based on artificial neural networks able to determine
      optimized experimental conditions for Rutherford backscattering measurements of
      Ge-implanted Si. The algorithm can be implemented for any other element implanted
      into a lighter substrate. It is foreseeable that the method developed in this
      work can be applied to still many other systems. The algorithm presented is a
      push-button black box, and does not require any human intervention. It is thus
      suited for automated control of an experimental setup, given an interface to the
      relevant hardware. Once the experimental conditions are optimized, the algorithm
      analyzes the final data obtained, and determines the desired parameters. The
      method is thus also suited for automated analysis of the data. The algorithm
      presented can be easily extended to other ion beam analysis techniques. Finally,
      it is suggested how the artificial neural networks required for automated control
      and analysis of experiments could be automatically generated. This would be
      suited for automated generation of the required computer code. Thus could RBS be
      done without experimentalists, data analysts, or programmers, with only
      technicians to keep the machines running.

PMID- 12188865
TI  - Path-integral study of a two-dimensional Lennard-Jones glass.
AB  - The glass transition in a quantum Lennard-Jones mixture is investigated by
      constant-volume path-integral simulations. Particles are assumed to be
      distinguishable, and the strength of quantum effects is varied by changing
      variant Planck's over 2pi from zero (the classical case) to one (corresponding to
      a highly quantum-mechanical regime). Quantum delocalization and zero point energy
      drastically reduce the sensitivity of structural and thermodynamic properties to
      the glass transition. Nevertheless, the glass transition temperature T(g) can be
      determined by analyzing the phase space mobility of path-integral centroids. At
      constant volume, the T(g) of the simulated model increases monotonically with
      increasing variant Planck's over 2pi. Low temperature tunneling centers are
      identified, and the quantum versus thermal character of each center is analyzed.
      The relation between these centers and soft quasilocalized harmonic vibrations is
      investigated. Periodic minimizations of the potential energy with respect to the
      positions of the particles are performed to determine the inherent structure of
      classical and quantum glassy samples. The geometries corresponding to these
      energy minima are found to be qualitatively similar in all cases. Systematic
      comparisons for ordered and disordered structures, harmonic and anharmonic
      dynamics, classical and quantum systems show that disorder, anharmonicity, and
      quantum effects are closely interlinked.

PMID- 12188866
TI  - Higher-order unconditionally stable algorithms to solve the time-dependent
      Maxwell equations.
AB  - For the recently introduced algorithms to solve the time-dependent Maxwell
      equations [J. S. Kole, M. T. Figge, and H. De Raedt, Phys. Rev. E 64, 066705
      (2001)], we construct a variable grid implementation and an improved spatial
      discretization implementation that preserve the exceptional property of the
      algorithms to be unconditionally stable by construction. We find that the
      performance and accuracy of the corresponding algorithms are significant and
      illustrate their practical relevance by simulating various physical model
      systems.

PMID- 12188867
TI  - Gap structure of the local field in symmetric Q Ising neural networks.
AB  - The time evolution of the local field in symmetric Q-Ising neural networks is
      studied for arbitrary Q. In particular, the structure of the noise and the
      appearance of gaps in the probability distribution are discussed. Results are
      presented for several values of Q and compared with numerical simulations.

PMID- 12188868
TI  - Fracture statistics of brittle materials: Weibull or normal distribution.
AB  - The fit of fracture strength data of brittle materials (Si(3)N(4), SiC, and ZnO)
      to the Weibull and normal distributions is compared in terms of the Akaike
      information criterion. For Si(3)N(4), the Weibull distribution fits the data
      better than the normal distribution, but for ZnO the result is just the opposite.
      In the case of SiC, the difference is not large enough to make a clear
      distinction between the two distributions. There is not sufficient evidence to
      show that the Weibull distribution is always preferred to other distributions,
      and the uncritical use of the Weibull distribution for strength data is
      questioned.

PMID- 12188869
TI  - Shnirelman peak in level spacing statistics of Calogero-like three-body problem.
AB  - Statistical properties of quantum quasidegeneracy in a Calogero-like three-body
      problem is presented. The hidden continuous symmetry of a Calogero problem is
      broken by adding a three-body interaction, which results in discrete symmetry.
      This symmetry is sufficient to get the Shnirelman peak in level spacing
      statistics. Our calculation immediately implicates the application of Shnirelman
      theorem in real physical quantum systems.

PMID- 12188870
TI  - Hierarchic trees with branching number close to one: Noiseless Kardar-Parisi
      Zhang equation with additional linear term for imitating two-dimensional and
      three-dimensional phase transitions.
AB  - An imitation of two-dimensional (2D) field theory is formulated by means of a
      model on the hierarchic tree (with branching number close to one) with the same
      potential and the free correlators identical to 2D correlator ones. Such a model
      carries on some features of the original model for certain scale invariant
      theories. The renormalization group equation for the free energy is the noiseless
      Kardar-Parisi-Zhang equation with an additional linear term.

PMID- 12188871
TI  - Chaotic diffusion of particles with finite mass in oscillating convection flows.
AB  - Deterministic diffusion in temporally oscillating convection is studied for
      particles with finite mass. The particles are assumed to obey a simple
      dissipative dynamical system and the particle diffusion is induced by the strange
      attractor. The diffusion constants are numerically calculated for convection
      models with free and rigid boundary conditions.

PMID- 12188872
TI  - Slower speed and stronger coupling: adaptive mechanisms of chaos synchronization.
AB  - We show that two initially weakly coupled chaotic systems can achieve
      synchronization by adaptively reducing their speed and/or enhancing the coupling
      strength. Explicit adaptive algorithms for speed reduction and coupling
      enhancement are provided. We apply these algorithms to the synchronization of two
      coupled Lorenz systems. It is found that after a long-time adaptive process, the
      two coupled chaotic systems can achieve synchronization with almost the minimum
      required coupling-speed ratio.

PMID- 12188873
TI  - Resonances via deterministic and stochastic perturbations: a comparative study.
AB  - We study periodic and coherence resonances invoked by aperiodic yet deterministic
      perturbations. Chaotic perturbations with varying levels of intrinsic
      correlations are superimposed parametrically on an excitable chemical model. This
      enables us to analyze the system response and characterize the induced resonances
      as a function of correlation in the perturbing signal. Using standard measures
      such as normalized variance and normalized number of peaks, dynamics for
      different deterministic signals are quantified and eventually compared to
      resonances invoked via stochastic perturbations.

PMID- 12188874
TI  - Localized perturbations of integrable quantum billiards.
AB  - The statistics of energy levels of a rectangular billiard that is perturbed by a
      strong localized potential are studied analytically and numerically, when this
      perturbation is at the center or at a typical position. Different results are
      found for these two types of position. If the scatterer is at the center, the
      symmetry leads to additional contributions, some of which are related to the
      angular dependence of the potential. The limit of the delta-like scatterer is
      obtained explicitly. The form factor, which is the Fourier transform of the
      energy-energy correlation function, is calculated analytically, in the framework
      of the semiclassical geometrical theory of diffraction, and numerically.
      Contributions of classical orbits that are nondiagonal are calculated and are
      found to be essential.

PMID- 12188875
TI  - Rhines scale and spectra of the beta-plane turbulence with bottom drag.
AB  - We study two-dimensional incompressible turbulence on the beta plane and propose
      a modification to the Rhines scale that takes into account the bottom friction.
      The modified Rhines scale is studied numerically, and found to predict accurately
      the jet number and the energy peak of the beta-plane turbulence for strong beta.
      The intermediate cases show a transition from the (isotropic) friction scale to
      the Rhines one, as the proper halting scale for the inverse cascade.

PMID- 12188876
TI  - Laser-plasma electron-density measurement using x-ray interferometry.
AB  - In this paper, the propagation of x-rays in laser-produced plasma is studied both
      analytically and numerically. The coupling relation between phase and amplitude
      of x-rays is derived, the solutions with higher-order corrections are given where
      the higher-order electron-density gradients have been taken into account. An
      important parameter eta was introduced, which is related to the errors of the
      electron-density measurement using x-ray interferometry. It is justified that so
      long as eta<1, the x-ray interferometry can be used for the measurement of
      electron density and for greater value of eta, higher-order modifications are
      needed.

PMID- 12188877
TI  - Exact discrete breather compactons in nonlinear Klein-Gordon lattices.
AB  - We demonstrate the existence of exact discrete compact breather solutions in
      nonlinear Klein-Gordon systems, and complete the work of Tchofo Dinda and
      Remoissenet [Phys. Rev. E 60, 6218 (1999)], by showing that the breathers
      stability is related principally to the lattice boundary conditions, the coupling
      term, and the harmonicity parameter.

PMID- 12188878
TI  - Antisense anticancer oligonucleotide therapeutics.
AB  - Recent progress made in molecular biology, biotechnology, and genetics,
      especially in identifying, cloning, sequencing and characterization of normal and
      pathogenic genes, has led to the development of genetic therapy. Major efforts in
      the field can be summarized in two general approaches: gene therapy and antisense
      therapy. The second is to deliver to the target cells antisense molecules that
      target to mRNA with which they can hybridize and specifically inhibit the
      expression of pathogenic genes. Antisense oligonucleotides offer the possibility
      of specific, rational, genetic-based therapeutics. With encouraging results from
      preclinical and clinical studies of antisense oligonucleotides in the past
      decade, significant progress has been made in developing antisense therapy, with
      the first antisense drug now being approved for clinical use. In this article, we
      will discuss approaches to developing these drugs from preclinical to clinical
      settings. Of particular interest for the area of human cancer therapy, several
      cancer targets, including bcl-2, BCR-ABL, C-raf-1, Ha-ras, c-myc, PKC, PKA, p53
      and MDM2, are reviewed as examples to illustrate the progress in this field and
      emphasize the importance of target selection and advanced antisense chemistry in
      the development of antisense therapy.

PMID- 12188879
TI  - Antisense and/or immunostimulatory oligonucleotide therapeutics.
AB  - Antisense technology, which is based on a simple and rational principle of Watson
      Crick complementary base pairing of a short oligonucleotide with the targeted
      mRNA to downregulate the disease-causing gene product, has progressed
      tremendously in the last two decades. Antisense oligonucleotides targeted to a
      number of cancer-causing genes are being evaluated in human clinical trials.
      While the first-generation phosphorothioate antisense oligonucleotides are in
      clinical trials, a number of factors, including sequence motifs that could lead
      to unwanted mechanisms of action and side effects, have been identified. The
      severity of the side effects of first-generation antisense oligonucleotides is
      mostly dependent on the presence of certain sequence motifs, such as CpG
      dinucleotides. A number of second-generation chemical modifications have been
      proposed to overcome the limitations of the first-generation antisense
      oligonucleotides. The safety and efficacy of several second-generation mixed
      backbone antisense oligonucleotides are being evaluated in clinical trials. The
      immune stimulation affects observed with CpG-containing antisense
      oligonucleotides are being exploited as a novel therapeutic modality, with
      several CpG oligonucleotides being evaluated in clinical trials. A number of
      medicinal chemistry studies performed to date suggest that the immunomodulatory
      activity of CpG oligonucleotides can be fine-tuned by site-specific incorporation
      of chemical modifications in order to design disease-specific oligonucleotide
      therapeutics.

PMID- 12188880
TI  - Modification of alternative splicing by antisense oligonucleotides as a potential
      chemotherapy for cancer and other diseases.
AB  - It has been estimated that greater than 35% of all human genes undergo
      alternative splicing. The process of alternative splicing is highly regulated and
      disruption of a splicing pattern can produce splice variants that have different
      functions. Certain splice variants that are associated with induction of cell
      death, regulation of cellular proliferation and differentiation, cell signaling,
      and angiogenesis are present in a variety of cancers. Several of these cancer
      related alternatively spliced genes will be discussed in this review. In
      addition, alternative splicing is associated with several genetic disorders such
      as beta-thalassemia, cystic fibrosis, and muscular dystrophy. Control of pre-mRNA
      splicing patterns with antisense oligonucleotides presents an attractive way to
      potentially treat and manage a variety of diseases. This review will discuss
      potential gene targets for antisense oligonucleotide induced modification of
      alternative splicing patterns. Furthermore, the chemistries and delivery
      strategies of antisense oligonucleotides will be discussed.

PMID- 12188881
TI  - Targeting of cancer-related proteins with PNA oligomers.
AB  - Aberrant gene expression is characteristic to all cancer cells and
      pathophysiology in general. Selective inhibition of constitutively elevated
      expression of oncogenes provides an opportunity to hinder the proliferation of
      malignant cells. Small synthetic molecules that specifically interfere with
      transcription and/or translation have great potential as anticancer drugs.
      Currently first-generation antisense oligonucleotides are widely used to inhibit
      the oncogene expression. The second generation of antisense agents have been
      studied mainly in vitro. One of these agents, peptide nucleic acid (PNA) is an
      oligonucleotide mimic with a non-charged achiral polyamide backbone to which the
      nucleobases are linked. PNA oligomers bind tightly to complementary DNA or RNA
      and are very stable in biological fluids. PNA can inhibit transcription and
      translation of target genes by specifically hybridizing to DNA or mRNA. The in
      vitro experiments showing inhibition of target protein expression by PNA have
      been followed by the first successful applications of PNA as an antisense agent
      in cultured cells and also in vivo. Hopefully this will lead to a wider use of
      PNA in the studies of cancer biology and therapy.

PMID- 12188882
TI  - D-RNAi (messenger RNA-antisense DNA interference) as a novel defense system
      against cancer and viral infections.
AB  - D-RNAi (Messenger RNA-antisense DNA interference), a novel posttranscriptional
      phenomenon of silencing gene expression by transfection of mRNA-aDNA hybrids, was
      originally observed in the effects of bcl-2 on phorbol ester-induced apoptosis in
      human prostate cancer LNCaP cells. This phenomenon was also demonstrated in
      chicken embryos and a human CD4(+) T cell line, H9. The in vivo transduction of
      beta-catenin D-RNAi was shown to knock out more than 99% endogenous beta-catenin
      gene expression, while the in cell transfection of HIV-1 D-RNAi homolog rejected
      viral gene replication completely. D-RNAi was found to have long-term gene
      knockout effects resulting from a posttranscriptional gene silencing mechanism
      that may involve the homologous recombination between intracellular mRNA and the
      mRNA components of a D-RNAi construct. These findings provide a potential
      intracellular defense system against cancer and viral infections.

PMID- 12188883
TI  - Selectively replicating adenoviruses for oncolytic therapy.
AB  - The most prevalent problem in cancer therapy is the regrowth and metastasis of
      malignant cells after standard treatment with surgery, radiation, and/or
      chemotherapy. Gene therapy approaches have suffered from the inadequate
      transduction efficiencies of replication-defective vectors that have been used
      thus far. Replication-competent vectors, particularly adenoviruses that cause
      cytolysis as part of their natural life cycle, represent an emerging technology
      that shows considerable promise as a novel treatment option, particularly for
      locally advanced or recurrent cancer. A number of oncolytic adenoviruses that are
      designed to replicate selectively in tumor cells by targeting molecular lesions
      inherent in cancer, or by incorporation of tissue-specific promoters driving the
      early genes that initiate viral replication, are currently being tested in
      clinical trials. The results of these clinical trials indicate that, in its
      current form, oncolytic adenovirus therapy shows the best results and achieves an
      enhanced tumoricidal effect when used in combination with chemotherapeutic agents
      such as cisplatin, leucovorin and 5-fluorouracil. Nevertheless, each of the
      oncolytic adenoviruses in current use exhibits characteristic shortcomings, and
      there is still considerable room for improvement. Current strategies for
      improving the selectivity and efficacy of oncolytic adenoviruses include
      molecular engineering of tumor cell-specific binding tropism, selective
      modifications of viral early genes and incorporation of cellular promoters to
      achieve tumor-specific replication, augmentation of anti-tumor activity by
      incorporation of suicide genes, and manipulation of the immune response.

PMID- 12188884
TI  - Selective destruction of tumor cells through specific inhibition of products
      resulting from chromosomal translocations.
AB  - A key problem in the effective treatment of patients with cancer (both leukemia
      and solid tumors) is to distinguish between tumor and normal cells. This problem
      is the main reason why current treatments for cancer are often ineffective. There
      have been remarkable advances in our understanding of the molecular biology of
      cancer that provides new selective tumor destruction mechanisms. The molecular
      characterization of the tumor-specific chromosomal abnormalities has revealed
      that fusion proteins are the consequence in the majority of cancers. These fusion
      proteins result from chimeric genes created by the translocations, which form
      chimeric mRNA species that contain exons from the genes involved in the
      translocation. Obviously, these chimeric molecules are attractive therapeutic
      targets since they are unique to the disease (they only exist in the tumor cells
      but not in the normal cells of the patient), allowing the design of specific anti
      tumor drugs. Inhibition of chimeric gene expression by anti-tumor agents
      specifically kills leukemic cells without affecting normal cells. As therapeutic
      agents targeting chimeric genes, zinc-finger proteins, antisense RNAs  or
      hammerhead-based ribozymes  have been used. All of these agents have some
      limitations, indicating that new therapeutic tools are required as gene
      inactivating agents that should be able to inhibit any chimeric fusion gene
      product. Recently, we have used the catalytic RNA subunit of RNase P from
      Escherichia coli, which can be specifically directed to cut any mRNA sequence, to
      specifically destroy tumor-specific fusion genes created as a result of
      chromosomal translocations. In this chapter, we will review the advances made to
      selectively destroy tumor cells through specific inhibition of products resulting
      from chromosomal translocations.

PMID- 12188885
TI  - Mutant cell surface receptors as targets for individualized cancer diagnosis and
      therapy.
AB  - The catalogue of gene alterations in human cancer is growing rapidly. Alterations
      in specific genes that play important roles in diverse cellular functions such as
      cell adhesion, signal transduction, differentiation, development or DNA-repair
      have been identified. Cancer-associated mutant cell surface molecules are very
      attractive candidates to target tumor cells because they offer the possibility of
      minimizing toxic effects to non-tumor cells. The cell adhesion molecule E
      cadherin has been shown to play a major role in determining which of the two
      subtypes of gastric cancer, diffuse or intestinal type, develops. E-cadherin gene
      mutations typically affect the extracellular portion of the homophilic receptor
      and are frequently found in patients with diffuse-type tumors. Cancer-specific
      monoclonal antibodies against the E-cadherin mutational hot spot region are now
      available. In cell culture and in animal studies we have shown that mutation
      specific antibodies exclusively target cells expressing abnormal E-cadherin.
      Those cells expressing the normal protein were not affected, demonstrating the
      specificity of our approach. After linking to toxins, drugs or radiolabeled
      mutation-specific antibodies could serve as very specific agents to treat small
      tumor deposits. Patients for this novel individualized cancer therapy can be
      identified within a day using routine immunohistochemistry of biopsies.

PMID- 12188886
TI  - Rational design of potent and selective EGFR tyrosine kinase inhibitors as
      anticancer agents.
AB  - Increasing knowledge of the structure and function of the Epidermal Growth Factor
      Receptor (EGFR) subfamily of tyrosine kinases, and of their role in the
      initiation and progression of various cancers has led to the search for
      inhibitors of signaling molecules that may prove to be important in cancer
      therapy. The complex nature of EGFR biology allows for potential opportunities
      for EGFR inhibitors in a number of areas of cancer therapy, including
      proliferative, angiogenic, invasive, and metastatic aspects. Different approaches
      have been used to target either the extracellular ligand-binding domain of the
      EGFR or the intracellular tyrosine kinase region that results in interference
      with its signaling pathways that modulate cancer-promoting responses. Examples of
      these include a number of monoclonal antibodies, immunotoxins and ligand-binding
      cytotoxic agents that target the extracellular ligand binding region of EGFR, and
      small molecule inhibitors that target the intracellular kinase domain and act by
      interfering with ATP binding to the receptor. During the past 3 years,
      significant progress has been made towards the identification of new structural
      classes of small molecule inhibitors that show high potency and specificity
      towards EGFR. The search for new small molecules that inhibit kinases has
      included traditional approaches like the testing of natural products, random
      screening of chemical libraries, the use of classical structure-activity
      relationship studies, and the incorporation of structure-based drug design and
      combinatorial chemistry techniques. There has been a significant improvement in
      the development of selective EGFR inhibitors with the use of a structure-based
      design approach employing a homology model of the EGFR kinase domain. Molecular
      modeling procedures have been used to generate novel molecules that are
      complementary in shape and electrostatics to the EGFR kinase domain topography.
      This review focuses on some examples of the successful use of this method.

PMID- 12188888
TI  - Microarrays: spotlight on gene function and pharmacogenomics.
AB  - The introduction of microarray technology has dramatically changed the way that
      researchers address many biomedical questions. DNA microarrays can measure
      expression of thousands of genes simultaneously, providing extensive information
      on gene interaction and function. Microarray technology is a powerful tool for
      identifying novel molecular drug targets and for elucidating mechanisms of drug
      action. Furthermore, microarrays can monitor the global profile of gene
      expression in response to specific pharmacologic agents, providing information on
      drug efficacy and toxicity. Over the last several years, dramatic advancements
      have occurred in array technology. In this review we describe basic aspects of
      microarray instrumentation and experimentation. Each of the major array formats
      including oligonucleotides arrays, spotted arrays, and macroarrays are examined,
      and advantages and options for using each format are presented. Important factors
      in the design and analysis of microarray experiments are also discussed. Most
      importantly, we explore recent developments in microarray technology that are
      relevant to pharmacogenomics and the discovery of gene function.

PMID- 12188887
TI  - Thymidine phosphorylase: a two-face Janus in anticancer chemotherapy.
AB  - Several cytokines and growth factors modulate angiogenesis through a fine tuned
      paracrine or autocrine mode of action. Among them is plateled-derived endothelial
      cell growth factor (PD-ECGF), which is highly is expressed in tumors, and is
      angiogenic by stimulation of endothelial cell migration. Studies have shown that
      PD-ECGF is identical to the well known enzyme thymidine phosphorylase (TP), which
      is involved in thymidine metabolism and homeostasis. Interestingly, PD-ECGF plays
      an angiogenic role as a result of its TP enzyme activity. In light of these
      findings, PD-ECGF/TP should not be considered a true growth factor, and its PD
      ECGF name is now actually a misnomer. Recently, TP activity was thought of as an
      interesting potential two-face target for controling tumor-dependent
      angiogenesis. In fact, on one hand, its high levels of expression in tumors
      compared to non-neoplastic regions, and its broad substrate specificity suggested
      that TP could be used as an enzymatic tool to locally activate anticancer
      nucleoside bases or base analogs. On the other hand, its enzyme-dependent
      angiogenic activity engendered the search for specific inhibitors to reduce TP
      dependent angiogenesis. This review will describe TP, its activity, its possible
      mechanisms of action and its role in angiogenesis. Particular attention will be
      focused on the design and biological characterization of novel TP inhibitors
      which recently showed promising anticancer activity.

PMID- 12188890
TI  - New drug targets for genomic cancer therapy: successes, limitations,
      opportunities and future challenges.
AB  - Cancer drug therapy is undergoing a major transition from the previous pregenomic
      cytotoxic era to the new postgenomic era. Future mechanism-based therapeutic
      agents will increasingly be designed to act on molecular targets that are
      causally involved in the malignant progression of human cancers. Such agents are
      predicted to show greater therapeutic selectivity for cancer versus normal cells.
      New cancer drug targets are identified and validated in various ways. The
      determination of the normal human genome sequence, followed by that of multiple
      cancer genomes, is accelerating target discovery. Other new technologies,
      particularly high throughput screening, combinatorial chemistry and gene
      expression microarrays, are increasing the speed and efficiency of drug
      development. Examples of new molecular therapeutics showing promising activity in
      the clinic include Herceptin, Glivec and Iressa. However, many challenges remain
      as we test the vision of individualised combinatorial genome-based therapy, using
      drugs targeted to every significant molecular abnormality in cancer.

PMID- 12188889
TI  - Challenges of cancer drug design: a drug metabolism perspective.
AB  - The time course and duration of action of drugs used in cancer chemotherapy are
      greatly influenced by the molecular and biochemical properties of enzymes
      associated with their metabolism. Variation in the response of individual
      patients to cancer chemotherapeutic agents is in large measure due to genetic and
      environmental factors that impinge on specific enzymes belonging to the two major
      classes of drug metabolizing enzymes. Current knowledge of the molecular biology
      and biochemistry of phase I drug metabolizing enzymes (cytochrome P450, flavin
      containing and xanthine oxidases, NADPH quinone reductase, and aldehyde and
      dihydropyridine dehydrogenases), and phase II enzymes (glucuronosyl-, sulfo-, N
      acetyl-, and glutathione transferases, and hydrolases) is reviewed briefly.
      Advances in understanding genetic and environmental factors that influence
      activities of phase I and phase II pathways of drug metabolism are discussed in
      the first sections of this review followed by a consideration of the influence of
      drug metabolism on the actions of agents currently used in the treatment of
      cancer. Emphasis is given to drugs that have recently been introduced into the
      armamentarium of cancer chemotherapy including: inhibitors of chromatin function,
      target-based inhibitors of signal transduction and cyclin-dependent kinases, and
      angiogenesis inhibitors acting on metalloproteinases, epithelial cell growth,
      angiogenesis stimulation, and endothelial-specific integrins.

PMID- 12188891
TI  - The role of the tyrosine kinase inhibitor STI571 in the treatment of cancer.
AB  - The tyrosine kinase inhibitor STI571 exemplifies the successful development of a
      rationally designed, molecularly targeted therapy for the treatment of cancer.
      This review details the steps in the development of this agent and highlights why
      this drug has been so successful in the treatment of chronic myelogenous
      leukaemia. Future directions including the mechanisms and management of
      resistance and new therapeutic strategies are discussed. Finally, the literature
      supporting the use of STI571 in other malignancies, including solid tumors is
      briefly reviewed.

PMID- 12188892
TI  - Structure-based design of novel anticancer agents.
AB  - Recently identified agents that interact with cytoskeletal elements such as
      tubulin include synthetic spiroketal pyrans (SPIKET) and monotetrahydrofuran
      compounds (COBRA compounds). SPIKET compounds target the spongistatin binding
      site of beta-tubulin and COBRA compounds target a unique binding cavity on alpha
      tubulin. At nanomolar concentrations, the SPIKET compound SPIKET-P causes tubulin
      depolymerization and exhibits potent cytotoxic activity against cancer cells.
      COBRA-1 inhibits GTP-induced tubulin polymerization. Treatment of human breast
      cancer and brain tumor cells with COBRA-1 caused destruction of microtubule
      organization and apoptosis. Other studies have identified some promising protein
      tyrosine kinase inhibitors as anti-cancer agents. These include EGFR inhibitors
      such as the quinazoline derivative WHI-P97 and the leflunomide metabolite analog
      LFM-A12. Both LFM-A12 and WHI-P97 inhibit the in vitro invasiveness of EGFR
      positive human breast cancer cells at micromolar concentrations and induce
      apoptotic cell death. Dimethoxyquinazoline compounds WHI-P131 and WHI-P154
      inhibit tyrosine kinase JAK3 in leukemia cells. Of particular interest is WHI
      P131, which inhibits JAK3 but not JAK1, JAK2, SYK, BTK, LYN, or IRK at
      concentrations as high as 350 microM. Studies of BTK inhibitors showed that the
      leflunomide metabolite analog LFM-A13 inhibited BTK in leukemia and lymphoma
      cells. Consistent with the anti-apoptotic function of BTK, treatment of leukemic
      cells with LFM-A13 enhanced their sensitivity to chemotherapy-induced apoptosis.

PMID- 12188893
TI  - Drug target discovery by gene expression analysis: cell cycle genes.
AB  - Gene expression microarrays and gene expression databases provide new
      opportunities for the discovery of drug targets and for determination of a drug's
      mode of action. We review gene expression analysis methods and describe studies
      that have identified cell cycle genes using differential expression analysis and
      co-expression analysis. We present an example of the identification of previously
      unrecognized human cell cycle genes, CDCA1 through CDCA8, that are co-expressed
      with known cell cycle genes including CDC2, CDC7, CDC23, cyclin, MCAK, mki67a,
      topoisomerase II, and others.

PMID- 12188894
TI  - Structural alterations in hereditary dysfibrinogens.
AB  - Dysfibrinogens can be grossly divided in two groups: (1) defective thrombin
      catalyzed conversion of fibrinogen molecules to fibrin monomers, and (2)
      defective fibrin polymerization due to structural alterations in polymerization
      sites, that include "A" and "a" sites, end-to-end D:D abutment surfaces, and
      lateral association sites involving the carboxyl terminal region of the fibrin
      alpha-chain. Recently, a number of mutations in the fibrinogen genes have been
      identified, and many of these encode changes that occur in regions of fibrinogen
      that have been elucidated by high-resolution structural studies. Here we focus on
      the structure-function relationships of fibrinogen that can be inferred from
      studies involving these abnormal molecules.

PMID- 12188895
TI  - Molecular views and measurements of hemostatic processes using atomic force
      microscopy.
AB  - Hemostasis and thrombosis are highly complex and coordinated interfacial
      responses to vascular injury. In recent years, atomic force microscopy (AFM) has
      proven to be a very useful approach for studying hemostatic processes under near
      physiologic conditions. In this report, we review recent progress in the use of
      AFM for studying hemostatic processes, including molecular level visualization of
      plasma proteins, protein aggregation and multimer assembly, and structural and
      morphological details of vascular cells under aqueous conditions. AFM offers
      opportunities for visualizing surface-dependent molecular and cellular
      interactions in three dimensions on a nanoscale and for sensitive, picoNewton
      level, measurements of intermolecular forces. AFM has been used to obtain
      molecular and sub-molecular, resolution of many biological molecules and
      assemblies, including coagulation proteins and cell surfaces. Surface-dependent
      molecular processes including protein adsorption, conformational changes, and
      subsequent interactions with cellular components have been described. This review
      outlines the basic principles and utility of AFM for imaging and force
      measurements, and offers objective perspectives on both the advantages and
      disadvantages. We focus primarily on molecular level events related to hemostasis
      and thrombosis, particularly coagulation proteins, and blood platelets, but also
      explore the use of AFM in force measurements and surface property mapping.

PMID- 12188896
TI  - Dissecting functional interactions in coagulation protein complexes by use of NMR
      spectroscopy.
AB  - The blood coagulation cascade can be considered as a system of well-orchestrated
      protein activation reactions involving and leading to the formation of large
      macromolecular assemblies. NMR investigations performed during the last six years
      have focused on the structural, motional and binding properties of some protein
      domains and interfaces critical for the formation of these protein complexes,
      outlining sophisticated intermolecular adaptations. The studied protein domains
      are either single molecules or covalently-linked heterodimers of the epidermal
      growth factor (EGF) homology domains, calcium-binding EGF domains and gamma
      carboxyglutamic(Gla)-containing domains responsible for calcium-dependent binding
      to cell membranes. The characterized binding interfaces have included those
      between thrombin and fibrinogen, between thrombin and thrombomodulin, between
      factor VIIIa and the cell membrane, between tissue factor and factor VIIa, and
      most recently between factor Va and prothrombin. The obtained results indicate
      that the regulation of blood coagulation by protein and low molecular weight
      cofactors may involve a significant degree of protein folding transitions with
      changes in molecular and conformational motions coupled to enzymatic activities.
      This new level of complexity of the molecular processes controlling coagulation
      may lead to novel strategies for the development of more effective therapeutic
      anticoagulants.

PMID- 12188897
TI  - Structure, function, and activation of coagulation factor VII.
AB  - Factor VII is the coagulation protease responsible for starting a cascade of
      proteolytic events that lead to thrombin generation, fibrin deposition, and
      platelet activation. As such, FVII has attracted wide interest as a target for
      clinical anti-coagulant applications. Commensurate with the critical importance
      of maintaining balance between thrombosis and hemostasis and its place at the
      beginning of the coagulation process, FVII is subject to a variety of biological
      and biochemical control mechanisms, among them allosteric influences exerted by
      cofactors, substrates, and inhibitors. Sites on FVIIa where allosteric influences
      are exerted and manifested have been identified and characterized in considerable
      detail. In recent years, a three-dimensional context for the interpretation of
      these results has become available from structural studies. New X-ray structures
      have augmented specific aspects of our understanding, in particular the X-ray
      structure of a fragment of the FVII zymogen. This review summarizes general
      allosteric behaviors of FVIIa and recapitulates structural findings since 1996,
      with particular emphasis on the recently determined zymogen structure.

PMID- 12188898
TI  - Structure and function of the von Willebrand factor A1 domain.
AB  - The role of von Willebrand factor (VWF) in blocking hemorrhage is centered on its
      ability to act as a bridging adhesive molecule between platelets and components
      of the extracellular matrix or other platelets. In the course of chronic vascular
      diseases, moreover, the same properties of VWF may become the cause of
      pathological thrombus formation leading to arterial occlusion. There is
      convincing evidence that VWF functions involving interactions with platelets
      ultimately depend on binding to the membrane glycoprotein (GP) Ibalpha receptor
      mediated by the A1 domain. In this review, we present the current knowledge on
      the structural features of the VWF A1 domain that support its functions.

PMID- 12188899
TI  - New insights into binding interfaces of coagulation factors V and VIII and their
      homologues lessons from high resolution crystal structures.
AB  - The large, multifunctional proteins Factors V and VIII are cofactors in the
      coagulation cascade and possess a similar domain structure, A1-A2-B-A3-C1-C2. The
      C domains are related to the discoidin protein family, while the A domains are
      homologous to the copper-binding protein ceruloplasmin. After proteolytic
      activation, Factors V and VIII behave as peripheral membrane proteins, binding to
      negatively charged membranes containing phosphatidylserine, primarily via
      specific sites on their C2 domains. This type of membrane surface is exposed at
      sites of tissue damage, where platelets have become activated. The cofactors then
      accelerate sequential proteolytic activations that occur at critical control
      points in the blood coagulation cascade via complex formation with specific
      serine proteinases. Here we compare recent structural and functional studies of
      the C2 domains of Factors V and VIII, and discuss their respective roles. The
      membrane-binding motifs consist of several exposed hydrophobic side chains
      surrounded by a ring of basic residues, and the C2 domains appear poised to
      insert their hydrophobic "feet" into the membrane interior as basic residues
      interact favorably with phosphatidylserine head groups. In line with their
      physiological roles, the membrane-binding surfaces of the C2 domains display a
      good deal of mobility. We then extend our analysis to other members of the
      discoidin protein family, which perform diverse physiological functions involving
      signaling pathways at cell surfaces. Finally, structural similarities between
      discoidin proteins and the topologically distinct but functionally related
      membrane-binding "classic C2 domains", including signal-transduction proteins
      such as Protein Kinase C and phospholipases, are noted.

PMID- 12188900
TI  - Structural bioinformatics: methods, concepts and applications to blood
      coagulation proteins.
AB  - Structural and theoretical analyses of proteins are central to the understanding
      of complex molecular mechanisms and are fundamental to the drug discovery
      process. Computational techniques yield useful insights into an ever-wider range
      of biomolecular systems. Protein three-dimensional structures and molecular
      functions can be predicted in some circumstances, while experimental structures
      can be analyzed in depth via such computational approaches. Non-covalent binding
      of biomolecules can be understood by considering structural, thermodynamic and
      kinetic issues, and theoretical simulations of such events can be attempted. The
      central role of electrostatic interactions with regard to protein function,
      structure and stability has been investigated and some electrostatic properties
      can be modeled theoretically. Computer methods thus help to prioritize, design,
      analyze and rationalize biochemical experiments. Cardiovascular diseases and
      associated blood coagulation disorders are leading causes of death worldwide.
      Blood coagulation involves more than 30 proteins that interact specifically with
      various degrees of affinity. Many of these molecules can also bind transiently to
      phospholipid surfaces. Numerous point mutations in the genes of coagulation
      proteins and regulators have been identified. Understanding the coagulation
      cascade, its regulation and the impact of mutations is required for the
      development of new therapies and diagnostic tools. In this review, we describe
      concepts and methods pertaining to the field of structural bioinformatics. We
      provide examples of applications of these approaches to blood coagulation
      proteins and show that such studies can give insights about molecular mechanisms
      contributing to cardiovascular disease susceptibility.

PMID- 12188901
TI  - Substrate mimetics in protease catalysis: characteristics, kinetics, and
      synthetic utility.
AB  - This article reviews the latest developments in protease-catalyzed peptide
      synthesis focusing on the use of substrate mimetics. The substrate mimetics
      approach takes advantage of the characteristic of this novel type of substrates
      to direct the enzyme to recognize an alternative site on the acyl donor, i.e. the
      site-specific ester leaving group, mediating the acceptance of originally poorly
      reactive acyl moieties. At first the kinetics and catalytic mechanism of
      substrate mimetics-mediated reactions are discussed on the basis of hydrolysis,
      peptide synthesis, protein-ligand docking, and molecular dynamics studies. By the
      example of the Glu-specific V8 protease and the aromatic amino acid-specific
      chymotrypsin both the empirical and computer-aided design of specific substrate
      mimetics is described. The influence of the leaving group specifically recognized
      by the enzyme is also considered. The benefits of these artificial substrates
      over common acyl donor components are illustrated by selected synthesis reactions
      of small peptides, peptide isosteres, non-peptidic carboxylic acid amides, and
      the coupling of peptide fragments at non-specific ligation sites resulting in
      biologically active peptide products. Finally, this review focuses on critical
      syntheses that uses specific-amino acid-containing peptides as the reactants of
      ligation. Based on these, the restrictions of the substrate mimetics approach is
      critically discussed and techniques to their overcoming are presented.

PMID- 12188902
TI  - Mass spectrometry: an emerging alternative to traditional methods for measurement
      of diagnostic proteins, peptides and amino acids.
AB  - Novel approaches to protein measurement based on mass spectrometry are being
      developed that challenge more traditional methods. This review summarizes the
      emergence of mass spectrometry as a tool for clinical protein, peptide, and amino
      acid determination. Specific applications of mass spectrometry to the measurement
      of transferrin, transthyretin, glycated hemoglobin, and homocysteine will be
      discussed, as will the limitations of the technology, and future directions for
      clinical protein measurement.

PMID- 12188903
TI  - Alpha-helix and beta-hairpin Folding from experiment, analytical theory and
      molecular dynamics simulations.
AB  - The alpha-helix and beta-hairpin are the minimal secondary structure elements of
      proteins. Identification of the factors governing the formation of these
      structures independently of the rest of the protein is important for
      understanding the determinants and rules driving the folding process to a unique
      native structure. It has been shown that some alpha-helices and beta-hairpins can
      fold autonomously into native-like structures, either in aqueous solution or in
      the presence of an organic co-solvent; possible mechanisms of these processes
      have been considered in literature. The characteristic times for folding of alpha
      and beta structures are estimated from experiments, simple analytical theories
      and more detailed computer models. Our aim is to review recent experimental and
      theoretical studies of folding of alpha and beta structures focusing much
      attention on beta-hairpins.

PMID- 12188904
TI  - The prediction of amphiphilic alpha-helices.
AB  - A number of sequence-based analyses have been developed to identify protein
      segments, which are able to form membrane interactive amphiphilic alpha-helices.
      Earlier techniques attempted to detect the characteristic periodicity in
      hydrophobic amino acid residues shown by these structure and included the
      Molecular Hydrophobic Potential (MHP), which represents the hydrophobicity of
      amino acid residues as lines of isopotential around the alpha-helix and analyses
      based on Fourier transforms. These latter analyses compare the periodicity of
      hydrophobic residues in a putative alpha-helical sequence with that of a test
      mathematical function to provide a measure of amphiphilicity using either the
      Amphipathic Index or the Hydrophobic Moment. More recently, the introduction of
      computational procedures based on techniques such as hydropathy analysis,
      homology modelling, multiple sequence alignments and neural networks has led to
      the prediction of transmembrane alpha-helices with accuracies of the order of 95%
      and transmembrane protein topology with accuracies greater than 75%. Statistical
      approaches to transmembrane protein modeling such as hidden Markov models have
      increased these prediction levels to an even higher level. Here, we review a
      number of these predictive techniques and consider problems associated with their
      use in the prediction of structure / function relationships, using alpha-helices
      from G-coupled protein receptors, penicillin binding proteins, apolipoproteins,
      peptide hormones, lytic peptides and tilted peptides as examples.

PMID- 12188905
TI  - Cold adaptation of archaeal elongation factor 2 (EF-2) proteins.
AB  - Cell growth at low temperature is dependent on the ability of cells to perform
      protein synthesis. Cold adapted micro-organisms (psychrophilic or
      psychrotolerant) have a superior ability to perform translation at low
      temperature. This review addresses cold adaptation of protein synthesis in
      Archaea by examining what is presently known about thermal adaptation of
      elongation factor 2 (EF-2) proteins from Archaea. Despite the knowledge that
      Archaea are abundant in cold environments (e.g. the ocean), few cold adapted
      species have been isolated and studied. As a result this review is largely
      confined to comparative analyses of EF-2 proteins from psychrotolerant
      (Methanococcoides burtonii) and thermophilic (Methanosarcina thermophila)
      methanogens. A key finding from these studies is that in addition to inherent
      properties of the EF-2 proteins, intracellular factors (e.g. ribosomes and
      intracellular solutes) play a central role in thermal adaptation.

PMID- 12188906
TI  - Novel cysteine proteinase inhibitors homologous to the proregions of cysteine
      proteinases.
AB  - Propeptides of papain-like cysteine proteinases such as papain, cathepsins B, L
      and S are potent inhibitors of their cognate cysteine proteinases with Ki values
      in the nanomolar range, and they exhibit highest inhibition selectivity for
      enzymes from which they originate. Recent studies have identified novel inhibitor
      proteins that are homologous to the proregions of papain-like cysteine
      proteinases. Mouse activated T-lymphocytes express cytotoxic T-lymphocyte antigen
      (CTLA-2), which is homologous to the proregion of mouse cathepsin L. CTLA-2
      exhibits inhibitory activities to several cysteine proteinases. We have also
      identified a similar propeptide-like cysteine proteinase inhibitor, Bombyx
      cysteine proteinase inhibitor (BCPI), in the silkmoth Bombyx mori. BCPI is a slow
      and tight binding inhibitor of cathepsin L-like cysteine proteinases with Ki
      values in picomolar range, and the inhibition is highly selective towards these
      proteinases just like the propeptides. Recent genome analyses have shown the
      expression of similar propeptide-like proteins in Drosophila and rat, suggesting
      the presence of a novel class of cysteine proteinase inhibitors in a variety of
      organisms. Studies of the gene structures and phylogenetic analysis have shown
      that genes of the propeptide-like cysteine proteinase inhibitors have emerged
      from ancestor genes of their parental enzymes.

PMID- 12188907
TI  - Insulin-like growth factor receptor-1 as an anti-cancer target: blocking
      transformation and inducing apoptosis.
AB  - IGF-IR (Insulin-like growth factor receptor 1) is a tetrameric glycoprotein
      composed of two alpha and two beta subunits. The alpha subunit localizes extra
      cellularly for ligand binding, whereas the beta subunit consists of transmembrane
      chains and a cytoplasmic tyrosine kinase domain for enzymatic activity. IGF-IR
      ligands, IGF-I and IGF-II, are mitogens and survival factors for many cancer
      cells. Binding of ligands to the IGF-IR initiates a cascade of events leading to
      activation of signal transduction pathways, mainly MAPK and PI-3K pathways, to
      stimulate proliferation/mitogenesis, to induce neoplastic transformation, to
      inhibit apoptosis, and to promote angiogenesis and metastasis. It has been shown
      that the presence of IGF-IR was required for transformation induced by many
      oncogenes and over-expression or constitutive activation of IGF-IR gave rise to
      transformed phenotypes. Significantly, over-expression of IGF-IR was observed in
      multiple human cancers including carcinomas of breast, lung, colon, and prostate.
      Patients with IGF-IR positive cancers had a worse prognosis in some cases.
      Furthermore, down-regulation or functional inactivation of IGF-IR sensitized
      tumor cells to apoptosis and reversed tumor cell phenotype. Thus, IGF-IR appears
      to be a promising cancer target. Indeed, a variety of approaches aimed at
      targeting IGF-IR have been utilized to prove the concept, or are being developed
      for potential anticancer therapies. These include targeting functional IGF-IR on
      cell surface, targeting ligand/receptor interaction, targeting receptor
      expression and functions, and targeting receptor kinase activity. Cancer patients
      could eventually benefit from the development of these specific IGF-IR
      antagonists.

PMID- 12188908
TI  - Cancer-targeted polymeric drugs.
AB  - A major challenge in cancer chemotherapy is the selective delivery of small
      molecule anti cancer agents to tumor cells. Water-soluble polymer-drug conjugates
      exhibit good water solubility, increased half-life, and potent anti tumor
      effects. By localizing the drug at the desired site of action, macromolecular
      therapeutics have improved efficacy and enhanced safety at lower doses. Since
      small molecule drugs and macromolecular drugs enter cells by different pathways,
      multi-drug resistance (MDR) can be minimized. Anti-cancer polymer-drug conjugates
      can be divided into two targeting modalities: passive and active. Tumor tissues
      have anatomic characteristics that differ from normal tissues. Macromolecules
      penetrate and accumulate preferentially in tumors relative to normal tissues,
      leading to extended pharmacological effects. This "enhanced permeability and
      retention" (EPR) effect is the principal reason for current successes with
      macromolecular anti-cancer drugs. Both natural and synthetic polymers have been
      used as drug carriers, and several bioconjugates have been clinically approved or
      are in human clinical trials. While clinically useful anti-tumor activity has
      been achieved using passive macromolecular drug delivery systems, further
      selectivity is possible by active targeting. Attachment of targeting moieties to
      the polymer backbone can further exploit differences between cancer and normal
      cells through selective receptor-mediated endocytosis. This strategy would
      augment the EPR effect, thereby further improving the therapeutic index of the
      macromolecular drug. This review discusses the development and therapeutic
      potential of prototype macromolecular drugs for use in cancer chemotherapy.
      Specific examples are selected to illustrate the basic design principles for
      soluble polymeric drug delivery systems.

PMID- 12188909
TI  - Cancer therapy with beta-lapachone.
AB  - Beta-lapachone is an ortho naphthoquinone, originally isolated from a tree whose
      extract has been used medicinally for centuries. Recent investigations suggest
      its potential application against numerous diseases. Its lethality at micromolar
      ( m) concentrations against a variety of cancer cells in culture indicates its
      potential against tumor growth. A few experiments with positive results have been
      performed that apply the compound to tumors growing in animals. Particularly
      promising is the remarkably powerful synergistic lethality between beta-lapachone
      and taxol against several tumor cell lines implanted into mice; the mice did not
      appear to be adversely affected. Enhanced lethality of X-rays and alkylating
      agents to tumor cells in culture was reported when beta-lapachone was applied
      during the recovery period, because of inhibition of DNA lesion repair. Clinical
      trials are still to be initiated. The detailed mechanism of cell death induced by
      beta-lapachone remains for investigation. DNA topoisomerase I was the first
      biochemical target of beta-lapachone to be discovered, although its role in cell
      death is not clear. A proposed mechanism of cell death is via activation of a
      futile cycling of the drug by the cytoplasmic two-electron reductase NAD(P) H:
      quinone oxidoreductase, also known as NQO1, DT-diaphorase and Xip3. Death of NQO1
      expressing cells is prevented by the NQO1 inhibitor dicoumarol, and cells with
      low NQO1 are resistant. At higher drug concentrations the production of reactive
      oxygen species (ROS) appears to be responsible. Furthermore, this process is p53-
      and caspase- independent. Either apoptotic or necrotic cell death can result, as
      reported in various studies performed under differing conditions. Beta-lapachone
      is one of a few novel anticancer drugs currently under active investigation, and
      it shows promise for chemotherapy alone and especially in combinations.

PMID- 12188910
TI  - Pharmacogenomics opportunities in nuclear receptor targeted cancer therapy.
AB  - Nuclear Hormone Receptors (NR) represent one of the most promising protein
      families in terms of therapeutic applications. These transcription factors are
      naturally switched on and off by small molecule hormones presenting physico
      chemical properties very similar to therapeutic chemical entities. NRs represent
      therefore intrinsically a very good family of protein targets for the prevention
      and treatment of diverse diseases, including cancer. Several known anti-cancer
      drugs, such as tamoxifen or flutamide, are targeting NRs, and many more are
      expected to reach market. The detailed knowledge of the structural mechanism
      underlying activation and inhibition of NRs by small molecule modulators begets
      important therapeutic opportunities. The crystal structure of at least nine NR
      ligand binding domains (LBDs) revealed at the atomic level how natural or
      synthetic agonists and antagonists can promote recruitment of co-activator and co
      repressor proteins. Interestingly, it was recently shown that nucleotide
      polymorphisms located in NR LBDs could alter or even reverse the response of the
      receptors to small molecule ligands. Mapping these polymorphisms on the structure
      of the LBD can reveal why agonists or antagonists become inactive against the
      mutated receptor, allow atomic models for resistance to cancer therapy, and open
      the door to the rational design of improved anti-cancer drugs, customized for
      each patient.

PMID- 12188911
TI  - Examining the relationship between cancer invasion/metastasis and drug
      resistance.
AB  - Studies of cancer invasion/metastasis and drug resistance have in the past
      generally proceeded along the separate pathways of research. Recently, however,
      interest has been focused on the possible relationship between drug resistance
      and cancer invasion and metastasis. A relationship between these two phenotypes
      has been demonstrated by two types of observation: firstly, some tumor cells
      selected for resistance to drugs are more invasive/metastatic relative to non
      resistant parental cells; secondly, in some cases, secondary (more metastatic)
      tumors are more resistant to chemotherapeutic drugs than their primary
      counterparts. In other instances reported in the literature, no correlation is
      seen between drug exposure/resistance and cancer invasion/metastasis. The
      possibility that treatment with some chemotherapeutic drugs may be able to
      promote cancer invasion and metastasis needs further investigation because of its
      potential clinical relevance. A better understanding of any relationship between
      drug resistance and cancer invasion could lead to more effective cancer
      treatment.

PMID- 12188912
TI  - Mutant epidermal growth factor receptors as targets for cancer therapy.
AB  - The epidermal growth factor (EGF) receptor is overexpressed in many cancers, and
      is under intensive investigation as a target for cancer therapy. Cancer cells
      have also been shown to express mutated EGF receptors; these are potentially
      highly specific targets for cancer therapeutics, as they have not been detected
      in any normal adult tissues. The most common of these mutant EGF receptors,
      EGFRvIII, is one in which amino acids 6 - 273 of the extracellular domain are
      deleted. This specific mutation is common in glioblastoma and in several other
      types of cancer, and has been shown to promote aggressive growth of tumors in
      vivo. The loss of part of the extracellular domain results in a receptor that has
      constitutive tyrosine kinase activity. Current evidence suggests that EGFRvIII
      has altered signalling properties compared to normal EGF receptor. The mutation
      in EGFRvIII also creates a new, cancer cell-specific epitope. This epitope is
      extracellular and therefore represents a very promising target for antibody
      directed therapeutics. This review covers our current understanding of the
      properties of EGFRvIII, and recent developments in the characterization and
      therapeutic application of EGFRvIII-specific antibodies.

PMID- 12188913
TI  - Pharmacology of topoisomerase I inhibitors irinotecan (CPT-11) and topotecan.
AB  - Topotecan and irinotecan (CPT-11) are both anticancer agents active in the
      inhibition of topoisomerase I, an enzyme involved in DNA replication and RNA
      transcription. During the last decades, an immense amount of research into this
      class of anticancer agents has been conducted, the positive results of which led
      to the clinical use of topotecan and CPT-11 in ovarian cancer and colorectal
      cancer, respectively. Here, we review the currently most important pharmacologic
      aspects of these drugs, including their mechanisms of action, metabolism,
      activity- and toxicity-profiles and mechanisms of resistance, to provide a global
      insight into their pharmacology. We also discuss the effects of combinations with
      other anticancer agents, which have been tested for synergistic antitumor
      effects. Pharmacokinetic and pharmacodynamic biomodulation, to enhance the
      bioavailability of the active anticancer agent or to reduce drug related
      toxicities have currently reached clinical application. As pharmacogenetics
      enters the clinical stage, this will lead to more "fine-tuning" in anticancer
      treatment (for instance by individualized dosing). The clarification of the
      mechanisms of action and resistance of topotecan and CPT-11 should enable us to
      understand their pharmacological behavior even better and might lead to the
      development of more potent camptothecin-derivatives in the future.

PMID- 12188914
TI  - Protein kinase C-theta (PKCtheta), a potential drug target for therapeutic
      intervention with human T cell leukemias.
AB  - The link between apoptosis and malignant cell growth is firmly established, and
      various forms of therapy in cancer, e.g., the use of DNA-damaging
      chemotherapeutic drugs, are based on the principle of inducing apoptosis in
      malignant cells. However, in many known instances, tumor cells develop resistance
      to apoptosis through various mechanisms. Thus, interventions designed to
      facilitate tumor cells apoptosis are likely to have a therapeutic benefit.
      PKCtheta, which is expressed relatively selectively in T cells, plays an
      important role in mature T cell activation and proliferation upon its
      translocation to the plasma membrane. PKCtheta is necessary for induction of the
      interleukin-2 (IL-2) gene because the transcription factors AP-1 and NF-kappaB,
      which are essential for IL-2 gene promoter activation, are main targets of
      PKCtheta. Recent studies revealed that PKCtheta provides an important survival
      signal that protects leukemic T cells from Fas- or UV-induced apoptosis. These
      findings and the constitutive localization of PKCq in the membrane of some
      leukemic T cells suggests that it plays a role in leukemic T cell survival and/or
      proliferation, and that selective PKCtheta-inhibitory strategies may facilitate
      elimination of malignant T cells. The high-affinity IL-2 receptor (IL-2Ralpha) is
      a major target of receptor-directed therapy in several human diseases, and it is
      constitutively expressed by the malignant cells in some T cell leukemias,
      suggesting an autocrine IL-2/IL-2R loop that participates in the expansion of
      leukemic IL-2R(+) cells. Therefore, given the essential role of PKCtheta in IL-2
      production, IL-2 gene regulation by PKCtheta could also be of therapeutic
      interest.

PMID- 12188915
TI  - Clinical development of angiogenesis inhibitors to vascular endothelial growth
      factor and its receptors as cancer therapeutics.
AB  - Angiogenesis, the formation of new blood vessels, is essential for both tumor
      growth and metastasis. Recent advances in our understanding of the molecular
      mechanisms underlying the angiogenesis process and its regulation have led to the
      discovery of a variety of pharmaceutical agents with anti-angiogenic activity.
      The potential application of these angiogenesis inhibitors is currently under
      intense clinical investigation. Compelling evidence suggests that vascular
      endothelial growth factor (VEGF) and its receptors play critical roles in tumor
      associated angiogenesis, and that they represent potential targets for
      therapeutic intervention. This has been demonstrated in a variety of animal tumor
      models in which disabling the function of VEGF and its receptors was shown to
      inhibit both tumor growth and metastasis. A number of agents designed
      specifically for targeting VEGF and/or its receptors are being evaluated in
      various clinical trials in cancer patients. This review will discuss the biology
      of the VEGF and its receptors, the mechanisms of action as well as the current
      status in clinical development of antagonistic agents to VEGF and its receptors.
      Included in this review are antagonistic antibodies, ribozymes, immunotoxins, and
      synthetic small molecular inhibitors.

PMID- 12188916
TI  - Chromatin (dis)organization and cancer: BUR-binding proteins as biomarkers for
      cancer.
AB  - Malignant transformation of cells is associated with changes in gene expression.
      Gross alterations in chromatin organization may be involved in such gene
      dysregulation, as well as the involvement of specific transcription factors.
      Specialized genomic DNA segments that exhibit high affinity to the nuclear matrix
      in vitro have been designated as matrix/scaffold attachment regions (MARs/SARs).
      MARs are postulated to anchor chromatin onto the nuclear matrix, thereby
      organizing genomic DNA into topologically distinct loop domains that are
      important in replication and transcription. In support of this notion, MARs often
      colocalize or exist in close proximity to regulatory sequences including
      enhancers. Base unpairing regions (BURs) are typically 100-150 bp regions within
      MARs, possess an intrinsic propensity to unwind under negative superhelical
      strain, and are considered to be hallmark of MARs. To investigate a potential
      mechanism that could lead to significant alterations in gene expression in cancer
      cells, this review focuses on a group of chromatin-associated proteins that
      specifically recognize double stranded BURs. Several important proteins have been
      identified from cancer cells as BUR-binding proteins, including poly (ADP-ribose)
      polymerase (PARP-1), Ku autoantigen, SAF-A, HMG-I(Y), nucleolin and p53. Many of
      these proteins are dramatically upregulated in malignancy of the breast. Increase
      in the amount of these BUR-binding proteins, some of which are known to interact
      with each other, may not only provide an architectural core but also recruit
      functional multi-molecular complexes at the base of chromatin loops to affect
      multiple distant genes. Experimental strategies by which these proteins can be
      exploited as carcinoma-specific diagnostic markers and as targets for
      antineoplastic therapy are discussed.

PMID- 12188917
TI  - Prospects for anti-neoplastic therapies based on telomere biology.
AB  - The maintenance of specialized nucleoprotein structures at the ends of human
      chromosomes called telomeres is essential for chromosome stability, and plays a
      fundamental role in the regulation of cellular lifespan. Without new synthesis of
      telomeres, chromosome ends shorten with progressive cell division, eventually
      triggering either replicative senescence or apoptosis when telomere length
      becomes critically short. The regulation of telomerase activity in human cells
      plays a significant role in the development of cancer. Telomerase is tightly
      repressed in the vast majority of normal human somatic cells but becomes
      activated during cell immortalization and in cancers. Recent work has
      demonstrated that inhibiting or targeting telomerase shows promise as a novel
      anti-neoplastic strategy; however, the biology of telomeres and telomerase
      predict that such approaches will differ in important ways from traditional
      cytotoxic drug therapies. Understanding telomerase biology may eventually lead to
      several types of clinically effective, telomerase-based therapies for neoplastic
      disease.

PMID- 12188918
TI  - Diphtheria fusion protein therapy of chemoresistant malignancies.
AB  - Patients with widespread cancer respond initially to combination chemotherapy,
      immunotherapy, and/or radiotherapy, but most relapse with chemoresistant disease.
      Novel methods of killing resistant neoplastic stem cells are needed. One such
      approach is therapy with targeted toxins composed of tumor cell selective ligands
      covalently linked to group I peptide toxins (group II and III peptide toxins act
      on the cell surface). The targeted toxin is delivered to the cell by a tumor
      selective ligand. Once bound, the ligand-receptor complex is internalized. The
      catalytic domain escapes to the cytosol. The toxin then enzymatically modifies a
      critical cell function (protein synthesis, p21 Rho activity, protein kinase
      signaling, cyclic AMP signaling or others). The irreversibly damaged cells fails
      to divide and, eventually, undergoes lysis or programmed cell death. Targeted
      peptide toxins used to date in the treatment of chemotherapy refractory cancers
      include ricin toxin, Pseudomonas exotoxin, pokeweed antiviral protein, saporin,
      gelonin and diphtheria toxin. In this review, we have focused on the applications
      of genetically engineered diphtheria toxin for cancer therapy.

PMID- 12188919
TI  - Integrins as novel drug targets for overcoming innate drug resistance.
AB  - Acquired drug resistance continues to be one of the major obstacles hindering the
      successful treatment of many forms of cancer. Compounds utilized as antagonists
      of these cytoprotective mechanisms have, for the most part, proven to be
      ineffective at overcoming clinical resistance to cytotoxic drugs. Recently, the
      tumor cell microenvironment has been found to have a significant bearing on the
      survival of tumor cells following exposure to a wide variety of anti-neoplastic
      agents, prior to the acquisition of known drug resistance mechanisms.
      Specifically, interactions between cell surface integrins and extracellular
      matrix components have been shown to be responsible for this phenomenon of innate
      drug resistance, which we have termed Cell Adhesion Mediated Drug Resistance, or
      CAM-DR. Following its discovery using a multiple myeloma cell line model,
      evidence for CAM-DR has been found in a multitude of other human tumor cell
      types. In contrast to many other drug resistance mechanisms, integrin-mediated
      cell signaling is capable of protecting against death induced by an extremely
      wide variety of structurally and functionally diverse agents from traditional DNA
      damaging agents to the promising novel kinase inhibitor STI-571. This review
      examines the role of integrins in regard to their ability to protect tumor cells
      from drug- and radiation-induced apoptosis through numerous intracellular
      mechanisms. Current and future antagonists of specific integrin heterodimers may
      have the potential to sensitize tumor cells when used in combination with
      standard chemotherapy regimens. Specific signal transduction pathways initiated
      by integrin ligation will also be discussed as potential bridge points for
      inhibiting cell survival during cytotoxic drug exposure.

PMID- 12188920
TI  - WT1 as a novel target antigen for cancer immunotherapy.
AB  - Wild-type Wilms' tumor gene WT1 is expressed at high levels not only in most of
      acute myelocytic, acute lymphocytic, and chronic myelocytic leukemia, but also in
      various types of solid tumors including lung cancer. We tested the ability of the
      gene product (WT1) to serve as a target antigen for tumor  specific immunotherapy
      both in human in vitro system and mouse in vivo system. In the latter, we can
      evaluate the efficacy and the side effects of WT1 vaccination in vivo. In the
      human in vitro system, two WT1 peptides that contain HLA-A2.1 binding anchor
      motifs were determined to bind to HLA-A2.1 molecules. Peripheral blood
      mononuclear cells (PBMC) from an HLA-A2.1-psitive donor were repeatedly
      stimulated in vitro with TAP-deficient T2 cells pulsed with each of these two
      peptides, and CD8-positive cytotoxic T lymphocytes (CTLs) that specifically lyse
      WT1-expressing, HLA-A2.1-positive tumor cells were induced. Other groups also
      have succeeded in generating CTLs which specifically lyse WT1-expressing leukemia
      cells, and which do not inhibit colony-formation of normal hematopoietic cells
      that express WT1 at physiological levels. In the mouse in vivo system,
      immunization of C57BL/6 mice with one WT1 peptide with relatively high binding
      affinity for H-2D(b) molecules, which contain H-2D(b) binding anchor motifs,
      induced CTLs, which specifically lysed WT1-expressing tumor cells in an H-2D(b)
      restricted manner. Furthermore, mice immunized with the WT1 peptide (peptide
      vaccination) or WT1 cDNA (DNA vaccination) rejected challenges by WT1-expressing
      tumor cells and survived with no signs of auto-aggression to WT1-expressing
      normal organs by the induced CTLs. The WT1 protein has been identified as a novel
      tumor antigen and recent investigations provide a rationale for developing WT1
      based adoptive T cell therapy and vaccination against various kinds of malignant
      neoplasms.

PMID- 12188921
TI  - Sulfonamides and sulfonylated derivatives as anticancer agents.
AB  - The sulfonamides constitute an important class of drugs, with several types of
      pharmacological agents possessing antibacterial, anti-carbonic anhydrase,
      diuretic, hypoglycemic and antithyroid activity among others. A host of
      structurally novel sulfonamide derivatives have recently been reported to show
      substantial antitumor activity in vitro and/or in vivo. Although they have a
      common chemical motif of aromatic/heterocyclic sulfonamide, there are a variety
      of mechanisms of their antitumor action, such as carbonic anhydrase inhibition,
      cell cycle arrest in the G1 phase, disruption of microtubule assembly, functional
      suppression of the transcriptional activator NF-Y, and angiogenesis (matrix
      metalloproteinase, MMP) inhibition among others. Some of these compounds selected
      via elaborate preclinical screenings or obtained based on computer-aided drug
      design, are currently being evaluated in clinical trials. This review summarizes
      recent classes of sulfonamides and related sulfonyl derivatives disclosed
      ultimately as effective tumor cell growth inhibitors, or for the treatment of
      different types of cancer.

PMID- 12188922
TI  - Receptor selective synthetic retinoids as potential cancer chemotherapy agents.
AB  - For many years, the vitamin A metabolite retinoic acid (RA) has been known to
      have profound effects on development, cellular proliferation and differentiation,
      and tumor growth and invasion. The wide-ranging effects of RA on cellular
      proliferation and migration have made it a useful chemotherapeutic agent in the
      treatment of many types of cancer. In the last fifteen years, with the discovery
      of nuclear receptors for RA, the molecular basis for the effects of this molecule
      has become apparent. Retinoic acid receptors (RAR) are members of a superfamily
      of ligand dependent transcription factors that interact with an increasingly
      large array of coactivators and repressors to regulate target gene expression
      through binding to cognate recognition sequences in the promoters of these genes.
      Alterations in RAR expression and function have been demonstrated in many types
      of cancer. The translocation of RARalpha with PML or PLZF genes in acute
      promyelocytic leukemia is a paradigm of the role of RARs in cancer biology. In
      addition, the development of receptor selective synthetic retinoids has greatly
      expanded our knowledge of RAR function in tumor cells and provided additional
      treatment options for cancer patients. This review will examine the development
      of receptor selective retinoids, their uses to date, and future potential.

PMID- 12188923
TI  - Transcriptional regulation of the rat type IIA phospholipase A2 gene by cAMP and
      interleukin-1beta in vascular smooth muscle cells: interplay of the
      CCAAT/enhancer binding protein (C/EBP), nuclear factor-kappaB and Ets
      transcription factors.
AB  - The abundant secretion of type IIA secreted phospholipase A(2) (sPLA(2)) is a
      major feature of the inflammatory process of atherosclerosis. sPLA(2) is crucial
      for the development of inflammation, as it catalyses the production of lipid
      mediators and induces the proliferation of smooth muscle cells. We have analysed
      the activation of sPLA(2) transcription by cAMP and interleukin-1beta (IL-1beta),
      and shown that the 500 bp region upstream of the transcription start site of the
      rat sPLA(2) gene is implicated in activation by synergistically acting cAMP and
      IL-1beta. We transiently transfected and stimulated rat smooth muscle cells in
      primary culture and measured the promoter activities of serial and site-directed
      deletion mutants of sPLA(2)-luciferase constructs. A distal region, between -488
      and -157 bp, bearing a CAAT/enhancer binding protein (C/EBP)-responsive element (
      242 to -223) was sufficient for cAMP/protein kinase A-mediated sPLA(2) promoter
      activation. We find evidence for the first time that activation of the sPLA(2)
      promoter by IL-1beta requires activation of an Ets-responsive element in the -184
      to -180 region of the distal promoter via the Ras pathway and a nuclear factor
      kappaB site at positions -141 to -131 of the proximal promoter. We also used
      electrophoretic mobility shift assays to identify five binding sites for the Sp1
      factor; a specific inhibitor of Sp1, mithramycin A, showed that this factor is
      crucial for the basal activity of the sPLA(2) promoter.

PMID- 12188924
TI  - A potential role for nuclear factor of activated T-cells in receptor tyrosine
      kinase and G-protein-coupled receptor agonist-induced cell proliferation.
AB  - We have studied the role of nuclear factor of activated T-cells (NFAT)
      transcription factors in the induction of vascular smooth muscle cell (VSMC)
      growth by platelet-derived growth factor-BB (PDGF-BB) and thrombin, the receptor
      tyrosine kinase (RTK) and G-protein-coupled receptor (GPCR) agonists,
      respectively. NFATc1 but not NFATc2 or NFATc3 was translocated from the cytoplasm
      to the nucleus upon treatment of VSMCs with PDGF-BB or thrombin. Translocation of
      NFATc1 was followed by an increase in NFAT-DNA binding activity and NFAT
      dependent reporter gene expression. Cyclosporin A (CsA), a potent and specific
      inhibitor of calcineurin, a calcium/calmodulin-dependent serine phosphatase
      involved in the dephosphorylation and activation of NFATs, blocked NFAT-DNA
      binding activity and NFAT-dependent reporter gene expression induced by PDGF-BB
      and thrombin. CsA also completely inhibited PDGF-BB- and thrombin-induced VSMC
      growth, as measured by DNA synthesis and cell number. In addition, forced
      expression of the NFAT-competing peptide VIVIT for calcineurin binding
      significantly attenuated the DNA synthesis induced by PDGF-BB and thrombin in
      VSMCs. Together, these findings for the first time demonstrate a role for NFATs
      in RTK and GPCR agonist-induced growth in VSMCs.

PMID- 12188926
TI  - Posidonia oceanica meadow: a low nutrient high chlorophyll (LNHC) system?
AB  - BACKGROUND: In spite of very low nutrient concentrations in its vicinity - both
      column and pore waters-, the Posidonia oceanica of the Revellata Bay displays
      high biomass and productivity. We measured the nutrient fluxes from the sediment
      into the water enclosed among the leaf shoots ("canopy water") to determine if it
      is possible source of nutrients for P. oceanica leaves. RESULTS: During the
      summer, the canopy water appears to act as a nutrient reservoir for the plant.
      During that period, the canopy water layer displays both a temperature 0.5
      degrees C cooler than the upper water column, and a much higher nutrient content,
      as shown in this work using a very simple original technique permitting to sample
      water with a minimal disturbance of the water column's vertical structure.
      Despite low nutrient concentrations in pore water, mean net fluxes were measured
      from the sediment to the canopy water. These fluxes are sufficient to provide 20%
      of the mean daily nitrogen and phosphorus requirement of the P. oceanica shoots.
      CONCLUSION: An internal cycling of nutrients from P. oceanica senescent leaves
      was previously noted as an efficient strategy to help face low nutrient
      availability. The present study points out a second strategy which consists in
      holding back, in the canopy, the nutrients released at the water-sediment
      interface. This process occurs when long leaves, during poor nutrient periods in
      the water column, providing, to P. oceanica, the possibility to develop, high
      biomass, high chlorophyll quantities in low nutrient environment (a Low Nutrients
      High Chlorophyll system).

PMID- 12188925
TI  - Reduced natriuretic response to acute sodium loading in COMT gene deleted mice.
AB  - BACKGROUND: The intrarenal natriuretic hormone dopamine (DA) is metabolised by
      catechol-O-methyltransferase (COMT) and monoamine oxidase (MAO). Inhibition of
      COMT, as opposed to MAO, results in a potent natriuretic response in the rat. The
      present study in anaesthetized homozygous and heterozygous COMT gene deleted mice
      attempted to further elucidate the importance of COMT in renal DA and sodium
      handling. After acute intravenous isotonic sodium loading, renal function was
      followed. RESULTS: COMT activity in heterozygous mice was about half of that in
      wild type mice and was zero in the homozygous mice. MAO activity did not differ
      between the genotypes. Urinary sodium excretion increased 10-fold after sodium
      loading in wild type mice. In heterozygous and homozygous mice, the natriuretic
      effects of sodium loading were only 29 % and 39 %, respectively, of that in wild
      type mice. Arterial pressure and glomerular filtration rate did not differ
      between genotypes. Baseline norepinephrine and DA excretions in urine were
      elevated in the homozygous, but not in heterozygous, COMT gene deleted mice.
      Urinary DA excretion increased after isotonic sodium loading in the wild type
      mice but not in the COMT gene deleted mice. CONCLUSIONS: Mice with reduced or
      absent COMT activity have altered metabolism of catecholamines and are unable to
      increase renal DA activity and produce normal natriuresis in response to acute
      sodium loading. The results support the hypothesis that COMT has an important
      role in the DA-mediated regulation of renal sodium excretion.

PMID- 12188928
TI  - Chromosome 4q;10q translocations; comparison with different ethnic populations
      and FSHD patients.
AB  - BACKGROUND: Facioscapulohumeral muscular dystrophy (FSHD) is an autosomal
      dominant disorder characterized by the weakness of facial, shoulder-girdle and
      upper arm muscles. Most patients with FSHD have fewer numbers of tandem repeated
      3.3-kb KpnI units on chromosome 4q35. Chromosome 10q26 contains highly homologous
      KpnI repeats, and inter-chromosomal translocation has been reported. METHODS: To
      clarify the influence on the deletion of the repeats, we surveyed three different
      ethnic populations and FSHD patients using the BglII/BlnI dosage test. RESULTS:
      The frequency of translocation in 153 Japanese, 124 Korean, 114 Chinese healthy
      individuals and 56 Japanese 4q35-FSHD patients were 27.5%, 29.8%, 19.3%, and
      32.1%, respectively. The ratio of '4 on 10' (trisomy and quatrosomy of chromosome
      4) was higher than that of '10 on 4' (nullsomy and monosomy of chromosome 4) in
      all populations. CONCLUSIONS: The inter-chromosomal exchange was frequently
      observed in all four populations we examined, and no significant difference was
      observed between healthy and diseased groups.

PMID- 12188927
TI  - An examination of the Apo-1/Fas promoter Mva I polymorphism in Japanese patients
      with multiple sclerosis.
AB  - BACKGROUND: The Apo-1/Fas (CD95) molecule is an apoptosis-signaling cell surface
      receptor belonging to the tumor necrosis factor (TNF) receptor family. Both Fas
      and Fas ligand (FasL) are expressed in activated mature T cells, and prolonged
      cell activation induces susceptibility to Fas-mediated apoptosis. The Apo-1/Fas
      gene is located in a chromosomal region that shows linkage in multiple sclerosis
      (MS) genome screens, and studies indicate that there is aberrant expression of
      the Apo-1/Fas molecule in MS. METHODS: Mva I polymorphism on the Apo-1/Fas
      promoter gene was detected by PCR-RFLP from the DNA of 114 Japanese patients with
      conventional MS and 121 healthy controls. We investigated the association of the
      Mva I polymorphism in Japanese MS patients using a case-control association study
      design. RESULTS: We found no evidence that the polymorphism contributes to
      susceptibility to MS. Furthermore, there was no association between Apo-1/Fas
      gene polymorphisms and clinical course (relapsing-remitting course or secondary
      progressive course). No significant association was observed between Apo-1/Fas
      gene polymorphisms and the age at disease onset. CONCLUSIONS: Overall, our
      findings suggest that Apo-1/Fas promoter gene polymorphisms are not conclusively
      related to susceptibility to MS or the clinical characteristics of Japanese
      patients with MS.

PMID- 12188929
TI  - Dorsal horn-enriched genes identified by DNA microarray, in situ hybridization
      and immunohistochemistry.
AB  - BACKGROUND: Neurons in the dorsal spinal cord play important roles in nociception
      and pain. These neurons receive input from peripheral sensory neurons and then
      transmit the signals to the brain, as well as receive and integrate descending
      control signals from the brain. Many molecules important for pain transmission
      have been demonstrated to be localized to the dorsal horn of the spinal cord.
      Further understanding of the molecular interactions and signaling pathways in the
      dorsal horn neurons will require a better knowledge of the molecular neuroanatomy
      in the dorsal spinal cord. RESULTS: A large scale screening was conducted for
      genes with enriched expression in the dorsal spinal cord using DNA microarray and
      quantitative real-time PCR. In addition to genes known to be specifically
      expressed in the dorsal spinal cord, other neuropeptides, receptors, ion
      channels, and signaling molecules were also found enriched in the dorsal spinal
      cord. In situ hybridization and immunohistochemistry revealed the cellular
      expression of a subset of these genes. The regulation of a subset of the genes
      was also studied in the spinal nerve ligation (SNL) neuropathic pain model. In
      general, we found that the genes that are enriched in the dorsal spinal cord were
      not among those found to be up-regulated in the spinal nerve ligation model of
      neuropathic pain. This study also provides a level of validation of the use of
      DNA microarrays in conjunction with our novel analysis algorithm (SAFER) for the
      identification of differences in gene expression. CONCLUSION: This study
      identified molecules that are enriched in the dorsal horn of the spinal cord and
      provided a molecular neuroanatomy in the spinal cord, which will aid in the
      understanding of the molecular mechanisms important in nociception and pain.

PMID- 12188932
TI  - Clinical utility of measures of breathlessness.
AB  - BACKGROUND: The clinical utility of measures of dyspnea has been debated in the
      health care community. Although breathlessness can be evaluated with various
      instruments, the most effective dyspnea measurement tool for patients with
      chronic lung disease or for measuring treatment effectiveness remains uncertain.
      Understanding the evidence for the validity and reliability of these instruments
      may provide a basis for appropriate clinical application. OBJECTIVE: Evaluate
      instruments designed to measure breathlessness, either as single-symptom or
      multidimensional instruments, based on psychometrics foundations such as
      validity, reliability, and discriminative and evaluative properties.
      Classification of each dyspnea measurement instrument will recommend clinical
      application in terms of exercise, benchmarking patients, activities of daily
      living, patient outcomes, clinical trials, and responsiveness to treatment.
      METHODS: Eleven dyspnea measurement instruments were selected. Each instrument
      was assessed as discriminative or evaluative and then analyzed as to its
      psychometric properties and purpose of design. RESULTS: Descriptive data from all
      studies were described according to their primary patient application (ie,
      chronic obstructive pulmonary disease, asthma, or other patient populations). The
      Borg Scale and the Visual Analogue Scale are applicable to exertion and thus can
      be applied to any cardiopulmonary patient to determine dyspnea. All other
      measures were determined appropriate for chronic obstructive pulmonary disease,
      whereas the Shortness of Breath Questionnaire can be applied to cystic fibrosis
      and lung transplant patients. The most appropriate utility for all instruments
      was measuring the effects on activities of daily living and for benchmarking
      patient progress. Instruments that quantify function and health-related quality
      of life have great utility for documenting outcomes but may be limited as to
      documenting treatment responsiveness in terms of clinically important changes.
      CONCLUSIONS: The dyspnea measurement instruments we studied meet important
      standards of validity and reliability. Discriminative measures have limited
      clinical utility and, when used for populations or conditions for which they are
      not designed or validated, the data collected may not be clinically relevant.
      Evaluative measures have greater clinical utility and can be applied for outcome
      purposes. Measures should be applied to the populations and conditions for which
      they were designed. The relationship between clinical therapies and the
      measurement of dyspnea as an outcome can develop as respiratory therapists become
      more comfortable with implementing dyspnea measurement instruments and use the
      data to improve patient treatment. Dyspnea evaluation should be considered for
      all clinical practice guidelines and care pathways.

PMID- 12188930
TI  - In silico and in situ characterization of the zebrafish (Danio rerio) gnrh3
      (sGnRH) gene.
AB  - BACKGROUND: Gonadotropin releasing hormone (GnRH) is responsible for stimulation
      of gonadotropic hormone (GtH) in the hypothalamus-pituitary-gonadal axis (HPG).
      The regulatory mechanisms responsible for brain specificity make the promoter
      attractive for in silico analysis and reporter gene studies in zebrafish (Danio
      rerio). RESULTS: We have characterized a zebrafish [Trp7, Leu8] or salmon (s)
      GnRH variant, gnrh3. The gene includes a 1.6 Kb upstream regulatory region and
      displays the conserved structure of 4 exons and 3 introns, as seen in other
      species. An in silico defined enhancer at -976 in the zebrafish promoter,
      containing adjacent binding sites for Oct-1, CREB and Sp1, was predicted in 2
      mammalian and 5 teleost GnRH promoters. Reporter gene studies confirmed the
      importance of this enhancer for cell specific expression in zebrafish.
      Interestingly the promoter of human GnRH-I, known as mammalian GnRH (mGnRH), was
      shown capable of driving cell specific reporter gene expression in transgenic
      zebrafish. CONCLUSIONS: The characterized zebrafish Gnrh3 decapeptide exhibits
      complete homology to the Atlantic salmon (Salmo salar) GnRH-III variant. In
      silico analysis of mammalian and teleost GnRH promoters revealed a conserved
      enhancer possessing binding sites for Oct-1, CREB and Sp1. Transgenic and
      transient reporter gene expression in zebrafish larvae, confirmed the importance
      of the in silico defined zebrafish enhancer at -976. The capability of the human
      GnRH-I promoter of directing cell specific reporter gene expression in zebrafish
      supports orthology between GnRH-I and GnRH-III.

PMID- 12188933
TI  - Relationship of neonatal endotracheal tube size and airway resistance.
AB  - BACKGROUND: Infants receiving mechanical ventilation require narrow-lumen, small
      diameter endotracheal tubes. OBJECTIVE: Compare the resistances of endotracheal
      tubes used in the neonatal intensive care unit. METHODS: Endotracheal tubes of
      internal diameter 2.5, 3.0, 3.5, and 4.0 mm were tested with a standard neonatal
      ventilator and a test lung. An endotracheal tube of each diameter was cut to 12
      cm and connected to a flow transducer at one end and the test lung at the other.
      Serial measurements of resistance were made at various flows (6, 8, 10, and 12
      L/min) and ventilator rates (30-90 breaths/min) encompassing the ranges of
      clinical practice. Analysis of variance was performed for each tube size,
      comparing resistance to flows and ventilator rates. RESULTS: Resistance was
      significantly higher with the 2.5 mm tube than with the others. There was also a
      consistent trend, in all the tube sizes, towards higher resistance as flow was
      increased. CONCLUSIONS: The higher resistance of the 2.5 mm tube may be
      detrimental to extremely low birthweight infants kept on mechanical support
      merely "to grow." The higher resistance may increase the work of breathing and
      thus increase caloric expenditure and impede growth.

PMID- 12188931
TI  - The F-box protein SKP2 mediates androgen control of p27 stability in LNCaP human
      prostate cancer cells.
AB  - BACKGROUND: The cyclin-dependent kinase inhibitor p27 is a putative tumor
      suppressor that is downregulated in the majority of human prostate cancers. The
      mechanism of p27 down-regulation in prostate cancers in unknown, but presumably
      involves increased proteolysis mediated by the SCFSKP2 ubiquitin ligase complex.
      Here we used the human prostate cancer cell line LNCaP, which undergoes G1 cell
      cycle arrest in response to androgen, to examine the role of the SKP2 F-box
      protein in p27 regulation in prostate cancer. RESULTS: We show that androgen
      induced G1 cell cycle arrest of LNCaP cells coincides with inhibition of cyclin
      dependent kinase 2 activity and p27 accumulation caused by reduced p27
      ubiquitylation activity. At the same time, androgen decreased expression of SKP2,
      but did not affect other components of SCFSKP2. Adenovirus-mediated
      overexpression of SKP2 led to ectopic down-regulation of p27 in asynchronous
      cells. Furthermore, SKP2 overexpression was sufficient to overcome p27
      accumulation in androgen arrested cells by stimulating cellular p27
      ubiquitylation activity. This resulted in transient activation of CDK2 activity,
      but was insufficient to override the androgen-induced G1 block. CONCLUSIONS: Our
      studies suggest that SKP2 is a major determinant of p27 levels in human prostate
      cancer cells. Based on our in vitro studies, we suggest that overexpression of
      SKP2 may be one of the mechanisms that allow prostate cancer cells to escape
      growth control mediated by p27. Consequently, the SKP2 pathway may be a suitable
      target for novel prostate cancer therapies.

PMID- 12188934
TI  - Huge pulmonary arteriovenous fistula: diagnosis and treatment and an unusual
      complication of embolization.
AB  - We report the case of a 42-year-old woman with Rendu-Osler-Weber syndrome
      (hereditary hemorrhagic telangiectasia) and a huge pulmonary arteriovenous
      fistula that involved the entire right middle lobe. She had a history of dyspnea
      and intermittent atrial flutter for 6 months. A chest radiograph showed a
      discrete shadowing of the middle part of the right lung. Arteriovenous fistula
      was suspected based on the echocardiographic finding of immediate bubble
      detection in the left atrium on introducing echocardiographic contrast medium
      into the venous system. Atrial shunt was excluded. Angiography revealed a huge
      pulmonary arteriovenous fistula in the entire middle lobe of the right lung. A
      trial of interventional embolization was performed, but the size of the fistula
      made it impossible to achieve complete closure of all segmental fistulas.
      Furthermore, the patient complained of unusual, severe chest pain after
      implantation of the first coil, so that the coil had to be removed. Therefore the
      patient underwent surgical resection of the entire right middle lobe and the
      upper part of the right lower lobe. Anatomy was clearly delineated and all
      connecting vessels were suture-closed, but both lungs showed diffuse microscopic
      superficial pulmonary arteriovenous fistulas, which were too small to be detected
      by angiography and which were also partly closed. The postoperative course was
      uneventful: the patient recovered completely, she no longer had shortness of
      breath, and blood gas analysis showed normal P(aO)(2). It is not clear whether
      the patient's improved physical performance will last, because the development of
      diffuse microscopic arteriovenous fistulas bilaterally in the lungs is not
      predictable. Therefore close follow-up is necessary and in the case of recurrence
      (ie, enlargement of the existing small fistulas), early interventional
      embolization should be performed.

PMID- 12188935
TI  - Anticipatory use of venoarterial extracorporeal membrane oxygenation for a high
      risk interventional cardiac procedure.
AB  - Venoarterial extracorporeal membrane oxygenation (VA ECMO) has become a valuable
      technique in the critical care of children with congenital heart disease who
      require mechanical cardiorespiratory support. The use of VA ECMO in cardiac
      patients has expanded from an extension of intraoperative cardiopulmonary bypass
      and now includes rescue therapy during cardiopulmonary resuscitation, temporary
      circulatory support for reversible heart failure, and bridge support preceding
      heart or heart/lung transplantation. In the majority of clinical applications VA
      ECMO is used in reaction to impending or ongoing cardiorespiratory failure and
      not in anticipation of an induced change in clinical status. We describe the
      anticipatory use of VA ECMO to prepare a patient with complex cyanotic congenital
      heart disease for a high-risk interventional cardiac catheterization. A 2.5 kg
      neonate with severe Ebstein's anomaly of the tricuspid valve and recurrent
      episodes of life-threatening supraventricular tachycardia was electively
      cannulated for VA ECMO in the cardiac intensive care unit. She underwent
      successful electrophysiologic mapping and transcatheter radiofrequency ablation
      of an accessory conduction pathway, resulting in termination of the tachycardia.
      Following an uncomplicated ECMO course she was decannulated in the cardiac
      intensive care unit and subsequently discharged home in stable condition. The
      case illustrates the proactive use of ECMO during a procedure in which severe
      hemodynamic instability could be predicted. We discuss this concept of ECMO use
      in the context of accepted indications for ECMO in cardiac patients and encourage
      an expanded role for its use to prevent cardiorespiratory collapse in planned
      interventions on compromised patients who are at risk of acute deterioration.

PMID- 12188936
TI  - Mechanical ventilation strategies: what's new and what's worth keeping?
AB  - Many technologic and management strategies related to mechanical ventilation have
      been introduced in recent years. Strategies that avoid intubation and get
      patients extubated sooner decrease costs related to mechanical ventilation. In
      general, "people" solutions such as weaning protocols are preferable to
      "technology" solutions such as new ventilator modes. It must be remembered that
      mechanical ventilation is supportive-it is not curative-and has the potential to
      do harm if applied incorrectly. There is an increasing list of examples in which
      short-term physiologic outcomes such as improvements in blood gas values are not
      related to patient-important outcomes such as survival. When new mechanical
      ventilation technology and strategies are introduced, a question we need to ask
      ourselves is whether these are solutions for problems or whether these are simply
      solutions in search of problems.

PMID- 12188937
TI  - Effects of three-dimensional angiography on the coiling of cerebral aneurysms.
AB  - OBJECTIVE: To assess how information acquired with three-dimensional angiography
      (3DA) affects the endovascular management of cerebral aneurysms. METHODS: The
      role of 3DA in 50 aneurysm cases was assessed with respect to five predetermined
      factors, i.e., whether 3DA facilitated treatment, modified the coil embolization
      technique, made treatment unnecessary or unjustified by revealing new
      information, suggested a potential treatment failure or complication, or did not
      contribute to endovascular management. RESULTS: Findings for a total of 46
      patients with 50 aneurysms who underwent 3DA in the course of their endovascular
      treatment were analyzed. Overall, 3DA facilitated coiling in 25 cases, modified
      the treatment technique in 11 cases, eliminated the need for treatment in 9
      cases, and suggested a potential treatment complication in 5 cases. 3DA was
      deemed useful in the management of all cases, and in no case was its use
      associated with a complication. Specifically, 3DA facilitated treatment by
      delineating the optimal fluoroscopic tube angulation for coiling, modified
      treatment by revealing anatomic characteristics that would require balloon
      remodeling or stent assistance, obviated treatment by excluding the possibility
      of an aneurysm or by identifying unfavorable anatomic features, and predicted a
      treatment complication by revealing an associated vessel that was likely to be
      compromised with coiling of the aneurysm. CONCLUSION: 3DA enhances our ability to
      treat aneurysms endovascularly. Most importantly, aneurysm treatment may be
      facilitated, modified, or proven unnecessary because of vital information
      obtained with 3DA.

PMID- 12188938
TI  - Intracranial aneurysm surgery in Ehlers-Danlos syndrome Type IV.
AB  - OBJECTIVE: Ehlers-Danlos syndrome Type IV is a heritable connective tissue
      disorder with frequent neurovascular manifestations, such as intracranial
      aneurysms. Patients with this syndrome have notoriously fragile blood vessels,
      and the reported mortality rate for any type of vascular surgical procedure is
      40%. This syndrome is rare, however, and the complication rate of aneurysm
      surgery may have been overestimated. METHODS: We reviewed our experience with
      aneurysm surgery in a group of patients with Ehlers-Danlos syndrome Type IV.
      RESULTS: The patient population consisted of three women and one man with a mean
      age of 44 years (age range, 20-57 yr). One patient, who had a ruptured anterior
      circulation aneurysm, died as a direct result of surgery because of marked
      vascular fragility. Three patients underwent successful surgery, consisting of a
      craniotomy and clipping of a ruptured anterior circulation aneurysm in two
      patients and a craniotomy and clip ligation of the parent artery in one patient
      with a ruptured dissecting vertebral artery aneurysm. Intraoperatively, mild
      vascular or connective tissue fragility was commonly observed. Postoperative
      complications (e.g., spontaneous pneumothorax and vertebral artery dissection)
      also were common but did not result in permanent morbidity. CONCLUSION: The risk
      of neurovascular surgery is high in patients with Ehlers-Danlos syndrome Type IV
      and intra- and postoperative complications are common. However, most patients
      tolerate the operation without permanent morbidity.

PMID- 12188939
TI  - Magnetic source imaging demonstrates altered cortical distribution of function in
      patients with arteriovenous malformations.
AB  - OBJECTIVE: Arteriovenous malformations (AVMs) can be treated successfully, but
      treatment can pose unacceptable risks if the AVM is located in eloquent cortex.
      Because AVMs are developmental lesions, the location of primary cortical function
      may be deranged. We used magnetic source imaging (MSI) to identify the central
      sulcus and to determine whether primary cortical function was shifted in a set of
      30 patients. We correlated these findings with outcome after treatment. METHODS:
      We retrospectively analyzed the clinical data of 30 patients with AVMs who
      underwent MSI. Nonparametric statistical comparisons were made to correlate the
      proximity of AVMs to primary cortex and somatosensory shift to outcome at 12
      months. RESULTS: Using MSI, 14 patients (47%) were found to have AVMs involving
      primary cortex, and 10 patients (33%) were found to have shift in the
      somatosensory homunculus. Primary cortical involvement was neither required nor
      sufficient to cause shift (Mann-Whitney U test, z = -0.02, P = 0.31). Patients
      with AVMs involving primary cortex fared worse after treatment than did patients
      with AVMs that spared primary cortex (Mann-Whitney U test, z = -2.3, P = 0.02).
      The presence or absence of shift did not correlate with outcome after treatment
      (Mann-Whitney U test, z = -0.18, P = 0.48). CONCLUSION: MSI showed that some
      patients with AVMs have abnormal cortical distribution of function. The
      involvement of primary cortex correlated with worse outcome after treatment. Our
      results suggest that preoperative functional imaging may help to better estimate
      treatment risks and ultimately to guide therapeutic planning.

PMID- 12188940
TI  - Major clinical and physiological benefits of early high doses of mannitol for
      intraparenchymal temporal lobe hemorrhages with abnormal pupillary widening: a
      randomized trial.
AB  - OBJECTIVE: We evaluated long-term clinical outcomes and postoperative
      physiological findings in acutely comatose patients with nonmissile surgical
      intraparenchymal temporal lobe hemorrhages and abnormal pupillary widening who
      received early preoperative high-dose mannitol (HDM) versus conventional dose
      mannitol treatment in the emergency room. METHODS: One hundred forty-one adult
      patients with traumatic, nonmissile, acute, intraparenchymal temporal lobe
      hemorrhages associated with early abnormal pupillary widening were prospectively
      and randomly assigned to receive emergency preoperative intravenous HDM treatment
      (approximately 1.4 g/kg; 72 patients) and were compared with a control group that
      was treated with a lower preoperative mannitol dose (approximately 0.7 g/kg; 69
      patients). RESULTS: Early preoperative improvement of abnormal bilateral
      pupillary widening was significantly more frequent in the study group than in the
      control group (P < 0.03). The same was true for abnormal unilateral pupillary
      widening (P < 0.01). Early HDM treatment in the emergency room was also
      associated with significantly better 6-month clinical outcomes (P < 0.005). The
      two groups of patients were well matched with respect to diameter of the temporal
      lobe hemorrhages (approximately 4 cm) as well as timing of clot removal
      (approximately 2.5 hours after injury). Postoperative physiological findings
      revealed statistically significant between-group differences, with higher
      intracranial pressure and lower cerebral extraction of oxygen (global relative
      cerebral hyperperfusion) in the control group than in the HDM group.
      Postoperative global brain ischemia (abnormally low arteriojugular lactate
      difference values) was rare and was found for less than 3% of the patients in
      both groups. CONCLUSION: Early preoperative HDM administration in the emergency
      room was associated with improved clinical outcomes for adult comatose patients
      with acute, nonmissile, intraparenchymal temporal lobe hemorrhages and associated
      abnormal pupillary widening. Early improvement of bilateral or unilateral
      pupillary abnormalities and better postoperative control of intracranial
      hypertension and associated global relative cerebral hyperperfusion seemed to be
      relevant factors that were related to improved outcomes.

PMID- 12188941
TI  - Follow-up of stented carotid arteries by Doppler ultrasound.
AB  - OBJECTIVE: Blood flow velocity (BFV) in the carotid artery is altered by stent
      placement. The significance of these alterations is unknown. In our experience,
      both standard BFV criteria for stenosis and customized criteria recommended by
      other authors have led to high rates of false-positive studies. We reviewed our
      experience with Doppler ultrasonography immediately after extracranial carotid
      artery stent placement to define criteria for restenosis by BFV. METHODS:
      Complete carotid angiograms and BFV results were available for 114 patients
      treated between January 1998 and December 1999. Angiographic images obtained
      immediately after stent placement and at follow-up were measured for residual or
      recurrent stenosis by a blinded reviewer according to the North American
      Symptomatic Carotid Endarterectomy Trial method. Results of BFV studies obtained
      within 1 week of stent placement were interpreted by using two standard criteria
      (A, peak in-stent systolic velocity greater than 125 cm/s; B, internal carotid
      artery-to-common carotid artery ratio greater than 3.0) and two customized
      criteria (C, peak in-stent velocity greater than 170 cm/s; D, internal carotid
      artery-to-common carotid artery ratio greater than 2.0). The results of follow-up
      angiography and the most recent Doppler study were compared for nine patients.
      RESULTS: On the basis of an examination of Doppler studies obtained immediately
      after stent placement, 36 patients met Criterion A for stenosis according to
      measured BFV (corresponding mean angiographic stenosis, 14.73 +/- 18.45%), 3
      patients met Criterion B (mean stenosis, 1.67 +/- 2.89%), 8 patients met
      Criterion C (mean stenosis, 12.61 +/- 13.18%), and 14 met Criterion D (mean
      stenosis, 7.98 +/- 21.74%). No patient with Doppler criteria for significant
      stenosis had more than 50% residual stenosis. Three of nine patients who
      underwent follow-up angiography had stenosis of 50% or more; of these three
      patients, two underwent second angioplasty procedures. The peak in-stent systolic
      velocity or internal carotid artery-to-common carotid artery BFV ratio for each
      of the three patients with restenosis, but not for the six other patients, had
      increased by more than 80% since the immediate post-stenting Doppler study.
      CONCLUSION: Strict BFV criteria for restenosis after carotid artery stenting are
      less reliable than change in BFV over time. An immediate post-stenting Doppler
      study must be obtained to serve as a reference value for future follow-up
      evaluation.

PMID- 12188942
TI  - Surgery to treat focal frontal lobe epilepsy in adults.
AB  - OBJECTIVE: To report clinical, neuropathological, and outcome data for a series
      of adult patients with focal frontal lobe epilepsy (fFLE) who underwent nonlobar
      resection restricted to the frontal lobe. METHODS: Sixty-eight adult cases (24
      female and 44 male patients) were included in the study, on the basis of
      prospectively collected data that were retrospectively evaluated. There were 68
      lesionectomies, 17 of which were combined with multiple subpial transection, with
      a mean follow-up period of 28.4 +/- 23.3 months. Cases involving additional
      extrafrontal surgery were excluded. RESULTS: Thirty-seven patients underwent
      invasive preoperative evaluations, and 31 underwent noninvasive evaluations.
      Intraoperative electrocorticography was used in 32% of cases. There were 24
      tumors, 18 dysgenetic lesions, 14 gliotic lesions, and 10 vascular malformations.
      Fifteen tumors were of glial origin, one was a dysembryoplastic neuroepithelial
      tumor, and eight were gangliogliomas. The most common dysgenetic lesions were
      hamartomas (15 cases). Outcomes (classified into four Engel groups) were as
      follows: Class I, 54%; Class II, 19%; Class III, 15%; Class IV, 12%. Seizure-free
      rates were comparable for tumor and dysgenesis cases and were not as good for
      vascular malformation and gliosis cases. Outcome differences were not significant
      with respect to aura presence, side of surgery, age at the time of surgery, and
      age at seizure onset. There were 3 cases of surgical complications, 10 cases of
      transient neurological disturbances, and 1 case involving a permanent
      neurological deficit. No deaths occurred. CONCLUSION: Outcomes with fFLE surgery
      have improved, compared with historical series. fFLE resections restricted to the
      frontal lobe did not yield seizure-free rates as good as those for comparable
      nonfocal frontal lobe epilepsy series. All fFLE cases demonstrated histological
      lesions. fFLE surgery was associated with a higher risk of transient neurological
      deficits, most likely because of the necessity for multiple subpial transection.
      The outcomes and higher rates of invasive evaluations and intraoperative
      electrocorticography indicate the special complexities of frontal lobe epilepsy.
      The permanent neurological disability rate was low in this series, and there were
      no deaths.

PMID- 12188943
TI  - Stereotactic radiosurgery for patients with "radioresistant" brain metastases.
AB  - OBJECTIVE: Our aim was to evaluate the efficacy of stereotactic radiosurgery
      (SRS) for the treatment of patients with brain metastases that have been
      determined to be "radioresistant" on the basis of histological examination.
      METHODS: We reviewed the medical records of 41 consecutive patients who presented
      with 83 brain metastases from radioresistant primaries and subsequently underwent
      SRS. All patients were followed until death or for a median of 31 months after
      SRS. Tumor histologies included renal cell carcinoma (16 patients), melanoma (23
      patients), and sarcoma (2 patients). Eighteen patients (44%) had a solitary
      metastasis, and 23 patients (56%) had multiple metastases. RESULTS: The median
      overall survival time was 14.2 months after SRS. On the basis of univariate
      analysis, systemic disease status (P = 0.006) and Radiation Therapy Oncology
      Group recursive partitioning analysis (RPA) class (P = 0.005) were associated
      with survival. The median survival time was 23.5 months for patients in RPA Class
      I status and 10.5 months for patients in RPA Class II or III status. There was a
      trend (P = 0.12) toward improved median survival for patients with renal cell
      carcinoma (17.8 mo) as compared with patients with melanoma (9.7 mo).
      Multivariate analysis showed RPA class (P = 0.038) and histological diagnosis of
      primary tumor (P < 0.001) to be independent predictors for overall survival. In
      the 35 patients who underwent follow-up imaging, 9 (12%) of 73 tumors recurred
      locally. In 54% of the patients, distant brain failure (DBF) developed. Whole
      brain radiotherapy (WBRT) improved local control and decreased DBF, according to
      the univariate and multivariate analyses. Patients who received adjuvant WBRT in
      addition to SRS had 6-month actuarial local control of 100% as compared with 85%
      among those who did not receive WBRT (P = 0.018). Patients who received adjuvant
      WBRT with SRS had a 6-month actuarial DBF rate of 17%, as compared with a rate of
      64% among patients who had SRS alone (P = 0.0027). CONCLUSION: Well-selected
      patients with brain metastases from radioresistant primary tumors who undergo SRS
      survive longer than historical controls. RPA Class I status and primary renal
      cell carcinoma predict longer survival. Adjuvant WBRT improves local control and
      decreases DBF but does not affect overall survival. Further studies are needed to
      determine which patients should receive WBRT.

PMID- 12188944
TI  - Surgical treatment of nocardial brain abscesses.
AB  - OBJECTIVE: Nocardial brain abscesses are associated with significant morbidity
      and mortality rates. The optimal management remains unclear. We reviewed the
      surgical outcomes of patients treated with a relatively uniform policy at a
      single institution. METHODS: Eleven patients were treated at the Royal Adelaide
      Hospital between 1970 and 2001. Their clinical presentations, surgical treatment,
      and outcomes were reviewed. RESULTS: Clinical presentations most frequently
      involved focal neurological deficits (91%). Predisposing factors were identified
      for 63% of the patients. Nine patients were treated only with aspiration and long
      term chemotherapy. Two patients underwent craniotomy and lesion excision. The
      majority of patients required either one or two procedures. There were no deaths
      in this series. Management complications were observed for three patients.
      Abscess aspiration was complicated by parenchymal hemorrhage and ventriculitis
      for one patient and temporary worsening of hemiparesis for two patients.
      CONCLUSION: Our results suggest that aspiration alone (repeated as clinically
      indicated) is a safe, efficacious treatment for the majority of patients with
      nocardial brain abscesses.

PMID- 12188945
TI  - Brachial plexus injury: a survey of 100 consecutive cases from a single service.
AB  - OBJECTIVE: We analyzed the epidemiology, preoperative management, operative
      findings, operative treatment, and postoperative results in a group of 99
      patients who sustained 100 injuries to the brachial plexus. METHODS: The charts
      of 100 consecutive surgical patients with brachial plexus injuries were reviewed.
      RESULTS: The patient group comprised 80 males and 19 females ranging from 5 to 70
      years of age. One male patient had bilateral brachial plexus palsy. Causes of
      injury were largely sudden displacement of head, neck, and shoulder and included
      27 motorcycle accidents. There were 23 open wounds, including 8 gunshot wounds, 6
      other penetrating wounds, and 9 wounds caused by operative or iatrogenic trauma.
      Loss was exhibited at C5-C6 in 19 patients, at C5-C7 in 15 patients, and at C5-T1
      in 39 patients, and 8 patients had another spinal root pattern of injury.
      Nineteen patients had injury at the cord or the cord to nerve level. Associated
      major trauma was present in 59 patients. Emergency surgery for vessel or nerve
      repair was necessary in 18 patients. Myelography (n = 57) or magnetic resonance
      imaging (n = 7) revealed at least one root abnormality in 52 patients. The median
      interval from trauma to operation was 7 months. Operative exposures used included
      anterior supraclavicular, infraclavicular, combined supra- and infraclavicular,
      or a posterior approach in 5, 14, 77, and 4 patients, respectively. The surgical
      procedures performed included neurolysis alone in 12 patients and nerve grafting,
      end-to-end anastomosis, and/or neurotization in 81, 5, and 47 patients,
      respectively. Postoperative follow-up of at least 36 months was conducted in 78%
      of the patients. Grade 3 recovery according to Louisiana State University Medical
      Center criteria means contraction of proximal muscles against some resistance and
      of distal muscles against at least gravity. Among the 18 patients with open
      wounds, 14 (78%) recovered to a Grade 3 or better level, as did 35 (58%) of 60
      patients with stretch injuries. In all cases of C5-C6 stretch injuries repaired
      by nerve grafting (n = 10), the patients recovered useful arm function.
      CONCLUSION: Brachial plexus injury represents a severe, difficult-to-handle
      traumatic event. The incidence of such injuries and the indications for surgery
      have increased during recent years. Graft repair and neurotization procedures
      play an important role in the treatment of patients with such injuries.

PMID- 12188946
TI  - Treatment of relevant nerve roots involved in nerve sheath tumors: removal or
      preservation?
AB  - OBJECTIVE: Surgery for the treatment of patients with spinal nerve sheath tumors
      can require complete resection of the nerve roots involved in the tumor. The
      purpose of the present study is to analyze the risks of resection of eloquent
      roots as compared with the risks of incomplete tumor removal. METHODS: The
      pertinent literature on spinal nerve sheath tumors was reviewed. A single
      institution series of 26 patients who underwent operations for 27 spinal
      schwannomas or neurofibromas, which were removed together with functionally
      relevant nerve roots (C5-C8 or L3-S1), was studied. RESULTS: Worsening of
      preoperative radicular motor function was observed at follow-up in 4 (14.8%) of
      the 27 divided nerve roots, but the motor deficit was permanent and disabling in
      only 2 cases (7.4%). In the four patients who experienced worsened radicular
      motor function, the roots were cervical, and histological analysis revealed that
      the tumor was a schwannoma. Three of these patients were neurologically negative
      before surgery. Of the two patients with severe radicular weakness, the location
      of the tumor was extradural and extraradicular in one patient, who had normal
      preoperative root function, and the tumor was intraextradural in the other
      patient, who had a preoperative root deficit. CONCLUSION: After resection of a
      single eloquent nerve root involved in a nerve sheath tumor, the incidence of
      radicular dysfunction is low but severe weakness is possible. The main risk
      factors seem to be the pathological pattern (schwannoma versus neurofibroma) of
      tumor, the preoperative status (with versus without deficit) of the root, and,
      for extradural nerve sheath tumors, the location (cervical and extraradicular
      versus lumbosacral and intraradicular) of growth. Deafferentation pain does not
      occur. Unlike schwannomas with neurofibromatosis Type 2 and neurofibromas, the
      radicality of removal seems to be the main factor with regard to the recurrence
      of solitary schwannomas, although recurrent tumors often appear later in follow
      up.

PMID- 12188947
TI  - Coiling of cerebral aneurysm remnants after clipping.
AB  - OBJECTIVE: During the past decade, options for the management of aneurysm
      remnants after clipping have expanded. Advances in aneurysm coiling techniques
      and technology have allowed for more remnants to be treated safely. We present
      our experience with this approach and discuss its indications, limitations, and
      results. METHODS: We retrospectively reviewed the Northwestern Memorial Hospital
      experience with aneurysm coiling between January 1996 and June 2001. We
      identified five patients who underwent coiling for aneurysm remnants after
      clipping. We reviewed the clinical history, all follow-up notes, and all relevant
      imaging studies. We also reviewed MEDLINE for all articles published in the
      English language between 1990 and September 2001 that included patients treated
      with this approach. RESULTS: Complete to near-complete aneurysm occlusion was
      achieved in all five patients in our study. There was no permanent morbidity or
      mortality associated with the procedure in any of these patients. In the
      literature, we found seven articles that discuss 21 patients who were treated
      with coiling for their remnants. There were no permanent complications reported
      for these 21 patients. Adequate long-term follow-up in these 21 patients,
      however, is lacking. CONCLUSION: Complete aneurysm occlusion is the goal of
      aneurysm clipping. When this goal cannot be achieved safely, coiling of the
      remnant, if size and morphology are amenable, is a safe option that should be
      considered. Clinical and angiographic long-term follow-up of patients treated in
      this manner should be studied and reported.

PMID- 12188948
TI  - Endoscopic transsphenoidal approach: adaptability of the procedure to different
      sellar lesions.
AB  - OBJECTIVE: To demonstrate the flexibility of the endoscopic transsphenoidal
      approach, with respect to nasal and paranasal anatomic features and the extension
      of different sellar lesions, for customization of the procedure for specific
      conditions. METHODS: In 16 of 170 consecutive endoscopic transsphenoidal
      operations, some modifications of the standard approach were adopted to optimize
      surgical removal of different lesions. These modifications consisted of a
      hemisphenoidotomy, a partial ethmoidectomy, extended sellar floor opening toward
      the planum sphenoidale or the clivus, enlarged opening of the sphenoid ostium
      area with ipsilateral removal of the superior turbinate, and a bilateral
      approach. RESULTS: The endoscopic endonasal procedure is easily adaptable to
      different specific conditions, with slight changes in the standard approach (more
      or less invasive). Therefore, this surgical procedure is satisfactory for
      different lesion locations and for the nasal and paranasal sinus anatomic
      features of individual patients. CONCLUSION: The endoscopic surgical route should
      be tailored to different sellar lesions, and some modifications of the procedure
      are recommended in selected cases.

PMID- 12188949
TI  - Combined petrosal approach to petroclival meningiomas.
AB  - OBJECTIVE: To study the use and advantages of combining the posterior petrosal
      approach with the anterior petrosal approach to petroclival meningiomas. METHODS:
      Seven cases of petroclival meningiomas operated on via the combined petrosal
      approach were retrospectively analyzed. The basis on which this approach was
      selected was assessed, as were its benefits and risks. RESULTS: Gross total
      resection was achieved in five of the seven patients. No mortality or decrease in
      Karnofsky performance score was observed at the time of the last follow-up
      examination. Six of the seven patients had serviceable hearing before the
      operation. Only one patient lost hearing after the operation, and this hearing
      loss occurred in only one ear. Before the operation, six patients were House
      Brackmann facial nerve function Grade I, and one patient was Grade II to III. At
      the last follow-up examination, facial nerve function was Grade I in five
      patients, Grade II in one patient, and Grade V in one patient. Tumors in all
      patients involved the cavernous sinus, Meckel's cave, petroclival junction, and
      middle clivus. All patients possessed a large posterior fossa component of tumor
      measuring an average of 3.6 x 3.5 x 4.2 cm. In four patients, the tumor was
      attached for the entire width of the clivus to the contralateral petroclival
      junction. Four patients displayed central brainstem compression. Four patients
      displayed bony changes at the petrous apex. All patients displayed total or
      partial encasement of the vertebrobasilar artery and its major branches.
      CONCLUSION: The combined petrosal approach should be considered for patients who
      have a large petroclival meningioma and serviceable hearing. This approach
      enhances petroclival exposure and the degree of tumor resection, especially in
      the area of the petroclival junction, middle clivus, apical petrous bone,
      posterior cavernous sinus, and Meckel's cave. The combined petrosal approach also
      allows better visualization of the contralateral side and the ventral brainstem,
      which facilitates safe dissection of the tumor from the brainstem, the basilar
      artery, and the perforators. If a patient has an early draining bridging vein to
      the tentorial sinus (before it reaches the transverse-sigmoid junction) or a
      prominent sigmoid sinus and jugular bulb, the combined petrosal approach provides
      significant working space.

PMID- 12188950
TI  - Operative nuances of myelomeningocele closure.
AB  - ALTHOUGH ADVANCES IN prenatal care and diagnosis have reduced the incidence of
      spina bifida, repair of neural tube defects remains one of the standard cases
      encountered by pediatric neurosurgeons. The operative techniques used in closure
      of these congenital defects have remained essentially unchanged during the past 2
      decades; however, the operative nuances for closure often are based on the
      variability in configuration and size of the open defects, which can present a
      challenge. Repair of the open spinal dysraphism may require only a simple
      closure, but extensive dissection and reconstruction of the neural, meningeal,
      fascial, and epidermal tissues, including the use of specialized vascularized
      flaps, may be required in some cases. In this article, we briefly describe the
      preoperative evaluation, decision process, and standard techniques for the repair
      of myelomeningocele and myeloschisis.

PMID- 12188951
TI  - Anatomic study of the filum terminale and its correlations with the tethered cord
      syndrome.
AB  - OBJECTIVE: To evaluate the intradural anatomic features of the filum terminale
      (FT) in fresh human cadavers, analyzing morphological parameters relevant for the
      diagnosis of the tethered cord syndrome. METHODS: Forty-one fresh cadavers were
      dissected, and the following parameters were evaluated: cadaver height, weight,
      and age, FT length, FT diameters at the initial point and midpoint, and
      topographic relationships of the initial and fusion points of the FT to the
      adjacent vertebrae. RESULTS: The mean FT length was 156.44 mm (range, 112.8-211.1
      mm), the mean initial diameter was 1.38 mm (range, 0.4-2.5 mm), and the mean
      midpoint diameter was 0.76 mm (range, 0.1-1.55 mm). Four specimens (9.76%)
      exhibited FT thicknesses of more than 2 mm at their initial points. The FT most
      frequently started at the middle L1 level (19.51%) and fused with the dura mater
      at the upper S2 level (31.71%). Two fila (4.88%) started below the L2 level.
      Statistically significant correlations were observed (Pearson correlation, P <
      0.05) between specimen weight and height (P = 0.019), initial point and midpoint
      diameters of the FT (P < 0.001), initial vertebral level and specimen height (P =
      0.012), and initial and fusion vertebral levels (P = 0.004). CONCLUSION:
      Variation ranges were large for almost all anatomic parameters of the FT. Six
      cadavers (14.63%) in our study fulfilled one of the anatomic diagnostic criteria
      for tethered cord syndrome. Neurosurgeons must remember the normal variations in
      the anatomic features of this region when establishing the diagnosis of tethered
      cord syndrome or performing surgical procedures involving the caudal part of the
      dural sac.

PMID- 12188952
TI  - Brain death documentation: analysis and issues.
AB  - OBJECTIVE: Specific guidelines for documenting the complete loss of brain
      function, for the declaration of brain death, have been established for 3
      decades. This study assessed the quality and completeness of brain death notes
      and the effects of delays between notes on organ procurement. METHODS: A
      retrospective review of brain death declarations at a major medical center was
      performed. Fifty-eight cases, with a total of 121 brain death notes, were
      identified in a 12-month period. Notes were assessed for clinical and
      confirmatory tests of brain and brainstem function. Adverse physiological events
      that occurred in the time intervals between notes were also identified. RESULTS:
      The clinical tests most likely to be documented were tests of pupillary (86%) and
      gag (78%) reflexes. Corneal reflexes were tested in only 57% of cases, and motor
      responses were noted in only 66%. Documentation by the neurosurgery department
      was generally more complete. The delays between brain death declarations were
      highly variable but did not result in any loss of donor organs because of
      hemodynamic derangements. CONCLUSION: To meet the needs of organ recipients and
      donor families and to comply with hospital, legal, and legislative mandates,
      hospitals may need to increase quality assurance activities with respect to
      declarations of brain death. Increased physician education should improve
      awareness of uniform brain death declaration guidelines.

PMID- 12188953
TI  - The origin of "Saturday night palsy"?
AB  - THE TERM Saturday night palsy has become synonymous with radial nerve compression
      in the arm resulting from direct pressure against a firm object. It typically
      follows deep sleep on the arm, often after alcohol intoxication. The commonly
      accepted origin of the phrase is the association of Saturday night with
      carousing. We offer an alternate explanation: we think that the term Saturday
      night palsy was introduced mistakenly as a simplification of saturnine palsy
      (much like the way the word palsy was shortened from paralysis). Saturnine palsy,
      which is a relatively common complication of lead poisoning, has the same
      clinical presentation of radial nerve compression, and Saturday night palsy even
      sounds like saturnine palsy. Moreover, Saturday, lead, carousing, and alcohol are
      associated with each other through their connection to Saturn, the Roman god of
      agriculture, which encourages the association of the two syndromes with one
      another.

PMID- 12188954
TI  - Biodegradable polymer grafts for surgical repair of the injured spinal cord.
AB  - PURPOSE: Biodegradable polymers have been used in the surgical repair of
      peripheral nerves, but their potential for use in the central nervous system has
      not been exploited adequately. This article discusses concepts related to the
      engineering of a biodegradable polymer graft for surgical repair of the injured
      spinal cord and explores the potential means by which such a device might promote
      axon regeneration and functional recovery after spinal cord injury. CONCEPT: A
      biodegradable polymer implant with controlled microarchitecture can be
      engineered, and its composition can be optimized for implantation in the spinal
      cord. RATIONALE: The use of a biodegradable polymer implant has the dual
      advantages of providing a structural scaffold for axon growth and a conduit for
      sustained-release delivery of therapeutic agents. As a scaffold, the
      microarchitecture of the implant can be engineered for optimal axon growth and
      transplantation of permissive cell types. As a conduit for the delivery of
      therapeutic agents that may promote axon regeneration, the biodegradable polymer
      offers an elegant solution to the problems of local delivery and controlled
      release over time. Thus, a biodegradable polymer graft would theoretically
      provide an optimal structural, cellular, and molecular framework for the regrowth
      of axons across a spinal cord lesion and, ultimately, neurological recovery.
      CONCLUSION: Biodegradable polymer grafts may have significant therapeutic
      potential in the surgical repair of the injured spinal cord. Further research
      should be focused on the bioengineering, characterization, and experimental
      application of these devices.

PMID- 12188955
TI  - Expression of growth factors and structural proteins in chordomas: basic
      fibroblast growth factor, transforming growth factor alpha, and fibronectin are
      correlated with recurrence.
AB  - OBJECTIVE: To test the hypothesis that the expression of certain growth factors
      and/or structural proteins is correlated with the biological behavior of cranial
      base chordomas. METHODS: The study investigated 14 pathological specimens of
      cranial base chordomas from patients who were monitored for at least 2 years
      after their initial operations. Some cases involved multiple tumor recurrences
      and multiple operations. For those patients, the time to recurrence after each
      operation was recorded and a mean value was calculated. Nine patients with mean
      times to recurrence of 24 months or more or with 24 months of follow-up
      monitoring without recurrence after single operations were designated the "good
      prognosis" group. Five patients with mean times to recurrence of less than 24
      months were designated the "poor-prognosis" group. In each case, only the
      specimen from the initial operation was studied. Multiple sequential sections
      were cut from paraffin-embedded blocks of tissue and immunohistochemically
      prepared for detection of three growth factors and three structural proteins,
      i.e., basic fibroblast growth factor, transforming growth factor alpha, vascular
      endothelial growth factor, fibronectin, collagen III, and collagen IV. Intensity
      of expression was graded by using a four-tier system (Grades 0, 1, 2, and 3).
      Levels of expression of the molecules in the two groups were evaluated and
      compared. RESULTS: The mean transforming growth factor alpha expression intensity
      grades for the good- and poor-prognosis groups were 0.8 and 2.6, respectively,
      and the corresponding mean basic fibroblast growth factor grades were 1.4 and
      2.6. For both groups, the mean grade for vascular endothelial growth factor
      expression was 0.6. For fibronectin, the mean staining grades for the good- and
      poor-prognosis groups were 2.2 and 3.0, respectively. The corresponding mean
      intensities for collagen III were 1.1 and 0.8, and those for collagen IV were 2.5
      and 2.6. CONCLUSION: Our descriptive data from immunohistochemical analyses of
      chordomas suggest that high levels of transforming growth factor alpha and basic
      fibroblast growth factor expression are linked to higher rates of recurrence.
      Strong fibronectin expression may also be a marker of aggressive biological
      behavior.

PMID- 12188957
TI  - Norepinephrine in the rat cortex before and after occlusion of chronic
      arteriovenous fistulae: a microdialysis study in an animal model of cerebral
      arteriovenous malformations.
AB  - OBJECTIVE: In an animal model, we tested the hypothesis that intracerebral,
      extracellular norepinephrine (NE) influences cerebral blood flow (CBF) in the
      presence of cerebral arteriovenous malformations (AVMs). METHODS: A microdialysis
      (MD) probe was implanted into the cortices of Sprague-Dawley rats 3 months after
      the creation of extracranial arteriovenous fistulae (AVFs; n = 19), carotid
      ligation (n = 10), and cervical vessel preparation (sham operations; n = 8).
      Ipsilateral regional cortical oxygen saturation (microspectrophotometry) and
      regional cerebral blood flow (laser Doppler flowmetry) were scanned with
      simultaneous MD sampling for NE (high-performance liquid chromatography). Local
      CBF and cortical capillary oxygen saturation (SO2) were recorded continuously
      with serial MD sampling after fistula occlusion for 100 minutes. The scanning
      protocol was repeated after 120 minutes. Values were compared by analysis of
      variance and Duncan's test (P < 0.05; values expressed as mean +/- standard
      deviation). RESULTS: NE was highest in sham-operated animals and lowest after
      carotid ligation as compared with before and after the creation of the AVFs (sham
      operations, 5.9 +/- 2.3 nmol/L; common carotid artery ligation, 2.4 +/- 1 nmol/L;
      before creation of AVF, 4.1 +/- 1.9 nmol/L; after creation of AVF, 4.1 +/- 2.3
      nmol/L). Regional cortical oxygen saturation differed significantly between all
      groups; regional cerebral blood flow was lower only in sham-operated animals
      (sham operations, 210 +/- 75 laser Doppler units [LDU], 71 +/- 13% SO2; common
      carotid artery ligation, 250 +/- 82 LDU, 62 +/- 19% SO2; before creation of AVF,
      249 +/- 96 LDU, 65 +/- 14% SO2; after creation of AVF, 256 +/- 82 LDU, 74 +/- 10%
      SO2). After fistula occlusion, a sustained CBF increase for 100 minutes up to 40%
      above baseline (i.e., regional cerebral blood flow and regional cortical oxygen
      saturation before occlusion) was observed. SO2 increased to 16% after 120
      minutes. Peaks of NE concentrations occurred 40 minutes and 100 minutes after
      fistula occlusion. CONCLUSION: The model seems to be valid for the simulation of
      events that occur before and after the obliteration of human cerebral AVMs in
      most cases, but not in those prone to hyperperfusion syndromes. The results
      provide evidence that cerebral sympathetic nervous system activity can be
      monitored by in vivo MD and that NE may play a role in CBF control before and
      after the obliteration of AVFs.

PMID- 12188956
TI  - Intracisternal sodium nitroprusside fails to prevent vasospasm in nonhuman
      primates.
AB  - OBJECTIVE: Hemoglobin contributes to vasospasm after subarachnoid hemorrhage. One
      mechanism may involve binding of nitric oxide, destruction of nitric oxide, or
      both. Support for this mechanism would be evidence that nitric oxide donors
      prevent vasospasm. This study attempted to provide such evidence. METHODS: A
      randomized, blinded study was conducted in which 13 monkeys underwent cerebral
      angiography and creation of a right subarachnoid hemorrhage. Subcutaneous osmotic
      pumps were implanted to deliver sodium nitroprusside (n = 7) or vehicle (n = 6)
      via catheters into the right basal cisterns. Seven days later, angiography was
      repeated, and the animals were humanely killed. Levels of cyclic nucleotides,
      hemoglobins, and thiocyanate were measured. RESULTS: Significant vasospasm of the
      right middle cerebral artery was present in animals treated with sodium
      nitroprusside (35 +/- 22% reduction in diameter, P < 0.05, paired t test) and
      placebo (28 +/- 20% reduction, P < 0.05, not significantly different from
      nitroprusside group by unpaired t test). Adequate delivery of sodium
      nitroprusside was supported by the finding of a significant increase in cyclic
      guanosine monophosphate levels in the cerebral arteries of treated animals
      compared with placebo (P < 0.05, unpaired t test). Thiocyanate was not present in
      significantly increased amounts in animals treated with nitroprusside, although
      this group did display elevated concentrations of nitrosyl hemoglobin (measured
      by electron paramagnetic resonance spectroscopy) and cyanomethemoglobin (measured
      by spectrophotometry) in the cerebrospinal fluid on Day 7. CONCLUSION: The lack
      of effect of sodium nitroprusside was not the result of inadequate drug delivery
      because cyclic guanosine monophosphate levels were significantly increased in
      vasospastic arteries. Vasospasm may not have been prevented because of a toxic
      effect of sodium nitroprusside metabolites, involvement of smooth muscle
      relaxation or contraction processes downstream of cyclic guanosine monophosphate,
      or both.

PMID- 12188958
TI  - Experimental radiofrequency brain lesions: a volumetric study.
AB  - OBJECTIVE: This study describes the production, under strictly standardized and
      controlled conditions, of radiofrequency lesions with identical neurogenerator
      settings: in vitro in two different albumin solutions (nongelatinous and
      gelatinous) and in vivo in the thalamus of the pig. METHODS: The radiofrequency
      lesions were investigated in vitro by the use of a specially designed video
      system and in vivo by magnetic resonance imaging. Moreover, the size of the in
      vivo lesions was estimated with the use of histological sectioning. The
      statistical analysis included the calculation of a correlation coefficient for
      the length, width, and volume for each lesion estimation. RESULTS: A high
      correlation (R = 0.96, P < 0.005; n = 14) was found between clot sizes in the two
      albumin solutions. Albumin clots generated in gelatinous albumin showed
      systematically larger volumes. In the pig, two concentric zones were seen in all
      magnetic resonance images and all histological preparations. The width
      correlation of the completely coagulated brain tissue (inner zones) was R = 0.94,
      P < 0.005, and n = 7. The corresponding correlation between magnetic resonance
      images and gelatinous albumin was R = 0.93, P < 0.005, and n = 7. As a rule, the
      in vitro clots were smaller than the outer zone but larger than the inner zone of
      the magnetic resonance imaging-recorded lesions for all of the electrode and
      temperature combinations tested. In vivo lesions generated with the same
      electrode and parameter settings showed high reproducibility. CONCLUSION: The
      value of presurgical electrode tests to validate the electrode function and
      lesion size in vitro has become evident in this study, which shows a high
      correlation between the in vitro albumin clots and the in vivo lesions observed
      on magnetic resonance images.

PMID- 12188959
TI  - Neurosurgery in Egypt: past, present, and future-from pyramids to radiosurgery.
AB  - THE CONTEMPORARY DEVELOPMENT of neurosurgery in Egypt is described, with
      reference to the ancient past and recent American and European influences. This
      article traces the steps taken by several leading Egyptian pioneers. Egypt, one
      of the key countries in the Middle East, has led the development of the specialty
      in the region and has maintained close ties with the international body of
      neurological surgeons and surgical societies.

PMID- 12188960
TI  - Cervical artery dissections: evidence for redissection in previously dissected
      arteries: report of three cases.
AB  - OBJECTIVE AND IMPORTANCE: Among patients with spontaneous internal carotid artery
      (ICA) or vertebral artery dissections, there is a small but significant risk of
      development of dissection in an uninvolved ICA or vertebral artery at some time
      in the future. Recurrence of dissection in a previously dissected and healed ICA
      or vertebral artery is very rare. We retrospectively reviewed more than 400 cases
      of cervical artery dissections in our cerebrovascular records for 1970 through
      2000. CLINICAL PRESENTATION: Three patients with recurrence of dissection in
      previously dissected and presumably healed ICAs were identified. All three
      patients were women. Their ages at the time of the initial dissection were 42,
      38, and 31 years. Initial ICA dissections were bilateral in all cases, occurring
      simultaneously in one case and 1 year apart in the other two cases. All
      dissections were spontaneous. Redissection of a previously dissected and healed
      ICA in these three patents occurred 11, 6, and 12 years later, respectively. Two
      patients had fibromuscular dysplasia. CONCLUSION: Our experience with these three
      cases, from among more than 400 cases of cervical artery dissections treated at
      our institution, and the very limited number of reported cases in the literature
      indicate the rarity of recurrence of dissection in previously dissected and
      healed cervical arteries. An underlying arteriopathy may be suspected in many of
      these cases. Management requires medical and sometimes surgical approaches.

PMID- 12188961
TI  - Delayed rupture of a previously coiled unruptured anterior communicating artery
      aneurysm: case report.
AB  - OBJECTIVE AND IMPORTANCE: We describe a case of an unruptured anterior
      communicating aneurysm that was treated successfully with Guglielmi detachable
      coils, which subsequently ruptured 23 months after initial therapy. This report
      discusses only the second published case of an unruptured lesion that was well
      embolized (>95% occlusion) and stable at 6-month angiographic follow-up that
      ruptured in a delayed fashion almost 2 years after the primary procedure.
      CLINICAL PRESENTATION: An 80-year-old man presented in Hunt and Hess Grade IV as
      a result of a ruptured anterior communicating artery aneurysm. The patient had
      undergone endovascular therapy 23 months earlier with documented nearly complete
      (1-mm residual neck) occlusion at 0 and 6 months. INTERVENTION: The patient
      underwent diagnostic catheter angiography at the time of admission, which
      revealed a 10-mm aneurysm adjacent to the previously embolized lesion. No further
      therapy was administered, and the patient died within 24 hours as a result of
      ictus. The request for an autopsy was denied. CONCLUSION: Aneurysm rupture after
      Guglielmi detachable coil embolization is a rare event. Most cases involve
      previously ruptured lesions. To the best of our knowledge, only one previous case
      of delayed rupture of an unruptured aneurysm that was managed endovascularly has
      been published in the English-language literature. This second case points to the
      need for vigilance in the follow-up of patients with coiled lesions.

PMID- 12188962
TI  - Rare Actinobacillus infection of the cavernous sinus causing painful
      ophthalmoplegia: case report.
AB  - OBJECTIVE AND IMPORTANCE: Actinobacillus actinomycetemcomitans is a gram-negative
      coccobacillus that is known to cause a wide array of clinical infections in
      debilitated patients, including periodontal disease, soft tissue abscess, pleural
      empyema, endocarditis, cerebral abscess, and meningitis. We report a rare A.
      actinomycetemcomitans cavernous sinus abscess that caused painful ophthalmoplegia
      in a healthy man. CLINICAL PRESENTATION: A 34-year-old man presented with a 3
      month history of acute onset of left-sided retro-orbital pain that progressed to
      a complete left Cranial Nerve VI palsy and Cranial Nerve V1 and V2 hypesthesia.
      Magnetic resonance imaging revealed the presence of an enhancing lesion in the
      left cavernous sinus, which encased and narrowed the ipsilateral intracavernous
      segment of the internal carotid artery. Routine blood and cerebrospinal fluid
      analyses were normal. Tolosa-Hunt syndrome was suspected, and the patient was
      treated with high-dose corticosteroids. An open biopsy was performed after failed
      prolonged corticosteroid therapy. INTERVENTION: A left frontotemporal craniotomy
      and cavernous sinus exploration through an interdural approach were performed. A
      soft reddish mass was found in the cavernous sinus around Cranial Nerve V1 and
      V2. Multiple biopsies were obtained. Pathological analysis revealed a purulent
      infection containing multiple gram-negative coccobacilli. The patient's pain
      improved immediately, and cranial neuropathy resolved during the next several
      weeks. After cultures demonstrated growth of A. actinomycetemcomitans, a regimen
      of orally administered amoxicillin and metronidazole was initiated. Eight months
      after surgery, the patient was free of symptoms and a repeat magnetic resonance
      imaging scan was normal. CONCLUSION: We present a rare bacterial abscess of the
      cavernous sinus causing painful ophthalmoplegia. In patients who present with
      presumed Tolosa-Hunt syndrome and do not improve with prolonged high-dose
      corticosteroid therapy, an open biopsy is recommended to exclude a bacterial
      infection.

PMID- 12188963
TI  - Nasofrontal dermoid sinus cyst: report of two cases.
AB  - OBJECTIVE AND IMPORTANCE: Nasofrontal dermoid sinus cysts are rare. The
      embryological origin, presentation, treatment, and genetic associations of two
      cases of these cysts are discussed. Emphasis is placed on physical findings and
      the importance of addressing both the intracranial and extracranial components.
      CLINICAL PRESENTATION: The first patient, a 33-year-old woman, sought care for
      chemical meningitis. As a child, she was differentiated from her identical twin
      sister by a dimple on the tip of her nose. The second patient, a 34-year-old man,
      sought care for new-onset seizures. Since birth, he had a dimple on the tip of
      his nose. As a child, he had undergone resection of a nasal cyst. Imaging studies
      in both patients indicated a midline anterior cranial base mass within the falx
      and a defect in the crista galli. INTERVENTION: Both patients underwent
      biorbitofrontal nasal craniotomy. A bifrontal craniotomy was performed first,
      then removal of the orbitonasal ridge. The dermoid and involved falx were
      resected. The sinus tract was followed through the crista galli and resected up
      to the osteocartilaginous junction in the nose. The remainder of the tract was
      resected via a small incision through the nares. The dura was closed primarily by
      mobilizing the dura along the sides of the crista galli. After surgery, both
      patients still possessed their sense of smell. CONCLUSION: Nasofrontal dermoid
      sinus cysts have a unique embryological origin. A midline basal frontal dermoid
      associated with a dimple on the nasal surface with or without protruding hair and
      sebaceous discharge is the pathognomonic presentation. It is important to address
      both the intracranial and extracranial component surgically. Although concomitant
      anomalies and familial clustering have been described, most cases are spontaneous
      occurrences.

PMID- 12188964
TI  - Fibrous dysplasia in combination with aneurysmal bone cyst of the occipital bone
      and the clivus: case report and review of the literature.
AB  - OBJECTIVE AND IMPORTANCE: Fibrous dysplasia of the cranium is a relatively
      uncommon disorder that affects primarily the anterior cranial region; its
      occurrence in the cranial base in combination with aneurysmal bone cyst (ABC)
      constitutes an extremely rare condition, only two cases of which have been
      reported previously in the literature. It is important to recognize and treat
      these cases properly because of the special location in the cranial base and the
      possibility of neural structure impingement. CLINICAL PRESENTATION: We report the
      case of a 19-year-old man with a slowly enlarging mass of the occiput, with
      computed tomographic and magnetic resonance imaging revealing involvement of
      petrous and basisphenoid bone and growing ABC. INTERVENTION: Open biopsy
      confirmed the diagnosis of fibrous dysplasia. Partial excision of the lesion and
      removal of the ABC were performed in a second stage after embolization.
      CONCLUSION: ABC associated with fibrous dysplasia of the cranial base may enlarge
      rapidly after puberty and require excision. This is facilitated by preoperative
      embolization.

PMID- 12188965
TI  - Unusual migration of the distal catheter of a ventriculoperitoneal shunt into the
      heart: case report.
AB  - OBJECTIVE AND IMPORTANCE: Placement of a ventriculoperitoneal (VP) shunt is the
      most common form of treatment for hydrocephalus. Thoracic complications with VP
      shunts are rare, but we present the second documented case of the distal
      migration of the distal catheter of a VP shunt into the heart. CLINICAL
      PRESENTATION: A 14-year-old boy, who underwent placement of a right occipital VP
      shunt at another institution after closed-head injury, presented with
      hypertension. Plain chest x-rays and computed tomography revealed the distal
      catheter to be in the right ventricle of the heart. INTERVENTION: A joint
      surgical procedure was performed with the cardiac surgery team. The cardiac
      surgeons created a pericardial window through a subxyphoid incision.
      Simultaneously, a right occipital incision was made to access the distal
      catheter, which was then slowly pulled out with the pericardium under direct
      visualization. No hemorrhage or change in the pericardium was observed, and,
      therefore, the need for a thoracotomy was eliminated. A new distal catheter was
      placed into the peritoneal cavity. CONCLUSION: The migration of the distal
      catheter probably occurred during the initial VP shunt placement. The internal
      jugular vein probably was perforated by the tunneler during the creation of the
      distal catheter tract. Slow venous flow and negative inspiratory pressure may
      have gradually pulled the catheter up into the right atria and ventricle. As
      demonstrated by our case report, the catheter can be extracted safely in a joint
      procedure with cardiac surgeons, and a thoracotomy is not always necessary. The
      patient did not experience postoperative complications, and his hypertension was
      alleviated.

PMID- 12188966
TI  - Acute foramen magnum syndrome caused by an acquired Chiari malformation after
      lumbar drainage of cerebrospinal fluid: report of three cases.
AB  - OBJECTIVE AND IMPORTANCE: The perioperative use of lumbar drainage of
      cerebrospinal fluid (CSF) is relatively common in neurosurgery, and the
      development of "acquired" Chiari malformations (tonsillar herniation) with lumbar
      CSF diversion procedures has been reported. CLINICAL PRESENTATION: We describe
      the history of three patients who developed a foramen magnum syndrome,
      attributable to acquired Chiari I malformations, after perioperative lumbar
      drainage of CSF. CONCLUSION: We propose that the mechanism responsible for Chiari
      I malformations involves a negative pressure gradient between the cranial and
      spinal regions, created by CSF drainage. Theories regarding the formation of
      acquired Chiari I malformations, the possible synergistic roles of intracranial
      pathological conditions and CSF drainage in the development of this entity, and
      the implications for the use of perioperative lumbar drainage are discussed.

PMID- 12188967
TI  - Intrathecal saline infusion in the treatment of obtundation associated with
      spontaneous intracranial hypotension: technical case report.
AB  - OBJECTIVE AND IMPORTANCE: Spontaneous intracranial hypotension is an increasingly
      recognized cause of postural headache. However, appropriate management of
      obtundation caused by intracranial hypotension is not well defined. CLINICAL
      PRESENTATION: A 43-year-old man presented with postural headache followed by
      rapid decline in mental status. Imaging findings were consistent with the
      diagnosis of spontaneous intracranial hypotension, with bilateral subdural
      hematomas, pachymeningeal enhancement, and caudal displacement of posterior fossa
      structures and optic chiasm. INTERVENTION: Despite treatment with lumbar epidural
      blood patch, worsening stupor necessitated intubation and mechanical ventilation.
      Contrast-enhanced magnetic resonance imaging and computed tomographic myelography
      of the spine failed to demonstrate the site of cerebrospinal fluid fistula. The
      enlarging subdural fluid collections were drained, and a ventriculostomy was
      performed. Postoperatively, the patient remained semicomatose. To restore
      intraspinal and intracranial pressures, intrathecal infusion of saline was
      initiated. After several hours of lumbar saline infusion, lumbar and intracranial
      pressures normalized, and the patient's stupor resolved rapidly. Repeat computed
      tomographic myelography accomplished via C1-C2 puncture demonstrated a large
      ventrolateral T1-T3 leak, which was treated successfully with a thoracic epidural
      blood patch. Follow-up magnetic resonance imaging demonstrated resolution of
      intracranial hypotension, and the patient was discharged in excellent condition.
      CONCLUSION: Spontaneous intracranial hypotension may cause a decline of mental
      status and require lumbar intrathecal saline infusion to arrest or reverse
      impending central (transtentorial) herniation. This case demonstrates the use of
      simultaneous monitoring of lumbar and intracranial pressures to appropriately
      titrate the infusion and document resolution of intracranial hypotension.
      Maneuvers aimed at sealing the cerebrospinal fluid fistula then can be performed
      in a less emergent fashion after the patient's mental status has stabilized.

PMID- 12188976
TI  - Mental health trauma response to the events of September 11th: challenges and
      lessons learned.

PMID- 12188977
TI  - Correlation of antipsychotic and prolactin concentrations in children and
      adolescents acutely treated with haloperidol, clozapine, or olanzapine.
AB  - Patients with a Diagnostic and Statistical Manual of Mental Disorders (third
      edition, revised) diagnosis of schizophrenia or psychotic disorder not otherwise
      specified with onset of psychosis before the age of 13 participated in 6- to 8
      week open or double-blind trials of haloperidol (n = 15, mean dose 15.4 +/- 8.1
      mg/day [0.27 +/- 0.15 mg/kg/day]), clozapine (n = 30, mean dose 269.9 +/- 173.3
      mg/day [4.4 +/- 2.6 mg/kg/day]), or olanzapine (n = 12, mean dose 17.5 +/- 2.8
      mg/day [0.30 +/- 0.13 mg/kg/day]). Blood samples were obtained at 6 weeks for
      evaluation of haloperidol, reduced haloperidol, clozapine, desmethylclozapine,
      and olanzapine plasma concentrations and serum prolactin concentrations. No
      gender differences were noted for antipsychotic dose or concentration within each
      treatment group. Correlations between antipsychotic plasma concentration and
      serum prolactin concentration were significant only for the olanzapine treatment
      group (r = 0.80, p = 0.002). Separate correlations for gender were significant
      only for females receiving olanzapine (r = 0.91, p = 0.03); the patient with the
      highest serum prolactin experienced galactorrhea. Further studies evaluating the
      prolactin-elevating properties of antipsychotics are warranted in this
      population.

PMID- 12188978
TI  - Clozapine in adolescent inpatients with acute mania.
AB  - Some bipolar patients with acute manic episodes can be refractory to conventional
      treatment with mood stabilizers. Clozapine, an atypical antipsychotic, has been
      reported to be effective in adults with treatment-resistant bipolar disorder. We
      describe the therapeutic effect of clozapine in 10 adolescent inpatients (12- to
      17-year-olds) with severe acute manic or mixed episodes who did not improve after
      treatment with conventional drugs (mood stabilizers, antipsychotics). At hospital
      discharge, 15 to 28 days after clozapine treatment, all patients had responded
      positively according to the Clinical Global Impression-Improvement Scale scores.
      The mean changes in Mania Rating Scale, Brief Psychiatric Rating Scale,
      Children's Global Assessment Scale, and Clinical Global Impression-Severity Scale
      were significant (p < 0.001). Clozapine dosage was 142.5 +/- 73.6 mg/day (range
      75-300 mg/day). Side effects (increased appetite, sedation, enuresis, sialorrhea)
      were frequent but not severe enough to require reduction of dosage. Mean weight
      gain after 6 months was 6.96 +/- 3.08 kg (10.7%). Neither decrease of white cells
      nor epileptic seizures were reported during follow-up (12-24 months). These
      preliminary findings suggest that clozapine may improve the clinical picture in
      adolescents with treatment-refractory manic or mixed episodes. Controlled studies
      on larger samples are warranted.

PMID- 12188979
TI  - Parsing the comorbidity between bipolar disorder and anxiety disorders: a
      familial risk analysis.
AB  - BACKGROUND: A growing literature suggests that anxiety disorders (ANX) co-occur
      with bipolar disorder (BPD), but the nature of this overlap is unknown. Thus, we
      investigated the familial association between BPD and ANX among the first-degree
      relatives of children with BPD with and without comorbid ANX. METHODS: We
      compared relatives of four proband groups defined by the presence or absence of
      BPD and ANX in the proband: (1) BPD + ANX (n = 23 probands, 74 relatives), (2)
      BPD without ANX (n = 11 probands, 38 relatives), (3) ANX without BPD (n = 48
      probands, 167 relatives), and (4) controls without BPD or ANX (n = 118 probands,
      385 relatives). All subjects were evaluated with structured diagnostic
      interviews. Diagnoses of relatives were made blind to the diagnoses of probands.
      RESULTS: The results show high rates of both BPD and ANX in relatives of children
      with BPD + ANX. Moreover, BPD and ANX cosegregated among the relatives of
      children with BPD + ANX. Although relatives of both ANX proband groups (with and
      without BPD) had high rates of ANX, and relatives of both BPD proband groups
      (with and without ANX) had high rates of BPD, the combined condition BPD + ANX
      was the predominant form of BPD among relatives of probands with BPD + ANX.
      CONCLUSIONS: These family-genetic findings suggest that the comorbid condition
      BPD+ANX may be a distinct clinical entity. More work is needed to evaluate
      whether the presence of comorbid ANX may be a marker of very early onset BPD.

PMID- 12188980
TI  - Screening for adolescent depression: comparison of the Kutcher Adolescent
      Depression Scale with the Beck depression inventory.
AB  - Self-report instruments commonly used to assess depression in adolescents have
      limited or unknown reliability and validity in this age group. We describe a new
      self-report scale, the Kutcher Adolescent Depression Scale (KADS), designed
      specifically to diagnose and assess the severity of adolescent depression. This
      report compares the diagnostic validity of the full 16-item instrument, brief
      versions of it, and the Beck Depression Inventory (BDI) against the criteria for
      major depressive episode (MDE) from the Mini International Neuropsychiatric
      Interview (MINI). Some 309 of 1,712 grade 7 to grade 12 students who completed
      the BDI had scores that exceeded 15. All were invited for further assessment, of
      whom 161 agreed to assessment by the KADS, the BDI again, and a MINI diagnostic
      interview for MDE. Receiver operating characteristic (ROC) curve analysis was
      used to determine which KADS items best identified subjects experiencing an MDE.
      Further ROC curve analyses established that the overall diagnostic ability of a
      six-item subscale of the KADS was at least as good as that of the BDI and was
      better than that of the full-length KADS. Used with a cutoff score of 6, the six
      item KADS achieved sensitivity and specificity rates of 92% and 71%, respectively
      a combination not achieved by other self-report instruments. The six-item KADS
      may prove to be an efficient and effective means of ruling out MDE in
      adolescents.

PMID- 12188968
TI  - Preliminary clinical experience with the Bryan Cervical Disc Prosthesis.
AB  - OBJECTIVE: The concept of accelerated degeneration of adjacent disc levels as a
      consequence of increased stress caused by interbody fusion of the cervical spine
      has been widely postulated. Therefore, reconstruction of a failed intervertebral
      disc with a functional disc prosthesis should offer the same benefits as fusion
      while simultaneously providing motion and thereby protecting the adjacent level
      discs from the abnormal stresses associated with fusion. This study was designed
      to determine whether a new, functional intervertebral cervical disc prosthesis
      can provide relief from objective neurological symptoms and signs, improve the
      patient's ability to perform activities of daily living, decrease pain, and
      provide stability and normal range of motion. METHODS: We conducted a
      prospective, concurrently enrolled, multicenter trial of the Bryan Cervical Disc
      Prosthesis (Spinal Dynamics Corp., Mercer Island, WA) for the treatment of
      patients with single-level degenerative disc disease of the cervical spine.
      Patients with symptomatic cervical radiculopathy and/or myelopathy underwent
      implantation with the Bryan prosthesis after a standard anterior cervical
      discectomy. At scheduled follow-up periods, the effectiveness of the device was
      characterized by evaluating each patient's pain, neurological function, and range
      of motion at the implanted level. RESULTS: Analysis included data regarding 60
      patients at 6 months with 30 of those patients at 1 year. Clinical success at 6
      months and 1 year after implantation was 86 and 90%, respectively, exceeding the
      study's acceptance criteria of 85%. These results compare favorably with the
      short-term clinical outcomes associated with anterior cervical discectomy and
      fusion reported in the literature. At 1 year, there was no measurable subsidence
      of the devices (based on a measurement detection threshold of 2 mm). Evidence of
      anterior and/or posterior device migration was detected in one patient and
      suspected in a second patient. There was no evidence of spondylotic bridging at
      the implanted disc space. The measured range of motion in flexion-extension, as
      determined by an independent radiologist, ranged from 1 to 21 degrees (mean range
      of motion, 9 +/- 5 degrees). No devices have been explanted or surgically
      revised. CONCLUSION: Discectomy and implantation of the device alleviates
      neurological symptoms and signs similar to anterior cervical discectomy and
      fusion. Radiographic evidence supports normal range of motion. The procedure is
      safe and the patients recover quickly. Restrictive postoperative management is
      not necessary. However, only after long-term follow-up of at least 5 years will
      it become clear whether the device remains functional, thus confirming these
      early favorable results. In addition, the influence on adjacent motion segments
      can be assessed after at least 5 years of follow-up.

PMID- 12188981
TI  - Caffeine use and dependence in adolescents: one-year follow-up.
AB  - The objectives were to conduct a 1-year follow-up of daily caffeine-using
      adolescents to further describe caffeine dependence symptoms and to determine
      whether caffeine dependence is associated with other substance dependence
      disorders. Twenty-one of 36 (58.3%) adolescents who participated in a study of
      caffeine dependence returned for follow-up. The previous study was a case series
      of adolescents who consumed caffeine daily and met some Diagnostic and
      Statistical Manual of Mental Disorders (fourth edition) substance dependence
      criteria as applied to caffeine. At follow-up, caffeine consumption from
      beverages was 179.9 +/- 151.8 mg/day. Of the 21 teenagers, 23.8% (n = 5) met
      criteria for caffeine dependence. Four of these participants developed caffeine
      dependence during the follow-up period. Other substance dependence disorders were
      not overrepresented in the caffeine dependent group compared to the caffeine
      nondependent group. The most commonly reported withdrawal symptoms in dependent
      teenagers (at baseline and follow-up combined) were feeling drowsy/tired,
      fatigued, or sluggish/slowed down (83.3% each) and headache (75.0%). Caffeine
      dependence occurs in some adolescents who drink caffeine daily and is marked by
      symptoms similar to those found in adults.

PMID- 12188982
TI  - Side effects of desipramine and age.
AB  - INTRODUCTION: The treatment response of children and adolescents to tricyclic
      antidepressants differs from that of adults. Few data exist on the impact of age
      on side effects. This study compares desipramine-associated side effects in
      children, adolescents, and adults. METHODS: Data from three trials of desipramine
      were combined to produce a sample of 148 subjects, aged 7 to 66 years. Pulse and
      blood pressure were measured at baseline and while participants were receiving
      desipramine. Side effects were rated by a clinician. For data analysis, subjects
      were divided into two groups, younger patients (18 and younger) and older
      patients (19 and older). Group means of side effect ratings and vital signs were
      compared. Results were also analyzed covarying for plasma levels of desipramine.
      RESULTS: There were significant differences between younger and older patients in
      pulse and blood pressure at baseline, on desipramine, and in changes in vital
      signs between baseline and medicated states. Younger patients had significantly
      lower mean ratings for constipation and dry mouth. DISCUSSION: Treatment with
      desipramine results in differing degrees of subjective side effects and changes
      in vital signs across the life cycle. Physicians should not assume that side
      effects experienced by children and adolescents are identical to those
      experienced by adults.

PMID- 12188983
TI  - Psychopharmacological treatment of child and adolescent psychiatric inpatients in
      Finland.
AB  - OBJECTIVE: The objective of this study was to investigate the use of
      psychopharmacological treatment in child and adolescent psychiatric inpatient
      treatment in Finland. METHODS: The study is a cross-sectional study conducted in
      January 2000. The psychiatrist responsible for the inpatient treatment was asked
      to fill in a questionnaire for every inpatient who occupied a child or adolescent
      psychiatric bed during the chosen study day (n = 504 patients). Information on
      psychopharmacological treatment was obtained for 475 patients. RESULTS: Forty
      three percent had scheduled medication and 28% had "as required" medication. Of
      those with scheduled medication, 56% had neuroleptics and 45% antidepressants. In
      multivariate analysis, older age (13-18 years), involuntary treatment, and
      psychotic disorder were independently associated with scheduled medication,
      neuroleptic treatment, and as required medication prescription. Neurolepic
      treatment was also associated with a very low general functioning level
      (Children's Global Assessment Scale < 41). A diagnosis of depression and older
      age were associated with antidepressant treatment. Almost all patients with
      antidepressant treatment were treated with selective serotonin reuptake
      inhibitors. CONCLUSIONS: Compared with data from a similarly conducted study in
      1988, there is an increase especially in the use of antidepressant medication in
      inpatient care. Considering the increasing use of psychopharmacotherapy during
      the last 10 years as shown in the present study, the lack of research-based data
      on the efficacy and safety supporting their clinical use is a major problem in
      the treatment of disabling childhood mental health problems.

PMID- 12188984
TI  - Is parental report of upper respiratory infection at the onset of obsessive
      compulsive disorder suggestive of pediatric autoimmune neuropsychiatric disorder
      associated with streptococcal infection?
AB  - The diagnosis of pediatric autoimmune neuropsychiatric disorder associated with
      streptococcal infection (PANDAS) requires a prospectively determined association
      between group A beta-hemolytic streptococcal (GABHS) infection and obsessive
      compulsive disorder (OCD) or tic disorder. Screening for GABHS infection imposes
      a significant burden on both patient and clinician. To heighten the index of
      suspicion for PANDAS, it would be useful to know if parent-reported upper
      respiratory infection (URI) is associated with PANDAS symptoms or associated
      characteristics. Eighty-three consecutive, clinically referred patients aged 6 to
      17 years with a primary diagnosis of OCD and their primary caregivers were asked
      about URI signs and symptoms at the time of OCD onset, PANDAS symptoms, OCD and
      tic symptoms, comorbidity, and putative PANDAS risk factors. Specific inquiry
      regarding URI symptoms proved more informative than general inquiry. In the URI
      present versus URI absent group, more patients experienced a sudden rather than
      insidious onset of symptoms. Additionally, more patients with a URI plus sudden
      onset exhibited a comorbid tic disorder. Until validated biomarkers permit
      retrospective diagnosis, a history that OCD began around the time of a URI should
      clue the clinician to look prospectively for PANDAS. Additional research is
      required to define the boundaries of PANDAS and to develop psychometrically
      reliable and valid diagnostic strategies.

PMID- 12188985
TI  - Case series: Adderall augmentation of serotonin reuptake inhibitors in childhood
      onset obsessive compulsive disorder.
AB  - Current pharmacological treatment of obsessive compulsive disorder involves the
      use of selective serotonin reuptake inhibitors (SSRIs). However, a large
      proportion of patients does not respond fully to these medications despite
      receiving optimal doses and concomitant cognitive-behavioral therapy. Finding
      efficacious augmentation strategies has become an important goal of researchers
      and clinicians working with this population. In this case series, we describe
      four patients with childhood-onset obsessive compulsive disorder, and with
      partial or no response to SSRI treatment, who subsequently had a reduction of
      their symptoms with Adderall augmentation.

PMID- 12188987
TI  - Nicotine addiction, young adults, and smoke-free bars.

PMID- 12188988
TI  - Six-month outcomes associated with a brief alcohol intervention for adult in
      patients with psychiatric disorders.
AB  - The objective of this study was to evaluate the 6-month outcomes of a brief
      intervention to reduce alcohol consumption by psychiatric in-patients in the
      general hospital setting and following resolution of psychiatric morbidity.
      Patients from the psychiatric wards of three general hospitals were screened
      using the Alcohol Use Disorders Identification Test. Of 144 people approached who
      matched the study criteria, 120 (83%) people aged 18-64 years (mean 31.7) were
      recruited. Participants were randomized to either a brief motivational interview
      or an information package to reduce alcohol consumption. Alcohol consumption was
      assessed as total weekly consumption and categorized on Australian National
      Health and Medical Research Council (NH&MRC) criteria. We delivered 62
      motivational interviews and 58 information packages. At the 6-month follow-up 83
      (69%), participants were reassessed. Both groups had significantly reduced
      alcohol consumption. However, the motivation group had a significantly greater
      reduction in weekly consumption than the information group (F = 6.8, (1,65) p <
      0.025) after controlling for age, sex, SCL-90-R GSI and alcohol dependence (and
      baseline alcohol consumption). A greater proportion of the motivation group
      compared to the information group also 'improved' in their classification on
      NH&MRC criteria (chi(2) = 7.3, df 1, p < 0.01). Brief interventions, especially
      motivational interviews, are effective in reducing alcohol use in persons with
      psychiatric disorders. They are effective across the mid-range of GSI severity
      scores for in-patients. Screening and brief interventions can and should be
      incorporated into the routine assessment and management in psychiatric units.

PMID- 12188989
TI  - Prevalence of responsible hospitality policies in licensed premises that are
      associated with alcohol-related harm.
AB  - This study aimed to determine the prevalence of responsible hospitality policies
      in a group of licensed premises associated with alcohol-related harm. During
      March 1999, 108 licensed premises with one or more police-identified alcohol
      related incidents in the previous 3 months received a visit from a police
      officer. A 30-item audit checklist was used to determine the responsible
      hospitality policies being undertaken by each premises within eight policy
      domains: display required signage (three items); responsible host practices to
      prevent intoxication and under-age drinking (five items); written policies and
      guidelines for responsible service (three items); discouraging inappropriate
      promotions (three items); safe transport (two items); responsible management
      issues (seven items); physical environment (three items) and entry conditions
      (four items). No premises were undertaking all 30 items. Eighty per cent of the
      premises were undertaking 20 of the 30 items. All premises were undertaking at
      least 17 of the items. The proportion of premises undertaking individual items
      ranged from 16% to 100%. Premises were less likely to report having and providing
      written responsible hospitality documentation to staff, using door charges and
      having entry/re-entry rules. Significant differences between rural and urban
      premises were evident for four policies. Clubs were significantly more likely
      than hotels to have a written responsible service of alcohol policy and to
      clearly display codes of dress and conditions of entry. This study provides an
      indication of the extent and nature of responsible hospitality policies in a
      sample of licensed premises that are associated with a broad range of alcohol
      related harms. The finding that a large majority of such premises appear to adopt
      responsible hospitality policies suggests a need to assess the validity and
      reliability of tools used in the routine assessment of such policies, and of the
      potential for harm from licensed premises.

PMID- 12188990
TI  - Estimated alcohol-caused deaths in Australia, 1990-97.
AB  - The purpose of the study was to provide updated estimates of alcohol-caused
      mortality rates in Australia between 1990 and 1997, making adjustments for
      changes in the prevalence of high-risk alcohol use estimated on the basis of per
      capita alcohol consumption (PCAC). Deaths wholly and partially attributable to
      high-risk alcohol consumption were extracted from the Australian Bureau of
      Statistics Mortality Datafile (1990-1997) and multiplied by specific aetiological
      fractions, which in turn were adjusted by changes in the prevalence of high-risk
      alcohol use estimated on the basis of annual changes in PCAC. The yearly trends
      in age-standardized rates of estimated alcohol-caused deaths were compared with
      those using (i) aetiological fractions unadjusted for changes in PCAC, and (ii)
      wholly alcohol-caused conditions only (thus requiring no application of
      aetiological fractions). The age-standardized rates of all alcohol-caused deaths
      among males aged 15+ years declined from 1990 (4.01/10,000) to 1993 (3.19/10,000)
      and decreased far more slowly up to 1997 (3.15/10,000) - 16% overall. For
      females, these rates declined steadily from 1990 (1.75/10,000) to 1997
      (1.33/10,000) - 19% overall. Similar patterns in time trends were noted for
      estimated alcohol-caused death rates calculated as in (i) and (ii). However, the
      proportional decreases in rates (21.6% for males; 24.0% for females) would have
      been underestimated by 16% (males) and 19% (females) if the alcohol aetiological
      fractions had not been adjusted to take account of the estimated annual changes
      in the prevalence of high-risk drinking. The declines in estimated alcohol-caused
      death rates were more pronounced than the 9% decline in PCAC, and were due mainly
      to decreasing death rates for stroke (men and women), alcoholic liver cirrhosis
      and road injuries (men only). When aetiological fractions are used to measure
      temporal trends in estimated alcohol-caused death rates from official mortality
      statistics, they should account for annual changes in the prevalence of high-risk
      drinking. Such changes in prevalence can be deduced from yearly fluctuations in
      PCAC.

PMID- 12188991
TI  - Methadone-related deaths and mortality rate during induction into methadone
      maintenance, New South Wales, 1996.
AB  - The aims of this study were to describe the causes of death in cases found
      positive for methadone post-mortem, the proportion of cases involving methadone
      syrup, and of this group, the proportion not registered in methadone maintenance
      treatment (MMT) at time of death, and the number of deaths during induction into
      MMT in New South Wales in 1996. Coronial files of cases were reviewed. Data on
      file with the Pharmaceutical Services Branch, NSW Health Department on number of
      people admitted to and discharged from MMT in 1996, and details of methadone
      treatment for cases in MMT, were examined. Eighty-seven methadone positive cases
      were identified, of which 62 (71%) died of drug-related causes. Of 9835 people
      inducted into MMT in 1996, seven died within the first 7 days (21% of all deaths
      in MMT), for an overall mortality rate (MR) of 7.1 deaths per 10,000 inductions
      (95% CI 1.8-12.4). Fifty-one per cent (51%) of methadone syrup-related cases
      occurred in people not registered in MMT. This high proportion of diversion
      related deaths continues to be of concern. The findings reinforce to providers of
      MMT the necessity of careful procedures for initiation of treatment and support
      the need for ongoing surveillance of methadone related deaths both in and out of
      MMT.

PMID- 12188992
TI  - Knowledge and perception of risk for HIV and condom use among male injecting drug
      users in Cebu City, Philippines.
AB  - Injecting drug users (IDU) represent a small fraction of the HIV and AIDS cases
      in the Philippines. To determine if these people are engaging in behaviors that
      put them at risk for HIV, interviews were conducted with 360 male IDUs in Cebu
      City, Philippines, from 1997 to 1999, as part of a national surveillance system.
      The interviews assessed knowledge about HIV transmission, sources of information
      about HIV/AIDS, perceived risks of contracting HIV, needle-sharing practices,
      condom use, self-reported signs and symptoms of STDs and number of sex partners.
      Although most of the men were able to recognize behaviors accurately that put
      them at risk for HIV, more than two-thirds claimed that they shared needles and
      almost two-thirds of those who were sexually active claimed that they never used
      condoms. Intervention strategies must be developed for this population if the
      nation is to avoid the dramatic increase in HIV infection among IDUs that has
      been witnessed in neighboring Southeast Asian nations such as Malaysia and
      Vietnam.

PMID- 12188993
TI  - A 'demand side' estimate of the dollar value of the cannabis black market in New
      Zealand.
AB  - The dollar value of an illicit drug market is an important statistic in drug
      policy analysis. It can be used to illustrate the scale of the trade in a drug;
      evaluate its impact on a local community or nation; provide an indication of the
      level of criminality related to a drug; and can inform discussions of future drug
      policy options. This paper calculates the first ever demand side estimates of the
      New Zealand cannabis black market. The estimates produced are calculated using
      cannabis consumption data from the Alcohol & Public Health Research Unit's
      (APHRU) 1998 National Drug Survey. The wholesale value of the market is estimated
      to be 81.3-104.6 million dollars a year, and the retail value of the market is
      estimated to be 131.3-168.9 million dollars a year. These demand side estimates
      are much lower than the existing supply side estimates of the market calculated
      using police seizures of cannabis plants. The retail figure is four times lower
      than the lowest national supply side estimate (636 million dollars) and seven
      times lower than the highest national supply side estimate (1.27 billion
      dollars). The demand side estimates suggest a much smaller cannabis economy to
      fuel organized criminal activity in New Zealand than previous estimates implied.

PMID- 12188994
TI  - Community-based drug and alcohol counselling: who attends and why?
AB  - In order to develop and tailor treatment approaches in drug and alcohol
      counselling accurately, it is necessary to identify characteristics of the
      relevant client group. This study describes the demographic and substance use
      characteristics of 1212 community-based drug and alcohol counselling clients from
      a regional Area Health Service in NSW, Australia. Findings identify these clients
      as predominantly young, unmarried, unemployed males with low incomes. Alcohol use
      is characterized by binge consumption (83%) and alcohol-related problems (94%). A
      substantial proportion use tobacco (74%), cannabis (61%), opiates (15%) and
      amphetamines (22%). Of those using illicit drugs other than marijuana, the
      incidence of sharing syringes (10%) is of concern. These data differ from those
      reported by both general practice patients in the same geographical area, as a
      treatment-seeking population in an alternative community-based setting, and a
      general community sample. It is argued that there is a need for interventions
      delivered in community-based drug and alcohol settings that are aimed
      specifically at polydrug use, attempt to minimize drug-related harm and are
      relevant to those of lower socio-economic status.

PMID- 12188996
TI  - Women's alcohol consumption: emerging patterns, problems and public health
      implications.
AB  - There is growing awareness of changes in the levels and patterns of women's use
      of alcohol. Australian and international data suggest that patterns of
      consumption among younger women are beginning to echo that of their male
      counterparts. Similarly, alcohol consumption among older women is also increasing
      in some developed countries. This paper provides an overview of available data
      sources that address changing patterns of consumption among women in Australia,
      and explanatory models which may account for these changes are discussed.
      Particular attention is directed to drinking among younger women and indigenous
      women. External social factors are explored, including the erosion of traditional
      values associated with women's consumption of alcohol. Finally, the paper
      examines the evidence for a long speculated 'convergence' of female and male
      alcohol consumption and assesses the public health implications of the emerging
      patterns of alcohol consumption by women. The inconsistent findings regarding
      brief interventions when applied to women, compared to men, are also highlighted
      in terms of appropriate future public health strategies.

PMID- 12188995
TI  - Focus groups with pregnant smokers: barriers to cessation, attitudes to nicotine
      patch use and perceptions of cessation counselling by care providers.
AB  - Focus group methodology was used to determine the barriers to smoking cessation
      for pregnant women prior to the commencement of a randomised controlled smoking
      cessation trial (RCT), using nicotine patches in the treatment arm. Attitudes to
      the use of nicotine patches and perceptions of care provider counselling were
      also explored. Women were identified by researcher interview in the antenatal
      clinics as current smokers or recent 'quitters' and recruited to one of three
      focus groups. A number of barriers to achieving smoking cessation were
      identified. Pregnancy-specific barriers included scepticism about smoking-related
      harms. Other barriers, such as addiction to nicotine and the smoking behaviour of
      others, particularly partners, are generic. The latter is magnified in pregnancy
      by the heightened complexities of familial relationships. Potential use of
      patches was acceptable to most women, although some high-risk patients expressed
      doubts about safety and believed continued smoking was preferable. Women
      recounted that care providers differed in approaches to smoking cessation.
      Reporting 'cutting down' generally avoided further inquiries about smoking. The
      knowledge gained of pregnant women's perspectives enhanced the researchers'
      understanding in these areas. These insights have been incorporated into staff
      training initiatives, have guided the planning of the RCT, and have continued to
      inform its conduct.

PMID- 12188998
TI  - Taxation, supply control, and prisoners.

PMID- 12188997
TI  - Substitution therapy for amphetamine users.

PMID- 12188999
TI  - Celebrating 20 years of the Drug and Alcohol Review.

PMID- 12189000
TI  - Factors associated with continued smoking during pregnancy: analysis of socio
      demographic, pregnancy and smoking-related factors.
AB  - This study investigated the characteristics associated with smoking during
      pregnancy. A total of 7836 pregnant women were surveyed between 1992 and 1999 in
      England. Of these 27% were smoking during pregnancy. Pregnant women were more
      likely to smoke if they were less educated, living in rented accommodation, in
      unskilled manual or unemployed groups, and single or had a partner who smokes.
      Analysed by logistic regression, whether or not a pregnant women has a partner
      and, if so, his smoking status, was by far the biggest predictor of the pregnant
      woman's current smoking status. Thus, compared with women with partners who never
      smoke, the odds ratio (OR) of smoking during pregnancy for women with a partner
      who smokes was 2.3 (1.9-2.7) while those with no partner had an OR of 4.8 (3.8
      6.0). For women exposed to passive smoke at home or at work the OR was 2.5 (2.1
      3.0). Housing tenure was the most important socio-demographic predictor. Thus
      pregnant women living in rented council housing were nearly twice as likely (OR
      1.93;1.63-2.29) as those buying their own home to be current smokers. The number
      of women who continued to smoke during pregnancy increased 10-fold from the least
      to the most deprived group. These findings highlight the importance of tobacco
      control strategies that address pregnant women's life circumstances and broader
      inequalities as well as those that focus on individual smoking behaviour.

PMID- 12189001
TI  - The injection of methadone and benzodiazepines among Sydney injecting drug users
      1996-2000: 5-year monitoring of trends from the Illicit Drug Reporting System.
AB  - Trends in the injection of methadone and benzodiazepines by injecting drug users
      (IDU) recruited in Sydney for the Illicit Drug Reporting System over the period
      1996-2000 were examined. A total of 788 IDU were interviewed over the 5-year
      period. The proportion of IDU reporting recent methadone injecting declined
      significantly over the study period, from a peak of 31% in 1997 to 13% in 2000.
      Unlike the injection of methadone, there was no significant difference between
      the proportions of IDU reporting recent benzodiazepine injecting over the study
      period, which ranged between 10% and 16%. A consistent minority (range 5-7%) of
      IDU reported having injected both methadone and benzodiazepines in all years of
      the study. There were no differences in the proportions of males and females
      reporting recent methadone or benzodiazepine injecting in any individual year.
      Both methadone and benzodiazepine injecting were independently associated with
      higher levels of injection-related health problems. Given the substantial harms
      associated with these practices, continued monitoring of their prevalence is
      warranted.

PMID- 12189002
TI  - Peer-delivered hepatitis C testing and counselling: a means of improving the
      health of injecting drug users.
AB  - We hypothesized that providing injecting drug users (IDUs) with free hepatitis C
      testing and counselling at a needle and syringe programme (NSP) would be an
      effective model. Between August 1999 and January 2000, our peer outreach worker
      offered these services from a busy NSP in western Melbourne. Over 300 counselling
      episodes were provided, and 47 IDUs who were not tested in the previous 12 months
      were given tests and full pre- and post-test counselling, and were interviewed
      about reasons for not being tested, their knowledge of hepatitis C, and their
      risk behaviour. Twenty-eight IDUs (59.6%) tested antibody-positive, demonstrating
      the need to improve testing coverage and compliance with counselling
      requirements. Most were not tested because they did not think they were at risk,
      but their reported behaviour and antibody test results showed otherwise. Twenty
      people returned for a second interview, and improvements in their risk behaviour
      and knowledge of hepatitis C were detected. Our experience suggests that demand
      exists for hepatitis C testing and counselling of IDUs in Melbourne's western
      suburbs, that testing and counselling improve IDUs' ability to avoid harm, and
      that delivery of these services by a trained and experienced peer located at an
      NSP is an appropriate and effective model.

PMID- 12189003
TI  - Buprenorphine dosing regime in the management of out-patient heroin withdrawal.
AB  - This study aimed to establish a buprenorphine regime suitable for the short-term
      management of out-patient heroin withdrawal using an open-label, single-group
      case series. Eighteen dependent injecting heroin users underwent an 8-day
      withdrawal episode with supervised dosing of sublingual Subutex tablets.
      Buprenorphine doses were titrated daily over a 5-day period. Fifteen subjects
      (83%) completed the 5-day regime, and 14 (78%) completed the 8-day withdrawal
      episode. The mean doses ((SD) were 6.1 (1.2) mg on day 1; 9.6 (1.7) mg on day 2;
      10.1 (1.9) mg on day 3; 8.9 (2.0) mg on day 4; 4.1 (1.5) mg on day 5; and a total
      regime dose of 38.9 (5.8) mg. Withdrawal severity was mild, with minimal rebound
      upon the cessation of dosing. Five subjects reported no heroin use, and five
      subjects reported using on only one occasion during the 8 days. An out-patient
      buprenorphine regime is recommended.

PMID- 12189004
TI  - The Holyoake Codependency Index: further evidence of factorial validity.
AB  - The Holyoake Codependency Index (HCI) is a 13-item self-report scale that
      measures codependent traits. The HCI contains three subscales that correspond to
      key themes within the codependency literature and that were derived from factor
      analysis using a clinical sample of mainly females. The factor structure was
      subsequently replicated with an all-female general community sample. In this
      study the factor structure was replicated using a mixed-sex sample of 107
      undergraduate university students and 378 other people who were snowball sampled
      from the student sample, and was found to hold for both male and female
      participants.

PMID- 12189005
TI  - The health effects of ecstasy: a literature review.
AB  - Ecstasy (3,4-methylenedioxymethamphetamine, MDMA) is the third most used illicit
      drug, after cannabis and amphetamines. There has been considerable interest in
      the adverse effects of use, with particular attention given to a small number of
      deaths related to ecstasy use, and the neurotoxic effects of MDMA. This paper
      reviews case reports of adverse effects attributed to ecstasy use, and the
      findings of animal and human studies, so as to identify the health effects of
      ecstasy use, and factors contributing to their occurrence. The incidence of
      serious acute adverse events related to ecstasy is low. It is the
      unpredictability of those adverse events and the risk of mortality and
      substantial morbidity that makes the health consequences of ecstasy significant.
      Hyperthermia and hyponatraemia are the most significant acute adverse effects,
      and can occur even when MDMA is the only drug used. Ecstasy users should be aware
      of the importance of controlling body temperature and fluid intake, early signs
      of adverse effects, and the need to seek medical assistance promptly.
      Neurotoxicity is potentially the most significant long-term effect of ecstasy.
      The clinical implications of neurotoxicity are uncertain at this time, but short
      term memory impairment may be significant.

PMID- 12189006
TI  - Petrol sniffing in Aboriginal communities: a review of interventions.
AB  - Petrol sniffing (and other forms of inhalant misuse) occur within some Aboriginal
      communities across Australia. However, there is little documented information
      about the nature and combination of interventions that are most effective in
      addressing it. This article reviews published and unpublished literature relevant
      to petrol sniffing in Australian Aboriginal communities. A range of strategies
      which have been trialled previously are discussed under the categories of
      primary, secondary and tertiary intervention. We have adopted Zinberg's schema of
      'drug', 'set' and 'setting' in theorizing the mix of interventions most likely to
      reduce petrol sniffing. We argue that interventions should address as many as
      possible of these factors. Further, while no strategy is likely to succeed
      without strong support from local community members, governments also have an
      important role in addressing petrol sniffing. Consistent funding for strategies
      directly addressing petrol sniffing and co-ordinated government responses to the
      broader needs of Aboriginal young people and their communities are critical.

PMID- 12189007
TI  - Hypokalaemia in alcoholic patients.
AB  - Hypokalaemia is commonly found among the electrolyte abnormalities observed in
      chronic alcoholics. However, the underlying mechanisms of the decreased potassium
      levels are not well known. We undertook the present study to analyse the possible
      pathogenetic mechanisms of hypokalaemia in a large group of alcoholic patients (n
      = 127) admitted to our hospital for causes related to alcohol abuse. Serum
      potassium levels were significantly lower in alcoholic patients compared to the
      control population (3.8 + 1.1 mmol/l vs. 4.6 + 0.9 mmol/l). In 12 of these
      patients inappropriate kaliuresis was observed due mainly to the coexistent
      hypomagnesaemia. Two of the remaining four patients had a history of diarrhoea,
      while the other two had alcohol withdrawal syndrome with considerable respiratory
      alkalosis. Patients with hypokalaemia had hypomagnesaemia and respiratory
      alkalosis more commonly compared to the normokalaemic ones. We conclude that
      hypokalaemia is a relatively common electrolyte abnormality observed in alcoholic
      patients owing to various pathophysiological mechanisms. Among them,
      inappropriate kaliuresis due to the co-existent hypomagnesaemia predominates.

PMID- 12189008
TI  - Interview with Peter Baume.

PMID- 12189009
TI  - Alcohol marketing on the internet: new challenges for harm reduction.

PMID- 12189010
TI  - Exercise and training effects on platelets in health and disease.
AB  - In recent years the involvement of platelets dysfunction in atherogenesis and in
      the clinical complications from atherosclerosis has become more recognised.
      Systemic platelet-related thrombogenic factors have been shown to be involved in
      the initiation and progression of atherogenesis and plaque growth. Over the last
      two decades, interest has been heightened regarding the changes in platelet
      aggregation and functions that are associated with exercise in normal subjects
      and also patients, particularly those suffering from coronary artery disease.
      Although exercise effects on platelet aggregation and function in healthy
      individuals have been examined, the results reported have been conflicting, most
      likely due to methodological problems in the measurements of platelet aggregation
      and activation during and after exercise. However for patients suffering from
      coronary heart disease, the balance of evidence available would strongly suggest
      that platelet aggregation and function are increased with exercise. Several drugs
      are known to affect platelets, the most studied among them is aspirin. The
      evidence available would suggest that aspirin is ineffective in attenuating
      enhanced platelet aggregation and activation induced by exercise. Although the
      effects of physical training have been briefly investigated, available meagre
      evidence suggests that exercise on a regular basis is associated with favourable
      effects on platelets aggregation and activation in both men and women.

PMID- 12189011
TI  - Differential actions of naftopidil, doxazosin and nifedipine on platelet
      thromboxane generation and platelet-derived growth factor efflux in vitro.
AB  - We examined the effects of the alpha(1)-adrenoreceptor blockers naftopidil and
      doxazosin and the Ca(2+) antagonist nifedipine on platelet function with
      reference to stimulus-induced thromboxane (TxB(2)) generation and platelet
      derived growth factor (PDGF) efflux. Collagen (5 micro g/ml) caused a 12.5-fold
      increase in TxB(2) generation, from a basal level of 7.69 +/- 1.28 ng/10(8)
      platelets to 96.34 +/- 13.37 ng/10(8) platelets (P<0.001). Adrenaline (16 micro
      M) increased TxB(2) production 3-fold from 2.44 +/- 0.61 to 8.02 +/- 1.08
      ng/10(8) platelets (P<0.01). Adrenaline-induced TxB(2) generation was inhibited
      42.5 +/- 10.3% (P<0.05) and 81.8 +/- 7.5% (P<0.05) by 10 and 40micro M
      naftopidil, respectively. Collagen-stimulated TxB(2) generation was inhibited
      59.5 +/- 9.2% (P<0.01) by 40 micro M naftopidil and 53.7 +/- 11.3% (P<0.01) by 28
      micro M nifedipine. Doxazosin (7.5 and 30 micro M) did not influence adrenaline-
      or collagen-induced TxB(2) synthesis. Collagen increased PDGF efflux from 1.17 +/
      0.39 to 4.25 +/- 0.51 ng/10(8) platelets (P<0.01), whilst adrenaline raised
      concentrations from 1.08 +/- 0.19 to 5.37 + 1.02 ng/10(8) platelets (P<0.01).
      Naftopidil had no effect on collagen-induced PDGF release. Adrenaline-stimulated
      PDGF efflux was, however, inhibited 82.9 +/- 13.7% (P<0.001) and 125.7 +/- 16.3%
      (P<0.001) by 10 and 40 micro M naftopidil, respectively. Doxazosin (30 micro M)
      inhibited adrenaline-induced PDGF release by 70.3 +/- 31.5% (P<0.05), whilst
      nifedipine (28 micro M) had no effect on collagen-stimulated release. We conclude
      that naftopidil, like nifedipine, may block stimulated TxB(2) generation via
      inhibition of phospholipase A(2), the Ca(2+)-dependent, rate-limiting enzyme in
      thromboxane synthesis. Although adrenaline-induced PDGF release was inhibited by
      naftopidil and doxazosin, collagen-induced release was unaffected by either
      alpha(1)-adrenoreceptor blocker or nifedipine, indicating that platelet alpha
      granular release is not dependent on Ca(2+) mobilisation or thromboxane
      generation. Thus, the effects of these drugs on PDGF release may be mediated
      through alternative cellular signalling mechanisms.

PMID- 12189012
TI  - Platelet activity, sensitivity to agonist, and platelet--leukocyte conjugate
      formation after long-term exercise.
AB  - For rehabilitation training it is recommended that the intensity of exercise
      should be distinctly below the individual anaerobic threshold (IAT). We
      investigated platelet activity, reactivity and platelet-leukocyte conjugate
      formation following a stardardized treadmill (TR) ergometer test at 90% IAT for
      60-120 min. Seventeen healthy male non-smokers underwent TR. Blood samples were
      taken after a 30-min rest, immediately after exercise, and 2 h after exercise
      completion. Platelets were detected flow cytometrically by CD41 in whole blood,
      activated platelets by CD62P. In addition, stimulation of platelets in vitro with
      7.5 microM TRAP-6 was performed. For testing platelet-leukocyte conjugates,
      antibodies against CD45 and CD41 were used. After TR the percent of non
      stimulated CD62P-positive platelets (%PC) remained unchanged (1.65 +/- 0.56 to
      1.73 +/- 0.79%PC) (mean +/- SD). In contrast, an increase (P<0.05) from 31.9 +/-
      13.5 to 37.4 +/- 15.0 %PC in CD62P, TRAP-6 stimulated and enhanced (P<0.01)
      platelet-leukocyte conjugates (11.7 +/- 3.7 to 16.1 +/- 6.9, CD41-%PC) after TR
      were observed. Both changes were independent of thrombin generation measured by
      F1+2 and TAT, and reversible after 2 h. Long-term exercise (90% IAT) on a
      treadmill ergometer only leads to a moderate increase of platelet reactivity and
      platelet-leukocyte conjugates. The determination of platelet-leukocyte conjugates
      may offer the possibility to detect an early activation stage of platelets in
      vivo.

PMID- 12189013
TI  - Identification of minor metabolites of phospholipid signal molecules in
      [(32)P]P(i)-labelled platelets.
AB  - Incubation of blood platelets with (32)P-labelled inorganic phosphate for 60 min
      leads to incorporation of radioisotope mainly into phosphatidylinositol (PI),
      phosphatidylinositol-4-phosphate (PIP) and phosphatidyl-4,5-bisphosphate (PIP(2))
      in resting platelets and into phosphatidic acid (PA) in activated platelets.
      Small amounts of other important phosphoinositide isomers also become labelled
      following platelet activation, among them the 3-phosphorylated derivatives. In
      addition, several other faintly labelled spots are visible on TLC separations.
      Three of these lipids have now been identified as lysophosphatidylinositol
      (lysoPI), lysophosphatidic acid (lysoPA) and CDP-diacylglcerol (CDP
      DAG).[(32)P]LysoPI was present in resting and activated platelets, whereas
      [(32)P]lysoPA and [(32)P]CDP-DAG were observed only upon platelet activation. The
      phosphoinositide cycle turns over without accumulation of [(32)P]PA and
      [(32)P]CDP-DAG in resting platelets. A large increase (as much as 40-fold) in the
      steady-state level of [(32)P]PA is seen in thrombin-activated platelets. A slight
      increase in the steady-state levels of [(32)P]CDP-DAG is accompanied by a similar
      increase in [(32)P]PI and larger increases in [(32)P]PIP and [(32)P]PIP(2) (about
      50%), which is indicative of a general increase in flux in the PPI cycle.
      Elevation of CDP-DAG levels is probably only a reflection of increased flux,
      whereas lysoPA and lysoPI have been reported to have diverse signalling functions
      in various cells.

PMID- 12189014
TI  - Effects of P2Y(1) and P2Y(12) receptor antagonists on ADP-induced shape change of
      equine platelets: comparison with human platelets.
AB  - Platelet activation by adenosine 5' -diphosphate (ADP) is via both P2Y(1 )and
      P2Y(12) receptors and leads to shape change and aggregation. The effects on ADP
      induced platelet shape change of two P2Y(1) antagonists, adenosine 3'-phosphate,
      5'-phosphosulfate (A3P5PS) and 2-deoxy-N(6)-methyladenosine 3', 5'-diphosphate
      (MRS-2179) and a P2Y(12) antagonist 2-propylthio-D-beta,gamma-dichloromethylene
      adenosine 5'-triphosphate (AR-C67085MX) were determined by turbidimetric
      aggregometry and scanning electron microscopy (SEM) on equine and human
      platelets. The platelet aggregation was inhibited during aggregometry by 4-[4
      [4(aminoiminomethyl)phenyl]-1-piperazinyl]-1-piperidin acid hydrochloride
      trihydrate (GR 144053F), an inhibitor of fibrinogen binding. From aggregation
      profiles, concentration-response curves and SEM we conclude that the shape change
      of equine platelets was susceptible to inhibition by the P2Y(1) antagonists
      A3P5PS and MRS-2179, but less so than human platelets. The P2Y(12) antagonist AR
      C67085 did not influence significantly the shape change of either equine or human
      platelets.

PMID- 12189015
TI  - Peroxynitrite-mediated modification of fibrinogen affects platelet aggregation
      and adhesion.
AB  - The reaction of peroxynitrite with fibrinogen resulted in both structural
      modifications and altered biological properties of this glycoprotein. SDS-PAGE
      analysis of peroxynitrite-treated fibrinogen, performed under non-reducing
      conditions, showed some aggregated material on the top of the gel (5-10% of total
      staining bands) and the presence of nitrotyrosine. The amount of nitrotyrosine,
      detected by immunoassay with anti-nitrotyrosine antibodies, was dependent on
      peroxynitrite concentration. In comparison with native molecule, peroxynitrite
      treated fibrinogen subjected to SDS-PAGE under reducing conditions revealed not
      only three bands corresponding to Aalpha, Bbeta and gamma chains, but the
      existence of additional high molecular bands probably due to the formation of
      dityrosine crosslinking between fibrinogen subunits. The different susceptibility
      in tyrosine nitration of fibrinogen subunits was also observed. The Aalpha chain
      was the most intensely nitrated, while Bbeta and gamma chains were nitrated much
      less? Peroxynitrite-treated fibrinogen in comparison with native molecule had a
      distinct capability to mediate platelet adhesion and aggregation. Both
      unstimulated and ADP-activated platelets showed a reduced ability to adhere to
      peroxynitrite-modified fibrinogen. The percentage of ADP-induced platelet
      aggregation decreased as a function of peroxynitrite-mediated modification of
      fibrinogen molecule.

PMID- 12189016
TI  - Mean platelet volume as an indicator of platelet activation: methodological
      issues.
AB  - BACKGROUND: Mean platelet volume (MPV) is increased in patients at high risk for
      athero-thrombotic diseases. Thus, an elevated MPV may be a risk marker for
      platelet activation. METHODS: Healthy subjects with normal triglyceride (TG)
      levels (90+/-6 mg/dl; n = 40) or mild hypertriglyceridemia (161+/-79 mg/dl; n =
      32) were studied. MPV was measured in fasting blood samples before and after
      stimulation with collagen (10 micro g/ml), and exposure to 4 or 37 degrees C.
      Samples from the normotriglyceridemic subjects were tested again 4 h after
      consuming a high-fat drink. RESULTS: Collagen and exposure to 4 degrees C
      increased MPV, whereas incubation at 37 degrees C lowered MPV regardless of TG
      level. There was no significant difference in unstimulated MPV between the
      fasting and the fed states in the normotriglyceridemic subjects (both 7.2+/-0.1
      fl; mean+/-SEM), nor between the latter group and hypertriglyceridemic subjects
      (7.0+/-0.1 fl). There was a significant negative relation between MPV and fasting
      TG level. CONCLUSIONS: This study suggests that MPV response to low-dose collagen
      may be a useful indicator of platelet propensity to activation. Further studies
      are warranted to correlate MPV with classical platelet aggregation tests and with
      the use of platelet-active drugs.

PMID- 12189017
TI  - Platelet cyclic GMP levels in unstable angina and myocardial infarction.
AB  - BACKGROUND: Several studies showed that there is a state of platelet
      hyperactivaction in patients with coronary syndrome: the aim of this study is to
      investigate if the platelet nitric oxide-cyclicGMP (NO-cGMP) pathway, that
      regulates platelet aggregation is altered in patients with unstable angina (UA)
      and acute myocardial infarction (AMI). METHODS AND RESULTS: Population included
      11 patients with UA, 12 patients with AMI and 23 controls. Platelet cGMP was
      measured by a radioimmunoassay kit, under basal conditions and after stimulation
      with sodium nitroprusside (SNP), which maximally stimulates soluble guanylate
      cyclase (sGC), used as an indirect measurement of active sGC. Basal platelet cGMP
      values were significantly (P<0.001) higher in patients with UA and AMI than in
      controls (UA, 1089 +/- 412 pmol/10(10) platelets; AMI, 1071 +/- 507 pmol/10(10)
      platelets; controls, 492 +/- 201 pmol/10(10) platelets). The final cGMP level
      reached after SNP stimulation was significantly more elevated in UA, compared
      with both AMI (P<0.05) and controls (P<0.02) (UA, 4428 +/- 2723 pmol/10(10)
      platelets; AMI, 2728 +/- 655 pmol/10(10) platelets; controls, 2772 +/- 1031
      pmol/10(10) platelets); on the contrary no significant difference between AMI and
      controls was observed. CONCLUSIONS: Basal platelet cGMP is significantly higher
      in both UA and AMI groups. This observation suggests that: (1) platelet-derived
      NO synthesis may be enhanced inUA and AMI, due to increase of intraplatelet
      calcium level and of platelet cNOS activation; (2) platelets from UA and AMI
      patients are continuously stimulated by the high-level NO production due to
      increased iNOS expression. As far as SNP-dependent cGMP production is concerned,
      UA and AMI behave as two separate conditions. SNP-stimulated activity in UA is
      higher than in controls, while a loss of functional sGC is observed in AMI.

PMID- 12189019
TI  - Electron dense chains and clusters in human platelets.
AB  - Human platelets contain dense organelles that serve as storage sites for adenine
      nucleotides and serotonin. They also contain calcium and phosphate responsible
      for the opacity of dense bodies in the electron microscope. The present study has
      shown that there are also bead-like structures and clusters of beads that are
      electron opaque when viewed by the whole mount technique. Their origin and
      function are not known. However, their presence might interfere with the accuracy
      of imaging techniques currently being used to measure the number and volume of
      dense bodies in patients with platelet storage pool deficiency.

PMID- 12189018
TI  - Platelet reactivity in spontaneously diabetic rats is independent from blood
      glucose and insulin levels.
AB  - Diabetes is associated with thrombotic disorders. Chemically induced and
      spontaneously induced diabetic animals and various in vitro tests have been used
      to reveal the prothrombotic state of diabetic patients. However, the results are
      not consistent. In the present study, platelet reactivity of spontaneously
      diabetic Goto-Kakizaki rats in vivo and in vitro was evaluated by laser-induced
      and shear-induced thrombosis models, which are physiologically relevant to
      thrombosis. Both results showed platelet hyperreactivity.

PMID- 12189020
TI  - Interactions of platelets with Synthocytes, a novel platelet substitute.
AB  - A platelet substitute, Synthocytes, is being developed for the prevention and
      treatment of thrombocytopenia. Synthocytes are composed of fibrinogen adsorbed on
      heat stabilised albumin microcapsules of defined size. The purpose of this study
      was to perform experiments in vitro to investigate the capacity of Synthocytes to
      interact with platelets, one of the means through which Synthocytes may
      contribute to haemostatic plug formation in vivo. Synthocytes were found to
      interact with platelets as shown by platelet aggregation assays and measurements
      of [(14)C]5HT release from platelets in whole blood and platelet-rich plasma.
      Platelet-Synthocytes co-aggregate formation was demonstrated directly using flow
      cytometry and the presence of activated platelets in these co-aggregates was
      demonstrated using an antibody to P-selectin. Synthocytes enhanced platelet
      responsiveness to conventional aggregating agents such as ADP. Indeed,
      antagonists of the action of ADP on platelets inhibited the direct effects of
      Synthocytes on platelets in whole blood, as did a GPIIb/IIIa antagonist.
      Enhancement of annexin V binding was also observed, indicative of increased pro
      coagulant activity. Experiments performed with control microcapsules (lacking
      fibrinogen) confirmed the importance of fibrinogen in the interactions that
      occurred. The results suggest that fibrinogen on the surface of Synthocytes can
      interact with GPIIb/IIIa on platelets to induce platelet activation, secretory
      activity and aggregation, and that ADP contributes to this process. This initial
      interaction renders platelets more susceptible to the stimulatory effects of
      other platelet-activating agents. It is considered likely that in the clinical
      setting of thrombocytopenia any interaction between Synthocytes and residual
      platelets that are present may contribute to primary haemostasis.

PMID- 12189022
TI  - Platelet aggregation and intracellular calcium mobilisation responses are
      enhanced by cyclosporin A but not by pimecrolimus (SDZ ASM 981).
AB  - It has been shown previously that cyclosporin A enhances platelet aggregation
      responses, particularly to adenosine diphosphate (ADP). In this investigation
      platelet responses to ADP in the presence of cyclosporin A and pimecrolimus (SDZ
      ASM 981), a new cell selective inhibitor of inflammatory cytokines, were
      determined. Measurements were performed in whole blood using a sensitive platelet
      counting method and in platelet-rich plasma (PRP) using a Biola laser
      aggregometer. The latter monitors both aggregate formation and aggregate size. In
      vitro studies were performed using recombinant hirudin as anticoagulant in order
      that physiological concentrations of divalent cation concentrations were
      maintained. Studies using both methods confirmed an enhanced aggregation response
      to ADP in the presence of cyclosporin A. In contrast, aggregation responses were
      not enhanced in the presence of pimecrolimus, either in PRP or in whole blood
      where a slight reduction of ADP-induced aggregation was seen at concentrations of
      pimecrolimus >10(-6) M. The effects of cyclosporin A and pimecrolimus on ADP
      induced calcium mobilisation in platelets were determined using a flow cytometric
      method. A significant increase in intracellular calcium mobilisation was seen in
      the presence of cyclosporin A but not in the presence of pimecrolimus. Enhanced
      platelet aggregation responses to ADP observed in the presence of cyclosporin A
      may be a consequence of enhanced ADP-induced calcium mobilisation.

PMID- 12189021
TI  - Effect of paraformaldehyde on platelet size and on measurement of surface IgG.
AB  - In many platelet assays, as in measurement of platelet-adherent IgG (PAIgG),
      platelets are fixed in paraformaldehyde (PFA). To better clarify the effect of
      PFA on platelet size and on PAIgG measurement we compared PAIgG levels in a
      series of 40 samples, with or without PFA fixing. We used an ELISA which was set
      up on unfixed platelets and gave excellent results in terms of linearity (r =
      0.923), precision (mean CV = 5%) and correlation with a platelet suspension
      immunofluorescence test. We found PAIgG values in unfixed platelets were about 10
      fold higher than in PFA-fixed (0.411 +/- 0.172 fg/platelet vs. 0.035 +/- 0.019
      fg/platelet). This discrepancy could be a consequence of the smaller mean
      platelet volume (MPV) of washed platelets when fixed in PFA (8.0 +/- 0.8 fl as
      compared to 10.1 +/- 1.07). This effect of PFA could decrease the amount of
      binding sites for IgG exposed on the platelet membrane and hence explain the
      significantly lower PAIgG values observed in fixed platelets. The PAIgG
      measurements on unfixed platelets from 200 healthy subjects displayed a Gaussian
      distribution with a mean +/- SD of 0.32 +/- 0.13 fg/platelet, i.e., 1200 +/- 500
      molecules/platelet.

PMID- 12189023
TI  - The virucidal effect of platelet concentrates: preliminary study and first
      conclusions.
AB  - Despite the increased safety of blood components, achieved through improved donor
      selection and testing, transfusion recipients remain at risk of transfusion
      associated diseases. Transfusion of cellular blood components has been implicated
      in transmission of viral, bacterial and protozoan diseases. Investigators have
      studied a myriad of processes for pathogen depletion and/or inactivation. No
      successful treatments, apart the leukodepletion, have already been identified for
      red cells and platelets. And more, several evidences indicate that platelets play
      a key role in host defence against infection. High levels of pathogens were added
      to single-donor platelet concentrates (PC) containing 3 to 5 10(11) platelets in
      300 ml. The infectivity of each pathogen was measured with established biologic
      assays. The following levels of pathogen inactivation were achieved : >10(2.63)
      plaque-forming units (PFU) per ml of adenovirus 5 (ADV5), >10(5.6) PFU per ml of
      Poliovirus 1 (P1) and >10(4.1) PFU per ml of vaccinia virus (VaV). In conclusion,
      the PC show a potential virucidal effect. This inactivation process has been
      found with bacteria and still remains unknown for viruses.

PMID- 12189024
TI  - Flow cytometric assay of platelet glycoprotein receptor numbers in
      hypercholesterolemia.
AB  - In this study, platelet glycoprotein (Gp) receptor numbers were measured by a
      flow cytometric assay using Cytoquant Gp in seven hypercholesterolemic and five
      normal subjects. Thrombin receptor agonist peptide (TRAP) was used to activate
      platelets. In hypercholesterolemia the Gp receptor numbers per resting platelet
      were found to be: 38,629 +/- 8,538 (GpIIb/IIIa), 22,269 +/- 5,628 (GpIb), 37,037
      +/- 9,810 (GpIIIa), 224 +/- 504 (CD62-P). After activation, receptor numbers were
      determined to be: 56,399 +/- 9,003 (GpIIb/IIIa), 10,970 +/- 5,319 (GpIb), 50,715
      +/- 7,904 (GpIIIa), 1,222 +/- 687 (P-selectin). In the normal group before the
      activation, receptor numbers were: 43,828 +/- 8,862 (GpIIb/IIIa), 22,166 +/-
      3,847 (GpIb), 42,351 +/- 1,049 (GpIIIa), 62 +/- 139 (CD62-P), After activation,
      receptor numbers were determined to be: 60,573 +/- 4,294 (GpIIb/IIIa), 13,003 +/-
      4,118 (GpIb), 52, 067 +/- 1,039 (GpIIIa), 3,608 +/- 1,508 (CD62-P). In
      hypercholesterolemic subjects, GpIIb/IIIa and GpIIIa receptor numbers on
      activated platelets increased significantly, whereas P-selectin numbers remained
      unchanged. However, the GpIb levels decreased significantly. In the control
      group, after activation, GpIIb/IIIa and P-selectin receptors increased
      significantly, GpIIIa receptor numbers did not change significantly, whereas GpIb
      receptor numbers decreased significantly. When the GpIIb/IIIa, GpIb, GpIIIa
      receptor numbers of the control group and hypercholesterolemic group were
      compared before and after activation, no significant changes were observed (P >
      0.05). But P-selectin receptor numbers were significantly decreased in
      hypercholesterolemic patients compared to normals following TRAP activation (P <
      0.05). In this study, the effect of hypercholesterolemia on platelet function was
      observed. The striking observation about present study was the marked decrease in
      P-selectin expression after activation in the hypercholesterolemics compared to
      normals. This finding suggests some sort of platelet dysfunction in these
      individuals.

PMID- 12189025
TI  - Platelet activation during carotid endarterectomy and the antiplatelet effect of
      Dextran 40.
AB  - OBJECTIVE: To determine changes in platelet activation during carotid
      endarterectomy (CEA) and the antiplatelet effect of Dextran 40. METHODS:
      Prospective study in 40 patients undergoing CEA. Platelet activity was measured
      by whole blood flow cytometry and platelet aggregometry during CEA. The
      expression of P-selectin and the PAC-1 antigen were used as markers of platelet
      activation and aggregation. Patients received aspirin (75-300 mg) preoperatively
      and 5,000 units unfractionated heparin during surgery. High intensity transient
      signals (HITS) in the ipsilateral middle cerebral artery were monitored using
      transcranial Doppler (TCD) perioperatively. RESULTS: P-selectin expression
      increased after carotid clamping (P < 0.01) and clamp release (P < 0.05). There
      was higher expression of PAC-1 after carotid clamping (p < 0.05). Spontaneous and
      ADP-induced platelet aggregation increased after carotid clamping (P< 0.01) and
      release (P < 0.01). TCD monitoring showed an increased HITS count from
      preoperative levels, after clamp release (P < 0.01) and during recovery (P <
      0.01). After the operation, patients with more than 50 HITS per 30 min were
      started on an infusion of dextran 40 (n = 6). P-selectin expression decreased 24
      h after dextran 40 (P < 0.01). CONCLUSION: Significant platelet activation and
      aggregation occurs during CEA despite the current use of antiplatelet treatment.
      Dextran 40 had an antiplatelet effect after CEA providing further evidence that
      it may contribute to reducing thromboembolic complications.

PMID- 12189026
TI  - Characterization of [(3)H]idazoxan binding sites on human platelets.
AB  - Human platelets possess at least two non-adrenoceptor binding sites
      pharmacologically distinct from the alpha(2)-adrenoceptors. The effects of
      various imidazol(in)es on platelet aggregation have suggested that these
      compounds may interact with these non-adrenoceptor binding sites on platelets.
      [(3)H]Idazoxan is an antagonist of the alpha(2)-adrenoceptors frequently used to
      characterize imidazoline I(2) receptors. We evaluated the binding of
      [(3)H]idazoxan to human platelet membranes. In saturation experiments
      [(3)H]idazoxan (1.25-32 nM) recognized a single, saturable binding site with high
      affinity. However, competition assays revealed the presence of alpha(2A)
      adrenoceptors and a non-adrenoceptor minor population (25-39%) recognized with
      high affinity by the imidazoline drug with low affinity for alpha(2)
      adrenoceptors 2-BFI. After the addition of (-)adrenaline (5 microM) to mask
      alpha(2)-adrenoceptors, competition curves against [(3)H]idazoxan binding were
      biphasic. The imidazoline I(1) receptor-selective drugs, efaroxan and
      rilmenidine, recognized the minor component with high affinity, whereas the
      imidazoline I(2) receptor-selective drugs, guanabenz and 2-BFI, bound with high
      affinity to the major component. Further masking experiments in the presence of
      efaroxan (2 microM) or guanabenz (1 microM) confirmed that [(3)H]idazoxan labels
      two non-adrenoceptor binding sites pharmacologically compatible with imidazoline
      I(1) and I(2) receptors as well as alpha(2A)-adrenoceptors in human platelets.

PMID- 12189027
TI  - The presence and release of tissue factor from human platelets.
AB  - Tissue factor (TF) is a transmembrane receptor for FVII that triggers blood
      coagulation. It is not normally exposed to circulating blood, but may be produced
      by endothelium and monocytes under pathological conditions. Platelets take up TF
      positive microparticles from leukocytes and TF appears on platelets adhering to
      leukocytes following collagen stimulation of blood. However, the presence of TF
      in circulating platelets has not been directly demonstrated. In this study, flow
      cytometric analysis of washed platelets from five healthy adult volunteers
      demonstrated TF-antigen on both resting platelets and platelets activated by
      thrombin (0.1 U/ml), collagen (5 microg/ml) or ADP (5 microM). TF released by
      platelets was demonstrated in the supernatants of non-activated and activated
      washed platelets by dot-immunoblotting and Western blotting. The amount of TF
      released from non-activated and activated platelets was quantitated using an
      enzyme-linked immunosorbent assay (ELISA). Washed non-activated and platelets
      activated by thrombin, collagen or ADP released 27-35 pg TF per mg protein. TF
      associated with the platelet surface was biologically inactive, although released
      TF was functionally active as determined by a two-stage factor X activation
      assay. We conclude that platelets contain an inactive form of TF that may develop
      functional activity following its release. However, the role of platelet TF in
      health and disease remains to be determined.

PMID- 12189041
TI  - Advances in our understanding of peroxiredoxin, a multifunctional, mammalian
      redox protein.
AB  - Organisms living under aerobic conditions have developed various anti-oxidative
      mechanisms to protect them from damage by reactive oxygen species (ROS). A novel
      family of anti-oxidative proteins, designated as peroxiredoxin (Prx), has been
      identified in the past two decades and currently comprises six members in
      mammals. They share a common reactive Cys residue in the N-terminal region, and
      are capable of serving as a peroxidase and involve thioredoxin and/or glutathione
      as the electron donor. Prx1 to Prx4 have an additional Cys residue in the
      conserved C-terminal region, and are cross members as judged by the amino acid
      sequence similarity. Prx5 also contains an additional Cys in its C-terminal
      region which is less conserved. On the other hand, Prx6 has only one unique Cys.
      These Prx family members are distributed in the cytosol, mitochondria, peroxisome
      and plasma, all of which are potential sites of ROS production. In addition to
      their role as a peroxidase, however, a body of evidence has accumulated to
      suggest that individual members also serve divergent functions which are
      associated with various biological processes such as the detoxification of
      oxidants, cell proliferation, differentiation and gene expression. It would be
      expected that these functions might not necessarily depend on peroxidase activity
      and, therefore, it seems likely that the divergence is due to unique molecular
      characteristics intrinsic to each member. A comparative study of the divergence
      would lead to a better understanding of the biological significance of the Prx
      family.

PMID- 12189042
TI  - Chemical regulation of nitric oxide: a role for intracellular myoglobin?
AB  - The detailed chemistry of nitric oxide (*NO) and regulation of this potent signal
      molecule through interactions with cellular components are complex and not
      clearly understood. In the vasculature, *NO plays a crucial role in vessel
      dilation by activating soluble guanylyl cyclase (sGC) in vascular smooth muscle
      cells (VSMC). *NO is responsible for maintaining coronary blood flow and normal
      cardiac function. However, *NO is a highly reactive molecule and this reactivity
      toward a range of alternate substrates may interfere with the activation of its
      preferred molecular target within VSMC. Interestingly, marked changes to *NO
      homeostasis are linked to disease progression. Thus, the physiological
      concentration of *NO is carefully regulated. Myoglobin is a haem-containing
      protein that is present in relatively high concentration in cardiac and skeletal
      muscle. Recently, the presence of myoglobin has been confirmed in human smooth
      muscle. The role of intracellular myoglobin is generally accepted as that of a
      passive di-oxygen storage protein. However, oxygenated myoglobin readily reacts
      with *NO to yield higher order N-oxides such as nitrate, while both the ferrous
      and ferric forms of the protein form a stable complex with *NO. Together, these
      two reactions effectively eliminate *NO on the physiological time-scale and
      strongly support the idea that myoglobin plays a role in maintaining *NO
      homeostasis in tissues that contain the protein. Interestingly, human myoglobin
      contains a sulfhydryl group and forms an S-nitroso-adduct similar to haemoglobin.
      In this article we discuss the potential for human myoglobin to actively
      participate in the regulation of *NO by three distinct mechanisms, namely
      oxidation, ligand binding, and through formation of biologically active S-nitroso
      myoglobin.

PMID- 12189043
TI  - Antioxidant properties of a Tinospora cordifolia polysaccharide against iron
      mediated lipid damage and gamma-ray induced protein damage.
AB  - The antioxidant activity of an arabinogalactan polysaccharide (TSP) isolated from
      Tinospora cordifolia, an Indian medicinal plant, was studied. The polysaccharide
      showed good protection against iron-mediated lipid peroxidation of rat brain
      homogenate as revealed by the thiobarbituric acid reactive substances (TBARS) and
      lipid hydroperoxide (LOOH) assays. TSP also provided significant protection to
      protein against gamma-ray induced damage. The protective action can possibly be
      explained by its very high reactivity towards DPPH, superoxide radicals and the
      most damaging of radicals, the hydroxyl radical.

PMID- 12189044
TI  - Catecholamine effects on cardiac remodelling, oxidative stress and fibrosis in
      experimental heart failure.
AB  - The aim of the study was to assess the relationships between oxidative stress,
      cardiac remodelling and fibrosis on an experimental model of heart failure with
      adrenergic stimulation. Large myocardial infarction (approximately 50% of the
      left ventricle myocardium) was obtained by ligation of the left coronary artery
      of normotensive male Wistar rats. Sham animals were submitted to left thoracotomy
      without coronary ligation. In order to perform cardiac stimulation by
      catecholamines, mini-osmotic pumps were implanted in animals 10 weeks after
      surgery to deliver noradrenalin for a 2-week period. At the end of this period,
      the following investigations were performed: haemodynamics, morphometry, fibrosis
      quantification, plasma and tissue catecholamine assay and oxidative stress
      status. Coronary ligation induced dilatation of left ventricle with compensatory
      hypertrophy of the right ventricle and of the remaining left ventricle
      myocardium. This remodelling process was associated in non-infarcted myocardium
      with increased collagen infiltration and increased oxidative stress. Ten weeks
      after surgery, the chronic administration of noradrenalin for 2 weeks did not
      increase oxidative stress. Noradrenalin, however, induced inotropic stimulation
      and myocardial hypertrophy, but to a lesser extent in infarcted rats compared to
      sham rats. Our results suggest that noradrenalin infusion to levels in excess of
      those seen post-infarction is associated with fibrosis and oxidative stress.
      Moreover, noradrenalin in infarcted animals caused additional fibrosis without
      further increasing oxidative stress. The mechanism of catecholamine-induced
      fibrosis may thus involve different processes such as ischaemia, increased
      mechanical stress, cytokines and neurohormones.

PMID- 12189045
TI  - Hydroxyl radical scavenging action of capsaicin.
AB  - We recently reported that capsaicin (CAP) is capable of scavenging peroxyl
      radicals derived from 2,2'-azobis(2,4-dimethylvaleronitrile) as measured by
      electron spin resonance (ESR) spectroscopy. The present study describes the
      hydroxyl radical (HO*) scavenging ability of CAP as measured by DNA strand
      scission assay and by an ESR spin trapping technique with 5,5-dimethyl-1
      pyrroline-N-oxide (DMPO). The Fenton reaction [Fe(II)+ H(2)O(2) --> Fe(III) + HO*
      + HO(-)] was used as a source of HO*. The incubation of DNA with a mixture of
      FeSO(4) and H(2)O(2) caused DNA strand scission. The addition of CAP to the
      incubation mixture decreased the strand scission in a concentration-dependent
      manner. To understand the antioxidative mechanism of CAP, we used an ESR spin
      trapping technique. Kinetic competition studies using different concentrations of
      DMPO indicated that the decrease of the oxidative DNA damage was mainly due to
      the scavenging of HO* by CAP, not to the inhibition of the HO* generation system
      itself. We estimated the second order rate constants in the reaction of CAP and
      common HO* scavengers with HO* by kinetic competition studies. By comparison with
      the common HO* scavengers, CAP was found to scavenge HO* more effectively than
      mannitol, deoxyribose and ethanol, and to be equivalent to DMSO and benzoic acid,
      demonstrating that CAP is a potent HO* scavenger. The results suggest that CAP
      may act as an effective HO* scavenger as well as a peroxyl radical scavenger in
      biological systems.

PMID- 12189046
TI  - Response to oxidative stress as a welfare parameter in swine.
AB  - In pigs, the genetic selection for lean, large muscle blocks and fast growth has
      been linked to an increased prevalence of metabolic diseases such as porcine
      stress syndrome and mulberry heart disease. These diseases are associated with
      cardiovascular inadequacy, which may lead to oxidative stress. In the present
      study, reactive oxygen metabolites (ROMs) and the anti-oxidant power (OXY) in
      sera of different swine groups were investigated. The following groups were
      selected (each around 80 kg body weight): wild boars (WB), Cinta Senese (CS), and
      Landrace x Large White (LxLW), the latter as both specific pathogen-free (SPF)
      and intensively farmed animals. In addition, a group of LxLW agonic sows (AS) was
      also investigated; this group is known to be under oxidative stress. Two
      colorimetric micro-methods were used to measure ROMs and OXY; ROMs were expressed
      as mM H(2)O(2) and OXY as microM HOCl neutralised. Between groups, average ROM
      and OXY values were found to be significantly different by one-way ANOVA (P <
      0.001). ROM levels were lower in WB (13.41 +/- 1.85) and CS (19.27 +/- 1.68), and
      highest in LxLW (42.00 +/- 1.36). OXY values ranged from 260.10 +/- 22.13 (WB) to
      396.90 +/- 9.83 (LxLW). Only one swine group (the CS group) showed a significant,
      positive correlation between ROM and OXY values. The AS group even showed a
      negative correlation between ROM and OXY values. These results imply satisfactory
      environmental coping occurred only within the CS group. Results are discussed in
      the light of animal welfare legislation, food safety and consumers' protection.

PMID- 12189047
TI  - Surgical stress during operation for gastrointestinal cancer increases plasma
      thioredoxin levels and decreases mitochondrial membrane potential in peripheral
      blood lymphocytes.
AB  - Surgical stress is difficult to evaluate quantitatively. It has been reported
      that mitochondrial membrane potential (delta psi(m)) in the peripheral blood
      lymphocytes (PBLs) is decreased by surgical stress. Thioredoxin (TRX), a small
      protein with redox-active dithiol/disulfide in the active site, is induced by a
      variety of oxidative stresses and secreted from the cells. Accumulating evidence
      shows that plasma levels of TRX are elevated in oxidative stress-associated
      disorders. In the present study, we examined plasma levels of TRX in cases
      undergoing operations for gastrointestinal cancer. Plasma levels of TRX were
      significantly elevated on the first postoperative day compared with the pre
      operative levels. The changes in the plasma TRX levels tended to show an inverse
      relationship with the changes in delta psi(m) in PBLs, which shows a significant
      decrease caused by surgical stress. Plasma TRX levels as well as delta psi(m) in
      PBLs are valuable markers to evaluate surgical stress.

PMID- 12189048
TI  - Protective effects of green tea polyphenols and their major component, (-)
      epigallocatechin-3-gallate (EGCG), on 6-hydroxydopamine-induced apoptosis in PC12
      cells.
AB  - Green tea polyphenols exert a wide range of biochemical and pharmacological
      effects, and have been shown to possess antimutagenic and anticarcinogenic
      properties. Oxidative stress is involved in the pathogenesis of Parkinson's
      disease. However, although green tea polyphenols may be expected to inhibit the
      progression of Parkinson's disease on the basis of their known antioxidant
      activity, this has not previously been established. In the present study, we
      evaluated the neuroprotective effects of green tea polyphenols in the Parkinson's
      disease pathological cell model. The results show that the natural antioxidants
      have significant inhibitory effects against apoptosis induced by oxidative
      stress. 6-Hydroxydopamine (6-OHDA)-induced apoptosis in catecholaminergic PC12
      cells was chosen as the in vitro model of Parkinson's disease in our study.
      Apoptotic characteristics of PC12 cells were assessed by MTT assay, flow
      cytometry, fluorescence microscopy and DNA fragmentation. Green tea polyphenols
      and their major component, EGCG at a concentration of 200 microM, exert
      significant protective effects against 6-OHDA-induced PC12 cell apoptosis. EGCG
      is more effective than the mixture of green tea polyphenols. The antioxidant
      function of green tea polyphenols may account for this neuroprotective effect.
      The present study supports the notion that green tea polyphenols have the
      potential to be effective as neuropreventive agents for the treatment of
      neurodegenerative diseases.

PMID- 12189049
TI  - Similarity in the distribution of F(2)-isoprostanes in the lipid subfractions of
      atherosclerotic plaque and in vitro oxidised low density lipoprotein.
AB  - Oxidation of low density lipoprotein (LDL) in vivo is thought to play a critical
      role in the initiation of atherosclerosis. F(2)-isoprostanes are compounds
      resulting from non-enzymatic oxidation of arachidonic acid and elevated levels
      are present in human atherosclerotic plaque. However, little is known about the
      formation of F(2)-isoprostanes in plaque lesions or their distribution in lipid
      subclasses. Given that LDL and tissue lipid subfractions (such as phospholipids,
      cholesterol esters and triglycerides) all contain significant levels of
      arachidonic acid, the aim of this study was to examine the relative distribution
      of F(2)-isoprostanes in the different lipid fractions of LDL oxidised in vitro,
      and compare this to the distribution in atherosclerotic plaque. The results
      reveal that while the majority of F(2)-isoprostanes are present in the
      phospholipid or surface lipid fractions, the core lipids (cholesterol
      esters/triglycerides) contribute at least 10% of the total F(2)-isoprostanes in
      both LDL oxidised in vitro and human atherosclerotic plaque. The remarkably
      similar profiles between the oxidised LDL and advanced atherosclerotic plaque
      suggests oxidation in vivo, is predominantly via non-enzymatic processes directed
      towards the surface lipids.

PMID- 12189050
TI  - Our Lilliputian scientific lexicon.

PMID- 12189051
TI  - Xanthine oxidase is a peroxynitrite synthase: newly identified roles for a very
      old enzyme.

PMID- 12189052
TI  - Biological regulation through protein disulfide bond cleavage.
AB  - It is thought that disulfide bonds in secreted proteins are inert because of the
      oxidizing nature of the extracellular milieu. We have suggested that this is not
      necessarily the case and that certain secreted proteins contain one or more
      disulfide bonds that can be cleaved and that this cleavage is central to the
      protein's function. This review discusses disulfide bond cleavage in the secreted
      soluble protein, plasmin. Cleavage of plasmin disulfide bond(s) triggers peptide
      bond cleavage and formation of the tumour angiogenesis inhibitor, angiostatin.
      Tumour cells secrete phosphoglycerate kinase which facilitates cleavage of the
      plasmin disulfide bond(s). Phosphoglycerate kinase is not a conventional
      disulfide bond reductase. We propose that phosphoglycerate kinase facilitates
      cleavage of a particular plasmin disulfide bond by hydroxide ion, which results
      in formation of a sulfenic acid and a free thiol. The free thiol is then
      available to exchange with another nearby disulfide bond resulting in formation
      of a new disulfide and a new free thiol. The reduced plasmin is then susceptible
      to discreet proteolysis which results in release of angiostatin.

PMID- 12189053
TI  - Yeast thioredoxin peroxidase expression enhances the resistance of Escherichia
      coli to oxidative stress induced by singlet oxygen.
AB  - Singlet oxygen ((1)O(2)) is a highly reactive form of molecular oxygen that may
      harm living systems by oxidizing critical cellular macromolecules. A soluble
      protein from Saccharomyces cerevisiae specifically provides protection against a
      thiol-containing metal-catalyzed oxidation system (thiol/Fe(3+)/O(2)) but not
      against an oxidation system without thiol. This 25 kDa protein acts as a
      peroxidase but requires the NADPH-dependent thioredoxin system or a thiol
      containing intermediate, and was named thioredoxin peroxidase (TPx). The role of
      TPx in the cellular defense against oxidative stress induced by singlet oxygen
      was investigated in Escherichia coli containing an expression vector with a yeast
      genomic DNA fragment that encodes TPx and mutant in which the catalytically
      essential amino acid cysteine (Cys-47) has been replaced with alanine by a site
      directed mutagenesis. Upon exposure to methylene blue and visible light, which
      generates singlet oxygen, there was a distinct difference between the two strains
      in regard to growth kinetics, viability, the accumulation of oxidized proteins
      and lipids, and modulation of activities of superoxide dismutase and catalase.
      The results suggest that TPx may play an important protective role in a singlet
      oxygen-mediated cellular damage.

PMID- 12189054
TI  - Oxygen consumption and electron spin resonance studies of free radical production
      by alveolar cells exposed to anoxia: inhibiting effects of the antibiotic
      ceftazidime.
AB  - By EPR spectroscopy, we investigated free radical production by cultured human
      alveolar cells subjected to anoxia/re-oxygenation (A/R), and tested the effects
      of ceftazidime, an antibiotic previously demonstrated to possess antioxidant
      properties. Two A/R models were performed on type II pneumocytes (A549 cell
      line), either on cells attached to culture dishes (monolayer A/R model; 3.5 h of
      anoxia, 30 min of re-oxygenation) or after cell detachment (suspension A/R model;
      1 h of anoxia, 10 min of re-oxygenation). Ceftazidime and selective inhibitors
      (SOD, Tiron, L-NMMA) were added before anoxia. Free radical production was
      assessed by the EPR spin trapping technique. Oxygen consumption was monitored, in
      parallel with EPR studies, in the suspension A/R model. The production of free
      radical species was demonstrated by the generation of PBN-radical adducts: (a(N)
      = 15.2 G) in the monolayer A/R model and a six-line EPR spectrum (a(N) = 15.7 G
      and a(H) = 2.7 G) in the suspension A/R model. A kinetic study performed by
      oximetry, in parallel with EPR spectroscopy, demonstrated marked alterations of
      the cell respiratory function and that the free radical production started during
      anoxia and increased during re-oxygenation. In the suspension A/R model, the
      amplitude of EPR spectra were decreased upon the addition of 200 U/ml SOD (37%
      inhibition), 0.1 mM Tiron (67% inhibition) and 1 mM L-NMMA (43% inhibition).
      Addition of 1 mM ceftazidime decreased the amplitude of EPR spectra (37%
      inhibition) in both A/R models. Complementary in vitro EPR studies demonstrated
      that CAZ scavenged the hydroxyl radical (produced by the Fenton reaction). The
      protective effect of ceftazidime in the cell model could thus be linked to its
      ability to scavenge superoxide anions, nitrogen-derived species and hydroxyl
      radicals.

PMID- 12189055
TI  - Protective properties of butanolic extract of the Calendula officinalis L.
      (marigold) against lipid peroxidation of rat liver microsomes and action as free
      radical scavenger.
AB  - Calendula officinalis (marigold) has many pharmacological properties. It is used
      for the treatment of skin disorders, pain and also as a bactericide, antiseptic
      and anti-inflammatory. Reactive oxygen species (ROS) and reactive nitrogen
      species (RNS) are known to participate in the pathogenesis of various human
      diseases and may be involved in the conditions which C. officinalis is used to
      treat. The aim of this study was to investigate the relationship between the
      beneficial properties of this plant and its antioxidant action. The butanolic
      fraction (BF) was studied because it is non-cytotoxic and is rich in a variety of
      bioactive metabolites including flavonoids and terpenoids. Superoxide radicals
      (O(2)(*-)) and hydroxyl radicals (HO(*)) are observed in decreasing
      concentrations in the presence of increasing concentrations of BF with IC(50)
      values of 1.0 +/- 0.09 mg/ml and 0.5 +/- 0.02 mg/ml, respectively, suggesting a
      possible free radical scavenging effect. Lipid peroxidation in liver microsomes
      induced by Fe(2+)/ascorbate was 100% inhibited by 0.5 mg/ml of BF (IC(50) = 0.15
      mg/ml). Its total reactive antioxidant potential (TRAP) (in microM Trolox
      equivalents) was 368.14 +/- 23.03 and its total antioxidant reactivity (TAR) was
      calculated to be 249.19 +/- 14.5 microM. The results obtained suggest that the
      butanolic fraction of C. officinalis possesses a significant free radical
      scavenging and antioxidant activity and that the proposed therapeutic efficacy of
      this plant could be due, in part, to these properties.

PMID- 12189056
TI  - On-line antioxidant activity determination: comparison of hydrophilic and
      lipophilic antioxidant activity using the ABTS*+ assay.
AB  - The ABTS/H(2)O(2)/HRP decoloration method is capable of determining both
      hydrophilic (in buffered media) and lipophilic (in organic media) antioxidant
      properties in complex samples. Now, we have adapted this method for on-line
      chromatographic determination. The easy, rapid and controlled generation of the
      ABTS radical and its great stability in buffered and organic media were important
      characteristics in the measurement of antioxidant activities. The HPLC-ABTS
      method used two pumps (one for isocratic eluting-phase and the other for
      preformed ABTS radical) and an UV-VIS diode array detector. The dual analysis of
      samples -- conventional (with UV-VIS detection) and ABTS-scavenging (at 600 nm) -
      provided valuable on-line information about the correspondence between the
      presence of a determined compound and its possible antioxidant activity, and was
      applicable to both hydrophilic and lipophilic antioxidants (HAA and LAA). A
      comparison between HAA and LAA determined by the end-point method and by the on
      line HPLC method is presented. The application to juices showed that both methods
      are suitable, sensitive and selective, gave similar values, and the HPLC-ABTS
      method contributed additional information about the antioxidant activity profile.

PMID- 12189057
TI  - Low-density lipoprotein modification by normal, myeloperoxidase-deficient and
      NADPH oxidase-deficient granulocytes and the impact of redox active transition
      metal ions.
AB  - The modification of low-density lipoprotein (LDL) by normal, myeloperoxidase
      (MPO)-deficient and NADPH oxidase-deficient granulocytes was investigated using
      the monoclonal antibody (mAb) OB/04, which was originally generated against
      copper-oxidized LDL. Incubation of LDL with normal granulocytes increased the
      reactivity of LDL with mAb OB/04. These effects were even more pronounced using
      MPO-deficient granulocytes. Inhibitors of oxidative reactions (the NADPH oxidase
      inhibitor diphenyleneiodonium chloride [DPI], catalase, superoxide dismutase
      [SOD]) did not significantly reduce LDL oxidation by normal granulocytes.
      Furthermore, granulocytes of a patient with NADPH oxidase deficiency were almost
      equally effective as normal granulocytes, indicating that oxidative burst-derived
      reactive oxygen species are of only minor importance in the generation of mAb
      OB/04-detectable new epitopes on LDL in vitro. In contrast, incubation of LDL
      with iron and copper prior to and during incubation with normal granulocytes
      markedly enhanced the generation of OB/04-detectable epitopes. It is supposed
      that, besides superoxide (in normal and MPO-deficient granulocytes) or instead of
      superoxide (in NADPH oxidase-deficient granulocytes), lytic enzymes released by
      activated granulocytes may enhance the availability of transition metals for
      oxidation of LDL. Our results support the concept that transition-metal-dependent
      pathways of LDL oxidation in combination with degranulation products of
      granulocytes are important.

PMID- 12189058
TI  - Bioethics for the president and bioethics for the people.

PMID- 12189059
TI  - What makes placebo-controlled trials unethical?
AB  - The leading ethical position on placebo-controlled clinical trials is that
      whenever proven effective treatment exists for a given condition, it is unethical
      to test a new treatment for that condition against placebo. Invoking the
      principle of clinical equipoise, opponents of placebo-controlled trials in the
      face of proven effective treatment argue that they (1) violate the therapeutic
      obligation of physicians to offer optimal medical care and (2) lack both
      scientific and clinical merit. We contend that both of these arguments are
      mistaken. Clinical equipoise provides erroneous ethical guidance in the case of
      placebo-controlled trials, because it ignores the ethically relevant distinction
      between clinical trials and treatment in the context of clinical medicine and the
      methodological limitations of active-controlled trials. Placebo controls are
      ethically justifiable when they are supported by sound methodological
      considerations and their use does not expose research participants to excessive
      risks of harm.

PMID- 12189060
TI  - When argument fails.

PMID- 12189061
TI  - Subject indifference and the justification of placebo-controlled trials.

PMID- 12189062
TI  - Avoiding a Jekyll-and-Hyde approach to the ethics of clinical research and
      practice.

PMID- 12189063
TI  - Are concerns about the ethics of placebos a stalking horse for other issues?

PMID- 12189064
TI  - Exploiting subjects in placebo-controlled trials.

PMID- 12189065
TI  - Therapeutic beneficence and placebo controls.

PMID- 12189067
TI  - Failure to conduct a placebo-controlled trial may be unethical.

PMID- 12189066
TI  - Clarifying the ethics of clinical research: a path toward avoiding the
      therapeutic misconception.

PMID- 12189068
TI  - Effective trial design need not conflict with good patient care.

PMID- 12189070
TI  - Exploitation and the ethics of clinical trials.

PMID- 12189069
TI  - Clinical research should not be permitted to escape the ethical orbit of clinical
      care.

PMID- 12189071
TI  - I thought we were in this together?

PMID- 12189072
TI  - Distinguishing dilemmas in the ethics of placebo-controlled trials.

PMID- 12189073
TI  - Placebo controls: scientific and ethical issues.

PMID- 12189074
TI  - Therapeutic beneficence and patient recruitment in randomized controlled clinical
      trials.

PMID- 12189075
TI  - Cynthia's dilemma: consenting to heroin prescription.
AB  - Heroin prescription involves the medical provision of heroin in the treatment of
      heroin addiction. Rudimentary clinical trials on that treatment modality have
      been carried out and others are currently underway or in development. However, it
      is questionable whether subjects considered for such trials are mentally
      competent to consent to them. The problem has not been sufficiently appreciated
      in ethical and clinical discussions of the topic. The challenges involved throw
      new light on the role of value and accountability in contemporary discussions of
      mental competence.

PMID- 12189076
TI  - Who holds the leash?

PMID- 12189077
TI  - Unsafe presumptions in clinical research.

PMID- 12189078
TI  - Resisting the temptations of addiction rhetoric.

PMID- 12189079
TI  - Ethics and heroin prescription: no more fuzzy goals!

PMID- 12189080
TI  - Cynthia's Dilemma.

PMID- 12189081
TI  - A "fix" of reality.

PMID- 12189082
TI  - Addiction and consent.

PMID- 12189083
TI  - Choice, rationality, and substance dependence.

PMID- 12189084
TI  - Authenticity and the hijacked brain.

PMID- 12189102
TI  - Towards an international standard on occupational health and safety management.
AB  - As a result of the need for companies to manage occupational health and safety,
      as well as the absence of a globally accepted international standard, numerous
      organisations have developed their own models in the shape of guides, standards,
      or guidelines. However, the resultant dispersion is creating confusion among
      companies, rather than making life easier for them. In this article, we look at
      the current situation as far as available European management systems are
      concerned, and the emergent trends in the development of an international
      standard. Moreover, we present the special case of Spain, whose broad legislation
      on occupational health and safety might hinder the adoption of an international
      model by Spanish companies.

PMID- 12189085
TI  - Ethical evaluation of heroin-prescription research: an insider's view.

PMID- 12189103
TI  - A job safety program for construction workers designed to reduce the potential
      for occupational injury using tool box training sessions and computer-assisted
      biofeedback stress management techniques.
AB  - This project was conducted with a multicultural construction company in Hawaii,
      USA. The job duties performed included drywall and carpentry work. The following
      objectives were selected for this project: (a) fire prevention training and
      inspection of first aid equipment; (b) blood-borne pathogen training and risk
      evaluation; (c) ergonomic and risk evaluation intervention program; (d)
      electrical safety training and inspection program; (e) slips, trips, and falls
      safety training; (f) stress assessment and Personal Profile System; (g) safety
      and health program survey; (h) improving employee relations and morale by
      emphasizing spirituality; and (i) computer-assisted biofeedback stress management
      training. Results of the project indicated that observed safety hazards, reported
      injuries, and levels of perceived stress. were reduced for the majority of the
      population.

PMID- 12189104
TI  - Intranet-based safety documentation in management of major hazards and
      occupational health and safety.
AB  - In the European Union, Council Directive 96/82/EC requires operators producing,
      using, or handling significant amounts of dangerous substances to improve their
      safety management systems in order to better manage the major accident potentials
      deriving from human error. A new safety management system for the Viikinmaki
      wastewater treatment plant in Helsinki, Finland, was implemented in this study.
      The system was designed to comply with both the new safety liabilities and the
      requirements of OHSAS 18001 (British Standards Institute, 1999). During the
      implementation phase experiences were gathered from the development processes in
      this small organisation. The complete documentation was placed in the intranet of
      the plant. Hyperlinks between documents were created to ensure convenience of
      use. Documentation was made accessible for all workers from every workstation.

PMID- 12189105
TI  - Human performance cognitive-behavioral modeling: a benefit for occupational
      safety.
AB  - Human Performance Modeling (HPM) is a computer-aided job analysis software
      methodology used to generate predictions of complex human-automation integration
      and system flow patterns with the goal of improving operator and system safety.
      The use of HPM tools has recently been increasing due to reductions in
      computational cost, augmentations in the tools' fidelity, and usefulness in the
      generated output. An examination of an Air Man-machine Integration Design and
      Analysis System (Air MIDAS) model evaluating complex human-automation integration
      currently underway at NASA Ames Research Center will highlight the importance to
      occupational safety of considering both cognitive and physical aspects of
      performance when researching human error.

PMID- 12189106
TI  - Computer-intensive methods in traffic safety research.
AB  - The analysis of traffic safety data archives has improved markedly with the
      development of procedures that are heavily dependent upon computers. Three such
      procedures are described here. The first procedure involves using computers to
      assist in the identification and correction of invalid data. The second procedure
      makes greater computational demands, and involves using computerized algorithms
      to fill in the "gaps" that typically occur in archival data when information
      regarding key variables is not available. The third and most computer-intensive
      procedure involves using data mining techniques to search archives for
      interesting and important relationships between variables. These procedures are
      illustrated using examples from data archives that describe the characteristics
      of traffic accidents in the USA and Australia.

PMID- 12189107
TI  - Factor analysis of safety for visitors to a mega-event.
AB  - This paper investigated the safety factors considered by visitors to the Kwangju
      Biennale 2000 and analyzed the correlation between the safety factors and the
      demographic characteristics of the visitors. Global tourism increased throughout
      the 1990s, with the biggest surge occurring in the Asia-Pacific region. Long
      distance travel is also increasing, and at a rate faster than the global average.
      The opportunities for event tourism appear to be strong almost everywhere, even
      though recessions may have an impact on these destinations. Along with this
      upward trend, competition for more desirable tourists is also surging (Getz,
      1997). Therefore event tourism is appearing as a powerful method in the fierce
      competition around the tourism industry.

PMID- 12189108
TI  - Prevention of falls on the level in occupational situations: a major issue, a
      risk to be managed.
AB  - The terminology used to designate falls on the level is broadly based and the
      accidents concerned are only very rarely defined explicitly. A definition of
      falls on the level in occupational situations is therefore proposed. We attempt
      to define the issue represented by the prevention of such accidents on the basis
      of statistical data, prior to explaining the twin objectives focused on in the
      field of their prevention. We then propose a summary of unbalance risk factors in
      occupational situations. These factors are associated with different components
      of the occupational situation they concern: individuals, their tasks, the
      equipment used, or the working environment. The diversity of accident contexts
      and different in-company prevention possibilities are thereby highlighted.
      Finally, we discuss a number of consequences in prevention terms.

PMID- 12189109
TI  - A systematic procedure for modeling usability based on product design variables:
      a case study in audiovisual consumer electronic products.
AB  - A systematic modeling approach to describing, prescribing, and predicting
      usability of a product has been presented. Given the evaluation results of the
      usability dimension (UD) and the measurement of the product's design variables,
      referred to as the human interface elements (HIEs), the approach enables one to
      systematically assess the relationship between the UD and HIEs. The assessed
      relationship is called a usability model. Once built, such a usability model can
      relate, in a quantitative manner, the HIEs directly to the UDs, and thus can
      serve as an effective aid to designers by evaluating and predicting the usability
      of an existing or hypothetical product. A usability model for elegance of
      audiovisual consumer electronic products has been demonstrated.

PMID- 12189110
TI  - Study on changes of heme oxygenase expression in patients with chronic
      obstructive pulmonary disease.
AB  - OBJECTIVE: To investigate the changes of heme oxygenase(HO) expression in
      patients with chronic obstructive pulmonary disease(COPD). METHODS: The patients
      were divided into 3 groups: COPD(group 1,n = 36),COPD complicated by lung
      cancer(group 2, n = 28) and lung cancer group(group 3,n = 22). A total of 125
      healthy individuals(group 4) served as control. Blood gas was analyzed and
      pulmonary function was assayed in all groups. The levels of carbon monoxide
      hemoglobin (COHb) in arterial blood of 4 groups and HO-1 activity of lung tissues
      resected due to lung cancer in group 2 and group 3 were tested with ultraviolet
      spectrop hotometry. The levels of HOmRNA and protein expressions of lung tissues
      in group 2,group 3 and some of group 4(the lung tissues were obtained from
      traffic accident operations) were measured by reverse transcription-polymerase
      chain reaction and by immunohistochemistry. RESULTS: Partial pressure of oxygen
      in arterial blood fell obviously to lower than 8kPa in group 1 and group 2, but
      the pH values, partial pressures of carbon dioxide in arterial, blood and HCO(3)
      were in normal ranges. Diffusion capacity for carbon monoxide of the
      lung(D(L)CO,69.521 +/- 13.979), D(L)CO/alveolar ventilation(V(A),66.091 +/-
      16.423), and forced expiratory volume in one second (FEV(1)) in predata
      (FEV(1)%/Pred, 52.408 +/- 10.635) in group 1 and D(L)CO (71.323 +/- 11.254),
      D(L)CO/V(A)(68.152 +/- 18.326), and FEV(1)%/Pred (53.897 +/- 9.467) in group 2
      were significantly lower than those in group 3 and group 4. The ratio of residual
      volume(RV) to total lung capacity(TLC) was significantly higher in group 1(50.309
      +/- 4.368) and group 2(49.250 +/- 4.978) than those in other groups. The levels
      of COHb were significantly increased in the patients of group 1[(5.63 +/- 1.07)%]
      and group 2[(5.86 +/- 1.82)%] compared with those in group 3 [(1.65 +/- 0.56)%]
      and group 4 [(1.05 +/- 0.43) %, P < 0.01]. The bilirub in production was
      significantly increased in the group 2 [(492.25 +/- 117.32) pmol. mg protein (
      1). h (-1)] compared with those of group 3 [(289.32 +/-82.52) pmol. mg protein (
      1). h (-1)] and group 4 [(253.25 +/- 66.32) pmol. mg protein (-1). h (-1)].The
      levels of HO-1mRNA expression of lung tissues (the area without carcinomatous
      changes)(2.16 +/- 0.68) and that of pulmonary vessels(1.56 +/- 0.52)in group 2
      were significantly increased than those of other groups. The strong positive
      granules of HO-1 were observed in the cytoplasm of pulmonary alveolar wall,
      intrapulmonary vascular and bronchial wall in groups 2. CONCLUSION: The
      overexpression of HO may be a kind of compensatory regulation. Endogenous HO-CO
      system was involved in the regulation of COPD.

PMID- 12189111
TI  - The effect of losartan intervention on the regulation of pulmonary arterial
      collagen expression by protein kinase C in chronic hypoxic rat models.
AB  - OBJECTIVE: To investigate the regulating role of protein kinase C(PKC) and the
      effects of losartan intervention on the expression of pulmonary arterial collagen
      in chronic hypoxic rat models. METHODS: Thirty six rats were randomly divided
      into three groups: healthy control group(A), hypoxic model group(B),and hypoxic +
      losartan intervention group (C). MT% (vessel medial thichness/ total thichness)
      and WA% (vessel wall area/total area) of pulmonary arterioles were measured with
      light microscopy,the ultrastructures of pulmonary arterioles were observed by
      electronic microscope, the PKC activities of lung tissues were detected with
      radioactive method,the protein and(or) mRNA expression of PKC and collagen I, III
      in arterioles were observed using immunohistochemistry and in situ hybridization.
      The relative contents [integral light density(LD)] of PKC, collagen I, III and
      procollagen I, III mRNA in pulmonary arterioles were calculated with image
      analysor. RESULTS: (1) The mean pulmonary arterial pressure and weight ratio of
      right ventricle (RV) to left ventricle(LV)+septum( S)(RV/LV+S) in group B were
      significantly higher than those in group A(P < 0.01), but in group C they were
      significantly lower than those in group B (P < 0.01). (2) MT% and WA% of
      pulmonary arterioles in group B were significantly increased than those in group
      A (P < 0.01)   while in group C both the parameters were significantly decreased
      than those in group B (P < 0.01). Collagen fiber deposition in pulmonary
      arteriolar walls were inhibited in group C by electronic microscopy.(3) The
      total,cytoplasmic and cytomembrane PKC activities, as well as the ratio of
      cytomembrane PKC activity to total one in group B were significantly increased
      than those in group A(P < 0.01),while all these parameters in group C were
      significantly decreased than those of group B (P < 0.01). (4)LD of PKC,collagen I
      and procollagen I m RNA expressions in pulmonary arterioles were significantly
      increased in group B than those in group A(P < 0.01), but in group C they were
      significantly decreased than those in group B(P < 0.01). There were no
      significant differences in collagen III and procollagen IIImRNA expressions among
      the three groups(P > 0.05).(5)Significant positive correlations were found
      between the PKC activities and collagen I expressions(P < 0.05) and between the
      expressions of PKC and collagen I in pulmonary arterioles(P < 0.01). CONCLUSIONS:
      The PKC signal pathway participated the regulation of pulmonary arterial collagen
      expression in chronic hypoxic rat models and may play an important role in the
      pathogenesis of pulmonary hypertension and structural remodeling of pulmonary
      arterials. Losartan could reduce the hypoxic pulmonary hypertension by
      interference the role of PKC on pulmonary arterial collagen expression.

PMID- 12189112
TI  - Efficacy of domestic bisoprolol,enalapril and nifedipine retard in mild to
      moderate hypertension: a randomized double-blind multicenter clinical trial in
      China.
AB  - OBJECTIVE: To compare the efficacy and tolerability of bisoprolol, enalapril and
      nifedipine retard in the treatment of mild to moderate essential hypertension.
      METHODS: This is a randomized, double-blind, multicenter clinical trial. 331
      patients with mild to moderate hypertension in the army troop were randomly
      allocated to receive domestic bisoprolol (  n  =110,5 mg/d),enalapril (  n 
      =111,10 mg/d) and nifedipine retard (  n  =110,20 mg/day). Total duration of
      active drug treatment was 4 weeks. RESULTS: The total efficacy rates of domestic
      bisoprolol, enalapril and nifedipine retard were 80.0%, 82.0% and 81.8%
      respectively  P > 0.05  . The incidences of adverse events were 4.5%, 8.1% and
      19.1% (P < 0.01 ) in patients of bisoloprol, enalapril and nifedipine retard
      groups respectively. The adverse effects were mild in all the three groups.
      CONCLUSIONS: Domestic bisoprolol, enalapril and nifedipine retard are effective
      and well-tolerated in patients with mild to moderate essential hypertension. The
      occurrence of adverse effects were least in the bisoprolol group and most in the
      nifedipine retard group.

PMID- 12189113
TI  - Myocardial matrix metalloproteinase-3 and matrix metalloproteinase inhibitor-1
      expression in congestive heart failure.
AB  - OBJECTIVE: To study the changes of matrix metalloproteinase-3 (MMP-3) and tissue
      inhibitor of matrix metalloproteinase-1(TIMP-1) expression during congestive
      heart failure. METHODS: Using the reverse transcriptase-polymerase chain
      reaction(RT-PCR) assay, we detected MMP-3 and TIMP-1 expression in 31 patients
      with rheumatic heart disease (RHD) and 8 health subjects. Cardiac function
      parameters were measured with echocardiographs. RESULTS: Pathological changes of
      myocardial tissure in CHF with valvular heart disease showed typical myocardial
      remodeling. As compared with the control group, the contents of MMP-3 in RHD
      patients were increased significantly (  P < 0.01). The worse the cardiac
      function, the higher the contents of MMP-3. TIMP-1 expressions showed a reverse
      correlation. CONCLUSIONS: It is suggested that the altered expression of MMP-3
      and TIMP-1 contributes to myocardial remodeling and might lead to the development
      and progression of congestive heart failure. These changes may induce a direct
      effect on the progressive deterioration of cardiac function.

PMID- 12189114
TI  - The effect of sclerotherapy of bleeding esophageal variceal on survival of
      cirrhotic patients.
AB  - OBJECTIVE: To investigate the effect of various factors in sclerotherapy of
      cirrhotic esophageal variceal bleeding (CEVB) on the prognosis, model of survival
      was established. METHODS: Kaplan-Meier analysis was applied in patients with CEVB
      treated by sclerotherapy from April 1987 to June 2000 to evaluate the survival,
      with follow-up data of survival and 29 selected factors of prognosis. Risk
      factors were identified with Cox's Proportional Hazard Model. RESULTS: Cox's
      model shows that Child grading and outcome of varices are two factors that
      significantly influence the prognosis and survival. Survival of 1, 3 and 5 year
      for the entire group is 93.29%, 85.24% and 74.27%, respectively. Survival of 1
      year for patients of Child grade A, B and C is 98.88%, 95.97% and 82.32%,
      respectively, and survival of 5 year is 91.42%, 78.35% and 49.48%, respectively,
      with significant difference in survival curves. Outcome of esophageal varices is
      labeled with elimination, basically elimination, degree I, degree II and degree
      III, and survival of 1 year is 96.08%, 93.94%, 85.84%, 85.00% and 53.85%,
      respectively, survival of 5 year is 81.45%, 67.76%, 72.89%, 61.59% and 35.90%,
      respectively, with significant difference in survival curves. In patients of
      Child grade C with outcome of elimination or basically elimination, 1 year
      survival is 88.24%, and 2 year survival is 77. 98% approximately 83.63%. Survival
      curves of stratified groups are tended to converge after 50 months. CONCLUSIONS:
      Sclerotherapy for CEVB is an effective therapy to arrest emergent bleeding and
      prevent rebleeding. For patients of Child grade C,survival can also be prolonged,
      so it is advisable to take active measures. Repeat of sclerotherapy after about 4
      years may be necessary. Sclerotherapy can significantly prolong the survival.

PMID- 12189115
TI  - Small bowel bacterial overgrowth and endotoxemia in cirrhosis.
AB  - OBJECTIVE: To investigate the incidence of the small bowel bacterial overgrowth
      in cirrhotics and analyze the correlation among small bowel bacterial overgrowth
      (SBBO), plasma endotoxin level and plasma interleukin-2(IL-2), interleukin-6(IL
      6), or tumor necrosis factor alpha(TNF-alpha) level. METHODS: Small bowel
      bacterial overgrowth in 71 cirrhotics was test by glucose hydrogen breath test
      (GHBT); plasma endotoxin in cirrhotics was measured with limilus lysate test; and
      plasma cytokine (IL-2, IL-6 and TNF-alpha) was measured with a solid-phase enzyme
      linked immunosorbent assay; the incidence of SBBO in those 71 cirrhotics was
      investigated and the correlation between plasma endotoxin level and plasma IL-2,
      IL-6, or TNF-alpha level was analysed. RESULTS: (1)Positive GHBT were observed in
      18 of 71 icrrhotics(25.3%); (2) Plasma endotoxin, IL-2, IL-6 and TNF-alpha levels
      were significantly higher in those cirrhotic patients with positive GHBT than in
      those with negative GHBT [(0.715 +/- 0.229) Eu/L versus (0.379 +/- 0.223) Eu/L,
      (19.15 +/- 4.60) ng/L versus (9.41 +/- 6.69) ng/L, (93.29 +/- 27.37) ng/L versus
      (53.22 +/- 28.31) ng/L, (42.18 +/- 16.91) ng/L versus (27.72 +/- 17.06) ng/L,
      respectively; P < 0.01]; (3) A significant correlation was observed between the
      level of plasma endotoxin and the level of plasma IL-2(r = 0.894, P < 0.001), IL
      6(r  = 0.857,  P < 0.001) or TNF-alpha(  r  = 0.845,P < 0.001)in cirrhotics;
      CONCLUSIONS: (1)Plasma endotoxin, IL-2, IL-6,and TNF-alpha levels are increased
      in cirrhotic patients with SBBO, which suggests SBBO in cirrhotics may
      exasperated endotoxeamia;(2)Plasma endotoxin level in cirrhotics may stimulate
      some kinds of immune activated cells to produce IL-2, IL-6 and TNF-alpha, which
      may deteriorated cirrhosis or the complications.

PMID- 12189117
TI  - Large multifunctional proteasome 2 gene Arg60His variant in autoimmune thyroid
      disease in Shanghai Chinese.
AB  - OBJECTIVE: To investigate the relationship between Arg60His variant in the large
      multifunctional proteasome 2(LMP2) gene and autoimmunune thyroid disease (AITD)
      in Shanghai Chinese. METHODS: By means of PCR-restriction fragment length
      polymorphisms(RFLP) assay, the genotypes of Arg60His variant in the LMP2 gene
      were determined in 367 unrelated Shanghai Chinese, including 205 patients with
      AITD and 162 normal control individuals. The former group was further divided
      into two subgroups  78 subjects with positive thyrotrophin receptor
      antibody(TRAb) and 127 subjects with negative TRAb but positive either
      thyroglobulin antibody(TGAb),thyoid microsomal antibody(TMAb) or thyroid
      peroxidase antibody (TPOAb). RESULTS: Significant difference (  P = 0.000)of
      allele frequencies of R/H 60 in the LMP2 gene was observed between Shanghai
      Chinese (R 0.89,H 0.11) and white Caucasians (R 0.29, H 0.71)and was also
      observed between TRAb positive subgroup in AITD and normal controls. The
      frequencies of RH genotype and H allele in TRAb positive subgroup is
      significantly higher than those in normal controls(  P =
      0.037,0.047,respectively).In AITD group, the genotype and allele frequencies of
      Arg60His variant in the LMP2 gene showed no significant difference between other
      antibody(+) subgroups and antibody(-) subgroups. CONCLUSION: Arg60His variant in
      the LMP2 gene may be associated with the pathogenesis of AITD in Shanghai
      Chinese.

PMID- 12189116
TI  - Evaluating hematopoietic chimerism following allogeneic peripheral blood stem
      cell transplantation with microsatellites.
AB  - OBJECTIVE: To study the feasibility of using five selected tetranucleotide repeat
      sequences to detect chimerism in patients who underwent allogeneic peripheral
      blood stem cell transplantation and the correlation between chimerism status and
      prognosis in patients. METHODS: Genomic DNA of umbilical cord blood was colleted
      from 140 normal neonates. 5 loci including CSF1PO, D3S1359, D5S818, D17S1293 and
      D20S161in each sample were amplified with polymerase chain reaction  PCR  . PCR
      products were electrophoresed on PAGE gels  For each locus  fragments of
      different size were collected to analyze polymorphism  Genotypes of each sibling
      undergoing transplantation were analyzed at every locus to determine chimerism 
      For sex-mismatched transplantation  the amelogenin locus was analyzed to
      discriminate between kappa and Y chromosome  The correlation between chimerism
      and prognosis was studied. RESULTS: The four polymorphic symbols including the
      number of alleles and genotypes  the percentage of heterozygosity for each locus
      were as follows:for CSF1PO, 7 alleles and 16 genotypes were found; heterozygosity
      were separately 69.03%, for D3S1359, 12,26, 76.79%; for D5S818, 8, 21, 81.67%;
      for D17S1293, 12, 28, 79.09%; for D20S161, 7,17,79.67% and 0.7250  There were 12
      complete chimeras of which one died from graft-versus-host disease. One mixed
      chimera died two weeks following a second transplantation. The patient who had no
      donor-derived cells died too  The one whose chimerism transformed from mixed to
      complete after a second transplantation had no evidence of relapse. We could not
      determine which kind of chimerism the other two patients were. CONCLUSION:
      Chimerism after transplantation can be detected successfully with the five
      tetranucleotide repeat sequences  Every kind of chimerism has its respective
      prognosis  As the donor-derived cells decrease, the prognosis is becoming worse.

PMID- 12189118
TI  - Retrospective study on clinical features and risk factors of ventilator
      associated pneumonia.
AB  - OBJECTIVE: To deepen the understanding about ventilator-associated pneumonia
      (VAP). METHOD: Patients admitted to the respiratory intensive care unit from Jan 
      1996 approximately Oct  1999 were divided into two groups, with or without VAP,
      according to the diagnosis criteria. The comparative analysis was performed in
      clinical characteristics, risk factors, distribution of pathological organisms
      and prognosis. RESULTS: The incidence of VAP was 48.3% (28/58 cases). The cases
      with deep venous catheter in VAP group were much more than non-VAP group  P <
      0.05  . The duration of ventilation >/= 20 days among the patients of VAP group
      was 32.1%,while it was 6.7% in non-VAP group. 53 microorganisms were isolated
      from 25 patients with VAP. The main pathogens were  Acinetobacter spp  (32.1%),
      P. Aeruginosa  (20.8%) and C.albicans  (22.6%). The mortality rate of VAP group
      was 32.1%, significantly higher than that of non-VAP group (P < 0.05).
      CONCLUSIONS: The risk factors of VAP may be the use of deep venous catheter and
      long duration of ventilation. The main pathogens were Acinetobacter species,
      Pseudomonas aeruginosa,  and yeasts. The presence of VAP could significantly
      increase the mortality of patients.

PMID- 12189119
TI  - The expression of L-selectin at transcription and translation level in
      hemorrhagic shock rat.
AB  - OBJECTIVE: To detect the expression changes of L-selectin at levels of
      transcription and translation in hemorrhagic shock rats and to investigate the
      role of L-selectin in pathogenesis of trauma and hemorrhagic shock. METHODS: The
      tail-cut rats were set as normal group. The carotid puncture rats were set as
      control groups (trauma group); hemorrhagic shock model was established as shock
      group (hemorrhagic shock group). Every group has 8 rats. The surface expression
      of L-selectin in neutrophils was detected in the acute phase of hemorrhagic shock
      by flow cytometre. The mRNA expression of L-selectin was detected by reverse
      transcription polymerase chain reaction (RT-PCR ). RESULTS: The data showed that
      there were quantifiable kinetic changes in leukocyte after trauma and shock. N
      eutrophil L-selectin expression in tail-cut rats showed no significant change (P
      > 0.05) at different time points. The cell surface expression of L-selectin and
      its mRNA were up regulated in controls as compared with the normal group. The
      peak value of surface expression was at 3rd hour and last for 4-5 hours, while
      the peak value of mRNA was at 5th hour. As compared with the normal group, the
      values in the experimental group were up regulated in the early stage (P < 0.05),
      while in late stage they were down regulated after 3 hours (P < 0.05).
      CONCLUSIONS: The up-regulation of L-selectin in neutrophil after trauma may
      promote the adhesion of leucocytes to the wall of the venules and the
      inflammatory response may be benificial to wound healing and enhance the ability
      of anti-infection.The down-regulation of L-selectin after hemorrhagic shock may
      be associated with alleviation effects of the excessive adhesion reaction and may
      improve microcirculation.

PMID- 12189121
TI  - Claude-Bernard distinguished lecture. Physiology's recondite curriculum.

PMID- 12189120
TI  - Mycophenolate mofetil treatment for diffuse proliferative lupus nephritis: a
      multicenter clinical trial in China.
AB  - OBJECTIVE: To investigate the efficacy and side effects of mycophenolate mofetil
      (MMF) in the treatment of diffuse proliferative lupus nephritis( DPLN). METHODS:
      75 patients [13 male,62 female; age (31.0 +/- 10.1)y] with biopsy-proven active
      DPLN from nine hospitals in China from Jan. 1999 to Jan. 2000 were enrolled in
      this study, of whom 26 patients were refractory to conventional treatment of
      steroids and cyclophosphamide. 21 patients presented with relapses and 28
      patients were newly diagnosed. All the patients were treated with a combined
      regimen of MMF and steroids. Patients who had severe active renal lesions were
      initially given intravenous methylprednisolone followed by oral prednisone. The
      initial dosage of MMF was 0.5 approximately 2.0 g/d and the administrati on
      maintained at least 6 months. 38 patients had repeat renal biopsy after
      treatment. SLE disease activity (SLE-DAI) score, renal active index (AI),chronic
      index(CI) and density of immunoglobulins, complement deposition was assessed
      before and after MMF treatment. RESULTS: The mean starting dosage of MMF was
      (1.26 +/- 0.30) g/d, it was reduced to (1.21 +/- 0.30) g/d and (0.95 +/- 0.33)
      g/d at the end of the 3(rd) and 6(th) month respectively. The post-treatment Hb
      level increased from (92 +/- 21) g/L to (112 +/- 28) g/L(3 mo) and (116 +/- 21)
      g/L(6 mo), while proteinuria decreased from (4.24 +/- 2.66) g/d to (2.18 +/-
      3.75) g/d (3 mos, P < 0.05) and (1.54 +/- 1.60) g/d( 6 mos,P < 0.01). Renal
      function impairment present in some of the patients also showed marked
      improvement. The proportion of patients with positive A-dsDNA antibody and
      hypocomplementemia was significantly reduced after 6 months of MMF treatment. SLE
      DAI score in this group of patients decreased from (16.9 +/- 6.7) to (8.1 +/-
      4.8) (P < 0.01) by the end of 3 months. Repeat renal biopsy in 38 patients 3
      approximately 6 months after the treatment showed a significant decrement of AI (
      13.30 +/- 5.51) vs (3.38 +/- 1.98),P < 0.01, and an increment of CI (1.62 +/-
      1.48) vs (2.62 +/- 1.85), P > 0.05. Immunoglobulins and complement deposition
      scores decreased from (9.39 +/- 3.51) to(6.71 +/- 3.16 ),P < 0.05. During the
      study period, 12 episodes of infection (16.0%) were recorded including
      pneumonia(2.7%), herpes zoster(8.0 %), urinary tract infection(2.7%), and
      tuberculosis(2.7%). Other side effects included gastrointestinal symptoms
      (10.7%), hirsutism(6.7%), leukocytopenia (1.3%) and transient elevation of
      SGPT(2.7%). CONCLUSION: MMF in a dosage of 0.5 approximately 2.0 g/d combined
      with steroids is effective to control the lupus activity of DPLN and well
      tolerated by the patients.

PMID- 12189122
TI  - Transport of small molecules across cell membranes: water channels and urea
      transporters.
AB  - How do small hydrophilic nonelectrolytes cross cell membranes? Which pathways are
      most important for small lipid insoluble molecules to cross cell membranes? These
      are questions that have been basic to membrane transport physiology for decades.
      More importantly, these are questions whose answers have changed significantly
      within the last 10 years. This review discusses the evidence that pathways other
      than the lipid bilayer itself exist for the transport across cell membranes of
      specific small hydrophilic nonelectrolytes. The description begins with briefly
      analyzing the relevance of well accepted basic mathematical models for transport
      for understanding the permeability of representative physiologically important
      molecules across actual cell membranes. Particular emphasis is placed on
      describing recently discovered proteins that facilitate the transport of some of
      the smallest physiologically important lipid-insoluble molecules, water, and
      urea. Evidence also exists for transport proteins that selectively enhance the
      transmembrane transport of other small lipid-insoluble molecules. Do nonselective
      pores for small molecules exist in cell membranes?

PMID- 12189123
TI  - Sharing science: characteristics of effective scientist-teacher interactions.
AB  - Despite national guidelines to reform K-12 science education, our students are
      not learning science any better. Conducted under the auspices of the American
      Association for the Advancement of Science, a symposium examined several programs
      where professional scientists interact with classroom teachers to improve science
      education. Symposium participants described their projects and discussed the
      factors that contribute or detract from each project's success. The events of
      this symposium are critically analyzed. Four themes emerged as issues that affect
      the successful implementation and continuation of science education reform
      projects: scientific literacy as a primary goal, personal characteristics and
      commitment of project partners, curricular change built on social and
      developmental goals, and the incentive/reward structures in universities and
      school systems. This review of the emergent themes places the opinions of the
      symposium participants into the larger context of a growing science education
      research literature to inform others about synergy between professional
      scientists and classroom teachers. Our aim is to help others learn about the
      characteristics of effective partnerships to improve science education.

PMID- 12189124
TI  - Evolution of a partnership to improve K-16 science education.
AB  - This article grew out of a presentation at the 82nd Annual Meeting of the
      American Association for the Advancement of Science Pacific Division in Irvine,
      California in June 2001. The symposium "Sharing Science: Successful Scientist
      Expert-Teacher Practitioner Interactions" was organized by Drs. Nancy J. Pelaez
      and Barbara L. Gonzalez of California State University at Fullerton. Goodman's
      presentation was entitled "The Team Approach to Outreach Activities for K-12
      Teachers in a Large, Rural State." This personal view report describes the
      development and evolution of educational outreach programs at the University of
      South Dakota School of Medicine (USDSM) and the support provided by the
      administration. The number and strength of the programs at USDSM have grown in
      direct proportion to the commitment that the institution has been willing to make
      to faculty members with interests in science education. Currently, USDSM has
      three Basic Science faculty members who spend significant effort working with K
      12 students and teachers and who have been called upon nationally as consultants
      and reviewers for similar programs.

PMID- 12189125
TI  - Problem-based writing with peer review improves academic performance in
      physiology.
AB  - The aim of this study was to determine whether problem-based writing with peer
      review (PW-PR) improves undergraduate student performance on physiology exams.
      Didactic lectures were replaced with assignments to give students practice
      explaining their reasoning while solving qualitative problems, thus transferring
      the responsibility for abstraction and generalization to the students.
      Performance on exam items about concepts taught using PW-PR was compared with
      performance on concepts taught using didactic lectures followed by group work.
      Calibrated Peer Review, a Web-delivered program, was used to collect student
      essays and to manage anonymous peer review after students "passed" three
      calibration peer reviews. Results show that the students had difficulty relating
      concepts. Relationship errors were categorized as (1) problems recognizing levels
      of organization, (2) problems with cause/effect, and (3) overgeneralizations. For
      example, some described cells as molecules; others thought that vesicles
      transport materials through the extracellular fluid. With PW-PR, class discussion
      was used to confront and resolve such difficulties. Both multiple-choice and
      essay exam results were better with PW-PR instead of lecture.

PMID- 12189126
TI  - Simple experiments to understand the ionic origins and characteristics of the
      ventricular cardiac action potential.
AB  - Electrophysiological experiments are helpful for students to understand the role
      of electrical activity in heart function. Papillary muscle, which belongs to the
      ventricle, offers the advantage of being easily studied using glass
      microelectrodes. In addition, there is commercially available software that
      simulates ventricular electrical activity and can help overcome some
      difficulties, such as voltage clamp experiments, which need expensive apparatus
      when used for studies on living preparations. Here, we present a class practical
      session that is taken by undergraduate students at our University. In the first
      part of this class, students record action potentials from papillary muscles with
      the use of glass microelectrodes, and they change extracellular conditions to
      study the ionic basis of the action potential. In the second part of the class,
      students simulate action potentials using the Oxsoft Heart model (v. 4.0) and
      model their previous experiments on papillary muscle to quantify the effects. In
      particular, the model is very helpful in promoting understanding of the effect
      that extracellular potassium has on cardiac action potential by simulating
      voltage clamp experiments. This twin approach of papillary muscle experiments and
      computer modeling leads to a good understanding of the functioning of the action
      potential and can help introduce discussion of some abnormal cardiac functioning.

PMID- 12189127
TI  - What are the signaling pathways used by norepinephrine to contract the artery? A
      demonstration using guinea pig aortic ring segments.
AB  - The laboratory exercise described in this article used a simple preparation and a
      straightforward protocol to illustrate how the neurotransmitter norepinephrine
      (NE) induces an increase of tension in an artery. This was a practical class
      designed for undergraduate students of the University of Tours. The students
      performed several protocols to understand how NE acts to contract aortic ring
      vessels, which sources of calcium are mobilized, and whether the calcium
      sensitivity of the contractile regulatory apparatus is involved. The design of
      this exercise allowed students to participate actively in an exercise
      demonstrating that many mechanisms are involved and act additively to allow
      arterial tone to develop. Furthermore, the students were introduced to an
      isolated organ chamber technique that is used to study cellular mechanisms of
      many tissues and that is still important for smooth muscle research.

PMID- 12189128
TI  - Compelling classroom demonstrations that link visual system anatomy, physiology,
      and behaviour.
AB  - One of our approaches to teaching a course in anatomy and physiology is to stress
      the fundamental, systems-level concepts. One successful strategy we use is to
      continually highlight the relationships among anatomy, physiology, and behavior.
      In this article, we describe a set of classroom demonstrations that stress these
      links while fostering critical thinking. These demonstrations, on the topic of
      sensory system structure and function, rely on two perceptual consequences of
      neural adaptation in the visual system: afterimages and aftereffects. Viewing
      specific visual stimuli under binocular or monocular conditions with interocular
      transfer permits several concepts to be observed and discussed, including neural
      adaptation, anatomical and functional segregation of visual system pathways, and
      the relationship among visual system structure, function, and perception. This
      article discusses how to produce and present the required visual stimuli,
      suggests a set of questions to stimulate critical thinking, and presents student
      evaluation of this activity.

PMID- 12189129
TI  - Student critical thinking is enhanced by developing exercise prescriptions using
      online learning modules.
AB  - Developing the ability to think critically is an important element of
      undergraduate physiology education and is influenced by many factors, including
      the learning environment, the social context of the learning environment, and the
      instructor's approach to teaching. In this work, we describe online learning
      modules (OLM) that were designed to promote higher-order critical thinking skills
      in students enrolled in an upper-division Exercise Testing and Prescription
      course. The OLM provided students with an online learning environment in which to
      review clinical physiological details from authentic patient case data and
      develop exercise prescriptions (ExRx), by requiring students to critically
      analyze authentic patient case histories and collaborate on computer-based
      learning activities. On the basis of assessment data, we conclude that the OLM
      helped exercise science students develop the critical thinking skills necessary
      for development of effective exercise prescriptions by requiring them to think
      critically while concurrently reinforcing lecture-presented exercise science
      content.

PMID- 12189130
TI  - Spirometry: simulations of obstructive and restrictive lung diseases.

PMID- 12189131
TI  - Propagation of action potentials in myelinated vs. unmyelinated neurons.

PMID- 12189132
TI  - The C-terminal hinge region of lipoic acid-bearing domain of E2b is essential for
      domain interaction with branched-chain alpha-keto acid dehydrogenase kinase.
AB  - The branched-chain alpha-keto acid dehydrogenase (BCKD) kinase (abbreviated as
      BCK) down-regulates activity of the mammalian mitochondrial BCKD complex by
      reversible phosphorylation of the decarboxylase (E1b) component of the complex.
      The binding of BCK to the holotransacylase (E2b) core of the BCKD complex results
      in the stimulation of BCK activity. Here we show that the lipoylated lipoic acid
      bearing domain (lip-LBD) (residues 1-84) of E2b alone does not interact with BCK.
      However, lip-LBD constructs containing various lengths of the C-terminal hinge
      region of LBD are able to bind to BCK as measured by a newly developed solubility
      based binding assay. Isothermal titration calorimetry measurements produced a
      dissociation constant of 8.06 x 10(-6) m and binding enthalpy of -3.68 kcal/mol
      for the interaction of BCK with a construct containing lip-LBD and the Glu-Glu
      Asp-Xaa-Xaa-Glu sequence of the C-terminal hinge region of LBD. These
      thermodynamic parameters are similar to those obtained for binding of BCK to a
      lipoylated di-domain construct, which harbors LBD, the entire hinge region, and
      the downstream subunit-binding domain of E2b. Our data establish that the C
      terminal hinge region of LBD containing the above negatively charged residues is
      essential for the interaction between the lip-LBD construct and BCK.

PMID- 12189133
TI  - Phosphorylation-dependent scaffolding role of JSAP1/JIP3 in the ASK1-JNK
      signaling pathway. A new mode of regulation of the MAP kinase cascade.
AB  - JSAP1 (also termed JIP3) is a scaffold protein that interacts with specific
      components of the JNK signaling pathway. Apoptosis signal-regulating kinase (ASK)
      1 is a MAP kinase kinase kinase that activates the JNK and p38 mitogen-activated
      protein (MAP) kinase cascades in response to environmental stresses such as
      reactive oxygen species. Here we show that JSAP1 bound ASK1 and enhanced ASK1-
      and H(2)O(2)-induced JNK activity. ASK1 phosphorylated JSAP1 in vitro and in
      vivo, and the phosphorylation facilitated interactions of JSAP1 with SEK1/MKK4,
      MKK7 and JNK3. Furthermore, ASK1-dependent phosphorylation was required for JSAP1
      to recruit and thereby activate JNK in response to H(2)O(2). We thus conclude
      that JSAP1 functions not only as a simple scaffold, but it dynamically
      participates in signal transduction by forming a phosphorylation-dependent
      signaling complex in the ASK1-JNK signaling module.

PMID- 12189135
TI  - Using 2-aminopurine fluorescence to measure incorporation of incorrect
      nucleotides by wild type and mutant bacteriophage T4 DNA polymerases.
AB  - The ability of wild type and mutant T4 DNA polymerases to discriminate in the
      utilization of the base analog 2-aminopurine (2AP) and the fluorescence of 2AP
      were used to determine how DNA polymerases distinguish between correct and
      incorrect nucleotides. Because T4 DNA polymerase incorporates dTMP opposite 2AP
      under single-turnover conditions, it was possible to compare directly the kinetic
      parameters for incorporation of dTMP opposite template 2AP to the parameters for
      incorporation of dTMP opposite template A without the complication of enzyme
      dissociation. The most significant difference detected was in the K(d) for dTTP,
      which was 10-fold higher for incorporation of dTMP opposite template 2AP
      (approximately 367 microm) than for incorporation of dTMP opposite template A
      (approximately 31 microm). In contrast, the dTMP incorporation rate was reduced
      only about 2-fold from about 318 s(-1) with template A to about 165 s(-1) for
      template 2AP. Discrimination is due to the high selectivity in the initial
      nucleotide-binding step. T4 DNA polymerase binding to DNA with 2AP in the
      template position induces formation of a nucleotide binding pocket that is
      preshaped to bind dTTP and to exclude other nucleotides. If nucleotide binding is
      hindered, initiation of the proofreading pathway acts as an error avoidance
      mechanism to prevent incorporation of incorrect nucleotides.

PMID- 12189134
TI  - Regulation of HEF1 expression and phosphorylation by TGF-beta 1 and cell
      adhesion.
AB  - Transforming growth factor-beta1 (TGF-beta1) is a multipotential cytokine, which
      regulates remodeling of tissue extracellular matrix during early tumorigenesis
      and wound healing. Human enhancer of filamentation-1 (HEF1), a multifunctional
      docking protein, is involved in integrin-based signaling, which affects cell
      motility, growth, and apoptosis. Our studies reveal that TGF-beta1 is a potent
      inducer of HEF1 gene transcription in human dermal fibroblasts. TGF-beta1
      promoted HEF1 expression in a dose-dependent manner and resulted in a 16-fold
      increase in HEF1 protein level. TGF-beta1 had no effect on the stability of
      either HEF1 protein or mRNA. The TGF-beta1-induced HEF1 expression was
      independent of cell adhesion and resistant to cytoskeleton disruption. TGF-beta1
      increased levels of both p105 and p115 HEF1 in adherent fibroblasts. Digestion
      with specific phosphatases indicated that the p115HEF1 resulted from
      serine/threonine phosphorylation of p105HEF1. The appearance of the p115HEF1 as
      well as tyrosine phosphorylation of p105HEF1 required cell adhesion and/or an
      organized cytoskeleton. An in vitro kinase assay indicated that p105HEF1 was a
      substrate for Src. PP1, a specific Src kinase inhibitor, was able to block
      adhesion-dependent tyrosine phosphorylation of p105HEF1. These findings suggest
      that TGF-beta1 regulates HEF1 gene expression and that HEF1 phosphorylation is
      dependent on cell adhesion and Src kinase activity.

PMID- 12189136
TI  - Opposing effects of 15-lipoxygenase-1 and -2 metabolites on MAPK signaling in
      prostate. Alteration in peroxisome proliferator-activated receptor gamma.
AB  - Human prostate tumors have elevated levels of 15-lipoxygenase-1 (15-LOX-1) and
      data suggest that 15-LOX-1 may play a role in the development of prostate cancer.
      In contrast, 15-LOX-2 expression is higher in normal rather than in tumor
      prostate tissue and appears to suppress cancer development. We recently reported
      that 13-(S)-HODE, the 15-LOX-1 metabolite, up-regulates the MAP kinase signaling
      pathway and subsequently down-regulates PPARgamma in human colorectal carcinoma
      cells. To determine whether this mechanism is applicable to prostate cancer and
      what the effects of 15-LOX-2 are, we investigated the effect of 15-LOX-1, 15-LOX
      2, and their metabolites on epidermal growth factor (EGF)- and insulin-like
      growth factor (IGF)-1 signaling in prostate carcinoma cells. In PC3 cells, 13-(S)
      HODE, a 15-LOX-1 metabolite, up-regulated MAP kinase while in contrast 15-(S)
      HETE, a 15-LOX-2 metabolite, down-regulated MAP kinase. As a result, 13-(S)-HODE
      increased PPARgamma phosphorylation while a subsequent decrease in PPARgamma
      phosphorylation was observed with 15-(S)-HETE. Thus, 15-LOX metabolites have
      opposing effects on the regulation of the MAP kinase signaling pathway and a
      downstream target of MAP kinase signaling like PPARgamma. In addition to the EGF
      signaling pathway, the IGF signaling pathway appears to be linked to prostate
      cancer. 13-(S)-HODE and 15-(S)-HETE up-regulate or down-regulate, respectively,
      both the MAPK and Akt pathways after activation with IGF-1. Thus, the effect of
      these lipid metabolites is not solely restricted to EGF signaling and not solely
      restricted to MAPK signaling. These results provide a plausible mechanism to
      explain the apparent opposing effects 15-LOX-1 and 15-LOX-2 play in prostate
      cancer.

PMID- 12189137
TI  - Conformational changes of calpain from human erythrocytes in the presence of
      Ca2+.
AB  - Small angle x-ray scattering has been used to monitor calpain structural
      transitions during the activation process triggered by Ca(2+) binding. The
      scattering pattern of the unliganded enzyme in solution does not display any
      significant difference with that calculated from the crystal structure. The
      addition of Ca(2+) promotes the formation of large aggregates, indicating the
      exposure of hydrophobic patches on the surface of the protease. In contrast,
      Ca(2+) addition in the presence of the thiol proteinase inhibitor E64 or of the
      inhibitor leupeptin causes a small conformational change with no dissociation of
      the heterodimer. The resulting conformation appears to be slightly more extended
      than the unliganded form. From the comparison between ab initio models derived
      from our data with the crystal structure, the major observable conformational
      change appears to be localized at level of the L-subunit and in particular seems
      to confirm the mutual movement already observed by the crystallographic analysis
      of the dII (dIIb) and the dI (dIIa) domains creating a functional active site.
      This work not only provides another piece of supporting evidence for the calpain
      conformational change in the presence of Ca(2+), but actually constitutes the
      first experimental observation of this change for intact heterodimeric calpain in
      solution.

PMID- 12189138
TI  - Active site contribution to specificity of the aspartic proteases plasmepsins I
      and II.
AB  - Plasmepsins I and II (PM I and II) are aspartic proteases involved in the initial
      steps of Plasmodium hemoglobin degradation. They are attractive targets for
      antimalarial drug development. The two enzymes are 73% identical, yet have
      different substrate and inhibitor specificities. The x-ray structures of proform
      and mature PM II have been determined, but models of PM I do not adequately
      explain the selectivity of the two proteases. To better understand the basis of
      these recognition differences, we have identified nine residues of PM II that are
      in proximity to the inhibitor pepstatin in the crystal structure and differ in PM
      I. We mutated these residues in PM II to the cognate amino acids of PM I. Kinetic
      parameters for substrate and inhibitors for the PM II-mutant were similar to
      those of PM II-wild type (WT). Cleavage specificity was assessed using hemoglobin
      or a random decamer peptide library as substrate. Again, PM II-mutant behaved
      like PM II-WT rather than PM I-WT. These results indicate that differences in
      plasmepsin specificity depend more on conformational differences from distant
      sites than on specific active site variation.

PMID- 12189139
TI  - Alanine-scanning mutagenesis of alpha-helix D segment of interleukin-13 reveals
      new functionally important residues of the cytokine.
AB  - We documented that alpha-helices A, C, and D in human interleukin-13 (IL13)
      participate in interaction with its respective receptors. We hypothesized that
      alpha-helix D is the site II of the cytokine that binds IL13Ralpha1, a component
      of the normal tissue heterodimeric signaling IL13/4 receptor (IL13/4R), and that
      alpha-helix D independently binds a monomeric IL13Ralpha2 receptor, which is a
      non-signaling glioma-restricted receptor for IL13. Therefore, we alanine-scanned
      mutagenized helix D of IL13 to identify the residues involved in the respective
      receptors interaction. Recombinant muteins of IL13 were produced in Escherichia
      coli, and their structural integrity and identity were verified. The alanine
      mutants were tested in functional cellular assays, in which IL13 interaction with
      IL13Ralpha2 (glioma cells) or an ability to functionally stimulate IL13/4R (TF-1
      cells) were examined, and also in binding assays. We found that residues 105,
      106, and 109 of the d-helix of IL13 are responsible for interacting with the
      glioma-associated receptor. Moreover, glutamic acids at positions 92 and 110, and
      leucine at position 104 was found to be important for IL13/4R stimulation. Thus,
      alpha-helix D of IL13 is the primary site responsible for interaction with the
      IL13 binding proteins. We propose a model that illustrates the binding mode of
      IL13 with cancer-related IL13Ralpha2 and physiological IL13/4R.

PMID- 12189140
TI  - Radicicol-sensitive peptide binding to the N-terminal portion of GRP94.
AB  - GRP94 is a molecular chaperone that carries immunologically relevant peptides
      from cell to cell, transferring them to major histocompatibility proteins for
      presentation to T cells. Here we examine the binding of several peptides to
      recombinant GRP94 and study the regulation and site of peptide binding. We show
      that GRP94 contains a peptide-binding site in its N-terminal 355 amino acids. A
      number of peptides bind to this site with low on- and off-rates and with
      specificity that is distinct from that of another endoplasmic reticulum
      chaperone, BiP/GRP78. Binding to the N-terminal fragment is sufficient to account
      for the peptide binding activity of the entire molecule. Peptide binding is
      inhibited by radicicol, a known inhibitor of the chaperone activities of HSP90
      family proteins. However, the peptide-binding site is distinct from the radicicol
      binding pocket, because both can bind to the N-terminal fragment simultaneously.
      Furthermore, peptide binding does not cause the same conformational change as
      does binding of radicicol. When the latter binds to the N-terminal domain, it
      induces a conformational change in the downstream, acidic domain of GRP94, as
      measured by altered gel mobility and loss of an antibody epitope. These results
      relate the peptide-binding activity of GRP94 to its other function as a
      chaperone.

PMID- 12189141
TI  - Formation of complexes between Ca2+.calmodulin and the synapse-associated protein
      SAP97 requires the SH3 domain-guanylate kinase domain-connecting HOOK region.
AB  - Mammalian synapse-associated protein SAP97, a structural and functional homolog
      of Drosophila Dlg, is a membrane-associated guanylate kinase (MAGUK) that is
      present at pre- and postsynaptic sites as well as in epithelial cell-cell contact
      sites. It is a multidomain scaffolding protein that shares with other members of
      the MAGUK protein family a characteristic modular organization composed of three
      sequential protein interaction motifs known as PDZ domains, followed by an Src
      homology 3 (SH3) domain, and an enzymatically inactive guanylate kinase (GK)-like
      domain. Specific binding partners are known for each domain, and different modes
      of intramolecular interactions have been proposed that particularly involve the
      SH3 and GK domains and the so-called HOOK region located between these two
      domains. We identified the HOOK region as a specific site for calmodulin binding
      and studied the dynamics of complex formation of recombinant calmodulin and SAP97
      by surface plasmon resonance spectroscopy. Binding of various SAP97 deletion
      constructs to immobilized calmodulin was strictly calcium-dependent. From the
      rate constants of association and dissociation we determined an equilibrium
      dissociation constant K(d) of 122 nm for the association of calcium-saturated
      calmodulin and a SAP97 fragment, which encompassed the entire SH3-HOOK-GK module.
      Comparative structure-based sequence analysis of calmodulin binding regions from
      various target proteins predicts variable affinities for the interaction of
      calmodulin with members of the MAGUK protein family. Our findings suggest that
      calmodulin could regulate the intramolecular interaction between the SH3, HOOK,
      and GK domains of SAP97.

PMID- 12189142
TI  - Synaptotagmin-like protein (Slp) homology domain 1 of Slac2-a/melanophilin is a
      critical determinant of GTP-dependent specific binding to Rab27A.
AB  - The N-terminal synaptotagmin-like protein (Slp) homology domain (SHD) of the Slp
      and Slac2 families has recently been identified as a specific Rab27A-binding
      domain (Kuroda, T. S., Fukuda, M., Ariga, H., and Mikoshiba, K. (2002) J. Biol.
      Chem. 277, 9212-9218; Fukuda, M., Kuroda, T. S., and Mikoshiba, K. (2002) J.
      Biol. Chem. 277, 12432-12436). The SHD consists of two conserved alpha-helical
      regions (SHD1 and SHD2) that are often separated by two zinc finger motifs.
      However, the structural basis of Rab27A recognition by the SHD (i.e. involvement
      of each region (SHD1, zinc finger motifs, and SHD2) in Rab27A recognition and
      critical residue(s) for Rab27A/SHD interaction) had never been elucidated. In
      this study, systematic deletion analysis and Ala-based site-directed mutagenesis
      showed that SHD1 of Slac2-a/melanophilin alone is both necessary and sufficient
      for high affinity specific recognition of the GTP-bound form of Rab27A. By
      contrast, the zinc finger motifs and SHD2 are not an autonomous Rab27A-binding
      site and seem to be important for stabilization of the structure of the SHD or
      higher affinity Rab27A binding. In addition, chimeric analysis of Rab3A and
      Rab27A showed that the specific sequence of the switch II region of Rab27
      isoforms (especially Leu-84, Phe-88, and Asp-91 of Rab27A), which is not
      conserved in the Rab3 or Rab8 isoforms, is essential for recognition by the Slac2
      a SHD. Based on these findings, I propose that SHD1 of the Slp and Slac2 families
      be referred to as RBD27 (Rab-binding domain specific for Rab27 isoforms).

PMID- 12189143
TI  - Significance of GTP hydrolysis in Ypt1p-regulated endoplasmic reticulum to Golgi
      transport revealed by the analysis of two novel Ypt1-GAPs.
AB  - We here report on the identification and detailed biochemical characterization of
      two novel GTPase-activating proteins, Gyp5p and Gyp8p, whose efficient substrate
      is Ypt1p, a Ypt/Rab-GTPase essential for endoplasmic reticulum-to-Golgi
      trafficking in yeast. Gyp5p accelerated the intrinsic GTPase activity of Ypt1p
      4.2 x 10(4)-fold and, surprisingly, the 40-fold reduced GTP hydrolysis rate of
      Ypt1(Q67L)p 1.5 x 10(4)-fold. At steady state, the two newly discovered GTPase
      activating proteins (GAPs) as well as the previously described Gyp1p, which also
      uses Ypt1p as the preferred substrate, display different subcellular
      localization. To add to an understanding of the significance of Ypt1p-bound GTP
      hydrolysis in vivo, yeast strains expressing the GTPase-deficient Ypt1(Q67L)p and
      having different Ypt1-GAP genes deleted were created. Depending on the genetic
      background, different mutants exhibited growth defects at low temperature and,
      already at permissive temperature, various morphological alterations resembling
      autophagy. Transport of proteins was not significantly impaired. Growth defects
      of Ypt1(Q67L)-expressing cells could be suppressed on high expression of all
      three Ypt1-GAPs. We propose that permanently active Ypt1p leads to increased
      vesicle fusion, which might induce previously unnoticed autophagic degradation of
      exaggerated membrane-enclosed structures. The data indicate that hydrolysis of
      Ypt1p-bound GTP is a prerequisite for a balanced vesicle flow between endoplasmic
      reticulum and Golgi compartments.

PMID- 12189144
TI  - JNK phosphorylation and activation of BAD couples the stress-activated signaling
      pathway to the cell death machinery.
AB  - The c-Jun N-terminal kinase (JNK) signaling pathway plays a critical role in
      mediating apoptosis in the developing and mature organism. The JNK signaling
      pathway is thought to induce apoptosis via transcription-dependent and
      transcription-independent mechanisms that remain to be elucidated. In this study,
      we report a novel mechanism by which the JNK signaling pathway directly activates
      a component of the cell death machinery. We have found that JNK catalyzes the
      phosphorylation of the BH3-only protein BAD at the distinct site of serine 128 in
      vitro. Activation of the JNK signaling pathway induces the BAD serine 128
      phosphorylation in vivo, including in primary granule neurons of the developing
      rat cerebellum. The JNK-induced BAD serine 128 phosphorylation promotes the
      apoptotic effect of BAD in primary neurons by antagonizing the ability of growth
      factors to inhibit BAD-mediated apoptosis. These findings indicate that BAD is a
      novel substrate of JNK that links the stress-activated signaling pathway to the
      cell death machinery.

PMID- 12189145
TI  - Activation of human meprin-alpha in a cell culture model of colorectal cancer is
      triggered by the plasminogen-activating system.
AB  - The activation of latent proenzymes is an important mechanism for the regulation
      of localized proteolytic activity. Human meprin-alpha, an astacin-like zinc
      metalloprotease expressed in normal colon epithelial cells, is secreted as a
      zymogen into the intestinal lumen. Here, meprin is activated after propeptide
      cleavage by trypsin. In contrast, colorectal cancer cells secrete meprin-alpha in
      a non-polarized way, leading to accumulation and increased activity of meprin
      alpha in the tumor stroma. We have analyzed the activation mechanism of promeprin
      alpha in colorectal cancer using a co-culture model of the intestinal mucosa
      composed of colorectal adenocarcinoma cells (Caco-2) cultivated on filter
      supports and intestinal fibroblasts grown in the companion dish. We provide
      evidence that meprin-alpha is activated by plasmin and show that the presence of
      plasminogen in the basolateral compartment of the co-cultures is sufficient for
      promeprin-alpha activation. Analysis of the plasminogen-activating system in the
      co-cultures revealed that plasminogen activators produced and secreted by
      fibroblasts converted plasminogen to active plasmin, which in turn generated
      active meprin-alpha. This activation mechanism offers an explanation for the
      observed meprin-alpha activity in the tumor stroma, a prerequisite for a
      potential role of this protease in colorectal cancer.

PMID- 12189146
TI  - Mechanism of chaperone function in small heat shock proteins. Two-mode binding of
      the excited states of T4 lysozyme mutants by alphaA-crystallin.
AB  - To elucidate the mechanism of alphaA-crystallin chaperone function, a detailed
      thermodynamic analysis of its binding to destabilized, site-directed mutants of
      T4 lysozyme was carried out. The selected mutants form a ladder of stabilities
      spanning the 5-10 kcal/mol range of free energy of unfolding. The crystal
      structures of the majority of the mutants have been previously determined and
      found to be similar to that of the wild type with no evidence of static local
      unfolding. Complex formation between alphaA-crystallin and T4 lysozyme was
      observed directly via the changes in the electron paramagnetic resonance
      lineshape of a nitroxide introduced at a non-destabilizing, solvent exposed site
      in T4 lysozyme. AlphaA-crystallin differentially interacts with the mutants,
      binding the more destabilized ones to a larger extent despite the similar
      structure of their native states. Our results suggest that the states recognized
      by alphaA-crystallin are non-native excited states distinct from the unfolded
      state. Stable complexes are formed when the free energy of binding to alphaA
      crystallin is on the order of the free energy associated with the transition from
      the excited state to the native state. Biphasic binding isotherms reveal two
      modes of interactions with distinct affinities and stoichiometries. Highly
      destabilized mutants preferentially bind to the high capacity mode, suggesting
      conformational preference in the use of each mode. Furthermore, binding can be
      enhanced by increased temperature and pH, which may be reflecting conformational
      changes in alphaA-crystallin oligomeric structure.

PMID- 12189147
TI  - Shiga-like toxin inhibition of FLICE-like inhibitory protein expression
      sensitizes endothelial cells to bacterial lipopolysaccharide-induced apoptosis.
AB  - Shiga-like toxin (SLT) has been implicated in the pathogenesis of hemolytic
      uremic syndrome and its attendant endothelial cell (EC) injury. Key serotypes of
      Escherichia coli produce SLT-1 in addition to another highly pro-inflammatory
      molecule, lipopolysaccharide (LPS). It has previously been established that SLT-1
      induces EC apoptosis and that LPS enhances this effect. LPS alone has no affect
      on human EC viability, and the mechanism for this enhancement remains unknown. In
      the present report, we demonstrate that SLT-1 sensitizes EC to LPS-induced
      apoptosis. Pretreatment with SLT-1 sensitized EC to LPS-induced apoptosis,
      whereas pretreatment with LPS did not influence SLT-1-induced apoptosis. SLT-1
      exposure resulted in decreased expression of FLICE-like inhibitory protein
      (FLIP), an anti-apoptotic protein that has previously been shown to block LPS
      induced apoptosis. This SLT-1-mediated decrease in FLIP expression preceded the
      onset of apoptosis elicited by SLT-1 alone or in combination with LPS. SLT-1
      mediated decrements in FLIP expression correlated in a dose- and time-dependent
      manner with sensitization to LPS-induced apoptosis. Finally, transient or stable
      overexpression of FLIP protected against LPS enhancement of SLT-1-induced
      apoptosis, and this protection corresponded with sustained expression of FLIP.
      Together, these data suggest that SLT-1 sensitizes EC to LPS-induced apoptosis by
      inhibiting FLIP expression.

PMID- 12189148
TI  - A p21-activated kinase-controlled metabolic switch up-regulates phagocyte NADPH
      oxidase.
AB  - Chemoattractant-stimulated phagocytes increase their glucose uptake and divert
      energy production from glycolysis to the pentose phosphate pathway to generate
      NADPH. NADPH is a required cofactor for the NADPH oxidase to produce reactive
      oxygen metabolites, an important microbicidal tool in host defense. p21-Activated
      kinases (Paks) are regulated by the GTPases Rac and Cdc42 and control actin
      dynamics and phosphorylation of the oxidase component p47(phox). Here we report
      the interaction of Pak with phosphoglycerate mutase (PGAM)-B, an enzyme of the
      glycolytic pathway. Activated Pak1 inhibits glycolysis by association of its
      catalytic domain with PGAM-B and subsequent phosphorylation of the enzyme on
      serine residues 23 and 118, thereby abolishing PGAM activity. Leukocyte
      activation through chemoattractant receptors leads to Pak activation and
      transient inhibition of endogenous PGAM-B activity. Consistent with these
      observations, treatment of neutrophils with phosphoglycolic acid, a competitive
      PGAM-B inhibitor, increases upstream intermediates, thereby amplifying the
      respiratory burst. These results demonstrate that Rho GTPases regulate the
      glycolytic pathway through Pak and suggest a link between chemoattractant
      signaling and metabolic responses to enhance host defense.

PMID- 12189149
TI  - Molecular characterization of a novel, cadmium-inducible gene from the nematode
      Caenorhabditis elegans. A new gene that contributes to the resistance to cadmium
      toxicity.
AB  - Cadmium is an environmental contaminant that is both a human toxicant and
      carcinogen. To inhibit cadmium-induced damage, cells respond by increasing the
      expression of genes that encode stress-response proteins. We previously reported
      the identification of 48 cadmium-inducible mRNAs in the nematode Caenorhabditis
      elegans. Here we describe a new cadmium-responsive gene, designated cdr-1, whose
      rate and level of inducible expression parallel those of the C. elegans
      metallothioneins. The CDR-1 mRNA contains an open reading frame of 831 bp and
      encodes a predicted 32-kDa, integral membrane protein. Following cadmium
      exposure, cdr-1 is transcribed exclusively in intestinal cells of post-embryonic
      C. elegans. In vivo, the CDR-1 protein is targeted specifically to the intestinal
      cell lysosomes. cdr-1 transcription is significantly induced by cadmium but not
      by other tested stressors. These results indicate that cdr-1 expression is
      regulated by cadmium and in a cell-specific fashion. Inhibition of CDR-1
      expression renders C. elegans susceptible to cadmium toxicity. In conclusion, cdr
      1 defines a new class of cadmium-inducible genes and encodes an integral
      membrane, lysosomal protein. This protein functions to protect against cadmium
      toxicity.

PMID- 12189150
TI  - Proline-rich cell surface antigens of horseshoe crab hemocytes are substrates for
      protein cross-linking with a clotting protein coagulin.
AB  - Monoclonal antibodies were raised against hemocytes of the horseshoe crab
      Tachypleus tridentatus. All of the antibodies obtained reacted with the same
      protein bands on SDS-PAGE of hemocyte lysate. Flow cytometry and biotinylation of
      surface substances on the hemocytes indicated that the antigens are major
      peripheral proteins of hemocytes. The antigens were purified from hemocyte lysate
      and were good substrates for the horseshoe crab hemocyte transglutaminase
      (HcTGase). Transglutaminases play an important role during the final stage of
      blood coagulation in mammals and crustaceans. Although HcTGase did not
      intermolecularly cross-link a clottable protein coagulogen or its proteolytic
      product coagulin, HcTGase promoted the cross-linking of coagulin with the surface
      antigens, resulting in the formation of a stable polymer. We determined the
      nucleotide sequences for two isoproteins of the antigens. The two proteins
      containing 271 and 284 residues (66% identity) were composed of tandem repeats of
      proline-rich segments. We named them proxins-1 and -2 after proline-rich proteins
      for protein cross-linking. Proxins may form a stable physical barrier against
      invading pathogens in cooperation with hemolymph coagulation at injured sites.

PMID- 12189151
TI  - Malarial dihydroorotate dehydrogenase. Substrate and inhibitor specificity.
AB  - The malarial parasite relies on de novo pyrimidine biosynthesis to maintain its
      pyrimidine pools, and unlike the human host cell it is unable to scavenge
      preformed pyrimidines. Dihydroorotate dehydrogenase (DHODH) catalyzes the
      oxidation of dihydroorotate (DHO) to produce orotate, a key step in pyrimidine
      biosynthesis. The enzyme is located in the outer membrane of the mitochondria of
      the malarial parasite. To characterize the biochemical properties of the malarial
      enzyme, an N-terminally truncated version of P. falciparum DHODH has been
      expressed as a soluble, active enzyme in E. coli. The recombinant enzyme binds
      0.9 molar equivalents of the cofactor FMN and it has a pH maximum of 8.0 (k(cat)
      8 s(-1), K(m)(app) DHO (40-80 microm)). The substrate specificity of the
      ubiquinone cofactor (CoQ(n)) that is required for the oxidation of FMN in the
      second step of the reaction was also determined. The isoprenoid (n) length of
      CoQ(n) was a determinant of reaction efficiency; CoQ(4), CoQ(6) and
      decylubiquinone (CoQ(D)) were efficiently utilized in the reaction, however
      cofactors lacking an isoprenoid tail (CoQ(0) and vitamin K(3)) showed decreased
      catalytic efficiency resulting from a 4 to 7-fold increase in K(m)(app). Five
      potent inhibitors of mammalian DHODH, Redoxal, dichloroallyl lawsone (DCL), and
      three analogs of A77 1726 were tested as inhibitors of the malarial enzyme. All
      five compounds were poor inhibitors of the malarial enzyme, with IC(50)'s ranging
      from 0.1-1.0 mm. The IC(50) values for inhibition of the malarial enzyme are
      10(2)-10(4)-fold higher than the values reported for the mammalian enzyme,
      demonstrating that inhibitor binding to DHODH is species specific. These studies
      provide direct evidence that the malarial DHODH active site is different from the
      host enzyme, and that it is an attractive target for the development of new anti
      malarial agents.

PMID- 12189152
TI  - The tetraspan protein epithelial membrane protein-2 interacts with beta1
      integrins and regulates adhesion.
AB  - The growth arrest-specific-3 (GAS3)/PMP22 proteins are members of the four
      transmembrane (tetraspan) superfamily. Although the function of these proteins is
      poorly understood, GAS3/PMP22 proteins have been implicated in the control of
      growth and progression of certain cancers. Epithelial membrane protein-2 (EMP2),
      a GAS3/PMP22 family member, was recently identified as a putative tumor
      suppressor gene. Here, we addressed the normal function of EMP2 by testing the
      prediction that it influences integrin-related cell functions. We observed that
      EMP2 associates with the beta(1) integrin subunit. Co-immunoprecipitation and
      immunodepletion experiments indicated that approximately 60% of beta(1) integrins
      and EMP2 can be isolated in common protein complexes. Whereas this association
      between EMP2 and beta(1) integrin may be direct or indirect, it has features of
      integrin heterodimer selectivity. Thus, by laser confocal microscopy, EMP2
      colocalized with alpha(6)beta(1) but not alpha(5)beta(1) integrin. Increased
      expression of EMP2 also influenced the integrin heterodimer repertoire present on
      the plasma membrane. EMP2 specifically increased the surface expression of the
      alpha(6)beta(1) integrin while decreasing that of the alpha(5)beta(1) protein.
      Reciprocally, reduction in EMP2 expression using a specific ribozyme decreased
      surface expression of alpha(6)beta(1) integrin. Accordingly, these EMP2-mediated
      changes resulted in a dramatic alteration in cellular adhesion to extracellular
      matrix proteins. This study demonstrates for the first time the interaction of a
      GAS3/PMP22 family member with an integrin protein and suggests that such
      interactions and their functional consequences are a physiologic role of
      GAS3/PMP22 proteins.

PMID- 12189153
TI  - Inhibition of adipocyte differentiation by resistin-like molecule alpha.
      Biochemical characterization of its oligomeric nature.
AB  - A novel family of cysteine-rich secreted proteins with unique tissue distribution
      has recently been identified. One of the members, resistin (for "resistance to
      insulin"), also called FIZZ3, was identified in a screen for molecules that are
      down-regulated in mature adipocytes upon administration of thiazolidinediones.
      The prototypical member of this family was originally identified from
      bronchoalveolar lavage fluid of inflamed lungs and designated FIZZ1 ("found in
      inflammatory zone"). This molecule was also found to be highly expressed in
      adipose tissue and was named resistin-like molecule alpha (RELMalpha). Here we
      demonstrate that RELMalpha inhibits the differentiation of 3T3-L1 preadipocytes
      into adipocytes. RELMalpha has no effect on proliferation of 3T3-L1
      preadipocytes. Pretreatment of 3T3-L1 preadipocytes with RELMalpha does not
      affect insulin- or platelet-derived growth factor-induced mitogenesis. IRS-1
      phosphorylation and glucose transport stimulated by insulin in mature adipocytes
      were also unaffected by RELMalpha. We show that RELMalpha forms disulfide-linked
      homooligomers based on results from electrophoresis under reducing and
      nonreducing conditions, coimmunoprecipitation experiments as well as by mass
      spectrometry. In addition, RELMalpha is able to form heterooligomers with
      resistin but not RELMbeta. Since RELMalpha is expressed by adipose tissue and it
      is a secreted factor, our findings suggest that RELMalpha may be involved in the
      control of the adipogenesis as well as in the process of muscle differentiation.

PMID- 12189154
TI  - Characterization of four murine homologs of the human ov-serpin monocyte
      neutrophil elastase inhibitor MNEI (SERPINB1).
AB  - The human ov-serpin monocyte neutrophil elastase inhibitor (MNEI) is encoded by a
      single gene SERPINB1. It is a highly efficient inhibitor of neutrophil granule
      proteases. Four murine genes with high sequence identity with MNEI were
      identified and fully sequenced, and these were named EIA, EIB, EIC, and EID. EIA,
      EIB and EIC showed the same seven-exon gene structure as SERPINB1. However, EIC
      included an additional, alternatively spliced, exon due to the insertion of an
      endogenous retrovirus-like sequence. EID lacked several exons and is a
      pseudogene. Reverse transcriptase-PCR showed that EIA, like MNEI, is expressed at
      high levels in many tissues. EIB is mainly expressed in brain, and EIC was only
      expressed as splicing variants unlikely to encode a functional serpin. Upon
      incubation with serine proteases, EIA formed inhibitory covalent complexes with
      pancreatic and neutrophil elastases, cathepsin G, proteinase-3, and chymotrypsin,
      as previously shown for MNEI, whereas EIB was only able to do so with cathepsin
      G. According to the new serpin nomenclature, the genes encoding EIA, EIB, EIC,
      and EID will be called Serpinb1, Serpinb1b, Serpinb1c, and Serpinb1-ps1. These
      data demonstrate that the four murine homologs of MNEI have met different
      evolutionary fates, and that EIA is the mouse ortholog of MNEI.

PMID- 12189155
TI  - Regulation of cAMP-dependent protein kinase activity by glutathionylation.
AB  - The catalytic subunit of cAMP-dependent protein kinase (cAPK) is susceptible to
      inactivation by a number of thiol-modifying reagents. Inactivation occurs through
      modification of cysteine 199, which is located near the active site. Because
      cysteine 199 is reactive at physiological pH, and modification of this site
      inhibits activity, we hypothesized that cAPK is a likely target for regulation by
      an oxidative mechanism, specifically glutathionylation. In vitro studies
      demonstrated the susceptibility of kinase activity to the sulfhydryl oxidant
      diamide, which inhibited by promoting an intramolecular disulfide bond between
      cysteines 199 and 343. In the presence of a low concentration of diamide and
      reduced glutathione, the kinase was rapidly and reversibly inhibited by
      glutathionylation. Mutant kinase containing an alanine to cysteine mutation at
      position 199 was resistant to inhibition by both diamide and glutathionylation,
      thus implicating this as the oxidation-sensitive site. Mouse fibroblast cells
      treated with diamide showed a reversible decrease in cAPK activity. Inhibition
      was dramatically enhanced when cells were first treated with cAPK activators.
      Using biotin-cysteine as means for detecting and purifying thiolated cAPK from
      cells, we were able to show that, under conditions in which cAPK is inactivated
      by diamide, it is also readily thiolated.

PMID- 12189157
TI  - The N terminus of mannose 6-phosphate/insulin-like growth factor 2 receptor in
      regulation of fibrinolysis and cell migration.
AB  - Leukocyte migration to sites of inflammation is a multistep process involving
      transient adhesion to the endothelium followed by cell surface-controlled
      proteolysis for transmigration through the vessel wall and chemotactic movement
      within tissues. One of the key players in this machinery appears to be the
      urokinase-type plasminogen activator (uPA)/uPA receptor system. The role of uPA
      and its receptor (CD87) in plasminogen (Plg) activation, cell adhesion, and
      chemotaxis is well established; however, less is known of how these activities
      are regulated. Here we provide evidence that the mannose 6-phosphate/insulin-like
      growth factor 2 receptor (CD222) controls CD87-mediated functions. Expression of
      human CD222 in CD222-/- mouse fibroblasts down-regulated Plg activation, cell
      adhesion, and chemotaxis induced by the uPA/CD87 system. In addition, we
      demonstrate that the N-terminal region of CD222, which is similar to the Plg
      binding site of streptokinase, plays a crucial role in binding of CD87 and Plg. A
      peptide derived from this region in CD222 is able to disrupt the physical
      interaction of CD222 with CD87 and, furthermore, mimics the inhibitory effects of
      CD222 on CD87 functions. Taken together, our results indicate a novel role for
      CD222 in regulation of fibrinolysis, cell adhesion, and migration.

PMID- 12189156
TI  - Subcellular targeting and agonist-induced site-specific phosphorylation of
      endothelial nitric-oxide synthase.
AB  - The endothelial isoform of nitric-oxide synthase (eNOS) undergoes a complex
      pattern of covalent modifications, including acylation with the fatty acids
      myristate and palmitate as well as phosphorylation on multiple sites. eNOS
      acylation is a key determinant for the reversible subcellular targeting of the
      enzyme to plasmalemmal caveolae. We transfected a series of hemagglutinin epitope
      tagged eNOS mutant cDNAs deficient in palmitoylation (palm(-)) and/or
      myristoylation (myr(-)) into bovine aortic endothelial cells; after treatment
      with the eNOS agonists sphingosine 1-phosphate or vascular endothelial growth
      factor, the recombinant eNOS was immunoprecipitated using an antibody directed
      against the epitope tag, and patterns of eNOS phosphorylation were analyzed in
      immunoblots probed with phosphorylation state-specific eNOS antibodies. The wild
      type eNOS underwent agonist-induced phosphorylation at serine 1179 (a putative
      site for phosphorylation by kinase Akt), but phosphorylation of the myr(-) eNOS
      at this residue was nearly abrogated; the palm(-) eNOS exhibited an intermediate
      phenotype. The addition of the CD8 transmembrane domain to the amino terminus of
      eNOS acylation-deficient mutants rescued the wild-type phenotype of robust
      agonist-induced serine 1179 phosphorylation. Thus, membrane targeting, but not
      necessarily acylation, is the critical determinant for agonist-promoted eNOS
      phosphorylation at serine 1179. In striking contrast to serine 1179,
      phosphorylation of eNOS at serine 116 was enhanced in the myr(-) eNOS mutant and
      was markedly attenuated in the CD8-eNOS membrane-targeted fusion protein. We
      conclude that eNOS targeting differentially affects eNOS phosphorylation at
      distinct sites in the protein and suggest that the inter-relationships of eNOS
      acylation and phosphorylation may modulate eNOS localization and activity and
      thereby influence NO signaling pathways in the vessel wall.

PMID- 12189158
TI  - Proteomics and models for enzyme cooperativity.

PMID- 12189159
TI  - Multiple functions of caveolin-1.

PMID- 12189160
TI  - Founder TIGR/myocilin mutations for glaucoma in the Quebec population.
AB  - Primary open-angle glaucoma (POAG) is a complex disorder characterized by a
      progressive and treatable degeneration of the optic nerve. TIGR/myocilin (MYOC)
      gene mutations are found in approximately 4% of all POAG patients. Populations
      with frequent founder effects, such as the French-Canadians, offer unique
      advantages to implement genetic testing for the disorder. To assess molecular
      diagnosis for POAG in this population, we determined the prevalence of TIGR/MYOC
      mutations in 384 unrelated glaucoma patients, 38 ocular hypertensive subjects and
      18 affected families (180 patients). We further analyzed the clinical features
      associated with these variations. Nine coding sequence variants were defined as
      mutations causing mostly, but not exclusively, POAG. Four families segregated
      distinct mutations (Gly367Arg, Gln368Stop, Lys423Glu and Pro481Leu), while 14
      unrelated glaucoma patients harbored six known mutations (Thr293Lys, Glu352Lys,
      Gly367Arg, Gln368Stop, Lys423Glu and Ala445Val) and two novel (Ala427Thr and
      Arg126Trp). The frequencies of these mutations were respectively 3.8% and 22.2%
      in the unrelated and family studies. The Gly367Arg and Lys423Glu variants caused
      the earliest ages at onset. When achievable, assessment of relatives of unrelated
      mutation carriers showed the Arg126Trp and Gly367Arg to be familial.
      Characteristic allele signatures, indicative of specific founder effects, were
      observed for five of the six mutations conveyed by at least two patients.
      Recombination probability estimates suggested that the French-Canadian population
      had most probably inherited these six mutations from 7-10 Quebec settlers. Our
      data demonstrated that genetic screening for TIGR/MYOC mutations should be
      offered to glaucoma families and to close relatives of unrelated patients aware
      of a family history for the disorder.

PMID- 12189161
TI  - Defective de novo methylation of viral and cellular DNA sequences in ICF syndrome
      cells.
AB  - ICF syndrome (immunodeficiency, centromere instability and facial anomalies) is a
      recessive human genetic disorder resulting from mutations in the DNA
      methyltransferase 3B (DNMT3B) gene. Patients with this disease exhibit numerous
      chromosomal abnormalities, including anomalous decondensation, pairing,
      separation and breakage, primarily involving the pericentromeric regions of
      chromosomes 1 and 16. Global levels of DNA methylation in ICF cells are only
      slightly reduced; however, certain repetitive sequences and genes on the inactive
      X chromosome of female ICF patients are significantly hypomethylated. In the
      present report, we analyze the molecular defect of de novo methylation in ICF
      cells in greater detail by making use of a model Epstein-Barr virus (EBV)-based
      system and three members of the unique cellular cancer-testis (C-T) gene family.
      Results with the EBV-based system indicate that de novo methylation of newly
      introduced viral sequences is defective in ICF syndrome. Limited de novo
      methylation capacity is retained in ICF cells, indicating that the mutations in
      DNMT3B are not complete loss-of-function mutations or that other DNMTs cooperate
      with DNMT3B. Analysis of three C-T genes (two on the X chromosome and one
      autosomal) revealed that loss of methylation from cellular gene sequences is
      heterogeneous, with both autosomal and X chromosome-based genes demonstrating
      sensitivity to mutations in DNMT3B. Aberrant hypomethylation at a number of loci
      examined correlated with altered gene expression levels. Lastly, no consistent
      changes in the protein levels of the DNA methyltransferases were noted when
      normal and ICF cell lines were compared.

PMID- 12189162
TI  - A mouse model of spinal and bulbar muscular atrophy.
AB  - Spinal and bulbar muscular atrophy (SBMA) is an adult-onset motor neuron disease,
      caused by the expansion of a trinucleotide repeat (TNR) in exon 1 of the androgen
      receptor (AR) gene. This disorder is characterized by degeneration of motor and
      sensory neurons, proximal muscular atrophy, and endocrine abnormalities, such as
      gynecomastia and reduced fertility. We describe the development of a transgenic
      model of SBMA expressing a full-length human AR (hAR) cDNA carrying 65 (AR(65))
      or 120 CAG repeats (AR(120)), with widespread expression driven by the
      cytomegalovirus promoter. Mice carrying the AR(120) transgene displayed
      behavioral and motor dysfunction, while mice carrying 65 CAG repeats showed a
      mild phenotype. Progressive muscle weakness and atrophy was observed in AR(120)
      mice and was associated with the loss of alpha-motor neurons in the spinal cord.
      There was no evidence of neurodegeneration in other brain structures. Motor
      dysfunction was observed in both male and female animals, showing that in SBMA
      the polyglutamine repeat expansion causes a dominant gain-of-function mutation in
      the AR. The male mice displayed a progressive reduction in sperm production
      consistent with testis defects reported in human patients. These mice represent
      the first model to reproduce the key features of SBMA, making them a useful
      resource for characterizing disease progression, and for testing therapeutic
      strategies for both polyglutamine and motor neuron diseases.

PMID- 12189163
TI  - Homozygosity for a missense mutation in fibulin-5 (FBLN5) results in a severe
      form of cutis laxa.
AB  - Hereditary cutis laxa comprises a heterogeneous group of connective tissue
      disorders characterized by loose skin and variable systemic involvement.
      Autosomal dominant and recessive as well as X-linked forms have been described.
      Some dominant forms are caused by mutations in the elastine gene (ELN). The X
      linked form is now classified in the group of copper transport diseases. The
      genetic defect underlying the autosomal recessive (AR) forms of cutis laxa is not
      known. The phenotypic abnormalities recently observed in a fibulin-5 knockout
      mouse model are reminiscent of human AR cutis laxa type I. Both share cutis laxa,
      lung emphysema and arterial involvement. Molecular study of the fibulin-5 (FBLN5)
      gene in a large consanguineous Turkish family with four patients affected by AR
      cutis laxa type I demonstrated the presence of a homozygous missense mutation
      (T998C) in the FBLN5 gene resulting in a serine-to-proline (S227P) substitution
      in the fourth calcium-binding epidermal growth factor-like domain of fibulin-5
      protein. This amino acid substitution is predicted to have important structural
      and functional consequences for normal elastogenesis. As such, we provide
      evidence that a genetic defect in fibulin-5 (FBLN5, also known as EVEC or DANCE)
      is responsible for a recessive form of cutis laxa in humans.

PMID- 12189164
TI  - A mutation in the gene TNFRSF11B encoding osteoprotegerin causes an idiopathic
      hyperphosphatasia phenotype.
AB  - Idiopathic hyperphosphatasia is an autosomal recessive bone disease characterized
      by deformities of long bones, kyphosis and acetabular protrusion, increasing in
      severity as affected children pass through adolescence. Biochemical and
      histological evidence indicate that there is extremely rapid bone turnover, with
      indices of both bone resorption and formation greatly increased. A genome-wide
      search, in a family with three children affected by idiopathic hyperphosphatasia,
      suggested linkage to a locus on the long arm of chromosome 8 (8q24). The gene
      TNFRSF11B encoding osteoprotegerin (OPG), which lies within this locus, was an
      obvious candidate, given the critical role of OPG in regulating osteoclast
      development. All three affected siblings were homozygous for a 3 bp inframe
      deletion in exon 3 of the TNFRSF11B gene, resulting in the loss of an aspartate
      residue. Their parents (who were first cousins) were heterozygous for the
      mutation. Recombinant wild-type and mutant OPG cDNAs were expressed in human
      epithelial kidney cells, and secreted OPG was collected from the conditioned
      medium. In vitro measurements of bone resorption showed that wild-type OPG
      suppressed bone resorption, whereas the mutant form did not, confirming this to
      be an inactivating mutation. This description of abnormal OPG function in humans
      expands the spectrum of genetic bone diseases arising from perturbations of the
      OPG/RANK-L/RANK system that regulates osteoclastogenesis.

PMID- 12189165
TI  - Motifs within the CLN3 protein: modulation of cell growth rates and apoptosis.
AB  - Juvenile Batten disease (JNCL) is an autosomal recessive disease that results
      from mutations in the CLN3 gene. The wild-type CLN3 gene coding sequence has 15
      exons, and the translated protein consists of 438 amino acids. The most commonly
      observed mutation is a 1.02 kb deletion in the genomic DNA. This deletion results
      in a truncated protein due to the loss of amino acids 154-438, and the
      introduction of 28 novel amino acids at the c-terminus. We demonstrate that,
      compared to normal controls, CLN3-deficient immortalization of lymphoblasts
      homozygous for this deletion grow at a slower rate, and show increased
      sensitivity to etoposide-induced apoptosis, supporting the notion that CLN3 may
      negatively regulate apoptosis. Using immortalized JNCL lymphoblast cell lines as
      a model system, we assess the effects of specific CLN3 mutations on cell growth
      rates and protection from etoposide-induced apoptosis. Protection from etoposide
      induced apoptosis occurs and the cell growth rate is restored following
      transfection of JNCL lymphoblasts with mutant CLN3 cDNA that includes exons 11 or
      13. We show that deletion of the glycosylation sites 71NQSH74 and 310NTSL313, and
      also mutations within the highly conserved amino acid stretches
      184WSSGTGGAGLLG195, 291VYFAE295 and 330VFASRSSL337, result in slowed growth and
      susceptibility to apoptosis.

PMID- 12189166
TI  - Identification of the autoantigen SART-1 as a candidate gene for the development
      of atopy.
AB  - The possibility that immune responses to autoantigens may contribute to the
      development of atopic disease has been largely ignored. In this paper, we
      describe the chromosomal localization of the gene for squamous cell carcinoma
      associated reactive antigen for cytotoxic T cells (SART-1). The SART-1 gene
      localized to a region of 11q12-13 showing strong linkage to atopy in previous
      studies. Further analysis of this gene revealed the presence of at least 20 exons
      of varying lengths and four novel single-nucleotide polymorphisms, one of which
      resulted in an amino acid substitution. Association analysis in families
      recruited on the basis of affected sib pairs for asthma reveal significant
      association for both coding region polymorphisms with atopy. We therefore
      hypothesize that polymorphic variation within the SART-1 gene may account for
      individuals developing atopy.

PMID- 12189167
TI  - Zeta-sarcoglycan, a novel component of the sarcoglycan complex, is reduced in
      muscular dystrophy.
AB  - The dystrophin glycoprotein complex (DGC) is found at the plasma membrane of
      muscle cells, where it provides a link between the cytoskeleton and the
      extracellular matrix. A subcomplex within the DGC, the sarcoglycan complex,
      associates with dystrophin and mediates muscle membrane stability. Mutations in
      sarcoglycan genes lead to muscular dystrophy and cardiomyopathy in both humans
      and mice. In invertebrates, there are three sarcoglycan genes, while in mammals
      there are additional sarcoglycan genes that probably arose from gene duplication
      events. We identified a novel mammalian sarcoglycan, zeta-sarcoglycan, that is
      highly related to gamma-sarcoglycan and delta-sarcoglycan. We generated a zeta
      sarcoglycan-specific antibody and found that zeta-sarcoglycan associated with
      other members of the sarcoglycan complex at the plasma membrane. Additionally,
      zeta-sarcoglycan was reduced at the membrane in muscular dystrophy, consistent
      with a role in mediating membrane stability. zeta-Sarcoglycan was also found as a
      component of the vascular smooth muscle sarcoglycan complex. Together, these data
      demonstrate that zeta-sarcoglycan is an integral component of the sarcoglycan
      complex and, as such, is important in the pathogenesis of muscular dystrophy.

PMID- 12189168
TI  - Sustained hepatic and renal glucose-6-phosphatase expression corrects glycogen
      storage disease type Ia in mice.
AB  - Deficiency of glucose-6-phosphatase (G6Pase), a key enzyme in glucose
      homeostasis, causes glycogen storage disease type Ia (GSD-Ia), an autosomal
      recessive disorder characterized by growth retardation, hypoglycemia,
      hepatomegaly, nephromegaly, hyperlipidemia, hyperuricemia, and lactic acidemia.
      G6Pase is an endoplasmic reticulum-associated transmembrane protein expressed
      primarily in the liver and the kidney. Therefore, enzyme replacement therapy is
      not feasible using current strategies, but somatic gene therapy, targeting G6Pase
      to the liver and the kidney, is an attractive possibility. Previously, we
      reported the development of a mouse model of G6Pase deficiency that closely
      mimics human GSD-Ia. Using neonatal GSD-Ia mice, we now demonstrate that a
      combined adeno virus and adeno-associated virus vector-mediated gene transfer
      leads to sustained G6Pase expression in both the liver and the kidney and
      corrects the murine GSD-Ia disease for at least 12 months. Our results suggest
      that human GSD-Ia would be treatable by gene therapy.

PMID- 12189169
TI  - Characterization of a major modifier locus for polycystic kidney disease
      (Modpkdr1) in the Han:SPRD(cy/+) rat in a region conserved with a mouse modifier
      locus for Alport syndrome.
AB  - The genetic analysis of rodent disease models provides a powerful tool to
      investigate how modifier loci cause variation in the phenotypic expression of a
      disease. In order to test the existence of modifier loci influencing polycystic
      kidney disease (PKD) phenotypes, we derived a backcross between PKD susceptible
      Han:SPRD(cy/+) and control Brown Norway (BN) rats, and performed a whole-genome
      scan in 182 PKD affected hybrids showing different grades of disease severity.
      The genetic dissection of PKD in the cross allowed us to detect a modifier locus,
      Modpkdr1, on rat chromosome 8 that controls PKD severity, kidney mass and plasma
      urea concentration. Results from database searches and computational analyses
      demonstrated that the Modpkdr1 locus shows strong evidence of synteny
      conservation with human and mouse chromosomal regions controlling kidney
      diseases, including disease progression of Alport syndrome. Comparative genome
      mapping also provided an inventory of potential candidate genes for modifier(s)
      of PKD. Analyses of the coding regions for four strong candidates (Ctsh, Bcl2a1,
      Trpc1 and Slc21a2) in (cy/+), BN and Lewis rat strains did not reveal sequence
      variants that could be associated with PKD. The characterization of Modpkdr1 may
      provide new insights into modulating mechanisms involved in the pathogenesis of
      PKD that could delay disease progression in humans. It may also have strong
      implications in the identification of pathophysiological factors common to
      different renal disorders.

PMID- 12189170
TI  - The GAA triplet-repeat sequence in Friedreich ataxia shows a high level of
      somatic instability in vivo, with a significant predilection for large
      contractions.
AB  - Friedreich ataxia is commonly caused by large expansions of a GAA triplet-repeat
      (GAA-TR) sequence in the first intron of the FRDA gene. We used small-pool PCR to
      analyze somatic variability among 7190 individual FRDA molecules from peripheral
      blood DNA of subjects carrying 12 different expanded alleles, ranging in size
      from 241 to 1105 triplets. Expanded alleles showed a length-dependent increase in
      somatic variability, with mutation loads ranging from 47% to 78%. We noted a
      strong contraction bias among long alleles (>500 triplets), which showed a 4-fold
      higher frequency of large contractions versus expansions. Some contractions were
      very large; of all somatic mutations scored, approximately 5% involved
      contractions of >50% of the original allele length, and 0.29% involved complete
      reversion to the normal/premutation length (< or =60 triplets). These
      observations contrast sharply with the strong expansion bias seen in expanded CTG
      triplet repeats in myotonic dystrophy. No somatic variability was detected in
      >6000 individual FRDA molecules analyzed from 15 normal alleles (8-25 triplets).
      A premutation allele with 44 uninterrupted GAA repeats was found to be unstable,
      ranging in size from 6 to 113 triplets, thus establishing the threshold for
      somatic instability between 26 and 44 GAA triplets. Analysis of an additional
      7850 FRDA molecules from serially passaged lymphoblastoid cell lines carrying
      nine expanded alleles (132-933 triplets) showed very low mutation loads, ranging
      from 0% to 6.2%. Our data indicate that expanded GAA-TR alleles in Friedreich
      ataxia are highly mutable and have a natural tendency to contract in vivo, and
      that these properties depend on multiple factors, including DNA sequence, triplet
      repeat length and unknown cell-type-specific factors.

PMID- 12189171
TI  - Defects in homologous recombination repair in mismatch-repair-deficient tumour
      cell lines.
AB  - Loss of mismatch repair (MMR) leads to a complex mutator phenotype that appears
      to drive the development of a subset of colon cancers. Here we show that MMR
      deficient tumour cell lines are highly sensitive to the toxic effects of
      thymidine relative to MMR-proficient lines. This sensitivity was not a direct
      consequence of MMR deficiency or alterations of DNA precursor metabolism.
      Instead, MMR-defective tumour cell lines are also defective in homologous
      recombination repair (HRR) induced by DNA double-strand breaks. Furthermore, a
      frameshift mutation of the human RAD51 paralog XRCC2 found in the MMR-deficient
      uterine tumour cell line SKUT-1 can confer thymidine sensitivity when introduced
      into a MMR-proficient line. Like other cells with defective XRCC2, SKUT-1 is
      sensitive to mitomycin C, and MMR-proficient cells expressing the mutant XRCC2
      allele become more sensitive to this agent. These data suggest that the thymidine
      sensitivity of MMR-deficient tumour cell lines may be a consequence of defects in
      the HRR pathway. The increased thymidine sensitivity and the loss of an important
      pathway for the repair of DNA double-strand breaks create new opportunities for
      therapies directed specifically against this subset of tumours.

PMID- 12189172
TI  - Rapid translocation of NTF2 through the nuclear pore of isolated nuclei and
      nuclear envelopes.
AB  - The mechanism by which macromolecules are translocated through the nuclear pore
      complex (NPC) is little understood. However, recent measurements of nuclear
      transport in permeabilized cells showed that molecules binding to phenylalanine
      glycine-rich repeats (FG repeats) in NPC proteins were translocated much faster
      through the NPC than molecules not interacting with FG repeats. We have studied
      that substrate preference of the NPC in isolated oocyte nuclei and purified
      nuclear envelopes by optical single transporter recording. NTF2, the transport
      receptor of RanGDP, was exported approximately 30 times faster than green
      fluorescent protein, an inert molecule of approximately the same size. The data
      confirm that restricted diffusion of inert molecules and facilitated transport of
      FG-repeat binding proteins are basic types of translocation through the NPC,
      demonstrating that the functional integrity of the NPC can be conserved in
      isolated nuclei and nuclear envelopes and thus opening new avenues to the
      analysis of nucleocytoplasmic transport.

PMID- 12189173
TI  - The ribosomal translocase homologue Snu114p is involved in unwinding U4/U6 RNA
      during activation of the spliceosome.
AB  - Snu114p is a yeast U5 snRNP protein homologous to the ribosomal elongation factor
      EF-2. Snu114p exhibits the same domain structure as EF-2, including the G-domain,
      but with an additional N-terminal domain. To test whether Snu114p in the
      spliceosome is involved in rearranging RNA secondary structures (by analogy to EF
      2 in the ribosome), we created conditionally lethal mutants. Deletion of this N
      terminal domain (snu114 Delta N) leads to a temperature-sensitive phenotype at 37
      degrees C and a pre-mRNA splicing defect in vivo. Heat treatment of snu114 Delta
      N extracts blocked splicing in vitro before the first step. The snu114 Delta N
      still associates with the tri-snRNP, and the stability of this particle is not
      significantly impaired by thermal inactivation. Heat treatment of snu114 Delta N
      extracts resulted in accumulation of arrested spliceosomes in which the U4 RNA
      was not efficiently released, and we show that U4 is still base paired with the
      U6 RNA. This suggests that Snu114p is involved, directly or indirectly, in the
      U4/U6 unwinding, an essential step towards spliceosome activation.

PMID- 12189174
TI  - A novel function for the U2AF 65 splicing factor in promoting pre-mRNA 3'-end
      processing.
AB  - Splicing and 3'-end processing (including cleavage and polyadenylation) of
      vertebrate pre-mRNAs are tightly coupled events that contribute to the extensive
      molecular network that coordinates gene expression. Sequences within the terminal
      intron of genes are essential to stimulate pre-mRNA 3'-end processing, although
      the factors mediating this effect are unknown. Here, we show that the pyrimidine
      tract of the last splice acceptor site of the human beta-globin gene is necessary
      to stimulate mRNA 3'-end formation in vivo and binds the U2AF 65 splicing factor.
      Naturally occurring beta-thalassaemia-causing mutations within the pyrimidine
      tract reduces both U2AF 65 binding and 3'-end cleavage efficiency. Significantly,
      a fusion protein containing U2AF 65, when tethered upstream of a
      cleavage/polyadenylation site, increases 3'-end cleavage efficiency in vitro and
      in vivo. Therefore, we propose that U2AF 65 promotes 3'-end processing, which
      contributes to 3'-terminal exon definition.

PMID- 12189175
TI  - Functional human CFTR produced by a stable minichromosome.
AB  - Artificial chromosomes have been claimed to be the ideal vector for gene therapy,
      but their use has been hampered by an inability to produce stable and well
      designed molecules. We have used a structurally defined minichromosome to clone
      the human cystic fybrosis transmembrane conductance regulator (CFTR) locus. To
      guarantee the presence of the proper regulatory elements, we used the 320 kb
      yeast artificial chromosome (YAC) 37AB12 with the intact CFTR gene and upstream
      sequences. The resulting minichromosome was analyzed for the presence of the
      entire CFTR gene and for its functional activity by molecular and functional
      methods. We have identified clones showing the presence of both the transcript
      and the CFTR protein. Moreover, in the same clones, a chloride secretory response
      to cAMP was detected. Mitotic and molecular stability after prolonged growth
      without selection demonstrated that the constructs were stable. This is the first
      example of a structurally known minichromosome made to contain an active
      therapeutic gene.

PMID- 12189176
TI  - Targeted disruption of hsp70.1 sensitizes to osmotic stress.
AB  - The 70 kDa heat shock protein (Hsp70) plays a critical role in cell survival and
      thermotolerance in response to various stress stimuli. Two nearly identical
      genes, hsp70.1 and hsp70.3, in response to environmental stress, rapidly induce
      Hsp70. However, it remains unclear whether these two genes are differentially
      regulated by various stresses. To address the physiological role of the hsp70.1
      and hsp70.3 genes in the stress response, we generated mice that specifically
      lack hsp70.1. In contrast to heat shock, which rapidly induced both hsp70.1 and
      hsp70.3 mRNA, osmotic stress selectively induced transcription of hsp70.1. In
      hsp70.1-deficient embryonic fibroblasts, osmotic stress markedly reduced cell
      viability. Furthermore, when osmotic stress was applied in vivo, hsp70.1
      deficient mice exhibited increased apoptosis in the renal medulla. Taken
      together, our results demonstrate that differential expression of hsp70 genes
      contributes to the stress response and that the hsp70.1 gene plays a critical
      role in osmotolerance.

PMID- 12189177
TI  - Bacteriophage-encoded cochaperonins can substitute for Escherichia coli's
      essential GroES protein.
AB  - The Escherichia coli chaperonin machine is composed of two members, GroEL and
      GroES. The GroEL chaperonin can bind 10-15% of E. coli's unfolded proteins in one
      of its central cavities and help them fold in cooperation with the GroES
      cochaperonin. Both proteins are absolutely essential for bacterial growth.
      Several large, lytic bacteriophages, such as T4 and RB49, use the host-encoded
      GroEL in conjunction with their own bacteriophage-encoded cochaperonin for the
      correct assembly of their major capsid protein, suggesting a cochaperonin
      specificity for the in vivo folding of certain substrates. Here, we demonstrate
      that, when the cochaperonin of either bacteriophage T4 (Gp31) or RB49 (CocO) is
      expressed in E. coli, the otherwise essential groES gene can be deleted. Thus, it
      appears that, despite very little sequence identity with groES, the bacteriophage
      encoded Gp31 and CocO proteins are capable of replacing GroES in the folding of
      E. coli's essential, housekeeping proteins.

PMID- 12189178
TI  - Conversion of omnipotent translation termination factor eRF1 into ciliate-like
      UGA-only unipotent eRF1.
AB  - In eukaryotic ribosomes, termination of translation is triggered by class 1
      polypeptide release factor, eRF1. In organisms with a universal code, eRF1
      responds to three stop codons, whereas, in ciliates with variant codes, only one
      or two codon(s) remain(s) as stop signals. By mutagenesis of the Y-C-F minidomain
      of the N domain, we converted an omnipotent human eRF1 recognizing all three stop
      codons into a unipotent 'ciliate-like' UGA-only eRF1. The conserved Cys127
      located in the Y-C-F minidomain plays a critical role in stop codon recognition.
      The UGA-only response has also been achieved by concomitant substitutions of four
      other amino acids located at the Y-C-F and NIKS minidomains of eRF1. We suggest
      that for eRF1 the stop codon decoding is of a non-linear (non-protein-anticodon)
      type and explores a combination of positive and negative determinants. We assume
      that stop codon recognition is profoundly different by eukaryotic and prokaryotic
      class 1 RFs.

PMID- 12189179
TI  - Factors affecting the direct targeting of murine leukemia virus vectors
      containing peptide ligands in the envelope protein.
AB  - To develop a reliable strategy for cell-specific delivery of retroviral vectors,
      we genetically modified the envelope (Env) protein of the ecotropic Moloney
      murine leukemia virus. We found a site in the variable region A, where the
      insertion of ligands, epidermal growth factor (EGF) and stromal-derived factor-1
      alpha (SDF-1 alpha), was possible without abolishing virion incorporation of the
      Env protein and its ecotropic entry function. The vector containing the EGF-Env
      did not show the EGF receptor-dependent transduction. The vector containing the
      SDF-1 alpha-Env, however, specifically transduced human cells expressing CXCR4,
      the receptor for SDF-1 alpha, at titers of 10(3)-10(4) c.f.u./ml. Further
      experiments showed that the CXCR4-dependent transduction was based on the
      specific interaction between the SDF-1 alpha moiety of the SDF-1 alpha-Env and
      CXCR4 and was independent of the ecotropic entry function. The direct targeting
      of the retroviral vector may be possible if the proper chimeric Env structure and
      the appropriate ligand-receptor system are employed.

PMID- 12189181
TI  - Sensitizing effects of cadmium on TNF-alpha- and TRAIL-mediated apoptosis of
      NIH3T3 cells with distinct expression patterns of p53.
AB  - Tumor necrosis factor (TNF)-alpha and TNF-related apoptosis inducing ligand
      (TRAIL) share a common signaling pathway. Here we show a novel potentiating
      effect of cadmium on TNF-alpha- or TRAIL-mediated cell death via distinct
      signaling. TNF-alpha or TRAIL sensitized otherwise resistant NIH3T3 embryo
      fibroblast cells to death, when exposed to cadmium. The potentiating effects
      elicited by TNF-alpha or TRAIL on cell death were NF-kappaB- and SAPK/JNK
      independent and were not diminished by the expression of Bcl-2. TNF-alpha
      potentiated the cadmium-induced accumulation of p53 but did not affect expression
      levels of Bax, Mdm2 and p21(WAF/CIP). A similar pattern of p53 accumulation was
      also observed in Balbc/3T3 fibroblasts but not in human tumor cell lines, MCF7
      and HeLa cells. The synergistic cell death evoked by TNF-alpha and cadmium was
      attenuated by transient expression of a dominant negative p53(Val135) mutant in
      NIH3T3 cells and was not observed in p53(-/-) mouse embryo fibroblasts,
      indicating that p53 accumulation appears to contribute to cell death. In
      contrast, TRAIL did not further increase the cadmium-induced accumulation of p53
      despite its potentiation effects on the cadmium-induced cell death. Expression of
      p53(Val135) mutant did not reduce TRAIL- and cadmium-mediated cell death. Taken
      together, these results suggest that TNF-alpha and TRAIL potentiate the cadmium
      mediated cell death via distinct p53 expression patterns.

PMID- 12189182
TI  - Induction of DNA polymerase beta-dependent base excision repair in response to
      oxidative stress in vivo.
AB  - Base excision repair (BER) is the DNA repair pathway primarily responsible for
      repairing small base modifications and abasic sites caused by normal cellular
      metabolism or environmental insult. Strong evidence supports the requirement of
      DNA polymerase beta (beta-pol) in the BER pathway involving single nucleotide gap
      filling DNA synthesis in mammalian systems. In this study, we examine the
      relationship between oxidative stress, cellular levels of beta-pol and BER to
      determine whether oxidizing agents can upregulate BER capacity in vivo.
      Intraperitoneal injection of 2-nitropropane (2-NP, 100 mg/kg), an oxidative
      stress-inducing agent, in C57BL/6 mice was found to generate 8
      hydroxydeoxyguanosine (8-OHdG) in liver tissue (4-fold increase, P < 0.001). We
      also observed a 4-5-fold increase in levels of DNA single strand breaks in 2-NP
      treated animals. The protein level of the tumor suppressor gene, p53 was also
      induced in liver by 2-NP (2.1-fold, P < 0.01), indicating an induction of DNA
      damage. In addition, we observed a 2-3-fold increase in mutant frequency in the
      lacI gene after exposure to 2-NP. Interestingly, an increase in DNA damage
      upregulated the level of beta-pol as well as BER capacity (42%, P < 0.05). These
      results suggest that beta-pol and BER can be upregulated in response to oxidative
      stress in vivo. Furthermore, data show that heterozygous beta-pol knockout (beta
      pol(+/-)) mice express higher levels of p53 in response to 2-NP as compared with
      wild-type littermates. While the knockout and wild-type mice display similar
      levels of 8-OHdG after 2-NP exposure, the beta-pol(+/-) mice exhibit a
      significant increase in DNA single strand breaks. These findings suggest that in
      mice, a reduction in beta-pol expression results in a higher accumulation of DNA
      damage by 2-NP, thus establishing the importance of the beta-pol-dependent BER
      pathway in repairing oxidative damage.

PMID- 12189180
TI  - Reverse genetics in the mosquito Anopheles gambiae: targeted disruption of the
      Defensin gene.
AB  - Anopheles gambiae, the major vector of human malaria parasite, is an important
      insect model to study vector-parasite interactions. Here, we developed a simple
      in vivo double-stranded RNA (dsRNA) knockout approach to determine the function
      of the mosquito antimicrobial peptide gene Defensin. We injected dsRNA into
      adults and observed efficient and reproducible silencing of Defensin. Analysis of
      the knockdown phenotype revealed that this peptide is required for the mosquito
      antimicrobial defense against Gram-positive bacteria. In contrast, in mosquitoes
      infected by Plasmodium berghei, no loss of mosquito viability and no significant
      effect on the development and morphology of the parasite midgut stages were
      observed in the absence of Defensin. We conclude that this peptide is not a major
      antiparasitic factor in A. gambiae in vivo. Our results open new perspectives for
      the study of mosquito gene function in vivo and provide a basis for genome-scale
      systematic functional screens by targeted gene silencing.

PMID- 12189183
TI  - Frequency of Tk and Hprt lymphocyte mutants and bone marrow micronuclei in
      B6C3F(1)/Tk+/- mice treated neonatally with zidovudine and lamivudine.
AB  - Mother-to-child transmission of the human immunodeficiency virus is substantially
      reduced by prenatal and postnatal treatment with anti-retroviral nucleoside
      analogues; however, the long-term consequences of these drug interventions are
      not known. The nucleoside analogue zidovudine (3'-azido-2',3'-dideoxythymidine;
      AZT) is carcinogenic in mice when administered transplacentally or neonatally,
      and this may be due to a genotoxic mechanism. Since single-drug treatment with
      AZT is being superseded by multidrug combinations, we have investigated the
      induction of mutations and micronuclei in mice treated neonatally with AZT,
      lamivudine (3'-thia-2',3'-dideoxycytidine; 3TC), or a combination of the two
      drugs. B6C3F(1)/Tk+/- mice were treated daily from days 1-8 of age with 200 mg
      AZT/kg/day, 200 mg 3TC/kg/day, or a mixture of 200 mg AZT + 200 mg 3TC/kg/day
      (AZT/3TC). One and 2 days after the last dose, bone marrow was collected to
      assess the induction of micronuclei in polychromatic erythrocytes; 3 weeks
      following treatment, the induction of mutants was determined in the hypoxanthine
      guanine phosphoribosyltransferase (Hprt) and thymidine kinase (Tk) genes of
      spleen lymphocytes. AZT and AZT/3TC, but not 3TC, caused a significant increase
      in micronuclei, with the response being greatest one day after the last dose.
      None of the drugs induced mutations in the Hprt gene, while AZT and AZT/3TC, but
      not 3TC, caused a significant increase in the Tk mutant frequency. The increase
      in Tk mutants by AZT and AZT/3TC was associated with loss of the wild-type (Tk+)
      allele (loss of heterozygosity). These data suggest that AZT, but not 3TC, is
      genotoxic in neonatal mice, and that 3TC does not alter significantly the
      responses observed with AZT alone.

PMID- 12189184
TI  - Effects of benzyl isothiocyanate and phenethyl isothiocyanate on DNA adduct
      formation by a mixture of benzo[a]pyrene and 4-(methylnitrosamino)-1-(3-pyridyl)
      1-butanone in A/J mouse lung.
AB  - Dietary phenethyl isothiocyanate (PEITC) and a mixture of dietary PEITC and
      benzyl isothiocyanate (BITC) inhibit lung tumorigenesis in A/J mice induced by a
      mixture of the tobacco smoke carcinogens benzo[a]pyrene (B[a]P) and 4
      (methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK). In this study, we tested the
      hypothesis that inhibition of tumorigenesis by these isothiocyanates was due to
      inhibition of DNA adduct formation. We quantified the following pulmonary DNA
      adducts: N2-[7,8,9-trihydroxy-7,8,9,10-tetrahydrobenzo[a]pyrene-10
      yl]deoxyguanosine (BPDE-N2-dG) from B[a]P; and O(6)-methylguanine (O(6)-mG) and 4
      hydroxy-1-(3-pyridyl)-1-butanone (HPB)-releasing adducts from NNK. Initial
      experiments demonstrated that there were no effects of B[a]P on NNK-DNA adduct
      formation, or vice versa, and established by way of a time course study the
      appropriate sacrifice intervals for the main experiment. Dietary PEITC, or
      dietary BITC plus PEITC, inhibited the formation of HPB-releasing DNA adducts of
      NNK at several of the time points examined. There were no effects of dietary
      isothiocyanates on levels of O(6)-mG or BPDE-N2-dG. These results, which are
      consistent with previous studies in rats and with tumor inhibition data in mice,
      support a role for inhibition of HPB-releasing DNA adducts of NNK as a mechanism
      of inhibition of tumorigenesis by dietary PEITC and BITC plus PEITC. However, the
      observed inhibition was modest, suggesting that other effects of isothiocyanates
      are also involved in chemoprevention in this model.

PMID- 12189185
TI  - Oxidative stress in humans: validation of biomarkers of DNA damage.
AB  - Two studies have been performed to clarify the relationship between different
      markers of oxidative DNA damage commonly employed in molecular epidemiological
      studies. In the first, 8-Oxo-7,8-dihydroguanine (8-oxoGua) was induced in DNA of
      HeLa cells by treatment with different concentrations of photosensitizer Ro 19
      8022 together with visible light. 8-OxoGua was estimated by the comet assay
      (alkaline single cell gel electrophoresis) with formamidopyrimidine DNA
      glycosylase and by HPLC with electrochemical detection. The dose-response curves
      indicate that the comet assay and HPLC are equally efficient at detecting induced
      damage. Background levels of 8-oxoGua in HeLa cells were 0.92 +/- 0.22 per 10(6)
      guanines by the comet assay and 2.09 +/- 0.13 per 10(6) guanines by HPLC. The
      second study was a small human trial, in which lymphocytes were collected for
      analysis of background levels of 8-oxoGua, as well as overnight and 24 h urine
      samples for measurement of excreted 8-oxo-7,8-dihydro-2'-deoxyguanosine (8
      oxodGuo) by ELISA. The mean level of 8-oxoGua in lymphocytes was determined as
      1.33 +/- 0.21 per 10(6) guanines by the comet assay and 3.72 +/- 1.06 per 10(6)
      guanines by HPLC. A strong correlation was seen between overnight and 24 h
      urinary 8-oxodGuo (r = 0.93, P < 0.01). Overnight urinary 8-oxodGuo
      concentrations correlated with 8-oxoGua in lymphocytes measured by HPLC (r =
      0.85, P < 0.05) or by the comet assay (r = 0.86, P < 0.05), although individual
      values from HPLC and the comet assay did not correlate with each other. It is
      reasonable to assess oxidative stress by any of these methods.

PMID- 12189186
TI  - Altered expression of c-myc, p16 and p27 in rat colon tumors and its reversal by
      short-term treatment with chemopreventive agents.
AB  - Modulation of gene expression in tumors has the potential of being a surrogate
      end-point biomarker for chemoprevention. Thus, we determined the modulation by
      chemopreventive agents of the protein and mRNA expression of genes in rat colon
      tumors. Male F344 rats were administered three weekly injections of 15 mg/kg
      azoxymethane. Forty-seven weeks later, they received aspirin (600), calcium
      chloride (50 000), 2-(carboxyphenyl) retinamide (2-CPR, 315), alpha
      difluoromethylornithine (DFMO, 3000), piroxicam (200), quercetin (33 600), 9-cis
      retinoic acid (9-cis RA, 30), rutin (3000), or sulindac (280) in their diet at
      the indicated mg/kg concentration for 7 days and were then killed. In colon
      tumors relative to the mucosa, the protein and mRNA levels of c-myc were
      increased, while the levels of p16 and p27 were decreased. Calcium chloride,
      DFMO, piroxicam and sulindac administered for 7 days decreased the mitotic index
      and reduced the protein and mRNA levels of c-myc in colon tumors. Calcium
      chloride, DFMO and piroxicam increased the protein and mRNA levels of p16 and
      along with sulindac increased the protein level of p27, but not its mRNA. The
      other agents failed to modulate both the mitotic index and the expression of the
      genes. The ability of the chemopreventive agents to prevent colon tumors was
      determined. Male F344 rats were administered three weekly injections of 15 mg/kg
      azoxymethane and 8 weeks later they were administered aspirin, 2-CPR, DFMO,
      piroxicam, 9-cis RA and rutin in their diet. The rats were killed 26 weeks after
      they started to receive the chemopreventive agents. The multiplicity of colon
      tumors was reduced by DFMO and piroxicam, increased by rutin and not affected by
      the other agents. Hence, agents that prevented colon cancer decreased the mitotic
      index and altered the expression of c-myc, p16 and p27 suggesting that modulation
      in the expression of these genes are potential biomarkers for chemopreventive
      activity.

PMID- 12189187
TI  - Inhibition of lung tumorigenesis in A/J mice by N-acetyl-S-(N-2
      phenethylthiocarbamoyl)-L-cysteine and myo-inositol, individually and in
      combination.
AB  - Isothiocyanates, their N-acetylcysteine conjugates, and myo-inositol (MI) are
      inhibitors of lung tumorigenesis in A/J mice. However, chemoprevention by
      combinations of these compounds in different temporal sequences has not been
      examined. This is important for developing practical approaches to lung cancer
      chemoprevention in smokers and ex-smokers. We used a tumor model in which A/J
      mice are treated with 8 weekly doses of benzo[a]pyrene (B[a]P) plus 4
      (methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) and killed 19 weeks after the
      final treatment. In Experiment 1, isothiocyanates or their N-acetylcysteine
      conjugates were added to the diet (1 or 3 micro mol/g) from 1 week before until 1
      week after carcinogen treatment. The compounds were 2-phenethyl isothiocyanate
      (PEITC), 3-phenylpropyl isothiocyanate (PPITC), N-acetyl-S-(N-benzyl
      thiocarbamoyl)-L-cysteine (BITC-NAC), N-acetyl-S-(N-2-phenethylthiocarbamoyl)-L
      cysteine (PEITC-NAC), and N-acetyl-S-(N-3-phenylpropylthiocarbamoyl)-L-cysteine
      (PPITC-NAC). Significant reductions in lung tumor multiplicity were observed in
      mice treated with PEITC, PEITC-NAC, PPITC and PPITC-NAC. PEITC-NAC was chosen for
      combination studies with MI (Experiment 2). Mice were treated with B[a]P plus NNK
      without or with PEITC-NAC (3 micro mol/g diet), MI (55.5 micro mol/g diet), or
      PEITC-NAC plus MI (3 micro mol plus 55.5 micro mol/g diet). Different temporal
      sequences of dietary additions were investigated: carcinogen treatment phase;
      post-carcinogen treatment phase; entire experiment; 50% of carcinogen treatment
      phase until termination; and 75% of carcinogen treatment phase until termination.
      All treatments reduced lung tumor multiplicity except PEITC-NAC post-carcinogen
      or from 75% of the carcinogen treatment phase. Reduction of lung tumor
      multiplicity by PEITC-NAC plus MI was greater than that in the mice treated with
      the agents alone in all temporal sequences. When all results were combined, PEITC
      NAC plus MI was significantly more effective than the agents alone. There was a
      significant trend for reduction in lung tumor multiplicity with increased
      duration of treatment by the chemopreventive agents. These results provide a
      basis for further development of mixtures of PEITC-NAC and MI for chemoprevention
      of lung cancer.

PMID- 12189188
TI  - Inhibitory effects of mofezolac, a cyclooxygenase-1 selective inhibitor, on
      intestinal carcinogenesis.
AB  - Cyclooxygenase (COX)-2, one enzyme isoform responsible for producing prostanoids
      from arachidonic acid, contributes to colon carcinogenesis. Recently, genetic
      disruption of COX-1, the other isoform, was shown to decrease the number of
      intestinal polyps and prostaglandin E(2) levels in intestinal mucosa, like the
      case with COX-2 gene disruption, in Min mice. We therefore investigated whether a
      COX-1 selective inhibitor, mofezolac, suppresses intestinal carcinogenesis in
      rodents. F344 male rats, receiving azoxymethane (AOM, 15 mg/kg body wt) s.c.
      injections at 5 and 6 weeks of age, were fed a diet containing 600 or 1200 p.p.m.
      mofezolac for 4 weeks. The number of aberrant crypt foci (ACFs) per rat and the
      bromodeoxyuridine labeling index of the crypt epithelium were dose-dependently
      decreased by administration of mofezolac, the value for the former at 1200 p.p.m.
      being 60% of control value. When Apc gene knockout mice (APC1309 mice) were given
      600 or 1200 p.p.m. mofezolac in their diet for 8 weeks, the numbers of intestinal
      polyps were also dose-dependently decreased, with reduction to 59% of that in the
      control diet group at the higher dose. Nimesulide, a COX-2 selective inhibitor
      used as positive control, showed similar suppressive effects on the development
      of ACFs in AOM-treated rats and polyps in Apc gene knockout mice. The data
      indicate that both COX-1 and COX-2 can contribute to intestinal tumorigenesis.

PMID- 12189190
TI  - Genetic polymorphisms of glutathione S-transferases as modulators of lung cancer
      susceptibility.
AB  - Some of the glutathione S-transferases (GSTs) are polymorphic and may play a role
      in lung cancer susceptibility. Our previous study in a French Caucasian study
      population suggested GSTM1 null genotype as a moderate risk factor for lung
      cancer. Here we extended the study to investigate the potential role of GSTT1 and
      GSTP1 polymorphisms in susceptibility to lung cancer, either separately or in
      combination. The study population consisted of 268 controls and 251 cases.
      Nineteen percent of the controls and 15% of the cases had GSTT1 null genotype.
      The distribution of GSTP1*A/*A, *A/*B and *B/*B genotypes were 46.9, 45.5 and
      7.6% in controls, and 47.8, 40.2 and 12.0% in cases, respectively. No
      statistically significant effects in the lung cancer risk were observed for the
      GSTT1 genotypes, but the GSTP1*B/*B genotype posed a 2-fold risk [odds ratio (OR)
      = 2.0, 95% confidence interval (CI) 1.0-4.1] of this malignancy compared with the
      GSTP1*A allele containing genotypes; this association was mainly attributable to
      small cell lung cancer (OR = 3.6, 95% CI 1.3-9.8). The most remarkable risk was
      seen for the small cell carcinoma among subjects with the GSTP1*B/*B genotype and
      concurrent lack of the GSTM1 gene (OR = 6.9, 95% CI 1.6-30.2). The deficient
      genotypes for GSTM1 and GSTP1 seem thus to be important risk modifiers for lung
      cancer, especially in combination.

PMID- 12189189
TI  - Genistein action in the prepubertal mammary gland in a chemoprevention model.
AB  - A diet high in soy is associated with many health benefits, including reduced
      incidence of breast cancer. The soy phytoestrogen, genistein, is hypothesized to
      contribute to mammary chemoprevention via interaction with estrogen receptors
      (ERs) alpha and/or beta. These steroid signaling pathways are believed to exert
      control over proliferation and differentiation of the mammary gland by a complex
      bidirectional interaction with the epidermal growth factor (EGF) signaling
      pathway. The current work was designed to study the role of these two pathways in
      prepubertal mammary gland growth. Female Sprague-Dawley CD rats were injected
      with genistein (500 micro g/g body wt) or estradiol benzoate (EB) (500 ng/g body
      wt) on days 16, 18 and 20. Whole mount analysis of mammary glands from 21-day-old
      rats showed that both treatments resulted in significantly increased terminal end
      buds (TEBs), and increased ductal branching, compared with animals given the
      vehicle, dimethylsulfoxide (DMSO). Both effects were inhibited by blockage of ER
      function by pre-treating with 2 mg ICI 182,780/kg body wt, a steroidal anti
      estrogen. Immunoblotting analyis of mammary gland extracts demonstrated increased
      epidermal growth factor receptor (EGFR) and progesterone receptor (PR) expression
      following treatment with EB or genistein. Tyrosine-phosphorylated EGFR, as
      measured by immunoprecipitation/immunoblotting was also increased, but when
      normalized to total receptors, there was no net effect. The expression and
      phosphorylation of downstream targets of the EGFR, mitogen activating kinase
      kinase (MEK 1 and 2) and extracellular signal regulated kinases 1 and 2 (ERK 1
      and 2) were not significantly affected. Anti-estrogen pre-treatment prevented the
      increase in EGFR, phospho-EGFR and PR. The data indicate an ER-based mechanism of
      action for genistein in mammary gland proliferation and differentiation, which
      can lead to protection against mammary cancer.

PMID- 12189191
TI  - Nutritional and lifestyle determinants of DNA oxidative damage: a study in a
      Mediterranean population.
AB  - In order to evaluate dietary and lifestyle determinants of oxidative DNA damage
      we used a modification of the 'comet assay' (single cell alkaline gel
      electrophoresis), with the fpg enzyme (formamidopyrimidine DNA glycosilase), to
      measure the basal level of DNA oxidation in peripheral lymphocytes donated by 71
      healthy adults living in Florence, Italy. Detailed information about dietary and
      lifestyle habits was collected by two validated and standardized questionnaires;
      we also measured plasma concentrations of selected micro-nutrients (six
      carotenoids, retinol, alpha- and gamma-tocopherol). DNA damage, measured as
      percent DNA migrated in the comet tail (mean 4.67%, interquartile range 2.36
      6.62%), was not associated with gender, age, weight, body mass index, physical
      activity or smoking history. A positive correlation with height and period of
      blood sampling emerged: DNA damage tended to be higher among taller subjects (P =
      0.02) and in samples obtained in summer months (P = 0.02). Multivariate analyses
      showed a positive association with coffee (P = 0.01) and tomato consumption (P =
      0.05). Instead, the consumption of cruciferous vegetables tended to be negatively
      associated with oxidative damage (P = 0.09). Furthermore, a positive non
      significant association between the consumption of total vegetables and fresh
      fruit and DNA damage emerged (P = 0.08 and P = 0.10, respectively). The estimated
      intake of simple sugars showed a strong positive association with oxidative DNA
      damage (P = 0.01), while vitamin E showed a borderline positive association (P =
      0.06). The plasma levels of several micro-nutrients did not appear to influence
      DNA damage. Our results, although based on a relatively small group of subjects,
      indicate that individual dietary and lifestyle habits only modestly affect the
      levels of lymphocyte DNA oxidation and suggest that specific dietary patterns,
      rich in fresh fruit and vegetables, are not clearly related to decreased
      oxidative damage in peripheral lymphocytes in a Mediterranean population.

PMID- 12189192
TI  - Adolescent and adult soy intake and risk of breast cancer in Asian-Americans.
AB  - The association between soyfood intake and breast cancer risk is controversial.
      Most of the epidemiologic studies published on this topic in the 1990s were not
      designed to specifically address this question. We conducted a population-based,
      case-control study of breast cancer among Chinese, Japanese and Filipino women in
      Los Angeles County to further investigate the role of soy. Our primary objective
      was to quantify breast cancer risks associated with intake of soy during
      adolescence and adult life among Asian-American women. During 1995-1998, we
      successfully interviewed 501 breast cancer patients and 594 control subjects.
      Intake of soy among Asian-Americans is still relatively high; the median intake
      was 12 mg isoflavones/day, approximately one-third of that reported in a recent
      study in Shanghai, China. The risk of breast cancer was significantly inversely
      associated with soy intake during adolescence and adult life. After adjusting for
      age, specific Asian ethnicity, education, migration history and menstrual and
      reproductive factors, women who reported soy intake at least once per week during
      adolescence showed a statistically significantly reduced risk of breast cancer.
      There was also a significant trend of decreasing risk with increasing soy intake
      during adult life. When we considered soy intake during both adolescence and
      adult life, subjects who were high-soy consumers during both time periods showed
      the lowest risk (OR=0.53, 95% CI=0.36-0.78) compared with those who were low
      consumers during both time periods. Risk of breast cancer was intermediate among
      subjects who were high-soy consumers during adolescence and low-soy consumers
      during adult life (OR=0.77, 95% CI=0.51-1.10). Based on a relatively small number
      of subjects, the risk did not appear to differ between those who were low
      consumers during adolescence and high consumers during adult life. Results
      remained similar after adjustment for other potential confounders including other
      dietary and non-dietary risk factors for breast cancer. These results show that
      high soy intake in childhood in Asian-Americans is associated with reduced breast
      cancer risk. Risk may be further reduced by intake as an adult.

PMID- 12189193
TI  - Urinary tea polyphenols in relation to gastric and esophageal cancers: a
      prospective study of men in Shanghai, China.
AB  - Experimental studies have shown that tea and tea polyphenols have
      anticarcinogenic properties. There have been no prospective investigations
      examining the relationship between tea polyphenols and cancer risk using
      validated biomarkers. In the present study, a nested case-control study design
      was used to investigate the association between prediagnostic urinary tea
      polyphenol markers and subsequent risk of gastric and esophageal cancers. One
      hundred and ninety incident cases of gastric cancer and 42 cases of esophageal
      cancer occurring in members of the Shanghai Cohort (18 244 men aged 45-64 years
      at recruitment with up to 12 years of follow-up) were compared with 772 cohort
      control subjects. The control subjects were individually matched to the index
      cases by age, month and year of sample collection, and neighborhood of residence
      (case-control ratio = 1:3 for gastric cancer, 1:5 for esophageal cancer). Urinary
      tea polyphenols, including epigallocatechin (EGC) and epicatechin (EC), and their
      respective metabolites 5-(3',4',5'-trihydroxyphenyl)-gamma-valerolactone (M4) and
      5-(3',4'-dihydroxyphenyl)-gamma-valerolactone (M6), were measured in all study
      subjects by means of a validated assay. Odds ratios (ORs) and 95% confidence
      intervals (CIs) were calculated from logistic regression models. After exclusion
      of cases diagnosed under 4 years follow-up, urinary EGC positivity showed a
      statistically significant inverse association with gastric cancer (OR = 0.52, 95%
      CI = 0.28-0.97) after adjustment for Helicobactor pylori seropositivity, smoking,
      alcohol drinking, and level of serum carotenes. The protective effect was
      primarily seen among subjects with low (below population median) serum carotenes.
      The odds ratio for EGC positivity was 0.49 (95% CI = 0.26-0.94) among subjects
      with low serum carotenes while the corresponding odds ratio among subjects with
      higher levels of serum carotenes was 1.02 (95% CI = 0.46-2.28). Similar tea
      polyphenol-cancer risk associations were observed when the gastric cancer and
      esophageal cancer sites were combined. The present study provides direct evidence
      that tea polyphenols may act as chemopreventive agents against gastric and
      esophageal cancer development.

PMID- 12189194
TI  - Inter-individual variation, seasonal variation and close correlation of OGG1 and
      ERCC1 mRNA levels in full blood from healthy volunteers.
AB  - The mRNA levels of the nucleotide excision DNA repair gene ERCC1 and the base
      excision DNA repair gene OGG1 were quantified in 43 healthy volunteers in a
      dietary intervention trial as markers for the DNA repair capacity. Nine samples
      were collected from each subject over a period of 52 days. Sampling took place
      from January to May. The mRNA levels of OGG1 and ERCC1 correlated closely (r =
      0.86, P << 0.0001) after normalization to either 18S ribosomal RNA or to beta
      actin mRNA. The levels of OGG1 and ERCC1 mRNA were relatively constant within an
      individual with intra-individual correlation (R(2) = 0.45-0.46) in a General
      Linear Model. The amounts of ERCC1 and OGG1 relative to 18S RNA were doubled in
      May compared with January. This coincided with an increase in the monthly influx
      of sunlight from 18 MJ/m(2) in January to 242 MJ/m(2) in May. The mRNA levels of
      both ERCC1 and OGG1 were positively correlated to the average daily influx of
      sunlight in the previous 30 and 5 days (r = 0.49; r = 0.37, respectively, P <<
      0.001). There were no significant effects of the dietary interventions. The inter
      individual variation was 5-10-fold, which is more than the observed 2-3-fold
      seasonal variation. Thus, despite seasonal variation of the individual mRNA
      levels, the inter-person variation is still far larger than the intra-person
      variation, supporting the use as biomarkers.

PMID- 12189195
TI  - Cigarette smoke condensate activates nuclear transcription factor-kappaB through
      phosphorylation and degradation of IkappaB(alpha): correlation with induction of
      cyclooxygenase-2.
AB  - Cigarette smoke (CS) contains several carcinogens known to initiate and promote
      tumorigenesis and metastasis. Because various genes that mediate carcinogenesis
      and tumorigenesis are regulated by nuclear factor-kappaB (NF-kappaB), we
      postulated that the effects of CS must be mediated through activation of this
      transcription factor. Therefore, in the present report we investigated whether
      cigarette smoke condensate (CSC) activates NF-kappaB, and whether the pathway
      employed for activation is similar to that of TNF, one of the potent activators
      of NF-kappaB. Our results show that the treatment of human histiocytic lymphoma U
      937 cells with CSC activated NF-kappaB in a dose- and time-dependent manner. The
      kinetics of NF-kappaB activation by CSC was comparable with that of TNF. CSC
      induced NF-kappaB activation was not cell type-specific, as it also activated NF
      kappaB in T cells (Jurkat), lung cells (H1299), and head and neck squamous cell
      lines (1483 and 14B). Activation of NF-kappaB by CSC correlated with time
      dependent degradation of IkappaB(alpha), an inhibitor of NF-kappaB. Further
      studies revealed that CSC induced phosphorylation of the serine residue at
      position 32 in IkappaB(alpha). In vitro immunocomplex kinase assays showed that
      CSC activated IkappaB(alpha) kinase (IKK). The suppression of CSC-activated NF
      kappaB-dependent reporter gene expression by dominant negative form of
      IkappaB(alpha), TRAF2, NIK and IKK suggests a similarity to the TNF-induced
      pathway for NF-kappaB. CSC also induced the expression of cyclooxygenase-2, an NF
      kappaB regulated gene product. Overall, our results indicate that through
      phosphorylation and degradation of IkappaB(alpha), CSC can activate NF-kappaB in
      a wide a variety of cells, and this may play a role in CS-induced carcinogenesis.

PMID- 12189196
TI  - Induction of tumors in the colon and liver of the immunodeficient (SCID) mouse by
      2-amino-3-methylimidazo[4,5-f ]quinoline (IQ)-modulation by long-chain fatty
      acids.
AB  - We have recently shown that immunodeficient (SCID) mice, which lack functional T
      and B cells, are highly susceptible to low dose site specific induction of colon
      aberrant crypt foci (ACF), surrogates for colon tumors, by 2-amino-3
      methylimidazo[4,5-f ]quinoline (IQ). To test whether long-term exposure to a high
      dose in the diet might prove carcinogenic to the SCID mouse colon, in contrast to
      other mice strains tested to date, the compound was administered at 300 p.p.m. in
      the diet to female 6-7-week-old SCID mice for 32 weeks. IQ induced high numbers
      of ACF, hyperplastic polyps, dysplasia, and colon adenomas, as well as
      hepatocellular altered foci and liver adenomas. Induction of colon tumors did not
      correlate with the main sites where ACF developed, the proximal colon, however,
      being seen mainly in the mid and distal colon. Induction of colon tumors
      correlated significantly with the incidence of dysplasia, crypt height, the
      mitotic index, cell proliferation and numbers of 8-hydroxydeoxyguanosine (8-OHdG)
      positive cells in the colon crypt, particularly in mid and distal colon.
      Administration of 20% omega-6 polyunsaturated fatty acids (corn oil), omega-3
      polyunsaturated fatty acids (perilla oil), or monounsaturated fatty acids (olive
      oil) simultaneously with IQ in the diet resulted in: (i) inhibition of colon and
      liver tumor induction by corn and perilla oil, whereas olive oil showed no
      effects; (ii) no reduction in total numbers of ACF by corn oil or perilla oil but
      significant suppression in the olive oil treated group; (iii) inhibition of tumor
      development particularly by omega-3 polyunsaturated fatty acids in perilla oil,
      correlating significantly with decreased cell proliferation in both colon and
      liver and a marked decrease in crypt heights and mitotic indices. Selective
      reduction in the numbers of 8-OHdG-positive nuclei, mainly in the middle and
      distal colon crypts, was also found to correlate with tumor inhibition. Thus, the
      results indicate carcinogenicity of IQ in the colon of the SCID mouse and
      preventive effects of polyunsaturated fatty acids.

PMID- 12189197
TI  - Suppression of N-nitrosomethylbenzylamine (NMBA)-induced esophageal tumorigenesis
      in F344 rats by resveratrol.
AB  - Resveratrol (3,5,4'-trihydroxy-trans-stilbene) is a natural product occurring in
      grapes and various other plants with medicinal properties associated with reduced
      cardiovascular disease and reduced cancer risk. To evaluate the possibility and
      potential mechanism(s) of which resveratrol inhibits N-nitrosomethylbenzylamine
      (NMBA)-induced rat esophageal tumorigenesis, 96 F344 male rats were divided into
      10 groups and resveratrol (1 and 2 mg/kg) was administered orally or
      intraperitoneally (i.p.). In the groups in which resveratrol was administered at
      2 mg/kg (orally, for 16 weeks), 1 and 2 mg/kg (i.p., for 16 weeks) and 1 mg/kg
      (i.p., for 20 weeks), the number of NMBA-induced esophageal tumors per rat was
      significantly reduced to 78, 62, 54 and 48, respectively (P < 0.05), and the size
      of maximum tumors in each group with resveratrol treatment was also significantly
      smaller than that in NMBA alone group (P < 0.05). Although the pathological
      examination did not indicate significantly decreased incidence of carcinomas by
      administering resveratrol, the tendency of carcinogensis suppression was observed
      (P = 0.177). Semi-quantitative RT-PCR and ELISA analysis demonstrated that
      following NMBA treatment, the expression of COX-1 mRNA was strongly present in
      tumor tissues, while weakly present in non-tissues; the expression of COX-2 mRNA
      was induced in both tumor and non-tumor tissues. The production of prostaglandin
      E(2) (PGE(2)) increased approximately 6-fold, compared with the normal esophageal
      mucosa. The higher expression of COX-1, the up-regulated COX-2 expression and the
      increased levels of PGE(2) synthesis were all significantly decreased by
      administering resveratrol. Our study suggests that resveratrol suppressed NMBA
      induced rat esophageal tumorigenesis by targeting COXs and PGE(2), and therefore
      may be a promising natural anti-carcinogenesis agent for the prevention and
      treatment of human esophageal cancer.

PMID- 12189198
TI  - Mutation, DNA strand cleavage and nitric oxide formation caused by N
      nitrosoproline with sunlight: a possible mechanism of UVA carcinogenicity.
AB  - N-Nitrosoproline (NPRO) is endogenously formed from proline and nitrite. NPRO has
      been reported to be nonmutagenic and noncarcinogenic. In this study, we have
      detected the direct mutagenicity of NPRO plus natural sunlight towards Salmonella
      typhimurium. Furthermore, formation of 8-oxo-7,8-dihydro-2'-deoxyguanosine (8
      oxodG), a mutagenic lesion, was observed in calf thymus DNA treated with NPRO
      plus simulated sunlight. The treatment with NPRO and sunlight induced single
      strand breaks in the superhelical replicative form of phage M13mp2 DNA. Single
      strand DNA breaks also occurred in the human fibroblast cells on treatment with
      NPRO plus UVA, as detected by the comet assay. An analysis using scavengers
      suggested that both reactive oxygen species and NO radical mediate the strand
      breaks. The formation of nitric oxide was observed in NPRO solution irradiated
      with UVA. We analyzed the photodynamic spectrum of mutation induction and DNA
      breakage using monochromatic radiation at a series of wavelengths between 300 and
      400 nm. Both mutation frequencies and DNA breakage were highest at the absorption
      maximum of NPRO, 340 nm. The co-mutagenic and co-toxic actions of NPRO and
      sunlight merit attention as possible mechanisms increasing the carcinogenic risk
      from UVA irradiation.

PMID- 12189199
TI  - Elevated susceptibility of the p53 knockout mouse esophagus to methyl-N
      amylnitrosamine carcinogenesis.
AB  - Mutations of the p53 tumor suppressor gene constitute one of the most frequent
      molecular changes in a wide variety of human cancers, including those in the
      esophagus. Mice deficient in p53 have recently attracted attention for their
      potential to identify chemical genotoxins. In this study we investigated the
      susceptibility of p53 nullizygous (-/-), heterozygous (+/-) and wild-type (+/+)
      mice to methyl-N-amylnitrosamine (MNAN), which specifically induces esophageal
      tumors in mice and rats. The p53 (+/-) and (+/+) mice were treated with 5 or 15
      p.p.m. MNAN in their drinking water for 8 weeks then maintained without further
      treatment for an additional 7 or 17 weeks, being killed at experimental weeks 15
      or 25. An additional group of p53 (-/-) mice were given 5 p.p.m. MNAN for 8 weeks
      and killed at week 15. At 15 weeks in the 5 p.p.m. groups, squamous cell
      carcinomas (SCCs) were observed in 10/12 (83.3%) p53 (-/-) and 1/15 (6.7%) p53
      (+/-) mice, but in none of the p53 (+/+) mice. In the animals receiving 15
      p.p.m., 2/14 (14.3%) p53 (+/-) and 1/11 (9.1%) p53 (+/+) mice developed SCCs. At
      25 weeks, the incidence of SCCs was 7/16 (43.8%) and 8/14 (57.1%) in p53 (+/-)
      mice and 1/13 (7.7%) and 2/10 (20.0%) in p53 (+/+) mice at 5 and 15 p.p.m.,
      respectively. Of the SCCs examined by PCR-single strand conformation polymorphism
      analysis, 61% (14/23) from p53 (+/-) and 50% (6/12) from p53 (+/+) mice
      demonstrated mutations in the p53 gene (exons 5-8). These results indicate the
      order of susceptibility to MNAN-induced esophageal tumorigenesis to be as
      follows: nullizygotes (-/-) > heterozygotes (+/-) > wild-type (+/+), and provide
      strong evidence of involvement of p53 mutations in the development of esophageal
      SCCs.

PMID- 12189200
TI  - Promotion, but not progression, effects of tamoxifen on uterine carcinogenesis in
      mice initiated with N-ethyl-N'-nitro-N-nitrosoguanidine.
AB  - Effects of tamoxifen (TAM) on development of uterine endometrial carcinogenesis
      were studied in intact and ovariectomized (OVX) mice initiated with N-ethyl-N'
      nitro-N-nitrosoguanidine (ENNG). In experiment I, animals were implanted with
      cholesterol (ChL, controls) or TAM (5% w/w) and/or 17beta-oestradiol (E(2), 0.5%
      w/w) pellets s.c. from 9 to 25 weeks of age, until the termination of the
      experiment, and all received a single intra-uterine administration of ENNG (12.5
      mg/kg) at 10 weeks of age. They were divided into four groups: ENNG + ChL
      (control), ENNG + TAM, ENNG + E(2) and ENNG + TAM + E(2). Endometrial
      proliferative lesions (hyperplasias and/or carcinomas) were observed in all
      groups, the incidences in the TAM- and/or E(2)-treated groups being two times
      higher than in the ChL-treated control animals. High induction (11/20, 55%) of
      adenocarcinomas was observed in the E(2) group but this was significantly
      decreased in combination with TAM (2/20, 10%), no carcinomas being found in the
      TAM group. In experiment II, animals pre-treated with TAM (10 weeks) and
      receiving E(2) post-treated (4 weeks) developed adenocarcinomas, although no
      cancers were observed in mice treated by ChL instead of TAM. In animals pre
      treated with TAM and post-treated with ChL or TAM, no adenocarcinomas were also
      developed. In OVX mice (experiment III), proliferative lesions were observed in
      the TAM- and/or E(2)-treated groups, at incidences significantly higher than in
      ChL-treated animals, in which these lesions were completely absent. However, no
      adenocarcinomas were found, only slight hyperplasias being observed in the TAM
      group, although the incidence of adenocarcinoma was highest in the E(2) alone
      group, and significantly decreased in combination with TAM, as in experiment I.
      These results indicate that TAM may itself exert promotion effects, while
      exhibiting an anti-progression influence on uterine carcinogenesis in adult mice
      initiated by ENNG and receiving E(2).

PMID- 12189201
TI  - Evidence for a role for protein tyrosine phosphatase in the control of ion
      release from the guard cell vacuole in stomatal closure.
AB  - Protein tyrosine phosphatases (PTPases) exist in plants, but their role in plant
      signaling processes is unknown. One of the most important signaling networks in
      plants concerns the regulation of stomatal aperture, by which closure of stomatal
      pores restricts water loss in dry conditions, a process essential for plant
      survival. Closure is achieved by reduction in guard cell volume as a consequence
      of net efflux of potassium salt at both plasmalemma and tonoplast. To test
      whether protein tyrosine phosphorylation has any role in guard cell signaling
      processes, the effects on stomatal aperture and on guard cell K(Rb) fluxes of a
      number of specific inhibitors of PTPases have been investigated. Stomatal closure
      induced by abscisic acid, high external Ca(2+), hydrogen peroxide, and dark were
      all prevented by one such inhibitor, phenylarsine oxide, which added to closed
      stomata promoted reopening. Flux measurements with (86)Rb(+) identified the
      efflux across the tonoplast as the sensitive process, implying that protein
      tyrosine dephosphorylation must occur at or downstream of the Ca(2+) signal
      responsible for triggering ion efflux from the vacuole. There was no inhibition
      of efflux at the plasmalemma. A second inhibitor of PTPases, 3,4 dephosphatin,
      gave very similar effects, inhibiting closure induced by abscisic acid, high
      external Ca(2+), and dark, and promoting reopening if added to closed stomata.
      Again, the efflux of K(Rb) at the tonoplast was the sensitive process. These
      results provide clear evidence for the involvement of PTPases in a major
      signaling network in plants.

PMID- 12189202
TI  - The C2A domain of JFC1 binds to 3'-phosphorylated phosphoinositides and directs
      plasma membrane association in living cells.
AB  - Phosphatidylinositol 3-kinase products play a central role in the regulation of
      several intracellular pathways via adaptor proteins that share the ability to
      bind to 3'-phosphoinositides with high affinity and specificity. JFC1 is a C2
      domain-containing protein involved in cellular trafficking that has been shown to
      bind 3'-phosphoinositides in vitro. In this work, we demonstrate that the C2A
      domain of JFC1 is the module responsible for its binding to the plasma membrane
      via 3'-phosphoinositides in vivo. We show that the C2A domain of JFC1 is the only
      domain present in this protein that localizes to the plasma membrane in living
      cells. Moreover, the C2A domain of JFC1 binds 3'-phosphoinositides in vitro with
      similar specificity as that described for full-length JFC1, suggesting that the
      domain mediates the specific membrane localization of the full-length protein.
      Furthermore, the C2A domain of JFC1 colocalized with the pleckstrin homology
      domain of Akt in vivo, and both the JFC1 C2A domain and the full-length JFC1
      dissociated from the membrane in the presence of PI 3-kinase specific inhibitors.
      We also show that the association of the C2A domain to the membrane is modulated
      by calcium. From these results we analyze possible mechanisms for the role of
      JFC1 in cellular trafficking.

PMID- 12189203
TI  - Synergistic interaction between adenosine A2A and glutamate mGlu5 receptors:
      implications for striatal neuronal function.
AB  - The physiological meaning of the coexpression of adenosine A2A receptors and
      group I metabotropic glutamate receptors in gamma- aminobutyric acid (GABA)ergic
      striatal neurons is intriguing. Here we provide in vitro and in vivo evidence for
      a synergism between adenosine and glutamate based on subtype 5 metabotropic
      glutamate (mGluR5) and adenosine A2A (A2AR) receptor/receptor interactions.
      Colocalization of A2AR and mGluR5 at the membrane level was demonstrated in
      nonpermeabilized human embryonic kidney (HEK)-293 cells transiently cotransfected
      with both receptors by confocal laser microscopy. Complexes containing A2AR and
      mGluR5 were demonstrated by Western blotting of immunoprecipitates of either Flag
      A2AR or hemagglutinin-mGluR5 in membrane preparations from cotransfected HEK-293
      cells and of native A2AR and mGluR5 in rat striatal membrane preparations. In
      cotransfected HEK-293 cells a synergistic effect on extracellular signal
      regulated kinase 1/2 phosphorylation and c-fos expression was demonstrated upon
      A2AR/mGluR5 costimulation. No synergistic effect was observed at the second
      messenger level (cAMP accumulation and intracellular calcium mobilization).
      Accordingly, a synergistic effect on c-fos expression in striatal sections and on
      counteracting phencyclidine-induced motor activation was also demonstrated after
      the central coadministration of A2AR and mGluR5 agonists to rats with intact
      dopaminergic innervation. The results suggest that a functional mGluR5/A2AR
      interaction is required to overcome the well-known strong tonic inhibitory effect
      of dopamine on striatal adenosine A2AR function.

PMID- 12189204
TI  - Specificity of RNA-RNA helix recognition.
AB  - Functional RNAs often form compact structures characterized by closely packed
      helices. Crystallographic analysis of several large RNAs revealed a prevalent
      interaction in which unpaired adenosine residues dock into the minor groove of a
      receptor helix. This A-minor motif, potentially the most important element
      responsible for global RNA architecture, has also been suggested to contribute to
      the fidelity of protein synthesis by discriminating against near-cognate tRNAs on
      the ribosome. The specificity of A-minor interactions is fundamental to RNA
      tertiary structure formation, as well as to their proposed role in translational
      accuracy. To investigate A-minor motif specificity, we analyzed mutations in an A
      minor interaction within the Tetrahymena group I self-splicing intron.
      Thermodynamic and x-ray crystallographic results show that the A-minor
      interaction strongly prefers canonical base pairs over base mismatches in the
      receptor helix, enabling RNA interhelical packing through specific recognition of
      Watson-Crick minor groove geometry.

PMID- 12189205
TI  - The histone deacetylase inhibitor SAHA arrests cancer cell growth, up-regulates
      thioredoxin-binding protein-2, and down-regulates thioredoxin.
AB  - Suberoylanilide hydroxamic acid (SAHA) is a potent inhibitor of histone
      deacetylases (HDACs) that causes growth arrest, differentiation, and/or apoptosis
      of many tumor types in vitro and in vivo. SAHA is in clinical trials for the
      treatment of cancer. HDAC inhibitors induce the expression of less than 2% of
      genes in cultured cells. In this study we show that SAHA induces the expression
      of vitamin D-up-regulated protein 1/thioredoxin-binding protein-2 (TBP-2) in
      transformed cells. As the expression of TBP-2 mRNA is increased, the expression
      of a second gene, thioredoxin, is decreased. In transient transfection assays,
      HDAC inhibitors induce TBP-2 promoter constructs, and this induction requires an
      NF-Y binding site. We report here that TBP-2 expression is reduced in human
      primary breast and colon tumors compared with adjacent tissue. These results
      support a model in which the expression of a subset of genes (i.e., including TBP
      2) is repressed in transformed cells, leading to a block in differentiation, and
      culture of transformed cells with SAHA causes re-expression of these genes,
      leading to induction of growth arrest, differentiation, and/or apoptosis.

PMID- 12189206
TI  - Specification of unique Pit-1 activity in the hGH locus control region.
AB  - The human GH (hGH) gene cluster is regulated by a remote 5' locus control region
      (LCR). HSI, an LCR component located 14.5 kb 5' to the hGH-N promoter,
      constitutes the primary determinant of high-level hGH-N activation in pituitary
      somatotropes. HSI encompasses an array of three binding sites for the pituitary
      specific POU homeodomain factor Pit-1. In the present report we demonstrate that
      all three Pit-1 sites in the HSI array contribute to LCR activity in vivo.
      Furthermore, these three sites as a unit are fully sufficient for position
      independent and somatotrope-restricted hGH-N transgene activation. In contrast,
      the hGH-N transgene is not activated by Pit-1 sites native to either the hGH-N or
      rat (r)GH gene promoters. These findings suggest that the structures of the Pit-1
      binding sites at HSI specify distinct chromatin-dependent activities essential
      for LCR-mediated activation of hGH in the developing pituitary.

PMID- 12189207
TI  - Dysregulated T helper cell differentiation in the absence of interferon
      regulatory factor 4.
AB  - Certain IFN regulatory factor (IRF) transcription factors indirectly influence T
      helper (Th) cell differentiation by regulating the production of IL-12. Here, we
      show that IRF4 directly regulates Th cell differentiation in vitro and in vivo
      during murine leishmaniasis. In the absence of IRF4, IL-12-induced Th1 cell
      differentiation was compromised, while IL-4 failed to induce Th2 cell
      differentiation. Instead, IL-4 tended to induce Th1 cells, defined by production
      of IFN-gamma and TNF. Although early IL-4 signaling was normal in IRF4(-/-) Th
      cells, the protein GATA-3, a transcription factor critical for Th2 development,
      was not up-regulated following IL-4 treatment. Retroviral overexpression of GATA
      3 rescued Th2 differentiation. Therefore, IRF4 deficiency manifests itself as
      severely dysregulated Th cell differentiation.

PMID- 12189208
TI  - Identification of a transcriptionally active peroxisome proliferator-activated
      receptor alpha -interacting cofactor complex in rat liver and characterization of
      PRIC285 as a coactivator.
AB  - Peroxisome proliferator-activated receptor alpha (PPAR alpha) plays a central
      role in the cell-specific pleiotropic responses induced by structurally diverse
      synthetic chemicals designated as peroxisome proliferators. Transcriptional
      regulation by liganded nuclear receptors involves the participation of cofactors
      that form multiprotein complexes to achieve cell- and gene-specific
      transcription. Here we report the identification of such a transcriptionally
      active PPAR alpha-interacting cofactor (PRIC) complex from rat liver nuclear
      extracts that interacts with full-length PPAR alpha in the presence of
      ciprofibrate, a synthetic ligand, and leukotriene B(4), a natural ligand. The
      liganded PPAR alpha-PRIC complex enhanced transcription from a peroxisomal enoyl
      CoA hydratase/l-3-hydroxyacyl-CoA dehydrogenase bifunctional enzyme gene promoter
      template that contains peroxisome proliferator response elements. Rat liver PRIC
      complex comprises some 25 polypeptides, and their identities were established by
      mass spectrometry and limited sequence analysis. Eighteen of these peptides
      contain one or more LXXLL motifs necessary for interacting with nuclear
      receptors. PRIC complex includes known coactivators or coactivator-binding
      proteins (CBP, SRC-1, PBP, PRIP, PIMT, TRAP100, SUR-2, and PGC-1), other proteins
      that have not previously been described in association with transcription
      complexes (CHD5, TOG, and MORF), and a few novel polypeptides designated PRIC300,
      -285, -215, -177, and -145. We describe the cDNA for PRIC285, which contains five
      LXXLL motifs. It interacts with PPAR alpha and acts as a coactivator by
      moderately stimulating PPAR alpha-mediated transcription in transfected cells. We
      conclude that liganded PPAR alpha recruits a distinctive multiprotein complex
      from rat liver nuclear extracts. The composition of this complex may provide
      insight into the basis of tissue and species sensitivity to peroxisome
      proliferators.

PMID- 12189209
TI  - Molecular chaperones as modulators of polyglutamine protein aggregation and
      toxicity.
AB  - The formation of insoluble protein aggregates in neurons is a hallmark of
      neurodegenerative diseases caused by proteins with expanded polyglutamine (polyQ)
      repeats. However, the mechanistic relationship between polyQ aggregation and its
      toxic effects on neurons remains unclear. Two main hypotheses have been put
      forward for how polyQ expansions may cause cellular dysfunction. In one model
      neurotoxicity results from the ability of polyQ-expanded proteins to recruit
      other important cellular proteins with polyQ stretches into the aggregates. In
      the other model, aggregating polyQ proteins partially inhibit the ubiquitin
      proteasome system for protein degradation. These two mechanisms are not exclusive
      but may act in combination. In general, protein misfolding and aggregation are
      prevented by the machinery of molecular chaperones. Some chaperones such as the
      members of the Hsp70 family also modulate polyQ aggregation and suppress its
      toxicity. These recent findings suggest that an imbalance between the neuronal
      chaperone capacity and the production of potentially dangerous polyQ proteins may
      trigger the onset of polyQ disease.

PMID- 12189210
TI  - Induction and maintenance of nonsymmetrical DNA methylation in Neurospora.
AB  - One can imagine a variety of mechanisms that should result in self-perpetuating
      biological states. It is generally assumed that cytosine methylation is
      propagated in eukaryotes by enzymes that specifically methylate hemimethylated
      symmetrical sites (e.g., (5')CpGGpC(5') or (5')CpNpGGpNpC(5')). Although there is
      wide support for this model, we and others have found examples of methylation
      that must be propagated by a different mechanism. Most methylated regions of the
      Neurospora genome that have been examined are products of repeat-induced point
      mutation, a premeiotic genome defense system that litters duplicated sequences
      with C.G to T.A mutations and typically leaves them methylated at remaining
      cytosines. In general, such relics of repeat-induced point mutation are capable
      of triggering methylation de novo. Nevertheless, some reflect a mechanism that
      can propagate heterogeneous methylation at nonsymmetrical sites. We propose that
      de novo and maintenance methylation are manifestations of a single mechanism in
      Neurospora, catalyzed by the DIM-2 DNA methyltransferase. The action of DIM-2 is
      controlled by the DIM-5 histone H3 Lys-9 methyltransferase, which in turn is
      influenced by other modifications of histone H3. DNA methylation indirectly
      recruits histone deacetylases, providing the framework of a self-reinforcing
      system that could result in propagation of DNA methylation and the associated
      silenced chromatin state.

PMID- 12189212
TI  - Optimizing grain yields reduces CH4 emissions from rice paddy fields.
AB  - Microbial production in anoxic wetland rice soils is a major source of
      atmospheric CH4 the most important non-CO2 greenhouse gas. Much higher CH4
      emissions from well managed irrigated rice fields in the wet than in the dry
      season could not be explained by seasonal differences in temperature. We
      hypothesized that high CH4 emissions in the wet season are caused by low grain to
      biomass ratios. In a screenhouse experiment, removing spikelets to reduce the
      plants' capacity to store photosynthetically fixed C in grains increased CH4
      emissions, presumably via extra C inputs to the soil. Unfavorable conditions for
      spikelet formation in the wet season may similarly explain high methane
      emissions. The observed relationship between reduced grain filling and CH4
      emission provides opportunities to mitigate CH4 emissions by optimizing rice
      productivity.

PMID- 12189211
TI  - The Alzheimer's A beta -peptide is deposited at sites of complement activation in
      pathologic deposits associated with aging and age-related macular degeneration.
AB  - Age-related macular degeneration (AMD) is a leading cause of irreversible vision
      loss in older individuals worldwide. The disease is characterized by abnormal
      extracellular deposits, known as drusen, that accumulate along the basal surface
      of the retinal pigmented epithelium. Although drusen deposition is common in
      older individuals, large numbers of drusen and/or extensive areas of confluent
      drusen represent a significant risk factor for AMD. Widespread drusen deposition
      is associated with retinal pigmented epithelial cell dysfunction and degeneration
      of the photoreceptor cells of the neural retina. Recent studies have shown that
      drusen contain a variety of immunomodulatory molecules, suggesting that the
      process of drusen formation involves local inflammatory events, including
      activation of the complement cascade. Similar observations in Alzheimer's disease
      (AD) have lead to the hypothesis that chronic localized inflammation is an
      important element of AD pathogenesis, with significant neurodegenerative
      consequences. Accordingly, the amyloid beta (A beta) peptide, a major constituent
      of neuritic plaques in AD, has been implicated as a primary activator of
      complement in AD. Here we show that A beta is associated with a substructural
      vesicular component within drusen. A beta colocalizes with activated complement
      components in these "amyloid vesicles," thereby identifying them as potential
      primary sites of complement activation. Thus, A beta deposition could be an
      important component of the local inflammatory events that contribute to atrophy
      of the retinal pigmented epithelium, drusen biogenesis, and the pathogenesis of
      AMD.

PMID- 12189213
TI  - Reactions of cysteines substituted in the amphipathic N-terminal tail of a
      bacterial potassium channel with hydrophilic and hydrophobic maleimides.
AB  - Single cysteine-substitution mutants of KcsA, a K(+) channel from Streptomyces
      lividans, were expressed in Escherichia coli, and inner membranes were isolated.
      The rate constants for the reactions of these cysteines with three maleimides of
      increasing hydrophobicity, 4-(N-maleimido)phenyltrimethylammonium, N
      phenylmaleimide, and N-(1-pyrenyl)maleimide, were determined by back titration of
      the remaining cysteines with methoxypolyethylene glycol-2-pyridine disulfide
      (M(r) 3,000) and quantitation of the fraction of gel-shifted KcsA as a function
      of reaction time. The patterns of the rate constants for the reactions of all
      three reagents with eight consecutive cysteines in the partially lipid-immersed
      amphipathic N-terminal tail helix were the same, with cysteines on the
      hydrophilic side of the helix reacting faster than Cys on the hydrophobic side.
      The results are consistent with the tail helix lying with its long axis in the
      lipid-water interface and with the orientation of the helix fluctuating around
      this axis. The patterns of the rate constants for the three reagents were similar
      to the pattern of the probabilities that the substituted cysteines were exposed
      to water, based on the sum of the free energies of transfer from water to octanol
      of all of the residues exposed to lipid in each orientation of the helix.

PMID- 12189214
TI  - The need for and characteristics of randomized, phase III trials to evaluate
      symptom management in patients with cancer.

PMID- 12189215
TI  - Genetic risk in context: calculating the penetrance of BRCA1 and BRCA2 mutations.

PMID- 12189216
TI  - St. John's Wort: more implications for cancer patients.

PMID- 12189217
TI  - Program aims to reduce cancer burden in Appalachia.

PMID- 12189218
TI  - Lung cancer death rates in Appalachia, 1994-1998.

PMID- 12189219
TI  - FDA evaluating oxaliplatin for advanced colorectal cancer treatment.

PMID- 12189220
TI  - Initiative to focus on boosting enrollment in clinical trials.

PMID- 12189221
TI  - Heat shock protein inhibitor shows antitumor activity.

PMID- 12189222
TI  - Clinical utility of proton magnetic resonance spectroscopy in characterizing
      breast lesions.
AB  - Proton magnetic resonance spectroscopy ((1)H MRS) of the breast has been proposed
      as an adjunct to the magnetic resonance imaging (MRI) examination to improve the
      specificity of distinguishing malignant breast tumors from benign breast tumors.
      In this review, we carry out a pooled analysis of the clinical breast (1)H MRS
      studies undertaken to date to determine the factors that influence the diagnostic
      performance of this method. In total, five studies of breast (1)H MRS from four
      independent centers around the world have been published to date. Altogether, 153
      tumors were examined, 100 of which were confirmed histologically to be malignant
      and 53 of which were benign. The lesions presenting a detectable composite
      choline signal in their corresponding (1)H MR spectra were diagnosed as
      malignant, whereas the lesions with no choline signal were diagnosed as benign.
      The sensitivity and specificity of breast (1)H MRS for detecting breast cancer
      were 83% (95% confidence interval [CI] = 73% to 89%) and 85% (95% CI = 71% to
      93%), respectively, and both values could be as high as 92% after technical
      exclusions. In a subgroup of 20 young women, the sensitivity and the specificity
      of the method approached 100%. The factors limiting the sensitivity of the
      examination were mainly technical. The use of the composite choline signal as a
      marker for malignancy in breast (1)H MRS is a robust method with highly reliable
      interpretation, because it is based on the appearance of a single peak. The
      method is likely to provide even better results with technologic advances in
      breast MRS that lead to the improved detection of the composite choline signal.

PMID- 12189223
TI  - Trends in Kaposi's sarcoma and non-Hodgkin's lymphoma incidence in the United
      States from 1973 through 1998.
AB  - BACKGROUND: The incidence of Kaposi's sarcoma (KS) and non-Hodgkin's lymphoma
      (NHL) in the general population has markedly increased since the onset of the
      AIDS epidemic in 1981. However, during the 1990s, the dynamics of the AIDS
      epidemic changed, as human immunodeficiency virus (HIV) infection rates slowed
      and effective antiretroviral therapies were introduced. We examined the impact of
      these changes on the general population incidence of KS and NHL. METHODS: Age
      standardized incidences for KS and NHL from 1973 through 1998 were obtained from
      nine population-based cancer registries that participate in the Surveillance,
      Epidemiology and End Results (SEER) program. RESULTS: During the mid-1990s, KS
      incidence declined sharply in all nine registries. Decreases in KS incidence were
      most evident in San Francisco, where KS rates among white men had risen from 0.5
      per 100 000 people per year in 1973 to between 31.1 and 33.3 from 1987 through
      1991 and then declined to 2.8 in 1998. With background NHL incidence in the
      general population being much higher than that for KS, changes in incidence
      related to the AIDS epidemic were most evident in subgroups at high risk of AIDS.
      In San Francisco, NHL rates among white men rose from 10.7 in 1973 to a peak of
      31.4 in 1995 and then declined to 21.6 in 1998. NHL types that were most highly
      AIDS-associated declined most steeply, whereas the incidence of NHL types not
      associated with AIDS was either stable or increasing. CONCLUSION: Changes in KS
      and NHL incidence since the mid 1990s may reflect declines in the number of
      individuals with AIDS and improved immune function in such individuals following
      the introduction of effective antiretroviral therapies in the 1990s. Notably, non
      AIDS-associated NHL incidence has continued to increase steadily through 1998.

PMID- 12189225
TI  - On the use of familial aggregation in population-based case probands for
      calculating penetrance.
AB  - BACKGROUND: Estimating the lifetime risk associated with (i.e., the penetrance
      of) genetic abnormalities that predispose individuals to cancer is important for
      genetic counseling. (Penetrance may be estimated from the degree of familial
      aggregation of cancer, that is, the extent to which cancers cluster in families.)
      Early penetrance studies of BRCA1 and BRCA2 mutations used high-risk families
      with multiple cases of breast cancer, a study design that led to very high
      penetrance estimates. However, such studies were subject to potential
      ascertainment biases. To offset such biases, recent studies have used data from
      family members of probands ascertained from population-based incident cases of
      cancer. The use of case probands is, however, also subject to bias because all
      risk factors are over-represented in case patients. To draw attention to this
      problem, literature on the penetrance of breast cancer in BRCA1 and BRCA2
      carriers is reviewed. METHODS: A theory is presented to show that the use of case
      probands is itself biased, leading to inflated penetrance estimates. The strategy
      is unbiased only if all carriers share an identical risk. Any unexplained
      heterogeneity of risk caused by unknown genetic or shared environmental factors
      within families leads to an inflated estimate of penetrance. RESULTS: Eight
      published studies using population-based methods are reviewed. All but one of the
      family-based studies used case probands. CONCLUSIONS: Penetrance estimates from
      case proband studies must be inflated if other factors influence breast cancer
      risk in addition to the specific genetic abnormality. Thus, women with such
      genetic abnormalities and a strong family history of breast cancer are likely to
      possess a much higher risk for breast cancer than women with such abnormalities
      but without a strong family history. Methodologic techniques to improve the
      prediction of cancer risk are needed.

PMID- 12189224
TI  - Double-blind, placebo-controlled, randomized phase III trial of darbepoetin alfa
      in lung cancer patients receiving chemotherapy.
AB  - BACKGROUND: Patients receiving chemotherapy often develop anemia. Darbepoetin
      alfa (Aranesp(TM)) is an erythropoiesis-stimulating glycoprotein that has been
      shown, in dose-finding studies, to be safe and clinically active when
      administered to patients with cancer every 1, 2, or 3 weeks. This phase III study
      compared the safety and efficacy of darbepoetin alfa with placebo in patients
      with lung cancer receiving chemotherapy. METHODS: In this multicenter, double
      blind, placebo-controlled study, 320 anemic patients (hemoglobin <or=11.0 g/dL)
      were randomly assigned to receive darbepoetin alfa or placebo injections weekly
      for 12 weeks. The 297 patients who completed at least the first 28 days of study
      were assessed for red blood cell transfusions, the primary endpoint. Patients
      were also assessed for hemoglobin concentration (i.e., hematopoietic response),
      adverse events, antibody formation to darbepoetin alfa, hospitalizations,
      Functional Assessment of Cancer Therapy (FACT)-Fatigue score, and disease
      outcome. Efficacy endpoints were assessed using Kaplan-Meier analyses, Cox
      proportional hazards analyses, and chi-square tests where appropriate. All
      statistical tests were two-sided. RESULTS: Patients receiving darbepoetin alfa
      required fewer transfusions (27% versus 52%; mean difference = 25%; 95%
      confidence interval [CI] = 14% to 36%; P<.001), required fewer units of blood
      (0.67 versus 1.92; mean difference = 1.25, 95% CI = 0.65 to 1.84; P<.001), had
      more hematopoietic responses (66% versus 24%; mean difference = 42%; 95% CI = 31%
      to 53%; P<.001), and had better improvement in FACT-Fatigue scores (56% versus
      44% overall improvement; 32% versus 19% with >or=25% improvement; mean difference
      = 13%; 95% CI = 2% to 23%, P =.019) than patients receiving placebo. Patients
      receiving darbepoetin alfa did not appear to have any untoward effect in disease
      outcome and did not develop antibodies to the drug. Adverse events were similar
      between the groups. CONCLUSIONS: Patients with chemotherapy-associated anemia can
      safely and effectively be treated with weekly darbepoetin alfa therapy.
      Darbepoetin alfa decreased blood transfusion requirements, increased hemoglobin
      concentration, and decreased fatigue. Although no conclusions can be drawn about
      survival from this study, the potential salutary effect on disease outcome
      warrants further investigation in a prospectively designed study.

PMID- 12189226
TI  - The effects of adrenomedullin overexpression in breast tumor cells.
AB  - BACKGROUND: Adrenomedullin is a secreted peptide hormone with multiple
      activities. Several reports have indicated that adrenomedullin may be involved in
      tumor survival, but this has not been directly shown. Here we evaluate the in
      vitro and in vivo effects of adrenomedullin overexpression in human breast cancer
      cells. METHODS: The human breast cancer cell lines T47D and MCF7, both of which
      express low basal levels of adrenomedullin, were stably transfected with an
      expression construct that contained the coding region of the human adrenomedullin
      gene or with empty expression vector. Properties of the transfected cells were
      assessed by proliferation and apoptosis assays, in vitro and in vivo angiogenesis
      assays, cell migration experiments, and xenograft implants. The effect of
      synthetic adrenomedullin on human ovarian (ECV) cancer cell motility was also
      tested. Western blot analysis was used to compare expression levels of several
      genes whose products are associated with cell growth and regulation of apoptosis.
      RESULTS: T47D and MCF7 cells transfected with the adrenomedullin construct both
      expressed high levels of adrenomedullin mRNA and protein. Compared with cells
      transfected with empty vector, cells that overexpressed adrenomedullin displayed
      a more pleiotropic morphology, an increased angiogenic potential both in vitro
      and in vivo, and less apoptosis after serum deprivation. T47D and MCF7 cells did
      not display measurable motility, but ECV ovarian cancer cells treated with
      synthetic adrenomedullin were more motile than saline-treated ECV cells.
      Adrenomedullin-overexpressing T47D cells had higher levels of proteins involved
      in oncogenic signal transduction pathways (such as Ras, Raf, PKC, and MAPKp49)
      and lower levels of pro-apoptotic proteins (such as Bax, Bid, and caspase 8) than
      T47D cells transfected with empty vector. In a preliminary in vivo experiment,
      three of 10 nude mice injected with adrenomedullin-overexpressing T47D cells
      developed xenograft tumors, whereas none of the 10 nude mice injected with cells
      carrying the empty plasmid developed tumors. CONCLUSIONS: These results further
      support the role of adrenomedullin as a survival factor for tumors. Development
      of physiologically efficient inhibitors of adrenomedullin may prove useful in the
      clinical management of cancer.

PMID- 12189227
TI  - Risk factors for breast cancer at young ages in twins: an international
      population-based study.
AB  - BACKGROUND: Breast cancer etiology in women may relate to exposures early in life
      as well as in adulthood, but it has been difficult to gain information on
      childhood variables, and evidence on their effects is very limited. Comparison of
      risk factor levels between affected probands and unaffected twins in twin pairs
      can provide a unique method to investigate risk factors that act in early life.
      METHODS: We conducted four population-based case-control studies of breast cancer
      risk in twins in Denmark, England and Wales, Finland, and Sweden and pooled the
      data from these studies. The case patients were 400 women with incident breast
      cancer before the age of 50 years, and the control subjects were their twin
      sisters who had not had breast cancer by that time. Data on risk factors (e.g.,
      demographic and anthropomorphic variables, reproductive history, and family
      history) were collected by interview and by a mailed questionnaire and were
      analyzed by calculating matched odds ratios [ORs]. All statistical tests were two
      sided. RESULTS: The risk of breast cancer was increased for women who were less
      obese (OR = 1.44, 95% confidence interval [CI] = 1.08 to 1.91) or taller (OR =
      1.27, 95% CI = 0.95 to 1.70) than their co-twin at age 10 years, for women who
      developed breasts earlier than their co-twin (OR = 1.53, 95% CI = 1.14 to 2.06),
      and for women who had a smaller waist-to-hip ratio at age 20 years than their co
      twin (OR = 1.79, 95% CI = 1.00 to 3.21). Analysis according to family history of
      breast cancer showed that the associations of childhood height and weight with
      risk of breast cancer were only apparent in women without a family history of
      breast cancer. CONCLUSIONS: Childhood growth before puberty may affect the risk
      of premenopausal breast cancer, at least in women without a family history of
      breast cancer. The distribution of body fat in young adulthood may also be
      related to breast cancer risk.

PMID- 12189228
TI  - Effects of St. John's wort on irinotecan metabolism.
AB  - St. John's wort (SJW), a widely used herbal product, has been implicated in drug
      interactions resulting from the induced expression of the cytochrome P450 CYP3A4
      isoform. In this study, we determined the effect of SJW on the metabolism of
      irinotecan, a pro-drug of SN-38 and a known substrate for CYP3A4. Five cancer
      patients were treated with irinotecan (350 mg/m(2), intravenously) in the
      presence and absence of SJW (900 mg daily, orally for 18 days) in an unblinded,
      randomized crossover study design. The plasma levels of the active metabolite SN
      38 decreased by 42% (95% confidence interval [CI] = 14% to 70%) following SJW
      cotreatment with 1.0 micro M x h (95% CI = 0.34 micro M x h to 1.7 micro M x h)
      versus 1.7 micro M x h (95% CI = 0.83 micro M x h to 2.6 micro M x h) (P =.033,
      two-sided paired Student's t test). Consequently, the degree of myelosuppression
      was substantially worse in the absence of SJW. These findings indicate that
      patients on irinotecan treatment should refrain from taking SJW because plasma
      levels of SN-38 were dramatically reduced, which may have a deleterious impact on
      treatment outcome.

PMID- 12189230
TI  - Re: Race, socioeconomic status, and breast cancer treatment and survival.

PMID- 12189229
TI  - Association of human papillomavirus type 58 variant with the risk of cervical
      cancer.
AB  - Human papillomavirus (HPV) type 58 has been found to be prevalent among Chinese
      patients with cervical cancer. This study examined the oncogenic risk of HPV58
      variants in Hong Kong, a southern part of China. Altogether, 1924 women were
      studied: 42.8% with a normal cervix, 16.2% with cervical intraepithelial
      neoplasia (CIN) I, 12.7% with CIN II, 20.8% with CIN III, and 7.6% with invasive
      cervical cancer (ICC). The overall prevalence of HPV58 was 11.4% (220) and
      increased statistically significantly with the severity of neoplasia
      (P(trend)<.001, chi(2) test for trend). Among HPV58-positive women, the
      occurrence of E7 632C-->T (T20I) and E7 760G-->A (G63S) variants (T20I/G63S)
      showed a positive trend of association with the severity of neoplasia
      (P(trend)<.001, chi(2) test for trend). HPV58 variants carrying these two
      substitutions showed an odds ratio (OR) for ICC of 26.79 (95% confidence interval
      = 10.14 to 74.72), and this OR was 6.9-fold higher than the ORs of variants
      without these substitutions. Patients with CIN III or ICC who were also infected
      with T20I/G63S variants had a statistically significant younger age at diagnosis
      than those infected with other variants (median age = 37 years versus 48 years; P
      =.038, two-sided Mann-Whitney U test). Thus, HPV58 variants carrying E7 T20I/G63S
      substitutions may be associated with an increased risk for cervical cancer.

PMID- 12189232
TI  - Re: Reproductive hormone-induced, STAT3-mediated interleukin 6 action in normal
      and malignant human ovarian surface epithelial cells.

PMID- 12189233
TI  - When science rides the MTA.

PMID- 12189234
TI  - The lung as a metabolic factory for gene therapy.

PMID- 12189235
TI  - Clinical use of TNF revisited: improving penetration of anti-cancer agents by
      increasing vascular permeability.

PMID- 12189237
TI  - Home sweet home: How do virus specific T cells navigate to the skin?

PMID- 12189236
TI  - Malnutrition: a frequent misdiagnosis for hemodialysis patients.

PMID- 12189238
TI  - UV-induction of keratinocyte endothelin-1 downregulates E-cadherin in melanocytes
      and melanoma cells.
AB  - Endothelin-1 (ET-1), a peptide that is secreted by keratinocytes in the skin in
      response to ultraviolet irradiation, is a ligand for the endothelin-B (ET(B))
      receptor. Blockade of this receptor inhibits melanoma cell growth and induces
      cell death in vivo and in vitro. Additionally, ET(B) is a melanoma progression
      marker. These findings suggest that the ET-1/ET(B) receptor pathway contributes
      to melanoma development or progression. Here, we demonstrate that activation of
      the ET-1/ET(B) pathway downregulates E-cadherin and associated catenin proteins
      in human melanocytes and melanoma cells. E-cadherin is an established suppressor
      of melanoma cell invasion in vitro and in vivo. Downregulation of E-cadherin by
      ET-1/ET(B) involves the downstream activation of caspase-8 but not of distal,
      executioner caspases, and does not lead to apoptosis. ET-1 also induces a
      transient association between caspase-8 and E-cadherin:beta-catenin complexes.
      Hence, activation of the ET-1/ET(B) pathway promotes molecular events known to
      promote melanoma invasion.

PMID- 12189239
TI  - Characterization of novel breast carcinoma-associated BA46-derived peptides in
      HLA-A2.1/D(b)-beta2m transgenic mice.
AB  - The human milk fat globule membrane protein BA46 (lactadherin) is highly
      overexpressed in human breast tumors, making it a potential target for tumor
      immunotherapy. We have identified BA46-derived peptides that contain the motif
      recognized by the MHC class I molecule HLA-A2.1 and that are processed and
      presented by human breast carcinoma cells. In mice lacking normal class I
      molecules but expressing an HLA-A2.1/D(b)-beta2 microglobulin single chain (HHD
      mice), three peptides elicited specific CTL activity. Two of these peptides also
      stimulated cytotoxic activity in peripheral blood lymphocytes from HLA-A2.1
      positive breast carcinoma patients. Adoptive transfer of HHD-derived bulk CTLs to
      nude mice bearing human breast carcinoma transplants reduced tumor growth. These
      peptides therefore represent naturally processed BA46-derived CTL epitopes that
      can be used in peptide-based antitumor vaccines.

PMID- 12189240
TI  - Overlapping and enzyme-specific contributions of matrix metalloproteinases-9 and 
      12 in IL-13-induced inflammation and remodeling.
AB  - IL-13 potently stimulates eosinophilic and lymphocytic inflammation and alveolar
      remodeling in the lung, effects that depend on the induction of various matrix
      metalloproteinases (MMPs). Here, we compared the remodeling and inflammatory
      effects of an IL-13 transgene in lungs of wild-type, MMP-9-deficient, or MMP-12
      deficient mice. IL-13-induced alveolar enlargement, lung enlargement, compliance
      alterations, and respiratory failure and death were markedly decreased in the
      absence of MMP-9 or MMP-12. Moreover, IL-13 potently induced MMPs-2, -12, -13,
      and -14 in the absence of MMP-9, while induction of MMPs-2, -9, -13, and -14 by
      IL-13 was diminished in the absence of MMP-12. A deficiency in MMP-9 did not
      alter eosinophil, macrophage, or lymphocyte recovery, but increased the recovery
      of total leukocytes and neutrophils in bronchoalveolar lavage (BAL) fluids from
      IL-13 transgenic mice. In contrast, a deficiency in MMP-12 decreased the recovery
      of leukocytes, eosinophils, and macrophages, but not lymphocytes or neutrophils.
      These studies demonstrate that IL-13 acts via MMPs-9 and -12 to induce alveolar
      remodeling, respiratory failure, and death and that IL-13 induction of MMPs-2, 
      9, -13, and -14 is mediated at least partially by an MMP-12-dependent pathway.
      The also demonstrate that MMPs-9 and -12 play different roles in the generation
      of IL-13-induced inflammation, with MMP-9 inhibiting neutrophil accumulation and
      MMP-12 contributing to the accumulation of eosinophils and macrophages.

PMID- 12189241
TI  - Improving chemotherapeutic drug penetration in tumors by vascular targeting and
      barrier alteration.
AB  - Drug delivery and penetration into neoplastic cells distant from tumor vessels
      are critical for the effectiveness of solid-tumor chemotherapy. We have found
      that targeted delivery to tumor vessels of picogram doses of TNF-alpha (TNF), a
      cytokine able to alter endothelial barrier function and tumor interstitial
      pressure, enhances the penetration of doxorubicin in tumors in murine models.
      Vascular targeting was achieved by coupling TNF with CNGRC, a peptide that
      targets the tumor neovasculature. This treatment enhanced eight- to tenfold the
      therapeutic efficacy of doxorubicin, with no evidence of increased toxicity.
      Similarly, vascular targeting enhanced the efficacy of melphalan, a different
      chemotherapeutic drug. Synergy with chemotherapy was observed with 3-5 ng/kg of
      targeted TNF (intraperitoneally), about 10(6)-fold lower than the LD(50) and
      10(5)-fold lower than the dose required for nontargeted TNF. In addition, we have
      also found that targeted delivery of low doses of TNF to tumor vessels does not
      induce the release of soluble TNF receptors into the circulation. The delivery of
      minute amounts of TNF to tumor vessels represents a new approach for avoiding
      negative feedback mechanisms and preserving its ability to alter drug-penetration
      barriers. Vascular targeting could be a novel strategy for increasing the
      therapeutic index of chemotherapeutic drugs.

PMID- 12189242
TI  - Intradialytic parenteral nutrition improves protein and energy homeostasis in
      chronic hemodialysis patients.
AB  - Decreased dietary protein intake and hemodialysis-associated protein catabolism
      are among several factors that predispose chronic hemodialysis (CHD) patients to
      protein calorie malnutrition. Since attempts to increase protein intake by
      dietary counseling are usually ineffective, intradialytic parenteral nutrition
      (IDPN) has been proposed as a potential therapeutic approach in malnourished CHD
      patients. In this study, we examined protein and energy homeostasis during
      hemodialysis in seven CHD patients at two separate hemodialysis sessions, with
      and without IDPN administration. Patients were studied 2 hours before, during,
      and 2 hours following a hemodialysis session, using a primed constant infusion of
      L-(1-(13)C) leucine and L-(ring-(2)H(5)) phenylalanine. Our results showed that
      IPDN promoted a large increase in whole-body protein synthesis and a significant
      decrease in whole-body proteolysis, along with a significant increase in forearm
      muscle protein synthesis. The net result was a change from an essentially
      catabolic state to a highly positive protein balance, both in whole-body and
      forearm muscle compartments. We conclude that the provision of calories and amino
      acids during hemodialysis with IDPN acutely reverses the net negative whole-body
      and forearm muscle protein balances, demonstrating a need for long-term clinical
      trials evaluating IDPN in malnourished CHD patients.

PMID- 12189243
TI  - Experimental autoimmune encephalitis and inflammation in the absence of
      interleukin-12.
AB  - IL-12 is considered a critical proinflammatory cytokine for autoimmune diseases
      such as multiple sclerosis and its animal model, experimental autoimmune
      encephalomyelitis (EAE). IL-12 is a heterodimer composed of a p35 subunit and a
      common p40 subunit shared by other cytokines. Both IL-12 p40(-/-) and p35(-/-)
      mice fail to produce IL-12 p70 heterodimer. However, in contrast to p40(-/-)
      mice, p35(-/-) mice are highly susceptible to the induction of EAE, establishing
      that IL-12 p70 is not essential for the development of EAE. When compared with
      wild-type mice, both p40(-/-) and p35(-/-) mice show deficiencies in primary IFN
      gamma responses by lymph node cells. Expression profiling of the inflamed CNS
      revealed that Th2 cytokines such as IL-4 and IL-10 are upregulated in p35(-/-)
      mice, whereas LT-alpha and TNF-alpha levels are reduced. These studies show that
      a molecule other than IL-12 p70, which uses the p40 subunit, fulfills the
      functions previously attributed to IL-12 with regard to the development and
      pathogenesis of this autoimmune disease.

PMID- 12189244
TI  - Noninvasive gene transfer to the lung for systemic delivery of therapeutic
      proteins.
AB  - This study evaluates the use of vectors based on adeno-associated viruses (AAVs)
      to noninvasively deliver genes to airway epithelial cells as a means for
      achieving systemic administration of therapeutic proteins. We intranasally
      delivered AAV vectors to mice in which the same AAV2 genome encoding a cellular
      marker was packaged in capsids from AAV1, 2, or 5 (AAV2/1, AAV2/2, or AAV2/5,
      respectively). Gene expression levels achieved in both airways and alveoli were
      higher with AAV2/5 than with AAV2/1 and were undetectable with AAV2/2. The same
      set of vectors encoding a secreted therapeutic protein, erythropoietin (Epo),
      under the control of a lung-specific promoter (CC10) was intranasally delivered
      to mice, resulting in polycythemia with the highest levels of serum Epo obtained
      with AAV2/5 vectors. After a single intranasal administration of this vector,
      secretion of Epo was documented for 150 days. Similarly, intranasal
      administration of an AAV2/5-CC10-factor IX vector resulted in secretion of
      functional recombinant protein in the bloodstream of hemophiliac, factor IX
      deficient mice. In addition, we demonstrate successful readministration of AAV2/5
      to the lung 5 months after the first delivery of the same vector. In conclusion,
      we show that intranasal administration of AAV vectors results in efficient gene
      transfer to the lung only when the vector contains the AAV5 capsid and that this
      noninvasive route of administration results in sustained secretion of therapeutic
      proteins in the bloodstream.

PMID- 12189245
TI  - Pseudoachondroplasia is caused through both intra- and extracellular pathogenic
      pathways.
AB  - Pseudoachondroplasia is a dominantly inherited chondrodysplasia associated with
      mutations in cartilage oligomeric matrix protein (COMP). Investigations into the
      pathogenesis of pseudoachondroplasia are hampered by its rarity. We developed a
      cell culture model by expressing mutant COMP in bovine primary chondrocytes using
      a gutless adenoviral vector. We show that mutant COMP exerts its deleterious
      effects through both intra- and extracellular pathogenic pathways. Overexpression
      of mutant COMP led to a dose-dependent decrease in cellular viability. The
      secretion of mutant COMP was markedly delayed, presumably due to a prolonged
      association with chaperones in the endoplasmic reticulum (ER). The ECM lacked
      organized collagen fibers and showed amorphous aggregates formed by mutant COMP.
      Thus, pseudoachondroplasia appears to be an ER storage disease, most likely
      caused by improper folding of mutant COMP. The growth failure of affected
      patients may be explained by an increased cell death of growth-plate
      chondrocytes. Dominant interference of the mutant protein on collagen fiber
      assembly could contribute to the observed failure of the ECM of cartilage and
      tendons.

PMID- 12189246
TI  - Identification of ARTS-1 as a novel TNFR1-binding protein that promotes TNFR1
      ectodomain shedding.
AB  - Proteolytic cleavage of TNF receptor 1 (TNFR1) generates soluble receptors that
      regulate TNF bioactivity. We hypothesized that the mechanism of TNFR1 shedding
      might involve interactions with regulatory ectoproteins. Using a yeast two-hybrid
      approach, we identified ARTS-1 (aminopeptidase regulator of TNFR1 shedding) as a
      type II integral membrane protein that binds to the TNFR1 extracellular domain.
      In vivo binding of membrane-associated ARTS-1 to TNFR1 was confirmed by
      coimmunoprecipitation experiments using human pulmonary epithelial and umbilical
      vein endothelial cells. A direct relationship exists between membrane-associated
      ARTS-1 protein levels and concordant changes in TNFR1 shedding. Cells
      overexpressing ARTS-1 demonstrated increased TNFR1 shedding and decreased
      membrane-associated TNFR1, while cells expressing antisense ARTS-1 mRNA
      demonstrated decreased membrane-associated ARTS-1, decreased TNFR1 shedding, and
      increased membrane-associated TNFR1. ARTS-1 neither bound to TNFR2 nor altered
      its shedding, suggesting specificity for TNFR1. Although a recombinant ARTS-1
      protein demonstrated selective aminopeptidase activity toward nonpolar amino
      acids, multiple lines of negative evidence suggest that ARTS-1 does not possess
      TNFR1 sheddase activity. These data indicate that ARTS-1 is a multifunctional
      ectoprotein capable of binding to and promoting TNFR1 shedding. We propose that
      formation of a TNFR1-ARTS-1 molecular complex represents a novel mechanism by
      which TNFR1 shedding is regulated.

PMID- 12189247
TI  - A novel angiogenic pathway mediated by non-neuronal nicotinic acetylcholine
      receptors.
AB  - We have recently reported that nicotine has angiogenic effects, which appear to
      be mediated through non-neuronal nicotinic acetylcholine receptors (nAChRs).
      Here, we describe the endogenous cholinergic pathway for angiogenesis. In an in
      vitro angiogenesis model, increasing concentrations of the nonselective nAChR
      antagonist mecamylamine completely and reversibly inhibited endothelial network
      formation. Although several nAChR isoforms are expressed on endothelial cells
      (ECs), a similar inhibition was only obtained with the selective alpha7-nAChR
      antagonist alpha-bungarotoxin, whereas other selective antagonists did not result
      in significant inhibition of network formation. alpha7-nAChR was upregulated
      during proliferation, by hypoxia in vitro, and by ischemia in vivo. The nAChR
      induced network formation was partially dependent on VEGF, was completely
      dependent on the phosphatidylinositol 3-kinase and mitogen-activated protein
      kinase pathways, and finally resulted in NF-kappaB activation. In vivo,
      pharmacological inhibition of nAChR as well as genetic disruption of alpha7-nAChR
      expression significantly inhibited inflammatory angiogenesis and reduced ischemia
      induced angiogenesis and tumor growth. Our results suggest that nAChRs may play
      an important role in physiological and pathological angiogenesis. To our
      knowledge, this is the first description of a cholinergic angiogenic pathway, and
      it suggests a novel avenue for therapeutic modulation of angiogenesis.

PMID- 12189248
TI  - Expression of cutaneous lymphocyte-associated antigen by CD8(+) T cells specific
      for a skin-tropic virus.
AB  - Virus-specific CD8(+) T cells traffic to infected tissues to promote clearance of
      infection. We used herpes simplex virus type 2 (HSV-2) as a model system to
      investigate CD8(+) T cell trafficking to the skin in humans. Using human
      leukocyte antigen (HLA) class I tetramers, we observed that HSV-specific CD8(+) T
      cells in the peripheral blood expressed high levels of cutaneous lymphocyte
      associated antigen (CLA). In contrast, CD8(+) T cells specific for non-skin
      tropic herpesviruses lacked CLA expression. CLA-positive HSV-2-specific CD8(+) T
      cells had the characteristics of central memory cells, expressing CCR7, CD62L,
      and CD28, and they proliferated briskly in response to antigen. CLA is related to
      a functional E-selectin ligand, and both E-selectin and CLA-positive cells were
      detected in HSV-2-infected skin. HSV-2-specific T cells adhered to cells
      transfected with E-selectin. A higher proportion of HSV-specific CD8(+) T cells
      recovered from herpes lesions express CLA compared with blood, consistent with a
      role for CLA in skin homing. To our knowledge, this is the first report of
      expression of tissue-specific adhesion-associated molecules by virus-specific
      CD8(+) T cells. The evaluation of vaccines for skin and mucosal pathogens should
      include study of the induction of appropriate tissue-specific homing molecules.

PMID- 12189250
TI  - Functional selectin ligands mediating human CD34(+) cell interactions with bone
      marrow endothelium are enhanced postnatally.
AB  - Hematopoietic progenitor cells (HPCs) can home to the bone marrow (BM) after a
      simple intravenous injection, but the adhesive mechanisms mediating the initial
      interactions of human HPCs with the BM endothelium have not been evaluated in
      vivo. Using fluorescence intravital microscopy and homing assays in NOD/SCID
      mice, we show that endothelial selectins are necessary for human adult CD34(+)
      cell homing, since rolling on BM endothelium and retention in the BM compartment
      are drastically reduced (>90%) in endothelial selectin-deficient NOD/SCID mice.
      Comparative analyses of CD34(+) cells collected from adults and from cord blood
      (CB) reveal that neonatal cells display reduced rolling fractions compared with
      adult CD34(+) cells obtained from peripheral blood or BM, suggesting abnormal
      selectin ligand function on neonatal progenitors. Flow cytometric and intravital
      microscopy studies suggest that this defect results from nonfunctional P-selectin
      ligand on a subset ( approximately 30%) of neonatal CD34(+) cells. Further
      analyses indicate that P-selectin glycoprotein ligand-1 (PSGL-1) is expressed in
      a nonfunctional form among neonatal CD34(+) cells that do not bind P-selectin and
      that this subset is enriched in primitive CD34(+)CD38(lo/-) progenitors. These
      results underscore the potential to improve homing of CB CD34(+) cells to the BM
      by manipulation of selectins and their ligands.

PMID- 12189251
TI  - Responding to hypoxia: lessons from a model cell line.
AB  - Mammalian cells require a constant supply of oxygen to maintain adequate energy
      production, which is essential for maintaining normal function and for ensuring
      cell survival. Sustained hypoxia can result in cell death. It is, therefore, not
      surprising that sophisticated mechanisms have evolved that allow cells to adapt
      to hypoxia. "Oxygen-sensing" is a special phenotype that functions to detect
      changes in oxygen tension and to transduce this signal into organ system
      functions that enhance the delivery of oxygen to tissue in various organisms.
      Oxygen-sensing cells can be segregated into two distinct cell types: those that
      functionally depolarize (excitable) and those that do not functionally depolarize
      (nonexcitable) in response to reduced oxygen. Theoretically, excitable cells have
      all the same signaling capabilities as the nonexcitable cells, but the
      nonexcitable cells cannot have all the signaling capabilities as excitable cells.
      A number of signaling pathways have been identified that regulate gene expression
      during hypoxia. These include the Ca2+-calmodulin pathway, the 3'-5' adenosine
      monophosphate (cAMP)-protein kinase A (PKA) pathway, the p42 and p44 mitogen
      activated protein kinase [(MAPK); also known as the extracellular signal-related
      kinase (ERK) for ERK1 and ERK2] pathway, the stress-activated protein kinase
      (SAPK; also known as p38 kinase) pathway, and the phosphatidylinositol 3-kinase
      (PI3K)-Akt pathway. In this review, we describe hypoxia-induced signaling in the
      model O2-sensing rat pheochromocytoma (PC12) cell line, the current level of
      understanding of the major signaling events that are activated by reduced O2, and
      how these signaling events lead to altered gene expression in both excitable and
      nonexcitable oxygen-sensing cells.

PMID- 12189249
TI  - Cyclooxygenase-1-selective inhibition prolongs gestation in mice without adverse
      effects on the ductus arteriosus.
AB  - Preterm delivery is the leading cause of neonatal mortality and contributes
      significantly to infant morbidity. Classical cyclooxygenase (COX) inhibitors,
      such as indomethacin, which inhibit both COX-1 and COX-2, are effective for
      delaying premature labor, but their use is limited by serious complications to
      the fetus and neonate, including adverse effects on the ductus arteriosus (DA).
      Using isoform-selective inhibitors, we characterized the roles of the COX
      isoforms in the initiation of labor and the regulation of fetal and neonatal DA
      closure in mice. Chronic inhibition of COX-2 during pregnancy (gestation days 15
      18) significantly increased neonatal mortality by preventing closure of the DA
      after birth, whereas acute COX-2 inhibition near the end of term (gestation day
      18) constricted the fetal DA. In contrast, the inhibition of COX-1 during
      pregnancy lacked these prenatal and postnatal adverse effects on the DA and
      effectively delayed the initiation of full-term labor and LPS-induced preterm
      labor. These findings suggest that premature fetal DA closure or neonatal patent
      DA observed following indomethacin tocolysis in women may result from the
      inhibition of COX-2. Therefore, COX-1-selective inhibitors may provide effective
      treatment to delay preterm labor with fewer adverse effects on fetal or neonatal
      health than nonselective or COX-2-selective inhibitors.

PMID- 12189252
TI  - Stress response syndromes and cancer: conceptual and assessment issues.
AB  - Stress response syndromes have begun to receive research attention in cancer,
      including melanoma, Hodgkin's disease, breast cancer, and mixed-diagnosis
      samples. This paper focuses on conceptual and assessment issues in the
      application of the trauma model to adaptation to cancer. Among the central
      considerations: differentiating cancer from other traumatic events, the utility
      of conceptualizing stress responses along a continuum in this population,
      diagnostic issues, and preliminary recommendations for therapeutic interventions.

PMID- 12189253
TI  - Childhood antecedents of hypochondriasis.
AB  - According to the interpersonal model of hypochondriasis, early environmental
      adversity may give rise to attachment insecurity that finds adult expression in
      care-seeking behavior. To identify antecedents of this disturbance, we
      interviewed general medicine patients and obtained from them self-reports of
      traumatic events, adverse circumstances, and symptoms experienced in childhood.
      Patients who met DSM-III-R criteria for hypochondriasis more often reported
      traumatic events and circumstances, including serious illness or injury. Among
      all patients, the level of hypochondriacal symptoms in adulthood was correlated
      with poor health, hypochondriacal worry, and separation anxiety in childhood.
      These findings are consistent with a growing literature that links childhood
      adversity to adult hypochondriasis; they support the interpersonal model.

PMID- 12189254
TI  - An open-label clinical trial of nefazodone in hypochondriasis.
AB  - Hypochondriasis is a common and challenging problem in general medical practice,
      but little research is available on pharmacotherapeutic treatment approaches. The
      purpose of the present study was to evaluate the use of nefazodone in the
      treatment of hypochondriasis in an open-label trial. Eleven patients with a
      primary diagnosis of DSM-IV hypochondriasis received an 8-week trial of
      nefazodone with a maximum dose of 600 mg/day and a mean dose of 432 mg. Clinician
      and self-ratings were completed at each of six visits. Nine of the 11 patients
      who started the trial completed 8 weeks of treatment. Five of the nine patients
      completing the trial were rated as much or very much improved on the clinician
      rated global improvement scale. Self-ratings indicated statistically significant
      improvement on the Illness Attitudes Scales-Total Score (P <.01) and the Beck
      Depression Inventory (P <.04), and there was a trend toward improvement on the
      Whiteley Index (P <.06). The results of this study suggest that nefazodone is a
      promising treatment for hypochondriasis. More extensive evaluation in longer open
      label trials and double-blind, placebo-controlled trials would be warranted.

PMID- 12189255
TI  - Comparison of cognitive impairment associated with major depression following
      stroke versus traumatic brain injury.
AB  - Several studies have reported an association between cognitive impairment and
      major depression following stroke but failed to find a similar association among
      patients with traumatic brain injury (TBI). This study examined the hypothesis
      that age differences between stroke and TBI patients would account for the
      differences in the effect of major depression on cognitive function. We examined
      subjects' cognitive function using the Mini-Mental State Examination and compared
      findings among patients with stroke or TBI. Results indicated that stroke
      patients with major depression (N = 73) were significantly older and more
      cognitively impaired than similar TBI patients (N = 35), even after matching
      patients for lesion volume and years of education. After matching for age,
      however, there was no association of major depression with cognitive impairment
      in this relatively young stroke population. These findings support the hypothesis
      that age, presumably related to physiological response to brain injury, accounts
      for differences in the effect of major depression on cognitive function between
      stroke and TBI patients.

PMID- 12189256
TI  - Depression and anxiety impair health-related quality of life and are associated
      with increased costs in general medical inpatients.
AB  - Two hundred sixty-three consecutive medical inpatients were studied to assess
      whether depression and anxiety are associated with increased costs and reduced
      health-related quality of life. Seventy-three (27.8%) had depressive/anxiety
      disorders, 107 were "subthreshold" cases, and 83 were controls. After adjustment
      for severity of physical illness, using the Duke Severity of Illness Scale, cases
      and subthreshold cases incurred greater mean health care costs than controls over
      the follow-up period: $8,541 (SE = $605) versus $5,857 (SE = $859), P = 0.012.
      There was significant impairment of health-related quality of life (SF36 scores)
      in cases and, to a lesser extent, in subthreshold cases compared to controls.
      This impairment persisted at follow-up, as did anxiety and depression, indicating
      the need for future intervention studies.

PMID- 12189257
TI  - Elevated cholesterol levels associated with nonresponse to fluoxetine treatment
      in major depressive disorder.
AB  - Previous studies have suggested that patients with major depressive disorder may
      have lower cholesterol levels compared to healthy controls. The purpose of this
      study was to examine the relationship between pretreatment serum cholesterol
      levels and clinical response to treatment with fluoxetine among outpatients with
      major depression. Three hundred and twenty-two depressed outpatients meeting DSM
      III-R criteria for major depressive disorder were enrolled in an 8-week, fixed
      dose, open trial of fluoxetine 20 mg/day. Nonfasting serum cholesterol levels
      were obtained for all patients before starting fluoxetine. All patients were drug
      free for a minimum of 2 weeks prior to the onset of the study. Clinical response
      was defined as a 50% or greater decrease in the 17-item Hamilton Rating Scale for
      Depression (HAM-D-17) score at endpoint compared to baseline. Cholesterol levels
      were classified as either elevated (defined as a level equal to or greater than
      200 mg/dL) or nonelevated (defined as a level less than 200 mg/dL). Among the 322
      outpatients, 51.6% were classified as having elevated and 48.4% as having
      nonelevated cholesterol levels at baseline (mean cholesterol level 238.6 +/- 33.4
      mg/dL vs. 170.4 +/- 22.2 mg/dL, respectively). Depressed patients with elevated
      cholesterol levels did not significantly differ in gender ratio but were
      significantly older than depressed patients with nonelevated cholesterol levels
      (P <.0001). After adjusting for age, gender, and Body Mass Index (BMI), depressed
      patients with elevated cholesterol levels were significantly more likely to be
      nonresponders to fluoxetine treatment than were depressed patients with
      nonelevated cholesterol levels (P < 0.05). Elevated serum cholesterol levels
      appear to be associated with poorer response to fluoxetine treatment. Further
      studies are needed to confirm our findings.

PMID- 12189258
TI  - Predicting fatigue and depression in HIV-positive gay men.
AB  - HIV-related fatigue is a prevalent and troubling symptom for HIV-positive people.
      The purpose of the study was to develop a model for predicting fatigue and
      depression among HIV-positive gay men as a function of history of fatigue and
      depression in the previous year and to determine whether psychological and
      psychosocial variables or physiologic variables better predict fatigue. Data from
      96 HIV-positive gay men followed longitudinally for up to 7.5 years were used to
      develop logistic regression models for predicting fatigue and depression. Fatigue
      was predicted by both physiologic and psychological risk factors, whereas
      depression was predicted by only psychological risk factors.

PMID- 12189259
TI  - Male breast cancer: a review of the literature and a case report.

PMID- 12189260
TI  - Untreated celiac disease and development of mental disorders in children and
      adolescents.

PMID- 12189261
TI  - Phenytoin-induced visual disturbances misdiagnosed as alcohol withdrawal.

PMID- 12189262
TI  - Modafinil in the treatment of depression with severe comorbid medical illness.

PMID- 12189263
TI  - Mood and psychotic symptoms with neurocysticercosis.

PMID- 12189264
TI  - Catatonia and liver transplant.

PMID- 12189265
TI  - Near fatal ketoacidosis with olanzapine treatment.

PMID- 12189266
TI  - Argyll-Robertson pupil and neurosyphilis.

PMID- 12189267
TI  - The pain-depression relationship.

PMID- 12189273
TI  - Comparative roles of phospholipase A2 isoforms in cardiovascular pathophysiology.

PMID- 12189274
TI  - Application of data mining for examining polypharmacy and adverse effects in
      cardiology patients.
AB  - This article comments upon the use of data mining tools to examine clinical data.
      Many cardiovascular patients have co-morbid diseases that put them at risk for
      polypharmacy, or severe adverse reactions from the interactions of multiple
      medications. Clinical trials typically use too few patients with stringent
      inclusion/exclusion criteria that prevent an examination of the issue of
      polypharmacy. However, clinical data collected in the course of patient treatment
      can be used in conjunction with data mining to find meaningful results.

PMID- 12189277
TI  - Interaction of xenobiotics with myocardial signal transduction pathways.
AB  - Although the understanding of how toxicants alter cardiac ion-channel function
      has matured rapidly over the past 20-30 yr, little is known about how xenobiotics
      may alter the signaling pathways of cardiac myocyte growth and death. Signaling
      molecules and pathways responsible for the growth of cardiac myocytes include the
      mitogen-activated protein kinases (MAPKs), janus kinase-signal transducer and
      activator of transcription (JAK-STATs), nuclear receptor signaling, calcineurin,
      and the mobilization of free calcium. Signaling molecules and pathways
      responsible for programmed cardiac myocyte death include the death receptors,
      mitochondrial proteins, p53 tumor suppressor protein, ceramide signaling, and
      caspases. Overlap or "crosstalk" between the various growth and death pathways in
      the myocardium is evident, and these pathways likely exist in a delicate balance
      where, for example, slight reductions in growth signaling may favor pathways
      leading to cardiac myocyte apoptosis. Several classical cardiotoxicants are now
      known to alter signaling pathways in cardiac myocytes; however, the significance
      of these effects is not entirely clear. Furthermore, xenobiotics that alter the
      interstitium or extracellular matrix, or both, may significantly alter signaling
      pathways in cardiac myocytes. The goal of this review is to summarize current
      findings regarding the interaction of xenobiotics with myocardial signal
      transduction pathways in the hope of stimulating new insights and highlighting
      important areas for future research.

PMID- 12189278
TI  - Retinoids and cardiovascular developmental defects.
AB  - Vitamin A and related retinoids are critical regulators of normal cardiovascular
      development. Extreme variations in retinoid levels, too little or too much,
      dramatically alter embryonic morphogenesis that has teratogenic consequences,
      including effects on the heart and great vessels. Specific cardiovascular targets
      of retinoid action include effects on the anteroposterior patterning of the early
      heart, left-right decisions and cardiac situs, endocardial cushion formation,
      and, in particular, the neural crest. The cardiovascular defects produced are
      remarkably similar in deficiency and excess, suggesting modulation of common
      developmental or cellular processes by different levels of retinoids. The
      isolation of nuclear receptors that mediate retinoid action has led to the
      identification of some genes directly involved in the regulation of these
      processes and other gene products that may be affected more indirectly. This
      review will examine the mechanism of retinoid action, the requirements for
      vitamin A during normal heart development, and the consequences of nonphysiologic
      or teratogenic exposure.

PMID- 12189279
TI  - Decreased sensitivity of neonatal rabbit sarcoplasmic reticulum to anthracycline
      cardiotoxicity.
AB  - Anthracyclines are useful chemotherapeutic agents whose utility is limited by the
      development of irreversible cardiotoxicity. When tested, the pediatric population
      demonstrates an increased sensitivity to the cardiotoxicity of this class of
      agents, although the reasons for this increased sensitivity are unclear. The
      sarcoplasmic reticulum (SR) is a target for anthracycline cardiotoxicity in
      adults, but the effects of anthracycline on the SR in developing myocardium have
      not been examined. It may be possible to gain insight into the mechanisms of
      cardiotoxicity through a comparative approach. We compared the acute effects of
      doxorubicin, daunorubicin, and caffeine on contractile function in adult and
      neonatal rabbit myocardium. Frequency-dependent contractility, 90% relaxation
      times, and postrest potentiated contractions (a uniquely SR-dependent phenomenon)
      in adult myocardium were inhibited in a concentration- dependent manner. Neonatal
      myocardium, however, was resistant to the effects of these agents. The degree of
      contractile dysfunction was consistent with the difference in SR maturation
      between adult and developing myocardium. Anthracyclines exhibited effects similar
      to those of caffeine, an agent known to render the SR nonfunctional by the
      depletion of the releasable SR calcium pool. These results suggest that
      anthracyclines induce acute cardiac lesions through effects on the SR in adults,
      whereas cardiotoxic effects in the developing myocardium may proceed by a
      different mechanism.

PMID- 12189280
TI  - Selenium supplementation decreases coxsackievirus heart disease during murine
      AIDS.
AB  - Coxsackievirus B3 (CVB3) induces myocarditis, especially in the immunodeficient
      or immature. To investigate whether CVB3 induced pronounced cardiomyopathy during
      the severe immune dysfunction of murine acquired immunodeficiency syndrome
      (AIDS), female C57BL/6 mice were infected with LP-BM5 retrovirus and then
      coinfected with CVB3. C57BL/6 mice, essentially resistant to CVB3-induced
      cardiomyopathy, became susceptible to this cardiomyopathy because of the immune
      dysfunction caused by murine AIDS. This susceptibility suggests that retrovirus
      infection causes conditions favoring the CVB3 induction of cardiac lesions. Mice
      were fed a diet supplemented with selenium (Se) at nine times the recommended
      daily dose for mice (0.933 mg/ kg of diet). Heart tissues were analyzed
      histopathologically 12 d after CVB3 challenge. Mice experiencing concurrent
      retrovirus and CVB3 infection had a high degree of cardiac lesions that were
      consistent with myopathy compared to that in uninfected mice (p < 0.05). Se
      supplementation during murine retrovirus infection significantly diminished the
      pathogenesis caused by concurrent CVB3 infection in mice that had murine AIDS.
      There was a significant increase in the survival of dually retrovirus and CVB3
      infected mice that were fed Se, compared to that of identically treated mice that
      were not fed Se. Hepatic lipid peroxides were significantly diminished in the Se
      supplemented mice as compared to those in immunodeficient mice without
      supplementation (p <F 0.1). Increased oxidation occurred in mice that had murine
      AIDS, which was also shown by reduced tissue vitamin E. Therefore, the reduction
      of retrovirally induced oxidation and inflammation by Se produced conditions that
      improved the survival of mice during CVB3 infection.

PMID- 12189281
TI  - Myocardial toxicity of arsenic trioxide in a mouse model.
AB  - Arsenic trioxide is highly effective in the treatment of acute promyelocytic
      leukemia (APL). In September 2000, the Trisenox brand of arsenic trioxide for the
      treatment of relapsed and refractory APL was approved in the United States. A
      recent clinical report has shown a serious ventricular tachycardia at the
      therapeutic doses of arsenic trioxide in APL patients. The present study was
      undertaken to investigate the cardiotoxic effect of arsenic trioxide using a
      mouse model. Animals were injected intraperitoneally with arsenic trioxide 5 mg/
      kg/d for 30 d, a dose regiment that has been shown to produce plasma
      concentrations of arsenic within the range of those present in arsenic-treated
      APL patients. Analysis of myocardial function revealed that arsenic caused a
      significant decrease in the maximum rate of rise in intraventricular pressure
      during ventricular contraction (MAX dP/dt), and significant increases in the end
      diastolic pressure and ventricle minimum diastolic pressure. In response to B
      adrenergic stimulation by isoproterenol, the arsenic-treated heart did not show
      increase in MAX dP/dt, which was observed as a stress response in the saline
      treated controls. The functional alterations were accompanied by cardiomyopathy,
      as revealed by histopathological and ultrastructural examination. Furthermore,
      arsenic caused myocardial apoptosis, as determined by a terminal deoxynucleotidyl
      transferase-mediated dUTP nick-end labeling assay, which was confirmed by caspase
      3 activation detected by enzymatic assay. Our study thus demonstrates that
      arsenic trioxide, in a dose that could produce clinically comparable serum
      concentrations to those observed in humans, causes cardiotoxicity.

PMID- 12189282
TI  - Improving heart failure care: HCFA reports in.

PMID- 12189283
TI  - Bridging patients to cardiac transplantation.
AB  - Potential recipients of heart transplants have the most advanced form of
      congestive heart failure, in which standard therapy fails to maintain clinical
      stability. In the absence of guidelines derived from evidence obtained in
      clinical trials, caring for these patients becomes a challenge. A successful
      approach requires the proper coordination of surgical and nonsurgical strategies,
      including revascularization and valvular surgery as well as mechanical
      ventricular support and medical strategies. Intensive medical therapy is the most
      commonly used approach for prolonged bridging to transplantation. Although
      carefully individualized regimens are necessary to achieve desired goals, most
      centers adopt a fairly standardized approach involving vasodilators, diuretics,
      and inotropic support. Bridging patients with cardiac decompensation to
      transplantation presents a major therapeutic challenge. Appropriate strategies
      will maximize patients' chances that the bridge from decompensation to
      transplantation remains intact. (c)2000 by CHF, Inc.

PMID- 12189284
TI  - Effects of exercise training on abnormal ventilatory responses to exercise in
      patients with chronic heart failure.
AB  - Patients with chronic heart failure frequently report shortness of breath during
      daily activities as their primary symptom. In recent years, many efforts have
      been made by researchers to explain the mechanisms that underlie the
      characteristic heightened ventilatory response to activity in patients with
      chronic heart failure. The degree to which the ventilatory response to exercise
      is heightened parallels the severity of the disease, and measuring the
      ventilatory gas exchange response to exercise can help quantify the patient's
      response to therapy. Prior to the 1990s, patients with chronic heart failure were
      generally discouraged from participating in programs of exercise training.
      However, in the last decade, studies have demonstrated that exercise training is
      quite safe for these patients, and a multitude of benefits have been reported.
      Among the benefits of training are improvements in the abnormal ventilatory
      response to exercise. Although many mechanisms could potentially explain this
      response, it appears most likely that this improvement after training is due to a
      reduction in lactate accumulation and an attenuation of the heightened muscle
      receptor reflex response that occurs in chronic heart failure. This article
      reviews the mechanisms of dyspnea in chronic heart failure, along with recent
      studies assessing the effects of training on abnormal ventilatory responses to
      exercise in these patients. (c)2000 by CHF, Inc.

PMID- 12189285
TI  - Simple methods of assessing physical activity in patients with chronic heart
      failure.
AB  - This article reviews simple, noninvasive ways to assess physical activity in
      patients with chronic heart failure. Six- or 9-minute walk tests appear to be
      useful not only for selecting patients with relatively advanced heart failure but
      also as prognostic screening tests. The Master-Borg test (Master's two-step
      testing and 10-point Borg scale) is useful for assessing symptoms during
      exercise. Weekly pedometer counts show that the level of activity in patients
      with heart failure is dramatically less than in healthy controls. Physical
      activity can be determined directly by an ambulatory calorie counter that
      measures step scores and energy expenditure using specific accelerometers.
      Careful clinical interviewing regarding symptoms, together with submaximal
      exercise testing and use of motion sensors, are recommended as useful, simple,
      noninvasive alternatives for assessing physical activity in this patient
      population. (c)2000 by CHF, Inc.

PMID- 12189286
TI  - The oxygen uptake efficiency slope and its value in the assessment of
      cardiorespiratory functional reserve.
AB  - Oxygen uptake efficiency slope is a new index of cardiorespiratory functional
      reserve derived from the logarithmic relation between oxygen uptake (VO(2)) and
      minute ventilation during incremental exercise. The oxygen uptake efficiency
      slope represents how effectively oxygen is extracted and taken into the body from
      the air, and then ventilated. The physiologic backgrounds of the index are based
      on: 1) the development of metabolic acidosis that is controlled by the
      distribution of blood to the skeletal muscles; 2) the physiologic dead space that
      is affected by the perfusion to the lungs; and 3) arterial carbon dioxide partial
      pressure. One of the greatest advantages of the oxygen uptake efficiency slope is
      that it can be calculated by exercise data of submaximal levels. Another
      advantage is that it is mathematically determined from a set of gas analysis data
      and, therefore, is completely an objective measurement. Moreover, the oxygen
      uptake efficiency slope is shown to be highly reproducible. Clinical applications
      of the oxygen uptake efficiency slope have been reported initially from a
      population of pediatric patients with heart disease, then from adult patients
      with chronic heart failure, and finally from elite endurance athletes. Further
      applications are expected with the use of this sophisticated index. (c)2000 by
      CHF, Inc.

PMID- 12189287
TI  - Circulatory assist devices 2000: an update.
AB  - Mechanical circulatory assist devices have been used in clinical practice as a
      bridge to transplantation since the late 1960s. In 1982, the first totally
      artificial heart designated as permanent therapy was implanted, but relatively
      few totally artificial hearts are implanted today. In the last several years,
      there has been a shift toward the use of left ventricular assist devices as a
      bridge to cardiac transplantation. Likewise, there is increasing interest in the
      use of ventricular assist devices as a bridge to recovery for patients with
      myocarditis, dilated cardiomyopathy, and following myocardial infarction or
      cardiotomy. This review presents basic information on the present use of these
      devices as they relate to transplantation and recovery, and as permanent therapy.
      Individual devices will briefly be described, as will indications for, and timing
      of, implantation. Other related issues, such as right heart failure, pulmonary
      hypertension, arrhythmias, anticoagulation, and infections, will be addressed. In
      closing, the future of mechanical circulatory devices will be discussed. (c)2000
      by CHF, Inc.

PMID- 12189288
TI  - Pharmacotherapy in congestive heart failure: COX-2 inhibition: a cautionary note
      in congestive heart failure.
AB  - NSAIDs have been a mainstay of therapy for rheumatologic diseases for a number of
      years. Unfortunately, their use was accompanied by sometimes unacceptable
      gastrointestinal and/or renal side effects. Therefore, safer treatment options
      were sought. In the process of such a search, selective cyclo-oxygenase-2
      inhibitors were identified. Drugs in this class have anti-inflammatory properties
      similar to NSAIDs and did not produce anywhere near the same pattern of NSAID
      related gastrotoxicity. The enthusiasm for this class of drugs would appear, at
      least on the surface, to be well grounded. However, establishing the renal side
      effect profile of the selective cyclo-oxygenase-2 inhibitors would appear to be a
      work in progress. Formal studies with selective cyclo-oxygenase-2 inhibitors have
      not been conducted in the congestive heart failure population. Information does
      though exist for other patient cohorts--similarly "prostaglandin-dependent" for
      their integrity of renal function, such as the elderly and sodium-deplete
      individual. These data would strongly suggest that the selective cyclo-oxygenase
      2 inhibitors could decrease glomerular filtration rate and stimulate salt and
      water retention, comparable to what occurs with nonselective NSAIDs. To date, no
      compelling information exists, which supports the notion that differences exist
      among the currently available selective cyclo-oxygenase-2 inhibitors--celecoxib
      and--in the potential to negatively impact renal function in this and similarly
      compromised patient populations. (c)2000 by CHF, Inc.

PMID- 12189289
TI  - Difficult cases in heart failure: Effective treatment of severe acute myocarditis
      with intravenous immune globulin and pulse corticosteroids in a 32-year-old
      patient.
AB  - We describe a 32-year-old patient with acute myocarditis resulting in severe
      heart failure with hemodynamic compromise who improved significantly after
      treatment with immune globulin and pulse steroids. Six weeks after termination of
      the immunosuppressive therapy the patient developed symptoms of heart failure
      again and his ejection fraction decreased to 30%-34%. Treatment with immune
      globulin resulted in resolution of symptoms and return of left ventricular
      function. (c)2000 by CHF, Inc.

PMID- 12189290
TI  - Medicare initiatives to improve heart failure care: an introduction.
AB  - Purchasers of health care, patients, physicians, and other health care
      professionals are increasingly seeking to evaluate quality of health care.
      Scattered reports have suggested that there is currently marked variation in
      evaluation and treatment of heart failure and substantial gaps between guideline
      recommendations and care delivered to heart failure patients. Heart failure is
      the most common discharge diagnosis for Medicare beneficiaries and yet, until
      recently, relatively little national information was available to describe the
      quality of care and to identify opportunities to improve practice. To address the
      need to evaluate care of patients with heart failure and support national, state,
      and local efforts to improve care and outcomes, the Health Care Financing
      Administration has initiated three programs that stretch across much of the
      continuum of care: the National Heart Failure Quality Improvement Project,
      focusing on inpatient care; the Heart Failure Practice Improvement Effort (HF
      PIE), a pilot outpatient effort in 11 states; and the 2001 requirement for
      Medicare+Choice Organizations to initiate quality improvement efforts for their
      heart failure patients. This paper is the first in a series that will provide
      information about these programs. We hope that this series will stimulate
      discussion on how clinicians can join these national efforts to improve the care
      and outcomes of patients with heart failure. (c)2000 by CHF, Inc.

PMID- 12189291
TI  - Frontiers in congestive heart failure: Comparison of echocardiography and
      electron beam tomography in differentiating the etiology of heart failure.

PMID- 12189292
TI  - Frontiers in congestive heart failure: Tachycardia-related cardiomyopathy: a
      common cause of ventricular dysfunction in patients with atrial fibrillation
      referred for atrioventricular ablation.

PMID- 12189293
TI  - Types of anesthesia and cardiovascular outcomes in patients with congestive heart
      failure undergoing vascular surgery.
AB  - BACKGROUND. Whether regional anesthesia is preferable to general anesthesia for
      patients with congestive heart failure (CHF) undergoing noncardiac surgery
      remains controversial. The purpose of this study was to determine whether
      anesthetic technique affects postoperative cardiac outcome in patients with CHF;
      we hypothesized that cardiac outcomes would be superior with regional anesthesia
      compared with general anesthesia. DESIGN. 106 patients with prior or persistent
      CHF, undergoing femoral to distal artery bypass surgery, were randomized to
      general anesthesia (29 patients) or regional anesthesia (epidural, 42 patients,
      or spinal anesthesia, 35 patients). The primary end point was death or adverse
      cardiac events (myocardial infarction, unstable angina, or CHF). RESULTS. There
      was no statistically significant difference between groups in incidence of
      combined cardiac events, death, myocardial infarction, death or myocardial
      infarction combined, unstable angina, or CHF. CONCLUSION. Although larger studies
      are required to establish equivalence of the anesthetic strategies, this large
      single center study preliminarily indicates that regional anesthesia may not be
      superior to general anesthesia in patients with heart failure undergoing femoral
      to distal artery bypass surgery. (c)1999 by CHF, Inc.

PMID- 12189294
TI  - The renin angiotensin system and endothelial dysfunction in chronic heart
      failure: role of endogenous fibrinolysis.
AB  - Regulation of vascular tone by the endothelium is abnormal in patients with heart
      failure and contributes to the characteristic peripheral vasoconstriction and
      increased afterload. This endothelial dysfunction is mediated through several
      endothelium-derived factors, including nitric oxide; there is an important
      interplay between the endothelium and the renin angiotensin system. The benefits
      of ACE inhibition in heart failure relate, in part, to a reduction in ischemic
      events which may be mediated by improvements in endothelial function and the
      endothelium derived fibrinolytic parameters: tissue plasminogen activator (t-PA)
      and its inhibitor, plasminogen activator inhibitor type 1 (PAI-1). In addition to
      potential improvements in the regulation of vasomotion, ACE inhibitor therapy may
      increase bradykinin induced t-PA release and/or reduce angiotensin II mediated
      PAI-1 release. Recent evidence suggests that both angiotensin II type 1 receptor
      (AT(1)) antagonism and ACE inhibition improve basal fibrinolytic parameters in
      patients with heart failure which may facilitate the acute endogenous
      fibrinolytic response. 1999 by CHF, Inc.

PMID- 12189295
TI  - Clinical epidemiology of heart failure.
AB  - Heart failure (HF) is rapidly becoming one of the most prevalent cardiovascular
      disorders; the incidence of HF is expected to continue to increase in the years
      to come. The peculiarities of the syndrome require special approaches from the
      point of view of both clinical management and research methodology. As far as
      clinical management, new models based on a multidisciplinary approach and
      continuity of care should be implemented. The methodology of epidemiological
      research should take into account the complexity of the syndrome, the high
      frequency of comorbid conditions, the advanced age of typical patients, and the
      spreading of HF patients among different health care providers and specialists.
      In this paper, a general epidemiological view of HF is reported and studies of
      clinical epidemiology carried out in Italy in the area of HF are described. (c)
      1999 by CHF, Inc.

PMID- 12189296
TI  - Cardiac chaos: implications for congestive heart failure.
AB  - Cardiac chaos is an emerging paradigm in cardiology that may prove useful in the
      management of patients with congestive heart failure (CHF). In short, cardiac
      chaos refers to the minute-yet seemingly purposeful-fluctuations in the
      instantaneous heart rate or interbeat interval. Recent studies have demonstrated
      that cardiac chaos accounts for much of the beat-to-beat variability of the heart
      rate in healthy subjects, but the cardiac chaos appears to subside in patients
      with CHF. This brief review gives an overview of the background and current
      understanding about cardiac chaos and its relation to heart rate variability
      (HRV). Practical considerations on the measurement of cardiac chaos and its
      clinical application are discussed. (c) 1999 by CHF, Inc.

PMID- 12189297
TI  - Diagnosis and assessment in heart failure.
AB  - Heart failure is a common and growing problem. Its optimal and effective
      management and the evaluation of new therapies require assessment of underlying
      etiology, type of cardiac dysfunction, severity, prognosis, and response to
      therapy. Unfortunately, the lack of a universally agreed definition of heart
      failure and uniform criteria make an accurate and complete diagnosis of heart
      failure difficult. Currently, a wide range of investigations and assessments is
      available, including assessment of symptoms, exercise performance, and cardiac
      function. In particular, left ventricular (LV) ejection fraction (EF) is widely
      used and a good marker of the severity of LV dysfunction and prognosis. It is now
      being recognized that the early identification and treatment of patients with
      asymptomatic LV dysfunction may prevent subsequent progression to symptomatic
      heart failure. Recently, attention has focused on the neurohormonal activation
      that occurs early in heart failure, and especially increasing evidence suggests
      that plasma levels of neurohormones and brain natriuretic peptides, may be useful
      biochemical markers in the diagnosis and assessment of heart failure at an early
      stage. Further evaluation of this neurohormonal activation and treatments
      directed towards it may provide considerable benefits in improving patient
      morbidity and mortality. (c)1999 by CHF, Inc.

PMID- 12189299
TI  - Frontiers in congestive heart failure: Comparison of candesartan, enalapril, and
      their combination in congestive heart failure-Randomized Evaluation of Strategies
      for Left Ventricular Dysfunction (RESOLVED) pilot study.

PMID- 12189300
TI  - Frontiers in congestive heart failure: Pacemakers for refractory heart failure
      the road not taken.

PMID- 12189298
TI  - Difficult cases in heart failure: Role of continuous ambulatory peritoneal
      dialysis in refractory heart failure.
AB  - Continuous ambulatory peritoneal dialysis (CAPD) offers a new modality for use in
      the treatment of refractory congestive heart failure (CHF). Although the use of
      peritoneal dialysis to treat refractory heart failure is not new, improved
      understanding of the physiology and technique of this system has allowed its use
      over prolonged periods of time. The application of continuous peritoneal dialysis
      to the cardiac patient changes its scope considerably. When combined with current
      medical treatment, it removes fluid volume effectively and safely providing the
      best possibility for prolonged medical improvement. Continuous ambulatory
      peritoneal dialysis should be considered in patients with biventricular failure
      who have associated comorbidities like pulmonary hypertension and progressive
      renal insufficiency. We report the management of two such patients with NYHA
      Class IV heart failure who had become unresponsive to maximum pharmacological
      management and developed prerenal dialysis and during the 6 month follow up
      remained on dialysis without developing any significant complications and
      improved to NYHA class I. (c)1999 by CHF, Inc.

PMID- 12189301
TI  - Intravenous therapy for chronic heart failure exacerbations.
AB  - Chronic heart failure (HF) will be the disease of the new millennium. The last
      decade has seen major developments in the management of HF, with beta-blockers
      and ACE inhibitors becoming the cornerstones of therapy by virtue of the
      reductions in total mortality. However, significant gaps remain. Hospitalization
      for exacerbations of HF are frequent and account for more than 6 million hospital
      days from this disease related group. Although a variety of intravenous (IV)
      agents are available for the management of exacerbations of HF, readmission rates
      are as high as 20%-47% at 6 months. Acute IV therapy for acute decompensation of
      chronic HF consists of inotropic agents most of which also have vasodilator
      properties, vasodilator, and diuretics. In addition, there are newer agents in
      various developmental stages, especially, calcium sensitizing drugs, vasopressin
      receptor antagonists, and natriuretic peptides. Despite the multiplicity of
      agents, there are no well designed, randomized, placebo controlled trials to
      guide IV inpatient therapy for HF exacerbations. (c)1999 by CHF, Inc.

PMID- 12189302
TI  - Coronary flow reserve of nonischemic heart failure.
AB  - Coronary flow reserve (CFR) provides essential information about the coronary
      microvascular bed in the absence of narrowing of epicardial coronary arteries.
      Experimental and human data suggest chronic heart failure is associated with a
      reduction of CFR in the absence of coronary artery disease. Dipyridamole,
      papaverine, or adenosine administration intravenously or intracoronary achieve
      maximal vasodilation of coronary arteries in human studies, however, systemic
      administration of vasodilator (dipyridamole) resulted in conflicting effects on
      systemic blood pressure. Various mechanisms including the nitric oxide pathway,
      neurohumoral alterations, and microvascular spasm among others, may contribute to
      the decrease in CFR in nonischemic heart failure. Notably, there is no study
      which describes the correlation between subjective symptoms of heart failure and
      the severity of the decrease in CFR. Further investigation of this area may be
      beneficial in determining the appropriate level of exercise training for heart
      failure patients and understanding mechanisms of the progression of heart
      failure. (c)1999 by CHF, Inc.

PMID- 12189303
TI  - Dopamine and congestive heart failure: pharmacology, clinical use, and
      precautions.
AB  - It has been suggested that low dose dopamine (<5 micro g/kg/min) may have renal
      protective effects. There are, however, no randomized, double blind, placebo
      controlled studies to support these observations. The contribution of
      improvements in cardiac output (due to beta(1)-adrenergic stimulation) to
      increases in renal blood flow, independent of changes in renal vasodilation, are
      unclear. There is little evidence to support any dopamine induced clinically
      significant improvement in renal function in the presence of diuretics. Given the
      limited evidence of benefits of low dose dopamine, potential adverse effects need
      to be recognized, particularly in patients with heart failure. Low dose dopamine
      induces hypoxemia in patients with heart failure by impairing both gas exchange
      and ventilatory responses and thus could precipitate respiratory decompensation
      in patients being weaned from ventilators. Sleep disordered breathing is highly
      prevalent in heart failure patients-the effects of dopamine induced chemoreflex
      inhibition may prove deleterious in this condition. We therefore believe that
      current knowledge of the risk/benefit ratio of the use of "renal doses" of
      dopamine does not support its widespread use in patients with heart failure,
      particularly in those patients in whom respiratory function is compromised.
      (c)1999 by CHF, Inc.

PMID- 12189304
TI  - Cyclooxygenase-2 and nuclear factor-kappaB in myocardium of end stage human heart
      failure.
AB  - Over the past three decades, numerous studies have shown diverse functional and
      morphological effects for prostanoids on cardiac myocytes with levels of
      prostanoids elevated in congestive heart failure. We examined the expression of
      cyclooxygenase-2 (COX-2) and activation of nuclear factor-kappaB (NF-kappaB) in
      failing human hearts. Expression of COX-2 and activation of NF-kappaB were
      examined in myocardial tissues from 27 patients with end stage heart failure, 2
      septic patients, and 8 normal control subjects. There was little or no expression
      of COX-2 and NF-kappaB in the control hearts. There was abundant expression of
      COX-2 mRNA and protein in myocytes and inflammatory cells in areas of fibrotic
      scar compared with regions of normal morphology in all cases of heart failure,
      except in the cases with sepsis which showed abundant COX-2 throughout the
      myocardium. Sites of NF-kappaB activation were associated with those of COX-2
      expression. We concluded that COX-2 expression and NF-kappaB activation are
      elevated in patients with congestive heart failure. Cellular induction of both
      molecules is associated with sites of inflammation and scar formation. (c)1999 by
      CHF, Inc.

PMID- 12189305
TI  - Pharmacotherapy in congestive heart failure: Do NSAIDs attenuate the therapeutic
      effect of ACE inhibitors in heart failure patients?
AB  - Heart failure (HF) is a disease which is prevalent in the elderly. Concomitant
      rheumatological diseases are also prevalent in this population which require
      treatment with NSAIDs. Aspirin is also routinely used for the primary and
      secondary prevention of coronary artery disease (CAD) which is a common cause of
      HF. ACE inhibitors are the cornerstone of drug therapy in managing patients with
      HF. Elderly patients with HF are frequently encountered with multiple drug
      therapy, such as nonsteroidal antiinflammatory drugs (NSAIDs) including aspirin
      and ACE inhibitors. In recent years there has been a concern of negative
      interaction between these two common drug therapies in patients with HF which may
      subsequently attenuate the beneficial effects of ACE inhibitors. Whereas some
      studies have shown that the coadministration of NSAIDs including aspirin with ACE
      inhibitors might diminish the degree of improvement in cardiovascular
      hemodynamics and adversely affect renal functions, other studies have failed to
      substantiate this. Furthermore, although potential opposing effects of NSAIDs and
      ACE inhibitors on prostaglandin synthesis has been cited as the mechanism
      responsible for the negative interactions, more work is needed in this area to
      better define the precise reasons responsible for it. However, based on the
      available data thus far, it is prudent to be aware of such negative interaction
      and especially in case of aspirin to avoid it by using relatively lower dosage.
      (c)1999 by CHF, Inc.

PMID- 12189306
TI  - Difficult cases in heart failure: Atrioventricular interval optimization
      utilizing thoracic electrical bioimpedance.
AB  - The authors describe the use of thoracic electrical bioimpedance, a noninvasive,
      simple, low risk technique to optimize atrioventricular delay in a patient with a
      dual chamber pacemaker, right ventricular infarct, and symptoms NYHA functional
      class III-IV. Optimization of the atrioventricular interval was associated with
      improvement of hemodynamic parameters and resolution of the symptoms of heart
      failure. The application of noninvasive hemodynamic parameters might have a great
      deal of impact in the management of patients with several cardiovascular
      diseases. Multicenter studies are underway. (c)1999 by CHF, Inc.

PMID- 12189307
TI  - Oxidative stress and congestive heart failure.
AB  - Oxygen free radicals, produced by the reduction of oxygen during many cellular
      reactions, have been implicated in the pathogenesis of a variety of
      cardiovascular diseases. Extremely reactive, free radicals damage many cellular
      structures and interfere with multiple cell functions. Clinically, free radicals
      have been associated with coronary atherosclerosis, ischemia, and reperfusion
      injury ("stunning"), and other processes related to chronic myocardial
      dysfunction. Several studies have reported elevated markers of free radical
      mediated injury in patients with congestive heart failure (CHF), and the link
      between oxidative stress and the genesis and progression of chronic CHF is being
      increasingly explored. This review briefly highlights free radical biology and
      examines the rationale and evidence for the role of oxidative stress in chronic
      heart failure. (c)1999 by CHF, Inc.

PMID- 12189308
TI  - Implementation of a multidisciplinary disease management program for heart
      failure patients.
AB  - Institutions across the country are considering the feasibility of a disease
      management program for heart failure (HF) patients. Published reports suggest
      that such programs can save money and improve outcomes. However, the design of a
      disease management program can be challenging. This paper describes the structure
      and function of a successful disease management program for heart failure
      patients. The program is supported by a multidisciplinary team of nurses,
      pharmacists, dietitians, social workers, and physicians who approach the problem
      from a self care perspective. Program components include standardized educational
      materials, reinforcement of educational contacts, monthly support groups, and a
      quarterly newsletter. Existing staff built the program with few additional
      resources and staff. The program, which costs only approximately $330/patient for
      a 6 month intervention, has decreased hospital readmissions (29%) and days in the
      hospital (43%) significantly. (c)1999 by CHF, Inc.

PMID- 12189309
TI  - Atrial natriuretic peptides in the diagnosis and treatment of congestive heart
      failure.
AB  - Atrial natriuretic peptides (ANPs) consist of a family of peptides (atrial
      natriuretic factor [ANF], long acting natriuretic peptide, vessel dilator,
      kaliuretic peptide, urodilatin, brain natriuretic peptide [BNP], and C type
      natriuretic peptide [CNP]) which are synthesized within the heart, except for
      urodilatin. Of these natriuretic peptides, the vessel dilator radioimmunoassay
      (RIA) of a single plasma sample is the most sensitive and specific in the
      diagnosis of early (i.e., NYHA class I) congestive heart failure (CHF). Vessel
      dilator is beneficial in the treatment of CHF, enhancing of urine flow two- to 13
      fold and sodium excretion three- to four-fold for 3 hours after stopping its
      infusion. This 37 amino acid peptide hormone simultaneously decreases systemic
      vascular resistance 24%, pulmonary vascular resistance 25%, pulmonary capillary
      wedge pressure 33%, and central venous pressure 27% while increasing cardiac
      output 34%, cardiac index 35%, and stroke volume index 24% in individuals with
      CHF. (c)1999 by CHF, Inc.

PMID- 12189310
TI  - Difficult cases in heart failure: Reversible heart failure secondary to
      thyrotoxicosis.
AB  - Perhaps one of the most important steps in caring for a patient with heart
      failure is seeking a reversible form of heart failure. Often addressing a disease
      process, like myocardial ischemia or systemic hypertension, rapidly attenuates
      the progressive natural history of left ventricular dysfunction. Beyond the usual
      reversible causes, however, are some that may be overlooked. This case provides
      an insight into one of these causes. (c)1999 by CHF, Inc.

PMID- 12189311
TI  - Frontiers in congestive heart failure: Effect of Metoprolol CR/XL in chronic
      heart failure: Metoprolol CR/XL Randomised Intervention Trial in Congestive Heart
      Failure (MERIT-HF).

PMID- 12189313
TI  - Heart failure monitoring: innovation awaits.

PMID- 12189312
TI  - Frontiers in congestive heart failure: Newer drug therapy for congestive heart
      failure.

PMID- 12189314
TI  - Electronic home monitoring of congestive heart failure patients: design and
      feasibility.
AB  - The efficacy of electronic monitoring in the home care of heart failure (HF)
      patients has not been widely reported. We developed a Vital Sign System (VSS)
      monitoring device capable of measuring the weight, blood pressure, and heart rate
      of congestive heart failure (CHF) patients in the home and transmitting these
      measurements via modem to a World Wide Web server. In this study of 22 CHF
      patients, we tested the reliability of the VSS electronic measurements compared
      to manual measurements taken by visiting home care nurses and ease of use of the
      VSS units as rated by both patients and home care nurses. The correlation of
      electronic to manual measurements was high (weight r=0.99; systolic blood
      pressure [SBP] r=0.84; diastolic blood pressure [DBP] r=0.54; heart rate [HR]
      r=0.88). The mean difference between electronic and manual measurements was
      within an acceptable range for clinical surveillance and care of CHF patients
      (weight 1.6 lbs; SBP 8.8 mm Hg; DBP 9.2 mm Hg; HR 0.7 bpm) The devices were rated
      favorably by both nurses and patients. The VSS monitoring device is a reliable,
      feasible, and favorably rated technology for home surveillance of CHF patients.
      (c)1999 by CHF, Inc.

PMID- 12189315
TI  - Monitoring skeletal muscle oxygenation during exercise by near infrared
      spectroscopy in chronic heart failure.
AB  - Patients with chronic heart failure (HF) have a reduced skeletal muscle blood
      flow which can in part explain reduced exercise tolerance and increased
      ventilation. All the techniques commonly employed to measure skeletal muscle
      blood flow have limitations that reduce their accuracy and clinical application.
      Near infrared spectroscopy (NIRS) is a noninvasive, inexpensive, and reproducible
      technique able to monitor muscle oxygenation both at rest and during exercise,
      providing information about tissue perfusion. The principle of NIRS is based on
      the observation that the light absorption characteristics of hemoglobin (Hb) and
      myoglobin (Mb) in the near infrared region (700-1000 nm) change depending on
      their relative saturations. In humans, NIRS has been employed to monitor skeletal
      muscle oxygenation during exercise and/or after cuff-induced limb ischemia in
      normal subjects as well as patients with chronic HF. Patients with chronic HF
      have a reduced Hb/Mb oxygenation at any matched work rate and a more rapid
      deoxygenation above the anaerobic threshold than normal subjects. More recently,
      NIRS has been used to determine the kinetics of muscle oxygenation in recovery
      after constant work rate exercise, providing evidence of an inverse relation with
      cardiac function as assessed by peak oxygen uptake. In conclusion, NIRS appears
      to be a new promising noninvasive technique for studying muscle oxygenation in a
      variety of experimental models. (c)1999 by CHF, Inc.

PMID- 12189316
TI  - Role of dopamine in congestive heart failure: a contemporary appraisal.
AB  - The pharmacodynamic effects of dopamine, an endogenous catecholamine, are complex
      and mediated through selective activation of specific dopaminergic and adrenergic
      receptors in a dose dependent manner. Low dose dopamine (0.5-2 micro g/kg/min)
      induces intrarenal vasodilatation, augmented renal blood flow, and inhibition of
      renal tubular sodium reabsorption through direct stimulation of peripheral
      dopaminergic receptors DA1 and DA2. Intermediate doses (3-10 micro g/kg/min)
      favor beta(1)-adrenergic receptor stimulation of the heart and peripheral
      vasoconstriction due to alpha-adrenergic receptor stimulation. At higher does
      (>10 micro g/kg/min), an elevated systemic vascular resistance prevails and the
      salutary effect on renal blood flow is diminished or lost. Dopamine is no longer
      favored as a first line agent for use in congestive heart failure (CHF) owing to
      the superior pharmacodynamic properties of dobutamine and is more properly used
      as an agent for vasopressor therapy. Studies have not supported the renal sparing
      effect of low dose dopamine for critically ill patients with incipient or
      established acute renal failure due to ischemia or nephrotoxicity. Evidence that
      low dose dopamine protects renal function during vigorous diuresis for CHF
      associated with renal insufficiency has clinical support and a rationale for its
      use. (c)1999 by CHF, Inc.

PMID- 12189317
TI  - Pharmacotherapy in congestive heart failure: Effect of the insertion/deletion
      polymorphism of the ACE gene on response to ACE inhibitors in patients with heart
      failure.
AB  - The renin angiotensin aldosterone (RAA) axis is a common target for pharmacologic
      intervention in the treatment of hypertension, renal disease, and/or congestive
      heart failure (CHF). ACE inhibitors have increasingly been used in an effort to
      disable this neurohumoral system. Despite the almost elegant logic of this
      therapeutic approach it has not always proven uniformly successful. The fairly
      diverse response to ACE inhibitor therapy in CHF has been ascribed to a number of
      pharmacokinetic and pharmacodynamic considerations and most recently to a genetic
      polymorphism for ACE. The presence of a DD insertion/deletion pattern for ACE
      seems to predict an increased level of ACE, possibly increased angiotensin II
      concentrations, and a relative resistance to the hemodynamic effects of ACE
      inhibitors. The frequency of the particular insertion/deletion pattern in CHF is
      not known. Whether the particular insertion/deletion pattern of a patient will
      determine whether a patient receives angiotensin receptor antagonist therapy
      rather than ACE inhibitor treatment remains to be determined. (c)1999 by CHF,
      Inc.

PMID- 12189318
TI  - Difficult cases in heart failure: Left ventricular assist device implantation for
      the treatment of recurrent ventricular tachycardia in end stage heart failure.
AB  - The authors describe the surgical implantation of a left ventricular assist
      device (LVAD) in a patient with ischemic cardiomyopathy and recurring episodes of
      ventricular tachycardia with associated sudden death, as a therapeutic
      intervention for the recurrent ventricular arrhythmias. The clinical inference of
      this report demonstrates that these devices are useful as a bridge to heart
      transplantation, not only improving the symptoms of heart failure but also
      suppressing malignant ventricular arrhythmias. (c) 1999 by CHF, Inc.

PMID- 12189319
TI  - Frontiers in congestive heart failure: Beta-adrenergic blocking agent use and
      mortality in patients with asymptomatic and symptomatic left ventricular systolic
      dysfunction: a post hoc analysis of the Studies of Left Ventricular Dysfunction.

PMID- 12189320
TI  - Frontiers in congestive heart failure: Tolerability and efficacy of carvedilol in
      patients with New York Heart Association class IV heart failure.

PMID- 12189321
TI  - Pulsed inotropic therapy: an evangelical haven or justified sanctuary.

PMID- 12189323
TI  - Selective treatment for heart failure: the future beckons?
AB  - Myocardial failure results from a variety of insults yet treatments have been
      given in a nonselective way. The benefits of treatments on symptoms are not
      related to etiology, but there is increasing evidence that prognosis is. Whenever
      the prognostic benefits of treatments have been classified according to etiology,
      patients with myocardial damage without concomitant ischemic heart disease fare
      better. In this paper, we present and evaluate the data on prognosis and discuss
      the possible reasons behind these differences. These differences are important
      because they will help to inform patients and physicians about prognosis based on
      the underlying cause of myocardial damage. In the future, treatment may be more
      successful if it is targeted to patients according to the cause of heart failure.

PMID- 12189322
TI  - An overview of intermittent inotropic therapy for severe congestive heart
      failure.
AB  - Congestive heart failure (CHF) is a major problem in the field of medicine in the
      U.S. Over 4 million people in the U.S. have CHF with 400,000 new cases per year.
      This diagnosis creates 6 million hospital days with a Medicare cost of billions
      of dollars. There are limited options for patients >65 years of age who have
      resistant heart failure on maximum medical therapy. There is considerable debate
      surrounding intermittent inotropic therapy. This paper is a review of the
      literature regarding this form of therapy; 20 studies are described. All but one
      of these studies disclose beneficial effects. The major criticism of these
      studies is that they are small and not randomized or placebo controlled. Larger
      well controlled studies are needed to determine the effect and safety of this
      treatment. Researchers must develop and evaluate all forms of therapy fairly to
      help decrease hospitalizations, decrease mortality, and improve quality of life.

PMID- 12189325
TI  - Pharmacotherapy in congestive heart failure: Cardiopulmonary effects of
      ophthalmically administered beta-blockers.
AB  - Early clinical studies reported that timolol and other topical beta-blockers were
      effective in reducing intraocular pressure, without the side effects associated
      with other antiglaucoma agents. However, because people with cardiovascular or
      respiratory diseases were generally excluded from many of these early studies,
      the risk of serious cardiovascular and respiratory side effects was seriously
      underestimated. Once these drugs were made available to the general population,
      reports of systemic side effects began to proliferate. Very quickly adverse
      effects from topical beta-blockade became "old news." Despite this new found
      recognition, many treating physicians still remained unaware of the potential for
      systemic beta-blockade from topical applied beta-blockers. A significant portion
      of a topically administered dose of a beta-blocker can be absorbed and thereby
      effect systemic beta-blockade. Sensitivity to systemic beta-blockade can be quite
      dramatic in certain highly susceptible patients, particularly those with either
      cardiac or pulmonary abnormalities. Careful review of patients' medications will
      generally lessen, but not completely eliminate, the risk of undesired
      complications attributable to topical beta-blockade.

PMID- 12189324
TI  - Ventricular function following drug-induced regression of hypertensive left
      ventricular hypertrophy.
AB  - Drug-induced regression of left ventricular hypertrophy (LVH) due to arterial
      hypertension is generally accompanied by improved cavity filling because of
      changes in the structural and functional determinants of diastolic efficiency. In
      hypertensive patients in whom regression of LVH is achieved, systolic function
      also improves in the long term, at least when the therapeutic drug used is an ACE
      inhibitor. That the return to pretreatment blood pressures which occurs upon
      sudden withdrawal of medication is not accompanied by similar deterioration of
      ventricular function suggests regression of histological remodeling (i.e., not
      only a reduction in myocyte and interstitial volume, but also the amelioration of
      endothelial dysfunction and structural alterations in coronary microcirculation).

PMID- 12189326
TI  - Difficult cases in heart failure: Importance of patient selection in the use of
      intermittent inotrope infusions for advanced heart failure.
AB  - Intermittent infusions of inotropes have been used with increasing frequency for
      patients with advanced heart failure (HF). The use of intermittent inotrope
      infusions remains controversial for several reasons. However, the effect, either
      positive or negative, of intermittent inotropes in refractory unstable HF
      patients is not well studied. While prior experience with chronic oral inotropes
      in stable, advanced HF raises substantial concerns, it may not be directly
      applicable to a critical evaluation of intermittent inotrope infusions in
      unstable patients. Further study demonstrating the safety and efficacy of this
      approach in these patients is imperative. The uncertainties surrounding this
      therapy, mandate the selection of appropriate candidates be made with substantial
      care. We report three patients with advanced HF despite conventional therapy, in
      whom intermittent inotropes were considered. These cases illustrate that this
      therapy can be avoided in many patients by acceleration of conventional
      medications, patient education, and aggressive follow up intermittent. However,
      outpatient inotrope infusions may be helpful in highly selected patients with
      refractory, unstable HF.

PMID- 12189327
TI  - Frontiers in congestive heart failure: Prolonged beneficial effects of a home
      based intervention on unplanned readmissions and mortality among patients with
      congestive heart failure.

PMID- 12189328
TI  - Frontiers in congestive heart failure: Sympathetic activation in heart failure
      and its treatment with beta-blockade.

PMID- 12189329
TI  - Systolic dysfunction of the ventricle in congestive heart failure:
      pathophysiology, diagnosis, and therapy.
AB  - Investigations into the pathophysiology and treatment of the failing left
      ventricle have yielded impressive results over the past three decades. Patients
      with systolic dysfunction have abnormalities of the molecular machinery and
      signaling of contraction which may be in-born or acquired, and result in the
      characteristic mechanical abnormalities associated with this condition.
      Correlation of these ultrastructural contractile abnormalities with the
      mechanical dysfunction observed clinically is complicated by alterations of
      preload and afterload which accompany systolic failure. The systemic consequences
      of contractile failure result in a cascade of neuroendocrine and cytokine
      activation which perpetuates a cycle of further myocardial dysfunction and
      systemic humoral response. Based on this neuroendocrine paradigm, pharmacologic
      intervention trials have yielded promising gains in survival and symptom status
      in patients with systolic dysfunction, particularly with the ACE inhibitors and
      the beta-adrenergic blockers. For patients with acute systolic failure the
      inotropic agents continue to be useful in short term support but chronic
      administration with these agents should be avoided because of enhanced mortality
      observed in virtually all placebo controlled trials. Finally, long-term mortality
      rates remain high in patients with systolic dysfunction despite current therapy,
      thus offering an opportunity for the novel approaches currently under
      investigation to substantially impact on patient outcomes. (c)1999 by CHF, Inc.

PMID- 12189330
TI  - Effects of fosinopril on exercise tolerance, symptoms, and clinical outcomes in
      patients with decompensated heart failure.
AB  - The purpose of this prospective, multicenter, randomized, double blind, placebo
      controlled study was to determine the clinical effects of fosinopril in patients
      with decompensated or worsening heart failure (HF). Patients >/=18 years with New
      York Heart Association (NYHA) functional class II-IV HF who had been hospitalized
      or seen in the ER or outpatient clinic for treatment of worsening or
      decompensated HF were eligible. Patients had to be on diuretic therapy and have a
      left ventricular ejection fraction (LVEF) </=35% and a treadmill exercise
      tolerance test (ETT) duration of </=8 minutes. Randomized patients began 12 weeks
      of fosinopril 10 mg (or placebo) qAM and were titrated within 4 weeks to
      fosinopril 20 mg and then to 40 mg (or placebo) qAM (if seated, systolic blood
      pressure (SBP) >/=90 mm Hg). ETTs (modified Naughton protocol) were performed at
      weeks 1, 3, 6, and 12. A total of 206 patients (mean age 62 years) were
      randomized to fosinopril (n=102) or placebo (n=104). Most patients were NYHA
      functional class III (58%) or IV (30%) at presentation; 145 patients completed 12
      weeks of treatment (fosinopril, n=85; placebo, n=60). After adjustment for
      baseline imbalances and investigator effects, fosinopril-treated patients had a
      513 second mean exercise duration at endpoint vs. a 489 second duration in
      placebo-treated patients (p=0.353). When the analysis was adjusted for the impact
      of dropouts on ETT time, fosinopril-treated patients had a greater exercise
      duration than those treated with placebo (p=0.043). Fewer patients in the
      fosinopril group were discontinued from study medication (p=0.008) or
      hospitalized (p=0.005) for worsening HF. At endpoint, more patients improved
      their NYHA Functional Class and fewer had worsened with fosinopril vs. placebo
      (p=0.018); fosinopril-treated patients showed improvements in dyspnea (p=0.054),
      fatigue (p=0.052), edema (p=0.012), and paroxysmal nocturnal dyspnea (p=0.003)
      vs. the placebo group. Once-daily fosinopril had a favorable effect on dropout
      adjusted exercise tolerance, reduced the frequency of discontinuations or
      hospitalizations for worsening HF, improved HF signs and symptoms, and was safe
      and well tolerated. (c)1999 by CHF, Inc.

PMID- 12189331
TI  - Malaligned financial incentives of providers in the treatment of chronic
      diseases: the case of chronic heart failure.
AB  - Fee for activity based payment systems create a matrix of conflicting incentives.
      Hospitals, desiring to maximize revenues and minimize expenses, seek high patient
      volume with minimal direct variable expenses. The mix of patients, sought bias
      towards those whose disease related group (DRG), provide the largest contribution
      to hospitals fixed costs, are frequently characterized by the DRG with high
      reimbursements, coupled with both low length of stay and low utilization of
      expensive resources. Physicians, on the other hand, find hospital environments to
      be extraordinary practice sites. In the hospital, they can generate practice
      revenue without paying overhead for hospital resources. The incentives to rapidly
      discharge patients and reduce utilization of resources which are charged to the
      hospital's expense line are obscure. Hospital treatment of CHF frequently
      characterizes this conflict; hospitals are seeking rapid through put of CHF
      patients who neither require expensive hospital based resources nor demonstrate
      excessive length of stay. Physicians are not encumbered with immediate concerns
      about costs during the hospitalization, nor the length of hospitalization. The
      absence of absolute medical consensus on appropriateness of diagnostic and
      treatment strategies in this population has allowed significant variation on
      practice patterns to evolve, and consequently, variation on the contribution to
      hospital fiscal viability made by each physician. (c)1999 by CHF, Inc.

PMID- 12189333
TI  - Frontiers in congestive heart failure: Digoxin toxicity: an evaluation in current
      clinical practice.

PMID- 12189332
TI  - Difficult cases in heart failure: Bilateral renal artery fibrous dysplasia and
      heart failure.
AB  - The clinical characteristics as well as treatment of a patient with renal artery
      stenosis associated with uncontrolled hypertension and heart failure is
      described. Patients with similar findings should alert clinicians of this entity,
      since rapid diagnosis and treatment will assure a prompt relief not only of the
      increased blood pressure but also of the symptoms of heart failure. (c)1999 by
      CHF, Inc.

PMID- 12189334
TI  - Frontiers in congestive heart failure: High- versus low-dose ACE inhibition in
      chronic heart failure: a double-blind, placebo-controlled study of imidapril.

PMID- 12189335
TI  - Role of beta blockers in congestive heart failure.
AB  - Prolonged activation of the adrenergic nervous system has adverse consequences on
      the cardiovascular system in patients with congestive heart failure. Beta
      adrenergic receptor-blocker therapy modifies these deleterious effects. Beta
      blockers have been shown to improve myocardial function and survival when used in
      conjunction with conventional treatment with diuretics, angiotensin-converting
      enzyme inhibitors, and digoxin. Beta blocker therapy in mild-to-moderate heart
      failure should not be delayed because it causes some reversal of both
      neurohormonal compensatory mechanisms and the deleterious myocardial remodeling
      process. This paper reviews the beneficial effects of beta adrenergic receptor
      blocker therapy on the pathophysiology, symptoms, left ventricular function,
      morbidity, and mortality in patients with congestive heart failure. (c)2000 by
      CHF, Inc.

PMID- 12189336
TI  - Possible interaction between aspirin and ACE inhibitors: update on unresolved
      controversy.
AB  - The widespread use of aspirin and angiotensin converting enzyme (ACE) inhibitors
      in patients with coronary artery disease contributes significantly to the
      reduction in morbidity and mortality from this common health problem. These
      agents are widely and concomitantly used, and they share mechanisms that may
      interact in negative or positive pathways. Data derived from in vitro
      preparations, animal studies, human studies, and case-control studies are
      inconsistent. No study has established firm evidence regarding the safety or
      adverse effect of aspirin on patients who are on ACE inhibitors. The efficacy and
      safety of aspirin in combination with ACE inhibitors has been questioned and
      debated. If a negative interaction does exist, it will affect daily practice in
      treating patients with coronary artery disease and heart failure. This article
      reviews the available data regarding the safety of combined aspirin and ACE
      inhibitor treatment among patients with ischemic heart disease, to assess the
      possible interaction between the two drugs and to discuss the significance and
      implications of the data. (c)2000 by CHF, Inc.

PMID- 12189337
TI  - The AHF SCENE II Preceptorship Program: rationale and design of an educational
      program to optimize management of advanced heart failure.
AB  - Advanced heart failure requires specialized treatment to improve symptoms,
      increase survival, and reverse or slow disease progression. The Advanced Heart
      Failure Shared Clinical Experiences Network, or AHF SCENE, was founded in 1995 to
      provide small groups of health care professionals with better advanced heart
      failure management strategies by sharing clinical experiences from centers
      treating large numbers of patients. The original AHF SCENE program has since been
      modified to provide health care professionals with more information on current
      strategies for advanced heart failure management and to better serve the
      educational needs of professionals who care for these patients. AHF SCENE II
      promotes new methods, programs, procedures, and pharmacologic interventions and
      also describes strategies for tracking and improving clinical and economic
      outcomes in the management of advanced heart failure. AHF SCENE II supports the
      understanding that rapid, aggressive medical management is essential and is more
      effective in the context of a well designed program that spans the continuum of
      care. (c)2000 by CHF, Inc.

PMID- 12189338
TI  - Cardiac resynchronization for heart failure: present status.
AB  - Ventricular dysfunction is a hallmark of heart failure, and is often linked to
      ventricular dilatation and ventricular conduction delays. Recent studies have
      demonstrated that systolic function can be improved in patients with left bundle
      branch block by pre-exciting the site of late activation, usually the left
      ventricular free wall. Furthermore, it has been recently reported that this
      improvement is associated with a decrease in myocardial oxygen consumption. We
      hypothesize that the pre-excitation of the region covered by the blocked bundle
      acts as an "electrical bypass," resynchronizing the contraction of the septum and
      the left ventricular free wall. In addition, optimization of the electronic
      atrioventricular delay allows the simultaneous resynchronization of the
      atrioventricular contractions, and minimization of diastolic mitral
      regurgitation. Systolic mitral regurgitation may also be reduced by removing the
      geometric distortion introduced by the left bundle branch block. The recently
      reported positive outcome of the PATH-CHF I controlled trial reinforces that the
      positive acute and chronic results that have been reported up to now may
      translate into long-term clinical benefit for patients with heart failure and
      conduction defects. Larger studies are needed to confirm these initial results
      and to establish the impact of this new therapeutic modality on morbidity and
      mortality. (c)2000 by CHF, Inc.

PMID- 12189339
TI  - Pharmacotherapy in congestive heart failure: ACE inhibitors and anemia in
      congestive heart failure.
AB  - The use of angiotensin-converting enzyme inhibitors can be accompanied by a
      number of adverse events, including cough, angioedema, and hyperkalemia, as well
      as a peculiar form of functional renal insufficiency. Other, less obvious side
      effects accompany ACE inhibitor use, such as a reduction in red blood cell
      production. This feature of ACE inhibitor use may be employed to good effect, as
      in the management of post-transplant erythrocytosis. Alternatively, the
      suppressive effect of ACE inhibitors on red blood cell production may intensify
      the anemia of chronic renal failure and/or congestive heart failure. The
      untreated congestive heart failure patient typically has an increased red blood
      cell mass as a consequence of increased erythropoietin levels, with the latter
      governed by congestive heart failure-related renal hypoxia. This is not expressed
      as an increase in hemoglobin concentration because of the increase in plasma
      volume that marks advanced congestive heart failure. ACE inhibitor therapy can be
      expected to both reduce plasma volume and decrease red blood cell production. As
      a result, the hemoglobin concentration changes very little in the ACE inhibitor
      treated congestive heart failure patient and usually falls in the low normal
      range. Recently, erythropoietin has been employed to good effect in congestive
      heart failure patients with borderline anemia. (c)2000 by CHF, Inc.

PMID- 12189340
TI  - Difficult cases in heart failure: Ventricular resynchronization in refractory
      heart failure.
AB  - The use of a multisite transvenous pacemaker in a patient with refractory heart
      failure who experienced short-term symptomatic improvement is described. The
      improvement in heart failure symptoms was most likely related to
      resynchronization of atrioventricular and interventricular asynchrony. Large,
      multicenter, randomized trials of this technology are being performed to evaluate
      the importance of this therapeutic modality in the treatment of heart failure.
      (c)2000 by CHF, Inc.

PMID- 12189341
TI  - The National Heart Failure Project: a health care financing administration
      initiative to improve the care of Medicare beneficiaries with heart failure.
AB  - This is the second in a series describing Health Care Financing Administration
      (HCFA) initiatives to improve care for Medicare beneficiaries with heart failure.
      The first article outlined the history of HCFA quality-improvement projects and
      current initiatives to improve care in six priority areas: heart failure, acute
      myocardial infarction, stroke, pneumonia, diabetes, and breast cancer. This
      article details the objectives and design of the Medicare National Heart Failure
      Quality Improvement Project (NHF), which has as its goal the improvement of
      inpatient heart failure care. (c)2000 by CHF, Inc.

PMID- 12189342
TI  - Frontiers in congestive heart failure: Nonsurgical septal reduction therapy for
      hypertrophic obstructive cardiomyopathy: one-year follow-up.

PMID- 12189343
TI  - Frontiers in congestive heart failure: Rationale for the use of combination
      angiotensin-converting enzyme inhibitor/angiotensin II receptor blocker therapy
      in heart failure.

PMID- 12189344
TI  - Career aspirations.

PMID- 12189347
TI  - A survey of practicing nurses' perspectives on interpersonal violence screening
      and intervention.

PMID- 12189348
TI  - A decade of international activities by US nurse faculty: a descriptive analysis.
AB  - BACKGROUND: In this era of increasing international awareness, few studies have
      revealed the contributions of US nurse faculty abroad. PURPOSE: Our purpose was
      to assess the scholarly activities, defined as teaching, research, consultation,
      and service, of US nurse faculty abroad from 1985 to 1995. METHOD: As part of a
      larger study (J Nurs Scholarsh 2000;32:415-20), nurse scholars were asked to
      describe their international work from 1985 to 1995. Nursing faculty (N = 2254)
      from all (N = 62) nursing doctoral programs active in 1995 were mailed an
      investigator-developed questionnaire via their institution. FINDING: From 1010
      responses, 247 scholars described 805 visits to 109 countries. US nurse faculty
      assisted in the introduction and continuation of university-based nursing
      education worldwide. Research activities were either site-specific to the country
      or related to general issues. Geographic regions differed in the number of visits
      they received and the type of scholarly activity undertaken. CONCLUSIONS: US
      nurse faculty were involved in diverse and widespread international nursing
      activities.

PMID- 12189349
TI  - Educating students isn't the same as selling shoes.

PMID- 12189350
TI  - On the front lines of managed care: professional changes and communicative
      dilemmas of hospital nurses.
AB  - This article explores how the role of the hospital nurse has been transformed by
      managed care, with a concentration on changes relevant to communicative
      relationships and processes. Two brief case analyses are considered to examine
      how hospital nurses have felt the impact of being on the "front lines" of managed
      care. Findings illustrate the utility of a communication perspective in
      understanding changes in nursing at individual, organizational, and system
      levels.

PMID- 12189351
TI  - Resurfacing the care in nursing by telephone: lessons from ambulatory oncology.
AB  - The practice of providing telephone mediated advice and assistance is often
      described as "telephone triage" in relevant literature. The decision-making
      processes required for priority-setting and the provision of advice have been
      found to be complex and multifaceted. Conceptualization of this valuable patient
      care activity as a linear "triage" function serves to make invisible the nursing
      care provided. This article explores the current practice of providing telephone
      mediated advice and assistance in the following 2 distinct nursing care settings:
      emergency departments and ambulatory oncology centers. Examination of this
      activity in these 2 settings provides a forum to discuss and critique legally and
      fiscally driven prescriptive protocol use to inform decision-making. The
      effectiveness of experiential knowledge coupled with the strengths of nurse
      patient relationships suggests that a need exists to highlight the caring aspects
      of telephone mediated assistance.

PMID- 12189353
TI  - Position statement: integrating genetics competencies into baccalaureate and
      advanced nursing education.

PMID- 12189354
TI  - Refining the quality health outcomes model: differentiating between client trait
      and state characteristics.

PMID- 12189356
TI  - Reflections on being in the middle.

PMID- 12189357
TI  - Religious beliefs of patients and caregivers as a barrier to the pharmacologic
      control of cancer pain.

PMID- 12189358
TI  - Pharmacokinetics and electrocardiographic effects of a new controlled-release
      form of flecainide acetate: comparison with the standard form and influence of
      the CYP2D6 polymorphism.
AB  - OBJECTIVES: Our objectives were study the single- and repeated-dose
      pharmacokinetics and electrocardiographic effects (QRS duration) of a new
      controlled-release form of flecainide acetate compared with the immediate-release
      form and to examine the influence of CYP2D6 activity. METHODS: Twenty-four
      healthy subjects (6 men and 6 women at both dosages) received single and repeated
      doses of 100 or 200 mg immediate-release and controlled-release flecainide in a
      randomized crossover design. Electrocardiograms were recorded and flecainide
      plasma concentrations were measured before administration and up to 96 hours
      after administration. RESULTS: The controlled-release formulation had sustained
      release properties, with a significantly lower maximum concentration (C(max)) and
      delayed time to reach C(max). Compared with the immediate-release formulation,
      the relative bioavailability of the controlled-release formulation at steady
      state was 0.85 +/- 0.17 and 0.89 +/- 0.17 for the 100-mg/day and 200-mg/day
      doses, respectively. Trough flecainide plasma concentration at steady state was
      bioequivalent for both formulations. Maximum and minimum QRS increases were not
      significantly different for either the immediate-release or the controlled
      release form of flecainide after administration of both single and repeated
      doses. Mean QRS duration during a dosing interval at steady state correlated with
      mean plasma concentration for both forms (pooled data; P <.001). The 95%
      confidence interval for this regression was 26% narrower for the controlled
      release form than for the immediate-release form. Flecainide-induced QRS
      prolongation and pharmacokinetics were not significantly influenced by CYP2D6
      activity. CONCLUSIONS: Flecainide-induced QRS prolongation did not differ between
      the new controlled-release form and the immediate-release form. Flecainide plasma
      concentrations associated with the new controlled-release form predicted QRS
      prolongation with less variability compared with the immediate-release form. The
      CYP2D6 polymorphism did not appear to influence flecainide disposition kinetics
      or electrocardiographic effects at steady state.

PMID- 12189359
TI  - Low-dose ritonavir moderately enhances nelfinavir exposure.
AB  - BACKGROUND: The protease inhibitor ritonavir is increasingly administered at
      subtherapeutic doses in highly active antiretroviral treatment, to utilize its
      potential for drug interactions and to enhance the plasma concentrations of other
      concomitantly prescribed protease inhibitors. The addition of low doses of
      ritonavir to nelfinavir was investigated to describe the extent of
      pharmacokinetic interaction. METHODS: In this randomized, open-label, one
      sequence crossover study, nelfinavir 1250 mg twice a day was dosed for 17 days,
      followed by 14 days of nelfinavir 1250 mg twice a day plus low doses of ritonavir
      of either 100 mg or 200 mg orally. Twenty-four healthy volunteers were evaluated
      for pharmacokinetics of nelfinavir, its metabolite M8, and ritonavir. Plasma
      concentrations were measured up to 12 hours after morning and evening dosing,
      respectively, on days 14 and 31. RESULTS: Ritonavir increased the area under the
      plasma concentration-time curve (AUC) of nelfinavir by 20% (P =.024) and 39% (P
      =.001) after morning and evening administration, respectively. The AUC of
      nelfinavir metabolite M8 was increased by 74% and 86% after morning and evening
      dosing (P <.001 for both). CONCLUSION: During ritonavir combination therapy a
      clear although minor drug effect on nelfinavir pharmacokinetics was demonstrated
      but no dose effect was shown.

PMID- 12189361
TI  - Pharmacokinetics of valganciclovir and ganciclovir in renal impairment.
AB  - BACKGROUND: Valganciclovir is the oral prodrug of ganciclovir. The
      pharmacokinetics of valganciclovir in patients with renal impairment is not
      known. Furthermore, it is not known whether there are any pharmacokinetic
      differences between patients who are positive for human immunodeficiency virus
      (HIV) and cytomegalovirus (CMV) and healthy subjects. METHODS: A total of 44
      patients were included-18 with mild, medium, or severe renal impairment; 6 with
      end-stage renal disease who were on long-term hemodialysis; 8 HIV/CMV-positive
      patients with normal renal function; and 12 healthy subjects serving as controls.
      Valganciclovir and ganciclovir serum concentrations were measured after oral
      administration of 900 mg of valganciclovir. Pharmacokinetic parameters were
      estimated by means of noncompartmental and compartmental methods. RESULTS: After
      oral administration of the prodrug valganciclovir, ganciclovir bioavailability
      was 60% and ganciclovir concentrations were higher (maximum concentration
      [C(max)], 8.5 microg/mL versus 5.8 microg/mL) and appeared later (time to maximum
      concentration [T(max)], 4.3 versus 2.0 hours) in patients with severe renal
      impairment compared with healthy subjects. The elimination half-life (t(1/2)) of
      ganciclovir was longer in patients with renal failure (t(1/2) of 68.1 hours in
      patients with end-stage renal disease compared with 3.5 hours in healthy
      subjects). Ganciclovir clearance was correlated with creatinine clearance (r =
      0.975). Hemodialysis removed 50% of ganciclovir. We observed no differences in
      pharmacokinetics between HIV/CMV-positive patients and healthy subjects. A 2
      compartment model with zero-order input and first-order elimination proved to be
      the most appropriate model for ganciclovir after oral administration of
      valganciclovir. CONCLUSIONS: The dosage of valganciclovir has to be adjusted to
      the degree of renal impairment. Dosage adjustment is not necessary for HIV/CMV
      positive patients.

PMID- 12189360
TI  - Effect of coadministration of nelfinavir, indinavir, and saquinavir on the
      pharmacokinetics of amprenavir.
AB  - OBJECTIVE: Pharmacokinetic interactions are expected when human immunodeficiency
      virus (HIV) protease inhibitors are coadministered because many are both
      substrates for and inhibitors of CYP3A4. The goal of this model-based
      pharmacokinetic analysis was to describe the differences observed in amprenavir
      pharmacokinetics among treatment arms in the Adult AIDS Clinical Trial Group
      (AACTG) study protocol 398 and to propose mechanisms to account for them.
      METHODS: One hundred seventy-six HIV-positive subjects receiving 1200 mg
      amprenavir twice daily as part of AACTG protocol 398 were included in the
      pharmacokinetic study. All patients also received background medications
      efavirenz, adefovir dipivoxil, and abacavir and, depending on the study arm,
      placebo or one of the following protease inhibitors: nelfinavir, indinavir, or
      saquinavir. A population pharmacokinetic model was fitted to a total of 565
      amprenavir concentration measurements. The blood samples for concentration
      measurements were drawn at week 2 (12-hour pharmacokinetic study, approximately 7
      samples per study; 46 patients) and at week 24 (6-hour pharmacokinetic study,
      approximately 5 samples per study; 10 patients). In addition, samples were
      collected at 1 or more follow-up visits (population pharmacokinetic study, 1 to 3
      occasions per patient; 150 patients). RESULTS AND CONCLUSION: Amprenavir
      intrinsic clearance was significantly reduced relative to placebo by nelfinavir (
      41%) and indinavir (-54%) but not by saquinavir. The absolute magnitude of
      amprenavir intrinsic clearance suggests that CYP3A4 inhibition by nelfinavir and
      indinavir is balanced by enzymatic induction in the presence of the background
      drug(s), most likely efavirenz. Amprenavir intrinsic clearance apparently
      increases by more than 30% between weeks 2 and 24, possibly because of the time
      course of CYP3A4 induction.

PMID- 12189362
TI  - Pharmacokinetic modeling to predict morphine and morphine-6-glucuronide plasma
      concentrations in healthy young volunteers.
AB  - OBJECTIVE: This investigation focused on the development of a predictive model of
      morphine, including morphine-6-glucuronide (M6G) for healthy young volunteers
      after morphine administration. METHODS: Population compartmental pharmacokinetic
      modeling with NONMEM was applied to the plasma concentration-time data of
      morphine and M6G obtained from 8 healthy volunteers (4 men and 4 women; age
      range, 23 to 30 years) after intravenous bolus injection of 5.64 mg morphine base
      (7.5 mg morphine sulfate) and of 1 mg deuterium-labeled M6G. RESULTS: Two models
      were identified that described the plasma concentration versus time courses of
      morphine and M6G after administration of morphine. The model consisted of a
      standard 3-compartment model for morphine and a standard 2-compartment model for
      M6G, with input into and output from the central compartments. The formation of
      M6G from morphine was modeled as a fraction of morphine clearance of about 14%,
      which accounted for the formation of M6G, and a delay of the appearance of M6G in
      plasma modeled as a first-order process, with a mean metabolic transit time of
      17.2 minutes. An alternative model assigned the formation of M6G among the first
      peripheral compartment of morphine and the central compartment of M6G. Therefore
      the alternative 3-compartment model of morphine had the input into the central
      compartment and renal excretory elimination from the central compartment, but the
      metabolic clearance of morphine started from the first peripheral compartment.
      M6G was again modeled with a standard 2-compartment model. Both models predicted
      morphine and M6G plasma concentrations available from an independent study with
      acceptable accuracy and without bias. CONCLUSIONS: Two models are provided that
      can predict plasma concentrations of morphine and M6G with acceptable accuracy in
      healthy young volunteers.

PMID- 12189363
TI  - Severe 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) intoxication: insights into the
      measurement of hepatic cytochrome P450 1A2 induction.
AB  - OBJECTIVE: The correct in vivo quantification of aryl hydrocarbon receptor
      mediated induction of cytochrome P450 1A2 (CYP1A2) in humans is a long-standing
      question. We compared the performance of several modifications of the caffeine
      test for measurement of CYP1A2 activity in subjects with exceptionally high, low,
      or absent enzyme induction. METHODS: CYP1A2 activity was measured in 2 women
      highly exposed to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), in 1 man moderately
      exposed, and in 50 control subjects (30 nonsmokers and 20 heavy smokers). After
      the application of a test dose, caffeine demethylation was detected with the
      carbon 13 breath test, the total clearance, and several serum and urinary
      metabolite ratios. RESULTS: In the highly TCDD-exposed persons, results of the
      breath test (cumulative 15-minute dose), the total caffeine clearance, the serum
      metabolic ratio paraxanthine/caffeine (30 and 120 minutes after application), and
      the urinary metabolic ratio sum of 5-acetylamino-6-formylamino-3-methyluracil
      (AFMU), 1-methyluric acid (1U), and 1-methylxanthine (1X) over 1,7-dimethyluric
      acid (17U) showed a CYP1A2 activity 8 to 10 times higher than the mean of
      nonsmokers. In contrast, two caffeine urinary metabolic ratios with the parent
      substance in the denominator did not reflect the CYP1A2 enzyme induction. These
      ratios strongly depended on urine flow. For the breath test, only results
      evaluated for a short sampling period (eg, 15 minutes after application) revealed
      the high induction. Compared with nonsmokers, higher mean values (maximally 1.8
      times) were observed in smokers with all tests. CONCLUSION: After high TCDD
      exposure, hepatic CYP1A2 activity is inducible at least 10 times in humans.
      Moderate TCDD exposure (up to 1000 ppt in blood fat) does not cause a CYP1A2
      induction that can be measured to differentiate from background exposure
      individually. Therefore direct quantification of such toxins is more specific and
      sensitive.

PMID- 12189364
TI  - Peripheral prostanoid levels and nonsteroidal anti-inflammatory drug analgesia:
      replicate clinical trials in a tissue injury model.
AB  - BACKGROUND: Nonsteroidal anti-inflammatory drug (NSAID) analgesia is generally
      attributed to peripheral suppression of cyclooxygenase (COX) enzymes, leading to
      decreased products of the arachidonic acid cascade. This study evaluated the in
      vivo relationship between levels of prostanoids at the site of tissue injury and
      analgesia after systemic or local NSAID administration in a clinical model of
      tissue injury. METHODS: Subjects in two replicate clinical trials had one or two
      mandibular third molars removed and a microdialysis probe implanted at the
      surgical site for measurement of immunoreactive prostaglandin E(2) (PGE(2)) or
      immunoreactive thromboxane B(2) (TxB(2)) and pain measured concurrently. In the
      first study, ketorolac tromethamine (INN, ketorolac) was administered at pain
      onset in a 30-mg intramuscular dose, a 1-mg intramuscular dose, or a 1-mg
      submucosal dose at the extraction site in comparison with placebo. In the second
      study, subjects received either ketorolac tromethamine 30 mg by the intravenous
      route or placebo at pain onset. RESULTS: PGE(2) was detectable in the first
      postoperative sample, decreased over the next hour, and then increased
      significantly coincident with the onset of postoperative pain. Administration of
      30 mg ketorolac tromethamine produced parallel decreases in pain, PGE(2) levels,
      and TxB(2) levels at the surgical site. Administration of 1 mg ketorolac
      tromethamine intramuscularly or directly at the surgical site was analgesic but
      without measurable effects on PGE(2) levels. CONCLUSION: The temporal profile of
      PGE(2) and TxB(2) in the immediate postoperative period is consistent with
      constitutive COX-1 initially, followed by an increase in PGE(2) resulting from
      expression of COX-2. The temporal association between NSAID analgesia and
      decreased prostanoids at the site of injury is consistent with a dual COX-1/COX-2
      peripheral site of action. The analgesic effects of 1 mg ketorolac tromethamine
      without a reduction in PGE(2) at the site of injury suggests an additional
      central site for NSAID analgesia.

PMID- 12189365
TI  - Citalopram in pregnancy and lactation.
AB  - BACKGROUND: Although citalopram has gained wide acceptance in the treatment of
      depression and anxiety disorders, its use during pregnancy and lactation has been
      poorly characterized. The aim of this study was to examine the efficacy and
      safety of citalopram in relation to concentrations of citalopram and its
      metabolites during pregnancy and lactation. METHODS: Eleven mothers taking
      citalopram and their infants were enrolled in the study, and a control group of
      10 women who were not taking medication were prospectively matched for
      confounding obstetric characteristics at the time of delivery. Plasma and breast
      milk samples were collected from mother/infant pairs during pregnancy, at
      delivery, and for up to 2 months after delivery. Trough plasma and breast milk
      concentrations of citalopram, desmethylcitalopram, and didesmethylcitalopram were
      measured by HPLC. The pregnancy outcome was recorded, and the neurodevelopment of
      children was monitored for up to 1 year. RESULTS: Although the citalopram dose of
      20 mg to 40 mg once daily resulted in low maternal trough plasma concentrations
      (range, 46-214 nmol/L) and metabolites during pregnancy, only one subject
      required an increase of daily dose. The mean didesmethylcitalopram
      desmethylcitalopram metabolic ratio was significantly higher during pregnancy
      (54%, P <.001) than at 2 months after delivery, indicating induction of
      cytochrome P450 (CYP) 2D6 during pregnancy. At delivery, the trough plasma
      citalopram, desmethylcitalopram, and didesmethylcitalopram concentrations in the
      infants were 64%, 66%, and 68% of the maternal concentrations, respectively. The
      citalopram and metabolite concentrations in the milk were 2- to 3-fold higher
      compared with maternal plasma concentrations, but the infant citalopram and
      metabolite plasma concentrations were very low or undetectable. The delivery
      outcome and the neurodevelopment of all infants up to the age of 1 year were
      normal. CONCLUSION: Even though the sample size was limited, results from this
      prospective clinical trial suggest uncomplicated pregnancy outcome in mothers
      using citalopram during pregnancy and minimal exposure of the infants to
      citalopram during lactation. However, maternal therapeutic drug monitoring of
      citalopram should be recommended to minimize fetal exposure.

PMID- 12189366
TI  - Effect of sex and menstrual cycle phase on cytochrome P450 2C19 activity with
      omeprazole used as a biomarker.
AB  - BACKGROUND: Literature addressing the effect of sex on cytochrome P450 (CYP) 2C19
      activity is conflicting. The exogenous female sex steroid hormones used in oral
      contraceptives are believed to significantly inhibit CYP2C19 activity. However,
      the effect of variations in endogenous sex steroid concentrations throughout the
      menstrual cycle has not been investigated. OBJECTIVE: The objective of this study
      was to determine the effects of sex and menstrual cycle phase on CYP2C19 activity
      by using omeprazole. METHODS: White subjects with body weights between 45 and 66
      kg received a single oral dose of 30 mg omeprazole. Those with weights of 67 to
      90 kg received a dose of 40 mg. Twelve female subjects were phenotyped during the
      midfollicular and midluteal phases of the menstrual cycle for 3 complete cycles.
      Twelve male subjects were phenotyped every 14 days for 12 weeks. The 2-hour
      postdose plasma concentration ratio of omeprazole to 5'-hydroxyomeprazole was
      used as a measure of CYP2C19 activity. All subjects were genotyped for CYP2C19*2
      and *3 alleles. RESULTS: Twelve women and 8 men were extensive metabolizers (EMs)
      with a CYP2C19*1/*1 genotype, whereas 4 male subjects were heterozygous
      (CYP2C19*1/*2). Median metabolic ratios during the midfollicular and midluteal
      visits were 0.845 and 0.930, respectively (P =.7). Sex had no effect on CYP2C19
      activity in CYP2C19*1/*1 EMs (0.875 for men versus 1.070 for women, P =.140). The
      median metabolic ratios of all individuals with 2C19*1/*1 and *1/*2 genotypes
      were 0.94 and 3.75, respectively. CONCLUSION: There is no sex difference in
      CYP2C19 activity in healthy white CYP2C19*1/*1 EMs with the omeprazole ratios. A
      gene-dose effect was observed. In addition, variations in endogenous sex steroid
      concentrations throughout the menstrual cycle did not influence CYP2C19 activity.

PMID- 12189367
TI  - A population phenotyping study of three drug-metabolizing enzymes in Kyushu,
      Japan, with use of the caffeine test.
AB  - OBJECTIVE: We assessed in vivo activities of cytochrome P450 1A2 (CYP1A2), N
      acetyltransferase 2, and xanthine oxidase in Japanese residents of Kyushu, the
      southern island of Japan. METHODS: One hundred eighty-two healthy volunteers (108
      men and 74 women) received a 150-mg oral dose of caffeine before they went to
      sleep. The concentrations of caffeine, caffeine metabolites, and uric acid in
      their overnight urine samples were analyzed. The CYP2A6 genotypes were determined
      in 66 of the 182 volunteers to assess whether they affected a metabolic ratio for
      CYP1A2 activity index. RESULTS: The metabolic ratio for CYP1A2 was not
      polymorphic, but its mean ratio was greater in smokers than in nonsmokers (P
      <.05). Twenty subjects (11.0%) were found to be slow acetylators. Twenty subjects
      were determined to be putative poor metabolizers of xanthine oxidase, and the
      mean urinary uric acid concentration of those subjects was 53% lower than that of
      the other subjects (P <.0001). The mean ratio for CYP1A2 obtained from 3 subjects
      with the CYP2A6(*)4C/CYP2A6(*)4C genotype was greater than the mean ratio from
      subjects with other genotypes (P <.01) or that from subjects with a wild-type
      CYP2A6(*)1A allele (P <.05). CONCLUSIONS: Our results suggest that putative poor
      metabolizers of xanthine oxidase activities exist in a Japanese population and
      that a decreased 1,7-dimethyluric acid formation from caffeine in poor
      metabolizers of CYP2A6 appears to affect the metabolic ratio used for the
      assessment of CYP1A2 activity.

PMID- 12189368
TI  - Role of human MDR1 gene polymorphism in bioavailability and interaction of
      digoxin, a substrate of P-glycoprotein.
AB  - OBJECTIVE: Our objective was to quantitate the contribution of the genetic
      polymorphism of the human MDR1 gene to the bioavailability and interaction
      profiles of digoxin, a substrate of P-glycoprotein. METHODS: The pharmacokinetics
      of digoxin was studied in 15 healthy volunteers, who were divided into 3 groups
      (n = 5 each) on the basis of genotyping for the MDR1 gene, in a 4-dose study
      after single doses of digoxin alone (0.5 mg orally and intravenously) and
      coadministered with clarithromycin (400 mg orally for 8 days). The dose of
      digoxin was reduced during the clarithromycin phase (0.25 mg orally and
      intravenously). RESULTS: The bioavailability of digoxin in G/G2677C/C3435,
      G/T2677C/T3435, and T/T2677T/T3435 subjects were 67.6% +/- 4.3%, 80.9% +/- 8.9%,
      and 87.1% +/- 8.4%, respectively, and the difference between G/G2677C/C3435 and
      T/T2677T/T3435 subjects was statistically significant (P <.05). The MDR1 variants
      were also associated with differences in disposition kinetics of digoxin, with
      the renal clearance being almost 32% lower in T/T2677T/T3435 subjects (1.9 +/-
      0.1 mL/min per kilogram) than G/G2677C/C3435 subjects (2.8 +/- 0.3 mL/min per
      kilogram), and G/T2677C/T3435 subjects having an intermediate value (2.1 +/- 0.6
      mL/min per kilogram). Coadministration of clarithromycin did not consistently
      affect digoxin clearance or renal clearance. However, a significant increase in
      digoxin bioavailability was observed in G/G2677C/C3435 subjects (67.6% +/- 4.3%
      versus 85.4% +/- 6.1%; P <.05) but not in the other 2 genotype groups.
      CONCLUSION: The allelic variants in the human MDR1 gene are likely to be
      associated with altered absorption and/or disposition profiles of digoxin and P
      glycoprotein-mediated drug interaction

PMID- 12189369
TI  - Risk factors for antituberculous chemotherapy-induced hepatotoxicity in Japanese
      pediatric patients.
AB  - OBJECTIVE: Our objective was to clarify risk factors associated with the
      development of severe hepatotoxicity during antituberculosis chemotherapy in
      Japanese children. METHODS: In a retrospective analysis in a 350-bed referral
      children's hospital in a metropolitan area, the medical charts of all pediatric
      patients who received antituberculosis chemotherapy between January 1995 and
      November 1999 were surveyed. Univariate and multivariate analyses were performed
      to find any demographic parameters (ie, sex, age, height, and body weight),
      clinical characteristics (ie, nutritional or developmental status, co-infection
      with hepatitis viruses [B or C] or human immunodeficiency virus, presence of
      extrapulmonary tuberculosis, or medical history of liver disease), or individual
      antituberculosis agents used that would be associated with the likelihood of
      development of severe hepatotoxicity during antituberculous chemotherapy. Severe
      hepatotoxicity (defined as an elevation of ALT and AST levels that were greater
      than 5 times the respective reference values) was attributed to the chemotherapy
      when it developed in children with normal pretreatment values for these
      parameters and no other potential causes were identified. Those who had abnormal
      ALT or AST values before treatment were excluded from analysis. RESULTS: Among
      the 117 patients surveyed (58 males and 59 females; age range, 0 to 16 years), 18
      were excluded from the analysis because of abnormal baseline ALT and AST values.
      Severe hepatotoxicity developed in 8 of the 99 eligible children, and all 8 of
      those children were younger than 5 years old. The univariate analysis revealed
      that the children in whom hepatotoxicity developed were significantly (P <.05)
      younger, were predominantly male, had extrapulmonary tuberculosis, and were given
      pyrazinamide more often than those who had no hepatotoxicity. However, the
      multivariate logistic regression analysis revealed that only age and the
      administration of pyrazinamide would have a significant contribution (P <.05) to
      the development of severe hepatotoxicity, with odds ratios of 143 (95% confidence
      interval, 4.2 to 4934.9) and 0.60 (95% confidence interval, 0.39 to 0.90),
      respectively: the estimated probability of development of hepatotoxicity in a
      typical pediatric patient at 1, 5, and 10 years receiving pyrazinamide with
      rifampin (INN, rifampicin) and isoniazid would be 0.95, 0.72, and 0.16,
      respectively. CONCLUSIONS: This study indicated that intensive monitoring of
      hepatotoxicity should be performed for younger children (<5 years) receiving
      pyrazinamide for antituberculosis chemotherapy.

PMID- 12189383
TI  - Modulating T-cell immunity to tumours: new strategies for monitoring T-cell
      responses.

PMID- 12189384
TI  - Targeting death and decoy receptors of the tumour-necrosis factor superfamily.

PMID- 12189385
TI  - Gene therapy to protect haematopoietic cells from cytotoxic cancer drugs.

PMID- 12189386
TI  - Epithelial-mesenchymal transitions in tumour progression.

PMID- 12189387
TI  - Mechanisms of smoking-related lung and pancreatic adenocarcinoma development.

PMID- 12189388
TI  - Fortuitous convergences: the beginnings of JUN.

PMID- 12189389
TI  - Histone methyltransferases, diet nutrients and tumour suppressors.

PMID- 12189391
TI  - The New South Wales Health Survey Program: Overview and methods, 1996-2000.

PMID- 12189392
TI  - New South Wales Mothers and Babies 1999.

PMID- 12189393
TI  - New South Wales Older People's Health Survey 1999.

PMID- 12189394
TI  - New South Wales Mothers and Babies 1998.

PMID- 12189395
TI  - Program for Enhanced Population Health Infostructure (PEPHI)--a report of
      responses to the November 2000 discussion paper.

PMID- 12189396
TI  - Trends in the prescribing of stimulant medication for the treatment of attention
      deficit hyperactivity disorder in children and adolescents in New South Wales.

PMID- 12189397
TI  - New South Wales Mothers and Babies 2000.

PMID- 12189398
TI  - Successful cochlear implantation in a child after recovery from a head and neck
      malignancy: a case report.
AB  - We present the case of a successful pediatric cochlear implantation that was
      carried out following bilateral perilingual deafness caused by meningitis during
      the treatment of a childhood malignant tumor. A rhabdomyosarcoma localized in the
      frontobasal area was removed from the child at the age of 2 years. He then
      received 11 months of postoperative cytostatic treatment. A purulent meningitis
      developed at the end of the chemotherapy, resulting in a major-grade, bilateral
      sensorineural hearing loss (practically a perilingual deafness). After 6 tumor
      free years and a meticulous preoperative assessment, a Nucleus 24 M cochlear
      implant was successfully implanted in the child's left ear. Two years after the
      operation, the child shows excellent hearing results and moderate speech
      development.

PMID- 12189399
TI  - Expression of A, B, C and DR antigens in definite Meniere's disease in a Spanish
      population.
AB  - To analyze the associations of HLA class I and II antigens in patients with
      Meniere's disease (MD) in southern Spain, 54 patients with definite MD according
      to the diagnostic scale of the AAO-HNS were compared with 534 normal controls in
      a prospective multicenter study. We performed a serological typing for A, B, C
      and DR specificities of the major histocompatibility complex and allele-specific
      amplification for HLA-DRB1. No differences were found in the distribution of
      class I antigens or DR antigens in patients with definite MD when they were
      compared with the control group. Our results suggest that HLA antigens do not
      determine an increased susceptibility to develop MD.

PMID- 12189400
TI  - Clinical consequences of feedback on ear surgery: the continuous recording of
      adverse events and complications with regard to reducing the number of surgeons
      who perform otosclerosis surgery.
AB  - Electronically stored data may be used to generate feedback overviews. This paper
      describes a method for establishing a picture of ear surgery complications. In
      this prospective study, the working definition of adverse events and
      complications is "incidents that are not intrinsic to the surgical procedure and
      that have a potential or actual negative effect on surgical outcome or
      postoperative morbidity". A simple method is used to categorise otologic adverse
      events and complications. This scale varies from adverse events (grade A) to
      death (grade D). All adverse events and complications in ear surgery that met
      this definition were documented electronically as part of continuous follow-up
      between 1 July 1992 and 30 June 1999. In the first 3 years, 1,009 ear operations
      were performed, and in 51 (5%) of them, adverse events or complications were
      noted during or after surgery. There were 30 (3%) grade A (adverse events), 18
      (2%) grade B (minor complications), 3 (0.3%) grade C (major complications) and no
      grade D complications. Otosclerosis surgery was evaluated additionally, because
      halfway through a 7-year period, the number of surgeons was changed. Only three
      experienced, senior members of staff were involved, and inexperienced residents
      no longer were allowed to perform this kind of surgery. The reduction of surgeon
      numbers did indeed improve the outcome of the stapes surgery. Our results were
      comparable to the literature. This monitoring of outcome-results in relation to
      changes in care can be seen as a study of care quality. A review of this kind
      links daily clinical practice to the literature and induces an improvement in
      quality.

PMID- 12189401
TI  - The effect of benzalkonium chloride on rabbit nasal mucosa in vivo: an electron
      microscopy study.
AB  - In this study we investigated the histopathological changes of nasal mucosa after
      the use of topical benzalkonium-chloride solution. In the study, 28 male New
      Zealand white rabbits were used. The animals were divided into two groups. In the
      first group, 50 micro l of 0.001% benzalkonium-chloride solution was sprayed into
      the right nostril and 50 micro l of 0.9% saline into the left twice daily for 14
      days. In the second group, the same solutions were applied twice daily for 28
      days. All of the biopsies from each nasal cavity were processed for electron
      microscopy. In the nostrils treated with 0.001% benzalkonium chloride, there were
      areas with obvious squamous cell metaplasia. Some cells showed broken cristae of
      the mitochondria. Degenerative changes in the supportive and olfactory cells,
      deformation of nuclei and the increase of heterochromatin were observed. The
      present investigation has shown that the application of topical benzalkonium
      chloride does induce degenerative morphologic changes in the nasal mucosa in
      rabbits in vivo.

PMID- 12189402
TI  - Vertigo and cranial nerve palsy caused by different forms of spontaneous
      dissections of internal and vertebral arteries.
AB  - In this report we compare a subintimal hemorrhage of a dissected vertebral artery
      to a subadventitial hemorrhage of a dissected extracranial internal carotid
      artery. A subintimal hemorrhage compresses the lumen of the artery. Therefore,
      magnetic resonance imaging (MRI), angiography and ultrasound are screening
      methods. For the subadventitial hemorrhage, which does not really compress the
      lumen but forms an aneurysmal dilatation, MRI is the only method of choice. We
      describe a case in which vertigo, nausea and vomiting are the only symptoms of a
      subintimal vertebral artery dissection. In this case an infarction of the
      cerebellar region supplied by the superior cerebellar artery could be
      demonstrated. Our second case demonstrates a palsy of the 10th, 11th and 12th
      cranial nerves, which is a less frequent symptom of internal artery dissections.
      The palsy of these cranial nerves seems to be caused by compression of the nerves
      or their nutritional arteries close to the aneurysmal dilatation of the
      subadventitial dissected internal carotid artery. In both cases clinical symptoms
      were resolved after anticoagulation.

PMID- 12189403
TI  - Changes in pulmonary venous flow patterns in patients with ventricular septal
      defect.
AB  - We studied pulmonary venous (PV) flow patterns using Doppler echocardiography in
      26 patients with ventricular septal defect less than 3 years of age. Fifteen
      patients had moderate or severe symptoms, and the remaining 11 had no significant
      symptoms. Peak velocity of PV diastolic flow and flow velocity integral of PV
      diastolic flow in the symptomatic patients were significantly larger than those
      in either asymptomatic patients or the normal controls. The ratio of PV diastolic
      flow velocity to PV systolic flow velocity and the ratio of flow velocity
      integral of PV diastolic flow to that of PV systolic flow in the symptomatic
      patients were significantly larger than those in either asymptomatic patients or
      the normal controls. The ratio of PV diastolic flow velocity to PV systolic flow
      velocity as well as the ratio of flow velocity integral of PV diastolic flow to
      that of PV systolic flow correlated with V wave in left atrial or pulmonary
      capillary wedge pressure and indexes of left ventricular mass and left atrial
      volume. We conclude that the abnormal pulmonary venous flow patterns in
      ventricular septal defect might be associated with large left-to-right shunting
      and left atrial pressure V wave.

PMID- 12189404
TI  - Impaired cardiorespiratory response to brief sudden strenuous exercise in the
      postoperative tetralogy of fallot patients: a ten-second pedaling test.
AB  - No studies of cardiorespiratory response to brief, sudden, strenuous exercise in
      patients after tetralogy of Fallot (TOF) repair have been reported. We
      investigated the exercise capacity of TOF patients using a ten-second pedaling
      test designed to study cardiorespiratory responsiveness to brief, sudden,
      strenuous exercise. We assessed exercise capacity using a ten-second pedaling
      test (ten seconds maximal of voluntary cranking as fast as possible against an
      ergometer's inertial resistance), coupled with a conventional ramp-type
      progressive exercise test at a constant rate to the limit of tolerance, in eight
      male postoperative TOF patients and eight male control subjects. In the ten
      second pedaling test, there were no significant differences in the integrated
      areas of heart rate (HR) and oxygen uptake () responses between the TOF patients
      and controls, but there were significantly longer decreasing phase time constants
      of HR and responses in the TOF patients than in the controls. In the conventional
      exercise test, the endurance time, peak-HR, and peak- did not differ between the
      groups. The TOF group, with a normal exercise capacity assessed by a conventional
      exercise test, had an impaired cardiorespiratory response to brief, sudden,
      strenuous exercise assessed by a ten-second pedaling test.

PMID- 12189405
TI  - Value of the new Doppler-derived myocardial performance index for the evaluation
      of right and left ventricular function following repair of tetralogy of fallot.
AB  - The systolic and diastolic function in both ventricles may be altered even after
      successful corrective surgery of tetralogy of Fallot. The aim of this study was
      to assess the combined diastolic and systolic function of both ventricles using
      the Doppler-derived myocardial performance index (MPI) in patients with operated
      tetralogy of Fallot (TOF). We performed a prospective analysis of 51 patients
      following corrective surgery of TOF: 21 had a subannular patch, 20 had a
      homograft implantation at initial operation, and 10 were reoperated with
      secondary homograft implantation. Patients were examined with Doppler
      echocardiography, and the MPI, which incorporates ejection and isovolumetric
      relaxation and contraction times and is an index of global ventricular function,
      was calculated 10.2 +/- 8.0 (0.89-36) years after surgery. In 86.4% of the
      examined patients the right ventricular isovolumetric relaxation time was
      shortened compared to the normal published range or even did not exist (negative
      value) (p <0.01). The right ventricular MPI was paradoxically below the normal
      published range in 76.5% of the examined patients. The left ventricle global
      function was impaired in 23.5% of the examined patients, mainly due to altered
      systolic function with a prolonged left ventricular isovolumetric contraction
      time. The z score of the comparison between patients' left ventricular
      isovolumetric contraction time and the normal published values was 3.03. Patients
      with severe pulmonary regurgitation also had a prolongation of the isovolumetric
      relaxation time compared to patients with mild to moderate pulmonary
      regurgitation. The noncompliant right ventricle may shorten the right ventricular
      isovolumetric relaxation time, resulting in a paradoxically low right MPI. This
      may reduce the sensitivity of the index in recognizing patients with right
      ventricular dysfunction following corrective surgery of TOF. Additional diastolic
      impairment occurs in patients with right ventricular volume overload.

PMID- 12189406
TI  - Predictors of refractory tachycardia in infants with supraventricular
      tachycardia.
AB  - Reentrant supraventricular tachycardia (SVT) is the most common arrhythmia in
      infants. There are few predictors as to which patients will have recurrent or
      refractory SVT. We retrospectively reviewed records of all infants with SVT
      evaluated at The Hospital for Sick Children, Toronto, between January 1, 1995,
      and December 31, 1999. Patients with reentrant SVT documented in infancy and
      structurally normal hearts were included. Patients were placed in two groups: the
      "simple" group consisted of patients with SVT completely controlled by not more
      than one medication, and the "complex" group consisted of patients with recurrent
      episodes requiring at least one medication change for control. Forty-two cases
      were analyzed-23 in the simple group and 19 in the complex group. One patient in
      each group died. Age at presentation was 50.4 +/- 13.2 days for the simple group
      versus 10.2 +/- 2.5 days for the complex group (p <0.01). Complex patients were
      treated with a median of three medications and were more likely to have
      echocardiographically reduced ventricular function. The surface electrocardiogram
      RP interval during SVT was significantly longer in complex patients (p <0.001).
      There were no differences between the groups in gender, cycle length in SVT or
      sinus rhythm, the presence of pre-excitation, initial medication choice, or
      duration of therapy. Recurrent SVT in infancy is associated with younger age
      and/or ventricular dysfunction at presentation and also with slower
      ventriculoatrial conduction. The similar duration of therapy for simple and
      complex patients suggests that the early clinical course of SVT in infancy is not
      predictive of long-term outcome.

PMID- 12189407
TI  - Electrocardiographic depolarization and repolarization: long-term after Kawasaki
      disease.
AB  - To assess myocardial electric potentials late after Kawasaki disease (KD) we
      measured signal-averaged electrocardiography (SAECG) and QT dispersion
      parameters. Thirteen patients with persistent coronary aneurysm (group I), 12
      with late resolution of the aneurysm (>3 months) (group II), and 13 with early
      resolution (group III) were studied 7.9 +/- 3.9, 6.7 +/- 3.9, and 7.2 +/- 3.6
      years after the initial diagnosis (p = NS). In group I, myocardial infarction
      occurred in one patient during the acute illness, and coronary thrombosis in
      another; all except two patients had giant aneurysm (n = 8) and/or stenosis (n =
      7). At 40-Hz high-pass filter SAECG, terminal 40-msec root mean square amplitude
      (RMS40) was significantly lower in group I versus II and III (64.1 +/- 40.8
      microV, 79.9 +/- 47.2 microV, and 115 +/- 65.4 microV, respectively; p <0.05).
      Global QT dispersion was significantly greater in group I versus III (52 +/- 11
      msec and 37 +/- 11 msec, respectively; p <0.05), but not in comparison to group
      II (45 +/- 13 msec). The same trend was present for rate-corrected QT dispersion,
      without reaching statistical significance (84.0 +/- 34, 71.5 +/- 31, and 61.8 +/-
      21 respectively). Both depolarization and repolarization parameters are altered
      in patients with persistent coronary artery aneurysms long-term after KD. This
      may represent risk factors for developing ventricular arrhythmia in a growing
      population.

PMID- 12189408
TI  - Complete atrioventricular block following myocarditis in children.
AB  - Complete atrioventricular block (CAVB) can be either congenital or acquired in
      children. Acquired CAVB is occasionally seen in myocarditis patients. To
      determine the etiology, natural history, and outcome of children with acquired
      nonsurgical CAVB, we retrospectively reviewed nine children who had suffered CAVB
      caused by suspected infectious myocarditis. All of them had CAVB with a wide QRS
      escape ventricular rhythm on admission. Three of them had ventricular tachycardia
      in addition to CAVB. Seven of them had a preceding upper respiratory tract
      infection. All of them had congestive heart failure. Five of them had Stokes
      Adams seizures. Three etiologies were identified in four of the children. All
      patients received inotropic agents and emergency temporary pacing. In all except
      one case, the cardiac rhythm returned to sinus rhythm within 10 days. During a
      follow-up period of 9 to 96 months, all were asymptomatic and drug-free.
      Electrocardiograms showed that four patients were completely normal, there was
      complete RBBB in four and left anterior fascicular block in one patient. We
      conclude that although CAVB associated with myocarditis can be life-threatening,
      the long-term prognosis is good if patients are diagnosed early and proper
      management is employed.

PMID- 12189409
TI  - Expression of adenylyl cyclase V/VI mRNA and protein is upregulated in cyanotic
      infant human myocardium.
AB  - We have previously demonstrated that both basal and isoproterenol-stimulated
      activities of myocardial adenylyl cyclase were greater in cyanotic patients with
      tetralogy of Fallet (TOF) than those in acyanotic patients. However, it was not
      determined whether increased enzyme activity was related to a similar increase in
      adenylyl cyclase protein and mRNA expression. In the current study, we examined
      the mRNA and protein expression of cardiac adenylyl cyclase, types V and VI, in
      cyanotic and acyanotic patients with TOF. Ribonuclease protection assays and
      immunoblotting were performed on myocardial specimens obtained from cyanotic
      patients with TOF and acyanotic patients with TOF or ventricular septal defect.
      We demonstrated that in both cyanotic and acyanotic patients, there was more type
      V adenylyl cyclase mRNA than type VI. Types V and VI cardiac adenylyl cyclase
      mRNA were significantly increased in myocardium of the cyanotic group compared to
      the acyanotic group. Protein expression of both V and VI adenylyl cyclases was
      correspondingly upregulated in cyanotic patients compared to acyanotic patients.
      Our results indicate that gene and protein expression of cardiac adenylyl
      cyclases, types V and VI, is increased in the cyanotic myocardium. These results
      suggest that chronic hypoxemia may regulate the expression of adenylyl cyclase
      enzymes.

PMID- 12189410
TI  - Growth of an atrial septal defect: missing the window for transcatheter closure.
AB  - We describe a patient diagnosed with a small atrial septal defect (3-4 mm) that
      had grown to 24 mm in diameter over a six-year period. Timing of transcatheter
      intervention may be affected by growth of the atrial septal defect and this
      reports the first case of an atrial septal defect outgrowing the possibility of
      transcatheter closure.

PMID- 12189411
TI  - Perioperative course in two cases of tetralogy of fallot with portal venous
      atresia.
AB  - We report here two rare surgical cases of tetralogy of Fallot with portal venous
      atresia. Both patients, previously diagnosed with tetralogy of Fallot, developed
      portal hypertension and showed hematemesis and/or melena. One patient needed
      endoscopic sclerotherapy. Intracardiac repair was performed under cardiopulmonary
      bypass (CPB) with moderate hypothermia. After surgery, one of the patients
      developed cardiogenic shock due to cardiac tamponade with accumulated chyle in
      the pericardial sac in the ninth postoperative day, and showed deteriorated liver
      function, suggesting that liver might have been vulnerable because of the absence
      of portal blood.

PMID- 12189412
TI  - Idiopathic multifocal intracardiac and pulmonary thrombosis: successful treatment
      with rTPA.
AB  - A 21-month-old boy with respiratory symptoms for one month secondary to
      idiopathic multichamber intracardiac and pulmonary thrombosis is presented who
      was successfully treated with recombinant tissue plasminogen activator (rTPA).
      The etiology and risk factors of pediatric intracardiac thrombosis are discussed
      and the literature and all reported cases are reviewed. It is important to
      consider cardiopulmonary thrombosis as a differential diagnosis of respiratory
      distress in childhood.

PMID- 12189413
TI  - Biventricular pacing for successful weaning from extracorporal circulation in an
      infant with complex tetralogy of fallot.
AB  - Biventricular pacing therapy is an innovative therapy for improving cardiac
      output in adult patients with severe heart failure. However, this technique is
      not yet used in infants with congenital heart disease. We present a six month old
      infant with tetralogy of fallot and atresia of the left pulmonary artery in which
      biventricular stimulation led to improved left ventricular function and
      successful weaning from extracorporeal circulation.

PMID- 12189414
TI  - Methicillin-resistant Staphylococcus aureus endocarditis following repair of
      tetralogy of Fallot.
AB  - Infectious endocarditis following cardiac surgery, particularly that caused by
      methicillin-resistant Staphylococcus, aureus is a rare and highly lethal
      complication. We report a case of a 2-year-old girl who developed methicillin
      resistant S. aureus endocarditis and mediastinitis following the intracardiac
      repair of tetralogy of Fallot using Dacron patches. The patient enveloped severe
      bacteremia accompanied by disseminated intravascular coagulation and progressive
      enlargement of vegetation. Despite this condition, the patient was successfully
      treated by repair using double autogenous pericardial patches. Aggressive removal
      of foreign material and replacement with autogenous tissue resulted in a
      favorable outcome.

PMID- 12189415
TI  - Left-to-right shunt via persistent left superior vena cava and hypoplastic
      coronary sinus.

PMID- 12189416
TI  - Coronary artery aneurysms after kawasaki disease in a patient with a single
      coronary artery.

PMID- 12189417
TI  - Factors influencing methicillin resistance in staphylococci.
AB  - Methicillin resistance in staphylococci is due to an acquired penicillin-binding
      protein, PBP2' (PBP2a). This additional PBP, encoded by mecA, confers an
      intrinsic resistance to all beta-lactams and their derivatives. Resistance levels
      in methicillin-resistant Staphylococcus aureus (MRSA) depend on efficient PBP2'
      production and are modulated by chromosomal factors. Depending on the genetic
      background of the strain that acquired mecA, resistance levels range from
      phenotypically susceptible to highly resistant. Characteristic for most MRSA is
      the heterogeneous expression of resistance, which is due to the segregation of a
      more highly resistant subpopulation upon challenge with methicillin. Maximal
      expression of resistance by PBP2' requires the efficient and correct synthesis of
      the peptidoglycan precursor. Genes involved in cell-wall precursor formation and
      turnover, regulation, transport, and signal transduction may determine the level
      of resistance that is expressed. At this stage, however, there is no information
      available on the functionality or efficacy of such factors in clinical isolates
      in relation to methicillin resistance levels.

PMID- 12189418
TI  - Promoter analysis of the sodium-responsive V-ATPase (ntp) operon in Enterococcus
      hirae.
AB  - The Enterococcus hirae ntp operon encodes all subunits of the vacuolar-type
      ATPase (V-ATPase), which transports Na(+) or Li(+). This operon is expressed
      preferentially in response to Na(+), but not to Li(+). Deletion analysis of the
      ntp promoter region in plasmids indicated that the AT-tract between -198 and -132
      is required for Na(+)-specific transcriptional regulation. In addition, lithium
      tolerant (LTR) mutants were isolated in which functional V-ATPase levels were
      high even in Na(+)-depleted medium. Western blot and Northern blot experiments
      revealed an increase in basal Na(+)-independent transcription in one of the
      mutants (LTR1). The nucleotide sequences of the ntp promoter region of the LTR
      mutants showed mutational conversion of single base-pairs between positions -23
      and +1. Na(+)-independent expression of a reporter gene linked to the ntp
      promoter in plasmids was elevated by base substitutions at -23 to +1, and
      promoter activity induced by these base substitutions was lost by deletion of the
      region between -198 and -132. These results suggest that the AT-tract between 
      198 and -132 is indispensable for transcription of the ntp operon.

PMID- 12189419
TI  - Aerobic metabolism of phenylacetic acids in Azoarcus evansii.
AB  - The aerobic metabolism of phenylacetic acid (PA) and 4-hydroxyphenylacetic acid
      (4-OHPA) was investigated in the beta-proteobacterium Azoarcus evansii. Evidence
      for the existence of two independent catabolic pathways for PA and 4-OHPA is
      presented. 4-OHPA metabolism involves the formation of 2,5-dihydroxyphenylacetate
      (homogentisate) and maleylacetoacetate catalyzed by specifically induced 4-OHPA 1
      monooxygenase and homogentisate 1,2-dioxygenase. The metabolism of PA starts by
      its activation to phenylacetyl-CoA (PA-CoA) via an aerobically induced
      phenylacetate-coenzyme A ligase. Phenylalanine (Phe) aerobic metabolism in this
      bacterium proceeds also via PA and PA-CoA. Whole cells of A. evansii transformed
      [1-(14)C]PA to (14)C-phenylacetyl-CoA and subsequently to a number of unknown
      labeled products, which were also observed in PA-degrading bacteria from
      different phylogenetic groups, i.e. Escherichia coli, Rhodopseudomonas
      palustrisand Bacillus stearothermophilus. A chromosomal region from A. evansiiof
      11.5 kb containing a cluster of 11 phenylacetic acid catabolic ( paa) genes (
      paaYZGHIKABCDE) was sequenced and characterized. The derived gene products were
      similar to the characterized putative gene products involved in PA catabolism in
      E. coli and Pseudomonas putida and to other putative PA catabolic gene products
      of diverse bacteria. RT-PCR analysis of the paa genes of A. evansiigrowing
      aerobically with PA showed a probable organization of the paa genes in three
      operons. The similarity of the PA metabolic products pattern and of gene
      sequences suggests a common aerobic bacterial PA pathway.

PMID- 12189420
TI  - Genetic analysis of pigment biosynthesis in Xanthobacter autotrophicus Py2 using
      a new, highly efficient transposon mutagenesis system that is functional in a
      wide variety of bacteria.
AB  - A highly efficient method of transposon mutagenesis was developed for genetic
      analysis of Xanthobacter autotrophicus Py2. The method makes use of a transposon
      delivery vector that encodes a hyperactive Tn 5 transposase that is 1,000-fold
      more active than the wild-type transposase. In this construct, the transposase is
      expressed from the promoter of the tetA gene of plasmid RP4, which is functional
      in a wide variety of organisms. The transposon itself contains a kanamycin
      resistance gene as a selectable marker and the origin of replication from plasmid
      R6K to facilitate subsequent cloning of the resulting insertion site. To test the
      effectiveness of this method, mutants unable to produce the characteristic yellow
      pigment (zeaxanthin dirhamnoside) of X. autotrophicus Py2 were isolated and
      analyzed. Transposon insertions were obtained at high frequency: approximately 1
      x 10(-3) per recipient cell. Among these, pigment mutants were observed at a
      frequency of approximately 10(-3). Such mutants were found to have transposon
      insertions in genes homologous to known carotenoid biosynthetic genes previously
      characterized in other pigmented bacteria. Mutants were also isolated in
      Pseudomonas stutzeri and in an Alcaligenes faecalis, demonstrating the
      effectiveness of the method in diverse Proteobacteria. Preliminary results from
      other laboratories have confirmed the effectiveness of this method in additional
      phylogenetically diverse species.

PMID- 12189421
TI  - PsrR, a member of the AraC family of transcriptional regulators, is required for
      the synthesis of Wolinella succinogenes polysulfide reductase.
AB  - Wolinella succinogenes grows by polysulfide respiration with formate or hydrogen
      as electron donor. Polysulfide reduction is catalyzed by the membrane-bound
      polysulfide reductase complex encoded by the psrABC operon. An open reading
      frame, designated psrR, was found in close proximity upstream of the psr operon,
      but oriented in the opposite direction. The deduced amino acid sequence of PsrR
      is similar to those of transcriptional regulators of the AraC family and includes
      all typical features. Polysulfide reductase is not detectable in a Delta psrR
      deletion mutant of W. succinogenes. Mutant cells grown with fumarate as terminal
      electron acceptor did not catalyze polysulfide reduction with formate or
      hydrogen, in contrast to the wild-type strain. The phenotype of W. succinogenes
      wild-type cells was restored by genomic complementation of W. succinogenes Delta
      psrR. The results suggest that the gene product of psrR is involved in the
      regulation of polysulfide reductase synthesis.

PMID- 12189422
TI  - Characterization of four olive-mill-wastewater indigenous bacterial strains
      capable of aerobically degrading hydroxylated and methoxylated monocyclic
      aromatic compounds.
AB  - Seven aerobic bacterial strains capable of degrading several of the monocyclic
      aromatic compounds occurring in the phenolic fraction of olive-mill wastewaters
      (OMWs) were isolated from an Italian OMW. The results of the 16S rDNA restriction
      analysis evidenced that these strains are distributed among four different
      groups. One strain of each group was taxonomically characterized by sequencing
      the amplified 16S rDNA, and the four strains were assigned to the genera
      Comamonas (strain AV1A), Ralstonia (strain AV5BG), Pseudomonas (strain AV2A) and
      Sphingomonas (strain AV6C). The four strains, when checked for the ability to
      degrade nine monocyclic aromatic compounds abundant in OMWs, were found to
      significantly metabolize five to eight of them, both as resting cells and growing
      cells. Specific enzyme analyses of the same selected strains showed: (1) the
      occurrence of O-demethylating activities towards four methoxylated mono-aromatic
      acids in three of the four studied strains (strains AV1A, AV5BG and AV6C), (2)
      ring-cleavage activity towards protocatechuic acid in all of the strains, and (3)
      a ring-cleavage activity towards catechol in strain AV6C. The isolates described
      here exhibit a biodegradation potential towards monocyclic aromatic compounds of
      OMWs that is markedly broader and higher than that displayed by other aerobic
      bacteria described previously. These features make them excellent candidates for
      removing the low-molecular-weight phenolic compounds persisting in the effluent
      following anaerobic digestion of OMWs.

PMID- 12189423
TI  - Genetic and biochemical characterization of exopolysaccharide biosynthesis by
      Lactobacillus delbrueckii subsp. bulgaricus.
AB  - Lactobacillus delbrueckiisubsp. bulgaricus produces exopolysaccharides (EPSs),
      which play a role in the rheological properties of fermented food products. Lb.
      bulgaricus Lfi5 produces a high-molecular-weight EPS composed of galactose,
      glucose, and rhamnose in the molar ratio 5:1:1. An 18-kb DNA region containing 14
      genes, designated epsA to epsN, was isolated by genomic DNA library screening and
      inverted PCR. The predicted gene products are homologous to proteins involved in
      the biosynthesis of other bacterial polysaccharides and the genetic organization
      was found to be similar to that of other eps clusters from lactic acid bacteria.
      Transcriptional analysis revealed that the 14 eps genes are co-ordinately
      expressed and transcribed as a single mRNA of 15-16 kb. The transcription start
      site of the promoter was mapped upstream of the first gene, epsA. Genes encoding
      glycosyltranferases were further studied by heterologous expression and
      functional assays. We showed that the epsE gene product is a phospho
      glucosyltransferase initiating the biosynthesis of EPS. Heterologous expression
      of epsE in a Lactococcus lactis epsDmutant restored EPS production, demonstrating
      its role and importance in EPS biosynthesis. Functional assays of other
      glycosyltransferases allowed their sugar specificity to be elucidated and an
      overall biosynthetic pathway for EPS synthesis by Lb. bulgaricus to be proposed.

PMID- 12189424
TI  - Alkane-1,2-diol-based glycosides and fatty glycosides and wax esters in
      Roseiflexus castenholzii and hot spring microbial mats.
AB  - The lipid composition of Roseiflexus castenholzii, a thermophilic filamentous
      phototrophic bacterium related to uncultivated filamentous phototrophic bacteria
      that predominate in hot spring microbial mats, is reported. R. castenholzii lipid
      extracts were dominated by components characterized by alkane-1-ol-2-alkanoate
      moieties glycosidically bonded to a C(6) sugar. Similar fatty glycosides, with an
      additional fatty acid esterified, were detected by HPLC-MS. R. castenholzii also
      produces a suite of wax esters ranging from 37 to 40 carbon atoms in length. In
      lipid extracts from two nonsulfidic hot spring microbial mats, similar alkane-1,2
      diol-based lipids were detected in minor amounts. R. castenholzii lipids are
      compared to lipids of mats and other thermophilic mat isolates.

PMID- 12189425
TI  - Low-pressure urethra in women: what does it mean and what can it be used for?

PMID- 12189426
TI  - Urogynecologic ultrasound is a useful aid in the assessment of female stress
      urinary incontinence--a prospective study with TVT procedure.
AB  - The aims of the study were to study the suitability of certain urogynecologic
      ultrasound parameters, e.g. descent of the urethrovesical (UV) junction on
      Valsalva, posterior urethrovesical (PUV) angle both at rest and on Valsalva, and
      funneling of the vesical neck, in the pre- and postoperative assessment of stress
      urinary incontinence (SUI) and to evaluate the efficacy and safety of tension
      free vaginal tape (TVT) for the surgical treatment of SUI. Forty-six consecutive
      women (mean age 61 years) with symptoms of SUI underwent TVT placement. The
      patients were examined prior to and on average of 11 weeks after the operation
      with perineal ultrasound. An upright coughing test on standing was performed
      every time. Operative success rate was 94% in this series. Urogynecologic
      perineal ultrasound examination seemed strongly to support an anamnestic
      diagnosis of genuine SUI, and TVT proved to be a safe and effective ambulatory
      procedure for the surgical treatment of SUI.

PMID- 12189427
TI  - Abdominal versus vaginal approach for the management of genital prolapse and
      coexisting stress incontinence.
AB  - Patients who undergo surgery because of genital prolapse and coexisting stress
      incontinence can be treated by a combination of surgical procedures via a unified
      route. We performed a retrospective study among 47 patients to compare
      micturition, defecation and prolapse symptoms after surgery, as well as duration
      of hospital stay and complication rate between patients who underwent a unified
      vaginal or abdominal surgical correction. All patients were treated between
      January 1995 and December 1997 in the University Medical Center Utrecht or St
      Antonius Hospital Nieuwegein, The Netherlands. Abdominal surgery was associated
      with a higher prevalence of difficulty in bladder emptying (relative risk (RR)
      2.3 (95% CI 1.4-8.4)), fecal incontinence (RR 3.4, CI 1.1-10.7) and soiling (OR
      2.8, CI 1.2-6.2), as well as with a longer postoperative hospital stay (8.6 vs
      7.3 days) and a higher complication rate (25.0% vs. 11.4%) than vaginal surgery.
      These results suggest that a unified vaginal surgical correction of genital
      prolapse and coexisting stress incontinence appears to be preferable to a unified
      abdominal surgical correction.

PMID- 12189428
TI  - The safety of reusing injectable collagen: a multicenter microbiological study.
AB  - We have previously reported pilot data regarding the safety of saving partially
      used syringes of a glutaraldehyde cross-linked collagen for use in subsequent
      treatment sessions with the same individual. That single institution study
      involved 56 partially used syringes cultured for aerobic bacteria. Only one
      weakly positive culture was detected among these 56 samples, which prompted us to
      carry out this expanded study involving multiple centers and different injection
      techniques. Samples were collected from four centers. Following periurethral
      injection in an office setting, 166 partially used syringes of glutaraldehyde
      cross-linked collagen were refrigerated for between 1 and 104 weeks (average 58).
      Material from all 166 syringes was then cultured qualitatively and quantitatively
      for both aerobic and anaerobic organisms. Collagen from one syringe grew >100,000
      colonies of Escherichia coli. All other cultures were negative. In the pilot
      study, one culture of 56 syringes was weakly positive for coagulase-negative
      staphylococcus. When the results from both studies were considered together, only
      two of 222 partially used syringes (0.9%) were contaminated. The background risk
      of local infection associated with periurethral collagen injection is
      approximately 0.29%. Using the statistical equation 'number needed to harm', we
      found that a clinician would have to reuse 111 syringes at a saving of $34,965
      before he or she would cause a single local injection by so doing. Therefore, we
      feel that it may be cost-effective and safe to reinject material from a partially
      used syringe of glutaraldehyde cross-linked collagen during a subsequent
      treatment session on an individual.

PMID- 12189429
TI  - Controversies in female urethral anatomy and their significance for understanding
      urinary continence: observations and literature review.
AB  - To re-examine the anatomy of the female urethra and related structures, three
      female pelves serially sectioned in sagittal, coronal or transverse planes, and
      four sets of transverse histological slides of female urethras, were studied. The
      observations were assembled, rendered as illustrations, and correlated with
      published works to present an overall explanation of the gross and histological
      anatomy of the female pelvis and perineum as related to continence. The figures
      accompanying the text present the anatomy in a series of views in the three
      anatomical planes. The anatomical relationships of the paraurethral and
      paravaginal tissues are examined in relation to the conflicting nomenclature
      applied to these structures. The figures show the spatial relationships within
      the pelves and perineum that explain their effective function in urinary
      continence.

PMID- 12189430
TI  - Laparoscopic mesh and staple Burch colposuspension.
AB  - Our objective was to describe our experience with laparoscopic Burch
      colposuspension and to relate our results to traditional open Burch procedures
      for the treatment of genuine stress incontinence. Retrospective case series were
      compared to historical controls. Forty-six women found to have only genuine
      stress incontinence by history, examination and clinical urodynamics, underwent a
      mesh and staple laparoscopic Burch procedure. Follow-up ranged from 3 to 50
      months. Thirty-seven women were dry, 6 were improved and 3 showed no improvement.
      This compared to between 75% and 90% of women cured of stress incontinence by the
      traditional open Burch procedure. We concluded that the results of a mesh and
      staple laparoscopic Burch procedure in a carefully selected population of women
      with genuine stress incontinence appears comparable to that reported in the
      literature for an open Burch procedure.

PMID- 12189431
TI  - Relationship between stress urinary incontinence and pelvic organ prolapse.
AB  - We investigated the objective coexisting rate of stress urinary incontinence and
      pelvic organ prolapse, and also compared the treatment outcomes in patients who
      had both conditions, treated by a corrective operation on the basis of a precise
      preoperative evaluation. We reviewed 97 cases who underwent urodynamic studies
      and evaluation of the prolapse according to the Pelvic Organ Prolapse
      Quantification (POP-Q) system from among patients who were admitted for treatment
      of either stress urinary incontinence or pelvic organ prolapse. A Burch
      urethropexy, either alone or with a parvaginal repair, was done to correct the
      stress urinary incontinence, as well as additional operations to correct prolapse
      of stage II or more. The patients were evaluated postoperatively for the stress
      urinary incontinence and the degree of prolapse at every visit. Nineteen of 30
      (63.3%) patients who were admitted with stress urinary incontinence had a
      coexisting pelvic organ prolapse, most often of the anterior wall. In 42 of 67
      (62.7%) cases admitted with pelvic organ prolapse there was a coexisting stress
      urinary incontinence. A total of 61 patients who had both conditions were
      followed for 12 months postoperatively. The recurrence rate of stress urinary
      incontinence and prolapse (all of which were stage II) was 3.3% and 18.0%,
      respectively. It was noted that the greater the preoperative stage, the higher
      the recurrence rate (stage II 4.35%; stage III 25.0%; stage IV 33.6%). The
      coexisting rates of pelvic organ prolapse in patients having stress urinary
      incontinence, and stress urinary incontinence in patients having a pelvic organ
      prolapse, were both high. Therefore, when a preoperative evaluation that
      simultaneously considers both conditions and the correcting surgery is based on
      this evaluation, the recurrence rates of both conditions could be lowered.

PMID- 12189432
TI  - Interstitial cystitis coexisting with vulvar vestibulitis in a 4-year-old girl.
AB  - Interstitial cystitis (IC) is a disorder that is difficult to diagnose and is
      thought to be uncommon in children. We report the first case of IC coexisting
      with vulvar vestibulitis in a 4-year-old girl. She presented with urinary
      symptoms and pelvic and vulvar pain. Cystoscopic and histological investigation
      confirmed interstitial cystitis and vulvar vestibulitis. Gynecologists are often
      called upon to deal with symptoms referable to the genital tract. It is important
      to always include interstitial cystitis in the differential diagnosis of urinary
      symptoms associated with pelvic pain.

PMID- 12189433
TI  - Bowel perforation during insertion of tension-free vaginal tape (TVT).
AB  - A 56-year-old non-obese woman with a previous history of pelvic surgery underwent
      an uneventful TVT procedure for the treatment of genuine stress incontinence.
      Postoperatively she began to report an acute low abdominal pain and a secondary
      laparoscopy was performed. The view of the right iliac region showed the tape
      passing through a loop of the small intestine. The tape was cut in its
      intraperitoneal portion and the ileum freed and repaired. After the operation the
      patient recovered well and was discharged on the fifth day after laparoscopy.
      Despite the section of the tape, 1 year later the patient is objectively cured by
      the procedure.

PMID- 12189434
TI  - Cystoscopic confirmation of inadvertent ureteral catheterization during
      cystometry.
AB  - A patient in whom the right ureter was inadvertently catheterized at the time of
      cystometry is described. Upon filling, the patient immediately developed severe
      colicky right flank pain and the vesical pressure of 150 cmH(2)O triggered the
      pump's automatic shut-off mechanism. Cystoscopy was performed and confirmed the
      inadvertent placement of the microtip catheter in the right ureteral orifice.
      After the catheter was repositioned, symptoms resolved and the remainder of the
      examination was performed routinely, with normal vesical and urethral pressures.

PMID- 12189435
TI  - Urinary retention and intravesical hemorrhage following urethral collagen
      injections in women using warfarin.
AB  - Two women on warfarin anticoagulation experienced urinary retention following
      urethral collagen bulk injections. Both women developed implant site hematomas,
      with urinary retention and intravesical hemorrhage. One woman was
      supratherapeutic and the other was therapeutic on warfarin therapy. Both women
      required transfusion and prolonged catheterization.

PMID- 12189436
TI  - Transurethral resection versus open surgery for leiomyoma of urinary bladder--a
      report of 2 cases.
AB  - The authors describe two patients with leiomyoma of the bladder who presented
      with bladder outlet obstruction. The results of magnetic resonance imaging are
      presented and their management discussed. Complete resection was curative in both
      patients, by enucleation in the first case and by transurethral resection in the
      second.

PMID- 12189437
TI  - Quantitation of basal endogenous glucose production in Type II diabetes:
      importance of the volume of distribution.
AB  - The rate of endogenous glucose production (EGP) is important in understanding the
      pathophysiology of Type II (non-insulin-dependent) diabetes mellitus, the
      aetiology of its complications, and the identification of potential therapeutic
      targets. A great deal of effort has therefore been expended in its evaluation.
      Most measurements in humans have been made using tracers, or labelled analogues
      of glucose. Experimental strategies have included the injection and the infusion
      of such tracers which were often primed to achieve constant concentrations of the
      label more quickly. Primers have either been fixed or adjusted to the ambient
      glycaemia in each diabetic subject. Analyses were carried out using steady-state
      or non-steady-state calculations, the latter based on a one-compartment model or
      higher order systems. The principal finding of this review is that all approaches
      yield the same EGP when an appropriate model of the system is used. Under basal
      conditions, a single compartment model is sufficient to evaluate EGP, but the
      estimation of the volume of distribution, V, from individual data is critical in
      obtaining consistent results. Other sources of variation arose from the length of
      the fasting period and the patient population being studied. Overall, in Type II
      diabetes, EGP is frequently high in the morning and decreases gradually to rates
      comparable to healthy control subjects. This can be a very delayed response to a
      preceding meal, but more likely corresponds to an accentuated circadian rhythm in
      glucose production. Metabolic clearance of glucose, on the other hand, is
      decreased in diabetes, and remains so during the course of the day.

PMID- 12189438
TI  - Charcot neuroarthropathy in diabetes mellitus.
AB  - Charcot neuroarthropathy has been recognised for over 130 years and yet it
      remains a major cause of morbidity for patients with diabetes mellitus and a
      continuing challenge for physicians. It is rare but it seems to be increasing in
      prevalence and this provides hope that with larger studies it will soon be
      possible to clarify the natural history and optimal treatment regimens. The
      underlying cause is thought to be trauma in a neuropathic foot that leads to a
      complex series of pathological processes culminating in bone and joint
      destruction and subsequent deformity. The acute reaction is often misdiagnosed
      and many patients present late with established deformity. Even when the
      diagnosis is considered at an early stage there are no definitive criteria or
      tests to confirm charcot neuroarthropathy and a high index of suspicion is
      necessary in any diabetic patient with a swollen warm foot in the presence of
      somatic or autonomic neuropathy. Treatment has traditionally involved the use of
      various methods to avoid weight bearing but recent work has begun to suggest that
      bisphosphonates might be able to arrest the acute process. In the long term,
      treatment involves a multidisciplinary approach aimed at providing appropriate
      footwear to reduce plantar pressures and avoid foot ulceration; in some
      circumstances this involves surgical correction of deformities before adequate
      footwear can be supplied. Further studies of the emerging treatments for Charcot
      neuroarthropathy are needed to provide long-term outcome data on morbidity and
      deformity.

PMID- 12189439
TI  - The association between components of adult height and Type II diabetes and
      insulin resistance: British Women's Heart and Health Study.
AB  - AIMS/HYPOTHESIS: The aim of this study was to investigate the associations
      between components of adult height (leg length, trunk length, ratio of leg to
      trunk length) and Type II (non-insulin-dependent) diabetes mellitus and insulin
      resistance. METHODS: A cross sectional study was carried out on 4286 women of age
      60 to 79 years from 23 towns across England, Scotland and Wales. RESULTS: Total
      height was weakly and inversely associated with diabetes but this masked
      differences in the association with leg and trunk length. Leg length was
      inversely associated with Type II diabetes [age adjusted odds ratio (95% CI) for
      diabetes for each standard deviation (4.3 cm) increase in leg length: 0.81 (0.73,
      0.90)] whereas trunk length was not associated with diabetes [age adjusted odds
      ratio (95% CI) for diabetes for each standard deviation (3.6 cm) increase in
      trunk length: 1.05 (0.94, 1.18)]. Adjustment for potential confounding factors
      attenuated but did not remove the inverse association between leg length and the
      prevalence of diabetes: fully adjusted odds ratio (95% CI) per standard deviation
      increase in leg length was 0.87 (0.77, 0.98) and that per standard deviation
      increase in the ratio of leg to trunk length was 0.88 (0.78, 0.99). In non
      diabetic women leg length was inversely associated with insulin resistance,
      whereas trunk length was positively associated with insulin resistance.
      CONCLUSION/INTERPRETATION: Leg length is an indicator of early childhood
      environmental circumstances, in particular of infant nutrition. These results
      suggest that poor infant nutrition is an important causal factor in the
      development of Type II diabetes and insulin resistance in later life.

PMID- 12189440
TI  - Serum concentrations of the interferon-gamma-inducible chemokine IP-10/CXCL10 are
      augmented in both newly diagnosed Type I diabetes mellitus patients and subjects
      at risk of developing the disease.
AB  - AIMS/HYPOTHESIS: Chemokines are chemotactic cytokines controlling the recruitment
      of leukocytes from the blood by regulating integrin adhesiveness. It has been
      shown that the migration of CD4+Th1 and CD4+Th2 cells is governed by specific
      chemokines. Increasing evidence suggests that the CD4+Th1 cheomoattractant
      chemokine CXCL10, also termed Interferon (IFN)-gamma -inducible protein (IP)-10
      is pathogenetically involved in several immunoinflammatory and autoimmune
      diseases. METHODS: IFN-gamma and IP-10 were quantified by solid-phase ELISA in
      sera of patients with either newly diagnosed or long-term Type I (insulin
      dependent) diabetes mellitus, and in sera of their healthy first degree
      relatives. The latter were subdivided into "low" and "high" risk prediabetic
      subjects depending on whether they were negative or positive for the anti-beta
      cell autoantibodies ICA and GAD. RESULTS: Compared with healthy control subjects
      (18%, 9/50), those with a low risk of disease (21%, 5/24) and the group of
      patients with long-term Type I diabetes (24%, 12/50), IP-10 was found more
      frequently and at increased concentrations in both newly diagnosed Type I
      diabetic patients (84%, 42/50) and in those with a high risk of disease (73%,
      16/22); in the latter, the IP-10 concentrations correlated with those of IFN
      gamma. CONCLUSION/INTERPRETATION: Circulating IP-10 concentrations is increased
      in patients with Type I diabetes, but only during the early and subclinical stage
      of the disease.

PMID- 12189441
TI  - Defective amplification of the late phase insulin response to glucose by GIP in
      obese Type II diabetic patients.
AB  - AIMS/HYPOTHESIS: Glucagon-like-peptide-1 (GLP-1) is strongly insulinotropic in
      patients with Type II (non-insulin-dependent) diabetes mellitus, whereas glucose
      dependent insulinotropic polypeptide (GIP) is less effective. Our investigation
      evaluated "early" (protocol 1) - and "late phase" (protocol 2) insulin and C
      peptide responses to GLP-1 and GIP stimulation in patients with Type II diabetes.
      METHODS: Protocol 1: eight Type II diabetic patients and eight matched healthy
      subjects received i.v. bolus injections of GLP-1(2.5 nmol) or GIP(7.5 nmol)
      concomitant with an increase of plasma glucose to 15 mmol/l. Protocol 2: eight
      Type II diabetic patients underwent a hyperglycaemic clamp (15 mmol/l) with
      infusion (per kg body weight/min) of either: 1 pmol GLP-1 (7-36) amide (n=8), 4
      pmol GIP (n=8), 16 pmol GIP (n=4) or no incretin hormone (n=5). For comparison,
      six matched healthy subjects were examined. RESULTS: Protocol 1: Type II diabetic
      patients were characterised by a decreased "early phase" response to both
      stimuli, but their relative response to GIP versus GLP-1 stimulation was exactly
      the same as in healthy subjects [insulin (C-peptide): patients 59+/-9% (74+/-6%)
      and healthy subjects 62+/-5% (71+/-9%)]. Protocol 2, "Early phase" (0-20 min)
      insulin response to glucose was delayed and reduced in the patients, but enhanced
      slightly and similarly by GIP and GLP-1. GLP-1 augmented the "late phase" (20-120
      min) insulin secretion to levels similar to those observed in healthy subjects.
      In contrast, the "late phase" responses to both doses of GIP were not different
      from those obtained with glucose alone. Accordingly, glucose infusion rates
      required to maintain the hyperglycaemic clamp in the "late phase" period (20-120
      min) were similar with glucose alone and glucose plus GIP, whereas a doubling of
      the infusion rate was required during GLP-1 stimulation.
      CONCLUSION/INTERPRETATION: Lack of GIP amplification of the late phase insulin
      response to glucose, which contrasts markedly to the normalising effect of GLP-1,
      could be a key defect in insulin secretion in Type II diabetic patients.

PMID- 12189442
TI  - L-arginine infusion decreases plasma total homocysteine concentrations through
      increased nitric oxide production and decreased oxidative status in Type II
      diabetic patients.
AB  - AIMS/HYPOTHESIS: Hyperhomocysteinaemia increases cardiovascular risk in Type II
      (non-insulin-dependent) diabetes mellitus by augmenting oxidative stress and
      reducing nitric oxide availability. In vitro, nitric oxide decreases homocysteine
      by its conversion to the vasodilative and antioxidant compound S
      nitrosohomocysteine. We investigated whether or not changes in nitric oxide
      availability decrease homocysteine concentrations in vivo. METHODS: The study
      group consisted of 20 normotensive, normolipidaemic, non-atherosclerotic Type II
      diabetic patients in good metabolic control (16 men, 51.2+/-1.4 years) and 15
      healthy subjects (12 men, 48.1+/-1.5 years). Circulating concentrations of
      homocysteine, nitrite+nitrate and sulphydryl groups, a marker of oxidative
      stress, were assessed at baseline and then 5', 10', 30' and 60' after the
      intravenous infusion of either L-arginine (3 g in 10 ml saline), the nitric oxide
      precursor, or vehicle according to a double-blind cross-over randomized protocol.
      RESULTS: At baseline diabetic patients showed lower plasma sulphydryl group
      concentrations (491.8+/-16.9 vs 551.3+/-21.0 micro mol/l, p<0.04) and
      nitrite+nitrate (21.4+/-0.8 vs 29.5+/-0.9 micro mol/l, p<0.0001) and higher total
      homocysteine concentrations (11.1+/-0.5 vs 8.3+/-0.6 micro mol/l, p<0.002) than
      the control subjects. After L-arginine infusion, blood pressure levels and total
      homocysteine concentrations ( p< or =0.05) decreased (peak at 5' and 30',
      respectively) whereas nitric oxide and sulphydryl group concentrations ( p< or
      =0.003) increased (peak at 10' and 30', respectively) in the patients and control
      subjects. CONCLUSION/INTERPRETATION: Acute L-arginine infusion in both Type II
      diabetic patients and healthy subjects decreases plasma total homocysteine
      concentrations, counteract oxidative stress and increases the availability of
      nitric oxide.

PMID- 12189443
TI  - Insulin signal transduction and glucose transport in human adipocytes: effects of
      obesity and low calorie diet.
AB  - AIM/HYPOTHESIS: We examined insulin signal transduction at the level of insulin
      receptor substrates (IRS) 1 and 2, phosphatidylinositol (PI) 3-kinase and glucose
      transport in isolated subcutaneous adipocytes from obese and lean women. METHODS:
      Glucose transport and insulin signalling were investigated in isolated adipocytes
      from six obese women (BMI 36-43 kg/m(2)) (before and after 11 days of very low
      calorie diet) and from six lean women (BMI 22-26 kg/m(2)). RESULTS: Insulin
      sensitivity of glucose transport was reduced in adipocytes from obese women
      (p<0.05), with further reductions in basal and maximal insulin-stimulated glucose
      transport after a very low calorie diet (p<0.05). In obese women, IRS-1
      associated PI 3-kinase activity was markedly impaired (p<0.05), whereas, IRS-2
      associated PI 3-kinase activity was normal. IRS-1 associated PI 3-kinase activity
      remained blunted after a very low calorie diet, whereas IRS-2 associated PI 3
      kinase activity was increased. GLUT4 protein was reduced by 37% in obese versus
      lean subjects (p<0.05), and decreased further after a very low calorie diet (from
      19+/-4 to 14+/-4 arbitrary units; p<0.05). CONCLUSION/INTERPRETATION: IRS-1
      signalling to PI 3-kinase is a site of insulin resistance in adipocytes from
      obese women, whereas insulin action on IRS-2 is normal. Thus, IRS-1 and IRS-2
      undergo differential regulation in adipocytes from obese insulin resistant
      subjects. Finally, a very low calorie diet is associated with a further
      impairment in glucose transport in adipose tissue. The defect in glucose
      transport after a very low calorie diet occurs independent of further defects in
      insulin signalling at the level of the PI 3-kinase.

PMID- 12189444
TI  - Liver glucokinase gene expression is controlled by the onecut transcription
      factor hepatocyte nuclear factor-6.
AB  - AIMS/HYPOTHESIS: Glucokinase plays a key role in glucose homeostasis and the
      expression of its gene is differentially regulated in pancreatic beta cells and
      in the liver through distinct promoters. The factors that determine the tissue
      specific expression of the glucokinase gene are not known. Putative binding sites
      for hepatocyte nuclear factor (HNF)-6, the prototype of the ONECUT family of
      transcription factors, are present in the hepatic promoter of the glucokinase
      gene and hnf6 knockout mice are diabetic [corrected]. We hypothesized that HNF-6
      controls the activity of the hepatic glucokinase promoter. METHODS: We tested the
      binding of recombinant HNF-6 to DNA sequences from the mouse hepatic glucokinase
      promoter in vitro and the effect of HNF-6 on promoter activity in transfected
      cells. We investigated in vivo the role of HNF-6 in mice by examining the effect
      of inactivating the hnf6 gene on glucokinase gene-specific deoxyribonuclease I
      hypersensitive sites in liver chromatin and on liver glucokinase mRNA
      concentration. RESULTS: HNF-6 bound to the hepatic promoter of the glucokinase
      gene and stimulated its activity. Inactivation of the hnf6 gene did not modify
      the pattern of deoxyribonuclease I hypersensitive sites but was associated with a
      decrease of liver glucokinase mRNA to half the control value.
      CONCLUSIONS/INTERPRETATION: Although HNF-6 is not required to open chromatin of
      the hepatic promoter of the glucokinase gene, it stimulates transcription of the
      glucokinase gene in the liver. This could partly explain the diabetes observed in
      hnf6 knockout mice.

PMID- 12189445
TI  - Expression profile of MODY3/HNF-1alpha protein in the developing mouse pancreas.
AB  - AIMS/HYPOTHESIS: One subtype of MODY (MODY3) results from the heterozygous
      mutation of a hepatocyte nuclear factor (HNF)-1alpha. The pattern of HNF-1alpha
      expression in the normal pancreas has not been determined. This study aimed to
      clarify the profile of HNF-1alpha protein expression in the developing mouse
      pancreas. METHODS: Double immunofluorescence staining was carried out for HNF
      1alpha and pancreatic hormones or transcription factors (PDX-1, Pax6, Isl1, and
      Nkx2.2). The expression of these transcription factors was also studied in the
      beta cells of HNF-1 alpha mutant mice. RESULTS: HNF-1alpha was expressed by both
      endocrine and exocrine cells of the pancreas. Double immunofluorescence staining
      showed that HNF-1alpha was expressed in the nuclei of alpha cells, beta cells,
      delta cells, and pancreatic polypeptide (PP) cells. HNF-1alpha was first detected
      in most pancreatic epithelial cells on embryonic day 10.5 (E10.5), and hormone
      positive endocrine cells and amylase-positive cells expressed HNF-1alpha on
      E15.5. Most of the Pax6-, Isl1-, or PDX-1-positive cells showed co-expression of
      HNF-1alpha. However, HNF-1alpha immunoreactivity was not observed in 36.0% of
      Nkx2.2-positive cells. Expression of Nkx2.2, Isl1 and Pax6 seemed to be normal in
      the beta cells of transgenic mice with dominant negative overexpression of HNF
      1alpha. Expression of PDX-1 did not change in the beta cells of pre-diabetic HNF
      1 alpha (-/-) mice, but expression was markedly decreased in the diabetic stage.
      CONCLUSION/INTERPRETATION: HNF-1alpha is expressed by both endocrine cells and
      exocrine cells of the pancreas from the foetal stage along with other
      transcription factors, so HNF-1alpha might play a role during development.

PMID- 12189446
TI  - Disorganization of cytoplasmic Ca(2+) oscillations and pulsatile insulin
      secretion in islets from ob/ obmice.
AB  - AIMS/HYPOTHESIS: In normal mouse islets, glucose induces synchronous cytoplasmic
      [Ca(2+)](i) oscillations in beta cells and pulses of insulin secretion. We
      investigated whether this fine regulation of islet function is preserved in
      hyperglycaemic and hyperinsulinaemic ob/ obmice. METHODS: Intact islets from ob/
      ob mice and their lean littermates were used after overnight culture for
      measurement of [Ca(2+)](i) and insulin secretion. RESULTS: We observed three
      types of [Ca(2+)](i) responses during stimulation by 9 to 12 mmol/l of glucose:
      sustained increase, rapid oscillations and slow (or mixed) oscillations. They
      occurred in 8, 18 and 74% of lean islets and 9, 0 and 91% of ob/ ob islets,
      respectively. Subtle desynchronisation of [Ca(2+)](i) oscillations between
      regions occurred in 11% of lean islets. In ob/ ob islets, desynchronisation was
      frequent (66-82% depending on conditions) and prominent: oscillations were out of
      phase in different regions because of distinct periods and shapes. Only small ob/
      ob islets were well synchronised, but sizes of synchronised lean and
      desynchronised ob/ ob islets were markedly overlapped. The occurrence of
      desynchronisation in clusters of 5 to 50 islet cells from ob/ obmice and not from
      lean mice further indicates that islet hypertrophy is not the only causal factor.
      In both types of islets, synchronous [Ca(2+)](i) oscillations were accompanied by
      oscillations of insulin secretion. In poorly synchronised ob/ ob islets,
      secretion was irregular but followed the pattern of the global [Ca(2+)](i)
      changes. CONCLUSIONS/INTERPRETATION: The regularity of glucose-induced
      [Ca(2+)](i) oscillations is disrupted in islets from ob/ ob mice and this
      desynchronisation perturbs the pulsatility of insulin secretion. A similar
      mechanism could contribute to the irregularity of insulin oscillations in Type II
      (non-insulin-dependent) diabetes mellitus.

PMID- 12189447
TI  - The effect of polyneuropathy on foot microcirculation in Type II diabetes.
AB  - AIMS/HYPOTHESIS: The aim of this study was to investigate the influence of
      peripheral polyneuropathy (PNP) on skin microcirculation and foot swelling rate
      in the feet of patients with Type II (non-insulin-dependent) diabetes mellitus.
      METHODS: 38 Type II diabetic patients, 24 with PNP (PNP+), 14 without PNP (PNP-),
      and 16 healthy control subjects were studied, first supine and subsequently
      sitting with the foot dependent for 50 mn. RESULTS: In patients with PNP, foot
      skin temperature was higher, (p<0.04) and capillary blood cell velocity (CBV,
      nailfold capillary microscopy), was lower compared to patients without PNP (222
      vs 313 micro m/s respectively, p<0.03). Compared to the control subjects, the
      percentage reduction in skin blood flux, (LDF, laser-Doppler fluxmetry), after 10
      min was higher in the PNP- and PNP+ patients (3% vs 18% and 26% respectively,
      p<0.02). These disturbances were most pronounced in PNP+ patients with a history
      of a foot ulcer. Foot swelling rate (mercury strain gauge plethysmography) in the
      first 10 min of dependency, was lower in patients with PNP+ compared to the
      control subjects (0.00165 vs 0.00286 ml.100 ml(-1)s respectively, p<0.01). In
      addition, we found a negative correlation (r=-0.41; p<0.01) between Valk-score
      (severity of PNP) and FSR. CONCLUSION/INTERPRETATION: Type II diabetes PNP is
      associated with multiple abnormalities in the (skin) microcirculation of the
      foot, characterised by reduced capillary blood flow, an enhanced reduction in
      skin blood flux and impaired fluid filtration after sitting up. The most severe
      abnormalities were observed in patients with a history of foot ulceration.

PMID- 12189448
TI  - Myocardial infarction in diabetic rats: role of hyperglycaemia on infarct size
      and early expression of hypoxia-inducible factor 1.
AB  - AIMS/HYPOTHESIS: This study aimed to evaluate the effects of hyperglycaemia on
      the evolution of myocardial infarction and the expression of the transcriptional
      factor for angiogenesis hypoxia-inducible factor 1alpha (HIF-1alpha) in the rat.
      METHODS: We studied the effects of streptozotocin induced diabetes on infarct
      size and HIF-1 alpha gene expression. These parameters were also evaluated in
      isolated hearts of non-diabetic rat, in condition of high glucose concentration.
      RESULTS: In streptozotocin (STZ)-diabetic rats (in vivo study), myocardial
      infarct size was greater (p<0.01) in hyperglycaemic rats (22 mmol/l) than in
      normoglycaemic (7 mmol/l) or non-diabetic rats. In euglycaemic conditions, basal
      expression of HIF-1alpha mRNA was not appreciable, but increased steadily after
      ischaemia (762+/-86%, p<0.001); this response was blunted in hyperglycaemic STZ
      rats (6.8+/-6% of the control, p<0.001) and improved in euglycaemic STZ-rats
      (58+/-10%). The changes in myocardial Rac1 mRNA expression paralleled those of
      HIF-1alpha. In isolated hearts from non-diabetic rats (in vitro study), perfusion
      with high glucose (33 mmol/l) produced an infarct size (58+/-2% of the area at
      risk) not different from that obtained in hyperglycaemic STZ-rats (57+/-2%).
      Similar changes in the expression of HIF-1alpha and Rac1, which were prevented by
      glutathione infusion (0.3 mmol/l) were also observed. CONCLUSION/INTERPRETATION:
      Both hyperglycaemia and high glucose concentrations increased basal HIF-1alpha
      and Rac1 expression, suggesting a state of pseudohypoxia. These findings show
      that myocardial infarct size in the rat is increased in hyperglycaemic conditions
      and is associated with a reduced expression of the HIF-1alpha gene. These changes
      are reversed, totally or partially, by normoglycaemia or glutathione suggesting a
      role for reactive oxygen species generation brought about by hyperglycaemia.

PMID- 12189449
TI  - Identification of a single nucleotide polymorphism showing no insulin-mediated
      suppression of the promoter activity in the human insulin receptor substrate 2
      gene.
AB  - AIMS/HYPOTHESIS: To understand the transcriptional regulation and to investigate
      the pathological influence upon Type II (non-insulin-dependent) diabetes mellitus
      of insulin receptor substrate 2 ( IRS2), the 5' flanking region of the human IRS2
      gene was cloned and screened in Japanese diabetic patients. METHODS: Luciferase
      reporter assay and electrophoretic mobility shift assay (EMSA) were combined in
      HepG2, Fao, RINm5F, and HeLa cells to characterise the human IRS2 promoter
      region. Single nucleotide polymorphisms (SNPs) were identified in Japanese Type
      II diabetic patients by sequencing and were genotyped. RESULTS: The proximal 2399
      bp of the 5' flanking region of the human IRS2 gene was cloned. A core promoter
      region was extended between nucleotide positions -834 and -557 (relative to the
      translation initiation site). The region [(-758)AGGGGGAGGG(-749)] that appears
      important in the positive regulation of IRS2transcription was identified by EMSA
      with (32)P-labelled double-stranded oligonucleotides encompassing regions
      protected from DNase I digestion by nuclear extract of HepG2 cells. Two SNPs (
      765 C/ T and -2062 T/ C), identified by screening Japanese Type II diabetic
      patients, were not associated with Type II diabetes. IRS2-driven reporter
      activity in the plasmid containing thymine at -765 was not suppressed by insulin
      when measured in Fao cells. CONCLUSION/INTERPRETATION: The 5' flanking sequence
      of the human IRS2 was investigated and two SNPs were identified. The SNP at -765
      was suggested to be involved in the insulin-mediated regulation of the
      transcriptional activity of IRS2.

PMID- 12189450
TI  - The SstI polymorphism of the apo C-III gene is associated with insulin
      sensitivity in young men.
AB  - AIMS/HYPOTHESIS: Insulin resistance is considered to be a risk factor for
      diabetes and coronary heart disease and is determined by the interaction between
      genetic and environmental factors. The SstI polymorphism in the apolipoprotein C
      III gene has been related to the presence of different features of the insulin
      resistance syndrome. We investigate if this mutation influences the peripheral
      effect of insulin in healthy young subjects (30 men and 29 women) eating a
      westernised diet. METHODS: We investigated peripheral insulin sensitivity with
      the insulin suppression test after a 28-day westernised high-saturated fat diet
      (38% total fat and 18% saturated fat with 115 mg of cholesterol per 1000 Ju).
      RESULTS: Steady state plasma glucose values were lower in S1-S1 compared with S1
      S2 men (p=0.018 by ANOVA), but not in women (p=0.723). CONCLUSION/INTERPRETATION:
      There was no difference between carriers and non-carriers of the S2 allele in
      relation to incidence and sensitivity; although on subgroup analysis there was an
      effect in men but not in women.

PMID- 12189451
TI  - Effects of cisapride on colonic transit in patients with progressive systemic
      sclerosis.
AB  - Progressive systemic sclerosis (PSS) may involve any portion of the
      gastrointestinal tract, including the colon. Constipation is common in patients
      with PSS. Cisapride, a benzamide derivative, is a potentially useful agent in the
      treatment of chronic idiopathic constipation. The effect of cisapride on colonic
      transit was evaluated in 16 PSS patients by a radionuclide colonic transit
      method. Each patient received cisapride orally three times a day for a week. The
      results showed acceleration in colonic transit in response to cisapride. We
      conclude that cisapride is effective in the treatment of constipation in patients
      with PSS.

PMID- 12189452
TI  - Lumbar stiffness but not thoracic radiographic changes relate to alteration of
      lung function tests in ankylosing spondylitis.
AB  - Involvement of the costovertebral (CV) and costotransverse (CT) as well as the
      sacroiliac (SI) joints is known to occur in patients with ankylosing spondylitis
      (AS). The functional significance of these changes is not clear. We have
      performed clinical and radiological evaluations and assessed the effect of joint
      involvement on pulmonary function. We detected radiologic evidence of involvement
      of the CV joint in 80% of patients and of the CT joint in 60 %. We found a direct
      relation between the severity of CV, CT and SI joint affliction, and the severity
      of CV and SI joints were related to time of evolution of the disease. Pulmonary
      function tests revealed neither restrictive nor obstructive defects. No relation
      was found between pulmonary function and CV and CT joint affliction. Patients
      with stiffer spines had a tendency to have pulmonary function tests within the
      lower limit of the normal range. In patients with AS diaphragmatic breathing
      might compensate the chest respiration to some extent.

PMID- 12189453
TI  - Assessment of quality of life of parents of children with juvenile chronic
      arthritis.
AB  - The aim of the study was to assess the quality of life (QOL) and the
      psychological status of parents of children with juvenile chronic arthritis
      (JCA). The QOL, anxiety and depression of the parents of 28 children with JCA
      were evaluated and compared to those of the parents of 28 healthy children.
      Mothers of JCA children and mothers of healthy children reported similar QOL. The
      reported anxiety and depression levels were similar for mothers and fathers in
      both groups. The parents of children with pauciarticular-type JCA reported lower
      QOL and higher levels of anxiety and depression than the parents of children with
      other types, namely polyarticular and systemic JCA. These findings may be
      explained by the fact that the pauciarticular patients had shorter disease
      duration and were less frequently seen in the outpatient clinic. The QOL of
      mothers of children with JCA was found to be slightly impaired in the group of
      children with pauciarticular JCA. Future larger studies are needed to confirm
      these results, as the number of subjects in the three groups was rather low.

PMID- 12189454
TI  - The urinary excretion of glycosaminoglycans and heparan sulphate in lupus
      nephritis.
AB  - Renal involvement in systemic lupus erythematosus (SLE) affects the disease
      outcome. In order to advance the diagnosis and the initiation of therapy, non
      invasive diagnostic techniques are required. In this study, urinary
      glycosaminoglycans (GAG) and heparan sulphate (HS) were measured in 26 patients
      with biopsy-proven lupus nephritis and compared to 16 healthy controls. Uronic
      acid as a representative of GAGs in urine was determined spectrophotometrically
      with the meta-hydroxydiphenyl, following acid treatment. HS was determined as
      hexosamine by the method of Smith and Gilkerson. The median values of GAG (3.99
      mg/g crea./day) and HS (2.41 mg/g crea./day) in patients were significantly ( P =
      0.001) higher than in the control group (1.98 and 0.87, respectively). There was
      a positive correlation between GAG and HS values ( P = 0.000, r = 0.924) in SLE
      patients. There were no differences in HS excretion, microalbuminuria and SLE-DAI
      scores between different classes of lupus nephritis. However, GAG values in class
      3 nephritis were significantly ( P = 0.033) higher than from both class 2 and
      class 4 lupus nephritis. There were no differences in all the measured parameters
      between normoalbuminuric, microalbuminuric and macroproteinuric patients.
      Furthermore, there were no correlations between GAG, HS excretions and SLE-DAI
      scores or microalbuminuria. These results suggest that urinary GAG and HS may
      serve as useful, independent and non-invasive markers of lupus nephritis.

PMID- 12189455
TI  - ACTH, cortisol and prolactin in active rheumatoid arthritis.
AB  - Prolactin (PRL) and glucocorticoids are hormones involved in the regulation of
      the immune system. Rheumatoid arthritis (RA) is an inflammatory condition that
      presents a diurnal rhythm of disease activity. ACTH, PRL, cortisol, IL-1 beta and
      TNF-alpha circadian rhythms have been studied in active RA (aRA) to evaluate a
      possible relationship between the neuroendocrine system and immunological
      activity in rheumatoid patients. ACTH, PRL, cortisol, PRL/cortisol ratio and IL-1
      beta and TNF-alpha levels were determined in aRA patients and in control subjects
      at 6.00, 10.00, 14.00, 18.00, 22.00 and 02.00 h. In aRA patients we observed
      lower ACTH and cortisol levels at 22.00 h and 2.00 h, respectively and higher PRL
      and PRL/cortisol ratio at 2.00 h when compared to controls. IL-1 beta and TNF
      alpha reached their highest serum levels in aRA patients at 2.00 and 6.00 h. This
      study provides evidence that in aRA there could be a temporary and probably
      causal relationship between diurnal disease activity, hormonal disequilibrium and
      cytokine secretion. An imbalance in favour of proinflammatory hormones (PRL and
      cytokines) as opposed to levels of anti-inflammatory hormones could be
      responsible for the diurnal rhythm of activity disease observed in aRA patients.

PMID- 12189456
TI  - Ultrasound and clinical evaluation of quadricipital tendon enthesitis in patients
      with psoriatic arthritis and rheumatoid arthritis.
AB  - Enthesitis is an inflammatory lesion of the tendon, ligament and capsular
      insertions into the bone, and it is a fundamental element in the diagnosis of
      spondyloarthropathies. Sonography is the method of choice for studying
      periarticular soft tissues because it is capable of detecting both the early
      (oedema, thickening) and late alterations (erosions and enthesophytes); it is
      also an inexpensive, biologically harmless and easily repeatable technique. The
      aim of this study was to compare the prevalence of quadricipital enthesitis in
      psoriatic arthritis (PsA) and rheumatoid arthritis (RA) patients, and to document
      any clinical and echostructural differences in this lesion between the two
      diseases. The results show that enthesitis is more frequent in PsA patients, more
      than half of whom are asymptomatic. Knee inflammation was found in the PsA
      patients with enthesitis regardless of the concomitant presence of joint
      effusion; none of the RA patients suffered from enthesitis alone. Quadricipital
      enthesitis is more frequent in male patients. There was no significant
      correlation between the presence of peripatellar psoriatic lesions and
      enthesitis. Sonographic examinations of patients with enthesitis revealed that
      those with RA had predominantly inflammatory lesions, whereas PsA patients also
      showed major new bone deposition.

PMID- 12189458
TI  - Successful treatment with low-dose weekly methotrexate in a case of
      undifferentiated spondyloarthropathy coexisting with cutaneous polyarteritis
      nodosa.
AB  - A case of a 56-year-old woman diagnosed with HLA-B27-positive undifferentiated
      spondyloarthropathy who developed cutaneous lesions consistent with cutaneous
      polyarteritis nodosa is presented. The rarity of this association and the
      dramatic response of both conditions to low-dose weekly methotrexate are
      emphasised.

PMID- 12189457
TI  - Risk period for developing osteonecrosis of the femoral head in patients on
      steroid treatment.
AB  - Patients who require long-term steroid use are at risk for the development of
      osteonecrosis. However, the risk period for developing osteonecrosis of the
      femoral head has not yet been defined. The authors attempted to determine the
      onset of osteonecrosis of the femoral head following steroid treatment. Medical
      record data of patients with steroid-related osteonecrosis of the femoral head
      from four university hospitals were reviewed. Information was collected regarding
      the duration and dose of steroid use for patients who were diagnosed at the early
      stage by magnetic resonance imaging (MRI) without positive findings on plain
      radiographs (Association Research Circulation Osseous stage I osteonecrosis).
      Twenty-two patients were diagnosed at Association Research Circulation Osseous
      stage I. There were eight male and 14 female patients ranging in age from 17 to
      60 years (mean 33). The total dose of steroid, which was used until the time of
      detection of osteonecrosis by MRI, ranged from 1800 to 15 505 mg prednisolone or
      its equivalent (mean 5928 mg). The period from the start of steroid treatment to
      the diagnosis by MRI ranged from 1 month to 16 months (mean 5.3 months). Twenty
      one of 22 patients were diagnosed within 12 months of the initiation of steroid
      treatment. The duration of steroid treatment within this period ranged from 1
      month to 12 months (mean 4.5 months). There may be a risk period of 12 months for
      developing femoral head osteonecrosis in patients receiving long-term steroid
      treatment. Close observation and more aggressive screening are recommended within
      the first year of long-term steroid treatment to prevent advanced osteonecrosis
      of the femoral head.

PMID- 12189459
TI  - Unusual localisation of chronic arthropathy in lumbar facet joints after
      parvovirus B19 infection.
AB  - Human parvovirus B19 infection may be responsible for acute and chronic
      arthropathy. We present the case of a woman, who developed a severe chronic
      parvovirus B19 infection with persistence of DNA parvovirus B19, which was
      detected in the serum by polymerase chain reaction (PCR). After intravenous
      immunoglobulin administration she noted a disappearance of the general symptoms
      and the virus became undetectable by PCR in the serum. However, 1 month later
      back pain appeared. Magnetic resonance imaging showed bilateral effusions of the
      apophyseal joints of the lumbar spine (L4-L5). Spine involvement is rarely
      described during acute or chronic parvovirus B19 infection. In this case it was
      not possible to determine whether the facet joint arthropathy was reactive or due
      to persistent articular infection, or induced by immunoglobulin therapy.

PMID- 12189460
TI  - Myelodysplastic and myeloproliferative syndromes associated with giant cell
      arteritis and polymyalgia rheumatica: a coincidental coexistence or a causal
      relationship?
AB  - A variety of systemic autoimmune disorders have been reported in patients with
      myelodysplastic and myeloproliferative syndromes. A possible association with
      polymyalgia rheumatica and giant cell arteritis has also been recognised. We
      report another case of polymyalgia rheumatica and one of giant cell arteritis
      associated with a myelodysplastic syndrome and the two first cases of giant cell
      arteritis associated with essential thrombocytaemia and chronic myelomonocytic
      leukaemia, respectively. It seems that there is a relationship between these
      entities, but the nature of this association is still unknown.

PMID- 12189461
TI  - Duodenal necrosis as the presenting manifestation of polyarteritis nodosa.
AB  - Polyarteritis nodosa involves necrotising vasculitis of small and medium-sized
      arteries. Multiple organ systems are involved. A non-specific and slow course of
      disease is common. Gastrointestinal involvement is characterised by abdominal
      pain, nausea and vomiting. Bowel infarction and perforation, cholecystitis and
      hepatic infarction are well known complications. However, bowel infarction as the
      presenting symptom of the disease is rare. The case of a 20-year-old male with
      necrosis of the duodenum heralding polyarteritis nodosa is reported. The patient
      made a slow recovery after extensive abdominal surgery and a stormy course. The
      postoperative management and treatment of polyarteritis nodosa are discussed. A
      high index of suspicion and prompt multidisciplinary approach are needed in order
      to improve survival in these rare but potentially fatal conditions.

PMID- 12189462
TI  - Cranial nerve lesions and abnormal visually evoked potentials associated with the
      M694V mutation in familial Mediterranean fever.
AB  - A 52-year-old Turkish man with familial Mediterranean fever (FMF) due to the
      homozygous M694V mutation in the MEFV-gene on chromosome 16p13.3, newly developed
      hemicrania, blurred and double vision, ptosis, ophthalmoparesis and peripheral
      facial nerve palsy. Except for double vision, all the other abnormalities
      disappeared spontaneously within 10 days after onset. Markedly prolonged
      latencies of the visually evoked potentials were also found. At follow-up, 8
      months after onset of the neurological abnormalities, right-sided
      bradydiadochokinesia, right-sided discrete weakness and right-sided hypaesthesia
      were found. After the exclusion of other hereditary fever syndromes, migraine,
      stroke, Molaret's meningitis, Behcet's syndrome and mitochondriopathy by
      clinical, serological, CSF investigations, funduscopy, electroencephalography,
      and cerebral MRI and MRI angiography, the described neurological abnormalities
      were regarded as CNS and PNS manifestation of vasculitis or amyloidosis in FMF.

PMID- 12189463
TI  - Multifocal osteonecrosis -- a case report.
AB  - The pathogenesis of idiopathic multifocal osteonecrosis is poorly understood. It
      is difficult to diagnose with conventional radiography or computed tomography and
      poses a great management challenge. A case of idiopathic multifocal osteonecrosis
      is presented in a young boy illustrating the difficulties in the management of
      such patients.

PMID- 12189464
TI  - Coincidence of Behcet's disease and SAPHO syndrome.
AB  - A young woman presented with deteriorated visual acuity due to acute retinal
      vasculitis. The diagnosis of Behcet's disease was made on the basis of the
      ophthalmologic findings and recurrent oral and genital aphthous ulcerations. In
      the past, this young woman had been operated on several times because of
      progressive aseptic osteitis of the right clavicle. The actual examination
      revealed chronic osteitis, osteosclerosis and hyperostosis of the anterior chest
      wall, as well as severe acne papulopustulosa et conglobata. These findings
      resulted in an additional diagnosis of SAPHO syndrome. This report is the first
      description of Behcet's disease occurring in association with SAPHO syndrome,
      both fulfilling the diagnostic criteria.

PMID- 12189465
TI  - Vasculitis induced by zafirlukast therapy.
AB  - Zafirlukast is a leukotriene inhibitor that has recently been approved for the
      prophylaxis of asthma. Although this new product has been well accepted because
      of its convenient dosing and relatively few side effects, several cases of Churg
      Strauss syndrome have been reported to be associated with its use. In this paper
      we describe the case of a 54-year-old white man with no history of corticosteroid
      therapy in whom leukocytoclastic vasculitis, hepatitis and eosinophilia developed
      while he was on zafirlukast therapy for mild asthma.

PMID- 12189466
TI  - Seronegative Lyme arthritis caused by Borrelia garinii.
AB  - A case of a female patient suffering from Lyme arthritis (LA) without elevated
      antibody levels to Borrelia burgdorferi sensu lato is reported. Seronegative Lyme
      arthritis was diagnosed based on the classic clinical manifestations and DNA
      detected Borrelia garinii in blood and synovial fluid of the patient, after all
      other possible causes of the disease had been ruled out. The disease was
      resistant to the first treatment with antibacterial agents. Six months after the
      therapy, arthritis still persisted and DNA of Borrelia garinii was repeatedly
      detected in the synovial fluid and the tissue of the patient. At the same time,
      antigens or parts of spirochaetes were detected by electron microscopy in the
      synovial fluid, the tissue and the blood of the patient. The patient was then
      repeatedly treated by antibiotics and synovectomy has been performed.

PMID- 12189468
TI  - A simple technique for minor salivary gland biopsy appropriate for use by
      rheumatologists in an outpatient setting.
AB  - Minor salivary gland biopsy is a potentially simple procedure with high
      diagnostic value used primarily in the diagnosis of Sjogren's syndrome. We
      summarise our experience performing a simplified biopsy procedure, which is
      modified to allow its use by rheumatologists and other non-surgical physicians in
      an outpatient setting.

PMID- 12189467
TI  - Co-occurrence of psoriatic arthritis with collagenous colitis: clinicopathologic
      findings of a case.
AB  - A 58-year-old man developed psoriatic arthritis and, after 6 months, persistent
      watery diarrhoea. Biopsies from the colorectal mucosa showed thickened
      subepithelial collagen consistent with collagenous colitis. There also was an
      inflammatory cell infiltration (mainly lymphocytes and monocytes) in the chorion.
      These findings and the parallel course of articular and bowel complaints suggest
      a clinicopathologic correlation between arthritis and colic involvement.

PMID- 12189469
TI  - Increased spore production by Glomus intraradices in the split-plate monoxenic
      culture system by repeated harvest, gel replacement, and resupply of glucose to
      the mycorrhiza.
AB  - Monoxenic culture of Glomus intraradices Schenck and Smith with Ri T-DNA
      transformed roots in two-compartment Petri dishes is a very useful technique for
      physiological studies and the production of clean fungal tissues. Experiments
      were conducted to increase the efficiency of this method for the production of
      arbuscular mycorrhizal fungus spores. Approximately 20,000 spores could be
      harvested every 2 months from the distal (fungus only) compartment of a 9-cm
      diameter divided Petri dish. The method requires replacement of the gelled media
      in the distal compartment and resupply of 200 mg glucose to the proximal (root)
      compartment coincident with harvest of spores. These modifications resulted in an
      approximate threefold increase in spore production per unit time over the
      standard split-plate culture technique.

PMID- 12189470
TI  - Arbuscular mycorrhizal relations of mangrove plant community at the Ganges river
      estuary in India.
AB  - Mangroves are climax formation of hydrohalophytes inhabiting estuarine or marine
      salt marshes in the tropics and subtropics. As a terrestrial plant community
      inhabiting tidally inundated estuarine or marine sediments, mangroves show
      considerable adaptation to salinity, water-logging and nutrient stress. Thirty
      one species of mangrove and mangrove associates and 23 species of transported
      flora, belonging to 25 families at four physiographic stages of succession of the
      mangrove plant community at the terminal part of the Ganges river estuary in
      India were examined for arbuscular mycorrhizal (AM) root association. Dominant
      members of the mangrove plant community were all AM, mostly with 'Paris' type
      structures. Many of the known non-mycotrophic plant families, except the
      Cyperaceae, also showed AM association, with intracellular hyphae and vesicles as
      the most discernible endophyte structures. Intensity of AM colonization varied
      both with the species and situations of their occurrence, being more intense and
      also more extensive in less saline dry ridge mangroves than in more saline
      formative and developed swamp mangroves. Introduced exotic trees on the ridges
      and embankments were infected by AM, but less than the declining mangroves in the
      same location. Seven species of AM fungi in common with those of the upstream
      mesophytic plants were isolated from root-free rhizosphere soils of the
      mangroves, three of which predominated in root association. These species,
      individually and as mixtures, infected roots of salinity tolerant herbs and trees
      in both locational silt and upstream alluvial soil with obvious improvements in
      their biomass yield and phosphorus nutrition. AM infective potential of root-free
      rhizosphere soils of the dominant members of the mangrove community were
      negatively related to salinity level of the sediment soil of the successional
      stages. The evidences of AM association of mangroves and other salt marsh plants
      obtained here and those reported elsewhere are discussed.

PMID- 12189471
TI  - Saprobic characteristics of three fungal taxa from ericalean roots and their
      association with the roots of Rhododendron groenlandicum and Picea mariana in
      culture.
AB  - Simultaneous associations among ectotrophic and ericoid mycorrhizal hosts and
      their mycorrhizal fungi are expected in boreal bogs where ericaceous shrubs and
      conifers coexist rooted in an organic matrix dominated by Sphagnum mosses. We
      were thus prompted to examine, in vitro, the abilities of three ericoid
      mycorrhizal fungi [ Hymenoscyphus ericae, Oidiodendron maius, and Variable White
      Taxon (VWT)] to associate with Picea mariana (Pinaceae), with both P. mariana and
      Rhododendron groenlandicum (Ericaceae) simultaneously, and to decompose Sphagnum
      fuscum. Hymenoscyphus ericae and VWT developed an intracellular association with
      roots of P. mariana and with roots of R. groenlandicum. Two strains of O. maius
      did not form typical infection units in R. groenlandicum, nor did they colonize
      the root cells of P. mariana. Mass losses incurred by sterilized S. fuscum plants
      inoculated with these three taxa indicated that O. maius could be more efficient
      as a free-living saprophyte on this material than either H. ericae or VWT and may
      in part explain why atypical associations with the roots of ericaceous hosts were
      formed.

PMID- 12189472
TI  - Colonization of roots by arbuscular mycorrhizal fungi using different sources of
      inoculum.
AB  - Arbuscular mycorrhizal fungi (AMF) form a number of different infective
      propagules that are used to form new mycorrhizal associations. These are spores,
      extraradical hyphae and infected roots. However, not all fungi are equally
      capable of colonizing roots with all of the above-mentioned propagules and there
      is conflicting evidence of major differences in colonization strategy between
      members of the Glomineae and Gigasporineae. In this study, we tested the
      abilities of eight fungal species from four different genera to colonize roots
      using three different types of inoculum. Glomus and Acaulospora isolates
      colonized from all inoculum types, whereas Gigaspora and Scutellospora isolates
      colonized mainly from spores and to a limited degree from root fragments.
      Extraradical hyphae were not suitable propagules for the species of Gigaspora and
      Scutellospora tested. This indicates that AMF have different colonization
      strategies and that this is largely differentiated at the suborder level. It is
      unclear why there is such a difference among the fungi in inoculum types. Future
      research should examine differences in the anatomy and physiology to discern a
      mechanism for such differences in life-history strategies.

PMID- 12189473
TI  - Improved tolerance of maize plants to salt stress by arbuscular mycorrhiza is
      related to higher accumulation of soluble sugars in roots.
AB  - The effect of colonization with the arbuscular mycorrhizal (AM) fungus Glomus
      mosseae (Nicol. & Gerd.) Gerdemann & Trappe on the growth and physiology of NaCl
      stressed maize plants ( Zea mays L. cv. Yedan 13) was examined in the greenhouse.
      Maize plants were grown in sand with 0 or 100 mM NaCl and at two phosphorus (P)
      (0.05 and 0.1 mM) levels for 34 days, following 34 days of non-saline pre
      treatment. Mycorrhizal plants maintained higher root and shoot dry weights.
      Concentrations of chlorophyll, P and soluble sugars were higher than in non
      mycorrhizal plants under given NaCl and P levels. Sodium concentration in roots
      or shoots was similar in mycorrhizal and non-mycorrhizal plants. Mycorrhizal
      plants had higher electrolyte concentrations in roots and lower electrolyte
      leakage from roots than non-mycorrhizal plants under given NaCl and P levels.
      Although plants in the low P plus AM fungus treatment and those with high P minus
      AM fungus had similar P concentrations, the mycorrhizal plants still had higher
      dry weights, soluble sugars and electrolyte concentrations in roots. Similar
      relationships were observed regardless of the presence or absence of salt stress.
      Higher soluble sugars and electrolyte concentrations in mycorrhizal plants
      suggested a higher osmoregulating capacity of these plants. Alleviation of salt
      stress of a host plant by AM colonization appears not to be a specific effect.
      Furthermore, higher requirement for carbohydrates by AM fungi induces higher
      soluble sugar accumulation in host root tissues, which is independent of
      improvement in plant P status and enhances resistance to salt-induced osmotic
      stress in the mycorrhizal plant.

PMID- 12189474
TI  - Mycorrhiza-induced differential response to a yellows disease in tomato.
AB  - The protective effects induced by arbuscular mycorrhizal (AM) fungi against a
      phytoplasma of the Stolbur group have been investigated in tomato by morphometry
      and flow cytometry. Symptoms induced by the phytoplasma were less severe when the
      plants also harboured AM fungi. Morphological parameters such as shoot and root
      fresh weight, shoot height, internode length, leaf number and adventitious root
      diameter were closer to those of healthy plants when arbuscular mycorrhiza were
      present. Reduced nuclear senescence was observed in AM plants infected with
      phytoplasmas; the percentages of nuclear populations with different ploidy levels
      were intermediate between AM and phytoplasma-infected plants. The mechanisms
      underlying these interactions are discussed and a direct action of the AM fungus
      is hypothesized.

PMID- 12189475
TI  - The arbuscular mycorrhizal fungus Glomus geosporum in European saline, sodic and
      gypsum soils.
AB  - Plants of saline and sodic soils of the Hungarian steppe and of gypsum rock in
      the German Harz mountains, thus soils of high ionic strength and electric
      conductivity, were examined for their colonization by arbuscular mycorrhizal
      fungi (AMF). Roots of several plants of the saline and sodic soils such as
      Artemisia maritima, Aster tripolium or Plantago maritima are strongly colonized
      and show typical AMF structures (arbuscules, vesicles) whereas others like the
      members of the Chenopodiaceae, Salicornia europaea, Suaeda maritima or
      Camphorosma annua, are not. The vegetation of the gypsum rock is totally
      different, but several plants are also strongly colonized there. The number of
      spores in samples from the saline and sodic soils examined is rather variable,
      but high on average, although with an apparent low species diversity. Spore
      numbers in the soil adjacent to the roots of plants often, but not always,
      correlate with the degree of AMF colonization of the plants. As in German salt
      marshes [Hildebrandt et al. (2001)], the dominant AMF in the Hungarian saline and
      sodic soils is Glomus geosporum. All these isolates provided nearly identical
      restriction fragment length polymorphism (RFLP) patterns of the internal
      transcribed spacer (ITS) region of spore DNA amplified by polymerase chain
      reaction (PCR). Cloning and sequencing of several PCR products of the ITS regions
      indicated that ecotypes of the G. geosporum/ Glomus caledonium clade might exist
      at the different habitats. A phylogenetic dendrogram constructed from the ITS or
      5.8S rDNA sequences was nearly identical to the one published for 18S rDNA data
      (Schwarzott et al. 2001). It is tempting to speculate that specific ecotypes may
      be particularly adapted to the peculiar saline or sodic conditions in such soils.
      They could have an enormous potential in conferring salt resistance to plants.

PMID- 12189476
TI  - Arbuscular mycorrhizas in cycads of southern India.
AB  - Root and soil samples of three potted or ground-grown cycads ( Cycas circinalis,
      C. revoluta, Zamiasp.) were collected between November 1999 and June 2000 and
      surveyed for arbuscular mycorrhizal (AM) colonization and spore populations. AM
      fungi were associated with all root systems and rhizosphere samples examined.
      Root colonization was of a typical Arum type and AM colonization levels differed
      significantly between species and between potted and ground-grown cycads.
      Mycorrhizal colonization levels were inversely related to root hair number and
      length. Spores of nine morphotypes belonging to three genera ( Acaulospora,
      Glomus, Scutellospora) were extracted from soil. The percentage root length
      colonized by AM fungi was not related to soil factors, but total AM fungal spore
      numbers in the rhizosphere soil were inversely related to soil nitrogen and
      phosphorus levels. AM fungal spore numbers in the soil were linearly related to
      root length colonized. The co-occurrence of septate non-mycorrhizal fungi was
      recorded for the first time in cycads. These observations and the relationship
      between plant mycorrhizal status and soil nutrients are discussed.

PMID- 12189477
TI  - A mycorrhiza-responsive protein in wheat roots.
AB  - A small protein, designated Myk15, was found to be strongly induced in wheat (
      Triticum aestivum) roots colonized by the arbuscular mycorrhizal fungus Glomus
      intraradices. This protein, which is most abundant in root fractions
      characterized by strong mycorrhizal colonization, has been characterized using
      two-dimensional polyacrylamide gel electrophoresis and microsequencing. It has an
      apparent molecular mass of 15 kDa and an isoelectric point of 4.5. The N-terminal
      sequence has high similarity to a peptide sequence deduced from an expressed
      sequence tag (EST) clone derived from Medicago truncatula roots colonized by G.
      intraradices. This EST clone is predicted to code for a protein with a similar
      size and isoelectric point as Myk15. The N-terminus of the deduced M. truncatula
      protein contains a highly hydrophobic stretch of 24 amino acid residues preceding
      the region with high similarity to the Myk15 N-terminus. This hydrophobic stretch
      is predicted to form a transmembrane alpha-helix and may correspond to a
      cleavable targeting domain.

PMID- 12189478
TI  - Impact of pneumoperitoneum on tumor growth.
AB  - AIM OF THE STUDY: To compare intraperitoneal tumor growth after CO2 laparoscopy
      (L), gasless laparoscopy (GL), midline laparotomy (ML), and general anesthesia
      (GA) as a control. MATERIALS AND METHODS: A prospective randomized trial was
      carried out in nude rats. A carcinomatosis was obtained by intraperitoneal
      injection of either one of the two human ovarian cancer cell lines IGR-OV1 or
      NIH:OVCAR-3. Rats secondly underwent randomly different kind of procedures: CO2 L
      (8 mmHg, 60 min), GL (traction by a balloon for 60 min), ML (bowel removed and
      let on a mesh for 60 min), or GA. The rats were finally killed 10 or 35 days
      after surgery (respectively in IGR-OV1, or NIH:OVCAR-3 models). Tumor growth was
      assessed by the weight of the omental metastasis and MIB1 immunostaining.
      Peritoneal dissemination as well as abdominal wall metastases were assessed by
      pathological examination. Statistical analysis used the chi-square test (or
      Fisher exact test) and Bonferroni method for multiple comparison between groups.
      RESULTS: Fifteen rats were included in each group. Mean omental weight was
      significantly increased after surgery (3.1 to 5.6 g), when compared to control
      (2.4 g), but no significant difference was recorded between the three surgical
      accesses. MIB1 immunostaining was poor in the PNP group (37%), whereas it was
      higher after midline laparotomy (51%), but the difference was not significant (p
      = 0.07). Similarly, no significant variation was recorded in the NIH:OVCAR-3
      model for omental weight or MIB1 staining. CO2 pneumoperitoneum significantly
      increased right diaphragmatic dome involvement in the NIH:OVCAR-3 model.
      Abdominal wall metastases were significantly more frequent after surgery when
      compared to the control group, but no significant difference could be
      demonstrated between surgical groups in each model. CONCLUSION: In these solid
      tumor models, CO2 pneumoperitoneum had no deleterious effect on tumor growth when
      compared to gasless laparoscopy or midline laparotomy.

PMID- 12189479
TI  - Comparison of laparoscopic versus conventional technique in colonic and liver
      resection in a tumor-bearing small animal model.
AB  - BACKGROUND: Laparoscopic procedures in oncological surgery are either done in
      curative or palliative intent. We present two experiments comparing laparoscopic
      to conventional surgery in the curative and palliative setting regarding short
      term (stress and immune alteration) and long-term aspects (survival time and
      recurrence rate). METHODS: We established two syngenic tumor-bearing small animal
      models for curative liver resection (Morris hepatoma 3924A, ACI rats) and
      palliative colon resection (BSp73 ASML, BOX rats). Male rats were operated on,
      performing laparoscopic and conventional liver resection as well as laparoscopic
      and conventional colon resection; control groups (anesthesia) were included. The
      following parameters of the stress and immune system were measured:
      corticosterone, neopterine, Il-1-b, Il-6, and body weight as a parameter of
      postoperative recovery. Analyzed long-term parameters were survival time, tumor
      weight, and recurrence rate (histology). RESULTS: After colon resection, analysis
      of variance showed significant differences in all short-term parameters,
      including body weight after laparoscopic versus conventional colon resection (p
      <0.05). In the case of laparoscopic versus conventional liver resection, only Il
      6 showed globally statistically significant differences for the short-term
      parameters (p = 0.05). Long-term parameters were not significantly different
      between the laparoscopic and conventional groups, regardless of the type of
      resection (colon or liver) or the operative setting (curative or palliative).
      However, there were differences after curative liver resection compared to the
      control group (anesthesia alone). CONCLUSION: These results suggest that the type
      of intraabdominal operation (colon or liver) may influence the degree of trauma
      of an operation more than the type of technique (laparoscopic or open). The
      perioperative alteration of stress and immune function has no implications on the
      long-term results, such as survival time or recurrence, neither in the curative
      nor in the palliative setting. The thesis that laparoscopic surgery results in
      less pain, which in turn means less stress and less alteration of the immune
      system and therefore results in a lower rate of postoperative metastasis is only
      valid for laparoscopic colonic resection in our model. The part of the thesis
      that states that fewer metastases should occur after laparoscopic oncological
      surgery cannot be confirmed in our study.

PMID- 12189480
TI  - Impact of laparoscopic CO2-insufflation on tumor-associated molecules in cultured
      colorectal cancer cells.
AB  - BACKGROUND: Laparoscopic CO2-insufflation is believed to stimulate proliferation
      and metastatic potential of gastrointestinal carcinomas. E-cadherin, I-CAM1, I
      CAM2, and CD44 are involved into the metastatic process of different cancer cell
      lines. The current study investigates the influence of CO2-insufflation on the
      expression of E-cadherin, I-CAM1, I-CAM2, and CD44 in vitro. METHODS: CX-2 and
      CC531 colon carcinoma cells (human/rat) were exposed to pneumoperitoneal CO2
      insufflation. E-cadherin, I-CAM1, I-CAM2, and CD44 were measured 0, 12, 24, 48,
      and 72 h after CO2-insufflation using flowcytometry. Control groups were exposed
      to room air. Data were analyzed by the Wilcoxon-Mann-Whitney U-test. RESULTS:
      Both cell lines showed significant alteration in E-cadherin, I-CAM1, and CD44
      expression after CO2 exposure (p <0.05). No significant differences were found
      regarding I-CAM2 expression. CONCLUSION: The present study demonstrates CO2
      insufflation to influence the expression of E-cadherin, I-CAM1 and CD44. Whether
      these changes increases the metastatic potential of colorectal cancer cells in
      vivo needs further investigation.

PMID- 12189481
TI  - A new device for the detection and recognition of blood vessels in laparoscopic
      surgery.
AB  - BACKGROUND: The recognition and localization of blood vessels to prevent their
      intraoperative perforation poses a major problem in laparoscopic surgery. The
      endoscopic pulse detector is a new device that has been specially developed for
      the detection and recognition of blood vessels in laparoscopic surgery. The
      instrument uses an accelerometer to detect a pulse, and it is inexpensive and
      simple to use. The aim of this study was to investigate the performance and
      possibilities of the new instrument. METHODS: The instrument's performance and
      features were tested in laboratory conditions by use of simulated circulation. We
      assessed the dependence of the signal amplitude recorded by the instrument over a
      given blood vessel on the blood pump frequency change (36-130/min), circulating
      systolic pressure change (40-180 mm Hg), and adjacent blood vessel pulsations.
      Clinically, the instrument was tested in a randomized study in 40 elective
      noncomplicated laparoscopic cholecystectomies, where we assessed the time needed
      for the preparation of Calot's triangle and positioning of the cystic artery.
      RESULTS: The results of laboratory testing showed that the instrument operated
      throughout the frequency range of 36-130/min and a circulating systolic pressure
      range of 40-180 mmHg, while the signal amplitude rose with pressure increase. The
      results of clinical testing showed that use of the pulse detector in laparoscopic
      cholecystectomy significantly reduced the time needed to prepare Calot's triangle
      (t = 3.91; df = 38; p <0.001) and also made the positioning of the cystic artery
      more reliable. CONCLUSION: The study showed the new instrument to be very simple
      to use and potentially valuable in laparoscopic surgery, primarily for the
      differentiation of blood vessels of similar structures.

PMID- 12189482
TI  - Endoscopic totally preperitoneal ventral hernia repair.
AB  - BACKGROUND: In order to combine the advantages of a minimal invasive approach
      with a retromuscular mesh implantation, we developed an endoscopic totally
      preperitoneal approach for the treatment of ventral hernias. METHODS: The
      surgical technique is described with the accent on preoperative marking of mesh
      surface, the retromuscular insertion of the first trocar, the extraperitoneal
      dissection, the reduction of the hernia sac, and the choice and insertion of the
      mesh. RESULTS: Fifteen patients have been operated. Complete reduction of the
      hernia sac could be accomplished in five. In eight, the peritoneum was incised at
      the hernia neck. A polypropylene mesh was used in six cases. In the others, ePTFE
      or a composite mesh was used. Circumferential fixation with a tacker was
      performed. No major complications were seen. No mesh needed to be removed. One
      recurrence was seen 5.5 months postoperatively with a median follow-up period of
      126 days. CONCLUSIONS: This new endoscopic technique takes advantage of immediate
      mesh fixation by the peritoneal sac and may avoid the potential complications
      related to the transabdominal approach and intraabdominal position of the mesh. A
      further long-term evaluation is necessary.

PMID- 12189483
TI  - Reduced acute phase response after laparoscopic total extraperitoneal bilateral
      hernia repair compared to open repair with the Stoppa procedure.
AB  - BACKGROUND: Although laparoscopic hernia repair has been shown to be associated
      with less postoperative pain and an earlier recovery, there is still controversy
      about its role in hernia surgery. In general, laparoscopy produces less trauma to
      tissues than open surgery. This has been reflected by the reduced acute phase
      inflammatory response observed after laparoscopic surgery compared to open
      surgery in various settings, such as cholecystectomy or hysterectomy. The aim of
      this study was to evaluate the acute phase response after bilateral hernia repair
      by comparing the open Stoppa procedure with the laparoscopic totally
      extraperitoneal prosthetic repair (TEPP). METHODS: Patients were randomly
      allocated to either technique after written informed consent was obtained.
      Measurements were made of complete blood count, erythrocyte sedimentation rate
      (ESR), C-reactive protein (CRP), interleukin-1b (IL-1b), IL-6, and tumor necrosis
      factor-a (TNF-a) preoperatively and 4, 24, and 48 h postoperatively. VAS pain
      scores, consumption of analgesics, and delay before resumption of normal
      activities were also recorded. All the procedures were performed under general
      anesthesia by or in the presence of the same surgeon. RESULTS: Thirty-nine
      patients were included: 19 underwent the Stoppa procedure and 20 had a
      laparoscopic repair. The two groups were well matched for age, sex, ASA score,
      and preoperative values. The operation took longer (p <0.001) in the group
      undergoing TEPP. Patients resumed their normal activities earlier (p <0.05) after
      laparoscopy. In the open group, there was a larger decrease of the lymphocyte
      count after 4 (p <0.01) and 24 h (p = 0.04); an increased elevation of ESR after
      48 h (p = 0.02); a larger increase of IL-6 after 4 (p = 0.05), 24 (p = 0.003),
      and 48 h (p <0.001); and a larger increase in CRP after 24 (p = 0.05) and 48 h (p
      = 0.01). There was no morbidity. There was no difference in postoperative IL-1b,
      TNF-a, total white blood cell count, polymorphonuclear count, VAS for pain, or
      need for analgesics between the two groups, except on the operative day.
      CONCLUSIONS: The acute phase inflammatory response in clearly more active after
      the open Stoppa procedure than after TEPP, indicating that the former is
      associated with increased tissue trauma. This may play a role in the earlier
      recovery seen after the TEPP procedure.

PMID- 12189484
TI  - DNA hypermethylation: when tumour suppressor genes go silent.
AB  - The phenotype of the cancerous cell may arise either from genetic alterations
      that disrupt gene function through sequence modifications (mutations) or
      epigenetic events that may alter the heritable state of gene expression (i.e.
      without changing the actual sequence of the genome). Whereas mutations in certain
      tumour suppressor genes are most often thought of in association with their
      inactivation during cancer initiation or progression, epigenetic alterations such
      as DNA methylation appear to be tightly linked to the sequential non-reversible
      events of normal tissue differentiation and organogenesis. This highlights a link
      between tissue differentiation and tumourigenesis with respect to the stable
      nature of certain epigenetic changes. In the case of tumourigenesis, both genetic
      and epigenetic mechanisms of altered gene expression often go hand in hand; not
      surprisingly, biallelic inactivation of a given tumour suppressor gene may occur
      via a combination of mutational and epigenetic events and is entirely consistent
      with the Knudson two-hit hypothesis of tumourigenesis. This review summarizes
      recent developments within the field of DNA methylation, highlighting its
      association with the transcriptional silencing of tumour suppressor genes in a
      variety of human cancers.

PMID- 12189485
TI  - Major gene evidence after MTHFR-segregation analysis of serum homocysteine in
      families of patients undergoing coronary arteriography.
AB  - Elevated levels of homocysteine is a risk factor for coronary artery disease.
      Polymorphic alleles in the MTHFR genes that cause recessively inherited increased
      homocysteine level can explain only a small proportion of the observed variation
      in homocysteine level. To investigate additional genetic influences, we examined
      environmental, familial, and genetic influences on serum homocysteine levels in
      661 family members of 112 probands who underwent elective coronary arteriography.
      Maximum likelihood methods were used to fit several genetic and non-genetic
      models of inheritance to these data to determine if an unobserved Mendelian major
      gene could explain the familial homocysteine distribution. Adjustments for age,
      lifestyle (smoking and alcohol consumption), serum folate and vitamin B12, and
      the measured genotype effect of the MTHFR C677T mutation was carried out
      separately for males and females using multiple regression models for
      homocysteine, before and after log-transformation prior to this segregation
      analysis. After excluding the effects of mutations in the MTHFR genes, we found
      evidence of a major gene acting in a co-dominant manner. Estimated mean
      homocysteine levels for the three putative genotypes (LL, LH, and HH) were 8.0,
      10.1, and 15.9 micro mol/l, respectively, with relative frequencies of 56.8%,
      37.2%, and 6%, respectively. Our analysis suggested the presence of a co
      dominantly expressed major gene, in addition to the effects of the MTHFR C677T
      mutation. The results of this study also indicated that multifactorial
      inheritance was supported more strongly than Mendelian inheritance alone. Our
      findings may have implications for attempts to identify new homocysteine
      susceptible genes.

PMID- 12189487
TI  - Progressive hearing loss, and recurrent sudden sensorineural hearing loss
      associated with GJB2 mutations--phenotypic spectrum and frequencies of GJB2
      mutations in Austria.
AB  - Mutations of GJB2 (encoding connexin 26) are the most common cause of hearing
      loss (HL) in different populations, and a broad spectrum of GJB2 mutations has
      been identified. We screened 204 consecutive patients with non-syndromic
      sensorineural hearing loss for GJB2 mutations. Causative GJB2mutations were
      identified in 31 (15.2%) patients, and two common mutations, c.35delG and L90P
      (c.269T>C), accounted for 72.1% and 9.8% of GJB2 disease alleles. In four
      additional patients (2.0%) only one recessive GJB2 mutation was identified,
      making genetic counselling difficult. No genotype-phenotype correlation was
      established. We found, however, that homozygotes for truncating mutations were
      more likely to have a more severe degree of HL compared with other genotypes.
      Moreover, we showed by co-segregation studies that L90P is a GJB2 disease allele,
      and that compound heterozygotes for L90P and any recessive mutation share a mild
      to moderate phenotype. GJB2-associated HL was linked with progressive HL or with
      recurrent sudden sensorineural hearing loss (SSNHL) in three of 15 cases being
      analysed retrospectively. We extended the phenotypic spectrum of GJB2-related
      disease and recommend GJB2 mutation screening also in cases of progressive HL,
      and recurrent SSNHL. In addition, a carrier frequency of 1/110 (0.9%) for the
      most common Caucasian mutation in this gene, c.35delG, was determined in 1,212
      blood donors from West-Austria, supporting the prevailing hypothesis of a
      Mediterranean founder mutation. Based on population and patient data, an overall
      GJB2 mutation carrier frequency of 1.3% was estimated for West-Austria.

PMID- 12189486
TI  - FOXP2: novel exons, splice variants, and CAG repeat length stability.
AB  - FOXP2 is a transcription factor containing a polyglutamine tract, a zinc-finger
      motif, and a forkhead DNA-binding domain. The FOXP2 gene is located on 7q31. A
      missense mutation in the forkhead domain (exon 14) and a balanced reciprocal
      translocation t(5;7)(q22;q31.2) with a breakpoint between exons 3b and 4 have
      recently been associated with a speech and language disorder (SPCH1). The role of
      FOXP2 in this neurodevelopmental disorder suggests that mutations in FOXP2 could
      cause other neuropsychiatric disorders. To begin investigation of this
      possibility, we examined the genomic structure and CAG/CAA repeat region of
      FOXP2. We detected little polymorphism and no expansions in the FOXP2 CAG/CAA
      repeat in 142 individuals with progressive movement disorders. We found evidence
      of alternate splice variants and six previously undetected exons: three 5'
      untranslated exons (s1, s2, s3), two additional untranslated exons (2a and 2b)
      between exons 2 and 3, a translated exon (4a) between exons 4 and 5, and a longer
      version of exon 10 (10+) that contains an alternate stop codon and produces a
      truncated protein (FOXP2-S). Our results suggest that FOXP2 spans at least 603 kb
      of genomic DNA, more than twice the previously defined region, and provide
      evidence of a promoter region flanking exon s1. This demonstration of additional
      FOXP2 exons and splice variants should facilitate understanding of FOXP2 function
      and the search for additional FOXP2 mutations.

PMID- 12189488
TI  - Functional characterization of the new human GABA(A) receptor mutation
      beta3(R192H).
AB  - We screened 124 individuals for single nucleotide polymorphisms of the alpha1,
      beta3 and gamma2 genes of the GABA(A) receptor in the regions corresponding to
      the ligand-binding domains on the protein level. In a patient with chronic
      insomnia, a missense mutation was found in the gene of the beta3 subunit. This
      mutation results in the substitution of the amino acid residue arginine for
      histidine in position 192 (beta3(R192H)). The patient was found to be
      heterozygous for this mutation. Functional analysis of human
      alpha1beta3(R192H)gamma2S GABA(A) receptors using ultra fast perfusion techniques
      revealed a slower rate of the fast phase of desensitization compared with
      alpha1beta3gamma2S GABA(A) receptors. Additionally, current deactivation [a major
      determinant of inhibitory postsynaptic current (IPSC) duration] was faster in the
      mutated receptors. This raises the possibility of decreased GABAergic inhibition
      contributing to insomnia, as some members of the patient's family also suffer
      from insomnia. The mutation beta3(R192H) might, therefore, be linked to this
      condition. The intron/exon boundaries of the alpha1 subunit gene were also
      established and three additional variants were found in the alpha1 and beta3
      genes.

PMID- 12189489
TI  - Unexpectedly high prevalence of the mild form of propionic acidemia in Japan:
      presence of a common mutation and possible clinical implications.
AB  - Propionic acidemia [MIM 606054] is a form of organic acidemia caused by genetic
      deficiency of propionyl-CoA carboxylase (PCC) and characterized by attacks of
      severe metabolic acidemia and hyperammonemia beginning in the neonatal period or
      in early infancy. There are, however, patients who have higher PCC activities and
      present later with unusual symptoms, such as mild mental retardation or
      extrapyramidal symptoms, sometimes even without metabolic acidosis. Through the
      neonatal screening of more than 130,000 Japanese newborns we detected a frequency
      of patients with propionic acidemia more than ten times higher than previously
      reported, most of them with milder phenotypes. The mutational spectrum was quite
      different from that of patients with the severe form and there was a common
      mutation (Y435C) in the beta subunit of the PCC gene (PCCB). Since patients with
      the mild form could present with unusual symptoms and therefore could easily
      remain unrecognized, it is important to identify those patients and clarify their
      natural history. Molecularly, one of the mutations (A1288C) caused an unusual
      pattern of multiple exon skipping and another unidentified mutation lead to the
      absence of mRNA. Taking into consideration previous findings regarding PCCB
      mutations, it appears that this gene is particularly prone to posttranscriptional
      modifications such as missense mediated exon skipping, mRNA decay, or rapid
      product degradation.

PMID- 12189490
TI  - Androgen receptor CAG polymorphism and prostate cancer risk.
AB  - Recent studies have suggested that polymorphisms of the androgen receptor gene (
      AR) may influence the risk of prostate cancer (PC) development and progression.
      Here, we analyzed the length of the CAG repeat of the AR gene in 1363
      individuals, including patients with PC, benign prostate hyperplasia (BPH), and
      population controls. There was a tendency for short CAG repeats to be associated
      with PC. The Odds Ratio (OR) for PC was 1.47 ( P=0.05) when individuals with
      short CAG repeats (</=18) were compared with those having long repeats (>18). CAG
      repeat length was not significantly associated with family history, disease
      stage, grade, age at diagnosis, prostate-specific antigen (PSA) level at
      diagnosis, or prognosis of the patients. Unexpectedly, short CAG repeats were
      significantly less common in patients with BPH compared with controls (OR=0.47,
      P=0.03). Our results suggest that the CAG polymorphism of the AR gene is unlikely
      to have a major role in the development or progression of PC in the Finnish
      population. The association of CAG repeats with the risk of BPH warrants further
      study.

PMID- 12189491
TI  - Evolution of a VNTR located within the promoter region of the thiopurine
      methyltransferase gene: inferences from population and sequence data.
AB  - The promoter region of the human thiopurine methyltransferase (TPMT) gene
      contains a variable number of tandem repeats (VNTR) with three kind of motifs (A,
      B, and C) differing by the length of the unit core and nucleotide sequence. We
      have studied the structural variation within the VNTR alleles in two human
      populations and in samples from gorillas and chimpanzees. In humans, no
      intermingling of motifs was detected within the VNTR, and the sequences of the
      three core motifs remained remarkably unchanged, differences between alleles
      corresponding essentially to variations in the number of A and B repeats. The
      variation pattern in humans is consistent with an interpretation in which two
      contiguous genetic units (repeats A and B) behave evolutionarily according to the
      stepwise mutation model, as inferred from the population distribution profiles
      and from the molecular phylogenetic relationships among the VNTR alleles.
      However, the observation of a strong negative correlation between the numbers of
      A and B repeats also suggests that the regularity and/or independence of the
      mutational process has been disrupted to some extent by interactions between the
      A and B stretches. Selective pressure (the VNTR plays some role, although minor,
      in the TPMT function) or biased mutation are possible explanations. In gorillas
      and chimpanzees, several A-, B-, or C-like motifs were detected, but their
      arrangement within the VNTR alleles did not followed the regular pattern
      registered in humans and, particularly for the B-like motifs, a considerable
      sequence hypervariability was registered. Furthermore, the structural differences
      among non-human alleles were sufficiently numerous to render more plausible the
      assumption of the infinite allele model.

PMID- 12189492
TI  - Organization of the human liver carnitine palmitoyltransferase 1 gene ( CPT1A)
      and identification of novel mutations in hypoketotic hypoglycaemia.
AB  - Carnitine palmitoyltransferase 1A (CPT1A) deficiency is a rare autosomal
      recessive disorder of mitochondrial fatty acid oxidation. CPT1 controls the
      import of long-chain fatty acids into the mitochondria, where they are oxidized.
      Two CPT1 isoforms, the so-called "liver" and "muscle" CPT1s encoded by the
      CPT1Aand CPT1Bgenes, respectively, have been identified so far. While the cDNA
      sequences of both isoforms are known, only CPT1Bgene organization has yet been
      described. We took advantage of the working draft data to characterize the
      organization of the human CPT1A gene. We have shown the existence of 20 exons,
      spanning 60 kb of DNA. Two alternate promoters and numerous transcription factor
      binding sites were identified within the 5' upstream region of the gene. In the
      3' untranslated region, the major polyA signal was suggested to lie about 2 kb
      downstream of the stop codon. These data enabled us to characterize six novel
      mutations in four CPT1A-deficient patients; namely Q100X (exon 4), A414 V (exon
      11), Y498C (exon 13), 1876-1G>A (intron 15), a 113-bp intronic insertion in the
      mature CPT1A mRNA (exon 13-14 junction), and a large 8-kb deletion encompassing
      intron 14 to exon 17. Thus, identification of the CPT1A gene organization
      contributes to improve the molecular screening in patients and provides tools for
      the study of the human CPT1A gene expression.

PMID- 12189493
TI  - Human connexin26 (GJB2) deafness mutations affect the function of gap junction
      channels at different levels of protein expression.
AB  - Mutations in the connexin26 (GJB2) gene account for about half of inherited non
      syndromic deafness cases in Western countries. The connexin26 protein is a
      subunit of gap junctions that form a network of intercellular communication among
      supporting cells and fibrocytes in the mammalian inner ear. Here we describe
      functional implications of mutations in the coding region of connexin26 genes
      (M1V, M34T, L90P, R127H, F161S, P173R, and R184P), identified in patients and
      stably transfected in human HeLa cells. While all mutated connexin26 cDNAs were
      transcribed, only M34T, L90P, R127H, F161S, and R184P were translated in HeLa
      cells. Analysis of indirect immunofluorescence showed membranous localization,
      strong for M34T, L90P, R127H, and very weak for F161S, but no signal
      corresponding to M1V, P173R and R184P. Tracer coupling experiments revealed
      diffusion of microinjected neurobiotin into neighbouring cells in the case of
      M34T and R127H, whereas M1V, L90P, F161S, P173R and R184P mutants did not show
      intercellular coupling. The results of oligomerisation studies suggested a partly
      disturbed assembly of hemichannels in M34T and L90P mutants but complete absence
      of hemichannel formation in the R184P mutant. The R127H mutation did not affect
      channel formation and is likely to represent a polymorphism. Our results show
      that mutations in the connexin26 gene can affect gap junctional intercellular
      communication at the level of protein translation, trafficking or assembly of
      hemichannels.

PMID- 12189494
TI  - SOX10 mutations in chronic intestinal pseudo-obstruction suggest a complex
      physiopathological mechanism.
AB  - The type IV Waardenburg syndrome (WS4), also referred to as Shah-Waardenburg
      syndrome or Waardenburg-Hirschsprung disease, is characterised by the association
      of Waardenburg features (WS, depigmentation and deafness) and the absence of
      enteric ganglia in the distal part of the intestine (Hirschsprung disease).
      Mutations in the EDN3, EDNRB, and SOX10 genes have been reported in this
      syndrome. Recently, a new SOX10 mutation was observed in a girl with a neural
      crest disorder without evidence of depigmentation, but with severe constipation
      due to a chronic intestinal pseudo-obstruction and persistence of enteric
      ganglia. To refine the nosology of WS, we studied patients with typical WS4
      (including Hirschsprung disease) or with WS and intestinal pseudo-obstruction. We
      found three SOX10 mutations, one EDNRB and one EDN3 mutations in patients
      presenting with the classical form of WS4, and two SOX10 mutations in patients
      displaying chronic intestinal pseudo-obstruction and WS features. These results
      show that chronic intestinal pseudo-obstruction may be a manifestation associated
      with WS, and indicate that aganglionosis is not the only mechanism underlying the
      intestinal dysfunction of patients with SOX10 mutations.

PMID- 12189495
TI  - Evidence for a gene influencing heart rate on chromosome 4 among hypertensives.
AB  - While mechanisms are poorly understood, resting heart rate has been shown to be a
      strong predictor of the risk of cardiovascular disease, cancer, and all-cause
      mortality. We performed a genome scan for quantitative trait loci influencing the
      resting heart rate among 962 Caucasians and 1,124 African-Americans in the
      Hypertension Genetic Epidemiology Network (HyperGEN), a multi-center study of
      genetic and environmental factors related to hypertension. The NHLBI Mammalian
      Genotyping Service typed a total of 391 anonymous microsatellite markers, spaced
      roughly equally throughout the genome. Within each race and sex, heart rate was
      adjusted for covariates, including age, age(2), study center, body mass index,
      beta-blocker use, alcohol consumption, smoking, number of city blocks walked per
      day, and number of hours watching television. Genome scans were performed using
      variance component linkage analysis as implemented by GENEHUNTER (version 2) for
      each race, using race-specific marker allele frequencies derived from random
      samples. The highest lod score detected in Caucasians was 2.14 on chromosome 4
      (at 195.06 cM); a lod score of 1.14 was found at the same locus among the African
      Americans, and a lod score of 3.18 resulted when the two racial groups were
      combined. Evidence was also found on chromosome 10 to support a recent report of
      an association between heart rate and the beta1 adrenergic receptor. The
      suggestive evidence for linkage found on chromosome 4 in both Caucasian and
      African-American hypertensive sib pairs indicates that further investigation on
      that region may be warranted to locate a gene influencing variability in resting
      heart rate.

PMID- 12189496
TI  - Megalencephalic leukoencephalopathy with subcortical cysts; a founder effect in
      Israeli patients and a higher than expected carrier rate among Libyan Jews.
AB  - Megalencephalic leukoencephalopathy with subcortical cysts (MLC) is a progressive
      inherited neurological disorder characterized by macrocephaly, deterioration in
      motor functions and cerebellar ataxia. In Israel the disease is found in an
      increased frequency among Libyan Jews. The disease is caused by mutations in the
      MLC1 gene, which encodes a putative CNS membrane transporter. We describe three
      novel mutations (p.G59E, p.P92S, and 134_136insC) in seven MLC families. One of
      these mutations, p.G59E, was found in the vast majority of MLC patients in
      Israel. Screening of 200 normal Libyan Jewish individuals for the p.G59E
      mutation, revealed a carrier rate of 1/40 compared with an expected carrier rate
      of 1/81. Several explanations could account for this difference the most likely
      one is an admixture of the Libyan Jewish population.

PMID- 12189497
TI  - Functional characterization of a natural variant of luteinizing hormone.
AB  - Luteinizing hormone (LH) plays an important role in the gametogenesis in both
      sexes by promoting the production of sex steroid hormones in the testes and
      ovaries. We previously described a genetic variant (V) of LH resulted from a
      mutation (G1502A) in the LH beta-subunit gene, causing the glycine102serine
      change in the protein hormone. This variant was subsequently found to be
      associated with both male and female infertility. In this study, we determined
      the functional aspect of this LH variant in vitro. Site-directed mutagenesis was
      employed to construct the V-LH beta-subunit gene. Bioactivities of V-LH expressed
      in Chinese hamster ovary (CHO) cells cotransfected with the V-beta-subunit and
      native alpha-subunit genes were compared to those of wild-type (WT) LH. The amino
      acid replacement did not result in the change of efficacy of alpha- and beta
      subunit dimerization of the hormone. However, V-LH had significantly lower
      receptor-binding activity (P<0.001) and lower biopotency for progesterone
      production (P<0.001) than WT-LH at the higher concentrations of LH. Considering
      the latter and its known association with both male and female infertility, it is
      suggested that the V-LH may be a contributing factor to the pathogenesis of
      infertility in the carriers of this variant.

PMID- 12189498
TI  - The WHO/ISUP 1998 and WHO 1999 systems for malignancy grading of bladder cancer.
      Scientific foundation and translation to one another and previous systems.
AB  - Recently, two new classification systems for grading of urothelial neoplasms have
      been published. The objective of both was to avoid the overdiagnosis of cancer
      and to create better criteria for the grades. The WHO/ISUP classification of 1998
      distinguishes papilloma, papillary urothelial neoplasm of low malignant potential
      (PUNLMP), low and high grade carcinomas, whereas the WHO 1999 system subdivides
      the high grade into grades II and III, and is otherwise identical. This note
      summarizes studies supporting the rationale of the two new systems, describes
      pattern recognition criteria for the grades, and highlights the homology between
      them.

PMID- 12189499
TI  - Urothelial papillary (exophytic) neoplasms.
AB  - The contemporary classification and grading of human papillary urothelial
      neoplasms remains unsettled, with multiple recent suggestions by groups of
      pathologists with little or no clinical input. One of the chief motivations for
      these new approaches was to avoid use of the term "cancer" for neoplasms with a
      low likelihood of invasion, recurrence, and death. Also, critics contended that
      earlier grading schemes were too imprecise to be clinically useful. We summarize
      the work carried out by the majority of members of Committee No. 1 at the
      International Consultation on the Diagnosis of Non-Invasive Urothelial Neoplasms
      held in Ancona, Italy (11-12 May 2001). Our deliberations represent a
      multidisciplinary international effort based on the best available data and the
      perception of existing practical methods of classification by clinicians,
      pathologists, and cancer registrars. The WHO 1973 classification for papillary
      urothelial neoplasms (papilloma, grade 1, grade 2, and grade 3 carcinoma) is
      still superior to all existing alternatives (such as WHO/ISUP 1998 and WHO 1999),
      although some refinement of diagnostic criteria would be useful. Some
      pathologists may prefer additionally to report synonymous classification in other
      schemes, but this is discouraged owing to variations and difficulties in
      translations.

PMID- 12189500
TI  - Toker cells are probably precursors of Paget cell carcinoma: a morphological and
      ultrastructural description.
AB  - The present paper documents an investigation of the morphology,
      immunohistochemistry, and ultrastructure of Toker cells (TC), aiming for a better
      definition of these elements and better understanding of their histogenesis. We
      studied 12 nipples removed for nipple adenoma from twelve patients and a case of
      supernumerary nipple. In addition four cases of Paget's carcinoma (PC) restricted
      to the nipple without underlying tumor were studied for comparison. All cases
      were stained with hematoxylin and eosin (H&E), Alcian blue pH 2.5 and periodic
      acid-Schiff (PAS) preceded by diastase digestion and with immunohistochemistry
      using antisera anti cytokeratin 7, cytokeratin 20, protein S100, GCDFP-15, c-Erb
      B2, CAM 5.2, and epithelial membrane antigen (EMA). Two cases from the nipple
      adenoma series were studied by electron microscopy. In seven cases within the
      series of 12 nipple adenomas as well as in the case of supernumerary nipple,
      keratin 7 antibody highlighted numerous cells located within the nipple epidermis
      which in three cases showed dendritic processes. These same elements were also
      positive with CAM 5.2. All these same elements were negative with Alcian Blue
      (AB), PAS and the other antisera employed. Ultrastructural examination
      demonstrated that these cells differed from keratinocytes while they presented
      the same features as the glandular cells seen in the related nipple adenoma. The
      cells constituting Paget's carcinoma showed more irregular nuclei and were more
      easily seen in the context of the epidermis. The immunocytochemical profile of
      the cancer cells was similar to that of TC, but in addition the neoplastic cells
      were c-Erb-B2 and EMA positive in all cases, and one case also displayed numerous
      cells immunoreactive with anti GCDFP-15 antibody. Keratin 7 highlighted dendritic
      cells in two cases and AB, PAS was negative in all patients. The
      immunocytochemical profile and the ultrastructural features of TC are similar to
      those of the glandular cells constituting the ducts and the adenoma. These
      findings together with the localization of TC near or around the openings of the
      lactiferous sinuses indicate that TC might be ductal cells with a dendritic
      aspect and migrate through the galactophorous ostia. PC cells not related to
      ductal carcinomas have a similar but not superimposable immunohistochemical
      profile to TC, and in two cases the neoplastic elements were also dendritic which
      suggests that these same cells are likely to be the neoplastic counterpart of TC.

PMID- 12189501
TI  - Complex formation of IQGAP1 with E-cadherin/catenin during cohort migration of
      carcinoma cells. Its possible association with localized release from cell-cell
      adhesion.
AB  - In histopathological sections, it is frequently observed that carcinoma cells
      invade the stroma as coherent cell nests rather than single cells. We have called
      this type of movement "cohort migration (CM)" and developed an in vitro model, in
      which human colon carcinoma cells move as coherent cell sheets when stimulated
      with hepatocyte growth factor/scatter factor (HGF/SF). In this CM model,
      localized release from cell-cell adhesion at the lower portion of cells is
      essential for cell movement. Its mechanism was investigated in this study with
      special reference to the E-cadherin/catenin complex (Ecc) and IQGAP1. IQGAP1 is a
      target molecule of Cdc42 and Rac1 and negatively regulates the Ecc-based cell
      cell adhesion by dissociating alpha-catenin, a key molecule that links Ecc to
      actin cytoskeleton, from Ecc. In our study, the amount of IQGAP1 bound to Ecc
      increased in migrating cells in association with a decrease in the alpha-catenin
      level in Ecc. In accordance with this, IQGAP1 showed a shift from the cytosol to
      the membrane fraction. Moreover, confocal laser microscopic study demonstrated
      the localization of IQGAP1 at the membranes of the lower portion of migrating
      cells, where cell-cell adhesion was specifically disrupted during CM.
      Furthermore, when HGF/SF-induced CM was enhanced with pre-coated extracellular
      matrix (ECM) components, the level of IQGAP1 in Ecc increased more than that
      caused by HGF/SF alone. On the contrary, when CM was inhibited by interrupting
      cell-ECM interaction, the level of IQGAP1 in Ecc did not increase despite HGF/SF
      stimulation. Taken together, these results indicate close association of IQGAP1
      with localized disruption of cell-cell adhesion during CM and that modulation of
      CM by cross-talk between signals induced by HGF/SF and cell-ECM interactions also
      involves IQGAP1-related mechanisms.

PMID- 12189502
TI  - INK4a-ARF alterations and p53 mutations in primary and consecutive squamous cell
      carcinoma of the head and neck.
AB  - BACKGROUND: The INK4a-ARF (CDKN2A) locus, located on chromosome 9p21, encodes two
      functionally distinct tumor suppressor genes, p14(ARF) and p16(INK4a), that play
      active roles in the p53 and Rb tumor suppressive pathways, respectively. We
      analyzed the alterations of p14(ARF), p16(INK4a) and p53 to study the
      contribution of each pathway in tumorigenesis of 29 patients with primary and
      consecutive (second primary) squamous cell carcinoma of the head and neck
      (HNSCC), with a total of 68 carcinomas. METHODS: After microdissection, the DNA
      of 29 primary and 39 consecutive squamous cell carcinomas was analyzed for INK4a
      ARF inactivation and p53 mutation by means of DNA sequence analysis, methylation
      specific polymerase chain reaction (MSP), restriction-enzyme-related polymerase
      chain reaction (RE-PCR), multiplex RT-PCR and immunohistochemistry. In addition,
      microdeletions of p14(ARF) and p16(INK4a) were assessed using differential PCR.
      RESULTS: Altogether inactivation (methylation, loss of heterozygosity and
      mutation of exon 1beta) of p14(ARF) was found in 29 of all 68 (43%) carcinomas,
      with a significant difference in primary [8 of 29 (28%)] relative to second
      primary carcinomas [21 of 39 (54%)]. Methylation of p16(INK4a) occurred in 22 of
      68 (32%) carcinomas with an even distribution among primary and consecutive
      tumors. Only two (secondary) carcinomas showed simultaneous promoter methylation
      of p14(ARF) and p16 (INK4a). Mutations of p53 were found in 32 of 68 HNSCCs
      (44%), evenly distributed among primary and recurrent carcinomas. p14(ARF)
      alterations showed no relationship to p53 mutations. CONCLUSIONS: Our data
      indicate that the INK4a-ARF-/p53 pathway was disrupted in 58 of 68 (84%) primary
      and recurrent tumors, either by p53 mutations or by INK4a-ARF inactivation.
      p14(ARF) methylation occurred independently of p16(INK4a) alterations and showed
      no correlation to p53 mutations. The significantly higher rate of p14(ARF)
      alterations in recurrent (respective second primary) carcinomas suggests a
      further acquired genetic aberration during the development of the recurrent
      carcinomas.

PMID- 12189503
TI  - Disparity between mucosal and serum IgA and IgG in Helicobacter pylori infection.
AB  - Mucosal IgA and IgG are involved in the immune defense against Helicobacter
      pylori in infected patients. In contrast to IgG, IgA is transported into the
      gastric lumen and is responsible for the first-line defense. Therefore antigens
      recognized by mucosal IgA are possible candidates for vaccination. This study
      compared the IgA and IgG immune response to H. pylori in the gastric mucosa and
      that in the serum of 21 patients with H. pylori gastritis by the immunoblotting
      technique. In particular, mucosal IgA immune response against the urease antigen
      of H. pylori was studied in detail, as vaccination with this antigen was not
      curative in men. The results show that mucosal IgA was not represented by serum
      IgA and IgG, and that the H. pylori specific mucosal IgA and IgG immune responses
      differ in antigen-recognition pattern. This disparity may reflect the different
      transport ways and functions of these two immunoglobulin isotypes. Furthermore,
      mucosal IgA specific for urease was found inconsistently in patients with H.
      pylori gastritis. As vaccination antigens should induce an appropriate mucosal
      IgA immune response against H. pylori, our findings may have important
      implications for the selection of antigens for vaccination against H. pylori.

PMID- 12189504
TI  - The pagetoid variant of bladder urothelial carcinoma in situ A
      clinicopathological study of 11 cases.
AB  - Pagetoid urothelial carcinoma in situ (CIS) is a rare variant of bladder cancer
      that is characterized by an intraepithelial proliferation of large cells arranged
      singly or in clusters and randomly distributed. These neoplasms deserve
      recognition and attention, chiefly because they may be overlooked or misdiagnosed
      as urothelial dysplasia, then causing unsuspected tumor recurrence after surgery.
      We report on the clinicopathological features and immunohistochemical findings of
      11 (14.86%) cases of pagetoid CIS in a retrospective study of 74 cases of
      conventional carcinoma in situ. Most patients were male ( n=10). Their ages
      ranged from 31 years to 78 years. The lesion can be present with primary ( n=2)
      or secondary ( n=9) CIS. Pagetoid CIS is usually a focal lesion occurring in a
      clinical and histological setting of conventional CIS, and these patients
      essentially have the same progression and survival rates as patients without
      pagetoid changes and are treated in the same way. In cases with extensive
      urothelial denudation, pagetoid CIS may be focally present in otherwise normal
      looking urothelium, thus alerting the pathologist to search for additional CIS
      elsewhere in the bladder. Given that primary extramammary Paget disease of the
      external genitalia and of the anal canal may extend to the bladder and,
      conversely, some bladder cases of pagetoid CIS may extend to the urethra, ureter,
      and beyond to the external genitalia, the differential diagnoses between these
      two entities represent an important therapeutic consideration. Our data suggest
      that a panel of immunostains including CK7+/CK20+/TM+ may assist in
      differentiating urothelial pagetoid CIS from extramammary Paget disease which is
      known to be CK7+/CK20-.

PMID- 12189506
TI  - The virtual case: a new method to completely digitize cytological and
      histological slides.
AB  - The purpose of this study was to present a new method for handling
      histological/cytological cases. Thanks to the introduction of information
      technology in pathology, including the amenities afforded by robotic microscopes
      and digital imaging, tissue slides can be represented and evaluated using digital
      techniques in order to construct virtual cases through completely automated
      procedures. A virtual case (VC) is composed of a collection of digital images
      representing a histological/cytological slide at all magnification levels
      together with all relevant clinical data. In the present study, we describe an
      automated system to manage robotic microscope and image acquisition for the
      proper construction of VCs. These can then be viewed on a computer by means of an
      interface ("user-friendly") that allows one to select the more appropriate fields
      and to examine them at different magnifications, rapidly going from panoramic
      views to high resolution and vice versa. In comparison with glass slides, VCs
      have several advantages arising from their digital nature and can be considered a
      common platform for a wide range of applications such as teleconsultation,
      education, research, and quality control and proficiency tests.

PMID- 12189505
TI  - Anaplastic plasmacytoma with malignant pleural effusion lacking evidence of
      monoclonal gammopathy.
AB  - A case of plasmacytoma of the pleural cavity is reported with massive malignant
      pleural effusion, which, most unusually, lacked monoclonal gammopathy, thereby
      making it difficult to distinguish from lymphoma. The pleural tumor and pleural
      effusion contained large mononuclear lymphoma-like cells with distinct nucleoli.
      Immunohistochemistry revealed neither lymphoma markers nor clonal cytoplasmic nor
      cell surface immunoglobulins. Tumor cells were stained with vimentin and the
      plasma cell markers, VS38c, CD138 (syndecan-1), and MUM1 antibodies. Bone marrow
      contained small amounts of tumor consisting of similar cells. Electron microscopy
      showed well developed rough endoplasmic reticulum and peripherally positioned
      nuclei with euchromatin. Flow cytometry of bone marrow revealed a minimal
      involvement of CD38-positive cells. Chromosomal analysis of marrow cells revealed
      a complex abnormal karyotype. A polymerase chain reaction demonstrated clonal re
      arrangement of the immunoglobulin heavy-chain gene. The overall results indicate
      a clonal expansion of tumor cells with primitive plasma cell differentiation with
      the highly unusual feature of absent monotypic immunoglobulin. The study
      illustrates the need for a comprehensive array of techniques to distinguish such
      rare non-synthesizing and non-secretory plasmacytomas from lymphoma.

PMID- 12189507
TI  - The basement membrane-type heparan sulfate proteoglycan (perlecan) in
      ameloblastomas: its intercellular localization in stellate reticulum-like foci
      and biosynthesis by tumor cells in culture.
AB  - The localization and biosynthesis of basement membrane-type heparan sulfate
      proteoglycan (HSPG), known as perlecan, were studied in ameloblastomas using
      surgical tissue sections and cells in primary culture to demonstrate the
      existence of extracellular matrix (ECM) molecules in the intercellular space of
      epithelial tissue. HSPG was immunolocalized in the intercellular spaces of
      stellate reticulum-like cells and small vacuolar structures between basal cells
      in tumor cell nests as well as in myxofibrous stroma. By means of in-situ
      hybridization, mRNA signals for the HSPG core were intensely demonstrated in the
      cytoplasm of basal and parabasal cells of parenchyma. Furthermore, the in-vitro
      biosynthesis of HSPG core protein by ameloblastoma cells was confirmed using
      immunofluorescence, immunoprecipitation, and reverse-transcriptase polymerase
      chain reaction (RT-PCR). The results indicated that ameloblastoma cells
      synthesize HSPG and deposit it in their intercellular space. The intercellular
      HSPG might act as a carrier for transport of nutrients to tumor cells within
      ameloblastomatous foci.

PMID- 12189508
TI  - Prognostic impact of metallothionein on oral squamous cell carcinoma.
AB  - Metallothionein (MT), a low-molecular-weight protein with high cysteine content,
      seems to be related to neoplastic resistance to oncologic treatment and therefore
      has been studied as a prognostic factor for a variety of human malignant tumors.
      MT overexpression in neoplasms of ectodermal origin is usually associated with a
      poor prognosis. MT expression was evaluated in 60 samples of oral squamous cell
      carcinoma by immunohistochemistry to study its prognostic influence on oral
      cancer. Possible associations of MT immunoexpression were also investigated with
      respect to clinical stage (TNM), histological grading, and proliferation index
      (Ki-67) of the lesions. No significant statistical correlation was observed among
      these variables. The impact on overall survival was assessed by uni and
      multivariate statistical tests. Mean MT labeling index was 60%. High MT labeling
      indexes (over 76%) predicted shorter survival in univariate statistical analysis.
      In multivariate analysis, MT labeling index and clinical stage were independent
      prognostic factors. MT overexpression in oral squamous cell carcinoma seems to be
      related to a worse prognosis for patients.

PMID- 12189509
TI  - Enhancement of immunoreactivity for endothelin-1 and endothelin-converting enzyme
      1 in the cadmium-treated rat thoracic aorta.
AB  - Male rats received daily intraperitoneal injections of cadmium sulfate (2.0
      mg/kg) for 3, 6, and 8 days (cadmium-treated groups) or physiological saline for
      8 days (control group). The thoracic aortae from both groups were used for
      electron microscopy and immunocytochemistry for big endothelin (ET)-1, ET-1 and
      ET-converting enzyme (ECE)-1, and the blood plasma and homogenized thoracic
      aortae were prepared for assays of big ET-1 and ET-1 concentrations. A remarkable
      increase in the number of Weibel-Palade (WP) bodies, enhanced immunoreactivities
      for ET-1 and ECE-1 along the endothelium, and elevated concentrations of ET-1 in
      the blood plasma as well as in homogenized thoracic aortae were observed in the
      cadmium-treated groups. However, immunoreactivity for big ET-1 and the plasma and
      aortic tissue concentrations of big ET-1 did not show any significant changes
      between the control and cadmium-treated groups. By immunoelectron microscopy,
      immunoreactivities for ET-1 and ECE-1 were much more pronounced in the increased
      WP bodies. Since WP bodies are involved in the extracellular release of ET-1 in
      the manner of a regulated pathway, these findings indicate that cadmium
      administration induces the enhanced release of ET-1, which is actively processed
      by ECE-1 in the WP bodies.

PMID- 12189510
TI  - Abnormalities detected in metaphase chromosomes in bladder carcinoma: prognostic
      value and comparison with histopathological factors.
AB  - The objective of this study was to detect the incidence and prognostic value of
      chromosomal aberrations in metaphase chromosomes (hypodiploidy, hyperdiploidy
      and/or structural abnormalities) in Ta and T1 transitional cell carcinoma (TCC)
      of the bladder. Of 266 patients, the metaphase chromosomes of the primary tumour
      were studied using a direct microscopic analysis and classified into two
      categories: normal and abnormal. Recurrence and progression were prospectively
      recorded during a median follow-up period of 40 months and in a retrospective
      analysis compared with other prognostic factors. Chromosomal abnormalities were
      found in 48% of Ta tumours and in 92% of T1 tumours. In univariate analysis,
      chromosomal abnormalities were associated with recurrence-free survival ( P=0.03)
      and progression-free survival ( P=0.01). In multivariate analysis, chromosomal
      abnormalities (RR=1.98) and age (RR=0.64) were independent predictors of
      recurrence-free survival but not progression-free survival.

PMID- 12189511
TI  - Follicular dendritic cell sarcoma of the breast.
AB  - Extranodal follicular dendritic cell sarcoma (FDCS) is an extremely uncommon
      tumor with only a single case arising in the breast having been reported. We
      describe the clinico-pathological features of an additional FDCS of the lower
      outer quadrant of the right breast in a 40-year-old woman. The tumor showed three
      patterns of growth, i.e., diffuse, myxoid and fascicular. The neoplastic cells
      were large, polygonal, with a slightly eosinophilic cytoplasm and oval or
      convoluted nuclei. They were intermingled with small lymphocytes, plasma cells
      and a few bizarre multinucleated giant cells. In the fascicular areas, the cells
      were spindled, while in the myxoid areas they showed a dendritic-like appearance,
      with long cytoplasmic processes. Mitoses were numerous and often atypical. The
      neoplastic cells were intensely immunoreactive for CD21, S-100 protein and
      epithelial membrane antigen, and focally for CD35, CD68 and cytokeratins.
      Polymerase chain reaction analysis did not reveal any Epstein Barr virus genome
      in the neoplastic tissue. Electron microscopy highlighted numerous
      interdigitating cytoplasmic processes with intercellular junctions of the
      serrated, immature desmosomal or undifferentiated types. The post-surgical course
      of the patient was uneventful and she is currently free of disease 19 months
      after surgery.

PMID- 12189512
TI  - A brief history of the Society for Histochemistry: its founders, its mission and
      the first 50 years.

PMID- 12189513
TI  - The path that RNA takes from the nucleus to the cytoplasm: a trip with some
      surprises.
AB  - It is now clear that nuclear context is playing an essential role in gene
      expression. For this reason we have developed methods to study gene expression in
      situ. Transcription takes place in discrete foci in the nucleoplasm of mammalian
      cells. These sites concentrate several RNA polymerases II and factors involved in
      the production of mRNA. Moreover, these sites also contain the active machinery
      to carry out protein synthesis. Once the mRNA leaves the transcription site, it
      interacts with the nuclear pore complex and the mRNA is exported using the
      filaments of the nuclear pore complex in to the middle part of the nuclear pore
      complex and finally is released in the cytoplasm.

PMID- 12189514
TI  - Genomes, proteomes, and dynamic networks in the cell nucleus.
AB  - Post-genome era experimental strategies seek to understand cellular pathways
      globally rather than through examination of individual components. Genomics and
      proteomics provide the experimental tools to establish the framework of gene and
      protein pathways present in a cell. These methods are complemented by emerging in
      vivo microscopy approaches, which permit placement of pathways within the
      architectural context of the cell. Analysis of dynamic live cell microscopy data
      combined with computational analyses finally allows the quantitative, mechanistic
      description of protein properties and pathways operating in living cells. Here we
      discuss how genomics and proteomics are changing the study of the cell nucleus
      and how in vivo microscopy methods have contributed to our changing conceptual
      and mechanistic understanding of nuclear architecture and function. Mapping of
      gene loci and genome regions are beginning to reveal organizational principles of
      the genome within the cell nucleus, proteomic analysis of subnuclear compartments
      and the gene expression machinery is providing insights into the molecular nature
      of nuclear events, and in vivo microscopy is illuminating the dynamic nature of
      nuclear organization. Initial findings from these efforts make clear that nuclear
      and cellular behavior can not be described by linear pathways. New tools such as
      computational modeling are providing evidence that emerging concepts such as
      network organizations and stochastic interactions are crucially important for
      cellular function and organization. These insights are changing our view of the
      nucleus and the cell as a whole.

PMID- 12189515
TI  - Rapid association of cytoskeletal remodeling proteins with the developing
      phagosomes of human neutrophils.
AB  - Phagocytosis of opsonized particles by neutrophils involves highly localized
      alterations in the actin cytoskeleton that result in the formation of prominent
      pseudopodia and the phagocytic cup. Immunofluorescence microscopy was employed to
      monitor the distribution of several proteins that can regulate the cytoskeleton
      in human neutrophils undergoing phagocytosis of opsonized Candida albicans. The
      small GTPase Cdc42, its inhibitory subunit Rho-GDI, the adapter protein Nck,
      gamma-p21-activated protein kinase (gamma-Pak), and cofilin were found to undergo
      rapid association with the developing phagosomes in these cells. In contrast,
      these signaling proteins were either diffusely distributed in the cytoplasm or
      enriched in focal points at the base of the cell when optical sections were
      obtained from regions of the cell not involved in phagocytosis. These results are
      consistent with Cdc42 being critically involved in initiating the early events in
      phagocytosis by its ability to activate Pak and the Wiskott-Aldrich Syndrome
      protein that triggers the localized polymerization of actin. These data provide
      insights into the molecular mechanisms that trigger changes in the actin
      cytoskeleton during phagocytosis.

PMID- 12189516
TI  - Modulation of cytokeratin expression during in vitro cultivation of human hepatic
      stellate cells: evidence of transdifferentiation from epithelial to mesenchymal
      phenotype.
AB  - The embryonal origin of hepatic stellate cells (HSCs), the principal cells in
      hepatic fibrogenesis, is still intriguing. To explore the origin and the
      differentiation of HSCs, we studied the expression of cytokeratin 18 (CK18) and
      19 (CK19), the standard markers of simple epithelial cells, in cultured human
      HSCs. Hepatic stellate cells were isolated from five normal human livers. In
      immunofluorescence staining, both clone C-51 anti-CK18 antibody and clone RCK108
      anti-CK19 antibody labeled almost all stellate cells in the primary culture.
      Double immunofluorescence staining for cytokeratin/vimentin and cytokeratin/alpha
      smooth muscle actin detected by confocal laser scanning microscopy clearly
      demonstrated the localization of cytokeratin immunoreactivity in human HSCs.
      During subsequent cultivation of human HSCs to the tenth passage,
      immunocytochemical staining and western blot analysis demonstrated gradually
      decreasing profiles of CK18 and CK19 expression. The progressive reduction of
      cytokeratin expression was further confirmed in a culture of clone cells
      originated from a single HSC. In conclusion, both CK18 and CK19 are expressed in
      cultured human HSCs, and the extent of their expression decreases gradually
      during prolonged cultivation. Our results suggest that HSCs may be of epithelial
      origin, and that they undergo the transdifferentiation from epithelial to
      mesenchymal phenotype during an activation process in vitro.

PMID- 12189517
TI  - Expression of junction-associated proteins differentiates mouse intestinal M
      cells from enterocytes.
AB  - The intestinal lymphoid follicles and associated structures are specialised
      antigen sampling and inductive sites of the mucosal immune system. The overlying
      follicle-associated epithelium (FAE) includes the specialised antigen sampling M
      cells that are also exploited as a route of pathogen invasion. In this
      immunohistochemical study we analysed the junctional complexes of the mouse
      intestinal FAE. Protein expression at this site resembled that of other simple
      epithelia. Specifically, claudin-1/3 and ZO-1 were detected in the tight
      junctions, E-cadherin, alpha-, beta- and gamma-catenin, vinculin, alpha-actinin
      and polymerised actin were associated with the adherens junctions and the
      desmosomes were labelled with a desmosomal protein probe. These markers failed to
      reveal cell type-associated variations in the tight junctions and desmosomes. In
      contrast, M cell adherens junctions were distinguished by enhanced expression of
      beta-catenin, alpha-actinin, polymerised actin and, in some areas, E-cadherin. In
      addition, M cell junctions exhibited increased expression of intercellular
      adhesion molecule-1 and phosphotyrosine, and the M cell apical surfaces displayed
      characteristic patterns of beta-catenin, alpha-actinin and actin expression. We
      have thus partially defined the junctional complexes of mouse intestinal FAE and
      identified M cell-specific characteristics that may further explain the biology
      and function of this unique cell type.

PMID- 12189518
TI  - Microbial-host interactions specifically control the glycosylation pattern in
      intestinal mouse mucosa.
AB  - The glycosylation of the intestinal cell layer is thought to control several key
      functions of the gut such as vectorial transports, defence against microbial
      agents or immunological processes. It has been assumed that the gut microflora
      may modulate the glycosylation pattern of the intestinal cell layer. However,
      there is no direct evidence for this regulatory process. The first goal of this
      work was to establish the germ-free mice intestinal glycosylation baseline using
      a histochemical approach and a panel of ten lectins with defined glycan
      specificities to tissue sections prepared from various cellular compartments of
      the small and large intestine. Using this baseline, we have studied the
      contribution of the gut microflora on the carbohydrate composition of
      glycoconjugates of intestinal cells by comparing the germ-free and conventional
      mice glycosylation patterns. Analysis of the germ-free mice intestinal
      glycosylation baseline revealed that the expression of glycans depends on the
      proximodistal gradient (small to large intestine) and on the cell lineage
      (absorptive, goblet, crypt, and Paneth cells), indicating that mice are able to
      create and maintain a strict topological and cell lineage-specific regulation of
      glycosyltransferase expression. By comparing germ-free and conventional mice, we
      find that the gut microflora specifically modulates the gut glycosylation
      pattern, quantitatively as well as qualitatively by changing the cellular and
      subcellular distribution of glycans. This is the first report in mice to directly
      demonstrate the critical contribution of microflora to intestinal glycosylation,
      a key characteristic of the gut.

PMID- 12189519
TI  - CuZn-superoxide dismutase in human thymus: immunocytochemical localisation and
      secretion in thymus-derived epithelial and fibroblast cell lines.
AB  - CuZn-superoxide dismutase (SOD) plays a key role in mediating the cellular
      response to oxidative stress. Its expression in normal thymus was investigated by
      immunohistochemical techniques and CD3-, CD68- and cytokeratin-specific staining,
      in order to identify thymocytes, macrophages and epithelial components.
      Immunocytochemical studies showed an overall CuZn-SOD thymic distribution with a
      prevailing concentration within thymic medulla. The analysis of CuZn-SOD release
      by thymus-derived epithelial and fibroblast cell lines showed the ability of both
      cell lines to release the anti-oxidant enzyme, especially in the presence of
      stress conditions as represented by serum and nutrient deprivation. These data
      suggest that CuZn-SOD could be a relevant antioxidant paracrine molecule in human
      thymus.

PMID- 12189520
TI  - Desmin and actin alterations in human muscles affected by delayed onset muscle
      soreness: a high resolution immunocytochemical study.
AB  - Lack of staining for desmin in muscles in animal models of eccentric exercise has
      been suggested to reflect disruption of the desmin intermediate filament network
      and proposed to cause disruption of the myofibrillar apparatus and deterioration
      of muscle fibers. In a recent study, we examined muscle biopsies from persons who
      had performed different eccentric exercise protocols, which induced delayed onset
      muscle soreness (DOMS). We were unable to verify that loss of staining for desmin
      was a feature of sore muscles. Nevertheless, we observed changes in the desmin
      cytoskeleton, but the meaning of the observations was not conclusive. In the
      present study, a high resolution immunocytochemical method was used to
      investigate the changes of desmin and actin in human muscles following a bout of
      eccentric exercise that lead to DOMS 2-3 days post-exercise. Biopsies were taken
      before exercise and 1 h and 2-3 and 7-8 days after exercise. Phalloidin, a ligand
      that labels filamentous actin, and anti-desmin antibodies were used to stain
      semithin (approximately 0.5 micro m) cryosections. At 1 h post-exercise, the
      staining of actin and desmin did not differ from the controls, whereas in
      biopsies taken 2-3 and 7-8 days after exercise, 12.5% (SD 5.8%) and 6.1% (SD
      2.3%) fibers showed areas of increased staining for actin. Corresponding values
      for fibers with increased staining for both actin and desmin were 8.7% (SD 3.9%)
      and 11.4% (SD 4.6%), respectively. We suggest that the increased staining of
      actin and desmin reflects an increased synthesis of these proteins as part of an
      adaptation process following the unaccustomed eccentric exercise.

PMID- 12189521
TI  - Lentiviral-mediated gene delivery in human monocyte-derived dendritic cells:
      optimized design and procedures for highly efficient transduction compatible with
      clinical constraints.
AB  - Gene delivery to dendritic cells (DCs) could represent a powerful method of
      inducing potent, long-lasting immunity. Although recent studies underline the
      intense interest in lentiviral vector-mediated monocyte-derived DC transduction,
      efficient gene transfer methods currently require high multiplicities of
      infection and are not compatible with clinical constraints. We have designed a
      strategy to optimize the efficiency and clinical relevance of this approach.
      Initially, using a third generation lentiviral vector expressing green
      fluorescent protein, we found that modifying the vector design, the DC precursor
      cell type, and the DC differentiation stage for transduction results in sustained
      transgene expression in 75-85% of immature DCs (transduction at a multiplicity of
      infection of 8). This high efficiency was reproducible among different donors
      irrespective of whether DCs were expanded from fresh or cryopreserved CD14(+)
      precursors. We then developed procedures that bypass the need for highly
      concentrated lentiviral preparations and the addition of polybrene to achieve
      efficient transduction. DCs transduced under these conditions retain their
      immature phenotype and immunostimulatory potential in both autologous and
      allogeneic settings. Furthermore, genetically modified DCs maintain their ability
      to respond to maturation signals and secrete bioactive IL-12, indicating that
      they are fully functional. Finally, the level of transgene expression is
      preserved in the therapeutically relevant mature DCs, demonstrating that there is
      neither promoter-silencing nor loss of transduced cells during maturation. The
      novel approach described should advance lentiviral-mediated monocyte-derived DC
      transduction towards a clinical reality.

PMID- 12189522
TI  - Evaluation of E1B gene-attenuated replicating adenoviruses for cancer gene
      therapy.
AB  - Gene-attenuated replication-competent adenoviruses are emerging as a promising
      new modality for the treatment of cancer. For the aim of improving adenoviral
      vectors for cancer gene therapy, we have constructed genetically attenuated
      adenoviral vectors with different combinations of E1B genes and investigated the
      possibility of enhanced oncolytic and replication effects of these engineered
      replication-competent adenoviruses. We show here that the cytolytic potency of
      each gene-attenuated replicating adenovirus differed significantly depending on
      the presence or deletion of E1B 55 kDa and E1B 19 kDa function. More
      specifically, among the constructed vectors (Ad-deltaE1B19, Ad-deltaE1B55, Ad
      deltaE1B19/55, and Ad-wt), E1B 19 kDa-inactivated adenovirus (Ad-deltaE1B19) was
      the most potent against all tumor cells tested, inducing the largest-sized
      plaques and marked CPE. Further, cells infected with either Ad-deltaE1B19 or
      E1B19/55 kDa-deleted adenovirus (Ad-deltaE1B19/55) showed complete cell lysis
      with disintegrated cellular structure, whereas cells infected with Ad-wt
      maintained intact cellular and nuclear membrane with properly structured
      organelles. TUNEL and DNA fragmentation assay also revealed that the Ad
      deltaE1B19 or Ad-deltaE1B19/55 adenovirus-infected cells showed more profound
      induction of apoptosis in comparison to wild-type adenovirus-infected cells. The
      presence of E1B 55 kDa gene was required for efficient viral replication and
      deletion of E1B 19 kDa function in replicating adenovirus-induced apoptosis,
      leading to increased cytopathic effects. Moreover, Ad-deltaE1B19 adenovirus
      showed a better antitumor effect than other E1B-attenuated adenoviruses. Taken
      together, the replicating adenoviruses deleted in E1B 19 kDa function may serve
      as an improved vector for anticancer gene therapy in combination with apoptosis
      inducing modalities such as chemotherapeutic agents and radiation therapy.

PMID- 12189523
TI  - Hematoprotection and enrichment of transduced cells in vivo after gene transfer
      of MGMT(P140K) into hematopoietic stem cells.
AB  - The overexpression of mutant forms of O(6)-methylguanine-DNA-methyltransferase
      (MGMT), resistant to the MGMT inhibitor O(6)-benzylguanine (BG), protects
      hematopoietic cells from the toxicity of combined BG plus O(6)-alkylating agent
      chemotherapy. To evaluate the feasibility of this approach for clinically
      relevant O(6)-alkylating agents, combined therapy with BG and two
      chloroethylnitrosourea-type drugs, ACNU or BCNU, or the triazene derivative
      temozolomide (TMZ) was investigated in a murine bone marrow transplant model
      allowing transgenic expression of the highly BG-resistant MGMT(P140K) mutant.
      Whereas 20/20 control animals transplanted with nontransduced cells died of
      progressive myelosuppression during therapy, nearly all animals transplanted with
      MGMT(P140K)-transduced cells survived treatment with BG/ACNU (12/15), BG/TMZ
      (10/10), or BG/BCNU (5/5). In surviving animals, hematological parameters
      improved during chemotherapy and pretreatment levels were reestablished during or
      shortly after therapy. All animals showed enrichment of transgenic granulocytes
      (range: 15- to 101-fold) and lymphocytes (range: 16- to 55-fold) in peripheral
      blood, bone marrow, and spleen. No significant differences were observed between
      individual treatment groups. Serial transplants demonstrated protection in
      secondary recipients and confirmed the transduction of transplantable stem cells.
      Thus, these data demonstrate efficient protection from hematotoxicity and
      substantial enrichment of transgenic cells following MGMT(P140K) gene transfer
      and treatment with different O(6)-alkylating drugs.

PMID- 12189524
TI  - Adenovirus-mediated in vivo B7-1 gene transfer induces anti-tumor immunity
      against pre-established primary tumor and pulmonary metastasis of rat
      osteosarcoma.
AB  - We have previously reported that an osteosarcoma vaccine generated by ex vivo
      transfection of B7-1 cDNA induces protective as well as curative immunity against
      B7-1-negative parental osteosarcoma. Because establishment of human osteosarcoma
      cell lines, which is a prerequisite for ex vivo gene transfer, is rarely
      successful, we, in the present study, investigated the therapeutic efficacy of
      adenovirus-mediated in vivo B7-1 gene transfer to pre-established primary tumor
      as well as pulmonary metastasis of osteosarcoma. Adenovirus-mediated rat B7-1
      gene transfer induced (a) expression of B7-1 molecules in osteosarcoma cells by
      both in vitro and in vivo infection procedures, (b) curative immunity against pre
      established primary osteosarcoma and, subsequently, hosts gained protection
      against additional challenge of parental B7-1-negative osteosarcoma cells, (c)
      systemic immunity against pre-established pulmonary metastasis, and (d)
      activation of regional lymph node CD4(+) T cells, expansion of dendritic cells
      and natural killer cells and the secretion of interferon-gamma. These findings
      collectively support the therapeutic value of adenovirus-mediated in vivo gene
      transfer on osteosarcoma, which is of greater simplicity than cell-based B7-1
      vaccine, and represent an attractive strategy for therapy of patients with
      metastatic osteosarcama who acquired resistance to current therapeutic protocols.

PMID- 12189525
TI  - Homing and survival of thymidine kinase-transduced human T cells in NOD/SCID
      mice.
AB  - The herpes simplex virus thymidine kinase (HSV-tk) gene conferring ganciclovir
      (GCV)-specific sensitivity to transduced cells might control Graft-versus
      Leukemia (GvL)/Graft-versus-Host Disease (GvHD). Human T lymphocytes were
      engineered with an LSN-tk retroviral vector encoding tk and neomycin resistance
      (NeoR) genes. A total of 80 x 10(6) tk(+) lymphocytes were injected
      intraperitoneally in NOD-SCID mice. Engraftment was evaluated by human
      CD45(+)/CD3(+) cytofluorimetric analysis and NeoR-based polymerase chain reaction
      (PCR) on peripheral blood, bone marrow, liver, thymus, and spleen on day +5.
      After 14 days, GCV (10 mg/kg daily) cytofluorimetric analysis and PCR were
      repeated (day +19). Immunohistological studies with anti-CD3 monoclonal antibody
      followed by alkaline phosphatase and monoclonal anti-alkaline phosphatase
      staining were performed on spleen and liver at the same time points. Human
      CD45(+)/CD3(+) cells were engrafted in all tissues on day +5 according to
      cytofluorimetry, immunohistology, and PCR. Lymphocytes "homed" to the white pulp
      T-cell area and to the red pulp; liver localization is prevalently at the
      periportal area. After GCV (day +19), cytofluorimetry and immunohistology showed
      very few CD3(+) cells. PCR identified the transgene in 22% tissue samples
      (positive only in thymus and spleen). GvHD did not occur in any animal. These
      data demonstrate elevated doses of human-transduced CD3(+) cells engraft in
      NOD/SCID mice; after GCV, very few CD3(+) cells can be detected and those that
      escape treatment can be found in the thymus and in the spleen on day +19. Lack of
      full response to GCV may account for cases of GvHD in patients receiving tk
      transduced T lymphocytes.

PMID- 12189526
TI  - Construction and production of oncotropic vectors, derived from MVM(p), that
      share reduced sequence homology with helper plasmids.
AB  - The production of currently available vectors derived from autonomous
      parvoviruses requires the expression of capsid proteins in trans, from helper
      sequences. Cotransfection of a helper plasmid always generates significant
      amounts of replication-competent virus (RCV) that can be reduced by the
      integration of helper sequences into a packaging cell line. Although stocks of
      minute virus of mice (MVM)-based vectors with no detectable RCV could be produced
      by transfection into packaging cells; the latter appear after one or two rounds
      of replication, precluding further amplification of the vector stock. Indeed,
      once RCVs become detectable, they are efficiently amplified and rapidly take over
      the culture. Theoretically RCV-free vector stocks could be produced if all
      homology between vector and helper DNA is eliminated, thus preventing homologous
      recombination. We constructed new vectors based on the structure of spontaneously
      occurring defective particles of MVM. Based on published observations related to
      the size of vectors and the sequence of the viral origin of replication, these
      vectors were modified by the insertion of foreign DNA sequences downstream of the
      transgene and by the introduction of a consensus NS-1 nick site near the origin
      of replication to optimize their production. In one of the vectors the inserted
      fragment of mouse genomic DNA had a synergistic effect with the modified origin
      of replication in increasing vector production.

PMID- 12189527
TI  - Electrotransfer of gene encoding endostatin into normal and neoplastic mouse
      tissues: inhibition of primary tumor growth and metastatic spread.
AB  - Electroporation-mediated gene transfer relies upon direct delivery of plasmids
      into cells permeabilized by electric fields, a method more efficient than
      transfer using nonviral vectors, although neither approaches the transfer
      efficiency of viral vectors. Here we studied electrotransfer of a gene encoding
      an angiogenesis inhibitor (endostatin) into primary tumors and muscle tissues,
      which would serve as a site of synthesis and secretion into the bloodstream of a
      therapeutic antimetastatic protein with systemic effects. Optimum electroporation
      conditions (voltage, number and duration of impulses, separation of caliper
      electrodes) were first established to maximize expression of a reporter gene
      transferred into murine Renca kidney carcinoma, B16(F10) melanoma, or skeletal
      muscle tissues. In neoplastic tissues, electrotransfer of plasmid DNA was far
      more efficient than electroporation with lipoplexes, but no differences between
      naked DNA and lipoplexes were found in case of electroporated muscles. We then
      studied the electrotransfer of plasmid DNA carrying the endostatin gene into pre
      established experimental Renca tumors. A significant inhibition of tumor growth
      was observed in animals electroporated with this construct. Electrotransfer of
      the endostatin gene into muscle tissues resulted in reduced numbers of
      experimental B16(F10) metastases in the lungs. This study clearly shows that
      electroporation may be used to efficiently transfer antiangiogenic genes into
      both normal and neoplastic tissues.

PMID- 12189528
TI  - Enhanced HER-2/neu-specific antitumor immunity by cotransduction of mouse
      dendritic cells with two genes encoding HER-2/neu and alpha tumor necrosis
      factor.
AB  - The present study uses an in vivo murine tumor model expressing the human HER
      2/neu antigen to evaluate the potential vaccine using dendritic cells (DCs)
      infected with adenovirus AdVHER-2. We first investigated whether infected DCs
      (DC(HER-2)) engineered to express HER-2/neu could induce HER-2/neu-specific
      immune responses. Our data showed that (i) AdVHER2-infected DC(HER-2) expressed
      HER-2/neu by Western blot and flow cytometric analysis, and (ii) vaccination of
      mice with DC(HER-2) induced HER-2/neu-specific cytotoxic T-lymphocyte (CTL)
      responses, but protected only 25% of vaccinated mice from challenge of 3 x 10(5)
      MCA26/HER-2 tumor cells. Further, to enhance the efficacy of DC(HER-2) vaccine,
      we coinfected DCs with both AdVHER-2 and AdVTNF-alpha. The infected DCs (DC(HER
      2/TNF-alpha)) displayed the expression of both HER-2/neu and TNF-alpha by flow
      cytometric and ELISA analysis. We next investigated whether DC(HER-2/TNF-alpha)
      could induce stronger HER-2/neu-specific immune responses. We found that DC(HER
      2/TNF-alpha) displayed up-regulation of immunologically important CD40, CD86, and
      ICAM-I molecules compared with DC(HER-2), indicating that the former ones are
      more mature forms of DCs. Vaccination of DC(HER-2/TNF-alpha) induced stronger
      allogeneic T-cell proliferation and 36% enhanced HER-2/neu-specific T-cell
      responses in vitro than DC(HER-2) cells. More importantly, it stimulated the
      significant anti-HER-2/neu immunity in vivo, which protected 8/8 mice from
      challenge of 3 x 10(5) MCA26/HER-2 tumor cells. Therefore, DCs genetically
      engineered to express both the tumor antigen and cytokines such as TNF-alpha as
      an immunoadjuvant are likely to represent a new direction in DC vaccine of
      cancer.

PMID- 12189529
TI  - Efficient genetic modification of murine dendritic cells by electroporation with
      mRNA.
AB  - Recently, human dendritic cells (DCs) pulsed with mRNA encoding a broad range of
      tumor antigens have proven to be potent activators of a primary anti-tumor
      specific T-cell response in vitro. The aim of this study was to improve the mRNA
      pulsing of murine DC. Compared to a standard lipofection protocol and passive
      pulsing, electroporation was, in our hands, the most efficient method. The
      optimal conditions to electroporate murine bone marrow-derived DCs with mRNA were
      determined using enhanced green fluorescent protein and a truncated form of the
      nerve growth factor receptor. We could obtain high transfection efficiencies
      around 70-80% with a mean fluorescence intensity of 100-200. A maximal expression
      level was reached 3 hours after electroporation. A clear dose-response effect was
      seen depending on the amount of mRNA used. Importantly, the electroporation
      process did not affect the viability nor the allostimulatory capacity or
      phenotype of the DC. To study the capacity of mRNA-electroporated DCs to present
      antigen in the context of MHC classes I and II, we made use of chimeric
      constructs of ovalbumin. The dose-dependent response effect and the duration of
      presentation were also determined. Together, these results demonstrate that mRNA
      electroporation is a useful method to generate genetically modified murine DC,
      which can be used for preclinical studies testing immunotherapeutic approaches.

PMID- 12189530
TI  - Synergistic cytotoxicity of buthionine sulfoximine (BSO) and intensive melphalan
      (L-PAM) for neuroblastoma cell lines established at relapse after myeloablative
      therapy.
AB  - Patients with high-risk neuroblastoma (NB) initially respond to aggressive,
      alkylator-based therapy only to die from recurrent disease that is refractory to
      chemotherapy, including alkylating agents. We examined the ability of buthionine
      sulfoximine (BSO)-mediated glutathione (GSH) depletion to modulate melphalan (L
      PAM) resistance in five NB cell lines established after progressive disease
      following myeloablative therapy (high-dose melphalan, carboplatin, etoposide and
      total body irradiation) supported by autologous hematopoietic stem cell
      transplant (AHSCT), and in 15 NB cell lines established at diagnosis or after non
      myeloablative therapy (pre-AHSCT). Four of five post-AHSCT NB cell lines and 10
      of 15 pre-AHSCT NB cell lines were sensitive to single agent BSO (LC(90) <300
      microM BSO), while two of five post-AHSCT lines and one of 15 pre-AHSCT lines
      showed high-level resistance to L-PAM (LC(90)>30 microM). Fixed ratio analysis
      demonstrated BSO/L-PAM synergy (combination index <1) for all five post-AHSCT and
      for all 15 pre-AHSCT cell lines tested. Multi-log cytotoxicity (often exceeding
      four logs of cell kill) was observed in post-AHSCT L-PAM-resistant cell lines
      (including p53 non-functional lines) only when clinically achievable
      concentrations of BSO were combined with myeloablative concentrations of L-PAM.
      We conclude that most neuroblastoma cell lines, including post-AHSCT NB cell
      lines that are highly resistant to myeloablative levels of L-PAM and lack p53
      function, are sensitive to clinically achievable concentrations of L-PAM and BSO.
      However, some L-PAM-resistant NB cell lines (especially those lacking p53
      function) require dose escalation of L-PAM to myeloablative concentrations in
      order to demonstrate significant synergistic cytotoxicity. Thus, optimal clinical
      application of BSO/L-PAM may require AHSCT.

PMID- 12189531
TI  - The effect of modulation of glutathione cellular content on busulphan-induced
      cytotoxicity on hematopoietic cells in vitro and in vivo.
AB  - Busulphan is used in conditioning regimens prior to SCT. A relationship between
      exposure to busulphan, expressed as an area under the plasma concentration time
      curve (AUC), and effect and/or adverse effects, such as veno-occlusive disease
      (VOD), was reported. Exhaustion of glutathione (GSH) contributes to VOD and
      modulation of intracellular levels of GSH influences bulsulphan-induced toxicity
      in hepatocytes. Thus, increase of GSH might serve as prophylaxis against VOD.
      However, it should not interfere with the myeloablative effects of busulphan. We
      investigated the relationship between exposure to busulphan, and its in vitro
      toxicity to CD34(+) hematopoietic progenitors from volunteers using clonogenic
      assays. Busulphan inhibited colony formation by CD34(+) cells in an AUC-dependent
      manner. Myeloid progenitors were more sensitive than erythroid progenitors,
      expressed as 100% inhibition of colony formation (68.7 +/- 7.5 microg.h/ml and
      140.3 +/- 35.7, respectively). The observed exposure corresponds to the total AUC
      obtained in patients treated with busulphan (1 mg/kg/day) for 4 days. Secondly,
      we studied the effect of modulation of GSH cellular levels on busulphan-induced
      toxicity in vitro in CD34(+) cells from volunteers, and in vivo in bone marrow
      cells from Balb/c mice. The intracellular concentration of GSH was increased or
      decreased by treatment with N-acetylcysteine or buthionine sulfoximine,
      respectively. Neither in vitro nor in vivo treatment with GSH modulators affected
      the hematological toxicity of busulphan. Thus, N-acetylcysteine would not
      interfere with the myeloablative effect of busulphan and therefore it is a
      potential candidate for VOD prophylaxis during busulphan-based conditioning
      regimens.

PMID- 12189532
TI  - Phase II trial of sequential high-dose chemotherapy with paclitaxel, melphalan
      and cyclophosphamide, thiotepa and carboplatin with peripheral blood progenitor
      support in women with responding metastatic breast cancer.
AB  - A single high-dose cycle of chemotherapy can produce response rates in excess of
      50%. However, disease-free survival (DFS) is 15-20% at 5 years. The single most
      important predictor of prolonged DFS is achieving a complete response (CR).
      Increasing the proportion of patients who achieve a complete response may improve
      disease-free survival. Women with metastatic breast cancer and at least a partial
      response (PR) to induction chemotherapy received three separate high-dose cycles
      of chemotherapy with peripheral blood progenitor support and G-CSF. The first
      intensification was paclitaxel (825 mg/m(2)), the second melphalan (180 mg/m(2))
      and the third consisted of cyclophosphamide 6000 mg/m(2) (1500 mg/m(2)/day x 4),
      thiotepa 500 mg/m(2) (125 mg/m(2)/day x 4) and carboplatin 800 mg/m(2) (200
      mg/m(2)/day x 4) (CTCb). Sixty-one women were enrolled and 60 completed all three
      cycles. Following the paclitaxel infusion most patients developed a reversible,
      predominantly sensory polyneuropathy. Of the 30 patients with measurable disease,
      12 converted to CR, nine converted to a PR*, and five had a further PR, giving an
      overall response rate of 87%. The toxic death rate was 5%. No patient progressed
      on study. Thirty percent are progression-free with a median follow-up of 31
      months (range 1-43 months) and overall survival is 61%. Three sequential high
      dose cycles of chemotherapy are feasible and resulted in a high response rate.
      The challenge continues to be maintenance of response and provides the
      opportunity to evaluate strategies for eliminating minimal residual disease.

PMID- 12189533
TI  - High-dose chemotherapy as salvage treatment for seminoma.
AB  - Between October 1989 and February 1997, 13 patients with refractory or relapsed
      seminomas were treated with high-dose chemotherapy (HDCT) as part of consecutive
      phase I/II studies. Six patients had failed prior cisplatin-based first-line
      treatments and seven patients had also failed cisplatin-based salvage treatments.
      After HDCT 4/12 (33%) patients became disease-free, 4/12 (33%) patients achieved
      partial remissions and 4/12 (33%) patients suffered progressive disease despite
      HDCT. One patient developed multiorgan failure and died. With a median follow-up
      of 4.5 years (range 3.4 to 8 years) five patients (38%) are alive and eight
      patients (62%) have died. Patients with non-pulmonary visceral metastases, with
      short relapse-free intervals and with cisplatin-refractory tumors were more
      likely to fail. HDCT can be curative in seminoma patients even if offered as
      second salvage treatment.

PMID- 12189534
TI  - Omission of day +11 methotrexate after allogeneic bone marrow transplantation is
      associated with increased risk of severe acute graft-versus-host disease.
AB  - The combination of CYA and short-course MTX is commonly used for GVHD prophylaxis
      after allogeneic BMT. Severe mucositis and organ dysfunction early after
      transplantation often lead to omission of the day +11 dose of MTX. To examine
      whether this omission increases the risk of acute or chronic GVHD, we reviewed
      135 allogeneic BMTs performed at our institution in which CYA and short-course
      MTX prophylaxis were used. Patients receiving less than three doses of MTX and
      those who died before day +11 were excluded. Of the 123 eligible patients, 84
      received all four doses and 39 received three doses, with the fourth dose
      withheld because of severe mucositis (n = 27) or hepatic or renal dysfunction (n
      = 12). Acute GVHD of any grade developed in 23 patients (59%) in the three-dose
      group compared with 57 patients (68%) in the four-dose group (P = 0.33). Chronic
      GVHD developed in 15 patients (38%) in the three-dose group compared with 31
      patients (37%) in the four-dose group (P = 0.87). There was no difference in the
      overall rate of acute or chronic GVHD between the groups. However, the three-dose
      group was more likely to develop grade III or IV acute GVHD (12 of 39 (31%) )
      compared with the four-dose group (12 of 84 (14%); P = 0.03). Relapse-free
      survival was similar for the two groups. We conclude that omitting day +11 MTX
      appears to increase the risk of severe acute GVHD.

PMID- 12189535
TI  - Busulfan concentration and graft rejection in pediatric patients undergoing
      hematopoietic stem cell transplantation.
AB  - We retrospectively analyzed the relationship between busulfan average steady
      state plasma concentration (C(SS)) and graft rejection in 53 children receiving
      busulfan/cyclophosphamide (BU/CY) preparative regimens prior to hematopoietic
      stem cell transplantation (HSCT). Patients received a total oral busulfan dose of
      11 to 28 mg/kg followed by a total cyclophosphamide dose of 120 to 335 mg/kg in
      preparation for allogeneic grafts (HLA-matched or HLA partially matched sibling,
      parent or unrelated donor). Graft rejection occurred in eight (15%) patients.
      Busulfan C(SS) (P = 0.0024) was the only statistically significant predictor of
      rejection on univariate logistic regression analysis, with the risk of rejection
      decreasing with an increase in busulfan C(SS). Severe (grade 3 or 4) regimen
      related toxicity (RRT) occurred in four patients. Ten patients (19%) had a
      busulfan C(SS) higher than 900 ng/ml, one of whom had severe RRT. Higher and
      variable doses of cyclophosphamide may explain the lack of a relationship between
      busulfan C(SS) and RRT in children. It may be possible to improve the outcome of
      HSCT in pediatric patients receiving the BU/CY regimen through optimization of
      busulfan C(SS) and better definition of the contribution of activated
      cyclophosphamide metabolites to toxicity.

PMID- 12189536
TI  - Nosocomial outbreak of Legionella pneumophila serogroup 3 pneumonia in a new bone
      marrow transplant unit: evaluation, treatment and control.
AB  - A nosocomial outbreak of pneumonia caused by Legionella pneumophila serogroup 3
      occurred in four patients following hematopoietic stem cell transplantation
      (HSCT) in a new bone marrow transplantation (BMT) unit during a 2 week period.
      The causative organism was recovered from the water supply system to the same
      unit just before the outbreak. Nineteen other BMT patients were hospitalized in
      the same unit at the same time, giving a frequency of proven infection of 4/23 =
      17%. Immediately after recognition of the outbreak, use of tap water was
      forbidden, humidifiers were disconnected, and ciprofloxacin prophylaxis was
      started for all patients in the unit, until decontamination of the water was
      achieved. No other cases were detected. In conclusion, contamination of the
      hospital water supply system with legionella carries a high risk for legionella
      pneumonia among BMT patients. Early recognition of the outbreak, immediate
      restrictions of water use, antibiotic prophylaxis for all non-infected patients,
      and water decontamination, successfully terminated the outbreak.

PMID- 12189537
TI  - Evaluation of the NucliSens CMV pp67 assay for detection and monitoring of human
      cytomegalovirus infection after allogeneic stem cell transplantation.
AB  - Preemptive treatment based on the sensitive detection of CMV-DNA has helped to
      reduce HCMV-related mortality after allogeneic stem cell transplantation (SCT).
      Detection of active viral replication might help to better predict HCMV disease.
      In this study, 33 recipients at risk for HCMV infection after allogeneic SCT were
      prospectively monitored 1x/week for active HCMV infection by NASBA, whole blood
      DNA-PCR and virus culture assays. Preemptive antiviral therapy was initiated
      after the second positive PCR result, while NASBA results were not considered for
      clinical decision-making. Overall, a high agreement between PCR and NASBA on a
      per sample (85.3%) and per patient (87.9%) level was demonstrated. HCMV DNA
      titers in the blood were found to be higher in PCR(+)/NASBA(+) compared to
      PCR(+)/NASBA(-) samples (P < 0.01). None of the NASBA-negative patients developed
      HCMV disease. Sixteen of 18 patients receiving PCR-based preemptive therapy were
      also found NASBA positive. There was no difference between the assays for the
      time to the first positive test result. However, the time to the first negative
      test result upon initiation of antiviral therapy was significantly shorter for
      the NASBA assay (P = 0.002), indicating a high positive predictive value to
      assess the efficacy of antiviral therapy. Three patients developed late-onset
      HCMV disease, all of whom were found to be PCR and NASBA positive. In conclusion,
      the data presented clearly demonstrate the value of patient monitoring using the
      NASBA assay to early diagnose active HCMV infection and to assess the efficacy of
      antiviral therapy in high risk patients after allogeneic SCT. A prospective
      comparison of PCR-based vs NASBA-based preemptive therapy is ongoing.

PMID- 12189538
TI  - Hepatitis B virus reactivation with clinical flare in allogeneic stem cell
      transplants with chronic graft-versus-host disease.
AB  - We conducted a retrospective study with the aim of identifying risk factors and
      clinical characteristics associated with HBV reactivation and clinical flare
      after allogeneic stem cell transplantation (aSCT). We reviewed the King Faisal
      Specialist Hospital and Research Center International Bone Marrow Transplant
      Registry database from January 1998 to June 2000. Complete serological screening
      for HBV was available in 128 of 131 patients transplanted during that period.
      Fifty-four (42%) had evidence of prior infection and recovery from HBV before
      transplant (hepatitis B core antibody positive, B surface antigen negative).
      Forty-two were evaluable for HBV reactivation and clinical flare. Six (14%)
      reactivated with clinical flare as documented by seroconversion and/or positive
      HBV DNA in the serum with biochemical hepatitis at 5.5, 18, 18, 19, 21 and 23
      months post-transplant. Five of fifteen patients with chronic graft-versus-host
      disease (cGVHD) reactivated with clinical flare in contrast to 1/27 without cGVHD
      (RR: 9.0, 95% CI: 1.2-70.1 P < 0.02). HBV reactivation with clinical flare
      occurred during immunosuppressive therapy tapering or withdrawal in all patients.
      In conclusion, hepatitis B core antibody positive allogeneic stem cell recipients
      with cGVHD are at significant risk of HBV reactivation with clinical flare.

PMID- 12189539
TI  - Successful allogeneic blood stem cell transplantation for aplastic anemia in a
      patient with renal insufficiency requiring dialysis.
AB  - A 27-year-old man with aplastic anemia and renal insufficiency requiring dialysis
      underwent allogeneic PBSCT. The preparative regimen consisted of melphalan, ATG
      and TLI. GVHD prophylaxis consisted of cyclosporine and prednisolone. He was
      dialyzed prior to administration of melphalan and at 24 and 72 h after it.
      Otherwise, the dialysis schedule was unchanged, at three times a week.
      Engraftment was rapid. Regimen-related toxicity was minimal. Pharmacokinetic
      parameters of melphalan were not significantly altered with its plasma half-life
      1.5 h. Patients with renal failure can receive allogeneic HSCT, and a combination
      of melphalan, ATG and TLI may serve as an alternative to CY and ATG.

PMID- 12189540
TI  - 'Alternative' cancer cures via the Internet?

PMID- 12189542
TI  - A multicentre phase II study of cisplatin and gemcitabine for malignant
      mesothelioma.
AB  - Our previous phase II study of cisplatin and gemcitabine in malignant
      mesothelioma showed a 47.6% (95% CI 26.2-69.0%) response rate with symptom
      improvement in responding patients. Here we confirm these findings in a
      multicentre setting, and assess the effect of this treatment on quality of life
      and pulmonary function. Fifty-three patients with pleural malignant mesothelioma
      received cisplatin 100 mg m(-2) i.v. day 1 and gemcitabine 1000 mg m(-2) i.v.
      days 1, 8, and 15 of a 28 day cycle for a maximum of six cycles. Quality of life
      and pulmonary function were assessed at each cycle. The best response achieved in
      52 assessable patients was: partial response, 17 (33%, 95% CI 20-46%); stable
      disease, 31 (60%); and progressive disease, four (8%). The median time to disease
      progression was 6.4 months, median survival from start of treatment 11.2 months,
      and median survival from diagnosis 17.3 months. Vital capacity and global quality
      of life remained stable in all patients and improved significantly in responding
      patients. Major toxicities were haematological, limiting the mean relative dose
      intensity of gemcitabine to 75%. This schedule of cisplatin and gemcitabine is
      active in malignant mesothelioma in a multicentre setting. Investigation of
      alternative scheduling is needed to decrease haematological toxicity and increase
      the relative dose intensity of gemcitabine whilst maintaining response rate and
      quality of life.

PMID- 12189541
TI  - The case for the introduction of new chemotherapy agents in the treatment of
      advanced non small cell lung cancer in the wake of the findings of The National
      Institute of Clinical Excellence (NICE).
AB  - After years of nihilism towards the use of chemotherapy for non small cell lung
      cancer in the UK it would appear that we have now reached the point where the use
      of chemotherapy to relieve symptoms, maintain quality of life, and prolong life,
      are now accepted for informed patients with good performance status willing to
      accept short-term toxicities. The use of the new agents vinorelbine, gemcitabine
      and paclitaxel in combination with cisplatin or carboplatin are all active
      regimens which offer small but real advantages over standard UK triple therapies
      (MVP, MIC) in terms of resource use, toxicity profiles and response rates.
      Overall survival could be increased by as much as 10% at one year on indirect
      comparisons. The use of docetaxel as second line therapy now offers lung cancer
      patients a second bite of the cherry, and should overall also prolong survival.
      It is only in embracing these small gains that we can currently make progress in
      the treatment of NSCLC.

PMID- 12189543
TI  - Weekly gemcitabine plus Epirubicin as effective chemotherapy for advanced
      pancreatic cancer: a multicenter phase II study.
AB  - The current role of chemotherapy in pancreatic carcinoma is limited, and progress
      in the treatment of this disease represents a significant challenge to medical
      oncology. The most promising drug under study is gemcitabine, a relatively new
      antimetabolite that represents an attractive candidate for combination
      chemotherapy because of its excellent side-effect profile and the absence of
      overlapping toxicities with other chemotherapeutic agents. Combined
      administration of gemcitabine and anthracyclines could result in the induction of
      DNA breaks that are not easily repaired by the cell's machinery, thus enhancing
      the apoptotic signals triggered by these lesions. Forty-four patients with
      locally advanced and/or metastatic pancreatic adenocarcinoma were enrolled in
      this multicenter study. Patients received Epirubicin 20 mg m(-2) for 3 weeks
      followed by 1 week of rest (1 cycle) and gemcitabine 1000 mg m(-2) after
      Epirubicin on the same day. All were assessable for toxicity and response, 11
      patients responded to treatment with one complete response and 10 partial
      responses, for an overall response rate of 25%. Median survival was 10.9 months
      (range, 2-26 months). Therapy was well tolerated, with a low incidence of
      haematologic grade >2 toxicity. A total of 12 of 27 (44.4%) eligible patients
      attained a clinical benefit response. Our findings suggest that the gemcitabine
      epirubicin schedule is active and well tolerated in patients with advanced
      pancreatic cancer.

PMID- 12189544
TI  - Tailoring communication in consultations with women from high risk breast cancer
      families.
AB  - This multicentre study examined the influence of patient demographic, disease
      status and psychological variables on clinical geneticists/genetic counsellors
      (consultants) behaviours in initial consultations with women from high-risk
      breast cancer families. One hundred and fifty-eight women completed a pre-clinic
      self-report questionnaire. The consultations were audiotaped, transcribed
      verbatim and coded. Consultants did not vary their behaviour according to women's
      expectations. However, significantly more aspects of genetic testing were
      discussed with women who were affected with breast cancer (P<0.001), screening
      and management with unaffected women (P=0.01) and breast cancer prevention with
      younger women (P=0.01). Prophylactic mastectomy was discussed more frequently
      with women with medical and allied health training (P=0.02), and prophylactic
      oophorectomy with women affected with breast cancer (P=0.03), those in non
      professional occupations (P=0.04) and with a family history of breast and ovarian
      cancer (P<0.001). Consultants used significantly more behaviours to facilitate
      understanding with women who were in non-professional occupations (P=0.04);
      facilitated active patient involvement more with women affected with breast
      cancer (P<0.001) and used more supportive and counselling behaviours with
      affected women (P=0.02). This study showed that patient demographics were more
      likely to predict consultants' communication behaviours than the woman's
      psychological status. Methods to facilitate assessment of psychological morbidity
      are needed to allow more tailored communication.

PMID- 12189545
TI  - Evidence of seasonality in the diagnosis of monocytic leukaemia.
AB  - Evidence of seasonality in the diagnosis of monocytic leukaemia in England and
      Wales is presented, with a maximum diagnosis rate in February/March and a minimum
      in August/September. Previous published results for monocytic leukaemia are of
      small sample size yet appear consistent with this finding.

PMID- 12189547
TI  - Space-time clustering analyses of childhood acute lymphoblastic leukaemia by
      immunophenotype.
AB  - Space-time clustering analyses of acute lymphoblastic leukaemia in children, by
      immunophenotype, were carried out using a population-based registry. Significant
      evidence was found of space-time clustering for cases of the precursor B-cell sub
      type, in the childhood peak, based on time and location at birth.

PMID- 12189546
TI  - Haemophilus influenzae type b vaccine formulation and risk of childhood
      leukaemia.
AB  - Incidence of childhood leukaemia was studied among subjects of a vaccine trial in
      Finland comparing the polysaccharide-diptheria toxoid conjugate and
      oligosaccharide-CRM197 conjugate Haemophilus influenzae type b conjugate vaccine
      formulations. Eighty cases of childhood leukaemia were detected: 35 among
      children on the polysaccharide-diptheria toxoid conjugate arm, and 45 among
      children on the oligosaccharide-CRM197 conjugate arm, which was not statistically
      significant.

PMID- 12189548
TI  - Cancer of the larynx in non-smoking alcohol drinkers and in non-drinking tobacco
      smokers.
AB  - The separate effect of alcohol and tobacco on laryngeal cancer was analysed in
      two case-control studies from Italy and Switzerland, comprising 40 non-smoking
      and 68 non-drinking cases, and 160 non-smoking and 161 non-drinking controls. The
      multivariate odds ratio was 2.46 for heavy drinkers non-smokers, and 9.38 for
      current smokers non-drinkers.

PMID- 12189549
TI  - Interaction between alcohol dehydrogenase II gene, alcohol consumption, and risk
      for breast cancer.
AB  - MaeIII Restriction Fragment Length Polymorphism in exon 3 of the alcohol
      dehydrogenase II was assessed in serum from 467 randomly selected German women
      and 278 women with invasive breast cancer to evaluate the interaction between a
      polymorphism of the alcohol dehydrogenase II gene, alcohol consumption and risk
      for breast cancer. In both groups, usual consumption of different alcoholic
      beverages was asked for using semiquantitative food frequency questionnaires. We
      used multivariable logistic regression to separately estimate the association
      between alcohol consumption and alcohol dehydrogenase II polymorphism in the
      population sample and women with breast cancer. The alcohol dehydrogenase II
      polymorphism was detected in 14 women from the population sample (3.0%) and in 27
      women with invasive breast cancer (9.7%). Frequency of alcohol consumption was
      independent of the genotype in the population sample. In women with breast
      cancer, there was a significant inverse association between the alcohol
      dehydrogenase II polymorphism and frequency of alcohol consumption (adjusted case
      only odds ratio over increasing frequency of alcohol consumption=0.5; P for
      interaction=0.02). We observed a gene-environment interaction between the alcohol
      dehydrogenase II polymorphism, alcohol consumption, and risk for breast cancer.
      Breast cancer risk associated with alcohol consumption may vary according to the
      alcohol dehydrogenase II polymorphism, probably due to differences in alcohol
      metabolism.

PMID- 12189550
TI  - Do parents of children with congenital malformations have a higher cancer risk? A
      nationwide study in Denmark.
AB  - To investigate whether parents of children with congenital malformations more
      often developed cancer after birth of the child, a population-based case-control
      study in Denmark was undertaken. By linking the Cancer Registry with the Central
      Population Registry, we identified 8783 cancer patients having their first child
      born between 1977 and 1995 before the cancer was diagnosed. Parents of 41 206
      firstborn children of a 10% random sample of newborns from the Birth Registry
      between 1980 and 1995 were identified as controls. We obtained malformation
      diagnoses of children of cases and controls by linking to the Hospital Discharge
      Registry. We estimated the association between malformation and cancer by using
      logistic regression, adjusting for maternal age at birth and sex of child. We
      found no increased risk of cancer in parents having children with malformations
      in general, but a higher cancer risk in parents of children born with cleft
      lip/palate, odds ratio (OR) for all cancer=1.8 (95% confidence interval 1.0-3.2),
      OR for lymphomas=4.2 (1.3-13.5) and OR for leukaemia=8.1 (2.0-33.7). This
      association was not restricted to cancer cases diagnosed shortly after birth of
      the child. Our results suggest a common genetic association between these
      diseases, but further studies are needed.

PMID- 12189551
TI  - Genetic polymorphisms of cytochrome P4501A1 and oesophageal squamous-cell
      carcinoma in Taiwan.
AB  - Several in vitro studies have demonstrated that genetic polymorphisms result in
      functionally significant changes in cytochrome p4501A1 (either CYP1A1 MspI or
      exon 7) but the few epidemiologic studies of these polymorphisms in oesophageal
      squamous-cell carcinoma have been inconclusive. These inconclusive results
      motivated us to further examine the relationship between CYP1A1 MspI and exon 7
      polymorphisms and risk of oesophageal cancer. In total, 146 cases of oesophageal
      squamous-cell-carcinoma and 324 control cases (a total of 470 cases) were
      genotyped from records at three Taiwan hospitals. No significant association was
      noted for the CYP1A1 MspI polymorphism variable between carcinoma and control
      cases. In contrast, the frequency of Ile/Ile, Ile/Val, and Val/Val in exon 7 was
      68 (46.6%), 62 (42.5%), and 16 (11.0%) in carcinoma cases and 179 (55.3%), 127
      (39.2%), and 18 (5.6%) in control cases, respectively. After factoring out other
      potential contributing factors, patients with Val/Val showed a 2.48 (95% CT=1.15
      5.34) greater risk of developing oesophageal cancer than those with Ile/Ile. A
      slightly (albeit not significantly) greater risk was identified in subjects with
      Ile/Val (OR=1.34; 95% CI=0.86-2.07). These findings suggest that an exon 7
      polymorphism, not a MspI polymorphism, in CYP1A1 may be pivotal in the
      development of oesophageal cancer.

PMID- 12189552
TI  - Metallothionein in human oesophagus, Barrett's epithelium and adenocarcinoma.
AB  - The potential of the metal-binding protein, metallothionein, in assessing the
      progression of normal oesophagus through Barrett's to adenocarcinoma was
      investigated. Metallothionein was quantitatively determined in resected tissues
      from patients undergoing oesophagectomy for high grade dysplasia/adenocarcinoma
      and in biopsies from patients with Barrett's syndrome. In 10 cancer patients,
      metallothionein concentrations in adenocarcinoma were not significantly different
      from normal oesophagus, although six had elevated metallothionein concentrations
      in the metaplastic tissue bordering the adenocarcinoma. In 17 out of 20 non
      cancer patients with Barrett's epithelium, metallothionein was significantly
      increased by 108% (P<0.004). There was no association between the metallothionein
      levels in Barrett's epithelium and the presence of inflammatory cells, metaplasia
      or dysplasia. Metallothionein is a marker of progression from normal to Barrett's
      epithelium but is not increased in oesophageal adenocarcinoma.

PMID- 12189553
TI  - A model for co-expression pattern analysis of genes implicated in angiogenesis
      and tumour cell invasion in cervical cancer.
AB  - To date, numerous genes have been identified which are involved in both tumour
      neovascularisation (angiogenesis) and tumour cell invasion, and most of them are
      also expressed to some extent under normal physiological conditions. However,
      little is known about how these genes co-express in these settings. This study
      was undertaken to quantitate mRNA levels in normal and malignant cervical tissues
      of nine selected genes (VEGF(121), VEGF(165), VEGF(189), VEGF-C, eIF-4E, b-FGF,
      TSP-2, MMP-2 and MMP-9) implicated in the above processes using real-time
      quantitative RT-PCR. In addition, the Spearman's rank correlation was used to
      determine their co-expression patterns. The transcript levels for the different
      VEGF-A splice variants (VEGF(121), VEGF(165), VEGF(189)) were at least 10-fold
      higher in the cancer cases, with the highest levels in the primary tumours
      demonstrating lympho-vascular space involvement. The lymphangiogenic factor VEGF
      C and MMP-9 were upregulated 130- and 80-fold respectively in cervical cancers.
      The highest levels of VEGF-C mRNA were found in the lymph-node positive group.
      The transcript levels for b-FGF were similar in normal cervical tissue and early
      stage cervical cancer, however, higher levels were found in the cervical cancers
      with advanced stage disease. Comparing gene transcript levels between recurrent
      and non-recurrent cervical cancer patients revealed significant differences
      (P=0.038) in transcript levels for the angiogenesis inhibitor TSP-2, with the
      highest levels in non-recurrent cases. Co-expression pattern analysis in normal
      cervical tissue revealed highly significant co-expressions (P<0.0001) between TSP
      2 and most other genes analysed (VEGF(121), VEGF(165), VEGF-C, b-FGF and MMP-2).
      In cervical cancer, TSP-2 appears only to be highly co-expressed with MMP-2
      (P<0.0001). In contrast to normal cervical tissue, we found a highly significant
      co-expression (P<0.0001) between MMP-9 and VEGF(189) in cervical cancer. The
      combined application of real-time quantitative RT-PCR and Spearman's rank
      correlation identifies gene transcripts which are simultaneously co-expressed.
      Our results revealed a significant co-expression between the angiogenesis
      inhibitor TSP-2 and most other genes analysed in normal cervical tissue. In
      cervical cancer, we found a strong upregulation of VEGF-C and MMP-9 mRNA, with a
      highly significant co-expression between MMP-9 and VEGF(189).

PMID- 12189554
TI  - Perinatal determinants of germ-cell testicular cancer in relation to histological
      subtypes.
AB  - We aimed to investigate the role of perinatal determinants on the risk for germ
      cell testicular cancer, with respect to the aetiological heterogeneity between
      seminomas and non-seminomas. A case-control study of 628 case patients with
      testicular cancer (308 seminomas and 320 non-seminomas) and 2309 individually
      matched controls was nested within a cohort of boys born from 1920 to 1980 in two
      Swedish regions (Uppsala-Orebro Health Care Region and Stockholm). Cases were
      diagnosed from 1958 to 1998 and were identified through the Swedish National
      Cancer Registry. Perinatal information on cases and controls was collected
      through charts available at maternity wards. Gestational duration, categorised in
      three categories (<37, 37-41, >41 weeks), was negatively associated with the risk
      for testicular cancer (P value for linear trend=0.008). A protective effect of
      long gestational duration and an increased risk for high birth weight were found
      for seminomas. Non-seminomas were associated with short gestational duration,
      particularly among those with low birth order (odds ratio: 3.02, 95% confidence
      intervals: 1.53-5.97) and high maternal age (odds ratio: 2.33, 95% confidence
      intervals: 1.19-4.55). No significant differences were found in tests for
      heterogeneity between the two histological groups. Our data support the
      hypothesis that intrauterine environment affects the risk for germ-cell
      testicular cancer. Seminomas and non-seminomas seemed to have similar risk
      patterns, although they are not entirely congruent.

PMID- 12189555
TI  - Differential diagnosis between chronic pancreatitis and pancreatic cancer: value
      of the detection of KRAS2 mutations in circulating DNA.
AB  - KRAS2 mutations in codon 12 have been detected in about 80% of pancreatic
      cancers. The aim of this study was to evaluate the value of KRAS2 mutations
      detection in circulating deoxyribo nucleic acid to differentiate pancreatic
      cancer from chronic pancreatitis. Circulating deoxyribonucleic acid was isolated
      from serum in 47 patients with histologically proven pancreatic adenocarcinomas
      (26 males, median age 65 years) and 31 controls with chronic pancreatitis (26
      males, median age 48 years). Mutations at codon 12 of KRAS2 gene were searched
      for using polymerase chain reaction and allele specific amplification. Serum
      carbohydrate antigen 19.9 levels were also determined. KRAS2 mutations were found
      in 22 patients (47%) with pancreatic cancer and in four controls with chronic
      pancreatitis (13%) (P<0.002). None of the latter developed a pancreatic cancer
      within the 36 months of median follow-up. The sensitivity, specificity, positive
      and negative predictive values of serum serum KRAS2 mutations for the diagnosis
      of pancreatic cancer were 47, 87, 85 and 52%, respectively. KRAS2 mutations were
      not related to age, gender, smoking habit, tumour stage, or survival. Among the
      26 patients with normal or non-contributive (due to cholestasis) serum
      carbohydrate antigen 19.9 levels, 14 (54%) had KRAS2 mutations. The combination
      of KRAS2 and carbohydrate antigen 19.9 gave a sensitivity, specificity, positive
      and negative predictive values for the diagnosis of pancreatic cancer of 98, 77,
      87 and 96%, respectively. Detection of KRAS2 mutations in circulating deoxyribo
      nucleic acid has a low sensitivity but a specificity about 90% for the diagnosis
      of pancreatic cancer. It seems particularly useful when serum carbohydrate
      antigen 19.9 levels are normal or inconclusive. A combined normal serum
      carbohydrate antigen 19.9 and absence of circulating KRAS2 mutations makes the
      diagnosis of pancreatic cancer extremely unlikely.

PMID- 12189557
TI  - Identical chemotherapy schedules given on and off trial protocol in small cell
      lung cancer: response and survival results.
AB  - Patients who are treated within clinical trials may have a survival benefit
      dependent on being a trial participant. A number of factors may produce such
      beneficial outcome including more rigorous adherence to a peer reviewed trial
      protocol, management by an experienced treatment team, being treated in a
      specialist centre etc. The current investigation compared patients treated on and
      off trial with the same standard arm treatment regimen. The results could then be
      interpreted without the confounding factors of differing treatment regimens,
      treatment teams or treatment hospitals. The results demonstrated given these
      circumstances that survival was no different for patients participating in a
      randomised trial compared with a group of patients similarly treated who were not
      eligible for trial entry or who declined randomisation. These results were
      obtained by the rigorous adherence to a defined protocol with the invaluable
      assistance of designated lung cancer staff.

PMID- 12189556
TI  - Retinoids cause apoptosis in pancreatic cancer cells via activation of RAR-gamma
      and altered expression of Bcl-2/Bax.
AB  - All-trans-retinoic acid and 9-cis-retinoic acid have been reported to have
      inhibitory effects on pancreatic adenocarcinoma cells and we have shown that this
      is partly due to induction of apoptosis. In this study, the mechanisms whereby 9
      cis-retinoic acid induces apoptosis in these cells were investigated. An
      involvement of the Bcl-2 family of proteins was shown, such that 9-cis-retinoic
      acid causes a decrease in the Bcl-2/Bax ratio. Overexpression of Bcl-2 also
      resulted in inhibition of apoptosis induced by 9-cis-retinoic acid. Furthermore,
      two broad-range caspase inhibitors blocked DNA fragmentation induced by 9-cis
      retinoic acid, but had no effect on viability defined by mitochondrial activity.
      Using synthetic retinoids, which bind selectively to specific retinoic acid
      receptor subtypes, we further established that activation of retinoic acid
      receptor-gamma is essential for induction of apoptosis. Only pan-retinoic acid
      receptor and retinoic acid receptor-gamma selective agonists reduced viability
      and a cell line expressing very low levels of retinoic acid receptor-gamma is
      resistant to the effects of 9-cis-retinoic acid. A retinoic acid receptor
      beta/gamma selective antagonist also suppressed the cytotoxic effects of 9-cis
      retinoic acid in a dose-dependent manner. This study provides important insight
      into the mechanisms involved in suppression of pancreatic tumour cell growth by
      retinoids. Our results encourage further work evaluating the clinical use of
      receptor subtype selective retinoids in pancreatic carcinoma.

PMID- 12189559
TI  - COX-2 selective inhibition reverses the trophic properties of gastrin in
      colorectal cancer.
AB  - Gastrin is a gastrointestinal peptide that possesses potent trophic properties on
      both normal and neoplastic cells of gastrointestinal origin. Previous studies
      have indicated that chronic hypergastrinaemia increases the risk of colorectal
      cancer and cancer growth and that interruption of the effects of gastrin could be
      a potential target in the treatment of colorectal cancer. Here we demonstrate
      that gastrin leads to a dose-dependent increase in colon cancer cell
      proliferation and tumour growth in vitro and in vivo, and that this increment is
      progressively reversed by pretreatment with the cyclo-oxygenase-2 inhibitor NS
      398. Gastrin was able to induce cyclo-oxygenase-2 protein expression, as well as
      the synthesis of prostaglandin E2, the major product of cyclo-oxygenase.
      Moreover, gastrin leads to approximately a two-fold induction of cyclo-oxygenase
      2 promoter activity in transiently transfected cells. The results of these
      studies demonstrate that cyclo-oxygenase-2 appears to represent one of the
      downstream targets of gastrin and that selective cyclo-oxygenase-2 inhibition is
      capable of reversing the trophic properties of gastrin and presumably might
      prevent the growth of colorectal cancer induced by hypergastrinaemia.

PMID- 12189558
TI  - Potential role of endocrine gastrin in the colonic adenoma carcinoma sequence.
AB  - The role of hyper-gastrinaemia in the incidence of colonic cancer remains to be
      clarified. The aim of this study was to determine whether cholecystokinin-2 (CCK
      2) receptor expression predicts the sensitivity of human colonic adenomas to the
      proliferative effects of serum hyper-gastrinaemia. Gene expression of the
      classical (74 kDa) CCK-2 receptor in human colonic adenoma specimens and cell
      lines, was quantified by real-time PCR. Western blotting, using a CCK-2 receptor
      antiserum, confirmed protein expression. A transformed human colonic adenoma was
      grown in SCID mice, with hyper-gastrinaemia induced by proton pump inhibitors.
      CCK-2 receptor blockade was achieved by using neutralising antiserum. Both human
      colonic adenoma cell lines and biopsies expressed CCK-2 receptor mRNA at levels
      comparable with CCK-2 receptor transfected fibroblasts and oxyntic mucosa.
      Western blotting confirmed immunoreactive CCK-2 receptor bands localised to 45,
      74 and 82.5 kDa. Omeprazole and lansoprazole-induced hyper-gastrinaemia
      (resulting in serum gastrin levels of 34.0 and 153.0 pM, respectively)
      significantly increased the weight of the human adenoma grafts (43% (P=0.016) and
      70% (P=0.014), respectively). The effect of hypergastrinaemia on tumour growth
      was reversed by use of antiserum directed against the CCK-2 receptor. Hyper
      gastrinaemia may promote proliferation of human colonic adenomas that express CCK
      2 receptor isoforms.

PMID- 12189561
TI  - Seeing the good and bad in aplastic anemia: is autoimmunity in AA dysregulated or
      antineoplastic?
AB  - Aplastic anemia (AA) is considered to be an autoimmune disease directed against
      hematopoietic stem cells (HSC), though knowledge on the inciting autoantigen(s)
      is scant. According to the traditional concept of autoimmunity the target tissue
      in autoimmune disease is essentially normal, and misdirected self-attack is
      caused by disturbed self-recognition. Recently, this theory has been challenged
      by the hypothesis that autoimmunity against solid tissues is directed against
      intrinsically abnormal, transforming cells, i.e. autoimmune reactions are
      essentially antineoplastic, attempting to eliminate cells signalling 'danger'.
      This theory might apply to AA as well. Observations such as the dysplastic traits
      typical of non-severe AA, the high prevalence of one or several abnormal
      hematopoietic clones and their resistance to apoptosis in newly diagnosed AA
      patients suggest that these cell populations do not develop secondarily, but
      expand primarily und could be the primary target of AA, normal hematopoietic stem
      cells being destroyed as innocent bystanders. If bone marrow hypoplasia/aplasia
      indeed reflects an immune reaction incited by outgrowth of transformed cells,
      immunosuppressive treatment of AA would have to be reconsidered, since a two
      edged sword. As a consequence, AA patients with a hyperreactive immune system may
      require more intense immunosuppressive therapy (IS), whereas patients with an
      anergic immune system may fare better with IS of lower intensity than the
      currently recommended standard.

PMID- 12189562
TI  - The homozygous state of Hb J Sardegna.
AB  - Hb J Sardegna is a well known innocent Hb variant which is widespread in
      Sardinia. As yet, homozygosity for Hb J Sardegna has not been documented. This
      report deals with the homozygous state for Hb J which we demonstrate by molecular
      analysis in two Sardinian siblings in which beta-thalassemia coexists. The Hb J
      specific mutation was determined both by enzyme digestion and by sequencing
      specific segments of PCR amplified alpha-globin genes. A pregnant girl showed
      mild non-sideropenic microcytic anemia, normal Hb A(2) levels (2.4%) on DE-52
      microchromatography, 50% of Hb variant on HPLC and 2.1 alpha/beta globin chain
      biosynthetic ratio. She proved to be a carrier of the beta degrees 6(-A)
      thalassemia determinant. The alpha-globin gene mapping did not reveal alpha
      thalassemia. Btg I restriction analysis of both alpha(2)-globin genes showed a
      recognition site defect for this enzyme in both chromosomes, which resulted to be
      the C-->A point mutation in homozygosity at the first nt of alpha(2)-globin gene
      50th codon by sequencing. This defect, typical of Hb J Sardegna, was also present
      in her brother. From a practical point of view, this study demonstrates that the
      association of beta-thalassemia with Hb J, may show falsely reduced Hb A(2)
      levels on routine Hb A(2) quantitation techniques, such as DE-52
      microchromatography. This possibility implies that identification methods such as
      simple Hb electrophoresis, which permit visualization of Hb A(J)(2) should be
      used in thalassemia screening involving populations in which Hb J and beta
      thalassemia coexist.

PMID- 12189560
TI  - Effect of a tumour-derived lipid-mobilising factor on glucose and lipid
      metabolism in vivo.
AB  - Treatment of ex-breeder male NMRI mice with lipid mobilising factor isolated from
      the urine of cachectic cancer patients, caused a significant increase in glucose
      oxidation to CO2 compared with control mice receiving phosphate buffered saline.
      Glucose utilisation by various tissues was determined by the 2-deoxyglucose
      tracer technique and shown to be elevated in brain, heart, brown adipose tissue
      and gastrocnemius muscle. The tissue glucose metabolic rate was increased almost
      three-fold in brain, accounting for the ability of lipid mobilising factor to
      decrease blood glucose levels. Lipid mobilising factor also increased overall
      lipid oxidation, as determined by the production of 14CO2 from [14C carboxy]
      triolein, being 67% greater than phosphate buffered saline controls over a 24 h
      period. There was a significant increase in [14C] lipid accumulation in plasma,
      liver and white and brown adipose tissue after administration of lipid mobilising
      factor. These results suggest that changes in carbohydrate metabolism and loss of
      adipose tissue, together with an increased whole body fatty acid oxidation in
      cachectic cancer patients, may arise from tumour production of lipid mobilising
      factor.

PMID- 12189563
TI  - Radiation therapy in early stage Hodgkin's disease: long-term results and adverse
      effects.
AB  - INTRODUCTION: Radiation therapy (RT) was the first treatment modality
      demonstrating cure of Hodgkin's disease. Long-term side-effects of this
      treatment, however, have become evident in the past few years. PATIENTS AND
      METHODS: By reviewing the results of megavoltage radiotherapy as initial
      treatment in a consecutive series of 106 patients with early-stage Hodgkin's
      disease (HD), survival, relapse-free interval, salvage rate of relapsing cases,
      and incidence of second tumours were evaluated. RESULTS: Subtotal node
      irradiation was given to all patients with supradiaphragmatic disease, except for
      15 patients with limited stage IA-IIA, who received mantle field treatment only.
      Inverted Y field irradiation was given to all seven patients with
      subdiaphragmatic disease. The median age was 32 years (range 14-77). The median
      follow-up was 140 months. The relapse-free interval of the patient population was
      78% at 5 years and 72% at 10 years. The overall survival (OS) was 90% and 79%,
      respectively. Salvage therapy was successful in 26 of 30 relapsing patients.
      Twelve recurrences were located inside the treatment field. Sixteen patients
      (15%) developed second malignancies: cancer of the lung (two), ovary (two),
      cervix (one), colon (two), breast (three), stomach (one), skin (two), hypopharynx
      (one), and non-Hodgkin lymphoma (two). Eleven of these were located within the
      radiation field. CONCLUSION: Although RT is intended to be a curative treatment,
      up to 30% recurrences occur. Mortality was not determined by primary HD, but by
      second malignancies, which are likely related to treatment. New treatment
      strategies, aiming at long-term freedom from relapse without carcinogenic side
      effects, are urgently needed.

PMID- 12189564
TI  - Thalidomide in patients with advanced multiple myeloma: a study of 83 patients-
      report of the Intergroupe Francophone du Myelome (IFM).
AB  - BACKGROUND: To evaluate treatment by thalidomide and identify predictive factors
      of survival, event free survival and response among patients with advanced
      multiple myeloma treated with thalidomide as single agent therapy. PATIENTS AND
      TREATMENT: Patients with advanced multiple myeloma (n=83) were treated with an
      oral dose of thalidomide (median 400 mg/day). At start of treatment, all patients
      had active disease and 58 (69%) had received at least one autologous
      transplantation. RESULTS: With a median follow-up of 338 days (range, 247-629
      days), 52 patients are alive, whereas 31 died between 8 and 150 days after the
      first administration of thalidomide. The response to thalidomide was considered
      as major in 11 patients (13%), partial in 29 patients (35%) and minor in 15
      patients (18%), giving a total response rate of 66% (54 out of 83 patients).
      Thirteen patients had stable disease and 15 patients progressed. In multivariable
      analysis, age greater than 60 years, short interval between diagnosis and onset
      of thalidomide, requirement for red blood cell transfusion, IgA isotype,
      platelets' count <80 x 10(9)/l and serum albumin level <30 g/l at the start of
      thalidomide were associated with poor outcome. These three last factors produced
      a simplified prognostic model for patients with advanced myeloma and treated with
      thalidomide. Thus, among the 38 patients without any of these unfavorable risk
      features, one-year overall survival and event free survival were 87% and 78%. By
      contrast, the 43 patients with at least one unfavorable feature had one-year
      overall survival and event free survival of 40% and 32%, respectively (Log-Rank,
      P=0.0002 for both). Patients who received > or =34.4 g of thalidomide in the
      first 90 days of treatment had a better outcome than those who received <34.4 g.
      However, the mean received daily dose of thalidomide in the first 90 days has not
      been found to influence survival, event free survival or response. Short-term
      side effects of thalidomide were generally moderate. CONCLUSION: Thalidomide is
      an effective treatment for patients with advanced myeloma, in particular, who
      have no poor-risk features. The poor results achieved by the other patients
      emphasize the need for prospective protocols using thalidomide in combination,
      especially with dexamethasone. In addition, further studies are needed to
      determine the optimal thalidomide dose and duration.

PMID- 12189565
TI  - Prolonged administration of all-trans retinoic acid in combination with intensive
      chemotherapy and G-CSF for adult acute myelogenous leukemia: single-centre pilot
      study in different risk groups.
AB  - INTRODUCTION: An exploratory trial was conducted to evaluate toxicity and
      potential therapeutic role of all trans-retinoic acid (ATRA) given long-term
      together with chemotherapy and G-CSF to adult patients with acute myelogenous
      leukemia (AML). MATERIALS AND METHODS: ATRA was administered orally at 45
      mg/m(2)/day on days 1-14 and 25 mg/m(2)/day on days 15-28 of two standard cycles
      (idarubicin, etoposide, cytarabine, G-CSF) and of up to three high-dose courses
      (cytarabine, G-CSF). The results obtained in 19 patients enrolled in the ATRA
      trial were compared with those from 29 comparable cases treated with the same
      schedule without ATRA, according to patient risk class and an in vitro study.
      RESULTS: ATRA was administered for a median of 52 days to the patients selected
      for study who achieved a remission. ATRA-related toxicity was mostly non-severe
      apart from high incidence of headache in conjunction with high-dose cytarabine.
      Complete remission (CR) rate after cycle 1 (54%), kinetics of hematological
      recovery, postremission treatment realization, disease-free survival (DFS 37.5%
      at three years) and overall survival (30% at three years) were not different
      between ATRA-treated and untreated patients. The only significant prognostic
      factor was the patient risk class, as defined by cytogenetics and other clinical
      criteria: DFS rate was 57% at three years in standard-risk cases compared to only
      19% in the high-risk group, with no influx by ATRA in either category. The in
      vitro study, in patients with a definite clinical response, failed to document
      any inhibitory or pro-apoptotic effect of ATRA on AML blast cells. CONCLUSION: As
      a consequence to these results, the pilot ATRA phase was closed. This study does
      not suggest a significant role for the present ATRA schedule as an adjunct to
      standard antileukemic therapy in adult AML.

PMID- 12189566
TI  - Inhibition of telomerase activity with hTERT antisense increases the effect of
      CDDP-induced apoptosis in myeloid leukemia.
AB  - INTRODUCTION: As reported previously, inhibition of telomerase activity with
      hTERT (human telomerase reverse transcriptase) mRNA AS PS-ODN (Antisense
      phosphorothioate oligodeoxynucleotide) could increase the effect for CDDP (cis
      diamminedichloroplatinum, CDDP) to induce apoptosis of HL-60 and K562 leukemic
      cells. In these studies, this phenomenon will be further investigated and
      expanded to leukemia cells from acute and chronic myeloid leukemia (AML and CML).
      MATERIALS AND METHODS: Cell samples of AML and CML patients, from the first
      affiliated hospital of Jinan University Medical College, were obtained. The
      primary cell culture was established to investigate whether or not the inhibition
      of telomerase activity with hTERT mRNA AS PS-ODN increased the effect for
      cisplatin to induce apoptosis of leukemic cells from patients. Cell growth was
      observed with trypan blue dye exclusion. hTERT protein was determined by tissue
      chemistry and flowcytometry. Telomerase activity was tested with the telomerase
      PCR ELISA assay kit (Boehringer Mannheim). RESULTS: The inhibition of telomerase
      activity with hTERT mRNA AS PS-ODN could significantly increase the
      susceptibility of AML or CML cells to CDDP. The apoptotic percentage of cells
      (AML: 42.68%; CML: 35.72%) treated with AS PS-ODN/CDDP was significantly
      different from that of cells (AML, 29.02%; CML, 23.84%) treated with S PS
      ODN/CDDP or CDDP. CONCLUSION: The inhibition of telomerase activity with hTERT
      mRNA AS PS-ODN could increase the effect for CDDP to induce apoptosis of leukemic
      cells from AML and CML patients.

PMID- 12189567
TI  - Interleukin-10 inhibits in vitro hematopoietic suppression and production of
      interferon-gamma and tumor necrosis factor-alpha by peripheral blood mononuclear
      cells from patients with aplastic anemia.
AB  - INTRODUCTION: Mononuclear cells (MNC) from patients with aplastic anemia (AA) can
      inhibit hematopoietic colony formation from normal bone marrow (BM) cells.
      Interferon-gamma (IFN-gamma) and tumor necrosis factor-alpha (TNF-alpha) are
      considered as soluble mediators of BM suppression in AA. Because of its cytokine
      synthesis inhibiting action, interleukin-10 (IL-10) could be a potentially useful
      molecule to modulate the hematopoietic effects of MNC from patients with AA.
      METHODS: Using coculture experiments we studied the effect of recombinant human
      IL-10 (rhIL-10) on the in vitro hematopoietic suppression by peripheral blood
      (PB) MNC from AA patients. RESULTS: PBMNC (5 x 10(5)/ml) from seven patients with
      AA caused a 40-100% reduction of normal burst-forming unit-erythroid (BFU-E)
      growth and a 38-91% reduction of colony-forming unit-granulocyte/macrophage (CFU
      GM) growth, respectively, in semisolid cocultures. IL-10 was highly effective in
      reversing growth inhibition in these cocultures. Addition of 10 ng/ml IL-10 to
      cocultures significantly restored growth of BFU-E in all seven cases and growth
      of CFU-GM in five of seven cases, respectively. The effect was dose dependent and
      correlated with decreased IFN-gamma and TNF-alpha production in suspension
      cultures. Using intracellular cytokine staining it was found that increased TNF
      alpha production in AA cells was derived from both CD4+ and CD8+ cells, whereas
      aberrant IFN-gamma synthesis was only detected in CD8+ cells. CONCLUSION: IL-10
      is effective in reversing in vitro hematopoietic suppression by PBMNC from AA
      patients. These results suggest therapeutic evaluation of rhIL-10 in patients
      with AA.

PMID- 12189569
TI  - Immune reconstitution during intensive chemotherapy in patients with human
      immunodeficiency virus related non-Hodgkin lymphoma.

PMID- 12189568
TI  - Steady-state platelet count and complications of sickle cell disease.

PMID- 12189570
TI  - [Influence of interaural time- and level differences on the binaural interaction
      components in normal adults].
AB  - BACKGROUND: Binaural interaction components of auditory brainstem responses have
      long been studied and its beta-wave has been shown to be correlated with
      directional hearing ability. As patients with auditory processing disorders such
      as patients with some sorts of learning disabilities frequently have difficulties
      with binaural processing it seems sensible to use binaural interaction components
      in the diagnosis of these disorders. METHODS: In order to obtain normal values
      and to investigate the influence of interaural time (ITD) and level differences
      (ILD) binaural interaction components were measured in 21 adults. Interaural time
      differences varied between 0 and 1.2 ms and interaural level differences between
      0 and 30 dB. RESULTS: beta-latencies increased significantly as interaural time
      differences increased while beta-amplitudes did not change significantly. In
      measurements with higher interaural time differences detection of the beta-wave
      was only rarely possible. The effect of interaural level differences on beta
      latencies was less pronounced and not significant as well as the influence of
      interaural level differences on beta-amplitudes. CONCLUSIONS: In the present
      study it could be shown that the beta-wave of the binaural interaction waveform
      is present in almost every normal hearing subject. As amplitudes show a
      considerable variation beta-latencies seem to be of higher diagnostic value than
      amplitudes.

PMID- 12189571
TI  - [Might the cooperation with neuropediatricians improve the treatment of hearing
      impaired children: retrospective analysis of a small group of children with
      hearing aids].
AB  - QUESTION: Present analysis was performed to test the hypothesis, that cooperation
      with neuropediatricians might improve the treatment of hearing impaired children.
      STUDY-DESIGN: In a retrospective study 31 children (21 females, 10 males) with
      impaired sensorineural hearing (27 binaural, 4 monaural) and hearing aids were
      analyzed: - 12 children with profound and severe hearing loss (HL), median
      diagnostic age (mda): 8 months; - 15 children with moderate and mild HL, mda: 58
      months and - 4 children with monaural HL, mda: 29 months. Neuropediatric
      examination included physical examination as well as psychometric testing.
      RESULTS: 1. Despite various medical efforts hearing impaired children are
      diagnosed very late in Germany. 2. About 65 % of the children exhibited
      neurodevelopmental deficits; about 25 % showed profound disabilities: 7 children
      with an IQ < 80, 1 child with ADHD (Attention Deficit Hyperactivity Disease) and
      1 child with cerebral seizures. Analysis indicates that especially in children
      with developmental disabilities and only mild/ moderate hearing impairment the
      risk for additional neuropediatric diseases is increased. CONCLUSION: In the
      present study a high portion of hearing impaired children exhibited additional
      neuropediatric diseases. Thus the regular cooperation with a neuropediatrician
      might be helpful for diagnosis and further treatment. The risk for additional
      neuropediatric disabilities might be enhanced especially in those children, which
      have been diagnosed late or in cases with mild/moderate hearing impairment and
      profound developmental disabilities.

PMID- 12189572
TI  - [Chromosome 5q-syndrome-ENT pathologies].
AB  - INTRODUCTION: The interstitial deletion of chromosome 5q is a disease of rare
      incidence, which might be hereditary or caused by spontaneous changes within the
      chromosome respectively. The pathology is based on the loss of chromosomal
      material within the long arm of chromosome 5. Clinical manifestations are mainly
      known in hematology, particular such as malignancies or hematopoetic
      malformation. Other morphological characteristics that have been described
      following deletion of chromosome 5q are deformity of the skull and the joints as
      well as heart defects. In the following we will present some pathologic findings
      focussing on the head and neck. PATIENT: We introduce a young female patient of 8
      months with deletion of the long arm of chromosome 5q. In addition to the known
      skeletal and hematopoetic disorders we discovered a unilateral deafness and a
      contralateral middle-graded combined hearing-loss as well as laryngomalacia.
      CONCLUSION: Infants with chromosome 5 syndrome should undergo an
      otorhinolaryngological examination to investigate anatomic malformations. In
      particular a brainstem electric response audiometry should be considered for
      early diagnosis and treatment of a possible hearing-loss. This ensures adequate
      and early support of the patients physical and psychological development.

PMID- 12189573
TI  - [Adenosquamous carcinoma of the palate].
AB  - A rare case of adenosquamous carcinoma in a 74 year-old man is reported.
      Presenting as a nodule on the soft palate, diagnosis was prolonged because of the
      benign macroscopic aspect. CT-scan and MR-tomography showed an encapsulated
      lesion but biopsy and histologic examination revealed the typical features of
      adenosquamous carcinoma. The tumour consisted of adenocarcinoma and squamous cell
      carcinoma in close proximity to minor salivary glands of which the tumour seemed
      to have its origin. This entity, although rare in the head and neck region has
      been documented to be very aggressive with early regional and hematogenic
      metastasis. Therefore it has to be distinguished from other tumours, especially
      from mucoepidermoid carcinomas of the salivary glands, which have a better
      prognosis. Adenosquamous carcinoma is considered to have poor radiosensitivity
      and chemotherapeutic approaches have also not been successful in the literature.
      In our case radical surgical therapy was performed by excision of the whole soft
      palate and bilateral neck dissection. This resulted in total removal of the
      tumour but revealed bilateral lymph node metastases. Vital functions were saved
      by reconstruction of the palate with a free vascularized tensor-fasciae-latae
      perforator-flap. For the first time in a case of adenosquamous carcinoma
      carcinoembryonic antigen in serum was monitored. A pretherapeutical 29-fold
      elevation resulted in a marked decrease after surgery, but supranormal values
      indicated remaining tumour burden which was found in metastases in the lung.
      Because of the limitations in therapy, early histologic diagnosis is most
      important in this highly malignant tumour.

PMID- 12189574
TI  - [Occupational exposure and cancer of the oral cavity and pharynx].
AB  - BACKGROUND: Occupational risk factors for the development of laryngeal cancer are
      well accepted, whereas the etiologic relationship between occupational exposure
      to various noxious influences and the development of cancer of the oral cavity
      and pharynx remain a matter of debate. Based on published data, occupational risk
      factors for cancer of the oral cavity and pharynx should be evaluated. METHODS:
      Publications since 1990 listed in the National Library of Medicine, textbooks and
      data obtained from the German Employer's Liability Insurance Association were
      evaluated. RESULTS: In several tobacco- and alcohol-adjusted case-control and
      cohort studies, an association with occupation in construction and metalworking
      industries, as painters, carpenters and machine operators was consistently found.
      The relative risks or standardized mortality rates ranged between 1.5 and 3. Some
      recent investigations found an association for workers in the paper and rubber
      industry. The results in regard to the textile and woodworking industry were
      inconclusive. CONCLUSION: In cases with moderate isolated tobacco or moderate
      isolated alcohol consumption, the risk attributable to occupational factors and
      smoking or drinking are of similar magnitude. According to German jurisdiction, a
      partial compensation of the acquired disability is then justified. In pronounced
      combined tobacco and alcohol consumption, the non-occupational risk factors
      increase exponentially and occupational risks attain marginal weight.

PMID- 12189575
TI  - [Identification of CD11c+ myeloid dentritic cells in adenoids and in nasal mucosa
      of patients with and without allergies].
AB  - BACKGROUND: Dendritic cells form a link between innate and acquired immunity.
      They are capable to detect pathogens based on the recognition of pathogen
      associated microbial molecules and trigger the appropriate type of immune
      responses. In humans, three major subsets of dendritic cells can be
      distinguished, Langerhans cells of the skin, myeloid DC (MDC) and plasmacytoid DC
      (PDC). It was reported that PDC infiltrate nasal mucosa in allergen-induced
      rhinitis. Information about the role of MDC in nasal mucosa and the corresponding
      mucosa-associated lymphoid tissue, the nasopharyngeal adenoids, is limited.
      PATIENTS AND METHODS: : Here we examined the presence of MDC in adenoids and in
      nasal mucosa of healthy individuals (n = 9) and in patients with allergic
      rhinitis. MDC were detected by flow cytometry by positive staining for MHC II and
      CD11c and the lack of lineage markers. Dead cells were excluded from analysis.
      RESULTS: In adenoids, 0.4 % of all cells were MDC. Considerable numbers of MDC
      could also be detected in nasal mucosa. No difference was found between healthy
      individuals and patients with allergies (0.3 % vs. 0.45 % MDC; p = 0.12).
      Interestingly, MDC were absent in patients who received treatment with
      glucocorticoids, while very high numbers of MDC were found in patients who
      recently had upper respiratory tract infections. CONCLUSION: Our results
      demonstrate for the first time the presence of MDC in nasal mucosa. MDC numbers
      were similar in healthy individuals and in patients with allergy. This study
      forms the basis for examining the role of MDC in the pathogenesis of allergic
      rhinitis, and for the modulation of MDC functional activity with microbial
      molecules such as CpG oligonucleotides.

PMID- 12189576
TI  - [Medicolegal screening of olfactory function].
AB  - Prior to nose surgery the birhinal ability to smell should be tested routinely.
      From the medico-legal point of view a short screening-test consisting of 5 or 8
      test items is not sufficient. It is recommended to use an identification test
      with 12 or 16 items. The results of these tests taken together with the patients'
      self estimation, the patients' history and the rhinoscopic findings offer a
      satisfactory evaluation of the patients' ability to smell in most cases. In case
      of discrepancies a more detailed test determining the TDI-value is recommendable.
      If the 16-identification test is used, it is sufficient to add the values of the
      threshold and the discrimination measurements with the "Sniffin' Sticks" to
      complete a full TDI score.

PMID- 12189577
TI  - [The monthly interesting case--Case No. 54. Chondrosarcoma of the larynx].

PMID- 12189578
TI  - [On the origin of neuronal nitric oxide [correction of carbon monoxide] of the
      cochlea].

PMID- 12189579
TI  - [Diagnosis and therapy of diseases of the larynx in the history of medicine. Part
      III. After the invention of laryngoscopy].
AB  - BACKGROUND: Laryngology a discipline of its own: When in 1855 Garcia had invented
      the indirect laryngoscopy and Turck and Czermak had introduced the method in
      clinical medicine numerous laryngological centres were founded in Austria,
      Germany, England, and France. FIRST INTERVENTIONS AND SOLUTION OF TECHNICAL
      PROBLEMS: In 1859 Czermak had already examined 20 patients with laryngeal
      diseases and demonstrated that it was possible to apply local treatment such as
      cautery under laryngoscopic view. The surgeon von Bruns in Tubingen (Germany)
      reported in 1862 on the successful removal of a polyp in the larynx. One common
      problem was the epiglottis preventing the view on the anterior part of the
      glottis. Czermak had suggested to make the epiglottis rise by intoning "hee".
      Methods of holding the epiglottis with a suture or with a forceps were not
      successful. In 1879 Reichert in Rostock (Germany) presented his epiglottis
      retractor which is still in common use. The irritability of the laryngeal mucosa
      remained the major problem for the next 20 years. CONSERVATIVE ENDOLARYNGEAL
      TREATMENT: The dominant means were local applications with brushes, powder
      blowers or injections of caustic fluids. Starting at about 1860 there were also
      steam inhalations. SURGICAL ENDOLARYNGEAL INTERVENTIONS: In a very early stage
      numerous instruments were devised such as sickle knives, various forceps, polyp
      snares and instruments for applications of electric currents. These were used in
      a monopolar and a bipolar way to induce electrolysis, coagulation and
      stimulation. INTRODUCTION OF SURFACE ANAESTHESIA: In 1884 in Vienna the surface
      anaesthesia with cocaine was introduced by Koller in the ophthalmology and by
      Jelinek in the laryngology. THE SPECIAL CASE HISTORY: The case history of the
      German emperor Frederick III, who died of laryngeal cancer in 1888, is briefly
      reported, because here all knowledge and technical facilities available at that
      time were brought into play. The treatment was guided by the German surgeons von
      Bergmann and Bramann, the laryngologists Gerhardt, Tobold and Schrotter (Vienna),
      the pathologists Virchow and Waldeyer, and the English laryngologist Mackenzie.
      The dominant problem was to have a safe diagnosis preoperatively. There was a
      passionate discussion about who was to blame for the fatal outcome of the
      emperor's disease. CONCLUDING: Another case history is reported when the surgeon
      von Bergmann believed he could demonstrate a successful operation on a patient
      with an apparently secure diagnosis of a laryngeal carcinoma the way it should
      have been done on the emperor. He was wrong: it turned out to be a tuberculosis
      and the patient died three hours after the operation.

PMID- 12189580
TI  - Feast or famine - are GLP-1 and ghrelin secretion intertwined?

PMID- 12189581
TI  - A polymorphism in the leptin promoter region (-2548 G/A) influences gene
      expression and adipose tissue secretion of leptin.
AB  - There is a large inter-individual variation in circulating leptin concentrations
      at each level of body fat content. The reason for this is unknown. We
      investigated whether a polymorphism in the promoter region of the leptin gene (
      2548G/A) influences gene transcription and leptin expression in 39 non-obese
      female subjects. Eleven subjects were homozygous for the AA genotype, 18 were
      heterozygous (GA) and 10 carried the GG genotype. AA subjects had higher levels
      of serum leptin than did GA/GG subjects (14.5 +/- 2.1 vs. 9.7 +/- 0.9 ng/ml, p =
      0.02). Adipose tissue leptin secretion rate in AA subjects was twice as high as
      in GA/GG subjects: 1158 +/- 288 vs. 626 +/- 84 ng/2 h/10 (7) cells (p = 0.02).
      These differences were also statistically significant with leptin levels adjusted
      for body mass index (p = 0.03 - 0.04). Adipose tissue leptin mRNA levels were 60
      % higher in AA subjects, as compared to GA/GG subjects, 74 +/- 10 vs. 46 +/- 4
      amol/ micro g RNA (p = 0.01). EMSA revealed that nuclear extracts derived from
      both U937 cells and human adipocytes form a protein-DNA complex with the leptin 
      2548G/A polymorphic site and bind with higher affinity to the -2548A-site. In
      conclusion, a common polymorphism in the promoter of the human leptin gene (
      2548G/A) influences leptin expression, possibly at the transcriptional level, and
      therefore also adipose secretion levels of the hormone.

PMID- 12189582
TI  - Regulation of glucose transport and transporter 4 (GLUT-4) in muscle and
      adipocytes of sucrose-fed rats: effects of N-3 poly- and monounsaturated fatty
      acids.
AB  - The goal of this study was to compare the short-term effects of dietary n-3
      polyunsaturated (fish oil) and monounsaturated (olive oil) fatty acids on glucose
      transport, plasma glucose and lipid controls in a dietary insulin resistance
      model using sucrose-fed rats. The underlying cellular and molecular mechanisms
      were also determined in the muscle and adipose tissue. Male Sprague-Dawley rats
      (5 weeks old) were randomized for diets containing 57.5 % (w/w) sucrose and 14 %
      lipids as either fish oil (SF), olive oil (SO) or a mixture of standard oils (SC)
      for 3 weeks. A fourth control group (C) was fed a diet containing 57.5 % starch
      and 14 % standard oils. After three weeks on the diet, body weight was comparable
      in the four groups. The sucrose-fed rats were hyperglycemic and hyperinsulinemic
      in response to glucose load. The presence of fish oil in the sucrose diet
      prevented sucrose-induced hyperinsulinemia and hypertriglyceridemia, but had no
      effect on plasma glucose levels. Insulin-stimulated glucose transport in
      adipocytes increased after feeding with fish oil (p < 0.005). These modifications
      were associated with increased Glut-4 protein (p < 0.05) and mRNA levels in
      adipocytes. In the muscle, no effect was found on Glut-4 protein levels. Olive
      oil, however, could not bring about any improvement in plasma insulin, plasma
      lipids or Glut-4 protein levels. We therefore conclude that the presence of fish
      oil, in contrast to olive oil, prevents insulin resistance and
      hypertriglyceridemia in rats on a sucrose diet, and restores Glut-4 protein
      quantity in adipocytes but not in muscle at basal levels. Dietary regulation of
      Glut-4 proteins appears to be tissue specific and might depend on insulin
      stimulation and/or duration of dietary interventions.

PMID- 12189583
TI  - Protein carbonyl content in erythrocyte membranes in type 2 diabetic patients.
AB  - Protein carbonyl groups result from free radical-induced protein oxidation; their
      level in tissues and plasma is a relatively stable marker of oxidative damage.
      Protein carbonyl contents in erythrocyte membranes were investigated in the type
      2 diabetic patients with good (n = 16) and poor (n = 30) glycemic control.
      Diabetic patients were classified as patients with (n = 20) and without (n = 26)
      angiopathy. Protein carbonyl content was evaluated using the 2,4-dinitro-phenyl
      hydrazine method. Protein carbonyl content and GHb levels were significantly
      higher in both patients with poor and good glycemic control than in control
      subjects (p < 0.001 in each case). There was a significant difference in protein
      carbonyl content between patients with poor and good glycemic control (p <
      0.001). Diabetic patients with angiopathy had significantly higher protein
      carbonyl content and GHb levels than the diabetic patients without angiopathy (p
      < 0.001). These results suggest that impaired glycemic control is connected to
      protein oxidation, and protein oxidation may be related to underlying metabolic
      abnormalities and complications of diabetes.

PMID- 12189585
TI  - Effects of dietary caloric restriction and aging on thyroid hormones of rhesus
      monkeys.
AB  - Plasma levels of thyroid hormones - triiodothyronine (T 3 ), thyroxin (T 4 ), and
      thyroid-stimulating hormone (TSH) were measured in male and female rhesus monkeys
      (Macaca mulatta) fed either ad libitum or a 30 % calorie-restricted (CR) diet
      (males for 11 years; females for 6 years). The same hormones were measured in
      another group of young male rhesus monkeys during adaptation to the 30 % CR
      regimen. Both long- and shorter-term CR diet lowered total T 3 in plasma of the
      monkeys. The effect appeared to be greater in younger monkeys than in older
      counterparts. No effects of CR diet were detected for either free or total T 4,
      although unlike T 3, levels of this hormone decreased with age. TSH levels also
      decreased with age, and were increased by long-term CR diet in older monkeys
      only. No consistent effects of shorter-term CR diet were observed for TSH. In the
      light of the effects of the thyroid axis on overall metabolism, these results
      suggest a possible mechanism by which CR diets may elicit their well-known
      beneficial 'anti-aging' effects in mammals.

PMID- 12189584
TI  - Aminoguanidine pyridoxal adduct is superior to aminoguanidine for preventing
      diabetic nephropathy in mice.
AB  - Aminoguanidine inhibits the formation of advanced glycation end-products, and has
      been extensively examined in animals. However, administration of aminoguanidine
      decreases the hepatic content of pyridoxal phosphate. In order to avoid this
      problem, we developed an aminoguanidine pyridoxal Schiff base adduct and examined
      its efficacy in vitro as well as in a model of diabetic nephropathy. Mice with
      streptozotocin-induced diabetes were treated with aminoguanidine or
      aminoguanidine pyridoxal adduct for 9 weeks. An in vitro study was also performed
      to assess the antioxidant activity of aminoguanidine and its pyridoxal adduct.
      Neither drug altered glycemic control. Aminoguanidine pyridoxal adduct
      significantly improved urinary albumin excretion by 78.1 % compared with the
      diabetic control, and also had a better preventive effect on the progression of
      renal pathology than aminoguanidine did. Inhibition of glycation by both drugs
      was similar, but the antioxidant activity of the pyridoxal adduct was far
      superior. These findings suggest that aminoguanidine pyridoxal adduct may be
      superior to aminoguanidine, as it not only prevents vitamin B6 deficiency but is
      also better at controlling diabetic nephropathy, as this adduct inhibits
      oxidation as well as glycation.

PMID- 12189586
TI  - Prediction of remission or relapse for Graves' hyperthyroidism by the combined
      determination of stimulating, blocking and binding TSH-receptor antibodies after
      the withdrawal of antithyroid drug treatment.
AB  - The most likely reasons for the low predictive value of TSH-receptor antibodies
      (TRAbs) determinations in previous investigations are the biological
      heterogeneity of TRAbs and changes of the different stimulating (TSAb) or
      blocking (TSBAb) antibody bioactivities of TRAbs during the course of Graves'
      disease (GD), which have not been taken into account in most previous studies.
      Furthermore, in a recent study it has been demonstrated that the decline of TRAb
      values detected with highly sensitive hTBII or TSAB assays is not useful in
      evaluating remission or relapse of GD at the end of antithyroid drug treatment
      (ATDT). In order to make a thorough investigation of the predictive values of all
      different TRAb qualities for the recurrence for GD after the withdrawal, we
      investigated hTBII, TSAbs and TSBAbs in 54 consecutive patients with GD at the
      end of ATDT and 12 - 13.5 months after stopping ATDT. Using the TRAb values at
      the time of reinvestigation in a model, recurrence for GD was better predicted
      compared to the determination at the time of withdrawal of ATDT. Furthermore,
      using this model, the combined determination of hTBII, TSAbs, and TSBAbs revealed
      the highest level of significance for the prediction of remission or relapse of
      GD (OR = 15; p < 0.0001) compared to the detection of hTBII, TSAbs and TSBAbs
      alone. Therefore, significant changes of TSAbs after the end of ATDT and the
      biological heterogeneity of TRAb define the conditions for predicting remission
      or relapse of GD after ATDT by TRAb determinations. Consequently, our results
      suggest that the prediction of the individual course of GD can only be improved
      by combined determinations of all TRAb qualities (hTBII, TSAbs and TSBAbs) after
      the end of ATDT.

PMID- 12189587
TI  - Effects of the beta3 adrenergic receptor agonist on developmental obesity in
      oophorectomized rats.
AB  - In this study, we evaluated the anti-obesity effects of selective beta3
      adrenergic receptor agonist (ARa) and/or a diet in oophorectomized (OVX)
      treatment in obese rats. Ten-week-old female Sprague-Dawley rats were divided
      into 4 groups: (1) OVX; (2) OVX treated with beta3 ARa, BRL 35 135; (3) sham
      operated controls (sham group); (4) sham-treated with beta3 ARa (sham+ARa group).
      These four groups were divided into two groups, one on ad libitum diet, and the
      other on a diet of limited chow. The effects of beta3 ARa on body weight,
      intraabdominal fat weight, adipocyte volume, serum lipid content, and serum
      leptin were measured after 4 weeks had been completed. On both the ad libitum and
      the limited diet, ARa significantly reduced the ratio of intraabdominal fat and
      body weight (IAF ratio) regardless whether in the OVX or sham group, although ARa
      had no influence on weight gain. On the ad libitum diet, the serum leptin was
      significantly increased after OVX, and significantly reduced after ARa
      administration. ARa significantly reduced the volume of intraabdominal
      adipocytes. We conclude that ARa reduces intraabdominal fat without reducing body
      weight in oophorectomized rats. The serum parameter affected differently to rats
      on the ad libitum diet and on the limited diet.

PMID- 12189588
TI  - Leptin and metabolic syndrome in obese and non-obese children.
AB  - Metabolic syndrome is characterized by a clustering of metabolic abnormalities:
      insulin resistance - hyperinsulinemia, dyslipidemia (high triglycerides and low
      HDL - cholesterol serum concentrations), impaired glucose tolerance and/or type 2
      diabetes, and hypertension. The aim of this study was to analyse the role of
      different variables of metabolic syndrome, including leptin, in 74 non-obese
      children and 68 children with non-syndromal obesity. As metabolic syndrome
      variables, we have included body mass index, waist circumference, trunk-to-total
      skinfolds (%), systolic blood pressure, diastolic blood pressure, glucose, uric
      acid, fasting insulin, triglycerides and high-density lipoprotein-cholesterol
      (HDL-C). Factor analysis showed 4 factors in each group. In non-obese children,
      waist circumference, BMI, fasting insulin, triglycerides, trunk-to-total
      skinfolds (%), leptin and uric acid loaded positively on factor 1, and HDL-C
      loaded negatively on this factor; systolic and diastolic blood pressure had high
      positive loadings in factor 2; HDL-C and leptin showed positive loadings and
      triglycerides and uric acid, negative loadings in factor 3; and, finally, glucose
      and insulin showed positive loadings in factor 4. These four factors explained
      72.16 % of the total variance in the non-obese group. In obese children, BMI,
      waist circumference, leptin, diastolic blood pressure and systolic blood pressure
      loaded positively on factor 1; diastolic blood pressure, trunk-to-total skinfolds
      (%), uric acid and systolic blood pressure showed high positive loadings in
      factor 2; fasting insulin, glucose and triglycerides showed positive loadings in
      factor 3; and, finally, triglycerides showed positive loadings and HDL-C negative
      loadings in factor 4. These four factors explained 74.18 % of the total variance
      in the obese group. Our results point to a different homeostatic control of
      metabolic syndrome characteristics in obese and non-obese children. Leptin seems
      to play a key underlying role in metabolic syndrome, especially in the obese
      group.

PMID- 12189589
TI  - Leptin treatment during the neonatal period is associated with higher food intake
      and adult body weight in rats.
AB  - For this study, we have determined the effects of neonatal leptin treatment on
      the evolution of body weight. Experiment 1: pups were divided into two groups:
      LepF - injected with leptin (8 micro g/100 g of body weight) for the first 10
      days of lactation and control (C) - receiving saline. Experiment 2: pups were
      divided into two groups: LepL - injected with the same leptin concentration of
      experiment one for the last 10 days of lactation, and C, which received saline.
      Body weight and food intake were monitored until age 150 days, after which leptin
      concentrations were measured by ELISA. The LepF group had a significant increase
      in body weight (p < 0.05) from day 98 onward, in food intake (p < 0.05) from day
      74 onward, and higher serum leptin concentration compared to the control (108 %,
      p < 0.05). The LepL group had a significant increase in body weight (p < 0.05)
      from day 113 onward, in food intake from day 121 onward (p < 0.001), and higher
      serum leptin concentration compared to controls (6.9 %, p < 0.05). These results
      suggest that both periods of lactation constituted a critical window for body
      weight and food intake programming, but the effects are more marked when the
      leptin is injected within the first ten days.

PMID- 12189590
TI  - Familial aggregation of body mass index: a population-based family study in
      eastern Finland.
AB  - In this study, we investigated the familial aggregation of body mass index (BMI)
      in a sample of families with young offspring from eastern Finland. 15-year-olds
      were examined from 1996 to 1997, and their biological parents were examined from
      1993 to 1994. 224 children were invited; 184 families participated, and 144 were
      included in the analysis with complete data. Significant positive correlations
      were found for mother-offspring pairs (correlation [r] = 0.31, p < 0.001, n =
      140), father-offspring (r = 0.23, p = 0.017, n = 107), mother-daughter (r = 0.26,
      p = 0.044, n = 63) and mother-son (r = 0.36, p = 0.001, n = 77). Adjustment for
      confounding variables did not alter these results. There was a higher proportion
      of children in the highest quartile of BMI when the mother was obese (odds ratio
      [OR] = 3.0, 95 % CI = 1.4 - 6.7, n = 140) and when one or both parents were obese
      (OR = 2.8, 95 % CI = 1.0 - 8.0 when one parent was obese; OR = 4.6, 95 % CI = 1.1
      - 20.0 when both parents were obese; n = 103). The study confirmed familial BMI
      aggregation. The consistent obesity relationship between mother and offspring may
      indicate the key role of the mother in primary obesity prevention.

PMID- 12189591
TI  - Circulating levels of ghrelin and GLP-1 are inversely related during glucose
      ingestion.

PMID- 12189592
TI  - No sizable inhibition of glucose-induced insulin secretion by acarbose and
      castanospermine.

PMID- 12189593
TI  - Lathosterolosis, a novel multiple-malformation/mental retardation syndrome due to
      deficiency of 3beta-hydroxysteroid-delta5-desaturase.
AB  - We report the clinical, biochemical, and molecular characterization of a patient
      with a novel defect of cholesterol biosynthesis. This patient presented with a
      complex phenotype, including multiple congenital anomalies, mental retardation,
      and liver disease. In the patient's plasma and cells, we found increased levels
      of lathosterol. The biosynthesis of cholesterol in the patient's fibroblasts was
      defective, showing a block in the conversion of lathosterol into 7
      dehydrocholesterol. The activity of 3beta-hydroxysteroid-Delta(5)-desaturase
      (SC5D), the enzyme involved in this reaction, was deficient in the patient's
      fibroblasts. Sequence analysis of the SC5D gene in the patient's DNA, showing the
      presence of two missense mutations (R29Q and G211D), confirmed that the patient
      is affected by a novel defect of cholesterol biosynthesis.

PMID- 12189594
TI  - Reference values for serum biochemical parameters in free-ranging harp seals.
AB  - BACKGROUND: The harp seal (Phoca groenlandica) is one of the most important
      predators in the Northeastern Atlantic ecosystem. Establishing biochemical
      reference intervals is important for evaluating the health status of harp seals
      kept in captivity and for evaluating the effects of environmental changes on the
      health of populations in the wild. OBJECTIVE: The purpose of this study was to
      determine reference values for serum biochemical parameters in wild adult harp
      seals using readily available current methods. METHODS: Blood samples were
      obtained from 14 adult female harp seals and 9 suckling pups on the pack ice of
      the Greenland Sea in early March 1998. Seven seals were humanely killed on the
      ice by permission of the Norwegian Directory of Fisheries and in conjunction with
      several other research projects. The seals were sampled within 15 minutes
      postmortem. Remaining seals were captured alive and sampled via the extradural
      intravertebral vein. Serum biochemical parameters were measured using a Technicon
      Axon analyzer and included electrolytes (sodium, chloride, potassium, magnesium,
      and calcium), substrates (free fatty acids, triglycerides, fructosamine, and
      glucose), end products (urea and uric acid), and proteins (total protein,
      globulins, and albumin). Serum protein electrophoresis also was done. Data were
      tested for normality and reference limits were calculated as mean +/- 1.96 X SD.
      Results between groups were compared using 2-tailed t-tests. RESULTS: Serum
      levels of glucose and triglycerides were lower, but serum levels of urea were
      higher in dead animals than in animals that were captured alive. Serum levels for
      7 of 17 parameters were significantly different in pups compared with adults.
      Separate reference intervals were calculated for adult seals and seal pups.
      CONCLUSION: Both sampling method and age should be considered when evaluating the
      results of future analysis of serum parameters in wild and captive harp seals.

PMID- 12189595
TI  - Blood values of juvenile northern elephant seals (Mirounga angustirostris)
      obtained using a portable clinical analyzer.
AB  - BACKGROUND: Sick, injured, or orphaned juvenile northern elephant seals (Mirounga
      angustisrostris) treated at rehabilitation centers frequently present with
      abnormalities in blood sodium, potassium, chloride, BUN, and glucose
      concentrations, and HCT. These abnormalities could be detected rapidly using a
      portable blood analyzer, but results with this analysis method do not necessarily
      equate with those obtained using other techniques. OBJECTIVE: The objective of
      this study was to better assess the clinical relevance of values obtained from a
      portable analyzer and to compare the results with values obtained using more
      common methods of analysis. METHODS: Heparinized whole blood samples were
      collected from 20 rehabilitated juvenile northern elephant seals. A portable
      clinical analyzer (i-STAT, i-STAT Corp, East Windsor, NJ, USA) was used to
      establish baseline values. Serum biochemical values were obtained using an
      automated chemical analyzer (Olympus AU5200, Olympus America, Melville, NY, USA).
      HCT was determined using EDTA whole blood and a cell counter. RESULTS: Using the
      portable analyzer, mean (minimum-maximum) values were obtained for sodium, 143
      (132-146) mmol/L; potassium, 4.4 (3.9-5.8) mmol/L; chloride, 106 (101-109)
      mmol/L; BUN, 1.8 (1.1-2.4) mmol/L; glucose, 7.55 (5.99-8.49) mmol/L; and HCT,
      0.55 (0.52-0.61) L/L. Average differences between methods were small for
      potassium (-0.45 mmol/L), BUN (0.1 mmol/L), and HCT (0.037 L/L) but were large
      for sodium (-6.8 mmol/L), chloride (-6.4 mmol/L), and glucose (-0.56 mmol/L).
      CONCLUSIONS: These results suggest that the i-STAT portable analyzer could be
      useful for clinically assessing juvenile elephant seals. However, when making
      medical decisions, the clinician should be aware of differences associated with
      various analyzers and sample types.

PMID- 12189596
TI  - Plasma biochemistry reference values of wild bonnethead sharks, Sphyrna tiburo.
AB  - BACKGROUND: Elasmobranchs (sharks, skates, and rays) are of commercial, sport,
      research, and exhibit importance, however, blood chemistry reference values have
      been determined for few of these species. OBJECTIVE: The purpose of this study
      was to establish plasma biochemistry and PCV reference values for wild bonnethead
      sharks (Sphyrna tiburo). METHODS: Heparinized blood samples were collected from
      24 bonnethead sharks at the time of capture in trawl nets off the coast of South
      Carolina and Georgia. Weight, length, PCV, total solids (TS, by refractometry),
      and plasma biochemical analyses were done using standard techniques. Wilcoxon
      rank-sum and Kendall tau b tests were used to compare values by animal size, boat
      and sex; 1-way ANOVA was used to compare TS and total protein (TP)
      concentrations. RESULTS: Median (quartile; minimum-maximum) values were as
      follows: PCV 22% (22%, 26%; 17-28%), TS 6.3 (6.0, 6.8; 5.8-7.5) g/dL, total
      protein 2.9 (2.7, 3.4; 2.2-4.3) g/dL, albumin 0.4 (0.4, 0.4; 0.3-0.5) g/dL,
      globulins 2.6 (2.3, 3.0;1.9-3.8) g/dL, sodium 282 (279, 285;273-292) mmol/L,
      potassium 7.3 (6.4, 7.9; 5.7-9.2) mmol/L, chloride 290 (285, 296; 277-304)
      mmol/L, total CO2 3 (2, 4; 0-5) mmol/L, calcium 16.8 (16.2, 17.4;15.8-18.2)
      mg/dL, phosphorus 8.8 (7.5, 10.0; 5.9-12.7) mg/dL, urea nitrogen 1004 (986, 1028;
      944-1068) mg/dL, creatinine <0.1 mg/dL, glucose 184 (165, 191; 155-218) mg/dL,
      aspartate aminotransferase 42 (33, 66; 15-132) U/L, lactate dehydrogenase <5 U/L,
      creatine kinase 82 (47, 233; 18-725) U/L, and osmolality 1094 (1078, 1111; 1056
      1139) mOsm/kg. No differences based on sex were detected. TS and TP values were
      related by the fitted line TS = (1.006 X TP) + 3.318. CONCLUSION: Values reported
      here will be useful for evaluating the health status of bonnetheads in wild and
      captive research conditions and in exhibits.

PMID- 12189597
TI  - Hematology, morphology, cytochemical staining, and ultrastuctural characteristics
      of blood cells in king cobras (Ophiophagus hannah).
AB  - BACKGROUND: King cobras (Ophiophagus hannah) have been captive-bred at Queen
      Saovabha Memorial Institute since 1996 to supply venom for antivenom production.
      Hematologic tests would be useful for evaluating the health of the snakes,
      however, basic hematologic data and morphology have not been described for this
      species. OBJECTIVE: The purpose of this study was to determine basic hematologic
      values and evaluate light microscopic, cytochemical, and electron microscopic
      characteristics of king cobra blood cells. METHODS: Blood samples from 13 wild
      caught and 15 captive-bred king cobras were collected into EDTA from the ventral
      caudal vein. A CBC was done using standard methods. Significant differences
      between groups were determined using t-tests. Cytochemical stains (periodic acid
      Schiff [PAS], Sudan black B [SBB], alpha-naphthyl acetate esterase [ANAE], acid
      phosphatase [AcP], and beta-glucuronidase [beta-glu]), and scanning and
      transmission electron microscopy were done using standard techniques. RESULTS:
      Eighteen snakes (64.3%) were positive for Hepatozoon infection. Hepatozoon
      organisms were detected nearly twice as frequently in wild-caught (11/13) as in
      captive-bred (7/15) snakes. Total WBC, azurophil, and lymphocyte counts were
      higher and fibrinogen concentration was lower in Hepatozoon-positive snakes.
      Captive-bred snakes had higher RBC values, lower azurophil, heterophil, and
      punctate reticulocyte percentages, and higher lymphocyte numbers compared with
      wild-caught snakes. Lymphocytes were the most commonly observed WBCs, and stained
      positive with PAS, ANAE, AcP, and beta-glu. Azurophil granules stained positive
      with SBB, PAS, and ANAE. Heterophils were the largest WBCs; their granules
      stained with SBB, ANAE, and beta-glu. Basophil granules stained with PAS, SBB,
      ANAE, and beta-glu. Thrombocytes were strongly positive with PAS. Transmission
      electron microscopic examination revealed organelles within all WBCs except
      eosinophils and revealed the gamonts of Hepatozoon sp in RBCs and azurophils.
      CONCLUSIONS: These results provide comparative hematologic data and a guide for
      identification of blood cells in wild-caught and captive-bred king cobra snakes.
      Hepatozoon infection was relatively common, but was not associated with severe
      hematologic abnormalities.

PMID- 12189598
TI  - Abdominal effusion in a bird.

PMID- 12189599
TI  - Blood smear from a wild-caught panther chameleon (Furcifer pardalis).

PMID- 12189600
TI  - Mortality in a wood turtle (Clemmys insculpta) collection.

PMID- 12189601
TI  - Granulomatous dermatitis in a spadefoot toad (Scaphiopus holbrooki).

PMID- 12189602
TI  - Clinical chemistry of companion avian species: a review.
AB  - Birds have evolved alternate physiologic strategies to contend with dehydration,
      starvation, malnutrition, and reproduction. Basic anatomic and functional
      differences between birds and mammals impact clinical chemistry values and their
      evaluation. Interpretation of the results of standard biochemical analyses,
      including BUN, alanine aminotransferase, aspartate aminotransferase, creatine
      kinase, gamma glutamyltransferase, bilirubin, ammonia, alkaline phosphatase,
      cholesterol, bile acids, glucose, albumin, globulins, calcium, phosphorus,
      prealbumin (transthyretin), fibrinogen, iron, and ferritin, is reviewed and
      discussed in relation to these physiological differences. The use and
      interpretation of alternative analytes appropriate for avian species, such as
      uric acid, biliverdin, glutamate dehydrogenase, and galactose clearance, also are
      reviewed. Normal avian urine and appropriate use of urinalysis, an integral part
      of laboratory diagnosis in mammalian species that frequently is omitted from
      avian diagnostic protocols, is discussed.

PMID- 12189603
TI  - Long-term results of percutaneous balloon dilation for ureterointestinal
      anastomotic strictures.
AB  - BACKGROUND: We determined the long-term result of our percutaneous antegrade
      balloon dilation technique performed for adult patients with ureterointestinal
      anastomotic stricture between 1992 and 1997. METHODS: Balloon dilation was
      performed on 13 ureterointestinal anastomotic structures in 10 patients. After a
      nephrostomy was performed, a guide wire was introduced into the intestinal loop
      through the stenotic portion under direct observation using a ureterorenoscope.
      Dilation was performed using the Olbert balloon dilator (30-Fr) inserted along a
      guide wire into the stenotic portion. A 20-Fr or 22-Fr multihole catheter was
      left for approximately 6 weeks. No major complications were encountered during or
      after these procedures. After removal of the indwelling catheters, the progress
      of each patient was followed fo rat least 14 months. RESULTS: Additional dilation
      was necessary in three of 10 patients for the recurrent stricture. The balloon
      dilation was ineffective in two patients with a long stenosis of the ureter or a
      previous history of radiation therapy for uterine cancer. Eight of 10 patients
      showed satisfactory outcomes during the mean follow-up period of 47.1 months.
      CONCLUSIONS: Based on these results, we believe that the balloon dilation could
      be the first line of treatment for strictures of uro-digestive anastomosis,
      except for some patients with a long stenosis or a previous history of
      intrapelvic radiation.

PMID- 12189604
TI  - Appendicovesicostomy for pubescent patients with neurogenic bladder using
      umbilicus as a stomal site.
AB  - We experienced two cases of neurogenic bladder in which clean intermittent
      catheterization (CIC) had been performed since early childhood. In both cases,
      CIC had not provided adequate voiding control and incontinence persisted.
      According to the Mitrofanoff Principle, we used the appendix as a catheterizable
      conduit, which was constructed to the umbilicus.

PMID- 12189606
TI  - Corneal graft rejection: recent updates.

PMID- 12189605
TI  - Topical nonsteroidal antiinflammatory drugs in ophthalmology.

PMID- 12189607
TI  - Masquerade syndromes: malignancies mimicking inflammation in the eye.

PMID- 12189608
TI  - Pathogenesis of Vogt-Koyanagi-Harada disease.

PMID- 12189609
TI  - Diagnostic imaging in patients with orbital cellulitis and inflammatory
      pseudotumor.

PMID- 12189610
TI  - Uveitis in sarcoidosis.
AB  - Sarcoid uveitis is common, mostly in a chronic form, and is prevalent in women
      past middle age. The onset is insidious. Inflammation is commonly mild but
      persists for a long period and then is complicated by the development of macular
      edema, cataract, and glaucoma, resulting in visual loss. The diagnosis is made
      according to characteristic ocular signs and systemic investigations. Effective
      treatment consists primarily of long-term use of steroids. Nonetheless, 15% of
      cases of sarcoid uveitis demonstrate an unfavorable visual outcome.

PMID- 12189611
TI  - Understanding corneal endotheliitis: an animal model approach.

PMID- 12189612
TI  - Helper T-cell subsets in uveitis.

PMID- 12189613
TI  - Neurovisual manifestations of herpesviruses.

PMID- 12189614
TI  - Diagnosis and management of herpetic anterior uveitis.
AB  - Herpetic anterior uveitis is a relatively common condition. History of herpetic
      disease and the presence of characteristic findings on ocular examination suggest
      the diagnosis and help to differentiate between HSV and VZV as the cause of this
      condition. New diagnostic techniques have allowed a more specific diagnosis.
      Topical corticosteroids and oral antivirals have become the main standards for
      management.

PMID- 12189615
TI  - A twenty-one year surveillance of adenoviral conjunctivitis in Sapporo, Japan.
AB  - We have studied the clinicoetiological, serological, and molecular
      epidemiological features of adenoviral conjunctivitis under the auspices of the
      nationwide surveillance project in Sapporo, located in northern Japan. We were
      able to analyze the results of 1,454 cases of adenoviral, herpetic, and
      chlamydial conjunctivitis. We found that adenonovirus serotypes 8, 19, and 37
      caused severe conjunctivitis without systemic symptoms, whereas serotypes Ad3,
      Ad7, and Ad11 caused mild conjunctivitis with systemic involvement. Ad4 showed a
      broad range of symptoms, from PCF to EKC. Adenoviral conjunctivitis had seasonal
      outbreaks in the summer in association with adequate temperature and humidity in
      Sapporo. Neutralization antibodies against Ad8, Ad19, and Ad37 were detected in
      fewer than 20% of cases, and so the incidence of epidemics with these serotypes
      may rise in the coming years. The main genome types of adenovirus in Sapporo were
      Ad4a, Ad8e, Ad19a, Ad19b, and Ad37p, a, and b.

PMID- 12189616
TI  - Ocular infections in patients with atopic dermatitis.

PMID- 12189617
TI  - Prevention of corneal ulceration in the developing world.

PMID- 12189618
TI  - Hypopyon uveitis in Japan.

PMID- 12189619
TI  - Rationale for mass antibiotic distribution for trachoma elimination.

PMID- 12189620
TI  - Postsurgical inflammation after bilateral cataract surgery using different
      intraocular lenses in each eye.

PMID- 12189621
TI  - Macrophage migration inhibitory factor in uveitis.
AB  - To summarize, we found that high levels of MIF were detected in the serum of
      uveitis patients with Behcet's disease, VKH disease, and sarcoidosis, as well as
      idiopathic iridocyclitis. In Behcet's disease and sarcoidosis, the MIF levels
      were higher in the active uveitis stage than in the inactive stage. Serum MIF
      increased after corticosteroid therapy in VKH disease. A high aqueous humor MIF
      concentration was detected at the onset of EAU. Finally, anti-MIF antibody
      suppressed EAU when administered in the early phase. MIF is thought to be an
      important cytokine in the pathogenesis of uveitis.

PMID- 12189622
TI  - [Phosphogliv: mechanism of therapeutic action and clinical efficacy].
AB  - The review summarizes the results of long term study (from design to clinical
      trial) of a new hepatoprotective drug Phosphogliv. Some theoretical ground for
      its creation has been considered with special emphasis on its ingredient
      properties: soy bean phosphatidylcholine and glycyrrhizinic acid from licorice
      roots. Experimental and clinical data concerning polyene phosphatidylcholine
      repairing action on cell membranes as well as antiviral and immunomodulating
      effects of glycyrrhizinic acid are presented. Their selected combination in
      Phosphogliv provided its high efficiency in rat hepatitis models. After standard
      toxicology tests it was allowed to carry out the clinical trials of this
      preparation in the treatment of liver diseases patients--mainly with acute and
      chronic viral hepatitis B, C, A and mixed hepatitis B + C (total 203 patients).
      The inclusion of Phosphogliv into therapy coarse accelerated disappearance of
      intoxication symptoms and decrease of serum aminotransferase and other hepatic
      markers. The effect was more pronounced for intravenous drug form.

PMID- 12189623
TI  - [Neurochemical basis of ultra rapid opioid detoxication].
AB  - Ultra rapid opioid detoxification (UROD) is a new technique with the use of mu
      opioid receptor antagonists to precipitate withdrawal. The scientific literature
      on UROD techniques in opiate addicts are reviewed, but little has been published
      on its neurochemical aspects. It is discussed that exposure to naloxone ore
      naltrexone during UROD is associated with development of increasing in
      opioidergic neurotransmission. On the other hand, ultra rapid opioid
      detoxification can be accompanied by normalization of joined brain
      neurotransmitter systems: noradrenergic, serotoninergic, GABAergic, cholinergic
      and glutamatergic neurotransmission systems. The neurochemical aspects of the new
      method detoxification are discussed.

PMID- 12189624
TI  - [Toxic effects of various water pollutants on structural and functional
      parameters of hepatocytes].
AB  - A prolonged intragastral intoxication of male and female rats by low doses of
      fluorine, zinc, chromium, arsenite, and combination of these compounds lead to
      developing cytolysis and hepatic-cellular insufficiency. These changes are more
      pronounced in female rats especially if chromium, arsenite and a combination of
      toxicants were used. They lead to developing hyper lipid peroxidation in male
      rats the most expressed by intoxication with arsenite and combined effect. Unlike
      to male rats LPO intensity in female rats was more pronounced and fixed by effect
      of all preparations. SOD activation was revealed to be in male rats by effect of
      chromium and especially zinc, in female rats by effect of fluorine and zinc. A
      distinctive inhibition of SOD activity determined to be by using arsenite and
      combination of toxicants. Activation of catalase especially in male rats was also
      revealed. Activation of membrane-destructive processes in the liver of
      experimental animals results in reducing pharmaco-metabolizing function of this
      organ.

PMID- 12189626
TI  - [Antioxidant system in rat tissues in hypothermia and dalargin introduction].
AB  - Total antioxidative activity, activity of water soluble fraction of antioxidative
      system, superoxide dismutase and catalase activities in brain, liver, myocard,
      skeletal muscle, kidney and serum at hypothermia 30 degrees C, 20 degrees C and
      self-warming from 20 degrees C to 37 degrees C were studied. Activity of
      antioxidative system is sustained at high level, except superoxide dismutase. The
      latter is activated significantly at 30 degrees C hypothermia prolonged up to 3
      h. Dalargin injection 30 min before onset of cooling stabilizes the erythrocyte
      membrane without enhancement of antioxidative activity in majority of
      investigated tissues.

PMID- 12189625
TI  - [Effect of stimulation and inhibition of macrophage functions on
      hypercholesterolemia in rats].
AB  - In this study we investigated the effects of zymosan and prodigiozan, the
      macrophage stimulators, and GdCl3, a macrophage inhibitor, on blood lipoprotein
      composition, activities of liver cholesterly ester (CE) metabolising enzymes,
      incorporation of [14C]cholesterol (C) into bile acids and accumulation and
      synthesis of CE in peritoneal macrophages (PM) of rats fed with C-enriched diet
      for 7 days. The increase of number of phagocyte cells quantity in liver and blood
      colony-stimulating activity in rats pretreated with intravenous injection of
      zymosan and prodigiozan was accompanied by reduced C content in blood low density
      and very low density lipoproteins (LDL and VLDL), increase of liver lysosomal CE
      hydrolase activity (without change of acyl-CoA:C acyltransferase and
      cytoplasmatic CE hydrolase activities) and incorporation of labeled C into bile
      acids and decrease of CE formation and accumulation in PM in rats with
      hypercholesterolemia. In contrast, reduction of phagocyte population in liver
      caused by intravenous injection of GdCl3 was accompanied by enhancement of C and
      CE level in blood LDL and VLDL and decrease of lysosomal CE hydrolase activity
      and incorporation of C into bile acids in liver of C-feeding rats. The data
      obtained suggest that the stimulation of mononuclear phagocyte system may lead to
      a decrease of plasma C via activation of LDL and VLDL catabolism and induction of
      bile acid synthesis in liver.

PMID- 12189627
TI  - [Stimulation of glucose uptake in PC 12 and L 929 cells by extracts from Aronia
      melanocarpa leaves].
AB  - The ability of extract from Aronia melanocarpa leaves to increase glucose uptake
      was investigated. It was shown, that the extract stimulated glucose uptake by
      cells PC12 and L 929 at the concentration close to native insulin.

PMID- 12189628
TI  - [Effect of oxidized indoles on monoamine oxidase activity in the rat brain
      mitochondria].
AB  - There is increasing evidence, that oxidized indoles, isatin, 5-hydroxyoxindole, 2
      oxindole, play important regulatory functions in the brain. Isatin and 5
      hydroxyoxindole share some common regulatory properties in cell cultures (Cane et
      al., 2000, BBRC, 276, 379), however, their effects on brain mitochondrial
      monoamine oxidases, a potential target for their action, have not been compared
      yet. Isatin acted as a rather selective monoamine oxidase B inhibitor, whereas 5
      hydroxyoxindole was more selective monoamine oxidase A inhibitor, but it was less
      potent than that of 5-hydroxyisatin, a synthetic analogue of isatin.

PMID- 12189629
TI  - [Changes in angiotensin-converting enzyme activity in pneumonia and chronic
      obstructive lung diseases].
AB  - The activity of angiotensin converting enzyme (ACE) was analysed in blood serum
      and bronchial fluid of 69 patients with acute pneumonia and 77 patients with
      chronic obstructive pulmonary diseases (COPD). In patients with pneumonia in
      acute phase ACE activity was lower in both serum and bronchial fluid. During
      recovery of patients with acute pneumonia ACE activity was normalizated. In
      patients with COPD ACE activity was lower in remission stage and higher (both
      serum and bronchial fluid) during COPD exacerbation. The changes of ACE activity
      were more pronounced in bronchial fluid than serum in both COPD and pneumonia.

PMID- 12189630
TI  - [Impairement of the platelet lipid membrane composition in severe angina
      pectoris].
AB  - Investigation was performed on 54 patients with angina pectoris. The patients
      were divided into three groups. Group 1 included patients with angina pectoris of
      functional classes I-II, group 2 consisted of the patients with angina pectoris
      classes III-IV, and group 3--unstable angina pectoris. All the patients underwent
      investigation of content and ratio of some fraction of the phospholipids and
      cholesterol metabolites in the thrombocyte membranes. Results of investigation
      showed damage of phospholipid metabolism of the thrombocyte membranes. This is
      manifested by increased in content of lysophosphatidylcholine (LPCh),
      phosphatidylserine (PS) and phosphatidyletanolamine (PEA), decreased levels of
      sphingomyelin (SM) and phosphatidylcholine (PCh). The angina pectoris of effort
      of the functional classes III-IV and unstable angina pectoris were manifested by
      severe damage of lipid metabolism in the thrombocyte membranes.

PMID- 12189631
TI  - [The use of complex interval models for predicting activity of non-nucleoside
      reverse transcriptase activity].
AB  - Searching of new anti-HIV agents is still crucial now. In general, researches are
      looking for inhibitors of certain HIV's vital enzymes, especially for reverse
      transcriptase (RT) inhibitors. Modern generation of anti-HIV agents represents
      non-nucleoside reverse transcriptase inhibitors (NNRTIs). They are much less
      toxic than nucleoside analogues and more chemically stable, thus being slower
      metabolized and emitted from the human body. Thus, search of new NNRTIs is actual
      today. Synthesis and study of new anti-HIV drugs is very expensive. So employment
      of the activity prediction techniques for such a search is very beneficial. This
      technique allows predicting the activities for newly proposed structures. It is
      based on the property model built by investigation of a series of known compounds
      with measured activity. This paper presents an approach of activity prediction
      based on "structure-activity" models designed to form a hypothesis about probably
      activity interval estimate. This hypothesis formed is based on structure
      descriptor domains, calculated for all energetically allowed conformers for each
      compound in the studied sef. Tetrahydroimidazobenzodiazipenone (TIBO) derivatives
      and phenylethyltiazolyltiourea (PETT) derivatives illustrated the predictive
      power of this method. The results are consistent with experimental data and allow
      to predict inhibitory activity of compounds, which were not included into the
      training set.

PMID- 12189632
TI  - Commentary on Cicchetti's "reliability of peer review".

PMID- 12189633
TI  - Teaching delivery of bad news using experiential sessions with standardized
      patients.
AB  - BACKGROUND: Delivering bad news is a difficult task that is important to address
      in medical education. PURPOSE: This study evaluated the impact of an experiential
      educational intervention using multiple standardized patient scenarios on medical
      students' comfort with delivering difficult news. METHODS: In small groups, 3rd
      year medical students practiced communicating bad news within the context of five
      different patient scenarios. During 1999 and 2000, surveys were administered to
      341 students before and 4 weeks and 1 year after the program. Students rated
      comfort level in discussing bad news, terminal illness, hospice, and dying with
      patients. RESULTS: A significant one standard deviation change was observed in
      students' self-reported comfort in communicating bad news after the educational
      program. The intervention was highly rated, especially the encounters with
      standardized patients and observation of others. CONCLUSIONS: Experiential
      education using multiple standardized patient scenarios is a successful model for
      increasing student comfort in responding to difficult clinical communication
      tasks.

PMID- 12189634
TI  - Comparison of an aggregate scoring method with a consensus scoring method in a
      measure of clinical reasoning capacity.
AB  - BACKGROUND: Diversity of clinical reasoning paths of thought among experts is
      well known. Nevertheless, in written clinical reasoning assessment, the common
      practice is to ask experts to reach a consensus on each item and to assess
      students on a unique "good answer." PURPOSES: To explore the effects of taking
      the variability of experts answers into account in a method of clinical reasoning
      assessment based on authentic tasks: the Script Concordance Test. METHODS: Two
      different methods were used to build answer keys. The first incorporated
      variability among a group of experts (criterion experts) through an aggregate
      scoring method. The second was made with the consensus obtained from the group of
      criterion experts for each answer. Scores obtained with the two methods by
      students and another group of experts (tested experts) were compared. The domain
      of assessment was gynecology-obstetric clinical knowledge. The sample consisted
      of 150 clerkship students and seven other experts (tested experts). RESULTS: In a
      context of authentic tasks, experts' answers on items varied substantially.
      Amazingly, 59% of answers given individually by criterion group experts differed
      from the answer they provided when they were asked in a group to provide the
      "good answer" required from students. The aggregate scoring method showed several
      advantages and was more sensitive to detecting expertise. CONCLUSIONS: The
      findings suggest that, in assessment of complex performance in ill-defined
      situations, the usual practice of asking experts to reach a consensus on each
      item reduces and hinders the detection of expertise. If these results are
      confirmed by other researches, this practice should be reconsidered.

PMID- 12189635
TI  - Using differences between perceptions of importance and competence to identify
      teaching needs of primary care preceptors.
AB  - BACKGROUND: An important goal of a comprehensive faculty development plan is to
      improve teaching. This is especially important for clinical preceptors. PURPOSE:
      This study used a novel approach to assessing the teaching needs of preceptors,
      an essential and often neglected first step in faculty development. Measurement
      focused on discrepancies between importance and current performance related to a
      rich variety of teaching behaviors. This study also considered differences in
      perceived teaching needs among primary care specialties. METHOD: Twenty-six
      clerkship directors from 13 participating medical schools in the Northeast United
      States invited randomly selected family medicine, internal medicine, and
      pediatric preceptors to complete a teaching needs survey. One hundred five
      preceptors responded. RESULT: Findings revealed that preceptors most need to
      develop general teaching skills that will help them save time such as selecting
      appropriate teaching behaviors, assessing learners' needs and providing
      appropriate feedback, and helping learners learn independently. On the other
      hand, preceptors expressed less need to improve teaching related to cost
      containment, disease prevention, clinical decision making, office management, and
      using computers to aid teaching. Family practice preceptors rated their current
      teaching performance significantly higher than pediatric preceptors despite no
      differences in previous faculty development experience. CONCLUSION: Faculty
      development for preceptors should focus on general teaching skills relative to
      teaching skills tied to specific medical areas. Novel approaches to teaching
      while practicing medicine that increase efficiency should be explored. Faculty
      developers should consider differences in confidence among preceptors from
      different specialties.

PMID- 12189636
TI  - 1st- and 2nd-year medical student exposure to emergency medicine.
AB  - BACKGROUND: Medical societies in emergency medicine (EM) have recommended
      teaching EM topics in the preclinical years of medical school. However, the
      magnitude of integrating an EM curriculum into the 1st and 2nd year of medical
      school is unknown. PURPOSE: The purpose of this survey was to determine the
      extent and type of exposure to EM in the 1st and 2nd years of medical schools in
      the United States. METHODS: The deans of all allopathic and osteopathic medical
      schools in the country were surveyed by mail. The survey took the form of a
      questionnaire and had seven questions that included type of exposure, number of
      students, length of the exposure, learning objectives, lectures, laboratory,
      textbook, evaluation process and grades, departmental status, board
      certification, emergency department volume, and size of the medical school class.
      The data were analyzed with SPSS software. RESULTS: The survey was returned by 84
      of the 125 (67.2%) medical schools in the country. The average class size was
      129.0 students. As many as 63.9% of the medical schools responding provided EM
      exposure in the 1st year and 54.3% in the 2nd year. The 1st-year exposure most
      frequently used more than one type of teaching activity (47.4%), observation
      (12.3%), cardiopulmonary resuscitation training (15.8%), universal precautions
      (7.0%), and other (17.5%). None taught physical diagnosis. The various teaching
      activities lasted anywhere from hours (27.5%), to days (25.3%) or weeks (52.5%),
      with a mean of 2.25 weeks. Second-year exposure most frequently included multiple
      activities (49.0%), observation (16.3%), or other activities (14.3%); a few
      taught physical diagnosis (8.2%), cardiopulmonary resuscitation training (6.1%),
      or universal precautions (6.1%). These teaching activities lasted from hours
      (20.6%), to days (14.7%) or weeks (64.7%), with a mean of 2.44 weeks.
      CONCLUSIONS: Most U.S. medical schools provide EM exposure in the first 2 years
      of medical school, lasting slightly more than 2 weeks in length most frequently
      covering multiple topics.

PMID- 12189637
TI  - Attitudes toward tuberculosis of final year medical students from Canada, India,
      and Uganda.
AB  - BACKGROUND: Tuberculosis, although both preventable and treatable, continues to
      be the world's leading cause of death from an infectious agent. PURPOSE: To
      extend the results of our previous study of knowledge and practices of final year
      medical students regarding tuberculosis at three medical schools from endemic and
      nonendemic areas and to describe their attitudes. METHODS: Eight statements
      assessing attitudes, as part of a larger survey, were administered to final year
      medical students at McMaster University in Canada, Christian Medical College in
      India, and Makerere University in Uganda. RESULTS: One hundred sixty surveys were
      returned with 155 completed attitude responses. The response rate was 68.4% (65
      of 95) for McMaster University, 39.7% (23 of 58) for the Christian Medical
      College, and 78.3% (72 of 92) for Makerere University. Analysis showed that six
      of eight attitude items were slightly statistically different among the schools
      with minimal effect of curriculum time and patient exposure. CONCLUSIONS: Despite
      quite varied exposure to tuberculosis, students from endemic and nonendemic areas
      responded similarly on statements addressing attitudes toward tuberculosis.

PMID- 12189638
TI  - Attrition rates of residents in postgraduate training programs.
AB  - BACKGROUND: One goal of program directors is to attract and retain high-quality
      residents. It is therefore important to study attrition of residents to determine
      specific cohorts that may be less likely to complete residency training. PURPOSE:
      The purpose of this study was to investigate attrition rates in targeted
      programs. METHOD: Surveys were sent to 540 program directors whose programs
      contained at least 25% international medical graduates. The program directors
      reported both voluntary attrition and termination rates. RESULTS: Overall
      attrition rates for international medical graduates and U.S. medical graduates
      were similar, although U.S. medical graduates were terminated at a slightly lower
      rate than international medical graduates (2.5% vs. 3.6%) and were somewhat more
      likely to transfer to other programs (9.9% and 8.9%). CONCLUSIONS: Attrition from
      these programs remains a small but persistent issue. In addition, the differences
      in termination and transfer rates for the 2 years of the study were greater than
      the differences in rates between U.S. and international medical graduates.

PMID- 12189639
TI  - Community-based education and problem solving: the Community Health Scholars
      Program at the University of Florida.
AB  - BACKGROUND: Although many medical schools understand and support the need for
      community service as part of educational training, this goal has been difficult
      to operationalize. DESCRIPTION: The Community Health Scholars program, a joint
      effort between the Area Health Education Center and the University of Florida,
      places 1st-year medical students in clinical settings with underserved
      populations, both rural and urban. The stated goal of the experience is to solve
      a problem identified by the communities as well as provide exposure to community
      practice and environment. EVALUATION: The program provided notable services to
      many communities. More than 80% of participating students believed it was a good
      or excellent learning experience; more than 90% believed that the program
      affected their career choice; and 100% believed that the program should be
      continued. Although this is a 1st-year program, students were not surveyed until
      their last year, suggesting that the program may have a lasting effect.
      CONCLUSIONS: This collaborative program successfully provided a service-learning
      experience for students while promoting solutions to problems in underserved
      communities.

PMID- 12189640
TI  - An organizational innovation: the Yale Primary Care Residency Program's
      experience with a firm system.
AB  - BACKGROUND: Integrated inpatient-outpatient firms developed in residencies with
      single institutions may not be applicable to residency programs with multiple
      inpatient and outpatient training sites. Our objective was to develop a firm in a
      multisite residency program that improved education and patient care.
      DESCRIPTION: One ward team was restructured into a firm that included two
      interns, three residents, and four private practice internists whose patients
      were admitted to the firm. Educational impact, length of stay, hospital charges,
      and in-hospital mortality were evaluated. EVALUATION: The firm experience
      increased outpatient training, fostered mentoring relationships, and increased
      attending availability. Mean length of stay (5.7 vs. 6.5 days, p = .2) and mean
      hospital charges ($10,888 vs. $12,316, p = .8) for firm and nonfirm patients,
      respectively, were not different. In-hospital mortality was lower for firm
      patients (9 of 348, 3%, vs. 87 of 1,565, 6%; p = .02). CONCLUSIONS: Firm
      structures with educational and patient care advantages can be instituted in
      multisite residencies.

PMID- 12189641
TI  - The role of interactive training skills courses in medical education at the
      Ankara University School of Medicine.
AB  - BACKGROUND: The Department of Medical Education at Ankara University School of
      Medicine offered a teaching program for their physician educators. One hundred
      and fifty professors from different disciplines attended this 5-day training
      course. DESCRIPTION: Two certified master trainers designed the program, which
      consisted of the following topics: adult learning principles, creating a positive
      training climate, interactive training techniques, clinical demonstration,
      coaching principles, effective use of audiovisual materials, developing and using
      knowledge and competency-based assessment instruments, and organizing training
      sessions. Master trainers managed all the courses and guided the other trainers
      according to the principles of group dynamics. Of the overall participants, 30%
      attended voluntarily (n = 45) and 70% attended compulsorily (n = 105).
      EVALUATION: In general, 97.5% to 100% assessed the course as either good or very
      good, with no difference in assessment between the two groups (p > .05; one-way
      analysis of variance). Course topics and time arrangements for each training
      session were rated optimal by 82% of participants, and all of them recommended
      that "all faculty should attend this course." CONCLUSION: The positive effects of
      these courses have led the School of Medicine's academic council to agree by
      consensus to accept the training skills course certificate as a criterion for
      eligibility to become a trainer at the School of Medicine. They also decided to
      institute educational reform, including changing the curriculum and using new
      educational methodology such as interactive techniques and problem-based
      learning.

PMID- 12189642
TI  - Developments in the instruction of biostatistics at the Kuwait University Health
      Science Centre in a decade.
AB  - BACKGROUND: Kuwait has witnessed many changes that influenced, among other
      things, the structure of medical education including biostatistics. This article
      describes the developments in biostatistics instruction and curriculum in the
      Health Science Centre, University of Kuwait, during the past 10 years.
      DESCRIPTION: Instead of teaching biostatistics as an independent component, the
      university has developed an integrated course (35 hr of lectures and 12 hr of
      tutorial sessions) of biostatistics, epidemiology, and demography that is taught
      to undergraduate medical and dentistry students to ensure interdisciplinary
      interaction, to remove redundancies, and to standardize terminology across the
      three disciplines. The core curriculum of the biostatistics course is compatible
      with the recommendations of the American Statistical Association. Separate
      biostatistics courses are also offered to pharmacy and allied health students to
      address their diverse interests. In addition, new biostatistics and computer
      applications instruction courses were developed and are taught to the students of
      the Master of Science (MSc), Master of Public Health (MPH), and PhD programs. For
      continuing medical education, a workshop on biostatistics and computer
      applications is organized annually for the medical profession as a collaboration
      between the Health Science Centre and the Kuwait Institute for Medical
      Specialization. EVALUATION: The instructor and curriculum content of the
      biostatistics courses are confidentially evaluated and independently analyzed by
      the office of the Vice Dean for Academic Affairs. Overall, students evaluate the
      biostatistics instructors highly and are pleased with the content of the
      biostatistics curriculum. CONCLUSIONS: During the last decade, biostatistics
      instruction in the Kuwait Health Science Centre had many new developments. An
      integrated course on biostatistics, epidemiology, and demography was developed
      with emphasis on problem solving and small group learning. Another biostatistics
      course is offered to the students of the new faculty of pharmacy. Further
      biostatistics courses became operational for the postgraduate programs: (MSc),
      (MPH), and PhD. Continuing medical education is supported by workshops, which is
      a sign of collaboration with the health community, and a consultancy office has
      been established. Overall, biostatistics instruction is well received by
      students, and the role of biostatistics is recognized by researchers from the
      medical profession.

PMID- 12189643
TI  - Clinical manifestations and complications of rickettsiosis in southern Taiwan.
AB  - BACKGROUND AND PURPOSE: Taiwan is an endemic area for scrub typhus. Recent
      increases have been noted in two other infectious diseases caused by obligate
      intracellular organisms, Q fever and murine typhus. These diseases usually
      present as an acute febrile illness with non-specific symptoms and are difficult
      to distinguish. This study describes the clinical manifestations and
      complications of cases of rickettsial infections treated at a medical center in
      southern Taiwan. METHODS: Serum samples from patients with acute febrile illness
      with or without shock, but without a clinical diagnosis of localized bacterial
      infection after a preliminary work-up, were collected for serologic study.
      Medical records of cases with serologic evidence of infection were reviewed and
      their clinical manifestations were analyzed. RESULTS: From October 1992 to July
      2000, 51 serologically diagnosed cases of rickettsiosis were studied. Q fever
      predominated (28 cases). All cases of acute Q fever presented with hepatitis
      during the course of the illness and more than half (54%) reported an animal
      contact history. Most patients with Q fever (96%) and murine typhus (86%) were
      male, Serious complications, especially pneumonitis, occurred more frequently
      with scrub typhus than with acute Q fever. Spontaneous remission frequently
      occurred with acute Q fever. Administration of tetracycline or its analogues
      usually resulted in defervescence by the third day of treatment of scrub typhus.
      CONCLUSIONS: In our study, serious complications including pneumonitis,
      meningitis/meningoencephalitis, shock, acute renal failure, and disseminated
      intravascular coagulation were not uncommon in patients with scrub typhus.
      Physicians should include scrub typhus in the differential diagnosis of suspected
      cases of community-acquired febrile illness with multiple organ dysfunction in
      this endemic area. As Q fever is an emerging infectious disease in southern
      Taiwan, further large-scale epidemiologic surveillance and clinical data are
      needed.

PMID- 12189644
TI  - High incidence of CD56 expression and relapse rate in acute myeloid leukemia
      patients with t(8;21) in Taiwan.
AB  - BACKGROUND AND PURPOSE: CD56 is a marker of natural killer cells, but can also be
      found on blast cells in acute myeloid leukemia (AML). The prognostic implications
      of CD56 expression in AML are not clear. In this study, we evaluated the
      correlation among CD56 expression, cytogenetic abnormality, and clinical outcome
      in AML. METHODS: CD56 expression was analyzed in leukemic cells from 94 adults
      with primary AML in Taiwan and was correlated with clinical and hematologic
      features, cytogenetics, and immunophenotypes of the leukemia. RESULTS: Thirty
      patients (32%) showed CD56 expression. CD56+ AML patients had a higher lactate
      dehydrogenase level than CD56- patients (1.136 vs 730 V/L, p = 0.048). Patients
      with t(8;21) had a significantly higher incidence (89%, 8/9) of CD56 positivity
      in leukemic cells than those with normal karyotype or other cytogenetic
      abnormalities (26%, 22/85, p < 0.001). In general, there was no difference in
      overall survival time in CD56+ and CD56- AML patients. However, three patients
      had central nervous system involvement at initial presentation; two of these had
      concomitant CD56 expression and t(8;21). In addition, five of the seven patients
      with t(8;21) and CD56 expression who achieved complete remission later relapsed.
      CONCLUSIONS: The incidence of CD56 expression in AML patients with t(8;21) is
      very high in Taiwan, and it may imply a poor prognosis in this subgroup of
      patients.

PMID- 12189645
TI  - Self-expandable metallic tracheobronchial stent insertion and endobronchial
      electrocautery with flexible bronchoscopy: preliminary results at a cancer
      center.
AB  - BACKGROUND AND PURPOSE: Technical developments have facilitated the implantation
      of metallic stents and the use of endobronchial electrocautery through a flexible
      bronchoscope to reestablish airway patency in patients with airway obstruction.
      Their application in a 180-bed cancer center is described. PATIENTS AND METHODS:
      From August 2000 to December 2001, 12 patients (2 women, 10 men, mean age 53.3
      yr) were treated by insertion of a self-expandable metallic tracheobronchial
      stent (SEMS). Malignant airway obstruction was the indication for the procedure
      in nine patients, two of whom underwent preliminary debulking using SEMS with or
      without electrocautery. Severe benign subglottic or tracheal stenosis was the
      indication for the procedure in two patients. The remaining patient with
      esophageal cancer received a double bronchial and esophageal SEMS due to
      involvement of a non-obstructing bronchoesophageal fistula. RESULTS: Symptomatic
      improvement was seen in all 12 patients. Removal was performed in one patient.
      Five patients died during follow-up with a median survival of 44 days, attributed
      to the advanced stage of recurrent disease. The median follow-up for the six
      surviving patients was 23 weeks. No major short-term complications of the
      procedure were found. CONCLUSIONS: SEMS is a promising technique for the
      management of airway obstruction. The stent is selected according to the specific
      clinical situation. Metallic and silicone stents are complementary. SEMS should
      not be used in patients who require only temporary relief of tracheobronchial
      obstruction.

PMID- 12189646
TI  - Comparison of predictive accuracy among six prognosis prediction systems for
      patient mortality in intensive care units.
AB  - BACKGROUND AND PURPOSE: This study compared the goodness-of-fit of six prognostic
      prediction systems. METHODS: A total of 1,170 patients in the medical and
      surgical intensive care units of a public tertiary care hospital were included in
      this study. Data from the Acute Physiology and Chronic Health Evaluation (APACHE)
      II, APACHE III, Simplified Acute Physiology Score II (SAPS II), Condition Index
      Score (CIS), and Mortality Probability Models II (MPM II; at admission MPM IIadm
      and 24-hours later MPM II24 h) prediction systems were collected. The scores or
      death-risks from these systems were compared between survivors and non-survivors.
      Lemeshow-Hosmer (LH) statistics, calibration curve, classification matrix, and
      receiver operating characteristic (ROC) curve for the whole study group were
      determined. Mortality ratio, LH statistics, and ROC curve for individual disease
      categories and operative states were compared. A model with good fit was defined
      as having an LH chi-square value close to the degrees of freedom and yielding a
      corresponding p value of greater than 0.05, conformation to the ideal calibration
      diagonal (low deviation value), high classification matrix overall accuracy, a
      large area under the ROC curve (> 0.8), and a mortality ratio close to 1.
      RESULTS: LH chi-square value was 12.37 for APACHE II and 8.61 for MPM II24 h. The
      calibration curve deviation value was 1.5069 for APACHE II and 1.4308 for MPM
      II24 h. Classification matrix overall accuracy was 78.88% for APACHE II and
      79.54% for MPM II24 h. The area under the ROC curve was 0.779 for APACHE II and
      0.790 for MPM II24 h. The mortality ratios of trauma were 1.00 for both APACHE II
      and MPM IIadm. The mortality ratios for respiratory diseases and rare diseases
      were both 1.02 for MPM II24 h. The other systems studied did not provide good-fit
      data. CONCLUSION: In this study, MPM II or APACHE II had the best predictive
      model of the tested systems for critically ill patients.

PMID- 12189647
TI  - One-stage correction of congenital complex penile curvature by tunica albuginea
      plications.
AB  - BACKGROUND AND PURPOSE: Congenital complex penile curvature has two deformity
      components: torsion and curvature of the penile shaft. Limited cases have been
      reported and were managed with an invasive Nesbit procedure. We introduce a novel
      simple surgical technique to correct the deformity in one stage. PATIENTS AND
      METHODS: Plications of the tunica albuginea were applied to treat five patients
      (median age, 28 yr) with congenital complex penile curvature. Mean follow-up
      duration was 14 months (range, 9-20 mo). In the first case, penile curvature was
      corrected first followed by the torsion. In the other four cases, the sequence
      was reversed. A parabolic curve was made from the subcoronal area crossing the
      dorsal midline and extending toward the penile base obliquely to the direction of
      counter-torsion. Along the curve, two points (one at the maximum convexity and
      the other depending on the type of curvature) were chosen for plications to
      correct torsion. The remaining curvature was corrected subsequently. RESULTS: It
      took five plications to accomplish a satisfactory result in the first case. In
      the other four cases, only three plications were needed to correct the deformity.
      In all five patients, penile deformities were corrected successfully with either
      residual torsion or curvature being no more than 5 degrees. All patients were
      satisfied with excellent cosmetic and functional results with no recurrent
      curvature or torsion. All patients had started successful sexual intercourse
      shortly more than 2 months after the operation without erectile problems. One
      patient reported a mild sensory impairment of the penile skin that resolved 2
      months later. CONCLUSIONS: By correcting penile torsion and curvature in sequence
      with plications of the tunica albuginea, congenital complex penile curvature can
      be corrected in a one-stage operation with good cosmetic and functional results.

PMID- 12189648
TI  - Multiple myeloma with myeloma nephropathy in a patient with Hashimoto's
      thyroiditis.
AB  - Hashimoto's thyroiditis is associated with myeloproliferative and
      lymphoproliferative neoplasms. The risk of carcinoma of the thyroid gland is
      increased in these patients. Furthermore, multiple myeloma can present together
      with some autoimmune diseases. We report the case of a 57-year-old woman with
      Hashimoto's thyroiditis who developed multiple myeloma with myeloma nephropathy.
      Her renal function deteriorated to end stage and she required maintenance
      hemodialysis. Although autoimmune disorder might play an important role in
      lymphomagenesis in patients with Hashimoto's thyroiditis, it is not known whether
      the chronic inflammation that takes place in Hashimoto's thyroiditis stimulates
      the development of multiple myeloma. The pathogenetic mechanisms responsible for
      the development of multiple myeloma in patients with Hashimoto's thyroiditis
      remain unclear.

PMID- 12189649
TI  - Mucopolysaccharidosis type I: Identification and characterization of mutations
      affecting alpha-L-iduronidase activity.
AB  - Mucopolysaccharidosis type I (MPS I) is caused by a deficiency of the lysosomal
      enzyme alpha-L-iduronidase (IDUA). MPS I covers a broad spectrum of clinical
      severity ranging from severe Hurler syndrome through intermediate Hurler/Scheie
      syndrome to mild Scheie syndrome. Mutation screening was performed in two
      unrelated Taiwanese MPS I patients. A Hurler/Scheie patient had A79V (C to T
      transition in codon 79) in exon 2 and R619G (C to G transversion in codon 619) in
      exon 14. R619G has been shown to cause disease. Expression of A79V in COS-7 cells
      showed trace amounts of IDUA activity, demonstrating the deleterious nature of
      the mutation. A79V mutation did not cause a reduction in IDUA mRNA levels. The
      reduced level of IDUA protein suggests increased degradation of the mutant
      enzyme. A Hurler patient had 134del12 (in-frame deletion of codons 16-19 in
      signal peptide) in exon 1 and Q584X (C to T transition in codon 584) in exon 13.
      Transfection of COS-7 cells with Q584X did not yield active enzyme. Q584X
      mutation caused an apparent reduction in the IDUA mRNA level and no IDUA protein
      was detected. Conversely, 134del12 showed 124.6% of normal activity in
      transfected cells and a 77-kDa precursor protein was observed on Western blot,
      suggesting biologic activity of precursor IDUA without posttranslational
      cleavage. These findings provide further evidence of the molecular heterogeneity
      in mutations in MPS I.

PMID- 12189650
TI  - Rhabdomyolysis associated with Streptococcus pneumoniae bacteremia in a
      splenectomized patient.
AB  - Invasive infection due to Streptococcus pneumoniae associated with rhabdomyolysis
      is rare. We report the case of a 31-year-old splenectomized man with pneumococcal
      bacteremia and paranasal sinusitis who presented with flu-like symptoms preceding
      a fulminant course of sepsis and rhabdomyolysis with acute renal failure and
      elevated creatinine phosphokinase. Although the possible mechanisms of
      rhabodomyolysis associated with pneumococcal infection remain unclear, this
      report may serve to alert clinicians of the need to prevent fulminant
      pneumococcal infection by vaccination and treatment with antibiotic prophylaxis
      in splenectomized patients.

PMID- 12189651
TI  - Postpartum endogenous Candida endophthalmitis.
AB  - Candida albicans is the most common pathogen causing intraocular fungal
      infection. Postpartum endogenous Candida endophthalmitis, however, is extremely
      rare. We report the case of a 33-year-old postpartum woman who presented with a 5
      day history of decreased vision and had a positive blood culture for C. albicans.
      Fundus examination showed vitreous haze and multiple pre-retinal whitish lesions
      with indistinct borders. Systemic investigations revealed acute renal failure and
      cardiomegaly. After treatment with intravenous antifungal therapy, vitrectomy,
      and intravitreal injection of antimycotics, systemic and intraocular infections
      were eradicated successfully.

PMID- 12189652
TI  - Pedunculated hepatic hemangioma: report of two cases.
AB  - Pedunculated hepatic hemangioma may be confused with pedunculated hepatocellular
      carcinoma (HCC) in clinical practice because of their similar ultrasonographic
      pattern. We report two cases of asymptomatic pedunculated hepatic hemangioma.
      Both patients presented with intraabdominal masses of unknown nature measuring
      about 5 cm in diameter. Pedunculated HCC was suspected because of a pedicle and
      ultrasonographic pattern in both patients, positive hepatitis B surface antigen
      as a risk factor in one patient, and the high prevalence of HCC in Taiwan.
      Diagnosis was established by computerized tomography, magnetic resonance imaging,
      radionuclide scintigraphy, and angiography in both patients and confirmed by
      histopathology of the surgical specimen in one patient. Pedunculated hepatic
      hemangioma should be included in the differential diagnosis of a mass located in
      the upper abdomen.

PMID- 12189653
TI  - Potential pool of non-heart-beating kidney donors in Taiwan: chart review in a
      regional hospital.
AB  - The annual number of renal transplantations performed in Taiwan is strictly
      limited by the availability of donor organs. One way to expand the donor pool is
      the use of non-heart-beating (NHB) donors. This study evaluated the potential
      number of NHB kidney-donors in Taiwan using a retrospective death chart review
      from a regional hospital in patients who died between January 1 and December 31,
      1999. Exclusion criteria were extremities of age, systemic infection,
      malignancies other than primary brain tumor, uncontrolled diabetes mellitus,
      hypertension, kidney disease, or deaths with incomplete records. Detailed
      biomedical data of potential donors were collected. Of the 840 in-hospital
      deaths, 258 were in patients aged 3 to 65 years. Among these patients, 52 (6%)
      did not meet any exclusion criteria and were classified as potential kidney
      donors. Of these 52 patients, eight (1%) were classified as very suitable donors,
      defined as no diabetes mellitus, no hypertension, good renal function (serum
      creatinine < 1.3 mg/dL), age less than 50 years, and death in the intensive care
      unit or emergency service. Twenty-five of the remaining 44 sub-optimal potential
      donors who did not meet the criteria of very suitable were classified as having
      high potential to be donors by a combined scoring system (sum score = 5-6). The
      results suggest that there is a considerable number of potential NHB kidney
      donors in Taiwan. Programs to advocate use of NHB kidney donors and education of
      the public and transplant professionals might significantly increase the number
      of kidneys available for transplantation in Taiwan.

PMID- 12189655
TI  - Media medicine.

PMID- 12189654
TI  - Internuclear ophthalmoplegia associated with transient torsional nystagmus.
AB  - The association of internuclear ophthalmoplegia (INO) with torsional nystagmus is
      rare. We report the case of a 63-year-old man presenting with sudden onset of
      diplopia. On ocular examination, he had left INO and a torsional nystagmus with
      counter-clockwise quick-phases from the patient's point of view in the primary
      position, ipsiversive to the side of the medical longitudinal fasciculus (MLF)
      lesion at the pontomesencephalic junction on magnetic resonance images. Neither
      skew deviation nor head tilting was noted at that time. Two days later, the
      torsional nystagmus disappeared, although the limitation of adduction in the left
      eye remained. We speculate that with sparing of the rostral interstitial nucleus
      of the MLF, a small lesion in the MLF may involve the ipsilateral vertical
      integrator, the interstitial nucleus of Cajal, producing an INO associated with a
      transient ipsiversive torsional nystagmus.

PMID- 12189656
TI  - Antiherpes zoster treatment.

PMID- 12189657
TI  - Alison's homemade keratolytic.

PMID- 12189658
TI  - Childhood ENT disorders. When to refer to specialists.
AB  - BACKGROUND: Ear, nose and throat (ENT) are among the commonest reasons for
      attendance in general practice. Acute problems are managed by the general
      practitioner, but chronic and recurrent conditions are often referred for
      surgical intervention. Tonsillectomy and insertion of tympanostomy tubes are two
      of the most frequently performed paediatric surgical procedures in Australia yet
      rates of admission vary across geographic areas and socioeconomic strata.
      Referral patterns and criteria for surgery vary widely. OBJECTIVE: This article
      reviews the natural history of some common childhood ENT conditions and the
      evidence of effectiveness of traditional surgical interventions in order to
      address the question: 'When should GPs refer to an ENT surgeon (or conversely,
      when should they not refer)?' DISCUSSION: Recurrent and chronic ear and throat
      conditions in children will usually resolve spontaneously. There is no good
      evidence of long term benefit from surgical interventions for several common ENT
      conditions. General practitioners need to weigh up the disadvantages and risks of
      the surgery with the likely benefit to the individual patient.

PMID- 12189659
TI  - A hole in the drum. An overview of tympanic membrane perforations.
AB  - BACKGROUND: Tympanic membrane perforations are common and can be categorised into
      either acute or chronic. Acute perforations are usually traumatic or inflammatory
      in origin and heal spontaneously. Chronic perforations may be associated with
      underlying progressive disease. OBJECTIVE: To differentiate between safe and
      unsafe perforations and describe management principles for these conditions.
      DISCUSSION: The majority of acute tympanic membrane perforations heal
      spontaneously. Those that do not can be considered for surgical repair. Chronic
      perforations should be viewed as either safe or unsafe depending on the risk of
      progression to significant complications. Unsafe perforations are often
      associated with cholesteatoma (an epidermoid cyst of the middle ear and mastoid
      air cell system). Cholesteatoma destroys bone and causes serious ear and
      intracranial complications--surgery is commonly required.

PMID- 12189660
TI  - Tinnitus. More can be done than most GPs think.
AB  - BACKGROUND: Tinnitus is the appreciation of sound arising from an internal
      source. The sound may be pulsating and arising from a vascular cord near the ear
      or it may arise from pathology in the inner ear. When pathology in the inner ear
      is the cause of the tinnitus, the tinnitus is nonpulsating, continuous and may
      have variable frequencies and intensity. OBJECTIVE: This article aims to outline
      the diagnostic features of tinnitus to determine causes and aggravators, and
      provide an overview of treatment. DISCUSSION: Assessment of tinnitus involves
      distinguishing objective from nonobjective tinnitus, pulsatile from nonpulsatile
      tinnitus and the investigation of features that will determine the cause of
      tinnitus and any aggravating factors. Management of the condition involves the
      treatment of the underlying cause, attention to any contributing aggravators and
      the control of symptoms.

PMID- 12189661
TI  - Management of epistaxis in general practice.
AB  - BACKGROUND: The vast majority of cases of epistaxis can be managed successfully
      within general practice. OBJECTIVE: To describe a range of clinical interventions
      in the management of epistaxis appropriate to general practice. DISCUSSION: A
      number of relatively simple treatments and procedures may provide relief for
      anterior nasal bleeding, which is the site for over 80% of cases of epistaxis.
      Where more procedural interventions are necessary, adequate preparation and
      appropriate tools are required to perform these processes safely. Initial
      identification of the site of bleeding before commencement of treatment may be
      difficult but allows the correct treatment to be applied with minimal discomfort
      to the patient. More copious bleeding which constitutes less than 5-10% of cases,
      is usually the result of posterior nasal bleeding and is best treated in a
      facility well set up to handle such an eventuality. In cases of chronic
      epistaxis, a number of interventions, medical and surgical have been trialled
      with variable success, and should be used with caution in general practice.

PMID- 12189662
TI  - Assessment of the dizzy patient.
AB  - BACKGROUND: Dizziness is a very common complaint in the community, especially
      among the elderly. The lack of objective measures of the condition can create
      difficulties in diagnosis and management. OBJECTIVE: This article aims to provide
      a framework for the assessment of the patient presenting with dizziness. The
      framework will provide a systematic means of obtaining a diagnosis and
      formulating a management plan. DISCUSSION: Despite the high prevalence of
      dizziness in the community many patients continue to have symptoms that are
      inadequately controlled. A systematic approach in the assessment of these
      patients, in particular a thorough history and examination will often provide a
      clear direction as to the diagnosis and most appropriate management.

PMID- 12189663
TI  - Test your knowledge. Increasing hearing loss.

PMID- 12189664
TI  - HRT advice. Information for specific scenarios.

PMID- 12189665
TI  - Reading systematic reviews.
AB  - BACKGROUND: While systematic reviews should be of assistance in decision making,
      currently many reviews are unreliable, poorly reported or not clinically useful.
      It is therefore important that they are read critically. OBJECTIVES: The
      objective is to provide a logical way to appraise systematic reviews. Particular
      objectives are to demonstrate how to use a validated general guide for appraising
      systematic reviews; amend the guide so that it can be used to appraise systematic
      reviews of controlled trials, prognostic studies and studies evaluating
      diagnostic tests; choose between discordant reviews and assess the usefulness of
      good systematic reviews. DISCUSSION: Guidelines for undertaking and reporting
      systematic reviews should eventually improve their quality and usefulness. In the
      meantime, reviews must be appraised critically, particularly those outside the
      Cochrane Library.

PMID- 12189666
TI  - One pair must last a lifetime. Foot care in diabetes.

PMID- 12189667
TI  - Guidelines for everyday foot management.

PMID- 12189668
TI  - Inhaled steroids in asthma. Should the doses be reduced?
AB  - BACKGROUND: Since their introduction in the 1970s, unit doses of inhaled
      corticosteroids (ICS) have increased exponentially (a twenty-fold rise from
      beclomethasone 50 micrograms through fluticasone 500 micrograms). Current
      prescription data suggests that in Australia more than 50% of all dispensed
      fluticasone/salmeterol dry powder units are the 500/50 micrograms combination.
      OBJECTIVE: To discuss the efficiency of doses currently used in Australia.
      DISCUSSION: The use of both single drug ICS therapy alone or in conjunction with
      a long acting beta agonist (LABA) may be too high. The additional therapeutic
      effects of such doses are likely to be of minimal benefit (if any at all) and
      expose patients to unnecessary long term side effects.

PMID- 12189669
TI  - New treatment for Meniere's disease.

PMID- 12189670
TI  - Osteoporosis detection in the community. Are patients adequately managed?
AB  - In conclusion, osteoporosis remains underdiagnosed in the South Eastern Sydney
      area. A public awareness campaign, highlighting the need for bone densitometry in
      men and women 45 years and older who sustain minimal trauma fractures in order to
      diagnose osteoporosis, is required. Proven therapies for patients presenting with
      osteoporotic fractures, including men, are now available and should be
      considered.

PMID- 12189671
TI  - Test your knowledge. Loin pain.

PMID- 12189672
TI  - Medication errors. Iron injections.

PMID- 12189673
TI  - Does living better also mean living longer? Quality of life and cancer.

PMID- 12189674
TI  - Health outcomes in people with type 2 diabetes. A record linkage study.
AB  - INTRODUCTION: This study pilots a method of measuring health outcomes in a
      general practice population of patients with type 2 diabetes. METHOD: The
      Diabetic Register of the Perth and Osborne Divisions of General Practice was
      linked to the Western Australian Health Services Research Linked Database.
      RESULTS: Of the 487 patients in the study, 332 (68%) had been admitted before
      their diagnosis of diabetes (40% with a diabetes related condition), and 56% were
      admitted postdiagnosis (55% with a diabetes related condition). The admission
      rate increased with age and duration of diabetes. DISCUSSION: The data show that
      a large proportion of diabetic patients suffer from serious comorbidity both pre-
      and post-diagnosis and demonstrate that their hospital admission rate is higher
      than that in the general population. CONCLUSION: The project demonstrates that
      linked hospital morbidity data can be used to monitor health outcomes in a
      general practice population of diabetic patients.

PMID- 12189676
TI  - Keeping our GPs healthy. An overview of current Australian initiatives to address
      GP wellbeing.

PMID- 12189675
TI  - Screening for chlamydia in general practice.
AB  - OBJECTIVE: To determine the prevalence of genital Chlamydia trachomatis infection
      in young patients presenting to general practitioners and to evaluate selective
      screening, based on risk factors, including gender. METHODS: A cross sectional
      survey of 508 consecutive patients aged 18-24, presenting to six general
      practices and one youth clinic in Mackay, North Queensland. We screened urine for
      chlamydia using Ligase chain reaction. RESULTS: Of 508 samples, 25 were positive
      (5%). The only factors with increased risks of infection were attendance at a
      youth clinic and recent change in sexual partner. It was as high in men as in
      women. CONCLUSION: Prevalence of chlamydia infection may be high enough to
      support screening of all patients aged 18-24, depending on cost effectiveness
      studies.

PMID- 12189677
TI  - [Stroke management: general recommendations].

PMID- 12189678
TI  - [Physical therapy in stroke rehabilitation].

PMID- 12189679
TI  - [Neuropsychological rehabilitation in stroke].

PMID- 12189680
TI  - [Pharmacology in recovery after stroke].

PMID- 12189681
TI  - [European Stroke Initiative: stroke management].

PMID- 12189682
TI  - [Stem cells--potential therapeutic use in neurological diseases].
AB  - There is a growing interest in medical potential of stem cells which may be used
      someday to create new tissue. Suggested applications involve a board spectrum
      ranging from the replacement for cells destroyed by diseases to even organ
      transplants. As ethical and legal controversy makes uncertain the future of
      embryonic stem cells research, attention has been recently turned to adult stem
      cells to discover whether they also can serve to transplantation. In this article
      we present data indicating that adult stem cells found in areas of the body like
      blood, skin, lymph and nervous systems, may be more versatile than previously
      assumed and in certain conditions can broke tissue barriers for differentiation.
      Thus, in this respect they can behave like their own pluripotent ancestors,
      although underlying mechanisms for this phenomena are still not clear.
      Furthermore, the following issues are shortly discussed: What are the
      characteristics of the different stem cells and where they can be found. What are
      experimental evidences that stem cells can be used for brain repair. What are the
      main problems must be solved before their clinical application and the risk
      benefit assessment. The possible strategies and targets for stem cell therapies
      of neurological diseases.

PMID- 12189683
TI  - [Introduction to neuronal plasticity].
AB  - Neuronal plasticity is observed throughout animal kingdom. It underlies processes
      of functional restoration after brain injury or peripheral deafferentation and it
      also makes learning and memory possible. The paper reviews briefly the conditions
      which, according to Hebb's rule, are required for neuronal plasticity to occur.
      It stresses the importance of convergence of signals, coincidence and repetition.
      The roles of NMDA receptors and neuromodulators are described. The paper reviews
      current concepts and data concerning anatomical changes that accompany plasticity
      of cortical representations.

PMID- 12189684
TI  - [Aims of neurorehabilitation].
AB  - The aim of this article is to present basic problems of new neuro-rehabilitation,
      its purposes and methods. This paper shows the newest methods of kinezytherapy
      and drugs used in improving the rehabilitation process. Authors present
      interdisciplinary rehabilitation teams dealing with neurologically disabled
      patients. They also show short programs of rehabilitation in multiple sclerosis
      and in stroke patients. That diseases are very popular in main population and are
      one of the main cause of disability in adult people.

PMID- 12189685
TI  - [Neurological rehabilitation from the perspective of brain plasticity].
AB  - A clinical aspect of neuropsychological rehabilitation from the perspective of
      brain plasticity is presented. The main principles of guided recovery of
      cognitive functions are discussed. Some recommendations for practical therapy of
      brain-injured patients with cognitive impairments are made.

PMID- 12189686
TI  - [Clinical effects of intensive physiotherapy in stroke patients].
AB  - The present therapies used for post stroke patients are often not effective. Many
      patients finish the therapy and are not able to function independently. This
      situation is not in line with the present level of neurobiology: which states
      that function after focal lesion of C.N.S. can be recovered. Recently many
      studies have been undertaken which indicate the possibility of cortical
      plasticity by intensive physiotherapy. The main aims of the study were to review
      the efficacy and application of Constraint Induced Therapy for post stroke
      patients in a neurological rehabilitation ward and outpatient clinic. The group
      was selected from the patients who were admitted into the clinic. The patients
      signed the agreement that they could walk unaided and their affected arm could
      use a primitive grip. The patient's unaffected arm was restrained using a sling
      for 5 hours per day for 15 consecutive days. Also each patient had one hour per
      day of physiotherapy based on PNF and NDT Bobath concepts. Patients were tested
      before and after the experiment using functional tests (modified Wolf Test) and
      testing of motor deficit using Tests for the Quality of Movement Patterns (by
      Bobath). Seven patients were selected with an average time from stroke of 11
      months. The average age was 46 years. All patients completed the study without
      any adverse affects. All patients increased their functional ability and
      decreased the motor deficit of the affected arm. The average increase in task
      function was 27%. The greatest average improvement (40%) was noted in chronic
      patients who suffered from stroke more than 6 months previous. The experiment was
      completed without any major reorganisation of the neurological ward and without
      additional expenditure. The small group of patients that participated in this
      study indicates that this CI therapy should be utilised for a larger amount of
      patients with greater neurological deficits.

PMID- 12189687
TI  - [Current strategies in peripheral nerve repair].
AB  - The paper presents main research trends focused on peripheral nerves
      regeneration. Modern surgery techniques in humans require dissection of the nerve
      bridges, leading to extra mutilation of a patient. The recovery of motor and
      sensory functions is also unsatisfactory. Therefore scientists are looking for
      new materials and techniques capable of replacing injured nerve trunks as well as
      of improving the reinnervation of target tissues. In this kind of experiments
      chambers joining proximal and distal stumps of transected peripheral nerve are
      very useful. Such chambers may also contain growth-promoting factors or glial
      cells supporting the regrowth. Progress in molecular biology and biomaterials
      engineering will be probably the most critical step to therapeutic intervention
      in nerve regeneration.

PMID- 12189688
TI  - [Transplants as a therapy after spinal cord injury].
AB  - This review describes shortly phenomena that take place in different parts of
      central nervous system (CNS) after the spinal cord injury: 1/ due to axotomy many
      of neurones present outside the cavity of lesion (even those of supraspinal
      origin) can atrophy or die as an effect of necrosis or apoptosis; 2/ at the
      injury site itself, the primary and secondary effects lead to increased cell loss
      and the scar or cyst formation that are the mechanical barrier for regenerating
      axons; 3/ due to abolished conduction across the injury site the spinal cord
      circuitry below the lesion is deprived of supraspinal inputs. Then this review
      presents the new therapeutic strategies that were developed recently to obtain at
      least partial recovery of motor functions after spinal cord injury. The cell body
      can be rescued by applying various factors that increase intrinsic neural repair
      (e.g. neurotrophins or anti-apoptotic agents). To enhance the axonal regrowth
      through the lesion cavity, the scar and cyst formation can be reduced by
      constructing the bridges using e.g. the Schwann cells, fetal tissue, stem cells,
      olfactory ensheating glial cells, or by application of macrophages. To induce
      partial restoration of some functions that are controlled by neural circuitry
      below the lesion the various methods for enhancing the plasticity in segmental
      circuitry were developed (e.g. rehabilitation by locomotor training or
      intraspinal transplantation of monoaminergic cells). As a consequence of the
      great unpredictability of effects obtained after injury at different parts of the
      spinal cord the various strategies for repair need to be coordinated for optimal
      recovery.

PMID- 12189689
TI  - [Can neurotrophins help to repair an injured spinal cord?].
AB  - Basic information about neurotrophins, their receptors and distribution of these
      proteins in the central nervous system as well as their role in the development
      and maturity of the nervous system will be briefly reviewed in this chapter.
      Special emphasis will be given to the role of neurotrophins and their receptors
      after the damage of the nervous system. Finally, our recent data showing a
      possibility of increasing of endogenous pool of BDNF and NT-4 as well as their
      TrkB receptor in the spinal cord due to long-lasting, moderate locomotor training
      will be presented and discussed in terms of its clinical applicability.

PMID- 12189690
TI  - Cholera, 2001.

PMID- 12189691
TI  - Criteria used in compiling the infected area list.

PMID- 12189692
TI  - [Application of Mckissock reduction mammaplasty technique in treatment of giant
      breast tumor].
AB  - OBJECTIVE: To obtain postoperative desirable appearance of the deformed breast we
      apply Mckissock reduction mammaplasty technique in treatment of giant benign
      breast tumor. METHODS: According to the principle of Mckissock reduction
      mammaplasty technique, we design a special incision to remove the tumor in
      company with the proceeding of mammaplasty. RESULTS: 11 cases of operation with
      satisfactory results for giant benign tumors have been performed since 1993.
      CONCLUSIONS: Standard reduction mammaplasty technique has turned out to be an
      effective remedy for giant tumor spoiling the appearance of the breast.

PMID- 12189693
TI  - [The applications of the dermal vault technique in mammaplasty].
AB  - OBJECTIVE: To search for the applications of the dermal vault in mammaplasty.
      METHODS: The dermal vault was planned as large as possible according to the
      degree of the macromastia and mammaptosis. The residual gland was sculptured and
      fixed with the dermal vault in order to reconstruct the protrude, pliable and
      living breasts. RESULTS: The 27 cases (53 breast) were performed with this
      technique. The result is satisfactory and there are no complications. CONCLUSION:
      It is a good method to use the dermal vault as a sculpturing and fixing material
      in mammaplasty. The breasts formed are projecting, pliable and moveable. The scar
      is not apparent and the result is persistent.

PMID- 12189694
TI  - [Treatment of capsular contracture through areolar incision after augmentation
      mammaplasty].
AB  - OBJECTIVE: To explore the treatment of breast sclerosis caused by capsular
      contracture after augmentation mammaplasty, and preventive measures after the
      treatment to avoid the recurrence. METHODS: With the incision through periareola,
      a part of the fibrous capsule and fibrillate tissue which is between the base of
      the capsula and the wall of the capsula were resected in the shape of wedge. At
      the same time, the wall of the capsular cavity was incised in radiant shape to
      relax it. After operation, the early and effective massage should be fully used.
      RESULTS: 17 case of 26 case were given follow-up over half a year, the results
      were satisfactory. CONCLUSIONS: After capsular contracture was relaxed and a part
      of the fibrous capsula between the base and the wall of the capsular cavity was
      resected in the shape of wedge, the prosthesis can be moved smoothly in the
      suitable cavity without any obstruction. In addition to the early and effective
      massage after operation, the methods might reach the ideal results.

PMID- 12189695
TI  - [Clinical study of the hemodynamics of both ends (proximal and distal) of
      internal mammary artery and its following-up].
AB  - OBJECTIVE: To verify the value of retrograde flow of Internal Mammary Artery
      (IMA) used as one of the supplying arteries and to develop a new method of
      applying IMA in breast reconstruction. METHODS: During breast reconstruction with
      free bilateral transverse rectus abdominis myocutaneous (TRAM) flap, the
      pressures and velocities of the two ends (proximal and distal) of internal
      mammary artery as well as the according perfusion unit (PU) of TRAM were measured
      in two patients who suffered from mammectomy because of carcinoma. RESULTS: The
      pressure at distal end was 66 or/and 58 mmHg, the pressure at proximal end was 88
      or/and 75 mmHg, the former is 75%-77% of the later. The immediate rate of blood
      flow of distal anastomotic stoma was 74 or/and 52 ml/min, that of proximal was 94
      or/and 70 ml/min, the former is 74%-78% of the later after anastomosed to the two
      sides of deep inferior epigastric arteries (DIEA) separately. Under condition
      that both ends (proximal and distal) of IMA contributing as the supplying blood
      vessels simultaneously, the PU of TRAM was the best. The rates of blood flow at
      the two anastomotic stomas are similar to each other in late stage (evaluated at
      the fifth year follow-up). CONCLUSION: The distal end of internal mammary artery
      can supply blood flow in a considerable level, similar with the proximal end.

PMID- 12189696
TI  - [The histological study of the capsules formed around the mammary prosthesis].
AB  - OBJECTIVE: To observe and analyze the pathohistological characteristics of
      capsules which formed around the mammary prosthesis with different contents. And
      to provide the selective basis for ideal and safe prosthesis in clinical
      practice. METHODS: 20 specimen of the capsules were taken from 20 cases who
      receive the operation of prothesis removal for different reasons. HE, Masson and
      Mallory staining were used to analyse the tissue structure and characteristics
      under the light microscope. RESULTS: The common structure including the collagen
      fibers accumulation, inflammatory cells infiltration and the capillary
      hyperplasia were found in all specimen. A layer of squamous epithelium-like cell
      was detected in some specimen. The specific characteristics were also found in
      different capsules formed around different prosthesis. In the capsules around
      vegetable oil prosthesis, there was excessive collagen fiber accumulation, and
      the capsules were much thicker. In the PVP (polyvinylpyrolidone) prosthesis
      capsules, there was severe inflammatory cell infiltration, and the number of
      eosinophilic granulocyte increased obviously. In the silicone gel and saline
      prosthesis capsule, the collagen fibers were well-arranged and the inflammatory
      cells were much less. Synovial metaplasia was detected in two cases. CONCLUSION:
      1. The capsules form around the prosthesis in all cases after mammary
      augmentation. 2. There will be synovial metaplasis in some cases, for vegetable
      oil prosthesis, the collagen over-accumulated which lead the capsules become
      thicker and harder. So it is not a kind of ideal mammary prothesis. 4. The severe
      infiltration of the inflammatory cells especially the large quantity of
      eosinophilic granulocyte indicate the possibility of the delayed hypersensitive
      reaction mediated by eosinophilic granulocyte. Cautious attitude should be taken
      during application.

PMID- 12189697
TI  - [Using of shadow-picture ultrasonography in the following-up of breast bulging
      operation].
AB  - OBJECTIVE: To investigate the significance of using high-frequency 2-dimonsional
      ultrasonography and color Doppler ultrasonography in the following-up of breast
      bulging operation. METHODS: 7-11 MHz high-frequency 2-dimonsional ultrasonography
      and color Doppler ultrasonography were used on 18 patients, whose one or two
      breasts had abnormal symptom after breast bulging operation. RESULTS: Implants or
      blood swelling which took on a bag have no or low echo district, its margin is
      clear, regular and has a clear boundary line with the tissue around breast. The
      breaking and oozing, outing, moving, infection of implants, blood swelling, and
      sclerosis of wrapping membrane after breast bulging operation have special 2
      dimonsional voice picture and the tissue around it has more or less color blood
      picture and Doppler frequency expression. CONCLUSION: Technique of shadow-picture
      Ultrasonography has great diagnose value and clinical significance in the
      detection of complications after breast bulging operation.

PMID- 12189698
TI  - [Repair of the facial tissue defects with reversed narrow pedicle lateral
      maxillocervical fasciocutaneous flap].
AB  - OBJECTIVE: To introduce a method of repairing facial tissue defects caused by
      various factors. METHODS: The reverse narrow pedicle lateral maxillocervical
      fasciocutaneous flap was designed with its pedicle located in front of auricle.
      The size of the flaps ranged from 5 cm x 6 cm to 10 cm x 11 cm. The length and
      width of the pedicle ranged 2 cm-5 cm and 1 cm-1.5 cm. RESULTS: This
      fasciocutaneous flap was used in 21 cases. All flaps survived except 1 flap
      showing distal skin necrosis. CONCLUSION: This fasciocutaneous flap didn't
      include any major blood vessel. The ratio of the pedicle width to flap length
      broke that of traditional flap and was reverse transfer. The transposition of the
      narrow pedicle flap was easy. The postoperative appearance (color, texture,
      cosmetic aspect) was satisfactory. This method was a new design and was ideal for
      large facial tissue defect repair.

PMID- 12189699
TI  - [The dorsal fasciocutaneous island flap of the finger for the repair of volar
      skin defects of the same finger].
AB  - OBJECTIVE: To evaluate a new fasciocutaneous island flap for the repair of volar
      skin defects of the same finger. METHODS: A fasciocutaneous island flap, 0.5 cm
      distal to the volar skin defect, was formed on the dorsal side of the same
      finger. The proximal fascial pedicle was dissected long enough so that the flap
      could be transposed to the volar wound freely. One dorsal vein was kept
      undisturbed to safeguard the venous drainage of the distal part of the finger.
      When the side of the flap was so big that bilateral dorsal veins were included
      within the flap, the non-pedicle side of the flap was elevated first superior to
      the fascia until the dorsal vein was excluded from the flap, and the rest of the
      flap was dissected deep to the fascia. The donor side of the flap was covered
      with split skin graft. RESULTS: Six cases were treated. All flaps survived well.
      CONCLUSION: The dorsal fasciocutaneous island flap of the finger can be used
      safely for the repair of volar skin defect of the same finger.

PMID- 12189700
TI  - [Free pulp flap of toe in repairing thee pulp defect of finger].
AB  - OBJECTIVE: To investigate a method in repairing pulp defects of thumb and finger.
      METHODS: To examine and analyze 19 case of pulp defect of thumb and finger
      repaired with free pulp flap of toe since 1987. RESULTS: All the transplanted
      pulp flaps in 19 cases are survived and are followed up from 3 months to 12
      years. All the digits recovered good out appearance with normal skin creases and
      ridges. The two-point discriminations are 6-8 mm. The repaired thumb or finger
      are free of paint during pinching and grasping. The split thickness skin grafts
      on the donor toes yield no hypertrophic scar and no callousity occurred on the
      donor feet. No detrimental influence occurred on the donor feet. CONCLUSION: The
      free pulp flap transfer has obvious advantages than any other methods in
      repairing pulp defects of single finger by, first, good outward appearance,
      second, quality of the skin over donor flap is almost as rub resistant as
      recipient finger, third, anastomosis of the digital nerves give functional
      influence, finally, short rehabilitation period however, the operation requires
      microsurgical technique and has a risk of failure.

PMID- 12189701
TI  - [A study of the pour blood and the oxygen metabolic in tissue for extra-artery
      fascia flap].
AB  - OBJECTIVE: The aim of the work was to study the change for blood pour into the
      artery fascial flap and oxygen metabolic in tissue that knew the process of the
      flap. METHODS: We do the artery fascial flap in the rabbit, then measured the
      skin capillary blood flow and the content of the MDA. RESULTS: The content of the
      MDA rise when the blood flow descends in the flap, but it lives well.
      CONCLUSIONS: That the content of the MDA rise as time the blood flow descend in
      the flap is a gradual process of the whole flap from tip to end, the flap will
      not appear necrosis until the MDA reach a rather degree.

PMID- 12189702
TI  - [Subcutaneous injection of plasmid VEGF gene: a method of gene therapy to enhance
      the viability of random skin flap].
AB  - OBJECTIVE: Gene therapy has been becoming one of the most attractive medical
      areas. But the using of gene therapy in plastic surgery is relatively scarce. Our
      purpose was to investigate the effect of naked plasmid encoding Vascular
      Endothelial Growth Factor on the viability of the random skin flap by directly
      injected subcutaneously. METHODS: 30 female Sprague-Dawley rats randomly divided
      into three groups. A random dorsal skin flap of 3 cm x 9 cm was elevated in each
      of the rats. And 1 ml double-distilled water solution was injected
      subcutaneously, which was only water in group 1 during the operation, 200
      micrograms VEGF cDNA plasmid in group 2 during the operation, 200 micrograms
      pcDNA3.1/zeo(+)--VEGF in group 3, 24 hours before the operation, respectively. 7
      days after the operation, all the animals were sacrificed by overdose anesthetic.
      The survival tissue was measured with planimetry. Two samples were harvested from
      each group for pathological check and immunohistochemical test. RESULTS:
      Immunohistochemical staining demonstrated that there was human VEGF deposited
      around the capillary in the flaps treated with VEGF gene. The flaps treated with
      VEGF gene had a larger percentage of survival skin (group 1 = 47% +/- 5.4%, group
      2 = 65.4% +/- 6.3%, group 3 = 72.3% +/- 8.5%, P < 0.05). CONCLUSION: VEGF gene
      directly injected into subcutaneous can express VEGF. It makes the gene therapy
      simple and practical and will be promising future in the tissue transplantation.

PMID- 12189703
TI  - [The inhibitory effect of tamoxifen on human dermal fibroblast-populated collagen
      lattices].
AB  - OBJECTIVE: To investigate the potential therapeutic effect of tamoxifen in
      treating abnormal skin scar contraction. METHODS: Fibroblast-populated collagen
      lattices, which were made by embedding human dermal fibroblasts within type I
      collagen forming a three-dimensional culture system, were used as an invitro
      model. Then media either without or with addition of tamoxifen from 1 mumol/L to
      50 mumol/L were added to the collagen lattices. Lattice areas were measured at
      intervals to assess the influence of tamoxifen on the lattice contraction. To
      visualize changes in the morphology and vitality of fibroblasts, MTT was added to
      the lattices. RESULTS: Tamoxifen had an inhibitory effect on lattice contraction
      by a dose- and time-dependent pattern. 5 mumol/L or less of tamoxifen didn't show
      any influence on lattice contraction but 30 mumol/L or higher completely
      inhibited contraction. At intermediate concentrations from 10 mumol/L to 20
      mumol/L the degree of lattice contraction was dose- and time-dependent, which was
      demonstrated by the reversibility of inhibition. Both the inhibition of
      contraction and the reversibility of inhibition appeared to correlate with
      changes in fibroblast morphology. CONCLUSION: Tamoxifen could inhibit the
      contraction of fibroblast-populated collagen lattices, indicating that tamoxifen
      may have potential effect on abnormal scar contraction in vivo.

PMID- 12189704
TI  - [Effects of microfilaments on the expression of collagenases and tissue inhibitor
      of metalloproteinases-1 in fibroblasts].
AB  - OBJECTIVE: To investigate the roles of microfilaments in the expression of
      collagenase and TIMP-1 in normal and hypertrophic scar. METHODS: Cell culture and
      Northern blot hybridization methods were used in this study. RESULTS: After the
      disruption of microfilaments with cytochalasin B, mRNA contents of collagenase
      and TIMP-1 both increased significantly in normal and hypertrophic scar
      fibroblasts. CONCLUSION: The result suggest that the microfilament cytoskeleton
      may regulate the synthesis and degradation of ECM, which may be a mechanism of
      gene regulation during wound healing.

PMID- 12189705
TI  - [Experimental study of the expression of c-myc, c-fos and proto-oncogenes on
      hypertrophic and scars].
AB  - OBJECTIVE: To investigate the correlation between the expression of key proto
      oncogenes playing major roles in tumorigenic process and abnormal sarring.
      METHODS: Immunohistochemical technique was performed to detect the expressions of
      c-myc, c-fos and ras p21 proteins on hypertrophic scars, keloids and normal skin.
      Image analysis was used to compare their quantitative difference of expression.
      RESULTS: C-myc and c-fos expressions on the nucleus of fibroblasts of
      hypertrophic and keloid scars were significantly higher than normal skin
      controls, and there was no difference between the two lesions. Ras p21 expression
      was not detected on the fibroblasts of hypertrophic and keloid scars. CONCLUSION:
      1. c-myc and c-fos oncogenes are activated on hypertrophic and keloid scars,
      which may contribute to proliferation and differentiation of fibroblasts,
      synthesis and degradation of collagen and regulation of cytokines and induce
      abnormal scarring, the mechanisms of their effects remain to be further studied.
      2. Ras gene may not mutate or its mutations may not play a major role in the
      process of abnormal scarring. 3. Only part of proto-oncogenes moderately
      expressed on abnormal scars. The expression of multiple oncogenes does not
      coexist in abnormal scars may be the cause of their less chances to induce
      malignant transformation.

PMID- 12189706
TI  - [The treatment of ectropion following lower eyelid blepharoplasty with tissue
      expander in infra-orbital region].
AB  - OBJECTIVE: To introduce a new method to correct ectropion following lower eyelid
      blepharoplasty. METHODS: To expand the skin and tissue in the infra-orbital
      region of ectropion following lower eyelid blepharoplasty by using an expander
      (30-50 ml) from oral vestibulum. After 1-2 weeks, the ectropion could be
      corrected. RESULTS: 32 cases were all successful by using this methods.
      CONCLUSION: It is a effective method expanding the skin and tissue in infra
      orbital region by tissue expander to correct the ectropion following lower eyelid
      blepharoplasty.

PMID- 12189707
TI  - [Anatomical division and electromyographic assessment within latissimus dorsi].
AB  - OBJECTIVE: To evaluate the anatomical division within latissimus dorsi and its
      electromyographic change as shoulder articulation movement. METHODS: Using
      anatomical observation, projection of trophic vessel and nerve of latissimus
      dorsi was marked in the surface of skin. Electromyographic assessment of
      different area of latissimus dorsi was measured. RESULTS: The latissimus dorsi
      was mainly supplied by thoracodorsal and its interior and external branches. The
      latissimus dorsi can be divided three area based on these anatomical result.
      Electromyographic amplitude in the three areas of muscle are different.
      CONCLUSION: Lastissimus dorsi can be divided into three areas by thoracodorsal
      vessel and nerve. The third area fibres were utilized preferentially when
      subjects performed six kinds of movements of the shoulder joint.

PMID- 12189708
TI  - [Investigation on contraction mechanism of expanded tissue].
AB  - OBJECTIVE: To investigate the contraction mechanism of expanded tissue. METHODS:
      White domestic pigs were employed to establish tissue expansion model. Tissue
      samples were taken after expansion for contraction measurements and
      histopathological observation. RESULTS: Dermis and capsule were the main
      positions of contraction. In the dermal layer, elastic fibers and myofibroblasts
      proliferated greatly and alpha-Actin enhanced in the myoepidermal cells and
      capillary endothelial cells during expansion. In the capsule, the direction of
      elastic and collagen fibers arranged crossly and formed into special contractible
      structure. CONCLUSION: Elastic fibers, myofibroblasts and alpha-Actin enhancement
      of cells were the substantial materials of tissue contracture increases. The
      results suggest that suitable tension must be applied into expanded flaps for
      anti-contraction.

PMID- 12189709
TI  - [Long-term changes after transplantation of expanded skin in dogs].
AB  - OBJECTIVE: To investigate the long-term changes of expanded skin after
      transplantation. METHODS: The expanded skin in dogs at 0 week, 3 weeks, 6 weeks,
      3 months and 6 months after transplantation was observed through areas,
      histomorphological, electron microscopic, collagen content, biomechanical, and
      immunohistochemical methods. RESULTS: The expanded skin was close to the control
      groups in all observations. CONCLUSION: The biological changes after expansion
      remain in 3 months. The expanded skin will gradually recover to normal in 3-6
      months. It is similar to a wound repair process.

PMID- 12189710
TI  - [Correction of cleft lip nose deformities using Ni-Ti shape memory alloy mesh
      stent implant].
AB  - OBJECTIVE: To demonstrate the feasibility of Ni-Ti shape memory alloy mesh stent
      for the correction of nasal deformities caused by cleft lip. METHODS: Six
      patients with cleft lip-nose deformities, aged from 18 to 32, were treated by
      implantation of Ni-Ti shape memory alloy mesh stent through intra-nasal
      incisions. RESULTS: The symmetry of the alar and nasal tip were cosmetically
      acceptable. Satisfactory relationship between the lip and the nose were obtained
      in all the patients. There were not any postoperative surgical complications by 6
      to 12 months' follow-up. CONCLUSION: The Ni-Ti shape memory alloy mesh stent is
      suitable for use in the correction of adult cleft-lip nose deformities.

PMID- 12189711
TI  - [Reconstruction of the external ear utilizing expanded scarred skin flap].
AB  - OBJECTIVE: To investigate the feasibility of ear reconstruction using local
      expanded scarred skin flap. METHOD: We used local postauricular expanded scar
      skin flaps to reconstruct external ear in 24 patients. RESULTS: Of these cases,
      22 flaps survived completely. In 2 patients, the cartilage framework exposed over
      the upper pole of helix region because of undue tension in suturing the tissue
      edges. One year's follow-up revealed satisfactory results. CONCLUSION: Using the
      expanded scarred skin flap for ear reconstruction is practical and effective,
      when there's no normal skin available in the local area.

PMID- 12189712
TI  - A review of the legal and ethical issues for the conduct of HIV-related research
      in prisons.
AB  - This article sets the stage for future discussions of expanding prisoners' access
      to clinical trials in an effort to move from commentary and recommendations to
      changes in practice. It describes barriers to access to clinical trials, the
      demographics of HIV/AIDS in prisons, the unique situation posed by the potential
      for HIV-related research in prisons, and examines briefly the history of prisoner
      research in the U.S. The article considers both ethical and legal responses to
      clinical trials in prisons, noting the potential for and limitations of legal
      actions. Finally, it makes recommendations for conditions necessary to conduct
      ethical research in prisons and calls for more cooperation between prison systems
      and HIV/AIDS clinical trials researchers to make expanded access to clinical
      trials a reality.

PMID- 12189713
TI  - Racial differences in end-of-life care for patients with AIDS.
AB  - This study examines the place of death for persons with AIDS, and the adequacy of
      the pain treatment that they received in their final months of life. Variations
      in the use of pain treatment during three months before death and place of death
      by patient's characteristics such as gender, race/ethnicity, mode of
      transmission, and geographical location are examined. We used merged AIDS
      surveillance data and paid Medicaid claims data for the period between 1991 and
      1998 to examine the outcomes. Multivariate analysis was done using logistic
      regressions. Overall, approximately half of the sample received an outpatient
      prescription for analgesics during the last three months of life. A majority of
      the decedents (62 percent) died in a hospital. Significant differences in pain
      treatment and place of death existed between members of racial minority groups
      and Whites. Higher rates of pain treatment and lower likelihood of dying in a
      hospital were noted among beneficiaries enrolled in a statewide HIV/AIDS-specific
      home- and community-based Medicaid-waiver program. Despite financial eligibility,
      racial minorities, especially African-Americans, were disadvantaged in their
      access to healthcare services during their last months of life; some of these
      racial differences appear to be mediated by the use of the waiver program. There
      was some evidence that access to home care services and case-management
      mechanisms such as those built into the waiver program were an effective means of
      facilitating palliative care by increasing the use of pain medication and
      reducing the likelihood of dying in a hospital.

PMID- 12189714
TI  - Syringe source, use, and discard among injection-drug users in New Haven,
      Connecticut.
AB  - We examined syringe source, use, and discard practices of injection-drug users
      (IDUs) in New Haven, Connecticut, a city with both a legal syringe-exchange
      program (SEP) and non-prescription availability of syringes through pharmacies.
      The population demographics, syringe use, and discard practices of IDUs who
      obtained syringes from various sources were compared using structured interview
      data. Of the 373 IDUs recruited, 268 (72 percent) resided in the city of New
      Haven. Among the New Haven IDUs, 111 (41 percent) reported pharmacies, 36 (13
      percent) reported the New Haven SEP, 90 (34 percent) reported both, and 27 (10
      percent) reported neither as their usual source of syringes in the past six
      months. No significant differences (p value < 0.05) were observed among New Haven
      IDUs who relied on pharmacies versus the SEP. However, IDUs who relied on the SEP
      were significantly less likely to report they threw away used syringes, compared
      with pharmacy users. Both the pharmacies and the New Haven SEP are important
      sources of sterile syringes for IDUs in New Haven. The lower frequency of syringe
      discard by IDUs who obtained their syringes primarily through the SEP indicates
      another public health benefit of programs such as these.

PMID- 12189715
TI  - Risk of cancer among women with AIDS in New York City.
AB  - To evaluate the risk of cancer among women with AIDS in New York City (NYC), we
      compared the cancer experience of AIDS-infected women in NYC with that of the
      general population of women in NYC by matching the population-based New York
      State Cancer Registry with the New York City AIDS Registry. A probabilistic
      algorithm was used to match names, birth dates, and, where available, Social
      Security numbers between 15,146 women with AIDS and 232,902 women with cancer.
      Standardized incidence ratios (SIR) were calculated as the ratio of observed to
      expected cancer cases in the population of NYC women matched for age, race, and
      calendar period of cancer diagnosis. Period-specific relative risks (RR) of
      cancer prevalence prior to AIDS, and incidence at or after AIDS were calculated
      to determine which cancers increased in proximity to an AIDS diagnosis, a
      surrogate marker of increasing immunodeficiency. Analysis was limited to women
      between the ages of 15 to 69 who were diagnosed with AIDS between 1981 and 1994.
      Among 15,146 women diagnosed with AIDS, we found 1,194 matches with the Cancer
      Registry. For cancers included in the 1993 AIDS case definition, the SIR was
      178.49 for Kaposi's sarcoma, 48.97 for non-Hodgkin's lymphoma, and 9.20 for
      invasive cervical cancer. The overall SIR for all non-AIDS-defining cancers was
      2.20. Among non-AIDS-defining cancers, elevated SIRs were found for cancers of
      the lung (7.95), esophagus (7.69), multiple myeloma (7.37), oral cavity and
      pharynx (6.55), Hodgkin's disease (5.65), leukemias (4.52), and rectal/anal
      cancers (3.23). Statistically significant increases in period-specific risks were
      found for all non-AIDS-defining cancers combined, but not for individual cancers.
      Dual screening by two registries and unknown behavioral factors complicate the
      ascertainment of cancer risk. Our results show significantly elevated risks for
      several non-AIDS-defining cancers; these results are consistent with other
      studies of cancers among persons with AIDS. Extension of the time period of
      analysis is required to test for the effects of new anti-viral treatments and
      their association with cancer development among HIV-infected women.

PMID- 12189716
TI  - Tropism-modified adenoviral and adeno-associated viral vectors for gene therapy.
AB  - One of the most rapidly advancing areas of gene therapy is vector development.
      For the majority of gene therapy procedures, efficient and selective transduction
      would provide safe and more effective treatments at optimal vector doses.
      Advances in vector targeting strategies have been rapid within the field of DNA
      based viruses, particularly adenovirus (Ad) and more recently adeno-associated
      virus (AAV) based vectors. Vector targeting at the level of virus: cell
      interaction can be achieved using both non-genetic and genetic methodology. Non
      genetic approaches typically utilise bispecific antibodies that both neutralise
      wild-type virus tropism and provide a new cell binding capacity. For genetic
      targeting strategies, the virus capsid can be engineered to express foreign
      ligands that target selected receptors in the absence or presence of additional
      modification to ablate the virus' natural tropism. This review covers
      technological advances that have led to targeting of Ad and AAV and highlights
      the potential for these 'designer' viruses for future gene-based therapeutics.

PMID- 12189717
TI  - Non-viral approach toward gene therapy of cystic fibrosis lung disease.
AB  - Since Cystic Fibrosis (CF) is an autosomal recessive disorder due to mutations in
      the CFTR (Cystic Fibrosis Transmembrane Conductance Regulator) gene, studies
      towards a gene therapy approach to its treatment followed immediately upon the
      cloning of the gene. It was demonstrated that the insertion of a single copy of
      the wild-type gene restored the normal phenotype in CF cells in vitro.
      Encouraging results were obtained in many in vivo model systems (CF transgenic
      mice) involving viral as well as non-viral vectors, which demonstrated the
      recovery of CFTR function in the airways. These results constituted the basis for
      human studies. Of those with a non-viral approach, a total of seven clinical
      trials using cationic lipids have reported data on efficiency, efficacy and
      safety. An effective gene transfer approach for the treatment of CF lung disease
      is not however imminent: low transfection efficiency and poor maintenance of gene
      expression are so far the main obstacles on this therapeutic path. On the other
      hand, no important adverse effects have been documented and repeated
      administration in humans is possible. The understanding of tissue and cellular
      barriers is a prerequisite for the development of more efficient non-viral gene
      therapy protocols for CF patients. While cationic lipids have been shown to be
      blocked by the mucous airway barrier and not be able to transfect differentiated
      respiratory epithelial cells, a new class of non-viral vectors, cationic
      polymers, are endowed with chemical and biological properties that make them more
      efficient in mediating gene transfer than lipids. Cationic polymers, such as
      polyethylenimine, are promising vectors for CF lung gene therapy.

PMID- 12189718
TI  - Influence of the bystander effect on HSV-tk/GCV gene therapy. A review.
AB  - Despite the development of new therapeutic strategies, cancer remains incurable
      in most patients with advanced disease. A recent potential improvement in
      therapeutic strategies is the concept of suicide gene therapy. After transfection
      with a suicide gene, cells can convert a harmless prodrug into its toxic
      metabolite, resulting in selective elimination of these cells. One of the most
      frequently studied therapeutic strategies is based on transfection with the
      herpes simplex virus thymidine kinase gene (HSV-tk), followed by ganciclovir
      administration. Despite promising results in vitro and in vivo, the antitumor
      effect in clinical trials remains poor, due to very low transfection efficiency.
      However, high percentages of transfected cells are not mandatory for complete
      eradication of a tumor in vivo. Transfected tumor cells appear to be capable of
      inducing the death of neighboring untransfected cells. This cell kill is called
      the "bystander effect". Various attempts have been made to increase this effect.
      A substantial bystander effect could overcome the limitations of low transfection
      efficiency and result in an enhanced and possibly clinically worthwhile antitumor
      effect in patients. This review is focused on the HSV-tk/GCV system and gives an
      overview of current knowledge on the bystander effect in vitro and in vivo. In
      addition, theories concerning its mechanisms and possible approaches to augment
      this effect are discussed. Finally, we give an overview of clinical trials using
      suicide gene therapy.

PMID- 12189719
TI  - Transductional targeting with recombinant adenovirus vectors.
AB  - Replication-deficient adenoviruses are considered as gene delivery vectors for
      the genetic treatment of a variety of diseases. The ability of such vectors to
      mediate efficient expression of therapeutic genes in a broad spectrum of dividing
      and non-dividing cell types constitutes an advantage over alternative gene
      transfer vectors. However, this broad tissue tropism may also turn
      disadvantageous when genes encoding potentially harmful proteins (e.g. cytokines,
      toxic proteins) are expressed in surrounding normal tissues. Therefore, specific
      restrictions of the viral tropism would represent a significant technological
      advance towards safer and more efficient gene delivery vectors, in particular for
      cancer gene therapy applications. In this review, we summarize various strategies
      used to selectively modify the natural tropism of recombinant adenoviruses. The
      advantages, limitations and potential impact on gene therapy operations of such
      modified vectors are discussed.

PMID- 12189720
TI  - Gene therapy strategies to prevent autoimmune disorders.
AB  - Autoimmunity accounts for a significant percentage of human disease and remains a
      challenging syndrome to treat. While systemic immunosuppression can be
      beneficial, the associated toxicity of the pharmacologic agents necessitates an
      antigen-specific approach to silence, eradicate or prevent the genesis of
      autoreactive immune cells. Gene therapy offers the possibility of providing
      precise antigen-targeted therapies, thereby sparing the patient the significant
      toxicity associated with lifelong commitment to chemical immunosuppressives. Gene
      based therapies could include, but are not limited to the manipulation of immune
      networks of tolerance by antigen presenting cell engineering, pro-inflammatory
      cytokine blockade using soluble antagonists expressed from viral vectors as well
      as modulation of immune regulatory networks. The potential utility of gene
      therapy strategies promoting tolerance in two model autoimmune disorders, type I
      diabetes mellitus and rheumatoid arthritis are discussed in this review.

PMID- 12189721
TI  - Polycistronic viral vectors.
AB  - Traditionally, vectors for gene transfer/therapy experiments were mono- or
      bicistronic. In the latter case, vectors express the gene of interest coupled
      with a marker gene. An increasing demand for more complex polycistronic vectors
      has arisen in recent years to obtain complex gene transfer/therapy effects. In
      particular, this demand is stimulated by the hope of a more powerful effect from
      combined gene therapy than from single gene therapy in a process whose parallels
      lie in the multi-drug combined therapies for cancer or AIDS. In the 1980's we had
      only splicing signals and internal promoters to construct such vectors: now a new
      set of biotechnological tools enables us to design new and more reliable
      bicistronic and polycistronic vectors. This article focuses on the description
      and comparison of the strategies for co-expression of two genes in bicistronic
      vectors, from the oldest to the more recently described: internal promoters,
      splicing, reinitiation, IRES, self-processing peptides (e.g. foot-and-mouth
      disease virus 2A), proteolytic cleavable sites (e.g. fusagen) and fusion of
      genes. I propose a classification of these strategies based upon either the use
      of multiple transcripts (with transcriptional mechanisms), or single transcripts
      (using translational/post-translational mechanisms). I also examine the different
      attempts to utilize these strategies in the construction of polycistronic vectors
      and the main problems encountered. Several potential uses of these polycistronic
      vectors, both in basic research and in therapy-focused applications, are
      discussed. The importance of the study of viral gene expression strategies and
      the need to transfer this knowledge to vector design is highlighted.

PMID- 12189722
TI  - Improvement of nonviral gene therapy by Epstein-Barr virus (EBV)-based plasmid
      vectors.
AB  - The nonviral gene transfer technologies include naked DNA administration,
      electrical or particle-mediated transfer of naked DNA, and administration of DNA
      synthetic macromolecule complex vectors. Each method has its advantage, such as
      low immunogenicity, inexpensiveness, ease in handling, etc., but the common
      disadvantage is that the transfection efficiency has been relatively poor as far
      as conventional plasmid vectors are involved. To improve the nonviral gene
      transfer systems, Epstein-Barr virus (EBV)-based plasmid vectors (also referred
      to EBV-based episomal vectors) have been employed. These vectors contain the
      EBNA1 gene and oriP element that enable high transfer efficiency, strong
      transgene expression and long term maintenance of the expression. In the current
      article, I review recent preclinical gene therapy studies with the EBV plasmid
      vectors conducted against various diseases. For gene therapy against
      malignancies, drastic tumor suppression was achieved by gancyclovir
      administrations following an intratumoral injection with an EBV plasmid vector
      encoding the HSV1-TK suicide gene. Equiping the plasmid with carcinoembryonic
      antigen (CEA) promoter sequences enabled targeted killing of CEA-positive tumor
      cells, which was not accomplished by conventional plasmid vectors without the EBV
      genetic elements. Transfection with an apoptosis-inducing gene was also effective
      in inhibiting tumors. Interleukin (IL)-12 and IL-18 gene transfer, either local
      or systemic, induced therapeutic antitumoral immune responses including
      augmentation of the cytotoxic T lymphocyte (CTL) and natural killer (NK)
      activities, while an autologous tumor vaccine engineered to secrete Th1 cytokines
      via the EBV system also induced growth retardation of tumors. Non-EBV
      conventional plasmids were much less effective in eliciting these therapeutic
      outcomes. Intracardiomuscular transfer of the beta-adrenergic receptor gene
      induced a significant elevation in cardiac output in cardiomyopathic animals,
      suggesting the usefulness of the EBV system in treating heart failure. The EBV
      based nonviral delivery also worked as genetic vaccine that triggered
      prophylactic cellular and humoral immunity against acute lethal viral infection.
      All the nonviral delivery vehicles so far tested showed an improved transfection
      rate when combined with the EBV-plasmids. Collectively, the EBV-based plasmid
      vectors may greatly contribute to nonviral gene therapy against a variety of
      disorders, including malignant, congenital, chronic and infectious diseases.

PMID- 12189723
TI  - Preformulation studies as an essential guide to formulation development and
      manufacture of protein pharmaceuticals.

PMID- 12189724
TI  - Aseptic processing of protein pharmaceuticals.

PMID- 12189725
TI  - Fundamentals of thermal sterilization processes.
AB  - Information has been provided in this chapter on the fundamentals of thermal
      sterilization processing. The derivation of various equations presented in the
      text was not discussed; the reader is referred to the references cited for this
      information. Emphasis was placed on the need for good manufacturing practice and
      for control of presterilization bioburden. These considerations will have the
      greatest impact on product quality in the long run. An attempt was also made to
      dispel the notion that sterilization processes always require the most rigorous
      biological challenge for validation. Finally, parametric or process control
      release of terminally sterilized products was discussed. Parametric release is a
      concept that will find greater application in areas other than most heat
      sterilization as the industry continues to derive full benefit from validated
      processes.

PMID- 12189726
TI  - Membrane filtration.

PMID- 12189728
TI  - Quality assurance and quality control for biopharmaceutical products.

PMID- 12189727
TI  - Fundamentals of freeze-drying.
AB  - Given the increasing importance of reducing development time for new
      pharmaceutical products, formulation and process development scientists must
      continually look for ways to "work smarter, not harder." Within the product
      development arena, this means reducing the amount of trial and error empiricism
      in arriving at a formulation and identification of processing conditions which
      will result in a quality final dosage form. Characterization of the freezing
      behavior of the intended formulation is necessary for developing processing
      conditions which will result in the shortest drying time while maintaining all
      critical quality attributes of the freeze-dried product. Analysis of frozen
      systems was discussed in detail, particularly with respect to the glass
      transition as the physical event underlying collapse during freeze-drying,
      eutectic mixture formation, and crystallization events upon warming of frozen
      systems. Experiments to determine how freezing and freeze-drying behavior is
      affected by changes in the composition of the formulation are often useful in
      establishing the "robustness" of a formulation. It is not uncommon for seemingly
      subtle changes in composition of the formulation, such as a change in formulation
      pH, buffer salt, drug concentration, or an additional excipient, to result in
      striking differences in freezing and freeze-drying behavior. With regard to
      selecting a formulation, it is wise to keep the formulation as simple as
      possible. If a buffer is needed, a minimum concentration should be used. The same
      principle applies to added salts: If used at all, the concentration should be
      kept to a minimum. For many proteins a combination of an amorphous excipient,
      such as a disaccharide, and a crystallizing excipient, such as glycine, will
      result in a suitable combination of chemical stability and physical stability of
      the freeze-dried solid. Concepts of heat and mass transfer are valuable in
      rational design of processing conditions. Heat transfer by conduction--the
      dominant mechanism of heat transfer in freeze-drying--is inefficient at the
      pressures used in freeze-drying. Steps should be taken to improve the thermal
      contact between the product and the shelf of the freeze dryer, such as
      eliminating metal trays from the drying process. Quantitation of the heat
      transfer coefficient for the geometry used is a useful way of assessing the
      impact of changes in the system such as elimination of product trays and changes
      in the vial. Because heat transfer by conduction through the vapor increases with
      increasing pressure, the commonly held point of view that "the lower the
      pressure, the better" is not true with respect to process efficiency. The optimum
      pressure for a given product is a function of the temperature at which freeze
      drying is carried out, and lower pressures are needed at low product
      temperatures. The controlling resistance to mass transfer is almost always the
      resistance of the partially dried solids above the submination interface. This
      resistance can be minimized by avoiding fill volumes of more than about half the
      volume of the container. The development scientist should also recognize that
      very high concentrations of solute may not be appropriate for optimum freeze
      drying, particularly if the resistance of the dried product layer increases
      sharply with concentration. Although the last 10 years has seen the publication
      of a significant body of literature of great value in allowing development
      scientists and engineers to "work smarter," there is still much work needed in
      both the science and the technology of freeze-drying. Scientific development is
      needed for improving analytical methodology for characterization of frozen
      systems and freeze-dried solids. A better understanding of the relationship
      between molecular mobility and reactivity is needed to allow accurate prediction
      of product stability at the intended storage temperature based on accelerated
      stability at higher temperatures. This requires that the temperature dependence
      of glass transition-associated mobility, particularly at temperatures below the
      glass transition, be studied in greater depth. The relevance of the concept of
      strong and fragile glasses to frozen systems and freeze-dried solids has only
      begun to be explored. The list of pharmaceutically acceptable protective solutes
      is very short, and more imagination--and work--is needed in order to develop
      pharmaceutically acceptable alternative stabilizers. There is a need for
      technology development in process monitoring, particularly in developing a way to
      measure the status of the product during freezing and freeze-drying without
      placing temperature measurement probes in individual vials of product. The
      current practice of placing thermocouples in vials is uncertain with respect to
      reliability of the data, inconsistent with elimination of personnel in close
      proximity to open vials of product in an aseptic environment, and incompatible
      with technology for automatic material handling in freeze-drying. In addition, a
      method for controlling the degree of supercooling during freezing would allow
      better control of freezing rate and would, in many cases, result in more
      consistent product quality.

PMID- 12189729
TI  - Regulatory considerations in the development of protein pharmaceuticals.

PMID- 12189730
TI  - Formulation development of protein dosage forms.

PMID- 12189731
TI  - [The Spanish Bibliographic Index of the Health Sciences (IBECS) and Actas
      Urologicas Espanolas].

PMID- 12189732
TI  - [Ambulatory major surgery: our experience].
AB  - INTRODUCTION: The first Surgery Ambulatory Unit was created in 1990, at the
      Hospital de Viladecans although in 1982 Polo et al. had commenced a programme of
      strictly ambulatory surgery. The Spanish Services of Urology are going to be
      incorporated to this new style of labour, and, by the moment, with excellent
      results. MATERIAL AND METHODS: We realize a description of the functioning of our
      service inside the Unit of Ambulatory Major Surgery, and a descriptive analysis
      of our activity in above mentioned unit since February 2000(creation date) to May
      2001. RESULTS: 118 patients were operated, being 15% women and 85% men. The most
      frequent surgery done were: hydrocelectomy, orchiopexy, varicocelectomy, vesical
      distensions, Nesbit technique and internal urethrotomy. From the whole of the
      patients, none was increased, and the complication tax was similar to the
      conventional surgery patients. This kind of surgery suppose 17% in 2000 and 19%
      in 2001 of the whole of surgery, with clear increasing tendency in the last
      months. CONCLUSIONS: The Ambulatory Major Surgery is an effective and efficient
      care pattern in which Urology Services are included, so that the degree of
      satisfaction of the patients and the quality offered is similar to the inpatient
      surgery.

PMID- 12189733
TI  - [Results of external radiotherapy in localized cancer of the prostate].
AB  - OBJECTIVE: External radiotherapy is considered to be a modality of treatment with
      a curative purpose for carcinoma de prostata. We have analysed a series of
      patients that received radical irradiation as treatment for tumor prostatic. We
      have the biochemical control results for these patients. We introduce the
      connection of the PSA nadir value (nPSA) and other prognostic variables with the
      survival free of biochemical failure. MATERIAL AND METHODS: Between January 1992
      to January 1998, 46 patients with prostate cancer T1-3 NX M0 received external
      radiotherapy with a curative purpose. A number of 26 of these patients received
      treatment with androgen blockers. The answer to this treatment was established as
      a fall in PSA to levels equal/minor than 1.5 ng/ml. The biochemical relapse was
      established as three rises of PSA over the value of nPSA. RESULTS: We introduce
      the connection between nPSA and prognostic variables (clinic stage, gleason, PSA
      pretreatment y hormonal therapy). Three of these variables--clinic stage, Gleason
      grade and hormonal therapy--were the ones that showed a significantly connection
      with obtaining a low level of PSA. The 3-year actuarial BDFS was of 69.5%. The
      BDFS was of 84.3%, 9% and 6% for a value of nPSA of < or = 1 ng/ml, 1-2 ng/ml and
      > 2 ng/ml respectively (p < 0.05). CONCLUSION: Radiotherapy seems to be a good
      therapeutical option with patients suffering from localised prostate carcinoma.
      The nPSA value after radiation is a good early determinant of outcome.

PMID- 12189734
TI  - [Prostatic exfoliative cytology obtained from urine samples after massage.
      Initial results].
AB  - INTRODUCTION: The same as the exfoliative cytology is a routine method to
      diagnose bladder tumour, the prostatic cytology obtained after massage may become
      a useful procedure to diagnose prostate cancer. OBJECTIVE: To obtain suitable
      prostatic cytologic material. To establish the role of the exfoliative cytology
      to diagnose cancer. MATERIAL AND METHODS: We made a prospective longitudinal
      descriptive study with 60 patients out of 150 (all of them with possible prostate
      cancer) for two years. We compared cytologic discoveries (urine after massage)
      with histological parameters (biopsies). RESULTS: When the cytology fulfills a
      series of requirements (a high number of prostatic cells, anisokariosis and
      antibodies Ki-67+) and these are compared with the histological data, we obtained
      a specificity of 100% and a sensibility of 67% for prostatic cancer. With this
      information the cytology reaches a predictive value of 100% and negative of 92%.
      CONCLUSIONS: It is possible to obtain prostatic cytologic material in a simple
      and easy way. The prostatic cytology may become a valid and useful method to
      diagnose the carcinoma of the prostate. Also this material can be used for
      multiple diagnostic, follow-up and research procedures.

PMID- 12189736
TI  - [Cutaneous metastasis of a transitional-cell bladder carcinoma].
AB  - Transitional cell of bladder carcinoma metastasizing to the skin is uncommon
      finding, generally appearing in the final stages such that occurred in our
      patient that indicated a poor prognosis. A lesion located in the pubic region and
      internal face of the left lower limb with at erythematous, indurated, and
      aggregated appearance was found. The histological examination of the specimen
      after cold biopsy demonstrated cutaneous metastasis from transitional cell
      carcinoma.

PMID- 12189737
TI  - [Nephrogenic bladder adenoma associated with glandular cystitis.
      Immunohistochemical study and significance].
AB  - A histopathological and immunohistochemical study of a case of nephrogenic
      adenoma of the bladder associated to glandular cystitis is presented with a very
      similar immunostaining to adenomatoid tumors in other organs and probably of a
      mesothelial origin. Its pathogenesis seems to correspond to a metaplastic change
      of the bladder's urothelium through anomalous differentiation of the reserve
      cells faced with different irritating agents. Because of its benign
      characteristics, we think that treatment can be confined to endoscopic
      observation and conservative technique.

PMID- 12189735
TI  - [Expression of p21ras in locally confined renal adenocarcinoma and its prognostic
      implications].
AB  - OBJECTIVE: The p21ras protein is encoded by the three ras genes (H-, K- and N
      ras) and participate in the regulation of normal cell growth and cell
      differentiation. The objective of this study is to determine the expression of
      this protein in locally confined renal cell carcinoma, as well as its relations
      with different histopathological variables and their prognostic implications.
      METHOD: 58 renal cell carcinomas, in pT1-T3a N0 M0 (TNM 1997) stages, treated by
      radical or partial nephrectomy with curative intention. We analysed different
      clinical and anatomopathological variables, as well as expression of p21ras in
      paraffinated tissue, using immunohistochemical techniques. RESULTS: The mean
      percentage of stained nuclei was 6.1%, with a range lying between 0 and 45%. We
      did not obtain statistically significant association between expression of p21ras
      and the tumour size (p = 0.698), the nuclear grade (p = 0.676) or the
      histopathological stage (p = 0.095). The survival analysis also did not show
      significant differences when we stratified the patients using the mean value of
      the sample as reference point (p = 0.134). CONCLUSIONS: Expression of p21ras was
      not demonstrated to be related to any of the histopathological variables
      analysed: size, grade and stage, or with survival. Therefore, this protein does
      not appear to be related to the evolution of renal cell carcinoma.

PMID- 12189738
TI  - [Massive bilateral adrenal hemorrhage after conservative tumor surgery in the
      isthmus of a horseshoe kidney].
AB  - OBJECTIVE: To present a fatal case of massive bilateral suprarrenal haemorrhage
      (MBSH) after partial nephrectomy. CLINICAL CASE: An 82 year old male treated with
      oral anticoagulants was diagnosed by means of CT scan and arteriography of having
      an avascular tumor located at the isthmus of a horseshoe kidney. A tumorectomy
      with safety surgical margins was performed; It was diagnosed of having a renal
      adenocarcinoma, which was almost completely necrotic. During the postoperative
      period, the patient presented abdominal pain, nausea, fever, hypotension and
      severe respiratory distress. Biochemical studies showed mild hyponatremia and
      azotemia, accompanied by anemia, leucocytosis and thrombocytosis. An abdominal CT
      scan demonstrated a MBSH, which produced the patients death soon afterwards.
      DISCUSSION: Tumoral pathology of horseshoe kidneys presents important topographic
      and anatomopathologic differences with respect to non-fused kidneys. MBSH is a
      rare complication of many stress processes especially if an anticoagulant
      treatment coexists. The treatment has to be initiated as soon as we suspect MBSH,
      which should be confirmed by hormonal determinations and/or the presence of
      hyperdense suprarenal lesions at the CT scan.

PMID- 12189739
TI  - [Bilateral hydronephrosis secondary to ileocolic Crohn's disease].
AB  - Unilateral hydronephrosis can complicate a far from negligible number of patients
      with Crohn's disease. Bilateral hydronephrosis associated with Crohn's disease is
      a much more unusual entity. In the other hand, the treatment for this condition
      is still controversial. We present the case of a 44 year old female with several
      bowel obstruction episodes caused by ileocolic Crohn's disease. During the last
      episode she was also diagnosed of bilateral hydroureter and hydronephrosis. After
      the resolution of the bowel obstruction and the placement of a double J catheter
      in both ureters, the patient was operated. Ileocolic resection and bilateral
      ureterolysis with omental wrapping were performed. Although urinary and wound
      infection complicated the postoperative course, and a enterocutaneous fistula had
      to be medically treated one year later, the patient is now free of symptoms and
      her renal function is normal.

PMID- 12189740
TI  - [Secondary prostatic lymphoma in a kidney transplant patient].
AB  - Lymphoma involving the prostate is rare, both as a primary and as a secondary
      presenting. Usually the prognosis remains poor. The clinical presentation is
      similar to that of other lower urinary tract obstructions, in fact prostatic
      lymphoma must be considered in patients with these symptoms, particularly in
      patients with prior history of systemic lymphoma. We report a case of a kidney
      transplantation in a male patient, diagnosis of lymphoma non Hodgkin, with later
      recurrence in prostate.

PMID- 12189741
TI  - [Nephrectomy of a giant hypernephroma (5,150 g)].
AB  - We report a giant renal adenocarcinoma (5150 g weight) excised in a 52 years old
      male. He presented a severe clinical symptoms: serious haematuria, fever (40
      degrees C), left flank pain, abdominal discomfort and weight loss (10 kg). The
      patient underwent left renal artery embolization because of severe anemia (blood
      transfusion: 4 uu) but haematuria didn't decrease; that's why radical surgery was
      advised. Until our knowledge this case is the largest removed kidney
      adenocarcinoma published in the world literature (Medline 1966-2001).

PMID- 12189742
TI  - [Bladder metastasis of a stomach carcinoma. Presentation of a case].
AB  - Metastatic tumors account for a small percentage within bladder neoplastic
      pathology. The presence of signs of bladder neoplasm in a patient with
      malignancies in other location must aware us about its metastatic origin. One of
      the most frequent locations of the primary tumor is the stomach. Its evolution is
      always bad. We present a case of a woman who previously had undergone surgery for
      a gastric carcinoma, and later suffered a metastatic bladder affectation. We make
      special attention in the clinic presentation, very similar to the typical
      transitional cell carcinoma, its anatomopathological diagnosis after
      transurethral resection (T.U.R.), and its evolution. We make a brief revision of
      the bladder metastatic pathology.

PMID- 12189743
TI  - [Penile prostheses and infection].
AB  - Infection of penile prostheses, estimated to occur in 3% of cases, represent the
      major complication of this type of prosthesis. Early sepsis occurs during the
      first week and presents in the form of frank clinical features (pain, erythema,
      penile discharge); highly virulent bacteria are isolated, such as Staphylococcus
      aureus. Late sepsis occurs after an interval of several weeks to several months
      with less specific clinical features; Staphylococcus epidermidis is isolated in
      more than 50% of cases. Conventional treatment of these infections consists of
      antibiotics adapted to the local flora and removal of the prosthesis, sometimes
      followed by deferred reimplantation. Prosthetic material salvage procedures are
      now proposed. Patient-related risk factors for infection include diabetes,
      urinary tract infection and immunodepression, while procedure-related risk
      factors include the length of hospital stay, poor operative technique, prolonged
      operating time and iatrogenic urethral injuries. Prevention of sepsis of penile
      prostheses is based on prevention of these risk factors and prophylactic
      antibiotics or prolonged antibiotic therapy.

PMID- 12189744
TI  - [Comparison of a phytotherapeutic agent (Permixon) with an alpha-blocker
      (Tamsulosin) in the treatment of benign prostatic hyperplasia: a 1-year
      randomized international study].
AB  - OBJECTIVE: While the lipidosterolic extract (LSESr) of Serenoa repens--Permixon-
      has been shown to have an equivalent efficacy to finasteride in patients with
      benign prostatic hyperplasia (BPH), to date, there has been no valid comparison
      of phytotherapy with alpha-blockers. The aim of this study was to assess the
      equivalent efficacy of Permixon and tamsulosin. METHODS: Eight hundred and eleven
      men with symptomatic BPH (international prostdate symptom score, I-PSS > or = 10)
      were recruited in 11 European countries for a 12-month, double-blind randomized
      trial. After a 4-week run-in period, 704 patients were randomly assigned to
      either tamsulosin 0.4 mg per day (N = 354) or Permixon 320 mg per day (N = 350).
      I-PSS, QoL and maximum urinary flow rate (Qmax) were evaluated at baseline and
      periodically for 1 year. Prostate volume and serum prostate-specific antigen
      (PSA) were measured at selection and at endpoint. The endpoint analysis was
      performed on the per-protocol (PP) population of 542 patients (tamsulosin: N =
      273; Permixon: N = 269). RESULTS: At 12 months, I-PSS decreased by 4.4 in each
      group and no differences were observed in either irritative or obstructive
      symptom improvements. The increase in Qmax was similar in both treatment groups
      (1.8 ml/s Permixon, 1.9 ml/s tamsulosin). PSA remained stable while prostate
      volume decreased slightly in the Permixon-treated patients. The two compounds
      were well tolerated, however, ejaculation disorders occurred more frequently in
      the tamsulosin group. CONCLUSION: This study demonstrated that Permiwon and
      tamsulosin are equivalent in the medical treatment of lower urinary tract
      symptoms in men with BPH, during and up to 12 months of therapy.

PMID- 12189745
TI  - [Tamsulosin with or without Serenoa repens in benign prostatic hyperplasia: the
      OCOS trial].
AB  - OBJECTIVE: In the treatment of the symptoms of benign prostatic hyperplasia
      (BPH), a French guideline opposes the use of drugs in conjunction, in the absence
      of proven utility. The OCOS trial therefore compared one of the possible drug
      combinations (tamsulosin and Serenoa repens) with tamsulosin alone, to see if
      there was any difference in effectiveness and to evaluate the clinical tolerance
      of each in patients with symptoms of BPH. MATERIAL AND METHODS: In this double
      blind, randomised trial, patients had to have an IPSS (International Prostate
      Symptom Score) > or = 13 and a Qmax between 7 and 15 mL/s. Tamsulosin (0.4 mg)
      was to be administered once a day for 52 weeks, with, twice daily, a placebo
      (TAM) or Serenoa repens 160 mg (TAM + SR). RESULTS: 352 patients were recruited
      by 47 centres; 329 (average age 65) were randomised: 161 into the TAM group and
      168 into the TAM + SR group. No statistically significant difference was found
      between the two groups, neither for the major end-point [change in total IPSS
      between the baseline value and the final evaluation (TAM: -5.2; TAM + SR: -6.0; p
      = 0.286)], nor for the secondary end-points [changes in the voiding scores (p =
      0.239) and in filling scores (p = 0.475) of the IPSS, Qmax (p = 0.564),
      percentage of respondents according to the IPSS (p = 0.361), improvement in
      quality of life (IPSS-QoL: p = 0.091; UROLIFE BPH QoL: p = 0.442), safety].
      CONCLUSION: The addition of Serenoa repens to tamsulosin did not provide any
      significant benefit to the patients: the OCOS trial does not cast doubt on the
      guideline applicable to the treatment of BPH.

PMID- 12189746
TI  - [What are the arguments in favour of local allocation of kidneys harvested for
      transplantation?].
AB  - The rules of organ allocation allow one of the two kidneys harvested to be
      transplanted locally while the other is exchanged. This rule of local priority
      does not exist in all countries. The purpose of this article is to determine
      whether this rule provides a benefit for the patient. 804 locally harvested
      kidneys were compared to 1196 exchanged kidneys transplanted between 1970 and
      2000 by the same renal transplantation team. RESULTS: The cold ischaemia time was
      shorter (-6 h), the number of cases of HLA identity was lower (-0.8), the rate of
      acute tubular necrosis was lower (-9), and the median graft survival of was 7
      months longer for local kidneys. DISCUSSION: An article analysing the North
      American register reached similar conclusions: the local attribution rule reduces
      the cold ischaemia and the graft loss at one year. CONCLUSION: The local
      attribution rule has the advantage of increasing the organ harvesting rate from
      borderline donors, reducing the cold ischaemia, and improving the results: this
      rule should therefore be maintained.

PMID- 12189747
TI  - [Hydatid cyst of the kidney based on a series of 34 cases].
AB  - AIM: Hydatid disease is endemic in some countries, where it constitutes a real
      public health problem. It can affect any, but the kidney is a relatively rare
      site, representing 2% to 4% of all visceral sites. Renal hydatid cyst only
      presents at the stage of complications. Laboratory tests may suggest the
      diagnosis, which is confirmed by radiology. Renal hydatid cyst raises therapeutic
      problems making conservative surgery difficult. The objective of this paper is
      the find the best adapted treatment. MATERIAL AND METHOD: 34 consecutive cases of
      renal hydatid cyst (1980-2001) were observed in 23 men and 11 women with a mean
      age of 42 years (range: 15-73 years). The clinical features were dominated by
      pain (63%), a mass (26%), hydaturia (11.4%), haematuria (31.4%), prolonged fever
      (23%) and hypertension (3%). Intravenous urography performed in all patients
      showed calcifications in 5 cases, a mass syndrome in 11 cases and silent kidney
      in 2 cases. Abdominal CT, performed in 8 patients, was necessary whenever the
      diagnosis remained uncertain, particularly in the case of pseudoneoplastic cysts.
      However, ultrasonography, performed in 30 patients, remains the preferred
      diagnostic examination. RESULTS: Treatment consisted of resection of the
      prominent dome in 23 cases, pericystectomy in 5 cases, 1 partial nephrectomy and
      6 total nephrectomies. An associated procedure was performed during the same
      operation (hepatic, peritoneal hydatid cyst) in 3 cases, and was deferred
      (pulmonary hydatid cyst) in 1 case. The postoperative course was marked by
      urinary fistula in 2 cases and suppuration of the residual cavity in 1 case,
      treated by ultrasound-guided aspiration-drainage. CONCLUSION: The resection of
      the prominent dome is the most adapted treatment whenever possible.

PMID- 12189748
TI  - [Value of laser ureteroscopy with semi-rigid ureteroscope in the treatment of
      stones less than 2 cm situated above the iliac vessels : Report of a
      retrospective series of 460 consecutive cases].
AB  - OBJECTIVE: To evaluate the value of retrograde ureteroscopy in the treatment of
      stones less than 2 cm situated above the iliac artery. MATERIAL AND METHOD:
      Between September 1989 and December 1998, 460 consecutive patients, aged 14 to 86
      years, presenting with stones situated above the iliac vessels and measuring less
      than 2 cm were initially managed by fine (7.5 F) semi-rigid ureteroscopy with
      CANDELA laser fragmentation in the majority of cases. All operations were
      performed under general anaesthesia with continuous muscle relaxation. The
      operation was performed by the same operator in every case. In 50 cases (10.65%),
      a complementary extracorporeal lithotripsy session was performed following the
      operation and in 13 cases (2.82%) a second ureteroscopy was necessary. RESULTS:
      352 patients (76.5%) were free of any residual fragments after a single laser
      ureteroscopy session. 415 patients (90.21%) were free of any stone fragments at
      the 3rd postoperative month. Complications consisted of 28 cases of ureteric
      perforations, which were all cured by double J stenting, and 7 cases of minor
      haematuria during the operation. No long-term complication was observed.
      CONCLUSION: Ureteroscopy with laser lithotripsy using a fine, semi-rigid
      instrument, is a reliable technique to treat stones situated above the iliac
      vessels, provided appropriate anaesthesia and continuous muscle relaxation are
      ensured. This procedure is associated with a low morbidity and therefore
      constitutes an effective alternative in the case of failure of ESWL for the
      treatment of stones less than 2 cm situated above the iliac vessels.

PMID- 12189749
TI  - [Biochemical monitoring of prostate cancer treated exclusively by radiotherapy:
      prognostic value of pretreatment PSA, PSA nadir and PSA half-life].
AB  - OBJECTIVES: Retrospective evaluation of the prognostic value of pretreatment PSA,
      PSA nadir and PSA half-life compared to grade and stage after treatment of
      prostate cancer by radiotherapy. PATIENTS AND METHODS: 122 patients (19 T1
      (15.6%), 31 T2a (25.4%), 26 T2b (21.3%), 20 T3a (16.4%), 19 T3b (15.6%), 7 Tx
      (5.7%)) treated by exclusive radiotherapy were studied with a median follow-up of
      75.4 months. Treatment consisted of high energy irradiation to the prostate for
      31 patients (25.4%) and to the pelvis and prostate for 91 patients (74.6%). PSA
      was assayed retrospectively. The influence of various parameters on the absence
      of laboratory failure, defined according to the ASTRO criteria, and on overall
      survival was studied by univariate and multivariate analysis with a Cox model.
      RESULTS: 29.5% of patients did not develop any biochemical recurrence after a
      mean follow-up of 82 months, while biochemical recurrence occurred in 70.5% of
      patients after a mean interval of 5 months. Among these patients, 28 (33%)
      developed clinical recurrence after a mean interval of 26 months (4 to 80 months)
      leading to death in 17 cases. The modalities of irradiation and pretreatment PSA
      had no influence on the prognosis. The median PSA nadir of patients without
      recurrence was 0.24 ng/ml. The recurrence rate was lower for a PSA nadir less
      than 0.5 ng/ml for biochemical recurrence (45.5% vs 86.8%) (p < 0.0001) and
      clinical recurrence (9.1% vs 31.6%) (p < 0.05). On multivariate analysis, the PSA
      nadir (p = 0.009), PSA half-life (p < 0.001) and Gleason score (p = 0.004) were
      prognostic factors influencing survival, while PSA nadir was the only prognostic
      factor for biochemical recurrence (p = 0.001). Classification of patients into
      two groups with a significantly different prognosis according to the presence or
      absence of at least two favourable prognostic factors (PSA nadir less than 0.5
      ng/ml, Gleason score less than 7, PSA half-life greater than 6 months) showed
      that the 9-year mortality rate was twofold higher in the poor prognosis group
      than in the good prognosis group (85.5% versus 38.6%). CONCLUSION: A nadir PSA
      level less than 0.5 ng/ml, a PSA half-life greater than 6 months and a Gleason
      score less than 7 were predictive of a low risk of biochemical recurrence and
      prolonged survival after treatment by exclusive radiotherapy, in our patients.

PMID- 12189750
TI  - [Male infertility due to azoospermia and in vitro fertilization assisted by ICSI.
      Findings based on a prospective study of our first 42 patients].
AB  - INTRODUCTION: Our experience of ICSI began in 1997. This study reviews our four
      year experience based on 42 consecutive couples. MATERIAL AND METHOD: Between
      February 1997 and December 2000, 42 sterile couples due to male infertility were
      treated by ICSI. Surgical exploration and "open" gamete collection were proposed
      regardless of the predefined type of azoospermia, obstructive or non-obstructive.
      RESULT: Seventy one cycles were performed: ICSI used epididymal spermatozoa in 49
      cycles, and testicular spermatozoa in 22 cycles. The fertilization rate was 76%
      for fresh semen and 87% for frozen semen. The fertilization rate was 88% for
      epididymal spermatozoa and 68% for testicular spermatozoa. 13 pregnancies were
      obtained (18.3%), 11 babies were born at term including 3 twin pregnancies. No
      significant difference was observed between fresh and frozen semen, or between
      obstructive and non-obstructive azoospermia. CONCLUSION: IVF-ICSI applied to
      sterility due to male infertility has revolutionized the management of sterile
      couples. However, as for any new procedure in medicine, we must be vigilant, as a
      sufficient follow-up is necessary to definitively evaluate the safety of ICSI,
      especially in terms of the risk of genetic abnormalities.

PMID- 12189751
TI  - [Epidemiology of urological emergencies in a teaching hospital].
AB  - OBJECTIVES: To quantitatively evaluate the emergency activity of a teaching
      hospital urology department. To determine the epidemiology of urological medical
      and surgical emergencies. MATERIAL AND METHOD: Single-centre prospective study
      conducted in one of the 9 teaching hospital urology departments of the Paris
      region equipped with an emergency room. The on-call team consisted of an intern
      and a hospital student on the spot, a Senior Registrar on call. Evaluation was
      based on daily computer records of all consultations performed by the intern
      outside of the urology department, and all emergency surgical operations
      performed during the out-of-hours period (8:00 p.m. to 8:00 a.m.). RESULTS: A
      total of 1,715 consultations were performed, 15.6% of which required admission to
      hospital. Eleven per cent of consultations in the emergency department were
      transferred from another centre. Emergency surgery was performed in 5% of cases.
      37 multi-organ harvests and 54 renal transplantations were also performed during
      this same period. Mean age: 53.18 years (range: 15-100). 12% of patients were
      over the age of 80 years. Sex-ratio: 78% of males, 22% of females. The most
      frequent presenting complaint was low back pain (25%). The diseases most
      frequently encountered were infectious (19.2%). 30% of emergency surgical
      operations were performed for drainage of obstructive pyelonephritis. Bladder
      tumours were the cancers most frequently responsible for emergency consultations
      (35%) and traumatology represented 8.7% of emergency consultations. CONCLUSION:
      Urological emergencies in a teaching hospital constitute a distinct clinical
      activity, which requires specific material and human resources. This exhaustive
      study could be used as a basis for review of the organization of the management
      of urological emergencies.

PMID- 12189752
TI  - [Is one-stage ureterocele repair possible in children?].
AB  - AIM: To determine the long-term results of ureterocele repair, bearing in mind
      the relative rarity of the malformation, its very polymorphic appearance and the
      diversity of treatments. MATERIAL AND METHODS: Long-term results were assessed by
      postoperative follow-up of 126 children with 131 ureteroceles between 1970-2000.
      RESULTS: With a mean follow-up of 72 months, only 64.2% of children were cured
      after a one-stage procedure. According to the anatomical type, favourable results
      were obtained in 81.6% of cases with a single lumen and 57.9% of cases with a
      double lumen. Treatment success rates for single or double lumens were 73% in the
      case of intravesical implantation and only 53.9% (34/63 children) in ectopic
      forms. According to the technique, cure rates were 67.6% after distal incision in
      34 children, 61.9% after total nephrectomy or superior pole nephrectomy in 42
      children, 50% after ureterocele repair and ureterovesical reimplantation in 20
      patients, 75% after total resection of the pathological lumen, parietal
      reconstruction and ipsilateral and/or contralateral reimplantation in another 20
      patients. CONCLUSIONS: A one-stage procedure is only able to cure 2/3 of
      patients. In view of the tendency to progressive regression of often monstrous
      distensions during the neonatal period, first-line treatment should consist of a
      distal incision, followed, in the case of recurrent infections, by partial or
      total nephrectomy, while reserving the intravesical approach to cases with
      recurrent pyelonephritis. When this surgery is performed on older children or
      adolescents, the ureteroceles will be smaller with a lesser risk of sphincter
      damage.

PMID- 12189753
TI  - [Benign retroperitoneal schwannoma: report of three cases].
AB  - Schwannoma is a tumour arising from Schwann cells. It has a variable presentation
      and its preoperative diagnosis is difficult. Retroperitoneal schwannoma is an
      exceptional site. Although the great majority of schwannomas are benign,
      malignant forms also exist, frequently associated with Von Recklinghausen
      syndrome (4% of cases) or other neurofibromatoses. The authors report three cases
      of benign retroperitoneal schwannoma discovered in a context of low back pain,
      altered bowel habit or incidentally, The frequency, diagnosis, imaging and
      treatment of this rare tumour are discussed.

PMID- 12189755
TI  - [Bilateral non-secreting adrenal cortical adenoma ].
AB  - Non-secreting malignant adrenal cortical adenoma is rare and the bilateral form
      is exceptional. Diagnosis is often delayed and it has a very poor prognosis. The
      authors report a case of bilateral adrenal cortical adenoma in a 53-year-old man.

PMID- 12189754
TI  - [Ruptured aneurysm of the renal artery: a rare cause of macroscopic hematuria ].
AB  - The authors report a case of ruptured aneurysm of the renal artery in a 70-year
      old man urgently admitted for massive haematuria and shock. As a result of a
      rapid diagnosis, ex situ resection of the aneurysm was performed with
      reconstruction of the renal artery pedicle using a vein graft and autologous
      renal transplantation in the iliac fossa. The patient had a favourable course at
      one year with normal renal function on laboratory tests and isotope scan. The
      authors review the literature concerning the epidemiology, classification,
      clinical features and management of aneurysms of the renal artery.

PMID- 12189756
TI  - [Adrenal tuberculous pseudotumour].
AB  - Tuberculous pseudotumour of the adrenal gland with no other extra-adrenal sites
      of tuberculosis is a very rare entity. The authors describe the case of a 24-year
      old patient in whom ultrasound and CT revealed a right adrenal mass.
      Adrenalectomy was performed by laparoscopy and the aetiological diagnosis was
      only established after histological examination of the operative specimen.

PMID- 12189757
TI  - [Solitary giant retroperitoneal neurofibroma].
AB  - Retroperitoneal nerve sheath tumors (RNST), which include benign and malignant
      schwannomas and neurofibromas, are rare. A 71-year-old woman was complaining of
      flank pain. Ultrasonography and computed tomography revealed a retroperitoneal
      tumor measuring 22 x 15. It was successfully removed and extirpated through a
      midline laparotomy incision. It weighed 7 kgs. Histochemical and
      immunohistochemical staining of the tumor are useful for the diagnosis of
      solitary neurofibroma. After a two year follow-up, the patient is in good health,
      asymptomatic and without evidence of local recurrence.

PMID- 12189759
TI  - [Spontaneous perirenal haematoma caused by a renal adenoma].
AB  - Spontaneous perirenal haematoma is a rare entity and is due to an underlying
      renal disease. Renal tumours represent the majority of causes of atraumatic renal
      rupture. The authors report a case in which perirenal haematoma, due to
      spontaneous rupture of a renal adenoma, 2 cm in diameter, was treated by radical
      nephrectomy.

PMID- 12189758
TI  - [Clear cell sarcoma of the kidney: 3 case reports].
AB  - Clear cell carcoma of the kidney is a distinct, highly malignant pediatric
      neoplasm. Its occurrence in adults is extremely rare and the subject of isolated
      case reports. MATERIAL AND METHODS: We report 3 cases of clear cell sarcoma of
      the kidney in one men and two women between 23 and 65 years old (mean age is 40
      years). A radical nephrectomy with hilar lympgh node dissection was accomplished.
      A combination chemotherapy regiment (cisplatin and doxorubicin) was performed on
      6 cycles in 1 case. The other 2 case was not underwent chemotherapy or radiation.
      RESULTS: In the patient underwent the combination chemotherapy there was not
      evidence of tumor in the abdomen and thorax on CT Scan 4 years later. In one of
      the two patient not underwent chemotherapy or radiation, the CT scan revealed a
      left psoas reccurrence three month later; therapy consisted for surgery without
      chemotherapy or radiation. Four month later, tfe CT scan revealed a reccurrence
      in the left retroperitoneal region and liver and speen metastasis. The patient
      was dead two month later. The other patient not underwent chemotherapy or
      radiation was dead seven month after nephrectomy. CONCLUSION: Optimal treatment
      is unknown, and surgery; radiotherapy and chemotherapy are used alone but mostly
      in combination.

PMID- 12189761
TI  - [Focal bacterial nephritis: diagnosis and treatment].
AB  - Focal bacterial nephritis or lobar nephronia represents an acute localized non
      liquefactive infection of the kidney caused by bacterial infection. This is an
      uncommon form of pyelonephritis that can affect both adults and children. Imaging
      techniques, particularly CT scan, are necessary for diagnosis and to distinguish
      it from other conditions (abscess or renal masses) that require a different
      treatment. The authors describe a case of acute lobar nephronia in a 24-year-old
      man.

PMID- 12189760
TI  - [Intrathoracic kidney due to diaphragmatic hernia: a case report].
AB  - The authors report a case of incidental discovery of a right intrathoracic kidney
      in a 70-year-old man, in July 1994, on intravenous urography performed for
      assessment of benign prostatic hyperplasia. This intrathoracic ectopic kidney is
      due to a diaphragmatic hernia and may be either congenital or acquired. It must
      be distinguished from true ectopic kidney, present during foetal life [4], which
      requires a high origin of the renal artery from the aorta with elongation of the
      ureter. Intrathoracic kidney due to diaphragmatic hernia is usually asymptomatic,
      but may be responsible for severe clinical symptoms with respiratory distress
      occurring in a newborn infant with this malformation. The diagnosis of
      intrathoracic kidney must be considered in the presence of a mediastinal mass on
      chest x-ray and is confirmed by intravenous urography, or even thoracic computed
      tomography. Apart from its rare complications, this anomaly does not require any
      specific treatment.

PMID- 12189762
TI  - [Unusual clinical presentations of tumours of the renal pelvis. Report of two
      cases ].
AB  - Chronic irritation induced by stones and urinary stasis can be responsible for
      squamous and sometimes glandular metaplasia of the urothelial epithelium with
      secondary carcinomatous transformation. The authors report two cases of tumour of
      the renal pelvis associated with stone pyonephrosis in one case and ureteropelvic
      junction syndrome in the other.

PMID- 12189763
TI  - [Transcaval ureter].
AB  - The authors report a case of transcaval ureter complicated by acute obstructive
      pyelonephritis in a 54-year-old patient. Transcaval ureter is a rare congenital
      malformation of the infra-renal inferior vena cava (IRIVC) in which the right
      ureter passes through a venous ring composed of localized duplication of the vena
      cava due to persistence of the right posterior cardinal and supracardinal veins.

PMID- 12189764
TI  - [Vesicosphincteric disorders and neurosyphilis].
AB  - Voiding disorders secondary to neurosyphilis have now become rare. The authors
      report a case of a patient with arthritis of the knee associated with dysuria and
      chronic urinary retention. Urethrocystography showed a large bladder with post
      voiding residual urine. Urodynamic assessment revealed detrusor areflexia. The
      aetiological diagnosis was neurosyphilis. Serological tests for sexually
      transmitted diseases must be systematically performed in patients presenting with
      idiopathic voiding disorders.

PMID- 12189765
TI  - [Leiomyoma of the urinary bladder].
AB  - Benign mesenchymal tumors of the bladder are rare. Leiomyoma is the most common
      mesenchymal tumor of the bladder. We report a new case. A 50-year-old woman
      presented with total hematuria. Complementary investigations (ultrasonographic,
      intravenous urography) showed an intravesical solid mass, arising from the
      bladder dome. Cystoscopic examination suggested a benign tumor, which was
      confirmed by pathologic assessment of biopsy. Partial cystectomy was performed.
      Postoperative course was uneventful. Pathologic examination showed a leiomyoma.
      Leiomyoma of the urinary bladder is a rare benign tumor. Its prognosis is good,
      the treatment being exclusively surgical.

PMID- 12189766
TI  - [The vesico-acetabular fistula].
AB  - We report the first case of a vesico-acetabular fistula observed with a septic
      arthritis of the left hip late treated in a 22-year-old man. The treatment of
      this fistula is surgical.

PMID- 12189767
TI  - [Testicular microlithiasis and cancer of the testis].
AB  - The authors report the case of a patient with a history of testicular
      cryptorchidism followed for 4 years for infertility and who developed seminoma.
      Bilateral testicular microlithiasis was initially detected on ultrasonography. On
      the basis of this case and a review of the literature, the authors discuss the
      aetiopathogenesis and management of these microscopic stones in a context of
      cancer.

PMID- 12189768
TI  - [Urological consequences of pudendal nerve trauma during orthopedic surgery:
      review and practical advice].
AB  - Pudendal nerve trauma is a rare complication of orthopaedic and traumatological
      surgery, which occurs after traction of the pelvis on an orthopaedic table fitted
      with a pelvic support. This trauma is generally due to crushing of the nerve
      against the central part of the table or stretching of the pudendal nerve due to
      excessive traction during fractures of the femur. the urological consequences of
      this neurological trauma present in the form of disorders of perineal
      sensitivity, which usually rapidly resolve spontaneously, or vesicosphincteric
      and/or erectile disorders, which have a more pejorative course and which can
      sometimes persist. The prognosis depends on the severity of the symptoms and the
      results of electrophysiological studies, which are reserved for serious lesions.
      This investigation identifies the level of the neurological lesion. Surgical
      decompression, rarely indicated, can be necessary in the case of serious and
      persistent sensory or motor lesions. Patients must be clearly informed about this
      possible neurological complication before an operation on the orthopaedic table
      as part of good surgical practice.

PMID- 12189769
TI  - [Tumours induced by radiotherapy and chemotherapy].

PMID- 12189770
TI  - [Treatment of genito-urinary prolapses by spinuos fixation with a polypropylene
      prosthesis].
AB  - This article describes an original technique for transvaginal repair of prolapses
      concerning the anterior and middle stages of the pelvis. This operative technique
      uses a polypropylene prosthesis binding the pelvic structures of the anterior and
      middle stages to the small sacro-sciatic ligaments. The very satisfactory results
      achieved let us think that this technique will take a great place in the
      treatment of the genito-urinary prolapses.

PMID- 12189771
TI  - [Urethroplasty and separation of the corpora cavernosa for hypospadias repair].
AB  - Hypospadias is a frequent malformation and its treatment is not devoid of
      complications, particularly fistulas. The authors describe the department's
      surgical technique (modified Duplay technique). Urethroplasty is no longer
      performed by simple approximation of the urethral plate without dissection. The
      inferior surface of corpora cavernosa is exposed as far as the lateral border and
      as far as the summit in the glans, allowing tension-free suture of urethral
      tissues with a lengthening effect of this intermediate plane. This completes
      correction of chordee and especially "bucket-handle" glans and protects the
      reconstructed urethra and proximal urethra. The risk of fistula is therefore
      reduced (2 cases out of 51). This technical modification can be used to treat all
      forms of distal hypospadias (glanular, glanulo-preputial, and anterior penile).
      It has also been used for several cases of more severe hypospadias. These good
      results must be confirmed in a larger series of patients.

PMID- 12189772
TI  - [Francois Gigot de La Peyronie(1678-1747), benefactor of surgery and supporter of
      the fusion of medicine and surgery, and the disease that bears his name].
AB  - Francois Gigot de La Peyronie, first surgeon to Louis XV, definitively
      distinguished surgeons from the company of barbers and, by giving them a charter,
      placed them on an equal footing with physicians. The creation of Academie Royale
      de Chirurgie, in 1731, that LAPEYRONIE, presided for 11 years, put an end to the
      intolerable supremacy of medicine over surgery and contributed to the promotion
      of surgery. In 1743, he was the first to give a valid description of the disease
      that bears his name.

PMID- 12189773
TI  - Meta-analysis of flecainide safety in patients with supraventricular arrhythmias.
AB  - Flecainide (CAS 54143-55-4) has been associated with increased mortality in
      patients with ventricular dysfunction and arrhythmias. It is a potent suppressant
      of supraventricular arrhythmias, but safety data for use in this condition are
      rare. A meta-analysis was performed including 122 prospective studies on the use
      of flecainide in patients with supraventricular arrhythmias and no significant
      signs of ventricular damage. 4811 patients on flecainide were included (mean age
      55 +/- 13 years, 60% male). 38 studies were on i.v. Flecainide, 84 on p.o.
      application, 21 were placebo-controlled, 37 were comparative studies with other
      antiarrhythmics. The total exposure time was 2015 patient years, with a mean
      flecainide dose in p.o. studies of 216 +/- 65 mg/day. The total database on
      flecainide contains the reports of 8 deaths (total mortality 0.166%, mortality
      rate per 100 patient years 0.397). 3 deaths were non-cardiac deaths (cancer,
      suicide, urosepsis). Of the cardiac deaths, all but two occurred in patients with
      coronary heart disease. In controls, there was 1 death. Even for all deaths, this
      difference was not significant (p = 0.46). Proarrhythmic events were seen in 120
      patients on flecainide, and, significantly more frequent, in 88 control patients
      (p < 0.001). The data clearly show that the use of flecainide in patients with
      supraventricular arrhythmias is safe and, because of its proven efficacy,
      advisable. Scrutiny should be exercised to diagnose all patients with structural
      left ventricular damage.

PMID- 12189774
TI  - Local treatment of hemorrhoidal disease and perianal eczema. Meta-analysis of the
      efficacy and safety of an Escherichia coli culture suspension alone or in
      combination with hydrocortisone.
AB  - The objective of this paper was to assess the available clinical data on the
      efficacy and safety of ointments containing either a bacterial culture suspension
      (BCS) from Escherichia coli or a combination of BCS with hydrocortisone (CAS 50
      23-7) (BCS: Posterisan, and BCS + HC: Posterisan forte). The BCS is assumed to
      act by immunomodulation in hemorrhoidal disease and perianal eczema. Six
      randomized, double-blind trials are reported: three of them using BCS ointment
      and one using BCS + HC, against ointment base, and two trials using BCS + HC
      against hydrocortisone ointment alone. Patients with hemorrhoids and/or perianal
      eczema were included and treated over 2 weeks with weekly assessments. Efficacy
      parameters included score changes for burning, itching, redness and soiling as
      well as the investigators' overall efficacy rating. Safety was assessed from
      adverse drug reactions and an overall safety rating. Out of 1,070 patients (mean
      age 50 years), 273 received BCS and 229 BCS + HC; 568 patients were given the
      various controls. In the overall efficacy rating, BCS ointment was significantly
      superior to the ointment base in all three studies (p = 0.028, p = 0.016, and p =
      0.045). Moreover, BCS + HC was superior to the ointment base (p < 0.001) and to
      hydrocortisone alone (p = 0.156 and p = 0.021), confirming the distinct effect of
      the E. coli suspension. Satisfactory results were achieved in 83% of patients
      after the BCS + HC combination, 77% after BCS-containing ointment, 75% after
      hydrocortisone ointment and 52% after ointment base. Symptom scores decreased
      consistently more after administration of BCS than after the ointment base (p =
      0.095, p = 0.006, and p = 0.029), and likewise, the combination of BCS + HC was
      significantly superior to the ointment base (p < 0.001) and to hydrocortisone
      alone (p = 0.036 and p = 0.019). Adverse events were less frequent for BCS and
      BCS + HC than for the ointment base. It can therefore be concluded that ointments
      containing either only E. coli BCS or a combination of BCS and hydrocortisone
      provide significant relief in perianal eczema as well as in early stages of
      hemorrhoidal disease.

PMID- 12189775
TI  - Reproductive toxicity of gamma-ethyl-gamma-phenyl-butyrolactone, a new
      anticonvulsant and hypnotic drug, in mice. Fertility and peri- and post-natal
      studies.
AB  - The reproductive toxicity of gamma-ethyl-gamma-phenyl-butyrolactone (EPBL, CAS
      53380-21-5), a new anticonvulsant and hypnotic drug, was investigated by
      performing fertility and peri- and post-natal studies in mice. In both studies,
      EPBL was administered by gavage at 0, 50, 10, or 200 mg/kg doses. The first study
      found parent toxicity as measured by reduced body weight at the higher dose. At
      the same dose, the number of live fetuses was decreased. However, neither male or
      female fertility nor the reproductive performance of mice were affected. The
      results of the second study showed that the only negative effects were a
      depression of maternal weight gain and a decrease in body weight of the litter at
      birth which was 200 mg/kg. A reduction in the survival rate was also seen. There
      was no evidence that treatment of F0 females from day 15 of pregnancy to day 21
      post-partum affected either the reproductive capacity of the F1 offspring or the
      development of F2 progenies. The non observed effects levels (NOEL) for both
      studies can be estimated at 100 mg/kg.

PMID- 12189776
TI  - A randomised, placebo-controlled study comparing two formulations of
      dimenhydrinate with respect to efficacy in motion sickness and sedation.
AB  - It is known that sedation by H1 antihistaminic drugs can be reduced or avoided if
      slow release formulations are used for their administration, probably because of
      a slower increase of the drug concentration in plasma and brain. The aim of this
      study was to compare two different formulations of dimenhydrinate (CAS 523-87-5),
      a single fast release tablet with three chewing gums (divided dose principle),
      with regard to their efficacy in a motion sickness model and their detrimental
      effect on vigilance and central nervous system (CNS) performance. Caloric
      stimulation of the eardrum (air at 44 degrees C) was used to induce the symptoms
      of motion sickness in 24 symptomatic volunteers in a three-way cross-over design
      comparing three chewing gums (Superpep forte, chewed for 30 min each) containing
      20 mg dimenthydrinate each with a 50 mg dimenhydrinate tablet and placebo. During
      caloric stimulation the following parameters were measured in order to compare
      efficacy: Quantitative analysis of sodium excretion by sweat (main target
      parameter), subjective well being (vertigo) by visual analogue scales (VAS) and
      frequency of binocular nystagmus by computer nystagmography. Unwanted effects on
      vigilance and CNS performance were measured by means of the N1-P2 peak to peak
      amplitudes of auditory evoked potentials (AEPs) as an objective, quantitative
      parameter of vigilance and the latency to correct responses and the number of
      correct responses (complex choice reaction task) in the oculodynamic test (ODT)
      as parameters of complex choice reaction ability. As a main efficacy result
      sodium excretion by sweat was markedly reduced by the chewing gums and by the
      tablet. The differences to placebo were highly significant (chewing gums vs.
      placebo p < 0.0001, tablet vs. placebo p < 0.0001). There was no relevant and no
      significant difference between both medications (p = 0.308). The secondary
      efficacy parameters, frequency of binocular nystagm and the VAS vertigo were
      markedly reduced by both medications in comparison to placebo, i.e. both
      medications were markedly effective. In both cases, however, this result failed
      statistical significance. The unwanted depressing effects on vigilance and CNS
      performance of the chewing gums were less pronounced than that of tablets. The
      N1/P2 peak-to-peak amplitudes of the AEPs were significantly reduced by both the
      chewing gums and the tablets. The effect of the tablets was, however, larger than
      that of the chewing gums. This highly significant (tablet vs. chewing gums, p =
      0.0003) difference shows that the tablet had a larger depressing effect on
      vigilance (greater sedation). In line with this result, the number of correct
      responses in the ODT was markedly and significantly reduced by the tablet (p =
      0.0027) but not significantly by the chewing gums (p = 0.8140). The difference
      between the tablet and the chewing gums was highly significant (p = 0.0052). The
      complex choice reaction time was markedly and nearly significantly (p = 0.0558)
      prolonged by the tablet whereas the chewing gums produced only a very small and
      insignificant prolongation. That the objective measurements of vigilance and CNS
      performance showed significantly larger detrimental effects of the tablet than of
      the chewing gums is probably a consequence of a faster increase of the
      dimenhydrinate concentration in the CNS after administration of the tablet in
      comparison to the divided dose principle of the chewing gums.

PMID- 12189777
TI  - Synthesis and calcium channel antagonist activity of 1,4-dihydropyridine
      derivatives containing 4-nitroimidazolyl substituents.
AB  - Alkyl, cycloalkyl and arylakyl ester analogues of nifedipine (CAS 21829-25-4), in
      which the ortho-nitro phenyl group at position 4 is replaced by 1-methyl-4-nitro
      5-imidazolyl substituent, were synthesized and evaluated as calcium channel
      antagonists using the high K+ contraction of guinea-pig ileal longitudinal smooth
      muscle. The results for the symmetrical esters showed that increasing the length
      of methylene chain in C-3 and C-5 ester substituents for more than two methylene
      units (n > 1) decreases activity. In the phenylalkyl ester series increasing the
      length of methylene chain increases activity. In the series of unsymmetrical
      phenylalkyl esters (R2 = Me or Et) increasing the length of the methylene chain
      decreases activity. The results demonstrate that most of the compounds had
      similar activity to the reference drug nifedipine. Among symmetrical diesters
      (methyl, ethyl and phenylpropyl derivatives) and among unsymmetrical series
      (benzyl methyl, benzyl ethyl and phenethyl ethyl derivatives) were more active
      than the reference drug nifedipine. The unsymmetrical phenethyl ethyl derivative
      was the most potent antagonist tested. The structure-activity data indicate that
      the 4-(1-methyl-4-nitro-5-imidazolyl) moiety, bioisoester of 2-nitro-phenyl
      moiety, is as good as other nitro-imidazolyl moieties.

PMID- 12189778
TI  - Studies on the cardiotoxicity of noradrenaline in isolated rabbit hearts.
AB  - The concentration-dependent toxic effects of exogenous noradrenaline (NA, CAS 51
      41-2) on acute regional myocardial ischemia (MI) was investigated with and
      without alpha- and beta-adrenoceptor blockade. Electrically-driven rabbit
      Langendorff-hearts with depleted catecholamine stores were used (reserpin 7.0
      mg/kg i.p. 16-24 h before preparation, constant pressure: 70 cm H2O, Tyrode
      solution, Ca2+ 1.8 mmol/l). Repetitive MI, separated by a reperfusion period of
      50 min, was induced by coronary artery branch ligature, and quantitated from
      epicardial NADH-fluorescence photography. Starting after a reperfusion period of
      20 min, hearts were treated with exogenous NA (10(-7), 10(-6) or 10(-5) mol/l).
      Adrenoceptors were blocked by propranolol (10(-6) mol/l) and phentolamine (10(-6)
      mol/l). Without adrenoceptor blockers, NA 10(-6) mol/l induced an increase in
      left ventricular pressure and a reduction in the relative coronary flow.
      Concomitantly, MI was enhanced. After adrenoceptor blockade, NA 10(-7) or 10(-6)
      mol/l had no influence on functional parameters. MI was not affected by NA 10(-7)
      mol/l, but MI was significantly enhanced by NA 10(-6) mol/l. MI enhancement by NA
      10(-6) mol/l was completely prevented by superoxide dismutase (30 U/ml).
      Functional effects of NA 10(-5) mol/l were not completely inhibited by
      adrenoceptor blockers at the concentrations used, and arrythmias were observed.
      MI was also enhanced by NA 10(-5) mol/l. CONCLUSION: Deleterious effects on MI,
      that are independent on functional effects, are induced by NA in a micromolar
      concentration. These direct toxic effects are mediated by superoxide anion
      radicals. In lower concentrations (10(-7) mol/l), there is no evidence for direct
      toxic actions of NA independent of functional effects. MI enhancement by NA 10(
      5), or 10(-6) mol/l without adrenoceptor blockers may have been caused in part by
      functional and arrythmogenic effects and/or through the generation of oxygen free
      radicals.

PMID- 12189779
TI  - Haemodynamic and metabolic effects of low daily dose sulphonylureas in diabetic
      dog hearts.
AB  - The effects of glibenclamide (GB, CAS 10238-21-8) and those of the latest low
      daily dose sulphonylurea compound, glimepiride (GM, CAS 93479-97-1) on myocardial
      haemodynamics and pyruvate-lactate metabolism of healthy and alloxan-diabetic
      dogs (n = 6 in six groups) were compared. Mean arterial blood pressure, heart
      rate, blood flow of the left anterior descending coronary artery, myocardial
      contractile force, the rate of change of myocardial contraction and relaxation
      were measured and arterial (a. carotis communis) and venous (sinus coronarius)
      pyruvate and lactate concentrations were determined during i.v. administration of
      the drugs (0, 0.4, 2, 5, and 8 mumol/kg). Coronary conductivity, pressure-rate
      product and pyruvate-lactate extraction rates were calculated. Glimepiride
      reduced the heart rate in diabetic animals. Both compounds decreased myocardial
      contractile force, coronary blood flow and conductivity and the rate of change of
      myocardial contraction. However, alterations in blood pressure, pressure-rate
      product, the rate of change of myocardial relaxation and arterio-venous lactate
      difference elicited by glibenclamide proved to be more expressed than those by
      glimepiride. According to the results, glibenclamide and especially glimepiride
      do not enhance the disturbances of the cardiovascular system in diabetes. By this
      reason, considering its very low daily dose and favourable haemodynamic effects,
      glimepiride could preferably be recommended for the treatment of type 2 diabetics
      with coronary heart disease.

PMID- 12189780
TI  - HPLC method for the determination of rosiglitazone in human plasma and its
      application in a clinical pharmacokinetic study.
AB  - Rosiglitazone (CAS 155141-29-0, Avandia) is a novel insulin sensitizer used in
      the treatment of type 2 diabetes. A sensitive high performance liquid
      chromatography (HPLC) method for its determination in human plasma using
      fluorescence detection (excitation: 247 nm, emission: 367 nm) with a suitable
      internal standard (I. S.) is described. Ethyl acetate was used as extraction
      solvent. A mobile phase consisting of phosphate buffer, acetonitrile and methanol
      was used at a flow rate of 1.0 ml/min on a C18 column. The absolute recovery was
      > 90% and the lower limit of quantitation was 5 ng/ml. The intra- and inter-day
      relative standard deviations ranged from 0.58-6.69% and 0.82-6.63%, respectively.
      The method described is simple, economical, precise and accurate and has been
      successfully applied in a pharmacokinetic study conducted in healthy human
      volunteers.

PMID- 12189781
TI  - Synthesis and antituberculosis activity of cycloalkylidenehydrazide and 4-aza-1
      thiaspiro[4.5]decan-3-one derivatives of imidazo[2,1-b]thiazole.
AB  - New N2-cycloalkylidene-(6-phenyl/4-chlorophenylimidazo[2,1-b]thiazol-3-yl) acetic
      acid hydrazides (2a-h and 3a-b) were synthesized by reacting (6-phenyl/4
      chlorophenylimidazo[2,1-b]thiazol-3-yl)acetic acid hydrazides with cyclohexanones
      or cyclopentanone. Furthermore, 2a-h were refluxed with thioglycolic or
      thiolactic acid to give 4-[[(6-phenyl/4-chlorophenylimidazo[2,1-b]thiazol-3-yl)
      acetyl]amino]-4-aza-1-thiaspiro[4.5]decan-3-ones (4a-h and 5a-h). The structures
      of the title compounds were established by spectral data (IR, 1H-NMR, 13C-NMR and
      EIMS (Electron Impact Mass Spectrometry)) and elemental analysis. The synthesized
      compounds were evaluated for antituberculosis activity against Mycobacterium
      tuberculosis H37Rv (ATCC 27294). The compounds exhibited varying degrees of
      inhibition in the in vitro primary screening that was conducted at a
      concentration of 6.25 micrograms/ml against M. tuberculosis H37Rv (ATCC 27294) in
      Bactec 12B medium using the Bactec 460 radiometric system or a broth
      microdilution assay, the Microplate Alamar Blue Assay (MABA). Compounds 2f, 2h,
      3b, 4a, 4c, 4d, 5a-e and 5h demonstrating at 1-east 90% inhibition in the primary
      screen were re-tested at lower concentrations against M. tuberculosis H37Rv (ATCC
      27294) to determine the actual minimum inhibitory concentration (MIC) using MABA.
      The most active compounds were found to be 4d and 5c. The structure-activity
      relationships of the derivatives were investigated.

PMID- 12189782
TI  - Synthesis and antifungal and antioxidant properties of some new 5-substituted-4
      amino(or aryl)-3-mercapto-4(H)-1,2,4-triazoles.
AB  - The synthesis and antifungal and antimicrobial evaluation of some new 5
      substituted-4-amino(or aryl)-3-mercapto-4(H)-1,2,4-triazoles is reported. The
      involvement of the new compounds in free radical processes is also investigated
      and their lipophilicity is calculated and related to the determined antioxidant
      activity. Compounds 7a, 7b and 7c exhibited interesting antioxidant properties at
      concentration 0.01 mmol/l, expressed by their capacity to inhibit Fe2+/ascorbate
      induced hepatic microsomal lipid peroxidation, to scavenge OH.and to interact
      with nitrogen centered radicals such as 1,1-diphenyl-2-picrylhydrazyl stable free
      radical (DPPH). Moreover, compound 6a showed activity against Aspergillus
      versicolor, possessing a MIC of 82 micrograms/ml.

PMID- 12189783
TI  - Inquilines of Brachymenes dyscherus nests with special reference to Monobia
      schrottkyi (Hymenoptera, Vespidae, Sphecidae).
AB  - Sixty-four inactive nests of the solitary mud-daubing wasp Brachymenes dyscherus,
      reused by 5 inquiline species, were collected at Fazenda Santa Carlota, Cajuru,
      Sao Paulo, Brazil in 1995 and 1996. Monobia schrottkyi used 52 nests; among the
      717 cells available for use, 502 were reused. The number of cells per nest varied
      from 3 to 24; 1 to 16 individuals emerged from September to April (154 males and
      112 females). Forty-six cells were parasitized by Melittobia sp. (n = 44) and
      Ichneumonidae (n = 2). Monobia curvata used 3 nests; among the 50 cells available
      for use, 38 were reused and 15 males and 8 females emerged from August to
      November. Three cells were parasitized by Ichneumonidae. Montezumia petiolata
      occupied 1 nest; among the 8 available cells, 7 were reused and 2 males and 3
      females emerged in September. Podium denticulatum used 2 nests; the 20 cells
      available for use were reused and 11 males and 4 females emerged in August.
      Trypoxylon rogenhoferi used 5 nests that had 65 available cells; 48 of them were
      reused, from which 19 males and 11 females emerged from September to November.
      Three cells were parasitized by Ichneumonidae (n = 2) and Chrysididae (n = 1).

PMID- 12189785
TI  - [New species of bees of Cuba and La Espanola (Hymenoptera: Colletidae,
      MEgachilidae, Apidae)].
AB  - Five new species of Antillean bees are described and illustrated: Colletes
      granpiedrensis n. sp. (Cuba) (Colletidae) is characterized as follows: Head and
      mesosoma black, legs and metasoma brown. Dense brown hairs on head and mesosoma;
      white on frons and metasomal terga. Clypeus, frons and mesosoma with large
      punctures, lesser on vertex and metasoma. Malar space more wide than long. Male
      and female slightly similar, except in the apical margin of clypeus, supraclipeal
      area, and color of the pubescence on legs and sterna; Osmia (Diceratosmia)
      stangei n. sp. (Dominican Republic) (Megachilidae) is characterized as follows:
      Dark metallic green, metasoma black with metallic green reflections. Pubescence
      light; body with large, closed punctures. Female with violet reflections in
      tergum III and mandible tridentate; Coelioxys (Cyrtocoelioxys) alayoi n. sp.
      (Cuba) (Megachilidae) is characterized as follows: Female black, except basal
      area of mandibles, tegula, legs, lateral area of tergum I and sterna, reddish
      brown. Posterior margin of scutellum rounded. Apex of tergum VI with spine curved
      up. Sternum VI fringed with short, closed setae, and the apex with short spine;
      Coelioxys (Boreocoelioxys) sannicolarensis n. sp. (Cuba) (Megachilidae) is
      characterized as follows: Black, except antenna and tegula brown; legs and sterna
      reddish brown. Clypeal margin straight in profile. Gradular grooves on metasomal
      terga II and III distinct medially. Fovea on metasomal tergum II of male deep and
      short, and Triepeolus nisibonensis n. sp. (Dominican Republic) (Apidae) is
      characterized as follows: Dorsal pubescence (short and dense) on mesosoma and
      metasoma from white to yellow, according to specimen; ventral pubescence white.
      Tergal bands of hairs interrupted medially; two spots of light pubescence on
      tergum II. Male metasomal sternum VII with anterior margin V-shaped and basal
      constriction narrow.

PMID- 12189784
TI  - [Insects associated with flowers of weeds of the Botanical Garden of Santiago de
      Cuba, with emphasis on Hymenoptera].
AB  - The insect visitors of flowers in nine weeds species were studied in the
      Botanical Garden of Santiago de Cuba, Eastern Cuba, during 1993 (March-June,
      spring season) and 1994 (January-March, end of winter and beginning of spring
      season). About 50 hours of collecting efforts were made at three times (0900-0930
      hr in 1993; 0900-0930 hr, 1200-1230 hr and 1500-1530 hr in 1994). More than 140
      species of at least 37 families were found; Hymenoptera dominated (with more than
      a half of specimens), followed by Diptera, Coleoptera and Lepidoptera. Among
      Hymenoptera, bees (Apoidea) were the largest group, especially Apis mellifera L;
      followed by wasps (Vespidae, Pompilidae, Sphecidae) and ichneumon flies
      (Ichneumonidae); Microhymenopterans were not sampled. Hymenopterans of each weed
      were compared for diversity, similarity, dominant and subdominant species,
      visitation time, sampling efficiency, etc. Each plant species had a particular
      Hymenoptera complex, almost one third of which were natural enemies of
      agricultural pests, and most are believed to be potential pollinators. Closely
      related species showed similar patterns of daily activity, with a peak at 0900
      0930 hr for all plant species. Second grade polynomial equations were the best
      fitted models to describe the relationships between number of species and number
      of specimens, and between total number of species and number of samples (R2 =
      0.9734 and R2 = 0.9573, p < 0.01). The role of weeds in the biodiversity of the
      agroecosystems is analyzed; as well as the effectiveness of this collection
      method to study Hymenoptera.

PMID- 12189786
TI  - A key to the adult Costa Rican "helicopter" damselflies (Odonata:
      Pseudostigmatidae) with notes on their phenology and life zone preferences.
AB  - We present a key to the Costa Rican species of Pseudostigmatidae, comprising
      three genera with the following species: Megaloprepus caerulatus, Mecistogaster
      linearis, M. modesta, M. ornata and Pseudostigma aberrans. Pseudostigma accedens,
      which may occur in the region, is also included. For each species we give a brief
      account of morphology, phenology and life zone preferences, including
      distributional maps based on more than 270 records. These are not all of the
      known specimens from the area, but a high enough number to give a relatively good
      picture of the distribution and status of the species. We found M. caerulatus to
      be active during the first half of the year in seasonal, tropical semi-dry
      lowland forest and tropical moist forest at mid-elevation, but like M. linearis,
      M. caerulatus was active all year round in non-seasonal, tropical wet lowland
      forest and tropical moist forest at mid-elevation. Mecistogaster modesta also
      flew year round in non-seasonal, tropical wet lowland forest and tropical moist
      evergreen forest at mid-elevation, and likewise in seasonal and non-seasonal,
      tropical premontane moist forest. Only a few findings, however, have been made of
      M. modesta in seasonal, tropical semi-dry deciduous forest and seasonal, tropical
      moist evergreen forest. Mecistogaster ornata was missing entirely from non
      seasonal, tropical wet lowland forest and non-seasonal, tropical moist forest at
      mid-elevation, while this species was active year round in seasonal, tropical dry
      lowland forest and tropical semi-dry forest, as well as in seasonal, tropical
      moist evergreen forest and tropical premontane moist forest, both at mid
      elevation. Pseudostigma aberrans has so far been found too few times in Costa
      Rica for any indication of flight time preference.

PMID- 12189787
TI  - A survey of homopteran species (Auchenorrhyncha) from coffee shrubs and poro and
      laurel trees in shaded coffee plantations, in Turrialba, Costa Rica.
AB  - A survey of homopteran species (Auchenorryncha) was conducted in coffee
      plantations with no shade (C), and in those with shade of either poro (Erythrina
      poeppigiana) (CP) or poro plus laurel (Cordia alliodora) (CPL), in Turrialba,
      Costa Rica. A total of 130 species in ten families were collected, dominated by
      Cicadellidae (82 species). Species richness was highest in the CP system (88),
      followed by CPL (74) and C systems (60). Five most common species for all systems
      were Fusigonalia lativittata, Hebralebra nicaraguensis, Neocoelidia sp., Oliarus
      sp. and Clastoptera sp. Diversification of the coffee agroecosystem favors some
      species while limiting others, and have no effect on the majority of species.
      Thus, only F. lativittata, Neocoelidia sp. and Scaphytopius ca. latidens were
      well represented in all systems, but were more abundant in coffee shrubs.
      Additionally, the following were the dominant species in each system:
      Graphocephala sp. 1 (C), F. lativittata (CP) and H. nicaraguensis (CPL). Four
      species abundant on laurel trees, including H. nicaraguensis, appeared almost
      exclusively on these tree species. Species similarity was highest on the CP and
      CPL systems (51% of the species in common), followed by the C and CP (39%) and
      the C and CPL systems (38%). These findings show that even disturbed systems can
      harbor many insect species, so that they deserve attention from conservation
      advocates and biologists.

PMID- 12189788
TI  - [Reproductive activity of Coelomera lanio (Coleoptera: Chrysomelidae)].
AB  - The Cecropia spp. (Cecropiaceae) trees are attacked by several insects; among
      them, Coelomera lanio (Dalman) (Coleoptera: Chrysomelidae). The reproductive
      behavior of C. lanio was studied under laboratory conditions (12 hour
      photoperiod, 24.1 +/- 0.1 degrees C and mean relative humidity 67.7 +/- 0.6%), in
      Vicosa, Minas Gerais, Brazil. The insects were reared in cages and in Petri
      dishes and fed leaves of Cecropia pachystachya Trec. Reproductive activity began
      5.8 +/- 0.2 days after adult emergence and mean copulation time was 2.5 +/- 0.1
      min. The female began oviposition only after 25.7 +/- 0.7 days. Each female laid
      a mean of 4.7 +/- 0.4 times (range 1-9). The mean number of eggs per oviposition
      and female was 129.2 +/- 2.4 and 587.4 +/- 92.1 respectively, and the time
      between egg-layings averaged 16.3 +/- 0.8 days.

PMID- 12189789
TI  - Lepidoptera pests collected in Eucalyptus urophylla (Myrtaceae) plantations
      during five years in Tres Marias, State of Minas Gerais, Brazil.
AB  - Lepidoptera pest species from eucalyptus were collected in Eucalyptus urophylla
      plantations in the region of Tres Marias, State of Minas Gerais, Brazil, every 15
      days from June 1989 to June 1994 with five light traps. Twelve primary and 15
      secondary pest species were collected in the period with an average of 13,387 and
      812 individuals per light trap, respectively. Most collected primary pest species
      were Stenalcidia grosica (Geometridae), Iridopsis subferaria (Geometridae),
      Eupseudosoma aberrans (Arctiidae) and Psorocampa denticulata (Notodontidae),
      totalizing for the study period an average of 5,450, 2,162, 2,436 and 1,458
      individuals per light trap, respectively. Idalus admirabilis (Arctiidae) was the
      most collected secondary pest species, averaging 652 individuals/trap. Most
      primary pest species were collected during the dry season, from April to July,
      whereas most secondary pest species were collected during the rainy season, from
      January to March. These differences on seasonal occurrence between the two groups
      could be due to the fact that many secondary pest species of Eucalyptus in Brazil
      pupate in the soil, and they need humidity to complete its pupal stage.

PMID- 12189790
TI  - [A new species of frog of the genus Hyalinobatrachium (Anura: Centrolenidae) of
      the Delta of the Orinoco River, Venezuela].
AB  - A new species of Hyalinobatrachium of the fleischmanni group, H. mondolfii, is
      described from the Orinoco delta floodplains in Venezuela. This new species can
      be distinguished from other congeners by the following combination of characters:
      parietal peritoneum clear, pericardium white, visceral and hepatic peritoneum
      white, color in life pale green with diminute yellow spots and, in preservative,
      cream with small dark melanophores (visible only under magnification), bones
      white in life, extense webbing, snout round in dorsal view and inclinate in
      lateral view, dorsal skin granulate and a advertisement call with a fundamental
      frequency greater than 5000 Hz.

PMID- 12189791
TI  - Distribution and abundance of four caiman species (Crocodylia: Alligatoridae) in
      Jau National Park, Amazonas, Brazil.
AB  - Jau National Park is a large rain forest reserve that contains small populations
      of four caiman species. We sampled crocodilian populations during 30 surveys over
      a period of four years in five study areas. We found the mean abundance of caiman
      species to be very low (1.0 +/- 0.5 caiman/km of shoreline), independent of
      habitat type (river, stream or lake) and season. While abundance was almost
      equal, the species' composition varied in different waterbody and study areas. We
      analysed the structure similarity of this assemblage. Lake and river habitats
      were the most similar habitats, and inhabited by at least two species, mainly
      Caiman crocodilus and Melanosuchus niger. However, those species can also inhabit
      streams. Streams were the most dissimilar habitats studied and also had two other
      species: Paleosuchus trigonatus and P. palpebrosus. The structure of these
      assemblage does not suggest a pattern of species associated and separated by
      habitat. Trends in species relationships had a negative correlation with species
      of similar size, C. crocodilus and P. trigonatus, and an apparent complete
      exclusion of M. niger and P. trigonatus. Microhabitat analysis suggests a slender
      habitat partitioning. P. trigonatus was absent from river and lake Igapo (flooded
      forest), but frequent in stream Igapo. This species was the most terrestrial and
      found in microhabitats similar to C. crocodilus (shallow waters, slow current).
      Melanosuchus niger inhabits deep, fast moving waters in different study areas.
      Despite inhabiting the same waterbodies in many surveys, M. niger and C.
      crocodilus did not share the same microhabitats. Paleosuchus palpebrosus was
      observed only in running waters and never in stagnant lake habitats. Cluster
      analysis revealed three survey groups: two constitute a mosaic in floodplains,
      (a) a cluster with both M. niger and C. crocodilus, and another (b) with only C.
      crocodilus. A third cluster (c) included more species, and the presence of
      Paleosuchus species. There was no significant difference among wariness of
      caimans between disturbed and undisturbed localities. However, there was a clear
      trend to increase wariness during the course of consecutive surveys at four
      localities, suggesting that we, more than local inhabitants, had disturbed
      caimans. The factors that are limiting caiman populations can be independent of
      human exploitation. Currently in Amazonia, increased the pressure of hunting,
      habitat loss and habitat alteration, and there is no evidence of widespread
      recovery of caiman populations. In large reserves as Jau without many
      disturbance, most caiman populations can be low density, suggesting that in
      blackwater environments their recovery from exploitation should be very slow.

PMID- 12189792
TI  - [A new species of snake of the genus Sibon (Serpentes: Colubridae) of the
      Caribbean slope of Costa Rica].
AB  - Sibon lamari, a new species of colubrid snake from northeastern Costa Rica is
      described on the basis of six specimens. The new form differs from the closely
      allied S. annulatus in color pattern, head size, subcaudal count, and number of
      labials bordering eye-orbit. This is the third species of Sibon, together with S.
      argus and S. longifrenis, possessing a green dorsal ground color in Costa Rica.
      Sibon lamari coexists sympatrically with S. annulatus, S. argus. S. longifrenis
      and S. nebulatus at the locality of Guayacan de Siquirres (Limon Province).

PMID- 12189793
TI  - [Ultrastructure of the eggshell of hatched and non hatched eggs of Kinosternon
      angustipons (Testudinata: Kinosternidae)].
AB  - The ultrastructure of eggshells of Kinosternon angustipons is described and
      compared with the ones of K. leucostomum and K. scorpoides. Four eggs from
      captive turtles (30 sections) were studied with Scanning Electron Microscopy
      (SEM). the shell has three layers, cuticle or external, calcereous or
      intermediate and testacean or internal. Hatched and non-hatched eggs have similar
      characteristics in their external surface: fanned units and proteic fibers
      superposed at random. They differ in the presence of spongelike structures and
      more external porosity in non-hatched eggs. The intermediate and testacean layers
      of the hatched eggs have lance point like spaces and are thin in the proteic
      fibers. The ultrastructural evidence shows that during the embryonic development
      the thickness of the peal decreases. Non-hatched K. angustipons shells are
      thicker than in the other two kinosternon species of costa Rica.

PMID- 12189794
TI  - [Distribution of aquatic and raptor birds in a freshwater artificial pond of Baja
      California Sur, Mexico].
AB  - We determined the taxonomic composition and spatial-temporal distribution of
      aquatic and raptor birds in a freshwater artificial pond of El Centenario, Baja
      California Sur, Mexico, during 24 biweekly censuses (April, 1998 to March, 1999).
      The pond is particularly attractive for birds because of its variety of food
      items. A total 25,563 records of 69 species were done, among them the first
      report of Chlidonias niger and Phalaropus tricolor for the region. Species
      richness and abundance were determined for the migrant component, mostly Anatidae
      (16 species and 55.6% of the total abundance) and shorebirds (18 species and
      13.3%). The greater number of species and individuals was in C the deepest and
      more heterogeneous section of the pond. The most important species was Oxyura
      jamaicensis (30% of the total observed individuals), with highest abundance in
      the peninsula. The artificial pond presented an atypical and distinct
      ornithological composition because it is located in an arid region, and acts as a
      resting site for migrant birds. The site included species that usually live in
      freshwater and coastal areas, a characteristic reflected in their high richness.
      It contributes noticeably to the local avian biodiversity.

PMID- 12189795
TI  - [Reproduction of the bird Mimus gilvus (Passeriformes: Mimidae) in Maracaibo,
      Venezuela].
AB  - Four pairs of the poorly understood tropical mockingbird Mimus gilvus were
      captured and color banded at a grassland in Maracaibo, Venezuela in June 1997.
      Throughout the following 8 months, individuals were observed two days per week
      for 4 hours each. We recorded courtship behaviour, nest construction, incubation,
      parental care, territory defense and timing of reproductive cycle. Pairs lived in
      defined territories defended primarily by the male. Both sexes participated in
      nest building which began at the start of two rainy seasons: April and October.
      Between April and June, 80% of nests were parasited by the shiny cowbird
      (Molothrus bonariensis). No parasitism was recorded in the later nesting season.
      Consequently, breeding success for the April and October seasons was 20% and 83%
      respectively. Only the female incubated and the mean clutch size was 2.2 eggs.

PMID- 12189796
TI  - [The feral pig (Sus scrofa, Suidae) in Cocos Island, Costa Rica: composition of
      its diet, reproductive state and genetics].
AB  - Feral pigs (Sus scrofa) cause different kinds of damage specially on oceanic
      islands. Pigs were introduced at Cocos Island, Costa Rica, during 1793 and bred
      successfully. I analyzed feral pigs diet, reproductive state, genetics and the
      effects of predation, in order to gather data on their ecology and impact on
      certain Cocos Island communities. The diet was studied, during a dry and a wet
      period, through stomach contents. The genetic variability was determined through
      PCR analysis on tissue samples which were taken from feral (Cocos Island) and
      domestic (mainland) pig ear-lobes. Pigs at Cocos were omnivorous, the most
      important diet category in both seasons was fruits. More pigs consumed fruits
      during the wet season but the fruits did occupy more somuch volume during the dry
      season. Feral pigs did not disperse exotic seeds nor prey on animal endemic
      species. 56% of the hunted pigs were males and 44% were females. From females in
      reproductive age, 46% were pregnant or suckling, and the average number of
      fetuses in a litter was 4.4. I confirmed a reproductive peak during
      January/February but could not demonstrate a reproductive peak during June/July.
      The low fetuses number per litter could be related with some levels of stress.
      The genetic variability for all the evaluated parameters within the feral
      population was low but not as low as expected. I suggest a compensatory mechanism
      were the inbreeding depression reduces consanguinity and a species susceptible to
      stocastic, demographic or environmental factors turns to be an adapted species
      with high resilience.

PMID- 12189797
TI  - [The feral pig (Sus scrofa, Suidae) in Cocos Island, Costa Rica: Rootings, soil
      alterations and erosion].
AB  - Feral pigs (Sus scrofa) are of the most damaging exotic vertebrates, specially on
      oceanic island native communities. Feral pigs inhabit Cocos Island since 1793 and
      there are around 400-500 individuals. In order to quantify the impacts of the
      feral pigs at Cocos Island. I calculated the effect of the rooting activity and
      its influence on the natural erosion. During one year I walked, monthly, 15 km on
      trails estimating rooted area by transect and rooting recurrence. During eight
      months I compared erosion rates with and without rootings. I estimated the annual
      rooting rate between 10 and 20% of the total island surface. The rooted area was
      the only measured variable which correlated with the soil erosion rate. The
      erosion rate without rootings was 23.6 kg/ha/year and with rootings was 200.4
      kg/ha/year (P < 0.01). The disturbances provoked by the rootings were not
      scattered homogeneously through the island. The rootings, together with the
      natural landslides, dominate the soil disturbance pattern at Cocos Island. This
      study suggests that the presence of feral pigs produces more erosion than the one
      that would naturally occur without feral pigs at Cocos Island.

PMID- 12189798
TI  - [Annual follow-up of the gastrointestinal parasitosis of the tepezcuintle, Agouti
      paca (Rodentia: Agoutidae) in captivity in the Mexican tropic].
AB  - Previous reports showed that the tepezcuintle (Agouti paca) is commonly infested
      by gastrointestinal parasites (GIP), mainly Eucoccidiida and helminths. However,
      there is no available information on the frequency of those parasites and their
      faecal egg excretions at different moments during the year. These information
      would provide a valuable baseline for the establishment of control strategies
      against GIP in tepezcuintles under captivity. The objectives of the present study
      were to determine the prevalence of GIP orders and genera that infest
      tepezcuintles under captivity and, to describe the dynamics of faecal egg and
      oocyst excretion in a year. Ten tepezcuintles were sampled (faeces) twice every
      month for twelve months. The faecal samples were processed by the flotation and
      McMaster techniques. Two orders of parasites were determined: Strongylida and
      Eucoccidiida. Two genera of nematodes were also determined: Strongyloides and
      Trichuris. The prevalence of Strongylida eggs, Eucoccidiida oocysts and Trichuris
      sp. eggs reached 10-20% of animals in certain months. The most important genus
      was Strongyloides, found in 60 to 100% of the animals year round. The average
      excretion of eggs in the group was 45 to 372 eggs per gram. Tepezcuintles kept
      under captivity in Yucatan are parasited with Strongyloides sp throughout the
      year, but only occasionally had oocysts of Eucoccidiida and eggs of Strongylida
      and Trichuris sp.

PMID- 12189799
TI  - Swimming ability in three Costa Rican dry forest rodents.
AB  - We investigated the swimming abilities of three Costa Rican dry forest rodents
      (Coues' rice rat. Oryzomys couesi, hispid cotton rat, Sigmodon hispidus, and
      spiny pocket mouse, Liomys salvini) associated with a large marsh, Laguna Palo
      Verde, using 90 s swim trials in a plastic container. Swimming ability was
      evaluated by observing the use of limbs and tail in the water, inclination to the
      surface, and diving and floating behavior. Rice rats could float, swim and dive,
      suggesting that they can exploit surface and underwater resources. Cotton rats
      swam at the water's surface, but were less skilled swimmers than rice rats. Spiny
      pocket mice tired quickly and had difficulty staying at the water's surface.
      Results suggest that differential swimming ability is related to the distribution
      of the three sympatric species within the marsh and adjacent forest habitats.

PMID- 12189800
TI  - White-lipped peccary (Tayassu pecari, Artiodactyla: Tayassuidae) diet and fruit
      availability in a Costa Rican rain forest.
AB  - We studied fruit availability, diet and habitat use by white-lipped peccary
      (Tayassu pecari) in Corcovado National Park, southwest Costa Rica, from July 1996
      to April 1997. The results show that the availability of important fruits for the
      white-lipped peccary differs between habitats and climatic seasons. Fruit
      availability was highest in the primary forest than secondary and coastal forest.
      There was a period of shortage of fruits to ends of the wet season, during which
      the consumption of not seasonal resources like leaves and shafts increased. The
      important fruits during this period of shortage were Ficus sp and Licania
      operculipetala. The several types of forest were used according to the fruit
      availability, and it was a direct relation between the consumption and the fruit
      availability.

PMID- 12189801
TI  - [Feeding habits of raccoon (Procyon lotor) (Carnivora: Procyonidae) in a coastal,
      tropical wet forest of Costa Rica].
AB  - Raccoon (Procyon lotor) food habits were studied at Manuel Antonio National Park,
      a tropical rain forest in the Pacific coast of Costa Rica from May to December
      1987, from September to December 1989 and from January to April 1990. A 134 feces
      sample size was used to assess the most important items in raccoon diet: two crab
      species (Gecarcinus quadratus and Cardisoma crassum) with a relative frequency of
      0.94 in the rainy season of 1987, 0.76 in the rainy season of 1989 and 0.65 in
      the dry season of 1990. Fruits were the second category in importance, with
      relative frequencies of 0.09 for 1987, 0.32 for 1989 and 0.44 for 1990.

PMID- 12189802
TI  - White-faced monkey (Cebus capucinus) ecology and management in neotropical
      agricultural landscapes during the dry season.
AB  - Habitat use by a C. capucinus troop was studied in an agricultural landscape
      during late dry season (March-April 1994) in northwest Costa Rica. Riparian
      forests, palm canals and living fence rows accounted for 82% of observations,
      significantly more than the other six habitats present. The study troop consumed
      24 species of plants and five animals. Feeding concentrated on the introduced
      African oil palm (Elaeis guineensis) (33.6%) and mango (Mangifera indica)
      (27.2%), found mostly in palm canals and mango orchards respectively. The troop
      rested between 0930-1330 hr and fed and moved between 0530-0930 hr and 1330-1730
      hr. Living fence rows were used as travel routes or corridors and less
      intensively for other activities.

PMID- 12189803
TI  - Growth and survival of Escherichia coli O157: H7 in meat, poultry and vegetables
      mixed with different concentrations of mayonnaise.
AB  - In the last 20 years Escherichia coli O157: H7 has emerged as a new pathogen,
      causing worldwide disease, death and economic loss. Different studies have
      revealed important survival characteristics of this pathogen, although there are
      divergent criteria about its ability to survive in various mayonnaise
      formulations. We studied the effect of different mayonnaise concentrations (0%,
      18%, 37% and 56%) (weight/weight) over the survival of the bacterium in common
      foods from a neotropical environment (Costa Rica). High [10(7)-10(8) Colony
      Forming Units (CFU)/ml] and low E. coli populations (10(4)-10(6) CFU/ml) were
      inoculated, (three replicates) in meat, chopped cabbage and poultry, and mixed
      with commercial mayonnaise to obtain the concentrations specified. They were
      incubated at 12 degrees C for 24, 48 and 72 hr. The E. coli O157: H7 enumeration
      was done according to a standard methodology. Populations of E. coli O157: H7
      showed an increasing trend during the first incubation period (48 hr), in all the
      preparations, regardless of the fat concentration used. Our data indicate that E.
      coli O157: H7 is capable of surviving and growing in meat, cabbage and poultry
      mixed with mayonnaise, independently of its concentration.

PMID- 12189804
TI  - [In vitro evaluation of antibacterial substances produced by bacteria isolated
      from different marine organisms].
AB  - Bacteria from several groups of marine organisms were isolated and, using direct
      antibiograms, identified those that produce antibacterial substances, using a
      human pathogenic strain of Staphylococcus aureus ATCC6538 as revealing
      microorganism. Bacteria which produce substances that inhibited S. aureus growth
      were identified through morphological, physiological and biochemical tests. Out
      of 290 bacteria, 54 (18.6%) inhibited the growth of S. aureus, but only 27
      survived for identification. Bivalves, sponges and corals were the most
      represented from which 41.2, 33.3 and 29.7%, respectively, produced antibacterial
      substances of the isolated bacteria in each group. The marine species with
      highest proportions of these bacteria were the hard coral Madracis decactis
      (62.5%), the sponges Cliona sp. (57.1%) and the octocoral Plexaura flexuosa
      (50.0%). Out of the 27 strains that produced antibacterial substances, 51.8% were
      Aeromonas spp. and 14.8% Vibrio spp. Marine bacteria that produce antibacterial
      substances are abundant, most belong in the Vibrionacea group and were isolated
      mainly from corals and bivalve mollusks.

PMID- 12189805
TI  - [Human chromosome banding with raw extract of fruits or leaves of papaya].
AB  - One week old human chromosome preparations were treated with filtrate from one
      liquefied leaf (53 g) of papaya (Carica papaya) in 100 ml of distilled water, and
      stained with 1.5% Giemsa (pH 6.8). Good chromosome banding was obtained after 2
      min of treatment. Solutions that have been frozen even for years are effective
      and the method is cheaper and easier than others.

PMID- 12189806
TI  - [Cytogenetical prenatal diagnosis by amniocentesis during the II and III
      gestation trimesters in Costa Rica].
AB  - The identification of fetal abnormal chromosomes in high risk pregnancies allows
      proper pediatric and obstetric management of the cases as well as genetic
      counseling. The results of 842 genetic amniocentesis from 1986 to 1999 are
      reported. All procedures were performed transabdominally and under ultrasound
      guidance, in hospitals of the social security system and in private facilities.
      There were two main reasons for referral: abnormal ultrasound assessment (48% of
      cases) and advanced maternal age (35%). Most procedures (66%) were performed
      during the second trimester of pregnancy and 34% during the third trimester.
      Fetal cells were closed cultured and suspension harvested. Median turn around
      time was 14 days. In 217 amniotic fluid samples no diagnosis could be obtained,
      mainly due to absence of cell growth in late gestation samples or because of
      blood contamination. Of 625 fetal karyotypes 55 (9%) were abnormal, due to 33
      trisomies (including a Robertsonian translocation trisomy 13), eight cases of
      monosomy X, three mosaics (including a mosaic trisomy 22), balanced and
      unbalanced translocations, extra structurally abnormal chromosomes and other
      defects. Pseudomosaicism was detected in five cases. Taking into account the
      reason for referral, cases studied as a result of abnormal ultrasound assessment
      exhibited 17% abnormal karyotypes, in contrast to 2.5% cytogenetic defects in
      pregnancies of women 35 years or older. Prenatal cytogenetic and sonographic
      findings correlated with the phenotype of the newborn in 211 cases available for
      follow-up. Prenatal diagnosis of fetal defects allowed genetic counseling as well
      as better obstetric management and pediatric care. Normal results of both tests
      provided reassurance to prospective parents.

PMID- 12189807
TI  - [Analysis of various classical genetic markers in the Costa Rica population].
AB  - A study of several loci blood groups (ABO, Diego, Duffy, Kell, Kidd, Lewis,
      Lutheran, MNSs, P, Rhesus and Secretor), and Hp serum protein was carried out on
      a sample of 2,196 unrelated Costa Rican individuals of both sexes. Data was
      classified and analyzed according to geographic regions. Gene frequencies and the
      goodness of fit to Hardy-Weinberg equilibrium were estimated by the maximum
      likelihood method. A geographic structuring was observed in the Costa Rican
      population. All the regions of Costa Rica show higher heterozigosity values than
      the ones observed in the indigenous Costa Rican groups, but similar or slightly
      higher than the ones observed in the Spanish populations. The genetic distance
      analysis evidenced that the regions of Costa Rica group close to each other in
      intermediate positions between the Amerindians and the Spanish, fact that is
      coherent with the statement that attributes a intermediate origin to the general
      population of Costa Rica. The data contradicts the idea that the Central region
      has a radically different population than the rest of the country. The outcome of
      these markers revealed poor values of exclusion probability in forensic and
      paternity cases, which confirms the importance of their replacement for DNA
      markers in the outlines of human identification of judicial investigation
      systems. These results are similar to other studies made in Latin American
      populations.

PMID- 12189808
TI  - Nicaraguan population data on LDLR, GYPA, D7S8, HBGG, GC and HLA-DQA1 loci.
AB  - Nicaraguans have become the most numerous and fastest increasing minority in
      Costa Rica: at present they represent around 6% of the total population of the
      country. We have analyzed the allele and genotype frequencies of six PCR-based
      genetic markers (LDLR, GYPA, HBGG, D7S8, GC, and HLA-DQA1) in 100 unrelated
      Nicaraguans living in Costa Rica. All loci studied were in Hardy-Weinberg
      equilibrium. Some statistical parameters of forensic interest were also
      calculated (h, PD and CE). Allele frequencies of the markers HLA-DQA1 and GYPA
      were found to be significantly different between the populations of Nicaragua and
      Costa Rica. Nevertheless, genetic distances showed that Nicaragua is close to
      other Hispanic-admixed populations like those from Argentina, Chile, Colombia,
      Costa Rica, and USA Hispanics. The loci set was assessed to be useful for
      paternity testing and individual identification in the Nicaraguan population
      residing in Costa Rica.

PMID- 12189809
TI  - Presence of the orchid Oncidium maduroi (Orchidaceae: Oncidiinae) in Costa Rica.

PMID- 12189810
TI  - A Pleistocene mangrove cockle Anadara grandis (Pelecypoda: Arcidae) from
      Cartagena, Colombian Caribbean.

PMID- 12189811
TI  - [Flight of nocturnal butterflies in front of the coast of Chile (Lepidoptera:
      Sphingidae)].

PMID- 12189812
TI  - A spinal column malformation in the creolefish Paranthias colonus (Osteichthyes:
      Serranidae).

PMID- 12189813
TI  - [Taxonomy and distribution of the hermatypic corals (Scleractinia) of the
      Revillagigedo Archipelago, Mexico].
AB  - In spite of some recent detailed accounts about the scleractinian corals of the
      Archipielago de Revillagigedo, taxonomic work on this fauna has been sparse.
      Consequently, solid taxonomic background is needed, especially to support further
      studies at community level. During five field trips (between 1990 and 1995)
      collections were made at different depths on three of the archipelago islands:
      Socorro, Clarion and San Benedicto. A total of 250 specimens were collected.
      Coral identifications were made using co-occurrence methods concomitant with
      their descriptions, diagnosis and illustrations from a number of publications,
      and with morphological analysis. Coral distributions were taken from literature.
      Twenty-two species of zooxanthellate scleractinian corals are described, with
      their local and world-wide geographic distribution, and each illustrated with
      macro and microphotographs. Keys to the genera and species of the archipelago are
      also included. Porites and Pocillopora exhibit the highest species richness with
      a great intraspecific variation, as well as a number of morphological
      convergences within and between species which form species complexes, and several
      new species and morphs. Clarion, the oldest and most isolated island of the
      archipelago, harbors a number of coral morphs that are probable new species. More
      than half of the species found at the Revillagigedos are distributed exclusively
      on oceanic islands of the eastern Pacific and close to one third exist only at
      this archipelago. The Revillagigedos have strong faunal similarities and share a
      number of endemics with Clipperton Atoll, all of which support the idea that
      these islands constitute a separate biogeographic subregion within the eastern
      Pacific. Lastly, the present document substantiates the hypothesis that the
      Revillagigedos are important stepping-stone islands for the migration of in-shore
      marine species from the Central to the eastern Pacific.

PMID- 12189814
TI  - Environmental variables and intertidal beach annelids of Sao Sebastiao Channel
      (State of Sao Paulo, Brazil).
AB  - Benthic annelid communities were studied during a one-year period (August/95 to
      July/96) in two sectors of the beaches Engenho d'Agua and Sao Francisco, Sao
      Sebastiao Channel (Sao Paulo, Brazil), where the substrate is composed by a
      mixture of sand and rock fragments. Abiotic parameters such as salinity of
      interstitial water and sediment properties were used to characterize the
      environment. The polychaetes were well represented in the two sectors and their
      distribution was related with sediment type. The density of individuals and the
      number of taxa was higher at Sao Francisco, while the diversity and the evenness
      were higher at Engenho d'Agua. This difference can be a consequence of organic
      enrichment caused by domestic input, and of the lower and more variable salinity
      at Sao Francisco. Due to these factors, the high density of opportunistic
      species, like Capitella capitata ssp., Scolelepis squamata, Laeonereis acuta and
      several oligochaetes, represented 75.5% of total abundance at this sector.

PMID- 12189815
TI  - Gastropods and bivalves of commercial interest from the continental shelf of
      Jalisco and Colima, Mexico.
AB  - The distribution and abundance with respect to depth and type of substratum of 20
      species of gastropods and four species of bivalves of economic importance were
      examined in the continental shelf of Jalisco and Colima, Mexico. These species
      were taken with net trawls at depths from 24 to 83 m in August, 1988. Most
      individuals and species of gastropods were collected in stations with sandy silt
      substratum. Bivalves were collected in sandy silt and medium sand substrata. The
      six most abundant species represented 81.2% of all gastropods and bivalves
      collected. These species are: Cantharus pallidus, Fusinus dupetittouarsi, Ficus
      ventricosa, Hexaplex brassica, Harpa conoidalis and Arca pacifica.

PMID- 12189816
TI  - Occurrence and distribution of fresh-water molluscs in the Riacho Fundo Creek
      Basin, Brasilia, Brazil.
AB  - To study the distribution of molluscs in the Riacho Fundo Creek (cerrado region
      of central Brazil), five creek sites were sampled once every two months for one
      year. Molluscs were sampled using standardized kick-net sampling. Four species of
      molluscs were found: Physella cubensis, Melanoides tuberculata, Biomphalaria
      straminea and Pisidium sp. The most abundant were P. cubensis and Pisidium sp.
      Physella cubensis was most abundant in the dry season and Pisidium sp. was most
      abundant in the rainy season, probably reflecting the rainy season increase of
      water currents.

PMID- 12189817
TI  - [Morphometry of Sanguinolaria cruenta (Bivalvia: Psammobidae) in Tucacas Beach,
      Falcon, Venezuela)].
AB  - Three hundred and twelve shells of Sanguinolaria cruenta were collected in May
      1999 in a sandy beach in Tucacas, Falcon, Venezuela. For each shell, antero
      posterior length (Lap), overall height (Al), wide (An), weight (Pe), valves area
      (Arv), anterior length (La) and dorsal height (Ad) were measured. The descriptive
      statistic of the studied individuals, allows to appreciate that the variables
      that are good as parameters for the taxonomic description of S. cruenta are: Lap,
      Al, An, La y Ad, given their little variability. The maximum class frequencies is
      41-70 mm for Lap (91% of the population). Analysis of data determined
      relationships of Lap to An, Lap to La were isometric (Lap = 0.98078 An + 1.50456
      and Lap = 0.98052 La + 5.25840, respectively), whereas the other relationships
      indicate allometric growth.

PMID- 12189818
TI  - [Growth and sex maturation of a population of Saccostrea palmula (Mollusca:
      Bivalvia), Costa Rica].
AB  - Growth and sexual maturity in Saccostrea palmula were studied between May 1998
      and May 1999, in Morales estuary, Punta Morales, Puntarenas, Costa Rica (n = 540
      individuals according to sample size equation). The weight-length relationship
      for the population was Pt = 2.13 x 10(-2) Lt1.6602 and von Bertalanffy growth
      function was Lt = 68.2 (l- e -0.1577 t). The mean sex ratio was 1.00 male: 0.92
      females with sexually mature individuals found throughout the year. Spawning
      activity was highest between November and January. The mean condition index (IC =
      PCF/PV x 100) for the population was 121.53 +/- 2.24 and the mean meat yield was
      10.32 +/- 1.64%.

PMID- 12189819
TI  - [Abundance and body size of Menippe mercenaria (Crustacea: Brachyura), in
      artificial refuges in Quintana Roo, Mexico].
AB  - In Florida and Cuba the stone crab Menippe mercenaria (Say, 1818) is under strong
      fishing-pressure; nevertheless in the Mexican Caribbean it is considered as sub
      utilized and poorly known resource. Artificial shelters ("condominios cubanos")
      were used to study relative abundance, age structure, claw length-carapace
      amplitude relation, and population in three seasons and four sectors at Bahia
      Ascension, Quintana Roo, Mexico. The abundance varied according to the sector and
      sampling season: population was higher in the south and during the north wind
      ("Nortes") season (January to March). The carapace amplitude was directly
      proportional to claw length (r2 = 0.83, 0.97 and 0.89; p < 0.05 in females, males
      and total, respectively). The results suggest that specimens with 37.5 and 67.5
      mm of carapace amplitude are the most limited regarding refuge availability in
      the Bay.

PMID- 12189820
TI  - [Body size and fecundity of Juxtafabia muliniarum (Brachyura: Pinnotheridae)
      associated with Saccostrea palmula (Bivalvia: Ostreidae), Costa Rica].
AB  - Size and fecundity observations of pea crab (Juxtafabia muliniarum) from the
      paleal cavity of the oyster Saccostrea palmula were made from May 1998 to May
      1999. Infestation frequency was 18.52% in a sample of 540 oysters. Of 136 pea
      crabs, 36% were couples, 60% were single females and 4% were single males. The
      mean caparace length of J. muliniarum was 5.6 +/- 0.74 mm (range 4.0 to 7.6 mm)
      for females and 2.71 +/- 0.60 mm (range 1.6 to 4.0 mm) for males. The mean weight
      was 0.180 +/- 0.084 g (range 0.06 to 0.4 g) for females and 0.011 +/- 0.003 g
      (range 0.01 to 0.02 g) for males. Ovigerous females (43.75% of all females) were
      found in all months. The caparace length-fecundity relationship was F = 3904.6 Ln
      (Lc)--4651.1. The caparace length-weight relationship was P = 6 x 10(-4)
      Lc3.2122. The mean sex-ratio was 1.0 male: 2.4 females. Saccostrea palmula
      infected only by females was the dominant group (60.78%). This mollusk is a new
      host record for the crab.

PMID- 12189821
TI  - Effect of different densities of live and dead Chlorella vulgaris on the
      population growth of rotifers Brachionus calyciflorus and Brachionus patulus
      (Rotifera).
AB  - In order to maintain rotifer populations during periods of low algal production,
      it is necessary to offer alternate diets, some of which include forms of
      preserved algae. The present work is based on the effect of live and dead
      Chlorella vulgaris on the population growth of Brachionus calyciflorus and
      Brachionus patulus. The experimental design consisted of three algal levels (0.5
      x 10(6), 1.5 x 10(6) and 4.5 x 10(6) cells ml-1) offered in three forms (living,
      frozen and heat-killed). The maximal population density values for B.
      calyciflorus ranged from 55 +/- 1 ind. ml-1 (at 0.5 x 10(6) cells ml-1) to 471 +/
      72 ind. ml-1 (at 4.5 x 10(6) cells ml-1) with live Chlorella, but was much lower
      (6 +/- 1 to 26 +/- 6 ind. ml-1) with frozen or heat-killed alga under comparable
      food levels. However, the maximum population density of B. patulus under live or
      or heat-killed Chlorella was similar at comparable algal levels but when offered
      frozen algae it was four times less. The highest mean peak population density was
      1,277 +/- 83 ind. ml-1 under 4.5 x 10(6) cells ml-1. The rate of population
      increase for B. calyciflorus varied from 0.50 to 0.79 using live Chlorella, but
      under comparable conditions, this range was lower (0.21 to 0.31) for B. patulus.
      Results have been discussed in light of possible application for aquaculture.

PMID- 12189822
TI  - [Oropharyngeal morphology and food habits of Micropogonias furnieri (Pisces:
      Sciaenidae) in the North coast of Estado Sucre, Venezuela].
AB  - Morphology of the mandibular and pharyngeal region, and the feeding habits of
      Micropogonias furnieri were examined in 256 male and female specimens, between
      28.7 and 54.3 cm total length, collected around Morro Puerto Santo, in northeast
      Sucre State, Venezuela (10 degrees 45'00" N-63 degrees 8'0" W), from May 1989 to
      April 1990. Micropogonias furnieri has a small ventral mouth; protrusible
      premaxillary and dentary; first branchial arches with 21 to 27 gill rakers,
      generally 24 to 25; and 7 to 11 pyloric caecae. The index of vacuity was low,
      with mean value of 7.00%. The mean intestinal index was 0.72, indicative of
      carnivorous species. Analysis of frequency of occurrence, indicates preference
      for crustaceans (45.70%), mainly crabs (34.90%), followed by polychaetes
      (28.00%), fishes (11.41%) and occasionally mollusks and echinoderms (4.0 and
      3.9%, respectively). The diet of this species did not vary with sex.

PMID- 12189823
TI  - [Ichthyofauna fisheries in Bahia de Navidad, Jalisco, Mexico, associated to the
      El Nino event 1997-1998].
AB  - The ichthyofauna fished in Bahia de Navidad, Jalisco, Mexico in the Central
      Pacific was surveyed during 1998. Six thousand nine hundred and fourty-four
      organisms of 130 species were caught which weighted 3,231 kg. Nearly 30% of the
      species belonged to Carangidae. Haemulidae and Sciaenidae. The most important
      species in number and biomass were Microlepidotus brevipinnins, Caranx caninus
      and C. caballus. Species number, abundance and biomass fluctuated during the
      year. The largest number of species was caught in June (61), the minimum in March
      (33). January had the maximum abundance (1,397 organisms), while the minimum was
      obtained during August (251). The maximum biomass values were from January (556.5
      kg), and the lowest from August (114.7 kg). Eighteen species accumulated 87% of
      the total abundance, while 20 species represented 86.3% of the biomass. There
      were large in differences species number, abundance and biomass nets of different
      mesh size.

PMID- 12189824
TI  - [Length, body weight and sex of the golden Coryphaena hippurus (Perciformes:
      Coryphaenidae), of the littoral of Sinaloa, Nayarit and Baja California Sur,
      Mexico].
AB  - Dolphin fish population data were recorded from landings in Sinaloa, Nayarit and
      Baja Califonia Sur, Mexico, in 1997. Of 3,211 organisms, only 2,812 produced
      complete biometric data. The maximal length and weight were 192 cm and 30 kg. The
      three sampling sites and the climatic periods also were associated with different
      size (P < 0.05). The covariate analysis of weight and length relationships
      indicated significative differences (P < 0.05) for total data and by sex.
      Condition factor was higher throughout the study period in Mazatlan, and the
      variation was higher, in the spring. The sexual ratio was in Mazatlan constant,
      while there were more males in Nayarit in the fall and the spring and in Los
      Cabos in the spring. There may be population differences, between the central
      mexican Pacific Coast and the Peninsula of Baja data.

PMID- 12189825
TI  - Reproductive activity and condition index of Holacanthus passer (Teleostei:
      Pomacanthidae) in the Gulf of California, Mexico.
AB  - Annual variation and relationship between the gonadosomatic index (IG) and the
      condition index (K) of Holacanthus passer were evaluated in 194 specimens from
      Cueva de Leon, Gulf of California (24 degrees 02' N, 110 degrees 24' W). There
      was a significant negative correlation between IG and K in both sexes: indices
      exhibit an opposite seasonal pattern. The reproductive activity of both sexes is
      inversely related with nutritional status. There was a significant difference in
      IG but not in K values between males and females. The condition index may be used
      to determine reproduction time of the species in other localities without
      sacrificing the organisms. This could be a valuable tool to develop monitoring
      programs for fisheries and culture of this species.

PMID- 12189826
TI  - [Spatial distribution of Cordyceps spp. (Ascomycotina: Clavicipitaceae) and its
      impact on the ants in forests of Amazonian Colombian foothill].
AB  - Entomopathogenic fungi of the genus Cordyceps were sampled in the foothills of
      the Colombian Amazon region (450-600 msnm altitude. January and May, 1998, i.e.
      dry and wet seasons, respectively). Healthy and Cordyceps-parasitized ants from a
      nearly pristine, a naturally disturbed and a human-disturbed forests were
      collected on 100 quadrants (1 m2) per forest. Litter, shrubs and trunks were
      explored as substrates, and samples were gathered in vertical strata from 50 cm
      to 2 m high. Azteca was the predominant ant genus in near pristine forest whereas
      Camponotus, Pheidole and Crematogaster were dominant in disturbed forests. In the
      naturally disturbed forest we found 759 individuals of Cordyceps unilateralis and
      69 of C. lloydii var. binata parasitizing Camponotus spp. (Formicidae:
      Formicinae), whereas C. kniphofioides var. ponerinarum and C. australis were
      found only in six cases infecting the ants Paraponera clavata and Pachycondila
      crassinoda (Formicidae: Ponerinae). In the human disturbed forest it were found
      34 individuals of C. unilateralis on Camponotus. In the near pristine forest we
      did not find parasitized ants. The Camponotus spp. ants parasitized by C.
      unilateralis and C. lloydii var. binata were found predominantly in the
      substratum foliage up to 1 m. It was concluded that the incidence of Cordyceps
      ant interactions is not influenced by the conservation status of the forest.
      Instead, relative humidity and presence/absence of host ants appear to be key
      factors. Also, the microspatial distribution of the interactions seems to follow
      a definite pattern. This work observations support the hypothesis on coevolution
      of dispersion mechanisms in Cordyceps and ant pheromonal codes.

PMID- 12189827
TI  - In vitro micropropagation of Lawsonia inermis (Lythraceae).
AB  - A successful protocol was developed for mass propagation of Lawsonia inermis
      Linn., an important medicinal plant. Multiple shoots were induced in apical and
      axillary meristems derived from mature explants of L. inermis on Murashige and
      Skoog (1962) medium supplemented with 0.25 mg/l 6-benzylaminopurine (BA), 0.25
      mg/l Kinetin (Kn), 0.5 mg/l ascorbic acid and 3% (w/v) sucrose. The rate of
      multiplication was higher when the cultures were incubated under continuous light
      rather than the 14 hr photoperiod. Rooting was readily achieved upon transferring
      the microshoots onto MS basal semi-solid medium supplemented with 0.25 mg/l
      indole-3-butyric acid (IBA) after ten days of culture. Micropropagated plantlets
      were acclimatized and successfully grown in soil.

PMID- 12189828
TI  - Onset of in vitro rhizogenesis response and peroxidase activity in Zingiber
      officinale (Zingiberaceae).
AB  - The induction of rooting in microshoots of Zingiber officinale cvs. Suprava,
      Turia local, Suruchi and V3S18 was achieved on half-strength basal Murashige and
      Skoog's medium supplemented with 0.5-1.0 mg/l either indole-3-acetic acid (IAA)
      or indole-3-butyric acid (IBA) and 2% (w/v) sucrose within 7-9 days of culture.
      Rooting was inhibited when the microshoots were cultured under higher
      concentration of auxins. The microshoots cultured on medium supplemented with NAA
      induced large number of thin root hairs with friable calluses within 6-7 days.
      Peroxidase activity was determined during root induction (0-day to the 10th day
      at every 2 day interval) from microshoots derived in vitro. The activity was
      minimum in the inductive phase (primary) and at the maximum level during the root
      initiative phase. These finding may be useful in monitoring the rooting behaviour
      in microshoots derived from different subculture and peroxidase activity as a
      marker for root initiation.

PMID- 12189829
TI  - Vegetative propagation of Cecropia obtusifolia (Cecropiaceae).
AB  - Cecropia is a relatively well-known and well-studied genus in the Neotropics.
      Methods for the successful propagation of C. obtusifolia Bertoloni, 1840 from
      cuttings and air layering are described, and the results of an experiment to test
      the effect of two auxins, naphthalene acetic acid (NAA) and indole butyric acid
      (IBA), on adventitious root production in cuttings are presented. In general, C.
      obtusifolia cuttings respond well to adventitious root production (58.3% of
      cuttings survived to root), but air layering was the better method (93% of
      cuttings survived to root). The concentration of auxins used resulted in an
      overall significantly lower quality of roots produced compared with cuttings
      without auxin treatment. Future experiments using Cecropia could benefit from the
      use of isogenic plants produced by vegetative propagation.

PMID- 12189830
TI  - Woody plant diversity and structure of shade-grown-coffee plantations in northern
      Chiapas, Mexico.
AB  - Shade-grown coffee is an agricultural system that contains some forest-like
      characteristics. However, structure and diversity are poorly known in shade
      coffee systems. In 61 coffee-growers' plots of Chiapas, Mexico, structural
      variables of shade vegetation and coffee yields were measured, recording species
      and their use. Coffee stands had five vegetation strata. Seventy seven woody
      species mostly used as wood were found (mean density 371.4 trees per hectare).
      Ninety percent were native species (40% of the local flora), the remaining were
      introduced species, mainly fruit trees/shrubs. Diametric distribution resembles
      that of a secondary forest. Principal Coordinates Analysis grouped plots in four
      classes by the presence of Inga, however the majority of plots are diverse. There
      was no difference in equitability among groups or coffee yields. Coffee yield was
      835 g clean coffee per shrub, or ca. 1,668 kg ha-1. There is a significant role
      of shade-grown coffee as diversity refuge for woody plants and presumably
      associated fauna as well as an opportunity for shade-coffee growers to
      participate in the new biodiversity-friendly-coffee market.

PMID- 12189831
TI  - [Phenological behavior of the tree Elaeagia uxpanapensis (Rubiaceae), in a
      premontane rain forest of Costa Rica].
AB  - Phenology of the tree Elaeagia uxpanapensis was studied from March 1994 to March
      1998. This species is a canopy emergent in the A.M. Brenes Biological Reserve,
      Alajuela, Costa Rica. Fifteen mature trees were marked in order of appearance and
      observed every month using bionculars. A platform was built on one three better
      distinguished the transition from flowering to fruiting. Leaf abscission and
      budding were continuous throughout the year with several peaks, while flowering
      and fruit production occurred every 28 and 25 months, respectively. Leaf-fall was
      positively correlated with a ir temperature (n = 13, r = 0.44, p < 0.05), and
      fruiting with precipitation (n = 13, r = 0.37, p < 0.05) and relative humidity (n
      = 13, r = 0.44, p < 0.05). Bud formation was in inversely associated with
      precipitation (n = 13, r = 0.66 p < 0.05) and relative humidity ( n = 13, r =
      0.61, p < 0.05).

PMID- 12189832
TI  - [Nymphal feeding of Leptophlebiidae (Insecta: Ephemeroptera) in the Cano Paso del
      Diablo, Venezuela].
AB  - The food habits of aquatic nymphs of 12 species of the family Leptophlebiidae
      were determined in a tropical intermittent stream in Venezuela. Three monthly
      samples of aquatic insects were taken from January to June in 1989. Two hundred
      and twenty-five stomach contents were analyzed. The results obtained were
      compared by the functional feeding groups classification. Species of the
      Thraulodes and Farrodes genera show significant differences in their diets.

PMID- 12189834
TI  - Interlocking of molecular rhombi into a 2D polyrotaxane network via pi-pi
      interactions. Crystal structure of [Cu2(bpa)2(phen)2(H2O)]2.2H2O (bpa2- =
      biphenyl-4,4'-dicarboxylate, phen = 1,10-phenanthroline).
AB  - In the solid state, interlocking of the lateral phen ligands at the acute angle
      sites of the molecular [Cu2(bpa)2-(phen)2(H2O)]2 rhombi via aromatic pi-pi
      stacking interactions into the cavities of the adjacent rhombi generates
      laminated polyrotaxanes that are further assembled into a 3D network via similar
      interactions between the phen ligands at the obtuse angle sites.

PMID- 12189833
TI  - Optical barcoding of colloidal suspensions: applications in genomics, proteomics
      and drug discovery.
AB  - The enormous amount of information generated through sequencing of the human
      genome has increased demands for more economical and flexible alternatives in
      genomics, proteomics and drug discovery. Many companies and institutions have
      recognised the potential of increasing the size and complexity of chemical
      libraries by producing large chemical libraries on colloidal support beads. Since
      colloid-based compounds in a suspension are randomly located, an encoding system
      such as optical barcoding is required to permit rapid elucidation of the compound
      structures. We describe in this article innovative methods for optical barcoding
      of colloids for use as support beads in both combinatorial and non-combinatorial
      libraries. We focus in particular on the difficult problem of barcoding extremely
      large libraries, which if solved, will transform the manner in which genomics,
      proteomics and drug discovery research is currently performed.

PMID- 12189835
TI  - Selective hydrolysis of peptides promoted by metal ions: a positional scanning
      approach.
AB  - Rapid, microplate-based fluorogenic screening of a positional scanning
      combinatorial library accurately predicts the sequence specificity of metal
      assisted peptide hydrolysis.

PMID- 12189836
TI  - Inter-digitation approach to encapsulation of C60: [C60 [symbol: see text] (p
      phenylcalix[5]arene)2].
AB  - p-Phenylcalix[5]arene shows a strong and selective binding of C60 in toluene
      resulting in crystallisation of a hemispherically inter-digitated 2:1 complex;
      the receptor itself crystallizes from toluene with self assembly through phenyl
      group inclusion.

PMID- 12189837
TI  - A new nido-5-vertex cluster, phosphacarba-nido-pentaborane, 2-tBu-1,2-PCB3H5.
AB  - The gas-phase reaction of the phosphaalkyne P identical to CtBu with
      tetraborane(10), B4H10, yields the nido five-vertex phosphacarbaborane cluster
      compound 2-tBu-1,2-PCB3H5 2 with an unusual 31P NMR peak shift of -500.5 ppm.

PMID- 12189838
TI  - Reversible covalent chemistry of CO2.
AB  - Reversible reaction of CO2 with fluorescently active amines in polar aprotic
      solvent rapidly results in carbamic acids, which significantly enhances the
      solution fluorescence.

PMID- 12189840
TI  - Asymmetric synthesis of alpha-amino acids: indium-mediated reactions of glyoxylic
      oxime ether in aqueous media.
AB  - The indium-mediated allylation and alkylation reactions of the Oppolzer
      camphorsultam derivative of glyoxylic oxime ether proceeded with excellent
      diastereoselectivity in aqueous media, providing a variety of enantiomerically
      pure alpha-amino acids.

PMID- 12189839
TI  - Enzyme-catalysed oxygenation and deoxygenation routes to chiral thiosulfinates.
AB  - Enantioenriched thiosulfinates have been obtained by dioxygenase- and
      chloroperoxidase-catalysed oxidation of 1,2-disulfides and dimethyl sulfoxide
      reductase-catalysed deoxygenation.

PMID- 12189841
TI  - A general, norbornyl based approach to anti-Bredt alkenes via sequential RCM
      fragmentation strategy.
AB  - A general protocol for the synthesis of bicyclo[n.3.1]frameworks with bridgehead
      double bond (anti-Bredt alkenes), from a common, readily available norbornyl
      precursor, involving sequential ring closure metathesis (RCM) and Wharton
      fragmentation is outlined.

PMID- 12189842
TI  - Probing the effect of a 3'-S-phosphorothiolate link on the conformation of a
      DNA:RNA hybrid; implications for antisense drug design.
AB  - The effects of a single 3'-S-phosphorothiolate link in the DNA strand of a
      DNA:RNA dodecamer duplex is described; the sulfur induces a conformational shift
      in the (attached) sugar pucker, as shown by 1H NMR studies, and increases the
      thermal stability of the duplex compared to the non-modified system.

PMID- 12189843
TI  - Tuning the optical properties of Prussian blue-like complexes.
AB  - The rational design of the organic ligand allows to finely tune the degree of
      delocalization of mixed-valence Prussian blue-like molecules.

PMID- 12189844
TI  - Preparation of titania particles utilizing the insoluble phase interface in a
      microchannel reactor.
AB  - A stable interface between two insoluble currents in a microchannel reactor has
      been obtained by selecting the solvents and adjusting the flow rate; titania
      particles with a size of less than 10 nm could be prepared continuously on this
      interface; this new method shows great advantage for the control and measurement
      of particle sizes.

PMID- 12189846
TI  - Synthesis, characterization and catalytic properties of trivalent iron
      substituted hexagonal mesoporous aluminophosphates.
AB  - Trivalent iron substituted hexagonal mesoporous aluminophosphate molecular sieve
      has been synthesized and characterized for the first time, which showed excellent
      catalytic activity and reusability for the cyclohexane oxidation reaction under
      mild conditions.

PMID- 12189845
TI  - Slow charge recombination in dye-sensitised solar cells (DSSC) using Al2O3 coated
      nanoporous TiO2 films.
AB  - The conformal growth of an overlayer of Al2O3 on a nanocrystalline TiO2 film is
      shown to result in a 4-fold retardation of interfacial charge recombination, and
      a 30% improvement in photovoltaic device efficiency.

PMID- 12189847
TI  - High selectivity of oxidative dehydrogenation of ethane to ethylene in an oxygen
      permeable membrane reactor.
AB  - An oxygen permeable membrane based on Ba0.5Sr0.5Co0.8Fe0.2O3-delta is used to
      supply lattice oxide continuously for oxidative dehydrogenation of ethane to
      ethylene with selectivity as high as 90% at 650 degrees C.

PMID- 12189848
TI  - 13C kinetic isotope effects in the copper(I)-mediated living radical
      polymerization of methyl methacrylate.
AB  - Carbon-13 kinetic isotope effects (KIEs) have been determined for free-radical
      and copper-mediated living radical polymerizations of methyl methacrylate at 60
      degrees C. While free-radical polymerization shows only one primary 13C KIE, on
      the least-substituted double bond carbon (k12/k13 = 1.045), two significant KIEs
      are observed, one on each double bond carbon, for copper-mediated polymerization
      (k12/k13(H2C=) = 1.050, k12/k13(=C <) = 1.010), showing that copper-mediated
      living radical polymerization does not propagate via a simple free radical
      process.

PMID- 12189849
TI  - New domino transposition/intramolecular Diels-Alder reaction in monocyclic
      allenols: a general strategy for tricyclic compounds.
AB  - A novel and direct synthetic strategy to prepare fused tricycles has been
      developed from monocyclic allenols, masked functionalized dienes, which underwent
      a domino allenol transposition/intramolecular Diels-Alder reaction.

PMID- 12189850
TI  - Benzenthiolate bridged binuclear group 12 metal complexes with TTF fused
      dithiolate ligand, a new synthetic approach using cluster-cracking reaction.
AB  - Novel binuclear dithiolate complexes (Me4N)2[M2-(SPh)2(S2TTF(SMe)2)2] (M = Cd and
      Zn) have been synthesized by a new cluster-cracking method.

PMID- 12189851
TI  - Architectural formation of a conjugated bimetallic Pd(II) complex via oxidative
      complexation and a tetracyclic Pd(II) complex via self-assembling complexation.
AB  - The conjugated homobimetallic palladium(II) complex [(L1)Pd(qd)Pd(L1)] (qd =
      quinonediimine) was obtained in a one-pot reaction by the in-situ oxidative
      complexation of 1,4-phenylenediamine with the palladium(II) complex
      [(L1)Pd(MeCN)] (H2L1 = N,N'-bis(2-phenylethyl)-2,6-pyridinedicarboxamide) while
      in the absence of an additional ligand [(L1)Pd(MeCN)] was converted to the amide
      bridged macrocyclic tetramer [Pd(L1)]4.

PMID- 12189852
TI  - First tetrameric NiII cluster with planar triangular topology exhibiting
      ferromagnetic pathways.
AB  - [Ni4L3(H2O)2](ClO4)2.2H2O 1, the first tetranuclear NiII cluster showing triangle
      planar geometry, formed with a new carboxylic-functionalized 1,5-diazacyclooctane
      bridging ligand has been presented; the global magnetic coupling is ferromagnetic
      and anisotropic calculations have been made.

PMID- 12189853
TI  - Fabrication of macroporous SiC from templated preceramic polymers.
AB  - Macroporous SiC with a highly ordered pore array was prepared for the first time
      using low molecular weight SiC preceramic polymers such as polymethylsilane or
      polycarbosilane by utilizing sacrificial colloidal silica crystalline arrays, as
      a template which were subsequently etched off after pyrolysis in an argon
      atmosphere.

PMID- 12189854
TI  - Highly impermeable vesicles composed of conformationally restricted
      phosphatidylethanolamine.
AB  - Vesicles composed of a phosphatidylethanolamine derivative with a cyclopropyl
      containing interfacial region are twenty-seven times less permeable than vesicles
      composed of a closely related analogue.

PMID- 12189855
TI  - Electronic structure of light-induced lophyl radical derived from a novel
      hexaarylbiimidazole with pi-conjugated chromophore.
AB  - A novel photochromic hexaarylbiimidazole with a bithienyl group as an extended pi
      conjugation unit was synthesized and the light-induced lophyl radical was found
      to be stabilized due to the delocalization of an unpaired electron, and to
      strongly absorb near-infrared light.

PMID- 12189856
TI  - Fabrication of Co3O4 nanorods by calcination of precursor powders prepared in a
      novel inverse microemulsion.
AB  - Co3O4 nanorods were prepared by improving traditional molten salt synthesis; the
      length and diameters of the Co3O4 nanorods were about 10 microns and 40-100 nm,
      respectively; the mechanism of formation of the Co3O4 nanorods is discussed.

PMID- 12189857
TI  - An unprecedented 1D ladder coordination polymer based on a pentanuclear
      copper(II) 2,4,6-tris(dipyridin-2-ylamino)-1,3,5-triazine building block.
AB  - Copper(II) nitrate reacts with the rigid polydentate triple-connecting dpyatriz
      ligand in acetonitrile to an unprecedented infinite molecular ladder in which
      five-coordinated copper pseudo-dimer are bridged by nitrate anions and the
      coordination polymer chains are linked by hexacoordinated copper ions leading to
      the formation of large guest cavities.

PMID- 12189858
TI  - New phases of sp2-bonded boron nitride: the 12R and 24R polytypes.
AB  - sp2-Bonded polytypes of graphite-like boron nitride are evidenced in the
      approximately twin-related bicrystal-like BN nanofibres synthesized by a high
      temperature substitution reaction between carbon nanofibres and boron oxides in
      N2 atmosphere; the material shows a main 12R phase of A'ABC/C'CAB/B'BCA packing
      and a minor 24R phase with an A'ABC/BB'C'A'/C'CAB/ ... packing sequence.

PMID- 12189859
TI  - [V(III)(H2O)]3O(O2CC6H4CO2)3.(Cl, 9H2O) (MIL-59): a rare example of
      vanadocarboxylate with a magnetically frustrated three-dimensional hybrid
      framework.
AB  - [V(III)(H2O)]3O(O2CC6H4CO2)3.(Cl, 9H2O) (denoted MIL-59) presents a three
      dimensional framework built up from octahedral vanadium trimers joined via the
      isophthalate anionic linkers to delimit cages where water molecules and chlorine
      anions are occluded; the frustrated magnetic behaviour of MIL-59 is discussed.

PMID- 12189860
TI  - ZrCl4-promoted halogen migration during an electrophilic amination of halogenated
      phenols.
AB  - An electrophilic amination of halogenated phenols with diisopropyl
      diazenedicarboxylate in the presence of ZrCl4 as a Lewis acid, accompanied by a
      halogen migration, was demonstrated for the first time; the fluorine, chlorine,
      bromine, or iodine atom migrated during the amination process under mild reaction
      conditions.

PMID- 12189861
TI  - Synthesis of mono-substituted 2,2'-bipyridines.
AB  - The rapid synthesis of 4-aryl-2,2'-bipyridines is described leading to some
      previously reported compounds in good yields in addition to some new
      functionalized bipyridines.

PMID- 12189862
TI  - Nucleophilic attack at pyridine nitrogen and its use to access a novel mono
      anionic ligand for iron-based ethylene polymerisation catalysts.
AB  - Addition of MeLi to bis(imino)pyridines results in an unprecedented nucleophilic
      attack at pyridine nitrogen to afford novel mono-anionic [N,N,N] ligands: their
      treatment with FeCl3, followed by MAO activation, affords highly active ethylene
      polymerisation catalysts.

PMID- 12189863
TI  - Surface-enhanced IR absorption on platinum nanoparticles: an application to real
      time monitoring of electrocatalytic reactions.
AB  - Molecules adsorbed on Pt nanoparticles prepared on Si by a chemical deposition
      technique exhibit extremely strong IR absorption, which enables fast time
      resolved IR monitoring of electrocatalytic reactions.

PMID- 12189864
TI  - Co-adsorption of surfactants and water at inorganic solid surfaces.
AB  - Computer simulations of the co-adsorption of water and methanoic acid at a range
      of surface features of calcite and fluorite minerals have shown that the relative
      adsorption energies for the two minerals are reversed when solvent effects are
      included in the calculations, a finding which is important in the search for
      effective surfactant reagents in flotation techniques, which are used extensively
      in the mining and pharmaceutical industries and in environmental remediation
      processes.

PMID- 12189866
TI  - Delamination of layered double hydroxides in polar monomers: new LDH-acrylate
      nanocomposites.
AB  - The layered double hydroxide Mg2Al(OH)6(C12H25SO4) was delaminated to give high
      levels of inclusion in acrylate monomers; subsequent polymerisation of the
      monomers containing the LDH dispersion gave polyacrylates with the inorganic
      component still in the delaminated form.

PMID- 12189865
TI  - Solution and solid-phase chemoselective synthesis of (1-6)-amino(methoxy) di- and
      trisaccharide analogues.
AB  - Disaccharide and trisaccharide mimics containing the amino(methoxy)
      interglycosidic linkage were obtained by chemoselective condensation of
      unprotected aldoses in an aqueous environment both in solution and in solid
      phase.

PMID- 12189868
TI  - Surface modification via 'lock and key' specific self-assembly of polyhedral
      oligomeric silsequioxane (POSS) derivatives to modified gold surfaces.
AB  - Diaminopyridine (DAP) functionalized POSS derivatives self-assemble on thymine
      functionalized monolayers on gold surfaces affording hybrid inorganic/organic
      surfaces.

PMID- 12189867
TI  - A highly water-soluble 2:1 beta-cyclodextrin-fullerene conjugate.
AB  - A novel 2:1 (permethylated-beta-cyclodextrin)-fullerene conjugate has been
      synthesised; highly soluble in cold water with formation of aggregates, it
      displays a negative solubility coefficient and has a partition coefficient
      between octanol and water (Log P = 1.58) in the suitable range for biological
      studies.

PMID- 12189869
TI  - Structural and morphological characterization of synthetic chrysotile single
      crystals.
AB  - Stoichiometric chrysotile single crystals have been synthesized as a unique phase
      by hydrothermal reaction under controlled conditions; the synthesized
      monocrystals show a cylinder-in-cylinder morphology and can be used as a
      reference sample with definite chemical composition to investigate the factors
      responsible of the chrysotile cytotoxicities and carcinogenicities.

PMID- 12189870
TI  - Synthesis of epoxides from aldehydes and tosylhydrazone salts catalysed by
      triphenylarsine: complete trans selectivity for all combinations of coupling
      partners.
AB  - Triphenylarsine catalyses the formation of epoxides from carbonyl compounds and
      tosylhydrazone salts. This convergent synthesis gives complete trans selectivity
      for all aldehyde and tosylhydrazone salt coupling partners.

PMID- 12189871
TI  - Dimeric iron n-confused porphyrin complexes.
AB  - A dimeric iron N-confused porphyrin, [Fe(NCTPP)]2 was obtained from the anaerobic
      reaction of Fe(NCTPP)Br with NaSePh while under aerobic conditions a hydroxo
      bridged iron dimer with Na bridging the outer-N atoms was obtained and
      oxygenation occurred on the inner core pyrrolic carbon to form a novel ONCTPP
      porphyrinic ring.

PMID- 12189872
TI  - Photoelectrochemical study of Zn cytochrome-c immobilised on a nanoporous metal
      oxide electrode.
AB  - Transient optical spectroscopies and photocurrent action spectra are used to
      demonstrate photoinduced charge separation between zinc-substituted cytochrome c
      and a nanocrystalline TiO2 electrode.

PMID- 12189873
TI  - The crystal structure of the 'pentamethylcyclopentadienyl cation' is that of the
      pentamethylcyclopentenyl cation.
AB  - The recently reported X-ray crystal structure of the [B(C6F5)4]- salt of the
      'pentamethylcyclopentadienyl cation' is actually that of pentamethylcyclopentenyl
      tetrakis(pentafluorophenyl)borate.

PMID- 12189874
TI  - First diastereoselective formation of lanthanide triple helical complexes with a
      terdentate chiral C2 symmetric ligand.
AB  - Steric interactions between three enantiopure terdentate ligands leads to the
      diastereoselective formation of luminescent triple helical lanthanide complexes.

PMID- 12189875
TI  - Highly enantioselective alkynylation of aldehydes catalyzed by a readily
      available chiral amino alcohol-based ligand.
AB  - A new inexpensive chiral amino alcohol-based ligand, (1S,2S)-2-N,N-dimethylamino
      1-(p-nitrophenyl)-3- (t-butyldimethylsilyloxy)propane-1-ol, was developed for the
      asymmetric alkynylation of aliphatic and aromatic aldehydes, to prepare the
      corresponding propargylic alcohols in high yields with up to 99% ee.

PMID- 12189876
TI  - TiO2-montmorillonite composites via supercritical intercalation.
AB  - The successful preparation of TiO2-montmorillonite mesoporous composites using
      intercalation of titanium isopropoxide dissolved in supercritical carbon dioxide
      involved ion exchange of interlayer cations by hydrophobic cations.

PMID- 12189877
TI  - Formation of TiO2 nanoparticles in water-in-CO2 microemulsions.
AB  - Titanium dioxide nanoparticles can be produced by the controlled hydrolysis of
      titanium tetraisopropoxide in water-in-CO2 (w/c) microemulsions stabilized with
      the surfactants ammonium carboxylate perfluoropolyether (PFPE-NH4) and
      poly(dimethyl amino ethyl methacrylate-block-1H,1H,2H,2H-perfluorooctyl
      methacrylate) (PDMAEMA-b-PFOMA); the greater control of hydrolysis and particle
      growth with PDMAEMA-b-PFOMA is consistent with the differences in the stabilities
      and interactions for these two microemulsions.

PMID- 12189878
TI  - Synthesis of novel 1,3-bis(5-diarylaminothiophen-2-yl)isothianaphthenes.
AB  - We report the synthesis, electrochemical and optical properties of novel 1,3
      bis(5-diarylaminothiophen-2-yl)isothianaphthenes obtained by palladium-catalysed
      amination of 1,3-bis(5-bromothiophen-2-yl)isothianaphthene with diarylamines.

PMID- 12189879
TI  - A convergent, flexible synthesis of 1,3-dienes.
AB  - 1,3-Dienes were prepared from 1,4-ketoxanthates, obtained by the radical addition
      reaction of an S-(2-oxoalkyl) xanthate to a terminal olefin, through the DBU
      induced thermal elimination of sulfur dioxide from the derived 2-sulfolenes.

PMID- 12189880
TI  - Photosensitized production of doubly reduced methylviologen followed by highly
      efficient methylviologen radical formation using self-assembling ruthenium(II)
      complexes.
AB  - Supramolecular fibers of Ru(II) complexes act as efficient photosensitizers,
      photochemically generating methylviologen radical (MV.+) and then converting it
      quantitatively to doubly reduced methylviologen, (MV0), in the presence of
      triethanolamine.

PMID- 12189881
TI  - A direct template synthesis of nanoporous carbons with high mechanical stability
      using as-synthesized MCM-48 hosts.
AB  - A simple and efficient synthetic method for highly ordered nanoporous carbons
      with high mechanical and thermal stability has been performed through a direct
      template carbonization using as-synthesized MCM-48 hosts.

PMID- 12189882
TI  - Ionic liquids based on N-vinyl-gamma-butyrolactam: potential liquid electrolytes
      and green solvents.
AB  - The first examples of room temperature ionic liquids, containing N-alkyl-N-vinyl
      2-pyrrolidinonium (N-alkyl-N-vinyl-gamma-butyrolactam) cations in combination
      with bromide and tetrafluoroborate anions, have been synthesized and the
      spectroscopic and physical characteristics of this family of ionic liquids have
      been investigated for intended use as liquid electrolytes and green solvents.

PMID- 12189883
TI  - Novel tris(2,2'-bipyridine)ruthenium(II) cathodic electrochemiluminescence in
      aqueous solution at a glassy carbon electrode.
AB  - A novel approach of generating cathodic electrochemiluminescence of Ru(bpy)3(2+)
      at -0.4 V triggered by reactive oxygen species is reported for detecting
      alkylamines and some organic acids.

PMID- 12189884
TI  - A new approach to functionalized spiropiperidines through tandem RCM and nitrogen
      directed reactions.
AB  - The synthesis of a functionalized spiropiperidine via a tandem ring closing
      metathesis strategy is described, furthermore, the regio- and stereoselective
      functionalization of this compound has been achieved through a novel nitrogen
      directed epoxidation reaction.

PMID- 12189885
TI  - Ion-induced discrete charging of immobilized water-soluble gold nanoclusters.
AB  - Hydrophilic gold nanoclusters were immobilized onto monolayer-modified gold
      electrodes and PF6-(-)induced rectification and stepwise capacitance charging was
      studied in aqueous supporting electrolyte by cyclic voltammetry and ac
      voltammetry.

PMID- 12189886
TI  - Tandem cobalt mediated rearrangement and Pauson-Khand reaction for the synthesis
      of functionalized polycyclic systems.
AB  - The cobalt mediated rearrangement of enol ether complex 2 furnishes cyclic ketone
      6, which undergoes an intramolecular Pauson-Khand reaction allowing access to
      functionalized polycyclic systems.

PMID- 12189887
TI  - Preparation of alpha, beta-acetylenic ketones by catalytic heterogeneous
      oxidation of alkynes.
AB  - Covalent grafting of iron phthalocyanines onto silica affords active catalysts
      for selective oxidation of alkynes and propargylic alcohols to alpha, beta
      acetylenic ketones, highly valuable precursors in the preparation of fine
      chemicals.

PMID- 12189888
TI  - Synthesis of cyclophanetetrayne complexes from bis(propargyldicobalt) dication
      equivalents.
AB  - Nicholas reactions of the p-phenyl linked bis(propargyl acetate) complex (3a)
      with electron rich arenes give cyclophanetetrayne complexes (5). The use of
      bis(propargyl ether) complex (8) with (3a) allows formation of a mixed
      cyclophanetetrayne complex (9), and in addition gives retro
      Nicholas/intramolecular Nicholas reaction product (2).

PMID- 12189889
TI  - Utility of calculated 13C NMR chemical shifts in differentiating conformational
      isomers: a study of metal-complexed and uncomplexed bispidines.
AB  - Calculated 13C NMR chemical shifts were key to assigning the structures of the
      conformational forms of complexed and uncomplexed bispidine derivatives.

PMID- 12189890
TI  - Benign neglect in home healthcare leads to death.

PMID- 12189891
TI  - CRNA leaves catheter in pt.: doctor liable under 'ostensible agency'. Case on
      point: Parker v. Freilich, 2002 WL 1308708 A.2d.-PA.

PMID- 12189892
TI  - LA: RN with preexisting condition seeks W.C.: is aggravation of preexisting
      injury compensible?

PMID- 12189893
TI  - SC: nurse releases restraints--pt. fractures hip: state hospital immune unless
      "gross negligence".

PMID- 12189894
TI  - Failure to account for 'lost' or 'missing' controlled substance. Case on point:
      Matthias v. Iowa Board of Nursing, 2002 WL 1429951 N.W.2d-IA.

PMID- 12189895
TI  - Physicians' attitudes and advice concerning pregnancy subsequent to the birth of
      a stillborn child.
AB  - The aim of this study was to identify physicians' approaches to pregnancy
      subsequent to the birth of a stillborn child. In a 48-question, cross-sectional
      survey performed in 1997 one specific question dealt with advice given to the
      women/parents about possible subsequent pregnancy. The present study analyzes the
      responses to that open-ended question. Fifty-eight out of 61 Swedish hospitals
      with departments of obstetrics and gynecology participated in the study. Of 594
      physicians, 552 answered the open-ended question (93%) with 802 items of advice.
      The most frequent approach to subsequent pregnancy, expressed by a majority of
      physicians, was their own support to the couples (59%). Regarding gender
      differences the females were more likely to mention support strategies than their
      colleagues (p = 0.005). Significantly more female gynecologists than male (p =
      0.005) recommended care during the new pregnancy at a special antenatal clinic.
      The statement that 'advice depends on diagnosis' was made by 27%, while 22%
      advocated that parents first work through the grief of the stillbirth (mentioned
      significantly more often by females, p = 0.014). A minority of physicians mention
      giving specific advice about the timing of next pregnancy. The study highlights
      physicians' concerns to support parents through a subsequent pregnancy whilst
      demonstrating that considerable variation exists in their advice, or lack of it,
      with regard to timing of another pregnancy.

PMID- 12189896
TI  - Obstetric difficulties in developing countries motivate preference for birth
      size.
AB  - The aim of this study was to assess the influence of labor difficulties on
      mothers preference for birth size. A total of 502 pregnant Ghanaian women were
      interviewed to ascertain what size of infant they wished to deliver. Information
      on reasons, measures taken to achieve preferred birth size and birth weight of
      infants delivered by them was obtained. Results showed that even though mothers
      had particular preferences for birth size, actual birth weight of infants
      delivered did not tally with mothers' preference. More women with previous
      childbirth experience wanted small infants than those who had no experience.
      Overall 41% of the mothers preferred small or medium size infants for easy labor.
      Large infants on delivery were preferred by 11% of the mothers because they
      claimed large infants are tough. Approximately 48% of mothers had no particular
      preference for birth size. It seemed mothers wanting small infants had previous
      labor problems due to large birth size. A substantial number (40%) of the mothers
      did not take measures to achieve the preferred birth size. About 4% reported to
      have reduced their dietary intake to less than the non-pregnancy intake to
      deliver small infants. About 7% of the women who preferred large infants at birth
      claimed they ate more food to achieve their aim. Mothers who had mechanical
      difficulties during labor delivered infants of significantly higher birth weight
      than those who delivered normally without extra assistance (p < 0.002). Women who
      experienced a difficult childbirth, believed that high infant birth weight can
      pose labor problems.

PMID- 12189897
TI  - Sexual outcomes following treatment for early-stage gynecological cancer: a
      prospective and cross-sectional multi-center study.
AB  - This study evaluates the impact of early-stage gynecological cancer and its
      treatment on sexuality and assessed needs for care regarding sexual
      rehabilitation. Data from 58 women from a prospective, longitudinal study were
      compared to data from 220 women from a cross-sectional study. Patients in the
      prospective study completed questionnaires prior to treatment and then 6 and 12
      months post-treatment. A single assessment was obtained from patients in the
      cross-sectional study. All women had a partner. Both groups were comparable on
      important independent variables. Both samples had an equal level of sexual
      contact, but participants in the cross-sectional study (mean time 46 months post
      treatment) reported a higher frequency of sexual problems, were more troubled by
      those problems and reported a lower sexual satisfaction. However, in both groups
      the level of the reported dysfunctions was relatively low. Around 80% of the
      patients were satisfied with the information provided on sexual rehabilitation.
      Little need for extra care on sexual rehabilitation was reported. In conclusion,
      women with early-stage gynecological cancer were not especially prone to severe
      sexual problems and seemed to cope well with the consequences of cancer and its
      treatment on their sexual lives. It was suggested that this relatively positive
      outcome is a result of the improved patient care and education on sexual aspects
      in the last decade.

PMID- 12189898
TI  - Personality, social support, coping and emotional distress after repeated
      spontaneous abortions.
AB  - Systematic investigations on the emotional impacts of repeated spontaneous
      abortions have been few. We mounted a prospective study of a cohort of couples
      who had experienced two consecutive first trimester spontaneous abortions and for
      whom no clearly identifiable causes were found. The present report is based on
      the first part of the study and examines: (1) emotional distress reported by the
      miscarrying women at six months (median, range 1-12 months) after two abortions;
      and (2) psychosocial predictors influencing such distress. The mean score of the
      women on the Symptom Checklist 90-Revised--one of the most popular self-report
      scales for psychopathology--was 0.38, whereas that for the general population is
      reported to be 0.26 (the higher the score, the more psychopathology). Fourteen
      percent of the cohort scored above the cutoff point for mental disorders
      screening. Factors examined and found non-influential upon the level of emotional
      distress include: the maternal age; whether the last pregnancy was planned and
      wished for or not; and coping styles of the women after the abortions. Control by
      the husbands over the marital relationship and neurotic personality traits of the
      women increased the emotional distress, whereas the social support the women
      perceive decreased it. These findings suggest that martial and social support are
      important in determining the level of psychiatric morbidity after repeated
      abortions.

PMID- 12189899
TI  - Euthanasia--or, death on request.

PMID- 12189900
TI  - A time to be born and a time to die: reflections on euthanasia.
AB  - Euthanasia is, and probably will remain a controversial issue. Although many
      doctors will agree that under certain circumstances a demand for euthanasia
      should be granted (and in fact often is granted when the occasion arises), the
      subject generally gives rise to very emotional debates. Attempts to decriminalize
      euthanasia generally fail, and this contrasts sharply with the attitude of many
      towards issues like capital punishment and the objectives of, for example, the
      military. In this essay this apparent contradiction is discussed from the
      evolutionary biological point of view. It is argued that euthanasia always
      concerns the death of a member of some 'in-group' (which in some way we regard as
      part of ourselves), while capital punishment and the death of (political) enemies
      always concerns the death of members of some 'out-group'. It is inherent in our
      genetic make-up, evolved over millions of years, that we oppose the death of
      members of in-groups and are indifferent to (even promote) the death of members
      of out-groups. Attempts to regulate these inclinations by cultural and religious
      wisdom or commands ('[there is] a time to be born and a time to die' and 'love
      thy enemies like thyself') are only marginally successful, because biological
      urges generally dominate cultural notions.

PMID- 12189901
TI  - Sex, gender and reproduction.

PMID- 12189903
TI  - Development of the Delivery Fear Scale.
AB  - This article reviews the development of the Delivery Fear Scale (DFS) to measure
      fear during labor and delivery. In an initial study, 92 women in labor answered a
      list of 60 items, expressing fear-related appraisals and their contrasts that
      were characteristic of women in labor. The items were then selected by means of
      an item-total analysis. In a second study, the final list of ten items was tested
      psychometrically, and a semi-structured interview was performed on 45 women in
      labor, to explore the women's descriptions of the content of each of the ten
      items. According to the content analysis of the interviews, the dominating
      connotation of the ten items is fear based on the appraisal of being captured.
      The studies show that the DFS is a questionnaire that almost effortlessly can be
      completed within 60-90 seconds during any moment of labor and delivery. The scale
      has a good reliability: Cronbach's alpha was 0.88 in both studies.

PMID- 12189902
TI  - Premenarcheal Mexican girls' expectations concerning perimenstrual changes and
      menstrual attitudes.
AB  - The objective of this study was to determine both the perimenstrual changes that
      Mexican premenarcheal girls expect to experience and their attitudes toward
      menstruation. A total of 750 premenarcheal girls in fifth and sixth grade were
      studied. Participants completed a Perimenstrual Change Checklist, which listed 20
      negative possible perimenstrual changes and ten positive ones, and a Spanish
      version of the Adolescent Menstrual Attitude Questionnaire. The results showed a
      set of mostly negative perimenstrual expectations, the most common being
      discomfort, cramps or abdominal pain and mood swings. Concerning menstrual
      attitudes, the girls scored highest on secrecy, followed by negative feelings and
      by positive feelings. The girls who perceived menstruation as a negative event
      and with secrecy, expected more negative perimenstrual changes, while those who
      perceived menstruation as a positive event expected more positive perimenstrual
      changes. We believe premenarcheal girls, with no personal experience, must be
      more influenced by cultural stereotypes which are of a negative nature.

PMID- 12189904
TI  - Variation in the fatty acid binding protein 2 gene is not associated with markers
      of metabolic syndrome in patients with coronary heart disease.
AB  - BACKGROUND AND AIM: It has been suggested that the threonine (Thr) 54 allele of
      the intestinal fatty acid binding protein 2 (FABP2) gene is associated with
      insulin resistance and affects the fatty acid composition of serum lipids. Our
      aim was to investigate the frequency of the alanine (Ala) 54Thr polymorphism of
      the FABP2 gene in patients with coronary heart disease (CHD), and the association
      between the polymorphism and the markers of metabolic syndrome, serum lipid
      levels and the fatty acid profile of serum lipids. METHODS AND RESULTS: A total
      of 414 CHD patients (mean age 61 years, range 33-74) participated in the cross
      sectional EUROASPIRE (European Action on Secondary Prevention through
      Intervention to Reduce Events) Study. Markers of metabolic syndrome included
      fasting plasma glucose concentration, serum high-density lipoprotein cholesterol
      and triglycerides (TG), waist circumference, the waist/hip ratio, body mass index
      (BMI) and blood pressure (BP). The frequency of the Thr54 allele was similar in
      the CHD patients (27.2%) and control subjects from two independent studies (27.8%
      and 28.7%). There were no significant differences in plasma glucose, serum
      lipids, BP, BMI, waist circumference or waist/hip ratio among the genotypes.
      Genotype frequency was not associated with the prevalence of diabetes or
      metabolic syndrome, but metabolic syndrome (as defined by National Cholesterol
      Education Program criteria) tended to be more frequent in subjects with the
      Thr/Thr genotype (p = 0.095). There were no differences in the fatty acid
      profiles of serum cholesteryl esters, TG or phospholipids among the genotypes.
      CONCLUSIONS: The Ala54Thr polymorphism of the FABP2 gene is not associated with
      CHD, markers of the metabolic syndrome, or the fatty acid profile of serum lipids
      in Finnish CHD patients.

PMID- 12189906
TI  - Plasma leptin measurements in epidemiological investigation: comparison of two
      commonly used assays and estimate of regression dilution bias.
AB  - BACKGROUND AND AIM: As leptin is the object of intensive clinical research, we
      compared the radio-immunological assay (RIA) and enzyme-linked immunosorbent
      assay (ELISA) commercially available for measuring its plasma concentration in
      humans (Study 1), and sought to determine the power of a single plasma leptin
      measurement to characterise adequately a subject within a population on the basis
      of its intra- and inter-individual variations (Study 2). METHODS AND RESULTS:
      Study 1--Plasma leptin concentrations were determined by means of RIA and ELISA
      in a sample of 80 males. The measurements obtained using the two methods were
      closely correlated (r = 0.942), but the bias of the means was 21.1 +/- 73.5% (M
      +/- SD, p < 0.001) and indicated that the two assays were not in agreement with
      each other. As expected, there were strong statistical associations between
      plasma leptin and a number of anthropometric indices, but the slopes of the
      regression of leptin concentration was significantly steeper when measured by
      ELISA. Study 2--ELISA was used to measure plasma leptin concentrations in three
      different samples obtained from 12 males and 12 females at two-week intervals.
      The inter-individual variation in plasma leptin was much greater than its intra
      individual variation (the ratio of intra-to inter-individual variance = 0.05 and
      0.04 in males and females, respectively), thus suggesting that a single fasting
      measurement is sufficient to characterise an individual's plasma leptin level
      within a population. CONCLUSIONS: ELISA is at least as effective as RIA in
      measuring plasma leptin, and is fully suitable for epidemiological
      investigations. A single measurement made in the morning and under fasting
      conditions is sufficient to characterise an individual within a population.

PMID- 12189905
TI  - Reproducibility and validity of a short food questionnaire for the assessment of
      dietary habits.
AB  - BACKGROUND AND AIM: Dietary changes such as reducing the consumption of foods
      high in saturated fat, and increasing the daily intake of unsaturated fat, fibre
      and vitamins may have beneficial effects on long-term health. Accurate dietary
      information is essential for dietary counselling. Most of the methods used to
      examine an individual's diet (food records, diet interview, food frequency
      questionnaires) are too complicated and time-consuming for routine clinical use.
      There is a need for a fast and simple tool for food assessment. The aim of this
      study was to evaluate a short and simple food questionnaire for use in clinical
      practice that emphasises the intakes of fat, fibre, fruit and vegetables
      representative of the usual diet of an individual or group. METHODS AND RESULTS:
      A 15-item questionnaire was completed twice on the same day by 111 participants
      in order to study reproducibility, and its validity was checked by comparing the
      results with those of a 7-day food record for 101 subjects. The participants
      reported a positive attitude to the questionnaire. The reproducibility and
      validity studies comparing the sum scores of the questionnaire and food record
      gave correlation coefficients of respectively 0.95 and 0.73, thus indicating good
      agreement. The reproducibility study showed weighted Kappa coefficients ranging
      from 0.97 for milk and snacks to 0.75 for vegetables. In the validity assessment,
      the weighted Kappa coefficients ranged from 0.73 for butter and margarine to 0.14
      0.25 for vegetables, fish and snacks, which is a less satisfactory result. The
      correlation coefficient between the sum score of the questionnaire and the
      percentage of dietary saturated fat was-0.59. CONCLUSIONS: This simple self
      administered questionnaire allows for the rapid assessment of the constituents of
      the usual diet of an individual. It provides a good estimate of dietary fat and
      fibre but is less accurate in terms of the intake of vegetables, fish and snacks.
      It also offers an opportunity to discuss central points in the improvement of
      dietary habits and may be a useful health educational tool in clinical practice.

PMID- 12189907
TI  - Determinants of serum HDL-C level in a Tehran urban population: the Tehran Lipid
      and Glucose Study.
AB  - BACKGROUND AND AIM: Decreased serum high-density lipoprotein cholesterol (HDL-C)
      is one of the most common lipid disorders in patients with coronary artery
      disease (CAD). Existing evidence suggests that every 1 mg/dL decrease in serum
      HDL-C increases the risk of CAD by 2-3%. This study was performed in the year
      2000 to study HDL-C determinants in a Tehran population. METHODS AND RESULTS: We
      studied 9514 subjects (3942 men and 5572 women) aged 20-69 years, who
      participated in the Tehran Lipid and Glucose Study (TLGS), completed a personal
      history questionnaire (especially concerning physical activity and cigarette
      smoking), and underwent a clinical examination including anthropometric and blood
      pressure measurements. Serum total cholesterol, triglyceride and HDL-C levels
      were measured, and OGTT was used to define diabetic patients according to WHO
      criteria. The women had a significantly higher mean HDL-C level than the mean (45
      +/- 11 vs 38 +/- 9 mg/dL; p < 0.001); low HDL-C levels (< 35 mg/dL) were observed
      in 31% of the men and 13% of the women (p < 0.001). Obese subjects (BMI > or = 30
      kg/m2) had a significantly lower HDL-C level than the normal subjects (42 +/- 11
      vs 44 +/- 11 mg/dL: p < 0.001), and those with truncal obesity (WHR > or = 0.95
      in men and > or = 0.8 in women) lower HDL-C levels than the normal subjects (37
      +/- 9 vs 39 +/- 10 mg/dL in men and 44 +/- 11 vs 42 +/- 11 mg/dL in women; p <
      0.001 for both). Smokers had a significantly lower HDL-C level than non-smokers
      (38 +/- 10 vs 43 +/- 11 mg/dL; p < 0.001) and a low HDL-C level was twice as
      common (36.4 vs 18.2%). Passive smokers also had lower HDL-C levels (42 +/- 11 vs
      43 +/- 11 mg/dL; p < 0.001). Mean serum HDL-C was significantly lower in
      hypertriglyceridemic than those with normal triglycerides levels (men: 4 +/- 8 vs
      40 +/- 9 mg/dL, p < 0.001; women: 40 +/- 10 vs 47 +/- 11 mg/dL, p < 0.01). Mean
      HDL-C levels were similar in subjects with different degrees of physical
      activity, as well as between diabetics and non-diabetics and hypertensive and
      normotensive subjects. Multiple stepwise regression analysis showed that the
      determinants of serum HDL-C levels were, in order of entering the model:
      hypertriglyceridemia (OR 3.4, p < 0.001), male sex (OR 3.1, p < 0.001), cigarette
      smoking (OR 1.7, p < 0.001), obesity (OR 1.4, p < 0.01), age (OR 0.9, p < 0.05),
      high WHR (OR 1.2, p < 0.05), and passive smoking (OR 1.1, p < 0.05). Physical
      activity, hypertension, and diabetes mellitus did not enter the predictive model.
      CONCLUSION: Apart from age and sex which are constitutional, and unmodifiable
      variables, the determinants of HDL-C level (hypertriglyceridemia, obesity,
      truncal obesity, cigarette smoking, and passive smoking) can be used in community
      CAD prevention programmes.

PMID- 12189908
TI  - Lipoprotein transport and metabolism: a brief update.

PMID- 12189909
TI  - Control of post-prandial hyperglycemia--an essential part of good diabetes
      treatment and prevention of cardiovascular complications.
AB  - AIM: This article reviews the relationship between the control of post-prandial
      hyperglycemia and diabetes-related complications. DATA SYNTHESIS: Hyperglycemia
      is a modifiable risk factor that has a deleterious effect on the development and
      progression of microvascular and macrovascular complications in patients with
      type 2 diabetes. The UK Prospective Diabetes Study revealed how reductions in
      hemoglobin A1c (HbA1c) correlate with a significant reduction in all-cause
      mortality and the incidence of myocardial infarction. The Diabetes Intervention
      Study showed that poor control of fasting glycemia does not increase the risk of
      myocardial infarction or mortality, whereas poor control of post-prandial glucose
      is associated with a high all-cause mortality rate. HbA1c is the standard measure
      for metabolic control and therapeutic efficacy, but does not reflect fluctuations
      in glycemic control. Plasma glucose concentrations in healthy subjects remain
      within a narrow range, which suggests that the fluctuations in glucose levels
      caused by inappropriate treatment may have negative consequences. These
      fluctuations have been associated with acute adverse effects (particularly
      excessive post-prandial hyperglycemia, pre-meal hypoglycemia and weight gain)
      that counteract the positive effect of lowering fasting plasma glucose and HbA1c.
      Post-prandial hyperglycemia and spikes also have deleterious effects on insulin
      secretion and sensitivity. Prandial oral antidiabetic agents such as alpha
      glucosidase inhibitors (acarbose, miglitol) and rapidly acting insulin
      secretagogues (nateglinide, repaglinide) have recently been introduced to improve
      the control of post-prandial hyperglycemia. CONCLUSION: Near-normal post-prandial
      glycemic control is associated with lower rates of cardiovascular and all-cause
      mortality than excessive post-challenge hyperglycemia. In addition to the
      aggressive control of HbA1c and fasting plasma glucose, the strict normalisation
      of postprandial hyperglycemia is an essential part of good diabetes treatment.
      There is growing evidence from epidemiological and clinical studies that this
      also reduces the risk of cardiovascular complications.

PMID- 12189910
TI  - The gamma knife for relief of trigeminal neuralgia.

PMID- 12189911
TI  - Looking back: punctured wounds of the knee-joint in 1915.

PMID- 12189912
TI  - Talking to patients about tort reform--Part I.

PMID- 12189913
TI  - Our medical staff has a physician returning to us after completing treatment for
      chemical dependency.

PMID- 12189914
TI  - [Cellular and molecular mechanisms of neoplasms treatment].

PMID- 12189915
TI  - [Role of white cells and neoplastic cells in haemostasis].
AB  - The aim of this review was to assess the role of white cells and neoplastic cells
      in haemostasis.

PMID- 12189916
TI  - [Differential diagnosis of immune abnormalities in hematologic malignancies].

PMID- 12189917
TI  - [Fungal infections in immunosuppression--course, diagnosis and therapy].

PMID- 12189918
TI  - [Immunological status post megachemotherapy and hematopoietic cell
      transplantation].

PMID- 12189919
TI  - [Oncogene products inhibitors in the treatment of cancer].

PMID- 12189920
TI  - [Monoclonal antibodies in hematologic oncology].

PMID- 12189921
TI  - [Perspectives for the use of gene therapy in blood disorders].

PMID- 12189922
TI  - [Estimation of "total" parathyroid hormone molecule (PTH-84)--diagnostic and
      therapeutic aspects].

PMID- 12189923
TI  - [Risk factors of fractures in osteoporosis].

PMID- 12189924
TI  - [The role of sympathetic system in the pathogenesis of primary hypertension].

PMID- 12189925
TI  - [The significance of the inhibition of increased sympathetic activity in renal
      diseases].

PMID- 12189926
TI  - [Contemporary diagnosis of increased sympathetic activity: the ups and downs].

PMID- 12189927
TI  - [How to treat effectively hypertensive patient with overactivity of sympathetic
      system?].

PMID- 12189928
TI  - [Low-protein diet and the progression of renal disease: benefits and risks].

PMID- 12189929
TI  - [The significance of hypolipemic drugs in the inhibition of progression of renal
      failure].

PMID- 12189930
TI  - [Anemia and progression of renal failure].

PMID- 12189931
TI  - [ACE and AT1 inhibitors in used in the progression of chronic renal failure].

PMID- 12189932
TI  - [Does erythropoietin restrict lef ventricular hypertrophy in patients with
      chronic renal failure?].

PMID- 12189933
TI  - [Report of the activities of Warsaw-Lodz Branch of the Polish Society of
      Nephrology 1995-2001].

PMID- 12189934
TI  - [Abstracts of papers presented and discussed at the two meetings of the
      Nephrological Commission of the Clinical Pathophysiology Committee of the Polish
      Academy of Science. Warszawa, 13 December 2000 and 15 February 2001].

PMID- 12189941
TI  - Language...

PMID- 12189943
TI  - Research fraud.

PMID- 12189944
TI  - DVT prophylaxis in the perioperative setting.
AB  - This is the first of a two-part article in which Agnes Arnold examines the role
      of the perioperative nurse in the prophylaxis of lower limb deep vein thrombosis
      (DVT). This part discusses the pathophysiology of DVT and the methods of
      assessing an individual's risk of developing the disorder. Part 2, which will
      appear in the September edition of BJPN, will deal with prophylaxis of DVT. It
      will critically analyse the research, cost-effectiveness, side-effects and target
      patient population of each prophylactic regimen.

PMID- 12189945
TI  - The benefits of e-learning.
AB  - Everything has 'e' in front of it these days--and training and education is no
      different. The growth of information technology and especially the web has led to
      us doing all sorts of different activities via our computers. There is now a
      plethora of e-learning opportunities--from helping your children prepare for
      their GCSEs to degree courses on line. So why have NATN decided to invest in e
      learning for the members?

PMID- 12189946
TI  - Animal health and foodborne pathogens: enterohaemorrhagic O157:H7 strains and
      other pathogenic Escherichia coli virotypes (EPEC, ETEC, EIEC, EHEC).
AB  - The majority of interactions between microorganisms and animals are based on
      convenient relations for both of them. Symbiotic microorganisms, like intestinal
      microbiota, produce important vitamins for animals and protects them from
      putative pathogens. In general, for monogastric animals, the main contribution of
      intestinal microorganisms is to supply with growth factors the animal diet, and
      in some cases they are responsible for providing essential vitamins (e.g. vitamin
      K). Some particular and relatively few microbes like viruses, bacteria, fungi,
      protozoa and algae are responsible for animal illness. Because microorganisms are
      easily dispersed, display physiological diversity, and tolerate extreme
      conditions, they are ubiquitous and may contaminate and grow in many products,
      including food and raw materials. Foodborne diseases are caused by consumption of
      contaminated food or beverages. Many different disease-causing pathogens can
      contaminate food, so there are many different foodborne infections. In addition,
      poisonous chemicals and biological toxins can cause disease if they are present
      in food. To know how a particular disease is spreading is an important matter to
      take appropriate steps to stop it. For example Escherichia coli O157:H7
      infections can spread through contaminated food (meat, vegetables, cheese, etc.),
      contaminated drinking water or juices, contaminated swimming water and from
      person to person. Among foodborne pathogens, the most frequently detected are
      bacteria, but also parasitic protozoa and worms, viruses, natural toxins and
      other pathogenic agents like prions are important agents for foodborne diseases.
      Particular pathogenic types of E. coli, classified by their specific pathogenic
      mechanisms (toxins, adhesins, invasiveness, etc.) are actually known as E. coli
      virotypes. Enterohaemorrhagic E. coli (EHEC), which constitute the main part of
      this review, were also named verotoxigenic E. coli (VTEC) or Shiga toxigenic E.
      coli (STEC). EHEC strains cause haemorrhagic colitis (HC), haemolytic uremic
      syndrome (HUS) and thrombotic thrombocytopaenic purpura (TP) in humans. They
      synthetize shigatoxins (verotoxins) which are potent cytotoxic substances,
      adherence factors and enterohaemolysin. EHEC are responsible for many outbreaks
      of bloody diarrhoea caused by contaminated foods: beef, milk, fruits, juice,
      water, etc. The most important serogroups among EHEC are O26, O111 and O157,
      being O157:H7 the most relevant serotype in foodborne outbreaks. The normal
      intestinal microflora of cattle was found to be the most relevant reservoir of
      EHEC strains.

PMID- 12189947
TI  - Zearalenone--undesirable substances in feed.
AB  - The main arguments, discussed by different international organizations, which
      confirm the significance of problems connected with the presence of zearalenone
      in animal feed materials and their influence on the safety of food materials are
      shown in this review article. The main world research trends focused on
      zearalenone, as undesirable substances, are also presented. A variety of Fusarium
      fungi produce a number of different mycotoxins, for example zearalenone. Is not
      true that Fusarium fungi are they the most prevalent toxin-producing fungi only
      in the northern temperate regions, are also commonly found on cereals grown in
      the temperate regions of America, Europe and Asia. Zearalenone have been shown to
      cause a variety of toxic effects in both experimental animals and livestock, and
      have also been suspected of causing toxicity in humans. Zearalenone is a stable
      compound, both during storage/milling and the processing/cooking of food, and it
      does not degrade at high temperatures. Studies of metabolism indicate that
      zearalenone is fairly rapidly absorbed following oral administration, with the
      formation of alpha- and beta-zearalenol and alpha- and alpha-zearalanol, which
      are subsequently conjugated with glucuronic acid. This mycotoxin and some of
      these metabolites have been shown to competitively bind to estrogen receptors in
      a number of in vitro systems. Binding to specific receptors has been demonstrated
      in the uterus, mammary gland, liver and hypothalamus of different species.
      Additionaly alterations of immunological parameters were found at high
      zearalenone concentrations in vitro. Zearalenone causes alterations in the
      reproductive tract of laboratory animals and domestic animals. Various estrogenic
      effects such as decreased fertility, increased embryolethal resorptions, reduced
      litter size, changed weight of adrenal, thyroid and pituitary glands and change
      in serum levels of progesterone and estradiol have been observed, and teratogenic
      effects were found in pigs and sheep. It may be that the safety of zearalenone
      could be evaluated on the basis of the dose which had no hormonal effects in
      pigs, the most sensitive species, and a temporary Tolerable Daily Intake for
      zearalenone of 0.2 microgram/kg of body weight, could be established.

PMID- 12189948
TI  - Contaminants in feed for food-producing animals.
AB  - Outbreaks of Bovine Spongiform Encephalopathy (BSE) and food borne microbial
      infections, dioxin contaminated animal products, the presence of veterinary drug
      residues, microbial resistance to antibiotics, mycotoxins, agricultural and
      industrial chemicals, etc. are serious concerns for the food industry in many
      countries. Since the direct links between feed safety and safety of foods of
      animal origin are obvious, feed production and manufacture should be considered
      as an integral part of the food production chain. Industry is responsible for the
      quality and safety of food and feed that is produced. This paper is a brief
      review of some microorganisms as source of infections for farm animals that could
      result in human illnesses. These include Salmonella enterica, Bacillus anthracis,
      Toxoplasma gondii, Trichinella spiralis, prions, Listeria monocytogenes, EHEC,
      Campylobacter, Clostridium botulinum, Hog Cholera virus, Foot and Mouth Disease
      virus, etc. as well as other contaminants associated with animal feed such as
      mycotoxins, veterinary drugs, dioxins and PCB and Genetically Modified Organisms.

PMID- 12189950
TI  - The prevalence of green muscle disease in turkeys from the Warmia and Mazury
      province of Poland.
AB  - The green muscle disease (GMD), described for the first time in 1968, is a cause
      of significant losses in the production of turkey meat. Pathological changes of
      different intensity are found in smaller pectoral muscles on one or both sides of
      the sternal crest. GMD has been more frequently observed in Poland since 1991 in
      breeding turkeys of heavy and medium-heavy types assigned to slaughter after
      completing the reproductive period. The present study deals with the occurrence
      of this disease in the Warmia and Mazury District of Poland. Characteristic green
      foci located in small pectoral muscles were found in 4090 out of 26,169
      slaughtered turkeys, i.e. in 15.63% of the carcasses investigated. It was
      established that 2430.5 kg of meat were confiscated what gave 0.59 kg of
      confiscated meat per head on the average.

PMID- 12189949
TI  - Characterization of Escherichia coli strains associated with canine pyometra.
AB  - The purpose of this study was to characterize E. coli isolates from canine
      pyometra which were isolated in pure culture. The E. coli strains were obtained
      in 128 cases, from 143 animals which were submitted to ovariohisterectomy.
      Biochemical analysis of all strains examined was possible on separation of 10
      primary biotypes. The majority of the strains (87.5%) belonged to biotype 9, 1,
      13 and 15. Dulcitol was fermented by 93% of all isolates. Haemolysin and colicin
      production was found in 53.9% and 26.6% of the strains, respectively.
      Approximately 37% of strains expressed resistance to two or more antibacterial
      agents. No plasmid was detected in 4.6% of the isolates. Plasmid profiles of all
      plasmid-containing isolates revealed plasmid bands corresponding to molecular
      weight ranging from 1 kb to 160 kb. Many of the strains examined had a single
      plasmid of 110 kb (46.1%), or two plasmids 110:65 kb (18.8%). Both plasmids
      appearing alone or in combination with other plasmids were detected in 90.1% of
      isolates with plasmid content. It was established that among haemolytic,
      colicinogenic and motile strains, the presence of both plasmids was 91.3, 94.1
      and 91.4%, respectively. The appearance of both plasmids among dulcitol-positive
      and raffinose-negative strains was estimated at 88.2 and 88.3%, respectively. In
      a group of colicinogenic strains the presence of a single plasmid of molecular
      weight 110 kb was estimated at 5.9%. When both plasmids were present (profile
      110:65), the percentage of these strains was 70.6%.

PMID- 12189951
TI  - Histopathological changes in green muscle disease of turkeys.
AB  - In this study, results of histopathological investigations of meat samples
      collected from turkeys with macroscopically recognized green muscle disease were
      compared with those obtained from turkeys without macroscopic signs of this
      syndrome. The histopathological lesions were assessed based upon the self
      designed 7-grade scale of the intensity of changes. The greatest intensity of the
      histopathological alterations were found in the smaller pectoral muscle collected
      from turkeys in which macroscopical signs of the green muscle disease were
      observed. Similar changes were also found in the greater pectoral muscle,
      however, they were less intense than those determined in the smaller pectoral
      muscle.

PMID- 12189952
TI  - The use of chosen serological diagnostic methods in Lyme disease in horses. Part
      I. Indirect immunofluorescence and enzyme-linked immunosorbent assay (ELISA).
AB  - The investigations aimed to establish the reliability of the chosen serological
      tests designed for the diagnosis of Lyme borreliosis in horses. The
      investigations were carried out in five Horse Breeding Centres (OHK). Statistical
      analysis methods were used to determine sample size for particular centres:
      Krasne (Kr)--49, Lack (L)--21, Walewice (W)--111, BogusLawice (B)--17, Kozienice
      (K)--61. The experimental material comprised the chosen horses from which blood
      samples were collected in order to obtain sera. The test used for indirect
      immunofluorescence assay (IFA No 75941, Bio-Merieux) is commercially designed for
      the investigation of human sera and thus needed a prior species adaptation and
      standardization; ELISA (MRL DIAGNOSTICS, No EL0400G) which was also species
      adapted and stardandized and ELISA commercially assigned for the examination of
      dog or horse sera (Die System Diagnostica GmbH Borrelia burgdorferi Veterinary
      ELISA No. 122.00 Genzyme Virotech GmbH). In the IFA test the highest share of
      positive results was obtained in respect of the sera from OHK in (K)--60.7% and
      then in (B)--52.9%, (L)--42.9%, (W)--40.5%, (Kr)--38.7%. In the standardized
      ELISA the highest percent of positive results, amounting to 33.3%, was obtained
      in respect of the sera from (L), and then from (W)--20.7%, (K)--11.5%, (Kr)-
      10.2% and (B)--5.9%. The percent of positive results obtained in the commercial
      ELISA also agreement on a high level: the sera originating from (W) were positive
      in 18.9%, from (K)--9.8%, (L)--9.5%. (B)--5.9% and (Kr)--4.1%. Both ELISAs showed
      high agreement although the standardized test was characterized by a greater
      tendency for suggesting the presence of B. burgdorferi infection and the
      agreement of these two ELISAs with the IFA was not so strong. The IFA showed the
      highest tendency for suggesting the presence of the B. burgdorferi infection,
      being characterized by the highest percent of false positive results.

PMID- 12189953
TI  - The use of chosen serological diagnostic methods in Lyme disease in horses. Part
      II. Western blot.
AB  - In this investigation the Western blot test was treated as a method verifying
      results of the IFA, commercial ELISA and standardized ELISA tests (described in
      Part I). The verifying investigations were performed on 82 serum samples, which
      in the commercial ELISA were positive in 36 cases, dubious in 31 cases and
      negative in 15 cases as well as on 5 serum samples obtained from horses infected
      with Leptospira spp., which in the ELISA commercial were dubious (total of 87
      sera samples). The antigens, against which the immunological response in horses
      was directed, were also established. The Milenia--Blot--Borrelia IgG test (MIDBO
      IgG-Kit 30 TESTS: DPC Bierman GmbH) was used in the investigation. In view of
      species differences, rabbit anti-horse IgG (whole molecule) alkaline phosphatase
      conjugate, no A6063 SIGMA-ALDRICH was used interchangeably. Also the control sera
      were substituted with the horse control sera. It was demonstrated that the
      Western blot test is the most reliable in the serological diagnosis of B.
      burgdorferi infection in horses. The commercial ELISA and standardized ELISA
      tests represent a lower diagnostic value than the Western blot test, although
      similar to each other, while the value of the IFA is minimal. In the Western blot
      test antigens were established against which the immunological response in horses
      in mostly directed. In the sera evaluated in this test as positive the presence
      of antibodies, mainly against antigens with the following molecular weights: 41
      kDa, 62/60 kDa, 93 kDa, 72 kDa, 34 kDa (OspB), 66 kDa was noted. At the same
      time, antibodies contained in the sera accepted as negative, in 55.5% cases also
      reacted with the antigen of 41 kDa. It points to its minimal specificity. On the
      basis of the results obtained it is recommended that serological examination of
      horses should be with the ELISA and that positive or dubious results should be
      verified with the Western blot test.

PMID- 12189954
TI  - Fluorometric assessments of viability and mitochondrial status of boar
      spermatozoa following liquid storage.
AB  - A study was conducted to assess viability and mitochondrial status of boar
      spermatozoa stored at 5 degrees C and 16 degrees C. Gel-free ejaculates,
      collected from 3 mature boars, were extended in a standard diluent (K3)
      supplemented with a low-density lipoprotein fraction (LDF) isolated from egg
      yolk, and stored for 96 h at 5 degrees C and 16 degrees C. Motility analysis was
      conducted after semen dilution (D0) and on D1-D4 of storage. A double staining
      method, rhodamine 123 (R123) and propidium iodide (PI), was used to assess sperm
      viability and mitochondrial status. Sperm viability was also assessed using
      Hoechst 33,258 (H33258) stain. In fresh semen samples, the percentage of motility
      was significantly correlated with the percentage of viable spermatozoa with
      functional mitochondria (R123-PI), viable spermatozoa determined by H33258
      staining and ATP content (r = 0.88, p < or = 0.01; r = 0.69, p < or = 0.05; r =
      0.77, p < or = 0.01, respectively). The ATP content was also positively
      correlated with the percentage of viable spermatozoa with functional mitochondria
      (r = 0.76, p < or = 0.01). Sperm cells progressively lost motility, viability and
      mitochondrial capacity when stored in the supportive media at 5 degrees C and 16
      degrees C. Motility estimates were lower (p < or = 0.05) than the percentage of
      viable spermatozoa with functional mitochondria during storage in K3 and LDF
      based diluents on D4 and D3-D4, respectively. Deterioration in motility and
      membrane integrity was less marked in spermatozoa stored in LDF-based diluents.
      Spermatozoa doubly-stained with R123-PI appeared to possess some functional
      mitochondria, particularly in LDF-based diluent semen. Estimates of sperm
      viability, as determined by R123-PI staining, were equivalent (p > or = 0.05) to
      estimates made using H33258 staining. A decrease in mitochondrial activity, as
      measured by R123 uptake, was accompanied by lower ATP content in spermatozoa
      stored in K3 and LDF-based diluents after 48 h and 72 h of storage, respectively.
      Fluorometric measurements of viability and mitochondrial status of boar
      spermatozoa during liquid storage seem to provide reliable information about the
      sperm functional membranes.

PMID- 12189955
TI  - Evaluation of morphological lesions in selected internal organs in lambs of
      Kamieniecka, Pomorska and Polish Blackheaded Mutton sheep and their crossbreeds.
AB  - Investigations were carried out on 40 rams aged 50 days (n = 8), Kamieniecka (K),
      Pomorska (P) and Polish Blackheaded Mutton (PBM) breeds and their crossbreeds (K
      x PBM, P x PBM). Microscopic evaluation of the liver, kidneys, spleen and heart
      muscle in the rams as well as ultrastructural analyses of their liver and
      semitendinous muscle showed that retrogressive lesions, circulation disturbances,
      inflammation and progressive changes occurred respectively: frequently,
      occasionally, rarely. Internal organs, particularly liver and kidneys, of
      crossbred rams (K x PBM and P x PBM) were almost two times more affected with
      morphological lesions than purebred lambs (K and P). However, in the
      semitendinous muscle these differences were more vivid in the ultrastructural
      analysis than in the histopathological or macroscopic observations. Results
      suggest that breed growth-rate differences have effects on the pathomorphological
      pattern of the liver and kidneys in lambs. On the bases of this evaluation, it
      can also be emphasised that young PBM rams are less susceptible to morphological
      lesions than the K and P breeds.

PMID- 12189956
TI  - Pathogenicity of the microorganisms of the family Chlamydiaceae respecting the
      changes in their classification.
AB  - The comparison of names of the species before the reclassification of the family
      Chlamydiaceae into two genera with the species names acknowledged at present is
      presented. The pathogenicity of these species for animals and man is
      characterised.

PMID- 12189957
TI  - Biological warfare and bioterrorism.

PMID- 12189958
TI  - Quick reference guide to biological warfare.

PMID- 12189959
TI  - The Georgia Emerging Infections Program: monitoring trends in invasive
      pneumococcal disease.
AB  - The active, population-based surveillance system of the Georgia EIP has provided
      valuable insights into the characteristics of invasive pneumococcal disease in
      Georgia and continues to provide an important mechanism to assess the impact of
      the newly introduced PCV7 vaccine. The problem of antimicrobial resistance has
      been carefully documented among isolates from invasive pneumococcal disease in
      all age groups, particularly young children. Fluoroquinolone resistance is now
      present in our area and will require close monitoring in the coming months and
      years. Over 80% of invasive pneumococcal disease and over 85% of penicillin and
      cefotaxime resistant invasive disease occurring in young children in our
      surveillance area involve serotypes included in the new conjugate vaccine
      approved for use in children. Preliminary data suggest an early decline in
      invasive pneumococcal disease in young children has occurred since the
      introduction of the conjugate vaccine and the effect upon the prevalence of
      antimicrobial resistance remains to be determined. The high rates of invasive
      pneumococcal disease, the significant associated morbidity and mortality and
      antimicrobial resistance highlight the need for enhanced prevention measures in
      both adults and children. Ongoing surveillance in the Georgia EIP will allow
      accurate measurement of the impact of prevention efforts, provide essential
      information on trends in antimicrobial resistance and document any changes in the
      pneumococcal serotypes responsible for invasive disease in the conjugate vaccine
      era.

PMID- 12189960
TI  - Combating antibiotic resistance: expanding the role of the clinician.

PMID- 12189961
TI  - Can accurate immunization rates be determined in a primary care clinic?
AB  - Based on the data that we collected in our clinic, we were unable to determine
      the immunization rates of our patients accurately. Despite multiple telephone
      calls to families and health departments and an exhaustive chart review, 87 of
      the 261 families studied could not be contacted, thereby making an analysis of
      immunization data impossible. Another technique of tracking immunizations, such
      as a statewide or national registry, is needed to obtain accurate immunization
      data.

PMID- 12189962
TI  - Progress report--Georgia Immunization Registry.

PMID- 12189963
TI  - Arboviruses in Georgia. Emergence of West Nile Virus.

PMID- 12189965
TI  - Foodborne illnesses: epidemiologic considerations.

PMID- 12189964
TI  - The epidemic of HIV/AIDS in middle Georgia.

PMID- 12189966
TI  - Public health preparedness for bioterrorism.

PMID- 12189967
TI  - Intracardiac echocardiography: from electroanatomic correlation to clinical
      application in interventional electrophysiology.
AB  - Intracardiac echocardiography (ICE), using an ultrasound transducer at the tip of
      a percutaneously placed catheter, has recently been introduced for the
      visualization of the intracardiac anatomy and in order to reduce the fluoroscopy
      time. This review focuses predominantly on the current use of ICE in
      interventional electrophysiology. ICE has been shown to facilitate the targeting
      of specific anatomic landmarks, such as the crista terminalis, the Eustachian
      ridge, the tricuspid annulus, the coronary sinus ostium, and the pulmonary veins
      that cannot be adequately visualized at fluoroscopy. Direct imaging of these
      sites can be advantageous in that it facilitates the accurate guidance of the
      ablative procedure and shortens the fluoroscopy time. ICE has been demonstrated
      to be useful in the positioning and stabilization of the imaging ablation
      catheter, the evaluation of the lesion size and continuity and in the immediate
      identification of complications. Furthermore, in the last few years there has
      been a revival in the use of transseptal catheterization due to a larger
      development of radiofrequency catheter ablation in the left atrium. ICE,
      providing excellent views of the fossa ovalis and of the transseptal apparatus,
      can be safely used to prevent life-threatening complications following
      inadvertent puncture of anatomic structures such as the lateral wall of the left
      atrium or the aortic root. Moreover, ICE appears to be very useful in combining
      true anatomical features with electrical activation in an attempt to construct
      realistic electrical-anatomical maps. Finally, the three-dimensional tomographic
      reconstruction of intracardiac images and the phased array ICE catheter with
      Doppler capabilities seem to be promising tools both for the guidance of ablation
      procedures as well as in leading experimental studies.

PMID- 12189968
TI  - Management of patients with low-risk chest pain at the time of admission: a
      prospective study on a non-selected population from the Emergency Department.
AB  - BACKGROUND: The management of patients with acute chest pain is a common and
      difficult challenge from the epidemiological, clinical, organizational and
      malpractice points of view. Our purpose was to test and implement a simple
      clinical protocol for the management of patients with acute chest pain and at low
      risk for an acute coronary syndrome (ACS) at the time of admission to the
      Emergency Department (ED). METHODS: During a 5-month study period, 570
      consecutive patients were admitted to the ED with acute chest pain: 224 patients
      were excluded owing to the presence of a clear diagnosis of an ACS or of high
      risk factors. The remaining 346 were considered, at the time of admission, as
      being at low risk for an ACS and constituted the study group (208 males, 138
      females, mean age 65 years). These 346 patients were evaluated in the ED area by
      means of multiple ECGs and multiple blood sampling for the creatine kinase-MB
      mass and troponin I serum levels at the time of admission and 6 and 12 hours
      later. In selected cases a treadmill stress test was requested in order to
      further clarify the diagnosis. RESULTS: The ECG at the time of admission was
      normal or nearly normal in 79% of the patients. Stress testing was performed in
      79 patients (25%). Sixty-six/346 low-risk patients (19%) were admitted to the
      coronary care unit during ED observation: 38 patients because of positive
      markers, 10 because of a positive ECG, 13 because of positive markers and ECG,
      and 5 because of a positive stress test. Two hundred and eighty low-risk patients
      without evidence of acute ischemia were definitively discharged and classified as
      having non-ischemic chest pain. At 1 month of follow-up, 1 patient underwent
      coronary artery bypass grafting, 1 patient was again admitted to the ED for acute
      pulmonary edema, and 2 patients had acute extracardiac events. Within 1 year of
      follow-up 4 deaths occurred: 2 were cancer-related and 2 were sudden deaths.
      CONCLUSIONS: The tested strategy, based on integrated clinical, ECG and
      multimarker data, and on a short "test of time" period of low-risk patient
      observation, can allow the identification of patients having an ACS on the one
      hand and of those for whom a safe, rapid and early discharge is possible on the
      other, in a low-cost environment.

PMID- 12189969
TI  - Elective stenting in small coronary arteries: results of the Italian prospective
      multicenter registry MICROSCOPE.
AB  - BACKGROUND: The role of stent implantation in small coronary arteries is still
      controversial. The MICROSCOPE study (Ministenting in small coronary arteries, a
      prospective evaluation) is a multicenter registry addressed to prospectively
      evaluate the immediate and mid-term clinical and angiographic results of elective
      stenting of lesions located in coronary arteries with an angiographic reference
      diameter < or = 2.75 mm. METHODS: A total of 146 patients (160 lesions) were
      included in the study. The percentage of complex lesions (B2 and C lesions) was
      49.3%. The clinical indications for stent implantation were: stable angina
      (55.0%), unstable angina (24.6%), and clinical evidence of myocardial ischemia in
      asymptomatic patients (20.4%); 60% of patients had multivessel disease. Stent
      deployment could be performed in 96.2% of lesions. The baseline reference
      diameter was 2.12 +/- 0.36 mm. In all cases the Ministent (Cordis, a J&J Company,
      Miami, FL, USA), specifically designed for small coronary arteries, was employed.
      The stent was pre-mounted on low profile balloons available in three different
      diameters (2.25, 2.50 and 2.75 mm) and three different lengths (11, 15 e 26 mm).
      RESULTS: The primary endpoint of successful stent-assisted angioplasty in all
      study vessels without major adverse cardiac events was achieved in 95.8% of the
      patients. The minimal lumen diameter increased from 0.64 +/- 0.24 to 2.02 +/-
      0.43 mm and the dimensions of the stenosis (expressed as a percentage of the
      diameter of the coronary vessel) decreased from 68.6 +/- 10.8 to 16.2 +/- 10.7%
      (< 30% standard deviation in all cases). After the procedure all the patients
      received double antiplatelet therapy for 4 weeks. Post-procedural complications
      were limited to 2 patients (1.3%) who had a non-Q wave myocardial infarction at 6
      months of follow-up; 13 patients (11%) required target lesion revascularization.
      No patient died following the procedure. Angiographic control was performed in
      44% of lesions. The minimal lumen diameter decreased to 1.12 +/- 0.47 mm and the
      percent stenosis increased to 45.9 +/- 23.2%. The incidence of binary restenosis
      (stenosis > or = 50%) was 41%. CONCLUSIONS: Elective stenting of small coronary
      arteries with the Ministent can be safely performed and is associated with a low
      incidence of acute or subacute stent thrombosis. The mid-term results indicate a
      high rate of angiographic restenosis but a low need of target vessel
      revascularization. These data suggest that stenting cannot be considered the
      treatment of choice for unselected lesions located in coronary arteries with a
      small reference diameter, but represents a safe solution if unsatisfactory
      results are obtained with balloon angioplasty alone.

PMID- 12189970
TI  - Concealed ventricular extrasystoles. A family of premature ventricular complexes
      with high spontaneous variability.
AB  - BACKGROUND: The term concealed ventricular extrasystoles defines a phenomenon in
      which premature beats have a cyclical distribution and manifest after a
      predictable number of intervening sinus beats. The extent of its spontaneous
      variability as well as the stability of its orderly distribution, however, have
      not been defined yet. The aim of this study was to assess whether there is any
      difference between the variability of concealed ventricular extrasystoles and
      their allorhythmic patterns. METHODS: The distribution of premature ventricular
      complexes (PVCs) was evaluated in 39 patients with frequent monomorphic PVCs (>
      1000/die) during a baseline 24-hour ambulatory monitoring electrocardiogram.
      Patients were divided into two groups: group A had evidence of concealed
      ventricular extrasystoles, while in group B PVCs were randomly distributed. All
      patients underwent a second ambulatory monitoring electrocardiogram within 30-360
      days. RESULTS: The overall number of PVCs did not differ between the groups.
      Patients of group A showed a very high spontaneous variability (p = 0.006)
      between the first and the second ambulatory monitoring electrocardiogram, whereas
      significant differences were not observed among patients of group B. CONCLUSIONS:
      Concealed ventricular extrasystoles are not casual and transient, but should be
      regarded as a marker of a "family" of PVCs that have the tendency either to
      maintain their orderly distribution for long periods or to disappear suddenly.

PMID- 12189971
TI  - The impact of gender on heart transplantation outcomes: a single center
      experience.
AB  - BACKGROUND: According to the data of the Registry of the International Society
      for Heart and Lung Transplantation, donor and recipient female gender is a
      significant risk factor for mortality after heart transplantation. It has also
      been reported that donor-recipient gender mismatch is a determinant of post
      transplant morbidity and mortality. To examine the effect of gender on the early
      and mid-term outcomes, we retrospectively reviewed data of a consecutive group of
      heart transplant recipients at our Institution. METHODS: The study population
      comprised 99 patients undergoing heart transplantation between 1996 and 1998.
      This population was divided into four groups on the basis of donor and recipient
      matching. Group A consisted of 61 men who received male donor hearts, group B of
      12 women who received female donor hearts, group C of 9 women who received male
      donor hearts, and group D of 17 men who received female donor hearts. Standard
      heart transplantation protocols were applied to all patient groups [graft
      preservation with Celsior solution, Shumway surgical technique, donor-recipient
      size matching > or = 1.0, induction therapy with polyclonal antithymocyte
      globulins, triple immunosuppressive therapy (neoral, azathioprine, steroids)].
      RESULTS: The study groups were found to be homogeneous with regard to the major
      preoperative risk factors (etiology, status at transplantation, donor and
      recipient age, total ischemic time). Donor gender, recipient gender and donor
      recipient gender mismatching did not significantly modify the short and mid-term
      survivals, functional recovery and freedom from rejection. CONCLUSIONS: Even
      though previous reports suggest that gender negatively affects survival, this
      factor proved to have no influence on the outcomes of the present series. These
      results can be explained by a correct donor-recipient size matching. The well
      documented female recipients tendency to more frequent and fatal rejection was
      not confirmed in our experience. The patient's age at transplantation, the
      routine use of induction therapy and an aggressive immunosuppressive regimen may
      be the substrate of these findings.

PMID- 12189972
TI  - Combined percutaneous pulmonary valvuloplasty and patent foramen ovale closure in
      an adult with recurrent transient ischemic attacks.
AB  - We report the case of a 60-year-old man with a history of recurrent transient
      ischemic attacks, effort syncope, cyanosis, erythrocytosis and a systolic murmur.
      Echocardiography and catheterization showed severe pulmonary stenosis and a
      patent foramen ovale with a right-to-left shunt. The patient was submitted to
      combined percutaneous pulmonary valvuloplasty and patent foramen ovale closure
      using the Amplatzer device.

PMID- 12189973
TI  - Percutaneous endovascular stent-graft placement for the treatment of acute
      rupture of an aneurysm of the thoracic aorta.
AB  - A 68-year-old male patient presented with massive hematemesis following the acute
      rupture of an aneurysm of the descending thoracic aorta into the esophagus. In
      view of the important cardiac and pulmonary comorbidities, surgical treatment was
      excluded and successful percutaneous implantation of an endovascular stent-graft
      in the descending aorta was performed. In selected patients endovascular
      treatment may constitute an alternative to the surgical repair of ruptured aortic
      aneurysms.

PMID- 12189974
TI  - Propafenone-related cholestatic hepatitis in an elderly patient.
AB  - Hepatic toxicity caused by propafenone is extremely rare. We here describe a case
      of acute cholestasis secondary to propafenone treatment in an elderly male with
      no history of preexistent liver disease. The clinical picture and time course of
      the symptoms seem to be compatible with a direct toxic reaction. Age-related
      delays in hepatic drug metabolism should explain the hazardous increase in the
      bioavailability of this drug. Despite the rarity of this complication,
      propafenone should be considered as a potential cause of drug-induced cholestasis
      in elderly patients. The literature on the hepatotoxicity of propafenone is also
      reviewed.

PMID- 12189975
TI  - Cardiac magnetic resonance imaging diagnosis of a loculated pericardial effusion
      in a patient with a postpericardiotomy syndrome.

PMID- 12189976
TI  - The pharmacological treatment of heart failure: are we looking at the sunset of
      the neurohormonal hypothesis.

PMID- 12189978
TI  - Managing a T-tube.

PMID- 12189979
TI  - How hyperbaric oxygen therapy helps heal chronic wounds.

PMID- 12189977
TI  - Action stat. Ecstasy overdose.

PMID- 12189980
TI  - Poison control center. Administering advice.

PMID- 12189981
TI  - Verbal orders in the O.R. Masking the truth?

PMID- 12189982
TI  - Eliminate the air of mystery from chest tubes.

PMID- 12189983
TI  - In the eye of the beholder.

PMID- 12189984
TI  - Ahead to the past. How genetics is changing your practice.

PMID- 12189985
TI  - High cholesterol (hyperlipidemia).

PMID- 12189986
TI  - Protecting yourself from violence in the workplace.

PMID- 12189987
TI  - How to accurately document i.v. insertion.

PMID- 12189988
TI  - Opening windows? Not an open-and-shut decision.

PMID- 12189989
TI  - Reviewing anxiety and mood disorders.

PMID- 12189990
TI  - Epidural analgesia during labor: lower the risks.

PMID- 12189991
TI  - Understanding biofeedback.

PMID- 12189992
TI  - Myths & facts. ... About Sjogren's syndrome.

PMID- 12189993
TI  - Operating room registered nurses internship program. A recruitment and retention
      strategy.
AB  - The acute nursing shortage, particularly in perioperative nursing, was a driving
      force for the creation of a registered nurse (RN) internship program. The program
      was developed according to the Association of periOperative Nurses (AORN)
      Standards and Recommended Practices and national practice. Program evaluations
      led to positive changes in the program. This article describes the process that
      was followed and the unique features of the program.

PMID- 12189995
TI  - Documentation of characteristics of early hospital readmission of elderly
      patients. A challenge for inservice educators.
AB  - Researchers conducted a retrospective review of 127 hospital records over a 3
      month period to examine factors related to early hospital readmissions of
      patients age 65 and over. The leading diagnoses resulting in early readmissions
      were related to heart and circulatory problems, with a mean of 12.5 days between
      discharge and readmission. Gaps in documentation and the need for including
      qualitative data are discussed. Staff development educators are central to
      implementing strategies to correct these documentation deficiencies.

PMID- 12189994
TI  - Preceptor behaviors integral to the promotion of student critical thinking.
AB  - In the practice setting, preceptors not only contribute to the relational aspect
      of the preceptorship experience but, through their behaviors, they also
      effectively promote the critical thinking ability of students. Through the use of
      a grounded theory method in a recent study, four specific preceptor-generated
      behaviors were identified as integral to the promotion of the critical thinking
      ability of basic baccalaureate nursing students in the practice setting: role
      modeling, facilitation, guidance, and prioritization. In this article, the
      description and meaning of these four behaviors are explored and their
      significance to preceptors and nurse educators who wish to ensure that the
      critical thinking ability of nursing students is fostered in the practice setting
      is discussed.

PMID- 12189996
TI  - Rational nursing: a concept analysis for practical application.
AB  - Rational nursing is a theoretical concept that serves as a practical, behavioral
      application of the nursing process. This article is a concept analysis that
      defines and clarifies rational nursing, examines relational and nonrelational
      propositions, and describes clinical and personal applications for the individual
      nurse. This relatively simple yet revolutionary tool can improve patient outcomes
      and prevent nursing burnout. Nurses involved with staff development, education,
      and retention will discover that teaching and reinforcing rational nursing
      provides nurses with minute-by-minute guidance to the treatment of the human
      response both in patient illness and their own practice of nursing.

PMID- 12189997
TI  - Evaluating the knowledge deficits of registered nurses responsible for
      supervising nursing assistants. A learning needs assessment tool.
AB  - Nurse managers and clinical nurse specialists are constantly seeking ways to
      evaluate the learning needs of nursing staff. Increasingly, nursing assistants
      (NAs) are being employed by healthcare organizations in an effort to provide cost
      effective care. Registered nurses may or may not have the skills necessary to
      supervise NAs. The nurse manager can use this threefold approach to identify
      knowledge deficits of staff members responsible for supervising NAs. Part A
      identifies delegation issues, Part B unveils cognitive deficits, and Part C gives
      the respondents a chance to share their perceived learning needs. Deciding how to
      expend limited resources is a difficult task for the nurse educator. This tool
      provides justification and direction for continuing education programs and other
      planned learning experiences.

PMID- 12189998
TI  - What do nurses know about teaching patients?
AB  - A quasiexperimental study was conducted to ascertain what nurses know about
      teaching patients and whether a planned education offering could increase the
      knowledge nurses have about the teaching process in patient education. A
      convenience sample of 44 nurses participated in a pretest/posttest and 1- to 2
      month follow-up test on the teaching process. Knowledge deficit was present and
      learning evident. Nurse educators should instruct staff on the teaching process,
      giving nurses the necessary skills to deliver effective patient education.

PMID- 12189999
TI  - What rewards do clinical preceptors in nursing think are important?
AB  - This article explores the use of preceptors for a capstone course in a
      baccalaureate curriculum. Nursing faculty, nursing managers, and staff educators
      from local hospitals developed a survey to determine the range of items that
      would serve as recognition or rewards for staff working in a preceptor role. The
      challenge was to identify rewards that are meaningful to the preceptors and
      financially feasible for the organization and the School of Nursing.

PMID- 12190000
TI  - The magnetic pull: recognizing excellence in nursing services.

PMID- 12190001
TI  - [Non-fatal systemic reactions caused by immunotherapy and skin tests].
AB  - OBJECTIVE: The frequency and severity of systemic reaction (SR) from skin test
      (ST) and specific immunotherapy (SIT) in Mexico, have not been published before.
      In order to know that frequency and severity, a prospective study was performed
      in the Allergy Clinic at General Hospital of Matamoros from August, 1991 to July,
      1996. SR from ST and SIT were monitored. Symptoms were recorded with respect to
      the time of onset, involvement of respiratory tract or skin and presence of
      hypotension. RESULTS: 65,397 injections were given to 1,149 patients; there were
      25 SR in 20 patients (1:2,615 injections or 1:57 patients). Time of onset was
      between 10 and 30 minutes. SR were present more frequently during maintenance.
      There was a 3:1 rate in female patients and a predominance in the 15 to 24 age
      group. CONCLUSIONS: In Matamoros, Tamps., Mexico, frequency and severity of SR
      from ST and SIT is not different from published data. Small children are not in
      higher risk. Immunotherapy is a safe therapeutic procedure on expert hands.

PMID- 12190002
TI  - [Hypersensitivity detected by skin tests to food in allergic patients in the
      Hospital Infantil de Mexico Federico Gomez].
AB  - BACKGROUND: The prevalence of food allergy depends on the feeding practices of
      different parts of the world. Peanuts and nuts cause a great part of allergies in
      the United States; in Spain and Portugal are commonly due to fish, milk; in Italy
      seafood and mustard in France. In Mexico we don't know the frequency of food
      allergy and involved groups of age or specific foods. OBJECTIVE: To determine the
      frequency of immediate hypersensitivity for foods in allergic children from
      Hospital Infantil de Mexico Federico Gomez. MATERIAL AND METHODS: A retrospective
      study was performed between January 1995 to December 1999. The skin prick test
      (SPT) to food was reviewed according to Aas classification. Male and female from
      12 months to 18 years old were reviewed. RESULTS: We documented 1,419 patients
      with allergy. Of them 442 (31%) had positive skin prick test (SPT) to some of the
      33 tested foods. The average age of the study group was of 12.8 years. The most
      affected was from 4 to 7 years (49%); the second group from 1 to 3 years with
      23.7%, and the third was from 12 to 17 years with 13.5%. Fish, milky, seafood,
      soy, beans, orange, onion, tomato, chicken, nut, lettuce and strawberry, were
      responsible for 58% of the total of allergic reactions. Of those fish, milk,
      seafood, soy and orange (39%) had the highest frequency. Hypersensitivity to
      several foods is low, finding just one allergen in 50% of the cases, two
      allergens in 25%, three allergens in 9%, four in 7%, five in 5% and more than 6
      only in 3% of cases. CONCLUSION: We concluded that almost any kind of food
      reaction seen in our study was due to alimentary habits of different populations,
      socioeconomic status, and availability of foods. This indicates the diversity of
      costumes in Mexican people due to the wide geographical area and cultural
      background of our country. Results could be increased because of only 33
      allergens were tested.

PMID- 12190003
TI  - [Preeclampsia-eclampsia: a change in utero-placental microcirculation.
      Immunologic, histologic, and biochemical features].
AB  - BACKGROUND: To know the alterations in the microcirculation of the placenta,
      umbilical cord, as well as the immune and hemorrheologic disorders in
      preeclampsia-eclampsia. MATERIAL AND METHODS: Two groups were conformed, 30
      patients each, all of them with pregnancy of more than 24-week gestation. Group A
      included patients with preeclampsia-eclampsia and group B (control group)
      included women with normal pregnancy. In all patients determinations of levels of
      platelets, fibrinogen, antinuclear antibodies, IgG and IgM anticardiolipin, VDRL
      were made; clotting times were determined, and histopathologic analyses
      (placenta, umbilical cord and uterus-placenta membranes) were performed. RESULTS:
      Platelet levels in the group A were normal in 40% and low in 60%. In group B they
      were normal in 83.3% and low in 16.7%. with p < 0.05. In group A fibrinogen was
      normal in 10% and high in 90%; in the group B it was normal in 62.1% and high
      37.9%, with p < 0.05. In group A prothrombin time (PT) was normal in 40% and high
      in 60%; in group B it was normal in 76.7% and low in 23.3%, with p < 0.05. in
      group TPT was normal in 36.7% and high in 62.1%, with p > 0.05. VDRL was negative
      in the 100% of the women of group A and positive in the 3.3% of the controls with
      p > 0.05. The antinuclear antibodies were positive in 6.7% in group A, and in
      23.3% in group B, p < 0.05. IgG anticardiolipin antibodies were negatives in the
      100% in both groups and IgM antibodies were negative in 96.7% in the group B and
      3.3% in group A, p > 0.05. Analysis of histopathologic and immune changes did not
      show statistic significance when comparing both groups. CONCLUSIONS: Statistical
      and clinical significance was observed only in the hemorrheologic changes (PT,
      TPT, fibrinogen and platelets) and in the newborn weight.

PMID- 12190004
TI  - [Asthma: prevalence, pathogenesis and perspectives on new treatments].
AB  - Asthma is a complex clinical syndrome with many phenotypes in both children and
      adults. Its major characteristics include airway inflammation and obstruction,
      bronchial hyper-responsiveness. The disease has its roots in infancy, and both
      genetic and environmental factors contribute to its inception and clinical
      evolution. The prevalence of asthma in increasing around the world. Hypotheses
      that attempt to explain the rising prevalence have been advanced but remain
      unproven. To understand its pathogenesis it is essential to identify factors that
      modulate or intensify the inflammatory response of the airways. The association
      of allergic asthma with immune responses mediated by TH-2 cells and IgE
      antibodies has came to the forefront of medical research. Significant advances in
      understanding the immunology of asthma are being translated into specific
      therapies, some of which hold promise for disease modification.

PMID- 12190005
TI  - [Bronchial foreign body as a differential diagnosis for asthma. Report of a case
      and review of the literature].
AB  - The aspiration of foreign bodies into the airway is a common problem in
      childhood, mainly in children younger than 10-years old. Foreign bodies located
      in the tracheobronchial tree can cause episodic cough, dyspnea and wheezing, and
      generate a misdiagnosed of asthma if physicians do not consider the possibility
      of a bronchial foreign body as a differential diagnosis of this disease. In these
      cases, chest X-ray films are very important because those can show the most of
      foreign bodies or indirect radiographic signs of a bronchial foreign body.
      Nowadays, bronchoscopy is the method of choice for removal foreign bodies from
      the tracheobronchial tree. If there are not complications, most of patients may
      recover and become non-symptomatic in a short-term after the foreign body
      extraction. We show the case of a nine years old boy who suffered the aspiration
      of a tack, which stayed in a bronchi during several years, and was misdiagnosed
      as asthmatic.

PMID- 12190006
TI  - [Reactive polyarthritis and painful dermatographism caused by Helicobacter
      pylori].
AB  - This paper describes a 36 year-old white woman with six month history of
      epigastric abdominal pain, reactive arthritis and painful dermographism. Serum
      antibodies to Helicobacter pylori were identified. All symptoms subsided when she
      received eradication treatment.

PMID- 12190007
TI  - [The pregnant patient with acute liver disease].
AB  - Acute liver disease was diagnosed in three pregnant patients: two 30-year-old
      women had a 'haemolysis, elevated liver enzymes, low platelets' (HELLP) syndrome
      and acute fatty liver of pregnancy, respectively, and a 20-year-old woman had
      acute liver failure due to acute hepatitis B. The first two patients had a
      caesarean section, the third one delivered her child, which died spontaneously
      shortly after birth at a gestational age of 23 weeks. She was then treated by
      liver transplantation. All three patients left the hospital in good condition.
      Liver diseases in pregnancy may be pregnancy-related, e.g. the HELLP syndrome and
      acute fatty liver of pregnancy, but they may also be coincidental phenomena, e.g.
      viral hepatitis. The HELLP syndrome is often associated with pre-eclampsia, and
      presents with epigastric pain and thrombocytopenia with haemolysis. Acute fatty
      liver disease and acute liver failure due to hepatitis present with liver
      insufficiency characterised by anorexia, nausea, coagulopathy, hypoglycaemia and
      elevated serum ammonia levels. Management depends on the diagnosis and the
      gestational age; pregnancy complicated by acute fatty liver disease should be
      terminated while pregnancy complicated by the HELLP syndrome early in pregnancy
      may be maintained to improve the outcome of the foetus. In acute liver failure
      due to viral hepatitis, termination of pregnancy alone does not affect the
      disease.

PMID- 12190008
TI  - [Thalidomide: new uses for an old drug].
AB  - Thalidomide was withdrawn from the market in the early sixties because of its
      teratogenic effects. Despite forty years of research, the mechanism of
      thalidomide embryopathy has remained unsolved. Thalidomide has various
      immunomodulatory effects. Thalidomide inhibits TNF alpha production, has T-cell
      costimulatory properties and modulates the expression of cell surface molecules
      on leukocytes in vivo. Thalidomide also has anti-angiogenic activity in vivo.
      Angiogenesis plays an important role in the pathogenesis of both solid tumours
      and hematologic malignancies such as multiple myeloma and lymphoma. In clinical
      studies, thalidomide has been used as an inhibitor of angiogenesis. Erythema
      nodosum leprosum is the only registered indication for the use of thalidomide in
      the United States of America. Thalidomide is also effective in the treatment of
      chronic graft-versus-host disease, mucocutaneous lesions in Behcet's syndrome and
      HIV infections, and multiple myeloma.

PMID- 12190009
TI  - [Short pregnancy interval and reproductive disorders].
AB  - The cause of the 'borderline personality disorder' of Vincent van Gogh has been
      discussed in social-psychiatric terms related to so-called 'substitute children',
      born after the loss of a previous child. A biological-organic genesis, i.e. the
      very short birth interval of precisely one year between Van Gogh and his older
      brother appears to be a more plausible explanation. Personality disorders, which
      are part of the spectrum of schizophrenic disorders, seem to belong to the very
      broad 'continuum of reproductive casualties' and to be caused by non-optimal
      maturation of the oocyte during the postpartum restoration of the ovulatory
      pattern. This continuum occurs during each of the transitional stages of
      reproductive life in which the maturation of the oocyte is constrained and
      consists of chromosomal aberrations, (discordant) monozygotic twins, early and
      late foetal death, preterm births, intrauterine growth retardation, congenital
      abnormalities, perinatal and neonatal mortality, cot death, growth and mental
      defects, and finally, chronic or 'constitutional' diseases. Non-optimal
      maturation of the oocyte appears to be a risk factor for the reproductive
      casualties stated.

PMID- 12190010
TI  - [Diagnostic image (99). An infant with feeding problems].
AB  - A 2-month-old, prematurely-born boy suffered from vomiting and failure to thrive
      due to the combination of a large hiatal hernia and malrotation of the intestine.

PMID- 12190011
TI  - [Thalidomide in the treatment of refractory multiple myeloma: a Dutch study of 72
      patients: an antitumor effect in 45%].
AB  - OBJECTIVE: To determine the efficacy and side effects of thalidomide in the
      treatment of refractory multiple myeloma. DESIGN: Retrospective, descriptive.
      METHOD: Data were obtained by means of case research on patients with refractory
      multiple myeloma who were treated with thalidomide at four regional hematological
      centres in the period from 1 May 1999 to 31 May 2001. The patients had previously
      been treated with one, two or three schedules of chemotherapy. The starting dose
      of thalidomide was 200 mg per day and the dose was increased gradually to a
      maximum of 800 mg per day depending on the tolerance. RESULTS: The 72 patients
      included 43 men and 29 women with an average age of 62 years (range: 38-82
      years). The median follow-up was 13 months (range: 2-25). Thalidomide as a single
      agent was prescribed for 64 patients, of whom 29 (45%) responded; a complete
      response was achieved in 3 patients, a partial response in 18, and a minor
      response in 8. In 4 of 11 patients with an extramedullary plasmacytoma a decrease
      in size was observed. The median duration of the response was 9 months (range:
      from 2 till > 24). The median overall survival from the start of thalidomide
      treatment was 9 months. Thalidomide plus dexamethasone was given to 9 patients
      who did not respond to thalidomide alone, and in 6 of them a reduction of M
      protein was then observed. The most frequent adverse effects were constipation,
      drowsiness, somnolence, dizziness, venous thrombosis and polyneuropathy. Doses of
      up to 400 mg per day were generally well tolerated. CONCLUSION: Thalidomide has
      antitumour activity in refractory multiple myeloma.

PMID- 12190012
TI  - [Microvillus inclusion disease, a rare cause of severe congenital diarrhea].
AB  - To date, microvillus inclusion disease (MID) has been diagnosed in six Dutch
      patients. It is a rare autosomal recessive hereditary intestinal disorder mostly
      presenting with malabsorption and severe secretory diarrhoea from birth. The
      diagnosis is confirmed by electron microscopy of intestinal mucosal biopsies,
      which show characteristic intracytoplasmic vesicles containing clearly
      recognisable microvilli and irregularly distributed microvilli in the brush
      border. The two clinical forms of the disease that have been recognised
      internationally, a 'congenital' and a 'late-onset' form of MID, have also been
      observed in the Dutch patients. At the last follow-up five patients had died, the
      sixth was 17 years old and alive. The pathogenesis and genetics of MID are, as
      yet, unknown. Eventually, all patients die from complications of the disease,
      notably from the total parenteral nutrition. The only chance of survival is
      intestinal or combined liver-intestinal transplantation.

PMID- 12190013
TI  - [Hypocalcemic delirium due to magnesium sulphate therapy in a pregnant woman with
      pre-eclampsia].
AB  - A 34-year-old pregnant patient, admitted with severe pre-eclampsia and the
      'haemolysis, elevated liver enzymes, low platelets' (HELLP) syndrome at 31 weeks
      gestational age, was treated with magnesium sulphate for imminent eclampsia. The
      further management was aimed at prolonging gestation. During treatment, a
      delirium developed with myoclonus. As the foetal condition deteriorated,
      caesarean section was performed. Afterwards, the delirium proved to have been due
      to hypocalcaemia. After appropriate treatment the patient recovered. In pre
      eclampsia, the calcium metabolism is disturbed. Hypermagnesaemia inhibits
      parathyroid hormone secretion and can therefore cause hypocalcaemia. In rare
      cases, this may cause a delirium, which is unusual in pre-eclampsia. If the
      clinical (neurological) picture in a pregnant woman with severe pre-eclampsia,
      who is receiving treatment with magnesium sulphate, is not fully understood,
      hypocalcaemia should be considered.

PMID- 12190014
TI  - [One hundred years of the Association of Surgeons in the Netherlands. VIII.
      Surgical oncology].
AB  - The Dutch surgical oncologists founded the Dutch Society for Surgical Oncology in
      1981 with the aim of providing the best possible level of expertise in the
      multidisciplinary approach to the treatment of cancer, which at that time was a
      new development in cancer care. Since then, many developments have contributed to
      improving the outcome of care for the patient suffering from malignant disease.
      Surgeons have often played an initiating and pivotal role in these developments.
      Furthermore, in recent years there has been a strong development in quality
      awareness. This has led to a greater degree of cooperation in which intensive
      contacts exist. At the same time developments have taken place in surgical
      oncology: the care provided has developed from a broadly based care of the
      patient with a malignancy to care system concentrating on organ systems. As a
      result of this, the multidisciplinary therapeutic approach to the patient with
      cancer has been further developed. This might however lead to a fragmentation of
      oncological care and a loss of identity for the surgical oncologist, who possibly
      more than any other sub-specialist plays a pivotal role in caring for the patient
      with a solid malignancy.

PMID- 12190015
TI  - [Prenatal diagnosis for hereditary predisposition to mammary and ovarian
      carcinoma--defining a position].
AB  - Prenatal testing for a BRCA mutation, the hereditary trait for mammary and
      ovarian carcinoma, with the intention of selective termination of pregnancy in
      case of a female carrier is a controversial ethical issue. Based on a review of
      the (limited) medical literature as well as of Dutch policy statements relating
      to this subject, the following conclusions and recommendations are proposed: (a)
      the decision to opt for prenatal BRCA testing and selective termination of
      pregnancy in case of a BRCA mutation in the foetus cannot immediately be judged
      unacceptable from an ethical point of view; (b) prenatal BRCA testing is morally
      defensible only in case of a female foetus and if the parents at least have the
      intention to terminate the pregnancy if the foetus is a carrier, although the
      final decision is in any case up to the parents only; (c) prental testing for a
      BRCA mutation should only be done after extensive counselling of the parents,
      during which not only the medical genetic aspects but also the ethical aspects of
      prenatal BRCA testing are discussed.

PMID- 12190016
TI  - [Patient compliance in HIV infection: independent of nationality but worse in
      heterosexual infected patients, intravenous drug abusers, blacks and Latin
      American patients].

PMID- 12190017
TI  - [Dissemination of hereditary diseases via donor sperm: no reason for reduction of
      possible number of offspring per donor in the Netherlands].

PMID- 12190018
TI  - [The last breath. The decision of whether or not to ventilate patients with
      severe chronic obstructive pulmonary disease].

PMID- 12190019
TI  - [The study of bacterial glycopolymers using laser spectroscopy].
AB  - A possibility has been demonstrated to use laser spectroscopy of bacterial
      glycopolymers by means of measurement of their water solutions fluorescence.
      Comparative investigations of native lipopolysaccharide (LPS) Ralstonia
      solanacearum and its structure components permits a supposition to be made that
      the LPS total spectrum is a result of superposition of the spectrum of O-specific
      polysaccharide and core oligosaccharide as well as core oligosaccharide and lipid
      A. The LPS spectrum maximum shift is determined by core oligosaccharide and lipid
      A luminescence contribution. A decrease as well as complete loss of serological
      activity as a result of 30 and 60 min UV irradiation of LPS has been established.
      It has been shown that LPS Rhizobium leguminosarum bv. viciae quenches
      luminescence of host-plant (pea) lectin depending on the extent of their
      affinity. Luminescence spectrum of glucan Sinorhizobium meliloti CXM1-188 and two
      its LPS-mutants differ between themselves both in luminescence intensity and in
      presence and expression degree of the site 2 with maximum 2.8 eV.

PMID- 12190020
TI  - [Searching for restriction endonucleases, finding out the heterogeneity of the
      16S rRNA in some species of lactic acid bacteria].
AB  - The preliminary test of carbohydrates fermentation has been carried out to
      confirm a regular position for some lactic acid bacteria strains. Restriction
      cards have been compiled for Lactobacillus plantarum, L. delbrueckii and
      Streptococcus salivarius using Vector NTI program. A comparative analysis of the
      restriction cards has shown presence of unique sites of restriction
      endonucleases, which can be used for differentiation of the above-stated species.

PMID- 12190021
TI  - [Growth of phototrophic bacterium Rhodobacter sphaeroides and formation of
      carotenoids on mineral water "Dzhermuk"].
AB  - A possibility to use thermal carbon sulphate-hydrocarbonate mineral waters
      "Dzhermuk" as the basis of nutrient medium for growing has been established. No
      distinct correlation was observed between biomass accumulation and carotenoids
      formation: maximum yields of the biomass is registered under microaetrophilic
      growth conditions, while that of carotenoids--under anaerobic conditions. Maximum
      synthesis of carotenoids is observed at illumination of 1000-1500 lx, more
      intensive illumination (3000 lx) results in the decrease of their synthesis.
      Spheroiden, which makes up about 40-45% of the total amount of carotenoids, is
      predominant. The biomass drying and storage period (2 yr.) affect inconsiderably
      the quantitative composition of pigments.

PMID- 12190022
TI  - [Characterization of marine bacteria Pseudoalteromonas citrea degradating
      fucoidan].
AB  - Two strains KMM 3296 and KMM 3298, isolated from the surface of brown algae
      Chorda filum and Fucus evanescens thalli and strain KMM 3297, isolated from
      celomic fluid of holoturian Apostichopus japonicus, were identified as
      Pseudoalteromonas citrea on the basis of pheno-, geno- and phylotypic features.
      The studied bacteria were different from other bacteria of the species as to
      their ability to destruct sulphated polysaccharides of brown algae, fucoidans.

PMID- 12190023
TI  - [Some peculiarities of DNA structure of cyanophage LPP-3].
AB  - The efficiency of radioactive labeling of 3'- and 5'-ends of cyanophage LPP-3 DNA
      by polynucleotide kinase T4 and terminal transferase under various reaction
      conditions has been investigated. The obtained data prove that cyanophage LPP-3
      DNA has the protruding 3'-ends. The experiments on ligation of native molecules
      of LPP-3 DNA evidence that the virus genome ends do not display any
      complimentarity. Separate fragments of LPP-3 DNA were cloned. The restriction
      analysis of the cloned fragments has confirmed a supposition on the absence of
      LPP-3 cyanophage of GGGCC and GGCCC sequences in the genome. A hypothesis has
      been suggested about similar site-specificity of the virus. Counterselection of
      the genome LPP-3 cyanophage allows it to be considered a promising one in the
      construction of new cloning vectors in cyanobacterium.

PMID- 12190024
TI  - [Influence of composition of the nutrient medium on growth and development of
      entomopathogenic bacteria Bacillus thuringiensis].
AB  - New medium for cultivation of Bacillus thuringiensis has been elaborated with the
      help of a simplex method for mathematical planning the experiment. The optimized
      medium containing green syrup, corn extract, sodium humate and mineral salts,
      allowed to increase the biomass titer by 45%, endotoxin by 220% as compared to
      the initial medium. Insecticide activity of Bacillus thuringiensis culture grown
      on the new culture medium exceeds considerably that on the initial culture
      medium.

PMID- 12190025
TI  - [Comparative estimation of biocides and crown-ethers effect on micromycete
      destructors cultures].
AB  - Influence of catamine AB, catapine, macrocyclic polyethers (crown-ethers [15]C-5,
      B[15]C-5, [18]C-6, B[18]C-6, DCH[18]C-6, DA[18]C-6) and mixtures of catapine with
      crown-ethers on fungal test-cultures of Aspergillus sydowii (Bain. et Sart.) Thom
      et Church, Cladosporium cladosporioides (Fr.) de Vries and Penicillium tardum
      Thom. It is shown, that solutions of catamine AB show the inhibiting effect in
      concentrations which are one level lower than in catapine. Inhibition influence
      on the growth of fungal test-cultures is found to be higher for crown-ethers
      B[15]C-5 and B[18]C-6 in contrast to [15]C-5 and [18]C-6 (B[15]C-5 > [15]C-5;
      B[18]C-6 > [18]C-6). Synergism of inhibition influence of catapine-bactericide
      and crown-ethers in the mixture on fungal cultures is established in contrast to
      influence of separate components of the mentioned substances.

PMID- 12190026
TI  - [Correlation between Staphylococcus carriage, specific antibody-production and
      AB0-blood grouping in plasma donors].
AB  - Interaction peculiarities of three components of the immune human homeostasis
      antigens of blood groups AB0, staphylococcus antigens and antistaphylococcus
      antibodies have been investigated. Donors (85) of antistaphylococcus plasma
      immunized by staphylococcus anatoxin have been investigated. It is found that the
      nasal staphylococcus carriage in donors depends on the level of specific and
      natural antibodies and on the coincidence between the staphylococcus antigen
      structure and the protein substance of the specific blood group factors.

PMID- 12190027
TI  - [Comparative study of properties of temperate erwiniophages 49 and 59].
AB  - Molecular-biological properties of two relative temperate erwiniophages 49 and 59
      have been comparatively studied. The both phages are highly specific with respect
      to sensitive bacteria and lyse only inconsiderable quantity of amylovora-like
      strains of Erwinia horticola. It has been established that erwiniophages are
      distinguished by the basic parameters of a single reproduction cycle in the cells
      of common host E. horticola 450. Considerable differences between phages have
      been also found in the areas of genomes responsible for the establishment and
      maintenance of lysogenic state in the cells of the bacterium-host. Study of
      structure polypeptides has confirmed the identity of capsids and tails of phages
      49 and 59. It has been shown that phage 49 has another, as compared to phage 59,
      basal plate, which availability destabilises the phage tail and leads to virion
      destruction under various physical effects. Virion DNA of phages 49 and 59 are of
      the same size--47.9 kbp, but differ as to GC-content. Using the restriction
      analysis it has been shown that genome of phage 49, as well as the genome of
      phage 59, is permuted, but its permutation is of discrete character. The fact of
      recombination interaction between erwiniophages 49 and 59 has been established.
      It is supposed that phage 49 is the recombination (hybrid) derivative of phage 59
      and unknown phage, or prophage, genetic module. The given recombination,
      probably, took place under the persistence of different phages in the general
      polylysogenic system of E. horticola.

PMID- 12190028
TI  - [Fructose-bisphosphatase of microorganisms].
AB  - Data from modern scientific literature concerning general characteristics of
      fructose-bisphosphatase--the key enzyme of microorganisms gluconeogenesis pathway
      have been analyzed in the survey. The conditions of fructose-bisphosphatase
      functioning in the cell--activation and repression, have been described.
      Regulation of prokaryotes enzyme activity by fructose-1.6-bisphosphate, fructose
      2.6-bisphosphate, phosphoenol pyruvate, metal cation, etc., is discussed.
      Absolute dependence of fructose-bisphosphatase activity on cations of bivalent
      metals (Mg2+, Mn2+) and AMP is shown. Special attention was given to the
      functioning and characteristics of the enzyme in prokaryotes and eukaryotes:
      their similarity and differences. Data about the basic enzyme of gluconeogenesis
      pathway in Gram-positive and Gram-negative microorganisms, conditions of its
      functioning in autotrophs and heterotrophs have been generalized for the first
      time. Genetical and molecular biological properties of fructose-bisphosphatase in
      microorganisms have been considered. At the same time, the fact is established
      that the above enzyme has not been investigated in numerous microorganisms.

PMID- 12190029
TI  - [Search for lectin producers among the yeast of Pichia Hansen emend. Kurtzman
      genus].
AB  - Strains (103) of yeast from Pichia genus: P. anomala, P. guilliermondii and P.
      membranaefaciens species have been investigated. The researchers have found 87
      strains (84.5%) capable to form extracellular and surface lectins with activity
      to 512 hemagglutinating units. The overwhelming number of strains (75.7-92.6%)
      synthesized lectins of the both forms. Considerably less quantity of lectin
      producers of some form--extracellular or surface ones--have been found.
      Availability of producers of extracellular lectins was characteristic to greater
      extent of the yeast of P. anomala and P. guilliermondii, and producers of surface
      lectins--mainly of P. guilliermondii. The most active producers of lectins have
      been isolated from human and animal organisms, soils and wine.

PMID- 12190030
TI  - [Method for studying horizontal transfer of plasmids in Erwinia carotovora].
AB  - A simple method to determine frequency characteristics of the horizontal transfer
      of antibiotic resistance by transconjugative plasmids of various incompatibility
      groups into Erwinia carotovora strains has been developed. The proposed method
      for selection of E. carotovora transconjugates provides for the use of selective
      medium with pectin and corresponding antibiotic, which permits carrying out
      reliable counterselection of the donor (Escherichia, Salmonella). The proposed
      method helped to study horizontal transfer of plasmids RP4 (Inc P), R 391 (Inc J)
      and pKM101 (Inc N) to some E. carotovora strains and to demonstrate their
      inheritance as extrachromosomal DNA in Erwinia cells.

PMID- 12190031
TI  - [Detection and identification of the transgenes in genetically modified plants on
      the example of Bt-potato].
AB  - We have developed diagnostic system for revealing 35S promoter CaMV and transgene
      CryIIIA in transgenic potato NL Russet Burbank and NL Superior companies
      Monsanto. Using the data about nucleotide sequences of 35S promoter (AF234316
      GenBank) and gene CryIIIA (X70979 GenBank) oligonucleotides primers were
      synthesized for polymerase chain reaction (PCR). The technique of genomic DNA
      isolation from plant material, suitable for PCR has been optimized. Using
      Touchdown PCR method presence of specific transgene in a Bt-potato was shown.
      This method can be used in routine laboratory practice for revealing 35S promoter
      in genetically modified plants and for identification of specific transgene
      CryIIIA in the transformed Bt-plants.

PMID- 12190032
TI  - [Comparative analysis of radial linear growth velocity of micromycetes isolated
      from different ecotopes].
AB  - The work aim was the discovering of peculiarities of microscopic fungi responding
      to radioactive pollution by growth velocity change. The linear growth velocity of
      a broad range of micromycetes was analyzed. They were chosen in such a way that
      every species, as far as possible, was presented by the strains isolated from
      radioactive polluted and clean regions. Most of the studied species were
      characterized by the absence of reliable growth velocity differences of strains
      of the same species growing on rich and starving media. Only two species-
      Aureobasidium pullulans and Penicillium spinulosum were the exception. Their
      growth velocities on malt-agar were much more then those on starving medium (1.7
      3.6. times). Species Hormonema dematioides did not have reliable differences of
      growth velocity on optimal and starving media, but A. pullulans had this
      difference (2.3-3.6 times). It is supposed to use this observation to simplify
      identification of these species. Only strains within species Cladosporium
      sphaerospermum and especially P. funiculosum isolated from radioactive polluted
      ecotopes had growth velocity which was less then that of the strains from clean
      regions. The delay of growth velocity in such conditions can testify to adaptive
      change of metabolic processes of these strains. The strains which were
      characterized by delay of growth velocity existed at the substrates with high
      radioactive pollution for a long time.

PMID- 12190033
TI  - [Distribution of soybean mosaic virus antigen in the leaves of soybean plants
      with different reaction to virus infection].
AB  - The distribution and accumulation of soybean mosaic virus antigen in the leaves
      of sensitive plants with well expressed mosaic symptoms and symptomless tolerant
      soybean plants Glycine max (L.) Merr. were similar. Low concentration of virus
      antigen was found in extremely resistant soybean plants in mechanically
      inoculated leaves and those of the 2-4 circles two-three weeks after inoculation
      but 5 weeks later the virus antigen was detected only in the top leaves.

PMID- 12190034
TI  - [Antibiotic properties of the Pseudoalteromonas genus bacteria isolated from the
      Black Sea water and molluscs].
AB  - Antagonistic properties of 41 strains of Alteromonas-like bacteria isolated from
      the Black Sea water and molluscs have been studied. Being grown on the rich
      medium "B" for marine bacteria, 21% of strains have shown high antagonistic
      activity against phytopathogenic fungi; 6% of strains inhibited the growth of
      Bacillus subtilis, Proteus vulgaris and Candida albicans. Spectrum of
      antagonistic activity was essentially changed on synthetic "BM" medium with
      acetate, glutamate, alpha-alanine as a single source of carbon and was directed
      against Pseudomonas aeruginosa. Culture liquids and acetone extracts of microbial
      biomass of 34% of the studied strains have shown activity against bacteria, fungi
      and cyanobacteria. Strains producing the wide spectrum of antimicrobial
      substances (Alteromonas macleodii, Pseudoalteromonas citrea, P. haloplanktis, P.
      aurantia, Pseudoalteromonas sp.), fungicidal and algocidal substances have been
      found. Both extra- and intracellular metabolities of marine bacteria (including
      the pigments) were active.

PMID- 12190035
TI  - [Species and strain sensitivity of diasotrophs to heavy metals].
AB  - The species and strain sensitivity of free and symbiotic nitrogen-fixing agents
      to heavy metals: cadmium, copper, lead and zinc in the gradient of concentration
      from 0.5 to 20.0 MPC/l has been studied under the laboratory conditions.
      Azotobacter (35 strains) and rhizobia (63 strains) have been tested. It has been
      established that zinc and copper are more toxical for free nitrogen-fixing agents
      than lead and cadmium. Among symbiotrophic nitrogen-fixing agents the nodule
      bacteria for alfalfa were most sensitive to cadmium; nodule bacteria of pea and
      lupine--to copper; those of galega and soya--to zinc. Lead proved to be the least
      toxic for rhizobia. Negative effect of the heavy-metal mix on diasotrophs was
      higher than that of each separate metal. The cultures resistant to the effect of
      heavy metals have been found which may be used when producing preparation for
      biological reclamation of polluted soils.

PMID- 12190036
TI  - [Spreading of fungi of Fusarium Lk : Fr. genus in the soil of mountain-forest
      reservation of Chatkala].
AB  - The species composition of Fusarium genus is more rich and diverse in
      agrophytocenoses than in natural soils of vertical zones of the Chatkala mountain
      systems. Soils at the height of 600-700 m were the poorest in the number of
      Fusarium genus fungi while agrophytocenoses were the richest in the fungi.
      Certain differences in the species diversity and the number of Fusarium genus
      were found in the soil of the root zone of plants Poa bulbosa, Juniperus
      sarevschanica and Festuca valesiaca. The maximum of their development was
      observed in the alpine soils in summer and in autumn and in alpine soils in
      spring and in summer. The possibilities of plants affection increase in the
      period of biological activity of these fungi. Representatives of Fusarium genus
      are an important component of phyto and agrophytocenoses; they take active part
      in the processes of soil formation.

PMID- 12190037
TI  - [Modeling of dynamics of microorganisms quantity in the soil polluted by heavy
      metals].
AB  - Microflora of soils polluted by heavy metals was the subject of monitoring
      investigations. Basing on the experimental data obtained with the use of
      interactive system ASTRID by the method of group accounting of arguments,
      mathematical models were constructed which describe the dynamics of
      microorganisms quantity, depending on the number of ecological factors and
      presence of heavy metals in the soil. The models allow one to predict the number
      of microorganisms in the soil under certain parameters of the environment, to
      determine "critical" deviations from the predicted values as well as to renew the
      intermediate data for obtaining uniform series of ecological researches.
      Prospects of the use of the inductive approach for modeling of microbiological
      processes in the soil have been demonstrated.

PMID- 12190038
TI  - [Effect of gas mixture component composition on the process of hard materials
      colonization by methanotrophic bacteria].
AB  - A device has been proposed which allows decreasing a possibility to contaminate
      the inoculum of methane-using bacteria (methanotrophs) under its growing. The gas
      mixture composition has been investigated for the intensity of grass and
      polysterene colonization by two species of methanotrophs: Methylococcus
      capsulatus UCM B-3030, possessing hydrophilic surface and hydrophobic
      Methylocystis parvus UKM B-3490T. It has been shown that immobilized
      methanotrophic bacteria can colonize the above materials in the wide range of
      methane and oxygen concentrations in gas mixture. The process of hard materials
      colonization was most intensive when the mixture contained 17-28% of methane and
      5-28% of oxygen. No essential differences have been registered under colonization
      of hydrophilic (glass) and hydrophobic (polysterene) materials by the both
      cultures.

PMID- 12190039
TI  - [Immunosuppressive components of extracellular lipopolysaccharide highly virulent
      strain Salmonella typhimurium 1468].
AB  - Immunosuppressive activity of culture liquid substrate (CFS) of highly virulent
      strain Salmonella typhimurium has been studied. A model of delayed
      hypersensitivity (DHS) to nonbacterial antigen in mice, a method of gel
      filtration through the sephadex column G-200, immunosorbents were used. Three
      components with immunosuppressive activity: thermolabile component and
      thermostable one with direct immunosuppressive action and the third thermolabile
      component which manifested inductive immunosuppressive activity only after redox
      treatment have been revealed in the strain CFS. O-specific and lipid parts were
      found in the composition of all the components. This allowed them to be related
      to lipopolysaccharide.

PMID- 12190040
TI  - [Strategy of obtaining microbial exopolysaccharides possessing stable preset
      properties].
AB  - Basing on the development of approaches to the controlled regulation of synthesis
      of the complex polysaccharide preparation ethapolan (producer Acinetobacter sp.)
      the strategy of obtaining microbial exopolysaccharides (EPS) with stable
      composition and properties was determined. The strategy is based on the following
      principles of regulation of composition, physico-chemical properties and
      synthesis intensification of EPS: 1) to find out EPS functional groups
      determining their physico-chemical properties and factor providing synthesis of
      EPS with certain functional groups; 2) to study changes of EPS composition and
      properties during producer cultivation and to determine growth phase in which the
      synthesis of EPS possessing necessary properties occurs; 3) to investigate
      interrelation between EPS physico-chemical properties and their protective
      functions and to determine cultivation conditions necessary for development of
      EPS protective functions; 4) analysis of metabolic pathways of EPS synthesis,
      elucidation of "bottlenecks" in producer's metabolism and search for ways toward
      their elimination.

PMID- 12190041
TI  - The effect of gamma-linolenic acid on plasma and membrane lipids and renal
      prostaglandin synthesis in older subjects.
AB  - Senescence is associated with a decreased activity of enzyme delta-6 desaturase,
      which converts linoleic acid to gamma-linolenic acid. This enzymatic defect may
      alter the composition of plasma and membrane lipids, and influences the
      biosynthesis of renal prostaglandins. Exogenous supplementation of GLA during 3
      months increases the plasma level of dihomo-gamma-linolenic acid (p < 0.002), and
      to a smaller degree, the level in erythrocyte membrane lipids. This treatment was
      associated with a beneficial reduction of cardiovascular risk factors (arterial
      hypertension, total cholesterol, apolipoprotein B, HDL-cholesterol,
      apolipoprotein A-I) and the renal function has become stable reached. Epogam
      treatment also increased the biosynthesis of renal prostaglandins, especially
      that of prostaglandin E2, which has a vasodilatory effect on vessel walls and
      reduces the elevated blood pressure. CONCLUSION: Dietary supplementation of
      essential fatty acids such as gamma-linolenic acid to old subjects has beneficial
      effect on their health condition. (Tab. 6, Fig. 5, Ref. 37.)

PMID- 12190042
TI  - Carcinoid tumors--somatostatine in the diagnosis and therapy.
AB  - BACKGROUND: Carcinoid tumors have a neuroendocrine origin and endocrine activity
      is typical for them. OBJECTIVES: The main objective of the present study was to
      determine differences in the levels of an endogenous somatostatin, a neuron
      specific enolase in serum and excretion of 5-HIAA in the urine in patients with
      carcinoid tumors and also to determine the changes of these parameters during the
      treatment with long acting somatostatin analogue--lanreotide. SUBJECTS AND
      METHODS: 30 pts with carcinoid tumors (20 pts with metastatic disease, 10 pts
      after resection of the primary tumor without known metastases at the time of the
      investigation) and 12 healthy probands were included in the study. Circadian
      rhythm of endogenous somatostatin in all groups was performed. Levels of neuron
      specific enolase in the serum and the excretion of 5-HIAA in the urine in pts
      with carcinoid tumors were done. The estimation of these parameters were repeated
      in the group of pts with advanced metastatic disease during the treatment with
      the lanreotide. RESULTS: We confirmed the existence of the circadian rhythm of
      endogenous somatostatin in all groups. Chronogram of somatostatin in pts without
      known metastases shows the same characteristics as the chronogram of healthy
      volunteers. The chronogram of pts with metastatic carcinoid disease shows a
      statistically significant differences in comparison with healthy volunteers-
      higher mesor and later acrophase of 24-hour rhythm (p < 0.05). During the therapy
      with lanreotide lower mesor was observed (p < 0.05). The amount of the 5
      hydroxyindolacetate acid in urine in pts with metastatic carcinoid was
      statistically significant higher than in the pts without metastases (p < 0.001).
      During therapy with the lanreotide the decrease in the 5-HIAA in the urine (p <
      0.05) was observed. Neuron specific enolase in the serum was higher in group with
      the metastatic disease (p < 0.001). CONCLUSION: Abnormalities in the somatostatin
      secretion and the concentration of the neuron specific enolase in serum are
      useful markers for the differential diagnosis and might distinguish the carcinoid
      patients with and without metastases. Urine excretion of 5-HIAA is a good marker
      of endocrine activity of the carcinoid tumor. (Fig. 4, Tab. 3, Ref. 22.)

PMID- 12190043
TI  - Immune thrombocytopenic purpura in children.
AB  - Immune thrombocytopenic purpura (ITP) is the most commonly acquired bleeding
      illness in children. 70-80% of children resolve from acute state within few weeks
      and months with a complete retrospective changes in recovery of reference values.
      The aim of this work was to evaluate a group of patients with diagnosis of ITP
      treated or followed from 1979 to 1999. There were found no differences in
      achieving the remission in the acute phase of ITP (this means till the 6th month
      from the first documented thrombocytopenia) according to retrospective analysis
      and comparison of three groups of children in whom the diagnosis of ITP was made
      from 1979 to 1991 (group A), from 1992 to 1994 (group B) and from 1995 to 1999
      (group C). The groups differed in their therapeutic strategies in various time
      periods as to the time of the diagnosis. In group A, 75% of patients were treated
      with oral corticosteroids (prednisone). In group B, 10.8% of patients were
      treated with i.v. application of corticosteroids and 43.3% had no therapy in the
      acute phase. In group C, 28% of patients were treated with i.v. application of
      corticosteroids and 36.6% of patients had no therapy applied. A comparable degree
      of remission in the acute phase with 48%, 54%, or 50% of children with reference
      values of platelets at the time of six months from the beginning of the disease
      were achieved. In the group A, the remission was achieved in 85% of children at
      the end of the 5th year of the follow-up, in the group B in 75% of children to
      the latest control of platelets in our outcome clinic for children and follow up
      in the group C in 68% of children the remission was achieved after one year.
      (Tab. 4, Fig. 2, Ref. 10.)

PMID- 12190044
TI  - Heterotopic pancreas in gastric antrum with macroscopic appearance of gastric
      polyp.
AB  - Heterotopic pancreas is a relatively rare clinical diagnosis, not commonly
      involved in differential diagnostic considerations of GI symptoms. The authors
      report a case of heterotopic pancreas discovered endoscopically in the gastric
      antrum. A 60-year-old woman presented with epigastric pain. The patient took
      alendronate for osteoporosis. The endoscopic examination revealed Helicobacter
      pylori positive antral atrophic gastropathy and a well delineated hemispherical
      polyp, 8 mm in diameter, in the antrum of the stomach. Histology showed antral
      gastritis and the presence of heterotopic pancreas. After dietary measures and
      Helicobacter eradication, the patient was relieved of symptoms. According to the
      authors' opinion, the finding of heterotopic pancreas did not necessitate
      intervention, and was an incidental finding. The authors discuss the significance
      of heterotopic pancreas with the conclusion that the resection of the lesion is
      indicated only if consistent symptoms are present. Fig. 3, Ref. 28.)

PMID- 12190045
TI  - Genetically modified animals and human medicine.
AB  - Development of the methods of molecular and cellular biology now allows specific
      genetic manipulations of laboratory animals leading to the introduction of an
      exogenous gene to their genome or elimination of a particular endogenous gene.
      This approach represents an invaluable biological tool for a better understanding
      of basic physiological and pathological processes. In all fields of biomedical
      research, transgenic and knockout animals have contributed greatly to
      understanding the molecular cause of several human diseases and allowed
      production of their animal models, which represent a useful tool for development
      of new medical drugs and therapeutic procedures for the treatment of human
      diseases. The aim of this short review is to provide a brief survey of the
      production of genetically modified animal and to discus their importance human
      medicine. Fig. 2, Ref. 19.)

PMID- 12190046
TI  - Immunosuppressive treatment of Crohn's disease with fistulae.
AB  - The rise of fistulae in Crohn's disease has been classed with the disorder
      complications, although it is a possible component of natural development of the
      so-called A type (De Dombal classification) or aggressive-perforating type
      (Greenstein's classification) of this idiopathic intestinal inflammation.
      Fistulae are accompanying colic localization of Crohn's disease in 20%, ileocolic
      affection in 40%, where 35% of them are perianal fistulae, and about 34% entero
      enteral or entero-cutaneous ones. Other complications (urogenital tract, biliary
      tract) are mentioned infrequently in literature. Besides surgical approaches in
      the therapy, dominant post in the conservative area is taken up by an antitumor
      necrotizing factor, antibiotics and immunosuppressives whose position is,
      however, the most problematic although the literature references about the
      effectiveness of azathioprine, 6-mercaptopurine, cyclosporine, tacrolime and
      methotrexate have had nearly 25-years tradition. The authors present their own
      experience with applying a combination of cyclosporine, azathioprine in the
      treatment of perianal fistulae in a set of 21 patients from the period of 1995
      2000. In their opinion, the therapy success is limited especially by early
      starting the treatment (11 cases of effective therapy) and choosing a resolute
      method that is, according to them, sequential immunosuppression. (Tab. 2, Ref.
      32.)

PMID- 12190047
TI  - Pharmacoeconomic analysis of conservatively treated patients with nephropathies
      in western Slovakia regions.
AB  - The prevalence of patients with chronic nephropathies leading to the end stage of
      renal failure (ESRF) is increased. The conservative therapy of patients in the
      phase of ESRF as well as the performance of hemodialysis represent an extensive
      burden on health care budgets. AIM: The aim of the study was to evaluate the
      financial expenses for medications in group of conservatively treated patients
      with nephropathies. PATIENTS AND METHOD: One hundred and two patients (56
      females, 46 males) aged 21-84 years with nephropathies collected from three out
      patient departments of nephrology in the regions of Bratislava and Nitra (Western
      Slovakia) were enrolled into the study. RESULTS: The total financial expenses
      represented 2,889,778 Sk The average expense per 1 patient/1 year was 28,331 Sk
      and that of 1 patient/1 day was 77.6 Sk, respectively. Antihypertensive therapy
      represented 1st position (29.4%) of the total financial cost followed by keto
      analogs (27.5%), hypolipideamics (14.8%), drugs for disorders of calcium
      metabolism (14.4%) and antianaemics (6.2%), respectively. The group of "other"
      drugs represented 7.7% of total costs. CONCLUSIONS: Results show that the
      financial expenses for pharmacotherapy in conservatively treated patients with
      nephropathies are high, but significantly less expensive in comparison with
      hemodialysis (700,000-1,000,000 Sk/year/patient). The prevention and the slowing
      down of the progression of renal disease seem to be crucial in the management of
      nephropathies. The therapeutic approach in conservatively treated patients with
      renal diseases was rational and up to date. (Tab. 1 Fig. 5, Ref. 12. )

PMID- 12190048
TI  - Changes of decartograms under gravitational acceleration and microgravity.
AB  - The Decarto technique was used to study the orthogonal ECGs recorded in 23
      subjects during parabolic flights (44 records). A parameter of the instantaneous
      decartograms, namely the activation area (AA), which is the total area of the
      depolarization front projection on the image sphere, was analyzed. We compared
      the values of AA during the periods of horizontal flight, upward parts of all
      parabolas, and the initial 10 s of microgravity of all parabolas. According to
      the characteristics of the vectorcardiograms and AA, all subjects were subdivided
      into 3 groups: with increased electric activity of the right ventricle (I), the
      left ventricle (II) and both ventricles (III). Changes of AA with change of
      gravitational levels in these groups showed some differences. In groups I and II,
      the AA of the initial part of the QRS complex increased during microgravity and
      decreased during hypergravity. In group III it decreased during microgravity and
      changed variously during hypergravity. The AA of the middle part of the QRS
      complex decreased during microgravity and increased during hypergravity, and
      these changes were more pronounced in group III. The changes of AA in groups I
      and II may be explained by the Brody effect. In group III, AA seems to be
      influenced by some additional factors, possibly by changes in the intramyocardial
      or intraventricular blood volume. The AA of the last part of the QRS complex
      increased during microgravity and decreased during hypergravity in all groups.
      This may be explained by an effect of mutual neutralization of depolarization
      fronts related to the changes of the QRS duration.(Fig. 3, Ref. 4)

PMID- 12190049
TI  - State, JCAHO find low staffing at Md. hospital.

PMID- 12190050
TI  - [Human prion diseases].
AB  - Prion diseases are rare neurodegenerative transmissible fatal diseases affecting
      humans and mammals. The causative agent is a novel pathogen termed the prion.
      Unlike classical infectious agents such as bacteria or viruses, prions lack an
      independent genome and consist largely of an abnormal form of the host-encoded
      prion protein. Creutzfeldt-Jakob disease (CJD) is the main representative of
      human prion diseases that may be sporadic in most cases, hereditary, or acquired.
      Clinical examination yields only a suspected diagnosis with formal criteria for
      probable or possible. Definite diagnosis relies on autopsy and neuropathology
      findings. This is also true for the new variant CJD (vCJD), a previously unknown
      prion disease of humans that is connected with the same strain of prions as found
      in bovine spongiform encephalopathy (BSE). The autopsy and handling of laboratory
      material for histopathological examination requires specific precautionary
      measures and decontamination. For definite histopathological diagnosis of a human
      prion disease, immunohistochemical detection of the prion protein deposits is the
      gold standard. Furthermore, molecular and genetic investigations are necessary
      for classification because a close correlation could be established between
      distinct CJD phenotypes, codon 129 genotypes of the prion protein gene, and the
      prion protein type.

PMID- 12190052
TI  - [Health and social insurance in Nordic countries].
AB  - BACKGROUND: There is no previous comparative review available of Nordic social
      insurance schemes for sickness benefits, rehabilitation allowance and disability
      pensions. METHODS: Based on existing publications, a Nordic expert group in
      social insurance and insurance medicine has compared important aspects of the
      Nordic schemes. RESULTS: The Nordic sickness benefit schemes have many
      similarities, but differ considerably in degree of compensation, with 100%
      coverage of salary in Denmark and Norway and less coverage in the other three
      countries. The length of the self certification period varies from 1 to 14 days.
      Longer sickness absence have to be certified by a doctor, usually the family
      physician. To counteract the increasing costs for sickness benefits, the follow
      up of sick-listed persons is being intensified. Efforts are also directed towards
      earlier and more extensive medical and vocational rehabilitation. So far these
      efforts have had only marginal effect on sickness absence and disability
      pensioning. INTERPRETATION: Basic needs for social security are still met by
      public insurance schemes in all Nordic countries. Private insurance schemes
      complement these to varying extent.

PMID- 12190053
TI  - Perceived risks of certain types of cancer and heart disease among Asian American
      smokers and non-smokers.
AB  - This study assessed knowledge levels of health risks of tobacco use among the
      Asian American (AA) community in the Delaware Valley region of Pennsylvania and
      New Jersey, including metropolitan Philadelphia. A cross-sectional self-report
      survey was conducted to collect the information, and a stratified-cluster
      proportional sampling technique was used to obtain a representative sample size
      of the target population of Chinese, Korean, Vietnamese, and Cambodians. 1374 AA
      were recruited from 26 randomly selected community organization clusters; of the
      total recruited, 1174 completed the survey, which consisted of 410 Chinese, 436
      Korean, 196 Vietnamese, 100 Cambodian and 32 other-group. Other-group was
      excluded for this study. Ten questions were asked to determine the knowledge
      level of the sample population. Results indicated that the vast majority of
      respondents (82.2%) recognized the association between smoking and increased risk
      of developing various types of cancers and heart disease. Between 81.3% and 93.3%
      of respondents recognized the increased risk for lung, mouth, throat.and
      esophageal cancer and heart disease. For these variables, there were
      statistically significant differences between the ethnic groups: Koreans were the
      most knowledgeable, followed by Chinese, Vietnamese, and Cambodians. For bladder,
      pancreatic, cervical, and kidney cancers, the percentage of respondents
      indicating an association between these cancers and smoking ranged from 49.2 to
      56.8. There were no statistically significant differences among the four ethnic
      groups for these variables. Generally, however, results showed that the awareness
      level was higher among women and the more educated respondents, non-smokers and
      former smokers, and Chinese and Korean groups.

PMID- 12190054
TI  - The role of the home environment in the transmission of infectious diseases.
AB  - The purpose of this paper is to examine current health care literature (1980
      2000) regarding the microbiology of the home environment, to summarize evidence
      of transmission within the home, and to assess effectiveness of cleaning
      practices and products. The home environment, particularly the kitchen and
      bathroom, serves as a reservoir of large numbers of microorganisms, particularly
      Enterobacteriacae, and infectious disease transmission has been demonstrated to
      occur in 6-60% of households in which one member is ill. Current food preparation
      and cleaning practices provide multiple opportunities for intra-household member
      spread. Routine cleaning is often sufficient, but in cases of household
      infection, may not adequately reduce environmental contamination. The
      effectiveness of disinfectants varies considerably and depends on how they are
      used as well as their intrinsic efficacy. The behavioral aspects of infection
      prevention in the home (e.g., foodhandling and cleaning practices) warrant
      increased public attention and education.

PMID- 12190055
TI  - Does knowledge count? Attitudes toward smoking among medical, nursing, and
      pharmacy students in Hungary.
AB  - Despite the fact that cigarette smoking in East Europe is a major health problem,
      no effective health policy responses have been developed thus far. Health care
      professionals represent a valuable resource for tobacco control. Therefore, we
      wanted to obtain information about the acceptance of smoking among medical,
      nursing and pharmacy students (n = 270) in Szeged, Hungary. The self-administered
      questionnaire contained items on smoking behavior, beliefs and attitudes related
      to smoking. Chi2-test were used to determine differences in the attitudes among
      students. Smoking was the most frequent among nursing students, followed by
      medical students. Pharmacy students not only reported smoking the least but they
      also showed the most acceptable attitudes toward smoking. The high frequency of
      smoking among students suggests that they themselves are unable to cope with
      avoiding the dangers of smoking. Moreover, responses reflect a generally poor
      appreciation of responsibility that health care professionals have in prevention.
      There is a need for an increasing emphasis on smoking-related attitude formation
      among medical and nursing students.

PMID- 12190056
TI  - Effectiveness of an intervention to increase Pap test screening among Chinese
      women in Taiwan.
AB  - This study assessed the effectiveness of a theory-based direct mail campaign in
      encouraging non-compliant women, aged 30 and older or younger if married, to
      obtain a Pap test. Participants were female family members of inpatients admitted
      to one of the major teaching hospitals in Taiwan during August-September 1999. A
      total of 424 women were recruited in the randomized intervention trial. Three
      months following implementation of the intervention, women in the intervention
      group reported a higher rate of Pap test screening than women in the comparison
      group (50% versus 32%) (p = 0.002). Women in the intervention group also showed
      higher perceived pros of a Pap test at follow-up (p = 0.031). Although women in
      both groups showed an increased knowledge and intention to obtain a Pap, only the
      intervention group had significantly higher follow-up scores on perceived pros
      and susceptibility. The results shows that the intervention was effective in
      increasing Pap test screening among Chinese women within three months. The
      results also support the use of Intervention Mapping, a systematic program
      development framework for planning effective interventions.

PMID- 12190057
TI  - Factors related to pharmacists' over-the-counter recommendations.
AB  - The primary purpose of this study was to investigate influences on pharmacists'
      over-the-counter (OTC) recommendations. A structured survey questionnaire
      covering medical, social, and marketing factors related to eight OTC product
      categories was designed and reviewed by a jury of experts and subsequently mailed
      to one-half of the 1440 pharmacies in Indiana. A total of 526 pharmacists
      responded to the questionnaire, providing a 73.1% response rate. Findings
      revealed that pharmacists were most likely to make favorable OTC recommendations
      related to nutritional supplements and smoking cessation products. Results also
      indicated that medical forces were significantly more important in influencing
      OTC product decisions than social and marketing forces. Based on the findings in
      this study, pharmacists are making OTC product recommendations in accordance with
      their health care training and expertise.

PMID- 12190058
TI  - Psychological, emotional studies of Mir space station missions show Russians
      fared better than Americans.

PMID- 12190059
TI  - Moving through fluids.

PMID- 12190061
TI  - Investigating gender differences under conditions of fatigue in a simulated high
      G aerial combat environment.
AB  - Advances in technology have equipped high-performance combat aircraft with the
      capability of delivering higher and higher sustained acceleration or G-forces on
      the pilots flying them. While the physiological effects of increased g-forces on
      the human body continue to be investigated, studies examining the effects of
      acceleration on the cognitive abilities of high-performance aircraft pilots
      remain sparse. Additionally, as higher technology is making its way into the
      cockpit, so are female pilots. With even fewer studies investigating women's
      physiological and cognitive tolerances to the stressors in the high-performance
      cockpit and flight environment, Dr. Chelette's study aimed to investigate these
      issues. Examining pilot workload, flight task abilities, and the effects of
      sleeplessness on both male and female pilots, Dr. Chelette's results revealed
      findings that will make their way into the high-performance cockpit of the
      future.

PMID- 12190060
TI  - Deviance among expeditioners: defining the off-nominal act through space and
      polar field analogs.
AB  - The space venture resembles other extreme environmental exploration in many
      respects. Since the beginning of the space program, social and behavioral
      scientists have predicted that space crews increasingly will begin to experience
      the kinds of deviant behaviors seen in other extreme environmental duty settings
      as mission duration, crew size, and heterogeneity increases. However, there has
      been a long history of neglect by the nation's space agency of those psychosocial
      human factors which will play such a vital role in future manned spaceflight. The
      author argues that this is counterproductive, even dangerous, and that social and
      behavioral studies must be conducted to generate baseline data regarding
      dysfunctional acts in extreme environments, including the milieu of the space
      mission. An obstacle to studying occurrences and frequencies of deviant acts is
      the absence of a standardized definition of such acts in the extreme environment.
      Borrowing the sanitized NASA term "off-nominal", which generally refers to a
      maladaptive action, a preliminary reliability test was conducted among five
      scientists who work with human interaction in extreme environments. They were
      asked to rate situations from several actual space and polar expeditions for
      numbers of off-nominal acts. They were told the object of the exercise was to
      derive a standardized definition and were not provided with any specific
      definition of off-nominality. Substantial agreement in their ratings provided
      reliable information to construct a working definition of off-nominality. Various
      interactions and behaviors which respondents deemed off-nominal could be subsumed
      under poor expertise, mental disorder, forms of abuse and interpersonal
      insensitivity, problems of authority and responsibility, task deficits, poor
      hygiene and fitness, poor field-base communication, and human error with
      equipment from violating safety procedures and poor judgment as to its usage.

PMID- 12190062
TI  - Astronaut draws attention to psychology, communication.

PMID- 12190063
TI  - Lucid showed pluck on long space mission.

PMID- 12190064
TI  - Blaha suggests need for future research on the effects of isolation and
      confinement.

PMID- 12190065
TI  - Moscow, we have a problem . . . Linenger's eventful stay aboard Mir.

PMID- 12190066
TI  - [At what age did our ancestors die?].

PMID- 12190067
TI  - The quest for anesthetic depth: Albert Faulconer, electroencephalography and the
      servo-controlled anesthesia machine.

PMID- 12190068
TI  - The syringe: getting to the point.

PMID- 12190069
TI  - Oriental medicine as a heterogeneous ensemble.

PMID- 12190070
TI  - [A study on the pillages of the Korean rural villages under the rule of Japanese
      Imperialism and the Research Institute for Rural Health].
AB  - The pillages of the Korean rural villages by force under the rule of Japanese
      imperialism resulted in the extreme impoverishment of the Korean agricultural
      communities. Especially this was accelerated due to starvation, ignorance and the
      poor sanitary conditions on the part of the Korean farmers. The research
      institute of agricultural community hygiene founded by a Korean doctor, Young
      Choon Lee was the beginning of the rural medical institute that contributed
      greatly to the disease prevention and health improvements of impoverished
      farmers.

PMID- 12190072
TI  - [The medical system and its characteristics during the Koryo Dynasty period].
AB  - This article explores the medical system of the Koryo Dynasty period and its
      social characteristics. First, the structure of medical system and roles of
      medical institutions during the Koryo Dynasty period will be summarized. Then,
      the characteristics of the medical system will be identified through exploring
      the principles of its formation in a view of social recognition of medical care
      and a view of public policy. During the Koryo Dynasty period, medical experts
      were trained in national education institutions from the early days of Dynasty.
      After trained, they were appointed to the posts at government service with their
      medical profession. In the meantime, they sought ways to ascend their social
      position. Physicians of Oriental medicine were appointed to the posts at each
      local government and troops to take charge of medical treatments of the common
      people. Also, the state tried to assume the reins of medical system by actively
      taking part in circulation (collection and distribution) of herb. Taeuigam and
      Sangyakguk represent central medical institutions of the Koryo, taking charge of
      medical service for the aristocracy and the bureaucracy. The Common people were
      treated at DongSeoDaeBiWOn, JeWuiBo, HyeMinGuk, and YakJum in SeoKyung. However,
      activities of these institutions became less active around the days of military
      officials regime, as officers became negligent and financial base went broken.
      The roles of medical institutions of the Koryo government were not restricted to
      the treatment of diseases. Policies for the common people were constituted by two
      main policies, the policy for encouraging agriculture and the policy for giving
      relief to people. Medical institutions, with other social systems, had a social
      responsibility to support the governing system of the Koryo and maintain the
      stability of the society. In this aspect, medical institutions such as
      DongSeoDaeBiWon and JeWuiBo, and relief institutions such as UiChang, were all
      related and connected organically, and they were results of, and bases of the
      relief policy. However, medical system for the common people was made up first
      for practical needs and then improved successively. Allocation of medical experts
      and execution of relief work were carried out by each local government, except
      the case of serious disaster, which central government took part in. As the Koryo
      Dynasty went into its latter period, temporary institutions and one - time
      benefits replaced permanent institutions. These four characteristics described
      above were systemic characteristics of medical system during the Koryo Dynasty
      period.

PMID- 12190071
TI  - [The Gurhigae Jejoongwon: its size and activities].
AB  - This article explores the location, size of the site, and medical activities of
      the Gurhigae Jejoongwon. Relevant documents such as reminiscences, diplomatic
      notes, newspaper accounts, maps, and photographs were referred for this study.
      The Gurhigae Jejoongwon located on a hill that, at present, covers the area from
      Ulchi-ro to MyungDong Cathedral. Its main entrance was towards Ulchi-ro. Real
      estate including the buildings of the Gurhigae Jejoongwon was returned to the
      Chosun government in 1905, and the estimated size of its site varied from 1,810
      pyung to 5,036 pyung. The site of the Gurhigae Jejoongwon was 2 - 5 times larger
      than the 862.16-pyung-site of the Jejoongwon in its Jaedong days. With such
      larger size, the Jejoongwon could take care of more patients. Dr. Avison started
      medical education again. The Gurhigae Jejoongwon took the central part in medical
      treatment activities for public in Seoul, as it carried out the prevention
      activities against Cholera in 1895. The Chosun government highly recognized its
      medical treatment activities for the common people.

PMID- 12190073
TI  - Flight controller alertness and performance during spaceflight shiftwork
      operations.
AB  - Decreased alertness and performance associated with fatigue, sleep loss, and
      circadian disruption are issues faced by a diverse range of shiftwork operations
      personnel. During Space Transportation System (STS) operations, Mission
      Operations Directorate (MOD) personnel provide 24-hr. coverage of critical tasks.
      A joint NASA Johnson Space Center and NASA Ames Research Center project was
      undertaken to examine these issues in flight controllers during MOD shiftwork
      operations. An initial operational test of procedures and measures was conducted
      during the STS-53 mission in December 1992. The study measures included a
      Background Questionnaire, a subjective daily logbook completed on a 24-hour basis
      (to report sleep patterns, work periods, etc.), and an 8 minute performance and
      mood test battery administered at the beginning, middle, and end of each shift
      period. Seventeen flight controllers representing the 3 Orbit shifts
      participated. The initial results clearly support the need for further data
      collection during other STS missions to document baseline levels of alertness and
      performance during MOD shiftwork operations. Countermeasure strategies specific
      to the MOD environment are being developed to minimize the adverse effects of
      fatigue, sleep loss, and circadian disruption engendered by shiftwork operations.
      These issues are especially pertinent for the night shift operations and the
      acute phase advance required for the transition of day shift personnel into the
      night for shuttle launch. Implementation and evaluation of the countermeasure
      strategies to maximize alertness and performance is planned. As STS missions
      extend to further EDO (extended duration orbiters), and timelines and planning
      for 24-hour Space Station operations continue, alertness and performance issues
      related to sleep and circadian disruption will remain highly relevant in the MOD
      environment.

PMID- 12190074
TI  - Human and team performance in extreme environments: Antarctica.
AB  - Analogous experience is often instructive when attempting to understand human
      behavior in extreme environments. The current paper refers to the experiences of
      polar explorers and remote duty personnel to help identify the factors that
      influence individual and team performance when small groups are isolated and
      confined for long durations. The principal factors discussed include
      organizational structure, intracrew communications, interpersonal relations,
      leadership style, personnel selection, and training. Behavioral implications also
      are addressed for the design of procedures and equipment to facilitate sustained
      individual and group performance under conditions of isolation and confinement.
      To be consistent with the theme of the symposium, this paper emphasizes the crew
      requirements for an international expedition to Mars.

PMID- 12190075
TI  - Testing and evaluation for astronaut extravehicular activity (EVA) operability.
AB  - Because it is the human component that defines space mission success, careful
      planning is required to ensure that hardware can be operated and maintained by
      crews on-orbit. Several methods exist to allow researchers and designers to
      better predict how hardware designs will behave under the harsh environment of
      low Earth orbit, and whether designs incorporate the necessary features for Extra
      Vehicular Activity (EVA) operability. Testing under conditions of simulated
      microgravity can occur during the design concept phase when verifying design
      operability, during mission training, or concurrently with on-orbit mission
      operations. The bulk of testing is focused on normal operations, but also
      includes evaluation of credible mission contingencies or "what would happen if"
      planning. The astronauts and cosmonauts who fly these space missions are well
      prepared and trained to survive and be productive in Earth's orbit. The
      engineers, designers, and training crews involved in space missions subject
      themselves to Earth based simulation techniques that also expose them to extreme
      environments. Aircraft falling ten thousand feet, alternating g-loads, underwater
      testing at 45 foot depth, enclosure in a vacuum chamber and subject to thermal
      extremes, each carries with it inherent risks to the humans preparing for space
      missions.

PMID- 12190076
TI  - Astronaut's perception of heaviness and limb position.

PMID- 12190077
TI  - Habitability and performance issues for long duration space flights.
AB  - Advancing technology, coupled with the desire to explore space has resulted in
      increasingly longer manned space missions. Although the Long Duration Space
      Flights (LDSF) have provided a considerable amount of scientific research on
      human ability to function in extreme environments, findings indicate long
      duration missions take a toll on the individual, both physiologically and
      psychologically. These physiological and psychological issues manifest themselves
      in performance decrements; and could lead to serious errors endangering the
      mission, spacecraft and crew. The purpose of this paper is threefold: 1) to
      document existing knowledge of the effects of LDSF on performance, habitability,
      and workload, 2) to identify and assess potential tools designed to address these
      decrements, and 3) to propose an implementation plan to address these
      habitability, performance and workload issues.

PMID- 12190078
TI  - Prenatal diagnosis in Alberta: practices and attitudes of referring physicians.

PMID- 12190079
TI  - Are we there yet? The representation of women as subjects in clinical research.

PMID- 12190080
TI  - Concerns for a multicultural crew aboard the International Space Station.

PMID- 12190081
TI  - Introduction to cognitive processes of expert pilots.
AB  - This report addresses the historical problem that a very high percentage of
      accidents have been classified as involving "pilot error." Through extensive
      research since 1977, the Federal Aviation Administration determined that the
      predominant underlying cause of these types of accidents involved decisional
      problems or cognitive information processing. To attack these problems,
      Aeronautical Decision Making (ADM) training materials were developed and tested
      for ten years. Since the publication of the ADM training manuals in 1987,
      significant reductions in human performance error (HPE) accidents have been
      documented both in the U.S. and world wide. However, shortcomings have been
      observed in the use of these materials for recurrency training and in their
      relevance to more experienced pilots. The following discussion defines the
      differences between expert and novice decision makers from a cognitive
      information processing perspective, correlates the development of expert pilot
      cognitive processes with training and experience, and reviews accident scenarios
      which exemplify those processes. This introductory material is a necessary
      prerequisite to an understanding of how to formulate expert pilot decision making
      training innovations; and, to continue the record of improved safety through ADM
      training.

PMID- 12190082
TI  - Analyzing cockpit communications: the links between language, performance, error,
      and workload.
AB  - The importance of communication on the flightdeck is discussed and the
      application of a new computer-based linguistic method of text analysis is
      introduced. Preliminary results from a NASA B727 simulator study indicate that
      specific language variables are moderately to highly correlated with individual
      performance, individual error rates, and individual communication ratings. Also,
      language use was found to vary as a function of crew position and level of
      workload during the flight. Use of the first person plural (we, our, us)
      increases over the life of a flightcrew, and Captains speak more in the first
      person plural than First Officers or Flight Engineers. Language use in initial
      flights was associated with performance and error in subsequent flights. These
      are preliminary data, in that this method of linguistic analysis is currently
      being developed and integrated with a content-coding method of communication
      analysis and models of threat and error.

PMID- 12190083
TI  - Treatment of patients with uncomplicated gallbladder stones?

PMID- 12190084
TI  - Stool test with polyclonal antibodies for monitoring Helicobacter pylori
      eradication in adults: a critical reappraisal.

PMID- 12190085
TI  - Effects of anaesthetic agents on gastrin-stimulated and histamine-stimulated
      gastric acid secretion in the totally isolated vascularly perfused rat stomach.
AB  - BACKGROUND: Anaesthetic agents affect gastric acid secretion, but the mechanisms
      behind this action have not been fully evaluated. The enterochromaffin-like (ECL)
      cell plays a key role in the regulation of gastric acid secretion, and
      anaesthetic agents have recently been described as inhibiting histamine release
      from the ECL cell. The present study examines the effect of anaesthetic agents on
      the ECL cell and on parietal cell functions. METHODS: Different concentrations of
      urethane, pentobarbital and a mixture of fluanisone/fantanyl/midazolam (FFM) were
      examined for the effect on gastrin-stimulated histamine release and acid
      secretion and on histamine-stimulated acid secretion in the totally isolated
      vascularly perfused rat stomach. The luminal acid output and histamine
      concentrations in venous effluents were measured by titration and
      radioimmunoassay, respectively. RESULTS: Pentobarbital caused an inhibition on
      both histamine release and acid output in gastrin-stimulated stomachs in a
      concentration-dependent way. The mixture of FFM at higher concentrations
      inhibited histamine release from the ECL cell and luminal H+ output in gastrin
      stimulated acid secretion. Urethane exerted a slight inhibitory effect on
      histamine release only at the lowest concentration. Pentobarbital also reduced
      histamine-stimulated gastric acid secretion, while the mixture of FFM did not.
      CONCLUSIONS: pentobarbital inhibits acid secretion both by reducing ECL cell
      histamine release and parietal cell H+ secretion, whereas FFM inhibits acid
      secretion by interaction with the ECL cell only. Urethane also had a slight
      inhibitory effect on the ECL cell histamine release at the lowest concentration.

PMID- 12190086
TI  - Different role of the histamine H3-receptor in vagal-, betanechol-, pentagastrin
      induced gastric acid secretion in anaesthetized rats.
AB  - BACKGROUND: To date, involvement of the histamine H3-receptor in the control of
      gastric acid secretion in rats is not conclusively defined because of the
      variability of experimental results. This study was therefore aimed at
      investigating the role of H3-receptors in acid secretion produced by nervous or
      pharmacological stimulation in anaesthetized rats. METHODS: Gastric acid output
      was measured by flushing the rat stomach lumen with 5 ml saline and titrating the
      flushed perfusate. Hypersecretory responses were evoked through direct vagal
      stimulation (0.5 msec, 10 Hz, 50 V for 30 min every 30 min) or by stimulation
      with pentagastrin (20, 40, 100, 250 microg/kg/h i.v.) or betanechol (100, 250,
      500 microg/kg/h i.v.). The selective H3 ligands (R)-alpha-methylhistamine and
      thioperamide (100 microg/kg i.v.) were tested alone or in combination on both
      basal and electrically/pharmacologically induced secretion. RESULTS: Vagally
      induced response was significantly reduced by the agonist R-alpha-methylhistamine
      and this effect was antagonized by the antagonist thioperamide at a dose unable
      by itself to modify vagal response. Thioperamide significantly increased acid
      response only on pentagastrin low dose (20 microg/kg/h) and this effect was
      counteracted by R-alpha-methylhistamine, which was ineffective when administered
      alone. Betanechol-induced hypersecretion was substantially unaffected by the H3
      ligands, which were also inactive on basal acid output. CONCLUSIONS: Although
      this functional study confirms the presence of histamine H3-receptors in the rat
      stomach, they appear to have minor weight in regulation of the acid secretion in
      this species.

PMID- 12190087
TI  - Roles of cytoskeleton and tyrosine receptor mediated signal transduction in the
      restitution of isolated guinea pig gastric mucosa.
AB  - BACKGROUND: The immediate response of the GI-epithelium to a superficial injury
      is primarily directed to restore the disturbed epithelial continuity in a process
      called restitution. The involvement of both structural (cytoskeleton) and humoral
      (growth factors and cytokines) signal transduction systems in the process has
      been documented. Previously, in experimental circumstances the role of the two
      systems has been examined as two distinct units. Nevertheless, in normal
      conditions in vivo, the two systems are presumably acting simultaneously. This
      study investigates the functional roles of cytoskeleton and tyrosine receptor
      mediated signalling in the regulation of restitution. METHODS: Guinea pig gastric
      mucosa was mounted in Ussing-chamber, injured with 1.25 M NaCl and subsequently
      perfused for 4 h. Simultaneously, the electrophysiological resistance of the
      tissue (R) was recorded. During the recovery, the tissue was exposed bilaterally
      either to modulators of cytoskeleton (cytochalasin B/lysophosphatidic acid) or of
      tyrosine receptor mediated signalling (genistein/epidermal growth factor +
      transforming growth factor-alpha). After the experiment, the tissue was analysed
      morphologically and the proliferative index (PI) was determined morphometrically.
      RESULTS: Exposure of the tissue to cytochalasin caused a significant decrease of
      both restitution (tissue resistance) and proliferation (PI), whereas simultaneous
      treatment with EGF+ TGFalpha restored both restitution and proliferation.
      Correspondingly, exposure of the tissue to genistein during restitution impaired
      the process as well as induction of proliferation, while simultaneous exposure to
      lysophosphatidic acid restored the processes. Exposure of the tissue to EGF+
      TGFalpha and lysophosphatidic acid simultaneously resulted in a mild, but
      insignificant additive inductions of both restitution and proliferation.
      CONCLUSIONS: Restitution is controlled by both structural and humoral signalling
      systems. If one of the regulating systems fails, stimulation of the other
      restores the process. Simultaneous stimulation of both systems has a minor
      additive effect on both restitution and proliferation.

PMID- 12190088
TI  - Additive effects of Helicobacter pylori lipopolysaccharide and proteins in
      monocyte inflammatory responses.
AB  - BACKGROUND: Chronic active gastritis associated with Helicobacter pylori
      infection is characterized by both a neutrophil and a mononuclear leukocyte
      infiltrate. While neutrophil functions in relation to H. pylori are well
      described, the interactions between Helicobacter bacterial factors and monocytes
      are poorly understood in relation to the mucosal inflammatory process. METHODS:
      Sonicates of a clinical strain as well as of a type strain of H. pylori were
      prepared in vitro. Monocytes from healthy donors were induced to release L
      selectin (CD62L), to upregulate the adherence molecules (CD11a, CD11b. CD11c) and
      to produce toxic oxygen radicals. The inducing activities were assessed by flow
      cytometry and chemiluminescence. RESULTS: A dose-dependent shedding of CD62L and
      upregulation of CD11b and CD11c were observed with both bacterial strains as well
      as PMA and fMLP. CD11a remained unchanged. Activity could be attributed to
      bacterial factors of both lipopolysaccharide (LPS) and protein characteristics.
      The alterations observed for CD11b, CD11c and CD62L were induced by the same
      protein fractions in parallel. suggesting a common component and mechanism of
      action. A major protein component was urease, although other minor protein bands
      were found as well. Monoclonal antibodies to CD14-inhibited monocyte inflammatory
      responses induced by H. pylori sonicate at low concentration, whereas further LPS
      pierce-matrix reduction was necessary at high sonicate concentrations to reduce
      monocyte-inducing activity. CONCLUSIONS: Monocyte inflammatory activation is
      induced by H. pylori sonicate components. Factors of both LPS and protein
      characteristics are involved and an additive effect was demonstrated. Urease
      appears to be a major component in the protein preparations of highest inducing
      capacity. Further studies are warranted to assess whether the monocyte activation
      properties described here are related to the diversity of clinical gastroduodenal
      outcome for the chronic type B gastritis associated with H. pylori infection.

PMID- 12190089
TI  - Carditis: all Helicobacter pylori or is there a role for gastro-oesophageal
      reflux?
AB  - BACKGROUND: Recent epidemiological studies have reported a threefold increase in
      the incidence of adenocarcinoma of the lower oesophagus and gastro-oesophageal
      junction (cardia). There are conflicting reports available implicating both
      gastro-oesophageal reflux disease and Helicobacter pylori infection in the
      aetiology of carditis and cardia intestinal metaplasia, despite strong evidence
      to show that these two conditions are, if anything, inversely related. We aimed
      to determine the prevalence of carditis and cardia intestinal metaplasia in
      dyspeptic subjects and also their association with H. pylori infection and gastro
      oesophageal reflux disease. METHOD: Histological samples from the gastric cardia
      were obtained from dyspeptic subjects. H. pylori status was assessed based on
      histological, microbiological and rapid urease testing. Gastro-oesophageal
      disease was diagnosed on the basis of histological evidence and/or erosive
      oesophagitis. Patient demographics were recorded. Cardia intestinal metaplasia
      (CIM), when present, was subgrouped as complete or incomplete. RESULTS: Overall,
      276 subjects were enrolled; 163 (59%) had carditis and 36 (13%) CIM. H. pylori
      infection and gastro-oesophageal reflux disease occurred in 64 (23%) and 150
      (54%), respectively. H. pylori infection was strongly associated with carditis
      and CIM (P<0.001 and P<0.01). Older age and male gender were also associated with
      inflammation and intestinal metaplasia of the cardia. Gastro-oesophageal reflux
      was not associated with either entity. CONCLUSION: Carditis and CIM occur
      frequently. Both conditions are strongly associated with H. pylori infection,
      older age and male gender. There was no association with gastro-oesophageal
      reflux disease.

PMID- 12190090
TI  - Helicobacter pylori and different topographic types of gastritis: treatment
      response after successful eradication therapy in functional dyspepsia.
AB  - BACKGROUND: Helicobacter pylori gastritis is usually a lifelong disease which can
      cause different topographical inflammatory reactions and induce divergent effects
      on acid secretion in humans. High acid output and antrum-predominant gastritis
      are associated with duodenal ulcer disease, whereas corpus-predominat gastritis
      has been associated with low acid output and risk of gastric carcinoma. The
      objective of this study was to evaluate the role of different gastritis subtypes
      in the long-term treatment response of H. pylori-positive functional dyspepsia.
      METHODS: The gastric biopsies from 143 H. pylori-positive patients with
      functional dyspepsia were classified in accordance with the Sydney System as
      antrum-predominant gastritis, pangastritis or corpus-predominant gastritis. The
      patients were randomized to receive either eradication therapy or placebo
      antibiotics. Moreover, to standardize acid suppression every patient received
      omeprazole therapy for the first 3 months. Dyspeptic symptoms were evaluated from
      a questionnaire and the follow-up time was 12 months. In addition, delta-over
      baseline (DOB) values of the 13C-urea breath test (UBT) were analysed from a
      subgroup of 36 patients to measure urease activity of the stomach. RESULTS: After
      1 year, the dyspepsia symptom score was 7.4 +/- 3.0 (95% CI 6.6-8.2) in
      successfully H. pylori-eradicated patients and 7.6 +/- 3.1 (95% CI 6.9-8.4) in
      controls (P = ns). Among patients with antrum-predominant gastritis, dyspepsia
      score was reduced more in subjects whose H. pylori was eradicated than in
      controls with ongoing infection (-3.6 +/- 2.9 versus -1.7 +/- 2.9; P = 0.05).
      High urease activity of the stomach was associated with severe or moderate
      chronic antrum-predominant gastritis. CONCLUSIONS: Patients with antrum
      predominant H. pylori-positive chronic gastritis and functional dyspepsia get
      symptom improvement after successful eradication therapy. A high DOB value of UBT
      is associated with these patients.

PMID- 12190091
TI  - Serum levels of amidated gastrin-17 and pepsinogen I in atrophic gastritis: an
      observational case-control study.
AB  - BACKGROUND: Helicobacter pylori infection is often diagnosed with non-endoscopic
      methods, such as serology or breath or antigen stool tests. These tests provide
      information on the presence or absence of the H. pylori gastritis only. We
      investigated whether atrophic gastritis can be diagnosed and typed non
      endoscopically if the serum levels of pepsinogen I (S-PGI) and gastrin-17 (S-G
      17) are assayed in connection with H. pylori testing. METHODS: The present
      investigation is an observational case-control study comprising 100 selected
      dyspeptic outpatients with (cases) or without (controls) advanced (moderate or
      severe) atrophic gastritis. Before the blood tests, all patients underwent a
      diagnostic gastroscopy with multiple biopsies. The series of cases includes 56
      patients. Eight had an advanced antrum limited atrophic gastritis, 13 had
      resected antrum (in two of whom the corpus mucosa in the stump was atrophic), and
      30 had corpus-limited atrophic gastritis. Four patients had an advanced atrophic
      gastritis in both the antrum and corpus (multifocal atrophic gastritis), and the
      whole stomach was removed in one patient. Twenty of the 44 controls had a non
      atrophic H. pylori gastritis. Both the antrum and corpus were normal and healthy
      in 24 patients. The S-PGI and S-G-17 were determined with EIA methods using
      monoclonal antibodies to PGI and amidated G-17. Postprandial S-G-17 (S-G-17prand)
      was measured 20 min after a protein-rich drink. The H. pylori antibodies were
      assayed with a polyclonal EIA method. RESULTS: A low S-PGI (<25 microg/l; an
      empirical cut-off with best discrimination) was found in 31 of 37 patients (84%)
      with and in 3 of 63 patients (5%) without corpus atrophy in the biopsy specimens.
      A low S-G-17prand (<5 pmol/l) was found in all 8 patients with H. pylori
      associated antral atrophy and in 11 of 14 patients (79%) with resected antrum but
      in 3 of 20 control patients (15%) with H. pylori-related non-atrophic gastritis.
      Median and mean values of both S-G-17prand and S-PGI decreased with increasing
      grade of antral and corpus atrophy, respectively. Among all patients with
      atrophic gastritis (multifocal atrophic gastritis, or atrophic gastritis limited
      to antrum or corpus) or resected stomach, 50 of 56 patients (89%; Cl 95%: 81%
      97%) had a low S-PGI and/or a low S-G-17prand with positive H. pylori serology.
      Such low values werc found in 3 of the 44 control patients (7%; CI 95%: 0%-14%).
      CONCLUSIONS: Low serum levels of G-17prand and PGI are conceivable biomarkers of
      atrophic antral and corpus gastritis, respectively. A low S-G-17prand is a sign
      of the multifocal or antrum-limited atrophic gastritis in patients infected with
      H. pylori.

PMID- 12190092
TI  - Metabolic characteristics of the faecal microflora in humans from three age
      groups.
AB  - BACKGROUND: Little is known about the influence of the ageing process on the
      bacterial metabolism. The aim of this work was to study the inter-individual
      variation and the influence of age on metabolic characteristics of the faecal
      microflora from persons of three age groups. METHODS: Nine enzyme activities and
      11 metabolites were analysed in faecal samples of 21 elderly persons (69-89 years
      of age), 15 adults (30-46 years of age) and 14 children (3-15 years of age).
      RESULTS: They provide a pattern of the faecal microflora metabolism in a French
      population aged between 3 and 89 years. They showed large inter-individual
      differences in the three groups. Although the enzyme activities were not
      significantly different between groups, glycolytic activities appeared less
      variable in adults than in elderly persons and children. The major metabolites
      (acetate, propionate, butyrate and L-lactate) resulting from carbohydrate
      fermentation were similar in the three groups. Samples from elderly persons were
      characterized by higher D/L lactate ratio and higher concentrations of
      metabolites resulting from protein fermentation (ammonia, valerate, iso-butyrate
      and iso-valerate). CONCLUSION: The data showed significant differences between
      elderly persons and younger adults and children, but the major metabolic
      characteristics of the faecal microflora were not greatly altered by the ageing
      process.

PMID- 12190094
TI  - Intestinal permeability and absorptive capacity in children with portal
      hypertension.
AB  - BACKGROUND: Portal hypertension may affect intestinal function leading to
      malnutrition in children with liver disease. The aim was to determine whether
      children with portal hypertension with or without liver disease had impaired
      absorptive capacity and intestinal barrier function (intestinal permeability) and
      to ascertain whether these abnormalities related to changes in body composition.
      METHODS: Twenty-six children with portal hypertension were divided according to
      aetiology into: Group 1 intrahepatic (n = 15) and Group 2 prehepatic (n = 11).
      Thirty-five children acted as controls. Carbohydrate absorption and intestinal
      permeability were assessed using a sugar absorption/permeability test and a
      variety of anthropometric measurements were obtained. RESULTS: 3-O-methyl-D
      glucose, D-xylose and L-rhamnose excretion were significantly reduced in both
      patient groups compared to controls (P < or = 0.008) and the differential urinary
      excretion of melibiose/rhamnose (intestinal permeability) was significantly
      increased in Group 1 only (P < 0.05). Anthropometric measurements showed low Z
      scores in both groups, but there was no significant (P > 0.05) difference between
      them. There was no significant correlation between urinary excretion of sugars.
      anthropometric measurements and energy intake. CONCLUSIONS: Increased portal
      pressure reduces the absorptive capacity of the small intestine, while liver
      disease itself leads to increased intestinal permeability.

PMID- 12190093
TI  - Water absorption enhances the uptake of mannitol and decreases Cr-EDTA/mannitol
      permeability ratios in cat small intestine in situ.
AB  - BACKGROUND: Recently, we hypothesized that mannitol absorption in human
      intestinal permeability tests is a reflection of small intestinal water
      absorption and is dependent mainly on the efficiency of the countercurrent
      multiplier in the villi. This may affect the outcome of clinical double-sugar
      permeability tests. We tested the hypothesis in cats, another species with an
      efficient countercurrent multiplier. METHODS: The lumen-to-tissue transport of
      [14C]mannitol and [51Cr]EDTA was studied in in situ perfused jejunum of eight
      anaesthetized cats using four isotonic perfusion solutions with varying sodium
      and glucose content. The transport of water was monitored, and the absorption
      rate of the probes was calculated by their disappearance from the perfusate.
      RESULTS: There was a significant positive correlation between water absorption
      and [14C]mannitol clearance from the different perfusates (r = 0.99; P < 0.01),
      whereas this correlation was absent for [51Cr]EDTA clearance (r = 0.05; P =
      0.95). There was also a significant negative correlation between water absorption
      and [51Cr]EDTA/[14C]mannitol clearance ratios (r = 0.98; P < 0.02). CONCLUSIONS:
      The results show a prominent effect of water absorption on mannitol uptake
      through pores which, also during glucose transport, exclude Cr-EDTA. The
      difference in water absorption from the solutions used in cat small intestine is
      dependent on the effectiveness of the countercurrent multiplier; we conclude that
      the capability of this mechanism influences mannitol absorption in vivo.
      Qualitatively comparable results were obtained using oral test solutions with
      varying NaCl and glucose concentrations in human volunteers. We propose that the
      functioning of the countercurrent multiplier is essential for the interpretation
      of double-sugar tests in clinical studies.

PMID- 12190095
TI  - Gliadin is a good substrate of several transglutaminases: possible implication in
      the pathogenesis of coeliac disease.
AB  - BACKGROUND: Deamidation of distinct glutamines in HLA-DQ2 restricted gliadin
      epitopes, considered critical in the pathogenesis of coeliac disease (CD), can be
      mediated by tissue transglutaminase (tTG). To elucidate the possible role of
      other transglutaminases in CD we investigated whether different mammalian,
      microbial and vegetable transglutaminases can use gliadin as substrate. METHODS:
      Studies in which small amounts of transglutaminase have been measured have led to
      our modifying a microtitre plate assay. We used proteolytically digested gliadin
      as solid phase substrate and Europium-labelled streptavidine to quantify the
      biotinylated product covalently linked by the enzyme to the plate. RESULTS: The
      modified assay is ultrasensitive and quantitative, measuring guinea pig liver
      transglutaminase concentrations between 0.5 and 50 ng/well. The specific
      activities of the enzymes (counts/min/mg) against gliadin and N,N-dimethylcasein,
      respectively, are: tTG 9800/4900, Factor XIII 97330/55620, epidermal
      transglutaminase 47650/50770, streptoverticillium transglutaminase 4290/2200,
      phytophora cactorum transglutaminase 6910/4110. For the first time, we have
      detected transglutaminase activity in bean sprouts, spinach leaves and green
      peas, which are commonly used Vegetables. CONCLUSION: Gliadin is a good substrate
      for endogenous, microbial and plant transglutaminases. An interesting altemative
      is that gliadins are deamidated by microbial or food transglutaminases in the
      intestinal lumen. The assay described provides an ultrasensitive method for
      measuring small amounts of transglutaminase and is considered a helpful tool in
      further studies of the possible role of transglutaminases in the pathogenesis of
      CD.

PMID- 12190096
TI  - A positive response to infliximab in Crohn disease: association with a higher
      systemic inflammation before treatment but not with -308 TNF gene polymorphism.
AB  - BACKGROUND: Two-thirds to three-fourths of patients with either refractory
      luminal or fistulizing Crohn disease respond to infliximab treatment. The ability
      or inability to respond seems to persist over time. Biological characteristics
      and/or genetic background can influence the response to treatment. The aim was to
      assess the value of C-reactive protein and TNF-alpha serum levels before
      treatment as well as the TNF -308 gene polymorphism in the prediction of response
      to infliximab treatment in Crohn disease. METHODS: Two-hundred-and-twenty-six
      Crohn disease patients treated in the setting of an expanded access programme to
      infliximab in Belgium were studied. There were 136 refractory luminal diseases
      and 90 refractory fistulizing diseases. Luminal diseases were treated with one
      single infusion; fistulizing diseases with three infusions at weeks 0, 2 and 6. A
      clinical response to treatment was defined as either a Crohn disease activity
      index <150 (complete) or a drop of 70 points (partial) at week 4, for luminal
      disease, and as either complete fistula healing (complete) or a decrease of at
      least 50% of the number of draining fistulas on two consecutive visits between
      weeks 0 and 18, for fistulizing disease. CRP and serum TNF-alpha levels were
      measured at week 0 before treatment and were compared between responders and non
      responders. Patients were genotyped for the -308 TNF gene polymorphism, and
      allelic as well as genotype frequencies were compared between responders and non
      responders. RESULTS: There were 73.2% responders (46.4% complete and 26.8%
      partial) and 26.8% non-responders. Response rates were similar in luminal and
      fistulizing diseases. CRP level before treatment was significantly higher in
      responders than in non-responders (16.8 mg/l (5-160) versus 9.6 mg/l (5-143); P =
      0.02). Furthermore, response rate was significantly higher in patients with
      elevated CRP (>5 mg/l) than in patients with a normal CRP value (<5 mg/l) before
      treatment (76% versus 46%; P=0.004; OR: 0.26 (0.11-0.63)). Allelic and genotype
      frequencies for -308 TNF gene polymorphism were not significantly different
      between responders and non-responders--with the exception of a slightly higher
      TNF2 frequency in non-responders in luminal disease (22.1 % versus 11.6%; P =
      0.04). However, this was not associated with a significant difference in genotype
      frequencies. CONCLUSION: A positive clinical response to infliximab was
      associated with a higher CRP level before treatment in our population of Crohn
      disease patients, but there was no relevant association with -308 TNF gene
      polymorphism. We therefore suggest that CRP level may help to identify better
      candidates for infliximab treatment.

PMID- 12190097
TI  - High prevalence of Epstein-Barr virus in gastric remnant carcinoma after Billroth
      II reconstruction.
AB  - BACKGROUND: Epstein-Barr virus (EBV) has been detected in about 10% of gastric
      carcinoma cases worldwide, and a high prevalence of EBV involvement in gastric
      remnant carcinoma has been reported recently. Details of the background remnant
      stomach of EBV-positive lesions, however, have not been well clarified. METHODS:
      We screened 17 consecutive gastric remnant carcinoma lesions resected surgically.
      To detect EBV, we used in situ hybridization (ISH) for EBV-encoded small RNA1
      (EBER-1) and we compared the clinicopathologic feature between EBV-positive and 
      negative gastric remnant carcinoma cases. RESULTS: EBV was detected in 41.8% (7
      of 17) of the lesions by EBER-1 ISH. All 7 EBV-positive lesions developed in the
      anastomotic site had undergone Billroth-II reconstruction excess 20 years
      previously (mean 26.4 years). Histologically, all EBV-positive lesions were
      poorly differentiated adenocarcinomas with intense lymphocyte infiltration. In
      the adjacent mucosa of carcinomas, moderate or marked intestinal metaplasia was
      found in 85.7% (6 of 7) of EBV-positive lesions and in 40% (4 of 10) of EBV
      negative lesions. CONCLUSIONS: EBV infection is strongly associated with gastric
      remnant carcinoma. Atrophic change of remnant gastritis in Billroth-II
      anastomoses is considered to be the carcinogenic background for EBV-positive
      gastric remnant carcinoma.

PMID- 12190098
TI  - Profile of monocyte chemoattractant protein-1 circulating levels in gastric
      cancer patients.
AB  - BACKGROUND: Monocyte chemoattractant protein-1 (MCP-1) has been shown to act as a
      chemokine in the recruitment of monocyte/macrophages during inflammation states.
      It acts as an important factor in the cytokine network, which regulates tumor
      proliferation, whereas the association between serum MCP-1 level and gastric
      cancer has not yet been clarified. METHODS: The serum concentration of MCP-1 in
      76 gastric cancer patients and in 45 normal controls was determined using an
      immunoradiometric assay. The concentration of MCP-1 in the 47 cancer tissue
      samples was also determined. RESULTS: The serum concentration of MCP-1 in
      patients with advanced carcinoma was significantly lower than that in controls.
      The serum concentration of MCP-1 in patients with advanced carcinoma was
      significantly lower than that in patients with early carcinoma. The serum
      concentration of MCP-1 was associated with clinicopathological factors including
      lymph node metastasis, serosal invasion and histological differentiation of the
      tumor. In patients who underwent palliative surgery, the serum MCP-1 level
      significantly decreased postoperatively, whereas in patients who underwent
      curative surgery the serum MCP-1 level tended to increase. The 4-year survival
      rate in patients whose serum MCP-1 levels were lower than or equal to the median
      value was significantly lower than that in patients whose MCP-1 levels were
      higher than the median value. The tissue concentration of MCP-1 in the cancer
      tended to decrease in accordance with disease progression. CONCLUSIONS: The serum
      level of MCP-1 decreased in accord with disease progression, which reflects local
      consumption in gastric cancer. Serum MCP-1 may be a useful marker that reflects
      the host's local resistance to the tumor.

PMID- 12190099
TI  - Symptomatic, non-complicated gallbladder stone disease. Operation or observation?
      A randomized clinical study.
AB  - BACKGROUND: Cholecystectomy has been recognized as the treatment of choice for
      symptomatic gallbladder stone disease. Not all patients are cured by an operation
      and the reason for having the gallbladder removed may rest on common practice
      rather than evidence-based medicine. The aim was to compare cholecystectomy with
      observation (watchful waiting) in patients with uncomplicated symptomatic GBS
      disease. Three-hundred-and-thirty-eight patients were considered for
      participation in the study; 45 patients were excluded according to predefined
      criteria and 156 did not join for other reasons. The remaining 137 were
      randomized to cholecystectomy (n = 68) or non-operative, expectant treatment (n =
      69). METHODS: Randomized patients were contacted regularly and followed for a
      median of 67 months. All gallstone-related hospital contacts were registered in
      both randomized and excluded patients. RESULTS: Eight of the patients randomized
      to cholecystectomy did not undergo operation, while 35 of the patients randomized
      to observation later had their gallbladders removed. The cumulative risk of
      having a cholecystectomy seemed to level off after 4 years. Gallstone-related
      complications occurred in 3 patients in the observation group, 1 in the operation
      group and 5 of 201 excluded patients. After cholecystectomy, 16 of 222 patients
      had a major complication and 10 a minor. CONCLUSIONS: We found that non-operative
      expectant treatment carries a low risk of complications. Patients should be
      informed that watchful waiting is a safe option.

PMID- 12190100
TI  - Interferon alfa-2b alone or combined with recombinant granulocyte-macrophage
      colony-stimulating factor as treatment of chronic hepatitis C.
AB  - BACKGROUND: To compare the effect of combination therapy with interferon-alpha
      (INF-alpha) and granulocyte-macrophage colony-stimulating factor (GM-CSF) to
      monotherapy with INF-alpha in patients with chronic hepatitis C infection.
      METHODS: Forty-five consecutive patients with chronic hepatitis C, all presenting
      with elevated serum alanine aminotransferases and viremia, were randomized to
      receive either 1) INF-alpha + GM-CSF for 3 months followed by INF-alpha alone for
      9 months (n = 23) or 2) INF-alpha for 12 months (n = 22). Both drugs were
      administered 3 times weekly in doses of 3 mU (INF-alpha) and 50-100 microg
      depending on body weight (GM-CSF). RESULTS: At baseline, there was no difference
      between the treatment groups in terms of age, sex, ALT level, viral load,
      genotype or histological activity and fibrosis in a pretreatment liver biopsy.
      After 12 months' treatment, more patients treated with GM-CSF+ INF-alpha compared
      to patients receiving monotherapy had normalized ALT, 65% and 32%, respectively
      (P = 0.03), but there was no difference in percentages of patients with viral
      clearance between the 2 groups, 48% and 32%, respectively (P = 0.27). At 6
      months' follow-up, the biochemical response had declined to 35% in the
      combination therapy group and to 23% in the monotherapy group (P = 0.37); viral
      clearance had declined to 22% and 27%, respectively (P = 0.67), and the overall
      sustained response rate was 22% and 23%, respectively (P = 1.00). CONCLUSIONS:
      Even though patients receiving INF-alpha + GM-CSF had a significant better
      biochemical response during treatment compared to patients receiving monotherapy,
      the sustained biochemical and virological response was not increased. Thus, GM
      CSF hardly plays any role in the future treatment of chronic hepatitis C.

PMID- 12190101
TI  - Splanchnic and pancreatic tissue perfusion in experimental acute pancreatitis.
AB  - BACKGROUND: Gut hypoperfusion has a major role in the pathogenesis of multiple
      organ failure, which is the main cause of death in severe acute pancreatitis. The
      effects of experimental acute pancreatitis on splanchnic and pancreatic perfusion
      and oxygenation were studied to find out whether gut hypoperfusion occurs already
      at the same time as changes in pancreatic perfusion. METHODS: Twenty-four
      domestic pigs weighing 21-27 kg were randomized to severe or mild acute
      pancreatitis or control groups. Eight anaesthetized and mechanically ventilated
      pigs were intraductally infused with taurocholic acid to induce severe acute
      pancreatitis and eight received intraductal saline to induce mild acute
      pancreatitis. Eight pigs served as controls. RESULTS: Intraductally infused
      taurocholic acid rapidly induced severe necrotizing acute pancreatitis as
      assessed macroscopically and histologically. Histological changes of mild acute
      pancreatitis were seen in animals after intraductal saline infusion. After the
      induction, pancreatic tissue oxygen tension decreased promptly in severe acute
      pancreatitis and increased in mild acute pancreatitis. Laser-Doppler red cell
      flux decreased in severe acute pancreatitis. Gut pH gap and pCO2 gap decreased in
      2 h after the induction of severe acute pancreatitis. Central haemodynamics were
      fairly stable throughout the study period in all groups. CONCLUSION: In
      experimental severe acute pancreatitis, splanchnic malperfusion seems to begin
      with pancreatic hypoperfusion before disturbances in gut microcirculation.

PMID- 12190102
TI  - Continuous evaluation of patient satisfaction in endoscopy centres.
AB  - BACKGROUND: A randomized sample of 14,000 men and women, aged 55-64 years,
      resident in the City of Oslo and Telemark County, were drawn from the population
      registry to be offered a flexible sigmoidoscopy (FS) screening examination. A
      questionnaire was designed to modify routines and evaluate patient satisfaction.
      METHODS: Consecutive participants (4956) were given a questionnaire immediately
      after the FS to be filled in and returned by mail on the following day.
      Participants were asked questions about service, practical issues, and the level
      of pain during the FS and post-examination discomfort. They were also encouraged
      to give their comments in free text. RESULTS: Questionnaire replies were received
      from 4574 (92%) out of 4956 participants. The vast majority reported to have
      experienced no (70%) or slight (21%) pain during the examination. Women reported
      pain and post-examination discomfort more often than men. Pain was also
      associated with age of the patient and length of bowel examined, but not with
      total examination time. The proportion of painless examinations varied between
      endoscopists from 62% to 81%. For all endoscopists collectively, this improved
      during the study period, irrespective of past experience, but trainees seemed to
      adopt the score of their masters. CONCLUSIONS: The study demonstrated that the
      use of feedback information in an endoscopy screening unit may be useful in
      improving standards, including the performance of endoscopists. It is possible
      that the introduction of similar feedback systems in routine endoscopy
      laboratories may in the long run improve the reputation of gastrointestinal
      endoscopy.

PMID- 12190103
TI  - Accuracy of endoscopic ultrasonography in upper gastrointestinal submucosal
      lesions: a prospective multicenter study.
AB  - BACKGROUND: Endoscopic ultrasonography (EUS) is commonly agreed to be the best
      imaging method for diagnosing and differentiating between submucosal lesions in
      the gastrointestinal tract. However, most of the current evidence for this
      derives from retrospective multicenter studies. A prospective multicenter
      analysis of the performance of EUS in diagnosing submucosal lesions in everyday
      practice was therefore conducted. METHODS: Over a 2-year period, this study
      included 150 patients (52% men, mean age 59.8 years) from 23 centers who had a
      presumptive diagnosis of a submucosal lesion on upper gastrointestinal endoscopy.
      The patients' symptoms and EUS results were recorded. Endoscopic and
      endosonographic findings regarding lesion size, layer of origin, and the
      presumptive diagnosis (benign or malignant) were recorded. The reference methods
      used were surgery, biopsy, other imaging tests, and a follow-up period of 6
      months. RESULTS: Of the 150 patients, 102 had an intramural lesion (84 tumors, 18
      other lesions such as cysts, aberrant pancreas, etc.), and 48 had an extraluminal
      compression--in most cases (n = 35) by normal organs or structures. For
      differentiating between a submucosal and an extraluminal compression, the
      sensitivity and specificity of endoscopy were 87% and 29%, whereas those of EUS
      were 92% and 100%. However, the sensitivity and specificity of EUS for
      differentiating between malignant and benign submucosal tumors were only 64% and
      80%, respectively. CONCLUSIONS: The accuracy of EUS in differentiating between
      submucosal tumors and extraluminal compressions is substantially superior to that
      of endoscopy, but EUS is still inadequate for differential diagnosis between
      benign and malignant submucosal tumors. However, EUS is still the best method of
      visualizing submucosal lesions precisely. The influence of EUS on the further
      management in these patients remains to be examined in subsequent studies.

PMID- 12190104
TI  - Favorable response to infliximab treatment in a patient with active Crohn disease
      and pyoderma gangrenosum.
AB  - Pyoderma gangrenosum is an extraintestinal manifestation of inflammatory bowel
      disease requiring meticulous medical and/or surgical treatment. We describe a 46
      year-old patient who developed harsh pyoderma gangrenosum during a severe flare
      up of the underlying Crohn disease of the terminal ileum. The patient responded
      favorably to treatment with infliximab-the chimeric antibody against tumor
      necrosis factor-alpha. The drug was administered intravenously at a dose 5
      mg/kg/BW at baseline and weeks 2 and 6. Abdominal signs and symptoms as well as
      the skin lesions improved markedly before the second infusion. The patient is
      presently on infliximab maintenance regimen at a dose of 5 mg/kg/BW being
      administered as a 3 dose loading regimen at 0, 2 and 6 weeks with a treatment
      free interval of 10 weeks until the next loading dose. The skin lesions remained
      in remission. Infliximab is a promising therapeutic modality for patients with
      Crohn disease and pyoderma gangrenosum.

PMID- 12190105
TI  - Successful endoscopic haemoclipping in Mallory-Weiss syndrome with concurrent
      closure of oesophageal perforation: further prospective evaluation of the
      technique is required.

PMID- 12190106
TI  - Tissue transglutaminase and endomysial antibodies in children with coeliac
      disease.

PMID- 12190107
TI  - Effect of cyclosporin A treatment on renal calcium oxalate binding in
      experimental hyperoxaluria.
AB  - This study was aimed to investigate the effect ofCyclosporin A administration on
      renal calcium oxalate binding under hyperoxaluric condition. Cyclosporin A
      administration or ammonium oxalate treatment increased calcium oxalate binding,
      which was further increased in kidney treated with cyclosporin A and ammonium
      oxalate together. The increase of calcium oxalate binding was associated with
      lipid peroxidation as well as with a concomitant decrease in total thiol in both
      rat and human kdiney homogenate. Cyclosporin A administration to hyperoxaluric
      rats resulted with increased calcium oxalate binding protein. However there was
      no change with specific activity of the protein. In conclusion, Cyclosporin A
      administration either to normal or hyperoxaluric rats is resulted with increased
      concentration of calcium oxalate binding protein as well as enhanced activity due
      to membrane lipid peroxidation.

PMID- 12190108
TI  - Norepinephrine regulates the in vivo expression of the L-type calcium channel.
AB  - The alpha1c subunit (DHP receptor) of the L-type Ca2+ channel is important for
      calcium homeostasis in cardiac muscle. The DHPr provides the primary mechanism
      for calcium influx during contraction. Published results demonstrate three in
      vitro signaling pathways that are important in the regulation of DHPr gene
      expression in neonatal cardiac myocytes, the protein kinase A (PKA), protein
      kinase C (PKC) pathways, and intracellular calcium. To determine whether these
      pathways are important in vivo, we treated adult rats with infusions of
      isoproterenol, or norepinephrine at 200 microg/kg/h and assessed DHPr mRNA and
      protein levels. Following a 3-day infusion isoproterenol (ISO) and norepinephrine
      (NE) produced a small but insignificant reduction in DHPr mRNA levels. When the
      infusions were continued for 7 days isoproterenol increased DHPr mRNA
      accumulation to control levels while NE stimulated a 35% increase in DHPr mRNA
      levels and a 35% increase in protein abundance when compared to controls (p <
      0.05). Furthermore, contractility and Ca2+ transient measurements of isolated
      cardiac myocytes from NE infused animals also display shortened duration of
      contraction/relaxation and increased intracellular free Ca2+ (DFFI) in response
      to electrical stimulation (p < 0.01). We conclude norepinephrine treatment alters
      DHPr mRNA and protein levels, and augments excitation-contraction coupling, and
      thus may be important for modulating cardiac calcium homeostasis in vivo.

PMID- 12190109
TI  - Differential effects of des IGF-1 on Erks, AKT-1 and P70 S6K activation in mouse
      skeletal and cardiac muscle.
AB  - Alterations in the degree of the phosphorylation of ERKI/2, Akt-1 and p70 S6K in
      mouse skeletal and cardiac muscle was examined in vivo following an
      intraperitoneal injection of des IGF-I. Plasma levels of insulin, IGF-I and
      glucose were measured. The administration of des IGF-I had no effect on plasma
      levels of insulin, or IGF-I, but plasma glucose levels were decreased about 50%
      (p < 0.01). In both skeletal and cardiac muscle, des IGF-I increased the
      phosphorylation of Akt-1 at Ser 473 (p < 0.01) with no change in the
      phosphorylation of p44 and p42 MAP kinases at Thr202/Tyr204. The phosphorylation
      of p70 S6K at Thr421/Ser424 was increased in skeletal muscle (p < 0.01), but not
      in cardiac muscle. The phosphorylation of the nuclear transcription factor CREB
      phosphorylation at Ser 133 was not significantly changed in either skeletal or
      cardiac muscle. Des IGF-I increased the phosphorylation of the transcription
      factor FKHR in cardiac muscle only (p < 0.05). These data demonstrate that the
      administration of des IGF-I had differential effects on the activation of the MAP
      kinase and PI 3-kinase pathways in mouse skeletal and cardiac muscle.

PMID- 12190110
TI  - Oral treatment with vanadium of Zucker fatty rats activates muscle glycogen
      synthesis and insulin-stimulated protein phosphatase-1 activity.
AB  - Since the glucose-lowering effects of vanadium could be related to increased
      muscle glycogen synthesis, we examined the in vivo effects of vanadium and
      insulin treatment on glycogen synthase (GS) activation in Zucker fatty rats. The
      GS fractional activity (GSFA), protein phosphatase-1 (PP1), and glycogen synthase
      kinase-3 (GSK-3) activity were determined in fatty and lean rats following
      treatment with bis(maltolato)oxovanadium(IV) (BMOV) for 3 weeks (0.2 mmol/kg/day)
      administered in drinking water. Skeletal muscle was freeze-clamped before or
      following an insulin injection (5 U/kg i.v.). In both lean and fatty rats, muscle
      GSFA was significantly increased at 15 min following insulin stimulation.
      Vanadium treatment resulted in decreased insulin levels and improved insulin
      sensitivity in the fatty rats. Interestingly, this treatment stimulated muscle
      GSFA by 2-fold (p < 0.05) and increased insulin-stimulated PP1 activity by 77% (p
      < 0.05) in the fatty rats as compared to untreated rats. Insulin resistance,
      vanadium and insulin in vivo treatment did not affect muscle GSK-3beta activity
      in either fatty or lean rats. Therefore, an impaired insulin sensitivity in the
      Zucker fatty rats was improved following vanadium treatment, resulting in an
      enhanced muscle glucose metabolism through increased GS and insulin-stimulated
      PPI activity.

PMID- 12190111
TI  - Activation of Raf-1/MEK-1/2/p42/44(MAPK) cascade alone is sufficient to uncouple
      LDL receptor expression from cell growth.
AB  - Our previous observation that induction of low density lipoprotein (LDL) receptor
      expression by a variety of extracellular signals is blocked by PD98059, a
      specific mitogen-activated protein kinase kinase inhibitor, led to the suggestion
      that the growth-responsive p42/44(MAPK) cascade plays a critical role in
      regulating LDL receptor transcription. To analyze the specific contribution of
      the p42/44(MAPK) cascade in regulating cell growth and LDL receptor induction, we
      established a HepG2-derived cell line that stably expresses an inducible form of
      oncogenic human Raf-1 kinase. Using this system, we provide direct evidence that
      specific activation of this cascade alone is not only required but is sufficient
      to fully induce LDL receptor expression. Interestingly, degree of p42/44(MAPK)
      activation determines the extent of LDL receptor induction. However, activation
      of p42/44(MAPK) in the above cells led to the inhibition of DNA synthesis, caused
      growth arrest, decrease in cyclin A and upregulation of p21(Cip) expression in a
      time-dependent manner. These results suggest that each of these two processes can
      be regulated independently of each other in response to p42/44(MAPK) activation.
      Thus, extent of p42/44(MAPK) activation may be important in transducing divergent
      cellular responses in human cells with implications for altered signaling
      resulting in hypercholesterolemia.

PMID- 12190112
TI  - Effect of dietary fibres on constituents of complex carbohydrates in
      streptozotocin induced diabetic rat tissues.
AB  - The effect of dietary fibres on constituents of complex carbohydrates in various
      tissues of streptozotocin induced diabetic rats is presented by analysing
      different constituents of complex carbohydrates in presence and absence of
      dietary fibre. Wheat bran was effective in preventing the decrease (14%) in total
      sugars in spleen and an increase in total sugars in stomach (33%) during
      diabetes. Decrease in uronic acid content during diabetes in spleen was prevented
      to the extent of 25% by the presence of wheat bran in the diet. The other
      parameters which were affected by the presence of wheat bran in the diet during
      diabetes are amino sugar (brain and stomach), sulphates (liver) and protein
      (lungs and stomach). Guar gum was effective in preventing the decrease in total
      sugar content in spleen by 28% and sulphate content in liver by 14% during
      diabetes. Variation in protein content in lungs was observed in diabetes. The
      results indicated beneficial role of dietary fibres like wheat bran and guar gum
      on complex carbohydrates to varying extents in different tissues.

PMID- 12190113
TI  - Differential expression of GAPDH and beta3-actin in growing collateral arteries.
AB  - Housekeeping genes like glyceraldehyde-3-phosphate dehydrogenase (GAPDH) and beta
      actin are often used as internal standards for quantitative RNA analysis. In our
      study we analyzed the relative expression level of GAPDH and beta-actin as well
      as of the 18S rRNA and the Poly (A)+ RNA in growing collateral arteries in a
      rabbit model of arteriogenesis which is not associated with ischemia. Relative
      quantitation of the housekeeping genes displayed a significant upregulation of
      the beta-actin- and GAPDH mRNA during the first 24 h of vessel growth. For day 3
      our results revealed an even stronger upregulation of the beta-actin mRNA (140%)
      but a significant downregulation of the GAPDH mRNA (50% of control). The 18S
      rRNA, however, showed for the same periods only minor alterations compared to the
      Poly (A)+ RNA. From these results we conclude that the 18S rRNA, but not the
      GAPDH- or beta-actin mRNA is an appropriate internal control for relative
      quantitation of gene expression under conditions of cell proliferation in growing
      vessels.

PMID- 12190114
TI  - Stretch-induced paracrine hypertrophic stimuli increase TGF-beta1 expression in
      cardiomyocytes.
AB  - Cardiac hypertrophy refers to the abnormal growth of cardiomyocytes, and is often
      caused by valvular heart disease and hypertension. It involves the activation of
      growth, including increased protein synthesis and changes in gene expression.
      Transforming growth factor-beta1 (TGF-beta1) may play a central role in
      protecting the heart during the hypertrophic response by helping to restore
      normal functions of the affected myocardium. We tested the hypothesis that
      cardiomyocytes respond to stretch-induced paracrine hypertrophic stimuli with
      increased expression of TGF-beta1. To that purpose, we investigated whether
      angiotensin II (All), endothelin- I (ET-1) and TGF-beta, secreted by stretched
      cardiac and vascular cells, are involved in the paracrine mechanisms of stretch
      induced changes of TGF-beta1 mRNA expression in stationary (i.e. non-stretched)
      cardiomyocytes. Our results indicated that TGF-beta1 mRNA expression in
      stationary cardiomyocytes was increased by AII release from cardiomyocytes that
      had been stretched for 30-60 min. Furthermore, it is likely that ET-1 and TGF
      beta were released by stretched cardiac fibroblasts and endothelial cells to
      induce TGF-beta1 mRNA expression in stationary cardiomyocytes. Stretched vascular
      smooth muscle cells did not influence TGF-beta1 mRNA expression in stationary
      cardiomyocytes. These results indicate that AII, ET-I and TGF-beta, released by
      cardiac cell types, act as paracrine mediators of TGF-beta1 mRNA expression in
      cardiomyocytes. Therefore, we conclude that in stretched myocardium the
      cardiomyocytes, cardiac fibroblasts and endothelial cells take part in
      intercellular interactions contributing to cardiomyocyte hypertrophy.

PMID- 12190115
TI  - Integrity of erythrocytes of hypercholesterolemic rats during spices treatment.
AB  - In rats rendered hypercholesterolemic by maintaining them on a cholesterol
      enriched diet (0.5%) for 8 weeks, inclusion of spice principles--curcumin (0.2%)
      or capsaicin (0.015%) or the spice--garlic powder (2.0%) in the diet, produced
      the expected hypolipidemic effect. Plasma cholesterol which was more than 200%
      that of basal control in hypercholesterolemic rats, was decreased by these
      dietary spice principles and garlic by 25-39%. Erythrocyte membranes of
      hypercholesterolemic rats were relatively enriched in cholesterol, which was
      about 120% of basal control, while membrane phospholipid was unaffected. This
      resulted in a significant alteration in cholesterol to phospholipid ratio of RBC
      membranes. Dietary curcumin, capsaicin and garlic were observed to counter this
      altered lipid profile of erythrocyte membranes in hypercholesterolemic situation
      by producing a significant 10-14% decrease in membrane cholesterol content. As a
      result of alteration in membrane structural lipids, the structural integrity of
      RBCs was also affected. An examination of the osmotic fragility of erythrocytes
      in various groups, indicated that RBCs of hypercholesterolemic rats were
      relatively fragile compared to normal controls. Dietary curcumin, capsaicin and
      garlic appeared to correct this increased fragility of erythrocytes.

PMID- 12190116
TI  - Insulin restores expression of adenosine kinase in streptozotocin-induced
      diabetes mellitus rats.
AB  - The activity of adenosine kinase is significantly impaired in tissues of diabetic
      rat. Changes in the activity of adenosine kinase were accompanied by alterations
      in its mRNA and protein level. These changes depended on insulin level and were
      not related to glucose level. During the first 7 h after insulin treatment the
      level of adenosine kinase mRNA, protein and enzymatic activity in kidneys, liver
      and heart returned to normal values. The observed relation between insulin and
      adenosine kinase expression level may suggest that insulin increases the rate of
      adenosine kinase gene transcription. Decreased activity of adenosine kinase was
      associated with elevated level of adenosine in diabetic tissues. On the 10th day
      after the STZ treatment there was a 3.5 and 2-fold increase in adenosine content
      in heart and liver, respectively. On the other hand, in diabetic kidney adenosine
      level was elevated only by 20%. Administration of insulin to diabetic rats
      resulted in a drop of adenosine to the level seen in normal heart and liver
      whereas, in kidneys the adenosine content was 50% lower than that observed under
      normal conditions. The time-dependent coarse of changes in adenosine level was
      different from that observed for adenosine kinase activity, what may suggest that
      other factors, possibly nucleoside transporters are also important for
      controlling adenosine level in the cell.

PMID- 12190117
TI  - Protective effect of green tea extract against the erythrocytic oxidative stress
      injury during mycobacterium tuberculosis infection in mice.
AB  - The present study has been undertaken to monitor the extent of oxidative stress
      in mice infected with M tuberculosis and the role of crude green tea extract in
      repairing the oxidative damage. The mice were divided into three groups of 9
      each; normal, infected-untreated and infected-treated. The infected group of
      animals exhibited significant enhancement of erythrocytic catalase and
      glutathione peroxidase activities along with elevated levels of erythrocytic
      total thiols and plasma lipid peroxidation as compared to normal animals. The
      infected group also exhibited significantly decreased activity of superoxide
      dismutase and levels of glutathione in erythrocytes. Upon oral administration of
      green tea extract for seven days the oxidative stress parameters were reverted
      back to near normal levels as evidenced by a fall in catalase, glutathione
      peroxidase, total thiol and extent of lipid peroxidation with concomitant
      increase in the levels of SOD and reduced glutathione in infected animals. The
      findings thus, portray that there is a high oxidative stress during early stages
      of tuberculosis and antioxidants such as green tea extract, can play a vital role
      by reducing stress through adjuvant therapy.

PMID- 12190118
TI  - Characterization of the in vitro kinase activity of a partially purified soluble
      GST/JAK2 fusion protein.
AB  - The biochemical and biophysical characteristics of Janus protein-tyrosine kinases
      (JAKs), which are essential early mediators of cytokine-initiated signal
      propagation, are virtually undefined. To facilitate the in vitro analysis of JAK
      mediated catalysis, we substantially purified a soluble recombinant JAK2 and
      developed a novel means of quantifying JAK-catalyzed product formation.
      Glutathione-S-transferase fusion proteins containing active and inactive forms of
      rat Janus kinase 2 (GST:rJAK2 and GST:rJAK2(CA795)) were highly purified via
      affinity chromatography. A microtiterplate-based ELISA was used to measure
      tyrosine phosphorylation of a streptavidin-immobilized biotinylated STAT1-derived
      peptide. The ELISA data indicated that only about 1% of the enzyme was involved
      in exogenous substrate phosphorylation. Other immobilized peptides served as
      apparent substrates with varying efficacy. Traditional radioisotopic autokinase
      assays demonstrated that the activity of the purified fusion protein was
      inhibited by a variety of tyrphostin inhibitors. Non-radiolabeled adenine
      nucleotides, but not guanine nucleotides, inhibited the radioisotopic autokinase
      assay. These observations verify that the catalytic activity of JAK2 is highly
      regulated, and are consistent with the suggestion that JAK2 may require
      additional accessory proteins, such as a potential upstream regulatory kinase,
      for full catalytic activity.

PMID- 12190119
TI  - Regulation of mitochondrial contact sites in neonatal, juvenile and diabetic
      hearts.
AB  - Mitochondrial contact sites (MiCS) are dynamic structures involved in high
      capacity transport of energy from mitochondria into the cytosole. Previous
      studies revealed that in normal conditions the actual number of MiCS is in
      correlation with the energy requirements of the heart, particularly with those
      for its contractile work. Although the detailed mechanisms of signalling between
      the processes of energy utilisation and MiCS formation in the heart are not yet
      elucidated, it is known that intracellular Ca2+ transients are intimately
      involved in this crosstalk. The present study is devoted to investigation of Ca2+
      linked MiCS formation in healthy adult hearts and in hearts with modified Ca2+
      handling such as in developing, in juvenile and diabetic myocardium. Experiments
      were performed on hearts of healthy rats on the 22nd embryonal day, 1st, 4th, 7th
      and 14th postnatal days as well as on adult hearts. Diabetic hearts were
      investigated on the 8th day after streptozotocin injection (45 mg x kg(-1) iv.)
      to adult rats. Intracellular Ca2+ movements were affected by modulation of Ca2+
      concentration in perfusion solution (1.6 or 2.2 mmol l(-1) in isolated,
      Langendorff-perfused hearts, by calcium paradox (CaP) or by replacing of Ca2+ by
      Cd2+ ions. Elevation of extracellular Ca2+ was reflected by 30.1, 10.4 and 24.1%
      increase in intracellular free Ca2+ concentration in healthy adult, diabetic and
      14-day old hearts respectively. In developing hearts the amount of MiCS was
      culminating on the 4th postnatal day. In adult hearts, elevated calcium in the
      perfusion solution, CaP as well as diabetes led to a significant increase in the
      amounts of MiCS formed (58.1, 77.2 and 86.5% respectively; p < 0.05). Diabetic
      and 14-day old hearts naturally exhibited amounts of MiCS comparable to those
      obtained by Ca2+-stimulation of MiCS formation in adult healthy hearts. In
      contrast to healthy controls, perfusion of diabetic and 14-day old hearts with
      elevated Ca2+ as well as induction of CaP exerted little influence on MiCS
      formation (4.4 and 8.2% for elevated Ca2+; 2.9 and 10.7% for CaP; p > 0.05). A
      replacement of Ca2+ by Cd2+ ions lowered the amount of MiCS in healthy adult and
      diabetic hearts (61 and 52.2%; p < 0.05). In conclusion, during development, the
      formation of MiCS may be influenced by both, permanent stimulation by Ca2+
      signalling and the availability of mCPK. In healthy adult hearts the amount of
      MiCS is modulated by intracellular Ca2+ transients in response to changes in
      extracellular Ca2+ concentration. In diabetic hearts the modulation of MiCS
      formation is naturally attenuated, apparently as a consequence of persisting
      alterations in Ca2+-handling.

PMID- 12190120
TI  - Occurrence of histone H1 degrees protein in rat alveolar macrophages.
AB  - Histone H1 of rat alveolar macrophages, neutrophilic granulocytes and monocytes
      extracted with 5% (v/v) perchloric acid was studied in order to see whether a
      protein similar to histone H1 degrees of rat liver exists in these specialized
      cells. The biochemical methods used involved SDS and acid-urea polyacrylamide gel
      electrophoresis, gel filtration on BioGel P100 and raising antisera against
      chromatographically purified rat liver H1 degrees and histone H1. The antiserum
      was applied for further characterization of the presumptive H1 degrees fraction
      using ELISA and Western blot analysis. The results from our studies showed that
      histone H1 degrees protein is present in rat alveolar macrophages, monocytes and
      neutrophilic granulocytes, but its quantity in neutrophilic granulocytes is very
      much less than macrophages and monocytes.

PMID- 12190121
TI  - Ischemic shortening of action potential duration as a result of KATP channel
      opening attenuates myocardial stunning by reducing calcium influx.
AB  - Action potential duration (APD) shortening due to opening of sarcolemmal ATP
      dependent potassium (KATP) channels has been postulated to protect the myocardium
      against postischemic damage by reducing Ca2+ influx. This hypothesis was
      assessed, assuming that increased postischemic stunning due to KATP channel
      inhibition with glibenclamide could be reverted by the addition of the Ca2+
      channel blocker diltiazem. Percent wall thickening fraction (%WTh, conscious
      sheep) and APD (open-chest sheep) were obtained from the following groups:
      control: 12 min ischemia by anterior descending coronary artery occlusion
      followed by 2 h reperfusion; glibenclamide: same as control, with glibenclamide
      (0.4 mg/kg) infused 30 min before ischemia; diltiazem: same as control, with
      diltiazem (100 microg/kg) administered prior to ischemia;
      glibenclamide+diltiazem: both drugs infused as in glibenclamide and diltiazem
      groups. APD was reduced in control ischemia. Conversely, KATP-channel blockade by
      glibenclamide lengthened APD and increased postischemic stunning (p < 0.01 vs.
      control); glibenclamide+diltiazem did not shorten APD but enhanced functional
      recovery (p < 0.01 vs. glibenclamide). Ca2+ channel blockade improvement of
      increased stunning provoked by KATP channel inhibition supports the hypothesis
      that APD shortening due to opening of KATP channels protects against postischemic
      stunning by limiting Ca2+ influx.

PMID- 12190122
TI  - Stereo-isomer specific induction of renal cell apoptosis by synthetic muramyl
      dipeptide (N-acetylmuramyl-L-alanyl-D-isoglutamine).
AB  - The cytotoxicity of bacterial cell wall components, muramyl dipeptide (synthetic
      N-acetylmuramyl-L-alanyl-D-isoglutamine; L,D-MDP) and lipopolysaccharide (LPS),
      was investigated in several kidney cell lines. MDP and LPS were toxic to rabbit
      and monkey kidney cells, MDP was toxic to canine kidney cells, but not to human
      or porcine kidney cells. Notably, L,D-MDP was >100-fold more cytotoxic/microg
      than the D,D-MDP and L,L-MDP, as well as LPS. L,D-MDP and analogs containing L,D
      MDP were the most widely cytotoxic of the MDP tested. The MDP-induced
      cytotoxicity was characterized as apoptosis by DAPI staining and DNA laddering.
      The acute rabbit kidney (RK13) cell apoptosis (cell death in < 5 h) induced by
      apical or basal application of MDP was associated with glutamate (Glu) release,
      decreased gamma-glutamyltranspeptidase (GGT) and acidosis and was suppressed by
      Indomethacin, Naproxen and Curcumin. The cytotoxic activity of L,D-MDP was
      decreased significantly by 24 h incubation in human sera. Aged (> 2 year-old)
      rabbits that apparently failed to quickly clear and excrete a uveitogenic dose of
      MDP within 24 h died in I week. The results indicate that minute amounts (5
      ng/ml) of MDP containing L-alanyl-D-isoglutamine can induce renal cell apoptosis
      in vitro and support MDP-induced kidney cytotoxicity in rabbits. Also, the
      results indicate that MDP in sera can be detected utilizing the RK13 cell
      bioassay and that failure to rapidly clear and excrete L,D-MDP is associated with
      uveitis and death in aged rabbits.

PMID- 12190123
TI  - Alterations in antioxidant enzymes and oxidative damage in experimental diabetic
      rat tissues: effect of vanadate and fenugreek (Trigonellafoenum graecum).
AB  - With the premise that oxygen free radicals may be responsible for the severity
      and complications of diabetes, the level of antioxidant enzymes catalase (CAT),
      superoxide dismutase (SOD) and glutathione peroxidase (GPx) as well as the
      oxidative damage were examined in the tissues of control, diabetic and treated
      rats. After 3 weeks of diabetes, the activity of CAT was significantly increased
      in heart in diabetes (about 6-fold) but decreased in liver. The SOD activity
      decreased significantly in liver but increased in brain. The activity of GPx
      decreased significantly in liver and increased in kidney. A significant increase
      was observed in oxidative damage in heart and kidney and a small increase in
      brain with decrease in liver and muscle. Vanadate and fenugreek (Trigonella
      foenum graecum) administration to diabetic animals showed a reversal of the
      disturbed antioxidant levels and peroxidative damage. Results suggest that
      oxidative stress play a key role in the complications of diabetes. Vanadate and
      fenugreek seeds showed an encouraging antioxidant property and can be valuable
      candidates in the treatment of the reversal of the complications of diabetes.

PMID- 12190124
TI  - Downregulation of PTEN/MMAC/TEP1 expression in human prostate cancer cell line
      DU145 by growth stimuli.
AB  - Genetic alterations and/or deletion of the tumor suppressor gene PTEN/MMAC/TEP1
      occur in many types of human cancer including prostate cancer. We describe the
      production of monoclonal antibody against recombinant human PTEN and the study of
      PTEN gene and protein expression in three commercially available human prostate
      cancer cell lines, PC-3, LNCaP, and DU 145. Northern blotting analyses showed
      that LNCaP and DU145 but not PC-3 cells expressed PTEN mRNA. However, Western
      blotting analyses using a monoclonal antibody against PTEN demonstrated the
      expression of PTEN protein in DU145 but not LNCaP cells. In DU 145 cells, PTEN
      expression at both the mRNA and protein levels inversely correlated with serum
      concentrations and levels of PKB/Akt phosphorylation. In addition, the basal
      activity of PKB/Akt as indicated by level of phosphorylation was higher in
      prostate cancer cells which do not express PTEN than that in the cells expressing
      wild type PTEN. Thus, PTEN may play a critical role in regulating cellular
      signaling in prostate cancer cells.

PMID- 12190127
TI  - Endoscopy-assisted open treatment of condylar fractures of the mandible:
      extraoral vs intraoral approach.
AB  - By using an endoscopy assisted extraoral and transoral approach for open
      reduction of condylar mandible fractures with limited incisions, the risk of
      facial nerve damage and extensive visible scars can be reduced. The endoscopy
      assisted treatment of 17 consecutive patients with fractures of the condyle was
      performed from April 1998 to December 1999. Of the 17 patients, 13 presented with
      additional mandibular fractures. Nine of the 17 patients were treated by a
      submandibular approach and eight by a transoral approach. Adequate anatomic
      reduction was achieved by the submandibular and transoral approach using an
      endoscopy-assisted technique. The transoral approach proved to be a reliable
      surgical approach for fractures of the mandibular condyle, even when dislocation
      with lateral override was present. In four patients, angulated drills and
      screwdrivers facilitated the transoral treatment of condylar fractures.
      Transbuccal stab incisions and the use of trochars were not needed in these four
      patients. The extraoral approach was indicated for severely dislocated fractures
      such as fractures with medial override or comminution.

PMID- 12190125
TI  - Comparison of the antisecretory and antiulcer activity of epidermal growth
      factor, urogastrone and transforming growth factor alpha and its derivative in
      rodents in vivo.
AB  - This study investigates the effects of epidermal growth factor (EGF), urogastrone
      (UG) and transforming growth factor-alpha (TGFalpha) and its derivative on
      dimaprit- and pentagastrin-induced gastric acid secretion and on acidified
      ethanol (AE)-evoked ulcer formation in anaesthetized rats. EGF, TGFalpha and UG
      administered subcutaneously (s.c.) 30 min before dimaprit inhibited gastric acid
      secretion. Against pentagastrin-stimulated secretion, TGFalpha inhibited, while
      EGF and UG potentiated, acid secretion dose-dependently. Intraduodenal (i.d.)
      administration of TGFalpha and UG had no effect, while EGF potentiated, both
      secretagogue-induced acid secretion in the same dosage schedule. Administration
      of either EGF, UG or TGFalpha i.v. bolus, in response to continuous infusion of
      dimaprit resulted in a significant (p < 0.05-p < 0.001) inhibition of acid
      secretion which was transient and returned to normal within 30-45 min for UG
      while it slowly returned to normal for EGF and TGFalpha. The truncated form of
      TGFa (amino acids 34-43) did not show any antisecretory effect when administered
      parenterally. Acidified ethanol produced gastric haemorrhagic lesions in the rat
      1 h after oral administration. The gastric mucosal protective effects of
      TGFalpha, EGF and UG administered either orally or s.c. 30 min before the
      administration of AE were dose-dependent against this model of ulcer induction.
      Indomethacin (Indo), administered 15 min before AE to inhibit prostanoids
      biosynthesis, significantly (p < 0.001) reduced the cytoprotective effects of
      TGFalpha, EGF and UG and aggravated the ulcer index when administered s.c. The
      results show that PGs may be involved in mediating the protective effects of the
      three growth factors. Administration of NG-nitro-L argininemethylester (L-NAME)
      15 min prior to TGFa, EGF and UG s.c. or orally, significantly (p < 0.001)
      decreased the degree of ulcer indices and was able to reduce the protective
      effects of TGFalpha, EGF and UG, thus including the role of NO in mediating the
      protective effects of these growth factors. In conclusion, these results have
      demonstrated that EGF, UG and TGFalpha have a short and reversible inhibitory
      effect on dimaprit-stimulated gastric acid secretion and each is effective
      parenterally but not orally. UG and EGF potentiated, while, TGFa inhibited
      pentagastrin-stimulated acid secretion. In addition, TGFalpha seems to lose its
      activity when it is truncated from the C terminus. The present study also
      suggests that EGF, UG and TGFalpha are equally effective against AE-induced
      gastric ulcer and bring about their cytoprotective action through their reduction
      of acid secretion and through PG and NO pathways.

PMID- 12190128
TI  - Identifying the position of an ear from a laser scan: the significance for
      planning rehabilitation.
AB  - Laser scanning techniques are used to plan the construction of prosthetic ears as
      dimensional measurements between anthropometric points can be accurately measured
      on a screen image. The aim of this study was to determine if these techniques
      could be used to assess the position of ears on the face. Computer-generated
      images were created from laser scans of 20 subjects. Frames of reference were
      constructed by locating a series of anthropometric points on the face from which
      three orthogonal planes were constructed. A central reference point was
      identified at the intersection of the three orthogonal planes. Dimensional
      measurements were made between anthropometric points on the ear and the reference
      planes. The differences between anthropometric points and the reference planes on
      the left and right sides of the face were small. It was possible to describe the
      location of points three-dimensionally with respect to a central reference point.
      The development of frames of reference and a central reference point would appear
      to offer many advantages in the assessment and description of ear position for
      patients requiring reconstruction with prostheses.

PMID- 12190126
TI  - Peroxo-bridged divanadate as selective bromide oxidant in bromoperoxidation.
AB  - Diperoxovanadate is effective only in presence of free vanadate in vanadium
      dependent bromoperoxidation at physiological pH. Peroxide in the form of bridged
      divanadate complex (VOOV-type), but not the bidentate form as in
      diperoxovanadate, is proposed to be the oxidant of bromide. In order to obtain
      direct evidence, peroxo-divanadate complexes with glycyl-glycine, glycyl-alanine
      and glycyl-asparagine as heteroligands were synthesized. By elemental analysis
      and spectral studies they were characterized to be triperoxo-divanadates,
      [V2O,(O2)3(peptide)3] x H2O, with the two vanadium atoms bridged by a peroxide
      and a heteroligand. The dipeptide seems to stabilize the peroxo-bridge by inter
      ligand interaction, possibly hydrogen bonding. This is indicated by rapid
      degradation of these compounds on dissolving in water with partial loss of
      peroxide accompanied by release of bubbles of oxygen. The 51V-NMR spectra of such
      solutions showed diperoxovanadate and decavanadate (oligomerized from vanadate)
      as the products. Additional oxygen was released on treating these solutions with
      catalase as expected of residual diperoxovanadate. The solid compounds when added
      to the reaction mixtures showed transient, rapid bromoperoxidation reaction, but
      not oxidation of NADH or inactivation of glucose oxidase, the other two
      activities shown by a mixture of diperoxovanadate and vanadyl. This demonstration
      of peroxide-bridged divanadate as a powerful, selective oxidant of bromide,
      active at physiological pH, should make it a possible candidate of mimic in the
      action of vanadium in bromoperoxidase proteins.

PMID- 12190129
TI  - Inflammatory change in the upper joint space in temporomandibular joint with
      internal derangement on gadolinium-enhanced MR imaging.
AB  - The object of this study was to clarify the relationship between gadopentetate
      dimeglumine (Gd-DTPA) contrast enhancement of the upper joint space and the
      severity of internal derangement of the temporomandibular joint (TMJ). Fifty
      patients with 63 painful TMJs underwent 1.5T MR imaging with T1-weighted images
      before and after an intravenous injection of Gd-DTPA with or without fat
      suppression. The relationship was investigated between the contrast enhancement
      at the upper joint space and disc position, disc morphology or bone morphology.
      Of the 63 joints, a significant contrast enhancement in the upper joint space was
      detected in 32 joints. There was a significant high incidence of anterior disc
      displacement without reduction in the contrast-enhancement positive group
      compared to the negative group (P = 0.021), but there was no significant
      difference for disc morphology (P = 0.094) and bone morphology (P = 0.384). Gd
      DTPA enhanced MR imaging may potentially have diagnostic value for internal
      derangements of TMJs.

PMID- 12190130
TI  - Intraoral minor salivary gland neoplasm: a single institution experience of 80
      cases.
AB  - From March 1991 to February 2001, 80 cases of minor salivary gland tumours were
      diagnosed in the Department of Oral and Maxillofacial Surgery at the University
      of Maryland at Baltimore (Baltimore, MD, USA). Data extracted from a
      retrospective chart review included age, sex, symptoms, site, histological
      diagnosis. treatment and outcome. Pleomorphic adenoma was the most common benign
      tumour and makes up 89.5% of all benign tumours. The percentage of malignancy
      (76.3%) was much higher than that found in other studies. Of the malignant
      tumours, 54.1% were mucoepidermoid carcinomas. This study differs from many
      previous reviews that were published by pathologists rather than a surgical unit.

PMID- 12190131
TI  - Field change and oral cancer: new evidence for widespread carcinogenesis?
AB  - Patients with oral squamous cell carcinoma (OSCC) are at risk of developing
      second or multiple primary cancers as a result of field cancerization in the
      upper aerodigestive tract. In order to quantify the incidence of field change
      observable in oral mucosa, 26 consecutive new (untreated) patients presenting
      with a unilateral OSCC (18) or a premaligant lesion (eight) underwent 'mirror
      image' biopsies from clinically normal-looking mucosa at corresponding anatomical
      sites. A total of 15 patients (58%) demonstrated histologically abnormal tissue
      upon microscopic examination: six showed reactive change/cellular atypia
      associated with chronic irritation, seven exhibited frank dysplasia, whilst two
      displayed carcinoma-in-situ (CIS) or microinvasive SCC. Although not
      statistically significant, there was an observable trend for the lateral/ventral
      tongue and floor of mouth to display increased vulnerability to dysplastic
      change.

PMID- 12190132
TI  - Primary tumour resection of tongue carcinoma based on response to preoperative
      therapy.
AB  - The purpose of this study was to investigate the selection of resection
      techniques for primary lesions of advanced tongue carcinoma based on the
      effectiveness of our current preoperative therapy. Forty-three patients with
      advanced but potentially resectable squamous cell carcinoma of the tongue were
      included in this study. All patients were treated with preoperative concurrent
      chemoradiotherapy followed by conventional surgical resection. Semiserial
      sections of whole surgical specimen of primary lesion were evaluated
      histopathologically. In patients who achieved 85% and above regression, the
      extent of residual tumours two-dimensionally and in the deep layers was lesser,
      and the rate of tumour cell survival was lower, than in other patients.
      Furthermore, residual tumours tended to be localized to the superficial layers in
      the centre. These findings suggest that even in advanced tongue carcinomas it is
      possible to avoid extended resection and perform a less invasive surgery in which
      the extent of resection is reduced to preserve morphology and function in
      patients who achieved 65% and above regression following preoperative
      chemoradiotherapy.

PMID- 12190133
TI  - Juvenile intraoral pleomorphic adenoma: report of five cases and review of the
      literature.
AB  - The aim of this study is to report on five cases of intraoral pleomorphic adenoma
      (PA) in patients under 18 years of age and to review the literature. Intraoral
      salivary gland tumours were reviewed in two Brazilian institutions and five cases
      of PA in patients under 18 years of age were found. Clinical data were obtained
      from the medical records and paraffin-embedded tissues were sectioned for
      proliferating cell nuclear antigen (PCNA) and p53 immunohistochemical analysis.
      Four patients were female and one was male; two cases affected the palate, two
      the upper lip and one the tongue. All five patients were treated surgically and
      after long follow-up periods no recurrences were observed. Tumour cells were
      weakly positive for PCNA and negative for p53. PA should be considered in the
      differential diagnosis of submucosal nodules in young patients. In youngsters, PA
      seems to have similar biological characteristics as in adults, with low
      recurrence rates after surgical resection.

PMID- 12190134
TI  - Evaluation of ketorolac (Toradol) with varying amounts of codeine for
      postoperative extraction pain control.
AB  - This study analyzes the combination of oral ketorolac 10 mg with varying amounts
      of codeine phosphate, and the postoperative pain relief that developed from these
      combinations. Five groups of patients were administered the codeine/ketorolac
      combinations. Variations of the combinations were analyzed to ascertain if an
      optimal analgesic ratio existed. All controllable variables involved with the
      surgical procedure were held constant to allow for better evaluation of
      postoperative pain. Results obtained from 67 patients indicated that the best
      pain relief was achieved with a combination of 10 mg ketorolac and 15 mg codeine
      phosphate. Codeine alone provided adequate analgesia, but the addition of
      ketorolac reduced the patients' perceived side effects. The presence of codeine
      in the analgesic combination was also shown to reduce the number of days that the
      patient required the medication postoperatively. Reducing the duration of
      medication use postoperatively may also minimize the possible side effects of
      ketorolac and codeine, which could develop with extended periods of use.

PMID- 12190135
TI  - Mandibular reconstruction: a clinical and radiographic animal study on the use of
      autogenous scaffolds and platelet-rich plasma.
AB  - This paper reports on an experimental animal study evaluating a method of
      mandibular reconstruction. After a successful pilot study, 28 goats underwent a
      continuity resection of the mandibular angle. Primary reconstruction was carried
      out using specially designed osteosynthesis plates and screws. The defect was
      bridged by the original cortical scaffold, filled with an autogenous bone graft
      from the iliac crest. To accelerate bone healing, platelet-rich plasma (PRP) was
      mixed with the particulate bone graft in 14 goats. All goats had uneventful
      healing. The osteosynthesis plates and screws withstood immediate loading for
      periods varying from 3 weeks to 3 months. The use of PRP appeared to enhance bone
      healing considerably.

PMID- 12190136
TI  - Functional reconstruction of the non-human primate mandible using recombinant
      human bone morphogenetic protein-2.
AB  - The purpose of this study was to evaluate the long-term functional properties of
      regenerated bone induced by recombinant human bone morphogenetic protein-2 (rhBMP
      2) in segmental bone defects of primate mandibles. The 30-mm defects were created
      in the mandibles of six young monkeys and the mandibles were fixed with titanium
      plates. Then 9 mg of rhBMP-2 permeating a poly-D, L-lactic-co-glycolic acid
      coated gelatin sponge (PGS) was implanted into the bone defect. Dental implants
      were placed into the regenerated mandible 20 weeks after surgery, then
      suprastructures were placed and masticatory force loading was begun 8 weeks after
      the insertion of the dental implants. Bone formation and the quality of new bone
      were evaluated radiologically and histologically at 15 and 30 weeks after
      surgery, and 4 and 24 weeks after masticatory force loading. The resected
      mandibles were completely regenerated with the rhBMP-2-induced bone. Excellent
      remodelling and consolidation of new bone were observed after loading. This study
      demonstrated that the new bone induced by rhBMP-2 in large segmental defects was
      maintained and functional for at least 1 year. Bone regeneration induced by rhBMP
      2 holds promise as a future therapy and may be an effective alternative to
      autogenous bone grafts for implant dentistry and reconstructive surgery.

PMID- 12190137
TI  - Effects of liquid nitrogen cryotherapy and bone grafting on artificial bone
      defects in minipigs: a preliminary study.
AB  - Liquid nitrogen cryotherapy has been advocated as an adjunct in the enucleation
      and curettage of locally aggressive lesions of the jaws. Simultaneous autogenous
      bone grafting has also been advocated to accelerate bone formation and reduce
      morbidity. There is, however, relatively little scientific basis for either of
      these hypotheses. In this study, nine Yucatan minipigs had artificial defects
      created in the mandible, which were treated with liquid nitrogen spray. Half of
      the defects were grafted with autogenous bone from the chin and half were closed
      primarily. Two animals were sacrificed 3 days postoperatively to measure the
      width of necrosis and the rest were sacrificed at 3 months to assess healing and
      new bone formation. It was found that drilling the artificial defects alone
      caused bone necrosis for a mean depth of 0.09 mm. Liquid nitrogen cryospray
      caused a mean depth of bone necrosis of 0.82 mm (range 0.51-1.52 mm). The defects
      that were bone grafted healed well clinically. Defects not bone grafted showed a
      50% rate of wound breakdown and sequestrum formation with delayed healing. Vital
      staining showed a non-significantly greater rate of bone formation in the grafted
      defects. Digitally superimposed radiography showed a non-significantly greater
      bone density in the non-grafted defects at 3 months postoperatively. It appears
      that liquid nitrogen cryospray does devitalize an area of bone around defects in
      the mandible. The width of necrosis is usually less than 1 mm and subsequent
      healing is enhanced by autogenous bone grafting. This has clinical implications.

PMID- 12190138
TI  - The superficial mandibular gland of the rabbit: a new experimental model for
      scintigraphic evaluation of salivary glands.
AB  - The aim of this study was to provide an appropriate experimental model to study
      functional changes in salivary glands using scintigraphy. Although the rabbit was
      frequently used for laboratory experiments, there are only a few studies that
      describe the exact position of its different salivary glands on the
      sialoscintigram. Twenty rabbits were used for the study; ten of them were
      anatomically dissected to provide the required topographic anatomy on the
      different salivary and lacrimal glands. The remaining ten animals underwent a
      static scintigraphy after extirpation of a particular salivary gland. Changes in
      the pattern of tracer uptake indicated the exact position of every gland allowing
      its evaluation. The results show that the 99mTcO4- uptake can only be selectively
      evaluated in two salivary glands, the superficial mandibular gland and the
      parotid gland. The superficial mandibular gland was proved to be a particularly
      useful model to evaluate functional changes of salivary gland parenchyma due to
      its well defined and high enhanced structure which allows a precise detection and
      measurement of the tracer uptake. Additionally, the good surgical accessibility
      of this gland and the existence of a well defined capsule facilitate associated
      histological studies of its parenchyma.

PMID- 12190139
TI  - Contemporary views on dry socket (alveolar osteitis): a clinical appraisal of
      standardization, aetiopathogenesis and management: a critical review.
AB  - The objective of this article is to harmonize descriptive definitions for the
      condition known as alveolar osteitis and to critically review and discuss the
      aetiology and pathogenesis of alveolar osteitis. In addition, the need for the
      identification and elimination of risk factors as well as the preventive and
      symptomatic management of the condition are discussed. The aim of this critical
      review is to provide a better basis for clinical management of the condition. A
      meta-analysis of data was not done.

PMID- 12190140
TI  - Rapid healing of MRSA infection at the suprafascial radial donor site.
AB  - Methicillin-resistant Staphylococcus aureus (MRSA) infection at the radial
      suprafascial donor site resulted in significant loss of the skin graft, but no
      tendon exposure, in two patients. The complication was successfully managed with
      wound debridement, appropriate antibiotics, a negative-pressure wound dressing
      and early partial-thickness skin grafting. The suprafascial dissection creates a
      donor site that resists both skin graft loss and tendon exposure. It also allows
      early re-grafting with no loss of function in the event of skin graft loss from
      infection. These advantages have not been described previously.

PMID- 12190141
TI  - Preoperative application of limited cone beam computerized tomography as an
      assessment tool before minor oral surgery.
AB  - We describe the preoperative application of limited cone beam computerized
      tomography (CT) using a Dental three-dimensional (3D)-CT as an assessment tool
      before minor oral surgery. The Dental 3D-CT provided 42.7 mm-high and 30 mm-wide
      rectangular solid images. This size covered the height of the mandible with
      standing teeth. Dental 3D-CT clearly demonstrated lesions in the maxillary and
      mandibular bone. Resorption of the bone due to disease expansion was depicted
      more clearly on the Dental 3D-CT than on conventional radiographs. Information
      about lesion location and the relationship between the lesions and their adjacent
      anatomical structures, such as the mandibular canal and maxillary antrum, was
      useful for minor oral surgery. Due to its high resolution and low radiation dose,
      Dental 3D-CT was useful for preoperative examination prior to minor oral surgery.

PMID- 12190142
TI  - Ultrasound-guided surgical drainage of face and neck abscesses.
AB  - An ultrasound-guided surgical drainage technique in which grey-scale and colour
      Doppler ultrasonography were combined is described. The technique was performed
      for eight deep subcutaneous abscesses subsequent to odontogenic infection, and
      provided easy detection and accurate, reliable penetration of abscesses that were
      difficult to locate by physical examination. Colour Doppler ultrasonography is
      particularly useful for differentiating blood vessels from the static space of
      abscesses.

PMID- 12190143
TI  - Intramucosal naevus with pseudoepitheliomatous hyperplasia in the gingiva: a case
      report.
AB  - This article describes the unusual case of an intraoral pigmented naevus with
      pseudoepitheliomatous hyperplasia of the gingiva. A 62-year-old man presented
      with an almost coal-black pigmented and partly white, spotted, dome-shaped
      swelling on the lingual gingiva of the mandible. Histologically, the lesion
      consisted of clusters of round-shaped naevus cells containing melanin granules,
      reactive with both S-100 immunohistochemical stain and Masson-Fontana silver
      stain, and pseudoinvasive squamous nests, reactive with cytokeratin. The
      pathogenesis of the present lesion and problems encountered in its differential
      diagnosis are discussed.

PMID- 12190144
TI  - An unusual bilateral cervical paraganglioma: a case report.
AB  - Paragangliomas are neoplasms originating from paraganglion tissue derived from
      mesoderm, the most common location being adjacent to carotid bifurcation. Rarely
      these tumours can be bilateral. We present here a case of bilateral paraganglioma
      occurring in a young woman. On one side the tumour was arising from the vagus
      nerve and on the other, from the carotid body. Clinical, radiological and
      histopathological features and treatment dilemmas are discussed.

PMID- 12190145
TI  - Crohn's disease, TNF-alpha, and the leaky gut. The chicken or the egg?

PMID- 12190146
TI  - The hepatorenal syndrome: a continuing challenge.

PMID- 12190147
TI  - Autoimmune hepatitis in men: examining the gender gap.

PMID- 12190148
TI  - NASH-related liver failure: one hit too many?

PMID- 12190149
TI  - The "electrical way" to cure gastroparesis.
AB  - The treatment of gastroparesis recently received a heavy blow from the
      restrictions on the use of the prokinetic drug cisapride, but, fortunately, at
      the same time, a nonpharmacological approach, such as gastric electrical
      stimulation, came up again with new techniques. After an ultra-decennial
      experimentation with a large variety of electrical stimuli delivered to the
      gastric wall of animals and patients with gastroparesis, three principal methods
      are available at the moment: gastric electrical pacing, high-frequency gastric
      electrical stimulation, and sequential neural electrical stimulation. The first
      method aims to reset a regular slow-wave rhythm, but is unable to re-establish
      efficient contractions and a normal gastric emptying. High-frequency gastric
      electrical stimulation, although inadequate to restore a normal gastric emptying,
      nevertheless strikingly improves the dyspeptic symptoms, such as nausea and
      vomiting, giving the patients a better quality of life and a more satisfactory
      nutritional status. The last method, neural electrical gastric stimulation,
      consists of a microprocessor-controlled sequential activation of a series of
      annular electrodes which encircle the distal two thirds of the stomach and induce
      propagated contractions causing a forceful emptying of the gastric content. The
      latter method is the most promising, but it has so far only been tested in
      animals and would need to be tested in patients with gastroparesis before it can
      be used as a solution for this disease. All the aforementioned clinical studies,
      however, are not controlled and nearly all were published in abstract form.
      Therefore, further controlled trials are needed to establish which of these
      techniques is more useful for the treatment of gastroparesis.

PMID- 12190150
TI  - Updated guidelines for the diagnosis, surveillance, and therapy of Barrett's
      esophagus.

PMID- 12190151
TI  - Chylous ascites.

PMID- 12190152
TI  - Gastroesophageal reflux disease--should we adopt a new conceptual framework?
AB  - Gastroesophageal reflux disease (GERD) has traditionally been approached as a
      spectrum of diseases. Over the years, this important concept affected our current
      understanding of the pathophysiologic mechanisms resulting in GERD. Additionally,
      it had a profound impact on our therapeutic approach and treatment algorithms.
      However, literature review reveals that there is scant data to support the
      spectrum paradigm. Consequently, we propose categorizing GERD into three unique
      groups of patients: nonerosive reflux disease, erosive esophagitis, and Barrett's
      esophagus. Thus far, studies have demonstrated very little movement between these
      groups. Although the spectrum concept focused our attention on esophageal mucosal
      injury, the new proposed conceptual model shifts our attention to esophageal
      symptoms. Furthermore, dividing GERD into three unique groups of patients will
      allow us to concentrate on the different mechanisms that lead to the development
      of each of these GERD-related disorders and thus help us to focus on the specific
      therapeutic modalities that will benefit each individual group of patients.

PMID- 12190153
TI  - The epidemiology of irritable bowel syndrome in North America: a systematic
      review.
AB  - OBJECTIVE: The aim of this study was to systematically review published
      literature about the prevalence, incidence, and natural history of irritable
      bowel syndrome (IBS) in North America. METHODS: A computer-assisted search of
      MEDLINE, EMBASE, and Current Contents/Science Edition databases was performed
      independently by two investigators. Study selection criteria included: 1) North
      American population-based sample of adults; 2) objective diagnostic criteria for
      IBS (i.e., Rome or Manning criteria); and 3) publication in full manuscript form
      in English. Eligible articles were reviewed in a duplicate and independent
      manner. Data extracted were converted into individual tables and presented in
      descriptive form. RESULTS: The prevalence of IBS in North America ranges from 3%
      to 20%, with most prevalence estimates ranging from 10% to 15%. The prevalences
      of diarrhea-predominant and constipation-predominant IBS are both approximately
      5%. Published prevalence estimates by gender range from 2:1 female predominance
      to a ratio of 1:1. Constipation-predominant IBS is more common in female
      individuals. The prevalence of IBS varies minimally with age. No true population
      based incidence studies or natural history studies were found. In one cohort
      surveyed on two occasions 1 yr apart, 9% of subjects who were free of IBS at
      baseline reported IBS at follow-up producing an onset rate of 67 per 1000 person
      years. In all, 38% of patients meeting criteria for IBS did not meet IBS criteria
      at 1-yr follow-up. CONCLUSION: Approximately 30 million people in North America
      meet the diagnostic criteria for IBS. However, data about the natural history of
      IBS is quite sparse and renewed efforts should be focused at developing
      appropriately designed trials of the epidemiology of IBS.

PMID- 12190154
TI  - Achalasia: a disease of varied and subtle symptoms that do not correlate with
      radiographic findings.
AB  - OBJECTIVE: Dysphagia is the hallmark of achalasia, and when frequent or marked,
      it is believed to be a good predictor of the clinical and radiographic severity
      of disease. We aimed to evaluate the presence and severity of dysphagia and other
      symptoms in achalasia and to correlate these symptoms with findings on barium
      studies. METHODS: The symptoms and radiographs of 38 patients with confirmed
      achalasia were reviewed, 20 prospectively, 18 retrospectively. The number of
      typical and atypical symptoms both initially and at the time of the barium
      esophagogram was tallied. The severity of typical symptoms at the time of the
      barium esophagogram was scored on a point system. A scoring system was also
      devised to rate the severity of the radiographic findings. Symptoms and
      radiographic findings were compared. RESULTS: Dysphagia was the initial symptom
      in only 39% of patients, whereas heartburn, regurgitation, and slow eating
      occurred initially in 24%, 24%, and 16% of patients, respectively. At the time of
      the barium esophagogram, all symptoms were reported by a greater percentage of
      patients than at presentation. The median time period between initial symptoms
      and symptoms reported at the time of the barium esophagogram was 48 months (range
      2-360 months). At the time of the barium esophagogram, the most frequently
      reported symptoms were slow eating and regurgitation (79% each), followed by
      dysphagia (76%), and stereotyped movements (including arching of the neck and
      shoulders, raising of the arms, standing and sitting straight, and walking) with
      meals (60%). The mean number (+/-SD) of initial achalasia-related symptoms per
      patient was 1.34 (+/-0.67) and increased to 5.50 (+/-2.05) at the time of the
      barium esophagogram. The mean typical symptoms score at the time of the barium
      esophagogram was 3.4 (+/-1.5). Most patients (97%) reported a greater number of
      achalasia symptoms at the time of the barium esophagogram than initially, despite
      a mean total radiological score of only 2.58 (out of a maximum of 10 points).
      There was no statistically significant relationship between the total number of
      symptoms at the time of the barium esophagogram and the total radiographic score
      (r = -0.05, and p = 0.77) and between the typical symptom score at the time of
      the barium esophagogram and the total radiographic score (r = -0.11, and p =
      0.51) by Spearman coefficient. CONCLUSIONS: Achalasia is a disease with many
      atypical and subtle symptoms, both initially and over time. Dysphagia is
      initially present in only 39% of patients and is not the most frequently reported
      symptom over time. Neither the severity nor the total number of achalasia-related
      symptoms correlates with the severity of radiographic findings.

PMID- 12190155
TI  - Specialized intestinal metaplasia and carditis at the gastroesophageal junction
      in Chinese patients undergoing endoscopy.
AB  - OBJECTIVE: Specialized intestinal metaplasia (SIM) is often found at a normal
      looking gastroesophageal junction on routine biopsy. The prevalence of SIM in
      Asian populations has not been recorded. Its significance is also unclear. The
      objective of the study was to document the prevalence of SIM at the
      gastroesophageal junction in a Chinese population undergoing endoscopy. METHODS:
      Biopsies were taken at the gastroesophageal junction in 145 patients, both at the
      squamocolumnar junction and immediately below in the gastric cardia. Specimens
      were examined for the type of epithelium (squamous, cardiac, and fundic), the
      presence of SIM, and Helicobacter pylori (H. pylori). RESULTS: Of 145 patients
      who underwent endoscopy, 136 had a normal-looking gastroesophageal junction.
      Cardiac epithelium was found in 100 patients. Of these 100 patients, SIM was
      documented in 34% of patients and carditis in 20%. Patients with SIM were older
      compared with those without SIM (mean age 62 yr and 56 yr, p = 0.035). Carditis
      was more prevalent in patients with SIM. It was present in 11 out of 34 patients
      who had SIM (32.4%) compared with nine in 66 patients (13.6%) without SIM, p =
      0.036. When carditis was found, H. pylori was present at the cardia in 40% of
      patients (eight of 20) compared with only 18% (14 of 80) in those without
      carditis, p = 0.039. CONCLUSIONS: SIM is prevalent at the gastroesophageal
      junction in Chinese patients undergoing endoscopy and is associated with
      carditis. Carditis in turn may be related to H. pylori infection.

PMID- 12190156
TI  - Hiatal hernia size, Barrett's length, and severity of acid reflux are all risk
      factors for esophageal adenocarcinoma.
AB  - OBJECTIVE: The reasons for the development of dysplasia and adenocarcinoma in
      Barrett's mucosa are not well understood. The aims of this study were to
      characterize risk factors for the transition from Barrett's esophagus without
      dysplasia to Barrett's esophagus with high-grade dysplasia or esophageal
      adenocarcinoma. METHODS: A group of 131 patients with high-grade dysplasia or
      esophageal adenocarcinoma were selected as case subjects. A first population of
      2170 patients without gastroesophageal reflux disease (GERD) and a second
      population of 1189 patients with Barrett's esophagus served as two control
      groups. Logistic regression analyses were used to compare the risk factors
      associated with the occurrence of high-grade dysplasia or esophageal
      adenocarcinoma. RESULTS: Patients with high-grade dysplasia or esophageal
      adenocarcinoma shared many characteristics with other forms of severe GERD, such
      as older age, male gender, and white ethnicity. The length of Barrett's esophagus
      and the size of hiatus hernia increased the risk for both conditions. Subjects
      with high-grade dysplasia and adenocarcinoma had more severe acid reflux than
      patients with other forms of GERD. Smoking and alcohol consumption did not affect
      the risk for developing high-grade dysplasia or adenocarcinoma in patients with
      Barrett's esophagus. CONCLUSIONS: High-grade dysplasia and esophageal
      adenocarcinoma seem to stem from an extreme and unfavorable constellation of all
      risk factors that are generally held responsible for the development of GERD and
      Barrett's esophagus.

PMID- 12190157
TI  - Altered hypothalamic cholinergic responses in patients with nonulcer dyspepsia: a
      study of pyridostigmine-stimulated growth hormone release.
AB  - OBJECTIVE: Acetylcholine plays a central and peripheral role in regulating
      gastric motility. In the hypothalamus, it is a key neuroendocrine modulator;
      acting through somatostatin, it brings about the release of growth hormone (GH).
      We measured hypothalamic cholinergic receptor sensitivity in patients with
      nonulcer dyspepsia (NUD) by examining GH release in response to cholinergic
      challenge. METHODS: Forty patients with NUD and 40 healthy comparison subjects
      were administered pyridostigmine (the acetylcholinesterase inhibitor, 120 mg),
      and GH release over a 3-h period was monitored. RESULTS: Calculating response as
      the maximum GH relative to baseline (delta GH), the mean +/- SEM response in the
      patients was 11.9 +/- 1.9 U/L and in the healthy subjects 6.7 +/- 0.7 mU/L (t =
      2.1, df = 78, p = 0.03). Helicobacter pylori status had no appreciable impact on
      GH response with H. pylori-positive patients having a mean response of 10.5 +/-
      2.1 mU/L and negative patients a mean response of 13.2 +/- 3.4 mU/L. Overall,
      patients with NUD release more GH in response to pyridostigmine challenge than
      healthy subjects. CONCLUSIONS: Patients with NUD may have a pathophysiological
      disturbance involving central cholinergic systems.

PMID- 12190158
TI  - The cost-effectiveness of competing strategies for the prevention of recurrent
      peptic ulcer hemorrhage.
AB  - OBJECTIVE: Several strategies exist for the prevention of recurrent ulcer-related
      hemorrhage, yet the cost-effectiveness has not been evaluated and remains
      uncertain. The aim of this study was to compare the cost-effectiveness of
      competing management strategies considering both nonsteroidal anti-inflammatory
      drugs status and the accuracy of Helicobacter pylori (H. pylori) testing.
      METHODS: Decision analysis was used to compare the cost-per-recurrent hemorrhage
      prevented for 11 strategies over 1 yr. Clinical and costs estimates were derived
      from a systematic review of the medical literature and the Medicare Fee Schedule
      and Drug Topics Redbook. Sensitivity analyses were performed for important
      variables. RESULTS: The test/retest eradication strategy with maintenance proton
      pump inhibitor therapy for H. pylori-negative patients was most effective
      (prevention of recurrence in 96.0%). The test/retest eradication strategy with
      maintenance histamine-2 receptor antagonist therapy for H. pylori-negative
      patients was least costly ($1070). The test/retest strategies were dominant with
      average cost-effectiveness ratios of $1118-1310/recurrent hemorrhage prevented
      with maintenance antisecretory therapy. The average cost-effectiveness ratios for
      "selective" H. pylori eradication strategies with maintenance antisecretory
      therapy were $1263-1673. The model was robust to varying estimates over
      prespecified ranges. CONCLUSIONS: Test/retest strategies for H. pylori are cost
      effective for the prevention of recurrent ulcer-related hemorrhage because they
      maximize H. pylori detection and eradication, resulting in fewer recurrent
      hemorrhages and fewer patients requiring antisecretory therapy.

PMID- 12190159
TI  - Do NSAIDs cause dyspepsia? A meta-analysis evaluating alternative dyspepsia
      definitions.
AB  - OBJECTIVE: Nonsteroidal anti-inflammatory drugs (NSAIDs) may be associated with
      dyspepsia, but the relationship is obscured by variations in the terminology used
      to report GI symptoms. Using alternative definitions, we assessed the
      relationship between NSAID use and dyspepsia. METHODS: We searched MEDLINE,
      EMBASE, HEALTHSTAR, and BIOSIS databases (1966-1997) and New Drug Application
      reviews, identifying randomized, placebo-controlled trials (5 days or more
      duration) of any NSAID, reporting original data on GI complications. Based upon
      reported terms describing upper GI symptoms, we derived three definitions:
      strict, using terms synonymous with epigastric pain/discomfort; loose,
      (containing the strict definition plus terms for heartburn, nausea, bloating,
      anorexia, and vomiting); and a loose definition without heartburn terms (the
      loose-less-heartburn definition). Using each definition, we performed a random
      effects model meta-analysis of the relationship between NSAID exposure and
      dyspepsia. RESULTS: Fifty-five published and 37 unpublished controlled NSAID
      trials met our inclusion criteria. The mean duration of the trials was 33.2 days
      (SD 40 days). Application of the strict definition resulted in a pooled risk
      ratio of dyspepsia for NSAIDs compared with placebo of 1.36 (95% CI = 1.11-1.67).
      For the loose definition, the pooled risk ratio was 1.13 (95% CI = 0.98-1.32).
      The loose-less-heartburn definition yielded a pooled risk ratio of 1.19 (95% CI =
      1.03-1.39). In the placebo-treated control groups, the percent of patients
      reporting dyspepsia ranged from 2.3% (strict definition) to 4.2% (loose and loose
      less-heartburn definitions). CONCLUSIONS: Using the strict definition, based
      solely on epigastric pain-related symptoms, NSAIDs increased the risk of
      dyspepsia by 36% (p < 0.05). These findings may be useful in creating a
      standardized definition of NSAID-related dyspepsia.

PMID- 12190160
TI  - An update on recurrent acute pancreatitis: data from five European countries.
AB  - OBJECTIVE: A great number of studies have been published on acute pancreatitis,
      but few have focused on the recurrent form. In this study, we have sought to
      determine the relative frequency and mortality of recurrent acute pancreatitis,
      and also to update our knowledge of its etiological factors. METHODS: Patients
      were selected from a total of 1068 persons included in a previous European study
      of acute pancreatitis. All were admitted to a hospital with an attack of acute
      pancreatitis between January, 1990 and December, 1994. Data for each patient was
      recorded on a standardized form. RESULTS: Of the 1068 with acute pancreatitis,
      288 (27%) had recurrent pancreatitis; the majority (78.8%) were men, with a mean
      age of 43 yr (range 16-95 yr). Regarding etiology, alcohol was the most frequent
      factor (57%), followed by gallstones (25%), other factors (7.6%), and no
      identified factor (10.4%). Of the 288 patients, 17 (5.9%) died, all of whom had
      necrotizing pancreatitis; among all of the patients with necrotizing pancreatitis
      (141 of 288), the mortality was 12.1%. These percentages are lower than those for
      patients who had a single attack (8.5% and 18.6%, respectively), but not to a
      statistically significant degree. Mortality was significantly lower among
      patients with alcoholic pancreatitis (6.9%) than among those with biliary (30%)
      (p < 0.002) or idiopathic pancreatitis (25%) (p < 0.04). Most of the deaths
      (82.4%) occurred at the second attack of pancreatitis. CONCLUSION: Acute
      recurrent pancreatitis remains a frequent disease, with alcohol being the most
      frequent etiological factor. Mortality is similar to that of a single episode of
      acute pancreatitis, and it is significantly lower among patients with alcohol as
      the etiology.

PMID- 12190161
TI  - Synergistic sedation with midazolam and propofol versus midazolam and pethidine
      in colonoscopies: a prospective, randomized study.
AB  - OBJECTIVE: The aim of our study was to compare the safety and efficacy of the
      synergistic sedation with a low dose of midazolam combined with propofol versus
      the standard regimen of midazolam and pethidine for conscious sedation in
      colonoscopy in a group of patients that included a sufficient number of elderly
      patients with several comorbidities. METHODS: A total of 120 consecutive patients
      undergoing colonoscopy in a prospective study were randomly assigned to one of
      two medication regimens (55 patients were over 65 yr). Patients in group A (n =
      64) received i.v. 2 mg (<70 kg b.w.) or 3 mg (>70 kg b.w.) of midazolam and a
      median dose of 80 mg of propofol (range 40-150). Patients in group B (n = 56)
      received i.v. a median dose of 5 mg of midazolam (range 3-7) and 75 mg of
      pethidine (range 50-125). The patient's comfort level was assessed by a 4-point
      scale 24 h after the procedure. The time to recover from sedation was assessed at
      5, 10, and 30 min after the procedure by using the Aldrete score. RESULTS:
      Multivariate stepwise logistic regression analysis revealed that among sex, age,
      duration of the test, American Society of Anesthesiologists' Physical Status
      Classification grade, and the sort of sedation, the synergistic sedation with
      midazolam and propofol was the only factor associated with a higher level of
      patient comfort (chi2 = 5.5, p < 0.05). Additional multivariate stepwise logistic
      regression analysis revealed that among sex, age, duration of the test, American
      Society of Anesthesiologists' Physical Status Classification grade, and the sort
      of sedation, the synergistic sedation with midazolam and propofol was the only
      factor associated with a quicker patient recovery time (chi2 = 24.5, p < 0.01;
      chi2 = 51.7, p < 0.01; chi2 = 148.4, p < 0.01 for Aldrete in 10 min, 20 min, and
      30 min, respectively). The endoscopist's evaluation of patient sedation and
      cardiorespiratory parameters were similar in both groups and in all age groups.
      CONCLUSIONS: Our data suggest that the synergistic sedation with a low dose of
      midazolam combined with propofol was superior to a standard combination of
      midazolam and the opioid pethidine for colonoscopies as far as the patient
      comfort and recovery times are concerned.

PMID- 12190162
TI  - An initial investigation of efficiency in endoscopy delivery.
AB  - OBJECTIVE: The demand for endoscopic services is increasing rapidly. Of the
      several potential mechanisms to improve the supply of endoscopic procedures,
      improved efficiency in the endoscopy unit has received little attention. METHODS:
      We invited 20 experienced endoscopists to participate in an initial evaluation of
      endoscopy efficiency, in which they were observed performing procedures in their
      own unit. Procedure volume per unit time was used as the measure of efficiency.
      Medical directors and head nurses at each endoscopy unit were interviewed
      regarding factors they perceived as most important in limiting procedure volume.
      RESULTS: There was a greater than 3-fold variation in procedure volume score
      between the least efficient and most efficient endoscopists. The clearest trend
      predicting procedure volume score was short room turnover time (p = 0.0004).
      There was a trend toward improved procedure volume among endoscopists using
      another professional to sedate their patients and using two procedure rooms. The
      surveys of medical directors and head nurses suggested that multiple factors
      contribute to limiting procedure volume, but on average each perceived number of
      available doctors is the least important factor in limiting volume. CONCLUSIONS:
      Improving the efficiency of some endoscopists appears to be an important
      potential mechanism to meet the rising demand for endoscopic services. Increasing
      the resources that provide the opportunity for efficiency may be an important
      mechanism for increasing the availability of endoscopic services. Specific
      measures associated with improved efficiency include reduced room turnover times,
      and possibly use of two rooms per endoscopist and sedation by persons other than
      the endoscopist.

PMID- 12190163
TI  - Urinary trypsinogen activation peptide is more accurate than hematocrit in
      determining severity in patients with acute pancreatitis: a prospective study.
AB  - OBJECTIVE: The management of patients with acute pancreatitis is complicated by
      the inability to distinguish mild from severe disease during the early stages. It
      has been previously shown that urinary trypsinogen activation peptide (TAP) and
      hematocrit (Hct) may serve as early predictors of severity in patients with acute
      pancreatitis. To establish which marker is more accurate in the determination of
      severity in patients with acute pancreatitis, a prospective study was performed.
      METHODS: A consecutive series of patients admitted with pain consistent with
      acute pancreatitis and an amylase of three times the upper limit of normal were
      included. The admission and 24-h Hct was obtained. A urine sample was obtained
      within 12 h of admission. Urinary TAP was determined using a modified solid phase
      ELISA. Severity was defined by the Atlanta Symposium, as the presence of organ
      failure and/or pancreatic necrosis. RESULTS: Fifty-eight consecutive patients
      with acute pancreatitis participated. There were 33 men and 25 women with a mean
      age of 60 +/- 19. Thirty-nine patients had mild disease; 19 had severe disease.
      Urinary TAP was elevated in 26 patients. All patients with severe pancreatitis
      were correctly identified as having severe disease by an elevated urinary TAP
      (sensitivity 100%, specificity 77%). The admission Hct was higher than 47 in only
      three patients, all with mild disease. Of the patients with a rise in Hct, eight
      had mild disease, and only one had severe disease. Using a Hct of 44 as a cutoff
      did not affect the accuracy. There was no association between a rise in Hct and
      failure of Hct to decrease in the determination of severity. CONCLUSIONS: In
      comparison to admission Hct, urinary TAP was more accurate in determining
      severity in patients with acute pancreatitis by Atlanta, APACHE II, and Ranson
      criteria. We conclude that urinary TAP is a more accurate predictor of severity
      in patients with acute pancreatitis compared with Hct. Urinary TAP should be used
      to determine severity in patients early in the course of acute pancreatitis.

PMID- 12190164
TI  - Noninvasive assessment of Crohn's disease activity: a comparison of 18F
      fluorodeoxyglucose positron emission tomography, hydromagnetic resonance imaging,
      and granulocyte scintigraphy with labeled antibodies.
AB  - OBJECTIVES: Detection of disease activity in Crohn's disease (CD) is of crucial
      importance for diagnosis and management of the disease. Noninvasive methods for
      monitoring are desirable and comprise hydromagnetic resonance imaging (hydro-MRI)
      and leukocyte scintigraphy. In addition, a recent case report indicated the
      potential of 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) to
      assess CD activity. However, comparative prospective studies are lacking.
      METHODS: Between February, 1999 and August, 2000, 59 patients with CD were
      enrolled in a prospective study to assess disease activity by FDG-PET, hydro-MRI,
      and immunoscintigraphy with anti-nonspecific cross-reacting antigen 95
      antigranulocyte antibodies. In 28 of these patients, colonoscopy could be
      performed. Twelve patients with irritable bowel syndrome and 20 tumor patients
      without gut inflammation served as controls. Results were compared by statistical
      analysis. RESULTS: FDG-PET detected 127 pathological findings (average maximum
      standardized uptake value = 4.4 +/- 1.1) in the terminal/neoterminal ileum (37),
      small bowel (24), and colon (66) of 54 patients with CD, whereas no pathological
      findings were seen in five patients with CD, the control patients with irritable
      bowel syndrome, and the tumor patients without gut inflammation. In contrast,
      examination with hydro-MRI or granulocyte antibodies detected less pathological
      findings in CD patients. Forty-five of the detected foci were accessible to
      endoscopic verification. The correlation of the foci with endoscopic findings
      showed a high specificity (>89%) of all three methods to detect inflamed areas in
      the terminal ileum and colon of patients with CD, although analyses by hydro-MRI
      and granulocyte antibody scan had strikingly lower sensitivities (40.9% and
      66.7%) than FDG-PET analysis (85.4%). CONCLUSIONS: FDG-PET appears to be a
      reliable noninvasive tool for simultaneous detection of inflamed areas in the
      small and large bowel of patients with CD. FDG-PET can be used to detect disease
      activity in the terminal ileum and colon of CD patients with high sensitivity and
      specificity.

PMID- 12190165
TI  - Health-related quality of life in functional GI disorders: focus on constipation
      and resource utilization.
AB  - OBJECTIVE: Functional GI disorders are common in the general population. However,
      their impact on health status and health resource use in Canada has not been well
      examined. We describe 1) health-related quality of life in Canadians with
      functional constipation or other functional GI disorders versus Canadian
      normative data or those without a functional GI disorder and 2) health resource
      utilization in subject's self-reporting of constipation. METHODS: An independent
      research firm was employed to conduct a randomly selected national survey
      examining GI symptoms and personal health. Household members 18 yr or older were
      recruited by a random-digit dial technique. Participants were then mailed a
      questionnaire and data were retrieved by a follow-up phone call. All functional
      GI disorders were defined using Rome II criteria, and constipation was further
      defined using self-report. Health-related quality of life was assessed using the
      Short Form 36. RESULTS: One thousand one hundred forty-nine subjects (49.3% male)
      with a mean age of 42.2 yr completed the survey. The prevalence of any Rome II
      functional GI disorder was 61.7%. The rate of functional constipation was 14.9%,
      whereas that of self-reported constipation was 27.2%. The mean physical and
      mental component summary and eight subscores of the Short Form 36 were
      significantly lower (p < 0.05) than Canadian norms for both self-reported
      constipation and Rome II functional constipation. Subjects with no GI disorder
      had significantly better Short Form 36 scores than the Canadian norms. The rate
      of physician visits for constipation was strongly predicted by the physical
      component of the Short Form 36. Most subjects (66.2%) were satisfied with their
      current constipation treatment. CONCLUSIONS: Constipation is common in the
      Canadian population and significantly impairs health-related quality of life.
      Poor quality of life is an important predictor of health care utilization in
      these subjects.

PMID- 12190166
TI  - Psychological disorder and severity of inflammatory bowel disease predict health
      related quality of life in ulcerative colitis and Crohn's disease.
AB  - OBJECTIVE: The determinants of health-related quality of life in inflammatory
      bowel disease are not completely understood. The present study aimed to assess
      two factors in patients with inflammatory bowel disease: a) whether health
      related quality of life is independently associated with both bowel disease
      severity and psychological disorder, and b) whether Crohn's disease is associated
      with more marked psychological disorder than ulcerative colitis. METHODS: 116/170
      (68%) consecutive patients with inflammatory bowel disease attending a GI clinic
      (37 patients with ulcerative colitis, 75 patients with Crohn's disease, and four
      unspecified) completed the following self-report questionnaires: demographic
      details, a modified disease activity index, a total severity measure, the
      Hospital Anxiety and Depression Scale, and the Short Form-36. RESULTS: Thirty
      patients (25.9%) scored 11 or more on either the depression or anxiety subscales
      of the Hospital Anxiety and Depression Scale indicating probable psychological
      disorder; 55% (47.4%) scored over 8 indicating possible psychological disorder.
      Stepwise multiple regression analyses showed that both psychological symptoms and
      disease severity or activity contributed independently to impaired health-related
      quality of life. After severity of disease was taken into account, there were no
      significant differences between Crohn's disease and ulcerative colitis in terms
      of depression scores and health-related quality of life. CONCLUSIONS: The
      presence of psychological disorder in inflammatory bowel disease contributes to
      poor health-related quality of life, regardless of the severity of the condition.
      Detection and treatment of psychological disorder in inflammatory bowel disease
      carries the potential to improve health-related quality of life for these
      patients.

PMID- 12190168
TI  - Inflammatory bowel disease in children 5 years of age and younger.
AB  - OBJECTIVES: Clinicians are becoming increasingly aware that inflammatory bowel
      disease (IBD) can affect all age groups, although it has not been well described
      in infants and young children. Our aim was to evaluate early onset IBD in
      patients 5 yr of age and younger. METHODS: Medical records of patients diagnosed
      with early onset IBD at The Children's Hospital of Philadelphia between 1977 and
      2000 were reviewed. Patients were divided into three categories: those with
      Crohn's disease (CD), those with ulcerative colitis (UC), and those with
      indeterminant colitis (IC). RESULTS: A total of 82 patients fulfilled the
      criteria. In 12 patients (15%), the IBD diagnosis was changed during the course
      of illness. At the end of the follow-up period, linear growth failure was present
      in 10 of 35 (29%) children with CD, one of 30 (3%) with UC, and three of 17 (18%)
      with IC. Failure to thrive was a frequent presenting symptom in children with CD
      (44%) and IC (39%), whereas in all four patients with UC and failure to thrive
      the diagnosis was subsequently changed to CD or IC. A high proportion of patients
      with CD had large bowel (89%), and perianal (34%) disease. None of the tested
      patients were positive for anti-Saccharomyces cerevisiae antibody (ASCA), and 10
      tested positive for perinuclear antineutrophil cytoplasmic antibody (three of
      five patients with CD, five of seven with UC, and two of three with IC).
      CONCLUSIONS: Failure to thrive, at the time of presentation, is indicative of a
      final diagnosis of CD or IC, not UC. Linear growth failure is a common finding in
      patients with early onset CD. A high proportion of patients with CD have failure
      to thrive, colonic, and perianal disease. The IBD serology panel is of limited
      clinical relevance in providing definitive diagnostic information in this
      pediatric population.

PMID- 12190167
TI  - Anti-tumor necrosis factor treatment restores the gut barrier in Crohn's disease.
AB  - OBJECTIVES: A primary defect of the tight junctions and, hence, increased
      intestinal epithelial permeability has been proposed as a basic pathogenic event
      in Crohn's disease. Challenge of the mucosal immune system by the commensal gut
      flora would then result in chronic inflammation. Alternatively, increased
      permeability could be the result of inflammation. Our aim was to study intestinal
      permeability in refractory Crohn's disease before and after treatment with
      monoclonal chimeric antibodies directed against tumor necrosis factor (TNF) to
      investigate whether the abnormal permeability persists after control of
      inflammation. METHODS: Twenty-three patients with active Crohn's disease were
      evaluated before and 4 wk after a single infusion of 5 mg/kg infliximab.
      Intestinal permeability was studied by measurement of urinary excretion of 51Cr
      EDTA after oral intake. RESULTS: The increased permeation of 51Cr-EDTA through
      the small intestine (1.63% interquartile range [IQR] 1.06-2.07) and the overall
      permeation (3.27% IQR 2.40-4.38) before therapy decreased significantly after
      infliximab infusion to values (1.04% IQR 0.74-1.54 and 2.42% IQR 2.03-2.80,
      respectively) in the range of those found in normal volunteers (1.12% IQR 0.85
      1.58 and 2.28% IQR 1.88-2.86, respectively). CONCLUSION: Inhibiting the
      proinflammatory cytokine tumor necrosis factor dramatically reduces gut
      inflammation and largely restores the gut barrier in Crohn's disease. Our data
      confirm the central role of TNF in gut barrier modulation in inflammatory
      conditions in vivo.

PMID- 12190169
TI  - Corticosteroid-induced osteoporosis: does it occur in patients with Crohn's
      disease?
AB  - OBJECTIVE: In Crohn's disease, osteoporosis is frequently found. However, the
      etiology of osteoporosis remains unclear. The aim of this study was to determine
      disease-related variables predictive for impaired bone mineral density (BMD).
      METHODS: A total of 91 patients with Crohn's disease who were admitted for BMD
      assessment were enrolled in the study. BMD was measured at the femoral neck and
      lumbar spine by dual energy x-ray absorptiometry (DXA). Results were expressed as
      T-score and as age- and sex-matched Z-score. Data were obtained by a
      questionnaire and from patients' medical records. Stepwise linear regression
      analysis was used to determine independent variables predictive for BMD. RESULTS:
      Mean age at BMD assessment was 41 +/- 12 yr, duration of disease 11.6 +/- 8.5 yr,
      and body mass index (BMI) 23.0 +/- 4.1 kg/m2. The cumulative dose of steroids
      used was 18.7 +/- 19.2 g. Mean Z-scores were less than zero (spine, -1.1 +/- 1.3
      SD; femur, -1.1 +/- 1.2 SD; p < 0.0001). A total of 27 patients (30%) fulfilled
      the World Health Organization criteria for osteoporosis and 46 patients (50%) for
      osteopenia. Osteoporotic patients used more corticosteroids and had longer
      duration of disease, lower BMI, and more bowel resections than patients with
      normal BMD. However, in the linear regression analysis, the only significant
      independent predictors for BMD of the lumbar spine and femoral neck were BMI and
      history of bowel resections. BMI and history of resections together accounted for
      28% of BMD Z-scores. CONCLUSIONS: BMI and a history of bowel resections were
      significant predictive variables for BMD. Despite the high dose of steroids used
      in this study, no detrimental effect could be demonstrated as independent
      predictor for osteoporosis.

PMID- 12190170
TI  - Etiology of nonresponsive celiac disease: results of a systematic approach.
AB  - OBJECTIVES: Nonresponse or relapse of symptoms is common in patients with celiac
      disease treated with gluten free diet. Refractory sprue (RS) is defined as
      initial or subsequent failure of a strict gluten-free diet to restore normal
      intestinal architecture and function in patients who have celiac-like
      enteropathy. The aims of this study were: 1) to identify causes of persistent
      symptoms in patients referred with presumed diagnosis of nonresponsive celiac
      disease (NCD); and 2) to characterize patients with true RS. METHODS: Patients
      were identified who had been systematically evaluated for NCD between January
      1997, and May 2001. Patient records and small bowel biopsy results were reviewed.
      RESULTS: A total of 55 patients were referred with a presumed diagnosis of NCD.
      Six did not have celiac disease and had other diseases responsible for their
      symptoms. Diarrhea, abdominal pain, and weight loss were the most common reasons
      for evaluation in cases of NCD, whereas weight loss, steatorrhea, and diarrhea
      were the most common presenting features of RS (nine patients). Of the 49
      patients with celiac disease, 25 were identified as having gluten contamination.
      Additional diagnoses accounting for persistent symptoms included: pancreatic
      insufficiency, irritable bowel syndrome, bacterial overgrowth, lymphocytic
      colitis, collagenous colitis, ulcerative jejunitis, T-cell lymphoma, pancreatic
      cancer, fructose intolerance, protein losing enteropathy, cavitating
      lymphadenopathy syndrome, and tropical sprue. CONCLUSIONS: Based on this study,
      we conclude the following: 1) gluten contamination is the leading reason for NCD;
      2) of NCD cases, 18% are due to RS; and 3) alternative diseases or those
      coexistent with celiac disease and gluten contamination should be ruled out
      before a diagnosis of RS is made.

PMID- 12190171
TI  - Combining infliximab with 6-mercaptopurine/azathioprine for fistula therapy in
      Crohn's disease.
AB  - OBJECTIVES: Fistulas occur in about one third of patients with Crohn's disease
      and rarely heal spontaneously. Conventional medical and surgical therapy often
      fails. The anti-TNF-alpha antibody infliximab offers a novel therapeutic option.
      By this approach, closure of fistulas was reported in 45% of cases. However,
      after discontinuation of therapy, most fistulas recurred. Azathioprine and 6
      mercaptopurine (6-MP) are effective drugs in Crohn's disease and lead to closure
      of fistulas in 30-40% of cases. Thus, the aim of this study was to evaluate the
      combination of infliximab with 6-mercaptopurine/azathioprine as therapy for
      fistulas in patients with Crohn's disease. METHODS: A total of 16 patients (mean
      age 37 yr) with Crohn's fistulas resistant to conventional measures were treated
      with a combination of three or four infusions of infliximab and long term 6
      MP/azathioprine. In all, 13 patients had perianal fistulas, two had abdominal
      fistulas, and one patient had both perianal and recto-vaginal fistulas. Therapy
      success was defined as complete closure of fistulas for a minimum observation
      period of 6 months after fistula closure. RESULTS: In 12 (75%) of the 16
      patients, we observed complete closure of the fistulas that persisted for >6
      months (median follow-up 10 months, range 6-11 months). The median time to
      complete closure of fistulas was 14 days (range 2-36 days). In four patients,
      therapy success was not achieved. CONCLUSION: Our pilot study reveals that
      concomitant and long term 6-MP/azathioprine therapy could prolong the effect of
      an initial infliximab therapy on fistula closure in patients with Crohn's
      disease. These data prompt larger controlled trials.

PMID- 12190172
TI  - Kallikrein-kinin system activation in Crohn's disease: differences in intestinal
      and systemic markers.
AB  - OBJECTIVES: Observations in experimental models and in human ulcerative colitis
      suggest that activation of the kallikrein-kinin system plays a role in the
      pathogenesis of inflammatory bowel disease. The aim of this study was to assess
      activation of the plasma and tissue kallikrein-kinin system in Crohn's disease.
      METHODS: We studied plasma inflammatory and contact system parameters in 36
      patients with Crohn's disease and in 36 control subjects with noninflammatory GI
      diseases. We also obtained tissue samples from the involved intestine of 12
      patients with Crohn's disease, and from normal peritumoral tissue (12 patients)
      and diverticulitis tissue (seven patients) as controls. Full-thickness sections
      were tested for intestinal tissue kallikrein reactivity with a specific antibody.
      RESULTS: In Crohn's disease patients and controls, plasma levels of
      prekallikrein, factor XI, high molecular weight kininogen and its cleaved form
      were normal. Crohn's disease patients had significantly higher levels of antigen
      and functional Cl-inhibitor (+22%, +12%) than did controls (p = 0.005, p =
      0.004). After surgical resection, antigen and functional Cl-inhibitor
      significantly decreased in Crohn's disease patients (-22%, -15%; p = 0.035, p =
      0.006). Intestinal tissue kallikrein immunoreactivity was absent (75%) or weak
      (25%) in the goblet cells from Crohn's disease tissue sections but was normal in
      controls, with a highly significant difference in the staining score (p =
      0.0001). Intestinal tissue kallikrein immunoreactivity in the interstitium was
      higher in Crohn's disease than in normal and diverticulitis samples (p = 0.0001
      and p = 0.001, respectively). CONCLUSIONS: Our observations suggest that
      intestinal tissue kallikrein is involved in the inflammatory process in Crohn's
      disease. The lack of contact system activation in peripheral blood might be
      related to the high plasma levels of Cl-inhibitor, the most important inhibitor
      of the contact system in the circulation.

PMID- 12190173
TI  - Effect of misoprostol on ibuprofen-induced renal dysfunction in patients with
      decompensated cirrhosis: results of a double-blind placebo-controlled parallel
      group study.
AB  - OBJECTIVES: Patients with cirrhosis are prone to develop renal failure upon
      administration of nonsteroidal anti-inflammatory drugs. The aim of the present
      study was to determine the safety and efficacy of misoprostol (400 microg) in two
      repeated doses for the prevention of ibuprofen-induced decrements in renal
      function in decompensated cirrhotics. METHODS: Patients were given ibuprofen (800
      mg) with either misoprostol (n = 9) or a placebo (n = 10). Sixty minutes later
      another dose of misoprostol or the placebo was administered. Renal function tests
      were assessed by clearance techniques. RESULTS: Administration of ibuprofen with
      a placebo caused significant decreases in urinary output, inulin clearance,
      sodium excretion, osmolar clearance, free water clearance, and urinary
      prostaglandin E2 excretion. Coadministration of ibuprofen and the first
      misoprostol dose maintained urinary output and sodium excretion, and caused an
      increase in free water clearance. These changes were maintained only for 1 h.
      Administration of the second dose of misoprostol temporarily improved inulin and
      creatinine clearances. Half the patients who received misoprostol suffered from
      episodes of chills, fever, and diarrhea. CONCLUSION: Ibuprofen causes renal
      dysfunction in decompensated cirrhotics, whereas misoprostol may have some
      protective renal effects, which are, however, short lived and clinically
      insignificant. Because of side effects, misoprostol should be used with caution
      in these patients.

PMID- 12190174
TI  - Immune thrombocytopenic purpura in patients with chronic hepatitis C virus
      infection.
AB  - OBJECTIVE: Hepatitis C virus (HCV) infection has been associated with the
      production of autoantibodies and the development of several autoimmune disorders.
      Immune thrombocytopenic purpura (ITP) is an immune-mediated syndrome of unknown
      etiology characterized by the presence of autoantibodies against platelet
      membrane proteins. METHODS: Retrospective chart review. RESULTS: Seven patients
      with chronic HCV infection (five with cirrhosis and two with chronic active
      hepatitis) developed thrombocytopenia, out of proportion to their liver disease,
      and were diagnosed with ITP based on the presence of anti-platelet antibodies and
      their response to treatment. The number of patients with ITP which occurred in a
      population of 3440 HCV patients seen over this time interval is much greater than
      would be expected by chance (p < 0.00001). Six patients required treatment and
      four required hospitalization. Four of the six responded to corticosteroids
      alone. Both of the patients who failed to respond to corticosteroids responded to
      cyclophosphamide. No mortality occurred from complications of thrombocytopenia.
      CONCLUSIONS: ITP occurs more commonly in patients with chronic HCV infection than
      would be expected by chance. This should be considered in patients with liver
      disease and unexplained thrombocytopenia, as well as in patients with newly
      diagnosed ITP. Evaluation of antiplatelet antibodies, using an antigen-specific
      assay, was useful in supporting this diagnosis. Therapy with either
      corticosteroids or cyclophosphamide was successful in the six patients who
      required treatment.

PMID- 12190175
TI  - Hepatorenal syndrome: diagnostic accuracy, clinical features, and outcome in a
      tertiary care center.
AB  - OBJECTIVES: Hepatorenal syndrome (HRS) is a common and life-threatening entity
      that is associated with advanced liver disease. There are limited data on
      predisposing or precipitating factors related to the development of this
      syndrome. The aims of this study were: 1) to determine the accuracy of the
      diagnosis of HRS in an urban tertiary care center; 2) to compare features of HRS
      with those of non-HRS renal failure; and 3) to document the precipitating factors
      for HRS in this setting. METHODS: We conducted a retrospective chart review of 46
      patients at the Health Sciences Center in Winnipeg, Manitoba, who were diagnosed
      with HRS within the last 10 yr. In addition to assessing the accuracy of the
      diagnosis of HRS (as defined by the International Ascites Club), we also
      developed a database that included clinical and biochemical features of these
      patients' liver disease, possible predisposing factors, precipitating events,
      etiology of cirrhosis, and mortality rates. A cohort of 19 patients with advanced
      liver disease and renal failure not ascribed to HRS (non-HRS) served as controls.
      RESULTS: A total of 46 patients were labeled as having HRS during their hospital
      stay, of whom 27 (59%) fulfilled International Ascites Club criteria. Their mean
      age was 51.8 +/- 12.1 yr, and 67% were male. Demographic and biochemical findings
      in the HRS patients were similar to those of the non-HRS patients. Hepatic
      encephalopathy (p < 0.03) and jaundice (p < 0.01) more commonly preceeded renal
      failure in the HRS group than in the controls. The most common predisposing
      factor for HRS was alcohol abuse. Precipitating factors for HRS included
      infection in 48% patients, GI bleeding in 33%, and over paracentesis in 27%. Drug
      induced renal disease was significantly more common in patients with non-HRS
      renal failure. Contrary to previous reports, nonsteroidal anti-inflammatory drugs
      were not common precipitating factors of HRS. Alcohol-related liver disease was
      the most common underlying etiology of liver disease in all patients who
      developed renal failure but was proportionally higher in the HRS group. Mortality
      was almost universal in both groups, regardless of the cause of renal failure.
      CONCLUSIONS: The diagnostic accuracy (or lack thereof) of HRS highlights the
      importance of ensuring that diagnostic criteria are met in studies describing the
      natural history and/or the results of therapeutic intervention in HRS. Alcohol
      abuse is a common predisposing factor for the development of HRS. Infection, GI
      bleed, and aggressive paracentesis were the most common precipitating factors for
      HRS.

PMID- 12190177
TI  - Subacute liver failure in obese women.
AB  - OBJECTIVES: Steatosis or steatohepatitis, common conditions associated with
      obesity, are usually considered to be stable or only slowly progressive. We have
      encountered a small number of patients with a history of obesity and a subacute
      course of liver failure over a period of 4-16 wk from the onset of symptoms. The
      patients had findings suggestive of an acute exacerbation of previously
      unrecognized nonalcoholic steatohepatitis (NASH). METHODS: The patients were
      ascertained from our liver disease registry, which, at the time of the study,
      contained 2380 patients: 167 had NASH and 215 had cryptogenic cirrhosis. Five of
      these patients were identified with a subacute course of their illness. RESULTS:
      The patients were female, aged 41-65 yr, and obese (BMI >30, mean 41 +/- 9, range
      32-52). One patient had type 2 diabetes treated by diet alone and one had a
      history of glucose intolerance. None had known prior liver disease and two had no
      prior medical problems. All five presented with fatigue and lethargy. Over 4-16
      wk, the patients developed frank encephalopathy, ascites, jaundice, and
      multiorgan failure. An extensive evaluation revealed no clear etiology of their
      disease, although initial imaging studies consistently showed evidence of
      previously unrecognized cirrhosis. Four patients died from complications of liver
      failure and the fifth patient underwent OLT. Histology revealed cirrhosis with
      variable numbers of balloon cells in all five patients, frank steatohepatitis in
      three, necrosis in two, and microvesicular (with macrovesicular) steatosis in
      one. CONCLUSIONS: These patients, all obese and middle-aged women with no history
      of liver disease, had previously unrecognized cirrhosis and sudden deterioration
      of uncertain cause. We speculate, based on the clinical and histological
      findings, that these patients had undiagnosed NASH with silent progression to
      cirrhosis followed by subacute liver failure. We propose that obesity-related
      liver disease may infrequently present as severe, subacute illness.

PMID- 12190176
TI  - Gender effects and synergisms with histocompatibility leukocyte antigens in type
      1 autoimmune hepatitis.
AB  - OBJECTIVES: Our goals were to determine the effect of gender on the clinical
      features and treatment outcome of type 1 autoimmune hepatitis, and to assess
      synergisms with the known genetic risk factors. METHODS: Clinical findings and
      treatment outcomes were compared in 144 women and 41 men who were also assessed
      for HLA DR3, HLA DR4, HLA DR3 and DR4 alleles, and the DRB1*1501-DQA1*102
      haplotype by polymerase chain reaction. A total of 102 healthy men and women were
      similarly typed. RESULTS: Women were distinguished from men by higher frequencies
      of concurrent immune diseases (34% vs 17%, p = 0.05) and HLA DR4 (49% vs 24%, p =
      0.007), as had been previously reported. Women, however, had a higher occurrence
      of non-DRB1*0401 DR4 alleles than men (15% vs 0%, p = 0.02), and men had a lower
      frequency of these alleles than did normal male subjects (0% vs 16%, p = 0.04).
      Men and women responded similarly to therapy. Treatment failure occurred more
      frequently in men only if they had HLA DR3 and women had HLA DR4 (25% vs 4%, p =
      0.01). The DRB1*1501-DQA1*102 haplotype did not affect outcome. CONCLUSIONS:
      Gender influences susceptibility and clinical manifestations, but not outcome.
      Women have HLA DR4 more commonly than men, but this difference relates to their
      higher frequency of non-DRB1*0401 DR4 alleles. Female gender may promote risk
      associated with different HLA DR4 alleles.

PMID- 12190178
TI  - Ursodeoxycholic acid for primary biliary cirrhosis: final results of a 12-year,
      prospective, randomized, controlled trial.
AB  - OBJECTIVES: The aim of this study was to evaluate whether ursodeoxycholic acid
      (UDCA) has any effect on the development of liver decompensation and on survival
      of patients with primary biliary cirrhosis (PBC). METHODS: A total of 86 patients
      with compensated PBC were randomly assigned to receive UDCA (n = 43) or to remain
      untreated (controls, n = 43). There was no significant difference in the baseline
      characteristics between the two groups. Mean follow-up was 7.3 +/- 3.0 yr in the
      UDCA and 8.1 +/- 3.1 yr in the control group. Fourteen control patients were
      crossed-over to UDCA therapy after a median of 3.5 yr (range 2-8 yr), at their
      own request. RESULTS: Liver decompensation developed in 41 patients (22 in the
      UDCA and 19 in the control group) and liver death or transplantation in 33 (19 in
      the UDCA and 14 in the control group) patients. There was no significant
      difference in the probability of development of liver decompensation, liver
      death, or transplantation (by log-rank test) between UDCA-treated and control
      patients, whether by an intention-to-treat or by treatment-as-received analysis.
      CONCLUSIONS: UDCA was not found to have any demonstrable effect on the long-term
      outcome of PBC and did not improve the survival of PBC patients.

PMID- 12190179
TI  - Prevalence of hepatitis C and coinfection with HIV among United States veterans
      in the New York City metropolitan area.
AB  - OBJECTIVES: The aims of this study were to determine the prevalence of hepatitis
      C virus (HCV) infection and its risk factors, as well as the prevalence of
      coinfection with HIV and its risk factors, among patients with confirmed HCV
      infection. METHODS: In a 1-day cross-sectional HCV survey at six Veterans Affairs
      Medical Centers in the New York City metropolitan area, all 1943 patients
      undergoing phlebotomy for any reason were asked to be tested for HCV antibody by
      enzyme immumoassay (EIA). A total of 1098 patients (57%) agreed to HCV testing,
      1016 of whom also completed a questionnaire on demographics and HCV risk factors.
      All HCV EIA(+) samples were confirmed by HCV RNA and HCV recombinant immunoblot
      assay (RIBA) antibody testing and were also tested for HCV viral load, HCV
      genotype, and antibodies to HIV in a blinded fashion. RESULTS: The prevalence of
      confirmed HCV infection was 10.6% (95% CI = 8.7-12.4%), and the prevalence of HCV
      viremia was 8.2% (95% CI = 6.6-9.8%). The rate of HCV viremia among anti-HCV(+)
      patients was 77.6%, and HCV genotype 1 was present in 87.5% of viremic patients.
      Independent risk factors for HCV infection were injection drug use (OR = 35.6,
      95% CI = 16.9-75.2), blood exposure during combat (OR = 2.6, 95% CI = 1.2-5.7),
      alcohol abuse (OR = 2.4; 95% CI = 1.2-4.8), and service in the Vietnam era (OR =
      2.1; 95% CI = 1.0-4.5). Coinfection with HIV was present in 24.8% of anti-HCV(+)
      patients. The only independent risk factor for coinfection was age <50 yr (OR =
      3.7, 95% CI = 1.1-12.1). CONCLUSIONS: U.S. veterans who are receiving medical
      care at VA medical centers in the New York City metropolitan area have a much
      higher rate of chronic hepatitis C than the general population, with a high
      frequency of genotype 1. Coinfection with HIV is very common in patients with
      confirmed HCV infection, and these patients should routinely be offered HIV
      testing.

PMID- 12190180
TI  - Xanthine oxidoreductase activity in human liver disease.
AB  - OBJECTIVES: The aim of this study was to investigate the level and the form of
      xanthine oxidoreductase (XOR) in severely diseased human livers, to ascertain
      whether the modifications of the enzyme activity reported in experimental
      pathology also occur in human liver disease. METHODS: Total, dehydrogenase, and
      oxidase activities of XOR were measured in samples of human liver removed for
      transplantation or partial hepatectomy. Samples included four groups: 1)
      histologically normal liver tissue, adjacent to metastases from extrahepatic
      tumors (controls), 2) liver with virus-related cirrhosis; 3) liver with virus
      negative cirrhosis, and 4) hepatocellular carcinoma tissue (HCC). RESULTS: The
      level of total XOR was significantly higher in liver with virus-related
      cirrhosis, but not in virus-negative cirrhosis, than in controls. In virus
      positive cirrhosis, the total XOR activity correlated positively with the level
      of ALT. The percentage of XOR oxidase activity in cirrhotic liver, regardless of
      virus infection, correlated positively with aspartate amino-transferase,
      bilirubin concentration, and partial thromboplastin time, and negatively with
      prothrombin time. The activity of XOR was significantly lower in HCC than in
      control tissue or in a nonneoplastic area of the same liver. CONCLUSIONS:
      Consistent with previous reports in experimental pathology, the level of XOR was
      increased in cirrhotic liver, in association with viral infection. This increment
      correlated with ALT, suggesting a relationship between XOR activity and the
      extent of liver injury caused by viral replication. The percentage of oxidase
      activity seems to be correlated with tissue damage and consequent liver
      impairment. The low XOR activity observed in HCC is consistent with reported
      experimental pathology.

PMID- 12190182
TI  - Unsaturated iron binding capacity and transferrin saturation are equally reliable
      in detection of HFE hemochromatosis.
AB  - OBJECTIVE: Unsaturated iron binding capacity (UIBC) has been proposed as an
      inexpensive alternative to transferrin saturation for detection of hereditary
      hemochromatosis. The aim of this study was to compare, in a hospital referral
      clinic, the reliability of transferrin saturation and UIBC for detection of
      subjects who have inherited HFE (HLA-asociated iron overload) genotypes
      predisposing to iron overload. METHODS: Serum transferrin saturation, UIBC, and
      ferritin were tested in 110 consecutive subjects. Optimum thresholds were
      determined from receiver operating characteristic curves. RESULTS: Of 110
      subjects, 44 carried significant HFE mutations (C282Y/C282Y or C282Y/H63D). In
      genetically predisposed subjects with biochemical expression, the optimum
      threshold for transferrin saturation was 43%, giving a sensitivity of 0.88 and
      specificity 0.95. For UIBC, the optimum threshold was 143 microg/dL (25.6
      micromol/L), giving a sensitivity of 0.91 and specificity of 0.95. In patients
      referred with a family history or clinical suspicion of hemochromatosis,
      transferrin saturation and UIBC were highly reliable predictors of genotype. In
      patients referred for investigation of abnormal liver enzymes without a known
      family history of hemochromatosis, a normal transferrin saturation or normal UIBC
      was highly reliable in excluding hemochromatosis. CONCLUSIONS: Transferrin
      saturation and UIBC have equal reliability in ability to predict hemochromatosis.
      UIBC should be considered as an alternative to transferrin saturation in
      detection of hemochromatosis.

PMID- 12190183
TI  - The site distribution and characteristics of colorectal adenomas in Hispanics: a
      comparative study.
AB  - OBJECTIVES: No data are available about the site distribution and characteristics
      of colorectal adenomas in Hispanics. The purpose of this study is to study the
      site distribution and characteristics of adenomas in Hispanics as compared to
      whites. METHODS: We retrospectively reviewed the records of all patients who had
      colonoscopies with resection of adenomatous polyps. Patients were classified by
      age, sex, and race. Polyps were classified by site and histology. RESULTS: Nine
      hundred ninety-four patients were included in the final analysis. These included
      541 whites and 453 Hispanics. The mean age was 60 yr. The site distributions of
      adenomas were similar (p = 0.32), and adenoma histologies were similar (p =
      0.16). Thirty percent of patients had no polyps in the descending colon (27%,
      Hispanics; 31%, whites). CONCLUSION: Hispanics and whites have similar site
      distributions of colorectal adenomas and similar adenoma histologies. Screening
      modalities excluding the area proximal to the splenic flexure would miss about
      30% of the polyps in both populations.

PMID- 12190181
TI  - Influence of interleukin-10 gene promoter polymorphisms on disease progression in
      patients chronically infected with hepatitis B virus.
AB  - OBJECTIVES: The role of host genetic factors in chronic hepatitis B virus (HBV)
      infection is not fully understood. We studied the influence of tumor necrosis
      factor-alpha (TNF-alpha) and interleukin-10 (IL-10) gene promoter polymorphisms
      on disease progression in HBV carriers. METHODS: The sample population included
      213 Japanese HBV carriers and 52 healthy volunteers. Of 213 HBV carriers, 66 were
      considered to be asymptomatic carriers based on the sustained normalization of
      serum ALT together with seropositivity for the antibody to hepatitis B e antigen
      (anti-HBe), and 147 were found to have chronic progressive liver disease
      including cirrhosis. Five biallelic polymorphisms in the TNF-alpha gene promoter
      and three biallelic polymorphisms in the IL-10 gene promoter were analyzed by
      polymerase chain reaction in combination with direct sequencing or restriction
      fragment length polymorphism assay. RESULTS: Allelic distributions of both gene
      promoters were not significantly different between HBV carriers and healthy
      volunteers. In HBV carriers, the TNF-alpha gene promoter polymorphisms were not
      linked to disease progression. In contrast, allelic frequencies of T and A at
      positions -819 and -592, respectively, in the IL-10 gene promoter, as well as the
      frequencies of ATA haplotype at positions -1082/-819/-592 (which is characterized
      with low capacity for IL-10 production), were significantly higher in
      asymptomatic carriers than in patients with chronic progressive liver disease.
      Even after adjusting for individuals positive for anti-HBe, such a relationship
      could be found between the two groups. CONCLUSION: In chronic HBV infection,
      inheritance of the IL-10 gene promoter polymorphisms is involved in a host
      genetic factor that is relevant to disease progression.

PMID- 12190184
TI  - Serum selenium and risk of large size colorectal adenomas in a geographical area
      with a low selenium status.
AB  - OBJECTIVE: Selenium is a fundamental nutrient to human health that might have
      anticarcinogenic effects. Previous studies have assessed the possible
      relationship of selenium status to colorectal adenomas with controversial
      results. We primarily aimed to assess the relationship of serum selenium status
      with the presence of large size colorectal adenomas in subjects living in a poor
      selenium region. The serum selenium status in colorectal cancer was also
      evaluated. METHODS: Serum selenium levels were measured in 28 patients with large
      size sporadic adenomatous polyps, 24 patients with colorectal adenocarcinomas,
      and 35 age-matched healthy individuals. A logistic regression analysis was
      performed to assess the relationship of serum selenium to colorectal adenomatous
      polyps after adjusting for confounding variables (age, sex, smoking habit, and
      alcohol drinking). RESULTS: Among subjects aged < or = 60 yr, mean serum selenium
      levels were significantly lower in both patient groups (adenoma, 57.9 +/- 4.3
      microg/L; cancer, 43.7 +/- 6.6 microg/L) than in healthy controls (88.9 +/- 8
      microg/L) (p = 0.0001). There were no difference among subjects > 60 yr old. A
      significant inverse association between selenium status and the diagnosis of
      large size adenomatous polyps after adjusting for confounding variables was found
      (adjusted p = 0.029). Subjects with higher selenium status (> or = 75th
      percentile value of 82.11 microg/L) had a lower probability (OR = 0.17, 95% CI =
      0.03-0.84) to be in the adenoma group than subjects with lower selenium status (<
      82.11 microg/L). This association was more marked in subjects aged < or = 60 yr
      (adjusted p value = 0.04, OR = 0.08, 95% CI = 0.007-0.91), and was not
      significant in older subjects. CONCLUSIONS: Results suggest that high selenium
      status may decrease the risk of large size adenomas in a low selenium region, and
      that this preventive effect seems to be exclusive to subjects < or = 60 yr. These
      results will need to be confirmed in additional epidemiological studies before
      recommending selenium supplementation in patients with colon adenomas.

PMID- 12190186
TI  - Urethral dilators.

PMID- 12190185
TI  - Natural history of colorectal nonpolypoid adenomas: a prospective colonoscopic
      study and relation with cell kinetics and K-ras mutations.
AB  - OBJECTIVE: Serial colonoscopic observations were prospectively conducted to
      elucidate the natural history of nonpolypoid tumors. Furthermore, to clarify
      whether cell kinetic status affects the tumor development, proliferative indices,
      apoptotic indices, and K-ras codon 12 point mutations on biopsy specimens were
      investigated. METHODS: Seventy-five colorectal tumors, 13 polypoid and 62
      nonpolypoid type (56 flat elevated and six depressed type) were studied.
      Proliferating and apoptotic cells were detected with anti-Ki-67 antibody and the
      terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling method,
      respectively. Point mutations at K-ras codon 12 were examined by enriched
      polymerase chain reaction-based restriction fragment length polymorphism assay.
      RESULTS: The average follow-up period was 22 months (range 1-50). The lesions of
      subsequent exophytic growth, unchanged shape, depressed growth, and disappearance
      were observed in 0%, 92%, 0%, and 8% of polypoid type, in 39%, 39%, 13%, and 9%
      of flat elevated type, and in 33%, 67%, 0%, and 0% of depressed type,
      respectively. There was no significant difference in tumor size between initial
      and follow-up colonoscopy. Nonpolypoid tumors apparently changed to the exophytic
      growth during 2 yr or more. The tumors with exophytic growth had significantly
      higher proliferative indices/apoptotic indices ratios than those with unchanged
      morphology and disappearance/depressed growth (p < 0.05, respectively). K-ras
      codon 12 point mutations did not correlate with tumor development. CONCLUSIONS:
      Cell kinetic status plays an important role in determining minute colorectal
      tumor development, but not K-ras codon 12 mutations. Minute nonpolypoid adenomas
      frequently tend to grow slowly, and nearly 40% of those become the exophytic
      growth with time. Most of minute nonpolypoid tumors seem to follow the adenoma
      carcinoma sequence.

PMID- 12190187
TI  - Preliminary observation with dronabinol in patients with intractable pruritus
      secondary to cholestatic liver disease.
AB  - Pruritus due to cholestatic liver disease can be particularly difficult to manage
      and frequently is intractable to a variety of medical therapies. The aim of our
      study is to evaluate the efficacy of delta-9-tetrahydrocannabinol (delta-9-THC)
      for intractable cholestatic related pruritus (ICRP) that has failed conventional
      (and unconventional) remedies. Three patients were evaluated for plasmapheresis
      because of ICRP. All 3 patients had previously been extensively treated with
      standard therapies for ICRP including: diphenhydramine, chlorpheniramine,
      cholestyramine, rifampicin, phenobarbital, doxepin, naltrexone, UV therapy, and
      topical lotions. Even multiple courses of plasmapheresis were performed without
      any benefit for the intractable pruritus. All patients reported significant
      decreases in their quality of life, including lack of sleep, depression,
      inability to work, and suicidal ideations. All patients were started on 5 mg of
      delta-9-THC (Marinol) at bedtime. All 3 patients reported a decrease in pruritus,
      marked improvement in sleep, and eventually were able to return to work.
      Resolution of depression occurred in two of three. Side effects related to the
      drug include one patient experiencing a disturbance in coordination. Marinol
      dosage was decreased to 2.5 mg in this patient with resolution of symptoms. The
      duration of antipruritic effect is approximately 4-6 hrs in all three patients
      suggesting the need for more frequent dosing. Delta-9-tetrahydrocannabinol may be
      an effective alternative in patients with intractable cholestatic pruritus.

PMID- 12190188
TI  - Abnormal distribution of the interstitial cells of cajal in an adult patient with
      pseudo-obstruction and megaduodenum.
AB  - Interstitial cells of Cajal (ICC) are fundamental regulators of GI motility.
      Here, we report the manometrical abnormalities and abnormalities of ICC
      distribution and ultrastructure encountered in a 30-yr-old patient with
      megaduodenum and pseudo-obstruction. Full thickness biopsies taken during
      laparoscopic placement of a jejunostomy showed vacuolated myocytes and fibrosis
      predominantly in the outer third of the circular muscle layer of the duodenum,
      suggestive for visceral myopathy. The distribution of ICC was also strikingly
      abnormal: by light microscopy, ICC surrounding the myenteric plexus were lacking
      in the megaduodenum, whereas ICC were normally present in the duodenal circular
      muscle and in the jejunum. By electron microscopy, very few ICC were identified
      around the duodenal myenteric plexus. These findings suggest that abnormalities
      in ICC may contribute to the disturbed motility in some myopathic forms of
      intestinal pseudo-obstruction.

PMID- 12190189
TI  - Natural history of mucinous ductal ectasia of the pancreas: a case report and
      review of the literature.
AB  - Mucinous ductal ectasia (MDE) remains a less known disease entity of the
      pancreas. In an attempt to further characterize its natural history, we report
      the case of a 68-yr-old man with MDE initially unrecognized in an abdominal CT
      obtained 5 yr before diagnosis and resection. Furthermore, we have reviewed
      available case reports in the English literature to clarify the differences
      between MDE and mucinous cystic neoplasm, two entities that have been frequently
      confused for one another. MDE is an uncommon disorder of the pancreas
      characterized by dilated primary and secondary ducts filled with thick mucus that
      appear as a mass or cyst by ultrasound or CT. ERCP demonstrates a patulous
      duodenal papilla with extruding mucin from the orifice. Histological changes
      within the ducts reveal hyperplasia, adenoma, or adenocarcinoma. The recognition
      of MDE is essential because early detection allows for curative surgical
      resection of these usually latent and indolent pancreatic neoplasms. Further
      characterization of MDE and additional longitudinal studies are necessary to
      elucidate its natural history and define its optimal management.

PMID- 12190190
TI  - New tools for the diagnosis of peritoneal carcinomatosis?

PMID- 12190191
TI  - Combined therapy for secondary prophylaxis of variceal rebleeding?

PMID- 12190192
TI  - Surveillance and surgery for Barrett's esophagus: more results from Sweden.

PMID- 12190193
TI  - Precore stop mutant in anti-HBe-positive phases of chronic hepatitis B virus
      infection.

PMID- 12190194
TI  - Re: Postmarking adverse events related to sotradecol (sodium tetradecyl sulfate
      sclerosing agent).

PMID- 12190195
TI  - Re: Burke et al: positive fecal occult blood test.

PMID- 12190196
TI  - Pelvic abscess after ingestion of blister-wrapped tablet.

PMID- 12190197
TI  - Assessing resection margins using high-magnification chromoscopy: a useful tool
      after colonic endoscopic mucosal resection.

PMID- 12190198
TI  - Gut-liver axis: a new point of attack to treat chronic liver damage?

PMID- 12190199
TI  - Cyclooxygenase-2 expression in the adenoma-carcinoma sequence of human
      gallbladder.

PMID- 12190201
TI  - Mitral valve endocarditis caused by Streptococcus oralis occurring after upper
      gastrointestinal endoscopy.

PMID- 12190200
TI  - Fenofibrate treatment in patients with primary biliary cirrhosis.

PMID- 12190202
TI  - Prevention of radiation-induced diarrhea with the use of VSL#3, a new high
      potency probiotic preparation.

PMID- 12190203
TI  - Severe cholestasis in a patient with acute hepatitis C treated with interferon
      alpha-2b.

PMID- 12190204
TI  - Elastosis perforans serpiginosa secondary to D-penicillamine treatment in a
      Wilson's disease patient.

PMID- 12190205
TI  - Road traffic accident as an iatrogenic complication of steroid treatment in
      Crohn's disease.

PMID- 12190206
TI  - Axillary hidradenitis suppurativa successfully treated with infliximab in a
      Crohn's disease patient.

PMID- 12190207
TI  - Re: Lasso-de-la-Vega et al. gabapentin as a probable cause of hepatotoxicity and
      eosinophilia.

PMID- 12190208
TI  - Heat stroke.

PMID- 12190209
TI  - Gamma-hydroxybutyric acid: a medicine or a drug of abuse?

PMID- 12190210
TI  - Kluver-Bucy syndrome after minor brain injury.

PMID- 12190211
TI  - NHLBI stops trial of estrogen plus progestin due to increased breast cancer risk
      and lack of overall benefit.

PMID- 12190212
TI  - Drug-associated heat stroke.
AB  - During the June 1998 heat wave in New Orleans, 8 patients came to the emergency
      department of a large public hospital over a 14-day period. They were
      subsequently admitted to the intensive care unit with a diagnosis of heat stroke.
      On each of these days, the ambient temperature exceeded 33.3 degrees C (91.9
      degrees F). Although the highest recorded temperature was only 35.6 degrees C (96
      degrees F), the heat index reached a high of 44.5 degrees C (112 degrees F).
      Weather-related heat illnesses are well documented, but the reports rarely
      address contributing medications or drugs. In this series, 6 patients (75%) had
      been using medication or drugs known to induce or worsen hyperthermia. A seventh
      patient had been prescribed a phenothiazine, but actual use could not be
      established. An eighth patient had an unidentified agent detected on toxicologic
      screening. The most common drug identified was cocaine. Other drugs included
      diphenhydramine, tricyclic antidepressants, and phenothiazines. Six patients
      (75%) had rhabdomyolysis; 3 of them also had disseminated intravascular
      coagulation. There were 2 deaths, yielding a 25% mortality rate.

PMID- 12190213
TI  - Comparison of rectal and tympanic thermometry during exercise.
AB  - BACKGROUND: Heat-related deaths are among the most preventable injuries in
      athletics. We sought to examine two methods of monitoring body temperature during
      exercise as a means of preventing heat-related illnesses. METHODS: Ten adult
      subjects exercised in hot, humid conditions while body temperature was monitored
      by rectal (Tre) and tympanic (Tty) thermometry. RESULTS: Our results indicate
      that increase in Tty was significantly greater than increase in Tre during
      exercise. However, rectal temperatures continued to increase after exercise
      cessation and peak temperatures were not significantly different. Temperature
      readings of the two devices during exercise had a strong correlation. There was a
      poor correlation between the two methods of measurement in the recovery phase.
      CONCLUSIONS: Tympanic thermometry is reliable for monitoring changes in body
      temperature during exercise. This could be valuable for monitoring individuals
      during long exercise in an effort to prevent heat exhaustion or heat stoke.

PMID- 12190214
TI  - Impact of medicaid managed care on utilization of obstetric care: evidence from
      TennCare's early years.
AB  - BACKGROUND: TennCare expanded Medicaid coverage, substituting managed care for
      fee-for-service reimbursement in Tennessee. METHODS: To study effects of TennCare
      on utilization of obstetric care (office visits, prenatal tests, care at
      labor/delivery), we used a before (1993) and after (1995) design with North
      Carolina as a control state. Data came from interviews with women with various
      forms of insurance, delivering in 1993 or 1995 in both states. Multivariate
      logistic analysis was used to control for other utilization determinants (eg,
      demographic factors). RESULTS: TennCare women were only 38% as likely to have
      initiated prenatal care during the first trimester as those with traditional
      Medicaid. Ultrasonography and alpha-fetoprotein testing rates were higher for
      TennCare women, and the cesarean section rate was equivalent. However, access to
      care remained lower for TennCare than for the privately insured women.
      CONCLUSIONS: Overall, relative to traditional Medicaid, TennCare did not
      adversely affect access to obstetric care during the program's early years.

PMID- 12190215
TI  - Squamous cell carcinoma of the penis: a retrospective review of forty-five
      patients in northwest Louisiana.
AB  - BACKGROUND: Squamous cell carcinoma of the penis is a rare malignancy in the
      United States, accounting for only 0.4% of all cancers in men. METHODS: From June
      1975 to June 2000, 45 patients were diagnosed and treated for squamous cell
      carcinoma of the penis at our institution. Their medical records were reviewed
      retrospectively. RESULTS: The mean age at diagnosis was 63 years; 62% were white
      and 38% African American. Eighty-nine percent of our population was
      uncircumcised. Twenty patients had primary ilioinguinal lymph node dissections,
      with 11 positive for squamous cell carcinoma. Follow-up was documented for 42
      patients, with a mean of 47 months. Four patients had local penile recurrence at
      a mean of 22 months after initial treatment. Nine patients had died of penile
      carcinoma at a mean of 18 months. CONCLUSION: Squamous cell carcinoma of the
      penis accounts for 0.3% of malignancies in men seen at our institution. Nodal
      metastasis was a poor prognostic indicator. Although local penile recurrence was
      rare (8.8%), patients should be counseled on the importance of self-examination.

PMID- 12190216
TI  - Hepatitis A epidemic in the elderly.
AB  - BACKGROUND: The purpose of this study was to characterize acute hepatitis A in
      patients more than 40 years old. METHODS: Retrospective chart reviews and
      physician questionnaires were used. Hospitalization, laboratory tests, comorbid
      conditions, complications, and mortality were assessed. RESULTS: A total of 180
      cases of acute hepatitis A occurred in patients more than age 40. Hospitalization
      rates increased from 3% for the group aged 40 to 49 to 12% in the group aged 50
      to 69 and 42% in those > or = 70 years old. The mean peak total bilirubin value
      was higher in hospitalized patients than in nonhospitalized patients (12.4 mg/dL
      vs 7.7 mg/dL). Comorbid conditions included significant alcohol consumption (8%),
      diabetes (16.6%), cardiovascular disease (54%), and chronic obstructive pulmonary
      disease (COPD) (21%). Complications included pancreatitis (4.1%), ascites (8.3%),
      prolonged cholestatic features (7.6%), and death (0.8%). CONCLUSION:
      Hospitalization rates and rare complications associated with acute hepatitis A
      increase with age.

PMID- 12190217
TI  - Deaths associated with pregnancy outcome: a record linkage study of low income
      women.
AB  - BACKGROUND: A national study in Finland showed significantly higher death rates
      associated with abortion than with childbirth. Our objective was to examine this
      association using an American population over a longer period. METHODS:
      California Medicaid records for 173,279 women who had an induced abortion or a
      delivery in 1989 were linked to death certificates for 1989 to 1997. RESULTS:
      Compared with women who delivered, those who aborted had a significantly higher
      age-adjusted risk of death from all causes (1.62), from suicide (2.54), and from
      accidents (1.82), as well as a higher relative risk of death from natural causes
      (1.44), including the acquired immunodeficiency syndrome (AIDS) (2.18),
      circulatory diseases (2.87), and cerebrovascular disease (5.46). Results are
      stratified by age and time. CONCLUSIONS: Higher death rates associated with
      abortion persist over time and across socioeconomic boundaries. This may be
      explained by self-destructive tendencies, depression, and other unhealthy
      behavior aggravated by the abortion experience.

PMID- 12190218
TI  - Effect of Helicobacter pylori eradication in the glycemia of children with type 1
      diabetes: a preliminary study.
AB  - BACKGROUND: We previously reported that children with diabetes and Helicobacter
      pylori infection had higher levels of glycated hemoglobin (HbA1c) than uninfected
      peers. We sought to determine whether eradication of the infection could decrease
      their HbA1c level. METHODS: Eight children with type 1 diabetes and H. pylori
      infection (cases) were treated to eradicate the infection. Cases were matched
      (2:1) with uninfected diabetic children (controls), and their HbA1c levels were
      monitored. RESULTS: As previously described, cases started with higher HbA1c
      values than controls. More than 2 years after treatment, cases showed a
      decreasing trend and controls an increasing trend in HbA1c values. At the end of
      the study, cases and controls had comparable HbA1c values. CONCLUSION: These data
      suggest that eradication of H. pylori infection in patients with type 1 diabetes
      might be associated with better control of glycemia.

PMID- 12190219
TI  - Emergency department overcrowding in Florida, New York, and Texas.
AB  - BACKGROUND: This study was done to determine the incidence, causes, and effects
      of overcrowding in emergency departments (EDs) in Florida, New York, and Texas.
      METHODS: Surveys were mailed to a random sample of EDs in Florida, New York, and
      Texas. Questions included census, area population, frequency and causes of
      overcrowding, and impact. Causes of overcrowding were ranked on a 5-point scale.
      RESULTS: A total of 300 surveys were sent, and 210 (70%) were returned.
      Overcrowding was reported in 194 EDs (92%): New York (90%), Florida, (92%), and
      Texas (95%). Causes of ED overcrowding included hospital bed shortage, high
      medical acuity of patients, increasing patient volume, too few examination
      spaces, and shortage of RN staff. Overcrowding resulted in death, permanent
      disability, additional procedures, and increased length of hospitalization.
      CONCLUSION: In this survey of EDs, overcrowding was pervasive. Many factors
      contribute to ED overcrowding. Poor medical outcomes may occur because of
      overcrowding.

PMID- 12190220
TI  - Injuries to tobacco farmers in Kentucky.
AB  - Like all types of farming, raising tobacco has many hazards that may lead to
      injury, disability, or death. Burley tobacco farming is a multistep process that
      is not highly mechanized. An 8-year emergency department surveillance system in
      Kentucky identified 674 injury cases related to the production of burley tobacco.
      Most of the injuries were a result of a fall, cutting and piercing instruments,
      or sprains and strains. More than 90% of the injured patients were treated as
      outpatients, and the average charge for emergency room services was $402 (range,
      $0 to $14,729). One quarter of the patients were uninsured. Injuries to Hispanic
      workers increased over the 8-year period. Estimated hospital charge per acre of
      tobacco produced ranged from $1.28 to $1.74. Low-cost interventions such as
      gloves and chaps could reduce the injuries incurred in burley tobacco farming.

PMID- 12190221
TI  - Displaced plaque in retroperitoneal adenopathy.
AB  - BACKGROUND: This study was designed to determine when to consider incidental
      retroperitoneal masses on the basis of a displaced calcified atheromatous
      abdominal aorta on lateral radiographs. METHODS: We did a retrospective review of
      143 normal abdominal helical computed tomography scans of individuals aged 50
      years and older to measure the distance between the posterior aortic wall and
      anterior cortex of vertebral bodies from T12 through L3. RESULTS: The normal
      abdominal aorta maintains a close relationship to the vertebral column. The
      distance should not be more than 10 mm in men and 7.3 mm in women. CONCLUSION:
      Displacement of aortic calcified atheroma greater than these distances should
      prompt a search for a retroperitoneal mass.

PMID- 12190222
TI  - Simultaneous bilateral rupture of quadriceps tendons: analysis of risk factors
      and associations.
AB  - BACKGROUND: Simultaneous bilateral quadriceps tendon rupture is an uncommon
      injury that is frequently misdiagnosed. It has been associated with multiple
      medical conditions including renal disease, rheumatologic disorders, and
      endocrine disorders. METHODS: All reported cases of simultaneous bilateral
      quadriceps tendon rupture were identified using MEDLINE. Each case was reviewed
      for information regarding the injury, and this information was analyzed. RESULTS:
      There were 66 cases of simultaneous bilateral quadriceps tendon rupture reported
      in the English-language literature. This review presents descriptive data on all
      the cases and analyzes the following factors surrounding rupture: age, sex, time
      before diagnosis, mechanism of injury, location of rupture, and associated
      chronic diseases. Most patients were treated surgically, followed by 4 to 6 weeks
      of immobilization, which resulted in a good outcome. CONCLUSION: Numerous
      associations were found and are discussed in this review. Patients with
      quadriceps tendon rupture should be evaluated for an underlying chronic disease.

PMID- 12190223
TI  - Urinary tract infection as a possible marker for teenage sex.
AB  - BACKGROUND: Pediatric urinary tract infections (UTIs) are markers for
      genitourinary reflux or obstruction. Adult UTIs are treated by telephone triage
      without microbiologic study. The contrast between pediatric and adult UTIs
      prompted our retrospective review of adolescent UTIs. METHODS: Ninety-six
      adolescent girls without chronic illness, urogenital abnormalities, pregnancy,
      enuresis, or constipation had urine cultures with 100,000 colonies/mm3. RESULTS:
      The 32 patients who were initially sexually active continued sexual activity
      (75%), became pregnant (25%), and had subsequent sexually transmitted diseases
      (STDs) (13%). There were no pregnancies, STDs, or subsequent UTIs in 9 patients
      who were not initially sexually active. The 55 patients with no documentation of
      sexual activity were comparable to those who were initially sexually active: 66%
      had evidence of sexual activity; 20% had subsequent pregnancy; 14% had subsequent
      STDs; and 42% had UTI recurrence. CONCLUSION: Adolescents with UTIs have a
      significant frequency of sexual activity. Information about responsible sexual
      activity and access to care is important to adolescents, particularly those with
      UTIs.

PMID- 12190224
TI  - Noninvasive carbon dioxide monitoring during neurosurgical procedures in adults:
      end-tidal versus transcutaneous techniques.
AB  - BACKGROUND: We prospectively compared transcutaneous (TC) versus end-tidal (ET)
      carbon dioxide monitoring during neurosurgical procedures in adults. METHODS:
      After calibration and an equilibration time for the TC-CO2 monitor, arterial
      blood gas (ABG) values were obtained as clinically indicated. The PaCO2 values
      were compared with the values recorded by the noninvasive monitors (TC and ET).
      RESULTS: The ET-CO2 to PaCO2 difference was 6.1 +/- 5.6 mm Hg, and the TC-CO2 to
      PaCO2 difference was 3.7 +/- 2.9 mm Hg. The difference between the PaCO2 and ET
      CO2 was 3 mm Hg or less in 17 of 57 values, while the difference between the
      PaCO2 and TC-CO2 was 3 mm Hg or less in 35 of 57 values. Linear regression
      analysis of ET-CO2 versus PaCO2 revealed a slope of 0.381 +/- 0.007. Linear
      regression analysis of TC-CO2 versus PaCO2 revealed a slope of 1.17 +/- 0.008.
      CONCLUSION: Transcutaneous CO2 monitoring provides a more accurate estimate of
      PaCO2 than ET-CO2 monitoring during neurosurgical procedures.

PMID- 12190225
TI  - Limb amputation and limb deficiency: epidemiology and recent trends in the United
      States.
AB  - BACKGROUND: The purpose of this study was to provide a comprehensive perspective
      on the epidemiology and time trends in the incidence of limb amputations and limb
      deficiency in the United States. METHODS: Data from the Healthcare Cost and
      Utilization Project from 1988 through 1996 were used to calculate rates of
      congenital deficiency, trauma-related, cancer-related, and dysvascular
      amputations in the United States. Trends over time in adjusted rates were then
      examined using linear regression techniques. RESULTS: Dysvascular amputations
      accounted for 82% of limb loss discharges and increased over the period studied.
      Over all years, the estimated increase in the rate of dysvascular amputations was
      27%. Rates of trauma-related and cancer-related amputations both declined by
      approximately half. The incidence of congenital deficiencies remained stable.
      CONCLUSIONS: The risk of amputations increased with age for all causes and was
      highest among blacks having dysvascular amputations. Increasing risk of
      dysvascular amputations, particularly among elderly and minority populations, is
      of concern and warrants further investigation.

PMID- 12190226
TI  - Incidental granulomatous inflammation of the uterus.
AB  - BACKGROUND: Granulomas of the uterine corpus have been reported in a variety of
      pathologic conditions but are relatively rare findings in routine histopathologic
      material. METHODS: This retrospective clinicopathologic study reviewed patients
      diagnosed with uterine granulomas between 1980 and 1999 in a tertiary referral
      center. RESULTS: The study group was comprised of 11 women, ranging in age from
      37 to 90 years. All patients had histologically confirmed, non-necrotizing
      granulomas. The most common symptom prompting biopsy or hysterectomy was abnormal
      bleeding. Several concomittant histopathologies were noted. Eight of 11 patients
      had a known history of uterine instrumentation. None of the patients had clinical
      evidence of sarcoidosis or systemic infection, and stains for microorganisms were
      negative in all cases. Polarizable or foreign materials were not seen.
      CONCLUSIONS: Well-formed, non-necrotizing granulomas are an infrequent finding in
      the uterus. A history of instrumentation may explain the presence of granulomas
      in a subset of patients.

PMID- 12190227
TI  - Anemia of cancer in intermediate-grade non-Hodgkin's lymphoma.
AB  - BACKGROUND: Current literature suggests that anemia at baseline is an important
      adverse prognostic factor for lymphoma-related outcomes. We evaluated the
      prevalence, risk factors, and prognostic value of anemia in patients with
      intermediate-grade non-Hodgkin's lymphoma (IGNHL) treated in a community-based
      practice. METHODS: The retrospective sample included 591 patients who had IGNHL
      diagnosed between 1993 and 1999 and who were subsequently treated with CHOP
      chemotherapy. Anemia was defined as a hemoglobin (Hb) value < 12 g/dL. RESULTS:
      Anemia was present in 193 of 546 patients (35.3%). Baseline anemia was
      significantly associated with age > 60, extranodal sites > or = 2, Ann Arbor
      stage III or IV, elevated lactate dehydrogenase (LDH) level, B symptoms, and
      histology type. Baseline Hb was also a significant predictor of nonresponse to
      chemotherapy. CONCLUSIONS: Our study results support previous findings of a high
      prevalence of anemia in cancer patients before cytotoxic therapy and the adverse
      impact that baseline anemia has on response to chemotherapy.

PMID- 12190228
TI  - Aspergillosis in liver transplant recipients: successful treatment and improved
      survival using a multistep approach.
AB  - BACKGROUND: Invasive aspergillosis is a life-threatening complication in liver
      transplant recipients, with a reported mortality rate of more than 90%. Treatment
      is difficult, and no single agent is uniformly effective in treating this patient
      population. METHODS: We retrospectively reviewed all fungal cultures from 200
      liver transplant patients between 1996 and 1999 at a single tertiary referral
      center. RESULTS: A diagnosis of aspergillosis was made in 6 patients. Five
      patients had pulmonary involvement; 1 presented with an inguinal mass. Time from
      transplant to infection ranged from 1 week to 34 months. Treatment included
      surgical intervention and medical treatment. All patients infected with
      Aspergillus fumigatus were treated with a sequential protocol of lipid complex
      amphotericin followed by itraconazole. The major side effect of treatment was
      worsening renal function. One patient died of intracranial hemorrhage during
      treatment. CONCLUSION: Successful treatment of aspergillosis in liver transplant
      recipients should include early diagnosis, sequential medical treatment with
      lipid amphotericin B and itraconazole, and surgical intervention for invasive
      disease.

PMID- 12190229
TI  - Access to care and stage at diagnosis for patients with lung cancer and
      esophageal cancer: analysis of the Savannah River Region Information System
      cancer registry data.
AB  - BACKGROUND: Disparities have been observed in both the incidences of lung and
      esophageal cancers and the survival of those patients. Our goals were to
      determine if race was associated with stage of cancer at diagnosis, and to
      identify predictors of advanced-stage lung and esophageal cancers. METHODS: All
      cases of lung and esophageal cancer between 1991 and 1995 in the Savannah River
      Region Information System cancer registry were studied. Data were analyzed using
      logistic regression to identify independent predictors of advanced disease at the
      time of diagnosis. RESULTS: Among lung cancer patients, histology and distance to
      nearest hospital predicted diagnosis at an advanced stage. Residence in an area
      with a high proportion of Medicaid recipients was a predictor of advanced stage
      in esophageal cancer patients. CONCLUSIONS: In this predominantly rural area,
      decreased utilization of health services was evident among older, poor, black,
      rural cancer patients. Further investigation involving prospective data
      collection from cancer patients is warranted.

PMID- 12190230
TI  - Breastfeeding rates at an urban medical university after initiation of an
      educational program.
AB  - BACKGROUND: Our objective was to improve breastfeeding initiation rates at an
      urban medical center. METHODS: A breastfeeding educational program for health
      care providers was developed and implemented in 1995. The outcome variable of
      interest was the change in breastfeeding initiation rate during 2 periods, 1993
      1994 and 1996 to 1999, stratified by weight (> 2,000, 1,500 to 2,000, and < 1,500
      g). RESULTS: The breastfeeding initiation rate in 1996 to 1999 for all mothers of
      newborns admitted to the hospital was 47.1% (4,107/8,724), compared with the 1993
      1994 rate of 18.9% (816/4,315). During the second period, the breastfeeding rate
      among mothers of infants < 1,500 g was 60.8% (468/770), compared with 19.2%
      (56/293) during the earlier study period. Stratified by weight, the greatest
      improvement in rates of breastfeeding initiation and at discharge was seen with
      mothers of preterm infants. CONCLUSION: A breastfeeding educational program that
      interfaced with medical staff and mothers at an urban medical university was
      associated with increased rates of breastfeeding initiation.

PMID- 12190231
TI  - Emerging technology in diabetes mellitus: glucose monitoring and new insulins.
AB  - Modern diabetes management requires intensive self-monitoring of blood glucose
      levels, often coupled with a multicomponent insulin program. Recent advances
      include alternate site blood glucose testing devices, which facilitate more
      frequent sampling by individuals with diabetes. Continuous glucose monitoring
      through interstitial fluid analysis is now available and appears to give a more
      representative picture of the glycemic variations typical for type 1 diabetes.
      Recombinant DNA technology has led to the development of new insulin analogs that
      provide more physiologic insulin delivery. Inhaled and oral insulin formulations
      may replace multiple injections in future insulin therapy regimens.

PMID- 12190232
TI  - Thoracoscopic management of pleural effusions in Kaposi's sarcoma: a rapid and
      effective alternative for diagnosis and treatment.
AB  - Kaposi's sarcoma (KS) is one of the most common causes of pleural effusion in
      patients with acquired immunodeficiency syndrome (AIDS). Pleural effusions due to
      KS carry a high morbidity and mortality. Their treatment is difficult, and they
      respond poorly to chemical pleurodesis. Even systemic chemotherapy against KS has
      little effect on the pleural effusions. Commonly, repeated therapeutic
      thoracentesis or chest tube drainage is required. We present a case of advanced
      KS with bilateral pleural effusions. We believe this is the first reported case
      in which medical thoracoscopy with talc pleurodesis has been shown to achieve
      adequate control of the effusions.

PMID- 12190233
TI  - Metastatic breast cancer manifested as refractory anemia and gastric polyps.
AB  - Gastric metastasis from breast cancer is uncommon and typically occurs in
      patients with disseminated disease. The vast majority of patients with gastric
      lesions have a known preexisting diagnosis of breast cancer. In contrast, we
      describe a case in which a minimal breast cancer was found to be the primary
      tumor during the workup of a patient first diagnosed with carcinoma of unknown
      primary and subsequently presumed to have metastatic gastric cancer. Our case
      illustrates that a diagnosis of breast cancer metastatic to the stomach may
      require a high index of suspicion, as well as a meticulous breast workup. It also
      emphasizes that even tiny breast cancers have a small but real risk of metastatic
      spread. Determination of the correct primary source in these cases may not be
      only an academic exercise, since the treatment and prognosis of metastatic breast
      cancer (especially receptor positive) and metastatic gastric cancer are
      different.

PMID- 12190234
TI  - Self-medication with gamma-hydroxybutyrate to reduce alcohol intake.
AB  - We describe a 52-year-old man who self-medicated with gamma-hydroxybutyrate
      (GHB), a widely available illicit substance, to obtain a decrease in ethanol
      consumption. He successfully reduced his ethanol intake over a 3-month period,
      but he was unable to sustain abstinence. Although case reports on the use of GHB
      to induce euphoria have been published, this is the first report of GHB self
      medication to facilitate ethanol abstinence. This report highlights the
      importance of considering GHB self-medication not only for euphoric and mood
      altering effects, but also as a potential treatment for ethanol intake reduction.

PMID- 12190235
TI  - Kluver-Bucy syndrome as a result of minor head trauma.
AB  - Kluver-Bucy syndrome (KBS) has been described as a disconnection of the temporal
      lobes from the remainder of the brain. Its presence in minor head trauma has not
      been previously reported. We therefore report what we believe to be the first
      case of KBS due to mild head trauma and unilateral injury to a temporal lobe.

PMID- 12190236
TI  - Herniated nucleus pulposus with radiculopathy in an adolescent: successful
      nonoperative treatment.
AB  - The following report describes a 17-year old girl with a central herniated
      nucleus pulposus (HNP) at L4-5. The diagnosis of lumbar disk herniation was based
      on findings from magnetic resonance imaging (MRI). A decision to use conservative
      treatment was unanimously agreed upon by a team of orthopedists, a neurosurgeon,
      and an internist. This report follows the patient's course from the onset of pain
      through the completion of the nonoperative treatment and shows that HNP of a
      lumbar intervertebral disk with radiculopathy can be treated successfully with
      aggressive nonoperative care.

PMID- 12190237
TI  - HELLP syndrome leading to a diagnosis of pregnancy.
AB  - HELLP syndrome (an acronym for hemolysis, elevated liver enzymes, and low
      platelets) is a life-threatening complication of pregnancy seen in association
      with either preeclampsia or eclampsia. HELLP syndrome is rarely diagnosed before
      24 weeks of gestation. This atypical form of severe preeclampsia is associated
      with significant fetal and maternal mortality. The only effective treatment is
      delivery. We report a case of HELLP syndrome that proved to be a diagnostic clue
      to an early pregnancy.

PMID- 12190239
TI  - Coexisting Gilbert's syndrome and sickle cell disease.
AB  - We report the coexistence of Gilbert's syndrome and homozygous sickle cell
      disease in a child with persistent unconjugated hyperbilirubinemia.

PMID- 12190240
TI  - Primary splenic lymphoma complicated by hematemesis and gastric erosion.
AB  - Gastrosplenic fistula resulting from erosion of a primary splenic lymphoma is a
      rare cause of massive upper gastrointestinal hemorrhage associated with benign
      peptic ulcer disease, gastric Crohn's disease, gastric adenocarcinoma, and
      primary gastric and splenic lymphomas. Upper intestinal hemorrhage can be
      successfully treated with splenic artery embolization, followed by splenectory
      and gastric resection.

PMID- 12190238
TI  - Hemothorax and retroperitoneal hematoma after anticoagulation with enoxaparin.
AB  - A 58-year-old woman with chronic obstructive pulmonary disease had spontaneous
      bilateral hemothorax and a retroperitoneal hematoma after 4 days of
      anticoagulation therapy with enoxaparin (1 mg/kg subcutaneously every 12 hours)
      for suspected pulmonary thromboembolism. The patient was successfully managed
      with red blood cell and plasma transfusions, multiple thoracenteses for
      evacuation of blood from the pleural space, short-term mechanical ventilation,
      and administration of bronchodilators, corticosteroids, and antibiotics. This is
      the first report of spontaneous hemothorax and the third report of spontaneous
      retroperitoneal hematoma associated with enoxaparin therapy.

PMID- 12190241
TI  - Long-term survival of a patient with human immunodeficiency virus infection and
      Hodgkin's lymphoma.
AB  - When patients infected with human immunodeficiency virus (HIV) are found to have
      Hodgkin's lymphoma (HL), it is generally advanced, with involvement of extranodal
      sites including bone marrow, spleen, and liver, and prognosis tends to be
      unfavorable. We present the case of a 38-year-old white man who had HIV and HL
      diagnosed in 1990. Despite presenting with stage IV HL, having recurrence of HL
      after initially attaining remission, and being hospitalized on several occasions
      for opportunistic infections, he ultimately achieved complete remission of HL and
      is alive 9 years after initial diagnosis. This case illustrates that although
      unusual, prolonged survival of an HIV-infected patient with HL associated with
      poor prognostic features is possible.

PMID- 12190242
TI  - Successful treatment of cryptococcal osteomyelitis and paraspinous abscess.

PMID- 12190243
TI  - Medicine and the sin tax.

PMID- 12190244
TI  - Informed consent for circumcision.

PMID- 12190245
TI  - Treatment of retroperitoneal fibrosis with tamoxifen.

PMID- 12190246
TI  - Fatal granulomatous bronchopneumonia complicated by acute renal failure.

PMID- 12190247
TI  - Relapsing group B streptococcal bacteremia.

PMID- 12190248
TI  - Body tilt effect on the reproduction of orientations: studies on the visual
      oblique effect and subjective orientations.
AB  - Body tilt effects on the visual reproduction of orientations and the Class 2
      oblique effect (E. A. Essock, 1980) were examined. Body tilts indicate whether
      the oblique effect (i.e., lower performance in oblique orientations than in
      vertical-horizontal orientations) is defined in an egocentric or a gravitational
      reference frame. Results showed that the oblique effect observed in upright
      posture disappeared in tilted conditions, mainly due to a decrease in the
      precision of the vertical and horizontal settings. In tilted conditions, the
      subjective visual vertical proved to be the orientation reproduced the most
      precisely. Thus, the oblique effect seemed to be not purely gravitationally or
      egocentrically defined but, rather, to depend on a subjective gravitational
      reference frame tilted in the same direction as body tilts.

PMID- 12190249
TI  - Garner and congruence effects in the speeded classification of bimodal signals.
AB  - The role of attention in speeded Garner classification of concurrently presented
      auditory and visual signals was examined in 4 experiments. Within-trial
      interference (i.e., congruence effects) occurred regardless of the attentional
      demands of the task. Between-trials interference (i.e., Garner interference)
      occurred only under conditions of divided attention when making judgments about
      auditory signals. Of importance, the data show congruence effects in the absence
      of Garner interference. Such a pattern has been rarely reported in studies of the
      classification of purely visual stimuli and contradicts theoretical accounts
      asserting that the effects share a common locus. The data question the notion
      that Garner classification reveals fundamental insights about the nature of the
      perceptual processing of bimodal stimuli.

PMID- 12190250
TI  - Coordination dynamics of learning and transfer across different effector systems.
AB  - If different effector systems share a common task-specific coordination dynamics,
      transfer and generalization of sensorimotor learning are predicted. Subjects
      learned a visually specified phase relationship with either the arms or the legs.
      Coordination tendencies in both effector systems were evaluated before and after
      practice to detect attractive states of the coordination dynamics. Results
      indicated that learning a novel relative phase with a single effector system
      spontaneously transferred to the other, untrained effector system. Transfer was
      revealed not only as improvements in performance but also as modifications of
      each system's initial (prelearning) coordinative landscape. What is learned,
      appears to be a high-level but neurally instantiated dynamic representation of
      skilled behavior that proves to be largely effector independent, at least across
      anatomically symmetric limbs.

PMID- 12190252
TI  - Temporal integration in structure from motion.
AB  - A temporal integration model is proposed that predicts the results reported in 4
      psychophysical experiments. The main findings were (a) the initial part of a
      structure-from-motion (SFM) sequence influences the orientation evoked by the
      final part of that sequence (an effect lasting for more than 1 s), and (b) for
      oscillating SFM sequences, perceived slant is affected by the oscillation
      frequency and by the sign of the final gradient. For contracting optic flows
      (i.e., rotations away from the image plane), the sequence with the lowest
      oscillation frequency appeared more slanted; for expanding optic flows (i.e.,
      rotations toward the image plane), the sequence with the highest oscillation
      frequency appeared more slanted.

PMID- 12190251
TI  - The siren song of implicit change detection.
AB  - Although change blindness could suggest that observers represent far less of
      their visual world than their conscious experience leads them to believe, they
      could fail to detect changes even if they fully represent all details. Reports of
      implicit change detection in the absence of awareness are consistent with the
      notion that observers' representations are more complete than previously thought.
      However, to provide convincing evidence, studies must separate implicit detection
      from explicit processes. This article reexamines the 3 primary claims of implicit
      change detection and, after replicating original findings, provides theoretical
      and empirical support for alternative, explicit explanations. Even if observers
      do represent more of the scene than previously thought, change detection might
      occur only through explicit comparisons.

PMID- 12190253
TI  - No negative semantic priming from unconscious flanker words in sight.
AB  - In replicating 1 of the within-language conditions of E. Fox's (1996) Experiment
      1, the authors confirmed that unattended words presented 2.4 degrees above and
      below fixation are mostly unavailable to awareness. However, no negative semantic
      priming was observed in a lexical decision on a probe letter string appearing
      about 1 s later, which does not replicate Fox's finding. These results are
      compatible with the hypothesis underlying the present study, according to which
      positive semantic priming, if any, rather than negative semantic priming is
      expected in Fox's situation. The reason is that unavailability to awareness of
      the parafoveal words is not achieved by means of an act of selective inhibition
      combined with attentional diversion through masking but is achieved simply by
      means of perceptual degradation.

PMID- 12190254
TI  - Perceptual integrality of sex and identity of faces: further evidence for the
      single-route hypothesis.
AB  - According to current face-recognition models, sex (gender) and identity of faces
      are processed in independent routes. Using Garner's speeded-classification task,
      the authors provide evidence that sex and identity are processed within a single
      route. In 4 experiments, participants judged the sex or the familiarity of faces
      while the other dimension remained constant or varied randomly. The results of
      Experiments 1, 2, and 4 showed that participants could not selectively attend to
      either sex or familiarity without being influenced by the other, irrelevant
      dimension. Thus, identity and sex are integral dimensions. Experiment 3 provided
      evidence that when sex judgments are based on hairstyle heuristics, false
      separability can emerge. The findings support the claim that identity and sex are
      processed within a single route.

PMID- 12190255
TI  - Transsaccadic perception of saccade target and flanker objects.
AB  - To account for location-dependent and location-independent preview benefits in
      transsaccadic object perception, J. M. Henderson (1994) and J. M. Henderson and
      M. D. Anes (1994) proposed a dual-route model in which both episodic object
      representations and long-term memory representations store information across a
      saccade. Four experiments are reported in which the dual-route model was
      assessed. Preview benefits for saccade target objects were found to be location
      independent, whereas preview benefits for flanker objects were location
      dependent. These results support a single-route, 2-stage model of transsaccadic
      object perception. First, preattentive object files are set up to parse a set of
      attentional and/or saccade targets from peripheral vision, causing location
      dependent preview benefits. Second, 1 object is attentionally selected for
      further processing, activating long-term memory representations and resulting in
      location-independent preview benefits.

PMID- 12190256
TI  - The roles of static depth information and object-image relative motion in
      perception of heading.
AB  - In a series of 6 experiments, two hypotheses were tested: that nominal heading
      perception is determined by the relative motion of images of objects positioned
      at different depths (R. F. Wang & J. E. Cutting, 1999) and that static depth
      information contributes to this determination. By manipulating static depth
      information while holding retinal-image motion constant during simulated self
      movement, the authors found that static depth information played a role in
      determining perceived heading. Some support was also found for the involvement of
      R. F. Wang and J. E. Cutting's (1999) categories of object-image relative motion
      in determining perceived heading. However, results suggested an unexpected
      functional dominance of information about heading relative to apparently near
      objects.

PMID- 12190257
TI  - Stimulus-driven and goal-driven control over visual selection.
AB  - This article explored the extent to which stimulus-driven control over visual
      selection is modulated by goal-driven factors. Observers searched for a no-onset
      color target among 3 distractors and signaled its location either manually or
      with a saccade. Additional distractors appeared either with or without an abrupt
      onset and were either similar or dissimilar to the target. Abrupt onsets
      disrupted saccades to the target, especially when they shared the target color.
      Irrelevant onsets also interfered with the manual responses, but this
      interference was dependent on the particular type of manual response. Stimulus
      driven and contingent capture can occur within a single paradigm, but the extent
      and nature of these effects depend on the specific response required.

PMID- 12190259
TI  - Role of structure and component in judgments of visual similarity of Chinese
      characters.
AB  - Skilled readers of Chinese participated in sorting and visual search experiments.
      The sorting results showed that under conditions of conflicting information about
      structure and component, subjective judgments of the visual similarity among
      characters were based on the characters' overall configurations (i.e.,
      structures) rather than on the common components the characters possessed. In
      visual search, both structure and component contributed to the visual similarity
      reflected by the search efficiency. The steepest search slopes (thus the most
      similar target-distractor pairs) were found when the target and the distractor
      characters had the same structure and shared 1 common component, compared with
      when they had different structures and/or shared no common components. Results
      demonstrated that character structure plays a greater role in the visual
      similarity of Chinese characters than has been considered.

PMID- 12190258
TI  - Empirical evidence for independent dimensions in the visual representation of
      three-dimensional shape.
AB  - Three experiments investigated whether the human visual system can make
      independent estimations of 3-dimensional shape dimensions, as suggested by
      structural description models of human object recognition. Experiment 1 used a
      noise masking paradigm to investigate whether primary-axis curvature and aspect
      ratio are estimated independently. The results showed clear evidence that these 3
      dimensional shape properties are estimated independently from the image.
      Experiment 2 investigated whether the visual system can treat any arbitrary set
      of independent shape dimensions independently. The dimensions used in Experiment
      2 were linear combinations of aspect ratio and primary-axis curvature used in
      Experiment 1. Experiment 2 results showed that these 2 dimensions were not
      estimated independently. Using the same masking paradigm, Experiment 3
      investigated whether an object's 3-dimensional shape is estimated independently
      of the object's viewpoint. This experiment found that shape properties are
      estimated independently of viewpoint.

PMID- 12190260
TI  - Effects of lexicality and distinctiveness on repetition blindness.
AB  - The repetition blindness (RB) paradigm developed by K. M. Arnell and P. Jolicoeur
      (1997) was used to examine effects of lexicality (word vs. nonword target pairs)
      and target distinctiveness on RB. Distinctiveness was manipulated by having both
      targets (Experiments 1 and 2) or only the first target (Experiment 3) brighter
      than nontarget items. All 3 experiments demonstrated strong RB for word targets
      but no RB for nonword targets. This confirms that RB depends on pre-existing
      memory representations. In fact, there was repetition facilitation for nonwords
      in Experiments 2 and 3. These experiments also demonstrated that RB is reduced
      when targets are distinctive. This finding is better understood interms of RB as
      a failure of memory rather than as a failure of perception.

PMID- 12190261
TI  - Misconceptions about incline speed for nonlinear slopes.
AB  - In 3 experiments, college students provided qualitative predictions about a
      marble's speed along nonlinear inclines. When predicting the outcome of a race
      between identical marbles along differently shaped ramps, most students predicted
      incorrectly that the shorter path was necessarily quicker (the shorter-quicker
      belief). When comparing instantaneous speed at 2 points, most students predicted
      incorrectly that incline speed depended on the slope at that point (the slope
      speed belief). A final experiment provides evidence that the slope-speed belief
      reflects a deeper fallacy regarding the resistance encountered while traversing
      inclines and lifting objects. This fallacy also predicts the prevalent belief
      that heavier objects fall faster than lighter objects during incline descent or
      free fall.

PMID- 12190262
TI  - Building phonotactic knowledge in bilinguals: role of early exposure.
AB  - Timing and amount of exposure to a 2nd language in the acquisition of phonotactic
      restrictions was examined in 4 experiments. In Experiments 1 and 2, 10-month-old
      monolingual and bilingual Catalan-Spanish infants were presented with nonwords
      that were phonotactically legal or illegal in Catalan and phonotactically illegal
      in Spanish. Differences between the 4 groups of infants were obtained as a
      function of language dominance. In Experiments 3 and 4, adult Spanish-Catalan
      bilinguals were compared with the same materials. Catalan-dominant bilinguals
      were more accurate than Spanish-dominant bilinguals in their perception of legal
      sequences; however, they were not more accurate with illegal sequences. The
      findings suggest a complex correlation between the pattern of preference and the
      amount and timing of exposure.

PMID- 12190263
TI  - Cross-language computational investigation of the length effect in reading aloud.
AB  - The authors examined whether 2 computational models of reading, the dual-route
      cascaded model (M. Coltheart, K. Rastle, C. Perry, R. Langdon, & J. C. Ziegler,
      2001) and the connectionist 2-layer model (M. Zorzi, G. Houghton, & B.
      Butterworth, 1998), were able to predict the pattern that the length effect found
      in reading aloud is larger in German than in English (J. C. Ziegler, C. Perry, A.
      M. Jacobs, & M. Braun, 2001). The results showed that the dual-route cascaded
      model, which uses a serial mechanism for assembling phonology, successfully
      predicted this cross-language difference. In contrast, the connectionist model of
      Zorzi et al. (1998) predicted the opposite: a larger length effect in English
      than in German. Both the success of one model and the failure of the other
      highlight fundamental differences between 2 major classes of computational
      models.

PMID- 12190264
TI  - Vocabularies of motive for illicit steroid use among bodybuilders.
AB  - Illicit steroid use, for purposes of performance and physique enhancement, is
      widely deemed unnecessary, wrong and dangerous. Such activity would appear
      especially foolhardy when engaged in by non-professional athletes who otherwise
      adhere to 'healthy' exercise regimens. Here a gap exists between many illicit
      steroid users' actions and societal expectations. Using qualitative data
      generated in South Wales, this paper explores bodybuilders' vocabularies of
      motive for illicit steroid use. These accounts which justified, rather than
      excused, steroid use were predominant during question situations between the
      participant observer and the researched. In supporting the fundamental tenets of
      their drug subculture, and as part of the underlying negotiation of self
      identity, respondents espoused three main justifications for their own and/or
      other bodybuilders' illicit steroid use; namely: self-fulfilment accounts,
      condemnation of condemners and a denial of injury. Here steroid use was
      rationalised as a legitimate means to an end, observers passing negative
      judgements were rejected and it was claimed steroids do not (seriously) harm the
      user's health or threaten society more generally. These vocabularies of motive,
      acquired and honoured within bodybuilding settings, comprise a complex of
      subjective meanings which seem to the actor to be an adequate ground for the
      conduct in question. Similar to other sociological studies, this paper states
      that it is imperative to explore the social meanings which illicit drug users
      attach to their 'risk' practices. Without these understandings, researchers and
      health promoters may struggle to appreciate fully why illicit drug users behave
      as they do.

PMID- 12190266
TI  - Bad news from the patient's perspective: an analysis of the written narratives of
      newly diagnosed cancer patients.
AB  - Papers in clinical journals dealing with how to tell cancer patients bad news
      rely mostly on the opinion of the physician. The purpose of the present study was
      to contribute with knowledge from the patient's perspective by analysing how
      patients with recently diagnosed cancer narrate the manner in which they received
      their diagnosis. A consecutive series of 187 patients who had received their
      cancer diagnosis 2-8 months prior to the outset of this study were asked to
      describe the manner in which they learned of their diagnosis in writing. A
      crucial finding from the submitted 138 written narratives was that the
      participants often described experiences from the first contact with hospital
      staff to the end of their treatment, rather than as a single instance of
      diagnosis communication. The relational meaning of these experiences was obvious.
      Information on treatment was of the utmost significance. No one required more
      prognostic information. From the perspective of the physicians, "bad news"
      focuses on how to provide information about diagnosis and prognosis in the course
      of a single diagnostic consultation. From the patient's perspective, "bad news"
      reflects the process of being diseased by cancer, and how medical services are
      available when one is in need of establishing a helpful relationship. In this
      relationship information about diagnosis and treatment is more a means than an
      end.

PMID- 12190265
TI  - "Why don't they just tell me straight, why allocate it?" The struggle to make
      sense of participating in a randomised controlled trial.
AB  - Randomised controlled trials are the acknowledged 'gold standard' method of
      evaluating the effectiveness of treatments, but little is known about how and why
      patients decide to participate in trials nor how much they understand about trial
      design. In this study, in-depth, semi-structured interviews were carried out with
      33 middle aged and older men with lower urinary tract symptoms related to benign
      prostatic disease, 22 of whom had consented to participate and 11 refused to take
      part in a randomised trial. The trial was evaluating the effectiveness of a new
      technology (laser therapy) compared with standard surgery (transurethral
      resection of the prostate ) and conservative management (monitoring without
      active intervention) (the CLasP study). Purposive sampling was used to include
      participants from different centres, each treatment arm, and at different stages
      in participation, as well as those indicated to have refused participation.
      Interviews explored their recall and understanding of trial information, and
      their reasoning about how they were allocated to a treatment. Data were analysed
      thematically according to the methods of constant comparison, and by examining
      each participant's narrative of their experiences. Most participants recalled
      major aspects of trial design, including the involvement of chance, but the case
      studies showed that most also held other co-existing (and sometimes
      contradictory) views about their treatment allocation. The key to understanding
      their experiences was their engagement in a struggle to understand the trial in
      the context of their own beliefs, their recall of the study information and their
      actual experiences of the trial. The outcome of the struggle was the placing of
      trust in clinicians or the development of distrust. Non-participants made sense
      of their experiences in similar ways, but gave different reasons for non
      participation than indicated by recruiters. This study shows that most eligible
      patients, whatever their level of knowledge, will struggle to make sense of their
      participation in randomised trials. The provision of clearer written information
      or time to discuss the trial with particular individuals might be beneficial,
      although greater public understanding of trials is also needed.

PMID- 12190267
TI  - Medical dominance in Italy: a partial decline.
AB  - In the last three decades, a number of changes in health systems has been
      challenging medical dominance in many countries. It has been widely debated
      whether the medical profession has been able to cope with these changes and
      maintain its power or, rather, has been deprofessionalised or proletarianised. In
      this paper, the effects of these changes in Italy are examined, by using a multi
      dimensional concept of medical dominance. As a result of this analysis. medical
      dominance in Italy is depicted as declining on some dimensions while changing its
      nature on others. The final part of the paper discusses some current explanations
      of this trend and suggests that the transition to post-modern society and the
      "late modernity" argument (Giddens, 1990; The consequences of modernity, Polity
      Press, Cambridge; Beck, 1992; Risk society: towards a new modernity, Sage,
      London) may provide an entry into more adequate explanations.

PMID- 12190268
TI  - Too many choices? Hospital and community staff reflect on the future of prenatal
      screening.
AB  - Promoting informed choice is commonly recognised as the chief purpose and benefit
      of prenatal screening, its very presence being viewed as a key way in which the
      process can be distanced from eugenics. As the number of conditions and features
      which can potentially be screened for rises, dilemmas about how to achieve
      informed choice can only increase. Seventy hospital and community staff working
      in or attached to two English hospitals were interviewed individually on topics
      which included their views on genetic developments and moral beliefs and values,
      and how these affected their daily work. The majority then took part in small
      discussion groups led by an ethicist. The research identified a paradox. On the
      one hand, participants recognised the centrality of informed choice to prenatal
      screening, although they had many doubts about whether it could be achieved. On
      the other hand, most saw the expansion of screening, which might further
      compromise informed choice, as an inevitable and inexorable process over which
      they had little, if any, control. This was despite the fact that many of them
      decided, managed or implemented prenatal screening policies within their
      hospitals. The paper explores the factors which staff themselves identified as
      responsible for this perceived inevitable expansion. It then discusses more
      generally how the expansion of medical technologies can appear as inexorable to
      those involved. Finally, the paper calls for more inclusive, integrated and
      collaborative debate and research around the whole area of prenatal screening.
      This is to ensure that as far as possible, the wider consequences and
      implications of any proposed expansion to prenatal screening-both the promises
      and the potential side-effects-are debated ahead of their implementation, and
      also to help ensure that public policy represents and serves contemporary
      society.

PMID- 12190269
TI  - An analysis of private health insurance purchasing decisions with national health
      insurance in Taiwan.
AB  - The Taiwanese health insurance industry is just over 30 years old. Originally
      private and domestic, the industry underwent substantial institutional changes
      when it opened to foreign competition between 1987 and 1994 and when the
      Taiwanese government established national health insurance (NHI) coverage in
      1995. Congruent with these changes, rapid growth occurred in the Taiwanese demand
      for private health insurance. In order to better understand the recent
      performance of the Taiwanese health insurance industry, the structure of the NHI
      system is described and then household decisions to purchase private health
      insurance are analyzed using a two-part (hurdle) model on 1998 Survey of Family
      Income and Expenditure data. Logistic and OLS regressions are used to examine the
      factors influencing the probability and amount of private health insurance
      purchased. Generally, factors affecting the probability of having insurance also
      influence the amount of insurance coverage purchased. Higher income and education
      levels are associated with increased probabilities and larger quantities of
      private insurance purchases. Married females, the employed, and household heads
      working in state-run enterprises are more likely to purchase private insurance
      than their counterparts. The probability of private insurance purchases varies by
      region, with northern Taiwanese households having higher odds of owning private
      insurance than non-northern households. Compared to those in rural villages,
      households in cities and towns are more likely to have private insurance. The
      likelihood of private insurance purchase also tends to rise with advancing age
      and larger family sizes. In addition, one important implication in the private
      health insurance market is highlighted. There is no complementarity between the
      public and private systems.

PMID- 12190270
TI  - Gender, family, and the nutritional status of children in three culturally
      contrasting states of India.
AB  - This paper has three main aims: to measure the clustering of children with low
      weight for age z-scores within families, to establish whether significant
      differences exist by gender in weight for age z-scores, and to demonstrate
      whether the presence of a mother-in-law in the household has any significant
      impact on the nutritional status of young children. Regression modelling is used
      to examine the weight for age z-scores of children under the age of four years in
      Maharashtra, Tamil Nadu and Uttar Pradesh using the 1992-93 Indian National
      Family Health Survey data. Random effects models measure the clustering of
      children with low weight for age z-scores in families, controlling for a number
      of other family factors. Our findings do not reveal significant gender
      differences in weight for age z-scores. Although little variation was found
      between family structures in the nutritional status of children, there were
      significant differences between families after controlling for family type. This
      suggests that there are differences between families that cannot be explained by
      a cross-sectional demographic survey. The evidence from this work suggests that
      nutrition programs need to adopt community nutrition interventions that aim
      resources at young children from families where children with low weight for age
      z-scores are found to cluster. However, there is a need for further inter
      disciplinary research to collect data from families on behavioural factors and
      resource allocation in order that we might better understand why some families
      are more prone to having children with low weight for age z-scores. The diversity
      in the significant covariates between the three states in the models has shown
      the need for Indian nutrition programs to adopt state-specific approaches to
      tackling malnutrition.

PMID- 12190271
TI  - Alcohol mortality: a comparison of spatial clustering methods.
AB  - The identification of spatial clusters of alcohol mortality can be a key tool in
      identifying locations that are suffering from alcohol-related problems or are at
      risk of experiencing those types of problems. This study compares two methods for
      identifying statistically significant spatial clusters of county-level alcohol
      mortality rates in New York. One method utilizes a local indicator of spatial
      association to determine which groups of neighboring counties have rates that are
      significantly related to each other. The other method is a spatial scan technique
      that calculates a maximum likelihood ratio of cases relative to the underlying
      population to identify the group of counties that rejects the null hypothesis of
      "no clustering". The results show that because each technique bases its cluster
      detection on its own criteria, different counties are selected by each method.
      However, the overlap of the selections indicates that the two analytic methods
      illustrate different elements of the same clusters. Consequently, these spatial
      analytic techniques are seen as complimentary and are best used in tandem rather
      than individually. These findings suggest that multiple methods are a preferred
      approach to identifying clusters of alcohol-related mortality at the county
      level.

PMID- 12190272
TI  - Risking risk: the influence of types of capital and social networks on the
      injection practices of drug users.
AB  - Although syringe exchange and other harm reduction interventions have generally
      been effective in reducing bloodborne pathogen incidence among injection drug
      users (IDUs), in some cases a minority of IDUs continues to engage in risky
      injection behavior. Building on emerging perspectives in social epidemiology and
      research on drug use in anthropology that point to the importance of examining
      fundamental social causes of risk behavior, or what puts individuals at risk for
      risk, this study used a multilevel perspective to explore whether forms of
      capital, social network characteristics, and other contextual factors influence
      continued risky injection behavior. Quantitative and qualitative data were
      collected on IDUs in the city of Marseilles, France, where sterile injection
      equipment has been legal and officially promoted since 1995. In multivariate
      analysis on data concerning active users, location in the densest part of a
      large, interconnected network of IDUs greatly increased the likelihood of risky
      injection practices, while there was a non-significant tendency for low Acquired
      Cultural and Economic Capital to predict this behavior. Among the strongest
      individual-level characteristics to predict this outcome were illicit use of
      prescribed medication, generally high dose buprenorphine, and unprotected sex.
      Parental abuse of psychoactive drugs during the subject's childhood, on the other
      hand, greatly decreased the chances of engaging in risky injection behavior.
      Additionally, qualitative data analysis suggests that risky injection may be
      linked to lack of resources to procure drugs, and not simply to inadequate
      sterile injection equipment. Further research, including ecological models, is
      needed to better understand how fundamental social conditions are related to
      "risk for risk". However, public health interventions can already address the
      need for community-level interventions, while rethinking the consequences of
      inaccessible drugs and unintended "leakage" from the introduction of
      buprenorphine and other medicalized treatments for opiate dependency.

PMID- 12190273
TI  - Is low self-esteem an inevitable consequence of stigma? An example from women
      with chronic mental health problems.
AB  - It is often assumed that membership in a stigmatized group has negative
      consequences for the self-concept. However, this relationship is neither
      straightforward nor inevitable, and there is evidence suggesting that negative
      consequences may not necessarily occur (Psychol. Rev. 96(4) (1989) 608). This
      paper argues that the relationship has not been sufficiently theorized, and that
      a more detailed analysis is called for in order to understand the relationship
      between stigma and the self. The paper presents a critical examination of
      modified labeling theory (Am. Sociol. Rev. 52 (1987) 96), with examples from a
      study examining perceptions of stigma and their relationship to self-evaluation
      in women with chronic mental health problems. Open-ended interviews and
      qualitative analyses were used in preference to global measures of self-esteem.
      It was found that although the women were aware of society's unfavorable
      representations of mental illness, and the effects this had on their lives, they
      did not accept these representations as valid and therefore rejected them as
      applicable to the self. The participants did not deny their mental health
      problems, but their acceptance of labels was critical and pragmatic. Labels were
      rejected when they were perceived as carrying an unrealistic and negative
      stereotype, or when the women felt that their symptoms did not fit with the
      diagnostic criteria. The research illustrates the importance of considering
      people's subjective understandings of stigmatized conditions and societal
      reactions in order to understand the relation between stigma and the self.

PMID- 12190274
TI  - Cultural stereotypes of women from South Asian communities: mental health care
      professionals' explanations for patterns of suicide and depression.
AB  - Low rates of treated depression and high rates of suicide in women from some
      South Asian communities are evident in epidemiological studies in the UK. It is
      argued here that explanations for these apparent differences are likely to be
      located in stereotypes of repressive South Asian cultures. This small scale
      study, utilising focus groups and individual interviews, sought to explore the
      construction of cultural stereotypes within mental health discourse with specific
      reference to stereotypes of women from South Asian communities. Mental health
      carers from a UK inner city area of relatively high social deprivation were
      targeted. Focus groups were conducted with a range of mental health care
      professionals who worked in both inpatient and outpatient mental health care
      services. In addition, individual interviews were conducted with consultant
      psychiatrists and General Practitioners. Extensive reference is made in this
      paper to the content of focus groups and interviews and how health carer's
      knowledge about and experience of South Asian cultures and caring for women from
      these communities was contextualised. Mental health care professionals
      constructed cultural difference in terms of fixed and immutable categories which
      operated to inferiorise Britain's South Asian communities. It is argued that
      their knowledge is constructed upon stereotypes of western culture as superior to
      a construction of eastern cultures as repressive, patriarchal and inferior to a
      western cultural ideal. Ultimately, it is argued that these stereotypes become
      incorporated as 'fact' and have the potential to misdirect diagnosis and
      therefore, also misdirect treatment pathways.

PMID- 12190275
TI  - Social variation in self-rated health in Estonia: a cross-sectional study.
AB  - Over the past 40 years Estonia has experienced similar developments in mortality
      to other former Soviet countries. The stagnation in overall mortality has been
      caused mainly by increasing adult mortality. However, less is known about the
      social variation in health. This study examines differences in self-rated health
      by eight main dimensions of the social structure on the basis of the Estonian
      Health Interview Survey, carried out in 1996/1997. A multistage random sample (n
      = 4711) of the Estonian population aged 15-79 was interviewed; the response rate
      was 78.3%. This study includes those respondents aged 25-79 (n = 4011) with
      analyses being performed separately for men and women. The study revealed that a
      low educational level, Russian nationality, low personal income and for men only,
      rural residence were the most influential factors underlying poor health.
      Education had the biggest independent effect on health ratings: for women with
      less than an upper secondary education the odds of having poor health were almost
      fourfold (OR = 3.88) when compared to those with a university education, and for
      men these odds were almost two and a half times (OR = 2.32). Material resources,
      in this study measured by personal income, were important factors in explaining
      some of the educational and ethnic differences (especially for Russian women) in
      poor self-rated health. Overall, we found no differences between men and women in
      their health ratings. On the contrary, when we controlled for physical health
      status, emotional distress and locus of control women reported better health than
      men. Health selection contributed to, but did not explain the differences by
      structural dimension. This study also showed a strong association of poor self
      rated health with three correlates-physical health status, emotional distress and
      locus of control, although the influence of these correlates on poor health
      ratings was not seen equally in the different structural dimensions.

PMID- 12190276
TI  - Social inequality in educational achievement and psychosocial adjustment
      throughout childhood: magnitude and mechanisms.
AB  - The paper examines the hypothesis that social inequalities in children's
      developmental resources level off during adolescence against an alternative
      hypothesis that they continue to exert their influence throughout all of
      childhood. Using data from the National Child Development Study, the study
      applies two models. Both are premised on the understanding that the social and
      physical environments in which children are raised affects their resources in the
      domains of educational achievement and psychosocial adjustment. A 'class
      inequalities' model seeks to determine the extent of social class inequalities at
      three key stages in children's development: the transition from infant to junior
      schooling at age 7, from primary to secondary education at age 11 and from
      compulsory education to further education or work at age 16. The second model is
      a contextual-systems model which seeks to expand our understanding of the
      pathways from family social class to children's educational achievement and
      psychosocial adjustment through some more proximal determinants of these
      resources: material deprivation, school composition, parental involvement and
      aspirations. Social class inequalities in educational achievement were found to
      be greater than inequalities in psychosocial adjustment. The same developmental
      pattern was observed for both outcomes: inequalities increased from age 7 to age
      11 and then remained at the same level at 16 yr. The contextual-systems models
      showed that when social inequalities are interpreted more broadly than a narrow
      class based definition, they continue to widen in adolescence. In particular,
      family influences, indicated by parental involvement become less important and
      social contexts beyond the family, reflected in material conditions and school
      composition, become more important. At age 16, material deprivation was the
      strongest determinant of psychosocial adjustment while school composition was
      most strongly related to educational achievement. The contextual-systems model
      provides a more complete account of social inequalities in children's educational
      achievement and psychosocial adjustment than simple estimates of social class
      effects.

PMID- 12190278
TI  - Bone mass, bone mineral density and muscle mass in professional golfers.
AB  - The aim of this study was to determine the effects of long-term professional golf
      participation on whole-body and regional bone mass and density. Dual-energy X-ray
      absorptiometry was performed on 15 male professional golfers and 18 sedentary
      individuals, matched for sex, race, age (29+/-1 and 25+/-1 years, respectively),
      body mass (79+/-2 and 74+/-2 kg), height (1.78+/-0.01 and 1.77+/-0.02 m) and
      percent body fat (20+/-2 and 21+/-2%; mean +/- sx). We found that long-term
      professional golf participation is not associated with significant increments in
      regional or whole-body bone mass or density. Neither the lumbar spine nor the
      femoral neck showed any noticeable enhancement of bone mass in professional
      golfers compared with controls from the same population. The only effect of
      professional golf participation on regional body composition was a 9% increase in
      muscle mass in the dominant arm (P < 0.05).

PMID- 12190279
TI  - Comparison of spine motion in elite golfers with and without low back pain.
AB  - Low back pain is a common musculoskeletal disorder affecting golfers, yet little
      is known of the specific mechanisms responsible for this injury. The aim of this
      study was to compare golf swing spinal motion in three movement planes between
      six male professional golfers with low back pain (age 29.2+/-6.4 years; height
      1.79+/-0.04 m; body mass 78.2+/-12.2 kg; mean +/- s) and six without low back
      pain (age 32.7+/-4.8 years; height 1.75+/-0.03 m; body mass 85.8+/-10.9 kg) using
      a lightweight triaxial electrogoniometer. We found that golfers with low back
      pain tended to flex their spines more when addressing the ball and used
      significantly greater left side bending on the backswing. Golfers with low back
      pain also had less trunk rotation(obtained from a neutral posture), which
      resulted in a relative 'supramaximal' rotation of their spines when swinging.
      Pain-free golfers demonstrated over twice as much trunk flexion velocity on the
      downswing, which could relate to increased abdominal muscle activity in this
      group. This study is the first to show distinct differences in the swing
      mechanics between golfers with and without low back pain and provides valuable
      guidance for clinicians and teachers to improve technique to facilitate recovery
      from golf-related low back pain.

PMID- 12190280
TI  - The effects of outcome imagery on golf-putting performance.
AB  - The aim of this study was to determine the effects of positive and negative
      outcome imagery on golf-putting performance. Players of both high and low ability
      performed a golf-putting task in three imagery conditions: (a) a positive outcome
      imagery condition, (b) a negative outcome imagery condition and (c) a no-imagery
      control condition. The task was conducted in a competitive setting, reducing the
      possibility of demand characteristics. We found that negative outcome imagery was
      detrimental to putting performance; however, performance in the positive outcome
      imagery condition was no better than performance in the control condition. There
      was also evidence to suggest that outcome imagery operated through the mechanism
      of confidence, as negative outcome imagery was detrimental to both confidence and
      performance. The results of the present study suggest that golfers should avoid
      visualizing negative images, as this could damage both confidence and
      performance.

PMID- 12190281
TI  - The efficacy of video feedback for learning the golf swing.
AB  - This study was designed to examine the efficacy of video instruction relative to
      that of verbal and self-guided instruction. Before training, 30 golfers were
      assigned at random to one of three groups: video, verbal or self-guided
      instruction. Video instruction was defined as a practice session in which the
      teacher was aided by the use of video. Verbal instruction was defined as
      practising with the teacher providing verbal feedback. Self-guided practice was
      defined as practising without the aid of a teacher. The participants had a pre
      test, four 90 min practice sessions, an immediate post-test and a 2 week delayed
      post-test. During the pre-test and post-tests, all participants were required to
      strike 15 golf balls, with a 7-iron, from an artificial turf mat for distance and
      accuracy. The results showed that all groups were equal on the pre-test. On the
      first post-test, the two instruction groups performed worse than the self-guided
      group. However, on the second post-test, the two instruction groups performed
      better than the self-guided group, with the video group performing best. We
      interpret these results to mean that video analysis is an effective means of
      practice, but that the positive effects may take some time to develop.

PMID- 12190282
TI  - The vibrational mode structure of a golf ball.
AB  - In this paper, we report the discrete frequencies at which golf balls can
      vibrate, the mode patterns of these vibrations and how these modes can be
      excited. There are two broad classes of modes: those that radiate sound waves and
      those that do not. Both silent and acoustic modes are excited by tangential (i.e.
      spin-producing) impact forces; only acoustic modes are excited by radial impact
      forces. Exact analytical results for a homogeneous ball core are compared with
      finite element numerical results for both a core and a model two-piece ball.
      Correspondences are readily established for the important low-frequency modes,
      and the good agreement suggests the validity of these results for real golf
      balls. The results potentially provide the basis for a rapid, simple and non
      destructive method of measuring the effective high-frequency elastic shear
      modulae of balls (and ball cores) as well as a method for 'tuning' the
      performance of balls for specific clubs. Some of these aspects are explored
      further in our companion paper in this issue.

PMID- 12190283
TI  - On the acoustic signature of golf ball impact.
AB  - In this paper, we present results on the measurement and analysis of the sound
      that is produced by the sharp impact loading of a golf ball by a flat massive
      object (e.g. the face of a golf club). We discuss: (a) the motivation for such a
      study; (b) some necessary background information on how golf balls vibrate; (c)
      the techniques used to acquire and analyse the data; and (d) an analysis of the
      sound made by dropping balls on a smooth, massive concrete target surface. These
      results establish a simple method for rapid and non-destructive measurement of
      the effective high-frequency elastic shear moduli of balls and ball cores.

PMID- 12190284
TI  - Development and use of one-dimensional models of a golf ball.
AB  - One-dimensional models of a golf ball are useful in modelling near-normal (90
      degrees) impact. The model described here has two masses connected by a non
      linear spring in parallel with a non-linear damper. The behaviour of this system
      in collision with an infinite rigid mass is compared with the results of tests
      involving real golf balls. Values of the four unknown constants are found by
      fitting the model results, over a range of impact speeds from zero to 50 m x s(
      1), to the coefficient of restitution and duration of contact found in the tests.
      The simplest model (Model 1) was a good fit for duration of contact over the
      whole range of impact speeds, but for the coefficient of restitution only at high
      speed (above 20 m x s(-1)). However, when used with a similar model of a flexible
      faced club, the simple model predicted the coefficient of restitution of the club
      ball combination, determined by direct testing, quite well and as such is a
      useful screening tool. More complicated Models 2 and 3 fitted the rigid target
      coefficients of restitution better at low speed than Model 1. However, Models 2
      and 3 have other disadvantages and are no better than Model 1 for high-speed
      impact with flexible faced clubs.

PMID- 12190285
TI  - High-performance driver design: benefits for all golfers.
AB  - Here I report experimental data to show the variation in impact efficiency
      between a driver and a standard golf ball with both impact speed and impact
      location. The relationship of these data to the driver impact characteristics of
      the golfing population is presented as a key factor in the face design trade-off
      between increased driver performance and driver fatigue life. Based on these
      driver impact characteristics, a design principle is introduced that segments the
      golfing population based on driver loft, to deliver the benefit of increased
      impact efficiency to all golfers and particularly to average golfers. Example
      drivers created using this design principle are then used to generate
      experimental evidence that counters the widely held belief that gains in impact
      efficiency offered by high-performance drivers benefit only those golfers capable
      of generating the highest speed impacts close to the face centre.

PMID- 12190286
TI  - The pathology of inherited breast cancer.
AB  - Familial breast cancer has been recognised for many years. In the 1990s the
      genetic mechanism of inheritance of a proportion of these familial cancers was
      found to be attributable to germline mutation in either of two newly discovered
      genes, namely BRCA1 and BRCA2. Since the discovery of these genes, studies have
      been performed in which the pathological characteristics of familial cancers
      arising in patients with germline BRCA1 and BRCA2 mutation have been examined. A
      distinct pathological phenotype of high-grade, oestrogen receptor-negative breast
      cancer, often with medullary features, has been consistently described for BRCA1
      cancers. A less distinct phenotype has been described for BRCA2 cancers. The
      discovery of genotype-phenotype correlation has significant implications for
      patient management and novel treatment strategies, not only for inherited
      cancers, but for breast cancer in general.

PMID- 12190287
TI  - C-kit mutations in gastrointestinal stromal tumours.
AB  - AIMS: Gastrointestinal stromal tumours (GISTs), once assumed to be of smooth
      muscle origin, generally express CD117 and CD34, similar to the interstitial
      cells of Cajal. Assessment of malignant potential in GISTs is problematic,
      especially on small biopsies. Some recent data indicate that mutations in the
      juxtamembrane domain (exon 11) of the c-kit (CD117) proto-oncogene may be
      associated with a worse prognosis. In this study, the frequency of c-kit exon 11
      mutations has been determined in a series of 18 gut stromal tumours. METHODS:
      Immunophenotype was assessed by immunoperoxidase stains for smooth muscle actin,
      desmin, S100, CD34 and CD117, and each tumour classified as being of low,
      uncertain (intermediate) or high malignant potential based on standard
      histological criteria. DNA from each tumour was extracted from fresh (n = 5) or
      formalin-fixed, paraffin-embedded (n= 13) tissues using the direct lysis method.
      Exon 11 was amplified by PCR and sequencing of both sense and antisense strands
      was performed on two occasions using an ABI 377 sequencer. RESULTS: Mutations in
      exon 11 were detected in three of 14 confirmed GISTs, two being point mutations
      at codon 560 and one a 3-bp deletion resulting in the in-frame deletion of
      glutamine at codon 561. All three tumours were of high or intermediate malignant
      potential histologically. Three other 'high risk' primary GISTs and a metastatic
      GIST deposit were negative for exon 11 mutations. CONCLUSIONS: Data on this
      relatively small cohort of Australian patients indicate that c-kit exon 11
      mutation analysis does not correlate well with histological assessment of
      malignant potential, and cannot be regarded as a reliable objective marker for
      poor prognosis in GISTs.

PMID- 12190288
TI  - Comparative evaluation of PCR-based methods for the assessment of T cell
      clonality in the diagnosis of T cell lymphoma.
AB  - AIMS: The accurate diagnosis of T cell lymphoma often depends on the
      demonstration of a monoclonal T cell population in a lymphoproliferative disorder
      (LPD). The aim of this study was to evaluate four polymerase chain reaction (PCR)
      based methods used to analyse T cell receptor (TCR) gene rearrangements in the
      assessment of T cell clonality. METHODS: DNA was tested from 23 T cell neoplasms,
      seven B cell non-Hodgkin's lymphomas (B-NHL), three Hodgkin's lymphomas (HL), 14
      benign LPD and peripheral blood from a healthy donor. TCRgamma rearrangements
      were assessed by McCarthy's et al. two primer set method, Benhattar's et al.
      linear pre-amplification method, and Chhanabhai's et aL heteroduplex method.
      TCRbeta D-J rearrangements were analysed by Slack's et al. method. RESULTS:
      Monoclonal TCRgamma rearrangements were found in 91% (21 of 23) of T cell
      neoplasms using McCarthy's et al. method; in 83% (19 of 23) using Benhattar's et
      al. or Chhanabhai's et al. methods and monoclonal TCRbeta rearrangements were
      found in 43% (10 of 23) using Slack's et al. method. Monoclonality was
      established in all T cell neoplasms using one or more PCR methods. One follicular
      B-NHL had inappropriate monoclonal TCRbeta rearrangement, while the remaining B
      NHL and all HL samples had no monoclonal TCRgamma or TCRbeta rearrangements. In
      addition to polyclonal products, one reactive lymph node had oligoclonal TCRgamma
      rearrangements and two others generated monoclonal products of uncertain
      significance. McCarthy's et al. TCRgamma method was the most sensitive in
      establishing T cell monoclonality, and in combination with Slack's et al. TCRbeta
      method, monoclonality was demonstrated in 100% of T cell neoplasms (23 of 23).
      CONCLUSIONS: These data indicate that multiple primer set PCR methods should
      obviate a need for the more expensive and time-consuming Southern blot (SB)
      technique and are the preferred diagnostic molecular test for assessing T cell
      clonality.

PMID- 12190289
TI  - P53 immunohistochemical expression: messages in cervical carcinogenesis.
AB  - AIMS: The pattern of p53 expression was studied in pre-invasive and invasive
      cervical carcinoma in an attempt to clarify its role in cervical carcinogenesis.
      METHODS: A total of 234 invasive cervical carcinomas (152 squamous cell
      carcinomas, 61 adenocarcinomas and 21 adenosquamous carcinomas) and 16 cervical
      intraepithelial neoplasia (CIN) I, six CIN II and 25 CIN III were
      immunohistochemically studied for p53. RESULTS: p53 was detected more frequently
      in CIN and invasive carcinoma (100% of CIN I, 74.2% CIN II + III and 70.1%
      invasive carcinoma) compared with benign cervices (P< 0.001); however, only three
      squamous cell carcinomas, 11 adenocarcinomas and two adenosquamous carcinomas
      exhibited p53 expression in >75% of tumour nuclei. Six of the 11 adenocarcinomas
      and both adenosquamous carcinomas were poorly differentiated compared with one of
      the three squamous carcinomas. p53 immunoreactive cells were randomly distributed
      in invasive carcinoma, confined to the lower third of the epithelium in CIN I,
      reached the middle third in 20% of CIN II and upper third in 16.6% of CIN III.
      CONCLUSIONS: Assuming that p53 immunoreactivity indicates gene mutation when the
      majority (> 75%) of neoplastic cells express p53, p53 mutations would seem
      uncommon in cervical carcinogenesis. Nonetheless, glandular malignancies, in
      particular poorly differentiated variants, may show a higher frequency of
      mutation. p53 was detected more frequently in CIN I compared with CIN II/III and
      invasive carcinoma which may be due to p53 protein degradation following
      interaction with high risk human papillomavirus E6 protein in CIN II/III and
      invasive carcinoma.

PMID- 12190290
TI  - Malakoplakia in association with colorectal carcinoma: a series of four cases.
AB  - AIMS: Malakoplakia is a characteristic inflammatory condition which is usually
      seen in the urogenital tract. Gastrointestinal malakoplakia is seen in
      association with a variety of conditions such as ulcerative colitis, diverticular
      disease, adenomatous polyps and carcinoma. The purpose of this paper is to report
      four additional cases of colorectal cancer associated with malakoplakia and
      review the literature on this association. METHODS: All specimens were
      colectomies for cancer. Routine handling of the specimen with lymph node
      harvesting was performed. In addition to H&E stains, PAS, Perls' Prussian Blue
      and von Kossa stains were performed. RESULTS: Three of the cases were encountered
      in males and the patients ranged in age from 55 to 64 years. One case each
      occurred in the caecum/ascending colon and descending colon, while the remaining
      two were located in the rectum. All four cases were Dukes' stage B tumours.
      Furthermore, all four cases had spread to pericolic fat and two had perforated.
      Microscopic examination showed the malakoplakia to be present at the infiltrating
      edge of the tumours. The draining lymph nodes were involved by malakoplakia to
      varying degrees in all cases. CONCLUSIONS: From this series and the literature
      review, malakoplakia associated with colorectal cancer tends to occur in elderly
      males in the rectum. The malakoplakia is found at the infiltrating front of the
      tumour and is not admixed with the neoplastic glands. Although lymph node
      involvement by malakoplakia has been reported only once previously, all four
      cases in this series showed evidence of involvement. The association does not
      appear to have any prognostic significance.

PMID- 12190291
TI  - Tumoural calcium pyrophosphate dihydrate crystal deposition disease presenting
      clinically as a malignant soft tissue mass diagnosed on fine needle aspiration
      biopsy.
AB  - Tumoural calcium pyrophosphate dihydrate crystal deposition is a rare
      manifestation of calcium pyrophosphate deposition disease (CPPD). We present the
      case of a 75-year-old male with a previously resected rectal adenocarcinoma who
      developed a 5-cm right-sided mass at the base of his neck. Clinically and
      radiologically the lesion was suspicious for malignancy, possibly of metastatic
      origin. A bedside fine needle aspirate was performed and the smears were mildly
      cellular showing histiocytes with numerous intracellular and extracellular
      crystals. These colourless crystals were mostly short and rhomboid shaped and
      demonstrated weakly positive birefringence. A diagnosis of tumoural CPPD was
      made. This case is only the second in the English literature diagnosed on fine
      needle aspiration biopsy. Tumoural CPPD is well known to be a clinical,
      radiological and occasionally pathological mimic of malignancy. Several cases
      have been reported where unnecessary radical surgery was performed for this
      condition. Fine needle aspiration biopsy, as in this case, can provide a rapid
      and accurate diagnosis of CPPD, avoiding the need for invasive procedures.
      Polarisation microscopy is a vital adjunct to confirm this diagnosis.

PMID- 12190292
TI  - Glomus coccygeum may mimic glomus tumour.
AB  - We reviewed all cases of pilonidal sinus excision specimens from our surgical
      pathology records from 1990 to 2000 to determine the presence of glomus
      coccygeum. We found only two cases of glomus coccygeum, also known as coccygeal
      body. We describe the histology and immunohistochemical findings of two glomera
      coccygea incidentally discovered in pilonidal sinus excision specimens, and
      review the world's English literature.

PMID- 12190293
TI  - Effect of long-term mobile communication microwave exposure on vascular
      permeability in mouse brain.
AB  - AIMS: To study the effect of long-term exposure to global system for mobile
      communication (GSM) radiofrequency fields on vascular permeability in murine
      brains. METHODS: Using a purpose-designed exposure system at 900 MHz, mice were
      given a 60-minute far-field, whole body exposure on each of 5 days per week for
      104 weeks at specific absorption rates (SAR) of 0.25, 1.0,2.0 and 4.0 W/kg.
      Control mice were sham-exposed or permitted free movement in a cage to evaluate
      any stress-related effects. Albumin immunohistochemistry was used to detect
      increased vascular permeability and the efficacy of the vascular tracer was
      confirmed with a positive control group exposed to a clostridial toxin known to
      increase vascular permeability in the brain. RESULTS: In all exposed and control
      groups, albumin extravasation was minimal, often leptomeningeal, and was deemed
      insignificant as a maximum of three capillaries or venules in a given brain
      showed leakage from the very many blood vessels present in the three coronal
      brain sections. CONCLUSIONS: These results suggest that prolonged exposure to
      mobile telephone-type radiation produces negligible disruption to blood-brain
      barrier integrity at the light microscope level using endogenous albumin as a
      vascular tracer.

PMID- 12190294
TI  - A 9-year retrospective assessment of laboratory testing for activated protein C
      resistance: evolution of a novel approach to thrombophilia investigations.
AB  - AIMS: To assess international and local trends in laboratory testing for
      activated protein C (APC) resistance (APCR) and factor V Leiden (FVL). Also, to
      compare local results of FVL testing with a variety of different clot-based APCR
      assays to assess utility for detection of APCR both related and unrelated to FVL.
      METHODS: Local test statistics and test result patterns were evaluated and
      international literature was reviewed over the past 9 years. Direct comparisons
      of FVL testing by DNA analysis against (a) the standard APTT-based APCR assay,
      with and without pre-dilution with factor V deficient (FVD) plasma, or with and
      without normalisation, and (b) three alternative RVVT-based procedures (most
      recently using a commercial RVVT-based procedure called GradiLeiden V; GLV). In
      total, data obtained over the past 7 years, using referred samples from over
      1,000 patients, have been assessed. RESULTS: The 9-year retrospective assessment
      has seen many changes in test-based processes. Locally, test requests for both
      APCR and FVL have consistently increased. We suspect this has been fuelled in
      part by media reports of 'economy class syndrome' (ECS) and associated general
      public and clinical concern. Current request patterns number around 800 APCR and
      1,600 FVL per year. Interestingly, most requests are for one or either test, with
      joint requests comprising less than 20% of those overall. Although test requests
      are increasing, detection of the FVL defect as a proportion of test requests is
      actually falling (from a high of over 25% in 1996 to around 14% currently).
      Whether this suggests an increasing tendency for clinical ordering in the absence
      of appropriate clinical histories is a matter of concern. Consistent with
      previous findings, the original and commonly used APTT-based procedure was found
      to show the least correlation with DNA findings, with a large overlap between FVL
      and non-FVL individuals. The alternate-RVVT-based procedures showed much better
      differentiation. Thus, for the APTT-based method, in order to ensure 100%
      sensitivity, an APC ratio cut-off value of 3.1 was required, and this yielded
      only 49.1% specificity. In contrast, for the GLV RVVT-based method, in order to
      ensure 100% sensitivity, an APC ratio cut-off value of 1.65 was required, and
      this yielded 96.6% specificity. CONCLUSIONS: It is important to recognise the
      limitation of APTT-based assays to discriminate FVL. However, a combination of
      RVVT- and APTT-based testing is still recommended, as this will provide excellent
      discriminatory power for the FVL defect, particularly negative prediction, in
      addition to detection of potential APCR unrelated to FVL, as well as detection of
      other potential haemostatic disturbances. Accordingly, we detail strategies,
      including a test algorithm that we are currently using to improve our detection
      of APCR and prediction of FVL, and use of clotting-based procedures as the first
      line approach.

PMID- 12190295
TI  - IgM paraproteinaemia: disease associations and laboratory features.
AB  - AIMS: To review the disease associations and laboratory features occurring in IgM
      paraproteinaemia. METHODS: Systematic review of all new serum IgM paraproteins
      detected over a 6-year period in an immunodiagnostic laboratory serving a
      population of 400,000 people. Clinical diagnoses were ascertained from a
      computerised laboratory database or clinical notes, whilst associated laboratory
      features were obtained from the same sources. RESULTS: The 125 IgM paraproteins
      detected constitute 19.7% of all new paraproteins observed over the period of
      study. IgM paraproteinaemia occurred more commonly in males and its frequency
      increased with age. Approximately 30% were associated with B cell
      lymphoproliferative disorders (Waldenstrom's macroglobulinaemia, non-Hodgkin's
      lymphoma, chronic lymphocytic leukaemia, amyloid, etc.) with the remainder being
      labelled as monoclonal IgM gammopathies of uncertain significance (four having a
      peripheral neuropathy). At clinical presentation, patients with
      lymphoproliferative disorders tended to have higher levels of IgM, beta2
      microglobulin, the presence of free urinary light chains and demonstrated
      molecular size heterogenicity of the paraprotein (presence of decamers, oligomers
      and monomers in addition to the pentamer) but there was considerable overlap. A
      good correlation was noted between paraprotein concentration and viscosity in
      most patients. CONCLUSION: IgM paraproteinaemia was most frequently encountered
      in the context of a gammopathy of uncertain significance. Features which
      suggested lymphoproliferative disorders included higher levels of paraprotein
      (>15 g/l) elevated levels of beta2-microglobulin and the presence of urinary free
      high chain. However, as much overlap was seen, regular monitoring of paraprotein
      levels is considered mandatory in the management of these patients.

PMID- 12190297
TI  - Statistics in the pathology laboratory: diagnostic test interpretation.
AB  - Appropriate interpretation of diagnostic tests is critical in clinical practice.
      Reference ranges are used most commonly but these can be misleading. The
      calculation of post-test probability of disease is a useful alternative as it
      provides an estimate of disease likelihood given a particular test result. The
      assessment of post-test probability and problems associated with reference ranges
      are discussed in this review.

PMID- 12190296
TI  - Detection of extended spectrum beta-lactamases in the routine clinical
      microbiology laboratory.
AB  - AIMS: To compare three methods of confirming the presence of an extended spectrum
      beta-lactamase (ESBL) enzyme with the initial detection (i.e., screening) by the
      Vitek AMS. METHODS: Gram-negative bacteria which flagged as ESBL-positive in the
      Vitek GNS card, or were suspected of harbouring an enzyme, were further tested by
      each of the following methods: (a) combination disc test using cefpodoxime,
      ceftazidime and cefotaxime with and without clavulanate; (b) cefotaxime ESBL
      Etest; and (c) Jarlier keyhole method with cefpodoxime (10 microg), cefotaxime (5
      microg) and aztreonam (30 microg) placed 15mm away from an augmentin (30 microg)
      disc. RESULTS: A total of 52 isolates were investigated, representing an 18-month
      time period. Fifty of these were positive by Vitek. Twenty-eight (56%) were
      confirmed by other methods (true positives). Of the 44% Vitek
      positive/confirmatory test-negative (false positives), eight were Escherichia
      coli which was 53% of all E. coli tested. The majority of other false-positive
      isolates were Klebsiella oxytoca (24% overall) which were all Vitek- and Etest
      positive but negative by the combination disc test. CONCLUSIONS: All ESBL
      positive strains by Vitek should be confirmed by the combination disc test using
      all three antibiotics. This will enable differentiation of 'true' ESBLs from
      false-positive organisms, including K1 hyperbetalactamase-producing Klebsiella
      oxytoca and AmpC-producing organisms. The cefpodoxime combination discs gave the
      best differentiation in this study with only one ESBL organism being missed.

PMID- 12190298
TI  - An unusual pleural spindle cell tumour. Part 1.

PMID- 12190299
TI  - Placental mesenchymal dysplasia.

PMID- 12190300
TI  - Eccrine angiomatous hamartoma in a neurofibromatosis type-1 patient.

PMID- 12190301
TI  - Vascular and valvular involvement by neurofibromatosis.

PMID- 12190302
TI  - Arylsulfonamidothiazoles as a new class of potential antidiabetic drugs.
      Discovery of potent and selective inhibitors of the 11beta-hydroxysteroid
      dehydrogenase type 1.
AB  - Novel antidiabetic arylsulfonamidothiazoles are presented that exert action
      through selective inhibition of the 11beta-hydroxysteroid dehydrogenase type 1
      (11beta-HSD1) enzyme, thereby attenuating hepatic gluconeogenesis. The
      diethylamide derivative 2a was shown to potently inhibit human 11beta-HSD1
      (IC(50) = 52 nM), whereas the N-methylpiperazinamide analogue 2b only inhibited
      murine 11beta-HSD1 (IC(50) = 96 nM). Both compounds showed >200-fold selectivity
      over human and murine 11beta-HSD2. 2b was subsequently shown to reduce glucose
      levels in diabetic KKA(y) mice, substantiating the 11beta-HSD1 enzyme as a target
      for the treatment of type 2 diabetes.

PMID- 12190303
TI  - SAR by MS: a ligand based technique for drug lead discovery against structured
      RNA targets.
AB  - A technique for lead discovery vs RNA targets utilizing mass spectrometry (MS)
      screening methods is described. The structure-activity relationships (SAR)
      derived from assaying weak binding motifs allows the pharmacophores discovered to
      be elaborated via "SAR by MS" to higher affinity ligands. Application of this
      strategy to a subdomain of the 23S rRNA afforded a new class of compounds with
      functional activity.

PMID- 12190304
TI  - Solid phase synthesis and evaluation of Tyr-Tic-Phe-Phe(p-NHCOCH(2)Br) ([Phe(p
      bromoacetamide)(4)]TIPP), a potent affinity label for delta opioid receptors.
AB  - Derivatives of the delta opioid receptor selective peptide Tyr-Tic-Phe-Phe-OH
      (TIPP) containing a p-bromoacetamide moiety on the phenyl ring of Phe(3) or
      Phe(4) were prepared by solid phase synthesis. [Phe(p-NHCOCH(2)Br)(4)]TIPP
      exhibited high affinity for cloned delta receptors (IC(50) = 5.4 nM), and
      incubation with only 2.5 nM resulted in 85% wash resistant inhibition of
      radioligand binding to delta receptors. Therefore, this peptide is a potent
      affinity label for further study of delta opioid receptors.

PMID- 12190305
TI  - Orally active, water-soluble antimalarial 3-aryltrioxanes: short synthesis and
      preclinical efficacy testing in rodents.
AB  - Short chemical syntheses of four new antimalarial trioxanes are presented,
      starting with inexpensive and commercially available cyclohexanone. Almost
      exclusive formation of the trioxane 12alpha-stereoisomers simplifies product
      purification. Carboxyphenyltrioxanes 3 and 5 are thermally stable in air even at
      60 degrees C for 24 h. When administered orally, these new carboxyphenyltrioxanes
      are highly efficacious in curing malaria-infected mice. Important for their
      practical in vivo administration, these new synthetic antimalarial trioxanes 3
      and 5 are 14-20 times more soluble in water at pH 7.4 than is artelinic acid (1),
      a leading semisynthetic, herb-derived antimalarial trioxane drug candidate.

PMID- 12190306
TI  - Discovery of N-isoxazolyl biphenylsulfonamides as potent dual angiotensin II and
      endothelin A receptor antagonists.
AB  - The ET(A) receptor antagonist (2) (N-(3,4-dimethyl-5-isoxazolyl)-4'-(2-oxazolyl)
      [1,1'-biphenyl]-2-sulfonamide, BMS-193884) shares the same biphenyl core as a
      large number of AT(1) receptor antagonists, including irbesartan (3). Thus, it
      was hypothesized that merging the structural elements of 2 with those of the
      biphenyl AT(1) antagonists (e.g., irbesartan) would yield a compound with dual
      activity for both receptors. This strategy led to the design, synthesis, and
      discovery of (15) (4'-[(2-butyl-4-oxo-1,3-diazaspiro[4.4]non-1-en-3-yl)methyl]-N
      (3,4-dimethyl-5-isoxazolyl)-2'-[(3,3-dimethyl-2-oxo-1-pyrrolidinyl)methyl]-[1,1'
      biphenyl]-2-sulfonamide, BMS-248360) as a potent and orally active dual
      antagonist of both AT(1) and ET(A) receptors. Compound 15 represents a new
      approach to treating hypertension.

PMID- 12190307
TI  - Structural basis for understanding structure-activity relationships for the
      glutamate binding site of the NMDA receptor.
AB  - We present new homology-based models of the glutamate binding site (in closed and
      open forms) of the NMDA receptor NR2B subunit derived from X-ray structures of
      the water soluble AMPA sensitive glutamate receptor. The models were used for
      revealing binding modes of agonists and competitive antagonists, as well as for
      rationalizing known experimental facts concerning structure-activity
      relationships: (i) the switching between the agonist and the antagonist modes of
      action upon lengthening the chain between the distal acidic group and the amino
      acid moiety, (ii) the preference for the methyl group attached to the alpha-amino
      group of ligands, (iii) the preference for the D-configuration of agonists and
      antagonists, and (iv) the existence of "superacidic" agonists.

PMID- 12190308
TI  - Toward a pharmacophore for drugs inducing the long QT syndrome: insights from a
      CoMFA study of HERG K(+) channel blockers.
AB  - In this paper, we present a pharmacophore for QT-prolonging drugs, along with a
      3D QSAR (CoMFA) study for a series of very structurally variegate HERG K(+)
      channel blockers. The blockade of HERG K(+) channels is one of the most important
      molecular mechanisms through which QT-prolonging drugs increase cardiac action
      potential duration. Since QT prolongation is one of the most undesirable side
      effects of drugs, we first tried to identify the minimum set of molecular
      features responsible for this action and then we attempted to develop a
      quantitative model correlating the 3D stereoelectronic characteristics of the
      molecules with their HERG blocking potency. Having considered an initial set of
      31 QT-prolonging drugs for which the HERG K(+) channel blocking activity was
      measured on mammalian transfected cells, we started the construction of a
      theoretical screening tool able to predict whether a new molecule can interact
      with the HERG channel and eventually induce the long QT syndrome. This in silico
      tool might be useful in the design of new drug candidates devoid of the
      physicochemical features likely to cause the above-mentioned side effect.

PMID- 12190309
TI  - Exploring the role of bromine at C(10) of (+)-4-[2-[4-(8-chloro-3,10-dibromo-
      6,11-dihydro-5H-benzo[5,6]cyclohepta[1,2-b]pyridin-11(R)-yl)-1-piperidinyl]-2-
      oxoethyl]-1-piperidinecarboxamide (Sch-66336): the discovery of
      indolocycloheptapyridine inhibitors of farnesyl protein transferase.
AB  - The 10-bromobenzocycloheptapyridyl farnesyl transferase inhibitor (FTI) Sch-66336
      (1) is currently under clinical evaluation for the treatment of human cancers.
      During structure-activity relationship development leading to 1, 10
      bromobenzocycloheptapyridyl FTIs were found to be more potent than analogous
      compounds lacking the 10-Br substituent. This potency enhancement was believed to
      be due, in part, to an increase in conformational rigidity as the 10-bromo
      substituent could restrict the conformation of the appended C(11) piperidyl
      substituent in an axial orientation. A novel and potent class of FTIs,
      represented by indolocycloheptapyridine Sch-207758 [(+)-10a], have been designed
      based on this principle. Although structural and thermodynamic results suggest
      that entropy plays a crucial role in the increased potency observed with (+)-10a
      through conformational constraints and solvation effects, the results also
      indicate that the indolocycloheptapyridine moiety in (+)-10a provides increased
      hydrophobic interactions with the protein through the addition of the indole
      group. This report details the X-ray structure and the thermodynamic and
      pharmacokinetic profiles of (+)-10a, as well as the synthesis of
      indolocycloheptapyridine FTIs and their potencies in biochemical and biological
      assays.

PMID- 12190310
TI  - Anilinoquinazoline inhibitors of fructose 1,6-bisphosphatase bind at a novel
      allosteric site: synthesis, in vitro characterization, and X-ray crystallography.
AB  - The synthesis and in vitro structure-activity relationships (SAR) of a novel
      series of anilinoquinazolines as allosteric inhibitors of fructose-1,6
      bisphosphatase (F16Bpase) are reported. The compounds have a different SAR as
      inhibitors of F16Bpase than anilinoquinazolines previously reported. Selective
      inhibition of F16Bpase can be attained through the addition of appropriate polar
      functional groups at the quinazoline 2-position, thus separating the F16Bpase
      inhibitory activity from the epidermal growth factor receptor tyrosine kinase
      inhibitory activity previously observed with similar structures. The compounds
      have been found to bind at a symmetry-repeated novel allosteric site at the
      subunit interface of the enzyme. Inhibition is brought about by binding to a loop
      comprised of residues 52-72, preventing the necessary participation of these
      residues in the assembly of the catalytic site. Mutagenesis studies have
      identified the key amino acid residues in the loop that are required for
      inhibitor recognition and binding.

PMID- 12190311
TI  - Discovery of further pyrrolidine trans-lactams as inhibitors of human neutrophil
      elastase (HNE) with potential as development candidates and the crystal structure
      of HNE complexed with an inhibitor (GW475151).
AB  - Described herein is a modern approach to the rapid preparation and evaluation of
      compounds as potential back-up drug candidates. GW311616A, 1, a derivative of
      pyrrolidine trans-lactams, has previously been described as a potent, orally
      active inhibitor of human neutrophil elastase (HNE) for the treatment of
      respiratory disease. These properties made it a suitable candidate for
      development. Described here is the discovery of three further derivatives of
      pyrrolidine trans-lactams, which fulfill the criteria required for back-up
      candidates 28, 29, and 32. These include increased activity in inhibiting HNE in
      human whole blood (HWB) and comparable pharmacokinetic properties, in particular
      clearance, in two species. To provide a rapid assessment of clearance, cassette
      dosing in dog was used. Modern array techniques, including the synthesis of
      mixtures, were used to synthesize compounds rapidly. Having selected three
      potential compounds as back-up candidates, they were prepared as single
      enantiomers and profiled in in vitro and in vivo assays and evaluated
      pharmacokinetically in rat and dog. These compounds are highly potent and
      selective HNE inhibitors, with a prolonged pharmacodynamic action.
      Pharmacokinetically, these compounds are comparable with 1 while they are more
      potent in HWB. Compound 28, however, has a higher clearance. One of these
      compounds, 32, was cocrystallized with HNE, and features of this structure are
      described and compared with the cocrystal structure of 1 in porcine pancreatic
      elastase.

PMID- 12190312
TI  - Chiral N,N-disubstituted trifluoro-3-amino-2-propanols are potent inhibitors of
      cholesteryl ester transfer protein.
AB  - A novel series of substituted N-benzyl-N-phenyl-trifluoro-3-amino-2-propanols are
      described that reversibly inhibit cholesteryl ester transfer protein (CETP).
      Starting with screening lead 22, various structural features were explored with
      respect to inhibition of the CETP-mediated transfer of [(3)H]cholesterol from
      high-density cholesterol donor particles to low-density cholesterol acceptor
      particles. The free hydroxyl group of the propanol was required for high potency,
      since acylation or alkylation reduced activity. High inhibitory potency was also
      associated with 3-ether moieties in the aniline ring, and the highest potencies
      were exhibited by 3-phenoxyaniline analogues. Activity was substantially reduced
      by oxidation or substitution in the methylene of the benzylic group, implying
      that the benzyl ring orientation was important for activity. In the benzylic
      group, substitution at the 3-position was preferred over either the 2- or the 4
      positions. Highest potencies were observed with inhibitors in which the 3
      benzylic substituent had the potential to adopt an out of plane orientation with
      respect to the phenyl ring. The best 3-benzylic substituents were OCF(2)CF(2)H
      (42, IC(50) 0.14 microM in buffer, 5.6 microM in human serum), cyclopentyl (39),
      3-iso-propoxy (27), SCF(3) (67), and C(CF(3))(2)OH (36). Separation of 42 into
      its enantiomers unexpectedly showed that the minor R(+) enantiomer 1a was 40-fold
      more potent (IC(50) 0.02 microM in buffer, 0.6 microM in human serum) than the
      major S(-) enantiomer 1b, demonstrating that the R-chirality at the propanol 2
      position is key to high potency in this series. The R(+) enantiomer 1a represents
      the first reported acyclic CETP inhibitor with submicromolar potency in plasma. A
      chiral synthesis of 1a is reported.

PMID- 12190313
TI  - Discovery of aminothiazole inhibitors of cyclin-dependent kinase 2: synthesis, X
      ray crystallographic analysis, and biological activities.
AB  - High throughput screening identified 2-acetamido-thiazolylthio acetic ester 1 as
      an inhibitor of cyclin-dependent kinase 2 (CDK2). Because this compound is
      inactive in cells and unstable in plasma, we have stabilized it to metabolic
      hydrolysis by replacing the ester moiety with a 5-ethyl-substituted oxazole as in
      compound 14. Combinatorial and parallel synthesis provided a rapid analysis of
      the structure-activity relationship (SAR) for these inhibitors of CDK2, and over
      100 analogues with IC(50) values in the 1-10 nM range were rapidly prepared. The
      X-ray crystallographic data of the inhibitors bound to the active site of CDK2
      protein provided insight into the binding modes of these inhibitors, and the SAR
      of this series of analogues was rationalized. Many of these analogues displayed
      potent and broad spectrum antiproliferative activity across a panel of tumor cell
      lines in vitro. In addition, A2780 ovarian carcinoma cells undergo rapid
      apoptosis following exposure to CDK2 inhibitors of this class. Mechanism of
      action studies have confirmed that the phosphorylation of CDK2 substrates such as
      RB, histone H1, and DNA polymerase alpha (p70 subunit) is reduced in the presence
      of compound 14. Further optimization led to compounds such as water soluble 45,
      which possesses a favorable pharmacokinetic profile in mice and demonstrates
      significant antitumor activity in vivo in several murine and human models,
      including an engineered murine mammary tumor that overexpresses cyclin E, the
      coactivator of CDK2.

PMID- 12190314
TI  - Synthesis and evaluation of Glypsi(PO(2)R-N)Pro-containing pseudopeptides as
      novel inhibitors of the human cyclophilin hCyp-18.
AB  - The human cyclophilin hCyp-18, an abundant peptidyl-prolyl cis-trans isomerase
      (PPIase) implicated in protein folding, controls the infection of CD4(+) T-cells
      by HIV-1, the pathologic agent of AIDS. Therefore, hCyp-18 is an interesting
      target for the development of novel anti-HIV-1 therapeutics. We focused on the
      design of transition-state analogue inhibitors of the PPIase activity of
      cyclophilin. Most experimental results reported in the literature suggest that
      hCyp-18 catalyzes the pyramidalization of the nitrogen of pyrrolidine via an H
      bond network which results in the deconjugation of the amino acyl-prolyl peptide
      bond. We proposed the Glypsi(PO(2)R(1)-N)Pro motif (R = alkyl or H) as a
      selective transition-state analogue inhibitor of cyclophilin. This motif was
      inserted in Suc-Ala-Ala-Pro-Phe-pNA, a peptide substrate of hCyp-18. The
      pseudopeptide Suc-Ala-Glypsi(PO(2)Et-N)Pro-Phe-pNA 1b bound to hCyp-18 (K(d) = 20
      +/- 5 microM) and was able to selectively inhibit its PPIase activity (IC(50) =
      15 +/- 1 microM) but not hFKBP-12, another important PPIase. Deprotection of the
      phosphonamidate moiety resulted in a complete lack of inhibition. We previously
      demonstrated that reduction of the Phe-pNA moiety caused a quantitative reduction
      of the affinity; however, Suc-Ala-Glypsi(PO(2)Et-N)Pro-Phepsi(CH(2)-NH)pNA 7b
      still bound and inhibited hCyp-18, suggesting that the Glypsi(PO(2)Et-N)Pro motif
      plays the major role in the binding to cyclophilin. Consequently, we propose
      compound 1b as being a novel transition-state mimic inhibitor of hCyp-18.

PMID- 12190316
TI  - Divalent and trivalent alpha-ketocarboxylic acids as inhibitors of protein
      tyrosine phosphatases.
AB  - Protein tyrosine phosphatases (PTPases) are important targets for the treatment
      of insulin resistance in patients with type II diabetes and as antibacterial
      agents. As a result, there is a growing interest in the development of potent and
      specific inhibitors for these enzymes. This paper describes a series of
      inhibitors that contain two or three alpha-ketocarboxylic acid groups that are
      designed to form multiple contacts with residues inside or near the active site
      of phosphatases. The inhibitors have been assayed against three PTPases: the
      Yersinia PTPase, PTP1B, and LAR. The best of the inhibitors has IC(50) values
      against the Yersinia PTPase and PTP1B of 0.7 and 2.7 microM, respectively. These
      divalent and trivalent compounds are significantly more potent than their
      corresponding monovalent analogues. In addition, they show good selectivity for
      PTP1B and the Yersinia PTPase as compared to LAR.

PMID- 12190315
TI  - Synthesis of 3' '-substituted TSAO derivatives with anti-HIV-1 and anti-HIV-2
      activity through an efficient palladium-catalyzed cross-coupling approach.
AB  - Various synthetic studies for the introduction of several functional groups at
      position 3' ' of the spiro moiety of TSAO derivatives have been explored. Among
      them, Stille cross-coupling of 3' '-iodo-TSAO derivatives with different
      stannanes provided an efficient and straightforward route for the direct and
      selective functionalization of the 3' '-position of the sultone spiro moiety via
      carbon-carbon bond formation. The compounds synthesized were evaluated for their
      inhibitory effect on HIV-1 and HIV-2 replication in cell culture. The
      introduction of a bromine and particularly an iodine at the 3' '-position
      conferred the highest anti-HIV-1 activity. In contrast, the presence at this
      position of (un)substituted vinyl, alkynyl, phenyl, or thienyl groups markedly
      diminished the anti-HIV-1 activity. Surprisingly, several of the 3' '-alkenyl
      substituted TSAO derivatives also gained anti-HIV-2 activity at subtoxic
      concentrations, an observation that is very unusual for NNRTIs and never observed
      before for TSAO derivatives. Finally, the anti-HIV-1 activity of some of the 3' '
      substituted TSAO derivatives is discussed in light of our recently proposed
      molecular model of interaction of TSAO derivatives with the interphase between
      the two subunits of HIV-1 reverse transcriptase.

PMID- 12190317
TI  - Synthesis of conformationally constrained analogues of linezolid: structure
      activity relationship (SAR) studies on selected novel tricyclic oxazolidinones.
AB  - In an effort to discover potent antibacterials based on the entropically favored
      "bioactive conformation" approach, we have designed and synthesized a series of
      novel tricyclic molecules mimicking the conformationally constrained structure of
      the oxazolidinone antibacterial, Linezolid 1. The structure 3 obtained by this
      approach was synthesized and found to be moderately active against a panel of
      Gram-positive organisms tested. Further introduction of a fluorine atom in the
      aromatic ring of compound 3 as in Linezolid resulted in some excellent compounds
      possessing potent antibacterial activity. The thus obtained lead molecule 16 was
      further fine-tuned by structure-activity relationship studies on the amide
      functionality leading to a number of novel tricyclic oxazolidinone derivatives.
      Some particularly interesting compounds include the thioamides 36 and 37,
      thiocarbamate 41, and thiourea 45. The in vitro activity results of amide
      homologues of 16 (compounds 25-30) revealed that compounds up to four carbon
      atoms on the amide nitrogen retain the activity. In general, thioamides and
      thiocarbamates are more potent when compared to the corresponding amides and
      carbamates.

PMID- 12190318
TI  - Synthesis and initial evaluation for in vivo chelation of Pu(IV) of a mixed
      octadentate spermine-based ligand containing 4-carbamoyl-3-hydroxy-1-methyl-2(1H)
      pyridinone and 6-carbamoyl-1-hydroxy-2(1H)-pyridinone.
AB  - An improved synthesis for a series of 1-hydroxy-2(1H)-pyridinone-based
      octadentate ligands is reported. The mixed chelate, octadentate ligand, 3,4,3
      LI(1,2-Me-3,2-HOPO), was designed, synthesized, and tested for in vivo chelation
      of Pu in a mouse model. This ligand incorporates both 1,2-HOPO and Me-3,2-HOPO
      metal chelating units; the latter has higher affinity toward actinide ions than
      does 1,2-HOPO at physiological pH. Injected or administered orally to fasted or
      normally fed mice at the standard clinical dose 30 micromol/kg, both 3,4,3-LI(1,2
      HOPO) and 3,4,3-LI(1,2-Me-3,2-HOPO) remove significantly more Pu than injected
      CaNa(3)DTPA. Injected doses of 0.1 micromol/kg of these HOPO ligands are as
      effective as 30 micromol/kg of injected CaNa(3)DTPA. Ten daily injections of 30
      micromol/kg of a HOPO ligand did not induce detectable acute toxicity in mice.
      The mixed HOPO ligand is somewhat more effective than 3,4,3-LI(1,2-HOPO) when
      given orally, and the enhanced reduction of liver Pu by the mixed ligand is
      statistically significant. Thus, both octadentate HOPO ligands meet the criterion
      of low toxicity at doses that are more effective than the standard dose of
      CaNa(3)DTPA. Their improved effectiveness at low dose along with great oral
      activity (despite low gastrointestinal absorption) implies that new treatment
      regimens can be developed using the HOPO ligands alone or as adjuncts to
      CaNa(3)DTPA therapy, which will greatly exceed the amount of Pu excretion that is
      achievable with CaNa(3)DTPA alone.

PMID- 12190320
TI  - Design, synthesis, and biological evaluation of aryloxyethyl thiocyanate
      derivatives against Trypanosoma cruzi.
AB  - As a continuation of our project aimed at the search for new and safe
      chemotherapeutic and chemoprophylactic agents against American trypanosomiasis
      (Chagas' disease), several drugs structurally related to 4-phenoxyphenoxyethyl
      thiocyanate (4) were designed, synthesized, and evaluated as antiproliferative
      agents against the parasite responsible for this disease, the hemoflagellated
      protozoan Trypanosoma cruzi. This thiocyanate derivative was previously shown to
      be an effective and potent agent against T. cruzi proliferation. Several drugs
      possessing thiocyanate groups proved to be effective growth inhibitors of T.
      cruzi growth. Among the designed compounds, it is important to point out the
      extremely potent activity shown by 11, 23, 38, 53, 90, 99, and 117 against the
      epimastigote forms of the parasite. All of them exhibited IC(50) values in the
      low micromolar range, and these values were comparable with those presented by
      our lead drug 4 and ketokonazole, a well-known antiparasitic agent. The activity
      displayed by the nitrogen-containing derivative 90 was very promising with IC(50)
      values of 3.3 microM. Several other thiocyanate derivatives also proved to be
      very potent inhibitors of the multiplication of T. cruzi epimastigotes, such as
      compounds 28, 33, 43, 48, 56, 61, 66, 71, 76, and 124. Compound 43 resulted in
      being a promising drug because it was also very effective against amastigotes,
      the clinically more relevant form of the parasite. This compound was 3-fold more
      potent than 4, while 11 showed nearly the same activity as our lead drug against
      intracellular T. cruzi. It was very surprising that the experimental juvenoid
      124, although fairly devoid of activity against epimastigotes, was very effective
      against intracellular amastigotes growing in myoblasts. The rest of the designed
      compounds showed a broad degree of inhibitory action, from moderately active
      drugs to drugs almost devoid of antiparasitic activity. Compound 43 is an
      interesting example of an effective antichagasic agent that presents excellent
      prospectives not only as a lead drug but also to be used for further in vivo
      studies.

PMID- 12190319
TI  - Design, synthesis, and SAR of tachykinin antagonists: modulation of balance in
      NK(1)/NK(2) receptor antagonist activity.
AB  - Through optimization of compounds based on the dual NK(1)/NK(2) antagonist
      ZD6021, it was found that alteration of two key regions could modulate the
      balance of NK(1) and NK(2) potency. Substitution of the 2-naphthalene position in
      analogues of ZD6021 resulted in increased NK(1) potency and thus afforded NK(1)
      preferential antagonists. Alterations of the piperidine region could then
      increase NK(2) potency to restore dual NK(1)/NK(2) selectivity. Through these
      efforts, three novel receptor antagonists from a single chemically related series
      were identified; two are dual NK(1)/NK(2) antagonists, and the third is an NK(1)
      preferential antagonist. In this paper, the factors affecting the balance of
      NK(1) and NK(2) selectivity in this series are discussed and the in vitro and in
      vivo properties of the novel antagonists are described.

PMID- 12190321
TI  - Influence of bulky substituents on histamine h(3) receptor agonist/antagonist
      properties.
AB  - Novel derivatives of 3-(1H-imidazol-4-yl)propanol were designed on the basis of
      lead compounds belonging to the carbamate or ether series possessing (partial)
      agonist properties on screening assays of the histamine H(3) receptor. One pair
      of enantiomers in the series of alpha-methyl-branched chiral carbamates was
      stereoselectively prepared in high optical yields. Enantiomeric purity was
      checked by Mosher amide derivatives of precursors and capillary electrophoresis
      of the final compounds with trimethyl-beta-cyclodextrin as chiral selector, and
      was determined to be >/=95%. The novel compounds were investigated in various
      histamine H(3) receptor assays in vitro and in vivo. Some compounds displayed
      partial agonist activity on synaptosomes of rat brain cortex, whereas others
      exhibited antagonist properties only. Selected compounds were investigated in
      [(125)I]iodoproxyfan binding studies on the human histamine H(3) receptor and
      showed high affinity in the nanomolar concentration range. Under in vivo
      conditions after oral administration to mice, some of the compounds exhibited
      partial or full agonist activity in the brain at low dosages. The (S)-enantiomer
      of one pair of chiral carbamates (9) proved to be the eutomer; thus, the (S)
      enantiomer was selected for further pharmacological studies. In a peripheral in
      vivo test model in rats, measuring the level of inhibition of capsaicin-induced
      plasma extravasation, (S)-9 again proved its high oral agonist potency with full
      intrinsic activity (ED(50) values of 0.07-0.1 mg/kg depending on tissue).

PMID- 12190322
TI  - 6-Chloropyridazin-3-yl derivatives active as nicotinic agents: synthesis,
      binding, and modeling studies.
AB  - 3,8-Diazabicyclo[3.2.1]octane (1), 2,5-diazabicyclo[2.2.1]heptane (2), piperazine
      (3), and homopiperazine (4) derivatives, substituted at one nitrogen atom with
      the 6-chloro-3-pyridazinyl group while the other nitrogen atom was either
      unsubstituted or mono- or dimethylated, were synthesized and tested for their
      affinity toward the neuronal nicotinic acetylcholine receptors (nAChRs). All of
      the compounds had K(i) values in the nanomolar range. A molecular modeling study
      allowed location of their preferred conformations, the energies of which were
      recalculated in water with a continuum solvent model. Some of the compounds
      showed, in their populated conformations, only pharmacophoric distances longer
      than the values taken into consideration by the Sheridan model for nAChRs
      receptors. Thus, this SAR study gives support to the hypothesis that these longer
      distances are still compatible with affinity for alpha4beta2 receptors in the
      nanomolar range.

PMID- 12190323
TI  - Synthesis of a small library of 3-(carboranylalkyl)thymidines and their
      biological evaluation as substrates for human thymidine kinases 1 and 2.
AB  - A small library consisting of two series of thymidine derivatives containing o
      carboranylalkyl groups at the N-3 position was prepared. In both series, alkyl
      spacers of 2-7 methylene units were placed between the o-carborane cage and the
      thymidine scaffold. In one series, an additional dihydroxypropyl substituent was
      introduced at the second carbon atom of the carborane cage. In the series of N-3
      substituted carboranyl thymidines without additional dihydroxypropyl substituent,
      three steps were required to obtain the target compounds in overall yields as
      high as 75%, while in the series of N-3-substituted carboranyl thymidines with
      additional dihydroxypropyl substituent, 9-10 steps were necessary with
      significantly lower overall yield. All target compounds were good substrates of
      human cytosolic thymidine kinase 1 while they were, if at all, poor substrates of
      the mitochondrial thymidine kinase 2. There was only a minor difference in
      phosphorylation rates between N-3-substituted carboranyl thymidines with
      additional dihydroxypropyl substituents with thymidine kinase 1 (range: 13-49%
      relative to thymidine) and their counterparts lacking this group (range: 11-57%
      relative to thymidine). Tether lengths of two and five methylene groups in both
      series gave the highest enzyme activities in the present study. A hypothesis for
      this result is presented.

PMID- 12190324
TI  - Synthesis and transporter binding properties of 3beta-[4'-(phenylalkyl, 
      phenylalkenyl, and -phenylalkynyl)phenyl]tropane-2beta-carboxylic acid methyl
      esters: evidence of a remote phenyl binding domain on the dopamine transporter.
AB  - A series of 4'-substituted 3beta-phenyltropane-2beta-carboxylic acid methyl
      esters were synthesized and evaluated for binding at the dopamine transporter
      (DAT) in order to better define the pharmacophore for the cocaine binding site on
      the DAT. Results from the study of 3beta-[(4'-phenylalkyl)phenyl]tropane-2beta
      carboxylic acid methyl esters (5a-c and 6a,b) revealed strong evidence of a
      previously unknown remote binding domain. The 3beta-[(4'
      phenylethyl)phenyl]tropane-2beta-carboxylic acid methyl ester (5a), which has a
      two methylene linker between the 3beta-phenyl group and the remote phenyl group,
      has an IC(50) value of 5.14 nM at the DAT. The 3beta-[4'-(benzyl)phenyl] and
      3beta-[4'-(phenylpropyl)phenyl] analogues 6b and 5b, respectively, are 102- and
      68-fold less potent than 5a at the DAT. Compound 5a also has good affinity for
      the serotonin and norepinephrine transporters (K(i) = 21 and 6.5 nM,
      respectively) and is thus a nonselective monoamine uptake inhibitor.
      Electrostatic effects make a significant contribution to the DAT binding affinity
      of the 3beta-[(4'-phenylalkenyl)phenyl]tropane-2beta-carboxylic methyl esters
      (6c, 7a,b, and 8) and 3beta-[(4'-phenylalkynl)phenyl]tropane-2beta-carboxylic
      acid methyl esters (4a-e). However, the results from the DAT binding on these
      compounds suggest that there may be another binding domain even further remote
      from the 4'-position on the 3beta-phenyl group. In both cases, steric barriers
      have to be overcome before potent binding to the DAT is observed. 3beta-(4'(3
      Phenyl-1-propynyl)phenyl)tropane-2beta-carboxylic acid methyl ester (4b), with an
      IC(50) value of 1.82 nM, was the most potent compound studied. This compound
      possessed K(i) values of 1.19 and 16.5 nM for the serotonin and norepinephrine
      transporter and is thus a nonselective monoamine uptake inhibitor.

PMID- 12190326
TI  - Conformationally constrained nicotines: polycyclic, bridged, and spiro-annulated
      analogues as novel ligands for the nicotinic acetylcholine receptor.
AB  - A set of novel nicotine-related, conformationally constrained compounds,
      including tetracyclic, bridged (4), and tricyclic, spiro-annulated (5)
      structures, were synthesized in a straightforward manner and optically resolved
      in a convenient fashion with (+)- and (-)-O,O'-di-p-toluoyltartaric acids.
      Absolute configurations were determined by X-ray crystallography. These compounds
      were evaluated for their ability to displace [(3)H]cytisine in a rat forebrain
      preparation and compared to (-)-nicotine. Three substances emerged with high
      affinity in the low nanomolar range. Moreover, one of these compounds ((+)-5b)
      showed not only high binding affinity (K(i) = 4.79 nM) but also significant
      enantioselectivity over its antipode (K(i) = 148 nM), supporting the hypothesis
      that conformational restraint can lead to high-affinity ligands, which are
      stereochemically discriminated by the nicotinic acetylcholine receptor and may
      feature optimum locations of the active sites of the pharmacophore.

PMID- 12190325
TI  - Ginkgolide derivatives for photolabeling studies: preparation and pharmacological
      evaluation.
AB  - The terpene trilactones (TTLs), ginkgolides and bilobalide, are structurally
      unique constituents of Ginkgo biloba extracts, which exhibit various
      neuromodulatory properties. Although the TTLs are believed to be responsible for
      some of these effects, the specific interactions with targets in the central
      nervous system remain to be elucidated on a molecular level. Ginkgolides are
      known antagonists of the platelet-activating factor (PAF) receptor. Herein, we
      describe the first examination of the binding of native TTLs and their
      derivatives to the cloned PAF receptor, confirming that of the TTLs, ginkgolide B
      is the most potent PAF receptor antagonist. Ginkgolide derivatives carrying
      photoactivatable and fluorescent groups for the purpose of performing
      photolabeling have been prepared and evaluated using the cloned PAF receptor.
      These studies have shown that ginkgolide derivatives with aromatic
      photoactivatable substituents are potent PAF receptor antagonists with K(i)
      values of 0.09-0.79 microM and hence excellent ligands for clarifying the binding
      of ginkgolides to PAF receptor by photolabeling studies. Ginkgolide derivatives
      incorporating both fluorescent and photoactivatable groups still retained binding
      affinity to the PAF receptor and hence should be promising ligands for
      photolabeling and subsequent sequencing studies.

PMID- 12190329
TI  - Context-sensitive half-times: what are they and how valuable are they in
      anaesthesiology?
AB  - The context-sensitive half-time is the time required for blood or plasma
      concentrations of a drug to decrease by 50% after discontinuation of drug
      administration. The context-sensitive half-time often cannot be predicted by the
      elimination half-life (a measure of the time needed for actual drug metabolism or
      elimination) since it also depends on drug distribution. The context-sensitive
      half-time is a function of the duration of drug administration and may only be
      estimated by computer simulation. It is more relevant than other isolated
      pharmacokinetic parameters to understanding the kinetics of drug concentrations.
      However, understanding the kinetics of drug effect requires concomitant
      consideration of pharmacodynamics.

PMID- 12190330
TI  - Clinical pharmacokinetics of intranasal sumatriptan.
AB  - A substantial proportion of migraine patients have gastric stasis and suffer
      severe nausea and/or vomiting during their migraine attack. This may lead to
      erratic absorption from the gastrointestinal tract and make oral treatment
      unsatisfactory. For such patients, an intranasal formulation may be advantageous.
      Sumatriptan is a potent serotonin 5HT(1B/1D) agonist widely used in the treatment
      of migraine; the effectiveness of the intranasal formulation (20mg) has been well
      established in several clinical studies. This article reviews the
      pharmacokinetics of intranasal sumatriptan and includes comparisons with oral and
      subcutaneous administration. After intranasal administration, sumatriptan is
      directly and rapidly absorbed, with 60% of the maximum plasma concentration
      (C(max)) occurring at 30 minutes after administration of a single 20mg dose.
      Following intranasal administration, approximately 10% more sumatriptan is
      absorbed probably via the nasal mucosa when compared with oral administration.
      Mean C(max) after a 20mg intranasal dose is approximately 13.1 to 14.4 ng/mL,
      with median time to C(max) approximately 1 to 1.75 hours. When given as a single
      dose, intranasal sumatriptan displays dose proportionality in its extent of
      absorption and C(max) over the dose range 5 to 10mg, but not between 5 and 20mg
      for C(max). The elimination phase half-life is approximately 2 hours, consistent
      with administration by other routes. Sumatriptan is metabolised by monoamine
      oxidase (MAO; predominantly the A isozyme, MAO-A) to an inactive metabolite.
      Coadministration with a MAO-A inhibitor, moclobemide, leads to a significant
      increase in sumatriptan plasma concentrations and is contraindicated. Single-dose
      pharmacokinetics in paediatric and adolescent patients following intranasal
      sumatriptan were studied to determine the effect of changes in nasal morphology
      during growth, and of body size, on pharmacokinetic parameters. The
      pharmacokinetic profile observed in adults was maintained in the adolescent
      population; generally, factors such as age, bodyweight or height did not
      significantly affect the pharmacokinetics. In children below 12 years, C(max) is
      comparable to that seen in adolescents and adults, but total exposure (area under
      the concentration-time curve from zero to infinity) was lower in children
      compared with older patients, especially in younger children treated with 5mg.
      Clinical experience suggests that intranasal sumatriptan has some advantages over
      the tablet (more rapid onset of effect and use in patients with gastrointestinal
      complaints) or subcutaneous (noninvasive and fewer adverse events) formulations.

PMID- 12190334
TI  - Endoscopic partial adenoidectomy for children with submucous cleft palate.
AB  - OBJECTIVE: Children with submucous cleft palate who suffer from chronic nasal
      obstruction because of hypertrophic adenoids usually are not subjected to
      adenoidectomy because of the fear of postoperative velopharyngeal insufficiency.
      These patients present a therapeutic challenge because we are aware more than
      ever of the importance of normal nasal breathing and nocturnal respiration,
      especially during childhood. Our hypothesis was that transnasal endoscopic
      horizontal limited adenoidectomy may relieve nasal obstruction while preserving
      the function of the velopharyngeal valve. The objective of this study was to
      evaluate the efficacy of transnasal endoscopic horizontal partial adenoidectomy
      in patients with submucous cleft palate and adenoidal hypertrophy. SETTING:
      Patients were either referred to the outpatient clinic of the Palate Surgery Unit
      (seven patients) or were patients referred to the senior author's (Y.F.) private
      clinic. All the patients had been operated on by this senior author (Y.F.).
      PATIENTS: Ten children aged 3.5 to 13 years (six girls and four boys) with
      submucous cleft palate and hypertrophic adenoids were included in the study. All
      the patients were hyponasal and suffered nasal obstruction, loud snoring, and
      episodes of apnea. INTERVENTIONS: Endoscopic partial adenoidectomy was
      accomplished to open the lower third of the choanae. Nasal breathing was achieved
      in all the patients, and only mild snoring remained in two patients. The
      hyponasality disappeared and speech intelligibility normalized. Mild
      hypernasality developed in two patients but was still perceived as an overall
      improvement in speech. CONCLUSIONS: Transnasal endoscopic horizontal partial
      adenoidectomy may be an effective surgical method for relief of nasal obstruction
      while preserving velopharyngeal valve function in patients with submucous cleft
      palate who suffer from obstructive adenoids.

PMID- 12190332
TI  - Comprehensive survey of the relationship between serum concentration and
      therapeutic effect of amitriptyline in depression.
AB  - The relationship between serum concentration (C(s)) of amitriptyline and its
      therapeutic effect in depression has been investigated frequently over the last 3
      decades; however, the results were controversial and no consensus was reached.
      Therefore, we have performed a comprehensive survey and meta-analysis of the
      subject. All relevant literature was included, and the design of studies on the
      serum concentration-therapeutic effect relationship (SCTER) of amitriptyline was
      evaluated. Pooled original data from SCTER studies with adequate design were
      analysed by various statistical methods: regression analysis of therapeutic
      effect and C(s); comparison of the mean therapeutic effect in various ranges of
      C(s); dichotomisation of outcome and analysis according to sensitivity of
      receiver operation curves; frequency of responders and nonresponders in ranges
      determined by points of sensitivity; analysis of the distribution of C(s) in
      responders and nonresponders; logistic regression of responders and nonresponders
      with C(s) and other independent variables; calculation of effect size (g) and
      mean effect size (g(m)). Forty-five SCTER studies of amitriptyline were
      identified, and 27 studies met the minimum criteria of adequate study design.
      Inadequate study design predicted the finding of no SCTER. Analysis of the pooled
      data from studies with adequate design confirmed a therapeutic window of the sum
      of C(s) of amitriptyline and its active metabolite nortriptyline of about 80 to
      200 microg/L. A moderate and significant positive g(m) (0.538, 95% confidence
      interval 0.167 to 0.909) was calculated for treatment with C(s) within the
      therapeutic window in comparison with treatment with C(s) outside the therapeutic
      window (19 studies with adequate design and original data available, n = 583). In
      conclusion, the evidence for a biphasic SCTER of amitriptyline in depression is
      considerably improved, and the results may help to find a consensus in the
      future. However, the clinical benefit of therapeutic drug monitoring of
      amitriptyline can only be demonstrated in a controlled and randomised study.
      Furthermore, the results provide further evidence that antidepressants at optimum
      C(s) are superior to placebo in the treatment of depression.

PMID- 12190335
TI  - Fibroblast growth factor 2 induces increased calvarial osteoblast proliferation
      and cranial suture fusion.
AB  - OBJECTIVE: Craniosynostosis has been associated with fibroblast growth factors
      (FGFs) and their receptors. The purpose of this study was to quantitatively
      determine the effect of FGF2 on rat calvarial osteoblasts and a rat cranial
      suture formation model. DESIGN: Fetal rat calvarial osteoblasts were cultured
      with and without FGF2. Cell attachment and proliferation was determined by alamar
      Blue dye assay and cell morphology by toluidine-blue staining. In rat calvarial
      organ culture, postnatal day 15 rat calvariae with dura mater were placed in
      serum-free media with and without FGF2. A unique quantitative analysis of suture
      fusion was developed by obtaining measurements of suture bridging in histological
      serial sections at progressive stages of fusion. RESULTS: Attachment for cells
      treated with FGF2 was similar to control. In contrast, proliferation was higher
      for cells treated with FGF2 while maintaining an osteoblastic morphology. After 5
      days in organ culture, FGF2-treated posterior frontal sutures showed a dramatic
      increase in fusion, compared with untreated controls. This increased fusion was
      maintained throughout days 7 and 10 in culture. Also, fusion was enhanced on the
      dural side of the suture, as is normally observed in vivo, and the normal tissue
      architecture was maintained. CONCLUSIONS: These results indicate that FGF2 can
      promote rat osteoblast attachment and normal cell morphology as well as induce
      cell proliferation. In calvarial organ culture, FGF2 treatment produced an
      enhanced suture fusion. These results provide further support for a critical role
      for FGF2 in cranial suture development. These studies also present a new
      quantitative approach to evaluating the effect of suture-perturbing growth
      factors on cranial suture fusion.

PMID- 12190336
TI  - Surgical results of primary lip repair using the triangular flap method for the
      treatment of complete unilateral cleft lip and palate: a three-dimensional study
      in infants to four-year-old children.
AB  - OBJECTIVE: To evaluate morphological problems for children with complete
      unilateral cleft lip and palate (UCLP). DESIGN AND SETTING: A cross-sectional
      study was performed on 46 patients with complete UCLP at Osaka University Dental
      Hospital. PATIENTS AND PARTICIPANTS: The method was applied to three groups of
      children with UCLP (8 4-month-old infants, 18 1.5-year-old children, and 20 4
      year-old children). MAIN OUTCOME MEASURES: The three-dimensional coordinates of
      facial landmarks were extracted automatically from XYZ data sets and from photo
      images produced by an optical surface scanner. RESULTS: The intercanthal
      distance, nose width, and mouth width were closer to those of normal children in
      the older group. Deviation of the columella toward the noncleft side was smaller
      in the 4-year-old group. The angle of the nasal tip was large in all groups.
      Asymmetry of the ala was conspicuous at the upper part of the nose in the
      vertical dimension. Asymmetry of the nostril was observed in the vertical
      dimension and in the anteroposterior dimension in the 4-year-old group. The angle
      of the Cupid's bow was obtuse on the noncleft side, and the bottom of the Cupid's
      bow deviated toward the cleft side. The Cupid's bow was longer on the noncleft
      side. Protrusion of the vermilion was poor in all groups.

PMID- 12190333
TI  - Theoretical predictions of drug absorption in drug discovery and development.
AB  - The clinical development of new drugs is often terminated because of unfavourable
      pharmacokinetic properties such as poor intestinal absorption after oral
      administration. Intestinal permeability and solubility are two of the most
      important factors that determine the absorption properties of a compound.
      Efficient and reliable computational models that predict these properties as
      early as possible in drug discovery and development are therefore desirable. In
      this review, we first discuss the implementation of predictive models of
      intestinal drug permeability and solubility in drug discovery and development.
      Secondly, we discuss the mechanisms of intestinal drug permeability and
      computational methods that can be used to predict it. We then discuss factors
      influencing drug solubility and models for predicting it. We finally speculate
      that once these and other predictive computational models are implemented in drug
      discovery and development, these processes will become much more effective.
      Further, an increased fraction of drug candidates that are less likely to fail
      during clinical development will be selected.

PMID- 12190337
TI  - Change in levator veli palatini muscle activity for patients with cleft palate in
      association with placement of a speech-aid prosthesis.
AB  - OBJECTIVE: The purpose of this study was to examine whether a speech-aid
      prosthesis normalizes the activity of the levator veli palatini muscle for
      patients with cleft palate who exhibit velopharyngeal incompetence. DESIGN: Each
      subject was instructed to produce repetitions of /mu/, /u/, /pu/, /su/, and /tsu/
      and to blow with maximum possible effort. Electromyographic (EMG) activity of the
      levator veli palatini muscle was recorded with and without a hybrid speech-aid
      prosthesis in place. PARTICIPANTS: The participants were five patients with
      repaired cleft palate who were routinely wearing a hybrid speech-aid prosthesis.
      RESULTS: With the prosthesis in place, the mean value of levator activity changed
      positively in relation to oral air-pressure change during blowing. Differences in
      levator activity in relation to speech samples were similar to those in normal
      speakers. With the prosthesis in place, levator activity for speech tasks was
      less than 50% of the maximum levator activity for all subjects. The findings were
      similar to those reported previously for normal speakers. CONCLUSION: Placement
      of the prosthesis changed EMG activity levels of the levator veli palatini muscle
      to levels that are similar to normal speakers. It is possible that, with the
      increase in the differential levator activity between speech and a maximum force
      task, the velopharyngeal mechanism has a greater reserve capacity to maintain
      velopharyngeal closure compared with the no-prosthesis condition.

PMID- 12190338
TI  - Dental maturity in children with a complete bilateral cleft lip and palate.
AB  - OBJECTIVE: Dental age in children with a bilateral cleft lip and palate (BCLP)
      was assessed and compared with children without cleft. DESIGN: Dental age was
      estimated for 74 children with a complete BCLP (54 boys and 20 girls) from 364
      orthopantomograms. Nonlinear regression curves were made between 5 and 14 years
      of age for boys and girls separately. A comparison was made with a sample of
      Dutch children (91 girls and 90 boys) without oral clefts for three different age
      groups, namely 5, 9.5, and 14 years of age. SETTING: Data collection was carried
      out at the Cleft Palate Center, University Medical Center Nijmegen (The
      Netherlands). A sample from the Nijmegen Growth Study was used as a normative
      sample. RESULTS: At 5 years of age, boys with a BCLP were significantly delayed
      in dental age compared to boys without cleft. After that age, no significant
      differences in dental age were found. For girls with a BCLP, no difference in
      dental age with the girls without cleft could be found. CONCLUSION: Dental age in
      BCLP showed a tendency to be delayed at 5 years of age. At the ages of 9.5 and 14
      years of age, no differences were found. Further investigation on the development
      of individual teeth is suggested to gain more insight into the origin of this
      delay.

PMID- 12190339
TI  - Effects of cheiloplasty on maxillary dental arch development in infants with
      unilateral complete cleft lip and palate.
AB  - OBJECTIVE: To identify and analyze quantitatively the development of the
      maxillary dental arch before and after cheiloplasty. DESIGN: Prospective,
      longitudinal study of maxillary dental arch development at age of 1, 3, 6, and 12
      months. SETTING: All patients were treated at a university hospital craniofacial
      center. PATIENTS: Twenty-seven infants with nonsyndromic, unilateral complete
      cleft lip and palate. INTERVENTION: Millard's rotation-advancement cheiloplasty
      was performed between the ages of 3 and 4 months. RESULTS: The anterior portion
      of the nonclefted segment (I-G), anterior ridge length of the nonclefted segment
      (I-C), and anterior ridge length of the clefted segment (L-C') continuously
      increased from 1 to 12 months of age. The anterior cleft width (G-L), anterior
      arch depth (I perpendicular to CC'), anterior basal angle (angle GC-CC'), and
      anterior arch curature angle (angle GIC) continuously decreased after the
      cheiloplasty. CONCLUSIONS: Cheiloplasty could mold the anterior portion of the
      maxillary dental arch palatally by exerting continuous pressure.

PMID- 12190331
TI  - Mechanisms of clinically relevant drug interactions associated with tacrolimus.
AB  - The clinical management of tacrolimus, a macrolide used as immunosuppressant
      after transplantation, is complicated by its narrow therapeutic index in
      combination with inter- and intraindividually variable pharmacokinetics. As a
      substrate of cytochrome P450 (CYP) 3A enzymes and P-glycoprotein, tacrolimus
      interacts with several other drugs used in transplantation medicine, which also
      are known CYP3A and/or P-glycoprotein inhibitors and/or inducers. In clinical
      studies, CYP3A/P-glycoprotein inhibitors and inducers primarily affect oral
      bioavailability of tacrolimus rather than its clearance, indicating a key role of
      intestinal P-glycoprotein and CYP3A. There is an almost complete overlap between
      the reported clinical drug interactions of tacrolimus and those of cyclosporin.
      However, in comparison with cyclosporin, only few controlled drug interaction
      studies have been carried out, but tacrolimus drug interactions have been
      extensively studied in vitro. These results are inconsistent and are of poor
      predictive value for clinical drug interactions because of false negative
      results. P-glycoprotein regulates distribution of tacrolimus through the blood
      brain barrier into the brain as well as distribution into lymphocytes.
      Interaction of other drugs with P-glycoprotein may change tacrolimus tissue
      distribution and modify its toxicity and immunosuppressive activity. There is
      evidence that ethnic and gender differences exist for tacrolimus drug
      interactions. Therapeutic drug monitoring to guide dosage adjustments of
      tacrolimus is an efficient tool to manage drug interactions. In the near future,
      progress can be expected from studies evaluating potential pharmacokinetic
      interactions caused by herbal preparations and food components, the exact
      biochemical mechanism underlying tacrolimus toxicity, and the potential of
      inhibition of CYP3A and P-glycoprotein to improve oral bioavailability and to
      decrease intraindividual variability of tacrolimus pharmacokinetics.

PMID- 12190340
TI  - Three-dimensional analysis of facial morphology in normal Japanese children as
      control data for cleft surgery.
AB  - OBJECTIVE: This study presents an analysis of three-dimensional facial forms of
      normal Japanese children. DESIGN AND SETTING: Cross-sectional data (n = 247) were
      available from the Ikeda Public Health Center. PATIENTS AND PARTICIPANTS: Three
      groups of children (ninety-seven 4-month-old infants, fifty-four 1.5-year-old
      children, and eighty 3.5-year-old children) were analyzed using a three
      dimensional anthropometric technique. MAIN OUTCOME MEASURES: Three-dimensional
      coordinates of facial landmarks were extracted automatically from XYZ data sets
      and photo images of an optical surface scanner. RESULTS: Only minor gender
      differences were noted. Lip height was not correlated with other facial
      dimensions. There was a significant correlation between upper face, nose, and
      mouth widths. Compared with adults, the upper face width was larger
      (approximately 70% to 80% of adults) than the middle and lower parts of the face.
      Width ratios were greater than height and depth ratios. The lip height ratio,
      however, was larger than the lip width ratio, and the angle of the cupid's bow
      was more acute in children. The angle of the nose was more obtuse, particularly
      in the axial plane. CONCLUSIONS: In cleft lip surgery involving young children,
      there may be no need to consider gender differences. Some characteristic
      differences exist between children and adults, however, and normal standards for
      children would be helpful in plastic surgery.

PMID- 12190341
TI  - Relationship between primary palatal form and maxillofacial growth in Japanese
      children with unilateral cleft lip and palate: infancy to adolescence.
AB  - OBJECTIVE: The purpose of this retrospective study was to evaluate the
      relationship between the severity of maxillary defects and maxillofacial growth
      from infancy to adolescence in children with complete unilateral cleft lip and
      palate (UCLP). SUBJECTS: Thirty-one Japanese children with UCLP who had received
      cheiloplasty, palatoplasty, and orthodontic treatments at the Kyushu University
      Dental Hospital were selected. MATERIALS AND METHODS: A three-dimensional laser
      scanner was used to measure maxillary dental casts taken at cheiloplasty. Surface
      areas and volumes of the palatal tissue were calculated. Lateral cephalographs
      that were taken both at cheiloplasty and 15 years of age or over (average age
      16.5 years) were traced and digitized. Angular and linear measurements were
      calculated from the x, y-coordinates. Using correlation analyses, defects in the
      palatal tissue were compared with maxillofacial morphology both at cheiloplasty
      and in adolescence or maxillofacial growth during that time span. RESULTS: (1)
      The surface areas or volumes of the palatal tissue were significantly correlated
      with the following maxillofacial measurements at infancy and adolescence: Or
      depth; A-depth; PNS-height; ANS-height; N-Ba; S-N; S-Ba; N to P.P.; A'-Ptm'; Cd
      Pog; Cd-Gn; Cd-G; and the N-S-Ba, S-N-A, and A-N-B angles. (2) They were also
      significantly correlated with the following maxillofacial growth measures from
      infancy to adolescence: A-depth, S-Ba, and the N-S-Ba and S-N-A angles. Only the
      N-S-Ba angle showed a negative correlation. CONCLUSION: The patient who had more
      palatal tissue at cheiloplasty showed better maxillofacial growth.

PMID- 12190342
TI  - A local perspective on the initial management of children with cleft lip and
      palate by primary care physicians.
AB  - OBJECTIVE: To evaluate the frequency and referral patterns, need for continuing
      education, and information given to parents of children with cleft lip and palate
      by local primary care physicians. STUDY DESIGN: A survey was sent to primary care
      physicians from the pediatrics, family practice, and internal medicine/pediatrics
      specialties in six surrounding counties of a regional craniofacial center located
      within northeastern Ohio with a population base of 1.5 million people. Particular
      aspects of care evaluated included protocols of care, information for parents,
      referral patterns, conferences attended, and literature read. RESULTS: Nearly 30%
      of physicians had standard protocols when children are born with clefts. Eighty
      seven percent of physicians referred children within 2 weeks of diagnosis, yet
      only 48% gave referrals to a multidisciplinary team. Physicians providing team
      referrals were nearly three times as likely to attend related conferences and
      approximately four times as likely to have a set plan at the time of diagnosis of
      the cleft. Forty-nine percent of physicians gave oral information, 35% gave oral
      and written information, and 10% did not give parents information. Ninety-four
      percent of physicians gave parents the option to call with concerns.
      Pediatricians were approximately four times as likely to attend cleft conferences
      and desire continuing education updates. However, family practitioners were over
      three times as likely to give proper referrals, compared with pediatricians.
      CONCLUSION: There is a necessity to educate local primary care physicians who
      manage children with cleft lip and palate regarding cleft information for
      parents, referral guidelines, the cleft team concept, and the role of primary
      physicians.

PMID- 12190344
TI  - Onlay bone graft augmentation for refined correction of coronal synostosis.
AB  - OBJECTIVE: The primary purpose of this study was to evaluate the long-term result
      of an onlay bone graft augmentation of the supraorbital ridge at the time of
      primary correction of coronal suture synostosis. DESIGN: The study is a
      retrospective review of 62 consecutive patients treated for coronal synostosis
      from June 1991 through February 1997. The surgical technique utilized involved a
      standard bilateral fronto-orbital advancement and calvarial reshaping with the
      addition of an onlay bone graft in the supraorbital region. SETTING: All patients
      were treated at a tertiary care craniofacial center. RESULTS AND CONCLUSION: A
      total of 62 patients were treated by this technique. Fifty patients underwent
      primary correction as infants (mean age 9.8 months). An additional 12 patients
      were older (mean age 8.2 years) and were treated for residual deformity having
      previously undergone correction by another technique. Results with follow-up as
      long as 7 years demonstrate stable forehead and orbital symmetry. Complications
      identified by chart review were minimal and not directly attributable to this
      modification in surgical technique.

PMID- 12190343
TI  - Cervical root resorption in two patients with unilateral complete cleft of the
      lip and palate.
AB  - OBJECTIVE: Case reports on cervical root resorption in patients with complete
      cleft of the lip and palate are scarce. Moreover, cervical root resorption is
      sometimes diagnosed several years after a combined orthodontic and surgical
      therapy in patients with cleft. In this article a review of the literature is
      presented, and a description and the management of the cervical lesion is
      provided. An additional objective of this report is to advocate for alveolar bone
      grafting before the age of 12 years while the vulnerable cervical region of the
      teeth adjacent to the cleft defect is still protected by a thick layer of bone.

PMID- 12190345
TI  - Seventeen-year follow-up of a patient with median cleft of the lower lip,
      mandible, and tongue with flexion contracture: a case report.
AB  - PURPOSE: We present a 17-year follow-up of an unusual patient with median cleft
      of the lower lip, mandible, and tongue with a flexion contracture. CONCLUSION:
      Timing of the mandibular reconstruction needs to take into account growth of the
      mandible and masticatory function. In this case, fixation of the mandible
      performed at the age of 6 years 6 months and reconstruction carried out at 7
      years 8 months of age resulted in satisfactory occlusion and masticatory
      function.

PMID- 12190346
TI  - Microsurgical tissue transfer for rehabilitation of the patient with cleft lip
      and palate.
AB  - OBJECTIVE: Three case reports of microsurgically revascularized tissue transfer
      for secondary closure of complex oronasal fistulae in cleft lip and palate
      patients are reported. One scapular and two radial forearm flaps were used in
      that respect; the scapular flap was transferred without a skin paddle and was
      left for secondary epithelialization whereas iliac crest bone was transplanted in
      the two patients with the forearm flaps in a further surgical step. CONCLUSIONS:
      These microsurgical flaps represent solutions in selected cases of oronasal
      fistulae in patients with cleft lip and palate with extensive scarring, large
      defects, or both. Alternative free flaps of the vast spectrum available today,
      however, also deserve consideration.

PMID- 12190347
TI  - Nasoalveolar molding and gingivoperiosteoplasty verses alveolar bone graft: an
      outcome analysis of costs in the treatment of unilateral cleft alveolus.

PMID- 12190349
TI  - In the region of Bio-Bio, Chile, there is a high incidence of children suffering
      from lip fissure, cleft palate, or both.

PMID- 12190350
TI  - A piece of my mind. More stories.

PMID- 12190351
TI  - Noninvasive ventilation for acute respiratory failure.

PMID- 12190353
TI  - "Cipromania" and "superclean" homes are now increasing antibiotic resistance.

PMID- 12190352
TI  - "Palliative care" means "active care": it aims to improve quality of life.

PMID- 12190354
TI  - Effective pain treatment promotes activities.

PMID- 12190355
TI  - Postprandial hyperglycemia and risk of atherosclerosis.

PMID- 12190357
TI  - Postmarketing surveillance and black box warnings.

PMID- 12190358
TI  - Postmarketing surveillance and black box warnings.

PMID- 12190359
TI  - Postmarketing surveillance and black box warnings.

PMID- 12190360
TI  - Postmarketing surveillance and black box warnings.

PMID- 12190361
TI  - Postmarketing surveillance and black box warnings.

PMID- 12190364
TI  - Educating authors and reviewers of economic evaluations of health care.

PMID- 12190366
TI  - Exposure to dogs and cats in the first year of life and risk of allergic
      sensitization at 6 to 7 years of age.
AB  - CONTEXT: Childhood asthma is strongly associated with allergic sensitization.
      Studies have suggested that animal exposure during infancy reduces subsequent
      allergic sensitization. OBJECTIVE: To evaluate the relationship between dog and
      cat exposure in the first year of life and allergic sensitization at 6 to 7 years
      of age. DESIGN, SETTING, AND SUBJECTS: Prospective birth cohort study of healthy,
      full-term infants enrolled in a health maintenance organization in suburban
      Detroit, Mich, who were born between April 15, 1987, and August 31, 1989, and
      followed up yearly to a mean age of 6.7 years. Of 835 children initially in the
      study at birth, 474 (57%) completed follow-up evaluations at age 6 to 7 years.
      MAIN OUTCOME MEASURES: Atopy, defined as any skin prick test positivity to 6
      common aeroallergens (dust mites [Dermatophagoides farinae, D pteronyssinus],
      dog, cat, short ragweed [Ambrosia artemisiifolia], and blue grass [Poa
      pratensis]); seroatopy, defined as any positive allergen-specific IgE test result
      for the same 6 allergens or for Alternaria species. RESULTS: The prevalence of
      any skin prick test positivity (atopy) at age 6 to 7 years was 33.6% with no dog
      or cat exposure in the first year of life, 34.3% with exposure to 1 dog or cat,
      and 15.4% with exposure to 2 or more dogs or cats (P =.005). The prevalence of
      any positive allergen-specific IgE test result (seroatopy) was 38.5% with no dog
      or cat exposure, 41.2% with exposure to 1 dog or cat, and 17.9% with exposure to
      2 or more dogs or cats (P =.003). After adjustment for cord serum IgE
      concentration, sex, older siblings, parental smoking, parental asthma, bedroom
      dust mite allergen levels at 2 years, and current dog and cat ownership, exposure
      to 2 or more dogs or cats in the first year of life was associated with a
      significantly lower risk of atopy (adjusted odds ratio, 0.23; 95% confidence
      interval, 0.09-0.60) and seroatopy (adjusted odds ratio, 0.33; 95% confidence
      interval, 0.13-0.83). CONCLUSION: Exposure to 2 or more dogs or cats in the first
      year of life may reduce subsequent risk of allergic sensitization to multiple
      allergens during childhood.

PMID- 12190367
TI  - Effect of homocysteine-lowering therapy with folic acid, vitamin B12, and vitamin
      B6 on clinical outcome after percutaneous coronary intervention: the Swiss Heart
      study: a randomized controlled trial.
AB  - CONTEXT: Plasma homocysteine level has been recognized as an important
      cardiovascular risk factor that predicts adverse cardiac events in patients with
      established coronary atherosclerosis and influences restenosis rate after
      percutaneous coronary intervention. OBJECTIVE: To evaluate the effect of
      homocysteine-lowering therapy on clinical outcome after percutaneous coronary
      intervention. DESIGN, SETTING, AND PARTICIPANTS: Randomized, double-blind placebo
      controlled trial involving 553 patients referred to the University Hospital in
      Bern, Switzerland, from May 1998 to April 1999 and enrolled after successful
      angioplasty of at least 1 significant coronary stenosis (> or = 50%).
      INTERVENTION: Participants were randomly assigned to receive a combination of
      folic acid (1 mg/d), vitamin B12 (cyanocobalamin, 400 micro g/d), and vitamin B6
      (pyridoxine hydrochloride, 10 mg/d) (n = 272) or placebo (n = 281) for 6 months.
      MAIN OUTCOME MEASURE: Composite end point of major adverse events defined as
      death, nonfatal myocardial infarction, and need for repeat revascularization,
      evaluated at 6 months and 1 year. RESULTS: After a mean (SD) follow-up of 11 (3)
      months, the composite end point was significantly lower at 1 year in patients
      treated with homocysteine-lowering therapy (15.4% vs 22.8%; relative risk [RR],
      0.68; 95% confidence interval [CI], 0.48-0.96; P =.03), primarily due to a
      reduced rate of target lesion revascularization (9.9% vs 16.0%; RR, 0.62; 95% CI,
      0.40-0.97; P =.03). A nonsignificant trend was seen toward fewer deaths (1.5% vs
      2.8%; RR, 0.54; 95% CI, 0.16-1.70; P =.27) and nonfatal myocardial infarctions
      (2.6% vs 4.3%; RR, 0.60; 95% CI, 0.24-1.51; P =.27) with homocysteine-lowering
      therapy. These findings remained unchanged after adjustment for potential
      confounders. CONCLUSION: Homocysteine-lowering therapy with folic acid, vitamin
      B12, and vitamin B6 significantly decreases the incidence of major adverse events
      after percutaneous coronary intervention.

PMID- 12190368
TI  - Inflammatory biomarkers, hormone replacement therapy, and incident coronary heart
      disease: prospective analysis from the Women's Health Initiative observational
      study.
AB  - CONTEXT: Postmenopausal hormone replacement therapy (HRT) has been shown to
      elevate C-reactive protein (CRP) levels. Several inflammatory biomarkers,
      including CRP, are associated with increased cardiovascular risk. However,
      whether the effect of HRT on CRP represents a clinical hazard is unknown.
      OBJECTIVES: To assess the association between baseline levels of CRP and
      interleukin 6 (IL-6) and incident coronary heart disease (CHD) and to examine the
      relationship between baseline use of HRT, CRP, and IL-6 levels as they relate to
      subsequent vascular risk. DESIGN, SETTING, AND PARTICIPANTS: Prospective, nested
      case-control study of postmenopausal women, forming part of the Women's Health
      Initiative, a large, nationwide, observational study. Among 75 343 women with no
      history of cardiovascular disease or cancer, 304 women who developed incident CHD
      were defined as cases and matched by age, smoking status, ethnicity, and follow
      up time with 304 study participants who remained event free during a median
      observation period of 2.9 years. MAIN OUTCOME MEASURE: Incidence of first
      myocardial infarction or death from CHD. RESULTS: Median baseline levels of CRP
      (0.33 vs 0.25 mg/dL; interquartile range [IQR], 0.14-0.71 vs 0.10-0.47; P<.001)
      and IL-6 (1.81 vs 1.47 pg/mL; IQR, 1.30-2.75 vs 1.05-2.15; P<.001) were
      significantly higher among cases compared with controls. In matched analyses, the
      odds ratio (OR) for incident CHD in the highest vs lowest quartile was 2.3 for
      CRP (95% confidence interval [CI], 1.4-3.7; P for trend =.002) and 3.3 for IL-6
      (95% CI, 2.0-5.5; P for trend <.001). After additional adjustment for lipid and
      nonlipid risk factors, both inflammatory markers were significantly associated
      with a 2-fold increase in odds for CHD events. As anticipated, current use of HRT
      was associated with significantly elevated median CRP levels. However, there was
      no association between HRT and IL-6. In analyses comparing individuals with
      comparable baseline levels of either CRP or IL-6, those taking or not taking HRT
      had similar CHD ORs. In analyses stratified by HRT, we observed a positively
      graded relationship between plasma CRP levels and the OR for CHD among both users
      and nonusers of HRT across the full spectrum of baseline CRP. CONCLUSIONS: These
      prospective findings indicate that CRP and IL-6 independently predict vascular
      events among apparently healthy postmenopausal women and that HRT increases CRP.
      However, use or nonuse of HRT had less importance as a predictor of
      cardiovascular risk than did baseline levels of either CRP or IL-6.

PMID- 12190369
TI  - National vehicle emissions policies and practices and declining US carbon
      monoxide-related mortality.
AB  - CONTEXT: Carbon monoxide (CO) has been reported to contribute to more than 2000
      poisoning deaths per year in the United States. OBJECTIVES: To evaluate the
      influence of national vehicle emissions policies and practices on CO-related
      mortality and to describe 31 years (1968-1998) of CO-related deaths in the United
      States. DESIGN AND SETTING: Longitudinal trend analysis using computerized death
      data from the Centers for Disease Control and Prevention, US Census Bureau
      population data, and annual CO emissions estimates for light-duty vehicles
      provided by the US Environmental Protection Agency. MAIN OUTCOME MEASURE: All
      deaths in the US for which non-fire-related CO poisoning was an underlying or
      contributing condition, classified by intent and mechanism of death. Negative
      binomial regression was used to incorporate every year of data into estimated
      percentage changes in CO emissions and mortality rates over time. RESULTS: During
      1968-1998, CO-related mortality rates in the United States declined from 20.2
      deaths to 8.8 deaths per 1 million person-years (an estimated decline of 57.8%;
      95% confidence interval [CI], -62.4% to -52.6%). Following the introduction of
      the catalytic converter to automobiles in 1975, CO emissions from automobiles
      decreased by an estimated 76.3% of 1975 levels (95% CI, -82.0% to -70.4%) and
      unintentional motor vehicle-related CO death rates declined from 4.0 to 0.9
      deaths per 1 million person-years (an estimated decline of 81.3%; 95% CI, -84.8%
      to -77.0%). Rates of motor vehicle-related CO suicides declined from 10.0 to 4.9
      deaths per 1 million person-years (an estimated decline of 43.3%; 95% CI, -57.5%
      to -24.3%). During 1975-1996, an annual decrease of 10 g/mile of estimated CO
      emissions from automobiles was associated with a 21.3% decrease (95% CI, -24.2%
      to -18.4%) in the annual unintentional motor vehicle-related CO death rate and a
      5.9% decrease (95%CI, -10.0% to -1.8%) in the annual rate of motor vehicle
      related CO suicides. CONCLUSIONS: If rates of unintentional CO-related deaths had
      remained at pre-1975 levels, an estimated additional 11 700 motor vehicle-related
      CO poisoning deaths might have occurred by 1998. This decline in death rates
      appears to be a public health benefit associated with the enforcement of
      standards set by the 1970 Clean Air Act.

PMID- 12190370
TI  - Risk of hemolytic uremic syndrome after antibiotic treatment of Escherichia coli
      O157:H7 enteritis: a meta-analysis.
AB  - CONTEXT: The use of antibiotics for treatment of Escherichia coli O157:H7
      infection has become controversial since a recent small study found that it may
      increase the risk of hemolytic uremic syndrome (HUS). However, other larger
      studies have reported a protective effect or no association. OBJECTIVE: To
      determine whether antibiotic therapy for E coli O157:H7 enteritis increases the
      risk of HUS. DATA SOURCES: PubMed and MEDLINE computer searches were performed
      for studies published from January 1983 to February 2001 using the key words
      hemolytic uremic syndrome, risk factor, antibiotics, and Escherichia coli
      O157:H7. Reference lists of relevant publications were reviewed, and 12 experts
      in the field were contacted to identify additional reports. No language
      restrictions were applied to the search. STUDY SELECTION: Studies were included
      if they reported a series of patients with documented E coli O157:H7 enteritis,
      some of whom developed HUS; had clear definitions of HUS; and had adequate data
      delineating the relationship between antibiotic therapy and the occurrence of
      HUS. Nine of the 26 identified studies fulfilled these criteria. DATA EXTRACTION:
      Two authors (N.S. and A.S.) independently reviewed each report identified by the
      searches and recorded predetermined information relevant to the inclusion
      criteria. A pooled odds ratio was calculated using a fixed-effects model, with
      assessment of heterogeneity among the studies. DATA SYNTHESIS: The pooled odds
      ratio was 1.15 (95% confidence interval, 0.79-1.68), indicating that there does
      not appear to be an increased risk of HUS with antibiotic treatment of E coli
      O157:H7 enteritis. Incomplete reporting of data in individual studies precluded
      adjustment for severity of illness. CONCLUSION: Our meta-analysis did not show a
      higher risk of HUS associated with antibiotic administration. A randomized trial
      of adequate power, with multiple distinct strains of E coli O157:H7 represented,
      is needed to conclusively determine whether antibiotic treatment of E coli
      O157:H7 enteritis increases the risk of HUS.

PMID- 12190371
TI  - A 58-year-old man with a diagnosis of chronic lyme disease.

PMID- 12190372
TI  - A 47-year-old woman with tension-type headaches, 1 year later.

PMID- 12190373
TI  - Paradoxical effect of domestic animals on asthma and allergic sensitization.

PMID- 12190374
TI  - Antimicrobial therapy in patients with Escherichia coli O157:H7 infection.

PMID- 12190381
TI  - Macroscopic spin tunneling and quantum critical behavior of a condensate in a
      double-well potential.
AB  - In a previous work [H. Pu, W. Zhang, and P. Meystre, Phys. Rev. Lett. 87, 140405
      (2001)]], we have shown that a spinor condensate confined in a periodic or double
      well potential exhibits ferromagnetic behavior due to the magnetic dipole-dipole
      interactions between different wells, and in the absence of external magnetic
      field, the ground state has a twofold degeneracy. In this work, we demonstrate
      the possibility of observing macroscopic quantum spin tunneling between these two
      degenerate states and show how the tunneling rate critically depends on the
      strength of the transverse field.

PMID- 12190382
TI  - Spatial resolution of spin waves in an ultracold gas.
AB  - We present the first spatially resolved images of spin waves in a gas. The
      complete longitudinal and transverse spin field as a function of time and space
      is reconstructed. Frequencies and damping rates for a standing-wave mode are
      extracted and compared with theory.

PMID- 12190383
TI  - Directional "superradiant" collisions: bosonic amplification of atom pairs
      emitted from an elongated Bose-Einstein condensate.
AB  - We study spontaneous directionality in the bosonic amplification of atom pairs
      emitted from an elongated Bose-Einstein condensate, an effect analogous to
      superradiant emission of atom-photon pairs. Using a simplified model, we make
      analytic predictions regarding directional effects for both atom-atom and atom
      photon emission. These are confirmed by numerical mean-field simulations,
      demonstrating the feasibility of nearly perfect directional emission along the
      condensate axis. The dependence of the emission angle on the pump strength for
      atom-atom pairs is significantly different than for atom-photon pairs.

PMID- 12190384
TI  - Producing Bose-Einstein condensates using optical lattices.
AB  - We relate the entropies of ensembles of atoms in optical lattices to atoms in
      simple traps. We then determine which ensembles of lattice-bound atoms will
      adiabatically transform into a Bose condensate. This shows a feasible approach to
      Bose condensation without evaporative cooling.

PMID- 12190385
TI  - Broken ergodicity in a stochastic model with condensation.
AB  - We introduce a variant of the asymmetric random average process with continuous
      state variables where the maximal mass transport is restricted by a cutoff. For
      periodic boundary conditions, we show the existence of a phase transition between
      a pure high flow phase and a mixed phase, whereby the latter consists of a
      homogeneous high flow and a condensed low flow substate without translation
      invariance. The finite system alternates between these substates which both have
      diverging lifetimes in the thermodynamic limit, so ergodicity is broken in the
      infinite system. However, the scaling behavior of the lifetimes in dependence of
      the system size is different due to different underlying flipping mechanisms.

PMID- 12190387
TI  - Production of massive stable particles in inflaton decay.
AB  - We point out that inflaton decays can be a copious source of stable or long-lived
      particles chi with mass exceeding the reheat temperature T(R) but less than half
      the inflaton mass. Once higher order processes are included, this statement is
      true for any chi particle with renormalizable (gauge or Yukawa) interactions.
      This contribution to the chi density often exceeds the contribution from thermal
      chi production, leading to significantly stronger constraints on model parameters
      than those resulting from thermal chi production alone, particularly in models
      containing stable charged particles.

PMID- 12190386
TI  - Reheating as a surface effect.
AB  - We describe a new mechanism for reheating the Universe through evaporation of a
      surface charge of a fragmented inflaton condensate. We show that for a range of
      Yukawa coupling of the inflaton to the matter sector evaporation gives rise to a
      much smaller reheat temperature compared to the standard perturbative decay. As a
      consequence, reheating through a surface effect could solve the gravitino and
      moduli overproduction problem in inflationary models without fine tuning the
      Yukawa sector.

PMID- 12190388
TI  - Light bottom squark and gluino confront electroweak precision measurements.
AB  - We address the compatibility of a light sbottom (mass approximately 2-5.5 GeV)
      and a light gluino (mass approximately 12-16 GeV) with electroweak precision
      measurements. Such light particles have been suggested to explain the observed
      excess in the b quark production cross section at the Tevatron. The electroweak
      observables may be affected by the sbottom and gluino through the supersymmetric
      QCD (SUSY-QCD) corrections to the Zbb vertex. We examine, in addition to the SUSY
      QCD corrections, the gauge boson propagator corrections from the stop which are
      allowed to be light from the SU(2)(L) symmetry. We find that this scenario is
      strongly disfavored from electroweak precision measurements.

PMID- 12190389
TI  - Rho(0) meson production in the pp-->pppi(+)pi(-) reaction at 3.67 GeV/c.
AB  - Total and differential cross sections for the exclusive reaction pp-->pp rho
      observed via the pi(+)pi(-) decay channel have been measured at p(beam)=3.67
      GeV/c. The observed total meson production cross section is determined to be
      (23.4+/-0.8+/-8) mu b and is significantly lower than typical cross sections used
      in model calculations for heavy-ion collisions. The differential cross sections
      measured indicate a strong anisotropy (approximately cos(theta(CM)(rho)) in the
      rho(0) meson production.

PMID- 12190392
TI  - Dynamical scaling law for jet tomography.
AB  - Medium modifications of parton fragmentation provide a novel tomographic tool for
      the study of the hot and dense matter created in ultrarelativistic nucleus
      nucleus collisions. Their quantitative analysis, however, is complicated by the
      strong dynamical expansion of the collision region. Here we establish for the
      multiple scattering induced gluon radiation spectrum a scaling law which relates
      medium effects in a collision of arbitrary dynamical expansion to that in an
      equivalent static scenario. Based on this scaling, we calculate for typical
      kinematical values of the RHIC and LHC heavy ion programming medium-modified
      fragmentation functions for collisions with realistic dynamical expansion.

PMID- 12190393
TI  - Mesoscopic molecular ions in Bose-Einstein condensates.
AB  - We study the possible formation of large (mesoscopic) molecular ions in an
      ultracold degenerate bosonic gas doped with charged particles (ions). We show
      that the polarization potentials produced by the ionic impurities are capable of
      capturing hundreds of atoms into loosely bound states. We describe the
      spontaneous formation of these hollow molecular ions via phonon emission and
      suggest an optical technique for coherent stimulated transitions of condensate
      atoms into a specific bound state. These results open up new possibilities for
      manipulating tightly confined ensembles.

PMID- 12190394
TI  - Oscillations in the double-photoionization cross section of Li near threshold.
AB  - The threshold region of the double-photoionization cross section of lithium was
      investigated using monochromatized synchrotron radiation and ion time-of-flight
      spectrometry. While the overall energy dependence can be described by the Wannier
      power law, we found oscillations in the cross section which are in good agreement
      with a modulated threshold law as proposed by Temkin [Phys. Rev. Lett. 49, 365
      (1982)]]. This behavior may be due to the unequal binding energies of the
      electrons involved in the double-photoionization process.

PMID- 12190395
TI  - Axialization of laser cooled magnesium ions in a penning trap.
AB  - We report the first demonstration of the axialization of laser cooled ions in a
      Penning trap. Axialization involves the application of a small radial quadrupole
      drive which couples the cyclotron and magnetron motions. This enhances the laser
      cooling, allowing tighter confinement of the ions to the central axis of the trap
      than is otherwise possible. Using an intensified charge-coupled device (ICCD)
      camera we have imaged the axialization process for the first time. For a single
      ion, we recorded a large decrease of the magnetron amplitude corresponding to a
      reduction in ion temperature of approximately 2 orders of magnitude to an upper
      limit of order 10 mK. We have discovered dynamics specific to the laser cooled
      system which depend critically on the axial drive frequency and amplitude.

PMID- 12190396
TI  - Longitudinal focusing and cooling of a molecular beam.
AB  - A neutral polar molecule experiences a force in an inhomogeneous electric field.
      This electric field can be designed such that a beam of polar molecules is
      exposed to a harmonic potential in the forward direction. In this potential the
      longitudinal phase-space distribution of the ensemble of molecules is rotated
      uniformly. This property is used to longitudinally focus a pulsed beam of ammonia
      molecules and to produce a beam with a longitudinal velocity spread of 0.76 m/s,
      corresponding to a temperature of 250 mu K.

PMID- 12190397
TI  - Giant resonances in cold electron scattering by CS(2).
AB  - Experimental data are presented for the scattering of cold electrons by CS2, for
      both integral and backward scattering, between a few meV and a few hundred meV
      impact energy. Giant resonances with cross sections in excess of 50 A(2) are
      observed below 100 meV, associated with the transient formation of CS(-)(2) at 15
      meV and with the bend and symmetric stretch of CS(2) at thresholds of 49 and 82
      meV, respectively. The resonance at 49 meV is 2 orders of magnitude greater in
      cross section than a dipole impulsive model predicts. These structures are
      superimposed on a sharp rise in the scattering cross section at low energy, which
      may be attributed to virtual state scattering.

PMID- 12190398
TI  - Excitation in ion-atom collisions inside subfemtosecond laser pulses.
AB  - We discuss new excitation mechanisms in energetic ion-atom collisions embedded in
      short laser pulses. For comparable duration and strength of the pulse and
      collisional interaction, the laser field will probe and modify the interaction
      between projectile and target. Coherence effects emerge, insight into reaction
      dynamics is gained, and new dynamical features are discovered. As an example, we
      show (i) how a propensity rule for s-p excitation can be dramatically changed,
      and (ii) how the presence of the laser pulse modifies the ionization process in
      ion-atom collisions.

PMID- 12190399
TI  - Manipulating ion-atom collisions with coherent electromagnetic radiation.
AB  - Laser-assisted ion-atom collisions are considered in terms of a nonperturbative
      quantum mechanical description of the electronic motion. It is shown for the
      system He(2+) - H at 2 keV/amu that the collision dynamics depend strongly on the
      initial phase of the laser field and the applied wavelength. Whereas electronic
      transitions are caused by the concurrent action of the field and the projectile
      ion at relatively low frequencies, they can be separated into modified
      collisional capture and field ionization events in the region above the one
      photon ionization threshold.

PMID- 12190390
TI  - Midrapidity Lambda and Lambda(macro) production in Au+Au collisions at the square
      root of [s(NN)]=130 GeV.
AB  - We report the first measurement of strange (Lambda) and antistrange (Lambda
      macro) baryon production from square root of [s(NN)]=130 GeV Au+Au collisions at
      the Relativistic Heavy Ion Collider (RHIC). Rapidity density and transverse mass
      distributions at midrapidity are presented as a function of centrality. The yield
      of Lambda and Lambda; hyperons is found to be approximately proportional to the
      number of negative hadrons. The production of Lambda; hyperons relative to
      negative hadrons increases very rapidly with transverse momentum. The magnitude
      of the increase cannot be described by existing hadronic string fragmentation
      models alone.

PMID- 12190400
TI  - Centrifugal electron-ion recombination.
AB  - Transient electric-field pulses have been used to stimulate electron/ion
      recombination in a low density plasma in the presence of a static electric field.
      The measured recombination rates exhibit a strong dependence on the relative
      orientation of the pulsed and static fields. For weak pulses, the recombination
      rate is significantly higher for orthogonal as opposed to parallel or
      antiparallel field configurations. The enhanced recombination rate is attributed
      to the dynamic stabilization of high-m Rydberg levels that are populated during
      the pulse. Classical simulations confirm the importance of angular momentum
      rather than energy transfer.

PMID- 12190401
TI  - Primary populations of metastable antiprotonic (4)He and (3)He atoms.
AB  - Initial distributions of metastable antiprotonic (4)He and (3)He atoms over
      principal (n) and angular momentum (l) quantum numbers have been deduced using
      laser spectroscopy experiments. The regions n = 37-40 and n = 35-38 in the two
      atoms account for almost all of the observed fractions [(3.0 +/- 0.1)% and (2.4
      +/- 0.1)%] of antiprotons captured into metastable states.

PMID- 12190391
TI  - Measurement of Lambda and Lambda(macro) particles in Au+Au collisions at the
      square root of S(NN) = 130 GeV.
AB  - We present results on the measurement of Lambda and Lambda(macro) production in
      Au+Au collisions at square root of (S (NN) = 130 GeV with the PHENIX detector at
      the Relativistic Heavy Ion Collider. The transverse momentum spectra were
      measured for minimum bias and for the 5% most central events. The Lambda;/Lambda
      ratios are constant as a function of p(T) and the number of participants. The
      measured net Lambda density is significantly larger than predicted by models
      based on hadronic strings (e.g., HIJING) but in approximate agreement with models
      which include the gluon-junction mechanism.

PMID- 12190402
TI  - Direct measurement of the photon statistics of a triggered single photon source.
AB  - We studied intensity fluctuations of a single photon source relying on the pulsed
      excitation of the fluorescence of a single molecule at room temperature. We
      directly measured the Mandel parameter Q(T) over 4 orders of magnitude of
      observation time scale T by recording every photocount. On time scale of a few
      excitation periods, sub-Poissonian statistics is clearly observed and the
      probablility of two-photons events is 10 times smaller than Poissonian pulses. On
      longer times, blinking in the fluorescence, due to the molecular triplet state,
      produces an excess of noise.

PMID- 12190403
TI  - Electrodynamics of metallic photonic crystals and the problem of left-handed
      materials.
AB  - An analytical theory of low frequency electromagnetic waves in metallic photonic
      crystals with a small volume fraction of a metal is presented. The evidence for
      such waves has been obtained recently by experiments and computations. The cutoff
      frequency of these waves, omega(0), is studied. An analytical expression for the
      permittivity epsilon is obtained and shown to be negative below omega(0). If the
      crystal is embedded into a medium with a negative mu, there are no propagating
      modes at any frequency. Thus, such a compound system is not a left-handed
      material (LHM). The recent experimental results on the LHM are discussed.

PMID- 12190405
TI  - Standard radiation spectrum of relativistic electrons: beyond the synchrotron
      approximation.
AB  - Radiation emitted by an electron in arbitrary, extreme relativistic motion, has
      been described for the first time in terms of a standard spectrum of
      nonsynchrotron type. Ultimately, such a nonsynchrotron spectrum is dependent not
      only on instantaneous trajectory curvature, but also upon its first two time
      derivatives and helicity, to provide a basic correction to the synchrotron
      approximation (SA). A strong deviation from SA has been predicted for above GeV
      electrons in oriented crystals.

PMID- 12190404
TI  - Avalanche dynamics in wet granular materials.
AB  - We have studied the dynamics of avalanching wet granular media in a rotating drum
      apparatus. Quantitative measurements of the flow velocity and the granular flux
      during avalanches allow us to characterize novel avalanche types unique to wet
      media. We also explore the details of viscoplastic flow (observed at the highest
      liquid contents) in which there are lasting contacts during flow, leading to
      coherence across the entire sample. This coherence leads to a velocity
      independent flow depth at high rotation rates and novel robust pattern formation
      in the granular surface.

PMID- 12190406
TI  - Experimental study of isotope scaling of ion thermal transport.
AB  - The wide divergence between most theoretical predictions of isotopic mass scaling
      of transport and tokamak experimental results motivated a basic physics
      experiment in the Columbia Linear Machine [R. Scarmozzino, A. K. Sen, and G. A.
      Navratil, Phys. Rev. Lett. 57, 1729 (1986)]]. The experiments on ion thermal
      conductivity due to ion temperature gradient-driven slab modes are performed
      using two different gases: hydrogen and deuterium. The results indicate inverse
      dependence of ion thermal conductivity on the isotope mass close to K(radially)
      approximately A(-0.5)(i). This is similar to the tokamak results, but in stark
      contradiction to most present theoretical models.

PMID- 12190407
TI  - Hall magnetic shocks in plasma current layers.
AB  - We present new analytical and numerical results of the dynamics of reversed field
      current layers in the Hall limit (i.e., characteristic length scales smaller than
      the ion inertial length). A rapid, localized thinning of the current layer leads
      to the generation of a nonlinear, shocklike structure that propagates in the B x
      inverted Delta(n) direction. This magnetic structure is self-supportive and can
      lead to a nonlocal thinning of the current layer and the release of magnetic
      energy.

PMID- 12190408
TI  - Axial magnetic fields in relativistic self-focusing channels.
AB  - Based on an improved cavitation model for the electron dynamics, an exact
      analysis is presented of the generation of axial magnetic fields in the
      relativistic self-focusing channels produced by circularly polarized light in
      plasmas. Two kinds of waveguiding structures are considered: single-channel
      waveguides and plasma filaments surrounded by a light field. It is found that due
      to large electron density gradients in the cavitation plasma, magnetic fields of
      megagauss values with opposite directions separated by a neutral sheet, where the
      magnetic field passes through zero, can be produced.

PMID- 12190409
TI  - X-ray imaging measurements of capsule implosions driven by a Z-pinch dynamic
      hohlraum.
AB  - The radiation and shock generated by impact of an annular tungsten Z-pinch plasma
      on a 10-mm diam 5-mg/cc CH(2) foam are diagnosed with x-ray imaging and power
      measurements. The radiative shock was virtually unaffected by Z-pinch plasma
      instabilities. The 5-ns-duration approximately 135-eV radiation field imploded a
      2.1-mm-diam CH capsule. The measured radiation temperature, shock radius, and
      capsule radius agreed well with computer simulations, indicating understanding of
      the main features of a Z-pinch dynamic-hohlraum-driven capsule implosion.

PMID- 12190410
TI  - Interaction of first and second sound in solid (4)He: properties of a possible
      Bose condensate.
AB  - A previous experiment in this laboratory found that the addition of a few tens of
      parts per 10(6) of (3)He impurities to solid (4)He crystals resulted in a phase
      transition below 200 mK. In the experiment described here the interaction of
      acoustic waves with waves generated by heat pulses is measured and shows that
      there is an energy gap in the excitations of the high temperature phase and that
      coherent waves are carried by nonphonon excitations at the lowest temperatures.

PMID- 12190411
TI  - Impulsive fracture of silicon by elastic surface pulses with shocks.
AB  - During nonlinear evolution of surface acoustic waves (SAWs) stress increases with
      propagation, and may cause fracture of brittle materials. This effect was used to
      evaluate the strength of crystalline silicon with respect to impulsive load in
      the nanosecond time scale without using seed cracks. Short SAW pulses propagating
      in the [11(macro)2] direction on the Si(111) plane induce fracture at
      significantly lower SAW amplitudes than the mirror symmetric wave propagating in
      the [112(macro)] direction. This effect is explained by the differences in
      elastic nonlinearity of the two propagation directions.

PMID- 12190412
TI  - Nonuniversal ordering of spin and charge in stripe phases.
AB  - We study the interplay of topological excitations in stripe phases: charge
      dislocations, charge loops, and spin vortices. In two dimensions these defects
      interact logarithmically on large distances. Using a renormalization-group
      analysis in the Coulomb-gas representation of these defects, we calculate the
      phase diagram and the critical properties of the transitions. Depending on the
      interaction parameters, spin and charge order can disappear at a single
      transition or in a sequence of two transitions (spin-charge separation). These
      transitions are nonuniversal with continuously varying critical exponents. We
      also determine the nature of the points where three phases coexist.

PMID- 12190413
TI  - Shearing a glassy material: numerical tests of nonequilibrium mode-coupling
      approaches and experimental proposals.
AB  - The predictions of a nonequilibrium schematic mode-coupling theory developed to
      describe the nonlinear rheology of soft glassy materials have been numerically
      tested in a sheared binary Lennard-Jones mixture. In this Letter, we focus on the
      existence, behavior, and properties of an effective temperature T(eff) for the
      slow modes of the fluid, as defined from a generalized fluctuation-dissipation
      theorem. New, simple experimental protocols to access T(eff) are proposed, and
      one such experiment is numerically performed. Our results give strong support to
      the thermodynamic interpretation of T(eff) and make it experimentally accessible
      in a very direct way.

PMID- 12190414
TI  - Effective temperatures of a driven system near jamming.
AB  - Fluctuations in a model of a sheared, zero-temperature foam are studied
      numerically. Five different quantities that independently reduce to the true
      temperature in an equilibrium thermal system are calculated. One of the
      quantities is calculated up to an unknown coefficient. The other four quantities
      have the same value and all five have the same shear-rate dependence. These
      results imply that statistical mechanics is useful for the system even though it
      is far from thermal equilibrium.

PMID- 12190415
TI  - Properties of cage rearrangements observed near the colloidal glass transition.
AB  - We use confocal microscopy to study particle motion in colloidal systems. Near
      the glass transition, motion is inhibited, as particles spend time trapped in
      transient "cages" formed by neighboring particles. We measure the cage sizes and
      lifetimes, which, respectively, shrink and grow as the glass transition
      approaches. Cage rearrangements are more prevalent in regions with lower
      concentrations and higher disorder. Neighboring rearranging particles typically
      move in parallel directions, although a nontrivial fraction moves in antiparallel
      directions, usually from particle pairs with initial separations corresponding to
      local maxima and minima of the pair correlation function g(r), respectively.

PMID- 12190416
TI  - What controls the thickness of wetting layers near bulk criticality?
AB  - We study the thickness of wetting layers in the binary-liquid mixture cyclohexane
      methanol. Far from the bulk critical point, the wetting layer thickness is
      independent of temperature, resulting from the competition between van der Waals
      and gravitational forces. Upon approaching the bulk critical temperature [t=(T(c)
      T)/T(c)-->0], we observe that the wetting layer thickness diverges as t(-beta)
      with effective critical exponent beta=0.23+/-0.06. This is characteristic of a
      broad, intermediate scaling regime for the crossover from van der Waals wetting
      to critical scaling. We predict beta=beta/3 approximately 0.11, with beta the
      usual bulk-order parameter critical exponent, showing a small but significant
      difference with experiment.

PMID- 12190417
TI  - Spontaneous roughening: fundamental limits in Si(100) halogen etch processing.
AB  - A dynamical scanning tunneling microscopy and density functional theory study of
      the thermodynamic stability of halogen-terminated Si(100) surfaces is presented.
      Significant steric repulsion is shown to exist on all halogen-terminated Si(100)
      surfaces. This repulsion is the driving force for a roughening phenomenon, which
      is favored for all halogens except fluorine. Since roughening is an intrinsic
      property of these surfaces, it sets a lower bound on the atomic scale perfection
      that can be achieved using halogen etch processing.

PMID- 12190418
TI  - Role of subsurface oxygen in oxide formation at transition metal surfaces.
AB  - We present a density-functional theory trend study addressing the incorporation
      of oxygen into the basal plane of the late 4d transition metals (TMs) from Ru to
      Ag. Occupation of subsurface sites is always connected with a significant
      distortion of the host lattice, rendering it initially less favorable than on
      surface chemisorption. Penetration starts only after a critical coverage
      theta(c), which is lower for the softer metals towards the right of the TM
      series. The computed theta(c) are found to be very similar to those above which
      the bulk oxide phase becomes thermodynamically more stable, thus suggesting that
      the initial incorporation of O actuates the formation of a surface oxide on TM
      surfaces.

PMID- 12190419
TI  - Exchangelike effects for closed-shell adsorbates: interface dipole and work
      function.
AB  - Based on detailed theoretical analyses, we present, for the first time, direct
      evidence that the significant interface dipole commonly observed for atoms and
      molecules physisorbed on metal surfaces originates from exchangelike effects. In
      the case of Xe, previously proposed contributions from chemical interactions do
      not play a significant role.

PMID- 12190420
TI  - Nonequilibrium statistical mechanics of mixed quantum classical ensembles:
      application to noncontact atomic force microscopy.
AB  - Using the nonequilibrium statistical operator method, we suggest a new general
      method of treating dynamics of a combined system consisting of interacting
      classical and quantum parts. The method is illustrated on the tip dynamics in the
      noncontact atomic force microscopy (NC-AFM) where a macroscopic tip interacts
      with a quantum microscopic system (the surface and the nanotip). The derived
      general equation of motion for the tip and the Fokker-Planck equation, applicable
      even at low temperatures, contain memory effects and a friction term which should
      (at least partially) be responsible for the observed energy dissipation in NC-AFM
      experiments.

PMID- 12190421
TI  - Laser ablation condensation of alpha-PbO(2)-type TiO(2).
AB  - A high-pressure phase of TiO(2) with an alpha-PbO(2)-type structure has been
      synthesized via very energetic Nd-YAG laser pulse irradiation of oxygen-purged Ti
      target. The nanometer-size alpha-PbO(2)-type particles were (11;0), (010), and
      (001) faceted but the larger ones were spherical. The combined effects of rapid
      heating and cooling, the nanophase effect, and dense surfaces account for the
      formation of coherently strained alpha-PbO(2) particles. The refined cell volume
      indicated a considerable residual stress to stabilize the dense structure to
      ambient condition.

PMID- 12190422
TI  - Role of surface plasmons in the decay of image-potential States on silver
      surfaces.
AB  - The combined effect of single-particle and collective surface excitations in the
      decay of image-potential states on Ag surfaces is investigated, and the origin of
      the long-standing discrepancy between experimental measurements and previous
      theoretical predictions for the lifetime of these states is elucidated. Although
      surface-plasmon excitation had been expected to reduce the image-state lifetime,
      we demonstrate that the subtle combination of the spatial variation of s-d
      polarization in Ag and the characteristic nonlocality of many-electron
      interactions near the surface yields surprisingly long image-state lifetimes, in
      agreement with experiment.

PMID- 12190423
TI  - Excitonic optical spectrum of semiconductors obtained by time-dependent density
      functional theory with the exact-exchange kernel.
AB  - Applying a novel exact-exchange (EXX) approach within time-dependent density
      functional theory, we obtained the optical absorption spectrum of bulk silicon in
      good agreement with experiments including excitonic features. Analysis of the EXX
      kernel shows that inclusion of the Coulomb coupling of electron-hole pairs and
      the correct long-wavelength behavior in the kernel is crucial for the proper
      description of excitonic effects in semiconductors.

PMID- 12190424
TI  - Relevance of inter-composite-fermion interaction to the edge Tomonaga-Luttinger
      liquid.
AB  - It is shown that Wen's effective theory correctly describes the Tomonaga
      Luttinger liquid at the edge of a system of noninteracting composite fermions.
      However, the weak residual interaction between composite fermions is found to be
      a relevant perturbation. The filling factor dependence of the Tomonaga-Luttinger
      parameter is estimated for interacting composite fermions in a microscopic
      approach and satisfactory agreement with experiment is achieved. It is suggested
      that the electron field operator may not have a simple representation in the
      effective one-dimensional theory.

PMID- 12190425
TI  - Persistent current in superconducting nanorings.
AB  - The superconductivity in very thin rings is suppressed by quantum phase slips. As
      a result, the amplitude of the persistent current oscillations with flux becomes
      exponentially small, and their shape changes from sawtooth to a sinusoidal one.
      We reduce the problem of low-energy properties of a superconducting nanoring to
      that of a quantum particle in a sinusoidal potential and show that the dependence
      of the current on the flux belongs to a one-parameter family of functions
      obtained by solving the respective Schrodinger equation with twisted boundary
      conditions.

PMID- 12190426
TI  - Classical properties of low-dimensional conductors: giant capacitance and non
      ohmic potential drop.
AB  - The electrical field arising around an inhomogeneous conductor when an electrical
      current passes through it is not screened, as distinct from 3D conductors, in low
      dimensional conductors. As a result, the electrical field depends on the global
      distribution of the conductivity sigma(x) rather than on the local value of it,
      inhomogeneities of sigma(x) produce giant capacitances C(omega) that show
      frequency dependence at relatively low omega, and electrical fields develop in
      vast regions around the inhomogeneities of sigma(x). A theory of these phenomena
      is presented for 2D conductors.

PMID- 12190427
TI  - Strain-induced quantum ring hole states in a gated vertical quantum dot.
AB  - We have experimentally investigated the hole states in a gated vertical strained
      Si/SiGe quantum dot. We demonstrate the inhomogeneous-strain relaxation on the
      lateral surface creates a ringlike potential near the perimeter of the dot, which
      can confine hole states exhibiting quantum ring characteristics. The
      magnetotunneling spectroscopy exhibits the predicted periodicity of energy states
      in phi/phi(0), but the magnitude of the energy shifts is larger than predicted by
      simple ring theory. Our results suggest a new way to fabricate and study quantum
      ring structures.

PMID- 12190428
TI  - Zero-field satellites of a zero-bias anomaly.
AB  - Spin-orbit (SO) splitting, +/-omega(SO), of the electron Fermi surface in two
      dimensional systems manifests itself in the interaction-induced corrections to
      the tunneling density of states, nu(epsilon). Namely, in the case of a smooth
      disorder, it gives rise to the satellites of a zero-bias anomaly at energies
      epsilon = +/-2 omega(SO). Zeeman splitting, +/-omega(Z), in a weak parallel
      magnetic field causes a narrow plateau of a width delta epsilon = 2 omega(Z) at
      the top of each sharp satellite peak. As omega(Z) exceeds omega(SO), the SO
      satellites cross over to the conventional narrow maxima at epsilon = +/-2
      omega(Z) with SO-induced plateaus delta epsilon = 2 omega(SO) at the tops.

PMID- 12190429
TI  - Magneto-optical study of the superconducting gap of MgB(2) single crystals.
AB  - We present magneto-optical reflectivity results in the basal plane of the
      hexagonal MgB(2). The data were collected on a mosaic of MgB(2) single crystals
      with T(c)=38 K from the ultraviolet down to the far infrared as a function of
      temperature and magnetic field oriented along the c axis. In the far infrared,
      there is a clear signature of the superconducting gap with a gap ratio 2
      Delta/k(B)T(c) approximately 1.2, well below the weak-coupling value. The gap is
      suppressed in an external magnetic field, which is a function of temperature. We
      extract the upper critical field H(c2) along the c axis. The temperature
      dependence of H(c2) is compatible with the Helfand-Werthamer behavior.

PMID- 12190430
TI  - Peak effect in single crystal MgB(2) superconductor for H axially c-axis.
AB  - We have studied the phase diagram of the MgB(2) superconductor using a single
      crystal for the H parallel c-axis. For the first time we report the existence of
      peak effect in the screening current in the MgB(2) for the H parallel c-axis. In
      the magnetic field regime 10<H<13.5 kOe the local fundamental diamagnetic moment
      displays a very narrow diamagnetic step. For higher fields this step is
      transformed to a peak (peak effect) and, finally, for H<10 kOe the diamagnetic
      step is transformed to a gradual transition.

PMID- 12190431
TI  - Symmetrical temperature-chaos effect with positive and negative temperature
      shifts in a spin glass.
AB  - Aging in a Heisenberg-like spin glass Ag(11 at. % Mn) is investigated by
      measurements of the zero-field-cooled magnetic relaxation at a constant
      temperature after small temperature shifts absolute value of Delta T/T(g) <
      0.012. A crossover from fully accumulative to nonaccumulative aging is observed,
      and by converting time scales to length scales using the logarithmic growth law
      of the droplet model, we find quantitative evidence that positive and negative
      temperature shifts cause an equivalent restart of aging (rejuvenation) in terms
      of dynamical length scales. This result supports the existence of a unique
      overlap length between a pair of equilibrium states in the spin-glass system.

PMID- 12190432
TI  - Fourth-order magnetic anisotropy and tunnel splittings in Mn(12) from spin-orbit
      vibron interactions.
AB  - From density-functional-theory based methods, we calculate the vibrational
      spectrum of the Mn(12)O(12)(COOH)(16)(H(2)O)(4) molecular magnet. Calculated
      infrared intensities are in accord with experimental studies. There have been no
      ab initio attempts at determining which interactions account for the fourth-order
      anisotropy. We show that vibrationally induced distortions of the molecule
      contribute to the fourth-order anisotropy Hamiltonian and that the magnitude and
      sign of the effect (-6.2 K) is in good agreement with all experiments.
      Vibrationally induced tunnel splittings in isotopically pure and natural samples
      are predicted.

PMID- 12190433
TI  - Infrared probe of itinerant ferromagnetism in Ga(1-x)Mn(x)As.
AB  - The doping and temperature dependence of the complex conductivity is determined
      for the ferromagnetic semiconductor Ga(1-x)Mn(x)As. A broad resonance develops
      with Mn doping at an energy scale of approximately 200 meV, well within the GaAs
      band gap. Possible origins of this feature are explored in the context of a Mn
      induced impurity band and intervalence band transitions. From a sum rule analysis
      of the conductivity data the effective mass of the itinerant charge carriers is
      found to be at least a factor of 3 greater than what is expected for hole doped
      GaAs. In the ferromagnetic state a significant decrease in the effective mass is
      observed, demonstrating the role played by the heavy carriers in inducing
      ferromagnetism in this system.

PMID- 12190434
TI  - Replica field theory and renormalization group for the Ising spin glass in an
      external magnetic field.
AB  - We use the generic replica symmetric cubic field theory to study the transition
      of short-range Ising spin glasses in a magnetic field around the upper critical
      dimension. A novel fixed point is found from the application of the
      renormalization group. In the spin-glass limit, this fixed point governs the
      critical behavior of a class of systems characterized by a single cubic
      parameter. For this universality class, the spin-glass susceptibility diverges at
      criticality, whereas the longitudinal mode remains massive. The third mode,
      however, behaves unusually. The physical consequences of this unusual behavior
      are discussed, and a comparison with the conventional de Almeida-Thouless
      scenario is presented.

PMID- 12190435
TI  - Zener polaron ordering in half-doped manganites.
AB  - We have refined the crystal structures of a Pr(0.60)Ca(0.40)MnO(3) single crystal
      from neutron diffraction data. The result at low temperature gives a
      superstructure that cannot be interpreted as Mn(3+)/Mn(4+) charge ordering. The
      pattern of atom displacements suggests the trapping of electrons within pairs of
      Mn sites, involving both a local double exchange and a polaronic-like distortion.
      The two mechanisms act together to form vibronic localized electronic states:
      Zener polarons. We have confirmed this picture by showing how it elucidates the
      unconventional paramagnetic behavior of half-doped manganites.

PMID- 12190436
TI  - Coherence length of excitons in a semiconductor quantum well.
AB  - We report on the first experimental determination of the coherence length of
      excitons in semiconductors using the combination of spatially resolved
      photoluminescence with phonon sideband spectroscopy. The coherence length of
      excitons in ZnSe quantum wells is determined to be 300-400 nm, about 25-30 times
      the exciton de Broglie wavelength. With increasing exciton kinetic energy, the
      coherence length decreases slowly. The discrepancy between the coherence lengths
      measured and calculated by considering only the acoustic-phonon scattering
      suggests an important influence of static disorder.

PMID- 12190437
TI  - Conformational dynamics of photoexcited conjugated molecules.
AB  - Time-dependent photoexcitation and optical spectroscopy of pi-conjugated
      molecules is described using a new method for the simulation of excited state
      molecular dynamics in extended molecular systems with sizes up to hundreds of
      atoms. Applications are made to poly(p-phenylene vinylene) oligomers. Our
      analysis shows self-trapping of excitations on about six repeat units in the
      course of photoexcitation relaxation, identifies specific slow (torsion) and fast
      (bond-stretch) nuclear motions strongly coupled to the electronic degrees of
      freedom, and predicts spectroscopic signatures of molecular conformations.

PMID- 12190438
TI  - Domain wall creep in epitaxial ferroelectric Pb(Zr(0.2)Ti(0.08)O(3) thin films.
AB  - Ferroelectric switching and nanoscale domain dynamics were investigated using
      atomic force microscopy on monocrystalline Pb(Zr(0.2)Ti(0.8))O(3) thin films.
      Measurements of domain size versus writing time reveal a two-step domain growth
      mechanism, in which initial nucleation is followed by radial domain wall motion
      perpendicular to the polarization direction. The electric field dependence of the
      domain wall velocity demonstrates that domain wall motion in ferroelectric thin
      films is a creep process, with the critical exponent mu close to 1. The
      dimensionality of the films suggests that disorder is at the origin of the
      observed creep behavior.

PMID- 12190439
TI  - Conditions for the local manipulation of Gaussian states.
AB  - We present a general necessary and sufficient criterion for the possibility of a
      state transformation from one mixed Gaussian state to another of a bipartite
      continuous-variable system with two modes. The class of operations that will be
      considered is the set of local Gaussian completely positive trace-preserving
      maps.

PMID- 12190440
TI  - Implementation of universal quantum gates based on nonadiabatic geometric phases.
AB  - We propose an experimentally feasible scheme to achieve quantum computation based
      on nonadiabatic geometric phase shifts, in which a cyclic geometric phase is used
      to realize a set of universal quantum gates. Physical implementation of this set
      of gates is designed for Josephson junctions and for NMR systems. Interestingly,
      we find that the nonadiabatic phase shift may be independent of the operation
      time under appropriate controllable conditions. A remarkable feature of the
      present nonadiabatic geometric gates is that there is no intrinsic limitation on
      the operation time.

PMID- 12190441
TI  - Micro-optical realization of arrays of selectively addressable dipole traps: a
      scalable configuration for quantum computation with atomic qubits.
AB  - We experimentally demonstrate novel structures for the realization of registers
      of atomic qubits: We trap neutral atoms in one- and two-dimensional arrays of far
      detuned dipole traps obtained by focusing a red-detuned laser beam with a
      microfabricated array of microlenses. We are able to selectively address
      individual trap sites due to their large lateral separation of 125 microm. We
      initialize and read out different internal states for the individual sites. We
      also create two interleaved sets of trap arrays with adjustable separation, as
      required for many proposed implementations of quantum gate operations.

PMID- 12190442
TI  - Quantum information is incompressible without errors.
AB  - A classical random variable can be faithfully compressed into a sequence of bits
      with its expected length lying within one bit of Shannon entropy. We generalize
      this variable-length and faithful scenario to the general quantum source
      producing mixed states rho(i) with probability p(i). In contrast to the classical
      case, the optimal compression rate in the limit of large block length differs
      from the one in the fixed-length and asymptotically faithful scenario. The amount
      of this gap is interpreted as the genuinely quantum part being incompressible in
      the former scenario.

PMID- 12190443
TI  - Hiding classical data in multipartite quantum states.
AB  - We present a general technique for hiding a classical bit in multipartite quantum
      states. The hidden bit, encoded in the choice of one of two possible density
      operators, cannot be recovered by local operations and classical communication
      without quantum communication. The scheme remains secure if quantum communication
      is allowed between certain partners, and can be designed for any choice of
      quantum communication patterns to be secure, but to allow near perfect recovery
      for all other patterns. No entanglement is needed since the hiding states can be
      chosen to be separable. A single ebit of prior entanglement is not sufficient to
      break the scheme.

PMID- 12190444
TI  - Quantitative study of macroscopic quantum tunneling in a dc SQUID: a system with
      two degrees of freedom.
AB  - To test whether the theory of macroscopic quantum tunneling (MQT) is applicable
      to systems with 2 degrees of freedom, we experimentally investigated the
      switching current distribution of a dc SQUID. Using sample parameters determined
      from measurements at T=4.2 K, we are able to make quantitative comparison to the
      theories from 8 mK to 4.2 K. The excellent agreement between the data and the MQT
      theory demonstrates that tunneling from the zero-voltage state of the dc SQUID is
      well described by the quantum mechanics.

PMID- 12190445
TI  - Nonlinear spin-polarized transport through a ferromagnetic domain wall.
AB  - A domain wall separating two oppositely magnetized regions in a ferromagnetic
      semiconductor exhibits, under appropriate conditions, strongly nonlinear I-V
      characteristics similar to those of a p-n diode. We study these characteristics
      as functions of wall width and temperature. As the width increases or the
      temperature decreases, direct tunneling between the majority spin bands reduces
      the effectiveness of the diode. This has important implications for the zero
      field quenched resistance of magnetic semiconductors and for the design of a
      recently proposed spin transistor.

PMID- 12190446
TI  - Shear-induced stress relaxation in a two-dimensional wet foam.
AB  - We report on experimental measurements of the flow behavior of a wet, two
      dimensional foam under conditions of slow, steady shear. The initial response of
      the foam is elastic. Above the yield strain, the foam begins to flow. The flow
      consists of irregular intervals of elastic stretch followed by sudden reductions
      of the stress, i.e., stress drops. We report on the distribution of the stress
      drops as a function of the applied shear rate. We also comment on our results in
      the context of various two-dimensional models of foams.

PMID- 12190447
TI  - Option pricing formulas based on a non-Gaussian stock price model.
AB  - Options are financial instruments that depend on the underlying stock. We explain
      their non-Gaussian fluctuations using the nonextensive thermodynamics parameter
      q. A generalized form of the Black-Scholes (BS) partial differential equation and
      some closed-form solutions are obtained. The standard BS equation (q=1) which is
      used by economists to calculate option prices requires multiple values of the
      stock volatility (known as the volatility smile). Using q=1.5 which well models
      the empirical distribution of returns, we get a good description of option prices
      using a single volatility.

PMID- 12190448
TI  - Quantum Zeno subspaces.
AB  - The quantum Zeno effect is recast in terms of an adiabatic theorem when the
      measurement is described as the dynamical coupling to another quantum system that
      plays the role of apparatus. A few significant examples are proposed and their
      practical relevance discussed. We also focus on decoherence-free subspaces.

PMID- 12190449
TI  - Greenberger-Horne-Zeilinger paradoxes for many qudits.
AB  - We construct Greenberger-Horne-Zeilinger (GHZ) contradictions for three or more
      parties sharing an entangled state, the dimension of each subsystem being an even
      integer d. The simplest example that goes beyond the standard GHZ paradox (three
      qubits) involves five ququats (d=4). We then examine the criteria that a GHZ
      paradox must satisfy in order to be genuinely M partite and d dimensional.

PMID- 12190450
TI  - Lee-Yang zeros and phase transitions in nonequilibrium steady states.
AB  - We consider how the Lee-Yang description of phase transitions in terms of
      partition function zeros applies to nonequilibrium systems. Here, one does not
      have a partition function; instead we consider the zeros of a steady-state
      normalization factor in the complex plane of the transition rates. We obtain the
      exact distribution of zeros in the thermodynamic limit for a specific model, the
      boundary-driven asymmetric simple exclusion process. We show that the
      distributions of zeros at the first- and the second-order nonequilibrium phase
      transitions of this model follow the patterns known in the Lee-Yang equilibrium
      theory.

PMID- 12190451
TI  - Method of Gaussian equivalent representation: a new technique for reducing the
      sign problem of functional integral methods.
AB  - We report on the specific features of the sign problem in the classical auxiliary
      field methodology and the strategies employed for its alleviation. In particular,
      we focus on a new technique based on the method of Gaussian equivalent
      representation of Efimov and Nogovitsin [Physica (Amsterdam) 234A, 506 (1996)]]
      with which we could ameliorate the convergence properties significantly. We
      believe that this technique can also provide an interesting possibility to reduce
      the sign problem of other methods of computer simulation based on a functional
      integral approach.

PMID- 12190452
TI  - Zurek-Kibble domain structures: the dynamics of spontaneous vortex formation in
      annular Josephson tunnel junctions.
AB  - Phase transitions create a domain structure with defects, which has been argued
      by Zurek and Kibble (ZK) to depend in a characteristic way on the quench rate. We
      present an experiment to measure the ZK scaling exponent sigma. Using long
      symmetric Josephson tunnel junctions, for which the predicted index is
      sigma=0.25, we find sigma=0.27+/-0.05. Further, we agree with the ZK prediction
      for the overall normalization.

PMID- 12190453
TI  - Holography stabilizes the vacuum energy.
AB  - Gravitational holography is argued to render the cosmological constant stable
      against divergent quantum corrections, thus providing a technically natural
      solution to the cosmological constant problem. Evidence for quantum stability of
      the cosmological constant is illustrated in a number of examples including bulk
      descriptions in terms of delocalized degrees of freedom, boundary screen
      descriptions on stretched horizons, and nonsupersymmetric conformal field
      theories as dual descriptions of anti-de Sitter space. In an expanding universe,
      holographic quantum contributions to the stress-energy tensor are argued to be at
      most of order the energy density of the dominant matter component.

PMID- 12190454
TI  - Small cosmological constant from the QCD trace anomaly?
AB  - According to recent astrophysical observations the large scale mean pressure of
      our present Universe is negative suggesting a positive cosmological constant-like
      term. The issue of whether nonperturbative effects of self-interacting quantum
      fields in curved space-times may yield a significant contribution is addressed.
      Focusing on the trace anomaly of quantum chromodynamics, a preliminary estimate
      of the expected order of magnitude yields a remarkable coincidence with the
      empirical data, indicating the potential relevance of this effect.

PMID- 12190456
TI  - Diffractive Higgs boson production at the Fermilab Tevatron and the CERN Large
      Hadron Collider.
AB  - Improved possibilities to find the Higgs boson in diffractive events, having less
      hadronic activity, depend on whether the cross section is large enough. Based on
      the soft color interaction models that successfully describe diffractive hard
      scattering at DESY HERA and the Fermilab Tevatron, we find that only a few
      diffractive Higgs events may be produced at the Tevatron, but we predict a
      substantial rate at the CERN Large Hadron Collider.

PMID- 12190455
TI  - Runaway dilaton and equivalence principle violations.
AB  - In a recently proposed scenario, where the dilaton decouples while cosmologically
      attracted towards infinite bare string coupling, its residual interactions can be
      related to the amplitude of density fluctuations generated during inflation, and
      are large enough to be detectable through a modest improvement on present tests
      of free-fall universality. Provided it has significant couplings to either dark
      matter or dark energy, a runaway dilaton can also induce time variations of the
      natural "constants" within the reach of near-future experiments.

PMID- 12190457
TI  - Nuclear-polarization correction to the bound-electron g factor in heavy
      hydrogenlike ions.
AB  - The influence of nuclear polarization on the bound-electron g factor in heavy
      hydrogenlike ions is investigated. Numerical calculations are performed for the K
      and L-shell electrons taking into account the dominant virtual nuclear
      excitations. This determines the ultimate limit for tests of QED utilizing
      measurements of the bound-electron g factor in highly charged ions.

PMID- 12190460
TI  - Laser spectroscopy of cooled zirconium fission fragments.
AB  - The first on-line laser spectroscopy of cooled fission fragments is reported. The
      r ions, produced in uranium fission, were extracted and separated using an ion
      guide isotope separator. The ions were cooled and bunched for collinear laser
      spectroscopy by a gas-filled linear Paul trap. New results for nuclear mean
      square charge radii, dipole, and quadrupole moments are reported across the N=60
      shape change. The mean-square charge radii are found to be almost identical to
      those of the Sr isotones and previously offered modeling of the radial changes is
      critically reviewed.

PMID- 12190461
TI  - Isomer-resolved ion spectroscopy.
AB  - We demonstrate the isomer-resolved spectroscopy of gas-phase ions, with different
      geometries separated prior to spectroscopic probe using ion mobility techniques.
      Specifically, ring and chain isomers of carbon cluster anions with 10;-12 atoms
      have been separated by ion mobility/mass spectrometry and examined by
      photoelectron spectroscopy. This methodology should also apply to other ion
      spectroscopies, including IR photodissociation.

PMID- 12190458
TI  - Improved measurement of /V(cb)/ using B-->D*l nu decays.
AB  - We determine the weak coupling /V(cb)/ between the b and c quarks using a sample
      of 3 x 10(6) BB; events in the CLEO detector at the Cornell Electron Storage
      Ring. We determine the yield of reconstructed B-->D*l nu; decays as a function of
      w, the boost of the D* in the B rest frame, and from this we obtain the
      differential decay rate d Gamma/dw. By extrapolating d Gamma/dw to w=1, the
      kinematic end point at which the D* is at rest relative to the B, we extract the
      product /V(cb)/F(1), where F(1) is the form factor at w=1. Combined with
      theoretical results for F(1) we determine /V(cb)/=0.0469+/-0.0014(stat)+/
      0.0020(syst)+/-0.0018(theor).

PMID- 12190462
TI  - Clear experimental evidence for p-wave attachment-threshold behavior in electron
      attachment to chlorine molecules.
AB  - Using the laser photoelectron attachment method and chlorine molecules in a
      seeded supersonic beam, we have measured the energy dependence of the cross
      section for dissociative electron attachment (DA; Cl- formation) over the range 0
      195 meV with an energy width of about 1 meV. Our data provide the first clear
      experimental evidence for p-wave behavior of a DA cross section near zero energy
      and are in good overall agreement with recent theoretical predictions.

PMID- 12190463
TI  - Radiative recombination enhancement of bare ions in storage rings with electron
      cooling.
AB  - Experiments on ion-electron recombination in electron coolers show an enhancement
      of the recombination rate with respect to the standard theory. The theoretical
      explanation of this effect is an active field of research. Here a parameter-free
      model is presented in terms of the Vlasov equation. Its inherent scaling rests on
      two dimensionless variables and agrees with measurements. Additionally, numerical
      calculations yield the correct magnitude for the enhancement and trace its cause
      to the process of beam merging.

PMID- 12190464
TI  - Symmetry-breaking instability of multimode vector solitons.
AB  - We show experimentally that the two-component multimode spatial optical vector
      soliton, i.e., a two-hump self-guided laser beam, exhibits in Kerr media a sharp
      space-inversion symmetry-breaking instability. The experiment is performed in a
      CS2 planar waveguide using the orthogonal circular polarization states of light
      as the two components of the vector soliton.

PMID- 12190465
TI  - Field quantization for chaotic resonators with overlapping modes.
AB  - Feshbach's projector technique is employed to quantize the electromagnetic field
      in optical resonators with an arbitrary number of escape channels. We find
      spectrally overlapping resonator modes coupled due to the damping and noise
      inflicted by the external radiation field. For wave chaotic resonators the mode
      dynamics is determined by a non-Hermitean random matrix. Upon including an
      amplifying medium, our dynamics of open-resonator modes may serve as a starting
      point for a quantum theory of random lasing.

PMID- 12190466
TI  - Modal interference and dynamical instability in a solid-state slice laser with
      asymmetric end-pumping.
AB  - We observed complicated emission patterns consisting of different transverse
      modes and associated intensity pulsations at beat frequencies between pairs of
      transverse eigenmodes in a solid-state thin-slice Fabry-Perot laser with
      asymmetric end-pumping. The dependence of transverse patterns and pulsation
      frequencies on pump power has been demonstrated. The interference among
      nonorthogonal transverse eigenmodes, which are formed in a deformed Fabry-Perot
      microcavity possessing an asymmetric, gradient refractive-index potential for
      optical waves, is proposed for explaining observed instabilities. Intensity
      modulations have been remarkably reproduced by numerical simulations of model
      equations.

PMID- 12190467
TI  - Stable quantum resonances in atom optics.
AB  - A theory for stabilization of quantum resonances by a mechanism similar to one
      leading to classical resonances in nonlinear systems is presented. It explains
      recent surprising experimental results, obtained for cold cesium atoms when
      driven in the presence of gravity, and leads to further predictions. The theory
      makes use of invariance properties of the system allowing for separation into
      independent kicked rotor problems. The analysis relies on a fictitious classical
      limit where the small parameter is not Planck's constant, but rather the detuning
      from the frequency that is resonant in the absence of gravity.

PMID- 12190468
TI  - Forcing and velocity correlations in a vibrated granular monolayer.
AB  - The role of forcing on the dynamics of a vertically shaken granular monolayer is
      investigated. Using a flat plate, surprising negative velocity correlations are
      measured. A mechanism for this anticorrelation is proposed with support from both
      experimental results and molecular dynamics simulations. Using a rough plate,
      velocity correlations are positive, and the velocity distribution evolves from a
      Gaussian at very low densities to a broader distribution at high densities. These
      results are interpreted as a balance between stochastic forcing, interparticle
      collisions, and friction with the plate.

PMID- 12190470
TI  - Period-doubling bifurcations from breaking the spherical symmetry in
      sonoluminescence: experimental verification.
AB  - Using a fiber-based four-channel correlation scheme to investigate spatial and
      temporal correlations, we show that observations of period-doubling phenomena in
      single bubble sonoluminescence are primarily a result of spontaneously breaking
      the spherical symmetry in the bubble collapse and, at most, may show up as
      secondary effects in the flash-to-flash spatially integrated light output.

PMID- 12190469
TI  - Force chains, microelasticity, and macroelasticity.
AB  - It has been claimed that quasistatic granular materials, as well as nanoscale
      materials, exhibit departures from elasticity even at small loadings. It is
      demonstrated, using 2D and 3D models with interparticle harmonic interactions,
      that such departures are expected at small scales [below O(100) particle
      diameters], at which continuum elasticity is invalid, and vanish at large scales.
      The models exhibit force chains on small scales, and force and stress
      distributions which agree with experimental findings. Effects of anisotropy,
      disorder, and boundary conditions are discussed as well.

PMID- 12190459
TI  - Net charge fluctuations in Au + Au interactions at sqrt[s(NN)]=130 GeV.
AB  - Data from Au + Au interactions at sqrt[s(NN)]=130 GeV, obtained with the PHENIX
      detector at the Relativistic Heavy-Ion Collider, are used to investigate local
      net charge fluctuations among particles produced near midrapidity. According to
      recent suggestions, such fluctuations may carry information from the quark-gluon
      plasma. This analysis shows that the fluctuations are dominated by a stochastic
      distribution of particles, but are also sensitive to other effects, like global
      charge conservation and resonance decays.

PMID- 12190471
TI  - Broken symmetries and pattern formation in two-frequency forced faraday waves.
AB  - We exploit the approximate (broken) symmetries of time translation, time
      reversal, and Hamiltonian structure to obtain general scaling laws governing the
      process of pattern formation in weakly damped Faraday waves. Using explicit
      parameter symmetries we determine, for the case of two-frequency forcing, how the
      strength of observed three-wave interactions depends on the frequency ratio and
      on the relative phase of the two driving terms. These symmetry-based predictions
      are verified for numerically calculated coefficients, and help explain the
      results of recent experiments.

PMID- 12190472
TI  - Dynamics of liquid nanojets.
AB  - We study the breakup of a liquid jet a few nanometers in diameter, based on a
      stochastic differential equation derived recently by Moseler and Landman [Science
      289, 1165 (2000)]. In agreement with their simulations, we confirm that noise
      qualitatively changes the characteristics of breakup, leading to symmetric
      profiles. Using the path integral description, we find a self-similar profile
      that describes the most probable breakup mode. As illustrated by a simple
      physical argument, noise is the driving force behind pinching, speeding up the
      breakup to make surface tension irrelevant.

PMID- 12190473
TI  - Shape oscillations and stability of charged microdroplets.
AB  - Classical Rayleigh theory predicts an instability of a surface charged liquid
      sphere, when the Coulomb energy E(C) exceeds twice the surface energy E(S).
      Previously, electrified liquid droplets have been found to disintegrate at a
      fissility X=E(C)/2E(S) well below one, however. We determine the stability of
      charged droplets in an electrodynamic levitator by observing the amplitude and
      phase of their quadrupolar shape oscillations as a function of the fissility.
      With this novel approach, which does not rely on an independent determination of
      the charge and surface tension of the droplets, we are able to confirm for the
      first time the Rayleigh limit of stability at X=1 for micrometer sized droplets
      of ethylene glycol.

PMID- 12190474
TI  - Experimental investigation of the three-dimensional interaction of a strong shock
      with a spherical density inhomogeneity.
AB  - Laser-driven experiments are described which probe the interaction of a very
      strong shock with a spherical density inhomogeneity. The interaction is viewed
      from two orthogonal directions enabling visualization of both the initial
      distortion of the sphere into a double vortex ring structure as well as the onset
      of an azimuthal instability that ultimately results in the three-dimensional
      breakup of the ring. The experimental results are compared with 3D numerical
      simulations and are shown to be in remarkable agreement with the incompressible
      theory of Widnall et al. [J. Fluid Mech. 66, 35 (1974)].

PMID- 12190475
TI  - MeV ion jets from short-pulse-laser interaction with thin foils.
AB  - Collimated jets of carbon and fluorine ions up to 5 MeV/nucleon ( approximately
      100 MeV) are observed from the rear surface of thin foils irradiated with laser
      intensities of up to 5 x 10 (19)W/cm(2). The normally dominant proton
      acceleration could be surpressed by removing the hydrocarbon contaminants by
      resistive heating. This inhibits screening effects and permits effective energy
      transfer and acceleration of other ion species. The acceleration dynamics and the
      spatiotemporal distributions of the accelerating E fields at the rear surface of
      the target are inferred from the detailed spectra.

PMID- 12190476
TI  - Shell mix in the compressed core of spherical implosions.
AB  - The Rayleigh-Taylor instability in its highly nonlinear, turbulent stage causes
      atomic-scale mixing of the shell material with the fuel in the compressed core of
      inertial-confinement fusion targets. The density of shell material mixed into the
      outer core of direct-drive plastic-shell spherical-target implosions on the 60
      beam, OMEGA laser system is estimated to be 3.4(+/-1.2) g/cm(3) from time
      resolved x-ray spectroscopy, charged-particle spectroscopy, and core x-ray
      images. The estimated fuel density, 3.6(+/-1) g/cm(3), accounts for only
      approximately 50% of the neutron-burn-averaged electron density, n(e)=2.2(+/
      0.4)x10(24) cm(-3).

PMID- 12190477
TI  - Experiments and molecular-dynamics simulation of elastic waves in a plasma
      crystal radiated from a small dipole source.
AB  - The radiation of elastic waves from a localized source is observed experimentally
      in a two-dimensional plasma crystal. An initial shear stress applied by a laser
      forms a small dipole source. The emerging complex wave pattern is shown to
      consist of outgoing compressional and shear wave pulses. Subsequent structures
      are identified as inward-going waves due to the finite size of the source region,
      which reappear on the opposite side. The compressional wave forms a trailing wave
      train due to strong dispersion, while the nondispersive shear wave evolves into a
      vortex-antivortex pair on either side. The experiments are compared with a
      molecular-dynamics simulation.

PMID- 12190478
TI  - Structure of water adsorbed on a mica surface.
AB  - Monte Carlo simulations of hydration water on the mica (001) surface under
      ambient conditions revealed water molecules bound closely to the ditrigonal
      cavities in the surface, with a lateral distribution of approximately one per
      cavity, and water molecules (interposed between K+ counter ions) in a layer
      situated about 2.5 A from a surface O along a direction normal to the (001)
      plane. The calculated water O density profile was in quantitative agreement with
      recent x-ray reflectivity measurements indicating strong lateral ordering of the
      hydration water but liquidlike disorder otherwise.

PMID- 12190479
TI  - Chevron defect at the intersection of grain boundaries with free surfaces in Au.
AB  - We have identified a new defect at the intersection between grain boundaries and
      surfaces in Au using atomic resolution transmission electron microscopy. At the
      junction line of 90 degrees <110> tilt grain boundaries of (110)-(001)
      orientation with the free surface, a small segment of the grain boundary, about 1
      nm in length, dissociates into a triangular region with a chevronlike stacking
      disorder and a distorted hcp structure. The structure and stability of these
      defects are confirmed by atomistic simulations, and we point out the relationship
      with the one-dimensional incommensurate structure of the grain boundary.

PMID- 12190480
TI  - Molecular dynamics simulation of brittle fracture in silicon.
AB  - Brittle fracture in silicon is simulated with molecular dynamics utilizing a
      modified embedded atom method potential. The simulations produce propagating
      crack speeds that are in agreement with previous experimental results over a
      large range of fracture energy. The dynamic fracture toughness is found to be
      equal to the energy consumed by creating surfaces and lattice defects in
      agreement with theoretical predictions. The dynamic fracture toughness is
      approximately 1/3 of the static strain energy release rate, which results in a
      limiting crack speed of 2/3 of the Rayleigh wave speed.

PMID- 12190481
TI  - Dynamic heterogeneities in a simple liquid over different time scales.
AB  - The heterogeneous features of the supercooled state over different time regimes
      are explored in a self-consistent mode-coupling mode. The exponent a for the mean
      square displacement <r(2)(t)> approximately t(a), of a tagged particle is
      computed. The non-Gaussian parameter alpha(2)(t) shows a peak in the short time
      regime in addition to a second peak over longer times. The position of the short
      time peak in alpha(2)(t) hardly shifts, while that of the other grows with
      density.

PMID- 12190482
TI  - General sum rule for chiral index of coalescing ultrathin nanotubes.
AB  - We investigated the coalescence of ultrathin carbon nanotubes (UTCNTs) using the
      tight-binding molecular dynamics simulation technique. We have found that two
      UTCNTs having the same or different chirality can coalesce without initially
      introducing atomic defects to enhance the reaction. The chiral index of the
      coalesced nanotube was found to be given as a vector sum of the indices of the
      original nanotubes, which can be explained geometrically in terms of the
      developments of the nanotubes. The results clearly show that the chirality can be
      changed through chemical reaction, which might suggest a possibility of chirality
      control.

PMID- 12190483
TI  - Self-diffusion of (31)Si and (71)Ge in relaxed Si(0.20)Ge(0.80) layers.
AB  - Self-diffusion of implanted (31)Si and (71)Ge in relaxed Si(0.20)Ge(0.80) layers
      has been studied in the temperature range 730-950 degrees C by means of a
      modified radiotracer technique. The temperature dependences of the diffusion
      coefficients were found to be Arrhenius-type with activation enthalpies of 3.6 eV
      and 3.5 eV and preexponential factors of 7.5 x 10(-3) m(2) s(-1) and 8.1 x 10(-3)
      m(2) s(-1) for (31)Si and (71)Ge , respectively. These results suggest that, as
      in Ge, in Si(0.20)Ge(0.80) both (31)Si and (71)Ge diffuse via a vacancy
      mechanism. Since in Si(0.20)Ge(0.80) (71)Ge diffuses only slightly faster than
      (31)Si , in self-diffusion studies on Si-Ge (71)Ge radioisotopes may be used as
      substitutes for the "uncomfortably" short-lived (31)Si radiotracer atoms.

PMID- 12190484
TI  - Translational heating of D(2) molecules thermally desorbed from Si(100) and
      Ge(100) surfaces.
AB  - The translational energies of D(2) molecules thermally desorbed from the Si(100)
      and Ge(100) surfaces under a heating rate of 6 K/s have been measured. In
      contrast to the previous laser desorption study, results show a considerable
      translational heating; the observed translational temperature is about 3 times
      higher than the desorption temperature for both surfaces. This fact indicates
      that energy barriers for adsorption are present even in the desorption pathway.
      Detailed balance is applicable to the adsorption and desorption dynamics of
      hydrogen on the Si(100) surface.

PMID- 12190485
TI  - Microscopic dynamics of silicon oxidation.
AB  - We study the silicon oxidation process and the dynamic structure of the SiO2-Si
      (001) interface using a grand canonical Monte Carlo approach. We find that Si-O
      Si bridge bonds are the main building blocks of the advancing interface, and we
      identify a kinetic pathway that continually creates new bridge bonds. Oxidation
      proceeds by local events, with little evidence of "step flow" in the simulation.
      Yet the interface remains remarkably smooth and abrupt as it advances.

PMID- 12190486
TI  - Theory of ferromagnetism in doped excitonic condensates.
AB  - Nesting in a semimetal can lead to an excitonic-insulator state with spontaneous
      coherence between conduction and valence bands and a gap for charged excitations.
      We present a theory of the ferromagnetic state that occurs when the density of
      electrons in the conduction band and holes in the valence band differ. We find an
      unexpectedly rich doping-field phase diagram and an unusual collective excitation
      spectrum that includes two gapless collective modes. We predict regions of doping
      and external field in which phase-separated condensates of electrons and holes
      with parallel spins and opposing spins coexist.

PMID- 12190487
TI  - Spectroscopy of the electron-electron interaction in solids.
AB  - The spectrum of a photoexcited electron pair carries detailed information on the
      electron-electron interaction in metals. This is deduced from the results of a
      theoretical model presented here for the treatment of the double-photoelectron
      emission from surfaces. Main features in the two-particle spectra are assigned to
      (a) the exchange-correlation interaction, (b) the electronic band structure, (c)
      the photoelectron diffraction, and (d) the specific experimental setup.
      Comparison with experiments is made and common features and differences to the
      atomic case are pointed out.

PMID- 12190488
TI  - Effects of hydrogen on the electronic properties of dilute GaAsN alloys.
AB  - Nitrogen has profound effects on the electronic structure of GaAs, as only a few
      percent of N can drastically lower the band gap. It is, however, not recognized
      that the same amount of N can also qualitatively alter the electronic behavior of
      hydrogen: First-principles calculations reveal that, in GaAsN, a H atom bonds to
      N and can act as a donor in its own right, whereas in GaAs and GaN, H is
      amphoteric, causing passivation instead. At high Fermi energy and H
      concentration, a N complex with two H was found to have lower energy than the
      single-H configuration. By removing the effect of N, this electrically inactive
      complex restores the gap of GaAs.

PMID- 12190489
TI  - Three-dimensional fermi-liquid ground state in the quasi-one-dimensional cuprate
      PrBa(2)Cu(4)O(8).
AB  - The interchain resistivity of PrBa(2)Cu(4)O(8) has been measured in high magnetic
      fields up to 30 T. Co-herent interchain transport at low temperatures is
      destroyed by a large magnetic field applied perpendicular to the CuO chains.
      Comparisons with quasiclassical transport theory provide strong experimental
      support for a three-dimensional Fermi-liquid ground state in PrBa(2)Cu(4)O(8),
      despite extreme anisotropy in its electronic properties and the presence of
      strong electron correlations.

PMID- 12190490
TI  - Size-dependent tunneling and optical spectroscopy of CdSe quantum rods.
AB  - Photoluminescence excitation spectroscopy and scanning-tunneling spectroscopy are
      used to study the electronic states in CdSe quantum rods that manifest a
      transition from a zero-dimensional to a one-dimensional quantum-confined
      structure. Both optical and tunneling spectra show that the level structure
      depends primarily on the diameter of the rod and not its length. With increasing
      diameter, the band gap and the excited state level spacings shift to the red. The
      level structure was assigned using a multiband effective-mass model, showing a
      similar dependence on rod dimensions.

PMID- 12190491
TI  - Metal-molecule contacts and charge transport across monomolecular layers:
      measurement and theory.
AB  - Charge transport studies across molecular length scales under symmetric and
      asymmetric metal-molecule contact conditions using a simple crossed-wire tunnel
      junction technique are presented. It is demonstrated that oligo(phenylene
      ethynylene), a conjugated organic molecule, acts like a molecular wire under
      symmetric contact conditions, but exhibits characteristics of a molecular diode
      when the connections are asymmetric. To understand this behavior, we have
      calculated current-voltage (I-V) characteristics using extended Huckel theory
      coupled with a Green's function approach. The experimentally observed I-V
      characteristics are in excellent qualitative agreement with the theory.

PMID- 12190492
TI  - Competing phases in the high field phase diagram of (TMTSF)(2)ClO(4).
AB  - A model is presented for the high field phase diagram of (TMTSF)(2)ClO(4), taking
      into account the anion ordering, which splits the Fermi surface into two bands.
      For strong enough field, the largest metal spin density wave critical temperature
      corresponds to the N=0 phase, which originates from two intraband nesting
      processes. At lower temperature, the competition between these processes puts at
      disadvantage the N=0 phase vs the N=1 phase, which is due to interband nesting. A
      first order transition then takes place from the N=0 to N=1 phase. We ascribe to
      this effect the experimentally observed phase diagrams.

PMID- 12190493
TI  - Atomic scale imaging and spectroscopy of a CuO(2) plane at the surface of
      Bi(2)Sr(2)CaCu(2)O(8+delta).
AB  - We have used a scanning tunneling microscope to demonstrate that a single CuO2
      plane can form a stable and atomically ordered layer at the surface of
      Bi(2)Sr(2)CaCu(2)O(8+delta). In contrast to previous studies on high-T(c)
      surfaces, the CuO2-terminated surface exhibits a strongly suppressed tunneling
      conductance at low voltages. We consider a number of different explanations for
      this phenomena and propose that it may be caused by how the orbital symmetry of
      the CuO2 plane's electronic states affects the tunneling process.

PMID- 12190495
TI  - Pressure-induced transition from localized electron toward band
      antiferromagnetism in LaMnO(3).
AB  - The temperature dependence of the ac susceptibility under pressure has been used
      to track the Neel temperature T(N) of the Mott insulators LaMnO3, CaMnO3, and
      YCrO3. Bloch's rule relating T(N) to volume V, viz., alpha=dlog(T(N)/dlog(V=-3.3,
      is obeyed in YCrO3 and CaMnO3; it fails in LaMnO3. This breakdown is interpreted
      to be due to a sharp increase in the factor [U(-1)+(2Delta)(-1)] entering the
      superexchange perturbation formula. A first-order change at 7 kbar indicates that
      the transition from localized-electron to band magnetism is not smooth.

PMID- 12190494
TI  - Oxygen isotope effect in the ab-plane reflectance of underdoped YBa(2)Cu(3)O(7
      delta).
AB  - We have measured the effect of oxygen isotope substitution on the ab-plane
      reflectance of underdoped YBa(2)Cu(3)O(7-delta). The frequency shift of the
      transverse optic phonons due to the substitution of 16O by 18O yields an isotope
      effect of the expected magnitude for copper-oxygen stretching modes with
      alpha=0.5+/-0.1. The reflectance shoulder at 400-500 cm(-1) shows a much smaller
      exponent of alpha=0.1+/-0.1 in the normal state and alpha=0.23+/-0.1 in the
      superconducting state. These observations suggest that the shoulder is of
      electronic origin and not due to a phonon mode as has been suggested recently.

PMID- 12190496
TI  - Anomalous spin-density distribution on oxygen and Ru in Ca(1.5)Sr(0.5)RuO(4):
      polarized neutron diffraction study.
AB  - By means of polarized neutron diffraction in a magnetic field of 7.0 T at 1.6 K
      an anomalously large magnetization density is observed on the in-plane oxygen in
      Ca(1.5)Sr(0.5)RuO(4). Field-induced moments of different ions are determined by
      refinement on the flipping ratios, yielding micro(Ru)=0.346(11)micro(B),
      micro(O1)=0.076(6)micro(B), and micro(O2)=0.009(6)micro(B). The moment on the
      oxygen arises from the strong hybridization between the Ru-4d and O-2p orbitals.
      The maximum entropy magnetization density reconstruction reveals a strongly
      anisotropic density at the Ru site, consistent with the distribution of the xy
      (t(2g) band) d orbitals.

PMID- 12190497
TI  - New possibilities for tuning ultrathin cobalt film magnetic properties by a noble
      metal overlayer.
AB  - Complementary multiscale magneto-optical studies based on the polar Kerr effect
      are carried out on an ultrathin cobalt wedge covered with a silver wedge and
      subsequently with the Au thick layer. A few monolayers of Ag are found to have a
      substantial effect on magnetic anisotropy, the coercivity field, and Kerr
      rotation. The silver overlayer thickness-driven magnetic reorientation from easy
      axis to easy plane generates a new type of 90 degrees magnetic wall for cobalt
      thicknesses between 1.3 and 1.8 nm. The tuning of the wall width in a wide range
      is possible. Tailoring of the overlayer structure can be used for ultrathin film
      magnetic patterning.

PMID- 12190498
TI  - Melting-induced enhancement of the second-harmonic generation from metal
      nanoparticles.
AB  - We report on the generation of second-harmonic signals by irradiating monolayers
      of high purity Ga nanoparticles, embedded in a SiOx matrix, with femtosecond
      laser pulses at 800 nm. A remarkable melting-induced enhancement of the second
      harmonic generation is observed in correspondence of the phase transition. In
      addition, the hysteresis cycle of nonlinear transmittance is shown to be
      amplified a factor of 80-100 with respect to the linear response and interpreted
      in the framework of a nonlinear effective-medium model.

PMID- 12190499
TI  - Layered perovskites with giant spontaneous polarizations for nonvolatile
      memories.
AB  - A series of titanate-based layered perovskites having large values of the
      spontaneous polarization P(s) were developed for their applcations to nonvolatile
      ferroelectric random access memories. Among these, the Nd-modified bismuth
      titanate [Bi(4-x)Nd(x)Ti(3)O(12) (BNdT)] system exhibited the most remarkable
      ferroelectric properties. The c-axis oriented BNdT capacitor was characterized by
      a switchable remanent polarization 2P(r) of over 100 microC/cm(2) and imprinting
      and fatigue-free behavior. The active Ti site responsible for the giant P(s) was
      identified with the help of Rietveld analysis, x-ray absorption near-edge
      structure study, and ab initio quantum computations.

PMID- 12190500
TI  - Field distribution and flux-line depinning in MgB (2).
AB  - We report the first observation of the field distribution and flux-line lattice
      (FLL) depinning in the vortex-state (VS) of a type-II superconductor probed by
      conduction electron spin resonance (CESR). CESR was performed in MgB (2) (T(c)
      approximately 39 K) at 4.1 GHz (1455 Oe) and 9.5 GHz (3390 Oe). The field
      distribution, n(H), and a standard deviation of sigma approximately 14 Oe (at 28
      K/4.1 GHz and at 7 K/9.5 GHz) were inferred, respectively, from the distortion
      and broadening of the CESR in the VS. For both frequencies, the FLL depinning
      temperature was determined.

PMID- 12190501
TI  - Bloch waves, periodic feature maps, and cortical pattern formation.
AB  - Perturbation methods are used to solve the eigenvalue problem for cortical
      pattern formation in the presence of long-range neural connections. Such
      connections have a crystallinelike structure that breaks Euclidean symmetry to
      the discrete symmetry of a planar lattice group. Conditions for marginal
      stability are derived with the associated eigenmodes identified as Bloch waves.

PMID- 12190502
TI  - Diffusion, peer pressure, and tailed distributions.
AB  - We present a general, physically motivated nonlinear and nonlocal advection
      equation in which the diffusion of interacting random walkers competes with a
      local drift arising from a kind of peer pressure. We show, using a mapping to an
      integrable dynamical system, that on varying a parameter the steady-state
      behavior undergoes a transition from the standard diffusive behavior to a
      localized stationary state characterized by a tailed distribution. Finally, we
      show that recent empirical laws on economic growth can be explained as a
      collective phenomenon due to peer pressure interaction.

PMID- 12190503
TI  - Microscopics of complexation between long DNA molecules and positively charged
      colloids.
AB  - Extensive atomic force and electron microscopy reveal a new, generic DNA-colloid
      complex with a fixed number of DNA bases per colloid. The fiber shaped complex is
      stable in the presence of excess colloids in the solution. As more DNA is added
      to the solution and the ratio between colloids and DNA approaches the fiber's
      stoichiometry, the system undergoes a sharp coagulation transition. The system is
      restabilized at even higher DNA concentrations through localization of small
      colloid clusters on extensive DNA networks.

PMID- 12190504
TI  - Entropic torque.
AB  - Quantitative predictions are presented of a depletion-induced torque and force
      acting on a single colloidal hard rod immersed in a solvent of hard spheres close
      to a planar hard wall. This torque and force, which are entirely of entropic
      origin, may play an important role for the key-lock principle, according to which
      a biological macromolecule (the key) is functional only in a particular
      orientation with respect to a cavity (the lock).

PMID- 12190505
TI  - Turbulent drag reduction and degradation of DNA.
AB  - Turbulent drag reduction induced by lambda-DNA is studied. The double-stranded
      DNA is found to be a good drag reducer when compared with the other normal linear
      polymers. However, this drag reducing power disappears when the DNA denatures to
      form two single-strand molecules. Mechanical degradation of DNA is also different
      from that of the normal linear-chain polymers: DNA is always cut in half by the
      turbulence. Our results suggest that the mechanism for turbulent degradation of
      DNA is different from that of the normal flexible long-chain polymers.

PMID- 12190506
TI  - High resolution 3D x-ray diffraction microscopy.
AB  - We have imaged a 2D buried Ni nanostructure at 8 nm resolution using coherent x
      ray diffraction and the oversampling phasing method. By employing a 3D imaging
      reconstruction algorithm, for the first time we have experimentally determined
      the 3D structure of a noncrystalline nanostructured material at 50 nm resolution.
      The 2D and 3D imaging resolution is currently limited by the exposure time and
      the computing power, while the ultimate resolution is limited by the x-ray
      wavelengths. We believe these results pave the way for the development of atomic
      resolution 3D x-ray diffraction microscopy.

PMID- 12190507
TI  - Dynamical or landau instability?

PMID- 12190509
TI  - General exact solution to the problem of the probability density for sums of
      random variables.
AB  - The exact explicit expression for the probability density p(N)(x) for a sum of N
      random, arbitrary correlated summands is obtained. The expression is valid for
      any number N and any distribution of the random summands. Most attention is paid
      to application of the developed approach to the case of independent and
      identically distributed summands. The obtained results reproduce all known exact
      solutions valid for the, so called, stable distributions of the summands. It is
      also shown that if the distribution is not stable, the profile of p(N)(x) may be
      divided into three parts, namely a core (small x), a tail (large x), and a
      crossover from the core to the tail (moderate x). The quantitative description of
      all three parts as well as that for the entire profile is obtained. A number of
      particular examples are considered in detail.

PMID- 12190510
TI  - Quantum tweezer for atoms.
AB  - We propose a quantum tweezer for extracting a desired number of neutral atoms
      from a reservoir. A trapped Bose-Einstein condensate is used as the reservoir,
      taking advantage of its coherent nature, which can guarantee a constant outcome.
      The tweezer is an attractive quantum dot, which may be generated by red-detuned
      laser light. By moving at certain speeds, the dot can extract a desired number of
      atoms from the condensate through Landau-Zener tunneling. The feasibility of our
      quantum tweezer is demonstrated through realistic and extensive model
      calculations.

PMID- 12190511
TI  - Vortex rings and lieb modes in a cylindrical Bose-Einstein condensate.
AB  - We present a calculation of a solitary wave propagating along a cylindrical Bose
      Einstein trap. For sufficiently strong couplings of experimental interest, it is
      found to be a hybrid of a one-dimensional (1D) soliton and a three-dimensional
      vortex ring. The calculated energy-momentum dispersion exhibits characteristics
      similar to those of a mode proposed sometime ago by Lieb within a 1D model, as
      well as some rotonlike features.

PMID- 12190512
TI  - Lieb mode in a quasi-one-dimensional bose-einstein condensate of atoms.
AB  - We calculate the dispersion relation associated with a solitary wave in a quasi
      one-dimensional Bose-Einstein condensate of atoms confined in a harmonic,
      cylindrical trap in the limit of weak and strong interactions. In both cases, the
      dispersion relation is linear for long-wavelength excitations and terminates at
      the point where the group velocity vanishes. We also calculate the dispersion
      relation of sound waves in both limits of weak and strong coupling.

PMID- 12190515
TI  - Microscopic correlation functions for the QCD Dirac operator with chemical
      potential.
AB  - A chiral random matrix model with complex eigenvalues is solved as an effective
      model for QCD with nonvanishing chemical potential. The new correlation functions
      derived from it are conjectured to predict the local fluctuations of complex
      Dirac operator eigenvalues at zero virtuality. The parameter measuring the non
      Hermiticity of the random matrix is related to the chemical potential. In the
      phase with broken chiral symmetry all spectral correlations are calculated for
      finite matrix size N and in the large-N limit at weak and strong non-Hermiticity.
      The derivation uses the orthogonality of the Laguerre polynomials in the complex
      plane.

PMID- 12190514
TI  - Radiative decay width measurements of neutral kaon excitations using the
      primakoff effect.
AB  - We use K(L)'s in the 100-200 GeV energy range to produce 147 candidate events of
      the axial vector pair K1(1270)-K1(1400) in the nuclear Coulomb field of a Pb
      target and determine the radiative widths Gamma(K1(1400)-->K0+gamma)=280.8+/
      23.2(stat)+/-40.4(syst) keV and Gamma(K1(1270)-->K0+gamma)=73.2+/-6.1(stat)+/
      28.3(syst) keV. These first measurements appear to be lower than the quark-model
      predictions. We also place upper limits on the radiative widths for K(*)(1410)
      and K(*)(2)(1430) and find that the latter is vanishingly small in accord with
      SU(3) invariance in the naive quark model.

PMID- 12190517
TI  - Non-Born-Oppenheimer isotope effects on the polarizabilities of H2.
AB  - We present non-Born-Oppenheimer quantum-mechanical calculations of the behavior
      of isolated molecules of the H2 isotopomer series in static electric fields. Some
      conceptual aspects of such calculations are discussed. The values for
      polarizabilities and hyperpolarizabilities of the H2 isotopomers which we present
      are the first ever fully nonadiabatic calculated values of these properties.

PMID- 12190518
TI  - Separation and identification of dominant mechanisms in double photoionization.
AB  - Double photoionization by a single photon is often discussed in terms of two
      contributing mechanisms, knockout (two-step-one) and shakeoff, with the latter
      being a pure quantum effect. It is shown that a quasiclassical description of
      knockout and a simple quantum calculation of shakeoff provides a clear separation
      of the mechanisms and facilitates their calculation considerably. The relevance
      of each mechanism at different photon energies is quantified for helium.
      Photoionization ratios, integral, and singly differential cross sections obtained
      by us are in excellent agreement with benchmark experimental data and recent
      theoretical results.

PMID- 12190516
TI  - Sigma-nucleus potential in A=28.
AB  - We have studied the (pi(-),K+) reaction on a silicon target to investigate the
      sigma-nucleus potential. The inclusive spectrum was measured at a beam momentum
      of 1.2 GeV/c with an energy resolution of 3.3 MeV (FWHM) by employing the
      superconducting kaon spectrometer system. The spectrum was compared with
      theoretical calculations within the framework of the distorted-wave impulse
      approximation, which demonstrates that a strongly repulsive sigma-nucleus
      potential with a nonzero size of the imaginary part reproduces the observed
      spectrum.

PMID- 12190519
TI  - Effects of interchannel coupling in associative detachment: electron spectra for
      H+Cl- and H+Br- collisions.
AB  - We present experimental and theoretical energy spectra of the electrons detached
      in collisions of slow Cl- and Br- ions with atomic hydrogen. Nonlocal resonance
      theory predicts two kinds of features in the spectra: steplike structures
      associated with rovibrational onsets and steep rises associated with interchannel
      coupling, the latter being absent in a calculation using the simpler local
      complex potential theory. Our experimental spectra confirm the presence of both
      types of structures and thus the necessity of including interchannel coupling to
      properly describe the product-state distribution.

PMID- 12190513
TI  - Study of CP-violating asymmetries in B0-->pi(+)pi(-) decays.
AB  - We present a measurement of CP-violating asymmetries in B0-->pi(+)pi(-) decays
      based on a 41.8 fb(-1) data sample collected at the Upsilon(4S) resonance with
      the Belle detector at the KEKB asymmetric-energy e(+)e(-) collider. We fully
      reconstruct one neutral B meson as a B0-->pi(+)pi(-) CP eigenstate and identify
      the flavor of the accompanying B meson from its decay products. From the
      asymmetry in the distribution of the time intervals between the two B meson decay
      points, we obtain the CP-violating asymmetry parameters S(pipi)=-1.21(+0.38)(
      0.27)(stat)+0.16-0.13(syst) and A(pipi)=+0.94(+0.25)(-0.31)(stat)+/-0.09(syst).

PMID- 12190521
TI  - Development of grain avalanches.
AB  - We present a new theoretical approach aimed to describe the dynamical properties
      of avalanches. Starting from simple microscopic considerations, we propose an
      analytical derivation accounting for the avalanche growth as a function of time.
      The solution resembles very closely recent experimental observations. We show in
      particular that the two observed regimes of growth proceed from a singularity in
      the rear front velocity as a function of the slope.

PMID- 12190520
TI  - Giant improvement of time-delayed feedback control by spatio-temporal filtering.
AB  - Control of spatio-temporal chaos by the time-delay autosynchronization method is
      improved by several orders of magnitude. Unstable time periodic patterns are
      efficiently stabilized if one employs filters and couplings which originate from
      the Floquet eigenvalue problem of the unstable orbit. We illustrate our scheme by
      an application to a globally coupled reaction-diffusion model which describes
      charge transport in semiconductor devices.

PMID- 12190522
TI  - Inverse cascade regime in shell models of two-dimensional turbulence.
AB  - We consider shell models that display an inverse energy cascade similar to two
      dimensional turbulence (together with a direct cascade of an enstrophylike
      invariant). Previous attempts to construct such models ended negatively, stating
      that shell models give rise to a "quasiequilibrium" situation with equipartition
      of the energy among the shells. We show analytically that the quasiequilibrium
      state predicts its own disappearance upon changing the model parameters in favor
      of the establishment of an inverse cascade regime with Kolmogorov scaling. The
      latter regime is found where predicted, offering a useful model to study inverse
      cascades.

PMID- 12190523
TI  - Spontaneous formation of a plasma hole in a rotating magnetized plasma: a giant
      burgers vortex in a compressible fluid.
AB  - Spontaneous formation of a cylindrical density cavity, or "plasma hole," has been
      observed in a rotating magnetized plasma. Density of the plasma hole is one-tenth
      of that of ambient plasma and is bounded by a steep transition layer of the order
      of several ion Larmor radii. The flow velocity field associated with the plasma
      hole is experimentally determined, exhibiting a monopole vortical structure. It
      is found that the vorticity distribution is localized near the center of the hole
      and is identified as a Burgers vortex. This is the first experimental observation
      of a Burgers vortex in a plasma.

PMID- 12190524
TI  - Superfluid bose liquid with a suppressed BEC and an intensive pair coherent
      condensate as a model of 4He.
AB  - One introduces a model of the superfluid state of a Bose liquid with repulsion
      between bosons, in which at T=0, along with a weak single-particle Bose-Einstein
      condensate, there exists an intensive pair coherent condensate, analogous to the
      Cooper condensate in a Fermi liquid with attraction between fermions. A closed
      system of nonlinear integral equations for the normal and anomalous self-energy
      parts is solved numerically, and a quasiparticle spectrum is obtained, which is
      in good agreement with the experimental spectrum of elementary excitations in
      superfluid 4He. It is shown that the roton minimum in the spectrum is associated
      with the negative minimum of the Fourier component of the pair interaction
      potential.

PMID- 12190525
TI  - Evidence for magnetic field induced changes of the phase of tunneling states:
      spontaneous echoes in (KBr)(1-x)(KCN)(x) in magnetic fields.
AB  - Recently it was discovered that, in contrast to expectations, the low-temperature
      dielectric properties of some multicomponent glasses depend strongly on magnetic
      fields. The low-temperature dielectric response of these materials is governed by
      atomic tunneling systems. We now have investigated the influence of magnetic
      fields on the coherent properties of atomic tunneling states in a crystalline
      host in two-pulse echo experiments. As in glasses, we observe a very strong
      magnetic field dependence of the echo amplitude. Moreover, for the first time we
      have direct evidence that the magnetic fields change the phase of coherent
      tunneling systems.

PMID- 12190526
TI  - Structure of intercalated Cs in zeolite ITQ-4: an array of metal ions and
      correlated electrons confined in a pseudo-1D nanoporous host.
AB  - The presence of Cs+ ions in the pseudo-1D nanopores of zeolite ITQ-4, Si32O64, is
      confirmed by x-ray diffraction and atomic pair distribution function analysis.
      Inside the nanopores the Cs+ ions are found to assemble in zigzag chains and thus
      form an extended, positively charged sublattice providing charge balance for a
      low-density electron gas also confined to the nanopores.

PMID- 12190527
TI  - Gamma spectra resulting from the annihilation of positrons with electrons in a
      single core level.
AB  - The first gamma spectra associated with the annihilation of positrons with
      individual core levels (Cu 3p and Ag 4p) are presented. The spectra were obtained
      by measuring the energy of gamma rays time coincident with Auger electrons
      emitted as a result of positrons annihilating with a selected core level.
      Relativistic calculations show good agreement with experiment over a limited
      range of momenta. However, statistically significant differences indicate that
      the measurements can provide an impetus to new calculations of many body effects
      in positron-core electrons annihilation.

PMID- 12190528
TI  - Sequence of morphological transitions in two-dimensional pattern growth from
      aqueous ascorbic Acid solutions.
AB  - A sequence of morphological transitions in two-dimensional dehydration patterns
      of aqueous solutions of ascorbic acid is observed with humidity as a control
      parameter. Change in morphology occurs due to humidity induced variation in the
      concentration of the metastable supersaturated solution phase formed after
      initial solvent evaporation. As percent humidity is varied from 40 to 80,
      patterns change from compact circular --> radial --> density modulated radial (a
      new morphology) --> density modulated circular --> density modulated dendritic (a
      new morphology) --> dense branching.

PMID- 12190529
TI  - Molecular junctions by joining single-walled carbon nanotubes.
AB  - Crossing single-walled carbon nanotubes can be joined by electron beam welding to
      form molecular junctions. Stable junctions of various geometries are created in
      situ in a transmission electron microscope. Electron beam exposure at high
      temperatures induces structural defects which promote the joining of tubes via
      cross-linking of dangling bonds. The observations are supported by molecular
      dynamics simulations which show that the creation of vacancies and interstitials
      induces the formation of junctions involving seven- or eight-membered carbon
      rings at the surface between the tubes.

PMID- 12190530
TI  - The role of the nanoscale in surface reactions: CO2 on CdSe.
AB  - Cd-rich CdSe nanocrystals below a critical size, under illumination, catalyze CO2
      fixation, but bulk CdSe surfaces do not. We report first-principles calculations
      in which we determine the roles of faceting, deviations from stoichiometry,
      photoexcitation, and electron confinement, and the specific physics of the
      nanoscale. We further establish that catalysis does not occur at the nanocrystal
      surface; instead, neutral molecules adsorb, desorb negatively charged, and react
      elsewhere. Finally, we predict that n-type doped CdSe nanocrystals would be
      effective catalysts without photoexcitation.

PMID- 12190531
TI  - Icosahedral short-range order in deeply undercooled metallic melts.
AB  - Experimental evidence of icosahedral short-range order in stable and deeply
      undercooled melts of pure metallic elements is obtained using the combination of
      electromagnetic levitation with neutron scattering. This icosahedral short-range
      order is shown to occur in the bulk metallic melt independently of the system
      investigated. It strongly increases with the degree of undercooling.

PMID- 12190533
TI  - Existence of a hexatic phase in porous media.
AB  - Molecular simulations for simple fluids in narrow slit-shaped carbon pores
      exhibit crystal-hexatic and hexatic-liquid transitions that are consistent with
      Kosterlitz-Thouless-Halperin-Nelson-Young theory. The temperature range over
      which the hexatic phase is stable is dramatically widened under confinement.
      Remarkably, the transitions, which are continuous for a single adsorbed layer,
      become weakly first order when the pore can accommodate two molecular layers.
      Nonlinear dielectric effect measurements for CCl4 and aniline in activated carbon
      fibers (pore width 1.4 nm) show divergence at these transitions, confirming the
      hexatic phase.

PMID- 12190532
TI  - How well do we know atomic motions of simple liquids?
AB  - Microscopic motions in molten potassium spanning three frequency decades are
      studied by neutron-scattering techniques. These comprise well-defined density
      oscillations and stochastic particle rearrangements and both are modeled on
      microscopic grounds. While vibratory motions are shown to share characteristics
      with those of their parent crystals, dynamic correlations between a diffusing
      particle and its neighbors can be accounted for only semiquantitatively.

PMID- 12190534
TI  - Line tension behavior of a first-order wetting system.
AB  - Line tension of hexaethylene glycol on a silicon wafer is measured with positive
      values up to +2.5x10(-11) N below a contact angle of 6 degrees and negative
      values down to -2x10(-10) N above 6 degrees, as expected for a first-order
      wetting system. From the measured interface potentials, a semiquantitative model
      function for the overall interface potential is derived as a superposition of a
      constant nonretarded van der Waals interaction with a Hamaker constant of 
      2.6x10(-19) J and an exponentially decaying term, allowing the prediction of a
      finite positive line tension at the wetting transition.

PMID- 12190535
TI  - Strain-driven mesoscopic reconstruction of the As/Ge(111) surface.
AB  - Periodic arrays of large hexagonal tiles (up to 170 A in size) are observed on
      As/Ge(111) surfaces. First-principles total energy calculations combined with
      scanning tunneling microscopy reveal a (5-7-5)-ringed structure for the trenches
      that separate the tiles. We find that trenches form via an exothermic process.
      The calculated equilibrium trench spacing of approximately 104 A agrees with
      experiment. Comparison between first-principles calculations and continuum
      elasticity theory suggests that the observed mesoscopic reconstruction is driven
      entirely by long-range surface strain relaxation.

PMID- 12190536
TI  - Robustness of the Van Hove scenario for high-T(c) superconductors.
AB  - The pinning of the Fermi level to the Van Hove singularity and the formation of
      flat bands in the two-dimensional t-t' Hubbard model is investigated by the
      renormalization group technique. The "Van Hove" scenario of non-Fermi-liquid
      behavior for high-T(c) compounds can take place in a broad enough range of the
      hole concentrations. The results are in qualitative agreement with the recent
      angle-resolved photoemission spectroscopy data on La 2CuO (4).

PMID- 12190537
TI  - Anisotropy and interplane interactions in the dielectric response of graphite.
AB  - We determined the anisotropic dielectric response of graphite by means of time
      dependent density-functional theory and high-resolution valence electron energy
      loss spectroscopy. The calculated loss function was in very good agreement with
      the experiment for a wide range of momentum-transfer orientations with respect to
      the graphitic basal planes, provided that local-field effects were included in
      the response. The calculations also showed strong effects of the interlayer
      Coulomb interaction on the total pi+sigma plasmon. This finding must be taken
      into account for the explanation of recent loss spectra of carbon nanotube
      materials.

PMID- 12190538
TI  - Critical local-moment fluctuations, anomalous exponents, and omega/T scaling in
      the Kondo problem with a pseudogap.
AB  - Experiments in heavy-fermion metals and related theoretical work suggest that
      critical local-moment fluctuations can play an important role near a zero
      temperature phase transition. We study such fluctuations at the quantum critical
      point of a Kondo impurity model in which the density of band states vanishes as
      /epsilon/(r) at the Fermi energy (epsilon=0). The local spin response is
      described by a set of critical exponents that vary continuously with r. For
      0<r<1, the dynamical susceptibility at the critical point exhibits omega/T
      scaling with a fractional exponent, implying that the critical point is
      interacting.

PMID- 12190539
TI  - Anomalously broad Raman scattering spectrum due to two-magnon excitation in
      hexagonal YMnO3.
AB  - A strong and broad Raman scattering (RS) spectrum is observed from two-magnon
      processes in YMnO3. The spectrum is analyzed by taking account (i) the magnon
      exciton interaction and (ii) the magnon-phonon coupling in the intermediate
      state. Anomalous broadening of the RS is attributed to the large superexchange
      interaction between manganite ions and subsequent modification of magnons under
      the presence of the exciton and phonons in the intermediate state.

PMID- 12190540
TI  - Configurational entropy of network-forming materials.
AB  - We present a computationally efficient method to calculate the configurational
      entropy of network-forming materials. The method requires only the atomic
      coordinates and bonds of a single well-relaxed configuration. This is in contrast
      to the multiple simulations that are required for other methods to determine
      entropy, such as thermodynamic integration. We use our method to obtain the
      configurational entropy of well-relaxed networks of amorphous silicon and
      vitreous silica. For these materials we find configurational entropies of
      0.93k(B) and 0.88k(B) per silicon atom, respectively.

PMID- 12190542
TI  - Theoretical characterization of the ground and optically excited states of alpha'
      NaV2O5.
AB  - The character of the ground and optically excited states was investigated by
      quantum chemical calculations. We propose a rung ground state with V 3d(1)(xy)-O
      2p(1)(y)-V 3d(1)(xy) character, instead of the conventional picture of one
      unpaired electron shared by 2 V ions. The unpaired electron on O is low-spin
      coupled to the V d electrons and spin density is predicted to be localized on
      vanadium. The absorption peak at 0.9 eV is assigned to a state with similar
      orbital occupations but a different spin coupling scheme, resulting in spin
      density localized on the bridging oxygen.

PMID- 12190541
TI  - Hole-hole interaction effect in the conductance of the two-dimensional hole gas
      in the ballistic regime.
AB  - On a high-mobility two-dimensional hole gas (2DHG) in a GaAs/GaAlAs
      heterostructure we study the interaction correction to the Drude conductivity in
      the ballistic regime, k(B)Ttau/ variant Planck's over 2pi >1. It is shown that
      the "metallic" behavior of the resistivity (drho/dT>0) of the low-density 2DHG is
      caused by the hole-hole interaction effect in this regime. We find that the
      temperature dependence of the conductivity and the parallel-field
      magnetoresistance are in agreement with this description, and determine the Fermi
      liquid interaction constant Fsigma0 which controls the sign of drho/dT.

PMID- 12190543
TI  - Critical fluctuations in a mesoscopic superconducting ring.
AB  - The nonlocal magnetoconductivity fluctuations in a superconducting submicron
      ring, with radius comparable to the Ginzburg-Landau coherence length, are
      studied. The order parameter mode separation yields to the solution of the time
      dependent Ginzburg-Landau equation and the paraconductivity Fourier components
      are calculated in the vicinity of the critical temperature, including the
      critical fluctuation region. The homogeneous component has a logarithmic
      singularity at T(c) while the other components are found to be not singular.

PMID- 12190544
TI  - New spin-orbit-induced universality class in the integer quantum Hall regime.
AB  - Using heuristic arguments and numerical simulations it is argued that the
      critical exponent nu describing the localization length divergence at the integer
      quantum-Hall transition is modified in the presence of spin-orbit scattering with
      short-range correlations. The exponent is very close to nu=4/3, the percolation
      correlation length exponent, consistent with the prediction of a semiclassical
      argument. In addition, a band of weakly localized states is conjectured.

PMID- 12190545
TI  - Zener tunneling between landau orbits in a high-mobility two-dimensional electron
      gas.
AB  - Magnetotransport in a laterally confined two-dimensional electron gas (2DEG) can
      exhibit modified scattering channels owing to a tilted Hall potential.
      Transitions of electrons between Landau levels with shifted guiding centers can
      be accomplished through a Zener tunneling mechanism, and make a significant
      contribution to the magnetoresistance. A remarkable oscillation effect in weak
      field magnetoresistance has been observed in high-mobility 2DEGs in GaAs -Al Ga
      0.3As (0.7) heterostructures, and can be well explained by the Zener mechanism.

PMID- 12190546
TI  - Chemical design of direct-gap light-emitting silicon.
AB  - Quantum confinement effect has been the dominant approach guiding the search for
      light-emitting silicon. By first-principles total energy calculations of Si delta
      doped with oxygen layers, however, we show that this generally accepted mechanism
      is ineffective. Instead, a different mechanism is proposed based on defect
      engineering where the oxygen atoms chemically shift the valence band edge of Si
      away from the zone center, resulting in the desired optical functionality. Our
      calculation suggests new design principles for light-emitting silicon as well as
      providing the microscopic origin for the observed strong luminescence and band
      gap increase in the SiO(001) multi-delta-layers.

PMID- 12190547
TI  - Is the onset of high-temperature superconductivity associated with a dimensional
      crossover?
AB  - Angle-resolved ultraviolet photoemission spectroscopy (ARUPS) from high-T(c)
      superconductors shows an effective-mass renormalization and intense quasiparticle
      peaks close to the Fermi energy E(F), which change dramatically with temperature
      as T(c) is crossed. They are attributed to many-body effects, but their precise
      nature has been controversial until now. We find very similar spectral
      fingerprints, even with a similar temperature dependence albeit with much higher
      critical temperature, in a quasi-one-dimensional Br/Pt surface compound. The
      striking parallels support an interpretation based on spin-charge separation and
      are consistent with a dimensional crossover taking place at T(c).

PMID- 12190548
TI  - Zinc impurities in d-wave superconductors.
AB  - We study the two-dimensional Hubbard model with nonmagnetic Zn impurities modeled
      by binary diagonal disorder using quantum Monte Carlo within the dynamical
      cluster approximation. With increasing Zn content we find a strong suppression of
      d-wave superconductivity and an enhancement of antiferromagnetic spin
      correlations. T(c) vanishes linearly with Zn impurity concentration. The spin
      susceptibility changes from pseudogap to Curie-Weiss-like behavior indicating the
      existence of free magnetic moments in the Zn doped system. We interpret these
      results within the resonating-valence-bond picture.

PMID- 12190549
TI  - Topological origin of zero-energy edge states in particle-hole symmetric systems.
AB  - A criterion to determine the existence of zero-energy edge states is discussed
      for a class of particle-hole symmetric Hamiltonians. A "loop" in a parameter
      space is assigned for each one-dimensional bulk Hamiltonian, and its topological
      properties, combined with the chiral symmetry, play an essential role. It
      provides a unified framework to discuss zero-energy edge modes for several
      systems such as fully gapped superconductors, two-dimensional d-wave
      superconductors, and graphite ribbons. A variance of the Peierls instability
      caused by the presence of edges is also discussed.

PMID- 12190550
TI  - Origin of the peak-dip-hump line shape in the superconducting-state (pi,0)
      photoemission spectra of Bi2Sr2CaCu2O8.
AB  - From detailed high-resolution measurements of the photon energy dependence of the
      (pi,0) superconducting-state photoemission spectrum of the bilayer Bi high
      temperature superconductors, we show that the famous peak-dip-hump line shape is
      dominated by a superposition of spectral features originating from different
      electronic states which reside at different binding energies, but are each
      describable by essentially identical single-particle spectral functions. The
      previously identified bilayer-split CuO2 bands are the culprit: with the
      "superconducting" peak being due to the antibonding band, while the hump is
      mainly formed by its bonding bilayer-split counterpart.

PMID- 12190551
TI  - Exchange bias in spin-engineered double superlattices.
AB  - Exchange bias has been observed in sputtered magnetic double superlattices which
      consist of a ferromagnetically coupled superlattice grown on an
      antiferromagnetically (AF) coupled superlattice. This system exhibits a parallel
      domain wall, a spin flop transition, and exchange bias when the anisotropy is
      large in the AF block. This work shows that neither the domain wall nor the spin
      flop are directly related to exchange bias but that the anisotropy is essential.

PMID- 12190552
TI  - Magnetic structure, phase diagram, and a new type of spin-flop transition
      dominated by higher order interaction in a localized 5f system U3Pd20Si6.
AB  - The magnetic structure of the localized-5f uranium intermetallic compound
      U3Pd20Si6 has been determined by means of a neutron diffraction experiment. Our
      data demonstrate that this compound has a collinear coupling of the sublattice
      ordering of the uranium spins on the 4a and 8c sites. We conclude that higher
      order exchange and/or quadrupole interactions are necessary to stabilize this
      unique collinear structure. We discovered a new type of spin-flop transition
      against the uniaxial anisotropy induced by this collinear coupling.

PMID- 12190553
TI  - Magnon dispersion in the field-induced magnetically ordered phase of TlCuCl3.
AB  - The magnetic properties of the interacting dimer system TlCuCl3 are investigated
      within a bond-operator formulation. The observed field-induced staggered magnetic
      order perpendicular to the field is described as a Bose condensation of magnons
      which are linear combinations of dimer singlet and triplet modes. This technique
      accounts for the magnetization curve and for the field dependence of the magnon
      dispersion curves observed by high-field neutron scattering measurements.

PMID- 12190554
TI  - Order parameter to characterize valence-bond-solid states in quantum spin chains.
AB  - We propose an order parameter to characterize valence-bond-solid (VBS) states in
      quantum spin chains, given by the ground-state expectation value of a unitary
      operator appearing in the Lieb-Schultz-Mattis argument. We show that the order
      parameter changes the sign according to the number of valence bonds (broken
      valence bonds) at the boundary for periodic (open) systems. This allows us to
      determine the phase transition point in between different VBS states. We
      demonstrate this theory in the successive dimerization transitions of the bond
      alternating Heisenberg chains, using the quantum Monte Carlo method.

PMID- 12190555
TI  - Hybridization and bond-orbital components in site-specific X-ray photoelectron
      spectra of rutile TiO2.
AB  - We have determined the Ti and O components of the rutile TiO2 valence band using
      the method of site-specific x-ray photoelectron spectroscopy. Comparisons with
      calculations based on pseudopotentials within the local density approximation
      reveal the hybridization of the Ti 3d, 4s, and 4p states, and the O 2s and 2p
      states on each site. These chemical effects are observed due to the large
      differences between the angular-momentum dependent matrix elements of the
      photoelectron process.

PMID- 12190556
TI  - Polarization control of the nonlinear emission of semiconductor microcavities.
AB  - The degree of circular polarization ( Weierstrass p ) of the nonlinear emission
      in semiconductor microcavities is controlled by changing the exciton-cavity
      detuning. The polariton relaxation towards K approximately 0 cavitylike states is
      governed by final-state stimulated scattering. The helicity of the emission is
      selected due to the lifting of the degeneracy of the +/-1 spin levels at K
      approximately 0. At short times after a pulsed excitation Weierstrass p reaches
      very large values, either positive or negative, as a result of stimulated
      scattering to the spin level of lowest energy (+1/-1 spin for positive/negative
      detuning).

PMID- 12190557
TI  - Random piezoelectric field in real [001]-oriented strain-relaxed semiconductor
      heterostructures.
AB  - We work out a theory of piezoelectricity in an actual semiconductor
      heterostructure which is composed of a lattice-mismatched zinc-blende layer grown
      on a [001]-oriented substrate. In contrast to earlier theories, we predict a
      large density of fixed bulk piezoelectric charges, which are induced by strain
      fluctuations connected with interface roughness. The piezoelectric charges create
      a high electric field. The random piezoelectric field presents a conceptually new
      important scattering mechanism. The system of charge carriers in such a
      heterostructure becomes strongly disordered and includes generally both free
      electron-hole pairs near the interface and excitons far from it.

PMID- 12190558
TI  - Rippling patterns in aggregates of myxobacteria arise from cell-cell collisions.
AB  - Experiments with myxobacterial aggregates reveal standing waves called rippling
      patterns. Here these structures are modeled with a simple discrete model based on
      the interplay between migration and collisions of cells. Head-to-head collisions
      of cells result in cell reversals. To correctly reproduce the rippling patterns,
      a refractory phase after each cell reversal has to be assumed, during which
      further reversal is prohibited. The duration of this phase determines the
      wavelength and period of the ripple patterns as well as the reversal frequency of
      single cells.

PMID- 12190559
TI  - Colloidal dynamics on disordered substrates.
AB  - Using Langevin simulations, we examine driven colloids interacting with quenched
      disorder. For weak substrates the colloids form an ordered state and depin
      elastically. For increasing substrate strength, we find a sharp crossover to
      inhomogeneous depinning and a substantial increase in the depinning force,
      analogous to the peak effect in superconductors. The velocity versus driving
      force curve shows criticality at depinning, with a change in scaling exponent
      occurring at the order to disorder crossover. Upon application of a sudden pulse
      of driving force, pronounced transients appear in the disordered regime which are
      due to the formation of long-lived colloidal flow channels.

PMID- 12190560
TI  - Comment on "Simple one-dimensional model of heat conduction which obeys Fourier's
      law".

PMID- 12190562
TI  - Comment on "Fragmented condensate ground state of trapped weakly interacting
      Bosons in two dimensions".

PMID- 12190563
TI  - Comment on "Ionic conduction in glass: new information on the interrelation
      between the 'Jonscher behavior' and the 'Nearly constant-loss behavior' from
      broadband conductivity spectra".

PMID- 12190565
TI  - Comment on "Spin dynamics of the 2D spin 1 / 2 quantum antiferromagnet copper
      deuteroformate tetradeuterate (CFTD)".

PMID- 12190567
TI  - Bell-type inequalities for partial separability in N-particle systems and quantum
      mechanical violations.
AB  - We derive N-particle Bell-type inequalities under the assumption of partial
      separability, i.e., that the N-particle system is composed of subsystems which
      may be correlated in any way (e.g., entangled) but which are uncorrelated with
      respect to each other. These inequalities provide, upon violation, experi
      mentally accessible sufficient conditions for full N-particle entanglement, i.e.,
      for N-particle entanglement that cannot be reduced to mixtures of states in which
      a smaller number of particles are entangled. The inequalities are shown to be
      maximally violated by the N-particle Greenberger-Horne-Zeilinger states.

PMID- 12190568
TI  - Testing statistical bounds on entanglement using quantum chaos.
AB  - Previous results indicate that while chaos can lead to substantial entropy
      production, thereby maximizing dynamical entanglement, this still falls short of
      maximality. Random matrix theory modeling of composite quantum systems,
      investigated recently, entails a universal distribution of the eigenvalues of the
      reduced density matrices. We demonstrate that these distributions are realized in
      quantized chaotic systems by using a model of two coupled and kicked tops. We
      derive an explicit statistical universal bound on entanglement, which is also
      valid for the case of unequal dimensionality of the Hilbert spaces involved, and
      show that this describes well the bounds observed using composite quantized
      chaotic systems such as coupled tops.

PMID- 12190569
TI  - Oscillatory decay of a two-component bose-einstein condensate.
AB  - We study the decay of a two-component Bose-Einstein condensate with negative
      effective interaction energy. With a decreasing atom number due to losses, the
      atom-atom interaction becomes less important and the system undergoes a
      transition from a bistable Josephson regime to the monostable Rabi regime,
      displaying oscillations in phase and number. We study the equations of motion and
      derive an analytical expression for the oscillation amplitude. A quantum
      trajectory simulation reveals that the classical description fails for low loss
      rates, as expected from analytical considerations. Observation of the proposed
      effect will provide evidence for negative effective interaction.

PMID- 12190570
TI  - In- and outbound spreading of a free-particle s-wave.
AB  - We show that a free quantum particle in two dimensions with zero angular momentum
      (s wave) in the form of a ring-shaped wave packet feels an attraction towards the
      center of the ring, leading first to a contraction followed by an expansion. An
      experiment to demonstrate this effect is also outlined.

PMID- 12190571
TI  - Local and occupation time of a particle diffusing in a random medium.
AB  - We consider a particle moving in a one-dimensional potential which has a
      symmetric deterministic part and a quenched random part. We study analytically
      the probability distributions of the local time (spent by the particle around its
      mean value) and the occupation time (spent above its mean value) within an
      observation time window of size t. In the absence of quenched randomness, these
      distributions have three typical asymptotic behaviors depending on whether the
      deterministic potential is unstable, stable, or flat. These asymptotic behaviors
      are shown to get drastically modified when the random part of the potential is
      switched on, leading to the loss of self-averaging and wide sample to sample
      fluctuations.

PMID- 12190572
TI  - Biorthogonal decomposition techniques unveil the nature of the irregularities
      observed in the solar cycle.
AB  - We present a biorthogonal decomposition of the temporal and latitudinal
      distribution of sunspots recorded since 1874. We show that the butterfly diagrams
      can be interpreted as the result of approximately constant amplitudes and phases
      of two oscillations with periods close to 22 years. Our analysis reveals clear
      evidence of the absence of low-dimensional chaos, at least for the time scales
      that can be analyzed with this database. This result suggests that the
      spatiotemporal irregularities observed in the solar cycle are due to the
      superposition of regular structures with a stochastic background.

PMID- 12190573
TI  - New upper limit on the total neutrino mass from the 2 degree field galaxy
      redshift survey.
AB  - We constrain f(nu) identical with Omega(nu)/Omega(m), the fractional contribution
      of neutrinos to the total mass density in the Universe, by comparing the power
      spectrum of fluctuations derived from the 2 Degree Field Galaxy Redshift Survey
      with power spectra for models with four components: baryons, cold dark matter,
      massive neutrinos, and a cosmological constant. Adding constraints from
      independent cosmological probes we find f(nu)<0.13 (at 95% confidence) for a
      prior of 0.1<Omega(m)<0.5, and assuming the scalar spectral index n=1. This
      translates to an upper limit on the total neutrino mass m(nu,tot)<1.8 eV for
      "concordance" values of Omega(m) and the Hubble constant.

PMID- 12190574
TI  - The Friedmann equation in brane-world scenarios.
AB  - The Friedmann law on the brane generically depends quadratically on the brane
      energy density and involves a "dark radiation" term due to the bulk Weyl tensor.
      Despite its unfamiliar form, we show how it can be derived from a standard four
      dimensional Brans-Dicke theory at low energy. In particular, the dark radiation
      term is found to depend linearly on the brane energy densities. For any equation
      of state on the branes, the radion evolves such as to generate radiation
      dominated cosmology. The radiation-dominated era is conventional and consistent
      with nucleosynthesis.

PMID- 12190576
TI  - Experimental investigation of high-energy photon splitting in atomic fields.
AB  - Data analysis of an experiment in which photon splitting in atomic fields was
      observed is presented. The experiment was performed at the tagged photon beam of
      the ROKK-1M facility at the VEPP-4M collider. In the energy region of 120-450
      MeV, statistics of 1.6x10(9) photons incident on the BGO target was collected.
      About 400 candidate photon-splitting events were reconstructed. Within the
      attained experimental accuracy, the experimental results are consistent with the
      calculated exact atomic-field cross section. The predictions obtained in the Born
      approximation differ significantly from the experimental results.

PMID- 12190577
TI  - Experimental study of the radiative decays K+-->mu(+)nue(+)e(-) and K+-
      >e(+)nue(+)e(-).
AB  - Experiment 865 at the Brookhaven Alternating Gradient Synchrotron obtained 410 K+
      ->e(+)nue(+)e(-) and 2679 K+-->mu(+)nue(+)e(-) events including 10% and 19%
      background. The branching ratios were measured to be [2.48+/-0.14(stat)+/
      0.14(syst)]x10(-8) (m(ee)>150 MeV) and (7.06+/-0.16+/-0.26)x10(-8) (m(ee)>145
      MeV), respectively. Results for the decay form factors are presented.

PMID- 12190578
TI  - 2H(e,e(')p)n reaction at high recoil momenta.
AB  - The 2H(e,e(')p)n cross section was measured in Hall A of the Thomas Jefferson
      National Accelerator Facility near the top of the quasielastic peak (x(Bj)=0.964)
      at a four-momentum transfer squared, Q(2)=0.665 (GeV/c) (2) (omega=0.368 GeV,
      W=2.057 GeV), and for recoil momenta up to 550 MeV/c. The measured cross section
      deviates by 1-2sigma from a state-of-the-art calculation at low recoil momenta.
      At high recoil momenta the cross section is well described by the same
      calculation; however, in this region, final-state interactions and interaction
      currents are predicted to be large, and alternative choices of nucleon-nucleon
      potential and nucleon current operator may result in significant spread in the
      calculations.

PMID- 12190579
TI  - Accumulation of cold cesium molecules via photoassociation in a mixed atomic and
      molecular trap.
AB  - We have realized a mixed atomic and molecular trap, constituted by a Cs vapor
      cell magneto-optical trap and a quadrupolar magnetic C s(2) trap, using the same
      magnetic field gradient. We observed the trapping of 2x 10(5) molecules, formed
      and accumulated in the metastable a (3)Sigma(+ )(u) state at a temperature of
      30+/-10 microK through a approximately 150 ms photoassociation process. The
      lifetime of the trapped molecular cloud limited by the Cs background gas pressure
      is on the order of 1 s.

PMID- 12190580
TI  - Analytic solution for the nondegenerate quantum control problem.
AB  - We present an analytic solution for the nondegenerate quantum control problem,
      i.e., the transfer of a deliberate amount of population, 0%-100%, between
      arbitrary initial Psi(t)> and final Psi'(t)> states, which can be expanded in
      terms of nondegenerate energy eigenstates k>. The solution constitutes a robust
      two-photon multicomponent adiabatic passage, via an intermediate eigenstate 0>,
      which relies on three types of "null states."

PMID- 12190581
TI  - Resonant transmission of microwaves through a narrow metallic slit.
AB  - Strong resonant transmission of microwave radiation through a very narrow (much
      less than the radiation wavelength) metallic slit is recorded. The results show
      that a set of resonant self-coupled surface plasmons are excited within the small
      gap, giving a Fabry-Perot-like behavior in accord with analytical results
      published earlier [Y. Takakura, Phys. Rev. Lett. 86, 5601 (2001)]. The metallic
      slit, formed by two thick metal plates spaced apart by tens of microns, is
      inserted in a wavelength-sized aperture. On resonance the transmissivity through
      the metal slit is more than 2 orders of magnitude greater than the radiation
      impinging on the slit area.

PMID- 12190582
TI  - Experimental test of a trace formula for a chaotic three-dimensional microwave
      cavity.
AB  - We have measured resonance spectra in a superconducting microwave cavity with the
      shape of a three-dimensional generalized Bunimovich stadium billiard and analyzed
      their spectral fluctuation properties. The experimental length spectrum exhibits
      contributions from periodic orbits of nongeneric modes and from unstable periodic
      orbits of the underlying classical system. It is well reproduced by our
      theoretical calculations based on the trace formula derived by Balian and
      Duplantier for chaotic electromagnetic cavities.

PMID- 12190583
TI  - Wall-enhanced convection in vibrofluidized granular systems.
AB  - An event-driven molecular dynamics simulation of inelastic hard spheres contained
      in a cylinder and subject to strong vibration reproduces accurately experimental
      results [R. D. Wildman et al., Phys. Rev. Lett. 86, 3304 (2001)] for a system of
      vibrofluidized glass beads. In particular, we are able to obtain the velocity
      field and the density and temperature profiles observed experimentally. In
      addition, we show that the appearance of convection rolls is strongly influenced
      by the value of the sidewall-particle restitution coefficient. Suggestions for
      observing more complex convection patterns are proposed.

PMID- 12190584
TI  - Turbulentlike fluctuations in quasistatic flow of granular media.
AB  - We analyze particle velocity fluctuations in a simulated granular system
      subjected to homogeneous quasistatic shearing. We show that these fluctuations
      share the following scaling characteristics of fluid turbulence in spite of their
      different physical origins: (i) scale-dependent probability distribution with non
      Gaussian broadening at small time scales; (ii) spatial power spectrum of the
      velocity field showing a power-law decay, reflecting long-range correlations and
      the self-affine nature of the fluctuations; and (iii) superdiffusion of particles
      with respect to the mean background flow.

PMID- 12190585
TI  - Origin of a repose angle: kinetics of rearrangement for granular materials.
AB  - A microstructural theory of dense granular materials is presented, based on two
      main ideas: first, that macroscopic shear results from activated local
      rearrangements at a mesoscopic scale; second, that the update frequency of
      microscopic processes is determined by granular temperature. In a shear cell, the
      resulting constitutive equations account for Bagnold's scaling and for the
      existence of a Coulomb criterion. In a granular flow down an inclined plane, they
      account for the rheology observed in experiments [Phys. Fluids 11, 542 (1999)]]
      and for temperature and velocity profiles measured numerically [Europhys. Lett.
      56, 214 (2001)]] [Phys. Rev. E 64, 051302 (2001)]].

PMID- 12190586
TI  - Quasi-Gaussian statistics of hydrodynamic turbulence in 4 / 3 +epsilon
      dimensions.
AB  - The statistics of two-dimensional turbulence exhibit a riddle: the scaling
      exponents in the regime of inverse energy cascade agree with the K41 theory of
      turbulence far from equilibrium, but the probability distribution functions are
      close to Gaussian-like in equilibrium. The skewness S identical with
      S3(R)/S(3/2)(2)(R) was measured as S (exp) approximately 0.03. This contradiction
      is lifted by understanding that two-dimensional turbulence is not far from a
      situation with equipartition of enstrophy, which exists as true thermodynamic
      equilibrium with K41 exponents in space dimension of d= 4 / 3. We evaluate the
      skewness S( d) for 4 / 3 < or =d< or =2, showing that S(d)=0 at d= 4 / 3, and
      that it remains as small as S (exp) in two dimensions.

PMID- 12190587
TI  - Mesoscopic modeling of slip motion at fluid-solid interfaces with heterogeneous
      catalysis.
AB  - The onset of slip motion at fluid-solid boundaries is investigated as a function
      of the reflectivity of the solid wall by means of a mesoscopic lattice Boltzmann
      model. Substantial slip flow is observed for reflectivity values below a critical
      threshold. It is shown that this slip flow may significantly affect the
      conversion efficiency of catalytic microchannels.

PMID- 12190589
TI  - Evolution of lower-hybrid-driven current during the formation of an internal
      transport barrier.
AB  - Evolution of the lower-hybrid(LH)-driven current profile was measured during the
      formation of an internal transport barrier (ITB) in a reversed magnetic shear
      discharge. As the ITB developed, the initially centrally peaked LH-driven current
      profile gradually turned hollow and was sometimes accompanied by an off-axis peak
      in the electron temperature profile. These observations indicate the
      concentration of LH power deposition to the ITB for this case as a result of
      nonlinear coupling between the LH waves and the target plasma.

PMID- 12190588
TI  - Single-file transport of water molecules through a carbon nanotube.
AB  - Recent molecular dynamics simulations of water transport through the interior
      channel of a carbon nanotube in contact with an aqueous reservoir showed that
      conduction occurred in bursts with collective water motion. A continuous-time
      random-walk model is used to describe concerted transport through channels
      densely filled with molecules in a single-file arrangement, as also found in
      zeolites, as well as ion channels and aquaporins in biological membranes.
      Theoretical predictions for different collective properties of the single-file
      transport agree with the simulation results.

PMID- 12190590
TI  - The role of lower-hybrid-wave collapse in the auroral ionosphere.
AB  - In regions where lower-hybrid solitary structures (LHSS) are observed, the
      character of auroral lower-hybrid turbulence (LHT) (0-20 kHz) is investigated
      using the amplitude probability distribution of the electric field. The observed
      probability distributions are accurately described by a Rayleigh distribution
      with two degrees of freedom. The statistics of the LHT exhibit no evidence of the
      global modulational instability or self-similar wave collapse. We conclude that
      nucleation and resonant scattering in preexisting density depletions are the
      processes responsible for LHSS in auroral LHT.

PMID- 12190591
TI  - Experimental observation of radiation from cherenkov wakes in a magnetized
      plasma.
AB  - A proof-of-principle experiment demonstrates the generation of radiation from the
      Cherenkov wake excited by an ultrashort- and ultrahigh-power pulse laser in a
      perpendicularly magnetized plasma. The frequency of the radiation is in the
      millimeter range (up to 200 GHz). The intensity of the radiation is proportional
      to the magnetic field intensity as expected by theory. Polarization of the
      emitted radiation is also detected. The difference in the frequency of the
      emitted radiation between these experiments and previous theory can be explained
      by the electrons' oscillation in the electric field of a narrow column of ions in
      the focal region.

PMID- 12190592
TI  - Picosecond x-ray laser interferometry of dense plasmas.
AB  - We present the first results from picosecond interferometry of dense laser
      produced plasmas using a soft x-ray laser. The picosecond duration and short
      wavelength of the 14.7 nm Ni-like Pd laser mitigates effects associated with
      motion blurring and refraction through millimeter-scale plasmas. This enables
      direct measurement of the electron-density profile to within 10 microm of the
      target surface. A series of high-quality two-dimensional (2D) density
      measurements provide unambiguous characterization of the time evolution in a fast
      evolving plasma suitable for validation of existing 1D and 2D hydrodynamic codes.

PMID- 12190594
TI  - Demixing transition in a quasi-two-dimensional surface-frozen layer.
AB  - A thin/thick transition was observed by x-ray reflectivity in a surface-frozen
      crystalline bilayer on the surface of a molten binary mixture of long alcohols.
      This rare example of a solid-solid phase transition in a quasi-2D system is shown
      to result from an abrupt temperature-driven change in the layer's composition,
      kinetically enabled by the layer's ability to exchange molecules with the
      underlying 3D liquid bulk. Mean-field thermodynamics yields a Gibbs-adsorption
      like expression which accounts very well for the transition.

PMID- 12190593
TI  - Deuterium-deuterium fusion dynamics in low-density molecular-cluster jets
      irradiated by intense ultrafast laser pulses.
AB  - Following the interaction of superintense, short pulse lasers and plasmas, ions
      can be accelerated to velocities sufficient to drive nuclear fusion reactions, in
      particular, by the process of Coulomb explosion of clusters [T. Ditmire, Nature
      (London) 398, 491 (1999)]]. We show here how short bursts of neutrons can be
      produced using a jet of low-density deuterated methane clusters. Ion velocity
      distributions were simultaneously measured by a Thomson parabola mass
      spectrometer, demonstrating deuteron energies up to 120 keV. We show that, in
      such conditions, nuclear fusion will occur not only in the hot plasma core, but
      also in the cold outer region by collision processes.

PMID- 12190595
TI  - Triple minima in the free energy of semiflexible polymers.
AB  - We study the free energy of the worm-like-chain model, in the constant-extension
      ensemble, as a function of the stiffness lambda for finite chains of length L. We
      find that the polymer properties obtained in this ensemble are qualitatively
      different from those obtained using constant-force ensembles. In particular, we
      find that as we change the stiffness parameter, t=L/lambda, the polymer makes a
      transition from the flexible to the rigid phase and there is an intermediate
      regime of parameter values where the free energy has three minima and both phases
      are stable. This leads to interesting features in the force-extension curves.

PMID- 12190575
TI  - Measurement of the branching fraction and CP content for the decay B0-->D(*+)D(*
      ).
AB  - We report a measurement of the branching fraction of the decay B0-->D(*+)D(*-)
      and of the CP-odd component of its final state using the BABAR detector. With
      data corresponding to an integrated luminosity of 20.4 fb (-1) collected at the
      Upsilon(4S) resonance during 1999-2000, we have reconstructed 38 candidate signal
      events in the mode B0-->D(*+)D(*-) with an estimated background of 6.2+/-0.5
      events. From these events, we determine the branching fraction to be B(B0-
      >D(*+)D(*-))=[8.3+/-1.6(stat)+/-1.2(syst)]x10(-4). The measured CP-odd fraction
      of the final state is 0.22+/-0.18(stat)+/-0.03(syst).

PMID- 12190596
TI  - Rejuvenation and overaging in a colloidal glass under shear.
AB  - We report the modifications of the microscopic dynamics of a colloidal glass
      submitted to shear. We use multispeckle diffusing wave spectroscopy to monitor
      the evolution of the spontaneous slow relaxation processes after the samples have
      been submitted to various straining. We show that high shear rejuvenates the
      system and accelerates its dynamics, whereas moderate shear over-ages the system.
      We analyze these phenomena within the frame of the Bouchaud's trap model.

PMID- 12190597
TI  - Self-diffusion rates in Al from combined first-principles and model-potential
      calculations.
AB  - Monovacancy diffusion alone dominates over diffusion due to divacancies and
      interstitials in Al for all temperatures up to the melting point. Deviations from
      a single Arrhenius dependence are due to anharmonicity. The conclusion is based
      on a combination of theoretical methods, from density functional theory to
      thermodynamic integration, without fitting to experimental data. The calculated
      diffusion rate agrees with experimental data over 11 orders of magnitude.

PMID- 12190598
TI  - Shot noise in ballistic quantum dots with a mixed classical phase space.
AB  - We investigate shot noise for quantum dots whose classical phase space consists
      of both regular and chaotic regions. The noise is systematically suppressed below
      the universal value of fully chaotic systems, by an amount which varies with the
      positions of the leads. We analyze the dynamical origin of this effect by a novel
      way to incorporate diffractive impurity scattering. The dependence of the shot
      noise on the scattering rate shows that the suppression arises due to the
      deterministic nature of transport through regular regions and along short chaotic
      trajectories. Shot noise can be used to probe phase-space structures of quantum
      dots with generic classical dynamics.

PMID- 12190600
TI  - Multiple scattering of fractionally charged quasiparticles.
AB  - We employ shot noise measurements to characterize the effective charge of
      quasiparticles, at filling factor nu=1/3 of the fractional quantum Hall regime,
      as they scatter from an array of identical weak backscatterers. Upon scattering,
      quasiparticles are known to bunch, e.g., only three e/3 charges, or "electrons"
      are found to traverse a rather opaque potential barrier. We find here that the
      effective charge scattered by an array of scatterers is determined by the
      scattering strength of an individual scatterer and not by the combined scattering
      strength of the array, which can be very small. Moreover, we also rule out
      intraedge equilibration of e/3 quasiparticles over a length scale of hundreds of
      microns.

PMID- 12190599
TI  - Shot-noise-induced random telegraph noise in shuttle current.
AB  - Random telegraph noise in the electric current produced by shot noise is
      predicted for an array of movable colloid particles by Monte Carlo and molecular
      dynamics calculations. The electron transport is attributed to the shuttle
      mechanism where moving colloid particles carry charges. The colloid-particle
      motion induced by the source-drain voltage shows periodic and/or quasiperiodic
      vibrations, and the current value depends on the vibration modes. Shot noise that
      is uncorrelated with the colloid-particle motion causes transitions between the
      periodic and quasiperiodic vibration modes, resulting in random switching between
      the current levels corresponding to the vibration modes.

PMID- 12190601
TI  - Current-voltage curves of atomic-sized transition metal contacts: an explanation
      of why Au is Ohmic and Pt is not.
AB  - We present an experimental study of current-voltage (I-V) curves on atomic-sized
      Au and Pt contacts formed under cryogenic vacuum (4.2 K). Whereas I-V curves for
      Au are almost Ohmic, the conductance G=I/V for Pt decreases with increasing
      voltage, resulting in distinct nonlinear I-V behavior. The experimental results
      are compared with first principles density functional theory calculations for Au
      and Pt, and good agreement is found. The difference in conductance properties for
      Pt vs Au can be explained by the underlying electron valence structure: Pt has an
      open d shell while Au has not.

PMID- 12190602
TI  - Vortices with fractional flux in two-gap superconductors and in extended faddeev
      model.
AB  - We discuss linear topological defects allowed in two-gap superconductors and
      equivalent extended Faddeev model. We show that, in these systems, there exist
      vortices which carry an arbitrary fraction of magnetic flux quantum. Besides
      that, we discuss topological defects which do not carry magnetic flux and
      describe features of ordinary one-magnetic-flux-quantum vortices in the two-gap
      system. The results could be relevant for the newly discovered two-band
      superconductor MgB2.

PMID- 12190603
TI  - Two crossovers in the Pseudogap regime of YBa 2Cu 3O (7-delta) superconductors
      observed by ultrafast spectroscopy.
AB  - We have investigated the temperature dependence of the optical reflectivity on a
      femtosecond scale in a near optimally doped YBa 2Cu 3O (7-delta) superconductor.
      The combined study of the lattice and carrier dynamics at temperatures above T(c)
      allows us to identify two crossover temperatures in the normal state, giving
      evidence for an inhomogeneity of the pseudogap regime. These crossovers exhibit a
      clear hysteresis behavior depending on the direction of temperature change. The
      carrier and lattice dynamics within the crossover regimes show distinct
      differences from and similarities to the superconducting state, which may help in
      choosing between the competing theories for the pseudogap state.

PMID- 12190604
TI  - Spin and charge order around vortices and impurities in high-T(c)
      superconductors.
AB  - A comparative study is made for the spin and charge structure around
      superconducting vortices and unitary impurities, by solving self-consistently an
      effective Hamiltonian including interactions for both antiferromagnetic spin
      density wave (SDW) and d-wave superconducting orderings. Around vortices, we show
      the induction of an SDW two-dimensionally modulated with a period of eight
      lattice constants (8a(0)) and an associated charge-density wave (CDW) with a
      period of 4a(0), which explains very well recent experimental observations. In
      the case of unitary impurities, an SDW modulation with identical periodicity, but
      without an associated CDW, is also predicted.

PMID- 12190605
TI  - Observation of splintered Josephson vortices at grain boundaries in
      YBa(2)Cu(3)O(7-delta).
AB  - We have directly observed well-separated Josephson vortex splinters with
      unquantized magnetic flux at asymmetric 45 degrees grain boundaries in
      YBa(2)Cu(3)O(7-delta) films by imaging magnetic flux with scanning SQUID
      microscopy. The existence of these splinter vortices has been predicted and is
      well described by a model based on dx(2)(-y(2)) pairing symmetry and facetting of
      the grain boundary on a length scale shorter than the Josephson penetration
      depth.

PMID- 12190606
TI  - Low energy excitation and scaling in Bi(2)Sr(2)Ca(n-1)Cu(n)O(2n+4) (n=1-3): angle
      resolved photoemission spectroscopy.
AB  - Angle-resolved photoemission spectroscopy (ARPES) has been performed on the
      single- to triple-layered Bi-family high-T (c) superconductors (Bi(2)Sr(2)Ca(n
      1)Cu(n)O(2n+4), n=1-3). We found a sharp coherent peak as well as a pseudogap at
      the Fermi level in the triple-layered compound. Comparison among three compounds
      has revealed a universal rule that the characteristic energies of superconducting
      and pseudogap behaviors are scaled with the maximum T (c).

PMID- 12190607
TI  - Shear-excited sound in magnetic fluid.
AB  - Perceptible sound is shown to be excited in ferrofluids by the shear motion of a
      rigid plate, if the fluid is exposed to a magnetic field oblique both to the
      plate and to the direction of propagation. This is in contrast to other fluids,
      including anisotropic ones such as nematic liquids.

PMID- 12190608
TI  - Multiple field-induced phase transitions in the geometrically frustrated dipolar
      magnet: Gd(2) Ti(2)O(7).
AB  - Field-driven phase transitions generally arise from competition between Zeeman
      energy and exchange or crystal-field anisotropy. Here we present the phase
      diagram of a frustrated pyrochlore magnet Gd(2)Ti(2)O(7), where crystal-field
      splitting is small compared to the dipolar energy. We find good agreement between
      zero-temperature critical fields and those obtained from a mean-field model.
      Here, dipolar interactions couple real space and spin space, so the transitions
      in Gd(2)Ti(2)O(7) arise from field-induced "cooperative anisotropy," reflecting
      the broken spatial symmetries of the pyrochlore lattice.

PMID- 12190609
TI  - Dynamics of inter-landau-level excitations of a two-dimensional electron gas in
      the quantum Hall regime.
AB  - The femtosecond inter-Landau-level dynamics of a two-dimensional electron gas in
      a large magnetic field is investigated by degenerate four-wave mixing on
      modulation doped quantum wells. We observe a large transfer of oscillator
      strength to the lowest Landau level, and unusual dynamics due to Coulomb
      correlation. We interpret the effects using a model based on shakeup of the
      electron gas.

PMID- 12190610
TI  - Observation of nanoscale 180 degrees stripe domains in ferroelectric PbTiO3 thin
      films.
AB  - We report the observation of periodic 180 degrees stripe domains below the
      ferroelectric transition in thin films. Epitaxial PbTiO3 films of thickness d=1.6
      to 42 nm on SrTiO3 substrates were studied using x-ray scattering. Upon cooling
      below T(C), satellites appeared around Bragg peaks indicating the presence of 180
      degrees stripe domains of period Lambda=3.7 to 24 nm. The dependence of Lambda on
      d agrees well with theory including epitaxial strain effects, while the
      suppression of T(C) for thinner films is significantly larger than that expected
      solely from stripe domains.

PMID- 12190611
TI  - Deterministic single-photon source for distributed quantum networking.
AB  - A sequence of single photons is emitted on demand from a single three-level atom
      strongly coupled to a high-finesse optical cavity. The photons are generated by
      an adiabatically driven stimulated Raman transition between two atomic ground
      states, with the vacuum field of the cavity stimulating one branch of the
      transition, and laser pulses deterministically driving the other branch. This
      process is unitary and therefore intrinsically reversible, which is essential for
      quantum communication and networking, and the photons should be appropriate for
      all-optical quantum information processing.

PMID- 12190612
TI  - Photon statistics and dynamics of fluorescence resonance energy transfer.
AB  - We report high time-resolution measurements of photon statistics from pairs of
      dye molecules coupled by fluorescence resonance energy transfer (FRET). In
      addition to quantum-optical photon antibunching, we observe photon bunching on a
      time scale of several nanoseconds. We show by numerical simulation that
      configuration fluctuations in the coupled fluorophore system could account for
      minor deviations of our data from predictions of basic Forster theory. With
      further characterization we believe that FRET photon statistics could provide a
      unique tool for studying DNA mechanics on time scales from 10(-9)-10(-3) s.

PMID- 12190613
TI  - Multiscale entropy analysis of complex physiologic time series.
AB  - There has been considerable interest in quantifying the complexity of physiologic
      time series, such as heart rate. However, traditional algorithms indicate higher
      complexity for certain pathologic processes associated with random outputs than
      for healthy dynamics exhibiting long-range correlations. This paradox may be due
      to the fact that conventional algorithms fail to account for the multiple time
      scales inherent in healthy physiologic dynamics. We introduce a method to
      calculate multiscale entropy (MSE) for complex time series. We find that MSE
      robustly separates healthy and pathologic groups and consistently yields higher
      values for simulated long-range correlated noise compared to uncorrelated noise.

PMID- 12190614
TI  - Unfolding proteins under external forces: a solvable model under the self
      consistent pair contact probability approximation.
AB  - We extend a model of Micheletti et al. [Phys. Rev. Lett. 87, 088102 (2001)]] used
      to study protein con-formations to the case in which there is an external force
      field. Under the self-consistent pair contact probability approximation, this
      residue-level resolution model can still be solved under pulling forces. We
      implement the algorithm using heterogeneous parameters and study the force
      induced unfolding of a helical segment from the protein transformylase and of the
      beta-stranded domains from the protein titin. The results are qualitatively
      consistent with the results from more expensive, atomistic dynamics simulation.
      Despite the mean-field-like approach, we observed a sharp and cooperative
      unfolding transition.

PMID- 12190615
TI  - Comment on "Solution of the relativistic Dirac-Morse problem".

PMID- 12190616
TI  - Comment on "Spin, gravity, and inertia".

PMID- 12190618
TI  - Autophosphorylation kinetics of protein kinases.
AB  - Protein kinases play a central role in cellular signal transduction, by
      transmitting biochemical information between activated membrane-bound receptors
      and physiological target proteins. In addition to phosphorylating other proteins,
      almost all protein kinases catalyse autophosphorylation reactions (i.e. reactions
      in which the kinase serves as its own substrate). The autophosphorylation
      reactions can be intramolecular or intermolecular. In the present study, a
      detailed kinetic analysis of the intermolecular autophosphorylation reaction is
      presented. On the basis of the kinetic equations, a new procedure is developed to
      evaluate the kinetic parameters of the autophosphorylation reaction. This method
      was used to analyse the intermolecular autophosphorylation of an S6/H4 kinase
      from human placenta. At a fixed ATP concentration of 0.125 mM, the apparent
      catalytic-centre activity (turnover number; k (cat)) and apparent Michaelis
      Menten constant ( K (m)) for the autophosphorylation reaction were determined to
      be 0.91 min(-1) and 0.86 microM respectively.

PMID- 12190619
TI  - Hair dye-sensitized hairdressers: the cross-reaction pattern with new generation
      hair dyes.
AB  - Hair dye allergies are a frequent cause of occupational skin disease among
      hairdressers. Conventional hair dyes contain 4-phenylenediamine (PPD), 2, 5
      diaminotoluene sulfate (DTS) and 2-nitro-4-phenylenediamine (ONPPD) as allergens.
      In new generation hair dyes, FD & C and D & C dyes are used in the hair dye
      formulations. This study investigated the cross-reaction pattern of new
      generation hair dyes among hairdressers (n = 40) with a known allergy to PPD
      and/or DTS and/or ONPPD. In the 40 hairdressers no positive reactions were
      observed to the single FD & C and D & C dyes. In two hairdressers, doubtful
      reactions were observed to one or more of the hair dye formulations. The data
      from this study suggest that for hairdressers sensitized to PPD and/or DTS and/or
      ONPPD this new generation of hair dyes is a safe alternative for use in their
      salons.

PMID- 12190620
TI  - Multicentre study of fragrance allergy in Hungary. Immediate and late type
      reactions.
AB  - The authors followed the frequency of fragrance contact sensitization in Hungary
      in a multicentre study in the years 1998 and 1999. A total of 3,604 patients were
      tested with fragrance mix (FM), and positive reactions were observed in 294
      (8.2%). In 160 FM hypersensitive patients, the study was continued with patch
      testing of the mix constituents (cinnamic alcohol, cinnamic aldehyde, eugenol,
      amyl cinnamic aldehyde, hydroxycitronellal, geraniol, isoeugenol, oak moss
      absolute). Of the patients tested, 70.6% produced positive reactions to the
      constituents. FM contact sensitization was mainly observed in female patients
      (74.4%). The incidence of contact urticaria in FM hypersensitive patients was
      6.1%. Simultaneous patch test trials of other environmental contact allergens, in
      both early and late evaluations, mainly confirmed hypersensitivity reactions to
      balsams. Female dominance of hypersensitivity reactions observed during testing
      the individual components of the mix was striking (82.4%). In positive skin
      reactions, cinnamic alcohol, isoeugenol and oak moss provoked skin symptoms most
      frequently. We also tested the 104 patients who produced negative reactions to FM
      with the constituent individual allergens, with 11.9% positive incidence. The
      clinical symptoms of the patients were above all manifest in the form of contact
      eczema, located on the hands, face, eyelids and axillae. With this study, the
      authors, members of the Hungarian Contact Dermatitis Research Group, call
      attention to one of the most frequent allergens in the environment.

PMID- 12190621
TI  - Effect of a lipid-rich emollient containing ceramide 3 in experimentally induced
      skin barrier dysfunction.
AB  - In the present study we compared the effect of a ceramide 3-containing emollient
      (Locobase(R) Repair) with a control emollient (vaselinum album/cremor lanette
      ana) and untreated damaged skin using clinical, bioengineering and
      immunohistochemical methods in two different models of experimentally induced
      skin barrier dysfunction. In model A (n = 13) skin barrier dysfunction was
      inflicted at three investigation sites by tape stripping. In model B (n = 13) the
      volunteers were patch tested at three investigation sites with sodium dodecyl
      sulphate (0.2%) for 4 h a day for 4 consecutive days. The investigation sites
      were treated once a day with the above-mentioned agents. Irritant reaction was
      assessed daily by erythema scoring and measurements of transepidermal water loss
      (TEWL). After 5D, punch biopsies were taken from all sites. Immunohistochemical
      assessment was carried out with respect to epidermal proliferation, epidermal
      differentiation and Langerhans cells. Tape stripping resulted in an erythematous
      reaction and an increase of TEWL associated with up-regulation of cycling cells,
      involucrin and expression of cytokeratin 16. At day 4, ceramide 3-containing
      emollient significantly decreased (p < 0.03) the erythema score, TEWL and cycling
      cells in comparison with the untreated site. Repetitive exposure to SDS induced a
      variable degree of erythema, gradual increase of TEWL, an increase of cycling
      cells, and up-regulation of involucrin, E-FABP and SKALP. The treatment with the
      control emollient significantly prevented erythema, increase of TEWL and cycling
      cells at day 4 compared to the untreated site. In summary, the present study
      demonstrated that both tested emollients improve skin barrier in different
      conditions compared to the untreated skin. There is some indication that
      formulations containing skin-related lipids might be of benefit in barrier
      disruption following tape stripping. Different models and clinical trials are
      needed to establish the usefulness in specific conditions of emollients
      containing skin-related lipids.

PMID- 12190622
TI  - Occupational dermatoses among fibreglass-reinforced plastics factory workers.
AB  - Fibreglass-reinforced plastics (FRP) factory workers are at high risk of
      developing occupational dermatoses because of their exposure to many chemicals
      used in the manufacture of plastics as well as to glass fibre or dust. Patch
      tests were carried out on 29 workers involved in FRP manufacturing processes
      where unsaturated polyester (UP) resin was used, to investigate the causes of
      their skin problems. Of the 22 workers who reported experiencing skin problems,
      16 showed positive results to at least 1 chemical, including 6 cases of multiple
      sensitivity. 2 showed positive reactions to UP base resin, 6 to cobalt chloride,
      5 to benzoyl peroxide (BPO), 4 to methyl ethyl ketone peroxide (MEKPO), 2 to para
      tertiary butyl catechol (PTBC), 1 to styrene and 1 to formaldehyde. After taking
      into account their exposures and reported causes by questionnaires and their
      patch test results, 7 cases were diagnosed as allergic contact dermatitis (ACD)
      due to chemicals, 3 as irritant contact dermatitis (ICD) due to chemicals, and 3
      as dermatitis due to mechanical irritation (MI) from glass fibre or dust, as well
      as 9 as ACD and/or MI. 18 of the total of 29 subjects (62.1%), including 2
      workers without a history of skin problems, were sensitized to at least 1
      chemical. Cobalt, peroxides, PTBC and UP base resin were the common causes of
      ACD.

PMID- 12190623
TI  - UV filters in sunscreen products--a survey.
AB  - The contents of 18 permitted chemical UV filters in 75 sunscreen products have
      been determined to check the compliance of these products with the EU Cosmetic
      Directive, as well as to generate data for quantitative exposure assessments. 81%
      of the products were found to contain 14 of the target chemical UV filters. The
      remaining products contained only the physical UV-filters titanium oxide and zinc
      oxide, which were not determined in the present study. Maximum content (29.3%) of
      chemical UV filters was found in a product that contained 6 of the target UV
      filters. Octyl methoxycinnamate (1.4-4.7%) and butyl methoxydibenzoylmethane (0.4
      4.8%) were the most frequently used UV filters, present, respectively, in 49% and
      44% of the investigated products. Correlation between declared sun protection
      factor (SPF) and the contents of chemical UV filters in the respective products
      was not significant (correlation coefficient 0.5362). The content of UV filters
      in all products complied with the maximum allowed concentration of these
      according to EU Cosmetic Directive.

PMID- 12190624
TI  - Reproducible identification of the causative drug of a fixed drug eruption by
      oral provocation and lesional patch testing.

PMID- 12190625
TI  - A new case of pseudophytodermatitis: allergic contact dermatitis from nickel in
      an ornamental plant (Euphorbia triangularis).

PMID- 12190626
TI  - Nummular lichenoid dermatitis from mercury dental amalgam.

PMID- 12190627
TI  - Contact dermatitis from Vernonia noveboracensis.

PMID- 12190628
TI  - Delayed-type hypersensitivity reaction to ethambutol and isoniazid.

PMID- 12190629
TI  - Allergic contact otitis externa due to iodoform in BIPP cavity dressings.

PMID- 12190630
TI  - Type I and Type IV sensitization to Anisakis simplex in 2 patients with hand
      eczema.

PMID- 12190631
TI  - Occupational allergic contact dermatitis from epoxy resin systems and possibly
      acetone in a shoemaker.

PMID- 12190632
TI  - Allergic contact dermatitis from thiurams with pemphigus-like autoantibodies.

PMID- 12190633
TI  - Allergic contact cheilitis due to carvone in toothpastes.

PMID- 12190634
TI  - Hair loss.

PMID- 12190635
TI  - Assessment of hair loss: clinical relevance of hair growth evaluation methods.
AB  - This review on hair growth measurement methods focuses on human scalp hair in the
      context of clinically relevant assessment of hair loss. This phenomenon is the
      end result of a complex combination of events closely associated with hair
      cycling followed by defective hair replacement. The methodological spectrum
      ranges from the most to the least invasive approach. All of the measurement
      methods referred to are critically reviewed, with their stronger and weaker
      aspects, in view of their potential application in the skin and hair clinic. The
      existence of recently developed highly resolutive noninvasive analytical methods
      capable of exploring almost every aspect of the dynamics of this growth and loss
      phenomenon allowed calibration of more global scoring method. From this review,
      the author concludes that a combination of a highly resolutive analytical
      approach with a global calibrated method seems advisable in the context of the
      monitoring of hair growth changes for better or worse, i.e. scalp hair growth or
      hair loss in the hair clinic.

PMID- 12190636
TI  - Clinical relevance of hair microscopy in alopecia.
AB  - Hair microscopy can clarify the cause of hair loss in a range of diagnoses. Most
      of these are associated with hair breakage, the rest are related to lack of
      growth. Hair breakage may be due to excessive trauma or underlying
      susceptibility, where structural clues may be present. Lack of growth reflects
      follicular dynamics and represents the central mechanism of most common causes of
      alopecia. In such conditions, microscopy only reveals nonspecific confirmation of
      short anagen. Although this may assist clinical diagnosis, microscopy in alopecia
      only allows exclusion of diagnoses related to hair breakage. Confidence in the
      outcome of hair microscopy is based on the size of the sample of hairs, the
      length of the hair, the characteristics of the observations and the experience of
      the person undertaking the microscopy.

PMID- 12190637
TI  - Male androgenetic alopecia.
AB  - Androgenetic alopecia (AGA) is the most common type of hair loss in men. The
      relative strong concordance of the degree of baldness in fathers and sons is not
      consistent with a smiple Mendelian trait and a polygenic basis is considered to
      be most likely. So far the predisposing genes for AGA are unknown and we do not
      understand the molecular steps involved in androgen-dependent beard growth versus
      androgen-dependent hair loss, but AGA can be defined as a DHT-dependent process
      with continuous miniaturization of sensitive hair follicles. The type 2 5aR plays
      a central role by the intrafollicular conversion of T to DHT. Due to the
      inceasing knowledge in this field, this article shall privide an critical
      overwiew of recent discoveries.

PMID- 12190638
TI  - Female pattern hair loss.
AB  - Female pattern hair loss is a common condition characterized by a diffuse
      reduction in hair density over the crown and frontal scalp with retention of the
      frontal hairline. The prevalence increases with advancing age. It has been widely
      thought to be the female counterpart of male balding and is often referred to as
      female androgenetic alopecia. However, the role of androgens is not fully
      established. Scalp hair loss is undoubtedly a feature of hyperandrogenism in
      women but many women with female pattern hair loss have no other clinical or
      biochemical evidence of androgen excess. Female pattern hair loss is probably a
      multifactorial genetically determined trait and it is possible that both androgen
      dependent and androgen-independent mechanisms contribute to the phenotype. In
      managing patients with female pattern hair loss the physician should be aware
      that the adverse effects on quality of life can be quite severe and do not
      necessarily correlate with the objective degree of hair loss. The treatment
      options are currently limited but modest improvements in hair density are
      achievable in some women.

PMID- 12190639
TI  - Telogen effluvium.
AB  - The term telogen effluvium, first coined by Kligman in 1961, refers to the loss
      of club (telogen) hair in disease states of the follicle. Kligman's hypothesis
      was that whatever the cause of hair loss, the follicle tends to behave in a
      similar way, namely the premature termination of anagen. "The follicle is
      precipitated into catagen and transforms into a resting stage that mimics
      telogen." Ipso facto the observation of telogen hair loss does not infer a cause.
      To establish the cause of the hair loss, one requires a history to identify known
      triggers, biochemical investigations to exclude endocrine, nutritional or
      autoimmune aetiologies and in many cases histology to identify the earliest
      stages of androgenetic alopecia. The duration of the hair loss at presentation
      helps predict those patients in whom further investigation will have the greatest
      yield. "It is unfortunate that baldness has been approached with an eye toward
      "regrowing" or "restoring hair", and thus with a tendency toward commercialism.
      Locked within the metamorphosing hair follicles in the balding scalp are all the
      secrets of growth and differentation. Searching for these secrets should
      transcend the eagerness to "regrow" hair on a bald scalp, an achievement which is
      of no great consequence. When we know these answers, we shall have the key, not
      to hair growth alone, but to all growth, which is, after all, the basis of all
      biological phenomena." William Montagna, 1959.

PMID- 12190640
TI  - Nutritional factors and hair loss.
AB  - The literature reveals what little is known about nutritional factors and hair
      loss. What we do know emanates from studies in protein-energy malnutrition,
      starvation, and eating disorders. In otherwise healthy individuals, nutritional
      factors appear to play a role in subjects with persistent increased hair
      shedding. Hard, 40 years ago, demonstrated the importance of iron supplements in
      nonanaemic, iron-deficient women with hair loss. Serum ferritin concentrations
      provide a good assessment of an individual's iron status. Rushton et al. first
      published data showing that serum ferritin concentrations were a factor in female
      hair loss and, 10 years later, Kantor et al. confirmed this association. What
      level of serum ferritin to employ in subjects with increased hair shedding is yet
      to be definitively established but 70 micro g/L, with a normal erythrocyte
      sedimentation rate (< 10 mm/h), is recommended. The role of the essential amino
      acid, l-lysine in hair loss also appears to be important. Double-blind data
      confirmed the findings of an open study in women with increased hair shedding,
      where a significant proportion responded to l-lysine and iron therapy. There is
      no evidence to support the popular view that low serum zinc concentrations cause
      hair loss. Excessive intakes of nutritional supplements may actually cause hair
      loss and are not recommended in the absence of a proven deficiency. While
      nutritional factors affect the hair directly, one should not forget that they
      also affect the skin. In the management of subjects with hair loss, eliminating
      scaling problems is important as is good hair care advice and the need to explain
      fully the hair cycle. Many individuals reduced their shampooing frequency due to
      fear of losing more hair but this increases the amount seen in subsequent
      shampoos fuelling their fear of going bald and adversely affecting their quality
      of life.

PMID- 12190641
TI  - Epidemiology and genetics of alopecia areata.
AB  - The frequency of alopecia areata and observed patterns of heritability are in
      keeping with a polygenic inheritance model but the genetics of alopecia areata is
      still poorly understood. The role of environmental factors in triggering disease
      initiation or exacerbation remains almost entirely speculative. Using the
      candidate gene approach, three susceptibility/severity factors have been
      identified. HLA alleles were the first to show a strong association with alopecia
      areata and some DQB and DR alleles have been demonstrated to confer a high risk
      for disease by both case-control and family-based studies. Interleukin (IL)-1
      cluster genes, mainly the IL-1 receptor antagonist, show a strong association
      with disease severity in alopecia areata and a number of other autoimmune and
      inflammatory diseases. Finally, the association of alopecia areata with Down's
      syndrome, the high frequency of alopecia areata in autoimmune polyglandular
      syndrome type I due to mutations of the autoimmune regulator (AIRE) gene on
      chromosome 21q22.3 and the finding of association with MX1, another gene in the
      Down's syndrome region of chromosome 21 indicate this area of the genome as a
      promising target for future-family based investigations. The role of individual
      genes of the MHC, IL-1 cluster or chromosome 21q22.3 is difficult to establish
      and further genetic and functional investigations are needed to confirm their
      involvement in the pathogenesis of alopecia areata.

PMID- 12190642
TI  - Alopecia areata - animal models.
AB  - Several rodent models with spontaneous and induced alopecia areata (AA), a
      nonscarring inflammatory hair loss disease with suspected autoimmune elements,
      have been identified. Of these, the C3H/HeJ mouse and DEBR rat have been most
      extensively used in examining AA development. Flow cytometry and micro array
      characterization, manipulation of inflammatory cells by in vivo cell depletion or
      cell receptor blockade, lymph node cell transfer between affected and unaffected
      rodents, and the recent use of transgenic knockout mice have given important
      insights into the development of AA. From our current understanding of rodent
      models, the development of AA relies upon a general genetic susceptibility where
      major susceptibility genes may be supplemented by minor disease severity
      modifying genes. However, the actual onset of AA, its duration, extent, and
      persistence in individual rodents may be modified by epigenetic factors. Rodent
      AA seems to be fundamentally, but not exclusively, Th1 cell mediated. Onset of
      disease may be dependent on several factors including the break down of the
      putative anagen stage hair follicle immune privilege, appropriate antigen
      presentation with costimulation of lymphocytes, presence of autoreactive
      lymphocytes, and a deficiency of functional immune system regulatory cells.
      Rodents have already been used in examining a variety of current AA treatments
      and developing new therapies with some success. With a greater understanding of
      AA disease mechanisms through rodent model research, improved and more specific
      treatment interventions may be defined.

PMID- 12190643
TI  - Cosmetics and hair loss.
AB  - Cosmetic hair care products are often implicated by the user or the clinician in
      cases of hair loss. Yet, these products are used ad lib, in a wide variety of
      home conditions and on a wide variety of hair types, by millions of consumers
      every day with no adverse effects. Based on this extensive data set, the absence
      of literature reports, and a detailed understanding of the mode of action of
      cosmetic hair care products, we can conclude that they do not cause hair loss.
      Clinicians investigating cases of hair loss must fully appreciate the hair cycle,
      the length of time a single fibre may be present on the head, and its biological
      and cosmetic history in order to understand the causes of hair loss and make the
      correct diagnosis. With a better understanding of the cosmetic practices used by
      everyday consumers, the clinician will be in a strong position to help patients
      re-grow their hair and guide them through a high quality hair care regime.

PMID- 12190644
TI  - The role of the trichologist.
AB  - The author seeks to establish both the specialty of clinincal trichology and its
      holistic nature. The myth that trichology is either an alternative therapy or a
      complimentary therapy is strongly refuted. Comparisons are drawn between the
      level of service which the trichologist can provide and that which is usually
      available through traditional medical channels. The training of trichologists is
      discussed in outline and its strong scientific base is emphasized. Whilst
      admitting that the majority of trichologists are not medically qualified, the
      author stresses that trichologists are taught medicine within the limits adequate
      for professional discharge of their restricted but specialized role. The article
      concludes by identifying a need for both the public and medical profession to
      learn how to differentiate between the properly trained and qualified
      trichologist and the many unqualified charlatans who monopolize publicity and
      proliferate in the high street. There would appear to be a clear case for better
      understanding of the profession and what it has to offer.

PMID- 12190645
TI  - Feather bedding and allergic disease in children: a cover story?

PMID- 12190646
TI  - Airway goblet cell hyperplasia in asthma: hypersecretory and anti-inflammatory?

PMID- 12190647
TI  - Mycobacterium-based vaccines for the prevention of allergic disease: a progress
      report.

PMID- 12190648
TI  - Report on the potential allergenicity of genetically modified organisms and their
      products.

PMID- 12190649
TI  - Asthma, nasal polyposis and ulcerative colitis: a new perspective.

PMID- 12190650
TI  - The use of a feather quilt, childhood asthma and allergic rhinitis: a prospective
      cohort study.
AB  - BACKGROUND: Feather bedding has long been considered as a potential source of
      allergen exposure and thus a potential risk factor for allergic diseases.
      However, recent cross-sectional studies have reported a higher risk of allergic
      diseases among users of synthetic bedding compared with feather-bedding users.
      OBJECTIVE: To explore associations between early life exposure to feather bedding
      and the risk of developing asthma allergic rhinitis in childhood. METHODS: We
      assessed the association between early life exposure to feather quilts and the
      risk of bronchial obstruction during the first 2 years of life and asthma and
      allergic rhinitis in a prospective 4-year cohort study of 2531 Norwegian
      children. RESULTS: At the age of 6 months, 24% of the children had a quilt with
      feathers, decreasing to 20% at the age of 2 years. The adjusted odds ratio for
      bronchial obstruction 0 to 2 years by exposure to a feather quilt at the age of 6
      months was 0.59, 95% confidence interval 0.41 to 0.86, for asthma at the age of 4
      years 0.38, 0.23 to 0.64 and for allergic rhinitis at the age of 4 years 0.73,
      0.43 to 1.18. CONCLUSION: The use of a feather quilt in early life does not seem
      to increase the risk of asthma and allergic rhinitis later in childhood.

PMID- 12190651
TI  - Parental farming protects children against atopy: longitudinal evidence involving
      skin prick tests.
AB  - BACKGROUND: There is growing evidence that the development of allergic
      sensitization can be influenced by environmental co-factors. Studies showed that
      growing up on a farm can protect children against allergic sensitization.
      However, little is known whether this 'farming effect' can only be observed in
      early lifetime or whether it also plays a role in later childhood. OBJECTIVE: The
      aim of our study was to test whether a farming environment is negatively
      associated with a new occurrence of skin prick test (SPT) positivity in school
      children. As a secondary outcome we investigated whether children living on a
      farm lose their allergic sensitization more frequently than other children.
      METHODS: In a longitudinal design, 1150 elementary school children (mean age 7.8
      years, SD 0.7) were recruited from nine different areas of Austria in 1994. A
      questionnaire and an SPT involving seven common aero-allergens were performed at
      study entry and at follow-up 3 years later. RESULTS: A total of 844 children, who
      underwent two SPTs, were included in the analyses; 15.1% of their families
      reported working on a farm. Adjusting for potential confounders (parental
      education, number of siblings, sex, family history of allergy), parental farming
      was inversely related to the prevalence and new occurrence of SPT positivity [no
      farming 12.2%, part-time farming 6%, full-time farming 2.2% incidence; odds ratio
      (OR) farming vs. non-farming 0.34, 95% confidence interval (CI) 0.12-0.98].
      Furthermore, children living in a farming environment were more likely to lose
      their SPT positivity during follow-up (no farming 14.6%, part-time farming 50%,
      full-time farming 60% loss of sensitization; OR farming vs. non-farming 8.06; 95%
      CI 2.05-31.75). No difference in the pattern of sensitization to specific
      allergens could be observed between farming and non-farming children. CONCLUSION:
      A farming environment has a strong negative effect on the development of allergic
      sensitization. Furthermore, the study provides evidence that atopic children
      living on a farm lose their SPT positivity more frequently than children from non
      farming environments.

PMID- 12190652
TI  - Prevalence and severity of allergic rhinitis in house dust mite-allergic patients
      with bronchial asthma or atopic dermatitis.
AB  - BACKGROUND: Allergic rhinitis, asthma and atopic dermatitis are closely
      associated. Although population-based studies report a high prevalence of
      rhinitis among asthma patients, less is known of the association between rhinitis
      and atopic dermatitis and the severity of concomitant rhinitis. OBJECTIVES: We
      aimed to determine the prevalence and severity of allergic rhinitis among
      asthmatics and patients with atopic dermatitis and assessed whether age and
      comorbidity influence the severity of rhinitis signs and symptoms. METHODS: Three
      hundred and twenty-five patients recruited for a multicentre trial to study the
      effect of encasings of mattresses, pillows and duvets on signs and symptoms of
      allergic rhinitis and/or asthma and/or atopic dermatitis recorded visual analogue
      scores (VAS) and daily symptom scores and underwent nasal challenge tests with
      house dust mite (HDM). RESULTS: Based on history and clinical symptoms 92% of the
      164 asthmatic patients and 85% of the 86 patients with atopic dermatitis could be
      diagnosed as having rhinitis. Inclusion of a positive provocation to HDM did not
      result in a substantial lower prevalence of rhinitis. Subjects reported moderate
      symptoms, with mean rhinitis VAS scores ranging from 40.0 to 55.0. Presence of
      atopic dermatitis was associated with lower rhinitis VAS and symptoms scores,
      whereas in multivariate analysis the presence of asthma was positively associated
      with nasal responsiveness to HDM. CONCLUSION: The prevalence of nasal symptoms in
      patients with bronchial asthma or atopic dermatitis and sensitized to house dust
      mites is high. Although the majority of patients experience mild to moderate
      symptoms, the presence of nasal disease needs to be examined in all patients with
      atopic disorders.

PMID- 12190653
TI  - Particulate masks and non-powdered gloves reduce latex allergen inhaled by
      healthcare workers.
AB  - BACKGROUND: Although allergy to latex is a well-characterized phenomenon, some
      hospitals continue to provide staff with powdered latex gloves as an option to
      low- or non-powdered gloves. OBJECTIVE: We aimed to measure the extent to which
      inhalation of latex particles could be reduced by the use of protective masks or
      by replacing powdered latex gloves with non-powdered latex gloves. METHODS:
      Twenty healthcare workers in a hospital setting wore nasal air samplers (NAS) and
      Institute of Occupational Medicine (IOM) samplers for four 20-min periods.
      Subjects wore powdered gloves, non-powdered gloves and no gloves during three
      sampling periods, and in the fourth, subjects applied an aerosol barrier face
      mask or a particulate face-mask (N95) while wearing powdered gloves. All samples
      were stained for particles bearing Hev b 5 allergen by the Halogen assay.
      RESULTS: All subjects inhaled Hev b 5 bearing particles in all sampling periods.
      IOM samplers collected particles at 70% of the rate of NAS. The number of
      particles inhaled while wearing powdered gloves was 23.8-fold higher than when
      not wearing gloves and 9.7-fold higher than when wearing non-powdered latex
      gloves (P < 0.0001). Wearing an aerosol barrier mask did not significantly reduce
      the number of particles inhaled (P = 0.108), while use of particulate masks
      significantly reduced the number of particles inhaled by 17.4-fold (P = 0.003).
      CONCLUSIONS: Use of non-powdered gloves is the most effective method of reducing
      occupational aeroallergen exposure to latex arising from gloves. However,
      secondary protection using particulate masks is a valid alternative, and may be
      helpful for preventing respiratory sensitization.

PMID- 12190654
TI  - Sensitization to horse hair, symptoms and lung function in grooms.
AB  - OBJECTIVE: This study aimed to investigate the rate of occupational sensitization
      to horse hair in grooms and whether occupational exposure to horse hair increases
      respiratory and allergic symptoms and affects lung function in grooms or not.
      METHODS: This is a cross-sectional study. Two hundred grooms were randomly
      selected among 1000 grooms working in Veliefendi Hippodrome of Istanbul. One
      hundred and twenty-five subjects agreed to enter the study. Ninety-two workers
      who worked in the different parts of this hippodrome enrolled as the control
      group. A detailed questionnaire including respiratory and allergic symptoms was
      filled in, physical examination, skin prick tests and pulmonary function tests
      were performed. RESULTS: Sensitization to horse hair was 12.8% in grooms and 4.3%
      in controls. The difference was statistically significant (P = 0.0035). Asthma
      was found in 14.4% of the grooms and 5.4% of the controls, allergic rhinitis in
      42.4% of the grooms and 18.4% of the controls, allergic conjunctivitis in 35.2%
      of the grooms and 15.2% of the controls, and allergic skin diseases in 32.8% of
      the grooms and 13% of the controls. The differences were statistically
      significant (P = 0.043, P = 0.0002, P = 0.001 and P = 0.0008, respectively). The
      means of FEV1, FEV1/FVC and FVC parameters were significantly lower in the groom
      group (P = 0.006, P = 0.001 and P = 0.003, respectively). In the multivariate
      analysis, being in the groom group and working years were found to be predictive
      factors for impairments of lung function (P < 0.001 and P = 0.002, respectively).
      CONCLUSION: Occupational exposure to horse increases the sensitization to horse
      hair, induces asthma and allergic symptoms and also impairs lung functions.

PMID- 12190655
TI  - Airways hyper-responsiveness to bradykinin and methacholine: effects of inhaled
      fluticasone.
AB  - BACKGROUND: Although inhaled corticosteroids are the most effective anti
      inflammatory agents available for the treatment of asthma, they have, at best,
      only modest effects on airways responsiveness to methacholine. Thus, hyper
      responsiveness to methacholine is a relatively insensitive monitor of the
      effectiveness of glucocorticoids in asthmatic subjects. OBJECTIVE: The study
      aimed to determine if airways hyper-responsiveness to bradykinin provides a more
      sensitive index of glucocorticoid responsiveness in asthmatic subjects than does
      hyper-responsiveness to methacholine. METHODS: A double-blind, placebo
      controlled, parallel group study comparing the effects of inhaled fluticasone
      (220 micro g twice daily) on responsiveness to the two stimuli in asthmatic
      subjects who had never previously received corticosteroid therapy. Drug (n = 13)
      or placebo (n = 12) were administered for 16 weeks. Responsiveness to bradykinin
      and methacholine was determined at baseline and at 4 week intervals. RESULTS:
      Placebo did not alter responsiveness to either stimulus compared to baseline.
      Fluticasone treatment significantly reduced responsiveness to bradykinin (P <
      0.001 by Friedman anova) and methacholine (P = 0.02), but changes in
      responsiveness to bradykinin were significantly greater than those in
      methacholine responsiveness (P = 0.002). Bradykinin responsiveness was decreased
      at all treatment times compared to baseline, while methacholine responsiveness
      was not decreased until 8 weeks of therapy. When data were analyzed as changes
      from baseline (DeltaLog PD20), DeltaLog PD20 for methacholine was not different
      at any time-point between the two treatment groups. By contrast, DeltaLog PD20
      for bradykinin was significantly greater in patients receiving fluticasone
      compared to those on placebo at all but the 16-week treatment time. Ten of 13
      subjects receiving fluticasone failed, on at least one post-treatment visit, to
      show a 20% fall in forced expiratory volume (FEV1), even at the highest dose of
      bradykinin. CONCLUSIONS: Airways responsiveness to bradykinin is more profoundly,
      and more rapidly, reduced by inhaled glucocorticoids than is responsiveness to
      methacholine. Airways hyper-responsiveness to bradykinin provides a convenient
      and sensitive monitor of glucocorticoid responsiveness in asthma.

PMID- 12190656
TI  - Leukotriene receptor antagonist, montelukast, can reduce the need for inhaled
      steroid while maintaining the clinical stability of asthmatic patients.
AB  - BACKGROUND: Oral leukotriene receptor antagonists have been shown to have
      efficacy in chronic asthma. OBJECTIVE: To determine whether the addition of
      montelukast could lead to a reduction in inhaled corticosteroid dose without a
      significant decrease in peak expiratory flow rate (PEFR). METHODS: After a 4-week
      run-in period, 191 moderate-to-severe asthmatic patients whose asthma had been
      well controlled with daily inhaled corticosteroid therapy (beclometasone
      dipropionate 800 to 1600 micro g/day), were randomly assigned to one of two
      treatments - placebo (n = 98) or montelukast 10 mg once daily (n = 93) - for a 24
      week, multicentre, double-blind, treatment period. At the beginning of the active
      treatment period, the daily dose of inhaled corticosteroid was halved in all of
      the patients. In addition, the inhaled corticosteroid dose was subsequently
      titrated every 8 weeks, based on PEFR, asthma symptoms and beta-agonist use.
      RESULTS: After 8 weeks of a 50% reduction in inhaled corticosteroid use, morning
      PEFR increased by 5.3 +/- 32.3 L/min from baseline in patients receiving
      montelukast and significantly decreased by 6.9 +/- 29.0 L/min in those receiving
      placebo (P = 0.035). In addition, evening PEFR significantly decreased by 9.8 +/-
      28.5 L/min (P = 0.003) in the placebo group, but was maintained in the
      montelukast group. In spite of a subsequent 50% reduction in the inhaled
      corticosteroid dose every 8 weeks, morning and evening PEFRs were maintained over
      the 24-week treatment period in the montelukast group; PEFR significantly
      decreased in the placebo group. There was a significant difference between the
      two groups with regard to morning PEFR, therapy score and asthmatic score at
      weeks 8, 16 and 24, as well as evening PEFR at week 8. However, the symptom
      scores were not significantly different between the two groups or within each
      group. CONCLUSION: These data suggest that montelukast reduces the need for
      inhaled corticosteroids while maintaining asthma control over a 24-week period.
      Therefore, montelukast may be useful for long-term treatment in patients with
      asthma who require high doses of inhaled corticosteroids.

PMID- 12190657
TI  - Cetirizine and levocetirizine inhibit eotaxin-induced eosinophil transendothelial
      migration through human dermal or lung microvascular endothelial cells.
AB  - BACKGROUND: Several second-generation antihistamines have documented anti
      inflammatory effects which appear independent of H1-receptor blockade. We
      investigated the inhibitory effect of cetirizine and its active enantiomer
      levocetirizine on eosinophil transendothelial migration (TEM) through monolayers
      of normal human dermal microvascular endothelial cells (HMVEC-d) or human lung
      microvascular endothelial cells (HMVEC-l). METHODS: HMVEC-d or HMVEC-l were grown
      to confluence on micropore filters in transwells inserted into a 24-well tissue
      culture dish. Eosinophils were isolated by density gradient centrifugation and
      negative immunomagnetic selection. Untreated eosinophils or eosinophils pre
      incubated (30 min at 37 degrees C) with a concentration range of cetirizine or
      levocetirizine (10-5 to 10-9 m) were added to the upper chamber of the transwell
      which was incubated for 60 min at 37 degrees C. Both spontaneous eosinophil TEM
      and TEM to 100 ng/mL of human eotaxin in the lower chamber were assessed.
      RESULTS: Between 8 and 10% of the eosinophils added to the upper chamber
      underwent spontaneous TEM through HMVEC-d or HMVEC-l. The addition of eotaxin to
      the lower chamber enhanced eosinophil TEM through HMVEC-d or HMVEC-l monolayers
      to over 20%, i.e. an enhanced TEM of approximately 100% in each case. Pre
      incubation of eosinophils with cetirizine or levocetirizine dose-dependently
      inhibited eosinophil TEM to eotaxin through both HMVEC-d or HMVEC-l with total
      inhibition of eotaxin-induced TEM observed at 10-8 m for HMVEC-d and 10-7 m for
      HMVEC-l. Both drugs gave a reduced but significant inhibition of eosinophil TEM
      at lower concentrations. No concentration of cetirizine or levocetirizine had any
      significant effect on expression of CD11b, CD18 or CD49d by either resting or
      eotaxin-stimulated eosinophils. Furthermore, no effect on spontaneous eosinophil
      TEM, or eosinophil viability was seen with any concentration of cetirizine or
      levocetirizine. CONCLUSION: Levocetirizine inhibits eotaxin-induced eosinophil
      TEM through both dermal and lung microvascular endothelial cells suggesting that,
      like cetirizine, levocetirizine has potential anti-inflammatory effects.

PMID- 12190658
TI  - Prevalence of endothelial nitric oxide synthase gene polymorphisms in patients
      with atopic asthma.
AB  - BACKGROUND: Asthma is a common multifactorial disease, the aetiology of which is
      attributable to both environmental and genetic factors. The endothelial nitric
      oxide synthase (NOS3) gene has been implicated in asthma pathogenesis. OBJECTIVE:
      This study investigated associations of 27 base-pair tandem repeat polymorphism
      in intron 4 and the Glu298Asp (G894T) variant of the NOS3 gene with atopic asthma
      in a Czech population. METHODS: Polymerase chain reaction was used to determine
      the NOS3 genotypes in subjects with atopic asthma (n = 163) and random controls
      (n = 209). RESULTS: The NOS3 allele or genotype distributions did not differ
      significantly between the control and asthma groups. However, the common genotype
      (bb) of the NOS3 polymorphism in intron 4 was found to be significantly
      associated with total IgE levels (P = 0.006), specific IgE levels for feathers (P
      = 0.0002) and a positive skin prick test for hay (P = 0.004). In one atopic
      patient, we identified an additional 27-bp repeat in the NOS3 gene (NOS3c), which
      occurred in heterozygous combination with the NOS3b allele (NOS3b/c genotype). In
      addition, we describe a new polymorphism (A5495G) in the NOS3 gene, which was in
      almost complete linkage disequilibrium with the NOS3 repeat polymorphism in
      intron 4. The Glu298Asp variant was not associated with asthma and/or related
      atopic phenotypes in our study. CONCLUSION: Neither the NOS3 'b' allele nor the
      NOS3 'b/b' genotype showed any general association with atopic asthma, but they
      were associated with atopy-related phenotypes. We conclude that the NOS3 gene
      polymorphisms may act as disease modifiers in atopic asthma phenotype in our
      population.

PMID- 12190659
TI  - Analysis of association and linkage for the interleukin-4 and interleukin-4
      receptor b;alpha; regions in Swedish atopic dermatitis families.
AB  - BACKGROUND: Atopic dermatitis (AD) is caused by genetic and environmental factors
      that interact to determine disease susceptibility and severity. Several lines of
      evidence suggest that the IL-4 gene and the IL-4-receptor alpha (IL-4Ralpha) gene
      are involved in the development of atopic diseases. OBJECTIVE: The objective of
      this study was to evaluate the possible involvement of the chromosomal regions
      5q31 and 16p12, which include the genes coding for the IL-4 and the IL-4Ralpha in
      AD. METHODS: We conducted linkage analysis and association studies using the
      microsatellite markers D16S298 and D16S403 and a single nucleotide polymorphism
      in the promoter region of the IL-4 gene (- 590C/T) in 406 Swedish families with
      at least two siblings affected with AD, in total 1514 individuals. RESULTS AND
      CONCLUSION: We report linkage (P < 0.005) to the - 590C/T polymorphism in the
      promoter of the IL-4 gene for the semiquantitative trait severity score of AD.
      Neither linkage nor association was found to the IL-4Ralpha chromosomal region.

PMID- 12190660
TI  - Identification of shared and unique immunoglobulin E epitopes of the highly
      conserved tropomyosins in Blomia tropicalis and Dermatophagoides pteronyssinus.
AB  - BACKGROUND: Tropomyosin belongs to a class of highly conserved proteins in
      invertebrates and vertebrates. The invertebrate tropomyosins are allergenic in
      man with high IgE cross-reactivity and have been therefore referred to as pan
      allergens. OBJECTIVES: This study aimed to clone and identify the IgE epitopes of
      tropomyosin from Blomia tropicalis (Blo t 10) mite. Cross-reactivity between the
      IgE epitopes of Blo t 10 and Der p 10 was also evaluated. METHODS: Blo t 10 was
      isolated using mouse anti-Der p 10 antibodies. Allergenicity of the cloned Blo t
      10 was confirmed by skin prick test (SPT) and enzyme-linked immunosorbent assay
      (ELISA). Dose-dependent inhibition assay was performed to determine the degree of
      IgE cross-reactivity between Blo t 10 and Der p 10. Overlapping polymerase chain
      reaction-derived cDNA were generated and expressed as glutathione-S-transferase
      (GST) recombinant proteins in Escherichia coli and used to identify shared and
      unique IgE epitopes of Blo t 10 and Der p 10. RESULTS: The cloned Blo t 10 shared
      up to 96% amino acid identity to tropomyosin of other mites. SPT and ELISA IgE
      immunoassay showed recombinant Blo t 10 sensitization rates of between 20% and
      29% in atopic subjects. Results of SPT and dose-dependent inhibition assays
      showed that some allergic individuals had unique IgE epitopes for Blo t 10. IgE
      epitope mapping of Blo t 10 revealed that the epitopes were mainly located at N-
      and C-termini of the molecule. The results of ELISA inhibition assays of
      overlapping recombinant fragments indicated that the unique IgE epitopes of Blo t
      10 were located at the C-terminal. CONCLUSION: Although Blo t 10 and Der p 10 are
      highly conserved (shared 95% amino acids identity) and significantly cross
      reactive, unique IgE epitopes do exist. The results suggest the potential
      deficiency of using only one of these highly conserved allergens as diagnostic or
      therapeutic reagents.

PMID- 12190661
TI  - Allergenicity of some isoforms of white sesame proteins.
AB  - BACKGROUND: Allergy to sesame seeds is often associated with particularly severe
      reactions, with a high risk of anaphylaxis. The increase in reports of allergic
      reactions to sesame is probably due to the growing use of sesame seeds or sesame
      oil in food. OBJECTIVE: To determine the molecular weights of the proteins in
      three variety of sesame seeds and to study the isoelectric points and the
      allergenicity of white sesame proteins. METHODS: Extracts of white, brown and
      black sesame seeds were prepared. The white sesame extract, mostly used in
      bakery, was run on SDS-PAGE and two dimensional electrophoresis. Six sera from
      patients sensitized or symptomatic to sesame seed were used for Western blotting.
      RESULTS: The protein patterns of the white, brown and black sesame extracts
      showed major quantitative differences. The white extract had the higher protein
      concentration and contained 15 proteins of 12-79 kDa, some of them having several
      acidic isoelectric points. The lowest isoelectric point was 4.9 and the highest
      was 6.4, giving 35 isoforms. Ten of the 15 proteins (12-57.5 kDa) were recognized
      by specific IgE. The 12-13 kDa and 22-33 kDa proteins could correspond to the
      main allergens. CONCLUSION: White sesame seeds contain at least 10 allergenic
      proteins with acidic isoelectric points. In accordance with previous results, two
      of them seem to contain the major allergens.

PMID- 12190662
TI  - Allergy after ingestion or inhalation of cereals involves similar allergens in
      different ages.
AB  - BACKGROUND: Cereals are among the major foods that account for food
      hypersensitivity reactions. Salt-soluble proteins appear to be the most important
      allergens contributing to the asthmatic response. In contrast, very limited
      information is available regarding cereal allergens responsible for allergic
      reactions after ingestion of cereal proteins. OBJECTIVE: The aim of this study
      was to evaluate the allergenic reactivity of ingested and inhaled cereal
      allergens in different ages, in order to investigate if the response to different
      allergens would depend on the sensitization route. METHODS: We included 66
      patients in three groups. Group 1: 40 children aged 3 to 6 months who suffered
      from diarrhoea, vomiting, eczema or weight loss after the introduction of cereal
      formula in their diet and in which a possibility of coeliac disease was
      discarded. Group 2: 18 adults with food allergy due to cereals tested by prick
      tests, specific IgE and food challenge. Group 3: eight patients previously
      diagnosed as having baker's asthma. Sera pool samples were collected from each
      group of patients and IgE immunoblotting was performed. RESULTS: We found an
      important sensitization to cereal in the 40 children. The most important
      allergens were wheat followed by barley and rye. Among the adults with cereal
      allergy, sensitization to other allergens was common, especially to Lolium
      perenne (rye grass) pollen. Immunoblotting showed similar allergenic detection in
      the three groups. CONCLUSION: Clinically significant reactivity to cereal may be
      observed in early life. Inhalation and ingestion routes causing cereal allergy
      seem to involve similar allergens. The diet control was more effective in
      children. The possibility of cereal allergy after the introduction of cereal
      formula during the lactation period should not be underestimated.

PMID- 12190663
TI  - The correlation between ovomucoid-derived peptides, human leucocyte antigen class
      II molecules and T cell receptor-complementarity determining region 3
      compositions in patients with egg-white allergy.
AB  - BACKGROUND: Food allergies are more prevalent in children, due to the immature
      gastrointestinal epithelial membrane barrier allowing more proteins through the
      barrier and into circulation. Ovomucoid (OM) is one of the major allergens that
      is found in egg white. OBJECTIVE: The aim of this study was to determine T cell
      epitopes, antigen-presenting human leucocyte antigen (HLA) class II molecules of
      the T cell lines (TCLs) and T cell clones (TCCs), and complementarity determining
      region (CDR) 3 loops of the T cell receptor (TCR) alpha and beta chains of the
      TCCs specific to OM. METHODS: We established TCLs and TCCs specific to OM from
      peripheral blood mononuclear cells (PBMCs) of four atopic patients with egg-white
      allergy using a mixture of a panel of overlapping synthetic peptides
      corresponding to the amino acid sequence of the entire OM. We identified the T
      cell epitopes by antigen-induced proliferative responses, antigen-presenting
      molecules using allogeneic PBMCs and CDR3 loops of the TCR alpha and beta chains
      by cloning and sequence analysis. RESULTS: The TCLs and TCCs responded to seven
      different peptides, and their antigen-presenting molecules were different from
      each other. Sequence analysis of the TCR alpha and beta gene usage of the TCCs
      showed marked heterogeneity, and the usage of the CDR3 loop of the TCCs involved
      heterogenous amino acid residues. Interestingly, TCCs 'IH3.3' and 'YT6.1'
      recognized the same OM peptides, and had the same TCR Vbeta-Jbeta gene usage.
      Considering that peptide motifs bind to HLA class II molecules, the electrically
      charged residue (positive or negative) on the CDR3alpha and the CDR3beta loops of
      TCR of TCC may form ionic bonds with a charged residue on the HLA class II
      molecules-peptide complex. CONCLUSIONS: TCCs that have the same TCR gene usage
      were established from patients who had shown similar hypersensitivity-type,
      indicating that antigen recognition by a specific TCR is closely associated with
      the characteristics of each patient's symptoms.

PMID- 12190664
TI  - Ethanol as a cause of hypersensitivity reactions to alcoholic beverages.
AB  - BACKGROUND: Adverse reactions after ingestion of alcoholic beverages are common.
      Metabolic differences in individuals and also the histamine content in alcoholic
      beverages have been implicated. By contrast pure ethanol has rarely been reported
      as a cause of hypersensitivity reactions and its mechanism has not been clarified
      yet. OBJECTIVE: To determine whether ethanol itself accounts for alcohol
      hypersensitivity in patients with anaphylactic reactions after alcohol intake. In
      search of possible pathomechanisms all patients were analysed by skin prick
      testing and sulfidoleukotriene production of peripheral leucocytes using ethanol
      and its metabolites. METHODS: Double-blind, placebo-controlled food challenges
      with a cumulated amount of 30 mL ethanol were performed in 12 adult patients with
      a positive history of adverse reactions after consumption of different alcoholic
      beverages. Skin prick tests and measurement of sulfidoleukotriene production were
      performed using different concentrations of ethanol and acetaldehyde from 50 to
      1000 mm. RESULTS: Oral challenges with pure ethanol were positive in six out of
      eleven patients. All challenge-positive patients, but also four out of five
      challenge-negative patients, showed an increased sulfidoleukotriene production in
      vitro compared with healthy controls. Skin prick tests using alcoholic beverages,
      ethanol, acetaldehyde and acetic acid were negative in all patients (12/12).
      CONCLUSION: Our study shows that ethanol itself is a common causative factor in
      hypersensitivity reactions to alcoholic beverages. These reactions occur dose
      dependent and a non-IgE-mediated pathomechanism is likely, because skin prick
      tests were negative in all cases. Increased sulfidoleukotriene production was
      determined in some patients, but is no reliable predictor. Therefore oral
      provocation tests remain indispensable in making the diagnosis of ethanol
      hypersensitivity.

PMID- 12190665
TI  - Characterization of chemokine receptor expression and cytokine production in
      circulating CD4+ T cells from patients with atopic dermatitis: up-regulation of C
      C chemokine receptor 4 in atopic dermatitis.
AB  - BACKGROUND: Th2 and Th1 cells have been suggested to express CCR3/CCR4 and
      CCR5/CXCR3, respectively. OBJECTIVE: We examined CCR3, CCR4, CCR5 and CXCR3
      expression and cytokine production in peripheral blood CD4+ T cells from patients
      with atopic dermatitis (AD), which has been postulated to be a Th2-type cell
      mediated disease, and then analysed the possible correlation between these values
      and the levels of several clinical parameters. METHODS: Intracellular cytokine
      production and chemokine receptor expression in peripheral blood CD4+ T cells
      from 40 AD patients and 20 sex- and age-matched healthy control subjects were
      studied by flow cytometry. RESULTS: The frequencies of IL-4- and IL-13-producing
      CD4+ T cells from patients with AD were significantly higher than those from
      healthy control subjects (IL-4:3.9 +/- 2.1% vs. 1.6 +/- 0.7%, P = 0.0005, IL
      13:4.0 +/- 2.1% vs. 1.8 +/- 0.8%, P = 0.0023), whereas the frequencies of IL-2-
      and IFN-gamma-producing CD4+ T cells were significantly decreased in AD patients
      (IL-2:38.1 +/- 10.3% vs. 51.3 +/- 6.3%, P = 0.0003, IFN-gamma: 9.9 +/- 3.5% vs.
      26.4 +/- 4.6%, P < 0.0001). The percentage of CCR4+ cells in CD4+ CD45RO+ T cells
      in AD patients was significantly higher than that in healthy control subjects
      (24.4 +/- 8.0% vs. 10.9 +/- 2.3%, P < 0.0001) and was correlated positively with
      the total serum IgE, serum lactic dehydrogenase (LDH) level, eosinophil number,
      eruption score, and IL-4 and IL-13 secretion in CD4+ T cells, and inversely with
      IL-2 and IFN-gamma secretion in CD4+ T cells. In contrast, CCR3 was not detected
      on circulating CD4+ T cells even in AD patients. On the other hand, the
      percentage of CCR5+ or CXCR3+ cells in CD4+ CD45RO+ T cells in AD patients was
      significantly decreased (CCR5:23.2 +/- 7.0% vs. 28.4 +/- 5.4%, P = 0.023,
      CXCR3:29.9 +/- 11.4% vs. 38.5 +/- 6.7%, P = 0.028) and was positively correlated
      with eruption score (P < 0.05). Multiple regression analyses showed that the
      percentage of CCR4 expression highly correlated with serum IgE, LDH, eosinophil
      number and eruption in AD patients. CONCLUSION: CCR4+ cells might be involved in
      the aetiopathogenesis of AD.

PMID- 12190666
TI  - The skin fungus-induced Th1- and Th2-related cytokine, chemokine and
      prostaglandin E2 production in peripheral blood mononuclear cells from patients
      with atopic dermatitis and psoriasis vulgaris.
AB  - BACKGROUND: It is suggested that skin fungi may be involved in the development of
      atopic dermatitis (AD) and psoriasis vulgaris (PV). OBJECTIVE: We studied skin
      fungus-induced Th1- or Th2-related cytokine, chemokine and prostaglandin E2
      (PGE2) secretion in peripheral blood mononuclear cells (PBMC) from patients with
      AD and PV and normal subjects. METHODS: PBMC were cultured with the extracts of
      Malassezia furfur (MF), Candida albicans (CA) and Trichophyton rubrum (TR). The
      cytokine, chemokine and PGE2 amounts in the supernatants were measured by enzyme
      linked immunosorbent assays. RESULTS: MF induced IL-4 and macrophage-derived
      chemokine (MDC) secretion in AD patients, while induced IFN-gamma and interferon
      inducible protein of 10 kDa (IP-10) secretion in PV patients, however, did not
      induce either secretion in normal subjects. CA induced IL-4, MDC, IFN-gamma and
      IP-10 secretion in AD and PV patients and normal subjects. In AD patients, the
      magnitude of IL-4 and MDC responses to CA was higher than that to MF. Compared
      with PV patients and normal subjects, the magnitude of IL-4 and MDC responses to
      CA was higher while that of IFN-gamma and IP-10 responses to CA was lower in AD
      patients. TR induced moderate IL-4 and MDC secretion only in AD patients. The
      three fungi induced higher levels of PGE2 secretion in AD patients than in PV
      patients and normal subjects. Cyclooxygenase-2 inhibitor NS-398 suppressed PGE2
      responses to MF, CA and TR, and partially suppressed IL-4 and MDC responses to
      MF, CA and TR, while enhanced IFN-gamma and IP-10 responses to CA in AD patients,
      and these effects of NS-398 were reversed by cyclic AMP analogue. CONCLUSION: AD
      patients manifest Th2-skewed responses to MF, CA and TR, which may be partially
      attributable to the enhanced PGE2 responses to these fungi. PV patients manifest
      Th1-skewed responses to MF.

PMID- 12190667
TI  - Increased surfactant protein D in rat airway goblet and Clara cells during
      ovalbumin-induced allergic airway inflammation.
AB  - BACKGROUND: Structural remodelling of airways in asthma that follows inflammation
      may be affected by surfactant protein D (SP-D)-mediated effects on the immune
      response. OBJECTIVE: To determine potential sites of SP-D interaction with the
      pulmonary immune response, we examined the distribution of immunoreactive SP-D in
      an experimental model of allergen-induced airway inflammation using
      immunohistochemistry, biochemical methods and in situ hybridization. METHODS: The
      experimental model used subcutaneous injection of ovalbumin in adult rats, which
      induced an airway response to inhaled nebulized ovalbumin. Three groups of rats
      (ovalbumin, ovalbumin + dexamethasone and saline) were challenged thrice weekly
      for 3 weeks. A fourth group of seven rats (naive) were taken from the same
      delivery of rats as the other groups. Lungs were then lavaged to determine total
      cell count, eosinophil count, ovalbumin-specific IgE by enzyme-linked
      immunosorbent assay and SP-D by immunoblot. Tissue samples were fixed and
      embedded, and sections were studied for the infiltration of eosinophils and for
      expression of SP-D protein by histochemistry and mRNA by in situ hybridization.
      RESULTS: Ovalbumin induced perivascular and peribronchiolar eosinophilia which
      could be prevented by dexamethasone treatment. In addition, the ovalbumin
      specific IgE levels in serum and bronchoalveolar lavage fluid of ovalbumin
      challenged animals were enhanced. Increased amount of SP-D in lavage and tissue,
      particularly in type II pneumocytes, in Clara cells and, surprisingly, in
      hyperplastic goblet cells of inflamed lungs was found. SP-D mRNA was detected in
      goblet cells as well as in type II pneumocytes and Clara cells. Dexamethasone
      treatment did not affect level of SP-D immunoreactivity. CONCLUSION: SP-D
      accumulation is increased in this model of allergen-induced eosinophilia, both in
      upper and lower airways. The increase is unaffected by dexamethasone.

PMID- 12190669
TI  - Lymph node dissection and medullary thyroid carcinoma.

PMID- 12190670
TI  - Staging of oesophageal adenocarcinoma.

PMID- 12190671
TI  - Surgical anatomy of segmental liver transplantation.
AB  - BACKGROUND: The emergence of split and living donor liver transplantation has
      necessitated re-evaluation of liver anatomy in greater depth and from a different
      perspective than before. Early attempts at split liver transplantation were met
      with significant numbers of vascular and biliary complications. Technical
      innovations in this field have evolved largely by recognizing anatomical
      anomalies and variations at operation, and devising novel ways of dealing with
      them. This has led to increasing acceptance of these procedures and decreased
      morbidity and mortality rates, similar to those observed with whole liver
      transplantation. METHODS AND RESULTS: The following review is based on clinical
      experience of more than 180 split and living related liver transplantations in
      adults and children, performed over a 7-year period from 1994 to 2001.
      CONCLUSION: A comprehensive understanding and application of surgical anatomy of
      the liver is essential to improve and maintain the excellent results of segmental
      liver transplantation.

PMID- 12190672
TI  - The mystery of liver regeneration.
AB  - BACKGROUND: Partial hepatectomy is the strongest stimulator of hepatic
      regeneration. The process of initiation and the control of the final size of the
      regenerated liver have been the subject of research for many years. A better
      understanding of this process and the effect of disease may allow better
      selection of patients for partial hepatectomy. It may also allow an insight into
      the possible application of clinical stimulation of regeneration. METHODS: Data
      were reviewed from the published literature using the Medline database. RESULTS:
      Most knowledge comes from in vitro studies and the study of resection in the rat
      model. A variety of cytokines, hormones and growth factors are involved in
      regeneration but very few have been found capable of stimulating regeneration in
      vitro. The exact interactions are not known, but there is probably a cascade
      involving different factors at differing stages of regeneration. CONCLUSION:
      Further in vivo research should allow greater understanding of liver
      regeneration, thereby providing a potential therapeutic tool in patients for whom
      regeneration has failed, or is likely to fail. Such research is also important in
      respect of liver support devices, which may inhibit liver regeneration by
      filtration of many of the factors involved.

PMID- 12190673
TI  - Systematic review of the efficacy and safety of colorectal stents.
AB  - BACKGROUND: Colorectal stents are being used for palliation and as a 'bridge to
      surgery' in obstructing colorectal cancers. METHODS: A systematic review of the
      published data on stenting for the treatment of colorectal obstruction was
      carried out by searching Medline and other online databases for the period from
      January 1990 to December 2000. A total of 58 publications (case series, single
      case reports and reviews) was found, of which 29 case series were included in the
      analysis. Technical and clinical success, complications and reobstruction, both
      in palliation and as a 'bridge to surgery', were assessed. Both descriptive
      statistics and pooled analyses were carried out. RESULTS: Pooled results showed
      that stent insertion was attempted in 598 instances. Technical success was
      achieved in 551 (92 per cent) and clinical success in 525 (88 per cent).
      Palliation was achieved in 302 (90 per cent) of 336 cases, while 223 (85 per
      cent) of 262 insertions succeeded as a 'bridge to surgery' (95 per cent had a one
      stage surgical procedure). There were three deaths (1 per cent). Perforation
      occurred 22 times (4 per cent). Stent migration was reported in 54 (10 per cent)
      of 551 technically successful cases. The rate of stent reobstruction was 52 (10
      per cent) of 525, mainly in the palliative group. CONCLUSION: Evidence suggests
      that colorectal stents offer good palliation, and are safe and effective as a
      'bridge to surgery'. Stent usage can avoid the need for a stoma, and is
      associated with low rates of mortality and morbidity. Dilatation of malignant
      strictures at the time of stent placement appears to be dangerous and should be
      avoided.

PMID- 12190674
TI  - Randomized clinical trial of specific lactobacillus and fibre supplement to early
      enteral nutrition in patients with acute pancreatitis.
AB  - BACKGROUND: Microbial infection of the pancreatic tissue in patients with severe
      acute pancreatitis increases the morbidity and mortality rates. Colonization of
      the lower gastrointestinal tract and oropharynx with Gram-negative, but sometimes
      also Gram-positive, bacteria precedes contamination of the pancreas. The aim of
      this study was to determine whether lactic acid bacteria such as Lactobacillus
      plantarum 299 could prevent colonization of the gut by potential pathogens and
      thus reduce the endotoxaemia associated with acute pancreatitis. METHODS:
      Patients with acute pancreatitis were randomized into two double-blind groups.
      The treatment group received a freeze-dried preparation containing live L.
      plantarum 299 in a dose of 109 organisms, together with a substrate of oat fibre,
      for 1 week by nasojejunal tube. The control group received a similar preparation
      but the Lactobacillus was inactivated by heat. RESULTS: A total of 45 patients
      completed the study. Twenty-two patients received treatment with live and 23 with
      heat-killed L. plantarum 299. Infected pancreatic necrosis and abscesses occurred
      in one of 22 patients in the treatment group, compared with seven of 23 in the
      control group (P = 0.023). The mean length of stay was 13.7 days in the treatment
      group versus 21.4 days in the control group (P not significant). CONCLUSION:
      Supplementary L. plantarum 299 was effective in reducing pancreatic sepsis and
      the number of surgical interventions.

PMID- 12190675
TI  - Randomized clinical trial comparing quality of life after straight and pouch
      coloanal reconstruction.
AB  - BACKGROUND: Functional results after rectal resection with straight coloanal
      anastomosis are poor. While most functional aspects are improved with coloanal J
      pouch anastomosis, it is still unclear whether this translates into better
      quality of life. The aim of this trial was to investigate health-related quality
      of life as a primary endpoint in patients undergoing sphincter-saving rectal
      resection. METHODS: Sixty-four patients were randomized to either straight (n =
      32) or coloanal J pouch (n = 32) anastomosis. Patients were studied before
      operation, at the time of stoma reversal and at 3-month intervals for 1 year
      thereafter. Quality of life was measured using two generic (Gastrointestinal
      Quality of Life Index and European Organization for Research and Treatment of
      Cancer (EORTC) QLQ-C30) and one disease-specific (EORTC QLQ-CR38) instruments.
      Functional results using a standardized score as well as manometric variables
      were recorded. RESULTS: Thirty-nine patients (19 with a pouch and 20 with a
      straight anastomosis) completed the trial. There was a marked difference between
      the two groups with regard to quality of life profile. Patients with a pouch
      reconstruction had a significantly better quality of life, particularly in the
      early postoperative period. CONCLUSION: Patients undergoing low anterior rectal
      resection and coloanal J pouch reconstruction may expect not only better
      functional results but also an improved quality of life in the early months after
      surgery compared with patients who receive a straight coloanal anastomosis.

PMID- 12190676
TI  - Long-term outcome of hepaticojejunostomy with routine access loop formation
      following iatrogenic bile duct injury.
AB  - BACKGROUND: Hepaticojejunostomy is the 'gold standard' procedure for repairing
      iatrogenic bile duct injuries. The aim of this study was to examine the long-term
      outcome following hepaticojejunostomy for iatrogenic bile duct injury and the
      utility of routine construction of an access loop. METHODS: Patients with
      iatrogenic biliary injuries were treated with hepaticojejunostomy and access loop
      by a single surgeon. Injuries were classified according to the Bismuth level. An
      'excellent' outcome was achieved if the patient never experienced jaundice or
      cholangitis in the follow-up period, and the outcome was 'good' if the patient
      developed symptoms but was asymptomatic for more than 12 months. RESULTS: Forty
      eight patients underwent such operation. There was one operative death. Thirty
      three patients were followed for 3 years or more (mean follow-up 80.4 (range 46
      118) months). Thirteen of the 33 injuries were Bismuth level II, 13 were Bismuth
      level III and seven were Bismuth level IV. Outcome was dependent on the Bismuth
      level (P < 0.001). It was excellent in all 13 patients with Bismuth level II
      injuries, excellent in seven and good in six of the 13 patients with Bismuth
      level III injuries, and excellent in one and good in six of the seven patients
      with Bismuth level IV injuries. Moreover, the need for access loop intervention
      was dependent on the Bismuth level (P < 0.001). No patient with Bismuth level II
      injury required intervention, compared with five of 13 with Bismuth level III and
      six of seven with Bismuth level IV injuries. CONCLUSION: Biliary reconstruction
      affords satisfactory long-term outcome. The likelihood of needing the access loop
      for radiological intervention is dependent on the Bismuth level. The authors
      recommend that an access loop be constructed in all patients with Bismuth level
      III and IV injuries.

PMID- 12190677
TI  - Spontaneous tumour rupture and prognosis in patients with hepatocellular
      carcinoma.
AB  - BACKGROUND: Hepatocellular carcinoma (HCC) is a common disease in Taiwan.
      Ruptured HCC is an uncommon and potentially fatal complication of the condition.
      Information on the impact of ruptured HCC on hepatic resection is, however,
      limited. METHODS: The clinical features of 60 patients with ruptured HCC who
      underwent hepatic resection from 1986 to 1998 were reviewed. Clinical features
      and factors influencing the outcome of 475 patients with non-ruptured HCC were
      used for comparison. RESULTS: Of 535 surgically resected HCCs, 60 (11.2 per cent)
      were ruptured. Univariate analysis showed that sudden onset of abdominal pain,
      physical signs of haemodynamic unstability, reduced haemoglobin level and a
      raised aspartate aminotransferase level were more frequently found in patients
      with ruptured HCC than in those with non-ruptured tumours. Multivariate stepwise
      logistic regression analysis revealed sudden-onset abdominal pain to be the only
      independently significant factor in patients in the ruptured HCC group. The 1-, 3
      and 5-year survival rates of patients with non-ruptured HCC were 72.1, 47.3 and
      33.9 per cent, and those of patients with ruptured HCC were 54.2, 35.0 and 21.2
      per cent respectively. Similar overall survival rates were found in patients with
      ruptured and non-ruptured HCC, although patients in the non-ruptured HCC group
      had a significantly better disease-free survival rate (P = 0.023). CONCLUSION:
      The presence of sudden-onset abdominal pain is the only independent indicator of
      ruptured HCC. Hepatic resection, when feasible, is the treatment of choice and
      can result in an overall survival rate comparable to that of patients with non
      ruptured HCC.

PMID- 12190678
TI  - Perineural invasion has a negative impact on survival of patients with
      gallbladder carcinoma.
AB  - BACKGROUND: The clinical significance of perineural invasion of gallbladder
      carcinoma remains unclear. The aim of this study was to elucidate the incidence
      and mode of perineural invasion of gallbladder carcinoma and clarify its
      prognostic significance. METHODS: A clinicopathological study was conducted on 68
      patients who underwent attempted curative resection for gallbladder carcinoma.
      According to the pathological tumour node metastasis (pTNM) classification of the
      Union Internacional Contra la Cancrum, there were five (7 per cent), nine (13 per
      cent), 20 (29 per cent) and 34 (50 per cent) patients with pT1, pT2, pT3 and pT4
      disease respectively. Twenty patients (29 per cent) had pM1 disease, including
      involved para-aortic nodes, liver metastases and localized dissemination.
      RESULTS: The overall incidence of perineural invasion was 71 per cent (48 of 68
      patients). Forty-four (96 per cent) of 46 patients with extrahepatic bile duct
      invasion had perineural invasion. Although several histological factors were
      associated with perineural invasion, multivariate analysis demonstrated that
      extrahepatic bile duct invasion was the only significant factor correlated with
      perineural invasion (odds ratio 99.0, P < 0.001). The perineural invasion index,
      defined as the ratio of the number of involved nerves to the total number of
      nerves examined, was significantly higher at the centre than in the proximal and
      distal parts of the tumour in the 46 patients with extrahepatic bile duct
      invasion (P < 0.001). The 5-year survival rate for patients with perineural
      invasion was significantly lower than that for patients with no invasion (7
      versus 72 per cent; P < 0.001). Cox proportional hazard analysis identified
      perineural invasion (relative risk (RR) 5.3, P < 0.001) and lymph node metastasis
      (RR 2.5, P = 0.008) as significant independent prognostic factors. CONCLUSION:
      Perineural invasion is common in advanced gallbladder carcinoma and has a
      significant negative impact on patient survival.

PMID- 12190679
TI  - Acute colonic diverticulitis in patients under 50 years of age.
AB  - BACKGROUND: There is ongoing controversy concerning the virulence and management
      of diverticulitis in young patients. This study reports on the management of
      acute diverticulitis with reference to the virulence and outcome of the disease
      with respect to age. METHODS: Between January 1994 and June 1999, 327 patients
      were treated for acute left colonic diverticulitis. Patients were divided in two
      groups: those aged 50 years or less (group 1, 72 patients) and those older than
      50 years (group 2, 255 patients). The diagnosis was confirmed histologically or
      radiologically in all patients. RESULTS: There were differences in gender
      distribution related to age (P < 0.001). During the first hospital stay, 226
      patients (69.1 per cent) had successful conservative treatment, 78 (23.9 per
      cent) needed emergency surgery and 23 (7.0 per cent) had a semielective operation
      (P = 0.47). The recurrence rate was 25.5 per cent in group 1 and 22.3 per cent in
      group 2 (P = 0.93). The type of surgical procedure and grade of peritonitis in
      emergency patients were similar in the two groups. Overall the mortality rate in
      patients who underwent an operation was 16.3 per cent. The mortality rate was
      zero in group 1 and 2.2 per cent in group 2 after elective or semielective
      operation (P = 1.0), and zero in group 1 and 34.9 per cent in group 2 after
      emergency operation (P < 0.001). CONCLUSION: Diverticulitis in young patients
      does not have a particularly aggressive course and the risk of recurrence is
      similar to that of older patients.

PMID- 12190680
TI  - Impact of the introduction and training of total mesorectal excision on
      recurrence and survival in rectal cancer in The Netherlands.
AB  - BACKGROUND: Local control and survival following surgical treatment of rectal
      cancer have been improved by the introduction of total mesorectal excision (TME).
      The aim of this study was to determine the nationwide impact of the introduction
      and training of TME on recurrence and survival in rectal cancer. METHODS: Short-
      and long-term outcomes of a recently published trial of rectal cancer surgery
      (TME trial) were compared with results from an older trial (cancer recurrence and
      blood transfusion (CRAB) trial), in which conventional surgery was performed
      without quality control. Only patients who were operated on with curative intent
      and who did not receive neoadjuvant radiotherapy were studied. Differences in
      clinicopathological characteristics were corrected for by multivariate analysis.
      To ensure valid comparisons, only events that occurred within 2 years of
      operation were analysed with regard to long-term outcome. RESULTS: In the
      univariate analysis, a higher clinical anastomotic leak rate was found in
      patients following low anterior resection in the TME trial (P = 0.046), but this
      association was not significant in the multivariate analysis. The local
      recurrence rate decreased from 16 per cent in the CRAB trial to 9 per cent in the
      TME trial, and type of operation (conventional (CRAB trial) versus TME (TME
      trial)) was an independent predictor of local recurrence (P = 0.002). Type of
      operation was also an independent predictor of overall survival (P = 0.019);
      there was a higher survival rate in the TME trial. CONCLUSION: The introduction
      and training of TME has led to improved long-term outcome of patients with rectal
      cancer in the Netherlands.

PMID- 12190681
TI  - Evaluation of POSSUM in patients with oesophageal cancer undergoing resection.
AB  - BACKGROUND: The Physiogical and Operative Severity Score for the enUmeration of
      Mortality and morbidity (POSSUM) has been used to produce a numerical estimate of
      expected mortality and morbidity after a variety of general surgical procedures.
      The aim of this study was to evaluate the ability of POSSUM to predict mortality
      and morbidity in patients undergoing oesophagectomy. METHODS: POSSUM predictor
      equations for morbidity and mortality were applied retrospectively to 204
      patients who had undergone oesophagectomy for cancer. Observed morbidity and
      mortality rates were compared with rates predicted by POSSUM using the Hosmer
      Lemeshow goodness-of-fit test. Evaluation of the discriminative capability of
      POSSUM predictor equations was performed using receiver-operator characteristic
      (ROC) curve analysis. RESULTS: The observed and predicted mortality rates were
      12.7 and 19.1 per cent respectively, and the respective morbidity rates were 53.4
      and 62.3 per cent. However, the POSSUM model showed a poor fit with the data both
      for the observed 30-day mortality (chi2 = 16.26, P = 0.002) and morbidity (chi2 =
      63.14, P < 0.001) using the Hosmer-Lemeshow test. ROC curve analysis revealed
      that POSSUM had poor predictive accuracy both for mortality (area under curve
      0.62) and morbidity (area under curve 0.55). CONCLUSION: These data suggest that
      POSSUM does not accurately predict mortality and morbidity in patients undergoing
      oesophagectomy and must be modified.

PMID- 12190682
TI  - Surgical management of and long-term survival after adenocarcinoma of the cardia.
AB  - BACKGROUND: The choice of surgical strategy for patients with adenocarcinoma of
      the oesophagogastric junction is controversial. This study was performed to
      analyse the surgical results of a 20-year experience with these lesions. METHODS:
      From January 1981 to January 2001, 126 patients with adenocarcinoma of the cardia
      underwent resection in the authors' institution. The treatment of choice was
      oesophagectomy for type I tumours, and extended gastrectomy for type II and III
      lesions. Morbidity, mortality and survival were determined retrospectively.
      RESULTS: Fifty-six patients (44.4 per cent) had type I tumours, 44 (34.9 per
      cent) type II and 26 (20.6 per cent) type III. Primary resection was performed in
      113 patients (89.7 per cent). Oesophagectomy with resection of the proximal
      stomach was carried out in 65 patients (51.6 per cent) and extended total
      gastrectomy with transhiatal resection of the distal oesophagus in 61 (48.4 per
      cent). In-hospital mortality and morbidity rates were 4.8 and 34.1 per cent
      respectively. The overall 3- and 5-year survival rates were 40.9 and 25.1 per
      cent respectively, and were not affected by the surgical approach. Survival was
      significantly associated with R0 resection, pathological node-positive category,
      postoperative complications and tumour differentiation. CONCLUSION: Postoperative
      mortality, morbidity and long-term survival did not appear to be affected by
      surgical approach. Further prospective studies are needed to confirm the
      equivalence between transthoracic and transabdominal approaches.

PMID- 12190683
TI  - Sequential resection of lung metastasis following partial hepatectomy for
      colorectal cancer.
AB  - BACKGROUND: Multiple organ metastases from colorectal carcinoma may be considered
      incurable, but long survival after both liver and lung resection for metastases
      has been reported. METHODS: A retrospective analysis of 48 patients who underwent
      lung resection for metastatic colorectal cancer between 1992 and 1999 was
      undertaken. Twenty-seven patients had lung metastasis alone, 15 had previous
      partial hepatectomy, and six had previous resection of local or lymph node
      recurrence. The relationship of clinical variables to survival was assessed.
      Survival was calculated from the time of first pulmonary resection. RESULTS: Five
      year survival rates after resection of lung metastasis were 73 per cent in
      patients without preceding recurrence, 50 per cent following previous partial
      hepatectomy and zero after resection of previous local recurrence. Independent
      prognostic variables that significantly affected survival after thoracotomy were
      primary tumour histology and type of preceding recurrence. There was no
      significant difference in survival after lung resection between patients who had
      sequential liver and lung resection versus those who had lung resection alone.
      CONCLUSION: Sequential lung resection after partial hepatectomy for metastatic
      colorectal cancer may lead to long-term survival.

PMID- 12190684
TI  - Clinical experience in continuous graft monitoring with microdialysis early after
      liver transplantation.
AB  - BACKGROUND: Early detection of impaired graft function after transplantation is
      essential. Microdialysis permits continuous monitoring of metabolic changes by
      mimicking the passive function of a capillary blood vessel by perfusion of a
      tubular semipermeable membrane introduced into the tissue. Based on the results
      of animal experiments, a clinical pilot study was undertaken. METHODS: Ten
      consecutive patients undergoing whole-organ orthotopic liver transplantation were
      studied. Intrahepatic implantation of a microdialysis catheter was performed at
      the end of the operation. A reference catheter was placed in the subcutaneous
      tissue over the right pectoral area immediately after abdominal closure.
      Consecutive serial samples were collected at 1-h intervals for 3 days after the
      operation. Glucose, lactate, pyruvate and glycerol concentrations were measured.
      RESULTS: During the first 24 h, the glucose level was higher in the liver than in
      reference tissue. Initially, increased mean(s.e.m.) levels of lactate (7.0(1.9)
      mmol/l) were observed in the liver, with a rapid decrease (to 2.7(0.3) mmol/l)
      over 24 h. A decrease in, and later stabilization of, the lactate : pyruvate
      ratio in the liver, from 18.7(4.2) to 10.0(1.1), was observed within 24 h after
      transplantation. Liver glycerol levels decreased from 62.3(7.4) to 24.3(7.5)
      micro mol/l within the first 16 h after reperfusion and remained stable
      thereafter. CONCLUSION: Microdialysis allows continuous monitoring of tissue
      metabolism in the transplanted liver. The procedure is easy to perform and safe.
      The specific detection and monitoring of pathological changes in the liver graft
      (e.g. arterial and portal vein thrombosis, or early rejection) with microdialysis
      should be addressed in further studies.

PMID- 12190685
TI  - Identifying patients for blood conservation strategies.
AB  - BACKGROUND: Generally, only the type of operation is used to estimate the need
      for perioperative homologous blood transfusion. This study quantified the extent
      to which the estimation could be improved if, in addition, simple patient
      characteristics were taken into account. METHODS: Retrospective data on 24 509
      consecutive adult surgical patients were used to derive and validate three models
      to predict perioperative homologous transfusion. The first model was a
      univariable model with type of operation as the only predictor. The second and
      third models were a full and a simplified multivariable logistic regression
      model. The performance of the multivariable models was tested in two validation
      sets: in similar patients who had operations in the same general hospital
      (internal validation) and in patients who had operations in a university hospital
      (external validation). The areas under the receiver-operator characteristic (ROC)
      curve were compared with that found in the derivation set. RESULTS: There were no
      important differences in characteristics between the derivation and validation
      sets. The ROC area of the model including surgery only was 0.92 (99 per cent
      confidence interval (c.i.) 0.91 to 0.94) and that of the full and simplified
      multivariable models 0.95 (99 per cent c.i. 0.94 to 0.96) and 0.94 (99 per cent
      c.i. 0.93 to 0.95) respectively. The latter two were significantly different from
      the first one. In the external validation set the ROC area of the simplified
      model was 0.84 (95 per cent c.i. 0.83 to 0.86). Patients who had a preoperative
      haemoglobin level lower than 13 g/dl and underwent major invasive surgery had the
      highest risk (43 per cent) of transfusion. CONCLUSION: A simple algorithm using
      type of operation and haemoglobin concentration was effective in identifying
      patients likely to need perioperative homologous blood transfusion.

PMID- 12190686
TI  - Assessment of the physical properties of endoscopic retrieval systems.
AB  - BACKGROUND: A reliable method of retrieval of laparoscopically resected organs is
      required. The physical properties of three commercial systems available for
      clinical use (two plastic, one woven fabric) were examined. METHODS: Pig
      abdominal walls and gallbladders containing steel balls to represent gallstones
      were used to simulate organ retrieval on 60 occasions. The performance of
      retrieval bags was measured in terms of the temporal profile of pressure
      developed inside the bag, the force on the bag during withdrawal, and whether or
      not the bag could be retrieved intact. The force versus elongation relationship
      was also determined for each bag. RESULTS: Although there was a wide range of
      maximum pressures recorded (14-320 mmHg) with each retrieval system, the mean
      pressures in the plastic systems were significantly higher. The forces recorded
      during attempted withdrawal of both plastic bags were significantly lower than
      those with the fabric system (BERT bag: mean (range) 87 (25-165) N; Endocatch: 40
      (7-123) N; Endopouch: 40 (14-68) N; P = 0.005 Endocatch versus BERT, P = 0.004
      Endopouch versus BERT). The BERT bags tore more easily at the site of the
      grasper. CONCLUSION: Plastic retrieval systems were less likely to burst than
      fabric systems when subjected to simulated retrieval, and required less force for
      withdrawal. Plastic systems may therefore be associated with less tumour seeding
      or gallstone spillage as a consequence of bag disruption.

PMID- 12190687
TI  - Experience in the management of conjoined twins.
AB  - BACKGROUND: Conjoined twins occur in approximately one in 200 000 live births.
      Their management is often extremely complex and experience with large numbers is
      restricted to a few centres worldwide. METHODS: An analysis of 17 sets of
      symmetrical conjoined twins managed by a single team of surgeons over a 16-year
      period was undertaken. RESULTS: Management could be divided into three groups.
      Those in group 1 (n = 5) had non-operative management, owing to cardiac fusion or
      gross anatomical union, and all died. Those in group 2 (n = 7) underwent
      emergency separation, when one twin was dead or threatening the survival of the
      sibling or where there was a correctable life-threatening associated anomaly
      (four of 14 survived). Twins in group 3 (n = 5) underwent elective separation,
      allowing time for detailed preoperative investigation and planning (eight of ten
      survived). CONCLUSION: Accurate preoperative investigation, a team approach,
      previous experience, and meticulous operative and postoperative management
      contributed to the success rate achieved in this series.

PMID- 12190688
TI  - Randomized clinical trial assessing the side-effects of glyceryl trinitrate and
      diltiazem hydrochloride in the treatment of chronic anal fissure (Br J Surg 2002;
      89: 413-17).

PMID- 12190689
TI  - Randomized clinical trial assessing the side-effects of glyceryl trinitrate and
      diltiazem hydrochloride in the treatment of chronic anal fissure (Br J Surg 2002;
      89: 413-17).

PMID- 12190692
TI  - Impact of socioeconomic deprivation on outcome after surgery for colorectal
      cancer (Br J Surg 2002; 89: 586-90).

PMID- 12190691
TI  - Levels of the chemokines growth-related oncogene alpha and epithelial neutrophil
      activating protein 78 are raised in patients with severe acute pancreatitis (Br J
      Surg 2002; 89: 566-72).

PMID- 12190693
TI  - Ultrasonography is superior to plain radiography in the diagnosis of
      pneumoperitoneum (Br J Surg 2002; 89: 351-4).

PMID- 12190710
TI  - Childhood mania, attention deficit hyperactivity disorder and conduct disorder: a
      critical review of diagnostic dilemmas.
AB  - OBJECTIVES: Significant debate exists on whether early onset bipolar disorder is
      mistakenly attributed to attention deficit hyperactivity disorder (ADHD) or
      conduct disorder (CD), or whether ADHD and CD are frequently misdiagnosed as
      mania. We review the literature on the extent to which these disorders can be
      reliably differentiated, and describe the diagnostic confusion that may be the
      result of features common to both classes of disorders. METHODS: The review
      focuses on research studies that have examined whether overlapping symptoms of
      bipolar disorder, ADHD, and CD contribute to misdiagnosis of the two classes of
      disorders, the prevalence of early onset bipolar disorder with comorbid ADHD or
      CD, and theories regarding the origins of this comorbidity. RESULTS: Reliable and
      accurate diagnoses can be made despite the symptom overlap of bipolar disorder
      with ADHD and CD. Children with bipolar disorder and ADHD may have a distinct
      familial subtype of bipolar disorder. Some findings suggest that manic symptoms
      may represent 'noise' that indicates the general severity of psychopathology in a
      child or adolescent. CONCLUSIONS: Further prospective studies may confirm whether
      early onset bipolarity can be successfully differentiated from ADHD or CD,
      whether all three types of disorders can be recognized in comorbid cases, or
      whether comorbid cases represent a distinct subtype of bipolar disorder.

PMID- 12190712
TI  - Impact of axis II comorbidity on the course of bipolar illness in men: a
      retrospective chart review.
AB  - OBJECTIVES: The purpose of this study was to investigate whether the presence of
      comorbid personality disorder influences the course of bipolar illness. METHODS:
      Fifty-two euthymic male bipolar I out-patients were assessed using the Structured
      Clinical Interview for DSM-III-R Personality Disorders (SCID II). Bipolar
      patients with an axis II diagnosis were compared with those without an axis II
      diagnosis on retrospectively obtained demographic, clinical and course of illness
      variables. RESULTS: Thirty-eight percent of the bipolar patients met criteria for
      an axis II diagnosis. Two (4%) met criteria for (only) a Cluster A disorder, four
      (8%) for (only) a Cluster B, and six (12%) for (only) a Cluster C disorder. One
      (2%) bipolar patient met criteria a disorder in both Clusters A and B, and one
      (2%) for a disorder in Clusters B and C. Five (10%) met criteria for at least one
      disorder in Clusters A and C, and one met criteria for disorders in Clusters A,
      B, and C. The presence of a personality disorder was significantly associated
      with a lower rate of current employment, a higher number of currently prescribed
      psychiatric medications, and a higher incidence of a history of both alcohol and
      substance use disorders compared with the bipolar patients without axis II
      pathology. CONCLUSIONS: Our results extend previous findings of an association
      between comorbid personality disorder in bipolar I patients and factors that
      suggest a more difficult course of bipolar illness.

PMID- 12190711
TI  - Design and implementation of a randomized trial evaluating systematic care for
      bipolar disorder.
AB  - OBJECTIVES: Everyday care of bipolar disorder typically falls short of evidence
      based practice. This report describes the design and implementation of a
      randomized trial evaluating a systematic program to improve quality and
      continuity of care for bipolar disorder. METHODS: Computerized records of a large
      health plan were used to identify all patients treated for bipolar disorder.
      Following a baseline diagnostic assessment, eligible and consenting patients were
      randomly assigned to either continued usual care or a multifaceted intervention
      program including: development of a collaborative treatment plan, monthly
      telephone monitoring by a dedicated nurse care manager, feedback of monitoring
      results and algorithm-based medication recommendations to treating mental health
      providers, as-needed outreach and care coordination, and a structured
      psychoeducational group program (the Life Goals Program by Bauer and McBride)
      delivered by the nurse care manager. Blinded assessments of clinical outcomes,
      functional outcomes, and treatment process were conducted every 3 months for 24
      months. RESULTS: A total of 441 patients (64% of those eligible) consented to
      participate and 43% of enrolled patients met criteria for current major
      depressive episode, manic episode, or hypomanic episode. An additional 39%
      reported significant subthreshold symptoms, and 18% reported minimal or no
      current mood symptoms. Of patients assigned to the intervention program, 94%
      participated in telephone monitoring and 70% attended at least one group session.
      CONCLUSIONS: In a population-based sample of patients treated for bipolar
      disorder, approximately two-thirds agreed to participate in a randomized trial
      comparing alternative treatment strategies. Nearly all patients accepted regular
      telephone monitoring and over two-thirds joined a structured group program.
      Future reports will describe clinical effectiveness and cost-effectiveness of the
      intervention program compared with usual care.

PMID- 12190713
TI  - Are patients with bipolar affective disorder socially disadvantaged? A comparison
      with a control group.
AB  - BACKGROUND: Bipolar affective disorder (BPAD) has considerable implications for
      personal and social functioning. However a tendency to be over-represented in
      high socio-economic classes has been reported in earlier studies, suggesting that
      social disadvantage accompanying the illness is not severe. In addition, an
      association between affective disorders in general and increased residential
      mobility has been suggested, but it is unclear if such an association exists with
      BPAD. OBJECTIVES: (1) To investigate the suggestion made in previous studies that
      patients with bipolar disorder are advantaged socially. (2) To test the
      hypothesis that patients with bipolar disorder show greater residential mobility
      compared with other patients with psychiatric disorders. METHODS: Ninety patients
      with DSM IV diagnosis of bipolar disorder admitted to the acute in-patient unit
      of a public-financed district psychiatric service in Dublin were compared with a
      control group of 91 randomly selected patients with other psychiatric diagnoses,
      excluding schizophrenia. Socio-economic, educational and employment ratings were
      compared, and also duration of illness, frequency of admission and residential
      mobility. The data were collected retrospectively from case notes and through
      semistructured interviews with patients or their relatives. The bipolar group was
      compared with the control group and to the unipolar depression subgroup. RESULTS:
      The bipolar and control groups were found to have similar demographic and socio
      economic features, although the bipolar group had more years of education
      compared with the whole control group but not when compared with the unipolar
      depression group. The bipolar group showed longer duration of psychiatric
      disorder, more frequent hospital admissions and more frequent residential moves
      since the onset of the illness. CONCLUSION: Bipolar patients requiring in-patient
      care in this service experience severe disruption to their lives over prolonged
      periods.

PMID- 12190715
TI  - Multifamily psychoeducation groups (MFPG) for families of children with bipolar
      disorder.
AB  - OBJECTIVES: Multi-family psychoeducation groups (MFPG) have been developed and
      tested for adults, but not for children with bipolar disorder (BPD). We present
      data from a pilot study of our manual-driven MFPG treatment for families of
      children with mood disorders and address two questions: Do families of children
      with BPD and families of children with major depressive disorder/dysthymic
      disorder (MDD/DD): 1) differ at treatment entry?; 2) benefit equally from
      intervention? METHOD: A total of 35 children (n=16, BPD; n=19, MDD/DD) aged 8-11
      years and their parents were randomized into immediate MFPG plus treatment as
      usual (TAU) or wait-list + TAU and assessed periodically. RESULTS: At baseline,
      there was a trend toward parents in BPD families being more knowledgeable about
      mood symptoms than parents in MDD/DD families (p < 0.04). Additionally at
      baseline, children with BPD evidenced greater mood severity historically and a
      trend toward more hospitalizations, day treatment, outpatient treatment,
      medication trials, and placement in special education classrooms than children
      with MDD/DD. Immediately following and 4 months post-treatment, both BPD and
      MDD/DD families described having gained knowledge, skills, support, and positive
      attitudes during treatment. MDD/DD families increased their knowledge of symptoms
      to the same level as BPD families. CONCLUSIONS: While BPD families enter
      treatment with more impaired children and more extensive treatment histories,
      both BPD and MDD/DD families benefit from intervention. The clinical issues
      concerning combining families of children with bipolar and depressive spectrum
      illnesses in groups are discussed. Clinical impressions suggest that such
      combinations are clinically feasible and potentially beneficial.

PMID- 12190714
TI  - A measure for assessing patient perception of provider support for self
      management of bipolar disorder.
AB  - OBJECTIVES: Health care providers have an important role in acknowledging and
      supporting patients' self-management of chronic illnesses such as bipolar
      disorder. This report describes the development and evaluation of a brief measure
      for assessing patient perception of providers' support for self-management of
      bipolar disorder. METHODS: A 10-item measure was developed combining generic
      items from an existing measure of providers' autonomy supportive versus
      controlling style with items specific to the self-management of bipolar disorder.
      The psychometric properties of the measure and its relation to clinical variables
      were evaluated in a sample of patients enrolled in an ongoing randomized
      intervention trial. RESULTS: Data were obtained from 420 patients with a chart
      diagnosis of bipolar disorder (mean age=44, 68% female, 88% Caucasian). The
      proportion of missing responses for items ranged from 0 to 3%. Reliability
      coefficient alpha for the full scale was 0.94. Corrected item-total correlations
      for individual items ranged from 0.70 to 0.83. Factor analysis identified a
      single factor accounting for 67% of total variance. Factor loadings for
      individual items were all at least 0.75. The measure showed moderate positive
      correlations with measures of self-efficacy for managing bipolar disorder
      (r=0.34; p < 0.001), treatment satisfaction (r=0.63; p < 0.001), small negative
      correlations with measures of mania symptoms (r=-0.11; p < 0.03) and depressive
      symptoms (r=-0.09; p < 0.10). CONCLUSIONS: This measure shows good psychometric
      properties and good evidence for convergent and discriminant validity. It is
      promising for assessing an important aspect of care for bipolar disorder.

PMID- 12190716
TI  - The influence of successful prophylactic drug treatment on cognitive dysfunction
      in bipolar disorders.
AB  - BACKGROUND: Cognitive variables such as negative self-evaluations have been
      discussed as vulnerability factors for depressive syndromes. In the context of
      bipolar disorders dysfunctional cognitive structures have received little
      interest as these patients seem to be less disturbed during the euthymic interval
      than patients with major depression. METHODS: In the present study, the self
      esteem of remitted patients with DSM-III-R diagnosis of major depression (n=20),
      bipolar disorder (n=20) and healthy controls (n=20) was measured with the
      Frankfurt Self-concept Scale (FSKN). RESULTS: 1) Statistical analysis by analysis
      of variance (ANOVA) showed no significant differences as to age, sex, etc.
      between the psychiatric groups. The clinical groups showed lower self-esteem
      ratings in comparison to healthy controls. 2) Four groups (T1-T4) of remitted
      patients with bipolar disorders (20 in each group) were successfully maintained
      on mood stabilizers (lithium or carbamazepine) and classified by the duration of
      their episode-free period. T1 included those who were episode-free for only the
      week before discharge from hospital. T2 were symptom-free for <30 months. T3 were
      episode-free for >30 months and <60 months. T4 were episode-free for >60 months.
      The comparison of their FSKN self-esteem ratings by ANOVA suggests that self
      esteem improves during successful prophylactic treatment. A posteriori contrasts
      indicate a normalized self-esteem after a bipolar episode-free period of at least
      47 months. CONCLUSIONS: Dysfunctional cognitions can be demonstrated in unipolar
      as well as in bipolar patients. Successful episode-preventive medication with
      mood stabilizers seems to counteract lowered self-esteem. Adjunctive cognitive
      therapy might help to optimize the long-term course of bipolar disorder.

PMID- 12190717
TI  - Topiramate in treatment-resistant depression and binge-eating disorder.

PMID- 12190718
TI  - Estimation of lithium dose requirement by body weight.

PMID- 12190719
TI  - Cognitive behaviour therapy in the treatment of bipolar disorder.

PMID- 12190720
TI  - Issues of consent and privacy affecting the functioning of ASERNIP-S.

PMID- 12190721
TI  - Factors affecting surgical outcome in the elderly at Auckland Hospital.
AB  - BACKGROUND: The aim of the present study was to define the factors which affect
      the outcome of major abdominal surgery in elderly patients. METHOD: Data were
      collected prospectively using the surgical audit on all patients who were 65
      years-old or older and had undergone major abdominal surgery at Auckland Hospital
      between January 1997 and November 2000. Risk factors studied were age, sex,
      American Society of Anesthesiologists grade, operative duration, timing of
      surgery (elective, urgent or emergency), surgeon (consultant or registrar) and
      the presence of the scrubbed consultant in theatre. Surgical outcome (no
      complications, complications or death) was defined according to the complication
      stratification and severity score developed by the University of Otago. Direct
      logistic regression was used to determine the significance of the risk factors.
      RESULTS: 1141 patients (614 women and 527 men) who underwent 1248 procedures were
      studied. The factors that affected the mortality were the ASA grade (P = 0.0001)
      and operative timing (P = 0.0008). The factors that affected the severity of
      postoperative complications were ASA (P = 0.0001), operative timing (P = 0.0001)
      and duration (P = 0.0001). CONCLUSIONS: The ASA, timing and duration of surgery
      were the most significant factors affecting patient outcome. Age had a less
      important effect. Arranged surgery and short operative duration have a favourable
      outcome in selected elderly patients. Therefore, the elderly should not be denied
      indicated major abdominal surgery on basis of age alone.

PMID- 12190723
TI  - Same-day lymphoscintigraphy and sentinel node biopsy for early breast cancer.
AB  - BACKGROUND: Lymphoscintigraphy and sentinel node biopsy are currently being
      assessed as an alternative to axillary dissection for staging in early breast
      cancer. However, little is known about the optimum timing of surgery following
      injection of the radio-isotope into the breast. The aim of the present study was
      to establish whether lymphoscintigraphy on the morning of surgery allowed
      efficacious and accurate sentinel node identification and biopsy. METHODS: We
      reviewed our experience of 216 consecutive cases of lymphoscintigraphy in early
      breast cancer using peritumoural injections of technetium99m antimony sulphide
      colloid and subsequent sentinel node biopsy using a hand-held gamma probe and
      blue dye. The time interval between radioisotope injection and successful
      intraoperative identification of the sentinel node was assessed and whether this
      was associated with certain clinical and histological variables. RESULTS: The
      sentinel node was identified by lymphoscintigraphy in 160 cases (74%) at a median
      time duration of 40 min post injection. The median time duration between isotope
      injection and surgery was 5 h. Of the 160 cases where the sentinel node was
      visualized at lymphoscintigraphy, sentinel node biopsy was successfully performed
      in 155 cases (97%). This compares with 25/56 (45%) cases where lymphoscintigraphy
      failed to localize the sentinel node (P < 0.0001). There was no association found
      between the injection of the radioisotope greater or less than 5 h before surgery
      and the successful intraoperative identification of the sentinel node. Failure to
      identify the sentinel node at lymphoscintigraphy beyond 3 h was associated with a
      low intraoperative identification rate. There was no correlation found between
      intraoperative identification of the sentinel node according to the duration of
      isotope injection in relation to surgery and the various clinical and
      histological factors assessed. CONCLUSIONS: In our experience, the chance of
      identifying the sentinel node at the time of surgery does not increase with
      longer isotope injection duration using technetium99m antimony sulphide colloid.
      As soon as a sentinel node is identified at lymphoscintigraphy, one can proceed
      to surgery. Scanning beyond 3 h does not appear to be effective in sentinel node
      localization. Given that the median time for successful lymphoscintigraphic
      mapping was only 40 min, lymphoscintigraphy can easily be completed during the
      morning to allow surgery to take place the same day.

PMID- 12190725
TI  - Surgical strategies in the laparoscopic therapy of cholecystolithiasis and common
      duct stones.
AB  - BACKGROUND: The purpose of the present study was to examine the current approach
      and different strategies adopted for laparoscopic cholecystectomy in Germany.
      METHODS: A retrospective survey was conducted at 859 (n = 1200; 67.6%) hospitals
      in Germany. Data from 123 090 patients who had undergone cholecystectomy were
      analysed. RESULTS: 71.9% of the operations were finished laparoscopically (n = 88
      537) whereas 22.5% were carried out using the open technique. Conversion to open
      surgery was required in 7.1% of the laparoscopically started operations. When
      common bile duct stones were diagnosed preoperatively, 74.4% of the participants
      favoured the primary endoscopic extraction, following laparoscopic
      cholecystectomy. In cases of intraoperative diagnoses, laparoscopic
      cholecystectomy was finished and postoperative primary endoscopic extraction was
      carried out in more than half of the hospitals (58.4%). Sixteen per cent
      converted to an open operation with simultaneous exploration of the common duct.
      Laparoscopic desobstruction of the common bile duct was extremely rare (4.4%).
      Compared with open cholecystectomy, the results show a lower incidence of
      postoperative reinterventions (0.9 vs 1.8%) and fatal outcomes (0.04 vs 0.53%)
      for laparoscopic cholecystectomy. In contrast, common bile duct injuries were
      more frequent in the laparoscopic cholecystectomy group (0.32 vs 0.12%). The
      median duration of hospitalization was 6.1 days (range: 2.8-12) in the
      laparoscopic cholecystectomy group compared with 10.4 days (range: 3-28) in the
      open cholecystectomy group. CONCLUSIONS: Laparoscopic cholecystectomy is the
      standard procedure for the treatment of uncomplicated gallstone disease. There
      are reasonable differences between the hospitals in type of cholecystectomy for
      acute cholecystitis, management of common duct stones and intraoperative
      diagnostics in laparoscopic cholecystectomy, even after adjustment for
      differences in patient comorbidities.

PMID- 12190726
TI  - Influence of adhesive drapes on intraperitoneal volume and pressure during
      laparoscopy.
AB  - BACKGROUND: The influence of adhesive skin drapes on abdominal wall compliance
      during laparoscopy has not previously been studied. METHODS: The effect of
      removing an adhesive abdominal drape on intraperitoneal volume and pressure was
      studied in 15 patients undergoing a variety of laparoscopic procedures. The
      internal consistency of this data was evaluated by comparing the observed
      response to that which was predicted from analysis based on the theory of
      elasticity. RESULTS: Removal of an adhesive skin drape after induction of a 15
      mmHg pneumoperitoneum was associated with changes in intraperitoneal pressure and
      volume. These changes were statistically significant, highly predictable and
      clinically relevant. CONCLUSIONS: On the basis of the present observations, we
      recommend that extensive coverage by adhesive drapes should be avoided for those
      patients or procedures in which elevated intraperitoneal pressure may be
      particularly deleterious.

PMID- 12190728
TI  - Utilization of preoperative autologous blood donation in elective surgery.
AB  - BACKGROUND: The aim of the present paper was to review the pattern of collection
      and transfusion of autologous red cells for elective surgical procedures METHODS:
      Data on requests for preoperative autologous donation of blood were obtained from
      the Australian Red Cross Blood Service, Victoria and the Royal Melbourne Hospital
      for the calendar year 1998. The following information was collected: patient age,
      sex, surgery type, number of autologous units requested and collected and, if
      relevant, reasons for not achieving the requested collection. Transfusion of
      autologous units and any additional homologous units was confirmed from records
      at the blood banks of the Royal Melbourne Hospital and Melbourne Pathology (the
      pathology provider performing cross-matching for the majority of autologous units
      collected by Australian Red Cross Blood Service, Victoria). RESULTS: Over 12
      months, 2803 units of autologous blood were requested and 2282 units collected
      from 1301 patients. The most common reason for failure to collect the number of
      units requested was insufficient time between referral and surgery. Of the
      autologous units collected, 73% were transfused giving a collection to
      transfusion ratio of 1.4. Sixty-eight per cent of patients received their
      autologous units only, 10% received both autologous and homologous units, while
      22% were not transfused. For the majority of procedures, patients using
      preoperative autologous donation of blood had higher transfusion rates than those
      who did not use this. CONCLUSIONS: Ninety per cent of patients undergoing
      preoperative autologous donation of blood successfully avoided homologous blood
      exposure. However, preoperative autologous donation of blood is both wasteful and
      increases the incidence of transfusion in surgical procedures.

PMID- 12190729
TI  - Use of red blood cell transfusions in surgery.
AB  - BACKGROUND: Limited blood supplies necessitate the rational use of blood
      products. The aim of the present study was to provide a basis for audits of red
      cell usage in surgery by benchmarking common practice. Application of the data to
      the construction of a maximum surgical blood order schedule may be relevant for
      centres that perform a serological crossmatch or who collect autologous units.
      METHODS: Data on surgical procedures identified by Commonwealth Medical Benefits
      Schedule item numbers, were collected retrospectively from theatre and blood bank
      records at the Royal Melbourne and Melbourne Private hospitals from May 1997 to
      April 1998. The percentage of procedures for which red cells were transfused, and
      the mean, median and range of units transfused for procedures with >/= 30%
      transfusion likelihood were identified. RESULTS: Over 12 months, 266 surgical
      procedure codes were itemized >/= 10 times each, contributing 12 300 data
      entries. Only 38 procedures demonstrated an incidence of transfusion of at least
      30%. Most frequently transfused procedures included spinal fusion, total hip
      replacement, mandible/maxilla resection, prostatectomy and bladder excision.
      CONCLUSION: The number of common surgical procedures in which there is a 30% or
      greater likelihood that red cell transfusions will be given is limited. This
      benchmarking of common red cell usage is a first step in the process of
      determination of transfusion appropriateness.

PMID- 12190730
TI  - Baseline comparisons in surgical trials.
AB  - INTRODUCTION: Baseline measurements are an essential component of clinical
      trials. They should establish that the groups involved are clinically equivalent
      so that any observed differences can be attributed to the intervention under
      evaluation. The objective of this study was to review the use of baseline
      comparisons in surgical trials. METHODS: A standardized format was used to
      evaluate 206 surgical trials published within 10 prestigious journals between
      January 1997 and December 1999. RESULTS: One hundred and fifty-one (73%) of the
      trials used the first table in the article to record baseline data. More than one
      quarter of the trials declared less than five items and one-third of the trials
      inappropriately used 'P-values' as a measure of baseline equivalence. Only nine
      of the 54 multicentre studies (17%) mentioned the individual centres as possible
      confounding factors. DISCUSSION: Greater attention needs to be paid to baseline
      comparisons in surgical trials. One way of developing this type of critical
      ability is to use a checklist while reading a surgical trial of interest. Good
      resources include the CONSORT Statement by a group of prominent international
      biostaticians and the CLEAR (Critical Literature Evaluation and Research) Courses
      run by the Royal Australasian College of Surgeons.

PMID- 12190731
TI  - Does frozen section have a role in the intraoperative management of thyroid
      nodules?
AB  - BACKGROUND: Frozen section in thyroid surgery is used to make an intraoperative
      pathological diagnosis of malignancy in a thyroid nodule at the time of
      hemithyroidectomy. A positive diagnosis allows completion of thyroidectomy, thus
      avoiding reoperation. However, the use of fine needle aspiration cytology in
      making a preoperative diagnosis of cancer has resulted in the lack of a defined
      role for frozen section. We examined the role of frozen section as an adjunct to
      fine needle aspiration cytology in determining which cytological subset will
      benefit from frozen section. METHODS: All patients who underwent thyroidectomy
      between 1992 and 2000 by a single endocrine surgeon were reviewed. RESULTS: Two
      hundred and nine frozen sections were performed, of which 144 underwent
      preoperative fine needle aspiration cytology. Frozen sections reported 135 benign
      nodules, 59 follicular neoplasms, five specimens with suspicious histology and 10
      cancers. Ten out of 20 thyroid cancers were correctly identified by frozen
      section (sensitivity: 50%; specificity: 100%), eight cancers were reported on
      frozen section as indeterminate and two benign. Of 144 fine needle aspiration
      cytological procedures, frozen section on seven suspicious aspirates identified
      two cancers, and frozen section on 70 follicular aspirates identified four
      cancers, allowing intraoperative conversions to total thyroidectomy. Frozen
      section on seven malignant aspirates confirmed four cancers but resulted in
      reoperation for three because of the indeterminate frozen section reports. There
      were no cancers found on 135 benign aspirates. CONCLUSIONS: Frozen section on
      benign aspirates is unhelpful in the management of thyroid nodules. It need not
      be performed for cytologically proven malignant thyroid nodules. Selective use of
      frozen section complements fine needle aspiration cytology findings of suspicious
      or follicular lesions, especially in the subset with papillary cancer, allowing
      one-stage total thyroidectomy.

PMID- 12190732
TI  - Inguinal hernia repair: where to next?
AB  - BACKGROUND: Hernia repair is one of the most frequently performed operations in
      general surgery - a total of 39 000 elective inguinal hernia repairs were
      performed in public and private hospitals in Australia between July 1998 and June
      1999 - and, as such, even minor alterations in outcome and resource use have
      appreciable impact. However, decisions regarding choice of operation for hernia
      repair remain controversial. The purpose of the present paper is to critically
      evaluate the evidence available regarding recently introduced open mesh repair
      techniques and to try to identify meaningful directions for future hernia
      research. METHODS: A thorough search of all published surgical literature was
      undertaken. Medline, EMBASE and the Cochrane databases were searched by title, by
      key words and by author. References in review articles and in textbooks were
      pursued. The manufacturing companies were contacted for trials evaluating their
      product. RESULTS: Eight original articles evaluating either the Kugel Patch, the
      PerFix Plug or the Prolene Hernia System were located. None of these trials
      directly compared two or more of these repair systems. To date, there has been no
      published review of the evidence regarding the newer mesh repair techniques. With
      one exception, all of these articles qualify as Level IV evidence. Highlighted is
      the lack of evidence regarding chronic significant posthernioplasty pain - this
      has an incidence of 6-12%. This complication is 3-5 times more common than
      recurrence after open repair, is clinically relevant, is poorly understood and
      has been poorly studied. Arguably it is a more important end point than
      recurrence. CONCLUSION: Only one study comparing the newer techniques of open
      hernia repair (PerFix Plug) constitutes level II evidence. The PerFix Plug
      appears to be quicker to insert and uses a smaller incision. Chronic significant
      posthernioplasty pain is a more important endpoint in hernia research than is
      recurrence, and this review concludes with a proposal for a multicentre,
      randomized, controlled trial evaluating the incidence of chronic significant
      posthernioplasty pain following elective mesh repair of primary, unilateral 
      hernias.

PMID- 12190733
TI  - Issues of consent and privacy affecting the functioning of ASERNIP-S.
AB  - The Australian Safety and Efficacy Register for New Interventional Procedures -
      Surgical (ASERNIP-S) undertakes horizon scanning, systematic reviews and audits.
      By disseminating information derived from these processes, ASERNIP-S aims to
      improve the quality of health care. In the present article, we discuss some of
      the legal and ethical issues surrounding the collection of identified data for
      the purposes of audit. The individual's right to privacy is considered as well as
      the benefits of improving the quality of surgical health care.

PMID- 12190734
TI  - David Murray Morton: father figure of surgery at St Vincent's Hospital, bush
      lawyer and thwarted reformer of the medico-legal system.
AB  - When the first Golden Age of surgery at St Vincent's Hospital Melbourne (a period
      covering the first 25 years of the twentieth century) is discussed, the names
      that spring to mind are usually those of Sir Thomas Dunhill, Sir Hugh Devine, Sir
      Douglas Shields and Julian Smith. A name which is often overlooked, and by now
      almost forgotten, is that of David Murray Morton. Murray -Morton's career both as
      a medical student, general practitioner, anaesthetist and surgeon coincided with
      a revolution in the practice of medicine. He witnessed the progression from
      Listerian antisepsis to asepsis in surgical practice, the improvements in
      anaesthesia, the introduction of antibiotics and, before he died in 1959, the
      beginnings of organ transplants and open heart surgery. Morton was fond of saying
      that he grew up with the hospital. From the time of his first appointment as an
      anaesthetist in l896 to the time of his retirement from St Vincent's as senior
      surgeon in 1931, Morton, admired by all as a highly competent surgeon and a man
      of incorruptible probity, can rightly be described as the father figure of
      surgery during the formative years of St Vincent's Hospital. His innate sense of
      justice and fair play formed the basis of his distinguished tenure of the
      Presidency of the Medical Defence Association of Victoria, where his constructive
      attempts at reform of the medico-legal system were only thwarted by the
      predictable opposition of the legal profession and politicians.

PMID- 12190735
TI  - Electrolytic ablation as an adjunct to liver resection: Safety and efficacy in
      patients.
AB  - BACKGROUND: Electrolytic ablation is a relatively new method for the local
      destruction of colorectal liver metastases. Experimental work in animal models
      has shown this method to be safe and efficacious. However, before proceeding to
      clinical trials it was necessary to confirm these findings in a pilot study of
      five patients. METHODS: Five patients with colorectal liver metastases were
      studied prospectively. Each patient underwent a potentially curative liver
      resection. One of the metastases to be removed was treated using electrolysis
      before resection. Each patient was monitored closely during and after
      electrolysis to determine any morbidity associated with the treatment. Once
      resected, the metastases were examined histologically for completeness of
      ablation. RESULTS: All patients tolerated the electrolysis well; there were no
      deaths or complications related to the treatment. Histological examination of the
      resected metastases which had been treated electrolytically showed complete
      tissue destruction with no viable malignant cells remaining at the site of
      treatment. DISCUSSION: This pilot study of electrolytic ablation of liver
      metastases in five patients showed the treatment to be well tolerated and safe.
      Additionally, it demonstrated total destruction of the malignant tissue at the
      site of electrolysis. Based on these encouraging results, clinical trials can now
      begin.

PMID- 12190736
TI  - Why not use a small incision to treat large hydroceles?
AB  - BACKGROUND: Operative treatment of large hydroceles generally requires a large
      incision. METHODS: A technique is described which permits a traditional
      Jaboulay's or Lord's repair to be done through a 3 cm incision. RESULTS: Twenty
      patients with large hydroceles were operated on from June 2000 to November 2001
      using this technique and to date, only one patient has had a recurrence. There
      has been no occurrence of either scrotal wound infection or haematoma -formation.
      CONCLUSIONS: A hydrocele repair of the surgeon's choice can be done safely
      through a 3 cm incision.

PMID- 12190737
TI  - Study of serum calcium and trace elements in chronic cholelithiasis.
AB  - BACKGROUND: High biliary calcium and trace elements (copper, zinc and iron) in
      patients with chronic cholelithiasis can be associated with gallstones. METHODS:
      Estimations of calcium, copper, zinc and iron were done in the serum, gall
      bladder bile and gallstones of 48 patients with chronic cholelithiasis and in 20
      age- and sex-matched controls. Biliary levels of calcium and trace elements and
      bile/serum ratio of calcium and trace elements were compared in the two groups.
      RESULTS: Serum calcium was significantly less (P = 0.009) than controls, but
      biliary calcium was higher in the patients with chronic cholecystitis. All trace
      elements were found to be significantly higher (P </= 0.036) in the bile of
      patients with chronic cholelithiasis. The bile/serum ratio of calcium, copper and
      zinc was significantly greater (P </= 0.03) in patients of chronic
      cholelithiasis. Gall bladder bile in patients with chronic cholelithiasis was
      slightly more alkaline. Pigment stones contained significantly more calcium,
      copper and iron than cholesterol stones (P </= 0.001). CONCLUSION: Higher biliary
      calcium and trace elements as well as a defective pH of gall bladder bile in
      patients with chronic cholelithiasis could be the underlying factor in the
      pathogenesis of gallstones.

PMID- 12190738
TI  - CRASH trial: the first large-scale randomized controlled trial in head injury.

PMID- 12190739
TI  - Colon ischaemia from a stammers hernia: a long-term complication after Billroth
      II gastrectomy.

PMID- 12190740
TI  - Hydrocele of the canal of Nuck.

PMID- 12190741
TI  - Localized brainstem infarction presenting as acute onset dysphagia.

PMID- 12190742
TI  - Pseudotumour cerebri due to a Torcular epidermoid cyst.

PMID- 12190744
TI  - Optimal position for a cervical collar incision.

PMID- 12190743
TI  - Surface landmarks of the facial nerve trunk: a prospective measurement study.

PMID- 12190746
TI  - A new way of managing critical care?

PMID- 12190748
TI  - The use of anaesthetic rooms for induction of anaesthesia: a postal survey of
      current practice and attitudes in Great Britain and Northern Ireland.
AB  - A postal survey was sent to all anaesthetic departments in the UK to identify
      current practice and gain insight into anaesthetists' attitudes regarding the use
      of anaesthetic rooms for induction of general anaesthesia. Replies were received
      from 247 (88%) departments. Of these, 10 (4%) departments routinely anaesthetise
      all patients in theatre. The main reason for change was patient safety. Of those
      who routinely use the anaesthetic room for induction of anaesthesia, only 5% have
      made provision to change to in-theatre induction. An estimated pound 30 million
      has been spent on equipping anaesthetic rooms since 1994; with the result that
      91% of departments where anaesthetic room induction occurs, now have monitoring
      that complies with the current Association of Anaesthetists of Great Britain and
      Ireland guidelines. The majority of the respondents who use anaesthetic rooms
      perceived induction in theatre to result in reduced efficiency, increased patient
      anxiety, a worse teaching environment and no improvement in patient safety. This
      was in contrast to the attitudes of respondents from hospitals where in-theatre
      induction occurs. Only 9.7% of all respondents believed that clinical governance
      would necessitate a change to anaesthetizing all patients in theatre compared to
      25% who believed that the increasing costs of monitoring equipment would lead to
      a change. Overall 79% of respondents prefer to use the anaesthetic room, 16%
      prefer in-theatre induction and 5% expressed no preference. However, of those who
      routinely anaesthetise in theatre, 70% thought it to be preferable.

PMID- 12190747
TI  - Randomised controlled trial investigating the influence of intravenous fluid
      titration using oesophageal Doppler monitoring during bowel surgery.
AB  - Oesophageal Doppler monitoring allows non-invasive estimation of stroke volume
      and cardiac output. We studied the impact of Doppler guided fluid optimisation on
      haemodynamic parameters, peri-operative morbidity and hospital stay in patients
      undergoing major bowel surgery. Fifty-seven patients were randomly assigned to
      Doppler (D) or control (C) groups. All patients received intra-operative fluid
      therapy at the discretion of the non-investigating anaesthetist. In addition,
      Group D were given fluid challenges (3 ml x kg(-1)) guided by oesophageal
      Doppler. Group D received significantly more intra-operative colloid than Group C
      (mean 28 (SD 16) vs. 19.4 (SD 14.7) ml x kg(-1), p = 0.02). Cardiac output
      increased significantly for Group D whilst that of controls remained unchanged.
      The mean difference between the groups in final cardiac output was 0.87 l x min(
      1) (95% confidence interval 0.31-1.43 l x min(-1), p = 0.003). Five control
      patients required postoperative critical care admission. Fluid titration using
      oesophageal Doppler during bowel surgery can improve haemodynamic parameters and
      may reduce critical care admissions postoperatively.

PMID- 12190749
TI  - The effect of low dose sevoflurane on saccadic eye movement latency.
AB  - We investigated the effects of a low concentration of sevoflurane on a saccadic
      eye movement task that reflects the performance of higher neural decision and
      control mechanisms. The experiments were performed double-blind in five subjects,
      using either 0.15% end-tidal sevoflurane in oxygen, or pure oxygen as a placebo.
      Saccades were recorded and analysed using a computer-based recording system that
      also controlled the presentation of visual targets. Administration of oxygen
      produced no significant change in median latency compared with breathing air; but
      in four of the five subjects, administration of sevoflurane in oxygen caused a
      significant increase in latency. These results suggest that measurement of median
      saccadic latency may be a useful functional measurement of impairment of
      performance during recovery from anaesthesia.

PMID- 12190750
TI  - A randomised, controlled, crossover trial of oral midazolam and nitrous oxide for
      paediatric dental sedation.
AB  - A randomised, controlled, crossover trial was designed to assess the safety and
      effectiveness of oral midazolam sedation for orthodontic extractions. Forty-six
      ASA physical status I children aged 10-16 years were recruited. Each child
      required two treatment sessions. Sedation with either oral midazolam 0.5 mg.kg-1
      or nitrous oxide in oxygen was used at the first visit, the alternative being
      used at the second visit. Blood pressure, heart rate, arterial oxygen saturation,
      and sedation and behavioural scores were recorded every 5 min. Anxiety levels and
      postoperative satisfaction were also recorded. Blood pressure, heart rate and
      arterial oxygen saturation in both groups were similar and within acceptable
      clinical limits. The median [range] lowest arterial oxygen saturation levels for
      subjects in the midazolam and nitrous oxide groups were 95 [90-100]% and 98 [93
      100]%, respectively. The median [range] time to the maximum level of sedation in
      the midazolam group was 20 [5-65] min compared with 5 [5-10] min in the nitrous
      oxide group (p < 0.001). The median [range] duration of treatment was similar in
      both groups (midazolam group: 10 [5-30] min, nitrous oxide group: 10 [5-25] min).
      Seventy-four per cent of subjects were prepared to have oral midazolam sedation
      again, 54% preferring it. Oral midazolam appears to be a safe and acceptable form
      of sedation for 10-16-year-old paediatric dental patients.

PMID- 12190751
TI  - A randomised, controlled trial of cognitive and psychomotor recovery from
      midazolam sedation following reversal with oral flumazenil.
AB  - Flumazenil is traditionally administered intravenously to reverse the adverse
      effects of over sedation with benzodiazepines. The aim of this study was to test
      postoperative cognitive and psychomotor recovery from midazolam conscious
      sedation, following reversal with orally administered flumazenil. It was
      hypothesised that when administered by the oral route, flumazenil may enhance
      recovery over a prolonged period, thus increasing safety. Eighteen patients
      requiring intravenous midazolam sedation for dental treatment completed a
      randomised, double-blind, crossover trial. Following treatment the patients'
      sedation was reversed using either flumazenil or saline (as placebo),
      administered orally, on alternate appointments. Assessment of mood and cognitive
      function were undertaken using ClinPhone.cdr(R), a highly sensitive and specific
      computerised battery of cognitive tests administered by telephone prior to
      sedation and every hour for seven hours post reversal. Results indicate that
      within 20 min of administration, oral flumazenil is capable of partially
      reversing some cognitive and psychomotor impairments but the attentional and
      stimulus discrimination effects of midazolam sedation still remain.

PMID- 12190752
TI  - A comparison of anaesthetic techniques for shock wave lithotripsy: the use of a
      remifentanil infusion alone compared to intermittent fentanyl boluses combined
      with a low dose propofol infusion.
AB  - This study examined the intra-operative and postoperative characteristics of a
      remifentanil infusion alone, or intermittent fentanyl bolus admistration combined
      with a propofol infusion, for the anaesthetic management of patients undergoing
      shock wave lithotripsy. One of the key parameters investigated was the time to
      discharge. Fifty patients scheduled for extracorporeal shock wavelithotripsy
      (ESWL) were randomly allocated to receive either a continuous infusion of 0.2-0.4
      micro g.kg-1.min-1 of remifentanil (Group 1) or a bolus of 3 micro g.kg-1
      fentanyl followed by a continuous infusion of propofol at a rate of 2 mg.kg-1.h-1
      with additional boluses of 0.05 mg fentanyl administered as required (Group 2).
      Both anaesthetic techniques were found to provide satisfactory analgesia and
      intra-operative conditions for ESWL. However, patients in the remifentanil Group
      1 showed a higher incidence of nausea (52% vs. 0%, p < 0.01) and retching (36%
      vs. 0%, p < 0.01) 120 min following ESWL compared to Group 2. This resulted in
      prolonged discharge times (p < 0.01) in this group. We found that remifentanil
      used as the sole agent failed to demonstrate any advantage over the combination
      of fentanyl/propofol with regard to rapid recovery and discharge following
      anaesthesia for extracorporal shock wave lithotripsy.

PMID- 12190753
TI  - The Human Rights Act 1998: implications for anaesthesia and intensive care.
AB  - The Human Rights Act 1998 was incorporated into UK statutory law on October 2,
      2000. The 18 Articles of the Act are likely to have a significant impact on the
      practice of medicine in the UK, particularly in reference to consent, disclosure
      of medical information and patient access to healthcare. This article examines
      the implications of the new legislation for anaesthetic and intensive care
      practice.

PMID- 12190755
TI  - Evaluation of an expired fraction carbon dioxide monitor.
AB  - Respiratory monitoring is an important aspect of critical care, especially in
      neurosurgery and neuro-intensive care. Fixed capnographs are too cumbersome to
      allow monitoring during patient transport. Recently several portable expired
      fraction carbon dioxide devices have been developed, but no evaluation of their
      clinical peformance has been reported. We compared the Criticare POET LT Handheld
      expired fraction carbon dioxide monitor, in three different settings, to fixed
      capnographs and arterial blood gas analysis. A methodology for systematic
      appraisal of end-tidal capnographs is proposed.

PMID- 12190754
TI  - The peri-operative implications of herbal medicines.
AB  - An increasing number of patients are taking herbal medicines such as echinacea,
      garlic, ginkgo biloba, ginseng, St John's Wort, valerian, ephedra, kava,
      grapefruit juice and ginger. Although these herbal medications are considered
      'natural' products that may have some benefits, adverse effects such as increased
      bleeding tendencies and drug interactions are associated with their use. Surgeons
      and anaesthetists may be unaware of their patients' use of these medications
      because it is common for patients not to disclose their use of this form of
      medication, and both surgeons and anaesthetists often fail to enquire about their
      use. Anaesthetists and surgeons must be familiar with the effects of herbal
      medicines and should specifically enquire about the use of herbal medicines
      during pre-operative assessment. Currently available data suggest that all herbal
      medicines should be ceased 2 weeks before surgery.

PMID- 12190756
TI  - Calf compartment pressures in the Lloyd-Davies position: a cause for concern?
AB  - Lower limb compartment syndrome is a rare consequence of surgery where the
      lithotomy position is maintained for several hours. The aim of this study was to
      observe the effect of the lithotomy position on lower limb compartment pressure
      and blood flow to the lower limb in surgical patients having colorectal
      procedures. We prospectively studied 23 patients undergoing colorectal surgery
      requiring the lithotomy position and recorded lower limb compartment pressure,
      and the blood pressure in the upper and lower limbs. The lithotomy position led
      to a significant (p < 0.001) fall in blood pressure to the lower limb from 87 (SD
      16) mmHg to 67.9 (SD 12) mmHg and a significant (p < 0.001) rise in lower limb
      compartment pressure from 13 (SD 7) mmHg to 31 (SD 12) mmHg. These two effects
      compromise blood flow to the lower limb in long surgical procedures where the
      lithotomy position is required. Intermittently lowering the legs and restoring
      blood flow may prevent compartment syndrome developing.

PMID- 12190757
TI  - Effect of cricoid pressure on the ease of fibrescope-aided tracheal intubation.
AB  - We studied the reasons for difficulty with tracheal intubation over a fibrescope,
      and whether cricoid pressure facilitated intubation, in 50 patients. After
      induction of anaesthesia and neuromuscular blockade in 10 patients (phase 1), we
      attempted to clarify the reasons for difficulty in advancing a tracheal tube over
      an orally-inserted fibrescope, by observing through another fibrescope that was
      inserted nasally into the pharynx. In the next 40 patients (phase 2), we studied
      the effect of cricoid pressure on the success rate of tracheal intubation over
      the fibrescope. After a fibrescope (with a tracheal tube over it) had been
      inserted orally into the trachea, patients were randomly allocated to receive
      either criocoid pressure or sham pressure, and the success rate of intubation
      within 60 s was assessed. In phase 1, the tube was advanced into the trachea
      without difficulty in three of 10 patients. In the remaining seven patients, the
      tube impacted on the epiglottis in one patient and on the arytenoid cartilage in
      another two patients, and the tube migrated into the hypopharynx in the remaining
      four patients. In phase 2, tracheal intubation was successful within 60 s in
      seven of 21 patients (33%) without cricoid pressure, compared with 12 of 19
      patients (63%) when cricoid pressure was applied (95% CI for difference 2-59%; p
      = 0.04). We conclude that cricoid pressure facilitates fibrescope-aided tracheal
      intubation.

PMID- 12190758
TI  - Routine pre-operative blood testing: is it necessary?
AB  - In order to determine the value of routine pre-operative screening
      investigations, the medical notes of 100 patients undergoing elective surgical
      procedures under general anaesthesia were subject to prospective audit. Pre
      operative screening investigations (full blood count, urea and electrolytes and
      random glucose) were analysed in terms of frequency of abnormalities and whether
      or not the peri-operative management was changed when the result was abnormal.
      The frequency of results being present in the note at the time of operation and
      the costing of the tests was also examined. A total of 773 tests was performed of
      which 70 (9.1%) were abnormal. Peri-operative management was altered as a result
      of only two abnormal results (0.2%). Eight complications arose, none of which
      could have been predicted by the pre-operative screening tests. In only 57% of
      cases were the results present in the medical notes at the time of surgery. It is
      conservatively estimated that a saving of pound 50 000 per year could be made in
      our hospital alone by selective ordering of tests.

PMID- 12190759
TI  - Efficacy of the ProSeal laryngeal mask airway during manual in-line stabilisation
      of the neck.
AB  - The laryngeal mask airway has a potential role during cardiopulmonary
      resuscitation, but its placement becomes more difficult during manual in-line
      stabilisation of the neck, and the device cannot reliably prevent pulmonary
      aspiration. The ProSeal laryngeal mask airway has a theoretical advantage of
      reducing aspiration because of its drainage tube, but its ease of placement
      during stabilisation of the neck is unknown. We studied 20 patients to compare
      ease of placement and the sealing effect between the standard and ProSeal
      laryngeal mask airways. In a randomised cross-over fashion, after induction of
      anaesthesia and neuromuscular blockade, the standard and ProSeal laryngeal mask
      airways were placed in turn. Placement was significantly easier for the ProSeal
      laryngeal mask airway (successful at the first attempt in 16 patients and at the
      second attempt in the remaining four patients) than for the laryngeal mask airway
      (successful at the first attempt in 12 of 20 patients and at the second attempt
      in three patients, and failed (> two attempts) in the remaining five patients; p
      = 0.04). The airway pressure at which gas leaked around the device was greater
      for the ProSeal than the laryngeal mask airway (mean difference 5.8 cmH2O; 95% CI
      2.9-8.7 cmH2O; p = 0.0008).

PMID- 12190760
TI  - A dedicated intravenous cannula for postoperative use effect on incidence and
      severity of phlebitis.
AB  - A prospective, randomised, controlled clinical study was performed to compare the
      incidence and severity of postoperative peripheral venous thrombophlebitis
      associated with a single intravenous cannula used for both intra-operative and
      postoperative purposes, and two cannulae, one used intra-operatively and the
      other postoperatively. Sixty American Society of Anaesthesiologists (ASA)
      physical status I or II patients aged 18-65 years undergoing elective surgery
      were studied. The technique of cannula insertion was standardised. After surgery,
      the cannulation sites were examined daily by a blinded investigator for the
      presence and severity of thrombophlebitis using the Baxter Scale. The two groups
      were similar in terms of age, gender, weight, type and duration of surgical
      procedures, and drugs and fluids administered both intra-operatively and
      postoperatively. The proportion of patients that developed phlebitis was
      significantly less in the two cannulae group (26.1%) than in the single cannula
      group (63.3%) (p < 0.0001). The severity of phlebitis was greater in the single
      cannula group than in the two cannulae group. These results indicate that the use
      of a dedicated cannula for postoperative use decreases the incidence and severity
      of postoperative, peripheral, cannula-related phlebitis.

PMID- 12190761
TI  - Elderly anaesthesia as part of a multidisciplinary team.

PMID- 12190762
TI  - Delayed presentation of tracheo-oesophageal fistula following percutaneous
      dilatational tracheostomy.

PMID- 12190763
TI  - Percutaneous dilatational tracheostomy and tracheal ring rupture.

PMID- 12190764
TI  - Percutaneous tracheostomy and microlaryngeal tubes.

PMID- 12190765
TI  - Percutaneous tracheostomy with the PercuTwist technique not so easy.

PMID- 12190766
TI  - Margin of safety for the uncuffed tracheal tube.

PMID- 12190767
TI  - A case of airway obstruction.

PMID- 12190768
TI  - Pneumocoele following psoas compartment block.

PMID- 12190769
TI  - Respiratory arrest in a parturient following intrathecal administration of
      fentanyl and bupivacaine as part of a combined spinal-epidural analgesia for
      labour.

PMID- 12190770
TI  - Epidural fixation.

PMID- 12190771
TI  - Head-up tilt and subarachnoid block for Caesarean section.

PMID- 12190775
TI  - Giant cell arteritis and the ophthalmologist.

PMID- 12190777
TI  - Neovascular age-related macular degeneration and its relationship to antioxidant
      intake.
AB  - PURPOSE: Experimental and epidemiological studies suggest that low antioxidant
      intake may be associated with the occurrence of neovascular age-related macular
      degeneration (AMD). METHODS: We investigated this hypothesis further with a case
      control study involving 72 case and 66 control patients attending the
      Ophthalmology Department of the University Hospital in Nijmegen. Data were
      collected by interview on antioxidant intake (i.e. in fruit and vegetables),
      cigarette smoking, sunlight exposure and familial predisposition. Antioxidant
      intake was calculated according to the method described in the Framingham Eye
      Study. Logistic regression analysis was used to estimate odds ratios (OR) and 95%
      confidence intervals (CI). RESULTS: The prevalence rate of AMD in patients with
      low antioxidant intake and low lutein intake (dichotomized at the median value)
      was about twice as high as that in patients with high intake: OR = 1.7, 95% CI
      (0.8-3.7), and OR = 2.4, 95% CI (1.1-5.1). Further specification of intake data
      into quartiles of antioxidant intake and lutein/zeaxanthine intake showed a clear
      dose-response relationship. CONCLUSION: The effect of dietary antioxidants upon
      macular health warrants preventive studies.

PMID- 12190776
TI  - Visual improvement with corticosteroid therapy in giant cell arteritis. Report of
      a large study and review of literature.
AB  - OBJECTIVES: (1) To report the incidence and extent of visual improvement achieved
      by high-dose systemic corticosteroid treatment in eyes with visual loss due to
      giant-cell arteritis (GCA). (2) To understand the cause of the discrepancies
      between visual improvement revealed by routine visual acuity (VA) and by the
      central visual field in kinetic perimetry. (3) To review critically the
      contradictory literature on the effectiveness of corticosteroid therapy on visual
      recovery in GCA and to attempt to reconcile differences in the reported results.
      METHODS: Clinical data were collected systematically on 84 consecutive patients
      (114 eyes) with visual loss, all of whom had GCA confirmed by temporal artery
      biopsy and treated by us with high-dose systemic corticosteroid therapy. The
      patients were treated between 1974 and 1999 and data were compiled
      retrospectively. All patients underwent a detailed visual and ophthalmic
      evaluation at the initial visit and at every follow-up. This included visual
      field testing (with a Goldmann perimeter). All were treated with systemic
      corticosteroid therapy (intravenous followed by oral in 41 patients and oral only
      in 43 patients). RESULTS: Visual loss was due to anterior ischaemic optic
      neuropathy (91%), central retinal artery occlusion (10.5%), cilioretinal artery
      occlusion (10%), and/or posterior ischaemic optic neuropathy (4%), either alone
      or in different combinations. Improvement in both VA (>or= 2 lines) and central
      visual field was found in only five (4%) eyes of five patients (three treated
      with intravenous and two with oral steroid therapy). Improvement in VA >or= 2
      lines but not in the central visual field was found in seven eyes (in six
      patients). Visual improvement was seen in 7% of 41 patients treated initially
      with intravenous steroids versus 5% (p = 0.672) of 43 patients treated with oral
      steroids only. Comparison of patients with visual improvement in both VA and
      fields versus those with no improvement suggested a shorter interval (p = 0.065)
      between onset of visual loss and start of therapy in the improved patients.
      CONCLUSIONS: In our study, only 4% of eyes with visual loss due to GCA improved,
      as judged by improvement in both VA and central visual field (by kinetic
      perimetry and Amsler grid). The data also suggest that there is a better (p =
      0.065) chance of visual improvement with early diagnosis and immediate start of
      steroid therapy. Improvement in VA without associated improvement in the central
      visual field or Amsler grid may simply represent a learned ability to fixate
      eccentrically with more effective use of remaining vision: this factor could help
      explain a number of reported cases in the literature of improved VA after steroid
      treatment for GCA. To prevent further visual loss in either eye and for
      management of systemic manifestations of GCA, all patients must be treated on a
      long-term basis with adequate amounts of systemic corticosteroids.

PMID- 12190779
TI  - Radius and asphericity of the posterior corneal surface determined by corrected
      Scheimpflug photography.
AB  - PURPOSE: To obtain the shape of the posterior corneal surface in a healthy
      population, using Scheimpflug photography corrected for distortion due to the
      geometry of the Scheimpflug imaging system and the refraction of the anterior
      corneal surface. METHODS: The posterior corneas of 83 subjects, ranging in age
      from 16 to 62 years, were measured in the vertical meridian using corrected
      Scheimpflug photography. The aspherical shape of the anterior Corneal surface was
      also determined in conjunction with the correction of Scheimpflug images.
      RESULTS: The average radius of the anterior corneal surface was 7.87 +/- 0.27 mm
      (SD), while the average radius of the posterior corneal surface was 6.40 +/- 0.28
      mm (SD). The ratio between the posterior and the anterior radius of curvature was
      0.81 +/- 0.02. The asphericity of the anterior and the posterior corneal surfaces
      was 0.82 +/- 0.18 and 0.62 +/- 0.27, respectively. The asphericity of the
      posterior corneal surface decreased significantly with age. The
      posterior/anterior asphericity ratio is also dependent on age and was 0.98 +/-
      0.17 at 16 years of age and 0.53 +/- 0.30 at 62 years of age. CONCLUSION:
      Corrected Scheimpflug photography is an appropriate technique for measuring the
      radius and asphericity of the posterior corneal surface. The asphericity of the
      posterior corneal surface changes with age.

PMID- 12190778
TI  - Detection of retinal neovascularizations using 45 degrees and 60 degrees
      photographic fields with varying 45 degrees fields simulated on a 60 degrees
      photograph.
AB  - PURPOSE: To compare the effectiveness of one- and two-field 45 degrees and 60
      degrees fundus photography for detection of retinal neovascularizations (NVEs);
      to compare the detection of NVEs in macular 45 degrees fields centred on the
      fovea, between the fovea and the disc and with the nasal border along the nasal
      disc margin with that in standard 60 degrees one- and two-fields. METHODS: Two
      ophthalmologists assessed red-free, black and white screening and follow-up
      photographs of 58 out of a total 72 patients referred for treatment for NVEs over
      the 3 year period 1997-99. The assessment included analysis of the numbers, sizes
      and locations of NVEs identified in different photographic fields defined by a
      transparent grid placed over two standard 60 degrees fields. RESULTS: Testing of
      45 degrees macular fields disclosed 59/81 (73%), 50/81 (62%) and 64/81 (79%),
      respectively, of NVEs detected in a 60 degrees fovea-centred photograph. Kappa
      values for detecting at least one NVE, when present, were 0.62 (95% CI 0.40
      0.83), 0.38 (95% CI 0.19-0.57) and 0.83 (95% CI 0.62-0.99). The corresponding
      figures when compared with two-field 60 degrees photography were 59/111 (53%),
      50/111 (45%) and 64/111 (58%), respectively. One macula-centred 60 degrees field
      disclosed 81/111 (73%) of NVEs detected by 60 degrees two-field photography with
      an additional optic disc-centred field. Two-field 45 degrees photography
      disclosed 86/111 (77%) of NVEs detected by two-field 60 degrees photography. A
      total of 90% of NVEs detected in the optic disc-centred 60 degrees field only
      were also detected in the corresponding 45 degrees field. CONCLUSION: One-field
      45 degrees photography cannot be recommended as a screening method for diabetic
      retinopathy. Two-field 45 degrees photography (macula-centred and disc-centred
      fields) disclosed 77% of NVEs detected by the corresponding two-field 60 degrees
      photography.

PMID- 12190780
TI  - No evidence of association between GT/CA-repeat polymorphism in the GLC1A gene
      promoter and primary open-angle or exfoliation glaucoma.
AB  - PURPOSE: To investigate whether variants of the polymorphic GT/CA-repeat in the
      regulatory sequences of the gene for GLC1A are associated with glaucoma.
      Mutations in the protein coding region of this gene are known to cause juvenile
      autosomal dominant glaucoma and are also found in a subset of cases with primary
      open-angle glaucoma (POAG). METHODS: Samples were collected from 197 patients
      with exfoliation glaucoma and 157 patients with POAG as well as from 92 healthy
      blood donors. The variable repeat located 342 base pairs upstream of the
      translational initiation site, was analysed by polymerase chain reaction (PCR)
      and detected on an ABI 377 DNA sequencer. RESULTS: Five alleles were detected,
      ranging in size from 13 to 17 repeat units, the most common of which was 14
      repeat units. This was present in 63.7%, 66.6% and 61.4% of the two cohorts of
      cases and the control group, respectively. There was no significant difference in
      the distribution of the alleles between the control group and the two patient
      groups, respectively. CONCLUSION: The present investigation provides no evidence
      that the variable repeat located in the regulatory sequences of the glaucoma gene
      GLC1A is associated with the risk of developing POAG or exfoliation glaucoma.

PMID- 12190781
TI  - Photoreceptor survival in transplantation of autologous iris pigment epithelial
      cells to the subretinal space.
AB  - PURPOSE: To investigate photoreceptor survival in transplantation of non-cultured
      iris pigment epithelial (IPE) cells to the subretinal space in a prospective
      experimental study. METHODS: Upper iridectomies were carried out in the right
      eyes of 37 pigmented rabbits. Suspensions of freshly harvested autologous IPE
      cells (without culturing) were prepared and injected into the subretinal space of
      the same eye. Follow-up examinations were carried out using ophthalmoscopy and
      colour fundus photography. The rabbits were killed at 1, 2, 3 and 6 months,
      respectively, and the eyes examined with light and electron microscopy. RESULTS:
      On histological examination, the photoreceptor cells were found to be well
      preserved in grafted areas at 1-3 months. At 6 months, the photoreceptors
      generally disclosed a normal nuclear layer and long outer segments when overlying
      areas with single cells or clusters of transplanted IPE cells. Multilayers of
      cells in abundance, including native RPE cells and macrophages (stained with RAM
      11), particularly under microfolds of the neural retina, were occasionally
      associated with photoreceptor damage and nuclear drop out from the outer retinal
      layer. There was no inflammatory response in the choroid and the choriocapillaris
      remained patent. CONCLUSION: The experiments show that grafting freshly harvested
      autologous IPE cells to the subretinal space is feasible and that the
      photoreceptors generally survive for at least 6 months when overlying the
      transplanted areas. Multilayers of abundant cells in the subretinal space may
      induce adverse focal effects on adjacent photoreceptors.

PMID- 12190782
TI  - Octreotide reduces ischaemia-reperfusion injury in the retina.
AB  - PURPOSE: To investigate the role of octreotide on retinal lipid peroxidation and
      histopathological changes during ischaemia/reperfusion (I/R). METHODS: Three
      groups of seven pigmented guinea pigs each were formed. These represented a
      control group, an ischaemia group and an ischaemia/octreotide group. One eye of
      each animal was selected for histopathological evaluation and the other for
      biochemical assay. Bilateral pressure-induced retinal ischaemia was instigated
      for 90 min and was followed by 24 hours of reperfusion. Animals in the
      ischaemia/octreotide and ischaemia groups received either 10 micro g/kg of
      octreotide or saline, repeated five times at 6-hourly intervals, with the first
      dose administered 15 min prior to the ischaemic insult. Retinal malondialdehyde
      (MDA) levels and the thickness of the retinal layers were measured. These were
      compared with equivalent measurements of the control group. RESULTS: The mean MDA
      level increased in the ischaemia group (p < 0.01) but not in the octreotide group
      (p > 0.05). Significant increases in the thickness of the overall retina (p <
      0.01), inner retina (p < 0.05) ganglion cell layer (p < 0.01) inner plexiform
      layer (p < 0.01) and inner nuclear layer (p < 0.01) were observed in the
      ischaemia group. No significant difference in thickness was found in any of the
      layers in the ischaemia/octreotide group. CONCLUSION: Octreotide reduces the
      increases in retinal MDA levels and retinal thickness observed during I/R.

PMID- 12190783
TI  - Subretinal pigment dispersion following transpupillary thermotherapy for
      choroidal melanoma.
AB  - PURPOSE: To report the case of a patient who developed considerable subretinal
      pigment/debris dispersion following transpupillary thermotherapy (TTT). This type
      of tumour response is extremely rare with this relatively new therapeutic
      modality. METHODS: A 50-year-old man with a left juxtapapillary choroidal
      melanoma measuring 8 x 6 x 4.3 mm was treated with 810 nm diode laser TTT
      administered in two sessions. Spot size was 3 mm and the power setting was 450
      mW. RESULTS: Four months after the first treatment session, a considerable amount
      of pigment/debris was seen to have dispersed in the subretinal space,
      accumulating mainly in the macular area. Over a 12-month follow-up, the tumour
      showed progressive shrinkage without any change in the amount or location of the
      shed pigment/debris. No new tumour formation, recurrence or systemic metastases
      were detected. CONCLUSION: Subretinal pigment/debris dispersion is an unusual
      complication after TTT and requires close follow-up. There has been no short-term
      compromise on the life or visual acuity of this patient.

PMID- 12190791
TI  - How to study postoperative nausea and vomiting.
AB  - Anesthesiological journals are flooded by innumerable studies of postoperative
      nausea and vomiting (PONV). Nevertheless, PONV remains a continuing problem with
      an average incidence of 20-30%. This paper should provide essential information
      for the design, conduct, and presentation of these studies. It should also
      increase comparability among future studies and help clinicians in assessing and
      reading the literature on PONV. First, future studies should address new and
      relevant questions instead of repeatedly investigating prophylactically given
      antiemetics whose main results are predictable (e.g. already proven by meta
      analysis). Second, group comparability should be based on well-proven risk
      factors and a simplified risk score for predicting PONV. Endless listings of
      doubtful risk factors should be avoided. Third, a realistic sample size
      estimation should be performed, i.e. in most cases at least 100 patients per
      group are necessary. Fourth, nausea, vomiting and rescue medication should be
      recorded and reported separately with the corresponding incidences (and number of
      patients with these separate symptoms), and the main end-point should be PONV.
      The entire observation period should cover 24 h. Additional reporting of the
      early (0-2 h) and delayed (2-24 h) postoperative period is desirable and should
      consider single and cumulative incidences. Lastly, interpretation of results
      should take into account the study hypothesis, sources of potential bias or
      imprecision, and the difficulties associated with multiplicity of analysis and
      outcomes.

PMID- 12190792
TI  - Volume-targeted therapy of increased intracranial pressure: the Lund concept
      unifies surgical and non-surgical treatments.
AB  - Opinions differ widely on the various treatment protocols for sustained increase
      in intracranial pressure (ICP). This review focuses on the physiological volume
      regulation of the intracranial compartments. Based on these mechanisms we
      describe a protocol called 'volume-targeted' ('Lund concept') for treatment of
      increased ICP. The driving force for transcapillary fluid exchange is determined
      by the balance between effective transcapillary hydrostatic and osmotic
      pressures. Fluid exchange across the intact blood-brain barrier (BBB) is
      counteracted by the low permeability to crystalloids (mainly Na+ and Cl-)
      combined with the high osmotic pressure (5500 mmHg) on both sides of the BBB.
      This contrasts to most other capillary regions where the osmotic pressure is
      mainly derived from the plasma proteins (approximately 25 mmHg). Accordingly, the
      level of the cerebral perfusion pressure (CPP) is of less importance under
      physiological conditions. In addition cerebral intracapillary hydrostatic
      pressure (and cerebral blood flow) is physiologically tightly autoregulated, and
      variations in systemic blood pressure are generally not transmitted to these
      capillaries. If the BBB is disrupted, transcapillary water transport will be
      determined by the differences in hydrostatic and colloid osmotic pressure between
      the intra- and extracapillary compartments. Under these pathological conditions,
      pressure autoregulation of cerebral blood flow is likely to be impaired and
      intracapillary hydrostatic pressure will depend on variations in systemic blood
      pressure. The volume-targeted 'Lund concept' can be summarized under four
      headings: (1) Reduction of stress response and cerebral energy metabolism; (2)
      reduction of capillary hydrostatic pressure; (3) maintenance of colloid osmotic
      pressure and control of fluid balance; and (4) reduction of cerebral blood
      volume. The efficacy of the protocol has been evaluated in experimental and
      clinical studies regarding the physiological and biochemical (utilizing
      intracerebral microdialysis) effects, and the clinical experiences have been
      favorable.

PMID- 12190793
TI  - Guidelines for the practice of anesthesia in Norway.
AB  - Since the first version saw the light of day in 1991 the Guidelines have occupied
      a central position in the Norwegian practice of anesthesia. This document
      comprises part of the quality management documents held in the departments of
      anesthesia in Norwegian hospitals. If departments of anesthesia are unable to
      adhere to certain specific points in the Guidelines, it is recommended that this
      should be documented in writing. It has been stated by central governmental
      bodies and patients' insurance organizations that the Guidelines will be an
      important factor in medico legal cases, although it is not an obligatory legal
      document for hospital owners. It is our objective that the document will form the
      foundation for quality assurance work in the departments of anesthesia in Norway.
      The purpose of this document is to ensure a satisfactory standard for the
      practice of anesthesia in Norway. 'The Guidelines for the Practice of Anesthesia
      in Norway' (the Guidelines) is a series of recommended guidelines. The practice
      of anesthesia in this context includes general anesthesia, regional anesthesia,
      controlled sedation, postoperative monitoring, and other observations where
      anesthesia personnel are required. The Guidelines apply to all doctors, nurses,
      and other personnel undertaking the delegated practice of anesthesia. Deviations
      from the Guidelines should be explained and documented in every case. The
      Guidelines should be adhered to in medical emergencies as far as possible. The
      Guidelines must not be allowed to prevent the execution of immediate and
      lifesaving measures. The Guidelines should be revised at regular intervals so
      that it is up-to-date with current legislation and medical and technological
      developments and practice.

PMID- 12190794
TI  - On what are our end-of-life decisions based?
AB  - BACKGROUND: The incidence of withholding and withdrawing life support from the
      critically ill has increased in recent years. The aim of this study was to assess
      the degree of consistency between the weight assigned by intensivists to
      different determinants and their relation to end-of-life decisions, and to
      evaluate the current concepts in withholding or withdrawing intensive care in
      Nordic countries. METHODS: Forty-one intensivists from Nordic countries completed
      a questionnaire sent by e-mail: consistency between contributing factors and the
      decisions regarding 10 actual cases was evaluated by logistic regression analysis
      and by the classification (leave-one-out) method. Concepts in management after
      the withdrawal decision were also analyzed. RESULTS: The median (range) number of
      withdrawals per physician was four (range 0-10) out of 10 cases. No single factor
      was an independent covariant of all decisions made. The classification method
      revealed that approximately 70% only of decisions could be predicted correctly.
      Different actions taken after a decision to withdraw intensive care varied from
      9.8% (discontinuing ventilator therapy) to 97.6% (informing relatives).
      CONCLUSIONS: No generally accepted grounds for end-of-life decisions could be
      detected among Nordic intensivists. In addition, the current concept of
      management after decision to withdraw therapy varies markedly. This study has
      implications in further assessment of the individual decision-making process and
      the uniformity of actions after withdrawal decisions.

PMID- 12190795
TI  - Plasma exchange in severe postpartum HELLP syndrome.
AB  - We present a case of extremely severe postpartum HELLP (hemolysis, elevated liver
      enzymes, low platelets) syndrome, associated with activation of coagulation,
      massive recurrent intra-abdominal bleeding requiring two laparotomies, renal
      failure, and central nervous system symptoms. This case underlines the complexity
      of pregnancy-related thrombotic microangiopathies regarding their differential
      diagnosis, multiple organ dysfunction, as well as management. Systemic
      endothelial cell injury plays a central role in the pathogenesis of thrombotic
      microangiopathies. Treatment of HELLP syndrome usually consists of administration
      of antihypertensive therapy and magnesium sulfate. No consensus exists regarding
      the use of plasma exchange or corticosteroids. Plasma exchange was a major part
      of the treatment regime in our patient. Early plasma exchange may be considered
      as an adjuvant therapy in severe and progressive postpartum HELLP syndrome.

PMID- 12190796
TI  - Immune response in asymptomatic smokers.
AB  - BACKGROUND: It has been demonstrated that cigarette smoking affects the immune
      system. Impairment of alveolar mononuclear cell function, described previously,
      may contribute to the higher rate of postoperative respiratory infections.
      However, increased susceptibility of smokers to infections of other origin (e.g.
      wound-related) implies that tobacco effect is not restricted to the respiratory
      immune competent cells. The present study was designed to investigate the
      systemic effect of tobacco smoking as it exerted on blood-derived immune cells.
      We measured systemic cytotoxic activity of natural killer cells, production of
      pro- and anti-inflammatory cytokines by blood mononuclear cells and their
      proliferation in response to mitogens. To minimize the immunosuppressive effect
      of other smoke-related factors, the smokers with chronic obstructive pulmonary
      disease (COPD) were excluded from this study. METHODS: Peripheral blood
      mononuclear cells (PBMC) from 24 chronic asymptomatic smokers, and 28 controls,
      age and gender matched, were isolated and incubated in vitro with
      lipopolysaccharide (LPS) or phytohemagglutinin (PHA) to induce secretion of IL
      1beta, IL-1ra, IL-6, IL-10, TNFalpha and IL-2, respectively, from mononuclear
      cells. The level of the cytokines in the supernatants was measured using ELISA
      kits. The proliferative response to the mitogens PHA and concanavalin A (ConA)
      was evaluated by 3H-thymidine incorporation and NK cell cytotoxicity by 51Cr
      release assay. RESULTS: Mononuclear cells from smokers showed increased
      production of the pro-inflammatory cytokines IL-1beta, IL-6 and TNFalpha and
      enhanced proliferative response to mitogens as compared to non-smoking
      population. The secretion of IL-2 and the anti-inflammatory cytokines IL-1ra and
      IL-10 was similar in both groups. NK cell cytotoxic activity was suppressed in
      the smokers. CONCLUSION: Cigarette smokers without chronic obstructive pulmonary
      disease (COPD) exhibit impaired NK cytotoxic activity in peripheral blood and
      unbalanced systemic production of pro- and anti-inflammatory cytokines. These
      changes may serve as predisposing factors for respiratory and systemic infections
      in the postoperative period and should alert an anesthetist during perioperative
      management.

PMID- 12190797
TI  - Comparison of forced-air warming systems with upper body blankets using a copper
      manikin of the human body.
AB  - BACKGROUND: Forced-air warming with upper body blankets has gained high
      acceptance as a measure for the prevention of intraoperative hypothermia.
      However, data on heat transfer with upper body blankets are not yet available.
      This study was conducted to determine the heat transfer efficacy of eight
      complete upper body warming systems and to gain more insight into the principles
      of forced-air warming. METHODS: Heat transfer of forced-air warmers can be
      described as follows: Qdot;=h. DeltaT. A, where Qdot;= heat flux [W], h=heat
      exchange coefficient [W m-2 degrees C-1], DeltaT=temperature gradient between the
      blanket and surface [ degrees C], and A=covered area [m2]. We tested eight
      different forced-air warming systems: (1) Bair Hugger and upper body blanket
      (Augustine Medical Inc. Eden Prairie, MN); (2) Thermacare and upper body blanket
      (Gaymar Industries, Orchard Park, NY); (3) Thermacare (Gaymar Industries) with
      reusable Optisan upper body blanket (Willy Rusch AG, Kernen, Germany); (4)
      WarmAir and upper body blanket (Cincinnati Sub-Zero Products, Cincinnati, OH);
      (5) Warm-Gard and single use upper body blanket (Luis Gibeck AB, Upplands Vasby,
      Sweden); (6) Warm-Gard and reusable upper body blanket (Luis Gibeck AB); (7)
      WarmTouch and CareDrape upper body blanket (Mallinckrodt Medical Inc., St. Luis,
      MO); and (8) WarmTouch and reusable MultiCover trade mark upper body blanket
      (Mallinckrodt Medical Inc.) on a previously validated copper manikin of the human
      body. Heat flux and surface temperature were measured with 11 calibrated heat
      flux transducers. Blanket temperature was measured using 11 thermocouples. The
      temperature gradient between the blanket and surface (DeltaT) was varied between 
      8 and +8 degrees C, and h was determined by linear regression analysis as the
      slope of DeltaT vs. heat flux. Mean DeltaT was determined for surface
      temperatures between 36 and 38 degrees C, as similar mean skin surface
      temperatures have been found in volunteers. The covered area was estimated to be
      0.35 m2. RESULTS: Total heat flow from the blanket to the manikin was different
      for surface temperatures between 36 and 38 degrees C. At a surface temperature of
      36 degrees C the heat flows were higher (4-26.6 W) than at surface temperatures
      of 38 degrees C (2.6-18.1 W). The highest total heat flow was delivered by the
      WarmTouch trade mark system with the CareDrape trade mark upper body blanket
      (18.1-26.6 W). The lowest total heat flow was delivered by the Warm-Gard system
      with the single use upper body blanket (2.6-4 W). The heat exchange coefficient
      varied between 15.1 and 36.2 W m-2 degrees C-1, and mean DeltaT varied between
      0.5 and 3.3 degrees C. CONCLUSION: We found total heat flows of 2.6-26.6 W by
      forced-air warming systems with upper body blankets. However, the changes in heat
      balance by forced-air warming systems with upper body blankets are larger, as
      these systems are not only transferring heat to the body but are also reducing
      heat losses from the covered area to zero. Converting heat losses of
      approximately 37.8 W to heat gain, results in a 40.4-64.4 W change in heat
      balance. The differences between the systems result from different heat exchange
      coefficients and different mean temperature gradients. However, the combination
      of a high heat exchange coefficient with a high mean temperature gradient is
      rare. This fact offers some possibility to improve these systems.

PMID- 12190798
TI  - Extubation after breathing trials with automatic tube compensation, T-tube, or
      pressure support ventilation.
AB  - BACKGROUND: Automatic tube compensation (ATC) is a new option to compensate for
      the pressure drop across the endotracheal or tracheostomy tube (ETT), especially
      during ventilator-assisted spontaneous breathing. While several benefits of this
      mode have so far been documented, ATC has not yet been used to predict whether
      the ETT could be safely removed at the end of weaning, from mechanical
      ventilation. METHODS: We undertook a systematic trial using a randomized block
      design. During a 2-year period, all eligible patients of a medical intensive care
      unit were treated with ATC, conventional pressure support ventilation (PSV, 5
      cmH2O), or T-tube for 2-h. Tolerance of the breathing trial served as a basis for
      the decision to remove the endotracheal tube. Extubation failure was considered
      if reintubation was necessary or if the patient required non-invasive ventilatory
      assistance (both within 48 h). RESULTS AND CONCLUSIONS: After the inclusion of 90
      patients (30 per group) we did not observe significant differences between the
      modes. Twelve patients failed the initial weaning trial. However, half of the
      patients who appeared to fail the spontaneous breathing trial on the T-tube, PSV,
      or both, were successfully extubated after a succeeding trial with ATC.
      Extubation was thus withheld from four and three of these patients while
      breathing with PSV or the T-tube, respectively, but to any patient breathing with
      ATC. It seems that ATC can be used as an alternative mode during the final phase
      of weaning from mechanical ventilation. Furthermore, this study may promote a
      larger multicenter trial on weaning with ATC compared with standard modes.

PMID- 12190799
TI  - Accuracy of point-of-care-testing (POCT) for determining hemoglobin
      concentrations.
AB  - BACKGROUND: While point-of-care testing (POCT) is being used increasingly as a
      basis for deciding on perioperative erythrocyte transfusion, no valid standards
      currently exist concerning the accuracy of Hb concentration measurements. For
      clinical employment, however, the confidence limits (+/-2 SD) of these
      measurements should lie close to 5 g/l. The aim of the present study was to
      evaluate the accuracy and precision of point-of-care testing for blood hemoglobin
      concentration (cHb in g/l) measurements in critically ill patients. METHODS:
      Fifty blood samples from 50 postoperative patients requiring intensive care
      treatment were withdrawn from a cannula in the radial artery into a 2-ml
      heparinized syringe (containing wet sodium heparinate in the conus), in a 2-ml
      Monovette with 50 IE lithium heparinate, and into a 2.7-ml cuvette with 1.6 mg
      potassium EDTA/ml blood. The POCT battery consisted of two blood gas analyzers
      (ABLTM 625 and 725, Radiometer, Copenhagen), the HemoCue system (Mallinckrodt
      Medical, Germany), and an automated hematology analyzer (M-2000(R), Sysmex,
      Germany). The cyanmethemoglobin method served as the reference 'gold standard'
      procedure. The blood gas analyzer and HemoCue systems were tested using dry and
      wet heparinized blood samples. RESULTS: Hemoglobin concentrations of the
      reference measurements ranged from 73.9 to 159.4 g/l. The automated hematology
      analyzer method did reveal a small but systematic deviation for higher cHb
      values. For the blood gas analyzer and HemoCue system procedures there was no
      systematic deviation of bias for either the first measurement or the averaged
      data. Bland & Altman analysis revealed a larger scattering for the wet
      heparinized samples. CONCLUSIONS: The above-stated requirement for POCT systems,
      i.e. that the confidence limits should lie close to 5 g/l cHb, held true for the
      dry heparinized samples of the blood gas analyzer (1st measurement and mean of
      2), the HemoCue system (mean of 3) and the automated hematology analyzer.

PMID- 12190800
TI  - Prostaglandin E1 at clinically relevant concentrations inhibits aggregation of
      platelets under synergic interaction with endothelial cells.
AB  - BACKGROUND: The inhibitory effect of prostaglandin E1 (PGE1) on platelet
      aggregation is considered an important characteristic of this agent. However, the
      concentration of PGE1 to inhibit aggregation in vitro is higher than those of
      clinical use (1 ng/ml). To clarify whether PGE1 at clinically relevant
      concentrations inhibits aggregation under synergic action with endothelial cell
      derived factors (nitric oxide and prostacyclin), we evaluated the minimum
      effective concentration of PGE1 to enhance the anti-aggregating activity of
      endothelial cells. METHODS: Inhibitory effects of PGE1 and/or the incubation
      buffer from cultured porcine aortic endothelial (PAE) cells on human platelet
      aggregation induced by 2 micro g/ml collagen were examined by turbidimetry.
      RESULTS: PGE1 concentration-dependently (>3 ng/ml) inhibited aggregation: the
      incubation buffer from PAE cells stimulated by bradykinin also inhibited
      aggregation. Bradykinin concentration-dependently increased the anti-aggregating
      activity of the PAE incubation buffer. The half-maximum effective concentration
      of bradykinin to inhibit aggregation (95.4+/-22.3 nM) was significantly decreased
      to 10.3+/-2.5 nM by 0.1 ng/ml PGE1 and to 0.9+/-0.5 nM by 1 ng/ml PGE1,
      respectively. These indicated that PGE1 (=0.1 ng/ml) inhibits aggregation through
      synergism with endothelial cells. The synergic effect of PGE1 and the anti
      aggregating activity of the PAE cells preincubated with 10 micro M indomethacin
      for 30 min was more potent than that of these cells preincubated with 1 mM NG
      nitro-L-arginine methyl ester. This suggested that the interaction of PGE1 with
      endothelial cell-derived nitric oxide is more powerful than that with endothelial
      cell-derived prostacyclin. CONCLUSION: Prostaglandin E1 (=0.1 ng/ml) inhibited
      platelet aggregation under synergic interaction with endothelial cells.

PMID- 12190801
TI  - Classification for coding procedures in the intensive care unit.
AB  - BACKGROUND: There is no commonly accepted coding system for non-operative
      procedures in general, including intensive care unit (ICU) procedures. In order
      to create a classification of codes for ICU procedures, a system developed at the
      University Hospital of Bergen was evaluated in four Nordic countries. METHODS:
      Classification codes were constructed using seven main groups of related
      procedures that were given a letter from A to G. Within each group major
      procedures were given a number from 00 to 99, with the possibility of up to 10
      subclassifications within each procedure. A simple questionnaire regarding the
      use of coding general ICU procedures and some specific procedures was sent to 171
      ICUs in Sweden, Finland, Denmark, and Norway. They were also asked to give their
      comments on the new classification coding system, which was attached. RESULTS:
      One hundred and fifty-four questionnaires were returned (response rate 90%). Some
      or most of the ICU procedures were registered in the ICUs (82.2%). However 38%
      did not use any coding system and 24% used a specific internal system. The new
      classification coding system was well received, and was given a mean value of 7.5
      using a VAS scale from 0 to 10 (best). Most ICUs would consider using this system
      if introduced at a national level. CONCLUSION: Most Nordic ICUs do register some
      or most of the procedures performed. Such procedures are however, registered in
      very different ways, using several different systems, and are often home-made.
      The new classification system of ICU procedures was well rated.

PMID- 12190802
TI  - Acetylcholine receptor density in human cricopharyngeal muscle and pharyngeal
      constrictor muscle.
AB  - BACKGROUND: Upper esophageal sphincter resting tone is reduced during partial
      neuromuscular block, whereas contraction of the pharyngeal constrictor muscle is
      only slightly affected. We hypothesized that this difference may arise from
      differential nicotinic acetylcholine receptor (nAChR) density, the density
      supposedly being lower in the more sensitive cricopharyngeal muscle than in the
      resistant pharyngeal constrictor muscle. The aim of this study was to determine
      the density of nAChR in the main component of the upper esophageal sphincter, the
      cricopharyngeal muscle, and in the pharyngeal constrictor muscle. METHOD: After
      approval by the institutional ethics committee and informed consent, muscle
      specimens were obtained from five patients undergoing surgery with laryngectomy
      for malignancies of the larynx or thyroid gland. None had received radiation
      therapy to the affected area. The nAChR from these tissue specimens were
      solubilized and incubated with 125I-alpha-bungarotoxin. The quantity of
      radioligand-receptor complex was measured by radioactive decay in a liquid
      scintillation counter. The receptor density was expressed as femtomoles per
      milligram of protein (fmol/mg protein). RESULTS: The nAChR density was determined
      to 6.8 (3.5) fmol/mg protein (mean (SD)) in the cricopharyngeal muscle and 5.6
      (2.1) fmol/mg protein in the pharyngeal constrictor muscle (P = 0.22). Although
      we could not find any difference in mean nAChR density, contrary to our
      hypothesis, the density in four of the five patients was higher in the
      cricopharyngeal muscle than in the pharyngeal constrictor muscle. CONCLUSION: Our
      results indicate that the density of nicotinic acetylcholine receptors is similar
      in the cricopharyngeal muscle and in the pharyngeal constrictor muscle. Nicotinic
      acetylcholine receptor density, as determined by 125I-alpha-bungarotoxin assay,
      cannot explain the difference in response to neuromuscular blocking drugs between
      the investigated muscles.

PMID- 12190803
TI  - Design evaluation of commonly used rigid and levering laryngoscope blades.
AB  - BACKGROUND: The shape of a laryngoscope blade affects the exposition of the
      larynx. This study evaluates and compares some rigid and levering blade designs
      based on previous investigative X-ray laryngoscopic studies. METHODS: Five rigid
      laryngoscope blades (Miller #3, Standard Macintosh #3, Classical Macintosh #4 and
      English-Macintosh #3 and #4) and two levering laryngoscope blades (McCoy in
      neutral and maximally elevated positions and Flexiblade in three basic positions:
      straight, neutral, and maximally curved) were evaluated. This study assesses two
      parameters derived from the depth of insertion: the eye line deviation from the
      ideal straight view line to the vocal cords, and the space occupied by the blade
      behind the mandible, which affects the contact of the blade tip with the base of
      the tongue. RESULTS: The best results on larynx exposition were produced by the
      English-Macintosh #4 at all insertion depths between 5 and 14 cm. It surpassed
      the Classical Macintosh #4 and both the English and Standard Macintosh #3.
      Although the Miller and the Flexiblade in a straight position afford a nearly
      ideal view line, both blades reduce the space reserved for the tongue behind the
      mandible. The McCoy with its tip maximally elevated provides limited view, while
      activation of the Flexiblade provides various ranges of larynx exposition.
      CONCLUSION: The difference in shape and design of Macintosh blades affects their
      performance. The distal portion of a large-sized curved blade is more effective
      than the full length of a shorter blade. The #4 English Macintosh is a better
      choice for routine clinical use. The Flexiblade performs as a multiblade device
      and can therefore be used for both routine and difficult intubations.

PMID- 12190804
TI  - Target-controlled infusion of propofol induction with or without plasma
      concentration constraint in high-risk adult patients undergoing cardiac surgery.
AB  - BACKGROUND: Calculated plasma (Cp) and calculated effect site concentrations (Ce)
      of propofol associated with loss of consciousness (LOC) have been studied in
      young healthy patients. The aim of the study was to evaluate the calculated
      propofol concentrations required to induce LOC in ASA III adult patients
      undergoing cardiac surgery using a smooth target controlled infusion of propofol.
      METHODS: After informed consent, 44 patients were premedicated with 0.5 mg
      alprazolam orally. Propofol TCI using the pharmacokinetic set of Marsh et al.
      incorporated in the Diprifusor (ThalfKeo of 2.6 min) was used. Propofol Ce was
      progressively increased by 0.5 micro g/ml until LOC was obtained. The constraint
      on the maximum gradient between Cp and Ce was either 1 micro g/ml in group 1 or
      not limited in group 2. Hemodynamic variations were assessed. RESULTS: Mean
      preoperative left ventricular ejection fractions were 44 +/- 15.4% and 56 +/-
      11.4% in groups 1 and 2, respectively (P < 0.01). At LOC, mean Cp was 1.9 micro
      g/ml in both groups but mean Ce was 1.08 +/- 0.31 and 1.43 +/- 0.42 micro g/ml in
      groups 1 and 2, respectively (P < 0.01). The mean induction time was 12.8 +/- 7.1
      min in group 1 and 8.5 +/- 2.7 min in group 2 (P < 0.05). No episode of
      hypotension has been observed in either group. CONCLUSION: In ASA III patients
      undergoing cardiac surgery, smooth propofol TCI induction, using the
      pharmacokinetic set of Marsh et al. incorporated in the Diprifusor, is associated
      with LOC at a low mean calculated plasma concentration of 1.9 micro g/ml and good
      hemodynamic stability.

PMID- 12190805
TI  - Sevoflurane low-flow anaesthesia: best strategy to reduce Compound A
      concentration.
AB  - BACKGROUND: To define the best strategy to reduce Compound A production in
      Sevoflurane low-flow anaesthesia by experiments in vitro and in vivo of different
      absorbers and different anaesthesia machines. METHODS: In vitro Compound A has
      been measured at 45 degrees C in vitro following Sevoflurane interactions with
      potassium hydroxide, sodium hydroxide, soda lime, Dragersorb 800 Plus and Amsorb,
      a new absorber that does not contain sodium or potassium hydroxide. In vivo
      Compound A concentration in the anaesthesia circuit (inspiratory branch) has been
      measured using an indirect sampling method through absorber vials (SKC) with
      active coal granules, during low flows (500 ml/min) general anaesthesia using
      soda lime, Dragersorb 800 Plus or Amsorb as absorber. Compound A was also
      measured during low flows (500 ml/min) general anaesthesia using as carbon
      dioxide absorber soda lime with different anaesthesia machines. RESULTS: In vitro
      at 45 degrees C Compound A concentration with soda lime and Dragersorb 800 Plus
      was about 10 times higher than with Amsorb. In vivo the Compound A concentrations
      in the inspiratory branch of the circuit were lower in the group with Amsorb.
      CONCLUSION: The Compound A production is minimal with Amsorb as carbon dioxide
      absorber.

PMID- 12190806
TI  - Effect of pretreatment with ketorolac on propofol injection pain.
AB  - BACKGROUND: : Pain on injection is still a major problem with propofol. We
      performed this study to compare different doses of intravenous (i.v.) ketorolac
      with and without venous occlusion and its effect on the incidence and the
      severity of the pain after propofol injection. METHODS: We conducted a
      prospective, randomized and double-blind study of 180 patients (20-60 years of
      age.) scheduled to undergo elective surgery. Six groups of patients were
      generated: group A received normal saline (NS) 2 ml i.v.; groups B, C, D received
      ketorolac 10 mg in 2 ml NS with venous occlusion (VO) and a subsequent propofol
      injection at either 30, 60 or 120 s; groups E and F received ketorolac 15 mg and
      30 mg in 2 ml NS and propofol was injected after 60 s. The pain perception was
      assessed during injection of propofol in all patients. RESULT: : The incidence of
      propofol-associated injection pain was for A: 46.7%; B: 43.4%; C: 23.3%; D:16.7%;
      E: 20%, and F: 10%. The incidence of pain following propofol injection was
      reduced by i.v. ketorolac 10 mg with venous occlusion for 120 s. Furthermore,
      i.v. ketorolac 15 mg and 30 mg but not 10 mg following propofol injection after
      60 s without venous occlusion revealed significant pain reduction when compared
      to saline group. There was no difference in venous sequelae at 7 days
      postoperatively between the groups. CONCLUSION: Our results suggested that
      pretreatment with i.v. 15 and 30 mg ketorolac reduces pain following propofol
      injection. Moreover, pretreatment with i.v. ketorolac 10 mg with venous occlusion
      for 120 s achieves the same pain relief effect.

PMID- 12190807
TI  - A comparative study on the analgesic effect of tramadol, tramadol plus magnesium,
      and tramadol plus ketamine for postoperative pain management after major
      abdominal surgery.
AB  - BACKGROUND: We tested whether, after major abdominal surgery, the addition of
      magnesium or ketamine to tramadol for intravenous (IV) patient-controlled
      analgesia (PCA) improved analgesia and lowered pain scores, compared to a PCA
      containing only tramadol. METHODS: Sixty-six patients were allocated randomly to
      receive a PCA with tramadol alone (T), tramadol plus magnesium (TM) or tramadol
      plus ketamin (TK), in a double-blind randomized study. Postoperative analgesia
      was started when the verbal rating scale (VRS) score was 2 or more. Following a
      loading dose of the study solution (which contained 1 mg/kg tramadol), a
      background infusion of 0.4 mg/kg/h was started. Patients were allowed to use
      bolus doses of 0.2 mg/kg every 20 min without a time limit. Discomfort, sedation,
      pain scores, total and bolus PCA tramadol consumption, and side-effects, were
      recorded for up to 24 h after the start of PCA. RESULTS: Pain and discomfort
      scores were lower (P < 0.01) in groups TM and TK at 15, 30, 60 and 120 min than
      in group T. The addition of magnesium or ketamine significantly reduced the
      consumption of tramadol at 6, 12 and 24 h (P < 0.01). The incidence of nausea did
      not differ between the groups. CONCLUSION: Adding magnesium or ketamine to
      tramadol improved analgesia and patient comfort and decreased the amount of
      tramadol required for postoperative pain management after major abdominal
      surgery.

PMID- 12190808
TI  - Interscalene brachial plexus block is superior to subacromial bursa block after
      arthroscopic shoulder surgery.
AB  - BACKGROUND: Arthroscopic shoulder surgery is often associated with severe
      postoperative pain. The results concerning subacromial bursa blockade (SUB) as a
      method of pain relief have been contradictory. We hypothesized that a SUB and
      interscalene brachial plexus block (ISB) would similarly reduce early
      postoperative pain and the need for oxycodone as compared to placebo (PLA).
      METHODS: Forty-five patients scheduled for arthroscopic shoulder surgery were
      enrolled in this randomised, prospective study. The ISB and SUB blockades were
      performed with 15 ml of ropivacaine (5 mg/ml). In the PLA group, 15 ml of 0.9%
      saline was injected into the subacromial bursa. All patients received general
      anaesthesia. RESULTS: The mean intravenously patient-controlled delivered
      oxycodone consumption during the first 6 h was significantly lower in the ISB
      group (6 mg) than in the SUB group (24.1 mg; P=0.001) or in the PLA group (27 mg;
      P<0.001). No significant differences were detected between the SUB and PLA groups
      (P=0.791). The postoperative pain scores during the first 4 h at rest and during
      the first 6 h on movement were significantly lower in the ISB group than in the
      SUB and PLA groups. CONCLUSION: After arthroscopic shoulder surgery SUB has a
      minor effect only on postoperative analgesia, whereas an ISB with low-dose
      ropivacaine effectively relieves early postoperative pain and reduces the need
      for opioids.

PMID- 12190809
TI  - Thoracic sympatholysis with epidural blockade assessed by quantitative
      measurement of cutaneous blood flow.
AB  - BACKGROUND: Quantifying sympathetic activity is difficult. Direct measurement is
      possible and superior to indirect techniques, but nerves to internal organs are
      not accessible in humans. Recently, we validated a quantitative technique for
      measurement of cutaneous blood flow using heat as an indicator. The aim of the
      study was to investigate whether sympatholysis during thoracic epidural blockade
      (TEA) may be documented by changes in regional cutaneous blood flow. A secondary
      aim was to assess whether, during TEA, local heating itself enhances regional
      blood flow. METHODS: Six patients scheduled for elective coronary artery bypass
      grafting (CABG) were studied. An epidural catheter was inserted at the T2-3
      interspace. Measurements were performed with an electrode, which can measure the
      local temperature of the skin. The probe is covered with a thermostatically
      controlled cap to avoid a thermic gradient to air. As a result of the cap, a
      change in temperature of the central disc depends almost solely on the blood flow
      in the underlying tissue. Regional cutaneous blood flow rates were measured
      before and after epidural anesthesia with and without local heating. RESULTS AND
      COMMENTS: All patients had a sensory blockade covering at least T1-5. Cutaneous
      blood flow increased in all six patients after blockade (13.6 ml/min/100 g, range
      10.6-14.6 vs. 18.4 ml/min/100 g, range 13.9-24.5; P<0.05). Local heating did not
      further enhance blood flow. CONCLUSION: High TEA is associated with a uniform
      increase in thoracic cutaneous blood flow, and is suggestive of regional
      sympatholysis. Quantitative measurements of skin blood flow appear promising for
      documenting regional sympatholysis during TEA.

PMID- 12190810
TI  - Bilateral continuous paravertebral catheters for reduction mammoplasty.
AB  - Surgical procedures of the breast can result in significant postoperative pain.
      Paravertebral nerve blocks have been used successfully in the management of
      analgesia after breast surgery but are limited by a single injection. This report
      describes the use of bilateral paravertebral catheters to provide extended
      analgesia for reduction mammoplasty. A 48-year-old female underwent bilateral
      paravertebral catheter placement at thoracic level 3 and local anesthetic
      injections followed by general anesthesia for elective reduction mammoplasty. She
      reported no pain following the operation and required no supplemental opioids for
      pain management during her overnight recovery. This case demonstrates a method
      for extended bilateral thoracic analgesia. The technique may offer an alternative
      to traditional outpatient analgesics for reduction mammoplasty.

PMID- 12190811
TI  - Prolonged apnea following succinylcholine administration in undiagnosed acute
      organophosphate poisoning.
AB  - Organophosphates (OP) are irreversibly bound to cholinesterase, causing
      deactivation of acetylcholinesterase. As a result of inhibition of plasma
      cholinesterase, increased sensitivity to drugs hydrolyzed by this enzyme can
      occur, e.g. succinylcholine and mivacurium. A case of more prolonged
      succinylcholine-induced paralysis in a child with undiagnosed acute OP
      insecticide poisoning is presented. A 7-h period of apnea and paralysis after
      administration of succinylcholine was attributed to the decreased rate of
      succinylcholine metabolism resulting from inhibition of pseudocholinesterase by
      the insecticide. In seven previously reported cases of prolonged succinycholine
      apnea after OP poisoning, exposure to insecticide was in chronic or subacute form
      without any obvious symptoms, and the duration of apnea did not extend up to 4 h,
      whereas in our case with acute, severe poisoning, succinylcholine led to more
      prolonged muscle paralysis. In the anesthetic management of patients with acute
      OP poisoning, succinylcholine should be avoided.

PMID- 12190812
TI  - Post-dural puncture syndrome in an elderly patient with remote history of
      previous post-dural puncture syndrome.
AB  - History of previous post-dural puncture syndrome (PDPS) is a strong risk factor
      for another PDPS when spinal anesthesia is readministered to these patients. We
      herein report a case to show that this general rule may still apply even after
      the passage of 50 years.

PMID- 12190813
TI  - Risk of oral cancer associated with human papillomavirus infection, betel quid
      chewing, and cigarette smoking in Taiwan--an integrated molecular and
      epidemiological study of 58 cases.
AB  - BACKGROUND: The association between oral squamous cell carcinoma (OSCC) and human
      papillomavirus (HPV) 6, 11, 16 and 18 is uncertain. Past reports varied in the
      methodology and results. We conducted this study using in situ PCR in situ
      hybridization (ISH) assay which was considered as the most sensitive method for
      detection of viral DNA. We undertook an epidemiologic survey about the history of
      betel quid chewing and cigarette smoking, since these habits are common in
      Taiwan. METHODS: In situ PCR ISH was performed on the tumor specimens from 29
      patients with OSCC and the oral mucosal specimens from 29 patients without OSCC.
      Their betel quid chewing and cigarette smoking histories were also reviewed.
      RESULTS: HPV16, HPV18, betel quid chewing and cigarette smoking were
      statistically significant risk factors in univariate analysis. HPV6 and 11 were
      not. Multivariate analysis showed that HPV16 infection (adjusted Odds ratio =
      11.20) and betel quid chewing (adjusted Odds ratio = 17.06) remained to be
      independent factors for OSCC. CONCLUSIONS: Our results showed that HPV16 and
      betel quid chewing were two major risk factors for OSCC in Taiwan, indicating
      that they act through different mechanisms in the pathogenesis of OSCC.

PMID- 12190814
TI  - The increase in the frequency of MICA gene A6 allele in oral squamous cell
      carcinoma.
AB  - BACKGROUND: Oral squamous cell carcinoma (OSCC) was reported to be associated
      with immune function. The MICA (MHC class I chain-related gene A) is expressed by
      keratinocytes and other epithelial cells, and its encoded protein interacts with
      gamma/delta T cells localized in submucosa. The MICA also influences the heat
      shock protein function. We speculated that the alterations of MICA might
      influence the pathogenesis of OSCC through the aberration in presenting tumor
      antigens or heat shock protein. MICA gene has a triplet repeat (GCT) polymorphism
      in the transmembrane domain, resulting in five distinctive allelic patterns.
      METHODS: We analysed this MICA polymorphism in 67 OSCC patients and 351 randomly
      selected unrelated controls. By using the ABI Prism 377-18 DNA sequencer (Applied
      Biosystems, Foster City, CA, USA) to analyse the sample DNA PCR products. The
      number of micro-satellite repeats was estimated with Genescan 672 software
      (Applied Biosystems) with a standard size marker of GS-350 TAMRA (N,N,N,N
      tetramethyl-6-carbohydroxyl rhodamine; Applied Biosystems). RESULTS: The
      phenotype frequency of allele A6 of MICA in subjects with OSCC was significantly
      higher than that in controls (RR = 3.46, 95% CI = 1.73-6.94, P = 0.0002), as was
      the frequency of allele (RR = 2.64, 95% CI = 1.39-5.02, P = 0.002). CONCLUSION:
      The results suggest that allele A6 in MICA might confer the risk of OSCC.

PMID- 12190815
TI  - The relationship between MMPs and pH in whole saliva of radiated head and neck
      cancer patients.
AB  - BACKGROUND: Radiation therapy for head and neck tumour patients may lead to
      decreased salivary flow, oral mucosal lesions and increased caries experience.
      Salivary matrix metalloproteinases (MMPs) may participate in the pathogenesis of
      mucosal lesions and dentinal caries. The aims of this study were: (i) to assay
      the presence, molecular forms and proteolytic activity of MMP-8 (collagenase-2)
      and MMP-9 (gelatinase B) in the whole saliva of head and neck cancer patients
      having radiation therapy; (ii) to see whether salivary pH affects the activity of
      MMP-8 and MMP-9; and (iii) to find out the possible connection between MMP-8 and
      MMP-9 with the eruption of oral mucosal lesions during radiation therapy.
      METHODS: The whole saliva samples of 39 head and neck cancer patients having
      radiation therapy were collected before, during and after radiation therapy, and
      saliva flow rate, pH, buffer capacity, Streptococcus mutans, Lactobacillus and
      Candida albicans were measured. Any oral mucosal lesions were examined during
      each visit. The levels of MMP-8 were measured by immunofluorometric assay (IFMA)
      and the presence of different MMP-8 forms was analysed using Western
      immunoblotting. The presence and molecular forms of MMP-9 were analyzed by
      gelatin zymography. MMP-9 capture activity assay was used to determine the APMA
      activated MMP-9 activity (total) and the endogenously active MMP-9 (free
      activity). RESULTS: Salivary flow rate, buffer capacity and pH decreased, and the
      levels of Lactobacilli increased significantly, during the first half of the
      radiation therapy. The endogenously activated salivary MMP-9 correlated with low
      salivary pH (P = 0.013). No connection was found between the oral mucosal lesions
      and salivary MMP-8 or MMP-9. CONCLUSIONS: In this study, salivary MMP-8 or MMP-9
      did not correlate with the presence of radiation induced oral mucosal lesions,
      but the activation of MMP-9 may be dependent on pH.

PMID- 12190816
TI  - Interleukin-1 beta induces interleukin-6 mRNA expression and protein production
      in synovial cells from human temporomandibular joint.
AB  - BACKGROUND: Interleukin (IL)-1 beta and IL-6 were found to be elevated in fluid
      from the temporomandibular joint (TMJ), although the source of these cytokines
      was not elucidated. There is little known about the function and response of
      synovial cells in the TMJ. The purpose of this study was to prepare cultured
      human synovial cells (HTS cells) from the TMJ and to investigate IL-6 production
      in HTS cells incubated with IL-1 beta. METHODS: HTS cells were isolated from
      temporomandibular joint synovial tissue using an outgrowth method and then
      cultured in Ham's F12 medium containing 10% fetal bovine serum. The HTS cells
      were treated with or without IL-1 beta for 3, 6, 9 and 24 h. IL-6 and soluble IL
      6 receptor (sIL-6R) levels in cultured supernatant were measured by ELISA. IL-6
      mRNA expression was investigated using immunocytochemistry and RT-PCR. RESULTS:
      HTS cells were morphologically heterogeneous. IL-1 beta increased IL-6 production
      in HTS cells. In those treated with IL-1 beta, several cells were strongly
      stained in the cytoplasm around the nucleus, while several cells were weakly
      stained in this area. IL-1 beta also stimulated IL-6 mRNA expression. In
      contrast, sIL-6R could not be detected in cells treated with or without IL-1
      beta. CONCLUSIONS: IL-1 beta increased IL-6 production in synovial cells
      resulting from an increase in IL-6 mRNA expression. Enhanced production of IL-6,
      which is associated with bone resorption and inflammatory response, seems to be
      related to the progression of TMJ disorders.

PMID- 12190817
TI  - Will the Carers and Disabled Children Act 2000 make a difference to the lives of
      disabled children and their carers?

PMID- 12190818
TI  - Participation in childhood.

PMID- 12190819
TI  - Sure Start: reflections from Down Under.

PMID- 12190820
TI  - The recruitment and training crisis in community paediatrics: what do registrars
      think?
AB  - OBJECTIVE: There is currently a crisis in the recruitment of trainees into
      community paediatrics. Focus groups were conducted to explore the views of
      paediatric specialist registrars about this crisis. DESIGN: A total of 18
      registrars participated in two focus groups. Data were analysed qualitatively by
      content analysis. RESULTS: The overriding theme was the poor status and image of
      community compared with acute paediatrics. This existed at five levels, which
      could be arranged from a 'macro' structural level down to a 'micro' individual
      level. These were: the hospital/community divide, issues related to training,
      practical experience, the influence of role models, and personal factors.
      CONCLUSIONS: We identified several specific implications for community paediatric
      training. However, the deep divide between acute and community paediatrics, as
      perceived by registrars, is unlikely to change unless training programmes are
      designed to produce paediatricians suited to the needs of future child health
      services rather than existing models of acute and community paediatricians.

PMID- 12190821
TI  - In my opinion: reflections of a journal reviewer.

PMID- 12190830
TI  - Longitudinal research on the menopause-methodological challenges.

PMID- 12190831
TI  - Statistical techniques for the analysis of change in longitudinal studies of the
      menopause.
AB  - OBJECTIVE: Critical review of statistical techniques used to analyze data from
      longitudinal studies. METHOD: Literature search and classification of statistical
      methods and their utilization evaluated against known underlying assumptions.
      RESULTS: One hundred and twenty-three papers found: 1. cross-sectional reduction
      of data (56%); 2. multifactorial techniques (26%); 3. repeated measurement
      analysis of variance (14%); 4. other (time series and structural equation
      modelling) (4%). CONCLUSIONS: Cross-sectional reduction violates underlying
      statistical assumptions. A simple and powerful technique is to mean values prior
      to and following an event such as the final menstrual period. To allow for the
      influence of multiple factors, linear regression is preferred to logistic
      regression where continuous data are available. For more information about
      evolution in time, more complex techniques are needed. A suitable technique is
      repeated measurement multivariate analysis of variance using a number of
      contrasts to estimate various effects. Split plot or randomized block designs
      cannot be recommended as they violate compound symmetry assumptions. For series
      involving more than 100 observations for each subject, time series and spectral
      analysis techniques should be considered. Structural equation modelling is
      recommended for examination in detail of a range of factors that may influence
      the studied end-point, the presence of feedback and of latent or non-measurable
      variables.

PMID- 12190832
TI  - Menstrual diary data and menopausal transition: methodologic issues.
AB  - OBJECTIVES: To identify problems arising in the analysis of menstrual diary data
      in a longitudinal study of the menopausal transition, and to propose solutions.
      SUBJECTS AND METHODS: Menstrual diary information provided by 372 women over a
      period 7 years is the basis of the study. This paper considers the processes and
      decisions associated with transforming this information into a form suitable for
      answering research questions. RESULTS: We decided to use 'cycle' as the unit of
      analysis and to regard spotting-only episodes as nonmenstrual bleeding.
      Difficulties in distinguishing between long cycles and gaps because of recording
      lapses are shown to be related to both the design of the menstrual diary cards
      and the procedures used by fieldworkers. A new design that should minimize such
      difficulties is presented. Procedural changes are also proposed. CONCLUSIONS: It
      is important to minimize uncertainty about the meaning of gaps in menstrual diary
      data, especially in studies of the menopausal transition. Methodologic
      improvements that can help to achieve this aim include design of diary cards and
      fieldwork procedures to reduce uncertainty. The design of data entry interfaces
      to facilitate the checking of raw data and the use of graphs as a diagnostic tool
      are other important steps.

PMID- 12190833
TI  - Physical activity: measurement in mid-life women.
AB  - OBJECTIVES: To review methods of assessing physical activity, and to compare two
      different questionnaires that were administered in the Melbourne Women's Midlife
      Health Project (MWMHP). METHODS: Cross-sectional and subsequent longitudinal
      population-based study of Australian-born women who were aged 45-55 at baseline.
      Self-administered modified form of the Minnesota Leisure-Time Physical Activity
      questionnaire and interviewer-administered short physical activity question.
      RESULTS: Two hundred and ninety-two women completed the Minnesota Leisure-Time
      Physical Activity questionnaire at both cross-sectional and 3rd year of follow-up
      (L3) and there was no difference in the total mean time spent exercising at both
      phases [5.9 (SD, 5.7) and 5.8 (SD, 5.0) hours per week, respectively]. The
      responses to the two questionnaires were significantly associated (beta = -0.89,
      SE 0.17, p < 0.0005). Using the Minnesota Leisure-Time Physical Activity
      questionnaire between the cross-sectional and L3 phases, 10% of the women
      increased the time they spent exercising by 5 h per week and 10% decreased it by
      the same amount. Using the short exercise question, 12% of women decreased their
      participation by two or more sessions per week and 14% increased their
      participation by this amount between the cross-sectional and L3 phases.
      CONCLUSION: In this cohort of mid-life women the short exercise question was
      comparable in terms of measuring participation and change in physical activity
      with the more complex Minnesota Leisure-Time Physical Activity questionnaire.

PMID- 12190834
TI  - Menopause, energy expenditure, and body composition.
AB  - OBJECTIVES: The effects of menopause transition on metabolic and cardiovascular
      disease risk in women are unclear. It is unknown whether estrogen deficiency,
      aging, or a combination of both factors are independent contributors to a
      worsening health profile in women. We considered the effects of menopause
      transition and hormone replacement therapy on body composition, regional body
      fat, energy expenditure, and insulin sensitivity. METHODS: A brief review of
      current literature that has considered the role of menopause transition and
      hormone replacement therapy on body composition, energy expenditure, and insulin
      sensitivity with an emphasis on longitudinal investigations. RESULTS: Preliminary
      evidence suggests that natural menopause is associated with reduced energy
      expenditure during rest and physical activity, an accelerated loss of fat-free
      mass, and increased central adiposity and fasting insulin levels. Hormone
      replacement therapy has been shown to attenuate these changes. Longitudinal and
      longer intervention studies are needed to confirm these initial findings.
      CONCLUSIONS: Menopause transition may represent a risky period in a woman's life,
      'triggering' adverse metabolic and cardiovascular processes that predispose women
      to a greater incidence of obesity-related comorbidities. Dietary, exercise, and
      hormonal interventions specifically targeted at premenopausal women may help
      mitigate the worsening cardiovascular and metabolic risk profile associated with
      menopause.

PMID- 12190835
TI  - Reproductive hormones: ageing and the perimenopause.
AB  - This review explores the pituitary-ovarian hormones involved with ageing and the
      onset of menopause. The serum patterns of pituitary-ovarian hormones throughout
      the menstrual cycle alter as menopause approaches. The increase in follicular
      phase FSH prior to menopause is attributed to an early decline in the ovarian
      hormone, inhibin B, which negatively regulates follicle-stimulating hormone (FSH)
      secretion. Serum inhibin B is believed to reflect the age-related decrease in
      ovarian follicle reserve, which is the primary source of serum inhibin B. The
      later rise in serum luteinizing hormone (LH) during the menopause transition is
      due to a cessation of ovarian follicle development. Hormonal patterns during the
      luteal phase of the menstrual cycle also show changes with age but these changes
      are poorly understood.

PMID- 12190836
TI  - Longitudinal study of menopause and sexuality.
AB  - Longitudinal study of the menopause and sexuality involves many problems that may
      account for the small number of such studies. In seeking subjects, the mention of
      sexuality is best delayed until the initial interview when subjects can be
      informed of the strict confidentiality of the data and be assured that having a
      sex partner is not a requirement for participation. It is best if subjects are
      required to be early perimenopausal with regular menstrual cycles but with a
      change in cycle length and/or flow. Important demographic variables of interest
      are ethnicity, education, socioeconomic status, health, and partner status.
      Subjects who have had reproductive surgery or use medications likely to affect
      sexuality are properly excluded from study or studied as a separate group.
      Measures include daily calendars for prospective recording of menstruation and
      sexual behavior as well as repeated questionnaires assessing menopausal symptoms
      and sexuality; questionnaires should be designed to obtain data concerning sexual
      interest, sexual attractiveness, and sexual response. It is desirable to measure
      sex hormone levels at regular intervals if possible. Technological advances have
      added new and better methods of data collection and have increased the chance of
      getting accurate prospective data. Nonetheless a good relationship with the
      investigator is important in obtaining subject co-operation and avoiding
      attrition. Future studies need to attempt to collect data from sex partners of
      subjects as well as explore the effects of different sex hormone products and
      regimens on sexual attractiveness, sexual interest, and sexual response.

PMID- 12190837
TI  - Patterns of depressed mood across the menopausal transition: approaches to
      studying patterns in longitudinal data.
AB  - To date many researchers have focused on depression as a discrete episode,
      attempting to relate its occurrence to a transition in menopausal stage or other
      factors that might account for its occurrence. Characterizing change over time
      requires consideration of pattern or trajectory, not merely discrete events. The
      purposes of this paper are to: 1) to explore methods for intraindividual and
      interindividual (group) analysis of patterns of depressed mood among midlife
      women 2) to identify challenges for analytic strategies for understanding
      depressed mood as it is experienced by midlife women, with special concern for
      its relationship to the menopausal transition. Data from the Seattle Midlife
      Women's Health Study were used to illustrate approaches to intraindividual and
      interindividual analysis of patterns of depressed mood. For most women,
      menopausal transition was not a time when there was a new episode of depression.
      Instead, a minority of women showed evidence of becoming depressed once the
      transition had begun. The most prevalent pattern was that of non-depressed mood
      across the years of the menopausal transition. Association of several factors
      with a pattern of depressed mood included life stressors, perceived poor health,
      and vasomotor symptoms.

PMID- 12190838
TI  - Development and clinical experience with the new evidence-based tocolytic
      atosiban.
AB  - The incidence of preterm birth has remained unchanged for the last few decades.
      This is due, in part, to the complex etiology of preterm labor, and the limited
      ability of tocolytic agents to prolong pregnancy as a result of limited efficacy
      and poor safety profiles. The recent introduction of the oxytocin antagonist,
      atosiban, represents a new generation of uterine-specific tocolytics, which are
      associated with more favorable safety profiles. This paper discusses the
      rationale behind the development of the oxytocin antagonists and provides a
      review of the phase II and III trials that have investigated atosiban. Also
      included is a retrospective analysis of 83 women assessed in the Vienna Medical
      School, providing an insight into the benefits associated with atosiban in the
      everyday clinical setting. The introduction of a safer tocolytic agent offers the
      potential to change the current approach to the management of preterm labor. This
      includes a prolonged period of treatment at earlier or later gestational ages and
      possibly an extended use to women with contraindications who would normally have
      been excluded from treatment, e.g. preterm premature rupture of the membranes.

PMID- 12190839
TI  - Could an infectious trigger explain the differential maternal response to the
      shared placental pathology of preeclampsia and normotensive intrauterine growth
      restriction?
AB  - Preeclampsia/eclampsia remains an important cause of maternal and perinatal
      morbidity and mortality. Its origins lie in a mismatch between fetoplacental
      demands and the ability of the uteroplacental arteries to supply those demands, a
      situation that also arises in normotensive intrauterine growth restriction (the
      fetal syndrome of preeclampsia in isolation). Why is there this differential
      response to the same underlying pathology? This review summarises the evidence
      surrounding a potential trigger for the differential response, namely infection.
      This builds on the inflammatory model of preeclampsia for which there is
      increasing support. The evidence for an infectious trigger is principally
      indirect, linking the similarities between acute atherosis in preeclampsia and
      atherosclerosis, the increased likelihood of developing cardiovascular disease
      later in life following a preeclampsia pregnancy, and the association between
      chronic infection and atherogenesis. Also reviewed is the human and animal model
      evidence for an infectious trigger for preeclampsia. Perhaps preeclampsia truly
      is the 'toxemia' of pregnancy.

PMID- 12190840
TI  - Hormone replacement therapy with tibolone: effects on sexual functioning in
      postmenopausal women.
AB  - OBJECTIVE: Because hormonal changes in postmenopausal women may be accompanied by
      sexual problems and a worsening of various aspects of libido, the aim of this
      study was to assess the effect of tibolone (Liviel(R)) on sexual life. METHODS:
      Postmenopausal first-time users of hormone replacement therapy (HRT) were
      included in this open, multicenter study. Patients were treated with tibolone 2.5
      mg daily for at least 4 months. Both at baseline and after 4 months of treatment,
      patients were asked to complete two different questionnaires rating the women's
      subjective assessment of their sexual problems or desires. RESULTS: One hundred
      and eighty-four women were enrolled to receive HRT with tibolone. Overall, a
      significant increase in women's satisfaction with their sexual lives and a
      significant improvement in different aspects of libido was found. CONCLUSION:
      Tibolone has beneficial effects on several aspects of sexual life in
      postmenopausal women. These effects may be due to both an increase in genital
      blood flow and the central estrogenic/androgenic activity.

PMID- 12190841
TI  - Intermittent progestin administration as part of hormone replacement therapy:
      long-term comparison between estradiol 1 mg combined with intermittent
      norgestimate and estradiol 2 mg combined with constant norethisterone acetate.
AB  - BACKGROUND: To decrease exposure to progestin during hormone replacement therapy
      (HRT), a novel oral regimen consisting of constant 17beta-estradiol (E2) daily
      plus intermittent norgestimate (NGM) has been developed. METHODS: A multicenter
      study compared the safety and efficacy of E2 1 mg daily plus intermittent NGM 90
      micro g (3 days off, 3 days on) (n = 150) vs. a continuous oral dose of E2 2 mg
      plus norethisterone acetate (NETA) 1 mg (n = 172) daily, for a period of 2 years.
      Endometrial biopsies were performed at 1 and 2 years. Subjects recorded the
      occurrence of vasomotor symptoms, uterine bleeding, and adverse events on diary
      cards. RESULTS: At 2 years' follow-up, no subject had developed endometrial
      hyperplasia or cancer. Endometrial atrophy was seen in 75% of subjects using the
      intermittent NGM regimen and in 78% of women using the constant NETA regimen.
      Both groups maintained a 96% reduction in vasomotor symptoms up to 2 years. The
      rates of bleeding and/or spotting showed no difference between the groups, and at
      2 years' follow-up, 73% of women in the intermittent NGM group and 83% of
      subjects in the constant NETA group were amenorrheic. There was a lower incidence
      of progestin-associated side-effects, such as abdominal discomfort, edema,
      painful bleeding episodes, and breast symptoms, with the intermittent progestin
      regimen vs. the constant progestin regimen. Intermittent NGM use was associated
      with an elevation in HDL- and HDL2-cholesterol, whereas constant NETA reduced
      these lipoproteins. CONCLUSIONS: The intermittent administration of a progestin,
      such as NGM, provides a new, well-tolerated regimen to achieve endometrial
      safety, an adequate rate of amenorrhea, and effective reduction of vasomotor
      symptoms in postmenopausal women.

PMID- 12190842
TI  - Symptom-free women at increased risk of ectopic pregnancy: should we screen?
AB  - BACKGROUND: Transvaginal sonography, serum human chorionic gonadotrophin (hCG)
      measurement, and serum progesterone measurement provide the possibility to screen
      symptom-free women at increased risk of ectopic pregnancy. The objective of the
      present study was to evaluate the cost-effectiveness of screening for ectopic
      pregnancy, by addressing the expected benefits and costs of screening for ectopic
      pregnancy. METHODS: Screening programs incorporating transvaginal sonography,
      serum hCG measurement, and serum progesterone measurement were compared with a
      'watchful waiting' strategy. Data were extracted from the literature. The
      strategies were compared on the expected number of prevented tubal ruptures, the
      expected number of false-positive diagnoses, and expected costs. RESULTS: The
      cost-effectiveness of screening appeared to be strongly dependent on the
      prevalence of ectopic pregnancy. At a prevalence of ectopic pregnancy of 6%, a
      screening program with transvaginal sonography and serum hCG measurement would
      reduce the number of patients with ruptured ectopic pregnancy from 2.1 to 0.61
      per 100 screened women. Screening was expected to cost approximately Euro 933 per
      prevented tubal rupture, whereas the number of expected false-positive diagnoses
      was 0.64 per prevented tubal rupture. CONCLUSION: We conclude that screening for
      ectopic pregnancy reduces the number of patients with tubal rupture, but only at
      the expense of a large false-positive rate. Although sonography in symptom-free
      women at risk of ectopic pregnancy might be justified for psychological reasons,
      the medical and economic benefits of such a policy seem to be limited.

PMID- 12190843
TI  - Fundal hiatus discovered in a presumably unscarred uterus at emergency cesarean:
      an old perforation or rupture?

PMID- 12190844
TI  - Vaginal infection with methicillin-resistant Staphylococcus aureus after
      laparoscopic supracervical hysterectomy.

PMID- 12190845
TI  - Primary osteosarcoma of the uterus with immunohistochemical study.

PMID- 12190846
TI  - Hysteroscopy in 2001: a comprehensive review.

PMID- 12190852
TI  - Serological evidence of alpha herpesvirus infection in sooty mangabeys.
AB  - Contact between sooty mangabeys (SMs) and a pigtailed macaque prompted the
      serological screening of SMs for evidence of infection with B virus. Serological
      tests detected SM antibodies that reacted with B virus polypeptides. Additional
      testing was performed with sera from SMs with no previous contact with macaques.
      Results from these tests indicated that 56% (33/59) of the SMs had antibodies
      that reacted with B virus and SA8. SM antibodies also reacted with herpesvirus
      papio 2 and to a lesser extent with human alpha herpesviruses (HSV-1 and HSV-2).
      There was an age-related increase in the presence of these antibodies in SMs that
      was consistent with the serological pattern of reactivity observed in other
      nonhuman primate species infected with alpha herpesviruses. These data suggest
      that SMs may be a host for a herpesvirus that is antigenically similar to those
      viruses present in other Old World nonhuman primates.

PMID- 12190851
TI  - Postnatal pre- and postexposure passive immunization strategies: protection of
      neonatal macaques against oral simian-human immunodeficiency virus challenge.
AB  - Simian-human immunodeficiency viruses (SHIV) allow the evaluation of antiviral
      strategies that target the envelope glycoproteins of the human immunodeficiency
      virus 1 (HIV-1) in macaques. We previously protected neonates from oral challenge
      with cell-free SHIV-vpu+ by passive immunization with synergistic human
      neutralizing monoclonal antibodies (mAbs) (Baba et al., Nat Med 6:200-206, 2000).
      mAbs were administered prenatally to pregnant dams and postnatally to the
      neonates. Here, we used solely postnatal or postexposure mAb treatment, thus
      significantly reducing the amount of mAbs necessary. All neonatal monkeys were
      also protected with these abbreviated mAb regimens. Our results are directly
      relevant for humans because we used mAbs that target HIV-1 envelope
      glycoproteins. Thus, the large-scale use of passive immunization with
      neutralizing mAbs may be feasible in human neonates. The mAbs, being natural
      human proteins, can be expected to have low toxicity. Passive immunization has
      promise to prevent intrapartum as well as milk-borne virus transmission from HIV
      1-infected women to their infants.

PMID- 12190853
TI  - Yersinia pseudotuberculosis infection in breeding monkeys: detection and analysis
      of strain diversity by PCR.
AB  - In the last three decades, several monkeys reared in outdoor/indoor-outdoor
      breeding colonies and cages of the Primate Research Institute, Kyoto University,
      died of yersiniosis caused by Yersinia pseudotuberculosis, necessitating
      introduction of a method to detect the bacteria rapidly and thus allow preventive
      measures to be undertaken. A rapid nested polymerase chain reaction (PCR) method
      for identification of Y. pseudotuberculosis in fecal samples and a random
      amplified polymorphic DNA (RAPD)-PCR approach for distinguishing between
      bacterial strains were therefore developed. Yersinia pseudotuberculosis isolates
      from monkey specimens were found to be classifiable into several types. To
      determine the source of infection, hundreds of fecal samples of wild rats,
      pigeons, and sparrows were collected from around the breeding colonies and cages,
      and subjected to PCR analyses. Yersinia pseudotuberculosis was detected in 1.7%
      of the fecal samples of wild rats. The DNA fingerprints of the bacteria revealed
      by RAPD-PCR were the same as that of one strain isolated from macaques,
      suggesting the wild rat to be a possible source of infection.

PMID- 12190854
TI  - ABO blood groups in the primate species of Cebidae from the Amazon region.
AB  - The ABO blood groups were determined in blood and saliva collected from 40 Aotus
      infulatus, 74 Saimiri sciureus, and 96 Cebus apella from the Amazonian region
      along the Tocantins river. Saliva samples were tested for human ABH antigens by a
      standard hemagglutination inhibition test. Aotus infulatus showed monomorphism,
      exhibiting only the B blood group. Saimiri sciureus exhibited the A (67) and AB
      (7) phenotypes. All four phenotypes have been found in C. apella: O (8), A (52),
      B (19) and AB (17). The observed distribution was as expected assuming Hardy
      Weinberg equilibrium. The titers of ABH substances varied among the species and
      phenotypes. The B-like agglutinogen, common to all New World monkey species
      tested, was detected in the red blood cells. Sera were used to detect naturally
      occurring antibodies and the results showed discrepancies between serum and
      saliva phenotypes in all species studied.

PMID- 12190855
TI  - Spontaneous terminal ileitis resembling Crohn disease in captive tamarins.
AB  - Five tamarins (four Saguinus mystax and one S. labiatus) died with wasting
      syndrome characterized by chronic diarrhea at the Center for Reproduction and
      Conservation of Non-Human Primates in Iquitos, Peru. At necropsy, the terminal
      ileum of all affected tamarins was found to be markedly thickened.
      Histologically, the terminal ileal mucosa was completely ulcerated, and effaced
      by debris and mononuclear inflammatory cells. The submucosa and serosa were
      thickened by fibroplasia, mononuclear cell infiltrates and variable edema. No
      infectious agent was observed. The lesions were similar to those described
      previously for Crohn disease. This is to our knowledge the first report of
      terminal ileitis resembling Crohn disease in non-human primates.

PMID- 12190856
TI  - Neonatal behavioral scoring of common marmosets (Callithrix jacchus): relation to
      physical condition and survival.
AB  - A seven-task behavioral test was performed on 86 common marmoset (Callithrix
      jacchus) infants, 24-36 h following birth. This report describes the test outcome
      and its relation to physical condition and survival of the infants. The
      percentage of infants receiving a perfect score on a given task ranged from 30.6
      (rooting) to 70.6% (grasping). Heavier infants were more likely to have perfect
      scores for crawling (F=4.20, P=0.044) and infants with a longer knee-heel length
      tended to be more likely to have a perfect grasping score (F=3.63, P=0.06). While
      the modal score was a perfect score for most individual tasks, the modal number
      of total perfect scores that a given infant received was 3-4 and only 4.7% of
      infants received perfect scores on all seven tasks. These results suggest that
      this group of behavioral tasks will produce a variable response within a
      population of neonates. While no individual behavioral score predicted survival
      during week 1, the number of perfect scores across all tasks was predictive of
      survival outcome; infants with a higher total number of perfect scores were more
      likely to survive (F=6.02, P=0.018). When all combinations of tests were
      compared, the best predictor of survival was outcome on four of the seven tests,
      all related to motor skills (F=7.46, P=0.009).

PMID- 12190857
TI  - In this issue: casting a net.

PMID- 12190858
TI  - Essential roles for dendritic cells in the pathogenesis and potential treatment
      of HIV disease.
AB  - During sexual transmission of HIV, virus crosses mucosal epithelium and
      eventually reaches lymphoid tissue where it establishes a permanent infection.
      Evidence has accumulated that infection of Langerhans cells, which are resident
      dendritic cells in pluristratified epithelia, plays a crucial role in the early
      events of HIV transmission. HIV infection of Langerhans cells is regulated by
      surface expression of CD4 and CCR5. Thus, topical microbicides that interfere
      with HIV infection of Langerhans cells represent an attractive strategy for
      blocking sexual transmission of virus. Capture and uptake of HIV virions is
      another major pathway by which HIV interacts with dendritic cells. By contrast,
      this process is mediated by a newly described C-type lectin, DC-SIGN. It is well
      established that HIV-exposed dendritic cells transmit virus efficiently to
      cocultured T cells. Indeed, dendritic cell-T cell interaction, critical in the
      generation of immune responses, is a rich microenvironment for HIV replication
      both in vitro and in vivo. Dendritic cells that have captured virus via DC-SIGN,
      and not HIV-infected dendritic cells, probably facilitate most infection of T
      cells in chronically infected individuals. Therefore, blocking DC-SIGN-mediated
      capture of HIV represents a potential therapeutic antiviral strategy for HIV
      disease. Lastly, dendritic cells have been targeted both ex vivo and in vivo to
      initiate and enhance HIV-specific immunity. Although these approaches are
      promising for both therapeutic and prophylactic vaccines, much additional work is
      needed in order to optimize dendritic-cell-based immunization strategies.

PMID- 12190859
TI  - IL-2-IgG2b fusion protein suppresses murine contact hypersensitivity in vivo.
AB  - Interleukin-15 shares several functional properties with interleukin-2, and
      signals through the beta and gamma chain of the interleukin-2 receptor as well as
      through its own high affinity alpha chain. In agreement with the concept that
      interleukin-2 plays a key role in type IV immune responses, we have recently
      shown that an IL-2-IgG2b fusion protein potently suppresses Th1-type delayed type
      hypersensitivity reaction and Th2-type allergic sensitization in mice. We have
      now compared the in vivo effects of IL-2-IgG2b fusion protein with those of IL-15
      IgG2b fusion protein in a murine model of Th1-type contact hypersensitivity
      reaction. Daily systemic injections of IL-2-IgG2b fusion protein during the
      sensitization phase or application of IL-2-IgG2b fusion protein just 2 h before
      and 10 h after antigen challenge significantly inhibited the contact
      hypersensitivity ear swelling response, and this without any overt signs of
      associated toxicity. Even local injection of IL-2-IgG2b fusion protein into the
      earlobe around the time of antigen challenge inhibited the ear swelling reaction
      significantly. In contrast, neither systemic nor local injection of the IL-15
      IgG2b fusion protein modulated the contact hypersensitivity reaction
      significantly. IL-2-IgG2b but not IL-15-IgG2b fusion protein reduced migration of
      antigen-presenting cells from the skin to local lymph nodes, inhibited the
      expression of CD80 and CD86, and induced a significant higher number of CD4+CD25+
      T cells. Therefore, the IL-2-IgGb fusion protein offers a powerful tool for
      suppressing and/or preventing T-cell-mediated hypersensitivity reaction in vivo.

PMID- 12190860
TI  - T cell receptor Beta chain gene usage in endemic pemphigus foliaceus (fogo
      selvagem).
AB  - The trimolecular complex comprised of the major histocompatibility complex,
      peptide antigen, and the T cell receptor is a requisite for T cell activation in
      normal and autoimmune responses. T cell receptor analysis is critical to further
      our understanding regarding mechanisms of T cell epitope selection and autoimmune
      initiation and progression and may help to identify targets for immunotherapy.
      Pemphigus foliaceus is an autoimmune blistering skin disease characterized by
      intraepidermal blisters and circulating autoantibodies directed against
      desmoglein 1, a 160 kDa transmembrane desmosomal molecule expressed in
      keratinocytes. As tissue damage is mediated by anti-desmoglein 1 antibodies, an
      initial T cell response is a likely requirement for autoantibody generation in
      this disease. To elucidate the role of pathogenic T cells in autoimmunity
      further, we have directly characterized the T cell receptor of T cells derived
      from pemphigus foliaceus patients. Complementary DNA was isolated from 17
      desmoglein 1 specific T cell clones generated from pemphigus foliaceus patients
      by clonal expansion in vitro. To analyze the T cell repertoire, a panel of
      primers, collectively specific for the known human T cell receptor beta variable
      region (TCRBV) families were paired with a constant region primer to polymerase
      chain reaction to amplify one distinct T cell receptor beta variable region
      allele for each T cell clone studied. Polymerase chain reaction products were
      sequenced to determine exact beta chain gene usage. In the 17 clones tested, 10
      distinct T cell receptor beta variable region usages and nine T cell receptor
      beta joining gene segment usages were identified. Furthermore, T cell receptor
      beta variable region and beta joining usage did not appear to be random, but
      oligoclonal in nature, with some preference shown for T cell receptor beta
      variable region 5S1 and T cell receptor BJ2S5.

PMID- 12190861
TI  - Psoriasis is mediated by a cutaneous defect triggered by activated immunocytes:
      induction of psoriasis by cells with natural killer receptors.
AB  - This study was performed to ask whether psoriasis is a unique pathologic response
      of epidermis of psoriatic patients, or cells with natural killer receptors can
      induce psoriatic changes in skin from nonpsoriatic donors. Human nonlesional skin
      from five psoriatics, as well as from seven nonpsoriatics was grafted on to beige
      SCID mice. Lymphocyte lines with natural killer activity, and mixed natural
      killer, natural killer T cell phenotype, were generated by culture of peripheral
      blood mononuclear cells from both psoriatic, and normal donors, in 100 U
      interleukin-2 per ml for 14 d. Natural killer cells were injected into the human
      skin grafts, and the grafts were harvested after 4 wk. Injection of natural
      killer cells from psoriatic donors into autologous nonlesional psoriatic skin
      resulted in classic psoriasis histology with a significant increase in epidermal
      thickness, and proliferation, as well as expression of epidermal human leukocyte
      antigen DR, intercellular adhesion molecule-1, CD1d, and K-16. Superantigen
      stimulation was not necessary. In contrast, injection of natural killer cells
      from normal donors into autologous normal skin did not induce the histology of
      psoriasis, but that of psoriasiform dermatitis. This is a nonspecific reaction
      pattern. These grafts also exhibited a significant increase in epidermal
      thickness, and proliferation. Differences from psoriasis included mild epidermal
      edema (spongiosis), hypergranulosis, irregular elongation of rete ridges, and
      lack of thinning of the suprapapillary plate. Injection of allogeneic natural
      killer cells into grafts also resulted in psoriasiform dermatitis, regardless of
      the source of natural killer cells, or skin. Psoriasis induction by cells with
      natural killer receptors appears to be dependent upon the source of skin. This
      suggests that psoriasis results from a cutaneous defect that is triggered by an
      autoimmune activation.

PMID- 12190862
TI  - Gene array profiling and immunomodulation studies define a cell-mediated immune
      response underlying the pathogenesis of alopecia areata in a mouse model and
      humans.
AB  - Alopecia areata is a suspected autoimmune hair loss disease. In a rodent model,
      alopecia areata can be induced in normal haired C3H/HeJ mice by transfer of skin
      grafts from mice with spontaneous alopecia areata. At weeks 2, 4, 6, and 10 after
      surgery, grafted mice were euthanized, skin collected and processed for
      histology, and RNA extracted. Age-matched sham-grafted mice, and mice with and
      without spontaneous alopecia areata, were similarly processed. For comparison,
      skin biopsies from alopecia areata and androgenetic alopecia affected humans were
      also collected. Skin mRNA processed to cDNA was analyzed using Affymetrix mouse
      11K and human 6800 gene chip(R) array technology. Microarray results indicated 42
      known genes upregulated or downregulated during onset of mouse alopecia areata
      consistent with an inflammatory cell-mediated disease pathogenesis involving
      antigen presentation, costimulation, and a T helper 1 lymphocyte response. In
      contrast, 114 genes, many regulating immunoglobulin response, were altered late
      in disease development. In alopecia areata affected humans, 95 genes were
      significantly modulated. As confirmation of microarray analysis results, lymph
      node and spleen cells from alopecia areata affected mice injected into normal
      haired littermates transferred the alopecia areata phenotype. Alopecia areata
      onset could be inhibited in skin-grafted mice by modulation with B7.1- and B7.2
      specific monoclonal antibodies. In addition, depletion of CD4+ CD8+ expressing
      cells in chronic alopecia areata affected mice using monoclonal antibodies
      permitted hair regrowth. The results consistently demonstrated the importance of
      an immune cell-mediated disease mechanism in alopecia areata pathogenesis and
      suggested targeting antigen-presenting cells and reactive lymphocytes may be
      effective in alopecia areata treatment.

PMID- 12190863
TI  - Interferon-gamma, a strong suppressor of cell proliferation, induces upregulation
      of keratin K6, one of the inflammatory- and proliferation-associated keratins.
AB  - Keratin K6 is known as an inflammatory and hyperproliferative keratin, and is
      induced by an inflammatory and hyperproliferative agent. In this study, we
      demonstrated that interferon-gamma, an antiproliferative agent, also induces
      keratin K6. We used normal human ex vivo skin, normal human cultured
      keratinocytes, HaCaT keratinocytes, and DJM cells to examine the induction of K6
      by interferon-gamma, by immunohistochemical staining, Western blot analysis,
      promoter chloramphenicol acetyl transferase assay, and reverse transcriptase
      polymerase chain reaction of mRNA. We succeeded in demonstrating the induction of
      keratin K6 by interferon-gamma in ex vivo human skin and HaCaT keratinocytes at
      the protein and message level, and in cultured normal human keratinocytes at the
      promoter level. The inhibition of the signal transducing activator of
      transcription 1 pathway by a dominant-negative transfer gene caused the
      inhibition of K6 induction by interferon-gamma, and the blocking of nuclear
      factor kappaB using antisense oligonucleotides also inhibited the K6 induction.
      We also blocked the released interleukin-1alpha from keratinocytes after
      stimulation with interferon-gamma by neutralizing antibodies, which showed a
      decrease in the K6 induction. Our results suggest that a small amount of
      interleukin-1alpha, which cannot induce K6 by itself, is secreted upon
      stimulation by interferon-gamma, and that the induction of K6 occurs through the
      synergistic effect of the interferon-gamma/signal transducing activator of
      transcription 1 and interleukin-1alpha/nuclear factor kappaB pathways. This is
      the first report to describe K6 induction in epidermal keratinocytes by
      interferon-gamma and indicate a probable signal transduction pathway, and
      demonstrates that K6 is a possible partner of K17 in the inflammatory process.

PMID- 12190864
TI  - A long-term coculture model for the study of mast cell-keratinocyte interactions.
AB  - Physiologic and pathologic events associated with cutaneous differentiation and
      repair are the result of a concerted action of various types of resident tissue
      cells. In vitro models simulating this complex in vivo situation are therefore
      needed to clarify the specific contribution and relevant interaction of, for
      example, dermal mast cells with other major cutaneous cells. The aim of this
      study was to establish a long-term coculture model that includes dermal mast
      cells, dermal fibroblasts, and keratinocytes in a human skin equivalent
      organotypic setting. Normal dermal mast cells and fibroblasts (1:4) were enclosed
      in collagen gel and normal keratinocytes were grown on top with exposure to the
      air interface. Under these conditions, mast cell integrity and functionality was
      preserved even after 4 wk of culture, as shown by electron microscopy and
      immunohistochemistry using antibodies against the mast-cell-specific granule
      enzyme tryptase and the receptors for stem cell factor and IgE. Mast cells also
      released histamine on stimulation with anti-IgE, and on ultrastructure were found
      to degranulate, with decrease of granule matrix density and formation of cell
      cell contacts with fibroblasts. After 2 wk of culture, keratinocytes had formed
      an epidermis-like multilayer and were able to proliferate and differentiate, as
      shown by bromodeoxyuridine incorporation of basal cells and immunohistochemical
      staining for transglutaminase and cytokeratins 1 and 10. The model presented here
      thus provides a potentially relevant tool to further clarify the interaction of
      dermal mast cells with major other skin cells and their contribution to cutaneous
      physiology, repair processes, and pathology.

PMID- 12190865
TI  - Human epidermal glucosylceramides are major precursors of stratum corneum
      ceramides.
AB  - Ceramides are the major component of the stratum corneum, accounting for 30%-40%
      of stratum corneum lipids by weight, and are composed of at least seven molecular
      groups (designated ceramides 1-7). Stratum corneum ceramides, together with
      cholesterol and fatty acids, form extracellular lamellae that are responsible for
      the epidermal permeability barrier. Previous studies indicated that beta
      glucocerebrosidase- and sphingomyelinase-dependent ceramide production from
      glucosylceramides and sphingomyelins, respectively, is important for epidermal
      permeability barrier homeostasis. A recent study indicated that sphingomyelins
      are precursors of two stratum corneum ceramide molecular groups (ceramides 2 and
      5). In this study, we have examined the role of glucosylceramides in the
      generation of each of the seven stratum corneum ceramide molecular groups. First,
      the structures of various glucosylceramide species in human epidermis were
      determined by gas chromatography-mass spectrometry, fast atom bombardment-mass
      spectrometry, and nuclear magnetic resonance. The results indicate that total
      epidermal glucosylceramides are composed of six distinct molecular groups,
      glucosylceramides 1-6. Glucosylceramide 1 contains sphingenine and nonhydroxy
      fatty acids, glucosylceramide 2, phytosphingosine and nonhydroxy fatty acids,
      glucosylceramide 3, phytosphingosine with one double bond and nonhydroxy fatty
      acids, glucosylceramide 4, sphingenine and alpha-hydroxy fatty acids,
      glucosylceramide 5, phytosphingosine and alpha-hydroxy fatty acids, and
      glucosylceramide 6, phytosphingosine with one double bond and alpha-hydroxy fatty
      acids. The nonhydroxy fatty acids typically have 16-24-carbon-length chains,
      whereas alpha-hydroxy fatty acids are limited to 24-, 25-, and 26-carbon chains.
      The sphingosine bases are C18 or C20 chains. Next, acylglucosylceramides and
      glucosylceramides were treated with beta-glucocerebrosidase and the ceramides
      released were compared with stratum corneum ceramides. Ceramide moieties of
      acylglucosylceramides and glucosylceramides 1, 2, 4-6 correspond to stratum
      corneum ceramides 1-7. These results, together with those of our previous reports
      characterizing epidermal sphingomyelins, indicate that all ceramide species,
      including omega-hydroxy fatty-acid-containing ceramides, are derived from
      glucosylceramides, and fractions of ceramides 2 and 5 are from sphingomyelins.
      Furthermore, structural analysis of glucosylceramides revealed that human
      epidermal glycosphingolipids display a unique lipid profile that is rich in very
      long chain hydroxylated (alpha- and omega-hydroxy) fatty acids and
      phytosphingosine.

PMID- 12190866
TI  - Human keratinocytes express functional CD14 and toll-like receptor 4.
AB  - CD14 and the toll-like receptor 4 have been known to play an important role in
      lipopolysaccharide-induced cellular responses in bacterial infections. Although
      CD14 and toll-like receptor 4 expression has been demonstrated in a number of
      myeloid cells, much less is known about the expression and function of these
      lipopolysaccharide receptors on nonleukocytes. In this study, we demonstrate that
      human keratinocytes are capable of expressing functional CD14 and toll-like
      receptor 4. Keratinocytes were found to constitutively express CD14 and toll-like
      receptor 4 mRNA that was augmented by exposure to lipopolysaccharide. Cell
      surface expression of keratinocyte CD14 and toll-like receptor 4 was detected by
      flow cytometry. Lipopolysaccharide binding to keratinocyte CD14 and toll-like
      receptor 4 resulted in a rapid intracellular Ca2+ response, nuclear factor-kappaB
      nuclear translocation, and the secretion of proinflammatory cytokines and
      chemokines. These results have important implications for our understanding of
      cutaneous innate immunity to bacterial infections of the skin.

PMID- 12190867
TI  - Decreased levels of sphingosine, a natural antimicrobial agent, may be associated
      with vulnerability of the stratum corneum from patients with atopic dermatitis to
      colonization by Staphylococcus aureus.
AB  - The stratum corneum of the skin of patients with atopic dermatitis is highly
      susceptible to colonization by various bacteria, including Staphylococcus aureus.
      The defense system of the skin against bacterial invasion appears to be
      significantly disrupted in atopic dermatitis skin, but little is known about the
      defense mechanism(s) involved. As one sphingolipid metabolite, sphingosine is
      known to exert a potent antimicrobial effect on S. aureus at physiologic levels,
      and it may play a significant role in bacterial defense mechanisms of healthy
      normal skin. Because of the altered ceramide metabolism in atopic dermatitis, the
      possible alteration of sphingosine metabolism might be associated with the
      acquired vulnerability to colonization by S. aureus in patients with atopic
      dermatitis. In this study, we measured the levels of sphingosine in the upper
      stratum corneum from patients with atopic dermatitis, and then compared that with
      the colonization levels of bacteria in the same subjects. Levels of sphingosine
      were significantly downregulated in uninvolved and in involved stratum corneum of
      patients with atopic dermatitis compared with healthy controls. This decreased
      level of sphingosine was relevant to the increased numbers of bacteria including
      S. aureus present in the upper stratum corneum from the same subjects. This
      suggests the possibility that the increased colonization of bacteria found in
      patients with atopic dermatitis may result from a deficiency of sphingosine as a
      natural antimicrobial agent. As for the mechanism involved in the decreased
      production of sphingosine in atopic dermatitis, analysis of the activities of
      ceramidases, major sphingosine-producing enzymes, revealed that, whereas the
      activity of alkaline ceramidase did not differ between patients with atopic
      dermatitis and healthy controls, the activity of acid ceramidase was
      significantly reduced in patients with atopic dermatitis and this had obvious
      relevance to the increased colonization of bacteria in those subjects. Further,
      there was a close correlation between the level of sphingosines and acid
      ceramidase (r = 0.65, p < 0.01) or ceramides (r = 0.70, p < 0.01) in the upper
      stratum corneum from the same patients with atopic dermatitis. Collectively, our
      results suggest the possibility that vulnerability to bacterial colonization in
      the skin of patients with atopic dermatitis is associated with reduced levels of
      a natural antimicrobial agent, sphingosine, which results from decreased levels
      of ceramides as a substrate and from diminished activities of its metabolic
      enzyme, acid ceramidase.

PMID- 12190868
TI  - Cell-cell adhesion and RhoA-mediated actin polymerization are independent
      phenomena in microtubule disrupted keratinocytes.
AB  - E-cadherin-mediated adherens junction formation and maintenance are thought to
      involve actin filament rearrangements through the action of small GTPases.
      Recently, we demonstrated that microtubule disruption in normal human epidermal
      keratinocytes grown in low calcium media conditions induces cell-cell adhesion by
      redistribution of endogenous E-cadherin, and it promotes stress fiber formation.
      This actin rearrangement was apparently mediated by RhoA activation. This model
      system therefore provides a tool with which to dissect relationships between cell
      cell adhesion and Rho-mediated stress fiber formation. In this study, we have
      demonstrated in normal human epidermal keratinocytes that disruption of actin
      structures including stress fibers does not interfere with E-cadherin
      redistribution during microtubule-induced cell-cell adhesion. Moreover, this cell
      cell adhesion could not be blocked by RhoA inactivation at the level for
      inhibition of stress fiber formation. Additionally, in the immortalized HaCaT
      keratinocyte cell line, which does not undergo cell-cell adhesion after
      microtubule disruption in low calcium conditions, expression of dominant-active
      RhoA could induce stress fiber formation without inducing adhesion. On the other
      hand, a variant of the HaCaT cell line, HC-R1, showed microtubule-disruption
      induced cell-cell adhesion without stress fiber formation. Together, our results
      suggest that, in keratinocytes, the process of cell adhesion can occur
      independently of RhoA-mediated stress fiber formation.

PMID- 12190869
TI  - Keratinocytes inhibit expression of connective tissue growth factor in
      fibroblasts in vitro by an interleukin-1alpha-dependent mechanism.
AB  - The wound healing process concludes with downregulation of fibroblast activity.
      Clinical observations suggest that the regenerating epidermis suppresses this
      activity. An important regulator of fibroblast activity is the fibrogenic
      cytokine connective tissue growth factor. We hypothesized that epidermal
      keratinocytes may affect fibroblast activity via this cytokine. We demonstrate
      keratinocyte-mediated suppression of connective tissue growth factor at both the
      mRNA and protein levels by around 50% or more when fibroblasts were cultured in
      multiwell plates with keratinocyte cultures in accompanying semipermeable cell
      culture inserts, or stimulated by keratinocyte-conditioned media. Both basal and
      transforming-growth-factor-beta1-stimulated levels of connective tissue growth
      factor were inhibited. A 3 h coculture period with keratinocytes was sufficient
      to suppress connective tissue growth factor expression by fibroblasts, but the
      inhibition developed over a time period of around 16 h. The putative keratinocyte
      derived factor(s) responsible for these effects was found to be soluble and
      stable. By analyzing cytokines secreted by keratinocytes we identified
      interleukin-1alpha as a potent inhibitor of connective tissue growth factor mRNA
      expression in fibroblasts. Involvement of this cytokine in keratinocyte-mediated
      connective tissue growth factor suppression was confirmed by using anti
      interleukin-1alpha antibodies. Tumor necrosis factor alpha or prostaglandins did
      not appear to be involved. In conclusion, our results indicate that interleukin
      1alpha secretion by keratinocytes provides a mechanism for the downregulation of
      connective tissue activity during the end-stage of wound healing, when epithelia
      coverage has developed over the wound area.

PMID- 12190870
TI  - Latent and active transforming growth factor beta1 released from genetically
      modified keratinocytes modulates extracellular matrix expression by dermal
      fibroblasts in a coculture system.
AB  - Transforming growth factor beta1 is a multifunctional cytokine involved in many
      aspects of wound healing. Here we report the effects of both latent and active
      transforming growth factor beta1 released from genetically modified keratinocytes
      on extracellular matrix expression by dermal fibroblasts in a coculture system.
      Human keratinocytes were genetically modified with adenovirus containing cDNA for
      latent transforming growth factor beta1 (AdTGF-beta1) or active transforming
      growth factor beta1 (AdTGF-beta1(223/225)) or LacZ and cultured with human dermal
      fibroblasts. Northern blotting for mRNA confirmed that keratinocytes were
      successfully transduced with the adenoviruses as the cDNA transcripts are smaller
      than native transforming growth factor beta1 mRNA. An enzyme-linked immunosorbent
      assay specific for transforming growth factor beta1 demonstrated that the
      transforming growth factor beta1 produced by the genetically modified
      keratinocytes was able to pass through the membrane separating the two cell
      layers. Levels of transforming growth factor beta1 were significantly higher for
      both latent (p < 0.0001) and active (p < 0.0001) transforming growth factor beta1
      compared to the LacZ control. Without acid activation of samples, keratinocytes
      transduced with the active transforming growth factor beta1 construct exhibited
      significantly higher levels of transforming growth factor beta1 than either the
      latent construct or the LacZ control (p < 0.0001). The transforming growth factor
      beta1 produced was biologically active, as shown by the plasminogen activator
      inhibitor assay (p < 0.0001). To demonstrate that transforming growth factor
      beta1 had an effect on underlying fibroblasts, mRNA was extracted and analyzed
      using Northern analysis. Latent transforming growth factor beta1 significantly
      increased the expression of type I collagen mRNA (p < 0.05) but did not
      significantly affect collagenase mRNA. Active transforming growth factor beta1
      significantly increased type I collagen mRNA (p < 0.005) while also decreasing
      collagenase mRNA (p < 0.05). These results illustrate the ability of increased
      levels of transforming growth factor beta1 to override the effects of normal
      keratinocytes on the behavior of dermal fibroblasts.

PMID- 12190871
TI  - Zinc alpha-2-glycoprotein regulates melanin production by normal and malignant
      melanocytes.
AB  - Zinc alpha-2-glycoprotein is secreted by a variety of normal and malignant
      epithelial cells and overexpression by tumors has been implicated in cancer
      cachexia. To investigate biologic properties of zinc alpha-2-glycoprotein
      further, stable transfectants of recombinant human zinc alpha-2-glycoprotein were
      created in the B16F10 murine melanoma cell line. Both B16-recombinant human zinc
      alpha-2-glycoprotein clones with strong expression of zinc alpha-2-glycoprotein
      and vector-transfected B16 cells treated with exogenous zinc alpha-2-glycoprotein
      had decreased melanin production in vitro. Furthermore, B16-recombinant human
      zinc alpha-2-glycoprotein clones formed amelanotic tumors in vivo, despite their
      melanin production in vitro. Although no qualitative differences in tyrosinase
      mRNA expression could be detected by reverse transcription-polymerase chain
      reaction, B16-recombinant human zinc alpha-2-glycoprotein tumors had decreased
      levels of tyrosinase protein and minimal tyrosinase activity. Purified zinc alpha
      2-glycoprotein also decreased tyrosinase activity in vector-transfected B16 tumor
      sections in vitro. Taken together, these studies demonstrate that zinc alpha-2
      glycoprotein inhibits melanin production by B16 melanoma cells via post
      transcriptional effects on tyrosinase protein. As zinc alpha-2-glycoprotein
      decreases melanin synthesis more strongly in vivo than in vitro, however, it is
      likely that zinc alpha-2-glycoprotein affects melanin synthesis through indirect
      mechanisms as well. Zinc alpha-2-glycoprotein also inhibits melanin production by
      melan-A primary melanocytes in vitro. As zinc alpha-2-glycoprotein is normally
      produced by epidermal keratinocytes, these studies raise the possibility that
      epidermal-derived zinc alpha-2-glycoprotein may play a part in normal regulation
      of melanin production in vivo, in addition to its previously described role in
      cancer cachexia.

PMID- 12190872
TI  - Digital dermoscopy analysis and artificial neural network for the differentiation
      of clinically atypical pigmented skin lesions: a retrospective study.
AB  - Noninvasive diagnostic methods such as dermoscopy or epiluminescence light
      microscopy have been developed in an attempt to improve diagnostic accuracy of
      pigmented skin lesions. The evaluation of the many morphologic characteristics of
      pigmented skin lesions observable by epiluminescence light microscopy, however,
      is often extremely complex and subjective. With the aim of obviating these
      problems of qualitative interpretation, methods based on mathematical analysis of
      pigmented skin lesions have recently been designed. These methods are based on
      computerized analysis of digital images obtained by epiluminescence light
      microscopy. In this study we used a digital dermoscopy analyzer with 147
      clinically atypical pigmented skin lesions (90 nevi and 57 melanomas) to
      determine its discriminating power with respect to histologic diagnosis. The
      system evaluated 48 objective parameters used to train an artificial neural
      network. Using the artificial neural network with 10 variables selected by a
      stepwise procedure, we obtained a maximum accuracy in distinguishing melanoma
      from benign lesions of about 93%. Comparing this result with those of the many
      studies using classical epiluminescence light microscopy, it emerges that the
      method proposed is equal or even superior in diagnostic accuracy and has the
      advantage of not depending on the expertise of the clinician who examines the
      lesion.

PMID- 12190873
TI  - Tyrosinase and tyrosinase-related protein 1 require Rab7 for their intracellular
      transport.
AB  - We have recently identified the association of Rab7 in melanosome biogenesis and
      proposed that Rab7 is involved in the transport of tyrosinase-related protein 1
      from the trans-Golgi network to melanosomes, possibly passing through late
      endosome-delineated compartments. In order to further investigate the requirement
      of Rab7-containing compartments for vesicular transport of tyrosinase family
      proteins, we expressed tyrosinase and tyrosinase-related protein by recombinant
      adenovirus and analyzed their localization in human amelanotic melanoma cells (SK
      mel-24) in the presence or absence of a dominant-negative mutant of Rab7
      (Rab7N125I). Co-infection of the recombinant adenoviruses carrying tyrosinase (Ad
      HT) and TRP-1 (Ad-TRP-1) resulted in the enhancement of tyrosinase activity and
      melanin production compared to a single infection of Ad-HT. In the Ad-HT-infected
      SK-mel-24 cells many of the newly synthesized tyrosinase proteins were
      colocalized in lysosomal lgp85-positive granules of the entire cytoplasm, whereas
      in the presence of Rab7N125I the colocalization of tyrosinase and lgp85 proteins
      was decreased markedly in the distal area of the cytoplasm. In the Ad-TRP-1
      infected SK-mel-24 cells, TRP-1, which is reported to be present exclusively in
      melanosomes, was detected throughout the cytoplasm, but not colocalized in
      prelysosomal (early endosomal) EEA-1 granules. In the presence of Rab7N125I,
      however, TRP-1 was retained in the EEA-1-positive granules. Our findings indicate
      that the dominant-negative mutant of Rab7 impairs vesicular transport of
      tyrosinase and TRP-1, suggesting that the transport of these melanogenic proteins
      from the trans-Golgi network to maturing melanosomes requires passage through
      endosome-delineated compartments.

PMID- 12190874
TI  - Coexpression of wild-type tyrosinase enhances maturation of temperature-sensitive
      tyrosinase mutants.
AB  - Tyrosinase is a type I membrane glycoprotein whose activity is essential for
      melanin synthesis. Loss of function mutations in tyrosinase is the cause of
      oculocutaneous albinism 1. In the milder oculocutaneous albinism 1B form in which
      mutant proteins retain residual activity, the severity of albinism depends on the
      type of mutations expressed in the melanocyte. In this study, we show that
      coexpression of wild-type protein with temperature-sensitive tyrosinase mutants
      corrects the mutant conformation defect in an activity-dependent manner. Exit
      from the endoplasmic reticulum and complex carbohydrate processing in the Golgi
      was promoted when temperature-sensitive tyrosinase mutants were ectopically
      expressed in host melanocytes carrying wild-type protein even at the
      nonpermissive temperature. Incubation of transfected melanocytes with DOPA (the
      cofactor and substrate for tyrosinase), or tyrosine (the substrate), further
      enhanced processing of ectopic mutant proteins. The analysis of glycosylation
      deficient mutants revealed regions in tyrosinase with high, low, and intermediate
      dependency on glycans for maturation. We concluded that the presence of
      tyrosinase activity enhances the maturation of temperature-sensitive and
      glycosylation-deficient forms of tyrosinase. The results may explain the
      variation in pigmentation and the development of pigment later in life in
      patients carrying different mutant alleles of oculocutaneous albinism 1B.

PMID- 12190875
TI  - Photosensitized growth inhibition of cultured human skin cells: mechanism and
      suppression of oxidative stress from solar irradiation of glycated proteins.
AB  - Chronic exposure to sunlight plays a role in skin aging and carcinogenesis. The
      molecular mechanisms of photodamage by ultraviolet A, the sunlight's major
      ultraviolet constituent, are poorly understood. Here we provide evidence that
      advanced glycation end products on proteins are sensitizers of photo-oxidative
      stress in skin cells. Glycation is a process of protein damage by reducing sugars
      and other reactive carbonyl species leading to the formation of advanced
      glycation end products, which accumulate on long-lived proteins such as dermal
      elastin and collagen during skin aging. Growth inhibition as a result of advanced
      glycation end product photosensitization of ultraviolet A and solar-simulated
      light was demonstrated in human keratinocytes and fibroblasts. Using advanced
      glycation end product bovine serum albumin and advanced glycation end product
      collagen as model photosensitizers, ultraviolet A-induced formation of H2O2 was
      identified as the key mediator of skin cell growth inhibition as evidenced by
      complete protection by catalase treatment and equivalent growth inhibition of
      unirradiated cells treated with pre-irradiated advanced glycation end product
      protein. D-penicillamine protected against advanced glycation end product
      photosensitized growth inhibition even when added following irradiation,
      suggesting the feasibility of therapeutic approaches for protection against skin
      ultraviolet A damage. Photosensitized growth inhibition increased with the degree
      of advanced glycation end product modification paralleled by the amount of H2O2
      formed upon solar-simulated light irradiation of the protein. Photosensitization
      was not observed using bovine serum albumin modified with the major advanced
      glycation end product, Nepsilon-carboxymethyl-L-lysine, ruling out effects of
      cellular advanced glycation end product receptor (RAGE) stimulation. In contrast
      to bovine serum albumin, unglycated collagen showed photosensitization in CF3
      fibroblasts and generation of H2O2 upon solar-simulated light irradiation. This
      study supports the hypothesis that advanced glycation end product-modified
      proteins are endogenous sensitizers of photo-oxidative cell damage in human skin
      by ultraviolet A-induced generation of reactive oxygen species contributing to
      photoaging and photocarcinogenesis.

PMID- 12190876
TI  - Ultraviolet irradiation alters transforming growth factor beta/smad pathway in
      human skin in vivo.
AB  - Solar ultraviolet irradiation damages human skin and causes premature skin aging
      and skin cancer. As transforming growth factor beta plays an important role in
      regulating cell growth and extracellular matrix synthesis, we investigated
      expression of transforming growth factor beta isoforms, transforming growth
      factor beta receptors, and transforming growth factor beta regulated Smad
      transcription factors following irradiation with an ultraviolet B source and
      solar-simulated ultraviolet irradiation of human skin in vivo. Full-thickness,
      sun-protected adult human skin expressed transforming growth factor beta1, beta2,
      and beta3 transcripts in a ratio of 1:5:3, as determined by quantitative real
      time reverse transcription polymerase chain reaction. Northern analysis
      demonstrated that the ultraviolet irradiation (2 minimal erythema dose) caused
      moderate (2-3-fold) gradual increases of transforming growth factor beta1 and
      beta3 mRNA expression during 3 d post exposure. In contrast, expression of
      transforming growth factor beta2 mRNA, the predominant form of transforming
      growth factor beta in human skin, decreased within 4 h after ultraviolet
      irradiation. In situ hybridization revealed transforming growth factor beta1,
      beta2, and beta3 mRNA expression in cells throughout the epidermis and the dermis
      in nonirradiated skin. Following ultraviolet or solar-simulated ultraviolet
      irradiation, transforming growth factor beta1 and beta3 mRNA were increased and
      transforming growth factor beta2 mRNA was reduced throughout the epidermis and
      dermis. No significant changes were observed in transforming growth factor beta
      type I receptor mRNA expression after ultraviolet irradiation. In contrast,
      transforming growth factor beta type II receptor mRNA expression was reduced 60%
      within 4 h following ultraviolet exposure in human skin in vivo. Transforming
      growth factor beta type II receptor mRNA levels remained reduced for 8 h and
      recovered by 24 h post ultraviolet. In situ hybridization revealed that
      ultraviolet or solar-simulated ultraviolet irradiation caused loss of
      transforming growth factor beta type II receptor mRNA in basal and suprabasal
      cells in the epidermis and dermal cells. In addition, no significant changes were
      observed in Smad2, Smad3, and Smad4 expression after ultraviolet irradiation. In
      contrast, ultraviolet and solar-simulated ultraviolet irradiation rapidly induced
      gene expression of Smad7, which antagonizes the actions of the transforming
      growth factor beta/Smad pathway. Smad7 mRNA induction occurred throughout the
      epidermis and dermal cells as determined by in situ hybridization. Ultraviolet
      irradiation also caused reduced DNA binding of Smad3/4 in human skin in vivo.
      Reduced Smad3/4 DNA binding was observed within 4 h following irradiation. Taken
      together, these results demonstrate that ultraviolet and solar-simulated
      ultraviolet irradiation alter the transforming growth factor beta/Smad pathway in
      human skin in vivo. Ultraviolet induction of Smad7 and reduction of transforming
      growth factor beta2 and transforming growth factor beta type II receptor should
      diminish transforming growth factor beta signaling, and probably contribute to
      the decrease of transforming growth factor beta regulated type I and type III
      procollagen gene expression observed in ultraviolet and solar-simulated
      ultraviolet irradiated human skin in vivo.

PMID- 12190878
TI  - Role of p21(Waf-1) in regulating the G1 and G2/M checkpoints in ultraviolet
      irradiated keratinocytes.
AB  - This study examines the role of p21(Waf-1) , a p53-dependent protein, in
      regulating mechanisms that protect keratinocytes against ultraviolet-B-induced
      cellular damage. Keratinocytes from p21(Waf-1) or p53-deficient mice were
      irradiated with ultraviolet B, and examined for DNA repair, cell cycle
      progression, and cell death. Both p21(Waf-1) -deficient and p53-deficient cells
      failed to maintain G2 arrest, and p21(Waf-1) -deficient cells, and to a lesser
      extent p53-deficient cells, also failed to undergo G1 arrest. After exposure to
      ultraviolet B, p53-deficient cells were more susceptible to cell death than wild
      type cells. p21(Waf-1) -deficient cells did not undergo apoptotic cell death more
      often, however, but did have an increased frequency of nuclear abnormalities,
      suggesting mitotic catastrophe. TUNEL assay showed DNA fragmentation in the p53
      +/+, p21(Waf-1) +/+, and p53 -/- cells, but not in p21(Waf-1) -/- cells. This
      result is consistent with the suggestion that p21(Waf-1) -deficient keratinocytes
      undergo mitotic cell death (catastrophe) after exposure to ultraviolet B
      irradiation in the system. Western analysis demonstrated that p21(Waf-1)
      expression was upregulated in p53-proficient and -deficient keratinocytes,
      supporting the notion that a p53-independent mechanism contributes to the
      response to ultraviolet B in keratinocytes. Finally, p21(Waf-1) -deficient cells
      had slightly less efficient nucleotide excision repair. In summary, this study
      suggests that p21(Waf-1) regulates the ultraviolet-B-induced G2/M checkpoint
      through p53, and the G1 checkpoint partially through p53. p21(Waf-1) does not
      significantly regulate DNA repair in ultraviolet-irradiated keratinocytes,
      however.

PMID- 12190877
TI  - Ultraviolet modulation of human macrophage metalloelastase in human skin in vivo.
AB  - Human macrophage metalloelastase is a member of the matrix metalloproteinase
      family and is involved in degradation of elastin. We investigated the ultraviolet
      modulation of human macrophage metalloelastase in human skin in vivo. Ultraviolet
      induced human macrophage metalloelastase mRNA maximally (11.9-fold) within 16 h
      post-ultraviolet in human skin. This induction of human macrophage
      metalloelastase by ultraviolet was inhibited by pretreatment with the antioxidant
      N-acetyl cystein (20%) and vitamin E (5%) by an average of 54% and 47%,
      respectively, in human skin in vivo. Ultraviolet (30 mJ per cm2) and phorbol
      ester (12-O-tetradecanoyl-phorbol-13-acetate, 50 nM) treatment increased
      expression of human macrophage metalloelastase mRNA and protein in the cultured
      human dermal fibroblasts, but not in the keratinocytes. Chronically sun-exposed
      human skin expressed significant amounts of human macrophage metalloelastase
      protein, which colocalized with the material of solar elastosis, whereas there
      was little expression in sun-protected skin of the same individuals. This study
      demonstrates that ultraviolet irradiation increases human macrophage
      metalloelastase expression in human skin in vivo, possibly in macrophages and
      fibroblasts, and ultraviolet-induced expression of human macrophage
      metalloelastase can be inhibited by antioxidant (N-acetyl cystein and vitamin E)
      pretreatment. Association of human macrophage metalloelastase with elastotic
      material suggests that it may play an important role in the development of solar
      elastosis, the hallmark of sun-induced damage in human skin in vivo.

PMID- 12190879
TI  - p53 mutation in nonmelanoma skin cancers occurring in psoralen ultraviolet a
      treated patients: evidence for heterogeneity and field cancerization.
AB  - A combination of psoralens and ultraviolet A radiation is widely used to treat
      psoriasis. Long-term, high-dose exposure to psoralen + ultraviolet A is
      associated with an increased risk of nonmelanoma skin cancer, particularly
      squamous cell carcinoma. In this study, we used p53 mutations as a molecular
      marker to determine the separate contributions of psoralen + ultraviolet A and
      other ultraviolet exposures, such as ultraviolet B for skin cancer development in
      psoralen + ultraviolet A-treated psoriasis patients. The results indicated that
      of 69 tumors analyzed, 37 (54%) tumors had one or more p53 mutations. Of 37
      tumors with mutations, 17 (46%) tumors had only ultraviolet-type mutations, two
      (5%) tumors had only psoralen + ultraviolet A-type mutations, and 18 (49%) tumors
      had both types of mutations. Interestingly, psoralen + ultraviolet A-type p53
      mutations were more frequent than ultraviolet type in tumors arising in patients
      with high-dose exposure to psoralen + ultraviolet A. Field cancerization and
      tumor heterogeneity appeared to occur frequently in the same patient and even in
      the same tumor. This study's data suggest that psoralen + ultraviolet A-induced
      p53 mutations may play an important part in the development of nonmelanoma skin
      cancer in psoralen + ultraviolet A-treated patients, but these mutations are
      likely to act in concert with the effects of other carcinogenic exposures,
      particularly ultraviolet B, in the development of skin cancer.

PMID- 12190880
TI  - Phenotype diversity in familial cylindromatosis: a frameshift mutation in the
      tumor suppressor gene CYLD underlies different tumors of skin appendages.
AB  - Familial cylindromatosis (turban tumor syndrome; Brooke-Spiegler syndrome) (OMIM
      numbers 123850, 132700, 313100, and 605041) is a rare autosomal dominantly
      inherited tumor syndrome. The disorder can present with cutaneous adnexal tumors
      such as cylindromas, trichoepitheliomas, and spiradenomas, and tumors preferably
      develop in hairy areas of the body such as head and neck. In affected families,
      mutations have been demonstrated in the CYLD gene located on chromosome 16q12-13
      and reveal the characteristic attributes of a tumor suppressor. Here, we studied
      familial cylindromatosis in a multigeneration family of German origin.
      Clinically, some individuals only revealed discrete small skin-colored tumors
      localized in the nasolabial region whereas one family member showed expansion of
      multiple big tumors on the trunk and in a turban-like fashion on the scalp.
      Histologically, cylindromas as well as epithelioma adenoides cysticum were found.
      We detected a frameshift mutation in the CYLD gene, designated 2253delG,
      underlying the disorder and were able to show that a single mutation can result
      in distinct clinical and histologic expression in familial cylindromatosis. The
      reasons for different expression patterns of the same genetic defect in this
      disease remain elusive, however. Identification of mutations in the CYLD gene
      enable us to rapidly confirm putative diagnoses on the genetic level and to
      provide affected families with genetic counseling.

PMID- 12190881
TI  - Apolipoprotein E4 is associated with primary localized cutaneous amyloidosis.

PMID- 12190882
TI  - Real-time, in vivo quantification of melanocytes by near-infrared reflectance
      confocal microscopy in the Guinea pig animal model.

PMID- 12190883
TI  - Exclusion of candidate genes and loci for multiple lentigines syndrome.

PMID- 12190884
TI  - Evolution and spread of antibiotic resistance.
AB  - Antibiotic resistance is a clinical and socioeconomical problem that is here to
      stay. Resistance can be natural or acquired. Some bacterial species, such as
      Pseudomonas aeruginosa, show a high intrinsic resistance to a number of
      antibiotics whereas others are normally highly antibiotic susceptible such as
      group A streptococci. Acquired resistance evolve via genetic alterations in the
      microbes own genome or by horizontal transfer of resistance genes located on
      various types of mobile DNA elements. Mutation frequencies to resistance can vary
      dramatically depending on the mechanism of resistance and whether or not the
      organism exhibits a mutator phenotype. Resistance usually has a biological cost
      for the microorganism, but compensatory mutations accumulate rapidly that abolish
      this fitness cost, explaining why many types of resistances may never disappear
      in a bacterial population. Resistance frequently occurs stepwise making it
      important to identify organisms with low level resistance that otherwise may
      constitute the genetic platform for development of higher resistance levels. Self
      replicating plasmids, prophages, transposons, integrons and resistance islands
      all represent DNA elements that frequently carry resistance genes into sensitive
      organisms. These elements add DNA to the microbe and utilize site-specific
      recombinases/integrases for their integration into the genome. However,
      resistance may also be created by homologous recombination events creating mosaic
      genes where each piece of the gene may come from a different microbe. The
      selection with antibiotics have informed us much about the various genetic
      mechanisms that are responsible for microbial evolution.

PMID- 12190885
TI  - Adulteration of Chinese herbal medicines with synthetic drugs: a systematic
      review.
AB  - The popularity of Chinese herbal medicines (CHMs) demands a critical analysis of
      safety issues. The aim of this systematic review is to summarize data regarding
      adulterations of CHMs with conventional drugs. Literature searches were carried
      out in six databases. Articles containing original data on adulterations were
      considered without language restrictions. Eighteen case reports, two case series
      and four analytical investigations were identified. The list of adulterants
      contains drugs associated with serious adverse effects like corticosteroids. In
      several instances, patients were seriously harmed. One report from Taiwan
      suggests that 24% of all samples were contaminated with at least one conventional
      pharmacological compound. It is concluded that adulteration of CHMs with
      synthetic drugs is a potentially serious problem which needs to be addressed by
      adequate regulatory measures.

PMID- 12190886
TI  - Carotid artery intima-media thickness and brachial artery flow-mediated
      vasodilation in asymptomatic Japanese male subjects amongst apolipoprotein E
      phenotypes.
AB  - BACKGROUND: Epidemiological studies suggest that apolipoprotein E (apoE)
      polymorphism influences plasma lipoprotein levels and the development of
      cardiovascular disease. OBJECTIVE: To clarify the role of apoE polymorphism as a
      risk factor for early atherosclerosis. DESIGN: Using a high-resolution ultrasound
      method, we investigated the association between apoE phenotypes, carotid intima
      media thickness (CCA-IMT), and flow-mediated dilation in the brachial artery
      (brachial-FMD) in 96 healthy asymptomatic Japanese men (mean +/- SD age, 50 +/- 8
      years). RESULTS: Serum cholesterol and LDL-cholesterol levels in subjects with
      E3E4 were highest and those with E2E3 were lowest (P < 0.05 and P < 0.05,
      respectively). The CCA-IMT in E3E4 subjects (0.76 +/- 0.17 mm) was greater than
      that in E2E3 and E3E3 (0.61 +/- 0.15 and 0.64 +/- 0.14 mm, respectively; P <
      0.01). In contrast, there was no difference between brachial-FMD and apoE
      phenotypes (P=0.15). By univariate analysis, CCA-IMT was positively correlated
      with age (r=0.51, P < 0.01), LDL-chol/HDL-chol ratio (r=0.37, P < 0.01),
      triglycerides (r=0.23, P < 0.05), and negatively correlated with HDL-cholesterol
      (r=-0.31, P < 0.01). An association between CCA-IMT and the presence of E4 allele
      was also found (P < 0.05). Logistic regression analysis revealed that the
      presence of E4 allele was a higher risk for increased IMT (relative risk of 4.4,
      95% CI 1.5-12.5), even after adjustment for age, LDL-cholesterol, blood pressure
      and other known risk factors. A negative correlation between brachial-FMD and CCA
      IMT was also found in all subjects (r=-0.21, P < 0.05), being most apparent in
      the E3E4 subjects (r=-0.53, P < 0.02). CONCLUSION: ApoE4 phenotype was
      independently associated with an increased risk of carotid atherosclerosis and
      elevated LDL-cholesterol levels in asymptomatic middle-aged Japanese men.

PMID- 12190887
TI  - A new classification tool for clinical differentiation between haemorrhagic and
      ischaemic stroke.
AB  - PURPOSE: To develop a simple and reliable diagnostic tool for differentiation of
      cerebral infarction (CIF) from intracerebral haemorrhage (ICH) in order to aid
      clinicians to decide about starting antiplatelet therapy in settings where rapid
      access to computed tomography (CT) is lacking. METHODS: Thirty variables
      regarding each patient admitted with acute stroke were recorded and considered in
      a logistic regression analysis using ICH as end-point (internal study). CT was
      used as the golden standard. The score derived was validated with data from the
      next consecutive stroke patients and was compared with the three preexisting
      scores (external validation study). RESULTS: Amongst 235 patients (119 males,
      mean age 70.6 +/- 11.2 years) of the internal study, 43 (18.3%) had ICH. Four
      independent correlates of ICH were identified and used for the derivation of the
      following integer-based scoring system: number of points=6 * (neurological
      deterioration within 3 h from admission) + 4 * (vomiting) + 4 * (WBC > 12 000) +
      3 * (decreased level of consciousness). In the external study [168 patients, 85
      males, mean age 70.2 +/- 10.8 years, 31 (18.5%) with ICH], when the cut-offs < or
      =3 points for CIF and > or =11 points for ICH were used, sensitivity,
      specificity, and positive and negative predictive values of the score for
      detection of stroke type were 97, 99, 97 and 99%, respectively; exceeding
      noticeably the three previously proposed systems. CONCLUSIONS: The proposed model
      provides an easy to use tool for sufficiently accurate differentiation between
      haemorrhagic and nonhaemorrhagic stroke on the basis of information available to
      all physicians early after admission.

PMID- 12190888
TI  - Effects of cigarette smoking or nicotine replacement on cardiovascular risk
      factors and parameters of haemorheology.
AB  - OBJECTIVES: Cigarette smoking causes cardiovascular (CV) disease, but the
      relative roles of nicotine and other components of tobacco smoke remain unclear.
      We investigated the effect of stopping smoking, by using nicotine replacement
      therapy (NRT), on haemorheology parameters. DESIGN: Open, parallel-group trial
      (intervention group and control smokers). SETTING: Clinic within university
      department of pharmacology. SUBJECTS: One hundred and ninety-seven males, aged 25
      45 years, smoking >20 cigarettes per day. INTERVENTIONS: One hundred and sixty
      four subjects were instructed to stop smoking and received NRT for 12 weeks and
      33 acted as controls. After 12 weeks, NRT was discontinued, and all subjects were
      followed-up at 26 weeks. At the end of the study, the NRT group was divided into
      abstainers (self-reported, verified by exhaled carbon monoxide <10 ppm) and
      relapsers, who were unable to remain abstinent. MAIN OUTCOME MEASURES: Plasma
      viscosity, fibrinogen, erythrocyte deformability, reactive capillary blood flow,
      transcutaneous partial oxygen tension (tcpO2) and haematocrit, assessed at 4, 8,
      12, and 26 weeks. Results. After 6 months, plasma fibrinogen (9.95 vs. 8.24
      micromol x L(-1) at baseline; P < 0.003), reactive capillary flow (t-pmax: 9.3
      vs. 11.2 s at baseline; P < 0.005), and tcpO2 (50.4 vs. 34.9 mmHg at baseline; P
      < 0.0001) were significantly improved in abstainers, but changes in plasma
      viscosity and erythrocyte deformability were inconclusive. Other CV risk factors,
      such as haematocrit and white blood cell count, decreased to a greater extent in
      abstainers than in relapsers. Expired carbon monoxide concentrations reflected
      the changes in smoking and decreased in abstainers from 30.4 ppm at baseline to
      4.2 ppm; P < 0.0001). Conclusions. Smoking cessation improved CV parameters, and
      use of nicotine medications did not negate these improvements.

PMID- 12190889
TI  - The association between leptin and proinsulin is lost with central obesity.
AB  - OBJECTIVE: Hyperproinsulinaemia and hyperleptinaemia are interrelated features of
      the insulin resistance syndrome that are linked to the prospective risk of
      cardiovascular diseases. Whether the association between leptin and proinsulin is
      different between groups displaying different degrees of risk for cardiovascular
      diseases is not known. We therefore examined this association in men versus women
      and in pre- versus postmenopausal women from a population-based sample. DESIGN
      AND SUBJECTS: Healthy subjects (n = 158; 85 men and 73 pre- and postmenopausal
      women) from the Northern Sweden Monitoring of Trends and Determinants in
      Cardiovascular Disease population were studied with a cross-sectional design.
      METHODS: Anthropometric measurements (body mass index and waist circumference)
      and oral glucose tolerance tests were performed. Enzyme-linked immunosorbent
      assays were used for the analyses of specific insulin and proinsulin, and
      radioimmunoassay for leptin. Insulin resistance and beta-cell function were
      calculated according to the homeostasis assessment model. Partial correlation
      coefficients adjusted for age and measures of adiposity were calculated and
      multiple linear regression analyses were performed with leptin as dependent
      variable. RESULTS: In nonobese men and premenopausal women and in obese
      postmenopausal women, leptin was significantly associated with proinsulin after
      stratification for waist circumference. Furthermore, a multivariate analyses
      taking age and measures of adiposity into account, showed that high fasting
      proinsulin was a significant predictor of high leptin in these groups. In
      contrast, this association was lost with increasing central obesity in men and
      premenopausal women. CONCLUSIONS: This study shows that both the degree of
      adiposity and the hormonal milieu influence the association between circulating
      leptin and proinsulin in a normal population. Therefore, the insulin resistance
      syndrome seems to be characterized by lost association between leptin and
      proinsulin, which may be explained by dysfunction in the adipoinsular axis.

PMID- 12190890
TI  - Risk factors for thrombosis in patients with immune mediated heparin-induced
      thrombocytopenia.
AB  - BACKGROUND: As reported by major clinical series in the literature, about 2% of
      patients receiving unfractionated heparin (UFH) develop immune-mediated (type II)
      heparin-induced thrombocytopenia (HIT) that may be complicated in 30-75% of cases
      by a paradoxical thrombotic syndrome (HITTS), either arterial or venous. HITTS
      carries relevant rates of mortality and morbidity, amongst which cerebral and/or
      myocardial infarction and limb amputations. It is unclear as yet why some
      patients suffer from isolated thrombocytopenia (HIT), whilst others have HITTS.
      The aim of the present study was to look for clinical and laboratory features
      related to the occurrence of HITTS. PATIENTS AND METHODS: We retrospectively
      analysed the clinical records of 56 patients with proven HIT, as diagnosed on
      clinical grounds and by in vitro demonstration of immunoglobulin (IgG)/IgM
      against the PF4/heparin complex. Thirty-four patients (61%) had HITTS (19 venous
      thrombosis, seven arterial thrombosis, five arterial and venous thrombosis, two
      skin necrosis, one diffuse intravascular coagulation), whereas 22 had
      uncomplicated HIT. Amongst HITTS patients, two had limb amputation, five had
      recurrent thrombosis and seven died. Amongst HIT patients three died from causes
      unrelated to HIT. RESULTS: No significant difference in sex, age, previous
      exposure to heparin, UFH route of administration or dose, duration of therapy,
      time of onset of thrombocytopenia and platelet count recovery, nor
      antiheparin/PF4 antibodies subtype (IgG or IgM) was detected when comparing HIT
      and HITTS. In contrast, in the HITTS group a higher prevalence of orthopaedic
      surgery (15 of 34 vs. 2/22; P=0.01), a significantly lower platelet count nadir
      (43 +/- 32 vs. 75 +/- 63 x 109/L; P=0.01) and a significantly higher titre of
      antiheparin/PF4 antibodies, expressed as optical density of enzyme-linked
      immunosorbent assay (ELISA); (1989 +/- 1024 vs. 1277 +/- 858; P=0.009), were
      observed in comparison with the HIT group. Amongst HITTS patients, the prevalence
      of venous thrombosis was significantly higher in orthopaedic patients and in
      those being treated for venous thromboembolism (18/24 vs. 1/9 patients, chi2 8.4,
      P=0.004), whilst arterial thrombosis (ART) occurred more often in heparin
      treatment for arterial disease (3/4 vs. 4/29 patients, chi2 4.6, P=0.03).
      CONCLUSIONS: Orthopaedic surgery, the severity of thrombocytopenia and high
      antiheparin/PF4 antibodies titre are adverse prognostic or concurrent factors in
      the development of HITTS.

PMID- 12190891
TI  - Insulin resistance is accompanied by increased von Willebrand factor levels in
      nondiabetic women: a study of offspring of type 2 diabetic subjects compared to
      offspring of nondiabetic subjects.
AB  - OBJECTIVES: To examine whether levels of von Willebrand factor (vWF), fibrinogen
      and fibronectin are related to a parental history of type 2 diabetes and to
      determine possible explanatory factors for high versus low vWF and fibrinogen.
      DESIGN: Cross-sectional study. SUBJECTS, MAIN OUTCOME MEASURES: We compared vWF,
      fibrinogen and fibronectin in 88 nondiabetic offspring of type 2 diabetic
      subjects (relatives) and 103 offspring of nondiabetic subjects (controls). Other
      measurements included urinary albumin excretion rate, blood pressure, lipid
      profile and insulin resistance using homeostasis model assessment (HOMAIR).
      RESULTS: There were no significant differences in vWF (1.12 vs. 1.06 IU x mL(-1),
      P = 0.296), fibrinogen (3.2 vs. 3.1 g x L(-1); P = 0.263) or fibronectin (0.39
      vs. 0.40 g x L(-1), P = 0.448) between relatives and controls. With multiple
      logistic regression we determined explanatory factors for high versus low vWF and
      fibrinogen. Age (P < 0.01), urinary albumin excretion rate (P < 0.05), ischaemic
      heart disease (IHD) (P < 0.05) were found to be significant explanatory factors
      for vWF above the median (1.10 IU x mL(-1)). Interaction between insulin
      resistance and sex was found. Odds ratio for high versus low insulin resistance
      was 18.39 (P < 0.001) for women and 1.92 (P = 0.32) for men. Body mass index
      (BMI) (P < 0.05), sex (P < 0.01), smoking status (P < 0.05) and IHD (P < 0.01)
      were significant explanatory factors for fibrinogen above the median (3.1 g x L(
      1)). CONCLUSIONS: Levels of vWF, fibrinogen and fibronectin were not influenced
      by a parental history of type 2 diabetes. Insulin resistance was found to be a
      significant risk indicator for high vWF only in women. This may indicate that
      insulin resistance is a higher risk factor for women than for men, when the
      outcome is endothelial dysfunction possibly resulting in overt cardiovascular
      disease.

PMID- 12190892
TI  - Microalbuminuria, cardiovascular disease and risk factors in a
      nondiabetic/nonhypertensive population. The Nord-Trondelag Health Study (HUNT,
      1995-97), Norway.
AB  - OBJECTIVE: Microalbuminuria (MA) as an independent marker of cardiovascular
      morbidity and mortality in nondiabetic/nonhypertensive individuals is under
      international debate. The aim of this study was to investigate the associations
      between MA and known cardiovascular risk factors/markers and disease in a
      randomly selected nondiabetic/nonhypertensive sample. DESIGN: Cross-sectional
      study. SETTING: Participants in the population-based Nord-Trondelag Health Study
      (HUNT), Norway (n = 65 258). SUBJECTS: A total of 2113 individuals (> or =20
      years), randomly selected without diabetes and treated hypertension, delivered
      three morning urine samples for MA analysis. MAIN OUTCOME MEASURES: MA expressed
      as albumin-to-creatinine ratio (ACR), cardiovascular risk factors and disease.
      RESULTS: Increasing age, pulse pressure, systolic (SBP) and diastolic blood
      pressure (DBP) and coronary heart disease (CHD) significantly predicted MA in men
      and increasing pulse pressure, SBP and DBP were associated with MA in women,
      adjusted for other cardiovascular risk factors/markers. After excluding
      individuals with known CHD and untreated hypertension (SBP > or = 140 mmHg, DBP >
      or = 90 mmHg) and hence a high total risk of cardiovascular disease (CVD), only
      increasing age was associated with ACR in men and increasing SBP and pulse
      pressure in women. Smoking, elevated lipid and glucose levels were strongly
      associated with MA in individuals with a high total risk of CVD than in
      individuals with a low total risk. CONCLUSION: MA was associated with increasing
      blood pressure in both genders, age and CHD in men. Other cardiovascular risk
      factors/markers might be more influential in predicting ACR variation in
      nondiabetic/nonhypertensive individuals with a high total risk of CVD than in
      individuals with a low total risk.

PMID- 12190894
TI  - Evidence supporting the role of vitamin D in reducing the risk of cancer.

PMID- 12190893
TI  - Invasive pulmonary aspergillosis resulting in respiratory failure during
      neutrophil recovery from postchemotherapy neutropenia in three patients with
      acute leukaemia.
AB  - Respiratory failure is a severe complication of invasive pulmonary aspergillosis
      (IPA). Its pathogenesis is not well understood. We herein describe three cases of
      subacute respiratory failure that occurred during the recovery phase of
      neutropenia following induction chemotherapy for acute leukaemia with IPA. In
      each case, severe neutropenia (19-85 days), high-grade fever, severe anaemia, the
      use of granulocyte-colony-stimulating factor and increasing infusion volume were
      noted. As the neutrophil count was recovering, the shadows on the chest X-ray
      expanded with progressing hypoxia. We should pay attention to the respiratory
      failure during the recovery phase of neutropenia in patients with IPA.

PMID- 12190896
TI  - The ferrule effect: a literature review.
AB  - LITERATURE REVIEW: A ferrule is a metal ring or cap used to strengthen the end of
      a stick or tube. It has been proposed that the use of a ferrule as part of the
      core or artificial crown may be of benefit in reinforcing root-filled teeth. A
      review of the literature investigating this effect is presented. The literature
      demonstrates that a ferrule effect occurs owing to the artificial crown bracing
      against the dentine extending coronal to the crown margin. Overall, it can be
      concluded that a ferrule is desirable, but should not be provided at the expense
      of the remaining tooth/root structure.

PMID- 12190897
TI  - Effects of rotary instruments and ultrasonic irrigation on debris and smear layer
      scores: a scanning electron microscopic study.
AB  - AIM: This study evaluated debris and smear layer scores after two types of
      instruments manufactured from different alloys were used to ultrasonically
      activate irrigants during canal preparation. The influence of two rotary
      preparation techniques on cleanliness of the shaped canals was also studied.
      METHODOLOGY: Apical stops were prepared to size 45 in 42 single-canalled
      extracted premolars and canines, which were divided into six equal groups. Groups
      1, 2 and 3 were prepared by ProFile.04 (PF) while groups 4, 5 and 6 were prepared
      by Lightspeed (LS). All groups were irrigated using 5.25% NaOCl and 17% EDTA.
      Irrigants in groups 2 and 5 were ultrasonically activated using a size 15 steel K
      file and by a blunt flexible nickel-titanium wire in groups 3 and 6. Groups 1 and
      4 served as negative controls. Roots were split and canal walls examined at 15x,
      200x and 400x magnification in an SEM. Smear layer and debris scores were
      recorded at 3, 6 and 9 mm levels using a 5-step scoring scale and a 200- micro m
      grid. Means were tested for significance using nonparametric Mann-Whitney U and
      Kruskal-Wallis tests. RESULTS: Debris and smear layer scores for the six groups
      varied from 1.98 +/- 1.04 to 3.47 +/- 0.97 and from 1.37 +/- 0.4 to 2.36 +/-
      0.99, respectively. Although all groups had significantly higher smear layer and
      debris scores at the 3 mm levels compared to the 9 mm levels (P < 0.05), no
      significant differences were recorded due to the ultrasonic energy transmitted by
      the two alloys. CONCLUSION: Ultrasonically activated irrigants did not reduce
      debris or smear layer scores. This finding was not influenced by the material nor
      by the design of the instrument used to transmit ultrasonic activation.

PMID- 12190899
TI  - A study on the thickness of radicular dentine and cementum in anterior and
      premolar teeth.
AB  - AIM: This study aimed to measure the thickness of radicular dentine and cementum
      in incisors, canines and premolars, and to develop geometric average models.
      METHODOLOGY: The roots of 220 extracted human teeth were sectioned in three
      horizontal parallel planes and measured using an optical microscope. For each cut
      surface buccal, lingual, mesial, and distal thickness of the root wall was
      measured. Mean values of the thickness at each location of each cut surface were
      calculated. The observed differences in thickness by tooth type, location, and
      section were compared by ANOVA and Student's t-test. RESULTS: Maxillary central
      incisors and maxillary canines had the greatest widths. In all teeth with a
      single root, the wall thickness were greater on the lingual side than the buccal
      side. Although differences between mesial and distal thicknesses were not
      statistically significant. CONCLUSIONS: Wall thickness varied greatly. The
      lingual surfaces of roots were larger. All roots had thin walls in the apical
      third.

PMID- 12190898
TI  - In vivo determination of root canal length: a preliminary report using the Tri
      Auto ZX apex-locating handpiece.
AB  - AIM: The aim of this study was to assess the clinical perfomance of a cordless
      handpiece with a built-in apex locator - the Tri Auto ZX - designed for root
      canal preparation with nickel-titanium rotary files. METHODOLOGY: Twenty-five
      human maxillary incisor and canine teeth scheduled for extraction with mature
      apices were selected for the study. Informed written consent was obtained from
      each patient before treatment. After administration of local anaesthesia, the
      teeth were isolated and the pulp cavities accessed. The Tri Auto ZX along with a
      size 15 K-file was used in its electronic apex locating function based on the
      manufacturer's recommendations. A periapical radiograph with the file at the
      electronically determined constriction was taken, the file removed and the
      measurement registered as the electronic length (EL). To test the auto reverse
      function, a size 20 ProFile.04 taper NiTi rotary instrument was mounted in the
      handpiece. The point for the auto apical reverse function was preset on the panel
      at the 0.5 mm level. After the file was introduced into the canal and reached the
      predetermined level, the file automatically stopped and rotated in the opposite
      direction. A reference point was marked and this measurement was registered as
      the auto reverse length (ARL). All measurements were made twice by two different
      investigators. Teeth were then extracted and immersed in a 20% formalin solution
      for 48 h. After fixation, a size 15 file was inserted into the canal to measure
      the actual root canal length from the same reference point obtained with the Tri
      Auto ZX to the apical foramen, as seen in the stereo microscope. When the file
      tip was visible at the anatomical end of the canal it was withdrawn 0.5 mm and
      this measurement was registered as the actual length (AL). All measurements were
      expressed in mm and the measuring accuracy was set to 0.5 mm. The significance of
      the mean differences between EL and ARL and between EL and AL measurements at the
      5% confidence level was evaluated. RESULTS: EL measurements were coincident to
      ARL in all instances. EL and ARL were coincident to AL in 10 (40%) canals, in the
      remaining 15 canals (60%) the AL measurements were longer than EL and ARL (+0.5
      mm) in 14 instances and shorter (-0.5 mm) in one case. Overall, the AL was longer
      than the EL or ARL, the mean difference being -0.23 mm +/- 0.32 (P < 0.05).
      CONCLUSIONS: It was concluded that the Tri Auto ZX was useful and reliable. The
      Tri Auto ZX measurements protected against overpreparation.

PMID- 12190900
TI  - Shaping ability of GTTM Rotary Files in simulated resin root canals.
AB  - AIM: The aim of this study was to determine the shaping ability of GT Rotary
      Files in simulated root canals. METHODOLOGY: Forty canals with four different
      shapes in terms of angle (40 degrees and 60 degrees) and position of curvature
      (straight section before curve: 8 and 12 mm) were prepared using a crown
      down/stepback technique. Pre-operative and post-operative pictures, recorded
      using an image analysis system, were super-imposed and aberrations recorded.
      Measurements were carried out at 5 different points: at the canal orifice (0):
      half-way to the orifice in the straight section (HO); the beginning of the curve
      (BC); the apex of the curve (AC): the endpoint (EP). RESULTS: Two instrument
      fractures occurred and 9 instruments were deformed. Overall, eight zips and one
      ledge were created. There were significant differences (P < 0.001) for the total
      width of the canals between the various canal shapes at AC, BC and HO. There were
      significant differences (P < 0.001) for the amount of resin removed from the
      outer aspect of the curve at AC, BC and HO; and for the amount of resin removed
      from the inner aspect of the curve at all five measuring points (0, AC and EP (P
      < 0.05) and HO and BC (P < 0.001)). Mean transportation was towards the inner
      aspect of the canal in canals with straight sections of 12 mm regardless the
      curve angle; towards the outer aspect in canals with straight sections of 8 mm
      and 40 degrees curves at all the five measuring points, and at AC, BC and HO when
      the curve was 60 degrees. CONCLUSIONS: Under the conditions of this study, GT
      Rotary Files produced acceptable canal shapes. In narrow and curved canals, the
      length of the straight section of the canal determines the direction of
      transportation more than the angle of the curve. In the 60 degrees curves, a high
      incidence of instrument deformation was found when using the 0.04 tapered
      instruments.

PMID- 12190901
TI  - Image processing for enhanced observer agreement in the evaluation of periapical
      bone changes.
AB  - AIM: The aim of the present study was to evaluate the effect of root canal
      treatment on periapical lesions by conventional and subtracted digital
      radiographic images of clinical cases. METHODOLOGY: Eleven patients who exhibited
      clinical or radiological signs of periapical pathology received root canal
      treatment. Periapical radiographs were obtained immediately postoperatively and
      recall radiographs at intervals of 3, 6, 9 and 12 months postoperatively were
      obtained. Identical exposure geometry was maintained. From the standardized
      radiographs digitized images were produced. Four experienced practitioners
      interpreted the radiographs and the digitized images. They assessed 59 pairs of
      images projected at random using a slide projector. On the left side, there was a
      reference image with no lesion, and on the right an image either with or without
      a lesion. Each reader was asked to rate each pair of images on a three-point
      scale: yes, absolutely sure that gain or loss was present; uncertain, if there
      was gain or loss; no, absolutely sure that no gain or loss was present. There was
      no time limit for each decision. Inter- and intra-examiner agreement was analyzed
      using the kappa-statistic for the diagnosis of periapical bone density changes in
      the periapical region at the different time points either in conventional pairs
      of radiographs or using digital subtraction images. RESULTS: The inter-examiner
      agreement (P < 0.001) and the intra-examiner agreement (P = 0.02) when digital
      pictures where evaluated were significantly higher than with conventional
      radiographs. CONCLUSIONS: A highly significantly better observer agreement was
      achieved by digital subtraction radiography during the evaluation of the outcome
      of root canal treatment on periapical lesions.

PMID- 12190902
TI  - Influence of calcium hydroxide intracanal medication on apical seal.
AB  - AIM: The aim of this study was to determine the influence of calcium hydroxide
      intracanal medication and various techniques for its removal on the sealing
      ability of gutta-percha root fillings with a zinc oxide-eugenol sealer.
      METHODOLOGY: Eighty extracted mature human mandibular molar roots were divided
      into three groups of similar root-canal configuration. Calcium hydroxide paste
      was made by mixing calcium hydroxide powder with distilled water at a powder to
      liquid ratio of 1:1.25. After root canals were prepared and enlarged to a minimum
      of size 30 with the Profile 0.06 system, calcium hydroxide paste was placed in
      the canals of two groups, but no medication was placed in the control group. The
      intracanal calcium hydroxide was removed with two different techniques, 1 week
      after medication: K-files one size larger than the master apical file (MAF) were
      used with 2.5% NaOCl and 15% EDTA solutions in one group, whilst K-files the same
      size as the MAF were used with 2.5% NaOCl solution in another group. Canals were
      obturated with gutta-percha and Tubli-Seal cement using the lateral condensation
      technique. The apical sealing-ability was assessed by dye leakage and cross
      sections of the specimens were examined under a stereomicroscope. The dye
      penetration level was measured and analyzed using Fisher's exact test and
      Duncan's multiple range test. RESULTS: The calcium hydroxide-medicated groups
      showed significantly more dye leakage than the non-medicated control group (P <
      0.05). However, there was no significant difference between the two calcium
      hydroxide-medicated groups (P > 0.05). The stereomicroscopic views showed a
      relatively uneven and thicker layer of sealer in the calcium hydroxide-medicated
      groups. CONCLUSION: Calcium hydroxide intracanal medication may increase apical
      leakage of gutta-percha root fillings when a zinc oxide-eugenol sealer is used.

PMID- 12190903
TI  - Pulpal anaesthesia for mandibular central incisor teeth: a comparison of
      infiltration and intraligamentary injections.
AB  - AIM: This study compared the anaesthetic efficacy of infiltration and
      intraligamentary injections in the permanent mandibular central incisor.
      METHODOLOGY: Twelve healthy volunteers received each of the following methods of
      anaesthesia for one of their mandibular central incisors over four visits. 1
      Labial infiltration of 1.0 mL. 2 Lingual infiltration of 1.0 mL. 3 Labial
      infiltration of 0.5 mL plus lingual infiltration of 0.5 mL. 4 Intraligamentary
      injection of (118 mL. Two percent lidocaine with 1: 80 000 adrenaline and 30
      gauge needles were used throughout. Electrical pulp testing was performed before
      injection and every 2 min up to 30 min after the injection. Injection discomfort
      was recorded on a 100-mm visual analogue scale. Data were compared with ANOVA,
      Student's t-test and chi2 tests. RESULTS: Anaesthesia varied between techniques(F
      = 9.3, P < 0.001). The incidence of anaesthesia at any time was as follows: 50%
      success for labial infiltration; 50% success for lingual infiltration: 92%
      success for combined labial and lingual infiltration; 0% success for
      intraligamentary injections (chi2 = 20; P < 0.001). The mean (+/-SD) VAS score
      for intraligamentary injection discomfort was 28 +/- 12 mm, for buccal
      infiltrations 17 +/- 8 mm and for lingual infiltrations 16 +16 mm.
      Intraligamentary injections were more uncomfortable than buccal (t = 3.7: P <
      0.01) and lingual infiltrations (t = 2.67: P < 0.05). CONCLUSIONS: The most
      reliable method of the techniques investigated for obtaining pulpal anaesthesia
      in mandibular permanent central incisors was a combination of labial and lingual
      infiltration. Intraligamentary injections were unreliable and were more
      uncomfortable than infiltrations in the mandibular central incisor region.

PMID- 12190905
TI  - Incomplete tooth fracture following root-canal treatment: a case report.
AB  - AIM: To demonstrate the need for proper restoration of root-filled teeth.
      SUMMARY: Tooth fracture can be a sequel to root-canal treatment. It is associated
      with the removal of excessive amounts of the tooth substance during the
      instrumentation phase, the use of unnecessary force during obturation, or
      inadequate planning of the design of the eventual coronal restoration to include
      appropriate cuspal protection. Rarely, a fracture may be present in a tooth
      before treatment commences, but remains undetected. A case describing incomplete
      vertical tooth fracture of a root-filled mandibular first molar is presented.

PMID- 12190904
TI  - Comparison between a conventional technique and two bone regeneration techniques
      in periradicular surgery.
AB  - AIM: The aim was to demonstrate the efficacy of two materials for bone
      regeneration during periradicular surgery and their effects on the healing of
      periapical tissues. METHODOLOGY: Twenty-eight patients (30 surgical sites) were
      selected and distributed into three groups:group A, conventional technique; group
      B, conventional technique plus nonbioabsorbable GoreTex R Augmentation membrane;
      and group C, conventional technique plus the same membrane placed over a
      synthetic bioactive resorbable graft of a hydroxylapatite (OsteoGen) product in
      the bony defect. Clinical and radiological evaluations were completed immediately
      prior to surgery, a week later and every 3 months after surgery up to 12 months.
      Two histological evaluations were performed (at the beginning and at 12 months).
      RESULTS: The results showed complete clinical and radiographic healing (eight
      cases) for group C, with histologic evidence of trabecular bone in all cases. For
      group B, six out of nine cases showed complete radiographic healing, incomplete
      in one case and uncertain in two cases, with histologic evidence of trabecular
      bone in five out of eight cases, scar tissue in one case and granuloma in two
      cases. For group A, there was complete radiographic healing in four out of nine
      cases, incomplete in four and unsuccessful in one case, with evidence of
      granuloma in four out of eight, scar tissue in two cases and trabecular bone in
      two cases. CONCLUSIONS: It was concluded that the conventional technique was less
      predictable in its healing response during the 12 months of this study. The use
      of bone regeneration materials, such as nonbioabsorbablemembranes and resorbable
      hydroxylapatite improved the predictability of clinical, radiographic and
      histological healing.

PMID- 12190906
TI  - C-shaped root canals in mandibular second molars in a Saudi Arabian population.
AB  - AIM: The aim of this study was to determine the frequency of C-shaped canals in
      mandibular second molars in a population in Saudi Arabia and to establish a
      classification for the most common configurations. METHODOLOGY: One hundred and
      fifty-one mandibular second molars scheduled for root-canal treatment were
      examined over a 1-year period. The C-shaped canals were detected by radiographic
      and clinical examination. Teeth with C-shaped canal systems were categorized by
      using a modification of the classification of Melton. RESULTS: Of the 151 molars,
      16 (10.6%) exhibited C-shaped canals. Five molars were classified as category I,
      and three were considered category II. The remaining eight cases were classified
      as category III, with two in subdivision I, two in subdivision II, and the
      remaining four in subdivision IIL. CONCLUSIONS: The C-shaped canals in mandibular
      second molars vary considerably in their anatomical configuration with the result
      that debridement, obturation, and restoration may be difficult.

PMID- 12190907
TI  - Efficiency of rotary nickel-titanium FlexMaster instruments compared with
      stainless steel hand K-Flexofile--Part 1. Shaping ability in simulated curved
      canals.
AB  - AIM: The purpose of this study was to compare the shaping ability of FlexMaster
      rotary nickel-titanium instruments with stainless steel hand K-Flexofiles. This
      part of the two-part report describes the efficiency of these two instruments in
      simulated curved root canals. METHODOLOGY: Simulated 28 degree- and 35 degree
      curved canals were prepared by the FlexMaster instruments with a rotational speed
      of 250 rpm using a crown-down preparation technique. and by the K-Flexofiles
      using a reaming motion (n = 24 canals in each case). All canals were prepared up
      to size 35. The pre- and post-instrumentation images were recorded and assessment
      of the canal shape was completed with a computer image analysis program. The
      material removal was measured at 20 measuring points, beginning 1 mm away from
      the apex. Incidence of canal aberrations, preparation time,changes of working
      length and instrument failures were also recorded. RESULTS: In comparison with
      stainless steel K-Flexofiles, the rotary FlexMaster instruments achieved bet-ter
      canal geometry, showed less canal transportation and created fewer canal
      aberrations in both the canal types. Two FlexMaster instruments were separated,
      and 15 FlexMaster instruments and 11 K-Flexofiles were permanently deformed
      during preparation. However, these differences were not significant (P > 0.05).
      Between both the canal types, FlexMaster was significantly faster (P < 0.001)
      than K-Flexofiles. Both instruments maintained a good working distance.
      CONCLUSIONS: FlexMaster instruments prepared curved canals rapidly, and with
      minimal transportation towards the outer aspect of the curve.

PMID- 12190908
TI  - Efficiency of rotary nickel-titanium FlexMaster instruments compared with
      stainless steel hand K-Flexofile--Part 2. Cleaning effectiveness and
      instrumentation results in severely curved root canals of extracted teeth.
AB  - AIM: To determine the cleaning effectiveness and the shaping ability of
      FlexMaster nickel-titanium rotary instruments and stainless steel hand K
      Flexofiles during the preparation of curved root canals in extracted human teeth.
      METHODOLOGY: A total of 48 root canals with curvatures ranging between 25 degrees
      and 35 degrees were divided into two groups of 24 canals. Based on radiographs
      taken prior to the instrumentation with the initial instrument inserted into the
      canal, the groups were balanced with respect to the angle and the radius of canal
      curvature. Canals were prepared by FlexMaster instruments using a crown-down
      preparation technique or by K-Flexofiles using a reaming working motion up to
      size 35. After each instrument, the root canals were flushed with 5 mL of a 2.5%
      NaOCl solution and at the end of instrumentation with 5 mL of NaCl. Using the pre
      and post-instrumentation radiographs, straightening of the canal curvatures was
      determined with a computer image analysis program. After splitting the roots
      longitudinally, the amount of debris and smear layer were quantified on the basis
      of a numerical evaluation scale, using a scanning electron microscope. RESULTS:
      Completely cleaned root canals were not found with any of the two instruments. In
      general, K-Flexofiles resulted in significantly less debris(P < 0.001) and less
      smear layer (P < 0.05) than Flex-Master instruments, but these differences were
      not significant in the apical third of the canals (P > 0.05). FlexMaster
      instruments maintained the original canal curvature significantly better (P <
      0.0001) than K-Flexofiles. No significant differences were detected between the
      instruments (P > 0.05) for the time taken to prepare the canals. CONCLUSIONS:
      Under the conditions of this study, K-Flexofiles allowed significantly better
      canal cleaning than FlexMaster instruments. FlexMaster instruments maintained the
      original curvature significantly better.

PMID- 12190909
TI  - A laboratory study of the effect of calcium hydroxide mixed with iodine or
      electrophoretically activated copper on bacterial viability in dentinal tubules.
AB  - AIM: The aim of this laboratory study was to evaluate the ability of calcium
      hydroxide (CH), CH/iodine-potassium iodide (IKI) and electrophoretically
      activated copper to kill bacteria in dentinal tubules. METHODOLOGY: In an in
      vitro model of dentinal tubule infection, 42 cylindrical root specimens, prepared
      from freshly extracted bovine teeth were used. After removal of the smear layer,
      intracanal dentinal tubules were infected with Enterococcus faecalis for 3 weeks.
      CH alone or preparations of CH with copper or IKI were placed in the root canal
      for 1 week. In specimens containing copper/CH, an electrophoretic current(5 mA/5
      min) was applied using two electrodes follow-ing placement of the medicament in
      the canal. Powder dentine samples obtained from the canal wall using ISO sizes:
      025, 027, 029, 031 and 033 burs were examined for the presence of viable bacteria
      by inoculating agar plates and counting colony forming units (cfu). RESULTS: A
      significant difference was found between the experimental groups and the positive
      control group. CH and CH/IKI significantly (P < 0.001)reduced bacterial viability
      in dentinal tubules to a depth of 200 microm. Specimens with CH/IKI had
      significantly fewer viable bacteria than CH alone in tubules between the depths
      of 200-500 microm. Treatment with CH/copper and electrophoresis was most
      effective: specimens showed no viable bacteria in dentinal tubules to a depth of
      500 microm from the root-canal space. CONCLUSIONS: IKI or electrophoretically
      activated copper additives can significantly improve the antibacterial properties
      of CH in dentinal tubules.

PMID- 12190910
TI  - A preliminary study of the percentage of gutta-percha-filled area in the apical
      canal filled with vertically compacted warm gutta-percha.
AB  - AIM: The aim of this study was to determine the influence of the width of apical
      root canals and the depth of heat application during warm vertical compaction on
      the percentage of gutta-percha-filled area (PGFA) in the apical root canal.
      METHODOLOGY: Two groups of extracted human canines (total 60) were instrumented
      and filled with vertically compacted warm gutta-percha up to the apical foramen
      (AF). Using the Touch 'n Heat device heat was applied 4 mm from the AP in one
      group and 2 mm in the other. The number of teeth with gutta-percha extrusion was
      recorded. A horizontal section was cut 1.5 mm from the AF of each tooth. The
      cross-sectional area of the canal and the gutta-percha was measured using an
      image-analysis programme. The PGFA was then calculated. Multiple linear
      regression was performed to investigate the association between the experimental
      variables and the PGFA, and the occurrence of gutta-percha extrusion. RESULTS: A
      significant association was seen between the depth of heat application and the
      PGFA (P= 0.000), and between the canal area and the PGFA (P= 0.038). The average
      PGFA reached 96.1% when heated to 2 mm, as compared with 87.0% when heated to 4
      mm. PGFAs were lower in wide apical canals than in small canals. Gutta-percha
      extruded in seven teeth (12%) and was independent of experimental variables.
      CONCLUSIONS: After warm vertical compaction, the quality of adaptation of gutta
      percha to the wall of the apical root canal varies; the influencing factors in
      this study were the depth of heat application and the width of the apical root
      canal.

PMID- 12190911
TI  - Failure of ProFile Ni-Ti instruments used by an inexperienced operator under
      access limitations.
AB  - AIM: The purpose of this study was to evaluate the failure incidence of ProFile
      nickel-titanium rotary instruments (PRI) when used by an inexperienced operator
      in conjunction with different motors and under limitations of access.
      METHODOLOGY: PRI with 0.06 taper were used by an inexperienced operator in a
      crown-down technique. The teeth were mounted in resin arches of a phantom head to
      reproduce limitations of access. In groups 1-4, air, high torque control, low
      torque control and very low torque control motors were used, respectively. Each
      group included 30 canals in extracted human molars. One set of PRI sizes 40-15
      was used for each canal; the PRI were sterilized before each case. A 2.5% NaOCl
      solution was used as an irrigant. An inexperienced operator performed all the
      cleaning and shaping procedures after application of a rubber dam. The opening of
      the mouth in the phantom head was standardized for the four groups. The number of
      deformed and separated instruments was recorded for the various experimental
      groups and analyzed statistically for significance with chi-square tests.
      RESULTS: A high incidence of instrument deformation and separation occurred with
      the air, high torque control and low torque control motors. Only seven and two
      instruments deformed and separated, respectively, with the very low torque
      control motor, whereas at least 23 and 10 instruments deformed and separated
      respectively with the other motors. CONCLUSIONS: A very low torque control motor
      was safer than on air, high torque control or low torque control motors when PRI
      with 0.06 taper were used by an inexperienced operator in a crown-down manner at
      170 rpm.

PMID- 12190912
TI  - In vitro comparison of root-canal measurements with conventional and digital
      radiology.
AB  - AIM: The present study compared the efficacy of digital and conventional
      radiology for root-canal length measurement. METHODOLOGY: Seventy extracted teeth
      with pre-served roots were used. Root-canal length measurements were completed
      with K-Flexofiles (numbers 08, 10 and 15) with conventional and digital
      radiography using two systems (radiovisiography and photostimulate storage
      phosphor). All films and sensors were exposed at projections of 0 degrees and 20
      degrees to the mesial. The images obtained were evaluated with and without
      magnification, and analysed using the Cohen's kappa test. The accuracy of the
      three systems to determine the root-canal length were evaluated by measuring the
      distance from the tip of the file to the apex. RESULTS: Most of the values
      corresponding with the apex occurred with conventional radiology. The digital
      systems yielded negative values that improved with a size 15 file. The agreement
      between the two digital systems was the best with size 15 file using 0 degrees
      projection (66.7%). CONCLUSIONS: Conventional radiology remains the technique of
      choice in determining the root-canal length; the digital techniques yielded good
      results for size 15 file.

PMID- 12190913
TI  - The effect of AH 26 and AH Plus on MCF-7 breast cancer cell proliferation in
      vitro.
AB  - AIM: The purpose of this study was to determine whether AH 26 and AH Plus have in
      vitro oestrogenic effects. METHODOLOGY: MCF-7 breast cancer cells were
      trypsinized and plated in 24-well plates at initial concentrations of 10,000
      cells per well in 5% FBS in DME. Cells were allowed to attach for 24 h; then the
      seeding medium was replaced with 10% CDHuS-supplemented phenol red-free DME.
      Different concentrations of the test compound were added to sample wells (AH 26
      and AH Plus at 1/100 to 1/1,000,000 dilutions), 10 pM estradiol-17beta to
      positive controL and no sub-stance to negative control (hormone-free control
      cells). The assay was stopped after 144 h. RESULTS: AH 26-powder induced MCF-7
      cell proliferation in a dose-dependent manner. The cell yield obtained with AH 26
      powder at 1/100 dilution sample was 2.5-fold greater than in control cultures.
      The sam-ple prepared with mixed AH 26 paste/powder 1:1 also induced MCF-7 cell
      proliferation, but showed less potency than AH 26-powder alone. The cell yield
      obtained with AH 26 paste/powder at 1/100 dilution sample was 1.9-fold greater
      than in control cultures. AH Plus did not show in vitro oestrogenic effect.
      CONCLUSIONS: AH 26 showed in vitro oestrogenic effect, but not AH Plus. The
      endodontist must consider the possible oestrogenic effect of AH 26, as well as
      the cytotoxic effects of root filling materials, and avoid the leakage of sealer
      through the apex during root canal treatment.

PMID- 12190914
TI  - Hemisection for treatment of an advanced endodontic-periodontal lesion: a case
      report.
AB  - AIM: To emphasize the importance of primary endodontic treatment when dealing
      with endo-perio lesions and to demonstrate the considerable healing potential of
      the endodontic aspect. CASE REPORT: After several years of unsuccessful
      symptomatic periodontal treatment, an advanced endo-perio lesion on a right
      mandibular first molar was successfully treated by root-canal treatment and
      hemisection after the re-evaluation of the lesion. This successful treatment
      appeared to have a positive effect on the patient's general well-being. KEY
      LEARNING POINTS: The origin of a combined endo-perio lesion is indicated by its
      clinical and radiographic appearance. The periodontal situation is often
      misinterpreted. The prognosis for the endodontic element of treatment is
      excellent. Local pathologic processes in the oral cavity may affect a patient's
      general health.

PMID- 12190917
TI  - The discovery of thymus function and of thymus-derived lymphocytes.
AB  - For centuries the thymus remained an enigmatic organ with unknown functions. The
      first demonstration of its crucial role in establishing the development of a
      normal immune system was provided in 1961, when it was shown that mice
      thymectomized immediately after birth had poorly developed lymphoid tissues,
      impaired immune responses and inordinate susceptibility to intercurrent
      infections. Although thymus lymphocytes were believed to be immunoincompetent, it
      was shown in 1967 that they could respond to antigen by proliferating and giving
      rise to a progeny of cells that could not produce antibody, but enabled other
      lymphocytes, derived from bone marrow, to differentiate to antibody-forming
      cells. This was the first unequivocal demonstration, in mammalian species, of the
      existence of two major interacting subsets of lymphocytes, T and B cells. It
      required a re-evaluation of many immunological phenomena, such as tolerance,
      memory and autoimmunity, and it was followed by an avalanche of work elucidating
      many of the mysteries of the immune system.

PMID- 12190918
TI  - One cell, one antibody: prelude and aftermath.
AB  - This essay seeks to summarize one scientist's pilgrim's progress through the
      world of antibody formation, attempting to capture the flavor of problems as
      encountered within their times. It seeks to portray a world where the direct
      template hypothesis ruled the day, where the function of lymphocytes was unknown,
      let alone the difference between T and B cells, and where antibody genes were but
      a dream. Struggles to establish the credentials of the clonal selection
      hypothesis are presented in some detail, as are the implications which followed
      the 'one cell - one antibody' discovery. The other two main preoccupations of the
      author are presented more briefly, namely the essential features of the germinal
      center and the cellular basis of immunological tolerance within the B lymphocyte
      compartment. Naturally, the experiments become more sophisticated as both
      knowledge and technology mature. A continuing thread within the unfolding story
      is that one must not shy away from developing new techniques when problems demand
      them.

PMID- 12190919
TI  - The immune system: a weapon of mass destruction invented by evolution to even the
      odds during the war of the DNAs.
AB  - Living systems operate under interactive selective pressures. Populations have
      the ability to anticipate the future by generating a repertoire of elements that
      cope with new selective pressures. If the repertoire of such elements were
      transcendental, natural selection could not operate because any one of them would
      be too rare. This is the problem that vertebrates faced in order to deal with a
      vast number of pathogens. The solution was to invent an immune system that
      underwent somatic evolution. This required a random repertoire that was generated
      somatically and divided the antigenic universe into combinatorials of
      determinants. As a result, it became virtually impossible for pathogens to escape
      recognition but the functioning of such a repertoire required two new regulatory
      mechanisms: 1) a somatic discriminator between Not-To-Be-Ridded ('Self') and To
      Be-Ridded ('Non-self') antigens, and 2) a way to optimize the magnitude and
      choice of the class of the effector response. The principles governing this dual
      regulation are analyzed in the light of natural selection.

PMID- 12190920
TI  - The pas de deux of viruses and CD8 T cells.
AB  - The vertebrate immune system has evolved to deal with parasitic life forms, so it
      is hardly surprising that experiments with pathogens have proved illuminating for
      immunology. Those of us who have worked for years with infectious processes are
      acutely conscious that we do little more than probe the vast 'experiment of
      nature.' There is no place for doctrinaire rigidity in this extraordinarily
      complex area of biology. Though we have obviously tried to do rational
      experiments, much of the novelty that has been brought in to immunology from the
      analysis of the virus-specific host response has, in a very real sense, been the
      product of what we now call 'discovery science'. The following relates some of
      the research that I was involved in personally and attempts to put it in the
      context of both the history of the field and the events of the time. Virus
      infections, particularly HIV, pose enormous challenges for the future. It is
      generally helpful to know a little of what went before.

PMID- 12190921
TI  - Instructive selection and immunological theory.
AB  - The turning point of modern immunological theory was the advent of the clonal
      selection theory (Burnet, Talmage - 1957). A useful heuristic in the
      classification of theoretical models was the contrast of 'instructive' with
      'selective' models of the acquisition of information by biological systems. The
      neo-Darwinian synthesis of the 1940s had consolidated biologists' model of
      evolution based on prior random variation and natural selection, viz.
      differential fecundity. While evolution in the large was by then pretty well
      settled, controversy remained about examples of cellular adaptation to chemical
      challenges, like induced drug-resistance, enzyme formation and the antibody
      response. While instructive theories have been on the decline, some clear cut
      examples can be found of molecular imprinting in the abiotic world, leading, e.g.
      to the production of specific sorbents. Template-driven assembly, as in DNA
      synthesis, has remained a paradigm of instructive specification. Nevertheless,
      the classification may break down with more microscopic scrutiny of the processes
      of molecular fit of substrates with enzymes, of monomers to an elongating polymer
      chain, as the reactants often traverse a state space from with activated
      components are appropriately selected. The same process may be 'instructive' from
      a holistic, 'selective' from an atomic perspective.

PMID- 12190922
TI  - Travels along the viral-immunobiology highway.
AB  - Michael Oldstone began his biomedical research career over three decades ago,
      showing contrary to established scientific dogma, the host was not tolerant but
      made a specific antiviral immune response during persistent virus infections.
      Further, the immune response to the virus actually caused tissue damage and
      disease, the first observation that several manifestations ordinarily
      accompanying infections were due to the host's antiviral immune response. These
      observations made originally with lymphocytic choriomeningitis virus (LCMV) and
      murine retroviruses were extended to other microbial infections including those
      in humans. Buildings on this work, he showed that antibodies to virus could
      recognize similar amino acid sequences or motifs found in host/cell proteins and
      cause disease. This cross-reactivity, referred to as molecular mimicry, has and
      is now been extensively studied by many laboratories. Another mechanism by which
      persistent virus infection produced disease was uncovered by cocumenting that
      viruses could alter the differentiation or "luxury" function of cells with
      causing cell destruction, thereby altering homeostasis. Finally, Oldstone was one
      of the first to show that viruses caused immunosuppression, abrogated immunologic
      surveillance resulting in viral persistence, work carried out long before HIV was
      discovered. He has also defined host-cell receptors for several viruses. In
      recent studies, host-cell receptor used by LCMV strains or variants that cause
      persistence have been identified. This led to observations that a single amino
      acid on the viral glycoprotein provides the infectious agent a selective ability
      ot displace extra-cellular matrix molecule, bind to and infect dendritic cells
      leading to their inability to act as antigen presenting cells thereby aborting
      the host's ability to generate the antiviral immune response required to clean
      the infection.

PMID- 12190924
TI  - The discovery of linkage between the MHC and genetic control of the immune
      response.
AB  - Immunization of rabbits, and inbred strains of mice with branched, multichain,
      synthetic polypeptides, such as (T, G) - A--L and (H, G) - A--L, revealed
      striking differences in the ability of different strains of mice to produce
      specific antibody. F1 and F1 x parental backcross mice revealed clear genetic
      control. Initial attempts to link this genetic control to known genetic markers
      were unsuccessful. The second approach, which attempted to transfer response from
      high or immediate responders into low responder recipients, initially encountered
      graft vs. host and host vs. graft reactions. The transfer of F1 spleen cells into
      the low responder parent demonstrated that ability to respond was a property of
      immunocompetent cells (spleen cells), not of the recipient's background genes.
      Mapping studies with recombinant H2 haplotype congenic strains, and a classic 4
      point mapping cross were concordant in placing the gene controlling this trait
      within the H2 complex, between the K and Ss loci. Subsequent studies mapped the
      genes for stimulation in the mixed lymphocyte culture reaction to the same
      position, suggesting cell surface expression. Production of antisera to 'I
      region' products defined 'Ia' antigens, the 2-chain alpha/beta MHC class II
      molecules.

PMID- 12190923
TI  - Human histocompatibility proteins.
AB  - Transplantation antigens (later called histocompatibility proteins) were named by
      Peter Gorer in the 1930s. After 4 decades of immunological work emphasizing their
      importance in immunobiology, structural work on these proteins began about 1970.
      During the first decade, HLA proteins were isolated and then separated into two
      groups. Biochemical studies established the close structural relationships of
      these groups (now called class I and class II MHC proteins). These structures
      both contained four domains, although the domains were linked differently. Two of
      these domains were immunoglobulin-like. They were the first proteins (aside from
      immunoglobulins) identified as members of the immunoglobulin superfamily of
      proteins. The crystallization of these proteins in the second decade led to
      elucidation of the structures of class I and class II MHC proteins, which has
      changed the way we think about immunology. These molecules each present peptides
      (8-9mers in the case of class I and 13-14mers in the case of class II) to
      initiate the immune response.

PMID- 12190925
TI  - Perspective on antigen processing and presentation.
AB  - The phenomenon of antigen processing and presentation and the concept that T
      cells recognize peptides resulting from the partial catabolism of proteins, are
      relatively new. These concepts were first recognized and developed at a time when
      lymphocyte immunity - the adaptive system - and cellular immunity, with its major
      component of activated macrophages, were not perceived as part of one integrated
      system. To me, it was the fundamental findings on the role of major
      histocompatibility (MHC) molecules that set the framework for understanding how
      phagocytes and the antigen presenting cell (APC) system interact with the
      adaptive cellular system, in a truly symbiotic relationship (1). In this chapter
      we make a historical review of the developments that, in my biased opinion, led
      to the understanding of antigen presentation as a central event. I emphasize my
      own work, placing it in my perspective of how I saw the field moving.

PMID- 12190926
TI  - Uncertainties - discrepancies in immunology.
AB  - The many immunological observations and results from in-vitro or in-vivo
      experiments vary, and their interpretations differ enormously. A major problem is
      that within a normal distribution of biological phenomena, which are measurable
      with many methods, virtually anything is possible. Within a coevolutionary
      context, the definition of biologically relevant thresholds is an important key
      to improve our understanding of weaknesses and strengths of the immune system.
      This review is a personal view, comparing textbook rules and experiments using
      model antigens with observations on immunity against infections or tumors to
      critically evaluate our perception and understanding of specificity, affinity
      maturation, antigen presentation, selection of the class of the immune response,
      immunological memory and protective immunity, positive selection of T cells and
      self/nonself discrimination.

PMID- 12190927
TI  - The thymus and negative selection.
AB  - Maintenance of tolerance to self antigens is presumed to reflect a combination of
      central and peripheral tolerance. For T cells, central tolerance occurs during
      early T cell development in the thymus and causes cells with strong reactivity to
      self antigens to be destroyed in situ (negative selection). Here, we summarize
      evidence that negative selection can occur in the thymic medulla and affects a
      population of semimature HSA+ T cells. The influence of costimulatory molecules,
      Fas and cytokines on negative selection is discussed.

PMID- 12190928
TI  - Cellular immunology in a historical perspective.
AB  - Bruton's XLA and DiGeorge syndrome patients show that two basic immune systems
      are distinct from each other in humans - thymus-dependent cell-mediated
      immunodeficiencies vs. antibody-based immunodeficiencies. The appendix-sacculus
      lymphoid organ of rabbits, like the bursa of Fabricius, represents a central
      lymphoid organ. Chronic granulomatous disease of childhood (CGD) revealed that
      phagocytosis killing of catalase-positive microorganisms employ oxidative burst.
      Bone marrow transplantation (BMT) proved life saving in severe combined
      immunodeficiency (SCID). The first BMT cured XSCID and the second BMT cured a
      complicating aplastic anemia launching BMT as a treatment of many diseases. Now
      75 fatal diseases have been cured by myeloablative BMT. BMT also cured
      experimental autoimmune diseases. BMT alone did not cure lupus with polyarthritis
      in MRL/lpr mice or polyarthritis in NZB/KN mice, but BMT plus bone (stromal cell)
      transplants cured these diseases. Autoimmune diseases and lethal
      glomerulonephritis were prevented or cured in BXSB mice by mixed allogeneic plus
      syngeneic BMT. X-linked Hyper IgM syndrome (XHIM) was also cured by BMT from a 2
      year-old MHC-matched sibling donor. Nonmyeloablative BMT plus mesenchymal stem
      cells (stromal cells) was effective treatment for a form of collagen-vascular
      disease and also a lethal form of hypophosphatasia. Mannan-binding lectin, an
      opsonin that activates the complement system when mutated and at low levels in
      blood, opens a door to frequent infections throughout childhood and adult life.
      This new immunodeficiency is based on genetic mutations that involve a native
      defense system.

PMID- 12190929
TI  - The road ended up at stem cells.
AB  - For me the search for hematopoietic stem cells (HSC) actually started with the
      discovery by Till, McCulloch, and colleagues (1-3) that bone marrow contained
      single cells that could give rise to myeloerythroid colonies in the spleen, and
      sometimes these colonies contained cells that made more spleen colonies as well
      as radioprotected and reconstituted lethally irradiated mice (3). But in
      retrospect, it should have started with the remarkable observation of Ray Owen in
      1945 that bovine fraternal twins sharing a single placenta and blood circulation
      retained production of blood cells genetically defined to be from both throughout
      their life (4). It could be argued that this was the experiment that began both
      modern experimental hematology as well as modern cellular immunology. The Till,
      McCulloch, Wu, Becker, and Simonovitch experiments were elegant demonstrations
      that single, genetically marked cells existed (random DNA breaks and
      translocations induced by sublethal irradiation of the donor bone marrow) that
      could both self-renew and differentiate (2, 5). But these experiments did not put
      the pure cells in the hands of scientists, and so most of their functions for the
      next 25 years were implied rather than directly analyzed. Just as genetics is the
      complement to biochemistry (when one considers genes and gene products), cell
      marking is the complement to cell purification in the fields of developmental and
      cellular biology. The first attempts at such cellular purification came from the
      'school' of Till & McCulloch (6, 7), and independently the school of Van Bekkum
      in the Netherlands (8). But what was lacking in those experiments and at that
      time were both a comprehensive approach that would take into account the clonal
      activity of stem cells in both self-renewal and differentiation to all blood cell
      outcomes, and the tools with which one could separate what turned out to be an
      extremely rare population in the bone marrow. And, it wasn't known until much
      later that most day 8-10 spleen colonies were the progeny of progenitors, not
      stem cells (9). Two inventions facilitated the technology of purification of HSC:
      the advent of monoclonal antibody technology by Kohler & Milstein (10), and the
      development of the multiparameter fluorescence activated cell sorter by the
      Herzenberg group (11). My laboratory had established assays for the clonal
      precursors of T cells and B cells, and we had been using the Till-McCulloch
      spleen colony clonal assays since the mid-1960s. In the late 1970s and early
      1980s we began in earnest the search for mouse early hematopoietic progenitors,
      including HSCs (12-16). The purification of HSCs proved to be much like the
      purification of an enzyme, or a cell surface receptor, or a gene. Successive
      enrichments finally led to the isolation of a population, which could no longer
      be subdivided and which contained precursors that read out in all clonal assays
      as well as in radioprotection of lethally irradiated hosts (17). Our first
      experiments transplanting single HSC in 1991 and 1992, led to the definitive
      demonstration that these were indeed HSCs (18-20). But these experiments and the
      ideas that led to them were developed in the context of immunology and
      experimental hematology as they were emerging in the 1950s and 60 s. This volume
      of Immunological Reviews is a rich testimony to the kinds of ideas and
      experiments that, at least in retrospect, turned out to be critical. Many roads
      were taken, but only one ended up at stem cells.

PMID- 12190930
TI  - Exploring lymphocyte differentiation pathways.
AB  - Highlights in a 4-decade exploration of lymphocyte differentiation begin with
      comparative studies in birds and mammals leading to recognition of the separate T
      and B-cell differentiation pathways and their cooperative interaction. The
      global effects of aborting IgM B-cell development with anti-mu antibodies
      indicated that B cells can undergo immunoglobulin isotype switching. A search for
      the mammalian bursa equivalent that began with an extended excursion through the
      gut-associated lymphoepithelial tissues ultimately led to the hematopoietic
      tissue origin of mammalian B cells. The identification of the precursors of B
      cells in hematopoietic tissues provided an expanded view of the life history of B
      cells. A recurring theme in this essay is the interplay between understanding
      normal lymphocyte differentiation and the defects that underlie immunodeficiency
      diseases and lymphoid malignancies.

PMID- 12190931
TI  - Molecular versatility of antibodies.
AB  - As immunology developed into a discrete discipline, the principal experimental
      efforts were directed towards uncovering the molecular basis of the specificity
      exhibited by antibodies and the mechanism by which antigens induced their
      production. Less attention was given to how antibodies carry out some of their
      effector functions, although this subject presents an interesting protein
      chemical and evolutionary problem; that is, how does a family of proteins that
      can bind a virtually infinite variety of ligands, many of which the species
      producing that protein has never encountered, reproducibly initiate an
      appropriate response? The experimental data persuasively suggested that
      aggregation of the antibody was a necessary and likely sufficient initiating
      event, but this only begged the question: how does aggregation induce a response?
      I used the IgE:mast cell system as a paradigm to investigate this subject. Data
      from our own group and from many others led to a molecular model that appears to
      explain how a cell 'senses' that antigen has reacted with the IgE. The model is
      directly applicable to one of the fundamental questions cited above, i.e. the
      mechanism by which antigens induce the production of antibodies. Although the
      model is conceptually simple, incorporating the actual molecular events into a
      quantitatively accurate scheme represents an enormous challenge.

PMID- 12190932
TI  - Primary immunodeficiency diseases: dissectors of the immune system.
AB  - The past 50 years have seen enormous progress in this field. An unknown concept
      until 1952, there are now more than 100 different primary immunodeficiency
      syndromes in the world's literature. Each novel syndrome has shed new insight
      into the workings of the immune system, dissecting its multiple parts into unique
      functioning components. This has been especially true over the past decade, as
      the molecular bases of approximately 40 of these diseases have been identified in
      rapid succession. Advances in the treatment of these diseases have also been
      impressive. Antibody replacement has been improved greatly by the development of
      human immunoglobulin preparations that can be safely administered by the
      intravenous route, and cytokine and humanized anticytokine therapies are now
      possible through recombinant technologies. The ability to achieve life-saving
      immune reconstitution of patients with lethal severe combined immunodeficiency by
      administering rigorously T-cell-depleted allogeneic related haploidentical bone
      marrow stem cells has extended this option to virtually all such infants, if
      diagnosed before untreatable infections develop. Finally, the past 3 years have
      witnessed the first truly successful gene therapy. The impressive results in X
      linked severe combined immunodeficiency offer hope that this approach can be
      extended to many more diseases in the future.

PMID- 12190933
TI  - Studies of normal and neoplastic lymphocytes.
AB  - This brief review encapsulates a nearly 50-year career in biomedical research,
      primarily studying human leukemias and lymphomas, but also involving normal
      lymphocytes. Early observations included the feasibility of bone marrow
      transplantation (and related problems with graft-vs.-host reactions); the
      mitogenic effect of phytohemagglutinin (and resultant human lymphocyte culture
      techniques); and early cytogenetic findings in human leukemias, both lymphocytic
      and myeloid (including the Philadelphia chromosome). Subsequent studies of normal
      human lymphocytes have contributed to our enormously expanding knowledge of their
      basic biology, especially regulatory pathways, both extracellular and
      intracellular. Further work with human lymphoid neoplasms has helped extend the
      early chromosomal findings to the specific genes involved, including several
      regulating apoptosis; and also contributed to the concept of clonal evolution as
      a basic underlying mechanism of tumorigenesis in general. This career has covered
      a period of remarkable growth of knowledge concerning both normal and neoplastic
      lymphocytes, with potential for many important future clinical applications; it
      has been a privilege to participate.

PMID- 12190934
TI  - Reprogramming the immune system.
AB  - The immune system is organized so as to react to pathogens without risking damage
      to self. Harnessing those processes that prevent self-reactivity will have
      enormous potential in clinical medicine. This review outlines the efforts of this
      laboratory over the last 25 years to exploit tolerance so as to reprogram the
      immune system for therapeutic purposes.

PMID- 12190935
TI  - Human retroviruses after 20 years: a perspective from the past and prospects for
      their future control.
AB  - Among viruses the human retroviruses may be of special interest to immunologists,
      because they target cells of the immune system, particularly mature CD4+ T cells,
      impair their function and cause them to grow abnormally (human T-cell leukemia
      virus, HTLV) or to die (human immunodeficiency virus, HIV). Human retroviruses
      cause disease ranging from neurological disorders and leukemias (HTLV-1) to AIDS
      (acquired immunodeficiency virus) (HIV) and promote development of several types
      of malignancies (HIV). They share many common features, but their contrasts are
      greater, especially the far greater replication and variation of HIV associated
      with its greater genomic complexity. Both have evolved striking redundancy for
      mechanisms which promote their survival. Thus, HTLV has redundant mechanisms for
      promoting growth of provirus containing T cells needed for virus continuity,
      because it is chiefly through its cellular DNA provirus that HTLV replicates and
      not through production of virions. Conversely, HIV has redundancy in its
      mechanisms for promoting virion replication and escape from the host immune
      system. It is via these redundant mechanisms that they produce disease: leukemias
      from mechanisms promoting T-cell proliferation (HTLV-1) and AIDS from mechanisms
      promoting virus replication and T-cell death (HIV). The practical challenges for
      the future are clear. For HTLV-1, education and control of breastfeeding. For
      HIV, the formidable tasks now ahead in part demand new kinds of talent, talents
      that will foster greater insights into the development of therapy for the
      developing countries, new forms of less toxic therapies for all infected persons,
      a continued and expanded commitment to education, and a persistent 'never say
      die' commitment to the development of a truly preventive vaccine with all the
      scientific and nonscientific challenges that these objectives face.

PMID- 12190936
TI  - Production of acute and chronic itch with histamine and contact sensitizers in
      the mouse and guinea pig.
AB  - Itch is a major symptom of skin disease and is poorly understood, in part due to
      the lack of adequate small animal models. We show, using iontophoresis of
      histamine and capsaicin, that it is possible to induce scratching behaviour in
      both guinea pig and mouse. Use of iontophoresis may obviate the problems of
      induction of pain as well as itch when injection is used. The behavioural
      response to capsaicin, however, differs from that seen with histamine, raising
      the possibility that the use of scratch counts as a method of measuring itch
      severity needs to be set in the context of other responses. Naloxone partly
      inhibits scratching in mouse and guinea pig due to histamine. We also show that
      contact sensitization with 2-4 dinitrochlorobenzene (DNCB) can be used as a
      simple assay for chronic itch allowing study of scratching over at least a 15-h
      period. The characteristics of scratching (but not the time course) induced with
      DNCB are similar to those seen with histamine.

PMID- 12190937
TI  - mRNA expression of tumor-associated antigens in melanoma tissues and cell lines.
AB  - Tumor-associated antigens (TAA) are increasingly used as specific targets for
      immune therapy of malignant melanoma. The aim of the present study was to provide
      a basis for selecting the most suitable TAA by analyzing the mRNA expression of a
      large panel of TAA by RT-PCR and Northern blotting. We have chosen primers
      differentiating four groups of TAA (MAGE-A, MAGE-B, and two groups of GAGE-genes)
      and 13 individual TAA (MAGE-A2 and -A3, RAGE-1, -2, -3, and -4, LAGE-1a and -1b,
      NY-ESO-1, GAGE-1, SSX-2, SCP-1, and cTAGE-1) based on most recent sequence data.
      In addition, the RAGE-gene family has been separated into its four members by a
      novel designed nested PCR, which was confirmed by Northern analysis. Furthermore,
      the chromosomal organization and relationship between the RAGE-family and MOK was
      analyzed. RAGE-4 mRNA could be shown for the first time to be present in testis
      tissue. The most frequently expressed TAA were the MAGE-A and the GAGE-3,-4,-5,
      6,-8 group, whereas among individual TAA MAGE-A2, -A3, RAGE-1, -3, and LAGE-1a/b
      were found within most specimens and are thus promising candidates for immune
      therapy. In comparison, melanoma metastatic specimens and cell lines show similar
      profiles of TAA expression, but individual TAA differ notably between both types
      of samples indicating that results from cell lines are not always applicable to
      tumor specimen.

PMID- 12190938
TI  - Effect of parathyroid hormone-related protein on fibroblast proliferation and
      collagen metabolism in human skin.
AB  - The parathyroid hormone-related protein (PTHrp), structurally similar to the
      parathyroid hormone (PTH) in its NH(2)-terminal part, was first identified as a
      tumour-derived peptide responsible for a paraneoplastic syndrome known as humoral
      hypercalcemia of malignancy. The PTHrp gene is expressed not only in cancer but
      also in normal tissues during adult and/or fetal life, where it plays
      predominantly paracrine and/or autocrine roles. In the skin PTHrp produced by
      keratinocytes acts on fibroblasts by complex cooperative circuits involving
      cytokines and growth factors. In this report, we studied the direct effects of
      synthetic PTHrp 1-40 on proliferation and collagen synthesis and matrix
      metalloproteinase-2 (MMP-2) activity in cultures of fibroblasts isolated from
      normal human skin. Fibroblasts exposure to varying doses of PTHrp for 48 h,
      significantly and dose-dependently inhibited proliferation evaluated by [(3)H]
      thymidine incorporation into DNA. A dose-dependent stimulation of cAMP released
      into the medium was concomitantly observed. In contrast, PTHrp had no effect on
      collagen synthesis evaluated either by [(3)H]-proline incorporation or by
      radioimmunoassay (RIA) of the carboxyterminal fragment of type I procollagen
      (PICP). MMP-2 activity, evaluated by quantitative zymographic analysis, was
      significantly increased by PTHrp treatment at doses of 160 and 320 nM. These
      findings indicate that PTHrp may play a role in normal dermal physiology by
      controlling both fibroblast proliferation and extracellular matrix degradation.

PMID- 12190939
TI  - Integrin expression in the dermis during scar formation in humans.
AB  - To evaluate changes leading to human wound reorganization we examined by
      immunohistochemistry the expression of several extracellular matrix (ECM)
      receptors (alpha2 chain of VLA-2, alpha3 chain of VLA-3, alpha6 chain of VLA-6,
      alphav, and beta1/beta3 chains of integrins) in a series of biopsies of human
      skin wounds healing by primary intention. The first time point investigated in
      this study was day 6 after injury, i.e. when a fibrin clot has been almost
      completely replaced by the granulation tissue. Gradual changes in integrin
      expression in granulation tissue and in the dermal scar were observed from the
      first time point investigated and were characterized by an up-regulation of
      alpha2beta1 complex, alphav integrin subunit, and beta1 integrin subunit. At day
      27, the expression of the alpha2 chain of VLA-2 in the scar decreased. The
      expression of alphav and beta1 integrin subunits decreased but was still
      detectable by day 35. Vitronectin expression from day 7 onwards was also
      increased and colocalized to the area of the wounded dermis, and decreased by day
      27. Our data suggests that, during the remodelling of the provisional matrix of
      the wound, dermal fibroblasts express transiently mainly alpha2 and alphav
      subunits of integrins associated with up-regulation of the beta1 subunit. It
      seems that up-regulation of some chains of integrins may be involved in the
      control of deposition of ECM components associated with wound healing.

PMID- 12190940
TI  - A large conductance [Ca(2+)](i)-independent K(+) channel expressed in HaCaT
      keratinocytes.
AB  - Patch-clamp recordings were carried out in the inside-out configuration in human
      keratinocytes of the cell line HaCaT. Patch pipettes were filled with 150 mM KCl,
      1 mM CaCl(2) and 10 mM HEPES. In symmetrical KCl solutions, single channel
      currents from a large conductance channel (about 170 pS) were measured.
      Replacement of 120 mM KCl by K-aspartate had only a minor influence on the single
      channel conductance and on the reversal potential. In intracellular solution in
      which K(+) has been replaced by Na(+) or NMDG(+), the reversal potential shifted
      to > + 40 mV indicating K(+) as the main charge carrier. The channels were
      neither dependent on intracellular Ca(2+) (between 0.8 nM and 10 micro M), ATP
      (at 0 and 1 mM) nor Mg(2+) (at 0 and 0.5 mM). The mean current showed an outward
      rectification that can be mainly attributed to the voltage dependence of the open
      probability. The channels displayed bursting kinetics with a mean open time of
      about 2 ms and closed times of about 0.2, 2 and 20 ms. The mean open probability
      was usually low (0.05) but increased occasionally (0.6) mainly due to a lower
      probability of long closings. We conclude that these K(+) channels contribute to
      the resting potential of human keratinocytes which may control the Ca(2+) influx
      and thereby their proliferation and differentiation.

PMID- 12190941
TI  - Absence of the granular layer and keratohyalin define a morphologically distinct
      subset of individuals with ichthyosis vulgaris.
AB  - The clinical diagnosis of ichthyosis vulgaris (IV) can be difficult.
      Abnormalities in the granular layer and the ultrastructure of keratohyalin
      granules (KHG) suggest that morphology may be helpful. To clarify morphologic
      findings in IV, 41 clinically affected individuals and 21 unaffected family
      members or age- and sex-matched controls were studied by light microscopy. In
      these, the granular layer was totally absent in approximately 50% of affected
      individuals, while present in all controls. Forty-seven individuals in the light
      microscopy group were also studied by electron microscopy. Keratohyalin granules
      were absent in all affected individuals lacking the granular layer by light
      microscopy. Clinical severity usually correlated with the lack of a granular
      layer and KHG. Absence of the granular layer was consistent in different anatomic
      sites and in serial biopsies taken over a 1-3-year period. In a subset of
      clinically affected, unrelated subjects with moderate to severe involvement, four
      out of 11 (36%) had similar findings. Keratinocytes cultured from affected
      individuals with no KHG expressed virtually no detectable profilaggrin protein in
      vitro. The data suggest that a subset of individuals with moderate to severe IV
      have a consistently absent granular layer and KHG. Absence of the granular layer
      and lack of KHG correlated almost perfectly; thus light microscopy offers a
      convenient means of identifying this subtype of IV. However, both morphologic
      types of IV were observed within single families. Therefore, the relationship
      between granular layer abnormalities and IV is complex and requires the study of
      more affected families. One interpretation of the data is that IV is a multigenic
      disorder in which one of the genes alters profilaggrin expression. We propose
      this clinical and histologic phenotype as useful for identifying the gene(s)
      involved and also for determining whether it represents a modifier or a major
      locus of the disorder.

PMID- 12190942
TI  - Decreased IL-10 production by psoriatic peripheral blood mononuclear cells
      stimulated with streptococcal superantigen.
AB  - The strong association of acute guttate psoriasis and streptococcal throat
      infection has suggested a role for streptococcal antigens in the pathogenesis of
      psoriasis. We have reported that psoriatic peripheral blood mononuclear cells
      (PBMCs) showed significantly lower responses to cytoplasmic membrane-associated
      protein (CAP) isolated from group A beta-hemolytic streptococci, a kind of
      streptococcal superantigen. The objectives were to evaluate the abnormal cytokine
      production by psoriatic PBMCs to streptococcal superantigen, CAP. We compared the
      production of four different cytokines, i.e. IL-4, IL-5, IL-10, and IFN-gamma, by
      PBMCs between psoriatic patients and healthy controls after stimulation with CAP
      or two different staphylococcal superantigens, staphylococcal enterotoxin A (SEA)
      or E (SEE). When PBMCs were stimulated with CAP, the production of IL-10 was
      significantly lower by psoriatic PBMCs than by those from healthy controls,
      whereas those of IL-4, IL-5, or IFN-gamma were not different between the two
      groups. Such a significant decrease in IL-10 production by psoriatic PBMCs was
      not observed when they were stimulated with staphylococcal superantigens. Flow
      cytometric analysis of intracytoplasmic IL-10 demonstrated defective IL-10
      production by psoriatic PBMCs in both CD3+ T cells and CD14+ monocytes. There was
      a significant positive correlation between IFN-gamma production by PBMCs and the
      proliferation of Vbeta8+ T cells preferentially stimulated by CAP. These data
      demonstrating the defective IL-10 production by psoriatic PBMCs stimulated with
      streptococcal superantigen seem to explain why only psoriatic patients evolve
      sustained and Th-1 deviated skin lesions after streptococcal upper respiratory
      infection.

PMID- 12190943
TI  - Dual role of protein kinase C on mitogen-activated protein kinase activation and
      human keratinocyte proliferation.
AB  - Subconfluent normal human keratinocytes exhibit autonomous (autocrine growth
      factor driven) proliferation and express the specific markers for keratinocyte
      proliferation K#5 and K#14. In keratinocyte autocrine culture, the exogenously
      added epidermal growth factor (EGF) has no effect on cell proliferation and
      mitogen-activated protein kinase (MAPK) activity. PD98059 inhibits MAPK pathway
      and autocrine keratinocyte proliferation. Staurosporine and Go6976 strongly
      inhibit autonomous keratinocyte proliferation. In contrast, Go6983 (which does
      not inhibit PKC micro ) inhibits only 20% of autocrine keratinocyte
      proliferation. Staurosporine inhibits MAPK activity, whereas Go6976 and Go6983
      strongly increase it. We have concluded that MAPK, PKC micro and probably
      PKCalpha take part in autocrine keratinocyte proliferation. The effect of Go6976
      and Go6983 on MAPK activity could be explained by the inhibition of PKC-dependent
      MAPK-phosphatase expression. The effect of staurosporine could be explained by
      its paradoxical action (activation) on protein kinase C (PKC) in keratinocytes.

PMID- 12190945
TI  - Epidermal CD8+ T cells reactive with group A streptococcal antigens in chronic
      plaque psoriasis.
AB  - Chronic plaque psoriasis is a T cell mediated disease associated with group A
      streptococci (GAS). We have previously shown the presence of a psoriasis-specific
      dermal Th1 subset that recognizes GAS antigens. To assess whether GAS-reactive T
      cells are also present in lesional epidermis, fresh cell suspensions or T cell
      lines isolated from lesional epidermis of 33 psoriasis patients were stained for
      intracellular interferon-gamma after stimulation with GAS antigens. The patients
      were typed by PCR for HLA-DR7 and HLA-Cw6 expression. A subset of GAS-reactive
      CD8+ T cells (2.4% +/- 2.4) was found in 14/21 (67%) fresh cell suspensions. A
      smaller subset of GAS-reactive CD4+ T cells (0.9% +/- 0.9) was found in 13/21
      (62%) fresh cell suspensions, which was expanded in the T cell lines. There was a
      significant inverse correlation between the proportions of GAS-reactive CD4+ and
      CD8+ T cells in the fresh suspensions (r = -0.48, P = 0.0277). The presence of
      GAS-reactive CD4+ or CD8+ T cells did not correlate with HLA-DR7 or HLA-Cw6
      expression, respectively. This study has demonstrated GAS-reactive CD8+, and to a
      lesser extent CD4+, T cell subsets in psoriatic epidermis and provides further
      evidence that GAS antigens may play a role in the pathogenesis of chronic plaque
      psoriasis.

PMID- 12190944
TI  - Similar UV responses are seen in a skin organ culture as in human skin in vivo.
AB  - Ultraviolet radiation (UVR) plays an important role in the development of non
      melanoma skin cancer. Most tumors develop in chronically sun-exposed skin, most
      often in cosmetically sensitive locations, where in vivo experiments may be
      difficult to perform. In this study, we describe a skin organ culture model with
      preserved normal morphology and intact response to UVR. Skin explants from
      chronically sun-exposed and non-sun-exposed skin were irradiated with artificial
      UVA+UVB with and without topical sunscreen. UV-induced DNA damage, epidermal p53
      response and repair kinetics were analyzed using immunohistochemistry. Four hours
      after UV-irradiation epidermal keratinocytes showed a strong immunoreactivity for
      thymine-dimers. Gradual repair during an incubation time resulted in few residual
      thymine-dimers after 48 h. Repair appeared to be more efficient in chronically
      sun-exposed skin compared with non-sun-exposed skin. There was also an
      accumulation of p53 protein in epidermal keratinocytes, peaking at 4-24 h after
      irradiation. Large interindividual differences with respect to formation and
      repair of thymine-dimers as well as induction and duration of the p53 response
      were observed. Skin explants treated with topical sunscreen prior to UV
      irradiation showed a clear reduction of thymine-dimers and p53 expression. The
      epidermal UV-responses and repair kinetics in organ-cultured skin were similar to
      what was found in vivo. Our data suggest that organ-cultured skin provides a
      valuable tool for studies of UV-induced epidermal responses in chronically sun
      exposed skin.

PMID- 12190946
TI  - Stimulation of Kaposi's sarcoma cell growth by urine from women in early
      pregnancy, the current source for clinical-grade human chorionic gonadotropin
      preparations.
AB  - Clinical-grade preparations of human chorionic gonadotropin (hCG) have been shown
      to be toxic to Kaposi's sarcoma (KS) cells. However, the results of clinical
      studies using commercial hCG preparations KS remain highly contradictory. More
      particularly, some hCG preparations could have a paradoxical growth effect on KS.
      Such discrepant results may be explained by the fact that the anti-KS activity is
      not associated with hCG itself but with one or more factors that are co-purified
      with the hormone. We found here that crude urine from first trimester pregnant
      women, the current source for commercial hCG, had a growth stimulatory effect on
      KS cells. By contrast, urine from last trimester pregnant women, from non
      pregnant young women, from menopausal women and from men exhibited neither a
      growth stimulatory nor a growth inhibitory effect on KS cells. The amplitude of
      this pregnancy urine-associated pro-KS activity/hCG unit was higher than that
      achieved with clinical-grade hCG preparations. Partial co-purification of
      pregnancy-associated factors during the extraction procedure of commercial hCG
      from urine may explain the pro-KS activity achieved with some hCG preparations.
      We, therefore, suggest a cautious use of hCG purified from pregnancy urine for
      the treatment of KS.

PMID- 12190947
TI  - The effect of topically applied salicylic compounds on serotonin-induced
      scratching behaviour in hairless rats.
AB  - There is a strong need for antipruritic substances for treating itch in clinical
      dermatology. In one recent human study, topically applied acetylsalicylic acid
      has been described to rapidly decrease histamine-induced itch. We have
      established a model for periferally elicited pruritus by injecting serotonin into
      the rostral back area (neck) in rats. Using this model, we aimed to investigate
      the antipruritic potential of four different salicylic compounds, which all
      possess different skin penetration characteristics. Eighteen rats were studied
      for 6 weeks. Prior to serotonin injections (2 mg/ml, 50 micro l), 10 micro l of
      test substances was applied to a circular area 18 mm in diameter. The four
      substances were salicylic acid, butyl salicylate, diethylamine salicylate and
      salicylamide, all solubilized in dimethyl isosorbide to a concentration of 5%
      w/w. Diethylamine salicylate and salicylamide were previously shown to be slowly
      absorbed through rat skin in contrast to salicylic acid and butyl salicylate.
      After serotonin injections, scratching was monitored by video recording for 1.5
      h. Compared with the vehicle, a lower number of scratch sequences were seen when
      diethylamine salicylate (P < 0.001) and salicylamide (P = 0.005) had been
      applied. The numbers of scratch sequences were lower with diethylamine salicylate
      and salicylamide than with the vehicle throughout the 1.5-h study period. We
      conclude that topical application of diethylamine salicylate and salicylamide
      could suppress serotonin-induced scratching in rats. The antipruritic effect
      seems to be related to the slow drug release of the two substances. The results
      may be clinically relevant as serotonin induces itch in humans.

PMID- 12190948
TI  - 17alpha-estradiol induces aromatase activity in intact human anagen hair
      follicles ex vivo.
AB  - For topical treatment of androgenetic alopecia (AGA) in women, solutions
      containing either estradiol benzoate, estradiol valerate, 17beta- or 17alpha
      estradiol are commercially available in Europe and some studies show an increased
      anagen and decreased telogen rate after treatment as compared with placebo. At
      present it is not precisely known how estrogens mediate their beneficial effect
      on AGA-affected hair follicles. We have shown recently that 17alpha-estradiol is
      able to diminish the amount of dihydrotestosterone (DHT) formed by human hair
      follicles after incubation with testosterone, while increasing the concentration
      of weaker steroids such as estrogens. Because aromatase is involved in the
      conversion of testosterone to estrogens and because there is some clinical
      evidence that aromatase activity may be involved in the pathogenesis of AGA, we
      addressed the question whether aromatase is expressed in human hair follicles and
      whether 17alpha-estradiol is able to modify the aromatase activity. Herewith we
      were able to demonstrate that intact, microdissected hair follicles from female
      donors express considerably more aromatase activity than hair follicles from male
      donors. Using immunohistochemistry, we detected the aromatase mainly in the
      epithelial parts of the hair follicle and not in the dermal papilla. Furthermore,
      we show that in comparison to the controls, we noticed in 17alpha-estradiol
      incubated (1 nM) female hair follicles a concentration- and time-dependent
      increase of aromatase activity (at 24 h: 1 nM = +18%, 100 nM = +25%, 1 micro M =
      +57%; 24 h: 1 nM = +18%, 48 h: 1 nM = +25%). In conclusion, our ex vivo
      experiments suggest that under the influence of 17alpha-estradiol an increased
      conversion of testosterone to 17beta-estradiol and androstendione to estrone
      takes place, which might explain the beneficial effects of estrogen treatment of
      AGA.

PMID- 12190949
TI  - Simple and rapid method to isolate and culture follicular papillae from human
      scalp hair follicles.
AB  - Study of the involvement of the hair follicle papilla in hair growth regulation
      was greatly facilitated by the isolation and cultivation of this tiny cluster of
      fibroblast-like cells in the rat vibrissae and in the human hair follicle. While
      isolation of the hair follicle papilla from the former is relatively
      straightforward, the current method to isolate the much smaller human hair
      follicle requires significant skill. Thus, the routine initiation of primary
      cultures of human scalp hair follicle papilla cells requires significant
      training, time, and commitment. In an attempt to simplify hair follicle papilla
      cell culture methodology for new laboratory personnel, we have made significant
      refinements to the current method. Our method requires only two simple
      manipulations to isolate hair follicle papilla from intact isolated hair
      follicles. This very rapid and easy method isolates clean and intact hair
      follicle papillae. Together with their attachment via scratching to the growth
      surface, the isolation and cultivation of this important hair follicle component
      can now be achieved easily by the laboratory newcomer. The method relies for its
      simplicity on the removal of the hair follicle papilla from the outside of the
      intact hair follicle rather than via internal manipulations from within the hair
      follicle.

PMID- 12190951
TI  - Statins and bone turnover.

PMID- 12190952
TI  - Variability of Nt-proANP and C-ANP.
AB  - BACKGROUND: Natriuretic peptides are frequently measured in patients with chronic
      cardiac failure (CCF). We set out to compare the variability of atrial
      natriuretic peptide (C-ANP) and its precursor N-terminal pro-ANP (Nt-proANP) to
      decide which would be more suitable for routine use. METHODS: Ten males with
      compensated CCF (age range 62-76 years) were studied, with matched controls.
      Blood was withdrawn every 2 min for 90 min from a forearm vein, and plasma C-ANP
      and Nt-proANP were measured by radioimmunoassay. RESULTS: Levels were elevated in
      the patient group [C-ANP: median 268 (range 171-423) vs. 40 (28-56) ng L-1, P <
      0.0002 Mann-Whitney U-test; Nt-proANP: 1955 (562-4451) vs. 621 (409-961) pmol L
      1, P < 0.003]. A similar number of 'peaks' was observed in both groups with both
      peptides, about one every 10 min, and their relative height was similar in both
      groups. Variability was greater for C-ANP than for Nt-proANP in both patients
      [coefficient of variation of means 51 (range 36-70) vs. 3.6 (2.1-6.2)%, P < 0.01;
      sign test] and controls [65 (49-83) vs. 8.9 (4.7-13.5)%, P < 0.01]. CONCLUSION:
      Nt-proANP is less variable than C-ANP and hence more suited for diagnostic or
      prognostic use.

PMID- 12190953
TI  - The relation between Helicobacter pylori and atherosclerosis cannot be explained
      by a high homocysteine concentration.
AB  - BACKGROUND: Recent studies have suggested that a chronic infection with
      Helicobacter pylori might be an independent risk factor for atherosclerosis.
      However, a direct role in atherogenesis is not plausible, since the bacterium has
      not been isolated from atherosclerotic lesions. An indirect mechanism that could
      link H. pylori with atherosclerosis might be through an increase in plasma
      homocysteine concentration caused by deficiencies of vitamin B12 and folate in
      plasma. MATERIALS AND METHODS: In 150 female patients with peripheral arterial
      disease (PAD) and in 412 healthy control women from a nation-wide population
      based case-control study, blood samples were collected to determine the antibody
      titre against H. pylori and to measure plasma homocysteine, folate and vitamin
      B12 levels. First, the odds ratio for PAD in women with a positive antibody titre
      against H. pylori was calculated and adjusted for homocysteine level. Secondly,
      mean concentrations of vitamin B12, folate and homocysteine were compared in
      healthy controls with a positive or negative antibody titre against H. pylori.
      Thirdly, the relation between H. pylori and PAD in individuals with a normal or
      high homocysteine level was investigated. RESULTS: A positive immunoglobulin G
      antibody titre against H. pylori was found in 42% of the PAD patients and in 27%
      of the controls. The age- and socio-economic-status (SES) adjusted odds ratio for
      PAD was 1.5 (95%CI; 1.0-2.2). Additional adjustment for homocysteine plasma
      concentration did not essentially change the odds ratio. Secondly, among the
      healthy controls, the homocysteine plasma concentration did not depend on the
      immunoglobulin G titre, neither did the folate plasma concentration. The
      concentration of vitamin B12 was slightly higher in women with a positive titre.
      Thirdly, H. pylori infection was a risk factor for PAD in subjects with a normal
      homocysteine concentration [OR 2.0 (95%CI 1.3-3.1)]. CONCLUSIONS: This study
      shows a relationship between a positive immunoglobulin G antibody titre against
      H. pylori and PAD in young women. Moreover, this study does not support the
      hypothesis that H. pylori infection is related to atherosclerosis via an increase
      in plasma homocysteine concentration.

PMID- 12190954
TI  - Effect of endothelin-1 on intracellular glutathione and lipid peroxide
      availability and on the secretion of vasoactive substances by human umbilical
      vein endothelial cells.
AB  - BACKGROUND: The major pathophysiologic changes observed in preeclampsia suggest
      that endothelial cell dysfunction plays an important role in this disorder. The
      pathway mediating endothelial cell layer dysfunction is unknown. The
      concentration of endothelin-1 (ET-1), a potent mammalian vasoconstrictor peptide
      produced by the vascular endothelium, has been observed to be significantly
      increased in preeclampsia. In this study, we determined the in vitro effect of
      endothelin-1 on glutathione and lipid peroxide levels and on the secretion of
      vasoactive substances by human umbilical vein endothelial cells (HUVECs).
      METHODS: Human umbilical vein endothelial cells were incubated for 24 h in the
      presence of different concentrations of ET-1 (0-1000 pmol L(-1)), which were
      shown in an earlier experiment to have no effects on vitality and proliferation
      rate of HUVECs. The levels of glutathione (GSH) and lipid peroxides (LPO) were
      measured in endothelial cell lysates. For the measurement of vasoactive
      substances, levels of nitric oxide (NO), prostacyclin (PGI2) and thromboxane A2
      (TXA2) were measured in endothelial cell supernatants. RESULTS: At lower
      concentrations (5-50 pmol L(-1)), ET-1 increases the intracellular content of
      LPO, stimulates the secretion of TXA2, but inhibits the secretion of PGI2 in
      endothelial cells compared with control cells. At higher concentrations (100-1000
      pmol L(-1)), ET-1 increases the intracellular content of GSH, but results in a
      decrease of LPO, and increase of PGI2, back to control levels. ET-1 has no effect
      on NO secretion. CONCLUSION: These findings demonstrate that at concentrations
      corresponding to values in plasma from preeclamptic women, ET-1 induces oxidative
      stress and results in altered secretion of vasoactive substances in human
      endothelial cells. We conclude that ET-1 may participate in the pathway leading
      to endothelial cell dysfunction seen in preeclampsia.

PMID- 12190956
TI  - Gastric emptying in myotonic dystrophy.
AB  - BACKGROUND: Gastrointestinal symptoms are common and important for the quality of
      life in patients with myotonic dystrophy (MD). Gastric emptying was studied in
      patients with MD who suffered from symptoms suggesting slow gastric emptying and
      the effect of prokinetic treatment was evaluated. METHODS: Gastric emptying was
      studied in 10 patients with MD who were suffering from nausea, early satiety,
      bloating, regurgitation, vomiting, or abdominal pain using a (99)Tc-labelled test
      meal, and was compared with gastric emptying in a group of healthy controls. The
      patients were subsequently treated with erythromycin and their gastrointestinal
      symptoms were recorded and the gastric emptying test was repeated. RESULTS:
      Patients with MD had a significantly longer gastric lag phase (46.1 +/- 4.3 vs.
      31.9 +/- 4.0 min, P = 0.03), a slower emptying phase (7.1 +/- 0.9 vs. 10.2 +/-
      0.9 kJ min(-1), P = 0.02) and a longer half-emptying time, T50 (141.7 +/- 10.5
      vs. 98.6 +/- 8.7 min, P = 0.01) than a matched control group. Erythromycin did
      not stimulate the gastric emptying rate. The effect on gastrointestinal symptoms
      was modest, except for a reduction of diarrhoea. CONCLUSIONS: Patients with MD
      suffering from nausea, vomiting and early satiety, displayed a slow gastric
      emptying. Treatment with erythromycin had only moderate effect on gastric
      emptying or gastric symptoms, but reduced diarrhoea in a majority of the
      patients.

PMID- 12190955
TI  - Differential regulation of atrial and brain natriuretic peptides and its
      implications for the management of left ventricular volume overload.
AB  - BACKGROUND: In this study, we investigated the possibility that the atrial and
      brain natriuretic peptide expression in left ventricular volume overload (VOL) is
      transcriptionally regulated. We further evaluated the diagnostic and/or
      prognostic potential of this expression for the management of patients with this
      disorder. DESIGN: We compared the myocardial mRNA expression and plasma levels of
      the two peptides in VOL patients using donor hearts and in healthy blood donors
      as controls. RESULTS: The atrial natriuretic peptide (ANP) mRNA was elevated by
      38% (P < 0.03) in the right atrium and by 53% (P < 0.003) in the left atrium, but
      was unchanged in the ventricular chambers of the patient group (n = 19) compared
      with controls (n = 8). Plasma ANP concentration was elevated by 62% (P < 0.001)
      compared with blood donor controls (n = 79). It increased slightly (by 36%) 2 h
      following surgery, and remained at 64% higher (P < 0.03 vs. presurgery) for the 5
      days following surgery. The brain natriuretic peptide (BNP) mRNA was elevated by
      approximately one-fold in both the left ventricle (P < 0.02) and right atrium (P
      < 0.05), by 94% (P < 0.02) in the right ventricle and by 89% (P < 0.05) in the
      left atrium. Its plasma level in the patients was 3.4-fold (P < 0.00003) higher
      than in control subjects. It increased significantly by 1.2-fold (P < 0.01) 2 h
      following surgery, but dropped significantly (P < 0.05 vs. 2 h post surgery) to
      presurgical levels 5 days following surgery. CONCLUSION: The results show chamber
      specific elevation in both atrial and brain natriuretic peptide expression and
      differences in their circulating levels in VOL, suggesting that BNP is a
      potential prognostic indicator in the postsurgical management of these patients.

PMID- 12190957
TI  - Intestinal absorption and biliary secretion of ursodeoxycholic acid and its
      taurine conjugate.
AB  - BACKGROUND: Ursodeoxycholic acid (UDCA) and its taurine conjugate (TUDCA) exert a
      protective effect in cholestatic liver diseases. A greater hepatoprotective
      effect of TUDCA has been suggested. Absorption appears to be a limiting factor
      and up to now has not been studied in man. METHODS: We studied absorption and
      biliary bile acid secretion and composition after administration of UDCA and
      TUDCA in patients who had complete extrahepatic biliary obstruction caused by
      pancreatic carcinoma but had no intestinal or liver disease. After 5 days of
      intact enterohepatic circulation eight patients with a percutaneous biliary
      duodenal drainage received, during two study periods, 1000 mg (1916.9 micromol;
      mean 29.6 micromol kg(-1)) TUDCA and 750 mg (1910.4 micromol; mean 29.5 micromol
      kg(-1)) UDCA in random order. Each patient served as his own control. RESULTS:
      After UDCA and TUDCA administration the biliary UDCA content increased to 55.2%
      and 54.6% of total bile acids, respectively (not significant). Biliary secretion
      of cholic and chenodeoxycholic acids remained unchanged whereas that of
      lithocholic acid increased slightly. A total of 64.6% of the orally administered
      TUDCA and 55.1% of the UDCA was absorbed (not significant). After TUDCA
      administration, biliary UDCA was preferentially (95.4%) taurine-conjugated
      whereas after UDCA administration biliary UDCA was mainly (79.8%) glycine
      conjugated. CONCLUSIONS: After oral administration of TUDCA and UDCA, no
      significant differences in their absorption and in biliary bile acid secretion
      exist. Whether biliary enrichment with taurine conjugates of UDCA instead of
      glycine conjugates offers advantages in the treatment of cholestatic liver
      disease is unclear at present.

PMID- 12190959
TI  - Impaired system A amino acid transport mimics the catabolic effects of acid in L6
      cells.
AB  - BACKGROUND: Metabolic acidaemia stimulates protein catabolism in skeletal muscle
      cells, leading to muscle wasting. As this occurs without decreasing cytosolic pH,
      the initial signal is unclear. A possible explanation is that extracellular pH
      acts on solute transporters at the cell surface, inhibiting nutrient influx.
      DESIGN: Influx through glucose and Pi transporters and System A amino acid
      transporters into L6 skeletal muscle cells was assessed using 3H-2-deoxyglucose
      (2-DG), 33Pi and 14C-methylaminoisobutyrate (MeAIB), respectively. Protein
      degradation (PD) was assessed from 14C efflux from cells prelabelled with 14C
      Phe. Branched-chain amino acids and Phe were assayed by selective fluorimetric
      assays. RESULTS: While acid (pH 7.1) had little immediate effect on 2-DG or 33Pi
      influx, exposure to pH 7.1 rapidly inhibited MeAIB influx. To determine whether
      System A inhibition was sufficient to trigger PD, it was blocked at pH 7.5 by a
      saturating dose (10 mmol L(-1)) of nonmetabolisable substrate (MeAIB). Like acid,
      this increased PD and decreased total protein. It also mimicked the decreases in
      protein synthesis, DNA synthesis, glucose transport and glycolysis, and depletion
      of branched-chain amino acids and Phe, which are induced in L6 by acid. The onset
      of inhibition of PD by an extracellular Gln load was retarded at pH 7.1, and
      stimulation of PD by acid was negligible if PD had already been stimulated by Gln
      depletion. The stimulatory effect of MeAIB on PD was selectively blunted by an
      excess of Gln, whereas the inhibitory effect of Gln on PD was blocked by excess
      MeAIB. CONCLUSIONS: The similarity of changes in response to MeAIB and acid
      implies that these share a common intracellular signalling pathway triggered by
      inhibition of System A. Even though System A is only a minor contributor to total
      Gln influx in L6 cells, it is suggested that blockade of System A with acid or
      MeAIB induces a catabolic state by denying Gln access to a key intracellular
      regulatory site.

PMID- 12190958
TI  - Statins decrease bone turnover in postmenopausal women: a cross-sectional study.
AB  - BACKGROUND: Statins have been suggested as potential agents in the management of
      osteoporosis. Reviews of medical records have shown an increased bone mass and
      some studies have shown a reduced occurrence of fractures in subjects on long
      term treatment with statins. We studied the effects of treatment with statins on
      calcium homeostasis, bone turnover and bone mineral density. DESIGN: In a cross
      sectional design, plasma levels of parathyroid hormone (PTH) and biochemical
      markers of bone turnover, bone mineral density (BMD) and body composition (fat-
      and lean tissue-mass) were measured in 140 postmenopausal women who had been
      treated with a statin for more than 2 years (median 4 years) and compared to 140
      age- and gender-matched, population-based controls. RESULTS: Plasma levels of
      bone turnover markers were lower in the statin-treated subjects than in the
      controls: osteocalcin (-9%, P = 0.03), bone-specific alkaline phosphatase (-14%,
      P < 0.01), and C-terminal telopeptide of type I collagen (-11%, P < 0.01). On the
      other hand, plasma PTH levels were 16% higher in the statin-treated subjects than
      in the controls (P < 0.01). However, body composition and BMD at the lumbar
      spine, hip, forearm and whole body did not differ between the two groups. No
      correlation could be demonstrated between changes in biochemical quantities and
      dose or duration of statin use. CONCLUSION: Our data show that statins affect the
      function of bone cells. Most likely, the effect is antiresorptive.

PMID- 12190960
TI  - Long-term sequelae of HFE deletion in C57BL/6 x 129/O1a mice, an animal model for
      hereditary haemochromatosis.
AB  - BACKGROUND: HFE knockout mice (C57BL/6 x 129/Ola strain) mimic the functional
      aberrations of human hereditary haemochromatosis (HH) in short-term experiments.
      The present study investigates functional and morphological long-term changes.
      METHODS: HFE(o/o), HFE(+/o) and HFE(+/+) mice were maintained on iron-rich and
      control diets for 2 weeks, 3, 12 and 18 months. Light microscopic tissue iron
      distribution, pathomorphological alterations, tissue iron content and oxidative
      stress were analysed in liver, pancreas, spleen, gastrointestinal tract, kidneys
      and myocardium. Additionally, duodenal 59Fe absorption and 59Fe whole body loss
      were measured. RESULTS: Iron distribution between organs and microscopic iron
      deposition in the tissues resembled the patterns described in HH. After 3 months
      of iron-rich feeding duodenal 59Fe absorption decreased to approximately 15% of
      iron-adequate controls but remained about twice as high in HFE(o/o) as in
      HFE(+/+) mice. Hepatic iron concentrations reached only half the values known to
      induce hepatic fibrosis in rats and humans, while whole body 59Fe loss was about
      twice as high. Consequently no hepatic fibrosis developed, although massive
      hepatocellular iron deposition and indication for oxidative stress were observed.
      CONCLUSION: C57BL/6 x 129/O1a HFE(o/o) mice mimic HH iron distribution and the
      regulation of intestinal iron absorption after long-term feeding. However,
      characteristic morphological late changes in untreated HH are not modelled.

PMID- 12190961
TI  - Effects of hormone replacement therapy on blood platelets.
AB  - BACKGROUND: Hormone replacement therapy (HRT) increases the risk of
      cardiovascular morbidity in postmenopausal women under certain circumstances.
      Part of this effect may be the result of the influence of HRT on blood platelets.
      We studied the effect of short-term oral hormone replacement therapy (unopposed
      oestradiol or sequentially combined oestradiol and trimegestone or
      dydrogesterone) on platelet activation parameters in healthy postmenopausal
      women. DESIGN: We designed a prospective, randomised, placebo-controlled 12-week
      study. Sixty healthy, normotensive, nonhysterectomised, postmenopausal women
      received daily micronised oestradiol (E2) 2 mg (n = 16), or 2 mg E2 daily
      sequentially combined with either trimegestone 0.5 mg daily (n = 14) or
      dydrogesterone 10 mg daily (n = 14), or placebo (n = 16). Data on platelet
      activation were collected at baseline and after 12 weeks of treatment using flow
      cytometry. RESULTS: Twelve weeks of treatment with combined HRT was associated
      with an increase in platelet activation parameters P-selectin and glycoprotein 53
      (by 17% and 14%, respectively, P = 0.04 vs. the placebo group for both
      comparisons), suggesting alpha granule and lysosome degranulation. E2 replacement
      therapy was associated with an increase in P-selectin labelling by 22% (P = 0.04
      vs. the placebo group). CONCLUSION: Short-term treatment with oestradiol or
      combined HRT increases the amount of circulating activated platelets as measured
      by flow cytometry. This could be a mechanism by which short-term HRT might
      increase the risk of thrombosis.

PMID- 12190962
TI  - Interactions of human immunodeficiency virus-1 proteins with neurons: possible
      role in the development of human immunodeficiency virus-1-associated dementia.
AB  - Human immunodeficiency virus-1 (HIV-1)-associated dementia is a severe
      neurological complication of HIV-1 infection that affects 15-20% of the patients
      in the late stages of acquired immunodeficiency syndrome. HIV-1-associated
      dementia is most probably a consequence of HIV-1 infection of the brain rather
      than of an opportunistic pathogen. The exact mechanism by which the virus causes
      this disorder, however, is not completely understood. A number of HIV-1 proteins
      have been shown to be released from HIV-1-infected cells and/or to be present in
      the extracellular milieu in the HIV-1-infected brain. Moreover, these proteins
      have been shown to possess neurotoxic and/or neuromodulatory features in vitro.
      This review describes the possible direct interactions of the HIV-1 proteins
      gp120, gp41, vpr, tat, rev, vpu and nef with neurons, which might play a role in
      the development of HIV-1-associated dementia in vivo.

PMID- 12190963
TI  - Inhaled nitric oxide: more than a selective pulmonary vasodilator.
AB  - Because of its high diffusing capacity through the alveolar-blood barrier and its
      high selectivity for the pulmonary vasculature, inhaled nitric oxide (NO) has
      been recently shown to be a viable and efficient approach to restore pulmonary NO
      deficiency. The most relevant applications of inhaled NO are in infants with
      primary pulmonary hypertension or hypoxia. In these patients, inhaled NO improves
      gas exchange and ventilation-perfusion matching, reduces the length of
      hospitalization and is without severe detrimental effects. The use of inhaled NO
      has also been extended to adults with pulmonary hypertension and the acute
      respiratory distress syndrome. In addition, recent clinical evidence supported by
      data from animal models, shows beneficial extra-pulmonary effects of inhaled NO,
      including protection against myocardial ischaemia-reperfusion injury.

PMID- 12190964
TI  - Introduction: epilepsy in the world.

PMID- 12190966
TI  - Welcome: The WHO view and launch of the second phase of the Global Campaign
      Against Epilepsy.

PMID- 12190967
TI  - "Out of the shadows": a global campaign against epilepsy.

PMID- 12190968
TI  - The ILAE/IBE/WHO epilepsy global campaign history. International League Against
      Epilepsy. International Bureau for Epilepsy.

PMID- 12190969
TI  - Epilepsy in the world today: medical point of view.

PMID- 12190970
TI  - Epilepsy in the world today: the social point of view.

PMID- 12190971
TI  - "Out of the shadows": the political view.

PMID- 12190972
TI  - "Out of the shadows": the patient's view.

PMID- 12190973
TI  - Global Campaign Against Epilepsy:closing remarks.

PMID- 12190974
TI  - The global burden of epilepsy.
AB  - We briefly describe the Global Burden of Diseases (GBD) study, its goals, and
      some of its outcomes as related to neurologic and psychiatric disorders. The
      summary measure of population health DALYs (Disability Adjusted Life Years) are
      described, as well as the implications for neuropsychiatric disorders of changing
      health indicators and the move from mortality toward disability indicators. The
      pressing need for new measures for health is answered by the new WHO
      Classification of Functioning Disability and Health, ICF, and a brief summary of
      its basic principles is provided. Although a better understanding of the
      physical, social, and economic burden of epilepsy has moved this disorder higher
      on the world's agenda, epilepsy still has problems to be recognized as a public
      health priority. The implications of a shift toward considering the disability of
      epilepsy, as outlined in the the WHO World Health Report 2001, are important. The
      burden of epilepsy is high and, for the year 2000, accounts for approximately
      0.5% of the whole burden of diseases in the world.

PMID- 12190975
TI  - The psychosocial burden of epilepsy.

PMID- 12190976
TI  - Global Campaign Against Epilepsy:the treatment gap.
AB  - A simple definition of the treatment gap is the number of people with a condition
      or disease who need treatment for it but who do not get it. It is an
      underutilised measure of health care. In epilepsy, it has been estimated by the
      direct method, during prevalence studies, and indirectly from the amount of
      antiepileptic drugs consumed in the country and the number of people with active
      epilepsy. The treatment gap in epilepsy is very high in the developing world.
      Possible causes of the treatment gap have been listed, but these have not been
      investigated.

PMID- 12190977
TI  - Global Campaign Against Epilepsy. Overview of the demonstration projects.

PMID- 12190978
TI  - Global Campaign Against Epilepsy. Regional declarations and white papers.

PMID- 12190979
TI  - European declaration on epilepsy October 25, 1998.

PMID- 12190980
TI  - Declaration of Santiago on epilepsy in Latin America.

PMID- 12190981
TI  - Asian-Oceanian declaration on epilepsy New Delhi, November 13, 2000.

PMID- 12190982
TI  - African declaration on epilepsy.

PMID- 12190983
TI  - Epilepsy in children and adolescents.

PMID- 12190984
TI  - Marshall Barber and the century of microinjection: from cloning of bacteria to
      cloning of everything.
AB  - A hundred years ago, Dr. Marshall A. Barber proposed a new technique - the
      microinjection technique. He developed this method initially to clone bacteria
      and to confirm the germ theory of Koch and Pasteur. Later on, he refined his
      approach and was able to manipulate nuclei in protozoa and to implant bacteria
      into plant cells. Continuous improvement and adaptation of this method to new
      applications dramatically changed experimental embryology and cytology and led to
      the formation of several new scientific disciplines including animal cloning as
      one of its latest applications. Interestingly, microinjection originated as a
      method at the crossroad of bacteriology and plant biology, demonstrating once
      again the unforeseen impact that basic research in an unrelated field can have on
      the development of entirely different disciplines.

PMID- 12190985
TI  - The molecular control of renal branching morphogenesis: current knowledge and
      emerging insights.
AB  - Mammalian kidney development requires the formation of a patterned, branched
      network of collecting ducts, a process termed renal branching morphogenesis.
      Disruption of renal branching morphogenesis during human kidney development
      results in renal dysplasia, the major cause of renal failure in young children.
      Genetic evidence, combined with in vitro data, have implicated transcription
      factors, secreted growth factors, and cell surface signaling peptides as critical
      regulators of renal branching morphogenesis. This review discusses the current
      knowledge regarding the regulation of renal branching morphogenesis in vivo
      provided by the analysis of genetic mutations in mice and humans which disrupt
      collecting duct system development. In addition, in vivo and in vitro evidence
      regarding the functions of several other gene families are considered, rendering
      new insight into emerging regulatory roles for these molecules in renal branching
      morphogenesis.

PMID- 12190986
TI  - Differentiation potential of primary myogenic cells derived from skeletal muscle
      of dystonia musculorum mice.
AB  - The dystonia musculorum (dt) mouse has a mutation in the gene encoding the
      cytoskeletal crosslinker protein bullous pemphigoid antigen 1 (Bpag1). These mice
      have perturbations in the cytoarchitecture of skeletal muscle. Bpag1 has been
      hypothesized to be involved in the maintenance rather than the establishment of
      the muscle cell architecture given that cytoskeletal disruptions are observed in
      the muscle tissue of post-natal dt mice. Not known is whether Bpag1-deficiency
      affects the proliferative and differentiation potential of myogenic cells. In the
      present investigation, we show that the growth rate of cultured primary myogenic
      cells derived from dt mice, as assessed by BrdU incorporation, is similar to that
      of myogenic cells derived from wild-type littermates. The myogenic
      differentiation potential of dt versus wild-type cells was monitored by examining
      the expression of myosin heavy chain by immunofluorescence, and by analyzing the
      expression profiles of myogenic regulatory factors and myogenic differentiation
      markers by RT-PCR. In all instances, both dt and wild-type myogenic cells
      displayed a similar differentiation profile. Furthermore, the absence of any
      observable differences in the proliferation and differentiation rates of dt and
      wild-type cells was not due to an overexpression of plectin, another crosslinker
      protein, in dt cells. Together, these findings demonstrate that the early phases
      of myogenic differentiation occur independently of Bpag1.

PMID- 12190987
TI  - PKC-regulated myogenesis is associated with increased tyrosine phosphorylation of
      FAK, Cas, and paxillin, formation of Cas-CRK complex, and JNK activation.
AB  - Previous reports suggest that PKC plays an important role in regulating
      myogenesis. However, the regulatory signaling pathways are not fully understood.
      We examined the effects of PKC downregulation on signaling events during skeletal
      muscle differentiation. We found that downregulation of PKC results in increased
      myogenesis in C2C12 cells as measured by creatine kinase activity and myogenin
      expression. We showed that, during differentiation, downregulation of PKC
      expression results in increased tyrosine phosphorylation of FAK, Cas, and
      paxillin, concomitant with enhanced Cas-CrkII complex formation, which leads to
      activation of JNK2. But in proliferated muscle cells, PKC inhibition results in
      FAK and Cas tyrosine dephosphorylation. Further, disruption of actin cytoskeleton
      by cytochalasin D prevents the activation of FAK and Cas as well as the formation
      of Cas-CrkII complex stimulated by PKC downregulation during muscle cell
      differentiation. Finally, we observed that PKC downregulation increases the
      tyrosine phosphorylation of focal adhesion associated proteins. Based on the
      above data, we propose that PKC downregulation results in enhanced tyrosine
      phosphorylation of FAK, Cas, and paxillin, thus promoting the establishment of
      Cas-CrkII complex, leading to activation of JNK and that these interactions are
      dependent upon the integrity of actin cytoskeleton during muscle cell
      differentiation. Data presented here significantly contribute to elucidating the
      regulatory role of PKC in myogenesis possibly through integrin signaling pathway.

PMID- 12190988
TI  - Correlates of developmental cell death in Dictyostelium discoideum.
AB  - We have studied the correlates of cell death during stalk cell differentiation in
      Dictyostelium discoideum. Our main findings are four. (i) There is a gradual
      increase in the number of cells with exposed phosphatidyl serine residues, an
      indicator of membrane asymmetry loss and increased permeability. Only presumptive
      stalk cells show this change in membrane asymmetry. Cells also show an increase
      in cell membrane permeability under conditions of calcium-induced stalk cell
      differentiation in cell monolayers. (ii) There is a gradual fall in mitochondrial
      membrane potential during development, again restricted to the presumptive stalk
      cells. (iii) The fraction of cells showing caspase-3 activity increases as
      development proceeds and then declines in the terminally differentiated fruiting
      body. (iv) There is no internucleosomal cleavage of DNA, or DNA fragmentation, in
      D. discoideum nor is there any calcium- and magnesium-dependent endonucleolytic
      activity in nuclear extracts from various developmental stages. However, nuclear
      condensation and peripheralization does occur in stalk cells. Thus, cell death in
      D. discoideum shows some, but not all, features of apoptotic cell death as
      recognized in other multicellular systems. These findings argue against the
      emergence of a single mechanism of 'programmed cell death (PCD)' before
      multicellularity arose during evolution.

PMID- 12190989
TI  - Type I keratin cDNAs from the rainbow trout: independent radiation of keratins in
      fish.
AB  - Five different type I keratins from a teleost fish, the rainbow trout
      Oncorhynchus mykiss, have been sequenced by cDNA cloning and identified at the
      protein level by peptide mass mapping using MALDI-MS. This showed that the entire
      range of type I keratins detected biochemically in this fish has now been
      sequenced. Three of the keratins are expressed in the epidermis (subtype Ie),
      whereas the other two occur in simple epithelia and mesenchymal cells (subtype
      Is). Among the Is keratins is an ortholog of human K18; the second Is polypeptide
      is clearly distinct from K18. We raised a new monoclonal antibody (F1F2, subclass
      IgG1) that specifically recognizes trout Is keratins, with negative reactions on
      zebrafish. A phylogenetic tree has been constructed from a multiple alignment of
      the rod domains of the new sequences together with type I sequences from other
      vertebrates such as shark, zebrafish, and human; a recently sequenced lamprey Is
      keratin was applied as outgroup. This tree shows one branch defining the K18
      orthologs and a second branch containing all other type I keratins (mostly
      subtype Ie). Within this second branch, the teleost keratins form a separate,
      highly bootstrap-supported twig. This tree leaves little doubt that the teleost
      Ie keratins diversified independently from the mammalian Ie keratins.

PMID- 12190990
TI  - Type II keratin cDNAs from the rainbow trout: implications for keratin evolution.
AB  - From a teleost fish, the rainbow trout Oncorhynchus mykiss, we have cloned and
      sequenced cDNAs encoding five different type II keratins. The corresponding
      protein spots, as separated by 2D-PAGE of trout cytoskeletal preparations, have
      been identified by peptide mass mapping using MALDI mass spectrometry. Three of
      the sequenced keratins are expressed in the epidermis (subtype IIe), and two in
      simple epithelia and mesenchymal cells (subtype IIs). The IIs keratins are both
      orthologs of human K8. This leaves unsequenced only the trace component S3 of the
      biochemically established trout keratin catalog. A phylogenetic tree has been
      constructed from a multiple alignment of the rod domains of the new keratin
      sequences together with type II sequences from other vertebrates such as shark,
      zebrafish, and human; lamprey K8 (recently sequenced in our laboratory) has been
      used as outgroup. This tree suggests, in a highly bootstrap-supported manner,
      that the teleost IIe keratins diversified independently from the mammalian IIe
      keratins. In contrast, all the species investigated express K8-like keratins,
      suggesting that the different IIe branches evolved from K8-like progenitors. The
      tree also indicates that the published zebrafish sequences represent IIe keratins
      and that the biochemically identified K8 ortholog in zebrafish has not yet been
      sequenced.

PMID- 12190991
TI  - DIGAMI (Diabetes Mellitus, Insulin Glucose Infusion in Acute Myocardial
      Infarction): theory and practice.

PMID- 12190992
TI  - Efficacy, effectiveness and safety of sulphonylurea-metformin combination therapy
      in patients with type 2 diabetes.

PMID- 12190993
TI  - Relationship of glycation, antioxidant status and oxidative stress to vascular
      endothelial damage in diabetes.
AB  - AIMS: To examine the inter-relationships of various microvascular pathogenic
      mechanisms in diabetic patients. METHODS: Patients with diabetes (n = 18) and non
      diabetic subjects (n = 18) were studied. RESULTS: Blood markers of glycaemic
      control and glycation differed between the two groups (glucose 10.9 +/- 7.6 vs.
      4.7 +/- 0.63 mmol/l, p < 0.01; HbA1c 7.0 +/- 1.3 vs. 4.5 +/- 0.3%, p < 0.001;
      glycated LDL 8.8 +/- 2.5 vs. 6.1 +/- 1.2%, p < 0.001) but plasma antioxidant
      status did not. LDL oxidation resistance, measured as lag time to maximum
      oxidation initiated by copper ions, was decreased in diabetes (58. +/- 14.3 vs.
      76.3 +/- 21.5 min, p < 0.01). Both soluble intercellular adhesion molecule-1
      (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1), markers of endothelial
      dysfunction, were significantly higher in diabetes (ICAM 491 +/- 128 vs. 403 +/-
      131 micro g/l, p < 0.05; VCAM 546 +/- 157 vs. 393 +/- 106 micro g/l, p < 0.01).
      Linear correlations were significant between HbA1c and lag time of LDL oxidation
      (r = -0.39, p < 0.05), ICAM (r = 0.40, p < 0.05) and VCAM (r = 0.38, p < 0.05).
      LDL oxidizability correlated with vitamin C (r = 0.51, p < 0.01) but not any
      adhesion molecule. In multivariate analysis, both ICAM and VCAM correlated with
      HbA1c only (r(2) = 0.16, F = 6.3, p < 0.01; r(2) = 0.14, F = 5.4, p < 0.01
      respectively). CONCLUSION: In diabetes, glycation, tissue oxidation and
      endothelial function are all abnormal and predisposing to microvascular
      complications but interrelationships are complex with glycation appearing most
      direct.

PMID- 12190994
TI  - Substitution of Dmo1 with normal alleles results in decreased manifestation of
      diabetes in OLETF rats.
AB  - AIM: Dmo1 (Diabetes Mellitus OLETF type I) is a major quantitative trait locus
      for dyslipidaemia, obesity and diabetes phenotypes in the Otsuka Long Evans
      Tokushima Fatty (OLETF) rat strain. To evaluate possible metabolic and
      pathological improvements generated by correction of the Dmo1 genetic pathway, we
      produced congenic lines, in which both OLETF Dmo1 alleles are replaced by the
      F344-derived genome. METHODS: Congenic animals were produced by introgressing
      F344-derived Dmo1 alleles into the OLETF rat. Congenic animals of the fourth
      generation (BC4) were intercrossed to obtain F1 animals (BC4:F1). Animals of the
      next generation, BC4:F2, were used for this study. We used 23 BC4:F2 males
      harbouring homozygous replacement of the OLETF Dmo1 region with the F344-derived
      genome. Seven animals with OLETF-derived Dmo1 alleles were used as controls.
      RESULTS: Dmo1-F344/F344 congenic rats showed significant decreases in body
      weight, abdominal fat weight, serum triacylglycerols, total cholesterol, food
      consumption and blood glucose after glucose loading (13%, 39%, 45%, 27%, 18% and
      27% respectively; p < 0.05) compared with Dmo1-OLETF/OLETF animals. Furthermore,
      histopathological analysis of the kidney showed that mesangial sclerosis, hyalin
      deposits and deposition of PAS-positive substance were significantly lower in
      Dmo1-F344/F344 animals (p < 0.05). CONCLUSION: Improvements in metabolic
      parameters and histopathological scores show that correction of the Dmo1 genetic
      pathway in the diabetic and mildly obese OLETF rat strain produces wide-ranging
      therapeutic effects. Thus, this pathway might represent a new drug target also
      applicable to humans.

PMID- 12190995
TI  - PMT13, a pyrimidone analogue of thiazolidinedione improves insulin resistance
      associated disorders in animal models of type 2 diabetes.
AB  - AIM: To evaluate the antidiabetic and hypolipidaemic potential of a novel
      thiazolidinedione, PMT13, in different animal models of insulin resistance.
      METHODS: PPAR transactivation study was performed in HEK293T cells using ligand
      binding domains of PPARalpha, gamma and delta. Insulin-resistant db/db and ob/ob
      mice were treated orally with different doses of PMT13 at 0.3-10 mg/kg/day for 15
      and 14 days respectively. Zucker fa/fa rats were treated with 3 mg/kg (p.o.) dose
      of the compound. Plasma glucose, triglyceride, free fatty acid and insulin levels
      were measured. Liver glucose 6-phosphatase (G6-Ptase) and adipose lipoprotein
      lipase activity was measured in treated mice. Isolated rat aortic preparations
      preconstricted with phenylephrine were used to study the vascular relaxation
      potential of PMT13 in presence of insulin. A 28-day oral toxicity study was
      performed in Wistar rats. RESULTS: PMT13 showed similar PPARgamma activation as
      rosiglitazone, but failed to show any activity against PPARalpha or PPARdelta. In
      obese and diabetic db/db and ob/ob mice, PMT13 showed better reduction in plasma
      glucose, triglyceride and insulin levels than rosiglitazone and an improvement in
      glucose tolerance. In insulin-resistant Zucker fa/fa rat model, PMT13 treatment
      showed better reduction in plasma triglyceride, free fatty acid and insulin
      levels than that of rosiglitazone. Treated mice showed decreased G6-Ptase
      activity in liver. The LPL activity was increased in post-heparin plasma and
      epididymal fat of treated db/db mice. In an isolated, precontracted rat aortic
      preparation, PMT13 treatment significantly increased insulin-induced relaxation.
      A 28-day oral toxicity study in rats showed no treatment-related adverse effects.
      CONCLUSION: Our studies indicate that PMT13 is a potent activator of PPARgamma
      with antidiabetic, hypolipidaemic and insulin-sensitizing properties.
      Additionally, PMT13 inhibited liver G6-Ptase activity and increased lipoprotein
      lipase activity. It showed improvement in insulin-induced vasorelaxation. The
      compound also showed a good safety margin. Therefore, PMT13 can be a potential
      drug candidate for future development.

PMID- 12190997
TI  - Early vascular abnormalities and de novo nitrate tolerance in diabetes mellitus.
AB  - OBJECTIVE: The haemodynamic consequence of altered mechanical wall properties in
      diabetes can impair the compliance characteristics or pulsatile function of
      arteries before changes in calibre or peripheral resistance become evident. We
      studied the sensitivity of pulsatile and steady-state haemodynamic variables in
      identifying vascular abnormalities and assessing arterial responsiveness to
      glyceryl trinitrate (GTN) in patients with diabetes, free from clinical
      complications of the disease. METHODS: Radial artery pressure waveforms were
      recorded in 22 patients with diabetes and 22 age- and sex-matched control
      subjects, using a calibrated tonometer device. A computer-based assessment of the
      diastolic pressure decay was used to quantify changes in arterial waveform
      morphology in terms of pulsatile (arterial compliance) and steady-state
      (peripheral resistance) haemodynamics. Pressure pulse waveforms were recorded
      before and 3, 6 and 9 min after the administration of 300 micro g of GTN.
      RESULTS: Of the pulsatile and steady-state impedance parameters, only small
      artery compliance was significantly different in patients, 4.7 ml/mmHg (95% CI
      3.8-5.8), compared with control subjects 7.1 ml/mmHg (95% CI 5.4-8.7); (p <
      0.05). In response to GTN small artery compliance increased, and systemic
      vascular resistance decreased significantly in control subjects; (p < 0.05) but
      remained unchanged in patients with diabetes. CONCLUSIONS: Arterial waveform
      analysis proved more sensitive in detecting early vascular abnormalities and
      tracking the haemodynamic effects of GTN in patients with diabetes than changes
      in total peripheral resistance. The diminished responsiveness of the arterial
      vasculature to organic nitrates may have therapeutic implications for the
      treatment of cardiovascular disease in diabetes mellitus.

PMID- 12190996
TI  - The effects of miglitol on glucagon-like peptide-1 secretion and appetite
      sensations in obese type 2 diabetics.
AB  - BACKGROUND: Previous studies reported that administration of first generation
      alpha-glucosidase inhibitors (AGIs), such as voglibose or acarbose, produced
      exaggerated and sustained postprandial responses of glucagon-like peptide-1 (GLP
      1), an incretin hormone from the enteroinsular axis, in healthy humans. Little is
      known about the postprandial release of GLP-1 after AGI therapy in diabetics. GLP
      1 plays a role to mediate satiety. Any agent that substantially elevates GLP-1
      levels may theoretically reduce hunger, increase satiation and limit food intake.
      OBJECTIVES: This study was performed to analyse the effect of miglitol, a more
      potent second generation AGI with fewer gastrointestinal side-effects, on the
      regulation of meal-related GLP-1 secretion and on the change of insulin-glucose
      dynamics as well as the release of gastric inhibitory polypeptide (GIP), another
      incretin hormone, after stimulation by an ordinary meal in obese type-2-diabetic
      subjects. Miglitol's subsequent influences on appetite sensations and food intake
      were also measured. DESIGN: In total, 8 obese type-2-diabetic women were
      randomized to receive treatment with 100 mg of miglitol or placebo three times a
      day for 2 days (six doses total) in a double-blind fashion. On day 3 of each
      treatment period (miglitol or placebo), measurements of GLP-1, GIP, insulin and
      glucose were taken periodically during 3 h after eating a 720 kcal breakfast.
      Appetite ratings with visual analogue scales (VASs) were used to assess ingestive
      behaviour hourly just before breakfast and hourly after for 6 h until immediately
      before lunch. The number of tuna sandwiches eaten at lunch was used to measure
      food consumption. RESULTS: The plasma GLP-1, glucose, insulin and GIP levels in
      response to the mixed meal were compared after the miglitol and placebo
      treatment. Miglitol effectively enhanced postprandial GLP-1 release and
      suppressed plasma GIP secretion. The ingestion of a mixed meal induced a
      remarkable rise in GLP-1 after miglitol as compared with placebo in overweight
      diabetic subjects. The meal-related rise in GLP-1 after miglitol was
      significantly greater at all time-points between 30 and 180 min than after the
      placebo. The postprandial incremental area under the curve for GLP-1 with
      miglitol treatment was about twofold that with the placebo. The GLP-1 level
      reached a maximum at 120 min after the mixed meal and steadily rose throughout
      the rest of the 3-h study period. In the miglitol-treated condition, the average
      caloric intake at lunch during a 30-min eating period was 12% lower (p < 0.05) as
      compared with that after the placebo in six out of the eight subjects who
      exhibited a GLP-1 rise after the breakfast meal by greater than 30% from the
      placebo-treated condition. Correspondingly, the average rating scores were
      significantly lower for hunger feelings and markedly greater for sensations of
      satiety under the miglitol treatment; beginning 2 and 3 h, respectively, before
      the lunch test. CONCLUSIONS: Miglitol induced an enhanced and prolonged GLP-1
      release at high physiological concentrations after ingesting an ordinary meal in
      glycaemic-controlled diabetics. The excessive postprandial GLP-1 elevation after
      miglitol therapy modified feeding behaviour and food intake, and thereby has
      potential value in regulating appetite and stabilizing body weight in obese type
      2-diabetic patients.

PMID- 12190998
TI  - Expression of resistin in the adipose tissue is modulated by various factors
      including peroxisome proliferator-activated receptor alpha.
AB  - AIM: Resistin has been suggested to link obesity to diabetes by antagonizing
      insulin action. However, this model is based on limited observations and how
      resistin links the two complex processes is not known. In this study, we
      investigated the effects of various factors on the expression of resistin and
      examined the generality of the proposal. METHODS: Total RNA was isolated from the
      adipose tissues of lean, obese and peroxisome proliferator-activated receptor
      (PPAR)alpha-null mice fed a control diet or that contained a PPAR ligand, and
      analysed by Northern blotting using cDNAs for resistin, leptin, aP2 and other
      mRNAs as probes. For quantitative analysis, an image analyser was used. RESULTS:
      Basal expression of resistin mRNA was suppressed by obesity, but the extent of
      suppression differed significantly among the mouse strains and types of adipose
      tissue examined. Anti-diabetic thiazolidinediones induced resistin expression in
      the lean mice and showed smaller effects in obese mice. Furthermore, PPARalpha
      was shown to play an important role in constitutive expression of resistin in the
      adipose tissue. CONCLUSION: Our results indicated that diverse factors modulate
      the expression of resistin in the adipose tissues of mice, and suggested that
      resistin is not a master hormone linking obesity to diabetes.

PMID- 12190999
TI  - Nicotine treatment decreases food intake and body weight via a leptin-independent
      pathway in Psammomys obesus.
AB  - It has been reported previously that leptin may be involved in nicotine's ability
      to reduce body weight. Our aim was to investigate whether the anorexic action of
      nicotine is related to the actions of leptin by utilizing lean leptin-sensitive
      and obese leptin-resistant Psammomys obesus. Lean and obese P. obesus were
      assigned to receive nicotine sulphate at 6, 9 or 12 mg/day or saline (control)
      for 9 days (n = 6-10 in each group), administered using mini-osmotic pumps. Food
      intake, body weight, plasma leptin concentrations, plasma insulin and blood
      glucose were measured at baseline and throughout the study period. Nicotine
      treatment reduced food intake by up to 40% in lean and obese P. obesus. Plasma
      leptin levels fell significantly only in lean nicotine-treated animals, whereas
      no changes were observed in obese nicotine-treated animals. However, both lean
      and obese nicotine-treated animals had similar reductions in body weight. Our
      results show that nicotine has dramatic effects on food intake and body weight,
      however, these changes appear to be independent of the leptin signalling pathway.

PMID- 12191000
TI  - Scientific misconduct and the biomedical enterprise: a reminder.

PMID- 12191001
TI  - The predictive value of transcutaneous oxygen tension measurement in diabetic
      lower extremity ulcers treated with hyperbaric oxygen therapy: a retrospective
      analysis of 1,144 patients.
AB  - The objective of this retrospective analysis was to determine the reliability of
      transcutaneous oxygen tension measurement (TcPO2) in predicting outcomes of
      diabetics who underwent hyperbaric oxygen therapy for lower extremity wounds. Six
      hyperbaric facilities provided TcPO2 data under several possible conditions:
      breathing air, breathing oxygen at sea level, and breathing oxygen in the
      chamber. Overall, 75.6% of the patients improved after hyperbaric oxygen therapy.
      Baseline sea-level air TcPO2 identified the degree of tissue hypoxia but had
      little statistical relationship with outcome prediction because some patients
      healed after hyperbaric oxygen therapy despite very low prehyperbaric TcPO2
      values. Breathing oxygen at sea level was unreliable for predicting failure, but
      68% reliable for predicting success after hyperbaric oxygen therapy. TcPO2
      measured in chamber provides the best single discriminator between success and
      failure of hyperbaric oxygen therapy using a cutoff score of 200 mmHg. The
      reliability of in-chamber TcPO2 as an isolated measure was 74% with a positive
      predictive value of 58%. Better results can be obtained by combining information
      about sea-level air and in-chamber oxygen. A sea-level air TcPO2 < 15 mmHg
      combined with an in-chamber TcPO2 < 400 mmHg predicts failure of hyperbaric
      oxygen therapy with a reliability of 75.8% and a positive predictive value of
      73.3%.

PMID- 12191002
TI  - Maggot versus conservative debridement therapy for the treatment of pressure
      ulcers.
AB  - To define the efficacy and safety of maggot therapy, a cohort of 103 inpatients
      with 145 pressure ulcers was evaluated. Sixty-one ulcers in 50 patients received
      maggot therapy at some point during their monitored course; 84 ulcers in 70
      patients did not. Debridement and wound healing could be quantified for 43 maggot
      treated wounds and 49 conventionally treated wounds. Eighty percent of maggot
      treated wounds were completely debrided, while only 48% of wounds were completely
      debrided with conventional therapy alone (p=0.021). Within 3 weeks, maggot
      treated wounds contained one-third the necrotic tissue (p = 0.05) and twice the
      granulation tissue (p < 0.001), compared to non-maggot-treated wounds. Of the 31
      measurable maggot-treated wounds monitored initially during conventional therapy,
      necrotic tissue decreased 0.2 cm(2) per week during conventional therapy, while
      total wound area increased 1.2 cm(2) per week. During maggot therapy, necrotic
      tissue decreased 0.8 cm(2) per week (p = 0.003) and total wound surface area
      decreased 1.2 cm2 per week (p = 0.001). Maggot therapy was more effective and
      efficient in debriding chronic pressure ulcers than were the conventional
      treatments prescribed. Patients readily accepted maggot therapy, and adverse
      events were uncommon.

PMID- 12191003
TI  - Expression of preadipocyte factor-1(Pref-1), a delta-like protein, in healing
      mouse ears.
AB  - Preadipocyte factor-1 (Pref-1), a delta-like protein containing epidermal growth
      factor-repeats, is expressed in proliferating cells in a variety of tissues and
      is believed to be involved in maintaining the undifferentiated state of these
      cells. Using microarray analysis, reverse transcriptase-polymerase chain
      reaction, in-situ hybridization, and immunohistochemistry, we have identified
      Pref-1 expression in the healing ears of two strains of mice, MRL and C57BL/6.
      MRL is unusual in that ear punches completely regenerate the ear tissue along
      with new cartilage with no scarring. Pref-1 is more highly expressed in the MRL
      wounds, is uniquely found in a condensation of cells within the regenerating
      tissue of the blastema, and may contribute to the regenerative capacity of the
      MRL ear wound.

PMID- 12191004
TI  - Retroviral delivery of dominant-negative vascular endothelial growth factor
      receptor type 2 to murine wounds inhibits wound angiogenesis.
AB  - Vascular endothelial growth factor (VEGF) is a potent paracrine signal for
      initiating angiogenesis. Although VEGF can bind to several cell surface
      receptors, VEGF receptor type 2 (VEGFR2, a.k.a. KDR or flk-1) is the primary
      receptor responsible for VEGF-induced endothelial cell proliferation. To
      determine whether the VEGF-VEGFR2 signaling axis has an important role in wound
      healing angiogenesis, we used a retrovirus to deliver a signaling-defective
      truncated VEGFR2 (tm VEGFR2) to block VEGF-VEGFR2-induced endothelial cell
      proliferation in murine wounds. We show that the retroviral construct effectively
      blocked phosphorylation of VEGFR2 in vitro and we were able to express the
      truncated receptor in murine wounds. We achieved significant reduction of
      angiogenesis and granulation tissue formation in murine wounds, but this did not
      lead to delayed wound closure. In contrast, there was a corresponding increase in
      wound contraction, showing that functional VEGFR2 intracellular signaling is not
      critical for normal closure of excisional dermal wounds. Our results show a novel
      relationship between wound bed vascularity and wound contraction.

PMID- 12191005
TI  - Molecular and cell biology of porcine HSP47 during wound healing: complete cDNA
      sequence and regulation of gene expression.
AB  - Heat shock protein (HSP) 47 is a major stress-inducible protein that is localized
      to the endoplasmic reticulum of avian and mammalian cells and is thought to act
      as a molecular chaperone specific for the processing of procollagen. However,
      limited information is available regarding the regulation of HSP47 during wound
      healing. Using a polymerase chain reaction strategy, screening of a cDNA library,
      and RACE-polymerase chain reaction approaches, the sequence of a full-length
      porcine HSP47 cDNA has been identified. The cDNA contained 2096 bp that encodes
      for an 18 amino acid signal peptide and a mature protein coding region consisting
      of 401 amino acid residues. It also included 108 bp of the 5' noncoding region
      and a 731-bp 3' noncoding region. The deduced amino acid is 83% identical to
      chicken, 87% identical to mouse, 88% identical to rat, and 91% identical to human
      HSP47. It also shares between 26% and 30% identity with different members of the
      serine protease inhibitor superfamily. The protein contains a RDEL endoplasmic
      reticulum retention signal, and two potential glycosylation sites. All of these
      features are characteristic of HSP47 in higher vertebrates. Heat shock treatment
      of porcine fibroblasts led to up-regulation of HSP47 at both the transcriptional
      and translational levels. HSP47 protein levels were also up-regulated during skin
      wound healing in a pig model. Moreover, a higher molecular weight complex at
      approximately 140 Kda containing HSP47 was detected at the stage of healing that
      was coincident with the maximal transcriptional expression of HSP47 during wound
      healing in this animal model. Further investigation of how HSP47 is regulated
      during normal and abnormal skin wound healing may lead to new therapeutic
      approaches to improve the healing process.

PMID- 12191006
TI  - Morphologic examination of CD3-CD4(bright) cells in rat liver.
AB  - Recently, we found CD3-CD4(bright) cells with comparative specificity for normal
      rat liver. In the current study, we investigated the type and form of both CD3
      CD4(bright) cells and CD3-CD4(dull) cells in the rat liver. The surface phenotype
      of hepatic mononuclear cells in Lewis rats was identified by using monoclonal
      antibodies including anti-CD4, anti-CD3, and antimacrophage in conjunction with
      two- or three-color immunofluorescence analysis. CD3-CD4(bright) cells and CD3
      CD4(dull) cells were examined morphologically using May-Giemsa staining and
      scanning electron microscopy. The distribution of CD3-CD4(bright) cells and CD3
      CD4(dull) cells 48 hours after intravenous administration of liposome
      encapsulated dichloromethylene diphosphate was also investigated. In comparison
      to CD3-CD4(dull) cells, CD3-CD4(bright) cells were slightly larger macrophages
      with abundant cytoplasmic granules, being present with comparative specificity
      for normal rat liver and showing negligible effects by intravenous liposome
      encapsulated dichloromethylene diphosphate administration. These data suggest
      that in normal young rat liver these CD3-CD4(dull) and CD3-CD4(bright) cells may
      be dendritic cells and Kupffer cells that shift from the liver to the spleen or
      vice versa. These cells may also be able to locally proliferate in liver or
      spleen due to changes in the developing liver.

PMID- 12191007
TI  - Angiogenesis induction and regression in human surgical wounds.
AB  - Angiogenesis in human wound healing is not well characterized, with only sparse
      information available regarding the maturation and fate of vessels formed as a
      consequence of human tissue repair. Therefore, this study aimed to establish the
      temporal profile of angiogenesis in human dermal wounds. Punch biopsies were
      obtained under local anesthesia from 45 patients following breast surgery. Scars
      were predominantly between 2 and 52 weeks after surgery but in five patients were
      > 52 weeks. Control samples were taken from breast skin peroperatively (n = 24).
      Quantification of vascular density was performed using the Chalkley grid,
      following antibody staining for platelet endothelial cell adhesion molecule.
      Vascular patterns, wound cellularity and morphology were also determined.
      Cumulative microvessel density was increased in all samples when compared to
      controls (p < 0.05). This was greatest 2 to 24 weeks following surgery 17 (15-21)
      median (range), decreased thereafter, but remained elevated compared to controls
      even in the mature scars > 52 weeks. Control tissue showed an ordered
      morphological arrangement of dermal structures, collagen, and elastic fibers.
      However, wounding resulted in marked structural distortion for up to 15 weeks. In
      conclusion, this study shows for the first time the prolonged persistence of both
      microvessels and cellularity (fibroblastic cells), in addition to structural
      distortion in human dermal wounds, which is in contrast to previous in vitro and
      in vivo studies.

PMID- 12191011
TI  - Plants: cellular systems rooted in place.

PMID- 12191008
TI  - Transforming growth factor-beta2 (TGF-beta2) reverses the inhibitory effects of
      fibrin sealant on cutaneous wound repair in the pig.
AB  - Tensile strength of 2-cm, full-thickness, surgically incised porcine skin wounds
      sealed with fibrin sealant was enhanced compared to conventionally sutured wounds
      at 6 hours postwounding, but was significantly reduced after 3 days.
      Supplementation of fibrin sealant with transforming growth factor-beta2 (TGF
      beta2) reversed the inhibitory effects of fibrin sealant on tensile strength at 3
      days, and enhanced tensile strength at 7 days compared to suture or fibrin
      sealant alone. By 14 days, the tensile strengths of all wounds were similar,
      although wounds treated with fibrin sealant supplemented with TGF-beta2 showed a
      small, but statistically significant, improvement in wound strength compared to
      wounds treated with fibrin sealant alone. Histological assessment at day 7
      revealed significant remnants of fibrin sealant at the wound site following
      fibrin sealant treatment alone, while wounds treated with fibrin sealant
      supplemented with TGF-beta2 or suture exhibited fibroblast infiltration and
      extracellular matrix deposition. At day 7, TGF-beta was immunolocalized in the
      base and margins of only wounds treated with fibrin sealant supplemented with TGF
      beta2. A significant increase in matrix metalloproteinase-9 activity was found in
      fibrin sealant-treated wounds at day 7 as compared to sutured wounds. Addition of
      TGF-beta to the fibrin sealant suppressed the up-regulation of matrix
      metalloproteinase-9 in these wounds. These results suggest that fibrin sealant
      supplemented with TGF-beta may provide superior wound healing as compared to
      fibrin sealant alone.

PMID- 12191009
TI  - Contractile actin expression in torn human menisci.
AB  - The human meniscus is subject to injury that necessitates repair or removal. Many
      aspects of the cellular response to injury have not been well characterized. The
      purpose of this study was to describe the cellular distributions within the torn
      human meniscus. In addition to evaluating the cell density in selected regions,
      we investigated the cellular expression of a contractile actin isoform that has
      recently been found in the intact human meniscus. Included as a contemporaneous
      comparative group were torn human meniscal allografts. We hypothesized that a
      hypercellular surface zone would be found in the torn menisci, with a higher
      percentage of cells in this peripheral region expressing alpha-smooth muscle
      actin compared with other locations in the interior of the remnant. The rationale
      for this hypothesis was based on prior immunohistochemical investigations of the
      distribution of alpha-smooth muscle actin-containing cells in the torn human
      anterior cruciate ligament. Eighteen torn meniscal specimens were obtained from
      17 patients, 0.5 to 84 months after injury, and four torn allograft meniscal
      samples were retrieved from three patients, 11 to 49 months after implantation.
      Microtomed sections of paraffin-embedded tissue were stained with hematoxylin and
      eosin and a monoclonal antibody to alpha-smooth muscle actin. The cell density
      and percentage of cells containing alpha-smooth muscle actin were determined in
      the following zones: synovial, vascular, hypercellular with loose collagen,
      hypocellular with dense collagen, and organized collagen. A cellular layer that
      resembled synovium was present on the surface of all but two of the specimens.
      Vascular regions were often continuous with the synovium abutting the more
      interior loose collagen zones. The total cell density was greatest in each of the
      zones closest to the periphery (synovium, vascular, and loose collagen; p <
      0.001), when compared to the interior of the tissue. The synovium-like layer was
      found to have the highest percentage of alpha-smooth muscle actin-expressing
      cells and the highest alpha-smooth muscle actin-containing cell density (p <
      0.05). Similar results were found for the torn allograft menisci. These findings
      confirm the working hypothesis and suggest that the torn human meniscus is
      capable of mounting a reparative response, including the proliferation of cells
      capable of contributing to wound closure. This underscores the importance of
      providing a bridging scaffold into which such cells can migrate.

PMID- 12191012
TI  - Protein secretion in plants: from the trans-Golgi network to the outer space.
AB  - Functional analysis of exocytosis in yeast and animal cells has led to the
      identification of conserved elements and mechanisms of the trafficking machinery
      over the last decade. Although functional studies of protein secretion in plants
      are still fairly limited, the Arabidopsis genome sequence provides an opportunity
      to identify key players of vesicle trafficking that are conserved across the
      eukaryotic kingdoms. Here, we review and add to recent genome analyses of
      trafficking components and highlight some plant-specific modifications of the
      common eukaryotic machinery. Furthermore, we discuss the evidence for targeted,
      polarised secretion in plant cells, and speculate about possible underlying cargo
      sorting processes at the trans-Golgi network and endosomes, based on what is
      known in animals and yeast.

PMID- 12191013
TI  - Clathrin and plant endocytosis.
AB  - Endocytosis requires the coordinated interaction of a plethora of cytosolic and
      membrane proteins. In mammalian cells, clathrin plays a crucial role in this
      process as a scaffolding protein underlying the invaginating plasma membrane and
      surrounding the primary endocytic vesicle. Despite great similarities at the
      morphological level, the cargo of endocytic clathrin-coated vesicles in plant
      cells remains to be elucidated. Thus, the role of endocytosis in the plant cell
      is difficult to ascertain. This review will present important discoveries on
      putative endosomal compartments and on the functions of plasma membrane-derived
      plant clathrin-coated vesicles, but will also emphasize the striking similarities
      of the clathrin-, network- and vesicle fusion-machineries between plant and
      animal cells.

PMID- 12191014
TI  - Membrane trafficking during plant cytokinesis.
AB  - Plant morphogenesis is regulated by cell division and expansion. Cytokinesis, the
      final stage of cell division, culminates in the construction of the cell plate, a
      unique cytokinetic membranous organelle that is assembled across the inside of
      the dividing cell. Both during cell-plate formation and cell expansion, the
      secretory pathway is highly active and is polarized toward the plane of division
      or toward the plasma membrane, respectively. In this review, we discuss results
      from recent genetic and biochemical research directed toward understanding the
      molecular events occurring during cytokinesis and cell expansion, including data
      supporting the idea that during cytokinesis one or more exocytic pathways are
      polarized toward the division plane. We will also highlight recent evidence for
      the roles of secretory vesicle transport and cytoskeletal machinery in cell-plate
      membrane trafficking and fusion.

PMID- 12191015
TI  - Identification of RanBP2- and kinesin-mediated transport pathways with restricted
      neuronal and subcellular localization.
AB  - Ran-binding proteins, karyopherins, and RanGTPase mediate and impart
      directionality to nucleocytoplasmic transport processes. This biological process
      remains elusive in neurons. RanBP2 has been localized at the nuclear pore
      complexes and is very abundant in the neuroretina. RanBP2 mediates the assembly
      of a large complex comprising RanGTPase, CRM1/exportin-1, importin-beta, KIF5
      motor proteins, components of the 19S cap of the 26S proteasome, ubc9 and opsin.
      Here, we show RanBP2 is abundant in the ellipsoid compartment of photoreceptors
      and RanGTPase-positive particles in cytoplasmic tracks extending away from the
      nuclear envelope of subpopulations of ganglion cells, suggesting RanBP2's release
      from nuclear pore complexes. KIF5C and KIF5B are specifically expressed in a
      subset of neuroretinal cells and differentially localize with RanBP2 and importin
      beta in distinct compartments. The C-terminal domains of KIF5B and KIF5C, but not
      KIF5A, associate directly with importin-beta in a RanGTPase-dependent fashion in
      vivo and in vitro, indicating importin-beta is an endogenous cargo for a subset
      of KIF5s in retinal neurons. The KIF5 transport pathway is absent from the myoid
      region of a topographically distinct subclass of blue cones and the distribution
      of kinesin-light chains is largely distinct from its KIF5 partners. Altogether,
      the results identify the existence of neuronal- and subtype-specific kinesin
      mediated transport pathways of importin-beta-bound cargoes to and/or from RanBP2
      and indicate RanBP2 itself may also constitute a scaffold carrier for some of its
      associated partners. The implications of these findings in protein kinesis and
      pathogenesis of degenerative neuropathies are discussed.

PMID- 12191016
TI  - Cycling of early Golgi proteins via the cell surface and endosomes upon lumenal
      pH disruption.
AB  - The cis-Golgi protein GPP130 reversibly redistributes to endosomes upon pH
      disruption, but the identity of the endosomes and the involved cycling route are
      unknown. It is also unknown whether any other early Golgi proteins participate in
      this pathway. Here, we analyze GPP130 and the structurally related Golgi protein
      GP73. Unlike the TGN marker TGN38/46, GPP130 and GP73 colocalized in the early
      Golgi and redistributed to the ER after brefeldin A treatment. Nevertheless,
      after pH disruption by monensin, GPP130 and GP73 redistributed to endosomes
      containing redistributed TGN38/46, but not other endosomal markers. In common
      with TGN38/46, the redistribution involved transient appearance on the plasma
      membrane, and upon monensin washout, the proteins moved back to the Golgi along a
      microtubule- and PI3 kinase-independent route. Although GP73 did not associate
      with GPP130, its steady-state Golgi targeting was also mediated by a lumenal
      predicted coiled-coil stem domain. These findings indicate that at least two
      early Golgi proteins, each containing stem domain Golgi targeting determinants,
      cycle to the cell surface and back along the late endosome independent TGN38/46
      pathway.

PMID- 12191017
TI  - The lumenal domain of the integral membrane protein phogrin mediates targeting to
      secretory granules.
AB  - Phogrin, a transmembrane glycoprotein of neuroendocrine cells, is localized to
      dense-core secretory granules. We have investigated the subcellular targeting of
      phogrin by analyzing the sorting of a series of deletion mutants to the regulated
      pathway of secretion in AtT20 cells. The lumenal domain as a soluble protein was
      efficiently routed to granules, based on a combination of morphological analysis
      and secretion studies. Sorting was not dependent on a candidate targeting signal
      consisting of an N-terminal conserved cysteine-rich motif. Both the pro-region
      and the lumenal domain of mature, post-translationally processed phogrin
      independently reached the granule, although the pro-region was sorted more
      efficiently. Once within the regulated secretory pathway, all phogrin lumenal
      domain proteins were stored in functional granules for extended periods of time.
      Thus, phogrin possesses several domains contributing to its targeting to the
      secretory granule. Our findings support a model of granule biogenesis where
      proteins are sorted on the basis of their biochemical properties rather than via
      signal-dependent binding to a targeting receptor. Sorting of integral membrane
      proteins mediated by the lumenal domain may ensure that functionally important
      transmembrane molecules are included in the forming granule.

PMID- 12191018
TI  - Pallidin is a component of a multi-protein complex involved in the biogenesis of
      lysosome-related organelles.
AB  - The Hermansky-Pudlak syndrome defines a group of genetic disorders characterized
      by defective lysosome-related organelles such as melanosomes and platelet dense
      bodies. Hermansky-Pudlak syndrome can be caused by mutations of at least four
      genes in humans and 15 genes in mice. One of these genes is mutated in the pallid
      mouse strain and encodes a novel protein named pallidin (L. Huang, Y. M. Kuo and
      J. Gitschier, Nat Genet 1999; 23: 329-332). Pallidin has no homology to any other
      known protein and no recognizable functional motifs. We have conducted a
      biochemical characterization of human pallidin using a newly developed polyclonal
      antibody. We show that pallidin is a ubiquitously expressed approximately 25 kDa
      protein found both in the cytosol and peripherally associated to membranes.
      Sedimentation velocity analyses show that native pallidin has a sedimentation
      coefficient of approximately 5.1 S, much larger than expected from the molecular
      mass of the pallidin polypeptide. In line with this observation, cosedimentation
      and coprecipitation analyses reveal that pallidin is part of a hetero-oligomeric
      complex. One of the subunits of this complex is the product of another Hermansky
      Pudlak syndrome gene, muted. Fibroblasts derived from the muted mouse strain
      exhibit reduced levels of pallidin, suggesting that the absence of the muted
      protein destabilizes pallidin. These observations indicate that pallidin is a
      subunit of a novel multi-protein complex involved in the biogenesis of lysosome
      related organelles.

PMID- 12191019
TI  - The melanocytic protein Melan-A/MART-1 has a subcellular localization distinct
      from typical melanosomal proteins.
AB  - To delineate the role of the melanocyte lineage-specific protein Melan-A/MART-1
      in melanogenic functions, a set of biochemical and microscopical studies was
      performed. Biochemical analysis revealed that Melan-A/MART-1 is post
      translationally acylated and undergoes a rapid turnover in a pigmented melanoma
      cell line. Immunofluorescence and immunoelectron microscopy analyses indicated
      that Melan-A/MART-1 is mainly located in the Golgi area and only partially
      colocalizes with melanosomal proteins. Quantitative immunoelectron microscopy
      showed that the highest proportion of the cellular content of Melan-A/MART-1 was
      found in small vesicles and tubules throughout the cell, whereas the
      concentration was maximal in the Golgi region, particularly the trans-Golgi
      network. Substantial labeling was also present on melanosomes, endosomes, ER,
      nuclear envelope, and plasma membrane. In early endosomes, Melan-A was enriched
      in areas of the limiting membrane covered by a bi-layered coat, a structural
      characteristic of melanosomal precursor compartments. Upon melanosome maturation,
      Melan-A concentration decreased and its predominant localization shifted from the
      limiting membrane to internal vesicle membranes. In conjunction with its
      acylation, the high expression levels of Melan-A in the trans-Golgi network, in
      dispersed vesicles, and on the limiting membrane of premelanosomes indicate that
      the protein may play a role during the early stage of melanosome biogenesis.

PMID- 12191021
TI  - Dialysis therapies for end-stage renal disease.
AB  - End-stage renal disease (ESRD) has various causes that may differ according to
      country and racial group. Whatever the cause, unless the water, salt,
      electrolytes, and waste products excreted by normal kidneys are removed, their
      accumulation will result in death. Removal of these products can be variably
      achieved by either hemodialysis or peritoneal dialysis. The principles and
      outcomes of these techniques are described, as are their complications. It is
      important that these two different methods of treatment are not regarded as
      competitive, but are integrated, together with renal transplantation where
      appropriate, into the management of patients with ESRD to optimize both outcome
      and quality of life.

PMID- 12191022
TI  - The pathology of dialysis.
AB  - There are a number of pathologies that are associated with the development of
      renal failure. Once renal function has deteriorated beyond a point where life is
      not sustainable without dialysis, new sets of pathologic processes develop. These
      are, in part, related to the continuation of poor renal function and to the
      process of dialysis itself. This article addresses the processes that are
      believed to be due to dialysis, among which are disorders of bone, deposition of
      metals and amyloid within a number of tissues, and local problems such as
      inflammation and tumors related to the dialysis site.

PMID- 12191023
TI  - Contrast agents in patients on dialysis.
AB  - Contrast media are used to enhance the structural and functional information that
      is provided by imaging methods. They are used particularly in conventional
      radiographic (X-ray) investigations, but are also used in magnetic resonance
      imaging (MRI) and increasingly in ultrasound (US). The water-soluble, iodinated,
      intravascular radiographic agents are commonly used, and in large doses. They are
      excreted almost exclusively by the kidney and may have nephrotoxic effects. The
      use of these agents in patients with renal impairment may potentially be
      problematic. In this article the chemical composition and pharmacokinetics of
      these contrast agents are reviewed, as are their potentially toxic effects on the
      heart, neural tissues, kidney, and endothelium. Their safety for use in the
      patient with end-stage renal disease (ESRD) and those on dialysis is discussed.
      This aspect is also addressed briefly for the contrast agents used to augment MRI
      and US.

PMID- 12191024
TI  - Renal imaging in patients requiring renal replacement therapy.
AB  - Recent advances in imaging technology and interventional radiologic procedures
      have resulted in an increased variety of radiological techniques that can be used
      to assess patients who present with renal failure and require renal replacement
      therapy. This chapter provides an overview of the relative strengths and
      weaknesses of the available imaging methods. In particular, it covers the
      expanding role of the cross-sectional, noninvasive, multiplanar imaging
      techniques such as gray-scale and Doppler ultrasound, magnetic resonance imaging
      (MRI) and angiography (MRA), and nonenhanced helical or multislice computed
      tomography (CT). These imaging methods are increasingly replacing those used in
      the past, such as the conventional radiographic urogram, which requires a high
      dose of intravenous contrast media, and digital subtraction arteriography. The
      chapter also covers the radiologic investigation of complications of acquired
      renal cystic disease, including renal cell carcinoma, hemorrhage, cyst infection
      and rupture, and nephrolithiasis.

PMID- 12191025
TI  - Image-guided peritoneal access and management of complications in peritoneal
      dialysis.
AB  - The principal complications of continuous ambulatory peritoneal dialysis (CAPD),
      namely malposition of the dialysis catheter, peritonitis, exit site infection,
      leakage of dialysis fluid, sclerosing peritonitis, and renal cysts and tumors,
      are considered in this article. The techniques that are used to reposition
      displaced dialysis catheters and extend the duration of dialysis are described.
      The role of imaging in establishing the diagnosis of peritonitis is relatively
      small. However, both computed tomography (CT) and ultrasound may be used to
      identify loculation of fluid and localized sites of sepsis, and permit
      percutaneous drainage. Ultrasonography of the catheter track through the
      percutaneous tissues allows identification of pericatheter collections in
      patients with exit-site infection. The technique of CT peritoneography is helpful
      in establishing sites of dialysis fluid leakage. These commonly occur at the site
      of entry of the dialysis catheter, through abdominal incisions, or along the
      patent tunica vaginalis into the scrotum. The appearances on CT of sclerosing
      peritonitis reflect pathologic changes and are characterized by the presence of
      peritoneal thickening and calcification. Bowel obstruction, which may develop in
      sclerosing peritonitis, can be identified on abdominal radiographs or barium
      studies of the gastrointestinal tract. Acquired renal cystic disease and renal
      carcinomas occur in a significant proportion of patients undergoing CAPD.
      Ultrasound is the investigation of first choice in the identification and
      clarification of the pathology (cystic or solid) of suspected renal masses.

PMID- 12191026
TI  - The role of vascular radiology in hemodialysis access.
AB  - The article summarizes the role of vascular radiology in the imaging and salvage
      of hemodialysis fistulas and in the placement and maintenance of tunneled
      dialysis access catheters.

PMID- 12191027
TI  - Nuclear medicine studies in the dialysis patient.
AB  - Nuclear medicine (scintigraphy) studies that are performed in patients being
      prepared for regular dialysis treatment include the measurement of renal
      clearance and dynamic studies of renal perfusion and function. Static
      scintigraphy with 99mTc-DMSA may be used in the evaluation of children at risk of
      renal damage and further functional deterioration. In patients on peritoneal
      dialysis, nuclear medicine procedures enable the diagnosis of structural
      complications such as intra-abdominal herniations and leaks. Diagnosis of
      infections of the vascular access sites in patients on hemodialysis and of the
      catheter tunnel in patients on peritoneal dialysis can be made with high
      diagnostic accuracy using radiolabeled, autologous leukocytes. Scintigraphy is
      valuable in delineating the extent of deposits of amyloid and parenchymal
      microcalcifications, and may be helpful in the functional evaluation of organs
      and tissues involved in the pathophysiology of renal impairment and dialysis. If
      radioiodine therapy with 131I is performed in patients on hemodialysis with
      benign or malignant thyroid disease, then pretherapeutic dosimetry is necessary
      to avoid over- and undertreatment. Radioiodine therapy in the dialysis patient
      leads to only insignificant contamination of dialysis equipment and marginal
      exposure to the medical staff.

PMID- 12191028
TI  - Imaging in dialysis spondyloarthropathy.
AB  - Destructive spondyloarthropathy has recently been described in patients who
      undergo maintenance hemodialysis for chronic renal disease. The condition most
      frequently involves the lower segment of the cervical spine, although the
      craniocervical junction also may be affected. Although the pathogenesis of
      destructive spondyloarthropathy remains unclear, the disorder is thought to
      relate to a hemodialysis-associated amyloidosis. It appears that the disease
      correlates with the duration of hemodialysis, although it has been reported in
      patients with chronic renal insufficiency not associated with hemodialysis.
      Radiographic features simulate those of an infectious process, encompassing a
      range of abnormalities from superficial erosions to large bony defects. Computed
      tomography (CT) images reveal osteolytic areas, with bone sclerosis of adjacent
      vertebral endplates, and minimal osteophytosis. The intervertebral spaces appear
      narrow or obliterated. On magnetic resonance imaging (MRI), the disorder may show
      the imaging characteristics of spondylodiskitis. The absence of high signal
      intensity on T2-weighted images generally helps to eliminate the diagnosis of an
      infection. With progression of the disease, collapse of a vertebral body and
      spinal instability may occur. Severe complications of destructive
      spondyloarthropathy in long-term dialysis patients may include spinal cord
      compromise, necessitating surgical decompression, with or without spinal
      stabilization.

PMID- 12191031
TI  - Breast cancer patients' satisfaction with a spontaneous system of check-up visits
      to a specialist nurse.
AB  - AIM: To describe breast cancer patients' satisfaction with a spontaneous system
      of check-up visits to a specialist nurse. BACKGROUND: There is little evidence
      that routine follow-up visits after breast cancer surgery influence survival or
      patient satisfaction. Consequently, there is a need to evaluate alternative
      follow-up programmes. SAMPLE: A strategic sample of 19 breast cancer patients,
      who were not involved in a routine follow-up system but who had the possibility
      of contacting a specialist nurse when necessary, were interviewed. METHOD: A
      qualitative descriptive design inspired by the method of phenomenographic
      analysis was used. FINDINGS: Five description categories and 606 statements
      showing similarities and differences in conceptions were obtained. The patients
      satisfaction with the knowledgeable and professional skills of the nurses was
      high. Confirmation and trust were important and necessary in order for the women
      with breast cancer to feel secure. Patients had a need for information and self
      care education. Accessibility and early assessment by professional personnel or
      an oncology nurse were essential in a system without routine follow-ups.
      DISCUSSION: This study identifies key issues in a specialist nurse-led check-up
      system. The findings can be used for developing an education programme for women
      who have undergone breast cancer surgery. Additionally, the findings emphasize
      the need to introduce more flexible solutions to the follow-up programmes, one
      alternative being specialist nurse-led check-ups.

PMID- 12191032
TI  - Breast cancer and experiences of social support. In-depth interviews of 10 women
      with newly diagnosed breast cancer.
AB  - The present study aimed to describe how 10 Norwegian women with newly diagnosed
      breast cancer experienced living with the disease. A qualitative method based on
      principles in Grounded Theory was used. Data were collected through in-depth
      interviews. This paper explores the experience of social support as it evolves in
      women's relationships with others. Social support contains emotional, practical
      and informative dimensions. Here relationships are called interactions.
      Interaction can be divided into two groups. Interactions with close relatives and
      others the women know and have contact with. Interactions with organizations and
      institution staff. These interactions consist of social support and lack of
      social support. Health professionals can assist women and their families in this
      life-threatening situation, by increasing their awareness of social support
      issues.

PMID- 12191033
TI  - 'From victim to agent': the clinical and social significance of self-help group
      participation for people with life-threatening diseases.
AB  - AIM: The main objective of the paper is to discuss the ways in which self-help
      groups can be useful to persons with life-threatening diseases like cancer or
      human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS). The
      paper offers an outline of the central characteristics of self-help groups,
      highlighted by the participants themselves. BACKGROUND: Self-help groups are a
      growing phenomenon across national borders. New empirical sociological studies
      show that nurses have become important agents in self-help groups, both within
      and outside the public health-care system. However, research on self-help groups
      is a relatively new area within nursing studies yet it serves an important
      function in shedding light on a rather unique form of social practice organized
      and managed partly by the participants themselves. METHODS: Qualitative
      interviews designed to examine how participants evaluate their experiences with
      self-help groups. The study includes 53 self-help group participants suffering
      from cancer or HIV/AIDS. FINDINGS: Contact with other people, forming of
      friendships, new networks and increased self-confidence are some of the effects
      indicated by the participants. Participation in a self-help group has a positive
      impact on the patients' ability to cope with the psychological and social
      consequences of living with a life-threatening disease. CONCLUSIONS: It is
      evident that the positive effects of self-help groups are mainly because of their
      inherent capacity for universalizing personal problems, which, in itself,
      legitimizes the scientific relevance of self-help groups. There is no evidence to
      indicate that self-help groups have a positive influence on the life expectancy
      of participants who suffer from cancer or HIV/AIDS, but it should be noted that
      this is not the explicit concern when groups are formed. By their very existence
      self-help groups indicate the need for a reevaluation of the scope and focus of
      the individualized care and nursing. The clinical and social significance of self
      help group participation has not been sufficiently accounted for.

PMID- 12191034
TI  - Life experience of Taiwanese adolescents with cancer.
AB  - This grounded theory study aimed to develop a conceptual framework of the life
      experience of Taiwanese adolescents with cancer. Sixteen adolescents (nine males
      and seven females) with cancer at all stages of the illness (i.e. diagnosis
      through terminal stage) were interviewed. Data were collected through in-depth
      interview with patients and primary caregiver, observations, medical chart
      reviews, nurses' notes, and researcher's reflexive journals. An unsettled state
      of mind emerged as the core category representing the life experience of
      adolescents with cancer. This multifaceted, dynamic process was elicited by the
      diagnosis of cancer or a change in clinical status. Five distinct subcategories
      of the life experience, in order of importance reported by participants emerged:
      physical and psychological, cognitive, social and future orientation aspects.

PMID- 12191035
TI  - Advanced home care for cancer patients at the end of life: a qualitative study of
      hopes and expectations of family caregivers.
AB  - It is increasingly common that cancer patients are cared for at home at the end
      of life, with help from advanced home care teams. This may have positive
      implications for cancer patients and their families, but it may also be
      burdensome to the family caregivers with implications for their health and well
      being. This qualitative study was therefore initiated to prospectively explore
      how family caregivers reason about their expectations of providing end-of-life
      care at home for relatives with cancer, enrolled in advanced palliative home care
      units. Ten interviews were conducted with 11 family caregivers at enrollment to
      the home care unit. A form of constant comparative analysis was used to generate
      two main themes from the data. One theme concerned the role transition into
      becoming a family caregiver, whereas the other theme relates to the transition to
      a new life situation of the caregiver (him/herself). The family caregivers
      describe themselves as the persons primarily bearing responsibility and providing
      care for their dying relatives. They were found to have many concerns about their
      own situation, especially in regard to issues temporally after the death of the
      patient, but seemed to have few expected sources of support related to these
      concerns. Professional support is described as expected primarily for care
      related tasks, although hopes may be expressed about support in other areas. The
      distinction between resources described as existing in theory and those used in
      practice also are apparent in analysis of the interviews. If home care is to be a
      positive alternative to hospital care, individual expectations should be
      considered when planning supportive care.

PMID- 12191036
TI  - Significant others' experience of suffering when living with women with breast
      cancer.
AB  - This is an inquiry into how significant others experience being close to a woman
      suffering from breast cancer. In order to find this out, theme interviews were
      arranged with 17 women and 16 significant others from four different caring
      cultures in Sweden and Finland. A phenomenological case study methodology was
      adopted and in the analysis of the data a scientific teamwork model was employed,
      based on ideas developed at the Vancouver School of Doing Phenomenology. The
      findings show that the significant others experience deep often unrelieved
      suffering. They consider themselves prisoners of a situation of uncertainty and
      powerlessness when standing by the woman. They are torn between their own
      suffering and their desire to alleviate the woman's suffering. A vicious circle
      of mutual protection intensifies the suffering of the significant other, while
      actively sharing the suffering brings relief. The gravity of the situation
      creates an ethical urge in the significant other to assume responsibility for
      life in common with the woman.

PMID- 12191038
TI  - Indwelling catheter treatment and health-related quality of life in men with
      prostate cancer in comparison with men with benign prostatic hyperplasia.
AB  - Experiences from indwelling urinary catheter treatment periods were studied.
      Little is known of what is felt from a male perspective although catheter
      treatment is a common pre- and postoperative measure for men with prostate cancer
      and benign prostatic hyperplasia (BPH). Also studied were health-related quality
      of life (HRQOL) and sense of coherence (SOC). Men with catheter experience
      (prostate cancer n = 71, BPH n = 37) were selected from a larger questionnaire
      study. Assessment was made with study-specific questions together with the QLQ C
      30 assessing HRQOL and the SOC questionnaire measuring sense of coherence. Data
      reduction method was applied to study specific variables to determine problem
      patterns. Correlation between HRQOL and SOC was determined. Results showed
      similar problem patterns in men with prostate cancer and BPH: discomfort in
      wearing catheter (e.g. uneasiness 48.2%), practical and psychosocial difficulties
      in handling and wearing catheter (e.g. attaching catheter 32.4%) and discomfort
      at installation (e.g. pain 29.7%). There was lack of knowledge about wearing and
      practical handling of the catheter. Having a cancer diagnosis did not add to
      uneasiness or practical problems. Life quality was correlated to SOC (p <or=
      0.001).

PMID- 12191037
TI  - Cancer and faith. Having faith--does it make a difference among patients and
      their informal carers?
AB  - This research considers the impact of having a religious faith on the cancer
      experience of patients and informal carers, focusing primarily on the association
      between faith and psychosocial needs. A questionnaire survey of 1000 patients in
      the north-west of England returned 402 completed questionnaires; around two
      thirds of patients indicated they had an informal carer. Using logistic
      regression analysis, we examine the relationship between the importance of 48
      needs and faith for 189 paired patients and carers, while controlling for the
      effect of eight socio-demographic and clinical variables. Patients with expressed
      faith identified fewer psychosocial needs than those without faith. In contrast,
      carers with expressed faith identified more needs than those without faith in
      relation to support from family and neighbours. Carers also needed more help with
      finding a sense of purpose and meaning, and help in dealing with
      unpredictability. Not surprisingly, both patients and carers with faith
      identified a greater need for opportunities for personal prayer, support from
      people of their own faith and support from a spiritual adviser. Various
      explanations of these differences between patients and carers are proposed. The
      crucial point is that one should not too readily assume that the cancer
      experience is shared in the same way by patients and carers. In understanding the
      faith dimension, one needs to consider both the spiritual and secular aspects of
      having a religious faith.

PMID- 12191039
TI  - Burnout among people working with intellectually disabled persons: a theory
      update and an example.
AB  - The paper offers an overview of the burnout literature connected to work stress
      and is specially aimed at professionals with responsibilities for persons with
      intellectual disabilities. In the paper different important key concepts in the
      burnout literature are both discussed in general terms, and also connected to the
      different instruments used to assess burnout. The effect of stress and burnout
      intervention procedures is also discussed thoroughly. At the end of the paper
      there is an example of an intervention study among staff working with persons
      with intellectual disabilities. The paper concludes that future progress is to be
      dependent onempirical tests of theory-based models using research designs that
      permit causal inferences. In addition there is a growing need for longitudinal
      designs reporting effects of different intervention approaches, especially among
      the staff working with persons with intellectual disabilities.

PMID- 12191040
TI  - Implementing assertive community care for patients with schizophrenia. A case
      study of co-operation and collaboration between mental health care and social
      services.
AB  - The aim of this study was to describe the personal experiences of collaboration
      and co-operation between staff from the community mental health and social
      services programmes in their daily work with schizophrenic patients. An
      additional aim was to generate the first step in a theory of how staff in the
      field of health care and social services manages to integrate their efforts on an
      individual and organizational level. The study group consisted of five members of
      a multidisciplinary team who had been working for 2 years with assertive outreach
      intensive clinical case management. Verbatim-transcribed thematic interviews were
      analysed according to the comparative method for grounded theory. The analysis
      was focused on quality of interpersonal interaction between practitioners,
      representing different professions in community-based mental health care, as well
      as the professional relationship to the patients/clients and their relatives. In
      the light of an individual and organizational perspective, different typologies
      of interpersonal interactions appeared. Three main variables were identified:
      collaborative relationship, co-operative partnership and professional-amateurism.
      Our findings on these qualitative differences in interpersonal relations should
      be taken into account in the continuing reorganization of the community health
      care services. This knowledge can also help in overcoming barriers between
      patients, professionals and organizations in the mental health services.

PMID- 12191041
TI  - Medicate, restrain or seclude? Strategies for dealing with violent and
      threatening behaviour in a Norwegian university psychiatric hospital.
AB  - The aim of this study was to examine staff strategies for applying emergency
      procedures with patients who were violent or threatening. The study addressed
      those situations where verbal intervention, voluntary medication, and other
      interventions had been tried unsuccessfully and where staff found it necessary to
      apply emergency procedures in the shape of forced emergency medication
      (pharmacological restraint), physical restraint, and seclusion. The study was
      conducted in a 100-bed Norwegian university psychiatric hospital. By
      retrospectively examining hospital records we found there were 797 episodes of
      physical restraint, 384 episodes of pharmacological restraint, and 88 episodes of
      seclusion during a five and a half year period. The preferred emergency
      procedures varied significantly with patients' sex, age, and diagnoses. Physical
      restraint was preferred more often with male, younger, and nonpsychotic patients.
      Pharmacological restraint was preferred more often with female patients and older
      patients with a nonorganic psychotic disorder. Seclusion was preferred more often
      with older male patients with an organic psychotic disorder.

PMID- 12191042
TI  - 'It is a different war to fight here in Sweden'--the impact of involuntary
      migration on the health of refugee families in transition.
AB  - Involuntary migration and adaptation to a new cultural environment is known to be
      a stress factor. The aim of the study was to explore the impact of involuntary
      migration on the family health in order to identify specific health care issues
      related to refugee families in transition living in Sweden. Data was collected
      through interviews with 16 members of 10 different refugee families from Balkan
      countries, Kurdistan and Africa for which permission was obtained from the
      chairman of the local ethnic organizations in a municipality in the southern part
      of Sweden. In interpreting the material, analysis was made using a contextual
      approach with reference to phenomenography. The analysis resulted in four
      qualitatively different descriptive categories characterizing the health of the
      families: a distressed family living under prolonged tension; a contented family
      who leads a satisfactory life; a frustrated family who cannot lead a fully
      satisfactory life and a dejected family who feels deserted. Stressors seeking
      asylum, facing unemployment and changed roles, interacted negatively within the
      family. A friendly and understanding attitude from the host country was the main
      factor in promoting the health of the refugee families. Nursing interventions
      should therefore assist the families accordingly in order to promote the
      stability of the family system.

PMID- 12191043
TI  - Disability after a stroke and the influence of long-term pain on everyday life.
AB  - Pain after a stroke is a symptom often forgotten, unnoticed although it is
      reported to be a great problem in care. The aim of this study was to describe
      disability after a stroke and how long-term pain influences everyday life
      according to the Multidimensional Pain Inventory - Swedish language version (MPI
      S) and to test the reliability of this instrument. Forty-three persons were
      investigated 2 years after the stroke incident: 15 with central post-stroke pain
      (CPSP), 18 with nociceptive pain mainly in the shoulder and 10 with tension-type
      headache. Data collection was performed through the MPI-S and a questionnaire
      regarding assistive devices, also structured interviews based on the Activities
      of Daily Living (ADL) staircase and the Self-report impairment questionnaire. The
      results show that the persons suffered moderate to severe pain. Almost half were
      dependent in ADL. The most often reported impairments and use of assistive
      devices concerned mobility and/or motion. This was most frequent in persons with
      nociceptive pain. There were significant differences in persons with central pain
      and nociceptive pain compared with tension-type headache with regard to mobility-
      and/or motion-related activities. No statistical differences emerged between age,
      gender, different types of pain and the MPI-S scales, nor any significant
      differences in degree of pain as between different types of pain according to the
      Self-report impairment questionnaire. The reliability analysis of the MPI-S shows
      good homogeneity in all scales except Interference, Life Control and Affective
      Distress. This is the first study with MPI-S on mainly older persons and on
      stroke patients, thus further research is needed on this instrument as well as on
      which specific activities evoke the pain. This is in order to offer adequate
      treatment, care and support to persons with pain after a stroke.

PMID- 12191044
TI  - Oral health and nutritional status in a group of geriatric rehabilitation
      patients.
AB  - The aims of this study were to evaluate the oral health status and nutritional
      status in a group of geriatric rehabilitation patients, and to analyse the
      relationship between these two parameters. Nurses at the ward performed
      structured assessments of oral and nutritional status using the Revised Oral
      Assessment Guide and the Subjective Global Assessment form in 223 newly admitted
      patients. Most oral health problems were found among patients who stayed longer
      at the hospital and were more dependent on help as compared with the healthier
      patients. Thirty-four per cent of the patients were either severely
      undernourished, at risk or suspected to be undernourished (UN). Oral health
      problems were more common among UN patients (p < 0.0005) compared with well
      nourished patients. The most frequent oral health problem was found on teeth or
      dentures (48%). Problems related to the tongue and lips were also common among UN
      patients (56 and 44%, respectively). Oral health status was correlated (r = 0.32)
      to nutritional status. Problems with swallowing had the strongest association to
      the nutritional status (OR 6.05; 95% CI 2.41-15.18). This study demonstrated that
      poor oral health status was related to undernourishment.

PMID- 12191045
TI  - Managing pain in older persons who receive home-help for their daily living.
      Perceptions by older persons and care providers.
AB  - Pain is a common problem for older persons who need professional help for their
      daily living. In this study 94 older persons (75+) in persistent pain were
      compared with 52 care providers concerning the pain management methods they had
      used/administered during the previous week and how helpful they perceived these
      methods to be. Interviews were based on 16 items from the original version of the
      pain management inventory (PMI). Both groups perceived prescribed medication,
      rest and distraction as the most frequently utilized methods. Specific methods
      such as transcutaneous electrical nerve stimulation (TENS) or bracing/splinting
      or bandaging the affected body part were seldom employed, although most users
      perceived these methods as helpful. Care providers perceived most methods for
      managing pain as more effective than older persons did. The results imply that
      care providers need skills in a variety of pharmacological and nonpharmacological
      methods to manage pain and a need to evaluate effectiveness of the methods in a
      systematic way.

PMID- 12191046
TI  - Measuring the experiences of health care for patients with musculoskeletal
      disorders (MSD): development of the Picker MSD questionnaire.
AB  - Analysis of data from a survey of patients with musculoskeletal problems (mainly
      back and neck pain) to develop a core measure of patients' experiences of health
      care. A secondary purpose was to determine whether a single summary index figure
      could be generated from the instrument. The data reported here comes from a
      postal survey of patients attending a spine clinic in Stockholm, Sweden. After
      attending the clinic patients were mailed a questionnaire. Up to two reminders
      were sent to nonresponders. Questionnaires were sent to 342 patients. Totally 173
      (51%) questionnaires were returned, of which 38.1% respondents were male and
      61.2% female. The mean age of patients was 54 years (SD 13.84), ranging from 16
      to 88. Sixteen items on the questionnaire were found to constitute a reliable
      index of patient experience and which seem to be tapping the most important
      aspects of patient experience. The index score was found to have high construct
      validity. The instrument provides a core set of issues that should be covered
      when assessing the quality of care patients attending clinics for musculoskeletal
      disorders.

PMID- 12191048
TI  - Improving student learning.

PMID- 12191049
TI  - Bottom drawer papers: another waste of clinicians' time.

PMID- 12191050
TI  - Can clinical reasoning be taught or can it only be learned?

PMID- 12191051
TI  - Teaching of occupational medicine to undergraduates in UK schools of medicine.
AB  - OBJECTIVES: To assess any recent change in the commitment to teaching of
      occupational medicine in UK undergraduate medical curricula. DESIGN: A
      questionnaire survey of the teaching of occupational medicine to undergraduates
      in all medical schools listed in the UK Universities and Colleges Admissions
      Service prospectus for 1999-2000 (n = 24). RESULTS: Nineteen UK medical schools
      returned a completed questionnaire, giving a response rate of 79%. A comparison
      of results from this survey with previous surveys of teaching of occupational
      medicine to undergraduates in the UK shows that fewer schools now provide
      lectures, project work or ward-based tuition in the subject. Workplace visits
      were not undertaken by any institution. Only two of the schools setting an
      examination question also had a syllabus. CONCLUSION: Despite the prominence
      given to issues related to occupational health in recent UK government policy,
      this study suggests a declining commitment to occupational medicine on the part
      of UK medical schools. Urgent action needs to be taken to address the lack of
      training in occupational medicine in UK medical schools.

PMID- 12191052
TI  - Anatomy 1999-2000: the curriculum, who teaches it and how?
AB  - AIM: To review the impact of Tomorrow's Doctors on anatomical teaching in the UK
      and Ireland. To establish in particular whether a consensus has emerged on: (a)
      the duration and format of teaching, and (b) the impact on staffing and on the
      four main anatomical disciplines of gross anatomy, histology, embryology and
      neuroanatomy. METHOD AND RESULTS: A postal survey of 28 anatomy departments was
      carried out. This yielded a response rate of 75%. Twelve departments used systems
      based curricula, five used problem-based curricula, and four used a traditional
      regional format. There were variable levels of integration between the anatomical
      disciplines and subjects outside anatomy. Dissection taught over the first 2
      years was retained in 76% of the courses, frequently supplemented with
      demonstrations, with an average of 2 hours of practical work for every hour of
      lecture. Staff/student ratios varied with the type of curriculum: dissection room
      teaching and problem-based curricula were associated with higher numbers of
      either full or part-time clinically qualified teachers. Teaching was supported by
      a high proportion of part-time clinically qualified staff, giving an overall
      average staff/student ratio of 19.8 in a dissection class. CONCLUSIONS: There is
      considerable variation in duration and staffing of anatomy teaching, according to
      the type of curriculum. This suggests there may well be substantial variation in
      the level, content and depth of anatomical curricula across the country, and that
      this should be quantified.

PMID- 12191053
TI  - Growth of medical knowledge.
AB  - BACKGROUND: Knowledge is an essential component of medical competence and a major
      objective of medical education. Thus, the degree of acquisition of knowledge by
      students is one of the measures of the effectiveness of a medical curriculum. We
      studied the growth in student knowledge over the course of Maastricht Medical
      School's 6-year problem-based curriculum. METHODS: We analysed 60 491 progress
      test (PT) scores of 3226 undergraduate students at Maastricht Medical School.
      During the 6-year curriculum a student sits 24 PTs (i.e. four PTs in each year),
      intended to assess knowledge at graduation level. On each test occasion all
      students are given the same PT, which means that in year 1 a student is expected
      to score considerably lower than in year 6. The PT is therefore a longitudinal,
      objective assessment instrument. Mean scores for overall knowledge and for
      clinical, basic, and behavioural/social sciences knowledge were calculated and
      used to estimate growth curves. FINDINGS: Overall medical knowledge and clinical
      sciences knowledge demonstrated a steady upward growth curve. However, the curves
      for behavioural/social sciences and basic sciences started to level off in years
      4 and 5, respectively. The increase in knowledge was greatest for clinical
      sciences (43%), whereas it was 32% and 25% for basic and behavioural/social
      sciences, respectively. INTERPRETATION: Maastricht Medical School claims to offer
      a problem-based, student-centred, horizontally and vertically integrated
      curriculum in the first 4 years, followed by clerkships in years 5 and 6.
      Students learn by analysing patient problems and exploring pathophysiological
      explanations. Originally, it was intended that students' knowledge of
      behavioural/social sciences would continue to increase during their clerkships.
      However, the results for years 5 and 6 show diminishing growth in basic and
      behavioural/social sciences knowledge compared to overall and clinical sciences
      knowledge, which appears to suggest there are discrepancies between the actual
      and the planned curricula. Further research is needed to explain this.

PMID- 12191054
TI  - Building confidence for work as house officers: student experience in the final
      year of a new problem-based curriculum.
AB  - INTRODUCTION: Newly qualified doctors require an appropriate level of confidence
      for their new roles. Development of this confidence was a key objective in the
      final year of a new integrated course with an emphasis on student self-direction.
      CONTEXT: There are 5 placements in the final year course. Students use a Learning
      Planner to help them choose suitable placements and objectives to serve their
      learning needs. Educational supervision focuses on helping students determine
      their objectives and assessing them against these. METHODS: Course evaluation was
      by means of a questionnaire during final assessments. Cohorts of 310 and 316
      students in successive years completed the evaluation. The interrelationship
      between variables was explored using logistic regression. RESULTS: 220/310
      students in the 2000 cohort and 214/316 in the 2001 cohort agreed they felt
      confident with their prospective role as a pre-registration house officer (PRHO).
      Confidence was significantly associated with confidence in their clinical skills,
      belief in their ability to cope with uncertainty and feeling able to work as a
      team member. The experience of the 2 hospital placements and (in 2000 only) the
      elective was associated with increased confidence. In all placements helpful
      educational supervision and the achievement of the self-directed learning plan
      was associated with increased confidence as a potential doctor. CONCLUSION:
      Students perceive a relationship between learning experiences in the final year
      of a self-directed course and development of confidence for their future role.
      Whilst further elucidation of the nature of this relationship is required, this
      provides encouragement to curriculum planners to promote self-direction.

PMID- 12191055
TI  - Forming professional identities on the health care team: discursive constructions
      of the 'other' in the operating room.
AB  - BACKGROUND: Inter-professional health care teams represent the nucleus of both
      patient care and the clinical education of novices. Both activities depend upon
      the'talk' that team members use to interact with one another. This study explored
      team members' interpretations of tense team communications in the operating room
      (OR). METHODS: The study was conducted using 52 team members divided into 14
      focus groups. Team members comprised 13 surgeons, 19 nurses, nine anaesthetists
      and 11 trainees. Both uni-disciplinary (n = 11) and multi-disciplinary (n = 3)
      formats were employed. All groups discussed three communication scenarios,
      derived from prior ethnographic research. Discussions were audio-recorded and
      transcribed. Using a grounded theory approach, three researchers individually
      analysed sample transcripts, after which group discussions were held to resolve
      discrepancies and confirm a coding structure. Using the confirmed code, the
      complete data set was coded using the 'NVivo' qualitative data analysis software
      program. RESULTS: There were substantial differences in surgeons', nurses',
      anaesthetists', and trainees' interpretations of the communication scenarios.
      Interpretations were accompanied by subjects' depictions of disciplinary roles on
      the team. Subjects' constructions of other professions' roles, values and
      motivations were often dissonant with those professions' constructions of
      themselves. CONCLUSIONS: Team members, particularly novices, tend to simplify and
      distort others' roles and motivations as they interpret tense communication. We
      suggest that such simplifications may be rhetorical, reflecting professional
      rivalries on the OR team. In addition, we theorise that novices' echoing of role
      simplification has implications for their professional identity formation.

PMID- 12191056
TI  - Students' perceptions of relationships between some educational variables in the
      out-patient setting.
AB  - BACKGROUND: Medical education uses the cognitive apprenticeship model of student
      learning extensively. Students rotate among different hospitals and out- patient
      clinics where they are exposed to a range of professionally relevant contexts.
      Here they learn to think and act in different domains under the supervision of
      experts. Previous research has shown that these learning situations involve
      little teaching. Students see a narrow range of patient problems and feedback is
      limited. The aim of this study is to investigate relationships among some
      educational variables in the out-patient clinic. METHOD: This paper provides a
      theoretical model that specifies the factors influencing the effectiveness of
      student rotations at out-patient clinics. The model makes distinctions between
      input variables, such as organizational quality, number of students
      contemporaneously involved and available space, and process variables, such as
      patient mix and supervision, and the output variable of the effectiveness of
      rotations in out-patient clinics. RESULTS: The model was tested against empirical
      data from evaluative surveys and showed a reasonable fit. The model offers
      suggestions for improving the learning environment of clinical rotations.
      DISCUSSION: The strength of this study lies in its process evaluation perspective
      which investigates interactions between intervening variables rather than the
      influence of particular variables in isolation from other variables.

PMID- 12191057
TI  - The challenge of creating new OSCE measures to capture the characteristics of
      expertise.
AB  - PURPOSE: Although expert clinicians approach interviewing in a different manner
      than novices, OSCE measures have not traditionally been designed to take into
      account levels of expertise. Creating better OSCE measures requires an
      understanding of how the interviewing style of experts differs objectively from
      novices. METHODS: Fourteen clinical clerks, 14 family practice residents and 14
      family physicians were videotaped during 2 15-minute standardized patient
      interviews. Videotapes were reviewed and every utterance coded by type including
      questions, empathic comments, giving information, summary statements and
      articulated transitions. Utterances were plotted over time and examined for
      characteristic patterns related to level of expertise. RESULTS: The mean number
      of utterances exceeded one every 10 s for all groups. The largest proportion was
      questions, ranging from 76% of utterances for clerks to 67% for experts. One
      third of total utterances consisted of a group of 'low frequency' types,
      including empathic comments, information giving and summary statements. The topic
      was changed often by all groups. While utterance type over time appeared to show
      characteristic patterns reflective of expertise, the differences were not robust.
      Only the pattern of use of summary statements was statistically different between
      groups (P < 0.05). CONCLUSIONS: Measures that are sensitive to the nature of
      expertise, including the sequence and organisation of questions, should be used
      to supplement OSCE checklists that simply count questions. Specifically,
      information giving, empathic comments and summary statements that occupy a third
      of expert interviews should be credited. However, while there appear to be
      patterns of utterances that characterise levels of expertise, in this study these
      patterns were subtle and not amenable to counting and classification.

PMID- 12191058
TI  - Primary care resident, faculty, and patient views of barriers to cultural
      competence, and the skills needed to overcome them.
AB  - INTRODUCTION: Primary care residencies are expected to provide training in
      cultural competence. However, we have insufficient information about the
      perceptions of stakeholders actually involved in healthcare (i.e. residents,
      faculty and patients) regarding commonly encountered cross-cultural barriers and
      the skills required to overcome them. METHOD: This study used a total of 10 focus
      groups to explore resident, faculty and patient attitudes and beliefs about what
      culturally competent doctor-patient communication means, what obstacles impede or
      prevent culturally competent communication, and what kinds of skills are helpful
      in achieving cultural competence. A content analysis was performed to identify
      major themes. RESULTS: Residents and faculty defined culturally competent
      communication in terms of both generic and culture-specific elements, however,
      patients tended to emphasize only generic attitudes and skills. Residents and
      patients were liable to blame each other in explaining barriers; faculty were
      more likely to consider systemic influences contributing to resident-patient
      difficulties. All groups emphasized appropriate skill and attitude development in
      learners as the key to successful communication. However, residents were
      sceptical of sensitivity and communication skills training, and worried that
      didactic presentations would result in cultural stereotyping. DISCUSSION: All
      stakeholders recognized the importance of effective doctor-patient communication.
      Of concern was the tendency of various stakeholders to engage in person-blame
      models.

PMID- 12191059
TI  - Promoting diagnostic problem representation.
AB  - PURPOSE: Problem representation, as mediated by semantic qualifiers (SQs), has
      been associated with better diagnostic outcomes. The purpose of this study was to
      assess the effect of training medical students to use semantic abstractions as a
      means of building problem representations. METHODS: Sixty second-year medical
      students were assigned to either an intervention group (n = 20) or a control
      group (n = 40) during 8 months of an Essentials in Clinical Medicine course which
      used standardized patient-based workshops. Students were trained to transform
      findings into SQs and to use abstractions to compare and contrast diagnostic
      hypotheses. Students were assessed using a standardized patient data collection
      checklist, a post-encounter patient finding questionnaire (PFQ), and case
      summaries and write-ups. RESULTS: Experimental subjects used over twice as many
      SQs in their summaries as control group members (1.40 versus 0.63, P = 0.006).
      The correlation between checklist and PFQ scores was higher for the experimental
      group than for the control group (r = 0.70 versus r = 0.58, P </= 0.001). There
      was no difference between groups in either the number of SQs used in write-ups
      nor in diagnostic accuracy (P > 0.56). CONCLUSION: A short instructional
      intervention was successful in promoting the use of SQs and enabled students to
      recall elicited findings better. This intervention did not enhance data
      interpretation and diagnostic accuracy. Use of SQs may therefore be a necessary
      tool for efficient problem representation but one that is insufficient when used
      in isolation. The naturalistic setting used in this study imposed a number of
      limitations, implying that further research should test whether instructional
      efforts should also emphasize recognition of key patient findings and knowledge
      representation.

PMID- 12191060
TI  - An electronic learning portfolio for reflective continuing professional
      development.
AB  - OBJECTIVES: These were to measure the uptake and use of an electronic learning
      portfolio to support reflective continuing professional development, and to
      characterize attitudes towards its use and obstacles to its adoption. DESIGN:
      Uncontrolled, longitudinal intervention study with quantitative and qualitative
      evaluation. PARTICIPANTS: Physicians with a specialty interest in endocrinology
      and diabetes mellitus, registered for continuing professional development with
      the Royal College of Physicians, London. INTERVENTION: All registered consultants
      were offered a 1-year free trial of PC Diary. Those who accepted were offered a
      training workshop. MAIN OUTCOME MEASURES: Quantitative and qualitative responses
      to a simple questionnaire. Two researchers independently used a template approach
      to analyse free-text responses and jointly agreed a final system of coding.
      RESULTS: 22% of registered consultants applied to participate; 14% attended
      training workshops. Of registered participants, 94% returned the questionnaire.
      PC Diary was used by 34%, but only 10% used it regularly. Among the registrants,
      54% asked to continue their subscription for a second year, and 40% asked for
      further training. There were emotive expressions of both like and dislike, often
      coupled with statements about the individual's learning style. Time pressures and
      lack of computer access, literacy and support were dominant obstacles to
      adoption. CONCLUSIONS: There was considerable support for reflective learning
      using an electronic portfolio. Acceptability and use were influenced by
      individual learning style, resources, training and technical support, and these
      were often inadequate. The balance for consultants between workload demands and
      support provided did not favour a reflective type of learning.

PMID- 12191061
TI  - The value of clinical judgement analysis for improving the quality of doctors'
      prescribing decisions.
AB  - BACKGROUND: Many initiatives are taken to improve prescribing decisions.
      Educational strategies for doctors have been effective in at least 50% of cases.
      Some reflection on one's own performance seems to be a common feature of the most
      effective strategies. So far, such reflections have mainly focused on the
      observed outcomes of the doctors' decisions, i.e. on what doctors do in practice.
      Studies in other fields have shown that another form of feedback based on the
      analysis of judgements may be useful as well. OBJECTIVES: The objectives of the
      study were to discuss the principles underlying clinical judgement analysis, give
      examples of its use in the medical context, and discuss its potential for
      improving prescribing decisions. RESULTS: Clinical judgement analysis can look
      behind the outcome of a decision to the underlying decision process. Carefully
      constructed or selected case material is required for this analysis. Combining
      feedback on outcomes with feedback based on clinical judgement analysis offers
      doctors insight both in what they do, and why or when they do it. It may reveal
      determinants of decision making which are not available through unaided
      introspection. Interventions using this combination of feedback for improving
      doctors' prescribing behaviour have been (partly) successful in 4 cases and
      unsuccessful in one case. CONCLUSIONS: Clinical judgement analysis gives doctors
      a structured reflection on the decision-making policy, and can help them to
      improve their future decisions. It may be especially useful for groups of doctors
      who try to work towards a consensus policy. The approach is not very helpful when
      simple decision rules are appropriate.

PMID- 12191062
TI  - Factors influencing prescribing: an intern's perspective.
AB  - OBJECTIVES: To examine the self-reported influences on intern prescribing
      practice. DESIGN: Qualitative interviews with a cross-sectional cohort.
      PARTICIPANTS AND SETTING: Ten interns practising in two urban teaching hospitals
      in New South Wales, Australia. RESULTS: The interns identified a number of
      factors that improve their confidence and perceived competence and allow them to
      extend their existing skills. These were approachable, available and up-to-date
      teachers (most often registrars and subspecialty nurses and pharmacists); timely,
      relevant and practical teaching (such as interactive bedside teaching); concise
      and widely accepted resources (such as prescribing pocket guides); and a
      constructive manner on the part of senior staff for dealing with prescribing
      errors. Interns also identified influences that are detrimental to confidence,
      conflict with their perceptions of appropriate prescribing and inhibit learning
      and skills acquisition. These were unapproachable, physically and mentally remote
      teachers (most often consultants); theoretical, inconsistent and irrelevant
      teaching (such as grand rounds or didactic education sessions); inconsistent and
      inaccessible resources; and a confrontational and accusatory way of dealing with
      prescribing errors. The added pressures of time, hospital hierarchies and the
      indirect influence of drug company promotion also impeded acquisition of good
      prescribing habits. CONCLUSIONS: At a critical time in skills development,
      interns encounter many forces that can potentially impact on prescribing
      practices in both positive and negative ways. Our data contribute to the
      understanding of the multifaceted learning environment of interns and may be
      useful in providing a foundation for prescriber education programmes tailored to
      the specific needs of junior doctors.

PMID- 12191063
TI  - Disability teaching for medical students: disabled people contribute to
      curriculum development.

PMID- 12191064
TI  - Problems with problems in problem-based curricula.

PMID- 12191065
TI  - Consequences of tomorrow's doctors.

PMID- 12191066
TI  - Can students in a modified PBL curriculum exceed the national mean on USMLE Part
      1?

PMID- 12191067
TI  - Effect of an early rural placement on internship choices of medical students.

PMID- 12191071
TI  - Absenteeism among nursing students - fact or fiction?
AB  - This study explores absenteeism patterns and trends among a group of third-year
      student nurses. A questionnaire was used to elicit information about absence
      behaviour from 110 students at two hospital sites. Retrospective analysis of
      attendance records of 70 of these students, covering a period of 123 weeks, was
      also performed to determine absenteeism trends. The findings of the study reveal
      that 1567 days were lost because of absenteeism during this period on 1027
      episodes. This represents a time lost index, which is the amount of days lost
      expressed as a percentage of total days available, of 4% among the group. Most
      absenteeism episodes lasted 3 days or less, with 73% of episodes lasting only 1
      day. Absenteeism commencing either on Mondays or Fridays accounted for more than
      half of the absenteeism episodes in the group. Voluntary absence was a reported
      feature of this group, which occurred more frequently from lectures than wards.
      The main reasons cited for absence from both lectures and ward duties were
      personal and social commitments and stress. Students' views on nursing as a
      career and responses to factors that may cause stress were examined and revealed
      an association with reported absence behaviour.

PMID- 12191072
TI  - A Delphi survey of evidence-based nursing priorities in Hong Kong.
AB  - The purpose of this study was to inform an evidence-based nursing development
      project within the Hospital Authority, Hong Kong. It considered the specific
      question of: what are the nursing practice issues which need to be addressed as a
      matter of priority in order to improve nursing practice, the quality of care or
      develop some aspect of nursing practice. A three round Delphi survey was adopted.
      The methodological problems associated with the use of the Delphi method are
      addressed. An expert panel consisting of 190 Department Operations Managers
      (nurses) was identified. The data collection focused on issues related to nursing
      skills and client care and excluded management or educational issues. Agreed
      categories were prioritized in the final round by utilizing a 11-point rating
      scale. The group mean score for each category was calculated and rank ordered.
      The results provided 45 categories that reflected the nursing practice priorities
      that required more research evidence to guide practice. The top five ranked items
      were: nurse patient communication, resuscitation, administration of medicines,
      counselling and nursing documentation. The top 10 items were used to inform the
      advisory and selection processes for the evidence-based practice development
      project.

PMID- 12191073
TI  - Clinical supervision using video-conferencing technology: a reflective account.
AB  - This paper discusses three nursing practitioners' experiences of clinical
      supervision using video-conferencing (VC) technology. The study, based on
      supportive action research, involved 40 practising community and hospital nurses
      from a variety of specialties and took place over an 18-month period. The
      research was collaborative, educational and applied and focused on the effects of
      remote clinical supervision on the development of professional practice. Data
      were obtained through pre- and post-study questionnaires, repertory grids, focus
      group interviews and written narratives. The three research participants found
      that clinical supervision, as a mediator of learning, was vital in enabling them
      to develop their reflective and problem-solving skills. Through critical
      conversations with either a supervisor or within peer group supervision, the
      participants increased both their confidence and self-awareness and gained more
      insight into the practices and needs of other practitioners. They also examined
      critically patient care issues resulting in attention to existing or the
      development of new care protocols. They did, however, experience some impediments
      to the process of clinical supervision, mainly lack of peer and management
      support and ongoing education. The participants had mixed perceptions with
      regards to using VC technology for clinical supervision. They experienced
      technical and accessibility problems and communication problems, suggesting the
      need for clear protocols for both technical support and applied training.

PMID- 12191074
TI  - Primary care groups and trusts: a threat or an opportunity for the development of
      community-based nursing in England.
AB  - AIMS OF THE STUDY: To examine the role of Primary Care Groups and Trusts (PCG/T)
      in relation to nurses working in general practice and community health services.
      BACKGROUND: Over the past two decades there have been rapid changes in the
      numbers and roles of nurses working in primary care and community based settings.
      The establishment of Primary Care Groups offers health care professionals,
      including nurses, the chance to develop local primary care services and to
      integrate community and primary care nursing. These developments may offer
      opportunities or pose threats to nursing staff. RESEARCH METHODS: Data are drawn
      from a longitudinal study of a randomly selected sample of Primary Care Groups in
      England (n = 72). In a second survey of Groups carried out in autumn/winter 2000,
      Primary Care Group chairs and chief officers were interviewed by telephone.
      RESULTS: Response rates were 97% for both chairs and chief officers (69 of each).
      Chairs indicated that in most areas Primary Care Groups were consulting with
      local nurses to develop policy. Fifty-seven (85%) reported that investment in
      nursing staff and nursing services was a high priority in their area. Twenty
      eight (41%) indicated that nurse-led services designed to increase patient access
      had already been established in their area, and 20 (29%) were planning new nurse
      led services. Many developments had been initiated by Primary Care Groups.
      Initiatives to integrate community and general practice based staff were underway
      in most areas. CONCLUSIONS: Primary Care Groups and Trusts are initiating changes
      in general practice and community based services which are likely to have long
      term and important implications for nurses in terms of their roles, conditions of
      work and future careers. It is important that nurses are consulted and are
      involved in developing and implementing policy change.

PMID- 12191075
TI  - Shared governance in the community.
AB  - This paper summarizes the findings from an evaluation of the Locality
      Partnerships project. This project represented an attempt to introduce the
      principles of shared governance into a community health setting. Particular
      emphasis is given to the findings related to the involvement of staff in decision
      making, communication and information flow, and the job satisfaction of staff.
      The paper finds that staff who had been most involved in the project reported
      improvements in all of these areas; however, there were no comparable gains for
      those staff who were less directly involved. In conclusion, it is suggested that
      although the principles of shared governance are in accordance with government
      policy this project saw their incomplete assimilation into the community health
      setting.

PMID- 12191076
TI  - Side rails as physical restraints in the care of older people: a management
      issue.
AB  - This article explores the use of side rails within the context of physical
      restraint in gerontological practice. It is debated that side rails can be
      considered as a form of physical restraint if the individual cannot voluntarily
      remove/lower the device if he/she wishes to do so. The value of side rails as a
      protective medium is debated with regard to their association with injuries
      sustained as a result. Side rails should be used with caution and within a risk
      management context. Frailty should not be an indicator for the use of side rails,
      an individualized approach to determine patient's suitability to side rails is
      advocated.

PMID- 12191432
TI  - Comparison of deferral rates using a computerized versus written blood donor
      questionnaire: a randomized, cross-over study [ISRCTN84429599].
AB  - BACKGROUND: Self-administered computer-assisted blood donor screening strategies
      may elicit more accurate responses and improve the screening process. METHODS:
      Randomized crossover trial comparing responses to questions on a computerized
      hand-held tool (HealthQuiz, or HQ), to responses on the standard written
      instrument (Donor Health Assessment Questionnaire, or DHAQ). Randomly selected
      donors at 133 blood donation clinics in the area of Hamilton, Canada participated
      from 1995 to 1996. Donors were randomized to complete either the HQ or the DHAQ
      first, followed by the other instrument. In addition to responses of 'yes' and
      'no' on both questionnaires, the HQ provided a response option of 'not sure'. The
      primary outcome was the number of additional donors deferred by the HQ. RESULTS:
      A total of 1239 donors participated. Seventy-one potential donors were deferred
      as a result of responses to the questionnaires; 56.3% (40/71) were deferred by
      the DHAQ, and an additional 43.7% (31/71) were deferred due to risks identified
      by the HQ but not by the DHAQ. Fourteen donors self-deferred; 11 indicated on the
      HQ that they should not donate blood on that day but did not use the confidential
      self-exclusion option on the DHAQ, and three used the self-exclusion option on
      the DHAQ but did not indicate that they should not donate blood on the HQ. The HQ
      identified a blood contact or risk factor for HIV/AIDS or sexually transmitted
      infection that was not identified by the DHAQ in 0.1% to 2.7% of donors.
      CONCLUSION: A self-administered computerized questionnaire may increase risk
      reporting by blood donors.

PMID- 12191435
TI  - Developmental and reproductive biology of Scirtothrips perseae (Thysanoptera:
      Thripidae): a new avocado pest in California.
AB  - The developmental and reproductive biology of a new avocado pest, Scirtothrips
      perseae Nakahara, was determined in the laboratory at five constant temperatures,
      15, 20, 25, 27.5 and 30 degrees C. At 20 degrees C, S. perseae exhibited greatest
      larval to adult survivorship (41%), and mated females produced a greater
      proportion of female offspring at this temperature when compared to 15, 25, 27.5
      and 30 degrees C. Average lifetime fecundity and preoviposition period was
      greatest at 15 degrees C at 39.6 eggs per female and 17.6 days, respectively.
      Jackknifed estimates of net reproduction (Ro), capacity for increase (rc),
      intrinsic rate of increase (rm), and finite rate of increase (lambda) were all
      significantly greater at 20 degrees C than corresponding values at 15, 25 and
      27.5 degrees C. Population doubling time (Td) was significantly lower at 20
      degrees C, indicating S. perseae populations can double 33-71% faster at this
      temperature in comparison to 15, 25 and 27.5 degrees C. Mean adult longevity
      decreased with increasing temperature, from a maximum of 52.4 days at 15 degrees
      C to a minimum of 2.4 days at 30 degrees C. Developmental rates increased
      linearly with increasing temperatures for eggs and rates were non-linear for
      development of first and second instar larvae, propupae, pupae, and for egg to
      adult development. Linear regression and fitting of the modified Logan model to
      developmental rate data for egg to adult development estimated that 344.8 day
      degrees were required above a minimum threshold of 6.9 degrees C to complete
      development. An upper developmental threshold was estimated at 37.6 degrees C
      with an optimal temperature of 30.5 degrees C for egg to adult development.
      Unmated females produced only male offspring confirming arrhenotoky in S.
      perseae.

PMID- 12191433
TI  - Mouse ribonuclease III. cDNA structure, expression analysis, and chromosomal
      location.
AB  - BACKGROUND: Members of the ribonuclease III superfamily of double-stranded(ds)
      RNA-specific endoribonucleases participate in diverse RNA maturation and decay
      pathways in eukaryotic and prokaryotic cells. A human RNase III orthologue has
      been implicated in ribosomal RNA maturation. To better understand the structure
      and mechanism of mammalian RNase III and its involvement in RNA metabolism we
      determined the cDNA structure, chromosomal location, and expression patterns of
      mouse RNase III. RESULTS: The predicted mouse RNase III polypeptide contains 1373
      amino acids (approximately 160 kDa). The polypeptide exhibits a single C-terminal
      dsRNA-binding motif (dsRBM), tandem catalytic domains, a proline-rich region
      (PRR) and an RS domain. Northern analysis and RT-PCR reveal that the transcript
      (4487 nt) is expressed in all tissues examined, including extraembryonic tissues
      and the midgestation embryo. Northern analysis indicates the presence of an
      additional, shorter form of the transcript in testicular tissue. Fluorescent in
      situ hybridization demonstrates that the mouse RNase III gene maps to chromosome
      15, region B, and that the human RNase III gene maps to a syntenic location on
      chromosome 5p13-p14. CONCLUSIONS: The broad transcript expression pattern
      indicates a conserved cellular role(s) for mouse RNase III. The putative
      polypeptide is highly similar to human RNase III (99% amino acid sequence
      identity for the two catalytic domains and dsRBM), but is distinct from other
      eukaryotic orthologues, including Dicer, which is involved in RNA interference.
      The mouse RNase III gene has a chromosomal location distinct from the Dicer gene.

PMID- 12191434
TI  - Key-factor analysis of immature stages of Aedes scapularis (Diptera: Culicidae)
      populations in southeastern Brazil.
AB  - Development times and mortality factors were investigated for populations of
      Aedes scapularis (Rondani) occurring in natural temporary ground pools in
      southeastern Brazil. Analysis of life tables by the key-factor method showed that
      mortality caused by desiccation of breeding sites was the principal factor
      accounting for fluctuations in population sizes throughout the study period. For
      cohorts that completed development, mortality attributed to predation by aquatic
      insects ranged from 68 to 96% and was the most important cause of death. In these
      cohorts, final population size was determined by the high mortality rates that
      occurred during the fourth larval instar and pupal stages; however, the key
      factor best accounting for the population fluctuations was predation of fourth
      instar larvae. The short mean time of 7.1 days for synchronous development of the
      larvae and the lack of evidence of density-dependent mortality suggested that the
      A. scapularis populations were not strongly regulated and can attain relatively
      high densities.

PMID- 12191436
TI  - The chemical characterization of the epicuticular hydrocarbons of Aedes aegypti
      (Diptera: Culicidae).
AB  - The chemical characterization of the hydrocarbon fraction of the epicuticular
      lipids of the vector mosquito Aedes aegypti (Linnaeus) was performed using gas
      chromatography (GC) and gas chromatography-electron impact mass spectrometry (GC
      MS). Seventy eight compounds were detected in purified hexane extracts and of
      these, 42 hydrocarbons were identified and several of the remaining compounds
      were partially characterized. The hydrocarbon classes present were n-alkanes,
      monomethylalkanes, dimethylalkanes and alkenes and the results were similar to
      those published for other Aedes species. Quantitative comparisons of cuticular
      hydrocarbon profiles were made between males and females, different age groups
      and between a standard laboratory strain and a recently colonized strain of A.
      aegypti. These results provide baseline data for further studies on the possible
      role of mosquito cuticular hydrocarbons in the modification of mating behaviour.

PMID- 12191438
TI  - Variation in the life cycle and morphology of the tobacco host-race of Myzus
      persicae (Hemiptera: Aphididae) in relation to its geographical distribution.
AB  - Morphological variation and life cycle category were examined in 121 clones of
      Myzus persicae (Sulzer). The clones were collected from tobacco from three
      localities in Greece (Xanthi, Nea Efessos and Naphplion), one in Germany
      (Rheinstetten), one in France (Bergerac) and one in Spain (Madrid). Before
      morphometrics, all aphids were laboratory-reared on potato. The morphological
      variation was investigated using both canonical variates analysis and a novel non
      parametric classification tree method. The life cycle category was examined by
      rearing the clones for three generations under short day conditions. In Nea
      Efessos a relative high proportion of clones was found to overwinter as eggs on
      the primary host. In the other regions all collected clones were non-holocyclic.
      Intermediate genotypes were found in all regions at percentages ranging from 4.0
      to 24.0%. Androcyclic clones were found only in Xanthi, Greece (4.0%) and
      Rheinstetten, Germany (16.7%). The canonical variates analysis and the tree
      classification method revealed important intrapopulation polymorphisms in clones
      from Bergerac, Nea Efessos and Madrid. Both methods separated the populations
      originating from Greece from those collected elsewhere in western Europe. The
      observed morphological variation was probably due to genetic differences, since
      all clones were reared in a common environment. The results are discussed in
      relation to factors responsible for genetic divergence in M. persicae
      populations.

PMID- 12191437
TI  - Comparison of attractiveness in Japan and China of three synthetic pheromone
      blends based on geographic variations in the rice leaffolder, Cnaphalocrocis
      medinalis(Lepidoptera: Pyralidae).
AB  - Field bioassays using three different synthetic sex pheromone blends (Indian,
      Philippine and Japanese) based on geographic variations of Cnaphalocrocis
      medinalis Guenee were carried out at 11 sites in Japan and in Hangzhou, China. In
      all of the tests, only the Japanese pheromone blend attracted a significant
      number of male moths, while the Indian and Philippine pheromone blends showed no
      marked activity. The findings in Japan showed no evidence that moths of
      Philippine or Indian origin were able to migrate to Japan. The results from China
      also showed that most populations of C. medinalisin the Hangzhou region responded
      to the Japanese blend. This is consistent with the current hypothesis that most
      populations of C. medinalisin Japan are migrants from areas to the south of the
      Yangzhe Valley, including the region surrounding Hangzhou, China. Furthermore,
      populations in the Hangzhou region can not hibernate, but are considered migrants
      from the southernmost parts of China and southeast Asian countries such as
      Vietnam where they breed continuously. Consequently, at least some populations in
      these areas may respond to the Japanese pheromone blend.

PMID- 12191439
TI  - Life cycle variation of Myzus persicae (Hemiptera: Aphididae) in Greece.
AB  - During the years 1995-1999 the life cycle category of 2797 clones of Myzus
      persicae (Sulzer) was examined. The clones originated from primary and secondary
      hosts from different localities of North and Central Greece and the island of
      Crete in the south. Four different overwintering life cycle strategies were found
      that have also been described for M. persicae and other heteroecious species
      previously. A geographical variation was found in the proportion of holocyclic
      clones from tobacco and other secondary hosts associated with the abundance of
      the primary host in the sampling regions. In Central Macedonia, around the main
      peach-growing regions, the proportion of holocyclic clones was mostly above 50%
      and in some cases reached 100%. In localities of East Macedonia, holocyclic
      clones were also frequent. On the other hand, further south or in north-eastern
      Greece, where peach is not common, the proportion of holocyclic clones varied
      between 0 and 33%. Fifty seven percent of examined anholocyclic clones produced
      males under short day conditions, suggesting that androcyclic clones in Greece
      represent an important factor of genetic variability. Intermediate clones were
      sampled from all host-plants but at low frequencies (3.6% of total examined
      clones and 6.9% of non-holocyclic ones). Moreover, a regional variation was found
      in different colour forms feeding on tobacco plants. Red clones were predominant
      in regions where aphids overwinter parthenogenetically on weeds or winter crops.
      However, almost all clones from the primary host were green. The ecological
      aspects of life cycle variation are discussed.

PMID- 12191440
TI  - Production of sexual morphs by apterous virginoparae of Myzus persicae
      (Hemiptera: Aphididae) in relation to pre- and postnatal exposure to short day
      conditions.
AB  - The production of males and females by apterae of a holocyclic clone of Myzus
      persicae (Sulzer) was studied in the laboratory by transferring apterous
      virginoparae from long day to short day conditions at different stages of their
      pre- and post-natal development. Prenatal exposure was also examined in nine
      additional clones coming from different regions of Greece. By increasing the
      number of short day cycles at 17 degrees C, the aphids switched to male
      production earlier and produced more males. The highest mean number of male
      progeny was observed in apterae that were transferred to short day conditions 13
      14 days prenatally. Apterae that were transferred to short day conditions after
      the fourth nymphal instar produced only females. Apterous virginoparae were
      produced by aphids that were transferred to short day conditions 0-1 days
      prenatally or postnatally. Aphids, given short days prenatally or in the first
      instar, produced alate female progeny that were all gynoparae. The later the
      instar aphids were transferred to short day conditions the fewer the gynoparae
      produced among their female progeny. A reduction in the total number of progeny
      and embryos per ovariole was observed as aphids were transferred to short day
      conditions in earlier stages of their development. The increase in male
      production, which follows the increase in the duration of long night exposure,
      was also observed in the additional eight out of nine examined clones.

PMID- 12191441
TI  - Digestive proteinases in Lasioderma serricorne (Coleoptera: Anobiidae).
AB  - The cigarette beetle, Lasioderma serricorne (Fabricius), is a common pest of
      stored foods. A study of digestive proteinases in L. serricorne was performed to
      identify potential targets for proteinaceous biopesticides, such as proteinase
      inhibitors. Optimal casein hydrolysis by luminal proteinases of L. serricorne was
      in pH 8.5-9.0 buffers, although the pH of luminal contents was slightly acidic.
      Results from substrate and inhibitor analyses indicated that the primary
      digestive proteinases were serine proteinases. The most effective inhibitors of
      caseinolytic hydrolysis were from soybean (both Bowman Birk and Kunitz), with
      some inhibition by chymostatin, N-tosyl-L-phenylalanine chloromethyl ketone, and
      leupeptin. Casein zymogram analysis identified at least eight proteolytic
      activities. Activity blot analyses indicated one major proteinase activity that
      hydrolysed the trypsin substrate N-alpha-benzoyl-L-arginine rho-nitroanilide, and
      three major proteinase activities that hydrolysed the chymotrypsin substrate N
      succinyl ala-ala-pro-phe rho-nitroanilide. The absence of cysteine, aspartic, and
      metallo proteinases in L. serricorne digestion was evidenced by the lack of
      activation by thiol reagents, alkaline pH optima, and the results from class
      specific proteinase inhibitors. The data suggest that protein digestion in L.
      serricorne is primarily dependent on trypsin- and chymotrypsin-like proteinases.

PMID- 12191442
TI  - PCR-RFLP identification of endemic Chilean species of Rhagoletis (Diptera:
      Tephritidae) attacking Solanaceae.
AB  - Four species of the genus Rhagoletis are native to Chile: R. nova (Schiner), R.
      conversa, (Brethes), R. penela Foote and R. tomatis Foote. Currently,
      identification of these species is based on morphological criteria, but their
      strong similarity makes precise recognition difficult. To clarify species
      separation for quarantine purposes, a reliable method based on a PCR-RFLP
      procedure is reported. A DNA region containing mitochondrial NADH dehydrogenase
      genes was selected as a target sequence for the analysis. The amplification
      products (c. 1 kb) were digested with either SspI or DdeI, yielding specific
      patterns that differentiated each of the endemic species. Complete nucleotide
      sequences were determined, confirming empirical restriction maps. This report
      updates information on the geographical distribution of Rhagoletis species in
      Chile.

PMID- 12191443
TI  - Natural enemies of the maize cob borer, Mussidia nigrivenella (Lepidoptera:
      Pyralidae) in Benin, West Africa.
AB  - Mussidia nigrivenella Ragonot is a pest of maize cobs in West Africa. It
      significantly reduces maize yields and grain quality, with quantitative losses of
      2-25%at harvest, and up to 10-15% indirect losses due to an increase in storage
      pest infestation levels. Infestation by M. nigrivenella also significantly
      increased the susceptibility of maize to Aspergillus flavus infection and
      subsequent aflatoxin contamination. Surveys conducted in different agro
      ecological zones of Benin on cultivated and wild host plants during 1994-1997
      revealed one egg parasitoid, three larval parasitoids and one pupal parasitoid
      attacking M. nigrivenella. Egg parasitism was scarce on all host plants sampled
      and in all four agro-ecological zones. Parasitism by larval and pupal parasitoids
      was usually less than 10%, and varied with host plant species. Both larval and
      pupal parasitoids were rare or absent in cultivated maize fields. The solitary
      chalcidid pupal parasitoid, Antrocephalus crassipes Masi, was the predominant
      species, contributing approximately 53% of the observed mortality. Logistic
      regression analysis indicated that this parasitoid was more prevalent on fruits
      of Gardenia spp. (Rubiaceae) than on the other host plant species including maize
      used by M. nigrivenella, and was most abundant between February and September.
      The differences in parasitoid diversity and parasitism between Benin and other
      regions suggest that there are opportunities for biological control through
      introduction of exotic parasitoids or using the 'new association' approach, which
      uses natural enemies of closely related host species that occupy similar
      ecological niches to the target pest.

PMID- 12191444
TI  - Influence of temperature on pea aphid Acyrthosiphon pisum (Hemiptera: Aphididae)
      resistance to natural enemy attack.
AB  - The ability to resist or avoid natural enemy attack is a critically important
      insect life history trait, yet little is understood of how these traits may be
      affected by temperature. This study investigated how different genotypes of the
      pea aphid Acyrthosiphon pisum Harris, a pest of leguminous crops, varied in
      resistance to three different natural enemies (a fungal pathogen, two species of
      parasitoid wasp and a coccinellid beetle), and whether expression of resistance
      was influenced by temperature. Substantial clonal variation in resistance to the
      three natural enemies was found. Temperature influenced the number of aphids
      succumbing to the fungal pathogen Erynia neoaphidis Remaudiere & Hennebert, with
      resistance increasing at higher temperatures (18 vs. 28 degrees C). A temperature
      difference of 5 degrees C (18 vs. 23 degrees C) did not affect the ability of A.
      pisum to resist attack by the parasitoids Aphidius ervi Haliday and A. eadyi
      Stary, Gonzalez & Hall. Escape behaviour from foraging coccinellid beetles
      (Hippodamia convergens Guerin-Meneville) was not directly influenced by aphid
      clone or temperature (16 vs. 21 degrees C). However, there were significant
      interactions between clone and temperature (while most clones did not respond to
      temperature, one was less likely to escape at 16 degrees C), and between aphid
      clone and ladybird presence (some clones showed greater changes in escape
      behaviour in response to the presence of foraging coccinellids than others).
      Therefore, while larger temperature differences may alter interactions between
      Acyrthosiphon pisum and an entomopathogen, there is little evidence to suggest
      that smaller changes in temperature will alter pea aphid-natural enemy
      interactions.

PMID- 12191445
TI  - Identification of thrips species (Thysanoptera: Thripidae) on Japanese fruit
      trees by polymerase chain reaction and restriction fragment length polymorphism
      of the ribosomal ITS2 region.

PMID- 12191447
TI  - Maturing as a science: the New Perspectives in fMRI Research Award.

PMID- 12191448
TI  - Functional MRI and the study of human consciousness.
AB  - Functional brain imaging offers new opportunities for the study of that most
      pervasive of cognitive conditions, human consciousness. Since consciousness is
      attendant to so much of human cognitive life, its study requires secondary
      analysis of multiple experimental datasets. Here, four preprocessed datasets from
      the National fMRI Data Center are considered: Hazeltine et al., Neural activation
      during response competition; Ishai et al., The representation of objects in the
      human occipital and temporal cortex; Mechelli et al., The effects of presentation
      rate during word and pseudoword reading; and Postle et al., Activity in human
      frontal cortex associated with spatial working memory and saccadic behavior. The
      study of consciousness also draws from multiple disciplines. In this article, the
      philosophical subdiscipline of phenomenology provides initial characterization of
      phenomenal structures conceptually necessary for an analysis of consciousness.
      These structures include phenomenal intentionality, phenomenal superposition, and
      experienced temporality. The empirical predictions arising from these structures
      require new interpretive methods for their confirmation. These methods begin with
      single-subject (preprocessed) scan series, and consider the patterns of all
      voxels as potential multivariate encodings of phenomenal information. Twenty
      seven subjects from the four studies were analyzed with multivariate methods,
      revealing analogues of phenomenal structures, particularly the structures of
      temporality. In a second interpretive approach, artificial neural networks were
      used to detect a more explicit prediction from phenomenology, namely, that
      present experience contains and is inflected by past states of awareness and
      anticipated events. In all of 21 subjects in this analysis, nets were
      successfully trained to extract aspects of relative past and future brain states,
      in comparison with statistically similar controls. This exploratory study thus
      concludes that the proposed methods for "neurophenomenology" warrant further
      application, including the exploration of individual differences, multivariate
      differences between cognitive task conditions, and exploration of specific brain
      regions possibly contributing to the observations. All of these attractive
      questions, however, must be reserved for future research.

PMID- 12191449
TI  - Streams of consciousness.

PMID- 12191450
TI  - Focusing on the big picture with fMRI: consciousness and temporal flux.

PMID- 12191451
TI  - On having one's data shared.

PMID- 12191452
TI  - Intact motor imagery in chronic upper limb hemiplegics: evidence for activity
      independent action representations.
AB  - Four experiments were undertaken to examine the effects of chronic hemiplegia on
      the ability to internally represent actions involving either the paralyzed
      (contralesional) or relatively unaffected (ipsilesional) limb. An experimental
      group of chronic, densely hemiplegic patients was compared with controls who
      experienced nearly full recovery from an initially dense hemiparesis. All
      participants suffered cerebral vascular accidents that spared sites in premotor
      and parietal areas directly involved in representing upper limb actions. Despite
      chronic limb immobility, hemiplegic patients performed all four tasks at a high
      level of accuracy and showed no differences in their ability to represent actions
      of the contralesional versus ipsilesional limbs. On tasks that involved
      representing actions of the hands and lower arms, hemiplegic patients were as
      accurate as recovered controls. Hemiplegic patients were, however, less accurate
      than controls on a task that involved representing actions of either upper arm.
      Overall, chronic hemiplegics performed more accurately for decisions based on
      their contralesional limbs: a "hemiplegic advantage" that may be related to an
      ongoing focus on planning and/or imagining currently impossible movements. These
      findings reveal a dissociation between the ability to internally "represent"
      versus "produce" manual actions. Further, they demonstrate that internal action
      representations can be robust to even years of limb disuse.

PMID- 12191454
TI  - Separate influences of acoustic AM and FM sensitivity on the phonological
      decoding skills of impaired and normal readers.
AB  - Developmental dyslexia is associated with deficits in the processing of basic
      auditory stimuli. Yet it is unclear how these sensory impairments might
      contribute to poor reading skills. This study better characterizes the
      relationship between phonological decoding skills, the lack of which is generally
      accepted to comprise the core deficit in reading disabilities, and auditory
      sensitivity to amplitude modulation (AM) and frequency modulation (FM). Thirty
      eight adult subjects, 17 of whom had a history of developmental dyslexia,
      completed a battery of psychophysical measures of sensitivity to FM and AM at
      different modulation rates, along with a measure of pseudoword reading accuracy
      and standardized assessments of literacy and cognitive skills. The subjects with
      a history of dyslexia were significantly less sensitive than controls to 2-Hz FM
      and 20-Hz AM only. The absence of a significant group difference for 2-Hz AM
      shows that the dyslexics do not have a general deficit in detecting all slow
      modulations. Thresholds for detecting 2-Hz and 240-Hz FM and 20-Hz AM correlated
      significantly with pseudoword reading accuracy. After accounting for various
      cognitive skills, however, multiple regression analyses showed that detection
      thresholds for both 2-Hz FM and 20-Hz AM were significant and independent
      predictors of pseudoword reading ability in the entire sample. Thresholds for 2
      Hz AM and 240-Hz FM did not explain significant additional variance in pseudoword
      reading skill. It is therefore possible that certain components of auditory
      processing of modulations are related to phonological decoding skills, whereas
      others are not.

PMID- 12191453
TI  - A model of prefrontal cortex dopaminergic modulation during the delayed
      alternation task.
AB  - Working memory performance is modulated by the level of dopamine (DA) D1
      receptors stimulation in the prefrontal cortex (PFC). This modulation is exerted
      at different time scales. Injection of D1 agonists/antagonists exerts a long
      lasting influence (several minutes or hours) on PFC pyramidal neurons. In
      contrast, during performance of a cognitive task, the duration of the
      postsynaptic effect of phasic DA release is short lasting. The functional
      relationships of these two time scales of DA modulation remain poorly understood.
      Here we propose a model that combines these two time scales of DA modulation on a
      prefrontal neural network. The model links the cellular and behavioral levels
      during performance of the delayed alternation task. The network, which represents
      the activity of deep-layer pyramidal neurons with intrinsic neuronal properties,
      exhibits two stable states of activity that can be switched on and off by
      excitatory inputs from long-distance cortical areas arriving in superficial
      layers. These stable states allow PFC neurons to maintain representations during
      the delay period. The role of an increase of DA receptors stimulation is to
      restrict inputs arriving on the prefrontal network. The model explains how the
      level of working memory performance follows an inverted U-shape with an increased
      stimulation of DA D1 receptors. The model predicts that (1) D1 receptor agonists
      increase perseverations, (2) D1 antagonists increase distractability, and (3) the
      duration of the postsynaptic effect of phasic DA release in the PFC is adjusted
      to the delay period of the task. These results show how the precise duration of
      the postsynaptic effect of phasic DA release influences behavioral performance
      during a simple cognitive task.

PMID- 12191455
TI  - Testing memory for unseen visual stimuli in patients with extinction and spatial
      neglect.
AB  - Visual extinction after right parietal damage involves a loss of awareness for
      stimuli in the contralesional field when presented concurrently with ipsilesional
      stimuli, although contralesional stimuli are still perceived if presented alone.
      However, extinguished stimuli can still receive some residual on-line processing,
      without awareness. Here we examined whether such residual processing of
      extinguished stimuli can produce implicit and/or explicit memory traces lasting
      many minutes. We tested four patients with right parietal damage and left
      extinction on two sessions, each including distinct study and subsequent test
      phases. At study, pictures of objects were shown briefly in the right, left, or
      both fields. Patients were asked to name them without memory instructions
      (Session 1) or to make an indoor/outdoor categorization and memorize them
      (Session 2). They extinguished most left stimuli on bilateral presentation.
      During the test (up to 48 min later), fragmented pictures of the previously
      exposed objects (or novel objects) were presented alone in either field. Patients
      had to identify each object and then judge whether it had previously been
      exposed. Identification of fragmented pictures was better for previously exposed
      objects that had been consciously seen and critically also for objects that had
      been extinguished (as compared with novel objects), with no influence of the
      depth of processing during study. By contrast, explicit recollection occurred
      only for stimuli that were consciously seen at study and increased with depth of
      processing. These results suggest implicit but not explicit memory for
      extinguished visual stimuli in parietal patients.

PMID- 12191456
TI  - Hypnosis modulates activity in brain structures involved in the regulation of
      consciousness.
AB  - The notion of consciousness is at the core of an ongoing debate on the existence
      and nature of hypnotic states. Previously, we have described changes in brain
      activity associated with hypnosis (Rainville, Hofbauer, Paus, Duncan, Bushnell, &
      Price, 1999). Here, we replicate and extend those findings using positron
      emission tomography (PET) in 10 normal volunteers. Immediately after each of 8
      PET scans performed before (4 scans) and after (4 scans) the induction of
      hypnosis, subjects rated their perceived level of "mental relaxation" and "mental
      absorption," two of the key dimensions describing the experience of being
      hypnotized. Regression analyses between regional cerebral blood flow (rCBF) and
      self-ratings confirm the hypothesized involvement of the anterior cingulate
      cortex (ACC), the thalamus, and the ponto-mesencephalic brainstem in the
      production of hypnotic states. Hypnotic relaxation further involved an increase
      in occipital rCBF that is consistent with our previous interpretation that
      hypnotic states are characterized by a decrease in cortical arousal and a
      reduction in cross-modality suppression (disinhibition). In contrast, increases
      in mental absorption during hypnosis were associated with rCBF increases in a
      distributed network of cortical and subcortical structures previously described
      as the brain's attentional system. These findings are discussed in support of a
      state theory of hypnosis in which the basic changes in phenomenal experience
      produced by hypnotic induction reflect, at least in part, the modulation of
      activity within brain areas critically involved in the regulation of
      consciousness.

PMID- 12191457
TI  - Cerebellum and speech perception: a functional magnetic resonance imaging study.
AB  - A variety of data indicate that the cerebellum participates in perceptual tasks
      requiring the precise representation of temporal information. Access to the word
      form of a lexical item requires, among other functions, the processing of
      durational parameters of verbal utterances. Therefore, cerebellar dysfunctions
      must be expected to impair word recognition. In order to specify the topography
      of the assumed cerebellar speech perception mechanism, a functional magnetic
      resonance imaging study was performed using the German lexical items "Boden"
      ([bodn], Engl. "floor") and "Boten" ([botn], "messengers") as test materials. The
      contrast in sound structure of these two lexical items can be signaled either by
      the length of the wordmedial pause (closure time, CLT; an exclusively temporal
      measure) or by the aspiration noise of wordmedial "d" or "t" (voice onset time,
      VOT; an intrasegmental cue). A previous study found bilateral cerebellar
      disorders to compromise word recognition based on CLT whereas the encoding of VOT
      remained unimpaired. In the present study, two series of "Boden - Boten"
      utterances were resynthesized, systematically varying either in CLT or VOT.
      Subjects had to identify both words "Boden" and "Boten" by analysis of either the
      durational parameter CLT or the VOT aspiration segment. In a subtraction design,
      CLT categorization as compared to VOT identification (CLT - VOT) yielded a
      significant hemodynamic response of the right cerebellar hemisphere
      (neocerebellum Crus I) and the frontal lobe (anterior to Broca's area). The
      reversed contrast ( VOT - CLT) resulted in a single activation cluster located at
      the level of the supratemporal plane of the dominant hemisphere. These findings
      provide first evidence for a distinct contribution of the right cerebellar
      hemisphere to speech perception in terms of encoding of durational parameters of
      verbal utterances. Verbal working memory tasks, lexical response selection, and
      auditory imagery of word strings have been reported to elicit activation clusters
      of a similar location. Conceivably, representation of the temporal structure of
      speech sound sequences represents the common denominator of cerebellar
      participation in cognitive tasks acting on a phonetic code.

PMID- 12191458
TI  - Modulation of amygdalar activity by the conscious regulation of negative emotion.
AB  - Lesion and neuroimaging studies suggest the amygdala is important in the
      perception and production of negative emotion; however, the effects of emotion
      regulation on the amygdalar response to negative stimuli remain unknown. Using
      event-related fMRI, we tested the hypothesis that voluntary modulation of
      negative emotion is associated with changes in neural activity within the
      amygdala. Negative and neutral pictures were presented with instructions to
      either "maintain" the emotional response or "passively view" the picture without
      regulating the emotion. Each picture presentation was followed by a delay, after
      which subjects indicated how they currently felt via a response keypad.
      Consistent with previous reports, greater signal change was observed in the
      amygdala during the presentation of negative compared to neutral pictures. No
      significant effect of instruction was found during the picture presentation
      component of the trial. However, a prolonged increase in signal change was
      observed in the amygdala when subjects maintained the negative emotional response
      during the delay following negative picture offset. This increase in amygdalar
      signal due to the active maintenance of negative emotion was significantly
      correlated with subjects' self-reported dispositional levels of negative affect.
      These results suggest that consciously evoked cognitive mechanisms that alter the
      emotional response of the subject operate, at least in part, by altering the
      degree of neural activity within the amygdala.

PMID- 12191459
TI  - Neural basis of the retrieval of people's names: evidence from brain-damaged
      patients and fMRI.
AB  - The aim of this study was to identify the neuroanatomical basis of the retrieval
      of people's names. Lesion data showed that patients with language-dominant
      temporal lobectomy had impairments in their ability to retrieve familiar and
      newly learned people's names, whereas patients with language-nondominant temporal
      lobectomy had difficulty retrieving newly learned people's names. Functional
      magnetic resonance imaging experiments revealed activations in the left temporal
      polar region during the retrieval of familiar and newly learned people's names,
      and in the right superior temporal and bilateral prefrontal cortices during the
      retrieval of newly learned information from face cues. These data provide new
      evidence that the left anterior temporal region is crucial for the retrieval of
      people's names irrespective of their familiarity and that the right superior
      temporal and bilateral prefrontal areas are crucial for the process of
      associating newly learned people's faces and names.

PMID- 12191460
TI  - An electrophysiological study of the effects of orthographic neighborhood size on
      printed word perception.
AB  - In two experiments participants read words and pseudowords that belonged to
      either large or small lexical neighborhoods while event-related brain potentials
      (ERPs) were recorded from their scalps. In Experiment 1, participants made
      speeded lexical decisions to all items, while in Experiment 2 they engaged in a
      go/no-go semantic categorization task in which the critical items did not require
      an overt behavioral response. In both experiments, words and pseudowords produced
      a consistent pattern of ERP effects: items with many lexical neighbors (large
      neighborhoods) generated larger N400s than similar items with relatively fewer
      lexical neighbors (small neighborhoods). Reaction time (RT, Experiment 1), on the
      other hand, showed a different pattern consistent with previous behavioral
      studies. While words tended to produce a facilitation in RT for larger
      neighborhoods, pseudowords produced an inhibition effect. The findings are
      discussed in terms of recent theories of word recognition and the functional
      significance of the N400.

PMID- 12191461
TI  - Exploring the activation of semantic and phonological codes during speech
      planning with event-related brain potentials.
AB  - We present a new technique for studying the activation of semantic and
      phonological codes in speech planning using event-related brain potentials (ERPs)
      that extend a well-established behavioral procedure from speech production
      research. It combines a delayed picture-naming task with a priming procedure.
      While participants prepared the production of a depicted object's name, they
      heard an auditory target word. If the prepared picture name and the target word
      were semantically or phonologically related, the ERP waveform to the target word
      tended less towards the negative when compared to an unrelated control. These
      effects were widely distributed. By contrast, if participants performed a
      nonlinguistic task on the depicted object (natural size judgment), the semantic
      effect was still obtained while the phonological effect disappeared. This
      suggests that the former effect indexes semantic activation involved in object
      processing while the latter effect indexes word-form activation specific to
      lexical processing. The data are discussed in the context of models of lexical
      access in speech production.

PMID- 12191462
TI  - Functional MRI in the awake monkey: the missing link.

PMID- 12191463
TI  - An ESCRT into the endosome.
AB  - Multivesicular endosomes sort ubiquitinated membrane proteins for degradation by
      incorporating them into inwardly budding vesicles. The recent identification of
      two new oligomeric components of the sorting machinery gives us a detailed view
      of the complex protein-protein interactions driving this process.

PMID- 12191464
TI  - Candida albicans switches mates.
AB  - The "asexual" human fungal pathogen Candida albicans has recently been engineered
      to be able to mate. A paper in the August 9, 2002 issue of Cell shows that mating
      competence is increased dramatically when mating partners are in a rare switch
      variant cell type that does not normally occur at body temperature.

PMID- 12191465
TI  - All signaling is local?
AB  - The mechanism of signal transmission following ligand stimulation of receptor
      tyrosine kinases in living cells is poorly understood. Recent studies have
      visualized the spatio-temporal pattern of EGF signaling, indicating that receptor
      density is an important factor in the mechanism of lateral propagation of local
      EGF signaling.

PMID- 12191466
TI  - Desperately seeking...something.
AB  - Published online this week in Structure, Wisely et al. present a high-resolution
      X-ray crystallographic structure of the ligand binding domain of human hepatocyte
      nuclear factor 4 gamma (HNF4gamma). They find fatty acids filling the ligand
      binding pocket of this receptor long considered an orphan, but these "ligands"
      appear to be locked into the protein and not readily amenable to exchange. Not
      only does this present a new paradigm for nuclear receptors but it also provides
      new insights into their evolutionary origins.

PMID- 12191467
TI  - Cleave to leave: structural insights into the dynamic organization of the nuclear
      pore complex.
AB  - A detailed understanding of the fine structure of the nuclear pore complex has
      remained elusive. Now, studies on a small protein domain have shed light on the
      dynamic organization of this massive assembly.

PMID- 12191468
TI  - Huntingtin fragments that aggregate go their separate ways.
AB  - N-terminal region of mutant huntingtin forms intranuclear and cytoplasmic
      aggregates in neurons that may contribute to neuronal death in Huntington's
      disease. show that different endoprotease-cleaved huntingtin fragments form
      nuclear and cytoplasmic inclusions.

PMID- 12191469
TI  - Ordered recruitment: gene-specific mechanism of transcription activation.
AB  - Activators, chromatin-modifying enzymes, and basal transcription factors unite to
      activate genes, but are recruited in a precise order to promoters. The timing of
      the activation of transcription and the ordered recruitment of factors to
      promoters are the engines which, at the right moment and for the right length of
      time, drive the transcriptional regulation of each gene throughout the life of a
      cell.

PMID- 12191470
TI  - Cholesterol addition to ER membranes alters conformation of SCAP, the SREBP
      escort protein that regulates cholesterol metabolism.
AB  - Sterol accumulation in membranes blocks the exit of SCAP from the ER, preventing
      SREBP cleavage and reducing cholesterol synthesis. Sterols act through SCAP's
      sterol-sensing domain by an obscure mechanism. Here, we show that addition of
      cholesterol to ER membranes in vitro causes a conformational change in SCAP,
      detected by the unmasking of closely spaced trypsin cleavage sites. Two mutant
      forms of SCAP (Y298C and D443N) that are refractory to sterol regulation in vivo
      are also refractory to sterol-induced conformational change in vitro. 25
      hydroxycholesterol, a potent regulator of SCAP in vivo, fails to change SCAP's
      conformation in vitro, suggesting that oxysterols act in intact cells by
      translocating cholesterol from plasma membrane to ER. These studies demonstrate
      an in vitro effect of cholesterol on the sterol regulatory machinery.

PMID- 12191471
TI  - Phosphorylation by protein kinase CK2: a signaling switch for the caspase
      inhibiting protein ARC.
AB  - Caspases play a central role in apoptosis, but their activity is under the
      control of caspase-inhibiting proteins. A characteristic of caspase-inhibiting
      proteins is direct caspase binding. It is yet unknown how the localization of
      caspase-inhibiting proteins is regulated and whether there are upstream signals
      controlling their function. Here we report that the function of ARC is regulated
      by protein kinase CK2. ARC at threonine 149 is phosphorylated by CK2. This
      phosphorylation targets ARC to mitochondria. ARC is able to bind to caspase-8
      only when it is localized to mitochondria but not to the cytoplasm. Our results
      reveal a molecular mechanism by which a caspase-inhibiting protein requires
      phosphorylation in order to prevent apoptosis.

PMID- 12191472
TI  - Proteases acting on mutant huntingtin generate cleaved products that
      differentially build up cytoplasmic and nuclear inclusions.
AB  - Proteolytic processing of mutant huntingtin (mhtt) is regarded as a key event in
      the pathogenesis of Huntington's disease (HD). Mhtt fragments containing a
      polyglutamine expansion form intracellular inclusions and are more cytotoxic than
      full-length mhtt. Here, we report that two distinct mhtt fragments, termed cp-A
      and cp-B, differentially build up nuclear and cytoplasmic inclusions in HD brain
      and in a cellular model for HD. Cp-A is released by cleavage of htt in a 10 amino
      acid domain and is the major fragment that aggregates in the nucleus.
      Furthermore, we provide evidence that cp-A and cp-B are most likely generated by
      aspartic endopeptidases acting in concert with the proteasome to ensure the
      normal turnover of htt. These proteolytic processes are thus potential targets
      for therapeutic intervention in HD.

PMID- 12191473
TI  - Smad2 nucleocytoplasmic shuttling by nucleoporins CAN/Nup214 and Nup153 feeds
      TGFbeta signaling complexes in the cytoplasm and nucleus.
AB  - The transcription factor Smad2 is released from cytoplasmic retention by TGFbeta
      receptor-mediated phosphorylation, accumulating in the nucleus where it
      associates with cofactors to regulate transcription. We uncovered direct
      interactions of Smad2 with the nucleoporins CAN/Nup214 and Nup153. These
      interactions mediate constitutive nucleocytoplasmic shuttling of Smad2.
      CAN/Nup214 and Nup153 compete with the cytoplasmic retention factor SARA and the
      nuclear Smad2 partner FAST-1 for binding to a hydrophobic corridor on the MH2
      surface of Smad2. TGFbeta receptor-mediated phosphorylation stimulates nuclear
      accumulation of Smad2 by modifying its affinity for SARA and Smad4 but not for
      CAN/Nup214 or Nup153. Thus, by directly contacting the nuclear pore complex,
      Smad2 undergoes constant shuttling, providing a dynamic pool that is
      competitively drawn by cytoplasmic and nuclear signal transduction partners.

PMID- 12191474
TI  - Nucleocytoplasmic shuttling of Smads 2, 3, and 4 permits sensing of TGF-beta
      receptor activity.
AB  - Transforming growth factor (TGF)-beta stimulation leads to phosphorylation and
      activation of Smad2 and Smad3, which form complexes with Smad4 that accumulate in
      the nucleus and regulate transcription of target genes. Here we demonstrate that,
      following TGF-beta stimulation of epithelial cells, receptors remain active for
      at least 3-4 hr, and continuous receptor activity is required to maintain active
      Smads in the nucleus and for TGF-beta-induced transcription. We show that
      continuous nucleocytoplasmic shuttling of the Smads during active TGF-beta
      signaling provides the mechanism whereby the intracellular transducers of the
      signal continuously monitor receptor activity. Our data therefore explain how, at
      all times, the concentration of active Smads in the nucleus is directly dictated
      by the levels of activated receptors in the cytoplasm.

PMID- 12191475
TI  - X-ray crystal structure and functional analysis of vaccinia virus K3L reveals
      molecular determinants for PKR subversion and substrate recognition.
AB  - The vaccinia virus protein K3L subverts the mammalian antiviral defense mechanism
      by inhibiting the RNA-dependent protein kinase PKR. K3L is a structural mimic of
      PKR's natural substrate, the translation initiation factor eIF2alpha. To further
      our understanding of K3L inhibitory function and PKR substrate recognition, we
      have solved the 1.8 A X-ray crystal structure of K3L. The structure consists of a
      five-strand beta barrel with an intervening helix insert region similar in
      topology to the functionally divergent S1 domain. Mutational analysis identifies
      two proximal regions of the K3L structure as possessing specialized PKR binding
      and inhibitory function. Further analysis reveals that PKR dimerization composes
      a key switch that regulates both its catalytic activation and its molecular
      recognition of K3L and eIF2alpha.

PMID- 12191476
TI  - The assembly of Ebola virus nucleocapsid requires virion-associated proteins 35
      and 24 and posttranslational modification of nucleoprotein.
AB  - Ebola virus encodes seven viral structural and regulatory proteins that support
      its high rates of replication, but little is known about nucleocapsid assembly of
      this virus in infected cells. We report here that three viral proteins are
      necessary and sufficient for formation of Ebola virus particles and that
      intracellular posttranslational modification regulates this process. Expression
      of the nucleoprotein (NP) and virion-associated proteins VP35 and VP24 led to
      spontaneous assembly of nucleocapsids in transfected 293T cells by transmission
      electron microscopy. A specific biochemical interaction of these three proteins
      was demonstrated, and, interestingly, O-glycosylation and sialation of NP were
      demonstrated and necessary for their association. This distinct mechanism of
      regulation for filovirus assembly suggests new approaches for viral therapies and
      vaccines for Ebola and related viruses.

PMID- 12191477
TI  - The concerted conformational changes during human rhinovirus 2 uncoating.
AB  - Delivery of the rhinovirus genome into the cytoplasm involves a cooperative
      structural modification of the viral capsid. We have studied this phenomenon for
      human rhinovirus serotype 2 (HRV2). The structure of the empty capsid has been
      determined to a resolution of better than 15 A by cryo-electron microscopy, and
      the atomic structure of native HRV2 was used to examine conformational changes of
      the capsid. The two proteins around the 5-fold axes make an iris type of movement
      to open a 10 A diameter channel which allows the RNA genome to exit, and the N
      terminus of VP1 exits the capsid at the pseudo 3-fold axis. A remarkable
      modification occurs at the 2-fold axes where the N-terminal loop of VP2 bends
      inward, probably to detach the RNA.

PMID- 12191478
TI  - Structural unity among viral origin binding proteins: crystal structure of the
      nuclease domain of adeno-associated virus Rep.
AB  - Adeno-associated virus (AAV), unique among animal viruses in its ability to
      integrate into a specific chromosomal location, is a promising vector for human
      gene therapy. AAV Replication (Rep) protein is essential for viral replication
      and integration, and its amino terminal domain possesses site-specific DNA
      binding and endonuclease activities required for replication initiation and
      integration. This domain displays a novel endonuclease fold and demonstrates an
      unexpected structural relationship to other viral origin binding proteins such as
      the papillomavirus E1 protein and the SV40 T antigen. The active site, located at
      the bottom of a positively charged cleft, is formed by the spatial convergence of
      a divalent metal ion and two conserved sequence motifs that define the rolling
      circle replication superfamily.

PMID- 12191479
TI  - Important contribution to catalysis of peptide bond formation by a single
      ionizing group within the ribosome.
AB  - The catalytic mechanism of peptide bond formation on the ribosome is not known.
      The crystal structure of 50S ribosomal subunits shows that the catalytic center
      consists of RNA only and suggests potential catalytic residues. Here we report
      rapid kinetics of the peptidyl transferase reaction with puromycin at rates up to
      50 s(-1). The rate-pH profile of the reaction reveals that protonation of a
      single ribosomal residue (pK(a) = 7.5), in addition to protonation of the
      nucleophilic amino group, strongly inhibits the reaction (>100-fold). The A2451U
      mutation within the peptidyl transferase center has about the same inhibitory
      effect. These results suggest a contribution to overall catalysis of general acid
      base and/or conformational catalysis involving an ionizing group at the active
      site.

PMID- 12191480
TI  - The three-dimensional structure of the autoproteolytic, nuclear pore-targeting
      domain of the human nucleoporin Nup98.
AB  - Nup98 is a component of the nuclear pore that plays its primary role in the
      export of RNAs. Nup98 is expressed in two forms, derived from alternate mRNA
      splicing. Both forms are processed into two peptides through autoproteolysis
      mediated by the C-terminal domain of hNup98. The three-dimensional structure of
      the C-terminal domain reveals a novel protein fold, and thus a new class of
      autocatalytic proteases. The structure further reveals that the suggested
      nucleoporin RNA binding motif is unlikely to bind to RNA. The C terminus also
      contains sequences that target hNup98 to the nuclear pore complex. Noncovalent
      interactions between the C-terminal domain and the cleaved peptide tail are
      visible and suggest a model for cleavage-dependent targeting of hNup98 to the
      nuclear pore.

PMID- 12191481
TI  - Crystal structure of the homologous-pairing domain from the human Rad52
      recombinase in the undecameric form.
AB  - The human Rad52 protein forms a heptameric ring that catalyzes homologous
      pairing. The N-terminal half of Rad52 is the catalytic domain for homologous
      pairing, and the ring formed by the domain fragment was reported to be
      approximately decameric. Splicing variants of Rad52 and a yeast homolog (Rad59)
      are composed mostly of this domain. In this study, we determined the crystal
      structure of the homologous-pairing domain of human Rad52 and revealed that the
      domain forms an undecameric ring. Each monomer has a beta-beta-beta-alpha fold,
      which consists of highly conserved amino acid residues among Rad52 homologs. A
      mutational analysis revealed that the amino acid residues located between the
      beta-beta-beta-alpha fold and the characteristic hairpin loop are essential for
      ssDNA and dsDNA binding.

PMID- 12191483
TI  - XRCC3 controls the fidelity of homologous recombination: roles for XRCC3 in late
      stages of recombination.
AB  - XRCC3 is a RAD51 paralog that functions in the repair of DNA double-strand breaks
      (DSBs) by homologous recombination (HR). XRCC3 mutation causes severe chromosome
      instability. We find that XRCC3 mutant cells display radically altered HR product
      spectra, with increased gene conversion tract lengths, increased frequencies of
      discontinuous tracts, and frequent local rearrangements associated with HR. These
      results indicate that XRCC3 function is not limited to HR initiation, but extends
      to later stages in formation and resolution of HR intermediates, possibly by
      stabilizing heteroduplex DNA. The results further demonstrate that HR defects can
      promote genomic instability not only through failure to initiate HR (leading to
      nonhomologous repair) but also through aberrant processing of HR intermediates.
      Both mechanisms may contribute to carcinogenesis in HR-deficient cells.

PMID- 12191482
TI  - Recovery from checkpoint-mediated arrest after repair of a double-strand break
      requires Srs2 helicase.
AB  - In Saccharomyces strains in which homologous recombination is delayed
      sufficiently to activate the DNA damage checkpoint, Rad53p checkpoint kinase
      activity appears 1 hr after DSB induction and disappears soon after completion of
      repair. Cells lacking Srs2p helicase fail to recover even though they apparently
      complete DNA repair; Rad53p kinase remains activated. srs2Delta cells also fail
      to adapt when DSB repair is prevented. The recovery defect of srs2Delta is
      suppressed in mec1Delta strains lacking the checkpoint or when DSB repair occurs
      before checkpoint activation. Permanent preanaphase arrest of srs2Delta cells is
      reversed by the addition of caffeine after cells have arrested. Thus, in addition
      to its roles in recombination, Srs2p appears to be needed to turn off the DNA
      damage checkpoint.

PMID- 12191484
TI  - POU/TBP cooperativity: a mechanism for enhancer action from a distance.
AB  - Enhancers when functioning at a distance cannot effectively stimulate
      transcription from core promoters. We demonstrate that this is due to the
      inability of enhancer-bound activators to recruit TBP to a distal TATA box.
      Surprisingly, binding of a transcriptionally inert Oct-1 POU domain near a core
      promoter enables an enhancer to function from a distance. POU activity neither
      requires the coactivator OCA-B nor the interaction of TBP with TFIIA. Instead,
      the POU domain directly facilitates TBP recruitment to the promoter utilizing a
      bipartite interaction surface. These results establish that an interaction
      between the DNA binding domain of an activator and TBP can be used to stimulate
      transcription. Furthermore, they suggest a mechanism for long-range enhancer
      function in which a TBP complex is preassembled on a promoter via localized
      recruitment and then acted upon by distal activators.

PMID- 12191485
TI  - Structure of the yeast RNA polymerase II holoenzyme: Mediator conformation and
      polymerase interaction.
AB  - The holoenzyme formed by RNA polymerase II (RNAPII) and the Mediator complex is
      the target of transcriptional regulators in vivo. A three-dimensional structure
      of the yeast holoenzyme has been generated from electron microscopic images of
      single holoenzyme particles. Extensive changes in Mediator conformation required
      for interaction with RNAPII have been modeled by correlating the polymerase-bound
      and free Mediator structures. Determination of the precise orientation of the
      RNAPII in the holoenzyme indicates that Mediator contacts are centered on the
      RNAPII Rpb3/Rpb11 heterodimer, the eukaryotic homolog of the alpha(2) homodimer
      involved in transcription regulation in prokaryotes. Implications for the
      possible mechanism of transcription regulation by Mediator are discussed.

PMID- 12191486
TI  - The inflammasome: a molecular platform triggering activation of inflammatory
      caspases and processing of proIL-beta.
AB  - Generation of Interleukin (IL)-1beta via cleavage of its proform requires the
      activity of caspase-1 (and caspase-11 in mice), but the mechanism involved in the
      activation of the proinflammatory caspases remains elusive. Here we report the
      identification of a caspase-activating complex that we call the inflammasome. The
      inflammasome comprises caspase-1, caspase-5, Pycard/Asc, and NALP1, a Pyrin
      domain-containing protein sharing structural homology with NODs. Using a cell
      free system, we show that proinflammatory caspase activation and proIL-1beta
      processing is lost upon prior immunodepletion of Pycard. Moreover, expression of
      a dominant-negative form of Pycard in differentiated THP-1 cells blocks proIL
      1beta maturation and activation of inflammatory caspases induced by LPS in vivo.
      Thus, the inflammasome constitutes an important arm of the innate immunity.

PMID- 12191487
TI  - ParB-stimulated nucleotide exchange regulates a switch in functionally distinct
      ParA activities.
AB  - ParA and ParB of Caulobacter crescentus belong to a conserved family of bacterial
      proteins implicated in chromosome segregation. ParB binds to DNA sequences
      adjacent to the origin of replication and localizes to opposite cell poles
      shortly following the initiation of DNA replication. ParA has homology to a
      conserved and widespread family of ATPases. Here, we show that ParB regulates the
      ParA ATPase activity by promoting nucleotide exchange in a fashion reminiscent of
      the exchange factors of eukaryotic G proteins. Furthermore, we demonstrate that
      ADP-bound ParA binds single-stranded DNA, whereas the ATP-bound form dissociates
      ParB from its DNA binding sites. Increasing the fraction of ParA-ADP in the cell
      inhibits cell division, suggesting that this simple nucleotide switch may
      regulate cytokinesis.

PMID- 12191488
TI  - Central nitric oxide regulation of the hypothalamic-pituitary-adrenocortical axis
      in adult male rats.
AB  - The presence of nitric oxide (NO) synthase (NOS) in hypothalamic structures which
      control the activity of the pituitary-adrenocortical axis suggests that NO might
      be involved in the central regulation of ACTH secretion. We have studied the
      involvement of NO in the activity of the hypopothalamic-pituitary-adrenocortical
      (HPA) axis in intact and adrenalectomized rats. The acute effects (4 h) of two
      NOS inhibitors (HP-228 and NMMA), injected into the left lateral cerebral
      ventricle of freely moving male rats, on hypothalamic CRH and pituitary
      proopiomelacortin (POMC) mRNA levels as well as ACTH plasma levels were
      evaluated. In intact rats, HP-228, but not NMMA, induced an increase in CRH mRNA
      levels, while in adrenalectomized animals, both NOS inhibitors were effective in
      increasing CRH mRNA. In intact and adrenalectomized rats, both NOS inhibitors
      induced an increase in anterior pituitary POMC mRNA levels. Plasma ACTH levels
      were significantly elevated from 30 min to 2 h following the administration of
      either HP-228 or NMMA. In adrenalectomized animals, both NOS inhibitors produced
      a much striking increase of plasma ACTH levels which were still significantly
      increased at the longest time-interval studied. These results suggest that the
      central NO system exerts a tonic negative influence on the activity of the HPA
      axis in the presence or absence of circulating glucocorticoids.

PMID- 12191489
TI  - Elevated arylalkylamine-N-acetyltransferase (AA-NAT) gene expression in medial
      habenular and suprachiasmatic nuclei of hibernating ground squirrels.
AB  - Hibernation, an adaptive response for energy conservation in mammals, involves a
      variety of physiological changes. Melatonin is linked with the regulation of core
      body temperature and intervenes in generating circadian cycles; its role in
      seasonal (circannual) rhythms of hibernation is explored here. Melatonin is
      primarily produced in the pineal gland. Since arylalkylamine-N-acetyltransferase
      (AA-NAT) is the rate-limiting enzyme for synthesizing melatonin, AA-NAT gene
      expression was investigated to assess the possible role of melatonin in
      hibernation. The findings presented here utilized combined in situ hybridization
      and immunohistochemistry methodologies to evaluate the AA-NAT mRNA expression in
      brains of both hibernating and non-hibernating ground squirrels. Brains were
      examined for the expression of AA-NAT mRNA using a oligonucleotide AA-NAT probe;
      antibody against neurofilament-70 (NF-70) was used as a neuronal marker. All
      hibernating animals expressed significantly (P<0.01) elevated levels of AA-NAT
      mRNA in both the epithalamic medial habenular nuclei (MHb) area and the
      hypothalamic suprachiasmatic nuclei (SCN), which is also known as the master
      biologic clock. These findings represent the first demonstration of the
      expression of mRNA encoding for AA-NAT in the extra-pineal (i.e. SCN and MHb)
      sites of thirteen-lined ground squirrels and indicate that the habenular nucleus
      may be an important supplementary location for melatonin biosynthesis. The data
      presented here indicate that AA-NAT gene is one of the few specific genes up
      regulated during hibernation and suggest that elevation of its expression in SCN
      and MHb may play an essential role in the generation and maintenance of
      hibernation.

PMID- 12191490
TI  - Cloning of two transcripts, HKT4.1a and HKT4.1b, from the human two-pore K+
      channel gene KCNK4. Chromosomal localization, tissue distribution and functional
      expression.
AB  - The human KCNK4 gene encodes several transcripts that generate two-pore K+
      channel subunits. We describe the identification and cloning of two transcripts
      of this gene: human KT4.1a (HKT4.1a) and HKT4.1b. They encode proteins of 393 and
      419 amino acids, respectively. HKT4.1a and mouse TRAAK (mTRAAK) are 83%
      identical, polymerase chain reaction (PCR) experiments performed with rat and
      human samples as well as the comparison of the HKT4.1 and mTRAAK UTRs strongly
      suggest that both the human and mouse cDNAs are products of ortholog genes. In
      contrast to the reported exclusive expression mTRAAK in the nervous system, human
      and rat KCNK4 gene products are expressed widely in several tissues. Northern
      blot analysis revealed the presence of three bands of 1.9, 3.0, and 4.8 kb in
      human, while in rat four bands of 1.8, 3.6, 5.2 and 8.6 kb were observed. Human
      KCNK4 transcripts were expressed mainly in the heart and brain but also in the
      liver, skeletal muscle, kidney and pancreas. In rat, the transcripts were
      strongly expressed in the brain but were also detected in the lung, kidney,
      liver, spleen, skeletal muscle, testes and at lower levels in the heart.
      Expression of HKT4.1b in Xenopus oocytes drives the resting potential close to
      the potassium equilibrium voltage. The expressed channels are not gated by
      voltage and are permanently open. The channels are not blocked by the classical
      K+ channel blockers TEA, 4-AP, Cs+, Ba++, quinine or quinidine. Analysis of
      genomic sequences reveals that seven exons participate to produce HKT4.1a and 11
      exons to produce HKT4.1b cDNAs. The KCNK4 gene maps to chromosome 11q13.

PMID- 12191491
TI  - Differential expression of multiple calmodulin genes in cells of the white matter
      of the rat spinal cord.
AB  - Calmodulin (CaM) displays complex cytoplasmic and synaptic functions in the
      nervous system. However, the very little information that is available on the
      gene expression of the multiple CaM genes in different glial cell types are from
      brain tissues of rodents, and no data have been published on their CaM gene
      expression in the spinal cord. Therefore, we have modified and tested a color in
      situ hybridization method sensitive enough to detect mRNA populations in cells
      with low CaM mRNA abundances in the white matter of the rat lumbar spinal cord.
      Morphologically, two distinct cell types expressing CaM mRNAs were detected.
      Differential CaM gene expression was demonstrated in medium-sized astrocyte-like
      cells that reside predominantly in the dorsal column of the spinal cord, where
      CaM I mRNA was most abundant, followed by the CaM III and CaM II mRNA
      populations. The oligodendrocytes displayed a less differential CaM gene
      expression in both the dorsal and the lateral columns, but the CaM I gene had a
      slightly higher expression level than those of the other CaM genes. The results
      indicate that the CaM gene expression profile of the spinal cord is richer and
      more complex than previously thought on the basis of conventional radioactive in
      situ hybridization techniques. Thus, when a method that is sufficiently sensitive
      was used, more cell types could be demonstrated to express CaM mRNAs; hence, in
      spite of their lower CaM expression, glial cells could also be visualized.

PMID- 12191492
TI  - Characterization of a repressor element in the promoter region of proprotein
      convertase 2 (PC2) gene.
AB  - The proprotein convertase PC2 is primarily expressed in neuroendocrine cells
      where it mediates the proteolytic maturation of prohormones and proneuropeptides.
      We have identified in the upstream sequence of its gene a conserved domain
      partially homologous to the repressor element RE1/NRSE found in several genes for
      neuronal proteins. RE1/NRSE binds the silencing transcription factor REST/NRSF, a
      nuclear protein primarily found in nonneuronal cells. To determine the
      functionality of the PC2 gene RE1-like sequence (RE1-lk), we examined by
      electrophoretic mobility shift assays its ability to attach nuclear factors from
      PC2-expressing and nonexpressing cells. Specific binding factors were mostly
      detectable in PC2-non-expressing cells. These factors differ from REST/NRSF, as
      molar excess of competing RE1/NRSE could not prevent their binding to RE1-lk.
      Reciprocally, molar excess of RE1-lk could not prevent the binding of RE1/NRSE to
      the DNA-binding domain of a recombinant REST/NRSF. The presence of RE1-lk in cis
      reduced the ability of the PC2 promoter and the heterologous phosphoglycerate
      kinase promoter to drive expression of a green fluorescent protein reporter gene
      in transiently transfected PC2-nonexpressing cells, but not in PC2-expressing
      cells. These observations suggest that binding of transcription-silencing factors
      to the RE1-lk element may contribute to repression of the PC2 gene in
      nonneuroendocrine cells.

PMID- 12191493
TI  - Estradiol enhances Akt activation in cortical explant cultures following neuronal
      injury.
AB  - We have previously demonstrated that estradiol reduces cell death in cortical
      explant cultures following injury induced by metabolic inhibition in a receptor
      dependent fashion. In this study, we examined whether cell death involves
      apoptosis and assessed the potential mediators of estradiol's actions. Cortical
      explant cultures were generated from postnatal day 3 rat pups. On day 7 in vitro,
      explants were injured by exposure to 1 mM 2-DG/2 mM KCN for 2 h to model the
      metabolic inhibition observed during ischemia. Explants were fixed in 4%
      paraformaldehyde at 2, 6, 10 and 24 h following the injury period and 18-microm
      thick sections were cut on a cryostat and stained with cresyl violet to assess
      cell death. The same sections were also labeled by TUNEL to determine whether
      cell death occurred by apoptosis. Other sections were used for
      immunohistochemistry to determine whether cells that stained positive for
      activated caspase 3 were also immunopositive for NeuN, a neuronal marker, or
      GFAP, an astrocyte marker. Protein was extracted for Western blot analysis from a
      separate set of explants collected at 0, 0.5, 1, 2 and 4 h following the
      conclusion of the injury. Estradiol treatment significantly reduced the number of
      cells undergoing apoptotic cell death as indicated by nuclear condensation
      visualized by cresyl violet staining (P<0.05). TUNEL staining revealed that the
      majority of pyknotic and fragmented nuclei were also TUNEL positive. Furthermore,
      caspase 3 activation appeared to be restricted to neurons. To examine a possible
      mechanism by which estradiol prevents apoptosis, we examined the level of
      activation of Akt kinase, which mediates antiapoptotic signals. Potential
      activation was measured by phosphorylation of Akt at Ser473 by Western blot
      analysis. In the absence of estradiol, pAkt levels were significantly increased
      at 2 h following the termination of injury. Explants that were pretreated with
      estradiol exhibited elevated levels of pAkt at 1 h following injury. Treatment
      with ICI 182,780 prevented the effect of estradiol. These studies suggest that
      estradiol prevents injury-induced apoptosis and that Akt activation may mediate
      these protective effects.

PMID- 12191494
TI  - Immunohistochemical localization of N-methyl-D-aspartate receptor subunits in the
      adult murine hippocampal formation: evidence for a unique role of the NR2D
      subunit.
AB  - NMDA receptors were immunopurified from adult mouse forebrain and screened by
      immunoblotting. NR1 was co-associated with NR2A, NR2B and NR2D but not NR2C, nor
      was NR2C detected in adult mouse hippocampal membranes. The anatomical
      distribution of NR1, 2A, 2B and 2D was mapped in the adult murine hippocampal
      formation. NR1-like immunoreactivity was localised to cell bodies of pyramidal
      neurons, granule cells and hilar cells of the dentate gyrus. Apical dendrites of
      the CA subfields and hilar cells were also immunopositive. NR2A- and NR2B-like
      immunoreactivity essentially co-localised with that of NR1 implying co-assembly
      of all three subunits in this brain structure. NR2D-like immunoreactivity was
      distinct, being totally excluded from pyramidal, granule and hilar cell bodies.
      Strong, punctate staining was restricted to the oriens layer of CA1 and the
      stratum lucidum of CA3 consistent with labelling of presynaptic receptors. Less
      intense staining was also observed in the internal third of the molecular layer
      of the dentate gyrus.

PMID- 12191495
TI  - Muscarine enhances soluble amyloid precursor protein secretion in human
      neuroblastoma SH-SY5Y by a pathway dependent on protein kinase C(alpha), src
      tyrosine kinase and extracellular signal-regulated kinase but not phospholipase
      C.
AB  - The signalling pathways by which muscarine and epidermal growth factor (EGF)
      regulate the secretion of the alpha-secretase cleavage product (sAPPalpha) of the
      amyloid precursor protein (APP) were examined in the human neuroblastoma SH-SY5Y.
      Using specific inhibitors it was found that over 80% of sAPPalpha secretion,
      enhanced by muscarine, occurred via the extracellular signal-regulated kinase
      (ERK1/2) member of the mitogen-activated protein kinase (MAPK) family and was
      dependent on protein kinase Calpha (PKCalpha) and a member of the Src family of
      non-receptor tyrosine kinases (Src-TK). In contrast the stimulation of sAPPalpha
      secretion by EGF was not affected by inhibitors of PKC nor Src-TK but was
      dependent on ERK1/2. In addition muscarine-enhanced sAPPalpha secretion and
      ERK1/2 activation were inhibited 60 and 80%, respectively, by micromolar
      concentrations of the phosphatidylinositol 3 kinase (PI-3K) inhibitor wortmannin.
      In comparison wortmannin decreased EGF stimulation of sAPPalpha secretion and ERK
      1/2 activation by approximately 40%. Unexpectedly, U73122, an inhibitor of
      phosphoinositide-specific phospholipase C, did not inhibit muscarine enhancement
      of sAPPalpha secretion. These data are discussed in relation to a pathway for the
      enhancement of sAPPalpha secretion by muscarine which involves the activation of
      a Src-TK by G-protein beta/gamma-subunits leading to activation of PKCalpha, and
      ERK1/2 by a mechanism not involving phospholipase C.

PMID- 12191496
TI  - PKC, p42/44 MAPK and p38 MAPK regulate hepatocyte growth factor secretion from
      human astrocytoma cells.
AB  - Hepatocyte growth factor (HGF) and its receptor c-Met are expressed in
      inappropriately high abundance in gliomas and are further upregulated during the
      transition from low- to high-grade malignancy. In these cells HGF induces
      expression of c-Met via PKC, Ras and mitogen activated protein kinase (MAPK)
      pathway. Here we report that secretion and expression of HGF in U87 astrocytoma
      is increased by a PKC activator, PMA, an effect which is abolished by a PKC
      inhibitor, Go6976, specific for PKCalpha and PKCbeta1. Activating PKA by
      forskolin, on the other hand, had no effect. Furthermore, messenger molecule
      downstream of PKC, i.e. MEK mediates such effect of PKC as specific MEK
      inhibitors (PD98059 and U0126) abolished PMA induced HGF secretion by U87 cells.
      Accordingly, PMA induced rapid phosphorylation of MEK substrate, i.e. Erk1/2
      (p42/44 MAPK). In addition, such effect of PKC is Ras-dependent as specific Ras
      inhibitor L-744,832 attenuated both PMA mediated induction of Erk 1/2
      phosphorylation as well as HGF secretion. Moreover, a specific p38 MAPK inhibitor
      (SB203580) almost completely inhibited basal HGF secretion to an undetectable
      level. Increased secretion of HGF is most likely exerted at the transcriptional
      level since inhibitor of transcription, actinomycin D abolished such increase.
      Furthermore, when assessed by Northern blot analysis, PMA increased HGF
      transcripts while U0127 and SB203580 inhibited. Therefore, our data reveal that
      HGF secretion in U87 cells is regulated by Ras-dependent PKC, MEK cascade and in
      parallel by p38 MAPK pathway. Since the Raf-PKC-MEK cascade is used for HGF's
      signaling via its receptor in astrocytoma cells, our data revealing similar
      regulatory mechanism for HGF secretion in these cells would help to explain the
      feed forward nature of HGF action in glioma cells that would further accentuate
      its basal secretion, exacerbating its effects on the progression of gliomas in an
      autocrine fashion.

PMID- 12191497
TI  - In vivo and in vitro localization of brain-derived neurotrophic factor,
      fibroblast growth factor-2 and their receptors in the bullfrog vestibular end
      organs.
AB  - The inner ear sensory epithelia of vertebrates are composed mainly of supporting
      cells and hair cells (HCs). Brain-derived neurotrophic factor (BDNF) and
      fibroblast growth factor-2 (FGF-2) are trophins that are believed to play an
      essential role in the development and innervation of inner ear epithelia. Both
      trophins also may play a crucial role in the maintenance and regeneration of hair
      cells in the adult vertebrate ear. In the bullfrog vestibular system, hair cells
      are produced throughout life, and the epithelia regenerates following
      ototoxicity. The expression of BDNF and FGF-2 in the vestibular organs of the
      adult bullfrog was investigated at a cellular level both in histological sections
      and in vitro in dissociated cell cultures. In histological sections of the crista
      ampullaris, in situ hybridization and immunocytochemical techniques demonstrated
      that HCs express both BDNF and its receptor trkB, while the supporting cells
      express the receptor trkB alone. Following dissociation and in vitro cell culture
      no changes in the pattern of BDNF and trkB receptor were observed.
      Immunocytochemical studies demonstrated that in vivo hair cells express FGF-2 and
      the receptors FGFR-1 and FGFR-2 while supporting cells do not express either
      molecule. Following dissociation, HCs continue to express FGF-2 and its two
      receptors, while supporting cells upregulate the expression of FGF-2 and its
      receptor FGFR-2. These data confirm the potential role of BDNF and FGF-2 trophic
      regulation of the sensory epithelia of the adult inner ear. The findings suggest
      that BDNF has a role in the maintenance of the vestibular epithelia while FGF-2
      may regulate the proliferation of supporting cells.

PMID- 12191498
TI  - Developmental expression and enzymatic activity of pre-mRNA deaminase in
      Drosophila melanogaster.
AB  - Pre-mRNA editing, conducted by adenosine deaminase acting on RNA (ADAR), plays an
      important role in many biological/physiological processes. This post
      transcriptional event creates protein diversity that stems from a single gene via
      alteration of either genetic codons or alternative splicing sites. Our data
      demonstrate that both expression of Drosophila ADAR (dADAR) gene and dADAR
      editing activity are highly regulated during development. The lack of editing
      activity during embryonic development and the CNS-limited expression of dADAR in
      the adult may specify its important role in maintaining neuronal function in the
      Drosophila CNS.

PMID- 12191499
TI  - Increased expression of mRNAs for microtubule disassembly molecules during nerve
      regeneration.
AB  - The mRNA expression of the microtubule disassembly molecules (SCG10, stathmin,
      SCLIP and RB3) in response to nerve injury was examined using a rat hypoglossal
      nerve injury model. After nerve injury prominent increase in mRNA expression of
      SCG10, stathmin and RB3 was observed, while only slight increase in SCLIP mRNA
      was observed in injured motor neurons. The increase in SCG10 and RB3 mRNA
      expression was quicker than that of stathmin and SCLIP. All the elevated signals
      decreased gradually to control levels by 4 weeks after nerve injury.

PMID- 12191501
TI  - Mutation of NMDA receptor subunit epsilon 1: effects on audiogenic-like seizures
      induced by electrical stimulation of the inferior colliculus in mice.
AB  - It has been shown that the N-methyl-D-asparate (NMDA) receptor in the inferior
      colliculus is involved in the induction of audiogenic seizures (AGS). In the
      present study we examined audiogenic-like seizure susceptibility in GluR epsilon
      1 null KO adult mice (n=32) and wild-type adult mice (n=28) by electrically
      stimulating the inferior colliculus (IC). Threshold current intensities of the
      GluR epsilon 1 KO mice for wild running, clonic and tonic seizures were higher
      than those of wild-type mice. In addition, the incidence rates of each seizure
      syndrome in GluR epsilon 1 KO mice were lower than in wild-type mice at each
      current intensity. These results show that GluR epsilon 1 KO mice were more
      resistant to audiogenic-like seizures induced by stimulating the IC. Thus, our
      findings suggest that the GluR epsilon 1 subunit plays an important role in
      regulating AGS.

PMID- 12191500
TI  - Tool-use learning induces BDNF expression in a selective portion of monkey
      anterior parietal cortex.
AB  - Learning but not execution of tool-use induced expression of brain-derived
      neurotrophic factor (BDNF). The expression was highest in the anterior bank of
      the intraparietal sulcus, especially in the region posteriorly adjacent to the
      somatosensory shoulder and forearm region in area 3b, suggesting that BDNF plays
      a role in altering the body image of the hand to include the repeatedly used tool
      as its extension.

PMID- 12191502
TI  - Differential D1 and D2 receptor-mediated effects on immediate early gene
      induction in a transgenic mouse model of Huntington's disease.
AB  - The diminished expression of D1 and D2 dopamine receptors is a well-documented
      hallmark of Huntington's disease (HD), but relatively little is known about how
      these changes in receptor populations affect the dopaminergic responses of
      striatal neurons. Using transgenic mice expressing an N-terminal portion of
      mutant huntingtin (R6/2 mice), we have examined immediate early gene (IEG)
      expression as an index of dopaminergic signal transduction. c-fos, jun B, zif268,
      and N10 mRNA levels and expression patterns were analyzed using quantitative in
      situ hybridization histochemistry following intraperitoneal administration of
      selective D1 and D2 family pharmacological agents (SKF-82958 and eticlopride).
      Basal IEG levels were generally lower in the dorsal subregion of R6/2 striata
      relative to wild-type control striata at 10-11 weeks of age, a finding in accord
      with previously reported decreases in D1 and adenosine A2A receptors. D2
      antagonist-stimulated IEG expression was significantly reduced in the striata of
      transgenic animals. In contrast, D1-agonist-induced striatal R6/2 IEG mRNA levels
      were either equivalent or significantly enhanced relative to control levels, an
      unexpected result given the reduced level of D1 receptors in R6/2 animals.
      Understanding the functional bases for these effects may further elucidate the
      complex pathophysiology of Huntington's disease.

PMID- 12191503
TI  - A comparative investigation of CC chemokines and SIV suppressor factors generated
      by CD8+ and CD4+ T cells and CD14+ monocytes.
AB  - The capacity of CD8+ and CD4+ T cells and CD14+ monocytes to generate the CC
      chemokines, RANTES, MIP-1alpha and MIP-1beta, and SIV suppressor factors were
      studied using cells separated from PBMC of macaques immunized with the 70-kDa
      heat shock protein (HSP70). Unimmunized macaques showed low levels of the three
      CC chemokines and SIV-SF, and they showed little variation between PBMC and the
      two subsets of T cells stimulated with PHA. Immunization with HSP70 elicited an
      increase in the in vitro concentration of each of the three CC chemokines and SF.
      This was found with PBMC, CD4+ and CD8+ T cells and to a lesser extent with
      monocytes, when conventionally separated enriched cell subsets were examined from
      the same PBMC. However, the concentrations of the three CC chemokines derived
      from highly purified cell-sorted populations (>95%) were greatly increased, as
      compared with the enriched cell subsets. The concentration of each of the three
      chemokines was highest for CD8+ T cells, decreased with CD4+ T cells and was
      lowest with the CD14+ monocytes, but the latter were not stimulated.
      Neutralization assays with antibodies to the three CC chemokines showed that the
      antiviral activity generated by the four populations of cells could be largely
      accounted for by the three CC chemokines. The results of this comparative study
      suggests that CD8+ as well as CD4+ T cells and CD14+ monocytes generate the three
      CC chemokines and SIV-SF when stimulated with a mitogen, and that the baseline
      innate level can be upregulated by adaptive immune responses to a specific
      antigen.

PMID- 12191504
TI  - Area under the curve calculations as a tool to compare the efficacy of equine
      influenza vaccines--a retrospective analysis of three independent field trials.
AB  - Using the area under the curve (AUC) concept as is commonly used in
      pharmaceutical bioequivalence studies, the bioequivalence of three equine
      influenza vaccines was demonstrated. A retrospective analysis was performed using
      this technique on data generated in three trials in which each of the three
      vaccines had been used. In total, data from 63 pony and horse foals were used.
      The AUC of the single radial hemolysis (SRH) titres against Influenza A/equi
      1/Prague/56 (Pr/56), A/equi-2/Newmarket-1/93, and A/equi-2/Suffolk/89 (Suf/89)
      were calculated for each horse. It was concluded that calculation of the AUC from
      four time-points permitted a suitable estimate for vaccine potency. Using pooled
      data, it appeared that the AUC permitted better evaluation of vaccine potency
      than simply considering the highest post vaccinal titre (Titremax). In two
      studies, a minimal value for the AUC was associated with protection against
      Influenza (H3N8) challenge 50-153 days later.

PMID- 12191505
TI  - Cell surface phenotyping and cytokine production of Epstein-Barr Virus (EBV)
      transformed lymphoblastoid cell lines (LCLs).
AB  - Epstein-Barr Virus-transformed B lymphoblastoid cell lines (EBV-LCLs) are
      routinely used for the in vitro expansion of T cells. However, these cell lines
      are reported to produce the cytokine IL-10, which is inhibitory for T cells. We,
      therefore, characterized a panel of 37 EBV-LCLs for a variety of cell surface
      markers, for secretion of various cytokines including IL-10 and for
      immunoglobulin production. These cell lines were derived from normal donors or
      patients with nonsmall cell lung cancer, acute myelogenous leukemia, melanoma or
      colon cancer. Overall, 26 lines were positive for CD19 and CD20, and 11 were
      negative for both. All of the lines were strongly HLA-DR+, while CD40 expression
      was variable. Twenty-four (65%) were both CD23+ and secreted immunoglobulin, and
      33 expressed kappa and/or lambda light chains. Additionally, all of the EBV-LCLs
      were negative for T cell (CD3), NK cell (CD16, CD56), monocyte (CD14) and
      granulocyte (CD66b) surface markers. Some level of IL-10, IL-6, IL-12p40 and TNF
      alpha cytokine production was detected in 33, 18, 19 and 12 EBV-LCLs,
      respectively. Together, these data reflect the heterogeneity of EBV-LCLs, which
      cautions their use nondiscriminately in various immunologic assays.

PMID- 12191506
TI  - Three-step purification of gp96 from human liver tumor tissues suitable for
      isolation of gp96-bound peptides.
AB  - Glycoprotein 96 (gp96), a member of heat shock protein (HSP) family, plays
      important roles in both innate immunity by itself and in T cell adaptive immunity
      in complex with antigenic-specific peptides. Using ammonium sulfate
      precipitation, ConA-Sepharose affinity chromatography and anion exchange
      chromatography, we have successfully purified gp96 from human liver tumor
      tissues. Subsequently, the gp96-associated peptides were successfully isolated
      from the gp96 preparation in quantities sufficient for micro-sequencing and
      identification of the peptides [Lancet 357 (2001) 528]. This three-step
      purification method might be used as a universal technique for the easy and
      reproducible isolation of antigenic heat shock protein gp96 from liver tissue or
      even other tissues of different sources. This will inevitably trigger the search
      for antigenic-specific peptides bound to gp96. Here, we report the method in
      detail.

PMID- 12191507
TI  - Removal of detergents from protein extracts using activated charcoal prior to
      immunological analysis.
AB  - The use of dextran-coated activated charcoal (DCC) powder to absorb solubilising
      detergents from cell lysates is described. Normal embryonic epithelial cells were
      lysed in the presence of sodium dodecyl sulphate (SDS). The detergent was then
      absorbed with DCC to facilitate analysis of polycystin-1 with antibody-based
      methods. Polycystin-1 is a membrane protein that is involved in the pathogenesis
      of autosomal dominant polycystic kidney disease (ADPKD). The adverse effect of
      SDS on antibody-polycystin-1 binding was studied and the improvement resulting
      from its removal demonstrated using enzyme-linked immunosorbent assays (ELISAs).
      The results indicate that DCC can be used in a simple manner to remove highly
      reactive membrane-solubilising reagents from protein mixtures prior to
      immunological analysis. This procedure may be relevant to a variety of other
      techniques that are normally affected by detergents.

PMID- 12191508
TI  - The production and characterisation of dinitrocarbanilide antibodies raised using
      antigen mimics.
AB  - Polyclonal antibodies were produced to detect the coccidiostat nicarbazin. Due to
      structural constraints of the active component of nicarbazin, dinitrocarbanilide
      (DNC), three different compounds that shared a common substructure with DNC were
      used as antigen mimics. The compounds (N-succinyl-L-alanyl-L-alanyl-L-alanine 4
      nitroanilide (SAN), L-glutamic acid gamma-(p-nitroanilide) (GAN) and p
      nitrosuccinanilic acid (NSA)) were conjugated to a carrier protein and used in
      the immunisation of rabbits. Five different polyclonal sera were produced and
      consequently characterised. The antibodies exhibited an IC(50) range of 2.3-7.6
      ng/ml using a competitive ELISA procedure. Serum from one rabbit, R555, exhibited
      an IC(50) of 2.9 ng/ml for DNC and cross-reactivity studies showed that this
      serum was specific for DNC and did not cross-react with other coccidiostats such
      as halofuginone, toltrazuril or ronidazole.

PMID- 12191509
TI  - Chemically synthesized solid phase oligosaccharide probes for carbohydrate
      binding receptors. Interactions of the E-, L- and P-selectins with sialyl-Le(x)
      and O-sulphated forms linked to biotin or to polyacrylamide.
AB  - There is a growing interest in chemically defined oligosaccharide reagents for
      identifying proteins that bind carbohydrates and determining the specificities of
      carbohydrate-binding proteins. Here, we compare three sets of chemically
      synthesized commercially available oligosaccharide conjugates as immobilized
      probes, for the binding signals that they elicit with known carbohydrate-binding
      receptors of the immune system, the E-, P- and L-selectins. The first set of
      conjugates is of oligosaccharides linked to biotin via a nine-carbon spacer. The
      second and third sets are multivalent derivatives in which the oligosaccharides
      are linked, via a three-carbon spacer to poly[N-(2-hydroxyethyl)acrylamide] (PAA)
      or to biotinylated PAA with an average of 20% substitution of the hydroxyethyl
      amide groups by carbohydrate. The conjugates were immobilized on streptavidin
      coated microwells if biotinylated, otherwise by drying in uncoated wells. The
      most robust binding curves, overall, were with the biotinylated PAA derivatives
      of the ligands immobilized on streptavidin wells. These reagents have permitted a
      reevaluation of selectin binding signals elicited by sialyl-Lewis(x) (SLe(x))
      analogues having sulphate at position 6 of the galactose (6'SuSLe(x)) or of the N
      acetylglucosamine (6SuSLe(x)). The results clarify the role of 6SuSLe(x), rather
      then 6'SuSLe(x), as a ligand for the selectins.

PMID- 12191510
TI  - Dialysis-based bioreactor systems for the production of monoclonal antibodies-
      alternatives to ascites production in mice.
AB  - Two commercially available bioreactor systems, CELLine and miniPERM, were
      evaluated for their ability to support the production of monoclonal antibody
      (mAb) from a variety of murine hybridoma cell lines. Production and purity of
      mAbs were compared between the two systems and with mouse ascites tumour fluid
      generation. The quality and purity of the mAb generated by each method was
      analysed on SDS-PAGE gels and the antibody immunoreactivity in each case was
      quantified by indirect ELISA tests. The relative benefits of conventional growth
      medium (Dulbecco's modified Eagle's media, DMEM) and serum-free medium (hybridoma
      serum-free media, H-SFM) using the miniPERM system were also analysed, in terms
      of the amount of antibody produced, cell concentration and specific antibody
      titre. In all cases, the CELLine units tested gave higher protein concentrations
      compared to the miniPERM system under the same conditions (means and 95%
      confidence limits are 4.2+/-0.8 and 2.1+/-0.8 mg/ml, respectively), yet the
      miniPERM system yielded greater total amounts over a similar culture period
      (428.7+/-243.3 mg compared to 183.3+/-100.9 mg in the CL-350 CELLine unit). When
      defined by specific ELISA titre, both bioreactor systems yielded mAb levels that
      compared favourably with those derived from ascites. In addition, SDS-PAGE
      analysis indicated that the bioreactor antibody product was relatively free of
      contaminating protein, whereas ascites tumour fluid preparations displayed
      significant levels of extraneous protein. This study has shown that both
      bioreactor systems are acceptable in vitro alternatives to the in vivo production
      of mAbs in mice.

PMID- 12191511
TI  - Development of a novel allo-independent HIV-1 virus preparation for use in
      immunoassays.
AB  - The study of the immunologic response to whole human immunodeficiency virus type
      1 (HIV-1) antigen is limited by the presence of highly immunogenic human
      leukocyte antigen (HLA) alloantigens on the envelope of wild type virus. This
      paper outlines the production of HIV-1 infectious virions free of HLA for use as
      whole viral antigens in immunoassays. An infectious molecular clone of HIV-1 was
      transfected into the K-562 cell line, which does not express HLA on the cell
      surface. After a 30-day selection period, to ensure stable transfection, cells
      and culture supernatants were analyzed for productive HIV-1 infection and virion
      infectivity. An enzyme-linked immunosorbent assay (ELISA) confirmed the presence
      of p24 in the culture supernatants. Molecular confirmation of HIV-1 transfection
      was achieved by gene amplification. Flow cytometric analysis was used to identify
      gp120 on the surface of the infected cells. Viral supernatants were tested for
      HIV infectivity in peripheral blood mononuclear cells (PBMCs). The usefulness of
      this viral preparation as whole virus antigens was validated using PBMCs from HIV
      infected individuals. These results indicate the successful production of HIV-1
      infectious virions, which do not have HLA molecules on their viral envelope, and
      demonstrate their utility for immunoassays.

PMID- 12191512
TI  - A new method for detecting TNF-alpha-secreting cells using direct
      immunofluorescence surface membrane stainings.
AB  - In the present study, a new flow cytometric method for the identification of TNF
      alpha-secreting cells based on the use of a TNF-alpha converting enzyme (TACE)
      inhibitor compound (BB3103) is described. TNF-alpha secreting cells were measured
      in parallel in stimulated peripheral blood samples (n=4), using the BB3103 TACE
      inhibitor or brefeldin A as secretion blocking agents. To induce TNF-alpha
      production by PB T-cells and monocytes, whole blood samples were stimulated
      either for 4 h with PMA plus ionomycin or for 6 h with LPS plus IFNgamma,
      respectively. Interestingly, slightly higher percentages of TNF-alpha(+) CD4(+)
      (65+/-11% versus 49+/-11.4%, p=0.06) and TNF-alpha(+) CD8(+) (60+/-9.9% versus
      47+/-27.7% p=0.46) T-cells together with a greater amounts of TNF-alpha/cell-mean
      fluorescence intensity (MFI) of 1050+/-230 versus 258+/-112 for CD4(+), p=0.06
      and 424+/-169 versus 266+/-201 for CD8(+), p=0.27-were found for activated T
      lymphocytes cultured with BB3103 as compared to those treated with brefeldin A.
      Kinetic analysis of surface TNF-alpha expression under these stimulatory
      conditions showed detectable surface TNF-alpha levels on both T-cells and
      monocytes after 30 min. Thereafter, surface TNF-alpha expression on both T-cells
      and monocytes progressively increased for up to 3 and 4 h, respectively. From
      this time on, a decrease in the membrane levels of TNF-alpha was observed in the
      monocytes, presumably due to the occurrence of cell death. In order to show that
      the BB3103 inhibitor was also active on other TACE-associated molecules, CD62L
      expression on PMA-stimulated PB lymphocytes, monocytes and neutrophils was
      analyzed by flow cytometry in the presence and absence of BB3103. The TACE
      inhibitor proved to be active in stabilizing CD62L expression on PMA-stimulated
      PB leukocytes. In summary, our results show that stimulation of PB T-cells and
      monocytes in the presence of the TACE inhibitor BB3103 followed by surface
      staining for TNF-alpha provides a new, simple and rapid method for the
      identification of intact TNF-alpha producting cells present in a sample without
      the need for prior cell fixation and permeabilization. In addition, this approach
      could also be applied in order to stabilize the expression of other
      metalloprotease-sensitive molecules such as CD62L on the surface of PB
      leukocytes.

PMID- 12191513
TI  - Introduction of a novel proliferation assay for pharmacological studies allowing
      the combination of BrdU detection and phenotyping.
AB  - A recently developed technology for the non-enzymatic detection of the thymidine
      analog 5-bromo-2-deoxyuridine (BrdU) has been evaluated. In contrast to previous
      enzymatic approaches, Ultraviolet-Induced Detection (UVID) of halogenated
      pyrimidines allows for a mild detection procedure which enables the simultaneous
      detection of cellular markers and DNA-synthesis without enzyme-specific
      disadvantages. Superantigen-stimulated peripheral blood mononuclear cells
      (PBMNCs) have been treated with two different inhibitors of proliferation and the
      cell cycle of different lymphocyte subsets has been analysed. Both pentoxifylline
      (POF) and 2-methoxyestradiol (2ME2) exhibited strong antiproliferative activity,
      but led to distinctive changes in the cell cycle distribution. This study shows
      that the UVID technology is a simple and viable method which should find a wide
      range of applications in immunological and pharmacodynamic assays.

PMID- 12191514
TI  - Cytokine profiles using whole-blood assays can discriminate between tuberculosis
      patients and healthy endemic controls in a BCG-vaccinated population.
AB  - Whole-blood assays (WB) provide a simple tool for assessing immune cytokine
      profiles which may be useful laboratory predictors of early disease, aiding the
      evaluation of new tuberculosis (TB) vaccines and offering insights into disease
      pathogenesis. Although BCG does not provide protection against pulmonary disease
      in TB endemic areas, it does modulate immune responses to mycobacterial antigens.
      It is important, therefore, to evaluate any new tool in an endemic setting in
      both BCG vaccinees and patients with tuberculosis. We have assessed the optimal
      conditions in terms of dose and kinetics of those cytokines which are released
      early (TNF-alpha, IL6 and TGF-beta, IL10) or (interferon [IFN]-gamma and IL5) in
      WB cultures stimulated with mitogens and mycobacterial antigens. Responses were
      studied in parallel in untreated TB patients and endemic control groups. Optimal
      responses to LPS (predominantly monocyte-derived) occurred on days 1-2, whereas
      for PHA (predominantly T-cell-derived), they were on days 3-5. Secreted
      Mycobacterium tuberculosis culture filtrate proteins (CFP) provided a stronger
      stimulus for monocyte-derived cytokines compared to PPD, but both antigens were
      comparable for induction of T-cell cytokines. Using unpaired Student's t-tests,
      pulmonary tuberculosis patients (P.TB; n=11), in response to CFP, showed higher
      monocyte-derived IL6 (p=0.023) and IL10 (p=0.042) compared to endemic controls
      (EC; n=13), and significantly suppressed T-cell-derived IFN-gamma (p=0.028) and
      IL5 (p=0.012) secretion but increased IL10 (p=0.047) on day 5, indicating that
      CFP is a strong stimulus for IL10 secretion in pulmonary TB patients.
      Extrapulmonary TB patients (E.TB; n=6) showed no elevation of early monocyte
      derived cytokines to either PPD or CFP, but showed a marked suppression of the T
      cell-derived cytokines IFN-gamma (PPD, p=0.015; CFP, p=0.05) and IL5 (PPD,
      p=0.05; CFP, p=0.015). Cytokine analysis in WB cultures is, therefore, able to
      discriminate between active tuberculosis infection and nondiseased healthy
      controls.

PMID- 12191515
TI  - Differential expression of inhibitory and activating CD94/NKG2 receptors on NK
      cell clones.
AB  - Natural killer cells are known to express a variety of surface receptors involved
      in HLA class I monitoring. It is thus of interest to investigate the clonal
      distribution and relative expression levels of activating versus inhibitory NK
      receptors. We have developed a quantitative real-time reverse transcription
      polymerase chain reaction (RT-PCR) assay designed to determine specific and
      absolute mRNA levels for NKG2-A/B, -C, -E, -F, -H and NKG2-D. When analyzing NK
      cell clones derived from a single donor we found differential expression of
      inhibitory (NKG2-A/B) versus triggering (NKG2-C and potentially -E, -F, -H) NK
      receptor chains. The generation of the splice variants NKG2-E and -H seemed to
      occur at a constant ratio. We further compared NKG2 transcript levels to surface
      receptor expression as monitored by flow cytometric analysis and to NK cell
      cytotoxicity as detected by reverse ADCC: a clear correlation was observed. Thus,
      the data obtained reveal a substantial variability in the NKG2 repertoire among
      NK cell subpopulations, which is likely to affect the sensitivity and reactivity
      towards the ligand HLA-E.

PMID- 12191516
TI  - Immunization procedures for anti-idiotypic antibody induction in mice and rats.
AB  - Anti-idiotypic antibodies (Ab2) mimicking antigens (Ags)-defined by antibodies
      (Ab1) directed to tumors or pathogens have elicited Ag-specific humoral, cellular
      and/or protective immunity in experimental animals and in humans. In
      immunizations of rodents with Ab1, factors such as animal species, form of Ab1
      and choice of adjuvant are crucial for the successful induction of Ab2 as
      candidate vaccines against tumors and pathogens. Here we survey the outcome of
      362 fusion events (each event representing one animal), using nine immunization
      schedules in mice and seven schedules in rats and including 10 different Ab1
      directed against human tumor- and immunodeficiency virus (HIV-1)-associated Ags.
      Ab1 IgG or F(ab')2 were administered uncoupled or coupled to keyhole limpet
      hemocyanin (KLH). As adjuvants, complete and incomplete Freund's adjuvant
      (CFA/IFA), lipid A, aluminum hydroxide, TiterMax or vaccinia virus were used. In
      syngeneic immunizations with murine Ab1 in mice, F(ab')2 coupled to KLH and
      emulsified in CFA/IFA preferentially induced Ab2 mimicking tumor or HIV-1
      associated epitopes. In xenogeneic immunizations with mouse Ab1 in rats, various
      forms of Ab1 and adjuvants successfully induced Ab2 mimicking tumor Ags.

PMID- 12191517
TI  - Generation of large numbers of dendritic cells in a closed system using Cell
      Factories.
AB  - There is a growing interest in using dendritic cells (DC) for vaccine approaches
      in the treatment of cancer and infectious diseases. This requires a reproducible
      method for the generation of large numbers of DC in a closed culture system
      suitable for clinical use and conforming to the current guidelines of good
      manufacturing practices. We designed a system in which the DC were generated in a
      closed system from adherent monocytes using Cell Factories (DC-CF). Monocytes
      were enriched from apheresis products by adherence and then cultured in the
      presence of AB serum or autologous plasma and GM-CSF and IL-4 for 6 days. The DC
      generated in Cell Factories were extensively compared to research-grade DC
      generated in conventional tissue culture flasks (DC-TCF). At day 6, the immature
      DC were harvested and the yield, the viability, the immunophenotype and the
      functional characteristics of the DC were compared.DC-CF and DC-TCF showed
      similar viability and purity and scored equally when tested for stability,
      dextran and latex bead uptake, in MLR and in the activation of influenza-specific
      memory cells after electroporation with influenza matrix protein 1 (IMP1) mRNA.
      These data indicated that large numbers of functional clinical-grade DC could be
      generated from adherent cells in a closed system using Cell Factories.

PMID- 12191519
TI  - An immuno-precipitation assay for determining specific interactions between
      antibodies and phage selected from random peptide expression libraries.
AB  - Libraries of random peptides displayed by bacteriophage can be screened to select
      phage expressing peptides that specifically bind antibodies, so that the peptide
      sequence motifs expressed by the phage can help to define the epitopes of the
      antibodies. It is often desirable to screen antibody-selected phage for binding
      of the selecting antibody in an immunoassay in order to verify the specificity of
      the interaction. Enzyme-linked immunosorbent assays (ELISAs) are commonly used
      for this purpose. However, for many antibodies, the best techniques for measuring
      specific, high affinity interactions are immuno-precipitation assays. Immuno
      precipitation was therefore investigated as a means of measuring interactions
      between antibodies and phage clones selected from random peptide display
      libraries. Three mouse monoclonal antibodies specific for glutamic acid
      decarboxylase were used to select peptides as 9-mers on T7 phage, linear 12-mers
      on pIII of M13 phage, or constrained 15-mers on pVIII of M13 phage. Following the
      cloning and sequencing of selected phage, mixtures of antibody and phage were
      incubated in solution and the immune complexes were precipitated with Protein G
      bound to Sepharose beads. In order to detect and quantitate the phage that had
      formed immune complexes and been precipitated, advantage was taken of the
      biological properties of the phage by inducing infection of Escherichia coli by
      the precipitated phage. The aim was to quantitate the phage precipitated by
      determining the number of plaques produced, which would therefore be proportional
      to the degree of interaction between the phage and the antibody in solution. The
      results presented here indicate that this method of measuring monoclonal antibody
      interactions with phage selected for expression of peptides recognised by the
      monoclonal antibody is highly specific and sensitive.

PMID- 12191518
TI  - Freezing and thawing of bone marrow-derived murine dendritic cells with
      subsequent retention of immunophenotype and of antigen processing and
      presentation characteristics.
AB  - Murine dendritic cells (DCs) are widely used for experimental vaccinations in
      mouse models. A high-yield method for freezing and thawing batches of these
      cells, if compatible with retention of cell immunophenotype, would reduce the
      time required for repeated preparations from DC precursors in bone marrow (BM),
      as well as variability among lots. Following depletion of specific lineages,
      murine bone marrow cells from C57BL/6 inbred-strain mice were grown in medium
      containing 10% fetal calf serum (FCS) and granulocyte/macrophage colony
      stimulating factor (GM-CSF); after 6 days, large numbers of immature DCs were
      obtained. The immature cells were frozen in complete medium with GM-CSF and 10%
      DMSO, at a cell density of 5x10(6) DCs/ml. After thawing, 80% of DCs survived;
      they were induced to mature by addition of lipopolysaccharide (LPS). In
      comparison with fresh DCs, the thawed DCs had similar morphology, purity, and
      expression of class I (H-2D(b) and H-2K(b)) and class II major histocompatibility
      complex (MHC) proteins, as well as CD11b, CD11c, CD40, CD80, and CD86 molecules.
      Freeze-thawing did not affect trafficking to T cell areas of spleen, nor reduce
      the capacity to stimulate an alloresponse. Frozen-thawed cells were also
      proficient at uptake, processing, and presentation of native or denatured
      ovalbumin (OVA) protein to a peptide-specific T cell hybridoma, and were able to
      induce T cell responses in vivo after being loaded with denatured OVA protein.
      The ability to freeze and thaw DCs, and to obtain high yields without altering
      their essential properties, will facilitate future immunotherapy experiments in
      laboratory mouse models.

PMID- 12191520
TI  - Scavenger receptor block as strategy for the identification of bone marrow homing
      phages by panning in vivo random peptide phage displayed libraries.
AB  - Surface molecules exclusively expressed by cells of the bone marrow (BM) are
      candidate targets for delivering therapeutic agents to this tissue. To identify
      ligands specific for the BM, we performed a series of pannings in vivo with
      random peptide phage displayed libraries (RPPDL). We could show that phages bind
      to bone marrow endothelium (BME) independently of the peptide insert, suggesting
      that the BM, similarly to spleen and liver, is part of the reticulo-endothelial
      system (RES). Furthermore, this strong "natural" affinity to the BME was
      abrogated by polyanions, indicating that phage trapping by this endothelium is
      mediated by scavenger receptors (SR). To circumvent interference by SR,
      polyinosinic acid was administered before phage panning in vivo. This led to the
      identification of a consensus motif that confers binding specificity for a
      subpopulation of hemopoietic marrow cells. Thus, SR inhibition, by avoiding phage
      trapping by the endothelium, seems to allow phage particles to extravasate and
      reach parenchymal cells. Accordingly, this panning strategy in vivo may be useful
      for the identification of targeting motifs specific for cells located in the
      extravascular space of various tissues.

PMID- 12191521
TI  - Isolation of monoclonal antibodies recognizing rare and dominant epitopes in
      plant vascular cell walls by phage display subtraction.
AB  - A combination of phage display antibody technology and a subtraction method
      provides a powerful tool for the isolation of novel biomarkers. However, the
      dilemma that high stringency screening often reduces the diversity in the
      subtracted phage antibody repertoires and that it is difficult to isolate phage
      antibody against rare epitopes remain. Therefore, we carefully monitored the
      occupancy of differentiation-specific clones in a phage antibody library through
      an enrichment process, and succeeded in isolating monoclonal antibodies against
      rare and dominant epitopes in plant vascular cell walls. We also report that
      clones with stop and frameshift mutations significantly survived the enrichment
      process, owing to noncanonical translation mechanisms.

PMID- 12191522
TI  - Expression of recombinant proteinase 3, the autoantigen in Wegener's
      granulomatosis, in insect cells.
AB  - Proteinase 3 (PR3) is the major autoantigen for anti-neutrophil cytoplasmic
      antibodies (ANCA) in patients with Wegener's granulomatosis. Little is known
      about the major antigenic sites on PR3. To facilitate epitope mapping, PR3 was
      cloned in insect cells using a baculovirus expression system. Four different
      sequences of the PR3 cDNA were amplified by PCR: two clones containing the pro
      peptide of PR3 with or without a His-tag (rproPR3-his and rproPR3, respectively)
      and two clones without the pro-peptide and with or without a His-tag (rPR3-his
      and rPR3, respectively). The PR3 sequences were cloned behind the polyhedrin
      promoter and the honeybee melittin signal peptide enabling secretion of rPR3.
      Plasmids were transposed into the genome of baculovirus, and wild types as well
      as PR3-containing virus genomes were transfected into Sf21 insect cells. All four
      rPR3 variants were secreted into the medium and were recognized by anti
      neutrophil PR3 rabbit serum and by at least two anti-PR3 monoclonal antibodies.
      Mature forms of PR3 were recognized by almost all patient sera, whereas the pro
      forms of PR3 were recognized by 14 of 18 PR3-ANCA sera tested. On SDS-PAGE, the
      four rPR3 forms migrated at approximately 32 kDa. RPR3-his and rproPR3-his could
      be purified by means of this His-tag. In conclusion, especially the mature rPR3s
      are well recognized by PR3-ANCA sera. The presence of a C-terminal His-tag
      facilitated purification of His-tagged rPR3. Thus, rPR3 expressed in insect cells
      can be used as a tool for diagnostic tests as well as for epitope mapping
      studies.

PMID- 12191523
TI  - Optimised SEREX technique for the identification of leukaemia-associated
      antigens.
AB  - The serological analysis of antigens by recombinant expression cloning (SEREX)
      has been used by many laboratories to immunoscreen lambda phage cDNA libraries
      produced from a range of tumour cell types. We and others have found it difficult
      to extract an optimal quality and quantity of mRNA for the preparation of cDNA
      libraries which represent the genes transcribed in haematological samples. The
      difficulty is believed to be due to residual haem groups in the isolated RNA
      sample which inhibit the activity of reverse transcriptase used in the later
      production of cDNA. During our preparation of a cDNA library for SEREX studies,
      we optimised the isolation of mRNA from samples from patients with haematological
      malignancies. We compared the efficacy of different methods of mRNA extraction
      using a range of haematological sample sizes and describe the most efficient
      techniques to maximise mRNA yield and quality for cDNA library production. The
      phage library we prepared contained a range of cDNA insert sizes, including high
      molecular weight sequences which, following immunoscreening with autologous
      patient sera, led to the isolation of 17 novel antigens. Using the methodology
      described, we have shown SEREX to be effective for the isolation of leukaemia
      associated antigens, which may act as targets for immunotherapy.

PMID- 12191525
TI  - The association of nuchal cord with cerebral palsy is influenced by recording
      bias.
AB  - OBJECTIVES: To determine if the association of cerebral palsy (CP) with umbilical
      cord around the fetal neck (nuchal cord) is the result of recording bias. STUDY
      DESIGN: Population-based case control study. RESULTS: There were 68 cases with
      cerebral palsy and 157 controls (singleton term infants matched for gestational
      age and hospital of birth). CP was associated with tight nuchal cord overall
      (OR=2.8, 95% CI 1.1-6.8). Where cord around the neck is recorded at the
      discretion of the accoucheur (37 cases, 97 controls), there was an association
      between tight nuchal cord and CP (OR=5.4, 95% CI 1.4-20.4) and, in controls only,
      between Apgar score <7 at 1 min (OR=16.9, 95% CI 1.4-456.3). In the hospital
      where records included a tick box for nuchal cord (31 cases, 60 controls), an
      association between CP and tight nuchal cord could not be demonstrated (OR=1.4,
      95% CI 0.4-4.9). Nor was there an apparent association between nuchal cord and
      Apgar score <7 at 1 min (OR=2.6, 95% CI 0.4-15.9) in controls. CONCLUSIONS: The
      presence of nuchal cord is subject to recording bias. In a retrospective study,
      this can lead to an association of CP with nuchal cord that is not evident where
      documentation is systematic.

PMID- 12191524
TI  - Fetal state concordance predicts infant state regulation.
AB  - Fetal state organization reflects the development of the central nervous system
      but may also portend individual differences in postnatal state organization. The
      goal of the present study was to determine the extent to which fetal state
      regulation, defined as the percentage of an observation period in which fetal
      heart rate and movement concordance was displayed, is associated with neonatal
      state regulation. Neonatal state regulation was evaluated through a standard
      neurobehavioral assessment at 2 weeks postpartum. Biobehavioral concordance was
      measured in 52 normally developing fetuses at 24, 30 and 36 weeks gestation using
      an actocardiograph; the neonatal assessment was administered to 41 of these as
      infants. Intrafetal stability in biobehavioral concordance did not emerge prior
      to 36 weeks. Fetuses with higher concordance at 36 weeks were infants that
      displayed better state regulation during the exam, including more alertness and
      orientation (r(35)=0.29), less cost of maintaining attention (r=0.36), less
      irritability (r=-0.41), better regulatory capacity (r=0.47), a greater range of
      available states (r=0.34), and were significantly more likely to maintain control
      during the most aversive portions of the exam F(1,31)=4.63, p<0.05). These
      results support fetal state as a stable individual attribute that is conserved
      across the prenatal and neonatal periods.

PMID- 12191526
TI  - The ratio of second to fourth digit lengths: a marker of impaired fetal growth?
AB  - BACKGROUND: Epidemiological studies showing that impaired fetal growth has long
      term adverse health consequences have depended on crude measures of fetal growth
      such as overall weight or length. For future studies, there is a need to develop
      improved morphological markers of fetal growth which persist into adult life.
      Recent studies have suggested that the ratio of the length of the second finger
      relative to the length of the fourth finger (2D:4D ratio) is determined during
      fetal life and may be such a marker. AIMS: To determine whether the 2D:4D ratio
      is associated with size at birth. DESIGN: Cohort study. SUBJECTS: 139 men and
      women born in Preston, Lancashire between 1935 and 1943. OUTCOME MEASURES:
      Measurements of the 2D:4D ratio in palm prints. RESULTS: Men who had an above
      average placental weight and a shorter neonatal crown-heel length had higher
      2D:4D ratios in adult life. CONCLUSIONS: These preliminary findings lend support
      to the hypothesis that the 2D:4D ratio is determined during fetal life.

PMID- 12191527
TI  - Can spontaneous movements be modulated by visual and acoustic stimulation in 3
      month-old infants?
AB  - BACKGROUND: The assessment of the quality of general movements (GMs) in infants
      proves to be a reliable and valid diagnostic tool for detecting brain dysfunction
      early in life. Of special interest, particularly for the prediction of cerebral
      palsy, is the fidgety kind of GMs, the so-called fidgety movements (FMs)
      observable in 3- to 5-month-old infants. GMs are part of an infant's spontaneous
      motor repertoire and as such endogenously generated by the nervous system itself.
      AIM: The question was raised as to what extent the temporal organisation of FMs
      can be modulated by visual and acoustic stimulation. STUDY DESIGN: Spontaneous
      motility in supine position with and without stimulation was recorded on video
      and the data were semiquantitatively analysed. We studied the effect of visual
      stimulation (red ring, red puppet), unanimated acoustic stimulation (68, 77, 88
      dB) and of the mother, approaching her infant in a talkative manner after an
      absence of a quarter of an hour. SUBJECTS: Twenty-nine healthy infants at the age
      of 12 weeks who all showed normal FMs. RESULTS: Visual stimulation demonstrated
      that only the presentation of a red puppet elicited a significant level of
      focussed attention and led to a decrease of FMs. A red ring, unanimated acoustic
      stimulation as well as the interaction with the mother had no influence on the
      temporal organisation of FMs. CONCLUSION: This study demonstrated that in 3-month
      old infants, FMs is a predominant motor pattern and that it is possible to assess
      FMs during (playful) social interaction.

PMID- 12191528
TI  - Adoption and the effect on children's development.
AB  - Adoption, whether formal or informal, has always been a superior method of
      assuring survival for children whose parents are unwilling or unable to care for
      them. However, adoption can also affect child development in profound ways. Data
      collected over the past three decades support adoption as a superior means of
      promoting normal development in children permanently separated from birth
      parents. Out of calamity and loss, children recover and progress to become
      functionally and emotionally competent adults. For children suffering severe
      neglect or abuse in early life, an adoptive family is a remarkable environment
      for healing emotional and physical trauma and reversing developmental deficits.

PMID- 12191529
TI  - Difference between left and right lateral ventricular sizes in neonates.
AB  - The objective of this study is to determine the causes of asymmetry of the
      lateral ventricles in neonates. We also studied the effect of head position and
      the relationship of body weight at birth in regard to lateral ventricular size.
      Eligible for inclusion in this study were 60 neonatal infants whose gestational
      age was 33.1+/-3.5 weeks and whose birth weight was 1793+/-613 g.
      Ultrasonographic examinations were performed at the first and the second weeks
      after birth. In parasagittal and coronal scans through the posterior horn of the
      lateral ventricle, the lateral ventricle was traced and its area was measured. We
      found no significant variation of ventricular size in relation to body weight at
      birth. The left ventricular size was larger than the right one. The difference of
      the left and right ventricular sizes was partially effected by head position. The
      ratio of left to right lateral ventricular sizes showed a very wide distribution.
      We considered that ventricular asymmetry is not pathological, but due to
      individual differences.

PMID- 12191531
TI  - Sexual behaviour of second generation Moroccan immigrants balancing between
      traditional attitudes and safe sex.
AB  - Young Moroccan Islamic immigrants are balancing the challenges of modern society
      and the influences of their cultural and social backgrounds. Prevention and
      information programs need insights into their knowledge, attitudes and behaviour
      concerning choice of partner, sexuality, contraception, STD and AIDS prevention.
      In a qualitative research project, Moroccan adolescents were invited to focus
      groups. The results show the specific influence of family, religion and
      tradition, the importance of virginity at marriage for girls, and the "almost
      evidence" of premarital coitus for boys. These adolescents have limited knowledge
      of contraceptives, STD and AIDS. Some boys pretend to perform safe sex in certain
      "unfixed" circumstances but show no concern about the possible risks for future
      virgin spouses. Most of the girls do not consider safe sex before or after
      marriage. There is a taboo on homosexuality.

PMID- 12191532
TI  - Essential information and support needs of family caregivers.
AB  - The purpose of this study was to identify essential information and support needs
      of family caregivers for individuals with Alzheimer's disease or a related
      dementia, and to examine the relationship between caregiver characteristics and
      needs. Caregivers (n=128, response rate=49.4%) returned a survey detailing
      information needs, support needs, and personal information. The need for
      information concerning diagnosis/treatment and legal/financial issues was more
      important than general information about the disease. Specifically, information
      about health plan coverage was most important. Experienced caregivers also needed
      legal/financial information, as well as support. Female caregivers rated needs
      related to support as significantly more important than male caregivers.
      Practitioners should realize that caregivers may have different information and
      support needs and these needs may change throughout the caregiving experience.

PMID- 12191533
TI  - Nurse-patient power relationship: preliminary evidence of patients' power
      messages.
AB  - The interactive relationship that is based on sharing power and control is the
      goal of health counseling practice. This research examined the nurse-patient
      power relationship and emphasized the patient's perspective. Health counseling
      sessions, 38 in number, were videotaped, transcribed verbatim, and analyzed by
      using an adaptation of conversation analysis (CA). The purpose of this research
      was to describe in detail how patients' minimized power asymmetry during hospital
      counseling. The results indicate that power is a complex and polysemic phenomenon
      that can be created jointly. Nurses' power is associated with their medical
      knowledge, which also patients construct. However, patients have several options
      to construct their power and influence the flow of interaction, for example,
      directing the counseling with questions, interruptions, and extensive disclosure,
      in which also nurses participated. The results are discussed in terms of earlier
      research on power messages and implications for a future power sharing practice.

PMID- 12191534
TI  - Consumption, knowledge and attitudes of high school pupils towards alcohol and
      alcoholism: the Israeli experience.
AB  - Five hundred nine high school pupils from Holon (a city in the center of Israel)
      were surveyed about their consumption, knowledge and attitudes towards alcohol
      use and alcohol dependence. Two hundred fifty-nine pupils attended a vocational
      high school and 253 attended an academic high school. Forty percent of the pupils
      attending the academic school reported that they had drank beer between one to
      nine times during the last 2 months. In comparison with 72% of the vocational
      pupils, 42% of the academic pupils and 47% of the vocational pupils drank other
      alcoholic beverages (such as hard liquor, cognac, whisky or vodka) between one to
      nine times during the last 2 months. Boys drank alcohol more frequently than
      girls did. An earlier mean age of beer consumption was found among pupils in the
      vocational schools-12.8 years; as opposed to pupils in the academic school-13.4
      years. Knowledge of most pupils concerning alcoholic beverages and its potential
      harmful effects was lacking and pupils in the academic school showed a higher
      level of knowledge in comparison with the vocational pupils. Pupils in the
      vocational school had more liberal attitudes concerning recurrent consumption of
      alcoholic beverages than pupils in the academic school. Among the three leading
      reasons for drinking in the two schools were helping foster a sense of belonging,
      wish to feel like an adult and desire to forget daily anxieties and conflicts.
      Pupils in vocational schools are a target population with a higher risk for
      consuming alcoholic beverages. Discussion groups should be held in school and
      include personal stories of recovering alcoholics.

PMID- 12191535
TI  - Patients' waiting time at an outpatient clinic in Nigeria--can it be put to
      better use?
AB  - This study examined the usual activities of patients and the activities patients
      would favor during waiting time at the General Outpatients' (GOP) Clinic,
      University College Hospital (UCH), Ibadan, Nigeria. The potential of utilizing
      the waiting time for health education was also explored. A sample of 315 subjects
      selected using the systematic random sampling approach of one in five subjects
      attending the clinic over a period of 3 months were interviewed. The three most
      common activities patients engaged in during waiting time were watching of
      happenings in the clinic, reading and chatting. However, the most desired
      activity during waiting period was health education on specific diseases, which
      is to be presented as health talk by health personnel. The provision of health
      education on specific health issues constitutes an acceptable and useful way of
      utilizing waiting time in the outpatient clinic. This may further improve the
      health education services provided at such a clinic.

PMID- 12191536
TI  - How physicians experience patient consultations at an orthopaedic out-patient
      clinic: a qualitative study.
AB  - The aim of this study is to describe physicians' experiences in their encounters
      with patients by allowing the physicians to observe and comment on their own
      video-recorded medical consultations. Eighteen orthopaedic surgeons took part in
      the study; they were informed that we were interested in studying what actually
      takes place during a consultation, the quality of communication between doctor
      and patient, and how the physicians themselves experience the consultation. Each
      time the physician wished to make a comment, the video film was stopped and the
      comments were taped on audiocassette. The results showed that when the physicians
      watched the video-recorded consultations they commented spontaneously on issues
      regarding, among others: (1) how they try to adapt their communication to the
      patient's situation; (2) the need to explain things to the patient; (3)
      perceptions of working under unfavourable conditions; (4) difficulties in helping
      certain patients.

PMID- 12191537
TI  - Conceptions on treatment and lifestyle in patients with coronary heart disease--a
      phenomenographic analysis.
AB  - Twenty-three patients with an acute event of coronary heart disease (CHD)
      received routine care including information about medication and lifestyle
      changes. They were interviewed after 1 year about their conceptions concerning
      drug treatment and lifestyle changes. The interviews were taped, transcribed and
      analysed using the phenomenographic approach. Conceptions were hierarchically
      categorised with regard to level of understanding. The results showed that the
      patients' understanding of the effects and health benefits of their treatment was
      superficial as judged on an informed layman level. The knowledge was fragmentary
      and mechanistic. Several misconceptions were revealed. Few answers related to
      prognostic benefits. However, a conception about effects of stopping drug intake
      was risk of relapse. Some patients considered fate and heredity as the main
      causes of CHD. Thus, our patients had not achieved an adequate understanding of
      CHD treatment. The level of knowledge was lower than anticipated.

PMID- 12191538
TI  - Parent-child factors and their effect on communicating BRCA1/2 test results to
      children.
AB  - The purpose of the present study was to evaluate the likelihood and the effect of
      parent-child factors on communicating about maternal genetic test results for
      breast/ovarian cancer risk. Subjects were 42 mothers enrolled in a hereditary
      breast cancer research program who reported on their interactions with 68 target
      children. Predictor variables (demographic, clinical, and psychological) were
      assessed at baseline after mothers participated in a comprehensive genetic
      counseling/education session and provided a blood sample for BRCA1/2 mutation
      analysis. Maternal communication of test results to children was assessed 1 month
      after mothers learned their mutation status. The rate of disclosure to pediatric
      age children was 53%. Older children were more likely to be informed of their
      mothers' test results than were younger children. Maternal disclosure of genetic
      test results to children was also more likely to occur in the presence of more
      open parent-child communication styles, though the act of disclosing did not
      appear to impact communication style. These findings suggest that in addition to
      developmental phase, family behavioral interactions and communication styles are
      strongly predictive of whether or not mothers choose to share cancer genetic risk
      information with their children.

PMID- 12191539
TI  - Knowledge about preventing and managing lymphedema: a survey of recently
      diagnosed and treated breast cancer patients.
AB  - Physical therapists, books and oncologist's staff were the most frequently cited
      sources of lymphedema prevention and management information in a telephone survey
      of 148 recently treated breast cancer patients. Awareness, current practice and
      intention to practice 13 recommended prevention behaviors were low, and
      variations in these indices and in information sources were observed between
      those reporting any swelling and those who did not. Citing radiation oncologists
      as an information source reflected significantly higher levels of awareness,
      practice and intention as compared to not citing them. Also, citing oncologists
      reflected lower scores on the three indices as compared to not citing them. The
      results suggest that lymphedema prevention and management information is not
      getting to breast cancer survivors in a timely fashion and underscore the urgent
      need to develop and implement appropriate educational strategies. Additionally,
      research into factors that could motivate survivors to practice the recommended
      behaviors is warranted.

PMID- 12191540
TI  - Predicting adherence to prophylactic medication in adolescents with asthma: an
      application of the ASE-model.
AB  - An explanatory framework, referred to as the attitude/social influence/self
      efficacy-model (ASE-model), was utilised to explain future self-reported
      adherence of adolescents to daily inhaled prophylactic asthma medication. The
      objective was to investigate the long-term influence of these earlier reported
      cognitive variables and other psychological and medical determinants on self
      reported adherence 1 year later. Data were collected, via a questionnaire, from
      86 adolescents with asthma (aged 11 through 18 years) recruited from outpatient
      clinics. Adherence was assessed by asking the patients to give themselves a
      report mark for adherence. The results of the multiple regression analyses showed
      that the three major ASE-variables were predictors of self-reported adherence to
      a moderate degree (R(2)=0.21). Previous self-reported adherence was found to be
      the best predictor of self-reported adherence to prophylactic asthma medication 1
      year later (R(2)=0.45). The results of this study could be useful in the
      development of interventions to enhance adherence to asthma medication. In
      future, such interventions should focus on feelings of shame about having asthma
      and promoting healthy habits, such as adherence to medication.

PMID- 12191541
TI  - Empowering patients: how to implement a diabetes passport in hospital care.
AB  - The purpose was to ascertain the views of patients with diabetes and patient care
      teams on the introduction of a recently developed diabetes passport in order to
      plan effective implementation. A semi-qualitative study by eight semi-structured
      focus group discussions with patient care teams and patients in four Dutch
      hospitals was organised. In total 29 patients participated (range five to nine
      per hospital). Patient care teams ranged from four to six participants. Each team
      included at least one specialised diabetic nurse and an internist. Taped views
      were transcribed and coded on the basis of a structured checklist. Various
      potential barriers to the implementation of the diabetes passport were found.
      Although patients recognized the diabetes passport as a handy tool, most of them
      expected starting problems and little co-operation from the internists; in this
      respect they rely more on the diabetes specialist nurse (DSN). Internists had
      mixed feelings about the diabetes passport. Lack of motivation and lack of time
      were important perceived barriers. The specialised diabetes nurses had the
      highest expectations of the diabetes passport and perceived themselves as those
      who would effectuate implementation. The main potential barriers to effective
      implementation of the diabetes passport were found in setting the agenda of the
      passport and fitting it into the organization of diabetes care. These barriers
      need to be considered when implementing the passport. The DSN could play an
      important part in its implementation.

PMID- 12191542
TI  - Barriers to the evidence-based patient choice (EBPC) consultation.
AB  - This study was conducted to explore barriers to the implementation of the
      'evidence-based patient choice' (EBPC) consultation in medical practice. The
      theory behind EBPC encompasses the idea that patients should be provided with
      evidence-based information in a way that facilitates their ability to make
      choices or decisions about their health care. Semi-structured interviews were
      conducted with purposively selected general practitioners (GPs) (n=11), hospital
      doctors (n=10), practice nurses (n=5), academics (n=11) and lay people (n=8).
      Qualitative analyses of participants' responses were conducted to identify key
      themes and categories. Lack of medical evidence per se and evidence relevant to
      individual patients were the most commonly reported barriers to the EBPC
      consultation. Other barriers included: doctors' attitudes, limited time for
      doctors to keep up with the evidence and to introduce evidence into the
      consultation; economic and resource constraints and a lack of technical resources
      and training to enable doctors to practice this type of approach.

PMID- 12191563
TI  - Commentary: targeting myelodysplastic syndromes.

PMID- 12191564
TI  - Relationship between CD4(+)/CD8(+) T cell ratio and T cell activation in multiple
      myeloma: reference to IL-16.
AB  - We found that the ratio of CD4(+) to CD8(+) T cells (CD4/CD8 ratio) was decreased
      in patients with multiple myeloma (MM) and that this decrease was significantly
      related to an increase of human leukocyte antigen (HLA)-DR expression by CD8(+)
      (but not CD4(+)) T cells (P<0.005). In addition, the serum level of interleukin
      (IL)-16 was significantly higher in stage III MM patients than in healthy
      controls (P<0.001). The decrease of CD4(+) T cells in MM may be mediated by
      activation of CD8(+) T cells derived cytokine IL-16. In addition, these T cell
      phenotypic changes and the IL-16 level appear to be useful indicators of disease
      activity.

PMID- 12191565
TI  - Bcr-Abl variants: biological and clinical aspects.
AB  - Bcr-Abl is an oncogene that arises from fusion of the Bcr gene with the c-Abl
      proto-oncogene. Three different Bcr-Abl variants can be formed, depending on the
      amount of Bcr gene included: p185, p210, and p230. The three variants are
      associated with distinct types of human leukemias. Examination of the signaling
      pathways differentially regulated by the Bcr-Abl proteins will help us gain
      better insight into Bcr-Abl mediated leukemogenesis.

PMID- 12191566
TI  - Pilot study of recombinant human soluble tumor necrosis factor receptor (TNFR:Fc)
      in patients with low risk myelodysplastic syndrome.
AB  - In low risk myelodysplastic syndrome (MDS), increased apoptosis of marrow cells
      is a reproducible finding. Cytokines may drive this apoptosis. Several studies
      have demonstrated elevated levels of tumor necrosis factor-alpha (TNF-alpha) in
      MDS. Soluble tumor necrosis factor receptor (TNFR:Fc) can eliminate biologically
      active TNF in vivo. This data provided the rationale for a clinical trial of
      TNFR:Fc in low risk MDS. Eligibility was limited to cytopenic MDS patients with <
      10% marrow blasts. Secondary MDS was an exclusion. The study design was to
      administer 25mg TNFR:Fc twice a week for 10 weeks. Toxicity did not exceed grade
      1. No responses were observed in the 10 treated patients and one had disease
      progression. At this dosing schedule, TNFR:Fc is unlikely to ameliorate
      cytopenias in low risk MDS.

PMID- 12191568
TI  - Effect of vinorelbine on the growth of human myeloma cell lines in vitro.
AB  - Vinorelbine (NVB) is a newly synthesized vinca alkaloid that has been used to
      treat advanced malignant diseases including lung adenocarcinoma and lymphoma. The
      effect of NVB on myeloma, however, is unknown. We therefore examined the effect
      of NVB on the growth of human myeloma cell lines (RPMI8226, U266 and KPMM2) using
      the trypan blue dye exclusion test and Alamar blue assay. NVB inhibited the
      growth of myeloma cells of all three cell lines dose-dependently and this effect
      was intensified when NVB was combined with dexamethasone at 1.0 x 10(-6)mol/l.
      Flow cytometric analysis using annexin V (AN) and 7-amino-actinomycin D (7AAD)
      showed that NVB-induced apoptosis of these myeloma cells in all the cell lines.
      NVB appears to be a potent inducer of apoptosis in myeloma cells, and might have
      some benefit in the treatment of myeloma patients.

PMID- 12191567
TI  - FLAG-IDA regimen (fludarabine, cytarabine, idarubicin and G-CSF) in the treatment
      of patients with high-risk myeloid malignancies.
AB  - Forty-five patients with high-risk myeloid malignancies (32 acute myeloid
      leukemia and 13 high-risk myelodysplastic syndromes) were treated with
      fludarabine, cytarabine, idarubicin, and G-CSF (FLAG-IDA). Twenty-four (53%)
      patients achieved complete remission (CR), and five (11%) partial remission.
      Infection predominantly with pulmonary involvement was the most common regimen
      related toxicity. Mucositis (15 patients) and pulmonary toxicity (19 patients)
      were the most frequently observed non-hematologic side effects. There were four
      early deaths and 12 patients presented with resistant disease. Overall survival
      (OS) at 12 months was 40%. The FLAG-IDA regimen shows evident antileukemic
      activity in patients with high-risk myeloid malignancies with acceptable
      toxicity.

PMID- 12191569
TI  - The Bcl6 locus is not mutated in mouse B-cell lineage lymphomas.
AB  - In normal human germinal centre (GC) B-cells and post-GC B-cell lymphomas, a
      region in the first intron of the BCL6 gene, termed the major mutations cluster
      (MMC) exhibits somatic point mutations and deletions with patterns very similar
      to those seen in the variable regions of immunoglobulin (Ig) genes. In studies of
      mouse post-GC diffuse large cell lymphoma, Burkitt lymphomas, and plasmacytomas,
      direct sequencing or cold SSCP analyses revealed no mutations within a 686-bp
      region in Bcl6 intron 1 with 72% identity to the human MMC. The mouse Bcl6 locus
      must be inaccessible to the mutational machinery responsible for somatic
      mutations of Ig and BCL6 in humans.

PMID- 12191570
TI  - Human B-cell lymphoma cell lines are highly sensitive to apoptosis induced by all
      trans retinoic acid and interferon-gamma.
AB  - When cells were incubated in the presence of both interferon-gamma (IFN-gamma)
      and all-trans retinoic acid (ATRA), the concentration of IFN-gamma required to
      induce apoptosis of B-cell lymphoma cells was much lower than that required for
      myeloid or erythroid cell lines. The concentration of IFN-gamma that effectively
      inhibited the proliferation of BALM-3 cells was 1/40 of that required for BALM-1
      cells. STAT-1 phosphorylation, IRF-1 mRNA and protein expression and RAR-beta
      expression were enhanced to a greater degree in BALM-3 cells treated with IFN
      gamma and ATRA than in BALM-1 cells treated with IFN-gamma and ATRA, suggesting
      that these IFN-gamma related genes were involved in the induction of apoptosis of
      BALM-3 cells.

PMID- 12191571
TI  - Engineered fusion hybrid vaccine of IL-4 gene-modified myeloma and relative
      mature dendritic cells enhances antitumor immunity.
AB  - Dendritic cell (DC)-tumor fusion hybrid vaccine which facilitates antigen
      presentation represents a new powerful strategy in cancer therapy. In the present
      study, we investigated the antitumor immunity derived from vaccination of fusion
      hybrids between wild-type J558 or engineered J558-IL-4 myeloma cells secreting
      cytokine interleukin-4 (IL-4) and immature DCs (DC(IMAT)) or relative mature DCs
      (DC(RMAT)). DC(RMAT) displayed an up-regulated expression of immune molecules
      (Ia(d), CD40, CD54, CD80 and CD86) and certain cytokines/chemokines, and enhanced
      ability of allogeneic T cell stimulation when compared to DC(IMAT). These DCs
      were fused with myeloma cells by polyethylene glycol (PEG). The fusion efficiency
      was approximately 20%. Our data showed that immunization of C57BL/6 mice with
      DC(RMAT)/J558 hybrids induced protective immunity against a high dose of J558
      tumor challenge (1x10(6) cells) in 3 out of 10 immunized mice, compared with no
      protection seen in mice immunized with DC(IMAT)/J558 hybrids. Furthermore,
      immunization of mice with engineered DC(RMAT)/J558-IL-4 hybrids elicited stronger
      J558 tumor-specific cytotoxic T lymphocyte (CTL) responses in vitro and induced
      more efficient protective immunity (10/10 mice; tumor free) against J558 tumor
      challenge in vivo than DC(RMAT)/J558 hybrid vaccines. The results demonstrate the
      importance of DC maturation in DC-tumor hybrid vaccines and indicate that the
      engineered fusion hybrid vaccines which combine gene-modified tumor and DC
      vaccines may be an attractive strategy for cancer immunotherapy.

PMID- 12191572
TI  - Detection of increased icb-1 transcript levels in maturing HL-60 cells: a novel
      marker for granulocytic and monocytic in vitro differentiation.
AB  - Human gene icb-1 was initially described as a gene with increased expression in
      endometrial tumor cells differentiated in vitro by culture on a reconstituted
      basement membrane. We provide evidence for a more general involvement of icb-1
      gene function in cellular differentiation processes. We report the up-regulation
      of icb-1 transcript levels in HL-60 promyelocytic leukemia cells during their in
      vitro differentiation induced by all-trans retinoic acid, vitamin D(3) or DMSO.
      Increased icb-1 mRNA levels could be observed both in monocytic and granulocytic
      differentiation. We also report the identification of the novel icb-1 splice
      variants icb-1beta and gamma, and the spleen-specific isoform icb-1delta.
      Expression of icb-1 can be used as a novel marker for in vitro differentiation
      processes of HL-60 cells.

PMID- 12191573
TI  - Lymphoid blastic crisis of chronic myelogenous leukaemia with inv(16)(p13;q22).
AB  - We report a case of chronic myelogeneous leukaemia (CML) in B-lineage lymphoid
      blastic crisis (BC) having chromosome abnormality, inv(16)(p13;q22) in addition
      to Philadelphia chromosome, in 20/20 marrow metaphase. Inv(16)(p13;q22) was not
      observed in cells of chronic phase or accelerate phase. Abnormalities of
      chromosome 16, including inv(16)(p13;q22), del(16)(q22) and t(16;16)(p13;q22),
      have been reported mostly in acute myelomonocytic leukaemia (AML), (FAB M4-Eo),
      and some in CML-BC and myelodysplastic syndrome (MDS) cases. Most of the cases
      showed increase of myelomonocytic components and abnormal eosinophils with
      dysplastic granules in the bone marrow (BM). However, our case was diagnosed as
      lymphoid BC without increase of myelomonocytic components, although some abnormal
      eosinophilia was seen. To date, lymphoid BC of CML having inv(16)(p13;q22)
      abnormality has not been reported. The case presented here could be a clue to
      understand the pathophysiology of inv(16)(p13;q22) leukaemia.

PMID- 12191574
TI  - From chronic lymphocytic leukemia to Hodgkin's disease: a case of prognostically
      favorable transformation.

PMID- 12191576
TI  - Mesangial cells but not hepatocytes are protected against NO/O(2)(-)
      cogeneration: mechanistic considerations.
AB  - Reactive oxygen and nitrogen species such as superoxide (O(2)(-)) and nitric
      oxide (NO) are produced under diverse conditions and provoke distinct signaling
      reactions. The formation of NO has been shown to induce apoptosis and/or necrosis
      in mesangial cells and to protect other cells such as hepatocytes. Often, NO and
      O(2)(-) are simultaneously generated, which results in their diffusion-controlled
      interaction and, thus, redirects the signaling properties of either NO or O(2)(
      ). This has been proven for mesangial cells, where O(2)(-) formation attenuates
      NO-initiated apoptosis. As the mechanisms involved remained unclear, we studied
      the potential impact of the glutathione redox system and compared the results
      obtained with mesangial cells with those obtained with Hep G2 hepatocytes. In
      contrast to mesangial cells, Hep G2 cells appeared resistant to NO donors but
      displayed massive cell destruction following NO/O(2)(-) cogeneration. As a
      result, we noticed a greater increase in GSSG levels in Hep G2 cells than in
      mesangial cells. GSH depletion reversed the cell protection in mesangial cells
      and enhanced the cell damage in Hep G2 cells. NO/O(2)(-)-mediated mesangial
      protection is associated with an increased glutathione reductase activity and an
      increase in GSH. In conclusion, NO/O(2)(-) sensitivity is cell type specific and
      is determined by the glutathione redox system.

PMID- 12191577
TI  - Effects of clomipramine on neuronal nicotinic acetylcholine receptors.
AB  - The action of the tricyclic antidepressant clomipramine on membrane currents
      elicited by acetylcholine was studied in Xenopus oocytes expressing neuronal
      alpha2beta4 nicotinic acetylcholine receptors. Clomipramine inhibited the
      acetylcholine responses rapidly and reversibly, with a similar IC(50) when the
      oocytes were preincubated with clomipramine (1.3+/-0.2 microM) or when they were
      exposed simultaneously with acetylcholine and clomipramine (1.5+/-0.3 microM).
      The EC(50) was 39.9+/-2.1 microM for acetylcholine alone and 65.7+/-3.6 microM
      for acetylcholine in the presence of 2 microM clomipramine. The inhibitory effect
      of clomipramine was weakly voltage-dependent, with an electric distance of
      approximately 0.14. Moreover, clomipramine increased the rate of decay of
      currents elicited by acetylcholine. From all of these, we conclude that
      clomipramine reversibly and noncompetitively regulates neuronal alpha2beta4
      nicotinic acetylcholine receptors by blocking the open receptor-channel complex
      at a site close to the extracellular vestibule of the channel. The actions of
      clomipramine on neuronal nicotinic acetylcholine receptors may play an important
      role in the treatment of mental depression and other mood disorders.

PMID- 12191579
TI  - Activation of IP and EP(3) receptors alters cAMP-dependent cell migration.
AB  - Migration of vascular smooth cells from the media to the intima essentially
      contributes to neointima formation after percutaneous transluminal angioplasty
      and stent implantation. The stable prostacyclin mimetic iloprost has been shown
      to inhibit neointima formation in experimental restenosis, but it is currently
      unknown whether this may be caused by an antimigratory effect. Hence, the present
      study analyses (i) the influence of G(s)-coupled prostacyclin (IP) receptors on
      cell migration and (ii) verifies whether EP(3) receptors with opposite (i.e.,
      G(i)) coupling may conversely stimulate cell migration. In a modified Boyden
      chamber model, it was shown that iloprost dose-dependently inhibits the migration
      of primary human arterial smooth muscle cells, which constitutively express the
      IP receptor. On the other hand, human arterial smooth muscle cell migration was
      stimulated by the EP(3) receptor agonist M&B 28.767. To independently study the
      effects of these receptors, IP or EP(3) receptors were stably overexpressed in
      chinese hamster ovary cells (CHO-IP and CHO-EP(3)). Chemotaxis of CHO cells
      transfected with G(s)-coupled IP receptors was concentration-dependently
      inhibited by iloprost (2-100 nM), while there was no effect of iloprost on mock
      transfected CHO. By contrast, CHO-cells that overexpressed EP(3) receptors showed
      a significant, concentration dependent (1-100 nM) increase of cell migration in
      presence of the selective EP(3) agonist M&B 28.767. It is concluded that the
      prostacyclin mimetic iloprost inhibits vascular cell migration, which probably
      depends on a G(s)-mediated increase of intracellular cAMP. EP(3) receptors
      conversely stimulate CHO migration.

PMID- 12191578
TI  - Ca(2+)-dependent and -independent Cl(-) secretion stimulated by the nitric oxide
      donor, GEA 3162, in rat colonic epithelium.
AB  - The lipophilic nitric oxide-liberating drug, 1,2,3,4-oxatriazolium,5-amino-3-(3,4
      dichlorophenyl)-chloride (GEA 3162), concentration-dependently induced a Cl(-)
      secretion in rat colon. At a low concentration (5 x 10(-5) M), the action was
      Ca(2+)-dependent, whereas at a high concentration (5 x 10(-4) M), the response
      was independent from extracellular Ca(2+). Fura-2 experiments at isolated colonic
      crypts revealed that GEA 3162 induced an increase of the cytoplasmic Ca(2+)
      concentration due to an influx of extracellular Ca(2+), probably mediated by an
      activation of a nonselective cation conductance as demonstrated by whole-cell
      patch-clamp studies. After depolarization of the basolateral membrane, GEA 3162
      (5 x 10(-4) M) stimulated a current, which was suppressed by glibenclamide but
      was resistant against blockade of protein kinases by staurosporine, suggesting an
      activation of apical Cl(-) channels directly by the nitric oxide (NO) donor.
      After permeabilizing the apical membrane with the ionophore, nystatin, GEA 3162
      (5 x 10(-4) M) activated basolateral K(+) conductances and the Na(+)-K(+)-ATPase.
      Thus, the lipophilic NO donor GEA 3162 stimulates a Cl(-) secretion in a Ca(2+)
      dependent and -independent manner.

PMID- 12191580
TI  - Pteropodine and isopteropodine positively modulate the function of rat muscarinic
      M(1) and 5-HT(2) receptors expressed in Xenopus oocyte.
AB  - Pteropodine and isopteropodine are heteroyohimbine-type oxindole alkaloid
      components of Uncaria tomentosa (Willd.) DC, a Peruvian medicinal plant known as
      cat's claw. In this study, the effects of these alkaloids on the function of
      Ca(2+)-activated Cl(-) currents evoked by stimulation of G protein-coupled
      muscarinic M(1) acetylcholine and 5-HT(2) receptors were studied in Xenopus
      oocytes in which rat cortex total RNA was translated. Pteropodine and
      isopteropodine (1-30 microM) failed to induce membrane current by themselves.
      However, these alkaloids markedly enhanced the current responses evoked by both
      acetylcholine and 5-hydroxyhyptamine (5-HT) in a concentration-dependent and
      reversible manner with the maximal effects at 30 microM. Pteropodine and
      isopteropodine produced 2.7- and 3.3-fold increases in the acetylcholine response
      with EC(50) values of 9.52 and 9.92 microM, respectively, and 2.4- and 2.5-fold
      increases in the 5-HT response with EC(50) values of 13.5 and 14.5 microM,
      respectively. In contrast, in oocytes injected with total RNA from the rat
      cerebellum or spinal cord, neither alkaloid had an effect on the metabotropic
      current responses mediated by glutamate receptor(1 and 5) (mGlu(1/5)) receptors
      or ionotropic responses mediated by N-methyl-D-aspartate, kainic acid or glycine.
      Pteropodine and isopteropodine (10 microM) significantly reduced the EC(50)
      values of acetylcholine and 5-HT that elicited current responses, but had no
      effect on the maximal current responses elicited by acetylcholine and 5-HT. On
      the other hand, mitraphylline, a stereoisomer of pteropodine, failed to modulate
      acetylcholine- and 5-HT-induced responses. These results suggest that pteropodine
      and isopteropodine act as positive modulators of muscarinic M(1) and 5-HT(2)
      receptors.

PMID- 12191581
TI  - Involvement of ATP-sensitive K(+) channels in the peripheral antinociceptive
      effect induced by dipyrone.
AB  - We evaluated the effect of several K(+) channel blockers on the peripheral
      antinociception induced by dipyrone using the rat paw pressure test, in which
      sensitivity is increased by intraplantar injection (2 micro g) of prostaglandin
      E(2). Dipyrone administered locally into the right hindpaw (50, 100 and 200 micro
      g) elicited a dose-dependent antinociceptive effect which was demonstrated to be
      local, since only higher doses produced an effect when injected in the
      contralateral paw. The specific blockers of ATP-sensitive K(+) channels
      glibenclamide (40, 80 and 160 micro g/paw) and tolbutamide (80, 160 and 320 micro
      g/paw) antagonized the peripheral antinociception induced by dipyrone (200 micro
      g/paw). Charybdotoxin (2 micro g/ paw), a blocker of large conductance Ca(2+)
      activated K(+) channels, and dequalinium (50 micro g/paw), a selective blocker of
      small conductance Ca(2+)-activated K(+) channels, did not modify the effect of
      dipyrone. This effect was also unaffected neither by intraplantar administration
      of non-specific voltage-dependent K(+) channel blockers tetraethylammonium (1700
      micro g) and 4-aminopyridine (100 micro g) nor cesium (500 micro g), a non
      specific K(+) channel blocker. These results suggest that the peripheral
      antinociceptive effect of dipyrone may result from activation of ATP-sensitive
      K(+) channels, while other K(+) channels appear not to be involved in the
      process.

PMID- 12191582
TI  - Role of spin trapping and P2Y receptor antagonism in the neuroprotective effects
      of 2,2'-pyridylisatogen tosylate and related compounds.
AB  - 2,2'-Pyridylisatogen tosylate (PIT) is both an allosteric modulator of P2Y
      receptors, and an immine oxide, acting as a spin trap for free radicals. PIT (10
      mg kg(-1), i.p.) was found to be a powerful neuroprotective agent in protecting
      against the lesions induced by 15 micro g S-bromo-willardiine injected into the
      cortex or white matter of 5-day-old mice pups. As the multiple effects of PIT may
      induce both beneficial and deleterious effects, a reanalysis of the structure
      activity relationship was undertaken. PIT (50 micro M) and 2,3'-pyridylisatogen
      were potent antagonists of responses to ATP in the taenia preparation of the
      guinea-pig caecum, but 2,3'-nitrophenylisatogen was not. The reactive immine
      oxide group could be substituted by a keto moiety (N-(2'-pyridyl)phthalide) while
      maintaining antagonism of responses to ATP, equivalent to PIT. Thus, antagonism
      of P2Y receptors was not restricted to the isatogen nucleus. Other spin traps did
      not antagonise P2Y receptors, although dimethyl-pyrroline-N-oxide (DMPO)
      increased the sensitivity of responses to ATP. Both N-(2'-pyridyl)phthalide and
      2,3'-nitrophenylisatogen was less neuroprotective than PIT (10 mg kg(-1), i.p.)
      in protecting against the S-bromo-willardiine-induced lesions in mice, implying
      that both antagonism of P2Y receptors and the immine oxide moiety may be
      important for the neuroprotective effects of PIT. However, the usefulness of the
      neuroprotection was limited because, in motoneurones obtained from rat embryos,
      PIT (10-100 micro M) exacerbated cell death.

PMID- 12191584
TI  - Effect of the amisulpride isomers on rat catalepsy.
AB  - The substituted benzamide amisulpride is currently administered in its racemic
      form. In the present study, the biochemical and cataleptogenic profiles of the
      two enantiomers (R+ and S-) were compared with those of the racemic mixture.
      Displacement binding studies showed that the (S-)-isomer possesses an higher
      affinity for dopamine D2-like receptor (K(i) 5.2+/-0.4 nM) compared to (R+)
      amisulpride (K(i) 244+/-12 nM) and to (RS)-amisulpride (K(i) 9.8+/-0.8 nM). In
      contrast, (S-)-amisulpride binds the alpha(2)-receptor with an affinity (K(i)
      1528+/-45 nM) lower than that of the (R+)-isomer (K(i) 375+/-34 nM) and of (RS)
      amisulpride (K(i) 783+/-27 nM). The bar test was used to evaluate the catalepsy
      induced by each drug. (RS)-amisulpride induced catalepsy only at very high doses
      (>100 mg/kg, s.c.) whereas, (S-)-amisulpride produced a catalepsy at a lower dose
      (30 mg/kg, s.c.) and (R+)-amisulpride did not produce any catalepsy up to the
      dose of 75 mg/kg. Interestingly, (R+)-amisulpride reduced the catalepsy induced
      by (S-)-amisulpride (50 mg/kg, s.c.) or haloperidol (0.3 mg/kg, s.c.), at the
      doses of 50 or 30 mg/kg, respectively. These results indicate that the weak
      cataleptic properties of (RS)-amisulpride might partially rely on its (R+)-isomer
      and provide a further explanation for the atypical properties of amisulpride as
      an antipsychotic.

PMID- 12191583
TI  - In vitro neuronal and vascular responses to 5-hydroxytryptamine: modulation by 4
      methylthioamphetamine, 4-methylthiomethamphetamine and 3,4
      methylenedioxymethamphetamine.
AB  - 4-Methylthioamphetamine and 4-methylthiomethamphetamine are thioarylethylamines
      structurally related to 3,4-methylenedioxymethamphetamine (MDMA, 'Ecstasy'). This
      study compared effects of these agents and MDMA on 5-hydroxytryptamine (5-HT)
      signalling systems in the brain and vasculature in vitro. Both 4
      methylthioamphetamine and 4-methylthiomethamphetamine (100 micro M) reduced the
      rate of specific high affinity [3H]5-HT reuptake in isolated rat brain
      synaptosomes to 14% and 10% of control, respectively. The concentration required
      for half-maximal inhibition (IC(50)) of [3H]5-HT reuptake by 4
      methylthioamphetamine (0.27 micro M) was significantly lower (P<0.005) than that
      for inhibition by MDMA (1.28 micro M) and that for inhibition by 4
      methylthiomethamphetamine (0.89 micro M). Both 4-MTA and 4-MTMA caused a
      significant release of preloaded [3H]5-HT from synaptosomes, but were
      significantly less effective than MDMA at the concentrations tested (1-100 micro
      M). In isolated rat aorta, a 15-min preincubation with 4-methylthioamphetamine or
      4-methylthiomethamphetamine significantly reduced the maximal contraction
      (E(max)) induced by 5-HT to 71% or 91% of control (P<0.05 in each case),
      respectively. In addition, 4-methylthiomethamphetamine (100 micro M), but not 4
      methylthioamphetamine, significantly increased the concentration of 5-HT required
      for half-maximal contraction (EC(50)) from 4.13 to 20.08 micro M (P<0.0001). In
      contrast, MDMA did not significantly alter the E(max) or the EC(50) of 5-HT
      induced aortic contraction. It is concluded that both 4-methylthioamphetamine and
      4-methylthiomethamphetamine are potent inhibitors of [3H]5-HT reuptake in the
      brain. Furthermore, unlike MDMA, they both directly inhibit 5-HT-mediated
      vascular contraction. These results suggest that these compounds may be
      potentially more harmful than MDMA in the context of human misuse.

PMID- 12191585
TI  - Reduction of cerebral injury in stroke-prone spontaneously hypertensive rats by
      amlodipine.
AB  - Dihydropyridine Ca(2+) channel antagonists, initiated together with high salt
      intake, prevent the development of hypertension and subsequent cerebral damage in
      stroke-prone spontaneously hypertensive rats (SHRSP). We hypothesized that the
      dihydropyridine Ca(2+) channel antagonist amlodipine (approximately 15 mg/kg/day)
      could also reverse established hypertension and cerebral damage. SHRSP drank 1%
      NaCl from 8 weeks of age. Cerebral damage (cerebral edema and blood-brain barrier
      integrity) was investigated with magnetic resonance imaging twice a week.
      Systolic blood pressure was measured weekly. All rats developed severe
      hypertension and subsequent cerebral damage (defined as day 0). Untreated
      controls (n=7) died at day 12 (range: 7-28). Oral treatment with amlodipine
      (n=7), initiated at day 0, reduced systolic blood pressure, reversed cerebral
      edema and restored blood-brain barrier integrity. Systolic blood pressure
      remained low and eventually rats died after 450 days (range: 350-580) showing
      nephrosis but no recurrence of cerebral damage. In conclusion, established
      hypertension and cerebral damage are reversed by amlodipine in SHRSP.

PMID- 12191586
TI  - Effects of acamprosate and some polyamine site ligands of NMDA receptor on short
      term memory in rats.
AB  - The aim of this study was to evaluate the effect of multiple acamprosate (500.0
      mg/kg, p.o.) administration on short-term memory, using the social recognition
      test in rats. Ifenprodil (1.0 mg/kg, i.p.), arcaine (5.0 mg/kg, i.p.) and
      spermidine (20.0 mg/kg, i.p.) were chosen as polyamine ligands and their action
      or interaction with acamprosate was also studied. The doses used did not show any
      sedative activity, which was assessed by measuring locomotor activity and the
      hypnotic effect of ethanol. The findings suggest that acute acamprosate treatment
      did not impair short-term memory. Multiple acamprosate and a single spermidine or
      arcaine administration led to better performance in the memory test, whereas no
      significant difference was observed in ifenprodil-treated rats. Co-administration
      of a single arcaine or spermidine dose with multiple acamprosate produced worse
      results. This means that the effect of repeated acamprosate administration can be
      changed by the co-administration of other polyamine ligands, so that care should
      be taken in interpreting.

PMID- 12191587
TI  - Role of endothelium-derived relaxing factors in adrenomedullin-induced
      vasodilation in the rat kidney.
AB  - The present study aimed to evaluate the contributions of endothelium-derived
      hyperpolarizing factor (EDHF), the nitric oxide (NO)-cGMP pathway, and
      prostaglandins to adrenomedullin-induced vasodilation in isolated rat kidney.
      Inhibition of the NO-cGMP pathway with N(omega)-nitro-L-arginine methyl ester (L
      NAME) or 1H-[1,2,4]oxadiazolo-[4,3a]quinoxalin-1-one (ODQ) reduced the maximal
      vasodilator response to adrenomedullin by approximately 50%. Pretreatment of the
      vessels with the potassium channel inhibitor, tetraethylammonium or increased
      extracellular K(+), also decreased the maximal response to adrenomedullin by
      approximately 50%. The simultaneous administration of blockers of both
      endothelium-derived relaxing factors had a combined effect that almost suppressed
      adrenomedullin-induced vasodilation. The administration of indomethacin did not
      modify the renal response to adrenomedullin. Our results suggest that the
      vasodilator response to adrenomedullin in the isolated perfused kidney of rats is
      mediated by EDHF and NO to a similar extent. Our data also provide evidence that
      prostaglandins play no role in the vasodilator response to adrenomedullin in the
      renal vasculature.

PMID- 12191588
TI  - Relaxation induced by milrinone and rolipram in human penile arteries and veins.
AB  - We studied the relaxant effects of milrinone, an inhibitor of phosphodiesterase
      3, and rolipram, an inhibitor of phosphodiesterase 4, on contracted human penile
      dorsal artery and deep dorsal vein. Vascular rings from 12 multi-organ donors
      were suspended in organ baths for isometric recording of tension. Both milrinone
      and rolipram inhibited (100%) the contraction induced by noradrenaline and
      shifted the relaxation-response curves to the cAMP forming agents prostaglandin
      E(1) and forskolin to the left. The findings indicate that the cAMP pathway
      appears to be a main determinant of relaxation in human penile vessels.

PMID- 12191589
TI  - Triglyceride-lowering effect of pitavastatin [corrected] in a rat model of
      postprandial lipemia.
AB  - The triglyceride-lowering effect of pitavastatin, a potent 3-hydroxy-3
      methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitor, was investigated in a
      rat model of postprandial lipemia. Plasma triglyceride levels started to increase
      4 h after the fat load, reached the maximum at 6 h and then gradually decreased.
      A single dose of pitavastatin (1 mg/kg) significantly suppressed chylomicron
      triglyceride secretion into the lymph by 40% and delayed the elevation of plasma
      triglyceride. Pitavastatin at 1 mg/kg decreased the 6-h plasma triglyceride
      levels by 53% and at 0.5 mg/kg decreased the 0-12 h area under the curve (AUC) of
      triglyceride levels by 56%. Atorvastatin also caused decreases, but to a lesser
      extent. Pitavastatin, and atorvastatin to a lesser extent, reduced the activity
      of the intestinal microsomal triglyceride transfer protein (MTP) at 6 h. These
      results suggested that a single dose of pitavastatin lowered postprandial
      triglyceride levels in rats by decreasing chylomicron-triglyceride secretion,
      probably through a reduction of intestinal MTP activity and triglyceride droplet
      formation in the endoplasmic reticulum.

PMID- 12191590
TI  - Nicotine suppresses gastric wound repair via the inhibition of polyamine and K(+)
      channel expression.
AB  - Nicotine is one of the most representative components in cigarette smoke leading
      to gastric ulceration. Both ornithine decarboxylase and potassium ion (K(+))
      channels are essential for cell growth and wound repair. The aim of the present
      study is to elucidate the causative relationship of these two factors during
      wound healing and the influence of nicotine on this healing process in rat
      gastric mucosal epithelial cells (RGM-1). Nicotine markedly inhibited cell
      migration and proliferation in RGM-1 cells. The latter effect was significantly
      antagonized by a nicotinic receptor blocker, mecamylamine. Nicotine also
      suppressed ornithine decarboxylase activity significantly. Our data showed that
      inhibition of cell proliferation and ornithine decarboxylase activity by nicotine
      was accompanied with a reduction in K(+) channel protein expression, all of which
      were significantly alleviated by spermidine pretreatment. These results suggested
      that there was a cause/effect link between ornithine decarboxylase and K(+)
      channel on wound repair. Nicotine in cigarette smoke inhibited this healing
      process and delayed wound repair in gastric epithelial cells.

PMID- 12191592
TI  - Pharmacological importance of phospholipase D and phosphatidic acid in the
      regulation of the mitogen-activated protein kinase cascade.
AB  - The stimulation of cells with many extracellular agonists leads to the activation
      of phospholipase (PL)D. PLD metabolizes phosphatidylcholine to generate
      phosphatidic acid (PA). Neither the mechanism through which cell surface
      receptors regulate PLD activation nor the functional consequences of PLD activity
      in mitogenic signaling are completely understood. PLD is activated by protein
      kinase C, phospholipids, and small GTPases of the ADP-ribosylation factor and Rho
      families, but the mechanisms linking cell surface receptors to the activation of
      PLD still require detailed analysis. Furthermore, the latest data on the
      functional consequences of the generation of cellular PA suggest an important
      role for this lipid in the regulation of membrane traffic and on the activation
      of the mitogen-activated protein kinase cascade. This review addresses these
      issues, examining some novel models for the physiological role of PLD and PA and
      discussing their potential usefulness as specific targets for the development of
      new therapies.

PMID- 12191591
TI  - Kallikrein cascade and cytokines in inflamed joints.
AB  - Rheumatoid arthritis is a chronic multi-system disease of unknown aetiology. The
      current hypothesis is that an unknown antigen triggers an autoimmune response in
      a genetically susceptible individual. The predominant pathological change is that
      of an inflammatory synovitis, characterised by cellular infiltrates and
      angiogenesis, with subsequent bone and cartilage destruction. These pathological
      changes are as a result of the activation of a variety of cells, inflammatory
      mediators, and effector molecules. The pro-inflammatory kinins and cytokines
      appear to play a central role in the pathogenesis of rheumatoid arthritis.
      Sufficient evidence exists that establishes a key role for the kallikrein-kinin
      cascade in inflamed joints. In addition, there appears to be an inter
      relationship between cytokines and kinins in the inflammatory process. Kinins
      induce the release of cytokines, and cytokines have been shown to augment the
      effects of kinins. This may lead to an enhancement and perpetuation of the
      inflammatory process. In this review, we report a first study, correlating
      markers of disease with the kallikrein-kinin cascade and with cytokines.

PMID- 12191593
TI  - The physiology and pharmacology of the orexins.
AB  - Orexin-A and orexin-B are two peptides derived by proteolytic cleavage from a 130
      amino acid precursor prepro-orexin, which recently were isolated from the rat
      hypothalamus. Orexin-A is fully conserved across mammalian species, whilst rat
      and human orexin-B differ by 2 amino acids. These peptides bind to two G(q)
      coupled receptors, termed OX(1) and OX(2). The receptors are 64% homologous and
      highly conserved across species. Orexin-A is equipotent at OX(1) and OX(2),
      whilst orexin-B displays moderate ( approximately 10-fold) selectivity for OX(2).
      Prepro-orexin is found in the hypothalamus and, to a markedly lesser extent, the
      testes, adrenals, and myenteric plexus. However, orexin-A and orexin-B are found
      throughout the CNS, due to extrahypothalamic projections, as well as in the
      adrenals and small intestine. OX(1) is expressed mainly in the hypothalamus and
      locus coeruleus, as well as other brain regions and the spinal cord. OX(2) is
      expressed in the hypothalamus, cortex, spinal cord, and a few discrete brain
      nuclei. Both receptors are also expressed in the gut. The orexins modulate
      feeding behaviour and energy homeostasis, as well as associated drinking
      behaviours, and also regulate the sleep-wake cycle. Moreover, disruption of
      prepro-peptide expression or mutations in the gene encoding OX(2) result in a
      narcoleptic phenotye in various animal models, whilst several clinical studies
      have linked disruption of the orexin system to narcolepsy in humans. The orexins
      also have cardiovascular and neuroendocrine effects. This review further details
      the pharmacology and localisation of these peptides and summarises the evidence
      for their role in the physiology outlined above.

PMID- 12191594
TI  - The pharmacology of cardiac memory.
AB  - Cardiac memory is an altered T wave during sinus rhythm that is induced by a
      period of ventricular pacing or arrhythmia. The T wave is characterized by a
      vector that tracks that of the previously paced or arrhythmic QRS complex.
      Although initially considered a clinical oddity, cardiac memory is of interest
      both as an example of the general biological property of memory - as studied most
      extensively in neural tissues - and because of its implications regarding the
      control of cardiac rhythm. Signal transduction of cardiac memory appears to
      involve an angiotensin II-regulated pathway initiated by altered stress/strain
      patterns in the myocardium. The end result is altered density and kinetics of the
      transient outward current and perhaps other ion currents as well, and an altered
      transmural gradient for repolarization. The altered repolarization pattern is
      accompanied by altered responses to specific antiarrhythmic drugs that may be
      anti- or proarrhythmic.

PMID- 12191595
TI  - New insights into the molecular actions of serotonergic antimigraine drugs.
AB  - Migraine is a painful and debilitating neurological disorder that affects
      approximately 10% of the adult population in Western countries. Sensitization and
      activation of the trigeminal ganglia nerves that innervate the meningeal blood
      vessels is believed to play an important role in the initiation and maintenance
      of migraine pain. In this capacity, release of the neuropeptide calcitonin gene
      related peptide (CGRP) and the resultant neurogenic inflammation is thought to
      underlie the pathophysiology of migraine. Largely due to the success of the
      serotonin Type 1 migraine drugs such as sumatriptan, migraine pathology and
      therapy has become a focus of intensive clinical and physiological research
      during the past decade. The effectiveness of these drugs is thought to be due to
      their ability to block the stimulated secretion of neuropeptides from trigeminal
      nerves to break the vicious nociceptive cycle of migraine. A component of this
      nociceptive cycle involves activation of mitogen-activated protein kinase
      signaling pathways. Indeed, activation of mitogen-activated protein kinase
      pathways can increase CGRP neuropeptide synthesis and secretion. Recently, the
      serotonin Type 1 agonists have been shown to cause a prolonged increase in
      intracellular Ca(2+) in trigeminal ganglia neurons and an increased phosphatase
      activity that can repress stimulated CGRP secretion and transcription.
      Identification of molecular signaling events in migraine pathology and therapy
      has provided new insight into the pharmacology and signaling mechanisms of
      sumatriptan and related drugs, and may provide the foundation for development of
      novel treatments for migraine.

PMID- 12191596
TI  - Cholinergic innervation and function in the prostate gland.
AB  - The mammalian prostate is densely innervated by hypogastric and pelvic nerves
      that play an important role in regulating the growth and function of the gland.
      While there has been much interest in the role of the noradrenergic innervation
      and adrenoceptors in prostate function, the role of cholinergic neurones in
      prostate physiology and pathophysiology is not well understood. This review
      focuses on the role of acetylcholine and cholinoceptors in prostate function.
      Nitric oxide, vasoactive intestinal polypeptide, and/or neuropeptide Y are co
      localised with cholinesterase and/or acetylcholine transporter in some of the
      nerve fibres supplying the prostate. Their roles are also briefly discussed in
      this review. A dense network of cholinesterase-staining fibres supplies both
      prostate epithelium and stroma, suggesting a role of acetylcholine and/or co
      localised neuropeptides in the modulation of prostatic secretions, as well as
      smooth muscle tone. A predominantly epithelial location for prostate muscarinic
      receptors indicated a major secretomotor role for acetylcholine. The muscarinic
      receptor subtype mediating muscarinic agonist-induced smooth muscle contraction
      or enhancement of contractions evoked by nerve stimulation differs in different
      species. In the human, there is evidence for M(1) receptors on the epithelium,
      M(2) receptors on the stroma, and both M(1) and M(3) receptors in some prostate
      cancer cell lines. Several recent investigations indicate that muscarinic
      receptors may also mediate or modulate normal, benign, and malignant prostate
      growth. The role of muscarinic agonists and their receptors and the influences of
      age, testicular, and other steroids in regulating the effects are reviewed.

PMID- 12191597
TI  - Multiple roles of protein kinases in the modulation of gamma-aminobutyric acid(A)
      receptor function and cell surface expression.
AB  - gamma-Aminobutyric acid(A) (GABA(A)) receptors are ligand-gated ion channels that
      mediate the majority of fast synaptic inhibition in the brain and that are also
      important drug targets for benzodiazepines, barbiturates, and neurosteriods.
      These receptors are pentameric hetero-oligomers that can be assembled from 7
      subunit classes with multiple members: alpha(1-6), beta(1-3), gamma(1-3), delta,
      epsilon, theta, and pi. Most receptor subtypes in the brain, however, are
      believed to be composed of alpha-, beta-, and gamma-subunits. Modifications of
      GABA(A) receptor function are continually implicated in a range of pathologies,
      including epilepsy, anxiety, insomnia, and substance abuse. Moreover, changes in
      the efficacy of synaptic inhibition mediated by GABA(A) receptors are believed to
      be play central roles in certain forms of synaptic plasticity, including rebound
      potentiation in the cerebellum, and hippocampal long-term potentiation. Given the
      critical role that GABA(A) receptors play as mediators of synaptic transmission,
      it is of fundamental importance to understand the endogenous mechanisms used by
      neurones to control the function of these receptors. This review will focus on
      the dynamic regulation of GABA(A) receptor phosphorylation state and channel
      function as mechanisms involved in determining the efficacy of synaptic
      inhibition. In addition, the possible role of GABA(A) receptor phosphorylation in
      controlling receptor internalization and recycling will also be explored.

PMID- 12191598
TI  - Tumor necrosis factor-alpha in cardiovascular biology and the potential role for
      anti-tumor necrosis factor-alpha therapy in heart disease.
AB  - The functional role of tumor necrosis factor (TNF)-alpha in the heart has been
      extensively studied over the last 15 years. Collectively, these studies have
      demonstrated that TNF-alpha has both diverse and potentially conflicting roles in
      cardiac function and pathology. These include beneficial effects, such as
      cardioprotection against ischemia, myocarditis, and pressure overload, as well as
      potentially adverse effects, such as the development of atherosclerosis,
      reperfusion injury, hypertrophy, and heart failure. TNF-alpha antagonist therapy
      recently has been demonstrated to be clinically applicable in inflammatory
      conditions, and clinical trials are currently in progress in the use of these
      agents in cardiovascular diseases. The scope for clinical applications of anti
      TNF-alpha therapy in cardiovascular diseases is potentially extensive. Hence,
      this review has been undertaken to evaluate the cardiovascular effects of this
      pleiotropic cytokine and to evaluate the potential of targeting this cytokine in
      cardiovascular therapeutics. An overview of the TNF-alpha peptide and its
      associated signaling are described. This is followed by a discussion of the known
      roles of TNF-alpha in cardiac physiology and in a diverse array of cardiac
      pathologies. Reference to experimental and clinical studies using anti-TNF-alpha
      therapies are described where applicable. The postulated role of TNF-alpha
      signaling concerning innate cardiac cellular processes that may have direct
      adaptive effects in the heart will be reviewed with respect to future research
      directions. Finally, the author postulates that attenuation of TNF-alpha
      biosynthesis in selected individuals will need to be tested if true benefits of
      this therapeutic approach are to be realized in the management of cardiovascular
      diseases.

PMID- 12191599
TI  - Neurobiology of relapse to alcohol in rats.
AB  - Relapse to alcohol use after prolonged withdrawal periods is the major problem in
      the treatment of alcohol dependence in humans. However, until recently,
      relatively few preclinical studies concentrated on the elucidation of the
      neurochemical events underlying relapse to alcohol. In this article we will
      review recent data from studies in which alcohol-deprivation and reinstatement
      models were used to determine the mechanisms underlying relapse to alcohol in
      rats. In the alcohol-deprivation model, the intake of alcohol is determined after
      prolonged periods of forced abstinence in drug-experienced rats. In the
      reinstatement model, the ability of acute non-contingent exposure to drug or non
      drug stimuli to reinstate drug seeking is determined following training for drug
      self-administration and subsequent extinction of the drug-reinforced behavior. We
      will review studies, which used these preclinical models, on the effect of
      specific pharmacological agents on relapse to alcohol seeking induced by re
      exposure to alcohol and to alcohol-associated cues and by exposure to stress.
      Subsequently, we will describe potential neuronal circuits that may underlie
      relapse to alcohol. Finally, future directions and clinical implications of the
      study of relapse to alcohol in laboratory animals will be discussed briefly.

PMID- 12191600
TI  - K(+) channels as therapeutic drug targets.
AB  - K(+) channels play critical roles in a wide variety of physiological processes,
      including the regulation of heart rate, muscle contraction, neurotransmitter
      release, neuronal excitability, insulin secretion, epithelial electrolyte
      transport, cell volume regulation, and cell proliferation. As such, K(+) channels
      have been recognized as potential therapeutic drug targets for many years.
      Unfortunately, progress toward identifying selective K(+) channel modulators has
      been severely hampered by the need to use native currents and primary cells in
      the drug-screening process. Today, however, more than 80 K(+) channel and K(+)
      channel-related genes have been identified, and an understanding of the molecular
      composition of many important native K(+) currents has begun to emerge. The
      identification of these molecular K(+) channel drug targets should lead to the
      discovery of novel drug candidates. A summary of progress is presented.

PMID- 12191603
TI  - Structural aspects of protein kinase control-role of conformational flexibility.
AB  - Protein kinases catalyze the phosphotransfer reaction fundamental to most
      signaling and regulatory processes in the eukaryotic cell. Absolute control of
      individual protein kinase activity is, therefore, of utmost importance to
      signaling fidelity in the cell. Mechanisms for activity modulation, including
      complete and reversible inactivation, have been shown by crystal structures of
      many active and inactive protein kinases. The structures of inactivated kinases,
      compared with those of active and catalytically competent kinases such as the
      protein kinase A catalytic subunit, highlight recurring structural alterations
      among a set of elements of the catalytic kinase core. These 'activity modulation
      sites' apparently comprise the principal evolved mechanisms for control of enzyme
      activity in the catalytic domain. In combination, they enable diverse
      physiological regulatory mechanisms operative for most protein kinases.
      Identification and characterization of these sites should impact strategies for
      discovery and design of target-specific therapeutic drugs as the range of
      structural variations for specific kinases becomes known. The principle site, the
      ATP-binding pocket, is the target of many physiological regulators and also most
      experimental or therapeutic inhibitors, which typically block it in a competitive
      or allosteric fashion. Co-crystallization studies with protein kinase A and other
      kinases have revealed binding features of several classes of protein kinase
      inhibitors. Ligand-induced structural changes are common and tend to optimize
      buried surface areas. The ability to optimize binding energies arising from the
      hydrophobic effect creates a logarithmic dependence of binding energy on buried
      surface areas. Exceptions to this rule arise for specific inhibitor classes, and
      possibly also as artifacts of structure determination.

PMID- 12191602
TI  - Protein kinases as targets for anticancer agents: from inhibitors to useful
      drugs.
AB  - Many components of mitogenic signaling pathways in normal and neoplastic cells
      have been identified, including the large family of protein kinases, which
      function as components of signal transduction pathways, playing a central role in
      diverse biological processes, such as control of cell growth, metabolism,
      differentiation, and apoptosis. The development of selective protein kinase
      inhibitors that can block or modulate diseases caused by abnormalities in these
      signaling pathways is widely considered a promising approach for drug
      development. Because of their deregulation in human cancers, protein kinases,
      such as Bcr-Abl, those in the epidermal growth factor-receptor (HER) family, the
      cell cycle regulating kinases such as the cyclin-dependent kinases, as well as
      the vascular endothelial growth factor-receptor kinases involved in the neo
      vascularization of tumors, are among the protein kinases considered as prime
      targets for the development of selective inhibitors. These drug-discovery efforts
      have generated inhibitors and low-molecular weight therapeutics directed against
      the ATP-binding site of various protein kinases that are in various stages of
      development (up to Phase II/III clinical trials). Three examples of inhibitors of
      protein kinases are reviewed, including low-molecular weight compounds targeting
      the cell cycle kinases; a potent and selective inhibitor of the HER1/HER2
      receptor tyrosine kinase, the pyrollopyrimidine PKI166; and the 2-phenyl
      aminopyrimidine STI571 (Glivec(R), Gleevec) a targeted drug therapy directed
      toward Bcr-Abl, the key player in chronic leukemia (CML). Some members of the HER
      family of receptor tyrosine kinases, in particular HER1 and HER2, have been found
      to be overexpressed in a variety of human tumors, suggesting that inhibition of
      HER signaling would be a viable antiproliferative strategy. The pyrrolo
      pyrimidine PKI166 was developed as an HER1/HER2 inhibitor with potent in vitro
      antiproliferative and in vivo antitumor activity. Based upon its clear
      association with disease, the Bcr-Abl tyrosine kinase in CML represents the ideal
      target to validate the clinical utility of protein kinase inhibitors as
      therapeutic agents. In a preclinical model, STI571 (Glivec(R), Gleevec) showed
      potent in vitro and in vivo antitumor activity that was selective for Abl, c-Kit,
      and the platelet-derived growth factor-receptor. Phase I/II studies demonstrated
      that STI571 is well tolerated, and that it showed promising hematological and
      cytogenetic responses in CML and clinical responses in the c-Kit-driven
      gastrointestinal tumors.

PMID- 12191604
TI  - Structural studies with inhibitors of the cell cycle regulatory kinase cyclin
      dependent protein kinase 2.
AB  - Components of the cell cycle machinery are frequently altered in cancer. Many of
      these alterations affect the cyclin-dependent kinases (CDKs) and their
      regulation. Staurosporine and 7-hydroxystaurosporine (UCN-01) are two natural
      product kinase inhibitors originally identified as potent protein kinase C
      inhibitors. Staurosporine is non-selective and too toxic for use in therapy, but
      UCN-01 shows greater selectivity, and is in clinical trials. We have determined
      the crystal structures of staurosporine bound to monomeric CDK2 and UCN-01 bound
      to active phospho-CDK2/cyclin A. Both compounds mimic the hydrogen bonds made by
      the adenine moiety of ATP, and both exploit the non-polar nature of the adenine
      binding site. In the complex with UCN-01, a hydrogen-bonded water molecule is
      incorporated into the non-polar cavity, which provides a partial polar character
      in the environment of the 7-hydroxyl group. Comparison of the ATP-binding site of
      CDK2 with that of other kinases reveals that in Chk1 kinase, a major target for
      UCN-01 in the cell, one of the surrounding residues, Ala144 in CDK2, is a serine
      in Chk1, thus providing a possible explanation for the effectiveness of UCN-01
      against this kinase. For cells to exit mitosis, the CDKs must be completely
      inactivated, firstly by the ubiquintin-mediated destruction of the cyclins,
      followed by dephosphorylation of phospho-Thr160 (in CDK2) catalysed by the kinase
      associated phosphatase and protein phosphatase 2C. We describe the structure of
      phospho-CDK2 in complex with kinase-associated phosphatase, and discuss the
      substrate recognition promoted by interactions that are remote from the catalytic
      site.

PMID- 12191606
TI  - Cyclin-dependent kinases as potential targets to improve stroke outcome.
AB  - Increasing evidence suggests that cyclin-dependent kinases (CDKs), enzymes that
      normally regulate cell cycle progression, may also participate in the death of
      neurons. This has led to the proposal that CDKs may serve as a therapeutic target
      for neuropathological conditions such as stroke. This brief review will serve to
      examine the evidence supporting the role of CDKs in neuronal death, and will
      evaluate the potential of CDK inhibitors as a neuroprotective strategy for
      ischemic injury.

PMID- 12191605
TI  - Structure-based design of cyclin-dependent kinase inhibitors.
AB  - The eukaryotic cell cycle is tightly regulated by the sequential activation and
      deactivation of the cyclin-dependent kinases (CDKs). Aberrant CDK activity is a
      common defect in human tumours, and clinically, it often confers a poor
      prognosis. The strong genetic link between CDKs and the molecular pathology of
      cancer has provided the rationale for developing small-molecule inhibitors of
      these kinases. X-ray crystallography recently has revealed the molecular details
      of CDK regulation by cyclin binding and phosphorylation, and by complex formation
      with endogenous inhibitors. Knowledge of the structure of CDK2 has been key in
      driving the design and development of a large number of ATP competitive
      inhibitors. Crystallography has revealed that the ATP-binding site of CDK2 can
      accommodate a number of diverse molecular frameworks, exploiting various sites of
      interaction. In addition, residues outside the main ATP-binding cleft have been
      identified that could be targeted to increase specificity and potency. These
      results suggest that it may be possible to design pharmacologically relevant
      ligands that act as specific and potent inhibitors of CDK activity. We provide a
      review of the current state of the field, along with an overview of our current
      inhibitor design studies.

PMID- 12191607
TI  - Designing bisubstrate analog inhibitors for protein kinases.
AB  - Protein kinases play critical roles in signal transduction pathways by
      transmitting extracellular signals across the cell membrane to distant locations
      in the cytoplasm and the nucleus. The development of protein kinase inhibitors
      has been hindered by the broad overlapping substrate specificities exhibited by
      these enzymes. The design of bisubstrate analog inhibitors could provide for the
      enhancement of specificity and potency in protein kinase inhibition. Bisubstrate
      analog inhibitors form a special group of protein kinase inhibitors that mimic
      two natural substrates/ligands and that simultaneously associate with two regions
      of given kinases. Most bisubstrate analogs have been designed to mimic the
      phosphate donor (ATP) and the acceptor components (Ser-, Thr-, or Tyr-containing
      peptides). Recent studies have emphasized the importance of maintaining a
      specific distance between these two components to achieve potent inhibition. In
      this review, we present a discussion of the methods for designing protein kinase
      inhibitors by mechanism-based approaches. Emphasis is given to bivalent
      approaches, with an interpretation of what has been learned from more and less
      successful examples. Future challenges in this area are also highlighted.

PMID- 12191608
TI  - Toward the rational design of protein kinase casein kinase-2 inhibitors.
AB  - Casein kinase-2 (CK2) probably is the most pleiotropic member of the protein
      kinase family, with more than 200 substrates known to date. Unlike the great
      majority of protein kinases, which are tightly regulated enzymes, CK2 is endowed
      with high constitutive activity, a feature that is suspected to underlie its
      oncogenic potential and possible implication in viral infections. This makes CK2
      an attractive target for anti-neoplastic and antiviral drugs. Here, we present an
      overview of our present knowledge about CK2 inhibitors, with special reference to
      the information drawn from two recently solved crystal structures of CK2alpha in
      complex with emodin and with 4,5,6,7-tetrabromo-2-azabenzimidazole (TBB), this
      latter being the most specific CK2 inhibitor known to date. A comparison with a
      series of anthraquinone and xanthenone derivatives highlights the crucial
      relevance of the hydroxyl group at position 3 for inhibition by emodin, and
      discloses the possibility of increasing the inhibitory potency by placing an
      electron withdrawing group at position 5. We also present mutational data
      corroborating the relevance of two hydrophobic residues unique to CK2, Val66 and
      Ile174, for the interactions with emodin and TBB, but not with the flavonoid
      inhibitors quercetin and fisetin. In particular, the CK2alpha mutant V66A
      displays 27- and 11-fold higher IC(50) values with emodin and TBB, respectively,
      as compared with the wild-type, while the IC(50) value with quercetin is
      unchanged. The data presented pave the road toward the rational design of more
      potent and selective inhibitors of CK2 and the generation of CK2 mutants
      refractory to inhibition, useful to probe the implication of CK2 in specific
      cellular functions.

PMID- 12191609
TI  - Designing specific protein kinase inhibitors: insights from computer simulations
      and comparative sequence/structure analysis.
AB  - Protein kinases are important targets for designing therapeutic drugs. We
      describe here a computational approach to extend the usefulness of a single
      protein-inhibitor structure in aiding the design of protein kinase inhibitors.
      This approach is based on using sensitivity analysis to identify the most
      significant functional groups of a lead compound in accounting for binding
      affinity and on using comparative sequence/structure analysis to examine whether
      these functional groups would present specificity. A sensitivity analysis study
      is similar to genetic or chemical modification experiments in which specific
      features of a lead compound are modified to examine whether they affect
      properties such as binding affinity. In this study, the binding affinity was
      estimated by using an implicit-solvent model in which the electrostatic
      contributions were obtained by solving the Poisson equation, and the hydrophobic
      effects were accounted for by using surface-area-dependent terms. The comparative
      sequence/structure analysis involves the study of the amino acid distributions of
      a large number of protein kinases (384 in this study) near the ligand-binding
      sites. This analysis provides useful guiding principles for designing specific
      inhibitors targeted towards a particular kinase. Here, we illustrate the utility
      of these computational approaches by applying them to identify the determinants
      of the recognition between the protein kinase A and two of its inhibitors. One
      inhibitor, balanol, binds to the ATP-binding pocket. The other, protein kinase
      inhibitor, binds to the substrate-binding site. These analyses have helped to
      construct pharmacophore models for mining new drug leads from small-molecule
      libraries and for suggesting how a lead compound or a peptide inhibitor may be
      modified to generate selective inhibitors.

PMID- 12191610
TI  - From consensus sequence to high-affinity ligands: acquisition of signaling
      protein modulators.
AB  - Protein kinases recognize and bind to specific amino acid sequences on their
      protein substrates. These sequences can be readily identified using combinatorial
      peptide libraries. Unfortunately, conventional peptide libraries are not designed
      to identify subtle structural factors that can dramatically enhance enzyme
      affinity since the "local" diversity associated with these libraries is limited
      to the 20 standard amino acids. A parallel synthesis strategy was developed that
      possesses 2 key attributes: moderate size ( approximately 1000 members each), yet
      high structural diversity (50-fold greater than that of conventional peptide
      libraries). Due to their small size, these libraries can be synthesized in
      parallel, which allows each library member to be individually evaluated, and
      eliminates the requirement for subsequent structural deconvolution. Furthermore,
      since these libraries possess a high structural diversity focused within narrow
      spatial windows on the target protein, small regions of the protein can be
      challenged with a multitude of functionality containing structural differences
      that vary from subtle to gross.

PMID- 12191611
TI  - Docking interactions in the mitogen-activated protein kinase cascades.
AB  - Regulation of cellular functions and responses utilizes a number of the signal
      transduction pathways. Each pathway should transduce signals with high efficiency
      and fidelity to avoid unnecessary crosstalks. The mitogen-activated protein
      kinase (MAPK) cascades regulate a wide variety of cellular functions, including
      cell proliferation, differentiation, and stress responses. MAPK is activated by
      MAPK kinase; phosphorylates various targets, including transcription factors and
      MAPK-activated protein kinases; and is inactivated by several phosphatases.
      Recent studies have provided a cue to understand the molecular mechanism
      underlying the signal transduction through the MAPK cascades. In the MAPK
      cascades, docking interactions, which are achieved through a site outside the
      catalytic domain of MAPKs, regulate the efficiency and specificity of the
      enzymatic reactions. The docking interaction is different from a transient enzyme
      substrate interaction through the active center. It has been shown that
      activators, substrates, and inactivators of MAPKs utilize a common site on MAPKs
      in the docking interaction. Then, the docking interaction may regulate not only
      the efficiency and specificity of the cascades, but also the ordered and
      integrated signaling.

PMID- 12191612
TI  - Exploring the mechanisms of vascular smooth muscle tone with highly specific,
      membrane-permeable inhibitors of cyclic GMP-dependent protein kinase Ialpha.
AB  - The structural similarity of cyclic GMP-dependent protein kinase (cGPK) and
      cyclic AMP-dependent protein kinase (cAPK) has made it difficult to study cGPK
      pathways independent of those mediated by cAPK, primarily due to the lack of
      potent and selective cGPK inhibitors. We recently reported a novel peptide
      library screen specifically designed to select for tight-binding peptides that
      identified selective inhibitors of cGPK [Proc Natl Acad Sci USA, 97 (2000)
      14772]. Iterative deconvolution of octameric library arrays on paper identified
      the sequence LRK(5)H (W45). Binding of W45 to cGPK resulted in selective
      inhibition of the kinase, with K(i) values of 0.8 microM and 560 microM for cGPK
      and cAPK, respectively. Cellular internalization of highly charged W45 was
      accomplished by N-terminal fusion of membrane translocation sequences from either
      the human immunodeficiency virus tyrosine aminotransferase protein (47-59) DT-2
      or from the Drosophila Antennapedia homeodomain (43-58) DT-3, respectively. For
      both fusion peptides, DT-2 and DT-3, we observed a potentiating effect with
      respect to the inhibitory potency, with K(i) values 40- to 80-fold lower than
      W45. Fluorescein-labeled DT-2 and DT-3 demonstrated rapid translocation through
      the cytosol and nuclei in a time-dependent manner using cultured cells and intact
      tissue samples (cerebral arteries). The physiological effects of DT-2 and DT-3 as
      selective cGPK inhibitors in smooth muscle were studied in small intact arteries.
      Nitric oxide, a cyclic GMP/cGPK activator, elicited a concentration-dependent
      dilation of isolated rat cerebral arteries, which was markedly inhibited by DT-2
      and DT-3. Collectively, these results indicate that DT-2 and DT-3 effectively
      inhibit nitric oxide-induced vasodilation, further emphasizing the central role
      for cGPK in the modulation of vascular contractility.

PMID- 12191613
TI  - Structure, activity, regulation, and inhibitor discovery for a protein kinase
      associated with apoptosis and neuronal death.
AB  - Death-associated protein kinase (DAPK) is a calmodulin-regulated serine/threonine
      protein kinase associated with neuronal cell death in animal models of disease.
      The recent determination of the 1.5A crystal structure of the catalytic kinase
      domain of DAPK, the discovery of amino acid sequence motifs with sites that are
      preferentially phosphorylated by this kinase, and the development of a
      quantitative enzyme activity assay provide a firm foundation for future studies
      into its regulation, the identification of its physiological substrates, and
      discovery of inhibitors. We summarize the relevant background and ongoing
      investigations that will increase our understanding of the role and regulation of
      this prototype death-associated kinase.

PMID- 12191614
TI  - The novel and specific Rho-kinase inhibitor (S)-(+)-2-methyl-1-[(4-methyl-5
      isoquinoline)sulfonyl]-homopiperazine as a probing molecule for Rho-kinase
      involved pathway.
AB  - We have developed several kinds of protein kinase inhibitors, which are
      classified as isoquinolinesulfonamides and characterized as ATP competitive
      inhibitors of Ser/Thr protein kinases. These include H9, H89, KN62, and 1-(5
      isoquinolinesulfonyl)-homopiperazine (HA-1077) against protein kinase C (PKC),
      protein kinase A, Ca(2+)/calmodulin-dependent protein kinase II, and Rho-kinase,
      respectively, and they have been used widely to confirm the involvement of the
      target protein kinase in biological or physiological reaction(s). In some cases,
      inhibitors have predicted the involvement of the target protein kinase in cell or
      tissue before its precise mechanism or its effector was defined. On a clinical
      level, we developed the Rho-kinase inhibitor HA-1077 as an anti-spastic that
      effectively suppresses the spasm of cerebral arteries after subarachnoid
      hemorrhage. We have improved HA-1077 to obtain (S)-(+)-2-methyl-1-[(4-methyl-5
      isoquinoline)sulfonyl]-homopiperazine (H-1152P), which is a more selective
      inhibitor of Rho-kinase, with a K(i) value of 1.6 nM for Rho-kinase, 630 nM for
      protein kinase A, and 9270 nM for PKC. This inhibitor suppressed the
      phosphorylation of myristoylated alanine-rich C-kinase substance (MARCKS) in
      neuronal cells stimulated with lysophosphatidic acid, whose phosphorylation site
      was confirmed to be the Ser159 residue, using a phosphorylation site-specific
      antibody. In contrast, phorbol 12-myristate 13-acetate-induced phosphorylation of
      MARCKS was scarcely inhibited by H-1152P. Furthermore, lysophosphatidic acid
      stimulated phosphorylation in neuronal cells was characterized as a C3 toxin
      sensitive event. Our results show that the Rho-kinase inhibitor targets a protein
      with a well-known function, MARCKS in neuronal cells. Although MARCKS is widely
      recognized as a substrate of PKC, our results raise the possibility that MARCKS
      is a target protein of Rho-kinase in neuronal cells. In this review, we address
      the possible role of Rho-kinase in neuronal functions, using the Rho-kinase
      specific inhibitor H-1152P.

PMID- 12191615
TI  - Integrin-linked kinase, a promising cancer therapeutic target: biochemical and
      biological properties.
AB  - Integrin-linked kinase (ILK) is an ankyrin repeat-containing Ser/Thr kinase that
      interacts with the cytoplasmic domains of beta(1) and beta(3) integrins. ILK is
      widely expressed in tissues throughout the body, and, as might be expected,
      appears to mediate a diversity of functions relating to its role in coupling
      integrins and growth factor receptors to downstream signaling pathways. Through
      its downstream targets protein kinase B/Akt and glycogen synthase kinase-3beta,
      ILK appears to be involved in several oncogenesis-related events, including
      suppression of apoptosis and promotion of cell survival, as well as cell
      migration and invasion. Over-expression of ILK in epithelial cells results in
      anchorage-independent cell growth with increased cell cycle progression.
      Inoculation of nude mice with ILK over-expressing cells leads to tumor formation.
      Furthermore, increased ILK expression and activity have been correlated with
      malignancy in several human tumor types, including breast, prostate, brain, and
      colon carcinomas. Based on these findings, ILK represents an excellent
      therapeutic target for the prevention of tumor progression. Here, we provide an
      overview of the physical and biochemical properties of ILK, and present data
      describing the impact of small-molecule ILK inhibitors on several ILK-mediated
      cellular functions.

PMID- 12191616
TI  - Inhibition of protein kinase B/Akt. implications for cancer therapy.
AB  - Protein kinase B (PKB, also called Akt) is an important regulator of cell
      proliferation and survival. Amplification of genes encoding PKB isoforms has been
      found in several types of human cancers. In addition, mutations in the
      phosphatase and tensin homolog deleted on chromosome ten (PTEN), one of the most
      frequently mutated tumor suppressor genes, results in elevated PKB activity. PKB
      has a wide range of cellular targets, and the oncogenicity of PKB arises from
      activation of both proliferative and anti-apoptotic signaling. Furthermore, PKB
      contributes to tumor progression by promoting cell invasiveness and angiogenesis.
      These observations establish PKB as an attractive target for cancer therapy. A
      cellular inhibitor of PKB, termed carboxyl-terminal modulator protein, reverts
      the phenotype of viral akt-transformed cells, suggesting that a specific PKB
      inhibitor will be useful in the treatment of tumors with elevated PKB activity.
      Since inhibition of PKB activity induces apoptosis in a range of mammalian cells,
      a PKB inhibitor may be effective, in combination with other anticancer drugs, for
      the treatment of tumors with other mutations.

PMID- 12191617
TI  - Irreversible inhibitors of the erbB family of protein tyrosine kinases.
AB  - The erbB family of transmembrane receptor tyrosine kinases initiates a large
      number of cellular signalling pathways. Their over-expression in human tumours
      correlates with poor prognosis, and they have become important targets for drug
      development. The 4-anilinoquinazolines are potent and selective ATP site
      inhibitors of these enzymes, especially erbB1 (epidermal growth factor receptor).
      Structure-activity studies for binding at the ATP site are narrow, consistent
      with homology and crystal structure-binding models. Combinations of small
      lipophilic groups at the 3'-position of the aniline and electron-donating groups
      at the 6- or 7-positions of the quinazoline result in extremely potent
      (picomolar) reversible inhibitors, several of which are in clinical trial.
      Observation that the erbB family of enzymes contains a unique Cys residue
      (Cys773) close to the ATP-binding site prompted the development of irreversible
      inhibitors, the most successful being 6-acrylamides and related butynamides,
      which show significantly improved in vivo antitumour activity compared with
      closely related reversibly binding compounds. Solubilising side chains can be
      placed either at the terminus of the alkylating unit or at the quinazoline C-7,
      and examples of both types are in clinical trial. Both reversible and
      irreversible inhibitors synergise with a variety of DNA-damaging anticancer
      drugs, and it is likely that the greatest impact of these agents will be in
      combination therapy.

PMID- 12191618
TI  - Inhibition and activation of c-Src: the head and tail of a coin.
AB  - Protein-tyrosine kinases (PTKs) play pivotal roles in many cell systems. The Src
      family kinases (SFKs) are the most characterized PTKs shown to be coupled with
      various cell surface receptors. However, their mode of activation and regulating
      partners are largely unknown. Here we describe a novel mechanism of inhibition
      and activation of c-Src, a representative of the SFKs. Both directions of
      regulation take place at the same site in the catalytic domain of c-Src via a
      peptide- or protein-protein interaction. Our results highlight a novel and
      general mode of kinase regulation that may be applied not only to SFKs, but to
      other PTKs and Ser/Thr kinases as well.

PMID- 12191619
TI  - Establishment of a binding assay for protein kinase C isozymes using synthetic C1
      peptides and development of new medicinal leads with protein kinase C isozyme and
      C1 domain selectivity.
AB  - Conventional and novel protein kinase C (PKC) isozymes contain two cysteine-rich
      C1 domains (C1A and C1B), both of which are candidate phorbol-12, 13-dibutyrate
      (PDBu)-binding sites. We synthesized C1 peptides of 50-70 residues corresponding
      to all PKC isozyme C1 domains using an Fmoc solid-phase strategy. These C1
      peptides were successfully folded by zinc treatment, as monitored by electrospray
      ionization time-of-flight mass spectrometry. We measured the K(d)'s of [3H]PDBu
      for all PKC C1 peptides. Most of the C1 peptides, except for delta-C1A and theta
      C1A, showed strong PDBu binding affinities with K(d)'s in the nanomolar range
      (0.45-7.4 nM) comparable with the respective whole PKC isozymes. The resultant C1
      peptide library can be used to screen for new ligands with PKC isozyme and C1
      domain selectivity. Non-tumor-promoting 1-oleoyl-2-acetyl-sn-glycerol and
      bryostatin 1 showed relatively strong binding to all CIA peptides of novel PKCs
      (delta, epsilon, and eta). In contrast, the tumor promoters (-)-indolactam-V,
      ingenol-3-benzoate, and PDBu bound selectively to all C1B peptides of novel PKCs.
      The preference of tumor promoters for the domain might be related to
      tumorigenesis since recent investigations proposed the involvement of novel PKCs
      in tumor promotion in vivo using transgenic or knockout mice. Moreover, we
      recently have found that a new lactone analogue of benzolactams (6) shows
      significant selectivity in PKCeta-C1B binding.

PMID- 12191620
TI  - Protein kinase inhibitors and antibiotic resistance.
AB  - While antibiotics revolutionized the treatment of infectious disease in the 20th
      century, bacterial resistance now threatens to render many of them ineffective.
      Aminoglycosides are a class of clinically important antibiotics used in the
      treatment of infections caused by Gram-positive and -negative organisms. They are
      bactericidal, targeting the bacterial ribosome, where they bind to the A-site and
      disrupt protein synthesis. Clinical resistance to these drugs occurs mainly via
      enzymatic inactivation by aminoglycoside-modifying enzymes that phosphorylate,
      adenylate, or acetylate the aminoglycoside. Those that phosphorylate (i.e.,
      aminoglycoside kinases) have been shown to be structurally related to eukaryotic
      protein kinases. This was surprising, given the low degree of sequence similarity
      between the groups of enzymes. The nucleotide-binding site, specifically, is very
      similar in structure, suggesting that the two classes of enzymes share a common
      mechanism of phosphoryl transfer. Three strategies can be envisaged for combating
      aminoglycoside kinase-mediated bacterial resistance. The first involves compounds
      that target the antibiotic binding region. Secondly, protein kinase inhibitors
      have been identified that disable aminoglycoside-modifying enzymes by targeting
      the ATP-binding site. Lastly, compounds are being developed that exploit the
      bridged nature of the active site, incorporating nucleotide and substrate motifs.
      A strategy using bifunctional aminoglycoside dimers has also been pursued,
      yielding molecules that bind to the target site on the bacterial ribosome, while
      serving as poor substrates for modifying enzymes. This work holds out the promise
      that effective inhibitors of aminoglycoside-modifying enzymes may eventually
      restore the usefulness of aminoglycoside antibiotics.

PMID- 12191621
TI  - Virulence- and antibiotic resistance-associated two-component signal transduction
      systems of Gram-positive pathogenic bacteria as targets for antimicrobial
      therapy.
AB  - Two-component signal transduction systems are central elements of the virulence
      and antibiotic resistance responses of opportunistic bacterial pathogens. These
      systems allow the bacterium to sense and respond to signals emanating from the
      host environment and to modulate the repertoire of genes expressed to allow
      invasion and growth in the host. The integral role of two-component systems in
      virulence and antibiotic sensitivity, and the existence of essential two
      component systems in several pathogenic bacteria, suggests that these systems may
      be novel targets for antimicrobial intervention. This review discusses the
      potential use of two-component systems as targets for antimicrobial therapy
      against Gram-positive pathogens and the current status in the development of
      inhibitors specific for these systems.

PMID- 12191623
TI  - Proceedings of The Second International Conference on Inhibitors of Protein
      Kinases and Workshop on Computer-aided Drug Design. September 9-15, 2001. Warsaw,
      Poland.

PMID- 12191622
TI  - Modulation of protein kinase signaling by protein phosphatases and inhibitors.
AB  - Protein tyrosine phosphatases (PTPs) form a large family of enzymes that serve as
      key regulatory components in signal transduction pathways. Defective or
      inappropriate regulation of PTP activity leads to aberrant tyrosine
      phosphorylation, which contributes to the development of many human diseases. In
      addition to controlling the phosphorylation states of protein kinase substrates,
      PTPs can also directly modulate protein kinase activity. Evidence suggests that
      PTPs can exert both positive and negative effects on a signaling pathway. Thus,
      further understanding of the fundamental role of protein tyrosine phosphorylation
      in complex and critical signal transduction pathways requires detailed studies of
      both the kinases and the phosphatases. In this review, we first summarize our
      current understanding of PTP structure and function. We then discuss the
      molecular basis of PTP substrate specificity, focusing primarily on mitogen
      activated protein (MAP) kinase phosphatase 3. We demonstrate that the MAP kinase
      phosphatases display exquisite substrate specificity requiring extensive protein
      protein interactions for precise down-regulation of MAP kinase activity. We also
      highlight our recent progress in developing small molecule PTP1B inhibitors.
      Using a novel combinatorial approach that is designed to target both the active
      site and a unique peripheral site in PTP1B, we have obtained a PTP1B inhibitor
      with 2.4 nM affinity and orders of magnitude selectivity against a panel of PTPs.
      Currently, some of the compounds are being evaluated in both cell and animal
      models to further define the role of PTP1B in insulin signaling.

PMID- 12191624
TI  - The CRH1 receptor antagonist R121919 attenuates stress-elicited sleep
      disturbances in rats, particularly in those with high innate anxiety.
AB  - Excessive corticotropin-releasing hormone (CRH) secretion in limbic and
      prefrontal brain areas has been postulated to underly stress-related clinical
      conditions. Studies in mice with deleted or pharmacologically compromised CRH
      type 1 receptors (CRH-R1) point to a key role of the CRH/CRH-R1 signaling cascade
      as a potential drug target. Therefore, we compared the effect of a selective high
      affinity CRH-R1 antagonist (R121919) on sleep-wake behavior in two rat lines
      selectively bred for either high or low innate anxiety. We found that the
      subcutaneous injection of the solvent of R121919, a citrate buffer solution,
      transiently increased circulating levels of the stress hormones ACTH and
      corticosterone and reduced sleep, especially in high-anxiety animals. When
      R121919 was added to the solvent, hormone levels and sleep patterns returned to
      baseline and were indistinguishable between the rat lines. This finding is in
      accord with previous observations from a clinical trial in depressed patients and
      studies in rats with high innate anxiety that suggested major effects of CRH-R1
      antagonism in the presence of a pathological (i.e. CRH hypersecretion) condition
      only.

PMID- 12191625
TI  - Characterization of the longitudinal course of improvement in generalized anxiety
      disorder during long-term treatment with venlafaxine XR.
AB  - OBJECTIVE: To characterize the response to the serotonin and norepinephrine
      reuptake inhibitor, venlafaxine extended release (XR), during the long-term
      treatment of generalized anxiety disorder. METHODS: Data from two double-blind,
      placebo-controlled, 6-month trials of venlafaxine XR for the treatment of
      generalised anxiety disorder were pooled. Criteria for response (> or = 50%
      improvement from baseline HAM-A score) and remission (HAM-A score < or = 7) and
      their temporal profile were used to characterize patient improvement over 6
      months of treatment with venlafaxine XR and placebo. RESULTS: Venlafaxine XR was
      associated with significantly (P<0.001) higher response and remission rates (66
      and 43%, respectively) compared with placebo (39 and 19%), regardless of the
      level of baseline anxiety. In the venlafaxine XR group, 61% of the patients who
      had responded but not remitted by week 8 showed remission by the end of 6 months.
      In comparison, only 39% of placebo responders who did not qualify for remission
      at the end of the first 8 weeks of therapy remitted by the end of the 6 months
      (P=0.007). Relapse occurred in 6% of venlafaxine XR-treated patients and 15% of
      placebo-treated patients (P<0.01). CONCLUSION: This analysis provides further
      insight into the outcome of long-term treatment of generalised anxiety disorder
      with venlafaxine XR and shows for the first time that long-term treatment might
      be necessary to achieve and maintain remission of symptoms.

PMID- 12191626
TI  - Vagus nerve stimulation (VNS) synchronized BOLD fMRI suggests that VNS in
      depressed adults has frequency/dose dependent effects.
AB  - Stimulation of the vagus nerve in the neck can reduce seizures in epilepsy
      patients, and may be helpful in treating depression. PET studies have shown that
      vagus nerve stimulation (VNS) in epilepsy patients causes acute dose (intensity)
      dependent changes in regional cerebral blood flow. We sought to use the newly
      developed VNS synchronized fMRI technique to examine whether VNS BOLD signal
      changes depend on the frequency of stimulation. Six adults with recurrent
      depression were scanned inside a 1.5 T MR scanner. Data were acquired at rest,
      with the VNS device on for 7 s, and also, for comparison, while the patient
      listened to a tone for 7 s. In two separate back-to-back sessions, the VNS
      stimulation frequency was set to either 5 or 20 Hz. Data were transformed into
      Talairach space and then compared by condition. Compared to 5 Hz, 20 Hz VNS
      produced more acute activity changes from rest in regions similar to our initial
      VNS synchronized fMRI feasibility study in depression. Brain regions activated by
      hearing a tone were also greater when VNS was intermittently being applied at 20
      Hz than at 5 Hz. In depressed adults, left cervical VNS causes regional brain
      activity changes that depend on the frequency of stimulation or total dose, or
      both. In addition to the acute immediate effects of VNS on regional brain
      activity, this study suggests further that VNS at different frequencies likely
      has frequency or dose dependent modulatory effects on other brain activities
      (e.g. hearing a tone).

PMID- 12191627
TI  - Early improvement predicts endpoint remission status in sertraline and placebo
      treatments of panic disorder.
AB  - The early identification of likely remitters and non-remitters to pharmacotherapy
      for panic disorder may have important implications for clinical treatment
      decisions. To address this question, combined data from two fixed-dose and two
      flexible dose placebo-controlled studies of sertraline treatment of panic
      disorder were examined. Patients (N=544) diagnosed with panic disorder, with or
      without agoraphobia, were treated with 50 mg of sertraline, 100 mg of sertraline,
      flexible dosages of sertraline, or placebo. Measures of early improvement
      included panic attack frequency (full + limited symptom attacks), anticipatory
      anxiety, the Hamilton Anxiety Rating Scale (HAM-A), and the Clinical Global
      Impression Improvement (CGI-I) Scale. Improvement as reflected in CGI-I ratings
      and change from baseline in the HAM-A at weeks 1, 2, and 3 significantly
      (P<0.0001) predicted endpoint clinical remission (defined at endpoint as no full
      panic attacks and a CGI-Severity rating of 1 or 2). Improvements in panic attack
      frequency and anticipatory anxiety were not consistent predictors in multivariate
      predictive models. Receiver-Operator Curve analyses revealed good specificity
      (0.83) for change in CGI-I at week 2, and good sensitivity (0.82) for change in
      HAM-A at week 3. Predictive success for HAM-A and CGI-I was not significantly
      different for fixed vs. flexible dose sertraline treatment, nor for sertraline
      vs. placebo treatment. The use of ROC analyses for examination of early response
      as a predictor of final remission holds promise for aiding clinicians in decision
      making regarding the need for alternative or supplemental treatment approaches
      during the course of pharmacotherapy for panic disorder.

PMID- 12191628
TI  - Parental depression and depression in offspring: evidence for familial
      characteristics and subtypes?
AB  - The objectives of this paper were twofold. First, to evaluate in a community
      sample the age of onset of major depression in adolescents and young adults with
      and without parental major depression. Second, to examine whether specific
      clinical characteristics of major depression in adolescents and young adults are
      associated with elevated rates of major depression among parents. Baseline and 4
      year follow-up data were used from the Early Developmental Stages of
      Psychopathology Study (EDSP), a prospective-longitudinal community study of
      adolescents and young adults. Results are based on 470 subjects who completed the
      follow-up, for whom diagnostic information for both parents was available, and
      who reported at least one episode of major depression according to DSM-IV
      criteria through second follow-up. Diagnostic assessment in respondents was
      accomplished by using the standardized Munich-Composite International Diagnostic
      Interview (M-CIDI). Information on major depression in parents was collected as
      family history information from the respondents, and additionally from M-CIDI
      diagnostic interviews with parents of the younger cohort. Both recurrence and
      impairment as clinical characteristics of major depression in adolescents and
      young adults were associated with elevated rates of major depression among
      parents. Age of onset as well as overall higher impairment as clinical
      characteristics of major depression in youth were associated with elevated rates
      of parental major depression in the univariate, but not in the multiple,
      analyses. Our findings suggest that clinical features of major depression may
      indicate familial subtypes of the disorder, most evident for recurrence and
      impairment.

PMID- 12191629
TI  - Taxonicity of adolescent melancholia: a categorical or dimensional construct?
AB  - A taxometric analysis was conducted to test the hypothesis that the latent
      structure of melancholia in adolescents is categorical. Two taxometric procedures
      were used: Mean Above Minus Below a Cut (MAMBAC) and Maximum Covariance (MAXCOV)
      analyses. Participants were 378 adolescents presenting for a depression
      evaluation. Indicators of melancholia were constructed using items from the
      Schedule for Affective Disorders and Schizophrenia for School Aged Children (K
      SADS) and the Beck Depression Inventory (BDI). The indicators of melancholia were
      consistent with a categorical latent variable. The findings suggest that the
      latent structure of melancholia in adolescents is similar to its previously
      identified categorical structure in adults. Implications for clinical research
      are discussed.

PMID- 12191630
TI  - Neuropsychological profile in patients with obsessive-compulsive disorder over a
      period of 4-month treatment.
AB  - This study investigated the changes of the neuropsychological functions over a 4
      month period of treatment in patients with obsessive-compulsive disorder (OCD).
      Thirty-nine OCD patients and 31 healthy controls were evaluated with
      neuropsychological and clinical tests. The same tests were readministered 4
      months after pharmacological treatment for the OCD patients. At the first series
      of tests, compared to the controls, the OCD patients were significantly impaired
      on the immediate and delayed recall of Rey-Osterrieth Complex Figure Test (RCFT),
      and on the letter and category of Controlled Oral Word Association Test (COWA).
      They also showed a prolonged response time on Trail Making Test (TMT), part A.
      The severity of OCD measured by Yale-Brown Obsessive-Compulsive Scale (Y-BOCS)
      correlated well with the performance on the immediate and delayed recall of RCFT
      and the response time on TMT, part A. After 4-months' follow-up, the OCD patients
      still showed impairment on the immediate and delayed recall of RCFT and COWA
      category. This is despite the fact that they had improved significantly on these
      functions in comparison with the controls over the period of treatment. In
      addition, an association between OCD symptoms and the performance on the
      neuropsychological tests was not observed. The neuropsychological profile of the
      OCD patients found in the present study is consistent with current theories
      proposing that the frontal-striatal system is the possible pathophysiological
      mechanism underlying the development of OCD.

PMID- 12191631
TI  - Introduction: genetic and epigenetic contributions to tumor evolution.

PMID- 12191632
TI  - Mechanisms underlying epigenetically mediated gene silencing in cancer.
AB  - It has become apparent that epigenetically mediated alterations, which establish
      heritable abnormalities in gene expression, are a fundamental feature of human
      cancer. The best studied of these changes are aberrant gene silencing events
      which involve transcriptional inactivation associated with abnormally methylated
      promoter region CpG islands. A most important aspect of understanding this
      change, which can cause loss of key gene function, concerns dissection of the
      molecular mechanisms that mediate the transcriptional repression and those
      responsible for establishing the abnormal methylation and associated chromatin
      events. This chapter reviews the progress in these arenas.

PMID- 12191633
TI  - Epigenetics wins over genetics: induction of differentiation in tumor cells.
AB  - Malignant cells are genetically abnormal, but can the malignant phenotype revert
      to a non-malignant phenotype without correcting these genetic abnormalities? It
      has been found that this reversion can be achieved by reprogramming tumor cells
      by epigenetic changes induced by differentiation. The epigenetic suppression of
      malignancy by inducing differentiation bypasses the genetic abnormalities in
      tumor cells. Studies with myeloid leukemic cells have shown that some leukemic
      cells can be induced to differentiate by cytokines that control normal
      hematopoiesis, and that myeloid leukemic cells resistant to normal cytokines can
      be induced to differentiate by compounds that use alternative differentiation
      pathways. The epigenetic reprogramming of tumor cells by inducing differentiation
      has also been found with other types of tumors and can be used for tumor therapy.
      By this reversion of the malignant to non-malignant phenotype, epigenetics wins
      over genetics.

PMID- 12191634
TI  - DNA methylation changes in leukaemia.
AB  - Leukaemogenesis is a multi-step process whereby a clonal population arises that
      has undergone successive alterations to the genotype and the phenotype of the
      cells that make up the clone. Leukaemia has traditionally been viewed as a
      genetic disease, however epigenetic defects also play an important role.
      Expression of the DNA methyltransferase enzymes is elevated in leukaemia, and
      aberrant methylation is common with both a decrease in the total genomic 5
      methylcytosine, and a concomitant hypermethylation of CpG island-associated
      tumour suppressor genes. This review will discuss the multitude of DNA
      methylation changes in haematopoietic malignancies and the implications they have
      for diagnosis and treatment.

PMID- 12191635
TI  - BRCA1 methylation: a significant role in tumour development?
AB  - Cancer is a multistep process resulting from an accumulation of genetic mutations
      leading to dysfunction of critical genes, including tumour suppressor genes.
      Epigenetic changes are now also recognised as an important alternative mechanism
      of gene inactivation. In particular, aberrant methylation of the promoter region
      of a gene can lead to silencing ultimately contributing to the initiation or
      malignant progression of tumours. BRCA1, a breast and ovarian cancer
      susceptibility gene, is a tumour suppressor gene involved in the maintenance of
      genome integrity. Recent evidence for BRCA1 hypermethylation corroborates the
      view that this epigenetic alteration may play a determinant role in tumour
      suppressor silencing and possibly tumorigenesis. Here, we offer a summary of the
      data providing evidence for BRCA1 hypermethylation in tumours, and an
      investigation into the associated mechanism leading to BRCA1 silencing. We also
      discuss the impact of BRCA1 hypermethylation, as a form of epigenetic change,
      versus BRCA1 genetic mutations in tumour development.

PMID- 12191636
TI  - Epigenetic versus genetic alterations in the inactivation of E-cadherin.
AB  - Genetic mutation of genes that inhibit the formation of tumours has long been
      known to be one of the main driving forces in the development of cancer.
      Inactivation of one such gene, E-cadherin, is thought to be an important step in
      the development of most, or all, epithelial derived tumour types. Mutations
      within the E-cadherin gene have been identified as the cause of familial gastric
      cancer and loss of expression of E-cadherin has been found to be widespread in
      sporadically occurring epithelial tumours. Despite this, mutations of the E
      cadherin gene have been only rarely found in most types of sporadic cancers.
      However, recent evidence has identified a second mechanism potentially
      responsible for inactivation of E-cadherin, and other important genes, during
      tumourigenesis, namely DNA methylation. This review will examine the importance
      of genetic (mutation) versus epigenetic (DNA methylation) mechanisms in the
      inactivation of E-cadherin during tumour development and also discuss potential
      differences in the functional consequences between inactivation by epigenetic or
      genetic means.

PMID- 12191637
TI  - Role of genetic and epigenetic changes in Burkitt lymphoma.
AB  - All Burkitt lymphomas (BLs) carry reciprocal chromosomal translocations that
      activate the c-myc oncogene through juxtaposition to one of the immunoglobulin
      (Ig) loci. Many BL carry point mutation in the p53 tumor suppressor gene or other
      defects in the p14ARF-MDM2-p53 pathway, and inactivation of the p16INK4a gene by
      promoter methylation or homozygous deletion. This indicates that disruption of
      both the pRb and p53 tumor suppressor pathways is critical for BL development.
      Alterations of other genes, including Bax, p73, and BCL-6, may provide further
      growth stimulation and apoptosis protection. Thus, BL development involves
      multiple genetic and epigenetic changes that drive cell cycle progression and
      avert cell death by apoptosis.

PMID- 12191638
TI  - DNA methylation and genomic imprinting: insights from cancer into epigenetic
      mechanisms.
AB  - Since the discovery of epigenetic alterations in cancer 20 years ago by Feinberg
      and Vogelstein, a variety of such alterations have been found, including global
      hypomethylation, gene hypomethylation and hypermethylation, and loss of
      imprinting (LOI). LOI may precede the development of cancer and may thus serve as
      a common marker for risk, but also as a model for understanding the developmental
      mechanism for normal imprinting.

PMID- 12191639
TI  - The novel BORIS + CTCF gene family is uniquely involved in the epigenetics of
      normal biology and cancer.
AB  - CTCF is a ubiquitous 11 zinc finger (ZF) protein with highly versatile functions:
      in addition to transcriptional silencing or activating in a context-dependent
      fashion, it organizes epigenetically controlled chromatin insulators that
      regulate imprinted genes in soma. Recently, we have identified a CTCF paralogue,
      termed BORIS for Brother of the Regulator of Imprinted Sites, that is expressed
      only in the testis. BORIS has the same exons encoding the 11 ZF domain as
      mammalian CTCF genes, and hence interacts with similar cis elements, but encodes
      amino and carboxy termini distinct from those in CTCF. Normally, CTCF and BORIS
      are expressed in a mutually exclusive pattern that correlates with re-setting of
      methylation marks during male germ cell differentiation. The antagonistic
      features of these two gene siblings are underscored by showing that while CTCF
      overexpression blocks cell proliferation, expression of BORIS in normally BORIS
      negative cells promotes cell growth which can lead to transformation. The
      suggestion that BORIS directs epigenetic reprogramming at CTCF target sites
      impinges on the observations that human BORIS is not only abnormally activated in
      a wide range of human cancers, but also maps to the cancer-associated
      amplification region at 20q13. The sibling rivalry occasioned by aberrant
      expression of BORIS in cancer may interfere with normal functions of CTCF
      including growth suppression, and contribute to epigenetic dysregulation which is
      a common feature in human cancer.

PMID- 12191642
TI  - Stimuli from conspecifics influence brain mast cell population in male rats.
AB  - It is well established that mast cells occur within the brain of many species,
      and that the brain mast cell population is not static, but changes with the
      behavioral and physiological state of the animal. In this study, we tested
      whether exposure to conspecifics alters the number of brain mast cells in male
      rats, and then investigated the nature of stimuli influencing the changes
      observed in the number and localization of brain mast cells. Five days of
      cohabitation with an ovariectomized, estrogen-progesterone (OVX + EP)-treated
      female resulted in the largest number of thalamic mast cells, while pairing with
      such a female physically separated by a wire mesh or with a novel male produced a
      smaller, but significant increase over other pairings (OVX females for 5 days,
      OVX and OVX + EP females for 1 day, familiar or isolated males for 5 days). In
      all groups, mast cells were localized within specific dorsal thalamic nuclei,
      including the paraventricular nucleus, anterior nuclear group, or mediodorsal,
      ventroposterior, or medial geniculate nuclei. The results suggest that the
      behavioral and/or endocrine factors associated with cohabitation with
      conspecifics are sufficient to alter the number of brain mast cell-specific
      nuclei in the thalami of male rats and thus can provide targeted delivery of
      neuromodulators to specific regions of the brain that process information
      concerning the normal physiological state of the animal.

PMID- 12191643
TI  - Short days and exogenous melatonin increase aggression of male Syrian hamsters
      (Mesocricetus auratus).
AB  - Many nontropical rodent species rely on photoperiod as a primary cue to
      coordinate seasonally appropriate changes in physiology and behavior. Among these
      changes, some species of rodents demonstrate increased aggression in short,
      "winter-like" compared with long "summer-like" day lengths. The precise
      neuroendocrine mechanisms mediating changes in aggression, however, remain
      largely unknown. The goal of the present study was to examine the effects of
      photoperiod and exogenous melatonin on resident-intruder aggression in male
      Syrian hamsters (Mesocricetus auratus). In Experiment 1, male Syrian hamsters
      were housed in long (LD 14:10) or short (LD 10:14) days for 10 weeks. In
      Experiment 2, hamsters were housed in long days and half of the animals were
      given daily subcutaneous melatonin injections (15 microg/day in 0.1 ml saline) 2
      h before lights out for 10 consecutive days to simulate a short-day pattern of
      melatonin secretion, while the remaining animals received injections of the
      vehicle alone. Animals in both experiments were then tested using a resident
      intruder model of aggression and the number of attacks, duration of attacks, and
      latency to initial attack were recorded. In Experiment 1, short-day hamsters
      underwent gonadal regression and displayed increased aggression compared with
      long-day animals. In Experiment 2, melatonin treatment also increased aggression
      compared with control hamsters without affecting circulating testosterone.
      Collectively, the results of the present study demonstrate that exposure to short
      days or short day-like patterns of melatonin increase aggression in male Syrian
      hamsters. In addition, these results suggest that photoperiodic changes in
      aggression provide an important, ecologically relevant model with which to study
      the neuroendocrine mechanisms underlying aggression in rodents.

PMID- 12191644
TI  - Hormonal and behavioral responses of starlings during a confrontation with males
      or females at nest boxes during the reproductive season.
AB  - We investigated in an aviary experiment the behavioral and hormonal responses of
      European starlings (Sturnus vulgaris) that were moved from a same sex group to an
      aviary containing either a nest box alone, a nest box and another male, or a nest
      box and a female. Luteinizing hormone (LH) and testosterone (T) levels increased
      significantly and independently of the situation, suggesting that nest boxes were
      the most important stimulus affecting the levels of these hormones. Some birds
      occupied more than two boxes (winners), and others a single or no box (losers).
      Levels of T increased less in males that did not acquire a nest box. However, the
      increase in LH was similar in all males after the test. Singing was positively
      correlated with T levels. Winners started singing earlier and sang more during a
      contest than losers. In the presence of females LH increased more in winners than
      in losers, while the increase in T was similar in both groups. In females, there
      was no increase in T but LH increased in the presence of males. Levels were
      higher in females paired with winners than in females paired with losers.
      Finally, winners advertised their nest boxes more frequently than losers. These
      results indicate that within a relatively short time frame levels of LH and T
      increase following the transfer from a flock to a territorial situation and can
      react independently from each other depending on reproductive circumstances. For
      males, the possession of a nest box and, for females, the qualities of the male
      seemed to be the most important factors stimulating reproduction.

PMID- 12191645
TI  - Autonomic and glucocorticoid associations with the steady-state expression of
      latent Epstein-Barr virus.
AB  - Previous studies have demonstrated the impact of psychological stress on the
      steady-state expression/reactivation of latent Epstein-Barr virus (EBV). Stress
      induced decrements in the cellular immune response result in less control over
      the expression of the latent virus, resulting in increases in antibody to the
      virus. In Study 1, we investigated whether the steady-state expression of latent
      EBV in vivo differed between high and low stress reactors, as defined by
      sympathetic cardiac reactivity. Autonomic activity and antibody titers to Epstein
      Barr virus capsid antigen (VCA) were measured in 50 elderly women latently
      infected with EBV. Results revealed that women who were high stress reactors were
      characterized by higher antibody titers to the latent virus than low stress
      reactors. High reactors tended to show larger stress-related increases in
      cortisol than low reactors, but the differences were not significant. Daily
      stressors can activate the autonomic nervous system and promote the release of
      pituitary and adrenal hormones, especially in high reactors. Glucocorticoid
      hormones have been shown to reactivate EBV in vitro from cells latently infected
      with the virus. We hypothesized that absolute levels of plasma cortisol may not
      be the only explanation for stress-induced reactivation of latent EBV and that
      the diurnal changes in the production of cortisol may be an important factor in
      these interactions. To examine the feasibility of this hypothesis, an in vitro
      study was conducted (Study 2) to determine whether changing glucocorticoid
      concentrations in the medium, in which EBV latently infected cells were cultured,
      to mimic diurnal changes in plasma cortisol concentrations would enhance the
      reactivation of the latent virus. Cells latently infected with EBV were exposed
      to either constant or varying concentrations of the synthetic glucocorticoid
      hormone dexamethasone (Dex), for 72 h. Results revealed a three- to eightfold
      enhancement of reactivation of latent EBV in cells pulsed with varying Dex
      concentrations when compared with cells exposed to a constant and/or a higher
      mean level of one Dex concentration. Together, these studies raise the
      possibility that differences in the kinetics of glucocorticoid concentrations may
      contribute to differences in the reactivation of latent EBV.

PMID- 12191646
TI  - Presence of mother and unfamiliar female alters levels of testosterone,
      progesterone, cortisol, adrenocorticotropin, and behavior in maturing Guinea
      pigs.
AB  - Although the guinea pig is characterized by precocial physical development and
      minimal active maternal care, studies suggest the presence of the mother can
      influence neuroendocrine and behavioral activity of offspring even well beyond
      weaning. Previous results may have been influenced by the procedure of housing
      weaned subjects with the mother to within 2 days of testing. The present study
      examined approximately 40-day-old guinea pigs housed apart from the mother for 0
      (not rehoused), 2, or 10 days. Rehousing without the mother led to elevations in
      plasma testosterone (measured in males), progesterone (measured in females),
      cortisol, and adrenocorticotropin (ACTH) (both measured in males and females).
      Offspring housed without the mother for 10 days had the highest progesterone,
      cortisol, and ACTH levels. Testosterone elevations were observed in 2-day-, but
      not 10-day-, rehoused animals. Regardless of rehousing condition, 60 min
      isolation in a novel test cage elevated progesterone, cortisol, and ACTH, and
      reduced testosterone. These effects were all moderated if the subject was tested
      with the mother or another female. Sexual behavior toward the mother was observed
      frequently, but only in males housed apart from her prior to testing. Overall,
      males and females that had been housed apart from the mother interacted with her
      as they would an unfamiliar female. Our results corroborate previous findings,
      suggest the effect of housing apart from the mother on male testosterone is
      transitory, and indicate that continuous housing with the mother past weaning
      suppresses circulating progesterone in females and cortisol and ACTH in both
      sexes.

PMID- 12191647
TI  - Effects of cortisol on aggression and locomotor activity in rainbow trout.
AB  - Noninvasive administration of cortisol through the diet resulted in relatively
      rapid (<1.5 h) and highly reproducible increases in plasma cortisol in rainbow
      trout, comparable to changes seen in fish subjected to substantial stress.
      Juvenile rainbow trout were reared in isolation for 1 week, before their daily
      food ration was replaced by a meal of cortisol-treated food corresponding to 6 mg
      cortisol kg(-1). All fish were observed for 30 min, beginning at 1 or 48 h
      following the introduction of cortisol-treated food. Additional cortisol (75% of
      the original dose on Day 2, and 50% on Day 3) was administered to the long-term
      cortisol-treated group. The resulting blood plasma concentrations of cortisol
      were similar in short- and long-term treated fish, and corresponded to those
      previously seen in stressed rainbow trout. Controls were fed similar food without
      cortisol. Half of the fish from each treatment group (controls and short- and
      long-term cortisol) were subjected to an intruder test (a smaller conspecific
      introduced into the aquarium), while half of the fish were observed in isolation.
      In fish challenged by a conspecific intruder, short-term cortisol treatment
      stimulated locomotor activity, while long-term treatment inhibited locomotion.
      Aggressive behavior was also inhibited by long-term cortisol treatment, but not
      by short-term exposure to cortisol. Cortisol treatment had no effect on locomotor
      activity in undisturbed fish, indicating that the behavioral effects of cortisol
      were mediated through interaction with other signal systems activated during the
      simulated territorial intrusion test. This study demonstrates for the first time
      that cortisol has time- and context-dependent effects on behavior in teleost
      fish.

PMID- 12191648
TI  - Gender differences in the validity of testosterone measured in saliva by
      immunoassay.
AB  - We rigorously evaluated gender differences in the measurement validity of
      salivary testosterone. Matched serum, saliva, and finger stick blood spot
      specimens were collected from 40 (20 males) young adults (aged 18-27 years).
      Saliva was assayed for testosterone by two independent (isotopic and non
      isotopic) immunoassay methods. Serum was assayed by commercially available
      immunoassay kits for free and total testosterone. An immunoassay was developed
      for the measurement of testosterone in dried blood spots and is presented in
      detail so as to be reproducible from this report. Regardless of assay method,
      salivary testosterone levels are modestly correlated with serum levels for males
      but not necessarily for females. Blood spot assay results were highly correlated
      with serum total and free testosterone for both males and females. Substitution
      of saliva assay results for serum values substantially underestimates known
      testosterone-behavior associations, and this effect is much more pronounced for
      females than for males. The findings have important implications for the use and
      potential misuse of noninvasive measures of testosterone, and with respect to
      statistical power, the probability of observing significant testosterone-behavior
      relationships.

PMID- 12191649
TI  - Asynchrony in the estrous cycles of golden hamsters (Mesocricetus auratus).
AB  - The golden hamster has been described as exhibiting estrous cycle synchrony
      caused by social dominance. This has recently been reexamined by J. C. Schank
      (2000, Horm. Behav. 38, 94-101) with the aid of computer simulations. He
      concluded that there is no evidence for cycle synchrony among golden hamsters. In
      the present article we confirm this theoretical approach with the help of long
      term experiments. Indeed, estrous cycle asynchrony was observed. Singly housed
      female golden hamsters in phase with their neighbors and in physical contact
      desynchronized their 4-day cycles after 2 or 3 weeks. Asynchrony was caused
      mainly by stochastic 5-day cycles. Statistical analysis was performed using a
      Monte-Carlo bootstrap approach. Based on the empirical data, an individual-based
      computer model was developed to simulate the dynamics of cycle desynchronization.
      Potential advantages were deduced for the population level. It emerged that
      estrous cycle asynchrony led to higher reproductive success for females where the
      probability of fertilization was low (e.g., after hibernation, poor habitat).

PMID- 12191650
TI  - The effects of serotonin agonists on the hypothalamic regulation of sexual
      receptivity in Syrian hamsters.
AB  - One brain region that has been implicated in the regulation of lordosis is the
      medial preoptic-anterior hypothalamic continuum (MPOA-AH). Previous studies have
      suggested that this zone may be part of the circuit mediating the effects of
      serotonin (5-HT) on sexual receptivity. In the present experiments, we
      investigated the role of 5-HT(1a/7) and 5-HT(2) receptor subtypes in the MPOA-AH
      in the control of lordosis. In two experiments, either 5-HT(1a/7) or 5-HT(2)
      agonists were injected unilaterally into the MPOA-AH of ovariectomized,
      hormonally primed female hamsters. In the first experiment, microinjections of
      the 5-HT(1a/7) agonist 8-hydroxy-2,9-(di-n-propylamino)tetralin resulted in an
      attenuation of the lordosis posture by causing a decrease in the mean lordosis
      duration and an increase in the number of lordosis episodes over the entire
      testing period. In the second experiment, microinjections of the 5-HT(2b/2c)
      agonist m-chlorophenylpiperazine did not result in any changes in sexual
      receptivity. However, microinjections of the 5-HT(2) agonist (2,5-dimethoxy-4
      iodophenyl)-2-aminopropane HCl facilitated lordosis by increasing the mean
      lordosis duration and decreasing the number of lordosis episodes in the first 5
      min of the testing period. These data indicate that serotonin may act in the MPOA
      AH via 5-HT(1a/7) receptors to attenuate and 5-HT(2) receptors to facilitate
      sexual receptivity.

PMID- 12191651
TI  - Endocrine correlates of rank, reproduction, and female-directed aggression in
      male Japanese macaques (Macaca fuscata).
AB  - Fecal testosterone and cortisol levels in six wild male Japanese macaques (Macaca
      fuscata), three of high rank and three of low, were analyzed to investigate the
      hormonal correlates of rank, reproduction, and female-directed aggression. The
      study encompassed the 6-month mating season, from October 1999 to March 2000,
      during which time 251 fecal samples and approximately 550 h of behavioral data
      were collected. Dominant males were not found to differ from subordinate males in
      overall rates of aggressive or copulatory behavior. Likewise, testosterone
      excretion, which peaked in the early part of the mating season and declined
      gradually thereafter, did not differ significantly by rank. High-ranking males,
      however, were observed to excrete significantly higher levels of cortisol than
      low-ranking males, suggesting that dominance may carry costs. The two hormones
      were found to be inversely correlated in the two most dominant males, but
      independent in all others. Rate of noncontact aggression was significantly
      correlated with testosterone, while no significant relationships were observed
      between testosterone and contact aggression nor any aspect of copulatory
      behavior. These data further support the contention that social subordinance and
      stress are not inexorably linked, as well as suggest that elevated glucocorticoid
      concentrations in high-ranking males may reflect increased metabolic costs
      associated with dominant male reproductive strategy.

PMID- 12191652
TI  - Characterization of a gene which encodes a mannosyltransferase homolog of
      Paracoccidioides brasiliensis.
AB  - We screened an expression library of the yeast form of Paracoccidioides
      brasiliensis with a pool of human sera that was pre-adsorbed with mycelium, from
      patients with paracoccidioidomycosis (PCM). A sequence (PbYmnt) was obtained and
      characterized. A genomic clone was obtained by PCR of P. brasiliensis total DNA.
      The sequence contained a single open reading frame (ORF) encoding a protein of
      357 amino acid residues, with a molecular mass of 39.78 kDa. The deduced amino
      acid sequence exhibited identity to mannosyl- and glycosyltransferases from
      several sources. A DXD motif was present in the translated gene and this sequence
      is characteristic of the glycosyltransferases. Hydropathy analysis revealed a
      single transmembrane region near the amino terminus of the molecule that
      suggested a type II membrane protein. The PbYmnt was expressed preferentially in
      the yeast parasitic phase. The accession number of the nucleotide sequence of
      PbYmnt and its flanking regions is AF374353. A recombinant protein was generated
      in Escherichia coli. Our data suggest that PbYmnt encodes one member of a
      glycosyltransferase family of proteins and that our strategy was useful in the
      isolation of differentially expressed genes.

PMID- 12191653
TI  - Large-scale preparation of biologically active measles virus haemagglutinin
      expressed by attenuated vaccinia virus vectors.
AB  - A procedure described here allows the efficient and rapid purification of
      histidine-tagged measles virus haemagglutinin that is synthesized under the
      control of powerful promoters (PSFJ1-10 and PSFJ2-16) of the highly attenuated
      vaccinia virus (VV) strain LC16mO. A single affinity chromatography step purifies
      recombinant haemagglutinin proteins from the lysates of cells infected with the
      recombinant VVs. The recovery and purity are both very high (a yield of 0.5-2.8
      mg/10(8) cells and purity of >94-98%), indicating that this procedure is
      approximately 400 times more efficient than the conventional methods used to
      prepare haemagglutinin. The haemagglutinins are correctly transported to the cell
      surface and have haemadsorption activity. Moreover, the recombinant
      haemagglutinin proteins cooperate with the measles virus fusion protein to elicit
      cell fusion activity. In addition, the antibody titres against measles virus, as
      measured by enzyme-linked immunosorbent assay using the purified haemagglutinin
      as the capture antigen, correlated closely with neutralization test titres (R(2)
      = 0.84, p < 0.05), indicating the preservation of immunologically relevant
      antigenicity. Such recombinant haemagglutinin preparations will be useful in
      diagnostic tests that measure functional anti-measles immunity and investigate
      the biological functions and structure of the haemagglutinin.

PMID- 12191654
TI  - Introduction. Cryptosporidiosis: current trends and challenges.

PMID- 12191655
TI  - Cryptosporidiosis: biology, pathogenesis and disease.
AB  - Ninety-five years after discovery and after more than two decades of intense
      investigations, cryptosporidiosis, in many ways, remains enigmatic.
      Cryptosporidium infects all four classes of vertebrates and most likely all
      mammalian species. The speciation of the genus continues to be a challenge to
      taxonomists, compounded by many factors, including current technical difficulties
      and the apparent lack of host specificity by most, but not all, isolates and
      species.

PMID- 12191656
TI  - Cryptosporidiosis: epidemiology and impact.
AB  - Cryptosporidium was first recognized in humans in 1976 and came to prominence in
      the 1980s and 1990s as a cause of severe diarrheal illness in patients with AIDS.
      Its hardy, chlorine-resistant oocysts, tiny size, low infectious dose, fully
      infectious development when shed and zoonotic potential make it a threat in
      drinking and recreational water, contaminated food, day care centers, hospitals,
      and in persons with exposure to animals or unsanitary conditions, with
      potentially huge, long-term impact in malnourished children, as reviewed herein.

PMID- 12191657
TI  - Recent advances in cryptosporidiosis: the immune response.
AB  - An increased understanding of host immune responses to Cryptosporidium parvum
      which are responsible for clearance of primary infection and resistance to
      reinfection, and characterization of the parasite molecules to which they are
      directed, are essential for discovery of effective active and passive
      immunization strategies against cryptosporidiosis. In this article, recent
      advances in knowledge of humoral and cellular immune responses to C. parvum,
      their antigen specificities, and mechanisms of protection are briefly reviewed.

PMID- 12191658
TI  - Genomics and genetics of Cryptosporidium parvum: the key to understanding
      cryptosporidiosis.
AB  - This paper focuses on recent advances in the genetics and genomics of
      Cryptosporidium parvum. The approach to and the relevance of sequencing the
      genomes of C. parvum type 1 and type 2 are discussed, as well as new insights
      into the genetic heterogeneity of this species.

PMID- 12191659
TI  - Antiviral memory T-cell responses in the lung.
AB  - Recent studies have identified distinct populations of memory T cells that
      persist in the lungs following respiratory virus infections, and contribute to
      the control of secondary virus infections. Here we discuss the establishment,
      maintenance and recall of memory T cells in the lung.

PMID- 12191660
TI  - Aspects of the persistence of foot-and-mouth disease virus in animals--the
      carrier problem.
AB  - Foot-and-mouth disease virus (FMDV) is a member of the Aphthovirus genus in the
      Picornaviridae family. Seven distinct serotypes, each including a wide range of
      variants, have been defined. FMD, affects wild and domesticated ruminants and
      pigs, is difficult to control and is the major constraint to international trade
      in livestock and animal products. After the acute stage of infection, FMDV may
      cause a prolonged, asymptomatic but persistent infection in ruminants. Also,
      vaccinated or naturally immune animals subsequently exposed to live virus may
      become persistently infected (the so-called carriers), a situation which can
      result in export embargoes if vaccination is included in a country's control
      policy.

PMID- 12191661
TI  - An SEM evaluation of several adhesive systems used for bonding fiber posts under
      clinical conditions.
AB  - OBJECTIVES: The objective of this investigation was to evaluate the effectiveness
      of three 'one-bottle' and two 'three step' adhesive systems (as controls) in the
      formation of resin tags, adhesive lateral branches and a resin dentin
      interdiffusion zone (RDIZ) when used to bond fiber posts under clinical
      conditions. This study was performed using standardized SEM observations and
      scoring resin tag formation and density. METHODS: Fifty root canal treated teeth,
      already scheduled for extraction for endodontic or periodontal reasons, were
      selected for this study. The patients were informed and their written consent was
      obtained. The samples were randomly allocated to five groups of ten samples each.
      Group 1: All Bond 2 with C & B (Bisco); Group 2: Scotchbond Multipurpose Plus
      with Opal Luting Composite (3M); Group 3: Scotchbond 1 in combination with Rely X
      ARC resin cement (3M); Group 4: One-step with C & B resin cement (Bisco); Group
      5: All Bond Experimental with Post Cement HI-X (Bisco). The adhesive systems and
      resin cements were used strictly according to the manufacturers' instructions.
      The priming-adhesive solution of each 'one-bottle' system was light-cured before
      placing the resin cement and the post. Fifty Aestheti-Plus posts (white quartz
      fiber posts, RTD, France) were used. A week later, the roots were extracted and
      processed for SEM observations. RESULTS: All the adhesive systems showed a RDIZ
      and resin tag and adhesive lateral branch formation. Microscopic examination of
      the restored interfaces of Groups 1 and 2 showed a higher percent of RDIZ than
      those found in samples of Groups 3, 4 and 5. RDIZ morphology was easily
      detectable and uniform in the first two thirds of the root canals, whilst in the
      apical third the RDIZ was not uniformly present. Resin tag morphology and
      formation were significantly more detectable in the cervical and middle areas
      than in the apical zone. No statistically significant differences were found
      among the five groups coronally, while in the apical and middle thirds two 'one
      bottle' systems (Groups 3 and 4) showed significantly less resin tags than the
      control Groups 1, 2 and the experimental Group 5. No statistically significant
      differences were found among the three 'one-bottle' systems in the three
      evaluated areas. The standardization of SEM observations and scoring resin tag
      formation allowed statistical evaluation. CONCLUSIONS: The 'three step' adhesive
      systems can create a wider micromechanical interlocking between adhesive
      materials and etched dentin than 'one-step' systems.

PMID- 12191662
TI  - Influence of drying and HEMA treatment on dentin wettability.
AB  - OBJECTIVES: The aim of this study was to evaluate the effect of drying time and
      primer pre-application (35% HEMA in water) on water spreading/infiltration on
      dentin. METHODS: Freshly extracted molars were embedded in resin and sectioned on
      their coronal side. Flat occlusal dentin surfaces were prepared using wet SiC
      paper from nos. 80-4000. A computerized contact angle device complementing a
      special software (Wingoutt) was used to measure the contact angle (theta)
      kinetics of a reference liquid (pure H(2)O) in the ten groups each of ten dentin
      surfaces during 120 s: Gp1: etched (37% phosphoric acid for 15 s) and blot-dried;
      Gp2: 3 s dried; Gp3: 5 s air-dried; Gp4: 10 s air-dried; Gp5: 20 s air-dried;
      Gp6: 30 s air-dried; Gp7: 1 min dried with hair dryer; Gp8: 5 s air-dried and
      HEMA treated; Gp9: 30 s air-dried followed by HEMA treatment; Gp10: HEMA treated
      prior to 30 s air-drying. three drops were applied on each sample. 40 contact
      angles were recorded for each drop with a frequency of one measure every 3 s. A
      one-way ANOVA test was used for data analysis. A PLSD test was conducted to
      identify statistical differences between pairs of groups at a reliability level
      of 95%. RESULTS: At each measurement time, air-drying, whatever its duration,
      significantly decreased the wetting ability of the pure water on the etched
      dentin in comparison with the blot-dried group. The contact angle increases with
      drying time. No significant differences in water contact angle were obtained
      between 3, 5 and 10 s in spite of a slight decrease in the spreading/infiltration
      ability of water the longer the drying time. HEMA increases the
      spreading/infiltration ability of water on 5 or 30 s air-dried etched dentin
      surfaces; 30 s air-drying did not alter the spreading/infiltration ability of the
      water on etched and HEMA treated dentin. SIGNIFICANCE: Dentin hydrophobicity
      increases depending on air-drying time. HEMA-based primer allows to prevent
      collagen collapse, which may be created by air-drying and partly rewet the
      collapsed collagen network.

PMID- 12191664
TI  - Dentin shear strength: effect of distance from the pulp.
AB  - OBJECTIVE: Dentin structure varies with orientation and location. Ultimate shear
      strength (USS) has also been found in previous studies to vary with location. The
      present study further explores this relationship between USS and various
      locations in coronal dentin as well as distance from the pulp. METHODS: Stick
      specimens were prepared from coronal dentin located in the center or under cusps
      of human molar teeth. These were tested in the shear mode at various distances
      from the pulp. RESULTS: Median values ranged from 52.7 (range 29.0-73.1) MPa near
      the pulp to 76.7 (range 53.9-104.0) MPa near the dentino-enamel junction. No
      differences were found among the buccal, central or lingual locations, however,
      the USS near the pulp was found to be significantly lower. SIGNIFICANCE: The
      properties of coronal dentin vary with distance from the pulp, which may affect
      adhesion and other aspects of restorative dentistry.

PMID- 12191665
TI  - Polymerization shrinkage-strain and microleakage in dentin-bordered cavities of
      chemically and light-cured restorative materials.
AB  - OBJECTIVES: The aim of this study was to evaluate in vitro the relationship
      between polymerization shrinkage and microleakage in dentin-bordered
      restorations. METHODS: Four light-cured restorative materials in combination with
      their respective dental bonding agents (DBA) were investigated: Tetric
      Ceram/Syntac classic (Vivadent), Solitaire/Gluma Solid bond (Heraeus Kulzer),
      Definite/Etch & Prime 3.0 (Degussa), Solitaire 2/Gluma Solid bond (Heraeus
      Kulzer). The chemically cured resin Degufill sc microhybrid (Degussa) in
      combination with ART Bond (Coltene) was also included. Polymerization shrinkage
      of the restorative materials was measured using three different methods
      (dilatometer, linometer, buoyancy method) and analyzed with ANOVA. For the
      determination of microleakage, caries-free human molars were embedded in acrylic
      resin and subsequently abraded with a wet abrasion machine to produce four level
      dentin surfaces. One hundred sixty cavities (3 mm diameter/1.5 mm deep) were
      randomly assigned to four groups of equal size. The groups were restored without
      (group 1 and 2) and with DBA (group 3 and 4), and either not subjected (group 1
      and 3) or subjected (group 2 and 4) to 2000 cycles from 5-55 degrees C. Each
      group was further divided into five material subgroups of eight cavities each.
      Microleakage was determined using a dye penetration test assessed at depths of
      200, 400 and 600 microm into the fillings. Data were analyzed with the Kruskal
      Wallis and the Mann-Whitney test. RESULTS: All three methods of measuring
      polymerization shrinkage (PS) generated the same, statistically secured ranking
      for the four light-cured restorative materials: PS Definite < PS Tetric Ceram <
      PS Solitaire 2 < PS Solitaire. In the microleakage study, only a few
      statistically significant differences were observed. Etch & Prime 3.0/Definite in
      group 3 and Solid Bond/Solitaire 2 in group 4 tended to exhibit the least
      microleakage. Correlation coefficients between aggregated shrinkage and
      microleakage data were 0.3 for group 3 and -0.2 for group 4. SIGNIFICANCE: The
      results do not suggest any correlation between polymerization shrinkage and
      microleakage in dentin of direct adhesive restorations.

PMID- 12191663
TI  - Titanium casting into phosphate bonded investment with zirconite.
AB  - OBJECTIVE: Reaction layer structure of the titanium castings surface was
      investigated when a new centrifuge-vacuum-pressure cast titanium machine and a
      zirconite inner investment was used. METHODS: The micro-hardness of titanium
      castings was measured using a Knoop's hardness tester. The structure of reaction
      layers and the distribution of elements on the surfaces of titanium castings were
      analysed by SEM and EDS, respectively, when zirconite was used as the inner
      investment for cast titanium. RESULTS: Knoop's micro-hardness at distances of 50
      and 75 microm from the titanium casting surfaces made directly in phosphate
      investment molds had significantly harder surfaces than those made in zirconite
      coating molds. The thickness of the reaction layer on the surface of titanium
      castings was <35 microm with zirconite coating and was >50 microm without
      zirconite coating. The structure of reaction layer was divided into four layers
      from the outer surface to the inner including: sintering layer, alpha-Case, Si
      rich layer, acicular crystal structure. The distribution of elements was
      different on each layer. SIGNIFICANCE: The thickness of the cast titanium
      reaction layer was reduced when the wax patterns were coated with zirconite. The
      surface of the titanium castings was smooth and without cracks, and the
      investment on the surface of titanium castings was easily removed.

PMID- 12191666
TI  - Characterization of sound human dentin particles of sub-millimeter size.
AB  - OBJECTIVES: To obtain small dentin particles to provide material for the
      characterization of dentin. To study the interaction of etchants with dentin not
      covered by a smear layer and bonding agents. METHODS: Sound human dentin
      particles of sub-millimeter sizes were obtained by room temperature high-pressure
      fragmentation. Smear-layer free particles of three different average sizes were
      obtained by sieving. Surface areas were measured by the BET method. Simultaneous
      thermogravimetric and differential thermal analysis was carried out on all
      specimens and etched samples. Densities were measured by helium pycnometry.
      RESULTS: On average, the water, organic and mineral contents show the expected
      proportions. The more dense particles tend to be in the smaller sized fractions.
      Thus dentin particles of average size 100 microm have a density of 2.482(0.002)
      g/ml which is statistically different from the 300 microm average sized particles
      with 2.306(0.002) g/ml. However, the respective measured specific surface areas
      of 2.54(0.01) and 2.50(0.02) m(2)/g are not found to be statistically different.
      The specific surface areas of dentin particles increase upon etching, the
      increase being related to acid strength. Thermal analysis of acid-etched 200
      microm diameter particles shows up to 75% loss of carbonate and only 30% loss of
      phosphate. SIGNIFICANCE: Smear-layer free dentin particles which have not been
      exposed to heat by grinding can be obtained by room temperature high-pressure
      fragmentation. Such sub-millimeter sized dentin particles can be acid-etched to
      significantly increase their specific surface area. Thermogravimetry used to
      analyze carbonate and phosphate contents gives new insight to the buffering
      action of human dentin.

PMID- 12191667
TI  - Effect of surface conditioning and restorative material on the shear bond
      strength and resin-dentin interface of a new one-bottle nanofilled adhesive.
AB  - OBJECTIVES: To determine the effect of different combinations of surface
      conditioning (DeTrey Conditioner 36, NRC, no etching) and restorative materials
      (Dyract AP, Spectrum TPH) on the shear bond strength of Prime and Bond NT to
      enamel and dentin, and to characterize the resin-dentin interface produced by
      these combinations. METHODS: Shear bond strength was tested on 30 enamel and 30
      dentin flat labial surfaces of extracted bovine teeth. The enamel and dentin
      specimens were randomly assigned to six groups of five teeth each and treated
      using different combinations of surface conditioners and restorative materials
      with Prime and Bond NT. Scanning electron microscope (SEM) observation of argon
      ion-etched specimens was done to evaluate the resin-dentin interface. RESULTS:
      The type of surface conditioning and restorative material had significant effects
      on dentin bond strengths. Etching the dentin prior to application of Prime and
      Bond NT significantly increased bond strength and caused formation of a hybrid
      layer for Spectrum TPH. For Dyract AP, dentin etching generally did not improve
      bond strength despite the formation of a hybrid layer. On enamel, Prime and Bond
      NT had consistently high bond strengths on etched specimens. SIGNIFICANCE: The
      results showed that Dyract AP and Spectrum TPH, when used with Prime and Bond NT
      have different bonding mechanisms and the effect of surface conditioning on their
      shear bond strength differs. Clinicians should be aware of these effects in order
      to optimize bonding.

PMID- 12191668
TI  - Response of human pulps following acid conditioning and application of a bonding
      agent in deep cavities.
AB  - OBJECTIVES: The aim of this in vivo study was to evaluate the human dental pulp
      response when a one-bottle adhesive system was applied on etched or unetched deep
      dentine. METHODS: Eighteen class V deep cavity preparations were divided in three
      groups: group 1-total etching + two coats of single bond (SB) + composite resin
      (Z-100); group 2-enamel etching + two coats of SB + Z-100; group 3-cavity floor
      lined with a calcium hydroxide liner (Dycal) + acid-etching of enamel and lateral
      walls + two coats of SB + Z-100. Two teeth were used as intact control group.
      After 30 days the teeth were extracted and processed through H and E, Masson's
      trichrome and Brown and Brenn staining techniques. RESULTS: Moderate inflammatory
      response, disorganization of pulp tissue, as well as, deposition of thin layer of
      reactionary dentin were observed in group 1 teeth in which the remaining dentin
      thickness (RDT) was less than 300 microm. These histological findings appear to
      be related to long resin tags formation and bonding agent diffusion through
      dentinal tubules. In group 2, slight inflammatory response was observed only in
      one tooth in which the RDT was 162 microm. In group 3, all the teeth showed
      normal histological characteristics which were similar to the intact control
      group. Presence of bacteria was not correlated with the intensity of pulpal
      response. The patients reported no symptoms during the experiment. Radiographic
      evaluation showed no periapical pathology for any of the teeth. SIGNIFICANCE AND
      CONCLUSIONS: Acid-etched deep dentin (RDT less than 300 microm) lined with SB
      causes more intense pulpal response than unetched deep dentin. Based on the
      results observed in the present study and the conditions in which it was carried
      out, we recommend the application of a biocompatible liner before etching deep
      dentin and applying SB.

PMID- 12191669
TI  - Relationship between the strength of glass ionomers and their adhesive strength
      to metals.
AB  - OBJECTIVES: The objective of this study was to examine the possible correlation
      between the strength of glass ionomers and their adhesive strength to metals.
      METHODS: Three different brands of glass ionomers mixed at four different P/L
      ratios were evaluated. The compressive and diametral tensile strengths of the
      cements were determined. The shear bond strengths were determined between four
      different types of dental casting alloys and the cement made with the different
      P/L ratios. RESULTS: Significant (p < 0.05) increases in the bond strength to any
      of the metal surfaces were found in the cement specimens mixed at the highest P/L
      ratio compared to those mixed at the lowest P/L ratio. For two glass ionomers (FI
      and DNT), the specimens prepared at the highest P/L ratio showed significantly
      greater diametral tensile strength than those prepared at the lowest P/L ratio (p
      < 0.05). SIGNIFICANCE: The present study showed a significant correlation between
      diametral tensile strengths and bond strengths. It is suggested that the use of
      glass ionomers with high mechanical strength is an important factor of enhancing
      the adhesion to metal surfaces.

PMID- 12191670
TI  - A note on the temperature dependence of the flexural strength of a porcelain.
AB  - OBJECTIVES: The purpose of this study is to determine the temperature dependence
      of the flexural strength of a dental porcelain (IPS-Classic Dentin; manufacturer:
      Ivoclar, Liechtenstein) with temperature between its glass transition (T(g) =
      581.7 degrees C) and room temperature. METHODS: The flexural strength was
      measured in three-point bending tests on an Instron 4204 testing apparatus. The
      strength values were determined for the temperatures T = 20, 300, 400, 450, 500,
      550, and 600 degrees C. RESULTS: In the temperature interval 20 < or = T < or =
      400 degrees C the flexural strength decreased slightly from approximately 80 to
      approximately 73 MPa (mean values), as temperature increased. That is a decay of
      less than 10%. At higher temperatures the flexural strength increased to a
      maximum of approximately 98 MPa at 500 degrees C, probably due to the closure of
      microcracks in the surface on account of the onset of viscous flow. A further
      increase of the temperature delivered again decreasing strength values. At its
      glass transition temperature the porcelain's flexural strength was approximately
      76 MPa which is only about 5% less than the value at room temperature.
      SIGNIFICANCE: In order to be able to evaluate the risk of fracture of
      ceramometallic crowns and bridges due to high temperature gradients and
      accompanying large transient thermal stresses in the veneer during the
      fabrication process, flexural strength values at high temperatures must be known.
      This study was carried out to fill this knowledge gap because to the authors'
      knowledge there was little published in the literature.

PMID- 12191671
TI  - A controlled randomised trial of t-UDCA as adjuvant to interferon for treatment
      of chronic hepatitis C: an interferon sparing effect of t-UDCA.
AB  - BACKGROUND: Combination of the cytoprotective effect of tauro-ursodeoxycholic
      acid (t-UDCA) with the antiviral effect of interferon may be more effective than
      interferon alone for treatment of chronic hepatitis C. METHODS: We randomised 106
      patients with chronic hepatitis C to interferon 3 MU/m(2)/3 times per week given
      alone (regimen A, n=51) or in combination with t-UDCA 10 mg/kg/day (regimen B,
      n=55) for 6 months followed by IFN dose tapering for further 6 months. Control
      liver biopsies were obtained 6 months after stopping treatment. RESULTS: At the
      end of the trial a similar proportion of patients had normal serum alanine
      aminotransferase activity (ALT) levels (41 and 44%) and negative viremia (42 and
      43%) with regimens A and B, respectively. The effect on liver histology was also
      similar, and the Knodell score decreased by 2.9+/-0.4 points with both regimens.
      During the dose tapering phase, the cumulative interferon dose to maintain ALT
      activity within the normal range was significantly lower for regimen B (142+/-4
      million units, MU) than for regimen A (180+/-12 MU, P<0.005). CONCLUSIONS:
      Adjuvant t-UDCA exerts an 'interferon sparing effect' that may be of value for
      patients intolerant to high dose interferon.

PMID- 12191672
TI  - Changes in hypervariable region 1 in patients with chronic hepatitis C of
      genotype 1b with biochemical response to interferon.
AB  - BACKGROUND/AIMS: The outcome of interferon (IFN) therapy of hepatitis C virus
      (HCV) infection can be classified as a complete viral response (CR), biochemical
      response (BR), or no response (NR). Why alanine aminotransferase (ALT) activity
      decreases in patients with BR despite viral persistence is unknown. METHODS: Of
      158 patients infected with HCV genotype 1b, all 20 patients with BR and 20 of the
      114 patients with NR, matched for viral load to the BR group, were studied. We
      sequenced nucleotides in the hypervariable region (HVR) of serum HCV RNA, and
      analyzed quasispecies of this region by the polymerase chain reaction and single
      strand conformation polymorphism (PCR-SSCP). RESULTS: In HVR 1, SSCP patterns
      differed after therapy; the major clone before therapy disappeared with therapy
      in eight of the 20 BR patients, but in none of the 20 NR patients (P=0.0033;
      Fisher's exact test). PCR products of HVR 1 from six patients were cloned before
      and after therapy, and 40 clones from each patient were sequenced each time.
      Results of cloning and sequencing were generally consistent with those of SSCP.
      For the six patients, a major clone could be identified both before and after
      therapy. In two patients with BR, there were many changes in the amino acid
      sequence of the major clone after IFN; in one patient with NR, mutations were not
      found. CONCLUSION: Changes in the major viral clone with IFN treatment may be
      related to the decrease in ALT activity in some patients, in spite of the
      continued presence of HCV RNA.

PMID- 12191673
TI  - Analysis of the entire nucleotide sequence of hepatitis B virus: characteristics
      of HBeAg-positive asymptomatic carriers, HBeAb positive asymptomatic carriers and
      patients with liver cirrhosis.
AB  - Entire nucleotide sequences of the HBV genome typical for various stages of HBV
      carriers are currently unknown. Comparison between conserved sequences in HBeAg
      positive asymptomatic carriers (HBeAg ASCs) and mutations characteristic for
      HBeAb-positive asymptomatic carriers (HBeAb ASCs) are of clinical importance. In
      this study, we determined the entire nucleotide sequences of the HBV genome of
      patients infected with genotype C (HBeAg ASCs, 11 cases; HBeAb ASCs, seven cases;
      patients with liver cirrhosis (LC), five cases). Mutations in the entire
      nucleotide sequences were found more frequently in HBeAb ASCs than in HBeAg ASCs.
      In the precore/core (preC/C) region, amino acid mutations were more frequent in
      HBeAb ASCs (3.03%) than in HBeAg ASCs (0.00%) and patients with LC (0.69%). It
      was suggested that the mutations in the preC/C region had a close relationship
      with clinical status of HBV carriers. Mutations of leucine to isoleucine at a.a.
      100 of the core region and of threonine to serine at a.a. 340 of the polymerase
      region were found frequently in HBeAb ASCs. In patients with LC, it was suggested
      that defective interfering particles (DI particles) play a role in the
      progression of stages. We conclude that attention should be given to mutations at
      a.a. 340 of the polymerase protein in addition to core protein.

PMID- 12191674
TI  - Restoration of thrombopoietin production after partial splenic embolization leads
      to resolution of thrombocytopenia in liver cirrhosis.
AB  - The aim of this study was to evaluate the relation between thrombopoietin (TPO)
      and thrombocytopenia in patients with liver cirrhosis and those with idiopathic
      portal hypertension (IPH) before and after partial splenic embolization (PSE). We
      examined changes in platelet counts, liver function, megakaryocyte function, and
      plasma TPO levels after PSE in 30 patients (20 with liver cirrhosis, and 10 with
      IPH). Platelet counts in both cirrhosis and IPH increased significantly 2 months
      after PSE (cirrhosis group, 4.0+/-1.9 vs. 7.5+/-4.4x10(4)/&mgr;l: P=0.0002; IPH
      group, 4.0+/-1.7 vs. 6.5+/-2.3x10(4)/&mgr;l: P=0.0042). Plasma TPO level and
      prothrombin time increased significantly and alanine aminotransferase level (ALT)
      and total bilirubin level decreased significantly 2 months after PSE in the
      cirrhosis group (plasma TPO level, 0.57+/-0.30 vs. 0.72+/-0.27 fmol/ml: P=0.024),
      but not in the IPH group (0.56+/-0.21 vs. 0.55+/-0.34 fmol/ml: P=0.94). Moreover,
      the score of megakaryocytes with platelet production, an index of platelet
      production by megakaryocytes in bone marrow, increased significantly in the
      cirrhosis group. TPO production in cirrhotic patients is restored after PSE,
      leading to the resolution of thrombocytopenia. But patients with IPH had no
      change in liver function, indicating that only decreased spleen volume was
      responsible for the improvement in platelet count.

PMID- 12191675
TI  - S100A6 protein as a marker for differential diagnosis of cholangiocarcinoma from
      hepatocellular carcinoma.
AB  - A new marker useful for differential diagnosis of cholangiocarcinoma (CC) from
      hepatocellular carcinoma (HCC) has been identified and investigated. cDNA clone
      for S100A6 (calcyclin) was identified as a upregulated gene in intrahepatic
      tumors by differential dot hybridization and Northern blot analysis using normal
      and tumor intrahepatic tissues. Significant increase in the expression level of
      S100A6 mRNA was recognized in intrahepatic tissues in three of three CC cases but
      none of six primary HCC. Immunohistochemical examination of the tumor tissues
      using monoclonal antibody specific to S100A6 showed that 14 of 18 (77.8%) CC
      tissue samples were positively stained but only two of 20 (10%) specimens from
      the patients with primary HCC were weakly stained. These results suggest that the
      levels of S100A6 mRNA expression and protein in the tissue specimens examined by
      Northern blot and immunohistochemical staining may be additional useful marker
      for the differentiation of CC from HCC.

PMID- 12191676
TI  - The fucosylation index of serum alpha-fetoprotein as useful prognostic factor in
      patients with hepatocellular carcinoma in special reference to chronological
      changes.
AB  - Aim of this study was to establish fucosylation index (FI) of alpha-fetoprotein
      (AFP) before and after initial treatment as a useful prognostic factor in
      patients with hepatocellular carcinoma (HCC). One hundred ninety-seven patients
      with HCC from 1990 to 2000, in whom an increment of serum AFP concentrations more
      than 30 ng/ml was observed before treatment, were examined in the present study.
      Enrolled patients with HCC underwent transcatheter arterial embolization,
      chemoembolization, percutaneous ethanol injection and/or percutaneous microwave
      coagulation therapy. The current patients status was confirmed as of the end of
      March 2001. FI was determined by crossed immunoaffinoelectrophoresis in the
      presence of Lens culinaris agglutinin (LCA). FI of AFP was defined as the
      percentage of the LCA-reactive species in total AFP (same as L3 fraction). When
      the tentative discriminating line of FI was set at 18%, the mean survival rate in
      the HCC group, whose FI-1 (before treatment) was higher than 18% (high FI), was
      significantly lower than that in another HCC group, whose FI-1 was equal to or
      less than 18% (low FI) by the generalized Wilcoxon test and the log rank test
      (P<0.0001). There were statistical significant differences of survival rate when
      FI-2 (2 months after treatment) and FI-3 (at the time of HCC recurrence or 2
      years after treatment in the case of no recurrence) were introduced in the same
      analysis. Additionally, statistical significant differences of survival rates
      were obtained between HCC groups with high and low FI-1 when the patient stage
      was limited to II, III, IVA or IVB. The HCC group, FI-1, FI-2 and FI-3 of which
      were persistently equal to or less than 18%, showed considerably better prognosis
      than the group, whose FI-1, FI-2 and FI-3 were persistently higher than 18%. The
      univariate analysis in the prognostic factor by the Cox's proportional hazards
      model showed that FI-1, FI-2 and FI-3 were independent prognostic factors. The
      present study indicates that measuring FI from the sera before and after the
      treatment serves as a new prognostic indicator and may improve prognostic
      estimates and appraisal of therapeutic outcome in patients with HCC.

PMID- 12191677
TI  - Effect of ursodeoxycholate-3,7-disulfate on biliary excretion of lithocholate-3-O
      glucuronide in Eisai hyperbilirubinemic rat (EHBR).
AB  - Biliary excretion of lithocholate-3-O-glucuronide and ursodeoxycholate-3,7
      disulfate is markedly impaired in EHBR, in which the multidrug resistance protein
      2 (Mrp2), a major ATP-dependent canalicular organic anion transporter, is
      impaired. We previously reported that biliary excretion of lithocholate-3-sulfate
      was enhanced by ursodeoxycholate-3,7-disulfate in Eisai hyperbilirubinemic rat
      (EHBR). In the present study, we examined the effect of ursodeoxycholate-3,7
      disulfate infusion on biliary excretion of lithocholate-3-O-glucuronide. Although
      in control rats, ursodeoxycholate-3,7-disulfate infusion had no effect on biliary
      lithocholate-3-O-glucuronide excretion, in EHBR it enhanced biliary lithocholate
      3-O-glucuronide excretion. These findings indicate that ursodeoxycholate-3,7
      disulfate may interact to the excretory pathway of lithocholate-3-O-glucuronide
      and enhances biliary excretion of lithocholate-3-O-glucuronide in EHBR.

PMID- 12191678
TI  - Bronchiolitis obliterans organizing pneumonia in a patient with primary biliary
      cirrhosis and rheumatoid arthritis treated with prednisolone.
AB  - A 62-year-old woman with primary biliary cirrhosis (PBC) and rheumatoid arthritis
      (RA) was examined at our hospital for a 2-week history of non-resolving fever,
      cough and malaise. Her chest radiograph revealed left lower lobe opacity. Various
      kinds of antibiotics were not effective and transbronchial biopsy revealed non
      specific inflammatory alveolar lesions. Chest radiograph at 14 days after
      admission revealed migration of the pulmonary opacity, suggesting bronchiolitis
      obliterans organizing pneumonia (BOOP), which responded well clinically and
      radiologically to oral corticosteroid therapy. BOOP may be one of the possible
      non-hepatic complications of PBC especially in patients associated with other
      connective tissue diseases.

PMID- 12191679
TI  - Eosionophilic pseudotumor of the liver due to Ascaris suum infection.
AB  - A case of eosinophilic pseudotumor of the liver due to Ascaris (A) suum is
      described in a 34-year-old-man with a high serum level of immunoglobulin E and
      hypereosinophilia ascribed to a history of atopic dermatitis since childhood.
      Multiple hepatic hypoechoic nodules detected by ultrasound were confirmed as low
      density nodules on computed tomography (CT), and as low and high signal intensity
      lesions on T1-and T2-weighted magnetic resonance imaging (MRI), respectively. CT
      during arteriography (CTA) and arterial portography revealed multiple nodules
      with ring-shaped enhancement and perfusion defect, respectively. Biopsied liver
      tissue specimens did not contain tumor cells or atypical cells; instead, they
      showed marked infiltration of eosinophils with necrosis and Charcot-Leyden
      crystals in the portal tracts and hepatic sinusoides, suggesting parasitic
      infection, although neither larvae nor eggs were detected. The diagnosis of
      visceral larva migrans (VLM) due to A. suum was based on immunoserological tests.
      The patient was a habitual consumer of raw bovine liver, which may explain the A.
      suum infection. After drug therapy with albendazole, the hypoechoic nodules
      disappeared. Differential diagnoses and the possible transfection route of A.
      suum are discussed.

PMID- 12191680
TI  - Melt extrusion: from process to drug delivery technology.
AB  - Starting from the plastic industry, today melt extrusion has found its place in
      the array of pharmaceutical manufacturing operations. This article reviews the
      process technology with regard to the set up and specific elements of the
      extruder as well as its application. Melt extrusion processes are currently
      applied in the pharmaceutical field for the manufacture of a variety of dosage
      forms and formulations such as granules, pellets, tablets, suppositories,
      implants, stents, transdermal systems and ophthalmic inserts. As a specific area
      the manufacture of solid dispersions, in particular, solid molecular dispersions
      using the melt extrusion process is reviewed. Melt extrusion is considered to be
      an efficient technology in this field with particular advantages over solvent
      processes like co-precipitation. Potential drawbacks like the influence of heat
      stress and shear forces on the drug active have been overcome in a number of
      examples with drugs of different chemical structure. Examples of suitable
      excipients and recent findings like self-emulsifying preparations are presented.
      The article concludes with a number of published examples of melt extrudates
      applying the principle of solid molecular dispersions. Improved bioavailability
      was achieved again demonstrating the value of the technology as a drug delivery
      tool.

PMID- 12191681
TI  - Tumor accumulation of gadolinium in lipid-nanoparticles intravenously injected
      for neutron-capture therapy of cancer.
AB  - Gadolinium-incorporating lipid-nanoemulsions (Gd-nanoLE) for neutron-capture
      therapy were prepared. As a more convenient administration route than the
      intraperitoneal (i.p.) injection previously reported, the intravenous (i.v.)
      injections in tumor-bearing hamsters were carried out at an administration volume
      of 1 ml, which was the maximum tolerable injection volume of an i.v. injection
      and half that of an i.p. injection. When the standard-Gd-nanoLE of 1.5 mgGd/ml
      was administered, the absolute bioavailability in the i.p. injection was 57%,
      probably resulting from incomplete absorption from the peritoneal cavity into the
      blood stream. The biodistribution data revealed that the i.v. injection had three
      advantages over the i.p. injection, namely, a faster and higher accumulation of
      Gd-nano LE, and a more extended retention time in the tumor. Two i.v. injections
      of the standard-Gd-nanoLE with a 24h interval doubled the tumor accumulation of
      Gd, resulting in 49.7 microg Gd/g wet tumor 12h after administration. By using a
      twofold Gd-enriched formulation (High-Gd-nanoLE) of 3.0 mgGd/ml in the repeated
      administration schedule, the accumulation was doubled again, reaching 101 microg
      Gd/g wet tumor. This level was comparable to the maximum level in the single i.p.
      injection previously reported. These results demonstrated that i.v. injection
      could be an alternative to i.p. injection as an administration route.

PMID- 12191682
TI  - Microparticles derived from marine sponge collagen (SCMPs): preparation,
      characterization and suitability for dermal delivery of all-trans retinol.
AB  - Collagen microparticles were prepared using marine sponge collagen. For this
      purpose a previous method by Rossler et al. (J. Microencapsul. 12 (1995) 49) of
      emulsification and cross-linking of native calf collagen was modified. The
      modified method for sponge collagen microparticles (SCMPs) achieved a yield of
      10%. Scanning electromicroscopic photographs showed spherical particles with a
      diameter of 120-300 nm and photon correlation spectroscopic measurements
      indicated particle size range from 126 (+/-2.9) to 2179 (+/-342) nm. This broad
      size distribution was caused by some agglomerates that could not be destroyed by
      ultrasonication. The surface charge was measured as a function of pH. At pH 2.8
      the particles were nearly uncharged, at pH 9.0 the particles showed a strong
      negative charge of about -60 mV. The preformed SCMPs were loaded by adsorption of
      all-trans retinol. A loading of up to 8% was obtained. Retinol-loaded SCMPs were
      incorporated into hydrogels and drug stability was investigated. The in vitro
      penetration of retinol into hairless mice skin in this formulation was compared
      to retinol formulations without microparticles. The SCMPs had no influence on the
      chemical stability of retinol in the hydrogel. The dermal penetration of retinol
      into the skin increased significantly by approximately two-fold.

PMID- 12191683
TI  - Development and characterization of buccoadhesive nifedipine tablets.
AB  - The buccoadhesive controlled-release tablets for delivery of nifedipine were
      prepared by direct compression of carboxymethyl cellulose (CMC) with carbomer
      (CP), which showed superior bioadhesion properties compared to
      polyvinylpyrrolidone (PVP), polyvinyl alcohol (PVA), hydroxypropylmethyl
      cellulose (HPMC), and acacia in a modified tensiometry method in vitro. The
      tablets containing 30mg of nifedipine and various amounts of CMC and CP showed a
      zero-order drug release kinetic. The adhesion force was significantly affected by
      the mixing ratio of CP:CMC in the tablets. The weakest and highest adhesion force
      was observed at the mixing ratios of 1:0 and 8:2 of CP:CMC, respectively. The
      tablets containing 15% CMC and 35% CP adhered for over 8h to the upper gums of
      six healthy human volunteers. These tablets released about 56% of the loaded drug
      after 8h in vivo with a rate of 2.17h(-1) and were perfectly tolerated, while
      they released about 100% of their content after the same time with a rate of
      3.49h(-1) in vitro. A good correlation (r(2)=0.989) was observed between drug
      released in vitro and in vivo.

PMID- 12191684
TI  - The influence of dilution of topical semisolid preparations on hydrocortisone
      permeation through excised human stratum corneum.
AB  - Dilution of semisolid preparations, in order to tailor the formulations to the
      needs of the patients, was thought to be associated with a number of dangers, one
      of which is the unpredictable alteration of activity. In the present study the
      influence of dilution on hydrocortisone permeation through excised human stratum
      corneum was investigated. The permeation profiles of hydrocortisone from various
      cream bases (diluted and undiluted) were found to be very similar with no
      significant differences. This result was in accordance with the lack of
      interaction between the tested bases and the structure of stratum corneum as
      shown by differential scanning calorimetry experiments. Thus, the permeability of
      stratum corneum, which was not affected by the cream bases, is the rate limiting
      step for drug permeation. However, it could be shown that dilution of Soventol
      cream (placebo with 1% hydrocortisone) which is known to contain isopropyl
      myristate as permeation enhancer reduces drug permeation. The reduced
      hydrocortisone permeation is believed to be due to reduced enhancer
      concentration.

PMID- 12191685
TI  - Optimized transdermal delivery of ketoprofen using pH and hydroxypropyl-beta
      cyclodextrin as co-enhancers.
AB  - The role of pH and pK(a) of ionizable drugs in transdermal delivery has been well
      documented by the pH partition hypothesis. Similarly the role of pH in
      complexation has also been addressed by many studies. Reports contrary to the
      well believed theory that both molecular encapsulation by hydroxypropyl-beta
      cyclodextrin (HP-beta-CD) and transdermal delivery are considered a phenomenon of
      unionized drug species prompted investigation into the combined effect of pH and
      HP-beta-CD on transdermal delivery of ketoprofen. In order to optimize the
      delivery of ketoprofen, solubility studies and permeation studies were conducted
      in vitro at pH 3.0, 4.5 and 6.0 at various concentrations of cyclodextrin. The
      stability constants for unionized and ionized drugs were calculated. The
      solubility of the ionized complex of the drug was 2.5 fold greater than the
      unionized complex. The flux increased linearly with increasing HP-beta-CD
      concentration at all the pH values. However, the increase was significant at pH
      6.0 where the drug is predominantly in the ionized state. The flux of the ionized
      drug at 10% w/v HP-beta-CD concentration was enhanced to an order of
      approximately eight times compared to the intrinsic permeability of the unionized
      drug. The study shows that at higher pH, HP-beta-CD can be utilized to achieve
      greater transdermal flux of ketoprofen.

PMID- 12191686
TI  - Comparison of skin distribution of hydrolytic activity for bioconversion of beta
      estradiol 17-acetate between man and several animals in vitro.
AB  - We have investigated the distribution of hydrolytic enzymes which metabolize beta
      estradiol 17-acetate (EA) to beta-estradiol (E) in man and animal skins in vitro.
      The distribution of hydrolytic enzymes in human cadaver, hairless dog, rat and
      hairless mouse skin, was investigated by a skin-slicing technique. We performed
      histological studies with hematoxylin and eosin stain. The highest amount of
      metabolite (E) appeared in the layers of 80-120 microm from the skin surface, the
      basement layer in human skin, while the amount of metabolite was distributed
      evenly in the hairless dog skin from 0 to 180 microm. In the rat and hairless
      mouse skin, on the other hand, peak levels of metabolite were observed in the
      basement layer of dermis, the surrounding area of the cutaneous plexus. The total
      metabolic activities in the area of epidermis in human, hairless dog and hairless
      mouse skin were 2.59, 8.03 and 0.33 x 10(-4) microg/ml/microm/h, respectively.
      The values in whole skin layers in the hairless dog and hairless mouse skin were
      3.35 and 1.85 x 10(-4)microg/ml/microm/h, respectively. EA transported across the
      human and hairless dog skin can be effectively metabolized before entering the
      capillary. Among animal models investigated, hairless dog skin might be the most
      facile model in simulating drug metabolism for human skin under the clinical (in
      vivo) conditions. Hairless mouse skin, on the other hand, was also an excellent
      model in excised human skin under in vitro conditions.

PMID- 12191687
TI  - Monolithic matrix type transdermal drug delivery systems of pinacidil
      monohydrate: in vitro characterisation.
AB  - The monolithic matrix type transdermal drug delivery systems of pinacidil
      monohydrate (PM) were prepared by film casting technique on mercury substrate and
      characterised in vitro by drug release studies using paddle over disc assembly,
      skin permeation studies using Keshary and Chein diffusion cell on albino rat skin
      and drug-excipient interaction analysis. Four formulations were developed which
      differed in the ratio of matrix forming polymers, Eudragit RL-100 and PVP K-30,
      i.e. 8:2, 4:6, 2:8 and 6:4 and were coded as B-1, B-2, B-3 and B-4, respectively.
      All the four formulations carried 20% w/w of PM, 5% w/w of plasticiser, PEG-400
      and 5% w/w of DMSO (based on total polymer weight) in isopropyl alcohol:
      dichloromethane (40:60) solvent system. Cumulative % of drug released in 48 h
      from the four formulations was 63.96, 55.95, 52.26 and 92.18%. The corresponding
      values for cumulative amount of drug permeated for the said formulations were
      57.28, 50.35, 46.38 and 86.54%, respectively. On the basis of in vitro drug
      release and skin permeation performance, formulation B-4 was found to be better
      than the other three formulations and it was selected as the optimised
      formulation. The interaction studies carried out by comparing the results of
      assay, ultraviolet, infrared and TLC analyses for the pure drug, medicated and
      placebo formulations indicated no chemical interaction between the drug and
      excipients.

PMID- 12191688
TI  - Influence of surface charge density on protein adsorption on polymeric
      nanoparticles: analysis by two-dimensional electrophoresis.
AB  - Plasma protein adsorption is regarded as a key factor for the in vivo organ
      distribution of intravenously administered colloidal drug carriers, and strongly
      depends on their surface characteristics, e.g. surface hydrophobicity or charge.
      A range of polymeric nanoparticles with a steep variation of the surface charge
      density was synthesized as model drug carriers. Physicochemical parameters, i.e.
      particle size, surface charge density, hydrophobicity and surface topography were
      determined. Two-dimensional electrophoresis (2-DE) was employed for determination
      of particle interactions with human plasma proteins. Increasing surface charge
      density showed an increase in plasma protein adsorption, but did not show
      differences in the detected protein species. For the first time it was possible
      to show plasma protein adsorption patterns on a range of nanoparticles with
      variation of only one parameter, i.e. the charge, while size and surface
      hydrophobicity remain practically unchanged. The knowledge about the interactions
      of proteins with particulate surfaces can be exploited for the future controlled
      design of colloidal drug carriers and possibly in the controlled creation of
      biocompatible surfaces of other devices that come into contact with proteins
      (e.g. microparticles and implants).

PMID- 12191689
TI  - Estimating vapor pressure curves by thermogravimetry: a rapid and convenient
      method for characterization of pharmaceuticals.
AB  - The purpose of this study was to investigate a rapid method for the evaluation of
      vaporization characteristics for selected benzoic acid derivatives. The compounds
      studied in this context were the ortho-, meta- and para-derivatives of hydroxy
      and amino benzoic acids. Calculations for the order of reaction were first
      carried out for each of the compounds using methyl paraben as the calibration
      standard. Those compounds undergoing zero order, non-activated evaporation
      processes, were analyzed by the Antoine and Langmuir equations, conjointly. The
      coefficient of vaporization was obtained as 1.2 x 10(5)+/-0.8 Pakg
      (0.5)mol(0.5)s(-1)m(-2)K(-0.5). The vapor pressure values were used to determine
      the Antoine constants using the SPSS 10.0 software. This study attempts to
      outline a comprehensive thermogravimetric technique for vapor pressure
      characterization of single-component systems.

PMID- 12191690
TI  - Comparative study of ibuproxam complexation with amorphous beta-cyclodextrin
      derivatives in solution and in the solid state.
AB  - The complexing, solubilizing and amorphizing abilities toward ibuproxam (a poorly
      water-soluble anti-inflammatory agent) of some randomly substituted amorphous
      beta-cyclodextrin derivatives (i.e. methyl- (MebetaCd), hydroxyethyl- (HEbetaCd),
      and hydroxypropyl- (HPbetaCd) beta-cyclodextrins) were investigated and compared
      with those of the parent beta-cyclodextrin. Equimolar drug-cyclodextrin solid
      systems were prepared by blending, cogrinding, coevaporation, and
      colyophilization. Drug-carrier interactions were studied in both the liquid and
      solid state by phase solubility analysis, supported by molecular modelling,
      differential scanning calorimetry, X-ray powder diffractometry, Fourier transform
      infrared spectroscopy and scanning electron microscopy. All the betaCd
      derivatives showed greater solubilizing efficacies toward ibuproxam than the
      parent one, due to their higher water solubility. On the contrary, a clear
      reduction of complexing ability was observed, indicative of some steric
      interferences to drug inclusion due to the presence of substituents, as confirmed
      by molecular modelling studies. However, this negative effect was not reflected
      in the dissolution behaviour (evaluated according to the dispersed amount method)
      of their solid binary systems, probably thanks to the greater amorphizing
      properties shown (DSC and X-ray analyses) by betaCd derivatives. In fact their
      dissolution efficiencies were not significantly different (MebetaCd) or only
      slightly lower (HEbetaCd and HPbetaCd) than those of the corresponding products
      with beta-cyclodextrin. Colyophilized products were in all cases the most
      effective, followed by coground and coevaporated systems, whose dissolution
      efficiencies were over four times higher than the corresponding physical mixtures
      and about 15 times higher than the pure drug.

PMID- 12191691
TI  - A study of release mechanisms of different ophthalmic drugs from erodible ocular
      inserts based on poly(ethylene oxide).
AB  - When topical controlled delivery of ophthalmic drugs is realised via erodible
      inserts, drug bioavailability is maximised, if release is controlled exclusively
      by insert erosion, since parallel mechanisms which increase the release rate,
      also increases the dose fraction cleared from the precorneal area by tear fluid
      draining. The respective contributions of diffusion and erosion to the release
      mechanism of different drugs, namely, prednisolone (PDS), oxytetracycline
      hydrochloride (OTH) and gentamicin sulfate (GTS), from erodible ocular inserts
      based on poly(ethylene oxide) (PEO) of molecular weight 400 or 900kDa was
      determined by an in vitro technique adequate to predict the release mechanism in
      vivo. PDS and OTH were released with erosion-controlled kinetics. With
      therapeutic doses of these drugs in the inserts (0.3mg, 1.5%), the possibility of
      a purely erosive mechanism was shown to rely upon drug-PEO molecular
      interactions, which limit drug diffusion in the swollen matrix. This was the case
      with OTH, for which strong interactions with PEO were measured, whereas some
      contribution from the parallel diffusive mechanism was evidenced for PDS, which
      showed weaker interactions with polymer. Such a contribution disappeared when the
      PDS concentration in the insert was increased to 6%, which suggested that the
      erosive mechanism is favoured by a drug concentration in the hydrated insert
      substantially higher than solubility. On the other hand, the release of about 50%
      GTS dose was controlled by diffusion, due to the high water solubility of this
      drug, accompanied by weak drug-PEO interactions. In this case the residence time
      of drug in the precorneal area is expected to be significantly shorter than that
      of the PEO carrier.

PMID- 12191692
TI  - Controlled release of triprolidine using ethylene-vinyl acetate membrane and
      matrix systems.
AB  - The studies on the permeability of triprolidine through ethylene-vinyl acetate
      (EVA) copolymer membrane using two-chamber diffusion cell was carried out to
      develop the controlled delivery system. To evaluate the effect of drug
      concentration in reservoir, polyethylene glycol (PEG) 400 was added to saline
      solution as a solubilizer and a sink condition was maintained in the receptor
      solution. The permeation rate of drug through EVA membrane was proportional to
      PEG 400 volume fraction. A linear relationship existed between the permeation
      rate and the reciprocal of the membrane thickness. Triprolidine-containing matrix
      was fabricated with EVA copolymer to control the release of the drug. The
      plasticizers was added for preparing the pore structure of EVA membranes to
      increase the drug release. The effects of PEG 400, vinyl acetate (VA) contents of
      EVA, membrane thickness, drug concentration, temperature, and plasticizers, on
      drug release were studied. The release rate of drug from the EVA matrix increased
      with PEG 400 volume fraction, increased temperature and drug loading doses. An
      increased vinyl acetate comonomer content in EVA membrane increased the drug
      release rate and permeability coefficient. Among the plasticizers used such as
      alkyl citrates and phthalates, tetra ethyl citrate showed the best enhancing
      effects showing the enhancement factor of 1.88. The release of triprolidine from
      the EVA matrix follows a diffusion controlled model, where the quantity released
      per unit area is proportional to the square root of time. The controlled release
      of triprolidine could be achieved using the EVA polymer including the
      plasticizer.

PMID- 12191693
TI  - Parenteral emulsions stabilized with a mixture of phospholipids and PEG-660-12
      hydroxy-stearate: evaluation of accelerated and long-term stability.
AB  - Different emulsion formulations were prepared using phospholipids (Lipoid S57)
      and PEG-660-12-hydroxy-stearate (Solutol HS15) as single emulsifiers or in
      mixtures. The accelerated stability after autoclaving, freezing and
      centrifugation was investigated. The long-term stability was also studied at
      different temperatures (4, 20, and 37 degrees C) for 8 months. Emulsion
      stabilized with phospholipids displayed a stable behavior after the autoclaving
      and centrifugation, but it broke down after the freezing process. In mixture with
      Solutol HS15, however, the emulsion showed appropriate shelf stability at
      different temperatures for 8 months. A change in the particle size of the
      emulsion prepared only with Solutol HS15 was observed after centrifugation
      (slight) and after autoclaving (marked). In contrast to phospholipid emulsion,
      this emulsion (with only Solutol HS15) was less prone to breaking down after the
      freezing, as no complete phase separation was observed. The results obtained
      using an emulsifier mixture revealed that a combination of an anionic surfactant
      (phospholipids) and non-ionic surfactant (PEG-660-12-hydroxy-stearate) improves
      the emulsion's stability, compared to the emulsion's stability prepared using
      only a single emulsifier. However, no direct correlation could be found between
      the accelerated and the long-term stability data.

PMID- 12191694
TI  - Liposomes produced in a pilot scale: production, purification and efficiency
      aspects.
AB  - Intensive efforts have been made to establish a novel, scalable liposomal
      preparation technique suitable for the entrapment of even large proteins into
      liposomes. We have developed a new technique based on the principles of the
      ethanol injection technique. Herein, the principal item is the crossflow
      injection module, specifically designed for this purpose. This unit has the
      benefit of defined and characterized injection streams and permits liposome
      manufacture regardless of production scale, as scale is determined only by the
      free disposable vessel volumes. Previous publications demonstrated that the
      crossflow injection technique that we have developed meets all of the above
      mentioned requirements. The present paper describes the entire three-step
      production process, consisting of encapsulation, separation of non-entrapped
      protein by continuous crossflow filtration, and retrieval of rh-Cu/Zn-SOD by
      additional filtration. Results of consecutive lots were compared, based on well
      defined quality criteria.

PMID- 12191695
TI  - Preparation and characterization of microparticles containing peptide produced by
      a novel process: spray freezing into liquid.
AB  - The objective of this study is to evaluate excipient type on the physicochemical
      properties of insulin microparticles produced by spray freezing into liquid
      (SFL). A novel process was developed to produce microparticles containing
      bioactive peptides and proteins. The microparticles were formed by atomization of
      an aqueous feed solution containing insulin beneath the surface of a cryogenic
      liquid (e.g. liquid nitrogen). In this study, bovine insulin was dissolved in
      deionized water alone or with tyloxapol, lactose or trehalose. The aqueous
      solution was sprayed directly into liquid nitrogen through a polyetheretherketone
      capillary nozzle under high pressure to form frozen microparticles.
      Lyophilization was used to sublime the ice. The SFL insulin powder was
      characterized by different techniques, including X-ray diffraction, reverse-phase
      high pressure liquid chromatography, size exclusion chromatography, scanning
      electron microscopy (SEM), particle size distribution and surface area. The mean
      diameter of the insulin microparticles was 5-7 microm. SEM revealed that the
      microparticles were highly porous, and the morphology of the microparticles was
      influenced by the excipient type. The total surface area of the insulin
      microparticles ranged from 20 to 40 m(2)/g, and the magnitude depended on the
      specific composition and total solids content of the aqueous feed solution. X-ray
      diffraction results indicated lack of crystallinity. No change in the level of
      the degradation product, A-21 desamido insulin, was found in the SFL insulin
      samples processed alone or with trehalose or tyloxapol. Similarly, no change in
      formation of high molecular weight transformation products (e.g. covalent insulin
      dimer) was detected in the samples processed with excipients. The results
      demonstrated that SFL is a feasible technique for forming porous microparticles
      containing insulin. The physicochemical properties of insulin were preserved by
      the SFL technique.

PMID- 12191696
TI  - Polyvinylalcohol substituted with triethyleneglycolmonoethylether as a new
      material for preparation of solid dispersions of hydrophobic drugs.
AB  - Among the different methods used to increase the aqueous drug solubility, the
      preparation of a solid dispersion with a soluble carrier represents an
      interesting formulative approach. We substituted polyvinylalcohol with
      triethyleneglycolmonoethylether and obtained a suitable material for the
      formulation of a solid dispersion of progesterone, by spray-drying. In
      particular, we evaluated the influence of the polyvinylalcohol substitution
      degree and the polymer-drug weight ratios in the preparative mixture on the
      progesterone dissolution rate in the aqueous environment.

PMID- 12191697
TI  - The influence of multivalent phosphate structure on the properties of ionically
      cross-linked chitosan films for controlled drug release.
AB  - The aim of this paper was to investigate the electrostatic interactions between
      multivalent phosphates (phosphate (Phos), pyrophosphate (Pyro) and
      tripolyphosphate (TPP)) and chitosan, as well as the influence of electrostatic
      interactions on the properties of chitosan films ionically cross-linked by the
      above mentioned phosphates. The charge number of Phos was too low to interact
      with chitosan, while Pyro and TPP with more negative charges showed a significant
      ability to ionically cross-link chitosan. Solution pH played an important role on
      the charge numbers carried by Pyro, TPP and chitosan, especially for
      Pyro/chitosan. For instance, at pH less than 2.0 the interaction between Pyro and
      chitosan disappeared, while for TPP/chitosan even in solutions at pH less than
      0.5 it still existed. Media pH and ionic strength also had a significant
      influence on the properties of cross-linked chitosan film with multivalent
      phosphates. Usually these films swelled and drug was released quickly in acidic
      conditions (such as in simulated gastric fluid) while under neutral conditions
      (such as in simulated intestinal fluid) they remained in a shrinkage state and
      drug was released slowly. Compared to TPP/chitosan films, Pyro/chitosan films
      exhibited much better pH-sensitive swelling and controlled release properties due
      to their relatively weak electrostatic interaction. The same reasoning was used
      to explain the significant acceleration of Pyro/chitosan film swelling and model
      drug release observed on adding sodium chloride. These films may be promising for
      site-specific drug delivery in the stomach.

PMID- 12191698
TI  - The effect of budesonide particle mass on drug particle detachment from carrier
      crystals in adhesive mixtures during inhalation.
AB  - The different fine particle fractions (FPFs) that are obtained, when different
      dry powder inhalers (DPIs) are used for the same powder formulation at the same
      flow rate, is the result of different powder de-agglomeration efficiencies for
      these DPIs. For adhesive mixtures, this is the efficiency with which the kinetic
      energy of the air flow through the DPI is converted into separation forces that
      detach drug particles from carrier crystals. We investigated the effect of drug
      particle diameter (mass) on drug-carrier separation during inhalation with three
      different inhalers (Sofotec Novolizer, Inhalator Ingelheim and a special test
      inhaler), at two different flow rates (30 and 60l/min). Two different size
      fractions were used as carrier material (45-63 and 100-150 microm). We measured
      decreasing amounts of residual drug on the carrier crystals after inhalation with
      increasing drug particle mass for all inhalers at both flow rates. The observed
      trends were the same for both carrier fractions. The decrease in residual drug on
      carrier is in agreement with increasing FPFs in an Erweka impactor. However, it
      has been calculated that the magnitude of the effect decreases with increasing de
      agglomeration efficiency.

PMID- 12191699
TI  - Intramolecular cyclization of diketopiperazine formation in solid-state enalapril
      maleate studied by thermal FT-IR microscopic system.
AB  - The pathway of diketopiperazine (DKP) formation of solid-state enalapril maleate
      has been studied by using a novel Fourier transform infrared microspectroscope
      equipped with a thermal analyzer (thermal FT-IR microscopic system). The
      thermogram of the conventional differential scanning calorimetry (DSC) method was
      also compared. The results show new evidence of IR peaks at 3250 cm(-1) (the
      broad O-H stretching mode of water), and at 1738 and 1672 cm(-1) (the carbonyl
      band of DKP), indicating DKP formation in enalapril maleate via intramolecular
      cyclization. Moreover, the disappearance of IR peaks from enalapril maleate at
      3215 cm(-1) (the secondary amine), 1728 cm(-1) (the carbonyl group of carboxylic
      acid), and 1649 cm(-1) (the carbonyl stretching of tertiary amide) also confirmed
      the DKP formation. The thermal FT-IR microscopic system clearly evidenced that
      the DKP formation in enalapril maleate started from 129 degrees C, and reached a
      maximum at 137 degrees C. This result was also confirmed by the conventional DSC
      thermogram of the compressed mixture of KBr powder and enalapril maleate, in
      which an endothermic peak at 144 degrees C with an extrapolated onset temperature
      at 137 degrees C was observed. This strongly suggests that the thermal FT-IR
      microscopic system was able to qualitatively detect the formation of DKP
      derivatives in solid-state enalapril maleate via intramolecular cyclization.

PMID- 12191701
TI  - LC method for the analysis of Oxiconazole in pharmaceutical formulations.
AB  - A LC method has been developed for the quantitative determination of Oxiconazole
      (Ox) in bulk form, lotion and cream pharmaceutical formulations. The method
      validation yielded good results including the range, linearity, precision,
      accuracy, recovery, specificity, robustness, limit of quantitation and limit of
      detection. The LC separation was carried by reversed phase chromatography using a
      LiChrocart C(8) column (125 mm x 4.0 mm i.d., 5 microm particle size). The mobile
      phase was composed of methanol-0.02 M ammonium acetate buffer (85:15 v/v), pumped
      isocratically at flow rate 1 ml min(-1). The detection was carried out on UV
      detector at 254 nm. The calibration curve for Ox was linear from 40.0-140.0
      microg ml(-1) range. The precision of this method, calculated as the relative
      standard deviation (R.S.D.) was 1.57% for lotion and 0.71% for cream. The R.S.D.
      values for intra- and inter-day precision studies were 0.57 and 1.34%,
      respectively. The recovery of the drug ranged between 98.84-102.2% (lotion) and
      100.54-101.59% (cream). The stability indicating capability of the assays was
      proved using forced degradation. Chromatograms showed Ox well resolved from the
      degradation product.

PMID- 12191702
TI  - Polymeric membrane ion-selective electrode for determination of bismuth (III) in
      pharmaceutical substances.
AB  - A PVC-based membrane of tridecylmethylammonium chloride reveals a Nernstian
      potentiometric response (with slope of 55 mV/decade and a correlation coefficient
      of 0.99) for complex of bismuth (III) with ethylenediaminetetraacetate-anion
      [Bi(EDTA)](-) over a wide concentration range (1 x 10(-1) to 3 x 10(-5) mol/l).
      The potential of this electrode is independent of pH in the range of 4.0-11.0. It
      has a fast response time of about 30 s and was used for a period of 3 months with
      good reproducibility. The detection limit of this membrane electrode was 1 x 10(
      5) M. This sensor exhibits a very good selectivity for [Bi(EDTA)] over a wide
      variety of complex metal ions with ethylenediaminetetraacetic acid. The proposed
      electrode has been used in the direct potentiometric monitoring of bismuth (III)
      in stomach anti-acids.

PMID- 12191703
TI  - Correlation of tramadol pharmacokinetics and CYP2D6*10 genotype in Malaysian
      subjects.
AB  - The aim of the present study is to investigate the influence of the CYP2D6*10
      allele on the disposition of tramadol hydrochloride in Malaysian subjects. A
      single dose of 100 mg tramadol was given intravenously to 30 healthy orthopaedic
      patients undergoing various elective surgeries. After having obtained written
      informed consents, patients were genotyped for CYP2D6*10: the most common CYP2D6
      allele among Asians by means of allele-specific polymerase chain reaction. The
      presence of other mutations (CYP2D6*1, *3, *4, *5, *9 and *17) was also
      investigated. Tramadol was extracted from 1 ml serum with an n-hexane:
      ethylacetate combination (4:1) after alkalinisation with ammonia (pH 10.6). Serum
      concentrations were measured by means of high-performance liquid chromatography.
      The pharmacokinetics of tramadol was studied during the 24 h after the dose. As
      among other Asians, the allele frequency for CYP2D6*10 among Malaysians was high
      (0.43). Subjects who were homozygous for CYP2D6*10 had significantly (P=0.046)
      longer mean serum half-life of tramadol than subjects of the normal or the
      heterozygous group (Kruskal-Wallis test). When patients were screened for the
      presence of other alleles, the pharmacokinetic parameter values were better
      explained. CYP2D6 activity may play a main role in determining tramadol
      pharmacokinetics. The CYP2D6*10 allele particularly was associated with higher
      serum levels of tramadol compared with the CYP2D6*1 allele. However, genotyping
      for CYP2D6*10 alone is not sufficient to explain tramadol disposition.

PMID- 12191704
TI  - Formation of novel toxic compounds from oxidative interaction between salsolinol
      and cysteine.
AB  - The electrochemically-driven oxidation of salsolinol (SAL) precedes via a 2e,
      2H(+) process to produce the corresponding o-quinone (E) intermediate which has a
      very short lifetime and can be scavenged by cysteine to give the corresponding
      adduct cysteinyl salsoninol (F). F is more easily oxidized to the corresponding o
      quinone (G) followed by cyclization resulting in the formation of the quinone
      imine intermediate (H). H can then undergo series of nucleophilic addition and
      oxidation reactions to produce a very complicated mixture of products including
      some dihydrobenzothiazines. Six of these products have been isolated and
      identified. Central administration of these compounds into laboratory mice
      revealed that three of them are fairly toxic and evoke profound behavioral
      responses.

PMID- 12191705
TI  - A chiral HPLC method for the determination of low amounts of D-carnitine in L
      carnitine after derivatization with (+)-FLEC.
AB  - An indirect enantioseparation method for robust and precise determination of D
      Carnitine (D-C) in L-Carnitine (L-C) in the range of 0.1-1.0% is presented. The
      method is based on derivatization of Carnitine with (+)-[1-(9-fluorenyl)-ethyl]
      chloroformate ((+)-FLEC). The two diastereomers are subsequently separated of on
      an octadecyl column using detection of the eluent by fluorescence (260
      excitation, 310 nm emission monitoring). This procedure can be calibrated
      conveniently by diluting the derivatization solution of the sample. Hence, D-C
      was determined indirectly through quantification of L-C thereby strongly
      increasing the robustness and reducing the costs. During the development of the
      method a study was undertaken to prove that the method is suitable to determine
      enantiomeric purity of L-C indeed. Moreover, the method was validated according
      to the ICH guidance, which required the additional performance of a collaborative
      study. The proposed assay can be carried out using an autoinjector because the
      derivatives are very stable. Hence, we believe that this method will become
      popular for reliable determination of enantiomeric purity of L-C.

PMID- 12191707
TI  - Investigation of the effects of grinding and co-grinding on physicochemical
      properties of glisentide.
AB  - The purpose of the present study was to investigate the possibility of improving
      the dissolution properties of glisentide, a poorly water-soluble antidiabetic
      drug, by grinding in a high energy micromill, alone or in mixture with
      polyvinylpyrrolidone (PVP). Conventional and modulated differential scanning
      calorimetry (DSC, MDSC), thermogravimetry (TGA), X-ray powder diffraction (XRD),
      Fourier transform infrared spectroscopy (FT-IR), hot-stage FT-IR thermomicroscopy
      and scanning electron microscopy (SEM) were used to characterize the drug solid
      state, whereas its dissolution rates were determined according to the dispersed
      amount method. The techniques utilized enabled exclusion of polymorphism
      phenomena as a consequence of mechanical treatment, and revealed a progressive
      drug amorphization during grinding. In particular, MDSC allowed a clear
      determination of the glass transition temperature of the amorphous drug, enabling
      separation of glass transition from enthalpic relaxation. The amorphous state of
      the ground drug was the main responsible factor for the obtained 100% dissolution
      efficiency increase in comparison with the untreated drug. Further significant
      increases in dissolution properties, directly related to the polymer content in
      the mixture, were obtained by co-grinding with PVP, whose presence clearly
      favored drug amorphization, allowing a strong reduction of time and frequency of
      grinding necessary for obtaining complete drug amorphization.

PMID- 12191706
TI  - Voltammetric analysis of trazodone HCl in pharmaceuticals and biological fluids.
AB  - The voltammetric behavior of trazodone (TRZ) HCl was studied using direct current
      (DC(t)), differential pulse (DPP) and alternating current (AC(t)) polarography.
      The drug manifests cathodic waves over the pH range of 10-14. The waves were
      characterized as being irreversible, diffusion-controlled with limited adsorption
      properties. At pH 10, the diffusion current-concentration relationship was found
      to be rectilinear over the range 4-32 and 0.8-24 microg ml(-1) using DC(t) and
      DPP modes, respectively, with minimum detectability (S/N=2) of 0.104 microg ml(
      1) (2.45 x 10(-6) M) and 0.314 microg ml(-1) (7.397 x 10(-6) M) using the DPP and
      DC(t) modes, respectively. The diffusion-current constant (I(d)) is 4.31+/-0.02
      (n=6). The proposed method was successfully applied to the determination of the
      studied compound either in pure form or in formulations. The results obtained
      were favorably compared with those given using a reference method. Furthermore,
      the proposed method was applied to the determination of TRZ in spiked human urine
      and plasma adopting the DPP technique. No prior extraction step is needed in case
      of urine. The percentage recoveries were 98.43+/-0.79 and 97.44+/-0.705 (n=4) in
      spiked human urine and plasma, respectively. A pathway for the electrode reaction
      was postulated.

PMID- 12191709
TI  - Simultaneous determination of amphetamine and one of its metabolites by HPLC with
      electrochemical detection.
AB  - A high-performance liquid chromatographic method coupled with electrochemical
      detector was developed for the separation and quantitation of amphetamine and one
      of its metabolites, the 4-hydroxynorephedrine. The pre-column derivatisation of
      these compounds was carried out with 2,5-dihydroxybenzaldehyde as electroactive
      labelling reagent, in presence of Borohydride Exchange Resin. The new synthetic
      method developed was fast, clean and high yielding. The analysis was performed in
      isocratic mode on a reversed phase column 5 microm Hypersil ODS RP-18, 15 cm,
      using as a mobile phase methanol-NaH(2)PO(4) buffer (50 mM, pH 5.5)(30:70 v/v)
      containing trietylamine (0.5% v/v) and the products were detected by a porous
      graphite electrode set at an oxidation potential of +0.6 V. The linearity of
      response was examined for each derivatised compound and was analysed using
      solutions in the range 10-40 nmol/ml. The correlation coefficients of the linear
      regression of the standard curves were greater than 0.99. The method developed in
      this study was sensitive and very selective. Because of the specificity for
      primary phenylethylamines, it could be applicable for the assay of other related
      substances in toxicology and drugs abuse.

PMID- 12191708
TI  - Specific, sensitive and accurate LC-MS/MS method for the measurement of levovirin
      in rat and monkey plasma.
AB  - Levovirin is a guanosine nucleoside analogue and the L-enantiomer of ribavirin.
      Levovirin has a better safety profile than ribavirin, exerts similar
      immunomodulatory effects in a mouse efficacy model, and may provide a better
      therapeutic option than ribavirin in patients with chronic hepatitis C virus
      (HCV) infection. To facilitate pharmacokinetic studies, a LC-MS/MS method for the
      analysis of levovirin in rat and monkey plasma was developed and validated. The
      method involved adding ICN 10537 as an internal standard, protein precipitation
      with acetonitrile followed by separation on an Intersil Silica column, and
      quantification by a MS/MS system equipped with positive electrospray ionization
      (ESI) in the multiple reaction monitoring (MRM) mode. The MS/MS reaction was
      selected to monitor the 245-->113 and 259-->128 transitions for levovirin and
      internal standard, respectively. The calibration curve was linear over a
      concentration range of 10-5000 ng/ml. The limit of quantitation was 10 ng/ml, the
      coefficient of variation (CV) was 3-5%, and the bias was 3-6%. Intra- and inter
      day analysis of QC samples at 30, 1500 and 3500 ng/ml indicated that the method
      was precise (CV<6%) and accurate (bias <9%). Levovirin in rat and monkey plasma
      was stable at 5 degrees C for at least 24 h, 0 degrees C for at least 4 h, and
      after three freeze-thaw cycles. This specific, accurate and precise assay is
      useful in the study the pharmacokinetic characteristics of this compound.

PMID- 12191710
TI  - Polarographic determination of benzaldehyde in benzyl alcohol and sodium
      diclofenac injection formulations.
AB  - A rapid and sensitive polarographic method was developed for qualitative as well
      as quantitative analysis of the neurotoxic contaminant benzaldehyde in Na
      diclofenac injections and in benzyl alcohol used for parental formulations. A
      well-defined differential pulse (DP) polarographic peak or a sampled direct
      current (SDC) wave was obtained at -1.39 V (vs. silver-silver chloride reference
      electrode) in Britton-Robinson buffer (pH 9.15) and at -1.41 V in 0.1 M LiCl
      solution. The reduction step involves a two-electron process, corresponding to
      the formation of benzyl alcohol. No peaks were observed in the anodic branch of
      the cyclic voltammogram, emphasizing the occurrence of an irreversible process.
      The peak current versus concentration relationship was found to be linear up to
      50 microg/ml with the detection limit of 10 ng/ml and quantitation limit of 30
      ng/ml. The relative standard deviations (S.D.) obtained for concentration levels
      of benzaldehyde as low as 25 microg/ml with the SDC and DP methods were 1.5 and
      0.78% (n=10), respectively. Benzyl alcohol and Na-diclofenac are not
      electrochemically active, and metabisulfite reductions at -0.664 and -1.240 V do
      not interfere with the benzaldehyde reduction peak. The proposed methods (DP and
      SDC polarography) have been applied satisfactorily to the determination of
      benzaldehyde traces in benzyl alcohol and in different pharmaceutical products
      such as Na-diclofenac injectable formulations.

PMID- 12191711
TI  - Polyoxyethylene-Delta(9,11)-didehydrostearate and glycerol-polyoxyethylene
      Delta(9,11)-didehydrostearate: two new components of the non-ionic emulsifier
      Cremophor EL.
AB  - The polyethoxylated heterogeneous components of the so far poorly characterised
      non-ionic emulsifier Cremophor EL (polyoxyl 35 castor oil) (CrEL) were
      fractionated by cyclodextrin modified micellar electrokinetic capillary
      chromatography (CD-MEKC) combined with indirect UV detection. The resulting peaks
      were assigned to the corresponding components by delayed extraction matrix
      assisted laser desorption/ionization time of flight mass spectrometry (DE-MALDI
      TOF-MS) as detection device. In order to combine CE and MS the fractionating
      robot Probot was employed which enables both the online fractionation of the CE
      eluate on a MALDI target during the electrophoretic separation and the
      simultaneous dosage of the MALDI matrix. The obtained mass spectra were evaluated
      by comparing the residue masses of the homologue peak series of the
      polyethoxylates with the calculated residue masses of potential CrEL-components.
      The overlapping of homologue peak series with isobaric residue masses was
      detected by using the residue mass plot, the newly developed evaluation method.
      Combining theses techniques, both the first detailed structure elucidation and a
      semiquantitative analysis of the polyethoxylated CrEL-components was achieved.
      Together with the polyethoxylate series of yet elucidated structures two
      additional series were observed the corresponding components of which could not
      be identified at the beginning. Systematic investigations showed that the
      elimination of water from ricinoleic acid during the synthesis of the emulsifier
      leads to the polyethoxylates glycerol POE-Delta(9,11)-didehydrostearate and POE
      Delta(9,11)-didehydrostearate so far unknown in CrEL.

PMID- 12191712
TI  - A RP-LC method with evaporative light scattering detection for the assay of
      simethicone in pharmaceutical formulations.
AB  - A reversed-phase liquid chromatographic method has been developed and validated
      for the determination of the polydimethylsiloxane (PDMS) component of
      Simethicone, which is used as an anti-foaming agent in pharmaceutical
      formulations. The method involves acidification to neutralise antacid components
      of the formulation, then a single extraction of the PDMS with dichloromethane.
      This is followed by separation with a reversed-phase column using an acetonitrile
      chloroform solvent gradient, and quantification by an evaporative light
      scattering detector. An assay precision of 3% was achieved in intraday and
      interday determinations. No interference was found from the aluminium and
      magnesium hydroxide components of antacid formulations.

PMID- 12191713
TI  - Voltammetric determination of fenbendazole in veterinarian formulations.
AB  - A versatile voltammetric method for quantitative determination of fenbendazole
      (FBZ) in commercial tablets has been proposed, where direct dissolution of
      tablets is carried out in 0.1 mol l(-1) tetrabutylamoniun tetrafluorborate
      containing dimethylformamide solutions. Linear sweep (LSV), square wave (SWV) and
      differential pulse (DPV) voltammetry techniques were applied to study FBZ at a
      glassy carbon electrode, exhibiting a well defined irreversible oxidation peak at
      1.15 V vs. SCE. This methodology allows a precise quantitative determination of
      FBZ presenting detection limits of 5.2 x 10(-5) (LSV), 5.0 x 10(-6) (DPV) and 5.0
      x 10(-5) mol l(-1) (SWV).

PMID- 12191714
TI  - Development and validation of an LC assay for sumatriptan succinate residues on
      surfaces in the manufacture of pharmaceuticals.
AB  - A high performance liquid chromatographic (HPLC) method for the assay of
      sumatriptan succinate residues in swabs collected from manufacturing equipment
      surfaces was developed and validated in order to control a cleaning procedure.
      The swabbing procedure using two cotton swabs moistened with water was validated
      applying a wipe-test and a HPLC method developed to determine low quantities of
      the drug. The HPLC method involves a C18 column at 25 degrees C, a mixture of
      ammonium phosphate monobasic (0.05 M)-acetonitrile (84:16, v/v) as a mobile phase
      and UV detection at 228 nm. Using the proposed method, the average recoveries
      obtained are of 88.5% for vinyl, 94.2% for glass and 95.2% for stainless steel
      plates with RSD of 5.5 (n=36), 2.3 (n=36), 2.2% (n=36), respectively. The method
      was successfully applied to the assay of real swab samples collected from the
      equipment surfaces.

PMID- 12191715
TI  - Chiral separation of pemoline enantiomers by cyclodextrin-modified micellar
      capillary chromatography.
AB  - Micellar electrokinetic chromatography (MEKC) was successfully applied to the
      chiral separation with the addition of cyclodextrins (CDs) as chiral selector to
      running buffer. Chiral separation depended on the type of CDs. Mono-3-O
      phenylcarbamoyl-beta-CD was effective for the chiral separation of pemoline. We
      investigated the type and concentration of CD and other parameters such as buffer
      pH, the concentration of SDS and the effect of organic modifier. The conditions
      for enantiomeric separation of pemoline were as follows: 40 mmol/l borate buffer
      at pH 9.0 with 40 mmol/l SDS, 20 mmol/l mono-3-O-phenylcarbamoyl-beta-CD and 10%
      2-propanol. Baseline separation (Rs=2.21) of pemoline can be achieved.

PMID- 12191716
TI  - Highly sensitive liquid chromatography-tandem mass spectrometry method for
      quantification of a new bone anabolic agent, TAK-778, in human serum.
AB  - A liquid chromatography-tandem mass spectrometric (LC-MS-MS) method for the
      highly sensitive determination of a new bone-anabolic agent, TAK-778 in human
      serum was developed. The internal standard (I.S.) used was deuterated TAK-778.
      TAK-778 and I.S. were extracted from serum samples with diethyl ether at neutral
      pH. A turbo ion spray interface was used as the ion source of LC-MS-MS, and the
      analysis was performed in the selected reaction monitoring mode. The lower limit
      of quantification was 0.02 ng/ml when 0.4 ml of serum was used, and the standard
      curve was linear in the range of 0.02-10 ng/ml. The method was precise; the intra
      and inter-day precision of the method was not more than 17.9%. The accuracy of
      the method was good with the deviations between added and calculated
      concentration of TAK-778 being typically within 9.0%.

PMID- 12191717
TI  - Verapamil drug metabolism studies by automated in-tube solid phase
      microextraction.
AB  - Verapamil is a common calcium antagonist described with antianginal,
      antihypertensive and antiarrythmic properties. The metabolites of verapamil have
      also shown pharmacological properties and therefore sample preparation and
      analysis techniques capable of metabolic screening for verapamil are important.
      In-tube SPME is a relatively new method integrating sample extraction,
      concentration and introduction into one single step without the use of organic
      solvents. The capability of in-tube SPME in bioanalysis has been reviewed but
      there has been no application described in the field of drug metabolism. Since
      automation and interfacing of in-tube SPME coupled to liquid chromatography-mass
      spectrometry (LC-MS) is possible, we confirm in this study that it is a powerful
      method to monitor the main metabolites of verapamil in various biological
      matrices like plasma, urine and cell culture media. Further, we show that it
      could also be used in routine pharmacokinetics measurements. An in-tube SPME LC
      MS method was developed to extract and analyze the metabolic profile of verapamil
      from biological matrices. The detection limit for verapamil, gallopamil,
      norverapamil and PR22 were 52, 53, 65 and 83 ng/ml (UV detection) and 5, 6, 6 and
      8 ng/ml (MS detection), respectively. The precision of the method was calculated
      in various biological matrices and the average % R.S.D. (N=5) for verapamil,
      gallopamil, norverapamil and PR22 was 3.9, 3.7, 3.8 and 4.3% (MS detection),
      respectively. The linear dynamic range was determined to be 100-800 ng/ml (UV
      detection) with a total sample preparation and analysis time of 34 min.

PMID- 12191718
TI  - NMR spectroscopy: a useful tool for characterisation of plant extracts, the case
      of supercritical CO2 arnica extract.
AB  - The efficiency of two-dimensional homonuclear (1)H-(1)H correlated spectroscopy
      (COSY) and two-dimensional reverse heteronuclear shift correlation spectroscopy
      (i.e. heteronuclear multiple quantum correlation, HMQC) in characterising the
      content of the constituents of innovative extracts is demonstrated. These
      experiments were performed directly on a supercritical carbon dioxide (CO(2))
      commercial extract of arnica and were able to fully characterise the active
      constituents, sesquiterpenes, and other metabolites extracted with the
      supercritical CO(2), namely polyketides. Identification of constituents was
      performed by combining literature data and information obtained by 2D-NMR
      experiments.

PMID- 12191720
TI  - Separation of tricyclic antidepressants by capillary zone electrophoresis with
      N,N,N',N'-tetramethyl-1,3-butanediamine (TMBD) as an effective electrolyte
      additive.
AB  - Five tricyclic antidepressants (TADs), desipramyne, nortriptyline, imipramine,
      doxepin and amitriptyline, were separated by using the N,N,N',N'-tetramethyl-1,3
      butanediamine (TMBD) as additive in the background electrolyte solution. Because
      the tricyclic antidepressants are similar in structure, mass and pka values,
      their separation, by capillary zone electrophoresis, requires the careful
      manipulation of parameters, such as the pH and the composition of the electrolyte
      solution. As basic drugs, the TADs interact with the silanol groups on the
      capillary wall giving rise to peak broadening and asymmetry, non reproducible
      migration times and failing in selectivity. Different concentrations of TMBD (40,
      60, 100 and 150 mM) were used at pH 9.5, but only a 100 mM TMBD allowed a good
      separation and a high efficiency for all the TADs. At this pH the separation was
      not possible without additive. This result is due to the reduced electroosmotic
      flow whose mobility is at a value of 10(-9) m(2) V(-1) s(-1).

PMID- 12191721
TI  - Validation of a LC method for the analysis of phenolic compounds from aqueous
      extract of Phyllanthus niruri aerial parts.
AB  - A reversed-phase high-performance liquid chromatographic separation and
      quantitative method using a phosphoric acid-acetonitrile gradient was developed
      to analyze phenolic compounds present in aqueous extract from the aerial parts of
      Phyllanthus niruri. The chromatographic method was validated for linearity,
      precision and accuracy for both reference substance (gallic acid) and for three
      well resolved peaks from P. niruri aqueous extract. Both calibration curves were
      linear with correlation coefficients higher than 0.999. The reproducibility for
      the three peaks ranged from 2.3% to 4.6% and the accuracy for gallic acid in the
      aqueous extract was 103%. The method allowed the complete resolution of three
      peaks, one of them was identified by diode array detection as gallic acid. The
      analysis of the botanic morphological elements of the aerial parts from P. niruri
      showed that the leaves have a higher amount of phenolic compounds than the
      branches.

PMID- 12191719
TI  - Renal excretion profiles of psilocin following oral administration of psilocybin:
      a controlled study in man.
AB  - In a clinical study eight volunteers received psilocybin (PY) in psychoactive
      oral doses of 212+/-25 microg/kg body weight. To investigate the elimination
      kinetics of psilocin (PI), the first metabolite of PY, urine was collected for 24
      h and PI concentrations were determined by high-performance liquid chromatography
      with column switching and electrochemical detection (HPLC-ECD). Sample workup
      included protection of the unstable PI with ascorbic acid, freeze-drying, and
      extraction with methanol. Peak PI concentrations up to 870 microg/l were measured
      in urine samples from the 2-4 h collection interval. The PI excretion rate in
      this period was 55.5+/-33.8 microg/h. The limit of quantitation (10 microg/L) was
      usually reached 24 h after drug administration. Within 24 h, 3.4+/-0.9% of the
      applied dose of PY was excreted as free PI. Addition of beta-glucuronidase to
      urine samples and incubation for 5 h at 40 degrees C led to twofold higher PI
      concentrations, although 18+/-7% of the amount of unconjugated PI was decomposed
      during incubation. We conclude that in humans PI is partially excreted as PI-O
      glucuronide and that enzymatic hydrolysis extends the time of detectability for
      PI in urine samples.

PMID- 12191722
TI  - Two derivative spectrophotometric determinations of indapamide in pharmaceutical
      dosage forms.
AB  - Simple, fast and reliable derivative spectrophotometric methods were developed
      for determination of indapamide in bulk and pharmaceutical dosage forms. The
      solutions of standard and the sample were prepared in methanol. The quantitative
      determination of the drug was carried out using the first-derivative values
      measured at 252.8 nm (N=6) and the second-derivative values measured at 260.4 nm
      (N=9). Calibration graphs constructed at their wavelengths of determination were
      linear in the concentration range of indapamide using peak to zero 1.00-30.00
      microg ml(-1) for first-derivative and 1.00-35.00 microg ml(-1) for second
      derivative spectrophotometric method. The developed methods were successfully
      applied for the assay of pharmaceutical dosage forms which do not require any
      preliminary separation or treatment of the samples. The details of the
      statistical treatment of analytical data are also presented. The results obtained
      from two derivative spectrophotometry were compared with a spectrophotometric
      method reported in literature and no significant difference was found
      statistically.

PMID- 12191723
TI  - Simultaneous detection of hippuric acid and methylhippuric acid in urine by
      Empore disk and gas chromatography-mass spectrometry.
AB  - A method is described for the determination of hippuric acid (HA) and o-, m-, and
      p-methylhippuric acids (o-, m-, p-MHAs) in urine using solid-phase extraction and
      gas chromatography-mass spectrometry (GC-MS). The extraction procedure uses an
      Empore disk, derivatized into the respective trimethyl silyl derivatives. All
      metabolites including the internal standard (I.S.) were clearly able to be
      analyzed by the DB-17 column. The calibration curves for the four acids show
      linearity in the range of 5-70 microg/ml. The detection limit of each acid was
      1.0-2.5 microg/ml.

PMID- 12191724
TI  - Comparison of UV- and second derivative-spectrophotometric and LC methods for the
      determination of valsartan in pharmaceutical formulation.
AB  - UV- and second derivative-spectrophotometric and high-performance liquid
      chromatographic methods for the determination of valsartan in pharmaceutical
      formulation have been developed. For the first method, UV-spectrophotometry,
      standard solutions were measured at 205.6 nm. The linearity changes were found to
      be 2.0-10.0 microg ml(-1) in ethanol and the regression equation was A=1.05 x 10(
      1)C+4.26 x 10(-2) (r=0.9997). For the second method, the distances between two
      extremum values (peak-to-peak amplitudes), 221.6 and 231.2 nm were measured in
      the second order derivative-spectra of standard solutions. Calibration curves
      were constructed by plotting d(2)A/dlambda(2) values against concentrations, 0.5
      4.0 microg ml(-1) of valsartan standards in ethanol. Regression equation of
      linear calibration graph was calculated as D=2.9 x 10(-2)C-2.37 x 10(-3)
      (r=0.9996). The third method was based on high-performance liquid chromatography
      on C18 column using acetonitrile, phosphate buffer as a mobile phase and losartan
      as internal standard. Detection was carried out at 265 nm with a UV-detector. The
      assay was linear over the concentration range at 1.0-5.0 microg ml(-1) and
      regression equation was found to be A=2.74 x 10(-1)C+2.06 x 10(-2) (r=0.9991).
      Commercial capsules containing 160 mg valsartan were analysed by the developed
      methods and the results obtained were compared statistically at 95% confidence
      level.

PMID- 12191725
TI  - The superior olivary complex of the hamster has multiple periods of cholinergic
      neuron development.
AB  - Cholinergic neurons of the superior olivary complex share a common embryological
      and phylogenetic origin with brainstem motor neurons and serve as the major
      descending efferent pathway either to the cochlea as part of the olivocochlear
      system or to the cochlear nucleus. In this study, we investigated the
      developmental expression patterns of choline acetyltransferase (ChAT) and its co
      localization with calcitonin gene-related peptide within the superior olivary
      complex and neighboring brainstem motor nuclei. At embryonic day 12, neurons in
      the ventral nucleus of the trapezoid body were first to express ChAT. The
      temporal expression pattern of both ChAT mRNA and immunoreactivity in this
      periolivary region mimicked motor neurons in the facial and trigeminal motor
      nuclei. Just before birth, shell neurons surrounding the lateral superior olive
      expressed ChAT. Neither ChAT-positive periolivary neurons nor shell neurons co
      expressed calcitonin gene-related peptide during development or in the adult.
      Immediately following birth, intrinsic neurons within the lateral superior olive
      expressed ChAT but not calcitonin gene-related peptide. However, a transient
      increase in the number of ChAT-positive neurons in the lateral superior olive
      coincided with the onset of the calcitonin gene-related peptide co-expression
      within these neurons. We conclude that ChAT expression appears first in
      periolivary regions containing medial olivocochlear neurons, precedes the
      expression of calcitonin gene-related peptide in the superior olivary complex,
      and is co-expressed with calcitonin gene-related peptide within the lateral
      superior olive containing lateral olivocochlear neurons. These data suggest that
      the lateral olivocochlear system co-expresses ChAT and calcitonin gene-related
      peptide, whereas the medial olivocochlear system does not.

PMID- 12191726
TI  - Neurons possessing enzymes of dopamine synthesis in the mediobasal hypothalamus
      of rats. Topographic relations and axonal projections to the median eminence in
      ontogenesis.
AB  - We evaluated the topographic relations between tyrosine hydroxylase (TH)- and/or
      aromatic L-amino acid decarboxylase (AADC)-immunoreactive neurons in the arcuate
      nucleus (AN), as well as between TH- and/or AADC-immunoreactive axons in the
      median eminence (ME) in rats at the 21st embryonic day, 9th postnatal day, and in
      adulthood. The double-immunofluorescent technique in combination with confocal
      microscopy was used. Occasional bienzymatic neurons but numerous monoenzymatic TH
      or AADC-immunoreactive neurons were observed in fetuses. There was almost no
      overlap in the distribution of monoenzymatic neurons, and therefore few
      appositions were observed in between. In postnatal animals, numerous bienzymatic
      neurons appeared in addition to monoenzymatic neurons. They were distributed
      throughout the AN resulting in the increased frequency of appositions.
      Furthermore, specialized-like contacts between monoenzymatic TH- and AADC
      immunoreactive neurons appeared. The quantification of the fibers in the ME
      showed that there were large specific areas of the monoenzymatic TH
      immunoreactive fibers and bienzymatic fibers in fetuses, followed by the gradual
      reduction of the former and the increase of the latter to adulthood. The specific
      area of the monoenzymatic AADC-immunoreactive fibers in fetuses was rather low,
      and thereafter increased progressively to adulthood. The fibers of all the types
      were in apposition in the ME at each studied age. Close topographic relations
      between the neurons containing individual complementary enzymes of dopamine
      synthesis at the level of cell bodies and axons suggest functional interaction in
      between.

PMID- 12191727
TI  - Galanin receptor over-expression within the amygdala in early Alzheimer's
      disease: an in vitro autoradiographic analysis.
AB  - Galanin receptor (GALR) expression is increased in various areas of the limbic
      system in end stage Alzheimer's disease (AD). The amygdaloid complex is a key
      component of the limbic circuit, is involved in homeostatic and cognitive
      functions, is impacted in AD and contains the peptide and receptor for galanin.
      Although GALR expression occurs in the amygdala in end stage AD, it remains to be
      determined whether a plasticity response occurs early or late in the disease.
      Therefore, we analyzed the distribution and associated changes in GALR binding in
      the amygdala during the progression of AD using an in vitro receptor
      autoradiographic method. Human galanin ([125I]hGAL) receptor binding was
      performed on brain sections from early and late AD cases, as well as normal age
      matched control subjects. In aged controls, densities of [125I]hGAL binding sites
      were found in the central and the corticomedial nuclei. Relative to controls,
      possible/early AD cases displayed significantly greater numbers of [125I]hGAL
      binding sites in the central nucleus and cortico-amygdaloid transition area. In
      contrast, we found a decrease in the number of binding sites for [125I]hGAL in
      late as compared to early AD cases. The over-expression of GALRs in subfields of
      the amygdaloid early in AD suggests that galaninergic systems play a key role in
      limbic related behavioral changes during the disease process.

PMID- 12191728
TI  - Immunocytochemical evidence for the striatal nature of the rat lateral part of
      interstitial nucleus of the posterior limb of the anterior commissure (IPAC).
AB  - The present study focuses on the basal forebrain region originally designated as
      fundus striati, but currently known as 'interstitial nucleus of the posterior
      limb of the anterior commissure' (IPAC). Using multiple immunofluorescence of the
      calcium-binding proteins parvalbumin and calbindin, the GABA(A) receptor alpha1
      subunit, vasoactive intestinal polypeptide (VIP), met(5)-enkephalin (MENK) and
      glutamic acid decarboxylase (GAD), it was shown that VIP-immunostained axons,
      which are typical for major parts of the extended amygdala, densely innervate
      only the medial part of IPAC, while they are absent in the lateral part. On the
      other hand, large-sized GABAergic, parvalbumin- and GABA(A) receptor alpha1
      subunit-immunoreactive neurons, which are densely covered by separate GAD- and
      MENK-immuno reactive terminals and a type of medium-sized alpha1-subunit
      monolabelled cells, occur in the dorsal striatum and in the adjacent lateral part
      of IPAC as well. Large-sized neurons double labelled for parvalbumin and the
      GABA(A) receptor alpha1-subunit are also widely distributed in the neighbouring
      ventral pallidum. Neurons of this type are absent, however, in the medial part of
      IPAC and other extended amygdala subunits. Our findings confirm the recent
      suggestion of a morphofunctional dichotomy of IPAC (Comp. Neurol. 439 (2001)
      104), as only the medial part reveals characteristics as typical for extended
      amygdala, while its lateral part exhibits cytochemical peculiarities of striatal
      tissue. Therefore, the term 'lateral part of IPAC' should be replaced by the term
      'putaminal fundus (fundus putaminis)' according to recently published
      designations of corresponding striatal constituents (Atlas of the Human Brain,
      2002, Academic Press, San Diego, CA; J. Chem. Neuroanat. 23 (2002) 75).

PMID- 12191729
TI  - Effect of prenatal sound stimulation on medio-rostral neostriatum/hyperstriatum
      ventrale region of chick forebrain: a morphometric and immunohistochemical study.
AB  - The higher auditory association area in chick forebrain, i.e. medio-rostral
      neostriatum/hyperstriatum ventrale region (MNH), is involved in juvenile auditory
      filial imprinting. Studies show that neuronal size as well as expression of
      calcium-binding proteins, parvalbumin (PV) and calbindin D28K (CaBP) are
      regulated by neuronal activation. In the present study, we have determined the
      effect of extra auditory stimulation, given as a prenatal sound enrichment
      protocol, on MNH neurons of posthatch day 1 chicks. Patterned species-specific or
      musical (sitar) sounds were provided in a graded manner from embryonic day 10
      through hatching. Thionin and immunohistochemically stained (PV and CaBP) neurons
      were evaluated by morphometric methods. The thionin-stained MNH neurons of both
      the auditory stimulated groups showed a significant increase in nuclear area
      compared to controls. The change in nuclear dimension was greater in the music
      stimulated than in the species-specific sounds-stimulated group. These
      observations indicate a positive influence of prenatal sound stimulation on MNH
      neurons. The auditory stimulated groups also demonstrated an increase in the
      proportion of PV- and CaBP-neurons compared to controls, with the species
      specific sounds-stimulated group showing a significantly higher percentage of
      immunostained cells than the music-stimulated group. However, immunostained cells
      of both the auditory stimulated groups did not show a significant change in size.
      These cytoplasmic proteins, by acting as intracellular buffers, enable neurons to
      display high electrical activity without calcium overload. The influx of Ca(2+)
      ions is essential for long-term potentiation, a phenomenon important for learning
      and memory. The increase in percentage of the neurons containing calcium-binding
      proteins may provide a morphological basis for enhancement of auditory imprinting
      and learning.

PMID- 12191730
TI  - Nestin immunoreactivity in local neurons of the adult rat striatum after remote
      cortical injury.
AB  - Nestin is a marker for the neuronal and glial precursor cells and is expressed in
      reactive astrocytes after brain injury. Following restricted neocortical injury,
      we found that cells with neuronal morphology in the adult rat striatum became
      immunoreactive for both nestin and the neuronal marker, microtubule-associated
      protein 2 (MAP-2), but not for the astroglial marker, glial fibrillary acidic
      protein (GFAP). The number of nestin-positive cells transiently increased in the
      striatum. Continuous administration of 5-bromo-2'-deoxyuridine (BrdU) after
      cortical injury did not reveal any newly generated neurons in the striatum.
      Double-labeling fluorescent immunocytochemistry revealed that the nestin-positive
      striatal cells were also substance-P-positive. These findings suggest that some
      factors released from the injured cortex may induce nestin immunoreactivity in
      striatal neurons.

PMID- 12191731
TI  - Changes in mRNA for VAMPs following facial nerve transection.
AB  - Vesicle-associated membrane proteins (VAMPs) are involved in synaptic vesicle
      recycling and exocytosis in neurons. Here we report the changes in mRNA
      expression for VAMPs (VAMP1, -2 and -3) in the facial motor nucleus of adult rats
      following axotomy by in situ hybridization. Signals for VAMP2 and -3 mRNAs in the
      facial nucleus were increased from 3 to 28 days after axotomy. On the contrary,
      VAMP1 mRNA, which was abundantly expressed in the control facial nucleus, was
      transiently decreased from 3 to 21 days after axotomy. Differential regulation of
      VAMPs may reflect distinct roles in nerve regeneration.

PMID- 12191733
TI  - Highlights of contemporary issues in the medical management of prostate cancer.
AB  - This paper highlights contemporary issues in the medical management of prostate
      cancer. Controversies surrounding adjuvant and neo-adjuvant hormonal therapy in
      localized prostate cancer are reviewed, as well as the use of chemohormonal
      therapy in high risk localized disease. The latent period of asymptomatic
      biochemical progression prior to clinical progression is an opportunity to
      evaluate new non-toxic therapies. In patients with advanced metastatic disease
      hormonal therapy and new alternatives are discussed. Chemotherapy in hormone
      refractory prostate cancer (HRPC) is extensively covered as well as the emerging
      role of molecular-targeted therapies.

PMID- 12191734
TI  - Laparoscopic radical prostatectomy: assessment after 550 procedures.
AB  - PURPOSE: To evaluate our experience in laparoscopic radical prostatectomy.
      MATERIALS AND METHODS: Between January 1998 and December 2000, 550 consecutive
      patients eligible for radical prostatectomy, were operated laparoscopically. Data
      concerning surgery and post-operative course were assessed and recorded.
      Oncological data were assessed by pathological examination and post-operative PSA
      level. Functional results were assessed with a self-questionnaire. RESULTS: The
      mean operating time was 170 min for the last 350 patients. Surgical conversion
      was necessary in seven patients (1.3%). Mean intra-operative bleeding was 290 ml
      (range: 50-1500 ml) for the last 350 patients. The overall transfusion rate was
      5.27%. Mean bladder catheterization time was 4.2 days and median postoperative
      stay was 5 days in the last 350 patients. By pathological stage, 4 pT2a specimens
      (3.3%), 48 pT2b specimens (15%), 21 pT3a specimens (33%), 19 pT3b specimens (47%)
      were found to have positive surgical margins. For pT2a and pT2b stages, non
      biological recurrence probability (PSA<0.1 ng/ml) is, respectively, 92.3% at 36
      months, and 86.3% at 31 months. The continence rate (no pad) was 82.3% at 12
      months among the 255 first patients. For 47 consecutive selected patients,
      spontaneous erection rate was 85 and 66% experienced spontaneous intercourse.
      CONCLUSIONS: Laparoscopic radical prostatectomy is currently feasible, with low
      perioperative morbidity. Taking into account the postoperative follow-up,
      oncological results are identical to those obtained with conventional surgery.
      The functional results are encouraging.

PMID- 12191735
TI  - Radical perineal prostatectomy: a model for evaluating local response of prostate
      therapy.
AB  - To establish a model for preoperative counseling and postoperative outcome in
      patients who choose radical perineal prostatectomy for the clinically localized
      prostatic malignancy, the following postulates have been identified: (1) the use
      of preoperative prostate specific antigen (PSA) and Gleason Sum at the time of
      biopsy can be used to segregate the outcome among patients with Gleason Sum 2
      through 6, 7, and 8 through 10. (2) Postoperative PSA levels are excellent
      surrogate endpoints for defining disease control. (3) The biology of the primary
      malignancy defines the interval of death after recurrence. A total of 1242 men
      with the median age of 65.2 years who had Stage cT 1-2 NOMO disease underwent
      radical perineal prostatectomy. The final pathologic specimen was characterized
      with regard to disease extent and Gleason Sum. Patients were followed at 2 weeks,
      2 months, and then at 6-month intervals for biochemical, physical, and
      radiographic evidence of disease recurrence. Outcome was evaluated by determining
      time to biochemical failure (PSA 0.5 ng/ml or greater) or cancer associated death
      (death with a detectable PSA independent of treatment). Median time to non-cancer
      death was 19.3 years. Median cancer-associated death endpoints were not reached
      by patients with organ confined disease. Results were 17.7 years for specimen
      confined disease and 12.7 years for margin positive disease. At 5 years, 8, 35,
      and 65% of patients with organ confined, specimen confined, or margin positive
      disease, respectively, had PSA failure. This served as an excellent surrogate
      endpoint, preceding cancer associated death by 5-12 years, depending on the
      biological aggressiveness predicted by Gleason Sum. When segregated by Gleason
      Sum 2 through 6, 7 or 8 through 10 at the time of biopsy, there was a distinct
      differentiation in survival among these Gleason Sum classifications according to
      the PSA at the time of biopsy. This study confirms our postulates and provides
      guidelines for preparing different therapies among institutions. It also
      emphasizes that enthusiasm for new treatments may be based on insufficient follow
      up. PSA is an excellent surrogate endpoint and it is valuable in segregating
      patients prior to therapeutic selection and predicting outcome.

PMID- 12191736
TI  - Quality of life following radical prostatectomy.
AB  - Radical prostatectomy is a procedure performed with increasing frequency in
      patients with localized prostate cancer. Although, the operative morbidity is
      considerably low, urinary incontinence and erectile dysfunction remain an
      important and persistent problem. Since several years the impact of radical
      prostatectomy on the quality of life (HRQOL) is investigated. However, there are
      only few prospective studies dealing with rather small groups of patients. These
      studies indicate that urinary and sexual function have major impact on HRQOL.
      Although, there is a steady improvement in urinary function and decrease in
      urinary bother only about 65% of the patients reach the baseline at the end of
      the first year. In spite of this almost 90% of patients reach baseline in all
      other HRQOL domains such as general health perception, physical and social
      function after a mean period of 5 months. The importance of sexual desire and
      erectile capacity decreases with age; being important in 75 and 84% of men at the
      5th decenium and 48 and 59% at the 6th decenium. After standard radical
      prostatectomy almost all of the patients are impotent. Applying so-called nerve
      sparing techniques erectile function may be preserved in careful selected
      patients. It is the common theme that preservation of the 'neurovascular bundles'
      equals a high rate, but still age depended postoperative potency; however
      difficulties in regaining urinary control may embarrass the patient to such an
      extent to withdraw from sexual activity. Furthermore, the change of sexual
      ability and quality may have impact on the partner who do not want to initiate
      sexual activity because of the possible failure. This may cause an increased
      level of emotional distance, which again is deleterious for sexual activities.
      Patients who are sexually active prior to surgery report major distress in case
      of postoperative erectile impotence, but even in case of maintained erectile
      capacity some patients are bothered by the sexual dysfunction. Sexual counselling
      and providing the optimal erectile aid is therefore very important. Psychological
      distress of spouses may be significantly greater than that of the patients;
      general cancer distress, treatment related worries, concerns on physical
      limitations and pain are the main reasons. However, it may well be that women are
      willing to report their problems more often than their partners who may have a
      grin-and-bear-it attitude. In spite of this caveate, it is important to include
      the patient's spouse into the discussions on therapy and associated morbidity
      early on. Since radical prostatectomy for localized prostate cancer is only one
      of the possible treatment options, the patient has to be informed about the
      incidence and various types of morbidity which is associated with treatment and
      their possible impact on HRQOL. Appropriate and honest counselling will have
      significant influence on the well being of the patient after completing therapy.

PMID- 12191737
TI  - Overview of international collaborative group prostate cancer trials.
AB  - Clinical trials in prostate cancer have gained increasing influence upon the
      practice of medicine. A survey was conducted of ongoing International
      Collaborative Group Phase III trials in localized disease, high risk and locally
      advanced disease, post prostatectomy, rising PSA, metastatic disease, hormone
      refractory prostate cancer, chemoprevention, and screening. International
      cooperation has the advantage of faster recruitment of patients in order to more
      quickly answer important scientific questions. True international collaboration
      can avoid duplication of efforts and promote mutual planning of trials. It is
      essential to treat patients with prostate cancer in the framework of clinical
      trials since there are still many unanswered questions.

PMID- 12191738
TI  - EORTC prostate cancer trials: what have we learnt?
AB  - The aims of the European Organization for Research and Treatment of Cancer-GU
      (EORTC-GU) Group are to improve the treatment of cancer related problems by
      carrying out multicenter, multinational and intercontinental Phases II and III
      trials and the dissemination of their results via workshops, congresses and
      symposia. The first studies in prostate cancer dealt with the use of
      chemotherapeutic agents in advanced tumours. Mitomycin C was the most active
      agent identified. We have learnt that the primary tumour should not be used for
      response assessment in advanced disease but that Quality of life (QoL) assessment
      consistently applied may be. In later studies QoL and PSA response were
      considered as the most important endpoints for Phase II trials in this disease.
      In patients with locally advanced or metastatic disease maximal androgen blockade
      (MAB), in different forms, has been studied. Conflicting outcomes have been
      observed, which could be explained by the inclusion of patients with different
      prognostic factors at entry in the studies. The anti-androgen monotherapy
      approach in patients with M+ disease with good prognostic factors has been shown
      to be feasible, side effects using a steroidal agent were higher compared with
      non-steroidal agents. The hormono-chemotherapy approach in patients with M+
      disease and poor prognostic factors at entry showed not to be of any benefit in
      terms of survival and also QoL was worse in these patients. Patients with locally
      advanced disease treated with external beam radiation therapy had a significant
      better survival if this treatment was combined with 3 years of hormonal therapy.
      The ongoing Phase III study in metastatic prostate cancer is comparing
      intermittent hormonal therapy and continuous treatment and in locally advanced
      prostate cancer a Phase III trial is testing the so-called step-up and step-down
      regimen.

PMID- 12191739
TI  - Relative advantages and disadvantages of radical perineal prostatectomy versus
      radical retropubic prostatectomy.
AB  - In recent years prostate cancer has become the predominant malignancy in men.
      With the introduction of prostate specific antigen (PSA) the disease can be
      diagnosed at an early stage, at which surgical therapy can be curative. In the
      past century, the retropubic and the perineal routes were established as
      alternatives of surgical access to the gland for clinically localized prostate
      cancer. The selection of the operative route is mostly decided individually on
      the basis of surgical training and experience. The revived interest in perineal
      radical prostatectomy is explained by the fact that this technique has been
      associated with low morbidity. The differences of both surgical approaches of
      radical prostatectomy are elucidated and compared regarding tumor control and
      short and long term complication rates. Taking these results into consideration,
      specific advantages and disadvantages of radical perineal prostatectomy are
      emphasized.

PMID- 12191740
TI  - Early atherosclerosis...what does it mean?

PMID- 12191741
TI  - Intracoronary brachytherapy for restenosis: an efficient technique in the
      struggle for survival?

PMID- 12191742
TI  - Optimization of ACE inhibitor therapy in heart failure.

PMID- 12191743
TI  - Home-based management of patients with chronic heart failure--focus on content
      not just form!

PMID- 12191744
TI  - Un bout de souffle: ventilatory support for pulmonary oedema.

PMID- 12191745
TI  - Increased carotid intima-media thickness in children-adolescents, and young
      adults with a parental history of premature myocardial infarction.
AB  - AIMS: The present study was designed to test whether early carotid structural
      changes are demonstrable (by high resolution B-mode ultrasound) in children,
      adolescents and young adults with a history of premature parental myocardial
      infarction. METHODS AND RESULTS: One hundred and fourteen healthy young (5 to 30
      years) subjects with a parental history of premature myocardial infarction and
      114 age- and sex-matched control subjects were enrolled in the study. They were
      divided into two age groups: children and adolescents (age 5 to 18 years) (54
      individuals with a parental history of premature myocardial infarction and their
      control subjects; mean age 12.8+/-3.8 years) and young adults (age 19 to 30
      years) (60 individuals with a parental history and their controls; mean age
      23.8+/-3.3 years). All subjects underwent high resolution B-mode ultrasonographic
      evaluation of common carotid artery intima-media thickness. Lipid profile,
      resting blood pressure, body mass index and smoking status were also evaluated.
      In both age groups, compared to controls, subjects with a parental history of
      premature myocardial infarction had increased intima-media thickness of common
      carotid arteries (mean of combined sites: age 5-18 years: 0.45+/-0.076 mm vs
      0.40+/-0.066 mm in controls, P=0.008; age 19-30 years: 0.48+/-0.077 mm vs 0.45+/
      0.078 mm in controls,P =0.007) Offspring of coronary patients showed an
      unfavourable lipid profile, however, the association between a parental history
      of premature myocardial infarction and carotid intima-media thickness was
      independent of lipids, apolipoproteins and other traditional risk factors.
      CONCLUSIONS: Vascular structural changes associated with a parental history of
      premature myocardial infarction are already detectable in childhood and
      adolescence and occur independently of several traditional cardiovascular risk
      factors.

PMID- 12191746
TI  - Intracoronary beta-radiation to reduce restenosis after balloon angioplasty and
      stenting; the Beta Radiation In Europe (BRIE) study.
AB  - AIMS: The BRIE trial is a registry evaluating the safety and performance of
      (90)Sr delivered locally (Beta-Cath TM system of Novoste) to de-novo and
      restenotic lesions in patients with up to two discrete lesions in different
      vessels. METHODS AND RESULTS: In total, 149 patients (175 lesions) were enrolled;
      62 treated with balloons and 113 with stents. The restenosis rate, the minimal
      luminal diameter and the late loss were determined in three regions of interest:
      (a) in a subsegment of 5mm containing the original minimal luminal diameter pre
      intervention termed target segment; (b) the irradiated segment, 28 mm in length,
      and (c) the entire analysed segment, 42 mm in length, termed the vessel segment.
      Binary restenosis was 9.9% for the target segment, 28.9% for the irradiated
      segment, and 33.6% for the vessel segment. These angiographic results include
      5.3% total occlusions. Excluding total occlusions binary restenosis was 4.9%, 25%
      and 29.9%, respectively. At 1 year the incidence of major adverse cardiac events
      placed in a hierarchical ranking were: death 2%, myocardial infarction 10.1%,
      CABG 2%, and target vessel revascularization 20.1%. The event-free survival rate
      was 65.8%. Non-appropriate coverage of the injured segment by the radioactive
      source termed geographical miss affected 67.9% of the vessels, and increased edge
      restenosis significantly (16.3% vs 4.3%, P=0.004). It accounted for 40% of the
      treatment failures. CONCLUSION: The results of this registry reflect the learning
      process of the practitioner. The full therapeutic potential of this new
      technology is reflected by the restenosis rate at the site of the target segment.
      It can only be unravelled once the incidence of late vessel occlusion and
      geographical miss has been eliminated by the prolonged use of thienopyridine, the
      appropriate training of the operator applying this new treatment for restenosis
      prevention, and the use of longer sources.

PMID- 12191747
TI  - A mechanistic investigation of ACE inhibitor dose effects on aerobic exercise
      capacity in heart failure patients.
AB  - BACKGROUND: Angiotensin converting enzyme inhibitors at high doses have been
      shown to improve prognosis of heart failure patients. Their beneficial effects on
      exercise capacity have been less convincing in large parallel group studies. The
      objective of this investigation was to explore the mechanisms involved in dose
      related functional effects and to test the hypothesis that a trial recommended
      high dose of lisinopril would improve aerobic exercise capacity and
      cardiovascular function more than with a low dose. METHODS: Twelve patients with
      symptomatic heart failure completed a randomized double-blind crossover trial of
      lisinopril 5 mg o.d. and 20 mg o.d. for 24 weeks, crossing over the doses at 12
      weeks. The primary end-point was aerobic exercise capacity, and the secondary end
      points were cardiac performance at peak exercise and dobutamine stimulation.
      RESULTS: The aerobic exercise capacity (primary end-point) was significantly
      higher during the 5mg per day dosage compared to the 20 mg (1696 vs 1578 ml.min(
      1), P=0.016), equivalent to a rise of 1.53 ml.kg(-1)min(-1) from the 19.6 ml.kg(
      1)min(-1) with 20mg when normalized by body weight. Seventy-three percent of
      patients showed greater peak oxygen consumption and peak cardiac power output
      with the 5mg per day dose than the 20 mg, and none showed the opposite. In terms
      of cardiac performance, although the results were not statistically significant,
      there was a consistent pattern showing the same directional changes in favour of
      the lower dose in peak exercise cardiac power output and cardiac power output at
      maximal dobutamine. There were no significant differences in the resting values.
      A total of 24 adverse reactions were reported during the 5 mg phase compared to
      38 during the 20 mg phase. CONCLUSIONS: Contrary to expectation, the aerobic
      exercise capacity of patients was found to be greater with the lower dose of
      lisinopril, suggesting that therapy with ACE inhibitors for heart failure may
      require tailoring the doses to the individual to optimize functional benefits in
      relation to the assumed prognostic benefits.

PMID- 12191748
TI  - An economic analysis of specialist heart failure nurse management in the UK; can
      we afford not to implement it?
AB  - AIMS: Hospital activity represents the major component of health care expenditure
      related to heart failure. This study evaluated the economic impact of applying
      specialist nurse management programmes that limit heart failure-related hospital
      readmissions within a whole population. METHODS: Using a reliable and validated
      estimate of the current level and cost of heart failure-related hospital activity
      in the U.K., we determined the thresholds at which the actual cost of
      establishing and applying a national service based on three different models of
      specialist nurse management would be equal to the 'cost' of bed utilization
      associated with preventable hospital readmissions in the year 2000. The three
      models of care examined were home-based, clinic-based or a combination of home
      plus clinic-based, post-discharge follow-up. The potential impact of this service
      was based on a U.K.-wide caseload of 122,000 patients discharged to home with a
      discharge diagnosis of congestive heart failure in that year. RESULTS: Based on
      heart failure-specific patterns of hospital activity, we estimate that 47,000 of
      these 122,000 patients would normally accumulate a total of 594000 days of
      associated hospital stay from 49,000 readmissions (for any reason) within 1 year
      of hospital discharge. The cost of these admissions to the National Health
      Service was calculated at 166.2 million pounds sterling. Taking into account
      other costs associated with such hospital activity (e.g. general practice and
      hospital outpatient visits) each 10% reduction in recurrent bed utilization would
      be associated with 18.0 million ponds sterling in cost savings. Alternatively,
      the cost of applying a U.K.-wide programme of home-, clinic- or home plus clinic
      based follow-up was calculated to be 69.4 pounds sterling, 73.1 pounds sterling
      and 72.5 million pounds sterling per annum, respectively. The relative thresholds
      at which generated 'cost-savings' would equal the cost of applying these
      programmes of care would therefore be a 38.5%, 40.6% and 40.3% reduction in
      recurrent bed utilization, respectively. If, as expected, a home-based programme
      of specialist nurse management reduced recurrent bed utilization by 50% or more,
      annual savings equivalent to 169,000 pounds sterling per 1000 patients treated
      would be generated. CONCLUSIONS: This is the first study to examine the economic
      consequences of applying a specialist nurse-mediated, post-discharge management
      service for heart failure within a whole population. Our findings suggest that
      such a service will not only improve quality of life and reduce readmissions in
      patients with congestive heart failure, but also reduce costs and improve the
      efficiency of the health care system in doing so.

PMID- 12191749
TI  - Randomised controlled trial of continuous positive airway pressure and standard
      oxygen therapy in acute pulmonary oedema; effects on plasma brain natriuretic
      peptide concentrations.
AB  - AIMS: The study aim was to compare the effects of continuous positive airway
      pressure (CPAP) on clinical outcomes and plasma neurohormonal concentrations in
      patients with acute pulmonary oedema. METHODS AND RESULTS: In addition to
      standard therapy, 58 consecutive patients were randomized to receive 60% inhaled
      oxygen with or without CPAP at 7.5 cmH(2)O pressure. Clinical variables, symptoms
      and oxygenation were monitored and plasma epinephrine, norepinephrine and brain
      natriuretic peptide (BNP) concentrations estimated at 0, 1, 6 and 24 h. CPAP was
      associated with less breathlessness at 1 h (P<0.001), no treatment failures and
      more rapid resolution in respiratory rate (P<0.001), heart rate (P<0.001) and
      acidosis (P<0.005). Length of hospital stay was similar but there was a trend for
      a reduction in overall hospital mortality in the CPAP group (0.10>P>0.05). Plasma
      BNP concentrations rose progressively (P<0.001) before falling below admission
      concentrations at 24 h. Plasma neurohumoral concentrations were unaffected by
      CPAP treatment but were elevated in patients who died or had acute myocardial
      infarction. CONCLUSION: CPAP produces a more rapid clinical and symptomatic
      improvement in patients with acute pulmonary oedema, particularly within the
      first hour. CPAP is a useful adjunctive treatment in the early management of
      acute heart failure.

PMID- 12191750
TI  - A stepwise mapping approach for localization and ablation of ectopic right, left,
      and septal atrial foci using electroanatomic mapping.
AB  - AIMS: We describe a new strategic stepwise mapping approach for fast and accurate
      identification and ablation of ectopic atrial foci using an electroanatomic
      mapping system. METHODS AND RESULTS: Mapping procedures started with the
      acquisition of four points at the superior/septal part of the tricuspid annulus.
      According to this activation sequence, maps were continued towards the right
      atrial free wall if relatively early activation was shown at the superior part of
      the initial map or towards the triangle of Koch and, if necessary, to the left
      atrium, in cases of relatively early activation at the septum. High density
      mapping and detailed electrogram analysis only of the target area allowed
      identification and ablation of 34 foci in 30 of the 32 studied consecutive
      patients. A small number of mapping points were sufficient within a procedure
      time of 90 +/- 41 min for right 148 +/- 68 min and for left sided foci and a
      total fluoroscopy time of 9.6 +/- 7.2 min and 24.8 +/- 16.4 min respectively.
      Sixteen foci were located at the right free wall, eight at the left free wall,
      and 10 at the right or left side of the septum. CONCLUSION: Strategic
      electroanatomic mapping with fast identification of the area of tachycardia
      origin and high density mapping only of this target area allowed fast and
      successful localization and ablation of right and left free wall and septal
      ectopic atrial foci.

PMID- 12191751
TI  - Electrophysiologic investigation in Brugada syndrome; yield of programmed
      ventricular stimulation at two ventricular sites with up to three premature
      beats.
AB  - INTRODUCTION: Numerous reports on the inducibility of ventricular
      tachyarrhythmias (VT) in patients with atypical right bundle branch block and
      right precordial ST-elevation (Brugada syndrome) are based on multicentre studies
      that have used different stimulation protocols. Therefore, we prospectively
      investigated the inducibility of VT in these patients using a uniform protocol.
      METHODS: In 41 consecutive patients (29 males) showing a pattern of right bundle
      branch block and ST-elevation, programmed ventricular stimulation was performed
      in the right ventricular apex with up to three premature stimuli at sinus rhythm
      and at four different paced cycle lengths (500, 430, 370, and 330 ms) until
      refractoriness was reached or reproducible induction of a sustained (>30s) VT
      occurred. If a VT was not reproducibly inducible, the same protocol was repeated
      in the right ventricular outflow tract. RESULTS: A history of life-threatening
      events defined as syncope (n=17) or aborted sudden cardiac death (n=13) was
      present in 30 patients (73%); 11 individuals were asymptomatic. Inducibility
      (68%) was similar between symptomatic (n=21, 70%) and asymptomatic patients (n=7,
      64%). In 16 (39%) patients, VT were reproducibly inducible. If patients were only
      stimulated in the right ventricular apex, inducibility rate decreased to 39%. If
      only two premature beats at two sites were used it was as low as 32%. The mean
      coupling intervals of the second and third premature stimuli inducing sustained
      VT were short: 189+/-21 ms vs 186+/-22 ms, respectively. Forty-four percent of
      all patients (i.e. 64% of the inducible patients) had inducible VT only with
      coupling intervals shorter than 200 ms. CONCLUSIONS: The stimulation protocol
      markedly influences the extent of inducibility of VT in patients with right
      bundle branch block and ST-segment elevation. These findings question the
      significance of previous multicentre studies using different stimulation
      protocols and should have implications for further studies.

PMID- 12191752
TI  - Assay-based quantitative analysis of PC12 cell differentiation.
AB  - Differentiation of PC12 cells has been quantified by measurement of neurite
      length. However, this procedure is not suitable for large numbers of samples, for
      example in 96-well tissue culture plates. For this reason, we established three
      simple and quantitative methods for nerve growth factor-induced differentiation
      of PC12 cells cultured in 96-well plates. Firstly, because neuronal markers,
      including neurofilament proteins and beta-tubulin isotype III, are increased
      during PC12 cell differentiation, we developed cell enzyme-linked immunoabsorbent
      assays (ELISA)-based procedures that measure the amount of these proteins.
      Secondly, because lactate dehydrogenase (LDH) is down-regulated and mitochondrial
      NADH-dehydrogenase activity is increased during PC12 cell differentiation, we
      established procedures to measure changes in LDH and NADH dehydrogenase. We found
      that the cell ELISA and cell counting assays could be used to determine the
      degree of PC12 cell differentiation caused by nerve growth factor, basic
      fibroblast growth factor and epidermal growth factor. However, neither LDH nor
      NADH-dehydrogenase activities changed during Thy-1 antibody-induced
      differentiation. These findings show that in addition to the cell ELISA
      procedures, the LDH and NADH-dehydrogenase procedures are useful for
      characterization of growth factor-induced PC12 cell differentiation.

PMID- 12191753
TI  - Using machine vision to analyze and classify Caenorhabditis elegans behavioral
      phenotypes quantitatively.
AB  - Mutants with abnormal patterns of locomotion, also known as uncoordinated (Unc)
      mutants, have facilitated the genetic dissection of many important aspects of
      nervous system function and development in the nematode Caenorhabditis elegans.
      Although a large number of distinct classes of Unc mutants can be distinguished
      by an experienced observer, precise quantitative definitions of these classes
      have not been available. Here we describe a new approach for using automatically
      acquired image data to quantify the locomotion patterns of wild-type and mutant
      worms. We designed an automated tracking and imaging system capable of following
      an individual animal for long time periods and saving a time-coded series of
      digital images representing its motion and body posture over the course of the
      recording. We have also devised methods for measuring specific features from
      these image data that can be used by the classification and regression tree
      classification algorithm to reliably identify the behavioral patterns of specific
      mutant types. Ultimately, these tools should make it possible to evaluate with
      quantitative precision the behavioral phenotypes of novel mutants, gene knockout
      lines, or pharmacological treatments.

PMID- 12191754
TI  - Stimulus and recording variables and their effects on mammalian vestibular evoked
      potentials.
AB  - Linear vestibular evoked potentials (VsEPs) measure the collective neural
      activity of the gravity receptor organs in the inner ear that respond to linear
      acceleration transients. The present study examined the effects of electrode
      placement, analog filtering, stimulus polarity and stimulus rate on linear VsEP
      thresholds, latencies and amplitudes recorded from mice. Two electrode-recording
      montages were evaluated, rostral (forebrain) to 'mastoid' and caudal (cerebellum)
      to 'mastoid'. VsEP thresholds and peak latencies were identical between the two
      recording sites; however, peak amplitudes were larger for the caudal recording
      montage. VsEPs were also affected by filtering. Results suggest optimum high pass
      filter cutoff at 100-300 Hz, and low pass filter cutoff at 10,000 Hz. To evaluate
      stimulus rate, linear jerk pulses were presented at 9.2, 16, 25, 40 and 80 Hz. At
      80 Hz, mean latencies were longer (0.350-0.450 ms) and mean amplitudes reduced
      (0.8-1.8 microV) for all response peaks. In 50% of animals, late peaks (P3, N3)
      disappeared at 80 Hz. The results offer options for VsEP recording protocols.

PMID- 12191755
TI  - An implantable electrode design for both chronic in vivo nerve recording and axon
      stimulation in freely behaving crayfish.
AB  - A chronically implantable electrode design permitting alternate extracellular
      nerve recording and axon stimulation in freely behaving crayfish was developed.
      The electrode consists of a double hook made from 20 microm thin platinum wire
      that can be fitted to various nerve diameters, and is easily implantable. A fast
      curing, flexible two-component silicone was used for insulation. The double hook
      was connected to plugs and fixed on the carapace of a crayfish allowing the
      animals to roam freely. The setup also allows for repeated dis- and re-connection
      of the crayfish for alternating recording and stimulation. Two channel recordings
      were used to determine directionality and to discriminate between afferent
      activity of the two stretch receptor neurons and efferent activity of several
      motor neurons. In addition, they were also used to determine the conduction
      velocity of the recorded efferent activity. Stable two-channel recordings could
      be obtained for up to 5 months and 15 days without apparent effects on the
      animal. In vivo stimulation could be performed for at least 3 1/2 weeks. The
      implantable double hook is suitable for widespread use in invertebrate
      neurobiology.

PMID- 12191756
TI  - A novel technique for quantitative immunohistochemical imaging of various
      neurochemicals in a multiple-stained brain slice.
AB  - Here we describe a novel technique for comparative analysis of the distributions
      of various neurochemicals visualized using multiple immunohistochemistry in the
      same brain slice. As an example, the distributions of tyrosine hydroxylase,
      substance P and glutamate decarboxylase in coronal slices of rat brains were
      compared. Each slice was divided into approximately 220,000-300,000 microareas at
      20-microm intervals, and the immunohistochemical intensities of the three
      substances in each microarea were analyzed independently using a brain mapping
      analyzer; a microphotometry system previously developed in our laboratory (Sutoo
      et al., J. Neurosci. Methods, 1998; 85: 161-73). No significant differences
      between the distribution of each substance were observed in single- and triple
      labeled slices. We believe that this method will facilitate the investigation of
      the functions of the central nervous system and the disorders thereof in various
      diseases.

PMID- 12191757
TI  - A method to measure the effective spread of focally injected muscimol into the
      central nervous system with electrophysiology and light microscopy.
AB  - A method was developed to quantitate the volume of brain inactivated by muscimol
      focally injected. Tritiated muscimol was injected into the cerebellum and closely
      spaced sequential microelectrode recordings made at different depths by
      penetrations in an X-Y pattern centered at the injection site to evaluate changes
      in spontaneous activity in the tissue volume. Animals were euthanized after
      survivals from 40 min to 6 h, the cerebellum sectioned in the sagittal plane, and
      the sections dried onto glass slides. The slides were dipped in photographic
      emulsion, exposed in the dark and developed. Silver grain densities were
      quantitated by light microscopy from measured standards. The extent and
      concentration of bound, labeled muscimol co-varied with the observed reduction in
      recorded spontaneous activity. For future studies, the distribution and density
      of silver grains alone can serve as an accurate spatial indicator of the area of
      muscimol inactivation at high spatial resolution.

PMID- 12191758
TI  - Double round hybridization of membrane based cDNA arrays: improved background
      reduction and data replication.
AB  - Microarray analysis provides the ability to obtain gene expression data on
      thousands of gene targets in parallel and is being applied to an increasing
      variety of neurobiological samples. Nylon filter based cDNA arrays often provide
      an alternative to oligo-based or glass-based gene expression analysis systems.
      cDNA arrays regardless of the platform, are usually quite expensive to purchase
      and equally expensive to produce. As such, obtaining both high quality and
      replicated data, as well as the ability to recover from an apparently failed
      hybridization experiment are important factors in microarray experimental design.
      Using a collection of 1152 neuronally relevant cDNAs, this report describes
      simple modifications in experimental design of radioactive microarray experiments
      that, (1) improves reproducibility; (2) allows recovery from a failed experiment
      and; (3) provides a type of replicate data set with no requirement for additional
      arrays, no additional probe labelings, and little extra cost.

PMID- 12191759
TI  - Fluorescent zinc indicators for neurobiology.
AB  - Mounting evidence indicates that zinc has multiple roles in cell biology, viz. as
      a part of metalloenzyme catalytic sites, as a structural component of gene
      regulatory proteins, and (like calcium) as a free signal ion, particularly in the
      cortex of the brain. While most Zn(II) in the brain is tightly bound, such that
      free Zn(II) levels extracellularly and intracellularly are likely to be
      picomolar, a subset of glutamatergic neurons possess weakly bound zinc in
      presynaptic boutons which is released at micromolar levels in response to a
      variety of stimuli. Key to further progress in understanding the multiple roles
      of zinc will be the availability of fluorescent indicator systems that will
      permit quantitative determination and imaging of zinc fluxes and levels over a
      broad concentration range both intracellularly and extracellularly using
      fluorescence microscopy. Towards that end, we have compared a variety of
      fluorescent indicators for their sensitivity to Zn(II) and Cu(II), selectivity
      for Zn(II) in the presence of potential interferents such as Ca(II) or Mg(II),
      and potential for quantitative imaging. The commercially available probes Fura-2,
      Mag-Fura-5, Newport Green DCF, and FuraZin-1 were compared with the carbonic
      anhydrase-based indicator systems for selectivity and sensitivity. In addition,
      intracellular levels of Zn following excitotoxic insult were determined by single
      pixel fluorescence lifetime microscopy of Newport Green DCF, and extracellular
      levels of free zinc following stimulus of rat hippocampal slices were determined
      ratiometrically with a carbonic anhydrase-based indicator system. These results
      suggest that zinc ion at high nM to microM levels can be accurately quantitated
      by FuraZin-1 ratiometrically or by Newport Green DCF by fluorescence lifetime;
      and at levels down to pM by intensity ratio, lifetime, or polarization using
      carbonic anhydrase-based systems.

PMID- 12191760
TI  - A low-noise flexible integrated system for recording and analysis of multiple
      electrical signals during sleep-wake states in rats.
AB  - A low-noise flexible system for the simultaneous recording and analysis of
      several electrical signals (EEG, ECG, EMG, and diaphragm EMG) from the same rat
      was constructed for studying changes in physiological functions during the sleep
      wake cycle. The hardware in the system includes a multichannel amplifier, a video
      camera, a timer code generator, and a PC. A miniature buffer headstage with high
      input impedance connected to a 6-channel amplifier was developed. All electrical
      activities devoid of 60 Hz interference could be consistently recorded by our low
      cost amplifier with no shielding treatment. The analytical software was
      established in the LabVIEW environment and consisted of three major frames:
      temporal, spectral, and nonlinear analyses. These analytical tools demonstrated
      several distinct utilities. For example, the sleep-wake states could be
      successfully distinguished by combining temporal and spectral analyses. An
      obvious theta rhythm during rapid-eye-movement sleep (REMS) was recorded from
      parietal to occipital cortical areas but not from the frontal area. In addition,
      two types of sleep apnea with/without cardiac arrhythmias were observed under
      REMS condition. Moreover, the evoked potentials of the primary somatosensory
      cortex elicited by innocuous electrical pulses were modulated by vigilant states,
      especially under a slow-wave sleep state. These results show that our system
      delivers high-quality signals and is suitable for sleep investigations. The
      system can be easily expanded by combining other recording devices, like a
      plethysmograph. This compact system can also be easily modified and applied to
      other related physiological or pharmacological studies.

PMID- 12191761
TI  - EEG measurements by means of radiotelemetry after intracerebroventricular (ICV)
      cannulation in rodents.
AB  - The utility of implanted radiotelemetry transmitters for the measurement of
      electroencephalogram (EEG), locomotor activity, body temperature and
      cardiovascular parameters has been well documented. This paper focuses on the
      methodology, of combining radiotelemetry with intracerebroventricular (ICV)
      cannulation. The two excitatory neuropeptides, orexin-A and orexin-B, can only be
      given by ICV injection, therefore we examined their effects on the normal sleep
      wake cycle of rodents in the present study. The effects of orexins on sleep
      architecture have been extensively studied in tethered models demonstrating
      increased levels of wakefulness. In this study, both orexin neuropeptides,
      especially orexin-A, increase wakefulness within the first sleep period followed
      by an increase in slow wave (SW) sleep and paradoxical sleep (PS), towards the
      end of a 5-h recording period which may be a rebound phenomena. The present study
      has demonstrated that ICV cannulation can be used effectively in studying the
      effects of pharmacological agents on the sleep-wake cycle of rodents by measuring
      EEG and EMG by radiotelemetry.

PMID- 12191763
TI  - Functions of outer membrane receptors in mitochondrial protein import.
AB  - Most mitochondrial proteins are synthesized in the cytosol as precursor proteins
      and are imported into mitochondria. The targeting signals for mitochondria are
      encoded in the presequences or in the mature parts of the precursor proteins, and
      are decoded by the receptor sites in the translocator complex in the
      mitochondrial outer membrane. The recently determined NMR structure of the
      general import receptor Tom20 in a complex with a presequence peptide reveals
      that, although the amphiphilicity and positive charges of the presequence is
      essential for the import ability of the presequence, Tom20 recognizes only the
      amphiphilicity, but not the positive charges. This leads to a new model that
      different features associated with the mitochondrial targeting sequence of the
      precursor protein can be recognized by the mitochondrial protein import system in
      different steps during the import.

PMID- 12191764
TI  - The mitochondrial import machinery: preprotein-conducting channels with binding
      sites for presequences.
AB  - Mitochondrial preproteins with amino-terminal presequences must cross two
      membranes to reach the matrix of the organelle. Both outer and inner membranes
      contain hydrophilic high-conductance channels that are responsible for selective
      translocation of preproteins. The channels are embedded in dynamic protein
      complexes, the TOM complex of the outer membrane and the TIM23 complex of the
      inner membrane. Both channel-forming proteins, Tom40 and Tim23, carry specific
      binding sites for presequences, but differ in their pore size and response to a
      membrane potential. Studies with the TOM machinery show that other subunits of
      the translocase complex also provide specific binding sites for preproteins,
      modulate the channel activity and are critical for assembly of the channel.

PMID- 12191765
TI  - Protein import into and across the mitochondrial inner membrane: role of the
      TIM23 and TIM22 translocons.
AB  - Import of nuclear-encoded mitochondrial proteins requires the action of at least
      two different import machines, called translocons, in the mitochondrial inner
      membrane (IM). The TIM23 complex mediates the translocation of proteins into the
      mitochondria matrix, whereas the TIM22 complex is required for the insertion of
      polytopic proteins into the IM. While the two translocons are distinct and
      composed of separate subunits, the essential reactions in each complex are
      carried out by homologous proteins. In addition, the core components of both the
      TIM23 and TIM22 translocons have been shown to form aqueous pores in the
      mitochondrial IM. In this review, we summarize what is known about import of
      proteins across the mitochondrial IM.

PMID- 12191766
TI  - Delivery of nascent polypeptides to the mitochondrial surface.
AB  - Thousands of polypeptides with diverse biochemical properties, some of which are
      extremely hydrophobic, are targeted from cytoplasmic ribosomes to the surface of
      mitochondria. Localised synthesis, as well as transient interactions with a wide
      array of molecular chaperones and other cytoplasmic factors, can promote
      productive interaction of mitochondrial proteins with the TOM complex to initiate
      protein import into mitochondria.

PMID- 12191767
TI  - Contact sites between the outer and inner membrane of mitochondria-role in
      protein transport.
AB  - Many essential functions of mitochondrial metabolism have been studied in the
      past three decades in considerable depth: oxidative phosphorylation, catabolism
      of fatty acids, role in nitrogen metabolism, and amino acid metabolism. More
      recently, other aspects attracted much attention like protein translocation into
      mitochondria, inheritance of mitochondrial DNA, movement of mitochondria, their
      fusion and fission, and their involvement in apoptosis, ageing, cancer and other
      cellular processes. Together with these new views on the function of
      mitochondria, new ideas on the structure of mitochondria emerged. Here we will
      discuss the current knowledge about how the membranes of mitochondria are
      organized and how they interact. Interactions between components of the inner and
      the outer membrane are necessary for a number of central mitochondrial functions
      such as the channeling of metabolites, coordinated fusion and fission of
      mitochondria, and protein transport. Some of these interactions appear stable
      such as the so-called morphological contact sites; others are quite dynamic.
      Direct evidence that a certain protein is part of morphologically defined contact
      sites is lacking. Nevertheless, protein translocase complexes of the outer and
      the inner membrane exhibit stable interactions between the two membranes when
      precursor proteins are arrested during import into mitochondria. Finally, we
      discuss possible roles of cristae junctions, another morphologically defined
      membrane structure in mitochondria.

PMID- 12191768
TI  - Molecular chaperones as essential mediators of mitochondrial biogenesis.
AB  - Chaperone proteins have been initially identified by their ability to confer
      cellular resistance to various stress conditions. However, molecular chaperones
      participate also in many constitutive cellular processes. Mitochondria contain
      several members of the major chaperone families that have important functions in
      maintaining mitochondrial function. The major Hsp70 of the mitochondrial matrix
      (mtHsp70) is essential for the translocation of cytosolic precursor proteins
      across the two mitochondrial membranes. MtHsp70 interacts with the preprotein in
      transit in an ATP-dependent reaction as it emerges from the translocation channel
      of the inner membrane. Together with two essential partner proteins, Tim44 and
      Mge1, mtHsp70 forms a membrane-associated import motor complex responsible for
      vectorial polypeptide movement and unfolding of preprotein domains. Folding of
      newly imported proteins in the matrix is assisted by the soluble chaperone system
      formed by mtHsp70 and its partner protein Mdj1. For certain substrate proteins,
      the protected folding environment that is offered by the large oligomeric Hsp60
      complex facilitates further folding reactions. The mitochondrial Hsp70 Ssq1 is
      involved in the assembly of mitochondrial Fe/S clusters together with another
      member of the DnaJ family, Jac1. Chaperones of the Clp/Hsp100 family mediate the
      prevention of aggregation under stress conditions and eventually the degradation
      of mitochondrial proteins. Together, the chaperones of the mitochondrial matrix
      form a complex interdependent chaperone network that is essential for most
      reactions of mitochondrial protein biogenesis.

PMID- 12191769
TI  - Mitochondrial processing peptidases.
AB  - Three peptidases are responsible for the proteolytic processing of both nuclearly
      and mitochondrially encoded precursor polypeptides targeted to the various
      subcompartments of the mitochondria. Mitochondrial processing peptidase (MPP)
      cleaves the vast majority of mitochondrial proteins, while inner membrane
      peptidase (IMP) and mitochondrial intermediate peptidase (MIP) process specific
      subsets of precursor polypeptides. All three enzymes are structurally and
      functionally conserved across species, and their human homologues begin to be
      recognized as potential players in mitochondrial disease.

PMID- 12191770
TI  - Insertion of proteins into the inner membrane of mitochondria: the role of the
      Oxa1 complex.
AB  - The inner mitochondrial membrane harbors a large number of proteins that display
      a wide range of topological arrangements. The majority of these proteins are
      encoded in the cell's nucleus, but a few polytopic proteins, all subunits of
      respiratory chain complexes are encoded by the mitochondrial genome. A number of
      distinct sorting mechanisms exist to direct these proteins into the mitochondrial
      inner membrane. One of these pathways involves the export of proteins from the
      matrix into the inner membrane and is used by both proteins synthesized within
      the mitochondria, as well as by a subset of nuclear encoded proteins. Prior to
      embarking on the export pathway, nuclear encoded proteins using this sorting
      route are initially imported into the mitochondrial matrix from the cytosol,
      their site of synthesis. Protein export from the matrix into the inner membrane
      bears similarities to Sec-independent protein export in bacteria and requires the
      function of the Oxa1 protein. Oxa1 is a component of a general protein insertion
      site in yeast mitochondrial inner membrane used by both nuclear and mitochondrial
      DNA encoded proteins. Oxa1 is a member of the conserved Oxa1/YidC/Alb3 protein
      family found throughout prokaryotes throughout eukaryotes (where it is found in
      mitochondria and chloroplasts). The evidence to demonstrate that the
      Oxa1/YidC/Alb3 protein family represents a novel evolutionarily conserved
      membrane insertion machinery is reviewed here.

PMID- 12191771
TI  - Membrane protein degradation by AAA proteases in mitochondria.
AB  - The inner membrane of mitochondria is one of the protein's richest cellular
      membranes. The biogenesis of the respiratory chain and ATP-synthase complexes
      present in this membrane is an intricate process requiring the coordinated
      function of various membrane-bound proteins including protein translocases and
      assembly factors. It is therefore not surprising that a distinct quality control
      system is present in this membrane that selectively removes nonassembled
      polypeptides and prevents their possibly deleterious accumulation in the
      membrane. The key components of this system are two AAA proteases, membrane
      embedded ATP-dependent proteolytic complexes, which expose their catalytic sites
      at opposite membrane surfaces. Other components include the prohibitin complex
      with apparently chaperone-like properties and a regulatory function during
      proteolysis and a recently identified ATP-binding cassette (ABC) transporter that
      exports peptides derived from the degradation of membrane proteins from the
      matrix to the intermembrane space. All of these components are highly conserved
      during evolution and appear to be ubiquitously present in mitochondria of
      eukaryotic cells, indicating important cellular functions. This review will
      summarize our current understanding of this proteolytic system and, in
      particular, focus on the mechanisms guiding the degradation of membrane proteins
      by AAA proteases.

PMID- 12191773
TI  - Oropharyngeal candidiasis in HIV(+) patients may influence the selection of HIV-1
      protease variants.
AB  - Approximately 500 HIV-1 protease gene (pro) sequences were obtained from oral
      tissues (gingival cuff, buccal mucosa, tongue, palate) as well as saliva and
      peripheral blood mononuclear cells (PBMC) of 80 HIV-1 positive patients by nested
      amplification and manual sequencing of PCR products. By visual inspection each
      patient in this study exhibited a unique sequence profile. HIV-1 pro sequences
      obtained from patients with oropharyngeal candidiasis (OPC(+) patients) had
      significantly higher numbers of mutations than sequences from OPC(-) patients,
      but OPC(+) patients were no more likely to accumulate protease inhibitor
      resistance mutations than OPC(-) patients. Although the sequences for each
      patient were predominantly consistent between PBMC and oral tissues,
      approximately 10% of the patients demonstrated tissue specificity, and patients
      that demonstrated tissue specificity tended to be OPC(+). Furthermore, HIV-1 pro
      sequences derived from OPC lesions demonstrated unique mutations in approximately
      30% of the patients who provided paired OPC(+/-) samples of the same tissue type.
      These data provide evidence for minimal compartmentalization of HIV-1 in oral
      tissues, yet some patients demonstrate minor variation between the HIV-1 pro
      sequences obtained from an OPC lesion and those obtained from a non-lesion site
      of similar tissue.

PMID- 12191772
TI  - Import and assembly of proteins into mitochondria of mammalian cells.
AB  - Most of our knowledge regarding the process of protein import into mitochondria
      has come from research employing fungal systems. This review outlines recent
      advances in our understanding of this process in mammalian cells. In particular,
      we focus on the characterisation of cytosolic molecular chaperones that are
      involved in binding to mitochondrial-targeted preproteins, as well as the
      identification of both conserved and novel subunits of the import machineries of
      the outer and inner mitochondrial membranes. We also discuss diseases associated
      with defects in import and assembly of mitochondrial proteins and what is
      currently known about the regulation of import in mammals.

PMID- 12191774
TI  - Sequence and phylogenetic analysis of the L and VP1 genes of foot-and-mouth
      disease virus serotype Asia1.
AB  - Most of the molecular epidemiological studies of foot-and-mouth disease virus
      (FMDV) are based on comparison of VP1 gene sequence. In this report, we determine
      the nucleotide (nt) sequence of the L (603 nt) and VP1 (633 nt) genes of 27 FMDV
      serotype Asia 1 isolates recovered from different outbreaks in India, and
      compared with each other and the vaccine strain, IND 63/72, used in the country.
      Independent phylogenetic analyses on both the aligned gene sequences identified
      two major lineages (designated A & B) in the Asia 1 isolates. Both L- and VP1
      based trees were congruent with respect to the major branching pattern of the
      isolates. The lineage A is represented by the isolates of 1986-2000 including the
      vaccine strain IND 63/72, whereas, lineage B appeared to be dominant and
      responsible for most of the recent outbreaks. A correlation was observed between
      the clustering of the isolates in the phylogenetic tree and the amino acid
      changes at many of the positions in VP1 as well as in L protein. The annual rate
      of evolution in L and VP1 genes was found similar and estimated to be 4.0 x 10(
      3) and 3.8 x 10(-3) substitutions per nucleotide, respectively. Our result,
      largely from the congruence in phylogenetic trees and the rate of evolution in
      both the genes, suggests the possibility for the use of L gene sequence in
      phylogenetic comparison of FMDV.

PMID- 12191775
TI  - Nonsense mutations of replicase and movement protein genes contribute to the
      attenuation of an avirulent tomato mosaic virus.
AB  - Three recovery mutants of an avirulent Tomato mosaic virus genus: (Tobamovirus)
      (ToMV-K) with back mutations of the replicase and/or movement protein (MP) genes,
      have been constructed by site-directed mutagenesis, and infectious plasmids
      (pToMV-K) were obtained. The rescued phenotypes of the progeny viruses showed
      that the replicase and MP recovery mutant (ToMV-K(rase-mp)) induced severe
      symptoms on both systemic and necrotic plants similar to those induced by the
      virulent strain. The replicase back mutant (ToMV-K(rase)) produced chlorosis and
      mosaic symptoms on N. tabacum cv. Huangmiaoyu (systemic host), while the MP
      recovery mutant (ToMV-K(mp)) produced no systemic symptoms on Huangmiaoyu
      tobacco. Sequencing of the cDNA of progeny viruses revealed that the "back
      mutants" maintained these mutation sites during infection. Protein immunoblots
      indicated that the 98 and 126 kDa proteins were expressed in the plants
      systemically infected by ToMV-K and pToMV-K, whereas no 98 kDa protein was
      detected in the plants infected by ToMV. The MPs (27 kDa) of ToMV-K and pToMV-K
      in the plants were smaller in size than those (30 kDa) of ToMV and pToMVK(rase
      mp). These data suggest that ToMV-K replicates and spreads by expressing the
      truncated 98 and 126 kDa replicases and 27 kDa MP in plants. The opal mutation at
      nucleotides (nt) 2670-2672 of the replicase gene mainly contributes to the
      attenuation of ToMV-K, whereas the mutations at nt 5632-5664 of the MP gene
      attenuate the induced symptoms.

PMID- 12191776
TI  - Expression of the human CD4 receptor is sufficient for the transduction of murine
      T-cells with MLV/HIV pseudotyped vectors.
AB  - Murine leukemia virus (MLV) can be pseudotyped with a variant of the HIV envelope
      gene encoding the surface glycoprotein gp120-SU and a carboxyl-terminally
      truncated transmembrane (TM) protein, with only seven cytoplasmic amino acids.
      MLV/HIV pseudotyped retroviral vectors selectively target human CD4+ cells and
      can be used as tools to study entry of HIV into cells. Mouse T-cells are immune
      to HIV infection, which is primarily caused by the weak binding affinity of HIV
      gp120 to the murine CD4 receptor. Here we show that expression of the human CD4
      receptor in murine T-cells is sufficient for syncytia formation with HIV-1
      envelope expressing cells and entry of MLV/HIV pseudotyped retroviral vectors.
      This implies that the murine CXCR4 receptor is a functional coreceptor for
      MLV/HIV pseudotyped vectors and confirms previous data that the inability of HIV
      to replicate in murine T-cells is due to a post entry block.

PMID- 12191777
TI  - Identification of human hepatocyte protein(s), which binds specifically to the
      recombinant envelope-2/non-structural-1 protein of hepatitis C virus.
AB  - Hepatitis C virus (HCV), which is the major pathogen responsible for human
      chronic liver disease, has special tropism for hepatocytes. Although, low-density
      lipoprotein receptor, CD81 and negatively charged glycosaminoglycans have been
      proposed as candidate receptors for HCV, no confirmed receptor(s) on the
      hepatocytes have been identified to date. It is also suggested that additional,
      yet unidentified, cellular proteins may be involved in the host-viral
      interaction. Therefore, this study was conducted with the main aim to identify
      hepatocyte protein(s) that may have affinity for the HCV structural protein,
      envelope-2/non-structural-1 (E2/NS1) protein. For the binding studies,
      hepatocytes were isolated from fresh normal human liver tissues. The hepatocyte
      proteins on the nitrocellulose paper were reacted with recombinant E2/NS1 protein
      and anti-E2 (rabbit). In another approach, to rule out the possibility of binding
      of rec-E2/NS1 with the hepatocyte cytoplasmic proteins, hepatocyte plasma
      membrane proteins were passed through CNBr-activated and recombinant E2/NS1 bound
      sepharose-4B column. The recombinant E2/NS1 binding hepatocyte plasma membrane
      protein(s) were eluted and were then analyzed. Altogether, our data suggest that
      E2/NS1 protein of HCV binds to two hepatocyte proteins of molecular weights 25-28
      kDa and 59-60 kDa. These results indicate the possible role of the above proteins
      (25-28 kDa and 59-60 kDa) in the viral binding to the hepatocytes.

PMID- 12191778
TI  - Expression of PrP(C) as HIS-fusion form in a baculovirus system and conversion of
      expressed PrP-sen to PrP-res in a cell-free system.
AB  - Conversion of the PrP cellular form (PrP(C)) to the pathogenic form (PrP(Sc)) is
      the key step in the pathogenesis of transmissible spongiform encephalophathies.
      Although the mechanism of conformational conversion of PrP proteins remains
      uncertain, the cell-free conversion reaction and other in vitro PrP amplification
      tests allow it to be studied under the much quicker and simpler conditions than
      those of transmission bioassay in vivo. Using baculovirus expression system, wild
      type hamster (HaPrP) and human PrP (HuPrP), as well as D178N mutated human PrP
      (HuPrPm178) were expressed in HIS-fusion form. After 35S-methionine labeling and
      purification with Ni-NTA agarose affinity chromatography, individual expressed
      PrP proteins were mixed with PrP(Sc) isolated from hamster brain tissue infected
      with scrapie 263K. Protease-resistant isoform was detected in the homologous
      HaPrP reaction, but not in the two heterologous HuPrP preparations, implying a
      species-specific molecular recognition between PrP(C) and PrP(Sc). HIS-tag in HIS
      HaPrP seems to have little effect on the formation of protease-resistant protein
      in this preparation. This system proposes a simple and protein productive
      enriched way for cell-free conversion of prion proteins, as the replacement of
      native or genetic engineering expressed sole PrP(C) from mammalian or non
      mammalian sources.

PMID- 12191779
TI  - Molecular characterization of an isolate from the 1989/90 epizootic of Ebola
      virus Reston among macaques imported into the United States.
AB  - We have determined the entire genomic sequence of the Pennsylvania strain, which
      was isolated along with the Virginia strain during the emergence of Ebola virus
      Reston in 1989/90 in the United States. Thus, either the Pennsylvania or Virginia
      strain, neither of which had been previously molecularly characterized, can be
      considered as the prototype for Ebola virus Reston. Comparative analysis showed a
      high degree of homology to the concomitantly analyzed and recently published
      Philippine strain of EBOV Reston from 1996 (Ikegami et al., Arch. Virol., 146
      (2001) 2021). In comparison to EBOV Zaire, strain Mayinga, conservation could be
      found within the open reading frames, the 3' leader and 5' trailer region and the
      transcriptional signals, whereas the non-coding and intergenic regions did not
      show any homology. This clearly supports that EBOV Reston is a distinct species
      within the genus Ebola-like virus but which seems to be similar to other members
      with respect to transcription and replication strategies. The sequence
      determination provides the basis for the development of a reverse genetics system
      for Ebola virus Reston, which is needed to study differences in pathogenicity
      among filoviruses.

PMID- 12191780
TI  - Viruses detected in the caecum contents of healthy pigs representing a new
      genetic cluster in genogroup II of the genus "Norwalk-like viruses".
AB  - Viruses of the genus 'Norwalk-like viruses' (NLVs) detected in humans have been
      genetically classified into two major genetic groups, genogroups I and II (GI and
      GII), which together are made up of at least 14 genetic subgroups. However, a
      comparable classification of NLVs in other species remains to be carried out. We
      sequenced a 2-kb region from within the RNA polymerase gene to the 3' end of open
      reading frame 2 (ORF2) of two NLV strains previously detected in the caecum
      contents of healthy pigs. The sequences of the entire ORF2 of these two NLV
      strains were analyzed for their genetic relationships to 15 human strains, which
      have already been reported and used as references for the genetic classification
      of human NLV strains, and additional two strains; one, a human strain which has
      recently been reported and appears to represent a new genetic subgroup of GII;
      and the other, an animal NLV strain. Analysis of a matrix showing pairwise
      identities and topology of a neighbor-joining tree showed that the two swine
      strains could be classified into a new genetic subgroup of GII on the basis of
      the amino acid sequences of the entire capsid protein. Grouping of the two swine
      strains was well corroborated by results of similar analyses of nucleotide
      sequences of the entire ORF2 and of a 510 base region at the 3' end of ORF1.

PMID- 12191781
TI  - Phylogenetic analysis of H1N2 isolates of influenza A virus from pigs in the
      United States.
AB  - Twenty-four H1N2 influenza A viruses were newly isolated from pigs in the United
      States. These isolates originated from 19 farms in 9 different swine producing
      states between 1999 and 2001. All farms had clinical histories of respiratory
      problem and/or abortion. The viral isolates were characterized genetically to
      determine the origin of all eight gene segments. The results showed that all H1N2
      isolates were reassortants of classical swine H1N1 and triple reassortant H3N2
      viruses. The neuraminidase (NA) and PB1 genes of the H1N2 isolates were of human
      origin, while the hemagglutinin (HA), nucleoprotein (NP), matrix (M), non
      structural (NS), PA and PB2 polymerase genes were of avian or swine origin.
      Fifteen of the 24 H1N2 isolates were shown to have a close phylogenic
      relationship and high amino acid homology with the first US isolate of H1N2
      (A/SW/IN/9K035/99). The remaining nine isolates had a close phylogenic
      relationship with classical swine influenza H1N1 in the HA gene. All other genes
      including NA, M, NP, NS, PA, PB1 and PB2 showed a close phylogenic relationship
      with the H1N2 (A/SW/IN/9K035/99) strain and triple reassortant H3N2 viruses.
      However, PB1 genes of two isolates (A/SW/KS/13481-S/00, A/SW/KS/13481-T/00) were
      originated from avian influenza A virus lineage. These results suggest that
      although there are some variations in the HA genes, the H1N2 viruses prevalent in
      the US swine population are of a similar genetic lineage.

PMID- 12191786
TI  - Prior experience with bromocriptine in the home cage attenuates locomotor
      sensitization in rats.
AB  - The dopamine D(2) agonist bromocriptine has a long lasting, biphasic effect on
      locomotion, causing decreased activity during the first 60-90 min after the
      injection, followed by increased activity that peaks 90-180 min after the
      injection. In Experiment 1, repeated injections of 5.0 mg/kg bromocriptine
      produced rapid development of locomotor sensitization when rats were placed in
      activity chambers for 90 min immediately following each injection. Once
      sensitization had occurred, expression of sensitization was enhanced when the
      rats were tested for 90 min beginning 90 min after the injection. In contrast,
      when rats were placed in the activity chambers for 90 min after spending the
      first 90 min following each injection of bromocriptine in their home cage, the
      onset of locomotor sensitization was delayed and expression of sensitization was
      reduced. In Experiment 2, this inhibition of sensitization did not occur when
      rats spent the first 90 min following each injection of bromocriptine in a cage
      that was identical to their home cage, but was not their home cage. Thus,
      spending the first 90 min after the injection of bromocriptine in the home cage
      somehow inhibits the development of locomotor sensitization during the subsequent
      90 min of each session. These data are consistent with other data indicating that
      repeated injections of drugs in the home cage often fail to produce the locomotor
      sensitization that is observed when these injections occur in novel cages.

PMID- 12191787
TI  - The meninges contribute to the conditioned taste avoidance induced by neural
      cooling in male rats.
AB  - After consumption of a novel sucrose solution, temporary cooling of neural areas
      that mediate conditioned taste avoidance can itself induce conditioned avoidance
      to the sucrose. It has been suggested that this effect is either a result of
      inactivation of neurons in these areas or of cooling the meninges. In a series of
      studies, we demonstrated that cooling the outer layer of the meninges, the dura
      mater, does not contribute to the conditioned taste avoidance induced by cooling
      any of these areas. The present experiments were designed to determine whether
      the inner layers of the meninges are involved. If they are involved, then one
      would expect that cooling locations in the brain that do not mediate conditioned
      taste avoidance, such as the caudate putamen (CP), would induce conditioned taste
      avoidance as long as the meninges were cooled as well. One also would expect that
      cooling neural tissue without cooling the meninges would reduce the strength of
      the conditioned taste avoidance. Experiment 1 established that the temperature of
      the neural tissue and meninges around the cold probes implanted in the CP were
      cooled to temperatures that have been shown to block synaptic transmission.
      Experiment 2 demonstrated that cooling the caudate putamen and overlying cortex
      and meninges induced conditioned taste avoidance. In experiment 3, a circle of
      meninges was cut away so that the caudate putamen and overlying cortex could be
      cooled without cooling the meninges. The strength of the conditioned taste
      avoidance was substantially reduced, but it was not entirely eliminated. These
      data support the hypothesis that cooling the meninges contributes to the
      conditioned taste avoidance induced by neural cooling. They also allow the
      possibility that neural inactivation produces physiological changes that can
      induce conditioned taste avoidance.

PMID- 12191788
TI  - Restricted daily access to water and voluntary nicotine oral consumption in mice:
      methodological issues and individual differences.
AB  - Nicotine (NIC) shares most of the characteristics of other addictive drugs.
      However, attempts to establish oral self-administration failed under an ad
      libitum fluid availability. Outbred mice were scheduled to a restricted 2 h/day
      water access. In Experiment I, such schedule elevated corticosterone blood
      levels, which were strongly reduced following the drinking session. In two
      replications of Experiment II, mice had several days of free choice between water
      or NIC (10 mg/l). A consistent and reliable preference for NIC was found. Mice
      also progressively increased their drug intake in a fading study. In Experiment
      III, levels of cotinine (the principal NIC biomarker in the blood) confirmed
      pharmacologically active drug concentrations after oral intake. In Experiment IV,
      another set of mice was exposed to a 6-days 'passive' nicotine consumption, by
      masking the drug taste with 10% sucrose. After sucrose removal, a preference for
      NIC emerged, which however vanished during the following days. This 'neutral'
      profile resulted to be the combined performance of a NIC-preferring and a NIC-non
      preferring subpopulations. In conclusion, a clear-cut preference for NIC can be
      easily established when the drug offer is concurrent to a restricted access to
      water. The present paradigm may be useful to investigate issues of NIC
      dependence.

PMID- 12191789
TI  - Brain system size and adult-adult play in primates: a comparative analysis of the
      roles of the non-visual neocortex and the amygdala.
AB  - Recent studies have shown that contrary to expectation, larger-brained species
      within mammalian orders are not more likely to engage in play. This is true for
      juvenile rodents, juvenile marsupials and adult primates. Neither does the
      relative size of the neocortex predict the prevalence of play in species of
      marsupials and primates. Two methodological limitations may account for the lack
      of such relationships. Firstly, play may only vary systematically with specific
      brain areas, not overall size increases in brain tissue. Secondly, the play
      indices used to measure the variation in play across species may be
      insufficiently sensitive to the effects of changes in brain size. In this study,
      we attempt to deal with the first methodological problem. The adult-adult play
      fighting among species of primates was correlated with the relative size of the
      non-visual cortex and the amygdala. The statistical analyses used took into
      account the problems of scaling and corrected for degree of phylogenetic
      relatedness among the species. The size of the non-visual cortex failed to
      predict the prevalence of play fighting occurring in either sexual or non-sexual
      contexts. In contrast, the size of the amygdala significantly predicted the
      prevalence of sexual play, but not non-sexual play. That is, species with larger
      sized amygdala are more likely to engage in sexual play. These findings provide
      new insights into the role of different brain systems in the regulation of play
      behavior.

PMID- 12191790
TI  - Relation of behaviour and macrophage function to life span in a murine model of
      premature immunosenescence.
AB  - According to our previous work, mice of the same strain and age show striking
      inter-individual differences in behaviour when exposed to a T-maze test. Further,
      the animals exploring the maze slowly (slow mice) or staying at the starting
      point (freezing behaviour), which show high levels of emotionality/anxiety in
      other standard behavioural tests, have a less competent immune system (earlier
      immunosenescence) than those which explore it quickly (fast mice). The present
      longitudinal study on OF-1 Swiss female mice confirms and extends the above
      findings. Thus, the animals showing a lower performance in the T-test (slow mice)
      which is accompanied by a poor neuromuscular coordination in a tightrope test,
      have a shorter life span than the good performers (fast mice). Moreover, the slow
      mice have a less competent immune system as regards the following functions of
      peritoneal macrophages: adherence to substrate, chemotaxis, ingestion of
      particles and superoxide anion production. This suggests that, at the same
      chronological age and as regards their immune competence, the slow mice are
      biologically older than the fast mice. This agrees with current ideas on the
      close functional relationship between the nervous and the immune system in the
      physiological adaptation to stress, and supports the concept that an optimum
      level of performance of these two systems is needed to attain a long life span.

PMID- 12191791
TI  - Evaluation of the elevated plus-maze and open-field tests for the assessment of
      anxiety-related behaviour in inbred mice.
AB  - The elevated plus-maze test (PM) and open-field test (OF) are routinely used to
      study anxiety-related behaviour in mouse. However, the data obtained with these
      tests have often been contradictory, probably because of differences between
      laboratories in the selection and analysis of behavioural parameters. We have
      characterised the pattern of mouse anxiety by analysing a number of behavioural
      parameters with both PM and OF in BALB/c and C57BL/6 mice, two behaviourally
      distant mouse strains. Twenty-eight variables (15 analysed with PM and 13 with
      OF) were selected by correlation analysis from those initially recorded with both
      tests. The scores of the selected variables were first analysed by MANOVAs, and
      then by principal component analysis (PCA). PCA extracted five factors for PM and
      four factors for OF. These factors were subjected to a correlation analysis,
      which showed significant correlation between four of them. The factorial scores
      of BALB/c and C57BL/6 mice were analysed by MANOVAs, which showed significant
      effects of both the strain and test used. Our results confirm the
      multidimensional structure of mouse anxiety-related behaviour as regards both
      simple components and functional interactions, and comprehensively represent
      strain- and test-specific features of mouse anxiety-related behaviour.

PMID- 12191792
TI  - Global motion detection is impaired in cats deprived early of pattern vision.
AB  - We investigated global motion detection in binocularly deprived cats (BD cats)
      and control cats (C cats). The cats were trained in the two-choice free running
      apparatus for a food reward. The positive stimulus was a moving random-dot
      pattern with all dots moving in one direction, the negative stimulus was the same
      random-dot pattern but stationary. The BD cats were severely impaired in
      detection of global motion stimulus as compared with the C cats. In contrast,
      their level of performance in a simple relative motion detection task (one
      square) did not differ from that in the C cats. However, in more complex relative
      motion detection task (two squares) the performance of the BD cats was impaired.
      The deficit in the detection of global motion in BD cats may be due to
      impairments of their Y-pathway.

PMID- 12191793
TI  - Septal vasopressin induced preservation of social recognition in rats was
      abolished by pinealectomy.
AB  - The role of intraseptal vasopressin (AVP) and the pineal gland in the modulation
      of social memory was investigated. For social recognition, male pinealectomised
      (Px) and sham-operated (SO) rats were confronted with juveniles for 4 min, and
      injected with either 200 pg AVP or 5 ng of its V1 receptor antagonist
      d(CH2)5Tyr(Me)AVP (AAVP) into the mediolateral septum. Re-exposure to the same
      and a different juvenile took place after 30 or 120 min. In SO rats, the social
      memory was facilitated after injection of AVP (120 min) and impaired after AAVP
      application (30 min). In Px rats, however, neither AVP nor AAVP administration
      influenced the social memory. Comparison between SO and Px control groups treated
      with artificial cerebrospinal fluid did not reveal any differences as to social
      recognition responses. After subcutaneous administration of 250 microg melatonin
      (substitution for pinealectomy) the social discrimination responses in Px rats
      after peptide application were influenced in a manner identical to that noted in
      SO animals. These findings suggest that the modulation of social memory by
      intraseptal AVP is dependent on an intact pineal function.

PMID- 12191794
TI  - Yawning/cortical activation induced by microinjection of histamine into the
      paraventricular nucleus of the rat.
AB  - The effects of microinjection of histamine into the paraventricular nucleus (PVN)
      of the hypothalamus on yawning responses were investigated in anesthetized,
      spontaneously breathing rats. Yawning responses were evaluated by monitoring the
      intercostal electromyogram (EMG) as an index of inspiratory activity and
      digastric EMG as an indicator of mouth opening. We also recorded the
      electrocorticogram (ECoG) to determine the arousal response during yawning.
      Autonomic function was evaluated by measuring blood pressure and heart rate.
      Microinjection of histamine into the medial parvocellular subdivision (mp) of the
      PVN elicited a yawning response, i.e. a single large inspiration with mouth
      opening, and an arousal shift in ECoG to lower voltage and faster rhythms.
      Microinjection of HTMT dimaleate, an H1 receptor agonist, into the PVN also
      caused the yawning/arousal response. Pretreatment with pyrilamine, an H1 receptor
      antagonist, inhibited the histamine induced yawning behavior. These data
      demonstrate that a histamine receptive site for triggering yawning/arousal
      responses exists in the PVN, and suggest that these responses are mediated by
      activation of H1 receptor within the PVN.

PMID- 12191795
TI  - Kinematics of a coordinated goal-directed bimanual task.
AB  - The experiments address the problem of bimanual coordination in a familiar task
      of everyday life. A goal-directed drawer-pulling task, with asymmetrical
      assignments among hands, was analyzed with the objective to detect discrete
      kinematic events ('anchors') that potentially could serve in proper goal
      synchronization. The left hand reached out for the drawer and opened it while the
      right hand performed a prehension movement to pick up a peg from the drawer. The
      task was smoothly performed, independently of vision. Typically, trajectories and
      velocity profiles of the leading pull-hand were more stereotypical than the more
      variable ones of the pick-hand. The pull-hand had a large velocity peak during
      reaching, followed by a small peak during pulling. Velocity profiles of the pick
      hand were not bell-shaped and exhibited one or two broad waves, often with an
      irregular and probing evolution. Velocity profiles of both hands were aligned
      with the first or the second velocity peak of the leading pull-hand. In the
      majority of cases, temporal associations of events in the kinematics of the two
      limbs could thus be identified, which could serve to synchronize the hands at the
      goal. The nearly straight biphasic reach-and-pull trajectory of the leading hand
      contrasted with the more curved trajectory of the right pick-hand whereas, in the
      same unimanual action, the latter trajectories were quasi-rectilinear. Changing
      constraints (no vision, cutaneous anesthesia of pulling fingers) could change the
      coordination pattern. We argue that bimanual coordination relies on two
      interacting mechanisms: (1) feedforward control on the basis of sensorimotor
      memory; (2) temporal adjustments during the evolving bimanual synergy. Multiple
      strategies, imposed by the leading pull-hand, appeared to be responsible for
      feedback-induced corrections in the pick-hand and were found to contribute to the
      goal-invariance and to the principle of motor equivalence.

PMID- 12191796
TI  - Cholinergic receptor blockade in prefrontal cortex and lesions of the nucleus
      basalis: implications for allocentric and egocentric spatial memory in rats.
AB  - In this study we have examined the involvement of the prefrontal cortex (PFC)
      along with the Nucleus basalis magnocellularis (NBM) in two types of spatial
      navigation tasks. We evaluated the effects of excitotoxic (ibotenate-induced)
      lesions of the NBM in an allocentric and an egocentric task in the Morris water
      maze, using sham operations for a comparison. In both cases we also assessed the
      effects of local cholinergic receptor blockade in the PFC by infusing the
      muscarinic receptor antagonist scopolamine (4 or 20 microg). Anatomically, the
      results obtained showed that this lesion produced a profound loss of
      acetylcholinesterase (AChE) positive cells in the NBM, and a loss of AChE
      positive fibres in most of the neocortex, but hardly in the medial PFC.
      Behaviourally, such lesions led to a severe impairment in the allocentric task.
      Intraprefrontal infusions of scopolamine led to a short-lasting impairment in
      task performance when the high dose was used. In the second experiment, using the
      same surgical manipulations, we examined the performance in the egocentric task.
      Like in the allocentric task animals with NBM lesions were also impaired, but
      with continued training they acquired a level of performance similar to the sham
      operated ones. This time, infusions of scopolamine in the medial PFC led to a
      severe disruption of performance in both groups of animals. We conclude that
      acetylcholine in the medial PFC is important for egocentric but not allocentric
      spatial memory, whereas the NBM is involved in the learning of both tasks, be it
      to a different degree.

PMID- 12191797
TI  - Does hypertension alone lead to cognitive decline in spontaneously hypertensive
      rats?
AB  - Spontaneously hypertensive rats (SHR) represent an animal model of cognitive
      decline associated with hypertension. Few studies have systematically
      investigated this decline in aging. We assessed spatial learning performances of
      SHR, the genetically similar Wistar-Kyoto rats (WKY), and Sprague-Dawley rats
      (SD), in a water maze (WM) task. The following age ranges were studied: 6, 12,
      and 20 months. The results demonstrated that all three strains show the same
      level of impairment at the age of 20 months. The rate of cognitive decline,
      however, is different: both SHR and WKY show moderate degrees of impairment at
      all age ranges, while SD display good cognitive abilities at 6 months, declining
      at 12, and reaching the performance level of the other two groups at 20 months.
      Besides, the nine groups showed substantial differences in swim velocity and WKY
      exhibited a peculiar motor behavior. These results suggest the following: (a) the
      decline in cognitive level exhibits different trends in the three strains; (b)
      learning impairment of aged SHR might not be entirely explained by hypertension;
      (c) WKY should be used cautiously as normotensive control for SHR, due to their
      unusual behavior and low learning abilities; (d) analysis of escape distances is
      mandatory for the comparison of different strains in the WM test.

PMID- 12191798
TI  - Ventral tegmental lesions reduce overconsumption of normally preferred taste
      fluid in rats.
AB  - Previous studies have suggested that the brain regions along the taste pathway
      and its anatomical interfacing with the brain reward system are concerned with
      palatability-induced consumption. To clarify whether the ventral tegmental area
      (VTA) is involved in the behavioral expression induced by taste pleasantness, we
      examined the effects of lesions to the VTA on the consumption of taste stimuli in
      rats. (1) Bilateral extensive electrolytic lesions to the VTA selectively reduced
      the consumption of a normally preferred taste fluid (0.1 M sucrose) compared to
      that of sham-operated animals during a 24-h two-bottle choice test. The
      consumption of other fluids, including non-preferred taste fluids (HCl and
      quinine hydrochloride) was not different between the lesioned and sham animals.
      (2) The injection of midazolam (3 mg/kg), a benzodiazepine agonist, or morphine
      (2 mg/kg) significantly increased the consumption of 0.1 M sucrose fluids in the
      sham animals. The same injections, however, failed to increase intake of the 0.1
      M sucrose in rats with 6-hydroxydopamine lesions of the VTA. Neither midazolam
      nor morphine modified the intake of non-preferred quinine (0.0003 M) solution in
      both the lesioned and sham animals. These results suggest that dopaminergic
      mediation in the VTA is required to enhance the consumption of normally preferred
      fluids exclusively.

PMID- 12191799
TI  - Vestibular evoked potentials from the vertical semicircular canals in humans
      evoked by roll-axis rotation in microgravity and under 1-G.
AB  - Vestibular evoked potentials during rotation of human subjects around their naso
      occipital roll-axis were recorded. The effect of stimulating the vertical
      semicircular canals and otolithic stimulation was investigated by comparing the
      evoked potentials obtained under the 1-G condition with those recorded in
      microgravity conditions. Subjects lay on their side with the head in the center
      of rotation and were tilted feet upward (roll up) and back into the lying
      position (roll down). The microgravity environment was created by parabolic
      flight maneuvers. In microgravity, transient bell-shaped negativity was recorded
      for roll up and down motion. In the 1-G condition the potentials were
      superimposed on sustained components, probably due to additional otolithic
      stimulation. It seems to be possible to separate the evoked responses in a
      transient canal response and a sustained otolithic response. The results are
      encouraging with respect to the goal of developing a tool for the selective
      assessment of canal and otolithic responses of the vestibular system.

PMID- 12191800
TI  - Learning and memory in two different reward tasks in a radial arm maze in rats.
AB  - In an eight-arm radial maze, working and reference memory can be assessed
      simultaneously in the fixed position of reward task (FPRT) in which half of the
      arms are baited and their positions are fixed throughout the training trails. We
      characterized performance of rats in the variable position of reward task (VPRT),
      in which four out of eight arms were baited, but the positions were varied in
      every training trial. In the VPRT, the rats learned to choose all arms without
      any discrimination between baited and non-baited arms and the memory retention
      was time-dependent. The performance of rats in the FPRT was impaired by altering
      the spatial organization of the extramaze cues while it was not affected in the
      VPRT. The number of Fos-positive cells transiently increased in the cerebral
      cortex and hippocampus of both groups of animals during the training. Finally,
      bilateral lesions of the dorsal hippocampus resulted in an impairment of working
      memory in the FPRT and the performance of the rats in the VPRT. These results
      suggest that different strategies are used between the FPRT and VPRT but the
      hippocampus plays an important role in performance of rats trained for the VPRT
      as well as FPRT.

PMID- 12191801
TI  - Embryonic light stimulation induces different asymmetries in visuoperceptual and
      visuomotor pathways of pigeons.
AB  - In birds, visual object discrimination performance is lateralized with a
      dominance of the right eye/left hemisphere. This asymmetry is induced by
      embryonic light stimulation. However, visually guided behavior, even during
      simple object distinction tasks, is composed of different behavioral and neural
      modules. Therefore, the aim of the present study was to test whether all neural
      subsystems involved in visual discriminations are lateralized in a similar way
      after prehatch visual stimulation. To examine this question, two behavioral
      paradigms were used which reveal complementary aspects of visually guided
      behavior. The first was the grain-grit discrimination task in which no left-right
      differences in the number of pecks, but significant differences in the number of
      grains can be found. Therefore, grain-grit discrimination reveals visuoperceptual
      performance but not visuomotor speed. The contrary seems to be the case for a
      successive pattern discrimination with a VR32 schedule. Here, the hemispheres do
      not differ with respect to discrimination accuracy but with regard to the number
      of pecks emitted. Thus, successive pattern discrimination with lean VR schedules
      reveals hemispheric differences in visuomotor speed without testing
      visuoperceptual performance. Using these two paradigms a group of light and a
      group of dark incubated pigeons were tested. The results show that dark incubated
      birds evinced no asymmetry in any measure while light incubated ones were right
      eye dominant in both variables. However, light incubation induced a visual left
      hemispheric dominance by modulating two different processes, a left-hemispheric
      increase of visuoperceptual processes; and a right-hemispheric decrease for
      visuomotor speed. Taken together these data show that embryonic light stimulation
      elicits visual lateralization by differently modulating visuoperceptual and
      visuomotor systems in both hemispheres.

PMID- 12191802
TI  - Does neuropeptide Y contribute to the modulation of brain stimulation reward by
      chronic food restriction?
AB  - The rewarding effect produced by electrically stimulating particular sites in the
      lateral hypothalamus (LH) can be enhanced by chronic food restriction and body
      weight loss. The impact on brain stimulation reward (BSR) of certain hormones
      involved in the regulation of energy balance, such as leptin and corticotropin
      releasing hormone, depends upon the sensitivity of BSR to food restriction. The
      present investigation assessed the influence of neuropeptide Y (NPY), a potent
      orexigenic peptide, on BSR generated by stimulating restriction-sensitive and 
      insensitive sites in the LH. Twelve male Long Evans rats were trained to press a
      lever for a rewarding train of stimulation. Rate-frequency curves, reflecting the
      number of rewards earned as a function of the stimulation frequency, were
      collected during free-feeding and then again following a period of food
      restriction and 20-25% body weight loss. NPY (4 microg) was administered
      intraventriculary during the food restriction condition. Alterations in the
      rewarding effect of the stimulation were assessed by measuring changes in the
      frequency required to maintain half-maximal rewards earned (M-50). In half of the
      subjects, food restriction produced significant decreases in M-50 values,
      indicating that the reward effectiveness of the stimulation was potentiated. In
      contrast, M-50 values were unaltered by food restriction in the remaining six
      animals. In most of the subjects in which M-50 values decreased following chronic
      food restriction, NPY failed to alter BSR. Similarly, BSR was unchanged by NPY
      administration in most of the rats with restriction-insensitive stimulation
      sites. These findings suggest that NPY does not take part in the process whereby
      food restriction and leptin modulate reward circuitry activated by stimulating
      restriction-sensitive sites.

PMID- 12191803
TI  - Olfactory sensitivity for aliphatic esters in squirrel monkeys and pigtail
      macaques.
AB  - Using a conditioning paradigm, the olfactory sensitivity of four squirrel monkeys
      and three pigtail macaques for a homologous series of aliphatic esters (ethyl
      acetate to n-octyl acetate) and isomeric forms of some of these substances were
      investigated. With only few exceptions, all animals of both species significantly
      discriminated concentrations below 1 ppm from the odorless solvent, and in
      several cases, individual monkeys even demonstrated thresholds below 1 ppb. The
      results showed (a) both primate species to have an unexpectedly high olfactory
      sensitivity for aliphatic esters, which for the majority of substances matches or
      even is better than that of species such as the rat, the mouse, or the dog; (b)
      squirrel monkeys to generally perform better than pigtail macaques in detecting
      aliphatic esters; and (c) a significant negative correlation between
      perceptibility in terms of olfactory detection thresholds and carbon chain length
      of the n-aliphatic esters in both species tested. These findings support the
      assumptions that between-species comparisons of neuroanatomical features are a
      poor predictor of olfactory performance and that general labels such as
      'microsmat' or 'macrosmat'--which are usually based on allometric comparisons of
      olfactory brain structures--are inadequate to describe a species' olfactory
      capabilities.

PMID- 12191805
TI  - Differential effects of environmental enrichment on behavior and learning of male
      and female Ts65Dn mice, a model for Down syndrome.
AB  - We have assessed the effects of enriched environment (EE) upon behavioral and
      cognitive performances of partially trisomic Ts65Dn (TS) mice and their control
      (CO) littermates. Enriched environment was applied to pups for 7 weeks after
      weaning. Circadian spontaneous activity (actimetry), exploratory behavior (hole
      board), activity in the open field and spatial memory (Morris Water Maze,
      repeated acquisition and cued paradigms) were analyzed in 86 female and 75 male
      mice, starting 15 days after completing enrichment. For each gender, mice were
      distributed in non-enriched and enriched control and trisomic groups. Enriched
      environment reduced in trisomic females and enhanced in trisomic males' circadian
      activity. Exploratory behavior was increased by enrichment in all groups,
      regardless of gender or presence of trisomy. In the Morris Water Maze, a
      significant improvement of the spatial memory was observed in enriched-control
      females, but not in enriched-control male mice, as assessed by distances
      traveled. Performances in the four groups of control animals were also
      consistently and significantly better than those of matching trisomic mice. In
      the acquisition trials, enrichment improved performance in trisomic female
      animals, but deteriorated in trisomic male mice. In all groups, changes in escape
      latencies and distances induced by enrichment were accounted for by changes in
      the total time spent in the periphery of the pool, indicating changes in learning
      strategy. Working memory was the function more affected by enrichment. It is
      concluded that enriched environment induces behavioral and learning changes in
      trisomic mice, although gender plays a significant modulatory role.

PMID- 12191804
TI  - Participation of the lateral septal nuclei (LSN) in the antidepressant-like
      actions of progesterone in the forced swimming test (FST).
AB  - The possible participation of lateral septal nuclei (LSN) in the antidepressant
      like actions of progesterone was evaluated. The effect of different
      concentrations of progesterone (0.001, 0.01 and 0.1 M) or saline solution
      injected directly into the LSN of ovariectomised rats was determined using the
      forced swimming test (FST). In addition, the temporal course of progesterone (0.1
      M) antidepressant-like actions was compared with that of the classical
      antidepressant imipramine (0.1 M). Finally, in order to establish the possible
      participation of the GABA(A) receptor in the antidepressant-like action of
      progesterone, the effect of pre-treatment with the GABA(A) antagonist picrotoxin
      (0.125 mg/kg, i.p.) was evaluated. Intraseptally administered progesterone
      produced a concentration-dependent decrease in immobility behaviour but did not
      modify locomotor activity. These antidepressant-like actions lasted 4 h, while
      those of imipramine lasted 72 h. Finally, progesterone-induced anti-immobility
      effect could be blocked by the systemic injection of picrotoxin. Present results
      reveal that LSN play a role in the antidepressant-like actions of progesterone
      that appear to be mediated by the GABA(A) receptor.

PMID- 12191806
TI  - Reduced prepulse inhibition in rats with entorhinal cortex lesions.
AB  - The relationship between the entorhinal cortex and prepulse inhibition (PPI) as
      well as dopaminergic participation in this relationship were examined. PPI is an
      operational measure of sensorimotor gating in which a robust response to a
      startling auditory pulse stimulus is inhibited when the stimulus is preceded by a
      weak prepulse. PPI can be measured in various species and is reduced in several
      neuropsychiatric disorders and in dopamine-activated rats. The entorhinal cortex
      was damaged bilaterally using ibotenic acid, and acoustic startle experiments
      were performed during treatment with haloperidol or saline on day 21 after the
      ibotenic acid injection. Neither this injection nor haloperidol affected the
      amplitude of the startle movement. Bilateral entorhinal cortex lesions reduced
      PPI, while haloperidol partially restored it. The entorhinal cortex and the
      sensorimotor gating system therefore may be related via dopaminergic circuits,
      possibly including the nucleus accumbens. Further, as the entorhinal cortex
      provides the major extrinsic synaptic input to the rat hippocampus, disease
      involvement of this region may severely affect cognition in various disorders
      including schizophrenia.

PMID- 12191807
TI  - Does order and timing in performance of imagined and actual movements affect the
      motor imagery process? The duration of walking and writing task.
AB  - The purpose of the present study was to investigate the effects on the duration
      of imagined movements of changes in timing and order of performance of actual and
      imagined movement. Two groups of subjects had to actually execute and imagine a
      walking and a writing task. The first group first executed 10 trials of the
      actual movements (block A) and then imagined the same movements at different
      intervals: immediately after actual movements (block I-1) and after 25 min (I-2),
      50 min (I-3) and 75 min (I-4) interval. The second group first imagined and then
      actually executed the tasks. The duration of actual and imagined movements,
      recorded by means of an electronic stopwatch operated by the subjects, was
      analysed. The duration of imagined movements was very similar to those of actual
      movements, for both tasks, regardless of either the interval elapsed from the
      actual movements (first group) or the order of performance (second group).
      However, the variability of imagined movement duration was significantly
      increased compared to variability of the actual movements, for both motor tasks
      and groups. The findings give evidence of similar cognitive processes underlying
      both imagination and actual performance of movement.

PMID- 12191808
TI  - An examination of the effects of bilateral excitotoxic lesions of the
      pedunculopontine tegmental nucleus on responding to sucrose reward.
AB  - The effects of bilateral excitotoxic lesions of the pedunculopontine tegmental
      nucleus (PPTg) on sucrose intake were examined in three experiments. First, in
      tests of conditioned place preference using 20% sucrose as the reinforcer, it was
      shown that lesioned rats, regardless of whether they were food deprived or non
      deprived, formed normal place preferences and showed normal amounts of
      locomotion. However, consumption of 20% sucrose in the pairing trials was
      increased in the deprived PPTg lesioned rats compared to their matched controls.
      A second experiment showed that sucrose consumption in the home cage was
      increased in both deprived and non-deprived PPTg lesioned rats, but only when the
      concentration of sucrose was greater than 12%: below this there were no
      differences in intake between the lesioned and control rats. In a third home cage
      experiment, it was again shown that non-deprived PPTg lesioned rats increased
      their consumption of 20% sucrose compared to controls. PPTg lesioned rats
      concomitantly reduced their intake of lab chow such that overall energy intake
      remained the same as that of control rats. These data are taken to suggest (i)
      that bilateral excitotoxic lesions of the PPTg increase consumption of sucrose
      selectively in conditions of high motivational excitement; (ii) that the
      perception of the rewarding value of 20% sucrose, as judged by place preference,
      is not affected by these lesions; and (iii) that PPTg lesioned rats are able to
      adjust their energy intake to accommodate increased sucrose loads. These data are
      consistent with the hypothesis that bilateral excitotoxic lesions of the PPTg do
      not affect energy balance regulation or judgment of the hedonic value of sucrose,
      but that they do affect the control of responding in the face of high levels of
      motivational excitement.

PMID- 12191809
TI  - Influence of acute or repeated restraint stress on morphine-induced locomotion:
      involvement of dopamine, opioid and glutamate receptors.
AB  - The development of restraint stress-induced sensitization to the locomotor
      stimulating effect of morphine (2 mg/kg i.p.) was investigated. In experiment 1,
      both a single restraint session (2 h) and a repeated restraint stress (2 h per
      day for 7 days), similarly enhanced the effects of morphine on motor activity. In
      experiment 2, we observed that this sensitization was prevented by administration
      of both D(1) and D(2) dopaminergic antagonist [SCH-23390 (0.5 mg/kg i.p.) and (+/
      )-sulpiride (60 mg/kg i.p.)] 10 min prior to the stress session. In experiment 3,
      we showed that an opioid antagonist pretreatment [naltrexone (1 mg/kg i.p.) 10
      min prior to stress session, suppressed the stress-induced sensitization after
      morphine administration. In experiment 4, pretreatment with a non-competitive
      antagonist of the N-methyl-D-aspartate (NMDA) type of glutamate receptors [(+)-MK
      801 (0.1 mg/kg i.p.)], 30 min prior to the acute restraint session, prevented the
      development of sensitization to morphine. All these results suggest that: (1)
      sensitization to morphine on stimulating locomotor effect does not depend on the
      length of exposure to stress (acute vs. repeated); (2) stimulation of both D(1)
      and D(2) dopaminergic receptors is necessary for the development of restraint
      stress-induced sensitization to morphine; (3) an opioid system is also involved
      in this sensitization process; and (4) the stimulation of glutamatergic NMDA
      receptors is involved in this acute restraint-induced effect.

PMID- 12191810
TI  - Enhanced antidepressant effect of sigma(1) (sigma(1)) receptor agonists in
      beta(25-35)-amyloid peptide-treated mice.
AB  - This study examined the antidepressant efficacy of the selective sigma(1)
      receptor agonists igmesine or PRE-084 in mice injected intracerebroventricularly
      (i.c.v.) with beta(25-35)-amyloid peptide and submitted to the forced swim test.
      Beta(25-35) peptide-injected animals developed memory deficits after 8 days
      contrarily to controls injected with scrambled beta(25-35) peptide or vehicle
      solution. In the forced swim test, the i.c.v. treatment failed to affect the
      immobility duration, but the antidepressant effect of the sigma(1) agonists was
      facilitated in beta(25-35) animals. Igmesine reduced immobility duration at 30
      versus 60 mg/kg in control groups. PRE-084 decreased immobility duration at 30
      and 60 mg/kg only in beta(25-35) animals. Desipramine reduced the immobility
      duration similarly among groups and fluoxetine appeared less potent in beta(25
      35) animals. The beta(25-35) animals exhibited decreased progesterone levels in
      the hippocampus (-47%). The behavioural efficacy of sigma(1) agonists is known to
      depend on neuro(active)steroids levels synthesised by glial cells and neurones,
      which are affected by the beta-amyloid toxicity. This behavioural study suggests
      that sigma(1) agonists, due to their enhanced efficacy, may allow to alleviate
      the depressive symptoms associated with Alzheimer's disease.

PMID- 12191811
TI  - Blockade of sensitisation-induced facilitation of appetitive conditioning by post
      session intra-amygdala nafadotride.
AB  - Prior D-amphetamine experience has been reported to enhance appetitive Pavlovian
      conditioning. The present study assessed the involvement of the mesoamygdaloid
      dopamine projection in this effect. Bilateral post-session intra-amygdala
      infusions of the D3 dopamine receptor antagonist, L-nafadotride, or vehicle were
      given during acquisition of a Pavlovian association in sensitised and
      unsensitised rats. During these sessions, subjects received presentations of a
      stimulus (CS(+)) paired with 10% sucrose availability. A second stimulus (CS(-))
      was also presented but never paired with sucrose. Sensitised animals infused post
      session with vehicle acquired a Pavlovian conditioned approach response during
      CS(+) presentations more rapidly than controls, as we have shown previously.
      However, post-session intra-amygdala L-nafadotride selectively retarded
      conditioned responding to the CS(+) in both groups of animals, abolishing the
      difference between sensitised and unsensitised rats. These results, therefore,
      extend the evidence for the involvement of the mesoamygdaloid dopamine projection
      in Pavlovian conditioning, and the facilitation of associative learning following
      sensitisation.

PMID- 12191812
TI  - Mecamylamine blocks enhancement of reference memory but not working memory
      produced by post-training injection of nicotine in rats tested on the radial arm
      maze.
AB  - The focus of this study was to analyze whether the psychostimulant nicotine would
      enhance reference and working memory consolidation in rats tested on the 8-arm
      radial arm maze. Mecamylamine, a nicotine antagonist, was used to attempt to
      block the enhancement of memory consolidation. All rats were given one training
      trial/day for 12 consecutive days, and 4 arms were baited. Rats were separated
      into five groups: the saline-nicotine group received an intraperitoneal (i.p.)
      injection of saline immediately after each trial followed 15 min later by an
      subcutaneous (s.c.) injection of nicotine (0.6 mg/kg free base); the nicotine
      delay group received an s.c. injection of nicotine 2 h after each training trial,
      two groups received an i. p. injection of one of two different doses of
      mecamylamine (2.5 and 6.0 mg/kg) immediately after each trial, which was followed
      15 min later by an s.c. nicotine injection, and a control group received an i.p.
      injection of saline immediately and 15 min after each training trial. Results
      showed that the saline-nicotine group made fewer reference and working memory
      errors than the saline- or nicotine-delay groups, but only the effect of nicotine
      on reference memory was blocked by the higher dose of mecamylamine. It appears
      from these results that nicotine's effects on reference and working memory may be
      mediated through different mechanisms.

PMID- 12191813
TI  - Effects of repeated treatment with amphetamine or phencyclidine on working memory
      in the rat.
AB  - Repeated exposure to psychomotor stimulants produces long-lasting molecular,
      cellular and locomotor behavioral changes. Such changes are likely to contribute
      to the development of drug addiction and psychosis. It is not clear whether these
      durable changes are accompanied by lasting changes in cognition. We examined the
      long-term effects of repeated treatment with phencyclidine (PCP) or amphetamine
      on working memory, using a discrete, paired-trials, delayed-alternation task
      sensitive to the acute effects of PCP and amphetamine, and to the integrity of
      the prefrontal cortex. Twice daily treatment with PCP (5.0 mg/kg) or amphetamine
      (2.5 mg/kg) for 5 days did not produce lasting, significant impairments in
      alternation performance in comparison to either pre-treatment baseline
      performance or to the vehicle-treated group. Subsequent challenge doses of PCP
      (1, 3 and 5 mg/kg) produced alternation deficits in vehicle, PCP, and amphetamine
      pre-treated groups that were dependent on dose, but not on pre-treatment regimen.
      However, rats pre-treated with PCP showed a trend towards sensitization in
      response to PCP challenge. The present data suggest that psychostimulant
      treatment regimens that are reported to produce long-lasting changes in neural
      morphology and locomotor behavior may not produce equally durable changes in
      working memory.

PMID- 12191814
TI  - Subthalamic locomotor region is involved in running activity originating in the
      rat ventromedial hypothalamus.
AB  - We have previously shown the involvement of the ventromedial nucleus of the
      hypothalamus (VMH) in inducing running behavior. Stimulation of kainate (KA)-type
      glutamate receptors in the unilateral VMH of the rat exclusively elicited
      stereotyped running behavior. However, the neural pathways or functional
      connections of the VMH neurons involved in the running activity are yet to be
      elucidated further. In this study we examined whether the subthalamic locomotor
      region (SLR) is involved in the expression of the running activity originating in
      the VMH. The multiunit activity (MUA) in the ipsilateral SLR was significantly
      increased by KA injection into the VMH of urethane-anesthetized animals.
      Concomitant injection of 6,7-dinitroquioxalline-2,3-dione (DNQX, a KA-type
      glutamate receptor antagonist) with KA blocked this change in the MUA. Unilateral
      pre-injection of either kynurenate (non-selective glutamate receptor antagonist),
      D-2-amino-5-phosphonovalerate (AP5, an NMDA-type glutamate receptor antagonist)
      or DNQX into the SLR blocked the expression of the running activity induced by KA
      injection into the ipsilateral VMH. Results from the present study suggest that
      communication between KA-sensitive efferents from the VMH to glutamatergic
      pathways acting via NMDA and non-NMDA receptors in the SLR may underlie
      expression of running behavior originating in the VMH.

PMID- 12191815
TI  - Restricted feeding facilitates time-place learning in adult rats.
AB  - Many species can acquire time-of-day discrimination when tested in food
      reinforced place learning tasks. It is believed that this type of learning is
      dependent upon the ability of animals to consult their internal circadian
      pacemakers entrained by various environmental zeitgebers, such as light-dark
      cycles and scheduled restricted feeding. In the present study, we examined, (1)
      whether rats can acquire time-of-day discrimination in an aversively motivated
      water maze task wherein an escape platform is located in one position in the
      morning and in another position in the afternoon; (2) whether time-of-day cues
      provided by the light- and feeding-entrainable pacemakers may have divergent
      impacts upon the ability of rats to learn this task. Two groups of rats, both
      maintained on 12-h light:12-h dark cycle, were used; in one group, animals had
      free access to food, whereas in the other, they were subjected to a restricted
      feeding protocol (60% of food consumed by rats fed ad libitum, once daily).
      Despite the heightened difficulty of the task, food-restricted rats were
      apparently able to acquire associations between two different platform positions
      and two different times of day, as indicated by the fact that the percentage of
      discrimination errors in this group declined progressively, as a function of
      training, and stabilized at the level of 22+/-9%. In contrast, rats that were fed
      ad libitum, even after extensive training, failed to perform the task above level
      of chance. These data indicate that time-place learning is a universal, reward
      nonspecific, cognitive phenomenon. They furthermore suggest that the ability of
      animals to integrate spatial and temporal information can be dependent on the
      access to timing stimuli provided by the feeding-entrainable circadian system.

PMID- 12191816
TI  - Memory for context is impaired by a post context exposure injection of
      interleukin-1 beta into dorsal hippocampus.
AB  - Prior research has revealed that treatments that elevate the level of the pro
      inflammatory cytokine IL-1beta in the brain, if given after training, impair
      contextual but not auditory-cue fear conditioning. The present experiments add to
      these finding by showing that, (a) IL-1beta exerts its effect on contextual fear
      conditioning by impairing consolidation processes that support the storage of the
      memory representation of the context; (b) the dorsal hippocampus is a critical
      site for the effect of IL-1beta; (c) the effect of IL-1beta cannot be attributed
      to its effect on glucocorticoid levels; and (d) IL-1beta injected into dorsal
      hippocampus either, immediately, 3, or 24 h, but not 48 h, after training
      produces this impairment. At this time the mechanisms responsible for this
      impairment are not understood, but may involve late-phase protein synthesis
      processes associated with LTP, because later consolidation processes are being
      disrupted.

PMID- 12191817
TI  - Memory for context is impaired by injecting anisomycin into dorsal hippocampus
      following context exploration.
AB  - Pre-exposure to the context facilitates the small amount of contextual fear
      conditioning that is normally produced by immediate shock. This context pre
      exposure facilitation effect provides a convenient way to study the rat's
      learning about context. We recently reported that anterograde damage to dorsal
      hippocampus prevents this facilitation. The present experiments strengthen this
      conclusion by showing that the protein synthesis inhibitor, anisomycin, injected
      bilaterally into the dorsal hippocampus following context pre-exposure also
      significantly reduces the facilitation effect. The same treatment given
      immediately after immediate shock, however, had no effect on facilitation. These
      results support theories that assume that, (a) contextual fear involves two
      processes, acquiring and storing a conjunctive representation of a context and
      associating that representation with fear; and (b) the hippocampus contributes to
      contextual fear by participating in the storage of the memory representation of
      the context.

PMID- 12191818
TI  - Cholinergic activation of the basolateral amygdala regulates unlearned freezing
      behavior in rats.
AB  - Recent evidence suggests that the basolateral amygdala (BLA) is involved in the
      expression of freezing behavior in rats. This study investigated the effects of
      unilateral phthalic acid (PA) lesions of the nucleus basalis magnocellularis
      (NBM) on fear-motivated behavior in response to a natural predator-stimulus. Such
      lesions preferentially disrupt the cholinergic projection to the BLA. Rats were
      placed in a chamber containing either real or fake cat hair, and the amount of
      time spent freezing and the number of contacts made with the stimulus were
      measured. Compared with Sham control rats, the PA NBM-lesioned rats displayed
      significantly less freezing in the presence of the cat hair. Both the Sham and
      lesioned rats made fewer contacts with the real than the fake cat hair. Pre
      testing intra-BLA infusion of the direct muscarinic cholinergic agonist
      oxotremorine ipsilateral to the PA NBM-lesion attenuated the freezing deficit.
      The indirect non-specific cholinergic agonist physostigmine increased the time
      spent freezing in Sham rats, but did not attenuate the freezing deficit in the
      NBM-lesioned rats. Sham and NBM-lesioned rats given oxotremorine infusions made
      fewer contacts with either the real or the fake cat hair. The PA NBM-lesion did
      not affect open field activity. These findings indicate that muscarinic
      cholinergic activation in the BLA from the NBM influences fear-motivated freezing
      behavior.

PMID- 12191819
TI  - Discrimination of morphine- and haloperidol-induced muscular rigidity and
      akinesia/catalepsy in simple tests in rats.
AB  - The present study was conducted to establish a simple method for measuring
      muscular rigidity in rats, which could be used for screening and is able to
      discriminate between rigidity and akinesia/catalepsy. Therefore, we treated rats
      with morphine (30 mg/kg i.p.), since large doses of morphine lead to muscular
      rigidity and akinesia. We measured muscular rigidity with a new method by
      determining the resistance of the hindlimb to passive flexion in the 'balance
      test' and also checked haloperidol (3 mg/kg i.p.) treated rats for muscular
      rigidity. Furthermore, catalepsy was also tested after administration of each of
      these drugs. Then, the influence of D(1)-like and D(2)-like dopamine receptor
      stimulation on muscular rigidity and catalepsy was studied. Therefore, the
      partial D(1) agonist SKF 38393 (3 and 8 mg/kg s.c.), the D(2)/D(1) agonist
      pergolide (0.25 and 0.5 mg/kg i.p.) and the dopamine precursor L-DOPA (50 and 100
      mg/kg i.p.) were administered up to 30 min before muscular rigidity was measured
      in morphine-treated rats. The results showed that morphine, but not haloperidol
      led to muscular rigidity, whereas both drugs led to positive scores in the
      catalepsy test. The dopaminergic drugs partly antagonized the morphine-induced
      muscular rigidity in the doses applied, but not the catalepsy. Apparently,
      rigidity, akinesia/catalepsy produced by morphine can be discriminated from that
      produced by haloperidol in simple and quick tests.

PMID- 12191820
TI  - Absence of impairments or recovery mediated by the uncrossed pyramidal tract in
      the rat versus enduring deficits produced by the crossed pyramidal tract.
AB  - The pyramidal tract of the rat consists of at least two components. A majority of
      the fibers cross in the lower medulla and descend through the spinal cord in the
      ventral portion of the dorsal funiculus. The remaining 5% of the corticospinal
      projection does not cross and descends in the ipsilateral ventral funiculus into
      the cervical spinal region where its projections terminate in the internuncial
      portions of the spinal gray matter. The anatomical origin and terminal
      distribution of the ipsilateral component suggests that it may be involved in the
      control of the ipsilateral limb, but the possible contribution of the ipsilateral
      corticospinal tract has not been systematically examined. To determine whether
      the ipsilateral corticospinal tract makes a contribution to skilled movement, the
      corticospinal tract was severed unilaterally at the medullary level rostral to
      the decussation, thus severing both the crossed component of the tract as well as
      the ipsilateral component. Performance of the ipsilateral and the contralateral
      limbs of rats were then evaluated on tests of limb posture, preference, placing,
      and use in two skilled reaching tasks. No impairments on any quantitative or
      qualitative measure of performance were detected in the use of the limb
      ipsilateral to the lesion but severe, enduring impairments on all qualitative and
      quantitative measures were obtained in use of the limb contralateral to the
      lesion. Thus, the study finds: (1) no evidence that the ipsilateral portion of
      the corticospinal tract makes a contribution to skilled movement of the kind made
      by the contralateral portion of the corticospinal tract, and (2) no evidence that
      the remaining uncrossed portion of the tract contributes to recovery of symptoms
      produced by severing the crossed portion of the tract.

PMID- 12191821
TI  - The selective serotonin(1A)-receptor antagonist WAY 100635 blocks behavioral
      stimulating effects of cocaine but not ventral striatal dopamine increase.
AB  - An increase in the extracellular dopamine (DA) concentration is generally
      accepted as an important neurochemical mediator of the behavioral effects of
      cocaine. Cocaine induced increases in serotonergic (5-HT) activity also appears
      to be involved in these effects. Here we describe the effects of the 5-HT(1A)
      receptor antagonist WAY 100635 on the behavioral and neurochemical effects of
      cocaine. In-vivo microdialysis was used in behaving rats to measure extracellular
      concentration of DA in the nucleus accumbens (Nac). Four groups of animals
      received one of the following drug combinations: WAY 100635 (0.4 mg/kg) and
      cocaine (10 mg/kg), saline and cocaine (10 mg/kg), WAY 100635 (0.4 mg/kg) and
      saline, or saline and saline. The injections were administered i.p. and spaced 20
      min apart. The pretreatment with WAY 100635 significantly attenuated the
      locomotor stimulant effects of cocaine without altering the DA overflow in the
      Nac. WAY 100635 itself did not modify locomotion or the extracellular DA
      concentration in the Nac. These results indicate that (1) the 5-HT(1A)-receptor
      is an important component in the mediation of cocaine locomotor stimulant
      effects, and (2) an increase in the extracellular DA concentration in the Nac
      might be a necessary but is not a sufficient condition for the locomotor
      stimulant effects of cocaine.

PMID- 12191822
TI  - Neurochemical changes in mice following physical or psychological stress
      exposures.
AB  - An investigation on the mechanism of neurochemical changes in physically or
      psychologically stressed mice was carried out. Physical stress was induced by
      electric foot shocks (2 mA for 5 s at 30-s intervals), and psychological stress
      was induced by emotional stimuli from electric foot-shocked mice using a
      communication box. The serum and brain calcium levels and immunohistochemical
      brain dopamine levels increased, and the ethanol-induced sleeping time was
      prolonged following exposure to these stimuli. The effects of electric foot
      shocks on these physiological parameters were greater than those of emotional
      stimuli. In the psychologically stressed mice, serum and brain calcium levels
      significantly increased 15 and 60 min, respectively, after the start of exposure
      to stimuli. Also, the immunohistochemical dopamine levels in the neostriatum and
      nucleus accumbens regions after 60 min of exposure to psychological stress were
      higher by 23% (P < 0.01) and 27% (P < 0.01), respectively, than those in
      unstressed control mice. Moreover, the ethanol-induced sleeping time was
      prolonged by approximately 60-100% (P < 0.01) in mice exposed to psychological
      stress for 30-120 min. The effect of emotional stimuli to prolong the ethanol
      induced sleeping time was inhibited by intracerebroventricular administration of
      W-7 (a calmodulin antagonist) or alpha-methyltyrosine (an inhibitor of tyrosine
      hydroxylase). In light of previous reports that calcium activates dopamine
      synthesis in the brain via a calmodulin-dependent system, it is suggested that
      physical or psychological stimuli induce an increase in the brain calcium level,
      and this increased calcium level in turn enhances dopamine synthesis in the
      brain. Subsequently, an increased dopamine level induces various physiological
      changes related to stress-dependent phenomena.

PMID- 12191823
TI  - Niche-related learning in laboratory paradigms: the case of maze behavior in
      Norway rats.
AB  - The general hypothesis underlying this paper is that behavior in traditional
      paradigms of laboratory learning is based on niche-related mechanisms. The
      specific hypothesis is that the behavior of Norway rats in laboratory mazes is
      based on niche-related mechanisms related to trail following and navigating. I
      evaluate seven types of evidence for this hypothesis: (a) resemblance of maze
      behavior to behavior in unconstrained settings; (b) importance of experimenter
      tuning of apparatus and procedures; (c) overdetermination of laboratory behavior;
      (d) reverse-engineering of niche-related mechanisms from laboratory data; (e)
      prediction of laboratory results from ecological data; (f) contribution of
      specific relative to general mechanisms; and (g) phylogenetic conservation and
      ecologically-based convergence and divergence of maze mechanisms. I conclude
      there is strong evidence for the hypothesis that behavior of rats in laboratory
      mazes is based on niche-related mechanisms. I suggest that a niche-related
      approach to laboratory learning paradigms has conceptual generality and the
      potential to facilitate connections with the study of neurophysiology, genetics,
      and evolution.

PMID- 12191824
TI  - Prehatching visual experience and lateralization in the visual Wulst of the
      chick.
AB  - We revealed functional lateralization of the chick visual system by placing
      injections of monosodium glutamate (0.5 microl, 100 mM) into the left or right
      Wulst regions of the hemispheres, and examined the effects of light experience
      before hatching on this lateralization. Following exposure of the left or right
      eye to light for 24 h beginning on day 18 of incubation, the chick's ability to
      categorize grain as distinct from pebbles was impaired by glutamate treatment of
      the Wulst contralateral to the exposed eye. Attack and copulation scores were
      also elevated. Following incubation of the eggs in darkness or with both eyes
      exposed to light, treatment of neither the left or right Wulst affected
      performance on the pebble-grain task: showing that either the left and right
      Wulst can assume control of this function. Treatment of either the left or right
      Wulst of these chicks elevates attack and copulation. However, examination of the
      distribution of attack scores revealed a bimodality in the attack scores of the
      chicks treated with glutamate in the right Wulst and not those treated in the
      left Wulst. In summary, light stimulation of one eye during a critical period of
      embryonic development causes the visual Wulst contralateral to the light exposed
      eye to develop dominance over its equivalent region in the other hemisphere.
      Without this lateralized stimulation of light both the left and right Wulst
      regions are largely but not exactly equivalent.

PMID- 12191825
TI  - Blockade of alpha1 adrenoreceptors in the dorsal raphe nucleus prevents enhanced
      conditioned fear and impaired escape performance following uncontrollable
      stressor exposure in rats.
AB  - Previous research has shown that the effect of exposure to uncontrollable
      stressors on conditioned fear responding and escape behavior in rats is dependent
      on serotonergic neural activity in the dorsal raphe nucleus (DRN). The role that
      norepinephrine released in the DRN plays in producing the behavioral consequences
      of exposure to inescapable tail shock in rats was investigated in the present
      study. The selective alpha1 adrenoreceptor antagonist benoxathian was injected
      into the DRN before exposure to inescapable tail shock or before behavioral
      testing conducted 24 h later. Benoxathian prevented the impairment of escape
      responding produced by inescapable shock, but did not reverse this effect when
      given before testing. The enhancement of conditioned fear produced by prior
      inescapable shock was attenuated by benoxathian administered before inescapable
      shock or before behavioral testing. These results support the view that
      noradrenergic input to the DRN is necessary to produce the behavioral effects of
      inescapable tail shock.

PMID- 12191826
TI  - Cueing unavoidable physical but not emotional stress increases long-term
      behavioural effects in rats.
AB  - Cueing a stressor can influence the perception of and the direct reaction to a
      stressor. Until now, only the direct reaction of an animal to the cue or to the
      subsequent stressor has been examined. This experiment assesses the long-term
      behavioural effects of cueing two different stressors. Rats were exposed to
      physical stress (PS) or emotional stress (ES) in a two-compartment box for 5
      consecutive days. PS rats daily received mild foot shocks during 10 min. ES rats
      were forced to witness the PS rats being foot shocked. A control group was placed
      in the same box without receiving shocks. Every foot shock was either cued or not
      cued with a 3-s light signal. In an additional experiment the effect of longer
      and stronger foot shocks was also investigated. Effects of stress treatments were
      measured 5 days after the last stress session in a small open field. Data showed
      that PS and ES had opposite long-term effects on open field activity (activity PS
      decreased and ES increased). Cueing stress resulted in a more pronounced effect
      in the PS, but not in the ES group. Presenting the light signal during emotional
      stress and control treatment resulted in an overall behavioural activation in the
      open field. All animals were exposed to the light stimulus in an open field after
      habituation. Both PS groups showed less active exploration during the test, while
      all cue-naive animals showed more ambulations. No emotional stress effect was
      present. The direct reaction of the animals to the cue also differed with
      treatment: cued PS animals became inactive, while animals of all other groups
      primarily reacted with active exploration. Increasing the intensity of the foot
      shocks resulted in an increased physical stress effect, similar to cued physical
      stress; no effect was found on emotional stress effects. The results indicated
      that stress associated cues can increase the long-term behavioural effects of
      physical but not of emotional stress. Exposure to the cue induces a conditioned
      response in the cued PS group. Witnessing cued or more severe stressors did not
      influence the emotional stress effect. The findings again demonstrate that
      emotional and physical stressors are fundamentally different.

PMID- 12191827
TI  - Effects of (+/-) 3,4-methylene-dioxymethamphetamine (ecstasy) on dopamine system
      function in humans.
AB  - Twelve (+/-) 3,4-methylenedioxymethamphetamine (MDMA) users, who did not show
      other drug dependencies or prolonged alcohol abuse (group A), and 12 control
      subjects (group B) were included in the study. Prolactin (PRL) and growth hormone
      (GH) responses to the dopaminergic agonist bromocriptine (BROM) and psychometric
      measures were evaluated 3 weeks after MDMA discontinuation. PRL decreased both in
      A and B subjects after BROM suppression, without any significant difference
      between the two groups. PRL responses to BROM in MDMA users were in the normal
      range. In contrast, GH responses to BROM stimulation were found significantly
      reduced in ecstasy users, in comparison with control subjects (P < 0.001; F =
      6.26). MDMA users showed higher scores on the Novelty Seeking (NS) scale at the
      Three dimensional Personality Questionnaire (TPQ), on direct aggressiveness
      subscale at Buss Durkee Hostility Inventory (BDHI), on subscale D (depression) at
      Minnesota Multiphasic Personality Inventory (MMPI 2) and on Hamilton Depression
      Rating Scale (HDRS) than control subjects. PRL areas under the curves (AUCs)
      showed a significant inverse correlation with NS scores both in A and B subjects.
      GH AUCs directly correlated with NS scores in healthy subjects, but not in MDMA
      users. No other psychometric measure correlated with hormonal responses. GH AUCs
      were inversely correlated with the measures of MDMA exposure (r = -0.48; P <
      0.01). Lower GH response to BROM in A subjects (MDMA users) could reflect reduced
      D2 receptor sensitivity in the hypothalamus, possibly due to increased
      intrasynaptic dopamine concentration. Although the hypothesis of dopaminergic
      changes associated with a premorbid condition cannot be completely excluded, the
      inverse correlation between DA receptors sensitivity and the extent of ecstasy
      exposure may suggest a direct pharmacological action of MDMA on brain dopamine
      function in humans.

PMID- 12191828
TI  - The role of lateral septal NK1 receptors in mediating anxiogenic effects induced
      by intracerebroventricular injection of substance P.
AB  - The lateral septal nucleus (LS) presents a dense plexus of fibers containing
      substance P (SP), which is known to induce pronounced anxiogenic-like effects
      when applied into this brain site. In the present report, we investigated the
      role of lateral septal NK(1) receptors in mediating the pro-aversive effects
      resulting from intracerebroventricular (i.c.v.) injection of SP in rats observed
      in the elevated plus-maze (EPM) test. Our results show that FK888, a selective
      NK(1) receptor antagonist, injected into the LS inhibited the anxiogenic-like
      responses induced by SP i.c.v. injections, whereas the treatment with FK888 into
      the LS did not alter 'per se' the parameters recorded in the EPM test when
      compared to the control group that received physiological buffer solution into
      the LS and lateral ventricle. Thus, our data suggest that the anxiogenic-like
      responses induced by SP centrally injected are, to a large extent, mediated by
      NK(1) receptors in the LS.

PMID- 12191829
TI  - Frogs and toads in front of a mirror: lateralisation of response to social
      stimuli in tadpoles of five anuran species.
AB  - Tadpoles of five anuran species were tested for preferences in the use of the
      eyes during inspection of their own visual image in a mirror. When tested in a
      tank with several small mirrors, tadpoles of five different species (Bufo bufo,
      Bufo viridis, Rana temporaria, Rana esculenta, Bombina variegata) preferentially
      approached and positioned themselves with the mirror located on their left side,
      thus looking at the image with the monocular field of their left eye. Similar
      results were obtained with tadpoles of R. temporaria tested in a simple task in
      which they had to choose approaching one or other of two large mirrors located on
      their left and right side. Control experiment showed that the behavioural
      asymmetry was not due to motor preferences and that it was independent of
      morphological asymmetries in the positions of the spiracles. This is the first
      demonstration of a functional visual lateralisation among juvenile amphibia
      before metamorphosis.

PMID- 12191830
TI  - Differential effects of bicuculline and muscimol microinjections into the nucleus
      basalis magnocellularis in taste and place aversive memory formation.
AB  - The role of the nucleus basalis magnocellularis (NBM) in learning and memory has
      been demonstrated in different learning paradigms such as conditioned taste
      aversion (CTA) and inhibitory avoidance (IA). This participation has been related
      to the cholinergic system, but recent studies have reported the potential role of
      other neurotransmitters such as GABA. The effects of acute intracerebral
      administration of the GABAergic antagonist bicuculline (0.05 microg) and the
      GABAergic agonist muscimol (0.05 microg) into the NBM of male Wistar rats were
      assessed in CTA and IA learning. In both learning tasks, the drug administration
      was performed before the acquisition. Taste aversion learning was not affected by
      the infusion of any of the drugs administered. IA acquisition was not affected by
      the administration of bicuculline or muscimol, requiring similar number of trials
      to reach the learning criterion. However, when the rats were tested 24 h later,
      those injected with bicuculline or muscimol showed an impairment of the IA
      learning. The present results support a role of the GABAergic system in the
      consolidation process of IA learning.

PMID- 12191831
TI  - Effects of fimbria-fornix lesion and amyloid pathology on spatial learning and
      memory in transgenic APP+PS1 mice.
AB  - Transgenic mice carrying mutated human amyloid precursor protein (APPswe) and
      presenilin (PS1, A246E) genes develop first amyloid plaques around 9 months of
      age, but up to 18 months of age, amyloid depositions in these mice were largely
      restricted to the hippocampus, subiculum, and neocortex. To assess the behavioral
      consequences of amyloid accumulation in the hippocampal formation, we compared
      the effects of APP+PS1 (AP) genotype and fimbria-fornix (FFX) transection, either
      alone or combined, on various spatial learning and memory tasks. Both FFX
      lesioned and AP mice were impaired in spatial navigation in the water maze, a
      typical hippocampal dependent task. Conversely, neither group of mice was
      impaired in a win-stay version of the radial arm maze (RAM) or position
      discrimination in the T-maze, tasks that do not depend on the hippocampus. FFX
      lesioned mice were impaired in the win-shift version of the RAM, and in
      spontaneous and rewarded alternation in the T-maze, while AP mice performed equal
      to non-transgenic controls in all these working memory tasks, except long-term
      retention of the RAM task. AP mice thus appear to have a selective deficit in
      hippocampal dependent long-term memory, as do Alzheimer patients at early stage
      of the disease.

PMID- 12191832
TI  - Light exposure of the chick embryo influences monocular sleep.
AB  - Together with some aquatic mammals, several species of birds, such as the
      domestic fowl, exhibit a particular behavioural and electrophysiological state
      called 'unihemispheric sleep', in which one cerebral hemisphere is awake and the
      other is sleeping. Slow-wave sleep in one hemisphere is associated with closure
      of the contralateral eye, whilst the eye contralateral to the awake hemisphere is
      open; closure of both eyes, in contrast, is associated with bihemispheric slow
      wave sleep or with REM sleep. During the last few days of incubation the chick
      embryo is turned in the egg so that it occludes its left eye, whereas light
      entering through the shell can stimulate the right eye. We found that in the
      first 2 days after hatching chicks coming from eggs incubated in the light and
      reared with an imprinting object slept mostly with their right-eye open, whereas
      those coming from eggs incubated in the dark slept mostly with their left-eye
      open. In chicks reared without an imprinting object, in contrast, the effect of
      incubation extended over the first 2 weeks in females, with dark-incubated chicks
      showing more pronounced left-eye closure than light-incubated chicks, whereas the
      effect of incubation was similar to that observed in chicks reared with the
      imprinting object during the first 2 days post-hatch in males and more variable
      from day to day thereafter. Asymmetric light stimulation of embryos can thus
      modulate, though it does not generate, the left-right direction of eye opening
      during post-hatching monocular sleep; apparently, such a modulation depends on
      the emotional/motivational state of the animal associated with the outcomes of a
      naturally occurring visual imprinting.

PMID- 12191833
TI  - Place and matching-to-place spatial learning affected by rat inbreeding (Dark
      Agouti, Fischer 344) and albinism (Wistar, Sprague-Dawley) but not domestication
      (wild rat vs. Long-Evans, Fischer-Norway).
AB  - Domestication has been shown to produce a shift in both morphological and
      behavioral characteristics of animals. While changes in body weight, brain size,
      reproductive rates, and temperament are well documented, the effects of
      domestication on learning and memory are not as clearly understood. This issue is
      of particular importance to the use of rodent models in learning and memory where
      the domestication of Rattus norvegicus for research has resulted in the
      availability of numerous strains. To investigate cognitive effects resulting frm
      domestication, we examined the spatial performance of a number of rat strains:
      wild, Long-Evans, Fischer-Norway, Dark-Agouti, Wistar, Fischer 344, Sprague
      Dawley. The wild rats served as a baseline for comparing inbred and outbred
      domestic strains and pigmented and albino domestic strains. Place (a measure of
      nonspatial and procedural learning), matching-to-place (spatial working memory),
      and probe (retention) performance were measured in the Morris swimming pool task.
      The task is an ideal means for comparing different rat strains because place
      learning has not been selected for in the domestication of Rattus norvegicus and
      because the task is ethologically relevant. The results indicated that wild rats
      and Long-Evans rats did not differ on any measure, with Fischer-Norway rats being
      only slightly inferior. Larger impairments were found in Wistar > Fischer 344 >
      Dark-Agouti > Sprague-Dawley strains. Impairments were more obvious on place
      acquisition but also occurred in matching-to-place performance. Platform crosses,
      but not quadrant preference was found to be correlated with place learning. In
      general, although nonspatial and spatial deficits were associated with both
      inbreeding and albinism, impaired spatial performance is not a necessary result
      of domestication.

PMID- 12191834
TI  - Reduction of cGMP and nitric oxide has antidepressant-like effects in the forced
      swimming test in rats.
AB  - The forced swimming test (FST) has been extensively used as a screening model for
      new antidepressant agents. It has been shown that drugs which reduce the amount
      of nitric oxide (NO) have the same outcome in this model as classic
      antidepressants. In addition, previous studies have shown that methylene blue,
      which acts as a direct inhibitor of both NOS and soluble guanylate cyclase (sGC),
      mimics the effect of clinically effective antidepressants in patients and in the
      FST. The present study examined the effects of the specific inhibitor of the NO
      sGC pathway, [1H-[1,2,4]Oxadiazole[4,3-a]quinoxalin-1-one] (ODQ) and of the
      neuronal NOS inhibitor 7-nitroindazole (7-NI) in the FST. We found that ODQ (10
      and 20 mg/kg) significantly decreased the immobility time in the FST compared to
      the control. Similarly, injections of 7-NI (30 or 60 mg/kg) reduced immobility
      time as well as Imipramine (IMI, 30 mg/kg). Interestingly, L-Arginine (250 mg/kg)
      administered in combination with ODQ reversed the effect of ODQ but displayed no
      effect when administered alone. Locomotion activity was significantly decreased
      following administration of IMI (30 mg/kg) and 7-NI (30 and 60 mg/kg) but was
      unaffected after administration of ODQ (10 and 20 mg/kg). These findings suggest
      that the NO-sGC-cGMP pathway may play an important role in the mediation of the
      behavioural effect in the FST without influence on motor activity.

PMID- 12191835
TI  - Effects of salient environmental stimuli on extracellular adenosine levels in the
      rat nucleus accumbens measured by in vivo microdialysis.
AB  - In the nucleus accumbens (NAc), the neuromodulator adenosine plays a major role
      in control of behaviour. The NAc subserves behaviour governed by salient stimuli
      in the environment, however, it is unknown whether such stimuli and the
      behavioural effects elicited are associated with changes in NAc extracellular
      adenosine levels. In order to further characterise the neuromodulatory actions of
      adenosine, the present study investigated for the first time the effects of four
      prototypical stimuli known to involve NAc processing on extracellular levels of
      adenosine in the NAc. Using in vivo microdialysis, the following stimuli were
      examined: (1) an appetitive, unfamiliar stimulus (palatable food), (2) an
      appetitive, familiar stimulus (standard laboratory food), (3) an aversive
      stimulus (handling) and (4) a novelty stimulus (cage change). Results revealed
      that neither of these stimuli significantly changed extracellular adenosine
      levels in the NAc. These findings demonstrate that NAc extracellular adenosine is
      not responsive to a number of prototypical salient stimuli in the environment.
      Thus the data provide no clues to suggest that transient changes of extracellular
      adenosine in the NAc modulate behavioural responses governed by these stimuli.

PMID- 12191836
TI  - Testing the spatial- versus object-learning distinction: water-maze performance
      of male rats exposed to ethanol during the brain growth spurt.
AB  - This study investigated the effects of exposure to ethanol during the brain
      growth spurt on a visual-discrimination (VD) and a place-learning task (PL) using
      intra-maze cues in the water maze. Artificially reared male Long-Evans rats were
      exposed to ethanol (ET) in a binge pattern from postnatal days 6-9 (6.5 g kg(-1)
      x day(-1); BAC approximately 330 mg/dl) or an isocaloric maltose-dextrin solution
      (gastrostomy control). A third suckled control group was reared by lactating
      dams. In experiment 1, rats were trained to discriminate horizontal- (H) versus
      vertical-striped (V) cues, with the positive cue providing escape from water.
      Groups did not differ with V+, but ET rats made more errors with H+. In
      experiment 2, the ET group was impaired in learning the spatial location of a
      submerged platform relative to intra-maze cues. In both tasks, acquisition
      deficits among ET rats were characterized by impairment emerging at trial 2, with
      intact reference memory on trial 1, and the ET group reached a comparable level
      of performance to controls by the end of training. In summary, because impairment
      was related to task characteristics, a clear distinction between impaired spatial
      versus cue-based learning was not supported. However, these findings do support
      an effect of exposure to ethanol during the brain growth spurt on recent event,
      but not reference, memory.

PMID- 12191837
TI  - The effect of retrograde and anterograde glucose administration on memory
      performance in healthy young adults.
AB  - Memory for a list of 20 words can be enhanced by preceding learning by
      consumption of 25 g of glucose, compared with consumption of an equally sweet
      aspartame solution (Psychopharmacology 137 (1998) 259; Psychopharmacology 157
      (2001) 46). However, using this anterograde administration procedure, it is
      impossible to separate whether glucose affects encoding, consolidation, or
      retrieval. The present placebo-controlled, double-blind study investigated the
      effect of anterograde and retrograde administration on memory performance in
      healthy young participants. In order to evaluate whether post-acquisition
      administration of glucose can improve memory performance and to compare possible
      differences in the size of the effect, participants were administered 25 g of
      glucose immediately before or immediately after presentation of a word list.
      Moreover, in order to investigate whether the effect of glucose administration on
      memory performance is time-dependent, a third group received 25 g of glucose 15
      min before learning the word list. Word- list recall was tested 30 min and 24 h
      after word list presentation. Measures of spatial memory performance and working
      memory were also evaluated. The results of this study showed that both pre- and
      post-acquisition oral glucose administration (25 g) can improve memory
      performance. However, as the time interval between anterograde glucose
      administration and memory encoding increased, the glucose memory facilitation
      effect decreased. This study provides evidence that glucose enhances memory
      performance in healthy young people even when it is given after learning has
      taken place, and that this effect is observed at least up to 24 h after glucose
      administration. Moreover, it provides evidence that the effect of glucose on
      memory performance may be time-dependent, as the enhancement of retention was
      decreased when the administration-learning interval was increased.

PMID- 12191838
TI  - Neurobehavioral analysis of developmental iron deficiency in rats.
AB  - Iron deficiency (ID) in early life alters the course of behavioral and cognitive
      development in humans, causing decreased physical activity and responsiveness to
      the environment. The effects of ID on behavior are similar in rats and
      hypothesized to be related to ID-related impairments in central dopamine
      pathways. The objective of this study was to examine the association between
      brain iron measures of dopamine function, and behavioral measures of activity and
      reactivity. Male and female weanling rats were fed either an iron deficient diet
      or control diet for 6 weeks. The iron deficient rats showed significantly
      decreased activity and increased anxiety-like behaviors. Iron deficient rats also
      showed significant decrements in brain iron content in the corpus striatum,
      prefrontal cortex, and midbrain and decreases in dopamine receptors and the
      transporter in the same areas. Multiple regression analysis showed ventral
      midbrain iron concentration and dopamine D(1) receptor density to be highly
      associated with exploration and repeated movements, respectively. In addition,
      the results showed anxiety-like behaviors to be related to prefrontal cortex
      dopamine transporter and dopamine D(1) receptor densities. We conclude from these
      analyses that iron concentration in dopamine containing regions and densities of
      dopamine receptors and the transporter, are significant predictors of measures of
      activity and reactivity. These observations also strengthen the argument that the
      Fe-dopamine link is fundamental to understanding biobehavioral difficulties seen
      in children with ID anemia.

PMID- 12191839
TI  - Infrared study of human serum very-low-density and low-density lipoproteins.
      Implication of esterified lipid C=O stretching bands for characterizing
      lipoproteins.
AB  - Fourier-transform infrared (FT-IR) spectroscopy was applied to examine human
      serum very-low-density lipoprotein (VLDL) and low-density lipoprotein (LDL) in
      aqueous solution and in solid film for characterizing lipid components. On the
      basis of the FT-IR second-derivative spectra for standard samples of
      triglycerides, cholesterol esters and phospholipids, it was found that the band
      at 1746 cm(-1) for VLDL and the band at 1738 cm(-1) for LDL were mainly due to
      the unsaturated triglycerides and unsaturated cholesterol esters, respectively.
      The implications of ester C=O stretching bands are discussed.

PMID- 12191840
TI  - Synthesis of arsinolipids. II. A non-isosteric analogue of fully acylated
      cardiolipin.
AB  - 2-Hydroxypropane-1,3-bis(arsonic acid) after six successive reactions gives the
      arsinolipid 2-acyloxy-As, As'-bis[2,3-di(acyloxy)propyl]propane-1,3
      diylbis(arsinic acid) in 20-40% overall yields. This arsinolipid is a non
      isosteric analogue of the fully acylated cardiolipin. The R- and S-glycidol, used
      to create the backbone of the lipid, give the optically active RR and SS,
      respectively, arsinolipids, while the rac-glycidol produces a mixture of
      diastereomers (a racemic pair, RR and SS, and two meso forms with an RS
      configuration). Some properties of these arsinolipids are described, from which
      the most interesting are the facile hydrolysis of the middle acyl group and their
      tendency to absorb environmental water.

PMID- 12191841
TI  - Origin of membrane dipole potential: contribution of the phospholipid fatty acid
      chains.
AB  - The large intrinsic membrane dipole potential, phi(d), is important for protein
      insertion and functioning as well as for ion transport across natural and model
      membranes. However, the origin of phi(d) is controversial. From experiments
      carried out with lipid monolayers, a significant dependence on the fatty acid
      chain length is suggested, whereas in experiments with lipid bilayers, the
      contribution of additional -CH(2)-groups seems negligibly small compared with
      that of the phospholipid carbonyl groups and lipid-bound water molecules. To
      compare the impact of the -CH(2)-groups of dipalmitoylphosphatidylcholine (DPPC)
      near and far from the glycerol backbone, we have varied the structure of DPPC by
      incorporation of sulfur atoms in place of methylene groups in different positions
      of the fatty acid chain. The phi(d) of symmetric lipid bilayers containing one
      heteroatom was obtained from the charge relaxation of oppositely charged
      hydrophobic ions. We have found that the substitution for a S-atom of a -CH(2)
      group decreases phi(d). The effect (deltaphi(d) = -22.6 mV) is most pronounced
      for S-atoms near the lipid head group while a S-atom substitution in the C(13)-
      or C(14)-position of the hydrocarbon chain does not effect the bilayer dipole
      potential. Most probably deltaphi(d) does not originate from an altered dipole
      potential of the acyl chain containing an heteroatom but is mediated by the
      disruption of chain packing, leading to a decreased density of lipid dipoles in
      the membrane.

PMID- 12191842
TI  - Influence of different ceramides on the structure of in vitro model lipid systems
      of the stratum corneum lipid matrix.
AB  - Human stratum corneum (SC) consists of several layers of keratinized corneocytes
      embedded in a lipid matrix of ordered lamellar structure which is considered to
      constitute the major barrier to percutaneous penetration. Artificial mixtures of
      SC lipids are often used as model systems to mimic the skin barrier or to
      investigate the effects of substances on the phase behaviour of the models. In
      the present study a SC lipid model composed of cholesterol, fatty acids and
      ceramides was used to investigate the effect of three different commercially
      available ceramide types on the microstructure and the physicochemical behaviour
      of the lipids. Polarized light microscopy, transmission electron microscopy,
      small-angle X-ray diffraction, wide-angle X-ray diffraction and differential
      scanning calorimetry (DSC) were used for physicochemical characterization. The
      results revealed a lamellar structure for all models but showed differences with
      regard to the thermal and optical behaviour depending obviously on the
      composition of the ceramide mixtures. A model containing a mixture of Cer[AS] was
      comparable to human SC lipids.

PMID- 12191843
TI  - Unusual fatty acid composition of cerebrosides from the filamentous soil fungus
      Mortierella alpina.
AB  - The cerebrosides produced by the soil filamentous fungus Mortierella alpina
      strain KG-1/95 account for about 13% of the total polar lipids extractable from
      lyophilised cells with chloroform/methanol mixtures. By means of 1H NMR and (13)C
      NMR spectroscopy, matrix-assisted laser-desorption ionisation mass spectrometry,
      and chemical degradation experiment, they have been shown to be 1-O-beta-D
      glucopyranosyl-2-N-(2'-D-hydroxyalkanoyl)-9-methylsphinga-4(E),8(E)-dienines, the
      fatty acid composition of which is unusual and consists of 2-hydroxytridecanoic
      (4%), 2-hydroxytetradecanoic (60%), 2-hydroxypentadecanoic (20%), and 2
      hydroxyhexadecanoic (16%) acids.

PMID- 12191844
TI  - Preparation of pseudo-arsonolipids: 2-acyloxypropane-1,3-bis(arsonic acids). The
      crystal structure of 2-hydroxypropane-1,3-bis(arsonic acid).
AB  - Epihalohydrins react with alkaline arsenite to give in very good yields 2
      hydroxypropane-1,3-bis(arsonic acid) (7), a key compound for the synthesis of
      pseudo-arsonolipids and more complex arsinolipids. Through a series of reduction
      to -As(SPh)(2), acylation, and oxidation to -AsO(3)H(2), pseudo-arsonolipids,
      i.e. 2-acyloxypropane-1,3-bis(arsonic acids), were obtained. These pseudo-lipids
      are very sensitive to bases, being de-acylated. The bis(arsonic acid) (7)
      crystallizes in the orthorombic space group P2(1)2(1)2(1) with unit cell
      constants a=6.911(3), b=17.496(8), c=7.002(3) A. Both arsenic atoms are
      essentially tetrahedral being bound to three oxygens and one carbon. All hydrogen
      atoms have been located. There is no intramolecular but only intermolecular
      hydrogen bonding involving all the As=O, As-OH, and C-OH groups. The C-OH group
      acts as a hydrogen donor to an acidic As-OH, and this As-OH, in turn, acts as a
      hydrogen donor to an As=O group.

PMID- 12191845
TI  - Influence of the lipid composition on the organization of skin lipid model
      mixtures: an infrared spectroscopy investigation.
AB  - The polymorphism of the lipids of the stratum corneum (SC), the top layer of the
      epidermis, has a fundamental impact on the permeability properties of the skin
      barrier. In this work, we have examined by infrared spectroscopy the thermal
      behavior of model mixtures involving ceramide, palmitic acid and cholesterol, the
      three main components of the SC lipids, to gain a refined description of the
      participation of the various lipid species in the different phases observed as a
      function of temperature. The results show that below 40 degrees C ceramide,
      cholesterol and palmitic acid exist mainly in crystalline domains and the lipidic
      species show very limited miscibility. Between 40 and 50 degrees C, a transition
      from the crystalline to a liquid ordered (lo) phase occurs and it involves
      ceramides, cholesterol and palmitic acid. When the mixture has a high cholesterol
      content, this lo phase is stable up to 75 degrees C. For low cholesterol content,
      the mixtures undergo a second transition toward a more disordered phase which is
      likely not lamellar. The formation of these phases is critically dependent on the
      lipid composition and, therefore, it is likely that composition changes of SC
      lipids affect the phase behavior and, consequently, the skin barrier properties.

PMID- 12191846
TI  - The effect of protein stability on protein-monoglyceride interactions.
AB  - We have previously shown that proteins such as beta-lactoglobulin and lysozyme
      insert into monoglyceride monolayers and are able to induce an L(beta) to coagel
      phase transition in monoglyceride bilayers. These studies gave a first indication
      that protein stability could be an important factor for these interactions. This
      study therefore aims at further investigating the potential role of protein
      stability on protein-monoglyceride interactions. To this end we studied the
      interaction of stable and destabilized alpha-lactalbumin with
      monostearoylglycerol. Our results show that protein stability is important for
      the insertion of proteins into a monostearoylglycerol monolayer, such that the
      lower the stability of the protein the better the protein inserts. In marked
      contrast to beta-lactoglobulin and lysozyme we found that destabilized alpha
      lactalbumin does not induce the L(beta) to coagel phase transition in
      monoglyceride bilayers. We propose that this is due to an increased surface
      coverage by the protein which could result from the unfolding of the protein upon
      binding to the interface.

PMID- 12191847
TI  - Results from WHI and HERS II--implications for women and the prescriber of HRT.

PMID- 12191848
TI  - National differences in lipid response to postmenopausal hormone replacement
      therapy.
AB  - OBJECTIVE: To compare the response of serum lipids and lipoproteins to the
      transdermal hormone replacement therapy (HRT) in five European countries.
      METHODS: Five-hundred and sixty-seven healthy postmenopausal women from Belgium,
      Finland, the Netherlands, Sweden, and the UK received transdermal estradiol 50
      microg daily for 12 months. In addition, two groups received transdermally
      norethisterone acetate (NETA) continuously, two groups sequentially (170 or 350
      microg/day); one group received sequentially oral NETA (1 mg/day), and one group
      dydrogestrone (20 mg/day). Serum total cholesterol, HDL-, HDL2-, LDL-cholesterol,
      lipoprotein(a) (Lp(a)), and triglycerides were assessed before and at the end of
      treatment. RESULTS: No significant national differences existed in the
      pretreatment levels of lipids and lipoproteins. Mean cholesterol, LDL, Lp(a), and
      triglycerides decreased during HRT, and HDL and HDL2 increased. Individual
      changes in responses to HRT were strongly dependent on pretreatment values. In
      this regard, British women differed from the others: their cholesterol, HDL,
      HDL2, and Lp(a) responses, when related to the pretreatment levels, were smaller
      than those of the others. CONCLUSION: A national difference discovered in
      response of serum lipids to HRT calls for caution in generalization of lipid data
      from one nation to another during HRT.

PMID- 12191849
TI  - Assessment of the QoL in Italian menopausal women: comparison between HRT users
      and non-users.
AB  - OBJECTIVES: The aim of this cross-sectional study was to describe QoL in a large
      sample of women attending menopause centres and compare untreated postmenopausal
      women and matched HRT users by employing the Women's Health Questionnaire (WHQ)
      and two generic instruments, the SF-36 and the EQ-5D. METHODS: Overall, 2906
      women were recruited by 64 menopause centres throughout Italy, of whom 2160
      filled in the questionnaire (1093 on HRT and 1067 not on HRT; response rate:
      74%). RESULTS: HRT users tended to be younger, healthier and with shorter
      menopause duration as opposed to non users, while no major socio-economic
      differences were present. At multivariate analysis, the presence of chronic
      diseases, low socio-economic status and living in Southern Italy represented the
      most important predictors of poor QoL. Furthermore, HRT users showed a lower
      probability of reporting problems in usual activities and pain/discomfort (EQ
      5D), role limitations due to emotional problems (SF-36) and anxiety/fears (WHQ).
      HRT users also showed highly significant better outcomes in those areas that are
      more directly attributable to hormonal changes of mid age, namely vasomotor
      symptoms and sexual problems. CONCLUSIONS: Although QoL is mainly influenced by
      socio-economic and cultural factors, HRT has the potential for improving not only
      symptoms, but also more general aspects of physical and psychological well-being
      of symptomatic postmenopausal women.

PMID- 12191850
TI  - The values of urinary NTx in postmenopausal women undergoing HRT; the role of
      additional alendronate therapy.
AB  - OBJECTIVE: To determine the changes in levels of urinary NTx at the end of the
      6th month of oral and transdermal hormone replacement therapy (HRT) and the
      effects of additional alendronate therapy for osteoporotic women. METHOD: Of 66
      postmenopausal women 23 were treated with oral estradiol+norethisterone acetate
      (E+P), and 22 were treated with transdermal estradiol+norethisterone acetate. The
      third group consisted of 21 women with osteoporosis (bone mineral density < 100
      mg/cm(3)) and treated with oral E+P plus alendronate 10 mg/day. RESULT:
      Significant decreases of urinary NTx levels were seen after HRT in all study
      groups (P < 0.05). But the decline of NTx levels was not different between the
      oral and transdermal HRT groups (P > 0.05). There was no additional decrease in
      the levels of NTx with alendronate therapy (P > 0.05) but NTx excretion
      diminished more in patients with high baseline levels. CONCLUSION: The decline of
      NTx at the end of the 6th month of HRT reflects the decrease of bone resorption
      and it is not related to the route of administration.

PMID- 12191851
TI  - Lack of stimulatory effect of dienogest on the expression of intercellular
      adhesion molecule-1 and vascular cell adhesion molecule-1 by endothelial cell as
      compared with other synthetic progestins.
AB  - OBJECTIVES: Monocyte adhesion to endothelial cells is an important initial event
      at the onset of atherosclerosis. It is partially mediated by the expression of
      adhesion molecules on the endothelial cell surface. While estrogens inhibit the
      development of atherosclerosis, the effect of co-administered progestin remains
      controversial. We examined the effect of progestins on cytokine-stimulated human
      umbilical venous endothelial cell (HUVEC) expression of adhesion molecules.
      METHODS: In HUVECs, mRNA expression of progesterone receptors (PRs) and androgen
      receptors (AR) was determined by RT-PCR. HUVECs were stimulated by interleukin
      1beta (IL-1beta) for 24 h with or without various steroids, and then the cell
      surface expression of intercellular adhesion molecule-1 (ICAM-1) and vascular
      cell adhesion molecule-1 (VCAM-1) was semiquantified by ELISA. RESULTS: In all
      preparations of HUVECs used in this study, RT-PCR confirmed mRNA expression of
      both isoforms of PR, PR-A and PR-B, as well as AR. Addition of progesterone (10(
      10)-10(-7) M) or dienogest (DNG) (10(-10)-10(-8) M) did not affect IL-1beta
      stimulated ICAM-1 or VCAM-1 expression. In contrast, medroxyprogesterone acetate,
      norethindrone acetate and levonorgestrel (10(-10)-10(-8) M) dose-dependently
      increased cell adhesion molecules. The progestin-induced increase was blocked by
      the concomitant addition of mifepristone, a PR antagonist, but not by
      hydroxyflutamide, an AR antagonist, indicating that the progestin stimulation was
      mediated predominantly via PR. CONCLUSIONS: These results suggest that DNG,
      unlike other synthetic progestins, lacks stimulation of cell adhesion molecules.
      For the prevention of atherosclerosis, estrogen in combination with DNG may be a
      suitable regimen in hormone replacement therapy in postmenopausal women.

PMID- 12191852
TI  - Efficacy of a soy rich diet in preventing postmenopausal osteoporosis: the Menfis
      randomized trial.
AB  - OBJECTIVES: To compare the effect of a soy rich diet and hormone replacement
      therapy (HRT) on the main biomarkers of bone turnover and bone mineral density
      (BMD) at postmenopausal age. METHODS: 187 healthy asymptomatic postmenopausal
      women, aged 39-60, were recruited and randomized into a soy rich diet group, a
      HRT group, and a control group. Bone biomarkers and BMD were evaluated at
      baseline and after 6 months at the end of the study. RESULTS: Diet is not as
      effective as HRT in reducing the postmenopausal turnover; however diet stimulates
      bone osteoblastic activity, as evidenced by significant increase in osteocalcin
      concentrations. BMD decreases significantly only in the control group, but not in
      the intervention groups. CONCLUSIONS: Our data suggest that soy products could be
      effective in reducing the risk of osteoporosis in asymptomatic postmenopausal
      women, but our findings should be confirmed before recommending the diet as a
      valid alternative to HRT.

PMID- 12191853
TI  - Relative contribution of aging and menopause to changes in lean and fat mass in
      segmental regions.
AB  - OBJECTIVE: The aim of the study was to investigate the relative contribution of
      aging and menopause to the changes in lean and fat mass in segmental regions.
      MATERIALS AND METHODS: Subjects were 365 pre- and 201 postmenopausal Japanese
      women aged between 20 and 70 years old. Age, height, weight, body mass index
      (BMI, Wt/Ht(2)), age at menopause, years since menopause (YSM), and menopausal
      status were recorded. Lean and fat mass of the arms, trunk, legs, total body, and
      the ratio of trunk fat mass to leg fat mass amount (trunk-leg fat ratio) were
      measured by dual-energy X-ray absorptiometry (DEXA). Regional (arms, lumbar
      spine, pelvis, legs, and total body) bone mineral density (BMD) were measured by
      DEXA. RESULTS: Total body lean mass and regional BMD decreased (P < 0.001), while
      percentage of body fat, trunk fat mass, and trunk-leg fat ratio increased (P <
      0.001) with aging and after menopause. On multiple regression analyses, trunk and
      total body lean mass were inversely correlated with menopausal status (P < 0.001
      and 0.05, respectively) but not with age. Trunk fat mass, trunk-leg fat ratio,
      and percentage of body fat were positively correlated with age (P < 0.01) but not
      with menopausal status. Regional BMD were more inversely correlated with
      menopausal status (P < 0.001) than age. CONCLUSION: Decrease in lean mass and BMD
      are more menopause-related, while the shift toward upper body fat distribution
      and overall adiposity are more age-related. Lean tissue is similar to bone tissue
      from the viewpoint of more undergoing menopausal effect.

PMID- 12191855
TI  - Zero exposure--a goal for environmental and occupational health?
AB  - Humans live on chemicals, and no exposure to any chemicals is incompatible with
      life. Chemicals produced by different organisms are in no basic way different
      from the man-made chemicals, and often chemicals are produced by both. Natural
      chemicals include the most potent acutely toxic chemicals known, and also include
      very potent mutagens and human carcinogens. Thus the fact that a chemical is
      'natural' does not mean that it is any safer than a man-made chemical, and the
      fact that a chemical is man-made does not make it any more harmful than 'natural'
      chemicals. Exposure to chemicals varies widely, to a large variety of chemicals
      people are exposed from the environment, via drinking water, food and inhaled air
      and exposure e.g. at the work-place is only quantitatively different from the
      exposure of the general public. Zero exposure is meaningless without an
      operational definition. It is a major challenge to the society to determine what
      is the safe exposure level to different chemicals, and for chemicals for which no
      exposure level is safe, to define the acceptable risk, and in both cases, make
      sure that the exposure limits thus determined are complied with.

PMID- 12191856
TI  - Biological monitoring of exposure to mixtures.
AB  - This short review is aimed at establishing general principles of biological
      monitoring for chemical mixtures. When interactions occur, they appear to be
      toxicokinetic in nature, often resulting from competition between two or more
      substances for the same biotransformation enzymes. A threshold is frequently
      observed for such an interaction, so that it might not influence the relationship
      between the absorbed dose and the value of the relevant biomarker. The extent of
      the interaction between pairs of chemicals also depends on the extent of
      biotransformation of each compound. As a result, the measurement of the parent
      compound or its metabolite will be differentially influenced by the presence of
      an interfering chemical. Biological limit values (BLV) are often established from
      the correlation between the bioindicator concentration in a given biological
      medium and the airborne concentration of the parent compound. When this
      relationship is derived from exposure to pure chemicals, it might not always
      yield an appropriate BLV for monitoring exposure to a mixture that includes this
      particular chemical. Under certain conditions such as the stability of mixture
      composition, a single biomarker such as 1-hydroxypyrene in PAH exposure can be
      used to reflect the overall exposure to a mixture. Finally, there is clearly a
      need for a greater research effort on the toxicology of mixtures to make
      biological monitoring a useful tool in occupational health.

PMID- 12191857
TI  - Biomarkers for male reproductive health hazards: are they available?
AB  - This review aims to give an overview of some of the biomarkers that have been
      used for the monitoring of human exposure to xenobiotics as well as to provide a
      summary of some of the recent epidemiological studies on male reproductive health
      of exposure to environmental and occupational toxicants. Possible molecular
      mechanisms on seminal quality change are also suggested. Studies using various
      biomarkers have no doubt enabled us to better characterize the effect of
      environmental pollutants on the male reproductive system. However, the
      sensitivity and specificity of these biomarkers have not been comprehensively
      validated. Furthermore, many epidemiological findings are difficult to replicate
      owing to the inherited methodological problems of male reproductive health
      investigations, such as the small number of study subjects, low compliance rate,
      substantial intra-individual variability in semen parameters, measurement
      techniques and misclassifications based on single assay. Oxidative damage, in
      particular DNA-damage caused by free radicals, generated either by xenobiotics,
      or endogenously, is now thought to be a key molecular mechanism associated with
      semen quality and sperm function. Laboratory studies and epidemiological findings
      have suggested that the male reproductive system is susceptible to reactive
      oxygen species (ROS). On the other hand, there is so far no single all
      encompassing biomarker of reproductive capacity in men. A panel of biomarkers
      with specific goals should be considered. Collaborative multidisciplinary studies
      are also needed to overcome some of the issues mentioned here.

PMID- 12191858
TI  - Mouse models for generating P53 gene mutation spectra.
AB  - The p53 tumor suppressor gene lends itself to mutation spectra analysis, because
      the frequency of point mutations in human tumors is high, the locations of
      inactivating tumor mutations are numerous and dispersed, and all possible base
      substitutions are observed in human cancer. P53 tumor mutations induced
      experimentally in mice exposed to carcinogens have been described, but have not
      yet contributed significantly to our understanding of mutagenic mechanisms or of
      the origins of mutations in human cancers. Recently, gene-targeting technology
      has allowed development of a new mouse model, which explores experimentally the
      endogenous and environmental factors that may contribute to neoplastic disease in
      humans.

PMID- 12191859
TI  - Carcinogen biomonitoring in human exposures and laboratory research: validation
      and application to human occupational exposures.
AB  - A multiple biomarker approach is required to integrate for metabolism, temporal
      response and exposure-response kinetics, biological relevance, and positive
      predictive value. Carcinogen DNA adduct analysis can be used in animal and in
      vitro studies to detect absorption permutations caused by mixture interactions,
      and to control metabolic variation when specific CYP450 genes (1A1 or 1A2) are
      knocked out. These enzymes are not critical to the metabolic activation of model
      Polycyclic Aromatic Compounds (PAC) and aromatic amines, respectively, as
      suggested by in vitro analysis. Several human studies have been carried out where
      multiple biomarkers have been measured. In a study of benzidine workers, the
      similarities in elimination kinetics between urinary metabolites and mutagenicity
      is likely responsible for a better correlation between these markers than to BZ
      DNA adducts in exfoliated cells. In a study of rubber workers, the relationship
      between specific departments, urinary 1 HP and DNA adducts in exfoliated cells
      coincided with the historical urinary bladder cancer risk in these departments;
      the same relationship did not hold for urinary mutagenicity. In a study of
      automotive mechanics, biomarkers were used to monitor the effectiveness of
      exposure interventions. These data reinforce the notion that carcinogen
      biomarkers are useful to monitor exposure, but that a complementary approaches
      involving effect and perhaps susceptibility biomarkers is necessary to obtain the
      necessary information.

PMID- 12191860
TI  - The enemy at the gates? DNA adducts as biomarkers of exposure to exogenous and
      endogenous genotoxic agents.
AB  - Genomic DNA is under continuous assault by various chemical species produced by
      normal cellular metabolism. In addition, exposure to exogenous agents adds
      further insult. Modification of DNA by chemical carcinogens has long been
      recognized as an early event in carcinogenesis and many DNA adducts have been
      characterized. There appears to be great value in using DNA adducts as markers of
      exposure to genotoxic (i.e. DNA-damaging) agents and some may be even more useful
      as indicators of risk of disease. Studies of the relationship between aflatoxin
      exposure and liver cancer have illustrated particularly well the advantages of
      using specific DNA adducts and other biomarkers, not only to better
      characteristic the risk factors, but also as endpoints in intervention studies.
      DNA adducts of endogenous genotoxins such as malondialdehyde and nitrosated
      glycine are particularly informative in studies of the effects of diet on cancer
      risk. DNA adducts may also be useful in identifying no-exposure levels in risk
      assessment of low-level environmental exposures such as 1,3-butadiene (BD).

PMID- 12191861
TI  - Biological monitoring of hospital personnel occupationally exposed to
      antineoplastic agents.
AB  - To detect trace amounts of urinary cyclophosphamide (CP), ifosfamide (IF) and
      methotrexate (MTX), sensitive and specific high-performance liquid
      chromatography/ tandem mass spectrometry (HPLC-MS/MS) procedures, incorporating
      either liquid-liquid (for CP and IF), or solid-phase, extraction (for MTX) have
      been developed. Urinary platinum (Pt) was also detected using inductively coupled
      plasma-mass spectrometry (ICP-MS). These methods showed acceptable imprecision
      and inaccuracy. The limit of detection (LOD) was 50 ng/l for CP and IF, 200 ng/l
      for MTX and 1 ng/l for Pt. Biomonitoring was performed on two consecutive days on
      nine subjects preparing, and seven administering, antineoplastic drugs. Urine was
      collected at the beginning, at the end and during the work shift. Eighteen urine
      samples were positive for CP (range: 50-10031 ng/l), whereas IF was detected in
      one subject only (153 ng/l). LOD was never exceeded for MTX. In urine samples
      from nurses and pharmacy technicians, Pt was detected in three subjects (range
      920-1300 ng/l). These findings were compared with the results from a previous
      survey carried out in the same hospital when different work practices were in
      use. The proposed methods are simple, fast and reliable and can be used to
      identify exposure of hospital personnel handling antineoplastic drugs.

PMID- 12191862
TI  - Hemoglobin adducts of ethylene oxide, propylene oxide, acrylonitrile and
      acrylamide-biomarkers in occupational and environmental medicine.
AB  - In a chemical plant, ethylene oxide (EO) and propylene oxide (PO) were used for
      the production of surfactants for the textile industry. Within health
      supervision, we investigated the internal exposure of the workers using
      hemoglobin adducts as parameters of biochemical effects. The 95th percentile for
      N-2-hydroxyethylvaline (HEV) was 1280 pmol/g globin (=29.4 microg/l blood) in
      blood from exposed workers compared with 100 pmol/g globin (or 2.3 microg/l) in
      controls. N-(R,S)-2-hydroxypropylvaline (HPV) both in workers and controls was
      below the detection limit (80 pmol/g globin or 2 microg/l). The levels of the
      adducts of acrylonitrile (ACN) and acrylamide (AA) were also determined, though
      they were mainly accounted for by smoking and diet. Median values of N-2
      cyanoethylvaline (CEV) were below 4 pmol/g globin (or 0.1 microg/l) in non
      smokers (n=24) and 131 pmol/g globin (or 3.3 microg/l) in smokers (n=38). Median
      values of N-2-carbamoylethylvaline (AAV) were 22 pmol/g globin (or 0.6 microg/l)
      in non-smokers compared with 89 pmol/g globin (or 2.4 microg/l) in smokers.
      Correlations were found between smoking habits and adduct levels of CEV and AAV.

PMID- 12191863
TI  - Analysis of ethenoguanine adducts in human urine using high performance liquid
      chromatography-tandem mass spectrometry.
AB  - Several chemical carcinogens, such as vinyl chloride and ethyl carbamate, can
      react with DNA to form etheno-adducts in vitro and in vivo, which can be repaired
      through the base excision repair pathway, and then excreted with the urine. A
      specific and sensitive method, based on high performance liquid chromatography
      electrospray ionization tandem mass spectrometry, was developed for the detection
      of ethenoguanines (1,N2-ethenoguanine and its isomer N2,3 ethenoguanine) in
      urine. Urine samples were obtained from 13 healthy subjects not occupationally
      exposed to industrial chemicals. A confirmatory GC/MS method was also applied.
      Ethenoguanine isomers excreted with the urine were in the low nmol/l range (<0.3
      8 nmol/l). Since occupational exposure to chemicals that may form etheno-adducts
      can be ruled out, endogenously produced intermediates, such as 2,3-epoxy-4
      hydroxynonanal, may be responsible for the formation of etheno-adducts in human
      DNA. The background level of the general population has to be taken into account,
      especially in the investigation of persons occupationally exposed to etheno
      adduct forming chemicals.

PMID- 12191864
TI  - Chromosomal aberrations in peripheral lymphocytes of children as biomarkers of
      environmental exposure and life style.
AB  - The original purpose of our study was to determine if the detection of
      chromosomal aberrations in peripheral lymphocytes of children might be used as a
      biomarker of environmental pollution and life style. We compared the results of
      cytogenetic analyses performed in children and adolescents in the periods 1984
      1993 and 1994-1999, in a total of 3402 subjects. The frequency of aberrant cells
      (AB.C.) markedly decreased in the period 1994-1999 compared with the period 1984
      1993. The decreases in AB.C. were significant in the age groups 7-15 and 16-19
      years: 1.63% AB.C. versus 1.14% AB.C. and 2.02% AB.C. versus 1.08% AB.C.,
      respectively (P<0.01). No difference in the frequency of AB.C. was observed in
      newborns. Based on our experience, we believe that monitoring the spontaneous
      level of chromosomal aberrations in children over 5 year periods may be used to
      examine the general changes in environmental pollution in larger geographic
      areas.

PMID- 12191865
TI  - Single strand DNA breaks in T- and B-lymphocytes and granulocytes in workers
      exposed to benzene.
AB  - Comet assays were carried out to evaluate DNA damage in T- and B-lymphocytes and
      granulocytes from 41 workers exposed to benzene in a printing company and 41
      unexposed donors. In T-lymphocytes, DNA damage was slightly higher in exposed
      workers than in controls. The tail moments in the two groups were 1.75+/-0.29 and
      1.47+/-0.41, respectively (P<0.0006). DNA damage of B-lymphocytes in the two
      groups showed the most significant difference among the three cell types. The
      tail moments were 3.86+/-0.71 and 1.51+/-0.39, respectively (P<0.0001). In
      granulocytes, DNA damage was also different, the tail moments being 3.61+/-0.75
      and 2.60+/-0.59, respectively (P<0.0001). The comparison of DNA damage in both
      groups shows that B-lymphocytes could be a useful target in biomonitoring of
      human exposure to low levels of benzene.

PMID- 12191866
TI  - Biological monitoring of exposure to organophosphate pesticides.
AB  - Organophosphates (OPs) are readily absorbed through the skin and biological
      monitoring is an essential component of any comprehensive assessment of exposure.
      This paper presents a summary of our experience in a wide range of occupational
      studies. Additionally, we have conducted studies of non-occupational exposure and
      human volunteer studies looking at the kinetics of chlorpyrifos, propetamphos,
      diazinon and malathion. In non-occupationally exposed people, 95% of urinary
      alkyl phosphates do not exceed 72 micromol/mol creatinine. In occupationally
      exposed people, the corresponding 95th percentile of total urinary alkyl
      phosphates is 122 micromol/mol creatinine. In volunteer studies with 1 mg oral
      doses of chlorpyifos, diazinon and propetamphos the mean peak values were 160,
      750 and 404 micromol/mol creatinine, respectively, and were not associated with
      any reduction in blood cholinesterase activity. The levels of OP metabolites seen
      in urine from workers potentially exposed to OPs are generally low and unlikely
      to cause significant reduction in blood cholinesterase activity.

PMID- 12191868
TI  - Oral and dermal exposure to propetamphos: a human volunteer study.
AB  - Propetamphos ((E)-O-2-isopropylcarbonyl-1-methylvinyl-O-methylethyl
      phosphoramidothioate) is an organophosphate pesticide (OP) and has been used as
      an active ingredient in sheep dip where there is the potential for significant
      dermal exposure during dipping. Biological monitoring of exposure to propetamphos
      has until recently relied on the measurement of cholinesterase activity in
      plasma. Following the development of a novel method for the determination of
      propetamphos metabolites in urine, it is now possible to biologically monitor
      exposure using urine samples. This paper describes a human volunteer study
      involving oral and dermal exposure to propetamphos.

PMID- 12191867
TI  - Exposure to the organophosphate diazinon: data from a human volunteer study with
      oral and dermal doses.
AB  - Biological monitoring of occupational exposure to diazinon is possible by the
      determination of blood cholinesterase activity and by the measurement of
      metabolites in urine. However, there is little data to aid in the interpretation
      of results. This study gave oral (11 microg kg(-1) (36 nmol kg(-1)) body weight)
      and occluded dermal (100 mg (329 micromol)) doses of diazinon to five volunteers
      and analysed blood and urine samples for plasma and erythrocyte cholinesterase
      and urinary dialkyl phosphate (DAP) metabolites of diazinon: diethyl phosphate
      (DEP) and diethyl thiophosphate (DETP). Following oral and dermal exposure, peak
      urinary DAP levels occurred at 2 and 12 h, respectively. The apparent urinary
      elimination half-lives of DAP metabolites following oral and dermal exposure were
      approximately 2 and 9 h, respectively. Approximately 60% of the oral dose and 1%
      of the dermal dose was excreted as urinary DAP metabolites, with 90% of the
      dermal dose being recovered from the skin surface. On a group basis, there was no
      statistically significant mean depression in plasma or erythrocyte cholinesterase
      when compared with pre-exposure levels for either dosing experiment. The observed
      elimination kinetics of diazinon metabolites suggest a biological monitoring
      strategy for occupational exposure to diazinon based on urine samples collected
      at the end of shift.

PMID- 12191869
TI  - Biological monitoring of combined exposure to organophosphates and pyrethroids.
AB  - A total of 132 farmers were selected from two areas (J and S) for this study. In
      area J, the subgroups Ja (40 subjects) and Jb (36 subjects) sprayed on rice crops
      either the organophosphate (OP) insecticide methamidophos or the mixture
      methamidophos-deltamethrin (a pyrethroid, Pyr). In area S, the subgroups Sa (27
      subjects) and Sb (29 subjects) sprayed on cottons either the OP methyl-parathion
      or the mixture methyl-parathion-deltamethrin. Groups Jc (22 subjects) and Sc (20
      subjects) were non-exposed controls. Erythrocyte acetylcholinesterase (AChE) was
      measured by the Ellman's method before spraying, after 2-h exposure and 1 h
      later. Inhibition of AChE occurred after 2-h exposure to both single OP (Ja and
      Sa) and OP-containing mixtures (Jb and Sb) as compared with both pre-exposure and
      control values (Jc and Sc). A similar recovery was found in subgroups Ja, Jb, Sa
      and Sb 1 h after spraying, but all remained lower than the pre-exposure level.
      There was no difference in AChE inhibition and recovery between the single OP
      subgroups and the OP mixture subgroups. The inhibitory effect on AChE shown in
      subjects with combined OP-Pyr exposure was induced by the OP component of the
      insecticide mixture and to a similar extent as that induced by the single OP
      formulations. In addition to the fact that the OP is more potent than Pyrs, the
      above results might explain why the clinical manifestations of OP mixture
      poisonings are similar to those of single OP poisoning.

PMID- 12191870
TI  - Monitoring of pesticide applicators for potential dermal exposure to malathion
      and biomarkers in urine.
AB  - Malathion was applied to roses in three Finnish greenhouses by hand held lance
      sprayers. The potential dermal exposure of applicators to this insecticide was
      measured. Total urine production of each applicator was also collected up to 24 h
      post application. In the urine samples the specific metabolite of malathion,
      malathion monocarboxylic acid (MMA), and the creatinine content were determined.
      The potential dermal exposure results show that during the application of
      malathion, the applicators' lower limbs accounted, on average, for 48%, while the
      upper limbs accounted for 19% of the potential dermal exposure. Moreover, hands
      and chest and back and head regions accounted for 30 and 3%, respectively. Based
      on the urine measurements, it was observed that the excretion of MMA was very
      rapid reaching a maximum at about 6-7 h after the completion of the application.
      In the urine samples collected, MMA was found to be present in relatively small
      amounts.

PMID- 12191871
TI  - Ethylenethiourea in urine as an indicator of exposure to mancozeb in vineyard
      workers.
AB  - In the present study, the personal exposure to mancozeb and/or ethilenethiourea
      (ETU) in 13 Italian vineyard workers and in 13 subjects without occupational
      exposure to pesticides was investigated. With this aim, the level of ETU in urine
      and the dermal exposure to mancozeb were determined. Baseline urinary ETU results
      were lower than the analytical limit of detection for all controls (<0.5 microg/g
      creatinine) and for ten workers (median <0.5, range <0.5-3.4 microg/g
      creatinine). In workers, urinary ETU was significantly increased at the end of
      shift (2.5, <0.5-95.2 microg/g creatinine) compared with baseline levels. End
      shift urinary ETU was higher in operators using open tractors (n=7) than in those
      using closed tractors (n=5) (16.2 vs. 2.4 microg/g creatinine), but the
      difference was not significant (P=0.073). End-shift urinary ETU was positively
      correlated with dermal exposure to mancozeb determined both over the clothes and
      on the skin (Spearman's rho=0.770 and 0.702, P=0.009 and 0.024, respectively).
      Wine consumption positively influenced the excretion of ETU.

PMID- 12191872
TI  - Pyrethroid exposure of the general population-is this due to diet.
AB  - Inhabitants (1177) of a residential area in Frankfurt/Main have been investigated
      with respect to internal exposure to pyrethroids. Biological monitoring revealed
      a body burden of pyrethroids. The 95th per thousand for the urinary metabolites
      of pyrethroids, such as permethrin and cypermethrin, cis and trans-3-(2,2
      dichlorovinyl)-2,2-dimethylcyclopropane-1-carboxylic acid (cis-DCCA and trans
      DCCA), was determined to be 0.5 and 1.4 microg/l, respectively. 95th per thousand
      for cis-3-(2,2-dibromovinyl)-2,2-dimethylcyclopropane-1-carboxylic acid (DBCA), a
      specific metabolite of deltamethrin, and 4-fluoro-3-phenoxybenzoic acid (F-PBA),
      a metabolite of cyfluthrin, were 0.3 and 0.27 microg/l, respectively. The
      metabolic pattern found for these samples points out that pyrethroids are
      probably ingested orally with daily diet.

PMID- 12191873
TI  - Effects of DDT on paracetamol half-life in highly exposed mothers in Zimbabwe.
AB  - After assessment of the levels of DDT residues in the milk samples, 1 g
      paracetamol was administered p.o. to 28 breastfeeding mothers selected from a
      population of 116, according to DDT residues in their milk (the 14 with the
      highest values and the 14 least exposed). Post dose blood samples were taken from
      the basilic veins of the mothers at time intervals up to 4 h, post dose. The
      paracetamol blood concentrations were determined. A significantly shorter
      paracetamol half-life was found in mothers with higher DDT body burden, who also
      exhibited lower paracetamol concentrations in blood. The results highlighted
      concern for the highly exposed mothers taking paracetamol (NSAID) as an
      analgesic, or as an antipyretic.

PMID- 12191874
TI  - Impact of human variability on the biological monitoring of exposure to toluene:
      I. Physiologically based toxicokinetic modelling.
AB  - Using an approach involving physiologically based toxicokinetic (PBTK) modelling
      and Monte Carlo simulation (MCS), we investigated the impact of the biological
      variability affecting the parameters (e.g. physiological, physicochemical,
      biochemical) which determine toluene (TOL) kinetics on two exposure indicators
      (EIs): urinary excretion of o-cresol (o-CR), measured at the end of an 8 h
      exposure at 50 ppm, and unchanged TOL in blood (B-TOL) sampled prior to the last
      shift of a 5 day workweek. Population variance was described by assuming normal,
      or lognormal, distribution of parameter values and assigning to each one+/-2 S.D.
      (or+/-2 G.S.D.). PBTK-MCS (n=1000) resulted in a geometric mean (G.M.) of 0.635
      mmol/mol creatinine for urinary o-CR, upper and lower limits (95%) ranging from
      0.23 to 1.75, whereas, the GM for B-TOL was 120.6 microg/l (95% limits: 64.5
      225.7). Overall, the results showed that this approach facilitates the prediction
      of the range of BEI values that could be anticipated to occur in a group of
      workers exposed to a chemical.

PMID- 12191875
TI  - Impact of human variability on the biological monitoring of exposure to toluene,
      phenol, lead, and mercury: II. Compartmental based toxicokinetic modelling.
AB  - In order to quantify the effect of human variability on a wide range of
      biological exposure indicators (EIs), a general compartmental model was developed
      and tested on several chemicals. The model consists of four compartments. In a
      first step, it was applied to four chemicals: toluene (TOL), phenol (Ph), lead
      (Pb), and mercury (Hg). Individuals were to be exposed 8 h a day, 5 days a week.
      Physiological parameter values were set to consider a physical workload of 50 W
      12 h/day and at rest for the remaining 12 h. Monte Carlo simulations were carried
      out using realistic distributions of physiological and metabolic parameters. The
      variability extent index (VEI) and the main parameters of influence were
      determined for each of the EIs. The results were in agreement with literature
      data. The present compartmental model provides a fair description of the
      toxicokinetic (TK) variability of very different chemicals. It will, therefore,
      further be applied to investigate the variability of a wide range of biological
      indicators.

PMID- 12191876
TI  - Relationships between trace element concentrations in human blood and serum.
AB  - Trace element interactions can affect the absorption, metabolism, or effects of
      elements. Also, different elements may derive from the same source. Associations
      in biological media between element concentrations may indicate such phenomena. A
      large number of correlations were found between 13 trace elements (Co, Cu, Zn,
      Se, Rb, Rh, Pd, Cd, W, Pt, Hg, Tl, and Pb) in human blood and/or serum, as
      investigated in 372 Swedish adolescents. Notably, serum Se correlated with blood
      Pb and blood Hg and Cu and Zn were correlated to each other in both blood and
      serum. The elements Pt, Pd and Rh, spread in the environment through use of
      catalytic converters in cars, were closely correlated in both blood and serum.
      Apart from the correlations with a probable biological or exposure-related
      explanation, several other correlations, of yet unknown importance and origin,
      were found.

PMID- 12191877
TI  - In vitro toxicity of indium arsenide to alveolar macrophages evaluated by
      magnetometry, cytochemistry and morphological analysis.
AB  - The present study was conducted to clarify the toxicity of Indium arsenide (InAs)
      particles to alveolar macrophages of hamsters by cytomagnetometry, enzyme release
      assays and morphological examinations. One million alveolar macrophages obtained
      from hamsters were exposed to 60 microg of ferrosoferric oxide and 2, 4, 10 and
      20 microg of InAs particles. Relaxation, which is the rapid decline of strength
      of the remanent magnetic fields radiating from the alveolar macrophages, was
      insignificantly delayed and decay constants were not changed due to exposure to
      such doses of InAs. Because the relaxation is thought to be associated with the
      cytoskeleton, the exposure to InAs may not have impaired their motor function. An
      LDH release assay and morphological findings indicate slight damage to
      macrophages. DNA electrophoresis and the TUNEL method revealed neither necrotic
      changes nor apoptotic changes. Thus, InAs particles at such doses hardly cause
      cytostructural changes and cell death.

PMID- 12191878
TI  - Biochemical changes as early stage systemic biomarkers of petroleum hydrocarbon
      exposure in rats.
AB  - Crude and refined petroleum contain a complex mixture of aliphatic, aromatic,
      polyaromatic and heterocyclic hydrocarbon compounds. The objective of our
      research was to investigate early-stage biochemical changes in rats exposed to
      low dosages of petroleum hydrocarbons. The animals were repeatedly exposed, per
      oral by gavage, to low dosages (0.5-2.5 ml/kg) of an Alberta crude oil (ACO) and
      their general health and systemic biochemical parameters were assessed. Rats
      exposed to these doses of ACO did not show any apparent symptoms of intoxication.
      Similarly, no significant changes were observed in clinical parameters of
      systemic impairment. Systemic biochemical assessment has shown that ACO exposure
      caused marked changes in the activities of several cytochrome P-450 (CYP)-linked
      polysubstrate monooxygenase enzymes in liver, kidney and lung tissues. Exposure
      to ACO caused dose-dependent increases in the hepatic activities of
      ethoxyresorufin-O-deethylase, a CYP 1A1/A2-linked enzyme; pentoxyresorufin-O
      dealkylase, a CYP 2B-linked enzyme, and ethoxycoumarin-O-deethylase, a CYP 2B/1A
      linked enzyme. Temporal assessment showed that these systemic biochemical changes
      were reversible in nature. Analysis of biomarker chemicals provided evidence that
      in exposed animals petroleum hydrocarbons were mainly distributed in the adipose
      tissues.

PMID- 12191879
TI  - GSTM1 polymorphism and styrene metabolism: insights from an acute accidental
      exposure.
AB  - Two workers were accidentally exposed to unusually high styrene concentrations
      (>1000 ppm) for about 30 min. In addition to the main styrene metabolites,
      mandelic acid (MA) and phenylglyoxylic acid (PGA), other minor metabolites,
      including specific mercapturic acids, (R,R)- and (S,R)-N-acetyl-S-(1-phenyl-2
      hydroxyethyl)-L-cysteine [(R,R)-M1 and (S,R)-M1] and (R,R)- and (S,R)-N-acetyl-S
      (2-phenyl-2-hydroxyethyl)-L-cysteine [(R,R)-M2 and (S,R)-M2], 4-vinylphenol
      glucuronide and -sulfate, and phenylglycine, were determined by Liquid
      Chromatography Electrospray Tandem Mass Spectrometry (LC-ESI-MS/MS) in urine
      samples collected 12, 24, 36, 48, 75 and 99 h after the episode. The genotypes of
      microsomal epoxide hydrolase, glutathione-S-transferases M1-1 (GSTM1), T1-1
      (GSTT1) and P1-1 (GSTP1) were characterized by PCR-based methods. The two
      subjects showed similar peak levels of MA and PGA, as well as 4-vinylphenol
      conjugates, whereas mercapturic acids were five times higher in the subject
      bearing the GSTM1pos than in the GSTM1null subject. Also, relative proportions of
      diasteroisomers of mercapturic acids were influenced by the GSTM1 polymorphism.

PMID- 12191880
TI  - Polymorphism of glutathione S-transferases and susceptibility to acrylonitrile
      and dimethylsulfate in cases of intoxication.
AB  - In this paper, the difficulties of genetic screening of occupationally exposed
      subjects for the evaluation of retrospective, and prospective, health risk
      assessments is illustrated with reference to glutathione S-transferase (GST)
      function. Individual differences in the magnitude and half-life of adduct levels,
      derived from background and occupational exposure, are observed largely
      independently of genetically determined conjugator status. During detoxification,
      GSTs play a critical role in providing protection against electrophiles and
      products of oxidative stress. GSTs are a superfamily of enzymes that may have
      broad and overlapping substrate specificities. Deficiencies of GST isoenzymes may
      be compensated by the presence of other isoforms and by the use of alternative
      metabolic pathways. This may be one reason for the abundance of controversial
      data on GST polymorphisms and adverse health effects.

PMID- 12191881
TI  - Biomarkers of oxidative stress after controlled human exposure to ozone.
AB  - This study was aimed at evaluating whether controlled short-term exposure to
      ozone (O(3)) induces changes in biomarkers of lung inflammation and oxidative
      stress in exhaled breath condensate (EBC) and blood of healthy subjects. Twenty
      two volunteers were exposed to 0.1 ppm of O(3) for 2 h while performing moderate
      intermittent exercise. EBC and blood were collected before, immediately after and
      18 h after exposure. Changes in biomarkers were measured both in EBC and blood,
      without significant alterations of lung function tests. Changes in EBC, but not
      in blood, were mainly accounted for by a subgroup of 'susceptible' individuals
      bearing the wild genotype for NAD(P)H:quinone oxidoreductase (NQO1) and the null
      genotype for glutathione-S-transferase M1 (GSTM1). Thus, a single 2-h exposure to
      0.1 ppm of O(3) induces changes in biomarkers of inflammation and oxidative
      stress. Polymorphic NQO1 and GSTM1 act as modifier of the lung response to O(3).

PMID- 12191882
TI  - Disposition and metabolism of 1,6-dimethylnaphthalene in rats.
AB  - The distribution, excretion and metabolism of 1,6-dimethylnaphthalene following
      i.p. administration of a single dose of 20 mg/kg to rats, was investigated using
      radiotracer [3H] and a gas chromatography-mass spectrometry technique (GC-MS).
      After 72 h, about 94% of the given dose was excreted in urine and feces. In
      organs and tissues, the highest concentration during the first hours after
      administration was detected in fat, liver, spleen and kidneys. Then gradual
      decline of tritium was noticed in all examined tissues. In urine, the following
      substances were identified and quantified by GC peak areas: unchanged 1,6
      dimethylnaphthalene, 1-methyl-hydroxynaphthalenes, 1-hydroxymethyl-6
      methylnaphthalene, 1,6-dimethyl-thionaphthalene, 6-methyl-1-naphthoic aldehyde, 6
      methyl-1-naphthoic acid, 1,6-dimethyl-thionaphthalene and 1,6-dimethyl
      methylthionaphthalene.

PMID- 12191883
TI  - Effects of inhaled 1-bromopropane vapor on rat metabolism.
AB  - Wistar male rats were exposed to 1-bromopromane (1-BP) vapor for 6 h a day, 5
      days a week, for 3 and 4 weeks (1500 ppm) and 1 day, and 4 and 12 weeks (700
      ppm). After the exposures, 1-BP and its metabolites were measured temporally. In
      the samples obtained from the 700 ppm exposures, hematological and biochemical
      examinations in blood and measurements of hepatic cytochromes P450 were carried
      out. 1-BP in blood decreased rapidly to the detection limit within 0.7 h. On the
      other hand, bromine ion persisted longer in both blood and urine; the biological
      half-life of bromine ion was 4.7-15.0 days in blood and 5.0-7.5 days in urine.
      Glycidol was detected in the urine samples. Based on the experimental results,
      the metabolic pathway of 1-BP was discussed. Hepatic cytochromes P450, aspartate
      aminotransferase (AST) and alanine aminotransferase (ALT) in blood decreased
      significantly with 1-BP exposure, but other enzyme activities did not differ
      significantly.

PMID- 12191884
TI  - Acute and subacute nephrotoxicity of 2-bromophenol in rats.
AB  - The present report aims at providing broader information on the acute
      nephrotoxicity of 2-bromophenol (2-BP) (a bromobenzene (BB) metabolite), due to
      its action on the kidneys, after repeated administration. Investigations were
      performed on female rats. Following a single dose, the most pronounced changes
      involved: concentrations and rates of excretion of proteins in urine, the number
      of epithelial cells excreted in urine, creatinine and urea clearance and reduced
      glutathione in renal tissue. Immediate effects could be ascribed to both renal
      tubules and glomeruli, mirrored in the level of urinary proteins and intensified
      excretion of renal epithelial cells. Less pronounced changes of the indicator
      values were noted under repeated dosing of 2-BP. The results obtained in a single
      exposure study confirm earlier reports on the mild nephrotoxicity of 2-BP
      following exposure to high doses. However, the transition from single to repeated
      exposure does not result in enhanced nephrotoxicity.

PMID- 12191885
TI  - Analysis of pesticides and PCB congeners in serum by GC/MS with SPE sample
      cleanup.
AB  - This paper describes a simple procedure for the quantitative analysis of 25
      polychlorinated biphenyl congeners (PCB) in serum. They are PCB 70, 74, 77, 87,
      99, 101, 118, 126, 128, 138, 151, 153, 156, 169, 170, 180, 183, 187, 191, 194,
      205, 206, 208 and 209. In addition, 15 pesticides are analyzed in the same
      extract: aldrin, p,p'-DDE, p,p'-DDT, dieldrin, endrin, endosulfan I, heptachlor,
      hexachlorobenzene, alpha-hexachlorocyclohexane, beta-hexachlorocyclohexane,
      lindane, methoxychlor, mirex, pentachlorobenzene, and 1,2,3,4-tetrachlorobenzene.
      The procedure involved sample cleanup using a combination of C18 and NH(2) solid
      phase extraction cartridges. The instrumental technique was gas
      chromatography/mass spectrometry with both electron ionization and negative
      chemical ionization in the selected ion monitoring mode. Concentration of sub
      ng/ml level was attainable with 2 ml of serum sample.

PMID- 12191886
TI  - LC-MS determination of urinary toluenediamine in workers exposed to
      toluenediisocyanate.
AB  - To improve the biological monitoring method for 2,6- and 2,4-toluenediisocyanate
      (TDI) exposure, we developed a simple and rapid method for analysis of the
      corresponding urinary metabolites, 2,6- and 2,4-toluenediamine (TDA) using liquid
      chromatograph-mass spectrometry (LC-MS). One ml of urine was hydrolyzed at 100
      degrees C for 1.5 h with H(2)SO(4). Alkalinized hydrolysate was extracted with
      dichloromethane (DCM) and analyzed by atmospheric pressure chemical ionization
      (APCI) LC-MS, in positive-ion mode. The mass spectra of TDA isomers showed the
      protonated molecule [M+H](+), at m/z 123 as the base peak. Calibration curves of
      2,6-TDA were linear up to 400 microg/l. TDA isomers in urine of exposed workers
      as determined by LC-MS correlated well with those obtained by gas chromatography
      mass spectrometry. 2,6- and 2,4-TDA were not detected in non-exposed subjects,
      whereas exposed workers showed urinary levels up to 250 and 63 microg/l,
      respectively.

PMID- 12191887
TI  - Dermal exposure to aqueous solutions of N-methyl pyrrolidone.
AB  - N-methyl pyrrolidone (NMP) is a substance widely used for its strong and
      selective solvent capacity. The strong potential NMP has for skin absorption
      makes biological monitoring ideal for exposure assessment. This study looked at
      brief exposures to NMP in aqueous solutions over a range of concentrations. Two
      volunteers placed one hand in NMP solutions ranging from 5 to 25% for as long as
      15 min followed by urine collection for 48 h. The analyte of interest (analysed
      by GC-MS) was the NMP metabolite 5-hydroxy-N-methyl pyrrolidone (5-HNMP).
      Excretion of 5-HNMP was plotted against time and this showed that urine
      concentrations were at a maximum after about 10 h and 5-HNMP excretion continued
      for 48 h after exposure. The half-life of excretion was found to be approximately
      11 h. The mean correlation between exposure (as a measure of exposure duration
      and solution concentration) and total 5-HNMP excreted was 0.9297.

PMID- 12191888
TI  - Biological monitoring of nitroglycerin exposure by urine analysis.
AB  - Historically biological monitoring to assess exposure has been difficult due to
      the rapid half-life of NG. However, the recent development of a method to assess
      NG and its metabolites (glycerol dinitrates, GDNs) in urine has made biological
      monitoring more feasible. The data reported here result from samples taken from
      three sites using NG. Two of the sites are munitions manufacturing sites and the
      other site is a pharmaceutical manufacturing site. The range of urinary GDN
      concentrations found in the samples at the two munitions sites were 0.9-18, and 0
      4.7 micromol/mol creatinine, and at the pharmaceutical site were 0-0.9
      micromol/mol creatinine). The presence of nitroglycols in the urine of workers
      despite the use of personal protective equipment and local exhaust ventilation
      shows the usefulness of biological monitoring to assess the efficacy of any
      controls in place and the potential of dermal absorption of NG.

PMID- 12191889
TI  - Alcohol and urinary 2-thiothiazolidine-4-carboxylic acid.
AB  - The aim of this work was to study the effect of alcohol on the excretion
      characteristics of urinary 2-thiothiazolidine-4-carboxylic acid (TTCA) in people
      exposed to carbon disulfide (CS(2)) and in non-exposed subjects. Ten male non
      exposed volunteers consumed 150, or 250 ml, of liquor (38 degrees ) and the
      excretion dynamics of urinary TTCA were detected by HPLC. A questionnaire and
      urinary TTCA analyses were conducted in 152 male workers exposed to CS(2) and 60
      male controls. CS(2) concentrations at the workplace were measured by GC. Results
      showed that urinary TTCA levels in non-exposed volunteers reached a high peak 3 h
      after drinking 150 ml liquor, which returned 12 h later to the levels before
      drinking; TTCA levels were in accordance with the quantity of alcohol consumed.
      There were increasing tendency of urine TTCA levels in workers exposed to
      different concentrations of CS(2) (<or=10 ppm, >10 ppm). TTCA levels in people
      with drinking habits seemed higher in the non-exposed group than in the exposed
      group, especially in those exposed over 10 ppm. The results suggest that the
      consumption of liquor in large quantities may interfere with the levels of
      urinary TTCA. Thus, in biomonitoring of CS(2) a suitable sampling time is
      important to avoid a biased estimation of CS(2) exposure.

PMID- 12191890
TI  - Comparison of urinary bromide levels among people in East Asia, and the effects
      of dietary intakes of cereals and marine products.
AB  - Groups of people with no occupational exposure to Br-containing chemicals (29-54
      year old, mostly women) in Japan, China and Korea, respectively, offered spot
      urine samples. Those in China and Korea offered 24 h duplicates of foods of the
      day. Urine samples were analyzed for Br by ECD-gas chromatography (ECD-GC) after
      derivatization to methyl bromide, and the Br-U was adjusted for a specific
      gravity of 1.016. Food intake data were based on national statistics and
      supplemented by the food duplicate data. Mean Br-U was 5.4 and 6.5 mg/l for
      Japanese men and women, respectively. Mean levels were in a range of 1.8-2.8 mg/l
      for four groups of Chinese, and 8-12 mg/l for the four groups of women in Korea.
      Br-U levels among Korean women were close levels reported for occupational
      exposure to 1- or 2-bromopropane, or methyl bromide. Regression analyses showed
      that Br-U levels were influenced by the intake of marine products (such as sea
      algae, sea fish and shellfish) and fruits, and inversely relate to intakes of
      cereals and potato.

PMID- 12191891
TI  - Butoxyethoxyacetic acid, a biomarker of exposure to water-based cleaning agents.
AB  - The aim of the study was to investigate the suitability of butoxyethoxyacetic
      acid (BEAA) as a biomarker of exposure to water-based cleaning agents containing
      diethylene glycol mono butyl ether (DEGBE). The study was performed in two
      printing plants where water-based products containing 10-15% DEGBE were used for
      rubber and blanket washes. Thirty nine newspaper pressroom workers (exposed) and
      19 employees of newspaper despatch departments (controls) were investigated. By
      questionnaire, the workers were asked about the use of personal protective
      measures. BEAA was determined in post-shift urine using GC-MS. The BEAA
      concentration in the urine of exposed workers ranged up to 75.1 mg/l (median 6.3
      mg/l), whereas in urine samples of the controls the BEAA level was below or
      around the determination limit of 0.5 mg/l. A protective effect on DEGBE uptake
      was observed with the use of protective gloves. This observation implies that
      dermal penetration of DEGBE may be important in exposure monitoring.

PMID- 12191892
TI  - Construction of a database of benzene biological monitoring.
AB  - Biological monitoring of occupational exposure to benzene has been conducted in
      the petroleum, steel and chemical industries. The urinary benzene-specific
      biomarker, S-phenylmercapturic acid (PMA), was quantified in post-shift samples
      using a sensitive enzyme-linked immunosorbent assay (ELISA) and expressed as a
      function of urinary creatinine concentration. The assay, based on a PMA-specific
      antiserum, is sufficiently sensitive to measure PMA levels in non-occupationally
      exposed control subjects. The assay delivers batch results in a timely manner
      which may be as short as 3 h. Samples were analysed from groups of workers
      engaged in coke oven combustion processes, petroleum refining and decontamination
      of a benzene land spill. The construction of a database of results provides an
      index of benzene uptake as a consequence of the respective work processes and
      tasks and readily enables benchmarking exercises aimed at comparing degrees of
      exposure across segments of industry.

PMID- 12191893
TI  - BIOMarkers for occupational diesel exhaust exposure monitoring (BIOMODEM)--a
      study in underground mining.
AB  - Methods for the assessment of exposures to diesel exhaust were evaluated,
      including various biomarkers of internal exposure and early biological effects.
      The impact of possible biomarkers of susceptibility was also explored.
      Underground workers (drivers of diesel-powered excavators) at an oil shale mine
      in Estonia were compared with surface workers. Personal exposures to particle
      associated 1-nitropyrene (NP) were some eight times higher underground than on
      the surface. Underground miners were also occupationally exposed to benzene and
      polycyclic aromatic hydrocarbons, as indicated by excretion of urinary
      metabolites of benzene and pyrene. In addition, increased O(6)-alkylguanine DNA
      adducts were detected in the white blood cells of underground workers, suggesting
      higher exposure to nitroso-compounds. However, no differences between underground
      and surface workers were observed in the levels of other bulky DNA adducts
      determined by 32P-postlabelling, or in DNA damage. The study indicated that
      smoking, diet and residential indoor air pollution are important non-occupational
      factors to consider when interpreting biomonitoring results.

PMID- 12191894
TI  - Urinary hydroxyproline as a biomarker of effect after exposure to nitrogen
      dioxide.
AB  - A cross-sectional study was carried out on two groups of subjects differently
      exposed to nitrogen dioxide in order to test the urinary hydroxyproline ratio
      (UHP/mg/24 h/m(2)) as a biomarker of effect after exposure to this pollutant. UHP
      was determined in samples of 58 subjects divided into two groups comparable to as
      lifestyle and training. The first group was composed of 29 subjects who used to
      do jogging in urban areas polluted by nitrogen dioxide. The second group was made
      up of 29 subjects who used to do jogging in non-polluted countryside areas. The
      mean concentration of UHP of urban joggers was 25.02+/-9.21 mg/24 h/m(2), whereas
      in those training in the countryside it was 13.78+/-6.68 mg/24 h/m(2). Thus, UHP
      was higher in subjects training in areas polluted by nitrogen dioxide than in the
      subjects training in non-polluted areas.

PMID- 12191895
TI  - Comparative pathogenicity of three genetically distinct types of Trypanosoma
      congolense in cattle: clinical observations and haematological changes.
AB  - The pathology of African bovine trypanosomosis was compared in Zebu cattle
      subcutaneously inoculated with three clones of trypanosomes corresponding to the
      three genetically distinct types of Trypanosoma congolense; savannah-type, west
      African riverine/forest-type and kilifi-type. All inoculated animals became
      parasitaemic between 7 and 11 days post-infection (dpi). The savannah-type showed
      consistently higher levels of parasitaemia and lower packed red cell volume
      percentages and leukocyte counts than the other two types. The syndrome was also
      more severe in the savannah-type and led inexorably to death between 29 and 54
      dpi while animals with the forest or the kilifi-types recovered from earlier
      symptoms and haematological alterations after 3 months of infection. By the end
      of the experiment, the animals self-cured from the forest-type infection and the
      kilifi-type passed under control. The results of the present study indicated
      clear difference in pathogenicity between the three types of T. congolense; the
      savannah-type was virulent while the forest-type was of low pathogenicity and the
      kilifi-type was non-pathogenic.

PMID- 12191896
TI  - Experiments on transmission of an unidentified Theileria sp. to small ruminants
      with Haemaphysalis qinghaiensis and Hyalomma anatolicum anatolicum.
AB  - Experiments on the transmission of an unidentified Theileria sp. infective for
      small ruminants by Haemaphysalis qinghaiensis and Hyalomma anatolicum anatolicum
      were carried out. Three Theileria-free batches of adult, larvae, and nymphs of
      laboratory reared H. qinghaiensis and Hy. a. anatolicum ticks were infected by
      feeding them on sheep infected with Theileria sp. The Theileria sp. was
      originally isolated from adult ticks of H. qinghaiensis, by inoculation of blood
      stabilates or tick transmission. H. qinghaiensis has been shown to be capable of
      transmitting the Theileria sp. infective for small ruminants transstadially to
      sheep and goats. The nymphs developed from the larvae engorged on the sheep
      infected with the parasite transmitted the pathogen to splenectomized sheep with
      prepatent periods of 30, 31 days, respectively; but the subsequent adult ticks of
      H. qinghaiensis derived from the nymphs did not transmit the pathogen to sheep.
      However, adults developed from the nymphs engorged on the sheep infected with the
      parasite transmitted the pathogen to sheep with prepatent periods of 24-27 days.
      The larvae, nymphs and adult ticks derived from female H. qinghaiensis ticks
      engorged on infected sheep were not able to transmit the parasite transovarially.
      The same experiments were done with Hy. a. anatolicum, but examination for
      presence of piroplasma of Theileria sp. from all animals were negative,
      demonstrating that Hy. a. anatolicum could not transmit the organism to sheep or
      goats.

PMID- 12191897
TI  - The prevalence of porcine cysticercosis in Eastern and Southern provinces of
      Zambia.
AB  - The objective of this study was to determine the prevalence and importance of
      porcine cysticercosis in rural areas of Zambia. The study involved an abattoir
      survey of 1316 pigs at a slaughter slab in Lusaka and two field surveys in
      villages in Southern and Eastern provinces. Lingual examination of live pigs and
      visual inspection of their carcass as well as blood sampling for measuring
      circulating parasite antigen by enzyme-linked immunosorbent assay (Ag-ELISA) were
      used as parameters to measure infection. In the field surveys, a questionnaire
      was administered to every household whose pigs were examined to obtain
      information on pig husbandry practices and to study risk factors for the
      infection. Out of the 1316 pigs examined at the slaughter slab, 143 (10.9%) and
      271 (20.6%) were positive by lingual examination and meat inspection,
      respectively. Most of the pigs were very heavily infected with predominantly live
      cysts. The field surveys revealed that eight (8.2%) out of 98 pigs from Southern
      province and eight (5.2%) out of 151 pigs from Eastern province were positive for
      cysticercosis by tongue palpation. Using the Ag-ELISA 20 (20.8%) and 14 (9.3%)
      pigs were positive in Southern and Eastern provinces, respectively. The
      questionnaire survey revealed poor pig husbandry practices, absence of meat
      inspection and control, poor knowledge of the disease and poor sanitation in the
      surveyed villages. The prevalence of pig cysticercosis found in this study ranks
      among the highest in the southern African region, in Africa and in the world. The
      current study suggests the presence of human tapeworm carriers and a high risk of
      human cysticercosis in the surveyed areas as well as in urban centres where pigs
      from rural areas are increasingly sold, slaughtered and consumed.

PMID- 12191898
TI  - Castration and pregnancy of rural pigs significantly increase the prevalence of
      naturally acquired Taenia solium cysticercosis.
AB  - Cuentepec is a rural village of central Mexico, where 1300 pigs were bred at the
      time of the study in conditions that favor Taenia solium transmission. The
      tongues of 1087 (84%) of these pigs were visually examined and 33% were found to
      be cysticercotic. Castration of male pigs increased prevalence from 23 to 50% (P
      < 0.001) and pregnancy in sows also increased their prevalence from 28 to 59% (P
      < 0.001). Thus, endocrinological conditions characterized by low levels of
      androgens or high levels of female hormones probably influence the susceptibility
      of pigs to T. solium cysticercosis as observed in mice infected with Taenia
      crassiceps. Delaying castration of male pigs and confinement of sows during
      pregnancy might significantly decrease the prevalence of pig-cysticercosis and
      help curb transmission without much cost or difficulty.

PMID- 12191899
TI  - Taenia solium oncosphere antigens induce immunity in pigs against experimental
      cysticercosis.
AB  - Immunity to Taenia solium infection was investigated using an experimental
      intramuscular oncosphere infection assay (IMOA) model in pigs. Three naturally
      infected pigs with cysticercosis were treated with oxfendazole (OFZ), a drug
      demonstrated to kill cysts in porcine muscle. These animals were then challenged
      with oncospheres but did not develop any cysts while three uninfected pigs that
      were similarly challenged, did develop intramuscular cysts. In another study, two
      groups of three pigs each were immunized with crude T. solium oncosphere and
      metacestode antigens, respectively, and tested with the IMOA. Immunization with
      crude oncosphere antigens (OAs) induced 100% protection, while metacestode
      antigens provided only partial protection. Immunoblots showed that pigs with
      complete immune protection to oncosphere intramuscular challenge had antibodies
      to two OAs at 31.3 and 22.5 kDa, respectively. Antibody to these two antigens was
      absent in pigs immunized with metacestodes or in uninfected control pigs. This
      study demonstrated the presence of two antigens that are unique to the
      oncosphere. Although, antibody to these two antigens is consistently present in
      pigs that are protected from an oncosphere intramuscular challenge their role in
      preventing infection by T. solium larval cysts is still hypothetical.

PMID- 12191900
TI  - Chemotherapy of porcine cysticercosis with albendazole sulphoxide.
AB  - Cysticercosis is a zoonotic disease of humans produced by the larval stage of
      swine parasite, Taenia solium. Chemotherapy of infected pigs is a possible
      strategy for avoiding disease transmission and improving health programs in
      endemic areas of cysticercosis. In this preliminary study, seven naturally
      infected pigs from 6 to 12 months of age were allotted to treated (n = 4) and
      control groups (n = 3). The treated animals received a subcutaneous injection in
      their forelegs and thighs of 15 mg/kg per body weight of albendazole sulphoxide
      (ABZSO; Pisa, Mexico) once per day for 8 days. At the same time, the control
      group received a subcutaneous injection of saline solution (9% NaCl). After 12
      weeks, all the animals were slaughtered and at least 200 metacestodes were
      isolated from the muscles and brain of each animal. Using histology and the
      metacestode viability criteria described in this study, treated animals had no
      viable cysts in their muscle (0/200), while 7 of 17 (41.1%) viable cysts were
      observed in those isolated from their brains. In the control group, 183/200
      (91.5%) muscle metacestodes were viable and from brain, 22/29 (75.8%)
      metacestodes were viable. The 15 mg/kg per body weight dosage of ABZSO was 100%
      effective against muscular cysticercosis as shown by the lack of viable cysts and
      the micro-calcifications in meat from the treated pigs.

PMID- 12191901
TI  - Dose confirmation studies of moxidectin 1% non-aqueous injectable and moxidectin
      0.5% pour-on formulations against experimentally induced infections of larval and
      adult stage Oesophagostomum radiatum and Trichuris discolor in cattle.
AB  - Separate controlled trials were conducted to evaluate the efficacy of two
      formulations of moxidectin (1% non-aqueous injectable solution and 0.5% pour-on
      (Cydectin) against larval or adult stages of Oesophagostomum radiatum and
      Trichuris discolor infecting cattle. Fifty-three strongylate-free dairy breed
      steer calves were obtained from commercial sources. After a brief acclimation
      period, calves were randomly divided into two pools to evaluate the efficacy of
      the moxidectin formulations against targeted larval (n = 27 calves) or adult (n =
      26 calves) parasites. Calves in the larvacidal trial were inoculated on Day -16
      relative to treatment with approximately 1000 embryonated Trichuris spp. eggs and
      approximately 640 infective Oesophagostomum spp. larvae. Calves were allocated by
      lottery to one of three treatment groups (n = 8 per group), which included: Group
      1--moxidectin 0.5% pour-on (0.5 mg/kg body weight (BW)) applied topically; Group
      2--moxidectin 1% non-aqueous injectable (0.2 mg/kg BW) administered
      subcutaneously; Group 3--untreated controls. Treatments were administered on Day
      0 and calves were housed by group with no contact among animals of different
      treatments. Three sentinel calves were necropsied on Day 0 of the larvacidal
      trial to assess viability of larval inocula. On Days 14, 15 and 16 after
      treatment, calves were euthanatized (two or three from each group per day) and
      samples of gut contents were collected for determination of total worm counts. On
      Day -63 relative to treatment, calves in the adulticidal efficacy trial were
      inoculated with approximately 1000 embryonated Trichuris eggs and then on Day -35
      with approximately 2500 infective Oesophagostomum spp. larvae. Fecal samples were
      collected on Day -7 and the 24 calves with the highest egg counts were assigned
      by lottery to the following three treatment groups (n = 8 per group): Group 4-
      moxidectin 0.5% pour-on; Group 5--moxidectin 1% injectable; Group 6--untreated
      controls. Details of experimental treatments, calf housing and necropsy
      scheduling were similar to the larvacidal trial. In both the larvacidal and
      adulticidal trials, inocula contained a variety of parasites in addition to the
      targeted species. Based on geometric means, both moxidectin 0.5% pour-on and
      moxidectin 1% non-aqueous injectable significantly reduced (P < 0.05) numbers of
      Oesophagostomum spp. and Trichuris spp. with anthelmintic efficacies of >99% when
      used against adult or larval stages of infection. In addition, both formulations
      of moxidectin demonstrated >95% efficacy (P < 0.05) against larval stages of
      Strongyloides papillosus. The pour-on formulation had >97% adulticidal and
      larvacidal efficacy against Cooperia spp. females, while the injectable product
      was effective against female Cooperia spp. larvae and Cooperia oncophora adult
      males.

PMID- 12191902
TI  - Detection of circulating hypodermin C: an antigen capture ELISA for diagnosis of
      cattle grub (Diptera: Oestridae) infestations.
AB  - An antigen capture assay for the detection of circulating hypodermin C was
      developed for diagnosis of hypodermosis. A murine monoclonal antibody to
      recombinant hypodermin C was raised using rapid immunization and a one-step
      hybridization-cloning technique. A highly reactive, specific monoclonal antibody
      was tested using sera spiked with known quantities of purified, native hypodermin
      C or with recombinant hypodermin C. Sensitivity of 96.4% and specificity of 95.6%
      for the antigen capture assay was assessed using a panel of sera from animals
      unexposed to cattle grubs and from cattle with palpation proven cattle grub
      infestations. Data from this panel of sera was used to establish the cut-off OD
      for further testing. The kinetics of circulating hypodermin C was assessed using
      the assay in three groups of cattle artificially infested with 50, 100 or 200
      first instar Hypoderma lineatum. Antigen was first detected approximately 6 weeks
      after infestation. The amount of antigen detected increased in each group of
      animals reaching peaks at different times in each group. Levels of antigen fell
      quickly following arrival of grubs at the back and completion of the molt to
      second instar.

PMID- 12191903
TI  - Tube morphogenesis.

PMID- 12191904
TI  - Regulating the clathrin-coated vesicle cycle by AP2 subunit phosphorylation.
AB  - Clathrin-coated pits form from the concerted assembly of many different protein
      components that interact with each other and with the lipid bilayer. When the
      coated pit pinches off to form a coated vesicle, the coat is removed to allow
      fusion of the endocytic vesicle with an early endosome, and the disassembled coat
      components can then recycle through the cytosol to participate in new rounds of
      coated pit formation. One potential mechanism to regulate the cycles of coat
      protein assembly and disassembly is reversible phosphorylation, particularly
      given that many of the coat components, such as the AP2 adaptor complex, are
      phosphorylated on multiple sites both in vitro and in vivo. Recent studies have
      provided particular insight into the role of phosphorylation of the cargo-binding
      micro2 subunit of AP2.

PMID- 12191905
TI  - The barrier function of skin: how to keep a tight lid on water loss.
AB  - Without an epidermis, we would be in a sorry state. The epidermal layer not only
      protects us from environmental pathogens but also acts as a 'barrier' to water
      loss. The identification of the molecular nature of the barrier has occupied the
      efforts of skin researchers over many years, with the consensus in the field
      being that a protein-lipid layer, located in the upper layers of the epidermis,
      is necessary for establishment and maintenance of a water barrier. Now, evidence
      has been presented that components of intercellular junctions, termed tight
      junctions, also play an essential role in development of barrier function in the
      skin. Remarkably, the data support a hypothesis that was presented more than 30
      years ago.

PMID- 12191912
TI  - Multivesicular bodies: a mechanism to package lytic and storage functions in one
      organelle?
AB  - Multivesicular bodies (MVBs) are endosomes or prevacuolar compartments. The
      lumens of their internal vesicles are thought to be topologically equivalent to
      cytoplasm and their membranes direct proteins and lipids for degradation. Here,
      we describe a new MVB function; in certain plant MVBs, the internal vesicles
      contain lytic enzymes and the surrounding 'soup' is a storage compartment.
      Separate vesicular pathways deliver proteins to the storage and lytic
      compartments. Recent data indicate that mammalian secretory lysosomes also have
      two compartments served by separate vesicular pathways. The formation of separate
      storage and lytic compartments within MVBs poses problems for membrane
      organization and topology that have not previously been considered in the
      literature. We offer a hypothetical model to address these problems.

PMID- 12191913
TI  - The CDM protein DOCK2 in lymphocyte migration.
AB  - T and B lymphocytes migrate hundreds of micrometers each day to survey the body's
      lymphoid tissues for antigens. No other mammalian cell type undergoes such
      extensive and continual movement, raising the question of whether lymphocytes
      have specializations to support their migratory behavior. This possibility has
      recently gained support from studies of mice deficient in DOCK2, a member of the
      Caenorhabditis elegans Ced-5, mammalian DOCK180 and Drosophila melanogaster
      myoblast city (CDM) family of scaffolding proteins. Migration of lymphocytes, but
      not other cell types, is severely disrupted in DOCK2-deficient mice. Despite the
      conserved role of CDM molecules in regulating Rac activation and actin assembly,
      relatively little is known about how these molecules function. Here, we review
      the role of DOCK2 in lymphocyte homing to lymphoid tissues and discuss recent
      findings for other CDM family molecules that provide a basis for understanding
      how DOCK2 might function in lymphocytes.

PMID- 12191914
TI  - Altered trafficking and epithelial cell polarity in disease.
AB  - Establishment and maintenance of a polarized epithelium relies on the integration
      of signaling cascades, acquisition of specialized trafficking circuits and
      establishment of a unique cytoarchitecture. Defects in any of these processes can
      adversely affect cell polarity and cause defects in specific organs and systemic
      disease. Mutations that disrupt the proper transport of individual plasma
      membrane proteins, or inactivate components of the epithelial-specific
      trafficking machinery, have severe functional consequences. Links between renal
      diseases and defects in trafficking, differentiation or signaling, highlight the
      delicate balance between these parameters which, when altered, precipitates a
      loss of renal function.

PMID- 12191915
TI  - The inner lives of focal adhesions.
AB  - In focal adhesions of eukaryotic cells, transmembrane receptors of the integrin
      family and a large set of adaptor proteins form the physical link between the
      extracellular substrate and the actin cytoskeleton. During cell migration,
      nascent focal adhesions within filopodia and lamellipodia make the initial
      exploratory contacts with the cellular environment, whereas maturing focal
      adhesions pull the cell forward against the resistance of 'sliding' focal
      adhesions at the cell rear. Experimental approaches are now available for
      analysing the dynamics and interior structure of these different focal adhesions.
      Analysing focal-adhesion dynamics using green-fluorescent-protein-linked integrin
      leads us to propose that the acto-myosin-controlled density and turnover of
      integrins in focal adhesions is used to sense the elasticity and spacing of
      extracellular ligands, regulating cell migration by mechanically transduced
      signaling.

PMID- 12191916
TI  - Tubulogenesis in the developing mammalian kidney.
AB  - How do fibroblasts spontaneously organize into a polarized epithelial tube? This
      question has fascinated scientists studying the mammalian kidney for more than 40
      years. The formation of epithelial tubules in the developing mammalian kidney
      involves both the aggregation of mesenchymal cells and their conversion into
      polarized epithelium, as well as the growth and branching morphogenesis of
      existing epithelium. The interactions among mesenchyme, epithelia and, more
      recently, the stroma, have been well characterized and provide novel insights
      into the regulatory mechanisms underlying complex organ development. Cell
      signaling pathways and transcription factors have been defined through genetic
      and biochemical assays such that a picture of early kidney tubulogenesis is
      beginning to emerge.

PMID- 12191919
TI  - A comparison of imaging methods for use in an array biosensor.
AB  - An array biosensor has been developed which uses an actively-cooled, charge
      coupled device (CCD) imager. In an effort to save money and space, a
      complementary metal-oxide semiconductor (CMOS) camera and photodiode were tested
      as replacements for the cooled CCD imager. Different concentrations of CY5
      fluorescent dye in glycerol were imaged using the three different detection
      systems with the same imaging optics. Signal discrimination above noise was
      compared for each of the three systems.

PMID- 12191920
TI  - Glow-discharge treated piezoelectric quartz crystals as immunosensors for HSA
      detection.
AB  - The aim of this study is to develop an immunoaffinity sensor based on
      piezoelectric crystals for human serum albumin (HSA) detection in aqueous media.
      Quartz crystals were treated with ethylene diamine (EDA) plasma in a glow
      discharge apparatus in order to substitute amino groups on their surfaces. Then
      anti-HSA antibodies were immobilized via these amino groups by using
      glutaraldehyde (GA) as cross-linker. Immobilization of the antibody on the quartz
      crystal was examined for different pH, antibody concentration and treatment time.
      The optimum conditions for anti-HSA immobilization were evaluated by the
      measurements of the activity of the surface against HSA. The optimum values of
      pH, antibody concentration and treatment time were found 6.2, 0.15 mg/ml and 2 h,
      respectively. For detection of HSA into the solution, two methods were used. In
      the first (dip and dry) method, the frequency shifts were measured in air after
      the 1 h interaction of the anti-HSA immobilized crystals with HSA solution. In
      the other (direct) method, the frequency shifts were followed continuously for 60
      min. while the probe was immersed in the HSA solution. An increase for the
      frequency shifts was observed with increasing of HSA concentration of 16-128
      microg/ml. Both the immobilization and antibody-interaction conditions were found
      important on the extend of these specific interaction. The relations between the
      HSA concentrations and frequency shifts were exponential in both methods.

PMID- 12191921
TI  - Optimisation of the enzyme-based determination of hydrogen peroxide using the
      quartz crystal microbalance.
AB  - The benzidines, 3,3'-diaminobenzidine (DAB), 3,3'-dimethoxybenzidine (DMOB) and
      3,3',5,5'-tetramethylbenzidine (TMB) were enzymatically oxidised to detect
      hydrogen peroxide, using the quartz crystal. The oxidised product mainly remains
      in suspension, resulting in a limited quartz sensor signal. We have used two non
      ionic surfactants, Tween 80 and Triton X-100 to interact with the oxidised
      amphiphilic products to increase their solubility and surface activity, and their
      ability to adsorb to the crystal surface. Tween 80 exhibits optimised response
      effects for DAB, DMOB and TMB at 0.012, 0.005, and 0.002% (v/v), respectively,
      whereas Triton X-100 is optimum at 0.1, 0.2, and 0.006% (v/v), respectively. As a
      result, we have improved the quartz crystal sensor sensitivity to peroxide. The
      use of Triton X-100 gave an improved response time.

PMID- 12191922
TI  - Direct electrochemistry of hemoglobin in egg-phosphatidylcholine films and its
      catalysis to H(2)O(2).
AB  - Direct electrochemistry of hemoglobin was observed in stable thin film composed
      of a natural lipid (egg-phosphatidylcholine) and hemoglobin on pyrolytic graphite
      (PG) electrode. Hemoglobin in lipid films shows thin layer electrochemistry
      behavior. The formal potential E degrees ' of hemoglobin in the lipid film was
      linearly varied with pH in the range from 3.5 to 7.0 with a slope of -46.4 mV pH(
      1). Hemoglobin in the lipid film exhibited elegant catalytic activity for
      electrochemical reduction of H(2)O(2), based which a unmediated biosensor for
      H(2)O(2) was developed.

PMID- 12191923
TI  - Surface plasmon resonance and free oscillation rheometry in combination: a useful
      approach for studies on haemostasis and interactions between whole blood and
      artificial surfaces.
AB  - In haemostatic and biomaterial research biological processes at surfaces and in
      the bulk phase of the surface-contacting medium are important. The present work
      demonstrates the usefulness of the combination of surface plasmon resonance
      (SPR), sensitive to changes in refractive index at surfaces, and free oscillation
      rheometry (FOR), sensitive to rheological properties of the bulk, for
      simultaneous real-time measurements on coagulation and fibrinolysis of blood
      plasma and coagulation of whole blood. SFLLRN stimulated coagulation of native
      whole blood presented a higher SPR signal with different appearance than plasma
      coagulation, while the FOR signals corresponding to plasma and whole blood
      coagulation were similar. This indicated that the SPR technique was more
      sensitive to cell-surface interactions than to fibrin formation in whole blood
      during coagulation, while the FOR technique were equally sensitive to coagulation
      in whole blood and plasma. Spontaneous coagulation of native whole blood in
      contact with methyl- and hydroxyl-terminated self-assembled monolayers (SAM) on
      gold and gold surfaces regenerated after coagulation were also studied. The
      regenerated gold surfaces displayed the shortest coagulation times, although the
      contact-activation of blood coagulation for these surfaces was low. The
      methylated and hydroxylated surfaces were comparable in terms of coagulation
      activation, while the hydroxylated surfaces presented FOR signals that indicated
      detaching of the coagulum from the surface. The combination of SPR and FOR is
      well suited for studies of cell- and protein-surface interactions and
      simultaneous bulk processes. Possible applications are investigations of blood
      cell defects in patients and monitoring of native whole blood interactions with
      artificial surfaces.

PMID- 12191925
TI  - A simple exploratory algorithm for the accurate and fast detection of spontaneous
      synaptic events.
AB  - We have developed a program for the fast and accurate detection of spontaneous
      synaptic events. The algorithm identifies each event of which the slope and
      amplitude which meet criteria. The significant feature of this algorithm is its
      stepwise and exploratory search for the onset and the peak points. During the
      first step, the program employing the algorithm makes a rough estimate of the
      candidate for a synaptic event, and determines a 'temporary' onset data point.
      The next step is the detection of the true onset data point and 'temporary' peak
      data point, which probably exist several points after the temporary onset data
      point. The third step is a backward search to detect the true peak data point.
      The final step is to check whether the amplitude of the detected event exceeds
      the threshold. This stepwise and shuttlewise search allows for the accurate
      detection of the peak points. Using this program, we succeeded in detecting an
      increased frequency and amplitude of spontaneous excitatory postsynaptic currents
      in chick cerebral neurons following the application of 12-O-tetradecanoyl-phorbol
      13-acetate (TPA). In addition, we demonstrated that the program employing the
      algorithm was able to be used for the detection of extracellular action
      potentials.

PMID- 12191924
TI  - Comparative studies with surface plasmon resonance and free oscillation rheometry
      on the inhibition of platelets with cytochalasin E and monoclonal antibodies
      towards GPIIb/IIIa.
AB  - In the haemostatic system a multitude of processes are intertwined in fine-tuned
      interactions that arrest bleeding, keep the circulatory system open, and the
      blood flowing. The occurrence of both surface and bulk interactions adds an
      additional dimension of complexity. These insights have led to the belief that
      global overall procedures can inform on the likely behaviour of the system in
      health and disease. Two sensing procedures: surface plasmon resonance (SPR),
      which senses surface interactions, and free oscillation rheometry (FOR), which
      senses interactions within the bulk, have been combined and evaluated. The
      contribution of blood cells, mainly platelets, to the SPR and FOR signals was
      explored by simultaneous SPR and FOR measurement during native whole blood
      coagulation, accelerated via the platelets through addition of SFLLRN peptide and
      inhibition of platelet aggregation with abciximab (ReoPro) and of shape change
      with cytochalasin E. The SPR technique was found to be sensitive to inhibition of
      blood cell functions such as adhesion to and spreading on surfaces, as well as
      platelet aggregation. SPR seemed not to be directly sensitive to fibrin
      polymerisation in coagulating whole blood. The FOR technique detected the
      coagulation as a bulk phenomenon, i.e. the gelation of the blood due to fibrin
      formation was detected. The combination of SPR and FOR may therefore be suitable
      for studies on blood cell functions during coagulation.

PMID- 12191926
TI  - Imaging of electrochemical enzyme sensor on gold electrode using surface plasmon
      resonance.
AB  - Three types of imaging, namely layer structure, electrochemical reaction, and
      enzyme sensor response, were achieved by applying surface plasmon resonance (SPR)
      measurement to an electrochemical biosensor. We constructed glucose oxidase based
      mediator type sensors on a gold electrode by spotting the mediator that contained
      horseradish peroxidase and spin coating the glucose oxidase film. The layer
      structure of the sensor was imaged by means of angle scanning SPR measurement.
      The single sensor spot (about 1 mm in diameter) consisted of about 100 x 100
      pixels and its spatial structure was imaged. The multilayer structure of the
      enzyme sensor had a complex reflectance-incident angle curve and this required us
      to choose a suitable incident angle for mapping the redox state. We chose an
      incident angle that provided the most significant reflection intensity difference
      by using data obtained from two angle scanning SPR measurements at different
      electrode potentials. At this incident angle, we controlled the electrochemical
      states of the spotted mediator in cyclic voltammetry and imaged the degree to
      which the charged site density changed. Finally, we mapped the enzymatic activity
      around the mediator spot by the enzymatic reoxidation of pre-reduced mediator in
      the presence of glucose.

PMID- 12191927
TI  - A hydrogen biosensor made of clay, poly(butylviologen), and hydrogenase
      sandwiched on a glass carbon electrode.
AB  - A hydrogen gas (H(2)) biosensor was developed in which hydrogenase (H(2)ase) was
      immobilized and sandwiched between two layers of a montmorillonite clay and
      poly(butylviologen) (PBV) mixture on a glass carbon electrode. The immobilized
      PBV efficiently enhanced the electron transfer among the electrode, H(2)ase, and
      methyl viologen in solution. Both PBV and methyl viologen acted as the electron
      carrier in the clay-PBV-H(2)ase modified electrode. The clay-PBV-H(2)ase
      electrode catalyzed the oxidation of H(2) to protons (H(+)) with the electrons
      being transferred by viologen groups to the electrode. The activation energy of
      this process was 38+/-2 kJ/mol at pH 7. The catalytic current of the clay-PBV
      H(2)ase electrode increased linearly when exposed to increasing concentrations of
      H(2) gas. In contrast, this electrode showed no activity when exposed to three
      combustible compounds, namely, carbon monoxide, methane and methanol. The optimum
      pH range for the oxidation of H(2) by the clay-PBV-H(2)ase electrode was from 7
      to 10. Electron transfer process in the clay-PBV-H(2)ase electrode is discussed.

PMID- 12191928
TI  - Gold bands as a suitable surface for enzyme immunoassays.
AB  - Gold bands sputtered over a polymeric material, Kapton, are employed for the
      development of enzyme immunoassays. The immunological interaction takes place
      between human IgM and alkaline phosphatase (AP) conjugated anti-IgM. The model
      analyte (IgM) could be determined following a non-competitive design in the range
      of 0.05-5 ppm, with a limit of detection of 50 ppb. After the interaction, gold
      bands are sequentially inserted in a flow system and the extension of the
      reaction is followed through the enzymatic hydrolysis of naphthylphosphate, AP
      substrate. The product, naphthol, is oxidised to naphtoquinone in the gold band
      of the flow cell that constitutes the detector. Parameters affecting the
      interaction are studied and calibration curves are performed. The reproducibility
      between different bands (RSD=4%, n=5) and possibilities of regeneration are also
      detailed.

PMID- 12191929
TI  - A new generation of scanners for DNA chips.
AB  - Today, most of the DNA chips are used with fluorescent markers. Associated with
      fluorescence confocal scanners, this technology achieves remarkable performances
      in terms of sensitivity and accuracy. The main technical issues related to these
      scanners have already been reviewed. However, these scanners are costly,
      especially when high density chips are used. In this case, a mechanical precision
      of 1 microm or less is required to achieve the measurement precision required.
      This cost level prevents the spread of this technology in the diagnostic market.
      We will present a new concept for scanners with equivalent or superior
      performances, with a cost cut of 5-10. This concept is inspired from the field of
      optical disk and reader. Basically, an optical format is added to the chip,
      before DNA deposition. This format contains tracks which are superimposed to the
      DNA features. These tracks define the path that an optical head of a CD player
      must follow in order to scan the surface of the DNA chip. Such a head is a very
      cheap component, and has a precision of less than 100 nm thanks to real-time
      focus and tracking. These functions are fulfilled by electromagnetic actuators
      mounted on the support of the frontal lens. We show here that it is possible to
      use such a head to build a fluorescence confocal scanner with equivalent or even
      better performances than conventional scanners.

PMID- 12191930
TI  - Convenient and rapid detection of pesticides in extracts of sheep wool.
AB  - A relatively simple, rapid extraction technique based on acetonitrile was
      combined with the use of screen-printed electrodes bearing cholinesterases to
      detect organo-phosphate pesticides from an otherwise intractable matrix, sheep
      wool. It proved possible to separate, for convenience, the exposure of the
      electrodes from measurement of their (inhibited) activity. The electrodes were
      used once and then discarded. Estimation of the extent of inhibition is dependent
      on reference to the activity of control electrodes. The presence of pesticides in
      the extracts could be detected with any of three commonly available
      cholinesterases but the most sensitive enzyme was butyryl cholinesterase from
      horse serum.

PMID- 12191931
TI  - An ISFET-based immunosensor for the detection of beta-Bungarotoxin.
AB  - An ion-sensitive field effect transistor (ISFET)-based immunosensor was developed
      to detect/quantitate beta-Bungarotoxin (beta-BuTx), a potent presynaptic
      neurotoxin from the venom of Bungarus multicinctus. A murine monoclonal antibody
      (mAb 15) specific to beta-BuTx was immobilized onto silicon nitride wafers after
      silanization and activation with glutaraldehyde. A chip based enzyme linked
      immunosorbantassay (ELISA) was performed to ascertain antigen binding to the
      immobilized antibody. To develop an electrochemical immunosensing system for the
      detection/quantitation of beta-BuTx, an ISFET was used as a solid phase detector.
      MAb 15 was immobilized on the gate region of the ISFET. The antigen antibody
      reaction was monitored by the addition of urease conjugated rabbit anti-beta-BuTx
      antibodies. The sensor can detect toxin level as low as 15.6 ng/ml. The efficacy
      of the sensor for the determination of beta-BuTx from B. multicinctus venom was
      demonstrated in mouse model. Toxin concentration was highest at the site of
      injection (748.0+/-26 ng/ml) and moderate amount was found in the plasma (158.5+/
      13 ng/ml).

PMID- 12191932
TI  - A label-free optical technique for detecting small molecule interactions.
AB  - A novel approach for the label-free detection of molecular interactions is
      presented in which a colorimetric resonant grating is used as a surface binding
      platform. The grating, when illuminated with white light, is designed to reflect
      only a single wavelength. When molecules are attached to the surface, the
      reflected wavelength (color) is shifted due to the change of the optical path of
      light that is coupled into the grating. By linking receptor molecules to the
      grating surface, complementary binding molecules can be detected without the use
      of any kind of fluorescent probe or radioactive label. The detection technique is
      capable of detecting the addition and removal of small molecules as they interact
      with receptor molecules on the sensor surface or enzymes in the solution
      surrounding the sensor. Two assays are presented to exemplify the detection of
      small molecule interactions with the biosensor. First, an avidin receptor layer
      is used to detect 244 Da biotin binding. Second, a protease assay is performed in
      which a 136 Da p-nitroanilide (pNA) moeity is cleaved from an immobilized
      substrate. Because the sensor structure can be embedded in the plastic surfaces
      of microtiter plates or the glass surfaces of microarray slides, it is expected
      that this technology will be most useful in applications where large numbers of
      biomolecular interactions are measured in parallel, particularly when molecular
      labels will alter or inhibit the functionality of the molecules under study.
      Screening of pharmaceutical compound libraries with protein targets, and
      microarray screening of protein-protein interactions for proteomics are examples
      of applications that require the sensitivity and throughput afforded by this
      approach.

PMID- 12191933
TI  - On timing relations between brain and world.

PMID- 12191934
TI  - On subjective back-referral and how long it takes to become conscious of a
      stimulus: a reinterpretation of Libet's data.
AB  - The original data reported by Benjamin Libet and colleagues are reinterpreted,
      taking into account the facilitation which is experimentally demonstrated in the
      first of their series of articles. It is shown that the original data equally
      well or better support a quite different set of conclusions from those drawn by
      Libet. The new conclusions are that it takes only 80 ms (rather than 500 ms) for
      stimuli to come to consciousness and that "subjective back-referral of sensations
      in time" to the time of the stimulus does not occur (contrary to Libet's original
      interpretation of his results).

PMID- 12191935
TI  - Cortical movement preparation before and after a conscious decision to move.
AB  - The idea that our conscious decisions determine our actions has been challenged
      by a report suggesting that the brain starts to prepare for a movement before the
      person concerned has consciously decided to move (Libet, Gleason, Wright, &
      Pearl, 1983). Libet et al. claimed that their results show that our actions are
      not consciously initiated. The current article describes two experiments in which
      we attempted to replicate Libet et al.'s comparison of participants' movement
      related brain activity with the reported times of their decisions to move and
      also the reported times of their decisions of which hand to move. We also looked
      at the distribution of participants' reports over time to evaluate an alternative
      explanation of Libet et al.'s (1983) results. Although the Readiness Potential
      was usually present before all of the decisions to move, consistent with the
      findings of Keller and Heckhausen (1990) and Libet et al. (1983), we found that
      many reported decision times were before the onset of the Lateralized Readiness
      Potential, which measures hand-specific movement preparation. The latter finding
      is consistent with the conclusion that the LRP always started after the conscious
      decision to move. We conclude that even though activity related to movement
      anticipation may be present before a conscious decision to move, the cortical
      preparation necessary for the movement to happen immediately may not start until
      after the conscious decision to move.

PMID- 12191936
TI  - Problems in the timing of conscious experience.
AB  - Libet's (2000) arguments in defense of his interpretation of his experimental
      results are insufficient. The claims of my critical review (Gomes, 1998) do not
      suffer with his new statements.

PMID- 12191938
TI  - The timing of conscious states.

PMID- 12191937
TI  - Libet's temporal anomalies: a reassessment of the data.
AB  - Benjamin Libet compared the perceived time of direct brain stimulation to the
      perceived time of skin stimulation. His results are among the most controversial
      experiments at the interface between psychology and philosophy. The new element
      that I bring to this discussion is a reanalysis of Libet's raw data. Libet's
      original data were difficult to interpret because of the manner in which they
      were presented in tables. Plotting the data as psychometric functions shows that
      the observers have great uncertainty about the relative timing of events, as seen
      the shallow psychometric slopes. A second indication of uncertainty comes from
      Libet's use of three response categories, A first; B first; and A and B
      simultaneous. The large number of "perceptually simultaneous" responses provides
      a further measure of the difficulty of the judgment. There are thus a very broad
      range of stimulus delays in which the subject is unable to make an accurate
      ordering response. These points provide evidence that there is no compelling
      reason to invent exotic or ad hoc mechanisms to account for Libet's data since
      the uncertainty window is large enough to allow simple mechanism such as memory
      shifts. Libet argued that his data provide evidence for a backward referral in
      time. I argue that even though Libet's own data are weak, there are good
      arguments for a backward referral mechanism to help the subject make sense out of
      the tangled chaos of asynchronous information associated with experienced events.

PMID- 12191939
TI  - The interpretation of Libet's results on the timing of conscious events: a
      commentary.
AB  - A commentary on articles by Klein, Pockett, and Trevena and Miller, in this
      issue, is given. Average shift in the point of subjective equality (PSE),
      calculated by Klein on Libet's data, and corresponding change in mean shift,
      calculated by Libet et al. (1983), may be "corrected," taking as a reference
      point the end of the minimum train duration. Values obtained, if significant,
      indicate a latency for conscious sensation of the skin stimulus of at least 230
      ms. Pockett's main conclusions are favored, but her explanation of peripheral
      lemniscal couplings is found to be unconvincing. Trevena and Miller's article
      unsuccessfully tries to rescue a dualist interactionist view. Libet's method of
      timing intentions is thoroughly criticized.

PMID- 12191940
TI  - When timing the mind one should also mind the timing: biases in the measurement
      of voluntary actions.
AB  - Trevena and Miller (2002, this issue) provide further evidence that readiness
      potentials occur in the brain prior to the time that participants claim to have
      initiated a voluntary movement, a contention originally forwarded by Libet,
      Gleason, Wright, and Pearl (1983). In their examination of this issue, though,
      aspects of their data lead them to question whether their measurement of the
      initiation of a voluntary movement was accurate. The current article addresses
      this concern by providing a direct analysis of biases in this task. This was done
      by asking participants to make subjective timing decisions regarding a stimulus
      that could be measured objectively. Our findings suggest that their timing task
      was indeed biased such that participants' tend to report events as happening
      approximately 70 ms later than they actually happened. Implications for the
      original Libet et al. claims are discussed.

PMID- 12191941
TI  - Physical, neural, and mental timing.
AB  - The conclusions drawn by Benjamin Libet from his work with colleagues on the
      timing of somatosensorial conscious experiences has met with a lot of praise and
      criticism. In this issue we find three examples of the latter. Here I attempt to
      place the divide between the two opponent camps in a broader perspective by
      analyzing the question of the relation between physical timing, neural timing,
      and experiential (mental) timing. The nervous system does a sophisticated job of
      recombining and recoding messages from the sensorial surfaces and if these
      processes are slighted in a theory, it might become necessary to postulate weird
      operations, including subjective back-referral. Neuroscientifically inspired
      theories are of necessity still based on guesses, extrapolations, and
      philosophically dubious manners of speech. They often assume some neural
      correlate of consciousness (NCC) as a part of the nervous system that transforms
      neural activity in reportable experiences. The majority of neuroscientists appear
      to assume that the NCC can compare and bind activity patterns only if they arrive
      simultaneously at the NCC. This leads to a search for synchrony or to theories in
      terms of the compensation of differences in neural delays (latencies). This is
      the main dimension of the Libet discussion. Examples from vision research, such
      as "temporal-binding-by-synchrony" and the "flash-lag" effect, are then used to
      illustrate these reasoning patterns in more detail. Alternatively one could
      assume symbolic representations of time and space (symbolic "tags") that are not
      coded in their own dimension (not time in time and space in space). Unless such
      tags are multiplexed with the quality message (tickle, color, or motion), one
      gets a binding problem for tags. One of the hidden aspects of the discussion
      between Libet and opponents appears to be the following. Is the NCC smarter than
      the rest of the nervous system, so that it can solve the problems of local sign
      (e.g., "where is the event"?) and timing (e.g., "when did it occur?" and "how
      long did it last?") on its own, or are these pieces of information coded
      symbolically early on in the system? A supersmart NCC appears to be the
      assumption of Libet's camp (which includes Descartes, but also mystics). The wish
      to distribute the smartness evenly across all stages of processing in the nervous
      system (smart recodings) appears to motivate the opponents. I argue that there
      are reasons to side with the latter group.

PMID- 12191942
TI  - Two asymmetries governing neural and mental timing.
AB  - Mental timing studies may be influenced by powerful cognitive illusions that can
      produce an asymmetry in their rate of progress relative to neuronal timing
      studies. Both types of timing research are also governed by a temporal asymmetry,
      expressed by the fact that the direction of causation must follow time's arrow.
      Here we refresh our earlier suggestion that the temporal asymmetry offers promise
      as a means of timing mental activities. We update our earlier analysis of Libet's
      data within this framework. Then we consider the surprises which often occur on
      those rare occasions when neural timing experiments parallel mental timing work
      exactly. Together, these surprises and asymmetries prescribe a relentlessly
      meticulous and fully transparent exposition of timing methods, terms, and
      concepts which shuns plausible narratives, even when buttressed by rigorous
      formal models, unless guided by opposite empirical evidence.

PMID- 12191943
TI  - Libet's research on the timing of conscious intention to act: a commentary.
AB  - S. Pockett (Consciousness and Cognition, this issue) and G. Gomes (Consciousness
      and Cognition, this issue) discuss a possible bias in the method by which Libet's
      subjects estimated the time at which they became aware of their intent to move
      their hands. The bias, caused by sensory delay processing the clock information,
      would be sufficient to alter Trevena and Miller's (Consciousness and Cognition,
      this issue) conclusions regarding the timing of the lateralized readiness
      potential. I show that the flash-lag effect would compensate for that bias. In
      the last part of my commentary I note that the other target articles do not
      examine the most interesting aspect of Libet's unfashionable views on free will.
      I point out that Libet's views are less strange than they at first appear to be.

PMID- 12191944
TI  - In support of Pockett's critique of Libet's studies of the time course of
      consciousness.
AB  - Susan Pockett presents sound arguments supporting her reinterpretations of data
      that Libet and co-workers used to support a number of intriguing and influential
      conclusions regarding the microgenesis and timing of (a) conscious sensory
      experience and (b) volitionally controlled motor responses. The following
      analysis, extending and elaborating some of her main arguments, proposes that
      Libet's experimental methodologies and rationales, and thus also his
      interpretation of data, are flawed and that neglect or ignorance of
      methodological and empirical constraints well known to sensory psychologists
      risks drawing premature or faulty conclusions about the timing of conscious
      experience.

PMID- 12191945
TI  - The time of consciousness and vice versa.
AB  - The temporal granularity of consciousness may be far less fine than the real-time
      information processing mechanisms that underlie our sensitivity to small temporal
      differences. It is suggested that conscious time perception, like space
      perception, is subject to errors that belie a unitary underlying representation.
      E. R. Clay's (The Alternative: A Study in Psychology, 1882) concept of the
      "specious present," an extended moment represented in consciousness, is suggested
      as an alternative to the more common notion of instantaneous experience that
      underlies much reasoning based on the "time of arrival" in consciousness.

PMID- 12191946
TI  - The timing of mental events: Libet's experimental findings and their
      implications.
AB  - The major findings by Libet et al. are briefly summarized. The criticisms and
      alternative proposals by Trevena and Miller, Pockett, and Gomes (this issue) are
      analyzed and found to be largely unwarranted.

PMID- 12191947
TI  - Real latencies and facilitation.

PMID- 12191952
TI  - A neural correlate of consciousness related to repression.
AB  - In previous research Libet (1966) discovered that a critical time period for
      neural activation is necessary in order for a stimulus to become conscious. This
      necessary time period varies from subject to subject. In this current study, six
      subjects for whom the time for neural activation of consciousness had been
      previously determined were administered a battery of psychological tests on the
      basis of which ratings were made of degree of repressiveness. As hypothesized,
      repressive subjects had a longer critical time period for neural activation of
      consciousness, suggesting the possibility that this neurophysiological time
      factor is a necessary condition for the development of repression.

PMID- 12191953
TI  - Commentary on Shevrin, Ghannam, and Libet, "A Neural Correlate of Consciousness
      Related to Repression".

PMID- 12191955
TI  - Using illusory line motion to differentiate misrepresentation (Stalinesque) and
      misremembering (Orwellian) accounts of consciousness.
AB  - It has been suggested that the difference between misremembering (Orwellian) and
      misrepresentation (Stalinesque) models of consciousness cannot be differentiated
      (Dennett, 1991). According to an Orwellian account a briefly presented stimulus
      is seen and then forgotten, whereas by a Stalinesque account it is never seen. At
      the same time, Dennett suggested a method for assessing whether an individual is
      conscious of something. An experiment was conducted which used the suggested
      method for assessing consciousness to look at Stalinesque and Orwellian
      distinctions. A visual illusion, illusory line motion, was presented and
      participants were requested to make judgments that reflected what they were aware
      of. The participants were able to make responses indicating that they were aware
      of the actual stimulus in some conditions, but only of the illusion in others.
      This finding supports a claim that the difference between the Orwellian and
      Stalinesque accounts may be empirically observable and that both types of events
      may occur depending on task and stimulus parameters.

PMID- 12191956
TI  - An ostrich on a rock: commentary on Christie and Barresi (2002).
AB  - There are problems with both the theoretical logic and the interpretation of data
      in Christie and Barresi's (2002) interesting article. The general pattern of
      results (described as Orwellian) is easily incorporated into an information
      processing framework compatible with Dennett's analysis. In particular, different
      aspects of the illusory motion event are queried at different times and these
      aspects (line extent and manner of appearance) are not in conflict, so no
      revision of conscious content is necessary. Second, too much interpretive weight
      is placed on an anomalous pair of data points (described as Stalinesque) that do
      not seem fully interpretable within the author's framework and are probably
      susceptible to one of several alternative interpretations proposed here, though
      further investigation is necessary.

PMID- 12191958
TI  - Molecular dissection of craniofacial development using zebrafish.
AB  - The zebrafish, Danio rerio, is a small, freshwater teleost that only began to be
      used as a vertebrate genetic model by the late George Streisinger in the early
      1980s. The strengths of the zebrafish complement genetic studies in mice and
      embryological studies in avians. Its advantages include high fecundity,
      externally fertilized eggs and transparent embryos that can be easily
      manipulated, inexpensive maintenance, and the fact that large-scale mutagenesis
      screens can be performed. Here we review studies that have used the zebrafish as
      a model for craniofacial development. Lineage studies in zebrafish have defined
      the origins of the cranial skeleton at the single-cell level and followed the
      morphogenetic behaviors of these cells in skeletal condensations. Furthermore,
      genes identified by random mutational screening have now revealed genetic
      pathways controlling patterning of the jaw and other pharyngeal arches, as well
      as the midline of the skull, that are conserved between fish and humans. We
      discuss the potential impact of specialized mutagenesis screens and the future
      applications of this versatile, vertebrate developmental model system in the
      molecular dissection of craniofacial development.

PMID- 12191959
TI  - Cellular, molecular, and genetic determinants of tooth eruption.
AB  - Tooth eruption is a complex and tightly regulated process that involves cells of
      the tooth organ and the surrounding alveolus. Mononuclear cells (osteoclast
      precursors) must be recruited into the dental follicle prior to the onset of
      eruption. These cells, in turn, fuse to form osteoclasts that resorb alveolar
      bone, forming an eruption pathway for the tooth to exit its bony crypt. Some of
      the molecules possibly involved in the signaling cascades of eruption have been
      proposed in studies from null mice, osteopetrotic rodents, injections of putative
      eruption molecules, and cultured dental follicle cells. In particular,
      recruitment of the mononuclear cells to the follicle may require colony
      stimulating factor-one (CSF-1) and/or monocyte chemotactic protein-1 (MCP-1).
      Osteoclastogenesis is needed for the bone resorption and may involve inhibition
      of osteoprotegerin transcription and synthesis in the follicle, as well as
      enhancement of receptor activator of NF kappa B ligand (RANKL), in the adjacent
      alveolar bone and/or in the follicle. Paracrine signaling by parathyroid-hormone
      related protein and interleukin -1 alpha, produced in the stellate reticulum
      adjacent to the follicle, may also play a role in regulating eruption.
      Osteoblasts might also influence the process of eruption, the most important
      physiologic role likely being at the eruptive site, in the formation of
      osteoclasts through signaling via the RANKL/OPG pathway. Evidence thus far
      supports a role for an osteoblast-specific transcription factor, Cbfa1 (Runx2),
      in molecular events that regulate tooth eruption. Cbfa1 is also expressed at high
      levels by the dental follicle cells. This review concludes with a discussion of
      the several human conditions that result in a failure of or delay in tooth
      eruption.

PMID- 12191960
TI  - Dental caries vaccines: prospects and concerns.
AB  - Dental caries remains one of the most common infectious diseases of mankind.
      Cariogenic micro-organisms enter the dental biofilm early in life and can
      subsequently emerge, under favorable environmental conditions, to cause disease.
      In oral fluids, adaptive host defenses aroused by these infections are expressed
      in the saliva and gingival crevicular fluid. This review will focus on methods by
      which mucosal host defenses can be induced by immunization to interfere with
      dental caries caused by mutans streptococci. The natural history of mutans
      streptococcal colonization is described in the context of the ontogeny of mucosal
      immunity to these and other indigenous oral streptococci. Molecular targets for
      dental caries vaccines are explored for their effectiveness in intact protein and
      subunit (synthetic peptide, recombinant and conjugate) vaccines in pre-clinical
      studies. Recent progress in the development of mucosal adjuvants and viable and
      non-viable delivery systems for dental caries vaccines is described. Finally, the
      results of clinical trials are reviewed, followed by a discussion of the
      prospects and concerns of human application of the principles presented.

PMID- 12191961
TI  - The pathogenesis of oral lichen planus.
AB  - Both antigen-specific and non-specific mechanisms may be involved in the
      pathogenesis of oral lichen planus (OLP). Antigen-specific mechanisms in OLP
      include antigen presentation by basal keratinocytes and antigen-specific
      keratinocyte killing by CD8(+) cytotoxic T-cells. Non-specific mechanisms include
      mast cell degranulation and matrix metalloproteinase (MMP) activation in OLP
      lesions. These mechanisms may combine to cause T-cell accumulation in the
      superficial lamina propria, basement membrane disruption, intra-epithelial T-cell
      migration, and keratinocyte apoptosis in OLP. OLP chronicity may be due, in part,
      to deficient antigen-specific TGF-beta1-mediated immunosuppression. The normal
      oral mucosa may be an immune privileged site (similar to the eye, testis, and
      placenta), and breakdown of immune privilege could result in OLP and possibly
      other autoimmune oral mucosal diseases. Recent findings in mucocutaneous graft
      versus-host disease, a clinical and histological correlate of lichen planus,
      suggest the involvement of TNF-alpha, CD40, Fas, MMPs, and mast cell
      degranulation in disease pathogenesis. Potential roles for oral Langerhans cells
      and the regional lymphatics in OLP lesion formation and chronicity are discussed.
      Carcinogenesis in OLP may be regulated by the integrated signal from various
      tumor inhibitors (TGF-beta 1, TNF-alpha, IFN-gamma, IL-12) and promoters (MIF,
      MMP-9). We present our recent data implicating antigen-specific and non-specific
      mechanisms in the pathogenesis of OLP and propose a unifying hypothesis
      suggesting that both may be involved in lesion development. The initial event in
      OLP lesion formation and the factors that determine OLP susceptibility are
      unknown.

PMID- 12191962
TI  - Dynamics of the human masticatory system.
AB  - In this review, the movement characteristics of the human masticatory system are
      discussed from a biomechanical perspective. The discussion is based upon the
      three fundamental laws of mechanics applied to the various anatomical structures
      that are part of the masticatory system. An analysis of the forces and torques
      applied to the mandible by muscles, joints, articular capsules, and teeth is used
      to assess the determinants of jaw movement. The principle of relating the
      interplay of forces to the center of gravity of the lower jaw, in contrast to a
      hinge axis near its joints, is introduced. It is evident that the muscles are the
      dominant determinants of jaw movement. The contributions of the individual
      muscles to jaw movements can be derived from the orientation of their lines of
      action with respect to the center of gravity of the lower jaw. They cause the jaw
      to accelerate with six degrees of freedom. The ratio between linear and angular
      accelerations is subtly dependent on the mass and moments of inertia of the jaw,
      and the structures that are more or less rigidly attached to it. The effects of
      articular forces must be taken into account, especially if the joints are loaded
      asymmetrically. The muscles not only move the jaw but also maintain articular
      stability during midline movements. Passive structures, such as the ligaments,
      become dominant only when the jaw reaches its movement boundaries. These
      ligaments are assumed to prevent joint dislocation during non-midline movements.

PMID- 12191963
TI  - Regulation of the proximal tubular sodium/proton exchanger NHE3 in rats with
      puromycin aminonucleoside (PAN)-induced nephrotic syndrome.
AB  - Excessive proteinuria due to loss of glomerular permselectivity in nephrotic
      syndrome can cause disturbances in renal salt and water handling with edema
      formation. Apart from oncotic and hydrostatic mechanisms associated with
      hypoalbuminemia, primary derangements in renal tubular sodium transport may
      contribute to the pathogenesis of nephrotic edema. Whereas there is evidence for
      an increase of cortical collecting duct sodium reabsorption in nephrotic rats, it
      remains controversial whether proximal tubule sodium transport may also be
      activated in this condition. The regulation of the cortical Na/H exchanger NHE3,
      the main pathway for Na reabsorption in the proximal tubule (PT), was
      investigated in rats with puromycin aminonucleoside (PAN)-induced nephrotic
      syndrome. PAN rats developed reduced GFR, severe proteinuria, and sodium
      retention within 3 d. After 10 d, immunoblots of brush border vesicles revealed a
      decreased abundance of NHE3 in nephrotic animals. However, the Na/H antiporter
      activity in the same vesicle preparations was not significantly altered.
      Antiporter activity normalized for NHE3 protein was increased by 88% in nephrotic
      animals (P = 0.025). Immunohistochemistry with the same polyclonal antibody as
      for immunoblots revealed a decrease of NHE3 abundance in PT. In contrast,
      immunoreactivity for the monoclonal antibody 2B9, which specifically recognizes
      the non-megalin-associated, transport-competent pool of NHE3, was higher in PAN
      treated rats than in controls. In conclusion, increased sodium reabsorption might
      be associated with a shift of NHE3 from an inactive pool to an active pool, thus
      contributing to sodium retention in a state of proteinuria.

PMID- 12191964
TI  - Renal interstitial fluid angiotensin I and angiotensin II concentrations during
      local angiotensin-converting enzyme inhibition.
AB  - It was recently demonstrated that angiotensin II (AngII) concentrations in the
      renal interstitial fluid (RIF) of anesthetized rats were in the nanomolar range
      and were not reduced by intra-arterial infusion of an angiotensin-converting
      enzyme (ACE) inhibitor (enalaprilat). This study was performed to determine
      changes in RIF AngI and AngII concentrations during interstitial administration
      of ACE inhibitors (enalaprilat and perindoprilat). Studies were also performed to
      determine the effects of enalaprilat on the de novo formation of RIF AngII
      elicited by interstitial infusion of AngI. Microdialysis probes (cut-off point,
      30,000 D) were implanted in the renal cortex of anesthetized rats and were
      perfused at 2 micro l/min. The effluent dialysate concentrations of AngI and
      AngII were measured by RIA, and reported values were corrected for the
      equilibrium rates at this perfusion rate. Basal RIF AngI (0.74 +/- 0.05 nM) and
      AngII (3.30 +/- 0.17 nM) concentrations were much higher than plasma AngI and
      AngII concentrations (0.15 +/- 0.01 and 0.14 +/- 0.01 nM, respectively; n = 27).
      Interstitial infusion of enalaprilat through the microdialysis probe (1 or 10 mM
      in the perfusate; n = 5 and 8, respectively) significantly increased RIF AngI
      concentrations but did not significantly alter AngII concentrations. However,
      perindoprilat (10 mM in the perfusate, n = 7) significantly decreased RIF AngII
      concentrations by 22 +/- 4% and increased RIF AngI concentrations. Interstitial
      infusion of AngI (100 nM in the perfusate, n = 7) significantly increased the RIF
      AngII concentration to 8.26 +/- 0.75 nM, whereas plasma AngI and AngII levels
      were not affected (0.15 +/- 0.02 and 0.14 +/- 0.02 nM, respectively). Addition of
      enalaprilat to the perfusate (10 mM) prevented the conversion of exogenously
      added AngI. These results indicate that addition of AngI in the interstitial
      compartment leads to low but significant conversion to AngII via ACE activity
      (blocked by enalaprilat). However, the addition of ACE inhibitors directly into
      the renal interstitium, via the microdialysis probe, either did not reduce RIF
      AngII levels or reduced levels by a small fraction of the total basal level,
      suggesting that much of the RIF AngII is formed at sites not readily accessible
      to ACE inhibition or is formed via non-ACE-dependent pathways.

PMID- 12191965
TI  - Prognostic significance of renal function in elderly patients with isolated
      systolic hypertension: results from the Syst-Eur trial.
AB  - Several reports suggest that markers of renal function such as serum creatinine,
      serum uric acid, and urinary excretion of protein may be related to
      cardiovascular complications and mortality. This study analyzed the data from the
      Syst-Eur trial, which was a randomized, placebo-controlled, double-blind
      intervention trial in elderly patients with isolated systolic hypertension. The
      purpose was to evaluate whether serum levels of creatinine and uric acid and
      urinary protein excretion at entry are related to subsequent morbidity and
      mortality. Incidence rates of total mortality, cardiovascular mortality, stroke
      (fatal as well as nonfatal), coronary events, and all cardiovascular endpoints
      were calculated for each quintile of serum creatinine or serum uric acid or for
      each category of protein excretion (none, trace, and overt). Crude and adjusted
      relative hazard rates were also determined for each 20 micro M increase in serum
      creatinine, each 50 micro M increase in serum uric acid, and for each protein
      excretion category. Even when adjusted for age, gender, and various other
      covariates, serum creatinine was significantly associated with a worse prognosis.
      There was an U-shaped relationship between serum uric acid and total mortality,
      but otherwise no obvious relationships were detected between serum uric acid
      levels and complications when appropriate adjustments were made for confounding
      variables. Proteinuria at entry was a significant predictor of total mortality
      and all cardiovascular endpoints. It is concluded that higher levels of serum
      creatinine and trace or overt proteinuria are associated with an increased number
      of cardiovascular events and with a higher mortality in patients with isolated
      systolic hypertension.

PMID- 12191966
TI  - PPAR agonists amplify iNOS expression while inhibiting NF-kappaB: implications
      for mesangial cell activation by cytokines.
AB  - In acute inflammation, the transcription factor NF-kappaB is activated and
      increases the expression of multiple pro-inflammatory genes. Agonists of
      peroxisome proliferator activated receptors (PPAR) have been reported to exert
      antiinflammatory effects in various systems. In keeping with such an
      antiinflammatory role, it was found that several PPAR agonists, including
      Wy14,643, clofibrate, carbaprostacyclin, and ciglitazone inhibited NF-kappaB
      activity and increased IkappaBalpha levels in cytokine-stimulated mesangial cells
      (MC). Activation of NF-kappaB has been found to be crucial to the cytokine
      elicited expression of inducible nitric oxide synthase (iNOS). Despite the
      inhibitory effect of PPAR agonists on NF-kappaB activity, this study provides
      experimental data demonstrating that these agonists amplify cytokine-elicited NO
      generation in MC, potentiating iNOS protein expression approximately threefold.
      The upregulation of iNOS expression occurred at the mRNA level and apparently did
      not result from iNOS mRNA stabilization. Clofibrate and ciglitazone amplified the
      cytokine-elicited stimulation of a 16-Kb human iNOS promoter construct in stably
      transfected MC, suggesting that PPAR agonists potentiate iNOS induction through
      transcriptional mechanisms. MC express all three PPAR proteins. However, iNOS
      potentiation did not correlate with increased PPAR activity. In addition,
      Wy14,643-induced amplification of cytokine-elicited iNOS levels also occurred in
      RAW264.7 macrophages and in human epithelial Caco-2 and HT-29 cells. The
      observation that these epithelial cell lines express an inactive, truncated
      PPARalpha variant suggests that a classical PPARalpha agonist, such as Wy14,643,
      may act through PPARalpha-independent mechanisms. In conclusion, these results
      show that, despite reducing NF-kappaB activity, PPAR agonists may amplify the
      expression of certain NF-kappaB-dependent genes that are relevant to the
      inflammatory process, like iNOS.

PMID- 12191967
TI  - Neutrophil membrane expression of proteinase 3 (PR3) is related to relapse in PR3
      ANCA-associated vasculitis.
AB  - Wegener granulomatosis (WG) is strongly associated with the presence of
      antineutrophil cytoplasm autoantibodies (ANCA) with specificity for proteinase 3
      (PR3). Relapses of WG are frequently preceded by a rise of autoantibody titer and
      PR3-ANCA are able to activate primed neutrophils in vitro. Except being stored
      intracellularly and translocated to the cell surface upon neutrophil stimulation,
      PR3 can also be detected on the surface of non-stimulated neutrophils (membrane
      PR3 or mPR3), with an interindividual variability in percentages of mPR3(-)
      positive cells and level of mPR3 expression. This study began with the hypothesis
      that the presence of PR3 on the surface of non-stimulated neutrophils enables
      interaction with PR3-ANCA and influences clinical manifestations of the disease.
      It analyzed mPR3 expression on neutrophils of 89 WG patients in complete
      remission and 72 healthy controls to evaluate whether the presence of PR3 on the
      surface of resting neutrophils is related to clinical manifestations of WG and/or
      to the susceptibility to develop relapses. The number of patients with a bimodal
      mPR3 expression on resting neutrophils did not differ between patients and
      controls. However, in WG patients, an increased percentage of mPR3(+) neutrophils
      and an elevated level of mPR3 expression compared with healthy individuals (P =
      0.037) were found. Within the group of WG patients, an elevated level of mPR3
      expression was significantly associated with an increased risk for relapse (P =
      0.021) and with an increased relapse rate (P = 0.011), but not with the disease
      extent or particular manifestations at diagnosis or at relapse. These data
      support the hypothesis that PR3 expression on the membrane of neutrophils plays a
      role in the pathophysiology of PR3-ANCA associated vasculitis.

PMID- 12191968
TI  - Molecular basis for high renal cell sensitivity to the cytotoxic effects of
      shigatoxin-1: upregulation of globotriaosylceramide expression.
AB  - Cellular injury in post-diarrheal hemolytic-uremic syndrome (D+HUS) is related to
      shigatoxin (Stx) binding to globotriaosylceramide (Gb3). High renal Gb3
      expression may determine renal susceptibility in D+HUS; however, the molecular
      mechanism(s) responsible for such relatively abundant Gb3 levels are unknown.
      Consequently, kidney cells expressing high Gb3 (cultured human proximal tubule
      cells [HPT]) were compared with non-kidney cells with low Gb3 content (cultured
      human brain microvascular endothelial cells [HBEC]). HPT were much more sensitive
      to the cytotoxic and protein synthesis inhibitory effects of Stx-1; this
      correlated with Gb3 content and (125)I-Stx-1 binding. HPT had greater Gb3
      synthase (GalT6) and lower alpha-galactosidase activities than HBEC, whereas
      lactosylceramide synthase (GalT2) activity was higher in HBEC. Ceramide
      glucosyltransferase (CGT) activity was similar between the two cell types. The
      higher HPT GalT6 activity was associated with increased GalT6 mRNA steady-state
      levels, but no difference in GalT6 mRNA half-life. The lower HPT alpha
      galactosidase activity was associated with reduced alpha-galactosidase mRNA
      steady-state levels but no difference in alpha-galactosidase mRNA half-life.
      Higher HBEC GalT2 activity was associated with increased steady-state GalT2 mRNA
      levels. These studies suggest that high renal Gb3 expression is due to enhanced
      GalT6 gene transcription and reduced alpha-galactosidase gene transcription and
      occur despite relatively low GalT2 activity.

PMID- 12191969
TI  - Identification and characterization of Pkhd1, the mouse orthologue of the human
      ARPKD gene.
AB  - PKHD1, the gene mutated in human autosomal recessive polycystic kidney disease
      has recently been identified. Its translation products are predicted to belong to
      a superfamily of proteins involved in the regulation of cellular adhesion and
      repulsion. One notable aspect of the gene is its unusually complex pattern of
      splicing. This study shows that mouse Pkhd1 and its translation products have
      very similar properties to its human orthologue. Mouse Pkhd1 extends over
      approximately 500 kb of genomic DNA, includes a minimum of 68 nonoverlapping
      exons, and exhibits a complex pattern of splicing. The longest ORF encodes a
      protein of 4059aa predicted to have an N-terminal signal peptide, multiple IPTs
      and PbH1 repeats, a single transmembrane span (TM), and a short cytoplasmic C
      terminus. Although the protein sequence is generally well conserved
      (approximately 73% average identity), the C-termini share only 55% identity. The
      pattern of Pkhd1 expression by in situ hybridization was also examined in
      developing and adult mouse tissues over a range of ages (E12.5 to 3 mo
      postnatal). High levels of expression were present in renal and biliary tubular
      structures at all time points examined. Prominent Pkhd1 signals were also found
      in a number of other organs and tissues. Tissue-specific differences in
      transcript expression were revealed through the use of single exon probes. These
      data show that key features of human PKHD1 are highly conserved in the mouse and
      suggest that the complicated pattern of splicing is likely to be functionally
      important.

PMID- 12191970
TI  - Functional characterization of a calcium-sensing receptor mutation in severe
      autosomal dominant hypocalcemia with a Bartter-like syndrome.
AB  - The extracellular Ca(2+)-sensing receptor (CaSR) plays an essential role in
      extracellular Ca(2+) homeostasis by regulating the rate of parathyroid hormone
      (PTH) secretion and the rate of calcium reabsorption by the kidney. Activation of
      the renal CaSR is thought to inhibit paracellular divalent cation reabsorption in
      the cortical ascending limb (cTAL) both directly and indirectly via a decrease in
      NaCl transport. However, in patients with autosomal dominant hypocalcemia (ADH),
      caused by CaSR gain-of-function mutations, a defect in tubular NaCl reabsorption
      with renal loss of NaCl has not been described so far. This article describes a
      patient with ADH due to a gain-of-function mutation in the CaSR, L125P,
      associated with a Bartter-like syndrome that is characterized by a decrease in
      distal tubular fractional chloride reabsorption rate and negative NaCl balance
      with secondary hyperaldosteronism and hypokalemia. The kinetics of activation of
      the L125P mutant receptor expressed in HEK-293 cells, assessed by measuring CaSR
      stimulated changes in intracellular Ca(2+) and ERK activity, showed a dramatic
      reduction in the EC(50) for extracellular Ca(2+) compared with the wild-type and
      a loss-of-function mutant CaSR (I40F). This study describes the first case of ADH
      associated with a Bartter-like syndrome. It is herein proposed that the L125P
      mutation of the CaSR, which represents the most potent gain-of-function mutation
      reported so far, may reduce NaCl reabsorption in the cTAL sufficiently to result
      in renal loss of NaCl with secondary hyperaldosteronism and hypokalemia.

PMID- 12191971
TI  - Cell-biologic and functional analyses of five new Aquaporin-2 missense mutations
      that cause recessive nephrogenic diabetes insipidus.
AB  - Mutations in the Aquaporin-2 gene, which encodes a renal water channel, have been
      shown to cause autosomal nephrogenic diabetes insipidus (NDI), a disease in which
      the kidney is unable to concentrate urine in response to vasopressin. Most AQP2
      missense mutants in recessive NDI are retained in the endoplasmic reticulum (ER),
      but AQP2-T125M and AQP2-G175R were reported to be nonfunctional channels
      unimpaired in their routing to the plasma membrane. In five families, seven novel
      AQP2 gene mutations were identified and their cell-biologic basis for causing
      recessive NDI was analyzed. The patients in four families were homozygous for
      mutations, encoding AQP2-L28P, AQP2-A47V, AQP2-V71M, or AQP2-P185A. Expression in
      oocytes revealed that all these mutants, and also AQP2-T125M and AQP2-G175R,
      conferred a reduced water permeability compared with wt-AQP2, which was due to ER
      retardation. The patient in the fifth family had a G>A nucleotide substitution in
      the splice donor site of one allele that results in an out-of-frame protein. The
      other allele has a nucleotide deletion (c652delC) and a missense mutation
      (V194I). The routing and function of AQP2-V194I in oocytes was not different from
      wt-AQP2; it was therefore concluded that c652delC, which leads to an out-of-frame
      protein, is the NDI-causing mutation of the second allele. This study indicates
      that misfolding and ER retention is the main, and possibly only, cell-biologic
      basis for recessive NDI caused by missense AQP2 proteins. In addition, the
      reduced single channel water permeability of AQP2-A47V (40%) and AQP2-T125M (25%)
      might become of therapeutic value when chemical chaperones can be found that
      restore their routing to the plasma membrane.

PMID- 12191972
TI  - Evidence for the existence of two distinct functions for the inducible NO
      synthase in the rat kidney: effect of aminoguanidine in rats with 5/6 ablation.
AB  - The functional role of the NO synthase (NOS) isoforms in the normal or diseased
      kidney is uncertain. This study examined the renal expression of the endothelial
      (eNOS), neuronal (nNOS), and inducible (iNOS) isoforms by both
      immunohistochemistry and Western blot analyses in sham-operated rats (S) and in
      rats subjected to 5/6 nephrectomy (Nx). Primary antibodies from two different
      sources were used to detect iNOS. Additional S and Nx rats were chronically
      treated with aminoguanidine (AG), a selective iNOS inhibitor. All three isoforms
      were clearly expressed in S kidney. Their renal abundance, evaluated by Western
      blot analysis, fell in Nx rats. With the use of anti-iNOS antibodies from two
      distinct sources, the immunohistochemical analysis showed the presence of what
      appeared to be two distinct iNOS fractions: a "tubular" fraction, present in S
      and with decreased intensity in Nx; and an "interstitial" fraction, observed only
      in inflamed areas of Nx rats. AG treatment greatly attenuated renal injury in Nx
      rats by a direct antiinflammatory effect, likely related to iNOS inhibition,
      rather than to amelioration of renal hemodynamics or to reduced protein
      glycation. These observations suggest that: (1) the functional role of the renal
      iNOS isoform may vary dramatically under different physiologic conditions; (2)
      caution should be taken in the interpretation of immunohistochemical iNOS data,
      because antibodies from different sources may detect different iNOS fractions;
      and (3) AG treatment may become useful in the treatment of human progressive
      nephropathies, even those not associated with diabetes or aging.

PMID- 12191973
TI  - Postischemic acute renal failure is reduced by short-term statin treatment in a
      rat model.
AB  - Postischemic acute renal failure (ARF) is common and often fatal. Cellular
      mechanisms include cell adhesion, cell infiltration and generation of oxygen free
      radicals, and inflammatory cytokine production. Hydroxy-3-methylglutaryl coenzyme
      A reductase inhibitors ("statins") directly influence inflammatory mechanisms.
      The hypothesis that ischemia-induced ARF could be ameliorated with statin
      treatment was investigated and possible molecular mechanisms were analyzed in a
      uninephrectomized rat model. Male Sprague-Dawley rats were pretreated with
      cerivastatin (0.5 mg/kg) or vehicle for 3 d. Ischemic ARF was induced by left
      renal artery clipping for 45 min, while the right kidney was being removed. After
      24 h of ARF, serum creatinine levels were increased 7.5-fold in vehicle-treated
      control animals with ARF, compared with sham-operated animals (P < 0.005). Statin
      treatment reduced the creatinine level elevation by 40% (P < 0.005).
      Simultaneously, ischemia-induced severe decreases in GFR were significantly
      ameliorated by statin treatment (sham operation, 0.95 +/- 0.09 ml/min, n = 13;
      ischemia without treatment, 0.06 +/- 0.02 ml/min, n = 9; ischemia with statin
      pretreatment, 0.21 +/- 0.03 ml/min, n = 11; P < 0.001). Furthermore, statin
      pretreatment prevented the occurrence of tubular necrosis, with marked loss of
      the brush border, tubular epithelial cell detachment, and tubular obstruction in
      the S3 segment of the outer medullary stripe. In addition, monocyte and
      macrophage infiltration was almost completely prevented, intercellular adhesion
      molecule-1 upregulation was greatly decreased, and inducible nitric oxide
      synthase expression was reduced. Fibronectin and collagen IV expression was
      reduced, approaching levels observed in sham-operated animals. In vehicle-treated
      rats with ARF, mitogen-activated protein kinase extracellular activated kinase
      1/2 activity was increased and the transcription factors nuclear factor-kappaB
      and activator protein-1 were activated. Statin treatment reduced this activation
      toward levels observed in sham-operated rats. The data suggest that hydroxy-3
      methylglutaryl coenzyme A reductase inhibition protects renal tissue from the
      effects of ischemia-reperfusion injury and thus reduces the severity of ARF. The
      chain of events may involve anti-inflammatory effects, with inhibition of mitogen
      activated protein kinase activation and the redox-sensitive transcription factors
      nuclear factor-kappaB and activator protein-1.

PMID- 12191974
TI  - The effects of sevelamer hydrochloride and calcium carbonate on kidney
      calcification in uremic rats.
AB  - The control of serum phosphorus (P) and calcium-phosphate (Ca x P) product is
      critical to the prevention of ectopic calcification in chronic renal failure
      (CRF). Whereas calcium (Ca) salts, the most commonly used phosphate binders,
      markedly increase serum Ca and positive Ca balance, the new calcium- and aluminum
      free phosphate binder, sevelamer hydrochloride (RenaGel), reduces serum P without
      altering serum Ca in hemodialysis patients. Using an experimental model of CRF,
      these studies compare sevelamer and calcium carbonate (CaCO(3)) in the control of
      serum P, secondary hyperparathyroidism (SH), and ectopic calcifications. 5/6
      nephrectomized rats underwent one of the following treatments for 3 mo: uremic +
      high-P diet (U-HP); UHP + 3% CaCO(3) (U-HP+C); UHP + 3% sevelamer (U-HP+S).
      Sevelamer treatment controlled serum P independent of increases in serum Ca, thus
      reducing serum Ca x P product and further deterioration of renal function, as
      indicated by the highest creatinine clearances. Sevelamer was as effective as
      CaCO(3) in the control of high-P-induced SH, as shown by similar serum PTH
      levels, parathyroid (PT) gland weight, and markers of PT hyperplasia. Also, both
      P binders elicited similar efficacy in reducing the myocardial and hepatic
      calcifications induced by uremia. However, sevelamer caused a dramatic reduction
      of renal Ca deposition (29.8 +/- 8.6 micro g/g wet tissue) compared with both U
      HP (175.5 +/- 45.7 micro g/g wet tissue, P < 0.01) and the U-HP+C (58.9 +/- 13.7
      micro g/g wet tissue, P < 0.04). Histochemical analyses using Von Kossa and
      Alizarin red S staining of kidney sections confirmed these findings. The high
      number of foci of calcification in the kidney of uremic controls (108 +/- 25) was
      reduced to 33.0 +/- 11.3 by CaCO(3) and decreased even further with sevelamer
      (16.4 +/- 8.9, P < 0.02 versus CaCO(3)). Importantly, the degree of
      tubulointerstitial fibrosis was also markedly lower in U-HP+S (5%) compared with
      either U-HP+C (30%) or U-HP (50%). It is concluded that in experimental CRF in
      rats, despite a similar control of serum P and SH, sevelamer is more effective
      than CaCO(3) in preventing renal Ca deposition and tubulointerstitial fibrosis,
      including better preservation of renal function. These findings cannot be
      extrapolated to human disease, and further studies in patients are necessary to
      determine the benefits of either P binder.

PMID- 12191975
TI  - Characteristics of polymeric lambda-IgA binding to leukocytes in IgA nephropathy.
AB  - IgA nephropathy (IgAN) is characterized by predominant mesangial polymeric IgA1
      (pIgA1) deposits, with increased plasma IgA1 levels. Plasma IgA levels are
      determined by the rate of IgA production, uptake by leukocytes, and removal by
      hepatocytes. Fc(alpha) receptor 1 (Fc(alpha)R1) is a candidate molecule for the
      regulation of IgA levels, but reports of its expression in leukocytes in IgAN are
      conflicting. Increased binding of endogenous IgA to circulating granulocytes and
      monocytes in IgAN was demonstrated in this study. Fc(alpha)R1 expression on
      leukocytes was increased, independently of plasma IgA levels. Fc(alpha)R1 was not
      saturated in leukocytes, because of internalization of IgA after uptake. Further
      binding of exogenous IgA isolated from individual subjects was observed with
      leukocytes from the same subjects. Compared with cells from control subjects,
      granulocytes but not monocytes from patients with IgAN exhibited a greater
      binding capacity for exogenous IgA, predominantly pIgA. To circumvent the
      possibility that endogenous IgA might alter Fc(alpha)R1 expression, granulocytes
      or monocytes derived from the HL-60 or U937 cell lines were used to explore the
      nature of IgA binding. A higher affinity for pIgA was demonstrated. Inhibition
      studies using unlabeled IgA, other serum proteins, or a specific Fc(alpha)R1
      blocking antibody suggested binding mechanisms other than Fc(alpha)R1 for pIgA
      uptake by leukocytes. This study also suggested the migration and/or
      sequestration of "activated" leukocytes with predominant lambda-IgA in the
      mononuclear phagocytic system or inflammatory tissues, after the initial binding
      of lambda-pIgA. These immunologic abnormalities might contribute to the
      glomerulointerstitial injury in IgAN, in the presence of leukocytic infiltration.

PMID- 12191976
TI  - Molecular identification of SV40 infection in human subjects and possible
      association with kidney disease.
AB  - Simian virus 40 (SV40), a monkey polyomavirus that is believed to have entered
      the human population through contaminated vaccines, is known to be renotropic in
      simians. If indeed SV40 is endemic within the human population, the route of
      transmission is unknown. It was therefore hypothesized that SV40 might be
      renotropic in humans and be detected more frequently in samples obtained from
      patients with kidney diseases. This study found that typical polyomavirus
      cytopathic effects (CPE) were present and SV40 T antigen was detected in CV-1
      cells cultured with peripheral blood mononuclear cells (PBMC) or urinary cells
      obtained from patients with kidney disease and healthy volunteers. DNA sequences
      homologous to the SV40 viral regulatory genome were detected by PCR in urinary
      cells from 15 (41%) of 36 patients with focal segmental glomerulosclerosis
      (FSGS), 2 (10%) of 20 patients with other kidney diseases, and 1 (4%) of 22
      healthy volunteers (FSGS compared with other glomerular disease, P < 0.02; FSGS
      compared with healthy volunteers, P = 0.003). SV40 viral regulatory region genome
      was detected from PBMC at similar frequencies in patients with FSGS (35%), other
      glomerular diseases (20%), and healthy volunteers (22%). SV40 genome was detected
      by PCR in kidney tissues from 17 (56%) of 30 of patients with FSGS and 4 (20%) of
      20 patients with minimal change disease and membranous nephropathy (P < 0.01).
      Considerable genetic heterogeneity of the viral regulatory region was detected,
      which argues against laboratory contamination. SV40 genome was localized to renal
      tubular epithelial cell nuclei in renal biopsies of patients with FSGS by in situ
      hybridization. This study demonstrates for the first time that human kidney can
      serve as a reservoir for SV40 replication and that SV40 may contribute to the
      pathogenesis of kidney disease, particularly FSGS.

PMID- 12191977
TI  - Low-intensity warfarin is ineffective for the prevention of PTFE graft failure in
      patients on hemodialysis: a randomized controlled trial.
AB  - Polytetrafluoroethylene (PTFE) dialysis grafts in patients with end-stage renal
      disease (ESRD) are prone to thrombotic failure. The objective of this
      multicenter, randomized, double-blind, placebo-controlled clinical trial was to
      determine if warfarin reduces the risk of failure of PTFE dialysis grafts.
      Patients with ESRD and newly placed PTFE grafts were studied at community and
      academic dialysis centers in Southwestern Ontario. Patients were allocated to
      receive warfarin or matching placebo, with the warfarin administered to achieve a
      target INR of 1.4 to 1.9. Time to graft failure was the main outcome measure. A
      total of 107 patients (56 allocated to warfarin) were randomized. The time-to
      event analysis revealed no significant difference in the likelihood of graft
      survival between the two groups (odds ratio, 1.76 in favor of placebo; 95%
      confidence interval, 0.72 to 4.34). Six major bleeds occurred in five patients
      allocated to warfarin compared with none in the patients who received placebo (P
      = 0.03). In conclusion, low-dose warfarin was associated with an excess of
      clinically important major bleeding in patients with ESRD enrolled in this study.
      Furthermore, low-intensity, monitored-dose warfarin does not appear to prolong
      PTFE graft survival.

PMID- 12191978
TI  - Measuring the efficacy of a quality improvement program in dialysis adequacy with
      changes in center effects.
AB  - End-stage renal disease (ESRD) patients treated with hemodialysis have a high
      mortality rate, which is largely due to inadequate dialysis. Dialysis adequacy,
      measured by the urea reduction ratio (URR), tends to be correlated within
      dialysis facilities with wide variations in average center adequacy. These are
      characteristics of a center effect, which can have an important impact on
      dialysis adequacy. This study measured the center effect observed in an ESRD
      Network before and after a successful quality improvement project (QIP). URR
      values were recorded on patients sampled from 196 facilities in ESRD Network 6
      before (pre-QIP, n = 5309) and after (post-QIP, n = 5753). These data was used to
      determine the within center correlation (rho) of individual URR values and
      between center variation in aggregate URR values in both samples. The overall
      mean URR improved from the pre- to post-QIP sample (mean URR 64.7 +/- 0.1 versus
      69.8 +/- 0.1, respectively; P = 0.001). There was a high degree of within center
      correlation in dialysis adequacy across the facilities, which significantly
      diminished post-QIP (rho, 0.15 [95% CI, 0.12 to 0.18] versus rho, 0.06 [95% CI,
      0.04 to 0.08]). The between center variation in mean URR also declined from the
      pre-QIP to the post-QIP sample (SD, 3.6 versus 2.8). In conclusion, there is a
      center effect on dialysis adequacy measurable in an ESRD Network, which
      diminishes after a successful QIP; therefore, when implementing a QIP to improve
      dialysis adequacy, changes in the center effect should be considered a potential
      indicator of the efficacy of the intervention.

PMID- 12191979
TI  - Seasonal variations in clinical and laboratory variables among chronic
      hemodialysis patients.
AB  - Seasonal variations in BP among chronic hemodialysis patients have been reported.
      It was hypothesized that other characteristics of these patients might also vary
      with the seasons. Twenty-one clinical and laboratory variables were examined for
      seasonal variations among 1445 patients enrolled in the Hemodialysis Study,
      sponsored by the National Institute of Diabetes and Digestive and Kidney
      Diseases. Mixed-effects models were applied to longitudinal changes (up to 45 mo)
      for individual patients for 19 of the 21 variables, which were measured at least
      twice each year, to determine the seasonal component of each variable. Seasonal
      variations in the other two variables, i.e., protein and energy intakes
      determined from annual dietary records, were assessed in cross-sectional
      comparisons of intakes of patients entering the study at different time points.
      Thirteen of the 21 variables examined demonstrated statistically significant (P <
      0.01) seasonal components in their longitudinal variations. Predialysis blood
      urea nitrogen concentrations peaked in March, which coincided approximately with
      the peak protein catabolic rates, as well as protein and energy intakes
      (determined by dietary recall). Predialysis systolic and diastolic BP values were
      highest in winter and lowest in summer, corroborating previous reports. In
      addition, the lower predialysis BP values in summer were associated with higher
      outdoor temperatures and less interdialytic fluid gain. The mean predialysis
      hematocrit values were highest in July, which could not be attributed solely to
      the estimated changes in plasma volume. Seasonal variations in clinical and
      laboratory variables occur commonly among chronic hemodialysis patients. The
      reasons for most of these variations are not apparent and require further
      investigation. Nonetheless, failure to consider these variations might lead to
      biases in the interpretation of clinical studies. In addition, awareness of these
      variations might facilitate the interpretation of laboratory results and the
      clinical treatment of these patients.

PMID- 12191980
TI  - Comparing mortality of elderly patients on hemodialysis versus peritoneal
      dialysis: a propensity score approach.
AB  - The objective of this study was to evaluate differences in mortality over the
      first year of renal replacement therapy (RRT) between elderly patients starting
      treatment on hemodialysis (HD) versus peritoneal dialysis (PD). For the period of
      1991 to mid-1996, this study defined an inception cohort of all patients aged >65
      yr with new-onset chronic RRT who were New Jersey Medicare and/or Medicaid
      beneficiaries in the year before RRT and who had been diagnosed with renal
      disease more than 1 yr before RRT. Propensity scores were calculated for first
      treatment assignment from a large number of baseline covariates. Mortality was
      then compared among patients initially assigned to HD versus PD using
      multivariate 90-d interval Cox models controlled for propensity scores and center
      stratification. Peritoneal dialysis starters had a 16% higher rate of death
      during the first 90 d of RRT compared with HD patients (hazard ratio [HR], 1.16;
      95% confidence interval [CI], 0.96 to 1.42)]. Mortality did not differ between
      day 91 and 180 (HR, 1.03; 95% CI, 0.71 to 1.51). Thereafter, PD starters again
      died at a higher rate (HR, 1.45; 95% CI, 1.07 to 1.98). These findings were more
      pronounced among patients with diabetes. Sensitivity analyses using more
      stringent criteria to ensure that first treatment choice reflected long-term
      treatment choice confirmed the presence of an association between PD and
      mortality. In conclusion, compared with HD, peritoneal dialysis appears to be
      associated with higher mortality among older patients, particularly among those
      with diabetes, even after controlling for a large number of risk factors for
      mortality, propensity scores to control for nonrandom treatment assignment, and
      center stratification.

PMID- 12191981
TI  - Excess risk of chronic kidney disease among African-American versus white
      subjects in the United States: a population-based study of potential explanatory
      factors.
AB  - African Americans experience higher rates of chronic kidney disease (CKD) than do
      whites. It was hypothesized that racial differences in modifiable factors would
      account for much of the excess risk of CKD. A cohort study of 9082 African
      American and white adults of age 30 to 74 yr, who participated in the Second
      National Health and Nutrition Examination Survey in 1976 to 1980 and were
      monitored for vital status through 1992 in the Second National Health and
      Nutrition Examination Survey Mortality Study, was conducted. Incident CKD was
      defined as treated CKD cases (ascertained by linkage to the Medicare Registry)
      and deaths related to kidney disease. The incidence of all-cause CKD was 2.7
      times higher among African Americans, compared with whites. Adjustment for
      sociodemographic factors decreased the relative risk (RR) to 2.49, explaining 12%
      of the excess risk of CKD among African Americans. Further adjustment for
      lifestyle factors explained 24% of the excess risk, whereas adjustment for
      clinical factors alone explained 32%. Simultaneous adjustment for
      sociodemographic, lifestyle, and clinical factors attenuated the RR to 1.95 (95%
      confidence interval, 1.05 to 3.63), explaining 44% of the excess risk. Although
      the excess risk of CKD among African Americans was much greater among middle-age
      adults (30 to 59 yr of age; RR = 4.23, statistically significant) than among
      older adults (60 to 74 yr of age; RR = 1.27), indicating an interaction between
      race and age, the same patterns of explanatory factors were observed for the two
      age groups. Nearly one-half of the excess risk of CKD among African-American
      adults can be explained on the basis of potentially modifiable risk factors;
      however, much of the excess risk remains unexplained.

PMID- 12191982
TI  - Capillary deposition of complement split product C4d in renal allografts is
      associated with basement membrane injury in peritubular and glomerular
      capillaries: a contribution of humoral immunity to chronic allograft rejection.
AB  - Endothelial deposition of the complement split product C4d is an established
      marker of antibody-mediated acute renal allograft rejection. A contribution of
      alloantibody-dependent immune reactions to chronic rejection is under discussion.
      In this study, the association of immunohistochemically detected endothelial C4d
      deposition in peritubular capillaries (PTC) with morphologic features of chronic
      renal allograft injury was investigated in a large study cohort. C4d deposits in
      PTC were detected in 73 (34%) of 213 late allograft biopsies performed in 213
      patients more than 12 mo after transplantation (median, 4.9 yr) because of
      chronic allograft dysfunction. Endothelial C4d deposition was found to be
      associated with chronic transplant glomerulopathy (CG) (P < 0.0001), with
      basement membrane multilayering in PTC (P = 0.01), and with an accumulation of
      mononuclear inflammatory cells in PTC (P < 0,001). Furthermore, C4d deposits in
      PTC (in biopsies with normal glomerular morphology) were associated with
      development of CG in follow-up biopsies. Other morphologic features of chronic
      allograft nephropathy (with exception of tubular atrophy) were not associated
      with C4d deposits in PTC. Analyses of previous and follow-up biopsies revealed
      that C4d deposits may occur de novo and may also disappear at any time after
      transplantation. In conclusion, the data suggest that complement activation in
      renal microvasculature, indicating humoral alloreactivity, contributes to chronic
      rejection characterized by chronic transplant glomerulopathy and basement
      membrane multilayering in PTC.

PMID- 12191983
TI  - Allergic skin and systemic reactions in a patient with pure red cell aplasia and
      anti-erythropoietin antibodies challenged with different epoetins.
AB  - Recent concern has arisen about the development of neutralizing anti
      erythropoietin (EPO) antibodies during the course of treatment with recombinant
      EPO. The underlying mechanisms are poorly understood. A patient was observed who
      developed wheals at the sites of subcutaneous injections of epoetin-alpha before
      the manifestation of pure red cell aplasia (PRCA). Intravenous application of
      different epoetins evoked skin reactions at the sites of former subcutaneous
      injections, indicating local persistence of sensitized cells, and eventually a
      systemic anaphylactoid response. Anti-EPO antibodies crossreactive with epoetin
      beta and darbepoetin-alpha were demonstrated in patient serum. PRCA gradually
      improved after treatment with prednisolone.

PMID- 12191984
TI  - Genetics and pathogenesis of polycystic kidney disease.

PMID- 12191985
TI  - Disturbances of Na/K balance: pseudohypoaldosteronism revisited.

PMID- 12191986
TI  - Chronic kidney disease and cardiovascular risk: time to focus on therapy.

PMID- 12191987
TI  - C4d and the fate of organ allografts.

PMID- 12191988
TI  - Capillary C4d deposition as a marker of humoral immunity in renal allograft
      rejection.

PMID- 12191989
TI  - The motor protein kinesin-1 links neurofibromin and merlin in a common cellular
      pathway of neurofibromatosis.
AB  - Mutations in either of the two tumor suppressor genes NF1 (neurofibromin) and NF2
      (merlin) result in Neurofibromatosis, a condition predisposing individuals to
      developing a variety of benign and malignant tumors of the central and peripheral
      nervous systems. Here we report the identification of two distinct NF1-containing
      complexes, one in the soluble and the other in the particulate fraction of HeLa
      extract. We show that the soluble NF1 complex delineates a large holo-NF1 complex
      (2 MDa) encompassing the components of a smaller particulate core-NF1 complex
      (400 kDa). Purification of the core-NF1 complex followed by mass spectrometric
      analysis revealed the motor protein, kinesin-1 heavy chain (HsuKHC/KIF5B), as a
      catalytic subunit of both NF-1-containing complexes. Importantly, although NF1
      and NF2 are not in a stable association, NF2 is also a component of a distinct
      kinesin-1-containing complex. These results point to kinesin-1 as a common
      denominator between NF1 and NF2.

PMID- 12191990
TI  - Aberrant tau phosphorylation by glycogen synthase kinase-3beta and JNK3 induces
      oligomeric tau fibrils in COS-7 cells.
AB  - Neurofibrillary tangles (NFTs) are found in a wide range of neurodegenerative
      disorders, including Alzheimer's disease. The major component of NFTs is
      aberrantly hyperphosphorylated microtubule-associated protein tau. Because
      appropriate in vivo models have been lacking, the role of tau phosphorylation in
      NFTs formation has remained elusive. Here, we describe a new model in which
      adenovirus-mediated gene expression of tau, DeltaMEKK, JNK3, and GSK-3beta in COS
      7 cells produces most of the pathological phosphorylation epitopes of tau
      including AT100. Furthermore, this co-expression resulted in the formation of tau
      aggregates having short fibrils that were detergent-insoluble and Thioflavin-S
      reactive. These results suggest that aberrant tau phosphorylation by the
      combination of these kinases may be involved in "pretangle," oligomeric tau
      fibril formation in vivo.

PMID- 12191991
TI  - Actin can act as a cofactor for a viral proteinase in the cleavage of the
      cytoskeleton.
AB  - Cytoskeletal proteins are exploited by many viruses during infection. We report a
      novel finding that actin can act as a cofactor for the adenovirus proteinase
      (AVP) in the degradation of cytoskeletal proteins. Transfection studies in HeLa
      cells revealed AVP localized with cytokeratin 18, and this was followed by
      destruction of the cytokeratin network. For AVP to cleave cytokeratin 18, a
      cellular cofactor was shown to be required, consistent with AVP being synthesized
      as an inactive proteinase. Actin was considered a cellular cofactor for AVP,
      because the C terminus of actin is homologous to a viral cofactor for AVP. AVP
      was shown to bind to the C terminus of actin, and in doing so AVP exhibited full
      enzymatic activity. In vitro, actin was a cofactor in the cleavage of cytokeratin
      18 by AVP. The proteinase alone could not cleave cytokeratin 18, but in the
      presence of actin, AVP cleaved cytokeratin 18. Indeed, actin itself was shown to
      be a cofactor and a substrate for its own destruction in that it was cleaved by
      AVP in vitro. Cleavage of cytoskeletal proteins weakens the structure of the
      cell, and therefore, actin as a cofactor may play a role in cell lysis and
      release of nascent virions.

PMID- 12191993
TI  - Transient state kinetic investigation of 5-aminolevulinate synthase reaction
      mechanism.
AB  - 5-Aminolevulinate synthase (ALAS), a pyridoxal 5'-phosphate-dependent enzyme,
      catalyzes the first, and regulatory, step of the heme biosynthetic pathway in
      nonplant eukaryotes and some bacteria. 5-Aminolevulinate synthase is a dimeric
      protein having an ordered kinetic mechanism with glycine binding before succinyl
      CoA and with aminolevulinate release after CoA and carbon dioxide. Rapid scanning
      stopped-flow absorption spectrophotometry in conjunction with multiple turnover
      chemical quenched-flow kinetic analyses and a newly developed CoA detection
      method were used to examine the ALAS catalytic reaction and identify the rate
      determining step. The reaction of glycine with ALAS follows a three-step kinetic
      process, ascribed to the formation of the Michaelis complex and the pyridoxal 5'
      phosphate-glycine aldimine, followed by the abstraction of the glycine pro-R
      proton from the external aldimine. Significantly, the rate associated with this
      third step (k(3) = 0.002 s(-1)) is consistent with the rate determined for the
      ALAS-catalyzed removal of tritium from [2-(3)H(2)]glycine. Succinyl-CoA and
      acetoacetyl-CoA increased the rate of glycine proton removal approximately
      250,000- and 10-fold, respectively, supporting our previous proposal that the
      physiological substrate, succinyl-CoA, promotes a protein conformational change,
      which accelerates the conversion of the external aldimine into the initial
      quinonoid intermediate (Hunter, G. A., and Ferreira, G. C. (1999) J. Biol. Chem.
      274, 12222-12228). Rapid scanning stopped-flow and quenched-flow kinetic analyses
      of the ALAS reaction under single turnover conditions lend evidence for two
      quinonoid reaction intermediates and a model of the ALAS kinetic mechanism in
      which product release is at least the partially rate-limiting step. Finally, the
      carbonyl and carboxylate groups of 5-aminolevulinate play a major protein
      interacting role by inducing a conformational change in ALAS and, thus, possibly
      modulating product release.

PMID- 12191994
TI  - Overexpression of the protein phosphatase 2A regulatory subunit Bgamma promotes
      neuronal differentiation by activating the MAP kinase (MAPK) cascade.
AB  - Protein serine/threonine phosphatase 2A (PP2A) is a multifunctional regulator of
      cellular signaling. Variable regulatory subunits associate with a core dimer of
      scaffolding and catalytic subunits and are postulated to dictate substrate
      specificity and subcellular location of the heterotrimeric PP2A holoenzyme. The
      role of brain-specific regulatory subunits in neuronal differentiation and
      signaling was investigated in the PC6-3 subline of PC12 cells. Endogenous Bbeta,
      Bgamma, and B'beta protein expression was induced during nerve growth factor
      (NGF)-mediated neuronal differentiation. Transient expression of Bgamma, but not
      other PP2A regulatory subunits, facilitated neurite outgrowth in the absence and
      presence of NGF. Tetracycline-inducible expression of Bgamma caused growth arrest
      and neurofilament expression, further evidence that PP2A/Bgamma can promote
      differentiation. In PC6-3 cells, but not non-neuronal cell lines, Bgamma
      specifically promoted long lasting activation of the mitogen-activated protein
      (MAP) kinase cascade, a key mediator of neuronal differentiation. Pharmacological
      and dominant-negative inhibition and kinase assays indicate that Bgamma promotes
      neuritogenesis by stimulating the MAP kinase cascade downstream of the TrkA NGF
      receptor but upstream or at the level of the B-Raf kinase. Mutational analyses
      demonstrate that the divergent N terminus is critical for Bgamma activity. These
      studies implicate PP2A/Bgamma as a positive regulator of MAP kinase signaling in
      neurons.

PMID- 12191992
TI  - Bimodal targeting of microsomal CYP2E1 to mitochondria through activation of an N
      terminal chimeric signal by cAMP-mediated phosphorylation.
AB  - Cytochrome P450 2E1 (CYP2E1) plays an important role in alcohol-induced toxicity
      and oxidative stress. Recently, we showed that this predominantly microsomal
      protein is also localized in rat hepatic mitochondria. In this report, we show
      that the N-terminal 30 amino acids of CYP2E1 contain a chimeric signal for
      bimodal targeting of the apoprotein to endoplasmic reticulum (ER) and
      mitochondria. We demonstrate that the cryptic mitochondrial targeting signal at
      sequence 21-31 of the protein is activated by cAMP-dependent phosphorylation at
      Ser-129. S129A mutation resulted in lower affinity for binding to cytoplasmic
      Hsp70, mitochondrial translocases (TOM40 and TIM44) and reduced mitochondrial
      import. S129A mutation, however, did not affect the extent of binding to the
      signal recognition particle and association with ER membrane translocator protein
      Sec61. Addition of saturating levels of signal recognition particle caused only a
      partial inhibition of CYP2E1 translation under in vitro conditions, and
      saturating levels of ER resulted only in partial membrane integration. cAMP
      enhanced the mitochondrial CYP2E1 (referred to as P450MT5) level but did not
      affect its level in the ER. Our results provide new insights on the mechanism of
      cAMP-mediated activation of a cryptic mitochondrial targeting signal and
      regulation of P450MT5 targeting to mitochondria.

PMID- 12191995
TI  - JAK-STAT signaling mediates gangliosides-induced inflammatory responses in brain
      microglial cells.
AB  - Neuronal cell membranes are particularly rich in gangliosides, which play
      important roles in brain physiology and pathology. Previously, we reported that
      gangliosides could act as microglial activators and are thus likely to
      participate in many neuronal diseases. In the present study we provide evidence
      that JAK-STAT inflammatory signaling mediates gangliosides-stimulated microglial
      activation. Both in rat primary microglia and murine BV2 microglial cells,
      gangliosides stimulated nuclear factor binding to GAS/ISRE elements, which are
      known to be STAT-binding sites. Consistent with this, gangliosides rapidly
      activated JAK1 and JAK2 and induced phosphorylation of STAT1 and STAT3. In
      addition, gangliosides increased transcription of the inflammation-associated
      genes inducible nitric-oxide synthase, ICAM-1, and MCP-1, which are reported to
      contain STAT-binding elements in their promoter regions. AG490, a JAK inhibitor,
      reduced induction of these genes, nuclear factor binding activity, and activation
      of STAT1 and -3 in gangliosides-treated microglia. AG490 also inhibited
      gangliosides-induced release of nitric oxide, an inflammation hallmark.
      Furthermore, AG490 markedly reduced activation of ERK1/2 MAPK, indicating that
      ERKs act downstream of JAK-STAT signaling during microglial activation. However,
      AG490 did not affect activation of p38 MAPK. We also report that the sialic acid
      residues present on gangliosides may be one of the essential components in
      activation of JAK-STAT signaling. The present study indicates that JAK-STAT
      signaling is an early event in gangliosides-induced brain inflammatory responses.

PMID- 12191996
TI  - GTP-yeast actin.
AB  - Because of the apparently greater conformational flexibility of yeast versus
      muscle actin and the ability of other members in the actin protein superfamily to
      efficiently use both ATP and GTP, we assessed the ability of yeast actin to
      function with GTP. Etheno-ATP exchange studies showed that the binding of GTP to
      yeast actin is about 1/9 as tight as that of ATP in contrast to the 1/1,240 ratio
      for muscle actin. Proteolysis of GTP-bound G-yeast actin suggests that the
      conformation of subdomain 2 is very much like that of ATP-bound actin, but CD
      studies show that GTP-bound actin is less thermostable than ATP-bound actin. GTP
      actin polymerizes with an apparent critical concentration of 1.5 microm, higher
      than that of ATP-actin (0.3 microm) although filament structures observed by
      electron microscopy were similar. Yeast actin hydrolyzes GTP in a polymerization
      dependent manner, and GTP-bound F-actin decorates with the myosin S1. Conversion
      of Phe(306) in the nucleotide binding site to the Tyr found in muscle actin
      raised the nucleotide discrimination ratio from the 1/9 of wild-type actin to
      1/125. This result agrees with modeling that predicts that removal of the Tyr
      hydroxyl will create a space for the C2 amino group of the GTP guanine.

PMID- 12191997
TI  - Carbohydrate-binding modules recognize fine substructures of cellulose.
AB  - Competition isotherms are used to identify the set of cellulose substructures to
      which cellulose binding modules (CBMs) from families 2a, 3, 4, 9, and 17 bind.
      The experiments are based on coupling a unique fluorescent tag to each CBM in a
      manner that does not alter the natural binding properties of the CBM and
      therefore allows the surface and solution concentrations of each CBM to be
      monitored as a function of time and composition. Adsorption and surface exchange
      of like or competing CBMs are monitored using a range of cellulose preparations
      varying in both crystallinity and provenance. CBMs from families 2a, 3, 4, 9, and
      17 are shown to recognize different physical forms of prepared cellulose. The
      demonstration of the very fine binding specificity of cellulose-specific CBMs
      implies that the polysaccharide targets of CBMs extend down to the resolution of
      cellulose microstructures.

PMID- 12191998
TI  - Complement C5b-9 membrane attack complex increases expression of endoplasmic
      reticulum stress proteins in glomerular epithelial cells.
AB  - In the passive Heymann nephritis (PHN) model of membranous nephropathy,
      complement C5b-9 induces glomerular epithelial cell (GEC) injury, proteinuria,
      and activation of cytosolic phospholipase A(2) (cPLA(2)). This study addresses
      the role of endoplasmic reticulum (ER) stress proteins (bip, grp94) in GEC
      injury. GEC that overexpress cPLA(2) (produced by transfection) and "neo" GEC
      (which expresses cPLA(2) at a lower level) were incubated with complement (40
      min), and leakage of constitutively expressed bip and grp94 from ER into cytosol
      was measured to monitor ER injury. Greater leakage of bip and grp94 occurred in
      complement-treated GEC that overexpress cPLA(2), as compared with neo, implying
      that cPLA(2) activation perturbed ER membrane integrity. After chronic incubation
      (4-24 h), C5b-9 increased bip and grp94 mRNAs and proteins, and the increases
      were dependent on cPLA(2). Expression of bip-antisense mRNA reduced stimulated
      bip protein expression and enhanced complement-dependent GEC injury. Glomerular
      bip and grp94 proteins were up-regulated in proteinuric rats with PHN, as
      compared with normal control. Pretreatment of rats with tunicamycin or
      adriamycin, which increase ER stress protein expression, reduced proteinuria in
      PHN. Thus, C5b-9 injures the ER and enhances ER stress protein expression, in
      part, via activation of cPLA(2). ER stress protein induction is a novel mechanism
      of protection from complement attack.

PMID- 12192000
TI  - REST repression of neuronal genes requires components of the hSWI.SNF complex.
AB  - A function of the transcription factor REST is to block the expression of
      neuronal phenotypic traits in non-neuronal cells. Previous studies have shown
      that REST-mediated repression requires histone deacetylase activity and that
      recruitment of deacetylases is mediated by two co-repressors, Sin3A and CoREST.
      In this study, we show that a repressor domain in CoREST interacts with BRG1
      associated factor (BAF) 57, a component of the hSWI.SNF complex. In vivo, BAF57
      occupies the neuronal sodium channel gene (Nav1.2) promoter, and targeting to
      this gene requires REST. In addition to BAF57, the ATPase BRG1 and BAF170, other
      members of the hSWI.SNF complex, are also present in the REST.CoREST repressor
      complex. Microinjection of specific antibodies against BRG1, BAF57, or BAF170
      into Rat1 fibroblasts relieves repression of RE1 reporter genes. Together, our
      data suggest that ATP-dependent chromatin remodeling, as well as histone
      deacetylation, is needed for REST-mediated repression.

PMID- 12191999
TI  - Rescue of embryonic epithelium reveals that the homozygous deletion of the
      retinoblastoma gene confers growth factor independence and immortality but does
      not influence epithelial differentiation or tissue morphogenesis.
AB  - The ability to rescue viable prostate precursor tissue from retinoblastoma
      deficient (Rb-/-) fetal mice has allowed for the isolation and characterization
      of the first Rb-/- prostate epithelial cell line. This cell line, designated Rb-/
      PrE, was utilized for experiments examining the consequences of Rb loss on an
      epithelial population. These findings demonstrated that Rb deletion has no
      discernible effect on prostatic histodifferentiation in Rb-/-PrE cultures. When
      Rb-/-PrE cells were recombined with embryonic rat urogenital mesenchyme and
      implanted into athymic male, nude mouse hosts, the recombinants developed into
      fully differentiated and morphologically normal prostate tissue. The Rb-/-PrE
      phenotype was characterized by serum independence in culture and immortality in
      vivo, when compared with wild type controls. Cell cycle analysis revealed
      elevated S phase DNA content accompanied by increased expression of cyclin E1 and
      proliferating cell nuclear antigen. Rb-/-PrE cultures also exhibited a diminished
      ability to growth arrest under high density culture conditions. We believe that
      the development of Rb-/- prostate tissue and cell lines has provided a unique
      experimental platform with which to investigate the consequences of Rb deletion
      in epithelial cells under various physiological conditions. Additionally, the
      development of this technology will allow similar studies in other tissues and
      cell populations rescued from Rb-/- fetuses.

PMID- 12192001
TI  - Functional characterization of choline monooxygenase, an enzyme for betaine
      synthesis in plants.
AB  - In plants, the first step in betaine synthesis was shown to be catalyzed by a
      novel Rieske-type iron-sulfur enzyme, choline monooxygenase (CMO). Although CMO
      so far has been found only in Chenopodiaceae and Amaranthaceae, the recent genome
      sequence suggests the presence of a CMO-like gene in Arabidopsis, a betaine non
      accumulating plant. Here, we examined the functional properties of CMO expressed
      in Escherichia coli, cyanobacterium, and Arabidopsis thaliana. We found that E.
      coli cells in which choline dehydrogenase (CDH) was replaced with spinach CMO
      accumulate betaine and complement the salt-sensitive phenotype of the CDH-deleted
      E. coli mutant. Changes of Cys-181 in spinach CMO to Ser, Thr, and Ala and His
      287 to Gly, Val, and Ala abolished the accumulation of betaine. The Arabidopsis
      CMO-like gene was transcribed in Arabidopsis, but its protein was not detected.
      When the Arabidopsis CMO-like gene was expressed in E. coli, the protein was
      detected but was found not to promote betaine sysnthesis. Overexpression of
      spinach CMO in E. coli, Synechococcus sp. PCC7942, and Arabidopsis conferred
      resistance to abiotic stress. These facts clearly indicate that CMO, but not the
      CMO-like protein, could oxidize choline and that Cys-181 and His-287 are involved
      in the binding of Fe-S cluster and Fe, respectively.

PMID- 12192002
TI  - Biophysical characterization of the alpha-globin binding protein alpha-hemoglobin
      stabilizing protein.
AB  - Alpha-hemoglobin stabilizing protein (AHSP) is a small (12 kDa) and abundant
      erythroid-specific protein that binds specifically to free alpha-(hemo)globin and
      prevents its precipitation. When present in excess over beta-globin, its normal
      binding partner, alpha-globin can have severe cytotoxic effects that contribute
      to important human diseases such as beta-thalassemia. Because AHSP might act as a
      chaperone to prevent the harmful aggregation of alpha-globin during normal
      erythroid cell development and in diseases of globin chain imbalance, it is
      important to characterize the biochemical properties of the AHSP.alpha-globin
      complex. Here we provide the first structural information about AHSP and its
      interaction with alpha-globin. We find that AHSP is a predominantly alpha-helical
      globular protein with a somewhat asymmetric shape. AHSP and alpha-globin are both
      monomeric in solution as determined by analytical ultracentrifugation and bind
      each other to form a complex with 1:1 subunit stoichiometry, as judged by gel
      filtration and amino acid analysis. We have used isothermal titration calorimetry
      to show that the interaction is of moderate affinity with an association constant
      of 1 x 10(7) m(-1) and is thus likely to be biologically significant given the
      concentration of AHSP (approximately 0.1 mm) and hemoglobin (approximately 4 mm)
      in the late pro-erythroblast.

PMID- 12192003
TI  - Cloning and functional characterization of a novel aquaporin from Xenopus laevis
      oocytes.
AB  - We have cloned a novel aquaporin (AQP) from Xenopus laevis oocytes, which we have
      provisionally named AQPxlo. The predicted protein showed highest homology (39
      50%) to aquaglyceroporins. Northern blot analysis showed strong hybridization to
      an approximately 1.4-kb transcript in X. laevis fat body and oocytes, whereas a
      weaker signal was obtained in kidney. We injected in vitro transcribed cRNA
      encoding AQPxlo into Xenopus oocytes for functional characterization. AQPxlo
      expression increased osmotic water permeability (P(f)), as well as the uptake of
      glycerol and urea. However, AQPxlo excluded larger polyols and thiourea. An
      alkaline extracellular pH (pH(o)) increased P(f) and to a lesser extent urea
      uptake but not glycerol uptake. Remarkably, low HgCl(2) concentrations (0.3-10
      microm) reduced P(f) and urea uptake, whereas high concentrations (300-1000
      microm) reversed the inhibition. We propose that AQPxlo is a new AQP paralogue
      unknown in mammals.

PMID- 12192004
TI  - Mouse geminin inhibits not only Cdt1-MCM6 interactions but also a novel intrinsic
      Cdt1 DNA binding activity.
AB  - DNA replication is controlled by the stepwise assembly of a pre-replicative
      complex and the replication apparatus. Cdt1 is a novel component of the pre
      replicative complex and plays a role in loading the minichromosome maintenance
      (MCM) 2-7 complex onto chromatin. Cdt1 activity is inhibited by geminin, which is
      essential for the G(2)/M transition in metazoan cells. To understand the
      molecular basis of the Cdt1-geminin regulatory mechanism in mammalian cells, we
      cloned and expressed the mouse Cdt1 homologue cDNA in bacterial cells and
      purified mouse Cdt1 to near homogeneity. We found by yeast two-hybrid analysis
      that mouse Cdt1 associates with geminin, MCM6, and origin recognition complex 2.
      MCM6 interacts with the Cdt1 carboxyl-terminal region (amino acids 407-477),
      which is conserved among eukaryotes, whereas geminin associates with the Cdt1
      central region (amino acids 177-380), which is conserved only in metazoans. In
      addition, we found that Cdt1 can bind DNA in a sequence-, strand-, and
      conformation-independent manner. The Cdt1 DNA binding domain overlaps with the
      geminin binding domain, and the binding of Cdt1 to DNA is inhibited by geminin.
      Taken together, we have defined structural domains and novel biochemical
      properties for mouse Cdt1 that suggest that Cdt1 behaves as an intrinsic DNA
      binding factor in the pre-replicative complex.

PMID- 12192005
TI  - Collagen dissolution by keratinocytes requires cell surface plasminogen
      activation and matrix metalloproteinase activity.
AB  - Matrix metalloproteinase-14 is required for degradation of fibrillar collagen by
      mesenchymal cells. Here we show that keratinocytes use an alternative plasminogen
      and matrix metalloproteinase-13-dependent pathway for dissolution of collagen
      fibrils. Primary keratinocytes displayed an absolute requirement for serum to
      dissolve collagen. Dissolution of collagen was abolished in plasminogen-depleted
      serum and could be restored by the exogenous addition of plasminogen. Both
      plasminogen activator inhibitor-1 and tissue inhibitor of metalloproteinase
      blocked collagen dissolution, demonstrating the requirement of both plasminogen
      activation and matrix metalloproteinase activity for degradation. Cell surface
      plasmin activity was critical for the degradation process as aprotinin, but not
      alpha(2)-antiplasmin, prevented collagen dissolution. Keratinocytes with single
      deficiencies in either urokinase or tissue plasminogen activator retained the
      ability to dissolve collagen. However, collagen fibril dissolution was abolished
      in keratinocytes with a combined deficiency in both urokinase and tissue
      plasminogen activator. Combined, but not single, urokinase and tissue plasminogen
      activator deficiency also completely blocked the activation of the fibrillar
      collagenase, matrix metalloproteinase-13, by keratinocytes. The activation of
      matrix metalloproteinase-13 in normal keratinocytes was prevented by plasminogen
      activator inhibitor-1 and aprotinin but not by tissue inhibitor of
      metalloproteinase-1 and -2, suggesting that plasmin activates matrix
      metalloproteinase-13 directly. We propose that plasminogen activation facilitates
      keratinocyte-mediated collagen breakdown via the direct activation of matrix
      metalloproteinase-13 and possibly other fibrillar collagenases.

PMID- 12192006
TI  - Metalloenzyme-like activity of Alzheimer's disease beta-amyloid. Cu-dependent
      catalytic conversion of dopamine, cholesterol, and biological reducing agents to
      neurotoxic H(2)O(2).
AB  - Beta-amyloid (Abeta) 1-42, implicated in the pathogenesis of Alzheimer's disease,
      forms an oligomeric complex that binds copper at a CuZn superoxide dismutase-like
      binding site. Abeta.Cu complexes generate neurotoxic H(2)O(2) from O(2) through
      Cu(2+) reduction, but the reaction mechanism has been unclear. We now report that
      Abeta1-42, when binding up to 2 eq of Cu(2+), generates the H(2)O(2)
      catalytically by recruiting biological reducing agents as substrates under
      conditions where the Cu(2+) or reducing agents will not form H(2)O(2) themselves.
      Cholesterol is an important substrate for this activity, as are vitamin C, L
      DOPA, and dopamine (V(max) for dopamine = 34.5 nm/min, K(m) = 8.9 microm). The
      activity was inhibited by anti-Abeta antibodies, Cu(2+) chelators, and Zn(2+).
      Toxicity of Abeta in neuronal culture was consistent with catalytic H(2)O(2)
      production. Abeta was not toxic in cell cultures in the absence of Cu(2+), and
      dopamine (5 microm) markedly exaggerated the neurotoxicity of 200 nm Abeta1
      42.Cu. Therefore, microregional catalytic H(2)O(2) production, combined with the
      exhaustion of reducing agents, may mediate the neurotoxicity of Abeta in
      Alzheimer's disease, and inhibitors of this novel activity may be of therapeutic
      value.

PMID- 12192007
TI  - Mechanistic characterization of Toxoplasma gondii thymidylate synthase (TS-DHFR)
      dihydrofolate reductase. Evidence for a TS intermediate and TS half-sites
      reactivity.
AB  - This study describes the use of rapid transient kinetic methods to characterize
      the bifunctional thymidylate synthase-dihydrofolate reductase (TS-DHFR) enzyme
      from Toxoplasma gondii. In addition to elucidating the detailed kinetic scheme
      for this enzyme, this work provides the first direct kinetic evidence for the
      formation of a TS intermediate and for half-sites TS reactivity in human and
      Escherichia coli monofunctional TS and in T. gondii and Leishmania major
      bifunctional TS-DHFR. Comparison of the T. gondii TS-DHFR catalytic mechanism to
      that of the L. major enzyme reveals the mechanistic differences to be
      predominantly in DHFR activity. Specifically, TS ligand induced domain-domain
      communication involving DHFR activation is observed only in the L. major enzyme
      and, whereas both DHFR activities involve a rate-limiting conformational change,
      the change occurs at different positions along the kinetic pathway.

PMID- 12192008
TI  - Yeast flavohemoglobin from Candida norvegensis. Its structural, spectral, and
      stability properties.
AB  - Flavohemoglobin was isolated directly from the yeast Candida norvegensis and
      studied on its structural, spectral, and stability properties. In Candida
      flavohemoglobin, the 155 N-terminal residues make a heme-containing domain, while
      the remaining 234 C-terminal residues serve as a FAD-containing reductase domain.
      A pair of His-95 and Gln-63 was assigned to the proximal and distal residues,
      respectively. In purification procedure FAD was partially dissociated on a Butyl
      Toyopearl column, so that FAD-lacking flavohemoglobin was also obtainable. In
      this ferric species, the Soret and charge-transfer bands were all characteristic
      of a penta-coordinate form. Compared with the recombinant heme domain expressed
      in Escherichia coli, we have measured the autoxidation rate over a wide pH range.
      The resulting pH dependence curves were then analyzed in terms of a nucleophilic
      displacement mechanism. As a result, the heme domain was found to be extremely
      susceptible to autoxidation, its rate being more than 100 times higher than that
      of sperm whale MbO2. However, this inherently high oxidation rate was
      dramatically suppressed in Candida flavohemoglobin to an extent almost comparable
      to the stability of mammalian myoglobins. These new findings lead us to conclude
      that Candida flavohemoglobin, differently from bacterial flavohemoglobins, can
      serve as an oxygen storage protein in aerobic conditions.

PMID- 12192009
TI  - Purification of a modified form of bovine antithrombin III as an HIV-1 CD8+ T
      cell antiviral factor.
AB  - CD8(+) T-cells secrete soluble factor(s) capable of inhibiting both R5- and X4
      tropic strains of human immunodeficiency virus type 1 (HIV-1). CCR5 chemokine
      ligands, released from activated CD8(+) T-cells, contribute to the antiviral
      activity of these cells. These CC-chemokines, however, do not account for all
      CD8(+) T-cell antiviral factor(s) (CAF) released from these cells, particularly
      because the elusive CAF can inhibit the replication of X4 HIV-1 strains that use
      CXCR4 and not CCR5 as a coreceptor. Here we demonstrate that activated CD8(+) T
      cells of HIV-1-seropositive individuals modify serum bovine antithrombin III into
      an HIV-1 inhibitory factor capable of suppressing the replication of X4 HIV-1.
      These data indicate that antithrombin III may play a role in the progression of
      HIV-1 disease.

PMID- 12192010
TI  - Sequence requirements in the catalytic core of the "10-23" DNA enzyme.
AB  - A systematic mutagenesis study of the "10-23" DNA enzyme was performed to analyze
      the sequence requirements of its catalytic domain. Therefore, each of the 15 core
      nucleotides was substituted separately by the remaining three naturally occurring
      nucleotides. Changes at the borders of the catalytic domain led to a dramatic
      loss of enzymatic activity, whereas several nucleotides in between could be
      exchanged without severe effects. Thymidine at position 8 had the lowest degree
      of conservation and its substitution by any of the other three nucleotides caused
      only a minor loss of activity. In addition to the standard nucleotides
      (adenosine, guanosine, thymidine, or cytidine) modified nucleotides were used to
      gain further information about the role of individual functional groups. Again,
      thymidine at position 8 as well as some other nucleotides could be substituted by
      inosine without severe effects on the catalytic activity. For two positions,
      additional experiments with 2-aminopurine and deoxypurine, respectively, were
      performed to obtain information about the specific role of functional groups. In
      addition to sequence-function relationships of the DNA enzyme, this study
      provides information about suitable sites to introduce modified nucleotides for
      further functional studies or for internal stabilization of the DNA enzyme
      against endonucleolytic attack.

PMID- 12192011
TI  - Thermal unfolding of soybean peroxidase. Appropriate high denaturant
      concentrations induce cooperativity allowing the correct measurement of
      thermodynamic parameters.
AB  - We have earlier reported that both guanidine hydrochloride (GdnHCl)-induced and
      heat-induced unfolding of seed coat soybean peroxidase (SBP), monitored by far UV
      CD, show single step transition. However, although GdnHCl-induced unfolding
      follows a two-state pathway, the heat-induced denaturation proceeds through
      intermediates as indicated by the very low cooperativity of transition. In the
      former case, analysis of the data based on the two-state model gives true
      thermodynamic parameters, whereas underestimated values are obtained in the
      latter case. Available complex equations also cannot be applied for the analysis
      of the thermal unfolding of SBP due to the absence of separate transitions for
      the intermediates. In the present study, we report a method to obtain true
      thermodynamic parameters from thermal transition curves of SBP using the two
      state model. When SBP is subjected to thermal unfolding at high GdnHCl
      concentrations (5.8-6.9 M), cooperative behavior is observed, which allowed the
      analysis by the two-state model to determine their thermodynamic parameters. We
      then obtained the thermodynamic parameters in the absence of GdnHCl by
      extrapolating the graph of linear dependence of DeltaH(m) on T(m) to the T(m)
      corresponding to 0 m GdnHCl. Another key point for checking the validity of our
      method was the fact that the unfolded state of SBP generated by either heat or
      GdnHCl is the same by which we could cross-check our results with that obtained
      from GdnHCl unfolding. Having obtained the true thermodynamic parameters, we
      report a detailed thermodynamic study of SBP. Further we address the effect of
      heme in the thermal unfolding mechanism of SBP.

PMID- 12192012
TI  - Angioplasty versus minimally invasive bypass surgery.

PMID- 12192013
TI  - Beyond Barcelona--the global response to HIV.

PMID- 12192014
TI  - An outbreak of Escherichia coli O157:H7 infections among visitors to a dairy
      farm.
AB  - BACKGROUND: Outbreaks of Escherichia coli O157:H7 infections have involved direct
      transmission from animals and their environment to humans. We describe an
      outbreak among visitors to a Pennsylvania dairy and petting farm that provides
      public access to animals. METHODS: We conducted both a case-control study among
      visitors to a farm to identify risk factors for infection and a household survey
      to determine the rates of diarrheal illness among these visitors. We performed an
      extensive environmental study to identify sources of E. coli O157:H7 on the farm.
      RESULTS: Fifty-one patients with confirmed or suspected E. coli O157:H7 infection
      were enrolled in the case-control study. The median age of the patients was four
      years, and the hemolytic-uremic syndrome developed in eight. Contact with calves
      and their environment was associated with an increased risk of infection, whereas
      hand washing was protective. The household survey indicated that visitors to the
      farm during the outbreak had higher than expected rates of diarrhea.
      Environmental studies showed that 28 of the 216 cattle on the farm (13 percent)
      were colonized with E. coli O157:H7 that had the same distinct pattern on pulsed
      field gel electrophoresis that was found in isolates from the patients. This
      organism was also recovered from surfaces that were accessible to the public.
      CONCLUSIONS: In a large outbreak of E. coli O157:H7 infections among visitors to
      a dairy farm, predominantly children, high rates of carriage of E. coli O157:H7
      among calves and young cattle most likely resulted in contamination of both the
      animals' hides and the environment.

PMID- 12192015
TI  - Comparison of stenting with minimally invasive bypass surgery for stenosis of the
      left anterior descending coronary artery.
AB  - BACKGROUND: Minimally invasive bypass surgery and coronary-artery stenting are
      both accepted treatments for isolated stenosis of the proximal left anterior
      descending coronary artery. We compared the clinical outcomes after these two
      procedures. METHODS: A total of 220 symptomatic patients with high-grade lesions
      in the proximal left anterior descending coronary artery were randomly assigned
      to treatment--110 to surgery and 110 to stenting. The combined clinical end point
      was freedom from major adverse cardiac events, such as death from cardiac causes,
      myocardial infarction, and the need for repeated revascularization of the target
      lesion within six months. RESULTS: A major adverse cardiac event occurred in 31
      percent of patients after stenting, as compared with 15 percent in the surgery
      group (P=0.02). The difference was predominantly due to a higher rate of repeated
      revascularization of the target vessel for restenosis after stenting (29 percent
      vs. 8 percent, P=0.003). The combined rates of death and myocardial infarction
      did not differ significantly between groups (3 percent in the stenting group and
      6 percent in the surgery group, P=0.50). Adverse events occurred more frequently
      after surgery. The percentage of patients free from angina after six months was
      79 percent in the surgery group, as compared with 62 percent in the stenting
      group (P=0.03). CONCLUSIONS: In patients with isolated high-grade lesions of the
      proximal left anterior descending artery, both minimally invasive bypass surgery
      and stenting are effective. Stenting yields excellent short-term results with
      fewer periprocedural adverse events, but surgery is superior with regard to the
      need for repeated intervention in the target vessel and freedom from angina at
      six months of follow-up.

PMID- 12192016
TI  - Twenty-five-year follow-up of a randomized trial comparing radical mastectomy,
      total mastectomy, and total mastectomy followed by irradiation.
AB  - BACKGROUND: In women with breast cancer, the role of radical mastectomy, as
      compared with less extensive surgery, has been a matter of debate. We report 25
      year findings of a randomized trial initiated in 1971 to determine whether less
      extensive surgery with or without radiation therapy was as effective as the
      Halsted radical mastectomy. METHODS: A total of 1079 women with clinically
      negative axillary nodes underwent radical mastectomy, total mastectomy without
      axillary dissection but with postoperative irradiation, or total mastectomy plus
      axillary dissection only if their nodes became positive. A total of 586 women
      with clinically positive axillary nodes either underwent radical mastectomy or
      underwent total mastectomy without axillary dissection but with postoperative
      irradiation. Kaplan-Meier and cumulative-incidence estimates of outcome were
      obtained. RESULTS: No significant differences were observed among the three
      groups of women with negative nodes or between the two groups of women with
      positive nodes with respect to disease-free survival, relapse-free survival,
      distant-disease-free survival, or overall survival. Among women with negative
      nodes, the hazard ratio for death among those who were treated with total
      mastectomy and radiation as compared with those who underwent radical mastectomy
      was 1.08 (95 percent confidence interval, 0.91 to 1.28; P=0.38), and the hazard
      ratio for death among those who had total mastectomy without radiation as
      compared with those who underwent radical mastectomy was 1.03 (95 percent
      confidence interval, 0.87 to 1.23; P=0.72). Among women with positive nodes, the
      hazard ratio for death among those who underwent total mastectomy and radiation
      as compared with those who underwent radical mastectomy was 1.06 (95 percent
      confidence interval, 0.89 to 1.27; P=0.49). CONCLUSIONS: The findings validate
      earlier results showing no advantage from radical mastectomy. Although
      differences of a few percentage points cannot be excluded, the findings fail to
      show a significant survival advantage from removing occult positive nodes at the
      time of initial surgery or from radiation therapy.

PMID- 12192017
TI  - Paternal inheritance of mitochondrial DNA.

PMID- 12192018
TI  - Images in clinical medicine. Coronary-stent fracture.

PMID- 12192019
TI  - Experiences of Oregon nurses and social workers with hospice patients who
      requested assistance with suicide.
AB  - BACKGROUND: Oregon's 1997 Death with Dignity Act legalizes physician-assisted
      suicide. To date, information about patients who have requested this option has
      come from surveys of physicians. Although 78 percent of the 91 Oregonians who
      have died by assisted suicide were enrolled in hospice programs, there is little
      information about the experiences of hospice practitioners with these patients.
      METHODS: In 2001, we mailed a questionnaire to all hospice nurses and social
      workers in Oregon. RESULTS: Of 545 eligible hospice nurses and social workers,
      397 (73 percent) returned the survey, including 71 percent of nurses and 78
      percent of social workers. Since November 1997, 179 of the respondents (45
      percent) had cared for a patient who requested assistance with suicide. Hospice
      nurses reported on 82 patients who had received prescriptions for lethal
      medication. Ninety-eight percent of the nurses had discussed the request with a
      coworker, and 77 percent of the requests had been presented at a hospice
      interdisciplinary conference on patient care. A very important reason for the
      request was to control the circumstances of death. The least important reasons
      included depression, lack of social support, and fear of being a financial drain
      on family members. Although the patients were concerned about burdening others,
      only 11 percent of hospice nurses rated their family caregivers as more burdened
      than family caregivers for other hospice patients. CONCLUSIONS: Since assisted
      suicide was legalized in Oregon, many hospice nurses and social workers have
      provided care for a patient who requested assistance with suicide. They rated
      desire for control as a very important reason for these requests.

PMID- 12192020
TI  - Thrombotic microangiopathies.

PMID- 12192021
TI  - Case record of the Massachusetts General Hospital. Weekly clinicopathological
      exercises. Case 26-2002. An 87-year-old woman with abdominal pain, vomiting,
      bloody diarrhea, and an abdominal mass.

PMID- 12192022
TI  - Escherichia coli O157:H7--piecing together the jigsaw puzzle.

PMID- 12192023
TI  - Another surprise from the mitochondrial genome.

PMID- 12192024
TI  - Gene therapy for severe combined immunodeficiency disease.

PMID- 12192025
TI  - Erythromycin-resistant group A streptococci.

PMID- 12192026
TI  - Transplantation of the right hepatic lobe.

PMID- 12192027
TI  - Sulindac in familial adenomatous polyposis.

PMID- 12192028
TI  - Luxury primary care.

PMID- 12192029
TI  - Botulinum toxin, sweating, and body odor.

PMID- 12192030
TI  - Bradykinin-mediated angioedema.

PMID- 12192032
TI  - Classification of human B-ZIP proteins based on dimerization properties.

PMID- 12192033
TI  - The requirement for ATP hydrolysis by Saccharomyces cerevisiae Rad51 is bypassed
      by mating-type heterozygosity or RAD54 in high copy.
AB  - Rad51 can promote extensive strand exchange in vitro in the absence of ATP
      hydrolysis, and the Rad51-K191R mutant protein, which can bind but poorly
      hydrolyze ATP, also promotes strand exchange. A haploid strain expressing the
      rad51-K191R allele showed an equivalent sensitivity at low doses of ionizing
      radiation to rad51-K191A or rad51 null mutants and was defective in spontaneous
      and double-strand break-induced mitotic recombination. However, the rad51
      K191R/rad51-K191R diploid sporulated and the haploid spores showed high
      viability, indicating no apparent defect in meiotic recombination. The DNA repair
      defect caused by the rad51-K191R allele was suppressed in diploids and by mating
      type heterozygosity in haploids. RAD54 expressed from a high-copy-number plasmid
      also suppressed the gamma-ray sensitivity of rad51-K191R haploids. The
      suppression by mating-type heterozygosity of the DNA repair defect conferred by
      the rad51-K191R allele could occur by elevated expression of factors that act to
      stabilize, or promote catalysis, by the partially functional Rad51-K191R protein.

PMID- 12192034
TI  - Binding of Acf1 to DNA involves a WAC motif and is important for ACF-mediated
      chromatin assembly.
AB  - ACF is a chromatin-remodeling complex that catalyzes the ATP-dependent assembly
      of periodic nucleosome arrays. This reaction utilizes the energy of ATP
      hydrolysis by ISWI, the smaller of the two subunits of ACF. Acf1, the large
      subunit of ACF, is essential for the full activity of the complex. We performed a
      systematic mutational analysis of Acf1 to elucidate the functions of specific
      subregions of the protein. These studies revealed DNA- and ISWI-binding regions
      that are important for the chromatin assembly and ATPase activities of ACF. The
      DNA-binding region of Acf1 includes a WAC motif, which is necessary for the
      efficient binding of ACF complex to DNA. The interaction of Acf1 with ISWI
      requires a DDT domain, which has been found in a variety of transcription and
      chromatin-remodeling factors. Chromatin assembly by ACF is also impaired upon
      mutation of an acidic region in Acf1, which may interact with histones during the
      deposition process. Lastly, we observed modest chromatin assembly defects on
      mutation of other conserved sequence motifs. Thus, Acf1 facilitates chromatin
      assembly via an N-terminal DNA-binding region with a WAC motif, a central ISWI
      binding segment with a DDT domain, and a C-terminal region with an acidic
      stretch, a WAKZ motif, PHD fingers, and bromodomain.

PMID- 12192035
TI  - Mechanism of rapid transcriptional induction of tumor necrosis factor alpha
      responsive genes by NF-kappaB.
AB  - NF-kappaB induces the expression of genes involved in immune response, apoptosis,
      inflammation, and the cell cycle. Certain NF-kappaB-responsive genes are
      activated rapidly after the cell is stimulated by cytokines and other
      extracellular signals. However, the mechanism by which these genes are activated
      is not entirely understood. Here we report that even though NF-kappaB interacts
      directly with TAF(II)s, induction of NF-kappaB by tumor necrosis factor alpha
      (TNF-alpha) does not enhance TFIID recruitment and preinitiation complex
      formation on some NF-kappaB-responsive promoters. These promoters are bound by
      the transcription apparatus prior to TNF-alpha stimulus. Using the immediate
      early TNF-alpha-responsive gene A20 as a prototype promoter, we found that the
      constitutive association of the general transcription apparatus is mediated by
      Sp1 and that this is crucial for rapid transcriptional induction by NF-kappaB. In
      vitro transcription assays confirmed that NF-kappaB plays a postinitiation role
      since it enhances the transcription reinitiation rate whereas Sp1 is required for
      the initiation step. Thus, the consecutive effects of Sp1 and NF-kappaB on the
      transcription process underlie the mechanism of their synergy and allow rapid
      transcriptional induction in response to cytokines.

PMID- 12192036
TI  - Fer kinase is required for sustained p38 kinase activation and maximal chemotaxis
      of activated mast cells.
AB  - Mast cells play important roles in inflammation and immunity and express the high
      affinity immunoglobulin E receptor (Fc epsilon RI) and the receptor protein
      tyrosine kinase Kit. Aggregation of Fc epsilon RI via antigen binding elicits
      signals leading to the release of preformed inflammatory mediators as well as de
      novo-synthesized lipid mediators and cytokines and to elevated cell adhesion and
      migration. Here, we report that in mouse bone marrow-derived mast cells, Fer
      kinase is activated downstream of activated Fc epsilon RI and activated Kit
      receptor, and this activation is abolished in cells homozygous for a kinase
      inactivating mutation in Fer (fer(DR/DR)). Interestingly, the highly related
      Fps/Fes kinase is also activated upon Fc epsilon RI aggregation. This report
      represents the first description of a common signaling pathway activating Fer and
      Fps/Fes. While Fer-deficient cells showed similar activation of the Erk mitogen
      activated protein (MAP) kinases, p38 MAP kinase activation was less sustained
      than that in wild-type cells. Although no major defects were observed in
      degranulation, leukotriene biosynthesis, and cytokine secretion, Fer-deficient
      cells displayed increased adhesion and decreased motility upon activation of Fc
      epsilon RI and the Kit receptor. The restoration of Fer kinase activity in
      fer(DR/DR) mast cells resulted in prolonged p38 kinase activation and increased
      antigen-mediated cell migration of sensitized mast cells. Thus, Fer is required
      for maximal p38 kinase activation to promote the chemotaxis of activated mast
      cells. Further studies with mast cells derived from fps/fes-deficient mice will
      be required to provide insight into the role of Fps/Fes in mast cell activation.

PMID- 12192038
TI  - Characterization of RAD51-independent break-induced replication that acts
      preferentially with short homologous sequences.
AB  - Repair of double-strand breaks by gene conversions between homologous sequences
      located on different Saccharomyces cerevisiae chromosomes or plasmids requires
      RAD51. When repair occurs between inverted repeats of the same plasmid, both
      RAD51-dependent and RAD51-independent repairs are found. Completion of RAD51
      independent plasmid repair events requires RAD52, RAD50, RAD59, TID1 (RDH54), and
      SRS2 and appears to involve break-induced replication coupled to single-strand
      annealing. Surprisingly, RAD51-independent recombination requires much less
      homology (30 bp) for strand invasion than does RAD51-dependent repair
      (approximately 100 bp); in fact, the presence of Rad51p impairs recombination
      with short homology. The differences between the RAD51- and RAD50/RAD59-dependent
      pathways account for the distinct ways that two different recombination processes
      maintain yeast telomeres in the absence of telomerase.

PMID- 12192037
TI  - Novel translational control through an iron-responsive element by interaction of
      multifunctional protein YB-1 and IRP2.
AB  - The eukaryotic Y-box-binding protein YB-1 functions in various biological
      processes, including DNA repair, cell proliferation, and transcriptional and
      translational controls. To gain further insight into how human YB-1 plays its
      role in pleiotropic functions, we here used two-hybrid screenings to identify
      partners of this protein; the results showed that YB-1 itself, iron-regulatory
      protein 2 (IRP2), and five ribosomal proteins each served as partners to YB-1. We
      then examined the biological effect of the interaction of YB-1 and IRP2 on
      translational regulation. Both in vitro binding and coimmunoprecipitation assays
      showed the direct interaction of YB-1 and IRP2 in the presence of a high
      concentration of iron. RNA gel shift assays showed that YB-1 reduced the
      formation of the IRP2-mRNA complex when the iron-responsive element of the
      ferritin mRNA 5' untranslated region (UTR) was used as a probe. By using an in
      vitro translation assay using luciferase mRNA ligated to the ferritin mRNA 5'UTR
      as a reporter construct, we showed that both YB-1 and IRP2 inhibited the
      translation of the mRNA. However, coadministration of YB-1 and IRP2 proteins
      abrogated the inhibition of protein synthesis by each protein. An In vivo
      coimmunoprecipitation assay showed that IRP2 bound to YB-1 in the presence of
      iron and a proteasome inhibitor. The direct interaction of YB-1 and IRP2 provides
      the first evidence of the involvement of YB-1 in the translational regulation of
      an iron-related protein.

PMID- 12192039
TI  - I-mfa domain proteins interact with Axin and affect its regulation of the Wnt and
      c-Jun N-terminal kinase signaling pathways.
AB  - I-mfa has been identified as an inhibitor of myogenic basic helix-loop-helix
      transcription factors, and a related human I-mfa domain-containing protein (HIC)
      also has been identified as a protein that regulates Tat- and Tax-mediated
      expression of viral promoters. HIC and I-mfa represent a family of proteins that
      share a highly conserved cysteine-rich domain, termed the I-mfa domain. We show
      here that both I-mfa domain proteins, HIC and I-mfa, interacted in vivo with the
      Axin complex through their C-terminal I-mfa domains. This interaction inhibited
      Axin-mediated downregulation of free levels of cytosolic beta-catenin. I-mfa and
      HIC also both directly interacted with lymphocyte enhancer factor (LEF); however,
      I-mfa but not HIC significantly inhibited reporter constructs regulated by beta
      catenin. The overexpression of HIC but not I-mfa decreased the inhibitory effects
      of Axin on beta-catenin-regulated reporter constructs, while both HIC and I-mfa
      decreased Axin-mediated c-Jun N-terminal kinase (JNK) activation. These data
      reveal for the first time that I-mfa domain proteins interact with the Axin
      complex and affect Axin regulation of both the Wnt and the JNK activation
      pathways. Interestingly, HIC differs from I-mfa in that I-mfa affects both Axin
      function and T-cell factor- or LEF-regulated transcription in the Wnt signaling
      pathway while HIC affects primarily Axin function.

PMID- 12192040
TI  - Targeted histone acetylation at the yeast CUP1 promoter requires the
      transcriptional activator, the TATA boxes, and the putative histone acetylase
      encoded by SPT10.
AB  - The relationship between chromatin remodeling and histone acetylation at the
      yeast CUP1 gene was addressed. CUP1 encodes a metallothionein required for cell
      growth at high copper concentrations. Induction of CUP1 with copper resulted in
      targeted acetylation of both H3 and H4 at the CUP1 promoter. Nucleosomes
      containing upstream activating sequences and sequences farther upstream were the
      targets for H3 acetylation. Targeted acetylation of H3 and H4 required the
      transcriptional activator (Ace1p) and the TATA boxes, suggesting that targeted
      acetylation occurs when TATA-binding protein binds to the TATA box or at a later
      stage in initiation. We have shown previously that induction results in
      nucleosome repositioning over the entire CUP1 gene, which requires Ace1p but not
      the TATA boxes. Therefore, the movement of nucleosomes occurring on CUP1
      induction is independent of targeted acetylation. Targeted acetylation of both H3
      and H4 also required the product of the SPT10 gene, which encodes a putative
      histone acetylase implicated in regulation at core promoters. Disruption of SPT10
      was lethal at high copper concentrations and correlated with slower induction and
      reduced maximum levels of CUP1 mRNA. These observations constitute evidence for a
      novel mechanism of chromatin activation at CUP1, with a major role for the TATA
      box.

PMID- 12192041
TI  - Regulation of the premiddle and middle phases of expression of the NDT80 gene
      during sporulation of Saccharomyces cerevisiae.
AB  - The NDT80 gene of Saccharomyces cerevisiae, which encodes a global activator of
      transcription of middle sporulation-specific genes, is first expressed after the
      activation of early meiotic genes but prior to activation of middle sporulation
      specific genes. Both upstream repression sequence 1 (URS1) and mid-sporulation
      element (MSE) sites are present in the promoter region of the NDT80 gene; these
      elements have been shown previously to contribute to the regulation of expression
      of early and middle sporulation-specific genes, respectively, by mediating
      repression in growing cells and activation at specific times during sporulation.
      In this study, we have shown that the overlapping windows of URS1- and MSE
      mediated repression and activation are responsible for the distinctive premiddle
      expression pattern of the NDT80 gene. Our data suggest that a Sum1-associated
      repression complex bound at the NDT80 MSE sites prevents Ime1 tethered at the
      NDT80 URS1 sites from activating transcription of the NDT80 gene at the time that
      Ime1-dependent activation of early URS1-regulated meiotic genes is occurring. We
      propose that a decrease in the efficiency of Sum1-mediated repression as cells
      progress through the early events of the sporulation program allows the
      previously inactive Ime1 tethered at the URS1(NDT80) sites to promote a low level
      of expression of the NDT80 gene. This initial phase of URS1-dependent NDT80
      expression is followed by Ndt80-dependent upregulation of its own expression,
      which requires the MSE(NDT80) sites and occurs concomitantly with Ndt80-dependent
      activation of a set of middle MSE-regulated sporulation-specific genes. Mutation
      of IME2 prevents expression of NDT80 in sporulating cells. We show in this study
      that NDT80 is expressed and that middle genes are activated in cells of an
      Deltaime2/Deltaime2 Deltasum1/Deltasum1 strain in sporulation medium. This
      suggests that Ime2 activates expression of NDT80 by eliminating Sum1-mediated
      repression.

PMID- 12192042
TI  - Role of Ndt80, Sum1, and Swe1 as targets of the meiotic recombination checkpoint
      that control exit from pachytene and spore formation in Saccharomyces cerevisiae.
AB  - The meiotic recombination checkpoint, which is triggered by defects in
      recombination or chromosome synapsis, arrests sporulating cells of Saccharomyces
      cerevisiae at pachytene by preventing accumulation of active Clb-Cdc28. We
      compared the effects of manipulating the three known targets of the meiotic
      recombination checkpoint, NDT80, SWE1, and SUM1, in dmc1-arrested cells. Ndt80 is
      an activator of a set of middle sporulation-specific genes (MSGs), which includes
      CLB genes and genes involved in spore wall formation; Swe1 inhibits Clb-Cdc28
      activity; and Sum1 is a repressor of NDT80 and some MSGs. Activation of the
      checkpoint leads to inhibition of Ndt80 activity and to stabilization of Swe1 and
      Sum1. Thus, dmc1-arrested cells fail to express MSGs, arrest at pachytene, and do
      not form spores. Our study shows that dmc1/dmc1 sum1/sum1 cells expressed MSGs
      prematurely and at high levels, entered the meiotic divisions efficiently, and in
      some cases formed asci containing mature spores. In contrast, dmc1/dmc1 swe1/swe1
      cells expressed MSGs at a very low level, were inefficient and delayed in entry
      into the meiotic divisions, and never formed mature spores. We found that cells
      of dmc1/dmc1 sum1/sum1 ndt80/ndt80 and dmc1/dmc1 swe1/swe1 ndt80/ndt80 strains
      arrested at pachytene and that dmc1/dmc1 or dmc1/dmc1 swe1/swe1 cells
      overexpressing NDT80 were less efficient in bypassing checkpoint-mediated arrest
      than dmc1/dmc1 sum1/sum1 cells. Our results are consistent with previous
      suggestions that increased Clb-Cdc28 activity, caused by mutation of SWE1 or by
      an NDT80-dependent increase in CLB expression, allows dmc1/dmc1 cells to exit
      pachytene and that subsequent upregulation of Ndt80 activity by a feedback
      mechanism promotes entry into the meiotic divisions. Spore morphogenesis,
      however, requires efficient and timely activation of MSGs, which we speculate was
      achieved in dmc1/dmc1 sum1/sum1 cells by premature expression of NDT80.

PMID- 12192044
TI  - Targeted recruitment of Rpd3 histone deacetylase represses transcription by
      inhibiting recruitment of Swi/Snf, SAGA, and TATA binding protein.
AB  - Certain DNA-binding repressors inhibit transcription by recruiting Rpd3 histone
      deacetylase complexes to promoters and generating domains of histone
      deacetylation that extend over a limited number of nucleosomes. Here, we show
      that the degree of Rpd3-dependent repression depends on the activator and the
      level of activation, not the extent of histone deacetylation. In all cases
      tested, activator binding is unaffected by histone deacetylation. In contrast,
      Rpd3-dependent repression is associated with decreased occupancy by TATA binding
      protein (TBP), the Swi/Snf nucleosome-remodeling complex, and the SAGA histone
      acetylase complex. Transcriptional repression is bypassed by direct recruitment
      of TBP and several TBP-associated factors, but not by natural activation domains
      or direct recruitment of polymerase II holoenzyme components. These results
      suggest that the domain of localized histone deacetylation generated by
      recruitment of Rpd3 mediates repression by inhibiting recruitment of chromatin
      modifying activities and TBP.

PMID- 12192043
TI  - Coupling of termination, 3' processing, and mRNA export.
AB  - In a screen to identify genes required for mRNA export in Saccharomyces
      cerevisiae, we isolated an allele of poly(A) polymerase (PAP1) and novel alleles
      encoding several other 3' processing factors. Many newly isolated and some
      previously described mutants (rna14-48, rna14-49, rna14-64, rna15-58, and pcf11-1
      strains) are defective in polymerase II (Pol II) termination but, interestingly,
      retain the ability to polyadenylate these improperly processed transcripts at the
      nonpermissive temperature. Deletion of the cis-acting sequences required to
      couple 3' processing and termination also produces transcripts that fail to exit
      the nucleus, suggesting that all of these processes (cleavage, termination, and
      export) are coupled. We also find that several but not all mRNA export mutants
      produce improperly 3' processed transcripts at the nonpermissive temperature. 3'
      maturation defects in mRNA export mutants include improper Pol II termination
      and/or the previously characterized hyperpolyadenylation of transcripts.
      Importantly, not all mRNA export mutants have defects in 3' processing. The
      similarity of the phenotypes of some mRNA export mutants and 3' processing
      mutants indicates that some factors from each process may mechanistically
      interact to couple mRNA processing and export. Consistent with this assumption,
      we present evidence that Xpo1p interacts in vivo with several 3' processing
      factors and that the addition of recombinant Xpo1p to in vitro processing
      reaction mixtures stimulates 3' maturation. Of the core 3' processing factors
      tested (Rna14p, Rna15p, Pcf11p, Hrp1p, Fip1p, and Cft1p), only Hrp1p shuttles.
      Overexpression of Rat8p/Dbp5p suppresses both 3' processing and mRNA export
      defects found in xpo1-1 cells.

PMID- 12192045
TI  - Maximal induction of a subset of interferon target genes requires the chromatin
      remodeling activity of the BAF complex.
AB  - The mammalian SWI/SNF-like chromatin-remodeling BAF complex plays several
      important roles in controlling cell proliferation and differentiation.
      Interferons (IFNs) are key mediators of cellular antiviral and antiproliferative
      activities. In this report, we demonstrate that the BAF complex is required for
      the maximal induction of a subset of IFN target genes by alpha IFN (IFN-alpha).
      The BAF complex is constitutively associated with the IFITM3 promoter in vivo and
      facilitates the chromatin remodeling of the promoter upon IFN-alpha induction.
      Furthermore, we show that the ubiquitous transcription activator Sp1 interacts
      with the BAF complex in vivo and augments the BAF-mediated activation of the
      IFITM3 promoter. Sp1 binds constitutively to the IFITM3 promoter in the absence
      of the BAF complex, suggesting that it may recruit and/or stabilize the BAF
      complex binding to the IFITM3 promoter. Our results bring new mechanistic
      insights into the antiproliferative effects of the chromatin-remodeling BAF
      complex.

PMID- 12192046
TI  - Stimulation of 3'-->5' exonuclease and 3'-phosphodiesterase activities of yeast
      apn2 by proliferating cell nuclear antigen.
AB  - The Apn2 protein of Saccharomyces cerevisiae contains 3'-->5' exonuclease and 3'
      phosphodiesterase activities, and these activities function in the repair of DNA
      strand breaks that have 3'-damaged termini and which are formed in DNA by the
      action of oxygen-free radicals. Apn2 also has an AP endonuclease activity and
      functions in the removal of abasic sites from DNA. Here, we provide evidence for
      the physical and functional interaction of Apn2 with proliferating cell nuclear
      antigen (PCNA). As indicated by gel filtration and two-hybrid studies, Apn2
      interacts with PCNA both in vitro and in vivo and mutations in the consensus PCNA
      binding motif of Apn2 abolish this interaction. Importantly, PCNA stimulates the
      3'-->5' exonuclease and 3'-phosphodiesterase activities of Apn2. We have examined
      the involvement of the interdomain connector loop (IDCL) and of the carboxy
      terminal domain of PCNA in Apn2 binding and found that Apn2 binds PCNA via
      distinct domains dependent upon whether the binding is in the absence or presence
      of DNA. In the absence of DNA, Apn2 binds PCNA through its IDCL domain, whereas
      in the presence of DNA, when PCNA has been loaded onto the template-primer
      junction by replication factor C, the C-terminal domain of PCNA mediates the
      binding.

PMID- 12192047
TI  - Rab3D is not required for exocrine exocytosis but for maintenance of normally
      sized secretory granules.
AB  - Rab3D, a member of the Rab3 subfamily of the Rab/ypt GTPases, is expressed on
      zymogen granules in the pancreas as well as on secretory vesicles in mast cells
      and in the parotid gland. To shed light on the function of Rab3D, we have
      generated Rab3D-deficient mice. These mice are viable and have no obvious
      phenotypic changes. Secretion of mast cells is normal as revealed by capacitance
      patch clamping. Furthermore, enzyme content and overall morphology are unchanged
      in pancreatic and parotid acinar cells of knockout mice. Both the exocrine
      pancreas and the parotid gland show normal release kinetics in response to
      secretagogue stimulation, suggesting that Rab3D is not involved in exocytosis.
      However, the size of secretory granules in both the exocrine pancreas and the
      parotid gland is significantly increased, with the volume being doubled. We
      conclude that Rab3D exerts its function during granule maturation, possibly by
      preventing homotypic fusion of secretory granules.

PMID- 12192048
TI  - Enzymes of the SUMO modification pathway localize to filaments of the nuclear
      pore complex.
AB  - SUMOs are small ubiquitin-related polypeptides that are reversibly conjugated to
      many nuclear proteins. Although the number of identified substrates has grown
      rapidly, relatively little is still understood about when, where, and why most
      proteins are modified by SUMO. Here, we demonstrate that enzymes involved in the
      SUMO modification and demodification of proteins are components of the nuclear
      pore complex (NPC). We show that SENP2, a SUMO protease that is able to demodify
      both SUMO-1 and SUMO-2 or SUMO-3 protein conjugates, localizes to the
      nucleoplasmic face of the NPC. The unique amino-terminal domain of SENP2
      interacts with the FG repeat domain of Nup153, indicating that SENP2 associates
      with the nucleoplasmic basket of the NPC. We also investigated the localization
      of the SUMO conjugating enzyme, Ubc9. Using immunogold labeling of isolated
      nuclear envelopes, we found that Ubc9 localizes to both the cytoplasmic and the
      nucleoplasmic filaments of the NPC. In vitro binding studies revealed that Ubc9
      and SUMO-1-modified RanGAP1 bind synergistically to form a trimeric complex with
      a component of the cytoplasmic filaments of the NPC, Nup358. Our results indicate
      that both SUMO modification and demodification of proteins may occur at the NPC
      and suggest a connection between the SUMO modification pathway and
      nucleocytoplasmic transport.

PMID- 12192049
TI  - A Mammalian bromodomain protein, brd4, interacts with replication factor C and
      inhibits progression to S phase.
AB  - Brd4 belongs to the BET family of nuclear proteins that carry two bromodomains
      implicated in the interaction with chromatin. Expression of Brd4 correlates with
      cell growth and is induced during early G(1) upon mitogenic stimuli. In the
      present study, we investigated the role of Brd4 in cell growth regulation. We
      found that ectopic expression of Brd4 in NIH 3T3 and HeLa cells inhibits cell
      cycle progression from G(1) to S. Coimmunoprecipitation experiments showed that
      endogenous and transfected Brd4 interacts with replication factor C (RFC), the
      conserved five-subunit complex essential for DNA replication. In vitro analysis
      showed that Brd4 binds directly to the largest subunit, RFC-140, thereby
      interacting with the entire RFC. In line with the inhibitory activity seen in
      vivo, recombinant Brd4 inhibited RFC-dependent DNA elongation reactions in vitro.
      Analysis of Brd4 deletion mutants indicated that both the interaction with RFC
      140 and the inhibition of entry into S phase are dependent on the second
      bromodomain of Brd4. Lastly, supporting the functional importance of this
      interaction, it was found that cotransfection with RFC-140 reduced the growth
      inhibitory effect of Brd4. Taken as a whole, the present study suggests that Brd4
      regulates cell cycle progression in part by interacting with RFC.

PMID- 12192050
TI  - Chk2 is a tumor suppressor that regulates apoptosis in both an ataxia
      telangiectasia mutated (ATM)-dependent and an ATM-independent manner.
AB  - In response to ionizing radiation (IR), the tumor suppressor p53 is stabilized
      and promotes either cell cycle arrest or apoptosis. Chk2 activated by IR
      contributes to this stabilization, possibly by direct phosphorylation. Like p53,
      Chk2 is mutated in patients with Li-Fraumeni syndrome. Since the ataxia
      telangiectasia mutated (ATM) gene is required for IR-induced activation of Chk2,
      it has been assumed that ATM and Chk2 act in a linear pathway leading to p53
      activation. To clarify the role of Chk2 in tumorigenesis, we generated gene
      targeted Chk2-deficient mice. Unlike ATM(-/-) and p53(-/-) mice, Chk2(-/-) mice
      do not spontaneously develop tumors, although Chk2 does suppress 7,12
      dimethylbenzanthracene-induced skin tumors. Tissues from Chk2(-/-) mice,
      including those from the thymus, central nervous system, fibroblasts, epidermis,
      and hair follicles, show significant defects in IR-induced apoptosis or impaired
      G(1)/S arrest. Quantitative comparison of the G(1)/S checkpoint, apoptosis, and
      expression of p53 proteins in Chk2(-/-) versus ATM(-/-) thymocytes suggested that
      Chk2 can regulate p53-dependent apoptosis in an ATM-independent manner. IR
      induced apoptosis was restored in Chk2(-/-) thymocytes by reintroduction of the
      wild-type Chk2 gene but not by a Chk2 gene in which the sites phosphorylated by
      ATM and ataxia telangiectasia and rad3(+) related (ATR) were mutated to alanine.
      ATR may thus selectively contribute to p53-mediated apoptosis. These data
      indicate that distinct pathways regulate the activation of p53 leading to cell
      cycle arrest or apoptosis.

PMID- 12192051
TI  - The SMN complex is associated with snRNPs throughout their cytoplasmic assembly
      pathway.
AB  - The common neurodegenerative disease spinal muscular atrophy is caused by reduced
      levels of the survival of motor neurons (SMN) protein. SMN associates with
      several proteins (Gemin2 to Gemin6) to form a large complex which is found both
      in the cytoplasm and in the nucleus. The SMN complex functions in the assembly
      and metabolism of several RNPs, including spliceosomal snRNPs. The snRNP core
      assembly takes place in the cytoplasm from Sm proteins and newly exported snRNAs.
      Here, we identify three distinct cytoplasmic SMN complexes, each representing a
      defined intermediate in the snRNP biogenesis pathway. We show that the SMN
      complex associates with newly exported snRNAs containing the nonphosphorylated
      form of the snRNA export factor PHAX. The second SMN complex identified contains
      assembled Sm cores and m(3)G-capped snRNAs. Finally, the SMN complex is
      associated with a preimport complex containing m(3)G-capped snRNP cores bound to
      the snRNP nuclear import mediator snurportin1. Thus, the SMN complex is
      associated with snRNPs during the entire process of their biogenesis in the
      cytoplasm and may have multiple functions throughout this process.

PMID- 12192052
TI  - MLL-AFX requires the transcriptional effector domains of AFX to transform myeloid
      progenitors and transdominantly interfere with forkhead protein function.
AB  - MLL-AFX is a fusion gene created by t(X;11) chromosomal translocations in a
      subset of acute leukemias of either myeloid or lymphoid derivation. It codes for
      a chimeric protein consisting of MLL fused to AFX, a forkhead transcription
      factor that normally regulates genes involved in apoptosis and cell cycle
      progression. We demonstrate here that forced expression of MLL-AFX enhances the
      self-renewal of hematopoietic progenitors in vitro and induces acute myeloid
      leukemias after long latencies in syngeneic recipient mice. MLL-AFX interacts
      with the transcriptional coactivator CBP, which is also a fusion partner for MLL
      in human leukemias. A potent minimal transactivation domain (CR3) at the C
      terminus of AFX mediates interactions with the KIX domain of CBP and is necessary
      for transformation of myeloid progenitors by MLL-AFX. However, CR3 alone is not
      sufficient, suggesting that simple acquisition of a transactivation domain per se
      does not activate the oncogenic potential of MLL. Rather, two conserved
      transcriptional effector domains (CR2 and CR3) of AFX are required for full
      oncogenicity of MLL-AFX and also endow it with the potential to competitively
      interfere with transcription and apoptosis mediated by wild-type forkhead
      proteins. Furthermore, a dominant-negative mutant of AFX containing CR2 and CR3
      enhances the growth of myeloid progenitors in vitro, although considerably less
      effectively than does MLL-AFX. Taken together, these data suggest that
      recruitment of transcriptional cofactors utilized by forkhead proteins is a
      critical requirement for oncogenic action of MLL-AFX, which may impact both MLL-
      and forkhead-dependent transcriptional pathways.

PMID- 12192053
TI  - Basolateral targeting of ERBB2 is dependent on a novel bipartite juxtamembrane
      sorting signal but independent of the C-terminal ERBIN-binding domain.
AB  - ERBB2 is a receptor tyrosine kinase present on the basolateral membrane of
      polarized epithelia and has important functions in organ development and
      tumorigenesis. Using mutagenic analyses and Madin-Darby canine kidney (MDCK)
      cells, we have investigated the signals that regulate basolateral targeting of
      ERBB2. We show that basolateral delivery of ERBB2 is dependent on a novel
      bipartite juxtamembrane sorting signal residing between Gln-692 and Thr-701. The
      signal shows only limited sequence homology to known basolateral targeting
      signals and is both necessary and sufficient for correct sorting of ERBB2. In
      addition we demonstrate that this motif can function as a dominant basolateral
      targeting signal by its ability to redirect the apically localized P75
      neurotrophin receptor to the basolateral membrane domain of polarized epithelial
      cells. Interestingly, LLC-PK1 cells, which are deficient for the micro 1B subunit
      of the AP1B adaptor complex, missort a large proportion of ERBB2 to the apical
      membrane domain. This missorting can be partially corrected by the introduction
      of micro 1B, suggesting a possible role for AP1B in ERBB2 endosomal trafficking.
      Furthermore, we find that the C-terminal ERBIN binding domain of ERBB2 is not
      necessary for its basolateral targeting in MDCK cells.

PMID- 12192054
TI  - Redundant role of tissue-selective TAF(II)105 in B lymphocytes.
AB  - Regulated gene expression is a complex process achieved through the function of
      multiple protein factors acting in concert at a given promoter. The transcription
      factor TFIID is a central component of the machinery regulating mRNA synthesis by
      RNA polymerase II. This large multiprotein complex is composed of the TATA box
      binding protein (TBP) and several TBP-associated factors (TAF(II)s). The recent
      discovery of multiple TBP-related factors and tissue-specific TAF(II)s suggests
      the existence of specialized TFIID complexes that likely play a critical role in
      regulating transcription in a gene- and tissue-specific manner. The tissue
      selective factor TAF(II)105 was originally identified as a component of TFIID
      derived from a human B-cell line. In this report we demonstrate the specific
      induction of TAF(II)105 in cultured B cells in response to bacterial
      lipopolysaccharide (LPS). To examine the in vivo role of TAF(II)105, we have
      generated TAF(II)105-null mice by homologous recombination. Here we show that B
      lymphocyte development is largely unaffected by the absence of TAF(II)105.
      TAF(II)105-null B cells can proliferate in response to LPS, produce relatively
      normal levels of resting antibodies, and can mount an immune response by
      producing antigen-specific antibodies in response to immunization. Taken
      together, we conclude that the function of TAF(II)105 in B cells is likely
      redundant with the function of other TAF(II)105-related cellular proteins.

PMID- 12192055
TI  - The carboxyl-terminal region of IkappaB kinase gamma (IKKgamma) is required for
      full IKK activation.
AB  - IkappaB kinase gamma (IKKgamma) (also known as NEMO, Fip-3, and IKKAP-1) is the
      essential regulatory component of the IKK complex; it is required for NF-kappaB
      activation by various stimuli, including tumor necrosis factor alpha (TNF-alpha),
      interleukin 1 (IL-1), phorbol esters, lipopolysaccharides, and double-stranded
      RNA. IKKgamma is encoded by an X-linked gene, deficiencies in which may result in
      two human genetic disorders, incontinentia pigmenti (IP) and hypohidrotic
      ectodermal dysplasia with severe immunodeficiency. Subsequent to the linkage of
      IKKgamma deficiency to IP, we biochemically characterized the effects of a
      mutation occurring in an IP-affected family on IKK activity and NF-kappaB
      signaling. This particular mutation results in premature termination, such that
      the variant IKKgamma protein lacks its putative C-terminal Zn finger and, due to
      decreased mRNA stability, is underexpressed. Correspondingly, IKK and NF-kappaB
      activation by TNF-alpha and, to a lesser extent, IL-1 are reduced. Mutagenesis of
      the C-terminal region of IKKgamma was performed in an attempt to define the role
      of the putative Zn finger and other potential functional motifs in this region.
      The mutants were expressed in IKKgamma-deficient murine embryonic fibroblasts
      (MEFs) at levels comparable to those of endogenous IKKgamma in wild-type MEFs and
      were able to associate with IKKalpha and IKKbeta. Substitution of two leucines
      within a C-terminal leucine zipper motif markedly reduced IKK activation by TNF
      alpha and IL-1. Another point mutation resulting in a cysteine-to-serine
      substitution within the putative Zn finger motif affected IKK activation by TNF
      alpha but not by IL-1. These results may explain why cells that express these or
      similar mutant alleles are sensitive to TNF-alpha-induced apoptosis despite being
      able to activate NF-kappaB in response to other stimuli.

PMID- 12192056
TI  - Activation of rac and cdc42 video imaged by fluorescent resonance energy transfer
      based single-molecule probes in the membrane of living cells.
AB  - Rho family G proteins, including Rac and Cdc42, regulate a variety of cellular
      functions such as morphology, motility, and gene expression. We developed
      fluorescent resonance energy transfer-based probes which monitored the local
      balance between the activities of guanine nucleotide exchange factors and GTPase
      activating proteins for Rac1 and Cdc42 at the membrane. These probes, named
      Raichu-Rac and Raichu-Cdc42, consisted of a Cdc42- and Rac-binding domain of Pak,
      Rac1 or Cdc42, a pair of green fluorescent protein mutants, and a CAAX box of Ki
      Ras. With these probes, we video imaged the Rac and Cdc42 activities. In motile
      HT1080 cells, activities of both Rac and Cdc42 gradually increased toward the
      leading edge and decreased rapidly when cells changed direction. Under a higher
      magnification, we observed that Rac activity was highest immediately behind the
      leading edge, whereas Cdc42 activity was most prominent at the tip of the leading
      edge. Raichu-Rac and Raichu-Cdc42 were also applied to a rapid and simple assay
      for the analysis of putative guanine nucleotide exchange factors (GEFs) and
      GTPase-activating proteins (GAPs) in living cells. Among six putative GEFs and
      GAPs, we identified KIAA0362/DBS as a GEF for Rac and Cdc42, KIAA1256 as a GEF
      for Cdc42, KIAA0053 as a GAP for Rac and Cdc42, and KIAA1204 as a GAP for Cdc42.
      In conclusion, use of these single-molecule probes to determine Rac and Cdc42
      activity will accelerate the analysis of the spatiotemporal regulation of Rac and
      Cdc42 in a living cell.

PMID- 12192057
TI  - Chaperone proteins abrogate inhibition of the human papillomavirus (HPV) E1
      replicative helicase by the HPV E2 protein.
AB  - Human papillomavirus (HPV) DNA replication requires the viral origin recognition
      protein E2 and the presumptive viral replicative helicase E1. We now report for
      the first time efficient DNA unwinding by a purified HPV E1 protein. Unwinding
      depends on a supercoiled DNA substrate, topoisomerase I, single-stranded-DNA
      binding protein, and ATP, but not an origin. Electron microscopy revealed
      completely unwound molecules. Intermediates contained two single-stranded loops
      emanating from a single protein complex, suggesting a bidirectional E1 helicase
      which translocated the flanking DNA in an inward direction. We showed that E2
      protein partially inhibited DNA unwinding and that Hsp70 or Hsp40, which we
      reported previously to stimulate HPV-11 E1 binding to the origin and promote
      dihexameric E1 formation, apparently displaced E2 and abolished inhibition.
      Neither E2 nor chaperone proteins were detected in unwinding complexes. These
      results suggest that chaperones play important roles in the assembly and
      activation of a replicative helicase in higher eukaryotes. An E1 mutation in the
      ATP binding site caused deficient binding and unwinding of origin DNA, indicating
      the importance of ATP binding in efficient helicase assembly on the origin.

PMID- 12192058
TI  - Urocortin-deficient mice display normal stress-induced anxiety behavior and
      autonomic control but an impaired acoustic startle response.
AB  - Corticotropin-releasing hormone (Crh) plays an important role in modulating
      physiological and behavioral responses to stress. Its actions are mediated
      through two receptors, Crhr1 and Crhr2. Urocortin (Ucn), a Crh-related
      neuropeptide and the postulated endogenous ligand for Crhr2, is a potential
      mediator of stress responses. We generated Ucn-deficient mice using embryonic
      stem cell technology to determine its role in stress-induced behavioral and
      autonomic responses. Unlike Crhr1- or Crhr2-deficient mice, Ucn-deficient mice
      exhibit normal anxiety-like behavior as well as autonomic regulation in response
      to stress. However, the mutant mice display an impaired acoustic startle response
      that is not due to an obvious hearing defect. Thus, our results suggest that Ucn
      does not play an essential role in stress-induced behavioral and autonomic
      responses. Ucn may modulate the acoustic startle response through the Ucn
      expressing neuron projections from the region of the Edinger-Westphal nucleus.

PMID- 12192059
TI  - Microtubule-dependent subcellular redistribution of the transcriptional
      coactivator p/CIP.
AB  - The transcriptional coactivator p/CIP is a member of a family of nuclear receptor
      coactivator/steroid receptor coactivator (NCoA/SRC) proteins that mediate the
      transcriptional activities of nuclear hormone receptors. We have found that p/CIP
      is predominantly cytoplasmic in a large proportion of cells in various tissues of
      the developing mouse and in a number of established cell lines. In mouse
      embryonic fibroblasts, serum deprivation results in the redistribution of p/CIP
      to the cytoplasmic compartment and stimulation with growth factors or tumor
      promoting phorbol esters promotes p/CIP shuttling into the nucleus. Cytoplasmic
      accumulation of p/CIP is also cell cycle dependent, occurring predominantly
      during the S and late M phases. Leptomycin B (LMB) treatment results in a marked
      nuclear accumulation, suggesting that p/CIP undergoes dynamic nuclear export as
      well as import. We have identified a strong nuclear import signal in the N
      terminus of p/CIP and two leucine-rich motifs in the C terminus that resemble CRM
      1-dependent nuclear export sequences. When fused to green fluorescent protein,
      the nuclear export sequence region is cytoplasmic and is retained in the nucleus
      in an LMB-dependent manner. Disruption of the leucine-rich motifs prevents
      cytoplasmic accumulation. Furthermore, we demonstrate that cytoplasmic p/CIP
      associates with tubulin and that an intact microtubule network is required for
      intracellular shuttling of p/CIP. Immunoaffinity purification of p/CIP from
      nuclear and cytosolic extracts revealed that only nuclear p/CIP complexes possess
      histone acetyltransferase activity. Collectively, these results suggest that
      cellular compartmentalization of NCoA/SRC proteins could potentially regulate
      nuclear hormone receptor-mediated events as well as integrating signals in
      response to different environmental cues.

PMID- 12192060
TI  - Chondromodulin I is dispensable during enchondral ossification and eye
      development.
AB  - Chondromodulin I (chm-I), a type II transmembrane protein, is highly expressed in
      the avascular zones of cartilage but is downregulated in the hypertrophic region,
      which is invaded by blood vessels during enchondral ossification. In vitro and in
      vivo assays with the purified protein have shown chondrocyte-modulating and
      angiogenesis-inhibiting functions. To investigate chm-I function in vivo, we
      generated transgenic mice lacking chm-I mRNA and protein. Null mice are viable
      and fertile and show no morphological changes. No abnormalities in vascular
      invasion and cartilage development were detectable. No evidence was found for a
      compensating function of tendin, a recently published homologue highly expressed
      in tendons and also, at low levels, in cartilage. Furthermore, no differences in
      the expression of other angiogenic or antiangiogenic factors such as transforming
      growth factor beta1 (TGF-beta1), TGF-beta2, TGF-beta3, fibroblast growth factor
      2, and vascular endothelial growth factor were found. The surprising lack of
      phenotype in the chm-I-deficient mice suggests either a different function for
      chm-I in vivo than has been proposed or compensatory changes in uninvestigated
      angiogenic or angiogenesis-inhibiting factors. Further analysis using double
      knockout technology will be necessary to analyze the function of chm-I in the
      complex process of enchondral ossification.

PMID- 12192061
TI  - Dyrk1A haploinsufficiency affects viability and causes developmental delay and
      abnormal brain morphology in mice.
AB  - DYRK1A is the human orthologue of the Drosophila minibrain (mnb) gene, which is
      involved in postembryonic neurogenesis in flies. Because of its mapping position
      on chromosome 21 and the neurobehavioral alterations shown by mice overexpressing
      this gene, involvement of DYRK1A in some of the neurological defects of Down
      syndrome patients has been suggested. To gain insight into its physiological
      role, we have generated mice deficient in Dyrk1A function by gene targeting.
      Dyrk1A(-/-) null mutants presented a general growth delay and died during
      midgestation. Mice heterozygous for the mutation (Dyrk1A(+/-)) showed decreased
      neonatal viability and a significant body size reduction from birth to adulthood.
      General neurobehavioral analysis revealed preweaning developmental delay of
      Dyrk1A(+/-) mice and specific alterations in adults. Brains of Dyrk1A(+/-) mice
      were decreased in size in a region-specific manner, although the cytoarchitecture
      and neuronal components in most areas were not altered. Cell counts showed
      increased neuronal densities in some brain regions and a specific decrease in the
      number of neurons in the superior colliculus, which exhibited a significant size
      reduction. These data provide evidence about the nonredundant, vital role of
      Dyrk1A and suggest a conserved mode of action that determines normal growth and
      brain size in both mice and flies.

PMID- 12192063
TI  - Modern analytical ultracentrifugation in protein science: a tutorial review.
AB  - Analytical ultracentrifugation (AU) is reemerging as a versatile tool for the
      study of proteins. Monitoring the sedimentation of macromolecules in the
      centrifugal field allows their hydrodynamic and thermodynamic characterization in
      solution, without interaction with any matrix or surface. The combination of new
      instrumentation and powerful computational software for data analysis has led to
      major advances in the characterization of proteins and protein complexes. The
      pace of new advancements makes it difficult for protein scientists to gain
      sufficient expertise to apply modern AU to their research problems. To address
      this problem, this review builds from the basic concepts to advanced approaches
      for the characterization of protein systems, and key computational and internet
      resources are provided. We will first explore the characterization of proteins by
      sedimentation velocity (SV). Determination of sedimentation coefficients allows
      for the modeling of the hydrodynamic shape of proteins and protein complexes. The
      computational treatment of SV data to resolve sedimenting components has been
      achieved. Hence, SV can be very useful in the identification of the oligomeric
      state and the stoichiometry of heterogeneous interactions. The second major part
      of the review covers sedimentation equilibrium (SE) of proteins, including
      membrane proteins and glycoproteins. This is the method of choice for molar mass
      determinations and the study of self-association and heterogeneous interactions,
      such as protein-protein, protein-nucleic acid, and protein-small molecule
      binding.

PMID- 12192062
TI  - 3' end processing of Drosophila melanogaster histone pre-mRNAs: requirement for
      phosphorylated Drosophila stem-loop binding protein and coevolution of the
      histone pre-mRNA processing system.
AB  - Synthetic pre-mRNAs containing the processing signals encoded by Drosophila
      melanogaster histone genes undergo efficient and faithful endonucleolytic
      cleavage in nuclear extracts prepared from Drosophila cultured cells and 0- to 13
      h-old embryos. Biochemical requirements for the in vitro cleavage are similar to
      those previously described for the 3' end processing of mammalian histone pre
      mRNAs. Drosophila 3' end processing does not require ATP and occurs in the
      presence of EDTA. However, in contrast to mammalian processing, Drosophila
      processing generates the final product ending four nucleotides after the stem
      loop. Cleavage of the Drosophila substrates is abolished by depleting the extract
      of the Drosophila stem-loop binding protein (dSLBP), indicating that both dSLBP
      and the stem-loop structure in histone pre-mRNA are essential components of the
      processing machinery. Recombinant dSLBP expressed in insect cells by using the
      baculovirus system efficiently complements the depleted extract. Only the RNA
      binding domain plus the 17 amino acids at the C terminus of dSLBP are required
      for processing. The full-length dSLBP expressed in insect cells is quantitatively
      phosphorylated on four residues in the C-terminal region. Dephosphorylation of
      the recombinant dSLBP reduces processing activity. Human and Drosophila SLBPs are
      not interchangeable and strongly inhibit processing in the heterologous extracts.
      The RNA-binding domain of the dSLBP does not substitute for the RNA-binding
      domain of the human SLBP in histone pre-mRNA processing in mammalian extracts. In
      addition to the stem-loop structure and dSLBP, 3' processing in Drosophila
      nuclear extracts depends on the presence of a short stretch of purines located
      ca. 20 nucleotides downstream from the stem, and an Sm-reactive factor, most
      likely the Drosophila counterpart of vertebrate U7 snRNP.

PMID- 12192064
TI  - Structural and dynamic properties of water around acetylcholinesterase.
AB  - Structural and dynamic properties of water molecules around acetylcholinesterase
      are examined from a 10-nsec molecular dynamics simulation to help understand how
      the protein alters water properties. Water structure is broken down into
      hydration sites constructed from the water density <3.6 A from the protein
      surface. These sites are characterized according to occupancy, number of water
      neighbors, hydrogen bonds, dipole moment, and residence time. The site
      description provides a convenient means to describe the extent and localization
      of these properties. Determining the network of paths that waters follow from
      site to site and measuring the rate of flow of waters from the sites to the bulk
      make it possible to quantitatively study the time scales and paths that water
      molecules follow as they move around the protein.

PMID- 12192065
TI  - Interdomain engineered disulfide bond permitting elucidation of mechanisms of
      inactivation of coagulation factor Va by activated protein C.
AB  - Procoagulant factor Va (FVa) is inactivated via limited proteolysis at three Arg
      residues in the A2 domain by the anticoagulant serine protease, activated protein
      C (APC). Cleavage by APC at Arg306 in FVa causes dissociation of the A2 domain
      from the heterotrimeric A1:A2:A3 structure and complete loss of procoagulant
      activity. To help distinguish inactivation mechanisms involving A2 domain
      dissociation from inactivation mechanisms involving unfavorable changes in factor
      Xa (FXa) affinity, we used our FVa homology model to engineer recombinant FVa
      mutants containing an interdomain disulfide bond (Cys609-Cys1691) between the A2
      and A3 domains (A2-SS-A3 mutants) in addition to cleavage site mutations,
      Arg506Gln and Arg679Gln. SDS-PAGE analysis showed that the disulfide bond in A2
      SS-A3 mutants prevented dissociation of the A2 domain. In the absence of A2
      domain dissociation from the A1:A2:A3 trimer, APC cleavage at Arg306 alone caused
      a sevenfold decrease in affinity for FXa, whereas APC cleavages at Arg306,
      Arg506, and Arg679 caused a 70-fold decrease in affinity for FXa and a 10-fold
      decrease in the k(cat) of the prothrombinase complex for prothrombin without any
      effect on the apparent K(m) for prothrombin. Therefore, for FVa inactivation by
      APC, dissociation of the A2 domain may provide only a modest final step, whereas
      the critical events are the cleavages at Arg506 and Arg306, which effectively
      inactivate FVa before A2 dissociation can take place. Nonetheless, for FVa Leiden
      (Gln506-FVa) inactivation by APC, A2 domain dissociation may become
      mechanistically important, depending on the ambient FXa concentration.

PMID- 12192066
TI  - The effect of prime-site occupancy on the hepatitis C virus NS3 protease
      structure.
AB  - We recently reported a new class of inhibitors of the chymotrypsin-like serine
      protease NS3 of the hepatitis C virus. These inhibitors exploit the binding
      potential of the S' site of the protease, which is not generally used by the
      natural substrates. The effect of prime-site occupancy was analyzed by circular
      dichroism spectroscopy and limited proteolysis-mass spectrometry. Generally,
      nonprime inhibitors cause a structural change in NS3. Binding in the S' site
      produces additional conformational changes with different binding modes, even in
      the case of the NS3/4A cofactor complex. Notably, inhibitor binding either in the
      S or S' site also has profound effects on the stabilization of the protease. In
      addition, the stabilization propagates to regions not in direct contact with the
      inhibitor. In particular, the N-terminal region, which according to structural
      studies is endowed with low structural stability and is not stabilized by
      nonprime inhibitors, was now fully protected from proteolytic degradation. From
      the perspective of drug design, P-P' inhibitors take advantage of binding
      pockets, which are not exploited by the natural HCV substrates; hence, they are
      an entry point for a novel class of NS3/4A inhibitors. Here we show that binding
      of each inhibitor is associated with a specific structural rearrangement. The
      development of a range of inhibitors belonging to different classes and an
      understanding of their interactions with the protease are required to address the
      issue of the most likely outcome of viral protease inhibitor therapy, that is,
      viral resistance.

PMID- 12192067
TI  - Hydrogen/deuterium exchange and mass spectrometric analysis of a protein
      containing multiple disulfide bonds: Solution structure of recombinant macrophage
      colony stimulating factor-beta (rhM-CSFbeta).
AB  - Studies with the homodimeric recombinant human macrophage colony-stimulating
      factor beta (rhM-CSFbeta), show for the first time that a large number (9) of
      disulfide linkages can be reduced after amide hydrogen/deuterium (H/D) exchange,
      and the protein digested and analyzed successfully for the isotopic composition
      by electrospray mass spectrometry. Analysis of amide H/D after exchange-in shows
      that in solution the conserved four-helix bundle of (rhM-CSFbeta) has fast and
      moderately fast exchangeable sections of amide hydrogens in the alphaA helix, and
      mostly slow exchanging sections of amide hydrogens in the alphaB, alphaC, and
      alphaD helices. Most of the amide hydrogens in the loop between the beta1 and
      beta4 sheets exhibited fast or moderately fast exchange, whereas in the amino
      acid 63-67 loop, located at the interface of the two subunits, the exchange was
      slow. Solvent accessibility as measured by H/D exchange showed a better
      correlation with the average depth of amide residues calculated from reported X
      ray crystallographic data for rhM-CSFalpha than with the average B-factor. The
      rates of H/D exchange in rhM-CSFbeta appear to correlate well with the exposed
      surface calculated for each amino acid residue in the crystal structure except
      for the alphaD helix. Fast hydrogen isotope exchange throughout the segment amino
      acids 150-221 present in rhM-CSFbeta, but not rhM-CSFalpha, provides evidence
      that the carboxy-terminal region is unstructured. It is, therefore, proposed that
      the anomalous behavior of the alphaD helix is due to interaction of the carboxy
      terminal tail with this helical segment.

PMID- 12192070
TI  - Characterization and multiple molecular forms of TorD from Shewanella massilia,
      the putative chaperone of the molybdoenzyme TorA.
AB  - Several bacteria use trimethylamine N-oxyde (TMAO) as an exogenous electron
      acceptor for anaerobic respiration. This metabolic pathway involves expression of
      the tor operon that codes for a periplasmic molybdopterin-containing reductase of
      the DMSO/TMAO family, a pentahemic c-type cytochrome, and the TorD cytoplasmic
      chaperone, possibly required for acquisition of the molybdenum cofactor and
      translocation of the reductase by the twin-arginine translocation system. In this
      report, we show that the TorD chaperone from Shewanella massilia forms multiple
      and stable oligomeric species. The monomeric, dimeric, and trimeric forms were
      purified to homogeneity and characterized by analytical ultracentrifugation.
      Small-angle X-ray scattering (SAXS) and preliminary diffraction data indicated
      that the TorD dimer is made of identical protein modules of similar size to the
      monomeric species. Interconversion of the native oligomeric forms occurred at
      acidic pH value. In this condition, ANS fluorescence indicates a non-native
      conformation of the polypeptide chain in which, according to the circular
      dichroism spectra, the alpha-helical content is similar to that of the native
      species. Surface plasmon resonance showed that both the monomeric and dimeric
      species bind the mature TorA enzyme, but that the dimer binds its target protein
      more efficiently. The possible biologic significance of these oligomers is
      discussed in relation to the chaperone activity of TorD, and to the ability of
      another member of the TorD family to bind the Twin Arginine leader sequences of
      the precursor of DMSO/TMAO reductases.

PMID- 12192069
TI  - Active site geometry of oxalate decarboxylase from Flammulina velutipes: Role of
      histidine-coordinated manganese in substrate recognition.
AB  - Oxalate decarboxylase (OXDC) from the wood-rotting fungus Flammulina velutipes,
      which catalyzes the conversion of oxalate to formic acid and CO(2) in a single
      step reaction, is a duplicated double-domain germin family enzyme. It has
      agricultural as well as therapeutic importance. We reported earlier the
      purification and molecular cloning of OXDC. Knowledge-based modeling of the
      enzyme reveals a beta-barrel core in each of the two domains organized in the
      hexameric state. A cluster of three histidines suitably juxtaposed to coordinate
      a divalent metal ion exists in both the domains. Involvement of the two histidine
      clusters in the catalytic mechanism of the enzyme, possibly through coordination
      of a metal cofactor, has been hypothesized because all histidine knockout mutants
      showed total loss of decarboxylase activity. The atomic absorption spectroscopy
      analysis showed that OXDC contains Mn(2+) at up to 2.5 atoms per subunit. Docking
      of the oxalate in the active site indicates a similar electrostatic environment
      around the substrate-binding site in the two domains. We suggest that the
      histidine coordinated manganese is critical for substrate recognition and is
      directly involved in the catalysis of the enzyme.

PMID- 12192068
TI  - A structurally conserved water molecule in Rossmann dinucleotide-binding domains.
AB  - A computational comparison of 102 high-resolution (</=1.90 A) enzyme-dinucleotide
      (NAD, NADP, FAD) complexes was performed to investigate the role of solvent in
      dinucleotide recognition by Rossmann fold domains. The typical binding site
      contains about 9-12 water molecules, and about 30% of the hydrogen bonds between
      the protein and the dinucleotide are water mediated. Detailed inspection of the
      structures reveals a structurally conserved water molecule bridging dinucleotides
      with the well-known glycine-rich phosphate-binding loop. This water molecule
      displays a conserved hydrogen-bonding pattern. It forms hydrogen bonds to the
      dinucleotide pyrophosphate, two of the three conserved glycine residues of the
      phosphate-binding loop, and a residue at the C-terminus of strand four of the
      Rossmann fold. The conserved water molecule is also present in high-resolution
      structures of apo enzymes. However, the water molecule is not present in
      structures displaying significant deviations from the classic Rossmann fold
      motif, such as having nonstandard topology, containing a very short phosphate
      binding loop, or having alpha-helix "A" oriented perpendicular to the beta-sheet.
      Thus, the conserved water molecule appears to be an inherent structural feature
      of the classic Rossmann dinucleotide-binding domain.

PMID- 12192072
TI  - Crystal structures and enzymatic properties of three formyltransferases from
      archaea: environmental adaptation and evolutionary relationship.
AB  - Formyltransferase catalyzes the reversible formation of formylmethanofuran from
      N(5)-formyltetrahydromethanopterin and methanofuran, a reaction involved in the
      C1 metabolism of methanogenic and sulfate-reducing archaea. The crystal structure
      of the homotetrameric enzyme from Methanopyrus kandleri (growth temperature
      optimum 98 degrees C) has recently been solved at 1.65 A resolution. We report
      here the crystal structures of the formyltransferase from Methanosarcina barkeri
      (growth temperature optimum 37 degrees C) and from Archaeoglobus fulgidus (growth
      temperature optimum 83 degrees C) at 1.9 A and 2.0 A resolution, respectively.
      Comparison of the structures of the three enzymes revealed very similar folds.
      The most striking difference found was the negative surface charge, which was -32
      for the M. kandleri enzyme, only -8 for the M. barkeri enzyme, and -11 for the A.
      fulgidus enzyme. The hydrophobic surface fraction was 50% for the M. kandleri
      enzyme, 56% for the M. barkeri enzyme, and 57% for the A. fulgidus enzyme. These
      differences most likely reflect the adaptation of the enzyme to different
      cytoplasmic concentrations of potassium cyclic 2,3-diphosphoglycerate, which are
      very high in M. kandleri (>1 M) and relatively low in M. barkeri and A. fulgidus.
      Formyltransferase is in a monomer/dimer/tetramer equilibrium that is dependent on
      the salt concentration. Only the dimers and tetramers are active, and only the
      tetramers are thermostable. The enzyme from M. kandleri is a tetramer, which is
      active and thermostable only at high concentrations of potassium phosphate (>1 M)
      or potassium cyclic 2,3-diphosphoglycerate. Conversely, the enzyme from M.
      barkeri and A. fulgidus already showed these properties, activity and stability,
      at much lower concentrations of these strong salting-out salts.

PMID- 12192071
TI  - Plasticity in structure and interactions is critical for the action of
      indolicidin, an antibacterial peptide of innate immune origin.
AB  - The comparative analysis of two cationic antibacterial peptides of the
      cathelicidin family-indolicidin and tritrypticin-enabled addressing the
      structural features critical for the mechanism of indolicidin activity.
      Functional behavior of retro-indolicidin was found to be identical to that of
      native indolicidin. It is apparent that the gross conformational propensities
      associated with retro-peptides resemble those of the native sequences, suggesting
      that native and retro-peptides can have similar structures. Both the native and
      the retro-indolicidin show identical affinities while binding to endotoxin, the
      initial event associated with the antibacterial activity of cationic peptide
      antibiotics. The indolicidin-endotoxin binding was modeled by docking the
      indolicidin molecule in the endotoxin structure. The conformational flexibility
      associated with the indolicidin residues, as well as that of the fatty acid
      chains of endotoxin combined with the relatively strong structural interactions,
      such as ionic and hydrophobic, provide the basis for the endotoxin-peptide
      recognition. Thus, the key feature of the recognition between the cationic
      antibacterial peptides and endotoxin is the plasticity of molecular interactions,
      which may have been designed for the purpose of maintaining activity against a
      broad range of organisms, a hallmark of primitive host defense.

PMID- 12192073
TI  - Versatile cloning system for construction of multimeric proteins for use in
      atomic force microscopy.
AB  - This manuscript introduces a versatile system for construction of multimeric
      proteins to be used as substrates for atomic force microscopy. The construction
      makes use of a cassette system that allows modules to be cut and ligated in any
      combination in eight different positions. The modules can be sequenced in situ
      after construction. A three-module fragment can be produced that is of a size
      amenable to structural and biophysical analysis to check the effect of placing a
      protein into a multimeric construct. We show that if the parent titin modules are
      retained in a construct, they can act both as linkers and as an internal standard
      for the force measurements. Proteins that cannot be expressed solubly in an eight
      module homopolymer have been expressed and subject to force measurements using
      this system.

PMID- 12192074
TI  - Crystal structures of a meta-cleavage product hydrolase from Pseudomonas
      fluorescens IP01 (CumD) complexed with cleavage products.
AB  - 2-Hydroxy-6-oxo-7-methylocta-2,4-dienoate hydrolase (CumD) from Pseudomonas
      fluorescens IP01 hydrolyzes a meta-cleavage product generated in the cumene
      (isopropylbenzene) degradation pathway. The crystal structures of the inactive
      S103A mutant of the CumD enzyme complexed with isobutyrate and acetate ions were
      determined at 1.6 and 2.0 A resolution, respectively. The isobutyrate and acetate
      ions were located at the same position in the active site, and occupied the site
      for a part of the hydrolysis product with CumD, which has the key determinant
      group for the substrate specificity of related hydrolases. One of the oxygen
      atoms of the carboxyl group of the isobutyrate ion was hydrogen bonded with a
      water molecule and His252. Another oxygen atom of the carboxyl group was situated
      in an oxyanion hole formed by the two main-chain N atoms. The isopropyl group of
      the isobutyric acid was recognized by the side-chains of the hydrophobic
      residues. The substrate-binding pocket of CumD was long, and the inhibition
      constants of various organic acids corresponded well to it. In comparison with
      the structure of BphD from Rhodococcus sp. RHA1, the structural basis for the
      substrate specificity of related hydrolases, is revealed.

PMID- 12192075
TI  - The beta-barrel finder (BBF) program, allowing identification of outer membrane
      beta-barrel proteins encoded within prokaryotic genomes.
AB  - Many outer membrane proteins (OMPs) in Gram-negative bacteria possess known beta
      barrel three-dimensional (3D) structures. These proteins, including channel
      forming transmembrane porins, are diverse in sequence but exhibit common
      structural features. We here report computational analyses of six outer membrane
      proteins of known 3D structures with respect to (1) secondary structure, (2)
      hydropathy, and (3) amphipathicity. Using these characteristics, as well as the
      presence of an N-terminal targeting sequence, a program was developed allowing
      prediction of integral membrane beta-barrel proteins encoded within any
      completely sequenced prokaryotic genome. This program, termed the beta-barrel
      finder (BBF) program, was used to analyze the proteins encoded within the
      Escherichia coli genome. Out of 4290 sequences examined, 118 (2.8%) were
      retrieved. Of these, almost all known outer membrane proteins with established
      beta-barrel structures as well as many probable outer membrane proteins were
      identified. This program should be useful for predicting the occurrence of outer
      membrane proteins in bacteria with completely sequenced genomes.

PMID- 12192076
TI  - Impact of domain interchange on conformational stability and equilibrium folding
      of chimeric class micro glutathione transferases.
AB  - Rat micro class glutathione transferases M1-1 and M2-2 are homodimers that share
      a 78% sequence identity but display differences in stability. M1-1 is more stable
      at the secondary and tertiary structural levels, whereas its quaternary structure
      is less stable. Each subunit in these proteins consists of two structurally
      distinct domains with intersubunit contacts occurring between domain 1 of one
      subunit and domain 2 of the other subunit. The chimeric subunit variants M(12),
      which has domain 1 of M1 and domain 2 of M2, and its complement M(21), were used
      to investigate the conformational stability of the chimeric homodimers M(12)-(12)
      and M(21)-(21) to determine the contribution of each domain toward stability.
      Exchanging entire domains between class micro GSTs is accommodated by the GST
      fold. Urea-induced equilibrium unfolding data indicate that whereas the class
      micro equilibrium unfolding mechanism (i.e., N(2) <--> 2I <--> 2U) is not
      altered, domain exchanges impact significantly on the conformational stability of
      the native dimers and monomeric folding intermediates. Data for the wild-type and
      chimeric proteins indicate that the order of stability for the native dimer
      (N(2)) is M2-2 > M(12)-(12) M1-1 approximately M(21)-(21), and that the order of
      stability of the monomeric intermediate (I) is M1 > M2 approximately M(12) >
      M(21). Interactions involving Arg 77, which is topologically conserved in GSTs,
      appear to play an important role in the stability of both the native dimeric and
      folding monomeric structures.

PMID- 12192077
TI  - The role of disulfide bond in the amyloidogenic state of beta(2)-microglobulin
      studied by heteronuclear NMR.
AB  - beta(2)-Microglobulin (beta2-m) is a major component of dialysis-related amyloid
      fibrils. Although recombinant beta2-m forms needle-like fibrils by in vitro
      extension reaction at pH 2.5, reduced beta2-m, in which the intrachain disulfide
      bond is reduced, cannot form typical fibrils. Instead, thinner and flexible
      filaments are formed, as shown by atomic force microscopy images. To clarify the
      role of the disulfide bond in amyloid fibril formation, we characterized the
      conformations of the oxidized (intact) and reduced forms of beta2-m in the acid
      denatured state at pH 2.5, as well as the native state at pH 6.5, by
      heteronuclear NMR. [(1)H]-(15)N NOE at the regions between the two cysteine
      residues (Cys25-Cys80) revealed a marked difference in the pico- and nanosecond
      time scale dynamics between that the acid-denatured oxidized and reduced states,
      with the former showing reduced mobility. Intriguingly, the secondary chemical
      shifts, DeltaCalpha, DeltaCO, and DeltaHalpha, and (3)J(HNHalpha) coupling
      constants indicated that both the oxidized and reduced beta2-m at pH 2.5 have
      marginal alpha-helical propensity at regions close to the C-terminal cysteine,
      although it is a beta-sheet protein in the native state. The results suggest that
      the reduced mobility of the denatured state is an important factor for the
      amylodogenic potential of beta2-m, and that the marginal helical propensity at
      the C-terminal regions might play a role in modifying this potential.

PMID- 12192078
TI  - alpha(1)-Proteinase inhibitor mutants with specificity for plasma kallikrein and
      C1s but not C1.
AB  - Coagulation and complement proteinases are activated in sepsis, and one approach
      to therapy is to develop proteinase inhibitors that will specifically inhibit
      these proteinases without inhibiting activated protein C, a proteinase that is
      beneficial to survival. In this study, we made mutants of the serpin alpha(1)-PI,
      designed to mimic the specificity of C1-inhibitor. The P3-P2-P1 residues of
      alpha1-PI were changed from IPM to LGR and PFR, sequences preferred by C1s and
      kallikrein, respectively. Inhibition of C1s, kallikrein, factor XIIa, and
      activated protein C was assessed by SDS-PAGE, and by determination of the k(app)
      and SI. alpha(1)-PI-LGR inhibited C1s with a rate of 7790 M(-1)s(-1), but only
      minimal inhibition of C1 in a hemolytic assay was observed. Kallikrein, factor
      XIIa, and activated protein C were inhibited with rates of 382,180 M(-1)s(-1),
      10,400 M(-1)s(-1), and 3500 M(-1)s(-1), respectively. alpha(1)-PI-PFR was a poor
      inhibitor of C1s, factor XIIa, and activated protein C, but had enhanced
      reactivity with kallikrein. Changing the P4' residue of alpha(1)-PI-LGR Pro to
      Glu reduced the activity with C1s, consistent with the idea that C1s requires
      hydrophobic residues in this region of the serpin for optimal interaction. The
      data provide insight into the requirements for kallikrein and C1s inhibition
      necessary for designing inhibitors with appropriate properties for further
      investigation as therapeutic agents.

PMID- 12192079
TI  - Mapping sequence differences between thimet oligopeptidase and neurolysin
      implicates key residues in substrate recognition.
AB  - The highly homologous endopeptidases thimet oligopeptidase and neurolysin are
      both restricted to short peptide substrates and share many of the same cleavage
      sites on bioactive and synthetic peptides. They sometimes target different sites
      on the same peptide, however, and defining the determinants of differential
      recognition will help us to understand how both enzymes specifically target a
      wide variety of cleavage site sequences. We have mapped the positions of the 224
      surface residues that differ in sequence between the two enzymes onto the surface
      of the neurolysin crystal structure. Although the deep active site channel
      accounts for about one quarter of the total surface area, only 11% of the residue
      differences map to this region. Four isolated sequence changes (R470/E469,
      R491/M490, N496/H495, and T499/R498; neurolysin residues given first) are well
      positioned to affect recognition of substrate peptides, and differences in
      cleavage site specificity can be largely rationalized on the basis of these
      changes. We also mapped the positions of three cysteine residues believed to be
      responsible for multimerization of thimet oligopeptidase, a process that
      inactivates the enzyme. These residues are clustered on the outside of one
      channel wall, where multimerization via disulfide formation is unlikely to block
      the substrate-binding site. Finally, we mapped the regulatory phosphorylation
      site in thimet oligopeptidase to a location on the outside of the molecule well
      away from the active site, which indicates this modification has an indirect
      effect on activity.

PMID- 12192080
TI  - Pheromone binding by polymorphic mouse major urinary proteins.
AB  - Mouse major urinary proteins (MUPs) have been proposed to play a role in
      regulating the release and capture of pheromones. Here, we report affinity
      measurements of five recombinant urinary MUP isoforms (MUPs-I, II, VII, VIII, and
      IX) and one recombinant nasal isoform (MUP-IV) for each of three pheromonal
      ligands, (+/-)-2-sec-butyl-4,5-dihydrothiazole (SBT), 6-hydroxy-6-methyl-3
      heptanone (HMH), and (+/-)dehydro-exo-brevicomin (DHB). Dissociation constants
      for all MUP-pheromone pairs were determined by isothermal titration calorimetry,
      and data for SBT were corroborated by measurements of intrinsic protein
      fluorescence. We also report the isolation of MUP-IV protein from mouse nasal
      extracts, in which MUP-IV mRNA has been observed previously. The affinity of each
      MUP isoform for SBT (K(d) approximately 0.04 to 0.9 micro M) is higher than that
      for DHB (K(d) approximately 26 to 58 micro M), which in turn is higher than that
      for HMH (K(d) approximately 50 to 200 micro M). Isoforms I, II, VIII, and IX show
      very similar affinities for each of the ligands. MUP-VII has approximately
      twofold higher affinity for SBT but approximately twofold lower affinity for the
      other pheromones, whereas MUP-IV has approximately 23-fold higher affinity for
      SBT and approximately fourfold lower affinity for the other pheromones. The
      variations in ligand affinities of the MUP isoforms are consistent with
      structural differences in the binding cavities of the isoforms. The data indicate
      that the concentrations of available pheromones in urine may be influenced by
      changes in the expression levels of urinary MUPs or the excretion levels of other
      MUP ligands. The variation in pheromone affinities of the urinary MUP isoforms
      provides only limited support for the proposal that MUP heterogeneity plays a
      role in regulating profiles of available pheromones. However, the binding data
      support the proposed role of nasal MUPs in sequestering pheromones and possibly
      transporting them to their receptors.

PMID- 12192081
TI  - Surface adhesion of fusion proteins containing the hydrophobins HFBI and HFBII
      from Trichoderma reesei.
AB  - Hydrophobins are surface-active proteins produced by filamentous fungi, where
      they seem to be ubiquitous. They have a variety of roles in fungal physiology
      related to surface phenomena, such as adhesion, formation of surface layers, and
      lowering of surface tension. Hydrophobins can be divided into two classes based
      on the hydropathy profile of their primary sequence. We have studied the adhesion
      behavior of two Trichoderma reesei class II hydrophobins, HFBI and HFBII, as
      isolated proteins and as fusion proteins. Both hydrophobins were produced as C
      terminal fusions to the core of the hydrolytic enzyme endoglucanase I from the
      same organism. It was shown that as a fusion partner, HFBI causes the fusion
      protein to efficiently immobilize to hydrophobic surfaces, such as silanized
      glass and Teflon. The properties of the surface-bound protein were analyzed by
      the enzymatic activity of the endoglucanase domain, by surface plasmon resonance
      (Biacore), and by a quartz crystal microbalance. We found that the HFBI fusion
      forms a tightly bound, rigid surface layer on a hydrophobic support. The HFBI
      domain also causes the fusion protein to polymerize in solution, possibly to a
      decamer. Although isolated HFBII binds efficiently to surfaces, it does not cause
      immobilization as a fusion partner, nor does it cause polymerization of the
      fusion protein in solution. The findings give new information on how hydrophobins
      function and how they can be used to immobilize fusion proteins.

PMID- 12192083
TI  - Unfolding of the loggerhead sea turtle (Caretta caretta) myoglobin: A (1)H-NMR
      and electronic absorbance study.
AB  - The effect of urea concentration on the backbone solution structure of the
      cyanide derivative of ferric Caretta caretta myoglobin (at pH 5.4) is reported.
      By addition of urea, sequential and long-range nuclear Overhauser effects (NOEs)
      are gradually lost. By using the residual NOE constraints to build the molecular
      model, a picture of the unfolding pathway was obtained. When the urea
      concentration is raised to 2.2 M, helices A and B appear largely disordered;
      helices C, D, and F loose structural constraints at 3.0 M urea. At urea
      concentration >6 M, the protein appears to be fully unfolded, including the GH
      hairpin and helix E stabilizing the prosthetic group. Reversible and cooperative
      denaturation isotherms obtained by following NOE peaks are considerably different
      from those obtained by monitoring electronic absorption changes. The reversible
      and cooperative urea-dependent folding-unfolding process of C. caretta myoglobin
      follows the minimum three-state mechanism N long left and right arrow X long left
      and right arrow D, where X represents a disordered globin structure (occurring at
      approximately 4 M urea) that still binds the heme.

PMID- 12192082
TI  - Characterization of herpes simplex virus type 1 thymidine kinase mutants
      engineered for improved ganciclovir or acyclovir activity.
AB  - Herpes Simplex Virus type 1 (HSV-1) thymidine kinase (TK) is currently the most
      widely used suicide agent for gene therapy of cancer. Tumor cells that express
      HSV-1 thymidine kinase are rendered sensitive to prodrugs due to preferential
      phosphorylation by this enzyme. Although ganciclovir (GCV) is the prodrug of
      choice for use with TK, this approach is limited in part by the toxicity of this
      prodrug. From a random mutagenesis library, seven thymidine kinase variants
      containing multiple amino acid substitutions were identified on the basis of
      activity towards ganciclovir and acyclovir based on negative selection in
      Escherichia coli. Using a novel affinity chromatography column, three mutant
      enzymes and the wild-type TK were purified to homogeneity and their kinetic
      parameters for thymidine, ganciclovir, and acyclovir determined. With ganciclovir
      as the substrate, one mutant (mutant SR39) demonstrated a 14-fold decrease in
      K(m) compared to the wild-type enzyme. The most dramatic change is displayed by
      mutant SR26, with a 124-fold decrease in K(m) with acyclovir as the substrate.
      Such new "prodrug kinases" could provide benefit to ablative gene therapy by now
      making it feasible to use the relatively nontoxic acyclovir at nanomolar
      concentrations or ganciclovir at lower, less immunosuppressive doses.

PMID- 12192084
TI  - Evidence for a susceptibility gene (SLEH1) on chromosome 11q14 for systemic lupus
      erythematosus (SLE) families with hemolytic anemia.
AB  - Hemolytic anemia is a forme fruste of systemic lupus erythematosus (SLE), being
      observed months or even years before the onset of other clinical manifestations
      in some patients. We hypothesized that hemolytic anemia in those SLE-affected
      patients would identify a group of SLE pedigrees that share a high degree of
      genetic homogeneity. From 160 multiplex SLE pedigrees, we sought evidence for
      linkage in 35 (16 African-American, 17 European-American, and 2 Hispanic) who had
      at least one SLE-affected patient with hemolytic anemia. Significant linkage was
      present at 11q14 in the 16 African-American pedigrees, yielding a maximum two
      point logarithm of odds (LOD) score of 4.5 at D11S2002. The segregation pattern
      of SLE in these African-American pedigrees suggested a dominant mode of
      inheritance and, when maximized across penetrance and disease allele frequencies,
      produced a multipoint LOD of 4.7. Multipoint analysis yielded a multipoint
      heterogeneity LOD score of 3.6 (alpha = 0.63), again with maximum LOD at
      D11S2002. Finally, markers typed 7 centimorgans to either side of D11S2002
      achieved LOD scores of 3 or better by using the maximized model, supporting
      linkage to 11q14. Clearly, pedigree ascertainment based on select clinical
      manifestations is an important tool, capable of revealing otherwise cryptic
      genetic linkages in complex genetic diseases. Thus, we show strong evidence for
      an SLE susceptibility gene, SLEH1, near D11S2002 in African-American pedigrees
      multiplex for SLE that have at least one SLE-affected patient with hemolytic
      anemia.

PMID- 12192085
TI  - Salvinorin A: a potent naturally occurring nonnitrogenous kappa opioid selective
      agonist.
AB  - Salvia divinorum, whose main active ingredient is the neoclerodane diterpene
      Salvinorin A, is a hallucinogenic plant in the mint family that has been used in
      traditional spiritual practices for its psychoactive properties by the Mazatecs
      of Oaxaca, Mexico. More recently, S. divinorum extracts and Salvinorin A have
      become more widely used in the U.S. as legal hallucinogens. We discovered that
      Salvinorin A potently and selectively inhibited (3)H-bremazocine binding to
      cloned kappa opioid receptors. Salvinorin A had no significant activity against a
      battery of 50 receptors, transporters, and ion channels and showed a distinctive
      profile compared with the prototypic hallucinogen lysergic acid diethylamide.
      Functional studies demonstrated that Salvinorin A is a potent kappa opioid
      agonist at cloned kappa opioid receptors expressed in human embryonic kidney-293
      cells and at native kappa opioid receptors expressed in guinea pig brain.
      Importantly, Salvinorin A had no actions at the 5-HT(2A) serotonin receptor, the
      principal molecular target responsible for the actions of classical
      hallucinogens. Salvinorin A thus represents, to our knowledge, the first
      naturally occurring nonnitrogenous opioid-receptor subtype-selective agonist.
      Because Salvinorin A is a psychotomimetic selective for kappa opioid receptors,
      kappa opioid-selective antagonists may represent novel psychotherapeutic
      compounds for diseases manifested by perceptual distortions (e.g., schizophrenia,
      dementia, and bipolar disorders). Additionally, these results suggest that kappa
      opioid receptors play a prominent role in the modulation of human perception.

PMID- 12192086
TI  - Inactivation of CMP-N-acetylneuraminic acid hydroxylase occurred prior to brain
      expansion during human evolution.
AB  - Humans are genetically deficient in the common mammalian sialic acid N
      glycolylneuraminic acid (Neu5Gc) because of an Alu-mediated inactivating mutation
      of the gene encoding the enzyme CMP-N-acetylneuraminic acid (CMP-Neu5Ac)
      hydroxylase (CMAH). This mutation occurred after our last common ancestor with
      bonobos and chimpanzees, and before the origin of present-day humans. Here, we
      take multiple approaches to estimate the timing of this mutation in relationship
      to human evolutionary history. First, we have developed a method to extract and
      identify sialic acids from bones and bony fossils. Two Neanderthal fossils
      studied had clearly detectable Neu5Ac but no Neu5Gc, indicating that the CMAH
      mutation predated the common ancestor of humans and the Neanderthal,
      approximately 0.5-0.6 million years ago (mya). Second, we date the insertion
      event of the inactivating human-specific sahAluY element that replaced the
      ancestral AluSq element found adjacent to exon 6 of the CMAH gene in the
      chimpanzee genome. Assuming Alu source genes based on a phylogenetic tree of
      human-specific Alu elements, we estimate the sahAluY insertion time at
      approximately 2.7 mya. Third, we apply molecular clock analysis to chimpanzee and
      other great ape CMAH genes and the corresponding human pseudogene to estimate an
      inactivation time of approximately 2.8 mya. Taken together, these studies
      indicate that the CMAH gene was inactivated shortly before the time when brain
      expansion began in humankind's ancestry, approximately 2.1-2.2 mya. In this
      regard, it is of interest that although Neu5Gc is the major sialic acid in most
      organs of the chimpanzee, its expression is selectively down-regulated in the
      brain, for as yet unknown reasons.

PMID- 12192087
TI  - Ancient mitochondrial haplotypes and evidence for intragenic recombination in a
      gynodioecious plant.
AB  - Because of their extremely low nucleotide mutation rates, plant mitochondrial
      genes are generally not expected to show variation within species. Remarkably, we
      found nine distinct cytochrome b sequence haplotypes in the gynodioecious alpine
      plant Silene acaulis, with two or more haplotypes coexisting locally in each of
      three sampled regions. Moreover, there is evidence for intragenic recombination
      in the history of the haplotype sample, implying at least transient heteroplasmy
      of mitochondrial DNA (mtDNA). Heteroplasmy might be achieved by one of two
      potential mechanisms, either continuous coexistence of subgenomic fragments in
      low stoichiometry, or occasional paternal leakage of mtDNA. On the basis of
      levels of synonymous nucleotide substitutions, the average divergence time
      between haplotypes is estimated to be at least 15 million years. Ancient
      coalescence of extant haplotypes is further indicated by the paucity of fixed
      differences in haplotypes obtained from related species, a pattern expected under
      trans-specific evolution. Our data are consistent with models of frequency
      dependent selection on linked cytoplasmic male-sterility factors, the putative
      molecular basis of females in gynodioecious populations. However, associations
      between marker loci and the inferred male-sterility genes can be maintained only
      with very low rates of recombination. Heteroplasmy and recombination between
      divergent haplotypes imply unexplored consequences for the evolutionary dynamics
      of gynodioecy, a widespread plant breeding system.

PMID- 12192088
TI  - RNAi functions in cultured mammalian neurons.
AB  - In a wide range of organisms, double-stranded RNA triggers posttranscriptional
      gene silencing or RNA interference (RNAi). Small interfering RNAs, the 21-nt
      double-stranded RNA intermediates of this natural pathway, have became a powerful
      tool to knock down specific gene expression in mammalian cell lines and
      potentially will be useful for the analysis of loss-of-function phenotypes. In
      mammalian primary neuronal cultures, where genetic manipulations are especially
      difficult, RNAi might be developed into a highly efficacious tool to study the
      roles of specific genes in neuron development and functioning. Neurons, however,
      have been considered the most resistant to RNAi. We report here an application of
      RNAi to postmitotic primary neuronal cultures. Synthetic siRNA can be readily
      introduced into neurons and effectively inhibit the expression of endogenous and
      transfected genes.

PMID- 12192089
TI  - Crosslinked HIV-1 envelope-CD4 receptor complexes elicit broadly cross-reactive
      neutralizing antibodies in rhesus macaques.
AB  - The identification of HIV envelope structures that generate broadly cross
      reactive neutralizing antibodies is a major goal for HIV-vaccine development. In
      this study, we evaluated one such structure, expressed as either a gp120-CD4 or a
      gp140-CD4 complex, for its ability to elicit a neutralizing antibody response. In
      rhesus macaques, covalently crosslinked complexes of soluble human CD4 (shCD4)
      and HIV-1(IIIB) envelope glycoproteins (gp120 or gp140) generated antibodies that
      neutralized a wide range of primary HIV-1 isolates regardless of the coreceptor
      usage or genetic subtype. Ig with cross-reactive neutralizing activity was
      recovered by affinity chromatography with a chimeric single-chain polypeptide
      containing sequences for HIV(BaL) gp120 and a mimetic peptide that induces a CD4
      triggered envelope structure. These results suggest that covalently crosslinked
      complexes of the HIV-1 surface envelope glycoprotein and CD4 elicit broadly
      neutralizing humoral responses that, in part, may be directed against a novel
      epitope(s) found on the HIV-1 envelope.

PMID- 12192090
TI  - Novel adeno-associated viruses from rhesus monkeys as vectors for human gene
      therapy.
AB  - Tissues from rhesus monkeys were screened by PCR for the presence of sequences
      homologous to known adeno-associated virus (AAV) serotypes 1-6. DNA spanning
      entire rep-cap ORFs from two novel AAVs, called AAV7 and AAV8, were isolated.
      Sequence comparisons among these and previously described AAVs revealed the
      greatest divergence in capsid proteins. AAV7 and AAV8 were not neutralized by
      heterologous antisera raised to the other serotypes. Neutralizing antibodies to
      AAV7 and AAV8 were rare in human serum and, when present, were low in activity.
      Vectors formed with capsids from AAV7 and AAV8 were generated by using rep and
      inverted terminal repeats (ITRs) from AAV2 and were compared with similarly
      constructed vectors made from capsids of AAV1, AAV2, and AAV5. Murine models of
      skeletal muscle and liver-directed gene transfer were used to evaluate relative
      vector performance. AAV7 vectors demonstrated efficiencies of transgene
      expression in skeletal muscle equivalent to that observed with AAV1, the most
      efficient known serotype for this application. In liver, transgene expression was
      10- to 100-fold higher with AAV8 than observed with other serotypes. This
      improved efficiency correlated with increased persistence of vector DNA and
      higher number of transduced hepatocytes. The efficiency of AAV8 vector for liver
      directed gene transfer of factor IX was not impacted by preimmunization with the
      other AAV serotypes. Vectors based on these novel, nonhuman primate AAVs should
      be considered for human gene therapy because of low reactivity to antibodies
      directed to human AAVs and because gene transfer efficiency in muscle was similar
      to that obtained with the best known serotype, whereas, in liver, gene transfer
      was substantially higher than previously described.

PMID- 12192091
TI  - PDZ-domain interactions and apical expression of type IIa Na/P(i) cotransporters.
AB  - Type IIa Na/P(i) cotransporters are expressed in renal proximal brush border and
      are the major determinants of inorganic phosphate (P(i)) reabsorption. Their
      carboxyl-terminal tail contains information for apical expression, and interacts
      by means of its three terminal amino acids with several PSD95/DglA/ZO-1-like
      domain (PDZ)-containing proteins. Two of these proteins, NaPi-Cap1 and Na/H
      exchanger-regulatory factor 1 (NHERF1), colocalize with the cotransporter in the
      proximal brush border. We used opossum kidney cells to test the hypothesis of a
      potential role of PDZ-interactions on the apical expression of the cotransporter.
      We found that opossum kidney cells contain NaPi-Cap1 and NHERF1 mRNAs. For
      NHERF1, an apical location of the protein could be documented; this location
      probably reflects interaction with the cytoskeleton by means of the MERM-binding
      domain. Overexpression of PDZ domains involved in interaction with the
      cotransporter (PDZ-1/NHERF1 and PDZ-3/NaPi-Cap1) had a dominant-negative effect,
      disturbing the apical expression of the cotransporter without affecting the actin
      cytoskeleton or the basolateral expression of Na/K-ATPase. These data suggest an
      involvement of PDZ-interactions on the apical expression of type IIa
      cotransporters.

PMID- 12192092
TI  - In vivo modulation of nonphotochemical exciton quenching (NPQ) by regulation of
      the chloroplast ATP synthase.
AB  - Nonphotochemical quenching (NPQ) of excitation energy, which protects higher
      plant photosynthetic machinery from photodamage, is triggered by acidification of
      the thylakoid lumen as a result of light-induced proton pumping, which also
      drives the synthesis of ATP. It is clear that the sensitivity of NPQ is modulated
      in response to changing physiological conditions, but the mechanism for this
      modulation has remained unclear. Evidence is presented that, in intact tobacco or
      Arabidopsis leaves, NPQ modulation in response to changing CO(2) levels occurs
      predominantly by alterations in the conductivity of the CF(O)-CF(1) ATP synthase
      to protons (g(H)(+)). At a given proton flux, decreasing g(H)(+) will increase
      transthylakoid proton motive force (pmf), thus lowering lumen pH and contributing
      to the activation of NPQ. It was found that an approximately 5-fold decrease in
      g(H)(+) could account for the majority of NPQ modulation as atmospheric CO(2) was
      decreased from 2,000 ppm to 0 ppm. Data are presented that g(H)(+) is kinetically
      controlled, rather than imposed thermodynamically by buildup of DeltaG(ATP).
      Further results suggest that the redox state of the ATP synthase gamma-subunit
      thiols is not responsible for altering g(H)(+). A working model is proposed
      wherein g(H)(+) is modulated by stromal metabolite levels, possibly by inorganic
      phosphate.

PMID- 12192093
TI  - Functional plasticity of an antigen-specific memory CD4 T cell population.
AB  - The protective nature of memory immune responses is attributed largely to
      terminally differentiated memory T cells that retain memory of the antigen via
      the antigen receptor and memory of the effector functions that initially cleared
      the pathogen. It is not known whether a given population of antigen-specific
      memory T cells is endowed with functional flexibility to provide protective
      responses against antigens reencountered in different immunological contexts.
      Here, we examine functional properties of influenza hemagglutinin (HA)-specific
      memory CD4 T cells recovered from adoptive hosts that received in vitro-activated
      HA-specific T cell receptor-transgenic CD4 T cells 2 months to 1 year previously.
      We demonstrate that this HA-specific memory CD4 T cell population bearing a
      clonal T cell receptor can produce predominantly T helper 1 or T helper 2
      effector cytokines depending on the nature of the recall stimulus. Our findings
      reveal remarkable functional plasticity within an antigen-specific memory T cell
      population and have direct implications for modulating memory T cell function in
      vaccine design and treatments for autoimmune diseases.

PMID- 12192094
TI  - Host genetic variability and West Nile virus susceptibility.

PMID- 12192095
TI  - Comments to the editor concerning the paper entitled "Histidine suppresses food
      intake through its conversion into neuronal histamine" by Yoshimatsu et al.

PMID- 12192097
TI  - Cardiotonic steroids: potential endogenous sodium pump ligands with diverse
      function.
AB  - The highly conserved cardiotonic steroid (CS) binding site present on the
      ubiquitous membrane sodium pump, sodium, potassium-ATPase, appears to have been
      conserved by no force other than its capacity to bind CS: a family that includes
      plant-derived cardiac glycosides and putative endogenous vertebrate counterparts.
      Binding of ligand is inhibited by increased extracellular potassium. This implies
      functional coordination because inhibition of the sodium pump would be
      counterproductive when extracellular potassium is elevated. The interesting
      biology of the CS binding site continues to stimulate investigations into the
      identity of endogenous ligands, their role as pump regulators at the cellular
      level, and as mediators of body fluid balance and blood pressure regulation. In
      addition to inhibition of sodium and potassium transport, there is considerable
      recent evidence suggesting that the sodium pump may act as a cell signaling
      receptor activated by CS binding and responding by coordination of intracellular
      signaling pathways that can be dependent on and also independent of the reduction
      in transmembrane ion flux resulting directly from pump inhibition. This signaling
      may influence cell survival, growth, and differentiation. Recent insight into the
      biology of pump regulation by CS is reviewed.

PMID- 12192098
TI  - Anatomy of the spinal accessory nerve plexus: relevance to head and neck cancer
      and atherosclerosis.
AB  - The term spinal accessory nerve plexus may be defined as the spinal accessory
      nerve with all its intra- and extracranial connections to other nerves,
      principally cranial, cervical, and sympathetic. The term is not new. This review
      examines its applied anatomy in head and neck cancer and atherosclerosis. Over
      the centuries, general studies of neural and vascular anatomy and embryology
      formed a basis for the understanding upon which the plexus is described. During
      the past century, its anatomy and blood supply have come to be better understood.
      The importance of almost all of the plexus to head, neck, and upper extremity
      motor and sensory functions has come to be realized. Because of this
      understanding, surgical neck dissection has become progressively more
      conservative. This historical progression is traced. Even the most recent
      anatomic studies of the spinal accessory nerve plexus reveal configurations, new
      to many of us. They were probably known to classical anatomists, and not recorded
      in readily available literature, or not recorded at all. Human and comparative
      anatomic studies indicate that the composition of this plexus and its blood
      supply vary widely, even though within the same species their overall function is
      very nearly the same. Loss of any of these structures, then, may have very
      different consequences in different individuals. As a corollary to this
      statement, data are presented that the spinal accessory nerve itself need not be
      cut during surgical neck dissections for severe impairment to occur. In addition,
      data are presented supporting the theory that atherosclerosis by obstructing
      vessels to this plexus and its closely connected brachial plexus will very likely
      result in their ischemic dysfunction, often painful. Finally evidence, as well as
      theory, is stated concerning anatomic issues, methodology, outcome, and possible
      improvements in surgical procedures emphasizing conservatism.

PMID- 12192099
TI  - Mismatch repair genes and microsatellite instability as molecular markers for
      gynecological cancer detection.
AB  - Due to major developments in genetics over the past decade, molecular biology
      tests are serving promising tools in early diagnosis and follow-up of cancer
      patients. Recent epidemiological studies revealed that the risk for each
      individual to develop cancer is closely linked to his/her own genetic
      potentialities. Some populations that are defective in DNA repair processes, for
      example in Xeroderma pigmentosum or in the Lynch syndrome, are particularly prone
      to cancer due to the accumulation of mutations within the genome. Such
      populations would benefit from the development of tests aimed at identifying
      people who are particularly at risk. Here, we review some data suggesting that
      the inactivation of mismatch repair is often found in endometrial cancer and we
      discuss molecular-based strategies that would help to identify the affected
      individuals in families with cases of glandular malignancies.

PMID- 12192100
TI  - Determinants affecting physical activity levels in animal models.
AB  - Weight control is dependent on energy balance. Reduced energy expenditure (EE)
      associated with decreased physical activity is suggested to be a major underlying
      cause in the increasing prevalence of weight gain and obesity. Therefore, a
      better understanding of the biological determinants involved in the regulation of
      physical activity is essential. To facilitate interpretation in humans, it is
      helpful to consider the evidence from animal studies. This review focuses on
      animal studies examining the biological determinants influencing activity and
      potential implications to human. It appears that physical activity is influenced
      by a number of parameters. However, regardless of the parameter involved, body
      weight appears to play an underlying role in the regulation of activity.
      Furthermore, the regulation of activity associated with body weight appears to
      occur only after the animal achieves a critical weight. This suggests that
      activity levels are a consequence rather than a contributor to weight control.
      However, the existence of an inverse weight-activity relationship remains
      inconclusive. Confounding the results are the multifactorial nature of physical
      activity and the lack of appropriate measuring devices. Furthermore, many
      determinants of body weight are closely interlocked, making it difficult to
      determine whether a single, combination, or interaction of factors is important
      for the regulation of activity. For example, diet-induced obesity, aging, lesions
      to the ventral medial hypothalamus, and genetics all produce hypoactivity.
      Providing a better understanding of the biological determinants involved in the
      regulation of activity has important implications for the development of
      strategies for the prevention of weight gain leading to obesity and subsequent
      morbidity and mortality in the human population.

PMID- 12192101
TI  - The biochemistry and molecular biology of the glucose-6-phosphatase system.
AB  - Progress has continued to be made over the past 4 years in our understanding of
      the glucose-6-phosphatase (G6Pase) system. The gene for a second component of the
      system, the putative glucose-6-P transporter (G6PT), was cloned, and mutations in
      this gene were found in patients diagnosed with glycogen storage disease type 1b.
      The functional characterization of this putative G6PT has been initiated, and the
      relationship between substrate transport via the G6PT and catalysis by the
      system's catalytic subunit continues to be explored. A lively debate over the
      feasibility of various aspects of the two proposed models of the G6Pase system
      persists, and the functional/structural relationships of the individual
      components of the system remain a hot topic of interest in G6Pase research. New
      evidence supportive of physiologic roles for the biosynthetic functions of the
      G6Pase system in vivo also has emerged over the past 4 years.

PMID- 12192102
TI  - Antibodies to beta-amyloid decrease the blood-to-brain transfer of beta-amyloid
      peptide.
AB  - Amyloid-beta peptides (Abeta) play an important role in the pathophysiology of
      dementia of the Alzheimer's type and in amyloid angiopathy. Abeta outside the CNS
      could contribute to plaque formation in the brain where its entry would involve
      interactions with the blood-brain barrier (BBB). Effective antibodies to Abeta
      have been developed in an effort to vaccinate against Alzheimer's disease. These
      antibodies could interact with Abeta in the peripheral blood, block the passage
      of Abeta across the BBB, or prevent Abeta deposition within the CNS. To determine
      whether the blocking antibodies act at the BBB level, we examined the influx of
      radiolabeled Abeta (125I-Abeta(1-40)) into the brain after ex-vivo incubation
      with the antibodies. Antibody mAb3D6 (elan Company) reduced the blood-to-brain
      influx of Abeta after iv bolus injection. It also significantly decreased the
      accumulation of Abeta in brain parenchyma. To confirm the in-vivo study and
      examine the specificity of mAb3D6, in-situ brain perfusion in serum-free buffer
      was performed after incubation of 125I-Abeta(1-40) with another antibody mAbmc1
      (DAKO Company). The presence of mAbmc1 also caused significant reduction of the
      influx of Abeta into the brain after perfusion. Therefore, effective antibodies
      to Abeta can reduce the influx of Abeta(1-40) into the brain.

PMID- 12192103
TI  - Intracerebroventricular leptin administration reduces food intake in pregnant and
      lactating mice.
AB  - Leptin acts within the hypothalamus to diminish food intake. During pregnancy and
      lactation, both circulating leptin concentrations and food intake are elevated,
      suggesting an ineffectiveness of leptin to reduce food intake in these mice.
      Thus, this study tested the ability of intracerebroventricular (ICV) leptin
      administration to alter food intake during pregnancy and lactation. Mice during
      the first, second, and third trimesters of pregnancy, lactating mice on
      postpartum Day 7, and age-matched female mice were used. Plasma leptin
      concentrations averaged 2.9 +/- 0.3 ng/ml in control mice, increased steadily as
      pregnancy progressed (3.4 +/- 0.7, 29.8 +/- 4.5, and 40.5 +/- 0.7 ng/ml during
      the first, second, and third trimesters, respectively), and remained elevated on
      Day 7 postpartum (26.4 +/- 7.8 ng/ml). Mice were food deprived for 4 h, injected
      ICV with vehicle or leptin (1 micro g), and food intake was subsequently measured
      hourly for 3 hr, and after 24 hr. Vehicle-treated pregnant mice consumed
      marginally more food than cycling control mice, whereas nursing dams ate two to
      three times as much food as controls. As expected, ICV leptin administration
      reduced 24-hr food intake of control mice by 2 g, or approximately 50%. ICV
      administered leptin was as effective in reducing food intake of pregnant and
      lactating mice as observed in control mice. Thus, the elevated circulating leptin
      concentrations observed in pregnant and nursing mice did not alter the ability of
      ICV-administered leptin to diminish food intake. High plasma concentrations of
      leptin-binding proteins observed during pregnancy, and probably during lactation,
      may limit the amount of endogenous leptin reaching the hypothalamus, and may
      consequently enable increases in food intake concomitant with elevated plasma
      leptin during these nutritionally demanding periods.

PMID- 12192104
TI  - Effect of sildenafil on renin secretion in human subjects.
AB  - Sildenafil is a potent and selective inhibitor of the cyclic GMP-specific
      phosphodiesterase (PDE5) that is very effective in the treatment of male
      impotence. It inhibits breakdown of cyclic guanosine monophosphate (cGMP) formed
      in penile smooth muscle cells in response to stimulation by nitric oxide
      resulting in muscle relaxation. PDE5 is widely distributed in the body, being
      present in the vasculature, platelets, and kidneys. In the kidney, PDE5 is
      involved in the regulation of sodium excretion and renin secretion. The aim of
      the present investigation was to investigate the effect of sildenafil, in doses
      used clinically, on renin secretion in human subjects. The studies were performed
      in two groups of healthy normotensive subjects: one in which sodium intake was
      unrestricted, and one in which sodium intake was restricted to 600 mg/day. Blood
      pressure and heart rate were monitored throughout the study, and blood samples
      for the measurement of plasma cGMP and cAMP concentrations and plasma renin
      activity (PRA) were collected. After control measurements, the subjects ingested
      a capsule containing sildenafil or placebo. Cardiovascular measurements and blood
      sampling continued for the next 120 min. Sildenafil had only minor cardiovascular
      effects. Diastolic pressure tended to be lower and heart rate was generally
      higher after sildenafil than after placebo, but the differences were small.
      Sildenafil caused a prompt and sustained increase in plasma cGMP concentration
      and a more gradual increase in plasma cAMP concentration. After the subjects
      received placebo, there was a progressive decrease in PRA during the 2-hr
      observation period, presumably reflecting the circadian rhythm in renin
      secretion. In contrast, PRA failed to decrease after the subjects received
      sildenafil, thus indicating that sildenafil exerts a stimulatory action on renin
      secretion. This action on renin secretion may help explain why sildenafil only
      has minor effect on blood pressure despite the widespread distribution of PDE5 in
      vascular tissues.

PMID- 12192106
TI  - Genistein attenuates postischemic depressed myocardial function by increasing
      myofilament Ca2+ sensitivity in rat myocardium.
AB  - The present study investigated whether genistein, a broad-spectrum tyrosine
      kinase inhibitor, could increase the myofilament Ca(2+) sensitivity and partially
      reverse postischemic depressed myocardial function. Left ventricular papillary
      muscles were isolated from adult Wistar rats and loaded with the Ca2+ indicator,
      aequorin. The use of fluorocarbon immersion with hypoxia simulated a model of
      ischemia. Myofilament responsiveness to Ca2+ was evaluated from force-[Ca2+]i
      relationship recorded during tetani in papillary muscles. Protein levels of
      troponin I (TnI) were measured in postischemic papillary muscles with the Western
      blot technique. Isometric contraction was depressed during the period of ischemia
      and remained low after 60 min of reoxygenation without a corresponding
      significant change of peak [Ca2+]i in the control group (n = 7). In contrast, the
      depression of isometric contraction was ameliorated during ischemia in muscle
      preparations in the presence of genistein (2 micro M; n = 8), and postischemic
      depressed myocardial contractility partially recovered after a 60-min
      reperfusion. The myofilament Ca2+ responsiveness was significantly increased in
      papillary muscles in the presence of genistein. Protein levels of TnI were
      reduced in postischemic papillary muscles, whereas genistein partially restored
      decreased protein levels of TnI. Our results reveal that genistein produces an
      effective attenuation of postischemic depressed myocardial function and improves
      myofibrillar Ca2+ responsiveness in rat myocardium.

PMID- 12192105
TI  - Basolateral phosphate transport in renal proximal-tubule-like OK cells.
AB  - It is generally assumed that phosphate (Pi) effluxes from proximal tubule cells
      by passive diffusion across the basolateral (BL) membrane. We explored the
      mechanism of BL Pi efflux in proximal tubule-like OK cells grown on permeable
      filters and then loaded with 32P. BL efflux of 32P was significantly stimulated
      (P < 0.05) by exposing the BL side of the monolayer to 12.5 mM Pi, to 10 mM
      citrate, or by acid-loading the cells, and was inhibited by exposure to 0.05 mM
      Pi or 25 mM HCO3; by contrast, BL exposure to high (8.4) pH, 40 mM K+, 140 mM Na
      gluconate (replacing NaCl), 10 mM lactate, 10 mM succinate, or 10 mM glutamate
      did not affect BL 32P efflux. These data are consistent with BL Pi efflux from
      proximal tubule-like cells occurring, in part, via an electro-neutral sodium
      sensitive anion transporter capable of exchanging two moles of intracellular
      acidic H2PO4- for each mole of extracellular basic HPO4= or for citrate.

PMID- 12192107
TI  - Leptin predicts bone and fat mass after accounting for the effects of diet and
      glucocorticoid treatment in piglets.
AB  - The role of leptin in neonatal growth and bone metabolism has been investigated,
      but not simultaneously. The objectives of this study were to determine if leptin
      relates to bone mass during rapid growth; if consumption of maternal milk is
      related to elevated circulating concentrations of leptin resulting in higher fat
      mass; and if glucocorticoids result in higher fat mass and reduced bone mass due
      to elevated leptin. Thirty-two piglets were randomized to either a suckling or
      milk substitute plus either dexamethasone (DEX) or placebo injection for 15 days
      beginning at 5 days of age. Milk and blood samples were obtained at baseline, and
      after 15 days, blood was sampled again for measurement of leptin and bone
      biochemistry. Weight at baseline plus weight and length after 15 days were
      recorded, followed by measurement of whole body bone mineral content, bone area,
      and fat mass using dual energy x-ray absorptiometry. At baseline, plasma leptin
      was elevated in suckled piglets. Piglets that suckled had elevated fat mass as
      did those who received DEX. However, DEX resulted in suppressed weight and
      length, bone mass, and bone metabolism. Leptin was similar among groups after the
      15 days. After accounting for body size and treatment effects, piglet plasma
      leptin was predictive of bone and fat mass. Leptin circulating early postnatally
      is linked to body composition, specifically fat and bone mass. Elevations in fat
      mass and reductions in bone mass observed after 15 days of DEX treatment are not
      related to leptin metabolism. Both human and porcine neonates share similar
      characteristics with respect to relationships of leptin with fat and bone mass.

PMID- 12192108
TI  - Regulatory effects of eotaxin, eotaxin-2, and eotaxin-3 on eosinophil
      degranulation and superoxide anion generation.
AB  - Eosinophilic leukocytes have been implicated as primary effector cells in
      inflammatory and allergic diseases. When activated by cytokines, human
      eosinophils secrete and produce a variety of proinflammatory or tissue damaging
      substances. Although well known for their chemoattractant effects, little is
      known about the precise contribution of the eosinophil-selective chemokines,
      eotaxin, eotaxin-2, and eotaxin-3 to the effector functions of eosinophils. This
      forms the central focus of these investigations for which clone 15-HL-60 human
      eosinophilic cells were used as the in vitro model. Investigation results suggest
      that all three subtypes of eotaxin directly stimulate eosinophil superoxide anion
      generation that is inhibited by neutralizing eotaxin antibody or pretreatment of
      cells with the receptor antibody anti-CCR3. Pretreatment or co-treatment with
      each of the eotaxins augmented phorbol myristate-induced superoxide generation.
      Concentration-dependent degranulation of eosinophil peroxidase was noted for all
      three chemokines, and potentiation of calcium ionophore-induced degranulation was
      observed with eotaxin pretreatments. Results of interleukin-5 pretreatment
      studies suggest that the eotaxin chemokines may act cooperatively to enhance
      effector functions of eosinophils. Collectively, the present studies have
      advanced knowledge of the eotaxin family of chemokines to include eosinophil
      priming and modulation of eosinophil activation and secretion effector functions.

PMID- 12192109
TI  - Prior increase in metallothionein levels is required to prevent doxorubicin
      cardiotoxicity.
AB  - Many studies have shown that metallothionein (MT) can be increased significantly
      by different oxidative insults in multiple organ systems. However, the increase
      in MT production often fails to protect against oxidative tissue injury. On the
      other hand, recent studies using a cardiac-specific, MT-overexpressing,
      transgenic mouse model have shown that MT protects against oxidative heart
      injury. Thus, the present study was undertaken to test the hypothesis that prior
      increase in MT levels is required to prevent oxidative injury. Oxidative heart
      injury was induced by doxorubicin (DOX), an important anticancer drug that causes
      severe cardiotoxicity through oxidative stress. Cardiac-specific, MT
      overexpressing, transgenic mice and wild-type (WT) FVB mice were treated with DOX
      at 20 mg/kg. Four days after the treatment, MT concentrations were markedly
      elevated in the WT mouse heart. The elevated MT concentrations were comparable
      with those found in the transgenic mouse heart, which did not show further MT
      elevation in response to DOX challenge. Severe oxidative injury occurred in the
      heart of WT mice, including myocardial lipid peroxidation, morphological changes
      as examined by electron microscopy, high levels of serum creatine kinase
      activity, and decreased total glutathione concentrations in the heart. However,
      all of these pathological changes were significantly inhibited in the MT
      transgenic mice. Therefore, this study demonstrates that there is a correlation
      between MT induction and oxidative stress in the DOX-treated mouse heart.
      However, MT can protect the heart from oxidative injury only if it is present
      prior to induction of oxidative stress.

PMID- 12192110
TI  - Actions of immunosuppressor drugs on the development of an experimental ovarian
      tumor.
AB  - Immunosuppression has been related to the incidence of tumor apparition,
      including endocrine tumors. The intrasplenic ovarian tumor (luteoma) is a typical
      benign endocrine tumor that develops under high gonadotropin stimulation and,
      from the immunological perspective, is located in a critical organ involved in
      immune response. To establish if immunosuppression could alter the development of
      this experimental tumor, the effects of cyclosporin A (CsA) and dexamethasone
      (Dex) were evaluated. After surgery, tumor-bearing and sham animals were kept
      without treatment for 4 weeks; thereafter, they were distributed into CsA (25
      mg/kg), Dex (0.1 mg/kg), or vehicle (75:25 castor oil:ethanol) groups and were
      injected on alternate days for 50 days. Body weight was evaluated weekly. Animals
      were sacrificed after a jugular vein blood sample was obtained. Thymi were
      weighed. Tumors were measured and placed in formaline for histological studies.
      Serum luteinizing hormone (LH), follicle-stimulating hormone (FSH), prolactin
      (PRL), and estradiol were measured by radioimmunoassay. Hematological parameters
      were determined. CsA induced a significant decrease in survival rates both in
      tumor-bearing and sham animals (P < 0.01). Dex significantly impaired weight
      increase in both groups of animals. CsA induced a significant weight loss in sham
      animals, not observed in tumor-bearing animals. Dex induced thymus weight loss in
      both groups, whereas CsA induced thymus weight loss only in sham animals. Only
      Dex induced a decrease in lymphocyte number in both groups. CsA induced an
      increase in monocyte number only in sham animals. Treatments did not alter LH,
      FSH, or estradiol, whereas PRL was increased by CsA only in sham rats. Neither
      Dex nor CsA induced any significant variations in tumor volume, nor did they
      alter tumor histology. In addition, no visible metastases or alterations in other
      organs were observed. We conclude that, though immunological parameters were
      altered by the treatments, immunosuppressor drugs did not condition tumor
      development. In addition, tumors secrete one or more factor/s that counteract CsA
      effect.

PMID- 12192111
TI  - TNF-alpha sensitizes HT-29 colonic epithelial cells to intestinal lactobacilli.
AB  - The ability of the proinflammatory cytokine tumor necrosis factor-alpha (TNF
      alpha) to influence epithelial interleukin (IL)-8 responses to the intestinal
      bacterium Lactobacillus plantarum 299v was analyzed in the human HT-29 colonic
      epithelial cell line. In the absence of TNF-alpha, IL-8 mRNA expression was not
      detectable by Northern blot analysis in HT-29 cells alone or in HT-29 cells co
      cultured with L. plantarum 299v. However, TNF-alpha induced IL-8 mRNA expression,
      and co-culture of TNF-alpha-treated HT-29 cells with L. plantarum 299v
      significantly increased IL-8 mRNA expression above levels induced by TNF-alpha
      alone in an adhesion-dependent manner. The increase in IL-8 mRNA expression was
      not observed in TNF-alpha-treated HT-29/L. plantarum 299v co-cultures using heat
      killed lactobacilli or when L. plantarum adhesion was prevented using mannoside
      or a trans-well membrane. Paradoxically, IL-8 secretion was decreased in TNF
      alpha-treated HT-29 cells with L. plantarum 299v relative to cells treated with
      TNF-alpha alone. TNF-alpha-mediated responsiveness to L. plantarum 299v was
      further investigated by analyzing expression of a coreceptor for bacterial cell
      wall products CD14. HT-29 cells expressed CD14 mRNA and cell-surface CD14;
      however, TNF-alpha did not alter CD14 mRNA or cell-surface expression, and
      blockade of CD14 with monoclonal antibody MY4 did not alter the IL-8 response to
      L. plantarum 299v in TNF-alpha-treated HT-29 cells. These results indicate that
      although TNF-alpha sensitizes HT-29 epithelial cells to intestinal lactobacilli,
      the bacteria exert a protective effect by downregulating IL-8 secretion.

PMID- 12192112
TI  - Confined structures: basic crystallographic aspects.
AB  - The concept of a confined structure is introduced. The statistical properties of
      the structure factors for such structures are derived and the main features of
      the Patterson function are described. It is shown that the structure-factor
      distributions for the confined structures coincide with those derived for the
      rational index reflections of ordinary structures. Algorithms potentially useful
      for protein crystal structure solution are identified and checked via
      experimental applications.

PMID- 12192113
TI  - Least path criterion (LPC) for unique indexing in a two-dimensional decagonal
      quasilattice.
AB  - The least path criterion or least path length in the context of redundant basis
      vector systems is discussed and a mathematical proof is presented of the
      uniqueness of indices obtained by applying the least path criterion. Though the
      method has greater generality, this paper concentrates on the two-dimensional
      decagonal lattice. The order of redundancy is also discussed; this will help
      eventually to correlate with other redundant but desirable indexing sets.

PMID- 12192114
TI  - Crystallographic point groups of five-dimensional space. 1. Their elements and
      their subgroups.
AB  - The purpose of this work is to introduce a method with a view to obtaining the
      crystallographic point groups of five-dimensional space, i.e. the subgroups of
      the holohedries of these space crystal families. This paper is specifically
      devoted to numerical analysis, whereas the following ones deal with some
      applications to crystallography. These results have been obtained through a
      collaboration between two teams: H. Veysseyre (Institut Superieur des Materiaux)
      for the numerical analysis, R. Veysseyre, D. Weigel and Th. Phan (Ecole Centrale
      Paris) for the crystallographic part.

PMID- 12192115
TI  - Crystallographic point groups of five-dimensional space. 2. Their geometrical
      symbols.
AB  - Our previous paper emphasized a method for obtaining the crystallographic point
      groups of five-dimensional space, i.e. the subgroups of the crystal family
      holohedries. Moreover, it recalled the names of the crystal families and the
      symbols of their holohedries. These results being obtained, this paper gives a
      geometrical symbol to each of these point groups described as Weigel-Phan
      Veysseyre symbols (WPV symbols). In most cases, these symbols make it possible to
      reconstitute all the elements of the groups. The point symmetry operation
      symbols, which are the basis of the Hermann-Mauguin symbols (HM symbols) as well
      as of the WPV symbols, that have been defined from the cyclic groups generated by
      the five-dimensional point symmetry operations are recalled. The basic principles
      of the WPV system of crystallographic point-group symbols are explained and a
      list of 196 symbols of five-dimensional space out of 955 is given. All the
      information given by the WPV symbol of a point group is detailed and analysed
      through some examples and the study of the (hexagon oblique)-al crystal family.
      Finally, the polar point groups of five-dimensional space are specified.

PMID- 12192116
TI  - A hybrid Monte Carlo method for crystal structure determination from powder
      diffraction data.
AB  - A hybrid Monte Carlo algorithm for crystal structure determination from powder
      diffraction data is presented. The algorithm combines the key components of
      molecular dynamics and Monte Carlo simulations to achieve efficient sampling of
      phase space, allowing the crystal structure of capsaicin to be determined from
      powder diffraction data more effectively than by a simulated-annealing approach.
      The implementation of the algorithm, the choice of the simulation parameters and
      the performance of the algorithm are discussed.

PMID- 12192117
TI  - Reconsideration of the wavelength dependence of extinction: a gamma-ray case.
AB  - The wavelength dependence of extinction has been re-examined by means of new
      gamma-ray diffraction data collected from NiF(2) at 0.0205, 0.0265 and 0.0392 A.
      The standard model of extinction has been confirmed and substantiated by
      experimentally accessible parameters such as the intrinsic mosaic width. The
      predicted kinematic limit values are in accordance with the results from charge
      density analyses. The model proposed by Mathieson & Stevenson [Acta Cryst.
      (2002), A58, 185-189] leads to a purely phenomenological polynomial fit function.
      The extrapolated values are shown to be inconsistent with structure analyses
      based on extended gamma-ray data sets and cannot be recommended for use.

PMID- 12192118
TI  - Can a multipole analysis faithfully reproduce topological descriptors of a total
      charge density?
AB  - Total charge densities rho(r) of solid NH(3) have been derived using an ab initio
      crystalline molecular-orbital approach and also from multipole refinement of the
      structure factors obtained from the same charge density. Comparison of the
      topological features of these charge densities, as defined by the quantum theory
      of atoms in molecules, has been used to probe the ability of the multipole
      analysis to reproduce exactly known total charge-density distributions. For the
      most part, multipole refinement satisfactorily returns the features of the
      original density, although the fit to theoretical data is not as good as that to
      the experimental data. The one topological parameter that is poorly reproduced is
      the Laplacian nabla (2)rho(r(b)) at NH bond critical points.

PMID- 12192119
TI  - The best two-phase idealization of a sample in small-angle scattering.
AB  - The equations to be solved in order to determine the best discrete-valued
      approximation to a given electron or scattering-length density function are
      worked out. A simple illustration is reported.

PMID- 12192121
TI  - Concerning intensity profiles observed in the 'real experiment'.
AB  - The modifications of the kinematical and extinction-corrected intensity profiles
      caused by the divergence of the incident synchrotron-radiation beam and the
      diffraction by the monochromator system are considered. Expressions for the
      integral width as well as the full width at half-maximum are presented and
      discussed. The theoretical results are compared with observations.

PMID- 12192120
TI  - Aspherical-atom scattering factors from molecular wave functions. 1.
      Transferability and conformation dependence of atomic electron densities of
      peptides within the multipole formalism.
AB  - In this study, the feasibility of building a database of theoretical atomic
      deformation density parameters applicable to the construction of the densities of
      biomacromolecules and to the interpretation of their X-ray diffraction data is
      discussed. The procedure described involves generation of valence-only structure
      factors of tripeptides calculated from theoretical densities at the B3LYP level
      and the refinement of multipole parameters against these simulated data. Our
      results so far indicate that the backbone pseudoatoms extracted in such a way are
      highly transferable and fairly invariant with respect to rotations around single
      bonds in the peptide framework. The ultimate goal is to use the aspherical-atom
      database for improved macromolecular refinements that are based on high
      resolution data and for prediction of electrostatic properties of larger
      molecules.

PMID- 12192122
TI  - Rocking-curve width of sagittally bent Laue crystals.
AB  - The use of bent asymmetric Laue crystals to sagittally focus high-energy
      synchrotron X-rays calls for an understanding of the mechanisms affecting X-ray
      diffraction by such crystals. The rocking-curve width, a measurable quantity
      directly related to the distortion of the lattice planes, is the necessary first
      step towards such an understanding. A model is formulated for assessing the
      rocking-curve widths of sagittally bent Laue crystals, considering the elastic
      anisotropy. A method for depth-resolved measurement of the rocking curves was
      also developed to verify the model. The model successfully explains the wide
      range of rocking-curve widths of a large number of reflections from silicon
      crystals with two different orientations.

PMID- 12192123
TI  - A study on the position of boron atoms in (Y(0.6)Ca(0.4))(SrBa)(Cu(2.5)B(0.5))O(7
      delta).
AB  - The position of boron atoms in minute crystals of
      (Y(0.6)Ca(0.4))(SrBa)(Cu(2.5)B(0.5))O(7-delta) was studied by means of image
      processing based on the combination of high-resolution electron microscopy and
      electron diffraction. The structure image was obtained from a single image by
      image deconvolution based on the principle of maximum entropy. Its resolution is
      limited by that of the electron microscope. Then the image resolution was
      enhanced to about 1 A by direct-methods phase extension in combination with an
      empirical method of electron diffraction intensity correction. To study the
      substitution of boron atoms for copper, in the second cycle of diffraction
      intensity correction two different structure models were proposed. The one
      corresponding to a more reasonable atomic shape in the derived projected
      potential map (PPM) was accepted. In this model, the boron atoms are located at
      the 'chain' Cu sites.

PMID- 12192124
TI  - On the symmetry of simple 12- and 13-hedra.
AB  - The symmetry point groups for all combinatorially non-isomorphic simple 12- and
      13-hedra (7595 and 49566, respectively) are contributed in the paper for the
      first time. The most symmetrical polyhedra with automorphism group orders not
      less than 3 are drawn as Schlegel diagrams and characterized by the facet symbols
      and symmetry point groups.

PMID- 12192125
TI  - A revised proof of the metric properties of optimally superimposed vector sets.
AB  - A revised proof is given that the root-mean-square deviation between more than
      two vector sets after optimal superposition induces a metric. This corrects an
      error in a previous manuscript [Kaindl & Steipe (1997). Acta Cryst. A53, 809].

PMID- 12192128
TI  - New steroidal alkaloids from Fritillaria imperialis and their cholinesterase
      inhibiting activities.
AB  - Two new cevanine steroidal alkaloids, impericine (1) and forticine (2) along with
      known bases delavine (3), persicanidine A (4), and imperialine (5) were isolated
      from the bulbs of Fritillaria imperialis. The structures of impericine (1)
      [(20R,22S,25S)-5alpha-cevanin-23-ene-3beta,6beta,16beta-triol] and forticine (2)
      [(20S,22S,25S)-5alpha-cevanine-3beta,6beta-diol] were determined with the help of
      spectroscopic studies. These steroidal bases showed anti-acetylcholinesterase and
      anti-butyrylcholinesterase inhibitory activity.

PMID- 12192129
TI  - NMR study on the low-affinity interaction of human serum albumin with diclofenac
      sodium.
AB  - The low-affinity interaction between human serum albumin (HSA) and Diclofenac
      sodium (DCF) was studied using NMR techniques. Both 13C-NMR chemical shift and
      linewidth show that the dichlorophenyl ring in DCF molecule plays a primary role
      in its interaction with HSA. Langmuir adsorption isotherm was applied to evaluate
      the association constant K and the number of binding sites n of the drug/HSA
      complex through (1)H-NMR spin-lattice relaxation measurement. The results
      indicate that Langmuir isotherm can perfectly explain the capacity of low
      affinity binding of proteins for the ligands.

PMID- 12192130
TI  - Crystal structure of the alcoholates and the ansolvate of PNU-97018, an
      angiotensin II receptor antagonist.
AB  - The title compound, PNU-97018 [systemic name: 2-butyl-3,6,7,8,9,11-hexahydro-6,9
      dimethyl-3-([2'-(2H-tetrazol-5-yl)[1,1'-biphenyl]-4-yl]methyl)-6,9-ethano-4H
      imidazo[4,5-d]-pyridazino[1,2-a]pyridazin-4-one] is a newly developed angiotensin
      II receptor antagonist. The compound and its methanolate and ethanolate were
      characterized by X-ray crystallography and thermal analysis. The methanolate and
      ethanolate crystals have an almost identical molecular conformation and crystal
      packing. In both alcoholates, each alcohol molecule is fixed to the compound with
      a molar ratio of 1 : 1 by a hydrogen bond between the hydroxyl group of the
      alcohol molecule and the tetrazole group of the compound. The hydroxyl group of
      each alcohol molecule further links with the imidazole ring of the neighboring
      compound by hydrogen bond to form a hydrogen-bond network in both alcoholates. A
      tunnel-like structure that includes alcohol molecules is formed in each
      alcoholate. The ansolvate crystal showed completely different thermal and X-ray
      crystallographic characteristics from the alcoholates, where the compound
      molecules were directly linked by hydrogen bonds between the tetrazole group of a
      molecule and the imidazole ring of the neighboring molecule. The position of the
      hydrogen atom in the tetrazole ring was different between the ansolvate and
      alcoholates. Unlike alcoholates, a layer structure stacked on the b-c plane was
      observed in the ansolvate crystal. It was concluded that the molecular
      conformation and the arrangement of the compound molecules were largely different
      between ansolvate and alcoholate crystals.

PMID- 12192131
TI  - A new synthetic route towards the mono-O-protected anti-conformationally
      constrained pyrimidine acyclic nucleoside.
AB  - Novel synthetic approach to mono-O-protected anti-conformationally constrained
      pyrimidine acyclic nucleoside was attained from the coupling of lithiated 2,4
      dimethoxy-6-methylpyrimidine with 1-benzyloxy-3-(tert
      butyldiphenylsilyloxy)propan-2-one, followed by the sequential reactions of
      methylthiomethylation, cyclization, hydroxylation, and dealkylation.

PMID- 12192132
TI  - Pregnane and pregnane glycosides from the Malagasy plant, Cynanchum aphyllum.
AB  - A new 8,14-seco-pregnane type of steroid called cynaphyllogenin and its eight
      glycosides, cynaphyllosides A-H, were isolated from the aerial parts of Cynanchum
      aphyllum. The structures of these compounds were elucidated based on chemical and
      spectroscopic evidence.

PMID- 12192133
TI  - Iridoids and anthraquinones from the Malaysian medicinal plant, Saprosma
      scortechinii (Rubiaceae).
AB  - A further investigation of the leaves and stems of Saprosma scortechinii afforded
      13 compounds, of which 10 are new compounds. These were elucidated as the bis
      iridoid glucosides, saprosmosides G (1) and H (2), the iridoid glucoside, 6-O-epi
      acetylscandoside (3), and the anthraquinones, 1-methoxy-3-hydroxy-2-carbomethoxy
      9,10-anthraquinone (4), 1-methoxy-3-hydroxy-2-carbomethoxy-9,10-anthraquinone 3-O
      beta-primeveroside (5), 1,3-dihydroxy-2-carbomethoxy-9,10-anthraquinone 3-O-beta
      primeveroside (6), 1,3,6-trihydroxy-2-methoxymethyl-9,10-anthraquinone (7), 1
      methoxy-3,6-dihydroxy-2-hydroxymethyl-9,10-anthraquinone (8), 1,3,6-trihydroxy-2
      hydroxymethyl-9,10-anthraquinone 3-O-beta-primeveroside (9), and 3,6-dihydroxy-2
      hydroxymethyl-9,10-anthraquinone (10). Structure assignments for all compounds
      were established by means of mass and NMR spectroscopies, chemical methods, and
      comparison with published data. The new anthraquinones were derivatives of
      munjistin and lucidin.

PMID- 12192134
TI  - Studies on the constituents of Lonicera species. XVII. New iridoid glycosides of
      the stems and leaves of Lonicera japonica THUNB.
AB  - Four new iridoid glycosides, named L-phenylalaninosecologanin (1), 7-O-(4-beta-D
      glucopyranosyloxy-3-methoxybenzoyl)secologanolic acid (2), 6'-O-(7alpha
      hydroxyswerosyloxy)loganin (3) and (Z)-aldosecologanin (5), were isolated,
      together with a known one, newly named (E)-aldosecologanin (4), from the stems
      and leaves of Lonicera japonica. Their structures were established on the basis
      of chemical and spectral data.

PMID- 12192135
TI  - New farnesane-type sesquiterpenes, hedychiols A and B 8,9-diacetate, and
      inhibitors of degranulation in RBL-2H3 cells from the rhizome of Hedychium
      coronarium.
AB  - Two new farnesane-type sesquiterpenes, hedychiols A and B 8,9-diacetate, were
      isolated from the methanolic extract of the fresh rhizome of Hedychium coronarium
      KOEN. cultivated in Japan. Their stereostructures were elucidated on the basis of
      chemical and physicochemical evidence. The inhibitory effects of isolated
      constituents on the release of beta-hexosaminidase from RBL-2H3 cells were
      examined, and hedychilactone A and coronarin D were found to show the inhibitory
      activity.

PMID- 12192137
TI  - Scandium(III) trifluoromethanesulfonate catalyzed aromatic nitration with
      inorganic nitrates and acetic anhydride.
AB  - The rare earth metal(III) trifluoromethanesulfonate (rare earth metal(III)
      triflate, RE(OTf)3) was found to be an efficient catalyst for aromatic nitration
      with carboxylic anhydride-inorganic nitrate as the nitrating agent. In the
      presence of a catalytic amount of RE(OTf)3, the nitration of substituted benzenes
      proceeded to afford the corresponding nitrobenzenes. Especially, scandium(III)
      trifluoromethanesulfonate (scandium(III) triflate, Sc(OTf)3) is the most active
      catalyst among our tested Lewis acids. It was also found that acetic anhydride
      Al(NO3).9H2O is the most active nitrating agent in this system.

PMID- 12192136
TI  - Synthetic studies on selective type 4 phosphodiesterase (PDE 4) inhibitors. 1.
      Structure-activity relationships and pharmacological evaluation of 1,8
      naphthyridin-2(1H)-one derivatives.
AB  - In order to develop novel and orally active phosphodiesterase (PDE) 4 inhibitors,
      random screening was performed using our chemical library to find YM-10335
      possessing the 1,8-naphthyridin-2(1H)-one skeleton which is a completely
      different structure from rolipram. In this report, the syntheses and structure
      activity relationships of the YM-10335 derivatives were described. Some compounds
      showed selective inhibitory activities for PDE 4 derived from human peripheral
      blood cells and no effect on the other PDE types (1, 2, 3, 5). The inhibition of
      the tumor necrosis factor-alpha (TNF-alpha) release in vitro and the carrageenan
      induced pleurisy in rats were also described.

PMID- 12192138
TI  - Asymmetric synthesis of a selective endothelin A receptor antagonist.
AB  - An asymmetric synthesis of a selective endothelin A receptor antagonist 1b is
      described. Asymmetric conjugate addition of aryllithium derived from 18 to the
      chiral oxazoline 17 followed by hydrolysis afforded 15 in 96% ee via purification
      as (S)-(-)-1-phenylethylamine salt. Pd(OAc)(2)/dppf (1,1'
      bis(diphenylphosphino)ferrocene) catalyzed carbonylation followed by
      chemoselective addition of aryllithium derived from 23 which gave ketone 24.
      Diastereoselective reduction of the ketone with catecholborane followed by
      concomitant activation of the resulting alcohol and cyclization gave the late
      intermediate 26. Introduction of amino moiety on the pyridine ring by imidoyl
      rearrangement followed by deprotection and purification by crystallization
      furnished the enantiomerically pure target molecule 1b in 8% overall yield from
      16.

PMID- 12192139
TI  - Structure-activity relationships of 6-nitroquinazolines: dual-acting compounds
      with inhibitory activities toward both TNF-alpha production and T cell
      proliferation.
AB  - We synthesized various 6-nitroquinazolines by modifying the structure of compound
      1 and evaluated their inhibitory activities toward both TNF-alpha production and
      T cell proliferation responses. The presence of the unsubstituted piperazine ring
      at the C(7)-position was required for both inhibitory activities. In this series
      of compounds, 5d and 5f, containing the 4-fluorophenyl and 3,4-difluorophenyl
      moiety, respectively, at the C(4)-position, showed the suppressing effects toward
      both responses with low cell growth inhibition. Furthermore, the oral
      administration of these compounds mentioned above at doses of 30 and 100 mg/kg
      also resulted in significant inhibition of TNF-alpha production induced by LPS in
      vivo.

PMID- 12192140
TI  - Synthesis of optically active homocysteine from methionine and its use in
      preparing four stereoisomers of cystathionine.
AB  - In order to synthesize four stereoisomers of cystathionine (CYT), D- and L
      homocysteines (D- and L-Hcy) were synthesized from methionine (Met) by a facile
      procedure. L-Met was reacted with dichloroacetic acid in concentrated
      hydrochloric acid under reflux to give (4S)-1,3-thiazane-2,4-dicarboxylic acid
      hydrochloride [(4S)-TDC.HCl]. L-Hcy was obtained by treatment of (4S)-TDC.HCl
      with hydroxylamine. D-Hcy was also synthesized from D-Met via (4R)-TDC.HCl
      intermediate. The obtained D- and L-Hcy were condensed with (R)- and (S)-2-amino
      3-chloropropanoic acid hydrochlorides under alkaline conditions to give four
      stereoisomers of CYT.

PMID- 12192141
TI  - Regulation of lithospermic acid B and shikonin production in Lithospermum
      erythrorhizon cell suspension cultures.
AB  - Cell suspension cultures of Lithospermum erythrorhizon produced a large amount of
      lithospermic acid B, a caffeic acid tetramer, as well as shikonin derivatives
      (each ca. 10% of dry wt.) when cultured in shikonin production medium M-9.
      Various culture factors for increasing the production of lithospermic acid B were
      investigated. Lithospermic acid B production was inhibited by 2, 4-D or NH4+,
      whereas it was stimulated by Cu2+. These regulatory patterns were similar to
      those for the production of shikonin derivatives in these cell cultures,
      suggestive of close relations and similar metabolic regulation between the
      production of these compounds. Cultivation under light illumination, however,
      showed that these metabolisms were independently regulated. In particular, blue
      light showed a stimulatory effect on lithospermic acid B production, while
      shikonin production was strongly inhibited, indicative of an effective condition
      for lithospermic acid B production.

PMID- 12192142
TI  - Isolation and structure determination of six glucocerebrosides from the starfish
      Luidia maculata.
AB  - Two new glucocerebrosides, luidiacerebroside A (2) and B (6), were isolated from
      the cerebroside molecular species obtained from the less polar fraction of the
      CHCl3/MeOH extract of the starfish Luidia maculata using HPLC. Four known
      cerebrosides, CE-2b (1), astrocerebroside B (3), acanthacerebroside B (4), and CE
      3-2 (5) have also been isolated and characterized. The structures of these
      cerebrosides were determined on the basis of chemical and spectroscopic evidence.
      Mass spectrometry of dimethyl disulfide derivatives was useful for the
      determination of the double-bond position in the long-chain base.

PMID- 12192143
TI  - Five triterpene glycosides from Oxytropis myriophylla.
AB  - Four new triterpene glycosides: one cycloartane-type glycoside and three
      azukisapogenol glycosides were isolated together with one known oleanene
      bisdesmoside from the Mongolian natural medicine, Oxytropis myriophylla.

PMID- 12192144
TI  - Isoflavonoid glycosides from the rhizomes of Iris germanica.
AB  - Four isoflavone glycosides were isolated from the rhizomes of Iris germanica.
      Compounds 1 and 2 are new, while compounds 3 and 4 are known isoflavone
      glycosides. These compounds were identified as iriskashmirianin 4'-O-beta-D
      glucoside (1), nigricin 4'-O-beta-D-glucoside (2), irilone 4'-O-beta-D-glucoside
      (3) and iridin (4). Their structures were determined with the help of
      spectroscopic methods.

PMID- 12192145
TI  - Capillary electrophoresis of anthraquinones from Cassia siamea.
AB  - The separation and determination of two anthraquinones, emodin and chrysophanol,
      and two bianthraquinones, cassiamin A and cassiamin B, were achieved by capillary
      electrophoresis (CE). The running electrolyte used in this method was 0.05 M
      hydroxypropyl-gamma-cyclodextrin in 0.1 M borate buffer (pH 9) containing 10%
      acetonitrile, with an applied voltage of 20 kV. Application of this technique in
      the determination of the main bianthraquinones, cassiamin A and cassiamin B, of
      Cassia siamea is demonstrated in this paper.

PMID- 12192146
TI  - Iridoid glucosides from Veronica hederifolia.
AB  - A new iridoid glucoside, urphoside A, and six known iridoid glucosides,
      pikuroside, aucubin, veronicoside, catalposide, amphicoside, and verminoside,
      were isolated from Veronica hederifolia together with a known megastigmane
      glucoside, 3-hydroxy-5,6-epoxy-beta-ionol-9-O-beta-D-glucopyranoside, and a
      hexitol, dulcitol. The structures of the isolated compounds were established by
      the extensive 1D- and 2D-NMR spectroscopy.

PMID- 12192147
TI  - Design, synthesis and biological activity of rigid cannabinoid CB1 receptor
      antagonists.
AB  - The design, synthesis and biological activities of potent pyrazole-based
      tricyclic CB1 receptor antagonists (2) are described. The key synthetic step
      involves the ring closure of the lithiated alpha, gamma-keto ester adduct (4).
      The optimal nitroderivative (28) in this series exhibits a high CB1 receptor
      affinity (pKi=7.2) as well as very potent antagonistic activity (pA2=8.8) in
      vitro. The regioselectivity of the pyrazole ring closure is shown to depend
      strongly on the aromatic substitution pattern of the applied arylhydrazine.

PMID- 12192148
TI  - Structural analysis of partially acetylated glycosides by refocused-decoupled
      insensitive nuclei enhanced by polarization transfer (INEPT) experiments: a
      qualitative and quantitative method.
AB  - The application of the refocused-decoupled INEPT pulse sequence in 13C-NMR
      spectroscopy allows, in conjonction with computer simulations, a straightforward
      editing of the spectra of a raw mixture of glycosidic compounds.

PMID- 12192149
TI  - Efficient synthesis of antihyperglycemic (S)-alpha-aryloxy-beta-phenylpropionic
      acid using a bifunctional asymmetric catalyst.
AB  - Antihyperglycemic (S)-alpha-aryloxy-beta-phenylpropionic acid was prepared using
      catalytic asymmetric cyanosilylation as a key reaction to construct alpha
      oxycarboxylic acid moiety.

PMID- 12192150
TI  - A new ent-kaurane diterpenoid glycoside from the leaves of Cussonia bojeri, a
      Malagasy endemic plant.
AB  - A new ent-kaurane diterpene glycoside, beta-D-glucopyranosyl 17-hydroxy-ent
      kauran-19-oate-16-O-beta-D-glucopyranoside (4) was isolated from the dried leaves
      of Cussonia bojeri SEEM., together with four known compounds identified as
      16beta,17-dihydroxy-kauran-19-oic acid (1), beta-D-glucopyranosyl 16beta,17
      dihydroxy-(-)-kauran-19-oate (2), paniculoside IV (3), and rutin (5). The
      structure of 4 was deduced on the basis of chemical and spectroscopic evidence.

PMID- 12192152
TI  - Lindbladione and related naphthoquinone pigments from a myxomycete Lindbladia
      tubulina.
AB  - Lindbladione (1), 7-methoxylindbladione (2), and 6, 7-dimethoxylindbladione (3)
      have been isolated from a myxomycete Lindbladia tubulina and their structures
      were elucidated by spectral data.

PMID- 12192151
TI  - A new acylated triterpene from the roots of Chaenomeles japonica.
AB  - A new acylated triterpene together with prunasin, (-)-epicatechin, daucosterol,
      and three triterpenes, ursolic, oleanolic, and pomolic acids was isolated from
      the root of Chaenomeles japonica (THUNB.) LINDL. (Rosaceae) and determined to be
      3-O-(E)-3, 5-dihydroxycinnamoylursolic acid on the basis of NMR and FAB-MS
      experiments.

PMID- 12192153
TI  - Characterization and quantitation of clarithromycin polymorphs by powder X-ray
      diffractometry and solid-state NMR spectroscopy.
AB  - Characterization of clarithromycin polymorph was performed by solid-state cross
      polarization and magic angle spinning (CP/MAS) 13C-NMR spectroscopy. Two
      polymorphs, form II and form I, of clarithromycins indicated characteristic
      resonances of C1 carbonyl carbon at 176.2 and 175.2 ppm, respectively. Since each
      peak of C1 carbon was well separated in the spectrum of the two polymorphs, we
      performed quantitative analysis of the polymorphic fraction from the peak area of
      these peaks. The peak area of form I was found to linearly increase with an
      increase of its content, with a correlation coefficient of above 0.99. Solid
      state NMR was found to be a useful technique to determine the characteristics of
      the polymorphic forms.

PMID- 12192154
TI  - A chiral ligand-mediated asymmetric addition of a lithium BHA ester enolate to an
      aldehyde.
AB  - The asymmetric reaction of a lithium enolate generated from a BHA (2, 6-di-tert
      buty-4-methoxyphenyl) propanoate was allowed to react with benzaldehyde in the
      presence of a diether-type chiral ligand affording the corresponding anti-aldol
      product in a moderate enantioselectivity. A tetradentate ligand induced better
      enantioselectivity albeit relative loss of anti-selectivity. A variation of
      lithiating amide agent affected the selectivity, indicating involvement of an
      amine as a component of the mixed aggregate. Absolute configuration of some of
      the aldol products was determined by standard transformations.

PMID- 12192155
TI  - Effective isolation of magnesium lithospermate B and its inhibition of aldose
      reductase and fibronectin on mesangial cell line.
AB  - We developed an effective isolation method of magnesium lithospermate B from
      Salviae miltiorrhizae Radix and found for the first time that magnesium
      lithospermate B shows strong in vitro inhibition (IC50=0.04 microM) of aldose
      reductase (AR), 2.5 times than that of clinically used epalrestat (IC50=0.1
      microM) and accumulation of fibronectin dose dependently.

PMID- 12192156
TI  - Biomimetic oxidation of 2-methylimidazole derivative with a chemical model system
      for cytochrome P-450.
AB  - A chemical model system for cytochrome P-450, consisting of tetraphenylporphyrin
      manganese chloride (TPPMnCl) and iodosylbenzene, efficiently oxidized 2
      methylimidazole to 2-methylimidazolone. This system was next applied to 4-(2
      methyl-1-imidazolyl)-2,2-diphenylbutyramide, a muscarinic acetylcholine receptor
      antagonist under clinical trial, affording the previously unisolated imidazole
      ring 5-mono-oxidized derivative that is considered to be the precursor of the
      main metabolites. This system, which is superior to the copper-ascorbate system,
      should be applicable to in vitro studies of various drugs containing the 2
      methylimidazole moiety.

PMID- 12192157
TI  - First total synthesis of a novel monoterpenoid isoquinoline alkaloid, (+/-)
      alangine.
AB  - The structure including the stereochemistry of a novel monoterpenoid isoquinoline
      alkaloid, alangine, was confirmed by total synthesis via N-acyliminium
      cyclization to construct the isoquinoline skeleton and reductive cleavage of
      vinyl epoxide with Pd(0) catalyst.

PMID- 12192159
TI  - Hepatitis A booster vaccine in children after infant immunization.
AB  - BACKGROUND: Hepatitis A vaccine provides long term protection against hepatitis A
      infection in adults and children older than 2 years of age. Few data are
      available regarding children younger than 2 years of age. METHODS: Children who
      were vaccinated in infancy with hepatitis A vaccine were revaccinated at 4 years
      of age, and antibody titers were followed. Forty-four subjects who had been
      vaccinated with hepatitis A vaccine [Havrix, 360 enzyme-linked immunosorbent
      assay units (EU)] at the age of 2, 4 and 6 months were revaccinated with 720 EU
      of inactivated hepatitis A vaccine (Havrix) at 4 years of age. RESULTS: Geometric
      mean titer (GMT) of 44 evaluable cases was 41 mIU/ml and 34 children (77.3%) were
      seropositive before the booster dose. Postvaccination blood samples were obtained
      from 37 cases. One month after booster dose GMT increased to 2884 mIU/ml, and all
      subjects were seropositive. Ten seronegative cases also seroconverted. The GMT of
      the seropositive cases showed anamnestic response after the booster dose (57
      mIU/ml before booster dose, 5623 mIU/ml after the booster). No serious adverse
      event was seen after the booster dose. CONCLUSION: We conclude that childhood
      hepatitis A virus revaccination after infant immunization is highly immunogenic
      and safe.

PMID- 12192158
TI  - Clinically significant infections with organisms of the Streptococcus milleri
      group.

PMID- 12192160
TI  - Enteric pathogens, intestinal permeability and nitric oxide production in acute
      gastroenteritis.
AB  - BACKGROUND: Aboriginal children hospitalized with diarrheal disease in northern
      Australia have high rates of acidosis, hypokalemia and osmotic diarrhea, as well
      as abnormal small bowel permeability and elevated nitric oxide (NO) production.
      METHODS: In a study of 291 diarrheal admissions and 84 controls, we examined the
      relationship of diarrheal severity outcomes with specific enteric pathogens. NO
      production was measured by urine nitrate plus nitrite excretion on a low nitrate
      diet, small bowel permeability by the lactulose:rhamnose ratio on a timed blood
      specimen and stool pathogens by standard microbiologic investigations and PCR.
      RESULTS: The addition of diagnostic tests for diarrheagenic Escherichia coli to
      standard stool microbiologic testing increased the rate of specific diagnoses
      from 53% to 75%, but with multiple pathogens isolated from 34%. The most
      frequently isolated pathogens from diarrheal patients were enteroaggregative E.
      coli (28.9%), rotavirus (26.5%), enteropathogenic E. coli (17.2%), Salmonella
      spp. (10.7%), Cryptosporidium parvum (7.2%) and Strongyloides stercoralis (7.2%).
      High geometric mean permeability ratios (95% confidence intervals) occurred with
      rotavirus (19.6; 15.3 to 25.1), enteroaggregative E. coli (21.2; 15.3 to 29.3)
      and Cryptosporidium (23.0; 15.1 to 35.1) compared with 9.4 (6.8 to 13.1) for no
      pathogens. NO production was highest for Cryptosporidium (3.7; 2.3 to 6.1)
      compared with 0.6 (0.4 to 1.1) for no pathogens. Multiple regression analysis
      revealed significant associations (P < 0.001) for rotavirus with acidosis and
      osmotic diarrhea, for Strongyloides with wasting and hypokalemia and for
      Cryptospoidium with severe and prolonged diarrhea. CONCLUSIONS: Cryptosporidium,
      Strongyloides, rotavirus and enteroaggregative E. coli are important contributors
      to the severe manifestations of acute gastroenteritis in Australian Aboriginal
      children.

PMID- 12192161
TI  - Antiviral treatment of varicella in pediatric practice in the Latium region of
      Italy: results of an observational study.
AB  - BACKGROUND: The optimal management of chickenpox in children is a controversial
      issue, at least in Europe. This study was designed to describe chickenpox in
      children and its reported management by pediatricians working for the National
      Health Service in the Latium region of Italy. METHODS: A questionnaire collected
      information on the duration, complications and treatment of the disease between
      September, 1998, and May, 1999, by participant pediatricians who enrolled 1094
      patients in community pediatric practice. RESULTS: Secondary and tertiary cases
      of the disease in the same household were more severe than the primary cases.
      Acyclovir was given to 50% of the children, with a tendency to treat more
      severely ill children. The duration of the disease was significantly less in
      children receiving acyclovir within the first 24 h of rash (7.6 days 9.0). No
      complications requiring hospitalization were reported. CONCLUSIONS: The use of
      antiviral drugs is not consistent among pediatricians. Clear guidelines are
      needed to minimize the use of drugs and to identify children who are likely to
      benefit most from antiviral therapy.

PMID- 12192162
TI  - Therapeutic drug monitoring of indinavir and nelfinavir to assess adherence to
      therapy in human immunodeficiency virus-infected children.
AB  - INTRODUCTION: Adherence to highly active antiretroviral therapy is required to
      obtain an optimal long term virologic response rate of HIV-1-infected children.
      Plasma concentrations of protease inhibitors (PIs) outside the limits of the
      reference values indicate nonadherence to antiretroviral therapy in adults. We
      studied during a 2-year follow-up period routinely taken plasma protease
      inhibitor concentrations to assess adherence to antiretroviral therapy in HIV-1
      infected children. METHODS: In 40 children (ages 3 months to 18 years) blood
      samples were taken at regular outpatient visits every 12 weeks after the start of
      highly active antiretroviral therapy and analyzed for plasma concentrations of
      indinavir or nelfinavir by high performance liquid chromatography and for plasma
      HIV-1 RNA load. The percentage of samples fulfilling the criteria for adherence
      was assessed for each child by three methods. For each sample a concentration
      ratio was calculated by dividing the concentration in that sample by the time
      adjusted population value. According to Method 1 concentration ratios below or
      above concentration ratio limits (CORALs) of population data obtained in adults
      were highly indicative of nonadherence. Because many children have high PI
      levels, Method 2 evaluated plasma samples of PIs with only the lower CORAL.
      According to Method 3 only children with plasma samples below the limit of
      quantification (0.04 mg/l) were considered noncompliant. Differences in adherence
      rate between virologic responders and virologic nonresponders and between
      adherence rates and the two protease inhibitors were analyzed. The cumulative
      incidence of HIV-1 RNA levels >500 copies/ml in children was calculated. RESULTS:
      Thirty-one children started treatment with indinavir, and nine children started
      treatment with nelfinavir. The median adherence rates for indinavir as determined
      by methods 1, 2 and 3 were 54% [interquartile range (IQR), 25 to 69%], 67% (IQR
      50 to 92%) and 80% (IQR 63 to 100%), respectively. For nelfinavir median
      adherence rates of 60% (IQR 39 to 75%), 100% (IQR 67 to 100%) and 100% (IQR 100
      to 100%) were observed. Adherence rates calculated with Method 2 were
      significantly higher in virologic responders ( = 0.04). Adherence rates
      calculated with Methods 2 and 3 were significantly lower in children using
      indinavir compared with those using nelfinavir ( = 0.02 and = 0.02,
      respectively). CONCLUSION: Calculation of adherence rates using the lower limit
      of CORALs of indinavir or nelfinavir in children may be a useful measurement for
      the assessment of nonadherence to antiretroviral therapy in children.

PMID- 12192164
TI  - Claims of equivalence in randomized controlled trials of the treatment of
      bacterial meningitis in children.
AB  - OBJECTIVE: To evaluate claims of therapeutic equivalence in studies of the
      treatment of bacterial meningitis in children. METHODS: We performed a systematic
      review of randomized controlled trials of antimicrobial therapy for bacterial
      meningitis in children indexed in MEDLINE and published after 1980 and that
      claimed equivalency. The sample size of each trial was compared with the minimum
      sample size needed to rigorously claim equivalence. The primary endpoint was case
      fatality. RESULTS: Twenty-five studies were identified that met the inclusion
      criteria. Two of these were specifically designed to test equivalence, and the
      remaining based claims of equivalence on failed tests of superiority. The
      majority of these trials (24 of 25) that claimed equivalence had sufficient
      sample size to exclude a 20% difference in mortality between the tested
      therapies. Only 3 of the 25 trials could exclude a 10% difference in mortality.
      CONCLUSION: Few of the trials in this study had sufficient sample size to claim
      equivalence within 10% of the expected mortality. Proving equivalency is
      challenging because large sample sizes are often needed to ensure adequate
      statistical power to rule out clinically important differences between the
      standard of care and new therapies.

PMID- 12192163
TI  - Safety and immunogenicity of meningococcus serogroup C conjugate vaccine
      administered as a primary or booster vaccination to healthy four-year-old
      children.
AB  - BACKGROUND: Meningococcal C conjugate (Men C) vaccines have been routinely used
      in the UK since November, 1999. Little information exists regarding antibody
      persistence or immunologic memory after infant vaccination or response to a first
      dose at 4 years. METHODS: Ninety-five children immunized at 2, 3 and 4 months of
      age with 0 or 3 doses of Men C vaccine, boosted with Men C or meningococcal A/C
      polysaccharide vaccine at 12 months, received a single dose of Men C vaccine at 4
      years; 103 age-matched controls were recruited. Pre- and postvaccination Men C
      IgG (enzyme-linked immunosorbent assay) antibody titers and serum bactericidal
      activity (SBA) were measured. Safety data were also collected. RESULTS: Baseline
      SBA titers of > or =1/4 were observed in 87% of children after at least 3 doses
      of Men C vaccine in infancy compared with 21% of controls. Reciprocals of
      postvaccination SBA geometric mean titers in those with four prior doses [3803
      (95% confidence interval 3489, 4146)] were significantly higher than controls [33
      (95% confidence interval 20, 55)] ( < 0.001). Memory was attenuated by the 12
      month meningococcal A/C polysaccharide booster [734 (95% confidence interval 484,
      1115)] ( < 0.001). All children had IgG responses to a first dose of Men C
      vaccine, 80% achieving SBA titers of > or =1/4 (77% > or =1/8). The vaccine was
      safe and well-tolerated. CONCLUSION: Infant immunization with Men C produced
      persistent antibody and immunologic memory at 4 years. All children made IgG
      antibodies after a first dose at this age, with 80% showing bactericidal
      activity. Clarification of the best measures of Men C vaccine-induced protection
      is needed, through correlation of immunogenicity data such as this with UK
      vaccine efficacy estimates.

PMID- 12192165
TI  - Prevalence, rate of persistence and respiratory tract symptoms of Chlamydia
      pneumoniae infection in 1211 kindergarten and school age children.
AB  - BACKGROUND: is a common cause of respiratory disease, but little is known about
      asymptomatic infection, duration of persistent respiratory tract infection and
      seasonal changes of prevalence in a normal large sample size pediatric
      population. METHODS: We studied the prevalence of infection in 1211 children of 3
      age groups: 3- to 4-year-old kindergarten children ( = 184) and schoolchildren
      attending first and second ( = 353) or seventh and eighth grade classes ( = 674).
      Polymerase chain reaction and enzyme immunoassay detection (PCR-EIA) of throat
      swabs were used. Respiratory tract symptoms (cough, rhinitis, earache or sore
      throat) were recorded in 1028 schoolchildren. Follow-up examinations in PCR
      positive patients were performed until negative. RESULTS: PCR was positive in 68
      children (5.6%) without significant age and gender related differences in
      prevalence. Epidemics were confirmed with a prevalence up to 24% in a primary
      school in December and April. In schoolchildren, asymptomatic infection was a
      common feature, reaching 54% (32 of 59) of PCR-EIA positives. The rate of
      asymptomatic infection was 6% (32 of 531 schoolchildren without symptoms). Of the
      32 asymptomatic PCR-EIA positives, 26 (81%) were children attending seventh and
      eighth grade classes. In 3 children PCR-EIA remained positive at 3 to 5 weeks and
      became negative during the next 7 to 9 weeks. One of 2 schoolchildren with
      persistent infection was asymptomatic. CONCLUSIONS: We conclude that infection is
      common in the childhood population studied with seasonal variations in prevalence
      and epidemic-like occurrence. Asymptomatic infection occurs, especially in
      teenagers, but persistent infection is rare.

PMID- 12192166
TI  - Pediatric sentinel surveillance of vaccine-preventable diseases in Italy.
AB  - BACKGROUND: Planning and evaluating vaccination programs depend on reliable
      systems of monitoring disease incidence in the community. In Italy vaccine
      preventable diseases are subject to statutory notification, but they are often
      unreported. In January, 2000, a pediatric sentinel network was launched, with the
      aim of monitoring in a timely and accurate way the geographic and temporal trends
      of vaccine-preventable diseases. METHODS: The network consists of National Health
      System primary care pediatricians; participation is voluntary. The diseases under
      surveillance include measles, mumps, rubella, pertussis and varicella. Case
      definitions are based on specific clinical criteria, and pediatricians report
      cases on a monthly basis. Incidence rates are estimated and compared with those
      obtained by statutory notifications. The proportion of vaccinated cases is also
      computed. RESULTS: In 2000 an average of 468 pediatricians participated each
      month of a total of 7276 pediatricians under contract for primary care by the
      National Health System. The population under surveillance consisted of 371 670
      children younger than 15 years (of a national total of 8.347.804 children of the
      same age). The annual national incidence per 100.000 children was estimated at
      5345 for varicella, 1972 for mumps, 279 for pertussis, 108 for rubella and 62 for
      measles, although wide variations were observed among geographic areas. The
      national estimates are 3 to 7 times higher than those obtained through statutory
      notifications. For all of the diseases the ratio between the two sources of data
      was significantly higher in southern Italy, compared with the rest of the
      country. The proportion of vaccinated cases was similar for measles and rubella
      (21 and 17%) but was approximately 3 times higher for mumps (59%). Most (74%) of
      the vaccinated mumps cases had received the Rubini vaccine strain. CONCLUSIONS:
      The sentinel surveillance system is considerably more sensitive than statutory
      notifications, particularly in southern Italy. The high percentage of mumps cases
      vaccinated with the Rubini strain indicates a reduced effectiveness of this
      vaccine. Although further improvements are needed, pediatrician-based sentinel
      surveillance is a useful tool for evaluating vaccine-preventable disease trends.

PMID- 12192167
TI  - Safety and immunogenicity of a combination diphtheria-tetanus toxoids-acellular
      pertussis-hepatitis B vaccine administered at two, four and six months of age
      compared with monovalent hepatitis B vaccine administered at birth, one month and
      six months of age.
AB  - OBJECTIVE: To evaluate the safety and immunogenicity of diphtheria-tetanus
      toxoids-acellular pertussis (DTPa)-hepatitis B (HepB) combination vaccine given
      at 2, 4 and 6 months of age compared with monovalent HepB vaccine given at birth,
      1 month and 6 months of age and DTPa vaccine given at 2, 4 and 6 months of age.
      METHODS: Healthy infants were randomized to receive a combination DTPa-HepB
      vaccine (diphtheria and tetanus toxoids, acellular pertussis antigens and
      hepatitis B surface antigen), concomitantly with type b and oral poliovirus
      vaccines at 2, 4 and 6 months of age (Group 1) or HepB vaccine given at birth, 1
      month and 6 months of age and DTPa, type b and oral poliovirus vaccines given at
      2, 4 and 6 months of age (Group 2). Antibody responses were evaluated at birth, 2
      months and 7 months of age. Safety was evaluated after each immunization using
      diary cards and parental interviews. RESULTS: One month after the third dose (7
      months of age), the geometric mean concentration of antibody to hepatitis B
      surface antigen was approximately 3.5-fold higher in Group 2 than in Group 1
      infants (3643 and 1052 mIU/ml, respectively; < 0.001). Nevertheless the rates of
      seroprotection to HepB (antibody to hepatitis B surface antigen > or =10 mIU/ml)
      in Groups 1 and 2 were similar, 99 and 100%, respectively. Also the
      postvaccination geometric mean concentrations and rates of seroprotection or
      vaccine response to all of the other vaccine antigens evaluated were similar or
      greater in Group 1 than in Group 2. The rates of adverse events were similar
      between the two groups, with fussiness and soreness at any injection site
      reported most frequently. CONCLUSIONS: The DTPa-HepB combination vaccine was safe
      and immunogenic when given to infants at 2, 4 and 6 months of age. Equivalent
      rates of seroprotection to hepatitis B were achieved despite a reduction of the
      interval between the second and third doses from 5 months in Group 2 to 2 months
      in Group 1. Hepatitis B-containing combination vaccines should reduce the number
      of vaccine injections required in childhood and maintain excellent seroprotection
      against multiple pathogens.

PMID- 12192168
TI  - Peripheral blood eosinophilia and eosinophil accumulation in coronary
      microvessels in acute Kawasaki disease.
AB  - BACKGROUND: Early stage Kawasaki disease (KD) histopathology includes
      perivasculitis and vasculitis of the microvessels. The lesions then extend to
      larger vessels. Therefore the analysis of microvessel lesions is important to
      better understand the initial pathogenesis of KD vasculitis. METHODS AND RESULTS:
      We studied epicardial microvessel lesions (<50 microm) and aneurysm lesions of
      paraffin-embedded cardiac tissues from 4 Japanese patients who died 7 to 22 days
      after KD onset. The cellular composition in the microvessel lesions was different
      from that in coronary aneurysm lesions; eosinophils were preferentially
      accumulated in the microvessel lesions. The average population of eosinophils was
      16% of total infiltrated cells in the microvessel lesions, whereas it was 3% in
      the intima of aneurysm walls. We examined peripheral blood eosinophil cell counts
      in 95 KD patients and 95 febrile age-matched controls. Baseline eosinophil cell
      counts in KD patients were higher than those in febrile control patients (361 +/-
      441 65 +/- 133; < 0.0001). Eosinophilia (>350 cells/microl) before therapy was
      documented in 36% of KD patients, but in only 4% of febrile controls ( < 0.0001).
      Sixty-six KD patients (69%) developed eosinophilia within 2 weeks of illness.
      CONCLUSIONS: Because the numbers of circulating eosinophils in the body are
      tightly regulated, eosinophil accumulation in blood or tissues may reflect the
      host's immune response against KD related antigen(s).

PMID- 12192169
TI  - Retrospective population-based assessment of medically attended injection site
      reactions, seizures, allergic responses and febrile episodes after acellular
      pertussis vaccine combined with diphtheria and tetanus toxoids.
AB  - BACKGROUND: Since 1997 diphtheria-tetanus toxoids-acellular pertussis (DTaP)
      vaccines have been recommended for the five dose pertussis vaccination series. To
      assess rates of medically attended injection site reactions (ISRs), seizures,
      allergic responses and febrile episodes after Tripedia DTaP vaccine administered
      in the context of routine care, we conducted a retrospective assessment among the
      population of Group Health Cooperative from 1997 through 2000. METHODS:
      Administrative databases were used to identify medical visits linked with
      diagnostic codes potentially indicative of ISRs, seizures, allergic responses and
      febrile episodes after DTaP vaccine. Outcomes were confirmed by medical record
      review. RESULTS: During the study period 76 133 doses of DTaP were administered.
      Of the 26 ISRs identified, 6 followed DTaP given as the fourth dose and 18
      followed DTaP given as the fifth dose, for rates of 1 per 2779 and 1 per 900
      vaccinations, respectively. During the study period nearly all children receiving
      DTaP as the fifth dose had received whole cell pertussis vaccine for their
      primary series, and all of the fifth dose ISRs were among that group. Four of
      those reactions involved the entire upper arm. The rate of febrile seizures
      within 2 days of DTaP among children <2 years of age was 1 per 19 496
      vaccinations. CONCLUSIONS: The low rate of febrile seizures and other serious
      events confirms the safety of DTaP vaccine. The risk of medically attended ISRs
      was highest with DTaP given as the fifth dose, and whole arm reactions were
      reported, but medically attended ISRs were relatively uncommon and were self
      limited.

PMID- 12192170
TI  - Atovaquone/proguanil for plasmodium falciparum malaria.

PMID- 12192172
TI  - Report of the working groups of the First World Congress of Pediatric
      Gastroenterology, Hepatology, and Nutrition: A Global Plan for the Future of the
      Digestive and Nutritional Health of Children.

PMID- 12192171
TI  - Smallpox and the smallpox vaccine controversy.

PMID- 12192173
TI  - Acute and chronic hepatitis: Working Group Report of the First World Congress of
      Pediatric Gastroenterology, Hepatology, and Nutrition.

PMID- 12192174
TI  - Allergy and immunologic disease: Working Group Report of the First World Congress
      of Pediatric Gastroenterology, Hepatology, and Nutrition.

PMID- 12192175
TI  - Celiac disease: Working Group Report of the First World Congress of Pediatric
      Gastroenterology, Hepatology, and Nutrition.

PMID- 12192176
TI  - Cholestatic liver disease: Working Group Report of the First World Congress of
      Pediatric Gastroenterology, Hepatology, and Nutrition.

PMID- 12192177
TI  - Chronic diarrhea and malabsorption (including short gut syndrome): Working Group
      Report of the First World Congress of Pediatric Gastroenterology, Hepatology, and
      Nutrition.

PMID- 12192178
TI  - Functional foods and probiotics: Working Group Report of the First World Congress
      of Pediatric Gastroenterology, Hepatology, and Nutrition.

PMID- 12192179
TI  - Functional gastrointestinal disorders: Working Group Report of the First World
      Congress of Pediatric Gastroenterology, Hepatology, and Nutrition.

PMID- 12192180
TI  - Genetics of gastrointestinal and hepatobiliary disorders: Working Group Report of
      the First World Congress of Pediatric Gastroenterology, Hepatology, and
      Nutrition.

PMID- 12192182
TI  - HIV disease: Working Group Report of the First World Congress of Pediatric
      Gastroenterology, Hepatology, and Nutrition.

PMID- 12192181
TI  - Helicobacter pylori infection in children and adolescents: Working Group Report
      of the First World Congress of Pediatric Gastroenterology, Hepatology, and
      Nutrition.

PMID- 12192183
TI  - Infectious diarrhea in children: Working Group Report of the First World Congress
      of Pediatric Gastroenterology, Hepatology, and Nutrition.

PMID- 12192184
TI  - Inflammatory bowel disease in children and adolescents: Working Group Report of
      the First World Congress of Pediatric Gastroenterology, Hepatology, and
      Nutrition.

PMID- 12192185
TI  - Liver and intestinal transplantation in children: Working Group Report of the
      First World Congress of Pediatric Gastroenterology, Hepatology, and Nutrition.

PMID- 12192186
TI  - Malnutrition and diarrhea: Working Group Report of the First World Congress of
      Pediatric Gastroenterology, Hepatology, and Nutrition.

PMID- 12192187
TI  - Metabolic liver disease: Working Group Report of the First World Congress of
      Pediatric Gastroenterology, Hepatology, and Nutrition.

PMID- 12192188
TI  - Motility disorders in childhood: Working Group Report of the First World Congress
      of Pediatric Gastroenterology, Hepatology, and Nutrition.

PMID- 12192189
TI  - New endoscopic and diagnostic techniques: Working Group Report of the First World
      Congress of Pediatric Gastroenterology, Hepatology, and Nutrition: management of
      GI bleeding, dysplasia screening, and endoscopic training--issues for the new
      millennium.

PMID- 12192190
TI  - Obesity in children and adolescents worldwide: current views and future
      directions--Working Group Report of the First World Congress of Pediatric
      Gastroenterology, Hepatology, and Nutrition.

PMID- 12192191
TI  - Pancreatic disorders and cystic fibrosis: Working Group Report of the First World
      Congress of Pediatric Gastroenterology, Hepatology, and Nutrition.

PMID- 12192192
TI  - The political environment: effects on growth and development--Working Group
      Report of the First World Congress of Pediatric Gastroenterology, Hepatology, and
      Nutrition.

PMID- 12192193
TI  - Indicting the test to acquit the tester: a pedant's viewpoint.

PMID- 12192194
TI  - Enteral access for nutritional support: rationale for utilization.
AB  - Acquisition of enteral access and provision of a sufficient volume of enteral
      nutrients early in the hospital course of a critically ill patient afford an
      opportunity to improve the outcome of that patient through the progression of his
      or her disease process. Failure to use the enteral route of feeding not only
      squanders this opportunity, but may, in addition, promote a pro-inflammatory
      state, which exacerbates disease severity and worsens morbidity. Enteral feeding
      provides a conduit for the delivery of immune stimulants and serves as effective
      prophylaxis against stress-induced gastropathy and gastrointestinal hemorrhage.
      Tube placement beyond the stomach into the small bowel in hypermetabolic,
      severely ill patients prone to ileus and disordered gut motility aids delivery of
      enteral nutrients while reducing risk of aspiration. Endoscopic skills and
      expertise in gastrointestinal physiology are vital to the success of a nutrition
      support service and the provision of enteral tube feeding.

PMID- 12192195
TI  - Chronic radiation enteritis: a ten-year follow-up.

PMID- 12192196
TI  - Endoscopic injection with fibrin sealant versus epinephrine for arrest of peptic
      ulcer bleeding: a randomized, comparative trial.
AB  - BACKGROUND: endoscopic epinephrine and fibrin injection in the treatment of
      bleeding peptic ulcer are reported to be safe, effective, and easy to use.
      However, a wide range of rebleeding rates has been reported with epinephrine
      injection. GOALS: to compare the hemostatic effects of endoscopic injection with
      fibrin sealant versus epinephrine. STUDY: between December 1998 and July 2000, 51
      patients with active bleeding or nonbleeding visible vessels entered this trial.
      The clinical parameters were comparable between both groups. In the epinephrine
      group, we injected 5 to 10 mL of 1:10,000 epinephrine, surrounding the bleeder.
      In the fibrin sealant group, we injected fibrin sealant 4 mL, surrounding the
      bleeder. RESULTS: initial hemostasis was obtained in all enrolled patients.
      Rebleeding was more in the epinephrine group than in the fibrin sealant group (4
      [15%] of 26 vs. 14 [56%] of 25, = 0.003 on the intention-to-treat basis, and 4
      [16.7%] of 24 vs. 14 [58.3%] of 24, = 0.003 on the per protocol basis,
      respectively). Volume of blood transfusion, number of surgeries, hospital stay,
      and number of deaths were similar between both groups. CONCLUSION: fibrin sealant
      injection is more effective in preventing rebleeding than epinephrine after
      endoscopic therapy, but this study showed no difference in outcomes with either
      therapy.

PMID- 12192197
TI  - Endoscopic sclerotherapy of gastric variceal bleeding with N-butyl-2
      cyanoacrylate.
AB  - BACKGROUND: bleeding from gastric varices is a life-threatening complication of
      portal hypertension. Fundal and isolated gastric varices are at high risk for
      variceal bleeding. In this study, we report our experience with n-butyl-2
      cyanoacrylate (BC) in patients with large gastric varices. STUDY: twenty-nine
      patients (15 male, 14 female) with large fundal varices (active bleed, 5; passive
      bleed after eradication of esophageal varices, 13; unbled fundal varices with red
      color sign, 11) underwent endoscopic sclerotherapy with BC. Cirrhosis was present
      in 13 patients; extrahepatic portal venous obstruction, in 13; and noncirrhotic
      portal fibrosis, in 3. N-Butyl-2-cyanoacrylate after mixing with lipiodol (1:1)
      was given to the initial 10 patients and was given in undiluted form to the
      remaining patients, followed by injection of 0.7 mL of distilled water to rinse
      the injection catheter. One to three injections (0.5-1 mL) were given until all
      gastric varices became hard. All patients were on long-term endoscopic
      sclerotherapy or variceal ligation programs for eradication of esophageal
      varices. RESULTS: acute variceal bleeding was controlled in all five patients
      with BC injections. Eradication of gastric varices was achieved in 27 (93.1%)
      patients (20 patients in 1 session, 4 patients in 2, and 3 patients in 3-6).
      Rebleeding occurred in three (10.3%) patients who responded to repeat BC
      injections. Complications related to the procedure occurred in two (6.9%)
      patients. In one patient, the needle became impacted into the tissue adhesive.
      This patient died 5 days later because of massive upper gastrointestinal
      bleeding. In the other patient, there was distal embolization. CONCLUSIONS:
      sclerotherapy of gastric varices with BC is a safe and an effective treatment for
      control of bleeding and eradication. The needle should be withdrawn immediately
      after the BC injection to prevent its impaction into the tissue adhesive.

PMID- 12192198
TI  - A controlled, prospective screening study of celiac disease presenting as iron
      deficiency anemia.
AB  - BACKGROUND: anemia is the most frequent presenting feature of celiac disease in
      adults using endomysial antibody (EmA) screening. Endomysial antibody screening
      of anemia may allow detection of celiac disease at an earlier stage of
      investigation and after a shorter duration of symptoms. The characteristics of
      celiac patients identified by screening require further study. GOALS: a goal of
      this study was to evaluate the prevalence of celiac disease in adult patients
      with iron deficiency anemia compared with a nonanemic control population using
      immunoglobulin A (IgA) EmA screening. We also studied the positive predictive
      value (PPV) of the EmA assay and correlated the severity of histologic
      abnormalities in distal duodenal biopsy samples with EmA and tissue
      transglutaminase (tTG) antibody titer. STUDY: four hundred eighty-four patients
      with microcytic, hypochromic anemia underwent IgA EmA assay. Four hundred ninety
      eight nonanemic age- and sex-matched patients from the same source comprised the
      control group. Patients with positive serology results were invited for
      endoscopic duodenal biopsies. RESULTS: one in 44 anemic patients was diagnosed
      with histologically confirmed celiac disease compared with one in 498 nonanemic
      patients ( < 0.01). Fifty percent of women were premenopausal, and 25% of
      patients were older than 65 years. The PPV for EmA assay varied between 73% and
      93% for anemic patients and improved at higher antibody titer, with all false
      positive results occurring at the lowest titers. CONCLUSIONS: screening for
      celiac disease using IgA EmA assay is effective in anemic patients, including
      premenopausal women and patients older than 65 years, and it can be recommended
      in clinical practice.

PMID- 12192200
TI  - Determination of thiopurine methyltransferase genotype or phenotype optimizes
      initial dosing of azathioprine for the treatment of Crohn's disease.
AB  - BACKGROUND: although azathioprine (AZA) is an effective immunomodulator in
      treating Crohn's disease, some patients develop leukopenia and risk severe
      infections. Thiopurine methyltransferase (TPMT) is an enzyme responsible for the
      metabolism of AZA, and its activity is inversely related to the risk of
      developing acute leukopenia. GOALS: the aim of this retrospective study is to
      determine whether initial AZA dosing based on TPMT genotype or phenotype alters
      the likelihood of developing acute leukopenia. STUDY: between January 2000 and
      February 2001, 71 patients with Crohn's disease considered for AZA therapy and
      with a recorded TPMT genotype or phenotype were identified using a comprehensive
      text-oriented database at the University of Pittsburgh Medical Center,
      Presbyterian Hospital, Pittsburgh, PA. The baseline demographics, TPMT genotype
      or phenotype, initial dose of oral AZA, subsequent white blood counts, and
      complications that necessitated discontinuation of therapy were evaluated.
      RESULTS: of the 63 patients with normal TPMT activity, 45 were started on 2 to
      2.5 mg/kg/d of AZA, seven received doses less than 2 mg/kg/d, and 11 did not
      start AZA. Of the eight patients with intermediate TPMT activity, seven were
      started on 1 to 1.5 mg/kg/d of AZA, and one did not receive treatment. None of
      the patients that received AZA developed acute leukopenia (< 3,000/mm ).
      CONCLUSIONS: patients with Crohn's disease and normal TPMT activity who were
      started on high-dose AZA (2-2.5mg /kg/d) and patients with intermediate enzyme
      activity who were started on reduced doses of AZA did not develop acute
      leukopenia.

PMID- 12192199
TI  - In diffuse atrophic gastritis, routine histology underestimates Helicobacter
      pylori infection.
AB  - BACKGROUND: histologic detection of shows high diagnostic accuracy in chronic
      nonatrophic gastritis. However, when atrophy occurs, the sensitivity of bacterial
      detection varies. This study assessed the routine histologic sensitivity for
      current infection in patients with atrophic gastritis, with and without
      intestinal metaplasia. STUDY: five hundred and ten consecutive patients with
      diffuse chronic atrophic gastritis, with (174 cases) and without (336 cases)
      intestinal metaplasia, were investigated following the Sydney System
      recommendations. In cases with negative tissue staining for Helicobacter-like
      organisms, serum immunoglobulin G (IgG) antibodies to were assayed. RESULTS: the
      overall rate of positive staining for Helicobacter-like organisms was 51.8% (264
      of 510 cases), 62.8% and 30.4% in cases without and with intestinal metaplasia,
      respectively. Serum IgG antibody determination was consistent with current
      infection in 180 (73.2%) of the 246 cases with negative histology. detection rate
      was significantly lower ( < 0.01) in Grade 3 than in Grade 1 atrophy. When
      intestinal metaplasia was present, histologic bacterial detection progressively
      decreased, from 46.3% to 20%, depending on severity. infection was found by
      histology in 42.2% and in 56.2% of cases with inactive and active disease,
      respectively. Overall, the diagnostic accuracy of histology was significantly
      lower ( <0.001) than that of histology combined with serology. CONCLUSIONS: most
      (87.1%) diffuse chronic atrophic gastritis patients showed serum antibody IgG
      levels consistent with current infection, although histology was positive in only
      59.5% of cases. Gastritis activity and current infection did not ever correlate
      in the presence of mucosal atrophy and/or intestinal metaplasia. Routine biopsy
      sampling, hematoxylin and eosin staining, and Giemsa staining therefore
      underestimated the true prevalence of infection.

PMID- 12192201
TI  - Thyroid-related autoantibodies and celiac disease: a role for a gluten-free diet?
AB  - An association between celiac disease and other autoimmune disorders--such as
      insulin-dependent diabetes, Addison's disease, systemic lupus erythematous,
      rheumatoid arthritis, alopecia areata, and autoimmune endocrine diseases--has
      been described. The aim of this study was to evaluate the prevalence of celiac
      disease in 100 patients with autoimmune thyroid disease. Moreover, the monitoring
      of patients with concomitant celiac and autoimmune thyroid diseases, after a
      gluten-free diet or a gluten-containing diet, can give important insights into
      the effect of dietary habits in thyroid autoantibodies modulation. In our study,
      the prevalence of celiac disease in patients with autoimmune thyroid disease was
      2%. In these two celiac patients, the serologic markers became undetectable 6
      months after beginning a gluten-free diet. However, thyroid autoantibodies did
      not positively correlate with dietary habits.

PMID- 12192202
TI  - Gastric carcinoids in a patient with pernicious anemia and familial adenomatous
      polyposis.
AB  - Familial adenomatous polyposis (FAP) is associated with upper gastrointestinal
      adenomas and adenocarcinomas. A carcinoid tumor in the base of a duodenal adenoma
      in a patient with FAP was documented only once before. We report a patient with
      FAP who has multiple gastric carcinoids plus pernicious anemia as a coexisting
      disease. Genetic analysis and studies of other FAP patients are necessary to
      establish whether an association exists between FAP and carcinoid tumors. Optimal
      management of this type of gastric carcinoid is uncertain.

PMID- 12192203
TI  - Management of nonalcoholic steatohepatitis: an analytic review.
AB  - Nonalcoholic steatohepatitis (NASH) is a metabolic disorder of the liver, which,
      although usually relatively mild, may in some cause fibrosis, cirrhosis, and
      premature death resulting from liver failure. Its prevalence is increasing, and
      it is probably underestimated as a cause for cirrhosis. The need for an effective
      treatment is clear and urgent. Although several small, pilot, and randomized
      studies have been reported, large-scale studies are yet to be performed in
      patients with NASH. The aim of therapy is to intervene early in patients at risk
      of progression of liver disease. In this review, we summarize the extant
      literature on the management of NASH and discuss the potential future therapies
      and prophylactic recommendations in patients with NASH.

PMID- 12192204
TI  - Macroscopic and microscopic findings of livers in malignant hematologic
      disorders, biopsied under peritoneoscopy.
AB  - It is important to detect liver involvement in extranodal lesions in malignant
      hematologic disorders to make accurate diagnoses and estimate their clinical
      stage. We report seven cases of malignant lymphoma and a case of histiocytosis X.
      All patients expressed positive C-reactive protein and a high erythrocyte
      sedimentation rate, and a high serum value of alkaline phosphatase or lactic
      dehydrogenase was seen. Image analyses revealed enlarged livers without any space
      occupying lesions. Peritoneoscopy with liver biopsy showed a diffuse presence of
      white maculae or peliosis hepatis on the liver surface among all the patients,
      and granulomas with or without malignant cells were observed histologically and
      congestion was seen in the lobules. Thus, peritoneoscopy with liver biopsy
      appears to be a useful tool not only to detect early liver involvement in
      malignant hematologic disorders but also to make their accurate diagnosis.

PMID- 12192205
TI  - Rising prevalence of hepatitis C virus infection among patients recently
      diagnosed with hepatocellular carcinoma in the United States.
AB  - BACKGROUND: the aim of this study was to determine whether hepatitis C virus
      (HCV) is an underlying cause of the increase in the incidence of hepatocellular
      carcinoma (HCC) in the United States. STUDY: the medical records of all patients
      who had received a pathologic diagnosis of HCC at the University of Texas M.D.
      Anderson Cancer Center, Houston, Texas, U.S.A., during 1993 through 1998 were
      reviewed. Only patients residing in the United States were analyzed. All patients
      were tested for HCV and hepatitis B virus serologic markers. RESULTS: the number
      of patients with HCC referred to M.D. Anderson Cancer Center increased from 143
      in 1993 through 1995 to 216 in 1996 through 1998. Twenty-six patients (18%) and
      66 patients (31%) with anti-HCV antibodies were diagnosed with HCC from 1993 to
      1995 and from 1996 to 1998, respectively, thus constituting a significant
      increase ( = 0.01). Although the age distribution of these patients did not
      differ significantly between 1993 to 1995 and 1996 to 1998, the increase in HCV
      associated HCC was greatest among patients 40 to 49 years old. Hepatitis B
      surface antigens (HBsAg) or anti-hepatitis B core antigens were found in 37
      patients (26%) with HCC during 1993 to 1995 and in 37 patients (17%) with HCC
      during 1996 to 1998 ( = 0.06). Moreover, a significant decrease in the prevalence
      of HBsAg from 1996 to 1998 (21 patients; 10%) compared with 1993 to 1995 (25
      patients; 18%) was observed ( = 0.03). CONCLUSION: hepatitis C infection is the
      major viral factor contributing to the increase in HCC incidence observed in this
      large-scale, single-center United States-based experience.

PMID- 12192206
TI  - Mirtazapine-induced hepatotoxicity.
AB  - We report two cases of hepatotoxicity induced by mirtazapine. Two women treated
      for depression with mirtazapine developed severe hepatotoxicity because of the
      drug. In the first case, mirtazapine was prescribed for 3 years and the patient
      developed derangement in liver function with prolonged jaundice, which improved
      after the withdrawal of mirtazapine. The use of mirtazapine in the second case
      was associated with prolonged jaundice, which only recovered 3 months after the
      withdrawal of mirtazapine. The cause of mirtazapine-induced liver toxicity was
      unknown, and to our knowledge, these are the first reported cases of mirtazapine
      induced prolonged jaundice.

PMID- 12192207
TI  - Recombinant interferon alfa 2b therapy in a patient with metastatic
      hepatocellular carcinoma.
AB  - At present, there is no effective treatment of metastatic hepatocellular
      carcinoma (HCC). Systemic interferon alfa (IFN-alpha) was found to be of some use
      in patients with inoperable HCC in two randomized trials. We report a case in
      which metastatic HCC was cured by systemic IFN-alpha 2b in combination with
      surgery. A patient developed two bilateral pulmonary metastatic HCC nodules 5
      months after the resection of the primary HCC. He was treated with systemic IFN
      alpha 2b. One lesion completely disappeared. The other lesion showed an initial
      response but became resistant to the IFN-alpha 2b therapy after reduction in
      dosage because of the side effects. This was resected in view of the absence of
      new metastases after 9 months of IFN-alpha 2b therapy. He remained free from
      recurrence at 59 months of follow-up. A rare, but reversible, complication of
      retinal cotton wool spots caused by IFN-alpha 2b occurred in this patient. IFN
      alpha 2b is partially effective in treating metastatic HCC. The time for its
      administration can also serve as an observation period, which is vital in
      deciding whether definitive surgical treatment of any residual lesions is
      indicated.

PMID- 12192208
TI  - Liver transplantation in mushroom poisoning.
AB  - Liver transplantation plays an important role in the treatment of patients with
      fulminant hepatic failure (FHF). Early determination of prognosis in cases of FHF
      is important to allow prompt decision-making regarding the need for liver
      transplantation. Mushroom poisoning is a rare cause of FHF, and as a result,
      prognostic criteria are not well recognized. It appears that the severity of
      coagulopathy and encephalopathy predicts a poor outcome, whereas the degree of
      bilirubin elevation may not. We present a case of FHF related to mushroom
      poisoning that required liver transplantation. The clinical presentation, medical
      management, and prognostic criteria in mushroom poisoning are discussed.

PMID- 12192209
TI  - Urticarial vasculitis with asymptomatic chronic hepatitis C infection: response
      to doxepin, interferon-alfa, and ribavirin.

PMID- 12192210
TI  - Various sarcoid lesions in a patient induced by interferon therapy for chronic
      hepatitis C.

PMID- 12192211
TI  - Superior mesenteric arteriovenous fistula: a rare cause of esophageal variceal
      bleeding.

PMID- 12192213
TI  - Therapeutic efficacy of hyperbaric oxygenation in ulcerative colitis refractory
      to medical treatment.

PMID- 12192212
TI  - A case of primary follicular lymphoma in the duodenum confined to the mucosal
      layer.

PMID- 12192214
TI  - Digital rectal self-examination in the diagnosis of colorectal cancer.

PMID- 12192215
TI  - On the death of a manuscript.

PMID- 12192216
TI  - Cultural literacy and health.

PMID- 12192217
TI  - Whad'ya know? Another view on cultural literacy.

PMID- 12192218
TI  - Validation studies: bias, efficiency, and exposure assessment.

PMID- 12192219
TI  - The performance of methods for correcting measurement error in case-control
      studies.
AB  - BACKGROUND: It is generally agreed that adjustment for measurement error (when
      feasible) can substantially increase the validity of epidemiologic analyses.
      Although a broad variety of methods for measurement error correction has been
      developed, application in practice is rare. One reason may be that little is
      known about the robustness of these methods against violations of their
      restrictive assumptions. METHODS: We carried out a simulation study to assess the
      performance of two error correction methods (a regression calibration method and
      a semiparametric approach) as compared with standard analyses without measurement
      error correction in case-control studies with internal validation data.
      Performance was assessed over a wide range of model parameters including varying
      degrees of violations of assumptions. RESULTS: In nearly all the settings
      assessed, the semiparametric estimate performed better than all alternatives
      under investigation. The regression calibration method is sensitive to violations
      of the assumptions of nondifferential error and small error variance.
      CONCLUSIONS: The semiparametric method is a very robust method to correct for
      measurement error in case-control studies, but lack of functional software
      hinders widespread use. If the assumptions for the regression calibration method
      are fulfilled, application of this method, originally developed for cohort
      studies, in case-control studies may be a useful alternative that is easy to
      implement.

PMID- 12192220
TI  - Household firearm ownership and suicide rates in the United States.
AB  - BACKGROUND: In the United States, more people kill themselves with firearms than
      with all other methods combined. A central question regarding the relation
      between firearms and suicide is whether the ready availability of firearms
      increases the suicide rate, rather than merely increasing the proportion of
      suicides from guns. METHODS: We used publicly available data for the nine regions
      and 50 states in the United States over a 10-year period (1988-1997) to examine
      the association between levels of household firearm ownership and rates of
      suicide, firearm suicide, and non-firearm suicide by age groups and gender.
      RESULTS: In both regional and state-level analyses, for the U.S. population as a
      whole, for both males and females, and for virtually every age group, a robust
      association exists between levels of household firearm ownership and suicide
      rates. CONCLUSIONS: Where firearm ownership levels are higher, a
      disproportionately large number of people die from suicide.

PMID- 12192221
TI  - Air bags and passenger fatality according to passenger age and restraint use.
AB  - BACKGROUND: Some children have been killed by air bags, leading to advice that
      young children should not sit in front of an active air bag. METHODS: We
      conducted a case-control study to estimate the association of passenger air bag
      presence with death, according to passenger age and seat belt use. We used data
      from crashes on U.S. public roads in 1992 through 1998. Cases (N = 20,987) were
      front seat passengers who died, and controls (N = 69,277) were a sample of
      survivors. RESULTS: Among restrained passengers, the adjusted relative risk of
      death for those with a passenger air bag was 0.79 (95% confidence interval [CI] =
      0.66-0.94); for children 12 years or younger, the adjusted relative risk was 1.04
      (0.65-1.67) [corrected], and for adults 20 years or older it was 0.75 (0.62-0.91)
      [corrected]. Among unrestrained passengers, the adjusted relative risk was 1.03
      (CI = 0.81-1.30); for children 12 years or younger the adjusted relative risk was
      1.37 (0.84-2.21) [corrected], and for adults 20 years or older it was 0.96 (0.75
      1.24). CONCLUSIONS: Passenger air bags may be a hazard to unrestrained children
      and of little benefit to unrestrained adults. Our results support the advice that
      children younger than 13 years should not sit in front of an active air bag.

PMID- 12192222
TI  - Determinants of co-colonization with group B streptococcus among heterosexual
      college couples.
AB  - BACKGROUND: Group B causes morbidity and mortality among newborns, pregnant
      women, and nonpregnant adults. Among adults, sexual and fecal-oral routes of
      transmission are hypothesized; this study addresses whether sexual transmission
      occurs. METHODS: Our outcome of interest was group B. From our investigation of
      the heterosexual transmission of urinary tract infections among college students
      at the University of Michigan, conducted in 1996-1999, we identified 120 couples
      in which one or both partners carried group B. Each partner completed a
      questionnaire regarding potential risk factors for colonization. RESULTS: Co
      colonization with the identical group B strain (as determined by pulsed-field gel
      electrophoresis) occurred in 86% of the 57 co-colonized couples. When the male
      sex partner carried group B, 64% of female partners also were colonized;
      conversely, 49% of male partners of colonized females were colonized with
      identical strains. Among behaviors predicting co-colonization within the
      partnership, male-to-female oral sex was a risk factor among both women (odds
      ratio [OR] = 2.9; 95% confidence interval [CI] = 1.2-6.9) and men (OR = 2.5; CI =
      1.1-5.6). First sex at age 20 years or older was associated with an increased
      risk among women (OR = 2.1; CI = 0.7-6.4) and among men (OR = 3.0; CI = 1.0-9.3),
      and four or more lifetime sex partners was associated with a decreased risk of co
      colonization among women (OR = 0.6; CI = 0.2-1.5) and among men (OR = 0.4; CI =
      0.2-1.0). CONCLUSIONS: Among heterosexual college couples, sexual activity,
      particularly male-to-female oral sex, increases the risk of co-colonization with
      an identical group B strain. Future studies should evaluate the role of the
      pharynx and examine the effects of both bacterial characteristics and host
      response on transmission.

PMID- 12192223
TI  - Assessing the exposure of pregnant women to drinking water disinfection
      byproducts.
AB  - BACKGROUND: To evaluate associations between exposure to disinfection byproducts
      in drinking water and adverse birth outcomes, personal exposure to disinfection
      byproducts must take into consideration multiple routes of exposure. METHODS: We
      assessed the reproducibility and validity of a questionnaire measuring water
      consumption, showering and bathing habits, use of chlorine-based products, and
      swimming pool attendance in 237 pregnant Italian women enrolled between June and
      December 1999. The questionnaire was completed during the last trimester of
      pregnancy (preQ) and again a few days after delivery (postQ). Data from postQ
      were compared with a 7-day diary completed during the last trimester. RESULTS:
      According to postQ, total water intake was 2.6 liters per day, whereas tap water
      intake was 0.6 liters per day. Intraclass correlation coefficients of postQ
      compared with preQ were 0.85 for tap water daily intake and 0.77 for duration of
      showering and bathing. Pearson's correlation coefficients were 0.84 for tap water
      daily intake, 0.81 for frequency of showering, and 0.94 for bathing. The kappa
      statistics were 0.76 (95% confidence limits = 0.68, 0.85) for use of domestic
      chlorine-based products and 0.82 (0.70, 0.94) for indoor swimming. Pearson's
      coefficients for postQ compared with the diary were 0.78 for tap water daily
      intake, 0.62 for frequency of showering, and 0.64 for bathing. Compared with the
      diary, the sensitivity and specificity of postQ in assessing indoor swimming were
      75% and 90%, respectively. CONCLUSIONS: The questionnaire appears to be a valid
      and reliable method for assessing exposure to disinfection byproducts in the last
      trimester of pregnancy.

PMID- 12192224
TI  - Testing for candidate gene linkage disequilibrium using a dense array of single
      nucleotide polymorphisms in case-parents studies.
AB  - The future of genetic studies of complex human diseases will rely more and more
      on the epidemiologic association paradigm, in particular the use of the
      transmission/disequilibrium test to detect linkage disequilibrium in a case
      parents study. With the rapid progress in genomic studies, many single nucleotide
      polymorphisms will be identified and genotyped within a very short physical
      distance. Analyzing multiple single nucleotide polymorphisms within a candidate
      gene/region with Bonferroni correction for multiple transmission/disequilibrium
      tests will lead to a conservative test, and hence a power loss. I propose a new
      method, the "Adaptive PRIncipal COmponent Test" (APRICOT). The method has the
      following properties: (1) it does not need haplotype information; (2) it is
      nonparametric-it does not make specific assumptions about the population history
      or population structure; and (3) the calculation of the test statistic and the
      determination of its significance level are simple and straightforward. Monte
      Carlo simulation reveals that adaptive principal component test maintains the
      nominal significance level under the null hypothesis of no linkage
      disequilibrium, even under complex situations of multiple ancestral haplotypes
      and structured populations. It provides a substantial power advantage over the
      conventional Bonferroni approach. The adaptive principal component test is a
      promising method for candidate gene testing using single nucleotide
      polymorphisms.

PMID- 12192225
TI  - Cancer incidence after nasopharyngeal radium irradiation.
AB  - BACKGROUND: From 1940 until 1970, nasopharyngeal radium irradiation was used to
      treat children and military personnel suffering from Eustachian tube failure
      attributable to local lymphoid hyperplasia. METHODS: We studied cancer incidence
      in a cohort of 4339 Dutch patients treated with nasopharyngeal radium
      irradiation, mostly in childhood, and 4104 frequency-matched nonexposed subjects.
      Average doses to the nasopharynx, pituitary gland, brain, and thyroid gland were
      275, 10.9, 1.8, and 1.5 cGy, respectively. We assessed cancer incidence from
      cancer registry linkage (1989-1996), self-report including medical verification
      (1945-1988), and death certificates (1945-1996). RESULTS: During 18-50 years of
      follow-up, four thyroid malignancies (standardized incidence ratio [SIR] = 2.8;
      95% confidence interval [CI] = 0.8-7.2) and five malignant brain tumors (SIR =
      1.3; CI = 0.4-3.1) were observed. Increased risks were observed for malignancies
      of lymphoproliferative and hematopoietic origin (SIR = 1.9; CI = 1.2-2.8) and
      breast cancer (SIR = 1.5; CI = 1.1-2.1). Strong dose-response trends could not be
      demonstrated for any cancer outcome, although relative risk estimates were
      elevated in the highest-dose category for head and neck cancer and breast cancer.
      CONCLUSIONS: These data provide little evidence for a high excess risk of cancer
      associated with nasopharyngeal radium irradiation treatment as applied in the
      Netherlands. Inconsistent findings across studies and public concern warrant the
      continuing follow-up of available cohorts.

PMID- 12192226
TI  - Does exercise reduce inflammation? Physical activity and C-reactive protein among
      U.S. adults.
AB  - BACKGROUND: Physical activity may lower the risk for coronary heart disease by
      mitigating inflammation, which plays a key role in the pathophysiology of
      atherosclerosis. The purpose of this study was to examine the association between
      physical activity and C-reactive protein concentration in a national sample of
      the U.S. population. METHODS: The analytic sample included 13,748 participants
      >or=20 years of age in the National Health and Nutrition Examination Survey III
      (1988-1994) with complete data for the main study variables. RESULTS: After
      adjusting for age, sex, ethnicity, education, work status, smoking status,
      cotinine concentration, hypertension, body mass index, waist-to-hip ratio, high
      density lipoprotein cholesterol concentration, and aspirin use, the odds ratios
      for elevated C-reactive protein concentration (dichotomized at the >or=85th
      percentile of the sex-specific distribution) were 0.98 (95% confidence interval =
      0.78-1.23), 0.85 (0.70-1.02), and 0.53 (0.40-0.71) for participants who engaged
      in light, moderate, and vigorous physical activity, respectively, during the
      previous month compared with participants who did not engage in any leisure-time
      physical activity. In addition, leisure-time physical activity was positively
      associated with serum albumin concentration and inversely associated with both
      log-transformed plasma fibrinogen concentration and log-transformed white blood
      cell count. CONCLUSIONS: These results add to mounting evidence that physical
      activity may reduce inflammation, which is a critical process in the pathogenesis
      of cardiovascular disease.

PMID- 12192227
TI  - Birth weight and perinatal mortality: a comparison of "optimal" birth weight in
      seven Western European countries.
AB  - BACKGROUND: Previous studies have suggested that a population's entire birth
      weight distribution may be shifted towards higher or lower birth weights, and
      that optimal birth weight may be lower in populations with a lower average birth
      weight. We evaluated this hypothesis for seven western European countries.
      METHODS: We obtained data on all singleton births (N = 1,372,092) and extended
      perinatal deaths (stillbirths plus neonatal deaths; N = 7,900) occurring in
      Finland, Sweden, Norway, Denmark, Scotland, the Netherlands, and Flanders
      (Belgium) in 1993-1995. We assessed whether countries differed in the mode of
      their birth weight distribution and in the birth weight associated with the
      lowest perinatal mortality, and then correlated the two. RESULTS: Substantial
      international differences were found in the mode of the birth weight
      distribution, which ranged between 3384 gm in Flanders and 3628 gm in Finland.
      The position of the minimum of the perinatal mortality curve also differed
      considerably, ranging between 3755 gm in Flanders and 4305 gm in Norway. There
      was a strong relation between the two: for every 100 gm increase in modal birth
      weight, optimal birth weight was 170 gm higher (95% confidence interval = 104-236
      gm). CONCLUSIONS: Our results confirm those of previous studies that compared two
      populations. To improve the identification of small babies at high risk of
      perinatal death, population-specific standards for birth weight should be
      developed and used.

PMID- 12192228
TI  - Maternal vitamin use and reduced risk of neuroblastoma.
AB  - BACKGROUND: Previous studies have suggested that maternal vitamin use during
      pregnancy may reduce the incidence of childhood brain tumors. Using data from a
      large North American study, we conducted an analysis to investigate maternal
      vitamin use and neuroblastoma in offspring. METHODS: Cases were children
      diagnosed with neuroblastoma over the period 1 May 1992 to 30 April 1994 at
      Children's Cancer Group and Pediatric Oncology Group institutions throughout the
      United States and Canada. One matched control was selected for each case using
      random-digit dialing. We obtained vitamin use information during specific periods
      before and during pregnancy from 538 case and 504 control mothers through
      telephone interviews. RESULTS: Daily vitamin and mineral use in the month before
      pregnancy and in each trimester was associated with a 30-40% reduction in risk of
      neuroblastoma. For example, daily use in the second trimester had an odds ratio
      of 0.6 (95% confidence interval = 0.4-0.9). We were unable to isolate the effects
      of specific vitamins or minerals. Neither age at diagnosis nor oncogene
      amplification status materially altered the results. CONCLUSIONS: The results of
      this study suggest that vitamin use during pregnancy might reduce incidence of
      neuroblastoma, consistent with findings for other childhood cancers.

PMID- 12192229
TI  - Injectable hormone contraception and bone density: results from a prospective
      study.
AB  - BACKGROUND: Depot medroxyprogesterone acetate (DMPA) injectable contraception may
      decrease bone density and increase the risk for osteoporosis in later life.
      Prospective data are scarce, especially of the effects of DMPA discontinuation on
      bone. METHODS: Between 1994 and 1999, we conducted a population-based prospective
      cohort study among women enrollees of a Washington State health maintenance
      organization. We enrolled 457 nonpregnant women, ages 18-39 years (183 DMPA users
      and 274 non-users). Bone density was measured by dual-energy x-ray absorptiometry
      every 6 months for 3 years. RESULTS: Bone density decreased notably among DMPA
      exposed women at the spine (adjusted mean bone density was -0.0053 gm/cm for DMPA
      users compared with +0.0023 gm/cm for non-users for each 6-month interval) and
      total hip (-0.0060 compared with -0.0002 gm/cm ). This represents an annualized
      mean rate of change at the spine of -0.87% compared with +0.40% and, at the hip, 
      1.12% compared with -0.05%. Discontinuers of this method (N = 110) showed sizable
      increases in bone density over comparison women (for each 6-month interval,
      adjusted mean spine bone density was +0.0067 gm/cm compared with +0.0023 gm/cm,
      respectively; adjusted mean hip bone density was +0.0035 compared with -0.0002
      gm/cm ). Estimated annualized mean rates of change were +1.41% compared with
      +0.40% [corrected] at the spine and +1.03% [corrected] compared with -0.05% at
      the hip. After 30 months, mean bone density for discontinuers was similar to that
      of non-users. CONCLUSIONS: In this study, DMPA use was strongly associated with
      bone density loss. Substantial postdiscontinuation recovery of bone provides
      evidence that the effects may be largely reversible.

PMID- 12192230
TI  - Cardiovascular damage by airborne particles: are diabetics more susceptible?
AB  - BACKGROUND: Convincing evidence now exists that particulate air pollution
      exacerbates heart and lung disease, leading to increased morbidity and mortality.
      The populations particularly susceptible to these exposures are still unclear.
      Recent work on potential mechanisms of action of particulate air pollution point
      to pathways also influenced by diabetes. METHODS: We examined effect modification
      by concurrent diagnosis of diabetes overall and by age group in a hierarchical
      model for four U.S. cities. In the first stage, separate Poisson regressions were
      fit in each city and within each stratum of age and diabetes. In the second
      stage, the estimated effect size for PM (particulate air matter with aerodynamic
      diameter less than 10 microns) within city and strata was regressed against the
      stratification variables, allowing for a random effect. We used Medicare data for
      Chicago, IL, Detroit, MI, Pittsburgh, PA, and Seattle, WA, for the years 1988
      1994. RESULTS: We found that diabetics have double the risk of a PM10 -associated
      cardiovascular admission compared with nondiabetics. We also found that persons
      75 years of age and older had higher risk, and that the interaction between the
      two categories (diabetes and age) was less than additive. If the latter is
      confirmed, it may represent a survivor effect among diabetes, enhanced
      susceptibility among nondiabetics, or both. CONCLUSIONS: We conclude that
      diabetics are a population that is particularly susceptible to cardiovascular
      damage by airborne particles.

PMID- 12192231
TI  - Foodborne illness--old problem, new relevance.

PMID- 12192233
TI  - Growth in girls exposed in utero and postnatally to polybrominated biphenyls and
      polychlorinated biphenyls.

PMID- 12192234
TI  - Acetaminophen and upper gastrointestinal complications.

PMID- 12192235
TI  - Statins and cancer: will we ever know the answer?

PMID- 12192237
TI  - Epithelial ovarian carcinoma and fertility of parents.

PMID- 12192236
TI  - Epithelial ovarian carcinoma and fertility of parents.

PMID- 12192238
TI  - Passive and active smoking as possible confounders in studies of breast cancer
      risk.

PMID- 12192239
TI  - Computational realization of period analysis for monitoring cancer patient
      survival.

PMID- 12192240
TI  - Lack of referral bias in genetic studies of prostate cancer.

PMID- 12192241
TI  - How much of the decline in sperm counts can be explained by relaxed reproductive
      selection?

PMID- 12192243
TI  - Update on complement in the pathogenesis of systemic lupus erythematosus.
AB  - Complement is involved in inflammation and in the optimization of adaptive
      responses. Abnormalities in the complement system have been associated with
      autoimmunity, especially systemic lupus erythematosus. A paradoxic relation exits
      between complement and lupus. Complement-mediated tissue damage is accepted as a
      mechanism in disease pathophysiology. Conversely, complement exerts a protective
      effect in disease development. The theoretic framework explaining this protective
      influence involves the adequate disposal of apoptotic material by classic pathway
      components. Inadequate clearance of apoptotic material may evoke a
      proinflammatory autoimmune response. This conceptual model is substantiated by
      studies indicating that complement receptor genes are within major susceptibility
      loci of systemic lupus erythematosus, that functional and structural
      abnormalities in these receptors are found in lupus mouse models, and that
      genetic polymorphism of lectin pathway genes correlates with increased risk of
      disease development. Finally, new diagnostic and therapeutic modalities based on
      complement regulation have been described in the past year.

PMID- 12192245
TI  - Regulation of the vasculature: clues from lupus.
AB  - Blood vessel homeostasis involves a complex interplay between inflammatory
      signals, hormones, and other mediators. Recent research suggests that although
      atherosclerosis is primarily a problem of impaired lipid regulation, the very
      processes of cholesterol and triglyceride metabolism are intrinsically tied to
      inflammatory and hormonal regulatory signals. Similarities between inflammatory
      and endocrine disturbances in systemic lupus and the predicted consequences for
      vascular regulation help explain the high incidence of premature atherosclerosis
      in lupus. Atherosclerosis in systemic lupus, then, may be a consequence of
      imbalances in what are intrinsic homeostatic mechanisms, rather than a result of
      externally superimposed pathologic changes.

PMID- 12192244
TI  - Mediators of injury in lupus nephritis.
AB  - Systemic lupus erythematosus (SLE) is a prototypic autoimmune disease
      characterized by the production of autoantibodies and the development of immune
      complex glomerulonephritis. Lupus nephritis (LN) remains a leading cause of
      morbidity and mortality in SLE. As a result, defining pathogenetic mediators in
      LN remains a major research effort. Progression to LN in SLE is dependent on the
      host breaking immune tolerance and forming autoantibodies that deposit in the
      kidney. A variety of predisposing factors in the host must then be present for
      this event to result in renal pathology. In this article, the authors review
      recent reports that advance our understanding of LN disease mediators, from
      autoantibody production and immune complex deposition to end stage fibrosis.

PMID- 12192246
TI  - Cognitive dysfunction in neuropsychiatric systemic lupus erythematosus.
AB  - Neuropsychiatric syndromes associated with systemic lupus erythematosus are
      common, but diverse in etiology and presentation. Cognitive dysfunction is
      prevalent among these syndromes, but exhibit a significant degree of
      heterogeneity both within and between patient variability. Earlier studies of SLE
      associated cognitive dysfunction addressed its identification and description.
      Common associations were repeatedly acknowledged, including concomitant or past
      neuropsychiatric disease, use of corticosteroids, disease activity, emotional
      disturbance, and antiphospholipid antibodies. The past several years have focused
      more on elucidating the relative strengths of various risk associations, patterns
      of cognitive abnormalities, both cross-sectionally and longitudinally (, clinical
      course), and novel means to identify cognitive impairment, both functionally and
      biologically.

PMID- 12192247
TI  - Novel therapeutic agents for systemic lupus erythematosus.
AB  - The last significant breakthrough in the treatment of systemic lupus
      erythematosus (SLE) was the use of cyclophosphamide and methylprednisolone in the
      treatment of lupus nephritis. Recent advances in immunology, oncology, and
      endocrinology have resulted in many potential therapies for SLE. These therapies
      include new immunosuppressants, biologic medications, tolerizing agents,
      immunoablation techniques, and hormonal medications. Each of these approaches
      will be discussed in this review. Some therapies are currently in use in clinical
      rheumatology practice (mycophenolate mofetil) and others are entering phase I
      trials (anti-BLyS monoclonal antibody). While some of these new therapies target
      specific inflammatory mechanisms in SLE (anti-CD40L monoclonal antibody), others
      work by nonspecific inhibition of the immune system (immunoablation).

PMID- 12192248
TI  - Systemic lupus erythematosus: a blissless disease of too much BLyS (B lymphocyte
      stimulator) protein.
AB  - B lymphocyte stimulator (BLyS) protein is among the novel tumor necrosis factor
      (TNF) ligands and receptor superfamily members recently described. BLyS protein
      can promote B cell survival, expansion, and differentiation both and.
      Constitutive overexpression of BLyS protein can result in systemic lupus
      erythematosus (SLE)-like disease in mice, and circulating levels of BLyS protein
      are elevated in a subset of human SLE patients. Treatment of SLE mice with a BLyS
      protein antagonist ameliorates disease progression and enhances survival. By
      inference, BLyS protein may also play an important contributory role in
      pathogenesis and/or propagation of human SLE and becomes a legitimate candidate
      target for antagonist biologic agents.

PMID- 12192251
TI  - Hip disease in juvenile rheumatoid arthritis.
AB  - In contrast to adult rheumatoid arthritis, hips are commonly affected joints in
      severe, destructive, juvenile rheumatoid arthritis (JRA). Hip disease develops in
      30 to 50% of children with JRA. Because of the importance of the hip joint in
      weight bearing the advent of hip disease in a child with JRA warns of future
      disability [1, 2]. The challenges for the clinician are to prevent significant
      hip involvement, to halt further damage when hip disease is noted, and in the
      event that conservative treatment fails, to guide the child and family through
      hip arthroplasty and rehabilitation. Recent trends suggest that today's more
      aggressive treatment approach and more effective drugs are resulting in fewer
      children with JRA developing into severe hip disease requiring hip surgery.
      Similarly, with improvements in orthopedic surgery, the results of hip
      arthroplasty have improved.

PMID- 12192250
TI  - Juvenile spondyloarthropathies and related arthritis.
AB  - This article reviews recent publications related to the classification and
      treatment of juvenile spondyloarthropathies. We have included studies on adult
      onset spondyloarthropathies that are particularly relevant to childhood onset
      disease. Significant questions concerning classification of juvenile
      spondyloarthropathies remain unresolved. Diagnostic criteria that are both
      sensitive and specific for identifying undifferentiated spondyloarthropathies in
      adults have been developed, and while separate criteria have been proposed for
      juvenile onset disease, they remain to be validated. The most significant recent
      advances have occurred in the area of treatment. A small number of studies
      suggest that bisphosphonates such as pamidronate may be efficacious. Several
      studies using the TNF inhibitors infliximab and etanercept suggest that these
      agents hold great promise for ameliorating symptoms and improving function, while
      long-term effects on disease progression remain to be evaluated.

PMID- 12192252
TI  - Uveitis associated with childhood rheumatic diseases.
AB  - Optimal management of childhood rheumatic diseases requires an appreciation of
      their multisystem nature. The eye represents an important site of involvement,
      and inflammation of the uveal tract is a particularly frequent and potentially
      debilitating extra-articular feature of some childhood rheumatic diseases.
      Anterior uveitis associated with oligoarticular juvenile idiopathic arthritis is
      an especially distinctive entity. Other disorders in children, however, can be
      associated with posterior and intermediate uveal tract inflammation. The
      potentially debilitating consequences of uveitis associated with childhood
      rheumatic diseases, the inadequacies of existing therapies, and the
      immunopathogenic basis for particular forms of uveitis have prompted the use of
      immunomodulatory therapy, including new biologic agents, to treat childhood
      uveitis. This review summarizes recent contributions to the literature that help
      to clarify the spectrum of conditions associated with uveitis in children,
      consider evidence for immunopathogenic processes associated with uveitis, and
      address new approaches to therapy.

PMID- 12192253
TI  - Macrophage activation syndrome.
AB  - Macrophage activation syndrome (MAS) is a serious complication of childhood
      systemic inflammatory disorders that is thought to be caused by excessive
      activation and proliferation of T lymphocytes and macrophages. Recent findings in
      hemophagocytic lymphohistiocytosis, a disease that is clinically similar to MAS,
      highlight the possible pathogenetic role of a defective function of perforin, a
      protein involved in the cytolytic processes and control of lymphocyte
      proliferation. Although the clinical features of MAS have been well documented,
      early diagnosis can be difficult. Measurement of the serum ferritin level may
      assist in the diagnosis and may be a useful indicator of disease activity,
      therapy response, and prognosis. The recognition that MAS belongs to the
      secondary or reactive hemophagocytic syndromes has led to the proposal to rename
      it according to the contemporary classification of histiocytic disorders.
      Cyclosporin A has been found effective in patients with corticosteroid-resistant
      MAS. A recent report has suggested that etanercept may be a useful adjunctive
      therapeutic agent.

PMID- 12192254
TI  - Juvenile scleroderma.
AB  - Scleroderma is a relatively rare disorder in children. Among its subsets,
      localized scleroderma is more common in children than the systemic variety. No
      exciting new finding was reported in 2001 specifically applicable to childhood
      scleroderma. However, many new advances in our understanding of the growth
      factors, cytokines, and chemokines were reported. These studies should help us to
      understand the pathogenesis of early lesions of scleroderma, vascular changes,
      and fibrosis and perhaps lead us toward more rational therapy.

PMID- 12192255
TI  - Poststreptococcal reactive arthritis.
AB  - Poststreptococcal reactive arthritis (PSRA) refers to a poststreptococcal
      arthritic condition that does not fulfill the Jones Criteria for diagnosis of
      acute rheumatic fever. Clinical features include additive rather than migratory
      arthritis that responds relatively poorly to salicylates and nonsteroidals;
      persistence for mean of 2 months; elevated acute phase reactants; and laboratory
      (usually serologic) evidence of recent group A streptococcal infection. PSRA is
      not associated with HLA-B27 but rather with HLA-DRB1*01. Because up to 6% of PSRA
      patients develop mitral valve disease, it is recommended that antistreptococcal
      prophylaxis be administered for 1 year and then discontinued if there is no
      evidence of cardiac involvement.

PMID- 12192256
TI  - Panniculitis and lipodystrophy.
AB  - Panniculitis and lipodystrophy are rare disorders of subcutaneous tissue.
      Recently the incidence of lipodystrophy has been increasing secondary to its
      appearance in patients with HIV. In this population, the lipodystrophy appears to
      be a direct consequence of drug therapy. A review of the available literature
      regarding pathogenesis and treatment options is discussed. The diagnosis of
      panniculitis has been hampered by problems. The recent literature has
      concentrated on ways of improving pathologic diagnostic yields, and new aids in
      diagnosis are presented.

PMID- 12192258
TI  - Impact of osteoarthritis on individuals and society: how much disability? Social
      consequences and health economic implications.
AB  - Osteoarthritis is a major cause of disability in both the developed and
      developing world. With the population aging, the prevalence of osteoarthritis is
      increasing and its consequences are impacting significantly on society. This is
      one of the reasons why osteoarthritis has been adopted as a major focus (along
      with osteoporosis, rheumatoid arthritis, back pain, and musculoskeletal trauma)
      by the global initiative--the Decade of Bone and Joint Disease. Adequate studies
      on the costs of osteoarthritis are urgently required so that cogent arguments can
      be made to governments to appropriately fund prevention and treatment programs
      for this condition. Its recognition as a major cause of disability, particularly
      in the aging population, should increase community focus on this important
      condition.

PMID- 12192259
TI  - Roles of chondrocytes in the pathogenesis of osteoarthritis.
AB  - Recent investigations into the striking heterogeneity of cellular reaction
      patterns that are characteristic for, and puzzling in, osteoarthritic cartilage
      degeneration addressed apoptotic cell death of the chondrocytes and its
      underlying mechanisms. Also, chondrocyte senescence in terms of telomere
      reduction was reported to correlate with cartilage degeneration. Pathways of
      anabolic and catabolic activity of the cells as well as mechanisms for phenotypic
      instability of chondrocytes were further characterized. The mechanoregulation of
      the cartilage cells appears to be centrally involved in all these processes, in
      particular cell death and anabolic activity. Methodologically, the past year has
      seen the first steps of functional genomics in osteoarthritis research, providing
      new insights into the cell biology of this condition.

PMID- 12192260
TI  - Molecular markers for osteoarthritis: the road ahead.
AB  - Osteoarthritis is a disabling joint disease that is characterized by the
      progressive destruction of articular cartilage. Diagnosis is based on clinical
      symptoms in combination with radiography, which is relatively insensitive and
      provides only an indication of accumulated damage. Alternative methods, such as
      molecular markers, are therefore needed that can quantitatively, reliably, and
      sensitively detect osteoarthritic changes in the joints at an early stage of the
      disease. Such molecular markers are essential for diagnosis, prognosis, and
      monitoring of disease progression and efficacy of therapy that is targeted at
      joint destruction. In addition, these markers are important for the development
      of new disease-modifying therapies. This concise review discusses the
      developments over the past 2 years in the field of molecular markers for
      osteoarthritis.

PMID- 12192261
TI  - Imaging of the disease process.
AB  - Until recently, imaging evaluation of osteoarthritis (OA) has relied primarily on
      conventional radiography. Using radiography in clinical practice or clinical
      research, however, has been fraught with difficulty. Techniques for reproducibly
      acquiring serial radiographs of joints have improved considerably over the past
      several years. However, the greatest promise for advancing knowledge about OA and
      its treatment lies in magnetic resonance imaging (MRI) and its unique ability to
      examine the joint as a whole organ. In contrast to conventional radiography, MRI
      can directly visualize the articular cartilage, synovium, menisci, and other
      intra-articular structures important to the functional integrity of joints. There
      have been considerable advances in MRI of articular cartilage in particular over
      the past several years. However, much of this has come from small cross-sectional
      studies, and published longitudinal studies remain quite scant. The following
      discussion reviews the current status of imaging in OA and points to where
      changes might be anticipated in the future.

PMID- 12192262
TI  - Oral and intra-articular remedies: Review of papers published from March 2001 to
      February 2002.
AB  - There have been considerable advances in the drug treatments used to treat
      osteoarthritis. The development of selective cyclo-oxygenase inhibitors (COX-II)
      and confirmation of their efficacy and gastrointestinal safety will reduce
      treatment morbidity in the elderly. Guidelines for safe and appropriate use of
      COX-II drugs are now available. The role of anti-inflammatory drugs in
      precipitating cardiorenal events has been highlighted but remains to be fully
      evaluated. Glucosamine, diacerein, and hyaluronan may all be disease-modifying
      drugs for osteoarthritis but confirmatory studies are still needed.

PMID- 12192263
TI  - Nonpharmacologic management of osteoarthritis.
AB  - Several nonpharmacologic interventions for osteoarthritis are in different stages
      of development, investigation, and application. Such interventions capitalize on
      current knowledge of the causes of symptoms, disease progression, and disability
      in patients with osteoarthritis. Many nonpharmacologic interventions are low in
      cost and incorporate self-management approaches or home-based activities and, as
      such, may ultimately have substantial public health impact. Recent studies and
      reviews of exercise, weight loss, education, inserts, footwear, bracing,
      therapeutic ultrasound, acupuncture, and pulsed electromagnetic field therapy
      will be highlighted in this review. For many of these interventions, further
      investigation will be necessary to define their place in the management of
      osteoarthritis.

PMID- 12192264
TI  - Lymphoma therapy: the challenges ahead.

PMID- 12192265
TI  - Reduced-intensity allogeneic transplantation for lymphoma.
AB  - Reduced-intensity allogeneic transplants are promising, increasingly used
      treatments for hematologic malignancies, exploiting graft-versus-tumor effects
      for eradicating malignancies. This article reviews approximately 40 published
      reports of reduced-intensity allogeneic transplants in lymphomas. Overall,
      reduced-intensity allogeneic transplants have been well tolerated and have
      produced encouraging results despite a diversity of transplant approaches used
      largely in heavily pretreated and older patients. Of 368 lymphoma patients who
      underwent reduced-intensity allogeneic transplants, 66.3% had responses, most of
      which were complete. Many had chemotherapy-refractory lymphomas, including some
      that relapsed after autologous transplants. Although the short follow-up periods
      of many studies do not permit assessments of response duration, protracted
      remissions were reported in some studies. Additionally, some patients entered
      molecular remissions, suggesting that graft-versus-tumor effects could, by
      themselves, cure some lymphomas. Graft-versus-host disease is the major risk of
      reduced-intensity allogeneic transplants, and treatment methods need refinement
      to reduce transplant risks while preserving graft-versus-tumor effects.
      Controlled trials involving patients with earlier-stage disease appear warranted
      to define better the role of reduced-intensity allogeneic transplants in treating
      lymphomas.

PMID- 12192266
TI  - Radioimmunotherapy in non-Hodgkin lymphoma.
AB  - Targeted therapy using monoclonal antibodies against a tumor-specific antigen is
      now an established mode of therapy in the management of malignant lymphomas.
      Radioimmunotherapy, a novel way of delivering systemic radiotherapy concurrently
      with immunotherapy, has finally appeared on the horizon, with promising results.
      Recent clinical trials have demonstrated the safety and efficacy of
      radioimmunoconjugates. Durable antitumor responses have been achieved, even in
      heavily pretreated patients. The optimal position that these novel agents should
      take in the algorithm of lymphoma therapy remains to be defined.

PMID- 12192267
TI  - Potential methods to circumvent blocks in apoptosis in lymphomas.
AB  - We review our current understanding of the molecular determinants and mechanisms
      of lymphocyte apoptosis and identify the key regulators of these death-signaling
      pathways. In addition, we describe the key molecular aberrations that underlie
      the resistance of lymphomas to conventional therapy, and highlight the enormous
      promise of potential therapeutic strategies that could circumvent or overcome
      these genetic impediments to apoptosis.

PMID- 12192269
TI  - Present standards for cervical cancer screening.
AB  - Survival rates for cancer of the uterine cervix have improved over the last 40
      years largely because of the impact of screening measures such as the Pap smear.
      The ability to screen and treat women for preinvasive disease, cervical
      dysplasia, is the key factor leading to the reduction in the incidence of
      invasive cervical cancer. More recently, the ability to test women for the
      causative agent, the human papilloma virus, has emerged as a potential screening
      tool. New research has focused on new technologies for Pap smear screening such
      as thin layer technology, the appropriate intervals for screening, and the
      appropriate methods of incorporation of human papilloma virus testing into the
      screening protocols. Reviews of published studies evaluating the efficacy of new
      technologies suggest that there is still insufficient information to confirm
      improved outcome; however, results to date suggest that thin layer Pap smear
      technology may improve sensitivity in the detection of cervical dysplasia.
      Automated rescreening technologies in use may decrease the number of false
      negative Pap smears and are an option for laboratories. Various professional
      groups and countries have differing recommendations on the interval for
      screening, primarily on the basis of cost-effectiveness. Some of the most
      important new information this year regarding cervical cancer screening includes
      the new Bethesda System for the reporting of Pap smears and the new guidelines
      for the management of the abnormal Pap smear by the American Society of
      Colposcopy and Cervical Pathology. These guidelines incorporate human papilloma
      virus testing based on a multicenter trial documenting its efficacy in the triage
      of women with atypical squamous cells on Pap smear. These recommendations are
      reviewed along with the current literature on cervical cancer screening.

PMID- 12192270
TI  - Surgical chores and approach in the management of endometrial cancer.
AB  - Carcinoma of the uterine corpus is the most common malignancy in the female
      pelvis. Surgical resection and staging are now the accepted approach to therapy,
      with excellent survival compared with other gynecologic malignancies. Several
      controversies exist, however, regarding optimal surgical management. Some of
      these controversies are addressed in this article, with a review of their recent
      and historic literature.

PMID- 12192271
TI  - Management of recurrent ovarian cancer: evidence-based decisions.
AB  - In this era of advanced medical technology, recurrent ovarian cancer continues to
      be a therapeutic dilemma. Most of these patients will succumb to their disease
      process. For this reason, it is of paramount importance for all clinicians to
      recognize that the primary goal of salvage therapy is to maximize disease-free
      survival and quality of life. With this goal in mind, they can offer patients a
      variety of different modalities to control disease, including second-look
      surgery, secondary or interval cytoreduction, second-line chemotherapy, hormonal
      therapy, and immunotherapy. The role of second-look surgery has yet to be
      delineated, but the modality can be helpful in evaluating disease status and
      guiding further therapy in patients receiving first-line platinum-based
      chemotherapy or in research protocols. Interval cytoreductive surgery has been
      shown to confer a survival advantage in a small subset of patients with localized
      resectable disease proven to be platinum sensitive. The choice of
      chemotherapeutic agents and the prognosis depend directly on whether the patient
      is a platinum-sensitive responder. Many agents are approved for the treatment of
      recurrent ovarian cancer, and the treatment of each patient should be
      individualized depending on the cumulative toxicities and performance status.
      Extensive ongoing research trials are underway to elucidate the best salvage
      therapy.

PMID- 12192272
TI  - B-cell activation and lymphoma in patients with HIV.
AB  - The risk of developing non-Hodgkin lymphoma (AIDS lymphoma) is greatly increased
      in HIV infection. Disruption of immune function by HIV infection may contribute
      to lymphomagenesis by inducing (1) loss of immunoregulation of Epstein-Barr virus
      infected B cells [immunoblastic and central nervous system (CNS) lymphoma] caused
      by loss of T-cell function, and (2) chronic B-cell hyperactivation enhancing the
      generation of genetic lesions (c- :immunoglobulin gene translocation, -6
      overexpression) associated with some forms of AIDS lymphoma (Burkitt lymphoma
      like small noncleaved cell lymphoma and large noncleaved cell lymphoma). Also,
      the overproduction of B-cell-stimulatory cytokines (interleukin 10 and 6) has the
      potential to contribute to tumor development by supporting the growth and
      viability of nascent lymphoma cell clones. Therefore, HIV infection-associated B
      cell hyperactivation, including direct activation of B cells by various
      mechanisms, and chronic overproduction of B-cell-stimulatory cytokines have the
      potential to contribute to the development and growth of AIDS lymphoma. Several
      recent reports are discussed in this review, including recent work relevant to
      understanding the potential of a virus-encoded cytokine-like molecule, HHV8 vIL6,
      to induce B-cell hyperactivation in HIV-infected people, work pointing to the
      potential role of a chemokine (stromal cell-derived factor 1) in lymphomagenesis,
      and studies on phenotypic changes in circulating B cells in HIV infection.

PMID- 12192274
TI  - Hepatitis viruses and hepatocellular carcinoma in HIV-infected patients.
AB  - Hepatocellular carcinoma, the most common primary cancer of the liver, results in
      significant morbidity and mortality. Several disease entities have been shown to
      predispose to hepatocellular carcinoma. In most cases, however, hepatitis B
      virus, hepatitis C virus, and cirrhosis are the principal etiologic factors. In
      HIV-positive patients, a significant increase in the incidence of certain
      malignancies has been noted. Although HIV and the hepatitis viruses share common
      modes of transmission, an increase in the incidence of hepatocellular carcinoma
      in the patients with HIV has not been observed. This finding may be a function of
      premature death in patients with HIV before the advent of effective
      antiretroviral therapy. The introduction of such therapy may alter the
      epidemiology of hepatocellular carcinoma and strain health services, because
      current treatment options targeting both the underlying causative viruses and
      liver cancer itself are unsatisfactory and are the subject of ongoing research.

PMID- 12192275
TI  - Plasma cell dyscrasia, Hodgkin lymphoma, HIV, and Kaposi sarcoma-associated
      herpesvirus.
AB  - Plasma cell dyscrasias appear to have a modestly increased incidence in patients
      with HIV and AIDS as determined by registry linkage studies. As with Hodgkin
      lymphoma in HIV patients, the presentation is often unusual and aggressive, and
      these tumors are commonly associated with Epstein-Barr virus. Little evidence
      suggests a link with Kaposi sarcoma-associated herpesvirus.

PMID- 12192273
TI  - Epstein-Barr virus DNA in body fluids.
AB  - Advances in polymerase chain reaction technology have greatly simplified the
      ability to detect and monitor Epstein-Barr virus DNA copy number in a variety of
      settings. An initial focus on cell-associated viruses by many investigators has
      shown some interesting results regarding the dynamics of Epstein-Barr virus
      infection. Several findings are unexpected. A relation between HIV load or CD4 T
      cell counts and Epstein-Barr virus copy number is not seen. Furthermore, highly
      active antiretroviral treatment therapy in HIV patients that results in a rise of
      CD4 T cells may sometimes be associated with a rise in cell-associated Epstein
      Barr virus load. Detection of Epstein-Barr virus in spinal fluid is useful in the
      diagnosis of primary central nervous system lymphoma, and monitoring of Epstein
      Barr virus DNA copy number in spinal fluid may be useful in assessing response.
      Cell-free DNA in serum or plasma is emerging as a useful diagnostic tool in
      several settings. Fetal DNA can be detected in maternal serum or plasma. Tumor
      DNA can be detected in serum or plasma in association with a variety of cancers.
      Epstein-Barr virus DNA in serum or plasma has been found in infectious
      mononucleosis, nasopharyngeal carcinoma, posttransplant lymphoma, and nasal
      lymphoma. In each of these malignancies, its detection or quantification has been
      shown to be of prognostic significance. The utility of Epstein-Barr virus DNA
      detection and quantification in the serum or plasma of patients with HIV
      malignancies has yet to be determined but holds great promise.

PMID- 12192276
TI  - Complex regional pain syndrome after thromboendarterectomy: which type is it?
AB  - The authors describe a complex regional pain syndrome (CRPS) and discuss its type
      according to the presence or absence of nerve injury. A patient underwent
      thromboendarterectomy of the right popliteal artery. Subsequently, right lower
      limb reflex sympathetic dystrophy developed, which was confirmed by scintigraphy
      and responded well to calcitonin treatment. Typing according to the new
      classification of CRPS type I or II with possible nerve injury is discussed, and
      a short review of the literature is included.

PMID- 12192277
TI  - Utility of planar bone scintigraphy to distinguish benign osteochondromas from
      malignant chondrosarcomas.
AB  - PURPOSE: The current study was designed to evaluate the role of planar bone
      scintigraphy in the diagnosis of sarcomatous change in osteochondromas
      (cartilaginous exostoses). MATERIALS AND METHODS: Histologically verified cases
      of chondrosarcoma and osteochondroma, in which Tc-99m bone scintigraphy was
      performed, were reviewed in a retrospective study. RESULTS: Twenty-two cases were
      evaluated. Of 11 cases with chondrosarcomas, 8 (73%) had clearly increased tracer
      uptake, whereas the remaining cases had normal or decreased tracer uptake. Of the
      11 cases with osteochondromas, 8 (73%) had clearly increased tracer uptake,
      whereas the remaining cases had normal or decreased tracer uptake. No significant
      difference in the distribution of scintigraphic results was noted between the two
      pathoanatomic groups (p = 1). CONCLUSION: In conclusion, single standing planar
      bone scintigraphy has no value in distinguishing benign osteochondromas from
      malignant chondrosarcomas.

PMID- 12192278
TI  - Scintigraphy of injuries to the distal tibiofibular syndesmosis.
AB  - Ankle sprains are a common injury and may occur in as many as 75% of sporting
      participants. More complex injuries involving a rotational component may lead to
      injury of the interosseous membrane, its supporting ligaments, or the tibial
      plafond, compromising the integrity of the ankle mortice. Four such cases that
      show the scintigraphic manifestation of the injury are presented. In addition to
      the standard planar views of the ankles, special magnified anterior views were
      obtained with the feet in internal rotation of 25 degrees to 35 degrees. These
      special views facilitated the diagnoses.

PMID- 12192279
TI  - Incidental detection of colon cancer by FDG positron emission tomography in
      patients examined for pulmonary nodules.
AB  - PURPOSE: Fluorodeoxyglucose (FDG) positron emission tomographic (PET) imaging has
      been used extensively to diagnose cancer with high rates of sensitivity and
      specificity. One of its applications is to distinguish benign from malignant
      pulmonary nodules. It is common to observe colonic uptake on whole-body FDG-PET
      images. Because patients with lung cancer also tend to be in the age group with
      the highest incidence of colon cancer, the authors tried to assess the efficacy
      of FDG-PET for detecting occult colon cancer in patients referred for the
      evaluation of lung nodules. METHODS: The records of 500 consecutive patients
      referred for the evaluation of pulmonary nodules were reviewed retrospectively.
      Among the patients, 197 had no previous clinical or radiographic evidence of
      abnormalities in the gastrointestinal tract, and none had been found to have any
      cancer before undergoing an FDG-PET study. All colon lesions were verified either
      by histologic analysis or by clinical course. RESULTS: Among the 197 patients
      analyzed, 59 had diffuse colonic uptake in various segments of the colon.
      Seventeen of the patients had focal colonic uptake, five of which were proved to
      be colon cancer. CONCLUSIONS: The routine use of FDG PET to characterize lung
      lesions significantly increases the probability of detecting unexpected
      extrathoracic disease. In these patients, the incidental finding of colon cancer
      had an important effect on their treatment and may prove to be very cost
      effective.

PMID- 12192280
TI  - Preliminary results of Tc-99m ECD SPECT to evaluate cerebral collateral
      circulation during balloon test occlusion.
AB  - PURPOSE: The authors obtained noninvasive quantitative measurements of regional
      cerebral blood flow using Tc-99m L,L-ethyl cysteinate dimer (Tc-99m ECD) SPECT to
      evaluate cerebral collateral circulation during balloon test occlusion (BTO) of
      the internal carotid artery and vertebral artery (VA). METHODS: Five cases
      associated with an aneurysm and a brain tumor were investigated. After 10 minutes
      of BTO, a bolus of Tc-99m ECD was injected intravenously and radionuclide
      angiography was performed. The balloon remained inflated for an additional 5
      minutes. After radionuclide angiography was completed, brain SPECT imaging was
      performed. For quantitative analysis, regions of interest were defined on the
      transverse images on each side of the anterior cerebral artery and middle
      cerebral artery territories in cases of occlusion of the internal carotid artery.
      Regions of interest were defined for the posterior cerebral artery territory and
      cerebellum in cases of occlusion of the VA. The percentage activity change during
      BTO was calculated. RESULTS: In two of the three patients in whom BTO of the
      internal carotid artery was performed, the percentage activity reduction of more
      than 30% was noted in the anterior cerebral and middle cerebral artery
      territories. These two patients underwent bypass grafting before carotid
      occlusion. In one of the two patients in whom BTO of the VA was performed, the
      percentage activity reduction of 16% was noted in the posterior cerebral artery
      territory. This patient underwent bypass grafting before occlusion of the VA.
      CONCLUSION: This noninvasive and quantitative method of cerebral blood flow
      measurement using Tc-99m ECD during BTO appears to have the potential to help
      select patients who may tolerate temporary or permanent arterial occlusion.

PMID- 12192281
TI  - Recurrent lymphoma detected on F-18 FDG coincidence imaging with negative
      findings on Ga-67 citrate scintigraphy.
AB  - Ga-67 citrate scintigraphy and computer tomography have been used in tumor
      staging, to determine disease extent, and for the pre- and post-therapeutic
      management of Hodgkin's and non-Hodgkin's lymphoma. Today, localization of
      hypermetabolic tissue using F-18 FDG is beginning to play a role in the staging
      and restaging of lymphoma. The authors report a case of recurrent Hodgkin's
      lymphoma in a 31-year-old man detected by F-18 FDG. Findings of the Ga-67 citrate
      scintigram were negative. Palpable right axillary adenopathy was found on routine
      physical examination follow-up. Comparison with previous negative findings
      obtained with Ga-67 citrate was unchanged. However, computed tomography revealed
      new right axilla lymphadenopathy, prompting further investigation with F-18 FDG
      SPECT, which showed hypermetabolic activity corresponding to the region of the
      right axilla involvement. Pathologic examination showed changes indicative of
      interfollicular recurrence of Hodgkin's lymphoma.

PMID- 12192282
TI  - Scintigraphic assessment of patients with electrocardiographic left ventricular
      hypertrophy with ST-T changes without apparent cause.
AB  - PURPOSE: Some patients who show electrocardiographic left ventricular hypertrophy
      with ST-T changes (ECG-LVH) are difficult to evaluate using routine examinations.
      To clarify the pathologic process in these patients, the authors performed
      several scintigraphic examinations. MATERIALS AND METHODS: Twenty-nine patients
      with ECG-LVH, without apparent cause, such as left ventricular (LV) systolic
      overloading or increased LV mass, were examined by myocardial I-123 MIBG imaging,
      I-123 BMIPP imaging, and exercise-induced stress perfusion imaging. In addition
      to the visual assessment of each image, we calculated global and regional
      myocardial washout of I-123 MIBG (%washout). The LV was assessed using
      conventional echocardiography. RESULTS: Visually observed abnormalities were
      located exclusively at the LV apex with all imaging methods and were detected in
      76%, 52%, and 17% of patients by I-123 MIBG, I-123 BMIPP, and perfusion imaging,
      respectively. A follow-up study revealed that the apical defects of I-123 MIBG
      were subsequently followed by defects of I-123 BMIPP and then perfusion
      abnormalities. In patients with an apical defect revealed by I-123 MIBG imaging,
      apical %washout was high. In nine patients who underwent myocardial biopsy,
      myocardial disarray was observed at the apical regions. CONCLUSIONS: In many
      patients with ECG-LVH without apparent cause, sympathetic abnormalities are
      observed at the apex, similar to pathologic changes in hypertrophic
      cardiomyopathy. These abnormalities may lead to changes in fatty acid metabolism
      and perfusion.

PMID- 12192283
TI  - Timing of sentinel lymphadenectomy in cutaneous melanoma.
AB  - PURPOSE: The conduct of sentinel lymphadenectomy for cutaneous melanoma varies
      substantially among the medical disciplines. The authors sought to characterize
      the number of hot spots identified during preoperative lymphoscintigraphy for
      cutaneous melanoma and to determine its relation to the harvesting of sentinel
      lymph nodes. METHODS: Sixty-nine patients with cutaneous melanoma underwent
      lymphoscintigraphy with filtered Tc-99m sulfur colloid before sentinel
      lymphadenectomy. The lymphoscintigrams were reviewed and the number of hot spots
      visualized over time and the number of sentinel nodes harvested were determined.
      RESULTS: Lymphoscintigraphy identified 79 patients with 87 lymphatic basins at
      risk for metastatic disease. Lymphoscintigraphy was performed in a mean time of
      30 minutes (range, 15 to 40 minutes). The mean number of hot spots increased from
      0.2 to 2.0 hot spots 40 minutes after the initial static image, but the number of
      hot spots stabilized between 20 and 40 minutes. The same number of sentinel nodes
      as hot spots visualized were harvested in 58% of patients. Fewer sentinel nodes
      were identified at the time of surgery than were visualized by lymphoscintigrams
      in 39% of patients. CONCLUSIONS: More hot spots were identified up to 40 minutes
      after the initiation of lymphoscintigraphy. Sentinel lymphadenectomy can be
      performed as near to 40 minutes after the initiation of lymphoscintigraphy as is
      logistically reasonable. However, there may be substantial latitude in delayed
      performance of sentinel lymphadenectomy.

PMID- 12192284
TI  - Tc-99m MDP uptake secondary to soft tissue extravasation of calcium gluconate in
      a newborn thought to have osteomyelitis.

PMID- 12192285
TI  - Thyroid nodule mimicking cervical adenopathy on FDG positron emission tomographic
      imaging.

PMID- 12192286
TI  - Incidental thyroid carcinoma on parathyroid imaging.

PMID- 12192287
TI  - Enhanced filling and cholecystokinin-induced emptying of the human gallbladder
      after glyceryl trinitrate administration: a scintigraphic sign of functional
      cystic duct syndrome.

PMID- 12192288
TI  - Intense accumulation of Ga-67 citrate in solid and cystic tumors of the pancreas.

PMID- 12192289
TI  - Tc-99m MDP and Ga-67 citrate images in suppurative costochondritis.

PMID- 12192290
TI  - Demonstration of ventriculoperitoneal shunt infection on Ga-67 citrate
      scintigraphy.

PMID- 12192291
TI  - Localization of gastrointestinal bleeding using Tc-99m HSA-DTPA SPECT and maximum
      intensity projection imaging.

PMID- 12192293
TI  - Tracheal granuloma after tracheal intubation incidentally detected on Ga-67
      imaging.

PMID- 12192292
TI  - Diffuse soft tissue uptake on a bone scan in a patient receiving alpha-interferon
      therapy.

PMID- 12192294
TI  - Excessive colon activity from antidiarrheal medication causing false-positive In
      111 octreotide studies.

PMID- 12192295
TI  - Comparative SPECT findings of Tc-99m depreotide, Tc-99m tetrofosmin, and Tl-201
      chloride for bronchogenic carcinoma.

PMID- 12192296
TI  - F-18 FDG positron emission tomographic imaging in bilateral iliopsoas abscesses.

PMID- 12192297
TI  - Effect of hyperglycemia on tumoral uptake of F-18 FDG.

PMID- 12192298
TI  - Additional evidence that the sympathetic nervous system regulates the vessel wall
      release of tissue plasminogen activator.
AB  - It is established that sympathetic neurons can synthesize, transport and store
      tissue plasminogen activator (t-PA) within axon terminals in the smooth muscle of
      vessel walls. Moreover, sympathetic excitations (e.g. physical and mental stress)
      are known to induce an acute release of t-PA into the circulation. However,
      relatively little is known about the nature and extent of sympathetic nervous
      system involvement in the release process. We inquired whether a chemical
      sympathectomy will alter the release of t-PA into the blood, and the intrinsic
      release of stored t-PA from isolated whole vessel explants. A long-term
      sympathectomy was induced in adult Sprague-Dawley rats by injection of
      guanethidine during a 5-week course. The destruction of ganglion neurons and
      vessel wall axons was verified immunohistochemically. t-PA release was assayed as
      the free activity in hind limb plasma and explant culture medium. Following
      sympathectomy: (i) the basal t-PA activity in plasma was 70% less than controls
      (2.92 +/- 1.96 versus 9.33 +/- 1.72 IU/ml; </= 0.001); (ii) the acute release
      from isolated vessels induced by bradykinin or phenylephrine was comparably
      reduced; and (iii) the greatest reductions occurred in densely innervated small
      vessel explants. The results provide new support for an autonomic regulation of
      neural t-PA release into the vessel wall matrix and blood of densely innervated
      thin-walled microvessels.

PMID- 12192299
TI  - The K469E polymorphism of the ICAM-1 gene is a risk factor for peripheral
      arterial occlusive disease.
AB  - Intercellular adhesion molecule-1 (ICAM-1) plays a crucial role in lymphocyte
      migration and activation, and is considered important in the pathogenesis of
      atherosclerosis. K469E is a common polymorphism of the ICAM-1 gene with potential
      functional significance. The aim of the present case-control study was to
      evaluate the association between this polymorphism and peripheral arterial
      occlusive disease (PAOD). ICAM-1 gene polymorphism was examined by polymerase
      chain reaction and restriction enzyme analysis in 75 Italian subjects affected by
      PAOD and 227 controls. The distribution of ICAM-1 genotypes in patients affected
      by PAOD was 32.1% EE, 50.6% EK, and 17.3% KK. The distribution of ICAM-1
      genotypes in control subjects was 17.2% EE, 55.1% EK, and 27.7% KK. The EE
      genotype was significantly more common in patients than controls (P = 0.006).
      Logistic regression analysis indicated that the presence of the EE genotype
      significantly increases the risk of PAOD (odds ratio, 3.5; 95% confidence
      interval, 1.5-8.4; P = 0.004). This is the first study documenting a role of the
      ICAM-1 gene polymorphism in the pathogenesis of a cardiovascular disease, such as
      PAOD. Our data support the hypothesis that inflammatory mechanisms are important
      in the pathophysiology of vascular diseases with an atherosclerotic basis.

PMID- 12192300
TI  - Activation of factor IX by erythrocyte membranes causes intrinsic coagulation.
AB  - As an extension of our earlier work, procoagulant activity of erythrocyte [red
      blood cell (RBC)] membrane was examined using biochemical and rheological
      techniques. Western blot analysis of coagulation factors incubated with
      erythrocytes (RBCs) showed that only factor IX (FIX) was activated by RBC
      membranes in the presence of calcium ions. A fluorogenic assay suggested that
      activated FIX is capable of activating factor X. A preliminary crude extraction
      of the substance from RBC membranes suggested that a FIX-activating enzyme may be
      located on the RBC membrane. The initiation of FIX activation by RBCs was
      enhanced by an elevation in hematocrit. Moreover, the rate of FIX activation by
      RBCs from normal pregnant women and diabetic patients was much faster than that
      from normal subjects. In addition, glucose treatment of normal RBCs resulted in
      the increase in procoagulant activity. It is suggested that FIX activation by RBC
      membranes may serve as a triggering mechanism for blood coagulation, although
      further study will be required to clarify the putative FIX activating enzyme on
      the RBC membrane and to permit more extensive physiological experiments to be
      performed.

PMID- 12192301
TI  - A new model to evaluate the diet-induced prothrombotic state, using He-Ne laser
      induced thrombogenesis in the carotid artery of apolipoprotein E-deficient and
      low-density lipoprotein receptor-deficient mice.
AB  - Epidemiological studies suggest the high fat content of the Western diet to be
      responsible for atherosclerosis and its thrombotic complications. Despite such a
      prevailing view, few animal experiments have so far succeeded in demonstrating
      enhanced thrombogenicity due to a high fat diet. Even a high fat and a very high
      cholesterol (1%) diet has failed to demonstrate an enhanced thrombotic reaction
      in rodents and rabbits. The aim of the present study was twofold. First, we
      wanted to establish a new, sensitive and specific thrombosis model in mice, which
      can then be used to study the effect of diets. Second, we intended to employ such
      a thrombosis model in investigations into the effect of high or low fat diets on
      thrombosis. The technique described uses a laser to induce thrombus formation in
      the exposed carotid artery of apolipoprotein E-deficient and low-density
      lipoprotein receptor-deficient mice. Thrombus formation was recorded on video,
      analysed by computer, and the size of thrombus was calculated by image analysis
      software. Thrombotic status was evaluated by analysing a total of 61 individual
      images of the thrombotic reaction, which were taken over 600 s. The severity of
      atherosclerosis was assessed by image analysis of the stained elastic fibers. Two
      kinds of diets were used: the Western type, high fat diet contained 20% fat (w/w)
      and 0.05% cholesterol (w/w); the low fat diet contained 7% fat, without
      cholesterol. These diets were on the basis of AIN93G and were given to mice for 4
      or 8 weeks. The high fat diet significantly enhanced both the thrombotic reaction
      and the development of atherosclerosis as compared with the low fat diet.

PMID- 12192302
TI  - Platelet-CD40 ligand interaction with melanoma cell and monocyte CD40 enhances
      cellular procoagulant activity.
AB  - Platelet-tumor cell interactions are believed to be important in tumor
      metastasis. Tumor cell tissue factor (TF) expression enhances metastasis and
      angiogenesis, and is primarily responsible for tumor-induced thrombin generation
      and the formation of tumor cell-platelet aggregates. Activated platelets express
      and release CD40 ligand (CD40L), which induces endothelial TF expression by
      ligation to CD40. We investigated the effect of platelet-derived CD40L on the TF
      activity of human CD40-positive melanoma cells and monocytes by incubating
      supernatants from activated or resting platelets with tumor cells or monocytes,
      and by bringing resting or activated platelets into close apposition with tumor
      cell monolayers. CD40L was present on the surface of activated (but not resting)
      platelets and was also released following platelet activation. Both recombinant
      soluble CD40L (rsCD40L) and activated platelet supernatants increased
      procoagulant activity (PCA) and TF antigen in tumor cells and monocytes. The
      increase in TF activity induced by both rsCD40L and activated platelet
      supernatants was inhibited by anti-CD40L antibody. Furthermore, contact of
      activated platelets with tumor cells increased cellular PCA, and this effect was
      also inhibited by anti-CD40L. In malignancy, the increase in cellular TF activity
      via CD40 (tumor cell)-CD40L (platelet) interaction may possibly enhance
      intravascular coagulation and hematogenous metastasis.

PMID- 12192303
TI  - Relationship between plasma markers of endothelial cell integrity and the
      Framingham cardiovascular disease risk-factor scores in apparently healthy
      individuals.
AB  - Separate reports have identified differences in plasma levels of the endothelial
      markers soluble E-selectin, von Willebrand factor (vWf) and soluble
      thrombomodulin in each of the major modifiable risk factors for atherosclerosis
      (smoking, hypertension and hypercholesterolaemia), and abnormal levels of some
      plasma markers predict various adverse cardiovascular events. However, it is
      unclear whether there is an increasing effect on the endothelium with a worsening
      risk-factor profile. We measured the three endothelial cell markers by enzyme
      linked immunosorbent assay in the plasma of 200 subjects (mean age, 54 years; 58%
      men) free of the symptoms and clinical signs of atherosclerosis. Levels of the
      markers were then correlated with the Framingham coronary heart disease (CHD) and
      cerebrovascular disease (CVD) scores to help determine which (if any) may be
      useful as good laboratory predictors of future cardiovascular events in
      prospective epidemiological studies. vWf correlated with CHD (r(s) = 0.269, <
      0.001) and CVD risk (r(s) = 0.331, P < 0.001), but soluble E-selectin correlated
      only with CHD risk (r(s) = 0.163, P = 0.021). We conclude that, of the three
      specific endothelial markers, vWf correlates most closely with the Framingham
      risk-factor prediction scores and therefore may be the better plasma endothelial
      marker of the future development of an atherothrombotic event.

PMID- 12192304
TI  - Characterization of the human prostaglandin H synthase 1 gene (PTGS1): exclusion
      by genetic linkage analysis as a second modifier gene in familial thrombosis.
AB  - Genetic evidence from a large Vermont kindred indicates that an unknown gene
      promotes thrombosis when inherited in conjunction with type I protein C
      deficiency. Cyclooxygenase-1 [prostaglandin H synthase 1 gene (PTGS1)] was tested
      as a plausible candidate for the unknown gene because of its role in primary
      hemostasis. The complete sequence of PTGS1 (25 638 nucleotides) was determined
      from a 37 kb human genomic cosmid clone to characterize intronic regions and
      subsequently to allow the search for mutations by direct sequencing of genomic
      DNA. Northern blot analysis confirms usage of a newly described distal poly
      adenylation signal. Short tandem repeat (STR) sequences found in intron 2 and the
      3' flanking region were developed as new genetic markers for PTGS1. The position
      of PTGS1 was refined on the CHLC chromosome 9 linkage map using the new markers
      scored in four Centre d'Etude du Polymorphisme Humain families and multipoint
      linkage analysis. Direct sequencing of DNA from members of the Vermont kindred
      led to the discovery of two new single nucleotide polymorphisms (SNPs) that give
      rise to non-conservative amino acid changes in the signal peptide (Arg(8) to Trp
      and Pro(17) to Leu) of cyclooxygenase-1. Linkage analysis of the SNP and STR
      markers indicated that PTGS1 is not the interacting gene associated with an
      increased incidence of thrombosis in the Vermont kindred.

PMID- 12192305
TI  - Analyzing fibrin clot structure using a microplate reader.
AB  - Fibrin clot structure studies are often performed using optical methods. For
      example, the clot's fiber structure can be assessed by measuring light scattering
      as a function of wavelength. From these measurements, one can calculate the
      mass/length ratio (mu), a relative measure of fibrin thickness. Fiber thickness
      has important functional correlates in terms of clot stability and resistance to
      fibrinolysis. Typically, measurements to calculate mass/length ratios are carried
      out on high-end spectrophotometers. However, limitations of this instrument
      include the large sample volume required and the inability to read multiple
      samples at one time. To circumvent these limitations, a plate-reading
      spectrophotometer is more commonly used to monitor clot formation; increases in
      absorbance indicate clot formation, while decreases indicate clot lysis. However,
      it is unclear whether plate-reading spectrophotometers can be used to
      quantitatively evaluate fibrin fiber structure. In the current study, we compared
      spectrophotometric analysis of fibrin gels on single-sample and plate-reading
      spectrophotometers. Results show that a plate-reading spectrophotometer does not
      give accurate measurements of the fiber mass/length ratio. However, the plate
      reading spectrophotometer can provide a qualitative measure of fiber structure
      for both purified fibrinogen and plasma. We suggest that plate-reading
      spectrophotometers can provide a convenient, rapid, and inexpensive means of
      analyzing fibrin clot structure.

PMID- 12192306
TI  - Regulation of plasminogen activator inhibitor-1 secretion by growth factors in
      smooth muscle cells.
AB  - Epithelioid-type vascular smooth muscle cells are metabolically active and
      secrete many proteases and protease inhibitors. We have previously cloned
      epithelioid-type smooth muscle cells from rat carotid arteries, and showed that
      polypeptide growth factors basic fibroblast growth factor (bFGF) and platelet
      derived growth factor (PDGF) could dose-dependently induce plasminogen activator
      inhibitor-1 (PAI-1) secretion from these cells. In the present study, we have
      used these cells to investigate the growth factor-induced signal transduction
      pathways leading to PAI-1 secretion. We report here that PAI-1 induction was
      dependent on protein kinase C (PKC) and tyrosine kinase but not on protein kinase
      A (PKA), ras and phosphoinositol-3-kinase inhibitor. Induction of PAI-1 by bFGF
      and PDGF was also accompanied by activation of a mitogen-activated protein kinase
      pathway involving Raf/Mek/Erk1/2, and the family non-receptor tyrosine kinases.,
      another non-receptor tyrosine kinase, on the contrary, behaved differently from
      in that it was part of a pathway leading to PAI-1 induction by bFGF, but not when
      PDGF was used as the stimulating reagent. Activation of a PKA-dependent
      pathway(s) opposed PAI-1 induction. One mechanism for PKA activators to inhibit
      PAI-1 secretion was that they markedly inhibited the phosphorylations of Mek and
      mitogen-activated protein kinase that were up-regulated in the presence of bFGF
      and PDGF.

PMID- 12192307
TI  - Successful thyroidectomy in a patient with Hermansky-Pudlak syndrome treated with
      recombinant activated factor VII and platelet concentrates.
AB  - Hermansky-Pudlak syndrome is a rare autosomal recessive disorder characterized by
      the absence of platelet dense bodies in association with albinism. We present the
      use of recombinant activated factor VII (rFVIIa) in a patient with Hermansky
      Pudlak syndrome who underwent total thyroidectomy because of a large richly
      vascularized nodule (10 cm) compressing the trachea. The patient had a prolonged
      bleeding time (> 20 min) that remained unchanged after platelet transfusions.
      However, after infusion of platelets plus rFVIIa, it diminished to 5 min. The
      platelet aggregation response to adenosine diphosphate and collagen was
      diminished. Since an early age, the patient had repeated nose bleeding and an
      episode of melena requiring several tampons, cauterization and transfusions of
      packed red cells. In this case, we used rFVIIa in bolus for 1 day (four doses of
      120 microg/kg every 2 h and six doses of 100 microg/kg every 3 h) and transfusion
      of platelet concentrates beginning just prior to surgery. No evidence of local
      bleeding complication could be detected during the entire post-operative period.
      The hemoglobin level remained normal and no transfusions of packed red cells were
      necessary. No adverse events occurred.

PMID- 12192308
TI  - Life-threatening bleeding and acquired factor V deficiency associated with
      primary systemic amyloidosis.
AB  - Acquired factor X deficiency has been described in patients with amyloidosis but
      acquired factor V deficiency is quite rare. We report here a case of life
      threatening bleeding and acquired factor V deficiency associated with primary
      amyloidosis. A 50-year-old man who had no previous hemorrhagic diathesis was
      referred to our hospital because of recurrent epistaxis, gingival bleeding and
      hemospermia. The laboratory examination revealed that both the prothrombin time
      (PT) and the activated partial thromboplastin time (aPTT) were significantly
      prolonged, and factor V activities were markedly decreased to 14-39% of the
      normal value. Other coagulation factors such as fibrinogen, prothrombin, factor
      VII, factor VIII, factor IX and factor X were subnormal and normal. Transaminases
      were slightly elevated but serological tests of hepatitis B and hepatitis C were
      negative. Mild hepatosplenomegaly was noted without sign of liver cirrhosis. The
      PT and aPTT obtained 8 years ago when he received a cholecystectomy due to
      cholecystitis were both normal. Specific assays for the detection of factor V
      inhibitor were repeatedly performed but no factor V inhibitor was found.
      Furthermore, a significant recovery of the infused factor V was noted shortly
      after an intravenous administration of 5-10 U fresh frozen plasma, but it did not
      last more than 6 h. Melena, bleedings into the left shoulder and buttock, and
      finally mortal retroperitoneal hemorrhage developed despite repeated infusions of
      large amounts of fresh frozen plasma. Acquired factor V deficiency associated
      with primary amyloidosis was suspected but histological diagnosis was not
      obtained because of the severe bleeding tendency. Autopsy revealed
      hepatosplenomegaly and massive deposits of AL amyloid in the liver, spleen, heart
      and other parenchymal organs. Perivascular amyloid deposition and factor V
      deficiency are both thought to be the cause of the severe hemorrhagic tendency
      seen in this patient.

PMID- 12192309
TI  - Changes in high molecular weight kininogen levels during and after
      cardiopulmonary bypass surgery measured using a chromogenic peptide substrate
      assay.
AB  - High molecular weight kininogen (HK) is a co-factor in the blood-contact
      activation system. A chromogenic peptide substrate assay for HK (HKcs) has been
      developed in which test plasmas are mixed with diluted HK-deficient plasma and
      incubated with a soluble contact system activator that activates prekallikrein
      and factor XII. Calcium chloride, a synthetic thrombin inhibitor and a
      chromogenic peptide substrate for activated factor X (FXa) are then added. The
      FXa generated cleaves the FXa substrate releasing p-nitroanaline, which is
      measured photometrically. Test plasma HK values were calculated from a standard
      curve generated using a pooled normal plasma. Acceptable intra-assay and inter
      assay precision values were obtained and levels of HK up to 200% were measurable.
      The assay measured HK in plasmas deficient in factor XII, prekallikrein and
      factor XI, was not affected by antiphospholipid antibodies and gave an acceptable
      correlation (r = 0.95) when normal plasmas and mixtures of HK-deficient and
      normal pooled plasma, calculated to give HK levels of 25 and 50%, were compared
      using HKcs and a HK one-stage clotting assay. The HKcs was used to measure HK
      levels in seven patients undergoing cardiopulmonary bypass (CPB). HK levels fell
      significantly during CPB (P = 0.0014) and were significantly higher (P = 0.016) 6
      days after CPB, suggesting that HK may be a positive acute-phase reacting
      protein.

PMID- 12192310
TI  - Prevalence of inherited thrombophilia in young thrombosis patients from the East
      Bohemian region.
AB  - Venous thromboembolism is a multifactorial disease that is defined by multiple
      interactions between genetic and environmental components. Inherited
      thrombophilia may result in a hypercoagulable state that causes an increased
      tendency to thrombosis. We assessed the prevalence of factor V Leiden, factor II
      20210A, antithrombin III, protein C and protein S deficiency, and the presence of
      antiphospholipid syndrome among 325 thrombosis patients from the East Bohemian
      region with a first episode of thrombosis under the age of 45 years. The average
      age of the first thrombotic event was 34 years (age range, 14-45 years). These
      data are not known yet from this part of the Czech Republic. Factor V Leiden was
      found in 40%, factor II 20210A in 6%, antithrombin III deficiency in 4%, protein
      C deficiency in 6%, and protein S deficiency in 11% in this cohort. Lupus
      anticoagulant was detected in 8% and anticardiolipin antibodies in 6%. Our
      results confirm the usefulness of thrombophilia work-up in patients with venous
      thrombosis before the age of 45 years in our region. The diagnosis of inherited
      thrombophilia is important for further management of these patients.

PMID- 12192311
TI  - Reliability of the thrombelastograph.

PMID- 12192312
TI  - Surgery: a noble profession in a changing world.

PMID- 12192313
TI  - Lung transplantation in children.
AB  - OBJECTIVE: To report the authors' experience with pediatric lung transplantation
      (LTX) to provide an overview of patients selected for this procedure and their
      outcomes. SUMMARY BACKGROUND DATA: Pediatric LTX differs from adults in many
      ways, including recipient size, indications, posttransplant care, and
      rehabilitation. METHODS: Two hundred seven isolated lung transplants on 190
      children under the age of 18 years were performed from 1990 to the present. This
      represents the single largest series of lung transplants in children in the
      world. Thirty-two patients were less than 1 year of age, 22 were 1 to 5 years of
      age, 32 were 5 to 10 years of age, and 121 were 10 to 18 years old. The groups by
      major diagnostic category were cystic fibrosis (n = 89), pulmonary vascular
      disease (n = 44), bronchiolitis obliterans (n = 21), pulmonary alveolar
      proteinosis (n = 12), pulmonary fibrosis (n = 15), and other (n = 26). The
      average age at the time of transplant was 9.5 +/- 5.9 years (range 36 days to 18
      years). RESULTS: Survival by Kaplan-Meier analysis was 77% at 1 year, 62% at 3
      years, and 55% at 5 years. There was no significant difference in survival
      according to primary diagnosis leading to LTX or age at LTX. There were 25 early
      (<60 days) and 61 late deaths. The most common cause of early deaths was graft
      failure (13/25, 52%). The most common causes of late death were bronchiolitis
      obliterans (35/61, 57%), infection (13/61, 21%), and posttransplant malignancies
      (11/61, 18%). No patient died of acute rejection. In those surviving greater than
      3 months (mean follow-up 3.5 years, range 3 months to 11 years), the overall rate
      of occurrence of bronchiolitis obliterans was 46% (80/175) and the overall
      incidence of posttransplant malignancies was 24/175 (14%). Major risk factors for
      the development of bronchiolitis obliterans were age older than 3 years, more
      than two episodes of acute rejection, and organ ischemic time longer than 180
      minutes. CONCLUSIONS: In children, LTX is a high-risk but viable treatment for
      end-stage pulmonary parenchymal and vascular disease. The major hurdle to
      overcome in long-term survival is bronchiolitis obliterans.

PMID- 12192314
TI  - Recent trends in National Institutes of Health funding of surgical research.
AB  - OBJECTIVE: To compare the amount of National Institutes of Health (NIH) funding
      provided to departments of surgery with that provided to other major clinical
      departments, to examine the relationship between peer-review activity and funding
      success, and to compare trends in participation in the peer-review process
      between surgeons and representatives from other clinical departments. SUMMARY
      BACKGROUND DATA: Surgical research has made enormous contributions to human
      health. This work is fundamentally dependent on fair and unbiased distribution of
      extramural research funds from the NIH. To date, no published report has examined
      the relative distribution of extramural support between departments of surgery
      and other major clinical departments. METHODS: Data regarding funding trends and
      peer-review activity were obtained from the NIH and compared between departments
      of surgery and four nonsurgical departments (medicine, psychiatry, pediatrics,
      neurology). Award data were examined during 1996 to 2001. Participation trends
      were examined during 1998 to 2000. RESULTS: Success rates of surgical proposals
      were significantly lower than nonsurgical proposals. Differentials in success
      rates were greatest for proposals assigned to the National Cancer Institute,
      although relative underfunding for surgical research spanned all major
      institutes. Awards for surgical grants averaged 5% to 27% less than nonsurgical
      grants). Surgeons exhibited 35% to 65% less peer-review activity relative to
      nonsurgeons when normalized to grant submission activity. Overall, surgeons
      participated on sections where they made up a relatively smaller proportion of
      total review members compared to nonsurgeons. CONCLUSIONS: Surgical grant
      proposals are less likely to be funded and carry significantly smaller awards
      compared to nonsurgical proposals. Relatively fewer surgeons participate in the
      review process, and those who do are more likely to be in the minority within
      study sections. Multiple strategies are needed to address these trends and level
      the playing field for surgical research.

PMID- 12192315
TI  - Evolving techniques for mitral valve reconstruction.
AB  - OBJECTIVE: To analyze the effectiveness of new techniques of mitral valve
      reconstruction (MVR) that have evolved over the last decade, such as aggressive
      anterior leaflet repair and minimally invasive surgery using an endoaortic
      balloon occluder. SUMMARY BACKGROUND DATA: MVR via conventional sternotomy has
      been an established treatment for mitral insufficiency for over 20 years,
      primarily for the treatment of patients with posterior leaflet prolapse. METHODS:
      Between June 1980 and June 2001, 1,195 consecutive patients had MVR with ring
      annuloplasty. Conventional sternotomy was used in 843 patients, minimally
      invasive surgery in 352 (since June 1996). Anterior leaflet repair was performed
      in 374 patients, with increasing use over the last 10 years. Follow-up was 100%
      complete (mean 4.6 years, range 0.5-20.5). RESULTS: Hospital mortality was 4.7%
      overall and 1.4% for isolated MVR (1.1% for minimally invasive surgery vs. 1.6%
      for conventional sternotomy; =.4). Multivariate analysis showed the factors
      predictive of increased operative risk to be age, NYHA functional class,
      concomitant procedures, and previous cardiac surgery. The 5-year results for
      freedom from cardiac death, reoperation, and valve-related complications among
      the 782 patients with degenerative etiology are, respectively, as follows ( >.05
      for all end points): for anterior leaflet repair, 93%, 94%, 90%; for no anterior
      leaflet repair, 91%, 92%, 91%; for minimally invasive surgery, 97%, 89%, 93%; and
      for conventional sternotomy, 93%, 94%, 90%. CONCLUSIONS: These findings indicate
      that late results of MVR after minimally invasive surgery and after anterior
      leaflet repair are equivalent to those achievable with conventional sternotomy
      and posterior leaflet repair. These options significantly expand the range of
      patients suitable for mitral valve repair surgery and give further evidence to
      support wider use of minimally invasive techniques.

PMID- 12192316
TI  - Long-term outcome of neoadjuvant therapy for locally advanced breast carcinoma:
      effective clinical downstaging allows breast preservation and predicts
      outstanding local control and survival.
AB  - OBJECTIVE: To review the long-term follow-up data from the authors' institutional
      experience of 62 patients with locally advanced breast cancer (LABC) treated with
      a uniform multimodality regimen. The authors determined the rate of breast
      preservation, the disease-free and overall survival, and the factors associated
      with locoregional and distant recurrent disease. SUMMARY BACKGROUND DATA: It
      remains a challenge to achieve local and distant control of LABC. Over the last
      decade, preoperative or neoadjuvant chemotherapy has emerged as the standard of
      care for these patients. Successful tumor downstaging has been associated with
      increased rates of breast-conserving therapy (BCT), but the overall effect on
      long-term survival remains to be seen. METHODS: This study examines a cohort of
      62 patients with LABC treated at the authors' institution from 1992 to 1998. The
      uniform treatment regimen consisted of neoadjuvant doxorubicin (Adriamycin),
      followed by operation (BCT if sufficient clinical downstaging), followed by non
      cross-resistant cyclophosphamide/methotrexate/5-fluorouracil, followed by
      radiation therapy. Treatment was both dose-intensive and time-intensive, with a
      total treatment time of 32 to 35 weeks. RESULTS: In this patient population, the
      median age was 44 years, with approximately two thirds white patients and one
      third African American. Eighty-two percent of patients were clinical stage III at
      presentation, 13 patients had T4d inflammatory cancers, and 3 patients were stage
      IV at diagnosis. Eighty-four percent of patients demonstrated a significant
      clinical response to doxorubicin. Twenty-eight patients had sufficient clinical
      downstaging to attempt BCT, and 22 (45%) of 49 noninflammatory patients underwent
      successful BCT. Pathologic complete response was seen in 15% of patients. Median
      follow-up for the cohort was 70 months. The local recurrence rate was 14%,
      including two ipsilateral breast tumor recurrences (10%) in the BCT patients.
      Seven (12%) patients developed a new primary cancer in the contralateral breast.
      Distant metastases occurred in 18 (31%) patients, and the 5-year overall survival
      rate for the cohort was 76%. Furthermore, in the patients who underwent an
      attempt at BCT, the survival rate was 96% at 5 years. CONCLUSIONS: Dose-intensive
      and time-intensive multimodality neoadjuvant therapy was successfully
      administered to a mixed racial group over shortened times. Patients who had
      sufficient clinical downstaging to allow BCT have the best long-term outcome.
      Patients who required mastectomy are at a higher risk of relapse, as well as the
      development of new contralateral cancers, yet have 5-year survival rates of over
      50%.

PMID- 12192317
TI  - Repair of pectus excavatum and carinatum deformities in 116 adults.
AB  - OBJECTIVE: To determine the feasibility of surgically correcting pectus excavatum
      and carinatum deformities in adult patients. SUMMARY BACKGROUND DATA: Although
      pectus chest deformities are common, many patients progress to adulthood without
      surgical repair and experience increasing symptoms. There are sparse published
      data regarding repair of pectus deformities in adults. METHODS: Since 1987, 116
      patients over the age of 18 years with pectus excavatum (n = 104) or carinatum (n
      = 12) deformities underwent correction using a highly modified Ravitch repair,
      with a temporary internal support bar. The ages ranged from 19 to 53 years (mean
      30.1). Eighty-six patients sought repair after reviewing information regarding
      pectus deformities available on the Internet. Each patient experienced dyspnea
      with mild exertion and decreased endurance; 84 had chest pain with activity; 75
      had palpitations and/or tachycardia. Seven patients underwent repair for
      symptomatic recurrent deformities. The mean severity score (chest width divided
      by distance from sternum to spine) was 4.8. The sternal bar was removed from 101
      patients 6 months after the repair without complications. RESULTS: Each of the
      patients with reduced endurance or dyspnea with mild exercise experienced marked
      improvement within 6 months. Chest discomfort was reduced in 82 of the 84
      patients. Complications included pleural effusion (n = 7), pneumothorax (n = 2),
      pericarditis (n = 2), dislodged sternal bar (n = 3), and mildly hypertrophic scar
      (n = 12). Mean hospitalization was 2.9 days; mean blood loss was 122 mL. Pain was
      mild and of short duration (intravenous analgesics were used a mean of 2.1 days).
      There were no deaths. With a mean follow-up of 4.3 years, 109 of 113 respondents
      had a very good or excellent result. CONCLUSIONS: Although technically more
      difficult than in children, pectus deformities may be repaired in adults with low
      morbidity, short hospital stay, and very good physiologic and cosmetic results.

PMID- 12192318
TI  - Pretransplant model to predict posttransplant survival in liver transplant
      patients.
AB  - OBJECTIVE: To develop a prognostic model that determines patient survival
      outcomes after orthotopic liver transplantation (OLT) using readily available
      pretransplant variables. SUMMARY BACKGROUND DATA: The current liver organ
      allocation system strongly favors organ distribution to critically ill recipients
      who exhibit poor survival outcomes following OLT. A severely limited organ
      resource, increasing waiting list deaths, and rising numbers of critically ill
      recipients mandate an organ allocation system that balances disease severity with
      survival outcomes. Such goals can be realized only through the development of
      prognostic models that predict survival following OLT. METHODS: Variables that
      may affect patient survival following OLT were analyzed in hepatitis C (HCV)
      recipients at the authors' center, since HCV is the most common indication for
      OLT. The resulting patient survival model was examined and refined in HCV and non
      HCV patients in the United Network for Organ Sharing (UNOS) database. Kaplan
      Meier methods, univariate comparisons, and multivariate Cox proportional hazard
      regression were employed for analyses. RESULTS: Variables identified by
      multivariate analysis as independent predictors for patient survival following
      primary transplantation of adult HCV recipients in the last 10 years at the
      authors' center were entered into a prognostic survival model to predict patient
      survival. Accordingly, mortality was predicted by 0.0293 (recipient age) + 1.085
      (log10 recipient creatinine) + 0.289 (donor female gender) + 0.675 urgent UNOS -
      1.612 (log10 recipient creatinine times urgent UNOS). The above variables, in
      addition to donor age, total bilirubin, prothrombin time (PT), retransplantation,
      and warm and cold ischemia times, were applied to the UNOS database. Of the
      46,942 patients transplanted over the last 10 years, 25,772 patients had complete
      data sets. An eight-factor model that accurately predicted survival was derived.
      Accordingly, the mortality index posttransplantation = 0.0084 donor age + 0.019
      recipient age + 0.816 log creatinine + 0.0044 warm ischemia (in minutes) + 0.659
      (if second transplant) + 0.10 log bilirubin + 0.0087 PT + 0.01 cold ischemia (in
      hours). Thus, this model is applicable to first or second liver transplants.
      Patient survival rates based on model-predicted risk scores for death and
      observed posttransplant survival rates were similar. Additionally, the model
      accurately predicted survival outcomes for HCV and non-HCV patients. CONCLUSIONS:
      Posttransplant patient survival can be accurately predicted based on eight
      straightforward factors. The balanced application of a model for liver transplant
      survival estimate, in addition to disease severity, as estimated by the model for
      end-stage liver disease, would markedly improve survival outcomes and maximize
      patients' benefits following OLT.

PMID- 12192319
TI  - Vagal-sparing esophagectomy: a more physiologic alternative.
AB  - OBJECTIVE: To evaluate the function of the vagal nerves and the gastric reservoir
      after vagal-sparing esophagectomy. SUMMARY BACKGROUND DATA: Esophagectomy as
      currently performed includes division of the vagal nerves and surgical alteration
      of the stomach, with attendant postoperative dumping, diarrhea, reduced meal
      capacity, and weight loss. Vagal-sparing esophagectomy has been introduced as a
      technique for removal of the esophagus while preserving the vagal nerves and
      gastric reservoir. The procedure is touted as having a low morbidity and is
      applicable to patients with end-stage benign or early malignant disease. METHODS:
      A random sample of 15 patients at a median of 20 months after a vagal-sparing
      esophagectomy was compared to 23 asymptomatic normal subjects; 10 randomly
      selected patients, 29 months after esophagogastrectomy with colon interposition;
      and 10 randomly selected patients, 47 months after standard esophagectomy with
      gastric pull-up. Gastric mucosal acidification was tested with Congo red
      staining. Vagal secretory function was measured by gastric acid output and
      pancreatic polypeptide response to sham feeding. Vagal motor function was
      assessed by a technetium gastric emptying scan and a questionnaire to evaluate
      dumping and diarrhea. Gastric reservoir function was evaluated by measuring meal
      capacity and postoperative changes in body mass index. RESULTS: Vagal-sparing
      esophagectomy preserved the function of the vagi, as evident by an increase in
      gastric acid output, a rise in serum pancreatic polypeptide following sham
      feeding, and preservation of normal postoperative gastric emptying in 70% of the
      patients. After vagal-sparing esophagectomy, patients were free of dumping and
      diarrhea and were analogous to normal subjects in meal capacity but had a slight
      reduction in the speed of eating. CONCLUSIONS: Vagal-sparing esophagectomy
      preserves gastric secretory, motor, and reservoir function. Postoperatively,
      patients have normal alimentation, bowel regulation, and no weight loss. It is an
      ideal procedure for patients with end-stage benign disease, Barrett's esophagus
      with high-grade dysplasia, or esophageal carcinoma limited to the lamina propria.

PMID- 12192320
TI  - Efficacy of multiagent herpes simplex virus amplicon-mediated immunotherapy as
      adjuvant treatment for experimental hepatic cancer.
AB  - OBJECTIVE: To evaluate the use of herpes simplex viral (HSV) amplicon vectors for
      production of tumor vaccines and to determine if such vaccines expressing
      combinations of immunostimulatory agents may be effective in the treatment of
      experimental liver cancer. METHODS: A hepatic metastatic tumor model using CT-26
      colorectal cancer in syngeneic Balb/C mice was utilized. Tumor vaccines were
      produced by brief (20 minutes) exposure of irradiated tumor cells to herpes
      amplicon vectors carrying the transgene for RANTES, B7.1, or GM-CSF. The
      antitumor efficacy of vaccination using tumor cells secreting GM-CSF (single
      agent) or a combination of RANTES/B7.1/GM-CSF (multiagent) was tested. The effect
      of 60% hepatectomy or T-cell depletion was also tested in this model. RESULTS: In
      vitro assays confirmed high-level cytokine or costimulatory molecule production
      by cells transduced with amplicons. Antitumor efficacy was observed with single
      agent or multiagent treatment. Without hepatectomy, immunization with single
      agent or multiagent vaccine therapy appears equivalent. When administered in the
      setting of hepatectomy, multiagent regimens produced a higher cure rate than
      single-agent therapy (50% vs. 12.5%, =.03). Animals treated with GM-CSF alone had
      an average nodule count of 40 +/- 19 ( <.006 vs. Hep control 232 +/- 30), while
      animals treated with multiagent therapy had an average nodule count of 11 +/- 7 (
      <.0004 vs. control). CD4 and CD8 lymphocyte blockade abrogated observed efficacy,
      confirming a lymphocyte-mediated response. CONCLUSIONS: Tumor vaccines produced
      using HSV amplicon-mediated gene transfer may be useful in the treatment of liver
      malignancies. In the setting of hepatectomy, multiagent vaccine therapy offers an
      advantage over single-agent therapy. These data encourage consideration of such
      HSV-based neoadjuvant immunotherapy for treatment of liver malignancies.

PMID- 12192321
TI  - The National Surgical Quality Improvement Program in non-veterans administration
      hospitals: initial demonstration of feasibility.
AB  - OBJECTIVE: To assess the feasibility of implementing the National Surgical
      Quality Improvement Program (NSQIP) methodology in non-VA hospitals. SUMMARY
      BACKGROUND DATA: Using data adjusted for patient preoperative risk, the NSQIP
      compares the performance of all VA hospitals performing major surgery and
      anonymously compares these hospitals using the ratio of observed to expected
      adverse events. These results are provided to each hospital and used to identify
      areas for improvement. Since the NSQIP's inception in 1994, the VA has reported
      consistent improvements in all surgery performance measures. Given the success of
      the NSQIP within the VA, as well as the lack of a comparable system in non-VA
      hospitals, this pilot study was undertaken to test the applicability of the NSQIP
      models and methodology in the nonfederal sector. METHODS: Beginning in 1999,
      three academic medical centers (Emory University, Atlanta, GA; University of
      Michigan, Ann Arbor, MI; University of Kentucky, Lexington, KY) volunteered the
      time of a dedicated surgical nurse reviewer who was trained in NSQIP methodology.
      At each academic center, these nurse reviewers used NSQIP protocols to abstract
      clinical data from general surgery and vascular surgery patients. Data were
      manually collected and then transmitted via the Internet to a secure web site
      developed by the NSQIP. These data were compared to the data for general and
      vascular surgery patients collected during a concurrent time period (10/99 to
      9/00) within the VA by the NSQIP. Logistic regression models were developed for
      both non-VA and VA hospital data. To assess the models' predictive values, C
      indices (0.5 = no prediction; 1.0 = perfect prediction) were calculated after
      applying the models to the non-VA as well as the VA databases. RESULTS: Data from
      2,747 (general surgery 2,251; vascular surgery 496) non-VA hospital cases were
      compared to data from 41,360 (general surgery 31,393; vascular surgery 9,967) VA
      cases. The bivariate relationships between individual risk factors and 30-day
      mortality or morbidity were similar in the non-VA and VA patient populations for
      over 66% of the risk variables. C-indices of 0.942 (general surgery), 0.915
      (vascular surgery), and 0.934 (general plus vascular surgery) were obtained
      following application of the VA NSQIP mortality model to the non-VA patient data.
      Lower C-indices (0.778, general surgery; 0.638, vascular surgery; 0.760, general
      plus vascular surgery) were obtained following application of the VA NSQIP
      morbidity model to the non-VA patient data. Although the non-VA sample size was
      smaller than the VA, preliminary analysis suggested no differences in risk
      adjusted mortality between the non-VA and VA cohorts. CONCLUSIONS With some
      adjustments, the NSQIP methodology can be implemented and generates reasonable
      predictive models within non-VA hospitals.

PMID- 12192323
TI  - Effect of a specialized amino acid mixture on human collagen deposition.
AB  - OBJECTIVE: To examine the effect of arginine, beta-hydroxy-beta-methylbutyrate
      (HMB), and glutamine supplementation on wound collagen accumulation in a double
      blind, randomized study. SUMMARY BACKGROUND DATA: Control of wound collagen
      synthesis has been an elusive goal for clinicians and scientists alike. In many
      clinical instances, it is desired to increase collagen deposition as a means of
      enhancing wound strength and integrity. Arginine, a semiessential amino acid, has
      been shown to increase wound collagen accumulation in rodents and humans. HMB, a
      metabolite of leucine, regulates muscle proteolysis in animals and humans and
      increases collagen deposition in rodents. METHODS: Thirty-five healthy,
      nonsmoking human volunteers 70 years or older were enrolled and underwent
      subcutaneous implantation of two small, sterile polytetrafluoroethylene (PTFE)
      tubes into the deltoid region under strict aseptic techniques. The tubes were 1
      mm in diameter and 6 cm in length with pore size of 90 to 120 microm to allow
      optimal ingrowth of fibroblasts and the deposition of matrix. Eighteen volunteers
      (mean age 75.4 years; 2 men, 16 women) were randomized to receive daily
      supplementation of 14 g arginine, 3 g HMB, and 14 g glutamine (total nitrogen
      3.59 g) in two divided doses. The control group (n = 17; mean age 75.3 years; 6
      men, 11 women) received an isonitrogenous, isocaloric supplementation of
      nonessential amino acids. Catheters were removed at 7 and 14 days
      postimplantation and analyzed for hydroxyproline (OHP, nmol/cm catheter, an index
      of collagen accumulation) and alpha-amino nitrogen (alpha-AN, mmol/cm, an index
      of total protein deposition). RESULTS: Supplements were well tolerated, without
      any reported side effects. Supplementation with the specialized amino acid
      mixture led to a significant rise in plasma arginine and ornithine levels. The
      specialized amino acid supplement led to a significant increase in collagen
      deposition (as reflected by OHP content) in the PTFE tubes without an effect on
      total protein accumulation. CONCLUSIONS: Collagen synthesis is significantly
      enhanced in healthy elderly volunteers by the oral administration of a mixture of
      arginine, HMB, and glutamine. This provides a safe nutritional means for
      increasing wound repair in patients.

PMID- 12192322
TI  - Pancreaticoduodenectomy with or without distal gastrectomy and extended
      retroperitoneal lymphadenectomy for periampullary adenocarcinoma, part 2:
      randomized controlled trial evaluating survival, morbidity, and mortality.
AB  - OBJECTIVE: To evaluate, in a prospective, randomized single-institution trial,
      the end points of operative morbidity, operative mortality, and survival in
      patients undergoing standard versus radical (extended) pancreaticoduodenectomy.
      SUMMARY BACKGROUND DATA: Numerous retrospective reports and a few prospective
      randomized trials have suggested that the performance of an extended
      lymphadenectomy in association with a pancreaticoduodenal resection may improve
      survival for patients with pancreatic and other periampullary adenocarcinomas.
      METHODS: Between April 1996 and June 2001, 299 patients with periampullary
      adenocarcinoma were enrolled in a prospective, randomized single-institution
      trial. After intraoperative verification (by frozen section) of margin-negative
      resected periampullary adenocarcinoma, patients were randomized to either a
      standard pancreaticoduodenectomy (removing only the peripancreatic lymph nodes en
      bloc with the specimen) or a radical (extended) pancreaticoduodenectomy (standard
      resection plus distal gastrectomy and retroperitoneal lymphadenectomy). All
      pathology specimens were reviewed, fully categorized, and staged. The
      postoperative morbidity, mortality, and survival data were analyzed. RESULTS: Of
      the 299 patients randomized, 5 (1.7%) were subsequently excluded because their
      final pathology failed to reveal periampullary adenocarcinoma, leaving 294
      patients for analysis (146 standard vs. 148 radical). The two groups were
      statistically similar with regard to age (median 67 years) and gender (54% male).
      All the patients in the radical group underwent distal gastric resection, while
      86% of the patients in the standard group underwent pylorus preservation (
      <.0001). The mean operative time in the radical group was 6.4 hours, compared to
      5.9 hours in the standard group ( =.002). There were no significant differences
      between the two groups with respect to intraoperative blood loss, transfusion
      requirements (median zero units), location of primary tumor (57% pancreatic, 22%
      ampullary, 17% distal bile duct, 3% duodenal), mean tumor size (2.6 cm), positive
      lymph node status (74%), or positive margin status on final permanent section
      (10%). The mean total number of lymph nodes resected was significantly higher in
      the radical group. Of the 148 patients in the radical group, only 15% (n = 22)
      had metastatic adenocarcinoma in the resected retroperitoneal lymph nodes, and
      none had retroperitoneal nodes as the only site of lymph node involvement. One
      patient in the radical group with negative pancreaticoduodenectomy specimen lymph
      nodes had a micrometastasis to one perigastric lymph node. There were six
      perioperative deaths (4%) in the standard group versus three perioperative deaths
      (2%) in the radical group ( = NS). The overall complication rates were 29% for
      the standard group versus 43% for the radical group ( =.01), with patients in the
      radical group having significantly higher rates of early delayed gastric emptying
      and pancreatic fistula and a significantly longer mean postoperative stay. With a
      mean patient follow-up of 24 months, there were no significant differences in 1-,
      3-, or 5-year and median survival when comparing the standard and radical groups.
      CONCLUSIONS: Radical (extended) pancreaticoduodenectomy can be performed with
      similar mortality but some increased morbidity compared to standard
      pancreaticoduodenectomy. The data to date fail to indicate that a survival
      benefit is derived from the addition of a distal gastrectomy and retroperitoneal
      lymphadenectomy to a pylorus-preserving pancreaticoduodenectomy.

PMID- 12192324
TI  - Treatment outcomes of resected esophageal cancer.
AB  - OBJECTIVE: To assess the evolution of treatment and outcome for resected
      esophageal cancer at a single institution. SUMMARY BACKGROUND DATA: Strategies
      for optimizing the treatment of resected esophageal cancer continue to evolve
      over time. The outcomes of these evolving treatments in the context of improved
      diagnostic staging and changing epidemiology have not been carefully analyzed in
      a single institution. METHODS: One thousand ninety-seven consecutive patients
      with primary esophageal cancer underwent surgery during the period 1970 to 2001.
      Nine hundred ninety-four patients underwent curative esophagectomy and were
      analyzed for changing demographics. Eight hundred seventy-nine patients who did
      not have systemic metastases and survived the perioperative period were assessed
      by multivariate analysis for factors associated with long-term survival. RESULTS:
      During the study period the overall median survival increased from 17 to 34
      months, and combined hospital and 30-day mortality decreased from 12% to 6%. The
      R0 resection rate increased from 78 to 94%, and adenocarcinoma replaced squamous
      cell carcinoma as the predominant histology (83% vs. 17%). No change in survival
      with time was noted for patients treated with surgery alone having the same
      postoperative pathologic stage (pTNM). An increased proportion of patients had
      preoperative chemoradiation in the last 4 years of the study (59% vs. 2%).
      Preoperative chemoradiation was associated with a longer survival and increased
      likelihood of achieving a complete resection. Multivariate analysis showed that
      long-term survival was associated with a complete resection and the preoperative
      staging strategy used, while the use of preoperative chemoradiation was the most
      significant factor associated with ability to achieve an R0 esophageal resection.
      CONCLUSIONS: This study shows favorable trends in the survival of patients with
      resected esophageal cancer over time. The increased use of preoperative
      chemoradiation, better preoperative staging, and other time-dependent factors may
      have contributed to the observed increase in survival.

PMID- 12192326
TI  - Bereavement support: something for everyone?

PMID- 12192325
TI  - Prospective screening for blunt cerebrovascular injuries: analysis of diagnostic
      modalities and outcomes.
AB  - OBJECTIVE: To prospectively examine outcomes associated with an aggressive
      screening protocol for blunt cerebrovascular injury (BCVI), and to compare the
      accuracy of computed tomographic angiography (CTA) and magnetic resonance
      angiography (MRA) versus conventional angiography with respect to BCVI diagnosis.
      SUMMARY BACKGROUND DATA: In the past 5 years, BCVI (carotid and vertebral
      arteries) has been recognized with increasing frequency. Initial studies
      described blunt carotid injuries and their associated morbidity, while more
      recent reports have established the devastating potential of blunt vertebral
      injuries. It has been suggested that early diagnosis and anticoagulation will
      improve outcomes and that less-invasive diagnostic techniques than conventional
      angiography are desirable for screening. However, there are neither established
      screening criteria nor studies comparing optimal diagnostic modalities. METHODS:
      The screened population included all patients with cervical spine fractures,
      LeFort II or III facial fractures, Horner's syndrome, skull base fractures
      involving the foramen lacerum, neck soft tissue injury, or neurological
      abnormalities unexplained by intracranial injuries. Patients underwent screening
      with four-vessel cerebral angiography. During the first half of the study,
      patients also underwent helical CTA. Selected patients during this same period
      underwent MRA. At the time of diagnosis, anticoagulant or antiplatelet therapy
      was instituted unless clinically contraindicated. Results of this screening
      protocol were compared to a previously published cohort with cerebrovascular
      injuries (1995-1999) from the authors' institution. RESULTS: Two hundred sixteen
      patients were screened over a 2-year period (3.5% of all blunt trauma
      admissions). Angiography identified 24 patients with carotid artery injuries
      (CAI) and 43 patients with vertebral artery injuries (VAI) for an overall
      screening yield of 29%. While the incidence of CAI remained similar between the
      current study and the previous study group, the incidence of VAI diagnosis
      increased. Stroke rates in those with CAI were also similar between the two
      periods. The stroke rate in VAI, however, was markedly lower at 0% as compared to
      14% in the previous group. Comparison of CTA and MRA with cerebral angiography in
      143 patients demonstrated sensitivities of 47% and 50%, respectively, for CAI;
      sensitivities were 53% (CTA) and 47% (MRA) for VAI. CONCLUSIONS: Aggressive
      screening of patients with blunt head and neck trauma identified an incidence of
      BCVI in 1.03% of blunt admissions. Early identification, which led to early
      treatment, significantly reduced stroke rates in patients with VAI, but provided
      no outcome improvement with CAI. More encompassing screening may be required to
      improve outcomes for patients with CAI. However, less-invasive diagnostic
      techniques (CTA and MRA) are inadequate for screening. Technological advances are
      necessary before abandonment of conventional angiography, which remains the
      standard for diagnosis.

PMID- 12192327
TI  - The management of constipation in people with advanced cancer.
AB  - Constipation represents a significant problem for people with advanced cancer. It
      ranks in the top three most uncomfortable symptoms experienced, causing pain and
      anorexia that ultimately result in misery. The negative impact upon the quality
      of life of the patient and their carers is significant. The key to the provision
      of effective care lies in the informed application of the nursing process,
      underpinned by a sound knowledge base in relation to the management of
      constipation. Theoretical knowledge enables appropriate preventative
      interventions to be planned in collaboration with other members of the
      multidisciplinary team. When preventative measures are not applied or are
      unsuccessful, informed assessment and care planning enables appropriate
      interventions to be applied in order to resolve constipation. This article will
      discuss the causes and management of constipation. The discussion focuses on
      assessment, setting goals with the patient and their carers, planning appropriate
      nursing interventions to support medical interventions and evaluating clinical
      outcomes.

PMID- 12192328
TI  - Fighting Spirit: a psychoeducational group for younger women with breast cancer.
AB  - Overall cancer survival rates in the United Kingdom are demonstrating a continual
      and progressive increase. Women diagnosed with breast cancer contribute to 28% of
      the 45% of all female cancers in the higher survival band (Coleman et al, 1999).
      As medical therapies strive to cure or extend the survival of patients diagnosed
      with cancer the quality of their cancer experience becomes paramount. Fighting
      Spirit is a support group that aims to reduce psychological morbidity in young
      women diagnosed with breast cancer. It promotes an optimistic attitude and a wish
      to participate and learn about treatment modalities while carrying on a normal
      life despite having cancer. The programme provides supportive therapy for both
      curative and palliative care. This article offers a rationale for the group
      intervention, describes the model used and the programme content. The
      facilitators' experience of running the group is also discussed.

PMID- 12192329
TI  - Palliative care nurses' perceptions of good and bad deaths and care expectations:
      a qualitative analysis.
AB  - Individuals who are involved with the death of a person with a terminal illness
      will often classify the death as either 'good' or 'bad'. Families and healthcare
      practitioners assess many factors when determining their 'success' or 'failure'
      in assisting someone in the terminal phase. Palliative care nurses are
      particularly vulnerable to self-assessments about care of the dying, because
      death is a daily occurrence. Feelings of failure, unmet expectations and feeling
      of regret about not being able to prevent a traumatic death may be a source of
      stress for palliative care nurse and may affect their abilities to function
      effectively. This article reports the findings of a study involving interviews
      with 20 palliative care nurses to determine their perceptions of a good and bad
      death. The study also examined the expectations they hold of themselves and that
      they believe others hold of them in helping patients to attain a good death.
      Clinical implications are discussed based on these findings.

PMID- 12192330
TI  - Relating palliative care principles to the promotion of undisturbed sleep in a
      hospice setting.
AB  - Nurses working at night have a specific role in supporting sleep and promoting
      rest and comfort. Sometimes the role of the night duty nurse in promoting sleep
      and comfort is taken for granted. One author's experience of working as a night
      duty nurse led to reflection on her responsibilities in improving practice and
      addressing the sleep-related needs of patients in a palliative care setting.
      Following a literature review, it was clear that there are very few publications
      on sleep disturbance in palliative care. Using the four principles of palliative
      care (Aranda, 1998a), the authors construct a series of strategies to prevent and
      manage sleep issues.

PMID- 12192331
TI  - Developing empathy to improve patient care: a pilot study of cancer nurses.
AB  - Empathy has been identified as an important communication skill that can improve
      psychological outcomes for patients with cancer and palliative care patients; as
      such there is a need for cancer nurses to be empathic. The majority of research
      that has been carried out has been concerned with the definition and measurement
      of empathy. Exploration into the concept of empathy has shown that there is a
      need to examine the nature of it and to identify exactly where it succeeds and
      fails. The questions of how empathy is nurtured and sustained and under what
      conditions it flourishes and diminishes need to be addressed. This study aimed to
      investigate how cancer nurses interpret and acquire empathy, and to identify the
      conditions that influence it. It was also important to establish what cancer
      nurses considered to be the benefits and disadvantages of expressing empathy. The
      findings demonstrated that nurses are aware of the concept of empathy and do use
      their empathic skills; however, there are barriers that could inhibit the
      expression of empathy, including lack of time, poor environment and communication
      difficulties. This study highlights the recognition of empathy as a discrete
      communication skill and the need for more structured courses.

PMID- 12192332
TI  - The NHS Plan: does it meet older people's needs?

PMID- 12192333
TI  - The information technology challenge for the NHS.

PMID- 12192334
TI  - Health visitors' knowledge and attitudes relating to HIV and AIDS.
AB  - Infection with human immunodeficiency virus (HIV) is increasing in the
      heterosexual community and people already affected by HIV are living longer. As a
      result, health visitors will be more involved in caring for people with HIV and
      acquired immune deficiency syndrome (AIDS). The aim of this study was to assess
      the knowledge level of health visitors about HIV infection and AIDS, and to
      identify some of the attitudes held by them concerning AIDS and the variety of
      symptoms that can occur in HIV positive individuals (AIDS related complex) before
      they have actually developed AIDS. The influence of AIDS-related education and
      the experience of caring for affected patients on health visitors' knowledge of
      the disease was assessed. The attitudes of carers towards these patients were
      also ascertained. All heath visitors (n = 88) working in the Merton and Sutton
      Community Healthcare Trust were invited to participate in a questionnaire survey.
      Fifty-five health visitors participated. Knowledge relating to HIV and AIDS was
      good, but the majority of respondents felt they did not have all the information
      they needed about HIV and AIDS. Almost one-quarter of respondents had cared for a
      client who was either HIV positive or had AIDS. Overall, the findings were quite
      encouraging. However, further education, training, and support were identified as
      necessary. These shortfalls need to be addressed in order to fully assist health
      visitors in their role of caring for clients and families affected by HIV and
      AIDS.

PMID- 12192335
TI  - Public health and the role of the nurse: the need for greater clarity.
AB  - There is evidence that public health is currently taking centre stage in the
      challenge to improve the population's health. This represents a change from the
      1980s and 1990s where health promotion was the dominant concept among community
      nurses. Public health means different things to different people and while nurses
      have a role to play, there is a need to be more precise about their specific
      contribution. The creation of public health nursing posts across the UK is
      contribution to this confusion, as there is little emerging consensus as to what
      professionals in these posts should do. At present, there does not appear to be a
      dominant strategy or model of working. A preliminary analysis of job
      advertisements for public health nursing posts indicates a requirement for a
      'supercharged' health visitor to work in a specific area to provide a link
      between the professional and lay communities. The emphasis is on community
      development with little on population health. Government policy on public health
      clearly highlights the important role of nurses in contributing to the public
      health agenda. The current role and function of public health nursing posts may
      not allow them to be classed as specialist public health nurses/nursing and to
      provide educational opportunities for nurses to develop the knowledge and skills
      which will enable them to work alongside medical and other healthcare colleagues
      in the pursuit of specialist public health practitioner status.

PMID- 12192336
TI  - A podiatrist's view of community diabetic foot management.
AB  - The diabetic foot is an enormous burden to the patient, society and to the NHS.
      This article offers a podiatrist's view of the diabetic foot: the principles
      behind the disease process, the management of diabetic foot complications and how
      problems can be avoided. The major contributing factors of diabetic foot ulcers
      are discussed, the role of the podiatrist described, and the principles of
      screening and community-based management of ulcers outlined. Education and
      communication are highlighted as key elements in successful diabetic foot
      management.

PMID- 12192337
TI  - Management of the older person with diabetes in the community.
AB  - As the incidence of diabetes increases in the UK, community nurses will have
      increasingly larger caseloads of elderly patients with diabetes. It is important
      that nurses assess the patient's understanding of the disease and its treatment.
      The aim of good diabetic control is to reduce morbidity from the complications of
      the disease. Factors that affect the patients' quality of life; the patients'
      ability to manage their condition; and the importance of providing education and
      support for both the patients and their carers are discussed. The importance of
      diet, blood glucose monitoring and taking diabetic medication appropriately are
      explained.

PMID- 12192339
TI  - Some new and important clues to the causes of colic.
AB  - Colic, or persistent unexplained crying in infants, is commonly encountered by
      health professionals. While not harmful to the child, it can place a great deal
      of stress on the parents and family. The cause of colic has not been definitively
      identified. Transient lactose intolerance, as a result of inadequate production
      of the enzyme lactase, is one possibility. Studies have shown a reduced crying
      time when formula or breast milk is incubated with lactase. Colief Infant Drops
      consist of lactase in a glycerol and water solution which, when added to formula
      or breast milk, converts lactose to simple sugars and makes the feed more easily
      digestible.

PMID- 12192338
TI  - Crown II: the implications of nurse prescribing for practice nursing.
AB  - Certain limited prescribing rights have now been granted to district nurses and
      health visitors. Proposals to extend prescribing rights to other health
      professionals have recently been put forward in the Review of Prescribing. Supply
      and Administration of Medicines (DoH, 1999). Practice nurses are one group who
      are likely to apply for such rights. This article reports on selected findings
      from a small-scale qualitative study designed to investigate the current and
      potential future of practice nurse in prescribing. It was found that practice
      nurses exercise considerable influence over prescribing in diverse therapeutic
      areas within general practice. However, it may be difficult to accommodate the
      prescribing requirements inherent in such a broad scope of practice within the
      framework of the present proposals. Important issues of accountability and
      patient safety are raised, and recommendations made for policy, research and
      education.

PMID- 12192340
TI  - Preparing the next generation for citizenship.

PMID- 12192341
TI  - Let's give a little for our common purpose.

PMID- 12192342
TI  - Malignant fungating wounds: assessment and management.
AB  - Approximately 5-10% of patients with metastatic cancer will develop a fungating
      wound. The disfiguring or unpleasant nature of these wounds can lead to complex
      psychosocial problems in patients, which mean that many will seek medical
      assistance only when the wound is advanced. Curative treatment is often not an
      option, although a range of palliative treatments may be tried. When the tumour
      does not respond to these treatments the patient will be left with a chronic
      complex wound with local wound management as the only option. It is at this time
      that the community nurse usually becomes involved with the patient. This article
      discusses the assessment of patients with fungating wounds in the community,
      taking into consideration the immense psychological distress that they can cause.
      It highlights factors that need to be taken into consideration when assessing
      these complex wounds. Many of them are heavily exuding, malodorous and bleed
      easily. Strategies that focus on managing these symptoms are explored and
      recommendations for clinical practice are made.

PMID- 12192343
TI  - Domestic violence and anger: what can primary care nurses do?
AB  - Patients with anger problems can cause difficulties for themselves, their
      families and society. Though psychological treatments are available, they are not
      always accessible. In order to help the victims of domestic violence, we focus
      here on working with perpetrators of violence. This article offers some
      statistics about the extent of the problem. It discusses difficulties in
      motivating patients for therapy and describes the cognitive model of anger. A
      number of intervention strategies based on this model are then discussed. The
      purpose is to assist clinicians with less experience of this patient group to
      help their patients minimize the frequency and severity of the anger incidents.
      Pointers for good practice are outlined.

PMID- 12192345
TI  - Nutrition and diabetes control: advice for non-dietitians.
AB  - Diabetes mellitus affects 2-4% of the UK population and its prevalence is
      predicted to double by 2010. It has been widely acknowledged that dietary therapy
      can reduce the risk of complications in people with diabetes. However, as there
      are insufficient diabetes specialist dietitians to deliver dietary advice to all
      people with diabetes, the burden of care will fall on the primary care team.
      Dietary advice given to people with diabetes by healthcare professionals needs to
      be consistent. As recommendations change with new evidence, professionals have a
      duty to update their knowledge. This article reviews current nutritional
      recommendations from the UK, Europe and the USA and offers suggestions for
      translating dietary theory into practice. It emphasizes the importance of an
      individual approach, taking into account usual eating patterns, lifestyle, age,
      culture and medication.

PMID- 12192344
TI  - GPs' perceptions of the nurse practitioner role in primary care.
AB  - The role of nurse practitioner (NP) is increasingly integrated into the primary
      healthcare team, yet there remains some confusion among general practitioners
      about what the role entails. Following on from previous work (Carr et al, 2001),
      this study indicates that the majority of GPs surveyed were supportive of the
      integration of the NP role in primary care, both to help reduce the GPs' workload
      and more importantly to give the patient a choice of who to consult. However,
      there was some difference in opinion as to what tasks were most appropriately
      linked to the NP role. This may be due to the GPs' lack of knowledge and
      experience of the role. There were also some reservations about the financial
      cost of training and employing NPs. If the health needs of the population are to
      be met and high quality, seamless care provided, the NP could provide a solution.

PMID- 12192346
TI  - Chronic non-cancer pain in older people: current evidence for prescribing.
AB  - Chronic pain is a serious problem for many older people, yet its management in
      this population is often less than satisfactory. The high incidence of toxicity
      and side effects with some medications and irrational fears of opioid dependence
      are significant barriers to effective pain management. In this article, the
      research evidence relating to these issues is examined, and their impact on nurse
      prescribing considered. More studies are needed to assess the veracity of
      opposing arguments, and to support effective assessment and prescribing by
      nurses.

PMID- 12192347
TI  - Preventing avoidable hospital admission of older people.
AB  - The National Service Framework for Older People (Department of Health, 2001)
      stresses the importance of preventing unnecessary hospital admissions for older
      people. Such admissions arise when there is inadequate health and social support
      available in the community to meet the needs of this age group. This article
      reports on a study designed to evaluate the effectiveness of a programme of
      enhanced primary care support intended to reduce the risk of hospital admission
      for people aged 75 years and above. Nineteen patients out of a possible 322 in
      one GP practice were judged by GPs and district nurses to be "at risk" of
      avoidable hospital admission. All at-risk patients were visited by a GP or
      district nurse to review their needs for enhanced support, six patients
      subsequently accepting a referral for additional support. No statistically
      significant difference in the number of hospital admissions in the intervention
      group was observed compared with a group of patients with similar demographic
      characteristics but deemed not to be at such high risk, suggesting that the
      intervention might have been effective in reducing the number of avoidable
      hospital admissions.

PMID- 12192348
TI  - The nation is getting fatter.

PMID- 12192349
TI  - Reliability of assigning correct current procedural terminology-4 E/M codes.
AB  - STUDY OBJECTIVES: We determine the degree of interagency and intra-agency
      agreement on Current Procedural Terminology-4 (CPT-4) coding levels for emergency
      department medical records. We hypothesized that the level of agreement among
      coding agencies would be poor, but the distribution of codes would be similar and
      not significantly different. METHODS: We performed a prospective observational
      study consisting of 3 separate randomized, blinded trials: 2 interagency
      comparisons and 1 intra-agency comparison. The setting was 2 suburban academic
      EDs. In the 2 interagency audits, 4 coding agencies were used. In the intra
      agency comparison, we used 5 individual coders from within our own internal
      agency. The main outcome measures were the level of agreement not due to chance
      estimated with the multiple-rater weighted kappa statistic and the Kendall tau-b.
      We measured the distribution of codes by agency or by individual coders with the
      chi(2) test. RESULTS: Our sample for the 2 interagency audits consisted of 194
      and 195 records, respectively. We observed poor agreement in the level of coding
      assigned to individual charts among the 4 coding agencies, with kappa values of
      0.28 (95% confidence interval [CI] 0.275 to 0.285) and 0.287 (95% CI 0.283 to
      0.291). Our intra-agency comparison consisted of 100 records. The agreement in
      the intra-agency review was significantly better but still fair (kappa=0.436; 95%
      CI 0.428 to 0.444). The distribution of CPT-4 codes was significantly different
      for all 3 comparisons (P <.001). CONCLUSION: For our patient population, group of
      physicians, and methods of documentation, we identified poor-to-fair agreement in
      coding of emergency charts between coding agencies. Only fair agreement was
      measured in the intra-agency sample. The distribution of assigned CPT-4 codes was
      significantly different in each comparison. These findings have important
      financial and legal implications regarding the reliability of coding methods.

PMID- 12192350
TI  - E/M coding and the OIG: not so reliable after all.

PMID- 12192351
TI  - The accuracy of noncontrast helical computed tomography versus intravenous
      pyelography in the diagnosis of suspected acute urolithiasis: a meta-analysis.
AB  - STUDY OBJECTIVES: We determine the accuracy of noncontrast helical computed
      tomography (NHCT) compared with that of intravenous pyelography (IVP) in
      diagnosing acute urolithiasis. METHODS: Computerized searches of MEDLINE and
      EMBASE were combined with hand reviews of major journals and of articles from
      reference lists. Articles were assessed according to a priori criteria for
      inclusion. Study eligibility was independently assessed by 2 reviewers in a
      blinded fashion. Test results were combined and analysis of log-transformed data
      was conducted by using general linear models. RESULTS: No disagreement was found
      between the 2 investigators in terms of articles that met the inclusion criteria
      or between the results of the studies. Four studies involving a total of 296
      patients met all of the a priori criteria. The pooled positive likelihood ratios
      (LR+) for NHCT and IVP are 23.15 (95% confidence interval [CI] 11.53 to 47.23)
      and 9.32 (95% CI 5.23 to 16.61), respectively. The pooled negative likelihood
      ratios (LR-) for NHCT and IVP are 0.05 (95% CI 0.02 to 0.15) and 0.33 (95% CI
      0.23 to 0.48), respectively. The differences between NHCT and IVP were
      statistically significant for both LR+ (P =.046) and LR- (P =.013). Differences
      among trials were not statistically significant in either analysis (P =.125 for
      LR+; P =.114 for LR-). CONCLUSION: The studies analyzed consistently demonstrated
      NHCT to be superior to IVP in accurately diagnosing acute urolithiasis, and
      differences between the 2 tests for both LR+ and LR- were statistically
      significant.

PMID- 12192352
TI  - Validity of a decision rule to reduce cervical spine radiography in elderly
      patients with blunt trauma.
AB  - STUDY OBJECTIVES: A decision instrument based on 5 clinical criteria has been
      shown to be highly sensitive in selecting patients who require cervical spine
      imaging after blunt trauma, while simultaneously reducing overall imaging. We
      examine the performance of this instrument in the elderly and explore some of the
      common features of geriatric cervical spine injury (CSI). METHODS: The National
      Emergency X-radiography Utilization Study (NEXUS) was a prospective,
      observational, multicenter study conducted at 21 geographically diverse centers.
      We analyzed the performance of the NEXUS decision instrument among patients at
      least 65 years of age. RESULTS: The study group consisted of 2,943 (8.6%)
      geriatric patients, representing 8.6% of the entire NEXUS sample. The rate of CSI
      was twice as great in these patients as it was in nongeriatric patients (4.59%
      versus 2.19%). Odontoid fractures were particularly common in geriatric patients,
      accounting for 20% of geriatric fractures compared with 5% of nongeriatric
      fractures. The frequency of patients meeting NEXUS criteria was similar in the 2
      groups, with 14% of geriatric patients and 12.5% of nongeriatric patient
      classified as low risk. CSI occurred in only 2 low-risk geriatric patients, and
      these patients' injuries met our preset definition of a clinically insignificant
      injury. The sensitivity of the NEXUS decision instrument for clinically
      significant injury in the geriatric group was therefore 100% (95% confidence
      interval 97.1% to 100%). CONCLUSION: The prevalence of CSI, and especially
      odontoid fracture, is relatively increased among geriatric patients with blunt
      trauma. The NEXUS decision instrument can be applied safely to these patients,
      with an expected reduction in cervical imaging comparable with that achieved in
      nongeriatric patients.

PMID- 12192353
TI  - A randomized clinical trial: should the child with transient synovitis of the hip
      be treated with nonsteroidal anti-inflammatory drugs?
AB  - STUDY OBJECTIVES: The diagnosis of transient synovitis of the hip ("irritable
      hip") is made frequently in the pediatric emergency department. We hypothesized
      that an anti-inflammatory agent (ibuprofen syrup) would shorten the duration of
      symptoms. METHODS: Patients who were clinically diagnosed with transient
      synovitis of the hip in the ED between July 1997 and July 1998 were randomized in
      a double-blind, placebo-controlled trial to receive either ibuprofen syrup (10
      mg/kg 3 times a day for 5 days) or placebo. There were stringent exclusion
      criteria, and patients were only included if there was a low index of suspicion
      of more serious pathology. All patients had a hip ultrasonography performed at
      enrollment and at day 7. Symptoms were monitored by the use of a parental diary
      and clinical review. RESULTS: Forty patients were initially enrolled, but 4
      patients were subsequently excluded, leaving 17 patients in the ibuprofen group
      and 19 in the placebo group. Although symptoms resolved in more than 80% (30 of
      36) of patients in both groups by 7 days, the median duration of symptoms was
      shorter in the ibuprofen group (2 days compared with 4.5 days in the placebo
      group; P =.05 on Wilcoxon-Breslow test). The medication was well tolerated, with
      only minor gastrointestinal side effects being reported by 6 patients (4
      ibuprofen and 2 placebo). CONCLUSION: In this small study, ibuprofen shortened
      the duration of symptoms in children with a clinical diagnosis of transient
      synovitis of the hip.

PMID- 12192354
TI  - Initial oxygen saturation as a predictor of admission in children presenting to
      the emergency department with acute asthma.
AB  - BACKGROUND: Previous studies have looked at the relationship between initial
      oxygen saturation (SaO (2)) and the need for admission in children presenting
      with an acute asthma exacerbation. If initial SaO (2) value is indeed predictive
      of admission, then the admission process could be initiated sooner, and time
      spent in the emergency department could be potentially lessened. STUDY OBJECTIVE:
      The objective of the current study was to examine whether initial room air SaO
      (2) in children presenting to the ED with acute asthma is a reliable predictor of
      hospital admission. METHODS: This was a prospective multicenter study during 1997
      and 1998 at 44 North American EDs as part of the Multicenter Airway Research
      Collaboration. Inclusion criteria were physician diagnosis of acute asthma and
      age between 2 and 17 years. The association between hospital admission and SaO
      (2) was examined by using logistic regression. Likelihood ratios were used to
      assess the diagnostic value of SaO (2). RESULTS: Of the 1,184 children enrolled
      in the current study, 1,040 (88%) had a documented initial SaO (2) value on room
      air. The mean age of the cohort was 8+/-4 years, with a mean initial SaO (2) of
      95%+/-4%. Overall, 241 (23%) children were admitted to the hospital. The mean SaO
      (2) value of children admitted to the hospital was 93%+/-5% versus 96%+/-3% for
      those not admitted (P <.001). The admission rate decreased with increasing SaO
      (2); 73% (30/41) of children with an SaO (2) value of 88% or less were admitted
      versus 8% (7/88) with an SaO (2) value of 100%. In the logistic regression model,
      children with an SaO (2) value of 88% or less were 32 (95% confidence interval 11
      to 89) times more likely to be admitted than those with an SaO (2) value of 100%.
      The likelihood ratio for admission was 12 for children with an SaO (2) value of
      88% or less (42/1,040) but decreased to 4.6 for children with an SaO (2) value of
      91% or less (130/1,040) and 2.7 for children with an SaO (2) value of 94% or less
      (333/1,040). CONCLUSION: This large, clinical multicenter study does not support
      earlier findings that SaO (2) alone is a clinically useful predictor of hospital
      admission in children who present to the ED with acute asthma.

PMID- 12192356
TI  - Research into peer review and scientific publication: journals look in the
      mirror.

PMID- 12192355
TI  - Junctional ectopic tachycardia in association with blunt abdominal trauma.
AB  - Junctional ectopic tachycardia is recognized predominantly as a postoperative
      arrhythmia after surgery for congenital heart disease. Diagnosis and treatment
      distinguish it from more commonly observed mechanisms of supraventricular
      tachycardia. We present a case of junctional ectopic tachycardia that occurred in
      the setting of abdominal trauma caused by child abuse and then explore the
      significance of this arrhythmia in a patient with trauma.

PMID- 12192357
TI  - Graphical literacy: the quality of graphs in a large-circulation journal.
AB  - STUDY OBJECTIVES: We sought to characterize the quantity and quality of graphs in
      the Journal of American Medicine (JAMA), contrasting articles published in 1999
      with those published in 2000 after the addition of a dedicated tables and figures
      editor. We also sought to compare the quality of graphs in JAMA with the quality
      of graphs in Annals of Emergency Medicine. METHODS: Two reviewers independently
      assessed all graphs in original research articles from 12 randomly chosen issues
      of JAMA, 6 each from 1999 and 2000, using a standardized abstraction form. We
      noted graph type, clarity, and completeness and identified internal
      discrepancies. We examined the graphs and articles to observe discrepancies with
      text, to observe efficiency of graph presentation, and to determine whether the
      graph portrayed unaggregated data. Results were compared with results from a
      previously published study of graphs from 18 consecutive issues of Annals of
      Emergency Medicine beginning in January 1998. RESULTS: The 12 JAMA issues
      contained 56 research articles, with 64 graphs in the 37 articles that had graphs
      (28 in 27 1999 articles, 36 in 29 2000 articles). Simple bar or point charts
      (63%) predominated. We rarely encountered internal errors (8%), contradictions
      with text (3%), numeric distortion (6%), lack of visual clarity (5%), nonstandard
      graphing conventions (11%), or extraneous decoration (0%). Graphs generally
      defined all symbols (98%), but 31% were not self-explanatory; that is, despite
      knowing the study's design and reading the figure's legend, we could not
      unambiguously interpret the graph. Fourteen percent contained redundancies.
      Graphs infrequently portrayed by-subject data (9%) or advanced features (15%)
      such as pairing, symbolic dimensionality, or small multiples. Forty-eight percent
      (21/44) of graphs did not illustrate the underlying distribution, 48% (26/54) did
      not depict important covariates, and 67% (14/21) did not portray pairing inherent
      in the data. There were no differences between 1999 and 2000 graphs, although we
      noted more graphs in the 2000 issues. Graph quality was similar in Annals of
      Emergency Medicine and JAMA, but graphs were more common in the original research
      articles in JAMA. Although univariate displays predominated in both publications,
      there were more bivariate displays in Annals of Emergency Medicine but fewer
      advanced graphic features. CONCLUSION: The graphs in JAMA were similar to those
      in Annals of Emergency Medicine and, although generally clear and without errors,
      often failed to depict detailed data. Authors and editors could improve data
      presentations by incorporating graphic formats that depict stratified, detailed
      data.

PMID- 12192358
TI  - Effect of structured workshop training on subsequent performance of journal peer
      reviewers.
AB  - STUDY OBJECTIVE: We sought to determine whether peer reviewers who attend a
      formal interactive training session produce better reviews. METHODS: Peer
      reviewers were invited to attend a formal, 4-hour, highly interactive workshop on
      peer review. Attendees received a sample manuscript to read and review in writing
      in advance. The workshop included presentations on analyzing a study and the
      journal's expectations for a quality review, discussion of the sample
      manuscript's flaws and how to address them in a review, discussion of the reviews
      written by the attendees, and discussion of real reviews of other manuscripts
      illustrating key points. The performance of attendees on the basis of standard
      editor quality ratings (1 to 5) was assessed for the 2 years after workshop
      attendance. Control reviewers matched for previous review quality and volume were
      selected from nonattendees of the workshop. In study 1, all average reviewers
      received a standard written invitation. In study 2, 75 randomly selected average
      reviewers were personally and actively recruited with intensive follow-up by
      means of e-mail and telephone calls in an effort to reduce self-selection bias.
      RESULTS: In study 1, 25 reviewers volunteered for the course, were eligible for
      study, attended, and were compared with 25 matched control reviewers. Of
      attendees filling out evaluations, 19% thought it somewhat and 81% thought it
      very helpful. All thought it would improve their subsequent reviews, and 85%
      thought it would improve their review ratings. The mean change in rating after
      the workshop was 0.11 (95% confidence interval [CI] -0.25 to 0.48) for control
      reviewers and 0.10 (95% CI -0.20 to 0.39) for attendees. In study 2, of 75
      reviewers intensively recruited, only 12 (41%) of those who said they would
      attend did. All of the participants thought the workshop would improve their
      performance and ratings. Test scores at the end of the workshop improved in 73%
      of participants compared with scores on pretests. The control reviewers' average
      rating changed by -0.10 (95% CI -0.49 to 0.29) versus 0.06 (95% CI -0.34 to 0.23)
      for attendees. CONCLUSION: Among invited peer reviewers, voluntary attendance at
      a highly structured and interactive workshop was low and did not improve the
      quality of subsequent reviews, contrary to the predictions of attendees. Efforts
      to aggressively recruit average reviewers to a second workshop were time
      consuming, had low success rates, and showed a similar lack of effect on ratings,
      despite improvement in scores on a test instrument. Workshop teaching formats,
      although traditional, are of unproven efficacy.

PMID- 12192359
TI  - The use of dedicated methodology and statistical reviewers for peer review: a
      content analysis of comments to authors made by methodology and regular
      reviewers.
AB  - STUDY OBJECTIVES: In 1997, Annals of Emergency Medicine initiated a protocol by
      which every original research article, in addition to each regular review, was
      concurrently evaluated by 1 of 2 methodology and statistical reviewers. We
      characterized and contrasted comments made by the methodology and regular peer
      reviewers. METHODS: After pilot testing, interrater reliability assessment, and
      revision, we finalized a 99-item taxonomy of reviewer comments organized in 8
      categories. Two authors, uninvolved in the writing of reviews, classified each
      comment from a random sample of methodology reviews from 1999. For 30 of these
      reviews (15 for each methodology reviewer), the 2 authors also scored all (range
      2 to 5) regular reviews. RESULTS: Sixty-five reviews by methodologist A, 60 by
      methodologist B, and 68 by regular reviewers were analyzed. Comments by
      methodologist A most frequently concerned the presentation of results (33% of all
      comments) and methods (17%). Methodologist B commented most frequently on
      presentation of results (28%) and statistical methods (16%). Regular reviewers
      most frequently made non-methodology/statistical comments (45%) and comments on
      presentation of results (18%). Of note, comments made by methodology and regular
      reviewers about methods issues were often contradictory. CONCLUSION: The
      distributions of comments made by the 2 methodology and statistical reviewers
      were similar, although reviewer A emphasized presentation and reviewer B stressed
      statistical issues. The regular reviewers (most of whom were unaware that a
      dedicated methodology and statistical reviewer would be reviewing the article)
      paid much less attention to methodology issues. The 2 dedicated methodology and
      statistical reviewers created reviews that were similarly focused and emphasized
      methodology issues that were distinct from the issues raised by regular
      reviewers.

PMID- 12192360
TI  - The effect of dedicated methodology and statistical review on published
      manuscript quality.
AB  - STUDY OBJECTIVE: We examine how dedicated methodology and statistical review
      affects the quality of manuscripts published in Annals of Emergency Medicine.
      DESIGN: The dedicated reviewers developed a manuscript scoring form based on
      previously used instruments. The form contained 84 unique elements. Eight items
      sought the presence of state-of-the-art features (eg, formal exploration of the
      sensitivity of results to assumptions); the others sought substandard quality.
      Two raters independently scored each original research publication appearing in 4
      consecutive issues of Annals for the presence or absence of each relevant item.
      We then reviewed the formal methodology and statistical review and all subsequent
      correspondence between authors and editors to determine whether the methodology
      and statistical review provided guidance regarding each of the 84 items and
      whether the advice was incorporated into the final manuscript. RESULTS: There
      were 32 original research articles. One was never subjected to methodology and
      statistical review. Reviewers agreed on 94% of all items; single-item agreement
      ranged from 77% to 100%. State-of-the-art features were present in 31 (14%) of
      217 ratings; the methodology and statistical review had commented on 13 (42%) of
      these. State-of-the-art features were absent in 186 (86%) ratings; the
      methodology and statistical review had commented on 33 (18%) of these.
      Substandard features were deemed present in 166 (12%) of 1,519 ratings; the
      methodology and statistical review had commented on 82 (44%) of these.
      Substandard features were absent in 1,333 (88%) ratings; the methodology and
      statistical review had commented on 132 (10%) of these. We found no fatal flaws
      in the published manuscripts. CONCLUSION: Methodology reviewers often failed to
      comment on deficiencies that they had classified as substandard when designing
      this study. Reviews also did not encourage inclusion of state-of-the-art
      abstract, article, and references features. When reviews identified areas in need
      of improvement, only half of the comments led to improved manuscripts. In the
      other half, authors either rebuked the suggestions or the editors did not act
      when suggestions were ignored.

PMID- 12192361
TI  - Emergency medicine continuous certification: why, why now, why me?

PMID- 12192362
TI  - Conflict resolution in emergency medicine.

PMID- 12192363
TI  - Addition of intravenous aminophylline to beta2 -agonist in adults with acute
      asthma.

PMID- 12192364
TI  - Corticosteroid treatment for acute croup.

PMID- 12192366
TI  - Emergency department diagnosis of active labor by lumbosacral spine radiographs.

PMID- 12192367
TI  - The human side of medicine: don't be scared to be personal.

PMID- 12192368
TI  - Stupid payment tricks.

PMID- 12192369
TI  - Utility of ondansetron in children with vomiting.

PMID- 12192370
TI  - Coronary magnetic resonance imaging: current status.

PMID- 12192372
TI  - Leadership at Johannesburg.

PMID- 12192374
TI  - Environmental impact tops list of fears about transgenic animals.

PMID- 12192376
TI  - Comet mission collapses as craft disappears.

PMID- 12192377
TI  - Controversial animal feed builds concrete career in construction.

PMID- 12192378
TI  - Census of marine migration launched to gauge fish stocks.

PMID- 12192379
TI  - Anthrax case provokes doubt among experts.

PMID- 12192381
TI  - Wanted: scientists for sustainability.

PMID- 12192382
TI  - A very brief encounter.

PMID- 12192383
TI  - Summit: vague answers to well-known problems?

PMID- 12192384
TI  - Physicists take issue of misconduct seriously.

PMID- 12192385
TI  - Impartial review is key.

PMID- 12192386
TI  - Fraud: the system works.

PMID- 12192390
TI  - A progression puzzle.

PMID- 12192392
TI  - Lasing on a cloudy afternoon.

PMID- 12192391
TI  - Virus deals anthrax a killer blow.

PMID- 12192393
TI  - Cell evolution: mitochondria in hiding.

PMID- 12192394
TI  - Physical oceanography: inside whitecaps.

PMID- 12192395
TI  - Neurobiology: tuning in by turning off.

PMID- 12192396
TI  - Smog report.

PMID- 12192397
TI  - Conservation biology: openness in management.

PMID- 12192398
TI  - Immunology: a block at the toll gate.

PMID- 12192399
TI  - Rapid renewal of auditory hair bundles.
AB  - Stereocilia, also known as hair bundles, are mechanosensitive organelles of the
      sensory hair cells of the inner ear that can detect displacements on a nanometre
      scale and are supported by a rigid, dense core of actin filaments. Here we show
      that these actin-filament arrays are continuously remodelled by the addition of
      actin monomers to the stereocilium tips, and that the entire core of the
      stereocilium is renewed every 48 hours. This unexpected dynamic feature of
      stereocilia will help our understanding of how auditory sensory function develops
      and is maintained.

PMID- 12192400
TI  - Artificial intelligence: fast hands-free writing by gaze direction.

PMID- 12192401
TI  - Scale dependence of bubble creation mechanisms in breaking waves.
AB  - Breaking ocean waves entrain air bubbles that enhance air-sea gas flux, produce
      aerosols, generate ambient noise and scavenge biological surfactants. The size
      distribution of the entrained bubbles is the most important factor in controlling
      these processes, but little is known about bubble properties and formation
      mechanisms inside whitecaps. We have measured bubble size distributions inside
      breaking waves in the laboratory and in the open ocean, and provide a
      quantitative description of bubble formation mechanisms in the laboratory. We
      find two distinct mechanisms controlling the size distribution, depending on
      bubble size. For bubbles larger than about 1 mm, turbulent fragmentation
      determines bubble size distribution, resulting in a bubble density proportional
      to the bubble radius to the power of -10/3. Smaller bubbles are created by jet
      and drop impact on the wave face, with a -3/2 power-law scaling. The length scale
      separating these processes is the scale where turbulent fragmentation ceases,
      also known as the Hinze scale. Our results will have important implications for
      the study of air-sea gas transfer.

PMID- 12192402
TI  - Directionally selective calcium signals in dendrites of starburst amacrine cells.
AB  - The detection of image motion is fundamental to vision. In many species, unique
      classes of retinal ganglion cells selectively respond to visual stimuli that move
      in specific directions. It is not known which retinal cell first performs the
      neural computations that give rise to directional selectivity in the ganglion
      cell. A prominent candidate has been an interneuron called the 'starburst
      amacrine cell'. Using two-photon optical recordings of intracellular calcium
      concentration, here we find that individual dendritic branches of starburst cells
      act as independent computation modules. Dendritic calcium signals, but not
      somatic membrane voltage, are directionally selective for stimuli that move
      centrifugally from the cell soma. This demonstrates that direction selectivity is
      computed locally in dendritic branches at a stage before ganglion cells.

PMID- 12192403
TI  - A wind origin for Titan's haze structure.
AB  - Titan, the largest moon of Saturn, is the only satellite in the Solar System with
      a dense atmosphere. Titan's atmosphere is mainly nitrogen with a surface pressure
      of 1.5 atmospheres and a temperature of 95 K (ref. 1). A seasonally varying haze,
      which appears to be the main source of heating and cooling that drives
      atmospheric circulation, shrouds the moon. The haze has numerous features that
      have remained unexplained. There are several layers, including a 'polar hood',
      and a pronounced hemispheric asymmetry. The upper atmosphere rotates much faster
      than the surface of the moon, and there is a significant latitudinal temperature
      asymmetry at the equinoxes. Here we describe a numerical simulation of Titan's
      atmosphere, which appears to explain the observed features of the haze. The
      critical new factor in our model is the coupling of haze formation with
      atmospheric dynamics, which includes a component of strong positive feedback
      between the haze and the winds.

PMID- 12192404
TI  - Emergent excitations in a geometrically frustrated magnet.
AB  - Frustrated systems are ubiquitous, and they are interesting because their
      behaviour is difficult to predict; frustration can lead to macroscopic
      degeneracies and qualitatively new states of matter. Magnetic systems offer good
      examples in the form of spin lattices, where all interactions between spins
      cannot be simultaneously satisfied. Here we report how unusual composite spin
      degrees of freedom can emerge from frustrated magnetic interactions in the cubic
      spinel ZnCr(2)O(4). Upon cooling, groups of six spins self-organize into weakly
      interacting antiferromagnetic loops, whose directors -- the unique direction
      along which the spins are aligned, parallel or antiparallel -- govern all low
      temperature dynamics. The experimental evidence comes from a measurement of the
      magnetic form factor by inelastic neutron scattering; the data show that neutrons
      scatter from hexagonal spin clusters rather than individual spins. The hexagon
      directors are, to a first approximation, decoupled from each other, and hence
      their reorientations embody the long-sought local zero energy modes for the
      pyrochlore lattice.

PMID- 12192405
TI  - Chemical investigation of hassium (element 108).
AB  - The periodic table provides a classification of the chemical properties of the
      elements. But for the heaviest elements, the transactinides, this role of the
      periodic table reaches its limits because increasingly strong relativistic
      effects on the valence electron shells can induce deviations from known trends in
      chemical properties. In the case of the first two transactinides, elements 104
      and 105, relativistic effects do indeed influence their chemical properties,
      whereas elements 106 and 107 both behave as expected from their position within
      the periodic table. Here we report the chemical separation and characterization
      of only seven detected atoms of element 108 (hassium, Hs), which were generated
      as isotopes (269)Hs (refs 8, 9) and (270)Hs (ref. 10) in the fusion reaction
      between (26)Mg and (248)Cm. The hassium atoms are immediately oxidized to a
      highly volatile oxide, presumably HsO(4), for which we determine an enthalpy of
      adsorption on our detector surface that is comparable to the adsorption enthalpy
      determined under identical conditions for the osmium oxide OsO(4). These results
      provide evidence that the chemical properties of hassium and its lighter
      homologue osmium are similar, thus confirming that hassium exhibits properties as
      expected from its position in group 8 of the periodic table.

PMID- 12192406
TI  - Mantle compensation of active metamorphic core complexes at Woodlark rift in
      Papua New Guinea.
AB  - In many highly extended rifts on the Earth, tectonic removal of the upper crust
      exhumes mid-crustal rocks, producing metamorphic core complexes. These structures
      allow the upper continental crust to accommodate tens of kilometres of extension,
      but it is not clear how the lower crust and underlying mantle respond. Also,
      despite removal of the upper crust, such core complexes remain both
      topographically high and in isostatic equilibrium. Because many core complexes in
      the western United States are underlain by a flat Moho discontinuity, it has been
      widely assumed that their elevation is supported by flow in the lower crust or by
      magmatic underplating. These processes should decouple upper-crust extension from
      that in the mantle. In contrast, here we present seismic observations of
      metamorphic core complexes of the western Woodlark rift that show the overall
      crust to be thinned beneath regions of greatest surface extension. These core
      complexes are actively being exhumed at a rate of 5-10 km Myr(-1), and the
      thinning of the underlying crust appears to be compensated by mantle rocks of
      anomalously low density, as indicated by low seismic velocities. We conclude
      that, at least in this case, the development of metamorphic core complexes and
      the accommodation of high extension is not purely a crustal phenomenon, but must
      involve mantle extension.

PMID- 12192407
TI  - A mitochondrial remnant in the microsporidian Trachipleistophora hominis.
AB  - Microsporidia are obligate intracellular parasites of several eukaryotes. They
      have a highly complex and unique infection apparatus but otherwise appear
      structurally simple. Microsporidia are thought to lack typical eukaryotic
      organelles, such as mitochondria and peroxisomes. This has been interpreted as
      support for the hypothesis that these peculiar eukaryotes diverged before the
      mitochondrial endosymbiosis, which would make them one of the earliest offshoots
      in eukaryotic evolution. But microsporidial nuclear genes that encode orthologues
      of typical mitochondrial heatshock Hsp70 proteins have been detected, which
      provides evidence for secondary loss of the organelle or endosymbiont. In
      addition, gene trees and more sophisticated phylogenetic analyses have recovered
      microsporidia as the relatives of fungi, rather than as basal eukaryotes. Here we
      show that a highly specific antibody raised against a Trachipleistophora hominis
      Hsp70 protein detects the presence, under light and electron microscopy, of
      numerous tiny ( approximately 50 x 90 nm) organelles with double membranes in
      this human microsporidial parasite. The finding of relictual mitochondria in
      microsporidia provides further evidence of the reluctance of eukaryotes to lose
      the mitochondrial organelle, even when its canonical function of aerobic
      respiration has been apparently lost.

PMID- 12192408
TI  - Molecular evolution of FOXP2, a gene involved in speech and language.
AB  - Language is a uniquely human trait likely to have been a prerequisite for the
      development of human culture. The ability to develop articulate speech relies on
      capabilities, such as fine control of the larynx and mouth, that are absent in
      chimpanzees and other great apes. FOXP2 is the first gene relevant to the human
      ability to develop language. A point mutation in FOXP2 co-segregates with a
      disorder in a family in which half of the members have severe articulation
      difficulties accompanied by linguistic and grammatical impairment. This gene is
      disrupted by translocation in an unrelated individual who has a similar disorder.
      Thus, two functional copies of FOXP2 seem to be required for acquisition of
      normal spoken language. We sequenced the complementary DNAs that encode the FOXP2
      protein in the chimpanzee, gorilla, orang-utan, rhesus macaque and mouse, and
      compared them with the human cDNA. We also investigated intraspecific variation
      of the human FOXP2 gene. Here we show that human FOXP2 contains changes in amino
      acid coding and a pattern of nucleotide polymorphism, which strongly suggest that
      this gene has been the target of selection during recent human evolution.

PMID- 12192409
TI  - A corollary discharge maintains auditory sensitivity during sound production.
AB  - Speaking and singing present the auditory system of the caller with two
      fundamental problems: discriminating between self-generated and external auditory
      signals and preventing desensitization. In humans and many other vertebrates,
      auditory neurons in the brain are inhibited during vocalization but little is
      known about the nature of the inhibition. Here we show, using intracellular
      recordings of auditory neurons in the singing cricket, that presynaptic
      inhibition of auditory afferents and postsynaptic inhibition of an identified
      auditory interneuron occur in phase with the song pattern. Presynaptic and
      postsynaptic inhibition persist in a fictively singing, isolated cricket central
      nervous system and are therefore the result of a corollary discharge from the
      singing motor network. Mimicking inhibition in the interneuron by injecting
      hyperpolarizing current suppresses its spiking response to a 100-dB sound
      pressure level (SPL) acoustic stimulus and maintains its response to subsequent,
      quieter stimuli. Inhibition by the corollary discharge reduces the neural
      response to self-generated sound and protects the cricket's auditory pathway from
      self-induced desensitization.

PMID- 12192410
TI  - Mechanism of magnesium activation of calcium-activated potassium channels.
AB  - Large-conductance (BK type) Ca(2+)-dependent K(+) channels are essential for
      modulating muscle contraction and neuronal activities such as synaptic
      transmission and hearing. BK channels are activated by membrane depolarization
      and intracellular Ca(2+) and Mg(2+) (refs 6-10). The energy provided by voltage,
      Ca(2+) and Mg(2+) binding are additive in activating the channel, suggesting that
      these signals open the activation gate through independent pathways. Here we
      report a molecular investigation of a Mg(2+)-dependent activation mechanism.
      Using a combined site-directed mutagenesis and structural analysis, we
      demonstrate that a structurally new Mg(2+)-binding site in the RCK/Rossman fold
      domain -- an intracellular structural motif that immediately follows the
      activation gate S6 helix -- is responsible for Mg(2+)-dependent activation.
      Mutations that impair or abolish Mg(2+) sensitivity do not affect Ca(2+)
      sensitivity, and vice versa. These results indicate distinct structural pathways
      for Mg(2+)- and Ca(2+)-dependent activation and suggest a possible mechanism for
      the coupling between Mg(2+) binding and channel opening.

PMID- 12192411
TI  - Multiple regulatory sites in large-conductance calcium-activated potassium
      channels.
AB  - Large conductance, Ca(2+)- and voltage-activated K(+) channels (BK) respond to
      two distinct physiological signals -- membrane voltage and cytosolic Ca(2+) (refs
      1, 2). Channel opening is regulated by changes in Ca(2+) concentration spanning
      0.5 micro M to 50 mM (refs 2-5), a range of Ca(2+) sensitivity unusual among
      Ca(2+)-regulated proteins. Although voltage regulation arises from mechanisms
      shared with other voltage-gated channels, the mechanisms of Ca(2+) regulation
      remain largely unknown. One potential Ca(2+)-regulatory site, termed the 'Ca(2+)
      bowl', has been located to the large cytosolic carboxy terminus. Here we show
      that a second region of the C terminus, the RCK domain (regulator of conductance
      for K(+) (ref. 12)), contains residues that define two additional regulatory
      effects of divalent cations. One site, together with the Ca(2+) bowl, accounts
      for all physiological regulation of BK channels by Ca(2+); the other site
      contributes to effects of millimolar divalent cations that may mediate
      physiological regulation by cytosolic Mg(2+) (refs 5, 13). Independent regulation
      by multiple sites explains the large concentration range over which BK channels
      are regulated by Ca(2+). This allows BK channels to serve a variety of
      physiological roles contingent on the Ca(2+) concentration to which the channels
      are exposed.

PMID- 12192412
TI  - A bacteriolytic agent that detects and kills Bacillus anthracis.
AB  - The dormant and durable spore form of Bacillus anthracis is an ideal biological
      weapon of mass destruction. Once inhaled, spores are transported by alveolar
      macrophages to lymph nodes surrounding the lungs, where they germinate;
      subsequent vegetative expansion causes an overwhelming flood of bacteria and
      toxins into the blood, killing up to 99% of untreated victims. Natural and
      genetically engineered antibiotic-resistant bacilli amplify the threat of spores
      being used as weapons, and heighten the need for improved treatments and spore
      detection methods after an intentional release. We exploited the inherent binding
      specificity and lytic action of bacteriophage enzymes called lysins for the rapid
      detection and killing of B. anthracis. Here we show that the PlyG lysin, isolated
      from the gamma phage of B. anthracis, specifically kills B. anthracis isolates
      and other members of the B. anthracis 'cluster' of bacilli in vitro and in vivo.
      Both vegetative cells and germinating spores are susceptible. The lytic
      specificity of PlyG was also exploited as part of a rapid method for the
      identification of B. anthracis. We conclude that PlyG is a tool for the treatment
      and detection of B. anthracis.

PMID- 12192413
TI  - A saponin-detoxifying enzyme mediates suppression of plant defences.
AB  - Plant disease resistance can be conferred by constitutive features such as
      structural barriers or preformed antimicrobial secondary metabolites. Additional
      defence mechanisms are activated in response to pathogen attack and include
      localized cell death (the hypersensitive response). Pathogens use different
      strategies to counter constitutive and induced plant defences, including
      degradation of preformed antimicrobial compounds and the production of molecules
      that suppress induced plant defences. Here we present evidence for a two
      component process in which a fungal pathogen subverts the preformed antimicrobial
      compounds of its host and uses them to interfere with induced defence responses.
      Antimicrobial saponins are first hydrolysed by a fungal saponin-detoxifying
      enzyme. The degradation product of this hydrolysis then suppresses induced
      defence responses by interfering with fundamental signal transduction processes
      leading to disease resistance.

PMID- 12192414
TI  - Patched acts catalytically to suppress the activity of Smoothened.
AB  - Mutations affecting the transmembrane proteins Patched (Ptc) or Smoothened (Smo)
      that trigger ligand-independent activity of the Hedgehog (Hh) signalling pathway
      are associated with human tumours such as basal cell carcinoma (BCC) and
      medulloblastoma. Despite extensive genetic studies demonstrating the importance
      of these receptor components in embryonic patterning and cancer, the mechanism by
      which Ptc regulates Smo is not understood. Here we report that Ptc and Smo are
      not significantly associated within Hh-responsive cells. Furthermore, we show
      that free Ptc (unbound by Hh) acts sub-stoichiometrically to suppress Smo
      activity and thus is critical in specifying the level of pathway activity.
      Patched is a twelve-transmembrane protein with homology to bacterial proton
      driven transmembrane molecular transporters; we demonstrate that the function of
      Ptc is impaired by alterations of residues that are conserved in and required for
      function of these bacterial transporters. These results suggest that the Ptc
      tumour suppressor functions normally as a transmembrane molecular transporter,
      which acts indirectly to inhibit Smo activity, possibly through changes in
      distribution or concentration of a small molecule.

PMID- 12192415
TI  - Dynamics of ATP-dependent chromatin assembly by ACF.
AB  - The assembly of DNA into chromatin is a critical step in the replication and
      repair of the eukaryotic genome. It has been known for nearly 20 years that
      chromatin assembly is an ATP-dependent process. ATP-dependent chromatin-assembly
      factor (ACF) uses the energy of ATP hydrolysis for the deposition of histones
      into periodic nucleosome arrays, and the ISWI subunit of ACF is an ATPase that is
      related to helicases. Here we show that ACF becomes committed to the DNA template
      upon initiation of chromatin assembly. We also observed that ACF assembles
      nucleosomes in localized arrays, rather than randomly distributing them. By using
      a purified ACF-dependent system for chromatin assembly, we found that ACF
      hydrolyses about 2#150;4 molecules of ATP per base pair in the assembly of
      nucleosomes. This level of ATP hydrolysis is similar to that used by DNA
      helicases for the unwinding of DNA. These results suggest that a tracking
      mechanism exists in which ACF assembles chromatin as an ATP-driven DNA
      translocating motor. Moreover, this proposed mechanism for ACF may be relevant to
      the function of other chromatin-remodelling factors that contain ISWI subunits.

PMID- 12192417
TI  - [Operative data of a psychiatric internation unit in a general hospital of health
      public system in Buenos Aires City].
AB  - The epidemiological projections show that the problems of Mental Health were the
      main health challenge during the last decade. This situation is particularly
      worring in our region. The poor operative data in relation to the care of the
      mental disorders prevent the elaboration of plans on the basis of secure data.
      METHODOLOGY: Records of externation were analized during the period between 1994
      1998 in the men Psychiatric Internation Unity in the Psychopatology Service of
      the Hospital Pinero in Buenos Aires, which is part of the public health service
      of the city. RESULTS: an average time of internation of 42.8 days was reported
      (SD 40,3), which was higher than the 11 days reported in institutions of the
      private health services. An increasing proportional diagnosis of Bipolar Disorder
      was reported (chi square corresponding to tendencies P<0.01, lineality P<0.001)
      and a significative decline in the number of diagnosis of Schizophrenia (chi
      square corresponding to tendencies P<0.05; lineality P<0.05). In this way, the
      ratio of the diagnosis of Schizophrenia and Bipolar Disorder changed from 7:1 in
      1994 to 1,7:1 in 1998. CONCLUSIONS: A variation in the diagnostic habits was
      observed, suggesting that affective disorders were underdiagnosticated. This
      tendency was corrected latter. Similar remarks made by other services in the same
      region support this interpretation of the data.

PMID- 12192418
TI  - [High-dose fluoxetine-induced mania. Review and case report].
AB  - We report the case of a 53 year old woman who attempted suicide taking one high
      dose of fluoxetine, developing a manic episode 19 days later. We also make a
      review about antidepressant-induced mania. In patients with mood disorder, the
      frequency of antidepressant-induced mania switch has been estimated to be 3.7 to
      33%, varying across studies that included different diagnoses and different
      antidepressant treatments. Among the used data basis (Medline) there are papers
      reporting fluoxetine-induced mania. All of them include patients receiving
      adequate dose and time fluoxetine treatment. We found no reports of switch
      occurring after one high-dose of fluoxetine. As the impact on the clinical
      management of antidepressant-induced manic switches is quite high, several
      studies have focused on the possible clinical predictors of this phenomenon. By
      the time, is not possible to determine whether a manic episode is due to the
      natural course of bipolar disorder or to the medication. Thus, the phenomenon of
      antidepressant-induced mania should be defined and investigated with controlled
      prospective studies.

PMID- 12192419
TI  - [Psychotropic coadjuvants in pain treatment].
AB  - Conventionally, analgesic treatment is accomplished by three principal drug
      groups, like nonsteroidal anti-inflammatory drugs, opioids, and local
      anesthetics, through different administration routes and modalities. Currently,
      those analgesics are complemented with coadjuvant and coanalgesic drugs,
      particularly the psychotropic drugs, specially in somatic or visceral pain,
      inflammatory, neurophatic or oncologic types. Recently, best understanding of
      pathophysiological scopes relatives to inflammatory processes and neural damage
      in pain, makes possible an optimum and rational employment of those drugs. The
      psychotropic drugs efficacy must be according as pain type, its pathophysiology,
      the clinical status and the opportunity of pain intervention. The pharmacoeconomy
      must not be forgotten.

PMID- 12192420
TI  - [Cytokines and psychiatry].
AB  - This short review address the concept of cytokine and cytokine families, their
      relationship with CNS, cytokine effects on nervous system (namely, sickness
      behavior) and the cellular source of brain cytokines. In addition, it provides
      selected data on the role of cytokines in mental disorders such as depression,
      schizophrenia, Alzheimer's disease and AIDS-related dementia.

PMID- 12192421
TI  - [Hormonal replacement therapy. Benefits and risks].
AB  - A woman lives an average of between 25 to 30 years since the beginning of
      menopause. This period of life is characterized for the appearance of chronic
      diseases. Estrogens are effective in controlling vasomotor symptoms and also over
      the loss of bone mineral density, therefore lowering the risk of fractures in
      about 25-30%. The use of unopposed estrogens (without progesterone) raises 8 to
      10 times the risk of endometrial and 2 to 3 times the risk of deep venous
      thrombosis as well. Until now, no raise was seen in breast cancer in short
      treatments (less than 5 years) especially if they are not opposed with
      progesterone. The recent publication of the surprising data of the trial Women's
      Health Initiative demonstrates a significative but small increase in the risk of
      breast cancer associated with the use of combined estrogen/progestin therapy
      proportional to the duration of the treatment. The reduction of the plasmatic
      levels of low density lipoproteins associated with the use of Hormonal
      Replacement Therapy (HRT), has not been linked to evident cardiovascular
      protection. There is a higher cardiovascular risk with the use of HRT in the
      first year of the treatment. No clear benefit of HRT has been associated to
      treatment of Alzheimer disease, and is still under investigation its role in the
      prevention of the disease. CONCLUSIONS: 1) A careful analysis of advantages and
      risks of HRT must be done before its use. 2) The treatment must be instituted on
      an individual basis and should be discussed with each patient.

PMID- 12192422
TI  - [The Cytocrome P450 as viewed from clinical practice].
AB  - The cytochrome P450 is an enzymatic system involved in the oxidative metabolism
      of a large number of drugs. Most clinically significant pharmacokinetic
      interactions are related to alterations in drug metabolism, in which the
      cytochrome P450 is implicated. The present article describes the structure and
      functioning of this enzymatic system and the mechanisms involved in metabolic
      interactions. Two important aspects related to this complex system are
      underlined: the genetic polymorphism and the influence of the environment in the
      activity of the enzymes. Finally, the importance of the P450 system is analyzed
      from the point of view of clinical practice.

PMID- 12192423
TI  - [Hepatic reactions to psychiatric drugs].
AB  - Hepatic Drug Reactions can be divided in predictable and nonpredictable. The vast
      majority of drugs produce nonpredictable reactions, unless the patient had a
      previous reaction with the same drug. There are two main pathological lesions
      produced by drugs: one is a cholestasis with mild portal inflammation. The other
      is a viral hepatitic like lesion with variable degree of necrosis. Less frequent
      are chronic hepatitis, cirrhosis, esteatosis, peliosis, intrahepatic thrombosis.
      Cholestasis is a benign and reversible lesion. The hepatitic lesion could produce
      an extensive necrosis with mortality between 2-20 per cent. Very often the
      diagnosis of drug reaction is made by exclusion of other etiologies. Patients on
      prolonged treatments with multiple drugs, should be monitored periodically with
      the study of liver enzymes.

PMID- 12192424
TI  - [A few reflections of a clinician on the language of the somatic symptoms].
AB  - This paper presents a series of reflections upon the clinician's activity. His
      duty begins by having to understand what the words uttered by the patient mean
      and by assigning a clinical value to somatic symptoms. While the former of these
      tasks means that the patient must be followed in his particular way of self
      diagnosis of his somatic perceptions and in his particular way of inventing his
      physical reality, the latter is rather easier and it's based on the use of a
      preformed model of the localization, intensity, duration, sequence and normal
      interpretation of the symptoms. The author proposes different metaphors in order
      to understand the abductive method used by clinicians faced with patients'
      demands.

PMID- 12192425
TI  - [Historical evolution of catatonia term].
AB  - The author shows the evolution of catatonia term throughout Medical Science
      History, from the Grecians, French and German High Schools, DSM-IV and ICD-10,
      and its actual position in the Argentine Psychiatry.

PMID- 12192426
TI  - [The ideal functioning of mental health services in the private sector. Ten
      parameters of the evaluation].

PMID- 12192428
TI  - Rulers rule: present and future applications of cerebellar morphometry.

PMID- 12192430
TI  - Reference values for transverse cerebellar diameter throughout gestation.
AB  - The transverse cerebellar diameter (TCD) is well established in the ultrasound
      literature as a reliable parameter for estimating the duration of gestation. In
      cases of growth restriction the cerebellum is usually spared, making TCD a
      reliable indicator of gestational age even when other parameters fall off the
      appropriate growth curve. The purpose of this study is to establish normal values
      for the transverse diameter of the cerebellum in pathology specimens, and to
      determine if these values correlate with those obtained by ultrasound. We
      examined 96 specimens ranging from 14 to 42 weeks gestational age and found that
      our values correlate well with those published in the ultrasound literature. Mean
      TCD with 2 standard deviations for each gestational week were determined as
      reference values.

PMID- 12192431
TI  - Structural analysis of human CCR2b and primate CCR2b by molecular modeling and
      molecular dynamics simulation.
AB  - CCR2b, a chemokine receptor for MCP-1, -2, -3, -4, plays an important role in a
      variety of diseases involving infection, inflammation, and/or injury, as well as
      being a coreceptor for HIV-1 infection. Two models of human CCR2b (hCCR2b) were
      generated by homology modeling and 1 ns restrained molecular dynamics (MD)
      simulation. In one only C113-C190 forms a disulfide bond (SS model); in another
      the potential C32-C277 disulfide bond was formed (2SS model). Analysis of the
      structures and averaged displacements of Calpha atoms of the N-terminal residues
      shows that the main differences between the SS and 2SS models lie in a region
      D25YDYGAPCHKFD36; in the extracellular part of the 2SS model the accessible
      surfaces of N12, F23, Y26, Y28 and F35 are obviously raised and a more stable H
      bond net is formed. The potential energy of the 2SS-water assembly finally
      fluctuated around -43,020 kJ x mol(-1), which is about 302 kJ x mol(-1) lower
      than that of the SS-water assembly. All these results suggest that the 2SS model
      is more favorable. The CCR2b genes of 17 primates were sequenced and four CCR2b
      models for primates Ateles paniscus (A. pan), Hylobates leucogyneus(H. leu),
      Papio cynocephalus (P. cyn) and Trachypithecus francoist ( T. fra) were generated
      based on the 2SS model. A comparison of hCCR2b with primate CCR2b also supports
      the importance of the region D25YDYGAPCHKFD36. Electrostatic potential maps of
      human and primate CCR2b all display the dipolar characteristics of CCR2b with the
      negative pole located in the extracellular part and a strong positive pole in the
      cytoplasmic part. Based on the CCR2b model, we suggest that the main functional
      residues fall in the D25YDYGAPCHKFD36 region, and the negative electrostatic
      feature is a non-specific, but necessary, factor for ligands or gp120/CD4
      binding.

PMID- 12192432
TI  - Isomerism and aromaticity of heterofullerene C70-nPn (n=2-10).
AB  - A systematic investigation on possible structures of heterofullerenes C70-nPn
      (n=2-10) has been performed employing semiempirical MNDO and ab initio methods.
      The stabilities decrease with increasing number of heteroatoms. The structures
      whose carbon atoms are substituted in the para pattern across the equatorial
      hexagons correspond to the most stable isomers. The isomeric pattern of P-doped
      C70 systems follows our previously proposed correlation between the isomerism of
      the fullerene adducts C60Xn/C70Xn and those of the heterofullerenes C60-nNn or
      C60-nBn /C70-nNn or C70-nBn. The aromaticity of the most stable structures of
      heterofullerenes is studied to investigate the heteroatom doping effect on the
      electron delocalization of the fullerene cage.

PMID- 12192433
TI  - [The prevalence of pain in the elderly German population: results of population
      based studies with the Giessen Subjective Complaints List (Giessener
      Beschwerdebogen GBB)].
AB  - METHODS: In a separate population-based cross-sectional study (n = 593; 53,62%
      female) using the short form of the Giessen Subjective Complaints List (Giessener
      Beschwerdebogen GBB-24), data was collected on current pain in various parts of
      the body (limbs, back, neck, head, stomach). RESULTS: Rheumatic pain is most
      frequent in the elderly. At the age of 76 years or older more than 90% are
      affected from this form of pain. Even if the frequency of pain in the highest
      grading is lightly higher for women than for men, there are only few significant
      sex-related effects. Furthermore, there are only few age-related effects beyond
      the age of 60. CONCLUSIONS: The results show that pain is a common problem in the
      elderly.

PMID- 12192434
TI  - [Indicators of structural quality in palliative care for cancer pain patients in
      Lower-Saxony].
AB  - INTRODUCTION: Palliative care in Germany fails to reach established standards. To
      improve this situation the Chamber of Physicians of Lower-Saxony initiated
      SUPPORT in 1995. Prior to interventions structural quality of care was evaluated,
      specifically the rate of availability of opioid-prescription-forms and the
      ability to treat chronic pain (defined as a construct of knowledge, attitudes and
      skills) were examined. METHODS: The survey was carried out using a standardized
      questionnaire mailed to a representative stratified sample of 1200 physicians.
      RESULTS: Out of 865 answering physicians (response rate 72.1%) only 36.9% had
      their own opioid-prescription-forms. Differentiations regarding to specialty,
      working place (clinic vs. private practice) and treatment of cancer pain patients
      during the last three months shows a better result for GPs (84.6%), internists
      (48.6%), gynecologists (51%) and pain specialists (66.7%). Only 33.1% of
      respondents claimed knowledge of the WHO-3-step-analgesic-ladder. Again the
      aforementioned differentiations yield somewhat better results for GPs (49.2%),
      internists (51.5%), gynecologists (34.7%) and pain specialists (55.6%), however
      only two thirds of these physicians were able to identify the correct number of
      steps of the WHO-algorithm. CONCLUSIONS: These results verify an insufficient
      structural quality in palliative care in Lower-Saxony. In the authors' opinion
      effective improvements can only be achieved by implementing a parallel
      strategy:improvement of basic knowledge in pain management with sufficient
      transfer of this knowledge into practice as well as raising the rate of
      availability of opioid-prescription-forms,and, on the other hand, establishing
      local palliative-care-teams with nursing and medical expertise with 24/7 on
      demand availability to optimize palliative care.

PMID- 12192435
TI  - [Development and evaluation of the multidimensional German pain questionnaire].
AB  - The German pain questionnaire (DSF) has been developed and validated by the Task
      force on "Standardization and Economy in Pain Management" of the German Chapter
      of the International Association for the Study of Pain (DGSS). The concept of the
      DSF is based on a bio (medical) - psycho - social pain model. The modular
      approach to pain assessment consists of:demographic data,pain variables (e. g.
      pain sites, temporal characteristics, duration, intensity),pain associated
      symptoms,affective and sensory qualities of pain (adjective list by Geissner,
      SESCopyright ),pain relieving and intensifying factors,previous pain treatment
      procedures,pain-related disability (Pain Disability Index by Tait et
      al.),depression test CES-D (Center for Epidemiological Studies Depression
      Test),comorbid conditions,social factors (educational level, occupation,
      retirement status, compensation and/or litigation status, disability for
      work),health related quality of life (SF-36Copyright ). Practicability and
      content validity were tested in some 3000 patients. Comparison with external
      criteria (e. g. medical and psychiatric-psychological diagnoses, physician
      determined chronicity of pain) proved good content validity and excellent
      reliability of patients statements in the questionnaire. The great majority of
      patients stated that the DSF covered their pain history completely and in an
      orderly fashion. Difficulty to answer the questions was considered low. The
      German pain questionnaire is a reliable and valid instrument for recording the
      multidimensional experience of pain. Data from such questionnaires are
      indispensable for follow-up studies and internal and external quality
      assessments. The DSF can be ordered from the German Society for the Study of Pain
      (www.dgss.org) and is a core instrument of the computer program "quality
      assurance in pain management" (QUAST) of this society.

PMID- 12192436
TI  - [Health-related quality of life in patients with chronic pain].
AB  - AIMS: An empirical comparison of the performance characteristics of 3 generic
      health-related quality of life (HRQL) measures in pain patients. METHODS: The
      Nottingham Health Profile (NHP), the Medical Outcomes Study 36-item Short-Form
      Health Survey (SF-36), and the German Life Satisfaction Scale (FLZ-M) by Henrich
      et al. were simultaneously employed in a multicenter survey measuring the impact
      of pain on quality of life. The HRQL- instruments were incorporated into the
      German Pain Questionnaire (pain variables, CES-D, Pain Disability Index).
      RESULTS: Characteristics of 3294 pain patients of 13 pain facilities are detailed
      in tables 1-3. Six of the 8 SF-36- and 4 of the 6 NHP-scales show satisfactory
      item-total correlations, bottom- and ceiling-effects, and internal consistency.
      FLZ-M reliabilities are satisfactory. The item weighting procedure of the FLZ-M
      proves to be unnecessary. Principle component analyses result in 7 factors for
      the SF-36 and the NHP. Six of the SF-36-factors are fairly homogeneous. The
      heterogeneity of the NHP- factors is marked. Correlations of the HRQL scales with
      depression (CES-D), anxiety (STAI) and physical functioning (FFbH-R-18) are high
      in all related contents. All instruments discriminate well between headache and
      back pain patients, between several pain grades (v. Korff) and the 3 Mainz pain
      chronicity stages. CONCLUSIONS: The SF-36 has satisfactory to good psychometric
      properties in pain patients, the NHP item selection has to be improved. The FLZ-M
      weighting can be eliminated. The shortcomings of the SF-36 can be overcome by
      adding short scales on role functioning and pain (modular approach).

PMID- 12192437
TI  - [Psychic and somatic findings in jaw or facial pain of unclear origin. Comparison
      of patients with severe and mild symptoms].
AB  - BACKGROUND: Both for medical and dental specialists, patients with facial
      arthromyalgia (FAM) and acute or chronic atypical facial pain (AFP) often
      represent a clinical challenge. Only few empirical studies address the possible
      interaction between facial pain and increased psychosocial stress with a thereby
      heightened risk for a chronic course of disease. OBJECTIVE: To evaluate whether
      FAM or AFP - patients initially presenting with high vs. low pain intensity
      differ in somatic, psychosocial and socioeconomic parameters. METHOD: We chose to
      study a population with a primary diagnosis of myofascial pain of the jaw muscles
      or atypical facial pain and excluded patients with disc displacement, acute
      arthritis and severe arthrosis. Within nine months, 124 consecutive patients with
      FAM ( n=108) or AFP ( n=16) were referred to the departments of maxillary
      surgery, dentistry or neurology of two interdisciplinary academic pain centers.
      Using the patients'ratings on a 100 mm visual analogue scale concerning their
      pain intensity, the group was divided in a subgroup initially presenting with low
      (VAS</=5; n=50) and high pain (VAS>5; n=45). Psychometric evaluation was
      conducted with the SCL-90R (general psychopathology), the State-Trait-Anger
      Expression Inventory (STAXI) and a special questionnaire addressing different
      aspects of chronic pain (modified SBAS-IV). All patients were assessed by a
      maxillary surgeon/specialized dentist with the help of a detailed, standardized
      clinical examination (Helkimo-Index). RESULTS: The group of FAM-/AFP - patients
      according to our inclusion-/exclusion - criteria presenting with a high pain
      intensity showed more psychosocial withdrawal ( p=0.013), a worse self-rated
      psychological status ( p=0.033) and a trend towards more somatization ( p=0.093)
      than patients with lower pain intensity. There was no correlation between initial
      pain intensity and somatic parameters of disease as assessed by the standardized
      clinical examination. Low educational status proved to be the best predictor
      (p<0.001) for belonging to the high (extensive) pain group. CONCLUSIONS: These
      data suggest that FAM-/ AFP - patients initially presenting with a high pain
      intensity have an increased risk for psychosocial stress and maladaptive coping
      behaviour. As both variables are empirically validated risk factors for a chronic
      course in pain-related disease, these patients should be of special interest for
      an interdisciplianary therapeutic setting including psychotherapeutic approaches.

PMID- 12192438
TI  - [Medical expertise of chronic pain syndromes by psychotherapists].
AB  - Chronic pain is the most frequent symptom leading to medical expertise in general
      medicine, orthopedics, neurology and psychiatry. Because of the importance of
      psychosocial factors in the onset and the course of chronic pain syndromes a
      basic psychosomatic diagnostic in every medical expertise of chronic pain is
      necessary. In case of hints to relevant psychosocial factors in the onset and the
      process of chronicity of the pain syndrome a psychotherapeutic medical expertise
      for the assessment of the form and the severity of the psychic disorder and
      psychosocial conflicts as causes, consequences or comorbidities of the pain and
      its social consequences is mandatory. Within a structured procedure using
      international diagnostic systems and classifications of severity scores and
      disabilities an reproducible assessment of performance is possible. The
      guidelines of the German psychosomatic and psychotherapeutic scientific societies
      for medical expertising are presented with their relevance to the assessement of
      patients with chronic pain syndromes. Furthermore the authors discuss based on
      their own experiences and the literature some controversial issues between
      medical experts and officials in charge of pension insurance companies.

PMID- 12192439
TI  - [Arachnoid cyst and tension headache: symptom or accidental finding?].
AB  - We report a 34 year old male patient presenting with occipital headache and
      bilateral shoulder and neck pain. Cranial MRT discloses a large arachnoid cyst
      ventral to the medulla oblongata. The cyst displaces the caudal medulla oblongata
      dorsally to an angle of almost 90 degrees without causing myelopathy. Physical
      examination reveals normal neurological findings without any sign of brainstem
      lesions or lesions of the medulla oblongata. Orthopedic evaluation shows mild
      functional abnormalities as expected in tension headache. Multiple
      electrophysiologic investigations such as motor-, somatosensory-, and acoustic
      evoked potentials, masseter and brain stem reflexes, and electromyography of the
      left M. trapezius were performed and reveal normal results. MR-angiography
      discloses displacement of the left vertebral artery to the right without
      stenosis.We discuss the possibility of a causal connection between the cystic
      lesion and the reported symptoms. Considering the findings based on a review of
      the available literature we conclude that the pain syndrome is very likely
      unrelated to the arachnoid cyst. The latter is herewith an accidental finding in
      a patient with tension headache, and underlines the importance of thoroughfull
      clinical examination to avoid unnecessary diagnostic or therapeutic procedures.

PMID- 12192441
TI  - [The important role of neuropeptides in complex regional pain syndrome].

PMID- 12192440
TI  - [Gabapentin as therapy for vulvitis].

PMID- 12192442
TI  - [Dear colleagues].

PMID- 12192444
TI  - Attention and perceptual implicit memory: effects of selective versus divided
      attention and number of visual objects.
AB  - Extant research presents conflicting results on whether manipulations of
      attention during encoding affect perceptual priming. Two suggested mediating
      factors are type of manipulation (selective vs divided) and whether attention is
      manipulated across multiple objects or within a single object. Words printed in
      different colors (Experiment 1) or flanked by colored blocks (Experiment 2) were
      presented at encoding. In the full-attention condition, participants always read
      the word, in the unattended condition they always identified the color, and in
      the divided-attention conditions, participants attended to both word identity and
      color. Perceptual priming was assessed with perceptual identification and
      explicit memory with recognition. Relative to the full-attention condition,
      attending to color always reduced priming. Dividing attention between word
      identity and color, however, only disrupted priming when these attributes were
      presented as multiple objects (Experiment 2) but not when they were dimensions of
      a common object (Experiment 1). On the explicit test, manipulations of attention
      always affected recognition accuracy.

PMID- 12192445
TI  - Automatic integration of non-perceptual action effect features: the case of the
      associative affective Simon effect.
AB  - In the first phase of Experiment 1, participants were instructed to move a
      response key up or down in response to a go signal. One of both responses was
      consistently followed by an aversive stimulus, whereas the other response was
      never followed by the aversive stimulus. In a subsequent test phase, the same
      responses had to be emitted according to the grammatical category (noun or
      adjective) of positive and negative target words. Results showed that the level
      of affective correspondence between the task-irrelevant positive or negative
      connotation of the target and the motivational significance of the effect of the
      correct response influenced performance. The results of Experiment 2 replicated
      those of Experiment 1, using alternating target-response assignment. These
      findings point to the integration of affective action effect feature codes in the
      cognitive representation of actions.

PMID- 12192446
TI  - Social attention orienting integrates visual information from head and body
      orientation.
AB  - Subjects were asked to detect visual, laterally presented reaction signals
      preceded by head-body cue stimuli in a spatial cueing task. A head rotated
      towards the reaction signal combined with a front view of a body resulted in
      shorter reaction times in comparison to the front view of a head and body. In
      contrast, a cue showing the head and body rotated towards the reaction signal did
      not result in such a facilitation in reaction times. The results suggest that the
      brain mechanisms involved in social attention orienting integrate ventrally
      processed visual information from the head and body orientation. A cue signaling
      that the other person, in his or her frame of reference, has an averted attention
      direction shifts the observer's own attention in the same direction.

PMID- 12192447
TI  - The effects of associative and semantic priming in the lexical decision task.
AB  - Four lexical decision experiments were conducted to examine under which
      conditions automatic semantic priming effects can be obtained. Experiments 1 and
      2 analyzed associative/semantic effects at several very short stimulus-onset
      asynchronies (SOAs), whereas Experiments 3 and 4 used a single-presentation
      paradigm at two response-stimulus intervals (RSIs). Experiment 1 tested
      associatively related pairs from three semantic categories (synonyms, antonyms,
      and category coordinates). The results showed reliable associative priming
      effects at all SOAs. In addition, the correlation between associative strength
      and magnitude of priming was significant only at the shortest SOA (66 ms). When
      prime-target pairs were semantically but not associatively related (Experiment
      2), reliable priming effects were obtained at SOAs of 83 ms and longer. Using the
      single-presentation paradigm with a short RSI (200 ms, Experiment 3), the priming
      effect was equal in size for associative + semantic and for semantic-only pairs
      (a 21-ms effect). When the RSI was set much longer (1,750 ms, Experiment 4), only
      the associative + semantic pairs showed a reliable priming effect (23 ms). The
      results are interpreted in the context of models of semantic memory.

PMID- 12192448
TI  - Evidence for effects of phonological correspondence between visible speech and
      written syllables.
AB  - The present study investigated compatibility effects between written and spoken
      syllables. Participants saw the syllables "Ba" or "Da" printed on a speaker's
      mouth that was articulating either /b wedge / or /d wedge /. Participants
      classified either the printed syllable or the mouth movement by pressing a left
      or right key. Responses were faster when mouth movement and letters were
      congruent regardless of imperative stimulus dimension. As the two stimulus
      dimensions (mouth movements and letters) showed dimensional overlap, but did not
      overlap with the response, stimulus-response compatibility was ruled out
      according to some models. It is argued that the compatibility effect was due to
      the competition of phonological codes at a stage preceding response selection.
      Also, the results lend support to the view that Stroop-like tasks are ambiguous
      with regard to the locus of compatibility effects. Stimulus-response and stimulus
      stimulus compatibility may be observed.

PMID- 12192449
TI  - On the limits of anisochrony in pulse attribution.
AB  - Pulse is the subjective experience of isochrony, which is typically elicited by
      series of sensory events with close to isochronous spacing, as is common in music
      and poetry. We measured the amount of anisochrony in a 10-event sequence with 570
      to 630-ms nominal inter-onset intervals (IOI) that corresponded to the threshold
      for pulse attribution. This threshold was 8.6% of the IOI across 28 participants
      with a wide range of musical training, as compared with 3.5% for detection of
      anisochrony in the same kind of sequence. Musical training led to lower
      thresholds for detection of irregularity but had no effect on pulse attribution.
      The relatively larger amount of anisochrony in pulse attribution may reflect the
      limit for predicting and synchronising with future events. We suggest that this
      limit reflects a compromise between tolerance for naturally occurring deviations
      and the need for precision in timing.

PMID- 12192450
TI  - French descriptions of Wundt's laboratory in Leipzig in 1886.
AB  - Translations are provided of extracts from reports by the French-speaking
      scholars Alfred Grafe and Emile Durkheim concerning the instructional procedures
      in place at Wundt's Institute for Experimental Psychology in Leipzig in the
      summer of 1886. It is stressed that reports such as theirs were of importance,
      not only to researchers, but also to teachers and administrators concerned with
      how the new experimental psychology should be taught, especially with respect to
      practical classes.

PMID- 12192452
TI  - Electroretinograms as an indicator of disease activity in birdshot
      retinochoroidopathy.
AB  - PURPOSE: To determine whether electroretinogram results can help predict the
      success in tapering of immunosuppressive medication in patients with birdshot
      retinochoroidopathy. METHODS: Fifteen patients with birdshot retinochoroidopathy
      who had at least three serial electroretinograms (ERG) during the course of their
      disease were included in the study. Charts of patients seen at the Immunology and
      Uveitis Service at the Massachusetts Eye and Ear Infirmary, Boston, Massachusetts
      were retrospectively reviewed. Seven parameters of the ERGs were examined: dim
      scotopic amplitude, bright scotopic amplitude, bright scotopic implicit time,
      single-flash photopic amplitude, single-flash photopic implicit time, 30 Hz
      flicker amplitudes, and 30 Hz flicker implicit times. For each parameter the
      patients were divided into two groups, those with normal and those with abnormal
      responses at the time their immunosuppressive medication taper was initiated. The
      percentage of patients in each group who were able to successfully taper their
      immunosuppressive medication was calculated. A successful taper of medication was
      defined as no recurrence of disease signs or symptoms for at least 1 year after
      the medication was terminated. RESULTS: Abnormalities in the bright scotopic
      response amplitudes and 30 Hz flicker implicit times were associated with
      recurrence of inflammation as immunosuppressive therapy was tapered. CONCLUSION:
      ERG can serve as a useful adjunct in helping determine when to initiate tapering
      of immunosuppressive therapy in patients with birdshot retinochoroidopathy.

PMID- 12192453
TI  - Retinal nerve fiber layer measurements using laser scanning polarimetry in
      different stages of glaucomatous optic nerve damage.
AB  - PURPOSE: To evaluate the diagnostic value of polarimetric measurements of the
      retinal nerve fiber layer (RNFL) thickness in different stages of glaucomatous
      optic nerve damage. METHODS: The study included 92 eyes of 46 controls (age
      41.0+/-13.7 years) and a heterogeneous group of 232 eyes of 135 patients with
      different stages of glaucomatous optic nerve damage (age 54.0+/-10.2 years; 68
      patients with primary open-angle glaucoma, 56 with normal-pressure glaucoma and
      11 patients with secondary glaucoma due to primary dispersion syndrome or
      pseudoexfoliation syndrome). All control subjects and patients underwent complete
      ophthalmological examinations including scanning laser polarimetry of the RNFL
      using the GDx (Laser Diagnostic Technologies, San Diego, Calif.) and 15 degrees
      color stereo optic disc photographs. Only subjects and patients with disc area
      less than 3.4 mm(2) were included in the study. The total glaucoma group were
      divided into four subgroups according to the morphological criteria of the
      neuroretinal rim. RESULTS: The stage of morphological glaucomatous optic nerve
      damage was classified as follows: stage 0: n=92, stage 1: n=103, stage 2: n=65,
      stage 3: n=40, and stage 4: n=19. Differences in mean polarimetric retardation
      between controls and eyes with glaucoma were significant for all parameters
      except the variable symmetry. The most significant differences between controls
      and eyes with glaucomatous optic nerve damage were found with the "number"
      variable assigned by the neural network analysis ( P<0.001). With increasing
      stage of glaucomatous optic nerve damage, separation of the variable "the number"
      increased significantly. At a predetermined specificity of 90% the sensitivity of
      the groups with different stages of morphological glaucomatous optic nerve damage
      increased from 32% for stage 1 to 90% for stage 4. CONCLUSION: Polarimetric
      measurement of the RNFL thickness is significantly associated with morphological
      glaucomatous optic nerve damage. The fast performance, easy handling, and low
      cost of RNFL polarimetry mean that it can be included in the routine examination
      of glaucoma patients. Further study and refinement of this technique are
      indicated to improve its usefulness in both clinical diagnosis and in population
      based case identification.

PMID- 12192454
TI  - Multifocal ERG in multiple evanescent white dot syndrome.
AB  - PURPOSE: To investigate the electrophysiological findings of a multifocal ERG in
      multiple evanescent white dot syndrome (MEWDS). METHODS: Multifocal
      electroretinograms (mf-ERG) were recorded from four patients with MEWDS. The
      stimulus array consisted of 61 hexagons and was presented according to a binary m
      sequence. We analyzed the N1- and P1-wave amplitudes as well as P1 latencies of
      the first-order kernels. Local responses and concentric ring averaged responses
      were compared to 20 age-matched normal subjects. All patients underwent
      fluorescein angiography and indocyanine green angiography. RESULTS: In two
      patients, first-order kernel of N1- and P1-wave amplitudes showed supernormal
      results at the very beginning (day 1 to day 7) of the disease. By 2 weeks later,
      N1- and P1-wave amplitudes had decreased to either normal or subnormal values.
      The two patients who presented 2 weeks after the onset of clinical signs showed
      subnormal or decreased amplitudes. The P1 implicit times were within normal
      limits in all patients. CONCLUSION: Our mf-ERG findings show different results
      during the course of the disease. First-order kernel amplitudes seem to reflect
      early disturbances of the photoreceptors in MEWDS and are therefore useful in
      detecting early stages and following up the disease.

PMID- 12192455
TI  - Three new cases of Alstrom syndrome.
AB  - PURPOSE: To report three further cases of Alstrom syndrome and to present a
      review of the literature. METHODS: Three siblings, two brothers and a sister, are
      described. They had complete ophthalmologic examination with retinography and
      fluoroscein angiography. They also underwent general and metabolic examination
      and genetic study. RESULTS: Alstrom syndrome is a rare autosomal recessive
      disorder characterized by atypical retinal pigmentary degeneration, sensorineural
      hearing loss, obesity, non-insulin-dependent diabetes mellitus, and chronic
      nephropathy. The diagnosis is based on clinical, biologic (hyperglycemia with
      hyperinsulinism), and genetic criteria (autosomal recessive disorder on
      chromosome 2). CONCLUSION: Blindness, hearing loss, complications of diabetes,
      and renal failure confirm the gravity of this syndrome. The prognosis regarding
      survival is correlated with the severity of renal failure.

PMID- 12192456
TI  - Phenotypes of 16 Stargardt macular dystrophy/fundus flavimaculatus patients with
      known ABCA4 mutations and evaluation of genotype-phenotype correlation.
AB  - PURPOSE: To determine the phenotypic variability in patients with compound
      heterozygous or homozygous ABCA4 mutations, and to correlate the phenotypes with
      the functional properties of the altered protein. METHODS: Sixteen patients from
      13 families with signs of Stargardt macular dystrophy/fundus flavimaculatus and
      known mutations on both alleles of the ABCA4 gene (15 compound heterozygous, one
      homozygous) were characterized by clinical examination, fundus autofluorescence,
      psychophysics (color vision, kinetic and two-color dark- and light-adapted static
      threshold perimetry), and electrophysiology (Ganzfeld, multifocal ERG, EOG).
      RESULTS: The homozygous 5917delG mutation resulted in the earliest disease
      manifestation (at 5 years) and a general cone-rod dysfunction, whereas the
      compound heterozygous mother (5917delG, G1961E) exhibited a very mild phenotype.
      Compound heterozygotes for the IVS40+5G-->A and the C1488Y or Y362X mutation
      showed also an early age of onset but only a central dysfunction. The effect of
      the 2588G-->C mutation, the G1961E mutation, and the complex mutation L541P
      A1038V depended on the mutation in the second allele. Genotype-phenotype
      correlation appeared possible in most instances. Psychophysics revealed a
      simultaneous yet not necessarily congruent cone and rod dysfunction. CONCLUSIONS:
      The type and combination of ABCA4 mutations in compound heterozygous patients
      determined were compatible with the severity of the phenotype as to age of onset
      and the functional consequences in the majority of patients. Unexplained
      phenotypic differences indicate the influence of other factors. ABCA4 mutations
      result in cone and rod dysfunction. Different disease durations limit the power
      of presently available genotype-phenotype correlations.

PMID- 12192457
TI  - Long-term functional and topographic results seven years after epikeratophakia
      for keratoconus.
AB  - PURPOSE: To analyze the long-term effect of epikeratophakia (EKP) on corneal
      topography and visual acuity of eyes with keratoconus. METHODS: Retrospective
      study of 36 eyes 7.2 years after EKP. Four eyes underwent penetrating
      keratoplasty (PKP) and were excluded from further evaluation. Best-corrected
      visual acuity (BCVA) values were obtained from 32 eyes, corneal refraction and
      astigmatism from 23 eyes, surface asymmetry index (SAI) and surface regularity
      index (SRI) from 17 consecutive eyes that were operated upon after 1991, when the
      Tomey Topographic Modeling System became available. RESULTS: Only four eyes
      needed PKP. In addition to EKP six eyes had compression sutures and/or relaxing
      incisions, and one eye underwent photorefractive keratectomy. Mean refractive
      power of the cornea decreased from 51.8 to 45.8 and astigmatism from 7.2 to 3.8.
      SAI improved from 3.2 to 0.9 and SRI from 3.7 to 0.9. Mean BCVA was 0.3
      preoperatively and 0.6 upon last follow-up. CONCLUSIONS: EKP was able to render
      PKP unnecessary in 32 of 36 eyes during the entire observation period. It was
      successful in permanently flattening the ectatic cornea and reducing astigmatism
      while restoring a symmetrical and smooth corneal surface. As a result, visual
      acuity improved considerably. In view of the young age of keratoconus patients
      needing surgery, and the fact that the lifetime of full-thickness corneal grafts
      is limited, EKP should be considered a valuable alternative to PKP in contact
      lens-intolerant cases of keratoconus without central scarring.

PMID- 12192458
TI  - Visual latency in the spontaneous Pulfrich effect.
AB  - BACKGROUND: Interocular visual latency differences in patients with traumatic
      optic neuropathy due to midface injury were compared using both measurements of
      the delay from the spontaneous Pulfrich effect and pattern visual evoked
      potentials (VEPs). METHODS: Six patients with a spontaneous Pulfrich effect
      following midfacial injury observed a target which oscillated sinusoidally with
      an elliptical path in the frontal plane. The spontaneous Pulfrich delay was
      calculated from the size of the minor axis of the target ellipse on an XY plotter
      adjusted until the patient judged that no depth (i.e. no ellipse) was seen. Six
      separate pattern-reversal VEPs were recorded monocularly, with an artificial
      pupil, for a 4 cycle/degree grating. The mean P100 peak latency for each eye was
      used to calculate interocular latency differences. For both the Pulfrich effect
      and VEP measures normal subjects were included for comparison. RESULTS: Patients
      had P100 delays ranging from 2.8 to 17.8 ms, whereas Pulfrich delays were much
      shorter, ranging from 0.14 to 1.3 ms. A significant positive correlation was
      found between the two measures of delay, but the magnitude of the interocular
      difference in VEP was much greater than the delay calculated for the spontaneous
      Pulfrich effect. Tints used to correct the spontaneous Pulfrich effect in the
      patients were generally of high transmission (75-85%) and not dense enough to
      provoke an effect in normal observers. CONCLUSION: We have described a technique
      to quantify interocular delay associated with a spontaneous Pulfrich effect in
      patients with midfacial trauma. Interocular delays measured from pattern-reversal
      VEPs are similar in direction and relative severity but are larger in absolute
      terms.

PMID- 12192459
TI  - Statistical modelling of the central 10-degree visual field in short-wavelength
      automated perimetry.
AB  - BACKGROUND: Reports of short-wavelength pathway dysfunction in retinal eye
      disease suggest that short-wavelength automated perimetry may be a useful
      technique for the investigation of central visual function. The aim of this study
      was to adapt existing statistical procedures used for the investigation of 30-2
      short-wavelength automated perimetry to the 10-2 program of the Humphrey Field
      Analyser. METHODS: A four- or six-point linear interpolation procedure was used
      to calculate normal visual field sensitivity for each of the 68 stimulus
      locations of the 10-2 program using empirical normal data from 51 normal subjects
      examined using the 30-2 program. Prediction limits for normality were derived at
      each stimulus location, enabling the calculation of age-corrected global
      perimetric indices and construction of probability maps for diffuse and focal
      visual field loss. The normal database was validated by empirical data from five
      normal subjects, stratified for age. RESULTS: The pointwise distribution of
      normal sensitivity exhibited a Gaussian distribution at the majority of stimulus
      locations. The pointwise coefficient of variation did not vary significantly
      across the visual field. Examples of diabetic pseudophakic patients and a patient
      with age-related macular degeneration are presented to illustrate the
      effectiveness of SWAP at detecting visual field abnormality in the central visual
      field. CONCLUSION: Ten-degree SWAP is able to effectively detect focal visual
      field loss in central retinal eye disease which may precede those found using
      conventional perimetry. SWAP may prove to be an invaluable technique for the
      investigation of central retinal eye disease.

PMID- 12192460
TI  - Testing for glaucoma with frequency-doubling perimetry in normals, ocular
      hypertensives, and glaucoma patients.
AB  - BACKGROUND: The aim of this study was to evaluate the diagnostic usefulness of
      the FDT perimeter protocol (C-20-5) in combination with a database system for
      analysis of single test locations. METHODS: One hundred seventy-three ocular
      hypertensive eyes, 116 "preperimetric" open-angle glaucoma eyes (glaucomatous
      optic disc atrophy, elevated intraocular pressure, no visual field defects in
      standard white-on-white perimetry), 199 "perimetric" open-angle glaucoma eyes
      (glaucomatous optic disc atrophy and visual field defects), and 151 control eyes
      underwent FDT screening and conventional white-on-white perimetry. Four repeated
      measurements were carried out in 15 glaucoma patients at 2-h intervals to judge
      reproducibility of all test locations. The present screening strategy begins
      testing at the normal 5% probability level. If a stimulus is not detected,
      further targets are presented. FDT-Viewfinder and statistics software were used
      for case-wise recalculation of all missed localized probability levels and
      correlation with corresponding test locations using conventional perimetry.
      RESULTS: Analysis of repeated measurements in patients reveals that variation of
      single test points can be considerable. However, the numbers of missed test
      stimuli calculated globally or in quadrants are significantly correlated with
      corresponding Octopus visual field defects (Spearman rank correlation P<0.001).
      Using a predefined specificity of 96% in control eyes, 11% of ocular hypertensive
      eyes, 28.5% of "preperimetric" glaucoma eyes and 86.9% of "perimetric" glaucoma
      eyes have been classified glaucomatous using an overall score and with
      consideration of different cut-off points in right and left eyes. CONCLUSION:
      Point-wise analysis of FDT screening results can be helpful for classification of
      patient groups and consideration of the individual learning curve in repeated
      measurements. The C-20-5 protocol of the FDT perimeter is able to detect a
      considerable proportion of glaucomatous patients.

PMID- 12192461
TI  - A new instrument for the quantification of macular pigment density: first results
      in patients with AMD and healthy subjects.
AB  - BACKGROUND: There is growing evidence that the development of age-related macular
      degeneration (AMD) is related to oxidative damage. This makes macular pigment
      (MP) an interesting target for research, as antioxidative quality is related to
      MP. As studies have shown that MP density (MPD) can be increased by dietary
      supplementation, MP may also offer a therapeutic or preventive approach to AMD.
      METHODS: Using scanning laser techniques, we quantified MPD in healthy subjects
      and patients with dry AMD. We introduce a modified scanning laser ophthalmoscope
      (SLO) which includes several advantages for the use in the clinical routine
      compared to the standard SLO. RESULTS: We examined 10 healthy subjects without
      ocular pathology and 10 patients with dry AMD (geographic atrophy). Eyes of
      patients with AMD had a significantly lower MPD (mean value 0.094+/-0.022 density
      units, DU) than healthy eyes (mean value 0.184+/-0.023 DU). CONCLUSIONS: It is
      possible to quantify MPD using a scanning laser ophthalmoscope in a clinical
      setting. The modified SLO offers several improvements with regard to the special
      requirements of the clinical situation. Using the new instrument, we were able to
      detect differences in MPD between patients with dry AMD and young healthy
      subjects. Further studies are needed to evaluate the reliability and
      reproducibility of the method.

PMID- 12192462
TI  - Sustained release of cis-hydroxyproline in the treatment of experimental
      proliferative vitreoretinopathy in rabbits.
AB  - PURPOSE: To evaluate the efficacy of sustained-release cis-4-hydroxyproline
      (CHP), a proline analog that inhibits collagen secretion, on experimental
      proliferative vitreoretinopathy (PVR) in rabbits. METHODS: To demonstrate the
      sustained release of CHP we developed scleral implants weighing 8.5 mg made of a
      homogeneous mixture of poly( D, L-lactide-co-glycolide) (PLGA) and various doses
      of CHP. The CHP release profiles were evaluated by high-performance liquid
      chromatography in vitro. Scleral implants loaded with 20% and 15% of CHP and made
      from PLGA (copolymer ratios 65/35 and 50/50; mean molecular weights 103,000 and
      93,000, respectively) were used to treat experimental PVR and the efficacy was
      studied. In treated eyes, two PLGA 65/35 implants ( n=7), PLGA 50/50 implants (
      n=6), or a PLGA 65/35 and a PLGA 50/50 implant ( n=9) were inserted at the pars
      plana, followed by PVR induction with autologous fibroblasts. Control eyes (
      n=18) received two implants without CHP. Ocular tissue toxicity was evaluated
      histologically. RESULTS: In vitro release studies demonstrated a triphasic
      release pattern. The PLGA 65/35 and PLGA 50/50 implants released CHP over 4 and 7
      weeks, respectively. The PLGA 65/35 implants decreased the incidence of retinal
      detachment from 89% (in controls) to 57% on day 28. When both PLGA 65/35 and PLGA
      50/50 implants were used, the inhibitory effect was synergistically enhanced (
      p=0.0034), while implantation with only PLGA 50/50 implants had no significant
      effect on PVR. No toxic reactions were observed. CONCLUSION: These results
      suggest that the biodegradable polymeric implants containing CHP represent a
      potential treatment for PVR.

PMID- 12192463
TI  - Plasminogen activator inhibitor-1 mRNA expression in cultured pigmented ciliary
      epithelial cells of the porcine eye.
AB  - BACKGROUND: Plasminogen activator inhibitor-1 (PAI-1) is a main regulator of the
      fibrinolytic system. PAI-1 inhibits tissue plasminogen activator and urokinase
      type plasminogen activator, resulting in reduced plasminogen activity and
      attenuated fibrinolysis and proteolysis. The present study was performed to
      determine the gene expression encoding for PAI-1 in cultured pigmented ciliary
      epithelial cells of the porcine eye and to detect PAI-1 activity in cell culture
      supernatants. METHODS: Total mRNA of respective confluent primary cultures of
      porcine ciliary epithelial cells, porcine liver cells and porcine kidney cells
      was isolated. Reverse transcribed PAI-1 mRNA was measured by real-time polymerase
      chain reaction (TaqMan PCR) with PAI-1 primers and probes deduced from the human
      PAI-1 gene. PAI-1 activity in supernatants of the cell cultures was determined by
      a specific chromogenic test (Coatest PAI). RESULTS: PAI-1 mRNA was localized in
      all samples of primary cultures of porcine pigmented ciliary epithelial cells. As
      a negative control we analyzed total mRNA of porcine kidney cells. PAI-1 mRNA was
      not detectable in these cells. On the other hand, we established PAI-1 mRNA in
      porcine liver cells as a positive control. High levels of PAI-1 activity were
      found in all samples of cell culture supernatants. CONCLUSIONS: Our results
      indicate that PAI-1 is produced and secreted by the porcine ciliary epithelium.
      We suggest that PAI-1 together with components of the fibrin/fibrinolytic system
      may be involved in aqueous humor outflow. Overproduction of PAI-1 may induce less
      fibrinolysis and extracellular proteolysis in aqueous humor and trabecular
      meshwork, which could result in an elevated intraocular pressure by increasing
      the outflow obstruction. Therefore stimulation of PAI-1 production may perhaps
      contribute to the pathogenesis of primary open-angle glaucoma.

PMID- 12192464
TI  - Changes of kynurenic acid content in the rat and chicken retina during ontogeny.
AB  - BACKGROUND: Kynurenic acid (KYNA) is the only known endogenous glutamate receptor
      antagonist and neuroprotectant. After showing the presence of KYNA and its
      synthesising enzymes in the adult rat retina, we examined developmental changes
      of KYNA content in both vascularised rat and avascular chicken retinas. METHODS:
      Retinas from Brown Norway rats and White Leghorn chickens at different
      developmental stages between the embryonic and the adult stages were used. KYNA
      levels were investigated with HPLC. RESULTS: KYNA was present in both rat and
      chicken retinas during ontogeny. The mean (+/- SE) concentration of KYNA found in
      the embryonic rat retina (E20) was 95+/-10 pmol/g wet wt. The KYNA content
      sharply increased within the following 3 days reaching a peak at birth (P0) of
      702+/-77 pmol/g wet wt. At the end of the second postnatal week KYNA content
      decreased to 211+/-29 pmol/g wet wt. A further decrease was observed
      subsequently, with KYNA levels of 100+/-24.6 pmol/g wet wt at 3 month and 58+/-4
      pmol/g wet wt at 12 month. Significant differences in KYNA concentrations between
      the embryonic and post-hatching stages were also observed in the chicken retina.
      In 12-day-old embryonic (E12) retinas the KYNA level was 364+/-48 pmol/g wet wt,
      and in E16 embryos it was 440+/-80 pmol/g wet wt. It significantly decreased to
      200+/-38 pmol/g wet wt at P0 and stayed more or less at this level until P21
      (217.5+/-23.5 pmol/g wet wt). CONCLUSION: KYNA is present in the rat and chicken
      retinas in high concentrations during early developmental stages. This suggests
      that KYNA may play a neuromodulatory role in the retina during development.

PMID- 12192465
TI  - Short-term training increases diagnostic and treatment rate for insomnia in
      general practice.
AB  - OBJECTIVE: To evaluate the effect of short-term training of general practitioners
      (GPs) on their diagnosis and treatment of chronic insomnia. METHODS: A three-step
      randomized control group design was used: After baseline evaluation (T1) a group
      of 9 GPs underwent a training of half a day, while 7 GPs served as a control
      group. The diagnostic and therapeutic handling of insomnia patients was
      reevaluated under obligatory use of a structured diagnostic questionnaire (T2)
      and under optional use of it (T3). RESULTS: From 16 general practices, 4,754
      patients were included. The frequency rate of insomnia was 19.3 %. The lowest
      diagnostic and treatment rate was found for insomnia patients without comorbidity
      (15 % at T1). Systematic non-pharmacological treatment was not offered by the
      GPs. At T2 the diagnosis rate increased significantly from 37.9 % (T1) to 71.5 %
      (T2, p = 0.038). It fell back to lower levels at T3 but remained better than at
      T1. At T3 non-pharmacological treatments and referral to a sleep expert were
      advised more often. CONCLUSION: Short-term training of GPs can significantly
      improve their diagnostic sensitivity and first-line treatment efforts against
      insomnia.

PMID- 12192466
TI  - Intravenous antidepressant treatment: focus on citalopram.
AB  - During the last decade, the number of patients who consult primary care
      physicians or psychiatrists for symptoms of depression has doubled. The majority
      of depressed patients are prescribed oral medication; however, in several
      European countries antidepressant therapy may be initiated with a daily
      intravenous infusion. The choice of intravenous antidepressants was previously
      limited to agents such as dibenzepine, doxepin, clomipramine and viloxazine. More
      recently, the selective serotonin reuptake inhibitor (SSRI) citalopram has been
      administered as an intravenous infusion to severely depressed patients. The
      results from both open and double-blind clinical studies with intravenous
      citalopram suggest that it is an effective and well-tolerated treatment for
      depression. Moreover, when treatment is initiated by infusion and continued
      orally, citalopram is at least as effective as clomipramine, doxepin and
      viloxazine. As with oral treatment, adverse events experienced by patients are
      mild to moderate in severity with 50 % of patients reporting no adverse events.
      The high bioavailability of citalopram indicates that the switch from intravenous
      to oral citalopram would prevent a deterioration of symptoms as plasma drug
      concentrations would be maintained. Thus citalopram, the only SSRI available as
      an intravenous formulation, may be a useful addition for the treatment of
      severely depressed patients who may benefit from more intensive therapy. The aim
      of this paper is to review available data detailing the clinical outcome of
      intravenously administered citalopram in depressed patients.

PMID- 12192467
TI  - Hypocholesterolemia during mixed manic episodes.
AB  - BACKGROUND: An association of relatively low serum cholesterol with both
      depression and suicide has been reported. Depressive symptoms, including
      suicidality, are defining features of mixed mania. Few studies have considered
      differences in cholesterol levels in subjects during mixed bipolar episodes.
      METHODS: Fasting serum cholesterol levels obtained from 174 subjects evaluated
      during mixed and pure manic episodes were compared using ANOVA statistics. Sex
      was included in the analysis and age was used as a covariate. Cholesterol levels
      in the total manic cohort and in the mixed and pure manic subgroups were compared
      with national norms. RESULTS: Fasting serum cholesterol levels were lower in the
      mixed manic subtype compared to the pure manic subtype. As expected, cholesterol
      levels increased with age. No differences were noted between males and females.
      Cholesterol levels were lower in both the mixed and pure manic subtypes when
      compared with national norms. CONCLUSION: Fasting serum cholesterol levels are
      low in manic patients, especially during mixed bipolar episodes. Cholesterol,
      which has been reported to be a negative acute phase reactant, may be lower
      during mixed states as a result of an immune activation.

PMID- 12192468
TI  - Timing of psychoeducational psychotherapeutic interventions in schizophrenic
      patients.
AB  - Psychoeducational interventions for schizophrenic outpatients and their key
      persons have shown impressive long-term effects on the course of illness.
      Psychoeducation is suggested to be offered as early as possible to be most
      effective. This prospective randomized study examines the influence of pre
      therapy duration of illness on the effects of a psychoeducative training. The
      controlled study covered a total of 191 schizophrenic outpatients and comprised
      psychoeducational training and cognitive psychotherapy. Pre-therapy duration of
      illness was divided at 4 and 7 years resulting in groups of short, medium, and
      long duration of psychosis. Study patients were examined for rehospitalization at
      a five year interval. In patients with long duration of illness, attendance at
      psychoeducation did not modify rehospitalization rate. This was true for patients
      with very short duration of psychosis. Only patients with medium duration of
      illness after psychoeducative intervention showed a reduced rehospitalization
      rate. In general, results do recommend psychoeducative intervention at early
      psychosis. However, psychoeducation was not optimally located in patients with a
      very short duration of illness. Psychoeducation showed a most preventive effect
      in patients with a medium duration of illness who already accept their illness
      but are not yet adhering to fatalistic assumptions often established to explain
      the manifestation of illness.

PMID- 12192469
TI  - Reduced grey and white matter volumes in the temporal lobe of male patients with
      chronic schizophrenia.
AB  - Magnetic resonance imaging (MRI) and tissue segmentation were used to quantify
      grey matter, white matter and cerebrospinal fluid (CSF) volumes in the brains of
      32 males with chronic schizophrenia and 32 healthy males. Tissue volumes in the
      frontal, temporal, parietal, and occipital regions were measured separately.
      Males with schizophrenia had significant reductions of grey and white matter
      volumes in the temporal regions compared with controls. Patients also had
      significantly smaller white matter volumes in the cerebrum and increased CSF
      volumes in the frontal and the temporal regions as well as the cerebrum. The
      findings of the present study suggest that volumes of grey and white matter are
      reduced in the temporal region of males with chronic schizophrenia. The volume of
      white matter in the whole brain also appears to be reduced. Among the different
      brains regions, grey matter reduction was significant only in the temporal
      region.

PMID- 12192470
TI  - Periodic limb movements during sleep in alcohol dependent patients.
AB  - Complaints of sleep disturbances are common among alcohol dependent patients
      during subacute abstinence. Recovered patients may show persistent sleep
      abnormalities for months or even years. In the present study we studied the issue
      whether periodic limb movements in sleep and disturbances of nocturnal
      respiration are more frequent in alcohol dependent patients than healthy subjects
      and may be of predictive value for sustained abstinence vs. relapse after
      withdrawal. Forty alcohol dependent patients spent three nights in the sleep
      laboratory at three time points: 2 to 3 weeks after withdrawal (T0) and at follow
      up investigations 6 (T1) and 12 (T2) months after discharge from the hospital.
      Measurements of PLMS-arousal index and nocturnal respiration were performed
      during the first laboratory night of each measurement point. Alcohol dependent
      patients displayed a significantly enhanced PLMS-arousal index at T0 compared to
      age- and gender-matched healthy subjects, whereas no alterations of nocturnal
      respiration were found.The PLMS-arousal index at T0 was significantly elevated in
      patients who relapsed during the next 6 months compared to abstinent patients. In
      a discriminant function analysis the PLMS-arousal index classified 55 % of the
      patients correctly with respect to outcome after 6 months. It correctly predicted
      80 % of abstainers and 44 % of the patients who relapsed. According to
      neurobiological models of the generation of PLMS and the etiopathology of alcohol
      dependence a genetically determined vulnerability of the dopaminergic system is
      discussed as a factor underlying an increased risk of relapse in a subgroup of
      alcohol dependent patients.

PMID- 12192471
TI  - Converging evidence suggests that monoamine neurotransmitter turnover in human
      adults is associated with their season of birth.
AB  - Separate studies on adults, including those in suicidology and another regarding
      personality in the general population, have indicated associations with their
      season of birth. We analyse each of these studies by multiple nonlinear
      regression employing a cosine function for the month of birth, and compare these
      studies regarding the birth months giving the maxima and minima. The method of
      suicide in suicide studies shows a significant month-of-birth variation similar
      to that for the serotonin metabolite 5-HIAA in the separate study on
      cerebrospinal fluid, with a peak around the birth month September and a nadir
      around birth in March. When comparing the personality study with the study on
      cerebrospinal fluid, the trait novelty seeking varies similar to that for the
      dopamine metabolite HVA or the norepinephrine metabolite MHPG, and the trait
      reward dependence varies similar to that for HVA. The trait self-transcendence
      varies similar to the ratio of the dopamine and serotonin metabolites. Dopamine
      turnover in adults thus shows a peak around the birth months November-December,
      and a nadir around the birth months May-June, suggesting a possible involvement
      of the length of photoperiod during their perinatal period. These results provide
      strong evidence for the influence of season of birth on adult monoamine
      neurotransmitter turnover, and give further support for the monoaminergic
      modulation of the temperament and character traits.

PMID- 12192472
TI  - Should mood reactivity be included in the DSM-IV atypical features specifier?
AB  - BACKGROUND: The definition of atypical depression is still an unsolved issue. DSM
      IV atypical features specifier criteria always require mood reactivity, but why
      mood reactivity should be included is unclear. The study aim was to test whether
      mood reactivity should be included in DSM-IV atypical features specifier.
      METHODS: Consecutively, 164 unipolar and 241 "soft" bipolar II major depressive
      episode (MDE) outpatients were interviewed with the Structured Clinical Interview
      for DSM-IV. The DSM-IV criteria for atypical features specifier were strictly
      followed. Associations were tested by univariate logistic regression. RESULTS:
      MDE with atypical features was present in 41.4 % of patients. Bipolar II disorder
      was significantly more common in patients with atypical features. MDE with
      atypical features was significantly associated with bipolar II, female gender,
      lower age of onset, more axis I comorbidity, fewer psychotic features, and more
      depressive mixed states. In the whole sample, mood reactivity was significantly
      associated with all the atypical symptoms, apart from leaden paralysis, and all
      the other atypical symptoms were significantly associated with each other. In the
      bipolar II sub-sample, mood reactivity was associated with many, but not all,
      atypical symptoms, while in the unipolar sub-sample it was associated with no
      atypical symptom. Atypical symptoms were significantly more common in mood
      reactive than in non-mood reactive patients, apart from leaden paralysis. Bipolar
      II disorder and mood reactivity were strongly associated. CONCLUSIONS: Results
      may support the inclusion of mood reactivity in the DSM-IV atypical features
      specifier for bipolar II disorder, but not for unipolar depression.

PMID- 12192473
TI  - Electromyographical differentiation between the acoustic blink and startle
      reflex. Implications for studies investigating startle behavior.
AB  - Recent evidence suggests that electromyographic activity in the orbicularis oculi
      muscle occurring in response to sudden acoustic stimuli consists of two
      overlapping components: the blink and the startle reflex. The aim of the present
      study was to identify these two components in acoustically elicited eyeblink
      responses and to analyze their differential modulation by weak acoustic
      prepulses. The prevalence, latency and amplitude characteristics of double EMG
      peaks in pulse-alone and prepulse-pulse trials (PP) with 30 ms and 100 ms
      interstimulus intervals were assessed in 16 healthy volunteers.EMG responses with
      two peaks were registered in 42.6 % of the pulse-alone trials and in 56.2 % of
      the PP30 and 48.7 % of the PP100 trials, respectively. Prepulse inhibition of the
      amplitude was greater for the second peak (14.2 % (P2) vs. -11.5 % (P1) in PP30
      trials; 62.6 % (P2) vs. 32.3 % (P1) in PP100 trials), resulting also in higher
      P1/P2 amplitude ratios in prepulse-pulse trials (P1/P2: 62.9 % in pulse-alone,
      92.6 % in PP30 and 100.1 % in PP100 trials). In conclusion, double peaks are a
      common phenomenon in human studies of acoustically elicited blink responses. It
      is postulated that the first peak represents the auditory blink reflex, whereas
      the second peak corresponds to the startle reflex, which may be more susceptible
      to prepulse inhibition. This complexity should be taken into account in clinical
      studies of the modulation of the startle reflex.

PMID- 12192474
TI  - Ethics of human stem cells and cloning - a personal view.

PMID- 12192476
TI  - Umbilical cord blood collection in Cesarean section: a comparison before and
      after placental delivery.
AB  - Fetal stem cells transplants depend on nucleated cells from fetal blood. This
      study was a prospective randomized trials to compare the collection of fetal
      blood by gravity into a bag containing anticoagulant, before and after delivery
      of the placenta. The obstetric and the newborn characteristics in the two group
      were not significantly different. The mean volume of fetal blood collected while
      the placental was still in utero was 74.93+/-7.1 ml as against 35.78+/-3.6 ml for
      collection of fetal blood after delivery of the placenta.

PMID- 12192475
TI  - Comparison of ductus venosus blood flow waveform indices of 607 singletons with
      133 multiples at 10-14 weeks gestation. An evaluation in uncomplicated
      pregnancies.
AB  - Abnormal flow profiles in the ductus venosus during early pregnancy may aid in
      diagnosing chromosomopathies, malformations, congenital heart disease, and twin
      twin transfusion syndrome in monochorionic twins. Whereas reference values of
      ductus venosus flow velocities and waveform indices for the late first and early
      second trimester have been reported in singletons, similar reference values for
      multiple pregnancies have not been established in this age group. Therefore, the
      aim of the present ultrasound study in 119 multichorionic and 14 monochorionic
      multiples in human fetuses between 10-14 weeks of gestation was to establish
      reference values for ductus venosus flow waveform indices for multiple
      pregnancies. Data in multiples were compared with those of 607 singletons.
      Analysis of the ductus venosus (DV) flow velocity waveforms consisted of the
      calculation of the pulsatility index (PIV) and peak velocity index (PVIV) for
      veins. Comparing the data of singletons and multichorionic multiples, no
      statistically significant differences were observed between the two groups in any
      of the assessed Doppler parameters. The DV Doppler parameters of the 14
      monochorionic twins that were analysed separately in order to avoid any potential
      bias from preclinical twin-twin transfusion syndrome were also found within the
      normal ranges. In the study population fetal heart rate did neither significantly
      correlate with PIV nor with PVIV. PIV and PVIV decreased from 10 to 14 weeks
      gestation. A 2.9% rate of absent or reverse flow during atrial contraction in
      normal fetuses at 10-14 weeks gestation was found and needs to be taken into
      consideration when this pattern is defined abnormal in screening tests for fetal
      chromosomopathies or congenital heart disease.

PMID- 12192477
TI  - Assessment of a newer technique for cesarean section.
AB  - We present a new method for cesarean section that predominantly employs blunt
      techniques. We used it in 51 patients having a first cesarean section and
      compared the results with 51 matched controls having a standard technique first
      cesarean section.

PMID- 12192478
TI  - Large-core needle biopsy for diagnosis and treatment of breast lesions.
AB  - PURPOSE: Large-core needle biopsy (LCNB) has become a more widely used technique
      in the evaluation of breast lesions. This study was undertaken to access the
      accuracy of percutaneous LCNB on breast lesions and the impact on further
      proceeding. METHODS: A retrospective review of imaging-guided LCNB of 159 breast
      lesions was done. 143 LCNB were taken with ultrasound guided automated spring gun
      biopsy and 16 stereotactic-guided with vacuum-assisted biopsy device. Histology
      and morphobiological parameters were compared with subsequent material from
      surgery. RESULTS: In 113 core biopsies (71%), an infiltrating breast cancer was
      diagnosed, 5 biopsies (3%) yielded in-situ/atypical lesions and a benign lesion
      was shown in 38 cases (24%). In 3 cases, insufficient/necrotic material was
      obtained. 108 patients underwent subsequent surgery. In 100/108 cases (93%),
      histology on LCNB and surgery was identical. LCNB was false negative in 5 core
      biopsies (5%). Immunhistochemical stains of hormone receptors, bcl-2, c-erbB-2,
      p53 and MIB-1 was comparable on LCNB and on surgical material. Based on the
      results of LCNB, 17/113 patients (15%) with infiltrating carcinoma were primarily
      treated with hormones or with neoadjuvant therapy. 32/38 patients (84%) with
      benign lesions were followed up by imaging control. CONCLUSIONS: In patients with
      benign lesions on imaging, open biopsies can be avoided by LCNB. In patients with
      biopsy proven carcinoma, therapy planning is improved. The addition of
      morphobiological parameters allows early individual treatment.

PMID- 12192479
TI  - Prognosis of patients with positive screening but negative diagnostic test for
      gestational diabetes.
AB  - OBJECTIVE: This is a retrospective study that is designed to investigate the
      prognosis of the patients with abnormal diabetes screening test and a negative
      100 g oral glucose tolerance test that is accepted as the diagnostic test for
      gestational diabetes mellitus (GDM). MATERIALS AND METHOD: The records of 281
      pregnant patients were reviewed. The data of the patients divided into groups
      with normal diabetes screening (1 h/50 g oral glucose tolerance test) and
      abnormal diabetes screening. The patients with abnormal diabetes screening were
      further divided into all values normal in 100 g Oral glucose tolerance test
      (OGTT), one value abnormal in 100 g OGTT and GDM subgroups. The prognosis of
      these patients was reanalyzed concerning the complications that may be attributed
      to glucose intolerance. RESULTS: Abnormal diabetes screening test was detected in
      89 patients (31.6%) and 14 cases were diagnosed as GDM (4.9%). The data of 9
      patients were not suitable to analyze. In 31 cases out of 80 (38.75%), an
      obstetric complication was detected. The rate of similar complications was 27.0%
      (52/192) in the control group. The difference in the rate of complications was
      not statistically significant (p>0.05). When the patients with one value abnormal
      in 100 g OGTT, were further evaluated, the complication rates were 3/9 (33.3%)
      for the 1st hour abnormal patients, 1/1 for the 2nd hour abnormal patients and
      1/1 for the 3rd hour abnormal patients. When the values of 100 g OGTT were
      compared in complicated and uncomplicated cases, the difference between the
      groups was not statistically significant (p>0.05). CONCLUSION: 100 g OGTT is the
      universal diagnostic test for GDM. There is a major subgroup of patients whose
      screening positive but diagnostic test (100 g OGTT) negative. These patients seem
      to be prone to develop obstetric complications related to glucose intolerance but
      there is not a proper means to detect these patients in clinical practice.

PMID- 12192480
TI  - Prognostic value of p53 accumulation in epithelial ovarian carcinomas.
AB  - AIM: To evaluate the prognostic significance of p53 expression in epithelial
      ovarian carcinomas (EOC), and to look for correlations between p53 and other
      disease parameters. MATERIAL AND METHODS: Immunohistochemical techniques were
      used to evaluate p53 expression in paraffin-embedded tissue specimens of 50 EOC
      cases. RESULTS: p53 immunoreactivity was present in 33 of the 50 cases (66%). The
      expression of the p53 did not show any association with the tumor histologic
      type, grade or with the disease stage. However, p53 accumulation was
      significantly more prevalent among tumors with high mitotic index ( p<0.01).
      Although median survival was low in the p53 negative cases, this biologic marker
      did not reveal as an independent prognostic factor in Cox's regression analysis.
      CONCLUSION: Abnormalities of p53 expression which is an inducer of apoptosis
      occur commonly in EOC. Although we could not find it as an independent prognostic
      factor, p53 expression should be studied in larger series to reveal its accurate
      prognostic significance.

PMID- 12192481
TI  - Comparison of nitric oxide production and motion characteristics after 3-layer
      percoll and IxaPrep preparation methods of human sperm.
AB  - OBJECTIVE: To compare two different spermatozoa preparation mediums, the three
      layer Percoll (Sigma, St. Louis, MO; salica-based) and the IxaPrep (Medicult,
      Copenhagen, Denmark; non-salica based, polysucrose medium) method, with respect
      to recovery of pregressive motile sperm and various sperm motion characteristics.
      Analysis was determined by computer-aided sperm analysis and nitric oxide (NO)
      production of the supernatant after centrifugation. METHOD: Thirty-nine semen
      specimens were obtained from men who presented for semen analysis and each of
      them was divided into two aliquots for preparation with the two mediums mentioned
      above. The motile sperm recovery, motility percentage and motion parameters were
      measured for each semen specimen (n=39) before and after preparation using one of
      the two above methods. The NO was measured using the chemiluminscence method
      after centrifugation. RESULTS: Recovery rate was higher in the IxaPrep group
      (Ixaprep: 45.4+/-28.7% versus Percoll: 32.3+/-22.7%; p<0.05). The other motion
      characteristics such as average path velocity (VAP) and straight line velocity
      (VSL) were better than those of fresh semen samples [VAP: 72+/-17.2 micro m/s
      (Percoll), 62.8+/-18.2 micro m/s (Ixaprep) vs 52.2+/-9.5 micro m/s (fresh);
      p<0.05; VSL: 51.8+/-13.4 micro m/s (Percoll), 44.8+/-12.9 micro m/s (Ixaprep) vs
      38.6+/-7.9 micro m/s (fresh); p<0.05]. The motility between fresh and post
      preparation semen samples had no significant difference. Hyperactivation of the
      sperm was improved in the IxaPrep group compared with fresh sperm (Percoll:
      24.7+/-16.9% and IxaPrep: 20.5+/-10.5% versus fresh: 9.2+/-9.2%; p<0.05). NO
      produced in the IxaPrep method was significantly lower than that in the Percoll
      method (Ixaprep: 0.24+/-0.3 micro M versus Percoll: 0.54+/-0.91 micro M; p<0.05).
      CONCLUSION: Our data suggests that the IxaPrep method provides a better recovery
      rate, but that other motion characteristics did not demonstrate any significant
      difference. The lower level of NO produced in the IxaPrep preparation method may
      suggest that better sperm quality achieved is due to the decreased NO production.

PMID- 12192482
TI  - Secondary osteoporosis in women. A retrospective analysis.
AB  - Secondary osteoporosis comprises a minority of all osteoporosis cases. In this
      study we summarize the causes of secondary osteoporosis we encountered in
      patients currently on follow-up in our osteoporosis outpatient clinic. A total of
      1015 female patients are involved in the study. Recorded data of the patients are
      evaluated retrospectively. Patients with spine bone mineral density (BMD) 2.5
      standard deviation below a reference range established using our own data
      obtained from a Turkish population of normal healthy women using dual energy X
      ray absorptiometry (T score less than -2.5) were accepted as having osteoporosis.
      We detected osteoporosis in 384 (38%) of the female patients. A secondary cause
      for osteoporosis has been found in 33 (8.6%) of the 384 osteoporotic patients.
      Thyrotoxicosis (n=10), parathyroid adenoma (n=10), and glucocorticoid
      administration (n=7) constituted 82% of the causes of osteoporosis. The data
      obtained in our study indicate that appropriate search for secondary causes of
      osteoporosis is essential because different modalities are needed for treatment.

PMID- 12192483
TI  - Hormone profile of Kuwaiti women with hyperemesis gravidarum.
AB  - OBJECTIVE: To evaluate the incidence of hyperemesis gravidarum among pregnant
      women in Kuwait and the status of HCG, TSH, Total T4 and Free T4 in the serum of
      patients with hyperemesis gravidarum compared with a control group of women.
      METHODOLOGY: During a 6-month period all patients admitted to Maternity Hospital
      with features of hyperemesis gravidarum (excessive vomiting and ketonuria) were
      enlisted into the study. In fifty of these patients and their fifty normal
      controls, the status of serum total (beta)hCG, TSH, total T4 and freeT4 were
      evaluated with AXSYM micro particle enzyme immunoassay. RESULTS: The incidence of
      hyperemesis in the maternity population was 45 per 1000 deliveries. Total
      (beta)hCG and Total T4 and FreeT4 were significantly higher in the hyperemesis
      patients than in the normal controls (p<0.0001, p=0.004 and p=0.01 respectively).
      TSH levels were significantly lower in hyperemesis patients than in their normal
      controls (p<0.0001). There was a strong positive correlation between the total
      (beta)hCG and the gestational age (r=0.8). CONCLUSION: There is a high incidence
      of hyperemesis gravidarum in the Kuwaiti population. Total (beta)hCG, Total T4
      and Free T4 titers were significantly higher in patients with hyperemesis
      gravidarum, but none of the patients showed signs of hyperthyroidism.

PMID- 12192484
TI  - Effect of gonadotropins on human endometrial stromal cell proliferation in vitro.
AB  - It has long been known that endometrial regeneration and proliferation is
      regulated by sex steroids, cytokines and various growth factors. The mechanisms
      responsible for such organized growth are still under investigation. Human
      chorionic gonadotropin/luteinizing hormone (hCG/LH) receptors have been found to
      be localized in human endometrium by immunocytochemistry. Gonadotropins have been
      widely used for hyperstimulation during in vitro fertilization (IVF) procedures;
      however, the direct effect of gonadotropin on the endometrium has not been
      adequately investigated yet. This study attempted to define the effect of
      gonadotropins on the proliferation of human endometrial stromal cells in vitro.
      Human endometrial stromal cells were obtained from hysterectomy specimens and
      cultured in serum-containing media for up to 72 h. The effects of adding 7.5, 15,
      30, 150 mIU/ml of human menopausal gonadotropin (hMG) and follicle stimulating
      hormone (FSH), and 10, 100, 1,000, 10,000 mIU/ml of hCG on cumulative [(3)H]
      thymidine incorporation in endometrial stromal cells were assessed. This study
      demonstrated that FSH and hMG induced significant inhibition in [(3)H]-thymidine
      uptake at all concentrations, respectively (P<0.05). In contrast to the above two
      hormones, hCG exerted inhibitory effect at concentrations of 1,000 and 10,000
      mIU/ml (P<0.05). There was no evidence of dose-response correlations in all three
      gonadotropin experiments. These data imply that gonadotropins at the
      concentrations studied inhibit the proliferation of human endometrial stromal
      cells, at least, in short-term culture in vitro. Accordingly, we cannot negate
      the possibility that administered gonadotropin during ovarian hyperstimulation
      may directly influence the proliferation of human endometrial cells.

PMID- 12192485
TI  - Fetal meconium peritonitis in single and twin pregnancy. Two cases report.
AB  - We present two cases of fetal meconium peritonitis in a single and twin
      pregnancy, respectively. The first case diagnosis was made at 30 weeks and was
      confirmed after delivery of the twins by cesarean section at 37 weeks. The second
      case diagnosis was made at 31 week and was confirmed at 37 weeks. Meconium
      peritonitis is a rare prenatal complication that results from intrauterine
      perforation of small bowel with spillage of sterile meconium into peritoneal
      cavity. We now report two cases of meconium peritonitis diagnosed at 30 and 31
      weeks gestation.

PMID- 12192486
TI  - Simultaneous intrauterine and ovarian pregnancy following treatment with
      clomiphene citrate.
AB  - Heterotopic pregnancy is increasingly being diagnosed since the advent of
      assisted reproductive technology involving the use of superovulatory drugs and/or
      in-vitro fertilization and the availability of high-resolution ultrasound scans.
      There are reports of Heterotopic tubal pregnancies following clomiphene use.
      Heterotopic ovarian pregnancies are however rare. Clomiphene citrate, which is
      widely used in the primary care setting to treat anovulatory infertility, is felt
      safe. We present a case of heterotopic ovarian pregnancy following treatment with
      clomiphene citrate. The diagnosis and management of heterotopic ovarian pregnancy
      are also discussed.

PMID- 12192487
TI  - Co-existent ovarian mucinous cystadenocarcinoma and ovarian choriocarcinoma.
AB  - We present the case of a 63-year-old woman with an ovarian neoplasm in which
      mucinous cystadenocarcinoma and choriocarcinoma coexisted. Blood levels of beta
      hCG were elevated and bilateral ovarian stromal luteinization was seen. The
      rarity of this association and its clinical and pathologic implications are
      discussed.

PMID- 12192488
TI  - Spontaneous prolonged hypertonic uterine contractions (essential uterine
      hypertonus) and a possible infective etiology.
AB  - The management of a pregnant woman presenting with prolonged hypertonic uterine
      contractions (essential uterine hypertonus) and mildly elevated temperature at
      term is described. Histology of the placenta, cord and membranes, following
      delivery, revealed evidence of chorioamnionitis, funisitis and deciduitis. Our
      findings raise the possibility that essential uterine hypertonus may have an
      infective or inflammatory component to its etiology.

PMID- 12192489
TI  - Nickel-induced hypersensitivity: etiology, immune reactions, prevention and
      therapy.
AB  - As a contact allergen causing type I and type IV hypersensitivity, mediated by
      reagins and allergen-specific T lymphocytes, expressed in a wide range of
      cutaneous eruptions following dermal or systemic exposure, nickel has acquired
      the distinction of being among the most frequent causes of hypersensitivity,
      occupationally as well as among the general population. In synoptic form the many
      effects that nickel has on the organism are presented, to provide a comprehensive
      picture of the aspects of that metal with many biologically noxious, but
      metallurgically indispensable characteristics. This paper reviews the
      epidemiology, the prognosis for occupational and non-occupational nickel allergic
      hypersensitivity (NAH), the many types of exposure and the resulting immune
      responses, immunotoxicity and rate of diffusion through the skin. Alternatives
      towards prevention and remediation, topical and systemic, for this pervasive and
      increasing form of morbidity resulting from multiple types of exposure are
      discussed. Merits and limitations of preventive measures in industry and private
      life are considered, as well as the effectiveness of topical and systemic therapy
      in treating NAH.

PMID- 12192491
TI  - Different properties of three isoforms (alpha, beta, and gamma) of transcription
      factor AP-2 in the expression of human keratinocyte genes.
AB  - The transcription factor AP-2/promoter system is essential for gene expression
      associated with ectodermal development, particularly in the neural crest and
      skin. Three AP-2 isoforms, alpha, beta, and gamma, exhibit a highly homologous
      structure, but their functions are considered to be different. Here, we report on
      the role of each AP-2 isoform in complex keratinocyte biology including
      proliferation, differentiation, and carcinogenesis. The expression of AP-2 was
      investigated immunohistochemically in serial skin sections from normal and
      psoriatic skin, and squamous cell carcinoma (SCC). AP-2alpha was present only in
      the nuclei of normal basal keratinocytes, but was significantly increased in
      lesional proliferating keratinocytes of both diseases. AP-2beta was completely
      absent from all skin samples except dermal sweat glands, whereas AP-2gamma was
      present homogeneously throughout the epidermis in normal and psoriatic skin as
      well as in the SCC lesion. Their restricted expression patterns correlated with
      in vitro DNA binding assays using selective keratinocyte gene promoters and three
      recombinant AP-2 isoforms generated bacterially as glutathione S-transferase
      fusion protein. Epidermal growth factor receptor and basal keratin K14 promoters
      bound to AP-2alpha and AP-2gamma with similar affinities, whereas suprabasal
      keratin K1, type I transglutaminase, and involucrin promoters predominantly bound
      to AP-2gamma rather than AP-2alpha. In contrast, AP-2beta did not bind to any of
      the five promoters despite specific binding to the AP-2 consensus probe. These
      results suggest that AP-2alpha is closely associated with keratinocyte
      proliferation and/or carcinogenesis rather than differentiation, while AP-2gamma
      is ubiquitous in all stages of keratinocyte biology. Taken together, three AP-2
      isoforms perform unique roles in the spatial and temporal expression of human
      keratinocyte-related genes, thereby maintaining epidermal homeostasis. Disruption
      of the epidermal AP-2 balance may contribute to hyperproliferative conditions,
      such as psoriasis and SCC.

PMID- 12192490
TI  - Epidermolytic palmoplantar keratoderma of Vorner: re-evaluation of Vorner's
      original family and identification of a novel keratin 9 mutation.
AB  - In 1901, Hans Vorner observed a family with a diffuse non-transgredient
      palmoplantar keratoderma of autosomal dominant inheritance. Histopathologically,
      he found epidermolytic hyperkeratosis as a characteristic sign and diagnostic
      criterion of this disorder. We performed a follow-up study of the family
      originally seen by Vorner in 1901 with clinical, histopathological, and molecular
      investigations. Clinically, affected family members showed the typical diffuse
      keratoses over the entire surface of the palms and soles sharply bordered by red
      margins. A mycotic infection was additionally found in two patients examined.
      Histopathological investigations confirmed epidermolytic hyperkeratosis.
      Molecular studies revealed a novel mutation in keratin 9, N160I, in patients from
      the family. The mutation in the coil-1A domain is thought to have a dominant
      negative effect on the assembly of keratin intermediate filaments, explaining the
      dominant inheritance of the phenotype. These findings give further evidence that
      palmoplantar keratoderma of Vorner represents the same entity as palmoplantar
      keratoderma of Thost, which was recently re-evaluated in Thost's original family
      and shown to be caused by a similar mutation, R162 W, in the same segment of
      keratin 9.

PMID- 12192492
TI  - Bird's eye view observations of the subepidermal nerve network of normal guinea
      pig skin.
AB  - This study was undertaken to visualize the subepidermal nerve networks
      immunohistochemically. Specimens were obtained from the normal skin of the back,
      abdomen and nose of seven adult male Hartley guinea pigs, and immersed in 1 M
      NaCl solution. Dermal sheets were obtained by separating the dermis and
      epidermis, followed by fixation in Zamboni's fixative. The dermal sheets were
      sectioned parallel to the separated surface. Using the immunoperoxidase technique
      and immunofluorescence, the sections were immunostained with primary antibodies
      to S 100 protein (S100), protein gene product 9.5 (PGP 9.5), neuron-specific
      enolase (NSE), substance P (SP) and calcitonin gene-related peptide (CGRP). In
      double-labeled immunofluorescence of PGP 9.5 and SP or CGRP, the sections were
      viewed under a confocal laser scanning microscope. In skin of the back and
      abdomen, networks of S100-, PGP 9.5- and NSE-positive fibers were observed, some
      of which showed a multicentric arrangement. The outermost structures were formed
      by the thickest fibers which were 5-10 micro m thick, the outer networks
      consisted of fibers 3-6 micro m thick, and the inner networks consisted of fibers
      1-3 micro m thick. From these networks, single fibers approximately 0.5 micro m
      thick branched out and terminated in free endings. The SP- and the CGRP-positive
      substances appeared as granules on the PGP 9.5-positive fibers. These results
      confirm that the dermis has a three-layered sensory nerve plexus, i.e. deep,
      superficial and subepidermal. In the skin of the nose, however, nerve networks
      were made up of only thick fibers which were probably situated in the
      subpapillary dermis.

PMID- 12192493
TI  - Association between vitamin D receptor gene polymorphism and psoriasis among the
      Turkish population.

PMID- 12192494
TI  - Mononuclear-macrophages are predominantly classically activated in
      aminopenicillin-induced maculopapular rashes.

PMID- 12192495
TI  - Cerebral hemorrhage in Henoch-Schoenlein syndrome.
AB  - BACKGROUND: Henoch-Schoenlein syndrome (HSS) is the most common form of
      vasculitis seen in childhood. The clinical diagnosis is based on the association
      of nonthrombocytopenic purpura, arthritis and abdominal pain. Nephropathy is the
      most common complication. Hemorrhages can occur in the respiratory,
      gastrointestinal and urinary tracts. Neurological complications are rare, though
      they may be particularly severe. CASE REPORT AND DISCUSSION: Intracranial
      hemorrhage is an extremely rare complication of the disease; we report the case
      of a child with cerebral hemorrhage in HSS and review the literature.

PMID- 12192496
TI  - Extracellular glutamate in the brains of children with severe head injuries: a
      pilot microdialysis study.
AB  - OBJECTIVE: To determine, using a microdialysis technique, the extracellular
      levels of glutamate and non-transmitter amino acids in the brain of children with
      severe head injuries. METHODS: A microdialysis probe was inserted along side the
      intracranial pressure (ICP) bolt in 9 children (age range 2-14 years) with severe
      head injuries (Glasgow coma scale<8). Dialysate samples were collected hourly and
      analysed, using High Performance Liquid Chromatography (HPLC), for glutamate,
      glutamine and various structural amino acids. Clinical monitoring parameters were
      also correlated with amino acid concentrations. CONCLUSIONS: Mean glutamate
      concentrations in the dialysate varied from very low (<5 micro M) to very high
      (>30 micro M). No correlation with outcome at discharge was demonstrated.
      Structural amino acid levels did not follow the glutamate fluctuations. Low
      glutamine/glutamate ratio was associated with increased morbidity, while a high
      ratio was associated with clinical improvement. Glutamate metabolism may have a
      more significant role in the pathophysiology of paediatric head injury than has
      already been recognised.

PMID- 12192497
TI  - Survey of critical care management of severe traumatic head injury in Israel.
AB  - OBJECTIVE: To survey the current monitoring and treatment policies for patients
      with severe traumatic brain injury (STBI) in Israel, and to compare the
      management of pediatric and adult intensive care units (ICUs). DESIGN:
      Questionnaires were sent to the medical directors of all ICUs managing STBI
      patients. RESULTS: All 21 ICUs responded to the questionnaire. All of the units
      were within tertiary hospitals. An intracranial pressure (ICP) monitoring device
      was used in over 75% of the patients in 6 out of7 (86%) of the pediatric
      intensive care units (PICUs), compared with 11 out of 14 (79%) of the adults
      ICUs. Mannitol was used in all of the units for documented elevated ICP. Mild
      hyperventilation (4-4.6 kPa) was applied in 52% of the units. Mild hypothermia
      was routinely used in 4 out of 7 (57%) and hypertonic solutions (NaCI 3%) in 3
      out of 7 (43%) of the PICUs, compared with only 2 out of 14 (14%) and none (0%)
      of the adults ICUs respectively. PICUs aimed for a lower ICP (< or =15 mm Hg) and
      cerebral perfusion pressure (> or =50 mm Hg) than adult ICUs (< or =20 mm Hg and
      > or =60 mmHg respectively). Barbiturates were used only in patients with
      refractory intracranial hypertension. CONCLUSION: This survey reveals a
      relatively high degree of homogeneity in the treatment of STBI patients in
      Israel. Most patients are treated in accordance with recently published
      literature. We attribute this uniformity to the fact that all patients are being
      treated within tertiary care, university-affiliated centers. PICUs are faster at
      implementing new modalities of treatment and tend to adopt more aggressive
      treatment strategies.

PMID- 12192498
TI  - Cytogenetic evaluation of isochromosome 17q in posterior fossa tumors of children
      and correlation with clinical outcome in medulloblastoma. Detection of a novel
      chromosomal abnormality.
AB  - BACKGROUND: A number of chromosomal abnormalities have been described in the
      presence of central nervous system tumors; isochromosome 17q, representing a loss
      of heterozygosity for the short arm of the chromosome 17, is the one most
      frequently reported in association with medulloblastoma. The purpose of this
      study was to evaluate the prognostic correlation of this variable, compared with
      other variables (surgery extent and radiotherapy), with survival. METHODS AND
      RESULTS: We looked for the presence of i(17q) in 32 children affected by
      posterior fossa tumors, including 16 medulloblastomas and 2 teratoid/rhabdoid
      tumors. For our study we used both karyotypic analysis and the fluorescence in
      situ hybridization (FISH) procedure, both on fresh and on paraffin-embedded
      tissues. Cytogenetic analysis allowed us to detect a hitherto unreported
      abnormality in medulloblastoma: ins(1;10)(q31;q23q26). Moreover, 16 of the 32
      patients analyzed by FISH were found to be positive for the presence of i(17q):
      the 2 with teratoid/rhabdoid tumors, 11 of 16 with medulloblastomas, plus 1 with
      ependymoblastoma and 2 with anaplastic astrocytomas. As far as the outcome of
      medulloblastoma patients is concerned, we found that 8 out of the 10 children
      whose tumor had been totally removed had a favorable outcome regardless of the
      presence of i(17q): 4 were i(17q) positive and 4 i(17q) negative. CONCLUSIONS:
      Although it was impossible to draw any definitive conclusion about detection of
      i(17q) in central nervous system tumors in infancy, particularly in the case of
      medulloblastoma, we suggest that this chromosomal abnormality is not an
      independent prognostic factor, but may be a marker for uncontrolled cell
      proliferation.

PMID- 12192499
TI  - Functional anatomy of thalamus and basal ganglia.
AB  - THALAMUS: The human thalamus is a nuclear complex located in the diencephalon and
      comprising of four parts (the hypothalamus, the epythalamus, the ventral
      thalamus, and the dorsal thalamus). The thalamus is a relay centre subserving
      both sensory and motor mechanisms. Thalamic nuclei (50-60 nuclei) project to one
      or a few well-defined cortical areas. Multiple cortical areas receive afferents
      from a single thalamic nucleus and send back information to different thalamic
      nuclei. The corticofugal projection provides positive feedback to the "correct"
      input, while at the same time suppressing irrelevant information. Topographical
      organisation of the thalamic afferents and efferents is contralateral, and the
      lateralisation of the thalamic functions affects both sensory and motoric
      aspects. Symptoms of lesions located in the thalamus are closely related to the
      function of the areas involved. An infarction or haemorrhage thalamic lesion can
      develop somatosensory disturbances and/or central pain in the opposite hemibody,
      analgesic or purely algesic thalamic syndrome characterised by contralateral
      anaesthesia (or hypaesthesia), contralateral weakness, ataxia and, often,
      persistent spontaneous pain. BASAL GANGLIA: Basal ganglia form a major centre in
      the complex extrapyramidal motor system, as opposed to the pyramidal motor system
      (corticobulbar and corticospinal pathways). Basal ganglia are involved in many
      neuronal pathways having emotional, motivational, associative and cognitive
      functions as well. The striatum (caudate nucleus, putamen and nucleus accumbens)
      receive inputs from all cortical areas and, throughout the thalamus, project
      principally to frontal lobe areas (prefrontal, premotor and supplementary motor
      areas) which are concerned with motor planning. These circuits: (i) have an
      important regulatory influence on cortex, providing information for both
      automatic and voluntary motor responses to the pyramidal system; (ii) play a role
      in predicting future events, reinforcing wanted behaviour and suppressing
      unwanted behaviour, and (iii) are involved in shifting attentional sets and in
      both high-order processes of movement initiation and spatial working memory.
      Basal ganglia-thalamo-cortical circuits maintain somatotopic organisation of
      movement-related neurons throughout the circuit. These circuits reveal functional
      subdivisions of the oculomotor, prefrontal and cingulate circuits, which play an
      important role in attention, learning and potentiating behaviour-guiding rules.
      Involvement of the basal ganglia is related to involuntary and stereotyped
      movements or paucity of movements without involvement of voluntary motor
      functions, as in Parkinson's disease, Wilson's disease, progressive supranuclear
      palsy or Huntington's disease. The symptoms differ with the location of the
      lesion. The commonest disturbances in basal ganglia lesions are abulia (apathy
      with loss of initiative and of spontaneous thought and emotional responses) and
      dystonia, which become manifest as behavioural and motor disturbances,
      respectively.

PMID- 12192500
TI  - Thalamic tumors: clinical presentation.
AB  - INTRODUCTION: Thalamic tumors (TTs) account for approximately 1% of all
      intracranial neoplasms. TTs are seen predominantly in children and young adults.
      Most childhood neoplasms in this location are of glial lineage, a large
      proportion being low-grade tumors. The evolution of symptoms before diagnosis is
      characteristically shorter in children than in adults. CLINICAL PRESENTATION:
      Clinical features of TTs reflect the pressure of the mass on the cerebrospinal
      fluid pathways, the pyramidal tracts, the thalamic nuclei and the optic
      radiations. In this paper, we review the clinical data of 20 children with TTs
      seen at our hospital and compare the findings with those in the current
      literature. An acute presentation is not rare and was encountered in 20% of our
      patients, although most individuals had a subacute or slow evolution. Symptoms
      and signs of raised intracranial pressure (65%), motor deficits (40%), and
      seizures (35%), alone or in combination, were the most frequent manifestations of
      TTs. Behavioral and mental changes are not uncommon in TTs and were found in 25%
      of our patients. Involuntary movements (10%) and the classic thalamic syndrome
      (5%) were quite exceptional. Infants and young children with TTs may present with
      macrocephaly, psychomotor delay, and failing vision or disorders of ocular
      movements.

PMID- 12192501
TI  - Basal ganglia and thalamic tumours: an imaging approximation.
AB  - INTRODUCTION: Among brain tumours, those arising from the deep brain are rare. In
      many cases they are low-grade astrocytomas. But primitive neuroectodermal
      tumours, ganglion cell tumours, oligodendrogliomas, lymphomas, and germinal
      neoplasms can also grow up from the basal ganglia and thalamic region. In other
      occasions peripheral neoplasms developing in neighbouring structures like the
      cerebral lobes, the ventricular walls, choroidal plexus, pineal gland and the
      hypothalamic-chiasmatic-suprasellar region can spread to the deep brain. IMAGING:
      Imaging cannot reliably indicate that a histological picture for a tumour of this
      kind should be suspected. Although the macro- and microscopical characteristics
      of brain tumours are often the basis of the imaging findings, these data usually
      overlap and are only useful as an approximation tool. CONCLUSIONS: Nonetheless,
      whilst radiologists and clinicians must always be cautious when evaluating the
      macroscopic peculiarities of a brain tumour, the value of imaging cannot be
      overestimated when any sort of pathology is encountered. Moreover, besides the
      classic CT and MRI findings, new MRI-related techniques, such as magnetic
      resonance spectroscopy (MRS), are able to extract a different kind of information
      from cerebral neoplasms, and they could be important widespread diagnostic
      alternatives in the very near future.

PMID- 12192503
TI  - Bilateral thalamic tumors in children.
AB  - INTRODUCTION: The actual incidence of thalamic tumors is not known, but the
      frequency of the bilateral tumoral involvement of both thalami is even less
      defined. CASE REPORT: In the present paper we report 4 new pediatric cases of
      primary bilateral thalamic tumors (PBTTs) observed in the Pediatric Neurosurgery
      Section at the Catholic University Medical School, Rome. Neuroimaging studies
      could not detect the presence of abnormal neoplastic tissue at the level of the
      midline basal subependymal region of the third ventricle, in the midbrain, and in
      the pineal gland in any of these 4 patients, thus apparently excluding the
      diffusion of a firstly unilateral thalamic tumor to the contralateral thalamus.
      In all of the patients, the lesions appeared as large symmetrical masses on both
      sides of the third ventricle, a feature that seems to further exclude the
      contralateral growth of a previously unilateral tumor. PBTTs appear to remain
      confined to the thalamic nuclei for a long time, and, unlike the unilateral form,
      the border between gray and white matter may not be violated for a relatively
      long time. Unlike in adults, PBTTs do not present with dementia in children.
      Signs and symptoms of increased intracranial pressure (3 cases) and movement
      disorders (tremor, 2 cases) were the presenting clinical manifestations in our 4
      patients. CONCLUSIONS: The diffuse and bilateral involvement of both thalami
      makes surgical therapy barely feasible, even at the present time. Today, the main
      role of surgery is still to obtain a histological diagnosis. Generally, PBTTs are
      low-grade astrocytomas (grade II in the WHO classification), but limited
      anaplastic areas may be found in some patients, so that grade III and IV
      astrocytomas may be expected in a significant proportion of cases.

PMID- 12192502
TI  - Neuroimaging of thalamic tumors in children.
AB  - INTRODUCTION: Thalamic tumors are typical deep brain tumors; their incidence is
      not precisely known because of the different definition criteria. However, taking
      only lesions arising in the thalami into consideration (and excluding those
      secondarily involving the thalami from adjacent structures) approximately 40% of
      thalamic tumors affect patients under 18 years of age and thalamic neoplasms
      account for 2-5% of all intracranial tumors in children. MATERIALS AND METHODS:
      In the present paper we have focused attention on the neuroimaging features of
      thalamic tumors in a pediatric population; based upon personal experience, we
      suggest a rational neuroradiological approach to the diagnostic evaluation,
      describe CT and MRI findings of the most common tumors, and attempt to define
      basic patterns in order to provide the most reliable "pathological" diagnosis.

PMID- 12192504
TI  - Multimodal target point assessment for stereotactic biopsy in children with
      diffuse bithalamic astrocytomas.
AB  - INTRODUCTION: Diffuse glial tumors with bithalamic involvement are rare in
      children. Diagnostic assessment can be difficult as the radiological findings can
      be unspecific. MATERIALS AND METHODS: In order to enhance the diagnostic yield
      metabolic imaging with MRS and PET using FET ( O-(2-[(18)F]fluoroethyl)- L
      tyrosine) was performed in two children (2 and 10 years of age). Co-registered
      images were used for image-guided biopsy, which was planned with neuronavigation
      and stereotaxy simultaneously. RESULTS: Biopsies from the right thalamus were
      planned, but locations were changed in both cases after metabolic imaging was
      available. MRS (thalamic voxel) was typical for a glial tumor in one child. In
      the older girl FET-PET revealed an unexpected lesion in the left cerebellar
      hemisphere, with a tumor-to-cortex ratio of 3.8, as against 1.7 in the thalamus.
      Accordingly, a stereotactic biopsy specimen was taken from the left cerebellar
      hemisphere, and a final diagnosis of anaplastic astrocytoma was made. The other
      patient showed a higher uptake (tumor-to-cortex ratio 1.6) in the left dorsal
      thalamus, compared with bilateral homogeneous hyperintensity of the thalamus
      structures on MRI. Stereotactic biopsy revealed a low-grade diffuse astrocytoma.
      CONCLUSION: Stereotactic biopsy using metabolic imaging and image fusion can
      enhance the diagnostic yield in cases of diffuse pediatric gliomas disclosing
      unexpected 'hot spots'.

PMID- 12192505
TI  - Surgical approach to thalamic tumors.
AB  - INTRODUCTION: Thalamic tumors comprise 1-5% of all brain tumors. Recent
      improvements in therapeutic approaches and surgical techniques have allowed a
      more accurate approach to these lesions and a reduction in morbidity and
      mortality. DISCUSSION: In this article, the various surgical approaches for the
      resection of thalamic tumors are described. Each of these approaches has its own
      indications and risk of complications.

PMID- 12192506
TI  - Presentation of a choroid plexus papilloma mimicking an extradural haematoma
      after a head injury.
AB  - INTRODUCTION: Choroid plexus papillomas are rare, benign tumours of childhood.
      They usually present with subacute symptoms of raised intracranial pressure (ICP)
      commonly due to overproduction of CSF. Less common presentations include focal
      neurological deficits and epilepsy. CASE REPORT: This is the first reported case
      of any intracranial tumour mimicking a traumatic extradural haematoma in
      presentation.

PMID- 12192507
TI  - Variations of lipid and fatty acid contents during the reproductive cycle of the
      anthozoan Renilla koellikeri.
AB  - Lipid and fatty acid contents were monitored in the sea pansy Renilla koellikeri
      during its reproductive cycle. The fluctuations of lipids and fatty acids were
      closely related to sexual development and gonads represented the principal site
      of lipid storage in the colony. Between April and May, fatty acids and lipids
      greatly accumulated just prior to spawning. The subsequent decrease of lipid and
      fatty acid contents in June probably resulted from loss due to spawning. Fatty
      acid composition was assessed for the whole animal and was compared between male
      and female gonads, and between gonads and somatic tissues. Arachidonic acid (AA)
      was the principal fatty acid in the whole colony followed by palmitic acid and
      eicosapentaenoic acid (EPA). The examination of fatty acid variations in gonads
      showed that EPA and AA were highly incorporated in eggs during the month
      preceding spawning, whereas in the same period, EPA was the only fatty acid to
      accumulate in spermatophores. The differences of fatty acid levels observed in
      gonads reflected sex differences observed in colonies. The seasonal variations of
      the omega6/omega3 ratio of the colonies were largely influenced by EPA and AA,
      and appeared as a reliable indicator of the sexual maturity of the sea pansy.

PMID- 12192508
TI  - Characterization of erythrocyte carbonic anhydrase in an ancient fish, the
      longnose gar ( Lepisosteus osseus).
AB  - This study investigates the evolutionary history of vertebrate red blood cell
      carbonic anhydrase (CA) by characterizing the isozyme properties and nucleotide
      sequence of an ancient fish, the longnose gar ( Lepisosteus osseus). The
      inhibitor sensitivities of gar rbc CA closely resembled those for mammalian CA
      II, as well as those for CAs from more recently evolved fishes. The kinetic
      properties of gar rbc CA were not closely aligned with either mammalian CA I and
      CA II, but fit well into an emerging phylogenetic pattern for early vertebrates.
      Gar rbc CA cDNA was also amplified from mRNA using 5' and 3'-RACE and the open
      reading frame consisted of 786 bp. This sequence shares approximately 65%
      identity with the nucleotide and amino acid sequences of both mammalian CA I and
      CA II. When the amino acid sequences within the active site are compared, gar rbc
      CA differs from mammalian CA I, CA II and CA VII by 9, 4 and 3 of the 36 amino
      acids, respectively. Phylogenetic analyses suggest that gar rbc CA diverged
      before the amniotic CAs (CA I, CA II and CA III), but after CA V and CA VII.

PMID- 12192509
TI  - Mechanical efficiency of the trout heart during volume and pressure-loading:
      metabolic implications of the stiffness of the ventricular tissue.
AB  - In the mammalian heart the metabolic costs of pressure loading exceed those of
      volume loading. As evidence suggests that the opposite may be true in fish, we
      evaluated the metabolic costs of volume and pressure loading in the isolated
      trout heart and compared the results with the mammalian heart based on the
      biomechanical properties of cardiac muscle. The highest power output (2.33+/-0.32
      mW g(-1), n=5) appeared at the highest preload pressure tested (0.3 kPa) and at
      an afterload of 5 kPa. At a higher afterload, power did not increase because
      stroke volume fell. The highest mechanical efficiency (20.7+/-2.0%, n=5) was
      obtained at a preload of 0.15 kPa and an afterload of 5 kPa. Further increases in
      preload or afterload did not increase mechanical efficiency, probably because of
      increases in ventricular wall stress which increased the oxygen consumed
      disproportionately more than the stroke work. Under pressure unloading (25%
      decrease in power output), mechanical efficiency was significantly higher in
      comparison with volume unloading. Given that stiffness of the ventricular tissue
      is larger in trout than in rat papillary muscles, it is suggested that the
      increased strain during volume loading is energetically disadvantageous for stiff
      muscles like those of trout, but it is advantageous when muscle stiffness is
      lower as it occurs in the rat papillary muscle.

PMID- 12192510
TI  - Patterns of lipid storage and mobilisation in the female green sea turtle (
      Chelonia mydas).
AB  - Reproductive data from southern Queensland indicate that vitellogenesis in female
      Chelonia mydas takes approximately 8 months and is followed by a migration to a
      breeding area. At Heron Island, females lay multiple clutches over approximately
      3 months. To investigate how females mobilise and store lipid during the breeding
      season we collected plasma, yolk, and fat tissue samples from females at a
      variety of stages during the nesting season. In breeding females, concentrations
      of plasma triglyceride increased seasonally. They reached peak concentrations
      during vitellogenesis and courtship, remained high throughout the nesting season,
      and then declined to a nadir after the last clutch. Plasma protein concentration
      increased throughout the breeding season, peaking following the last clutch for
      the season. Yolk lipids were highest during courtship and were similar throughout
      the nesting season, suggesting that uptake of lipid by ovarian follicles is
      completed prior to the beginning of the nesting season. Plasma triglyceride
      decreases in females with prolonged periods of unsuccessful nesting, and total
      lipid levels in adipose tissue and follicle yolks were significantly lower in
      atretic females. It appears that: (1) endogenous energy reserves can be reduced
      by stochastic environmental events (such as those reducing nesting success), and
      (2) a metabolic shift signalling the end of the nesting season is characterised
      by a drop in plasma triglycerides and slight increase in total plasma protein.

PMID- 12192511
TI  - Electrogenic ion transport in the intestine of the Australian common brushtail
      possum, Trichosurus vulpecula: indications of novel transport patterns in a
      marsupial.
AB  - In this study, electrogenic ion transport in the intestine of the Australian
      common brushtail possum, Trichosurus vulpecula was investigated. In the ileum, a
      Na(+)-dependent, phloridzin- and amiloride-insensitive short-circuit current (
      Isc) was present. Mucosal glucose stimulated a further phloridzin-sensitive, dose
      dependent increase in Isc. A Na(+)-dependent, ouabain-sensitive Isc was also
      present in the caecum and colon. In the proximal and distal colon, amiloride (100
      micro mol l(-1), mucosal) inhibited this Isc by 81+/-4% and 65+/-3%, respectively
      and the Ki for amiloride (approximately 1 micro mol l(-1)) was consistent with
      the inhibition of a classical epithelial Na(+) channel. In the caecum, 50% of the
      Isc was inhibited by amiloride (100 micro mol l(-1), mucosal). The amiloride
      insensitive Isc in the colon was not due to electrogenic Cl(-) secretion, as
      serosal bumetanide (100 micro mol l(-1)) had no effect on the Isc. Furthermore,
      the secretagogues forskolin (10 micro mol l(-1)), carbachol (100 micro mol l(-1))
      and dibutyryl-cAMP or dibutyryl-cGMP (100 micro mol l(-1)) did not stimulate
      electrogenic Cl(-) secretion by the colon. These results indicate that the
      transport properties of the hindgut of the possum differ significantly from those
      of eutherian mammals and may be associated with different functions of the
      hindgut of possums when compared to eutherian mammals.

PMID- 12192512
TI  - Proton pump activity is required for active uptake of chloride in isolated
      amphibian skin exposed to freshwater.
AB  - Net proton secretion and unidirectional chloride fluxes were measured in isolated
      skin of toads ( Bufo bufo) and frogs ( Rana esculenta) mounted in an Ussing
      chamber and exposed to a Ringer's solution on the serosal side and a freshwater
      like solution (1-3 mM Cl(-)) on the external side. Active proton secretion was
      34.2+/-2.0 pmol.cm(-2).s(-1) ( n=18) in frog skin, and 16.7+/-1.7 pmol.cm(-2).s(
      1) ( n=10) in toad skin. Proton secretion by toad skin was dependent on the
      transepithelial potential ( V(T)), and an amiloride-insensitive short-circuit
      current was stimulated by exogenous CO(2)/HCO(3)(-), indicating the presence of a
      rheogenic proton pump. Cl(-) influx was 37.4+/-7.5 pmol.cm(-2).s(-1) ( n=14) in
      frog skin and 19.5+/-3.5 pmol.cm(-2).s(-1) ( n=11) in toad skin. In toad skin,
      the mean Cl(-) flux ratio was larger than expected for simple electro-diffusion.
      In 8 of 11 sets of paired skins, influx was greater than the efflux indicating
      active uptake of Cl(-). Cl(-) influx in toad skin was unaffected by large
      perturbations (100-150 mV) of V(T), which was accomplished by adding amiloride to
      the outer bath under open circuit conditions. A component of the Cl(-) efflux
      seemed to be dependent on V(T). 4,4'-Diisothiocyanato-stilbene-2,2'-disulfonic
      acid (DIDS; 0.3 mM or 1.3 mM) inhibited Cl(-) influx and, surprisingly, increased
      Cl(-) efflux in toad skin. Influx and efflux of Cl(-) in toad skin were highly
      dependent on the external [Cl(-)] in the freshwater range (0.1-4 mM). (36)Cl(-)
      influx decreased whereas the total Cl(-) efflux increased as a function of
      external [Cl(-)]. These data indicate the presence of a DIDS-sensitive,
      electroneutral carrier mechanism with an external binding site for Cl(-).
      Ethoxzolamide (100 micro M), an inhibitor of carbonic anhydrase, reduced proton
      secretion and Cl(-) influx in frog skin. Concanamycin A (0.1-10 micro M), a
      specific vacuolar-type proton pump (V-ATPase) inhibitor, significantly reduced
      proton secretion in frog skin. In addition, concanamycin A (1 micro M)
      significantly reduced Cl(-) influx in frog skin. We suggest that the active
      proton secretion and Cl(-) influx are coupled. We hypothesise that an apical V
      ATPase is capable of energising active Cl(-) uptake in fresh water by creating a
      favourable gradient for an apical HCO(3)(-) exit in exchange for external Cl(-).
      The data also suggest that a carbonic anhydrase activity provides H(+) and
      HCO(3)(-) for apically co-expressed proton pumps and Cl(-)/HCO(3)(-) exchangers.

PMID- 12192513
TI  - Effects of p-chloromercuribenzene sulfonate on water transport across the
      marsupial erythrocyte membrane.
AB  - The effects of exposure of red blood cells (RBC) of three species of marsupial to
      a mercury-containing sulfhydryl-modifying reagent, p-chloromercuribenzene
      sulfonate (PCMBS), on the water diffusional permeability ( P (d)) of their
      membranes were monitored by using an Mn(2+)-doping (1)H nuclear magnetic
      resonance (NMR) technique at 400 MHz. For koala ( Phascolarctos cinereus), RBC
      the maximal inhibition was reached at 37 degrees C in 60 min with 1 mmol.l(-1)
      PCMBS or in 15-30 min with 2 mmol. l(-1) PCMBS. In contrast, in the case of red
      kangaroo ( Macropus rufus) or swamp wallaby ( Wallabia bicolor) RBC, maximal
      inhibition required an incubation of 90 min at 37 degrees C with 2 mmol.l(-1)
      PCMBS. For the RBC of all three species the value of maximal inhibition was very
      high, being 50-70% when measured at 25 degrees C, 60-80% at 30 degrees C and 60
      70% at 37 degrees C. The lowest values of P (d) appeared to be around 2 x 10(-3)
      3 x 10(-3) cm.s(-1) in the temperature range of 25-37 degrees C. The mean value
      of the activation energy of water diffusion ( E (a,d)) was approximately 20-25
      kJ.mol(-1) for control and approximately 40 kJ.mol(-1) for PCMBS-inhibited RBCs.
      These results show that marsupial RBC have a basal permeability to water similar
      to that previously reported for human RBC, but a higher value of the PCMBS
      inhibitable water permeability. This indicates that the higher water permeability
      of marsupial RBC compared with human RBC is associated with a higher fraction of
      protein-mediated water permeability.

PMID- 12192514
TI  - Aldosterone does not regulate amiloride-sensitive Na(+) transport in the colon of
      the Australian common brushtail possum, Trichosurus vulpecula.
AB  - Plasma aldosterone concentrations and the magnitude of amiloride-sensitive Na(+)
      transport in the proximal and distal colon of newly caught wild possums, and of
      possums maintained on either low or high Na(+) diets, were determined to evaluate
      their role in the regulation of salt content of faeces in common brushtail
      possums. Wild animals had a plasma aldosterone concentration of 439+/-115 pmol l(
      1) and high levels of amiloride-sensitive Na(+) transport in both the proximal
      and distal colon. Animals maintained on a low Na(+) diet for 14 days excreted
      very little Na(+) in the urine and had an elevated aldosterone concentration
      (840+/-246 pmol l(-1)), but levels of amiloride-sensitive Na(+) transport in the
      proximal and distal colon were similar to those in wild animals. Conversely,
      while provision of a high Na(+) diet (7 days or 14 days) resulted in increased
      urinary Na(+) excretion and a fall in aldosterone (approximately 250 pmol l(-1)),
      there was no reduction in the amount of amiloride-sensitive Na(+) transport in
      either the proximal or distal colon. These data strongly indicate that
      aldosterone does not regulate amiloride-sensitive Na(+) transport in the colon of
      possums and that the colon is not involved in the regulation of salt content of
      the faeces in this species.

PMID- 12192515
TI  - Cost of flight in the zebra finch ( Taenopygia guttata): a novel approach based
      on elimination of (13)C labelled bicarbonate.
AB  - On three separate occasions, five zebra finches ( Taenopygia guttata) were
      injected intraperitoneally with 0.2 ml 0.29 M NaH(13)CO(3)solution and placed
      immediately into respirometry chambers to explore the link between (13)C
      elimination and both O(2) consumption (VO(2)) and CO(2) production (VCO(2)).
      Isotope elimination was best modelled by a mono-exponential decay. The
      elimination rate (k(c)) of the (13)C isotope in breath was compared to VO(2) (ml
      O(2)/min) and VCO(2) (ml CO(2)/min) over sequential 5-min time intervals
      following administration of the isotope. Elimination rates measured 15-20 min
      after injection gave the closest relationships to VO(2) ( r(2) =0.82) and VCO(2)
      ( r(2)=0.63). Adding the bicarbonate pool size (N(c)) into the prediction did not
      improve the fit. A second group of birds ( n=11) were flown for 2 min (three
      times in ten birds and twice in one) between 15 min and 20 min following an
      injection of 0.2 ml of the same NaH(13)CO(3) solution. Breath samples, collected
      before and after flight, were used to calculate k(c) over the flight period,
      which was converted to VO(2) and VCO(2) using the equation generated in the
      validation experiment for the corresponding time period. The energy expenditure
      (watts) during flight was calculated from these values using the average RQ
      measured during flight of 0.79. The average flight cost measured using the
      bicarbonate technique was 2.24+/-0.11 W (mean+/-SE). This average flight cost did
      not differ significantly from predictions generated by an allometric equation
      formulated by Masman and Klaassen (1987 Auk 104:603-616). It was however
      substantially higher than the predictions based on the aerodynamic model of
      Pennycuick (1989 Oxford University Press), which assumes an efficiency of 0.23
      for flight. The flight efficiency in these birds was 0.11 using this model.
      Flight cost was not related to within-individual variation [general linear model
      (GLM) F(1,31)=1.16, P=0.29] or across-individual variations in body mass (GLM
      F(1,31)=0.26, P=0.61), wingspan (regression F(1,10)=0.01, P=0.94) or wing loading
      (regression F(1, 31)=0.001, P=0.99) in this sample of birds.

PMID- 12192516
TI  - Excitation-contraction coupling in isolated locomotor muscle fibres from the
      pelagic tunicate Doliolum which lack both sarcoplasmic reticulum and transverse
      tubular system.
AB  - In the locomotor muscle of the pelagic tunicate Doliolum, both the sarcoplasmic
      reticulum (SR) and the transverse-tubular (T-tubular) system are absent. The
      mechanism of excitation-contraction (E-C) coupling was studied in single muscle
      fibres enzymatically dissociated from Doliolum denticulatum. Whole cell voltage
      clamp experiments demonstrated an inward ionic current associated with membrane
      depolarisation. This current was blocked by 5 mmol.l(-1)Co(2+), a calcium current
      blocker, and suppressed by nifedipine, a specific L-type calcium channel blocker.
      An increase in the external K(+) concentration to 200 mmol.l(-1) (K(+)
      depolarisation) induced a rise in the intracellular Ca(2+) level detected with
      fluo-3, a Ca(2+)-sensitive dye. However, when 5-10 mmol.l(-1) Co(2+) or 10-15
      micro mol.l(-1) nifedipine was present in the external solution, K(+)
      depolarisation did not induce a rise in the intracellular Ca(2+) level.
      Externally applied 5-10 mmol.l(-1) caffeine or 20 micro mol.l(-1) ryanodine had
      no effect on the intracellular Ca(2+) level. K(+)-depolarisation induced a rise
      in the intracellular Ca(2+) level in the presence of caffeine or ryanodine.
      Replacement of external Na(+) with Li(+) increased intracellular Ca(2+) levels.
      Our results show that contraction of the locomotor muscle in Doliolum is solely
      due to the influx of Ca(2+) through L-type calcium channels, and that relaxation
      is due to extrusion of Ca(2+) by Na(+)/Ca(2+) exchange across the sarcolemma.

PMID- 12192517
TI  - Site-specific forms of antifreeze protein in the beetle Dendroides canadensis.
AB  - It was known previously that overwintering larvae of the beetle Dendroides
      canadensis produce antifreeze proteins (DAFPs) consisting of a family of 12
      similar proteins, and based on sequence variations the DAFPs may be separated
      into three groups. DAFPs were known to be present in hemolymph, midgut fluid and
      in/on epidermal cells located immediately under the cuticle. However, only DAFPs
      1, 2, and 4 were known to be present in the hemolymph, leaving the location of
      the others unknown. In this study, matrix-assisted laser desorption ionization
      time-of-flight (MALDI-TOF) mass spectrometry of hemolymph confirmed the presence
      of DAFPs-1, 2, and 4 (Group I), plus a protein consistent with the mass of DAFP-6
      (Group I). Also, a review of older data revealed the co-purification of DAFP-6
      along with DAFP-4 in hemolymph. However, none of the other DAFPs (Groups II and
      III) were present in hemolymph. In contrast, mass spectrometry of midgut fluid
      demonstrated the absence of DAFPs-1, 2, 4, or 6, however, proteins consistent
      with the masses of all, or a subset of, Groups II and/or III were present.
      Reverse transcriptase polymerase chain reaction (RT-PCR) showed that transcripts
      of all 12 DAFPs were present in the fat body. However, consistent with the MALDI
      TOF data, only Groups II (8, 9, 10, 11) and III (3, 5, 7, 12) transcripts were
      found in midgut epithelia. RT-PCR of epidermal tissue identified dafps- 4, 6, 8
      and 11 (and sometimes 1 and/or 2) as the major transcripts. These data suggest
      that various DAFPs may have evolved to function best in certain sites.

PMID- 12192518
TI  - Analysis of the genome of the moderate halophile Halomonas eurihalina.
AB  - We have studied the genomic organization of Halomonas eurihalina, a moderately
      halophilic bacterium that produces an anionic exopolysaccharide with a
      potentially wide range of applications in industry. To estimate the genome size
      of strain F2-7, large restriction fragments of genomic DNA were separated by
      pulsed-field gel electrophoresis. According to the average size of the resolved
      restriction fragments, the genome size of H. eurihalina strain F2-7 was estimated
      to be around 2500 kb. The physical map of the chromosome for the endonuclease
      SwaI has been constructed. The F2-7 strain has two plasmids, pVE1 and pVE2, and
      in this study we have isolated three new plasmids, pVE3, pVE4, and pVE5, of 5.3,
      16, and 6.5 kb, respectively, from strains H-1, H-217, and H-236 of H.
      eurihalina. We have characterized these plasmids and constructed their physical
      maps. Curing experiments produced no evidence for the involvement of these
      plasmids in the expression of the mucous phenotype.

PMID- 12192519
TI  - Recombinant Rhodococcus sp. strain T09 can desulfurize DBT in the presence of
      inorganic sulfate.
AB  - The putative Rhodococcus rrn promoter region was cloned from the benzothiophene
      desulfurizing Rhodococcus sp. strain T09, and the dibenzothiophene desulfurizing
      gene, dsz, was expressed under the control of the putative rrn promoter in the
      strain T09 using a Rhodococcus-E.coli shuttle vector. Strain T09 harboring the
      expression vector, pNT, could desulfurize dibenzothiophene in the presence of
      inorganic sulfate, methionine, or cysteine, while the Dsz phenotype was
      completely repressed in recombinant cells carrying the gene under the control of
      the native dsz promoter under the same conditions. Among the sulfur sources
      examined, no intermediates were detected and only the final desulfurized product,
      2-hydroxy-biphenyl, was produced using ammonium sulfate as the sulfur source.

PMID- 12192520
TI  - pH-dependent modulation of alkaline phosphatase activity in Serratia marcescens.
AB  - Serratia marcescens is an opportunistic pathogen responsible for causing
      nosocomial infections, corneal ulcer, necrotizing fasciitis, cellulites, and
      brain abscess. Alkaline phosphatase (APase) is believed to play an important role
      in the survival of several intracellular pathogens and their adaptation. We have
      studied the effect of low phosphate concentration and acid pH on the APase
      activities of S. marcescens. In a low phosphate medium, some strains of S.
      marcescens synthesize two different types of APases, a constitutive (CAPase) and
      an inducible (IAPase). Both the CAPase and IAPase isoenzymes completely lost
      their enzyme activities at pH 2.3, within 10 min of incubation at 0 degrees C.
      Acid-treated IAPase isoenzymes I, II, III, and IV solutions when adjusted to pH
      7.8 showed recovery of 70%, 52%, 72%, and 60% of the lost activities,
      respectively. When the pH of the CAPase reaction mixture was raised to pH 7.8,
      the enzyme activity regained only 5% of its initial activity. Variations in
      protein concentration also affected the pH-dependent reversible changes of the
      IAPase activity. The higher the protein concentration, the faster the
      inactivation of enzyme activity observed at acidic pH at 0 degrees C. Conversely,
      the lower the protein concentration, the higher the rate of reactivation of
      enzyme activity observed for IAPase at alkaline pH. Protein interaction studies
      revealed a lack of similarity between CAPase and IAPase, suggesting separate
      genetic origin of these potentially virulent genes of S. marcescens.

PMID- 12192521
TI  - Plant growth-promoting Pseudomonas putida WCS358 produces and secretes four
      cyclic dipeptides: cross-talk with quorum sensing bacterial sensors.
AB  - The most universal cell-cell signaling mechanism in Gram-negative bacteria occurs
      via the production and response to a class of small diffusible molecules called N
      acylhomoserine lactones (AHLs). This communication is called quorum sensing and
      is responsible for the regulation of several physiological processes and many
      virulence factors in pathogenic bacteria. The detection of these molecules has
      been rendered possible by the utilization of genetically engineered bacterial
      biosensors which respond to the presence of exogenously supplied AHLs. In this
      study, using diverse bacterial biosensors, several biosensor activating fractions
      were purified by organic extraction, HPLC and TLC of cell-free culture
      supernatants of plant growth-promoting Pseudomonas putida WCS358. Surprisingly,
      it was observed that the most abundant compounds in these fractions were cyclic
      dipeptides (diketopiperazines, DKPs), a rather novel finding in Gram-negative
      bacteria. The purification, characterization, chemical synthesis of four DKPs are
      reported and their possible role in cell-cell signaling is discussed.

PMID- 12192522
TI  - Wolbachia infections of tephritid fruit flies: molecular evidence for five
      distinct strains in a single host species.
AB  - Endosymbiotic bacteria of the genus Wolbachia are widespread among arthropods and
      can induce cytoplasmic incompatibility, thelytokous parthenogenesis, male-killing
      or feminization in their hosts. Here, we report phylogenetic relationships of
      Wolbachia in tephritid fruit flies based on wsp gene sequences. We also report,
      for the first time, five distinct strains of Wolbachia in Bactrocera ascita sp.
      B. Four of the five Wolbachia strains found in this species were in the same
      groups as those found in other tephritid fruit flies, suggesting possible
      horizontal transmission of Wolbachia from other fruit flies into B. ascita sp. B.
      The unreliability of wsp-specific group primers demonstrated in this study
      suggests that these primers might be useful only for preliminary identification
      of Wolbachia. Final determination of group affiliation needs to be verified with
      wsp sequence data.

PMID- 12192523
TI  - Zinc biosorption from aqueous solution by a halotolerant cyanobacterium
      Aphanothece halophytica.
AB  - We have investigated the characteristics of zinc biosorption by Aphanothece
      halophytica. Zinc could be rapidly taken up from aqueous solution by the cells
      with an equilibrium being reached within 15 min of incubation with 100 mg L(-1)
      ZnCl(2). The adsorbed zinc was desorbed by treatment with 10 mM EDTA. The
      presence of glucose, carbonyl cyanide m-chlorophenylhydrazone (CCCP), and N,N'
      dicyclohexylcarbodiimide (DCCD) did not affect the uptake of zinc. The specific
      uptake of zinc increased at low cell concentration and decreased when cell
      concentration exceeded 0.2 g L(-1). The binding of zinc followed Langmuir
      isotherm kinetics with a maximum zinc binding capacity of 133 mg g(-1) and an
      apparent zinc binding constant of 28 mg L(-1). The presence of an equimolar
      concentration of Mn(2+), Mg(2+), Co(2+), K(+), or Na(+) had no effect on zinc
      biosorption, whereas Ca(2+), Hg(2+), and Pb(2+) showed an inhibitory effect. The
      biosorption of zinc was low at a pH range from 4 to 6, but increased
      progressively at pH 6.5 and 7.

PMID- 12192524
TI  - Conversion of fatty acids by Bacillus sphaericus-like organisms.
AB  - Bacillus sphaericus species are mesophilic round-spored organisms that readily
      utilize fatty acid-based surfactants during growth, but their ability to modify
      fatty acids is unknown. Among 57 B. sphaericus-like strains tested for fatty acid
      transformation activity in Wallen fermentation (WF) medium, ten converted oleic
      acid to a new product determined by gas chromatography - mass spectrometry (GC
      MS) to be 10-ketostearic acid (10-KSA). Additionally, a few other strains
      converted ricinoleic acid and linoleic acid to new products that remain to be
      characterized. Unlike most microbial hydrations of oleic acid, which produce a
      mixture of 10-KSA and 10-hydroxystearic acid, the conversion of oleic acid by B.
      sphaericus strains was unique in that 10-KSA was the sole reaction product. By
      replacing dextrose with sodium pyruvate in WF and adjusting to pH 6.5, conversion
      of oleic acid to 10-KSA by strain NRRL NRS-732 was improved from about 11% to
      more than 60%. Using the defined optimal conditions, the conversion reaction was
      scaled up in a stirred-batch reactor by using technical-grade oleic acid as
      substrate. This is the first report on the characterization of fatty acid
      conversions by B. sphaericus species.

PMID- 12192526
TI  - Growth under alkaline conditions of the salt-tolerant yeast Debaryomyces hansenii
      IFO10939.
AB  - A salt-tolerant yeast Debaryomyces hansenii IFO 10939, which is able to grow at
      pH 10.0, was isolated and characterized. IFO 10939 had the ability of maintaining
      intracellular pH. The in vivo activation of plasma membrane ATPase was observed
      in cells grown at pH 6.2 during conditioning in buffer at pH 9.0. Alkalification
      of growth medium exhibited a significant increase in acetate and propionate
      production. The results suggested that the regulation of intracellular pH was
      involved in plasma membrane ATPase pumping protons out of the cells and weak acid
      formation for the source of the protons in cells growing at high pH.

PMID- 12192525
TI  - Effect of medium composition on the susceptibility of oral streptococci to
      mercuric chloride.
AB  - Although there is considerable interest in identifying mercury-resistant
      bacteria, no standardized assay exists for this purpose. In this study, the
      effect of the composition of the medium on the susceptibility of oral
      streptococci to HgCl(2) was investigated. The minimum inhibitory concentration
      (MIC) of HgCl(2) for 52 streptococcal strains and the reproducibility of MIC
      values for Hg-sensitive and Hg-resistant strains was determined with 11 different
      media. Addition of blood increased the MIC values, and some media (tryptone soya
      agar, with or without blood) could not discriminate between Hg-sensitive and Hg
      resistant strains. The proportion of streptococci that appeared to be resistant
      to Hg was very high (>70%) on some media (mitis-salivarius, tryptone soya,
      Columbia), but not on others (Mueller-Hinton, Brain Heart Infusion,
      Isosensitest). The MICs of the control strains varied considerably on different
      testing occasions for tryptone soya agar (with and without blood), Isosensitest
      agar, and Columbia agar (with blood). Mueller-Hinton (without blood) appeared to
      be the most suitable medium for isolating Hg-resistant oral streptococci.

PMID- 12192527
TI  - Regulation of Escherichia coli formate hydrogenlyase activity by formate at
      alkaline pH.
AB  - Escherichia coli possesses two hydrogenases, Hyd-3 and Hyd-4. These, in
      conjunction with formate dehydrogenase H (Fdh-H), constitute distinct membrane
      associated formate hydrogenlyases, FHL-1 and FHL-2, both catalyzing the
      decomposition of formate to H(2) and CO(2) during fermentative growth. FHL-1 is
      the major pathway at acidic pH whereas FHL-2 is proposed for slightly alkaline
      pH. In this study, regulation of activity of these pathways by formate has been
      investigated. In cells grown under fermentative conditions on glucose in the
      presence of 30 mM formate at pH 7.5, intracellular pH was decreased to 7.1, the
      activity of Fdh-H raised 3.5-fold, and the production of H(2) became mostly Hyd-3
      dependent. These results suggest that at alkaline pH formate increases an
      activity of Fdh-H and of Hyd-3 both but not of Hyd-4.

PMID- 12192528
TI  - Bioremediation of chlorate or perchlorate contaminated water using permeable
      barriers containing vegetable oil.
AB  - A scale model of an in situ permeable barrier, formed by injecting vegetable oil
      onto laboratory soil columns, was used to remove chlorate and perchlorate from
      flowing groundwater. The hypothesis that trapped oil would serve as a substrate
      enabling native microorganisms to reduce chlorate or perchlorate to chloride as
      water flowed through the oil-rich zone had merit. Approximately 96% of the 0.2 mM
      chlorate and 99% of the 0.2 mM perchlorate present in the water was removed as
      water was pumped through columns containing vegetable oil barriers. The product
      formed was chloride. When nitrate at 1.4 mM was added to the water, both nitrate
      and chlorate were removed. High concentrations of chlorate or perchlorate can be
      treated; 24 m M chlorate and 6 mM perchlorate were completely reduced to chloride
      during microcosm incubations. Microorganisms capable of reducing perchlorate are
      plentiful in the environment.

PMID- 12192529
TI  - Activation of the glycosylphosphatidylinositol-anchored membrane proteinase upon
      release from Herpetomonas samuelpessoai by phospholipase C.
AB  - We have analyzed the effects of exogenous phospholipase C (PLC) on the cell
      surface polypeptides and proteinases of Herpetomonas samuelpessoai grown in
      chemically defined conditions by SDS-PAGE gels. Live parasites treated with PLC
      released into the extracellular medium a complex profile of
      glycosylphosphatidylinositol (GPI)-anchored polypeptides ranging from 15 to 100
      kDa, some of them with proteolytic activity. Two major metalloproteinases with
      apparent molecular masses of 63 and 115 kDa were observed after PLC hydrolysis.
      Interestingly, only the PLC-released soluble form of the 115-kDa metalloenzyme,
      and not the membrane-anchored form, displayed proteolytic activity, demonstrating
      that cleavage of the GPI anchor can lead to enzymatic activation.

PMID- 12192530
TI  - Isolation and characterization of a strain of Bacillus thuringiensis ssp.
      kurstaki containing a new delta-endotoxin gene.
AB  - A strain of Bacillus thuringiensis that showed significantly high toxicity to
      Plutella xylostella and Spodoptera exigua was isolated from a Korean soil sample
      and characterized. The isolate, named B. thuringiensis K1, was determined to
      belong to ssp. kurstaki (H3a3b3c) type by an H antisera agglutination test and
      produced bipyramidal inclusions. Plasmid pattern of K1 was different from that of
      the reference strain, ssp. kurstaki HD-1, but the parasporal inclusion protein
      profile of K1 had two major bands that were similar in size to those of ssp.
      kurstaki HD-1. To verify the delta-endotoxin gene types of K1, PCR analysis with
      specific cry gene primers was performed to show that K1 contained a new cry gene
      in addition to cry1Aa, cry1Ab, cry1Ac, cry1E and cry2 genes. PCR-amplified region
      of the new cry gene, cryX, showed 79% similarity to cry1Fa1 gene (GenBank
      Accession No. M63897). In an insect toxicity assay, K1 had higher toxicity
      against Plutella xylostella and S. exigua than ssp. kurstaki HD-1.

PMID- 12192531
TI  - Conservation of XYN11A and XYN11B xylanase genes in Bipolaris sorghicola,
      Cochliobolus sativus, Cochliobolus heterostrophus, and Cochliobolus spicifer.
AB  - Two types of xylanase gene, XYN11A ( XYL1) and XYN11B ( XYL2), were amplified by
      PCR and partially sequenced in four phytopathogenic species of the ascomycete
      fungal genus Cochliobolus (anamorph genus Bipolaris). Three of the species, C.
      heterostrophus ( B. maydis), C. sativus ( B. sorokiniana), and Bipolaris
      sorghicola (no teleomorph known), are interrelated; the fourth, C. spicifer ( B.
      spicifera), was found, through analysis of the 5.8S RNA and internal transcribed
      spacer (ITS) sequences of its ribosomal DNA, to be more distantly related to the
      other three. Isolates from all four species contain orthologous XYN11A and XYN11B
      genes, but a set of laboratory strains of C. heterostrophus gave no product
      corresponding to the XYN11B gene. The patterns of evolution of the two xylanase
      genes and ribosomal DNA sequences are mutually consistent; the results indicate
      that the two genes were present in the common ancestor of all Cochliobolus
      species and are evolving independently of each other.

PMID- 12192532
TI  - Quality of life and patient satisfaction after reoperation for primary
      hyperparathyroidism: analysis of long-term results.
AB  - Morbidity after reoperation for persistent or recurrent primary
      hyperparathyroidism (pHPT) is higher than after primary surgery. According to our
      experience, there is a contrast between postoperative normalization of laboratory
      parameters and the quality of life/patient satisfaction after reoperation.
      Therefore the aim of the study was to analyze the outcomes of reoperations in
      comparison to primary surgery. We evaluated the patients' reported quality of
      life using the SF-36 (an accepted health status assessment tool) and complete
      prospectively documented perioperative and follow-up data including postoperative
      complications. Additionally, we searched for reasons why primary surgical
      intervention did not succeed. In a prospective cohort study the perioperative
      data of 653 consecutive patients with pHPT, including 75 reoperated patients
      (11.5%) who underwent parathyroidectomy between 1987 and 1999, were evaluated by
      uni- and multivariate analysis. At a median 78 months (6-156 months)
      postoperatively, all patients underwent a planned follow-up that included the SF
      36, physical examination, and laboratory investigations. A total of 51 reoperated
      patients were available for follow-up. Postoperative alleviation of symptoms or
      being symptom-free was reported by 70.6%. Patients after reoperation had lower SF
      36 scores in all health domains postoperatively than patients after a primary
      operation. Of the reoperated patients, 19.6% stated that after evaluating the
      development of their complaints they would not consent to reoperation again.
      Subgroup analysis showed that 80% of patients with postoperatively persistent
      pHPT, 60% of those who did not observe symptom alleviation, and 44% of those
      after sternotomy were in the group of dissatisfied patients. Surprisingly, none
      of the patients with more than one reoperation, only two of the five patients
      with permanent recurrent laryngeal nerve injury, and only one of the four
      patients with persistent hypoparathyroidism were dissatisfied overall.
      Parathyroidectomy resulted in normocalcemia in 90.2% of the reoperated patients,
      with an operative morbidity of 27.4% and no mortality. After an unsuccessful
      operation for pHPT, patients should be treated at an expert center to avoid
      persistent hypercalcemia. Reoperations necessitating sternotomy should be
      restricted to patients with severe symptoms and signs.

PMID- 12192533
TI  - Efficacy and safety of doxazosin for perioperative management of patients with
      pheochromocytoma.
AB  - Despite adverse side effects, phenoxybenzamine has been widely used for the
      preoperative management of patients with pheochromocytoma. Doxazosin, a specific
      a 1-adrenoceptor antagonist, has a pharmacologic profile more suited to
      controlling blood pressure in such patients. A sequential study of 35 patients
      with pheochromocytoma encompassed a definite and prescribed change in
      preoperative drug management from phenoxybenzamine to doxazosin. Hemodynamic,
      pharmacologic, and biochemical indicators of a- and b-adrenoceptor blockade were
      measured before, during, and after anesthesia and surgery in 8 patients
      pretreated with phenoxybenzamine and 27 patients pretreated with doxazosin.
      Doxazosin (2-16 mg/day) was as effective as phenoxybenzamine in controlling
      arterial pressure and heart rate before and during surgery, but doxazosin caused
      fewer undesirable side effects both before and after surgery. Following
      phenoxybenzamine therapy substantial a 1-adrenoceptor blockade, detected as a
      right shift of phenylephrine dose-response curves, persisted for more than 2 days
      postoperatively, whereas after doxazosin it was undetectable on the first
      postoperative day. Doxazosin provided safe, efficacious pre- and perioperative
      control of arterial pressure. In patients with predominantly norepinephrine
      secreting tumors, pretreatment 24-hour urinary norepinephrine excretion gave an
      indication of the daily doxazosin requirement.

PMID- 12192534
TI  - Immunotherapeutic potential of whole tumour cells.
AB  - Despite the identification of tumour antigens and their subsequent generation in
      subunit form for use as cancer vaccines, whole tumour cells remain a potent
      vehicle for generating anti-tumour immunity. This is because tumour cells express
      an array of target antigens for the immune system to react against, avoiding
      problems associated with major histocompatibility complex (MHC)-restricted
      epitope identification for individual patients. Furthermore, whole cells are
      relatively simple to propagate and are potentially efficient at contributing to
      the process of T cell priming. However, whole cells can also possess properties
      that allow for immune evasion, and so the question remains of how to enhance the
      immune response against tumour cells so that they are rejected. Scenarios where
      whole tumour cells may be utilised in immunotherapy include autologous tumour
      cell vaccines generated from resected primary tumour, allogeneic (MHC-disparate)
      cross-reactive tumour cell line vaccines, and immunotherapy of tumours in situ.
      Since tumour cells are considered poorly immunogenic, mainly because they express
      self-antigens in a non-stimulatory context, the environment of the tumour cells
      may have to be modified to become stimulatory by using immunological adjuvants.
      Recent studies have re-evaluated the relative roles of direct and cross-priming
      in generating anti-tumour immunity and have highlighted the need to circumvent
      immune evasion.

PMID- 12192535
TI  - Anti-tumor activities of the angiogenesis inhibitors interferon-inducible protein
      10 and the calreticulin fragment vasostatin.
AB  - Tumor growth depends upon an adequate supply of oxygen and nutrients achieved
      through angiogenesis and maintenance of an intact tumor vasculature. Therapy with
      individual agents that target new vessel formation or existing vessels has
      suppressed experimental tumor growth, but rarely resulted in the eradication of
      tumors. We therefore tested the combined anti-tumor activity of vasostatin and
      interferon-inducible protein-10 (IP-10), agents that differently target the tumor
      vasculature. Vasostatin, a selective and direct inhibitor of endothelial cell
      proliferation, significantly reduced Burkitt tumor growth and tumor vessel
      density. IP-10, an "angiotoxic" chemokine, caused vascular damage and focal
      necrosis in Burkitt tumors. When combined, vasostatin plus IP-10 reduced tumor
      growth more effectively than each agent alone, but complete tumor regression was
      not observed. Microscopically, these tumors displayed focal necrosis and
      reduction in vessel density. Combination therapy with the inhibitors of
      angiogenesis vasostatin and IP-10 is effective in reducing the rate of tumor
      growth but fails to induce tumor regression, suggesting that curative treatment
      may require supplemental drugs targeting directly the tumor cells.

PMID- 12192536
TI  - Cell fusion: an approach to generating constitutively proliferating human tumor
      antigen-presenting cells.
AB  - Somatic cell hybrids of HLA-A2(+) EBV-transformed B- or dendritic cells (DC) and
      allogeneic HLA-A2(-) melanoma cell line Me15 were obtained by in vitro
      electrofusion using an electroporator. Before fusion, melanoma cells were stably
      transfected with green fluorescent marker protein (GFP) and neomycin resistance
      gene (neo(+)). Stably growing hybrid antigen-presenting cells (HAPC) expressing
      HLA-DR and HLA-A2 (or HLA-A30/31), and melanoma-associated antigens (MART-1,
      gp100) were selected by a double strategy of immunomagnetic MACS and neomycin
      selection. Fusion efficiency ranged between 3% and 18% (mean: 8.0+/-4.7%) as
      defined by simultaneous GFP and HLA-A2 detection. Expression of melanoma
      associated antigens (MART-1, gp100) in hybrid cells was determined by reverse
      transcription-polymerase chain reaction (RT-PCR). HLA-restricted antigen-specific
      presentation of melanoma antigens was demonstrated by killing of semi-allogenic
      HAPC by HLA-A2-restricted MART-1 or gp100-specific cytotoxic T lymphocyte (CTL)
      clones. HLA restriction and antigen specificity were confirmed by inhibition of
      specific cytotoxicity by anti-HLA antibodies and cold target inhibition. During
      long-term (42-70 days) neomycin selection of HAPC, a drastic loss of antigen
      presenting cell (APC)-derived determinants (e.g. HLA-DR, HLA-A2) was observed
      which, however, could be "reversed" by repeated MACSorting (days 10, 21 and 49).
      Our method allows the generation of semi-allogenic HAPC that constitutively
      proliferate in vitro. This opens the possibility of establishing a number of
      tumor-APC hybrids expressing defined HLA haplotypes and tumor antigens, of
      investigating their specific properties (e.g. antigen processing), and testing
      their diagnostic or therapeutic potential.

PMID- 12192537
TI  - Protein A-induced apoptosis of cancer cells is effected by soluble immune
      mediators.
AB  - Since Protein A (PA) of Staphylococcus aureus has been documented to have both
      antitumor and immunostimulatory properties, we attempted to determine whether PA
      induced tumor cell death was effected through the immune system of the host, and
      analyze the mechanisms of such anti-tumor activity. For in vivo studies,
      Ehrlich's ascites carcinoma (EAC) cells were inoculated into the peritoneal
      cavity of Swiss albino mice. PA (1 micro g/20 g body weight) was injected
      biweekly for 2 weeks. To determine the role of immunomodulators in PA-induced
      tumor cell death, EAC were co-cultured with PA-primed splenic cells or with the
      spent medium of the same. Our results indicated a "two-step" mechanism of the
      induction of apoptosis in tumor cells, by PA, i.e. (1) activation of the immune
      system of the host to release different apoptogenic factors like tumor necrosis
      factor-alpha (TNF-alpha) and nitric oxide (NO); and (2) induction of EAC
      apoptosis by these soluble immune mediators through the up-regulation of pro
      apoptotic factors (p53 and Bax) and down-regulation of anti-apoptotic factor (Bcl
      2), resulting in the activation of caspase-3. The present observations provide
      additional findings on an approach to cancer immunotherapy that causes
      apoptogenic insult to cancer cells.

PMID- 12192538
TI  - Suppression of in vivo tumorigenicity of rat hepatoma cell line KDH-8 cells by
      soluble TGF-beta receptor type II.
AB  - We have previously reported that transforming growth factor beta (TGF-beta)
      produced by rat hepatoma cell line KDH-8 cells suppressed the interleukin-2 (IL
      2) production of T cells and the tumoricidal activity of macrophages in KDH-8
      tumor-bearing rats and that the inhibition of TGF-beta production by low-dose
      bleomycin restored these activities significantly. In this study, we established
      three transfectant clones with stable expression of soluble TGF-beta receptor
      type II (sTRII), namely KT1, KT2 and KT3, and one with an empty vector used as
      control vector (KV), and then investigated the effects of sTRII on the
      tumorigenicity of KDH-8 cells and immune responses in syngeneic Wistar King
      Aptekman/Hok (WKAH) rats. We found that sTRII expressed in sTRII transfectants
      could abolish growth inhibition of Mv1Lu cells by TGF-beta1 produced by the cells
      themselves, and that tumor growth of KT2 and KT3 clones in vivo was suppressed
      significantly compared with that of parent, KV and KT1 clones. Furthermore, we
      demonstrated that IL-2 production of splenocytes and IL12p40 mRNA expression in
      tumor tissues were restored in rats inoculated with KT2 and KT3 clones, whereas
      such restoration was not observed in rats inoculated with parent, KV and KT1
      clones. Combined with a low expression of sTRII in KT1 tumor tissues, these
      results suggest that sTRII may to some extent be able to abolish the tumor
      promoting activity of TGF-beta, and imply that sTRII might have a therapeutic
      effect on TGF-beta-producing tumors.

PMID- 12192539
TI  - Multiple mechanisms generate HLA class I altered phenotypes in laryngeal
      carcinomas: high frequency of HLA haplotype loss associated with loss of
      heterozygosity in chromosome region 6p21.
AB  - Major histocompatibility complex (MHC) class I loss or downregulation in cancer
      cells is a major immune escape route used by a large variety of human tumors to
      evade anti-tumor immune responses mediated by cytotoxic T lymphocytes. Multiple
      mechanisms are responsible for such HLA class I alterations. However, the precise
      frequency of these molecular defects has not been clearly determined in tumors
      derived from specific tissues. To analyze such defects we aim to define the major
      HLA class I-altered phenotypes in different tumor types. In this paper we report
      on HLA class I expression in 70 laryngeal carcinomas. We used immunohistological
      techniques with a highly selective panel of anti-HLA monoclonal antibodies (mAb),
      and polymerase chain reaction (PCR) microsatellite amplification of previously
      selected microsatellite markers (STR) located in chromosome 6 and 15. DNA was
      obtained from microdissected tumor tissues and surrounding stroma to define the
      loss of heterozygosity (LOH) associated with chromosome 6p21. Our results showed
      that LOH in chromosome 6 produced HLA haplotype loss (phenotype II) in 36% of the
      tumors. In addition, HLA class I total loss (phenotype I) was found in 11%; HLA A
      or B locus downregulation (phenotype III) was detected in 20%; and HLA class I
      allelic loss (phenotype IV) in 10% of all cases. We sometimes observed two or
      more associated mechanisms in the same HLA-altered phenotype, such as LOH and HLA
      total loss in phenotype I. In only 23% of tumors it was not possible to identify
      any HLA class I alteration. We conclude that the combination of
      immunohistological techniques and molecular analysis of tumor DNA obtained from
      microdissected tumor tissues provides a means for the first time of determining
      the actual frequency of the major HLA class I-altered phenotypes in laryngeal
      carcinomas.

PMID- 12192540
TI  - Iodine deficiency in Europe and its consequences: an update.
AB  - This paper updates the information on the prevalence of the disorders induced by
      iodine deficiency (IDD) in Europe. Thirty-two European countries were still
      affected by mild to severe iodine deficiency in the late 1990s. The most severely
      affected countries were in Eastern Europe, including Central Asia, but Western
      Europe was also still affected. National surveys recently conducted in 11 of
      these countries show that, with the exception of the Netherlands, none has yet
      reached a state of iodine sufficiency, though very significant improvement in the
      situation has been evidenced in many of them, e.g. Poland, Bulgaria and
      Macedonia. The consequences of persisting iodine deficiency are goitre,
      hyperavidity of the thyroid for iodide (which increases the risk of thyroid
      irradiation in the event of a nuclear accident) and subclinical hypothyroidism
      during pregnancy and early infant (with a concomitant risk of minor brain damage
      and irreversible impairment of the neuropsychointellectual development of
      offspring). Access to iodised salt at the household level in European countries
      affected by IDD increased from 5%-10% in 1990 to 28% in 1999. This constitutes
      encouraging progress. However, in terms of access of iodine-deficient countries
      to iodised salt, Europe remains the worst region in the world, as shown by the
      fact that the mean figure worldwide in 1999 was 68%. In Latin America it even
      reached 90%. Salt iodisation has to be further implemented in Europe. Until that
      goal is achieved, iodine supplementation in those groups most sensitive to the
      effects of iodine deficiency (pregnant and lactating women and young infants)
      will have to be considered in the most severely affected areas.

PMID- 12192542
TI  - The continuing importance of thyroid scintigraphy in the era of high-resolution
      ultrasound.
AB  - At the molecular level, the uptake of radioiodine and pertechnetate is
      proportional to the expression of the thyroidal sodium/iodine symporter (NIS).
      Qualitative and quantitative scintigraphic evaluation of the thyroid is performed
      with a gamma camera fitted with an on-line computer system and enables
      determination of the iodine uptake or the technetium uptake (TCTU) as an iodine
      clearance equivalent. Despite new molecular genetic insights into congenital
      hypothyroidism, the iodine-123 or pertechnetate scan remains the most accurate
      test for the detection of ectopic thyroid tissue. Following the identification of
      specific mutations of the genes coding for the NIS, thyroid peroxidase and
      pendrin, the discharge test has lost its role in establishing the diagnosis of
      inherited dyshormonogenesis, but it is still of value in the assessment of defect
      severity. In PDS mutations the test can be used to establish the diagnosis of
      syndromic disease. Quantitative pertechnetate scintigraphy is the most sensitive
      and specific technique for the diagnosis and quantification of thyroid autonomy.
      The method has proved to be valuable in risk stratification of spontaneous or
      iodine-induced hyperthyroidism, in the estimation of the target volume prior to
      radioiodine therapy and in the evaluation of therapeutic success after definitive
      treatment. In iodine deficiency areas the thyroid scan remains indispensable for
      the functional characterisation of a thyroid nodule and is still a first-line
      diagnostic procedure in cases of suspected thyroid malignancy. This is especially
      of importance in patients with Graves' disease, among whom a relatively high
      prevalence of cancer has been found in cold thyroid nodules. While determination
      of the TCTU is without any value in the differentiation between autoimmune
      thyroiditis and Graves' disease in most cases, it is of substantial importance in
      the differentiation between hyperthyroid autoimmune thyroiditis and Graves'
      disease.

PMID- 12192541
TI  - Autoimmunity in thyroid disease.
AB  - The autoimmune thyroid diseases, Graves' disease and autoimmune hypothyroidism,
      represent the two ends of a disease spectrum where an immune response is directed
      against the thyroid gland. In Graves' disease, antibodies directed against the
      thyrotropin receptor (TSH-R) lead to the development of glandular overactivity,
      while in autoimmune hypothyroidism, cell-mediated and humoral thyroid injury
      leads to destruction of thyroid tissue and thyroid hormone deficiency. The
      mechanisms by which these diseases develop are unknown, although it is likely
      that both diseases occur in genetically susceptible individuals exposed to a
      permissive environment. A number of environmental factors have been postulated to
      be involved in the development of autoimmune thyroid disease. There is, however,
      no direct evidence to support clear causality. Susceptibility loci within immune
      response genes have been identified although a significant component of the
      genetic predisposition to disease remains unknown. This review will focus on some
      of the studies designed to identify genes that confer susceptibility to the
      autoimmune disease process within the thyroid gland.

PMID- 12192543
TI  - Thyroid disorders in children from birth to adolescence.
AB  - Thyroid hormones play a crucial role as a regulator of growth, of nervous system
      myelination, of metabolism, and of organ functions. Disorders affecting the
      thyroid gland represent the most common endocrinopathies in childhood. The
      etiology and clinical presentation of thyroid disorders in children and
      adolescents substantially differ from that in adults. Thus, pediatric medical
      care requires an appreciation of distinct characteristics of thyroid function and
      dysfunction in childhood and adolescence. Early diagnosis and treatment are
      essential to prevent irreversible and permanent nervous system damage and
      developmental delay, especially in infants as they are extremely vulnerable to
      thyroid dysfunction. Therefore, as well as reviewing distinct features of
      disorders with hypothyroidism, hyperthyroidism and normal thyroid function in
      childhood and adolescence, this article will also focus on important aspects of
      pre- and postnatal thyroid development and physiology.

PMID- 12192544
TI  - An update on thyroid surgery.
AB  - Surgery has been the treatment of choice for many disorders of the thyroid gland,
      both benign and malignant, for many decades. However, surgery has not been
      invariable but has continued to change in accordance with research results. In
      benign cases, surgery has generally evolved to be as organ preserving as
      possible. In several instances, however, a more radical extent of resection seems
      justified in order to ensure that the risk of recurrence is as low as possible.
      For instance, total thyroidectomy may be beneficial in patients with endemic
      multinodular goitre or young patients with Graves' disease and accompanying cold
      nodules or high levels of autoantibodies. Several tools, e.g. magnifying glasses,
      bipolar coagulation forceps and neuromonitoring, are available to identify and
      preserve the recurrent laryngeal nerve and the parathyroid glands, hence keeping
      the morbidity at a low level. Most recently, minimally invasive surgery has been
      successfully used in treating both benign and malignant disorders of the thyroid
      gland. In the case of malignant disorders, minimally invasive surgery may become
      an attractive alternative to open surgery if a limited surgical extent is
      justified, e.g. in patients with micro-PTC (papillary thyroid carcinoma, diameter
      less than 1 cm). Whether a limited surgical approach is also justified in other
      cases, e.g. in any patient with intrathyroidal PTC or patients with micro-FTC
      (follicular thyroid carcinoma), remains to be shown and is the subject of ongoing
      investigations. One of the most intriguing recent discoveries is the
      identification of genotype-phenotype correlations in patients with hereditary
      medullary thyroid carcinoma. In these patients, the timing and extent of surgery
      may depend not only on the patient's age and serum levels of the tumour marker
      calcitonin but also on the specific germline RET proto-oncogene mutation. Surgery
      will certainly continue to play an important role in the treatment of thyroid
      diseases and may be increasingly based on individual findings instead of general
      recommendations.

PMID- 12192545
TI  - Strategies of radioiodine therapy for Graves' disease.
AB  - Several therapeutic options are available for the treatment of Graves' disease
      (GD), including long-term antithyroid drug medication (ATD), near-total resection
      (NTR) and radioiodine therapy (RIT). These treatments are used with different
      frequencies depending on geographical location, size of the goitre, age of the
      patient and experience of the physician. It should be noted that RIT is still
      being applied more frequently in the United States than in Europe. Despite the
      fact that RIT was introduced as long ago as 1941, several questions are still the
      subject of debate: Should a fixed dose or a calculated dose be used. If the dose
      is calculated, how many Grays (Gy) should be delivered to the thyroid? What is
      the goal of RIT in GD? Which factors, including ATD, influence the outcome of
      RIT? Is RIT appropriate in GD with Graves' ophthalmopathy (GO)? Although not all
      these questions have been answered yet, conclusions can be derived regarding a
      general strategy for use of RIT in GD. As with surgery, the goal of RIT in GD is
      euthyroidism with or without L-thyroxine medication. There is a clear advantage
      of dose calculation over use of a fixed dose because the only factor influencing
      the outcome is the dose delivered to a certain thyroid volume. To minimise
      recurrent hyperthyroidism, an ablative approach using a delivered dose of 250 Gy
      is widely accepted. Beside pretherapeutic T(3) levels, thyroid volume and 24-h
      thyroid uptake, ATD may influence the outcome of RIT. Today it is accepted by
      most thyroidologists that, if ATD medication is necessary in overt
      hyperthyroidism, it should be withdrawn at least 2 days before RIT. In patients
      with GD and GO, RIT may worsen GO. If RIT is performed in GO it should be done
      under a 3-month steroid medication regimen. In conclusion, RIT can be considered
      an appropriate and cost-effective therapy in GD, although the decision regarding
      treatment should be taken on an individual basis, paying due respect to the
      course and severity of disease, the presence of GO and, last but not least, the
      wishes of the patient.

PMID- 12192546
TI  - Management of thyroid eye disease.
AB  - Thyroid eye disease (TED) is the most frequent extrathyroidal manifestation of
      Graves' disease. In most instances it is mild and non-progressive, but in 3%-5%
      of cases it is severe. Non-severe TED requires only supportive measures, such as
      eye ointments, sunglasses and prisms. By contrast, severe TED requires aggressive
      treatment, either medical (high-dose glucocorticoids, orbital radiotherapy) or
      surgical (orbital decompression). The choice of treatment relies on the
      assessment of both TED severity and activity. Removal of controllable risk
      factors, especially cigarette smoking, is important to improve the course and the
      therapeutic outcome. A coordinated approach to the treatment of hyperthyroidism
      and TED is also required. Novel promising treatments, to be verified in large
      series of patients, include somatostatin analogues and cytokine antagonists.

PMID- 12192547
TI  - Radioiodine therapy of euthyroid multinodular goitres.
AB  - Euthyroid multinodular goitre is caused by excessive replication of thyroid
      epithelial cells, due to various stimuli. With time there is a gradual increase
      in size and in nodularity. The clinical manifestations arise solely from thyroid
      enlargement. Treatment of euthyroid multinodular goitre is indicated only when
      thyroid enlargement causes symptoms of obstruction, such as dysphagia and
      dyspnoea. Treatment options are radioiodine (iodine-131), surgery and TSH
      suppression therapy. In this review we compare these treatment modalities. In our
      opinion, radioiodine is the treatment of choice in elderly patients, in patients
      in whom surgery is contra-indicated and in patients who are unwilling to undergo
      surgery. The life-time risk of fatal and non-fatal cancer due to radioiodine is
      negligible in patients over 65 years of age, compared with the life-time risk of
      fatal cancer in the non-exposed population.

PMID- 12192548
TI  - Radioiodine therapy of thyroid autonomy.
AB  - Over half a century, treatment of thyroid autonomy with an oral dose of iodine
      131 has proven to be effective. The optimum management strategy for the patient
      is, however, still a matter of debate. The article provides an overview of the
      pathogenesis of functional autonomy and its clinical relevance. According to the
      guidelines on both sides of the Atlantic, radioiodine treatment is considered the
      most comfortable and economical approach to the treatment of the toxic nodular
      goitre. Some differences in the preparation procedures in the guidelines of the
      American and the German Society of Nuclear Medicine are discussed with respect to
      therapy results and the subtypes of thyroid autonomy. The results of studies are
      summarised concerning changes in thyroid function and thyroid volume after a
      course of radioiodine treatment. Therapy-related risks, such as immunogenic
      hypothyroidism or thyroid cancer, are discussed. (131)I treatment of functional
      autonomy and hyperthyroidism is considered an effective and safe procedure.

PMID- 12192549
TI  - Radioiodine therapy for papillary and follicular thyroid carcinoma.
AB  - Radioiodine ((131)I) therapy is used in patients with papillary and follicular
      thyroid carcinoma for ablation of thyroid remnants and for treatment of
      persistent or recurrent disease. It should be used selectively, i.e. only in
      those patients for whom a clinical benefit may be expected.

PMID- 12192550
TI  - Radioiodine therapy and thyrostatic drugs and iodine.
AB  - Radioiodine therapy is now the most common definite treatment for persistent
      hyperthyroidism. The outcome of radioiodine therapy depends mainly on the
      absorbed energy dose in the diseased thyroid tissue. The administered activity
      and the resulting target dose in the thyroid depend on both the biokinetics of
      radioiodine and the actual therapeutic effect of radioiodine in the thyroid.
      Thyrostatic drugs have a major influence on the kinetics of radioiodine in the
      thyroid and may additionally have a radioprotective effect. Pre-treatment with
      thyrostatic medication lowers the effective half-life and uptake of radioiodine.
      This can reduce the target dose in the thyroid and have a negative influence on
      the outcome of the therapy. Discontinuation of medication shortly before
      radioiodine administration can increase the absorbed energy dose in the thyroid
      without increasing the whole-body exposure to radiation as much as would a higher
      or second radioiodine administration. Furthermore, administration of non
      radioactive iodine-127 2-3 days after radioiodine administration can also
      increase the effective half-life of radioiodine in the thyroid. Thus, improving
      the biokinetics of radioiodine will allow lower activities to be administered
      with lower effective doses to the rest of the body, while achieving an equally
      effective target dose in the thyroid.

PMID- 12192551
TI  - Follow-up of differentiated thyroid cancer.
AB  - The aim of post-surgical follow-up for differentiated thyroid carcinoma is the
      early identification of the small proportion of patients who have residual
      disease or develop a recurrence. When total thyroidectomy and radioiodine
      ablation have been the initial treatment, three powerful tools are available for
      the follow-up: basal and TSH-stimulated serum thyroglobulin (Tg) measurement,
      iodine-131 whole body scan (WBS) and neck ultrasound. Serum Tg measurement is the
      most sensitive and specific marker of differentiated thyroid cancer. Undetectable
      serum Tg levels are found in the large majority of disease-free patients, while
      elevated concentrations of serum Tg are associated with the presence of residual
      or metastatic thyroid tissue. In the last case, WBS under TSH stimulation (either
      after withdrawal of L-thyroxine therapy or after recombinant human TSH
      stimulation) and neck ultrasound are the most informative tests for the detection
      of distant or local metastases, respectively, that require more appropriate
      treatment (surgery and/or radioiodine therapy). Using this strategy, most
      patients will achieve definitive cure and will have a normal quality of life.

PMID- 12192552
TI  - Non-medical exposure to radioiodines and thyroid cancer.
AB  - The Chernobyl accident, which occurred 32 years after the accidental exposure of
      Marshall islanders, resulted in the exposure of neighbouring populations to a
      mixture of iodine isotopes and in an increased incidence of thyroid cancer. The
      highest thyroid doses were received by the youngest age groups. This review
      describes the existing evidence, and examines factors that may have increased the
      risk. It also stresses problems with contemporary thyroid measurements, and the
      lack of information on the sensitivity of the thyroid to short-lived iodine
      isotopes and iodine-131. Practical considerations for nuclear physicians,
      epidemiologists and thyroidologists are discussed in the light of this major
      accident.

PMID- 12192553
TI  - Patients' and personnel's perceptions of service quality and patient satisfaction
      in nuclear medicine.
AB  - Patients' and personnel's perceptions of service quality were analysed to
      position nuclear medicine organisations in the service triangle theory of Haywood
      Farmer [ Int J Production and Operations Management 1988; 6:19-29]. After
      distinguishing the service quality dimensions of nuclear medicine, a comparison
      was made between the service quality perceptions of patients ( n=259) and those
      of personnel ( n=24). We examined the importance of different service quality
      dimensions by studying their relationship to patient satisfaction. The proposed
      five dimensions of SERVQUAL, the most commonly used service quality measurement
      scale, were not confirmed. Patients considered tangibles and assurance as one
      dimension, while the original empathy dimension was separated into empathy and
      convenience. Personnel perceived all service quality dimensions as less good than
      did patients, except for empathy. Results indicated that patients' perception of
      service quality was correlated with patient satisfaction, especially in terms of
      reliability and tangibles-assurance. Based on these service quality dimensions,
      we suggest that nuclear medicine services need to optimise their physical and
      process component and the technical skills of personnel.

PMID- 12192554
TI  - Radioiodine therapy in Graves' disease based on tissue-absorbed dose
      calculations: effect of pre-treatment thyroid volume on clinical outcome.
AB  - This study was performed with three aims. The first was to analyse the
      effectiveness of radioiodine therapy in Graves' disease patients with and without
      goitres under conditions of mild iodine deficiency using several tissue-absorbed
      doses. The second aim was to detect further parameters which might be predictive
      for treatment outcome. Finally, we wished to determine the deviation of the
      therapeutically achieved dose from that intended. Activities of 185-2,220 MBq
      radioiodine were calculated by means of Marinelli's formula to deliver doses of
      150, 200 or 300 Gy to the thyroids of 224 patients with Graves' disease and
      goitres up to 130 ml in volume. Control of hyperthyroidism, change in thyroid
      volume and thyrotropin-receptor antibodies were evaluated 15+/-9 months after
      treatment for each dose. The results were further evaluated with respect to pre
      treatment parameters which might be predictive for therapy outcome. Thyroidal
      radioiodine uptake was measured every day during therapy to determine the
      therapeutically achieved target dose and its coefficient of variation. There was
      a significant dose dependency in therapeutic outcome: frequency of hypothyroidism
      increased from 27.4% after 150 Gy to 67.7% after 300 Gy, while the frequency of
      persistent hyperthyroidism decreased from 27.4% after 150 Gy to 8.1% after 300
      Gy. Patients who became hypothyroid had a maximum thyroid volume of 42 ml and
      received a target dose of 256+/-80 Gy. The coefficient of variation for the
      achieved target dose ranged between 27.7% for 150 Gy and 17.8% for 300 Gy. When
      analysing further factors which might influence therapeutic outcome, only pre
      treatment thyroid volume showed a significant relationship to the result of
      treatment. It is concluded that a target dose of 250 Gy is essential to achieve
      hypothyroidism within 1 year after radioiodine therapy in Graves' disease
      patients with goitres up to 40 ml in volume. Patients with larger goitres might
      need higher doses.

PMID- 12192555
TI  - Gastric emptying in patients with vitamin B(12) deficiency.
AB  - The clinical presentation of patients with vitamin B(12) deficiency varies in a
      spectrum ranging from haematological disorders to neuropsychiatric diseases. In
      rare cases, orthostatic hypotension, impotence, constipation and urinary
      retention have been attributed to autonomic nervous system dysfunction due to
      vitamin B(12) deficiency. The aim of this study was to evaluate the effect of
      vitamin B(12) deficiency on autonomic nervous system function by studying gastric
      emptying times ( T(1/2)). Twenty patients with newly diagnosed vitamin B(12)
      deficiency and 12 control patients with gastritis and normal vitamin B(12) levels
      were enrolled in this study. Gastroduodenoscopy, endoscopic biopsy,
      histopathological evaluation of the biopsy specimens and radionuclide gastric
      emptying studies were performed. After vitamin B(12) replacement therapy for 3
      months, radionuclide gastric emptying studies were repeated. Mean gastric
      emptying T(1/2) in patients before and after treatment and in controls were
      103.83+/-48.80 min, 90.00+/-17.29 min and 74.55+/-8.52 min, respectively. The
      difference in mean gastric emptying T(1/2) between patients before treatment and
      controls was statistically significant ( P<0.01). The statistically significant
      difference persisted after vitamin B(12) treatment ( P<0.05), though mean gastric
      emptying T(1/2) was somewhat shorter. There were no positive or negative
      correlations between gastric emptying T(1/2) and the following parameters:
      haemoglobin, vitamin B(12) level and Helicobacter pylori positivity. In
      conclusion, gastric emptying T(1/2) was prolonged in patients with vitamin B(12)
      deficiency and this prolongation was not corrected after vitamin B(12)
      replacement therapy. Although autonomic nervous system dysfunction due to vitamin
      B(12) deficiency rarely gives rise to clinical manifestations, latent dysfunction
      demonstrated by laboratory tests seems to be a frequent phenomenon. The level of
      vitamin B(12) does not correlate with the degree of autonomic nervous system
      dysfunction measured by radionuclide gastric emptying studies.

PMID- 12192556
TI  - Leakage assessment in adjustable laparoscopic gastric banding: radiography versus
      (99m)Tc-pertechnetate scintigraphy.
AB  - The least invasive of all surgical weight-lowering procedures is the adjustable
      laparoscopic gastric banding (ALGB) technique. A rare complication (0.9%-1.8% of
      patients) but one that may require surgical revision is leakage of the gastric
      banding device. This paper reports on the usefulness of technetium-99m
      scintigraphy for the assessment of gastric band leaks as compared with
      radiography. Between March 1997 and October 2001, 23 obese patients (20 women and
      3 men; mean age 35 years; range 23-60 years; mean body mass index before gastric
      banding procedure, 39.2 kg/m(2); range 29.3-52.1 kg/m(2)) were referred for
      exclusion of gastric banding leakage by means of radiography and (99m)Tc
      pertechnetate scintigraphy. Both procedures were performed on the same day in all
      patients. Two patients underwent both procedures, respectively two and three
      times. A total of 27 radiographic and scintigraphic examinations were performed.
      Radiographs were judged positive for leakage when escape of contrast agent
      through a defect in the gastric banding device was visualised or when indirect
      criteria, e.g. smooth passage of barium suspension through the stoma after
      injection of contrast agent, were present. Scintigraphic images were judged
      positive when tracer disappearance out of the banding device and uptake in the
      thyroid gland as well as enhancement of the gastric mucosa were observed 30 min
      and/or 3 h post injection. Overall sensitivity, specificity and accuracy for
      radiography and (99m)Tc scintigraphy were 81.8% vs 81.8%, 75% vs 100% and 77.7%
      vs 92.6%. Leakage from the reservoir or the connecting tube is a late
      complication of ALGB. The presented data suggest that (99m)Tc-pertechnetate
      scintigraphy is more efficient than radiography in determining the presence of
      such leaks.

PMID- 12192557
TI  - Usefulness of (18)F-FDG PET in the post-therapy surveillance of endometrial
      carcinoma.
AB  - The aim of this study was to assess the usefulness of fluorine-18 fluoro-2-deoxy-
      D-glucose positron emission tomography (FDG PET) in the post-therapy surveillance
      of endometrial carcinomas. Forty-one fully corrected whole-body PET studies were
      performed in 34 women with previously treated endometrial cancers as a part of
      their follow-up programme. In 28 studies, FDG PET was indicated to localise a
      recurrence suspected at the control visits on the basis of clinical examination
      and/or radiological abnormalities (chest X-ray, CT or MRI) and/or elevated tumour
      marker levels (CA125, CEA). Another 13 studies were performed as a simple
      surveillance procedure. Overall, in 26 studies PET detected recurrent disease,
      which was confirmed either by histology ( n=7) or by clinical and radiological
      outcomes ( n=19). In 88% of the cases, the PET findings confirmed recurrence
      suggested by routine follow-up. In the remaining 12% of cases, PET detected
      asymptomatic recurrences that were unsuspected at the control visits. Whole-body
      PET accurately localised the site of confirmed recurrences as being above and
      below the diaphragm in 50%, only below the diaphragm in 35% and only above the
      diaphragm in 15%. In one patient, however, PET missed microscopic lung metastases
      shown on thoracic CT, and in three studies, metabolic imaging results were not
      confirmed. In 11 of 12 negative PET studies, no subsequent clinical or
      radiological recurrences were observed with a median follow-up of 10 months.
      Overall, the results of PET agreed well with the final diagnosis (Cohen's kappa
      coefficient =0.78). In 9/26 patients (35%) with confirmed recurrences, the PET
      findings significantly altered the treatment choice by detecting either
      clinically or radiologically unsuspected distant metastases. The sensitivity,
      specificity, diagnostic accuracy and positive and negative predictive values of
      FDG PET imaging in the post-therapy surveillance of endometrial carcinomas were
      96%, 78%, 90%, 89% and 91%, respectively. Indeed, the high likelihood ratio for a
      positive test result (4.5) and the low likelihood ratio for a negative test
      result (0.05) demonstrated the clinical utility of metabolic imaging in "ruling
      in" disease as well as "ruling out" recurrence. In conclusion, whole-body FDG PET
      appears useful in the post-therapy surveillance of endometrial cancers, both for
      the accurate localisation of suspected recurrences and for the detection of
      asymptomatic recurrent disease.

PMID- 12192558
TI  - Memory functions and rCBF (99m)Tc-HMPAO SPET: developing diagnostics in
      Alzheimer's disease.
AB  - Alzheimer's disease (AD) is a primary degenerative disease of the brain. The
      prevalence increases with age, with devastating consequences for the individual
      and society. The aim of this study was to evaluate whether patients with early AD
      show an altered regional cerebral blood flow (rCBF) compared with control
      persons. Furthermore, we aimed to investigate the correlation between rCBF in
      sublobar volumes of the brain and performance on memory tests. Memory tests were
      chosen to evaluate episodic and semantic memory. Fourteen patients (aged 75.2+/
      8.8 years) with early AD and 15 control persons (aged 71.4+/-3.2 years) were
      included. rCBF measurements with single-photon emission tomography (SPET) using
      technetium-99m hexamethylpropylene amine oxime (HMPAO) were performed. The rCBF
      (99m)Tc-HMPAO SPET images were spatially transformed to fit a brain atlas and
      normalised for differences in rCBF (Computerised Brain Atlas software). Cortical
      and subcortical volumes of interest (VOIs) were analysed and compared. Compared
      with the controls, AD patients showed a significantly lower rCBF ratio in
      temporoparietal regions, including the left hippocampus. The diagnostic
      sensitivity and specificity for AD were high in temporoparietal regions. AD
      patients had significantly reduced performance on semantic and, in particular,
      episodic memory tests compared with age-matched normative data, and their
      performance on several episodic tests correlated with rCBF ratios in parietal and
      temporal regions, including the left hippocampus. The correlation between rCBF
      ratio and level of episodic memory performance suggests that abnormalities in
      rCBF pattern underlie impaired episodic memory functioning in AD.

PMID- 12192559
TI  - Sarcoma tumor FDG uptake measured by PET and patient outcome: a retrospective
      analysis.
AB  - In a retrospective analysis of patients with sarcoma who underwent
      fluorodeoxyglucose positron emission tomography (FDG PET) imaging, tumor maximum
      FDG uptake was analyzed for ability to predict patient survival and disease-free
      interval. Two hundred and nine patients with sarcoma were imaged prior to
      treatment with neoadjuvant chemotherapy or resection. Tumor FDG uptake expressed
      as maximum standard uptake value (SUV(max)) was compared with disease-free and
      overall survival. A multivariate Cox regression analysis was applied to examine
      the role of SUV(max) in predicting time to death or disease progression, after
      adjusting for standard clinical prognostic factors. The multivariate analyses
      showed that the SUV(max) information is a statistically significant independent
      predictor of patient survival. Tumors with larger SUV(max) have a significantly
      poorer prognosis. This retrospective analysis indicates that the sarcoma tumor
      SUV(max) value determined by PET is an independent predictor of survival and
      disease progression.

PMID- 12192560
TI  - [(18)F]FDG in childhood lymphoma: clinical utility and impact on management.
AB  - Positron emission tomography (PET) with fluorine-18 fluorodeoxyglucose (FDG) is a
      very useful technique for the imaging of lymphomas in the adult population. It
      provides unique information about the behaviour of malignant cells and
      contributes to more accurate staging of the illness and better assessment of
      response to therapy. The purpose of this study was to evaluate the usefulness of
      FDG PET in childhood lymphoma compared with conventional imaging methods (CIMs)
      and clinical data. Between July 1998 and August 2001, 42 FDG PET examinations
      were performed using a dedicated PET system (27 examinations) or a hybrid
      coincidence PET system (15 examinations) for initial tumour staging ( n=7),
      restaging ( n=5) or assessment of response to therapy or residual masses ( n=30)
      in 27 children with Hodgkin's disease (HD) ( n=20) or non-Hodgkin's lymphoma
      (NHL) ( n=7). FDG PET results were compared with CIM findings and clinical data.
      Since 2000, a standardised questionnaire for evaluation of the clinical impact of
      FDG PET on both staging and therapy has been sent to the 16 referring physicians
      and 13 have replied. In all children, FDG PET was performed without any side
      effects. FDG PET was found to be very sensitive (Se=12/12) for staging and
      restaging of the illness, showing more lesions than CIMs, with a 50% patient
      upstaging rate (6/12). It was very accurate for monitoring response to therapy
      and for characterisation of residual masses. False-positive results were observed
      in two NHL patients with thymic uptake and one false-negative result was obtained
      in a patient whose NHL relapsed 1 month after a negative FDG PET. The
      questionnaire emphasised the impact of FDG PET on clinical management, which was
      modified on the basis of the FDG PET results in 23% of patients. As previously
      demonstrated in the adult population, FDG PET appeared to be a very sensitive
      imaging technique for staging and restaging of lymphoma in children and was very
      useful for monitoring the response to therapy.

PMID- 12192561
TI  - FDG-PET imaging in lung cancer: how sensitive is it for bronchioloalveolar
      carcinoma?
AB  - While characterization of lung lesions and staging of lung cancer with fluorine
      18 fluorodeoxyglucose positron emission tomography (FDG-PET) is an established
      clinical procedure, a lower diagnostic accuracy of FDG-PET for diagnosis and
      staging of so-called bronchioloalveolar carcinoma (BAC) has been reported.
      Therefore, the accuracy of PET for diagnosing and staging of BAC was
      investigated. We studied 41 patients eventually found to have adenocarcinoma with
      a bronchioloalveolar growth pattern who were referred for characterization or
      staging of lung lesions with whole-body FDG-PET between January 1998 and March
      2001: there were 11 males (27%) and 30 females (73%), with a mean age of 66.0+/
      10.9 (range =44-84 years). Patients were imaged using ECAT EXACT or HR+ systems.
      All patients had non-attenuation-corrected scans, while transmission data for
      attenuation correction were also available for 12 patients (29%). PET correctly
      identified BAC in 41 of the 46 (89%) lesions and 39 of the 41 patients (95%). By
      pathology, 25 patients (61%) were found to have unifocal or nodular lesions; this
      pattern was correctly identified by PET in 20 patients (80%) and by CT in 18
      (72%). PET correctly identified 7 (44%) of 16 patients (39%) who had multicentric
      or diffuse BAC, and CT identified 11 (69%). Of the 35 patients whose lymph node
      status was verified pathologically, PET was correct in 27 (77%) and CT in 24
      (69%). PET missed 67% of the rare tumors that had a pure BAC pattern with no
      invasive component. It is concluded that the diagnostic performance of whole-body
      FDG-PET is similar in most patients with lesions with a BAC pattern and in other
      non-small cell lung cancer types. PET is less accurate in patients with rare BAC
      tumors that have no invasive component.

PMID- 12192562
TI  - Evaluation of pyrimidine metabolising enzymes and in vitro uptake of 3'
      [(18)F]fluoro-3'-deoxythymidine ([(18)F]FLT) in pancreatic cancer cell lines.
AB  - Here we report the expression of major pyrimidine metabolising enzymes in
      pancreatic cancer cell lines, chronic pancreatitis tissue and human pancreatic
      cancer and the in vitro uptake of 3'-[(18)F]fluoro-3'-deoxythymidine
      ([(18)F]FLT). The expression of pyrimidine metabolising enzymes was evaluated
      with real-time PCR, Western blot and immunostaining. Thymidine kinase 1 (TK-1)
      activity was measured with a fluorocytometric assay. The cellular uptake and
      intracellular metabolism of [(18)F]FLT were evaluated in pancreatic lobules and
      in transformed cancer cell lines. TK-1 and thymidine synthetase mRNA were
      increased in six pancreatic cancer cell lines, while mRNA levels of thymidine
      kinase 2 and deoxycytidine kinase were down-regulated. High TK-1 activity was
      confirmed in all cell lines. Furthermore, TK-1 was overexpressed in human
      pancreatic cancer as compared with normal pancreatic tissue and samples from
      patients with chronic pancreatitis. The cellular uptake of [(18)F]FLT was 18.4%+/
      3.6% and 5.2%+/-1.4% of the applied radioactivity after 240 min in SW-979 and
      BxPc-3 cells, respectively, while uptake of [(18)F]fluorodeoxyglucose
      ([(18)F]FDG) was only 0.6%+/-0.04% (SW-979) and 0.3%+/-0.13% (BxPc-3) after 240
      min of incubation. In contrast, cellular uptake of [(18)F]FLT in isolated
      pancreatic lobules and growth-arrested HT1080 cells was lower as compared with
      the uptake of [(18)F]FDG and with the malignant pancreatic cancer cell lines.
      HPLC analysis of the perchloric acid-soluble cell fraction demonstrated the
      phosphorylation of [(18)F]FLT to the respective monophosphate in both cell lines.
      Furthermore, 0.8%+/-0.12% (BxPc-3) and 1.3%+/-0.38% (SW-979) of the applied
      radioactivity was detected in the perchloric acid-insoluble cell fraction,
      indicating the incorporation of [(18)F]FLT into the DNA. Our results demonstrate
      the cellular uptake, intracellular trapping and incorporation into the DNA of
      [(18)F]FLT in pancreatic cancer cells in vitro. TK-1, as the rate-limiting enzyme
      of [(18)F]FLT metabolism, is overexpressed in pancreatic cancer cell lines and in
      human pancreatic cancer. Thus, we propose [(18)F]FLT as a promising tracer for
      positron emission tomography that might overcome current limitations in the
      diagnosis of pancreatic cancer.

PMID- 12192563
TI  - Carbon-11 tyrosine PET for visualization and protein synthesis rate assessment of
      laryngeal and hypopharyngeal carcinomas.
AB  - Accurate assessment of tumour extent and lymph node involvement in squamous cell
      carcinomas of the head and neck region is essential for therapy planning.
      Unfortunately, conventional diagnostic examination and imaging techniques, which
      monitor tumours on the basis of anatomical parameters, have drawbacks in clinical
      practice. The aim of this study was to investigate the feasibility of L-[1-(11)C]
      tyrosine (TYR) positron emission tomography (PET) for visualisation of squamous
      cell carcinoma of the larynx and hypopharynx and quantification of tumour
      activity by assessment of protein synthesis rate (PSR). Dynamic TYR PET was
      performed on 31 patients with T1-T4 laryngeal or hypopharyngeal carcinoma before
      therapy. Plasma activity of TYR, (11)CO(2) and (11)C-protein levels were
      measured, and PSRs were calculated for primary malignancies. All 31 laryngeal and
      hypopharyngeal tumours were visualised as a hotspot (sensitivity 100%). The
      median PSR of the tumours (2.06 nmol ml(-1) min(-1); range 0.72-6.96) was
      significantly higher ( P<0.001) than that of non-tumour (background) tissue (0.51
      nmol ml(-1) min(-1); range 0.22-0.89). L-[1-(11)C]-Tyrosine PET appears to be a
      potential method for visualisation of primary laryngeal and hypopharyngeal
      tumours. In vivo quantification of tumour activity by assessment of PSR is
      possible and may have a future role in the therapy planning and therapy
      evaluation of laryngeal and hypopharyngeal tumours.

PMID- 12192564
TI  - Acquisition of linograms in SPET: implementation and benefits.
AB  - Compared with other tomographic modalities, single-photon emission tomography
      (SPET), the most widely used tomographic modality in nuclear medicine, suffers
      from poor quality image since the collimator stops 99.99% of the emitted gamma
      rays reaching the detector. This paper describes a new SPET acquisition modality
      using a very short focal length (12.5 cm) fan-beam collimator and a very short
      transverse field of view detector (25 cm). The detector moves along at least two
      linear orthogonal orbits in such a way that the focal line travels through the
      source target. This linear orbit acquisition (LOrA) generates linograms forming a
      complete set of tomographic data, i.e. sufficient to exactly reconstruct the
      activity map using a modified filtered back-projection algorithm. In contrast to
      the classical fan-beam tomography, truncation is not a problem, even when the
      source transverse size is much larger than the detector transverse size. When the
      collimator hole length/diameter ratio is adapted to obtain a spatial resolution
      similar to that of classical SPET, LOrA SPET offers an improvement in sensitivity
      by a factor of about 2.5 for a 20-cm source size. This improvement is achieved
      with a detector that is half as large, and thus half as expensive. As with
      classical fan-beam SPET, the sensitivity increases further if the target size
      decreases. When fitting the collimator to obtain a similar sensitivity to that of
      classical SPET, a significant improvement in spatial resolution is obtained.

PMID- 12192565
TI  - Preliminary experiences with sentinel lymph node detection in cases of vulvar
      malignancy.
AB  - Lymph node status is the most important prognostic factor in vulvar malignancy.
      The aim of this pilot study was to explore the clinical significance of
      radionuclide lymphoscintigraphy in the management of vulvar neoplasms. Eight
      patients with squamous cell carcinoma and two patients with malignant melanoma of
      the vulva were studied with 100 MBq technetium-99m nanocolloid (Sentiscint,
      OSSKI, Budapest) 1 day before surgery. The location of the sentinel lymph node
      was checked by a single-head gamma camera-computer system (MB 9200, Mediso,
      Budapest). Vulvectomy with bilateral inguinofemoral lymphadenectomy was performed
      in each case. At lymphadenectomy, the sentinel lymph node was separately removed
      and histologically studied. Three of the ten patients had positive sentinel lymph
      nodes (micrometastasis). Five months later one of them had local recurrence of
      the vulvar cancer, and another had inguinal recurrence of the tumour 6 months
      postoperatively; the third patient was operated on only recently. Our preliminary
      results are impressive and suggest that lymphoscintigraphy is an easy and
      reliable method for detection of the sentinel lymph node in vulvar malignancy.

PMID- 12192566
TI  - (99m)Tc-MIBI radio-guided surgery for recurrent thyroid carcinoma: technical
      feasibility and procedure, and preliminary clinical results.
AB  - The preliminary results of technetium-99m methoxyisobutylisonitrile (MIBI) radio
      guided surgery (RGS) in patients with differentiated thyroid carcinoma (DTC) and
      iodine-131-negative (non-functioning) recurrent disease are reported. Eight
      consecutive DTC patients were selected for RGS on the basis of pre-operative
      imaging findings: a (99m)Tc-MIBI scan consistent with local recurrence was taken
      as the principal inclusion criterion. The RGS procedure that we developed
      consisted in the injection of a low dose of (99m)Tc-MIBI (37 MBq) in the
      operating theatre a few minutes before the beginning of the intervention, with
      use of a hand-held gamma probe for the intra-operative detection of (99m)Tc-MIBI
      avid tumoural foci. Radioactivity was measured in tumoural foci both in vivo and
      ex vivo, in the background and in the tumoural bed after lesion extirpation.
      After follow-up for 2-10 months, stable normalisation of serum thyroglobulin (Tg)
      levels was observed in six out of the seven patients in whom, during the
      intervention, the gamma probe-detected radioactivity in the neck fell to
      background values after tumour extirpation. In another patient the persistence of
      high radioactivity levels in the tumoural bed after lesion removal correctly
      suggested disease persistence (deep tracheal infiltration). These preliminary
      data suggest the feasibility of RGS in DTC patients with locoregional non
      functioning but (99m)Tc-MIBI-avid recurrence by injection of a low, 37 MBq dose
      of (99m)Tc-MIBI just before the beginning of the intervention.

PMID- 12192567
TI  - Phase 1 study to identify tumour hypoxia in patients with head and neck cancer
      using technetium-99m BRU 59-21.
AB  - The aim of this study was to assess the safety and biodistribution of technetium
      99m BRU 59-21, a novel radioactively labelled 2-nitro-imidazole hypoxic marker,
      in head and neck cancer patients and to correlate uptake with pimonidazole
      staining. (99m)Tc-BRU 59-21 was administered intravenously (mean dose 824 MBq,
      range 780-857 MBq) to ten head and neck cancer patients scheduled for primary
      surgery, and whole-body images and SPET scans were then obtained. Uptake of
      radioactivity in the regions of interest was determined and tumour to normal
      tissue ratios were calculated after correlative evaluation with MRI/CT. Twelve to
      16 h before surgery (up to 2 weeks after the scan), patients received
      pimonidazole intravenously. Tumour sections were stained immunohistochemically
      for pimonidazole binding. No serious adverse events were reported. In five
      patients there were ten adverse events, which were mild in intensity and resolved
      completely without intervention. Uptake of (99m)Tc-BRU 59-21 was observed in
      eight of the ten primary tumours. Tumour to normal tissue ratios on the SPET
      scans for primary tumour and lymph nodes increased from 1.8 (range 0.9-2.7) to
      2.1 (range 0.8-3.7) between 30 min and 3 h post injection. Tumour to normal
      tissue ratios in the primary tumour were significantly correlated with
      pimonidazole staining for SPET scans performed 30 min and 3 h post injection (
      P=0.016 and P=0.037, respectively). When primary tumour and involved lymph nodes
      were considered in conjunction, correlation between the tumour to normal tissue
      ratio and pimonidazole staining was observed for early ( P<0.001) but not for
      late SPET scans ( P=0.076). However, late scans showed better tumour delineation
      than early scans. Administration of (99m)Tc-BRU 59-21 in head and neck cancer
      patients appears to be safe and feasible. Uptake and retention in tumour tissue
      was observed, suggestive of tumour hypoxia, and this was supported by
      correlations with staining for the hypoxic marker pimonidazole.

PMID- 12192568
TI  - Rolipram depresses [(3)H]2-deoxyglucose uptake in mouse brain and heart in vivo.
AB  - The effects of systemic administration of rolipram, a selective phosphodiesterase
      type 4 inhibitor, on [(3)H]2-deoxyglucose (DG) uptake in brain and peripheral
      tissues were examined. Rolipram significantly and dose-dependently decreased
      [(3)H]DG uptake in brain, heart and skeletal muscle. In contrast, the
      radioactivity concentrations in the plasma of rolipram-treated mice were
      significantly higher than those of control mice at all times after injection of
      the tracer. In the kinetic study, the initial uptake of [(3)H]DG in brain was
      decreased by rolipram, whereas no significant differences were observed in the
      uptake in heart and skeletal muscle. However, radioactivity concentrations in the
      brain, heart and skeletal muscle 30 min after the injection of [(3)H]DG were
      significantly lowered by rolipram to about 60%, 10% and 10% of control values,
      respectively. The uptake of [(13)N]ammonia in brain and heart of rolipram-treated
      mice was slightly decreased, which indicated that rolipram diminished both
      cerebral and cardiac blood flow. These results indicate that the phosphorylation
      process via hexokinase rather than the transport of [(3)H]DG might be depressed
      by rolipram. Together with the previous observations that inhibition of protein
      kinase A (PKA) markedly enhanced [(14)C]DG uptake in rat brain, these results
      indicate an important role of the cAMP/PKA systems in the regulation of glucose
      metabolism in the living brain as well as in peripheral tissues such as the heart
      and skeletal muscle.

PMID- 12192569
TI  - The potential of the beta-Microprobe, an intracerebral radiosensitive probe, to
      monitor the [(18)F]MPPF binding in the rat dorsal raphe nucleus.
AB  - The aim of this study was to demonstrate the ability of a recently developed
      beta(+)-range sensitive intracerebral probe (beta-Microprobe) to measure the
      binding kinetics of [(18)F]MPPF, a well-documented 5-HT(1A) serotoninergic
      receptor ligand, in the dorsal raphe nucleus (DRN) of the anaesthetised rat. This
      midbrain nucleus presents a high concentration of 5-HT(1A) receptors known to be
      implicated in the effects of antidepressants. The difficulty confronting this
      study lay in the fact that the dimensions of the DRN are smaller than the
      detection volume of the beta-Microprobe. In the first part of the study, we
      studied the feasibility of this measurement from a theoretical point of view by
      autoradiography and a Monte Carlo simulation. We determined the optimal beta
      Microprobe location close to the DRN and verified that this configuration allowed
      accurate determination of [(18)F]MPPF specific binding in the nucleus. In the
      second part of our study, we measured the in vivo time-concentration curves of
      [(18)F]MPPF binding in the DRN in comparison with the cerebellum. The specificity
      of [(18)F]MPPF binding in the DRN was confirmed by its displacement after non
      labelled 5-HT(1A)antagonist injection (MPPF or WAY-100635). Moreover, we verified
      the feasibility of using beta-Microprobe monitoring and simultaneous validation
      by microdialysis to study the effect of an increase in extracellular serotonin,
      induced by fenfluramine injection, on [(18)F]MPPF binding in the DRN. Our
      theoretical simulations, confirmed by our experimental results, demonstrate the
      ability of this new device to monitor in vivo the binding of [(18)F]MPPF in the
      DRN of anaesthetised rodents.

PMID- 12192570
TI  - The need for standardisation of cardiac FDG PET imaging in the evaluation of
      myocardial viability in patients with chronic ischaemic left ventricular
      dysfunction.
AB  - The evaluation of myocardial glucose utilisation with fluorine-18
      fluorodeoxyglucose (FDG) and positron emission tomography is currently considered
      the most reliable tool for the identification of myocardial viability. However,
      the investigations using FDG imaging to predict improvement in left ventricular
      (LV) function after revascularisation have reported wide ranges for sensitivity
      (71%-100%) and, in particular, for specificity (33%-91%). The variable results
      may be related to differences in study populations but also to differences in the
      imaging protocols employed. Detailed analysis of the published studies has
      revealed differences in study populations, patient selection criteria, the
      methods for assessing changes in LV function post revascularisation and the
      timing of these assessments. Even more importantly, protocols have varied
      substantially with regard to imaging equipment, perfusion tracers, metabolic
      conditions, data analysis and interpretation of results. In addition, evaluation
      of patients with insulin resistance appears to represent a specific challenge.
      This review examines the different study protocols and methodologies used for
      myocardial FDG imaging in order to draw conclusions concerning optimal imaging
      protocols. It appears that the optimisation and standardisation of study
      protocols and analysis of FDG images for the assessment of myocardial viability
      are critical. In addition, multi-centre trials seem warranted on prediction of
      long-term function, congestive heart failure symptoms, survival and quality of
      life.

PMID- 12192573
TI  - Commonalities and differences in control of various drawing movements.
AB  - Characteristics of control at the shoulder and elbow during nine types of drawing
      movements were studied in the present work. The task was to repetitively track a
      template, depicted on a horizontal table, with the index finger at a cyclic
      frequency of 1.5 Hz. The templates were a circle, four ovals and four lines of
      different orientations. The wrist was immobilized and the movement consisted of
      rotations at the shoulder and elbow joints. The studied movements varied in a
      wide range with respect to the amplitude of elbow and shoulder movements and
      relative phase between them. Kinetic analysis included analysis of torque signs,
      impulses, and timing. It demonstrated that the role of muscle torque in movement
      production was different at the two joints. During eight out of the nine movement
      types, the muscle torque at the shoulder accelerated and decelerated this joint
      and almost completely coped with the influence of the interactive torque arising
      from elbow motion. Conversely, interactive torque generated by shoulder motion
      played a dominant role in elbow acceleration and deceleration, whereas muscle
      torque at the elbow adjusted passive elbow movement to the various template
      shapes. EMG data were in agreement with the conclusions made from the kinetic
      analysis. Collectively, these data support the hypothesis that the two joints
      have different functions in movement production. The shoulder creates a
      foundation for motion of the entire arm through the interactive torque, and the
      elbow serves as a fine-tuner of the end-point movement. Control of the shoulder
      was similar across the eight movement types and the differences in the end-point
      path were provided by variations in elbow control. The two joints exchanged roles
      during one movement type, namely, drawing the line tilted right. During this
      movement, the elbow musculature generated motion at this joint and the shoulder
      musculature counteracted mechanical influence of this motion on the shoulder
      position. The findings suggest that during drawing movements, the control
      strategy exploits intersegmental dynamics of the shoulder-elbow mechanical
      linkage.

PMID- 12192572
TI  - Cognitive mechanisms of transitive inference.
AB  - We examined how the brain organizes interrelated facts during learning and how
      the facts are subsequently manipulated in a transitive inference (TI) paradigm
      (e.g., if A<B and B<C, then A<C). This task determined features such as learned
      facts and behavioral goals, but the learned facts could be organized in any of
      several ways. For example, if one learns a list by operating on paired items, the
      pairs may be stored individually as separate facts and reaction time (RT) should
      decrease with learning. Alternatively, the pairs may be stored as a single,
      unified list, which may yield a different RT pattern. We characterized RT
      patterns that occurred as participants learned, by trial and error, the
      predetermined order of 11 shapes. The task goal was to choose the shape occurring
      closer to the end of the list, and feedback about correctness was provided during
      this phase. RT increased even as its variance decreased during learning,
      suggesting that the learnt knowledge became progressively unified into a single
      representation, requiring more time to manipulate as participants acquired
      relational knowledge. After learning, non-adjacent (NA) list items were presented
      to examine how participants reasoned in a TI task. The task goal also required
      choosing from each presented pair the item occurring closer to the list end, but
      without feedback. Participants could solve the TI problems by applying formal
      logic to the previously learnt pairs of adjacent items; alternatively, they could
      manipulate a single, unified representation of the list. Shorter RT occurred for
      NA pairs having more intervening items, supporting the hypothesis that humans
      employ unified mental representations during TI. The response pattern does not
      support mental logic solutions of applying inference rules sequentially, which
      would predict longer RT with more intervening items. We conclude that the brain
      organizes information in such a way that reflects the relations among the items,
      even if the facts were learned in an arbitrary order, and that this
      representation is subsequently used to make inferences.

PMID- 12192574
TI  - Adaptations in arm movements for added mass to wrist or ankle during walking.
AB  - The aim of the present study was to answer the question whether adaptations to
      local perturbations are restricted to the perturbed limb or whether they induce a
      reorganization of all co-moving limbs. Specifically, we studied the adaptations
      in arm movements to mass perturbations in seven healthy adults during walking on
      a treadmill. Four different perturbation conditions were employed in random order
      (no perturbation, mass added to both wrists, to the right wrist, and to the right
      ankle). During each experimental condition ten different belt speeds (0.5, 1.0,
      1.5, 2.0, 2.5, 3.0, 3.5, 4.0, 4.5, 5.0 km/h) were successively offered, while the
      arm movements and the electromyographic activity of the musculus deltoid
      posterior and anterior were measured. The results indicated that cadence was not
      affected by adding mass to the wrist or ankle. However, adding mass to a wrist
      not only resulted in an increase in muscle activity and a decrease of movement
      amplitude of the perturbed arm, but also in alterations in the non-perturbed arm.
      Notably, adding mass to one ankle induced adaptive changes in both arms, in that
      both muscle activity and arm movement increased. The present results indicate
      that during walking the loading of one of the limbs induces a general
      reorganization, involving all participating bodily segments, presumably to
      maintain balance while providing rhythm constancy.

PMID- 12192575
TI  - Haptic discrimination of stimuli varying in amplitude and width.
AB  - We studied active haptic discrimination of the geometrical features of an object.
      The geometrical parameters under investigation were the amplitude and width of a
      gaussian-shaped surface. Haptic discrimination thresholds were measured with
      regard to three values of these geometrical parameters. We found that humans
      discriminate up to about 300 shapes when both amplitude and width are
      extrapolated to the range between 1 micro m and 1 m. Over this range, which
      covers the span of the arms, the number of discriminations is small compared to
      the number across the full range of chromaticities in vision. Roughly speaking,
      humans are far better at discriminating sharp (extensive amplitude and little
      width) gaussian surfaces from smooth (small amplitude and extensive width) ones
      than they are at discriminating small (small amplitude and width) surfaces from
      large (extensive amplitude and width) ones. Our main conclusion is that
      discrimination in the geometrical domain is poorest when the proportion between
      amplitude and width is roughly the same for both shapes. Our results are in close
      agreement with results of earlier experiments on detection thresholds. This
      indicates that similar, or even the same, neural mechanisms were used for
      detection and discrimination of the geometrical parameters under investigation.

PMID- 12192576
TI  - Environmental constraints on foot trajectory reveal the capacity for modulation
      of anticipatory postural adjustments during rapid triggered stepping reactions.
AB  - This study used environmental restrictions on foot movement to challenge the
      capacity of the central nervous system (CNS) to counter the lateral instability
      that arises after foot-lift during rapid triggered stepping reactions evoked by
      unpredictable postural perturbation. The objective was to determine the extent to
      which lateral stability could be regulated via modulation of the mediolateral (m
      l) anticipatory postural adjustment (APA) that precedes foot-lift. A high frontal
      obstacle was used to double the required swing duration, and thereby increase the
      potential for the center of mass (COM) to fall laterally toward the unsupported
      side, during forward-step reactions. The capacity to use lateral step placement
      to recover lateral stability was restricted by means of lateral barriers. Six
      healthy young adults were tested. In obstacle-only trials, the APA was
      insufficient to prevent increased lateral COM motion during the prolonged swing
      phase; hence, lateral step placement was necessitated. However, when lateral
      stepping was obstructed, the CNS was able to upregulate the APA amplitude so as
      to prevent this increase in lateral COM motion. The swing foot was placed
      medially, with no detriment to clearing the frontal obstacle or recovering
      equilibrium. There was no change in step timing or anteroposterior (a-p) COM
      motion. While previous studies have suggested that the a-p COM progression may
      determine the extent to which the m-l APA is expressed or truncated during
      triggered stepping reactions evoked by unpredictable perturbation, the present
      findings demonstrate that prior knowledge of environmental demands can lead to
      predictive efforts to modulate the APA during such reactions. An apparent
      preference to underscale anticipatory efforts when lateral step placement is
      permitted suggests that the CNS may be acting to avoid some potential risk or
      cost associated with the execution of a large APA.

PMID- 12192577
TI  - Changes in cutaneomuscular reflex responses in relation to normal ageing in man.
AB  - Changes in cutaneomuscular reflex responses (CMRs) have been studied in relation
      to normal ageing in man. Multiunit surface EMG signals were recorded from right
      and left first dorsal interosseous (1DI) hand muscles from 23 elderly adults
      (mean age 71.1, range 58-88 years) and 11 young adults (mean age 25.9, range 19
      31 years). Subjects (1) performed index finger abduction and (2) gripped a dowel
      while concomitant stimulation of the digital nerves of the index finger was
      delivered at x2.5 threshold for perception. The E1 spinally mediated components
      of the CMRs recorded from 1DI were significantly smaller in the elderly subjects
      compared with young subjects for both tasks. The I1 and E2 transcortical
      components did not show a significant change in size with age although the
      incidence of I1 components was significantly reduced in the elderly subjects.

PMID- 12192578
TI  - Tactile inhibition of return: non-ocular response inhibition and mode of
      response.
AB  - Inhibition of return (IOR) refers to the slowing of responses to stimuli
      presented at the same location as a preceding cue. However, the cue-target
      paradigm used in most previous studies may have overestimated the contribution of
      eye movement programming to IOR, due to the existence of manual response
      inhibition effects. This confound can be circumvented by using a target-target
      paradigm in which participants respond to all stimuli. Here, we compared IOR
      magnitude from tactile cue-target and target-target tasks involving identical
      interstimulus intervals of 1,400 and 1,800 ms. Reaction times were measured using
      a foot pedal toe-lift response and a vocal response. Tactile IOR was observed
      using both modes of response, demonstrating IOR for the first time using a non
      spatial, vocal response. Moreover, IOR effects were significantly smaller in
      target-target compared to cue-target conditions, thereby confirming the existence
      of the response inhibition confound.

PMID- 12192579
TI  - Effects of body lean and visual information on the equilibrium maintenance during
      stance.
AB  - Maintenance of equilibrium was tested in conditions when humans assume different
      leaning postures during upright standing. Subjects ( n=11) stood in 13 different
      body postures specified by visual center of pressure (COP) targets within their
      base of support (BOS). Different types of visual information were tested:
      continuous presentation of visual target, no vision after target presentation,
      and with simultaneous visual feedback of the COP. The following variables were
      used to describe the equilibrium maintenance: the mean of the COP position, the
      area of the ellipse covering the COP sway, and the resultant median frequency of
      the power spectral density of the COP displacement. The variability of the COP
      displacement, quantified by the COP area variable, increased when subjects
      occupied leaning postures, irrespective of the kind of visual information
      provided. This variability also increased when vision was removed in relation to
      when vision was present. Without vision, drifts in the COP data were observed
      which were larger for COP targets farther away from the neutral position. When
      COP feedback was given in addition to the visual target, the postural control
      system did not control stance better than in the condition with only visual
      information. These results indicate that the visual information is used by the
      postural control system at both short and long time scales.

PMID- 12192580
TI  - Spatiotemporal consistency of human mandibular and head-neck movement
      trajectories during jaw opening-closing tasks.
AB  - Previous studies of spatial and temporal coordination between human mandibular
      and head-neck movements during single as well as rhythmic jaw opening-closing
      tasks suggest that these movements are regulated by central nervous commands
      common for jaw and neck muscles. The present study evaluated the spatiotemporal
      consistency of concomitant mandibular and head-neck movements during repeated
      single jaw opening-closing tasks, in short- as well as long-term perspectives and
      at different speeds. The subjects were seated in an upright position without head
      support. They were instructed to perform single maximal jaw opening-closing
      movements, repeated ten times for fast and slow speed, respectively. Recordings
      were made at two sessions. A wireless optoelectronic technique was used to record
      three-dimensional mandibular and head-neck movements. The spatiotemporal
      consistency of repeated movement trajectories of the mandible (both in relation
      to the head and in space) and of the head-neck was quantitatively assessed by a
      spatiotemporal index (STI). In addition, mean movement trajectory patterns were
      compared for speed and recording sessions (expressed as correlation coefficient,
      r). The results showed relatively small STI (high degree of spatiotemporal
      consistency) and high r (reproducible trajectory patterns) values, both in short-
      and long-term perspectives, for concomitant mandibular and head-neck movements.
      The data were not generally speed related. In conclusion, the present results
      suggest a high degree of spatiotemporal consistency of the kinematic patterns of
      mandibular and head-neck movements during jaw opening-closing, in short- as well
      as long-term perspectives. They also indicate that underlying neural processes
      are invariant in nature. The results give further support to the notion of a
      tight functional coupling between the human jaw and the neck motor systems during
      natural jaw function.

PMID- 12192582
TI  - Neural mechanisms involved in the functional linking of motor cortical points.
AB  - We sought to understand the basic neural processes involved in the functional
      linking of motor cortical points. We asked which of the two basic neural
      mechanisms, excitation or inhibition, is required to functionally link motor
      cortical points. In the ketamine-anaesthetized cat, a microstimulation electrode
      was positioned at a point (control point) that was identified by the following
      three characteristics of the EMG responses: the muscle(s) activated at threshold,
      any additional muscles recruited by supra-threshold stimulation, and their
      relative latency. A second distinct point (test point) producing activation of a
      muscle at a different joint was then identified. At this test cortical point the
      GABA(A) receptor antagonist bicuculline was ejected iontophoretically, while
      stimulating the control point near threshold. A combined response was elicited
      consisting of the response normally elicited at the control point plus that
      elicited at the test point. Thus, an artificial muscle synergy was produced
      following disinhibition of the test point. This was never the case when glutamate
      was ejected at the test point, even when supra-threshold stimuli were used at the
      control point. Therefore, simply increasing the excitability of a cortical point
      was not sufficient to release the muscle(s) represented at that point into a
      muscle synergy. Kynurenate, a broadly acting excitatory amino acid receptor
      antagonist, ejected at the bicuculline point reversed the effect of bicuculline.
      This shows that the release phenomenon was mediated synaptically and was not due
      to spread of the stimulating current. We suggest that release from inhibition may
      be one of the neural mechanisms involved in functionally linking motor cortical
      points. This functional linking may be part of the ensemble of motor cortical
      mechanisms involved in recruitment of muscle synergies.

PMID- 12192581
TI  - Long-lasting potentiation effects induced in rats by kindling with an inverse
      agonist of the benzodiazepine receptor.
AB  - The present work analyzed the changes in evoked field potentials of freely moving
      rats after kindling induced by a convulsant inverse agonist of the GABA(A)
      benzodiazepine receptor complex, methyl beta-carboline-3-carboxylate (beta-CCM).
      Two doses of beta-CCM (2 mg/kg and 4 mg/kg) were used. In kindled and control
      animals, a stimulating electrode was implanted in the perforant pathway and a
      recording electrode in the dentate gyrus. Results showed that, after an acutely
      injected dose of 20 mg/kg pentylenetetrazol (PTZ), all kindled animals showed a
      decrease in population spike amplitude after 20 min. After 60 min, only fully
      kindled rats showed a long-lasting potentiation, also visible up to 24 h later,
      as compared to controls or nonkindled animals. Changes in glutamate and GABA
      receptor binding measured in previous experiments may explain this potentiation
      effect observed in fully kindled rats.

PMID- 12192583
TI  - Time courses of progress to the chronic stage of middle cerebral artery occlusion
      models in rats.
AB  - Several kinds of middle cerebral artery occlusion model in rats have been
      developed. Variable ischemic inductions are attributed to the different
      contributing factors in ischemic damage formation. In the present study, we
      examined the differences in ischemic induction attributed to chronic stage. Male
      Sprague-Dawley rats were subjected to two kinds of middle cerebral artery
      occlusion model, a thermocoagulation and a photothrombosis model. We compared the
      changes in body weight, neurological outcome, size of ischemic damage, brain
      edema and atrophy formation, and histological data for 84 days between a
      thermocoagulation and a photothrombosis model in rats. Although the time courses
      of infarction formation were no different, there were differences in the time
      courses of brain edema, atrophy formation, and neuronal deficits between the
      models. Microinfarction formation was observed as a characteristic of the
      photothrombosis model. The present study demonstrated that differences in
      ischemic induction did not affect maturation of infarct size, brain atrophy, or
      neuronal deficits 84 days after ischemia. However, the progress of maturation was
      different between the models. The possibility that reperfusion contributed to the
      time course of brain edema and atrophy was considered, and it was suggested that
      brain edema formation influenced neurological outcome.

PMID- 12192584
TI  - Photolytic flash-induced intercellular calcium waves using caged calcium
      ionophore in cultured astrocytes from newborn rats.
AB  - Waves of elevated intracellular free calcium that propagate between neighboring
      astrocytes are important for the intercellular communication between astrocytes
      as well as between neurons and astrocytes. However, the mechanisms responsible
      for the initiation and propagation of astrocytic calcium waves remain unclear. In
      this study, intercellular calcium waves were evoked by focal photolysis of a
      caged calcium ionophore (DMNPE-caged Br A23187) in cultured astrocytes from
      newborn rats. The focal photolysis of the caged compound resulted in the increase
      in intracellular calcium in a single astrocyte, and this increase then propagated
      to neighboring astrocytes. We also analyzed the spatiotemporal characteristics of
      the intercellular calcium waves, and estimated the propagation pathways for them.
      The method using a caged calcium ionophore described in this study provides a new
      in vitro model for the analysis of intercellular calcium waves.

PMID- 12192585
TI  - Cerebellar stimulation modulates the intensity of a visceral nociceptive reflex
      in the rat.
AB  - The cerebellum modulates different nociceptive phenomena and influences visceral
      functions. This study shows cerebellar modulation of an abdominal reflex elicited
      by a visceral noxious stimulus (colorectal distension, CRD). The intensity of the
      reflex was measured by electromyographic (EMG) recording from the rectus
      abdominus muscle, and the cerebellar cortex (vermis, lobule VIII), the fastigial
      nucleus, or the dentate nucleus was stimulated using D, L-homocysteic acid (0.1
      M, 1 micro l). To release the fastigial nucleus from inhibition by the Purkinje
      cells, bicuculline (GABA(A) receptor antagonist, 100 micro M, 1 micro l) was
      used. Stimulation of the cerebellar cortex enhanced, whereas stimulation or
      disinhibition of the fastigial nucleus decreased, the responses to CRD measured
      by EMG. Stimulation of the dentate nucleus did not have an obvious effect on the
      intensity of the reflex. These results are in agreement with the hypothesis that
      the cerebellum modulates visceral nociceptive functions, whereby the cerebellar
      cortex and the fastigial nucleus, respectively, play a pro-nociceptive and an
      anti-nociceptive role.

PMID- 12192586
TI  - Differential activation of monkey striatal neurons in the early and late stages
      of procedural learning.
AB  - The basal ganglia is a key structure for procedural learning. To examine in what
      aspects of procedural learning the basal ganglia participate, we recorded from
      striatal neurons (phasically active neurons) in monkeys while the animals were
      performing a sequential button press task (the 2 x 5 task) and compared the
      neuronal activity between two conditions: (1) while learning new sequences and
      (2) while executing overlearned sequences. Among 147 neurons recorded in two
      monkeys, 45 neurons were activated preferentially for new sequences (new
      preferring neurons), 34 for overlearned sequences (learned-preferring neurons),
      and 68 were activated non-selectively (non-selective neurons). New-preferring
      neurons were more abundant in the "association" region [association striatum
      (AS); caudate nucleus and rostral putamen anterior to the anterior commissure],
      while the learned-preferring neurons were more abundant in the "sensorimotor"
      region [sensorimotor striatum (SM); putamen posterior to the anterior
      commissure]. In addition to the learning dependency, the AS and SM neurons were
      activated in different task periods: many AS neurons were activated during the
      delay period, while the SM neurons were more activated with reaching and button
      presses. These data, together with the data from our previous blockade study,
      suggest that the "association" and "sensorimotor" regions of the basal ganglia
      contribute preferentially to the early and late stages of procedural learning,
      respectively.

PMID- 12192588
TI  - Proteomics without polyacrylamide: qualitative and quantitative uses of tandem
      mass spectrometry in proteome analysis.
AB  - Proteomics can be thought of as an attempt to understand the information encoded
      in genomic sequences from the perspective of proteins; i.e. the structure,
      function and regulation of biological processes at the protein level. In practice
      it stands in stark contrast to the hypothesis-driven serial approach practiced in
      the last century that was so successful for protein chemists and is built on the
      basic understanding of protein physicochemical properties developed during that
      era. Proteomics attempts to study biological processes comprehensively or
      globally by systematic parallel analysis of proteins expressed in a cell. While
      there are many analytical techniques in use and under development in proteomics,
      mass spectrometry is currently one of the field's most important discovery-based
      tools. This article will review some of the current approaches for qualitative
      and quantitative uses of tandem mass spectrometry in the field of proteomics
      specifically avoiding a discussion of the use of gel electrophoresis prior to
      mass spectrometry.

PMID- 12192589
TI  - Phylogenetic classification of transporters and other membrane proteins from
      Saccharomyces cerevisiae.
AB  - On the basis of functional and phylogenetic criteria, we have identified a total
      of 229 subfamilies and 111 singletons predicted to carry out transport or other
      membrane functions in Saccharomyces cerevisiae. We have extended the Transporter
      Classification (TC) and created a Membrane Classification (MC) for non
      transporter membrane proteins. Using the preliminary phylogenetic digits X, Y, Z
      (for new families, subfamilies, and clusters, respectively), we allocated a five
      digit number to 850 proteins predicted to contain more than two transmembrane
      domains. Compared with a previous TC of the yeast genome, we classified an
      additional set of 538 membrane proteins (transporters and non-transporters) and
      identified 111 novel phylogenetic subfamilies.

PMID- 12192590
TI  - Global analysis of gene expression in yeast.
AB  - In the past decade, there has been an intense effort to comprehensively catalogue
      the expressed genes in the yeast Saccharomyces cerevisiae and to determine the
      absolute and relative abundance of transcript and protein levels under different
      cellular conditions. Several methods have been developed to monitor gene
      expression: DNA microarray analysis, Serial Analysis of Gene Expression (SAGE),
      kinetic RT-PCR and monitoring expression of beta-galactosidase fusion proteins.
      These techniques have been used to measure transcript and protein abundance in
      different developmental states and under different environmental stimuli. A
      wealth of expression data for yeast is now publicly available through several web
      sites. The expression information that exists has the obvious benefits of
      providing a better understanding of the gene expression patterns that accompany
      changes in a yeast cell's environmental and developmental states. This data has
      also, however, provided clues to unraveling the complicated questions surrounding
      gene regulation: why and how is gene expression controlled?

PMID- 12192591
TI  - The genomics of yeast responses to environmental stress and starvation.
AB  - Unicellular organisms such as yeast have evolved to survive constant fluctuations
      in their external surroundings by rapidly adapting their internal systems to meet
      the challenges of each new environment. One aspect of this cellular adaptation is
      the reorganization of genomic expression to the program required for growth in
      each environment. The reprogramming of genomic expression can be unveiled using
      DNA microarrays, which measure the relative transcript abundance of essentially
      every gene in an organism's genome. Characterizing environmentally triggered gene
      expression changes provides insights into when, where, and how each gene is
      expressed and offers a glimpse at the physiological response of the cells to
      changes in their surroundings. This review will focus on the genomic expression
      responses of the budding yeast Saccharomyces cerevisiae to diverse environmental
      changes, highlighting some of the themes that have emerged from the collection of
      published yeast genomic expression studies. The results of these studies present
      insights as to how yeast cells sense and respond to each new environment, and
      suggest mechanisms that this organism uses to survive stressful environmental
      changes.

PMID- 12192592
TI  - Large-scale mutagenesis and functional genomics in yeast.
AB  - One of the major goals for the post-genome era is determining of the function of
      proteins predicted in the genome sequence. In many organisms functional
      assignments have been the results of comparative sequencing, proteomics or
      expression profiling. In the yeast, Saccharomyces cerevisiae, however, the
      functional role of a gene can be tested directly by disrupting the gene and
      examining the phenotype of the mutant. Because precise targeted deletions can be
      easily constructed, it is also possible to systematically delete every gene in
      the genome. Here we describe recent progress in yeast genome-wide mutagenesis
      programs and the results produced from analyzing the mutants created by them.

PMID- 12192593
TI  - Yeast and drug discovery.
AB  - Advanced genetic techniques, along with the high degree of conservation of basic
      cellular processes, have made the yeast Saccharomyces cerevisiae a valuable
      system for identification of new drug targets, target-based and non-target-based
      drug screening, and detailed analysis of the cellular effects of drugs. Yeast
      also presents a convenient system for antifungal drug discovery because it is
      closely related to Candida albicans, a major human pathogen. Many yeast genes
      remain poorly characterized, and most of the sophisticated techniques in yeast
      have been in widespread use less than a decade - a period shorter than the
      typical cycle from target identification to marketing approval for a new drug. It
      is likely that most of the benefits of yeast in discovery and development of
      therapeutic compounds have yet to be realized.

PMID- 12192594
TI  - Yeast genomic databases and the challenge of the post-genomic era.
AB  - Since the completion of the yeast genome sequence in 1996, three genomic
      databases, the Saccharomyces Genome Database, the Yeast Proteome Database, and
      MIPS (produced by the Munich Information Center for Protein Sequences), have
      organized published knowledge of yeast genes and proteins onto the framework of
      the genome. Now, post-genomic technologies are producing large-scale datasets of
      many types, and these pose new challenges for knowledge integration. This review
      first examines the structure and content of the three genomic databases, and then
      draws from them and other resources to examine the ways knowledge from the
      literature, genome, and post-genomic experiments is stored, integrated, and
      disseminated. To better understand the impact of post-genomic technologies, 20
      collections of post-genomic data were analyzed relative to a set of 243
      previously uncharacterized genes. The results indicate that post-genomic
      technologies are providing rich new information for nearly all yeast genes, but
      data from these experiments is scattered across many Web sites and the results
      from these experiments are poorly integrated with other forms of yeast knowledge.
      Goals for the next generation of databases are set forth which could lead to
      better access to yeast knowledge for yeast researchers and the entire scientific
      community.

PMID- 12192595
TI  - Suppression of tumor recurrence and metastasis by a combination of the PHSCN
      sequence and the antiangiogenic compound tetrathiomolybdate in prostate
      carcinoma.
AB  - Plasma fibronectin-mediated invasion of human DU145 prostate cancer cell line was
      efficaciously inhibited in a rat tumor model by treatment with Ac-PHSCN-NH(2)
      peptide. Invasion of DU145 cells was stimulated by the PHSRN sequence of plasma
      fibronectin. However, PHSCN acts as a competitive inhibitor of PHSRN-mediated
      invasion. In the current study, we determined whether PHSCN could inhibit the
      recurrence and metastasis of DU145 tumors after excision of the primary tumor in
      an athymic nude mouse model. We demonstrated that mice treated thrice weekly with
      intravenous Ac-PHSCN-NH(2) peptide survived tumor-free for more than 30 weeks
      post-primary tumor excision, whereas their untreated counterparts succumbed to
      recurrence and/or metastatic disease in significantly less time. Because of the
      universal requirement for angiogenesis in solid tumor growth, we tested the
      efficacy of copper deficiency induced by tetrathiomolybdate (TM) to retard tumor
      growth in the Dunning prostate cancer model. Significant reduction in size of the
      primary tumor was observed in mice rendered copper deficient. We sought to reduce
      tumor growth at the primary and metastatic sites by combining the anti-invasion
      Ac-PHSCN-NH(2) peptide with TM. Improved survival, fewer metastatic lesions, and
      excellent tolerability were observed with the combination therapy.

PMID- 12192596
TI  - Functional inactivation of pRB results in aneuploid mammalian cells after release
      from a mitotic block.
AB  - The widespread chromosome instability observed in tumors and in early stage
      carcinomas suggests that aneuploidy could be a prerequisite for cellular
      transformation and tumor initiation. Defects in tumor suppressors and genes that
      are part of mitotic checkpoints are likely candidates for the aneuploid
      phenotype. By using flow cytometric, cytogenetic, and immunocytochemistry
      techniques we investigated whether pRB deficiency could drive perpetual
      aneuploidy in normal human and mouse fibroblasts after mitotic checkpoint
      challenge by microtubule-destabilizing drugs. Both mouse and human pRB-deficient
      primary fibroblasts resulted, upon release from a mitotic block, in proliferating
      aneuploid cells possessing supernumerary centrosomes. Aneuploid pRB-deficient
      cells show an elevated variation in chromosome numbers among cells of the same
      clone. In addition, these cells acquired the capability to grow in an anchorage
      independent way at the same extent as tumor cells did suggesting aneuploidy as an
      initial mutational step in cell transformation. Normal Mouse Embryonic
      Fibroblasts (MEFs) harboring LoxP sites flanking exon 19 of the Rb gene arrested
      in G2/M with duplicated centrosomes after colcemid treatment. However, these
      cells escaped the arrest and became aneuploid upon pRB ablation by CRE
      recombinase, suggesting pRB as a major component of a checkpoint that controls
      cellular ploidy.

PMID- 12192597
TI  - IL-13Ralpha2 is a glioma-restricted receptor for interleukin-13.
AB  - We have found that binding sites for interleukin-13 (IL-13) are overexpressed in
      a vast majority of high-grade astrocytomas (HGAs). These binding sites for IL-13
      are distinct from the physiological receptor in that it does not bind IL-4. We
      also demonstrated that IL-13 receptor alpha 2 protein chain (IL-13Ralpha2), an IL
      4-independent receptor for IL-13, is abundant among HGAs, but not in normal
      organs. To examine if IL-13Ralpha2 is the tumor-associated site for IL-13, we
      stably transfected normal Chinese hamster ovary (CHO) cells and glioma G-26 cells
      to express either human (h) or murine (m) IL-13Ralpha2. CHO-hIL-13Ralpha2(+)
      cells and G-26-h/mIL-13Ralpha2(+) cells, and not CHO and G-26 parental or mock
      transfected cells, specifically bound IL-13 in an IL-4-independent manner. The IL
      13Ralpha2(+) cells also became highly susceptible to the killing by an IL-13
      based cytotoxic fusion protein. In loss of function studies, a HGA cell line, SNB
      19, was transfected with antisense (as) hIL-13Ralpha2. as-SNB-19-hIL-13Ralpha2(+)
      cells lost their natural affinity towards IL-13 and became resistant to IL-13
      based cytotoxins. The fact, that IL-13Ralpha2-positive cells bind IL-13
      independent of IL-4, become susceptible to IL-13 cytotoxins, and cells deprived
      of IL-13Ralpha2 receptor lose these features, demonstrates that IL-13Ralpha2 is
      the brain tumor-associated receptor for IL-13.

PMID- 12192598
TI  - Effect of insulin-like growth factor II on protecting myoblast cells against
      cisplatin-induced apoptosis through p70 S6 kinase pathway.
AB  - Insulin-like growth factor (IGF-II) is overexpressed in a variety of human tumors
      and has both mitogenic and antiapoptotic activity. Although the mechanisms of IGF
      II-induced proliferation have been well studied, the mechanisms underlying its
      survival signaling have been less well characterized. In this report, we
      investigated the role of IGF-II on cisplatin-induced apoptosis. We found that IGF
      II overexpression was associated with an increase in p70 ribosomal protein S6
      kinase (p70 S6K). Cisplatin treatment of C2C12 mouse myoblasts led to cell death
      associated with an inhibition of p70 S6K activity. Endogenous or exogenous IGF-II
      addition to C2C12 cells caused protection to cisplatin-induced apoptosis. This
      protection was associated in both cases with an increase in p70 S6K basal
      activity as well as resistance to cisplatin-induced decreased activity. Blockade
      of p70 S6K activation by rapamycin abrogated the IGF-II-mediated protection of
      cells to cisplatin-induced apoptosis. Furthermore, treatment of IGF-II
      overexpressing Rh30 and CTR rhabdomyosarcoma cells with rapamycin restored
      sensitivity to cisplatin-induced apoptosis. These data together suggest that IGF
      II-associated protection to cisplatin-induced apoptosis is mediated through an
      activation of the p70 S6K pathway. Thus, inhibition of the p70 S6 pathway may
      enhance chemotherapy-induced apoptosis in the treatment of IGF-II-overexpressing
      tumors.

PMID- 12192599
TI  - Exposure of human breast cancer cells to the anti-inflammatory agent indomethacin
      alters choline phospholipid metabolites and Nm23 expression.
AB  - We previously observed that changes in choline phospholipids of two malignant
      human mammary epithelial cells (HMECs) following treatment with a high dose of
      the cyclooxygenase (COX) inhibitor, indomethacin, mimicked changes following
      transfection with a metastasis suppressor gene, nm23. The similarity between
      response to indomethacin and nm23 transfection led us to 1) expand our (1)H NMR
      spectroscopy study of indomethacin treatment by determining the response at two
      doses for two nonmalignant and three malignant HMECs, 2) investigate COX-1 and
      COX-2 levels in HMECs and their relationship with choline phosholipid
      metabolites, and 3) determine changes in Nm23 expression following treatment with
      indomethacin. All HMECs exhibited a significant change in choline phospholipids
      following treatment with 300 microM indomethacin. At the lower dose of 50 microM,
      only nonmalignant HMECs and the estrogen-dependent malignant cell line, MCF-7,
      responded. COX-1 levels were significantly higher in malignant HMECs than in
      nonmalignant HMECs. A significant increase in Nm23 expression following 300
      microM indomethacin was detected in MCF-12A and MCF-7 cells but not in MDA-MB-231
      and MDA-MB-435 cells. These results suggest that COX-1 expression and its
      inhibition play a role in the choline phospholipid metabolism of HMECs, and the
      effect of indomethacin on HMECs may be mediated, in part, through upregulation of
      nm23.

PMID- 12192600
TI  - Mutational analysis of DBD*--a unique antileukemic gene sequence.
AB  - DBD* is a novel gene encoding an 89 amino acid peptide that is constitutively
      lethal to leukemic cells. DBD* was derived from the DNA binding domain of the
      human glucocorticoid receptor by a frameshift that replaces the final 21 C
      terminal amino acids of the domain. Previous studies suggested that DBD* no
      longer acted as the natural DNA binding domain. To confirm and extend these
      results, we mutated DBD* in 29 single amino acid positions, critical for the
      function in the native domain or of possible functional significance in the novel
      21 amino acid C-terminal sequence. Steroid-resistant leukemic ICR-27-4 cells were
      transiently transfected by electroporation with each of the 29 mutants. Cell kill
      was evaluated by trypan blue dye exclusion, a WST-1 tetrazolium-based assay for
      cell respiration, propidium iodide exclusion, and Hoechst 33258 staining of
      chromatin. Eleven of the 29 point mutants increased, whereas four decreased
      antileukemic activity. The remainder had no effect on activity. The
      nonconcordances between these effects and native DNA binding domain function
      strongly suggest that the lethality of DBD* is distinct from that of the
      glucocorticoid receptor. Transfections of fragments of DBD* showed that optimal
      activity localized to the sequence for its C-terminal 32 amino acids.

PMID- 12192601
TI  - Prostate cancer aggressiveness locus on chromosome 7q32-q33 identified by linkage
      and allelic imbalance studies.
AB  - The biologic aggressiveness of prostate tumors is an important indicator of
      prognosis. Chromosome 7q32-q33 was recently reported to show linkage to more
      aggressive prostate cancer, based on Gleason score, in a large sibling pair
      study. We report confirmation and narrowing of the linked region using finer
      scale genotyping. We also report a high frequency of allelic imbalance (AI)
      defined within this locus in a series of 48 primary prostate tumors from men
      unselected for family history or disease status. The highest frequency of AI was
      observed with adjacent markers D7S2531 (52%) and D7S1804 (36%). These two markers
      delineated a common region of AI, with 24 tumors exhibiting interstitial AI
      involving one or both markers. The 1.1-Mb candidate region contains relatively
      few transcripts. Additionally, we observed positive associations between
      interstitial AI at D7S1804 and early age at diagnosis (P=.03) as well as a high
      combined Gleason score and tumor stage (P=.06). Interstitial AI at D7S2531 was
      associated with a positive family history of prostate cancer (P=.05). These data
      imply that we have localized a prostate cancer tumor aggressiveness loci to
      chromosome 7q32-q33 that is involved in familial and nonfamilial forms of
      prostate cancer.

PMID- 12192602
TI  - N-myc modulates expression of p73 in neuroblastoma.
AB  - The human p73 gene is a homolog of p53, which has been localized to chromosome
      1p36 in a region that is frequently deleted in neuroblastoma. Transfection of the
      p73 gene into neuroblastoma cells that lack detectable p73 protein has been shown
      to result in growth suppression and to induce neuronal differentiation. In this
      study, we have identified by means of restriction landmark genome scanning (RLGS)
      a genomic fragment that was frequently reduced in intensity in neuroblastomas.
      The cloned fragment contained exon 1 of p73 as well as intronic and promoter
      sequences. We investigated the genomic and expression status of p73 and N-myc in
      34 neuroblastoma tumors and 12 neuroblastoma cell lines. Approximately a third of
      neuroblastomas in our series exhibited deletion of p73. Most tumors analyzed
      exhibited reduced expression of p73, as determined by quantitative RT-PCR, in the
      absence of detectable p73 gene deletion. The reduced expression of p73 correlated
      with overexpression of N-myc in a statistically significant manner. The N-myc
      gene was transfected into two neuroblastoma cell lines that lacked N-myc
      amplification to determine its effect on p73 RNA levels. p73 was detectable at
      low level by RT-PCR in untransfected SK-N-AS cells and became undetectable
      following N-myc transfection, whereas in SH-EP1 cells, p73 levels were
      substantially reduced following transfection but remained detectable. Our data
      suggest that the N-myc gene modulates expression of p73, allowing neuroblastoma
      cells to escape the growth suppressing properties of p73.

PMID- 12192607
TI  - Stylized transcript map of chromosome 4q35 encompassing the locus for a bipolar
      disorder susceptibility gene.

PMID- 12192603
TI  - Proteomic analysis of cytokeratin isoforms uncovers association with survival in
      lung adenocarcinoma.
AB  - Cytokeratins (CK) are intermediate filaments whose expression is often altered in
      epithelial cancer. Systematic identification of lung adenocarcinoma proteins
      using two-dimensional polyacrylamide gel electrophoresis and mass spectrometry
      has uncovered numerous CK isoforms. In this study, 93 lung adenocarcinomas (64
      stage I and 29 stage III) and 10 uninvolved lung samples were quantitatively
      examined for protein expression. Fourteen of 21 isoforms of CK 7, 8, 18, and 19
      occurred at significantly higher levels (P < .05) in tumors compared to
      uninvolved adjacent tissue. Specific isoforms of the four types of CK identified
      correlated with either clinical outcome or individual clinical-pathological
      parameters. All five of the CK7 isoforms associated with patient survival
      represented cleavage products. Two of five CK7 isoforms (nos. 2165 and 2091), one
      of eight CK8 isoforms (no. 439), and one of three CK19 isoforms (no. 1955) were
      associated with survival and significantly correlated to their mRNA levels,
      suggesting that transcription underlies overexpression of these CK isoforms. Our
      data indicate substantial heterogeneity among CK in lung adenocarcinomas
      resulting from posttranslational modifications, some of which correlated with
      patient survival and other clinical parameters. Therefore, specific isoforms of
      individual CK may have utility as diagnostic or predictive markers in lung
      adenocarcinomas.

PMID- 12192604
TI  - Antibody-directed effector cell therapy of tumors: analysis and optimization
      using a physiologically based pharmacokinetic model.
AB  - The failure of the cellular immune response to stop solid tumor growth has been
      the subject of much research. Although the mechanisms for tumor evasion of immune
      response are poorly understood, one viable explanation is that tumor-killing
      lymphocytes cannot reach the tumor cells in sufficient quantity to keep the tumor
      in check. Recently, the use of bifunctional antibodies (BFAs) has been proposed
      as a way to direct immune cells to the tumor: one arm of the antibody is specific
      for a known tumor-associated antigen and the other for a lymphocyte marker such
      as CD3. Injecting this BFA should presumably result in cross-linking of
      lymphocytes (either endogenous or adoptively transferred) with tumor cells,
      thereby enhancing therapy. Results from such an approach, however, are often
      disappointing--frequently there is no benefit gained by using the BFA. We have
      analyzed the retargeting of endogenous effector cells by BFA using a
      physiologically based whole-body pharmacokinetic model that accounts for
      interactions between all relevant species in the various organs and tumor. Our
      results suggest that the design of the BFA is critical and the binding constants
      of the antigen and lymphocyte binding epitopes need to be optimized for
      successful therapy.

PMID- 12192608
TI  - Association of a polymorphism in the promoter region of the serotonin 5-HT2C
      receptor gene with tardive dyskinesia in patients with schizophrenia.

PMID- 12192609
TI  - No occurrence of the glutamate transporter EAAT2 A206G polymorphism in
      schizophrenic subjects.

PMID- 12192610
TI  - Abnormal expression of epidermal growth factor and its receptor in the forebrain
      and serum of schizophrenic patients.
AB  - Epidermal growth factor (EGF) comprises a structurally related family of proteins
      containing heparin-binding EGF-like growth factor (HB-EGF) and transforming
      growth factor alpha (TGFalpha) that regulates the development of dopaminergic
      neurons as well as monoamine metabolism. We assessed the contribution of EGF to
      schizophrenia by measuring EGF family protein levels in postmortem brains and in
      fresh serum of schizophrenic patients and control subjects. EGF protein levels
      were decreased in the prefrontal cortex and striatum of schizophrenic patients,
      whereas the levels of HB-EGF and TGFalpha were not significantly different in any
      of the regions examined. Conversely, EGF receptor expression was elevated in the
      prefrontal cortex. Serum EGF levels were markedly reduced in schizophrenic
      patients, even in young, drug-free patients. Chronic treatment of animals with
      the antipsychotic drug haloperidol had no influence on EGF levels in the brain or
      serum. These findings suggest that there is abnormal EGF production in various
      central and peripheral tissues of patients with both acute and chronic
      schizophrenia. EGF might thus provide a molecular substrate for the pathologic
      manifestation of the illness, although additional studies are required to
      determine a potential link between impaired EGF signaling and the
      pathology/etiology of schizophrenia.

PMID- 12192611
TI  - Decreased phorbol ester binding in the parahippocampal gyrus from subjects with
      schizophrenia is not associated with changes in protein kinase C.
AB  - Combining in situ radioligand binding with autoradiography, we previously
      identified a reduction of [(3)H]phorbol 12,13-dibutyrate binding in the
      parahippocampal gyrus from schizophrenic subjects. To determine whether these
      changes were due to decreases in the level of protein kinase C, we measured
      [(3)H]phorbol 12,13-dibutyrate binding, levels of the protein kinase C isoforms
      alpha, beta, delta, epsilon, gamma, eta and theta, as well as protein kinase C
      activity in crude particulate membranes from parahippocampal gyri of 15
      schizophrenic and 15 control subjects. There was a significant decrease in the
      density (mean +/- SEM: 6.56 +/- 0.73 pmol mg(-1) vs 9.68 +/- 1.22 pmol mg(-1); P
      < 0.05) and affinity (mean K(D) +/- SEM: 4.64 +/- 0.34 nM vs 2.95 +/- 0.35 nM; P
      < 0.005) of [(3)H]phorbol 12,13-dibutyrate binding in homogenates from
      schizophrenic subjects. There were no significant changes in levels of the
      protein kinase C isoforms which are known to bind phorbol esters or in the
      activity of protein kinase C in membranes from schizophrenic subjects. These
      results suggest that there are changes in molecules capable of binding
      [(3)H]phorbol 12,13-dibutyrate, other than protein kinase C, in the
      parahippocampal gyrus from subjects with schizophrenia.

PMID- 12192612
TI  - Genome-wide multipoint linkage analyses of multiplex schizophrenia pedigrees from
      the oceanic nation of Palau.
AB  - The oceanic nation of Palau has been geographically and culturally isolated over
      most of its 2000 year history. As part of a study of the genetic basis of
      schizophrenia in Palau, we genotyped five large, multigenerational schizophrenia
      pedigrees using markers every 10 cM (CHLC/Weber screening set 6). The number of
      affected/unaffected individuals genotyped per family ranged from 11/21 to 5/5.
      Thus the pedigrees varied in their information for linkage, but each was capable
      of producing a substantial LOD score. We fitted a simple dominant and recessive
      model to these data using multipoint linkage analysis implemented by Simwalk2.
      Predictably, the most informative pedigrees produced the best linkage results.
      After genotyping additional markers in the region, one pedigree produced a LOD =
      3.4 (5q distal) under the dominant model. Seven of nine schizophrenics in the
      pedigree, mostly 3rd-4th degree relatives, share a 15-cM, 7-marker haplotype. For
      a different pedigree, another promising signal occurred on distal 3q, LOD = 2.6,
      for the recessive model. For two other pedigrees, the best LODs were modest,
      slightly better than 2.0 on 5q and 9p, while the fifth pedigree produced no
      noteworthy linkage signal. Similar to the results for other populations, our
      results suggest there are multiple genes conferring liability to schizophrenia
      even in the small population of Palau (roughly 21,000 individuals) in remote
      Oceania.

PMID- 12192613
TI  - Relationship between adverse effects of antipsychotic treatment and dopamine D(2)
      receptor polymorphisms in patients with schizophrenia.
AB  - Extrapyramidal adverse symptoms (EPS) represent a major type of adverse events in
      treatment with typical antipsychotic drugs which share high affinity to the
      dopamine D(2) receptor (DRD2). Genetic variants of this receptor may modulate the
      therapeutic response and the severity of adverse symptoms of antipsychotics. We
      analyzed nine known polymorphisms of the DRD2 in 665 schizophrenic patients with
      European Caucasian ethnic background and compared the intensity of acute
      dystonia, extrapyramidal symptoms, akathisia, and tardive dyskinesia between
      carriers of different DRD2 genotypes. In a subgroup of 40 patients with most
      severe extrapyramidal symptoms we sequenced the coding region including the exon
      intron junctions of the DRD2 gene. Functionally relevant DRD2 amino acid variants
      (Ser(310), Cys(311)) were rare or were not found at all (Ala(96)). Complete
      sequence analysis of sufferers from the most severe adverse effects revealed two
      new intronic polymorphisms and a silent polymorphism in exon 7, but no new amino
      acid variants beyond those which are already known. We found no significant
      association between these polymorphisms and the intensity of the different types
      of adverse neurologic effects of the antipsychotics. These results were obtained
      by correlating adverse events with each of the nine single nucleotide
      polymorphisms and by correlation with the estimated haplotypes. In conclusion,
      genetic variations in the DRD2 gene were no major predictors of the individually
      variable adverse effects from antipsychotic treatment in Caucasian schizophrenic
      patients.

PMID- 12192614
TI  - Higher scores of self reported schizotypy in healthy young males carrying the
      COMT high activity allele.
AB  - The gene for COMT is located on chromosome 22q11, an area that has been
      implicated in the pathogenesis of schizophrenia through linkage studies and
      through the detection of deletions in schizophrenics and velocardiofacial
      syndrome patients that often present psychotic symptomatology. Additionally
      catechol-O-methyl transferase activity has been found increased in schizophrenia
      and a functional polymorphism in the COMT gene itself has been associated with
      the disease, as well as with aggression in patients. We tested the hypothesis
      that COMT genotype for the functional Val158Met might contribute to the variance
      of self reported schizotypy and aggression scores in the normal population. We
      genotyped 379 healthy 18- to 24-year-old male individuals who had completed the
      PAS, SPQ and AQ questionnaires. Our results showed that self-reported schizotypy
      scores in both questionnaires were significantly related to COMT genotype (P =
      0.028 for the PAS and P = 0.015 for the SPQ) with individuals homozygous for the
      high activity allele showing the highest scores. No significant differences were
      detected for AQ scores. We conclude that the COMT genotype for the functional
      Val158Met polymorphism is correlated to self-reported schizotypy in healthy
      males. This finding is in the same direction as reported findings on
      schizophrenia and it adds to the list of evidence that COMT or a nearby gene in
      linkage disequilibrium is involved in the pathogenesis of the disease.

PMID- 12192615
TI  - A meta-analysis of the association between DRD4 polymorphism and novelty seeking.
AB  - A meta-analytical review of 20 studies (n = 3907) of the association between DRD4
      polymorphism and novelty seeking suggests the following conclusions: (a) on
      average, there is no association between DRD4 polymorphism and novelty seeking
      (average d = 0.06 with 95% CI of +/- 0.09), where 13 reports suggest that the
      presence of longer alleles is associated with higher novelty seeking scores and
      seven reports suggest the opposite; (b) there is a true heterogeneity among the
      studies (ie, unknown moderators do exist) but the strength of the association
      between DRD4 polymorphism and novelty seeking in the presence of any (unknown)
      moderator is likely to be weak; (c) search for moderators has not yielded any
      reliable explanation for the variability among studies. We propose that to find
      such moderators, theory-driven research for potential interaction, coupled with
      larger sample sizes should be employed. The growing availability of powerful
      statistical techniques, high-throughput genotyping and large numbers of
      polymorphic markers such as single nucleotide polymorphisms makes such proposed
      studies increasingly feasible.

PMID- 12192616
TI  - Serotonergic system and attention deficit hyperactivity disorder (ADHD): a
      potential susceptibility locus at the 5-HT(1B) receptor gene in 273 nuclear
      families from a multi-centre sample.
AB  - Attention deficit hyperactivity disorder (ADHD) is a highly heritable and
      heterogeneous disorder, which usually becomes apparent during the first few years
      of childhood. Imbalance in dopamine neurotransmission has been suggested as a
      factor predisposing to ADHD. However, evidence has suggested an interaction
      between dopamine and serotonin systems in the pathophysiology of the disorder.
      Studies using selective agonists of the different 5-HT receptors microinjected
      into selected brain structures have shown a positive modulating effect on the
      functional activities of the mesotelencephalic dopaminergic system. This suggests
      that some of the genetic predisposition to ADHD might be due to DNA variation at
      serotonin system genes. In this study, we investigated polymorphisms in HTR(1B)
      and HTR(2A) (which encode the serotonin receptors 5-HT(1B) and 5-HT(2A)
      respectively) in a European ADHD sample. Using haplotype based haplotype relative
      risk (HHRR) and transmission disequilibrium test (TDT) analyses, we observed
      significant preferential transmission of the allele 861G of the HTR(1B) in the
      total sample (for HHRR; chi(2) = 7.4, P = 0.0065 and TDT; (chi(2) = 6.4, P =
      0.014). Analysis of HTR(2A) failed to reveal evidence of association or linkage
      between the His452Tyr polymorphism and ADHD in the total sample. However, a
      significantly increased transmission of the allele 452His was observed in the
      Irish sample alone (chi(2) = 4.9, P = 0.026). These preliminary data suggest an
      important role for the serotonin system in the development of ADHD. Further
      studies, preferentially including different ethnic groups are required to
      substantiate these findings.

PMID- 12192617
TI  - Antiepileptic drugs and agents that inhibit voltage-gated sodium channels prevent
      NMDA antagonist neurotoxicity.
AB  - N-methyl-D-aspartate (NMDA) glutamate receptor antagonists are used in clinical
      anesthesia and are being developed as therapeutic agents for preventing
      neurodegeneration in stroke, epilepsy, and brain trauma. However, the ability of
      these agents to produce neurotoxicity in adult rats and psychosis in adult humans
      compromises their clinical usefulness. In addition, an NMDA receptor hypofunction
      (NRHypo) state might play a role in neurodegenerative and psychotic disorders,
      like Alzheimer's disease, bipolar disorder and schizophrenia. Thus, developing
      pharmacological means of preventing these NRHypo-induced effects could have
      significant clinically relevant benefits. NRHypo neurotoxicity appears to be
      mediated by a complex disinhibition mechanism that results in the excessive
      stimulation of certain vulnerable neurons. Here we report our findings that five
      agents (phenytoin, carbamazepine, valproic acid, lamotrigine, and riluzole),
      thought to possess anticonvulsant activity because they inhibit voltage-gated
      sodium channels, prevent NRHypo neurotoxicity. The ability of tetrodotoxin, a
      highly selective inhibitor of voltage-gated sodium channels, to prevent the same
      neurotoxicity suggests that inhibition of this ion channel is the likely
      mechanism of action of these five agents. We also found that three other
      anticonvulsants (felbamate, gabapentin and ethosuximide), whose mechanism is less
      clear, also prevent NRHypo neurotoxicity, suggesting that inhibition of voltage
      gated sodium channels is not the only mechanism via which anticonvulsants can act
      to prevent NRHypo neurotoxicity. Several of these agents have been found to be of
      clinical use in bipolar disorder. It would be of interest to determine whether
      these agents might have therapeutic benefits for conditions in which a NRHypo
      state may exist.

PMID- 12192618
TI  - A genome-wide scan shows significant linkage between bipolar disorder and
      chromosome 12q24.3 and suggestive linkage to chromosomes 1p22-21, 4p16, 6q14-22,
      10q26 and 16p13.3.
AB  - The present study reports a genomewide scan using linkage analysis for risk genes
      involved in bipolar disorder with 613 microsatellite markers including additional
      testing of promising regions. As previously published significant linkage was
      obtained at chromosome 12q24.3 with a two-point parametric lod score of 3.42 at
      D12S1639 including all members in both families (empirical P-value 0.00004,
      genome-wide P-value 0.0417). The multipoint parametric lod score at D12S1639 was
      3.63 (genome-wide P-value 0.0265). At chromosome 1p22-p21 a parametric, affecteds
      only two-point lod score of 2.75 at marker D1S216 was found (empirical P-value
      0.0002, genome-wide P-value 0.1622). A three-point lod score of 2.98 (genome-wide
      P-value 0.1022) at D1S216, and a multipoint non-parametric analysis with a
      maximum NPL-all score of 17.60 (P-value 0.00079) at D1S216 further supported this
      finding. A number of additional loci on chromosomes 4p16, 6q14-q22, 10q26 and
      16p13.3 yielded parametric lod scores around or above 2.

PMID- 12192619
TI  - Novel polymorphisms in the somatostatin receptor 5 (SSTR5) gene associated with
      bipolar affective disorder.
AB  - The somatostatin receptor 5 (SSTR5) gene is a candidate gene for bipolar
      affective disorder (BPAD) as well as for other neuropsychiatric disorders. The
      gene is positioned on chromosome 16p13.3, a region that has been implicated by a
      few linkage studies to potentially harbor a disease susceptibility gene for BPAD.
      Recent evidence shows that the dopamine D2 receptor (DRD2) and SSTR5 interact
      physically to form heterodimers with enhanced functional activity. Brain D2
      dopamine receptors are one of the major targets of neuroleptic treatments in
      psychiatric disorders. In this study we systematically screened the promoter and
      coding region of the SSTR5 gene for genetic variation that could contribute to
      the development of neuropsychiatric disorders. Eleven novel single nucleotide
      polymorphisms (SNPs) were identified including four missense SNPs, Leu48Met,
      Ala52Val, Pro109Ser and Pro335Leu. We carried out an association study of BPAD
      using 80 Danish cases and 144 control subjects, and replication analysis using 55
      British cases and 88 control subjects. For the Danish population, association was
      suggested between silent SNP G573A and BPAD (P = 0.008). For the British
      population we found association to BPAD with missense mutation Leu48Met (P =
      0.003) and missense mutation Pro335Leu (P = 0.004). The statistical significance
      of the association was, however, greatly reduced after correcting for multiple
      testing. When combining genotypes from Leu48Met and Pro335Leu into haplotypes,
      association to BPAD was found in the British population (P = 0.0007). This
      haplotype association was not replicated in the Danish population. Our results
      may indicate that the SSTR5 gene is involved in the etiology of BPAD or may exist
      in linkage disequilibrium with a susceptibility gene close to SSTR5. However,
      given the marginal statistical significance and the potential for false-positive
      results in association studies with candidate genes, further studies are needed
      to clarify this hypothesis.

PMID- 12192620
TI  - Neurotransmitter receptor-mediated activation of G-proteins in brains of suicide
      victims with mood disorders: selective supersensitivity of alpha(2A)
      adrenoceptors.
AB  - Abnormalities in the density of neuroreceptors that regulate norepinephrine and
      serotonin release have been repeatedly reported in brains of suicide victims with
      mood disorders. Recently, the modulation of the [(35)S]GTPgammaS binding to G
      proteins has been introduced as a suitable measure of receptor activity in
      postmortem human brain. The present study sought to evaluate the function of
      several G-protein coupled receptors in postmortem brain of suicide victims with
      mood disorders. Concentration-response curves of the [(35)S]GTPgammaS binding
      stimulation by selective agonists of alpha(2)-adrenoceptors, 5-HT(1A) serotonin,
      mu-opioid, GABA(B), and cholinergic muscarinic receptors were performed in
      frontal cortical membranes from 28 suicide victims with major depression or
      bipolar disorder and 28 subjects who were matched for gender, age and postmortem
      delay. The receptor-independent [(35)S]GTPgammaS binding stimulation by
      mastoparan and the G-protein density were also examined. The alpha(2A)
      adrenoceptor-mediated stimulation of [(35)S]GTPgammaS binding with the agonist
      UK14304 displayed a 4.6-fold greater sensitivity in suicide victims than in
      controls, without changes in the maximal stimulation. No significant differences
      were found in parameters of 5-HT(1A) serotonin receptor and other receptor
      mediated [(35)S]GTPgammaS binding stimulations. The receptor-independent
      activation of G-proteins was similar in both groups. Immunoreactive densities of
      G(alphai1/2)-, G(alphai3)-, G(alphao)-, and G(alphas)-proteins did not differ
      between suicide victims and controls. In conclusion, alpha(2A)-adrenoceptor
      sensitivity is increased in the frontal cortex of suicide victims with mood
      disorders. This receptor supersensitivity is not related to an increased amount
      or enhanced intrinsic activity of G-proteins. The new finding provides functional
      support to the involvement of alpha(2)-adrenoceptors in the pathogenesis of mood
      disorders.

PMID- 12192621
TI  - APOE-epsilon4 and APOE -491A polymorphisms in individuals with subjective memory
      loss.
AB  - The accurate clinical diagnosis of Alzheimer's disease can only be made with a
      high degree of certainty in specialized centres. The identification of predictive
      or diagnostic genetic factors may improve accuracy of disease prediction or
      diagnosis. One major genetic risk factor, the epsilon4 allele of the
      apolipoprotein E gene, is universally recognised. We have recently shown that the
      A allele of the apolipoprotein E, -491A/T promoter polymorphism is also an
      important risk factor for Alzheimer's disease in an Australian population. We
      designed the present study to investigate the association between apolipoprotein
      E genotype, -491A/T polymorphism, plasma apoE levels and the subjective
      experience of memory decline among 98 subjects and 49 age, gender and education
      matched normal controls. An increased frequency of the epsilon4 allele of
      apolipoprotein E was significantly associated with the 'memory complainers' group
      (OR = 2.35, P = 0.02) as was the A allele of the -491A/T polymorphism (OR = 2, P
      = 0.02). Among all subjects, only seven individuals were homozygous for both of
      these alleles, and six of these seven individuals belonged to the 'memory
      complainers' group. This sub-group also had relatively elevated plasma
      apolipoprotein E levels (P < 0.01) and tended to score lower on the Mini-Mental
      State Examination (MMSE) and Cambridge Cognition Test. These data suggest that
      the epsilon4 allele of apolipoprotein E and the -491A allele are over-represented
      among individuals who complain of memory difficulties. Follow-up studies should
      clarify whether these genotypes and phenotypes are useful in the prediction
      and/or diagnosis of Alzheimer's disease.

PMID- 12192622
TI  - Association between presenilin-1 Glu318Gly mutation and familial Alzheimer's
      disease in the Australian population.
AB  - Mutations in the presenilin-1 (PS-1) gene on chromosome 14 account for the
      majority of early-onset familial Alzheimer's disease (FAD) cases. To date, more
      than 90 mutations have been identified and, while most of these mutations are
      completely penetrant, the Glu318Gly mutation has been suggested to be partially
      penetrant. These findings indicate that it may play a similar role to
      apolipoprotein E (APOE)-epsilon4 by acting as a genetic risk factor for AD. In
      the current study, a total of 682 subjects were tested to assess the frequency of
      the Glu318Gly mutation in AD in the Australian population. The Glu318Gly mutation
      was identified in six sporadic late-onset AD patients, four FAD patients
      (unrelated) and in nine control subjects. The frequency of this mutation was
      highest in the familial AD group (8.7%) and lowest in control subjects (2.2%).
      When the mutation frequencies were compared, we found a statistically significant
      difference between the latter two groups (Fisher's exact test, P < 0.05). The
      genotype frequency of the Glu318Gly mutation in all AD cases and controls in the
      Australian population was 2.8%. This frequency is comparable to that observed for
      the Dutch population (3.2%), but not for the Finnish population (6.8% and 6.0%)
      or the Spanish population (5.3%). These findings show that the frequency of the
      Glu318Gly mutation is increased in FAD patients, suggesting a potential role as a
      genetic risk factor contributing to the pathogenesis of familial AD.

PMID- 12192623
TI  - A polymorphism of the brain-derived neurotrophic factor (BDNF) is associated with
      Alzheimer's disease in patients lacking the Apolipoprotein E epsilon4 allele.
AB  - Because of its implication in neuroprotection, formation of long lasting memories
      and a disturbed function in Alzheimer's disease (AD), brain-derived neurotrophic
      factor (BDNF) may represent an appropriate candidate gene conferring risk to AD.
      Recently, a single nucleotide polymorphism (C-270T) within the BDNF gene has been
      associated with late onset AD in a Japanese population giving an odds ratio (OR)
      of 3.8. Because of the importance of this finding we analysed the BDNF
      polymorphism in a German sample consisting of 210 patients with AD and 188
      cognitively healthy controls. The T-allele frequency was higher in patients with
      AD (11.9%) compared to controls (6.9%) (P = 0.035; OR = 2.26; 95% CI: 1.04-4.48).
      The risk conferred by the T-allele was stronger in patients who lack the ApoE
      epsilon4 allele giving an OR of 2.61 (1.21-5.64) P = 0.015, particularly in
      patients with early onset of the disease; OR 3.13 (1.32-7.43); P= 0.01. Due to
      the small number of patients showing both, lack of the ApoE epsilon4 allele and
      the BDNF T allele (n = 18), the result needs to be confirmed in a larger sample.
      The results suggest that the BDNF C-270T polymorphism is a relevant risk factor
      for AD particularly in patients lacking the ApoE epsilon4 allele in this German
      sample.

PMID- 12192624
TI  - DRD4 promoter SNPs and gender effects on Extraversion in African Americans.
AB  - There is strong evidence for genetic influences on personality traits. Interest
      in one such gene, the dopamine D4 receptor (DRD4) grew after an exon III
      polymorphism was associated with Novelty Seeking and related measures of
      Extraversion. However, the findings were not confirmed in later studies.
      Recently, a -521C/T single nucleotide polymorphism (SNP) within the promoter
      region of the DRD4 gene was found to be related to Novelty Seeking scores in
      populations from Japan and Hungary. Since little is known about the role DRD4
      plays in personality in other populations we evaluated if two DRD4 promoter SNPs,
      -521C/T and -616C/G, were related to personality traits in African Americans.
      Personality traits were measured by the NEO-FFI in 71 unrelated African
      Americans. Genotyping was performed using PCR-RFLP. Multivariate analyses of
      variance (MANOVA) were performed to evaluate the effects of gender and -616 and 
      521 genotypes on personality traits. A significant three-way interaction effect
      from gender, -616 genotype, and -521 genotype was observed for Extraversion
      scores (F(1,54) 5.86, P < 0.02). Subsequent analyses revealed that the
      association was mainly due to -521C/T genotype among females (P = 0.01). This
      study provides further evidence that genetic variation within the DRD4 promoter
      and gender differences contribute to variation in Novelty Seeking behaviors such
      as Extraversion.

PMID- 12192625
TI  - The short DRD4 repeats confer risk to attention deficit hyperactivity disorder in
      a family-based design and impair performance on a continuous performance test
      (TOVA).
AB  - One particular candidate gene, the dopamine D4 receptor (DRD4), has been the
      focus of intense study regarding ADHD since the original investigation by La
      Hoste et al, an observation confirmed by a recent metaanalysis. However, two
      previous studies from Israel failed to observe this association. We have now
      recruited an additional sample and, overall, in the combined sample of 178 triads
      we observe using the transmission disequilibrium test, preferential transmission
      of the short allele. Additionally, we now report the effect of the DRD4 repeat
      region on the Test Of Variables of Attention (TOVA), a widely used computerized
      continuous performance test. Probands with the short exon III repeat performed
      significantly worse on the TOVA measured both by errors of commission and
      response time variable. Intriguingly, a 'dose effect' was observed. Increasing
      repeat size is accompanied by a reduced number of errors of commission and a
      significant difference is observed between the 2 vs 7 repeats. On the whole, our
      results lend credence to the notion that the relationship between the DRD4
      receptor and ADHD is complex and may be reflecting linkage disequilibrium between
      the 7 or long DRD4 exon III repeats and a 'true' risk allele in this gene or a
      neighboring locus.

PMID- 12192626
TI  - Serotonin transporter gene promoter variants do not explain the
      hyperserotoninemia in autistic children.
AB  - Autism is a biologically-heterogeneous disease. Distinct subgroups of autistic
      patients may be marked by intermediate phenotypes, such as elevated serotonin (5
      HT) blood levels, potentially associated with different underlying disease
      mechanisms. This could lead to inconsistent genetic association results, such as
      those of prior studies on serotonin transporter (5-HTT) gene promoter variants
      and autistic disorder. Contributions of 5-HTT gene promoter alleles to 5-HT blood
      levels were thus investigated in 134 autistic patients and 291 first-degree
      relatives. Mean 5-HT blood levels are 11% higher in autistic patients carrying
      the L/L genotype, compared to patients with the S/S or S/L genotype; this trend
      is not observed in first-degree relatives. The probability of inheriting L or S
      alleles is significantly enhanced in patients with 5-HT blood levels above or
      below the mean, respectively (P < 0.05), but quantitative TDT analyses yield a
      non-significant trend (P = 0.10), as this polymorphism explains only 2.5% of the
      variance in 5-HT blood levels of autistic patients. In conclusion, 5-HTT gene
      promoter variants seemingly exert a small effect on 5-HT blood levels in autistic
      children, which largely does not account for hyperserotoninemia. Nonetheless, the
      inconsistent outcome of prior association studies could partly stem from a
      selection bias of hyper- or hypo-serotoninemic probands.

PMID- 12192627
TI  - Absence of association between a polymorphic GGC repeat in the 5' untranslated
      region of the reelin gene and autism.
AB  - Autism is a complex neurodevelopmental disorder with severe cognitive and
      communication disabilities, that has a strong genetic predisposition. Reelin, a
      protein involved in neuronal migration during development, is encoded by a gene
      located on 7q22, within the candidate region on 7q showing increased allele
      sharing in previous genome scans. A case/control and family-based association
      study recently reported a positive association between a trinucleotide repeat
      polymorphism (GGC) located in the 5' untranslated region (UTR) of the reelin gene
      and autism. We performed a transmission disequilibrium test (TDT) analysis of the
      5'UTR polymorphism in 167 families including 218 affected subjects (117 trios and
      50 affected sib pairs) and found no evidence of linkage/association. Our results
      do not support previous findings and suggest that this GGC polymorphism of the
      reelin gene is unlikely to be a major susceptibility factor in autism and/or
      genetic heterogeneity.

PMID- 12192628
TI  - 5HT1Dbeta Receptor gene implicated in the pathogenesis of Obsessive-Compulsive
      Disorder: further evidence from a family-based association study.
AB  - Obsessive-Compulsive Disorder (OCD) is a psychiatric condition with strong
      evidence for a genetic component and for the involvement of genes of the
      serotonin system. In a recent family-based association study we reported an
      association between the G allele of the G861C polymorphism of the 5HT1Dbeta
      receptor gene and OCD. The aim of the present study was to further investigate
      for the presence of linkage disequilibrium between each of two polymorphisms of
      the 5HT1Dbeta receptor gene and OCD in a larger sample of OCD families. In a
      total of 121 families the G861C and the T371G polymorphisms of the 5HT1Dbeta
      receptor gene were genotyped using standard protocols. The genotyping data were
      analyzed with a new extension of the Transmission Disequilibrium Test (FBAT). The
      phenotypes considered in the analyses were the diagnosis of OCD and two
      quantitative phenotypes related to the diagnosis and clinically relevant, ie, the
      age at onset and the severity of OCD symptoms. We confirmed the previously found
      preferential transmission of the G861 allele to the affected subjects (z = 2.262,
      P = 0.02). No significant association was found between the polymorphism and the
      quantitative phenotypes considered. These results represent a confirmation of our
      previous published study and thus, could have important implications for the role
      of the 5HT1Dbeta receptor gene in the pathogenesis and treatment of OCD. Further
      genetic investigations on this marker considering additional polymorphisms and
      other quantitative phenotypes related to OCD are warranted.

PMID- 12192629
TI  - Depression: reduced number of granule cells in the hippocampus of female, but not
      male, rats due to prenatal restraint stress.
AB  - It has been hypothesized that decreased neurogenesis in the dentate gyrus may be
      involved in mediating depressive disorders, which are 1.5-3 times more frequent
      in women than in men. Additionally, prenatal stress may increase the risk of
      developing depression in adulthood. However, the interrelations between prenatal
      stress and the development of depression in adulthood, preferentially in females,
      are not understood. Here, we subjected pregnant rats to a single 20-min period of
      restraint stress on day 18 after mating. When the offspring were 75 days of age,
      the numbers of granule cells and pyramidal cells (area CA1-3) in the hippocampus
      were analyzed with the optical fractionator. The Cavalieri's principle was
      applied to analyze the volumes of both granule cell layer and pyramidal cell
      layer in the hippocampus. Prenatally stressed females, but not males, had reduced
      numbers of hippocampal granule cells compared to their non-prenatally stressed
      counterparts. This is the first report of a sex-specific difference concerning
      the reduction of the number of hippocampal granule cells due to prenatal stress.
      In humans, prenatal stress may induce cell loss in the granule cells of the
      hippocampus preferentially in females compared to males, and this may be a sex
      specific predisposing factor for the development of depression in adulthood.

PMID- 12192631
TI  - [Missing medical care?].

PMID- 12192632
TI  - [Smoking cessation for hospital staff. A controlled intervention study].
AB  - BACKGROUND AND OBJECTIVE: Smoking prevalence in Germany remains high instead of
      public information and education. Smoke free hospitals are propagated, but
      frequently the smoking prevalence in hospital staff is even higher than in the
      general population. The objectives of the study were to determine the prevalence
      of smoking amongst hospital employees in a German teaching hospital and
      subsequently to promote and optimise smoking cessation within controlled trial
      with additional evaluation of mindfulness based stress reduction, supported by a
      common workplace action. PATIENTS AND METHODS: A hospital survey was carried out
      by anonymous questionnaires. Participation in a physician-supervised smoking
      cessation program with nicotine replacement, brief intervention and,
      additionally, in a 20-hour stress reduction program over 8 weeks (group B) was
      offered to all smokers. Primary outcomes were abstinence rates at 3 months,
      secondary endpoints included abstinence rates at 6 months, cigarette consumption
      in smokers and expiratory CO-concentration. RESULTS: Out of 345 employees 296 (86
      %) revealed their smoking status, 140 were smokers (47,3 %). 116 of 140 smokers
      agreed with participation in a smoking cessation program. 53 subjects
      participated additionally in the stress reduction groups (Group B), 63 subjects
      wished no additional stress reduction (Group A). Abstinence rates at 3 and 6
      months were 38,2 % and 29,7 % for all subjects. Participants with stress
      reduction showed non-significant higher abstinence rates (3 months: A: 35 % vs.
      B: 42 % and 6 months: A: 20 % vs. B: 41,2 %), a significant lower CO
      concentration and a lower smoking intensity in recurrent smokers. CONCLUSION:
      With a common work place action a substantial part of employees quits smoking.
      Thus, the study provides support for the active promotion of physician-supervised
      smoking cessation programs among hospital employees. Supportive mindfulness-based
      stress reduction may enhance smoking cessation, yet has to be further tested in
      larger randomised controlled trials.

PMID- 12192633
TI  - [Infections and diseases after travelling].
AB  - BACKGROUND AND OBJECTIVE: With intensifying international travel numbers of
      travel associated infections and diseases will increase. Systematic studies on
      infections and diseases with regard to the travel destination in tropical and
      subtropical areas are scarce in Germany. PATIENTS AND METHODS: Data regarding
      travel destination, reason, type and duration of travel, symptoms, clinical
      findings, laboratory results as well as diagnoses of 2024 patients (male 1010,
      mean age 35 years; female 1014, mean age 33 years) presenting at the outpatient
      clinic of the Institute of Tropical Medicine Berlin after returning from travel
      to tropical or subtropical areas were assessed. RESULTS: The most frequent
      reasons for consultation were diarrhea (33 %), fever (17 %) and skin affections
      (14 %). A definitive diagnosis was established in 31 % (635). Significant
      differences were found for prevalences of infectious diseases with regard to
      travel destinations. 1.5 % of the travellers had contracted malaria. Only 34% of
      the returnees from malaria-endemic areas had taken chemoprophylaxis; in case of
      travel to Africa and Asia, chemoprophyplaxis corresponded to international
      standards in only 48 % and 23%, respectively. Giardia lamblia was the most
      frequently detected intestinal pathogen. Blastocystis hominis was found to be
      significantly associated with diarrhea. CONCLUSIONS: Most of the travel
      associated infections are self-limited. In case of fever, malaria and potentially
      hemorrhagic fever should be excluded and be followed by a stepwise investigation
      on the cause of fever. In case of diarrhea, parasitologic investigations should
      be performed by an experienced laboratory and fresh stool samples should be used.
      Intensive co-operation will be necessary between physician, pharmacists and
      others active in the field of travel medicine in order to address the
      shortcomings in chemoprophylaxis for malaria. An increasing need for expertise in
      tropical and travel medicine, especially among private physicians is expected.

PMID- 12192634
TI  - [An older female patient with refractory anemia and hemochromatosis].
AB  - CASE HISTORY AND CLINICAL FINDINGS: A 69-year-old woman was admitted because of a
      normocytic anemia. One year before an acute B19 parvovirus infection had been
      diagnosed, but the anemia was attributed to intestinal bleeding caused by a
      dysplastic colonic polyp. However, anemia persisted despite polypectomy. There
      was an excessive elevation of serum ferritin. ADDITIONAL EXAMINATIONS: A bone
      marrow biopsy and aspirate led to the diagnosis of a myelodysplastic syndrome
      (pure sideroblastic anemia). Ultrasound demonstrated advanced fibrosis of the
      liver. Fibrosis in association with severe parenchymatous siderosis was also
      demonstrated by histology. Analysis of the hemochromatosis gene (B-HFE, nt 845,
      G/A) was negative. DIAGNOSIS, THERAPY AND CLINICAL COURSE: The patient had
      secondary hemochromatosis due to a myelodysplastic syndrome. An acute infection
      with parvovirus B19 had been noted at the time of the first admission, one year
      before MDS was diagnosed. At that time, hemochromatosis had already caused
      fibrosis of the liver. However, complete regression of organ siderosis was
      achieved by deferoxamine administration. The myelodysplastic syndrome itself did
      not show any progression even 7 years after the diagnosis was established.
      CONCLUSION: Our case demonstrates the uncommon association between sideroblastic
      anemia and secondary hemochromatosis. Acute parvovirus infection may induce
      severe anemia in myelodysplastic syndromes. In acute B19 parvovirus infections an
      underlying hematologic disease should be excluded.

PMID- 12192635
TI  - [Diagnosis and treatment of acne inversa].

PMID- 12192636
TI  - [How would chronic heart insufficiency actually be treated today?].

PMID- 12192637
TI  - [Ethical implications of evidence-based medicine].

PMID- 12192638
TI  - [How would a hypogammaglobulinemia be messed up diagnostically and
      therapeutically?].

PMID- 12192640
TI  - Mutations of the selenoprotein N gene, which is implicated in rigid spine
      muscular dystrophy, cause the classical phenotype of multiminicore disease:
      reassessing the nosology of early-onset myopathies.
AB  - Multiminicore disease (MmD) is an autosomal recessive congenital myopathy
      characterized by the presence of multiple, short core lesions (known as
      "minicores") in most muscle fibers. MmD is a clinically heterogeneous condition,
      in which four subgroups have been distinguished. Homozygous RYR1 mutations have
      been recently identified in the moderate form of MmD with hand involvement. The
      genes responsible for the three other forms (including the most prevalent
      phenotype, termed the "classical" phenotype) remained, so far, unknown. To
      further characterize the genetic basis of MmD, we analyzed a series of 62
      patients through a combined positional/candidate-gene approach. On the basis of
      clinical and morphological data, we suspected a relationship between classical
      MmD and the selenoprotein N gene (SEPN1), which is located on chromosome 1p36
      (RSMD1 locus) and is responsible for the congenital muscular dystrophy with rigid
      spine syndrome (RSMD). A genomewide screening, followed by the analysis of 1p36
      microsatellite markers in 27 informative families with MmD, demonstrated linkage
      to RSMD1 in eight families. All showed an axial myopathy with scoliosis and
      respiratory failure, consistent with the most severe end of the classical MmD
      spectrum; spinal rigidity was evident in some, but not all, patients. We excluded
      linkage to RSMD1 in 19 families with MmD, including 9 with classical MmD.
      Screening of SEPN1 in the 8 families that showed linkage and in 14 patients with
      classical sporadic disease disclosed 9 mutations affecting 17 patients (12
      families); 6 were novel mutations, and 3 had been described in patients with
      RSMD. Analysis of three deltoid biopsy specimens from patients with typical RSMD
      revealed a wide myopathological variability, ranging from a dystrophic to a
      congenital myopathy pattern. A variable proportion of minicores was found in all
      the samples. The present study represents the first identification of a gene
      responsible for classical MmD, demonstrates its genetic heterogeneity, and
      reassesses the nosological boundaries between MmD and RSMD.

PMID- 12192643
TI  - [Proceedings of the 8th International Symposium of the Reina Sofia Institute of
      Nephrology Research. Barcelona, Spain. November 15-16, 2001].

PMID- 12192644
TI  - Adoption of animal welfare principles by UK regulators.

PMID- 12192641
TI  - Association between a high-expressing interferon-gamma allele and a lower
      frequency of kidney angiomyolipomas in TSC2 patients.
AB  - Tuberous sclerosis complex (TSC) is a familial hamartoma syndrome in which renal
      involvement is common and, at times, life threatening. We have investigated the
      potential effect of a non-TSC gene on renal disease in a cohort of 172 TSC
      patients with TSC2 mutations. Patients were genotyped for an interferon-gamma
      (IFN-gamma) microsatellite polymorphism, within intron 1, for which one common
      allele (allele 2, with 12 CA repeats) has been shown to have a higher expression
      of IFN-gamma. A chi(2) analysis was used to examine the association between IFN
      gamma allele 2 and the development of kidney angiomyolipomas (KAMLs) in this TSC2
      cohort. Because of the age-dependent development of KAMLs in TSC, we initially
      focused on the 127 patients who were >5 years old. Additional subgroup analyses
      were done to investigate the influence of age and gender. The
      transmission/disequilibrium test (TDT) was also performed in a subset of this
      cohort (46 probands) for whom parent and/or sibling samples were available for
      analysis. Both chi(2) analysis and TDT suggested an association between IFN-gamma
      allele 2 and the absence of KAMLs in patients who have known TSC2 mutations.
      Among the 127 patients who were >5 years old, KAMLs were present in 95 (75%) and
      were absent in 32 (25%). In the group with KAML present, the frequency of IFN
      gamma allele 2 was 56%; in the group with KAML absent, the frequency of IFN-gamma
      allele 2 was significantly higher, at 78% (P=.02, by chi(2) analysis). The family
      based TDT analysis gave similar results, with a TDT statistic (TDT chi2=5.45)
      corresponding to a P value of.02. Subgroup analyses show that both age and gender
      may influence the impact of this association. Although these results should be
      replicated in other populations with TSC, the present study suggests that
      modifier genes play a role in the variable expression of TSC and also suggests a
      potential therapy for KAMLs in patients with TSC.

PMID- 12192645
TI  - Festschrift Urology Conference in Honor of Dr. Thomas A. Stamey. September 29-30,
      2000. Stanford, California, USA.

PMID- 12192642
TI  - A genomewide screen for autism-spectrum disorders: evidence for a major
      susceptibility locus on chromosome 3q25-27.
AB  - To identify genetic loci for autism-spectrum disorders, we have performed a two
      stage genomewide scan in 38 Finnish families. The detailed clinical examination
      of all family members revealed infantile autism, but also Asperger syndrome (AS)
      and developmental dysphasia, in the same set of families. The most significant
      evidence for linkage was found on chromosome 3q25-27, with a maximum two-point
      LOD score of 4.31 (Z(max )(dom)) for D3S3037, using infantile autism and AS as an
      affection status. Six markers flanking over a 5-cM region on 3q gave Z(max dom)
      >3, and a maximum parametric multipoint LOD score (MLS) of 4.81 was obtained in
      the vicinity of D3S3715 and D3S3037. Association, linkage disequilibrium, and
      haplotype analyses provided some evidence for shared ancestor alleles on this
      chromosomal region among affected individuals, especially in the regional
      subisolate. Additional potential susceptibility loci with two-point LOD scores >2
      were observed on chromosomes 1q21-22 and 7q. The region on 1q21-22 overlaps with
      the previously reported candidate region for infantile autism and schizophrenia,
      whereas the region on chromosome 7q provided evidence for linkage 58 cM distally
      from the previously described autism susceptibility locus (AUTS1).

PMID- 12192646
TI  - Giant cell tumor of the breast.

PMID- 12192648
TI  - E-novation. Fast forward.

PMID- 12192649
TI  - E-novation. 'e' type.

PMID- 12192647
TI  - Intrahepatic cholangiocarcinoma arising in autosomal dominant polycystic kidney
      disease.

PMID- 12192650
TI  - E-novation. Band on the run.

PMID- 12192652
TI  - E-novation. Web feat.

PMID- 12192651
TI  - E-novation. Service with a smile.

PMID- 12192653
TI  - E-novation. That was then, this is now.

PMID- 12192654
TI  - On Stephen Jay Gould.

PMID- 12192655
TI  - Political, not scientific, birth control solutions.

PMID- 12192656
TI  - A birth control alternative.

PMID- 12192658
TI  - A soldier's view of the USAMRIID.

PMID- 12192657
TI  - Ribonucleases in ruminants.

PMID- 12192659
TI  - Assessment of P3a and P3b after moderate to severe brain injury.
AB  - The purpose of the study was to examine the P3a and P3b components of the event
      related brain potential (ERP) in patients sustaining moderate to severe brain
      injury. Electrophysiological and behavioral responses were recorded in brain
      injured (N = 18) and healthy control (N = 21) participants performance of an
      auditory 3-stimulus distractor paradigm. Auditory stimuli consisted of a series
      of repetitive standard tones (75 ms), occasionally interrupted by equiprobable
      target (25 ms) and distractor sounds (white noise). Tone duration discrimination
      accuracy was similar in patients and controls, but patients had prolonged
      reaction times to targets. The reaction time delay was paralleled by a
      prolongation of P3b latency to targets in the patient group relative to controls.
      The stimulus and task dependent modulation of ERP responses in the brain injury
      group was similar to that of controls in terms of the spatial distribution of
      ERPs over the scalp. However, the brain injury group had attenuated P3a and P3b
      amplitudes to distractor and target stimuli, respectively. The
      electrophysiological data suggest a deficit in the allocation of attentional
      resources to the processing of deviant stimuli in the brain injury group.

PMID- 12192660
TI  - Reduced sensitivity of the N400 and late positive component to semantic congruity
      and word repetition in left temporal lobe epilepsy.
AB  - We studied 14 patients with well-characterized refractory temporal lobe epilepsy
      (TLE), 7 with right temporal lobe epilepsy (RTE) and 7 with left temporal lobe
      epilepsy (LTE), on a word repetition ERP experiment. Much prior literature
      supports the view that patients with left TLE are more likely to develop verbal
      memory deficits, often attributable to left hippocampal sclerosis. Our main
      objectives were to test if abnormalities of the N400 or Late Positive Component
      (LPC, P600) were associated with a left temporal seizure focus, or left temporal
      lobe dysfunction. A minimum of 19 channels of EEG/EOG data were collected while
      subjects performed a semantic categorization task. Auditory category statements
      were followed by a visual target word, which were 50% "congruous" (category
      exemplars) and 50% "incongruous" (non-category exemplars) with the preceding
      semantic context. These auditory-visual pairings were repeated pseudo-randomly at
      time intervals ranging from approximately 10-140 seconds later. The ERP data were
      submitted to repeated-measures ANOVAs, which showed the RTE group had generally
      normal effects of word repetition on the LPC and the N400. Also, the N400
      component was larger to incongruous than congruous new words, as is normally the
      case. In contrast, the LTE group did not have statistically significant effects
      of either word repetition or congruity on their ERPs (N400 or LPC), suggesting
      that this ERP semantic categorization paradigm is sensitive to left temporal lobe
      dysfunction. Further studies are ongoing to determine if these ERP abnormalities
      predict hippocampal sclerosis on histopathology, or outcome after anterior
      temporal lobectomy.

PMID- 12192661
TI  - Cognitive ERPs in depressive and anxiety disorders during tonal and phonetic
      oddball tasks.
AB  - This report compares event-related brain potentials (ERPs) of patients having a
      depressive disorder alone (n = 58), an anxiety disorder alone (n = 22),
      comorbidity of these disorders (n = 18), and healthy controls (n = 49). ERPs were
      recorded from 30 electrode sites during auditory oddball tasks using consonant
      vowel syllables (phonetic) or complex tones (tonal). Overlapping ERP components
      were identified and measured using covariance-based principal components
      analysis. An early P3 subcomponent (P315) was larger in patients having an
      anxiety disorder alone when compared to depressed patients with or without an
      anxiety disorder and healthy controls, whereas a late P3 subcomponent (P400) was
      larger in patients having comorbidity of anxiety and depressive disorders than in
      the other groups. Also, the N2-P3 complex showed task-dependent hemispheric
      asymmetries, including larger N2-P3 amplitude over left than right
      temporoparietal sites during the phonetic oddball task. This hemispheric
      asymmetry was greatest in patients having a depressive disorder alone and
      smallest in patients having an anxiety disorder alone. The opposite nature of the
      alterations of hemispheric asymmetry and early P3 amplitude in depressive and
      anxiety disorders underscores the importance of taking comorbidity with anxiety
      into account in studies of cognitive ERPs in depressive disorders.

PMID- 12192662
TI  - The long and the short of it: influence of interstimulus interval on auditory
      P300 abnormalities in schizophrenia.
AB  - Event-related brain potentials were recorded from 10 patients with DSM-IV
      schizophrenia (9 men) and 10 healthy control subjects (9 men) during the
      performance of two auditory oddball tasks, one using a 1.5 second interstimulus
      interval (ISI), the other using an 8 second ISI. P300 amplitude to target tones
      (.20 probability) and standard tones (.80 probability) were measured from midline
      electrodes Fz, Cz, and Pz. Results showed different effects of ISI in the two
      groups. Controls showed a slight decrease in P300 amplitude to targets but a
      marked increase in P300 to standards with the increase in ISI. In contrast,
      schizophrenic patients showed no change in the P300 to targets and a relatively
      small increase in P300 to standards with the ISI increase. Moreover, relative to
      the controls, P300 amplitude to targets was reduced in the schizophrenic patients
      at the short but not the long ISI. Implications for the cognitive significance of
      the P300 and its reduction in schizophrenia are discussed.

PMID- 12192663
TI  - P3a and P3b auditory ERPs in HIV patients receiving anti-viral medication.
AB  - The effects of human immunodeficiency virus (HIV) infection on central nervous
      system function were studied with the P3a and P3b event-related brain potentials
      (ERPs) in patients with HIV compared to unaffected matched controls (n =
      14/group). All patients were on anti-viral medication for at least 2 months
      before testing. Auditory stimuli were employed in an easy 2-stimulus oddball
      discrimination task to obtain a typical P3b (P300) subcomponent. A 3-stimulus
      distractor paradigm also was employed in which the target/standard discrimination
      was very difficult, and an infrequent high-pitched tone non-target was presented
      to elicit the P3a subcomponent. Subjects responded only to the target stimulus in
      each task. P3a amplitude was significantly smaller for HIV compared to control
      subjects. No reliable P3b effects were obtained. The findings suggest that P3a
      rather than P3b may be a more sensitive measure of cognitive impairment in HIV
      patients on anti-viral medication.

PMID- 12192666
TI  - G-induced loss of consciousness (GLOC): an aviation psychology challenge.

PMID- 12192667
TI  - [The search for a precise method of measurement in psychical experiments].
AB  - In a series of three brief case studies, it is reconstructed how cognition and
      psychic activity were explored as energetic and economic transformations in a
      variety of experimental settings. 1. In the 1870s, the German psychiatrist Emil
      Kraepelin started his search for an objective measurement of cognitive
      performance in which he engaged over several decades. His investigations resulted
      in a graphic representation of cognitive efficiency, the "arbeitscurve",
      delineating the numbers of additions per time interval in close resemblance to
      representations of machine efficiency. 2. At the turn of the century, the
      American nutrition scientist and agronomist Wilbur Olin Atwater convinced himself
      in a series of precision measurements that the human motor was a so perfectly
      closed input-output system that he rejected any mental surplus in the form of
      cognitive energy transformations as contradictions to the principle of the
      conservation of energy. 3. At the beginning of the twentieth century and on the
      basis of Atwater's results, the German psychiatrist Hans Berger stipulated a
      special form of psychic energy for mediating between the principle of the
      conservation of energy and mental causality. Berger attempted to quantify psychic
      energy as one factor of brain metabolism. In the three cases of precision
      investigations into psychic life presented here, the experimental space of
      psychophysiology turned mental activity into a form of machine-like behavior.

PMID- 12192668
TI  - [Scientific methods in 19th century clinical laboratories].
AB  - In the middle of the 19th century the first chemical laboratories were
      established at hospitals and clinics in Central Europe which performed chemical
      analyses for purposes of practical medicine and clinical research. A
      characteristic feature of these new laboratories was the use of measuring
      instruments. The results of these chemical methods could serve as "signs" in the
      diagnosis of diseases. A great step forward was the introduction of
      "quantitative" data as results of measurements. They allowed a greater
      differentiation in the description of phenomena compared with the "qualitative"
      data used before. Another important feature of the new signs is the possibility
      to derive from it knowledge of causal relations of physiological and pathological
      processes in the organism. The influence of this methodological change on the
      thinking of the physicians at the sickbed is discussed using several examples.
      The "chemical signs" were used in the description of diseases and for the
      "quantification of health" by use of "normal values" which allow a discrimination
      between health and disease. Chemical quantities became also important for the
      description and examination of functional systems in the body, e.g. the
      metabolism.

PMID- 12192669
TI  - Reaction of monosaccharides with proteins: possible evolutionary significance.
AB  - Measurements were made of the rate of condensation of various monosaccharides
      with amino groups of hemoglobin to form Schiff base linkages. The reactivity of
      each sugar was dependent on the extent to which it exists in the open (carbonyl)
      structure rather than in the ring (hemiacetal or hemiketal) structure. Among the
      15 monosaccharides tested, aldoses showed higher reactivities than ketoses.
      Glucose was the least reactive of the aldohexoses. The emergence of glucose as
      the primary metabolic fuel may be due in part to the high stability of its ring
      structure which limits potentially deleterious nonenzymatic glycosylation of
      proteins.

PMID- 12192670
TI  - Atomism, atheism, and the spontaneous generation of human beings: the debate over
      the natural origin of the first humans in seventeenth-century Britain.

PMID- 12192671
TI  - Darwinism and death: devaluing human life in Germany 1859-1920.

PMID- 12192672
TI  - [A bibliographic study on Tongui-bigan with a special reference to its influence
      on Japan and China].
AB  - In this work my main focus was put on two things; first, to examine the history
      of publication of Tongui - bogam within the nation with particular interest in
      the changing aspect observed from the bibliographical terms, and second, to
      examine the process through which Tongui - bogam was introduced to Japan and
      China, and the influence the book brought the two nations. Some of the findings
      concerning the domestic publication of Tongui - bogam are as follows. The first
      printing of the book was made in 1613, under the auspice of Naeui - won, one of
      the government organs in the capital in charge of medical affairs. It was printed
      with wooden movable type carved at Hullyeon - togam, the military training
      bureau. As for the question of the history of the domestic publication of Tongui 
      bogam after the first printing in 1613, we don't have enough data yet. Although
      there are many different editions of Tongui - bogam extant today, with different
      size and different font each, I could find so far only three copies which carry
      the data concerning its publication, one printed in 1659 by the Kyongsang
      provincial government with newly engraved woodblock, one printed in 1754 again by
      the Kyongsang provincial government with re-engraved woodblock, and one printed
      in 1814 by the Cholla provincial government with newly re-engraved woodblock.
      Each of the three was a revised edition at the time of its publication because
      every time it was based on the copy corrected by Naeui - won. In addition to the
      above mentioned three different editions of Tongui - bogam, three are quite a few
      copies originally printed with wooden movable type of different font, at various
      time and various places. None of them has any record concerning the date and
      place of its publication, and none of them shows that it was based on the Naeui
      won corrected version as a mother copy. Accordingly, all of them carry quite a
      few erratum misprinting and it seems quite certain that all of them were produced
      before 1659. I also feel that the 1724 Japanese edition was based on one of the
      pre - 1659 copies. In Japan, the first publication of Tongui - bogam was made in
      the year of 1724 (the 9th year of Kyoho in Japanese year title) under the auspice
      of the Japanese government i.e. the Tokugawa Bakuf. The book carries a preface
      written by a man named Fubihara, then the vice president of national university,
      and a postscript written by Minamoto mototoru, a government attached monk
      physician. It was a woodblock printing and the title of the book was "Kankoku -
      Teisei Tongui - bogam. The reason the word "Kankoku-Teisei" the Revised Edition
      Printed with Officially Engraved Woodblocks", was added to the title was that the
      publication was made by the government and before publication the government
      ordered Minamoto to read through the original Tongui-bogam throughly and make
      corrections if any misprintings be found. Minamoto also put the so-called kunto
      marks, the Japanese way of punctuation system on the original text all the way so
      that they could read it in the their own way. As the question of what edition of
      Tongi - bogam the Japanese used as a mother copy and whwn and how the mother copy
      had been brought to Japan are not clear at all. But judging from the fact that it
      carries quite a few erratum in spite of their efforts at proofreading before
      engraving the woodblock, it seems likely that Tongui - bogam they used as a
      mother copy was the one which was printed in Korea before 1659. In 1659 Tongui
      bogam was published in Korea by the Kyongsang provincial government in Taegu with
      newly engraved woodblock. According to the attached record concerning its
      publication, it was a revised edition based on the Naeui - won corrected-copy,
      and this edition carries no misprintings in it at all. On the other hand, among
      the various editions of the extant Tongui - bogam today we can find some copy
      which, originally printed from wooden movable type, carries almost the same
      misprinting as those found in the 1724 Japanese edition. In other words, we are
      quite certain that the mother copy of the 1724 Japanese edition was brought to
      Japan before the Naeui - won - corrected - edition began to appear in Korea in
      1659. The second publication of Tongui - bogam in Japan was made in 1799 in the
      city of Osaka. It was reprinted from the original woodblock of 1724 edition, and
      this second edition was later used in China in 1890 as a mother copy. The first
      publication of Tongui - bogam in China was made in the year 1766. It was a
      woodblock edition printed in Kwangtung province, located in the southern end of
      China. According to the attached preface written by a high ranking official named
      Nungo, a native of Kwangtung area, the publication was originally initiated by
      the governor of that province Mr. Wang, who deeply admired the value of Tongui -
      bogam. Since the Tongui - bogam at that time was available only in Bigak, the
      palace library in Peijing, the capital of the Ch'ing dynasty, the governor Mr.
      Wang had to send a man to Peijing to make a manuscript copy of Tongui - bogam of
      25 of the volumes. But unfortunately Mr. Wang left his post before his plan to
      publish the book was realized and it was thanks to another native man named
      Chwahanmun who donated big money to cover the expenses of publication. The 1766
      edition of Tongui - bogam, one copy of which is now in the possession of Kyungbuk
      University library, is understandably not a good copy, because it has many
      erratum in it. But it was reprinted afterwards sometimes with re-engraved
      woodblock many times at various places in China. The second publication of Tongui
      - bogam in China appeared in 1890. It carries a preface written by Mincheyusang.
      It was based on the Japanese edition printed in 1799 in Oosaka. What is
      interesting with Mr. Min's preface is that it shows their deep admiration of the
      value of Tongui - bogam on one hand, and at the same time very critical attitude
      toward the basic philosophy of Hojun on the other hand.

PMID- 12192673
TI  - [History of medical ethics in Korea: focused on analysis of medical codes and
      covenants].
AB  - This article deals with the emergence of the codes of medical ethics and their
      change in Korean history. The modernized medical codes or covenants by the group
      of medical doctors has been made from the mid-twentieth century, although Korea
      has a long tradition of medical ethics, so called the Confucian medical ethics,
      Insul or Uido which were taken on very strong paternalistic characters. The
      history of the codes of medical ethics in contemporary Korea showed several
      revisions in 1961, 1965, 1979, and 1997 since the first establishment in 1955.
      Changes of political circumstances, the cultural level of the people, medical
      care system, and medical power leaded to the revisions. Throughout the revisions
      the codes or covenants of medical ethics in Korea has changed from simple
      translations of the codes by the World Medical Association and the American
      Medical Association to the reflexes of domestic medical situations; from the ones
      based on paternalistic doctor-patient relationship to more democratic ones; from
      the ones that only medical ethics were expressed to the ones that bioethics was
      expressed too.

PMID- 12192674
TI  - Subatmospheric decompression: neurological and behavioural studies.
AB  - Several studies in animals over the past decade have shown that prolonged
      exposures to pressures within the range 226 mm Hg to 160 mm Hg (30,000 to 37,500
      ft) are likely to lead to brain damage. This often results in neurological and
      behavioural disturbance, which may be subtle and reversible or gross and
      ultimately fatal. The appearance of these impairments is often delayed until
      several hours or even days after exposure. Immediate survival does not
      necessarily ensure recovery. In contrast, decompression to pressures below 160 mm
      Hg or above 226 mm Hg are unlikely to have adverse effects if the exposure is
      survived. The most probable outcomes of such decompressions are death or
      uneventful recovery.

PMID- 12192675
TI  - Otorhinolaryngological problems in medical support of space flights.
AB  - At present the main trends among the most important problems of
      otorhinolaryngology in space medicine have become defined as vestibulology,
      audiology and clinical aspects (prophylaxis, diagnosis and treatment of ENT
      diseases in flight). The principal result of recent vestibular studies has
      probably been the establishment of an apparent relationship between the
      resistance of the vestibular system to adequate ground-based stimulation and
      tolerance to space flight. The findings of the studies formed the basis for the
      development of a new system of vestibular selection, as well as demonstrated the
      usefulness of special vestibular training of astronauts by active and passive
      methods. In audiology certain urgency is acquired by the problem of noise
      limitation in space cabins and auditory system reliability prediction for
      preserving a high work capability in crew members. The hemodynamic changes in
      weightlessness, as well as the possibility for allergic lesions, create
      conditions for distorted course of the ENT diseases and vaso-motor disorders. The
      prophylaxis of aspirations also deserves close attention since the possibilities
      of their onset increase in weightlessness. The rendering of immediate, timely aid
      will depend not only on the presence of the necessary medical equipment but also
      on the ability of the crew members to render the appropriate
      otorhinolaryngological aid.

PMID- 12192676
TI  - Spacelab concept and its utilization for science.
AB  - The first part of the paper is devoted to the presentation of the Spacelab
      concepts, for which detailed design studies are at present being carried out by
      ESRO. The second part concentrates on the utilization of the Spacelab for the
      various fields of science, namely: (1) Atmospheric and space plasma physics, (2)
      Astronomy and astrophysics, (3) Material science and (4) Life sciences. The
      advantages of using the Spacelab for observations in these fields as compared to
      conventional automated satellites are highlighted.

PMID- 12192677
TI  - Prospective life-science payloads.
AB  - A viable spacelab programme is based on the thesis that biomedical specialists
      require a quantifiable, and possibly mechanistic, understanding of the
      significant changes observed in crew, in and after manned space flights. Only
      then can prophylaxis or atraumatic reversal be achieved (with potentially an
      added use to ameliorate qualitatively similar disease aspects on Earth). This
      approach could justify national funding to promote lead-up ground-based research
      as well as research and development for special equipment, of which the "spin
      off" into clinical practice could well precede its first use in Spacelab. The
      requirement for "applied expediency" arises from the watershed met early in the
      evolution of a life-sciences programme. Initially, the facility of space flight
      provoked numerous valid experiments designed to test for, or quantitate, gravity
      dependent mechanisms and their interaction with other agents, radiation,
      vibration, or absence of triggers for rhythmic patterns. In parallel, measurable
      parameters of man's function in space were being monitored, primarily to promote
      survival by remedial action when available. Monitoring data were then developed
      to find a critical mechanism feasible to testing. Often the rationale for such
      tests and experiments was that "man was there" and could, moreover, attend to
      several biological experiments in space! The watershed appeared when man in a
      Spacelab was shown as a hazard to the instrumentation, cleanliness, accuracy,
      thermal control, weight limits, etc. essential to the other disciplines. Other
      than the life sciences only the technological requirements of materials
      processing required a manned spacelab! So, life scientists have needed to rethink
      their payloads, and their constrictions, to plan for compatible load sharing. A
      composite of proposed biomedical projects related to apparently unanswered
      etiology of observed changes in returning astronauts will be used to illustrate
      the evolution of and possible answers to sample problems. The principles
      outlined, their moderation by expediency (with the untouched upon need for the
      enthusiastic involvement of biomedical potential in space projects) should remain
      our guidelines. This is in spite of the expected obsolescence of these specific
      projects within the next decade.

PMID- 12192680
TI  - Registration and reregistration application fees. Final rule; remanded for
      further notice and comment.
AB  - On October 6, 1992, Congress passed the Departments of Commerce, Justice, and
      State, the Judiciary, and Related Agencies Appropriations Act of 1993, Pub. L.
      No. 102-395, 106 Stat. 1828 (1992) (codified at 21 U.S.C. 886a) (Act). In section
      886a(3) of this Act, Congress directed that "fees charged by the DEA under its
      Diversion Control Program (DCP) shall be set at a level that ensures the recovery
      of the full costs of operating the various aspects of the (diversion control)
      program." On December 18, 1992, DEA published its proposal to adjust the existing
      registration fee schedule. 57 FR 60,148. After notice and comment, DEA published
      a Final Rule on March 22, 1993, setting the new registration fees. 58 FR 15,272.
      Following publication of the final rule, a complaint was filed by the American
      Medical Association (AMA) and others in the United States District Court for the
      District of Columbia. On July 5, 1994, the district court issued its final order
      granting the government's motion for summary judgment, and thus disposed of all
      claims with respect to all parties. American Medical Association v. Reno, 857 F.
      Supp. 80 (D.D.C. 1994). The AMA appealed. On June 27, 1995, the United States
      Court of Appeals for the District of Columbia Circuit issued its decision holding
      that DEA's rulemaking was inadequate and that the rule must be remanded, without
      being vacated, to the DEA for further proceedings in which DEA provides both an
      opportunity for meaningful notice and comment on, and an explanation of, the
      components of the diversion control program. 57 F.3d 1129 (D.C. Cir. 1995) On
      August 29, 1995, the United States Court of Appeals for the District of Columbia
      Circuit remanded this action to the district court with instructions. On November
      22, 1995, the District Court remanded the matter to DEA for proceedings
      consistent with the opinion of the United States Court of Appeals for the
      District of Columbia Circuit. This document responds to that requirement and
      provides a description of the components of the fee-funded diversion control
      program.

PMID- 12192678
TI  - Subgravity states: key to understanding the role of terrestrial gravity in human
      behaviour.
AB  - The early orbital flights, although undertaken with considerable confidence,
      involved some uncertainty because of the impossibility of simulating under
      terrestrial conditions all of the conditions encountered in space. However, space
      flight achievements by both the American astronauts and Soviet cosmonauts have
      firmly established that man, if appropriately selected, trained, and protected by
      suitable life-support systems, can perform efficiently for long periods of time
      in the hostile environment of space. We know that the side effects of vestibular
      origin pose important problems in space exploration, and the neurophysiological
      effects of any extensive, rapid adaptation processes in subgravity states have
      enabled a better understanding of man's compensatory capabilities. With the
      successful establishment of orbiting research laboratories, an unparalleled
      opportunity exists that will undoubtedly enable better understanding of the role
      played by gravity in normal terrestrial activity, not only as it affects our
      vestibular physiology, but also as it may or may not concern other systems and at
      different organizational levels in the body.

PMID- 12192679
TI  - Reflex contributions to the assessment of the vertical.
AB  - On the ground the vertical directions "up" and "down" have significance in
      relation to the strategy for avoiding collision of the skull with the planet.
      Voluntary acts to this end may be based on the experienced result of reflexly
      generated motor commands. Relevant receptors lie in the otolith organs of the
      labyrinth, but the head is seldom steady in waking life. A revised scheme of
      labyrinth reflexes on the limbs--"downhill limbs extend"--replaces the classical
      scheme of Magnus. Interactions with neck reflexes according to this scheme serve
      to stabilize the trunk. In an orbiting spacecraft the pattern of afferent signals
      from the labyrinth differs from that on the ground, and predictions based on the
      new scheme are to be tested in the project "Operation Push-Pull" proposed for
      ESRO's Spacelab. Other activities of the Council of Europe's Working Party on
      Aerospace Physiology and Medicine are briefly described.

PMID- 12192681
TI  - Using mini-rockwool blocks as growing media for limited-cluster tomato
      production.
AB  - Rockwool is an excellent growing medium for the hydroponic production of tomato;
      however, the standard size rockwool blocks [4 x 4 x 2.5 inches (10 x 10 x 6.3 cm)
      or 3 x 3 x 2.5 inches (7.5 x 7.5 x 6.3 cm)] are expensive. The following
      experiments were conducted with less expensive minirock wool blocks (MRBs), on
      rayon polyester material (RPM) as a bench top liner, to reduce the production
      cost of tomatoes (Lycopersicon esculentum) grown in a limited-cluster, ebb and
      flood hydroponic cultivation system. Fruit yield for single-cluster plants
      growing in MRBs [2 x 2 x 1.6 inches (5 x 5 x 4 cm) and 1.6 x 1.6 x 1.6 inches (4
      x 4 x 4 cm)] was not significantly different from plants grown in larger sized
      blocks (3 x 3 x 2.5 inches). When the bench top was lined with RPM, roots
      penetrated the RPM, and an extensive root mat developed between the RPM and the
      bench top. The fruit yield from plants on RPM was significantly increased
      compared to plants without RPM due to increases in fruit size and fruit number.
      RPM also significantly reduced the incidence of blossom-end rot. In a second
      experiment, single- and double-cluster plants were grown on RPM. Fruit yield for
      double-cluster plants was 40% greater than for single-cluster plants due to an
      increase in fruit number, although the fruit were smaller in size. As in the
      first experiment, fruit yield for all plants grown in MRBs was not significantly
      different from plants grown in the larger sized blocks. MRBs and a RPM bench
      liner are an effective combination in the production of limited-cluster
      hydroponic tomatoes.

PMID- 12192682
TI  - Intelligent control of a planning system for astronaut training.
AB  - This work intends to design, analyze and solve, from the systems control
      perspective, a complex, dynamic, and multiconstrained planning system for
      generating training plans for crew members of the NASA-led International Space
      Station. Various intelligent planning systems have been developed within the
      framework of artificial intelligence. These planning systems generally lack a
      rigorous mathematical formalism to allow a reliable and flexible methodology for
      their design, modeling, and performance analysis in a dynamical, time-critical,
      and multiconstrained environment. Formulating the planning problem in the domain
      of discrete-event systems under a unified framework such that it can be modeled,
      designed, and analyzed as a control system will provide a self-contained theory
      for such planning systems. This will also provide a means to certify various
      planning systems for operations in the dynamical and complex environments in
      space. The work presented here completes the design, development, and analysis of
      an intricate, large-scale, and representative mathematical formulation for
      intelligent control of a real planning system for Space Station crew training.
      This planning system has been tested and used at NASA-Johnson Space Center.

PMID- 12192683
TI  - Human characteristics of pair assembly work in a microgravity environment.
AB  - This research focuses on analyzing the human characteristics of pair assembly
      work in a microgravity environment. To obtain the necessary data, two groups of
      test subjects participated in an experiment in a pseudomicrogravity environment,
      and how such factors as work allotment, sizes of assembled objects, and
      conditions of parts influence the work efficiency were studied. The results show
      when the assembled object is smaller that it is easier to change the object's
      position and that workers can move it to an appropriate site and work easily. If
      the assembly object is attached to an object with very large mass, the work
      allotment does not result in a difference in work time. As for positioning the
      objects, step-saving processes can shorten the work time. For instance, if a part
      can be put so that both ends automatically touch the proper spots, time can be
      shortened.

PMID- 12192684
TI  - ADAPT: a predictive cognitive model of user visual attention and action planning.
AB  - We present a computational cognitive model of novice and expert aviation pilot
      action planning called ADAPT that models performance in a dynamically changing
      simulated flight environment. We perform rigorous tests of ADAPT's predictive
      validity by comparing the performance of individual human pilots to that of their
      respective models. Individual pilots were asked to execute a series of flight
      maneuvers using a flight simulator, and their eye fixations and control movements
      were recorded in a time-synched database. Computational models of each of the 25
      individual pilots were constructed, and the individual models simulated execution
      of the same flight maneuvers performed by the human pilots. The time-synched eye
      fixations and control movements of individual pilots and their respective models
      were compared, and rigorous tests of ADAPT's predictive validity were performed.
      The model explains and predicts a significant portion of pilot visual attention
      and control movements during flight as a function of piloting expertise.
      Implications for adaptive training systems are discussed.

PMID- 12192685
TI  - An integrated CMOS microluminometer for low-level luminescence sensing in the
      bioluminescent bioreporter integrated circuit.
AB  - We report an integrated CMOS microluminometer for the detection of low-level
      bioluminescence in whole cell biosensing applications. This microluminometer is
      the microelectronic portion of the bioluminescent bioreporter integrated circuit
      (BBIC). This device uses the n-well/p-substrate junction of a standard bulk CMOS
      IC process to form the integrated photodetector. This photodetector uses a
      distributed electrode configuration that minimizes detector noise. Signal
      processing is accomplished with a current-to-frequency converter circuit that
      forms the causal portion of the matched filter for dc luminescence in wide-band
      white noise. Measurements show that luminescence can be detected from as few as 4
      x 10(5) cells/ml.

PMID- 12192687
TI  - [Cardiac arrest in 2002. A new course against preventable death].

PMID- 12192686
TI  - A remote query magnetoelastic pH sensor.
AB  - A remote query magnetoelastic pH sensor comprised of a magnetoelastic thick-film
      coated with a mass-changing pH-responsive polymer is described. In response to a
      magnetic query field the magnetoelastic sensor mechanically vibrates at a
      characteristic frequency that is inversely dependent upon the mass of the
      attached polymer layer. As the magnetoelastic sensor is magnetostrictive the
      mechanical vibrations of the sensor launch magnetic flux that can be detected
      remotely from the sensor using a pickup coil. The pH responsive copolymer is
      synthesized from 20 mol% of acrylic acid and 80 mol% of iso-octyl acrylate and
      then deposited onto a magnetoelastic film by dip-coating. For a 1 micrometer
      polymer coating upon a 30 micrometer thick Metglas [The Metglas alloys are a
      registered trademark of Honeywell Corporation. For product information see:
      http://www.electronicmaterials.com:80/businesses/sem/amorph/page5_1_2.htm.] alloy
      2826MB magnetoelastic film between pH 5 and 9 the change in resonant frequency is
      linear, approximately 285 Hz/pH or 0.6%/pH. The addition of 10 mmol/l of KCl to
      the test solution decreases the sensitivity of the polymer approximately 4%.

PMID- 12192688
TI  - [Evaluation of verification of brain death and coordination with hospital organ
      procurement at the University Hospital at Lille].
AB  - OBJECTIVES: To determine the incidence of brain death (BD) and to evaluate the
      registration of potential organ donors (PD) by the organ procurement team (OPT).
      STUDY DESIGN: Two-year prospective audit in the French university hospital of
      Lille. PATIENTS AND METHODS: All deaths occurring in the intensive care units or
      the emergency department were studied. If death was consecutive to brain damage,
      on-site review of medical records and charts was performed. Death cause, presence
      of criteria for brain death and reference to the OPT were recorded for each
      death. A medical expert staff evaluated the incidence of and reasons for
      unsuitability for organ donation. After 12 months of observation, a protocol for
      "systematic alert of the OPT when brain death is suspected" was broadcast and
      evaluated during the next 12 months. RESULTS: During the first period, 277 BD
      occurred and 119 PD were suitable for organ donation. The OPT recorded 80 PD
      (67.2% of all PD) and 45 multi-organ procurements (MOP) were performed.
      Physicians opposed two major reasons for not calling OPT: anticipation of a non
      validated medical contraindication in 18 cases and approach of the family without
      the OPT team in 21 cases. After broadcast of the protocol, 110 PD were identified
      and the OPT was called in 93 cases (84.5% of all PD, p < 0.004 versus first
      period). Fifty-three MOP were performed. CONCLUSION: The OPT was not called to
      manage one-third of the PD. The protocol for "systematic alert of the OPT when
      brain death is suspected" improves the call of the OPT and increases MOP.

PMID- 12192689
TI  - [Evaluation of the demand for access to peridural obstetrical anesthesia in
      maternity units].
AB  - OBJECTIVES: This prospective study was initiated by a multicentric work. Each
      participating hospital, was asked to give data about 20 patients. Because of the
      importance of these informations for our practice, we decided to continue the
      evaluation, using the same inquiry, until 200 patients were enrolled. PATIENTS
      AND METHODS: An independent student (resident pharmacist), using a preprinted
      inquiry from interviewed two hundred consecutive in the, 48 hours after delivery
      in order to evaluate the following aspects: reasons to wish an epidural analgesia
      (EA) or not, modalities of achievement of EA. Statistical study: Chi-square and
      logistic regression. RESULTS: Among 199 analyzable files, 137 women wished for an
      EA (68.5%) but in only 90 the procedure was performed. Reasons for non
      achievement of EA were the following: labour too advanced (43/47), obstetrical
      contraindication (2/47), anaesthesiologist non available (2/47). Delay between
      arrival at hospital and EA performance was 5 h 30 during daytime and 4 h 40
      during nighttime. Delay and rate of EA achievement were not different between day
      and night time. Logistic regression analysis found following criteria related to:
      Wish for an EA analgesia: anaesthesiology consultation (OR = 193, p < 0.001),
      nulliparity (OR = 4, p < 0.002) and satisfactory information about EA (OR 35, p =
      0.051). Achievement of EA: nulliparity (OR 38, p < 0.002), length of labour (OR =
      1.01/min, p < 0.001). CONCLUSION: This study underlined the fact that one third
      of parturients do not wish for an epidural analgesia, mainly out of fear for
      neurological complications. When the obstetrician indicated an EA, our
      organisation allowed its achievement in 98% of cases. The latency between arrival
      and EA should be shortened.

PMID- 12192690
TI  - [New aspects and perspectives on cardiac arrest].
AB  - OBJECTIVES: To analyse the current knowledge based on the experimental and the
      clinical research studies focused on the main fields of cardiopulmonary
      resuscitation. DATA SOURCES: International guidelines and recent review articles.
      Data collected from the Medline database with the key word: cardiac arrest. STUDY
      SELECTION: Research studies published during the last ten years were reviewed.
      Relevant clinical information was extracted and discussed when it induced changes
      in guidelines. DATA SYNTHESIS: Promising improvements on basic and advanced life
      supports are proposed. Chest compressions prevail over ventilation. Alternatives
      to classical chest compressions are tested. Ventilatory volume must be reduced
      from 1000 to approximatively 500 mL for each breath with oxygen. Biphasic
      waveform defibrillators and automated external defibrillators will be considered
      as the best devices in the near future. Some non-catecholaminergic vasopressors
      could reduce the use of epinephrine for advanced cardiac life support. Lidocaine
      could be replaced by amiodarone as anti-arrhythmic drug of choice. New post
      resuscitation therapeutic strategies are evaluated, especially coronary
      reperfusion when the cause of cardiac arrest is cardiac. CONCLUSION: Many fields
      of cardiopulmonary resuscitation are investigated. Some relevant informations are
      included in the last international guidelines published in 2000, but most of them
      need complementary studies before other changes could be recommended for routine
      practice.

PMID- 12192691
TI  - [Inhaled nitric oxide in the peroperative period and recovery].
AB  - OBJECTIVE: To analyse the current knowledge concerning use of inhaled NO (iNO) in
      anaesthesia and intensive care. DATA SOURCE: References were obtained from
      Medline, recent review articles, the library of the department and personal
      files. STUDY SELECTION: All categories of articles on this topic have been
      selected. DATA EXTRACTION: Articles have been analysed for history, biochemistry,
      pharmacology, toxicity and clinical use of iNO. DATA SYNTHESIS: Nitric oxide (NO)
      is a potent endothelium-dependent vasodilator. Because of its selective action on
      pulmonary circulation and the lack of effect on the systemic circulation due to
      its inactivation by haemoglobin, iNO has been presented as a new therapeutic
      agent in most diseases with pulmonary hypertension. During heart transplantation
      or surgical correction of congenital heart disease, iNO decreases pulmonary
      hypertension and improves altered right ventricular function. Studies included
      however small numbers of patients. Preliminary pharmacological studies
      demonstrated that iNO was able to decrease pulmonary hypertension and improve
      systemic oxygenation in adult respiratory distress syndrome. To date, none of the
      three multicentric studies performed was able to show any significant effect on
      duration of mechanical ventilation, morbidity or mortality. Finally, the sole
      demonstrated indication for iNO which remains is the persistent pulmonary
      hypertension of the newborn. Two multicentric studies have evidenced an
      improvement in systemic oxygenation and a reduced need for extracorporeal
      membrane oxygenation. In these two studies global mortality was however
      unchanged. CONCLUSION: Persistent pulmonary hypertension is the sole demonstrated
      indication for iNO. Inhaled nitric oxide may be efficient in pulmonary
      hypertension, right ventricular dysfunction and severe hypoxemia. Inhaled nitric
      oxide must be considered as a rescue therapy or needs to be part of research
      protocols.

PMID- 12192692
TI  - [Severe retrosacral hemorrhage without bone injury following defenestration].
AB  - We describe the case of original haemorrhagic shock after a 22-year-old woman
      suicidal jumping. The first radiological evaluation showed only a non-bleeding
      fracture of the first lumbar vertebra (CT-scan) and a calcaneum fracture. Pelvic
      ring was normal. The exploration of the abdominal system (sonographic evaluation)
      did not highlight any abnormality. There was no sign of haemodynamic shock and
      the biological results were normal. Nevertheless, three hours later, severe
      haemorrhagic shock appeared without organic explanation. After new research
      (thoracic and abdominal-pelvic CT-scan), the source of bleeding was found in the
      gluteal muscles without associated pelvic ring fracture. Several vascular
      haemorrhagic failures were found on little arteries related to the internal iliac
      left artery. Haemorrhagic loss was important. Radiological gluteal arteries
      embolisation could have been realized but finally not chosen. The haemorrhage
      stopped spontaneously after about 36 hours. The early diagnosis was difficult
      because of the vertebral fracture that constrained strict dorsal position. We
      could not see the important haematoma without moving the patient. We have not
      found any description of a severe haemorrhagic shock secondary to a single blunt
      gluteal muscle.

PMID- 12192694
TI  - [Difficulties in the removal and rupture of a peridural catheter].
AB  - A case of inability to remove an epidural catheter after vaginal delivery is
      reported. Surgical removal under general anaesthesia was attempted, but the
      catheter tip was sheared off inadvertently. Because the parturient was
      asymptomatic, it was decided to stop the operation and to leave the catheter tip
      into the epidural space. This complication is often related to excessive
      insertion of the catheter into the epidural space.

PMID- 12192693
TI  - [Paraplegia and the sitting position].
AB  - The sitting position in neurosurgery may lead to complications such as air
      embolism and neurological complications. We report the case of a 16-year-old male
      who suffered from post-operation paraplegia after surgery for Arnold Chiari
      disease. This patient had several risk factors and serious morphological spinal
      abnormalities. We propose to include monitoring of somatosensory evoked
      potentials (SSEP) during this surgery in order to detect this type of devastating
      incident.

PMID- 12192695
TI  - [Fulminant mediastinitis from Streptococcus pneumoniae following cardiac
      surgery].
AB  - A 62-year-old patient was scheduled for coronary artery bypass surgery because of
      tritroncular coronary artery disease. The early postoperative period was
      uncomplicated until the 10th postoperative day when purulent fluid appeared from
      the sternal wound. Cultures of blood, wound and mediastinal tissues yielded
      Streptococcus pneumoniae with decreased susceptibility to penicillin G. Despite
      prompt surgical debridement and appropriate antibiotics, a septic shock with
      multiorgan failure occurred and the patient died on the 19th postoperative day.
      Although Streptococcus pneumoniae is uncommonly implicated in postoperative
      mediatinitis, it frequently leads to multiple organ failure and death.

PMID- 12192696
TI  - [Autoantibodies and anti-factor VIII and Chlamydia pneumoniae infection].
AB  - We report the case of a 64-year-old man without hemorrhagic history experiencing
      epistaxis. The standard hemostasis assessment including prothrombin index,
      activated partial thromboplastin time (APTT) and platelet count found an isolated
      abnormal APTT (105 sec vs 33 sec). Therefore, coagulation factors were explored.
      An acquired factor VIII deficiency (5%) with anti-FVIII antibody (4.5 Bethesda
      unit.mL-1) was recognised. This anti-FVIII antibody was related to a Chlamydia
      pneumoniae pulmonary infection. Treatment consisted of: i) Four successive
      anterior packing and activated factor VII infusion (Novoseven); ii) steroids
      injection and bi-antibiotherapy. The time course of the epistaxis was favourable
      under treatment.

PMID- 12192697
TI  - [False hyperchloremia in a bromide intoxication].
AB  - A false hyperchloremia in a patient with a history of depression suspected
      bromide intoxication. The diagnosis was confirmed by an increased bromide
      concentration > 20 mmoL.L-1. Rehydration was effective and allowed to decrease
      bromide concentration. In conclusion, hyperchloremia associated with a negative
      anion gap is a clue to the diagnosis.

PMID- 12192698
TI  - [Paracervical block: comment regarding the use of the Kobak modification].

PMID- 12192699
TI  - [Myocardial necrosis after surgery on the femoral artery: failure to cease
      platelet inhibitors?].

PMID- 12192700
TI  - [Anesthesia-resuscitation and the law: elements for understanding the guidelines
      of the SFAR].

PMID- 12192701
TI  - [Medication and the third world: a challenge for all].

PMID- 12192702
TI  - [Vietnam: infectious entities of yesteryear and advances toward a modern
      society].

PMID- 12192703
TI  - [Noma: past, present and future?].

PMID- 12192704
TI  - [Mecca: health advisory for pilgrims].

PMID- 12192706
TI  - [Scytalidium infections].

PMID- 12192705
TI  - [Menomune: a tetravalent vaccine for the prophylaxis of meningococcal infections
      of types A, C, W135, Y].

PMID- 12192707
TI  - [Third edition of the Principal Hospital of Dakar meeting days ].

PMID- 12192708
TI  - [Clinical, bacteriological and therapeutic aspects of meningococcal meningitis in
      Dakar in 1999].
AB  - Two major outbreaks of meningitis due Neisseria meningitidis serogroup A occurred
      in Senegal in 1998 and 1999. The purpose of this report is to describe clinical,
      bacteriological and therapeutic findings in 70 patients admitted for
      cerebrospinal meningitis to the Infectious Disease Clinic at the Fann University
      Teaching Hospital in Dakar in 1999. Diagnosis was based on direct microscopic
      examination after Gram staining in 71% of the cases, culture in 76%, and
      detection of soluble antigens in cerebrospinal fluid in 24%. Median patient age
      was 20 years. The highest incidence, i.e. 66% of cases, was recorded during
      February, March and April. Meningitic syndrome and fever were observed with 86%
      of the cases. The average duration of antibiotic therapy was 8 days.
      Chloramphenicol was the most commonly used drug (84% of cases). All strains
      identified in cultures were sensitive to chloramphenicol, ceftriaxone and
      cefotaxime but resistant to cotrimoxazole. Outcome was favorable in 93% of the
      cases. Three patients (4%) died and two (3%) developed hearing loss. Despite the
      low death rate in this series of patients treated in a hospital setting, mass
      vaccination is still the most effective mean of controlling meningococcal
      meningitis.

PMID- 12192709
TI  - [Center of multidrug-resistant malaria in a forest zone of Cameroon revisited
      after 14 years].
AB  - In vitro sensitivity of Plasmodium falciparum to chloroquine, amodiaquine,
      quinine and pyronaridine was assessed using the DELI microtest method in 2000.
      Isolates were collected on the La Nye'ete rubber plantations located in a forest
      zone 45 km southeast of Kribi, Cameroon. Comparison with results of the last
      survey in 1986 showed that chloroquine resistance has remained stable (61% versus
      56%). Sensitivity to amodiaquine and pyronaridine was high (76.5% and 89.5%
      respectively) in all isolates including chloroquine-resistant isolates. Despite
      intensive use in the area, quinine remained highly effective (sensitivity, 80%).
      These results indicate that chloroquine sensitivity has remained relatively
      stable in this resistant zone and that little cross-resistance with amodiaquine
      and pyronaridine has developed. These findings hold the promise for an
      alternative treatment of uncomplicated Plasmodium falciparum malaria in
      chloroquine-resistance areas.

PMID- 12192710
TI  - [Contribution of computerized tomography in the diagnosis of cerebrovascular
      accidents in Nouakchott, Mauritania].
AB  - This prospective study was focused on the radiological features of stroke and the
      recent contribution of computerized tomographic scan (CT scan) to diagnosis of
      hospitalized stroke patients. All patients admitted for stroke to the Neurology
      Department of the Nouakchott Hospital between January 1, 1996 and June 30, 1997
      were enrolled in this study. Patients were divided into two groups, i.e. CT group
      including patients that underwent CT scan during hospitalization and control
      group including patients that did not undergo CT scan for financial reasons. The
      etiology of stroke (35.1% of hospitalizations) was ischemic in 52% of cases and
      hemorrhagic in 48%. There were more men than women and mean age was 60 years for
      ischemic stroke versus 56 years for hemorrhagic stroke. Only 8% of patients
      presented documented diabetes. Deep infarction accounted for 52% of ischemic
      stroke including large-artery infarction in 61.2% and lacunar infarction in
      38.8%. Superficial infarction usually involved the territory supplied by the
      superficial sylvian artery. Intraparenchymal hematomas accounted for 78% of
      hemorrhagic strokes in relation with the high incidence of arterial hypertension
      (65.2%). The most common locations were capsulo-lenticular (55%) and capsulo
      thalamic (39%). Stroke-related mortality was high (20.3%) especially in patients
      presenting prolonged disturbances of consciousness and renal insufficiency. By
      allowing more accurate assessment of lesions, CT-scan improved patient management
      and therapeutic outcome.

PMID- 12192711
TI  - [Atypical neurosyphilis: 28 cases observed at the University Hospital Center of
      Conakry].
AB  - This study describes a series of 28 cases of neurosyphylis presenting atypical
      oligosymptomatic syndromes involving epileptic attack, chronic headache,
      peripheral facial paralysis, deafness, isolated optic atrophy, and cerebral
      ataxia. Diagnosis was based on positive results (VDRL-TPHA) of serological
      reactions in blood samples and analysis of cerebrospinal fluid showing
      pleocytosis (mean lymphocyte level, 69%) and elevated protein levels. Epilepsy
      and chronic headache were the most common clinical manifestations. Brain scan
      demonstrated low-grade ventricular dilatation associated with nonspecific
      cerebral atrophy in 8 cases and isolated cerebral atrophy in three. In the
      remaining 17 cases brain scans were normal.

PMID- 12192712
TI  - [Peripheral blood culture as a diagnostic modality for visceral leishmaniasis:
      apropos of 61 cases].
AB  - The purpose of this prospective study was to assess the efficacy of culture of
      peripheral blood samples on NNN medium for detecting Leishmania. A total of 61
      peripheral venous blood samples were tested. Most samples were collected from
      immunocompetent children presenting visceral leishmaniasis. The sensitivity of
      peripheral blood culture was 61%. Concordance with conventional bone marrow
      culture was good but the marrow technique was quicker. Since it is minimally
      invasive and easy to perform, peripheral blood culture is an attractive
      diagnostic alternative in immunocompetent patients. In addition peripheral blood
      culture presents a major epidemiological advantage in allowing identification of
      the causative strain of Leishmania if bone marrow culture was not performed for
      isoenzymatic characterization.

PMID- 12192713
TI  - [Diluted injectable quinine in the intramuscular and intrarectal route:
      comparative efficacity and tolerance in malaria treatment for children ].
AB  - The intramuscular (i.m.) route is generally used for treatment of childhood
      falciparum malaria in outlying health care units in Togo. The purpose of this
      randomized therapeutic trial was to compare the efficacy and tolerance of diluted
      injectable quinine administered by the i.m. versus intrarectal (IR) route. A
      total of 64 children ranging in age from 8 months to 15 years were treated, i.e.
      32 for each administration route. All children presented uncomplicated falciparum
      malaria in association with vomiting in 30 cases, a single unrecurring seizure
      with postictal coma lasting less than 30 minutes in 25 patients, or prostration
      without neurological manifestations in 9. Injectable quinimax (an association of
      cinchona alkaloids) was diluted to a concentration of 60 mg base/ml for i.m.
      injection into the thigh and 30 mg base/ml for use by the IR route.
      Administration was performed every 12 hours for 72 hours at a dose of 12.5 mg/kg
      for patients in the i.m. group or at a dose of 15 mg/kg in the IR group. The anus
      and lower rectal mucosa were examined using an anal valve before and after
      treatment using the IR route. Analysis of mean temperature curves demonstrated no
      significant difference between the clinical effectiveness of quinimax
      administered by the i.m. versus IR route (p > 0.05). Similar effect were also
      observed on parasitemia which disappeared completely in all patients by the end
      of the 72-hour treatment. The main problems were insufficient product retention
      requiring re-administration in 25% of patients in IR group and residual pain at
      the injection site in 12.5% of patients in the i.m. group. Endoscopic examination
      revealed no evidence of ulceration or necrosis of the anorectal mucosa. These
      findings indicate that administration of diluted injectable quinine by IR route
      is an effective, well-tolerated alternative for treatment of childhood falciparum
      malaria. It should be used preferentially in outlying health care units in
      patients presenting severe malaria pending transfer to an hospital, or signs of
      "intermediate severity" such as hyperpyrexia, hyperparasitemia, unrepeated
      seizure, or intensive vomiting.

PMID- 12192714
TI  - [Laryngeal papillomatosis: value of early diagnosis, apropos of 7 cases diagnosed
      at the University Hospital Center in Brazzaville, Congo].
AB  - Laryngeal papillomatosis is a benign tumor process that occurs most commonly in
      children but can also affect adults. The purpose of this report is to describe a
      series of 7 cases treated at the Otorhinolaryngology Department of the University
      Hospital Center in Brazzaville, Congo. Special focus is placed on particularities
      and pitfalls of management. There were 4 girls and 3 boys with a mean age of 8.4
      years (range, 7 to 10 years). The mean duration between the onset of symptoms and
      diagnosis was 3.4 years (range, 1 to 5 years). The initial symptom was choking in
      3 cases, hoarseness in 2, and combined choking and hoarseness in 2. Tracheotomy
      was required in 3 cases. Instrumental debulking was performed in all cases. Two
      patients died due to obstruction of the cannula. Outcome was favorable in the
      remaining 5 cases. Our experience highlights the need for early diagnosis for
      optimal therapeutic outcome. In this regard information campaigns are necessary
      to educate doctors and parents.

PMID- 12192715
TI  - [Ainhum and pseudoainhum: clinical aspects and etiopathogenic hypotheses].
AB  - Pseudoainhum is a rare acquired or congenital disorder characterized by
      progressive development of a fibrotic band on a finger or toe until spontaneous
      autoamputation occurs. Ainhum is an idiopathic disease involving the fifth toes
      of black people mainly in tropical zones. Based on experience in five cases and a
      review of the literature, the authors describe clinical features of these
      diseases and analyze various etiological hypotheses including infectious
      (mycosis, mycobacteria), traumatic (plants), vascular (andysplasia), neurological
      (polyneuritis), and genetic (keratodermia) mechanisms.

PMID- 12192716
TI  - [Tuberculosis and HIV infection: experience of the national tuberculosis
      prevention program in Djibouti: 1990-1996].
AB  - Based on analysis of data collected from the national tuberculosis prevention
      program in Djibouti between 1990 and 1996, the authors analyzed the relationship
      between HIV infection and tuberculosis. The study cohort comprised a total of
      22,000 patients including 14,000 with documented HIV infection. Although HIV
      infection probably worsened the situation, it was neither the only nor the main
      factor involved in the resurgence of tuberculosis. Demographic growth, higher
      population density, and increasing poverty as well as the quality of the national
      tuberculosis prevention program must be taken into account. The incidence of
      smear-negative tuberculosis was not significantly higher in HIV-infected patients
      (incidence of smear positive cases, > 92%). Extrapulmonary tuberculosis
      especially of pleural involvement was more common (15% versus 9.4%). Treatment
      was effective in HIV-infected patients. If directly observed (DOT) therapy was
      used, there was no risk of emergence of multidrug-resistant tuberculosis strains.
      Drug side-effects associated with the protocols used in Djibouti were not greater
      in HIV-infected patients. Most additional mortality observed in HIV-infected
      tuberculosis patients (10.5% versus 2%) was due to progression of HIV infection.

PMID- 12192717
TI  - [Snake envenomation in French Guiana].
AB  - French Guiana is a French Overseas Department in South America. Ninety-five
      percent of the territory is a tropical rainforest. Its rich fauna includes seven
      families of snakes but only 3 are potentially venomous. Less than 12% of species
      and, depending on biotope, 10 to 30% of specimens collected are dangerous for
      humans. The annual incidence of snakebite is less than 50 bites per 100,000
      inhabitants overall but increases to 600 per 100,000 for persons active in the
      rainforest where the risk is highest. The most common envenomation by Viperidae
      such as Bothrops, which is abundant throughout French Guiana, induces
      inflammation, necrosis and hemorrhage. Crotalus durissus, a rattlesnake living in
      coastal savannah, or Micrurus sp cause neuromuscular poisoning. Coral snakes are
      encountered throughout French Guiana, but envenomation is very rare. Antivenom
      therapy must be administered by the intravenous route in association with
      symptomatic treatment and, if necessary, resuscitation in a specialized care
      unit.

PMID- 12192718
TI  - [Fluoroquinolones in children].
AB  - The only currently recommended pediatric use of fluoroquinolones involves
      ciprofloxacine for treatment of pyocyanic infection in children with cystic
      fibrosis. The main contraindication for use of fluoroquinolones in children is
      arthrotoxicity. Notwithstanding they are occasionally used for serious infections
      when there is no other therapeutic alternative. In addition to cystic fibrosis,
      potential pediatric indications include multidrug-resistant salmonella and
      shigellosis, certain enterobacterial infections in newborns, complicated urinary
      tract infections, and severe multidrug-resistant bacterial infection especially
      in immunocompromised subjects. The availability of new quinolones against
      pneumococcus should have little impact on current therapeutic strategies for
      upper or lower respiratory tract infections since potential indications in
      children are limited. However when the new generation reaches the market,
      fluoroquinolones should offer new alternatives for treatment of penicillin
      resistant pneumococcal meningitis. Studies comparing children and adults have
      shown that arthrotoxicity is approximately the same or only slightly higher. The
      main problem for assessment of adverse effects is that pediatricians often fail
      to report the limited number of cases in which fluoroquinoles have been
      prescribed. Regardless fluoroquinolones must remain a second or third line agent
      for treatment of severe infection in cases in which no other alternative
      especially by the oral route is available. Use must be restricted to situations
      in which the risks are outweighed by potential benefits. Limiting pediatric use
      will slow down the emergence of resistant bacteria.

PMID- 12192719
TI  - [Treatment of noma].
AB  - Noma is a disease specific to developing countries. Early antibiotic treatment
      can stop disease progression. Surviving patients may present disfigurement with
      functional and cosmetic sequels. The purpose of this report is to describe
      treatment of active disease and its sequels. Treatment of defects requires
      reconstructive surgery. Surgical modalities depend on the extent and location of
      lesions, available technical facilities and surgeon skill. Various flap
      techniques can be used ranging from simple flaps and autoplasty to complex
      procedures involving microsurgery.

PMID- 12192720
TI  - [What are incidence and prevalence].
AB  - Morbidity indicators are basic tools of epidemiology. In this short technical
      presentation, examples from tropical medicine are used to illustrate and explain
      the concepts of incidence, incidence rate, cumulative incidence or attack rate,
      incidence density rate, prevalence, prevalence rate and the link between disease
      prevalence and incidence.

PMID- 12192721
TI  - [Franco-Vietnamese military cooperation in the field of malaria].
AB  - In 1991 after the long period of strife the international community moved on
      deploying a program for malaria control in Vietnam. At that time epidemiological
      surveys documented one million cases a year including 4 to 5,000 fatalities. This
      was the starting point for a military and defense cooperation program between the
      Vietnamese Army Health Corps and the Tropical Medicine Institute of the French
      Army Health Corps (French acronym, IMTSSA). The IMTSSA has the full range of
      expertise to train therapists, epidemiologists and research workers as well as to
      perform detection and pharmacological study of drug-resistant malaria strains.
      Between 1996 and 2002, the IMTSSA sent various specialists to Vietnam within the
      framework of this program. These specialists have not only established state-of
      the-art technical facilities for epidemiological surveys and biological research
      but also trained Vietnamese specialists to perform these duties. This program has
      contributed to controlling malaria in Vietnam. Further development is needed to
      coordinate the exchange of data necessary to continuously monitor the efficacy of
      control measures in Southeast Asia where the incidence of strains resistant to
      most currently used antimalarials has been increasing sharply.

PMID- 12192722
TI  - [Severe choleriform diarrhea from Plesiomonas shigelloides in an expatriate from
      Djibouti].

PMID- 12192723
TI  - [Leptospirosis microepidemic in Martinique].

PMID- 12192724
TI  - [Multiple candidiasis in an HIV+ patient. Apropos of 1 case].

PMID- 12192725
TI  - [Effect of shade on mosquito reproduction in drainage ditches at Lwiro, province
      of Sudkivu, Democratic Republic of the Congo].

PMID- 12192726
TI  - [Huntington's disease, towards the end of neuronal death?].

PMID- 12192727
TI  - [Medical ethics, a counter-weight to the logics of the Perruche decree].
AB  - FROM A CONTRACTUAL LOGIC TO A PROBABILISTIC APPROACH: Since 1936, reflections on
      the relationship between the physician and the patient have progressed within the
      context of a contractual legal concept. Its contents have been based more on
      jurisprudence than on the physicians' reflections with regard to their practice.
      Associated with this contractual logic, some confusion exists between a lesion, a
      medical concept, and a handicap, which is the social consequence of one's status
      of health. This has been reinforced by the scientific progress made in medicine,
      which privileges a probabilistic approach based on scientific data, rather than
      the uncertainty, inscribed in the dialogue and singularity of the encounter.
      REGARDING THE PERRUCHE DECREE: We analyzed the reports submitted to the court of
      cessation regarding the Perruche affair, together with the first chapter of the
      law concerning the rights of the patients and the quality of health system, by
      studying the extent to which this decision was inscribed or not in the continuity
      of past legal decisions, and whether the characteristics described above were
      present. In this decree, the predominating contractual logic is that the notion
      of handicap is not analyzed, and the scientific and probabilistic conception of
      medical practice is involved in the debate. THE NECESSITY FOR REFLECTION: Our
      discussion insists on the necessity of constructing a reflection on the medical
      presentation; society cannot accept that this be reduced to the strict respect of
      the elements of the contract, defined by legal decisions. It should be carefully
      thought out by health professionals, and in collaboration with human science.

PMID- 12192728
TI  - [Evaluation of medical semiology teaching and teachers. Study of student
      satisfaction in the second cycle first year].
AB  - OBJECTIVE: To know the students' opinion concerning semiology teaching and
      teachers. METHODS: Annual enquiry between 1990-91 and 2000-01, before and after a
      reform increasing to 400 the hours dedicated to medical clerkships in the second
      and third years of the courses. RESULTS: Before the reform, at least 62% of the
      students were in favor of the general organization, while a growing percentage
      (reaching 79.6%; p < 0.0001) considered the number of hours dedicated to clinical
      clerkship as insufficient. Concerning the teachers, the assessment concerning the
      "assistant heads of departments" (AHD) showed great disparities. Out of 100
      teachers-year, 4 obtained a score lesser than 10/20 and 59 greater than 15/20.
      After the reform, 19 AHD out of 33 obtained more than 15/20 and 5 less than
      10/20. The reintroduction of lectures was not criticized. The professors who gave
      lectures were reproached by the students for delaying them or for not having
      given them at all. They were also reproached for their lack of relationship with
      the teaching objectives. The scores allocated to professors ranged from 4.5 to
      15.9/20. CONCLUSION: Enhancing the value of teaching for an AHD's university
      career and reducing the administrative burden for all teachers would be useful to
      improve medical education, especially in semiology.

PMID- 12192729
TI  - [Remembering to manage hyperglycerolemia in atypical hypertriglyceridemia].

PMID- 12192730
TI  - [Antioxidants to slow aging, facts and perspectives].
AB  - FREE RADICALS AND THE THEORY OF AGING: Severe oxidative stress progressively
      leads to cell dysfunction and ultimately cell death. Oxidative stress is defined
      as an imbalance between pro-oxidants and/or free radicals on the one hand, and
      anti-oxidizing systems on the other. The oxygen required for living may
      indirectly be responsible for negative effects; these deleterious effects are due
      to the production of free radicals, which are toxic for the cells (superoxide
      anions, hydroxyl radicals, peroxyl radicals, hydrogen peroxide, hydroperoxides
      and peroxinitrite anions). Free radical attacks are responsible for cell damage
      and the targeted cells are represented by the cell membranes, which are
      particularly rich in unsaturated fatty acids, sensitive to oxidation reactions;
      DNA is also the target of severe attacks by these reactive oxygen species (ROS).
      THE DEFENCE SYSTEMS: These are represented by the enzymes and free radical
      captors. The latter are readily oxidizable composites. The free radical captor or
      neutralization systems of these ROS use a collection of mechanisms, vitamins (E
      and C), enzymes [superoxide dismutase (SOD), glutathion peroxidase (GPx) and
      others], and glutathion reductase (GSH), capable of neutralizing peroxinitrite.
      The efficacy of this system is dependent on the genome for the enzymatic defence
      systems, and on nutrition for the vitamins. Some strategies aimed at reducing
      oxidative stress-related alterations have been performed in animals. However,
      only a few can be used and are efficient in humans, such as avoidance of
      unfavourable environmental conditions (radiation, dietary carcinogens,
      smoking...) and antioxidant dietary supplementation. DIETARY SUPPLEMENTATION:
      Epidemiological data suggest that antioxidants may have a beneficial effect on
      many age-related diseases: atherosclerosis, cancer, some neurodegenerative and
      ocular diseases. However, the widespread use of supplements is hampered by
      several factors: the lack of prospective and controlled studies; insufficient
      knowledge on the pro-oxidant, oxidant and ant-oxidant properties of the various
      supplements; growing evidence that free radicals are not only by-products, but
      also play an important role in cell signal transduction, apoptosis and infection
      control. RECOMMENDATIONS: Although current data indicate that antioxidants cannot
      prolong maximal life span, the beneficial impact of antioxidants on various age
      related degenerative diseases may forecast an improvement in life span and
      enhance quality of life. The current lack of sufficient data does not permit the
      systematic recommendation of anti-oxidants. Nevertheless, antioxidant-rich diets
      with fruit and vegetables should be recommended.

PMID- 12192731
TI  - [Physical activity to delay the effects of aging on mobility].
AB  - SARCOPENIA: Aging is accompanied by the progressive reduction in cardio-pulmonary
      capacity and muscular strength. These two phenomena are partly related to the
      decrease in muscle mass, or sarcopenia. CARDIO-PULMONARY CAPACITY: Measured by
      maximum oxygen consumption (VO2max), it demonstrates the individual's capacity
      for movement. It is also the principle marker of mortality due to cardiovascular
      events. VO2max decreases by around 0.8% each year, in close correlation with the
      evolution in muscle mass. These phenomena are partly related to reduced physical
      activity and, particularly, intense activity greater than 6 MET. Regular practice
      of moderately intense physical activity can maintain VO2max at a level 20 to 35%
      superior to that of the mean level in the same age range, and is associated with
      increased autonomic nervous system activity. DECREASED MUSCULAR STRENGTH:
      Sarcopenia and the proportional decrease in fast-twitch muscle fibers are related
      to a reduction in physical activity. The decrease in muscular strength is a
      handicapping factor and increases the risk of falls. Two sessions of training per
      week can increase by more than 30% the strength of the muscles concerned, by
      increasing the muscle volume and the maximum frequency of emission of motoneuron
      influx. The production of somatotropin, insulin-like growth factor-I and
      testosterone can also be increased. High-resistance exercises are themselves
      sufficient to increase bone density. In the light of these advantages, the
      practice of workouts in endurance and strength should be encouraged.

PMID- 12192732
TI  - [Alpha-2 adrenergic receptors and Parkinson's disease].

PMID- 12192733
TI  - Spontaneous adverse event signaling methods: classification and use with health
      care treatment products.
AB  - AE signal detection and its techniques are part of the continuum of public health
      surveillance, borrowing from both its theory and application (171). Like public
      health surveillance networks, whose major goals are to identify early signs of
      new outbreaks, pinpoint new organisms, and monitor designated illnesses, AE
      signaling and surveillance systems attempt to provide early warnings of
      previously unsuspected product-AE pairs, hypothesize potential drug-event
      relations, identify populations "at risk," and facilitate case ascertainment and
      definition. In both examples, definitive research is often subsequently
      undertaken to quantify the strength of relations that may be proposed. As with
      any public health surveillance effort, AE surveillance provides an infrastructure
      for the ongoing collection of health data and its direct integration into the
      health regulatory policy (172), including its keystone role in risk assessment
      and management. However, unlike many surveillance systems, postmarketing AE
      systems collect case information that is often relatively incomplete and
      imperfect, estimate exposure based on surrogate values (e.g., sales data), and
      are used by both governmental and the private sector for preventive planning.
      These factors make AE signaling and surveillance more ambiguous, regulatory
      oriented, and complex than its disease counterparts (173). Despite such issues,
      AE signaling methods continue to evolve in extent, complexity, and acceptance (4,
      131, 174). Undoubtedly, this is largely due to the widespread practical
      experience that has been gained with spontaneous reporting systems over the past
      4 decades and the cumulative usefulness that has been demonstrated.

PMID- 12192734
TI  - Participation of lycopene and beta-carotene in carcinogenesis: defenders,
      aggressors, or passive bystanders?

PMID- 12192735
TI  - Toxic oil syndrome: the perspective after 20 years.
AB  - Toxic oil syndrome burst upon the scene in Spain in May of 1981, draining the
      resources of a newly evolving political and social medicine system. The vehicle
      of the causative toxic agent was identified as an illicit oil that had been
      diverted from industrial use and refined in order to remove the aniline
      denaturant, and that was sold in unlabeled 5-liter containers by itinerant
      salesmen. Over 20,000 people were ultimately affected, and over 1,200 deaths from
      all causes have been recorded in the affected cohort. The epidemiologic
      investigation of toxic oil syndrome involved all facets of investigative and
      analytical work; from visits to factories and interviewing workers, to
      sophisticated chemical and statistical analytical techniques. This investigation
      serves as a further illustration that data and information of all types, and from
      a wide range of fields, need to be systematically collected and evaluated in
      order to best resolve an epidemiologic mystery. Astute clinical observation of
      the patients, however, led to the hypothesis that toxic oil syndrome was a result
      of a toxic exposure. In this and other epidemics of unknown etiology, clinical
      observation and the intense scrutiny of patients' histories, signs, and symptoms
      by treating clinicians have often led to hypotheses that could be tested
      epidemiologically. When there are medical unknowns, the role of the astute
      clinician continues to be crucial. The toxic oil syndrome epidemic is an example
      of how even a developed country can be affected by a massive epidemic of
      environmental origin if failures occur in the systems that control and regulate
      the food supply or other consumer products. However, such failures could occur
      anywhere that large commercial networks operate on the regulatory edge, and if
      these business lack an in depth knowledge of the consequences of alterations in
      manufacturing conditions. Such was the case with eosinophilia-myalgia syndrome as
      well, when apparently minor alterations in manufacturing conditions of L
      tryptophan led to an increase in impurities in the product that were later
      associated with the illness. These risks are even greater in countries with few
      or inconsistent control systems, making the food and drug supply potential
      portals of entry for serious health hazards, as is further exemplified by the
      tragic episode of pediatric renal failure in Haiti associated with a legitimate
      consumer product, paracetamol elixir, that had been manufactured using a
      fraudulently supplied toxic ingredient, diethylene glycol (81). The potential
      toxicants in the adulterated rapeseed oil were present in extremely small
      amounts. If fatty acid anilides or related compounds are indeed the etiologic
      agents in toxic oil syndrome, then these compounds must be extremely toxic at the
      parts per million concentrations at which they were found. Further, the roles of
      causative agents in the development of disorders such as scleroderma,
      eosinophilic fasciitis, eosinophilic perimyositis, and other similar diseases are
      unknown, but scientists can speculate that some sort of low level environmental
      agent may play a role if such extremely small quantities of contaminants are
      indeed capable of causing disease. Although the exact identity of the etiologic
      agent in toxic oil syndrome remains unknown, work on toxic oil syndrome
      continues. Follow-up clinical studies and long-term mortality studies are under
      way. Investigation of the mechanisms involved in toxic oil syndrome continues.
      The identification of suspect chemical compounds, their characterization, and
      effects will hopefully one day contribute to the prevention of other similar
      diseases.

PMID- 12192736
TI  - Epidemiologic evidence linking antioxidant vitamins to pulmonary function and
      airway obstruction.

PMID- 12192737
TI  - Diet and obstructive lung diseases.
AB  - The results presented in this review suggest that the impact of nutrition on
      obstructive lung disease is most evident for antioxidant vitamins, particularly
      vitamin C and, to a lesser extent, vitamin E. By decreasing oxidant insults to
      the lung, antioxidants could modulate the development of chronic lung diseases
      and lung function decrement. Antioxidant vitamins could also play an important
      role in gene-environment interactions in complex lung diseases such as childhood
      asthma. Data also suggest that omega-3 fatty acids may have a potentially
      protective effect against airway hyperreactivity and lung function decrements;
      however, relevant data are still sparse. Although epidemiologic data suggest that
      consumption of fresh fruit may reduce risk of noncarcinogenic airway limitation,
      there are no clear data on which nutrients might be most relevant. While some
      studies evaluate daily intake of vitamin C, other studies use fruit consumption
      as a surrogate for antioxidant intake. Given the dietary intercorrelations among
      antioxidant vitamins, particularly vitamin C, beta-carotene, and flavonoids, as
      well as other micronutrients, it may be difficult to isolate a specific effect.
      Some population subgroups with higher levels of oxidative stress, such as
      cigarette smokers, may be more likely to benefit from dietary supplementation,
      since some studies have suggested that antioxidant intake may have a greater
      impact in this group. Studies of lung function decrement and COPD in adults
      suggest that daily intake of vitamin C at levels slightly exceeding the current
      Recommended Dietary Allowance (60 mg/day among nonsmokers and 100 mg/day among
      smokers) may have a protective effect (20). In the Schwartz and Weiss (85) and
      Britton et al. (87) studies, an increase of 40 mg/day in vitamin C intake led to
      an approximate 20-ml increase in FEV1. Daily mean vitamin C intakes in these
      studies were 66 mg and 99.2 mg, respectively, and the highest intake level (178
      mg/day) was approximately three times the Recommended Dietary Allowance. Although
      the amplitude of the effect was modest, if these effects accumulate over 20-30
      years, they could have a meaningful impact on the rate at which pulmonary
      function declines, particularly in symptomatic subjects (85). Longitudinal data
      support the hypothesis that fresh fruit consumption has a beneficial impact on
      the lung (95). Among children, consumption of fresh fruit, particularly fruit
      high in vitamin C, has been related to a lower prevalence of asthma symptoms and
      higher lung function (64). This effect was observed event at low levels of fruit
      consumption (one or two servings per week vs. less than one serving per week),
      which suggests that a small increase in dietary intake could have a beneficial
      effect. Consumption of fish has also been related to lower airway hyperreactivity
      among children (75) and higher lung function in adults (100); however,
      longitudinal data do not provide evidence that increased omega-3 fatty acid
      intake protects against lung disease (101). Experimental studies of persons with
      asthma suggest that magnesium infusion may have a place in the acute treatment of
      asthma, but it does not seem to have long-term benefits. The studies of sodium,
      selenium, and fish oils do not show convincing evidence of clinical benefits.
      Studies of vitamin C supplementation suggest a short-term protective effect on
      airway responsiveness and pulmonary function. It remains to be proven whether
      consistent use of vitamin C would have a protective effect on the evolution of
      chronic asthma. Results from supplementation studies conducted among subjects
      exposed to high levels of oxidants (57-60) suggest that daily intake of
      antioxidant vitamins exceeding the Recommended Dietary Allowance may have a
      beneficial effect on lung airways and that intake higher than the Recommended
      Dietary Allowance should be recommended for populations chronically exposed to
      photooxidant air pollutants (such as ozone), cigarette smoking, or vigorous
      exercise. It is difficult to determine the amounts of antioxidant vitamins that
      people should consume. In particular, although vitamin C was shown to have
      maximum bioavailability when given in a single dose of 200 mg (102), experiments
      on which this finding was based were conducted under normal conditions.
      Guidelines from the US National Cancer Institute (103) recommend consumption of
      five servings of fruit and vegetables daily, corresponding to a vitamin C intake
      exceeding 200 mg. Dietary surveys carried out in the US population indicate that
      less than 12 percent of US children and adults meet this recommended level of
      intake (104). Diet appears to be an important cofactor in the development of
      obstructive lung disease, although data are still sparse. There is a need for
      further research in experimental and epidemiologic settings to better understand
      the physiologic effects of antioxidant vitamins, omega-3 fatty acids, and other
      nutrients on lung tissues. The impact of diet on the incidence and evolution of
      asthma and COPD should be investigated using a cohort design that accounts for
      known risk factors. This will allow researchers to evaluate the exposure-disease
      relation over an adequate time frame and obtain insight into the causality of the
      relation. Some of these studies should enroll infants and young children to
      determine the impact of early diet on respiratory health. Research should also
      focus on the equally challenging policy issues--namely, finding effective methods
      of convincing people to increase their daily consumption of fresh fruits and
      vegetables, to stop smoking cigarettes, and to minimize their environmental and
      occupational exposure to pollutants and other agents that cause respiratory
      disease.

PMID- 12192738
TI  - From exposure to disease: the role of environmental factors in susceptibility to
      and development of tuberculosis.

PMID- 12192739
TI  - Association between hepatitis C virus infection and diabetes mellitus.

PMID- 12192740
TI  - Height, leg length, and cancer risk: a systematic review.

PMID- 12192741
TI  - Gender gap in longevity and disability in older persons.

PMID- 12192742
TI  - Comparison of sun protection behaviors among physicians and patients.
AB  - Sun protection behaviors were compared between 100 patients and 85 physicians in
      a university-based clinic and hospital. Physicians were more likely to use
      sunscreen, but patients were more likely to wear long sleeve shirts and stay in
      the shade to avoid the sun. There was no statistically significant difference in
      the frequency or number of sun protection behaviors utilized.

PMID- 12192743
TI  - Examination of the temporal relationship between smoking and major depressive
      disorder among low-income women in public primary care clinics.
AB  - PURPOSE: To determine the prevalence of major depressive disorder (MDD) by
      smoking status, and the temporal relationship between smoking and MDD, and
      explore other smoking-related variables that may be associated with MDD. DESIGN:
      Cross-sectional study. SETTING: Public primary care clinics. SUBJECTS:
      Researchers studied 338 women (76% African-Americans) who were randomly selected
      while attending appointments in two public primary care clinics. MEASURES: Data
      pertaining to smoking-related variables and MDD diagnosis were obtained using the
      Diagnostic Interview Schedule for the Diagnostic Statistical Manual of Mental
      Disorder IV (DSM-IV). RESULTS: The prevalence of a lifetime history of MDD was
      significantly higher for current smokers (56.6%) than among former smokers
      (37.5%) or never-smokers (30.3%; p < .001). Most ever-smokers (81.3%) began
      smoking and were nicotine-dependent (63.6%) prior to their first episode of MDD.
      Using logistic regression, after controlling for demographic and smoking-related
      variables, age of smoking onset was the strongest variable associated with MDD
      among ever-smokers. Specifically, the odds of having an MDD decreased by 8.2% for
      each year delay in smoking initiation. CONCLUSION: These results suggest that
      smoking initiation precedes MDD and that smoking is associated with a high
      prevalence of MDD among low-income women attending primary care clinics. Further,
      the younger women start smoking the more likely they are to have MDD.

PMID- 12192744
TI  - Using ethnography to improve intervention design.
AB  - PURPOSE: The purpose of this research was to use a three-phase ethnographic
      approach to examine the range of factors that affect people's decisions about
      physical activity and diet. DESIGN: We used open-ended data collection
      strategies, analyzed inductively, to inform, the development of a family
      intervention. SETTING: The study was conducted in a small low-income town in
      Colorado. SUBJECTS: Families with young children were selected to include social,
      economic, and ethnic diversity. Twenty-nine of 31 invited families participated
      (94%). MEASURES: The measures consisted of 21 open-ended interviews in the first
      phase; 12 semistructured interviews in the second phase, and six home visits in
      the third phase. The Atlas.ti program25 was used for data analysis. RESULTS:
      Significant barriers to regular exercise and good dietary habits were grouped as
      social/structural (e.g., working parents, costs of exercise) and cultural (e.g.,
      perception that fast food is normal). Behavioral facilitators include disease in
      the family and community opportunities for exercise. Results revealed family
      values and dynamics that other methods would have missed. CONCLUSIONS: These data
      suggest that families are embedded in a multicomponent "web" of factors that
      influence diet and physical activity. It is feasible and desirable to use
      ethnographic methods to discern the interactions of these factors that make each
      household unique. These results argue for dynamic intervention designs that
      operate from a broad contextual perspective.

PMID- 12192746
TI  - Recruitment and retention. A fistfull of dollars.

PMID- 12192745
TI  - Weight-related sports involvement in girls: who is at risk for disordered eating?
AB  - A 225-item questionnaire was completed by 5163 female 7th, 9th and 11th grade
      public school students in their classrooms to examine factors associated with
      eating disorders among girls involved in weight-related sports. Eating disorder
      symptoms were found in almost one third of girls involved in weight-related and
      non-weight-related sports. However, after controlling for grade, race, SES, and
      study design effect, girls in weight-related sports were 51% more likely to have
      eating disorder symptoms. Also, among girls in weight-related sports who had
      eating disorders, substance abuse, physical and sexual abuse history, depressive
      symptoms, suicide attempts, low family communication, and low parental caring
      were 98% to 377% more common.

PMID- 12192747
TI  - National service framework for children. No time for delay.

PMID- 12192748
TI  - Bringing it out into the open.

PMID- 12192749
TI  - Playing it safe.

PMID- 12192750
TI  - Where teachers fear to tread.

PMID- 12192751
TI  - The process of obtaining informed patient consent.
AB  - Obtaining patients' consent for procedures and operations is not simply a
      question of getting them to sign a form. It is a process that enables health
      professionals to explain to patients what is going to be done to them. It should
      inform them of the risks and benefits of any proposed procedures, and of any
      alternatives that might be available. It demonstrates respect for patient
      autonomy and should help to prevent legal action against health professionals.

PMID- 12192752
TI  - Nutritional care for adults in hospital.
AB  - Despite the fact that up to 40% of hospital patients may be malnourished, many
      nutritional referrals are inconsistent or inappropriate. Recent research has
      raised awareness of nutrition, but wide variations remain in the assessment and
      referral procedures used by hospital trusts. The final best practice statement in
      our series emerged from the responses of nursing and dietetic staff across
      Scotland. The statement focuses on five aspects of nutritional care: admission to
      hospital; nursing management of nutritional care; nutritional screening and
      documentation; criteria for nutritional referrals, and education and training.

PMID- 12192753
TI  - E-learning: a virtual challenge for educators.
AB  - This article examines e-learning in nurse education, specifically in learning
      disability nurse education, exploring its anticipated impact and discussing the
      importance of managing its implementation. Ways of utilising new technologies for
      the benefit of nursing students are analysed. The article also looks at how
      nurses' use of e-learning can help people with learning disabilities and cautions
      against relying on an overly technological approach in the humanistic fields of
      education and nursing.

PMID- 12192754
TI  - Telephone clinic improves quality of follow-up care for chronic bowel disease.
AB  - The unpredictable course of inflammatory bowel disease means that many patients
      are in remission when they are scheduled to attend a follow-up appointment. They
      often face long, unnecessary waits in congested outpatient departments when they
      require only verbal intervention. This article describes a year-long pilot study
      by a team of nurses and a consultant which involved offering telephone support to
      IBD patients. The service reduced unnecessary follow-up, provided rapid help
      during periods of relapse and promoted individualised care.

PMID- 12192755
TI  - Cardiopulmonary resuscitation. Advisory defibrillation--1.

PMID- 12192756
TI  - Day in the life.

PMID- 12192757
TI  - Nurses attack DoH for raising alarm over HIV.

PMID- 12192758
TI  - Using a customized surgical template for computer-guided implant surgery.
      Interview by Arun K. Garg.

PMID- 12192759
TI  - [Aesthetic eyebrow reconstruction by using follicular-unit hair grafting
      technique].
AB  - OBJECTIVE: To search a new option for aesthetic reconstruction of the eyebrow.
      METHODS: Under local anesthesia, a scalp strip was harvested from the back of the
      head, closed to the hairline. Under 2 times magnification, the strip was then
      divided into a series of follicular-unit micrografts with 1-3 hairs. Usually, 150
      micrografts were needed per eyebrow in a man whereas 100 micrografts in a woman.
      After the micro-slits or micro-slots were prepared in the recipient site, the
      grafts were implanted into the holes, parallel to the original hair directions.
      RESULTS: From Apr 1998 to Feb 2000, thirty-two patients with 48 eyebrow-losses,
      resulted from burn scar, skin grafting, chemical peeling, lesion excising or
      congenital loss, were treated by this one-session operation. All of the patients
      were satisfied with the results. The grafted hairs grow in the direction of
      normal eyebrow, which achieve 95%-96% survival even in a scarring area. The
      appearance of the reconstructed eyebrows was more natural, close to the normal
      eyebrow, compared to the traditional methods. CONCLUSION: The above-mentioned
      technique is a simple, safe and effective method for eyebrow reconstruction. It
      might be an ideal method for eyebrow reconstruction with the appearance much
      closer toa normal eyebrow.

PMID- 12192760
TI  - [A review of 204 consecutive free flap transfers for head and neck
      reconstruction].
AB  - OBJECTIVE: To review 204 consecutive free flap transfers for head and neck
      reconstruction in the new microsurgery unit. METHODS: Two hundred and four
      consecutive free flap transfers performed in 192 patients form May 1999 to March
      2001 were reviewed. The clinical data included the surgery date, defect
      description and site, stage and histology of the tumor, type of the flap used and
      complications. RESULTS: The free redial forearm flap was the most commonly used,
      followed by the free fibula flap, rectus abdominis flap, iliac crest flap, and
      latissimus dorsi flap. The overall success rate was 98.5%. The overall
      complication rate was 29.7%. The vessel thrombosis rate was 5.4%, and the flap
      salvage rate was 72.7%. CONCLUSION: Free tissue transfer in the head and neck
      region is safe and reliable. It is superior to the conventional pedicle flap
      technique.

PMID- 12192761
TI  - [Vascular endothelial growth factor (VEGF) accelerates maturation of
      prefabricated flap].
AB  - OBJECTIVE: To investigate the value of application of recombinant human VEGF to
      accelerate flap viability in a rat model of non-ischemic prefabricated flap.
      METHODS: Prefabricated Flaps were created in 48 SD rats. An autologous tail
      artery loop was anastomosed to the femoral artery and vein, and implanted
      subcutaneously in the lower abdomen. Flaps were divided into four groups of 12
      each. At the time of loop implantation, the control groups received 0.9% NaCl
      (Control 1) and 16% (V/W) polyvinyl alcohol (PVA) solution (Control 2). The
      treatment groups received VEGF in 0.9% NaCl (treatment 1) and VEGF in PVA
      (treatment 2). In each group, a 3 cm x 4 cm flap nurtured by the tail artery
      pedicle was elevated and resutured into place after 3, 4 and 5 weeks. The
      percentage of surviving skin of each flap was determined by planimetry 7 days
      after flap elevation. RESULTS: Mean skin survival areas at 3, 4, and 5 weeks were
      1%, 0%, 10% in control; 0%, 16%, 25% in control 2; 3.57%, 39.13%, 75.00% in
      treatment 1; 8.13%, 41.98%, 58.41% in treatment 2. VEGF significantly improved
      flap survival by 5 weeks (P < 0.05). CONCLUSION: These results suggest VEGF can
      accelerate maturation of prefabricated flaps.

PMID- 12192762
TI  - [Experimental study on microvascular architecture of human and rabbit flaps with
      two methods].
AB  - OBJECTIVE: To study effective method of showing the microvascular architecture of
      human and rabbit skin flaps. METHODS: According to endogenous alkaline
      phosphatase activity, Gomori-Takamatsu method and NBT/BCIP method were used to
      observe the microvascular architecture. RESULTS: Both methods had capability to
      demonstrate the microvascular architecture of the human skin flap, whereas the
      examining results of rabbits were negative. CONCLUSIONS: Great difference of
      endogeneous alkaline phosphatase activity exists in different animals. Gomori
      Takamatsu method and NBT/BCIP method are useful in study of microvascular
      architecture of human skin flaps.

PMID- 12192763
TI  - [Repair the infra-orbital defect with a rotation flap after basal cell carcinoma
      resection].
AB  - OBJECTIVE: To explore the method repairing the infra-orbital defect after basal
      cell carcinoma resection. METHOD: A facial rotation flap was applied to repair
      the infra-orbital defects from tumor resection in 28 cases. RESULT: All defects
      were repaired by this one-stage method, which avoided skin graft, shortened the
      operation time and minimized the operation trauma. The incision sears are
      inconspicuous. The facial contours are more satisfactory. CONCLUSION: This
      technique is simple and effective in repairing the infra-orbital defects, worthy
      of extensive application.

PMID- 12192765
TI  - [Experimental study on the toxic effects of hydrophilic polyacrylamide gel].
AB  - OBJECTIVE: To study the safety of Hydrophilic polyacrylamide gel (HPAG) through
      an animal experiment. METHODS: After HPAG was injected underneath the skin of SD
      rats, tissue specimens were taken for general and histological examinations. The
      cytotoxicity was evaluated by agar coverage and MTT method. RESULTS: It was
      determined that the cytotoxicity was over level-two. The toxicity to kidney was
      obvious. The local histological reaction was slight and a thin fibrous membrane
      was formed around HPAG, which became stiff gradually. The shape and location of
      the injected HPAG was not stable. The HPAG could not be drawn out completely.
      CONCLUSION: HPAG has obvious cytotoxicity and is not a suitable material as soft
      tissue implant for the bad shape and texture.

PMID- 12192764
TI  - [Design of axial flaps with color Doppler flow imaging technique].
AB  - OBJECTIVE: To study the effect of the color doppler flow imaging (CDFI) technique
      in the design of the axial pattern flap. METHODS: From March 1996 to June 1999,
      ten patients were included in this study. Among them, there were seven males and
      three females. Their defects ranged from 6 cm x 8 cm to 15 cm x 20 cm. Before
      operation, an axial flap was designed by the traditional method. Then CDFI
      technique of high frequency (5.0-7.5 MHz) was used to examine the major arterial
      supply of the flap and modify the design accordingly. At last, the modified flap
      was transferred to cover the defect. RESULTS: All the patients except one
      underwent the operation successfully. The cosmetic and functional results of the
      flap were excellent. CONCLUSION: CDFI is a simple, direct and accurate method for
      detecting the vascular supply of an axial pattern flap. This technique should be
      popularized to avoid blindness of flap design.

PMID- 12192766
TI  - [Clinical results of breast augmentation with polyacrylamide hydrogel injection].
AB  - OBJECTIVE: To investigate the complications in 16 patients who had breast
      augmentation with polyacrylamide hydrogel injection. The distribution and late
      changes of the injected material was observed. METHODS: The physical signs and
      symptoms of the 16 patients were classified. Ultrasound and infrared examinations
      or MRI were used in some cases. RESULTS: Two patients had operations for
      extraction. The injection material was distributed in the muscles diffusely, or
      existed in the breast and subcutaneous tissue as many masses. CONCLUSION: The
      reliability of this injection method for breast augmentation is in doubt.

PMID- 12192767
TI  - [Effects of conditioned medium derived from different keratinocytes on
      proliferation and collagen synthesis of hypertrophic scar fibroblasts].
AB  - OBJECTIVE: To observe the effects of supernatants of normal skin
      keratinocytes(NK) and scar keratinocytes(SK) on proliferation and collagen
      synthesis of hypertrophic scar fibroblasts(HSFB). METHODS: The supernatant,
      collected from cultured NK and SK, was added to the cultivated HSFB. The MTT
      method, 3H-proline incorporation and radioimmunoassay were employed to measure
      the cell proliferation, collagen synthesis and secretion. RESULTS: NK supernatant
      could inhibit HSFB proliferation and increase the collagen synthesis, but inhibit
      collagen secretion, as compared with the control group. On the contrary, SK
      supernatant could increase collagen synthesis and secretion, which had little
      effects on HSFB proliferation. CONCLUSION: Keratinocytes derived from normal skin
      and hypertrophic scar show different effects on hypertrophic scar fibroblasts.

PMID- 12192768
TI  - [The characters of proliferating activity and biosynthetic function of
      fibroblasts from abnormal scars after complete contact in vitro].
AB  - OBJECTIVE: This study was to determine the proliferating and biosynthetic
      characters of fibroblasts from abnormal scars and normal skins after complete
      contact in vitro. METHODS: 6 samples of keloid, hypertrophic scar and normal skin
      were collected respectively. Proliferation, inhibition and biosyntheses of
      different fibroblasts were investigated by detecting proliferating cell nuclear
      antigen(PCNA), P16, type I and III collagen proteins, and Pro alpha 1 (I) and Pro
      alpha 1 (III) procollagen gene expressions under the condition of fibroblast
      complete contact by means of cell culture, immunohistochemistry and molecular
      biological techniques, etc. RESULTS: Overlap and high levels of proliferating
      activity and biosyntheses of complete contact fibroblasts from keloids indicated
      that these fibroblasts lost the behavior of contact inhibition and density
      inhibition. However, proliferating activity and biosynthetic function of complete
      contact fibroblasts from normal skins reduced dramatically. Biosynthetic function
      of complete contact fibroblasts from hypertrophic scars was still very strong,
      but proliferating activity was lower than keloid and higher than normal skin.
      CONCLUSION: Proliferating and biosynthetic characters of complete contact
      fibroblasts from abnormal scars and normal skins were different, which may play
      an important role in the mechanisms of abnormal scar formation.

PMID- 12192769
TI  - [The experimental study on antisense TGF-beta 1 in inhibiting scar formation in
      III degree burn wound].
AB  - OBJECTIVE: To investigate the effect of antisense TGF-beta 1 in inhibiting scar
      formation during wound healing. METHODS: SD rats were divided into three groups
      after skin burn: group one was treated with antisense TGF-beta 1 oligonucleotide;
      group two was treated with antisense TGF-beta 1 recombinant plasmid and the
      control group. In different time, RT-PCR and immunohistochemistry were used to
      verify the expression of TGB beta 1 mRNA and protein. Type I Collagen mRNA
      expression was determined by hybridization in situ. Inflammatory reaction and
      collagen distribution were observed pathologically. RESULTS: In the groups
      received antisense ODN and recombinant plasmid, the expression of TGF-beta 1 mRNA
      and protein reduced during 14 days after burn. In the control group, type I
      collagen mRNA began to express at the second week and reached a peak at the
      fourth week, while the antisense groups kept low expression. The antisense group
      also showed mild inflammatory reaction and less synthesis of collagen.
      CONCLUSION: Antisense TGF-beta 1 could prevent the scar formation during wound
      healing.

PMID- 12192770
TI  - [Physical and psychological changes in patients with traumatic deformities during
      the treatment of tissue expansion].
AB  - OBJECTIVE: This study was to investigate the somatic symptoms and sychological
      specialties in trauma-deformed patients during tissue expansion. METHODS: Using
      our own questionnaires, fifty-seven patients were solicited to answer the
      questionnaires in three different treatment periods. RESULTS: It was found that
      local distension, pain and tickle were the common symptoms during expansion,
      while distension was most specific (P < 0.01). Pain and tickle also happened
      before implanting and after taking out of the expander. The patients often had
      high expectation toward tissue expansion. They felt nervous and anxious (P <
      0.01) during expansion. Their emotion and healthy self-evaluation changed
      obviously in different treatment periods (P < 0.01). CONCLUSION: Local distension
      is the most specific symptom during tissue expansion. Nervousness and anxiety are
      common in patients at that time. Their emotion change from depression to happy at
      first, and then from happy to slight depression.

PMID- 12192771
TI  - [Fat particle injection auto-transplantation a 10-year review].
AB  - OBJECTIVE: To summarize clinical experiences in fat particle injection auto
      transplantation during the past ten years. METHODS: Retrospective analysis of 334
      cases of fat particle injection auto-transplantation was done, and we suggested
      the correct method of liposuction and fat injection. RESULTS: In this series, one
      patient (0.29%) had a complication, thirty one patients (9.38%) had lower
      survival of autogenous fat-transplantation. CONCLUSION: In order to improve the
      results of fat-grafting, we must adopt the correct method of liposuction and
      follow the right rules.

PMID- 12192772
TI  - [The determination and significance of VEGF in the serum of hemangioma patients].
AB  - OBJECTIVE: Looking for an objective biomedical index to distinguish types and
      phases of hemangioma in order to provide an objective basis for selecting
      clinical treatment to hemangioma. METHODS: ELISA (enzyme-linked immunosorbent
      assay) was used to determine serum VEGF concentration of 15 patients with
      proliferative hemangioma, 6 with involuted hemangioma, 6 with vascular
      malformation and 8 infants of the control group. RESULTS: The serum VEGF
      concentrations of 15 proliferative hemangioma patients were significantly higher
      than those of involuted hemangioma patients, vascular malformation patients and
      control group infants. The serum VEGF concentrations of involuted hemangioma
      patients were a little bit higher than those of vascular malformation patients
      and control group infants, but without statistic significance. CONCLUSIONS: ELISA
      could easily and accurately determine the serum VEGF concentration of different
      types and different phases of hemangioma. The determination of serum VEGF
      concentration could provide guidance for selecting a protocol of systemic
      corticosteroid treatment for proliferative hemangioma. Combined with gene
      expression and distribution of VEGF and its receptors and some other cytokines,
      the determination of serum VEGF concentration could help elucidate the mechanism
      of proliferative hemangioma.

PMID- 12192773
TI  - Bringing cardiac healthcare directly to your hospital--and we do it with heart.

PMID- 12192774
TI  - Managing technological explosion in the medical management of coronary artery
      disease, Part II. DES economic modeling: budgeting strategies for drug-eluting
      stent technology.

PMID- 12192775
TI  - Troubleshooting your care plans. Improving the quality of nutrition care in LTC.

PMID- 12192776
TI  - You are up to bat! Third base: providing the needs of our patients.

PMID- 12192777
TI  - NCEP's new guidelines at a glance. National Cholesterol Education Program.

PMID- 12192778
TI  - [Geriatric nursing 2002 in Hannover: general practice, politics and prizes].

PMID- 12192779
TI  - ["Medicine and health" Capital City Congress: Nursing care can use opportunities-
      when policy cooperates].

PMID- 12192780
TI  - [Otorhinolaryngology--VII: Cotton swabs have no business in ears].

PMID- 12192781
TI  - [Hyposensitization to insect venom allergy: small animals--big effect].

PMID- 12192783
TI  - [Learning in nursing: ready and completed].

PMID- 12192782
TI  - [Nursing care of the ventilated child in the home environment--I: Maintaining
      chances for rehabilitation].

PMID- 12192784
TI  - [Explanation of different nursing care needs according to DRG: What nursing
      diagnoses can achieve].

PMID- 12192785
TI  - [Documentation of services in nursing: since you know what you do].

PMID- 12192786
TI  - [Nursing Care Dependency Scale: a measure of independence].

PMID- 12192787
TI  - [Nursing time and assessing personal needs with PLAISIR: answers to many
      questions].

PMID- 12192788
TI  - [A method for more patient orientation: consensus on multi-professional
      treatment].

PMID- 12192789
TI  - [Health care in Switzerland: society, cantons and communities work hand in hand].

PMID- 12192790
TI  - [Blind spots in nursing care responsibility toward the patients].

PMID- 12192791
TI  - [Multiple sclerosis--nursing specialty aspects within the scope of therapy
      management].

PMID- 12192792
TI  - [Zyprexa with superior effectiveness-risk relation. For every therapy situation a
      suitable dosage form].

PMID- 12192793
TI  - [Single parenting in Germany. Conflict between job and diapers].

PMID- 12192794
TI  - [Disinfection in housekeeping. More risk than benefit].

PMID- 12192796
TI  - [2 kinds of perception. Close up or at a distance?].

PMID- 12192795
TI  - [Medicine of greater immediacy. The one-sided model of "evidence based medicine].

PMID- 12192797
TI  - [What anesthetists fear. Reimbursement systems might brain pain therapy into
      question].

PMID- 12192798
TI  - [Quality of life and daily activities are significantly improved by transdermal
      fentanyl. Pain therapy in rheumatoid arthritis].

PMID- 12192799
TI  - [Pro and contra umbilical cord blood banking].

PMID- 12192800
TI  - [The dilemma in infection. Orientation between scientific definition and clinical
      status].

PMID- 12192801
TI  - [Life expectancy will increase to 100 years].

PMID- 12192802
TI  - [Inadequate care--prevention is vital--treatment is lengthy and costly. Decubitus
      ulcers can be prevented].

PMID- 12192803
TI  - [Status update of inpatient geriatric care].

PMID- 12192804
TI  - [Geriatric assessment of patients with dementia].

PMID- 12192805
TI  - [Foreign travel and medical problems].

PMID- 12192806
TI  - [Public health service and welfare nursing: problems hospitals and homes for the
      aged. Resistant pathogens caused to antibiotics].

PMID- 12192807
TI  - [The new biphasic analog insulin for a safe start in CT. NovoMix 30].

PMID- 12192808
TI  - [VACUTETTE sandwich tubes for blood coagulation tests].

PMID- 12192809
TI  - ["What is what". Multiple sclerosis].

PMID- 12192810
TI  - Adding up billing system offerings.

PMID- 12192811
TI  - Chemistry analyzers branching out.

PMID- 12192812
TI  - Implementing computerised patient records.

PMID- 12192813
TI  - Cutting the cord.

PMID- 12192814
TI  - A winning combination.

PMID- 12192815
TI  - Positive productivity: better billing.

PMID- 12192816
TI  - Workflow and patient-provider e-mail communications.

PMID- 12192817
TI  - Dueling platforms.

PMID- 12192818
TI  - What works. Power protection. Implementing the right power protection system
      eliminates critical seconds of down time during an outrage.

PMID- 12192819
TI  - What works. The UPS as network management tool.

PMID- 12192820
TI  - In support of decision support for IPAs.

PMID- 12192821
TI  - Wireless hotlist.

PMID- 12192823
TI  - Successful automation requires integrated effort. Involve physicians in selection
      of systems.

PMID- 12192822
TI  - Hospital uses scan form to integrate pathways and improve quality. Pathways focus
      on phases of care.

PMID- 12192824
TI  - Engaging physicians is key to successful CM. Use lessons from peer review.

PMID- 12192825
TI  - GA hospital uses scan forms for CVA clinical pathway.

PMID- 12192826
TI  - Proposed changes to EMTALA lack direction. Prior authorization, off-site
      locations addressed.

PMID- 12192827
TI  - Read between the lines for 'ominous' message. Challenge likely on EMTALA
      inpatient stance.

PMID- 12192828
TI  - Making decisions on breast cancer screening.

PMID- 12192829
TI  - Sorting out the manifestations of Lyme disease.

PMID- 12192830
TI  - Surgical options for coronary artery disease. A review for primary care
      clinicians.

PMID- 12192832
TI  - Mammography and evidence-based decision making.

PMID- 12192833
TI  - SC Colleagues in Caring update.

PMID- 12192834
TI  - School children and their health.

PMID- 12192835
TI  - Opportunities for practice in community/public health settings: a nursing
      education response to challenges in the 21st century.

PMID- 12192836
TI  - Preparing for nursing leadership in the 21st century: the doctor of Nursing
      Program at the University of South Carolina.

PMID- 12192837
TI  - Meeting the challenge of mobility in nursing education: one program's response.
AB  - Plans for the future include exploring linkages with baccalaureate programs,
      developing online offerings for courses at the ADN level, and tracking retention
      according to admission requirements. The department head has presented a proposal
      to the local BSN programs that will allow selected students in the ADN program to
      take one of their nursing courses at the RN-BSN level prior to graduation. A lead
      instructor at the ADN level is participating in a Title III grant to design
      online course offerings. A faculty member has been assigned the responsibility to
      track retention and develop a retention plan for the division. So far, we have
      recognized the following advantages of the new curriculum. 1) The liberal
      articulation for CNA and LPN means that these individuals can become registered
      nurses in less time. 2) Students have the opportunity to become credentialed at
      an earlier level and enter the workforce prior to becoming a registered nurse. 3)
      Implementation of the new curriculum has been a way to capitalize on college
      resources in order to maximize enrollment. In the past, some slots in the low
      enrollment NA and PN programs were not filled. As a result of the implementation
      of the new curriculum, we admitted a total of 65 (37%) more students in 2001 than
      we did in 2000 because we were able to fill available spaces in these low
      enrollment programs with ADN students. In a time of tight fiscal resources and
      increasing demands for healthcare providers, this multiple entry, multiple exit
      program provides an effective strategy for meeting the challenges confronting
      nursing education in the 21st century.

PMID- 12192841
TI  - Making progress on our pledge to 'inform the world about wound care'.

PMID- 12192840
TI  - Nursing informatics 101. What education qualifies an informatics nurse?

PMID- 12192843
TI  - Can the cuff position be varied when recording ABPI?

PMID- 12192842
TI  - Inflammation. 2: Its role in the healing of chronic wounds.
AB  - Why do some wounds fail to heal in the expected time? Part two of this article on
      inflammation discusses the possible causes, which include recurrence of trauma,
      bacterial and other contamination and perhaps, above all, the ageing process.

PMID- 12192844
TI  - The cellular proliferative phase of the wound repair process.
AB  - The proliferative--or new-tissue formation--phase of wound healing is complex.
      This article examines the changes that occur to cells during this stage and the
      effect on the extracellular matrix environment.

PMID- 12192845
TI  - Can wounds be left uncovered 48 hours after surgery?

PMID- 12192846
TI  - Compression bandaging: are practitioners achieving the ideal sub-bandage
      pressures?
AB  - Compression bandaging is the mainstay of conservative management of patients with
      venous ulceration. But debate is growing over what levels of pressure to apply
      and how to balance this with what patients can tolerate.

PMID- 12192847
TI  - Postoperative wound blistering: is there a link with dressing usage?
AB  - Practitioners on an orthopaedic ward used three different types of dressing on
      two groups of 100 patients who had undergone hip or knee operations, and compared
      the number of blisters that resulted. They describe their findings.

PMID- 12192848
TI  - Maceration of the skin and wound bed. 1: Its nature and causes.
AB  - Maceration, caused by prolonged exposure to moisture, can complicate the healing
      of wounds, especially chronic ones. This paper--the first of three reviewing the
      literature on its aetiology and management--looks at how maceration occurs.

PMID- 12192849
TI  - Space gain following the removal of first or second molars without orthodontic
      treatment--case reports.
AB  - First and second molar extraction, in combination with orthodontic treatment, is
      well represented in the literature. The following cases document situations in
      which first or second molars were removed without the introduction of orthodontic
      forces. The results show space gain and good eruption of the replacing second and
      third molars.

PMID- 12192850
TI  - Controlling the vertical dimension--the other dimension.

PMID- 12192851
TI  - TMJ fractures in children: importance of functional activation of muscles in
      preventing mandibular asymmetries and facial maldevelopment.
AB  - Normal development of the mandible as well as some portions of the upper jaw and
      face are related to good function of the masticatory apparatus: the integrity and
      interaction of bony and soft-tissue structures may be highly disturbed by injury
      of the TM joints and result in facial and occlusal disharmonies. When the
      neuromuscular system is in harmony, the mandibular muscles collectively exert
      their effect on both position and movement of the jaw and the loading of forces
      on the TM joints is optimal and balanced. Unfortunately, TMJ fractures may alter
      completely this balance with loss of the support to the mandible against the
      temporal component and loss of the functional effect of the lateral pterygoid
      muscle on the mandible. Disturbances in the harmonious interplay of the
      masticatory muscles may result in facial alteration and asymmetries. If not
      treated, the dysplastic patterns of growth continues and worsens during the
      years.

PMID- 12192852
TI  - MARA appliance.

PMID- 12192853
TI  - [Escherichia coli disulfide-forming related proteins: structures, functions and
      their application in gene engineering for expressing heterologous proteins in
      Escherichia coli].
AB  - The formation of disulfide bonds in secreted proteins of E. coli is a synergetic
      process depending on a series of Dsb proteins containing DsbA, DsbB, DsbC, DsbD,
      DsbE and DsbG. DsbA functions as an oxidant to form a disulfide bond between two 
      SH- in vivo and DsbB reactivates DsbA by reoxidizing it. Both DsbC and DsbG, two
      periplasmic proteins with isomerase activity, can correct mis-paired disulfide
      bonds introduced by DsbA although they recognize different substrates. DsbD, an
      inner membrane protein, plays a role in reducing DsbC and DsbG in vivo. It is
      regarded that DsbE has the similar function with DsbD. All DsbA, DsbC and DsbG
      have chaperone activity besides involving in the formation of disulfide bonds.
      Furthermore, their chaperone activity can promote the formation of protein
      disulfide bonds. There are a few reports dealing with soluble expression of
      heterologous proteins containing disulfide bonds assisted by DsbA and DsbC in E.
      coli. So far there has been no reports about the soluble expression of
      heterologous proteins promoted by DsbG. Our experiments first demonstrated that
      both DsbC and DsbG can improve the expression of single chain antibodies as
      soluble and functional forms in E. coli, and DsbG has additive effects with DsbC.

PMID- 12192854
TI  - [Development of the genetic transformation system in extremely halophilic
      archaea].
AB  - The development of the genetic transformation systems in extremely halophilic
      Archaea was reviewed in this paper. Included are the screening of selectable
      markers for resistance to antibiotics, the development of gene cloning and
      expression vectors, and the modifications of the host organisms.

PMID- 12192855
TI  - [Progresses in mouse chromosome engineering].
AB  - Mouse chromosome engineering, characterized by deletion and rearrangement of
      large fragment of chromosome, has been an important method for studying the
      function of mouse genome on a large scale. The latest progress in mouse
      chromosome engineering was introduced.

PMID- 12192856
TI  - [Gene and gene engineering of carotenoid biosynthesis].
AB  - Carotenoids have a range of diverse biological functions and actions, especially
      playing an important role in human health with provitamin A activity, anti-cancer
      activity, enhancing immune ability and so on. Human body can't synthesis
      carotenoids by itself and must absorb them from outside. However, carotenoid
      contents in many plant are very low, and many kinds of carotenoid are difficult
      to produce by chemical ways. With the elucidation of carotenoid biosynthetic
      pathway and cloning genes of relative enzymes from microorganisms and higher
      plants, it is possible to regulate carotenoid biosynthesis via genetic
      engineering. This article reviews gene cloning of carotenoid biosynthetic enzymes
      in microorganisms and higher plants, and advances in the studies of carotenoid
      production in heterologous microorganisms and crop plants using gene-manipulated
      carotenoid biosynthesis.

PMID- 12192857
TI  - [The development of peptide nucleic acid in gene regulation].
AB  - Peptide nucleic acid(PNA) is a kind of artificial DNA mimic. PNA hybridizes with
      DNA or RNA by means of Watson-Crick's base-pairs complementary with high
      stability, affinity and selectivity. PNA not only regulates. DNA replication, but
      also adjusts DNA transcription (or reverse transcription) and translation. Many
      applications have been explored as a new kind of molecular biological tool and a
      gene-targeting strategy.

PMID- 12192858
TI  - A transgenic mouse that targets the expression of Cre recombinase in pancreatic
      tissue.
AB  - The transgenic mice that express Cre recombinase in a tissue specific manner is a
      powerful tool in generating the conditional gene knockout mice. The rat insulin
      promoter was cloned target the expression of Cre in pancreatic tissue. The Cre
      gene was modified by adding the nuclear localization signal and the sequence for
      initiation by eukaryotic ribosomes at 5' terminal of the Cre gene. Cre gene was
      linked to the intron of human growth factor gene. This construct was introduced
      into the mouse eggs using microinjection. Seven mice were identified as founders
      carrying the Cre gene by PCR. The results of RT-PCR showed that the transgenic
      mouse from one founder could transcribe the foreign gene in pancreas. The
      Southern blot analysis indicated that the Cre recombinase expressed in pancreas
      of the transgenic mouse was functional.

PMID- 12192859
TI  - [Refolding and purification of the huGM-CSF(9-127)-IL-6(29-184) fusion protein].
AB  - The huGM-CSF(9-127)-IL-6(29-184) fusion protein was precipitated on column when
      being purified by Q Sepharose H.P. ion exchange chromatography after renaturation
      by dilution. To solve this problem, a novel purification and refolding strategy
      was adopted. Inclusion bodies was first purified by Q Sepharose H.P. ion exchange
      in 8 mol/L urea, followed by in situ refolding on column by Sephacryl S-200.
      Renatured fusion protein was obtained in a purity of more than 95%. It was showed
      that the method of refolding on gel filtration column is efficient, with relative
      refolding rate at 80%. By the whole procedure, refolding and purification of
      recombinant protein can be performed within one day. This strategy is also
      promising to be applied in large scale purification and refolding of recombinant
      protein from inclusion bodies in E. coli.

PMID- 12192860
TI  - [Production of SAM by recombinant Pichia pastoris].
AB  - To utilize Pichia pastoris to produce S-adenosyl-L-methionine (SAM), an
      intracellular expression vector harboring S. cerevisiae SAM2 was transformed into
      GS115. A recombinant strain having 2 copies of expression cassette was obtained
      through G418 resistance screening. This strain had higher SAM synthetase activity
      and higher SAM production capacity than the original strain, when cultured in
      medium containing methanol and methionine. The carbon source and nitrogen source
      of medium was optimized. The results showed SAM production by this strain was
      closely related to carbon metabolism. With supplementation of 0.2% glycerol every
      day from the beginning of 3rd day, this strain produced 1.58 g/L SAM when
      cultured in a medium containing 0.75% L-methionine and optimized carbon and
      nitrogen source after 6 days.

PMID- 12192862
TI  - [Overexpression and detection of the mutated glucose isomerase GIG138P and
      GIG138P-G247D in Streptomyces lividans].
AB  - The shuttle expression vectors pHZGI1 and pHZGI2 were successfully constructed by
      inserting structural genes of GI containing single mutated site G138P and double
      mutated site G138P-G247D into E. coli-Streptomyces shuttle vector pHZ-1272,
      respectively. Then they were transformed into S. lividans TK54 strain by
      protoplast transformation. SDS-PAGE indicated that two shuttle vectors in TK54
      strain expressed obviously specific bands at 42.5 kD after inducted by 2
      micrograms/mL thiostrepton. Optical densitometric scan showed that the content of
      the mutant enzymes GIG138P and GIG138P-G247D were about 19% and 22% of dissoluble
      proteins, respectively. Western blotting farther proved that GIG138P and GIG138P
      G247D were expressed in S. lividans TK54.

PMID- 12192861
TI  - [The expression of Aeromonas hydrophila ompTS gene and the immunogenicity of
      recombinant OmpTS].
AB  - Primers were designed based on ompTS gene reported recently. With the specific
      primers, one target fragment about 1024 bp lacking the signal sequence of ompTS
      gene was amplified from A. hydrophila genomic DNA via PCR. The ompTS gene was
      hyperexpressed using gene fusion expression vector pRSET system, and the
      recombinant OMP exhibited a size of 39.9 kD with SDS-PAGE and Western blot
      analysis, which showed about 51% of total lysate proteins. Antibody to the
      purified recombinant OMP reacted not only to the recombinant OMP but also to the
      purified OMPs from A. hydrophila in ELISA and the 36.9 kD OMP in Western blot.
      The result indicates that the recombinant OMP has the same epitope with the
      nature one.

PMID- 12192863
TI  - [Construction of eukaryotic expression vector using neomycin-resistance gene
      mutant as selectable marker].
AB  - Neomycin-resistance gene is widely used as a selectable marker in eukaryotic
      expression vector. It codes neomycin phosphotransferase II (NPT II) which confers
      resistance to various aminoglycoside antibiotic such as G418 and kanamycine. In
      this work, by site-directed mutagenesis the neo gene mutant was obtained. The
      expression vector pmDNA using the neo gene mutant as selectable marker has been
      constructed. After inserting interest luciferase gene, the expression plasmid
      pmDNAluc + was stably transfected CHO-K1 cells. As a result, the expression
      positive ratio reaches to approximate 95% and the ratio of high expression
      colonies is apparently higher than the controls.

PMID- 12192864
TI  - [Screening for resistance gene candidate from a genomic TAC library of Triticum
      aestivum-Haynaldia villosa translocation line 6VS/6AL by pooled PCR].
AB  - A pair of degenerate primers were designed based on NBS (nucleotide binding site,
      NBS) domain of resistance(R) gene and used to perform PCR with cDNA from the
      translocation line 6VS/6AL of Triticum aestivum-Haynaldia villosa. A clone (N7)
      characterized with NBS was obtained by sequencing analysis. Two specific primers
      were designed from the N7 sequence and used to screen a genomic TAC
      (transformation-competent artificial chromosome, TAC) library of 6VS/6AL
      consisting of ca. 2 x 10(6) clones. The library was stored as clone pools in
      twenty-two 96-well plates, each well containing approximately 1000 TAC clones.
      TAC plasmids were prepared from all the 2112 pools. Using a pooled PCR screening
      procedure, a positive TAC clone having a 40 kb insert was obtained. The positive
      clone was confirmed by Southern hybridization with the NBS fragment as a probe.
      The results indicate that the pooled PCR method is effective for screening of
      genomic libraries having large number of clones.

PMID- 12192865
TI  - [Study on optimization of expression, purification, properties and biological
      function of recombinant human sBLyS].
AB  - The prokaryotic expression plasmid pET-30a(+)/sBLyS was constructed and
      transformed into E. coli BL21 (lambda DE3). The recombinant protein was found to
      be highly expressed by the plight of soluble part and inclusion body. For the
      sake of enhancing the proportion of the soluble part, inducement at 16 degrees C
      for 12 h was ascertained. The expressing product was then purified by Ni2+
      affinity chromatography gel. PI of the recombinant human sBLyS(rhsBLyS) is about
      7.1-7.3 and it assembles into a homotrimer. The effect of rhsBLyS on B
      lymphocytes by MTT method told us the B lymphocytes' proliferating capacity dose
      depended on concentration and also stimulating time of the rhsBLys. With
      rhsBLyS(2 micrograms/mL) stimulating 3 days, B lymphocytes can proliferate the
      most.

PMID- 12192866
TI  - [Callus induction and regeneration from mature seeds of indica rice minghui 63
      and anti-fungal assay of transgenic rice plants].
AB  - A large number of callus from mature seeds of indica rice minghui 63 were
      obtained through pre-induction on medium with 2 mg/L 2,4-D but without inorganic
      and organic components for 9 days. Trichosanthin gene was transferred into indica
      rice minghui 63 by using agrobacterium with the help of bombardment and the
      transgenic plants were obtained by inducing regeneration. Southern and Western
      blot analysis showed that the trichosanthin gene had been transferred into genome
      of minghui 63 and expressed in rice plants. The anti-fungal assay suggested that
      transgenic rice plants enhanced resistance to infection of Pyricularia oryzae.

PMID- 12192867
TI  - [Construction and in vitro activity of specific dual-ribozyme against alpha 1 (I)
      and (III) procollagen genes].
AB  - Overexpression of procollagen gene can cause the extraordinary increase of
      collagen's synthesis and therefore lead to the keloid and hypertrophic scar. To
      utilize ribozyme to suppress the expression of procollagen genes, a eukaryotic
      expression recombinant plasmid containing a dual-ribozyme gene against alpha 1
      (I) and alpha 1 (III) procollagen genes was constructed. The ribozyme from in
      vitro transcription was incubated with target transcripts from recombinant
      plasmids which separately contained the fragments of the second exons of pro
      alpha 1 (I) and pro alpha 1 (III) collagen genes under various experimental
      conditions. The results showed that the dual-ribozyme could efficiently catalyze
      the specific cleavage of the target RNAs at 37 degrees C, 42 degrees C, 50
      degrees C and Mg2+ concentration from 10 mmol/L to 20 mmol/L. This work provided
      a basis for further study on the ribozyme to suppress the expression of
      procollagen genes and control the cicatrization.

PMID- 12192868
TI  - [Study on construct and expression of synthetic genes encoding spider dragline
      silk in Escherichia coli].
AB  - Dragline spider silk produced from Nephilia clavipes major ampullate is a natural
      fibrous protein with specific mechanical properties such as high tensile strength
      and elasticity. Synthetic gene monomer encoding recombinant spider silk protein,
      based on the known repetitive protein sequence and partial cDNA sequence of
      dragline silk, was constructed and expressed. DNA monomer sequences were
      multimerized to encode high molecular weight synthetic spider silks using a "head
      to-tail" construction strategy. Multimer was cloned into pET30a(+), a prokaryotic
      high potency expression vector, and induced with IPTG. The protein from 8-unit
      repeat was produced in Escherichia coli at levels up to 20 mg/L. The protein was
      easily purified with high recovery by using an metal ion affinity chromatography
      and purity was over 90%. The results of SDS-PAGE and Western blot suggested that
      the mass of the expression product was about 37 kD. This value and amino acid
      analysis were consistent with those of theoretic calculation.

PMID- 12192869
TI  - [A novel resolution vector with Bacillus thuringiensis plasmid replicon ori44].
AB  - The resolution recognization sites of transposon Tn4430 of Bacillus thuringiensis
      was inserted into cloning vector pRSET B and pUC19, resulting recombinant
      plasmids pBMB1201 and pBMB1202. Both of the mini res fragments, BamHI/HindIII
      fragment in pBMB1201 and EcoRI/HindIII fragment in pBMB1202, were ligated to the
      3.3 kb EcoRI/HindIII fragment of shuttle vector pHT3101, which contained the ori.
      Ec, ampr and emr antibiotic resistant genes, resulting recombinant plasmid
      pBMB1203. After deleted the BamHI and EcoRI sites which located ouside the two
      res sites, resolution vector pBMB1204 was resulted. There are multiple cloning
      sites between two copies of resolution sites which have the same direction. The
      plasmid replication origin ori44, which come from B. thuringiensis sub sp.
      kurstaki strain YBT-1520, was inserted into the multiple cloning sites of
      pBMB1204 and then resolution shuttle vector pBMB1205 was obtained. With
      spectinomycin resistant gene as target, it was found that the resolution rate is
      100% and the stability of the resolved plasmid is 93%. Using this shuttle vector,
      antibiotic resistance markers and other non-B. thuringiensis DNA can be
      selectively eliminated after the selection of transformants by antibiotic
      resistance marker. This vector is very useful to solve the gene safety problem
      while has no effect on target gene expression.

PMID- 12192870
TI  - [Site-directed mutation of PoIFN-alpha and its expression in Escherichia coli].
AB  - By using huge primer PCR Cys86 (TGC) of PoIFN-alpha was mutated to Tyr(TAC), and
      the first code TGT was simultaneously changed to TGC, which is a bias code of E.
      coli. The expression plasmid pGEX-IFN was constructed successfully. Recombinant
      porcine IFN alpha, which is expressed as inclusion bodies, was about 20% of the
      total proteins. The inclusion body was dissolved in 8 mol/L urea and subsequently
      renatured by dilution in refolding buffer. In order to obtain pure protein, the
      renatured IFN alpha was purified by FPLC, and the cytokine activity (5200 IU/mg)
      was verified by inhibiting the cytopathic effect.

PMID- 12192871
TI  - [In vitro culture of umbilical cord blood MNC and CD34+ selected cells].
AB  - For in vitro studies, both CD34+ selected cell and mononuclear cell (MNC) can be
      used to expand hematopoietic stem/progenitor cells. To investigate the expansion
      characteristics of mononuclear cells (MNC) and CD34+ selected cells the two cell
      fractions were cultured in the medium containing cytokine cocktails of SCF + IL-3
      + IL-6 + FL + Tpo. It was found that the CD34+ selected cells had presented a
      high proliferation potential. The expansion of CD34+ selected cells could be
      maintained for 8 weeks while that of MNCs declined after 4 weeks. During the
      culture period, the maximum expansion of total cells in CD34+ selected cell
      culture achieved 31,270.9 +/- 8640.5 times, while that of MNC reached 50.9 +/-
      8.2 times only. In the culture of MNCs, the colony density and the proportion of
      CD34+ cells increased from day 0 to day 7. However, in the culture of CD34+
      selected cells, both the colony density and the proportion of CD34+ cells
      declined continuously during the whole culture period. During the ex vivo culture
      of CD34+ selected cells, the maximum expansion of CFU-GM and CD34+ cells achieved
      185.7 +/- 14.1 fold and 191.7 +/- 188.8 fold, respectively. They are much higher
      than that of MNC, which were 12.4 +/- 3.2 fold and 50.6 +/- 33.2 fold only. While
      the BFU-E of both cell fractions only expanded by few times, which were 7.2 +/-
      5.2 and 10.1 +/- 3.4 times, respectively. The results showed that the CD34+
      selected cells culture could obtain more CFU-GM cells and CD34+ cells during the
      whole culture period.

PMID- 12192872
TI  - [Effects of different methanol feeding strategy on hirudin production in high
      density fermentation by recombinant Pichia pastoris].
AB  - Four different methanol feeding modes were evaluated in the hirudin production in
      high-density fermentation by Pichia pastoris. It was difficult to avoid methanol
      excessive in the broth with the feeding strategy only based on DO level. On the
      other hand, the fluctuation in methanol concentration was observed with methanol
      feeding strategy by off-line gas chromatography. However, the stable methanol
      concentration was perfectly achieved by the on-line monitoring with methanol
      sensor. The supply of energy was improved by feeding glycerol at a limited rate
      as well as methanol in the induction phase. Therefore, the high cell dry weight
      (162 g/L) and high hirudin activity (2.4 x 10(4) ATU/mL or 1.7 g/L) was obtained
      in the fed-batch fermentation of recombinant Pichia pastoris by methanol-glycerol
      mixed feeding.

PMID- 12192873
TI  - [Cloning and expression of the cecropin B-thanatin hybrid antimicrobial peptide
      in Escherichia coli].
AB  - A 44-residue hybrid peptide (CB (1-24)-Arg-Ser-Tyr-Tan (4-21)) incorporating 1-24
      residues of cecropin B (CB) and 4-21 residues of thanatin (Tan) was designed and
      constructed. The CB-Tan gene was cloned into expression plasmid pGEX-3X and
      expressed in E. coli BL21. The fusion protein was purified by affinity
      chromatography. After digested with enterokinase the gene product released with
      antibacterial activity and gave one band in Tricine-SDS-PAGE.

PMID- 12192874
TI  - [Single-chain urokinase-type plasminogen activator (scu-PA) purification by
      immuno-affinity chromatography].
AB  - The only difference of primary structure between single-chain prourokinase (pro
      UK or scu-PA) and two-chain urokinase (UK or tcu-PA) is the cleavage of a single
      peptide bond (Lys158-Ile159) and transform scu-PA into its active two-chain form.
      A 13-peptide (Thr-Leu-Arg-Pro-Arg-Phe-Lys-Ile-Ile-Gly-Gly-Glu-Cys), which spans
      the cleavage peptide bond, was synthesized and linked to KLH (Keyhole limpet
      hemocyanin). The Balb/c mice were immunized by the conjugated protein with proper
      adjuvant. According to the Kohler and Milstein's methods, a hybridoma cell line
      G7 secreting monoclonal antibody specific for scu-PA was obtained. The anti-scu
      PA McAb, purified from the supernatant of porous microcarrier hybridoma cell
      culture, was conjugated to CNBr-activated Sepharose 4B to prepare an immuno
      affinity chromatography column. The u-PA was purified only by this affinity
      column from the supernatant of cultivating the u-PA-producing recombinant CHO
      cell, the u-PA recovery ratio is 90.4%, the purification factor was about 50,
      with the specific activity of 1.2 x 10(5) IU/mg, the scu-PA ratio in the u-PA
      product was 96.3%. Compared to immuno-affinity chromatography, the 3-step process
      for purifying u-PA (cation-exchange column, gel filtration column and benzamidine
      affinity column) has a u-PA recovery ratio of about 65%, with a specific activity
      of 1.0 x 10(5) IU/mg, and an scu-PA ratio of about 90%. These results showed that
      immuno-affinity chromatography is simple to recover u-PA and effective to
      separate scu-PA from tcu-PA.

PMID- 12192875
TI  - [Continuous perfusion culture hybridoma cells for production of monoclonal
      antibody].
AB  - Hybridoma cells were cultured by continuous perfusion in Fibra-Cel of 5L packed
      bed bioreactor for 22 days in low serum or serum-free media. The corresponded
      amino acids were fed and serum concentration was decreased by analyzing glucose
      concentration, oxygen uptake rate, secretary antibody amount and amino acids
      concentration in culture supernatant. Comparing with continuous perfusion culture
      that amino acids were not fed, antibody amount of production was increased about
      2-3 times. The inoculated cell density was 2.5 x 10(5) cells/mL, while the final
      cell density was 8.79 x 10(8) cells/mL. Antibody production was reached 295
      mg/L/d at average level, and the highest level was reached 532 mg/L/d. These
      results provided a primary mode of enlarge culture for monoclonal antibody
      industralization.

PMID- 12192876
TI  - [Cloning and expression of canine interferon-gamma gene in mouse SP2/0 cell
      line].
AB  - Canine Interferon-gamma (CaIFN-gamma) cDNA was cloned from spleen T cells of dog
      by reverse transcription-polymerase chain reaction (RT-PCR). CaIFN-gamma cDNA
      were digested with Hind III and Not I, and inserted into pRc/CMV2 expression
      vector. The pRc/CMV2/CaIFN-gamma vector was sequenced, and predicted to produce a
      signal peptide of 23 amino acids and a mature protein of 143 amino acids with a
      molecular weight of 19 kD. Two potential N-glycosylation sites are located at
      positions 16 and 83 of the mature protein. Comparison of the CaIFN-gamma protein
      sequence with that of CaIFN-gamma reported from DDBJ/GenBank revealed a homology
      of 99%. To establish a long time expression system, pRc/CMV2/CaIFN-gamma vector
      was transfected into mouse SP2/0 cell line. The SP2/0 cells culture supernatants
      was harvested and the antiviral activity was measured following cytopathic-effect
      inhibition assay using Madin-Darby Canine Kidney (MDCK)-vesicular stomatitis
      virus(VSV) system. Initial transformants with G418 phenotype produced recombinant
      CaIFN-gamma titers ranging from 2,500 to 5,000 u/mL of culture medium.

PMID- 12192877
TI  - [Effect of microbial elicitors on sclerotia biomass and carotenoid yield in
      surface cultures of Penicillium sp.PT95].
AB  - Six kinds of elicitors were prepared respectively from Neurospora crassa,
      Monascus purpureus, Sporobolomyces roseus, Rhodotorula rubra, Nocardia sp. N89
      and Actinoplanes sp. A05. When Penicillium sp. PT95 was incubated in Czapek's
      agar plates containing appropriate amounts of elicitors, both its sclerotia
      biomass and carotenoid content accumulated in sclerotia were enhanced
      significantly (P < 0.01). Among tested elicitors, the elicitors from the fungi N.
      crassa, M. purpureus, S.-roseus and R. rubra were more effective than those from
      the actinomycetes Nocardia sp. N89 and Actinoplanes sp. A05; the elicitor from M.
      purpureus gave the highest carotenoid yield of 599 micrograms/plate, 2.76 times
      higher than that of control. Every one of elicitors except that from M. purpureus
      could increase significantly the proportion of beta-carotene in total carotenoids
      (P < 0.01).

PMID- 12192878
TI  - [Optimization of cultivation conditions in se-enriched Spirulina platensis].
AB  - Orthogonal combination design was adopted in examining the Spirulina platensis
      (S. platensis) yield and the influence of four factors (Se content, Se-adding
      method, S content and NaHCO3 content) on algae growth. The results showed that Se
      content, Se-adding method and NaHCO3 content were key factors in cultivation
      conditions of Se-enriched S. platensis with the optimal combination being Se at
      300 mg/L, Se-adding amount equally divided into three times and NaHCO3 at 16.8
      g/L. Algae yield had a remarkable correlation with OD560 and floating rate by
      linear regression analysis. There was a corresponding relationship between
      effects of the four factors on algae yield and on OD560, floating rate too. In
      conclusion, OD560 and floating rate could be served as yield-forming factors.

PMID- 12192879
TI  - [Technological advances of serial analysis of gene expression].
AB  - Serial analysis of gene expression (SAGE) is an effective method of determining
      gene expression profiles of tissues and organs under different conditions. In
      this paper, the detail protocol of SAGE was introduced and some modified
      procedure of SAGE was reviewed.

PMID- 12192880
TI  - [Studies on improving crop nutritional quality through gene engineering].
AB  - This paper summarizes the studies on improving crop nutritional quality including
      protein, saccharide and lipid through gene engineering in recent 10 years.
      Special emphasis is laid upon the improvement of protein contains and amino acid
      components. The food safety caused probably by gene engineering and some ways to
      solve the problem are introduced briefly.

PMID- 12192881
TI  - The case of female genital mutilation.

PMID- 12192882
TI  - Peripheral arterial disease: drug therapy.

PMID- 12192883
TI  - Safety and efficacy of topical nitroglycerin for treatment of vulvar pain in
      women with vulvodynia: a pilot study.
AB  - OBJECTIVE: To evaluate the safety and efficacy of topical nitroglycerin cream for
      the treatment of vulvar pain in women with vulvodynia. METHODS: A total of 34
      women diagnosed with vulvodynia were included in this study. Patients were
      treated with 0.2% nitroglycerin cream in the clinic. The cream was applied
      directly to the skin at the genital/vulvar area where the pain was located.
      Patients who did not experience any adverse side effects were instructed to use
      the cream at home at least three times per week, 5-10 minutes prior to sexual
      relations. Patients completed a pretreatment pain scale at baseline and a
      posttreatment pain scale questionnaire 4-6 weeks later. RESULTS: Twenty-one
      patients completed both the pre- and posttreatment pain scale questionnaires, and
      13 patients completed only the posttreatment pain questionnaire. Thirty-one
      patients (91.5%) stated that "overall" their pain had improved. Analysis of the
      pre- and posttreatment questionnaires revealed a significant decrease in pain
      intensity on a scale of 0 (no pain) to 5 (excruciating pain; 3.95-2.57; P <
      .000). There was also a significant decrease in the frequency of overall painful
      episodes on a scale of 0 (never) to 4 (always; 3.25-2.15, P < .006). All 21
      patients reported "improvement" of pain during sexual activity (3.65-2.15; P <
      .005). CONCLUSION: Topical nitroglycerin is safe and effective in providing
      temporary relief of introital dyspareunia and vulvar pain in women with
      vulvodynia. Women who completed this study experienced significant improvement in
      their overall pain and pain with sexual activity after nitroglycerin use. A
      larger placebo-controlled study is necessary to establish the optimum dosage
      level and to minimize the side effects.

PMID- 12192884
TI  - Hormones, pregnancy, and rheumatoid arthritis.
AB  - Rheumatoid arthritis (RA) is a chronic autoimmune disorder that, like most
      autoimmune diseases, is more common in women than in men. A significant body of
      evidence implicates gender-specific factors in facilitating the development of
      RA. Pregnancy has an ameliorating effect on disease activity, while the disease
      tends to flare in the postpartum period. Estrogen-containing oral contraceptives
      can modify the disease course or onset, hinting at a role for this hormone in
      disease pathogenesis. Breast-feeding appears to increase the risk of RA, possibly
      through the actions of the lactation hormone prolactin. Nonhormonal factors
      associated with pregnancy may also be important in women with RA, especially the
      degree of maternal-fetal human leukocyte antigen (HLA) incompatibility. This
      article reviews data from human clinical and epidemiologic investigations as well
      as experimental findings in animal models of chronic arthritis. Possible
      mechanisms by which gender-specific factors modulate immune function are also
      discussed.

PMID- 12192885
TI  - Incidence and management of arrhythmias in women.
AB  - There are gender-specific differences in the nature and frequency of specific
      cardiac arrhythmias. Sex-specific variations in the electrophysiologic structure
      of the heart and/or hormonal effects on modulating ionic channel function may
      help to explain some of these differences, such as the increased prevalence of
      symptoms of congenital long QT syndrome in women, and the increase in episodes of
      supraventricular tachycardia in the perimenstrual period in susceptible patients.
      On the other hand, women suffer only 20% of sudden cardiac deaths. Fewer women
      than men have been enrolled in clinical trials for the treatment of ventricular
      arrhythmias because of difficulty in recruiting female patients, exclusion of
      women due to comorbid conditions, and/or the later appearance of coronary artery
      disease in females compared to males. Management of arrhythmias in women is often
      different from that in men, as women are less likely to receive a dual-chamber
      pacemaker and to have automatic defibrillator implantation, even when clinically
      appropriate. These differences may be due to the smaller size of women, a
      difference in the frequency of comorbid conditions, and patient preference, with
      women more likely to decline aggressive therapy. This article discusses the
      differences in presentation and the frequency of specific arrhythmias in women,
      and suggests measures to improve arrhythmia management in the female patient.

PMID- 12192886
TI  - Gender discrepancy in cataract surgery.

PMID- 12192887
TI  - Rethinking circumcision: medical intervention, religious ceremony, or genital
      mutilation?

PMID- 12192888
TI  - Effect of an oxytocin antagonist on plasma oxytocin levels during nocturnal
      uterine contractions in the pregnant baboon.
AB  - TT-235 is a potent oxytocin (OT) antagonist that blocks the action of OT at the
      receptor level. Previous studies have shown that pregnant baboons demonstrate
      nocturnal uterine contractions induced by OT as they near delivery. The purpose
      of this study was to evaluate the changes in plasma OT levels following uterine
      contraction blockage with TT-235. A tethered pregnant baboon model in its last
      trimester of pregnancy was used. Three blocks of arterial blood samples,
      immediately before, plus 1 h and plus 2 h following an OT antagonist injection,
      were collected once nocturnal uterine contractions were detected. Each block
      consisted of a continuous 10 min withdrawal with 10 samples per block (1 ml/min).
      A TT-235 dosage of 300 micrograms/kg and saline for control were utilized.
      Uterine activities were monitored as pressure changes in the amniotic fluid, and
      the frequency and mean amplitude of contractile activity per 10 min intervals
      were expressed as contractile force. Plasma OCT levels were determined by a
      radioimmunoassay following plasma extraction with petroleum ether. The
      contractile force was decreased by 77% (p < 0.05) within 2 h after TT-235
      administration while it increased 23% following saline infusion. Plasma OT levels
      were unchanged following saline infusion while they increased 82% (p < 0.05) 2 h
      after the administration of TT-235. If a positive feedback existed between
      uterine contractions and OT release, one would expect plasma OT levels to be
      decreased with contractile activity following TT-235 infusion. Since this is not
      the case in the present study, the data suggest that there is either a negative
      feedback or an independent relationship between nocturnal uterine contractions
      and OT release.

PMID- 12192889
TI  - Human chorionic gonadotropin exhibits normal biological activity in patients with
      recurrent pregnancy loss.
AB  - To test the hypothesis that the structural abnormality of human chorionic
      gonadotropin (hCG) may induce recurrent pregnancy loss, we examined the
      biological activity of hCG in pregnant women with a history of repeated
      miscarriages (n = 44). Pregnant women without a history of miscarriage (n = 85)
      were included as controls. Serum hCG, estradiol (E2) and progesterone levels were
      found to be significantly lower in the pregnancy loss group. There was no
      difference in serum thyroid hormone levels. Sera from both groups of women were
      then incubated with Chinese hamster ovary (CHO) cells transfected with
      hCG/luteinizing hormone receptor (CHO-hCG/LHr) or human thyroid stimulating
      hormone receptor (CHO-hTSHr). Biological response to hCG in women with recurrent
      pregnancy loss was identical to that of women in the control group in both CHO
      hCG/LHr and CHO-hTSHr cells. When sera were subjected to high performance liquid
      chromatography, no difference in hydrophobicity was observed between control and
      patients groups. The structure of the hCG molecule and its biological activity in
      women with a history of recurrent pregnancy loss are apparently not different
      from those in women with normal pregnancy. Lower serum progesterone and E2 levels
      in the patient group can be explained by lower serum hCG levels in these women.
      Intrinsic gonadotropic and thyrotropic activities of the hCG molecule appear to
      play no major role in recurrent pregnancy loss.

PMID- 12192890
TI  - Maternal nitric oxide supplementation increases adrenomedullin concentrations in
      growth retarded fetuses.
AB  - Nitric oxide (NO) and adrenomedullin (AM) are both involved in the regulation of
      fetoplacental circulation in human pregnancy. The aim of this study was to
      investigate the effect of maternal NO supplementation in pregnancies complicated
      by intrauterine growth retardation (IUGR) on maternal and fetal NO and AM
      concentrations and their correlation with uteroplacental and fetal blood flow. We
      studied 20 pregnant women with IUGR and impaired uteroplacental blood flow
      between 27 and 35 weeks of gestation randomly selected to receive either
      transdermal glyceryl trinitrate or placebo. Maternal NO metabolites (NOx) and AM
      concentrations did not change before and after NO treatment. AM levels were
      significantly higher in growth retarded fetuses whose mothers received NO donors
      (114.1 +/- 17.6 pg/ml) than in untreated fetuses (59.8 +/- 38.6 pg/ml), whereas
      NO treatment did not affect significantly fetal NOx levels. Fetal AM correlated
      with middle cerebral artery pulsatility index in untreated IUGR but not in NO
      treated pregnancies.

PMID- 12192891
TI  - Effects of pregnancy on insulin receptor in liver, skeletal muscle and adipose
      tissue of rats.
AB  - The mechanism responsible for insulin resistance during pregnancy remains
      unclear. Considerable evidence indicates that the insulin receptor plays an
      important role in insulin sensitivity. It seems possible that the hormonal milieu
      during gestation could have an effect on the insulin receptor. In the present
      study, measurements of tyrosine phosphorylation and protein content of the
      insulin receptor and expression of its gene in liver, skeletal muscle and adipose
      tissue indicate that during pregnancy significant changes occur in these
      parameters. We found that at the end of early gestation (day 10), muscle and
      adipose tissue are very sensitive to insulin action because the amount,
      phosphorylation and gene expression of insulin receptor is higher than in late
      gestation (days 15-20), while the tissue which is most sensitive to insulin
      action in late gestation is the liver. Our hypothesis is that these results are
      connected with changes in the concentrations of estradiol and progesterone
      observed during pregnancy. In conclusion, our previous and present findings seem
      to demonstrate that the different concentrations of gestational hormones play an
      important role in insulin sensitivity in this period and that each tissue
      responds in the most appropriate manner to guarantee the gestation in its
      entirety.

PMID- 12192892
TI  - Thyroid carcinoma on an ovarian teratoma: a case report and review of the
      literature.

PMID- 12192893
TI  - Ovarian steroid cell tumor and a contralateral ovarian thecoma in a
      postmenopausal woman with severe hyperandrogenism.
AB  - A 49-year-old woman presented with rapidly progressing hirsutism, receding
      hairline, male-pattern baldness and deepening of voice, which had developed over
      the past 2 years. Hormonal evaluation showed a markedly elevated serum
      testosterone level (418 ng/dl) and no evidence of increased production of
      cortisol, dehydroepiandrosterone, dehydroepiadrosterone-sulfate, androstenedione,
      or 17-hydroxyprogesterone. Transvaginal ultrasound examination suggested the
      presence of a small mass within the left ovary, but all other radiological
      studies, including adrenal and ovarian computed tomography, magnetic resonance
      imaging, radio-labelled cholesterol scintigraphy and positron emission
      tomography, were negative. Subsequently, bilateral selective venous sampling
      showed a marked testosterone gradient in the right ovarian vein. Bilateral
      salpingo-oophorectomy was performed (the patient had had a previous vaginal
      hysterectomy), and histopathological examination revealed a 10-mm steroid cell
      tumor within the right ovary and a 15-mm thecal cell tumor within the left ovary.
      The postoperative serum testosterone level returned to normal and the patient
      showed a slow regression of clinical symptoms. The simultaneous occurrence of a
      virilizing ovarian steroid cell tumor and an apparently non-functioning thecoma
      within the contralateral ovary emphasizes the potential pitfalls that may exist
      in the preoperative evaluation of patients with markedly increased testosterone
      production.

PMID- 12192895
TI  - Gender differences in contractile and relaxing responses of aortic rings from
      lipopolysaccharide-treated rats.
AB  - Aortic rings from male and female Sprague-Dawley rats were placed in organ
      chambers filled with Krebs solution, and the isometric tension was recorded.
      There were no gender differences in responses to potassium chloride or
      phenylephrine in either intact or endothelium-denuded rings from control animals.
      Treatment with 10 mg/kg of lipopolysaccharide (LPS) attenuated the contractile
      response to potassium chloride in intact, but not in endothelium-denuded rings,
      and suppressed the phenylephrine contractions in rings both with and without
      endothelium from male and female rats. Endothelium-dependent and--independent
      relaxation by acetylcholine and the nitric oxide donor diethylamine/NO,
      respectively, did not depend on gender and were equally suppressed by LPS
      treatment. Treatment with LPS accentuated the effects of oxyhemoglobin in rings
      with and without endothelium and this was significantly larger in rings from
      females compared to males. Thus, gender differences were present in the effect of
      LPS on vascular responses. LPS induced a greater inhibition of depolarization by
      potassium chloride, but not receptor-activated contractions, in aortic rings from
      female verus male rats.

PMID- 12192894
TI  - Clinical and endocrinological effects of 6 months of metformin treatment in young
      hyperinsulinemic patients affected by polycystic ovary syndrome.
AB  - Most patients with polycystic ovary syndrome (PCOS) have hyperinsulinemia; thus
      it has been postulated that insulin-lowering drugs, such as metformin, might be a
      useful long-term choice. We evaluated the effects of 6 months' administration of
      metformin on clinical and endocrine indices in PCOS patients. Forty-two
      hyperinsulinemic women with PCOS were continuously treated with metformin for 6
      months. Gonadotropins, androgens (testosterone and androstenedione), insulin, sex
      hormone binding globulin (SHBG), lipid profile and clinical indices (menstrual
      length, body mass index (BMI), Ferriman-Gallwey score and waist/hip ratio (WHR))
      were studied before and after metformin treatment. All women experienced a
      normalization of menstrual cycle length (reduction rate, 36.9%), a significant
      decrease in luteinizing hormone, insulin and androgen levels and an increase in
      SHBG plasma concentrations, with a concomitant decrease in cycle length and WHR.
      Significant changes were observed in the lipid profile. According to baseline
      androgen levels, patients were divided into two groups: 20 normoandrogenic and 17
      hyperandrogenic women. The greatest decline of androgens, BMI and Ferriman
      Gallwey score was observed in hyperandrogenic patients. Lowering of androgenicity
      was independent of BMI. Significant changes in lipid profile were observed in
      both groups after metformin treatment. These results suggest that metformin is
      effective in decreasing hyperandrogenism, mainly by reducing insulin levels. This
      leads to an improvement of clinical manifestations of PCOS and, in particular, of
      hyperandrogenism.

PMID- 12192896
TI  - Morphometric analyses of endometriotic tissues to determine their grade of
      activity.
AB  - The last revised classification of endometriosis of the American Fertility
      Society takes the extension of endometriotic lesions and the three macroscopic
      appearances of this disease into consideration. The aim of this study was to
      determine whether morphometric analyses are able to describe the grade of
      activity of endometriotic lesions according to their macroscopic-morphological
      appearances. Endometriotic samples of 45 patients were analyzed morphometrically
      using a semiautomatical planimeter. Six different parameters were investigated:
      the cytoplasmic surface of epithelial cells, the nucleus surface of epithelial
      cells, the nucleus surface of stromal cells, the gland surface, the gland
      circumference and the gland diameter. No statistically significant differences (p
      > 0.05) between the macroscopic appearances of the endometriotic lesions and the
      six analyzed morphometric parameters were found. The majority of the
      endometriotic lesions showed median values for the cytoplasmic surface of
      epithelial cells, the nucleus surface of epithelial cells and the gland surface
      that did not differ from the median values of all tissues, independently of the
      macroscopic appearances of these lesions and of the corresponding serum hormonal
      levels of 17 beta-estradiol and progesterone that were measured at the time of
      biopsy (p > 0.05). Our morphometric data showed that the red and so-called
      'active' endometriotic lesions did not exhibit different morphometric
      characteristics from the so-called 'inactive' black or white lesions. We found
      that white and black lesions showed in some cases higher morphometric values than
      the mean values, so that these macroscopic appearances of endometriotic lesions
      cannot be considered as 'burned-out' endometriotic tissues. Therefore, black or
      white endometriotic lesions also have to be considered as therapeutically
      relevant, as they cannot be defined as 'inactive' endometriosis.

PMID- 12192897
TI  - Development and assessment of the Osteoporosis Index of Risk (OSIRIS) to
      facilitate selection of women for bone densitometry.
AB  - A simple questionnaire would be useful to identify individuals most in need of
      bone mineral density (BMD) testing. We designed a new predictive model and risk
      assessment instrument based on an extensive review of the literature evaluating
      risk factors for osteoporosis, and tested its performance in a large cohort of
      postmenopausal women in whom BMD was measured by dual x-ray absorptiometry. In
      total, 1303 postmenopausal women from an outpatient osteoporosis clinic
      participated in this study. The Osteoporosis Index of Risk (OSIRIS) is based on
      four variables: age, body weight, current hormone replacement therapy use and
      history of previous low impact fracture. The sensitivity and specificity for an
      OSIRIS value of +1 were respectively 78.5% and 51.4%. The AUC under the ROC curve
      of OSIRIS was 0.71. Three categories were arbitrarily created using OSIRIS, with
      cutoff of +1 and -3. The low risk category (OSIRIS > +1) represented 41% of all
      women; only 7% of the women in this category had osteoporosis. The prevalence of
      osteoporosis was very high (66%) among the group at high risk (OSIRIS < -3
      representing 15% of all women). The prevalence of osteoporosis was 39% in the
      intermediate risk group (-3 < OSIRIS < +1, 44% of all women). In conclusion,
      OSIRIS is a simple index based on four easy-to-collect variables from
      postmenopausal women, it shows a high degree of accuracy, and performed well for
      classifying the degree of risk of osteoporosis in western European women of
      Caucasian lineage. Based on this instrument it is possible to propose a strategy
      that would initiate treatment in women with very high risk, postpone BMD
      measurement in women with low risk and limit BMD measurement to women with
      intermediate risk of osteoporosis, this would spare more than 55% of the
      densitometry bill compared with a mass screening scenario.

PMID- 12192898
TI  - Calibration of pesticide leaching models: critical review and guidance for
      reporting.
AB  - Calibration of pesticide leaching models may be undertaken to evaluate the
      ability of models to simulate experimental data, to assist in their
      parameterisation where values for input parameters are difficult to determine
      experimentally, to determine values for specific model inputs (e.g. sorption and
      degradation parameters) and to allow extrapolations to be carried out. Although
      calibration of leaching models is a critical phase in the assessment of pesticide
      exposure, lack of guidance means that calibration procedures default to the
      modeller. This may result in different calibration and extrapolation results for
      different individuals depending on the procedures used, and thus may influence
      decisions regarding the placement of crop-protection products on the market. A
      number of issues are discussed in this paper including data requirements and
      assessment of data quality, the selection of a model and parameters for
      performing calibration, the use of automated calibration techniques as opposed to
      more traditional trial-and-error approaches, difficulties in the comparison of
      simulated and measured data, differences in calibration procedures, and the
      assessment of parameter values derived by calibration. Guidelines for the
      reporting of calibration activities within the scope of pesticide registration
      are proposed.

PMID- 12192899
TI  - Computational chemistry study of the environmentally important acid-catalyzed
      hydrolysis of atrazine and related 2-chloro-s-triazines.
AB  - Many chlorine-containing pesticides, for example 2-chloro-s-triazines, are of
      great concern both environmentally and toxicologically. As a result, ascertaining
      or predicting the fate and transport of these compounds in soils and water is of
      current interest. Transformation pathways for 2-chloro-s-triazines in the
      environment include dealkylation, dechlorination (hydrolysis), and ring cleavage.
      This study explored the feasibility of using computational chemistry,
      specifically the hybrid density functional theory method, B3LYP, to predict
      hydrolysis trends of atrazine (2-chloro-N4-ethyl-N6-isopropyl-1,3,5-triazine-2,4
      diamine) and related 2-chloro-s-triazines to the corresponding 2-hydroxy-s
      triazines. Gas-phase energetics are described on the basis of calculations
      performed at the B3LYP/6-311++G(d,p)//B3LYP/6-31G* level of theory. Calculated
      free energies of hydrolysis (delta h G298) are nearly the same for simazine (2
      chloro-N4,N6-diethyl-1,3,5-triazine-2,4-diamine), atrazine, and propazine (2
      chloro-N4,N6-di-isopropyl-1,3,5-triazine-2,4-diamine), suggesting that hydrolysis
      is not significantly affected by the side-chain amine-nitrogen alkyl
      substituents. High-energy barriers also suggest that the reactions are not likely
      to be observed in the gas phase. Aqueous solvation effects were examined by means
      of self-consistent reaction field methods (SCRF). Molecular structures were
      optimized at the B3LYP/6-31G* level using the Onsager model, and solvation
      energies were calculated at the B3LYP/6-311++G(d,p) level using the isodensity
      surface polarizable continuum model (IPCM). Although the extent of solvent
      stabilization was greater for cationic species than neutral ones, the full extent
      of solvation is underestimated, especially for the transition state structures.
      As a consequence, the calculated hydrolysis barrier for protonated atrazine is
      exaggerated compared with the experimentally determined one. Overall, the
      hydrolysis reactions follow a concerted nucleophilic aromatic substitution (SNAr)
      pathway.

PMID- 12192900
TI  - Group effects on insecticide toxicity in workers of the Formosan subterranean
      termite, Coptotermes formosanus Shiraki.
AB  - Coptotermes formosanus workers were treated topically with insecticide and
      subsequently held individually or in groups to examine possible effects on
      insecticide toxicity. Chlorpyrifos, cypermethrin and chlordane toxicities were
      1.4-, 1.5-, and 1.3-fold greater, respectively, among workers held in groups
      compared with those held individually after insecticide treatment. Experiments
      were conducted to examine how enhanced toxicity occurred among termites held in
      groups after topical insecticide treatment. When workers were treated topically
      with chlordane and immediately placed with untreated workers, significantly
      greater numbers of untreated workers were killed compared with controls at all
      ratios examined (insecticide-treated:untreated). These data indicated that
      workers treated topically with insecticide were capable of somehow transferring a
      lethal dose of insecticide to untreated workers confined in the vial. Chlordane
      was recovered from untreated workers which had been confined with chlordane
      treated workers; significantly higher quantities of chlordane were recovered from
      dead workers exposed to chlordane-treated workers compared with surviving workers
      exposed to chlordane-treated workers. Possible mechanisms of insecticide transfer
      from insecticide-treated to untreated termites are discussed.

PMID- 12192901
TI  - Aerosolized essential oils and individual natural product compounds as brown
      treesnake repellents.
AB  - Chemical irritants useful as repellents for brown treesnakes (Boiga irregularis)
      were identified. Exposure to various compounds produced a range of intensities
      for locomotory behavior in snakes. Essential oils comprised of 10 g liter-1
      solutions of cedarwood, cinnamon, sage, juniper berry, lavender and rosemary each
      were potent snake irritants. Brown treesnakes exposed to a 2-s burst of aerosol
      of these oils exhibited prolonged, violent undirected locomotory behavior. In
      contrast, exposure to a 10 g liter-1 concentration of ginger oil aerosol caused
      snakes to locomote, but in a deliberate, directed manner. We also tested specific
      compounds, all derivative of food and flavor ingredients. 10 g liter-1 solutions
      delivered as aerosols of m-anisaldehyde, trans-anethole, cineole, cinnamaldehyde,
      citral, ethyl phenylacetate, eugenol, geranyl acetate or methyl salicylate all
      acted as potent irritants for brown treesnakes. The individual ingredients were
      classified using cluster analysis into groups that promoted different levels of
      response by snakes. This study is the first to systematically investigate the
      irritant potential of natural products for snakes. These data will be useful in
      the development of practical pest management tools for snakes.

PMID- 12192902
TI  - Assessment of relevant factors and relationships concerning human dermal exposure
      to pesticides in greenhouse applications.
AB  - Principal component analysis (PCA) was applied to the gas chromatographic data
      obtained from 23 different greenhouse trials. This was used to establish which
      factors, including application technique (very small, small, medium and large
      drop-size), crop characteristics (short/tall, thin/dense) and pattern application
      of the operator (walking towards or away from the treated area) are relevant to
      the dermal exposure levels of greenhouse applicators. The results showed that the
      highest exposure by pesticides during field applications in greenhouses, in the
      climatic conditions and in the crop conditions typical of a southern European
      country, occurs on the lower legs and front thighs of the applicators. Similar
      results were obtained by hierarchical cluster analysis (HCA). Drop-size seems to
      be very important in determining total exposure, while height and density of
      crops have little influence on total exposure under the conditions of the present
      study. No pesticide type is a major factor in total exposure. The application of
      multiple regression analysis (MRA) allowed assessment of the relationships
      between the pesticide exposure of the less affected parts of the body with the
      most affected parts.

PMID- 12192903
TI  - High level methoprene resistance in the mosquito Ochlerotatus nigromaculis
      (Ludlow) in central California.
AB  - In the summer of 1998, failures of methoprene field applications to control the
      mosquito Ochlerotatus nigromaculis (Ludlow) were noticed in several pastures in
      the outskirts of Fresno, California, USA. Effective control with methoprene had
      been achieved for over 20 years prior to this discovery. Susceptibility tests
      indicated that the Fresno Oc nigromaculis populations had developed several
      thousand-fold higher LC50 and LC90 tolerance levels to methoprene compared with
      methoprene-naive populations. The synergists piperonyl butoxide (PBO), S,S,S
      tributyl phosphorotrithioate and 3-octylthio-1,1,1-trifluoro-2-propanone had
      little synergistic effect, suggesting that the mechanism of methoprene tolerance
      was not mediated by P450 monooxygenase or carboxylesterase enzyme degradation. As
      part of initiating a resistance management strategy, partial reversion back to
      methoprene susceptibility was achieved in a resistant population after six
      consecutive applications of Bacillus thuringiensis israelensis Goldberg & Marga
      coupled with two oil and two pyrethrum + PBO applications.

PMID- 12192904
TI  - In vivo and in vitro metabolism of fipronil by larvae of the European corn borer
      Ostrinia nubilalis.
AB  - In vivo and in vitro metabolism of [14C]fipronil was examined in a susceptible
      European corn borer (Ostrinia nubilalis, Hubner) laboratory strain. [14C]Fipronil
      penetrated the larval integument slowly, with 71.5% of the applied radioactivity
      recovered from surface rinses 24 h after topical application. Despite this slow
      penetration, radioactivity was detected in both the excrement and internal organo
      soluble fractions. Radioactivity in the internal aqueous fraction and tissue
      pellet accounted for less than 0.8% of total radioactivity. The in vivo studies
      suggest that fipronil oxidation to its sulfone metabolite is the major route of
      metabolic conversion. In vitro studies were performed using subcellular
      microsomal fractions isolated from European corn borer larval midguts. Cytochrome
      P450-dependent monooxygenase activity (methoxyresorufin O-demethylase) was
      consistently observed in midgut preparations, and formation and detection of the
      sulfone metabolite in the same midgut preparations was also NADPH-dependent and
      inhibited by piperonyl butoxide. In vitro metabolism results indicate microsomal
      monooxygenases are responsible for the conversion of fipronil to its sulfone form
      in the European corn borer.

PMID- 12192906
TI  - Field-simulator studies of insecticide resistance to dimethylcarbamates and
      pyrethroids conferred by metabolic- and target site-based mechanisms in peach
      potato aphids, Myzus persicae (Hemiptera: Aphididae).
AB  - A range of insecticides was applied at recommended application rates against
      populations of Myzus persicae (Sulzer) carrying various combinations of three
      insecticide resistance mechanisms (carboxylesterase-based metabolic resistance
      and two target-site mechanisms, known as MACE and kdr), supported on either
      Chinese cabbage or potatoes in field simulator cages. Patterns of response were
      similar on both host species. MACE conferred extreme resistance to pirimicarb and
      triazamate (dimethylcarbamate insecticides). The kdr mechanism was associated
      with resistance to lambda-cyhalothrin, cypermethrin and deltamethrin (pyrethroid
      insecticides). A mixture of pirimicarb plus lambda-cyhalothrin was only effective
      against M persicae not carrying kdr or carrying kdr and low carboxylesterase
      based resistance. None of the insecticides tested was effective against M
      persicae carrying both MACE and kdr resistance. The implications of these
      findings for the formulation of control strategies, based on regular monitoring
      of resistance genotype frequencies, are discussed.

PMID- 12192905
TI  - Bioassay and field-simulator studies of the efficacy of pymetrozine against peach
      potato aphids, Myzus persicae (Hemiptera: Aphididae), possessing different
      mechanisms of insecticide resistance.
AB  - Twenty-one clones of the peach-potato aphid, Myzus persicae (Sulzer), carrying
      various combinations of known mechanisms of insecticide resistance were assessed
      for their response to the new pyridine azomethine compound, pymetrozine, in leaf
      dip bioassays. Pymetrozine was also applied as a foliar spray to populations of
      four different UK M persicae clones on potato plants in field-simulator chambers.
      Neither study showed any evidence of cross-resistance to this compound.
      Pymetrozine, used in conjunction with other effective aphicides, such as
      pirimicarb and imidacloprid, can therefore play an important role in insecticide
      resistance-management strategies for M persicae.

PMID- 12192907
TI  - Laboratory evaluation of two novel strategies to control first-instar gypsy moth
      larvae with spinosad applied to tree trunks.
AB  - Two strategies for controlling first-instar larvae of gypsy moth (Lymantria
      dispar (L)), insecticidal bait and contact insecticide applied directly to the
      tree trunk, were evaluated in the laboratory. Spinosad was selected as a
      candidate natural-product insecticide that is active both by contact and
      ingestion. Incorporated into artificial diet-based bait, spinosad was toxic to
      neonate larvae with a minimal 10-s feeding period, with an LC50 value of 20 (15
      26, 95% confidence interval) mg liter-1. It was significant that neonate larvae
      did not discriminate between spinosad-treated and control diet. Efficacy of diet
      based bait in the laboratory, however, was significantly impacted by previous
      exposure to diet; fed larvae did not stop at the bait and did not incur
      mortality, as compared to unfed larvae. Oak bark was a suitable substrate from
      which neonate larvae could contact spinosad residues. Spinosad applied directly
      to oak bark resulted in significant mortality after 1- and 4-min crawling contact
      exposure times (LC50 = 24 [20-29, 95% CI] and 8.7 [6.9-11, 95% CI] mg liter-1,
      respectively) and contact activity persisted for 2 weeks. While contact activity
      was more potent on glass surfaces than on oak bark, the LC50 values differed only
      by factors of 2.4 and 3.6, for 1- and 4-min exposures respectively.

PMID- 12192908
TI  - Studies on a new group of biodegradable surfactants for glyphosate.
AB  - The effectiveness of a homologous series of biodegradable rapeseed oil
      derivatives (triglyceride ethoxylates; Agnique RSO series containing an average
      of 5, 10, 30 and 60 units of ethylene oxide (EO) as adjuvants for foliage
      applied, water-soluble, systemic active ingredients was evaluated employing
      glyphosate as an example. Previous experiments had revealed that the surfactants
      used are not phytotoxic at concentrations ranging from 1 to 10 g litre-1. The
      experiments were performed using Phaseolus vulgaris L and nine selected weed
      species, grown in a growth chamber at 25/20 (+/- 2) degrees C day/night
      temperature and 40/70 (+/- 10)% relative humidity. The surfactants were evaluated
      for enhancement of spray retention, and foliar penetration biological efficacy of
      glyphosate. Glyphosate was applied at a concentration of 43 mM. The surfactants
      were added at concentrations of 1 g litre-1. The commercial glyphosate 360 g AE
      litre-1 SL Roundup Ultra and unformulated glyphosate served as references. The
      surfactants used improved spray retention, foliar penetration and biological
      efficacy. Some of the formulations were comparable to the performance of Roundup
      Ultra in the aspects evaluated; some were even more effective in enhancing spray
      liquid retention and promoting glyphosate phytotoxicity in several plant species.
      In these studies Agnique RSO 60 generally was most effective.

PMID- 12192909
TI  - Broad-spectrum insecticide resistance in obliquebanded leafroller Choristoneura
      rosaceana (Lepidoptera: Tortricidae) from Michigan.
AB  - Nineteen insecticides, belonging to nine chemical classes, were bioassayed by
      dietary exposure against two strains of obliquebanded leafroller, Choristoneura
      rosaceana, collected from Michigan apple orchards. Berrien is a putatively
      organophosphate-resistant strain from a commercial orchard with a history of
      insecticide use, and Kalamazoo a susceptible strain from an isolated and
      unsprayed orchard. The Berrien strain was moderately resistant (about 25-fold) to
      organophosphates such as azinphos-methyl and chlorpyrifos. Very low resistance (<
      10-fold) was also observed to pyrethroids such as cypermethrin, zeta
      cypermethrin, bifenthrin, deltamethrin and esfenvalerate, to the ecdysone
      agonists tebufenozide and methoxyfenozide, and to the chlorinated pyrrole
      chlorfenapyr. Endosulfan and carbamates such as thiodicarb, methomyl and carbaryl
      had low intrinsic toxicities against both strains, with little difference in
      sensitivity between them. There was no resistance to spinosad. Emamectin benzoate
      was found to be the most toxic insecticide against C rosaceana, with slightly
      higher lethal doses required for the Berrien strain. Unexpectedly, Berrien
      exhibited a very high level of resistance (> 700-fold) to indoxacarb, which has
      never been used in Michigan to control this insect pest. The active metabolite of
      indoxacarb, DCJW, was considerably more toxic than the parent compound, but the
      resistance against DCJW was comparable to that seen with indoxacarb. This
      indicates that a failure to activate indoxacarb was not the mechanism of
      resistance in Berrien. The low level of resistance to several chemistries
      recorded in Michigan C rosaceana can be managed at this stage by adopting a
      rotation of chemistries having different modes of action.

PMID- 12192910
TI  - Disruption of responses to pheromone by (Z)-11-hexadecenyl trifluoromethyl
      ketone, an analogue of the pheromone, in the cabbage armyworm Mamestra brassicae.
AB  - The effects of (Z)-11-hexadecenyl trifluoromethyl ketone (Z11-16:TFMK) a
      fluorinated pheromone analogue, on the responses to sex pheromone of the male
      cabbage armyworm, Mamestra brassicae, have been investigated in an actograph and
      by electroantennography (EAG). In spite of its structural proximity with the
      natural pheromone, Z11-16:TFMK was poorly active in EAG, and not active on male
      behaviour. When permeated in the air, Z11-16:TFMK reversibly inhibited the
      electroantennographic responses to (Z)-11-hexadecenyl acetate (Z11-16:Ac), the
      main component of the sex pheromone. In the actograph, the latency of the
      activation was increased and the intensity of the behavioural activity of males
      in response to Z11-16:Ac was significantly reduced in the presence of Z11
      16:TFMK. These results, along with others previously reported by us, provide new
      pointers to the possible use of Z11-16:TFMK in pest-control strategies.

PMID- 12192911
TI  - Photochemical behaviour of dichlorprop [(+/-)-2-(2,4-dichlorophenoxy)propanoic
      acid] in aqueous solution.
AB  - Aqueous solutions of dichlorprop were irradiated under different conditions of
      pH, wavelength and oxygenation. The photochemical behaviour was found to be
      complex and many photoproducts were formed. However, at low concentrations the
      main photoproducts were 4-chloropyrocatechol, 2-chlorophenol, 4-chlorophenol and
      2,4-dichlorophenol. Some other photoproducts were identified, namely 2-(4-chloro
      2-hydroxyphenoxy)propanoic acid, 2-(3,5-dichloro-2-hydroxyphenyl)propanoic acid
      and 2,4-dichlorophenyl acetate. From comparison with results previously obtained
      with mecoprop [2-(4-chloro-2-methylphenoxy)propanoic acid] it appears that the
      presence of a chlorine atom in position 2 on the ring strongly modifies the
      photochemical behaviour.

PMID- 12192912
TI  - Understanding HIPAA: an update.

PMID- 12192913
TI  - Timely payment legislation.

PMID- 12192914
TI  - Well-defined unilocular radiolucency.
AB  - Clinical and radiographic features provide significant clues for diagnosis of a
      traumatic bone cyst, which should be confirmed surgically to avoid unnecessary
      endodontic treatment or radical surgery due to a misdiagnosis. Management of the
      traumatic bone cyst is generally accomplished by the diagnostic process of
      surgical exploration. Reports of unusual clinical courses and an inadequate
      understanding of the etiology indicate that careful follow-up is essential.

PMID- 12192915
TI  - The pulpectomy in primary teeth.
AB  - BACKGROUND: The pulpectomy is an underutilized treatment modality for severely
      infected primary teeth. CASE DESCRIPTION: The author presents two pulpectomy
      cases that were filled with Vitapex. CLINICAL IMPLICATIONS: Vitapex is an
      excellent filling material for primary tooth pulpectomies. Its clinical
      characteristics and ease of use may make the pulpectomy procedure a more
      attractive alternative to extraction.

PMID- 12192916
TI  - What you should know about mandatory CDE.

PMID- 12192917
TI  - [Anatomico-surgical contribution to the knowledge of the lymphatic spread of
      gastric adenocarcinoma].
AB  - Following the researches performed on lymphatic spread of gastric carcinoma, our
      study aimed to add useful informations to establish the extension of exeresis
      with radical intent on the basis of recent studies on sentinel node mapping. The
      study includes 120 consecutive cases of gastric cancer operated between 1996 and
      2000. Sixty-nine (57.5%) males and 51 (42.5%) females, with age ranging between
      29 and 84 years, were evaluated. Cancer location was in 17 patients upper third,
      in 35 middle third, in 59 distal third and in 9 cases gastric stump. Early cases
      (T1-2) were 65 and advanced cases (T3-4) were 55. Sixty-eight STG and 52 TG were
      performed with 21 D1, 73 D2 and 26 D3 lymphoadenectomy. Overall 3501 lymph-nodes
      were examined. Eighty-two cases (68%) showed lymph-nodal metastases, while 38
      (32%) were negative. The lymphatic spread of gastric cancer resulted related to
      the depth of wall invasion (T): 25% of T1, 75% of T2, 85% of T3 and 95% of T4
      were node positive (N+). The correlation between T and N+ was also significative
      concerning the diffusion to the first, second and third level stations,
      increasing with the depth of wall invasion. The possibility of extension to one
      single lymphnodal station was inversely related to the T. When the first level
      stations were negative the second and third were never positive. This study seems
      to confirm the complex but systematic and predictable lymphatic gastric flow. The
      skip metastases, rare but described in other retrospective studies, were never
      observed. Our study shows that sentinel node mapping could be reliable also for
      gastric cancer surgery, allowing tailored and less aggressive resections.
      Meanwhile, from this analysis it appears that nodal stations 7-8 should be
      included in the first level lymphoadenectomy, widening D1 exeresis considered
      until now sufficient in less advanced cases. In conclusion, studies of lymphatic
      spread and sentinel node mapping seems to require a different therapeutic
      approach to gastric cancer concerning D1 lymphoadenectomy, tailoring the exeresis
      on the basis of sentinel node mapping in negative T1-2 cases, but systematically
      widening the lymphoadenectomy from the perigastric only, to 7 and 8 stations.

PMID- 12192918
TI  - One-stage treatment of obstructing colorectal cancer.
AB  - Large bowel obstruction is due to colorectal carcinoma in 90% of cases. The
      optimal management of obstructing left colonic carcinoma is still a controversial
      matter. The aim of this retrospective study was to evaluate the indications for
      one-stage treatment of obstructing colorectal cancer. Over the period from
      January 1998 to June 2001, 17 patients were operated on in our department for
      obstructing colorectal cancer. Twelve patients underwent a one-stage emergency
      operation by immediate anastomosis without diversion, while five patients were
      managed palliatively. We performed resection and primary anastomosis following
      intraoperative irrigation in obstructing sigmoid cancer lacking colonic wall
      lesions, while subtotal colectomy was carried out in cases of massively distended
      colon with ischaemic lesions and in patients with good anal continence. Colostomy
      treatment was indicated only in high-risk patients with unresectable lesions. The
      authors believe that, in cases of obstructing left colorectal cancer, an
      experienced, skilled surgeon can perform one-stage resection and anastomosis on
      patients in good general condition. On the other hand, a defunctioning colostomy
      may be ideal for surgeons with little experience in colorectal surgery and in
      patients with a very poor prognosis.

PMID- 12192919
TI  - [Local excision of rectal tumors].
AB  - Local excision is a suitable approach for treating sessile adenomas and early
      adenocarcinomas of the rectum. The indication for transmural rectal carcinomas
      (T2 and T3) is a matter of debate and no randomized studies have been reported to
      date. The early and long-term results of a consecutive series of 160 patients who
      underwent local excision in our departments are reported. Sixty-three patients
      (39%) had adenoma and 97 patients (61%) carcinoma. Forty-seven patients with
      carcinoma (48%) received adjuvant therapy. Postoperative complications occurred
      in 25 patients (15%). The complication rates were 13% (8/63) for adenomas and 18%
      (17/97) for carcinomas. Only 1 patient died during the postoperative period as a
      result of unrelated causes. The overall local recurrence rates were 3% and 24%,
      respectively. Among the adenocarcinomas recurrence was related to staging, tumour
      clearance at the resection margins and use of chemo- and radiotherapy. No
      recurrences were reported among the T2 patients submitted to neoadjuvant
      treatment. A difference versus radical surgery was observed for T3 patients only.
      Local excision and transanal endoscopic microsurgery in particular is worthwhile
      in adenomas and T1 carcinomas of the rectum. Patients with T2 tumors should be
      treated with preoperative chemo- and radiotherapy. Patients with T3 tumors should
      be treated with transanal endoscopic microsurgery for palliative purposes only.

PMID- 12192920
TI  - [Esophagectomy by video-assisted laparoscopic and trans-mediastinal approach].
AB  - The aim of study was to report our experience with an original technique of
      oesophagectomy without thoracotomy. The operation consists of two complementary
      approaches. Laparoscopic access enables the surgeon to mobilize the stomach and
      dissect the distal oesophagus. Cervical access allows dissection of the upper
      thoracic oesophagus under vision using a special videomediastinoscope. Six
      patients with oesophageal carcinoma or high-grade dysplasia in Barrett's
      oesophagus were selected for this operation over the period from October 2000 to
      December 2001. The operation was completed by minimally invasive access in 4 of
      the 6 patients. The mean duration of the operation was 240 minutes, and the
      postoperative hospital stay 9.5 days. One patient required endoscopic pneumatic
      dilatation of the pylorus 2 weeks after surgery. This technique enhances the
      safety of conventional oesophagectomy without thoracotomy by avoiding the "blind"
      dissection of the upper mediastinum. The advantages of laparoscopy include
      superior staging of the disease, gastric mobilization, and lymphadenectomy of the
      lower mediastinum. The ideal candidates for this operation are patients with high
      grade dysplasia or T1-N0 adenocarcinoma arising from Barrett's oesophagus.

PMID- 12192921
TI  - Analysis of factors influencing the diagnostic failure of intraoperative fine
      needle aspiration cytology in pancreatic cancer.
AB  - Intraoperative fine-needle aspiration cytology (IFNAC) of pancreatic lesions
      provides a safe method of rapid tissue diagnosis. Few studies have included a
      thorough statistical analysis of the factors influencing the diagnostic failure
      of IFNAC. IFNAC was performed on 196 patients during surgical procedures for
      pancreatic and periampullary masses over an 18-year period. The sensitivity was
      90.6% and the specificity 100%. There was a 0% puncture-related complication
      rate. In all, 6 clinicopathological factors were analyzed to elucidate
      correlations, if any, with IFNAC failure using statistical analysis. Statistical
      analysis of each of these clinicopathological factor showed that the cases of
      failure tended to be related to small tumour size (P < 0.0001), well
      differentiated grading (P < 0.002) and a nuclear size similar to the surrounding
      RBCs (P < 0.0001). Age, gender, moderately or poorly differentiated tumours, and
      multiple punctures proved to be of no statistical significance in our analysis.
      We suggest that diagnostic failure of IFNAC seems to be caused mainly by a
      structural factor such as tumour size and an intrinsic one (a cellular low
      atypism factor such as well-differentiated grading and small nuclear size).
      However, we would caution that negative IFNAC cannot be relied on to definitively
      exclude a diagnosis of carcinoma and, in many instances, the justification for
      pancreatic resection cannot always be based on cytologic findings, but rather on
      clinical and laparotomy findings.

PMID- 12192922
TI  - [Laparoscopic splenectomy: analysis of 60 consecutive cases].
AB  - The purpose of the study was to analyze the results of 60 patients who were
      candidates for laparoscopic splenectomy. Over the period from May 1994 to May
      2001, 60 patients were candidates for splenectomy. Laparoscopy was
      contraindicated in 3 cases because of ASA III and marked splenomegaly (2 cases)
      and previous gastric resection (1 case). The procedure was indicated for benign
      disease in 38 cases and for malignant disease in the remainder. Fifty-three
      procedures were completed laparoscopically (92.9%). Conversion proved necessary
      in 4 patients (6.7%) due to large incisional hernia, perisplenic abscess,
      bleeding of major splenic vessels at the hilum and marked splenomegaly (2 cases
      of lymphoma). The mean operative time was 200 min for the malignancies and 110
      min for the benign conditions (P < 0.05). Major morbidity occurred in 5 cases
      (8.7%). No deaths were registered. The mean postoperative hospital stay was 7.5
      days for patients with malignancies and 5.2 days for patients with benign disease
      (P < 0.05). Laparoscopic splenectomy was safe and effective in patients with
      benign disease, even in cases of marked splenomegaly. The morbidity rate was
      significantly higher in lymphoma patients than in patients with benign
      haematological disorders.

PMID- 12192923
TI  - [Splenic traumas: indications and limitations of conservative treatment].
AB  - According to the experience of the authors, comparison between two consecutive
      periods (1980-1994 and 1995-2000) has shown a substantial increase in splenic
      traumas simply treated by observation and monitoring. Their number in fact has
      risen significantly from 5 to 32. This has allowed a rise in the overall
      percentage of spleen conservation, which has increased from 16.4% to 52.9%. On
      the contrary, a reduction in surgical conservative operations has been observed,
      the number decreasing from 19 to 4. Such treatments require the same clinical
      conditions as non- operative treatments, but the latter have to be accompanied by
      efficient organization of intensive care and monitoring, in which surgeons and
      anesthesists, who are familiar with all the aspects of the problem, collaborate
      efficiently. Since this kind of organization has been achieved, the number of
      patients successfully treated without surgery has increased significantly. In a
      sample of 37 patients receiving non-surgical conservative treatment, the
      percentage of delayed splenectomies was as low as 5.4%.

PMID- 12192925
TI  - [Surgical physiopathology of the inguinal region].
AB  - Bassini's procedure is based on the pivotal role played by the transversalis
      fascia in inguinal containment. The other important constituent of inguinal
      reinforcement is the flax inguinalis, which forms the curved upper edge of the
      "inguinal hiatus", whose base is formed by the inguinal ligament. This hiatus
      closes or contracts when the intra-abdominal pressure increases. It is clear that
      if the muscles are strong this action will be effective in containing the wall.
      By contrast, the more relaxed the inguinal cleft is, the more ineffective this
      action may become. Weakness of the muscular-aponeurotic structure thus becomes
      all the more important. Two systems are therefore available to contain the
      inguinal hiatus: the transversalis fascia and the falx inguinalis. Under normal
      conditions, they act synergistically to contain the wall. The relevance of the
      function of each, however, is debatable. With Bassini's repair, containment is
      assured if the transversalis fascia is used, i.e., if a true "triple layer"
      operation is performed. Procedures such as Lichtenstein's do not act upon the
      transversalis fascia: if this is weak or perforated, abdominal pressure weighs on
      the prosthesis. Moreover, a mesh that is not well attached may lead to
      recurrence. The crucial role of the transversalis fascia is proved by procedures
      with preperitoneal mesh prostheses. In these procedures, performed with
      videolaparoscopic techniques or according to Stoppa's or Rives' methods, or even
      with an inguinal preperitoneal mesh (as in a series of ours treated with positive
      results), the repair involves only the transversalis fascia. These repair
      procedures confirm the superiority of the transversalis fascia procedure in
      assuring inguinal containment.

PMID- 12192924
TI  - Gastric cancer: prognostic significance of the Goseki histological
      classification.
AB  - The aim of this study was to evaluate the prognostic significance of the Goseki
      factor in patients undergoing potentially curative resection for gastric cancer.
      From 1989 to 1999 202 patients with gastric cancer came in for observation to the
      Ist Surgical Clinic of Catania University. For the purposes of this study we
      examined 86 patients with a 5-year follow-up, from whom it was possible to obtain
      samples which were mounted in paraffin blocks and stained (haematoxylin-eosin and
      PAS-Alcian blue). The 5-year survival rates of patients with Goseki I and II
      tumours with good tubular differentiation were 90% and 30% as compared with 42%
      and 32% in patients with tumours that showed poor tubular differentiation (Goseki
      III and IV). In contrast, the 5-year survival rates in patients with mucin-poor
      tumours (Goseki I and III) were 90% and 42%, as against 30% and 32% in patients
      with mucin-rich tumours (P < 0.05). Our conclusion is that of the two components
      of the Goseki system, i.e. tubular differentiation and intracellular mucus, mucus
      production was found to be the more important determinant of clinical outcome.
      Mucus production has a greater impact on survival than the degree of tubular
      differentiation and is independent of it.

PMID- 12192926
TI  - [Treatment of inguinal hernia: a prospective study comparing Bassini's procedure,
      the inguinal pre-peritoneal prosthesis and the Lichtenstein technique].
AB  - Inguinal hernia surgery has aroused considerable interest in recent years, with
      numerous advances being proposed to treat these disorders. Bassini's procedure,
      based on the importance of the transversalis fascia as a fundamental containment
      mechanism, was for many years the treatment of choice for inguinal hernia. In our
      study, covering eight years of activity, we focused our attention on this
      principle, comparing repair procedures such as Bassini's and those with a
      preperitoneal mesh, in which the repair involves the transversalis fascia, with
      procedures based on Lichtenstein's technique in which the fascia is left intact.
      The investigation protocol was thus based on the performance of the three
      techniques in parallel by the same surgical team. The parameters of immediate
      complications, lasting pain and recurrence were used to evaluate the results. The
      first two occurred infrequently in all groups (a greater incidence was seen with
      mesh procedures). Recurrence rates after preperitoneal mesh techniques were
      extremely low, confirming the paramount functional importance of the
      transversalis fascia. The results of our analysis substantiate the advantage of
      employing the preperitoneal mesh technique, which opens up new horizons for the
      treatment of recurrent hernia.

PMID- 12192927
TI  - [Radioimmunoguided surgery (R.I.G.S.) in colorectal cancer. Preliminary results].
AB  - The authors describe their experience in utilizing 'ArcitumoMab' and
      radioimmunoguided surgery in a group of patients with localized and advanced
      colorectal cancer. Twenty-one patients were studied who were found to be positive
      to 'ArcitumoMab'. Immunoscintigraphy was obtained in 95% of cases.
      Radioimmunoguided surgery was performed in all cases. One case, which was
      negative at immunoscintigraphy, was found to be positive intraoperatively when
      radioimmunoguided surgery was performed. Radioimmunoguided surgery, in the
      authors' view, is a useful technique but needs to be validated in larger samples,
      particularly in cases of relapse.

PMID- 12192928
TI  - [Pancreatic pseudocysts: endoscopic treatment. Personal experience].
AB  - Pseudocyst is a complication of acute and chronic pancreatitis. Today endoscopic
      drainage is reported as being the treatment of choice for these complications.
      Endoscopic drainage was performed in 15 patients with a pseudocyst bulging into
      stomach or duodenal lumen as detected by CT and endoscopic examination. All 15
      cases treated from January 1991 to December 2001 (11 men, 4 women; median age:
      55.7 years [range: 33-81] were successfully drained. The mean hospital stay was
      4.8 days. No mortality or major complications were observed and the compliance
      was very good. The procedure is safe and we believe that endoscopic drainage
      should be the procedure of choice for pseudocysts which bulge into the
      gastrointestinal lumen.

PMID- 12192929
TI  - Videothoracoscopic evaluation of thoracic injuries.
AB  - Residual thoracic collections after thoracic traumas occur in 5-30% of patients
      and are a major risk factor for development of empyema. Management with a
      thoracostomy tube is the traditional treatment but it requires a prolonged
      hospital stay and 20% of patients treated continue to have a residual clot. Forty
      two haemodynamically stable patients with chest trauma (36 blunt and 6
      penetrating) were examined thoracoscopically. Indications for videothoracoscopy
      included suspected diaphragmatic injury (8 patients), persistent pneumothorax
      (8), continued haemorrhage (6) and clotted haemothorax (20). Diaphragmatic
      lacerations were confirmed thoracoscopically in 7 patients. Four of them were
      successfully repaired with thoracoscopic techniques and three were repaired after
      conversion to open thoracotomy for large diaphragmatic lacerations. In patients
      with persistent pneumothorax, limited lung lacerations were correctly diagnosed
      and repaired thoracoscopically. In all patients with continued haemorrhage
      intercostal artery injury was confirmed and repaired by diathermy. All clotted
      haemothorax cases were successfully evacuated. No complications occurred.
      Videothoracoscopy appears to be a safe, accurate and reliable operative therapy
      for the assessment of diaphragmatic injuries, control of continued bleeding and
      evacuation of clotted haemothorax, reducing the hospital stay and possible
      complications.

PMID- 12192930
TI  - [Our experience with the use of a plastic prosthesis and self-expanding stents in
      the palliative treatment of malignant neoplastic stenoses of the esophagus and
      cardia. Comparative analysis of results].
AB  - Rapid palliation of malignant dysphagia is usually possible by means of the
      endoscopic implantation of a plastic prosthesis, but this device has a high
      morbidity rate. Recently, expandable metal stents have become available and may
      reduce the morbidity and mortality rates. The aim of this retrospective study was
      to evaluate self-expanding metal stents compared with conventional plastic
      prosthesis in malignant strictures of the oesophagus and cardia. One hundred and
      thirteen endoscopic tube implantations were carried out in 120 patients with
      malignant stenosis of the oesophagus and cardia using a plastic prosthesis over
      the period 1980-1993 (72 cases) and self-expanding metal stents over the period
      1993-2001 (48 cases). The underlying causes of strictures were oesophageal or
      cardial cancer in 108 cases and oesophageal invasion by lung cancer in 12. The
      indications for endoscopic intubation were advanced tumour stage and/or risk
      factors which made resection inadvisable. The stents used in the conventional
      group were the Celestin pulsion tube in 18, the Atkinson prosthesis in 23 and the
      Wilson-Cook tube in 27, while the Ultraflex stent was always employed in the
      other group. Dysphagia was scored according to the Atkinson and Ferguson
      classification and the preoperative median score (3.6) was comparable in the two
      groups. The technical success rate was 94.4% with the plastic prosthesis (68/72)
      and 93.7% with the self-expanding metal stents (45/48) because in 4 and 3
      patients, respectively, it proved impossible to implant the stent. After
      intubation the dysphagia score was improved in both groups (median score = 0.9)
      and the functional success rates were 85.2% (58/68) and 88.8% (40/45),
      respectively, while 10 and 5 patients showed no improvement of symptoms. The
      early complication rate was 5.9% (4/68) in the conventional stent group (1
      perforation, 2 severe bleedings and 1 stent proximal migration) and nil in the
      other group. Late complications occurred in 14 (20.6%) (7 food obstruction, 4
      neoplastic obstructions and 3 dislodgements) and 9 patients (20%) (3 neoplastic
      obstructions, 1 food obstruction, 3 distal migrations and 2 bleedings),
      respectively, but all the complications were easily corrected. Three deaths
      occurred with the plastic prosthesis (4.4%), while the mortality was nil with the
      metal stents. The median survival times were 183 (range: 58-486) and 151 days
      (range; 25-545), respectively. Our experience suggests that endoscopic placement
      of self-expanding metal stents is effective and safe for the management of
      dysphagia in malignant strictures of the oesophagus and cardia and has to be
      preferred to conventional plastic prostheses for easier implantation. The
      technical and functional success rates are similar in both groups, but the acute
      complication and mortality rates of the Ultraflex prosthesis are lower as
      compared to the traditional prosthesis.

PMID- 12192931
TI  - [Prevalence of the neuroendocrine phenotype in thymus neoplasms].
AB  - To determine the prevalence of neuroendocrine differentiation in human thymic
      neoplasms, which are unusual tumours that may range from well-differentiated to
      overtly malignant, poorly differentiated lesions, an immunohistochemical study
      was conducted in 23 thymic neoplasms re-classified on the basis of the new 1999
      WHO classification. Immunohistochemical evidence of neuroendocrine
      differentiation in the form of reactivity to the markers synaptophysin, neuron
      specific enolase and chromogranin A was found in 6 of 23 tissues (26%). Two of 3
      patients with thymic carcinoids (or well-differentiated thymic neuroendocrine
      carcinoma) were affected by multiple endocrine neoplasia type 1 (MEN-1).
      Myasthenia gravis was present in 2/6 patients with neuroendocrine
      differentiation. This study demonstrates the high prevalence of neuroendocrine
      markers in human thymic neoplasms. Whether and in what percentage of cases
      immunohistochemical reactivity may be correlated with clinical behaviour and
      outcome remains a controversial issue. Finally, the association between thymic
      carcinoids and MEN-1 is a strong indication for clinical and possibly genetic
      screening of all patients presenting this feature, just as all MEN-1 patients
      have to undergo thoracic imaging and prophylactic thymectomy in selected cases.

PMID- 12192932
TI  - [Expression of Lewis carbohydrate antigen in human tumors].
AB  - In this study we show, by immunoblotting, that Mab B3, a newly isolated
      monoclonal antibody, reacts with a variety of glycoproteins with different
      molecular weights expressed in gastric, pancreatic and colorectal cancers. The
      reactivity pattern differed in cancers arising in different tissues, though no
      correlation was observed with the histopathological characteristics of the
      lesions analysed. MAb B3 does not react with liver, brain or kidney cancers and
      has a limited reactivity with lung cancers but reacts very strongly with
      metastatic lesions. Because of the limited reactivity of this antibody with
      normal tissues, MAb B3 genetically fused with toxin in the form of a recombinant
      immunotoxin may be useful in treating certain kinds of cancer such as metastatic
      lesions. However, until current trials are completed, we will not know whether
      this immunotoxin will be helpful in cancer treatment.

PMID- 12192933
TI  - Laparoscopic cholecystectomy in the morbidly obese.
AB  - In the early days of video-assisted laparoscopic cholecystectomy (VLC), obesity
      was considered a contraindication for the procedure. We reviewed charts from 304
      patients undergoing VLC; 90 patients were obese, and among these, according to a
      classification currently used by medical nutritionists and based on BMI, 45 were
      overweight (BMI > or = 25 < or = 29.9), 27 were considered conventionally obese
      (BMI > or = 30 and < 40) and 18 morbidly obese (BMI > or = 40). In this study we
      considered only the morbidly obese patients (5 males and 13 females). The average
      age was 42.3 years (range: 21-65) and the average weight 275 Ib (range: 186-331
      Ib). Six patients had previously undergone abdominal surgery. All patients were
      symptomatic for gallstones, and 5 of them were suffering from acute
      cholecystitis. Mean operative time was 20 minutes (range: 10-45 minutes) longer
      than that of non-obese patients. No open conversion was necessary. No major
      postoperative morbidity and no cases of mortality occurred. The mean hospital
      stay and resumption of normal diet were similar to those of non-obese patients.
      Regardless of the higher postoperative risks after open cholecystectomy in obese
      patients (pulmonary complications, thromboembolism, wound infections and
      cardiovascular complications), we suggest VLC as the procedure of choice for
      cholecystectomy in these patients.

PMID- 12192934
TI  - [Impact of laparoscopic surgery in the treatment of chronic abdominal pain
      syndrome].
AB  - Chronic abdominal pain syndrome is becoming increasingly important with regard to
      the quality of life of the patients and its social and economic impact, in terms
      of cost of hospitalization, income loss due to sick leave, and pharmaceutical
      costs for treatments which fail to offer either significant clinical improvement
      or resolution of the pain symptoms. The main symptom is chronic abdominal pain,
      which may vary in intensity and may be associated with constipation and episodes
      of vomiting, when the clinical picture evolves toward one of subocclusion or
      total occlusion of the bowel. We considered the following criteria in our
      selection of patients for this study: 1) quality of life, 2) constant use of
      antispastic and analgesic medications, 3) absence of any other diagnosticable
      pathology prior to the operation. From August 1992 to April 2000 we operated on
      105 patients with this syndrome (16 males and 89 females). Among these 8 patients
      had never been subjected to a laparotomy, while 97 had previously undergone
      surgical procedures (126 laparotomies). In the first 85 patients in the series
      (81%) we used a 10 mm laparoscope (0-30 degrees) to evaluate the presence of
      abdominal-visceral adhesions based on the type of surgery the patient had
      undergone previously, as well as the location of the pain reported by the
      patient. In 41 cases (48.2%) the pneumoperitoneum was obtained with the Veress
      needle. In another 44 cases (51.8%) the Hasson technique was used. Since June
      1999, we have carried out the exploration of the abdominal cavity in 20 patients
      (19%) using a trocar and 2.2 mm laparoscope in the left hypochondrium along with
      a mini-trocar placed either in the right or left flank. (The positioning of the
      trocars depended on the previous surgical procedures performed). The exploration
      included inspection of the abdominal cavity. In 8 of the patients the procedure
      was carried out under local anaesthesia We performed laparoscopic adhesiolysis in
      93 cases; in 7 cases no signs of adhesions were seen, while in another 5 cases it
      was necessary to convert the original laparoscopic procedure to a laparotomy. The
      types of adhesions found were fine-filmy (46%), dense-vascularised (46%), and
      cohesive (16%). In 6 cases during lysis of the adhesions complications of serous
      muscular lesions occurred, which required laparotomic repair. In 5 cases we
      diagnosed a pathological condition which was not suspected. The average
      postoperative hospital stay was 2 days (range: 1-7); no major postoperative
      complications were noted. In the course of the follow-up of 78 patients over an
      average of 37 months (range: 6-72) the results obtained were as follows; 47
      patients (60.2%) had complete pain relief, 18 patients (23.1%) had partial pain
      relief, and the remaining 13 patients (16.7%) had no significant pain relief.
      Laparoscopic exploration in patients with chronic abdominal pain is technically
      feasible in a simple manner in most patients. By means of careful and accurate
      preoperative selection of the patients partial if not complete pain relief can be
      achieved in a high percentage of cases (83.3% in our series).

PMID- 12192935
TI  - [Role of nutritional support in the treatment of enteric fistulas].
AB  - Enteric fistulas are nowadays considered an important therapeutic challenge.
      Artificial, total parenteral and enteral nutrition have allowed an improvement in
      the healing of these fistulas and a lower incidence of mortality. Fourteen
      patients with enteric fistulas (10 men, 4 women; mean age: 64.4 years; range: 20
      80 years) were observed. The fistula was located in the large bowel in 11
      patients, in the ileum in 2, and in the jejunum in 1. Thirteen patients received
      enteral nutrition. The patient with the jejunal fistula received total parenteral
      nutrition for 30 days and then enteral nutrition. The fistulas were successfully
      treated in 11 patients. One patients underwent surgery after 6 weeks of treatment
      with enteral nutrition because of lack of improvement of the symptomatology. In
      two patients, with advanced cancer of the colon and stomach, respectively, only a
      reduction of the fistula output was achieved. Nutritional support in the
      treatment of enteric fistulas is an effective procedure widely utilised to
      restore adequate nutritional status and bowel rest, which are two important
      targets for achieving fistula closure. Nutritional support is also useful in the
      management of patients undergoing surgery in order to reduce the postoperative
      complication rate.

PMID- 12192936
TI  - [Diverticulosis of the colon: complications of surgical interest].
AB  - Diverticular disease is prevalently only of medical interest. Repeated episodes
      of diverticulitis, particularly in younger patients, and serious complications
      such as perforation, stenosis, fistula and haemorrhage demand surgical treatment.
      The timing and type of surgical operation are conditioned by the pathological
      picture and by the patient's general condition and age. The authors present a
      series of 586 patients admitted for diverticular disease, 84 of whom presented
      complicated diverticulosis. Nineteen cases (22.6%) underwent elective surgery in
      the form of an anterior rectal resection, while 65 of them underwent urgent
      surgery for complicated diverticulosis variously consisting in total colectomy, a
      Hartman's resection, a simple rectal resection or a left or right hemicolectomy.

PMID- 12192937
TI  - [Our experience in the treatment of hemorrhoids and circumferential mucosal
      rectal prolapse using Longo muco-prolapsectomy ].
AB  - The authors report their experience with the treatment of hemorrhoid disease and
      circumferential mucosal rectal prolapse with the use of a mechanical suturing
      device, according to the Longo technique. Over the period from March 98 to
      December 2000, 106 patients were treated with the above-mentioned procedure (100
      patients for haemorrhoids and 6 for circumferential prolapse). Twenty-one
      patients had grade 4, 77 grade 3 and only 2 grade 2 disease. One hundred patients
      were followed up over a median period of 16.5 months (for the group with
      haemorrhoids) and 19 months (for the prolapse group). In 81% of cases the
      procedure was one-day surgery. Mucohaemorrhoidectomy with a stapler was well
      tolerated in terms of severity of postoperative symptomatology: in 42% of the
      patients operated on there was no need for any analgesic treatment. The time to
      return to work was 9.9 days for self-employed subjects and 15.6 days for the
      others. Refinement of the procedure and better patient selection may improve the
      results achieved with this technique. Stapled haemorrhoidectomy may be regarded
      as a sound technique that should be part of the surgeon's armamentarium. We
      suggest an "eclectic" approach whereby the stapling procedure may be included
      among the possible therapeutic options, with a view to optimising the choice of
      therapy for each individual patient.

PMID- 12192938
TI  - Primary angiosarcoma of the breast: a case report.
AB  - Primary angiosarcoma of the breast is a rare entity. The absence of clinical and
      instrumental features is a fundamental concept in the context of diseases of the
      breast. Currently, the most extensively used surgical procedure is simple
      mastectomy with removal of the fascia of the pectoralis major muscle. A 45-year
      old woman presenting this lesion is described here, with particular reference to
      the cytomorphological findings.

PMID- 12192939
TI  - [Pleuro-pancreatic fistula diagnosed by ultrasonography].
AB  - A pleural effusion resulting from pancreatitic-pleural fistula is a rare clinical
      entity which has, however, been more frequently recognised in the last ten years.
      The cause is a fistula tract between the pancreas and the pleura. Elevated
      amylase levels in the pleural fluid are the key to suspecting this diagnosis,
      which needs to be confirmed using imaging techniques such as CT, MRI and
      ultrasound or ERCP, which are necessary for defining the therapeutic strategy.
      After the failure of conservative management, a cysto-jejunostomy with a Roux-en
      Y loop resolved the pleural effusion. This is the surgical technique of choice in
      the presence of a pseudocyst. We report details of a patient with a
      pancreaticopleural fistula diagnosed by ultrasonography, in which CT and ERCP
      were unable to demonstrate any communication between the pleural cavity and the
      pseudocyst. Only one similar case has been reported in the literature, diagnosed
      initially following visualization of a fistula tract at CT. We discuss the
      diagnostic and therapeutic options.

PMID- 12192940
TI  - [Mirizzi syndrome: a case report].
AB  - Mirizzi syndrome is a rare biliary disease caused by compression on the common
      bile duct by a stone located in the gallbladder or cystic duct. In rare cases an
      association with gallbladder carcinoma has been described. The pathogenesis seems
      ascribable to long-term stasis of stones that causes worsening compression on the
      common bile duct. The diagnosis, in the absence of specific symptoms, is usually
      obtained by means of an endoscopic cholangiography or during laparotomy. Proposed
      treatments are surgical or endoscopic. There are rare descriptions of Mirizzi
      syndrome complicated by the presence of gallbladder carcinoma, but no reports of
      Mirizzi syndrome complicated by the incidental retention of a Dormia basket in
      the cystic duct. We report a peculiar case of Mirizzi syndrome associated with
      carcinoma of the gallbladder and complicated by the incidental retention of a
      Dormia basket in the cystic duct, surgically treated with success.

PMID- 12192941
TI  - [Endometriosis of umbilical cicatrix: a case report and review of the
      literature].
AB  - The present report refers to a case of "primitive" endometriosis of the umbilical
      scar in a 50-years-old woman who complained of the appearance at the umbilicus of
      two nodules measuring 7 and 2 mm in diameter. These nodules, which were brownish
      in colour, were responsible for prickly pain and itching unrelated to the
      menstrual cycle. Both nodules were excised after a preoperative non-specific
      diagnosis of granuloma. Pathology findings revealed "cutaneous endometriosis".
      The authors believe that the appearance of a nodular swelling at the umbilicus of
      a woman of child-bearing age should lead to a suspicion of endometriosis among
      the possible diagnoses.

PMID- 12192942
TI  - [Multidisciplinary approach to the patient with multiple trauma: a case report].
AB  - A multidisciplinary approach to severe polytraumatized patient is very important
      for a rapid, uncomplicated recovery. Specialized centres with special beds,
      monitoring equipment, and a multidisciplinary team are required. The authors
      report a case of a 26-year-old man admitted to their department in an emergency
      setting for a crush injury (occupational trauma) of the lumbar, gluteal and
      perineal areas, complicated with septic shock and gas gangrene of the injured
      areas. A multidisciplinary approach to the patient, consisting in surgical and
      plastic surgical therapy, hyperbaric oxygen therapy and the use of a special
      antidecubitus fluidized bed allowed complete recovery within 7 months without any
      motor or sphincter disorders.

PMID- 12192943
TI  - [Wandering spleen with torsion of the pedicle. A case report and review of the
      literature].
AB  - Congenital deficiency or acquired laxity of the suspensory ligaments, that
      usually hold the spleen in place in its compartment, may result in extreme
      splenic mobility. Consequently, this mobility predisposes to torsion of the
      elongated splenic vascular pedicle creating a situation of acute abdomen due to
      haemorrhagic infarction. Various imaging modalities for diagnosing the wandering
      spleen such as ultrasonography, CT scan, MR-angiography, nuclear scan and
      arteriography are of great value both in the asymptomatic condition and in acute
      abdomen. We report on an unusual case of wandering spleen with torsion of the
      pedicle in a middle-aged woman which we casually diagnosed intraoperatively. It
      was not possible to preserve the wandering spleen by means of splenopexy because
      the splenic infarction required a splenectomy. Though the condition was not
      diagnosed prior to surgery, prompt intervention enabled the prognosis to remain
      unvaried. We review the cases reported in the literature and discuss the
      diagnostic and therapeutic problems raised by this rare condition.

PMID- 12192944
TI  - Dimensional change of refractory materials used for ceramic veneers.
AB  - The current literature considers a number of clinical factors which affect the
      fit of all-ceramic laminate veneers. However, little consideration has been given
      to the refractory die materials, and the laboratory techniques used during the
      construction of these restorations. This study found a wide range of dimensional
      change occurred during setting and through six firing cycles, for seven
      refractories recommended for the construction of laminate veneers. It is
      therefore important that where patient treatment involves the use of veneers the
      clinician considers the suitability of the materials offered by the laboratory,
      in order to obtain the optimum marginal integrity.

PMID- 12192946
TI  - Endodontic standards in general dental practice--a survey in Birmingham, UK, Part
      2.
AB  - A postal questionnaire was used to ascertain the views of practitioners on
      postgraduate education, and on the way they performed endodontic treatment.
      Attendance at postgraduate courses was low and was influenced by the style and
      content of courses as well as financial considerations. Hands-on courses were the
      preferred mode of delivery for postgraduate education. Most practitioners wished
      to change the way they carried out their endodontic treatment, and the majority
      felt this could only occur with an increase in fees.

PMID- 12192945
TI  - Endodontic standards in general dental practice--a survey in Birmingham, Part I.
AB  - A postal questionnaire was used to evaluate endodontic treatment performed in the
      general dental services in Birmingham, assessing whether practice type--private
      or National Health Service (UK), or year of graduation, influences compliance
      with established guidelines. For the aspects of treatment investigated, many
      dentists were not following guidelines. More private practitioners adhered to the
      guidelines. Practitioner age was not related to compliance with guidelines,
      although there were differences in the procedures and materials employed among
      the different age groups. Within the survey's limits, it was concluded that
      endodontic performance varies from established guidelines.

PMID- 12192947
TI  - The effect of different polishing techniques on the surface roughness of acrylic
      resin materials.
AB  - This study evaluated three methods of surface polishing on acrylic denture base
      materials. Specimens of three commercial heat-cured acrylic resin materials were
      finished using burs, sandpaper discs and rubber wheels, and polished with
      polishing soap, paste, or by application of a UV-light-activated resin sealant.
      The resulting surface roughness was examined by scanning electron microscopy as
      well as measured by means of a stylus profile Perthometer. Surface roughness was
      reduced by polishing. Polishing paste and UV-light-activated resin sealant were
      more, and equally, effective in reducing surface roughness compared to polishing
      soap. Polishing paste or UV-light-activated resin sealant may be used to create a
      smoother surface on acrylic dentures.

PMID- 12192948
TI  - Quality of prosthetic care: patients' level of expectation, attitude and
      satisfaction.
AB  - The aim of this study was to compare pre-treatment level of expectation and
      attitude and post treatment level of satisfaction with different types of
      prosthetic treatment according to socio-economic and demographic factors. 162
      patients attending for a prosthetic rehabilitation completed an initial
      questionnaire to assess their level of expectation and attitude; after completion
      of their treatment, a second questionnaire was mailed to evaluate the level of
      satisfaction. 94 answers were returned (response rate: 62%). Results showed a
      high level of satisfaction after all prosthetic treatment, but a significant
      decrease after treatment when compared to level of expectation and attitude
      before treatment. Statistical analysis failed to show significant differences
      between prosthetic treatment, but demonstrated that the place of residence or
      level of income variable had some influence on the level of expectations and
      satisfaction. In this population, it was concluded that the pre-treatment data
      studied had limited value in predicting the outcome of the different prosthetic
      treatments performed.

PMID- 12192949
TI  - Some effects of disinfecting solutions on the properties of alginate impression
      material and dental stone.
AB  - The study investigated the effect of two disinfecting solutions on one brand of
      alginate impression material and dental stone. Control impressions were immersed
      in water for equivalent periods and the effect of storage of impressions after
      disinfection or control immersion in water was also investigated. There were no
      significant dimensional changes in impressions poured after one hour. All
      impressions stored for 16 hours before pouring showed significant dimensional
      changes. Mixing dental stone with one disinfectant caused a significant softening
      of the cast. It is strongly recommended that all impressions are thoroughly
      rinsed with water after disinfection to prevent incorporation of disinfectant in
      the cast.

PMID- 12192950
TI  - Canine risers: indications and techniques for their use.
AB  - Tooth wear leads to alterations in both static and functional occlusal contacts
      and may contribute to temporomandibular joint disorders and dysfunction.
      Treatment of tooth wear may be time consuming, expensive and destructive of
      remaining tooth tissues. Bruxism has been associated with the recording of
      abnormally high clenching forces. This paper describes a technique for the
      provision of the canine riser restoration, which deliberately alters the cuspal
      incline in canine teeth to provide a canine guided occlusion. These restorations
      may help to control excessive loading of teeth, limit further tooth wear and
      assist in the management of temporomandibular disorders and dysfunction.

PMID- 12192951
TI  - Comparative studies on the adhesion of a silicone elastomer to a chromium-cobalt
      dental alloy.
AB  - Rocatec, Kevloc and Siloc bonding systems were used to bond Molloplast-B silicone
      elastomer to a metal alloy denture base material. The mechanical strength of the
      bonds was examined using tensile tests. Two groups of tests were performed, 30
      samples after one day storage in water and 30 samples after 6 months in water at
      37 degrees C. At both testing times, the Rocatec system exhibited high
      reproducibility and the highest mean results. For the Kevloc system the values
      were lower while the Siloc system yielded the lowest values. The strength of
      samples, bonded with the Rocatec system, was improved by storage in distilled
      water at 37 degrees C.

PMID- 12192952
TI  - Long-term follow-up of implant-stabilised overdentures.
AB  - The aim of this retrospective study was to assess the long-term outcome of
      patients provided with implant-stabilised overdentures. Patients who had been
      entered into a previous trial were identified; the records were available for
      nineteen patients restored with conventional complete upper dentures and implant
      stabilised lower overdentures. The mean follow-up period was 11.5 years (range
      5.25-13.5 years). One implant was lost and all patients have successfully worn
      their prostheses, although most have experienced problems: loosening, loss and
      fracture of retaining clips, soft tissue complications and fractured bars. Nine
      patients subsequently had bars replaced with ball attachments. This conversion
      significantly reduced requirements for maintenance and professional care. Implant
      stabilised lower overdentures supported on two implants provide a simple,
      predictable solution for patients with otherwise poorly retained and unstable
      lower dentures.

PMID- 12192953
TI  - Healthy mothers, healthy babies: breastfeeding and beyond.

PMID- 12192954
TI  - HIV-positive mothers and breastfeeding.

PMID- 12192955
TI  - A case of rapid recovery of rotavirus gastro-enteritis with donor's milk.

PMID- 12192956
TI  - The association between reported childhood sexual abuse and breastfeeding
      initiation.
AB  - This study examined the association between self-identified childhood sexual
      abuse and breastfeeding initiation. A nationally representative sample of 2017
      parents with children younger than 3 years was surveyed by telephone about child
      rearing needs. Respondents were asked to report childhood sexual abuse and
      breastfeeding practices. Responses of 1220 biological mothers were analyzed. A
      possible association between self-reported childhood sexual abuse and
      breastfeeding initiation was investigated through multivariate logistic
      regression. Seven percent of the respondents reported experiencing childhood
      sexual abuse. Women who reported childhood sexual abuse were more than twice
      (adjusted odds ratio = 2.58; 95% confidence interval = 1.14, 5.85; P = .02) as
      likely to initiate breastfeeding compared with women who did not report childhood
      sexual abuse. Parenting attitudes and behaviors were compared to consider whether
      greater concern with parenting is an explanation for this association. In this
      nationally representative sample, self-identified childhood sexual abuse is
      associated with an increased likelihood of breastfeeding initiation.

PMID- 12192957
TI  - Public perceptions on breastfeeding constraints.
AB  - To describe public perceptions on breastfeeding constraints, the authors studied
      the responses of 2369 US adults who participated in the Healthstyles 2000
      national mail survey (response rate = 75%). Among them, 2351 answered at least 1
      of the 12 breastfeeding items. Public perceptions were positive for 8 of the 12
      items. Among the other 4, however, almost half of US adults (45%) agreed that a
      breastfeeding mother has to give up too many lifestyle habits, 31% thought that
      babies ought to be fed cereal or baby food by age 3 months, 31% said that 1-year
      olds should not be breastfed, and 27% considered breastfeeding in public
      embarrassing. The results revealed more negative perceptions among non-whites,
      people under 30 or above 65 years, and those who had low income and less
      education. To promote and support breastfeeding in society as a whole, these
      messages need to be considered in planning and implementing breastfeeding
      interventions.

PMID- 12192958
TI  - Increasing breastfeeding initiation and duration at a community level: an
      evaluation of Sagkeeng First Nation's community health nurse and peer counselor
      programs.
AB  - The effectiveness of two Sagkeeng First Nation breastfeeding initiatives-
      prenatal instruction by a community health nurse and a postpartum peer counselor
      (PC) program for breastfeeding women--was evaluated at a community level through
      chart audits (1992 to 1997, n = 283). Breastfeeding initiation rates increased
      from 38% in 1995 to 60% in 1997 (OR = 2.2, 95% CI 1.2-4.1, P = .01, adjusted for
      birth weight and parity). PC clients were half as likely to wean (RR = 0.5, 95%
      CI 0.25-0.98, P = .04, adjusted for birth weight and parity), with 61% still
      breastfeeding at 2 months (vs 48% nonclients) and 56% at 6 months (vs 19%). PC
      clients had fewer problems (median 1 vs 2, P = .044) and greater satisfaction
      with breastfeeding (median 5 vs 4, P = .07). Qualitative interviews (n = 22)
      confirmed PC clients as more satisfied and more confident about breastfeeding,
      with fewer problems and more information.

PMID- 12192959
TI  - Breastfeeding and employment: an assessment of employer attitudes.
AB  - Both research and anecdotal reports suggest that maternal employment is
      associated with failure to initiate breastfeeding and early breastfeeding
      attrition. The objective of this study was to describe the experience with and
      attitudes toward breastfeeding of a sample of employers in a small Midwestern
      city in the United States. Based on an analysis of 85 mail-out questionnaires, we
      found that less than half of the employers had personal experience with
      breastfeeding. A large percentage of the sample, however, indicated that they
      would be willing to facilitate women who wished to breastfeed or express milk in
      the workplace. However, these employers also stated that they saw little value to
      their business of supporting breastfeeding in the work environment. Thus,
      enhancement of breastfeeding opportunity in the work environment may come as a
      result of public and employer education but, more likely, will require some type
      of directive from official sources.

PMID- 12192960
TI  - Erythropoietin in human milk: physiology and role in infant health.
AB  - Human milk contains substantial concentrations of erythropoietin, a hormone best
      known for its role in the regulation of erythropoiesis. Recent studies show that
      erythropoietin receptors are widely distributed in human tissues, including the
      gastrointestinal tract, endothelial cells, spinal cord, and brain, suggesting
      that erythropoietin plays a wider role in infant development. Mammary epithelial
      cells contribute to the production of erythropoietin in human milk, and
      erythropoietin concentrations appear to rise slowly in human milk during the
      first few months of lactation. Current data suggest that erythropoietin in human
      milk may play a pleiomorphic role in erythropoiesis, neurodevelopment, maturation
      of the gut, apoptosis, and immunity in the infant.

PMID- 12192961
TI  - Supporting the mother coming to terms with persistent insufficient milk supply:
      the role of the lactation consultant.

PMID- 12192962
TI  - Delayed lactogenesis II secondary to gestational ovarian theca lutein cysts in
      two normal singleton pregnancies.
AB  - Hyperreactio luteinalis is an unusual condition in which, during pregnancy, both
      ovaries are enlarged by multiple theca lutein cysts that produce a high level of
      testosterone. Several weeks postpartum, the cysts resolve and testosterone level
      returns to normal. Two case studies are presented in which mothers with
      gestational ovarian theca lutein cysts experienced delayed lactogenesis II. The
      elevated testosterone at the time of birth suppressed milk production. Once the
      testosterone level dropped to approximately 300 ng/dL, milk production began.
      After the initial delay, both mothers breastfed their infants without
      supplementation.

PMID- 12192963
TI  - Statistical report of the 2001 IBLCE examination.

PMID- 12192965
TI  - Report of the International Leprosy Association Technical Foum. 25-28 February
      2002. Paris, France.

PMID- 12192964
TI  - Galactogogues: medications that induce lactation.
AB  - Galactogogues are medications that aid in initiating and maintaining adequate
      milk production. Most exert their pharmacologic effects through interactions with
      dopamine receptors, resulting in increased prolactin levels and thereby
      augmenting milk supply. Metoclopramide remains the galactogogue of choice due to
      its documented record of efficacy and safety in women and infants. Domperidone
      crosses the blood brain barrier and into the breast milk to a lesser extent than
      metoclopramide, decreasing the risk of toxicity to both mother and infant
      possibly making it an attractive alternative. Traditional antipsychotics,
      sulpiride and chlorpromazine, have been evaluated, but adverse events limit their
      use. Human growth hormone, thyrotrophin-releasing hormone, and oxytocin have also
      been studied. Finally, a natural product, fenugreek, has been purported to be
      effective in anecdotal reports. Use of this agent may be warranted after
      considering risks versus benefits.

PMID- 12192966
TI  - Integration of leprosy services.

PMID- 12192967
TI  - Leprosy control through general health services--revisiting the concept of
      integration.

PMID- 12192968
TI  - Elimination of leprosy: the integration of leprosy related activities into the
      general health services of Tamil Nadu.

PMID- 12192969
TI  - Training for integration.
AB  - Training is often suggested as the solution to the inadequacies of the health
      care system, and there is little doubt that without it, service quality would
      suffer and new techniques and technologies would be difficult to introduce;
      clearly it is an important component in any drive to achieve quality of care.
      However, in this era of cost-effectiveness and cost cutting, which is part of the
      reason for integration, it is surprising that training is often not well planned
      and is rarely evaluated in a rational manner. This paper relies on recent
      discussions within ILEP about training and the use of training materials for
      leprosy in the present environment--one in which most programmes are being
      integrated into the general health services. The development of a National
      Training Plan for Leprosy is proposed, with clear objectives, in order to best
      utilize the resources available.

PMID- 12192970
TI  - The leprosy elimination campaign in Jigawa, Nigeria: an opportunity for
      integration.
AB  - Integration of leprosy control into the general health services is regarded as an
      important condition for increasing the accessibility and sustainability of
      leprosy services. However, it is often difficult to embark on such an integration
      process. In Jigawa State in Northern Nigeria, the leprosy elimination campaign
      was used as the initiator and catalyst for the integration process. In this
      article, this challenging process is described and analysed. Available
      information is used to identify the constraints that emerged and to assess the
      consequences of integration for important aspects of leprosy control, such as
      case detection and case-holding and the accessibility and quality of the provided
      services. Some lessons from this experience are drawn that can be helpful for
      integration in other States or countries.

PMID- 12192971
TI  - Lessons in integration--operations research in an Indian leprosy NGO.
AB  - Since the Alma Ata Declaration in 1978, health systems supporting the treatment
      and control of infectious diseases like leprosy and tuberculosis have been
      encouraged to 'integrate' into the primary health care structure within
      countries. Now, more than 20 years later, countries are still grappling with the
      concept of integration and looking for ways to achieve it. This study reports
      findings from a leprosy/Tuberculosis/AIDS awareness pilot project conducted by
      LEPRA India, a leprosy non-governmental organization (NGO), between 1996 and 2000
      in Koraput district, Orissa. The project addressed the issue of integration on
      two levels. On the one hand LEPRA used the context of the project to explore ways
      in which to integrate TB services into their existing leprosy control structure.
      On the other hand, lessons from the pilot study were intended to help the
      organization find ways of linking with the government health care structure.
      Following a 'qualitative approach', this operations research project assessed the
      perceptions of communities and providers about leprosy and tuberculosis services.
      Providers across the spectrum of this plural healthcare system were asked to
      provide comment on developing stronger networks with each other, with NGOs and
      with government, while patients and communities were asked to describe the
      resources available to them and the constraints they face in accessing health
      care in general, and for leprosy and TB in particular. LEPRA staff from top
      management to the outreach workers were also approached for their views. Patients
      and communities noted that physical access to treatment was a major constraint,
      while the existence of local providers and family support structures facilitated
      health and health care. Providers expressed a willingness to collaborate (with
      LEPRA and the government), but lacked training, adequate staff support and the
      appropriate equipment/technical resources. Also lacking were adequate information
      campaigns to inform the public about these diseases and their treatment. This
      information has provided LEPRA with an understanding of how they might best fill
      gaps in the existing system and therefore assist in the process of integrating
      services in their own organization and through the primary health care structure.
      To achieve this aim, LEPRA will increasingly become involved in developing
      relationships and partnerships with government in the delivery of training and
      services and in infrastructure development.

PMID- 12192972
TI  - NGO and state: co-operation between a leprosy relief association and other
      institutions in South America.
AB  - In a structured questionnaire format, the German Leprosy Relief Association
      (GLRA) interviewed its representatives in two Federal states of Brazil and four
      other Latin American countries about the distribution, between itself, the state
      and other institutions of a) responsibility for funding and b) implementation of
      activities, in relation to leprosy control. Wherever the political commitment was
      given, GLRA's role could be reduced to the highly effective support of the
      government structure in well-defined areas, most particularly in staff training,
      health education and eventually in programme supervision. This public-private
      partnership under the umbrella of the host government sustains a small, but
      important specialized leprosy component whilst routine services are well
      integrated into the general health system.

PMID- 12192973
TI  - Initial experiences of implementation of functional integration (FI) in LEPRA
      India projects in Orissa.
AB  - In 2000, the Government of the State of Orissa (population 37 million) in India
      decided to introduce functional integration for the control of leprosy, in place
      of the long-established vertical programme, using the general health services and
      the primary health care system. This paper describes the initial (9 months)
      experience of implementing this strategy in two projects run by LEPRA India. One
      of these, in the district of Koraput, was established in 1991 and covers a
      population of 1.5 million people. The other, in Kalahandi district, started in
      1997 and covers a population of 600,000. Both projects operate under difficult
      conditions with regard to terrain, the use of numerous tribal languages,
      illiteracy, water shortage, poor roads and communications. The preparatory phase
      included intensive health education of the public on leprosy, using a wide range
      of educational media and techniques. At the same time, LEPRA India supported the
      Government in the training and orientation of trainers, medical officers, primary
      health care staff and female health workers at village level. In all, over 2000
      were trained. This paper describes all aspects of the implementation of
      functional integration in these two areas. In the 9-month period, 4207 suspect
      cases were referred to medical officers by health workers, but only 256 (6%) were
      confirmed as having leprosy. There were 169 confirmed self-reporting cases.
      Despite the clearly understood intention to involve primary health staff in case
      detection, 67% of all cases were in fact detected by LEPRA India, possibly due to
      overlapping attendance at clinics by vertical and general staff. There is
      obviously a need for further training of the general staff since only 6% of cases
      referred by them were confirmed as having leprosy. Steps must also be taken to
      ensure that the emphasis on case detection, confirmation and treatment shifts
      from the vertical to the general health staff. The supply of anti-leprosy drugs
      and steroids to primary health centers needs improvement. Appropriate teaching
      and learning material is urgently needed for both field staff and medical
      officers.

PMID- 12192974
TI  - Processes and challenges: how the Sri Lankan health system managed the
      integration of leprosy services.
AB  - At the end of 1999, the Ministry of Health in Sri Lanka took the bold decision to
      integrate its Leprosy Services within the country's general health system. The
      integration was completed in February 2001 and is already starting to bear fruit,
      but implementing the necessary changes has been a challenging task. Many new
      procedures had to be established, logistics improved, attitudes changed and
      health workers trained. A broad bridge between curative and preventative health
      services needed to be built. Integration efforts were supported by an advertising
      campaign to inform people that leprosy, like any other illness, can be treated at
      all health facilities. Contrary to the expectation that quality of service would
      drop following integration, more cases are now detected and an extensive network
      of government doctors is able to diagnose, treat and manage leprosy patients more
      efficiently. Prevalence has increased by 36% and the new case load by 41%. A few
      areas still need more attention, such as integrating MDT supplies within existing
      systems and improving the flow of information, but nonetheless the ownership of
      leprosy is shifting rapidly to local health services.

PMID- 12192975
TI  - Social stigma: a comparative qualitative study of integrated and vertical care
      approaches to leprosy.
AB  - Integration of leprosy into the general health system is very much emphasized by
      health care planners. One prime reason stated for this is to reduce stigma
      attached to this disease. This study was conducted in the state of Maharashtra,
      India, to compare the level of social stigma towards leprosy in communities with
      a vertical and an integrated programme. The data were collected in three areas of
      five villages each. The first two areas were in an integrated programme to test
      for internal consistency and the third in a vertical programme. All the leprosy
      patients with visible deformities in these villages were enrolled in the study,
      and an in-depth stigma measurement scale was administered. In addition, focus
      group discussions were conducted among the family members of leprosy patients and
      participative rural appraisal was done in the communities. The data were analysed
      using qualitative methods. A total of 24 leprosy patients with visible
      deformities participated in the in-depth stigma measurement exercise from 15
      villages. Fifteen focus group discussions were conducted with families of leprosy
      patients and an equal number of participatory rural appraisals with communities
      were done. The results show that social stigma was virtually non-existent among
      the communities with the integrated approach and minimally experienced by leprosy
      patients in this model. However, a high level of self-stigmatization among
      leprosy patients was observed in the vertical approach and equally a high level
      of social stigma was found in their communities, which led to reduced interaction
      between the leprosy patients and their communities. The integrated approach to
      community-based primary health care is effective in reducing leprosy stigma in
      society.

PMID- 12192976
TI  - Clinical features of HIV disease in developing countries.
AB  - HIV disease progresses from an asymptomatic period of variable duration, through
      mild symptoms, to severe disease characteristic of cellular immunodeficiency. The
      rate of progression from infection to severe disease is probably similar world
      wide. However, individuals in developing countries have more symptomatic disease,
      in keeping with the high incidence of morbidity in the general population, and
      poor survival with advanced disease. The clinical manifestations of severe HIV
      related immunosuppression vary with geographical region. Tuberculosis (TB) is the
      most important severe opportunistic disease in developing countries: the clinical
      presentation may differ from TB in the immunocompetent. Bacterial infections,
      particularly due to Streptococcus pneumoniae and non-typhoid Salmonella spp., are
      also important causes of morbidity and mortality. Fungal diseases such as
      Pneumocystis carinii pneumonia (PCP), cryptococcosis, histoplasmosis and
      penicilliosis vary in prevalence in different geographical regions. A high index
      of suspicion of HIV infection and knowledge of the local spectrum of HIV disease
      are important for early diagnosis and appropriate management of HIV-related
      disease.

PMID- 12192977
TI  - [Use of GIS-technologies in management of troop medical support].

PMID- 12192978
TI  - [Development of automated work places for medical service headquarters].

PMID- 12192979
TI  - [An automated information system for the wounded and patients in a military
      hospital].

PMID- 12192980
TI  - [An improved system for youth enrollment at physician education departments at
      the Military Medical Academy].

PMID- 12192981
TI  - [The work experience of the Disaster Medical Services of Ministry of Health of
      Russia in the clean-up of medical and sanitary aftermath of flood in Lensk].

PMID- 12192982
TI  - [Suicidal behavior of the contract servicemen].
AB  - The authors analyze the suicidologic situation, the level of suicides and
      parasuicides in society, Armed Forces and among the contract servicemen
      personally. The suicidologic data are evaluated, and reasons, risk factors,
      peculiarities of postsuicidal period of contract servicemen are defined.

PMID- 12192983
TI  - [Possibilities of prenosologic diagnosis of cardiovascular diseases in men called
      up for military service].
AB  - The investigation of functional state of cardiovascular system and whole body was
      conducted in the draftees aged 18-19. Wide spread of pre-nosologic states was
      revealed that manifested by different disorders but cardiovascular pathology
      prevailed. However at the moment of investigation these disorders were not
      nosospecific but showed the presence of strain in the system of body adaptive
      regulation. The results obtained and information model of adaptive regulation
      system allowed to determine the most informative and available for military
      medical commission diagnostic criteria of pre-pathologic states. It will
      facilitate the appropriate selection of draftees.

PMID- 12192984
TI  - [Medical care for the burnt in modern local military conflicts].
AB  - The article is devoted to the experience of treatment of the servicemen who
      burned during the hostilities in Afghanistan (1979-1989), Tadjikistan (1992-1994)
      and in Republic of Chechnya (1994-2996). Medical care rendered in 18,921 cases of
      burns and combined trauma (the burn prevailed) is analyzed: 1201--in Afghanistan,
      205--in Tadjikistan and 415--in Republic of Chechnya. In the structure of
      sanitary losses of surgical character the burned persons constituted 2.5% in
      Afghanistan, 7.0%--in Tadjikistan and 3.9%--in Republic of Chechnya. The most
      effective was the medical-evacuation system in Afghanistan. The optimal medical
      evacuation system during the local armed conflicts and wars is the evacuation
      consisted of two stages: first medical aid--specialized medical care.

PMID- 12192985
TI  - [The state and perspectives of medical support for Armed forces of Russian
      Federation].
AB  - Critical analysis of the state of medical support of military district and navy
      staff allowed the specialists from Military Medical Headquarters to reveal 6 main
      problems of military medicine and to determine the ways of their solution. The
      models of territorial military medical infrastructure taking into account the
      prognosis of possible development of local wars and armed conflicts are worked
      out. The attempts to form the face of field hospital of the future became more
      effective. Constant attention is given to development of army and front complexes
      of medical service that could be used in conditions of regional (large-scale)
      war. The hospital bases continue to reduce and transfer to the new organizational
      structure. Owing to it part of the resources becomes free and is used for
      improvement of battle readiness of new units. The new time of effective planning
      and complex development based on introduction into the practice of the new forms
      and methods of control has come.

PMID- 12192986
TI  - [Rhinoseptoplasty in a garrison hospital].

PMID- 12192987
TI  - [Correction of affective disorders in patients with alcohol dependence].

PMID- 12192988
TI  - [The cardiac pump function in adolescents with scoliosis].

PMID- 12192990
TI  - [The relationship between tuberculosis incidence in Russian population and
      servicemen].

PMID- 12192989
TI  - [Rispolept (risperidone) efficacy in the treatment of patients with schizophrenia
      and psychoactive drug dependence].

PMID- 12192991
TI  - [Effect of cosmoheliophysical factors on the psychic state of patients with drug
      dependence].

PMID- 12192992
TI  - [Diagnosis of value and motivation components as a way to decreasing neurotic and
      psychosomatic morbidity in servicemen].

PMID- 12192993
TI  - [Etiology of barodentalgia in flying personnel].

PMID- 12192994
TI  - [Technical esthetics in design of mobile surgical units].

PMID- 12192995
TI  - [Medical care for prisoners of war and displaced persons at the end of the World
      War II].

PMID- 12192996
TI  - [Reforms in medical education in the first half of the XIX century in Russia].

PMID- 12192997
TI  - The Mamiya Medical Heritage Center: a treasure of Hawaii medical history in the
      Hawaii Medical Library.

PMID- 12192998
TI  - Antibiotic treatment of urinary tract infections at a skilled nursing facility in
      Hawaii.

PMID- 12192999
TI  - Hawaii's Neuromuscular Disease Biopsy Registry. A quarter-century compilation of
      muscle biopsy diagnoses in Hawaii.
AB  - INTRODUCTION: The Department of Pathology at Straub Clinic & Hospital began using
      enzyme histochemical techniques to examine muscle biopsies in 1976 and has
      processed most of the muscle biopsies performed in Hawaii for the past 25 years.
      A Muscle Biopsy Registry of biopsy findings was established in 1992 and
      information concerning 1,230 biopsies during the period December 1976 to June,
      2000 entered into the Registry's data base. The goal was to document data derived
      from biopsy-based diagnoses of neuromuscular diseases since none currently
      exists. METHODS: Muscle biopsies received in a fresh state in the Straub
      Pathology Department were processed utilizing a modern approach incorporating
      routine histological and enzyme histochemical staining techniques of frozen
      sections. One pathologist [LJL] documented findings and established diagnoses for
      all cases. Patient information, demographics and diagnoses were recorded
      utilizing a Microsoft Excel spreadsheet program. RESULTS: Data sorts conducted
      from the Registry's data base of 1,230 biopsies produced graphs and tables
      illustrating demographic statistics regarding diagnoses and findings in 1,044
      different patients some of whom had multiple biopsies. CONCLUSIONS: Hawaii's
      Neuromuscular Disease Biopsy Registry constitutes a compilation of a quarter
      century of muscle biopsy-based diagnoses utilizing enzyme histochemical
      diagnostic techniques in pediatric and adult age groups, including specific
      diagnoses encountered in different ethnic groups. This information constitutes a
      benchmark for future epidemiologic studies, and a basis for comparison with data
      derived from clinical diagnoses and data derived from Death Certificates.

PMID- 12193000
TI  - Medical technology at the John A. Burns School of Medicine.

PMID- 12193001
TI  - Hawaii Society of Clinical Oncology.

PMID- 12193002
TI  - Domestic violence.... Is not just a family problem.... It's a crime!

PMID- 12193003
TI  - Spiritual healing and the appliance of science.

PMID- 12193004
TI  - Haemoglobin level in Scottish intensive care patients--a national one day survey.
AB  - Objectives were to determine haemoglobin (Hb) levels present in patients and
      blood ordering habits of clinicians within Scottish Intensive Care Units (ICUs)
      on one typical day. A questionnaire survey (February 29 2000) was sent to all
      adult Scottish ICUs. All patients present in the responding adult ICUs in
      Scotland on the above date were included. MEASUREMENTS AND MAIN RESULTS: Nineteen
      (73%) of the 26 Scottish Adult Intensive Care Units (ICUs) responded to the
      questionnaire. Data were received from 78 patients, 8 (10%) received blood. Mean
      initial Hb was 102 g/l (range 63-138). Modal transfusion trigger haemoglobin was
      80 g/l in 38% of subjects at first trigger, 100 g/l in 24% of cases. No intensive
      care unit allowed haemoglobin to fall below 70 g/l and no patients were
      transfused when measured Hb was greater than 100 g/l. The presence of ischaemic
      heart disease was the second most important trigger to transfuse after
      haemoglobin level. Modal transfusion was 2 units (n = 7). Only one patient
      received a single unit transfusion. CONCLUSIONS: Scottish ICUs maintain Hb
      between 70 and 100 g/l but clinicians are currently not consistent when ordering
      blood. More investigation is required to determine the optimal haemoglobin in our
      ICU population.

PMID- 12193005
TI  - Thrombolysis and its implications in the management of stroke in the accident and
      emergency department.
AB  - OBJECTIVES: Examination of initial management of stroke patients in the emergency
      setting to assess feasibility of thrombolysis for acute ischaemic stroke.
      METHODS: Retrospective analysis of all patients presenting with a clinical
      diagnosis of stroke over a two month period. Exclusion criteria for thrombolysis
      were applied to assess the number of patients that would potentially have been
      eligible for thrombolysis. RESULTS: Of 94 patients identified with clinical
      stroke, only 57 (60.6%) had a CT scan; 23 (24.4%) were confirmed as having had an
      acute ischaemic stroke. Mean delay in scanning was 2.2 days (range 0-15 days).
      Even if all patients had presented and been scanned within three hours (as
      required for thrombolysis), only six (6.4%) patients would have been eligible for
      thrombolysis. CONCLUSIONS: The great majority of patients presenting with
      clinical stroke do not fulfill the criteria for thrombolysis. Current practice
      involves significant delays in CT scanning, which has implications for resource
      structuring should thrombolysis become widely available.

PMID- 12193006
TI  - Do junior house officers routinely test visual acuity and perform ophthalmoscopy?
AB  - Our objective was to assess junior house officer (JHO) practice of visual acuity
      testing and ophthalmoscopy in clerking patients. DESIGN: Cross-sectional
      questionnaire-based study using a standardised structured interview technique.
      SETTING: A Scottish university teaching hospital employing 65 JHOs. PARTICIPANTS:
      All medical and surgical JHOs from this hospital were interviewed over a three
      month period. MAIN OUTCOME MEASURES: Questionnaire-based data on the subjective
      responses studying current practice of visual acuity testing, and direct
      ophthalmoscopy with and without topical mydriatics. RESULTS: 18.5% and 4.6% of
      participants perform daily ophthalmoscopy and visual acuity testing respectively.
      Most do not routinely use the Snellen chart (80.0%) or topical mydriatics during
      ophthalmoscopy (75.4%). JHOs claimed these were not easily available in the
      wards. CONCLUSIONS: The majority of JHOs fail to test visual acuity or perform
      ophthalmoscopy in clerking patients. This study highlights the poor availability
      of Snellen charts, functioning ophthalmoscopes, and topical mydriatics in the
      wards. This warrants further investigation.

PMID- 12193007
TI  - Hypertrophic cardiomyopathy with shared morphology in identical twins: a case
      report.
AB  - We report the case of identical twin sisters, both with hypertrophic
      cardiomyopathy, and both found to have similar echocardiographic appearances in
      the form of asymmetric septal hypertrophy. This is unusual, in that published
      reports commonly describe the heterogeneous expression of this condition in
      twins.

PMID- 12193008
TI  - Not modern-day body-snatching: the response of the public.
AB  - At recent presentations on the history of anatomy in the West of Scotland, our
      group has been asked whether we would regard the revelations of 1999-2001 about
      organ retention as a modern form of body-snatching. We have compared newspaper
      reports of the Glasgow Herald from 1823 to 1832, the decade prior to the Anatomy
      Act of 1832, and the Herald, Sunday Herald and Evening Times from 1999 to 2001.
      Clearly body-snatchers appropriated whole corpses while the recent troubles
      concerned individual organs. Body-snatching was illegal while the crisis over
      organ retention arose from differing expectations between the medical profession
      and the public. Both practices caused huge public concern and distress to
      relatives. There are, however, interesting differences between the two sets of
      reports. The public had been aware of body-snatching for many years prior to the
      Anatomy Act, which regulated the supply of cadavers, whereas revelations about
      organ retention came as a shock. In the organ retention crisis, the parents of
      the children were more organised in supporting each other and in campaigning for
      change than were the public in the days of the resurrectionists.

PMID- 12193009
TI  - Durhamycin A, a potent inhibitor of HIV Tat transactivation.
AB  - Tat is a small HIV protein essential for both viral replication and the
      progression of HIV disease. In our efforts to discover Tat inhibitors from
      natural product screening of microbial fermentation extracts, we discovered
      durhamycin A (1) as a potent inhibitor (IC(50) = 4.8 nM) of Tat transactivation.
      Detailed NMR and MS/MS studies were utilized to elucidate the structure of 1 as a
      new member of the aureolic acid family of antibiotics. It consists of
      tetrasaccharide and disaccharide moieties attached to the aglycone, which is
      hitherto unknown in the aureolic acid family. Three other novel analogues,
      durhamycin B (2), compound (3), and the aglycone (4), were also discovered or
      chemically prepared that were less potent than durhamycin A.

PMID- 12193010
TI  - Ancistrocongolines A-D, new naphthylisoquinoline alkaloids from ancistrocladus
      congolensis.
AB  - Four new naphthylisoquinoline alkaloids, ancistrocongolines A-D (4-7) were
      isolated from Ancistrocladus congolensis, along with the known compound
      korupensamine A (8). Structural elucidation was achieved by chemical,
      spectroscopic, and chiroptical methods. Their biological activities against the
      pathogens of malaria, Leishmaniasis, Chagas disease, and African sleeping
      sickness were evaluated.

PMID- 12193011
TI  - Five new labdane diterpenes from Aster oharai.
AB  - Five new labdane diterpenes (1-5) together with seven known diterpenes have been
      isolated from a methanol extract of the aerial parts of Aster oharai. Five new
      structures were determined as 7alpha-hydroperoxylabda-8(17),14-dien-13(R)-ol-4-O
      acetyl-alpha-L-6-deoxyidopyranoside (1), 7alpha-hydroperoxylabda-8,14-dien-13(R)
      ol-4-O-acetyl-alpha-L-6-deoxyidopyranoside (2), labda-7,14-dien-13(R)-ol-4-O
      acetyl-alpha-L-rhamnopyranoside (3), labda-7,14-dien-13(R)-ol-3-O-acetyl-alpha-L
      rhamnopyranoside (4), and labda-7,14-dien-13(R)-ol-2-O-acetyl-alpha-L
      rhamnopyranoside (5), on the basis of spectroscopic methods. Compound 1 showed
      moderate cytotoxicity against four cultured human tumor cell lines with ED(50)
      values ranging from 1.1 to 7.7 microg/mL.

PMID- 12193012
TI  - New furanoid diterpenes from Caesalpinia pulcherrima.
AB  - Four new cassane-type furanoditerpenoids (1-4) were isolated from the air-dried
      leaves of Caesalpinia pulcherrima. Their structures were elucidated by spectral
      data interpretation. The exocyclic methylene compound 1 readily isomerized and
      oxidized to the benzofuran 4. Benzyl 2,6-dimethoxybenzoate (5) was also
      identified in this study. Antimicrobial tests on 1-5 indicated that they were
      active against several bacteria (S. aureus, E. coli, P. aeruginosa, and B.
      subtilis) and fungi (C. albicans and T. mentagrophytes).

PMID- 12193013
TI  - Diterpenoids from Isodon adenantha.
AB  - Eleven new diterpenoids, adenanthins B-L (1-11), together with five known
      analogues, calcicolin B (12), adenanthin (13), weisiensin A (14), nervosanin
      (15), and forrestin C (16), were isolated from the aerial parts of Isodon
      adenantha. The structures of 1-11 were elucidated on the basis of spectral
      methods, as well as the X-ray crystallographic analysis of 11. Compounds 2, 5,
      and 14 showed significant inhibitory activities against K562 cells, with IC(50)
      values less than 4.0 microg/mL, respectively.

PMID- 12193014
TI  - Gaboroquinones A and B and 4'-O-demethylknipholone-4'-O-beta-D-glucopyranoside,
      phenylanthraquinones from the roots of Bulbine frutescens.
AB  - The novel phenylanthraquinones 4'-O-demethylknipholone-4'-O-beta-D
      glucopyranoside (2) and gaboroquinones A (3) and B (4) were isolated from the
      African medicinal plant Bulbine frutescens. Biaryl 2 represents the first
      phenylanthraquinone glucoside, while 3 and 4 are the first side-chain
      hydroxylated phenylanthraquinones. Their constitutions were determined by
      spectroscopic analysis, in particular by HMBC, HMQC, and ROESY NMR
      investigations, and by chemical transformations. The axial configurations were
      elucidated chemically, by deglucosylation of 2 and by side-chain deoxygenation of
      3 and 4 to give the known phenylanthraquinones 4'-O-demethylknipholone (5),
      isoknipholone (6), and knipholone (1), respectively, and chiroptically, by CD
      investigations. Compounds 2, 3, and 4 showed moderate to good antiplasmodial and
      antitrypanosomal activities in vitro.

PMID- 12193015
TI  - Phenylphenalenone-related compounds: chemotaxonomic markers of the haemodoraceae
      from Xiphidium caeruleum.
AB  - Phytochemical analysis of Xiphidium caeruleum, a neotropical member of the family
      Haemodoraceae, resulted in the isolation and identification of a variety of
      phenylphenalenone-related compounds. The structures of four new
      phenylbenzoisochromenones (3, 6, 7, 10), a new phenylbenzoisoquinolinone (4), and
      two new oxabenzochrysenones (11, 12) were elucidated using MS and NMR
      spectroscopic techniques. In addition, five new glucosides (14-18) were
      identified, among them four allophanyl glucosides (15-18), representing a novel
      type of 6'-substituted glucosidic natural product. On the basis of the common
      occurrence of these 12 new and four known structures (2, 5, 9, 13), hypothetical
      biosynthetic relationships are discussed. The natural product distribution of
      other genera of the Haemodoraceae is used as the basis to elaborate biogeographic
      characteristics of this plant family.

PMID- 12193017
TI  - Design and synthesis of a combinatorial chemistry library of 7-acyl, 10-acyl, and
      7,10-diacyl analogues of paclitaxel (taxol) using solid phase synthesis.
AB  - A series of 10-acyl and 7,10-diacyl paclitaxel analogues (7a-7e and 9a-9u) have
      been synthesized using a solid phase combinatorial chemistry approach, and a
      second series of 7-acyl-10-deacetylpaclitaxel analogues have been prepared by
      conventional chemistry. In the first series, 10-deacetylpaclitaxel (4) was linked
      through its 2'-hydroxyl group using 1% polystyrene-divinyl benzene resin
      functionalized with butyldiethylsilane linker (PS-DES) and then acylated at the C
      10 hydroxyl group with various anhydrides and dialkyl dicarbonates in the
      presence of CeCl(3). The resin-bound C-10 acylated paclitaxel derivatives (6a-6e)
      were then treated with various carboxylic acids in the presence of 1,3
      diisopropylcarbodiimide in toluene to provide polymer-supported 7,10
      diacylpaclitaxels (8a-8u). These 7-acyl- and 7,10-diacylpaclitaxels (6a-6e and 8a
      8u) were cleaved from the resin to give the 24 paclitaxel analogues 7a-7e and 9a
      9u. Nine 7-acyl-10-deacetylpaclitaxel analogues were also prepared by
      conventional chemistry. Methodology to determine the tubulin-assembly activity of
      compounds prepared in small quantities by a combinatorial approach has been
      developed, and four analogues with improved tubulin-assembly activity as compared
      with paclitaxel were found, together with two analogues with improved
      cytotoxicity.

PMID- 12193016
TI  - Kinetic study of littorine rearrangement in Datura innoxia hairy roots by (13)C
      NMR spectroscopy.
AB  - The kinetics of tropane alkaloid biosynthesis, particularly the isomerization of
      littorine into hyoscyamine, were studied by analyzing the kinetics of carbon-13
      ((13)C) in metabolites of Datura innoxia hairy root cultures fed with labeled
      tropoyl moiety precursors. Both littorine and hyoscyamine were the major
      alkaloids accumulated, while scopolamine was never detected. Feeding root
      cultures with (RS)-phenyl[1,3-(13)C(2)]lactic acid led to (13)C spin-spin
      coupling detected on C-1' and C-2' of the hyoscyamine skeleton, which validated
      the intramolecular rearrangement of littorine into hyoscyamine. Label from
      phenyl[1-(13)C]alanine or (RS)-phenyl[1,3-(13)C(2)]lactic acid was incorporated
      at higher levels in littorine than in hyoscyamine. Initially, the apparent
      hyoscyamine biosynthesized rate (v(app)()hyo = 0.9 micromol (13)C.flask(-1).d(
      1)) was lower than littorine formation (v(app)()litto = 1.8 micromol (13)C.flask(
      1).d(-1)), suggesting that the isomerization reaction could be rate limiting. The
      results obtained for the kinetics of littorine biosynthesis were in agreement
      with the role of this compound as a direct precursor of hyoscyamine biosynthesis.

PMID- 12193018
TI  - Characterization of a fucoarabinogalactan, the main polysaccharide from the gum
      exudate of Croton urucurana.
AB  - A fucoarabinogalactan (CU-1), the main component of the gum exudate of the
      medicinal plant Croton urucurana, has been isolated by precipitation and
      subsequent dialysis and finally purified by ion-exchange chromatography. The
      estimated average molecular weight of CU-1 by gel permeation chromatography was
      approximately 2.48 x 10(6) Da. CU-1 was found to contain 1.0% proteins and 93.7%
      total sugars, mainly fucose, arabinose, and galactose (molar ratio: 7.8, 8.1,
      19.0), and minor quantities of mannose, xylose, glucose, and uronic acids (molar
      ratio: 2.2, 1.0, 0.3, 3.0). Among the uronic acids, glucuronic acid was
      identified and the presence of mannuronic acid could be also presumed.
      Methylation analysis of this polysaccharide revealed high proportions of 1,3
      linked, 1,2,3-linked, and 1,2,3,6-linked galactose, 1-linked fucose, and 1-linked
      arabinose. This suggests that CU-1 is constituted by a principal skeleton of (1-
      >3)-linked galactopyranose units, with some of these galactose units branched at
      the 2-position or at both the 2- and 6-positions, and with mainly terminal
      fucopyranosyl and arabinofuranosyl residues in the side chains. This is the first
      report on the polysaccharide constitution of a gum exudate from a Croton species.

PMID- 12193019
TI  - Naturally occurring cembranes from an Australian sarcophyton species.
AB  - Naturally occurring cembranes 1-4 have been isolated from a Sarcophyton sp. These
      compounds have not previously been found to occur in nature but had been obtained
      as intermediates in a synthetic modification from tobacco. The absolute
      stereochemistries of 3 and 4 were determined. Compounds 1 and 2 inhibited the
      binding of [(3)H]8-cyclopentyl-1,3-dipropylxanthine to rat-brain adenosine A(1)
      receptors.

PMID- 12193020
TI  - New flavonol oligoglycosides and polyacylated sucroses with inhibitory effects on
      aldose reductase and platelet aggregation from the flowers of Prunus mume.
AB  - The methanolic extract from the fresh flowers of Prunus mume exhibited inhibitory
      effects against aldose reductase and platelet aggregation. From the methanolic
      extract, two new flavonol oligoglycosides, 2' '-O-acetylrutin and 2' '-O-acetyl
      3'-O-methylrutin, and two new polyacylated sucroses, prunoses I and II, were
      isolated together with 11 known constituents. The structures of 2' '-O
      acetylrutin, 2' '-O-acetyl-3'-O-methylrutin, and prunoses I and II were
      determined on the basis of chemical and physicochemical evidence as quercetin 3-O
      alpha-L-rhamnopyranosyl(1-->6)-2' '-O-acetyl-beta-D-glucopyranoside, 3'-O
      methylquercetin 3-O-alpha-L-rhamnopyranosyl(1-->6)-2' '-O-acetyl-beta-D
      glucopyranoside, 1,4,3',4',6'-penta-O-acetyl-6-O-p-coumaroylsucrose, and
      1,3',4',6'-tetra-O-acetyl-6-O-p-coumaroylsucrose, respectively. The flavonol
      glycosides and prunose I were found to inhibit aldose reductase, while prunoses I
      and II inhibited platelet aggregation induced by thrombin.

PMID- 12193021
TI  - Identification and electrophysiological activity of a novel hydroxy ketone
      emitted by male cereal leaf beetles.
AB  - Comparisons of collections of volatiles from male and female Oulema melanopus,
      feeding on host foliage (oats), revealed an electrophysiologically active male
      specific compound, (E)-8-hydroxy-6-methyl-6-octen-3-one (7), which is a new
      natural product. The structure of 7 was elucidated by spectroscopic and
      microchemical studies and confirmed by chemical synthesis. Antennal
      electrophysiology showed the sensitive detection of 7 by both sexes, which is
      consistent with a male-produced aggregation pheromone.

PMID- 12193022
TI  - Novel cytotoxic oxygenated C29 sterols from the Colombian marine sponge
      Polymastia tenax.
AB  - Three new sterols, 5alpha,6alpha-epoxy-24R-ethylcholest-8(14)-en-3beta,7alpha
      diol (1), 5alpha,6alpha-epoxy-24R-ethylcholest-8-en-3beta,7alpha-diol (2), and
      3beta-hydroxy-24R-ethylcholesta-5,8-dien-7-one (3), have been isolated from the
      marine sponge Polymastia tenax, collected in the Colombian Caribbean, and their
      structures established on the basis of extensive NMR and MS studies. Compounds 1
      and 2 showed antiproliferative activity toward A-549, HT-29, H-116, MS-1, and PC
      3 tumor cells in the range 0.5-10 microg/mL.

PMID- 12193023
TI  - Four new compounds from the seeds of Cassia fistula.
AB  - Four new compounds, 5-(2-hydroxyphenoxymethyl)furfural (1), (2'S)-7-hydroxy-5-
      hydroxymethyl-2-(2'-hydroxypropyl)chromone (2), benzyl 2-hydroxy-3,6
      dimethoxybenzoate (3), and benzyl 2beta-O-D-glucopyranosyl-3,6-dimethoxybenzoate
      (4), together with four known compounds, 5-hydroxymethylfurfural, (2'S)-7-hydroxy
      2-(2'-hydroxypropyl)-5-methylchromone, and two oxyanthraquinones, chrysophanol
      and chrysophanein, were isolated and identified from the seeds of Cassia fistula.
      The structures of 1-4 were determined on the basis of spectral data explanation,
      and the synthesis of compound 1 was carried out.

PMID- 12193024
TI  - Swinhoeiamide A, a new highly active calyculin derivative from the marine sponge
      Theonella swinhoei.
AB  - Analysis of the Papua New Guinean sponge Theonella swinhoei afforded a new
      calyculinamide-related congener for which we propose the name swinhoeiamide A
      (1). The structure of the new compound was unambiguously established on the basis
      of NMR spectroscopic ((1)H, (13)C, COSY, HMBC) and mass spectrometric (FABMS)
      data. Swinhoeiamide A exhibited insecticidal activity toward neonate larvae of
      the polyphagous pest insect Spodoptera littoralis when incorporated in an
      artificial diet offered to the larvae in a chronic feeding bioassay (ED(50) 2.11
      ppm, LD(50) 2.98 ppm). Furthermore, it was found to be fungicidal against Candida
      albicans and Aspergillus fumigatus (MIC 1.2 and 1.0 microg/mL, respectively).

PMID- 12193025
TI  - 5-hydroxytryptamine-derived alkaloids from two marine sponges of the genus
      Hyrtios.
AB  - Indonesian specimens of the marine sponges Hyrtios erectus and H. reticulatus
      were found to contain 5-hydroxytryptamine-derived alkaloids. Their structures
      were determined on the basis of their spectral properties. H. erectus contained
      hyrtiosulawesine (4), a new beta-carboline alkaloid, together with the already
      known alkaloids 5-hydroxyindole-3-carbaldehyde (1), hyrtiosin B (2), and 5
      hydroxy-3-(2-hydroxyethyl)indole (3). H. reticulatus contained the novel
      derivative 1,6-dihydroxy-1,2,3,4-tetrahydro-beta-carboline (11) together with
      serotonin (5), 6-hydroxy-1-methyl-1,2,3,4-tetrahydro-beta-carboline (7), and 6
      hydroxy-3,4-dihydro-1-oxo-beta-carboline (9).

PMID- 12193026
TI  - Three new tetranortriterpenoids from neem seed oil.
AB  - Three new tetranortriterpenoids, 1alpha,2alpha-epoxy-17beta-hydroxyazadiradione
      (1), 1alpha,2alpha-epoxynimolicinol (2), and 7-deacetylnimolicinol (3), have been
      isolated from a methanol extract of neem oil (Azadirachta indica, seed oil) along
      with the known compounds epoxyazadiradione, 17beta-hydroxyazadiradione, gedunin,
      nimbin, and nimolicinol (4). Spectral studies and chemical transformations were
      used to establish the structure of compounds 1-3. The characterization of the
      epoxides 1 and 2 in neem oil is of biogenetic significance, as they may be
      considered as intermediates between A-ring enones and 1,3-diols among the A.
      indica tetranortriterpenoids.

PMID- 12193027
TI  - Neoclerodane diterpenoids from Croton eluteria.
AB  - Five new neoclerodane diterpenoids, rel-(3R,4S,5R,7R,8S,9R,10S,12R,20S)-7-acetoxy
      15,16,12,20-diepoxy-3,4-dihydroxy-20-methoxyneocleroda-13(16),14-diene (1), rel
      (3R,4S,5R,7R,8S,9R,10S,12R,20S)-7-acetoxy-15,16,12,20-diepoxy-3,4,20
      trihydroxyneocleroda-13(16),14-diene (2), rel-(3R,4S,5S,6R,7S,8S, 9R,10S,12R,20S)
      6,7-diacetoxy-3,4,15,16,12,20-triepoxy-20-hydroxyneocleroda-13(16),14-diene (3),
      rel-(3R,4S,5R,7R,8S,9R,10S,12R,20S)-7-acetoxy-3,4,15,16,12,20-triepoxy-20
      hydroxyneocleroda-13(16),14-diene (4), and rel-(3R,4S,5R,7R,8S,9R,10S,12R,20R)
      7,20-diacetoxy-3,4,15,16,12,20-triepoxyneocleroda-13(16),14-diene (5), have been
      isolated from the bark of Croton eluteria. The structures of the compounds 1-5
      (cascarillins E-I) were determined by spectroscopic data interpretation.

PMID- 12193028
TI  - Employing dereplication and gradient 1D NMR methods to rapidly characterize
      sponge-derived sesterterpenes.
AB  - The sesterterpene constituents of two Indo-Pacific sponges were investigated and
      rapidly characterized using aggressive dereplication methods along with gradient
      1D NMR techniques. Lendenfeldia frondosa yielded three sesterterpenes:
      12beta,16beta,22-trihydroxy-24alpha-methylscalar-25beta,24alpha-olide (1), the 24
      epimer of a known compound; 12beta,22-dihydroxy-24-methylscalar-17-en-24,25-olide
      (2), a known compound; and 22-hydroxy-24-methylsedn-16-en-24-one-12beta,25beta
      olide (3), a new compound. A Hyrtios sp. sponge yielded known 12alpha-acetoxy
      16beta-hydroxyscalarolbutenolide (5).

PMID- 12193029
TI  - Schizopeptin 791, a new anabeanopeptin-like cyclic peptide from the
      cyanobacterium Schizothrix sp.
AB  - Schizopeptin 791 (1), a new trypsin inhibitor, related in structure to the
      anabeanopeptins, was isolated from the hydrophilic extract of the cultured
      terrestrial cyanobacterium Schizothrix sp. Homo- and heteronuclear 2D NMR
      techniques as well as HRFABMS determined the gross structure of 1. The relative
      and absolute stereochemistry of 1 was deduced from a combination of spectral data
      and Marfey's method for HPLC. Prior to this finding, anabeanopeptins have been
      isolated only from water-bloom-forming strains of cyanobacteria.

PMID- 12193030
TI  - New and biologically active imidazole alkaloids from two sponges of the genus
      Leucetta.
AB  - Chemical investigation of two sponges, Leucetta chagosensis and Leucetta cf
      chagosensis, collected from the Great Barrier Reef and the Fiji Islands,
      respectively, has led to the isolation of three new imidazole alkaloids (1-3),
      along with the known compounds isonaamine B (4) and naamine A (5). The structures
      of the new compounds (1-3) were elucidated by employing spectroscopic techniques
      (NMR, MS, UV, and IR). The structures of the known compounds 4 and 5 were
      determined by comparison of their (1)H and (13)C NMR spectroscopic data with
      published values. Compounds 1 and 2 were found to be cytotoxic toward several
      tumor cell lines (GI(50) values ranged from 1.3 to 7.0 microg/mL).

PMID- 12193032
TI  - Three new pyridoacridine type alkaloids from a singaporean ascidian.
AB  - Two new pyridoacridine alkaloids, kuanoniamines E and F, and a new ring-opened
      pyridoacridine alkaloid, subarine, were isolated from a Singaporean ascidian.
      Also isolated were known pyridoacridine alkaloids ascididemin and kuanoniamines A
      and D. The structures of the alkaloids were determined by spectroscopic methods.

PMID- 12193031
TI  - Ecdysteroids from a Zoanthus sp.
AB  - A new ecdysteroid, zoanthusterone, has been isolated from a marine zoanthid,
      Zoanthus sp. Ten known ecdysteroids, ponasterone A, 20-hydroxyecdysone 2-acetate,
      viticosterone E, integristerone A 25-acetate, 2-deoxy-20-hydroxyecdysone,
      ecdysone, ajugasterone C, dacryhainansterone, inokosterone, and 20
      hydroxyecdysone, have also been isolated. This is the first report of
      ecdysteroids in a Zoanthus species.

PMID- 12193033
TI  - Isotactic polymethoxydienes from the Philippines sponge Myriastra clavosa.
AB  - A specimen of the sponge Myriastra clavosa from the Philippines contained five
      new isotactic polymethoxydienes 1-5 that form a homologous series. The structures
      of the isotactic polymethoxydienes, which exhibited moderate cytotoxicity, were
      elucidated by interpretation of spectroscopic data.

PMID- 12193034
TI  - Reinvestigation of structure of porritoxin, a phytotoxin of Alternaria porri.
AB  - The structure of porritoxin, a phytotoxin of Alternaria porri, was reinvestigated
      by detailed 2D NMR analysis including (1)H-(13)C and (1)H-(15)N HMBC experiments.
      The structure of porritoxin was determined to be 2-(2'-hydroxyethyl)-4-methoxy-5
      methyl-6-(3' '-methyl-2' '-butenyloxy)-2,3-dihydro-1H-isoindol-1-one (1). Thus
      our previous proposed structure, 8-(3',3'-dimethylallyloxy)-10-methoxy-9-methyl
      1H-3,4-dihydro-2,5-benzoxazocin-6(5H)-one (2), is incorrect.

PMID- 12193035
TI  - Minor steroidal alkaloids from the marine sponge Corticium sp.
AB  - Four new steroidal alkaloids, plakinamine G (1), plakinamine H (2), 4alpha
      hydroxydemethylplakinamine B (3), and tetrahydroplakinamine A (4), along with
      three known compounds, were isolated from the marine sponge Corticium sp. The
      structures of these metabolites were elucidated largely by 1D and 2D NMR methods
      and accurate mass measurements (HR-EIMS). Compounds 1, 2, and 4 show significant
      in vitro cytotoxicity.

PMID- 12193036
TI  - A new cycloamphilectene metabolite from the Vanuatu sponge Axinella sp.
AB  - A new diterpene, N-formyl-7-amino-11-cycloamphilectene (1), was isolated from the
      apolar extract of the Vanuatu sponge Axinella sp. The structure and relative
      stereochemistry were established by spectroscopic and single-crystal X-ray
      studies.

PMID- 12193037
TI  - Two new minor polybrominated dibenzo-p-dioxins from the marine sponge Dysidea
      dendyi.
AB  - Two new minor tribromodibenzo-p-dioxins, spongiadioxin C (1) and its methyl ether
      (2), were isolated from an Australian marine sponge Dysidea dendyi, together with
      the known minor metabolites methyl ethers of spongiadioxins A (4) and B (6) and
      polybrominated diphenyl ethers (7-9). The structures of the new compounds were
      established by 1D and 2D NMR spectroscopy and confirmed by synthesis of 2 from
      diphenyl ether 9. All isolated compounds inhibited the cell division of
      fertilized sea urchin eggs.

PMID- 12193038
TI  - Two new triterpenoids from Azadirachta indica and their insecticidal activity.
AB  - Two new triterpenoids, 22,23-dihydronimocinol (1) and desfurano-6alpha
      hydroxyazadiradione (2), were isolated from a methanolic extract of the fresh
      leaves of Azadirachta indica (neem) along with a known meliacin, 7alpha-senecioyl
      (7-deacetyl)-23-O-methylnimocinolide. The structures of 1 and 2 were elucidated
      through spectral and chemical studies. Compounds 1 and 2 showed mortality for
      fourth instar larvae of the mosquito (Anopheles stephensi), with LC(50) values of
      60 and 43 ppm, respectively.

PMID- 12193039
TI  - Three new modified limonoids from Khaya senegalensis.
AB  - Three new rings B/D opened limonoids, two rearranged phragmalin limonoids named
      khayanolides D and E (1 and 2), and one limonoid glucoside named khayanoside (3)
      were isolated as insect antifeedants from the stem bark of Egyptian Khaya
      senegalensis. The structures of these compounds were established by spectroscopic
      methods, including 2D NMR and CD.

PMID- 12193040
TI  - Two new triterpene esters from the twigs of Brachylaena ramiflora from the
      Madagascar rainforest.
AB  - Bioassay-guided fractionation of a CH(2)Cl(2)/MeOH extract of the small twigs of
      Brachylaena ramiflora var. ramiflora resulted in the isolation of the two new
      triterpene esters 1 and 2 and five known triterpenoids, alpha-amyrin palmitate
      (3), beta-amyrin palmitate (4), beta-amyrin acetate (5), lupeyl acetate (6), and
      lupeol (7). The structures of the two new compounds were established as
      kairatenyl palmitate (1) and hopenyl palmitate (2) on the basis of 1D and 2D NMR
      spectroscopic data interpretation and chemical conversions. All the isolated
      compounds showed weak cytotoxicity against the A2780 human ovarian cancer cell
      line.

PMID- 12193042
TI  - Classification of endothelin receptors and antagonists in clinical development.

PMID- 12193043
TI  - (18)F-Endothelin-1, a positron emission tomography (PET) radioligand for the
      endothelin receptor system: radiosynthesis and in vivo imaging using microPET.
AB  - Positron emission tomography (PET) is a powerful technique with the sensitivity
      to image and quantify receptor-bound radioligands in vivo. Recent progress in PET
      scanner technology has resulted in the development of dedicated tomographs
      designed for small animals, with resolution that allows the delineation of
      discrete organs and their larger substructures in rats and mice. Our aim was to
      determine whether endothelin-1 (ET-1) could be labelled with (18)F, and whether
      the resulting (18)F-ET-1 would have the required pharmacokinetic properties to
      permit binding and imaging of ET receptors in vivo. (18)F-ET-1 could be produced
      in a total radiochemical yield of 5.9+/-0.7% in 207+/-3 min (n=20). Specific
      radioactivities were in the range 220-370 GBq/micromol, and the radiochemical
      purity of the isolated (18)F-ET-1 was >95%. In vivo distribution in the rat was
      studied using microPET. High levels of (18)F-ET-1 uptake were found in lung and
      kidney, whereas liver showed moderate levels of uptake. The resolution of the
      microPET scanner was sufficient to differentiate heterogeneous uptake in subrenal
      structures in the rat.

PMID- 12193041
TI  - Enhancement of iron toxicity in L929 cells by D-glucose: accelerated(re
      )reduction.
AB  - It has recently been shown that an increase in the cellular chelatable iron pool
      is sufficient to cause cell damage. To further characterize this kind of injury,
      we artificially enhanced the chelatable iron pool in L929 mouse fibroblasts using
      the highly membrane-permeable complex Fe(III)/8-hydroxyquinoline. This iron
      complex induced a significant oxygen-dependent loss of viability during an
      incubation period of 5 h. Surprisingly, the addition of L-glucose strongly
      enhanced this toxicity whereas no such effect was exerted by L-glucose and 2
      deoxyglucose. The assumption that this increase in toxicity might be due to an
      enhanced availability of reducing equivalents formed during the metabolism of L
      glucose was supported by NAD(P)H measurements which showed a 1.5-2-fold increase
      in the cellular NAD(P)H content upon addition of L-glucose. To assess the
      influence of this enhanced cellular reducing capacity on iron valence we
      established a new method to measure the reduction rate of iron based on the
      fluorescent iron(II) indicator PhenGreen SK. We could show that the rate of
      intracellular iron reduction was more than doubled in the presence of L-glucose.
      A similar acceleration was achieved by adding the reducing agents ascorbate and
      glutathione (the latter as membrane-permeable ethyl ester). Glutathione ethyl
      ester, as well as the thiol reagent N -acetylcysteine, also caused a toxicity
      increase comparable with L-glucose. These results suggest an enhancement of iron
      toxicity by L-glucose via an accelerated (re-)reduction of iron with NAD(P)H
      serving as central electron provider and ascorbate, glutathione or possibly
      NAD(P)H itself as final reducing agent.

PMID- 12193044
TI  - Augmented endothelial uptake of oxidized low-density lipoprotein in response to
      endothelin-1.
AB  - Endothelin-1 (ET-1) may be involved in the development and progression of
      atherosclerosis. Furthermore, endothelin receptor blockade was shown to reduce
      the formation of atherosclerotic lesions in experimental studies. Another potent
      pro-atherosclerotic risk factor is oxidized low-density lipoprotein (oxLDL).
      Endothelial cells mediate the uptake of oxLDL by the recently identified lectin
      like oxLDL receptor-1 (LOX-1), which accumulates in atherosclerotic lesions. In
      the present study, we analysed the effects of ET-1 on oxLDL uptake and LOX-1
      expression in primary cultures of human umbilical vein endothelial cells (HUVEC).
      ET-1 stimulated uptake of oxLDL in HUVEC, which reached a maximum after 1 h. In
      further studies, we found a similar induction of LOX-1 mRNA and protein
      expression in response to ET-1. The augmented oxLDL uptake and the increased LOX
      1 expression in response to ET-1 are mediated by the endothelin receptor B. Our
      data support a new pathophysiological mechanism by which locally and systemically
      increased ET-1 levels, e.g. in hypertensive patients, could promote LOX-1
      mediated oxLDL uptake in human endothelial cells. This mechanism could promote
      the development and progression of endothelial dysfunction and atherosclerosis.
      In addition, endothelin receptor blockade could be considered as a new anti
      atherosclerotic therapeutic principle.

PMID- 12193045
TI  - Effects of obesity on endothelium-dependent reactivity during acute nitric oxide
      synthase inhibition: modulatory role of endothelin.
AB  - This study investigated vascular reactivity in response to acetylcholine, in the
      presence of acute inhibition of nitric oxide synthase, in the carotid artery and
      aorta of obese C57Bl6/J mice fed on a high-fat diet for 30 weeks, and of control
      mice. A subgroup of obese animals was also treated with the ET(A) receptor
      antagonist darusentan (50 mg x kg(-1) x day(-1)). In vascular rings from control
      animals, acetylcholine caused endothelium-dependent contractions in the carotid
      artery, but not in the aorta. In vascular rings from obese mice, contractility to
      acetylcholine was also evident in the aorta, and that in the carotid artery was
      increased compared with control mice. ET(A) receptor blockade by darusentan
      treatment of the obese mice prevented enhanced vasoconstriction to acetylcholine,
      resulting in mild vasodilatation. Thus obesity increases endothelium-dependent
      vasoconstriction in the absence of endothelial nitric oxide. This effect can be
      completely prevented by chronic ET(A) receptor blockade, suggesting that
      endothelin modulates increased endothelium-dependent vasoconstriction in obesity.

PMID- 12193046
TI  - Peroxisome proliferator-activated receptor-gamma activators inhibit endothelin-1
      related cardiac hypertrophy in rats.
AB  - Endothelin-1 (ET-1) causes cardiac hypertrophy, and ET receptor antagonists
      inhibit the development of cardiac hypertrophy in vitro and in vivo. Peroxisome
      proliferator-activated receptor gamma (PPAR gamma), a member of the family of
      nuclear receptors, suppresses activator protein-1 (AP-1). We investigated the
      effects of the thiazolidinediones troglitazone and pioglitazone, activators of
      PPAR gamma, on cardiac hypertrophy due to pressure overload provoked by abdominal
      aortic banding (AB) in rats. Rats were divided into four groups: sham operation
      with vehicle treatment (n=5); AB surgery with vehicle treatment (n=6); AB surgery
      with troglitazone treatment (100 mg x kg(-1) x day(-1); n=5); and AB surgery with
      pioglitazone treatment (10 mg x kg(-1) x day(-1); n=8). Treatments were started 7
      days before AB surgery, and left ventricular (LV) hypertrophy was assessed 24 h
      after surgery. The ratio of LV weight/body weight (BW) was significantly
      increased in AB rats compared with sham-operated rats; treatment of AB rats with
      troglitazone or pioglitazone significantly inhibited the increase in LV
      weight/BW. Expression of ET-1 mRNA was markedly enhanced in the left ventricles
      of AB rats; treatment with troglitazone or pioglitazone lowered expression
      significantly. Suppression of cardiac hypertrophy by pioglitazone treatment was
      accompanied by a decrease in expression of the gene encoding brain natriuretic
      factor, a molecular marker for cardiac hypertrophy, in AB rats. Because the ET-1
      gene has AP-1 response elements in its 5'-flanking region, the thiazolidinediones
      troglitazone and pioglitazone may inhibit cardiac hypertrophy partly through
      suppression of AP-1-induced ET-1 gene up-regulation.

PMID- 12193047
TI  - The inhaled ET(A) receptor antagonist LU-135252 acts as a selective pulmonary
      vasodilator.
AB  - To investigate the hypothesis that the inhaled ET(A) receptor antagonist LU
      135252 acts as selective pulmonary vasodilator, we compared inhaled LU-135252 and
      inhaled nitric oxide (iNO) in an experimental model of acute lung injury (ALI),
      in a prospective, randomized, controlled animal study. A total of 30
      anaesthetized, tracheotomized and mechanically ventilated pigs underwent
      induction of ALI by repeated saline washout of surfactant. The animals were then
      randomly assigned to receive the nebulized ET(A) receptor antagonist LU-135252
      (0.3 mg x kg(-1), inhaled over 20 min; ET(A)-A group; n=10), inhaled NO (30
      p.p.m. continuously; iNO group; n=10) or nebulized saline buffer (5 ml inhaled
      over 20 min; control group; n=10). Measurements of pulmonary gas exchange and
      haemodynamics were performed hourly over a 4 h period after induction of ALI. In
      the ET(A)-A group, the arterial oxygen tension (Pa(2)) increased from 58+/-3 to
      377+/-39 mmHg at 4 h after intervention, while the intrapulmonary shunt
      (Q(S)/Q(T)) decreased from 53+/-4% to 18+/-2% (P<0.01 compared with controls). In
      the iNO group, Pa(2) increased from 62+/-4 to 224+/-48 mmHg, and Q(S)/Q(T)
      decreased from 47+/-2% to 27+/-5%, at 4 h after induction of ALI (P<0.05 compared
      with controls). In the ET(A)-A and iNO groups, the increase in mean pulmonary
      artery pressure was significantly attenuated compared with controls (ETA-A group,
      14+/-4%; iNO group, 6+/-4%; values at 4 h; P<0.01 compared with controls). In
      contrast, there were no significant differences in changes of mean arterial
      pressure and cardiac output between groups. Thus, in this experimental model of
      ALI, both inhaled LU-135252 and iNO significantly improved gas exchange and
      prevented an increase in mean pulmonary artery pressure, without significant
      systemic effects, when compared with controls. Our results indicate the
      occurrence of selective pulmonary vasodilation in both treatment groups.

PMID- 12193048
TI  - Contribution of endothelin-1 to renal activator protein-1 activation and
      macrophage infiltration in aldosterone-induced hypertension.
AB  - Aldosterone-induced hypertension is associated with renal damage that may be
      mediated by endothelin-1 (ET-1). We evaluated whether inflammatory cell
      infiltration and DNA-binding activity of the transcription factors nuclear factor
      kappa B (NF-kappa B) and activator protein-1 (AP-1) were increased in kidneys
      from aldosterone-infused rats. The role of ET-1 in these processes was evaluated
      by treating rats with the ET(A)-receptor blocker, BMS 182874. Rats were infused
      with aldosterone (0.75 microg/h) via a mini-osmotic pump and were given 1% NaCl
      in the drinking water in the absence and presence of BMS 182874 or of the
      aldosterone receptor blocker, spironolactone. Renal sections were used to assess
      inflammatory cell infiltration, which was identified immunocytochemically using
      monoclonal antibodies against macrophages (ED1+). Electrophoretic mobility shift
      assays evaluated the DNA-binding activity of NF-kappa B and AP-1 in renal tissue.
      Systolic blood pressure (BP) was increased in the aldosterone-infused group
      compared with controls (123+/-6 versus 110+/-10 mmHg, P<0.05). BMS 182874 and
      spironolactone significantly decreased BP (P<0.05). Macrophage infiltration was
      increased in the kidneys of aldosterone-infused rats compared with controls.
      Renal binding activity (arbitrary units) of AP-1, in contrast with that of NF
      kappa B, increased in aldosterone-infused rats compared with control rats (AP-1,
      4.2+/-0.3 versus 1.0+/-0.1, P<0.05; NF-kappa B, 1.6+/-0.5 versus 1.2+/-0.5). BMS
      182874 and spironolactone decreased macrophage infiltration (by 70% and 50%
      respectively) and AP-1 binding activity (1.0+/-0.3 and 0.8+/-0.3 respectively).
      In conclusion, kidneys from aldosterone-infused rats exhibited macrophage
      infiltration and increased AP-1 DNA-binding activity. These processes were
      attenuated by BMS 182874. Our findings suggest that renal damage in aldosterone
      dependent hypertension is associated with inflammatory processes that are
      mediated in part via ET-1.

PMID- 12193049
TI  - Endothelin-1 induces mucosal mast cell degranulation and tissue injury via ETA
      receptors.
AB  - The effects of endothelin-1 (ET-1) on mucosal mast cells are of special interest,
      since they may be an important component of the tissue response that occurs
      during ischaemic preconditioning or ischaemia/re-oxygenation injuries. Increasing
      doses of ET-1 were administered intravenously to anaesthetized rats. In a second
      series of experiments, animals were pretreated with the ET(A) receptor
      antagonists BQ-610 or ETR-P1/fl peptide, or with the ET(B) receptor antagonist
      IRL-1038. Intestinal perfusion changes were recorded, and the proportion of
      degranulated mast cells and the degree of mucosal damage were determined in ileal
      biopsies. ET-1 induced dose-dependent alterations in the haemodynamic and
      morphological parameters, and caused significant mast cell degranulation. These
      changes were inhibited significantly by pretreatment with the ET(A) receptor
      antagonists, but not with the ET(B) receptor antagonist. We conclude that a cross
      talk exists between endothelial cell-derived humoral mediators and the intestinal
      mast cell system.

PMID- 12193050
TI  - Three vasoactive peptides, endothelin-1, adrenomedullin and urotensin-II, in
      human tumour cell lines of different origin: expression and effects on
      proliferation.
AB  - Evidence has accumulated showing that vasoactive peptides, such as endothelin-1,
      adrenomedullin and urotensin-II, are expressed in various kinds of tumour cells.
      In the present study, the expression of endothelin-1 and endothelin receptors was
      studied in eight human tumour cell lines: T98G (glioblastoma), IMR-32 and NB69
      (neuroblastoma), BeWo (choriocarcinoma), SW-13 (adrenocortical carcinoma), DLD-1
      (colonic carcinoma), HeLa (cervical carcinoma) and VMRC-RCW (renal carcinoma).
      Reverse transcriptase-PCR showed expression of endothelin-1 mRNA in seven out of
      the eight cell lines, the exception being BeWo cells. ET(A) receptor mRNA was
      expressed in T98G, IMR-32 and NB69 cells, but weakly in the other cells. ET(B)
      receptor mRNA was expressed in IMR-32, NB69 and BeWo cells, but only weakly in
      T98G and HeLa cells. Immunoreactive endothelin was detected in the culture media
      of six out of the eight cell lines, but not in that of IMR-32 or BeWo cells.
      Treatment of T98G cells with an anti-endothelin-1 antibody or an anti
      adrenomedullin antibody for 24 h decreased cell numbers to approx. 84% and 90% of
      control respectively. Treatment with the ET(A) receptor antagonist BQ-610 (1
      microM) significantly decreased cell number to about 90% of control, whereas the
      ET(B) receptor antagonist BQ-788 had no significant effect. On the other hand,
      exogenously added endothelin-1, adrenomedullin or urotensin-II (0.1 microM) had
      no significant effects on cell number. These results suggest that endothelin-1
      acts as a paracrine or autocrine growth stimulator in tumours. The effect of
      endothelin-1 on tumour growth appears to be mediated by the ET(A) receptor.

PMID- 12193051
TI  - Tissue-dependent expression of matrix proteins in human endothelin-1 transgenic
      mice.
AB  - Endothelin-1 (ET-1) is a potent pro-fibrotic growth factor. However, little is
      known about its specific effects on the synthesis of matrix proteins in vivo. We
      used male 12-month-old ET-1 transgenic mice characterized by transgene expression
      in the kidney and (to a lesser extent) in the heart. Global cardiac and renal
      matrix protein synthesis was analysed after Sirius Red and periodate-Schiff
      staining. Specific expression of collagen types I, III and IV, laminin and
      fibronectin was examined using immunohistochemistry followed by computer-aided
      image analysis. Analysis of blood pressure revealed that mean arterial blood
      pressure was similar in ET-1 transgenic mice and controls. The total cardiac
      matrix protein content was increased in the myocardium of ET-1 transgenic mice.
      Analysis of specific cardiac matrix proteins showed increased cardiac expression
      of collagen type III (+211%; P<0.001) and laminin (+128%; P<0.01) in transgenic
      mice. The expression of collagen types I and IV and fibronectin was not altered.
      Global analysis of renal matrix proteins confirmed earlier studies showing
      pronounced interstitial fibrosis and glomerulosclerosis. Laminin expression was
      markedly increased in the glomerula (+152%; P<0.01) and even more so in the
      interstitium (+211%; P<0.001), whereas expression of collagen type III was
      reduced in glomerula (-48%; P<0.01) and interstitial tissue (-55%; P<0.01) of ET
      1 transgenic mice. In conclusion, a primary overexpression of ET-1 does not cause
      uniformly enhanced synthesis of matrix proteins. In contrast, the effects of ET-1
      on the matrix protein pattern is tissue-specific. The major renal and cardiac
      alterations in matrix proteins induced by ET-1 is a marked enhancement of laminin
      expression.

PMID- 12193052
TI  - Pattern of prepro-endothelin-1 expression revealed by reporter-gene activity in
      kidneys of erythropoietin-overexpressing mice.
AB  - Transgenic overexpression of erythropoietin (Epo) in mice increases haematocrit
      to a mean of 80% in adult mice, leading to an increase in blood viscosity and
      volume. As a consequence, renal tissue endothelin-1 (ET-1) concentrations are
      significantly elevated in erythropoietin-overexpressing (Epo+) mice (mean+/
      S.E.M; Epo+, 798+/-71; Epo-, 400+/-25 pg/g tissue; P<0.01). To investigate the
      pattern of expression of the primary translation product of the ET-1 gene, prepro
      ET-1, in kidneys of (Epo+) mice, we generated crossbred mice overexpressing the
      human EPO gene with mice carrying a reporter gene construct expressing the LacZ
      gene under the control of the human prepro-ET-1 promotor sequence (LacZ+/Epo+).
      For comparison, we generated (LacZ+/Epo-) mice from the same strains. After Bluo
      Gal staining of frozen kidney sections (n=10 in each group), intracellular blue
      precipitates as indicators of prepro-ET-1 promotor activity were detectable in
      tubular and vascular endothelium and glomerular cells in (LacZ+/Epo-) as well as
      (LacZ+/Epo+) mice. Comparison of the amount of blue precipitates by
      semiquantitative scoring showed a significant increase in reporter gene activity
      in tubular epithelium of (LacZ+/Epo+) mice (mean+/-S.E.M.; LacZ+/Epo+, 1.64+/
      0.18; LacZ+/Epo-, 1.00+/-0.19; P<0.05). Reporter gene activity was not
      significantly elevated in epithelium of small intrarenal arteries of (LacZ+/Epo+)
      mice (mean+/-S.E.M.; LacZ+/Epo+, 0.86+/-0.14; LacZ+/Epo-, 0.38+/-0.21; P=0.08)
      and was similar in glomerular cells (mean+/-S.E.M.; LacZ+/Epo+, 1.28+/-0.16;
      LacZ+/Epo-, 1.14+/-0.21; P=0.6). The main source of elevated ET-1 tissue
      concentration in kidneys of (Epo+) mice therefore seems more likely to be tubular
      than vascular endothelium or glomerular cells.

PMID- 12193053
TI  - Blood pressure of endothelin-3 null (-/-) knockout mice and endothelin A receptor
      null (-/-) knockout mice under anaesthesia.
AB  - Blood pressure (BP) and heart rate (HR) in endothelin-3 (ET-3) null (-/-)
      knockout mice and ET(A) receptor (-/-) mice were measured using the servo null
      pressure measuring technique under halothane anaesthesia. In infant ET-3 (-/-)
      mice (2-3 weeks old), mean BP and HR were 55+/-2 mmHg and 436+/-30 beats/min
      respectively. These values were not different from those in age-matched wild-type
      mice (53+/-3 mmHg and 430+/-18 beats/min respectively). Baroreflex sensitivity,
      which was calculated as the slope of the relationship between systolic BP and RR
      interval on an ECG, was also similar in ET-3 (-/-) mice (0.84+/-0.20 ms/mmHg) and
      wild-type mice (1.07+/-0.38 ms/mmHg). ET(A) receptor (-/-) mice were obtained by
      caesarean section on the expected day of delivery and tracheotomized, so that
      they would live for more than 24 h. Mean BP and HR in ET(A) receptor (-/-) mice
      were 15+/-1 mmHg and 333+/-6 beats/min respectively. These values were not
      different from those in age-matched, similarly treated wild-type mice (16+/-3
      mmHg and 308+/-10 beats/min respectively). Baroreflex sensitivity in the newborn
      ET(A) receptor (-/-) mice (0.45+/-0.15 ms/mmHg) and wild-type mice (0.31+/-0.06
      ms/mmHg) were very low compared with the values in infant wild-type mice, but not
      different between the mutant mice and their littermates. Moreover, HR in awake
      ET(A) receptor (-/-) mice (396+/-13 beats/min) was not different from that in
      wild-type mice (409+/-13 beats/min). These results show that the ET(A) receptor
      and ET-3 are not involved in cardiovascular regulation, at least during the very
      early life of the mice. A possible involvement of the ET(A) receptor in BP
      regulation, if any, seems to occur at later times and/or in some pathological
      settings.

PMID- 12193054
TI  - Forearm vasoconstriction to endothelin-1 is impaired, but constriction to
      sarafotoxin 6c and vasodilatation to BQ-123 unaltered, in patients with essential
      hypertension.
AB  - The importance of endothelin-1 (ET-1) in the pathophysiology of essential
      hypertension is unclear. We therefore compared the effects of endothelin ET(A)
      receptor blockade and the stimulation of ET(A) and ET(B) receptors, and their
      interaction with the sympathetic nervous system, in the forearm resistance
      vessels of patients with essential hypertension and healthy control subjects. A
      total of 27 untreated patients with essential hypertension (blood pressure
      >160/100 mmHg) and 25 normotensive (blood pressure <140/90 mmHg) age- and sex
      matched control subjects participated in these studies. A total of 10 patients
      and 10 controls took part in each phase. Locally active doses of study drugs were
      infused into the non-dominant brachial artery, while forearm blood flow was
      measured by venous occlusion plethysmography. A 60 min infusion of BQ-123 (an
      ET(A) receptor antagonist; 100 nmol/min) significantly increased forearm blood
      flow by 40+/-8% in hypertensive patients and by 35+/-5% in controls, with no
      difference between groups (P=0.49). Forearm vasoconstriction to ET-1 (an ET(A)
      and ET(B) receptor agonist; 5 pmol/min) for 90 min was significantly blunted in
      hypertensive patients (21+/-4%) compared with control subjects (37+/-3%;
      P=0.0001). Forearm vasoconstriction to sarafotoxin S6c (an ET(B) receptor
      agonist; 10 pmol/min) for 90 min was similar in hypertensive patients (44+/-5%)
      and control subjects (48+/-4%; P=0.95). Sympathetically mediated vasoconstriction
      produced by lower-body negative pressure was not different in hypertensive
      patients compared with controls, and was not affected by infusion of ET-1 or
      sarafotoxin S6c. There were no differences in the observed increase in forearm
      blood flow with a control vasodilator (sodium nitroprusside) or the observed
      decrease in forearm blood flow with a control vasoconstrictor (noradrenaline)
      between hypertensive patients and control subjects. BQ-123 produced a significant
      increase in forearm blood flow in hypertensive patients, consistent with the anti
      hypertensive actions of this agent. In conclusion, forearm vasoconstriction to ET
      1, but not to sarafotoxin S6c, was reduced in patients with essential
      hypertension, consistent with possible down-regulation of the ET(A) receptor in
      this condition.

PMID- 12193055
TI  - ET(A) receptor blockade protects the small intestine against
      ischaemia/reperfusion injury in dogs via an enhancement of antioxidant defences.
AB  - The aim of the present study was to determine whether the ET(A) receptor
      antagonist LU135252 can protect the mesenterium against ischaemia/reperfusion
      (I/R) damage. Direct occlusion of the superior mesenteric artery was performed
      for 30 min in two groups of dogs. Declamping was followed by 90 min of
      reperfusion. Mesenteric release of ET-1 was studied in series 1 (n=6). In series
      2, 5 min before cross-clamping, the treated group (n=7) received an intravenous
      bolus of LU135252 (5 mg/kg), whereas the control group (n=6) was given vehicle.
      Mean arterial blood pressure and mesenteric blood flow were recorded. Mesenteric
      venous and systemic arterial serum lactate and glucose, plasma creatine kinase
      and free radical concentrations were determined at 15 min intervals. Ischaemia
      for 30 min induced a significant increase (P<0.05) in mesenteric ET-1 release
      (1594+/-526 pg/min, compared with 343+/-258 pg/min at baseline), which had
      returned to baseline after 20 min of reperfusion. LU135252 administration
      significantly decreased mesenteric blood flow during ischaemia (204+/-23%)
      compared with controls (320+/-34%, P<0.05). In contrast, mesenteric blood flow
      was higher in the treated group (120+/-19% compared with 82+/-7%; P<0.05) after
      90 min of reperfusion. Mesenteric lactate production was reduced by ET(A)
      antagonist administration under ischaemia (0.77+/-0.02 mmol/l) compared with
      controls (1.36+/-0.04 mmol/l; P<0.01). Lower levels of venous creatine kinase
      were present in the treated group during ischaemia as well as after reperfusion
      (120+/-7% compared with 150+/-16%; P<0.01). Administration of LU135252 also
      improved the total scavenger capacity of the mesenteric bed during ischaemia
      [(15.9+/-3.9)x10(6) compared with (6.4+/-3.6)x10(6) relative light units; P<0.05]
      and early reperfusion [(8.7+/-3.1)x10(6) compared with (1.1+/-2.9)x10(6) relative
      light units]. Thus ET-1 is involved in I/R-induced disturbances in the intestine.
      LU135252 seems to counteract these changes, in part by increasing the antioxidant
      capacity of the mesenterium.

PMID- 12193056
TI  - Role of endothelin during experimental Trypanosoma cruzi infection in rats.
AB  - Chagas' disease is caused by the intracellular protozoan Trypanosoma cruzi. Here
      we have investigated the role of endothelin-1 in T. cruzi acute infection in
      rats, using the orally active ET(A) receptor antagonist BSF-461314. Treatment
      with BSF-461314 markedly increased parasitaemia, but animals managed to control
      the infection by day 15. Histopathological analysis of heart tissue at the end of
      the acute phase showed greater numbers of parasite nests in BSF-461314-treated
      animals. The perfusion of isolated rat hearts from infected animals with
      bradykinin failed to induce an increase, and actually reduced, coronary blood
      flow. Pretreatment with BSF-461314 prevented changes in coronary flow induced by
      T. cruzi infection. Together these results demonstrate that endothelin-1, through
      ET(A) receptor activation, contributes to the protective immune response against
      acute T. cruzi infection. Moreover, these data suggest that endothelin-1 is a
      mediator of impaired endothelium-dependent vasomotion in the coronary
      microcirculation associated with acute T. cruzi infection.

PMID- 12193057
TI  - Nitric oxide inhibits endothelin-1 production through the suppression of nuclear
      factor kappa B.
AB  - We have reported previously that the nitric oxide (NO) donor FK409 [(+/-)-(E)-4
      ethyl-2-[(E)-hydroxyimino]-5-nitro-3-hexanamide] improved renal dysfunction as
      well as renal lesions in rats with ischaemia/reperfusion injury. We also found
      that FK409 substantially reduced endothelin-1 (ET-1) production in cultured
      vascular endothelial cells (ECs). Nuclear factor kappa B (NF-kappa B) is known to
      play a key role in the development of ischaemic disorders through regulation of
      the expression of a variety of genes. In the present study, we examined the
      effects of FK409 on ET-1 production in cultured pig aortic ECs, and the possible
      involvement of NF-kappa B in the inhibitory effect of NO on ET-1 production.
      FK409 significantly attenuated basal and tumour necrosis factor-alpha (TNF-alpha)
      induced preproET-1 mRNA expression in ECs. In addition, FK409 diminished basal
      and TNF-alpha-stimulated NF-kappa B activation in ECs. Pretreatment with N
      benzyloxycarbonyl-Ile-Glu(O-t-Bu)-Ala-leucinal or BAY 11-7082, both of which are
      suppressors of NF-kappa B activation, effectively attenuated basal and TNF-alpha
      induced ET-1 mRNA expression. These findings suggest that the suppression of NF
      kappa B activation is at least partly involved in the FK409-induced inhibition of
      ET-1 production in ECs. We propose that NF-kappa B activation plays an important
      role in ET-1 production.

PMID- 12193058
TI  - Comparison of red wine extract and polyphenol constituents on endothelin-1
      synthesis by cultured endothelial cells.
AB  - Regular consumption of red wine reduces mortality from coronary heart disease.
      This observation has been attributed to the anti-thrombotic effects of ethanol
      and to the antioxidant properties of polyphenolic compounds present in red wine.
      Here we show that an extract of red wine polyphenols causes a concentration
      dependent inhibition of endothelin-1 synthesis in cultured bovine aortic
      endothelial cells. This action was associated with modifications in
      phosphotyrosine staining, indicating that the active components of red wine cause
      specific modifications of tyrosine kinase signalling. Thus inhibition of
      endothelin-1 synthesis by red wine may reduce the development of atherosclerosis,
      and hence decrease coronary heart disease.

PMID- 12193059
TI  - The immunosuppressive drug mycophenolic acid reduces endothelin-1 synthesis in
      endothelial cells and renal epithelial cells.
AB  - Several studies have demonstrated that endothelin-1 (ET-1) plays an important
      pathophysiological role in ischaemic renal failure and drug-induced renal injury,
      such as cyclosporine A (CsA)- and tacrolimus-associated nephrotoxicity. This
      study aimed to investigate whether the new immunosuppressive drug mycophenolic
      acid (MPA), which in contrast with CsA and tacrolimus lacks nephrotoxic side
      effects, modulates ET-1 synthesis in endothelial cells and renal epithelial
      cells. ET-1 release by cultured human umbilical vein endothelial cells (HUVEC),
      human renal artery endothelial cells (RAEC) and rabbit proximal tubule cells was
      measured with a specific ELISA. ET-1 mRNA expression was investigated by reverse
      transcription-PCR. MPA (2.5-50 microg/ml) induced a significant decrease in ET-1
      mRNA expression (minimum 51.8+/-3.8% of control; P<0.001) in HUVEC and RAEC.
      After a 48 h incubation with MPA (1-50 microg/ml), a significant decrease in ET-1
      release per culture well (minimum 56.8+/-1.7%; P<0.001) and DNA content per
      culture well (minimum 58.7+/-1.9%; P<0.001) was observed with HUVEC and RAEC,
      whereas ET-1 release referred to the DNA content in the corresponding culture
      well did not differ significantly from controls. In rabbit proximal tubule cells,
      ET-1 release referred to the cell number in the corresponding culture well was
      also reduced after incubation with MPA (minimum 86.2+/-2.4%; P<0.05). This study
      provides evidence that, in contrast with CsA and tacrolimus, MPA does not
      stimulate ET-1 synthesis. The present results might explain the clinical
      observation that renal function often improves when CsA or tacrolimus is replaced
      by mycophenolate mofetil.

PMID- 12193060
TI  - HMG-CoA reductase inhibition and PPAR- alpha activation both inhibit cyclosporin
      A induced endothelin-1 secretion in cultured endothelial cells.
AB  - The use of cyclosporin A (CsA) in solid organ transplantation has been shown to
      be associated with the development of hypertension and nephrotoxicity. Several
      mechanisms, including endothelin (ET)-1-mediated systemic vasoconstriction, are
      considered to be responsible for CsA-induced hypertension. This study shows that:
      (i) incubation of CsA (1 microg) with bovine aortic endothelial cells leads to
      increased ET secretion by+40%; (ii) the use of compactin, the 3-hydroxy-3
      methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitor and fibric acid, the
      peroxisome-proliferator-activated receptor (PPAR)-alpha activator, inhibit the
      CsA-induced ET secretion to the level below the basal ET secretion, by -32% and 
      26% respectively; (iii) both inhibitions were reversed by the addition of
      mevalonate, suggesting communication between the HMG-CoA reductase product and
      PPAR-alpha pathway. The present findings may be of significant clinical
      relevance, since statins and fibrates beyond their hypolipidaemic action may
      represent a potential therapeutic tool in the treatment or prophylaxis of CsA
      associated side effects. Furthermore, we suggest that the mevalonate metabolism
      would interfere with PPAR-alpha activity.

PMID- 12193061
TI  - Sequence analysis and expression of the mouse full-length vasoactive intestinal
      contractor/endothelin-2 gene (EDN2): comparison with the endothelin-1 gene
      (EDN1).
AB  - Vasoactive intestinal contractor (VIC)/endothelin-2 (ET2) is a vasoactive peptide
      hormone comprising 21 amino acids. The complete nucleotide sequence of the full
      length gene encoding preproVIC (PPVIC) was determined. The PPVIC gene contains
      five exons that span 6 kb and shows a duplication on exons 2 and 3, coding for
      the VIC and VIC-like peptides respectively. Similarities between the genomic
      organization of the PPVIC/preproET2 and preproendothelin-1 genes suggest that the
      two are distantly related. PPVIC gene expression was observed in foetal and adult
      mouse intestine. The expression level in adults was approx. 10-fold higher than
      in the foetus, suggesting an involvement of VIC in intestinal development.

PMID- 12193062
TI  - Characterization of PgPepO, a bacterial homologue of endothelin-converting enzyme
      1.
AB  - PgPepO is a homologue of endothelin-converting enzyme-1 (ECE-1), with which it
      shares 31% identity. PgPepO was isolated from the periodontal pathogen
      Porphyromonas gingivalis. Recent studies have suggested a link between
      periodontal and cardiovascular disease, and several groups have suggested that
      bacterial and viral infections may contribute to the latter. P. gingivalis
      possesses the ability to invade, and multiply within, aortic endothelial cells
      and has been localized to atherosclerotic plaques. PgPepO was expressed and
      purified to homogeneity and we have begun detailed functional analysis, in terms
      of substrate preference and inhibitor specificity, in order to provide active
      site comparisons with other members of the neprilysin (NEP)/ECE family. PgPepO
      possesses similar substrate specificity to ECE-1 and has been shown to cleave big
      endothelin-1 (big ET-1), big ET-2 and big ET-3, converting the substrates into
      their respective mature endothelin peptides. Substance P, angiotensin I,
      angiotensin II and neurotensin are all cleaved at multiple sites by PgPepO and
      the kinetics of these reactions have been compared. The potent vasoconstrictor
      urotensin II is not hydrolysed by PgPepO. Cleavage of bradykinin by PgPepO occurs
      at the Pro(7)-Phe(8) bond and is inhibited by the NEP and ECE-1 inhibitor
      phosphoramidon in a pH-dependent fashion (IC(50) =10 microM at pH 7.0) but not by
      thiorphan, an NEP-specific inhibitor. PgPepO activity is completely inhibited by
      EDTA. Characterization of this enzyme is important in elucidating possible links
      between periodontal pathogens and cardiovascular disorders such as
      atherosclerosis, and provides an opportunity to gain structural information on a
      bacterial protein with striking similarity to human ECE-1.

PMID- 12193063
TI  - Expression, purification and characterization of the monomeric and dimeric forms
      of soluble bovine endothelin converting enzyme-1a.
AB  - In this study, the catalytic domain of bovine endothelin converting enzyme-1a
      (ECE-1a) was cloned into a baculovirus transfer vector behind the human alkaline
      phosphatase signal sequence. The recombinant baculovirus was then used to infect
      High Five(TM) insect cells in suspension culture. Both the monomeric (85 kDa) and
      dimeric (170 kDa) forms of soluble ECE-1a were purified to electrophoretic
      homogeneity from concentrated culture media following sequential concanavalin A,
      SP-Sepharose, Mono Q and gel filtration column chromatography. Typically,
      approximately 11 mg of ECE-1a monomer and 6 mg of dimer were obtained from l
      litre of culture medium. No interconversion of the two forms was detected after
      purification. Both forms of ECE-1a had a pH optimum of 7.0, were maximally
      stimulated by NaCl at a concentration of 500 mM, and were inhibited to the same
      extent by metalloprotease inhibitors such as phosphoramidon and EDTA. However, in
      kinetic studies using big endothelin-1 (ET-1) as a substrate, the K(m) and k(cat)
      values for the monomer were 2.2 microM and 1.6 min(-1) respectively, while those
      of the dimer were 1.4 microM and 4.9 min(-1) respectively. These results show
      that, although the two forms of ECE-1a behave similarly in many aspects, the
      dimeric enzyme is more efficient in catalysing the conversion of big ET-1 to ET
      1. The present protocol can be utilized to prepare large quantities of both forms
      of ECE-1a for further biochemical and structural characterization.

PMID- 12193065
TI  - Effects of the ECE/NEP inhibitor CGS 34225 on the big ET-1-induced pressor
      response and plasma atrial natriuretic peptide concentration in conscious rats.
AB  - CGS 34226 is a thiol-containing, potent dual inhibitor of endothelin converting
      enzyme-1 (ECE-1) and neutral endopeptidase 24.11 (NEP) with IC(50) values of 11
      and 5 nM respectively. The purpose of the present study was to characterize the
      inhibitory effects of CGS 34225, an orally active prodrug of CGS 34226, on ECE-1
      and NEP in vivo. The effects on ECE-1 and NEP were assessed by determining the
      inhibition of big endothelin-1 (big ET-1)-induced increases in mean arterial
      pressure (MAP) and increases in plasma atrial natriuretic peptide (ANP)
      concentrations respectively, in conscious rats. Thirty and 120 min after the
      administration of vehicle, big ET-1 (0.3 nmol/kg, intravenously; i.v.) produced
      pressor responses of approximately 800 mmHg.min (area under the curve for change
      in MAPxtime). Treatment with CGS 34225 at 1 mgEq/kg, per os (p.o.), decreased the
      pressor effect of big ET-1 by 39 and 53% at 30 and 120 min respectively (P<0.05,
      both times). Increasing the dose of CGS 34255 to 30 mgEq/kg, p.o., resulted in
      greater inhibition, 84 and 92% (P<0.05) at 30 and 120 min respectively.
      Furthermore, at this higher dose, the inhibitory effect on ECE-1 was long
      lasting, averaging 86, 75 and 30% (P<0.05, all times) at 4, 8 and 24 h
      respectively. In rats treated with vehicle, the infusion of ANP at 450 ng/kg per
      min i.v. resulted in plasma ANP concentrations of 3.9-4.8 ng/ml that remained
      relatively constant for 4 h. Treatment with CGS 34225 at 10 mgEq/kg, p.o.,
      increased the ANP level to 7.7+/-1.0 and 10.6+/-1.8 ng/ml at 1 and 4 h after
      dosing (P<0.05, both times). These data demonstrate that CGS 34225 is a potent,
      orally active and long-acting inhibitor of ECE-1 and NEP in vivo. It is
      anticipated that compounds with this dual function may be useful in the treatment
      of cardiovascular diseases where the ET system plays a pathogenic role and the
      potentiation of ANP elicits therapeutic benefits.

PMID- 12193066
TI  - Pharmacology of endothelin receptor antagonists ABT-627, ABT-546, A-182086 and A
      192621: in vitro studies.
AB  - Endothelins (ETs), 21-amino-acid peptides involved in the pathogenesis of various
      diseases, bind to ET(A) and ET(B) receptors to initiate their effects. Based on
      the same core structure, we have developed four small-molecule ET receptor
      antagonists, ABT-627, ABT-546, A-182086 and A-192621, which exhibit difference in
      selectivity for ET(A) and ET(B) receptors. In this report, we compare the potency
      and selectivity of these four antagonists in inhibiting (125)I-labelled ET-1
      binding to cloned human ET(A) and ET(B) receptors, and in blocking ET-1-induced
      functional responses (arachidonic acid release and phosphatidylinositol
      hydrolysis).

PMID- 12193064
TI  - CGS 34226, a thiol-based dual inhibitor of endothelin converting enzyme-1 and
      neutral endopeptidase 24.11.
AB  - Endothelins (ETs) are potent vasoconstrictors and have been implicated in the
      pathogenesis of various cardiovascular and renal diseases. In contrast, atrial
      natriuretic peptide (ANP) is a potent vasorelaxant and diuretic agent, which is
      mainly degraded by neutral endopeptidase 24.11 (NEP) in vivo. Thus, compounds
      that can suppress the biosynthesis of ETs by inhibiting endothelin converting
      enzymes (ECEs), which catalyse the final step of post-translational processing of
      the vasoconstrictors, while simultaneously potentiating the levels of ANP by
      inhibiting NEP may have novel therapeutic utility. Through targeted screening of
      our compound library and subsequent optimization, CGS 34226 was identified as a
      potent, dual inhibitor of ECE-1 and NEP, inhibiting the enzymes with respective
      IC(50) values of 11 and 4.6 nM. In vivo, CGS 34226 suppressed the big endothelin
      1 (big ET-1)-induced pressor response dose-dependently. At 15 and 90 min after an
      intravenous dose of 30 mg/kg in anaesthetized rats, this compound inhibited the
      big ET-1-induced effect by 79% and 65% respectively. In addition, CGS 34226
      increased plasma ANP immunoreactivity by 120% up to 4 h after an intravenous dose
      of 10 mg/kg in conscious rats infused with ANP at a rate of 450 ng/kg per min,
      intravenously. These results show that CGS 34226 is a potent dual inhibitor of
      ECE-1 and NEP in vitro and in vivo and that the compound may represent a novel
      agent for the treatment of cardiovascular and renal dysfunction.

PMID- 12193067
TI  - Pharmacology of endothelin receptor antagonists ABT-627, ABT-546, A-182086 and A
      192621: ex vivo and in vivo studies.
AB  - Endothelins (ETs), 21-amino-acid peptides involved in the pathogenesis of various
      diseases, bind to ET(A) and ET(B) receptors to initiate their effects. Based on
      the same core structure, we have developed four small-molecule ET receptor
      antagonists, ABT-627 (atrasentan), ABT-546, A-182086 and A-192621, which exhibit
      differences in selectivity for ET(A) and ET(B) receptors. In this report, we
      compare the efficacy, potency and pharmacokinetic properties of these four
      antagonists, including potency in inhibiting ET-1- or Sarafotoxin 6c-induced
      vessel constriction in isolated arteries and efficacy in antagonizing ET-1-, big
      ET-1- or Sarafotoxin 6c-induced pressor responses in rats.

PMID- 12193068
TI  - Effects of exercise training on expression of endothelin-1 mRNA in the aorta of
      aged rats.
AB  - Aging impairs endothelial function and the vascular tone regulation, although the
      precise mechanism remains unclear. Endothelin-1 (ET-1) is a potent
      vasoconstrictor peptide produced by vascular endothelial cells. Because ET-1 has
      a potent vasoconstrictor effect on vessels, it may be involved in the regulation
      of vascular tonus. We hypothesized that aging causes a decrease in ET-1
      expression in aorta, and that exercise training improves the aging-induced
      decrease in ET-1 expression in aorta. This study was performed to examine whether
      gene expression of ET-1 in the aorta of rats is altered by aging and subsequent
      exercise training. We studied expression of ET-1 mRNA in the aortas of sedentary
      young rats (Sedentary young group, 4 months old), sedentary aged rats (Sedentary
      aged group, 23 months old), and swim trained aged rats (Training aged group, 23
      months old; swimming training for 8 weeks, 5 days/week, 90 min/day). The
      expression of ET-1 mRNA in the aorta was analysed by real-time quantitative PCR.
      Body weight and resting heart rate were significantly lower in the Training aged
      group compared with the Sedentary aged group. These results suggest that the
      Training aged rats exhibited physiological effects from exercise training. The
      expression of ET-1 mRNA in the aorta was markedly lower in Sedentary aged group
      compared with the Sedentary young group, whereas it was significantly higher in
      Training aged group compared with the Sedentary aged group. These results show
      that the expression of ET-1 mRNA in the aorta is decreased by aging, and that the
      expression is increased by exercise training. Therefore, the present study
      provides a possibility that exercise training improves endothelial function
      through up-regulation of the aging-induced decrease in ET-1 expression in the
      aorta.

PMID- 12193069
TI  - Comparison of the effects of atherosclerosis and nitrate therapy on responses to
      nitric oxide and endothelin-1 in human arteries in vitro.
AB  - The effect of previous nitrate therapy on vascular responses to endothelin-1 (ET
      1) and NO was investigated in human internal mammary artery (IMA) in vitro.
      Cumulative concentration-response curves to ET-1 were constructed in rings of IMA
      and the data grouped into IMA from patients given nitrates prior to the bypass
      graft operation (nitrate group) and IMA from patients who were not prescribed
      nitrates (control group). No significant differences were observed between the
      two groups, either in EC(50) value [P>0.05; 3.5 nM (2.4-5.3 nM; 95% confidence
      interval) and 4.8 (2.2-10 nM), nitrate and control groups respectively] or E(max)
      (P>0.05; 78+/-7.5% and 85+/-9.5%, nitrate and control group respectively). No
      significant differences in concentration-response curves to the NO-donor
      diethylamine NONOate (DEA/NO) in rings of IMA pre-constricted with 10 nM ET-1
      were observed between control and nitrate groups [P>0.05; EC(50) values 0.59
      (0.21-1.7) microM and 0.17 (0.03-0.87) microM; E(max) 110+/-5.7% and 112+/-4.5%,
      nitrate and control groups respectively]. Concentration-response curves to DEA/NO
      constructed in normal coronary artery were not significantly different from those
      in coronary artery obtained from patients with ischaemic heart disease (IHD)
      [P>0.05; E(max) 124+/-11% and 138+/-20%; EC(50) 0.08 (0.02-0.30) microM and 0.23
      (0.02-24) microM, normal and IHD respectively]. These data indicate that nitrate
      therapy does not induce long-term changes in the ET signalling pathway.
      Furthermore, the tolerance to nitrate therapy is likely to be because of impaired
      bio-transformation of the drug rather than reduced sensitivity of the media to
      NO. The similar responses to DEA/NO in normal and atherosclerotic coronary artery
      suggests that the reduced vasodilator responses in IHD is because of a
      dysfunctional endothelium and is not mediated by changes in the NO signalling
      pathway of the smooth muscle.

PMID- 12193070
TI  - Endothelin-1 (1-31) induces a thiorphan-sensitive release of eicosanoids via
      ET(B) receptors in the guinea pig perfused lung.
AB  - Maturation of big endothelin-1 (big ET-1) commonly produces the 21 amino acid
      vasoactive ET-1, which binds two ET receptors (ET(A) and ET(B)) to produce its
      effects. In the guinea pig, the systemic administration of ET-1 produces a
      bronchoconstrictor response that is mediated indirectly via the release of
      thromboxane A(2) through ET(B) receptor activation. A new potent metabolite of
      big ET-1, ET-1 (1-31), has been reported to act as an ET(A) receptor selective
      agonist. In this study we investigated the effects of ET-1 (1-31), compared with
      ET-1, on the release of eicosanoids in the isolated and perfused guinea pig lung.
      We also clarified the implication of ET receptors in these effects using
      selective ET(A) or ET(B) receptor antagonists, BQ-123 and BQ-788 respectively.
      Finally, using the neutral endopeptidase 24.11 (NEP 24.11) inhibitor, thiorphan,
      we determined the involvement of this enzyme on ET-1 (1-31) effects. Infusion of
      ET-1 (1-31) (50 nM) stimulates a marked release of thromboxane A(2) and
      prostacyclin equivalent to that observed with a ten times lower concentration of
      ET-1 (5 nM). BQ-788 (5 nM and 10 nM), but not BQ-123 (1 microM), decreases the
      release of thromboxane A(2) and prostacyclin triggered by both agonists.
      Interestingly, thiorphan (25 microM) abolishes the eicosanoid-releasing
      properties of big ET-1 (100 nM) and ET-1 (1-31). This study demonstrates that ET
      1 (1-31) is less potent than ET-1 in stimulating the release of eicosanoids
      through ET(B) receptor activation in the guinea pig perfused lung. Moreover, the
      inhibitory properties of thiorphan indicate the possible existence of a bioactive
      metabolite of ET-1 (1-31). We therefore suggest that NEP 24.11 in the pulmonary
      vasculature, is implicated in the cleavage of ET-1 (1-31) to produce ET-1 which
      will further act on both ET receptors.

PMID- 12193071
TI  - Endothelin signalling and regulation of protein kinases in glomerular mesangial
      cells.
AB  - The molecular mechanisms of endothelin (ET)-dependent activation of extracellular
      signal-regulated kinase (ERK)and p38 mitogen-activated protein (MAP) kinase were
      studied in rat and human renal glomerular mesangial cells. ET-1 induced a rapid
      and transient activation of Ras in renal mesangial cells, which was dependent
      upon the formation of the Shc/Grb2/Sos1 signalling complex and resulted in
      transient ERK activation. We have observed that Pyk2, a calcium-dependent
      cytoplasmic tyrosine kinase, was expressed in human renal mesangial cells and was
      tyrosine phosphorylated after ET-1 treatment. ET-1-induced activation of p38 MAPK
      pathway (but not ERK pathway) was inhibited in human and in rat glomerular
      mesangial cells expressing dominant-negative form of Pyk2, suggesting the
      engagement of Pyk2 in ET-1-mediated activation of p38 MAP kinase cascade.
      Contractive responsiveness of renal mesangial cells was shown to depend on
      activation of the p38 MAP kinases. Thus, p38 MAP kinase stimulation could perhaps
      partially account for ET-1 contractive properties, whereas ET-1-induced cell
      proliferation occurs primarily via Ras-dependent activation of the ERK.

PMID- 12193072
TI  - Chronic elevated endothelin-1 concentrations regulate mitogen-activated protein
      kinases ERK 1 and ERK 2 in vascular smooth muscle cells.
AB  - Increased endothelin-1 (ET-1) levels are found in patients with atherosclerosis.
      ET-1 is known to increase the mitotic response of different growth factors
      already at threshold concentrations. The aim of this study was to investigate the
      influence of ET-1 on the mitogen-activated protein (MAP) kinases, extracellular
      signal-regulated protein kinase (ERK) 1 and ERK 2. Smooth muscle cells were
      incubated with ET-1 at a concentration of 10(-7) M for 1-120 h. ERK 1 and ERK 2
      were determined in cell homogenates by electrophoresis. Specific antibodies were
      used to investigate the amount of ERK 1 or ERK 2 in the homogenate. The
      functional activity of ERK 1 and ERK 2 was determined. Immunofluorescence
      microscopy was performed to analyse the translocation of the MAP kinases into the
      nucleus. ET-1 incubation for 12 h decreased ERK 1 concentration by -51%. After 36
      h of ET-1 application the concentration of ERK 1 increased to control levels
      again. When the cells were incubated for 120 h ERK 1 rose by +65% above control.
      The incubation with ET-1 in the presence of an ET(A) receptor antagonist
      inhibited the increase of ERK 1. ERK 2 showed a comparable time course with an
      initial decrease in the protein concentration followed by an increase after 120
      h. Incubation with an ET(A) receptor antagonist inhibited the increase in protein
      concentration after 120 h. However, the functional activity of both MAP kinases
      remained unchanged between 1 and 120 h. Especially, after 120 h of ET-1
      incubation no translocation into the nucleus was observed. However, an additional
      stimulus with angiotensin II resulted in translocation of ERK into the nucleus.
      These data show that ET-1 increases the protein concentration of MAP kinases ERK
      1 and ERK 2 but not their basal activity. Only an additional stimulation with
      angiotensin II leads to the translocation of ERK into the cell nucleus.

PMID- 12193073
TI  - Role of endothelin-1 receptors in the sarcolemma membrane and the nuclear
      membrane in the modulation of basal cytosolic and nuclear calcium levels in heart
      cells.
AB  - Our previous work in heart cells showed that the nuclear envelope membranes
      possess receptors, such as those for angiotensin II. Using non-working single
      cells from the hearts of 10-day chick embryos and the confocal microscopy
      technique, our present results show that stimulation of endothelin-1 (ET-1)
      receptors at the sarcolemma membrane induced a dose-dependent sustained increase
      in basal cytosolic and nuclear calcium levels that was insensitive to the ET(A)
      and ET(B) receptor antagonists BQ123 and BQ788. The cytosolic application of ET-1
      induced a dose-dependent increase in the sustained basal nuclear Ca(2+)
      concentration that was insensitive to BQ123 and BQ788. The ET-1 receptors at the
      nuclear envelope membrane were more sensitive to ET-1 than those located at the
      sarcolemma membrane of heart cells. Cytosolic application of ET-1 prevented
      sustained basal cytosolic Ca(2+) uptake by the nuclei. The use of an ET-1
      fluorescent probe demonstrated the presence of ET-1 receptors at both the
      sarcolemma membrane and the nuclear envelope membrane. Thus our results suggest
      that ET-1 receptors that are insensitive to BQ123 and BQ788 are present at both
      the sarcolemma and nuclear envelope membranes. Extracellular and cytosolic ET-1
      may play a role in regulating basal cytosolic and nuclear Ca(2+) levels in heart
      cells.

PMID- 12193074
TI  - Cyclic stretch and endothelin-1 mediated activation of chloride channels in
      cultured neonatal rat ventricular myocytes.
AB  - To date various types of Cl(-) currents have been recorded in cardiac myocytes
      from different regions of the heart and from different species. Most of these are
      silent under basal conditions, but are rapidly activated under the influence of
      various agonists or physical stress that, in the long term, also lead to
      development of hypertrophy. Previously, we identified three different Cl(-)
      channel activities in neonatal rat cardiomyocytes: (i) Ca(2+) regulated, (ii)
      cAMP regulated (cystic fibrosis transmembrane conductance regulator Cl(-)
      channels) and (iii) osmoregulated Cl(-) channels. In this study, we examined
      comparatively the effects of cyclic stretch and endothelin-1 (ET-1) on Cl(-)
      channel activity in primary cultures of neonatal rat ventricular myocytes using
      an (125)I-efflux assay. About 4 min after the start of the (125)I-efflux (mean
      basal rate amounts 6.3% of total (125)I incorporated/min), the addition of 10 nM
      ET-1 or the application of cyclic stretch rapidly and transiently increased
      (125)I-efflux by 3.8%/min and 0.8%/min respectively above the basal rate. The
      stretch induced (125)I-efflux rate could be blocked by 100 microM Gd(3+) but it
      had no effect on the ET-1 response. After 24 h stimulation by ET-1 or cyclic
      stretch the myocytes responded by hypertrophy which is detected by increases of
      (3)H-leucine incorporation into protein and protein/DNA ratio. In conclusion,
      cyclic stretch as well as ET rapidly and transiently activate Cl(-) channels in
      rat neonatal cardiomyocytes. The results suggest that the activation of distinct
      types of Cl(-) channels (co)transduce the stretch- and agonist-induced
      hypertrophic responses in these myocytes.

PMID- 12193075
TI  - Effects of aging and subsequent exercise training on gene expression of
      endothelin-1 in rat heart.
AB  - Endothelin-1 (ET-1) is produced by endothelial cells and cardiac myocytes. ET-1
      has potent positive inotropic and chronotropic effects on heart and induces
      myocardial cell hypertrophy. We investigated whether gene expression of ET-1 in
      rat hearts is altered by aging and subsequent exercise training. We also
      investigated whether gene expression of atrial natriuretic peptide (ANP) and
      brain natriuretic peptide (BNP), which participate in some pathological cardiac
      conditions, in the rat hearts is altered by aging and subsequent exercise
      training. We studied mRNA expression of ET-1, ANP and BNP in hearts of sedentary
      young rats (Sedentary young; 4 months old), sedentary aged rats (Sedentary aged;
      23 months old), and swim-trained aged rats (Trained aged; 23 months old, swimming
      training for 8 weeks). The left ventricle weight mass index for body weight and
      left ventricular end-diastolic dimension were significantly higher in the Trained
      aged group compared with the Sedentary aged group. These results showed that
      Trained aged rats developed cardiac hypertrophy with improvement of cardiac
      function. The mRNA expression of ET-1 in the heart was significantly higher in
      Sedentary aged group compared with Sedentary young group, and was significantly
      higher in the Trained aged group compared with the Sedentary aged group. The mRNA
      expression of ANP and BNP in the heart was significantly higher in Sedentary aged
      group compared with Sedentary young group, and was significantly higher in the
      Trained aged group compared with the Sedentary aged group. The present results
      show that mRNA expression of ET-1 in the heart is increased by aging, and that
      the mRNA expression is further increased by exercise-induced cardiac hypertrophy,
      suggesting that ET-1 in the heart may participate in these physiological cardiac
      adaptations.

PMID- 12193076
TI  - Potentiation by endothelin-1 and vasopressin of sympathetic vasoconstriction in
      male and female rats.
AB  - The aim of this study was to analyse the modulatory role of endothelin-1 and
      vasopressin in sympathetic vasoconstriction, and whether there are gender
      differences in this modulatory role. Electrical field stimulation (4 Hz, 0.2 ms
      pulse duration at supramaximal voltage of 70 V, for 1 s), applied to isolated
      segments from rat tail arteries, produced a contraction that was lower in the
      vascular segments from female than in those from male rats. This arterial
      contraction was potentiated in a concentration-dependent way by endothelin-1 (10(
      10)-3 x 10(-9) mol/l) and vasopressin (10(-12) - 10(-10) mol/l), and the
      increment produced by endothelin-1 was similar in the arteries of both, whereas
      the increment induced by vasopressin was higher in the arteries from male than in
      those from female rats. These results suggest that endothelin-1 and vasopressin
      potentiate the vasoconstriction to sympathetic stimulation, and this potentiating
      effect of vasopressin may be higher, whereas that of endothelin-1 may be similar,
      in males than in females.

PMID- 12193077
TI  - Modulation of ET(B) receptor-induced arginine-vasopressin secretion by N-methyl-D
      aspartate (NMDA) and gamma-aminobutyric acid (GABA)-dependent mechanisms in
      hypothalamo-neurohypophysial explants.
AB  - The endothelins (ETs) stimulate the secretion of arginine-vasopressin (AVP) in
      vivo and in vitro. The activation of hypothalamic ET(B) receptors increases AVP
      release, but the neurotransmitters mediating these responses are not known. In
      the compartmentalized hypothalamo-neurohypophysial explant model, the overall
      basal release of AVP was 53+/-17 pg x h(-1) x PP(-1) (where PP is posterior
      pituitary). ET(B) receptor activation in hypothalamic sites by 1 nM IRL1620 dose
      dependently increased AVP secretion, with a maximal response of 340+/-70% of
      basal x h(-1) x PP(-1), whereas 1 nM ET-1, the ET(A) receptor-selective agonist,
      inhibited AVP release to 44+/-8% x h(-1) x PP(-1). Addition of MK801 along with
      IRL1620 inhibited AVP release to a value no different from basal (122+/-41% x h(
      1) x PP(-1)). In contrast, 10 microM DNQX [6,7-dinitroquinozaline-2,3-(1H,4H)
      dione] did not block ET(B) receptor-induced AVP release (326+/-73% x h(-1) x PP(
      1)), and nor did non-selective alpha-adrenergic receptor antagonism. The GABA(A)
      (where GABA is gamma-aminobutyric acid) receptor agonist muscimol (10 microM)
      inhibited AVP release in response to IRL1620 (127+/-30% x h(-1) x explant(-1)).
      These data suggest that AVP release induced by activation of hypothalamic ET(B)
      receptors is mediated by a hypothalamic N-methyl-D-aspartate (NMDA) receptor
      mediated mechanism. In turn, the local release of GABA associated with NMDA
      activation may exert an inhibitory influence and dampen the AVP secretory
      response.

PMID- 12193078
TI  - Expression of endothelin-1 and vasoactive intestinal contractor genes in mouse
      organs during the perinatal period.
AB  - In an attempt to understand the significance of endothelin-1 (ET-1) and
      vasoactive intestinal contractor (VIC)/ET-2 peptides in organs during perinatal
      development, we performed quantitative analysis of ET-1 and VIC gene expression
      in mouse organs obtained from embryos at days 14 and 17 (E-14 and E-17) of
      pregnancy, neonates at days 0, 1, 3 and 7 after birth (N-0, -1, -3 and -7), and
      adult mice (10 weeks old). In intestine, VIC gene expression progressively
      increased between E-14 and N-1 (approximately 10-fold) and then remained constant
      into adulthood. ET-1 gene expression exhibited a one-step increase between E-17
      and N-0, subsequently remaining constant. In lung, a sharp increase in ET-1 mRNA
      level (approximately 10-fold) was noticed between E-14 and N-0. The gene
      expression pattern of VIC, with a peak at N-0, was similar to that of ET-1
      although the expression level of VIC was two to three orders of magnitudes lower
      than that of ET-1. Gene expression patterns of ET-1 and VIC remained nearly
      constant in brain, heart, liver and kidney throughout the period examined.
      Considering that the intestinal and pulmonary gene expression levels of both
      genes reached almost the same level as observed in adult soon after birth, we
      suggest that these peptides may be involved in the emergence and maintenance of
      intestinal and pulmonary functions vital after birth.

PMID- 12193079
TI  - G-protein-coupled receptors in human atherosclerosis: comparison of
      vasoconstrictors (endothelin and thromboxane) with recently de-orphanized
      (urotensin-II, apelin and ghrelin) receptors.
AB  - Endothelin (ET)-1 and thromboxane (Tx) levels are increased in human
      atherosclerosis. One of the aims of this study was to understand how receptors
      for a peptide mediator (ET-1) with a long physiological half life, would differ
      from a lipid mediator (TxA(2)), with a short physiological half life, in human
      coronary artery disease (CAD). Secondly, to determine if receptor protein is
      present in human coronary artery vascular smooth muscle for the recently adopted
      peptide orphan receptors for urotensin-II, apelin and ghrelin. The ET(A) receptor
      subtype predominated in the medial smooth muscle layer of both non-diseased
      coronary artery (NCA) and CAD. However, this subtype was present at relatively
      low density in the proliferated intimal layer of CAD. The ET(B) receptor protein
      was not altered with CAD, compared with NCA. Tx receptor density was
      significantly (P<0.05) increased in both the media and intima of CAD, compared
      with NCA. There was no alteration in receptor density, on the medial smooth
      muscle for urotensin-II and apelin with CAD. Interestingly, receptor density for
      the novel vasodilator peptide ghrelin was significantly (P<0.05) increased
      (approx. 4 fold) with CAD, compared with NCA. The alteration of receptor density
      with disease for Tx and ghrelin provides novel therapeutic targets for the
      treatment of atherosclerosis. In conclusion, while some GPCR are altered, others
      remain unchanged with human atherosclerosis. The increase in vasoconstrictor Tx
      receptor density with disease suggests the importance of Tx receptor antagonism.
      Intriguingly, the increase in receptor density for the novel vasodilator ghrelin,
      identified from post-genomic research, may potentially be beneficial with human
      atherosclerosis.

PMID- 12193080
TI  - Endothelin-1 mRNA and protein in vascular wall cells is increased by reactive
      oxygen species.
AB  - A dysregulated metabolism of oxygen-derived free radicals, nitric oxide and
      endothelin-1(ET-1) in conditions such as hypercholesterolaemia or hypertension
      may promote the development of atherosclerosis. We therefore subjected cultured
      human umbilical vein endothelial cells and coronary artery smooth muscle cells to
      oxidative stress induced by xanthine oxidase or hydrogen peroxide and observed
      alterations in ET-1 metabolism. Incubation with oxygen-derived free radicals
      increased preproET-1 promoter activity, ET-1 mRNA synthesis and big ET-1
      concentrations in both cell types. This interaction of oxidative stress and ET-1
      expression may be relevant in atherogenic conditions such as
      hypercholesterolaemia and hypertension since our data indicate that oxidative
      stress further aggravates the injurious effects attributed to ET-1.

PMID- 12193081
TI  - Acute endothelin(A) receptor antagonism improves coronary artery compliance in
      coronary artery disease patients.
AB  - Endothelin (ET) exerts a tonic, stiffening effect on the common carotid artery in
      rats in vitro. This effect is mediated via the ET(A) receptor. The aim of this
      study was to examine the acute effects of ET(A) receptor antagonism on coronary
      artery compliance in humans. We examined 22 patients with stable angina after
      diagnostic coronary arteriography. Intracoronary BQ-123 (6 micromol), an ET(A)
      receptor antagonist (14 patients), or saline (8 patients), was infused in an
      artery without significant lesion over 20 min. The artery lumen area in the
      proximal arterial segment was measured at end diastole and end systole before and
      after BQ-123 or saline administration using an intravascular ultrasound catheter.
      Calculations were made of absolute (in mm(2)/mmHg x 10(3)) and normalized
      compliance index (in mmHg(-1) x 10(3)). Pulse pressure decreased from 64+/-21 to
      61+/-17 mmHg after BQ-123 administration and increased from 59+/-16 to 68+/-20
      mmHg after saline administration (F=9.54, P=0.006). The respective changes in
      absolute compliance index were from 24+/-18 to 39+/-25 and from 19+/-15 to 14+/
      17 (F=6.43, P=0.02). Normalized compliance index changed from 2.5+/-2.0 to 3.6+/
      2.4 and from 2.7+/-2.6 to 1.6+/-1.8 (F=11.92, P=0.002) respectively, in the two
      groups. Acute ET(A) receptor antagonism improves coronary artery compliance in
      coronary artery disease patients.

PMID- 12193083
TI  - Differential effects of endothelin-1 on isolated working rat hearts before and
      after ischaemia and reperfusion.
AB  - Endothelin (ET) may have both detrimental (reduced coronary flow) and beneficial
      effects (positive inotrope, reduced arrhythmogenesis) following ischaemia. We
      examined the effects of ET on cardiac function during reperfusion following
      prolonged hypothermic cardioplegic arrest in a protocol mimicking cardiac
      transplantation. Isolated working rat hearts were perfused with Krebs buffer to
      which increasing concentrations of ET-1 or sarafotoxin S6c had been added.
      Identical experiments were performed after 4 h of cardioplegic arrest at 4
      degrees C. Under pre-ischaemic conditions ET-1 caused a dose-dependent decrease
      in cardiac function compared with controls. In contrast, following ischaemia low
      doses of ET-1 (10(-10) M) caused a significant and beneficial increase in cardiac
      output (109.1% versus 81.3%), dP/dt i.e. the rate of change of pressure with time
      (94.7% versus 75.6%) and stroke volume (100.3% versus 77.5%) compared with
      controls (P<0.05). At higher doses of ET-1 there was a detrimental effect on
      cardiac output, dP/dt and stroke volume similar to that seen prior to ischaemia.
      Sarafotoxin S6c had no significant effect pre or post ischaemia on any of the
      parameters measured compared with controls (P=not significant). ET-1 at low
      concentrations during reperfusion can improve the recovery of cardiac function
      mediated via ET(A) receptors. ET may play an important physiological role in the
      recovery of cardiac function following prolonged ischaemia.

PMID- 12193082
TI  - ETA receptor antagonists inhibit intimal smooth muscle cell proliferation in
      human vessels.
AB  - We have determined the ability of the endothelin (ET)(A) receptor antagonist,
      PD156707 (CI 1020), to inhibit intimal proliferation in human saphenous veins
      maintained in organ culture. After 28 days in culture, veins exposed to 1 microM
      PD156707 exhibited a significant reduction in intima to intima-plus-media ratio
      (I:I+M ratio) (0.14+/-0.02, n=15) and an increase in lumen area (3.1+/-0.8 mm(2))
      compared with veins cultured without the antagonist (I:I+M, 0.29+/-0.02; lumen
      area, 2.5+/-0.7 mm(2); n=23) but were not significantly different from pre
      cultured controls (I:I+M, 0.15+/-0.02; lumen area, 4.4+/-1.2 mm(2); n=17) (Dunn's
      test for non-parametric multiple comparisons: alpha<0.05). In organ bath
      experiments, ET-1 and 5-hydroxytryptamine constricted pre-cultured control
      vessels with pD(2) values (where pD(2) is defined as the negative logarithm of
      the molar EC(50) value of an agonist) of 8.9+/-0.4 and 7.0+/-0.4 (n=3) and E(max)
      (efficacy) values of 86+/-3% and 71+/-13% (compared with constriction induced by
      KCl) respectively. There was no difference in the responsiveness of veins
      cultured for 14 days to either agonist, indicating that the vessels maintained in
      organ culture remain viable. Crucially, vein segments cultured with 1 microM
      PD156707 (a concentration that antagonized ET-1 responses in pre-cultured control
      vessels) contracted to ET-1 with a potency comparable to that obtained in vessels
      cultured in the absence of the antagonist (pD(2)=8.9+/-0.4 and 8.0+/-0.6
      respectively, n=3) confirming that PD156707 was not toxic to the tissue at the
      concentration used. In conclusion we have shown that the ET(A)-selective
      antagonist, PD156707, completely blocked intimal hyperplasia in human saphenous
      veins in organ culture, suggesting that ET(A) antagonists may be beneficial in
      preventing or delaying saphenous vein graft disease in patients receiving bypass
      grafts for coronary artery disease.

PMID- 12193084
TI  - Coronary responses to endothelin-1 and acetylcholine during partial coronary
      ischaemia and reperfusion in anaesthetized goats.
AB  - To examine coronary reactivity to acetylcholine and endothelin-1 (ET-1) during
      partial ischaemia and reperfusion, flow in the left circumflex coronary artery
      was measured electromagnetically, and coronary partial ischaemia was induced by
      stenosis of this artery in anaesthetized goats. In eight animals not treated with
      N(G)-nitro-l-arginine methyl ester (l-NAME), coronary stenosis reduced coronary
      flow by 45%, mean arterial pressure by 16% and coronary vascular conductance by
      34%. During this ischaemia, coronary vasodilatation to acetylcholine (0.003-0.1
      microg) and sodium nitroprusside (SNP; 1-10 microg) was markedly reduced, and
      coronary vasoconstriction to ET-1 (0.01-0.3 nmol) was attenuated. After 30 min of
      reperfusion, coronary flow, mean arterial pressure and coronary vascular
      conductance remained decreased, and the effects of acetylcholine, SNP and ET-1
      were as in control animals. In six goats treated with N(G)-nitro-l-arginine
      methyl ester, coronary stenosis reduced coronary flow by 26% and coronary
      vascular conductance by 24%, but did not affect mean arterial pressure. During
      this ischaemia, coronary vasodilatation to acetylcholine and SNP was also
      markedly reduced, but vasoconstriction to ET-1 was unaffected. After 30 min of
      reperfusion, coronary flow and coronary vascular conductance remained decreased
      and mean arterial pressure was normal; in addition, the effects of acetylcholine
      were lower, those of SNP were similar and those of ET-1 were higher than in
      control animals. Therefore partial ischaemia reduces the coronary vasodilator
      reserve and blunts coronary vasoconstriction to ET-1, and reperfusion does not
      alter the endothelium-dependent and -independent coronary vasodilatation or
      vasoconstriction to ET-1.

PMID- 12193085
TI  - Pericardial concentrations of adenosine, inosine and hypoxanthine in an
      experimental canine model of spastic ischaemia.
AB  - It has been shown that the adenosine concentration in the pericardial fluid of
      the normal heart is higher by one order of magnitude than that of the venous
      plasma. A further increase in the pericardial adenosine concentration was also
      demonstrated in myocardial ischaemia or hypoxia. It was proposed that pericardial
      nucleoside levels may represent the interstitial concentrations of the adenine
      nucleosides. An experimental model was designed to determine the intrapericardial
      concentrations of adenosine, inosine and hypoxanthine during coronary spasm
      provoked by intracoronary administration of endothelin-1 (ET-1; 0.08+/-0.02
      nmol/g of myocardial tissue). In the in situ dog heart (n=10), adenosine, inosine
      and hypoxanthine concentrations were determined by HPLC in fluid samples
      collected from the closed pericardial sac before and after ET-1 administration,
      and from the systemic arterial blood. Systemic blood pressure, heart rate and
      standard ECG were registered continuously. We found that the nucleoside
      concentrations in the infusate samples increased significantly during coronary
      spasm [adenosine, 1.49+/-0.44 compared with 0.37+/-0.07 microM (P<0.05); inosine,
      27.43+/-11.51 compared with 0.47+/-0.11 microM (P<0.05); hypoxanthine, 21.17+/
      6.49 compared with 4.91+/-1.24 microM (P<0.05)], while a significant decrease in
      blood pressure and an elevation in ECG ST segments were observed. The levels of
      the purine metabolites did not change in the systemic blood. The data indicate
      that changes in adenine nucleoside levels measured in pericardial infusate
      samples reflect activation of coronary metabolic adaptation in this model of
      spastic ischaemia, and that pericardial nucleoside levels may characterize
      alterations in interstitial adenine nucleoside concentrations.

PMID- 12193086
TI  - Endothelin-1-induced elevations in purine metabolite concentrations --
      autoregulatory protection in the canine pericardium?
AB  - Pericardial fluid accumulates the cardioprotective purine metabolites, as well as
      the endogenous vasoconstrictor agent endothelin-1 (ET-1). The aim of the present
      study was to characterize the pericardial concentrations of the purine
      metabolites adenosine, inosine and hypoxanthine before and after intrapericardial
      administration of ET-1 to the in situ heart. The closed pericardial sac of
      anaesthetized dogs (n=9) was cannulated for ET-1 administration and for obtaining
      native pericardial fluid and control pericardial infusate samples (C1 and C2), as
      well as consecutive pericardial infusate samples (samples I, II and III) obtained
      15 min after intrapericardial administration of 150 pmol/kg ET-1. In an
      additional five dogs, using the same protocol, ventricular epicardial and
      endocardial monophasic action potential recordings were performed to assess local
      ischaemic electrophysiological changes. Significant elevations of pericardial
      purine metabolite concentrations (measured by HPLC) were found in sample II
      compared with sample C2: adenosine, 4.5+/-1.7 compared with 0.5+/-0.1 microM
      (P<0.05); inosine, 18.3+/-2.8 compared with 0.9+/-0.2 microM (P<0.001);
      hypoxanthine, 38.1+/-8.0 compared with 13.4+/-2.6 microM (P<0.01). Systemic blood
      pressure, left ventricular pressure and contractility, and systemic plasma levels
      of the purine metabolites remained unchanged during the ET-1 effect, while
      significant ECG ST elevations (ST(max) 0.68+/-0.01 mV; P<0.001) were observed. In
      the five dogs analysed electrophysiologically, the left ventricular epicardial
      monophasic action potential duration and upstroke velocity decreased
      significantly at time point II compared with C2, while the endocardial monophasic
      action potential duration and upstroke velocity did not show ischaemia-related
      changes. The results suggest that intrapericardial administration of ET-1 induces
      subepicardial ischaemia, with parallel activation of coronary metabolic adaptive
      and cardiac self-protective mechanisms in the epimyocardial layer of the heart.

PMID- 12193087
TI  - Up-regulation of endothelin-converting-enzyme mRNA expression following
      cardioplegic arrest.
AB  - Endothelin-1 (ET-1) is believed to play an important role in cardiac
      ischaemia/reperfusion injury. ET-1 is synthesized from preproET-1 by the action
      of ET-converting enzyme (ECE). It is unclear to what extent the ET system is
      activated following prolonged ischaemia. In this study we used a model mimicking
      the conditions of the donor heart during transplantation. Isolated rat hearts
      perfused with Krebs-Henseleit buffer were subjected to 30 min of normothermic
      perfusion, then 4 h of cardioplegic arrest at 4 degrees C with St Thomas'
      Hospital solution, followed by reperfusion for 2 h. Hearts were freeze-clamped at
      different time points during the protocol. Using quantitative reverse
      transcription-PCR, relative levels of ET-1 and ECE mRNA expression were measured
      and compared with a housekeeping gene (ribosomal protein L32). During reperfusion
      there was a consistent decrease in coronary flow to approx. 85-90% of pre
      ischaemic flow. There was no significant alteration in preproET-1 mRNA expression
      during 2 h of reperfusion. However, ECE mRNA expression was increased by 77.5% at
      1 h and by 74.6% at 2 h following ischaemia compared with pre-ischaemic values
      (P<0.05). Thus we conclude that ECE mRNA expression is increased following
      prolonged hypothermic cardioplegic arrest. Elevations in the expression of this
      enzyme may help to explain the role of the ET system in the pathogenesis of
      ischaemia/reperfusion injury following cardiac surgery and transplantation.

PMID- 12193088
TI  - Enhancement of glycolysis in cardiomyocytes elevates endothelin-1 expression
      through the transcriptional factor hypoxia-inducible factor-1 alpha.
AB  - We investigated whether the type of energy metabolism directly affects cardiac
      gene expression. During development, the heart switches from glycolysis to fatty
      acid beta-oxidation in vivo, as demonstrated by the developmental switching of
      the major isoform of myosin heavy chain (MHC) from beta to alpha. However, the
      beta-MHC isoform predominates in monocrotaline-induced pulmonary hypertension, a
      model of right ventricular hypertrophy in vivo. Cultured cardiomyocytes showed a
      predominance of beta-MHC expression over that of alpha-MHC, the same pattern as
      in the hypertrophied heart, suggesting that the in vitro condition itself causes
      the energy metabolism of cardiomyocytes to be switched to glycolysis. Electrical
      stimulation of cultured cardiomyocytes decreased the expression of glyceraldehyde
      3-phosphate dehydrogenase (GAPDH) and hypoxia-inducible factor-1 alpha (HIF-1
      alpha), but not that of peroxisome-proliferator-activated receptor-gamma co
      activator, suggesting that electrical stimulation suppresses the glycolytic
      system. Furthermore, a higher oxygen content (50%) decreased drastically the
      expression of GAPDH, HIF-1 alpha and endothelin-1 (ET-1), and increased
      [(3)H]palmitate uptake. These findings indicate that the intrinsic energy
      metabolic system in cultured cardiomyocytes in vitro is predominantly glycolysis,
      and that the gene expression of cardiac ET-1 parallels the state of the
      glycolytic system. An antisense oligonucleotide against HIF-1 alpha greatly
      decreased the gene expression of ET-1 and GAPDH, suggesting that cardiac ET-1
      gene expression is regulated by cardiac energy metabolism through HIF-1 alpha. In
      conclusion, it is suggested that the pattern of gene expression of ET-1 reflects
      the level of the glycolytic system in cardiomyocytes, and that enhanced
      glycolysis regulates the cardiac gene expression of ET-1 via HIF-1 alpha.

PMID- 12193090
TI  - Expressed monophasic action potential alternans before the onset of ventricular
      arrhythmias induced by intracoronary bolus administration of endothelin-1 in
      dogs.
AB  - We showed previously a direct arrhythmogenic effect of the intracoronary infusion
      of endothelin-1 (ET-1). We aimed to examine the electrophysiological effects of
      intracoronary bolus administration of ET-1 using monophasic action potential
      (MAP) recordings. Eight mongrel dogs received boli of ET-1 (1 and 2 nmol) into
      the left anterior descending coronary artery. These intracoronary ET-1 boli
      rapidly caused a marked decrease in coronary blood flow (1 nmol, 78+/-7%; 2 nmol,
      89+/-7%). Ischaemic changes of MAP morphology, a decrease in upstroke velocity
      (baseline, 1.78+/-0.2 V/s; 1 nmol, 0.95+/-0.18 V/s; 2 nmol, 0.45+/-0.21 V/s;
      P<0.01) and a decrease in MAP duration at 90% repolarization (MAPD(90)) [1 nmol,
      from 191+/-3 to 176+/-5 ms (P<0.05); 2 nmol, from 212+/-4 to 180+/-8 ms (P<0.05)]
      occurred after ET-1 bolus administration. However, at 7-10 min after the 1 nmol
      bolus, a significant increase in MAPD(90) was observed (10 min, in the left
      ventricular anterior epicardial region: from 191+/-3 to 206+/-6 ms; P<0.05). The
      incidence of ventricular arrhythmias was as follows: after the 1 nmol ET-1 bolus:
      ventricular tachycardia, 3/8 animals; ventricular fibrillation, 1/8; after the 2
      nmol ET-1 bolus: ventricular tachycardia, 5/7; ventricular fibrillation, 5/7. MAP
      alternans was present in each animal (1 nmol, 18.2+/-5.8%; 2 nmol, 10.8+/-2.5%).
      Thus electrophysiological and coronary blood flow changes indicate the
      predominance of an ischaemic arrhythmogenic effect of the bolus administration of
      ET-1 (shortening of action potential duration; appearance of MAP alternans),
      whereas the observed delayed prolongation of MAPD(90) suggests a direct
      arrhythmogenic effect of ET-1. The expressed MAP alternans could have a
      pathogenic role in the onset of ventricular arrhythmias induced by an
      intracoronary bolus of ET-1.

PMID- 12193089
TI  - ET(A) receptor blockade improves post-ischaemic functional recovery in
      'hibernating' rat myocardium.
AB  - Endothelin-1 (ET-1) is a potent vasoconstrictor, and ET(A) receptors mainly
      mediate this effect. Elevated plasma levels of ET-1 are observed in patients with
      coronary heart disease. The release of this peptide from the damaged endothelium
      may play a role in the initiation and maintenance of myocardial ischaemia. This
      study examines the ET(A) receptor-mediated role of endogenous ET-1 in post
      ischaemic myocardial function after prolonged hypoperfusion in normal non-failing
      hearts. In an isolated rat heart model for short-term myocardial hibernation,
      left ventricular functional recovery after 3 h of hypoperfusion (15% of pre
      ischaemic flow) followed by 2 h of reperfusion was determined. Under steady-state
      conditions, coronary flow, left ventricular pressure (LVP) and dP/dt(max) were
      measured in the isovolumically beating heart. Additionally, the maximal inotropic
      response (LVP and dP/dt(max)) to calcium stimulation was determined. To study the
      role of ET(A) receptors under these pathophysiological conditions, one group was
      treated with the ET(A) antagonist BQ 610 (0.8 micromol/l) during hypoperfusion,
      and compared with a control group which received a saline infusion during
      hypoperfusion. Reperfusion for 2 h after 3 h of hypoperfusion resulted in partial
      functional recovery in both groups. Post-ischaemic recovery was significantly
      better in the hearts that were treated with the ET(A) antagonist BQ 610 during
      hypoperfusion (LVP, +19.5% compared with control; dP/dt(max), +13.7% compared
      with control). The inotropic response to calcium was nearly normalized after
      ET(A) blockade. Thus the normal non-failing myocardium profits from ET(A)
      receptor blockade during a prolonged period of hypoperfusion, resulting in
      significantly better post-ischaemic recovery of myocardial function.

PMID- 12193091
TI  - The ET(A) receptor antagonist LU 135252 has no electrophysiological or anti
      arrhythmic effects during myocardial ischaemia/reperfusion in dogs.
AB  - The anti-arrhythmic effects of ET(A) receptor antagonists during myocardial
      ischaemia and reperfusion remain controversial. Moreover, the
      electrophysiological mechanism has not yet been identified. The aim of this study
      was to investigate the potential anti-arrhythmic and electrophysiological effects
      of the ET(A) receptor antagonist LU 135252 (LU) during myocardial ischaemia and
      reperfusion in a canine model. A bolus of LU (1 mg/kg; n=10) or saline (control;
      n=10) was injected into the left anterior descending coronary artery before
      ligation of this vessel for 30 min, which was followed by a 90-min reperfusion
      period. LU bolus administration (0.5 mg/kg) was repeated every 30 min. There were
      no differences in mean arterial blood pressure or coronary blood flow between the
      two groups. The determined left ventricular ischaemic mass was 25.5+/-1.8% and
      27.8+/-2.2% of the total left ventricular mass in the control and LU groups
      respectively. The total incidence of ventricular fibrillation during ischaemia
      and reperfusion was 40% in the control and 50% in the LU group (not significantly
      different). The incidence of non-sustained and sustained ventricular tachycardias
      during ischaemia, reperfusion and over the whole period (ischaemia plus
      reperfusion) in the control group was 50%, 50% and 70% respectively, and that in
      the LU group was 80%, 70% and 100% respectively (no significant differences
      between groups). The number of ventricular premature beats was not decreased by
      LU during either ischaemia or reperfusion [median (25th-75th percentile):
      ischaemia, 20 (13-37) and 56 (32-130) for LU and control groups respectively;
      reperfusion, 15 (2-21) and 39 (7-74) respectively; ischaemia+reperfusion, 16 (4
      35) and 43 (10-82) respectively; no significant differences between groups].
      During ischaemia, the monophasic action potential duration at 90% repolarization
      (MAPD(90)) decreased significantly, while during reperfusion a significant
      prolongation of MAPD(90) was observed in the left anterior descending region that
      was similar in the two groups. In conclusion, LU did not affect repolarization
      changes and did not have anti-arrhythmic effects during either ischaemia or
      reperfusion in this model.

PMID- 12193092
TI  - Involvement of endothelin-1 in acute ischaemic arrhythmias in cats and rats.
AB  - This study aims to investigate the role of endothelin-1 (ET-1) in the genesis of
      acute ischaemic arrhythmias. In anaesthetized cats and rats receiving continuous
      monitor of electrocardiogram and arterial blood pressure, the ischaemic
      arrhythmias during 60-min myocardial ischaemia elicited by the occlusion of the
      left anterior descending coronary artery (LAD) were analysed. To prevent the
      putative arrhythmic effects of endogenous ET-1, ET(A) receptor antagonist BQ610
      (1.5-6.0 nmol/kg) was intracoronary injected just before LAD occlusion in cats,
      and preproET-1 mRNA antisense oligodeoxynucleotide (AS-ODN; 30-90 nmol/kg) was
      intravenously injected 2 h before LAD occlusion in rats. The results showed that
      BQ610 dose-dependently decreased the incidences of ventricular tachycardia (VT)
      and ventricular fibrillation (VF), and the numbers of ventricular ectopic beats
      (VEBs). At the dose of 6.0 nmol/kg, the incidence of VT decreased significantly
      from 33.3% in normal saline (NS) control group to zero (P<0.01), and total VEBs
      decreased significantly from 831+/-162 to 158+/-51 (P<0.05). In rats receiving ET
      1 AS-ODN, plasma ET-1 decreased significantly after 2 h, and remained stable at
      30 min of LAD occlusion. However, in rats receiving the control, NS or sense ODN,
      plasma ET-1 remained unchanged after administration, but increased significantly
      during LAD occlusion. The ischaemic arrhythmias were dose-dependently suppressed
      in the presence of ET-1 AS-ODN. At the dose of 90 nmol/kg, the incidence of VT
      decreased significantly from 100% in both the control groups to 30%. The numbers
      of single VEBs, consecutive VEBs, VT and total VEBs were also significantly
      decreased, from 60+/-15 in NS group to 19+/-12, 11+/-3 to 2+/-2, 155+/-41 to 11+/
      11, and 239+/-49 to 35+/-25 respectively. In the present cat and rat models of
      coronary artery occlusion, antagonism of either ET(A) receptors or endogenous ET
      1 synthesis prevented the ischaemic arrhythmias, indicating that ET-1 is possibly
      an important promotive factor in the genesis of acute ischaemic arrhythmias.

PMID- 12193093
TI  - Effects of implantable cardioverter defibrillator implantation and shock
      application on serum endothelin-1 and big-endothelin levels.
AB  - The incidence of ventricular tachyarrhythmias in the early post-operative period
      following implantable cardioverter-defibrillator (ICD) implantation is relatively
      high compared with that in control periods. Since endothelin-1 (ET-1) has been
      proven to be an endogenous arrhythmogenic substance, we investigated the changes
      in serum ET-1 and big-ET levels in patients undergoing ICD implantation. Serum
      concentrations of ET-1 and big-ET were measured in 14 patients with various heart
      diseases before the operation, as well as 1 min and 1 h after the last shock
      therapy. Big-ET levels and the sum of ET-1 and big-ET levels were unchanged
      immediately after the operation, but had increased significantly by 1 h after
      implantation (before, 1.57+/-0.61 pmol/l; 1 min, 1.86+/-0.87 pmol/l; 1 h, 4.29+/
      1.65 pmol/l for big-ET; before, 3.44+/-1.07 pmol/l; 1 min, 3.79+/-1.29 pmol/l; 1
      h, 6.36+/-2.03 pmol/l for big-ET+ET-1). There was a significant correlation
      between left ventricular ejection fraction and big-ET level measured 1 h after
      the last shock delivery (r=-0.542, P<0.05). We conclude that the increased big-ET
      level observed 1 h after the last induction and shock therapy of ventricular
      fibrillation might have a pathophysiological role in the increased incidence of
      post-operative spontaneous ventricular arrhythmias.

PMID- 12193094
TI  - Increased expression of endothelin-converting enzyme-1 in failing human
      myocardium.
AB  - Endothelin-1 (ET-1) is considered to be involved in the development and
      progression of heart failure. Therefore, we analysed the expression of endothelin
      converting enzyme-1 (ECE-1), endothelin receptors A (ET(A)) and B (ET(B)) mRNAs
      by standard-calibrated, competitive reverse transcriptase-PCR using an internal
      deleted in vitro-transcribed cRNA standard. ET-1 peptide levels were measured
      using isoform-specific rabbit antibodies against synthetic ET-1. mRNA and protein
      expression was determined in the right atrial myocardium of New York Heart
      Association class I patients and class IV patients undergoing aorto-coronary
      bypass surgery. ECE-1 mRNA was upregulated in failing atrial myocardium.
      Furthermore, ET-1 peptide levels were increased in failing atrial myocardium.
      Atrial ET(A) mRNA expression was not changed, while ET(B) mRNA was downregulated
      in the failing atrial myocardium. Our results support an upregulation of ET-1
      synthesis by induction of ECE-1 in failing atrial myocardium. Pharmacological
      inhibition of augmented ECE-1 expression might provide a new therapeutic
      perspective in the treatment of heart failure.

PMID- 12193096
TI  - Effects of endothelin receptors ET(A) and ET(B) blockade on renal haemodynamics
      in normal rats and in rats with experimental congestive heart failure.
AB  - The present study examined the effects of two highly selective endothelin-1 (ET
      1) receptor antagonists, ABT-627 (ET(A) blocker) and A-192621 (ET(B) blocker), on
      the systemic and renal haemodynamic effects of ET-1 in normal rats and in rats
      with experimental congestive heart failure (CHF) produced by aortocaval fistula.
      Intravenous injection of ET-1 (1.0 nmol x kg(-1) of body weight) to anaesthetized
      normal rats produced sustained decreases in renal blood flow (RBF) (assessed by
      ultrasonic flowmetry) and glomerular filtration rate (GFR), and significant
      increases in renal vascular resistance (RVR) and mean arterial pressure (MAP).
      Pretreatment with ABT-627 (1 mg x h(-1) x kg(-1) of body weight) abolished the
      pressor response to ET-1 without affecting the depressor phase, and significantly
      impaired the renal vasoconstriction. The systemic and renal vasoconstrictive
      effects of ET-1 in normal rats were significantly augmented by pretreatment with
      3.0 mg x h(-1) x kg(-1) of A-192621. Baseline RBF and GFR in rats with CHF were
      reduced significantly compared with control rats, whereas RVR was elevated. The
      hypertensive effect of ET-1 was attenuated in rats with CHF. In the presence of
      ET(A) blockade, the pressor response to ET-1 was completely abolished in CHF
      rats. Furthermore, pretreatment with ABT-627 enhanced the recovery from ET-1-
      dependent vasoconstriction and remarkably reversed the ET-1-induced
      hypofiltration. Blockade of ET(B) receptors in rats with CHF further exposed the
      exaggerated ET-1-induced renal vasoconstriction. Our data demonstrate that
      experimental CHF is associated with altered responsiveness to ET(A)- and ET(B)
      mediated systemic and renal effects of ET-1. Furthermore, in CHF, as in control
      rats, the ET(B)-mediated vasodilatory response may serve as an important
      compensatory counterbalance to the adverse ET(A)-mediated effects.

PMID- 12193095
TI  - Endothelin stimulates an endogenous nitric oxide synthase inhibitor, asymmetric
      dimethylarginine, in experimental heart failure.
AB  - Congestive heart failure (CHF) is characterized by increased peripheral vascular
      resistance. Endothelin-1 (ET-1), a potent endothelium-derived vasoconstrictor, is
      present at increased concentrations in the plasma and contributes to the
      regulation of vascular tone in CHF. An endothelium-derived relaxing factor,
      nitric oxide (NO), also regulates vascular tone, but endothelium-dependent NO
      mediated vasodilation is blunted in CHF. An endogenous NO synthase inhibitor,
      asymmetric dimethylarginine (ADMA), which inhibits NO production and endothelium
      dependent relaxation, is present at increased levels in the plasma and plays a
      role in impaired endothelial function in CHF. However, at present, the
      relationship between ET-1 and impaired vascular relaxation in CHF is not well
      known. We hypothesized that ET-1 inhibits NO-mediated vasodilation via increased
      ADMA production in CHF, and that an endothelin receptor antagonist can prevent
      this increase in plasma ADMA levels. In the present study, we first examined
      whether circulating ADMA levels were increased in a dog model of CHF induced by 3
      weeks of rapid ventricular pacing (n=5; 270 beats/min) compared with normal dogs
      (n=5). After 3 weeks of pacing, cardiac output had decreased significantly
      (1.56+/-0.16 compared with 2.93+/-0.25 litres/min; P<0.01) and systemic vascular
      resistance had increased (4653+/-374 compared with 3227+/-396 dyn.s.cm(-5);
      P<0.01) in dogs with CHF compared with normal dogs. Plasma levels of both ET-1
      (4.95+/-0.83 compared with 2.12+/-0.39 pg/ml; P<0.05) and ADMA (3.27+/-0.49
      compared with 1.91+/-0.25 nmol/ml; P<0.05) were significantly increased in CHF
      dogs. A significant positive correlation was observed between plasma ET-1 and
      ADMA levels (r=0.72, P<0.05). Secondly, we chronically administered an ET(A)
      receptor antagonist, TA-0201 (0.3 mg/kg; n=5), to paced CHF dogs. Drug
      administration started on day 8 of pacing and continued throughout the
      experiment. TA-0201 significantly increased cardiac output (2.58+/-0.24
      litres/min; P<0.01) and suppressed the increases in plasma ADMA levels and
      systemic vascular resistance (2.36+/-0.30 nmol/ml and 2423+/-188 dyn.s.cm(-5)
      respectively; P<0.05 for each) compared with CHF dogs without TA-0201 treatment.
      In conclusion, ET-1 contributes to the regulation of vascular tone due, in part,
      to increased levels of an endogenous NO synthase inhibitor in CHF, and an ET(A)
      receptor antagonist can prevent the inhibition of NO production and the increased
      peripheral vascular resistance observed in CHF.

PMID- 12193097
TI  - Treatment with darusentan over 21 days improved cGMP generation in patients with
      chronic heart failure.
AB  - In heart failure, the cGMP to natriuretic peptide ratio is decreased and infusion
      of atrial natriuretic peptide (ANP) induces less cGMP generation. The ratio of
      the second messenger cGMP to plasma concentrations of ANP or brain natriuretic
      peptide (BNP) correlates with the effectiveness of natriuretic peptides. It was
      investigated whether blockade of the ET(A) receptor might improve the cGMP:NP
      ratio in heart failure. Patients with chronic heart failure (n=142; mean age=57
      years) received oral treatment with the ET(A) antagonist darusentan (either 30,
      100, 300 mg/day or placebo) on top of standard therapy over a period of 21 days
      in a randomized, double-blind, placebo-controlled, multicentre study. Plasma
      concentrations of ANP, BNP and cGMP were determined before randomization and
      after 21 days of treatment. In parallel with decreased pulmonary and systemic
      vascular resistance, 3 weeks of oral treatment with the ET(A) receptor antagonist
      darusentan reduced BNP plasma levels and increased the cGMP:BNP ratio
      significantly. The improved cGMP:BNP ratio might reflect the ability of chronic
      ET(A) receptor blockade to facilitate the generation of the second messenger
      cGMP, which points towards a favourable modulation of the natriuretic peptide
      effector system, in addition to haemodynamic improvement in heart failure
      patients.

PMID- 12193098
TI  - Chronic effects of an endothelin-converting enzyme inhibitor on cardiorenal and
      hormonal function in heart failure.
AB  - Endothelin (ET)-converting enzyme (ECE) is a rate-limiting step in ET-1
      generation, and its expression and activity are increased significantly with the
      development of congestive heart failure (CHF). The selective enzymic inhibition
      of ET-1 formation thus seems to be a very important target in the prevention of
      CHF. We evaluated the chronic effects of a specific ECE inhibitor, FR901533 (0.3
      mg x kg(-1) x h(-1), n=5) on cardiac, hormonal, and body fluid balance in dogs
      with CHF induced by rapid right ventricular pacing (270 beats/min, 22 days).
      Vehicle dogs were given placebo (n=5). Despite no significant difference in blood
      pressure, FR901533 decreased pulmonary capillary wedge pressure and increased
      cardiac output compared with the vehicle. FR901533 prevented the reduction of
      urine flow rate and urinary sodium excretion in association with an increase in
      the glomerular filtration rate and renal plasma flow compared with the vehicle.
      FR901533 also suppressed significantly the elevation of plasma atrial natriuretic
      peptide and aldosterone levels which is an established prognostic factor in CHF.
      These results indicate that the role of ECE in CHF is important and that chronic
      ECE inhibition could possess therapeutic potential in the treatment of CHF not
      only on haemodynamics but also in the prevention of fluid retention.

PMID- 12193099
TI  - Chronic administration of phosphodiesterase type 5 inhibitor suppresses renal
      production of endothelin-1 in dogs with congestive heart failure.
AB  - Endothelin-1 (ET-1) and atrial natriuretic peptide (ANP) play important roles in
      the regulation of body fluid balance in congestive heart failure (CHF). Renal
      production of ET-1 increases in CHF and it is a significant independent predictor
      of sodium excretion. ANP inhibits the ET system through cGMP, a second messenger
      of ANP. However, in severe CHF, plasma cGMP levels reached a plateau despite the
      activation of ANP secretion. Thus, ANP does not seem to sufficiently oppose
      exaggerated ET-1 actions in severe CHF, partially due to the accelerated
      degradation of cGMP, through phosphodiesterase type 5 (PDE5). We examined the
      chronic effects of a PDE5 inhibitor, T-1032 (1 mg/kg per day, n=5), on renal
      function and renal production of ET-1 in dogs with CHF induced by rapid
      ventricular pacing (270 beats/min). Vehicle dogs were given a placebo (n=5) and
      normal dogs (n=5) served as normal controls without pacing. In this
      experimentally produced CHF, plasma levels of ET-1, ANP and cGMP were elevated
      and renal production of cGMP was increased compared with the normal group,
      associated with increases in renal expression of preproET-1 mRNA and the number
      of ET-1-positive cells in glomeruli. In the T-1032 group, systemic and renal
      production of cGMP were further increased compared with the vehicle group despite
      no significant difference in plasma ANP levels between the two groups.
      Subsequently, the agent significantly improved urine flow rate, sodium excretion
      rate and glomerular filtration rate (GFR) associated with reductions in renal
      expression of preproET-1 mRNA and the number of ET-1-positive cells compared with
      the vehicle group. Moreover, there was a significant negative correlation between
      the number of ET-1-positive cells and GFR (r=-0.802 and P<0.001 respectively).
      Our results indicate that chronic PDE5 inhibition ameliorates the antagonistic
      relationship between renal ANP and ET-1 through the cGMP pathway, subsequently
      preventing renal dysfunction during the progression of CHF.

PMID- 12193100
TI  - Role of cardiac myocyte-derived endothelin-1 in chagasic cardiomyopathy:
      molecular genetic evidence.
AB  - Trypanosoma cruzi is the aetiological agent of Chagas' disease, an important
      cause of chronic cardiomyopathy. We previously demonstrated a role for endothelin
      1 (ET-1) in the pathogenesis of chagasic heart disease. In order to explore
      further the significance of ET-1 in chagasic heart disease, we infected ET-1
      (flox/flox); alpha-MHC-Cre(+) (ET-1KO) mice, in which the ET-1 gene has been
      deleted from cardiac myocytes, with 10(4) T. cruzi (Brazil strain)
      trypomastigotes. As controls, we used ET-1 (flox/flox);Cre(-) (FLOX) and
      C57BL/6x129sv (WT) mice. All mice survived and were evaluated 150-160 days post
      infection. Cardiac magnetic resonance imaging revealed a significant increase in
      right ventricular internal diameter in all infected animals except ET-1KO mice
      (control WT, 1.6+/-0.10 mm; infected WT, 2.8+/-0.15 mm; control FLOX, 2.04+/-0.02
      mm; infected FLOX, 2.76+/-0.28 mm). There was no significant difference in right
      ventricular internal diameter between infected and uninfected ET-1KO mice
      (control ET-1KO, 1.83+/-0.11 mm; infected ET-1KO, 2.14+/-0.20 mm). In another
      series of experiments, transthoracic echocardiography was performed on uninfected
      as well as infected ET-1KO mice, and uninfected and infected FLOX mice. Both
      infected groups had an increased left ventricular end-diastolic diameter and
      reduced fractional shortening. In addition, relative wall thickness was also
      decreased in infected animals. However, the magnitude of these changes was less
      in infected ET-1KO mice. These data provide further support for a role for ET-1
      in the pathogenesis of chronic chagasic heart disease, and indicate that cardiac
      myocytes are an important source of ET-1 in this disease.

PMID- 12193101
TI  - Phosphoramidon treatment improves the consequences of chagasic heart disease in
      mice.
AB  - Chagas' disease, caused by the protozoan parasite Trypanosoma cruzi, is an
      important cause of cardiomyopathy. Microvascular spasm and matrix dissolution,
      modulated by endothelin-1 (ET-1), is implicated in the pathogenesis of chagasic
      heart disease. To further elucidate the role of ET-1 in murine chagasic heart
      disease, C57BL/6 x 129sv mice were infected with T. cruzi (10(3) trypomastigotes
      of the Brazil strain). These mice are resistant to death during the acute phase
      but progress to chronic cardiomyopathy. Infected mice were compared with infected
      mice treated with phosphoramidon, a non-specific metalloprotease inhibitor that
      is also a potent inhibitor of endothelin-converting enzyme, at a dose of 10
      mg/kg. Mice were treated with phosphoramidon for the initial 15 days post
      infection (PI). All mice were evaluated 200 days PI. Examination of infected,
      untreated mice revealed marked inflammation, vasculitis and fibrosis. The hearts
      of infected treated mice had significantly less pathology. Cardiac magnetic
      resonance imaging (MRI) revealed that right ventricular internal diameter (RVID)
      was significantly greater (P<0.05) in the infected untreated group (2.9+/-0.22
      mm) as compared with the infected treated group (1.73+/-0.35 mm). In another
      experiment phosphoramidon treatment was also tested in CD1 mice, which have a
      high mortality during the acute phase of infection with 5 x 10(4) trypomastigotes
      of the Brazil strain. One group of CD1 mice was untreated while the other group
      received phosphoramidon for the initial 15 days PI. The mortality rate in
      untreated mice was 70% by day 35 PI, while all treated infected mice lived. The
      parasitemia in both groups was similar. The cardiac pathology was more severe in
      untreated mice. MRI revealed the RVID to be significantly greater in the
      untreated infected group as compared with the phosphoramidon-treated infected
      mice (2.74+/-0.03 mm versus 1.64+/-0.4 mm P<0.05). Transthoracic echocardiography
      revealed that the percentage fractional shortening was reduced in infected CD1
      mice but not in those infected mice treated with phosphoramidon. There was no
      effect of phosphoramidon in uninfected mice. Phosphoramidon (100 microg/ml) had
      no effect on parasites in vitro. These data are consistent with the hypothesis
      that ET-1 contributes to the pathogenesis of murine chagasic cardiomyopathy and
      suggests that interventions targeting ET-1 would improve the outcome in chagasic
      heart disease.

PMID- 12193102
TI  - Role of endothelin-1 in the development of a special type of cardiomyopathy.
AB  - The role of endothelin-1 (ET-1) in certain pathological states is still unclear.
      We have investigated the effect of anthracyclines (maximum dose, 450 mg/m(2) of
      body surface) on left ventricular systolic and diastolic function and how it
      influences the level of plasma ET-1 in 21 patients (12 female and nine male) with
      Hodgkin and non-Hodgkin lymphoma. We also studied the association between plasma
      ET-1 concentration and echocardiographic parameters. Serum ET-1 was measured by
      ELISA. Left ventricular function was analysed by echocardiography: ejection
      fraction (EF), velocity-time integral, E- and A-waves, E:A ratio, deceleration
      time (DT) and Doppler index were all measured. Statistical analysis was made by
      the Wilcoxon rank test. EF and serum ET-1 level decreased significantly (EF,
      56.29+/-5.0% to 48.57+/-5.9%, P<0.0001; ET-1, 6.45+/-4.0 pg/ml to 2.9+/-1.0
      pg/ml, P<0.0001). DT increased significantly (179.8+/-47.8 ms to 215.5+/-66.7 ms,
      P<0.01) after anthracycline therapy. There was no difference in other
      echocardiographic parameters before and after therapy. The decrease in serum ET-1
      concentration might be a result of anthracycline's direct cytotoxic effect and
      the decreasing level of ET-1 can play a role in the reduction of EF. However,
      more studies are needed to evaluate the presence and severity of endothelial
      damage.

PMID- 12193103
TI  - Influence of endothelin receptor antagonists on myocardial protein kinase C
      isoforms in uraemic cardiomyopathy.
AB  - Increased endothelin-1 (ET-1) levels were found in patients with chronic renal
      failure and these correlate with the severity of renal failure. Increased
      mortality due to cardiovascular problems is observed in patients with elevated ET
      1 concentrations. The aim of this study was to find out the influence of ET-1 and
      ET receptor antagonists on myocardial protein kinase C (PKC) regulation in
      uraemic cardiomyopathy. Male rats were subtotally nephrectomized and treated with
      an ET(A)-receptor antagonist (30 mg x kg(-1) x day(-1), LU302146) or an ET(AB)
      receptor antagonist (30 mg x kg(-1) x day(-1), LU302872) for 12 weeks. One group
      was left untreated (SNX) and one group was sham-operated (sham). Systolic blood
      pressure, myocardial weight and the changes of the protein kinase C isoforms in
      the heart were determined. PKC isoforms alpha and delta were investigated by
      Western blot analysis using specific antibodies. In the SNX group, systolic blood
      pressure rose to 154+/-5 mmHg after 12 weeks. The ET(A) receptor antagonist
      prevented this increase in blood pressure, but ET(AB) antagonism did not. Left
      ventricular weight increased in SNX; this increase was inhibited by the ET(A)
      receptor antagonist. In comparison with the sham group, PKC isoform alpha
      increased by 19% in SNX animals. When the SNX animals were treated with ET(A) or
      ET(AB) antagonists, PKC isoform alpha levels decreased by 31%. PKC isoform delta
      levels decreased by 35% in SNX animals. Treatment with both ET(A) or ET(AB)
      antagonists increased PKC isoform delta levels to normal. In the myocardium of
      uraemic rats PKC isoforms are differentially regulated with an increase in alpha
      isoform but a decrease in delta isoform. ET receptor blockers normalize these PKC
      isoforms.

PMID- 12193104
TI  - Endothelin B receptors located on the endothelium provide cardiovascular
      protection in the hamster.
AB  - Endothelins (ETs) act through two receptors, namely ET(A) and ET(B). In the
      cardiovascular system, the activation of both receptors leads to
      vasoconstriction. However, ET(B) receptors also mediate endothelium-dependent
      vasodilatation and clearance of plasma ET-1. With regard to these latter
      properties, we wanted to assess the contribution of ET(B) receptors and the
      effects of selective and mixed ET receptor blockade on vascular tone in control
      Syrian Golden hamsters and in Bio 14.6 cardiomyopathic hamsters after bolus
      injection of ET-1 and IRL-1620, a selective ET(B) agonist. In 12-week-old
      anaesthetized control hamsters, ET-1 (0.5 nmol/kg) induced a sustained pressor
      response which was only partly reduced by the selective ET(A) receptor antagonist
      BQ-123, suggesting a contribution of ET(B) receptor activation to the
      vasoconstrictive effects of ET-1. This was confirmed by injection of the
      selective ET(B) receptor agonist IRL-1620 (1 nmol/kg). However, the pressor
      response to this agonist was always preceded by a transient vasodilatation,
      indicating activation of endothelium-located ET(B) receptors. When the selective
      ET(B) receptor antagonist BQ-788 was administered, the hypotensive phase
      following IRL-1620 injection was abolished. Interestingly, BQ-788 or a mixture of
      BQ-788 and BQ-123 significantly potentiated the pressor responses to ET-1. In 12
      week-old Bio 14.6 cardiomyopathic hamsters, ET-1 and IRL-1620 induced
      haemodynamic responses similar to those observed in control hamsters, although
      the IRL-1620-induced pressor increase was lower. No difference in cardiac prepro
      ET-1 mRNA expression was observed between the two strains of hamsters. In
      conclusion, we suggest that endothelium-located ET(B) receptors are involved in
      the physiological antagonism of ET-dependent protracted pressor effects, and thus
      may play a protective role in both normal hamsters and those with cardiomyopathy.

PMID- 12193105
TI  - Stimulation of peroxisome-proliferator-activated receptor alpha (PPAR alpha)
      attenuates cardiac fibrosis and endothelin-1 production in pressure-overloaded
      rat hearts.
AB  - Endothelin-1 (ET-1) production is increased in hypertrophied hearts accompanied
      with fibrosis. ET-1 is a potent mitogen of fibroblasts and ET receptor
      antagonists are reported to inhibit the proliferation of fibroblasts and cardiac
      fibrosis. Peroxisome-proliferator-activated receptor alpha (PPAR alpha), one of
      the nuclear hormone receptors, suppresses activator protein-1 (AP-1), one of the
      nuclear transcription factors. Activation of PPAR alpha is reported to inhibit
      thrombin-induced ET-1 production by repressing the AP-1 signalling pathway in
      vascular endothelial cells. We investigated effects of the PPAR alpha activator
      fenofibrate (80 mg/kg per day, per os) on mRNA levels of ET-1, collagen type I
      and type III and histological features of myocardial fibrosis in hypertrophied
      rat hearts due to pressure-overload by abdominal aortic banding (AB). The
      treatment with fenofibrate or vehicle was started 7 days before the AB operation.
      Four days after the AB operation, fenofibrate treatment significantly reduced ET
      1 mRNA expression compared with vehicle treatment in AB rat hearts. Collagen type
      I and type III mRNA expression, and interstitial and perivascular fibrosis were
      attenuated in the fenofibrate-treated AB rat group. Since the ET-1 gene has AP-1
      response elements in the 5'-flanking region, it is suggested that myocardial
      fibrosis is effectively inhibited by fenofibrate through suppression of AP-1
      mediated ET-1 gene augmentation in the pressure-overloaded heart caused by aortic
      banding in rats.

PMID- 12193106
TI  - Effects of increased pulmonary flow on the expression of endothelial nitric oxide
      synthase and endothelin-1 in the rat.
AB  - The purpose of the study was to assess whether increased pulmonary flow and
      subsequent development of pulmonary vascular remodelling could alter the
      expression of endothelial nitric oxide synthase (eNOS) and endothelin-1 (ET-1) in
      the rat lung. Nine 42-day-old Wistar rats underwent abdominal aortocaval shunt to
      increase pulmonary blood flow for 12 weeks. The shunt resulted in significant
      medial hypertrophy of pulmonary artery without significant alterations in
      pulmonary or systemic blood pressure. Using competitive reverse transcription
      PCR, significant increases in the preproET-1 mRNA expression and eNOS mRNA
      expression in the lungs of rats with abdominal aortocaval shunt were detected.
      Increased eNOS protein in the lung of shunt rats was also found by Western blot
      analysis. However, the plasma ET-1 concentration in the pulmonary artery (sham:
      5+/-0.7 pg/ml; shunt: 6+/-0.8 pg/ml) or the lung ET-1 content (sham: 218+/-41
      ng/g protein; shunt: 224+/-40 ng/g protein) was unchanged. There was an elevated
      immunohistochemical expression of eNOS, but not ET-1, in the pulmonary vascular
      endothelium in rats with the shunt. These results suggest that eNOS and ET-1 may
      be involved in remodelling prior to the development of pulmonary hypertension.

PMID- 12193107
TI  - Interaction of endogenous endothelin-1 and inhaled nitric oxide in term and
      preterm infants.
AB  - The peptide endothelin-1 (ET-1) plays an unknown role in the pathogenesis and
      progression of two important neonatal pulmonary disorders, chronic lung disease
      (CLD) of prematurity and persistent pulmonary hypertension of the newborn (PPHN).
      Inhaled nitric oxide (INO) is a proven vasodilator therapy in PPHN and is an
      experimental therapy in CLD. We sought to determine the effects, if any, of the
      interaction of inhaled INO with ET-1 in these two separate disorders. Infants
      (n=21) with PPHN (mean gestation age, 39.4 weeks; mean birth weight, 3470 g) were
      treated with INO. All infants were <72 h of age at baseline. Plasma obtained at
      baseline and after 24 h of INO therapy was assessed for ET-1. The change in ET-1
      levels with INO was inversely correlated with change in arterial partial pressure
      of O(2) (r=-0.71, P=0.0003). A separate group of 33 patients with CLD (mean
      gestational age, 27 weeks; mean birth weight, 740 g; mean age, 19 days) had
      tracheal aspirate levels of ET-1 obtained before, during, and after 7 days'
      administration of INO. Values were normalized by soluble secretory component of
      IgA. Tracheal aspirate ET-1 levels were detectable before INO therapy. There was
      no significant change during or after treatment with INO. There was not a
      significant correlation between baseline fractional inspired O(2) and ET-1
      levels. There was a non-significant trend in the correlation between the change
      in ET-1 and the change in interleukin-8 levels in tracheal aspirate. This report
      confirms the presence of ET-1 in tracheal aspirate of premature infants who are
      developing CLD and reaffirms the presence of ET-1 in plasma of infants with PPHN.
      Short-term INO therapy was associated with a decrease in plasma ET-1 levels in
      PPHN, but did not affect tracheal aspirate ET-1 in CLD. Given the
      vasconstrictive, profibrotic, and proinflammatory properties of ET-1, specific ET
      1 receptor antagonists could be considered as candidates for trials as adjunct
      therapy in either or both of these disorders.

PMID- 12193108
TI  - Differential vasoactive response to endothelin receptor antagonists and
      prostacyclin in patients with severe pulmonary hypertension.
AB  - Pulmonary hypertension (PH) is a rare disease of the pulmonary vasculature with
      diverse pathogenetic mechanisms. Vasoactive substances such as endothelin A
      receptor (ET(A)) antagonists and prostanoids have been used to improve
      haemodynamics and clinical outcome. We compared the hemodynamic response to BQ
      123 (an ET(A) receptor antagonist) and prostacyclin or its analogue iloprost in
      ten patients (four men) with a mean age of 35.9+/-15.6 years. Seven patients had
      primary PH and three had PH owing to connective tissue disease. Patients
      underwent haemodynamic evaluation before and after administration of intra-atrial
      BQ-123 (200 mmol/min for 60 min), intravenous prostacyclin (3 ng x kg(-1) x min(
      1) for 4 h) or iloprost as an aerosol (100 microg over 24 h). Response to
      vasodilator administration was defined as >15% decrease in pulmonary vascular
      resistance index (PVRI). Of the ten patients, five showed a response to BQ-123
      and eight responded to prostanoids. Four patients were responders and one patient
      was a non-responder to both agents. PVRI decreased by 16.6+/-13.4% with BQ-123,
      and 24.4+/-15.7% with prostanoids (not statistically significant). The aetiology
      of PH did not affect the response to either drug. In conclusion, response to
      ET(A) antagonist or prostanoid administration can be achieved in a large group of
      patients with severe PH, however few patients respond identically to both agents.
      These findings are consistent with a multifactorial mechanism involved in this
      disease.

PMID- 12193109
TI  - Endothelin-1 acts as a survival factor in ovarian carcinoma cells.
AB  - The aim of this study was to evaluate the role of endothelin-1 (ET-1) in the
      sensitivity of ovarian carcinoma to paclitaxel, one of the most common drugs used
      for the management of this tumour histotype. ET-1 is a powerful mitogenic peptide
      produced by ovarian carcinomas and it acts as an autocrine growth factor,
      selectively through ET(A) receptor (ET(A)R), which is predominantly expressed in
      this tumour. OVCA 433 and HEY, two ovarian carcinoma cell lines, which produce
      elevated amounts of ET-1 and express abundantly high-affinity ET(A)Rs, were used.
      As demonstrated by sub-G(1) peak in DNA content histograms and terminal
      transferase deoxytidyl uridine end labelling assay, we found that paclitaxel
      induces cytotoxic effect through the activation of apoptosis in both cell lines.
      When the treatment with paclitaxel was performed in association with ET-1,
      paclitaxel-induced apoptosis was inhibited. In order to evaluate which ET-1
      receptor mediated the effect of ET-1 on protection from paclitaxel-induced
      apoptosis, we performed experiments using two selective antagonists for ET(A)R
      (BQ-123) and for ET(B)R (BQ-788). We showed that ET(A)R blockade inhibits the ET
      1-induced survival activity against paclitaxel-mediated apoptosis. However, no
      effect was observed on blocking ET(B)R with BQ-788. Our results establish a novel
      role for ET-1 in determining survival of ovarian carcinoma cells and suggest that
      pharmacological ET(A)R blockade using a specific ET(A)R antagonist may provide a
      novel approach to the treatment of ovarian carcinoma in combination therapy.

PMID- 12193110
TI  - Endothelin-1 promotes proteolytic activity of ovarian carcinoma.
AB  - Endothelin-1 (ET-1) is a potent mitogenic and angiogenic factor for ovarian
      carcinoma cell lines, which acts selectively through the ET(A) receptor (ET(A)R).
      A previous study demonstrated that ET-1 is present at high concentrations in
      ovarian cancer ascites, indicating a direct role in the progression and
      metastasis of ovarian carcinoma. In this study, we investigated whether ET-1
      could induce production and activation of tumour-associated proteinases in
      ovarian carcinoma cells. As demonstrated by ELISA, we found that the secretion of
      matrix metalloproteinase (MMP)-2 and MMP-9, urokinase-type plasminogen activator
      and plasminogen activator inhibitor type-1 and -2 was upregulated by ET-1 in a
      dose-dependent manner in the HEY cell line. In addition, the MMPs in ET-1-treated
      cells are consistently active, as shown by MMP gelatinase activity assay.
      Finally, we demonstrated that BQ-123, an antagonist of ET(A)R, inhibited the ET-1
      induced tumour protease secretion and activity, suggesting that ET-1/ET(A)R may
      play an important role in the progression and metastasis of ovarian carcinoma,
      activating multiple proteinase cascades.

PMID- 12193111
TI  - Endothelin receptor blockade inhibits the growth of human papillomavirus
      associated cervical carcinoma.
AB  - Human papillomaviruses (HPVs) are associated with cervical cancer and interact
      with growth factors that may enhance malignant transformation of cervical
      carcinoma cells. Endothelin-1 (ET-1) is released from HPV-transfected
      keratinocytes and induces increased growth response in these cell lines in
      comparison with normal cells. HPV-positive cancer cells secrete ET-1 and express
      mRNA for ET-1 and its receptors, whereas HPV-negative carcinoma cell lines
      express only the ET(B) receptor (ET(B)R) mRNA and do not secrete ET-1. In HPV
      positive cancer cells, ET(A)R mediates the ET-1-induced mitogenic effect and
      sustains the basal growth rate of unstimulated cervical tumour cells. Therefore,
      ET-1 may be involved in the neoplastic growth of HPV-associated cervical
      carcinoma, where the increased ET-1 autocrine loop can be targeted for antitumour
      therapy. In the present work, the action of specific antagonists of ET(A)R (BQ
      123 and ABT-627), was analysed in CaSki and C33A cells that are derived from
      human cervical carcinoma. CaSki cells are HPV-16-positive, produce ET-1 and
      possess ET(A)R and ET(B)R, whereas the C33A line is HPV-negative, does not
      secrete ET-1 and has no ET(A)R. In HPV-positive cancer cells ABT-627 strongly
      inhibited the proliferation induced by ET-1 and substantially reduced the basal
      growth rate of unstimulated cervical tumour cells, whereas the ET(B)R antagonist
      had no effect. These results demonstrate that ET-1 participates in the
      progression of neoplastic growth in HPV-associated carcinoma, in which ET(A)R
      expression is increased and could be targeted for antitumour therapy. In
      conclusion, an ET-1 autocrine loop is involved in tumour cell proliferation via
      ET(A)R, and ABT-627 is effective in controlling proliferation of cervical
      carcinoma cells.

PMID- 12193112
TI  - Differential expression of neutral endopeptidase-24.11 (neprilysin) and
      endothelin-converting enzyme in human prostate cancer cell lines.
AB  - Neutral endopeptidase-24.11 (neprilysin; NEP/CD10) is a cell surface
      metallopeptidase expressed by prostatic epithelial cells that degrades various
      bioactive peptides including endothelin. Endothelin-converting enzyme (ECE), the
      key enzyme of endothelin biosynthesis, catalyses the final processing step in the
      pathway. Neuropeptide substrates of NEP, including endothelin, have been
      implicated in the growth of androgen-independent prostate cancer. We have
      surveyed the expression of NEP and ECE in a range of prostate cancer cell lines.
      Western analysis reveals that ECE-1 is expressed abundantly in all the malignant
      cell lines tested, except for LNCaP. In contrast, LNCaP cells express high levels
      of NEP, while NEP was not detected in PC-3, DU145 and other metastatic cell lines
      that were tested. Of the normal immortalized prostate epithelial cell lines,
      PNT1a shows equivalent amounts of NEP and ECE. PNT2-C2 shows poor NEP expression
      but an abundance of ECE. P4E6, by comparison, has low levels of both ECE and NEP.
      These differences in expression may render these cell lines useful in
      experimental models for future study. Benign prostatic hyperplasia primary
      epithelial cells express much higher levels of NEP than malignant primary
      epithelial cells, but neither show ECE expression. On the other hand, surrounding
      stromal cell populations have detectable ECE levels. An absence of ECE in
      malignant and benign prostatic hyperplasia cells of primary epithelial origin
      suggests an important role for stromal interaction and paracrine production of
      ECE within the host. The upregulation of ECE expression in metastatic cells in
      culture may be indicative of its role in metastatic progression. A differential
      profile of ECE and NEP could contribute to an abundance of mitogenic peptides
      aiding the progression of androgen-independent prostate cancer.

PMID- 12193113
TI  - ABT-627, a potent endothelin receptor A antagonist, inhibits ovarian carcinoma
      growth in vitro.
AB  - Endothelin-1 (ET-1) is present at high concentrations in ovarian cancer ascites
      and is overexpressed in primary and metastatic ovarian carcinomas. In these
      tumours the presence of ET-1 is associated with enhanced neovascularization and
      with vascular endothelial growth factor (VEGF) expression. In these tumour cells,
      ET-1 acts as an autocrine growth factor selectively through the receptor ET(A),
      which is predominantly expressed in tumour cells. Furthermore, ET-1 produced by
      ovarian tumour cells stimulates VEGF production and VEGF-mediated angiogenic
      effects through ET(A) binding. These results demonstrate that activation of the
      ET(A) in ovarian carcinoma cells promotes cell proliferation, neovascularization
      and invasion, which are the principal hallmarks of malignant transformation. The
      present study was designed to investigate the effects of the ET(A)-selective
      antagonist ABT-627 on the ET-1-induced mitogenic effect in both primary cultures
      (PMOV1 and PMOV2) and cell lines (OVCA 433 and HEY) of ovarian carcinoma. All
      tumour cells express the components of the ET-1 system and secrete ET-1. ET(A)
      blockade by ABT-627 inhibits ET-1-induced mitogenic effects. The ET(B) antagonist
      BQ-788 is ineffective although all cell lines express both ET(A) and ET(B) mRNAs.
      In conclusion, our results demonstrate that ABT-627 is capable of inhibiting the
      proliferative activity of ET-1, suggesting that this potent ET(A) antagonist may
      provide a novel approach to the multidisciplinary treatment of ovarian carcinoma.

PMID- 12193114
TI  - Endothelins may modulate invasion and proliferation of Ewing's sarcoma and
      neuroblastoma.
AB  - Tumours of the Ewing's sarcoma (ES) family and neuroblastoma (NBL) were examined
      by reverse transcriptase-PCR for expression of mRNA for endothelin (ET) receptors
      ET-A and ET-B, and the ligands ET-1, ET-2 and ET-3. The effect of ET-1, ET-3, an
      ET-1-neutralizing antibody and ET-A receptor antagonist BQ-123 on cell
      proliferation was examined using an ELISA. Loss of ET-B receptor mRNA occurred in
      57% of ES and 42% of NBL tumours. This appeared to be associated with the
      presence of metastatic disease and disease progression. ET-A receptor mRNA was
      expressed in all ES and 85% of NBL tumours, and in all ES and NBL cell lines
      examined. All ET ligands were detected in NBL cell lines, but only ET-1 and ET-2
      were expressed in ES cell lines. Treatment of ES and NBL cells with ET-1
      increased proliferation, but ET-3 had no effect. Incubation of ES and NBL cells
      with an ET-1-neutralizing antibody or BQ-123 decreased proliferation. The ET-3
      ligand and ET-B receptor may be associated with migration and metastasis of ES
      and NBL, whereas ET-1 (acting through the ET-A receptor) may regulate their
      proliferation.

PMID- 12193115
TI  - Effects of periodontopathic bacteria on the expression of endothelin-1 in
      gingival epithelial cells in adult periodontitis.
AB  - Adult periodontitis, which is the major cause of adult tooth loss, is commonly
      characterized by chronic inflammatory disease caused by infection with
      periodontopathic bacteria such as Porphyromonas gingivalis. Our aims in the
      present study were to examine the expression of endothelin-1 (ET-1) in cultured
      HEp-2 epithelial cells after infection with P. gingivalis, and in gingival tissue
      from adult periodontitis patients. The cell lines were infected with the strains
      P. gingivalis 33277 and 381 for assessment of bacterial invasion using an
      antibiotic protection assay, and the expression of ET-1, inflammatory cytokines
      and cell adhesion molecules was examined by ELISA and reverse transcription-PCR.
      The expression of ET-1, as well as that of interleukin-1 beta, interleukin-8 and
      ICAM-1 (intercellular cell adhesion molecule 1), was induced significantly in a
      time-dependent manner, whereas the expression of MCP-1 (monocyte chemotactic
      protein-1), RANTES (regulated upon activation, normal T-cell expressed and
      secreted) and VCAM-1 (vascular cell adhesion molecule 1) was not. Furthermore, in
      gingival tissues from adult periodontitis patients, we also observed increased
      expression of ET-1 mRNA compared with tissue from normal healthy donors. These
      results suggest that infection by periodontopathic bacteria up-regulates the
      expression of ET-1, together with that of inflammatory cytokines and ICAM-1, in
      gingival epithelial cells, and that ET-1 expression may be closely involved in
      the regulation of cytokine responses and cell-cell adhesion in adult
      periodontitis lesions.

PMID- 12193116
TI  - Effects of endothelin receptor antagonists on endothelin-1 and inducible nitric
      oxide synthase genes in a rat endotoxic shock model.
AB  - Levels of the endothelium-derived vasoconstrictor endothelin (ET)-1 and the
      vasodilator nitric oxide (NO) are markedly increased in endotoxic shock, although
      the pathophysiological role of ET-1 and its relation to NO under septic
      conditions remains obscure. To delineate the roles of ET-1 and the ET receptors,
      and the NO/inducible NO synthase (iNOS) system in endotoxic shock, we examined
      the gene expression of ET-1, ET receptors A and B (ETA and ETB) and iNOS in the
      heart and the liver of a rat endotoxic shock model, and we studied the effects of
      ET receptor antagonists on haemodynamics, survival rate and expression of ET-1,
      ET receptors and iNOS. Administration of bacterial lipopolysaccharide (LPS) into
      rats caused a profound hypotension with resultant death. However, these effects
      were blocked by a non-selective ETA/ETB receptor antagonist (TAK044), but not by
      an ETA-selective antagonist (BQ123). Injection of LPS caused a marked elevation
      in the plasma levels of both ET-1 and NO, which were not affected by treatment
      with either ET receptor antagonist. Administration of LPS caused increases in
      levels of ET-1, ETB and iNOS mRNA in the heart and the liver, whereas ETA mRNA
      expression was markedly downregulated in these organs. These results suggest that
      ET receptor subtype genes are differentially regulated in major organs from
      endotoxic shock rats, and that non-selective ET receptor antagonists ameliorate
      endotoxin-induced hypotension and death irrespective of iNOS-derived NO.

PMID- 12193117
TI  - Haemodynamic and hormonal changes during haemorrhage in conscious dogs treated
      with an endothelin-A receptor antagonist.
AB  - This study compares the haemodynamic and hormonal responses during haemorrhage of
      conscious dogs pre-treated with an endothelin-A (ET-A) receptor inhibitor. The
      dogs were studied in two different randomized groups: the control group and a
      group that was given the ET-A receptor antagonist ABT-627 (as a bolus of 1 mg x
      kg of body weight(-1) followed by 0.01 mg x kg body weight(-1) x min(-1)
      intravenously). The time-course was the same for both groups: after a 1 h
      baseline period (pre-haemorrhage), blood (25 ml x kg of body weight(-1)) was
      withdrawn within 5 min. Haemodynamics were continuously recorded and hormone
      levels measured after 1 h (post-haemorrhage). Thereafter, the blood withdrawn was
      retransfused within 5 min and haemodynamics again observed for 1 h (post
      retransfusion). In ABT-627-treated dogs, the decrease in mean arterial pressure
      from 87+/-3 to 64+/-3 mmHg (P<0.05 versus pre-haemorrhage), and cardiac output
      from 2.1+/-0.1 to 1.3+/-0.1 l x min(-1) (P<0.05 versus pre-haemorrhage) and the
      increase in systemic vascular resistance from 3286+/-174 to 4211+/-230 dyn.s.cm(
      5) (P<0.05 versus pre-haemorrhage) during acute haemorrhage are comparable with
      controls. During haemorrhage in controls, vasopressin levels increased from 0+/-0
      to 13+/-2 pg x ml(-1) (P<0.05 versus pre-haemorrhage), angiotensin II levels
      increased from 9+/-1 to 28+/-9 pg x ml(-1) (P<0.05 versus pre-haemorrhage) and
      adrenaline levels increased from 134+/-22 to 426+/-74 pg x ml(-1) (P<0.05 versus
      pre-haemorrhage) whereas noradrenaline levels did not change (approx. 200 pg x
      ml(-1)). In ABT-627-treated dogs, vasopressin levels increased from 0.2+/-0.0 to
      22.2+/-6.1 pg x ml(-1) (P<0.05 versus pre-haemorrhage and P<0.05 versus control),
      angiotensin II levels increased from 8+/-1 to 37+/-8 pg x ml(-1) (P<0.05 versus
      pre-haemorrhage), noradrenaline levels increased from 147+/-16 to 405+/-116 pg x
      ml(-1) (P<0.05 versus pre-haemorrhage) and adrenaline levels did not change (200
      pg x ml(-1)) during haemorrhage. We conclude from our results that dogs receiving
      the selective ET-A inhibitor ABT-627 seem to show a different hormonal response
      after haemorrhage compared with controls, displaying considerably higher
      noradrenaline concentrations. Independent of ET-A receptor inhibition, cardiac
      output during haemorrhage was maintained within the control range. This may
      indicate that the organism is defending blood flow (cardiac output) over blood
      pressure during haemorrhage, and that this defence strategy is not compromised by
      ET-A receptor inhibition.

PMID- 12193118
TI  - Endothelin ET(B) receptor-mediated mechanisms involved in oleic acid-induced
      acute lung injury in mice.
AB  - The receptors underlying the endothelin-dependent component of lung plasma
      extravasation and leucocyte infiltration induced by oleic acid were assessed in
      mice. Oleic acid (1 mg.kg(-1) intravenously), but not endothelin-1 (up to 1
      nmol.kg(-1) intravenously), increased accumulation of Evans blue in the lungs
      (excluding the trachea and main bronchi) from 11.8+/-3.9 to 98.6+/-10.7 microg 1
      h after injection. Bosentan, the antagonist of endothelin receptors (ET(A) and
      ET(B)) or the selective ET(B) receptor antagonists Ro 46-8443 or A-192621
      (administered 1 h before oleic acid at doses of 30, 10 and 30 mg x kg(-1)
      respectively) reduced the effect of oleic acid by 71%, 58% and 79% respectively.
      However, the selective ET(A) receptor antagonist A-127722.5 (10 mg x kg(-1)) was
      inactive. Oleic acid (2 mg xkg(-1), intravenously) raised the number of total
      leucocytes, mononuclear cells and neutrophils in broncho-alveolar lavage fluid 4
      h after injection. Bosentan and Ro 46-8443 (at doses of 30 and 10 mg x kg(-1)
      respectively) inhibited the neutrophil infiltration induced by oleic acid by
      approx. 80%. None of the antagonists modified control (basal) pulmonary
      microvascular permeability or total and differential cell counts. Thus,
      endogenous endothelins, acting via ET(B) receptor-dependent mechanisms, play a
      major role in oleic acid-induced lung injury in the mouse by promoting
      infiltration of circulating neutrophils and enhancement of pulmonary
      microvascular plasma extravasation. These findings suggest that either ET(B) or
      mixed ET(A)/ET(B) receptor antagonists might be beneficial in the treatment of
      the adult respiratory distress syndrome.

PMID- 12193119
TI  - Impact of parainfluenza-3 virus infection on endothelin receptor density and
      function in guinea pig airways.
AB  - We examined the impact of parainfluenza-3 (P-3) respiratory tract viral infection
      on the density and function of endothelin (ET) receptor subtypes (ET(A) and
      ET(B)) in guinea pig tracheal smooth muscle. Total specific binding of [(125)I]ET
      1 and the relative proportions of ET(A) and ET(B) binding sites for this ligand
      were assessed at day 0 (control) and at 2, 4, 8 and 16 days post-inoculation. At
      day 0, the proportions of ET(A) and ET(B) binding sites were 30% and 70%
      respectively. Total specific binding was significantly reduced at day 4 post
      inoculation (32% reduction, n=8-12, P<0.05) and was largely due to a
      corresponding fall in ET(B) receptor density at this time point (38% reduction,
      n=8-12, P<0.05). The density of ET(A) receptors also fell significantly at day 8
      post-inoculation (33% reduction, n=6-12, P<0.05). By day 16 post-inoculation, the
      densities of ET(A) and ET(B) receptors had recovered to control values. The ratio
      of ET(A):ET(B) receptor subtypes did not alter with P-3 infection. While P-3
      infection reduced the density of tracheal smooth muscle ET(A) and ET(B)
      receptors, the contractile sensitivity and maximum response to carbachol and ET-1
      was not altered in tissue from day 4 post-inoculation compared with the control.
      There seems to be a significant functional reserve for both receptor subtypes in
      this species that buffers the impact of P-3 infection on airway smooth muscle
      responsiveness to ET-1.

PMID- 12193120
TI  - Enhanced ET(A) receptor-mediated contractile function is associated with reduced
      ET(A) receptor density in sheep bronchial explants maintained in culture.
AB  - We are interested in developing an airway explant culture system using sheep
      bronchi in which to establish respiratory viral infection and from which tissue
      can be used for functional, biochemical and immunohistochemical studies involving
      the endothelins (ETs). Freshly harvested sheep bronchial airway smooth muscle
      contains a homogeneous population of the ET(A) receptor. However, the potency of
      ET-1 and maximum contractile response of sheep bronchial explants to ET-1
      increased with time in culture, despite these parameters remaining constant for
      carbachol in explants maintained for up to 48 h. The possibility that this was
      caused by changes in ET receptor density was assessed using light microscopic
      quantitative autoradiography. In view of the increased responsiveness to ET-1 in
      cultured explants, it was surprising to demonstrate a significant decrease in
      total ET receptor (59+/-6% compared with the initial value, n=4-5; P<0.01) and
      ET(A) receptor (51+/-2% compared with the initial value, n=4-5, P<0.01) density
      in sheep bronchial explants after 48 h. No ET(B) receptors were detected. Thus,
      the culture of sheep bronchial explants was associated with an increase in ET(A)
      receptor-mediated contractile function that was accompanied by a decrease in
      ET(A) receptor density. In addition, the structural integrity of the ciliated
      epithelium was preserved using this culture protocol, a feature that is critical
      to successful respiratory viral infection. The significant changes in ET receptor
      density and function in these bronchial explants must be carefully considered
      when assessing any effects of respiratory viral infection in this model.

PMID- 12193121
TI  - Role of endothelin-converting enzyme, chymase and neutral endopeptidase in the
      processing of big ET-1, ET-1(1-21) and ET-1(1-31) in the trachea of allergic
      mice.
AB  - The present study examined the roles of endothelin-converting enzyme (ECE),
      neutral endopeptidase (NEP) and mast cell chymase as processors of the endothelin
      (ET) analogues ET-1(1-21), ET-1(1-31) and big ET-1 in the trachea of allergic
      mice. Male CBA/CaH mice were sensitized with ovalbumin (10 microg) delivered
      intraperitoneal on days 1 and 14, and exposed to aerosolized ovalbumin on days
      14, 25, 26 and 27 (OVA mice). Mice were killed and the trachea excised for
      histological analysis and contraction studies on day 28. Tracheae from OVA mice
      had 40% more mast cells than vehicle-sensitized mice (sham mice). Ovalbumin (10
      microg/ml) induced transient contractions (15+/-3% of the C(max)) in tracheae
      from OVA mice. The ECE inhibitor CGS35066 (10 microM) inhibited contractions
      induced by big ET-1 (4.8-fold rightward shift of dose-response curve; P<0.05),
      but not those induced by either ET-1(1-21) or ET-1(1-31). The chymase inhibitors
      chymostatin (10 microM) and Bowman-Birk inhibitor (10 microM) had no effect on
      contractions induced by any of the ET analogues used. The NEP inhibitor CGS24592
      (10 microM) inhibited contractions induced by ET-1(1-31) (6.2-fold rightward
      shift; P<0.05) but not ET-1(1-21) or big ET-1. These data suggest that big ET-1
      is processed predominantly by a CGS35066-sensitive ECE within allergic airways
      rather than by mast cell-derived proteases such as chymase. If endogenous ET-1(1
      31) is formed within allergic airways, it is likely to undergo further conversion
      by NEP to more active products.

PMID- 12193122
TI  - Elevated systemic levels of endothelin-1 and blood pressure correlate with
      blunted constrictor responses and downregulation of endothelin(A), but not
      endothelin(B), receptors in an animal model of hypertension.
AB  - Hypertension is a major risk factor in the development of cardiovascular disease.
      Adenovirus gene transfer of endothelin-1 (Ad.CMV.ET-1) in rats produced
      significant (5-fold) increases in plasma ET-1 and systemic blood pressure (46%) 4
      days after viral administration, compared with beta-galactosidase (Ad.CMV.beta
      gal) injected as control. The density (B(max)) of the ET receptor ET(A) measured
      in aortas was reduced significantly by more than 50% to 17+/-2 fmol.mg(-1) of
      protein for the Ad.CMV.ET-1 group compared with 39+/-6 fmol x mg(-1) of protein
      for the control. There was no change in the density of the smaller population of
      the ET(B) sub-type. In agreement, the ratio of ET(A) mRNA to cyclophilin mRNA (a
      housekeeping gene) measured by Northern analysis was reduced in Ad.CMV.ET-1 rats
      compared with controls. The ratio of mRNA encoding the ET(B) sub-type did not
      change. ET-1 vasoconstriction was significantly reduced (P<0.05) in aortas from
      Ad.CMV.ET-1-treated rats [pD(2)=8.67+/-0.14 (where pD(2) is -log(10)EC(50));
      n=11] versus the control (pD(2)=9.11+/-0.06; n=14) but there was no significant
      difference in the potency of two other vasoconstrictors tested (noradrenaline and
      Arg-vasopressin), indicating this was a specific effect on ET receptors. There
      was no change in the affinity of ET-1 binding to either receptor sub-type in the
      experimental group compared with the control, demonstrating that the attenuation
      in the constrictor response is the result of the reduced density of receptors
      rather than a change in affinity. The results show that ET(A) (but not ET(B))
      receptors are modulated in this experimental model of hypertension and provide
      further evidence for selective blockade of the ET(A) receptor as a therapeutic
      strategy.

PMID- 12193123
TI  - Effects of benazepril, an angiotensin-converting enzyme inhibitor, combined with
      CGS 35066, a selective endothelin-converting enzyme inhibitor, on arterial blood
      pressure in normotensive and spontaneously hypertensive rats.
AB  - Continuous intra-arterial administration of a selective endothelin-converting
      enzyme (ECE) inhibitor CGS 35066 at a dose of 30 mg/kg decreased the mean
      arterial blood pressure (MABP) in conscious unrestrained normotensive rats and
      spontaneously hypertensive rats (SHRs). At that dose, the magnitude of the
      antihypertensive effects was greater in SHRs than in normotensive rats.
      Additional administration of an angiotensin-converting enzyme (ACE) inhibitor
      benazapril (lotensin) further reduced MABP in normotensive rats and completely
      blocked hypertension in SHRs. However, when the selective ECE inhibitor was
      subsequently removed, blood pressure was less inhibited in normotenive rats
      whereas it remained strongly inhibited in SHRs by the ACE inhibitor alone. These
      results imply that simultaneous treatment with benazepril and CGS 35066 gave
      additive antihypertensive effects in normotensive rats but not in SHRs, when both
      compounds were administered at a dose of 30 mg/kg. Our results suggest that: (i)
      the endothelin (ET) system together with the renin-angiotensin system contribute
      to the maintenance of blood pressure in normal healthy rats; (ii) while an ECE
      inhibitor acts as an antihypertensive agent on its own, the sole efficacy of ACE
      inhibitor at that dose is sufficient to block MABP without the participation of
      the ET system in SHR.

PMID- 12193124
TI  - Effects of a selective ET(A)-receptor antagonist, atrasentan (ABT-627), in murine
      models of allergic asthma: demonstration of mouse strain specificity.
AB  - Asthma is a chronic respiratory disease that is characterized by airway
      inflammation, bronchoconstriction and the influx of pro-inflammatory cells,
      mostly eosinophils in the lung tissue and bronchoalveolar space. Amongst the many
      physiopathological roles attributed to endothelins (ETs), one is to modulate
      pulmonary functions. It is established that Balb/c mice develop allergen-induced
      Th(2)-cytokine gene expression, airway inflammation and hyper-responsiveness
      whereas C57Bl/6 mice are much less reactive. In the present study, we
      investigated the roles of ETs in these two murine models of allergic asthma (AA).
      Mice were sensitized and challenged with either saline (S) and/or ovalbumin (O)
      over 6 weeks (groups S/S and O/O) and treated chronically with ABT-627 or its
      vehicle. Twenty-four hours after the last sensitization, challenged mice
      developed a marked airway inflammatory response characterized by the accumulation
      of total inflammatory cells (a 21-fold increase) in the bronchoalveolar space,
      similar in both mouse strains. The increase in eosinophils was marked in both
      groups, representing 98% of total cell count in O/O versus <1% in S/S.
      Macrophages were also increased 3-fold in both strains. ABT-627 did reduce the
      accumulation of macrophages in both stains (36 to 53%) whereas it blocked by 76%
      the influx of eosinophils in Balb/c but not in C57Bl/6 mice. These results show
      that ET(A)-receptor antagonism is more effective against O/O-induced AA in Balb/c
      mice, even though both strains were associated with the same increase in key pro
      inflammatory cells in the bronchoalveolar space. It is unclear whether this is
      due to a lack or a disproportionate expression of ET(A) receptors in these two
      murine strains, or in post-receptor transduction modulation, or different
      regulation of ET receptors in various pulmonary cells, after sensitization and
      challenge.

PMID- 12193126
TI  - Coronary effects of endothelin-1 during acute hypertension in anaesthetized
      goats.
AB  - The coronary effects of endothelin-1 (ET-1) during acute hypertension were
      examined in anesthetized goats, where the left circumflex coronary artery flow
      was electromagnetically measured and hypertension was induced by constriction of
      the thoracic aorta. In six non-treated goats, aortic constriction increased
      arterial pressure (mean arterial pressure=128+/-5 mmHg) and coronary flow (by
      34%) without changing coronary vascular conductance. In this case, ET-1 (0.01-0.3
      nmol) when injected intracoronarily, decreased coronary vascular conductance,
      which was similar in hypertension and in normotension. In eight N(G)-nitro-L
      arginine methyl ester-treated goats, aortic constriction increased arterial
      pressure (mean arterial pressure=131+/-5 mmHg) and coronary flow (by 26%) and
      decreased coronary vascular conductance (by 17%). In this case, ET-1 (0.01-0.3
      nmol) also decreased coronary vascular conductance, which was similar in N(G)
      nitro-L-arginine methyl ester-treated hypertension that observed in normotension.
      Therefore, acute hypertension attenuates the coronary vasoconstriction caused by
      ET-1, and this attenuation might be related to mechanisms other than changes in
      NO release.

PMID- 12193125
TI  - Effects of a selective endothelin A receptor antagonist, ABT-627, in healthy
      normotensive anaesthetized rats developing acute pulmonary air embolism.
AB  - Acute pulmonary air embolism (APAE) injures the vascular endothelium in the lung
      and results in pulmonary hypertension (PH). Endothelins (ETs), a family of potent
      vasoactive peptides, are known to be associated with PH of various aetiologies.
      We evaluated the effects of ABT-627, a selective ET(A) receptor (ET(A)-R)
      antagonist in a rat model of APAE over 3 h. APAE rats developed a higher right
      ventricular systolic pressure (RVSP), lower mean arterial blood pressure (MABP),
      and had lower PaO(2). At 3 h, arterial plasma levels of ET-1 were increased. ABT
      627-treated controls showed no effects. However, ABT-627 significantly lowered
      RVSP during APAE, abolished the short recovery phase (within 10-25 min) of MABP
      without affecting the subsequent lowering of MABP, and improved oxygen saturation
      in APAE rats. These results show that ET(A)-R subtype is involved in the
      pathogenesis of APAE since a blockade of this receptor subtype attenuated the
      cardiopulmonary deterioration and improved blood gas exchanges in rats with this
      disease.

PMID- 12193127
TI  - Role of endothelin receptors in the hypertensive state of kinin B(2) knockout
      mice subjected to a high-salt diet.
AB  - Mice with disruption of the kinin B(2) receptor (B(2)KO mice) are sensitive to
      salt-rich diets, which causes hypertension. The aim of the study was to assess
      the role of endothelin-1 (ET-1) and angiotensin-II in hypertensive B(2)KO mice on
      a salt-rich diet. We also wanted to verify if there is an upregulation of the
      mRNA expression of the precursors or receptors for these hormones. Two groups of
      B(2)KO mice (20-25 g) were investigated. The first group received an 8% NaCl diet
      with 1% NaCl in drinking water (HS) and the second was fed with normal food with
      tap water (NS). The antagonists tested were the ET(A) receptor antagonist BQ-123
      (1 and 5 mg/kg), the ET(B) receptor antagonist BQ-788 (0.25 and 1 mg/kg), the
      angiotensin receptor type 1 antagonist losartan (10 mg/kg) and the angiotensin
      converting enzyme inhibitor captopril (3 mg/kg). These were injected
      intraperitoneally 30 min prior to blood pressure measurement by the tail-cuff
      method. We also studied the level of expression of preproET-1, ET-1 receptors,
      angiotensinogen and angiotensin receptors by RNA extraction from the heart and
      kidneys of these mice followed by reverse transcriptase (RT)-PCR. B(2)KO mice
      (HS) were hypertensive after 8 weeks compared with B(2)KO mice on normal diet
      (HS, 93.4+/-1.5 mmHg, n=7; NS, 61.4+/-2.7 mmHg, n=7). In the HS group, the mean
      arterial blood pressure was significantly reduced by BQ-123 (5 mg/kg) to 61.9+/
      1.8 mmHg (n=7), by BQ-788 (1 mg/kg) to 58.8+/-2.6 mmHg (n=6), by losartan (10
      mg/kg) to 73.2+/-1.7 mmHg (n=8) and by captopril (3 mg/kg) to 86.0+/-2.3 mmHg
      (n=8). The expression studied by RT-PCR did not show any difference (either in
      precursors or receptors expression) between hypertensive and normal mice. The
      four antagonists used seemed to reverse the hypertension. These results suggest
      that ET-1 and angiotensin-II are probably involved in the mechanism that leads to
      hypertension since the effect of these hormones is probably not compensated by
      kinins in B(2)KO mice. Further studies are necessary to understand the
      implication of the cross-talk between these hormones in the hypertensive state.

PMID- 12193129
TI  - Pathophysiological roles of Ca(2+) overload via the Na(+)/Ca(2+) exchanger and
      endothelin-1 overproduction in ischaemia/reperfusion-induced acute renal failure.
AB  - Using Na(+)/Ca(2+) exchanger (NCX1)-deficient mice, the pathophysiological role
      of Ca(2+) overload via the reverse mode of the Na(+)/Ca(2+) exchanger in
      ischaemia/reperfusion-induced renal injury was investigated. Since NCX1(-/-)
      homozygous mice die of heart failure before birth, we utilized NCX1(+/-)
      heterozygous mice. The ischaemia/reperfusion-induced renal dysfunction in
      heterozygous mice were significantly attenuated compared with cases in wild-type
      mice. Also, histological renal damage such as tubular necrosis and proteinaceous
      casts in tubuli in heterozygous mice were much less than that in wild-type mice.
      Ca(2+) deposition in necrotic tubular epithelium was observed more markedly in
      wild-type than in heterozygous mice. The increase in renal endothelin-1 (ET-1)
      content was significantly greater in wild-type than in heterozygous mice, and
      this reflected the difference in immunohistochemical ET-1 localization in
      necrotic tubular epithelium. We conclude that Ca(2+) overload via the reverse
      mode of Na(+)/Ca(2+) exchange, followed by renal ET-1 overproduction, plays an
      important role in the pathogenesis of ischaemia/reperfusion-induced acute renal
      failure.

PMID- 12193128
TI  - Endothelin receptor A blockade reduces proteinuria and vascular hypertrophy in
      spontaneously hypertensive rats on high-salt diet in a blood-pressure-independent
      manner.
AB  - The renal endothelin (ET) system is involved in the pathogenesis of kidney
      fibrosis as well as blood pressure control by regulating tubular sodium
      excretion. Long-term effects of ETA receptor blockade on blood pressure and
      kidney function in spontaneously hypertensive rats (SHRs) on a high-salt diet are
      unknown. We treated SHRs on a 6% (w/v) NaCl sodium diet (SHR-S) for 48 weeks with
      the ETA antagonist LU 135252 (whose selectivity for ETA is 150 times greater than
      for ETB) with 10, 30 and 100 mg x kg(-1) x day(-1) or placebo. The ETA antagonist
      had at no time-point any effect on blood pressure. Glomerular filtration rate was
      normal in SHR-S and not altered by LU 135252. However, urinary albumin excretion
      was markedly reduced by the ETA antagonist (SHR-S, 145+/-50 mg/day; SHR-S+10 mg x
      kg(-1) x day(-1) LU 135252, 33+/-11 mg/day, P<0.05 versus SHR-S; SHR-S+30 mg x
      kg(-1) x day(-1) LU 135252, 55+/-16 mg/day and SHR-S+100 mg x kg(-1) x day(-1) LU
      135252, 32+/-11 mg/day, P<0.05 versus SHR-S at both concentrations). Total
      urinary protein excretion was likewise significantly reduced by treatment with 10
      mg.kg(-1).day(-1) LU 135252 (SHR-S, 0.25+/-0.06 g/day; SHR-S+10 mg x kg(-1) x
      day(-1) LU 135252, 0.089+/-0.01 g/day, P<0.05 versus SHR-S). The higher dosages
      of LU 135252 showed only a trend towards reduction of total urinary protein
      excretion. Computer-aided image analysis after haematoxylin/eosin and periodic
      acid-Schiff staining revealed that treatment with 10 mg x kg(-1) x day(-1) LU
      135252 significantly reduces the media/lumen ratio of intrarenal arteries. Higher
      dosages of LU 135252 were less effective. Renal matrix protein synthesis in SHR-S
      was not altered by LU 135252. In conclusion, the renal ET system contributes in a
      blood-pressure-independent manner to the regulation of urinary protein excretion
      and renal vascular hypertrophy in SHR-S. Lower doses of the ETA antagonist were
      more effective, indicating that a potential additional blockade of the ETB
      receptor using higher doses of LU 135252 seems to oppose the beneficial effects
      of a sole ETA blockade. Urinary protein excretion is an independent risk factor
      of chronic renal failure, thus ETA antagonists might be a therapeutic tool to
      prevent proteinuria-induced chronic renal failure.

PMID- 12193130
TI  - Activity of the endothelin system in kidney allograft recipients is not
      associated with progression of chronic graft dysfunction.
AB  - Endothelin (ET) A receptor antagonists have been shown to be beneficial in rat
      models of chronic kidney allograft dysfunction. We investigated urinary and
      plasma ET-1 (uET-1, pET-1) and BigET-1 (uBigET-1, pBigET-1) concentrations, and
      plasma soluble ET-converting enzyme (ECE) concentration in 310 adult Caucasian
      kidney allograft recipients with graft survival of more than 2 years from the
      outpatients department of our clinic. All patients were on cyclosporine A- or
      FK506-based immunosuppression protocols. From all available measurements since
      transplantation, we calculated the slope of serum creatinine(-1)/year (slopeCrea)
      as a parameter for progression of chronic graft dysfunction, as well as the mean
      of serum creatinine (meanCrea) from most recent year before measurements as a
      parameter for actual graft function. The slope of urinary protein excretion/year
      (slopeProt) and mean of urinary protein concentration (meanProt) from most recent
      year was calculated analogue. uET-1 and uBigET-1 were adjusted for protein
      excretion by calculating uET-1/meanProt and uBigET-1/meanProt. Blood and urine
      probes for measurements were always drawn immediately before morning dosage of
      immunosuppressants. There was no significant correlation of any measured
      component of the ET system with slopeCrea or slopeProt. MeanCrea (mg/dl) was
      significantly correlated with pBigET-1 (fmol/ml) and pET-1 (fmol/ml) (pBigET-1:
      r=0.179, P=0.001; pET-1: r=0.161, P=0.009). The other measured components of the
      ET systems were not significant correlated with meanCrea. In conclusion, the
      actual graft function is associated with elevated pET-1 and BigET-1
      concentrations as it is well known from other forms of impaired kidney function.
      However, the actual concentration of ET-1, soluble ECE, and BigET-1 in urine and
      plasma in our study is not associated with parameters for progression of chronic
      graft dysfunction.

PMID- 12193131
TI  - Interaction of the endothelin system and calcineurin inhibitors after kidney
      transplantation.
AB  - Plasma endothelin (ET)-1 concentrations have been shown to be elevated in
      patients receiving calcineurin-inhibitors (CI). We investigated urinary and
      plasma ET-1 (uET-1, pET-1), BigET-1 (uBigET-1, pBigET-1) concentrations, and
      plasma soluble endothelin-converting enzyme (ECE) concentrations in 381 adult
      caucasian kidney allograft recipients with graft survival of more than 2 years
      from the outpatients department of our clinic. Blood and urine probes were always
      drawn immediately before morning dosage of immunosuppressants. Mean of urinary
      protein excretion (meanProt) and mean of serum creatinine (meanCrea) were
      calculated from all available measurements in the most recent year. uET-1 and
      uBigET-1 were adjusted for urinary protein excretion by calculating uET
      1/meanProt and uBigET-1/meanProt. Patients (n=310) were on a cyclosporine A or
      FK506 (CI-group) based immunosuppression protocol, and 71 patients were
      immunosuppressed without use of CI (nonCI group). Time since transplantation was
      similar in both groups (mean+/-S.D.; CI-group: 7.55+/-2.50; nonCI-group: 7.74+/
      3.06 years, P=0.240) as well as meanCrea (mean+/-S.D.; CI-group: 1.97+/-1.34;
      nonCI-group: 1.77+/-1.29 mg/dl, P=0.326). pET-1 was significantly higher in the
      CI-group, compared with nonCI (mean+/-S.D.; 0.87+/-1.4 versus 0.56+/-0.76
      fmol/ml, P=0.011). pBigET-1 was similar (mean+/-S.D.; 0.85+/-1.41 versus 0.70+/
      1.21 fmol/ml, P=0.33). ECE concentrations were higher in the CI group (mean+/
      S.D.; 14.30+/-18.02 versus 9.23+/-7.42 ng/ml, P=0.001). uET-1/meanProt and uBigET
      1/meanProt concentration were similar in the CI-group compared with the nonCI
      group (mean+/-S.D.; uET-1/meanProt: 15+/-24 versus 21+/-40 pmol/g, P=0.139;
      uBigET-1/meanProt: 34+/-55 versus 19+/-23pmol/g, P=0.248). pET-1 elevation in
      patients receiving CI might be more likely to be due to elevated conversion of
      pBig-ET-1 by more ECE, and not to higher concentrations of pBigET-1.

PMID- 12193132
TI  - Arteriojugular endothelin-1 gradients in aneurysmal subarachnoid haemorrhage.
AB  - Plasma endothelin (ET) is elevated in patients with vasospasm following
      subarachnoid haemorrhage (SAH). However, systemic levels provide no indication
      regarding local production in the brain, and late elevation may be a consequence
      rather than a cause of vasospasm. We measured arteriojugular (AJ) gradients of ET
      1 in 17 patients over the first week after SAH, and related these to the
      subsequent development of vasospasm. Daily, paired arterial and jugular bulb
      blood samples were obtained up to seven days post SAH, and assayed for ET-1 using
      radioimmunoassay. Systemic levels and AJ gradients were compared in patients with
      and without vasospasm. Significant AJ gradients were observed for ET-1 (P<0.01).
      These differences remained significant in the subgroup of patients who developed
      vasospasm (0.12+/-0.05 pmol/l; P<0.05), in whom AJ gradients represented 25+/-7%
      of systemic levels (0.84+/-0.05 pmol/l). AJ gradients did not reach significance
      in patients who did not develop vasospasm (0.09+/-0.07 pmol/l; P=0.2). Systemic
      ET-1 levels and AJ gradients were unrelated to SAH grade, surgical or
      endovascular interventions, or extracranial complications. AJ gradients in the
      first week following SAH suggest early production of ET-1 in the cerebrovascular
      bed. However, early systemic ET-1 levels did not discriminate between patients
      with and without vasospasm. Larger AJ differences may predict vasospasm, but
      further work is needed to confirm this observation. AJ gradient measurement may
      provide a useful technique for investigating the role of other peptides in acute
      brain injury.

PMID- 12193133
TI  - Endothelin in human cerebrovascular nerves.
AB  - Novel data is presented from this electron-immunocytochemical study that
      demonstrates endothelin-containing cerebrovascular nerves in the human middle
      cerebral artery.

PMID- 12193134
TI  - Effect of the novel endothelin(A) receptor antagonist LU 208075 on contraction
      and relaxation of isolated rat basilar artery.
AB  - Increased levels of endothelin (ET)-1 and bigET-1 may be responsible for enhanced
      cerebroarterial resistance under pathologic conditions. Therefore, the effect of
      LU 208075, a novel ET(A)-selective receptor antagonist was determined. The aim of
      the study was to investigate in vitro the inhibitory effect of LU 208075 on ET-1
      and bigET-1 induced contraction and relaxation in rat basilar artery segments.
      Segments with (E+) and without (E-) endothelium were prepared for the measurement
      of isometric force. Concentration-effect curves (CECs) were constructed by
      cumulative application of ET-1 or bigET-1. The shift of the CECs in the presence
      of LU 208075 against the control curve was determined. Relaxation was
      investigated on precontracted segments, calculated in percentage decrease of
      precontraction and compared by the pD(2) and E(max). ET-1 and bigET-1 induced
      contraction was dose dependently inhibited by LU 208075. Shifts of the CECs in
      the presence of LU 208075 (10(-6) M and 10(-5) M) were for ET-1 (1) in E+: 4.4
      and 19.7; (2) in E-: 8.1 and 60.4 and for bigET-1 (3) in E+: 10.8 and (4) in E-:
      26.0 respectively. LU 208075 (10(-5) M) completely inhibited bigET-1-induced
      contraction. Relaxation by ET-1 or bigE-1 was only observed in the presence of LU
      208075. CECs were shifted to the right by LU 208075 (10(-5) M) by a factor of 24
      (ET-1) and 4.5 (bigET-1). E(max) values were 45+/-18% and 51+/-15% (ET-1; in the
      presence of 10(-5) and 10(-6) M LU 208075 respectively), and 56+/-20% and 49+/
      17% (bigET-1; in the presence of 10(-5) and 10(-6) M LU 208075 respectively). The
      data suggests a competitive ET(A)-receptor inhibition by LU 208075. The enhanced
      inhibitory effect on bigET-1-induced contraction could indicate an additional
      inhibitory effect on endothelin-converting enzyme activity. The pronounced effect
      on E-vessels and the inhibition of relaxation may suggest an ET(B) receptor
      affinity.

PMID- 12193135
TI  - Oral administration of an inhibitor of endothelin-converting enzyme attenuates
      cerebral vasospasm following experimental subarachnoid haemorrhage in rabbits.
AB  - Increasing evidence has implicated endothelin-1 (ET-1), a potent vasoconstrictive
      peptide, in the pathophysiology of cerebral vasospasm after subarachnoid
      haemorrhage (SAH). Endothelin-converting enzyme-1 (ECE-1), the protease involved
      in the final step of post-translational processing of ET-1, cleaves the inactive
      precursor big ET-1 at the Trp(21)-Val (22) peptide bond. In our previous study,
      we found that an inhibitor of ECE-1, CGS 26303, could prevent and reverse the
      arterial narrowing after SAH in rabbits. CGS 26393, a prodrug of CGS 26303, is an
      orally active, long-acting inhibitor of ECE-1. The present study examined the
      effects of CGS 26393 on the prevention and reversal of cerebral vasospasm after
      SAH. New Zealand white rabbits were subjected to experimental SAH by injecting
      autologous blood into the cisterna magna. In the prevention study, the drug was
      given orally 1 h before the induction of SAH. All drug treatments in the reversal
      study were initiated at 23 h after induction of SAH. One of three dosages (3, 10
      or 30 mg/kg) of CGS 26393 or vehicle was administrated orally twice daily, and
      all animals were sacrificed by perfusion and fixation 48 h after SAH. Basilar
      arteries were removed and sectioned, and cross-sectional areas were measured.
      Cerebrospinal fluid (CSF) was collected prior to perfusion. Oral administration
      of CGS 26393 attenuated SAH-induced cerebral vasospasm in a dose-dependent manner
      in both the prevention and reversal groups. These effects achieved statistical
      significance at all dosages when compared with the SAH-only or SAH plus vehicle
      groups. Moreover, the attenuation of vasospasm following oral administration of
      CGS 26393 was more efficacious than that obtained with bolus injections of CGS
      26303. The levels of free CGS 26303 in the CSF were increased in a dose-dependent
      manner in all three CGS 26393-treated groups. This study provides the first
      evidence that oral administration of an inhibitor of ECE-1, CGS 26393, is capable
      of preventing and reversing cerebral vasospasm following SAH. These findings also
      reinforce evidence demonstrating that treatment with an ECE-1 inhibitor is a
      potentially viable therapeutic approach for reducing cerebral vasospasm after
      SAH.

PMID- 12193137
TI  - The effect of diabetes on endothelin, interleukin-8 and vascular endothelial
      growth factor-mediated angiogenesis in rats.
AB  - In diabetes mellitus, there is a problem of both premature atherosclerosis as
      well as impaired collateralization. Studies were performed using the rat corneal
      angiogenesis model as a surrogate for collateralization to determine the effect
      of diabetes mellitus on endothelin (ET)-1, ET-3, vascular endothelial growth
      factor (VEGF) and interleukin-8 (IL-8)-mediated angiogenesis. In an initial group
      of experiments, streptozotocin-induced diabetes resulted in impairment of ET-1
      mediated angiogenesis from 69% to 32%, but was only impaired from 74% to 59% for
      ET-3. When rats were fluid-resuscitated, mortality fell, and the incidence of
      inhibition of angiogenesis decreased for ET-1, but was still at 47%. Inhibition
      of ET-3-mediated angiogenesis in fluid-resuscitated rats was essentially
      unaffected from 74% to 75%. Studies of VEGF and IL-8 in fluid-resuscitated rats
      demonstrated that VEGF-mediated angiogenesis was only inhibited from 49% to 45%,
      but there was inhibition of IL-8-mediated angiogenesis from 62% to 31%. We
      concluded that there may be two mechanisms by which ET-1-mediated corneal
      angiogenesis is inhibited: a decrease in intravascular volume and dynamic forces
      affecting angiogenesis, and a direct effect of diabetes on some aspect of cell
      growth or angiogenic process. Diabetes also appeared to inhibit IL-8-mediated
      angiogenesis, but had very little or no effect on ET-3- or VEGF-mediated
      angiogenesis.

PMID- 12193136
TI  - Endothelin-stimulated glucose uptake: effects of intracellular Ca(2+), cAMP and
      glucosamine.
AB  - Endothelin-1 (ET-1) is a 21-amino-acid peptide that binds to G-protein-coupled
      receptors to evoke biological responses. Previously we have shown that ET-1
      stimulates glucose uptake in 3T3-L1 adipocytes and neonatal rat cardiomyocytes,
      but the mechanism is not completely understood. ET-1 is known to modulate
      intracellular Ca(2+) and cAMP levels. Depletion of intracellular Ca(2+) by
      treating 3T3-L1 adipocytes with EDTA and 1,2-bis(2-amino-5-methylphenoxy)ethane
      N,N,N',N'-tetra-acetic acid tetra-acetoxymethyl ester (MAPTAM) did not have a
      significant effect on ET-1-induced glucose uptake. Forskolin, a potent stimulator
      which stimulates adenylate cyclase and increases the intracellular cAMP level,
      partially inhibited insulin-stimulated glucose uptake in 3T3-L1 cells, but had no
      significant impact on the effect of ET-1. Forskolin also did not show an effect
      on the tyrosine phosphorylation of a 75 kDa protein induced by ET-1. Glucosamine
      treatment causes insulin resistance in cells, possibly by entering the hexosamine
      biosynthetic pathway. In neonatal rat cardiomyocytes, glucosamine treatment
      blocked both insulin and ET-1-stimulated glucose uptake and also eliminated the
      translocation of IRAP, an aminopeptidase in GLUT4-containing vesicles, from the
      cytoplasm to the plasma membrane. These results suggest that ET-1-induced glucose
      uptake is independent of its effects on modulating intracellular Ca(2+) and cAMP
      levels, but is likely linked to the hexosamine biosynthetic pathway.

PMID- 12193138
TI  - Endothelin A-receptor blockade in experimental diabetes improves glucose balance
      and gastrointestinal function.
AB  - Secondary complications of diabetes mellitus often involve gastrointestinal
      dysfunction. In the experimental Goto Kakizaki rat, a model of Type II diabetes,
      hyperglycaemia and reduced glucose clearance is associated with elevated plasma
      endothelin (ET)-1 levels and selective decreases in nitric oxide synthase in
      circular muscle, longitudinal muscle and neuronal elements of the
      gastrointestinal tract. Functionally, this is accompanied by decreased nitrergic
      relaxatory responses of jejunal longitudinal muscle to tetrodotoxin-sensitive
      electrical field stimulation. Long-term treatment with a selective ET A-type
      receptor antagonist, markedly reduced hyperglycaemia and restored plasma glucose
      clearance rates towards normal. This was associated with a restoration of N(G)
      nitro-L-arginine methyl ester-sensitive relaxatory responses of jejunal
      longitudinal muscle to electrical field stimulation. The results indicate that
      beneficial effects of ETA receptor blockade on gastrointestinal function may
      result from an improvement in insulin sensitivity with concomitant reduction of
      the severity of hyperglycaemia. ETA receptor blockade may represent a new
      therapeutic principle for improving glucose tolerance in Type II diabetes and
      could be beneficial in alleviating or preventing hyperglycaemia-related secondary
      complications in this condition.

PMID- 12193139
TI  - Oestrogen protects against ischaemic acute renal failure in rats by suppressing
      renal endothelin-1 overproduction.
AB  - We investigated whether the treatment with 17 beta-oestradiol has renal
      protective effects in male rats with ischaemic acute renal failure (ARF). We also
      examined if the effect of 17 beta-oestradiol is accompanied by suppression of
      enhanced endothelin-1 production in postischaemic kidneys. Ischaemic ARF was
      induced by clamping the left renal artery and vein for 45 min followed by
      reperfusion, 2 weeks after contralateral nephrectomy. Renal function parameters
      such as blood urea nitrogen, plasma creatinine and creatinine clearance were
      measured to test the effectiveness of the steroid hormone. Renal function in ARF
      rats markedly decreased 24 h after reperfusion. The ischaemia/reperfusion-induced
      renal dysfunction was dose-dependently improved by pretreatment with 17 beta
      oestradiol (20 or 100 microg/kg, intravenously). Histopathological examination of
      the kidney of untreated ARF rats revealed severe lesions, such as tubular
      necrosis, proteinaceous casts in tubuli and medullary congestion, all of which
      were markedly improved by the higher dose of 17 beta-oestradiol. In addition,
      endothelin-1 content in the kidney after the ischaemia/reperfusion increased
      significantly by approx. 2-fold over sham-operated rats, and this elevation was
      dose-dependently suppressed by the 17 beta-oestradiol treatment. These results
      suggest that oestrogen exhibits protective effects against renal dysfunction and
      tissue injury induced by ischaemia/reperfusion, possibly through the suppression
      of endothelin-1 overproduction in postischaemic kidneys.

PMID- 12193140
TI  - Acute effects of 17 beta-oestradiol on functional activity of endothelin
      converting enzymes in human arteries and veins.
AB  - In this study, we investigated the short-term effect of 17 beta-oestradiol on
      functional enzyme activity (FEA) of endothelin-converting enzymes in vitro using
      human internal mammary arteries (n=7-8) and human saphenous veins (n=16-17)
      obtained from patients undergoing coronary artery bypass graft surgery. Vascular
      rings were preincubated with either solvent control (0.2% ethanol) or 17 beta
      oestradiol (1 microM) for 30 min and concentration-response curves to big ET-1
      (0.1-100 nM) or ET-1 (0.1-100 nM) were performed. FEA for each concentration was
      calculated as the percentage activity [(contraction to big ET-1/contraction to ET
      1)x100] normalized to KCl (100 mM). In control experiments, at low concentrations
      FEA was lower in internal mammary arteries than in saphenous veins (P<0.05).
      While FEA was suppressed in saphenous veins by 10 nM (4+/-1 versus 22+/-5%,
      P<0.01) and 30 nM (26+/-4 versus 48+/-7%, P<0.05) 17 beta-oestradiol, FEA was
      markedly enhanced in internal mammary arteries by 10 nM (33+/-12 versus 1+/-1%,
      P<0.001) and 30 nM (44+/-12 versus 8+/-3%, P<0.01) 17 beta-oestradiol. FEA was
      not affected by 100 nM 17 beta-oestradiol. These results demonstrate for the
      first time that short-term exposure to 17 beta-oestradiol affects FEA in vitro.
      Human internal mammary arteries have lower FEA than the saphenous veins, but FEA
      is differentially affected by acute exposure to 17 beta-oestradiol in human
      arteries and veins. Whether changes in FEA play a role in the vascular effects of
      17 beta-oestradiol in vivo remains to be determined.

PMID- 12193141
TI  - Effect of castration on endothelin receptors.
AB  - Endothelin (ET) plays a pivotal role in the pathogenesis of cell growth disorders
      such as cancer. Atrasentan (ABT-627), a selective antagonist for the ET receptor
      A (ET(A)), has shown benefit in controlling disease progression in men with
      hormone refractory prostate cancer who have undergone aggressive hormone ablation
      therapy. It is not known how hormone ablation affects ET-binding sites, although
      ET-1 and ET(A) expression are found to be elevated in prostate cancer patients.
      In this study, we examined the effect of castration on ET receptor binding in
      male beagle dogs. Three dogs were surgically castrated and another three sham
      operated. The animals were sacrificed 1 week after operation and membranes were
      prepared from the prostate, heart, brain, kidney, liver and lung for ET-1, ET-3
      and angiotensin II (A-II, as a control) binding studies. No significant
      difference in A-II binding was observed between castrated and sham-operated
      animals. However, ET-1 and ET-3 binding to prostate and brain membranes were
      altered significantly. From saturation binding studies using ET-1 in the
      prostate, the K(d) and B(max) values increased from 0.043 nM and 0.094 pmol/mg
      respectively in sham-operated dogs to 0.104 nM and 0.311 pmol/mg respectively in
      castrated animals. These results indicate that surgical castration in dogs
      produces a change in the ET receptor density in the prostate and brain, and may
      have implications for the effect of hormone ablation therapy on ET receptor
      expression in prostate cancer patients.

PMID- 12193142
TI  - Endothelin system in normal and hypertensive pregnancy.
AB  - Pre-eclampsia complicates approximately 5-7% of pregnancies and it may be
      deleterious to both maternal and fetal health. In a prospective study, we
      investigated plasma endothelin (ET)-1 concentration within the 24th and 36th
      gestational week in non-smoking pregnant women. Thirty women fulfilled the
      criteria for the diagnosis of pre-eclampsia according to the American College of
      Obstetricians and Gynaecologists: de novo arterial hypertension after the 20th
      gestational week in at least two separate measurements and proteinuria of more
      than 300 mg/l in a random specimen. For comparison, we analysed blood samples
      from 125 non-pre-eclamptic pregnant women. ET-1 concentrations were higher in pre
      eclamptic pregnancies at both time points (mean+/-S.D.: 1.07+/-2.00 versus 0.54+/
      0.56 pg/ml, P=0.045 at 24th week; 0.75+/-1.20 versus 0.44+/-0.45 pg/ml, P=0.023
      at 36th week). Receiver operating characteristic (ROC) curves revealed a
      significant interaction between ET-1 plasma concentrations at the 36th week and
      the diagnosis of pre-eclampsia [area under the curve (AUC)+/-S.E.M.: 0.657+/
      0.049, P=0.008] and a cut-off value at 0.30 pg/ml. Multivariate analysis showed a
      4.6-fold higher chance (95% confidence interval: 1.7-12.1, P=0.002) for the
      diagnosis of pre-eclampsia in pregnant women with ET-1 plasma concentration
      higher than 0.30 pg/ml at the 36th week. Interaction between ET-1 plasma
      concentration at the 24th week and diagnosis of pre-eclampsia was not significant
      in ROC curve analysis (AUC+/-S.E.M.: 0.594+/-0.071, P=0.278). Interestingly, we
      found a strong positive correlation between ET-1 concentration in the 24th and
      36th week in linear regression analysis in pre-eclamptic (r=0.99, P<0.001) and
      non-pre-eclamptic pregnancies (r=0.61, P<0.001) with a slightly, non-significant
      decrease from the 24th to 36th week (for group means see above), indicating
      individual plasma ET-1 levels even in non-pre-eclamptic pregnancies. Linear
      regression analysis showed no correlation between blood pressure or urine protein
      excretion and ET-1 plasma concentration in non-pre-eclamptic pregnant women. In
      conclusion, our prospective study indicates that the ET system is, in contrast to
      most other forms of human hypertension, activated in pre-eclamptic pregnant
      women.

PMID- 12193143
TI  - Roles of angiogenic factors and endothelin-1 in gastric ulcer healing.
AB  - Endothelins (ETs) participate directly and indirectly in angiogenesis via ET
      receptors. During early fetal angiogenesis, vascular endothelial growth factor
      (VEGF) and its receptors kinase insert domain-containing receptor (KDR) and fms
      like tyrosine kinase-1 (Flt-1) are required for the development of the systemic
      vasculature. In late angiogenesis, stromal-cell-derived factor (SDF-1) and its
      receptor CXC chemokine receptor 4 (CXCR4) act in an organ-specific manner to
      promote the formation and development of large blood vessels supplying the
      gastrointestinal tract. We studied the roles of these ligand receptors in
      angiogenesis during healing of gastric ulcers. We studied the following five
      groups, each consisting of ten cases of endoscopically confirmed gastric ulcer:
      active stage (GA), healing stage (GH) and scar stage (GS) of gastric ulcers
      located in the angulus; Helicobacter pylori (Hp)-positive gastritis (gast+); and
      Hp-negative gastritis (gast-). All cases in the ulcer groups were Hp-positive.
      The study materials consisted of frozen biopsy specimens of lesions arising in
      the angulus. ET-1 was measured by enzyme immunoassay. The other factors were
      assayed by reverse-transcription-PCR. The distributions of ET-1, ETA receptor
      (ETAR), SDF-1 and CXCR4 in the gastric mucosa were evaluated by enzyme
      immunoassay. ET-1 and ETAR reached peak levels during the GH (ET: P<0.05, ETAR:
      P<0.01). VEGF mRNA increased slightly during the GA, but did not differ
      significantly among the groups. KDR and Flt-1 levels were high during the GA, the
      level being significantly higher than those during the GH and GS (P<0.05). SDF-1
      levels significantly decreased during the GH and GS compared with levels during
      the GA, and CXCR4 significantly increased during the GH and GS (P<0.01). On
      immunostaining, ET-1-positive cells and ETAR-positive cells were found in the
      endothelium, vascular smooth muscle and gastric epithelium, and CXCR4-positive
      cells were found in the endothelium and gastric epithelium during the GH and GS.
      Our results suggest that VEGF receptors are mainly expressed early in ulcer
      development and participate in the initial stage of angiogenesis. SDF-1 receptors
      and ETAR are primarily expressed during the GH and GS and are involved in
      vascular maturation and gastric mucosal regeneration during late angiogenesis.

PMID- 12193144
TI  - Effect of aging on gene expression rates of endothelin-1 and endothelin
      2/vasoactive intestinal contractor in ethanol-induced gastric mucosal injury of
      the mouse.
AB  - To elucidate the physiological roles of endothelin-1 (ET-1) and endothelin-2 (ET
      2)/vasoactive intestinal contractor (VIC) in gastric injury of mice, we measured
      the gene expression rates of ET-1 and ET-2/VIC in gastric injury induced by
      ethanol in young (8 weeks) and old (>33 weeks) mice. Mice that were fasted for 24
      h were injected with absolute ethanol intragastrically and killed after 1 or 4 h
      of ethanol exposure. The size of the gastric lesions increased gradually after
      ethanol exposure and was at its greatest after 4 h, in both young and old mice.
      The gene expression of ET-1 tended to increase after 1 h and to decrease by 4 h
      of ethanol exposure in both young and old mice. However, the gene expression of
      ET-2/VIC in young mice increased significantly after 1 and 4 h of ethanol
      exposure, whereas the gene expression of ET-2/VIC in the old mice did not change
      after ethanol exposure. Based on these results, we conclude that aging influences
      the gene expression of ET-2/VIC but not lesion size or gene expression of ET-1 in
      ethanol-induced gastric injury in the mouse. We therefore suggest that regulation
      of gene expression of these two genes differs during the course of aging.

PMID- 12193145
TI  - Reduction of endothelin-1 binding and inhibition of endothelin-1-mediated
      detrusor contraction by naftidrofuryl.
AB  - Endothelin-1 (ET-1) causes urinary bladder smooth muscle contraction and the
      endothelin receptors A and B (ET(A) and ET(B)) are both known to be present in
      the rabbit urinary bladder. Alterations in ET-1 signalling have been implicated
      in the pathophysiology of urinary tract disorders secondary to bladder outlet
      obstruction and also in diabetic cystopathy. Naftidrofuryl (Naf) (marketed under
      the trade name Praxilene) improves walking distance in patients with peripheral
      vascular disease, an effect which may be partially attributed to ET-1 antagonism.
      The purpose of this study is to assess whether Naf will reduce ET-1 binding in
      the rabbit detrusor muscle and to assess whether there is inhibition of ET-1
      mediated detrusor contraction. Detrusor smooth muscle strips were mounted in
      organ baths and cumulative response curves were measured for ET-1-mediated
      contractions in the presence and absence of 10(-6) M Naf (therapeutic
      concentration). In addition, ET-1 was added to the detrusor strips in the
      presence of the ET(A) antagonist, BQ123, and the ET(B) antagonist, BQ788, to
      identify the receptor subtype functionally involved. Overall inhibition of
      [(125)I]ET-1 binding by Naf was assessed using autoradiography. Identification of
      receptor-subtype binding reduction was assessed using the radioligands
      [(125)I]PD151242 and [(125)I]BQ3020. Naf inhibited ET-1-mediated detrusor
      contractions significantly (P<0.04), e.g. at 10(-10) M ET-1, contraction was
      completely abolished by Naf. Autoradiography indicated that Naf competitively
      inhibited [(125)I]ET-1 binding in a dose-dependent manner (IC(50)=3x10(-7) M).
      All radioligand binding was reduced indicating binding of Naf to both ET(A) and
      ET(B) receptors. Naf reduces binding of ET-1 to rabbit detrusor ET(A) and ET(B)
      receptors and inhibits ET-1-induced detrusor contractions mediated by ET(A)
      receptors. Naf may have therapeutic potential in the treatment of bladder
      disorders secondary to bladder outlet obstruction and diabetes mellitus.

PMID- 12193146
TI  - Endothelin-1 production by a microvascular endothelial cell line treated with
      Plasmodium falciparum parasitized red blood cells.
AB  - In this study, we investigated the production of endothelin 1 (ET-1) by a human
      microvascular endothelial cell line, HMEC-1, co-cultured with Plasmodium
      falciparum-parasitized red blood cells (pRBCs). The results indicate that hypoxia
      increased the basal level of ET-1 production by HMEC-1 cells after 24 or 48 h of
      treatment. However, the co-incubation of HMEC-1 cells with pRBCs, but not with
      uninfected RBCs, induced a dose-dependent decrease of both constitutive and
      hypoxia-induced ET-1 production. The inhibition was not due to a decrease in cell
      viability, as lactate dehydrogenase release remained constant. These results
      indicate that pRBCs are able to interfere with both the constitutive and
      stimulated ET-1 release from the microvascular endothelium, thus inducing local
      modifications of the vascular tone and of the inflammatory response. This could
      be of relevance in the pathogenesis of the most severe forms of P. falciparum
      infections, such as cerebral malaria or malaria during pregnancy.

PMID- 12193147
TI  - Effects of head-up tilting on baroreceptor control in subjects with different
      tolerances to orthostatic stress.
AB  - During orthostatic stress, an increase in peripheral vascular resistance normally
      results in arterial blood pressure being well maintained, despite a decrease in
      cardiac output. The present study was undertaken to determine whether the
      sensitivity of the carotid baroreceptor reflex was increased during orthostatic
      stress and whether failure to develop this increase was associated with poor
      orthostatic tolerance. Three groups of subjects were studied: asymptomatic
      controls; patients investigated for suspected posturally related syncope but who
      had normal responses to an orthostatic stress test (normal patients); and
      patients who were shown to have low orthostatic tolerance (early fainters). We
      determined responses of R-R interval and forearm vascular resistance (mean
      arterial pressure/brachial artery velocity by Doppler ultrasonography) to the
      loading and unloading of carotid baroreceptors by application of pressures of -30
      and +30 mmHg to a chamber fitted over the neck. Responses were determined after
      20 min of supine rest and after 10 min of head-up tilt at 60 degrees. Responses
      of cardiac interval were not significantly different between the three groups,
      and they were not altered by the postural change. Vascular responses also did not
      differ between the groups during supine rest. However, in healthy volunteers and
      in normal patients, responses to both neck suction and pressure were
      significantly enhanced during head-up tilt. In controls, responses to suction
      were increased by tilt from 0.04+/-0.1 to -1.01+/-0.2%.mmHg(-1) (means+/-S.E.M.;
      P<0.001) and those to neck pressure from -0.6+/-0.3 to -3.1+/-1.1%.mmHg(-1)
      (P<0.05). In the normal patients, the corresponding changes were: during suction,
      from -0.2+/-0.1 to -0.7+/-0.1%.mmHg(-1) (P<0.05); during pressure, from -0.7+/
      0.1 to -1.5+/-0.3%.mmHg(-1) (P<0.05). In contrast, in patients with low
      orthostatic tolerance, posture had no effect on the reflex (neck suction, from 
      0.3+/-0.1 to -0.3+/-0.1%.mmHg(-1); neck pressure, from -1.0+/-0.3 to -0.9+/
      0.2%.mmHg(-1)). We suggest that an increase in the sensitivity of the carotid
      baroreceptor/vascular resistance reflex may be important in the maintenance of
      blood pressure during orthostatic stress, and that failure of this to occur in
      patients with posturally related syncope may go some way towards explaining their
      poor orthostatic tolerance.

PMID- 12193148
TI  - Measurement of apolipoprotein B-48 in the Svedberg flotation rate (S(f))>400,
      S(f) 60-400 and S(f) 20-60 lipoprotein fractions reveals novel findings with
      respect to the effects of dietary fatty acids on triacylglycerol-rich
      lipoproteins in postmenopausal women.
AB  - The present study was designed to examine whether the type of fat ingested in an
      initial test meal influences the response and density distribution of dietary
      derived lipoproteins in the Svedberg flotation rate (S(f))>400, S(f) 60-400 and
      S(f) 20-60 lipoprotein fractions. A single-blind randomized within-subject
      crossover design was used to study the effects of palm oil, safflower oil, a
      mixture of fish and safflower oil, and olive oil on postprandial apolipoprotein
      (apo) B-48, retinyl ester and triacylglycerol responses in each lipoprotein
      fraction following an initial test meal containing one of the oils and a second
      standardized test meal. For all dietary oils, late postprandial (300 min)
      concentrations of triacylglycerol and apo B-48 were significantly higher in the
      S(f) 60-400 fraction than in the S(f)>400 fraction (P<0.02). Significantly
      greater apo B-48 incremental areas under the curve (IAUCs) were also observed in
      the S(f) 60-400 fraction than in the S(f)>400 fraction following palm oil,
      safflower oil and olive oil (P<0.04), with a similar non-significant trend for
      fish/safflower oil. Olive oil resulted in a significantly greater apo B-48 IAUC
      in the S(f)>400 fraction (P<0.02) than did any of the other dietary oils, as well
      as a tendency for a higher IAUC in the S(f) 60-400 fraction compared with the
      palm, safflower and fish/safflower oils. In conclusion, we have found that the
      majority of intestinally derived lipoproteins present in the circulation
      following meals enriched with saturated, polyunsaturated or monounsaturated fatty
      acids are of the density and size of small chylomicrons and chylomicron remnants.
      Olive oil resulted in a greater apo B-48 response compared with the other dietary
      oils following sequential test meals, suggesting the formation of a greater
      number of small (S(f) 60-400) and large (S(f)>400) apo B-48-containing
      lipoproteins in response to this dietary oil.

PMID- 12193149
TI  - Role of female sex hormones in neuronal nitric oxide release and metabolism in
      rat mesenteric arteries.
AB  - This study examines the effects of female sex hormones on the vasoconstrictor
      response to electrical field stimulation (EFS), as well as the modulation of this
      response by neuronal NO. For this purpose, segments of denuded superior
      mesenteric artery from ovariectomized (OvX) female Sprague-Dawley rats and from
      control rats (in oestrus phase) were used. EFS induced frequency-dependent
      contractions, which were greater in segments from OvX rats than in those from
      control rats. The NO synthase inhibitor N(G)-nitro-l-arginine methyl ester
      strengthened EFS-elicited contractions to a greater extent in arteries from OvX
      rats than in those from control rats. Similar results were observed with the
      preferential neuronal NO synthase inhibitor 7-nitroindazole. The sensorial
      neurotoxin capsaicin did not modify EFS-induced contractions in segments from
      either group. In noradrenaline-precontracted segments, sodium nitroprusside (SNP)
      induced concentration-dependent relaxation, which was greater in segments from
      control rats than in those from OvX rats. 8-Bromo-cGMP induced similar
      concentration-dependent relaxation in noradrenaline-precontracted segments from
      both OvX and control rats. Diethyldithiocarbamate, a superoxide dismutase (SOD)
      inhibitor, reduced the relaxation induced by SNP in segments from both groups of
      rats. SOD, a superoxide anion scavenger, enhanced the relaxation induced by SNP
      in segments from OvX rats, but did not modify it in segments from control rats.
      EFS induced NO(-)(2) formation, which was greater in segments from OvX than in
      those from control rats, and pretreatment with tetrodotoxin, a blocker of nerve
      impulse propagation, abolished release in both cases. These results suggest that
      EFS induces greater neuronal NO release in mesenteric segments from OvX rats than
      in those from control rats and, although NO metabolism is also higher, the
      contribution of net neuronal NO in the vasomotor response to EFS is greater in
      segments from OvX rats than in those from control rats.

PMID- 12193150
TI  - Left ventricular long-axis diastolic function is augmented in the hearts of
      endurance-trained compared with strength-trained athletes.
AB  - In order to determine left ventricular global and regional myocardial functional
      reserve in endurance-trained and strength-trained athletes, and to identify
      predictors of exercise capacity, we studied 18 endurance-trained and 11 strength
      trained athletes with left ventricular hypertrophy (172+/-27 and 188+/-39 g/m(2)
      respectively), and compared them with 14 sedentary controls. Global systolic
      (ejection fraction) and diastolic (transmitral flow) function, and regional
      longitudinal and transverse myocardial velocities [tissue Doppler
      echocardiography (TDE)], were measured at rest and immediately after exercise. In
      endurance-trained compared with strength-trained athletes, resting heart rate was
      lower (59+/-11 and 76+/-9 beats/min respectively; P<0.001), and the increase at
      peak exercise was greater (+211% and +139% respectively; P<0.001). In addition,
      exercise duration, workload, maximal oxygen consumption and global systolic
      functional reserve (but not peak ejection fraction) were higher in the endurance
      trained athletes, and resting global diastolic function (E/A ratio 1.62+/-0.40
      compared with 1.18+/-0.23; P<0.01) (where E-wave is peak velocity of early
      diastolic mitral inflow and A-wave is peak velocity of mitral inflow during
      atrial contraction) and long-axis diastolic velocities (E(TDE)/A(TDE) ratio 2.2+/
      1.2 compared with 1.1+/-0.3; P<0.01) (where E(TDE) and A(TDE) represent peak
      early- and late-diastolic myocardial or tissue velocity respectively) were
      augmented. Systolic velocities were similar. Exercise capacity was best predicted
      from end-diastolic diameter index and E/A ratio at rest, and end-diastolic volume
      index and diastolic longitudinal velocity during exercise (r=0.74, n=43,
      P<0.001). In conclusion, endurance-trained athletes had higher left ventricular
      long-axis diastolic velocities, augmented global early diastolic filling, and
      greater chronotropic and global systolic functional reserve. Maximal oxygen
      consumption was determined by diastolic loading and early relaxation rather than
      by systolic function, suggesting that dynamic exercise training improves cardiac
      performance by an effect on diastolic filling.

PMID- 12193151
TI  - Genetic contribution to renal function and electrolyte balance: a twin study.
AB  - A classical twin study was performed to assess the relative contributions of
      genetic and environmental factors to serum levels of calcium, phosphate and
      magnesium, urinary levels of calcium, sodium and potassium, and creatinine
      clearance. The subjects were 1747 adult female twin pairs: 539 monozygotic and
      1208 dizygotic. The intraclass correlations were calculated, and maximum
      likelihood model fitting was used to estimate genetic and environmental variance
      components. The intraclass correlations for all of the variables assessed were
      higher in monozygotic twin pairs. The heritabilities (with 95% confidence
      intervals) obtained from model fitting were: serum calcium, 33% (21-45%); serum
      phosphate, 58% (53-62%), serum magnesium, 27% (15-39%); 24 h urinary potassium,
      40% (27-51%); 24 h urinary calcium, 52% (41-61%); 24 h urinary sodium, 43% (30
      54%); fractional excretion of sodium, 52% (44-59%); serum creatinine, 37% (25
      49); calculated creatinine clearance, 63% (54-72%). This study provides evidence
      for the importance of genetic factors in determining urinary and blood levels of
      the major electrolytes involved in blood pressure regulation. Identifying
      heritability is the first step on the way to finding specific genes, which may
      improve our insight into the pathophysiology of the metabolism of these
      electrolytes, and thereby improve our understanding of the aetiology of complex
      diseases such as renal failure and hypertension.

PMID- 12193152
TI  - Altered cutaneous microvascular responses to reactive hyperaemia in coronary
      artery disease: a comparative study with conduit vessel responses.
AB  - Cutaneous microvascular responses to physiological stimuli are currently being
      investigated as indices of vascular function and to monitor responses to therapy.
      We attempted to systematically assess various microvascular cutaneous flow
      indices in response to reactive hyperaemia in control subjects and in patients
      with coronary artery disease (CAD), and to correlate these with brachial artery
      flow-mediated dilation (FMD). Groups of 24 healthy controls and 24 subjects with
      CAD underwent sequential brachial FMD determination in the dominant arm, and
      laser Doppler imaging to assess skin blood flow in the contralateral arm in
      response to reactive hyperaemia induced by cuff inflation and release. Laser
      Doppler values were expressed as: (a) AUC(5 min) (area under the curve over 5 min
      of release), (b) time to peak response, (c) % reactive hyperaemia, and (d) peak
      perfusion ratio. As expected, FMD was attenuated in CAD patients compared with
      controls (1.85+/-4.29% compared with 4.30+/-4.00%; P=0.05). Percentage reactive
      hyperaemia (CAD, 294+/-290%; controls, 501+/-344%; P=0.04) and the time to peak
      response as measured by laser Doppler imaging (CAD, 16.84+/-9.61 s; controls,
      9.13+/-4.43 s; P=0.001) were significantly different between the CAD and control
      groups, while AUC(5 min) and the peak perfusion ratio did not show significant
      differences. Receiver operator curves for sensitivity/specificity analysis
      suggested that the time to peak response derived by laser Doppler imaging was
      superior to FMD for the diagnosis of CAD, with an overall specificity of 91.3%
      (positive predictive value of 89.4%) and a sensitivity of 73.7% (negative
      predictive value of 77.6%). In conclusion, laser Doppler-derived indices of
      microvascular flow do not correlate with conduit vessel responses. However, a
      time to peak response of >10 s as measured by laser Doppler imaging offers
      superior specificity for the diagnosis of CAD compared with brachial FMD.

PMID- 12193153
TI  - Erythropoietin and the brain: from neurodevelopment to neuroprotection.
AB  - It is now widely known that erythropoietin (Epo) does not only affect the
      haematopoietic system, but it can be considered a multifunctional trophic factor
      with an effect on the general homoeostasis of the entire organism. The recent
      discovery of a specific Epo/Epo-receptor system in the central nervous system
      (CNS) and cerebrospinal fluid, independently of the haematopoietic system, has
      further paved the way for new studies aimed at investigating the different sites
      of cerebral expression of Epo and its receptor, the regulation of their
      expression and, finally, the effects that this hormone has on the development and
      maturation of the brain. A further aim has been to investigate how it influences
      CNS homoeostasis and neurotransmission in adult brain. Attention has also been
      focused on the neurotrophic and neuroprotective function of Epo in different
      conditions of neuronal damage, such as hypoxia, cerebral ischaemia and
      subarachnoid haemorrhage, and therefore on the possibility that human recombinant
      Epo therapy could soon be used in clinical practice, also to limit neuronal
      damage induced by these diseases.

PMID- 12193154
TI  - Myocardial abnormalities in hypertensive patients with normal and abnormal left
      ventricular filling: a study of ultrasound tissue characterization and strain.
AB  - Abnormal left ventricular (LV) filling is common, but not universal, in
      hypertensive LV hypertrophy (LVH). We sought to elucidate the relative
      contributions of myocardial structural changes, loading and hypertrophy to LV
      dysfunction in 113 patients: 85 with hypertensive LVH and 28 controls without LVH
      and with normal filling. Patients with normal dobutamine stress echocardiography
      and no history of coronary artery disease were selected, in order to exclude a
      contribution from ischaemia or scar. Abnormal LV filling was identified in 65 LVH
      patients, based on Doppler measurement of transmitral filling and annular
      velocities. All patients underwent grey-scale and colour tissue Doppler imaging
      from three apical views, which were stored and analysed off line. Integrated
      backscatter (IB) and strain rate imaging were used to detect changes in structure
      and function; average cyclic variation of IB, strain rate and peak systolic
      strain were calculated by averaging each segment. Calibrated IB intensity,
      corrected for pericardial IB intensity, was measured in the septum and posterior
      wall from the parasternal long-axis view. Patients with LVH differed
      significantly from controls with respect to all backscatter and strain
      parameters, irrespective of the presence or absence of abnormal LV filling. LVH
      patients with and without abnormal LV filling differed with regard to age, LV
      mass and incidence of diabetes mellitus, but also showed significant differences
      in cyclic variation (P<0.01), calibrated IB in the posterior wall (P<0.05) and
      strain rate (P<0.01), although blood pressure, heart rate and LV systolic
      function were similar. Multivariate logistic regression analysis demonstrated
      that age, LV mass index and calibrated IB in the posterior wall were independent
      determinants of abnormal LV filling in patients with LVH. Thus structural and
      functional abnormalities can be detected in hypertensive patients with LVH with
      and without abnormal LV filling. In addition to age and LVH, structural (not
      functional) abnormalities are likely to contribute to abnormal LV filling, and
      may be an early sign of LV damage. IB is useful for the detection of myocardial
      abnormalities in patients with hypertensive LVH.

PMID- 12193155
TI  - Forearm elevation augments sympathetic activation during handgrip exercise in
      humans.
AB  - Although angina pectoris in patients with coronary heart disease often occurs
      when their forearms are in an elevated position for a prolonged period, and
      sympathetic activation is a major cause of this condition, little is known about
      the physiological effects of forearm elevation on sympathetic activity during
      forearm exercise. We hypothesized that forearm elevation augments sympathetic
      activation during the static handgrip exercise in humans. A total of 10 healthy
      male volunteers performed 2 min of static handgrip exercise at 30% of maximal
      voluntary contraction followed by 2 min of post-exercise muscle ischaemia (PEMI;
      specific activation of the muscle metaboreflex) with two forearm positions: the
      exercising forearm was elevated 50 cm above the heart (forearm-elevated trial) or
      fixed at the level of the heart (heart-level trial). Muscle sympathetic nerve
      activity (MSNA), blood pressure and heart rate were monitored. MSNA increased
      during handgrip exercise in both forearm positions (P<0.001); the increase was
      51% greater in the forearm-elevated trial (516+/-99 arbitrary units) than in the
      heart-level trial (346+/-44 units; P<0.05). The increase in mean blood pressure
      was 8.4 mmHg greater during exercise in the forearm-elevated trial (P<0.05),
      while changes in heart rate were similar in both forearm positions. The increase
      in MSNA during PEMI was 71% greater in the forearm-elevated trial (393+/-71
      arbitrary units/min) than in the heart-level trial (229+/-29 units/min; P<0.05).
      These results support the hypothesis that forearm elevation augments sympathetic
      activation during handgrip exercise. The excitatory effect of forearm elevation
      on exercising MSNA may be mediated primarily by increased activation of the
      muscle metaboreflex.

PMID- 12193156
TI  - Genetic variation at the interleukin-1 locus is a determinant of changes in
      soluble endothelial factors in patients with acute coronary syndromes.
AB  - Acute coronary syndromes (ACSs) are associated with both systemic inflammatory
      activation and endothelial cell activation, and both of these are linked to
      patient outcome. Genetic variation at the interleukin-1 (IL-1) locus influences
      the clinical patterns of inflammatory disease. We therefore examined the
      association between IL-1 gene polymorphisms and levels of systemic inflammatory
      activation markers [C-reactive protein (CRP) and IL-1 receptor antagonist (IL
      1ra)] and of soluble endothelial activation markers [von Willebrand factor (vWF)
      and E-selectin], in a cohort of 63 patients presenting with non-ST-elevation ACS.
      The IL-1 locus did not significantly influence any of the markers studied at 24 h
      after presentation. Associations of IL-1 polymorphisms with the changes (Delta)
      in CRP, IL-1ra, E-selectin and vWF levels between 24 and 48 h were examined in
      later studies. Delta CRP and Delta IL-1ra showed no significant association with
      any of the polymorphisms studied. There was a strong association between carriage
      of the rare allele (allele 2) of the intron 2 variable number of tandem repeats
      polymorphism of IL-1RN (designated IL-1RN*2) and Delta E-selectin levels:
      [carriage of *2, 3.03 ng/ml [95% confidence interval (CI) 6.26 to 1.51 ng/ml];
      non-carriage of *2, 0.12 ng/ml (95% CI 1.07 to -1.76 ng/ml); P=0.0016], and also
      between carriage of IL-1RN*2 and Delta vWF levels [carriage of *2, 0.78 i.u./ml
      (95% CI 0.96 to 0.44 i.u./ml); non-carriage of *2, 0.1 i.u./ml (95% CI 0.19 to 
      0.1 i.u./ml); P=0.0003]. A composite analysis consisting of carriage of IL-1RN*2
      and the genotype at position -511 in the IL-1B gene suggests the existence of
      haplotypes that influence Delta vWF and Delta E-selectin in patients with ACS.
      Carriage of IL-1RN*2 was also associated with a 2-fold increased likelihood of a
      troponin-positive status compared with non-carriage (P=0.0385). These data
      indicate that, in the setting of non-ST-elevation ACS, genetic variation at the
      IL-1 gene locus contributes to the changes in soluble markers of endothelial
      inflammation.

PMID- 12193157
TI  - Effects of the protein kinase C beta inhibitor LY333531 on neural and vascular
      function in rats with streptozotocin-induced diabetes.
AB  - Elevated protein kinase C activity has been linked to the vascular and neural
      complications of diabetes. The aim of the present study was to examine the
      involvement of the beta-isoform of protein kinase C in abnormalities of neuronal
      function, neural tissue perfusion and endothelium-dependent vasodilation in
      diabetes, by treatment with the selective inhibitor LY333531 (10 mg.kg(-1).day(
      1)). Diabetes was induced in rats by streptozotocin; the duration of diabetes was
      8 weeks. Nerve conduction velocity was monitored, and responses to noxious
      mechanical and thermal stimuli were estimated by the Randall-Sellito and
      Hargreaves tests respectively. Sciatic nerve and superior cervical ganglion blood
      flow were measured by microelectrode polarography and hydrogen clearance.
      Vascular responses were examined using the in vitro mesenteric bed preparation.
      An 8-week period of diabetes caused deficits in sciatic motor (20%) and saphenous
      nerve sensory (16%) conduction velocity, which were reversed by LY333531.
      Diabetic rats had mechanical and thermal hyperalgesia. LY333531 treatment did not
      affect mechanical thresholds, but corrected thermal hyperalgesia. Sciatic nerve
      and superior cervical ganglion blood flow were both reduced by 50% by diabetes;
      this was almost completely corrected by 2 weeks of LY333531 treatment. Diabetes
      caused a 32% reduction in vasodilation of the mesenteric vascular bed in response
      to acetylcholine, mediated by nitric oxide and endothelium-derived
      hyperpolarizing factor. When the former was abolished during nitric oxide
      synthase inhibition, an 80% diabetic deficit in the remaining relaxation was
      noted. LY333531 treatment attenuated the development of these defects by 64% and
      53% respectively. Thus protein kinase C beta contributes to the neural and
      vascular complications of experimental diabetes; LY333531 is a candidate for
      further study in clinical trials of diabetic neuropathy and vasculopathy.

PMID- 12193158
TI  - New hope for the treatment of diabetic complications.

PMID- 12193159
TI  - Hyperglycaemia suppresses the secretion of ghrelin, a novel growth-hormone
      releasing peptide: responses to the intravenous and oral administration of
      glucose.
AB  - Ghrelin is a novel growth hormone (GH)-releasing peptide, isolated from the
      stomach, which may also cause a positive energy balance by stimulating food
      intake and reducing fat utilization. However, whether glucose influences the
      release of ghrelin remains unknown. Accordingly, we examined circulating levels
      of ghrelin and GH in response to the intravenous or oral administration of 50 g
      of glucose in eight healthy humans. After the administration of intravenous
      glucose (50 g), the plasma ghrelin level decreased significantly from 127+/-9 to
      98+/-9 fmol/ml (P<0.01), associated with an increase in plasma glucose from 85+/
      3 to 357+/-19 mg/dl (P<0.01). Ingestion of 50 g of glucose decreased the plasma
      ghrelin level significantly from 134+/-12 to 97+/-15 fmol/ml (P<0.01), associated
      with an increase in plasma glucose from 93+/-3 to 166+/-10 mg/dl (P<0.01). The
      decrease in the plasma ghrelin level lasted for more than 30 min after recovery
      of the plasma glucose level. In conclusion, ghrelin secretion may be suppressed,
      at least in part, by an increased plasma glucose level in healthy humans.

PMID- 12193160
TI  - Ghrelin: sweet regulation?

PMID- 12193161
TI  - Oxidative damage and phospholipid fatty acyl composition in skeletal muscle
      mitochondria from mice underexpressing or overexpressing uncoupling protein 3.
AB  - Five markers of different kinds of oxidative damage to proteins [glutamic
      semialdehyde, aminoadipic semialdehyde, N (epsilon)-(carboxymethyl)lysine, N
      (epsilon)-(carboxyethyl)lysine and N (epsilon)-(malondialdehyde)lysine] and
      phospholipid fatty acyl composition were identified and measured in skeletal
      muscle mitochondria isolated from mice genetically engineered to underexpress or
      overexpress uncoupling protein 3 (UCP3). Mitochondria from UCP3-underexpressing
      mice had significantly higher levels of oxidative damage than wild-type controls,
      suggesting that UCP3 functions in vivo as part of the antioxidant defences of the
      cell, but mitochondria from UCP3-overexpressing mice had unaltered oxidative
      damage, suggesting that mild uncoupling in vivo beyond the normal basal
      uncoupling provides little protection against oxidative stress. Mitochondria from
      UCP3-underexpressing mice showed little change, but mitochondria from UCP3
      overexpressing mice showed marked changes in mitochondrial phospholipid fatty
      acyl composition. These changes were very similar to those previously found to
      correlate with basal proton conductance in mitochondria from a range of species
      and treatments, suggesting that high protein expression, or some secondary result
      of uncoupling, may cause the observed correlation between basal proton
      conductance and phospholipid fatty acyl composition.

PMID- 12193162
TI  - Solution structure and topology of the N-terminal membrane anchor domain of a
      microsomal cytochrome P450: prostaglandin I2 synthase.
AB  - The three-dimensional structure of a synthetic peptide corresponding to the N
      terminal membrane anchor domain (residues 1-25) of prostaglandin I(2) synthase
      (also known as cytochrome P450 8A1), an eicosanoid-synthesizing microsomal
      cytochrome P450, has been determined by two-dimensional (1)H NMR spectroscopy in
      trifluoroethanol and dodecylphosphocholine which mimic the hydrophobic membrane
      environment. A combination of two-dimensional NMR experiments, including NOESY,
      TOCSY and double-quantum-filtered COSY, was used to obtain complete (1)H NMR
      assignments for the peptide. Using the NOE data obtained from the assignments and
      simulated annealing calculations, the N-terminal membrane domain reveals a bent
      shaped structure comprised of an initial helix (residues 3-11), followed by a
      turn (residues 12-16) and a further atypical helix (residues 17-23). The
      hydrophobic side chains of the helix and turn segments (residues 1-20) are
      proposed to interact with the hydrocarbon interior of the phospholipid bilayer of
      the endoplasmic reticulum (ER) membrane. The hydrophilic side chains of residues
      21-25 (Arg-Arg-Arg-Thr-Arg) point away from the hydrophobic residues 1-20 and are
      expected to be exposed to the aqueous environment on the cytoplasmic side of the
      ER membrane. The distance between residues 1 and 20 is approx. 20 A (1 A=0.1 nm),
      less than the thickness of a lipid bilayer. This indicates that the N-terminal
      membrane anchor domain of prostaglandin I(2) synthase does not penetrate the ER
      membrane.

PMID- 12193164
TI  - Influences on adolescent smoking behaviour: siblings' smoking and norms in the
      social environment do matter.
AB  - The prevalence of smoking among adolescents has stopped declining in spite of all
      preventative efforts. There is a need for further knowledge and understanding of
      why adolescents initiate and continue tobacco use. The aim of the present study
      was to investigate important facets of adolescents' tobacco use, such as their
      reasons for smoking, and their smoking patterns in relation to smoking habits in
      the family and the social environment. This study was part of a larger one that
      used a descriptive, cross-sectional design with questionnaires to 216 pupils in
      grade 5 (11 years of age) and 225 pupils in grade 8 (14 years of age) in a south
      western county in Sweden. Thirteen per cent of the pupils in grade 8 were regular
      tobacco users. Smoking habits by relatives, especially siblings, influenced
      tobacco use by adolescents. An association was found between smoking by
      adolescents and mother's employment, and between the smoking status of girls and
      family status. The pupils valued their parents' opinions, and wanted parents and
      other adults to take a clear stand against tobacco. The present study reinforces
      the importance of norm setting by parents and siblings for adolescents' tobacco
      use. Preventive measures may be more appropriately directed towards those with
      the highest risks, i.e. pupils with smoking siblings and smoking peers.

PMID- 12193163
TI  - Bax oligomerization in mitochondrial membranes requires tBid (caspase-8-cleaved
      Bid) and a mitochondrial protein.
AB  - In response to various apoptotic stimuli, Bax, a pro-apoptotic member of the Bcl
      2 family, is oligomerized and permeabilizes the mitochondrial outer membrane to
      apoptogenic factors, including cytochrome c. Bax oligomerization can also be
      induced by incubating isolated mitochondria containing endogenous Bax with
      recombinant tBid (caspase-8-cleaved Bid) in vitro. The mechanism by which Bax
      oligomerizes under these conditions is still unknown. To address this question,
      recombinant human full-length Bax was purified as a monomeric protein. Bax failed
      to oligomerize spontaneously in isolated mitochondria or in liposomes composed of
      either cardiolipin or lipids extracted from mitochondria. However, in the
      presence of tBid, the protein formed large complexes in mitochondrial membranes
      and induced the release of cytochrome c. tBid also induced Bax oligomerization in
      isolated mitochondrial outer membranes, but not in other membranes, such as
      plasma membranes or microsomes. Moreover, tBid-induced Bax oligomerization was
      inhibited when mitochondria were pretreated with protease K. The presence of the
      voltage-dependent anion channel was not required either for Bax oligomerization
      or for Bax-induced cytochrome c release. Finally, Bax oligomerization was
      reconstituted in proteoliposomes made from mitochondrial membrane proteins. These
      findings imply that tBid is necessary but not sufficient for Bax oligomerization;
      a mitochondrial protein is also required.

PMID- 12193165
TI  - Informal care: the views of people receiving care.
AB  - Informal care is perceived to be the best option for people who require
      assistance to look after themselves. National and international studies of
      informal care have focused on the carer, not on the care provided, or the needs
      and experiences of the care recipients. In the present study, 55 people receiving
      informal care (21 males and 24 females, mean age = 67.6) were surveyed to
      determine the type of assistance that they receive, perceptions of the quality of
      their care, feelings about being looked after by a carer and their perceptions of
      the services which would be useful. A random sample of 531 households were
      selected as part of a larger study into informal care in the west of Ireland. A
      total of 98 carers were identified and 55 of the people they looked after were
      well enough to participate in the study. Over two-thirds of carers assisted with
      household chores (e.g. cleaning, preparing meals and shopping). Other activities
      which carers assisted with included keeping the person safe from household
      accidents (62%), personal care (42%), and dressing and undressing (31%). Whilst
      most were very satisfied with the quality of care, a minority reported
      dissatisfaction, and stated that their carer showed signs of anger and
      frustration. Common concerns related to the health of the carer, their safety
      when the carer is not available and the cost of being cared for. Financial
      support for the person receiving care and the carer were the main priorities for
      these individuals. The present study points to a need for greater involvement of
      care recipients in planning services relating to informal care, and support and
      access to health professionals for people receiving care. People receiving care
      are also concerned about the level of financial support for themselves and their
      carers.

PMID- 12193166
TI  - 'Like a friend going round': reducing the stigma attached to mental healthcare in
      rural communities.
AB  - Traditionally, stigma is seen as something that is the fault of the mental health
      system, and that involves an individual suffering social disapprobation and
      reduced life chances as a result of having been given a diagnostic label and an
      identity as a patient as a result of their contact with psychiatric institutions.
      The present study, based on focus group discussions conducted with users and
      mental healthcare workers in a rural setting, suggests that this classic
      conception of stigma does not readily apply to care in the community. First,
      workers described themselves as actively trying to challenge stigma at an
      institutional level, as well as being apt to change their own practice to reduce
      the stigmatizing effect of mental healthcare on their clients and make their
      presence less conspicuous. The ideal was to be 'like a friend going round'.
      However, this view included a somewhat passive notion of clients. By contrast,
      the present investigation showed that clients described themselves in much more
      active terms as being aware of possible sources of stigma and being inclined to
      challenge negative attitudes themselves. Future mental healthcare practice could
      draw upon professionals' stock of knowledge as to how their practice could lead
      to less stigma and could build upon clients' own strengths to achieve stigma
      reduction.

PMID- 12193167
TI  - Drawing the line: the boundaries of volunteering in the community care of older
      people.
AB  - Volunteers can play important roles in the provision of support and care to frail
      or confused older people living in their own homes. There are conflicting
      expectations as to what these roles should be since there are unclear boundaries
      with those of paid care and with informal care. The present article explores some
      of these boundaries, drawing on material from a study of 14 volunteer schemes in
      England. The aim of the research was to explore the roles played by volunteers in
      the overall care division of labour. The main method used was that of
      semistructured interviews with organizers and volunteer coordinators of the
      schemes involved. The findings presented here relate to the limitations on the
      type of cases taken on, and to the boundaries with professional care, paid manual
      work and informal care. It concludes that the ways in which these boundaries are
      established and maintained depends not only on legal and policy constraints at
      the level of the state, but also on negotiation between organizations and
      individuals at a local level. The issues raised are of importance not only to
      research in the area, but to anyone planning similar schemes in the future.

PMID- 12193168
TI  - Inequalities in access to healthcare faced by women who are deaf.
AB  - The Cheshire Deaf Women's Health Project undertook a research study to assess the
      access to healthcare of women who are deaf in Cheshire, UK. Group discussions
      took place with 13 women who were hard of hearing and 14 women who were Deaf Sign
      Language users. Questionnaires were distributed to a stratified random sample of
      103 women taken from the social services register, 38 of which were returned. In
      order to reach more women whose first language was British Sign Language, 129
      questionnaires were distributed to the leaders of various clubs and organizations
      for people who are deaf, and 100 of these were returned. The data revealed
      inequities in access to healthcare. For example, women who are deaf face a lack
      of awareness by health staff of how to communicate with them. The survey
      confirmed that these problems are of major importance to the majority of women
      who are deaf. For example, fewer than one in 10 deaf women said that they usually
      fully understand what the doctor says to them when they visit the doctor on their
      own. There are many other difficulties faced by women who are deaf, leading to
      inequalities when they are compared with hearing people. Almost half the
      respondents said that they would be more likely to use health services if help
      and/or services for deaf women were available. The introduction of various
      relatively simple measures would greatly help to reduce the inequalities of
      access to healthcare faced by deaf women. Under the terms of the Disability
      Discrimination Act 1995, such action is essential if providers are to avoid
      facing possible legal action.

PMID- 12193169
TI  - Focusing upon children and men in situations of domestic violence: an analysis of
      the gendered nature of British health visiting.
AB  - Despite considerable feminist critiques of British health visiting work which
      have pointed to its gendered nature, this issue has received very little
      attention within the professional literature. The emphasis has been upon the
      'health' focus, often highlighting the needs of marginalized groups. The recent
      professional interest in women experiencing domestic violence draws upon a long
      standing feminist concern which has established the extent and nature of domestic
      violence, and the difficulties facing women in seeking help about their
      situation. The present paper reports some findings from a study of British health
      visiting practice in relation to women experiencing domestic violence. Drawing
      upon interview data from 24 health visitors, this paper focuses specifically upon
      health visitors' accounts of their practice in relation to both children and men
      when they were aware women were experiencing domestic violence. Their concerns,
      which include child welfare and personal safety illustrate some of the
      complexities facing practitioners when faced with domestic violence situations.
      The analysis also highlights the gendered practices inherent within health
      visiting work.

PMID- 12193170
TI  - Learning about interagency collaboration: trialling collaborative projects
      between hospitals and community health services.
AB  - Interagency collaboration has increasingly been viewed as an important strategy
      to encourage the co-ordination of healthcare. It is seen to have a number of
      positive outcomes, including: improved service delivery for people requiring
      multiple services; more efficient use of healthcare resources; and a means for
      managers to share the responsibility of community care and reduce organizational
      stress caused by pressures of increasing demand for services within a climate of
      cost containment. However, establishing collaborative interagency relationships
      can be a challenging, long-term and complex process. The present article
      describes some of the findings of a research project that evaluated collaborative
      strategies adopted and trialed by a group of four publicly funded healthcare
      agencies in the southern metropolitan area of Adelaide, South Australia. Key
      findings from the literature about the factors supporting and impeding
      collaboration are discussed in the light of some of the findings from the
      evaluation project. Some of the themes emerging from the Adelaide study include:
      the need for resources for change; experience of multidisciplinary work;
      professional barriers to collaboration; the importance of agreed aims, agendas
      and project ownership; and the importance of supportive leadership. This article
      concludes with a discussion of the difficulties and opportunities for
      collaboration between community-based primary healthcare agencies and acute care
      hospitals. The development of partnerships which are either based on trust, or on
      the open negotiation of power differences and professional territories, and the
      management of mistrust are found to be important foundations for achieving
      greater genuine collaboration between primary and tertiary level healthcare.

PMID- 12193171
TI  - Users' perceptions of an African and Caribbean mental health resource centre.
AB  - It has been suggested that well-documented differences in African and African
      Caribbean people's contact with mental health services may stem from a spiral of
      disaffection, reluctance to seek help and re-admission to hospital in times of
      crisis. In 1997, an African and Caribbean mental health resource centre was
      established in the London borough of Kensington and Chelsea with the aim of
      ensuring that the needs of this group were better met. As part of an evaluation
      of the study, interviews were carried out with 26 clients of the resource centre.
      This article presents their perceptions of the service provided and its impact on
      their lives. The clients' accounts indicate that the resource centre was
      providing a valued service that was successful in reducing their sense of social
      isolation, enabling them to address issues of identity and self-worth associated
      with racism and working with other service providers to better meet their needs.

PMID- 12193172
TI  - Social control agents or front-line carers for people with mental health
      problems: police and mental health services in Sydney, Australia.
AB  - The relationship between mental health services and police and people who have
      mental health problems, are suicidal or are drug- and/or alcohol-affected is
      examined in this paper. A survey of 131 police officers in Sydney, Australia,
      revealed that more than 10% of police time is spent dealing with people with
      mental health problems. Nevertheless, police felt unsupported in this role,
      unprepared for it and torn between the competing demands experienced in their
      work. A lack of confidence in dealing with suicidal people and a belief that work
      with mentally disturbed people does not constitute valid police work are also
      reported. Managing people with mental disturbance is a major concern for police.
      Specifically, there are difficulties relating to: inadequate training and
      education; deficiencies in services/resources; time and resource over
      utilization; communication, liaison and feedback problems, and frustration
      related to accessing mental health facilities/services. It is argued that police
      work involving mentally disturbed people is a valid and necessary role that
      complements law enforcement. In order to facilitate this aspect of police work,
      recommendations are made regarding education and collaborative working
      relationships between police and mental health professionals, which, in turn,
      could improve the care of mentally disturbed people in the community.

PMID- 12193173
TI  - Reluctant empiricists: community mental health nurses and the art of evidence
      based praxis.
AB  - The National Service Framework for Mental Health (1999) emphasizes the need for a
      culture of evidence-based practice (EBP) in mental health care. However, there is
      relatively little research addressing EBP from the perspective of community
      mental health nurses and we are still unsure of why the uptake of this style of
      working has been slow. This paper suggests that rather than thinking in terms of
      'barriers' to the uptake of EBP, the issue may best be conceptualized as a form
      of praxis on the part of nurses, as they seek to manage the diversity of
      ideologies and practices in their working lives. From an interview and focus
      group study, we identify how practitioners' narrow definition of EBP itself,
      their formulation of how EBP was at odds with the nurse's professional activity
      and the organizational constraints within which they work were perceived to
      inhibit access to information and offer little time and managerial support for
      information seeking. Those who attempt to further the involvement of community
      mental health staff in EBP will have to reconceptualize the reasons why staff
      have yet to incorporate it fully, and acknowledge that this does not occur
      because staff are simply 'ignorant Luddites', but that this resistance enables
      them to retain a sense of control over their working lives and retain a focus on
      work with clients. Future EBP initiatives will have to address these ideological
      and organizational factors in order for uptake to be accelerated. This may
      involve changing organizational cultures and work roles and even encouraging
      activism on the part of the practitioners so as to enable them to learn from each
      other and educate and change their work environments.

PMID- 12193175
TI  - New genomic avenues in behavioural neuroendocrinology.
AB  - Neuroendocrine systems play a key role not only in the maintenance of whole-body
      homeostasis but also as the link between behavioural, endocrine and autonomic
      responses to environmental stimuli. It is becoming increasingly clear that
      neuroendocrine regulatory mechanisms are under the control of a combination of
      factors including genetic background, environment and early-life programming.
      Patterns of gene expression are increasingly being used to provide information on
      the genotypes associated with particular behaviours, and modulation of specific
      parts of the genome allow investigation of the contribution of particular genes.
      The sequencing of the genome provides a unique opportunity to elucidate the
      genetic contribution to neuroendocrine and behavioural processes, and to
      investigate the interactions between genetic and environmental factors. Although
      drugs can be used to activate or inhibit neurotransmitters and receptors, they
      lack specificity. New technologies now permit the activation or inactivation of
      both neurotransmitters and receptors in specific areas of the brain for defined
      periods, including crucially important developmental windows when activation
      appears to have long-term consequences. The future challenges are to define the
      critical mechanisms through which the genetic constitution of an individual human
      or experimental animal interacts with environmental cues to result in altered
      physiological or even pathological behaviour and endocrine function.

PMID- 12193176
TI  - Genes controlling hypothalamic development and sexual differentiation.
AB  - Steroid hormones dramatically influence the development of numerous sites in the
      nervous system. Basic mechanisms in neural development provide foci for
      understanding how factors related to sex can alter the ontogeny of these regions.
      Sex differences in neurogenesis, cell migration, cell differentiation, cell
      death, and synaptogenesis are being addressed. Any and all of these events serve
      as likely targets for genetic or gonadal steroid-dependent mechanisms throughout
      development. Although the majority of sexually dimorphic characteristics in brain
      have been described in older animals, many hormonal mechanisms that determine
      sexually differentiated brain characteristics occur during critical perinatal
      periods. Genes suggested to contribute to the development of specific
      hypothalamic nuclear groups have rarely been examined in the context of sex. The
      identification of sex differences in the expression of some of these genes may
      suggest early and likely transient molecular events that set the stage for later
      amplification by hormone actions. Sex differences in the positioning of cells in
      the developing hypothalamus further suggest that cell migration may be one key
      target for early gene actions that impact long-term susceptibility to brain
      sexual differentiation.

PMID- 12193177
TI  - Metabolic signals, hormones and neuropeptides involved in control of energy
      balance and reproductive success in hamsters.
AB  - In the 'postgenome era', most research on the neuroendocrine control of energy
      homeostasis has focused on hormonal and neuropeptide control of food intake (i.e.
      the amount of food eaten) in rats and mice. The amount of food consumed is
      influenced by both the motivation to procure food and the consummatory act of
      ingestion. In some species, the rate of food intake remains relatively constant,
      while survival is maintained via changes in food procurement, external storage
      and internal expenditure. For example, in hamsters, metabolic signals, peripheral
      hormones and central neuropeptides influence hunger motivation, food hoarding and
      changes in energy expenditure without necessarily influencing the amount of food
      ingested. A similar suite of metabolic signals, hormones and neuropeptides is
      involved in optimizing reproductive success under fluctuating energetic
      conditions. Reproductive processes are inhibited or delayed when energy
      expenditure outstrips energy intake and mobilization from storage. Estrous
      cyclicity in Syrian hamsters is sensitive to the availability of oxidizable
      glucose, but the presence of central glucose alone is not sufficient for normal
      estrous cycles. Food deprivation-induced anestrus does not depend upon food
      deprivation-induced increases in concentrations of adrenal hormones such as
      glucocorticoids. If hormones such as insulin and leptin play a role, they might
      do so by modulating the availability of glucose detected at extra-hypothalamic
      sites, instead of or in addition to direct effects on the mechanisms that control
      gonadotropin releasing hormone secretion. Despite our ability to measure and
      manipulate gene transcription, understanding of fuel homeostasis requires
      examination of indirect effects of hormones and neuropeptides on peripheral
      metabolism, attention to the motivational as well as consummatory aspects of
      ingestion, and the study of behaviour in a natural or seminatural context.

PMID- 12193178
TI  - Role of the paraventricular nucleus microenvironment in stress integration.
AB  - The hypothalamic paraventricular nucleus is the primary controller of hypothalamo
      pituitary-adrenocortical glucocorticoid release. In performing this function, the
      paraventricular nucleus summates a variety of information from both external and
      internal sources into a net secretory signal to the adrenal cortex. In this
      review, we will provide an overview of neuronal circuit mechanisms governing
      activation and inhibition of hypophysiotrophic neurons, highlight recent
      developments in our understanding of nonsynaptic mechanisms regulating
      paraventricular cellular activity, including dendritic neuropeptide release,
      direct steroid feedback, cytokine cascades and gaseous neurotransmission, and
      illustrate the capacity for hypophysiotrophic, neurohypophysial and preautonomic
      paraventricular effector pathways to work together in control of glucocorticoid
      release. The current state of knowledge reveals the paraventricular nucleus to be
      a dynamic entity, capable of integrating diverse classes of signals into control
      of adrenocortical activation.

PMID- 12193179
TI  - Interaction between glucocorticoid hormones, stress and psychostimulant drugs.
AB  - In this review we summarize data obtained from animal studies showing that
      glucocorticoid hormones have a facilitatory role on behavioural responses to
      psychostimulant drugs such as locomotor activity, self-administration and
      relapse. These behavioural effects of glucocorticoids involve an action on the
      meso-accumbens dopamine system, one of the major systems mediating the addictive
      properties of drugs of abuse. The effects of glucocorticoids in the nucleus
      accumbens are site-specific; these hormones modify dopamine transmission in only
      the shell of this nucleus without modifying it in the core. Studies with
      corticosteroid receptor antagonists suggest that the dopaminergic effects of
      these hormones depend mostly on glucocorticoid, not on mineralocorticoid
      receptors. These data suggest that an increase in glucocorticoid hormones,
      through an action on mesolimbic dopamine neurons, could increase vulnerability to
      drug abuse. We also discuss the implications of this finding with respect to the
      physiological role of glucocorticoids. It is proposed that an increase in
      glucocorticoids, by activating the reward pathway, could counteract the aversive
      effects of stress. During chronic stress, repeated increases in glucocorticoids
      and dopamine would result in sensitization of the reward system. This sensitized
      state, which can persist after the end of the stress, would render the subject
      more responsive to drugs of abuse and consequently more vulnerable to the
      development of addiction.

PMID- 12193180
TI  - Role of NMDA receptors and MAP kinase in the amygdala in extinction of fear:
      clinical implications for exposure therapy.
AB  - Infusions into the amygdala (a brain area essential for excitatory fear
      conditioning) of either NMDA receptor antagonists or inhibitors of the NMDA
      receptor-linked mitogen activated protein kinase cascade block extinction
      learning. Conversely, the NMDA receptor agonist D-cycloserine facilitates
      extinction after either systemic administration or intra-amygdala infusion.
      Because therapeutic interventions based on extinction procedures are commonly
      used to treat fear disorders, and because D-cycloserine is a widely available and
      safe compound, D-cycloserine or similar agents might be usefully combined with
      traditional extinction-based approaches in the treatment of clinical fear.

PMID- 12193181
TI  - Variation in the vasopressin V1a receptor promoter and expression: implications
      for inter- and intraspecific variation in social behaviour.
AB  - Instability in highly repetitive microsatellite DNA located in the regulatory
      regions of genes may be a major factor producing diversity in both region
      specific gene expression and the resulting phenotypes. Polymorphisms in promoter
      regions affecting expression of genes involved in regulating behaviour may play a
      role in generating individual variation in behaviour, including psychopathologies
      in humans, and probably are also important for the evolution of behaviour. Here
      we discuss the prairie vole vasopressin V1a receptor gene as a model that may be
      useful for understanding the evolution of promoter sequences and the relationship
      between gene sequence, expression and behavioural phenotype.

PMID- 12193182
TI  - The genetic basis for psychiatric illness in man.
AB  - Following the influential genetic studies of Heston and Kety, there has been
      growing acceptance of the role of genes in determining behaviour. It is now
      recognized that most types of behaviour, from normal variations in traits such as
      personality to complex psychiatric disorders, are influenced not only by
      environmental factors but also by multiple genes. While twin and adoption studies
      have been vital in demonstrating the heritability of behaviour, the focus is now
      on the identification of the genes involved using the molecular genetic
      strategies linkage analysis and allelic association. This article will discuss
      techniques that have been used in psychiatric genetics, and how they have
      advanced our understanding of complex behaviour.

PMID- 12193183
TI  - Evaluation of Affymetrix Gene Chip sensitivity in rat hippocampal tissue using
      SAGE analysis. Serial Analysis of Gene Expression.
AB  - DNA microarrays are a powerful tool for monitoring thousands of transcript levels
      simultaneously. However, the use of DNA microarrays in studying the central
      nervous system faces several challenges. These include the detection of low
      abundance transcripts in highly complex tissue as well as estimating relatively
      low-magnitude changes in transcript levels in response to experimental
      manipulation. Many transcripts important to brain function have low expression
      levels or are expressed in relatively few cells, making them difficult to detect
      in the complex background of brain tissue. The aim of the present study is to
      evaluate the sensitivity of Gene Chip detection of transcripts in brain by using
      results from serial analysis of gene expression (SAGE) studies. The results of
      this comparison indicate that Affymetrix Gene Chips, like SAGE, only reliably
      detect medium- to high-abundance transcripts and that detection of low-abundance
      transcripts, many of which have great relevance to biological function in brain,
      is inconsistent. Specifically, we estimate that Gene Chips reliably detect no
      more than 30% of the hippocampal transcriptome when using a gross hippocampal
      dissection as the source tissue. This report provides the first broad evaluation
      of Affymetrix Gene Chip sensitivity relevant to studying the brain.

PMID- 12193184
TI  - The functional properties of the human ether-a-go-go-like (HELK2) K+ channel.
AB  - The voltage-dependent K+ channels belonging to the ether-a-go-go family (eag,
      erg, elk) are widely expressed in the mammalian CNS. Their neuronal function,
      however, is poorly understood. Among the elk clones, elk2 is the most abundantly
      expressed in the brain. We have characterized the human ELK2 channel (HELK2)
      expressed in mammalian cell lines. Moreover, we have detected helk2 mRNA and ELK2
      like currents in freshly dissociated human astrocytoma cells. HELK2 was inhibited
      by Cs+ in a voltage-dependent way (Kd was 0.7 mm, at -120 mV). It was not
      affected by Way 123398 (5 micro m), dofetilide (10 micro m), quinidine (10 micro
      m), verapamil (20 micro m), haloperidol (2 micro m), astemizole (1 micro m),
      terfenadine (1 micro m) and hydroxyzine (30 micro m), compounds known to inhibit
      the biophysically related HERG channel. The crossover of the activation and
      inactivation curves produced a steady state 'window' current with a peak around 
      20 mV and considerably broader than it usually is in voltage-dependent channels,
      including HERG. Similar features were observed in the ELK2 clone from rat, in the
      same experimental conditions. Thus, ELK2 channels are active within a wide range
      of membrane potentials, both sub- and suprathreshold. Moreover, the kinetics of
      channel deactivation and removal of inactivation was about one order of magnitude
      quicker in HELK2, compared to HERG. Overall, these properties suggest that ELK2
      channels are very effective at dampening the neuronal excitability, but less so
      at producing adaptation of action potential firing frequency. In addition, we
      suggest experimental ways to recognize HELK2 currents in vivo and raise the issue
      of the possible function of these channels in astrocytoma.

PMID- 12193185
TI  - Spatial and temporal variation of passer Per2 gene expression in two distinct
      cell groups of the suprachiasmatic hypothalamus in the house sparrow (Passer
      domesticus).
AB  - In mammals, the major pacemaker controlling circadian rhythmicity is located in
      the hypothalamic suprachiasmatic nuclei. Although there is evidence for the
      presence of a hypothalamic circadian oscillator in birds from lesioning studies,
      neuroanatomical, neurochemical and functional investigations have failed to
      identify its exact location. Two cell groups in the avian hypothalamus have been
      shown to bear characteristics of the mammalian suprachiasmatic nucleus: the
      suprachiasmatic nucleus and the lateral hypothalamic retinorecipient nucleus. We
      cloned an avian period homologue (pPer2) and investigated the temporal and
      spatial expression pattern of this gene in the house sparrow hypothalamus using
      in situ hybridization. Applying quantitative morphometry, we found rhythmic
      expression of pPer2 during light-dark as well as in constant conditions in the
      suprachiasmatic nucleus and in the lateral hypothalamus. The temporal and spatial
      distribution of pPer2 expression in the suprachiasmatic nucleus suggest a
      longitudinal compartmentalization of the nucleus with period gene expression
      being initiated in the most rostral portion of the suprachiasmatic nucleus before
      lights on. In the lateral hypothalamus, phasing of pPer2-rhythmicity appeared
      different from the suprachiasmatic nucleus. The major difference between light
      dark and constant conditions was a decrease in the amplitude of pPer2 rhythmicity
      in the suprachiasmatic nucleus. Our data demonstrate that, unlike in mammals, Per
      gene expression in the suprachiasmatic hypothalamus of the house sparrow is not
      confined to a single cell group, indicating a more complex organization of the
      circadian oscillator in the hypothalamus of birds.

PMID- 12193186
TI  - Differences in GABAergic transmission between two inputs into the perirhinal
      cortex.
AB  - We have investigated properties of GABAergic synaptic transmission in perirhinal
      cortex evoked by stimulation of temporal and entorhinal cortex sides. GABAA IPSCs
      were isolated by blockade of glutamatergic transmission in slices of adult
      perirhinal cortex; IPSC decay was best fitted with two exponentials.
      Interestingly, temporal IPSCs had a larger slow component of decay (P < 0.05)
      compared to entorhinal IPSCs. Depression of IPSCs by the GABAB receptor agonist
      baclofen was greater (P < 0.05) in the temporal input (79 +/- 4% depression) than
      the entorhinal input (65 +/- 3% depression). Furthermore, baclofen abolished the
      slow component of IPSC decay in both inputs. Activity-dependent depression of
      IPSCs at 5 Hz was greater (P < 0.05) in the temporal input [paired pulse ratio
      (PPR) 0.5 +/- 0.04] compared to that in the entorhinal input (PPR 0.67 +/- 0.02,
      n = 10). The differences in paired pulse depression between the inputs were
      removed by the GABAB receptor antagonist CGP55845A. This study demonstrates
      several differences in GABA transmission between temporal and entorhinal inputs
      including the differential activation of presynaptic GABAB receptors and
      differential regulation of inhibitory synaptic transmission. These properties may
      be important in the control of neuronal activity within perirhinal cortex.

PMID- 12193187
TI  - Dehydroepiandrosterone (DHEA) stimulates neurogenesis in the hippocampus of the
      rat, promotes survival of newly formed neurons and prevents corticosterone
      induced suppression.
AB  - Treating adult male rats with subcutaneous pellets of dehydroepiandrosterone
      (DHEA) increased the number of newly formed cells in the dentate gyrus of the
      hippocampus, and also antagonized the suppressive of corticosterone (40 mg/kg
      body weight daily for 5 days). Neither pregnenolone (40 mg/kg/day), a precursor
      of DHEA, nor androstenediol (40 mg/kg/day), a major metabolite, replicated the
      effect of DHEA (40 mg/kg/day). Corticosterone reduced the number of cells
      labelled with a marker for neurons (NeuN) following a 28-day survival period, and
      this was also prevented by DHEA. DHEA by itself increased the number of newly
      formed neurons, but only if treatment was continued throughout the period of
      survival. Subcutaneous DHEA pellets stimulated neurogenesis in a small number of
      older rats ( approximately 12 months old). These results show that DHEA, a
      steroid prominent in the blood and cerebral environment of humans, but which
      decreases markedly with age and during major depressive disorder, regulates
      neurogenesis in the hippocampus and modulates the inhibitory effect of increased
      corticoids on both the formation of new neurons and their survival.

PMID- 12193188
TI  - Group I and II metabotropic glutamate receptors modulate respiratory activity in
      the lamprey.
AB  - The respiratory role of group I and II metabotropic glutamate receptors (mGluRs)
      was investigated in the in vitro lamprey brainstem preparation by analysing
      changes in respiratory activity induced by bath application of specific agonists
      (10 and 25 micro m) and antagonists (500 micro m). Respiratory responses reached
      their maximum within 10 or 15 min, without any obvious further changes during
      application periods of 60 min The broad-spectrum mGluR agonist (1S,3R)-1
      aminocyclopentane-1,3-dicarboxylic acid (ACPD) and the specific group I mGluR
      agonist (S)-3,5-dihydroxyphenylglycine (DHPG) caused dose-dependent increases in
      respiratory frequency and peak vagal activity. DHPG at higher concentrations (50
      100 micro m) did not cause any further consistent change in respiratory
      variables. Two different agonists acting on group II mGluRs, i.e. (2S,3S,4S)
      CCG/(2S,1'S,2'S)-2-(carboxycyclopropyl)-glycine (L-CCG-I) and (2S,2'R,3'R)-2
      (2',3'-dicarboxycyclopropyl)glycine (DCG-IV), were employed. At 10 micro m DCG-IV
      increased respiratory frequency, whilst L-CCG-I did not produce any significant
      effect. Both drugs increased respiratory frequency and peak vagal amplitude at 25
      micro m. The nonselective group I and II antagonist (S)-alpha-methyl-4
      carboxyphenylglycine (MCPG) as well as the specific group I antagonist (RS)-1
      aminoindan-1,5-dicarboxylic acid (AIDA) elicited reversible reductions in
      respiratory frequency. Blockade of group II mGluRs by (2S)-alpha-ethylglutamic
      acid (EGLU) increased both frequency and peak amplitude of vagal bursts. The
      results indicate that both group I and II mGluRs have an important modulatory
      role in the control of the lamprey pattern of breathing, probably through an
      action on the rhythm generating mechanisms. They support the view that these
      receptors are activated under physiological conditions and differentially affect
      the frequency and intensity of respiratory bursts.

PMID- 12193189
TI  - Lactate in the brain of the freely moving rat: voltammetric monitoring of the
      changes related to the sleep-wake states.
AB  - Cortical lactate was monitored voltammetrically in freely moving rats equipped
      with polygraphic electrodes. Differential normal pulse voltammetric measurements
      were carried out using a lactate biosensor coated with lactate oxidase and
      cellulose acetate. Changes occurring in lactate level were in keeping with sleep
      wake states. During slow wave sleep (SWS), the lactate level decreased
      significantly (-16.2%) vs. the spontaneous waking state (W) referenced to as
      100%. During paradoxical sleep (PS), and still vs. W, it remained low (-9.0%) but
      this variation was not statistically significant. However, when this PS change
      was compared to the SWS variation, a significant increase in lactate level was
      then revealed (+8.5%). Finally, during the active waking (aW) triggered by a
      water puff stress, lactate level rose significantly in accordance with the animal
      activity (+53% compared to W). Long-term monitoring also allowed the
      determination of a circadian component in lactate production, the lowest and
      highest values being monitored during light and dark periods, respectively. The
      acrophasis of the circadian change occurred during the dark period, about 3 h
      after the light-off (+89%). It is suggested that during wakefulness astrocyte
      metabolism allows the transformation of the blood-borne glucose into lactate. The
      increase in this substrate observed during PS may fulfil the oxidative
      phosphorylation in order to supply the important ATP need of PS.

PMID- 12193190
TI  - Locomotor recovery in the chronic spinal rat: effects of long-term treatment with
      a 5-HT2 agonist.
AB  - A complete transection of the spinal cord at a low thoracic level induces a
      paraplegic syndrome that is accompanied by a loss of spinal cord serotonin
      content. Former experimental data suggest that the central pattern generator for
      locomotion, located in the lumbar segments of the spinal cord, might be able to
      generate rhythmic motor outputs (similar to automatic walking under certain
      circumstances) involving exteroceptive stimulations and activation of
      serotonergic receptors. In the present study, we investigated the effects of a
      chronic treatment using a serotonergic agonist, delivered continuously to the
      sublesionned spinal cord, and its effect on motor function recovery. The data
      obtained from behavioural, kinematic and electromyographic measurements suggest
      that the chronic stimulation of 5-HT2 type receptors allows motor function
      recovery. Behavioural measurements show a clear improvement in motor performances
      when compared to spinal animals (confirmed by kinematic observations):
      alternating steps and foot placement is recovered in these animals. However,
      electromyographic data demonstrate that the pattern of activation of the muscles
      is only restored partially.

PMID- 12193192
TI  - Cerebellar LTD facilitates but is not essential for long-term adaptation of the
      vestibulo-ocular reflex.
AB  - The induction of cerebellar long-term depression (LTD) at the parallel fibre
      Purkinje cell synapse is selectively blocked in L7-PKCi transgenic mice,
      rendering these mice unable to adaptively modify their vestibulo-ocular reflex
      (VOR) during visuo-vestibular training for a few hours. Despite this deficit,
      their eye movement performance as well as their general motor behaviour appears
      unaffected. This combination suggests that, in the long term, residual forms of
      plasticity in the vestibulo-cerebellar circuitry can compensate for the absence
      of cerebellar LTD. To investigate whether LTD-deficient mice exhibit motor
      learning in the long run, we subjected L7-PKCi transgenic mice to visuo
      vestibular training paradigms that were aimed at either increasing or decreasing
      the VOR response in the course of eight consecutive days. During the increasing
      paradigm, the VOR gain of transgenic mice increased significantly, while VOR gain
      decreased and VOR phase-lead increased during the decreasing paradigm. The impact
      of these long training periods on the VOR was significantly smaller in LTD
      deficient mice than in wild type littermates. Thus, while LTD may be necessary
      for short-term VOR adaptation, it facilitates but is not required for long-term
      adaptation of the VOR.

PMID- 12193191
TI  - Vasopressin from hypothalamic magnocellular neurons has opposite actions at the
      adenohypophysis and in the supraoptic nucleus on ACTH secretion.
AB  - Magnocellular vasopressinergic and oxytocinergic neurons of the hypothalamic
      supraoptic (SON) and paraventricular nuclei comprise the hypothalamic
      neurohypophysial system, which is crucially involved in the regulation of body
      fluid and electrolyte homeostasis. However, still controversial is to what extent
      the same system influences the secretion of adrenocorticotropic hormone (ACTH)
      from the adenohypophysis. Therefore, we selectively stimulated magnocellular
      neurons of the SON of conscious male Wistar rats via retrodialysis. As expected,
      dialysis of the SON with hypertonic medium increased both the release of
      vasopressin within the SON and the secretion of vasopressin and oxytocin into the
      systemic blood circulation. This activation of the hypothalamic-neurohypophysial
      system was accompanied by a fivefold increase in plasma ACTH concentration. This
      effect was observed only if the tip of the microdialysis probe was within the
      SON. Intravenous infusion of the vasopressin V1 receptor antagonist
      d(CH2)5Tyr(Me)AVP significantly attenuated the effects of local osmotic
      stimulation of the SON on ACTH secretion. In contrast, administration of the same
      antagonist directly into the SON significantly enhanced the osmotically
      stimulated secretion of ACTH and corticosterone, primarily by delaying the
      restoration of the hormone secretion to prestimulation levels. We conclude from
      these findings that vasopressin from the hypothalamic-neurohypophysial system
      participates in the regulation of the hormonal stress response in a
      counterbalanced manner at the level of the SON and the adenohypophysis.

PMID- 12193193
TI  - Impaired spatial and sequential learning in rats treated neonatally with D
      fenfluramine.
AB  - D-Fenfluramine, a serotonin releaser, was administered to neonatal rats on
      postnatal days 11-20 (a stage of hippocampal development analogous to third
      trimester human ontogeny). As adults, the D-fenfluramine-treated offspring
      exhibited dose-related impairments of sequential and spatial learning and
      reference memory in the absence of sensorimotor impairments. Procedures to
      minimize stress and to control for other performance effects prior to testing for
      spatial learning demonstrated that nonspecific factors did not account for the
      selective effects of D-fenfluramine on learning and memory. Developmental D
      fenfluramine-induced spatial and sequential learning deficits are similar to
      previous findings with developmental MDMA treatment. By contrast, recent findings
      with developmental D-methamphetamine treatment showed spatial learning deficits
      while sparing sequential learning. The spatial learning effects common to all
      three drugs suggest that they may share a common mechanism of action, however,
      the effects are not related to long-lasting changes in hippocampal 5-HT levels as
      no differences were found in adulthood. Whether the cognitive deficits are
      related to the effects of substituted amphetamines on corticosteroids, other
      aspects of the 5-HT system, or some unidentified neuronal substrates is not
      known, but the data demonstrate that these drugs are all capable of inducing long
      term adverse effects on learning.

PMID- 12193194
TI  - Memory impairment following status epilepticus in immature rats: time-course and
      environmental effects.
AB  - Status epilepticus (SE) has a high mortality and morbidity rate in children.
      Disturbances in learning and memory are frequently associated with SE although it
      is not clear when the cognitive deficits occur. If cognitive dysfunction occurs
      immediately following the seizure, the window of opportunity for therapeutic
      intervention is limited. The first goal of this study was to determine the timing
      of cognitive dysfunction following SE in weanling rats. As there is evidence that
      enriching the environment can improve cognitive and motor deficits following
      brain injury, our second goal was to determine whether environmental enrichment
      improves cognitive function following SE. Rats underwent lithium-pilocarpine
      induced SE at postnatal (P) day 20 and were then tested for visual-spatial memory
      in the water maze at P22, P25, P30, or P50. Rats with SE performed significantly
      worse in the water maze than control rats at all time points. Once the time
      courses of visual-spatial memory deficits were determined, a second group of P20
      rats were subjected to SE and were then placed in an enriched environment
      (enriched group) or remained in standard cages in the vivarium (nonenriched
      group) for 28 days. Following environmental manipulation, the animals were tested
      in the water maze. Rats housed in an enriched environment following the SE
      performed substantially better in the water maze than rats housed in standard
      cages. However, no differences were found between the enriched and nonenriched
      groups in EEG or histological evaluation. Although SE results in cognitive
      impairment within days of the seizure, housing in an enriched environment after
      SE has a beneficial effect on cognitive performance in rats.

PMID- 12193195
TI  - Intravenous cocaine induced-activity and behavioural sensitization in
      norepinephrine-, but not dopamine-transporter knockout mice.
AB  - Previously, it was reported that both norepinephrine transporter (NET) and
      dopamine transporter (DAT) knockout (KO) mice were sensitive to the reinforcing
      effects of cocaine. However, assessing the locomotor-stimulant effects of cocaine
      in these subjects has proven difficult due to significant differences in their
      baseline activity compared to wild-type controls. The present studies were
      designed to clarify the role of NET and DAT in the stimulant effects of acute and
      repeated cocaine utilizing these knockout mice, and thereby assess the role of
      these substrates in the locomotor stimulant effects of cocaine. Mice were
      habituated to the test environment for sufficient time to ensure equal baselines
      at the time of cocaine administration. Mice then received cocaine (3-25 mg/kg)
      intravenously according to a within-session cumulative dose-response design.
      Cocaine dosing was repeated at 48-h intervals for four sessions to assess
      behavioural sensitization. NET-KO mice exhibited a reduced response to acute
      cocaine administration compared to wild-type (WT) controls. However, comparable
      sensitization developed in NET-KO and WT mice. The DAT-KO and DAT-heterozygote
      (HT) mice displayed no locomotor activation following either acute or repeated
      cocaine administration. These data suggest a role for the NET in the acute
      response to cocaine, but no involvement in sensitization to cocaine. In contrast,
      DAT appears to be necessary for both the acute locomotor response to cocaine and
      the subsequent development of sensitization. In addition to existing data
      concerning the reinforcing effects of cocaine in DAT-KO mice, these data suggest
      a dissociation between the reinforcing and locomotor stimulant effects of
      cocaine.

PMID- 12193197
TI  - Two mechanisms of protracted reaction times mediated by dissociable cortical
      networks.
AB  - When people divide attention between two sensory modalities and respond rapidly
      to stimuli in either modality, the reaction times (RTs) are longer than when they
      selectively attend and respond to one sensory modality. There is a further
      increase in RT when subjects use different fingers to respond to stimuli from
      different modalities as compared to when they use the same finger for both
      modalities. Here we use functional magnetic resonance imaging to show that
      division of attention bilaterally activates the caudal prefrontal areas near the
      precentral sulcus and areas in the intraparietal sulcus. All RT tasks, whether
      different fingers for different modalities or one finger for both modalities was
      used, activated identical motor areas 4a, 4p, supplementary and cingulate, the
      basal ganglia and the ventral anterior thalami. The increased blood oxygen level
      dependent signal from motor cortical areas was anatomically distinct from the
      prefrontal/parietal areas. These anatomically dissociable neural substrates of
      division of attention and motor control may be responsible for the different
      types of RT delays that we have found. In the brain, there were no differences in
      the BOLD signal irrespective of whether the effector was specified a priori or
      was specified only after the sensory signal was received.

PMID- 12193196
TI  - Activation of histaminergic H3 receptors in the rat basolateral amygdala improves
      expression of fear memory and enhances acetylcholine release.
AB  - The basolateral amygdala (BLA) is involved in learning that certain environmental
      cues predict threatening events. Several studies have shown that manipulation of
      neurotransmission within the BLA affects the expression of memory after fear
      conditioning. We previously demonstrated that blockade of histaminergic H3
      receptors decreased spontaneous release of acetylcholine (ACh) from the BLA of
      freely moving rats, and impaired retention of fear memory. In the present study,
      we examined the effect of activating H3 receptors within the BLA on both ACh
      release and expression of fear memory. Using the microdialysis technique in
      freely moving rats, we found that the histaminergic H3 agonists R-alpha
      methylhistamine (RAMH) and immepip, directly administered into the BLA, augmented
      spontaneous release of ACh in a similar manner. Levels of ACh returned to
      baseline on perfusion with control medium. Rats receiving intra-BLA, bilateral
      injections of the H3 agonists at doses similar to those enhancing ACh spontaneous
      release, immediately after contextual fear conditioning, showed stronger memory
      for the context-footshock association, as demonstrated by longer freezing
      assessed at retention testing performed 72 h later. Post-training, bilateral
      injections of 15 ng oxotremorine also had a similar effect on memory retention,
      supporting the involvement of the cholinergic system. Thus, our results further
      support a physiological role for synaptically released histamine, that in
      addition to affecting cholinergic transmission in the amygdala, modulates
      consolidation of fear memories

PMID- 12193198
TI  - Neither ibotenic acid nor volkensin lesions of the nucleus accumbens shell affect
      the expression of cocaine sensitization.
AB  - Studies have shown that the nucleus accumbens shell plays an integral role in the
      expression of psychostimulant-induced behavioural sensitization. Dopaminergic
      regulation of excitatory amino acid inputs in this region of the brain could be a
      key factor in the neural influence of this phenomenon. Alterations in the
      dopaminergic innervation patterns in the shell have been demonstrated in rats
      that received repeated cocaine injections. Furthermore, lesions of brain regions
      that send projections to the shell alter psychostimulant-induced locomotion, both
      acutely and in sensitization paradigms. A previous study from our laboratory
      demonstrated that lesions of the shell before repeated cocaine treatment decrease
      the locomotor response to cocaine during the induction phase of behavioural
      sensitization. To better understand the role of this brain region during the
      expression phase of behavioural sensitization, the present study examined the
      effects of two forms of cytotoxic lesions of the shell. Rats received a
      sensitization-inducing regimen of cocaine (bi-daily injections of 15 mg/kg i.p.
      for 5 consecutive days). Two days after the last injection, rats demonstrating
      behavioural sensitization received one of three bilateral microinjections into
      the shell: (i) 0.5 micro L 0.9% saline; (ii) 2.5 micro g/0.5 micro L ibotenic
      acid (which lesions the cell bodies at the injection site); or (iii), 0.5 ng/0.2
      micro L of volkensin (a retrograde suicide transport lectin). Upon challenge with
      cocaine (15 mg/kg) 12 days after surgery, neither ibotenic acid- nor volkensin
      lesioned rats showed any difference in their locomotor response compared with
      sham controls. These data indicate that bilateral shell lesions do not affect the
      long-term expression of behavioural sensitization in cocaine-sensitized rats.

PMID- 12193199
TI  - Mice lacking the adenosine A1 receptor are anxious and aggressive, but are normal
      learners with reduced muscle strength and survival rate.
AB  - Behavioural assessment of mice lacking adenosine A1 receptors (A1Rs) showed
      reduced activity in some phases of the light-dark cycle, reduced exploratory
      behaviour in the open-field and in the hole-board, increased anxiety in the plus
      maze and dark-light box and increased aggressiveness in the resident-intruder
      test. No differences were found in spatial reference and working memory in
      several Morris water maze tasks. Both mutant mice had reduced muscle strength and
      survival rate. These results confirm the involvement of adenosine in motor
      activity, exploratory behaviour, anxiety and aggressiveness. A1Rs also appear to
      play a critical role in ageing-related deterioration.

PMID- 12193200
TI  - Two major distinct subpopulations of neurokinin-3 receptor-expressing neurons in
      the superficial dorsal horn of the rat spinal cord.
AB  - This study was designed to provide evidence for elucidating the mechanisms of
      neurokinin-3 receptor (NK3) in spinal pain modulation. First, colocalization of
      NK3 with the micro -opioid receptor (MOR1) was studied in the spinal dorsal horn
      of the rat. Confocal microscopy showed that about 44% of NK3-expressing neurons
      in laminae I and II were immunoreactive for MOR1, which corresponded to about 93%
      of the total population of MOR1-containing neurons in these laminae. Second, the
      relationship between NK3/MOR1-coexpressing neurons and those that express nitric
      oxide synthase (NOS) was examined by using a triple immunofluorescent staining
      method. About 37% of NK3-immunoreactive neurons were also NOS-immunoreactive,
      which constituted about 82% of NOS-immunoreacitve neurons in the superficial
      laminae. However, no triple-labelled neurons were detected. The present results
      indicate that there are two major distinct subpopulations of NK3-expressing
      neurons in the superficial dorsal horn, which suggests that the involvement of
      NK3 receptor in spinal nociception could be mediated by two distinct mechanisms,
      i.e. opioid and nitric oxide.

PMID- 12193205
TI  - Lymphoepithelioma-like carcinoma of the breast.
AB  - Lymphoepithelioma-like carcinoma (LELC) of the breast is a rare, newly recognized
      subtype of breast carcinoma. Distinction from medullary carcinoma is important
      because of the difference in biologic behavior of these two neoplasms and LELC of
      the breast is regarded as an unusual form of lobular carcinoma. We present the
      case of a 56-year-old female with a breast mass measuring 2 cm in diameter, which
      was diagnosed as invasive lobular carcinoma with LELC pattern. This is the ninth
      case reported in the English literature and to the best of our knowledge the
      first one with lymph node metastasis.

PMID- 12193206
TI  - Numerical evaluation of minimal biochemical test combinations for the
      identification of Enterobacteriaceae species.
AB  - Species identification of 572 clinical isolates of Enterobacteriaceae was
      determined using an in-house biochemical test panel and API 20E. The overall
      agreement was 82.7 per cent. When a numerical identification programme for
      Enterobacteriaceae was used to analyze the results of 440 E.coli isolates, the
      agreement with API 20E increased from 81.4 to 91.1 per cent. Numerical
      identification was then employed to evaluate 14 routine biochemical test panels
      used in 12 Swedish laboratories, and an additional 18 potential new test panel
      variants. The theoretical identification power of the panels was measured by a
      scoring system, based on simulated test results for the 14 most common species of
      Enterobacteriaceae. The results showed wide variations in the performance of
      different panels, with a number of panels being of insufficient quality. Among
      the 32 test panels, 6 panels indicated excellent performance. These should be
      further evaluated for routine laboratory performance. Numerical identification
      methods constitute powerful tools in the hands of the clinical microbiologist to
      aid in species identification as well as to analyze the quality of identification
      charts in use.

PMID- 12193204
TI  - Primary colorectal carcinomas and their intrapulmonary metastases: clinical,
      glyco-, immuno- and lectin histochemical, nuclear and syntactic structure
      analysis with emphasis on correlation with period of occurrence of metastases and
      survival.
AB  - BACKGROUND: The aim of the study was to correlate clinical factors (disease-free
      interval/survival) with growth pattern in terms of structural entropy of patients
      with primary colorectal carcinomas and secondary lung lesions. METHODS:
      Proliferation and apoptosis markers as well as determinants involved in
      information transfer by protein-carbohydrate interactions were monitored. The
      clinical history, surgical and histopathological reports, tumor load, survival of
      the patients with a maximum follow-up of 14 years, and sections of paraffin
      blocks of 60 colorectal carcinoma specimens and their pulmonary metastases were
      examined. Measurements of the staining intensities after processing sections of
      primary and secondary carcinomas with the marker panel and calculations of
      syntactic structure and stereological parameters were performed. RESULTS: The
      majority of primary tumors (80%, 49/60) were surgically treated at advanced tumor
      stages (pT3/pT4), with detectable lymph node involvement (34/60). Lung metastases
      were resected after a median disease-free interval of 30.5 months, an average of
      3.0 metastases adding up to a mean intrapulmonary tumor load of 9.98 ccm. The
      median survival was calculated to be 82 months after resection of the
      colon/rectal carcinomas and 40 months after that of intrapulmonary metastases. It
      was correlated with certain structural and vascular features such as vascular
      circumference. The proliferation index and several textural features were
      strongly associated with vascularization in primary and secondary tumors.
      CONCLUSIONS: Despite intra- and interindividual variations, vascularization
      properties and features such as bcl-2 positivity and CEA- and galectin-3
      associated structural entropy in primary tumors or metastases are described as
      independent prognostic features. Absence of lymph node involvement or limited
      tumor stages of colon/rectal carcinomas should not exclude patients from thorough
      postsurgical scrutiny to detect lung metastases.

PMID- 12193208
TI  - Myocarditis and sudden infant death syndrome.
AB  - This is a retrospective survey of findings of myocarditis in 437 infants under
      the age of 1 year who died suddenly and unexpectedly between 1982 and 1999, and
      were investigated at the Department of Forensic Medicine in Stockholm, Sweden.
      Myocarditis was diagnosed in 69/410 infants who died naturally (16.8%) and in
      2/27 violent deaths (7.4%). In 43/410 natural deaths (10.5%) the myocarditis was
      an isolated finding and the only explanation for cause of death and in 26 (6.3%)
      there were additional possible causes of death. The myocarditis was acute in
      45/69 and chronic in 24/69 natural deaths, and was found to occur as early as at
      a few weeks of age. No specific risk factors were found when reviewing critical
      time of year, age, gender, previous symptoms, sleeping position, aspiration of
      gastric contents and environmental factors in infant deaths with finding of
      myocarditis compared to 313 deaths due to sudden infant death syndrome.
      Myocarditis was found in 13 of 37 deaths where cultures for cytomegalovirus were
      positive. More than 50% of the foci of the isolated myocarditis were located in
      the upper part of the interventricular septum and the adjacent part of the right
      atrium, areas including parts of the conduction system. This localisation is
      significant for the cause of death when comparing deaths with myocarditis as an
      isolated finding to deaths with other possible causes.

PMID- 12193207
TI  - Activation of the p38 MAP kinase pathway is required for foam cell formation from
      macrophages exposed to oxidized LDL.
AB  - Endocytosis of oxidized low density lipoproteins (oxLDL) by macrophages, mediated
      by scavenger receptors, is thought to play a central role in foam cell formation
      and, thus, in the pathogenesis of atherosclerosis. OxLDL activates several MAP
      kinases, including the ERK, JNK and p38 MAP kinases, but the role of these
      activations in oxLDL uptake has not been studied. In the present investigation,
      we find that SB203580, a specific inhibitor of p38, blocks oxLDL-exposed J774
      cells from becoming foam cells. Inhibition of foam cell formation by blockade of
      the p38 pathway is, at least in part, due to inhibition of oxLDL-induced up
      regulation of the scavenger receptor CD36. Using pharmaceutical inhibitors and
      dominant active MAP kinase kinases, we demonstrated that activation of the p38
      pathway, but not the ERK or JNK pathways, is necessary and sufficient to
      transactivate PPARgamma, a nuclear receptor that has recently been shown to play
      a pivotal role in oxLDL-induced CD36 expression. Our results for the first time
      demonstrate a regulation of CD36 by p38, and the importance of the p38 pathway in
      regulation of foam cell formation.

PMID- 12193209
TI  - Different effects of chloroquine and hydroxychloroquine on lysosomal function in
      cultured retinal pigment epithelial cells.
AB  - Although relatively rare, retinopathy based on a disturbed metabolism of the
      retinal pigment epithelium (RPE), with ensuing degeneration of photoreceptors, is
      a known complication of treatment with the 4-aminoquinolones, chloroquine (CQ)
      and hydroxychloroquine (HCQ), in autoimmune diseases. The reported frequency of
      retinopathy, however, is much lower for HCQ than for CQ (less than 0.08% versus 1
      2%). To test whether the difference in toxicity between the two lysosomotropic
      drugs is related to different lysosomal influence, we exposed confluent RPE cell
      cultures to CQ or HCQ for 2 weeks. To induce lipofuscin (LF) formation, known to
      be accelerated by increased lysosomal pH and intra-lysosomal oxidation during
      degradation of auto-/heterophagocytosed material, such treatment was combined
      with feeding of cells with photoreceptor outer segments (POS) and hyperoxia (40%
      ambient oxygen). HCQ was found to be a less potent enhancer of lipofuscinogenesis
      compared to CQ, apparently due to its less effective inhibition of lysosomal
      degradative capacity (evaluated by vital staining of lysosomes with Lyso Tracker
      Red, and periodic acid-Schiff reaction). This conclusion is supported by the fact
      that NH4Cl, a non-fluorescent substance which acts similarly to 4
      aminoquinolones, induced an increase in LF fluorescence paralleled by increased
      periodic acid-Schiff reactivity of RPE cells.

PMID- 12193210
TI  - Suppression of antigen-specific lymphocyte proliferation by Gram-positive
      bacterial cell walls.
AB  - It is largely unknown how bacterial cell walls (BCW) modulate human immune
      responses. In the present work the effect of Gram-positive BCW on lymphocyte
      proliferation responses towards several microbial antigens (Ag) or mitogens was
      studied. Gram-positive BCW were derived from four indigenous bacterial strains
      and from one pathogen (Streptococcus pyogenes). All BCW preparations used non
      specifically suppressed the proliferation responses of peripheral blood
      mononuclear cells (PBMC) against bacterial and viral Ag, but not against
      mitogens. Both lymphocytes and macrophages or their secreted products mediated
      the suppressive effects of BCW, which were not IL-10 dependent. Furthermore, the
      expression of HLA-DR and CD86 on monocytes/macrophages was downregulated by BCW.
      Unlike in LPS-induced suppression, the CD14 pathway was not used by BCW of
      Lactobacillus casei (L.c.). The observed results indicate that Gram-positive BCW
      suppress antigen-specific lymphocyte proliferation through several mechanisms.
      This non-specific immunosuppression might be a general function of BCW in the
      bacteria-host interaction, being of importance for bacterial survival and
      pathogenicity.

PMID- 12193211
TI  - Patterns of nestin and other intermediate filament expression distinguish between
      gastrointestinal stromal tumors, leiomyomas and schwannomas.
AB  - The KIT-positive specific gastrointestinal stromal tumors (GISTs), leiomyomas,
      and schwannomas are the three most common types of primary mesenchymal tumors of
      the gastrointestinal (GI) tract. The intermediate filaments are abundant
      cytoskeletal proteins commonly used as cell differentiation markers in diagnostic
      immunohistochemistry. Their patterns have not been fully characterized in GI
      mesenchymal tumors, and could offer differential diagnostically useful
      parameters. Very recently, nestin, a class VI intermediate filament expressed in
      neuroectodermal stem cells and skeletal muscle progenitor cells, has been shown
      in GISTs and suggested as a marker for these tumors. In this study we
      immunohistochemically examined the expression of nestin and other intermediate
      filament proteins, including desmin, keratins (Ks), glial fibrillary acidic
      protein (GFAP), neurofilament, and vimentin in GISTs of different sites,
      esophageal leiomyomas and GI schwannomas. Nestin was nearly consistently present
      in GISTs of different locations whether spindle cell or epithelioid, and benign
      or malignant. It was also detected in 23 of 24 (96%) GI schwannomas, whereas
      leiomyomas were uniformly negative. Vimentin was present in both GISTs and
      schwannomas, whereas it was typically absent in leiomyomas (25% positive, usually
      focally). Desmin was present in all leiomyomas, whereas only 3% of GISTs (4 of
      140) were positive, and all schwannomas were negative. K18 was detected in a
      minority of GISTs, leiomyomas, and schwannomas. Malignant GISTs were more
      commonly keratin positive than the benign ones; there was 18% K18 positivity in
      malignant gastric and small intestinal GISTs, but 9% K18 positivity in benign
      gastric and small intestinal GISTs. Moreover, K8, albeit to a lesser degree, was
      detected in a minority of GISTs, but K7, K14, K19 and K20 were not detected. GFAP
      was present in the majority of schwannomas, whereas all GISTs were negative; some
      leiomyomas had weak cytoplasmic positivity. These results document distinctive
      patterns of intermediate filament proteins in GI mesenchymal tumors. Nestin is
      confirmed to be consistently expressed in GISTs but it is also present in most GI
      schwannomas; GFAP is helpful when separating GISTs and schwannomas, since only
      the latter are positive. The potential presence of K8 and K18 in GISTs should not
      lead to the misdiagnosis of carcinoma on biopsy.

PMID- 12193212
TI  - A case of ovarian endometrioid adenocarcinoma with yolk sac tumor component in a
      postmenopausal woman.
AB  - The co-existence of an endometrioid adenocarcinoma with an ovarian yolk sac tumor
      is very rare. Only eight cases have been reported in the English language
      literature. A 54-year-old postmenopausal woman with a 6-month history of
      progressive abdominal distension was seen at our hospital. MR imaging revealed a
      large cyst with a solid intramural node. Serum alpha-fetoprotein and CA125 levels
      were 13143 ng/ml and 170 U/ml, respectively. At laparotomy, a large tumor
      approximately 20 cm in diameter was found to occupy the abdominal cavity,
      adhering to the swollen appendix and part of the omentum. Microscopically, foci
      of endometrioid adenocarcinoma together with a yolk sac tumor component were
      observed within a large endometriotic cyst. Since the tumor was clinically staged
      1c, the patient was given 500 mg of intraperitoneal carboplatin postoperatively,
      followed by five courses of combination chemotherapy consisting of cisplatin,
      etoposide and peplomycin at 4-week intervals. The levels of both serum alpha
      fetoprotein and CA 125 decreased gradually to normal ranges and remained normal
      at the most recent follow-up on 29 December, 2001. In contrast to a very poor
      prognosis of this tumor in previously reported cases, our patient showed no sign
      of recurrence during a 21-month follow-up period.

PMID- 12193213
TI  - Lithium and KB-R7943 effects on mechanics and energetics of rat heart muscle.
AB  - The role of calcium influx on energy expenditure during cardiac contraction was
      studied. For this purpose, the described ability of lithium and KB-R 7943 (KBR)
      to diminish Ca entry through Na-Ca exchanger (Ponce-Hornos & Langer, J Mol Cell
      Cardiol 1980, 12, 1367, Satoh et al., Circulation 2000, 101, 1441) were used. In
      isolated contractions (contractions elicited after at least 5 min of rest) LiCl
      45 mmol L(-1) decreased pressure developed and pressure-time integral from 42.3
      +/- 2.7 and 14.5 +/- 1.2 to 32.1 +/- 3.4 mN mm(-2) and 8.3 +/- 0.9 mN mm(-2) s,
      respectively. A similar effect was observed in regular contractions (at 0.16 Hz
      stimulation). The presence of KBR (5 micromol L(-1)) in the perfusate induced a
      slight but not significant decrease in pressure developed and pressure-time
      integral in steady-state contractions. As it was previously described, the heat
      involved in a heart muscle contraction can be decomposed into several components
      (H1, H2, H3 and H4), but only one (H3) was associated with force generation.
      While H3 decreased with lithium in both types of contractions, H3/PtI ratio
      remained unaltered, indicating that the economy for pressure maintenance was
      unaffected. To further investigate the role of Ca entry on force development, a
      condition in which the contraction is mainly dependent on extracellular calcium
      was studied. An 'extra' stimulus applied 200 ms after the regular one in a muscle
      stimulated at 0.16 Hz induces a contraction with this characteristic (Marengo et
      al., Am J Physiol 1999, 276, H309). Lithium induced a strong decrease in pressure
      time integral and H3 associated with this contraction (43 and 45%, respectively)
      with no change in H3/PtI ratio. Lithium also reduced (53%) an energy component
      (H2) associated with Ca cycling. The use of KBR showed qualitatively similar
      results [i.e. a 33% reduction in pressure-time integral associated with the
      extrasystole (ES) with no changes in H3/PtI ratio and a 30% reduction in the H2
      component]. Li and KBR effects appear to be additive and in the presence of 45
      mmol L(-1) Li and 5 micromol L(-1) KBR the extrasystole was abolished in 77%.
      Lithium and KBR effects particularly for the extrasystole can be explained
      through the inhibition of Ca entry via Na-Ca exchange giving support to the
      participation of the Na-Ca exchanger in the Ca influx from the extracellular
      space. In addition, the results also suggest the possibility of an effect of Li
      on an additional Ca sensitive locus (different than the Na-Ca exchanger). In this
      connection, in isolated contractions lithium decreased the energy release
      fraction related to mitochondrial processes (H4) increasing the economy of the
      overall cardiac contraction.

PMID- 12193214
TI  - Effects of normobaric hyperoxia on water content in different organs in rats.
AB  - Pulmonary oxygen toxicity is a dose-dependent effect on alveolar epithelial and
      endothelial cells resulting in pulmonary oedema. Any concomitant effects on
      systemic capillary endothelium would be expected to result in capillary leakage
      and an increase in the tissues' water content. Total tissue water (TTW) in
      different organs was therefore studied in freely moving rats exposed to 100% O2
      at normobaric pressure for 24 or 48 h, and compared to air-breathing control
      rats. The TTW for the following tissues was measured: Trachea, left bronchus,
      left lung, left and right ventricle, left kidney, skin (left paw-hindlimb), skin
      (back of the rat), left brain, left eye and thigh muscle left side. There was a
      significant increase in TTW of the lung accompanied by pleural effusion after 48
      h of oxygen exposure as expected in all exposed animals. There was a small
      increase in TTW of the paw only, and a small decrease or no change in other
      tissues after 24 and 48 h of exposure. We conclude that there is no evidence of
      systemic capillary dysfunction as measured by tissue water content after exposure
      to hyperoxia in a dosage causing pulmonary oedema.

PMID- 12193215
TI  - Cardiomyocyte contractility and calcium handling partially recover after early
      deterioration during post-infarction failure in rat.
AB  - The aim of the study was to determine whether progression of heart failure is
      associated with deterioration of cardiomyocyte function. Cell dimensions,
      contractility and calcium transients were measured in cardiomyocytes isolated
      from the left ventricle of female Wistar rats 1, 4, and 13 weeks after coronary
      artery ligation or sham-operation. Relative cardiomyocyte shortening decreased
      from 26% in controls to 11% 1 week after myocardial infarction and recovered to
      18 and 20% after 4 and 13 weeks, respectively. Diastolic and systolic calcium
      concentrations increased markedly 1 week after myocardial infarction with
      subsequent reduction after 4 and 13 weeks. Time to 50% relaxation was prolonged
      by 31% after 1 week and 20% after 4 and 13 weeks with corresponding changes in
      diastolic calcium clearance. Cardiomyocyte length increased by 6, 24, and 26%
      after 1, 4 and 13 weeks, respectively, whereas myocyte width increased by 4, 11
      and 27%. Cardiomyocytes adjacent to the infarct hypertrophied more and initially
      had more markedly impaired function than in the remote area. Left ventricular
      diastolic diameter assessed by echocardiography increased by 47, 66 and 84% after
      1, 4 and 13 weeks, respectively, and systolic diameter increased by 120, 162 and
      194%. Left ventricular end-diastolic pressure increased from 6 mmHg to 24, 25 and
      36 mmHg. Whereas initial deterioration of cardiac function is associated with
      reduced cardiomyocyte contractile function, chronic heart failure progression is
      not accompanied by further impairment of intrinsic cardiomyocyte contractility in
      this model. Cardiomyocyte hypertrophy and dysfunction are more marked adjacent to
      the infarction.

PMID- 12193216
TI  - Localization of a protein inhibitor of carbonic anhydrase in pig tissues.
AB  - The protein inhibitor of carbonic anhydrase (CA), pICA, was localized in pig
      tissues by an immunohistochemical technique, using rabbit antipICA IgG. Staining
      for pICA was found in liver sinusoids and kidney glomeruli, where phagocytic
      cells are located, i.e. Kupffer and mesangial cells, respectively. pICA was not
      found inside parenchymal cells, or in tissues from striated muscle, heart, eye or
      lung. It is concluded that the function of pICA is perhaps to bind the carbonic
      anhydrase isozymes CA I, II, and III, released from erythrocytes into the blood
      circulation by intravascular haemolysis. The complex of CA-pICA in plasma may
      then be transported to the reticuloendothelial system, for degradation and
      reclamation of CA-bound zinc. This would be similar to the fate of the
      haemoglobin-haptoglobin complex for the recycling of iron.

PMID- 12193217
TI  - Regulation of Ca2+ channel and phosphatase activities by polyamines in intestinal
      and vascular smooth muscle--implications for cellular growth and contractility.
AB  - Polyamines added extracellularly to intestinal and vascular smooth muscle cells
      cause relaxation through inhibition of Ca2+ channel activity. Intracellularly
      applied polyamines also affect Ca2+ channel properties. Polyamines do not readily
      pass over the plasma membrane because of their positive charges but in
      permeabilized smooth muscle preparations they have free access to the cytoplasm.
      In this system they increase sensitivity of the contractile machinery to Ca2+
      through inhibition of myosin phosphatase activity. The magnitude of Ca2+ channel
      and phosphatase inhibition depends on the number of positive charges on the
      polyamine molecule. Polyamines have an obligatory, but yet undefined, role in
      regulation of cell growth and proliferation. Several groups of protein kinases,
      such as tyrosine and mitogen activated protein (MAP)-kinases transmit the growth
      signal from the plasma membrane to the cell nucleus where mitosis and protein
      synthesis are initiated. The data reviewed here show that polyamines may affect
      such signal transmission via inhibition of phosphatase activity.

PMID- 12193218
TI  - Adaptive stress response of glutathione and uric acid metabolism in man following
      controlled exercise and diet.
AB  - Ergometer cycling performance as well as acute exercise-induced changes in the
      metabolism of energy-intermediates and glutathione (GSH) were investigated in
      skeletal muscle (SM) of 15 healthy young male subjects (VO(2max) approximately
      54.7 mL kg(-1) min(-1), age approximately 25 years), before and after 3 days of
      controlled 'ioverload-training' in combination with either high (62% of energy
      intake) or low (26% of energy intake) dietary intake of carbohydrates. The intake
      of a carbohydrate-rich diet clearly reduced the depletion of SM glycogen
      following the short-term training period, paralleled with a positive effect on
      the endurance performance, but not on high-intensity work-performance. An
      'delayed over-reaching effect', defined as impaired work-performance, was
      observed after 2.5 days of recovery from the short-term training period,
      irrespective of the carbohydrate content of the diet and basal glycogen level in
      SM. Taken together, the main and novel findings of present investigation are: (1)
      an acute decrease of reduced GSH content and altered thiol-redox homeostasis in
      SM induced by strenuous high-intensity exercise; (2) an adaptive elevation of
      basal GSH level following the short-term training period; (3) an adaptive
      decrease of basal GSH level following 2.5 days recovery from training; (4)
      evidence of a relationship between the SM fibre type, physical performance
      capacity and GSH turnover during acute bouts of exercise; and (5) no evident
      effect of the level of carbohydrate intake on metabolism of GSH or energy
      intermediates. Furthermore, the induction of acute oxidative stress in exercising
      human SM and the adaptive responses to training are suggested to provide a
      protective antioxidant phenotype to the exercising SM during periods with
      repeated intense intermittent training.

PMID- 12193220
TI  - Evidence that brain glucose availability influences exercise-enhanced
      extracellular 5-HT level in hippocampus: a microdialysis study in exercising
      rats.
AB  - The relationship between brain glucose and serotonin is still unclear and no
      direct evidence of an action of brain glucose on serotonergic metabolism in
      central fatigue phenomena has been shown yet. In order to determine whether or
      not brain glucose could influence the brain 5-hydroxytryptamine (5-HT) system, we
      have monitored in microdialysis the effects of a direct injection of glucose in
      rat brain hippocampus on serotonergic metabolism [i.e. 5-HT, 5
      hydroxyindoleacetic acid (5-HIAA) and tryptophan (TRP)], during high intensive
      treadmill running. The injection was performed just before and after exercise. We
      have shown that glucose induced a decrease of brain 5-HT levels to a minimum of
      73.0 +/- 3.5% of baseline after the first injection (P < 0.01) and to 68.5 +/-
      5.5% of baseline after the second injection (P < 0.01) and consequently prevented
      the exercise-induced 5-HT enhanced levels. We have observed the same phenomenon
      concerning the 5-HIAA, but brain TRP levels were not decreased by the injections.
      In conclusion, this study demonstrates that brain glucose can act on serotonergic
      metabolism and thus can prevent exercise-induced increase of 5-HT levels. The
      results also suggest that extracellular brain glucose does not act on the
      synthesis way of 5-HT, but probably on the release/reuptake system.

PMID- 12193219
TI  - Evidence that action potential generation is not the exclusive determinant to
      trigger spontaneous myogenic contraction of guinea-pig urinary bladder smooth
      muscle.
AB  - Urinary bladder smooth muscle (UBSM) exhibits spontaneous contraction. This
      spontaneous mechanical activity is myogenic and can be closely related to the
      UBSM cell action potential to facilitate Ca2+ influx through voltage-gated Ca2+
      channels. In the present study, to know whether this membrane electrical event is
      the exclusive mechanism to trigger spontaneous smooth muscle contraction, we
      compared the inhibitory effects of Ca2+ channel blockers on the spontaneous
      action potential and mechanical activity in the isolated guinea-pig UBSM. Both
      action potential and rhythmic contraction were generated spontaneously in the
      presence of atropine (1 microM), phentolamine (1 microM), propranolol (1 microM),
      suramin (10 microM) and tetrodotoxin (1 microM), which suggest that both
      phenomena were myogenic in origin. Nisoldipine (100 nM) and diltiazem (10 microM)
      completely eliminated the generation of action potential whereas its frequency
      was dramatically increased by a dihydropyridine Ca2+ agonist, BayK 8644 (1
      microM). In contrast to disappearance of action potential in the presence of Ca2+
      channel blockers, spontaneous contraction of UBSM was inhibited only partly by
      nisoldipine or diltiazem and most of the mechanical components persisted in these
      channel blockers. These results indicate that spontaneous action potential in
      UBSM cell is generated through the activation of L-type voltage-gated Ca2+
      channels. The subsequent elevation of intracellular Ca2+ concentrations during a
      burst of action potentials can be partly responsible for the induction of UBSM
      mechanical activity. In addition, the present study provides evidence that UBSM
      spontaneous mechanical activity is also attributable to the mechanism(s) other
      than the generation of Ca2+ spike.

PMID- 12193221
TI  - Responses of the bronchial and pulmonary circulations to short-term nitric oxide
      inhalation before and after endotoxaemia in the pig.
AB  - The physiological responses of the bronchial circulation to acute lung injury and
      endotoxin shock are largely unexplored territory. This study was carried out to
      study the responsiveness of the bronchial circulation to nitric oxide (NO)
      inhalation before and after endotoxaemia, in comparison with the pulmonary
      circulation, as well as to study changes in bronchial blood flow during
      endotoxaemia. Six anaesthetized pigs (pre-treated with the cortisol-synthesis
      inhibitor metyrapone) received an infusion of 10 microg/kg endotoxin during 2 h.
      Absolute bronchial blood flow was measured via an ultrasonic flow probe around
      the bronchial artery. The pigs received increasing doses of inhaled NO over 5 min
      each (0, 0.2, 2 and 20 ppm) before and after 4 h of endotoxaemia. The increase in
      bronchial vascular conductance during 5 min of inhalation of 20 ppm NO before
      endotoxin shock was significantly higher (area under curve (AUC) 474.2 +/- 84.5%
      change) than after endotoxin shock (AUC 118.2 +/- 40.4%, P < 0.05 Mann-Whitney U
      test). The reduction of the pulmonary arterial pressure by 20 ppm NO was not
      different. A short rebound effect of the pulmonary arterial pressure occurred
      after discontinuation of inhaled NO before endotoxaemia (AUC values above
      baseline 54.4 +/- 19.7% change), and was virtually abolished after endotoxaemia
      (AUC 6.1 +/- 4.0%, P = 0.052, Mann-Whitney U-test). Our results indicate that the
      responsiveness of the bronchial circulation to inhalation of increasing doses of
      inhaled NO during endotoxin shock clearly differ from the responsiveness of the
      pulmonary circulation. The reduced responsiveness of the bronchial circulation is
      probably related to decreased driving pressure for the bronchial blood flow. The
      absence of the short rebound effect on pulmonary arterial pressure (PAP) after
      induction of shock could be related to maximum constriction of the pulmonary
      vessels at 4 h.

PMID- 12193222
TI  - Cross-priming is under control of the relB gene.
AB  - Cross-priming is an important mechanism of intercell transfer of antigenic
      material leading to the specific activation of cytotoxic T lymphocytes. Dendritic
      cells (DCs) are considered the central antigen-presenting cell in cross-priming.
      Here we decided to probe the role of the relB gene, a regulator of DC
      differentiation, in the in vivo cross-priming of a model tumour antigen, TAP(-/-)
      murine embryo cells (MEC), expressing human adenovirus type 5 early region 1. To
      this end, we used relB(-/-) mutant mice to generate bone marrow (BM) chimeras as
      these possess few residual DC but are capable of initiating CD4+ and CD8+ T-cell
      responses in vivo. Our results show that relB(-/-) BM chimeras are unable to
      cross-prime CD8+ T cells, suggesting that the relB gene regulates cross-priming.

PMID- 12193223
TI  - Beyond self and nonself: fuzzy recognition of the immune system.
AB  - Self-nonself discrimination of the immune system is a widely accepted principle
      of immunology; however, abundant existing and physiologic functions of harmless
      autoimmunity as well as degeneracy of antigen recognition expose the over
      simplification of the two-valued doctrine. Here, based on infinite-value fuzzy
      logic, we propose that the immune repertoire, as a consequence of central
      tolerance, is able to recognize both self and nonself antigens to a certain
      degree, compensating for the inadequacy of the two-valued self-nonself doctrine.
      Subthreshold recognition of self antigens is necessary for the generation of
      regulatory T cells, survival of both naive and memory T cells and other
      physiologic functions. The kind and magnitude of the immune response depend on
      the affinity between the antigen (self and foreign) and the T-cell receptor, and
      microenvironmental and cellular threshold. The outcome of self-nonself
      discrimination is influenced fundamentally by central tolerance and further
      dynamic regulation of threshold molecules both in time and space. Understanding
      the fuzzy feature of the immune system may shed light on mechanisms of autoimmune
      diseases, cancers and other chronic diseases, and lead to the design of novel
      vaccines or immunotherapies.

PMID- 12193224
TI  - Extensive and preferential Fas/Fas ligand-dependent death of gammadelta T cells
      following infection with Listeria monocytogenes.
AB  - In the spleens of mice infected intraperitoneally with the bacterium Listeria
      monocytogenes, both alphabeta and gammadelta T cells became rapidly activated,
      followed by a massive apoptotic death response predominantly within the
      gammadelta population. The death response involved two major splenic gammadelta T
      cell subsets and was Fas/Fas ligand (Fas-L)-dependent. Among T cells isolated
      from the Listeria-infected spleen, Fas-L was almost exclusively expressed in
      gammadelta T cells. gammadelta T cells coexpressed Fas and Fas-L, suggesting
      activation-induced suicide as a mechanism of their death. In vivo treatment with
      an antibody specific for CD3epsilon induced activation, preferential Fas-L
      expression and apoptosis of gammadelta T cells, resembling the response pattern
      in listeriosis, whereas antibodies specific for T-cell receptor-beta (TCR-beta)
      or TCR-delta did not, suggesting that the complete response seen in listeriosis
      requires both gammadelta TCR engagement and additional stimuli. L. monocytogenes
      causes early nonspecific, Fas-independent lymphocyte death in heavily infected
      tissues. In contrast, the death response described here is selective, Fas
      dependent and triggered at low local levels of bacteria, suggesting that it is
      controlled by interactions with other infection-activated host cells, and perhaps
      part of a regulatory circuit specifically curtailing gammadelta T cells.

PMID- 12193225
TI  - Identification of rat quantitative trait loci that regulate LPS-induced pro
      inflammatory cytokine responses.
AB  - Bacterial lipopolysaccharides (LPSs) trigger innate immune effector functions,
      such as the production of pro-inflammatory cytokines. Here we utilized major
      histocompatibility complex (MHC)-congenic rats to dissect the genetic basis of
      strain-dependent variations of LPS-induced tumour necrosis factor-alpha (TNF
      alpha) levels in a whole blood in vitro assay. PVG.1AV1 background was associated
      with a high response, ACI background with a medium response, and LEW.1AV1 and DA
      backgrounds were associated with low responses. To determine the location of
      regulating non-MHC genes, a genome-wide linkage analysis with 236 microsatellite
      markers was performed on 186 F2 progeny of high TNF-alpha responder PVG.1AV1 and
      MHC identical but low TNF-alpha responder LEW.1AV1 rats. A region on rat
      chromosome 1 displayed linkage to LPS-induced TNF-alpha responses (P = 3.3 x 10
      5). In addition, a locus on chromosome 2 was linked to responses of both
      interleukin-6 (IL-6) (P = 2.3 x 10-5) and TNF-alpha (possible linkage, P = 8 x 10
      3). Both chromosome regions have been linked to inflammatory diseases in rats,
      and so have the homologous regions in mice and humans. We therefore suggest that
      continued genetic dissection of the described in vitro phenotypes will give clues
      to both normal physiological regulation of LPS-induced TNF-alpha production and
      disease pathways.

PMID- 12193226
TI  - Dendritic cells present an intracellular viral antigen derived from apoptotic
      cells and induce a T-cell response.
AB  - We investigated if dendritic cells (DCs) were able to present intracellularly
      located antigens derived from apoptotic cells to T cells, thereby inducing a CD4+
      and a CD8+ response. A transfected cell line with the cytomegalovirus-derived
      protein pp65 was triggered to go into apoptosis by ultraviolet B (UVB)
      irradiation, and after the uptake of apoptotic cells by DC, the activation and
      proliferation of T cells were determined. We found that DC efficiently
      phagocytosed apoptotic cells and induced a CD4+ and a CD8+ T-cell response
      specific for the viral protein pp65. This mechanism can be useful for vaccination
      studies to induce an antiviral immune response.

PMID- 12193227
TI  - Endomorphins 1 and 2 inhibit IL-10 and IL-12 production and innate immune
      functions, and potentiate NF-kappaB DNA binding in THP-1 differentiated to
      macrophage-like cells.
AB  - We evaluated immunological effects of opioid peptides endomorphins 1 and 2 on the
      production of interleukin-10 (IL-10) and IL-12 cytokines, functions related to
      innate immunity and NF-kappaB DNA binding in human cell line THP-1. Endomorphins
      1 and 2 inhibited lipopolysaccharide (LPS)-stimulated IL-10 and IL-12 production
      in THP-1 differentiated to macrophage-like cells by phorbol 12-myristate 13
      acetate (PMA). Similarly, they suppressed LPS-stimulated IL-10 and IL-12
      production in THP-1 matured to monocytes by 1alpha,25-dihydroxyvitamin D3. In
      addition, endomorphins 1 and 2 led to marked potentiation of NF-kappaB binding in
      THP-1 differentiated to macrophage-like cells. Furthermore, these endomorphins
      further potentiated LPS-induced NF-kappaB binding. Moreover, they inhibited
      chemotaxis, phagocytosis of Escherichia coli and PMA-stimulated production of
      hydrogen peroxide in THP-1 differentiated to macrophage-like cells. These results
      suggest that endomorphins 1 and 2 may inhibit THP-1 functions, such as cytokine
      production and functions related to innate immune, and potentiate NF-kappaB DNA
      binding in THP-1.

PMID- 12193228
TI  - Sema7A is a potent monocyte stimulator.
AB  - Sema7A is a recently described member of the semaphorin family that is associated
      with the cell surface via a glycophosphatidylinositol linkage. This study
      examined the mRNA expression and biological properties of this protein. Although
      the expression of Sema7A was demonstrated in lymphoid and myeloid cells, no
      stimulation of cytokine production or proliferation was evident in B or T cells.
      In contrast, Sema7A is an extremely potent monocyte activator, stimulating
      chemotaxis at 0.1 pm and inflammatory cytokine production (interleukin-1 (IL
      1beta), tumour necrosis factor-alpha (TNF-alpha), IL-6 and IL-8) and superoxide
      release at 1-10 pm. Sema7A is less effective at stimulating neutrophils. Sema7A
      also significantly increases granulocyte-macrophage colony-stimulating factor (GM
      CSF) production from monocytes but has no consistent effect on IL-10, IL-12 or IL
      18. Sema7A can also induce monocytes toward a dendritic cell morphology. Sema7A
      is expressed in monocytes and probably released through proteolysis and acts as a
      very potent autocrine activator of these cells.

PMID- 12193229
TI  - Characterization, expression and functional aspects of a novel protein tyrosine
      phosphatase epsilon isoform.
AB  - This report describes the identification and characterization of a novel
      cytoplasmic isoform of human protein tyrosine phosphatase epsilon (PTPepsilon).
      The novel isoform, denoted cyt-PTPepsilonPD1, displays only the N-terminal
      catalytic, active phosphatase domain 1 (PD1) which is common in all known
      PTPepsilon isoforms. In addition, it contains a unique 132-residue long C
      terminal end with no known motifs or homology to other characterized proteins.
      RNAse protection assay on isolated leucocyte subpopulations and selected cell
      lines demonstrated highest expression of cyt-PTPepsilonPD1 in monocytes. The mRNA
      encoding cyt-PTPepsilonPD1 is detected as distinct transcript(s) by Northern blot
      analysis and is a result of alternative splicing. cyt-PTPepsilonPD1 shows similar
      cellular localization in transfected cells, both in the cytoplasm and nucleus, as
      has been previously described for cytoplasmic PTPepsilon isoform. Our previous
      data suggest that the expression of cytoplasmic PTPepsilon inhibits the mitogen
      activated protein kinase cascade through the extracellular signal-regulated
      kinase 1 and 2 pathway. A similar functional role is also presented here for cyt
      PTPepsilonPD1, supporting our previous data suggesting that the catalytic first
      PD of PTPepsilon is responsible for this inhibition.

PMID- 12193230
TI  - Differential expression of cytokines (IL-2, IFN-gamma, IL-10) and adhesion
      molecules (VCAM-1, LFA-1, CD44) between spleen and lymph nodes associates with
      remission in chronic relapsing experimental autoimmune encephalomyelitis.
AB  - We have recently established chronic relapsing experimental autoimmune
      encephalomyelitis (CR-EAE) in SJL mice with a modified protocol. In this model,
      splenectomy aborts the relapsing-remitting course of the disease, and adoptive
      transfer of lymphocytes of the local draining lymph nodes (LNs) to naive
      recipients exacerbates the disease. Adoptive transfer of splenic cells converted
      acute EAE into CR-EAE in the naive recipients. In light of the different roles of
      the spleen and LNs in the evolution of CR-EAE, we examined by semiquantitative
      reverse-transcription polymerase chain reaction (RT-PCR) whether a differential
      mRNA expression profile of cytokines and cellular adhesion molecules (CAMs) in
      spleen versus LN was associated with relapse or remission in CR-EAE. All the
      cytokines tested (interleukin-1beta (IL-1beta), IL-2, IL-4, IL-7, IL-10,
      interferon-gamma (IFN-gamma)) as well as CAMs (ICAM-1, ICAM-2, VCAM-1, LFA-1 and
      CD44) were expressed at substantial levels in both spleen and LNs. Interestingly,
      disease remission was found to be associated with an increased mRNA expression of
      IL-2 and IFN-gamma in LNs and a decreased IL-10 mRNA level in the spleen. On the
      other hand, an increased mRNA expression of VCAM-1, LFA-1 and CD44 was observed
      in the spleens in comparison with that in LNs of mice, with remission. During
      relapses, mRNA expression of the tested molecules did not significantly differ
      between spleens and LNs. Our results suggest that a differential and polarized
      expression profile of certain cytokines and CAMs in spleen versus LN could
      provide molecular correlates of the cyclic pathogenesis of CR-EAE.

PMID- 12193231
TI  - Differences in LPS-induced activation of bronchial epithelial cells (BEAS-2B) and
      type II-like pneumocytes (A-549).
AB  - Lipopolysaccharide (LPS) as a major component of the outer membrane of gram
      negative bacteria stimulates various cells to initiate a signalling cascade which
      ultimately leads to cell activation and expression of immunoregulatory or
      inflammatory cytokines. The human respiratory epithelium is an important
      environmental interface, but differences in LPS-induced cell activation between
      bronchial and alveolar epithelial cells have not yet been investigated in detail.
      First, the expression of Toll-like receptors (TLRs), as pattern-recognition
      receptors, was investigated for the bronchial epithelial cells and type II-like
      pneumocytes, demonstrating that they fulfil the prerequisites for LPS signalling.
      Thereafter, the effects of LPS, soluble CD14 (sCD14) and LPS-binding protein
      (LBP) on the release of interleukin-6 (IL-6) and IL-8 were studied. In the
      presence of LPS, sCD14 induced a significant and concentration-dependent cytokine
      release in type II-like pneumocytes, whereas the response of bronchial epithelial
      cells to sCD14 stimulation was low, implicating sCD14-independent activation
      mechanisms. Furthermore, LBP revealed inhibitory effects on the activation of
      alveolar epithelial cells, which may represent a novel local defence mechanism
      during gram-negative infection. We conclude that distinct pathways exist for LPS
      induced activation of bronchial and alveolar epithelial cells.

PMID- 12193232
TI  - Apoptosis of the teratocarcinoma cell line Tera-1 leads to the cleavage of HERV
      K10gag proteins by caspases and/or granzyme B.
AB  - Redistribution, post-translational modifications and coclustering with viral
      antigens contribute to the immunogenicity of apoptotic cell-derived autoantigens.
      Almost all known targets of the humoral autoimmune response in systemic lupus
      erythematosus (SLE) are cleaved by caspases or granzyme B during apoptosis.
      Antibodies against retroviral proteins can frequently be detected in the sera of
      SLE patients without overt retroviral infections. These antibodies may represent
      cross-reactive antibodies or may have been induced by proteins encoded by
      endogenous retroviral sequences. We used Tera-1 cells that abundantly express a
      group-specific antigen of human endogenous retroviruses, HERV-K10gag polyprotein,
      to investigate its processing during apoptosis. Tera-1 cells induced to undergo
      apoptosis showed an altered HERV-K10gag processing compared with viable cells. In
      addition, granzyme B was able to cleave HERV-K10gag isolated from viable Tera-1
      cells. Similar to nuclear autoantigens, endogenous retroviral proteins are
      cleaved during the execution phase of apoptosis. These post-translational
      modifications may result in the generation of T-cell neoepitopes or a changed
      epitope hierarchy of retroviral proteins. Therefore, immunogenicity of retroviral
      antigens in SLE patients may result from a similar mechanism as described for
      nuclear autoantigens.

PMID- 12193233
TI  - Activated T cells in the surface secretion on the adenoid--a flow cytometric
      study.
AB  - We previously demonstrated the presence of leucocytes in the adenoid surface
      secretion with the ability of immunoglobulin A (IgA), IgM and IgG production as
      well as production of cells with phagocytic capacity. In the present study, we
      investigated the presence of activated T cells in the secretion. Adenoid surface
      secretion from 12 children subjected to adenoidectomy was obtained with an
      imprint method. From six children, peripheral blood was also obtained. By flow
      cytometry, the number of lymphocytes, granulocytes, epithelial cells and red
      blood cells was analysed as well as the expression on lymphocyte subsets of the
      following antigens: CD3, CD4, CD8, CD19, CD25, CD38, CD45RO, CD45RA, HLA-DR,
      TcRgd, CD161 and l-selectin. The majority of T cells were activated and to a
      significantly higher degree were CD45RO+, CD161+ and l-selectin-, as compared
      with the corresponding peripheral blood. The median percentage of B cells and T
      cells in the secretion were 81 and 13%, respectively. In conclusion, the
      proportion of B and T cells in the adenoid surface secretion is significantly
      different as compared with the peripheral blood. The T cells in the adenoid
      surface secretion are to a high degree activated. The results suggest that the
      leucocytes in the surface secretion are part of the mucosal defence.

PMID- 12193234
TI  - The study of T-cell activation in peripheral blood and spleen of hepatosplenic
      patients suggests an exchange of cells between these two compartments in advanced
      human Schistosomiasis mansoni infection.
AB  - A histopathological and immunophenotypic study was performed on the spleen of
      patients with hepatosplenic (HS) schistosomiasis mansoni. Morphological data
      demonstrated that all HS patients presented features related to Schistosoma
      mansoni-induced splenomegaly, such as red pulp congestion and atrophy/hyperplasia
      of white pulp. The morphological diversity of the white pulp seems to be
      associated with the expansion of activated CD4+ T-cell subpopulation. The data
      obtained suggest that the spleen is an important site for T-cell activation
      during severe chronic infection with S. mansoni. In addition, we have compared
      the cell populations/subpopulations presented in the peripheral blood with that
      observed in the spleen of patients with HS schistosomiasis mansoni. We observed a
      significant increase in the percentage of activated CD4+HLA-DR+ and CD8+HLA-DR+ T
      cells in both the spleen and the peripheral blood of HS patients in comparison
      with noninfected individuals (NOR). These data suggest an exchange of cells
      between these two compartments. However, we observed normal expression of the
      CD28 molecule by CD8+ T cells in the spleen, despite a lower percentage of these
      cells in the peripheral blood. This finding supports the hypothesis that the
      decrease in CD28 expression, by CD8+ cells, is an event that takes place outside
      the spleen during human schistosomiasis infection. The most important conclusion
      is the fact that the analysis of T-cell activation in the peripheral blood
      reflects the major immunological reactivity that occurs in the spleen during
      human schistosomiasis and that the morphological aspects of the spleen may
      reflect the functional activity of T cells. The specificities of T cells and the
      roles they may play in the pathogenesis during chronic schistosomiasis now need
      to be determined.

PMID- 12193235
TI  - The evolution and breakdown of the immune system: implications for development of
      autoimmune diseases.
AB  - At the most recent meeting of the Scandinavian Society for Immunology in Bergen,
      one of the major target phenomena was autoimmune diseases. The approach started
      from the evolutionary origins of immunity, went on to review some of the notable
      advances in molecular architecture of immune processes and finally focussed the
      findings on autoimmune disease.

PMID- 12193236
TI  - Mental health issues of peacekeeping workers.
AB  - The end of the Cold War has brought a dramatic change to the international
      political situation and the role of the United Nations peacekeeping operations
      (PKO) has drawn increased attention. While many reports on PKO have focused on
      political or sociologic considerations, the mental health of the peacekeepers
      themselves has received little attention and psychiatric problems that can have a
      negative impact on mission success have been largely ignored. Participation in
      PKO creates a number of stressors and serious psychiatric and/or physical
      disorders may result. Yet, there is little research on this topic, either
      domestically or globally, and the methodology for clinical intervention remains
      in an early stage of development. We have reviewed previous reports to determine
      how various stressors before, during and after deployment affect the
      participants. Research in associated fields (e.g. crisis workers and military
      personnel) are also reviewed and their application to peacekeeping psychiatry is
      discussed. It must be admitted that the significance of PKO is arguable and each
      PKO is unique in terms of the nature of its mission and the local situation. Yet,
      the relationship between the psychiatric status of the personnel and the
      characteristics of an individual mission has never been studied. At present, no
      clear consensus regarding a framework for psychiatric intervention exists.
      Studies that enhance the recognition and significance of peacekeeping psychiatry
      are likely to improve the efficacy of PKO.

PMID- 12193237
TI  - Parent-infant relationship global assessment scale: a study of its predictive
      validity.
AB  - The Parent-Infant Relationship Global Assessment Scale (PIRGAS; Zero to Three,
      1994) provides a continuously distributed scale of infant-parent relationship
      adaptation, raging from 'well-adapted' to 'dangerously impaired'. The present
      study examines the predictive validity of the PIRGAS in a high-risk sample by
      coding relationship adaptation level from a single sample of 10 min of
      unstructured free play between mothers and their 20-month-old infants and
      examining its relationship to subsequent interaction with mothers and behavior
      problems at 24 months. Relationship adaptation assessed reliably from
      observations of only 10 min of free play between mothers and their infants at 20
      months of age using PIRGAS predicted subsequent mother- infant interaction in a
      laboratory based problem-solving paradigm (Crowell procedure) at 24 months and
      internalizing symptomatology of Child Behavior Checklist at age 24 months. These
      results contribute to the predictive validity of the PIRGAS as a measure of
      mother-infant relationship adaptation.

PMID- 12193239
TI  - Relationships between serum magnesium levels and clinical background factors in
      patients with mood disorders.
AB  - We measured serum magnesium (Mg) levels in 71 in-patients and out-patients with
      mood disorders and in 30 healthy controls and investigated the relationships
      between serum Mg levels and clinical background factors. Serum Mg levels were
      found to be significantly higher in patients with mood disorders than in
      controls. Serum Mg levels showed no significant correlation with patient sex,
      age, diagnosed subtype and disease phase in the mood disorder group. Serum Mg
      levels in patients with major depressive disorder who were taking psychotropic
      drugs were not significantly different from levels seen in patients with major
      depressive disorder who were not taking psychotropic drugs. These results suggest
      that the high serum Mg levels noted in patients with mood disorder are related to
      the underlying disorder itself and are not influenced by clinical background
      factors.

PMID- 12193240
TI  - A behavior therapy program combined with liquid nutrition designed for anorexia
      nervosa.
AB  - We have introduced behavior therapy as standard in-patient treatment for anorexia
      nervosa and have modified the treatment program. At first, we used Fukamachi's
      activity restriction therapy (FT), followed by Token economy therapy (TET), which
      combined token economy with FT. Finally, we have developed Kyoto Prefectural
      University of Medicine Behavior Therapy (KPT). According to KPT, only liquid
      formula is given in the early stages of hospitalization and a target weight is
      not set at admission. We examined the effect of these three programs with respect
      to bodyweight gain. Thirty-five anorexic patients participated in these three
      programs in our hospital: seven completed FT, seven completed TET and 21
      completed KPT. We compared the effects of these three programs on body mass index
      (BMI). Furthermore, the effects of these three programs on BMI were compared at
      admission, 1 month after admission and at discharge, 6 months after discharge. In
      addition, the rate of increase of BMI for the following three periods was
      investigated: 1 month after admission, total hospitalization (from admission to
      discharge) and from admission to 6 months after discharge. The result is that KPT
      was the most effective of the three programs with regard to both the amount and
      the rate of increase of BMI at all points and there is a significant difference
      between KPT and FT. This effectiveness may be attributable to the use of an oral
      liquid formula, the setting of target weight at a later stage of hospitalization
      and the release of activity restriction based on weight gain.

PMID- 12193238
TI  - Proton magnetic resonance spectroscopy of the inferior frontal gyrus and thalamus
      and its relationship to verbal learning task performance in patients with
      schizophrenia: a preliminary report.
AB  - Previous research has found frontal lobe involvement in memory impairment in
      schizophrenia. In the present study, proton magnetic resonance spectroscopy was
      performed in 13 young patients with schizophrenia and 13 normal control subjects.
      Spectra were obtained from a voxel of 2 x 2 x 1.5 cm(3) in the bilateral inferior
      frontal gyrus and thalamus. Subjects were given a verbal learning task and
      stimulus category repetition (SCR) was calculated from the performance of the
      task. Significantly reduced N-acetylaspartate (NAA)/choline-containing compounds
      ratios were found in the left inferior frontal cortex of patients compared with
      controls. The total number of words recalled by patients was significantly lower
      than that recalled by controls. In all subjects, SCR scores were positively
      correlated with NAA/phosphocreatine ratios of the left inferior frontal cortex,
      which showed a trend towards a decrease in patients. These results support the
      notion of metabolic abnormalities in the left inferior frontal region related to
      verbal memory deficits in patients with schizophrenia.

PMID- 12193242
TI  - Japanese version of the Quality of Relationship Inventory: its reliability and
      validity among women with recurrent spontaneous abortion.
AB  - Until now most of the research on social support has concentrated on general
      support in relationship to the whole group of people around each individual. In
      contrast, only a few studies have dealt with individual-specific support (i.e.
      social support from a particular individual relationship). The Quality of
      Relationship Inventory (QRI) is a recently developed questionnaire to measure
      individual-specific social support. We developed the Japanese version by means of
      back translation and ascertained its reliability and validity among the Japanese
      women who had had two recurrent spontaneous abortions without known organic
      etiologies. Factor analysis revealed that the Japanese QRI had a two-factor
      structure, representing supportive and conflictual aspects of a particular
      relationship (named Factor-S and Factor-C, respectively). Each factor showed
      satisfactory reliability with Cronbach's alphas of 0.95 and 0.89. When the QRI
      scores were compared with the scales from the Social Support Questionnaire, a
      measure of general social support, the Factor-C of the former with respect to the
      mother correlated negatively with the Social Support Satisfaction of the latter
      (r = - 0.40; 95% confidence interval (CI) - 0.64 to - 0.09). Childhood
      experiences with parents also showed expected correlations with the QRI: care
      received from the parent before age 16 years strongly predicted Factor-S with
      that parent (r = 0.50, 95% CI 0.21-0.71 in the case of the mother; r = 0.54, 95%
      CI 0.27-0.73 in the case of the father). Although we still need to examine the
      Japanese QRI with different populations, it appears to be a promising measure of
      individual-specific relationship for the Japanese population.

PMID- 12193241
TI  - Relationships between seizure duration and seizure threshold and stimulus dosage
      at electroconvulsive therapy: implications for electroconvulsive therapy
      practice.
AB  - Recent studies cast doubt on the usefulness of seizure duration as an index for
      stimulus dosage adjustment at electroconvulsive therapy (ECT). A retrospective
      analysis on the relationships between seizure duration and seizure threshold and
      stimulus dosage was performed for 54 patients who received a standardized ECT
      dose titration and treatment protocol. Subjects receiving stimulus dosage at
      seizure threshold had a highly variable motor seizure duration, ranging from 15
      to 89 s, and 7.4% of subjects had seizures longer than 60 s. Regression analysis
      showed that initial seizure threshold and height were independent predictors of
      motor seizure duration during dose titration and accounted for 34% of its
      variance. Stimulus dosage was increased by 40-67% between the first and second
      ECT session; however, 60% of subjects had no lengthening of seizures and motor
      seizure duration was significantly shorter at the second treatment (mean +/- SD:
      35.7 +/- 12.3 vs 31.0 +/- 10.6 s; paired t = 2.9, d.f. = 34, P = 0.006). At the
      first and second ECT treatment, motor seizure duration was significantly related
      to stimulus dosage (r = -0.45 and r = -0.41, respectively). Given the negative
      correlation between seizure duration and stimulus intensity, a policy that
      recommends an increase of stimulus dosage and its reduction for patients with
      short and long seizures, respectively, does not necessarily result in 'optimal'
      seizure duration. A better dosing policy that places less emphasis on seizure
      duration is proposed.

PMID- 12193243
TI  - Can olanzapine be implicated in causing serotonin syndrome?
AB  - The present paper describes a case of serotonin syndrome (SS), which developed in
      a patient with bipolar affective disorder after the addition of olanzapine to her
      regimen of lithium and citalopram. This appears to be the first report that
      implicates olanzapine with SS. Clinicians should be aware of the risk of SS when
      adding atypical antipsychotics, such as olanzapine, to serotonergic agents.

PMID- 12193244
TI  - Depressive mixed state frequency: age/gender effects.
AB  - Depressive mixed state (DMX), a major depressive episode (MDE) combined with few
      manic/hypomanic symptoms, is understudied. Age and gender are important variables
      in mood disorders. The aim of the present study was to determine whether age and
      gender had any effect on the frequency of DMX. Consecutive unipolar (n = 144) and
      bipolar II (n = 218) drug-free MDE out-patients were interviewed with the
      Structured Clinical Interview for DSM-IV when presenting for MDE treatment. The
      presence of hypomanic symptoms during the index MDE was assessed systematically.
      Depressive mixed state was defined as a MDE with three or more concurrent
      hypomanic symptoms (DMX3), following previous reports. Associations were tested
      by logistic regression. The results showed that the DMX3 frequency was 43.9% and
      that it affected more females than males. Frequency decreased with age. The lower
      frequency with age was related to the lower frequency of bipolar II disorder with
      age. Bipolar disorder family history of DMX3 patients did not change with age. In
      conclusion, the frequency of DMX3 was high and related to age. The high frequency
      of DMX3 supports the clinical usefulness of the definition, as well as
      observations that antidepressants may worsen its hypomanic symptoms, whereas
      antipsychotics and mood stabilisers may treat them. A bipolar vulnerability seems
      to be required for the appearance of DMX3 also in later life.

PMID- 12193245
TI  - Blink rate variability in patients with panic disorder: new trial using
      audiovisual stimulation.
AB  - Several lines of evidence have implicated central dopaminergic pathways in the
      modulation of spontaneous blink rate (BR). Furthermore, previous studies have
      indicated a relationship between spontaneous BR and anxiety and/or depression.
      However, to our knowledge, there is no report on the examination of BR in a group
      of patients with panic disorder (PD). During the conditions of rest and with
      audiovisual stimulation, exposed to a video of imaginary experiences, such as
      driving a motor vehicle or diving into the sea, BR was examined in 11 male
      patients with PD and compared with the BR of 16 age-matched normal controls. The
      BR was significantly higher in PD patients relative to normal controls under both
      conditions. In particular, the PD group had a higher BR score during the sea
      scene as relaxation compared with the normal controls. In conclusion, although
      the sample size was small the present preliminary study, these findings suggest
      that BR may have potential for application in the assessment of anxiety state,
      which is consistent with previous studies.

PMID- 12193246
TI  - Reliability and validity of the Turkish version of the adolescent dissociative
      experiences scale.
AB  - The Adolescent Dissociative Experiences Scale (A-DES) is designed to measure
      dissociation in adolescents. The present study aimed to assess the reliability,
      validity, and psychometric characteristics of the Turkish version of the A-DES.
      The Turkish version of the A-DES was administered to 20 patients with a
      dissociative disorder, 24 patients with post-traumatic stress disorder (PTSD), 31
      patients with anxiety disorder, 31 patients with mood disorder, 24 patients with
      attention deficit-hyperactivity disorder (ADHD), and 201 non-clinical
      participants. The internal consistency and the test-retest correlation of the A
      DES were excellent. The mean total score of A-DES was 6.2 in dissociative
      disorder, 3.9 in PTSD, 2.1 in anxiety disorder, 2.4 in mood disorder, 2.5 in ADHD
      groups and 2.4 in non-clinical participants. There was a statistically
      significant difference between dissociative patients and other diagnostic groups
      on the A-DES total score. The good psychometric characteristics of the A-DES
      among Turkish participants support its cross-cultural validity.

PMID- 12193247
TI  - Pathological effect of seizures on the hippocampus in cases with temporal lobe
      epilepsy caused by brain tumors.
AB  - The cause of Ammon's horn sclerosis in temporal lobe epilepsy has not yet been
      clarified. In the present study, the pathological effect of epileptic seizures on
      the hippocampus was investigated in surgically treated patients with brain tumor
      induced temporal lobe epilepsy. Tumors involving the hippocampus were identified
      as the foci of epilepsy in 13 patients (seven male and six female) and resected
      after epileptic discharges were found at the hippocampus on intraoperative
      electrocorticogram. The mean age at operation was 29.8 +/- 11.5 years and the
      mean age of seizure onset was 19.9 +/- 10.8 years. Because only three of the 13
      patients who underwent temporal lobectomy for brain tumors involving the
      hippocampus had Ammon's horn sclerosis pathologically, it was concluded that it
      was very unlikely that the Ammon's horn sclerosis was produced by the epileptic
      seizures. Two of the three patients with pathological signs of Ammon's horn
      sclerosis had episodes of coma, covulsion, high fever and cyanosis in their past
      histories that might have portended the appearance of Ammon's horn sclerosis
      later in their lives.

PMID- 12193248
TI  - Perirhinal cortical lesion suppresses the secondary generalization in kainic acid
      induced limbic seizure.
AB  - To elucidate the role of the perirhinal cortex (PRC) in experimental epilepsy,
      the effects of the lesion of the PRC on kainic acid (KA)-induced limbic seizure
      were investigated. The PRC lesion was made by means of ibotenic acid (IBO)
      microinjection. The electroencephalogram in the PRC-lesioned rats demonstrated
      suppression of the propagation of epileptic discharges from the limbic structures
      to the sensorimotor cortex. Behaviorally, motor manifestations such as
      mastication, facial twitching and forelimb clonus were attenuated. These results
      indicate that the PRC seems to be a potent relay station of the secondary
      generalization from the limbic structures to the sensorimotor cortex.

PMID- 12193249
TI  - Concordance between self- and observer-ratings on Kasahara's Inventory for the
      Melancholic Type Personality.
AB  - The concordance between self- and observer-ratings was investigated for items on
      Kasahara's Inventory for the Melancholic Type Personality (KIMTP). Subjects
      consisted of 44 patients diagnosed with an ICD-10 diagnostic criteria for
      research (DCR) depressive episode (F32) or recurrent depressive disorder (F33)
      unipolar affective disorder, and 44 observers. Thirty-one of the 44 patients were
      diagnosed with endogenous depression. The observers consisted of five parents,
      eight children, thre siblings, 25 spouses, and three partners. Concordance was
      tested with Student's paired t-test and one-way analysis of variance intraclass
      correlation coefficient (ANOVA ICC). There was no statistical difference between
      the mean total self-rating score and the mean total observer-rating score in the
      endogenous depression group, but the mean total self-rating score was
      significantly higher than the mean total observer-rating score in the non
      endogenous depression group. When the self and observer tests in this non
      endogenous depression group were compared on an item-by-item basis, most items
      tended to receive higher scores from the self-raters than from the observer
      raters. The ICC had good concordance for mean total self- and observer-ratings in
      the endogenous depression group but not the non-endogenous depression group. On
      an item-by-item basis, concordance was high between self- and observer-raters for
      more items in the endogenous depression group than in the non-endogenous
      depression group. There were some important differences between self- and
      observer-ratings for certain items in the non-endogenous depression group.
      Patients in this group tended to give higher scores to items representing Typus
      melancholicus in relation to scores given by observers.

PMID- 12193250
TI  - Mental health conditions among atomic bomb survivors in Nagasaki.
AB  - To elucidate the effects of the bombing on the atomic bomb survivors' mental
      health, a mental health survey was conducted using a 12-item version of the
      General Health Questionnaire (GHQ-12) and a mail survey on atomic bomb exposure
      conditions and lifestyle using a self-administered questionnaire. A total of 3526
      atomic bomb survivors in Nagasaki responded and a high GHQ-12 score, as defined
      when the responses to four or more items were positive, was observed in 296
      (8.4%) subjects. It was indicated that the risk of a high GHQ-12 score will
      decrease 0.98-fold with every 1-year increase in age, and will increase 1.45-fold
      and 1.70-fold in those who lost family members due to the bombing and those who
      had acute symptoms, respectively, compared with those who did not. It was
      indicated that the atomic bomb exposure has affected survivors' mental health and
      that the care of their mental health is important.

PMID- 12193251
TI  - Serial magnetic resonance angiography in cerebral infarction after varicella
      infection.
AB  - The case of a 1-year-8-month-old-boy with cerebral infarction after varicella
      infection is reported here. Brain magnetic resonance (MR) angiography revealed
      segmental narrowing of the left middle cerebral artery which became normal 8
      months later. The MR angiography well demonstrated the time course of the
      vascular involvement in the present patient. In cerebral infarction after
      varicella infection, the proximal portion of the main cerebral arteries were
      frequently damaged therefore MR angiography is useful for diagnosis and
      therapeutic decision-making. Moreover, serial MR angiographic studies can clarify
      the natural course of vascular changes in varicella virus-related cerebral
      infarction.

PMID- 12193253
TI  - Pain diary as a treatment tool for patients with numbness, pain and mood
      disturbance.

PMID- 12193252
TI  - A 5-year-old boy with recurrent mania successfully treated with carbamazepine.
AB  - In the present paper the clinical symptomatology and treatment of childhood mania
      that was first seen in a child at 5 years of age and which re-emerged at age 7,
      is reported. The patient presented at the child and adolescent psychiatric
      outpatient clinic of Istanbul Medical University with the typical symptoms of
      mania such of hyperactivity, euphoria, irritability, dangerous and risky
      behavior, decreased sleep, and age-inappropriate sexual behavior. He was treated
      with carbamazepine safely and effectively without any major side-effects.
      Clinical phenomenology and treatment of the condition are discussed with relevant
      literature.

PMID- 12193254
TI  - Receptor-mediated hepatocarcinogenesis: role of hepatocyte proliferation and
      apoptosis.
AB  - The rodent liver is a target organ for the action of several non-genotoxic
      carcinogens. These include dioxins, polychlorinated biphenyls, phenobarbital,
      peroxisome proliferators and organochlorine pesticides. These chemicals disrupt
      the homeostasis of the liver by perturbing hepatocyte cell death and
      proliferation, causing hyperplasia leading to tumour formation. Significant
      progress has been made towards elucidating the mechanisms of action of these
      toxicants since the discovery of receptors that bind specific classes of
      xenobiotics. Dioxins and polychlorinated biphenyls bind to the aryl hydrocarbon
      receptor, phenobarbital binds to the constitutive androstane receptor and
      peroxisome proliferators act via the their activated receptor alpha. These three
      receptors have ligand-dependent transcription activities and therefore mediate
      changes in gene expression in response to toxicant exposure. The development of
      transgenic mouse strains where the genes for these receptors are disrupted has
      demonstrated that receptor activity is essential for the toxicity of these
      carcinogens. This implies that changes in the expression of key target genes
      control proliferation and apoptosis in the xenobiotic-induced hepatocyte
      phenotype.

PMID- 12193255
TI  - Long-term physical exercise and atrial natriuretic peptide in obese Zucker rats.
AB  - Endurance training increases natriuretic peptide synthesis in the hypertrophied
      myocardium of spontaneously hypertensive rats. We examined the effects of 22-week
      long treadmill exercise on plasma and tissue atrial natriuretic peptide in Zucker
      rats, a model of genetic obesity and moderate hypertension without clear cardiac
      hypertrophy. The blood pressures of the animals were measured by the tail-cuff
      method, and plasma and tissue samples for the peptide determinations were taken
      at the end of the study. The training increased heart weight to body weight
      ratio, while atrial natriuretic peptide contents in the right and left atrium,
      ventricular tissue, and plasma did not change. The exercise prevented the
      elevation of blood pressure, which was observed in non-exercised obese Zucker
      rats, and also reduced blood pressure in the lean rats. In conclusion, these
      results suggest that in the absence of preceding myocardial hypertrophy, the long
      term exercise-induced workload is not deleterious to the heart in experimental
      obesity, since no changes in plasma and tissue atrial natriuretic peptide were
      detected.

PMID- 12193256
TI  - Tamoxifen induces changes in the lipid composition of the retinal pigment
      epithelium cell line D407.
AB  - Tamoxifen, the antioestrogenic drug prescribed for long-term, low-dose therapy of
      breast cancer, induces retinopathy. This study evaluates the effects of tamoxifen
      on the human retinal pigment epithelial cell line D407, attempting to identify
      the underlying mechanisms on tamoxifen-induced retinopathy and the involvement of
      cellular membranes in the cytotoxic action mechanism. We demonstrate that the
      tamoxifen-induced decrease in the cell growth of the D407 cell line results from
      pyknosis and cell cycle arrest rather than from necrosis. Furthermore, D407 cells
      influence the lipid composition of both plasma membrane and intracellular
      membranes in response to tamoxifen. Tamoxifen increases the physical order of the
      lipid bilayer. We observed a compensatory decrease in the cholesterol content of
      the plasma membrane which results in an increase of the plasma membrane fluidity.
      In intracellular membranes the phosphatidylcholine content is reduced to 50% of
      the controls. This reduction may be related to the formation of a second
      messenger via phospholipase pathway and sustained activation of protein kinase C.
      Since increased plasma membrane fluidity as well as sustained activation of
      protein kinase C influence the rod outer segments binding and/or ingestion by
      retinal pigment epithelial cells, our results suggest that membrane-mediated
      pathways contribute to the tamoxifen-induced retinopathy.

PMID- 12193257
TI  - Diacerhein and rhein prevent interleukin-1beta-induced nuclear factor-kappaB
      activation by inhibiting the degradation of inhibitor kappaB-alpha.
AB  - Diacerhein and rhein are anthraquinone compounds that ameliorate the course of
      osteoarthritis. Recent reports also suggest that these compounds may have
      antiinflammatory properties, but the cellular mechanisms by which they exert
      antiosteoarthritic and possibly antiinflammatory effects are still incompletely
      understood. The purpose of this study was to investigate the ability of
      diacerhein and rhein to inhibit the activation of the transcription factor
      nuclear factor kappaB, induced by the proinflammatory cytokine interleukin-1beta,
      in primary monolayer cultures of bovine articular chondrocytes. We also studied
      the ability of diacerhein and rhein to prevent the expression of the inducible
      nitric oxide synthase gene, which is driven by nuclear factor-kappaB. We observed
      that interleukin-1beta induced the degradation of the inhibitor kappaB-alpha
      protein and the translocation of the protein p65 (a member of the nuclear factor
      kappaB family) to the nucleus, which were inhibited by diacerhein and rhein, in a
      dose-dependent manner. Interleukin-1beta-induced nuclear factor-kappaB binding to
      a specific (gamma-(32)P)-labelled oligonucleotide probe was also inhibited by
      treatment of chondrocytes with diacerhein or rhein, as revealed by
      electrophoretic mobility shift assay. Inducible nitric oxide synthase mRNA and
      protein synthesis and nitric oxide production were also inhibited by diacerhein
      and rhein, in a dose-dependent manner. The half-maximal inhibitory concentrations
      of diacerhein and rhein, relative to nitric oxide production, were 8.2 microM
      ;and 7.7 microM, respectively. These results suggest that diacerhein and rhein
      inhibit nuclear factor-kappaB activation and, consequently, the expression of
      nuclear factor-kappaB-dependent genes, such as the inducible nitric oxide
      synthase gene, which can explain their antiosteoarthritic and antiinflammatory
      effects.

PMID- 12193258
TI  - Ecstasy during loud noise exposure induces dramatic ultrastructural changes in
      the heart.
AB  - The acute toxicity induced by 3,4-methylenedioxymethamphetamine appears as
      rabdomyolysis involving the myocardium (myocytolysis) and it is often suspected
      to be responsible for sudden death. In line with this, cardiac symptoms such as
      tachycardia, hypertension, and arrhythmia are present in persons abusing ecstasy.
      In most cases, ecstasy is abused in loud noise, which in itself might affect the
      myocardium. To our knowledge no study has investigated the concomitant exposure
      to ecstasy and loud noise in order to evaluate the role of the loud noise in
      modulating MDMA toxicity. In the present study, we analyzed whether cardiac
      effects following a typical "binging" pattern of MDMA administration are enhanced
      by concomitant exposure to loud noise. Our findings did not show any myocardial
      lesion detectable under light microscopy. In contrast, alterations were visible
      at the ultrastructural level as mitochondrial changes. In particular, we found a
      marked enhancement in the number of altered mitochondria when MDMA was
      administered during exposure to loud noise.

PMID- 12193259
TI  - Effect of the anti-breast cancer drug tamoxifen on Ca(2+) movement in human
      osteosarcoma cells.
AB  - The anti-breast cancer drug tamoxifen has recently been shown to cause an
      increase in [Ca(2+)]i in renal tubular cells, breast cells and bladder cells.
      Because tamoxifen is known to interact with oestrogens leading to modulation of
      bone metabolism, the present study was aimed at exploring whether tamoxifen could
      alter Ca(2+) signaling in human osteoblast-like MG63 cells. Cytosolic free Ca(2+)
      levels were recorded by using the Ca(2+)-sensitive dye fura-2. Tamoxifen induced
      a sustained [Ca(2+)]i increase at concentrations above 1 microM with an EC(50) of
      8 microM. Removal of extracellular Ca(2+) reduced the response by 40%, suggesting
      that tamoxifen induced both Ca(2+) influx and store Ca(2+) release. Tamoxifen
      induced Ca(2+) influx was confirmed as tamoxifen caused Mn(2+) influx-induced
      quench of fura-2 fluorescence. In Ca(2+)-free medium, pretreatment with 10 microM
      tamoxifen abolished the [Ca(2+)]i increase induced by 1 microM thapsigargin (an
      endoplasmic reticulum Ca(2+) pump inhibitor), and by 2 microM carbonylcyanide m
      chlorophenylhydrazone (a mitochondrial uncoupler). Conversely, pretreatment with
      thapsigargin and carbonylcyanide m-chlorophenylhydrazone only reduced 64% of
      tamoxifen-induced [Ca(2+)]i increases. Addition of 2 microM U73122 to inhibit
      phospholipase C activity abolished the [Ca(2+)]i increase induced by 1 microM
      histamine, a phospholipase C-dependent Ca(2+) mobilizer, without affecting 10
      microM tamoxifen-induced Ca(2+) release. The [Ca(2+)]i increase induced by 10
      microM tamoxifen was not altered by 10 microM of nifedipine, verapamil and
      diltiazem. Together, the data show that tamoxifen induced a lasting increase in
      [Ca(2+)]i in human osteoblast-like cells by causing Ca(2+) influx and releasing
      Ca(2+) from multiple stores in a phospholipase C-independent manner.

PMID- 12193260
TI  - Imperatorin, a furanocoumarin from Angelica dahurica (Umbelliferae), induces
      cytochrome c-dependent apoptosis in human promyelocytic leukaemia, HL-60 Cells.
AB  - Imperatorin, a biologically active furanocoumarin from the roots of Angelica
      dahurica (Umbelliferae), was found to induce apoptosis in human promyelocytic
      leukaemia, HL-60 cells. DNA fragmentation assay, morphology-based evaluation, and
      flow cytometric analysis demonstrated that imperatorin at micromolar
      concentrations was able to trigger apoptosis of HL-60 cells. Neither necrosis nor
      differentiation was observed at cytotoxic micromolar concentrations of
      imperatorin. Further studies showed that the cytochrome c/caspase-9 pathway was
      responsible for imperatorin-induced apoptosis; i.e., mitochondrial membrane was
      depolarized, Bcl-2 was down-regulated, cytochrome c was released from
      mitochondria, caspase-9 and caspase-3 were activated, and poly(ADP-ribose)
      polymerase was cleaved. Furthermore, imperatorin-induced apoptosis was
      significantly blocked by Z-VAD-FMK (a broad spectrum caspase inhibitor), Z-LEHD
      FMK (a caspase-9 inhibitor) and Ac-DMQD-CHO (a caspase-3 inhibitor), but not by Z
      IEDT-FMK (a caspase-8 inhibitor).

PMID- 12193261
TI  - The outcome of endodontic resurgery: a systematic review.
AB  - AIM: The aim of this paper is to establish an outcome standard for the assessment
      of healing radiographically after resurgery of persistent periradicular lesions
      by systematically reviewing the results from published studies. METHODOLOGY: The
      systematic review process requires the definition of predetermined criteria
      delineating the inclusion parameters of studies reviewed. Of 42 papers that were
      reviewed, eight qualified for inclusion. A weighted-average was calculated from
      the results taken from the eight eligible, peer-reviewed studies, published
      between 1970 and 1997. RESULTS: Three hundred and thirty patients out of 2375
      (14%) from the included studies underwent resurgery for failure of healing as
      determined radiographically. Of this population, 35.7% healed successfully after
      resurgery, 26.3% healed with uncertain results and 38% did not heal at the one
      year follow-up. CONCLUSIONS: Although there is nearly equal distribution of
      results between all categories, a 35.7% rate of healing as assessed
      radiographically is essentially equivalent to the 38% failure rate. This paper
      will allow an evaluation of current research results to establish an outcome
      standard and enable techniques and filling materials to be evaluated and
      compared. Furthermore, the outcome standard can assist in defining demographic
      and aetiological factors that contribute to the potential outcome of resurgery
      cases.

PMID- 12193262
TI  - Effect of access cavity location and design on degree and distribution of
      instrumented root canal surface in maxillary anterior teeth.
AB  - AIM: The null hypothesis tested in this study was that in single-rooted anterior
      teeth with simple root canal anatomy, different access cavity designs ('lingual
      cingulum', 'lingual conventional', 'incisal straight-line') do not influence the
      ability of endodontic files to plane the walls of the root canals. METHODOLOGY:
      Thirty extracted human maxillary anterior teeth were divided randomly into three
      groups for each access cavity. The access cavities were prepared according to
      predefined criteria and the roots embedded in individual polyvinyl-siloxane putty
      matrices. The matrices allowed these teeth to be split into buccal and palatal
      halves and to be reassembled. The split teeth enabled removal of pulpal remnants
      from the root canal system and the walls to be stained with an even layer of
      permanent black ink. Once dried, the split roots were reassembled in the putty
      matrices and a step-back filing technique was used to prepare the canals with
      water irrigation. The canal walls were examined for residual ink staining and
      scored by three independent assessors using an index devised for the purpose.
      RESULTS: There was good agreement between the assessors. None of the access
      cavities allowed file contact with the entire root canal wall. The overall
      (palatal and buccal sections) scores showed significant differences (P < 0.01)
      between the access cavity groups in the extent to which the canal walls could be
      filed. The straight-line incisal access cavity had the greatest proportion of
      instrumented root canal surface. The lingual cingulum access cavity was the worst
      in this respect. The differences in residual ink scores between the access cavity
      types were significant for the buccal halves (P < 0.01) but not for the palatal
      halves (P > 0.05). CONCLUSIONS: The null hypothesis was proven. Regardless of
      access cavity design, mechanical preparation did not allow instrumentation of the
      entire root canal wall. Straight-line access allowed the greatest proportion of
      the root canal wall to be instrumented and the lingual cingulum access the least.

PMID- 12193263
TI  - Inactivation of root canal medicaments by dentine, hydroxylapatite and bovine
      serum albumin.
AB  - AIM: This study examined and compared the inhibition of the antibacterial effect
      of saturated calcium hydroxide solution, chlorhexidine acetate and iodine
      potassium iodide by dentine, hydroxylapatite and bovine serum albumin.
      METHODOLOGY: Enterococcus faecalis strain A197A prepared to a suspension of 3 x
      10(8) cells per ml in 0.5% peptone water was used. Fifty microL of saturated
      calcium hydroxide solution, 0.05% chlorhexidine acetate or 0.2/0.4% iodine
      potassium iodide were incubated at 37 degrees C with 28 mg dentine powder (DP),
      hydroxylapatite (HA) or bovine serum albumin (BSA) in 50 microL water for 1 h
      before adding 50 microL of the bacterial suspension. Samples for bacterial
      culturing were taken from the suspension 1 and 24 h after adding the bacteria. In
      further experiments, the amount of dentine was stepwise reduced from 28 mg 150
      microL-1 to 2.8 mg 150 microL-1. RESULTS: Calcium hydroxide was totally
      inactivated by the presence of 28 mg of DP, HA or BSA. Chlorhexidine (0.05%) was
      strongly inhibited by BSA and slowed down by dentine. However, HA had little or
      no inhibitory effect on chlorhexidine. The antibacterial effect of 0.2/0.4%
      iodine potassium iodide on E. faecalis was totally inhibited by dentine (28 mg),
      but was practically unaffected by HA or BSA. A stepwise reduction of dentine from
      28 mg 150 microL-1 to 2.8 mg 150 microL-1 was followed by a similar reduction of
      the inhibition of the antibacterial activity of chlorhexidine. Iodine potassium
      iodide was not inhibited at all with dentine amounts less than 28 mg. However,
      the effect of saturated calcium hydroxide solution was totally eliminated by
      dentine, in all four concentrations. CONCLUSION: Inhibition by dentine of the
      antibacterial activity of calcium hydroxide, chlorhexidine and iodine potassium
      iodide occurs by different mechanisms. Different components of dentine may be
      responsible for the inhibition of these three medicaments. Calcium hydroxide was
      particularly sensitive to inhibition by both inorganic and organic compounds.

PMID- 12193264
TI  - The use of calcium sulphate in the surgical treatment of a 'through and through'
      periradicular lesion.
AB  - AIM: This randomized, controlled, clinical study was designed to evaluate the
      adjunctive effect of calcium sulphate grafts on the surgical treatment of through
      and through periradicular lesions. METHODOLOGY: Twenty patients each with one
      tooth showing evidence radiologically of a periradicular lesion wider than 10 mm,
      with lack of both buccal and lingual cortical bony plates and an indication for
      surgery were selected for the study. Ten teeth were treated with apicectomy, root
      end filling and grafting of the bone defect with calcium sulphate prior to
      suturing (test group). The other 10 teeth received the same surgical therapy but
      no grafting with calcium sulphate (control group). The outcome of the healing
      process was evaluated at 6 and 12 months radiographically following the criteria
      reported by Rud and Andreasen. RESULTS: At the six- and 12-month evaluation the
      test group had seven teeth with complete healing and two with incomplete healing,
      whilst the control group showed three teeth with complete healing, five with
      incomplete healing and one with unsatisfactory healing. One tooth in each group
      had to be extracted because of a vertical fracture that occurred during the
      follow-up period. CONCLUSIONS: The results of the study demonstrate that the
      addition of calcium sulphate as a bone graft during the conventional surgical
      treatment of through and through lesions improves the clinical outcome.
      Histological analysis is desirable to investigate the quality of tissues formed
      using the two surgical procedures.

PMID- 12193265
TI  - Frequency and distribution of endodontically treated teeth and apical
      periodontitis in an urban Danish population.
AB  - AIM: The aim of this study was to investigate the prevalence of endodontically
      treated teeth and apical periodontitis (AP) in a Danish population. METHODOLOGY:
      From Aarhus County 614 individuals were radiographically examined, and the
      frequency of endodontic treatment and periapical status of all teeth were
      assessed. The year of birth of the subjects ranged from 1935 to 1975. The chi
      squared test was used to determine the significance of differences between males
      and females and amongst age and tooth groups for the following parameters: AP,
      the number of endodontically treated teeth, and the number of endodontically
      treated teeth with AP. RESULTS: A total of 15 984 teeth were examined; of these
      538 (3.4%) had AP and 773 (4.8%) had been endodontically treated. Of the
      endodontically treated teeth, 404 (52.2%) had AP. Females had more endodontically
      treated teeth than males; otherwise, no effect of gender was observed.
      Significantly more molars (P < 0.01) had been endodontically treated (8.1%)
      compared to premolars (5.4%) and anterior teeth (2.5%). The prevalence of AP in
      connection with molars was significantly (P < 0.01) higher (7.0%) than premolars
      (2.8%) and anterior teeth (1.5%). The prevalence of endodontically treated teeth
      and of teeth with AP gradually increased with age. CONCLUSIONS: The average
      number of teeth, the number of teeth with AP and the number of teeth with
      endodontic treatment in Danish adults were comparable to findings in other
      European countries. The frequency of endodontically treated teeth with AP was
      found to be high compared to that demonstrated in other epidemiological studies.

PMID- 12193266
TI  - Some factors affecting the concentration of available chlorine in commercial
      sources of sodium hypochlorite.
AB  - AIMS: To evaluate the availability, effect of storage, dilution and heating on
      some commercial sources of sodium hypochlorite (NaOCl). METHODOLOGY: All
      pharmacies in a Regional Health Authority were telephone surveyed to establish
      the proprietary and nonproprietary NaOCl products available, their cost and
      concentration. Ninety-six freshly produced bottles of a commercially available
      thin household bleach (J. Sainsbury's) were randomly stored in four different
      modes (full 1 L bottles in dark at room temperature, half-empty 1 L bottles under
      the same conditions, full 200 mL bottles under the same conditions, full 200 mL
      bottles stored at 37 degrees C) up to 6 months. The available chlorine in the
      bleach solutions was evaluated at specific time intervals (0, 1, 2 weeks, 1, 2,
      3, 4, 6 months) using iodometric titration. Four brands of commercially available
      bleaches (J. Sainsbury's Thin Household Bleach, Tesco's Value Bleach, Tesco's Red
      Label Bleach, Safeway's Savers Bleach) were diluted (by 1 : 1, 1 : 2 or 1 : 3
      dilution factors) and samples taken from each dilution for titration to test
      predictability. NaOCl solutions (5% w/w) were heated in covered or uncovered
      beakers up to 60-85 degrees C. Samples were taken from each beaker at time 0 and
      each h up to 4 h, for titration. RESULTS: Of the 116 pharmacies, 33% could supply
      a proprietary product and 53% a nonproprietary product. In all, 78% were able to
      supply a NaOCl product. There was no significant difference (P < 0.05) in
      available chlorine at baseline between the different modes of storage. After
      storage at room temperature for 6 months, there were no significant differences
      (3% of original; P > 0.05) between the different modes of storage. When the
      storage temperature was 37 degrees C, however, there was a significant difference
      (38% of original; P < 0.01) at 6 months. Comparison of baseline with the
      concentrations of available chlorine at 6 months showed significant differences
      (P < 0.01) for all conditions. The available chlorine concentration in four
      brands of 'thin' supermarket bleaches could be predictably reduced according to
      the dilution factor. When 5% NaOCl was heated to 60-85 degrees C for up to 4 h,
      the available chlorine was increased to 6% in covered solutions and 9% in
      uncovered solutions. CONCLUSIONS: Both proprietary and nonproprietary solutions
      of NaOCl should be relatively easily obtainable in the UK. Stored under
      appropriate conditions, commercially available thin bleaches and nonproprietary
      solutions of NaOCl may be diluted to obtain predictable concentrations. Heating
      solutions of NaOCl may cause unpredictable changes to the concentration,
      depending upon conditions.

PMID- 12193267
TI  - Bacteria on the apical root surfaces of untreated teeth with periradicular
      lesions: a scanning electron microscopy study.
AB  - AIM: The purpose of this study was to examine the presence of bacteria on the
      apical root surfaces of untreated teeth associated with chronic periradicular
      lesions. METHODOLOGY: Twenty-seven extracted teeth with extensive carious
      lesions, radiolucent lesions of varying sizes and attached periradicular lesions
      after extraction, were selected for study. Following fixation, lesions were
      removed and the apical 5-mm portion of each root was sectioned. Root tips were
      dehydrated, sputter-coated with gold, and then examined for the occurrence of
      bacteria on the apical root surfaces using a scanning electron microscope.
      RESULTS: Bacterial cells were usually observed close to the apical foramen, but
      restricted to the root canal. Morphologically, these bacteria consisted of cocci
      and rods. A dense bacterial aggregate composed mainly of rods was observed within
      the root canal and surrounding the apical foramen of one specimen. Beyond the
      apical foramen, other bacterial morphological types were recognized, including
      coaggregations of cocci and filaments, characterizing a fully developed 'corn
      cob'. CONCLUSIONS: Extraradicular bacteria were observed in one tooth out of 27
      (4% of the cases).

PMID- 12193268
TI  - Effects of four Ni-Ti preparation techniques on root canal geometry assessed by
      micro computed tomography.
AB  - AIM: The aim of this study was to compare the effects of four preparation
      techniques on canal volume and surface area using three-dimensionally
      reconstructed root canals in extracted human maxillary molars. In addition, micro
      CT data was used to describe morphometric parameters related to the four
      preparation techniques. METHODOLOGY: A micro computed tomography scanner was used
      to analyse root canals in extracted maxillary molars. Specimens were scanned
      before and after canals were prepared using Ni-Ti - K-Files, Lightspeed
      instruments, ProFile.04 and GT rotary instruments. Differences in dentine volume
      removed, canal straightening, the proportion of unchanged area and canal
      transportation were calculated using specially developed software. RESULTS:
      Instrumentation of canals increased volume and surface area. Prepared canals were
      significantly more rounded, had greater diameters and were straighter than
      unprepared canals. However, all instrumentation techniques left 35% or more of
      the canals' surface area unchanged. Whilst there were significant differences
      between the three canal types investigated, very few differences were found with
      respect to instrument types. CONCLUSIONS: Within the limitations of the micro CT
      system, there were few differences between the four canal instrumentation
      techniques used. By contrast, a strong impact of variations of canal anatomy was
      demonstrated. Further studies with 3D-techniques are required to fully understand
      the biomechanical aspects of root canal preparation.

PMID- 12193269
TI  - The influence of two concentrations of sodium hypochlorite on human blood:
      changes in haemolysis, pH and protein.
AB  - AIM: To evaluate the in vitro effect of 2.5% and 5.0% sodium hypochlorite (NaOCl)
      on human blood. METHODOLOGY: Each concentration of NaOCl was reacted with human
      blood for 5 min at volume ratios of 1 : 1, 1 : 6, 1 : 12, each creating changes
      in colour, pH and temperature. Reaction suspensions were separated by
      centrifugation, and absorption measurements made for separated bilirubin, Fe, and
      protein supernatants. Each supernatant was desalted, lyophilized, and treated by
      SDS polyacrylamide gel electrophoresis (SOS-PAGE). RESULTS: Increased ratios and
      concentrations of NaOCl caused an increase in both pH and temperature. Protein
      supernatants tended to decompose on SDS-PAGE. Supernatants showed increased
      decolourisation with 5.0% NaOCl. Concentrations of bilirubin, Ferrum and protein
      in supernatants decreased with increased NaOCl concentration. NaOCl had an effect
      on the protein component in blood. CONCLUSIONS: These data suggest that changes
      in molecular structure are due to the chemical effects of NaOCl. Protein bands
      tended to show low molecular weight, suggesting that haemoglobin components
      effect the oxidation-reduction reaction.

PMID- 12193270
TI  - Antimicrobial effectiveness of electro-chemically activated water as an
      endodontic irrigation solution.
AB  - AIM: The aim of this in vitro study was to evaluate the antimicrobial
      effectiveness of electro-chemically activated water (ECA) as an endodontic
      irrigation solution. METHODOLOGY: The root canals of 60 caries-free, single
      rooted, adult, maxillary, anterior human teeth were instrumented and irrigated in
      a similar method to that used for in vivo root canal treatment. The external root
      surface of each tooth was sealed, maintaining the access cavities patent and the
      root canals were inoculated with a suspension containing four bacteria. The teeth
      were randomly divided into four groups (n = 15). Each group was irrigated
      ultrasonically with one of the following solutions: distilled water (control),
      NaOCl (3.5%), and ECA, the latter at pHs 7.0 and 9.0. Antimicrobial effectiveness
      was established directly after irrigation and again 7 days later, by counting
      colony-forming units on blood agar plates and by spectrophotometric analysis.
      RESULTS: Large numbers of bacteria were present in the canals of teeth irrigated
      with distilled water. No bacteria were observed following irrigation with NaOCl.
      Neither of the ECA solutions were found to be effective against all the bacteria.
      Although some reduction in the number of bacteria was evident in the ECA groups,
      this was not statistically significant (P > 0.05) when compared to sodium
      hypochlorite. CONCLUSION: Within the confines of this study ECA did not
      demonstrate antimicrobial effectiveness.

PMID- 12193271
TI  - The kappa B transcriptional enhancer motif and signal sequences of V(D)J
      recombination are targets for the zinc finger protein HIVEP3/KRC: a site
      selection amplification binding study.
AB  - BACKGROUND: The ZAS family is composed of proteins that regulate transcription
      via specific gene regulatory elements. The amino-DNA binding domain (ZAS-N) and
      the carboxyl-DNA binding domain (ZAS-C) of a representative family member, named
      kappaB DNA binding and recognition component (KRC), were expressed as fusion
      proteins and their target DNA sequences were elucidated by site selection
      amplification binding assays, followed by cloning and DNA sequencing. The fusion
      proteins-selected DNA sequences were analyzed by the MEME and MAST computer
      programs to obtain consensus motifs and DNA elements bound by the ZAS domains.
      RESULTS: Both fusion proteins selected sequences that were similar to the kappaB
      motif or the canonical elements of the V(D)J recombination signal sequences (RSS)
      from a pool of degenerate oligonucleotides. Specifically, the ZAS-N domain
      selected sequences similar to the canonical RSS nonamer, while ZAS-C domain
      selected sequences similar to the canonical RSS heptamer. In addition, both KRC
      fusion proteins selected oligonucleoties with sequences identical to heptamer and
      nonamer sequences within endogenous RSS. CONCLUSIONS: The RSS are cis-acting DNA
      motifs which are essential for V(D)J recombination of antigen receptor genes. Due
      to its specific binding affinity for RSS and kappaB-like transcription enhancer
      motifs, we hypothesize that KRC may be involved in the regulation of V(D)J
      recombination.

PMID- 12193272
TI  - Native interface of the SAM domain polymer of TEL.
AB  - BACKGROUND: TEL is a transcriptional repressor containing a SAM domain that forms
      a helical polymer. In a number of hematologic malignancies, chromosomal
      translocations lead to aberrant fusions of TEL-SAM to a variety of other
      proteins, including many tyrosine kinases. TEL-SAM polymerization results in
      constitutive activation of the tyrosine kinase domains to which it becomes fused,
      leading to cell transformation. Thus, inhibitors of TEL-SAM self-association
      could abrogate transformation in these cells. In previous work, we determined the
      structure of a mutant TEL-SAM polymer bearing a Val to Glu substitution in center
      of the subunit interface. It remained unclear how much the mutation affected the
      architecture of the polymer, however. RESULTS: Here we determine the structure of
      the native polymer interface. To accomplish this goal, we introduced mutations
      that block polymer extension, producing a heterodimer with a wild-type interface.
      We find that the structure of the wild-type polymer interface is quite similar to
      the mutant structure determined previously. With the structure of the native
      interface, it is possible to evaluate the potential for developing therapeutic
      inhibitors of the interaction. We find that the interacting surfaces of the
      protein are relatively flat, containing no obvious pockets for the design of
      small molecule inhibitors. CONCLUSION: Our results confirm the architecture of
      the TEL-SAM polymer proposed previously based on a mutant structure. The fact
      that the interface contains no obvious potential binding pockets suggests that it
      may be difficult to find small molecule inhibitors to treat malignancies in this
      way.

PMID- 12193274
TI  - Analyses of Streptococcus mutans in saliva with species-specific monoclonal
      antibodies.
AB  - Three species-specific monoclonal antibodies (MAbs) against Streptococcus mutans
      were used to detect and quantify S. mutans levels in saliva. This study shows
      that MAb-based salivary S. mutans tests exhibit significantly higher specificity
      and sensitivity than the commonly used selective culture method. Examination of
      nearly 2,000 human saliva samples shows that S. mutans counts in human saliva
      vary from less than 10,000 to a high 36 million cells/mL. Over 15% of the saliva
      samples examined have salivary S. mutans counts over 500,000 cells/mL. When
      saliva samples were collected at different time points during a day, the number
      of salivary S. mutans in the same human subject varied, especially before and
      after sugar uptake. Additionally, data obtained from stimulated versus
      unstimulated saliva in the same human subjects differed greatly and appear to be
      completely uncorrelated. This study provides useful information and tools for
      analyzing the role of S. mutans in human dental caries.

PMID- 12193273
TI  - Delineation of RAID1, the RACK1 interaction domain located within the unique N
      terminal region of the cAMP-specific phosphodiesterase, PDE4D5.
AB  - BACKGROUND: The cyclic AMP specific phosphodiesterase, PDE4D5 interacts with the
      beta-propeller protein RACK1 to form a signaling scaffold complex in cells. Two
      hybrid analysis of truncation and mutant constructs of the unique N-terminal
      region of the cAMP-specific phosphodiesterase, PDE4D5 were used to define a
      domain conferring interaction with the signaling scaffold protein, RACK1.
      RESULTS: Truncation and mutagenesis approaches showed that the RACK1-interacting
      domain on PDE4D5 comprised a cluster of residues provided by Asn-22/Pro-23/Trp
      24/Asn-26 together with a series of hydrophobic amino acids, namely Leu-29, Val
      30, Leu-33, Leu-37 and Leu-38 in a 'Leu-Xaa-Xaa-Xaa-Leu' repeat. This was done by
      2-hybrid analyses and then confirmed in biochemical pull down analyses using GST
      RACK1 and mutant PDE4D5 forms expressed in COS cells. Mutation of Arg-34, to
      alanine, in PDE4D5 attenuated its interaction with RACK1 both in 2-hybrid screens
      and in pull down analyses. A 38-mer peptide, whose sequence reflected residues 12
      through 49 of PDE4D5, bound to RACK1 with similar affinity to native PDE4D5
      itself (Ka circa 6 nM). CONCLUSIONS: The RACK1 Interaction Domain on PDE4D5, that
      we here call RAID1, is proposed to form an amphipathic helical structure that we
      suggest may interact with the C-terminal beta-propeller blades of RACK1 in a
      manner akin to the interaction of the helical G-gamma signal transducing protein
      with the beta-propeller protein, G-beta.

PMID- 12193275
TI  - Identification of Ewing's sarcoma gene product as a glycoprotein using a
      monoclonal antibody that recognizes an immunodeterminant containing O-linked N
      acetylglucosamine moiety.
AB  - The Ewing's sarcoma (EWS) oncogene is fused to a variety of cellular
      transcription factors in various forms of human cancers. Although EWS fusion
      proteins have been extensively studied, the normal function of EWS remains poorly
      characterized. We previously reported that a monoclonal antibody, referred to as
      MY95, recognized nucleoporins such as p62, Nup98, and CAN/Nup214 and an
      uncharacterized polypeptide with an apparent molecular mass of 83 kDa. In the
      present study, an amino acid sequence analysis of this 83-kDa protein revealed
      that it is, in fact, EWS, which is not known to belong to the nucleoporins. We
      further demonstrated that the immunodeterminant of MY95 contains an N
      acetylglucosamine moiety, indicating that EWS is a glycoprotein. Interestingly,
      the glycosylation level of EWS changes during the neural differentiation of P19
      cells. MY95 will be quite useful in further studies of the glycosylated form of
      EWS in terms of understanding the normal cellular function of this oncogene
      product.

PMID- 12193276
TI  - In vivo expression of a GST-fusion protein mediates the rapid generation of
      affinity matured monoclonal antibodies using DNA-based immunizations.
AB  - Previously we demonstrated the rapid generation of affinity matured monoclonal
      antibody (MAb) producing cell lines following gene gun delivery of DNA using a
      mammalian expression vector (pAlpha/hFc), which enables the expression of human
      Fc-chimera proteins in vivo. Here we compare the pAlpha/hFc vector to modified
      vectors that replace human IgG(1) with either a Glutathione-S-Transferase (GST)
      fusion protein or a mouse IgG(2c) (mFc) fusion protein. We report that in vivo
      expression of a GST-chimera results in the rapid generation of affinity matured
      MAbs, comparable with antibodies raised using the pAlpha/hFc vector, that were
      reactive with annexin V. The mFc vector failed to induce early antigen-specific B
      cell responses suitable for MAb development.

PMID- 12193277
TI  - A panel of monoclonal antibodies against human polycomb group proteins.
AB  - Polycomb-group (PcG) proteins are chromatin-associated proteins that heritably
      repress gene activity in many organisms, including man. Two distinct human PcG
      complexes have been identified. The HPC/HPH PcG complex I contains the HPC, HPH,
      RING1, and BMI1 proteins, the EED/EZH2 PcG complex II contains the EED, EZH2, and
      YY1 proteins. Previously we found that the relative expression levels of proteins
      of the human PcG complexes I and II are severely deregulated in human tumors.
      These findings signify an important role for antibodies against human PcG
      proteins as diagnostic tools. To be able to produce standardized anti-human PcG
      antibodies, we developed a panel of five mouse monoclonal antibodies (MAbs)
      against the human PcG proteins HPC2, BMI1, RING1A, EED, and EZH2. All MAbs can be
      used for Western blot analysis and immunofluorescence labeling of tissue culture
      cells. With the exception of the MAb against HPC2, all MAbs can also be used in
      immunoprecipitation experiments and immunohistochemistry of human tissues. The
      novel MAbs are therefore valuable tools for the cell biological, biochemical, and
      pathological analysis of human PcG proteins.

PMID- 12193278
TI  - A novel monoclonal antibody recognizing a cation-dependent epitope within the
      regulatory loop of human beta(1) integrin (CD29).
AB  - Cell adhesion receptors of the integrin superfamily can be expressed in different
      affinity states towards their ligands. It has been previously demonstrated that
      beta(1) integrins alpha4beta(1) and alpha5beta(1) are expressed in a nonligand
      binding form by human hemopoietic progenitor cells but can be activated into a
      ligand binding form by a variety of stimuli including intracellular stimuli
      generated by cytokine receptors and extracellular stimuli generated by function
      activating anti-beta(1) integrin monoclonal antibodies (MAbs). In both instances,
      the activation of beta(1) integrins is believed to be the result of
      conformational changes propagating along the beta(1) integrin chain which in turn
      increase accessibility to the ligand. A cluster of either function-activating or
      function-inhibiting anti-beta(1) integrin MAbs have been shown to bind within a
      12 amino acid long regulatory loop between residues 207 and 218 of the human
      beta(1) integrin chain. We describe in this report the first MAb (96.9H9)
      specific for this regulatory loop whose binding is cation-dependent and requires
      either Ca(2+) or Mn(2+) but not Mg(2+). In addition, the activation of
      alpha4beta(1) and alpha5beta(1) integrins by 96.9H9 is a two-step process with
      distinct cation requirements. Whereas Ca(2+) is sufficient to promote binding of
      the antibody to the beta(1) integrin chain, Mg(2+) is necessary for activating
      function following 96.9H9 binding. Our data therefore suggest that the regulatory
      epitope of the human beta(1) integrin chain is flexible with multiple
      conformations according to the cationic environment.

PMID- 12193279
TI  - BRCA2 monoclonal antibodies react with differentiating epithelium.
AB  - The BRCA2 gene has previously been suggested to play a role in proliferation and
      DNA repair. Germline mutations in the BRCA2 gene predispose individuals to early
      onset, hereditary breast cancer. To better understand the expression pattern and
      function of the BRCA2 gene product, we have developed immunological reagents
      specific for BRCA2. These reagents recognize full-length (384 kDa) recombinant
      human BRCA2 proteins in transfected cell lysates as well as multiple smaller
      recombinant BRCA2 polypeptides. Detection of native BRCA2 protein in most tissue
      types, including breast epithelium, requires sensitive techniques such as
      immunoprecipitation-Western blot analysis. However, we have demonstrated strong
      reactivity of our immunological reagents with differentiating epithelium,
      including epidermis, thymic epithelium, and squamous cell carcinoma. These data
      suggest that BRCA2 may play a role in processes associated with cellular
      differentiation, in addition to its previously suggested roles in proliferation
      and DNA repair.

PMID- 12193280
TI  - Characterization of a monoclonal antibody specific for a novel primate cell
      surface marker with distinct biochemical properties on human erythroleukemia and
      myeloid cell lines.
AB  - A hybridoma, CSC-1, which secretes monoclonal antibody (MAb) specific for a cell
      surface molecule on African green monkey kidney cell line, BGMK, was isolated and
      characterized. The cell surface molecule recognized by CSC-1 is widely expressed
      on a variety of human cell lines. Among the hematopoietic cell lines examined,
      the CSC-1 marker seems to be preferentially expressed by lymphoid cell lines
      (e.g., Raji, CEM-SS, Jurkat, and MOLT-3). Although CSC-1 also recognizes some
      uncommitted myeloid and erythroleukemia cell lines (e.g., U-937 and K562), the
      CSC-1 marker expression on these cell lines is subjected to PMA-induced down
      regulation. In addition, the PMA-induced cell surface down-regulation of the CSC
      1 marker required more than 24 h. Proteolytic analysis shows that the CSC-1
      marker can be categorized into proteinase K-resistant and-sensitive phenotypes.
      Furthermore, the CSC-1 marker exhibits a slow cell surface turnover rate after
      proteinase K treatment. Our data suggest that the CSC-1 cell surface molecule
      might be useful as a megakaryocytic or monocytic differentiation marker.

PMID- 12193281
TI  - Monoclonal antibodies to gonadotropin-releasing hormone (GnRH) inhibit binding of
      the hormone to its receptor.
AB  - Monoclonal antibodies (MAbs) specific to gonadotropin-releasing hormone (GnRH)
      were obtained using different strategies of conjugation of the peptide to carrier
      protein and immunization. Of several antibodies obtained, two, namely F1D3C5 and
      E2D2 bound GnRH in solution phase. Though the epitopes corresponding to the two
      overlapped, there was a one amino acid shift in the core epitope. These two
      antibodies were characterized with respect to inhibition of GnRH induced
      responses in rat pituitary cultures and alpha-T3.1 mouse gonadotrope cell line.

PMID- 12193282
TI  - Production of antibodies by single DNA immunization: comparison of various
      immunization routes.
AB  - DNA immunization is a recent vaccination method that induces humoral and cellular
      immune responses in a range of hosts. Different immunization routes induce a
      different degree of the immune response. In the present report, we demonstrate
      that multiple intramuscular immunizations of plasmid DNA encoding various
      leukocyte surface molecules induced a specific antibody response. In contrast, a
      single intramuscular immunization could not induce antibody production. To study
      the induction of antibody response after a single immunization of plasmid DNA,
      mice were single-dose intramuscularly, intraperitoneally, intravenously and
      intrasplenically immunized, simultaneously, with the same preparation of plasmid
      DNA encoding CD147 membrane protein. We observed that only the intrasplenic route
      induced specific antibody production. The induction of antibody by intrasplenic
      immunization was confirmed by using plasmid DNA encoding CD54 molecule. By this
      single-dose DNA intrasplenic immunization, the generated antibodies could be
      detected in mice up to 6 months. These results suggest that the injected DNA is
      expressing the relevant protein antigen in the spleen for several months after
      injection. Our results demonstrate that direct immunization of antigen-encoding
      DNA into the spleen is a more effective method for induction of antibody
      production. This finding may support future investigations of DNA vaccination
      strategies that specifically promote the uptake of plasmid by splenocytes.
      Intrasplenic immunization may also be helpful in the understanding of the early
      events of the immune response to DNA vaccine and be useful as an effective route
      for the induction of immune responses.

PMID- 12193283
TI  - Development of a monoclonal antibody for neutralization of human telomerase
      activity.
AB  - To develop monoclonal antibodies (MAbs) to neutralize human telomerase, an
      epitope (hTERT(7)) in reverse transcriptase domain of hTERT was synthesized and
      was used to immunize BALB/c mice. Hybridomas were generated and screened by
      enzyme-linked immunoadsorbent assay (ELISA) for specific MAbs. One hybridoma M2
      clone, isotyped IgG(1), was established. The competitive assay confirmed that the
      M2 antibody was hTERT(7) specific, and the affinity constant was about 1 x 10(6)
      M(-1). M2 could recognize cell extracts from HeLa cancer cells but not those of
      normal 2BS cells in ELISA assay. For in situ staining immunohistochemically, the
      positive staining presented in the nuclear compartment of HeLa, while 2BS was
      nonreactive. In TRAP-PCR ELISA, M2 markedly decreased the activities of human
      telomerase in HeLa cells. The sequencing of M2 heavy chain variable region proved
      its mouse origin. The results demonstrated that the developed mouse MAb should be
      hTERT specific and could not only recognize native cellular hTERT in ELISA and
      immunohistochemistry, but also neutralize telomerase activities. Thus, it could
      be hoped that the antibody could be used in clinical diagnosis and treatment of
      cancers.

PMID- 12193284
TI  - Production of monoclonal and polyclonal antibodies against human
      alphafetoprotein, a hepatocellular tumor marker.
AB  - The objective of this study is to produce and purify monoclonal antibodies and
      polyclonal antibodies (PAbs) against human alphafetoprotein (AFP). Hyperimmune
      ICR mice produced PAbs after injection with 0.5 mL pristane, and were injected
      with NS-1 myeloma cells 2 weeks later. Hyperimmune Balb/c mice were used for the
      production of MAbs. Mice were immunized four times, given a final boost, and
      their spleen cells were collected and fused with NS-1 myeloma cells under the
      presence of PEG 1500. The fused cells were then selected in the hypoxanthine,
      aminopterine, and thymidine (HAT)-RPMIX medium. Anti-AFP antibody-secreting
      hybridoma cell lines with high titer were cloned by enzyme-linked immunosorbent
      assay (ELISA) and then subcloned by limiting dilution in 15% fetal bovine serum
      (FBS), hypoxanthine, thymidine (HT)-RPMIX medium. Twelve murine hybridoma
      producing anti-AFP MAbs were obtained and designated as A73F3, A73E8, B73C5,
      A73G3, A73F8, 67B3, B73C2, B73E1, A73G2, B73G7, B73D7, and B73F4. Isotypes of
      these MAbs were identified as IgG(1) heavy chain and kappa light chain. The MAbs
      with high purity were obtained by affinity chromatography. The purity analysis of
      AFP and the MAbs was performed by capillary electrophoresis.

PMID- 12193285
TI  - Specific monoclonal antibody against human trypsin.
AB  - A monoclonal antibody (MAb) directed against human trypsin-1 has been produced by
      hybridization of myeloma cells with spleen cells of BALB/c immunized mice.
      Antibodies were screened by ultramicro enzymelinked immunosorbent assay
      (UMELISA). MAb was purified by affinity chromatography on protein A-Sepharose,
      and MAb had a high affinity for trypsin-1 with the affinity constant equal 1.79 x
      10(9) L/mol. Specificity was studied by UMELISA using cross-reactant proteins;
      MAb gave a positive reaction with native trypsinogen-1 and with the same protein
      after reduction. Antibody appeared to be directed against sequential epitope. One
      step purification is described. The method evolved the adsorption of the enzyme
      onto a Sepharose-MAb(3H9) affinity column. The collected fraction was
      characterized and is available for immunization of BALB/c mice and for the
      preparation of a standard for immunoenzymatic assay.

PMID- 12193295
TI  - Choosing a career in thyroid.

PMID- 12193296
TI  - Isolation of a normal human thyroid cell line: hormonal requirement for
      thyroglobulin regulation.
AB  - The long-term culture of functional follicular cells from normal adult human
      thyroid tissue has been obtained. They were expanded using a 1:2 split ratio
      until passage 28 (present status) in Click-RPMI medium enhanced with 5% fetal
      calf serum and diverse associations of hormones or components including porcine
      insulin and bovine thyrotropin. At passages 10 and 20, chromosome countings
      showed a normal diploid number and a normal karyotype. In calf serum containing
      media, cells are epithelial in the presence of thyrotropin (TSH) but present a
      slight elongated form in the absence of TSH. In serum-free media, 30 minutes
      after TSH stimulation, both epithelial and elongated cells changed in morphology
      to stellate-shaped, arborized forms, indicating the presence of functional TSH
      receptors even in long term (18 months) TSH-free cultures. Cells produce
      thyroglobulin constitutively and large amounts of thyroglobulin are easily
      recovered in TSH-supplemented media, especially in the presence of insulin.
      Thyroglobulin production was increased versus days under TSH or insulin
      stimulation. Combination of the two hormones clearly resulted in a synergistic
      and not an additive effect. The other hormones present in the 6H components
      (transferrin, glycylhistidyl-lysine, somatostatin, and hydrocortisone) had no
      positive effect on thyroglobulin accumulation in media in our experimental
      conditions. Addition of TSH to hormone-free cultures or to insulin-, insulin plus
      hydrocortisone-, or 5H-containing cultures resulted in a clear increase in
      thyroglobulin production. Withdrawal of TSH from 6H cultures resulted in a
      decrease in thyroglobulin accumulation in media. Six months were required to
      select fibroblast-free cultures and to get passage 6. But only 17 months
      separated passage 6 to passage 28, indicating that the proliferative rate is
      increasing with in vitro cell adaptation. Such normal adult thyroid cells,
      thyroglobulin-producing, TSH, and insulin-sensitive, represent a new normal human
      thyroid cell line allowing comparative studies with cells originating from
      pathologic thyroid tissues.

PMID- 12193297
TI  - High-density lipoprotein-facilitated entry of thyroid hormones into cells: a
      mechanism different from the low-density lipoprotein-facilitated entry.
AB  - In human skin fibroblasts incubated with interstitial fluid concentrations of low
      density lipoproteins (LDL) (22 microg/mL) that had been preincubated with
      [(125)I] thyroid hormone (TH), thyroxine (T(4)) whole-cell saturable up-take
      (CSU) is approximately 40% greater than in control fibroblasts. This effect of
      the LDL, which requires upregulation of low-density lipoprotein-receptors (LDL-R;
      K(d) approximately 20 microg/mL), is less for [(125)I]triiodothyronine (T(3)). We
      have evaluated high-density lipoproteins (HDL), and assessed whether lipoproteins
      target TH to the nucleus. In some experiments, fibroblasts were cholesterol
      deprived (chol(-)) or cholesterol-enriched (chol(+)) to upregulate LDL-R or high
      density lipoprotein-receptors (HDL-R), respectively. In chol(-) fibroblasts, 25
      microg/mL of LDL increased both T(4) CSU and T(4) nuclear saturable uptake (NSU)
      by 48% or 30%, respectively; the latter becoming appreciable at approximately 180
      minutes. Interstitial fluid concentrations of HDL (280 microg/mL or approximately
      50-fold greater than K(d) of the HDL-R) inhibited both T(4) and T(3) CSU even in
      chol(+) fibroblasts. However, when chol(+) fibroblasts were incubated first with
      HDL, and after cell washings with [(125)I]T(4) or [(125)I]T(3), T(4) or T(3) CSU
      increased by 24% or 12%, respectively. The corresponding increase in chol(-)
      fibroblasts was 8% or 0%, and in nonmanipulated fibroblasts was 15% or 4%. Unlike
      LDL, the magnitude of the increase in T(4) or T(3) NSU caused by HDL matched the
      corresponding CSU, and was already evident at 30 minutes. In conclusion, cells
      have a LDL-facilitated, LDL-R-mediated mode of entry of TH (T(4) >> T(3)) that
      targets relatively late only part of TH to the nucleus, and an HDL-facilitated
      mode of entry (T(4) > T(3)) that targets immediately to the nucleus all of the
      TH, suggesting entry of TH in free form. This effect of HDL represents
      facilitated diffusion of TH through the cell membrane.

PMID- 12193298
TI  - Papillary thyroid carcinoma in patients with RET proto-oncogene germline
      mutation.
AB  - The occurrence of papillary thyroid carcinoma in patients with RET germline
      mutations has been described in only eight cases since 1993. We report three
      women with a RET germline mutation in exon 13 and 14, affecting codon 790, 791,
      and 804, respectively, who underwent prophylactic thyroidectomy at the age of 29,
      39, and 24 years, respectively. Histologic examination revealed C-cell
      hyperplasia and a small medullary thyroid carcinoma in the first patient and no
      pathologic changes of the C-cells in either of the other patients. However, all
      patients had papillary thyroid carcinoma (PTC). Concerning the frequency of PTC
      in patients with RET germline mutations who underwent surgery at our center (n =
      104), it was found in 9.1% of all patients with RET mutation in codon 790, 791,
      and 804 (n = 33) but in none of the 104 patients with RET germline mutations not
      affecting codon 790, 791, or 804 (p = 0.0015). Our data and the data from the
      literature suggest a possible pathogenesis of PTC caused by exon 13 and 14 RET
      mutations that affect the intracellular domain of the encoded protein. Further
      investigation is necessary to confirm a potential pathogenetic role of exon 13
      and 14 RET mutations with regard to the development of PTC.

PMID- 12193299
TI  - Cross-reactivity of a monoclonal antibody to the amino terminal region of
      thyrotropin receptor with the serum protein alpha(1)-antitrypsin.
AB  - In a study designed to detect the presence of soluble, secreted A subunit of
      thyrotropin hormone receptor (TSHR) in serum, using anti-TSHR murine antibodies
      (mAbs) and peptide specific antiserum for Western blotting of human serum
      proteins fractionated by sodium dodecyl sulfate-polyacrylamide gel
      electrophoresis (SDS-PAGE) it was consistently observed that only one mAb, termed
      A10, reacted strongly with the 53 kd serum protein. The reaction was specific
      with the mAb A10 only, but not with another mAb or polyclonal antiserum.
      Furthermore, A10 immunoreactivity was documented in a variety of sera from
      healthy donors and patients, including patients whose thyroid gland was ablated
      during treatment for thyroid cancer. This suggests that the A10 cross-reactive
      protein was not derived from thyroid cells. The A10 cross-reactive protein was
      purified from normal serum and subjected to N-terminal sequence analysis, which
      identified the protein as alpha(1)-antitrypsin. Further experiments by enzyme
      linked immunosorbent assay (ELISA) and the binding of antibody with
      deglycosylated or elastase-treated purified serum protein confirmed the cross
      reactivity of mAb A10 with alpha(1)-antitrypsin. Alignment of the TSHR amino acid
      sequence with that of alpha(1)-antitrypsin identified five identical amino acids
      in a short stretch of residues 34-39 (EEDFRV) in TSHR and residues 205-210
      (EEDFHV) in alpha(1)-antitrypsin. Analysis of the structural model of alpha(1)
      antitrypsin revealed that these residues were exposed on the surface of alpha(1)
      antitrypsin and were accessible for antibodies. Autoantibodies in patients with
      Graves' disease do not appear to recognize this region of the receptor and hence
      do not react with serum alpha(1)-antitrypsin.

PMID- 12193300
TI  - Feline thyroid adenomas are in part associated with mutations in the G(s alpha)
      gene and not with polymorphisms found in the thyrotropin receptor.
AB  - The etiopathogenesis of feline thyrotoxicosis is unknown. The transmembrane part
      (gene codons 480-640) of the thyrotropin receptor (TSHR) gene of hyperthyroid
      cats has already been investigated for the presence of stimulating mutations. No
      mutations were found in this part of the TSHR gene. We have investigated the TSHR
      gene codons 66-530 for gene mutations in 10 hyperthyroid cats and in 1 euthyroid
      cat. This part of the TSHR gene encodes the transmembrane part as well as most of
      the extracellular part of the receptor. The G(s alpha) gene of these cats was
      also sequenced and subjected to mutational analysis. Although our study revealed
      a polymorphism in the TSHR gene, no association was found with tumor formation.
      In 4 of 10 cats with hyperthyroidism a G(s alpha) gene mutation was found. This
      work suggests that mutations in the extracellular or transmembrane part of the
      TSHR gene are not likely the cause of feline hyperthyroidism. Mutations in the
      G(s alpha) gene, however, may play a role in the etiopathogenesis of this
      disease.

PMID- 12193301
TI  - Human immunodeficiency virus infection and the thyroid.
AB  - Abnormalities of thyroid function are associated with a number of systemic
      conditions, including patients infected with human immunodeficiency virus (HIV).
      Most patients with early HIV infection and a stable body weight have normal
      thyroid function. Subtle abnormalities of a number of thyroid function tests have
      been reported during the early asymptomatic phase of HIV disease. These include
      an inappropriately normal triiodothyronine (T(3)) and reduced reverse
      triiodothyronine (rT(3)), and increased thyroxine-binding globulin (TBG) levels.
      Opportunistic infections involving the thyroid gland, neoplasms such as lymphoma
      and Kaposi's sarcoma, and medications can alter the thyroid function in
      individuals with more advanced HIV infection. If thyroid dysfunction is diagnosed
      in an HIV-infected patient, it should be treated in the usual manner. However,
      high index of suspicion and caution in the interpretation of thyroid function
      tests in patients with HIV disease are needed for optimal diagnosis and
      treatment.

PMID- 12193302
TI  - Management of low-risk well-differentiated thyroid cancer based only on
      thyroglobulin measurement after recombinant human thyrotropin.
AB  - A multicenter study was undertaken to ascertain prevalence and significance of
      recombinant human thyrotropin (rhTSH)-stimulated increases in thyroglobulin (Tg)
      levels in thyroid cancer patients classified to be at low risk for recurrence.
      Patients were eligible for enrollment if they had undergone near-total or total
      thyroidectomy and remnant ablation between 1-10 years prior to enrollment and had
      received thyroxine suppression therapy (THST) with a TSH level of < 0.5 mU/L and
      Tg level less than or equal to 5 ng/mL within the prior year. Patients with anti
      Tg antibodies, distant metastases, or other evidence of residual disease were
      excluded. Four hundred eighty-six patients were entered into the study, and 300
      were considered eligible and comprise the study population. TSH, Tg, and anti-Tg
      antibody levels were obtained at baseline, followed by intramuscular injection of
      0.9 mg of rhTSH on days 1 and 2 and measurement of Tg on day 5. After rhTSH, 53
      patients (18%) had elevations in Tg of at least 2 ng/mL, including 33 patients
      (11%) with increases from baseline of equal to or greater than 5 ng/mL. Patients
      with an initial advanced stage of disease were more likely to display elevations
      in Tg after rhTSH. One third of those with stage III disease displayed elevations
      in Tg of 2 ng/mL or more. Patients within 5 years of thyroidectomy were as likely
      to display elevations in rhTSH-stimulated Tg as those 5-10 years from surgery. In
      conclusion, these data suggest rhTSH-stimulated Tg testing without scan may be a
      useful tool in the follow-up of patients with low-risk thyroid cancer, and may
      serve to identify patients previously thought free of disease on the basis of
      undetectable Tg levels while undergoing THST. A strategy is presented for
      incorporation of this approach into the management of patients with low-risk well
      differentiated thyroid cancer.

PMID- 12193304
TI  - Recombinant human TSH testing for recurrent thyroid cancer: a re-appraisal.

PMID- 12193303
TI  - A review of the case for neonatal thyrotropin screening in developing countries:
      the example of India.
AB  - BACKGROUND: Infantile hypothyroidism, either caused by iodine-deficiency disorder
      (IDD) or congenital hypothyroidism (CH), is the world's leading cause of
      preventable mental retardation. Such hypothyroidism has virtually been eliminated
      in the developed world by salt iodization and neonatal thyroid screening.
      However, most developing countries do not have neonatal thyroid screening
      programs. Using India as an example, we review the case for newborn screening in
      the developing world. METHODS: A literature review on infantile hypothyroidism in
      India was conducted and three Indian thyroid experts were queried about their
      views on neonatal screening in India. RESULTS: Iodine nutrition improved markedly
      in India during the 1990s; 49% of the households are now using adequately iodized
      salt. The control of IDD is still insufficient in India. Nationally
      representative data on neonatal screening in India are not available, but two
      regional studies have been published. One study (n = 12,407) measured cord blood
      thyrotropin and the other (n = 25,244) measured filter paper thyroxine. These
      studies reported difficult socioeconomic and organizational barriers to the
      implementation of neonatal screening in India. DISCUSSION: It is time for India
      to make neonatal thyroid screening and mandatory iodization of salt a priority
      and develop a comprehensive infantile hypothyroidism policy. Prioritization of
      infantile hypothyroidism prevention is justified by its high frequency,
      sensitivity of screening in detecting both IDD and CH, adverse consequences of
      missing diagnosis at birth, high effectiveness of prevention, severity of
      disability from hypothyroidism, cost effectiveness of prevention, and lack of a
      clinical method of diagnosis near birth.

PMID- 12193305
TI  - Orbital gallium-67 scintigraphy in Graves' ophthalmopathy.
AB  - Assessment of orbital disease activity in patients with Graves' ophthalmopathy is
      important in planning the therapeutic approach. In this study, orbital uptake of
      gallium-67 citrate ((67)Ga) was evaluated in 46 consecutive patients
      demonstrating active or inactive Graves' ophthalmopathy. The disease activity
      with Graves' ophthalmopathy was evaluated by using clinical activity score (CAS).
      Orbital (67)Ga scintigraphies of 8 patients without any history of ophthalmic,
      thyroid, or autoimmune disease were studied as controls. (67)Ga scintigraphy was
      performed 48 hours after intravenous injection of 4 mCi (128 MBq) of radioactive
      complex. Single-photon emission computed tomography (SPECT) images were obtained
      with a gamma camera. Intravenous corticosteroid treatment was given to 8 selected
      patients demonstrating bilateral active orbital disease and (67)Ga scintigraphy
      was repeated 6 months after the treatment. Quantitative analysis of mean orbital
      (67)Ga uptake demonstrated significant difference between active, inactive, and
      control groups (p = 0.0001). The orbital uptake of (67)Ga was significantly
      elevated in the active group compared to the inactive and control groups. A
      threshold orbital (67)Ga uptake value was calculated to differentiate active and
      inactive groups based on receiver operating characteristic (ROC) analysis. A
      significant correlation was found between the CAS and the (67)Ga orbital uptake
      (r = 0.73, p = 0.0001). Clinical improvement and significant decrease in orbital
      (67)Ga uptake were achieved after immunosuppressive treatment (p = 0.0004). These
      preliminary results suggest that orbital (67)Ga scintigraphy may provide
      objective assessment of the disease activity in Graves' ophthalmopathy.

PMID- 12193306
TI  - Thyroid peroxidase antibodies in dried blood specimens of newborns.
AB  - Previous studies have disclosed that a substantial percentage of infants from
      mothers with thyroid autoimmunity have antibodies to thyroid peroxidase (TPOAb)
      at birth. Furthermore, these antibodies have been shown to be of maternal origin.
      In view of this we thought it would be of interest to determine the prevalence of
      TPOAb in newborns from an unselected population of women. This was done by
      retrieving stored dried blood specimens from 240 full-term healthy infants, which
      had been obtained during 1999 for routine newborn screening. Ten percent of the
      randomly selected specimens tested TPOAb positive. Thyroid function in the
      mothers could not be evaluated because all specimens had been tested anonymously.
      In summary, our results indicate that a significant percentage of newborns were
      TPOAb positive. It is unclear at this time whether such antibodies reflected
      maternal thyroid autoimmunity and/or other autoimmune disorders. However, the
      close association between autoimmune thyroid disease and TPOAb positivity raises
      the possibility of abnormal thyroid function in some of the mothers.

PMID- 12193308
TI  - The accuracy of fine-needle aspiration biopsy and frozen section in patients with
      thyroid cancer.
AB  - A total of 1076 patients with thyroid nodules were reviewed. The accuracy of fine
      needle aspiration biopsy (FNAB) and frozen section (FS) were compared and
      clinical risk factors were analyzed. Our results indicate that 67.9% are benign
      and 32.1% are malignant with the predominance of papillary thyroid cancer
      (75.1%). Overall diagnostic accuracy for FNAB and FS were 90.8%-91.2% and 89.1%
      90.5%, respectively. There were no significant differences between the diagnostic
      accuracy on FNAB and FS in all tumors except the follicular adenoma and
      carcinoma. The diagnostic accuracy of FS was higher than FNAB in patients with
      follicular adenoma (89.3% vs. 58.9%, p < 0.001) and but lower than FNAB in
      patients with follicular carcinoma (46.2% vs. 92.3%, p < 0.001). In conclusion,
      FNAB is cost effective in the preoperative evaluation of thyroid nodule. FS could
      be eliminated in most cases except with follicular and Hurthle cell neoplasms. FS
      is valuable when result of FNAB is suspicious or unavailable. FS is more
      appropriate in deciding the extent of thyroidectomy in follicular neoplasm and
      FNAB is more reliable initial approach to surgery in patients with Hurthle cell
      neoplasm. Clinical risk factors may help in selecting patients for surgery but
      cannot exceed FS in deciding the extent of thyroidectomy in patients with
      follicular and Hurthle cell neoplasms.

PMID- 12193307
TI  - Relationship between thyroid autoimmunity and Yersinia enterocolitica antibodies.
AB  - It has previously been proposed that subclinical Yersinia enterocolitica
      infection may play a role in autoimmune thyroid disease (AITD). In this study, we
      investigated the relationship between the thyroid autoantibodies and the
      antibodies that produced against different serotypes of Y. enterocolitica. A
      total of 215 subjects were included into the study (65 newly diagnosed Graves'
      disease [GD], 57 Hashimoto's thyroiditis [HT], 53 nontoxic diffuse goiter [NTDG],
      and 40 subjects for control group [CG]). Thyroid receptor antibodies (TRAb),
      thyroid and agglutinating antibodies against Y. enterocolitica serotype O:3, O:5,
      O:8, O:9 were measured in the blood samples. The highest incidence of Y.
      enterocolitica antibody positivity was measured in GD (53.8% for O:3, 29.2% for
      O:5, 44.6% for O:8, and 40% for O:9) and followed by HT. In patients with GD,
      TRAb levels were also higher than in patients with HT, NTDG, and CG. There was no
      difference between NTDG and CG in respect to the titer levels and the positivity
      of both TRAb and Y. enterocolitica antibodies. There was also a weak linear
      correlation between TRAb level and the titer of antibodies against Y.
      enterocolitica antigens. It can be concluded that Y. enterocolitica infection may
      play a role in etiology of GD in Turkey.

PMID- 12193310
TI  - Gluten-induced enteropathy (coeliac disease) revealed by resistance to treatment
      with levothyroxine and alfacalcidol in a sixty-eight-year-old patient: a case
      report.
AB  - We report the case of a female patient in whom gluten-induced enteropathy was
      revealed at the age of 68 years by resistance to treatment with levothyroxine and
      alfacalcidol. This case report shows that malabsorption without major digestive
      symptoms led to reduction of absorption of levothyroxine (LT(4)) and
      alfacalcidol, although the patient had normal free thyroxine (T(4)) levels (which
      increased by 45.8% after a loading dose of 250 microg of levothyroxine), high
      thyrotropin (TSH) and slightly elevated 1.25 dihydroxy-vitamin D(3) levels, low
      free triiodothyronine (T(3)) and calcium levels were found. Malabsorption had
      additional effects by reducing T(3) and calcium levels. Because minor forms of
      gluten-induced enteropathy are not rare in patients with thyroid autoimmune
      diseases, the cost-effectiveness of using antigliadin antibodies as a first-line
      test (instead of an LT(4) loading test) in patients requiring daily doses of
      levothyroxine above 2 microg per kg of body weight, whatever their age may be, is
      discussed.

PMID- 12193309
TI  - Rectal administration of propylthiouracil in hyperthyroid patients: comparison of
      suspension enema and suppository form.
AB  - Previous studies have described the therapeutic effects of propylthiouracil (PTU)
      and methimazole in normal subjects after rectal suppositories. The goal of our
      study was to compare the pharmacokinetic and pharmacologic effects of a
      suppository and suspension form of PTU given per rectum. Fifteen newly diagnosed
      hyperthyroid patients of both genders (ages 21 to 55 years) were randomly given
      the drug as follows: group 1 (n = 7), a single enema (400 mg of PTU in 90 mL of
      sterile water) and group 2 (n = 8), two suppositories of polyethylene glycol base
      (200 mg of PTU in each). The pharmacokinetic study revealed earlier time to peak
      levels (T(max)) and significantly greater maximal peak levels (C(max)) in group 1
      than in group 2, (85.71 +/- 12.12 minutes vs. 172.5 +/- 26.24 minutes for T(max)
      and 3.89 +/- 0.34 vs. 2.01 +/- 0.38 microg/mL, p < 0.05 for C(max),
      respectively). However, the area under the curve (635.16 +/- 105.71 vs. 377.87 +/
      68.09 microg x min/mL) was not statistically different between both groups. Both
      forms induced a significant decrease in serum free triiodothyronine (FT(3))
      levels and an increase in serum rT(3) levels shortly after administration. Four
      subjects reported a bitter taste 5-10 minutes after receiving the drug. PTU can
      be effectively absorbed via the rectal route. The enema form appeared to provide
      better bioavailability than the suppository form. However, both preparations
      exhibited comparable therapeutic effect.

PMID- 12193312
TI  - A serpentine thyroid.

PMID- 12193311
TI  - Massive triiodothyronine intoxication: efficacy of hemoperfusion?
AB  - A case of massive accidental triiodothyronine intoxication (1000-fold the usual
      therapeutic dose, for 8 days) is reported with important disturbances of
      cardiovascular and central nervous systems that required intensive care support.
      Serum free triiodothyronine levels were 4789 pmol L(-1) on admittance (normal
      values, 3.5-6.5 pmol x L(-1)). In the absence of a specific treatment,
      hemoperfusions were performed but failed to accelerate significantly the decay of
      blood levels of free triiodothyronine (apparent half-life 25.9 hours; 95%
      confidence interval: 19.8-37.4 hours). The patient, a young woman, made a
      satisfactory recovery, in spite of important clinical complications.

PMID- 12193314
TI  - Medical education terminology.

PMID- 12193315
TI  - Twelve tips for undertaking a systematic review.
AB  - The need to underpin health and education with a firm evidence base is of
      increasing significance. Systematic review offers an effective approach to
      critically assessing research in order to understand its overall impact on
      practice. Based on 5 years' experience undertaking systematic reviews of
      interprofessional education, this paper offers guidance for researchers and
      practitioners about to embark upon systematic review work.

PMID- 12193316
TI  - Developing the teaching instinct, 2: supervision.

PMID- 12193317
TI  - New edition of Tomorrow's Doctors.
AB  - The GMC's publication, Tomorrow's Doctors, sets out the framework for
      undergraduate medical education in the UK. The original version was published in
      1993, and had a profound effect on encouraging UK medical schools to develop new
      and innovative curricula. The GMC has now revised this guidance to take account
      of developments in educational theory and research since 1993; and to address
      issues identified during two rounds of visits to all UK medical schools to
      monitor the implementation of its guidance between 1995 and 2001. The revised
      document places the principles of professional practice at the heart of
      undergraduate medical education, and identifies the outcomes required of all
      medical graduates.

PMID- 12193318
TI  - Assessment of empathy in different years of internal medicine training.
AB  - The operational measurement of physician empathy, as well as the question of
      whether empathy could change at different levels of medical education, is of
      interest to medical educators. To address this issue, 98 internal medicine
      residents from all 3 years of training were studied. The Jefferson Scale of
      Physician Empathy was administered, and residents' empathy scores correlated with
      ratings on humanistic attributes made by postgraduate program directors. No
      statistically significant differences in scores were found among residents of
      different training levels. Empathy scores remained also stable during internship
      (test-retest reliability = 0.72). Correlation between empathy and ratings on
      humanism was 0.17. Thus, the findings suggest that empathy is a relatively stable
      trait that is not easily amenable to change in residency training programs. The
      issue of whether targeted educational activities for the purpose of cultivating
      empathy can improve empathy scores awaits empirical scrutiny.

PMID- 12193319
TI  - Altruism and compassion in the health professions: a search for clarity and
      precision.
AB  - This article presents a conceptual model of altruism grounded in compassion in
      the health professions. The intent is to bring order out of the current
      conceptual chaos about the meaning and practical operation of these constructs.
      The theory-based model proposes that altruism is expressed as overt behavior in
      specific situations that vary in levels of intensity. It assumes that altruism is
      not a broad-based, cross-situational personal trait; that altruism can be
      measured objectively; and that altruism can be increased via education, practice
      and reinforcement. The article concludes by demonstrating the progression from
      formation of a theory-based conceptual model, development of objective measures,
      performing systematic research and accumulating an orderly and consensual body of
      knowledge about altruism grounded in compassion in the health professions.

PMID- 12193320
TI  - Illuminating the relationship between shared learning and the workplace.
AB  - This investigation represents an attempt to illuminate issues in the relationship
      between shared learning, aspects of organizational climate, teamwork practices
      and inter-personal contact between health professionals. The study, completed in
      1998 and conducted over the previous 3 years, involved 57 post-qualified health
      professionals undertaking a part-time 'top-up' degree in health studies. The
      extent to which climate promoted, maintained or inhibited collaborative practices
      was considered by examining the views and experiences of course participants over
      three successive years. Most interest in collaborative practice came from
      individuals already actively engaged in multidisciplinary work and with a clear
      sense of role within that context. No evidence was found to associate this form
      of shared learning with new or enhanced collaborative activity, but nearly all
      the professions involved accepted the principle of more flexible forms of
      working. Poor perceptions between disciplines were associated with low levels of
      contact in the workplace. Students who undertook a module focusing on
      collaborative practice had more positive perceptions about their work and were
      less likely to emphasize work demands in terms of shift-patterns, fatigue and/or
      stress.

PMID- 12193321
TI  - A framework for effective training for supervisors.
AB  - The purpose of this paper is to identify the key theoretical and empirical
      considerations that should underpin effective training for supervisors. Decisions
      about the content of training courses are complex because there is no appropriate
      model of supervision in medicine. This paper argues that, in the absence of an
      explanatory model, effective training for supervisors should be based on existing
      relevant understandings about learning processes and models of supervision,
      together with relevant empirical data. It explores some useful models of
      supervision, considers helpful aspects of theories about learning from experience
      and identifies some relevant empirical findings to identify some key theoretical
      and empirical considerations that should underpin effective training for
      supervisors. This paper offers a framework, derived from both empirical and
      theoretical work, to guide the content of effective supervision training courses.
      It does not prescribe structure or organization of training but suggests a basis
      for devising specific courses for response to local needs.

PMID- 12193322
TI  - Are extended-matching multiple-choice items appropriate for a final test in
      medical education?
AB  - At the Faculty of Medicine of the KU Leuven a 'final' test is being developed,
      part of which consists of extended matching multiple-choice questions (EMQs).
      These are problem-oriented questions referring to a realistic case, with the
      correct answer to be chosen from a list of 7-26 possible answers. The same list
      can be used for several questions (cases). Staff members of 10 medical
      specialties have developed about 900 questions. In order to test the quality of
      these questions, they were submitted in series of 100 questions to 251 final-year
      students who were not specifically prepared for content, or for question format.
      The organization of the test ran without problems. It was possible to answer 100
      EMQs within half a day (i.e. 4 hours). Fatigue had no measurable influence on the
      score over this period but increasing familiarity with the question format was
      observed. In order to obtain a reliable series of questions those questions that
      correlated negatively with the total score were deleted until a Cronbach alpha of
      0.80 was reached. Split-half reliability coefficients were of the same order of
      magnitude. The score on a questionnaire concerning the perception of the test
      indicated poor face validity. The procedure of test construction gave arguments
      for content validity. The correlation between test score and total examination
      score of each of the 7 years of medical education was statistically significant,
      which indicates criterion validity. Therefore, starting from 100 EMQs per student
      it was possible to develop a reliable and valid test. EMQs seem to be appropriate
      for a final test of clinical knowledge in medical education.

PMID- 12193323
TI  - Advantages of using the multiple case method at the clinical stage of medical
      education.
AB  - The multiple case method is an uncomplicated form of discussion learning. Its
      primary objective is to make students familiar with knowledge already presented
      to them in lectures and written material. For each session, a large number of
      situations within a theme are described in handouts. After individual preparatory
      work, a group of 20-40 (-60) students cooperates to reach understanding and
      acceptable handling. The main tasks of the teacher are to stimulate the
      discussion and detect misunderstandings. In a course on infectious diseases, we
      have successfully used this method of teaching on a large scale for more than a
      decade. During 24 consecutive runs of the course, with a total of approximately
      500 students over a 6-year period, the method was consistently rated high by the
      students. The long-term persistence of this method can be attributed not only to
      its learning value but also to the fact that it is simple and easy to practise
      with relatively large groups of students, thereby decreasing the risk of
      teachers' burnout.

PMID- 12193324
TI  - Medical students' experiences of diseases in internal medicine in university and
      community hospitals.
AB  - Because medical students in The Netherlands should achieve common national
      objectives, it is important to know whether clinical experiences in different
      hospitals are comparable. The research questions were: (1) Do students achieve
      learning experiences of the required diseases during the internship in Internal
      Medicine and to what extent do they achieve these experiences? (2) Are there
      differences between the diseases experienced at a university hospital and at
      community hospitals? Completed logbooks of students were analysed; the percentage
      of students that achieved the required diseases and the mean number of
      experiences of diseases were calculated. A t-test was done to test for
      differences. Medical students in the university and in community hospitals get
      broad experience (76-131%) of the required diseases. In both hospitals there are
      many students who are not achieving the requirements, but the mean number of
      experiences of students at the community hospitals is higher than those at the
      university hospital. To eliminate the differences between students from the
      university hospital and the community hospitals, the educational programmes
      within both hospitals should be adjusted.

PMID- 12193325
TI  - Peer consultation as a method for promoting problem-based learning during a
      paediatrics course.
AB  - In problem-based learning (PBL) there are problems during tutorial group
      sessions, for example lack of participation, interaction and cohesion, and
      withdrawing. The authors evaluated whether these problems could be avoided with a
      peer consultation model. Peer consultation takes advantage of cooperation between
      students by encouraging them to accept more responsibility for learning from
      their peers. Forty-nine fifth-year students participated in three group sessions
      where they solved a paediatric case problem. The students were working in small
      groups, assuming the following roles in turn: presenters, facilitators and
      observers. The students reported that this consultative method forced one to
      actually define the problem, helped to develop communication skills and to
      identify problematic issues from different viewpoints and offered the possibility
      to evaluate personal problem-solving strategies. The method also gave an
      opportunity for students to learn in practice how to utilize new technology in
      data searching. These experiences suggest that the model of peer consultation
      adds new flavour, increasing enthusiasm in problem-based learning.

PMID- 12193326
TI  - Development and evaluation of a computer-assisted learning module on
      glomerulonephritis for medical students.
AB  - An interactive computer-assisted learning (CAL) module on glomerulonephritis,
      previously identified by fourth-year medical students as a difficult topic, was
      developed. The module comprised background material, case studies, graphics,
      animation, video and supporting quizzes with feedback. The impact of the module
      on student learning was evaluated by comparing the performance of two matched
      groups of students, only one of which accessed the CAL module, in an online
      assessment. The analysis examined the effect of having completed a clinical term
      in renal medicine. A significant improvement in the performance of those students
      who used the CAL module was demonstrated. Unexpectedly, completing a renal
      medicine term had no beneficial influence on students' performance. Students who
      used the CAL module perceived a significant decrease in the difficulty of the
      topic. It is concluded that the module is an effective learning tool, but
      important caveats are noted associated with using CAL modules in redesigned
      medical curricula.

PMID- 12193327
TI  - 'Ten golden rules' for designing software in medical education: results from a
      formative evaluation of DIALOG.
AB  - Evaluation of educational material has become very important in a climate where
      there is increasing concern with assessing and maintaining quality. DIALOG
      (acronym for Distance Interactive Learning in Obstetrics and Gynaecology) is an
      electronic program on CD-ROM for continuing education. A formative evaluation of
      DIALOG was carried out to determine whether DIALOG was achieving its educational
      objectives. The results of the evaluation helped to suggest '10 golden rules' for
      designing software for the purpose of CPD for medical practitioners. These
      'rules' should help in designing future software in medical education. They
      highlight the importance of content, presentation, design, use of hypermedia and
      multimedia and reduced cost in order to facilitate appropriate use of such
      programmes.

PMID- 12193328
TI  - Medical teaching websites: do they reflect the learning paradigm?
AB  - Phenomenal evolution of the Internet in recent times is shifting the mode of
      distribution of medical knowledge from conventional lecture rooms to one that is
      web based. No guidelines are yet set for medical teaching websites. Hence, the
      authors set out to determine whether these sites uniformly reflected the Learning
      Paradigm. Most of the medical teaching websites were endowed with good technical
      support but were surprisingly falling short in reflecting the principles of
      learning. It is strongly suggested that a team consisting of a clinician as
      content provider, a web designer and a medical educationist is required to create
      an ideal medical teaching website.

PMID- 12193329
TI  - Student access and use of IT during general practice attachments.
AB  - As universities change the delivery of their medical undergraduate courses, many
      have started to develop the community as a learning resource. In Manchester, part
      of the rationale behind problem-based learning is that students become familiar
      with the tools for finding information. Within the medical school and its main
      teaching hospitals, students have access to varied information resources using
      IT. These are often less available from off-campus sites and particularly within
      general practice. Even where available, students may not use them. Initial
      evaluation suggests that IT facilities are particularly useful for students who
      have longer placements. However, students prioritize their use of time in the
      community and furnishing general practices with a computer and other IT equipment
      does not, in itself, promote use by the students unless there is a perceived
      need. Training and support within the practice needs to be undertaken to enhance
      the learning environment for the undergraduates.

PMID- 12193330
TI  - Teaching by hospitalist physicians: a practical approach.
AB  - This article discusses an approach to the teaching of residents and medical
      students by hospitalist physicians on a general pediatric unit. It focuses on
      three basic principles of teaching and describes how these can be operationalized
      in a practical way. If this approach is followed, hospitalist physicians can be
      more effective teachers.

PMID- 12193331
TI  - Information-sharing strategies to support practising clinicians in their clinical
      teaching roles.
AB  - If the involvement of practising clinicians in undergraduate clinical teaching is
      to be retained, strategies that inform them of student expectations and show how
      their contribution can be integrated to the wider clinical teaching programme
      must be identified. A variety of information-sharing strategies has been designed
      and used to communicate with clinicians teaching in Phase 2 of the undergraduate
      medical curriculum in Dundee. Evaluation of these by the clinical teaching staff
      has indicated that briefing by students, posters and tutor manuals are more
      successful information-sharing strategies than formal staff-development sessions.

PMID- 12193332
TI  - South Cheshire Local Multi-disciplinary Evidence Centre: an evaluation.
AB  - The South Cheshire Local Multidisciplinary Evidence Centre (LMEC) was a two-year
      project commenced in March 1998 and completed in April 2000. The project aimed to
      develop an information service to enable all primary and community care staff in
      South Cheshire to access high-quality evidence and thus to improve patient care.
      The LMEC gave access from the workplace to both physical and electronic resources
      to support clinical governance and lifelong learning, with a strong emphasis on
      evidence-based material. Automation of the library catalogue enabled its
      inclusion on the website. The project developed enquiry and document delivery
      services and provided training on using the LMEC and on critical appraisal. An
      evaluation carried out at the end of the project showed that over 120 primary and
      community care staff had used the LMEC and were positive about the service. As
      Clinical Governance, the NHSnet, and plans for continuing professional
      development are implemented, the LMEC is one model for a Local Health Information
      Service outlined in the NHS IT strategy.

PMID- 12193333
TI  - Teaching EBM facilitation using small groups.
AB  - The problem-centered, learner-focused, small-group process (PLS) is used by
      faculty to train learners in evidence-based medicine (EBM). Few affordable and
      accessible courses exist to train faculty in the PLS process. The results of a
      novel course to train faculty in the PLS process are described. The course was a
      one-day workshop consisting of five small group sessions with two facilitators.
      The participants were seven clinicians and four medical librarians. The initial
      small-group session was a discussion of concepts and principles related to
      successful facilitation skills; the subsequent four small groups reinforced these
      concepts and principles with role-playing and case scenarios using different
      steps in the EBM process. The course, including the use of the PLS process,
      scored highly on participant evaluations. The authors conclude that the
      introductory course effectively taught the PLS process for use in EBM
      facilitation.

PMID- 12193334
TI  - Implementation of a cross-cultural evidence-based medicine curriculum.
AB  - While principles of evidence-based medicine (EBM) are increasingly prevalent in
      medical education curricula in Europe and North America, medical educators
      elsewhere face formidable barriers to its implementation. We sought to determine
      the feasibility of implementing a learner-centered, case-based EBM curriculum
      among academic physicians in Kazan, Russia, facilitated by residents
      participating in an international health elective. This article reports that
      implementation of an EBM curriculum is feasible during a resident international
      health elective and that mutually beneficial educational exchanges represent an
      opportunity for teaching the tenets of EBM abroad.

PMID- 12193335
TI  - New vision of medical education is not based on evidence.

PMID- 12193336
TI  - OSCE means 'Scotland' in French.

PMID- 12193337
TI  - Glossary of medical education terms: part 3.

PMID- 12193339
TI  - World summit on sustainable development.

PMID- 12193340
TI  - Making blood safer.

PMID- 12193341
TI  - Child labour.

PMID- 12193343
TI  - Surgeons cleared of serious professional misconduct by GMC.

PMID- 12193342
TI  - Targeting people with pre-diabetes.

PMID- 12193344
TI  - Health, poverty, and sanitation to feature highly in world summit.

PMID- 12193345
TI  - Health authorities on alert after extensive flooding in Europe.

PMID- 12193346
TI  - Medical agency suspends aid in Dagestan after kidnapping.

PMID- 12193347
TI  - NICE proposals for citizens council condemned by patients. National Institute for
      Clinical Excellence.

PMID- 12193349
TI  - Junior consultants will leave BMA "hand over fist," warns chairman.

PMID- 12193350
TI  - Clinical negligence lawyers told to improve their performance.

PMID- 12193353
TI  - Local warming and insertion of peripheral venous cannulas: single blinded
      prospective randomised controlled trial and single blinded randomised crossover
      trial.
AB  - OBJECTIVE: To determine whether local warming of the lower arm and hand
      facilitates peripheral venous cannulation. DESIGN: Single blinded prospective
      randomised controlled trial and single blinded randomised crossover trial.
      SETTING: Neurosurgical unit and haematology ward of university hospital.
      PARTICIPANTS: 100 neurosurgical patients and 40 patients with leukaemia who
      required chemotherapy. INTERVENTIONS: Neurosurgical patients' hands and forearms
      were covered for 15 minutes with a carbon fibre heating mitt. Patients were
      assigned randomly to active warming at 52 degrees C or passive insulation (heater
      not activated). The same warming system was used for 10 minutes in patients with
      leukaemia. They were assigned randomly to active warming or passive insulation on
      day 1 and given alternative treatment during the subsequent visit. MAIN OUTCOME
      MEASURES: PRIMARY: success rate for insertion of 18 gauge cannula into vein on
      back of hand. SECONDARY: time required for successful cannulation. RESULTS: In
      neurosurgical patients, it took 36 seconds (95% confidence interval 31 to 40
      seconds) to insert a cannula in the active warming group and 62 (50 to 74)
      seconds in the passive insulation group (P=0.002). Three (6%) first attempts
      failed in the active warming group compared with 14 (28%) in the passive
      insulation group (P=0.008). The crossover study in patients with leukaemia showed
      that insertion time was reduced by 20 seconds (8 to 32, P=0.013) with active
      warming and that failure rates at first attempt were 6% with warming and 30% with
      passive insulation (P<0.001). CONCLUSIONS: Local warming facilitates the
      insertion of peripheral venous cannulas, reducing both time and number of
      attempts required. This may decrease the time staff spend inserting cannulas,
      reduce supply costs, and improve patient satisfaction.

PMID- 12193355
TI  - Skin prick testing.

PMID- 12193354
TI  - Sensitisation to airborne moulds and severity of asthma: cross sectional study
      from European Community respiratory health survey.
AB  - OBJECTIVE: To assess whether the severity of asthma is associated with
      sensitisation to airborne moulds rather than to other seasonal or perennial
      allergens. DESIGN: Multicentre epidemiological survey in 30 centres. SETTING:
      European Community respiratory health survey. PARTICIPANTS: 1132 adults aged 20
      44 years with current asthma and with skin prick test results. MAIN OUTCOME
      MEASURES: Severity of asthma according to score based on forced expiratory volume
      in one second, number of asthma attacks, hospital admissions for breathing
      problems, and use of corticosteroids in past 12 months. RESULTS: The frequency of
      sensitisation to moulds (Alternaria alternata or Cladosporium herbarum, or both)
      increased significantly with increasing asthma severity (odds ratio 2.34 (95%
      confidence interval 1.56 to 3.52) for either for severe v mild asthma). This
      association existed in all of the study areas (gathered into regions), although
      there were differences in the frequency of sensitisation. There was no
      association between asthma severity and sensitisation to pollens or cats.
      Sensitisation to Dermatophagoides pteronyssinus was also positively associated
      with severity. In multivariable logistic regressions including sensitisation to
      moulds, pollens, D pteronyssinus, and cats simultaneously, the odds ratios for
      sensitisation to moulds were 1.48 (0.97 to 2.26) for moderate v mild asthma and
      2.16 (1.37 to 3.35) for severe v mild asthma (P<0.001 for trend). CONCLUSIONS:
      Sensitisation to moulds is a powerful risk factor for severe asthma in adults.
      This should be taken into account in primary prevention, management, and
      patients' education.

PMID- 12193356
TI  - Thrombolysis for acute ischaemic stroke: consumer involvement in design of new
      randomised controlled trial.
AB  - OBJECTIVES: To determine whether consumer involvement would help to solve some of
      the ethical problems associated with research into thrombolysis for acute
      ischaemic stroke, with its inherent risk of fatal intracranial haemorrhage.
      DESIGN: Quantitative and qualitative research. SETTING AND PARTICIPANTS:
      CONSULTATION PHASE: three meetings were held to discuss the planned research, and
      participants completed a questionnaire. QUALITATIVE WORK: focus group meetings
      explored the issues raised during the consultation phase. Design of information
      leaflets for patients and relatives: trial materials were drafted during the
      consultation phase and revised in the light of feedback from the focus group
      meetings and review by patients and carers on a stroke rehabilitation unit.
      RESULTS: 54 people attended the consultation meetings. Four (9%) participants
      considered the risks of thrombolysis too great, but most (89%) were prepared to
      accept the treatment in a clinical trial. Nearly all would accept treatment if it
      was shown to be effective. Most (85%) would give their consent to enter the
      planned trial. The focus group meetings and feedback from patients and carers led
      to significant changes in the information leaflets. The revised trial materials
      were considered ethical by a national multicentre research ethics committee.
      CONCLUSIONS: Consumers generally supported a planned trial, and their involvement
      helped to refine trial consent procedures and led to an ethically acceptable
      trial design.

PMID- 12193357
TI  - Are breast cancer screening programmes increasing rates of mastectomy?
      Observational study.

PMID- 12193358
TI  - Relation of childhood gastrointestinal disorders to autism: nested case-control
      study using data from the UK General Practice Research Database.
AB  - OBJECTIVES: To assess whether children with autism are more likely to have a
      history of gastrointestinal disorders than children without autism. DESIGN:
      Nested case-control study. SETTING: UK General Practice Research Database.
      SUBJECTS: Children born after 1 January 1988 and registered with the General
      Practice Research Database within 6 months of birth. OUTCOME MEASURES: Chronic
      inflammation of the gastrointestinal tract, coeliac disease, food intolerance,
      and recurrent gastrointestinal symptoms recorded by the general practitioner.
      RESULTS: 9 of 96 (9%) children with a diagnosis of autism (cases) and 41 of 449
      (9%) children without autism (matched controls) had a history of gastrointestinal
      disorders before the index date (the date of first recorded diagnosis of autism
      in the cases and the same date for controls). The estimated odds ratio for a
      history of gastrointestinal disorders among children with autism compared with
      children without autism was 1.0 (95% confidence interval 0.5 to 2.2).
      CONCLUSIONS: No evidence was found that children with autism were more likely
      than children without autism to have had defined gastrointestinal disorders at
      any time before their diagnosis of autism.

PMID- 12193359
TI  - Management of chronic heart failure.

PMID- 12193360
TI  - Trauma.

PMID- 12193361
TI  - Anti-vaccinationists past and present.

PMID- 12193362
TI  - Working with the private sector: the need for institutional guidelines.

PMID- 12193363
TI  - "Food deserts"--evidence and assumption in health policy making.

PMID- 12193364
TI  - Preventing stroke with ramipril. Results should have been presented in ways that
      help practising clinicians.

PMID- 12193365
TI  - New trial should clarify lithium use in bipolar disorder.

PMID- 12193366
TI  - Burden of illness and suicide in elderly people. Physical disease and depression
      are prevalent in elderly Finnish suicide victims.

PMID- 12193367
TI  - Negotiators explain flexible training under the new deal.

PMID- 12193368
TI  - Interpreting exercise treadmill tests needs scoring system.

PMID- 12193369
TI  - Authors respond to criticisms of booked inpatient admissions and hospital
      capacity study.

PMID- 12193370
TI  - Lesbian parenting may make a difference.

PMID- 12193371
TI  - Increasing response rates to postal questionnaires. Changing layout of
      questionnaires increases response rates.

PMID- 12193372
TI  - Slang in clinical practice.

PMID- 12193374
TI  - Reproductive biology of the relaxin-like factor (RLF/INSL3).
AB  - The relaxin-like factor (RLF), which is the product of the insulin-like factor 3
      (INSL3) gene, is a new circulating peptide hormone of the relaxin-insulin family.
      In male mammals, it is a major secretory product of the testicular Leydig cells,
      where it appears to be expressed constitutively but in a differentiation
      dependent manner. In the adult testis, RLF expression is a good marker for fully
      differentiated adult-type Leydig cells, but it is only weakly expressed in
      prepubertal immature Leydig cells or in Leydig cells that have become
      hypertrophic or transformed. It is also an important product of the fetal Leydig
      cell population, where it has been demonstrated using knockout mice to be
      responsible for the second phase of testicular descent acting on the
      gubernaculum. INSL3 knockout mice are cryptorchid, and in estrogen-induced
      cryptorchidism, RLF levels in the testis are significantly reduced. RLF is also
      made in female tissues, particularly in the follicular theca cells of small
      antral follicles and in the corpus luteum of the cycle and pregnancy. The
      ruminant ovary has a very high level of RLF expression, and analysis of primary
      cultures of ovarian theca-lutein cells indicated that, as in the testis,
      expression is probably constitutive but differentiation dependent. Female INSL3
      knockout mice have altered estrous cycles, where RLF may be involved in follicle
      selection, an idea strongly supported by observations on bovine secondary
      follicles. Recently, a novel 7-transmembrane domain receptor (LGR8 or Great) has
      been tentatively identified as the RLF receptor, and its deletion in mice leads
      also to cryptorchidism.

PMID- 12193373
TI  - Steroid modulation of astrocytes in the neonatal brain: implications for adult
      reproductive function.
AB  - There is a growing appreciation for the importance of astrocytes, a type of
      nonneuronal glial cell, to overall brain functioning. The ability of astrocytes
      to respond to gonadal steroid hormones with changes in morphology has been well
      documented in the adult brain. It is also apparent that astrocytes of the
      developing brain are permanently differentiated by the neonatal hormonal milieu,
      in particular by estradiol, resulting in sexually dimorphic cell morphology,
      synaptic patterning, and density in males and females. The mechanisms of
      hormonally mediated astrocyte differentiation are likely to be region specific.
      In the arcuate nucleus of the hypothalamus, neuron-to-astrocyte signaling appears
      to play a critical role in estradiol-induced astrocyte differentiation during the
      first few days of life. Gamma aminobutyric acid (GABA) is an amino acid
      neurotransmitter that is synthesized and released exclusively by neurons. The
      levels of GABA are increased in the arcuate nucleus of neonatal males versus
      females. Preventing the increase in males or mimicking GABA action in females
      modulates astrocytes accordingly. Speculation about and evidence in support of
      the functional significance of this dimorphism to adult reproductive functioning
      is the topic of this review.

PMID- 12193375
TI  - Differential alteration of the reproductive axis by testosterone and estrogen in
      peripubertal and adult male Siberian hamsters (Phodopus sungorus).
AB  - In male Siberian hamsters, administration of adult physiological levels of
      testosterone (T) and estrogen (E2) to juveniles inhibited pubertal onset by
      distinct pathways. It is presently unclear if T and E2 also exert an inhibitory
      effect on the reproductive function of sexually mature and sexually maturing
      hamsters. This study aims to determine if there is an age-dependent decline in
      the sensitivity of the hypothalamic-pituitary-gonadal (HPG) axis to these
      inhibitory steroids and if their actions remain distinct. Peripubertal and adult
      male Siberian hamsters were implanted with a silastic capsule containing T, E2,
      or cholesterol (Ch, control). Testosterone treatment significantly reduced testes
      mass and length and impaired spermatogenesis in both ages. In contrast, E2
      treatment reduced testes mass only in peripubertal, but not adult, animals. In
      fact, E2 treatment significantly increased testes mass in adults without altering
      spermatogenesis. In addition, circulating E2 is very high immediately prior to
      pubertal onset and declines thereafter. Our results showed the inhibitory effects
      of T persist into adulthood whereas those of E2 subside as the animals become
      sexually mature. The decreased sensitivity of the HPG axis to the inhibitory
      effects of E2 in adult animals and the high level of circulating E2 immediately
      prior to pubertal onset suggest E2 may play an important role in the regulation
      of puberty in this species.

PMID- 12193376
TI  - Electroporated transgene-rescued spermatogenesis in infertile mutant mice with a
      sertoli cell defect.
AB  - The molecular basis of most human male infertility arising from spermatogenesis
      disruption is poorly understood because of a lack of useful investigation
      systems. To study the roles of the supporting Sertoli cells in mammalian
      spermatogenesis, we improved an electroporation technique for seminiferous
      tubules in vivo. Because Sertoli cells barely proliferate in mature testis,
      linear transgenes are not incorporated into the genome and quickly degrade.
      However, circular expression vector is stably expressed in Sertoli cells for a
      long period. By electrotransformation of a complete cDNA, we rescued defective
      spermatogenesis in infertile Sl(17H)/Sl(17H) mutant mice with partial dysfunction
      of stem cell factor in Sertoli cells. Application of this gene transfer system
      will facilitate both the understanding of spermatogenesis and the development of
      new gene therapies for human male infertility.

PMID- 12193377
TI  - Activation of mitogen-activated protein kinases and AP-1 transcription factor in
      ovotoxicity induced by 4-vinylcyclohexene diepoxide in rats.
AB  - Previous studies have demonstrated that ovotoxicity induced in small preantral
      (primordial and primary) ovarian follicles by 4-vinylcyclohexene diepoxide (VCD)
      in rats is likely via acceleration of the normal process of atresia (apoptosis).
      This acceleration is associated with increased activities of caspase cascades,
      changes in subcellular distribution of Bcl-2 family members, and alteration of
      estrogen receptor-mediated signaling pathways. The present study was designed to
      investigate possible effects of VCD dosing on the mitogen-activated protein
      kinases (MAPK)/AP-1 signaling pathways in rat ovarian small follicles. Female
      F344 rats were given a single dose of VCD (80 mg/kg i.p., 1 day--a time when
      ovotoxicity has not been initiated) or dosed daily for 10 or 15 days (80 mg/kg
      i.p.; 10 days--a time when the earliest signs of impending follicular destruction
      is seen, 15 days--a time when significant ovotoxicity is underway). Four hours
      following the final dose, ovaries and livers were collected. Ovarian small (25
      100 microm) and large (100-250 microm) preantral follicles were isolated, and
      cytosolic or nuclear extracts were prepared from follicles and livers for
      analyses. Activities of MAPKs, including extracellular signal-regulated kinase, c
      Jun N-terminal protein kinase (JNK), and p38 kinase, were determined in
      follicular and liver cytosolic extracts, and AP-1 DNA binding activity was
      determined in follicular and liver nuclear extracts. Compared with control, a
      single dose of VCD caused a decrease in JNK activity and an increase of AP-1
      binding activity in isolated small ovarian follicles. After repeated daily dosing
      with VCD for 10 or 15 days, JNK and p38 kinase activities in small ovarian
      follicles were increased (p38 kinase: 1.64 +/- 0.14 for 10 days, 1.48 +/- 0.11
      for 15 days, VCD/control, P < 0.01; JNK: 1.44 +/- 0.11 for 10 days, 1.37 +/- 0.06
      for 15 days, VCD/control, P < 0.01) and AP-1 binding activity in small ovarian
      follicles was decreased (10 days, 0.29 +/- 0.04; 15 days, 0.51 +/- 0.04,
      VCD/control, P < 0.01). VCD did not affect any of these measurements in large
      preantral follicles or liver. Phosphorylation status of c-Jun protein as measured
      by Western blotting was increased (1.22 +/- 0.1, VCD/control, P < 0.05) after the
      15-day daily dosing with VCD, but total c-Jun protein levels were unaffected.
      Using antibodies against c-Jun or phospho-c-Jun for supershift DNA binding assay,
      c-Jun and phospho-c-Jun were identified in the AP-1-DNA binding complex, and the
      binding activity was reduced in tissues with increased phospho-c-Jun protein
      levels. Taken together, these data provide evidence that accelerated atretic
      signals induced by VCD is associated with MAPK/AP-1 signaling pathways and
      phosphorylation of c-Jun plays a significant role in transmitting the apoptotic
      signals.

PMID- 12193378
TI  - Regulation of human glycoprotein hormone alpha-subunit gene transcription in
      LbetaT2 gonadotropes by protein kinase C and extracellular signal-regulated
      kinase 1/2.
AB  - Transcriptional activation of the human glycoprotein hormone alpha-subunit
      (alphaGSU) promoter in response to GnRH and phorbol-12-myristate-13-acetate (PMA)
      has been well characterized in alphaT3-1 gonadotropes but not investigated in the
      more differentiated LbetaT2 clonal gonadotrope. We have evaluated alphaGSU
      transcription in the more mature LbetaT2 cell line, using deletion and
      heterologous constructs of the alphaGSU promoter linked to a luciferase reporter
      gene. Basal alphaGSU-promoter activity was significantly less in LbetaT2 cells
      than in alphaT3-1 cells, but stimulation of transfected cells with GnRH and PMA
      resulted in similar increases in alphaGSU-promoter activity. Deletional analysis
      of the human alphaGSU promoter in LbetaT2 cells indicated that sequences between 
      398 and -244 and between -244 and -195 base pairs (bp) were involved in
      regulating basal alphaGSU-promoter transcription, whereas the region between -244
      and -195 bp regulated PMA-stimulated promoter activity. Deletion of this promoter
      region containing a steroidogenic factor-1 (SF-1) binding site abolished basal
      and PMA-stimulated transcription. Site-directed mutagenesis of the SF-1 binding
      site resulted in a significant attenuation of basal and PMA-stimulated alphaGSU
      transcription. Pretreatment of LbetaT2 cells with a mitogen-activated protein
      kinase kinase-specific inhibitor, U0126, abolished the PMA-stimulated increase in
      MAPK activity and significantly reduced basal and PMA-stimulated promoter
      activity. Electrophoretic mobility shift assays for SF-1 and GATA revealed that
      PMA failed to affect SF-1 binding but enhanced GATA binding to a consensus GATA
      oligonucleotide, an effect that was blocked with U0126 pretreatment, suggesting
      that GATA may mediate ERK activation of alphaGSU transcription. Our data suggests
      that, in the mature LbetaT2 gonadotrope cell line, two regions of the human
      alphaGSU promoter regulate basal transcription and that SF-1 is involved in
      mediating basal and PMA-stimulated promoter activity. Furthermore, PKC-stimulated
      transcription partially relies on ERK acting on elements downstream of -244 bp of
      the human alphaGSU promoter.

PMID- 12193379
TI  - Cellular turnover in the rat uterine cervix and its relationship to estrogen and
      progesterone receptor dynamics.
AB  - Histoarchitectural changes of the uterine cervix allow its successful adaptation
      to different physiological conditions. In this study, we evaluated cell turnover
      in each cellular compartment of the uterine cervix in association with steroid
      hormone receptor expression in order to establish the range of physiological
      changes. Proliferation, apoptosis, and progesterone receptor (PR) and estrogen
      receptor alpha (ERalpha) expression were evaluated in cycling, pregnant, and
      postpartum rats. In estrus and diestrus II, ERalpha and PR expression exhibited
      variations according to the region evaluated. Proliferation and apoptosis showed
      a reciprocal pattern, the epithelium being the region with higher cell turnover.
      High apoptotic index (AI) in estrus was associated with the lowest ERalpha and
      the highest PR scores. During pregnancy, proliferation of the epithelium was the
      predominant event and AI was low. On Postpartum Day 1 (PPD1), proliferation
      decreased while apoptosis increased. As described for the estrous cycle, during
      pregnancy and PPD1, AI and ERalpha were negatively correlated. In the
      fibroblastic stroma, low proliferation was observed throughout pregnancy;
      however, there was a net increase in cell number because very few cells underwent
      apoptosis. No difference in ERalpha was observed in fibroblastic cells during
      pregnancy and postpartum; however, a great decrease of this receptor in the
      epithelial compartment was observed after delivery. Unlike cervical epithelium,
      PR was highly expressed in stromal cells. At term, a dramatic increase in
      epithelial PR was observed. While epithelial PR remained high on PPD1, a decrease
      was observed in muscle stroma. These results show that, in all stages studied, 1)
      ERalpha and PR have different patterns of expression with differential responses
      to signals that modulate proliferation and/or apoptosis depending on the cellular
      compartment, and 2) even though the epithelium is the region with the highest
      cell turnover, the fibroblastic and muscle stroma are active regions that have
      their own patterns of behavior.

PMID- 12193381
TI  - Apoptosis during spontaneous and prostaglandin F(2alpha)-induced luteal
      regression in the buffalo cow (Bubalus bubalis): involvement of mitogen-activated
      protein kinases.
AB  - The present study was conducted to evaluate whether the corpus luteum (CL) of the
      water buffalo (Bubalus bubalis) cow undergoes luteal regression by the process of
      apoptosis and to examine the involvement of mitogen-activated protein (MAP)
      kinases during prostaglandin (PG) F(2alpha)-induced luteolysis. Sections of CL
      from late in the estrous cycle, i.e., during spontaneous luteolysis, stained for
      4',6'-diamidino-2-phenylindole revealed increased numbers of condensed nuclei,
      indicating cell death by apoptosis, which was confirmed further by the occurrence
      of pronounced oligonucleosome formation. For morphological and biochemical
      characterization during PGF(2alpha)-induced apoptosis, CL were collected at 0, 4,
      12, and 18 h after injection of 750 micro g of Tiaprost, a synthetic analogue of
      PGF(2alpha), to midestrous buffalo cows. Serum progesterone concentrations fell
      within 4 h and decreased (P < 0.05) maximally by 18 h. Concomitant decreases (P <
      0.05) in the levels of steroidogenic acute regulatory mRNA and protein were
      observed in CL during 12-18 h, with the more profound effect on mRNA levels.
      Quantitative analysis of the genomic DNA showed a >5-fold increase (P < 0.05) in
      the low molecular weight DNA fragments by 18 h postinjection. Immunoblot analysis
      of CL tissue lysates showed increased (P < 0.05) levels of phospho-Jun N-terminal
      kinase (JNK) 1 (4- to 14-fold during 4-18 h) and phospho-p38 (2- to 4-fold at 18
      h). Immunohistochemical evaluation of CL sections revealed an increased nuclear
      localization of phospho-JNK after treatment. These findings demonstrate that the
      CL of the buffalo cow undergoes cell death by the process of apoptosis both
      during spontaneous and PGF(2alpha)-induced luteolysis and that MAP kinases are
      involved during PGF(2alpha)-mediated apoptosis in the CL.

PMID- 12193380
TI  - Characterization of integrin expression in the mouse ovary.
AB  - Integrin alpha:beta heterodimers mediate cell contacts to the extracellular
      matrix and initiate intracellular signaling cascades in response to a variety of
      factors. Integrins interact with many determinants of cellular phenotypes and
      play roles in controlling the development, structural integrity, and function of
      every type of tissue. Despite their importance, little is known about the
      regulation of integrin subunits in the mammalian ovary and how they function in
      folliculogenesis. To determine their relevance to ovarian physiology, we have
      studied the expression of integrin subunit mRNAs by Northern blot analysis and in
      situ hybridization in ovaries of wild-type, growth differentiation factor 9 (Gdf
      9) knockout, FSHbeta (Fshb) knockout, and inhibin alpha (Inha) knockout mice.
      Integrin alpha6 mRNA is expressed in oocytes and granulosa cells of single-layer
      follicles and in oocytes and theca cells of multilayer follicles. Integrin alpha6
      is highly expressed in Gdf 9 knockout ovaries, which are enriched in oocytes and
      primary (single layer) follicles because of a block at this stage of follicular
      development. Integrin alpha(v) mRNA is most highly expressed in the granulosa
      cells of multilayer growing follicles, and therefore only low levels of
      expression are detectable in the Gdf 9 knockout ovaries. Integrin beta1 mRNA
      exhibits a broad expression pattern in ovaries, including oocytes, granulosa
      cells, theca cells, and corpora lutea. Integrin beta3 mRNA is expressed in theca
      and interstitial cells and is upregulated in corpora lutea. It is nearly
      undetectable in ovaries of Fshb knockout mice, which develop preantral follicles
      but have no luteal cells. Integrin beta5 mRNA is predominantly expressed in
      granulosa cells of multilayer follicles. It is expressed at high levels in the
      Fshb knockout mice and in a compartmentalized manner in the granulosa
      cell/Sertoli cell tumors that develop in the Inha knockout mice. Specific
      integrins are associated with ovarian cellular phenotypes in mice, which raises
      intriguing possibilities as to integrin functions in oocyte competence,
      follicular development, luteinization, and granulosa cell proliferation.

PMID- 12193382
TI  - Analysis of the mechanism for chromatin remodeling in embryos reconstructed by
      somatic nuclear transfer.
AB  - The objective of the present study was to understand the molecular/biochemical
      nature of chromatin remodeling that occurs in the somatic nuclei transferred into
      oocytes. We produced the reconstructed mouse embryos by two different protocols
      of nuclear transfer. The nucleus of a cumulus cell was transferred into
      enucleated unfertilized oocytes (transferred before activation, TA protocol) or
      activated oocytes (activated before transfer, AT protocol). More than half
      (56.1%) of the embryos reconstructed using the TA protocol developed to the
      morula/blastocyst stage, whereas very few (1.0%) of the embryos reconstructed
      using the AT protocol reached the morula/blastocyst stage. These embryos were
      analyzed for the events associated with transcriptional regulation. Changes in
      transcriptional activity, nuclear accumulation of TATA box binding protein (TBP),
      and DNase I sensitivity were examined after nuclear transfer. In the embryos
      reconstructed by TA protocol, all of these events occurred in a manner similar to
      that in the control diploid parthenogenetic embryos. The transcriptional activity
      was silenced after nuclear transfer and resumed at the late 1-cell stage. TBP was
      displaced and subsequently accumulated at the early and the late 1-cell stage,
      respectively. DNase I sensitivity was increased and then decreased at the early
      and late 1-cell stage, respectively. In contrast, embryos reconstructed using the
      AT protocol did not show such changes in transcriptional activity, TBP
      accumulation, and DNase I sensitivity. These events would be necessary for
      differentiated nuclei to restore totipotency and are useful indices to evaluate
      successful chromatin remodeling.

PMID- 12193383
TI  - Cellular and molecular deviations in bovine in vitro-produced embryos are related
      to the large offspring syndrome.
AB  - The large offspring syndrome (LOS) is observed in bovine and ovine offspring
      following transfer of in vitro-produced (IVP) or cloned embryos and is
      characterized by a multitude of pathologic changes, of which extended gestation
      length and increased birthweight are predominant features. In the present study,
      we used bovine blastocysts to analyze cellular parameters, i.e., the number of
      cells in Day 7 blastocysts and the size of Day 12 elongating blastocysts, and
      molecular parameters, i.e., the relative abundance of developmentally important
      genes: glucose transporter (Glut) 1, Glut-2, Glut-3, Glut-4, heat shock protein
      (Hsp) 70.1, Cu/Zn-superoxide dismutase (SOD), histone H4.1, basic fibroblast
      growth factor (bFGF), insulin-like growth factor (IGF) I receptor (R), and IGFII
      R. Some blastocysts were produced by in vitro maturation and fertilization
      followed by in vitro culture in synthetic oviduct fluid medium supplemented with
      BSA or human serum or by in vivo culture in the sheep oviduct. Other blastocysts
      were derived in vivo from the uterine horns of superovulated donors. The findings
      made in the early embryos were related to a representative number of calves
      obtained from each production system and from artificial insemination (AI). In
      vitro culture of bovine embryos in the presence of high concentrations of serum
      or BSA significantly increased the number of cells in Day 7 blastocysts, the size
      of blastocysts on Day 12, and the relative abundance of the transcripts for
      Hsp70.1, Cu/Zn-SOD, Glut-3, Glut-4, bFGF, and IGFI-R when compared with embryos
      from the in vivo production groups. Birthweights of calves derived from IVP
      embryos were significantly higher than those of calves derived from sheep oviduct
      culture, superovulation, or AI. The results support the hypothesis that
      persistence of early deviations in development is causally involved in the
      incidence of LOS, in particular in increased birthweights. The cellular and
      molecular parameters analyzed in this study can be considered early markers of
      LOS in cattle.

PMID- 12193384
TI  - Insulin-like growth factor (IGF)-independent effects of IGF binding protein-4 on
      human granulosa cell steroidogenesis.
AB  - The ovarian insulin-like growth factor (IGF)/IGF binding protein (IGFBP) system
      operates to permit maximal stimulation of steroidogenesis in the dominant
      follicle. In atretic follicles, the predominant IGFBPs are IGFBP-2 and IGFBP-4,
      which appear to be selectively cleaved in healthy follicles. We have recently
      demonstrated potent inhibition by IGFBP-4 of both theca and granulosa cell
      steroid production. The degree to which the inhibition occurred suggested that it
      was greater than might be expected by sequestration of IGF alone. Our study was
      designed to test this idea. Granulosa cells were harvested from follicles
      dissected intact from patients undergoing total abdominal hysterectomy and
      bilateral salpingoophorectomy. Granulosa cells were incubated with or without
      gonadotropins and IGFBP-4 in the presence or absence of either the IGF type I
      receptor blocker alphaIR3 or excess IGFBP-3 to remove the effects of endogenous
      IGF action. Steroid accumulation in the medium was assessed. IGFBP-4 continued to
      exert potent inhibitory effects when the action of endogenous IGF was removed
      from the system, demonstrating that its actions are independent of IGF binding.
      There was no effect on cell metabolism, and the effects on steroidogenesis were
      reversible after IGFBP-4 removal from the culture medium. No similar effects were
      seen with IGFBP-2. These reasults are the first evidence of IGF-independent IGFBP
      4 actions and the first evidence of IGF-independent actions of any IGFBPs in the
      ovary.

PMID- 12193385
TI  - A nicotinic acetylcholine receptor is involved in the arosome reaction of human
      sperm initiated by recombinant human ZP3.
AB  - One of the essential steps in mammalian fertilization is the acrosome reaction
      (AR), a modified exocytotic event in the sperm head that occurs upon contact with
      the glycoprotein matrix of the zona pellucida (ZP) surrounding the oocyte.
      Acetylcholine (ACh) at concentrations of 10-250 micro M and nicotine at 10-250 nM
      significantly initiate the AR of capacitated human sperm. Preincubation with
      three antagonists of the nicotinic acetylcholine receptor (nAChR), alpha
      bungarotoxin (alpha-BTX, 100 nM), alpha-conotoxin IMI (alpha-CTX IMI, 250 nM and
      25 nM), and methyllycaconitine (MLA, 100 nM and 10 nM), significantly blocked AR
      initiation by ACh. alpha-BTX is an anatagonist of several nAChRs, including the
      alpha7 nAChR, and alpha-CTX IMI and MLA are highly specific antagonists of alpha7
      subunit-containing AChRs. The sperm nAChR plays a role in the AR initiated in
      vitro by a purified recombinant human ZP protein (rhZP3). Previously, rhZP3 was
      able to stimulate the AR by mechanisms similar to those seen with native ZP.
      Preincubation of human sperm with alpha-BTX (from 10 micro M to 100 nM), alpha
      CTX IMI (250 and 100 nM), or MLA (100 nM and 10 nM) caused a significant
      inhibition in the rhZP3-initated AR. The inhibition of the ACh-initiated and
      rhZP3-initiated AR by these nAChR antagonists strongly suggests the involvement
      of an alpha7 subunit-containing nAChR in the AR initiated by both ligands. AR
      initiation by progesterone was not inhibited by MLA or alpha-BTX, suggesting that
      this particularnAChR is not involved in the AR initiated by that ligand. In vitro
      results show for the first time that ACh can initiate the human sperm AR and
      strongly suggest that a human sperm alpha7 subunit-containing nAChR plays a role
      in the rhZP3-initiated AR. This nAChR ligand-gated ion channel may be important
      to the signal transduction events of ZP-initiated AR in vivo.

PMID- 12193386
TI  - Src tyrosine kinase-induced loss of luteinizing hormone responsiveness is via a
      Ras-dependent, phosphatidylinositol-3-kinase independent pathway.
AB  - Gonadotropins stimulate gonadal cell steroid secretion primarily through
      activation of a cAMP-protein kinase A signal transduction pathway. Various growth
      factors have been shown to inhibit gonadotropin-stimulated steroidogenesis,
      however, the intracellular signaling cascades involved in growth factor
      inhibition have not been characterized. The present study investigated whether
      Src tyrosine kinase, a nonreceptor tyrosine kinase activated in response to
      growth factor stimulation and previously shown to inhibit LH-stimulated
      progesterone secretion, acts via activation of Ras stimulated pathways,
      phosphatidylinositol-3-kinase (PI3-kinase) stimulated pathways, or both in MA10
      Leydig cells. Direct activation of Src in MA10 cells that express a temperature
      sensitive Src was associated with an increase in GTP-bound Ras, indicating
      increased Ras activity in response to Src activation. Direct activation of Ras by
      way of expression of a constitutively active Ras (Ras+) was associated with a
      decrease in LH responsiveness. Coexpression of a dominant negative Src, which by
      itself increases LH responsiveness in MA10 cells, had no effect on Ras+
      inhibition on LH responsiveness, further demonstrating that Src is upstream of
      Ras. In addition, MA10(Ras+) cells were relatively unresponsive to cholera toxin
      or 8-bromo cAMP, indicating the effects of Ras are independent of cAMP
      generation. Wortmannin, a PI3-kinase inhibitor, did not restore LH responsiveness
      to cells expressing activated Src or constitutively active Ras. These results
      demonstrate that Src activates a Ras pathway in MA10 Leydig cells, and that
      activation of Ras is associated with a loss of LH responsiveness that is
      independent of PI3-kinase.

PMID- 12193387
TI  - Identification and characterization of cystatin-related epididymal spermatogenic
      protein in human spermatozoa: localization in the equatorial segment.
AB  - Our earlier studies in mouse have shown that the cystatin-related epididymal
      spermatogenic (CRES) protein is highly expressed in elongating spermatids in the
      testis and is present in mouse sperm acrosomes, suggesting specific roles in
      sperm function, fertilization, or both. However, whether the human CRES gene is
      similar to that of the mouse and is expressed in germ cells has not yet been
      determined. Therefore, the present study was undertaken to characterize the human
      ortholog of mouse CRES: Northern blot and in situ hybridization experiments
      showed that CRES is highly expressed in the human testis, specifically within
      clusters of round spermatids. Furthermore, reverse transcription-polymerase chain
      reaction detected CRES mRNA in the epididymis. Western blot analysis of protein
      lysates prepared from human testis and ejaculated spermatozoa showed a
      predominant 19-kDa protein and a minor 14-kDa protein. However, in contrast to
      the acrosomal localization of CRES protein in mouse spermatozoa, indirect
      immunofluorescence of human spermatozoa treated with methanol/acetic acid using
      anti-human CRES antibodies revealed that CRES was strictly localized to the
      equatorial segment. Furthermore, the same staining was observed in both
      capacitated and acrosome-reacted spermatozoa. To determine whether CRES was
      associated with the plasma membrane, live spermatozoa were incubated with CRES
      antibody after capacitation and acrosome reaction. Only acrosome-reacted
      spermatozoa showed a weak but specific equatorial staining. Taken together, these
      studies show that CRES protein is present in the sperm equatorial segment and
      becomes accessible to the extracellular environment during fertilization.

PMID- 12193388
TI  - Novel antimicrobial peptide of human epididymal duct origin.
AB  - HE2, a gene expressed specifically in human epididymis, gives rise to multiple
      mRNAs that encode a group of small cationic secretory peptides. Localization of
      HE2 within the defensin gene cluster and prediction that beta-defensin-like
      modules exist suggest that these peptides have antimicrobial activity and
      represent components of the innate epithelial defense system of the epididymal
      duct. Reverse transcription-polymerase chain reaction analysis confirmed the
      occurrence of eight human HE2-derived transcripts, including minor mRNA variants,
      that had previously been shown only in animal species. Employing isoform-specific
      antibodies against the predicted HE2 products, multiple 4- to 8-kDa peptides were
      detected in human epididymal epithelium, epididymal fluid, and ejaculate. N
      terminal microsequencing has suggested a proteolytic processing of these peptides
      by a furin-like proprotein convertase, which cleaves a propiece from the longer
      precursor peptides. HE2alpha and HE2beta1, representing major peptide isoforms in
      the human epididymis, were recombinantly expressed, and their susceptibility to
      furin cleavage was demonstrated in vitro and in vivo. Processed recombinant
      peptides and chemosynthetic fragments were included in antimicrobial tests. In
      addition to the beta-defensin-like HE2beta1 with its expected antibacterial
      function, HE2alpha C-terminal fragments showed antibacterial activity against
      Escherichia coli, although it showed no significant similarity to beta-defensins
      nor to any other known protein family.

PMID- 12193389
TI  - CRM1-mediated nuclear export is present during porcine embryogenesis, but is not
      required for early cleavage.
AB  - Regulated movement of cellular factors between the cytoplasm and nucleus is
      required for fundamental cellular processes ranging from cell cycle control to
      transcriptional regulation. CRM1 is a nuclear export factor whose function is to
      actively transport nuclear cargos that bear nuclear export sequences to the
      cytoplasm. Because CRM1 likely plays a role in the intracellular regulation of
      many cellular processes, we set out to characterize CRM1 function during early
      mammalian embryogenesis. A series of embryo culture experiments that employed a
      specific inhibitor of CRM1, leptomycin B, indicated that CRM1 function is not
      required for development until after the 4-cell stage of porcine embryo
      development. Immunolocalization of CRM1 in fixed embryos revealed that CRM1 is
      localized in a unique pattern during the period of time when the embryo does not
      have a developmental requirement for CRM1. Despite these findings, a
      microinjection assay showed that CRM1 function persists during this period of
      development. This demonstrates that although CRM1 is present in a functional form
      throughout mammalian embryo development, its function is not required for early
      cleavage.

PMID- 12193390
TI  - Stage-specific expression of genes associated with rat spermatogenesis:
      characterization by laser-capture microdissection and real-time polymerase chain
      reaction.
AB  - Spermatogenesis in the rat consists of 14 unique morphologic cellular
      associations between Sertoli cells and developing germ cells within the
      seminiferous epithelium. The complexity of the cellular associations leads to
      difficulty in the isolation of individual cells at a defined stage of development
      for the study of their unique patterns of gene or protein expression. Thus, laser
      capture microdissection is an ideal technique to permit such analysis. This study
      used laser-capture microdissection and real-time reverse transcription-polymerase
      chain reaction (RT-PCR) to quantitate the stage-specific expression of a series
      of genes of functional significance in hormonal regulation and cell-cell
      interactions in spermatogenesis, including cathepsin-L, CREM-tau, transition
      protein-1, androgen receptor, beta1-integrin, N-cadherin, and hypoxanthine
      phosphoribosyltransferase (HPRT). Frozen sections (10 micro m) were obtained from
      normal adult rat testes. Laser-capture microdissection (LCM) was used to capture
      all cells in cross-sections of seminiferous tubules that were grouped into stages
      I-V, VII-VIII, and IX-XIII. Transition protein-1 expression was lowest during
      stages I-V and increased 5.9-fold during stages VII-VIII and IX-XIII (P < 0.01).
      Cathepsin-L expression was highest during stages I-V and VII-VIII, falling 4.9
      fold during stages IX-XIII (P < 0.05). Similarly, CREM-tau expression was highest
      during stages I-V and VII-VIII, falling 1.6-fold during stages IX-XIII (P <
      0.05). A novel CREM-tau isoform lacking the phosphorylation domain was also
      characterized but was not stage-specific. beta1-Integrin, N-cadherin, and
      androgen receptor expression did not change between the spermatogenic stages
      examined. HPRT housekeeper expression was lowest during stages I-V but increased
      1.5-fold during stages VII-VIII and IX-XIII (P < 0.05). This study is the first
      to apply LCM and real-time RT-PCR analysis to quantitate stage-specific changes
      in the expression of multiple genes in the seminiferous epithelium.

PMID- 12193391
TI  - Influence of estradiol on NADPH diaphorase/neuronal nitric oxide synthase
      activity and colocalization with progesterone or type II glucocorticoid receptors
      in ovine hypothalamus.
AB  - Nitric oxide (NO) has been shown to play an important role in both the
      neuroendocrine reproductive and stress axes, which are closely linked. Because
      progesterone (P4) receptors (PRs) and glucocorticoid receptors (GRs) are not
      found in GnRH neurons and the NOergic system has been implicated in the control
      of GnRH secretion, this study aimed to ascertain whether steroids altered the
      NOergic system. Our first objective was to map the distribution of NO synthase
      (NOS) cells in the ovine preoptic area (POA) and hypothalamus and to determine
      whether NOS activity is enhanced by estradiol (E2) treatment. Using NADPH
      diaphorase (NADPHd) histochemistry, we found that NADPHd-positive neurons were
      spread throughout the ovine POA and hypothalamus, and that all NADPHd cells were
      immunoreactive for NOS. In response to estradiol, a significant increase in the
      number of NADPHd cells was noted only in the ventrolateral region of the
      ventromedial nucleus (VMNvl), with no significant difference in the POA or
      arcuate nucleus. Progesterone and glucocorticoid receptors were colocalized with
      NADPHd reactive neurons in the POA, arcuate nucleus, and VMNvl of ewes in both
      treatment groups. In ewes receiving estradiol, the number of NADPHd-positive
      cells containing steroid receptors in the POA (PR, 81%; GR, 79%) and arcuate
      nucleus (PR, 89%; GR, 84%) was similar, but in the VMNvl, fewer NADPHd-positive
      cells contained GR (PR, 88%, GR, 31%). These data show that estradiol up
      regulates NOS activity in a site-specific manner and that the influence and
      possible interaction of progesterone and corticosteroids on NO producing cells
      may differ according to the neural location.

PMID- 12193392
TI  - Ionic currents activated via purinergic receptors in the cumulus cell-enclosed
      mouse oocyte.
AB  - Several chemical signals synthesized in the ovary, including neurotransmitters,
      have been proposed to serve as regulators of folliculogenesis, however, their
      mechanisms of action have not been completely elucidated. Here,
      electrophysiological and molecular biology techniques were used to study
      responses generated via purinergic stimulation in cultured mouse cumulus cell
      enclosed oocytes (CEOs). Application of extracellular ATP elicited depolarizing
      responses in CEOs. Using the voltage clamp technique by impaling oocytes with two
      microelectrodes, we determined that these responses were mainly due to activation
      of two distinct ionic currents. The first corresponded to the opening of Ca2+
      dependent Cl- channels (I(Cl(Ca))) and the second to the opening of Ca2+
      independent channels that are permeable to Na+ (I(c+)). The potency order for
      different nucleotides (50 micro M) was UTP > ATP > 2meS-ATP > ADP, and
      alpha,betame-ATP and adenosine were found to be inactive. Suramin (100 micro M)
      blocked the response elicited by ATP or UTP. In addition, voltage dependent K+
      currents activated by depolarization of CEOs were characterized. All CEO ionic
      currents recorded from the oocyte were completely inhibited by octanol (1 mM), a
      gap junction blocker. Thus, purinergic responses and K+ currents originate mainly
      in the membrane of cumulus cells. Transcripts of the purinergic receptor P2Y2
      subtype were amplified by polymerase chain reaction from the cDNA of granulosa
      cells or cumulus cells. This study shows that P2Y2 receptors are expressed in
      CEOs, and that their stimulation opens at least two different types of ion
      channels. Both the ion channels and the receptors seemed to be located in the
      cumulus cells, which transmit their corresponding electrical signals to the
      oocyte via gap junction channels.

PMID- 12193393
TI  - Expression of interferon receptor subunits, IFNAR1 and IFNAR2, in the ovine
      uterus.
AB  - Interferon-tau (IFN-tau) is the antiluteolytic factor released by concepti of
      ruminant ungulate species prior to implantation. All type I interferons,
      including IFN-tau, exert their action through a common receptor, which consists
      of two subunits, IFNAR1 and IFNAR2c, but the distribution of the two polypeptides
      in uterine endometrium has not been examined. In situ hybridization and
      immunohistochemistry on sections from pregnant and nonpregnant ovine uteri at
      Days 14 and 15 after estrus and mating showed that both IFNAR1 and IFNAR2 mRNA
      and protein were strongly expressed in endometrial luminal epithelium (LE),
      superficial glandular epithelium (GE), and stromal cells, within but not outside
      caruncles. Similar staining patterns were noted in pregnant and nonpregnant uteri
      for both subunits. Western blot analysis of membrane fractions from cell lines
      derived from endometrial LE, GE, and stromal cells, and affinity cross-linking
      experiments with radioactively labeled IFN-tau performed on crude endometrial
      membranes indicated the presence of both high ( approximately 110 kDa) and low
      (75-80 kDa) molecular mass forms of the two receptor subunits. To localize where
      IFN-tau binds when it is introduced into the uterine lumen, immunohistochemistry
      with an antiserum against IFN-tau was performed on sections of uteri from Day 14
      nonpregnant ewes whose uteri had previously been infused with IFN-tau. Staining
      was concentrated on the LE and superficial GE cells, and was absent from the
      deeper regions of the glands and from the stromal tissues. These studies
      demonstrate the heavy concentration of IFNAR1 and IFNAR2 in cells of the LE and
      superficial GE, which appear to be the main targets for IFN-tau.

PMID- 12193394
TI  - Germ cell and dose-dependent DNA damage measured by the comet assay in murine
      spermatozoaa after testicular X-irradiation.
AB  - The single-cell gel electrophoresis (Comet) assay has been widely used to measure
      DNA damage in human sperm in a variety of physiological and pathological
      conditions. We investigated the effects of in vivo radiation, a known genotoxin,
      on spermatogenic cells of the mouse testis and examined sperm collected from the
      vas deferens using the neutral Comet assay. Irradiation of differentiating
      spermatogonia with 0.25-4 Gy X-rays produced a dose-related increase in DNA
      damage in sperm collected 45 days later. Increases were found when measuring
      Comet tail length and percentage of tail DNA, but the greatest changes were in
      tail moment (a product of tail length and tail DNA). Spermatids, spermatocytes,
      differentiating spermatogonia, and stem cell spermatogonia were also irradiated
      in vivo with 4 Gy X-rays. DNA damage was indirectly deduced to occur at all
      stages. The maximum increase was seen in differentiating spermatogonia. DNA
      damaged cells were, surprisingly, still detected 120 days after stem cell
      spermatogonia had been irradiated. The distribution of DNA damage among
      individual sperm cells after irradiation was heterogeneous. This was seen most
      clearly when changes in the Comet tail length were measured when there were
      discrete undamaged and damaged populations. After increasing doses of
      irradiation, an increasing proportion of cells were found in the damaged
      population. Because a proportion of undamaged sperm cells remains after all but
      the highest dose, the possibility of normal fertility remains. However,
      fertilization with a spermatozoa carrying high amounts of DNA damage could lead
      to effects as diverse as embryonic death and cancer susceptibility in the
      offspring.

PMID- 12193395
TI  - Follicle and endocrine dynamics during experimental follicle deviation in mares.
AB  - Deviation during a follicular wave in mares begins when the largest follicle (F1)
      reaches a mean diameter of 22.5 mm and is characterized by continued growth of F1
      to become the dominant follicle and regression of F2 to become the largest
      subordinate follicle. In the present study, F1 was ablated at the expected
      beginning of deviation (Hour 0) to provide a reference point for characterizing
      the intrafollicular changes preceding experimental deviation between F2 and F3.
      Diameters and concentrations of follicular fluid factors in F2 and F3 were
      determined in F1-ablated mares at Hours 0, 12, 24, 48, or 72 (n = 8 mares/group).
      Circulating FSH concentrations were greater (P < 0.05) in the Hour 72 ablation
      group than in controls 12 h after ablation and then progressively decreased. The
      diameters of F2 and F3 increased (P < 0.05) during Hours 0 to 24. Thereafter, F2
      continued to increase but F3 did not, indicating that experimental deviation
      began at Hour 24. The diameter of F2 and circulating FSH concentration at Hour 24
      were similar (P > 0.1) to the diameter of F1 and FSH concentration at Hour 0,
      respectively. A differential change between F2 and F3 was not detected in
      follicular fluid concentrations of estradiol, inhibin-A, and activin-A by the
      beginning of experimental deviation. However, estradiol was higher in F2 at Hours
      0 and 12 and inhibin-A was higher in F2 throughout the experiment, and both
      factors could have been involved in experimental deviation. Free insulin-like
      growth factor-1 (IGF-1) increased (P < 0.05) in F2 beginning at Hour 12 and was
      higher (P < 0.05) in F2 than in F3 by the beginning of experimental deviation.
      Temporally, this result indicated that intrafollicular IGF-1 was involved in
      conversion of F2 from a destined subordinate follicle to a dominant follicle.

PMID- 12193396
TI  - Ontogeny and regulation of ovine placental prostaglandin E2 synthase.
AB  - Recent evidence suggests that ovine placental output of prostaglandin (PG) E2
      rises through late gestation partly because of a direct effect of cortisol on
      PGH2 synthase 2 (PGHS-2) expression and activity within trophoblast tissue.
      Synthesis of PGE2 is also dependent, however, on PGE2 synthase (PGES), which
      converts PGH2 to PGE2. We hypothesized that PGES is expressed in the ovine
      placenta, and that, similar to PGHS-2, expression increases through gestation and
      is regulated positively by cortisol. Placental tissues from pregnant ewes in mid
      and late gestation, at term, and during early and active labor were analyzed to
      determine the gestational profile of PGES. The regulation of PGES expression was
      assessed in placental tissues from pregnant ewes in which intrafetal cortisol
      infusion was administered in late gestation, in the presence or absence of an
      aromatase inhibitor, to block the cortisol-stimulated rise in estradiol.
      Expression of PGES was analyzed by in situ hybridization, Western blot analysis,
      and immunohistochemistry. In the placentome, PGES localized to fetal trophoblast
      cells and endothelial cells in maternal blood vessels, consistent with its
      contribution to the rise in placental PGE2 output toward the onset of labor and
      with a role of PGE2 in the local regulation of uteroplacental blood flow,
      respectively. Expression of PGES mRNA and protein increased with gestation.
      However, there was no significant further change with labor or during cortisol
      infusion in the presence or absence of a rise in fetal plasma estradiol, in
      contrast to reported changes in PGHS-2. These results suggest that PGES is not
      coregulated with PGHS-2 in the sheep placenta at term. The progressive increase
      in PGES, however, likely contributes to the rise in circulating PGE2 in the fetus
      in late pregnancy.

PMID- 12193397
TI  - Retrovirus-mediated modification of male germline stem cells in rats.
AB  - The ability to isolate, manipulate, and transplant spermatogonial stem cells
      provides a unique opportunity to modify the germline. We used the rat-to-nude
      mouse transplantation assay to characterize spermatogonial stem cell activity in
      rat testes and in culture. Our results indicate that rat spermatogonial stem
      cells can survive and proliferate in short-term culture, although a net loss of
      stem cells was observed. Rat spermatogonial stem cells also were susceptible to
      transduction with a retroviral vector carrying a lacZ reporter transgene. Using a
      3-day periodic infection protocol, 0.5% of stem cells originally cultured were
      transduced and produced transgenic colonies of spermatogenesis in recipient mouse
      testes. The level of transgenic donor-derived spermatogenesis observed in the rat
      to-mouse transplantation was similar to levels that produced transgenic progeny
      in the mouse-to-mouse transplantation. This work provides a basis for
      understanding the biology of rat spermatogonial stem cells. Development of an
      optimal rat recipient testis model and application of these methods for germline
      modification will enable the production of transgenic rats, potentially valuable
      tools for evaluating genes and their functions. In addition, these methods may be
      applicable in other species where existing transgenic methods are inefficient or
      not available.

PMID- 12193398
TI  - Hereditary defects in both germ cells and the blood-testis barrier system in as
      mutant rats: evidence from spermatogonial transplantation and tracer-permeability
      analysis.
AB  - The rat mutant allele as is located on chromosome 12. Homozygous (as/as) males
      show arrested spermatogenesis, mainly at the pachytene spermatocyte stage. It is
      not clear whether this defective spermatogenesis is caused by a failure in a
      somatic cell component that supports spermatogenesis or in the germ cell itself.
      Spermatogonial transplantation was performed to identify the genetically
      defective site in the as/as testis. In experiment 1, germ cells collected from
      as/as testes were transplanted into the testes of immunodeficient mice and normal
      rats. In experiment 2, normal rat germ cells were transplanted into as/as testes.
      The results of experiment 1 showed arrest of spermatogenesis at the pachytene
      spermatocyte stage, accompanied by a characteristic morphological feature, i.e.,
      the formation of inclusion-like bodies in the cytoplasm, in both rat and mouse
      recipients. These results revealed the intrinsic effect of the mutant gene(s) on
      germ cells. In experiment 2, no restoration of spermatogenesis was detected in
      the recipient testes despite thorough histological examination. These results
      suggest that defects in a somatic cell component in as/as testes prevent the
      donor germ cells from colonizing and regaining their spermatogenetic ability.
      When the seminiferous epithelium of the as/as testis was examined by electron
      microscopy, no morphological abnormalities, including the formation of
      ectoplasmic specializations between adjacent Sertoli cells, were observed in the
      somatic cell components. However, when cytochrome c was applied as a tracer
      material, it penetrated the tight junctions between the Sertoli cells, indicating
      dysfunction of the blood-testis barrier in the as/as testis. The lack of
      restoration of spermatogenesis in the as/as testis after transplantation of
      normal germ cells may have been caused by the unfavorable environment in the
      seminiferous epithelium resulting from the incomplete barrier system between
      adjoining Sertoli cells. The gene(s) at the as locus may have a role in both germ
      cell differentiation and the establishment of the blood-testis barrier.

PMID- 12193399
TI  - Increased level of matrix metalloproteinases 2 and 9 in the ripening process of
      the human cervix.
AB  - The human uterine cervix is a fibrous organ with a high connective tissue
      content. An extensive remodeling of the connective tissue prior to parturition,
      i.e., cervical ripening, requires the presence of proteolytic enzymes. The exact
      mechanism of cervical ripening has not been clarified. We evaluated in vivo
      distribution and expression of matrix metalloproteinases 2 and 9 (MMP-2 and MMP
      9) in the human cervix at term pregnancy and immediately after parturition
      compared with the nonpregnant state. Cervical biopsies were obtained from term
      pregnant, postpartum, and nonpregnant women. MMP-2 and MMP-9 proteins were
      localized by immunohistochemistry. Messenger RNA levels of MMP-2 and MMP-9 were
      evaluated by relative quantitative reverse transcription-polymerase chain
      reaction (RT-PCR) using an invariable internal standard. The mRNA levels of MMP-2
      and MMP-9 were increased in the cervix at term pregnancy and postpartum compared
      with the nonpregnant state. Cervical stromal fibroblasts and smooth muscle cells
      were identified as main sources of MMP-2, whereas the MMP-9 protein was observed
      exclusively in invading leukocytes. These data indicate the involvement of MMP-2
      and MMP-9 in the cervical ripening process.

PMID- 12193400
TI  - A 3'-truncated transferrin messenger RNA is expressed in rat testicular germ
      cells.
AB  - Rat germ cells express a 0.9-kilobase (kb) message with a sequence similar to
      that of the 3' portion of mammalian transferrins. The sequence of this
      transcript, called hemiferrin, was considered unique, suggesting that it was
      encoded by a gene different from that of rat transferrin. Difficulties in
      conducting experiments using hemiferrin sequence primers led us to question the
      original sequence. Ribonuclease protection assays revealed that the hemiferrin
      sequence provided protection only for bovine sequences and not for rat mRNA.
      Conversely, a 3' rat transferrin sequence protected only rat liver and testis RNA
      sequences and not bovine sequences, indicating that the 0.9-kb transcript in germ
      cells is a truncated form of rat transferrin. Western analysis and
      immunoprecipitation of germ cell proteins metabolically radiolabeled in vitro and
      in vivo failed to detect a protein of the predicted size regardless of whether
      anti-rat transferrin or anti-hemiferrin antibodies were used. The findings
      suggest that a foreshortened transcript of the transferrin gene is produced in
      rat germ cells and that little or no protein is made from that transcript.

PMID- 12193402
TI  - Circulating leptin concentrations are positively related to leptin messenger RNA
      expression in the adipose tissue of fetal sheep in the pregnant ewe fed at or
      below maintenance energy requirements during late gestation.
AB  - We have investigated the effects of maternal undernutrition during late gestation
      on maternal and fetal plasma concentrations of leptin and on leptin gene
      expression in fetal perirenal adipose tissue. Pregnant ewes were randomly
      assigned at 115 days of gestation (term = 147 +/- 3 days [mean +/- SEM]) to
      either a control group (n = 13) or an undernourished group (n = 16) that received
      approximately 50% of the control diet until 144-147 days of gestation. Maternal
      plasma glucose, but not leptin, concentrations were lower in the undernourished
      ewes. A significant correlation was found, however, between mean maternal plasma
      leptin (y) and glucose (x) concentrations (y = 2.9x - 2.4; r = 0.51, P < 0.02)
      when the control and undernourished groups were combined. Fetal plasma glucose
      and insulin, but not fetal leptin, concentrations were lower in the
      undernourished ewes, and no correlation was found between mean fetal leptin
      concentrations and either mean fetal glucose or insulin concentrations. A
      positive relationship, however, was found between mean fetal (y) and maternal (x)
      plasma leptin concentrations (y = 0.18x + 0.45; r = 0.66, P < 0.003). No
      significant difference was found in the relative abundance of leptin mRNA in
      fetal perirenal fat between the undernourished (0.60 +/- 0.09, n = 10) and
      control (0.70 +/- 0.08, n = 10) groups. Fetal plasma concentrations of leptin (y)
      and leptin mRNA levels (x) in perirenal adipose tissue were significantly
      correlated (y = 1.5x +/- 0.3; r = 0.69, P < 0.05). In summary, the capacity of
      leptin to act as a signal of moderate maternal undernutrition may be limited
      before birth in the sheep.

PMID- 12193401
TI  - Regulation of steroidogenic genes by insulin-like growth factor-1 and follicle
      stimulating hormone: differential responses of cytochrome P450 side-chain
      cleavage, steroidogenic acute regulatory protein, and 3beta-hydroxysteroid
      dehydrogenase/isomerase in rat granulosa cells.
AB  - The present study sought to characterize the concerted action of FSH and insulin
      like growth factor-1 (IGF-1) on functional differentiation of prepubertal rat
      ovarian granulosa cells in culture. To this end, we examined the regulation of
      three key genes encoding pivotal proteins required for progesterone biosynthesis,
      namely, side-chain cleavage cytochrome P450 (P450(scc)), steroidogenic acute
      regulatory (StAR) protein, and 3beta-hydroxysteroid dehydrogenase/isomerase
      (3beta-HSD). Time-dependent expression profiles showed that P450(scc), StAR, and
      3beta-HSD gene products accumulate in chronic, acute, and constitutive patterns,
      respectively. Each of these genes responded to FSH and/or IGF-1 in a
      characteristic manner: A synergistic action of IGF-1 was indispensable for FSH
      induction of P450(scc) mRNA and protein; IGF-1 did not affect FSH-mediated
      upregulation of StAR products; and IGF-1 alone was enough to promote expression
      of 3beta-HSD. The responsiveness of the genes to IGF-1 correlated well with their
      apparent susceptibility to the inhibitory impact of tyrphostin AG18, a potent
      inhibitor of protein tyrosine kinase receptors. Thus, IGF-1-dependent P450(scc)
      and 3beta-HSD expression was completely arrested in the presence of AG18, whereas
      StAR expression was unaffected in the presence of tyrphostin. These findings
      suggest that FSH/cAMP signaling and IGF-1/tyrosine phosphorylation events are
      interwoven in rat ovarian cells undergoing functional differentiation. We also
      sought the mechanism of IGF-1 synergy with FSH. In this regard, our studies were
      unable to demonstrate a stabilizing effect of IGF-1 on P450(scc) mRNA, nor could
      IGF-1 augment FSH-induced transcription examined using a proximal region of the
      P450(scc) promoter (-379/+6). Thus, the mechanism of IGF-1 and FSH synergy
      remains enigmatic and provides a major challenge for future studies.

PMID- 12193403
TI  - Identification of a novel testis-specific member of the phosphatidylethanolamine
      binding protein family, pebp-2.
AB  - The phosphatidylethanolamine binding proteins (pebps) are an evolutionarily
      conserved family of proteins recently implicated in mitogen-activated protein
      (MAP) kinase pathway regulation, where they are called raf kinase inhibitory
      proteins. Here, we describe the cloning, cellular localization, and partial
      characterization of a new member, pebp-2, with potential roles in male fertility.
      Expression data show that pebp-2 is a testis-specific 21-kDa protein found within
      late meiotic and haploid germ cells in a stage-specific pattern that is
      temporally distinct from that of pebp-1. Sequence analyses suggest that pebp-2
      forms a distinct subset of the pebp family within mammals. Database analyses
      revealed the existence of a third subset. Analysis suggests that the
      specificity/regulation of the distinct pebps subsets is likely to be determined
      by the amino terminal 40 amino acids or the 3' untranslated region, where the
      majority of sequence differences occur. Protein homology modeling suggests that
      pebp-2 protein is, however, topologically similar to other pebps and composed of
      Greek key fold motifs, a dominant beta-sheet formed from five anti-parallel beta
      strands forming a shallow groove associated with a putative
      phosphatidylethanolamine binding site. The pebp-2 gene is intronless and data
      suggest that it is a retrogene derived from pebp-1. Further, pebp-2 colocalizes
      with members of the MAP kinase pathway in late spermatocytes and spermatids and
      on the midpiece of epididymal sperm. These data raise the possibility that pebp-2
      is a novel participant in the MAP kinase signaling pathway, with a role in
      spermatogenesis or posttesticular sperm maturation.

PMID- 12193404
TI  - Germinal vesicle material is essential for nucleus remodeling after nuclear
      transfer.
AB  - Successful cloning by nuclear transfer has been reported with somatic or
      embryonic stem (ES) cell nucleus injection into enucleated mouse metaphase II
      oocytes. In this study, we enucleated mouse oocytes at the germinal vesicle (GV)
      or pro-metaphase I (pro-MI) stage and cultured the cytoplasm to the MII stage.
      Nuclei from cells of the R1 ES cell line were injected into both types of
      cytoplasm to evaluate developmental potential of resulting embryos compared to
      MII cytoplasmic injection. Immunocytochemical staining revealed that a spindle
      started to organize 30 min after nucleus injection into all three types of
      cytoplasm. A well-organized bipolar spindle resembling an MII spindle was present
      in both pro-MI and MII cytoplasm 1 h after injection with ES cells. However, in
      the mature GV cytoplasm, chromosomes were distributed throughout the cytoplasm
      and a much bigger spindle was formed. Pseudopronucleus formation was observed in
      pro-MI and MII cytoplasm after activation treatment. Although no pronucleus
      formation was found in GV cytoplasm, chromosomes segregated into two groups in
      response to activation. Only 8.1% of reconstructed embryos with pro-MI cytoplasm
      developed to the morula stage after culture in CZB medium. In contrast, 53.5% of
      embryos reconstructed with MII cytoplasm developed to the morula/blastocyst
      stage, and 5.3% of transferred embryos developed to term. These results indicate
      that GV material is essential for nucleus remodeling after nuclear transfer.

PMID- 12193405
TI  - Lysophosphatidic acid-induced nuclear localization of protein kinase C delta in
      bovine theca cells stimulated with luteinizing hormone.
AB  - The amounts of lysophospholipase D (LPLD) and the ovarian protein kinase C delta
      (PKCdelta) increase during the course of pregnancy. Because LPLD is involved in
      the production of the bioactive phospholipid lysophosphatidic acid (LPA), we
      examined whether stimulation with LPA would influence PKCdelta in the ovary. We
      used immunoblotting and immunohistochemical methods to show that stimulation of
      bovine theca cells with LPA leads to an unexpected redistribution of PKCdelta
      from the cytosol to the perinuclear area and that in the presence of LH, LPA
      induces a complete nuclear translocation of PKCdelta. These effects of LPA are
      dose dependent, can be mimicked by phorbol ester, and are inhibited by a PKCdelta
      inhibitor, rottlerin. Concomitantly, under the same experimental conditions both
      LPA and the phorbol ester PMA (4beta-phorbol-12-myristate-13-acetate) augment LH
      stimulated progesterone accumulation in this cell system. This functional effect
      of LPA and PMA is abolished in cells pretreated with rottlerin. It is unclear
      whether the nuclear localization of PKCdelta indicates a specific function of the
      enzyme in the bovine ovary. Because PKCdelta supports a luteotropic function in
      rodent models, a similar role in the bovine ovary is also likely.

PMID- 12193406
TI  - Gap junctions with varied permeability properties establish cell-type specific
      communication pathways in the rat seminiferous epithelium.
AB  - Dye coupling experiments were performed to determine whether the gap junctions
      connecting Sertoli cells with other Sertoli cells and different germ cell stages
      in rats showed functional variations. Chop loading of adult rat seminiferous
      tubules was conducted using fluorescent dextran controls and a variety of low
      molecular-weight tracers (lucifer yellow, biotin-X-cadaverine, biotin cadaverine,
      and neurobiotin) to evaluate dye coupling in situ, and scrape loading was used to
      study dye coupling in Sertoli-germ cell cocultures established using prepuberal
      rats. Sertoli-Sertoli coupling is relatively short range and nonselective in
      situ, whereas coupling between Sertoli cells and chains of spermatogonia is
      strongly selective for the positively charged biotin tracers relative to
      negatively charged lucifer yellow. Coupling between Sertoli cells and
      spermatogonia was also asymmetric; lucifer yellow in germ cells never diffused
      into Sertoli cells, and biotinylated tracers only weakly diffused from
      spermatogonia to Sertoli cells. Asymmetric coupling would facilitate the
      concentration in germ cells of molecules diffusing through junctions from Sertoli
      cells. Dye coupling between Sertoli cells and adluminal germ cells was too weak
      to detect by fluorescence microscopy, suggesting that the junctional
      communication between these cells may be functionally different from that between
      Sertoli and basal germ cells. The results show that there are multiple routes of
      gap junction communication in rat seminiferous tubules that differ in
      permeability properties and show alternative gating states. Functional diversity
      of gap junctions may permit regulated communication among the many interacting
      Sertoli cells and germ cell stages in the seminiferous epithelium.

PMID- 12193407
TI  - Identification of genes encoding mouse oocyte secretory and transmembrane
      proteins by a signal sequence trap.
AB  - The oocyte plays a key role in follicular development. At all stages of
      follicular development, oocytes interact with surrounding granulosa cells and
      promote their differentiation into the types of cells that support further oocyte
      growth and developmental competence. These interactions suggest the existence of
      an oocyte-granulosa cell regulatory loop that includes both secreted proteins and
      cell surface receptors on both cell types. Factors involved in the regulatory
      loop will therefore contain a signal sequence, which can be used to identify them
      through a signal sequence trap (SST). A screen of an oocyte SST library
      identified three classes of oocyte-expressed sequences: known mouse genes,
      sequences homologous to known mammalian genes, and novel sequences of unknown
      function. Many of the recovered genes may have roles in the oocyte-granulosa cell
      regulatory loop. For several of the known mouse genes, new roles in follicular
      development are implied by identification of their expression, for the first
      time, in the oocyte. The future characterization of novel sequences may lead to
      the identification of novel proteins participating in the regulatory loop.

PMID- 12193409
TI  - Male fertility is linked to the selenoprotein phospholipid hydroperoxide
      glutathione peroxidase.
AB  - The selenoprotein phospholipid hydroperoxide glutathione peroxidase (PHGPx)
      accounts for almost the entire selenium content of mammalian testis. PHGPx is
      abundantly expressed in spermatids as active peroxidase but is transformed to an
      oxidatively inactivated protein in mature sperm, where it is a major constituent
      of the mitochondrial capsule in the midpiece. Male infertility in selenium
      deficient animals, which is characterized by impaired sperm motility and
      morphological midpiece alterations, is considered to result from insufficient
      PHGPx content. We studied the relationship between sperm PHGPx, measured as
      rescued activity, and human fertility. Sperm specimens from 75 infertile men and
      37 controls were analyzed for fertility-related parameters according to World
      Health Organization criteria. The PHGPx protein content was estimated after
      reductive solubilization of the spermatozoa by measuring the rescued PHGPx
      activity. Rescued PHGPx activity of infertile men ranged significantly below that
      of controls (93.2 +/- 60.1 units/mg sperm protein vs. 187.5 +/- 55.3 units/mg)
      and was particularly low in oligoasthenozoospermic specimens (61.93 +/- 45.42
      units/mg; P < 0.001 compared with controls and asthenozoospermic samples).
      Rescued PHGPx activity was correlated positively with viability, morphological
      integrity, and most profoundly forward motility (r = 0.35, 0.44, and 0.45,
      respectively). In isolated motile samples, motility decreased faster with
      decreasing PHGPx content. In humans, PHGPx appears to be indispensable for
      structural integrity of spermatozoa and to codetermine sperm motility and
      viability. Because the content of PHGPx, irrespective of the cause of alteration,
      is correlated with fertility-related parameters, PHGPx can be considered a
      predictive measure for fertilization capacity.

PMID- 12193408
TI  - Altering fish embryos with aquaporin-3: an essential step toward successful
      cryopreservation.
AB  - Fish populations are globally threatened by overharvesting and habitat
      degradation. The ability to bank fish embryos by cryopreservation could be
      crucial for preserving species diversity, for aquaculture (allowing circannual
      fish farming), and for managing fish models used in human biomedical research.
      However, no nonmammalian embryo has ever been successfully cryopreserved. For
      fish, low membrane permeability prevents cryoprotectants from entering the yolk
      to prevent cryodamage. Here, we present evidence of a membrane mechanism
      hindering cryopreservation of fish and propose a novel solution to this obstacle.
      Zebrafish (Danio rerio) embryos have rectifying membranes that allow water to
      leave but not to reenter readily. This feature may be an evolutionary trait that
      allows freshwater embryos to grow in hypoosmotic environments without
      osmoregulatory organs. However, this trait may also prevent successful fish
      embryo cryopreservation because both water and cryoprotectants must move into and
      out of cells. As a solution, we injected zebrafish embryos with mRNA for the
      aquaporin-3 water channel protein and demonstrated increased membrane
      permeability to water and to a cryoprotectant. Modeling indicates that sufficient
      cryoprotectant enters aquaporin-3-expressing zebrafish embryos to allow
      cryopreservation.

PMID- 12193410
TI  - An activator protein-1 complex mediates epidermal growth factor regulation of
      equine glycoprotein alpha subunit expression in trophoblast cells.
AB  - Equids and primates are the only species known to express the placental hormone
      chorionic gonadotropin (CG). CG is a member of the heterodimeric glycoprotein
      family and is composed of an alpha subunit linked to a hormone-specific beta
      subunit. Previously, we have reported that epidermal growth factor (EGF)
      regulates the equine glycoprotein hormone alpha subunit promoter through a
      protein kinase C (PKC)/mitogen-activated protein kinase (MAPK) signal
      transduction pathway in trophoblasts. The current study investigates the
      regulatory element/factors involved in the induction of equine glycoprotein alpha
      subunit gene expression by EGF. Using 5' deletion mutagenesis, we have delineated
      the primary EGF/PKC responsive region of the equine alpha subunit gene to be
      located between -2039 to -2032 base pairs upstream of the transcriptional start
      site. The sequence within this region contains an activator protein 1 (AP-1)-like
      response element (TGAATCA) and is similar to a consensus AP-1 (TGAC/GTCA)
      response element. This element appeared to preferentially interact with a c
      fos/JunD heterodimer. Stimulation by EGF induced the binding of c-fos and JunD to
      this element and subsequently elevated promoter activity. In conclusion, an
      EGF/PKC/MAPK signal transduction pathway regulates equine glycoprotein alpha
      subunit gene expression through a distinct regulatory element(s) that lies
      between -2039 to -2032 of the equine glycoprotein alpha subunit promoter in
      trophoblasts and involves an AP-1 complex.

PMID- 12193411
TI  - A-kinase anchor proteins as potential regulators of protein kinase A function in
      oocytes.
AB  - In the mammalian oocyte, the cAMP-dependent protein kinase (PKA) has critical
      functions in the maintenance of meiotic arrest and oocyte maturation. Because PKA
      is spatially regulated, its localization was examined in developing oocytes. Both
      regulatory subunits (RI and RII) and the catalytic subunit (C) of PKA were found
      in oocytes and metaphase II-arrested eggs. In the oocyte, RI and C were
      predominantly localized in the cortical region, while RII showed a punctate
      distribution within the cytoplasm. After maturation to metaphase II, RI remained
      in the cortex and was also localized to the meiotic spindle, while RII was found
      adjacent to the spindle. C was diffuse within the cytoplasm of the egg but was
      enriched in the cytoplasm surrounding the metaphase spindle, much like RII. The
      polarized localization and redistribution of RI, RII, and C suggested that PKA
      might be tethered by A-kinase anchor proteins (AKAPs), proteins that tether PKA
      close to its physiological substrates. An AKAP, AKAP140, was identified that was
      developmentally regulated and phosphorylated in oocytes and eggs. AKAP140 was
      shown to be a dual-specific AKAP, having the ability to bind both RI and RII. By
      compartmentalizing PKA, AKAP140 and/or other AKAPs could spatially regulate PKA
      activity during oocyte development.

PMID- 12193412
TI  - Multiple Trp isoforms implicated in capacitative calcium entry are expressed in
      human pregnant myometrium and myometrial cells.
AB  - Capacitative Ca2+ entry plays a role in thapsigargin- and oxytocin-mediated
      increases in intracellular free Ca2+ in human myometrium. Members of the Trp
      protein family have been implicated in capacitative Ca2+ entry in a number of
      tissues. Pregnant human myometrium and the human myometrial cell line PHM1-41
      expressed mRNA for hTrp1, hTrp3, hTrp4, hTrp6, and hTrp7. A number of known
      splice variants of hTrp1 and hTrp4 were expressed in these cells. In addition,
      novel splice variants for hTrp1 and hTrp3 were discovered. hTrp1gamma1 and
      hTrp1gamma2 contain insertions between previously described exons 9 and 10 that
      would alter reading frame and produce Trp proteins truncated in the membrane
      spanning region if expressed. The hTrp3 variant introduces sequence between exons
      8 and 9 that would insert 16 amino acids in the C-terminal region of the protein
      upstream of the calmodulin and inositol 1,4,5-triphosphate receptor interaction
      domain. hTrp1, hTrp3, and hTrp4 proteins were detected in both pregnant human
      myometrial and PHM1-41 membranes; a weak band consistent with hTrp6 expression
      was detected in pregnant human myometrium. These data are consistent with the
      presence of proteins that could form putative capacitative Ca2+ channels in human
      myometrium. Control of the activity of these channels may be important for the
      control of uterine contractile activity.

PMID- 12193414
TI  - Regulation of granulosa cell-derived insulin-like growth factor binding proteins
      (IGFBPs): role for protein kinase-C in the pre- and posttranslational modulation
      of IGFBP-4 and IGFBP-5.
AB  - A growing body of information suggests antigonadotropic and atretogenic roles for
      granulosa cell-derived insulin-like growth factor binding proteins (IGFBPs) 4 and
      5 during ovarian folliculogenesis. Activation of protein kinase-A (PKA) in rat
      granulosa cells has been shown to modulate the relative expression of IGFBP-4 and
      -5 transcripts and proteins. In this article, we assess the role of protein
      kinase-C (PKC) in this regard. Provision of granulosa cells with phorbol 12
      myristate 13-acetate (PMA) (but not 4alphaPMA, an inert analogue), a tumor
      promoting phorbol ester and an established activator of PKC, was without
      significant effect on the expression of IGFBP-4 transcripts but resulted in
      biphasic dose-dependent alterations in IGFBP-5 transcripts and in the
      accumulation of the IGFBP-4 and -5 proteins. Comparable effects were noted for
      GnRH, an established PKC agonist. Provision of staurosporine, a potent inhibitor
      of the catalytic subunit of PKC, produced significant dose-dependent decrements
      in the relative expression of IGFBP-5 transcripts. Treatment with FSH
      (presumptively PKA-mediated) markedly attenuated the ability of PMA or GnRH to
      upregulate the accumulation of the IGFBP-5 (but not IGFBP-4) protein. Taken
      together, our present findings indicate that the modulation of rat ovarian IGFBP
      4 and -5 is PKC as well as PKA dependent and that these two signaling pathways
      interact in a diametrically opposed and antagonistic fashion.

PMID- 12193413
TI  - Stimulation of hypoxia-inducible factor-1 alpha (HIF-1alpha) protein in the adult
      rat testis following ischemic injury occurs without an increase in HIF-1alpha
      messenger RNA expression.
AB  - Hypoxia-inducible factor 1 (HIF-1) is a transcription factor composed of alpha
      and beta subunits. Stabilized from proteasome degradation and activated by
      hypoxia, HIF-1 stimulates expression of hypoxia-sensitive genes that mediate
      oxygen homeostasis in many tissues. Our hypothesis is that HIF-1 is involved in
      the cellular response to hypoxia in the ischemic testis. Goals of this study were
      to determine if HIF-1alpha mRNA is expressed in the testis, epididymis, and
      accessory sex glands of adult Sprague-Dawley rats and to determine if HIF-1alpha
      mRNA and protein expression in the testis is affected by experimentally induced
      ischemia. Total RNA from reproductive organs of adult rats was analyzed by
      relative reverse transcription-polymerase chain reaction (RT-PCR) analysis. HIF
      1alpha mRNA showed equal expression in testis, all segments of epididymis, ductus
      deferens, accessory sex glands, and penis. To examine the effects of ischemia on
      HIF-1alpha mRNA and protein expression in the testis, rats were subjected to
      unilateral testicular ischemia by placing a ligature around spermatic artery or
      ischemia-inducing experimental torsion and reperfusion. RT-PCR revealed that HIF
      1alpha mRNA expression at all times of ischemic treatment and reperfusion was
      unchanged compared with normoxic controls. HIF-1alpha protein was detected by
      immunoblot analysis of nuclear protein extracts from normoxic testes. Steady
      state levels of HIF-1alpha protein were stimulated by 15 min of ischemia and
      showed a 2-fold increase at 30 min and 1, 3, and 6 h. HIF-1alpha protein was also
      elevated by experimental torsion and reperfusion compared with normoxic controls.
      These results support the hypothesis that HIF-1 may play a role in the cellular
      response to hypoxia in the ischemic testis.

PMID- 12193415
TI  - Functional and histochemical characterization of a uterine adrenergic denervation
      process in pregnant rats.
AB  - The time course of pregnancy-induced changes in the contractile responses of
      isolated uterine rings and sympathetic innervation pattern were studied using
      electric field stimulation and histofluorescence techniques, respectively, in
      intact and 6-hydroxydopamine-treated rats. Neurally mediated contractions
      elicited by field stimulation (0.6 msec, 1-70 Hz, 40 V) were measured in uterine
      preparations obtained from nonpregnant, 6-hydroxydopamine-treated and 5-, 10-, 15
      , 18-, and 22-day (term) pregnant rats. At all frequencies, the amplitudes of
      contractions were highest in nonpregnant uteri. Stimulation at 1-2.5 Hz evoked
      contractions in 10-day pregnant uteri but failed to cause contractions on Day 5
      and from Day 15 onward. In uterine preparations obtained from term and from 6
      hydroxydopamine-treated rats, contractions could not be evoked by stimulation at
      1-20 Hz. Fluorescence histochemistry of uterine adrenergic nerves revealed rich
      perivascular and myometrial innervation in nonpregnant and in pregnant rats
      through Day 10. Degeneration and loss of adrenergic nerve fibers was apparent by
      Day 15, and fluorescent myometrial and perivascular nerves were practically
      absent by Day 22. These findings demonstrate a progressive, frequency-related
      reduction of nerve-mediated uterine contractions beginning in midterm pregnancy,
      in parallel with a gradual loss of adrenergic nerve fibers. Pregnancy-induced
      nerve degeneration may promote the development of nonsynaptic alpha-adrenergic
      uterine contractile activity towards term. The reduced responsiveness of uterine
      smooth muscle to electric field stimulation in early pregnancy appears to be
      unrelated to alterations in uterine innervation but may be related to changes
      associated with implantation.

PMID- 12193417
TI  - Placental and fetal growth and development in late rat gestation is dependent on
      adrenomedullin.
AB  - Adrenomedullin is a potent, endogenous vasodilator peptide synthesized and
      secreted by diverse locations such as adrenal glands, lungs, kidneys, vascular
      smooth muscle, and endothelium. Homozygous deletion of the adrenomedullin gene is
      embryonic lethal. We hypothesized that adrenomedullin has an important role in
      placental and fetal growth and development in rat pregnancy. The current study
      evaluated maternal systolic blood pressure, litter size, placental and pup
      weight, pup mortality, and placental pathology in pregnant rats following
      continuous in utero exposure to an adrenomedullin antagonist. Osmotic minipumps
      were inserted on Gestational Day 14 to continuously deliver either
      adrenomedullin, adrenomedullin antagonist, or vehicle control. Systolic blood
      pressure was recorded daily. Pregnant rats were killed on Gestational Day 15-18,
      20, and/or 22 to evaluate placental development and fetal growth. The placentas
      were graded for the presence of necrosis in the decidua and fetal labyrinth as
      well as fetal vessel development in the labyrinth. A trend toward increased
      systolic blood pressure was noted between Gestational Days 17 and 20 in mothers
      treated with adrenomedullin antagonist, but the difference was not statistically
      significant. Antagonism of adrenomedullin function during rat pregnancy caused
      fetal growth restriction, decreased placental size, gross necrosis of placental
      margins and amniotic membranes, histologically deficient fetal vessel development
      in the labyrinth, and fetal edema. Adrenomedullin contributes to angiogenesis,
      functions as a growth factor, and helps regulate vascular tone during rat
      gestation.

PMID- 12193416
TI  - Growth and differentiation factor-9 stimulates progression of early primary but
      not primordial rat ovarian follicle development.
AB  - The ovary contains a pool of primordial follicles containing oocytes arrested in
      meiosis that are the source of developing follicles for the female. Growth and
      differentiation factor-9 (GDF-9) is a member of the transforming growth factor
      beta superfamily of growth factors, and follicles of GDF-9 knockout mice arrest
      in the primary stage of development. The effect of GDF-9 treatment on the
      primordial to primary follicle transition and on subsequent follicle progression
      was examined using a rat ovary organ culture system. Ovaries from 4-day-old rats
      were cultured under serum-free conditions in the absence or presence of growth
      factors. GDF-9 treatment caused a decrease in the proportion of stage 1 early
      primary follicles and a concomitant increase in the proportion of stage 2 mature
      primary follicles. GDF-9 did not effect primordial follicles or stage 0 to stage
      1 follicle transition. GDF-9 also did not influence stage 3 or 4 secondary
      follicle numbers. Isolated antral follicle granulosa and theca cell cultures were
      used to analyze the actions of GDF-9. GDF-9 treatment did not directly influence
      either granulosa or theca cell proliferation. The ability of GDF-9 to influence
      the expression of another growth factor was examined. GDF-9 treatment increased
      kit ligand (KL) mRNA expression in bovine granulosa cells after 2 days of
      culture. Ovaries from 4-day-old rats were also cultured with or without GDF-9
      treatment, and total ovary expression of KL mRNA was increased by GDF-9. In
      summary, GDF-9 was found to promote the progression of early primary follicle
      development but did not influence primordial follicle development. The actions of
      GDF-9 on specific stages of follicle development may in part be mediated through
      altering the expression of KL.

PMID- 12193418
TI  - Are paediatricians failing at school?

PMID- 12193419
TI  - Health services: who are the best advocates for children?

PMID- 12193420
TI  - Advances in the prevention and treatment of paediatric HIV infection in the
      United Kingdom.

PMID- 12193421
TI  - The role of lumbar puncture in suspected CNS infection--a disappearing skill?

PMID- 12193422
TI  - The treatment of parental height as a biological factor in studies of birth
      weight and childhood growth.
AB  - Parental height is frequently treated as a biological variable in studies of
      birth weight and childhood growth. Elimination of social variables from
      multivariate models including parental height as a biological variable leads
      researchers to conclude that social factors have no independent effect on the
      outcome. This paper challenges the treatment of parental height as a biological
      variable, drawing on extensive evidence for the determination of adult height
      through a complex interaction of genetic and social factors. The paper firstly
      seeks to establish the importance of social factors in the determination of
      height. The methodological problems associated with treatment of parental height
      as a purely biological variable are then discussed, illustrated by data from
      published studies and by analysis of data from the 1958 National Childhood
      Development Study (NCDS). The paper concludes that a framework for studying
      pathways to pregnancy and childhood outcomes needs to take account of the
      complexity of the relation between genetic and social factors and be able to
      account for the effects of multiple risk factors acting cumulatively across time
      and across generations. Illustrations of these approaches are given using NCDS
      data.

PMID- 12193423
TI  - A visual motor psychological test as a predictor to treatment in nocturnal
      enuresis.
AB  - BACKGROUND AND AIMS: The neurological control of bladder function and the ability
      to be dry at night involves not only the acquisition of normal daytime control,
      but also the establishment of a circadian rhythm in vasopressin release and the
      ability to arouse to a full bladder during sleep. We postulated that in some
      children there might be a delay in maturation of the normal neurological pathways
      involved in establishment of nocturnal continence and examined this by using a
      specific neuropsychological test. METHODS: Children attending an established
      nocturnal enuresis clinic were examined using the Rey-Osterrieth test to assess
      the presence or absence of boundary errors in both copy and memory reproductions.
      The results of the test were scored independently and blind to the response to
      treatment with the vasopressin analogue DDAVP. RESULTS: A significant association
      was found between boundary type errors and response to DDAVP, with non-responders
      making significantly more errors. No child with three or more errors responded to
      DDAVP. Using this test, the ability to predict response to treatment was 70%.
      CONCLUSIONS: It is postulated that the Rey-Osterrieth test, through the presence
      or absence of boundary errors, reflects a delay in maturation and/or a
      disorganisation of the retinal-hypothalamic-cortical pathways in the brain. The
      association previously described with growth hormone neurosecretory dysfunction
      syndrome would be compatible with this.

PMID- 12193425
TI  - Ventriculoperitoneal shunt block: what are the best predictive clinical
      indicators?
AB  - AIMS: To evaluate the predictive value of symptoms, signs, and radiographic
      findings accompanying presumed ventriculoperitoneal (VP) shunt malfunction, by
      comparing presentation with operative findings and subsequent clinical course.
      METHODS: Prospective study of all 53 patient referrals to a paediatric
      neurosurgical centre between April and November 1999 with a diagnosis of presumed
      shunt malfunction. Referral pattern, presenting symptoms and signs, results of
      computed tomography (CT) scanning, operative findings, and clinical outcome were
      recorded. Two patient groups were defined, one with proven shunt block, the other
      with presumed normal shunt function. Symptomatology, CT scan findings, and the
      subsequent clinical course for each group were then compared. RESULTS: Common
      presenting features were headache, drowsiness, and vomiting. CT scans were
      performed in all patients. Thirty seven had operatively proven shunt malfunction,
      of whom 34 had shunt block and three shunt infection; 84% with shunt block had
      increased ventricle size when compared with previous imaging. For the two patient
      groups (with and without shunt block), odds ratios with 95% confidence intervals
      on their presenting symptoms were headache 1.5 (0.27 to 10.9), vomiting 0.9 (0.25
      to 3.65), drowsiness 10 (0.69 to 10.7), and fever 0.19 (0.03 to 6.95). Every
      patient with ventricular enlargement greater than their known baseline had a
      proven blocked shunt. CONCLUSIONS: Drowsiness is by far the best clinical
      predictor of VP shunt block. Headache and vomiting were less predictive of acute
      shunt block in this study. Wherever possible CT scan findings should be
      interpreted in the context of previous imaging. We would caution that not all
      cases of proven shunt blockage present with an increase in ventricle size.

PMID- 12193424
TI  - Leptin, malnutrition, and immune response in rural Gambian children.
AB  - BACKGROUND: The adipocyte derived hormone, leptin, has cytokine like function and
      may mediate the effects of starvation on immunity. Mice with congenital leptin
      deficiency (ob/ob) have small hypocellular thymuses and impaired cellular
      immunity. In humans leptin influences the differentiation of naive and memory
      cells in vitro, and genetic leptin deficiency has been associated with an ill
      defined susceptibility to infection. AIMS: To describe the in vivo relation of
      leptin and immune function in children. METHODS: Fasting plasma leptin
      concentrations, immune function (T and B cell mediated vaccine responses and
      delayed type hypersensitivity), and mucosal function (dual sugar permeability
      test and salivary sIgA concentrations) were measured in a cohort of 472
      moderately undernourished rural Gambian children. RESULTS: Leptin concentrations
      correlated with body fat assessed by mid upper arm circumference or BMI for age Z
      scores, and were very low compared to well nourished European norms (males 1.8 v
      11.1 ng/ml; females 2.4 v 13.8 ng/ml). No detectable relations were found between
      leptin concentrations and any of the measures of immune or mucosal function.
      CONCLUSIONS: The data confirm that leptin acts as a peripheral signal of energy
      restriction, but do not support an association between fasting plasma leptin
      levels and immune function in children of this age.

PMID- 12193426
TI  - Causes of morbilliform rash in a highly immunised English population.
AB  - AIMS: To determine the causes of morbilliform rash and fever in a population with
      high vaccination coverage for measles and rubella. METHODS: Comprehensive
      laboratory investigation additional to routine oral fluid testing of children
      presenting to primary care physicians in East Anglia, England. RESULTS:
      Laboratory confirmation of infection was obtained in 93 (48%) of 195 children:
      parvovirus B19 in 34 (17%); group A streptococcus in 30 (15%); human herpesvirus
      type 6 in 11 (6%); enterovirus in nine (5%); adenovirus in seven (4%); and group
      C streptococcus in six (3%) (four individuals tested positive for two agents).
      None had measles or rubella. CONCLUSIONS: Oral fluid testing to cover infections
      additional to measles and rubella aids clinical management and is likely to
      maintain uptake of testing, which is essential for measles and rubella
      surveillance in highly immunised low incidence populations.

PMID- 12193427
TI  - The emergence of resistant pneumococcal meningitis--implications for empiric
      therapy.
AB  - BACKGROUND: Following the emergence of penicillin and cephalosporin resistant
      pneumococcal meningitis in the United States, inclusion of vancomycin in empiric
      therapy for all suspected bacterial meningitis was recommended by the American
      Academy of Pediatrics. Few data are available to evaluate this policy. AIMS: To
      examine the management and clinical course in relation to antibiotic therapy of a
      large unselected cohort of children with pneumococcal meningitis in a geographic
      area where antibiotic resistance has recently increased. METHODS: Retrospective
      review of all cases of pneumococcal meningitis in a defined population (Sydney,
      Australia), 1994-99. RESULTS: A total of 104 cases without predisposing illnesses
      were identified; timing of lumbar puncture (LP) was known in 103. Resistance to
      penicillin increased from 0 to 20% over the study period. Only 57 (55%) had an
      early LP (prior to parenteral antibiotics); 55 (96%) had organisms on Gram stain.
      Severe disease (intensive care admission or death) increased significantly from
      57 cases with early LP (28%) to 33 with delayed LP (42%) to 13 with no LP (62%).
      Evidence of pneumococcal infection was available within 24 hours in 85% of those
      with delayed or no LP. Outcome was not related to empiric vancomycin use, which
      increased from 5% prior to 1998 to 48% in 1999. CONCLUSION: LP is frequently
      delayed in pneumococcal meningitis. Based on disease severity, empiric vancomycin
      is most justified when LP is deferred. If an early LP is done, vancomycin can be
      withheld if Gram positive diplococci are not seen.

PMID- 12193429
TI  - The impact of human immunodeficency virus 1 on largyngeal airway obstruction in
      children.
AB  - Children with laryngeal airway obstruction (LAO) require admission to the
      intensive care unit (ICU). The unresolved ethical dilemma of ICU access for HIV
      infected children in resource poor settings requires further scientific data to
      help guide triaging. Of 38 children with LAO, 19 had HIV infection. The
      mortality, need for supportive management, duration of intubation, intermittent
      positive pressure ventilation, and ICU and hospitalisation stay were similar in
      the HIV infected group compared to the HIV uninfected group. Episodes of
      laryngotracheobronchitis were equally distributed between both groups (31.6% v
      31.3%), while oropharyngeal/laryngeal candidiasis (26.3%), tuberculosis (15.8%),
      and benign lymphoid hyperplasia (15.8%) were commonly seen in the HIV infected
      group.

PMID- 12193430
TI  - High dose growth hormone treatment induces acceleration of skeletal maturation
      and an earlier onset of puberty in children with idiopathic short stature.
AB  - BACKGROUND: Long term growth hormone (GH) treatment in children with idiopathic
      short stature (ISS) results in a relatively small mean gain in final height of 3
      9 cm, which may not justify the cost of treatment. As it is unknown whether GH
      treatment during puberty adds to final height gain, we sought to improve the cost
      benefit ratio, employing a study design with high dose GH treatment restricted to
      the prepubertal period. AIMS: To assess the effect of short term, high dose GH
      treatment before puberty on growth, bone maturation, and pubertal onset. METHODS:
      Five year results of a randomised controlled study are reported. Twenty six boys
      and nine girls were randomly assigned to a GH treatment group (n = 17) or a
      control group (n = 18). Inclusion criteria were: no signs of puberty, height less
      than -2 SDS, age 4-8 years for girls or 4-10 years for boys, GH concentration >10
      micro g/l after provocation, and normal body proportions. To assess GH
      responsiveness, children assigned to the GH treatment group received GH treatment
      for two periods of three months (1.5 IU/m2/day and 3.0 IU/m2/day), separated by
      three month washout periods, during the first year of study. High dose GH
      treatment (6.0 IU/m2/day) was then started and continued for at least two full
      years. When puberty occurred, GH treatment was discontinued at the end of a
      complete year's treatment (for example, three or four years of GH treatment).
      RESULTS: In response to at least two years on high dose GH treatment, mean (SD)
      height SDS for chronological age increased significantly in GH treated children
      from -2.6 (0.5) to -1.3 (0.5) after two years and -1.4 (0.5) SDS after five years
      of study. No changes in height SDS were observed in controls. A rapid rate of
      bone maturation of 3.6 years/2 years in treated children compared to 2 years/2
      years in controls was observed in response to two years high dose GH treatment.
      Height SDS for bone age was not significantly different between groups during the
      study period. GH treated children entered into puberty at a significantly earlier
      age compared to controls. CONCLUSIONS: High dose GH treatment before puberty
      accelerates bone age and induces an earlier onset of puberty. This may limit the
      potential therapeutic benefit of this regimen in ISS.

PMID- 12193431
TI  - Controlled study of respiratory viruses and wheezing.

PMID- 12193432
TI  - Idiopathic intracranial hypertension: is papilloedema inevitable?
AB  - Headaches and papilloedema are key features of idiopathic (benign) intracranial
      hypertension (IIH). We describe three children in whom IIH was diagnosed in the
      absence of papilloedema. Recognition of atypical cases of IIH is important
      because pressure lowering treatment may be effective.

PMID- 12193434
TI  - Respiratory depression in the acute management of seizures.
AB  - The incidence of respiratory depression following treatment of prolonged seizures
      with benzodiazepines is variable in the literature. We retrospectively reviewed
      the charts of children treated for prolonged seizure over a one year period. Of
      the 56 seizures treated, 30 received lorazepam, 19 diazepam, and seven both
      drugs. Twenty two episodes (39%) of prolonged seizure were treated with multiple
      doses of benzodiazepines. In eight events (14%), there was documented respiratory
      depression following the administration of one or more doses of benzodiazepine;
      in six of these, multiple doses were given. The doses used were often at the low
      end or less than the recommended dose for treatment of status epilepticus. These
      data support suggestions that multiple doses of benzodiazepines increase the risk
      of respiratory depression.

PMID- 12193435
TI  - Atypical bleeding due to idiopathic thrombocytopenia in association with low
      factor VIII levels.
AB  - Two children with bleeding from idiopathic thrombocytopenia with low factor VIII
      levels are described. The presence of a double haemostatic defect in an otherwise
      healthy individual presenting with bleeding is extremely rare. In both cases the
      atypical bleeding raised the suspicion of dual pathology.

PMID- 12193436
TI  - Erythromelalgia: an endothelial disorder responsive to sodium nitroprusside.
AB  - Erythromelalgia is an unusual syndrome of painful vasodilatation. Aetiopathology
      is probably different in children and adults. Presentation can be severe and
      associated with hypertension. Dramatic benefit from infused nitroprusside
      suggests the disorder could represent a dysfunctional endothelium.

PMID- 12193438
TI  - Treatment with cyclosporin A in a patient with Omenn's syndrome.
AB  - Unless treated with haematopoetic stem cell transplantation, Omenn's syndrome, a
      rare variant of severe combined immunodeficiency, is associated with a fatal
      outcome. We describe a male infant showing all the typical features of Omenn's
      syndrome, who was successfully treated with cyclosporin A to improve clinical
      condition prior to haematopoetic stem cell transplantation.

PMID- 12193439
TI  - Time off.

PMID- 12193440
TI  - When to do a lumbar puncture.

PMID- 12193441
TI  - Lumbar puncture following febrile convulsion.

PMID- 12193443
TI  - Interhospital transport to paediatric intensive care by specialised staff:
      experience of the South Thames combined transport service, 1998-2000.
AB  - The South London Combined Transport Service retrieved 1536 children aged 1 month
      to 16 years to paediatric intensive care (PIC) units usually in south London,
      over a 2.5 year period. Eighty one per cent of cases were for general PIC, the
      specialist cases being mainly cardiac and neurosurgical. The service commenced as
      part of a national framework for improved PIC and offers children with complex
      needs a safe specialist transfer. Clinician and parental satisfaction with the
      service appears high, although there are considerable service pressures.
      Intensive care beds were successfully located, helping to reduce fragmentation of
      PIC for this population.

PMID- 12193442
TI  - Controversies and advances in the management of Wilms' tumour.
AB  - Wilms tumour is one of the success stories of paediatric oncology with long term
      survival approaching 90% in localised disease and over 70% for metastatic
      disease. Although appearing relatively simple compared to other cancer treatment
      regimens, successful treatment of Wilms tumour requires meticulous attention to
      correct staging of the tumour and good communication between the paediatric
      surgeon, pathologist and oncologist. The controversy of whether pre-operative
      chemotherapy results in a reduced overall burden of treatment compared to
      immediate nephrectomy has been addressed by the recently closed UKW3 randomised
      trial. Challenges remain in identification of histological and molecular risk
      factors for stratification of treatment intensity to allow safe reduction in
      therapy and avoidance of late sequelae for the majority while leading to
      increased biological insights and ultimately novel therapies for the minority of
      high risk tumours. Genetic predisposition to Wilms tumour is conferred by several
      genes, some of which cause malformation rather than cancer and may be of low
      penetrance. The proportion of children with heritable disease is uncertain and
      there remains a need to collect data on the need for screening in this
      susceptible population.

PMID- 12193444
TI  - Airway resistance measured by the interrupter technique: normative data for 2-10
      year olds of three ethnicities.
AB  - BACKGROUND AND AIMS: The measurement of airway resistance using the interrupter
      technique (R(int)) is feasible in preschool children and other subjects unable to
      undertake spirometry. This makes it potentially useful for the measurement of
      lung function in these groups. Commercial devices use different algorithms to
      measure pressure and flow from which R(int) is derived. This study provides
      normative values for British children using devices from a single manufacturer.
      METHODS: R(int) was measured in 236 healthy children of three ethnic groups (Afro
      Caribbean and black African, Bangladeshi, and white British) aged 2-10 years
      using Micro Medical devices. Software in the devices calculated R(int) from
      pressure measured by the two point, back extrapolation method from the pressure
      transient during valve closure, with flow measured just before valve closure.
      RESULTS: R(int) is related to both age and height, but when age is allowed for
      there is not a significant relation with height. Neither gender nor any of the
      ethnicities studied was significantly related to R(int). DISCUSSION: These
      measurements in healthy children using this technique may be used as reference
      data for similar populations.

PMID- 12193445
TI  - Phase angle and n-3 polyunsaturated fatty acids in sickle cell disease.
AB  - Phase angle, an impedance parameter used for nutritional assessment, is
      reflective of the capacitance properties of cell membranes. We have shown a
      significant correlation between the proportions of specific n-3 polyunsaturated
      fatty acids in the serum phospholipids of Nigerian children with sickle cell
      disease and their phase angles determined by bioelectrical impedance analysis.

PMID- 12193446
TI  - Lactic dehydrogenase isoenzymes in cerebrospinal fluid of children with Guillain
      Barre syndrome.
AB  - BACKGROUND: Increased levels of lactic dehydrogenase (LDH) in the cerebrospinal
      fluid (CSF) have been reported in association with several intracranial
      pathologies. No studies have been performed on patients with Guillain-Barre
      syndrome (GBS). AIMS: To study LDH isoenzymes in CSF of children with GBS.
      METHODS: CSF samples collected from nine patients with GBS were analysed for
      total LDH isoenzymes activity, and compared to samples from 15 patients with
      normal results. RESULTS: Mean total LDH activity was 33.33 (6.63) U/l. All
      patients had significantly increased LDH-3 isoenzyme compared to controls. LDH-3
      was the predominant fraction, accounting for more than 50% of total LDH activity
      and present in more than twice the percentage of LDH-1 or LDH-2. By contrast, in
      the control group, there were high percentages of mainly LDH-1 and LDH-2.
      CONCLUSIONS: GBS is apparently associated with a distinct LDH isoenzyme pattern
      in the CSF. More studies are needed to confirm the rise in LDH-3, as serial CSF
      analyses are unavailable, and to determine the optimum time of analysis when this
      finding first becomes detectable.

PMID- 12193448
TI  - The ethics of tiny trials.

PMID- 12193447
TI  - Respiratory failure due to pulmonary calcification in primary
      hyperparathyroidism.

PMID- 12193450
TI  - Discontinuing anticonvulsant medication in children.

PMID- 12193451
TI  - Do grommets prevent language delay?

PMID- 12193452
TI  - Is melatonin likely to help children with neurodevelopmental disability and
      chronic severe sleep problems?

PMID- 12193453
TI  - Is perianal dermatitis a sign of sexual abuse?

PMID- 12193455
TI  - Munchausen syndrome involving pets by proxies.

PMID- 12193454
TI  - The prevalence of rickets among non-Caucasian children.

PMID- 12193456
TI  - Paediatricians' misconceptions on childhood immunisations.

PMID- 12193457
TI  - Phosphatidylinositol 3-kinase: a key regulator of vascular tone?

PMID- 12193458
TI  - The Ca2+ synapse redo: a matter of location, location, location.

PMID- 12193459
TI  - Short-term treatment with ranolazine improves mechanical efficiency in dogs with
      chronic heart failure.
AB  - The present study assesses whether ranolazine increases left ventricular (LV)
      function without an increase in myocardial oxygen consumption (MVO2) and thus
      improves LV mechanical efficiency in dogs with heart failure (HF). Ranolazine did
      not change MVO2 and LV mechanical efficiency increased (22.4+/-2.8% to 30.9+/
      3.4% (P<0.05). In contrast, dobutamine significantly increased MVO2 and did not
      improve mechanical efficiency. Thus, short-term treatment with ranolazine
      improved LV function without an increase in MO2, resulting in an increased
      myocardial mechanical efficiency in dogs with HF.

PMID- 12193460
TI  - Innate and adaptive immunity in the pathogenesis of atherosclerosis.
AB  - This review considers critically the evidence for the involvement of mediators of
      innate and acquired immunity in various stages of atherosclerosis. Rapidly
      mobilized arms of innate immunity, including phagocytic leukocytes, complement,
      and proinflammatory cytokines, contribute to atherogenesis. In addition, adaptive
      immunity, with its T cells, antibodies, and immunoregulatory cytokines,
      powerfully modulates disease activity and progression. Atherogenesis involves
      cross talk between and shared pathways involved in adaptive and innate immunity.
      Immune processes can influence the balance between cell proliferation and death,
      between synthetic and degradative processes, and between pro- and antithrombotic
      processes. Various established and emerging risk factors for atherosclerosis
      modulate aspects of immune responses, including lipoproteins and their modified
      products, vasoactive peptides, and infectious agents. As we fill in the molecular
      details, new potential targets for therapies will doubtless emerge.

PMID- 12193461
TI  - Functional compartmentation of endothelial P2Y receptor signaling.
AB  - The presence of multiple receptors for disparate nucleotides on endothelial cells
      makes it unclear how the endothelium differentiates among these signals. We
      propose that endothelial P2Y receptors are organized into cholesterol-rich
      signaling domains, such as caveolae and respond to nucleotide agonists by
      mobilizing intracellular calcium. Treatment of endothelial cells with 5 mmol/L
      beta-methyl-cyclodextrin prevents calcium release in response to the nucleotide
      receptor agonists 2-methylthio-ATP, ATP, ADP, and UTP, but not the kinin receptor
      agonist bradykinin, suggesting that depletion of membrane cholesterol disrupts
      signaling at P2Y receptors and that bradykinin receptors are not prelocalized to
      cholesterol microdomains in these cells. Direct measurement of cholesterol
      content after beta-methyl-cyclodextrin treatment of aortic rings reveals a
      concentration-dependent depletion of cholesterol that parallels functional
      antagonism of P2Y-mediated relaxation. Nucleotide- and bradykinin-mediated
      relaxation is disrupted by 5 to 15 mmol/L beta -methyl-cyclodextrin treatment or
      1 to 10 microg/mL filipin III in a concentration-dependent fashion.
      Norepinephrine contracted aorta treated with A23187 relaxes in an endothelium
      dependent fashion despite depletion of 84% of membrane-extractable cholesterol.
      These data indicate that in the basal state, P2Y receptors but not the kinin
      receptor may be compartmented to cholesterol-dependent signaling domains in
      guinea pig endothelium and that cholesterol-rich microdomains in these cells can
      respond to intracellular calcium in an agonist-specific manner. We suggest that
      the functional organization of cholesterol-rich signaling microdomains allows
      agonist-specific responses to increases in intracellular calcium and that this
      property may be a general phenomenon that permits cells to respond disparately to
      agonists that may signal through common calcium release pathways.

PMID- 12193462
TI  - Chronic hypoxia increases endothelial nitric oxide synthase generation of nitric
      oxide by increasing heat shock protein 90 association and serine phosphorylation.
AB  - Chronic hypoxia increases endothelial nitric oxide synthase (eNOS) production of
      nitric oxide (*NO) and cardioprotection in neonatal rabbit hearts. However, the
      mechanism by which this occurs remains unclear. Recent studies suggest that heat
      shock protein 90 (hsp90) alters eNOS function. In the present study, we examined
      the role of hsp90 in eNOS-dependent cardioprotection in neonatal rabbit hearts.
      Chronic hypoxia increased recovery of postischemic left ventricular developed
      pressure (LVDP). Geldanamycin (GA), which inhibits hsp90 and increases oxidative
      stress, decreased functional recovery in normoxic and hypoxic hearts. To
      determine if a loss in *NO, afforded by GA, decreased recovery, GA-treated hearts
      were perfused with S-nitrosoglutathione (GSNO) as a source of *NO. GSNO increased
      recovery of postischemic LVDP in GA-treated normoxic and hypoxic hearts to
      baseline levels. Although chronic hypoxia decreased phosphorylated eNOS (S1177)
      levels by approximately 4- to 5-fold and total Akt and phosphorylated Akt by 4-
      and 5-fold, it also increased hsp90 association with eNOS by more than 3-fold.
      Using hydroethidine (HEt), a fluorescent probe for superoxide, we found that
      hypoxic hearts contained less ethidine (Et) staining than normoxic hearts.
      Normoxic hearts generated 3 times more superoxide by an N(omega)-nitro-L-arginine
      methyl ester (L-NAME)-inhibitable mechanism than hypoxic hearts. Taken together,
      these data indicate that the association of hsp90 with eNOS is important for
      increasing *NO production and limiting eNOS-dependent superoxide anion
      generation. Such changes in eNOS function appear to play a critical role in
      protecting the myocardium against ischemic injury.

PMID- 12193463
TI  - Functionally novel tumor necrosis factor-alpha-modulated CHR-binding protein
      mediates cyclin A transcriptional repression in vascular endothelial cells.
AB  - Local expression of tumor necrosis factor-alpha (TNF-alpha) at the sites of
      arterial injury after balloon angioplasty, suppresses endothelial cell (EC)
      proliferation and negatively affects reendothelialization of the injured vessel.
      We have previously reported that in vitro exposure of ECs to TNF-alpha induced EC
      growth arrest and apoptosis. These effects were mediated, at least in part, by
      downregulation of cell cycle regulatory proteins. In the present study, we report
      potential mechanism(s) for TNF-alpha-mediated suppression of cyclin A in ECs. TNF
      alpha exposure to ECs completely abrogated cyclin A mRNA expression via
      mechanisms involving both transcriptional and posttranscriptional modifications.
      TNF-alpha inhibited de novo cyclin A mRNA synthesis and suppressed cyclin A
      promoter activity. Utilizing deletion mutants of human cyclin A promoter, we have
      identified CDE-CHR (Cell cycle-Dependent Elements-Cell cycle genes Homology
      Region) region of cyclin A promoter as a target for TNF-alpha suppressive action.
      Experiments to investigate CDE-CHR binding proteins/factors revealed a TNF-alpha
      mediated increase in specific DNA binding activity to the CHR elements. This
      increase in binding activity by TNF-alpha was mediated via the induction of a
      functionally novel 84-kDa protein that binds specifically to CHR in Southwestern
      assays. UV cross-linking and SDS-PAGE analysis of proteins eluted from specific
      complex confirmed the presence of this 84-kDa protein. Moreover, induction of
      this protein by TNF-alpha was protein synthesis dependent. Additionally, exposure
      of ECs to TNF-alpha markedly reduced cyclin A mRNA stability. Targeted disruption
      of this protein could potentially be a therapeutic strategy to rescue EC
      proliferation in vivo.

PMID- 12193464
TI  - Na+-Ca2+ exchange activity is localized in the T-tubules of rat ventricular
      myocytes.
AB  - Detubulation of rat ventricular myocytes has been used to investigate the role of
      the t-tubules in Ca2+ cycling during excitation-contraction coupling in rat
      ventricular myocytes. Ca2+ was monitored using fluo-3 and confocal microscopy. In
      control myocytes, electrical stimulation caused a spatially uniform increase in
      intracellular [Ca2+] across the cell width. After detubulation, [Ca2+] rose
      initially at the cell periphery and then propagated into the center of the cell.
      Application of caffeine to control myocytes resulted in a rapid and uniform
      increase of intracellular [Ca2+]; the distribution and amplitude of this increase
      was the same in detubulated myocytes, although its decline was slower. On
      application of caffeine to control cells, there was a large, rapid, and transient
      rise in extracellular [Ca2+] as Ca2+ was extruded from the cell; this rise was
      significantly smaller in detubulated cells, and the remaining increase was
      blocked by the sarcolemmal Ca2+ ATPase inhibitor carboxyeosin. The treatment used
      to produce detubulation had no significant effect on Ca2+ efflux in atrial cells,
      which lack t-tubules. Detubulation of ventricular myocytes also resulted in loss
      of Na+-Ca2+ exchange current, although the density of the fast Na+ current was
      unaltered. It is concluded that Na+-Ca2+ exchange function, and hence Ca2+ efflux
      by this mechanism, is concentrated in the t-tubules, and that the concentration
      of Ca2+ flux pathways in the t-tubules is important in producing a uniform
      increase in intracellular Ca2+ on stimulation.

PMID- 12193465
TI  - Increased exchange current but normal Ca2+ transport via Na+-Ca2+ exchange during
      cardiac hypertrophy after myocardial infarction.
AB  - Hypertrophied and failing cardiac myocytes generally show alterations in
      intracellular Ca2+ handling associated with changes in the contractile function
      and arrhythmogenicity. The cardiac Na+-Ca2+ exchange (NCX) is an important
      mechanism for Ca2+ extrusion and cell relaxation. Its possible involvement in
      changes of excitation-contraction coupling (EC-coupling) with disease remains
      uncertain. We analyzed the NCX function in rat ventricular myocytes 5 to 6 months
      after experimental myocardial infarction (PMI) produced by left coronary artery
      ligation and from sham-operated (SO) hearts. Caged Ca2+ was dialyzed into the
      cytoplasm via a patch-clamp pipette and Ca2+ was released by flash photolysis to
      activate NCX and measure the associated currents (I(NaCa)), whereas [Ca2+]i
      changes were simultaneously recorded with a confocal microscope. I(NaCa) density
      normalized to the [Ca2+]i jumps was 2.6-fold higher in myocytes from PMI rats.
      The level of total NCX protein expression in PMI myocytes was also increased.
      Interestingly, although the I(NaCa) density in PMI cells was larger, PMI and SO
      myocytes presented virtually identical Ca2+ transport via the NCX. This
      discrepancy was explained by a reduced surface/volume ratio (34.8%) observed in
      PMI cells. We conclude that the increase in NCX density may be a mechanism to
      maintain the required Ca2+ extrusion from a larger cell to allow adequate
      relaxation.

PMID- 12193466
TI  - Cardiac microstructure: implications for electrical propagation and
      defibrillation in the heart.
AB  - Our understanding of the electrophysiological properties of the heart is
      incomplete. We have investigated two issues that are fundamental to advancing
      that understanding. First, there has been widespread debate over the mechanisms
      by which an externally applied shock can influence a sufficient volume of heart
      tissue to terminate cardiac fibrillation. Second, it has been uncertain whether
      cardiac tissue should be viewed as an electrically orthotropic structure, or
      whether its electrical properties are, in fact, isotropic in the plane orthogonal
      to myofiber direction. In the present study, a computer model that incorporates a
      detailed three-dimensional representation of cardiac muscular architecture is
      used to investigate these issues. We describe a bidomain model of electrical
      propagation solved in a discontinuous domain that accurately represents the
      microstructure of a transmural block of rat left ventricle. From analysis of the
      model results, we conclude that (1) the laminar organization of myocytes
      determines unique electrical properties in three microstructurally defined
      directions at any point in the ventricular wall of the heart, and (2)
      interlaminar clefts between layers of cardiomyocytes provide a substrate for bulk
      activation of the ventricles during defibrillation.

PMID- 12193467
TI  - Life span of ventricular fibrillation frequencies.
AB  - The nature and organization of electrical activity during ventricular
      fibrillation (VF) are important and controversial subjects dominated by 2
      competing theories: the wavebreak and the dominant mother rotor hypothesis. To
      investigate spatiotemporal characteristics of ventricular fibrillation (VF),
      transmembrane potentials (V(m)) were recorded from multiple sites of perfused
      rabbit hearts using a voltage-sensitive dye and a photodiode array or a CCD
      camera, and the time-frequency characteristics of V(m) were analyzed by short
      time fast Fourier transform (FFT) or generalized time-frequency representation
      with a cone-shaped kernel. The analysis was applied to all pixels to track VF
      frequencies in time and space. VF consisted of blobs, which are groups of
      contiguous pixels with a common frequency and an ill-defined shape. At any time
      t, several VF frequency blobs coexisted in the field of view, and the number of
      coexisting blobs was on average 5.9+/-2.1 (n=8 hearts) as they appeared and
      disappeared discontinuously with time and were not fixed in space. The life span
      of frequency blobs from birth to either annihilation or breakup to another
      frequency had a half-life of 0.39+/-0.13 second (n=4 hearts). The Ca2+ channel
      blocker nifedipine increased the stability of VF frequencies and reduced the
      number of frequency blobs progressing to a single frequency. In conclusion, VF
      consists of dynamically changing frequency blobs, which have a short life span
      and can be modified by pharmacological interventions, suggesting that VF is
      maintained by dynamically changing multiple wavelets.

PMID- 12193468
TI  - Protease-activated receptor-2 stimulates angiogenesis and accelerates hemodynamic
      recovery in a mouse model of hindlimb ischemia.
AB  - Proteinase-activated receptors (PAR-2) are expressed by the cardiovascular system
      and mediate vasodilation, plasma protein extravasation, and endothelial cell
      proliferation, all regarded as essential steps for neovascularization. We
      investigated the angiogenic action of PAR-2 signaling in vivo. The effect of the
      PAR-2 activating peptide (PAR-2AP, SLIGRL-NH2) was assessed in the absence of
      ischemia, and the therapeutic potential of PAR-2AP and the PAR-2 agonist trypsin
      (at 300 and 1.5 nmol IM daily for 21 days, respectively) was also tested in mice
      subjected to unilateral limb ischemia. PAR-2AP increased capillarity in
      normoperfused adductor skeletal muscles, whereas neither the vehicle of the PAR2
      AP nor the PAR-2 reverse peptide (PAR-2RP, LRGILS-NH2) did produce any effect. In
      addition, both PAR-2AP and trypsin enhanced reparative angiogenic response to
      limb ischemia, an effect that was not produced by PAR-2RP or the vehicle of PAR-2
      agonists. Potentiation of reparative angiogenesis by PAR-2AP or trypsin resulted
      in an accelerated hemodynamic recovery and enhanced limb salvage. In conclusions,
      our study is the first to demonstrate the angiogenic potential of PAR-2
      stimulation in vivo. If similar effects occur in humans, PAR-2AP agonists could
      have some therapeutic potential for the treatment of tissue ischemia.

PMID- 12193469
TI  - Microtubule involvement in the adaptation to altered mechanical load in
      developing chick myocardium.
AB  - Mechanical load regulates ventricular growth, function, and structure from the
      earliest stages of cardiac morphogenesis through senescence. Dramatic changes in
      cardiac form and function have been defined for developing cardiovascular
      systems, and changes in mechanical loading conditions can produce structural
      malformations such as left heart hypoplasia. To date, relatively little is known
      regarding the interactions between changes in mechanical load, morphogenesis, and
      the material properties of the embryonic heart. We tested the hypothesis that
      passive material properties in the embryonic heart change in response to altered
      mechanical load and that microtubules play an important role in this adaptive
      response. We measured biaxial passive stress-strain relations in left ventricular
      (LV) myocardial strips in chick embryos at Hamburger-Hamilton stage 27 following
      left atrial ligation (LAL) at stage 21 to reduce LV volume load and create left
      heart hypoplasia. Following LAL, myocardial stresses at given strains and
      circumferential stiffness increased versus control strips. Western blot analysis
      of LAL embryos showed an increase in both total and polymerized beta-tubulin and
      confocal microscopy confirmed an increase in microtubule density in the LV
      compact layer versus control. Following colchicine treatment, LV stresses and
      stiffness normalized in LAL specimens and microtubule density following
      colchicine was similar in LAL to control. In contrast, Taxol treatment increased
      myocardial stresses and stiffness in control strips to levels beyond LAL
      specimens. Thus, the material properties of the developing myocardium are
      regulated by mechanical load and microtubules play a role in this adaptive
      response during cardiac morphogenesis.

PMID- 12193470
TI  - Phosphoinositide 3-kinase mediates enhanced spontaneous and agonist-induced
      contraction in aorta of deoxycorticosterone acetate-salt hypertensive rats.
AB  - Arteries from deoxycorticosterone acetate (DOCA)-salt and N(omega)-nitro-L
      arginine (L-NNA) hypertensive but not normotensive rats develop spontaneous tone.
      LY294002 and wortmannin, phosphoinositide 3-kinase (PI3-kinase) inhibitors,
      eliminate spontaneous tone. We hypothesized that PI3-kinase protein and/or
      activity was increased in hypertension and contributed to the observed enhanced
      contractility. PI3-kinase activity assays revealed 2-fold higher activity in
      thoracic aorta from DOCA-salt [systolic blood pressure (SBP)=184+/-5 mm Hg]
      compared with sham rats (SBP=111+/-2 mm Hg). Western analyses of aortic
      homogenates revealed the presence of p85alpha, p110alpha, p110beta, and p110delta
      but not p110gamma PI3-kinase subunits; p110delta protein was elevated in aorta of
      hypertensive rats as compared with sham. Aortic homogenates from L-NNA rats also
      had elevated p110beta protein density, but neither L-NNA nor DOCA-salt had
      differences in p85alpha and p110alpha. Total Akt density was unaltered, but pAkt
      was significantly lower in homogenates from DOCA-salt rats. LY294002 (20
      micromol/L) and nifedipine (50 nmol/L) abolished Ca2+-induced spontaneous tone in
      aorta from DOCA-salt rats. However, LY294002 did not alter BayK8644-induced
      contraction, indicating that LY294002 does not inhibit L-type Ca2+ channels
      directly. PTEN (phosphatase and tensin homolog) and pPTEN were expressed but not
      different in aorta from DOCA-salt and sham rats. LY294002 corrected the enhanced
      contraction to KCl and norepinephrine in aorta from DOCA-salt rats. These data
      support an increase in PI3-kinase activity and p110delta density in aorta from L
      NNA and DOCA-salt rats. Importantly, this increase contributes to the enhanced
      contractility observed in two models of hypertension.

PMID- 12193471
TI  - Novel perspectives on the beating rate of the heart.

PMID- 12193472
TI  - Retinoic acid receptor alpha2 is a growth suppressor epigenetically silenced in
      MCF-7 human breast cancer cells.
AB  - Retinoic acid (RA) receptor (RAR) beta2 has been shown to be underexpressed in
      human breast cancer cells, including MCF-7 cells, and recent reports have
      suggested that hypermethylation of the RAR beta2 promoter and 5'-UTR is the
      underlying cause. Here we show that RAR alpha2 is also underexpressed in MCF-7
      breast cancer cells, at both the message and the protein level, relative to
      normal or nontumorigenic breast epithelial cells. Bisulfite sequencing of the CpG
      island in the RAR alpha2 promoter revealed highly penetrant and uniform cytosine
      methylation in MCF-7 cells. Pretreatment with the DNA methyltransferase
      inhibitor, azacytidine, followed by treatment with RA and a histone deacetylase
      inhibitor, trichostatin A, resulted in partial promoter demethylation and RAR
      alpha2 induction, which strongly suggested that promoter hypermethylation is
      responsible for RAR alpha2 underexpression. We compared the outcome of ectopic
      expression in MCF-7 cells of matched levels of RAR alpha2 and RAR beta2. On the
      basis of a clonogenic assay, RAR alpha2 displayed ligand-dependent growth
      suppressive activity similar to that of RARb eta2; thus, 10 and 20 nM RA
      inhibited clonogenic growth by 52 and 80%, respectively, in RAR alpha2
      transfected cells compared with 75 and 77%, respectively, in RAR beta2
      transfected cells. We conclude that the silencing of the RAR alpha2 promoter by
      hypermethylation may play a contributory role in the dysregulation of RA
      signaling in mammary tumorigenesis.

PMID- 12193473
TI  - All-trans-retinoic acid induces nuclear factor kappaB activation and matrix
      metalloproteinase-9 expression and enhances basement membrane invasivity of
      differentiation-resistant human SK-N-BE 9N neuroblastoma Cells.
AB  - A comparison between retinoic acid (RA) differentiation-resistant and
      differentiation-sensitive SK-N-BE neuroblastoma (NB) cell lines revealed an
      association between resistance to differentiation, exhibited by N-myc stable
      transfected SK-N-BE 9N cells, with sensitivity to RA induction of p50/p65 nuclear
      factor kappaB (NF-kappaB) transcription factor activity and induction of matrix
      metalloproteinase (MMP)-9 expression leading to enhanced invasive behavior in
      vitro. These effects were not observed in differentiation-sensitive parental SK-N
      BE or control-transfected SK-N-BE 2N counterparts. RA activated a MMP-9 promoter
      reporter gene construct in SK-N-BE 9N but not parental SK-N-BE or SK-N-BE 2N
      cells through a NF-kappaB element (-600) in association with enhanced p50 mRNA
      expression, reduced cytoplasmic inhibitor of nuclear factor kappaBalpha protein
      levels, and the induction of nuclear p50/p65 containing MMP-9 NF-kappaB site
      binding activity. RA activation of the MMP-9 promoter was inhibited by transient
      overexpression of a dominant-negative inhibitor of nuclear factor kappaBalpha
      protein and stimulated by transient p50 but not p65 overexpression in the absence
      of RA. A limited, nonessential function for activator protein 1 (-74), Ets (
      540), and SP1 (-560) elements within the MMP-9 promoter was revealed by point
      mutation but was not associated with changes in the binding or position of
      complexes constitutive to differentiation-sensitive or -resistant cells. Our data
      indicates that in this model of NB resistance to differentiation that results
      from uncoupled RA regulation of N-myc expression, RA stimulates malignant NB cell
      behavior by inducing nuclear NF-kappaB transcription factor activity, which in
      turn induces MMP-9 expression and stimulation of basement membrane invasive
      capacity involving MMP-9 activity.

PMID- 12193474
TI  - STAT3 activation abrogates growth factor dependence and contributes to head and
      neck squamous cell carcinoma tumor growth in vivo.
AB  - Epidermal growth factor receptor (EGFR) is up-regulated and contributes to the
      loss of growth control in squamous cell carcinoma of the head and neck (SCCHN).
      Previously, we reported an association between autocrine stimulation of EGFR and
      constitutive signal transducers and activators of transcription (STAT) 3
      activation in SCCHN cells in vitro and in vivo. Here, we evaluated the role of
      activated STAT3 in tumor progression and EGFR-independent mitogenic signaling. We
      found that SCCHN cells stably transfected with a dominant active STAT3 construct
      expressed elevated levels of STAT3 target genes, including Bcl-X(L) and cyclin
      D1, and demonstrated increased proliferation in vitro and more rapid tumor growth
      rates in vivo. Cell cycle analysis demonstrated an increased proportion of STAT3
      construct transfectants in G(2)-M. These findings provide evidence that
      constitutive STAT3 activation contributes to tumor growth in SCCHN, independent
      of the EGFR autocrine axis.

PMID- 12193476
TI  - c-Jun NH(2)-terminal kinase pathway in growth-promoting effect of the G protein
      coupled receptor cholecystokinin B receptor: a protein kinase C/Src-dependent
      mechanism.
AB  - The proliferative effects of gastrin on normal and malignant gastrointestinal
      tissues have been shown to be mediated by a G protein-coupled receptor (GPCR),
      the cholecystokinin B receptor. The c-Jun NH(2)-terminal kinase (JNK) pathway has
      been implicated in the regulation of mitogenesis by growth factors or cytokines.
      However, the contribution of this signaling cascade to the proliferative effects
      of GPCR remains largely unknown. Here, we show that cholecystokinin B receptor
      occupancy by gastrin leads to the activation of the JNK pathway. The mechanism
      involves certain protein kinase C isoforms and Src family kinases other than
      p60Src. The complex p130Cas/CrkII, known to be involved in JNK activation, is
      also activated in response to gastrin by a protein kinase C- and Src-dependent
      mechanism. However, gastrin-induced CrkII and JNK pathways are independent. Using
      a dominant negative mutant of c-Jun, we blocked the ability of gastrin to induce
      DNA synthesis, demonstrating a major role of the JNK pathway in the growth
      promoting effect of a GPCR agonist.

PMID- 12193475
TI  - RhoA biological activity is dependent on prenylation but independent of specific
      isoprenoid modification.
AB  - Recent studies showed that specific isoprenoid modification may be critical for
      RhoB subcellular location and function. Therefore, we determined whether the
      function of the highly related RhoA protein is also critically dependent on
      specific isoprenoid modification: (a) in contrast to observations with RhoB or
      Ras proteins, where farnesylated and geranylgeranylated versions showed
      differences in subcellular location, both prenylated versions of RhoA showed the
      same plasma membrane and cytosolic location; (b) a farnesylated version of
      activated RhoA(63L) retained the same diverse functions as the normally
      geranylgeranylated RhoA(63L) protein, and both proteins show indistinguishable
      abilities to stimulate gene expression, cause growth transformation of NIH 3T3
      mouse fibroblasts, to stimulate the motility of T47D human breast epithelial
      cells, and to block HIV-1 viral replication and gene expression; and (c) cells
      expressing farnesylated RhoA retained sensitivity to the growth inhibition caused
      by inhibition of geranylgeranyltransferase I, indicating that other proteins are
      critical targets for inhibitors of geranylgeranylation.

PMID- 12193477
TI  - Vascular endothelial growth factor and Kaposi's sarcoma cells in human skin
      grafts.
AB  - Human cancer cells often produce tumors in animal models that incompletely
      reproduce the histology of the parental tumor. Kaposi's sarcoma (KS) cells, in
      particular, have not produced durable angiogenic lesions in animal models that
      resemble those of KS in humans. We investigated the contribution of transformed
      KS cells, vascular endothelial growth factor (VEGF), and human skin tissue on
      tumor development in a human skin graft/mouse model. High levels of serum VEGF
      (322 pg/ml) were seen in HIV-1-infected persons with KS compared with HIV-1
      infected persons without KS (115 pg/ml). Human KS lesions expressed VEGF in the
      spindle cells. Transformed KS cells expressed the mitogenically active 121-amino
      acid and 165-amino acid isoforms of VEGF. Tumors induced by KS cells implanted in
      the SCID mice grew preferentially in human skin grafts rather than in ungrafted
      murine skin. Tumors induced in the presence of human skin grafts developed
      numerous lumens expressing alpha(v)beta(3) integrin. KS cells inoculated with
      neutralizing anti-VEGF antibody did not form tumors. This study supports an
      important role for VEGF in tumor development and shows how a human tissue can
      preferentially promote tumor growth.

PMID- 12193479
TI  - Anesthesia human resource models: reality or pipe dreams?

PMID- 12193478
TI  - Anesthesiology simulators: networking is the key.

PMID- 12193480
TI  - Best evidence in anesthetic practice: clinical prediction guide: a 14-item index
      predicts 30-day risk of postoperative pneumonia after non-cardiac surgery.

PMID- 12193481
TI  - A worldwide survey of the use of simulation in anesthesia.
AB  - PURPOSE: To gather information regarding the global use of simulation technology
      in education, evaluation and research in anesthesia. METHODS: The WorldWide Web
      was searched and located sites with simulation centres (n = 158) were mailed a 67
      item questionnaire requesting information regarding demographics, personnel,
      education use and research involvement. Comments were solicited. Medical school
      data only are reported in this article. RESULTS: Two web sites were used to
      generate the list of simulation centres. Sixty responses were received (38%),
      with 41 emanating from medical schools. Seventy-seven percent of centres were
      involved in undergraduate education and 85% in postgraduate education. Few
      centres were involved in evaluation and/or competency assessments. Sixty-one
      percent of centres indicated ongoing research with a further 25% interested in
      international collaboration. University or university departmental-based funding
      largely supported simulation technology used in medical schools. The lack of
      financial and human resources was the single most common problem identified by
      respondents. CONCLUSIONS: From the survey responses received, opportunities for
      the simulator to be used for the assessment of performance appear to be under
      utilized. This may be due to the lack of research in this area, lack of
      standardized, valid and reliable tests and the fact that most centres have only
      recently acquired this technology. Further research supporting the use of the
      simulator in education and evaluation is required.

PMID- 12193482
TI  - A physician workforce planning model applied to Canadian anesthesiology:
      assessment of needs.
AB  - PURPOSE: A human resource planning model for anesthesiology is described.
      METHODS: The model uses 'per capita' expenditure for anesthesiologists in Quebec,
      as a measure of clinical services provided to different age/gender groups. The
      future demand for anesthesia services is calculated as the product of 'per
      capita' expenditure and the population projections to a future date. Future
      demand was converted into full-time equivalent (FTE) providers required, by
      dividing by the annual 'units of service' optimally delivered by one FTE
      anesthesiologist. The pattern of age/gender (demographic) consumption of
      anesthesia services in Quebec was compared with data from Ontario to validate its
      use in a planning model. The model was then applied to all provinces and
      territories. RESULTS: The 'per capita' expenditures on anesthesia services in
      Quebec and Ontario showed a regular pattern. Using the model, the estimated 1999
      demand for FTE anesthesiologists to provide clinical services in Quebec is 546
      and 669 for 2016. When non-clinical demands were included, we estimated that
      Quebec's total demand will increase to approximately 730 FTEs in 2016. Similar
      estimates are made for all provinces. The population increase anticipated is
      17.9% but the increase in FTE demand in Canada is 30.9%. CONCLUSION: The model
      showed that the cause of the increased FTE demand for anesthesiologists is a
      combination of increased population and its demographic composition. The relative
      impact of each of these factors varies in different provinces. Effective
      specialty-specific planning models can be designed but they need ongoing
      committed resources and personnel for their usefulness to be maximized.

PMID- 12193483
TI  - A physician workforce planning model applied to Canadian anesthesiology: planning
      the future supply of anesthesiologists.
AB  - PURPOSE: To examine the supply of physician anesthesia providers necessary to
      accommodate the previously described clinical and non-clinical service volume
      needs throughout Canada. METHODS: The Canadian Medical Association (CMA)
      physician database provided baseline specialist anesthesiologists numbers and
      ages as of January 1, 2000. The Royal College of Physician and Surgeons of Canada
      (RCPSC) provided annual anesthesia certificant numbers for the period 1971-2000.
      Combining these data with the separately reported estimates of anesthesia
      provider needs for the years 1999 and 2016, the matching of anesthesia provider
      supply and demand during the period 2000-2016 was examined. RESULTS: The CMA
      database included 2,287 anesthesiologists in Canada on January 1, 2000. The needs
      assessment (clinical and non-clinical) identified the requirement for 2,495 full
      time equivalent (FTE) anesthesiologists in 1999 and 3,265 in 2016 (31% increase).
      Taking into account the ages of current anesthesiologists, the increased future
      requirements and the current rate of graduation from RCPSC-approved training
      programs in Canada a deficit of at least 656 FTEs is identified for the period
      2000-2016 (average 41 per year). CONCLUSIONS: Canada has a current shortage of
      anesthesiologists. Based on the assessment of future needs in Quebec and
      extrapolated to all provinces, this shortage will worsen, unless Canadian
      training programs are expanded or other steps are taken to augment the numbers of
      anesthesia practitioners. Ongoing studies in each province are required to
      validate and update these conclusions.

PMID- 12193484
TI  - Uneventful spinal anesthesia for a patient with carcinoid syndrome managed with
      long-acting octreotide.
AB  - PURPOSE: To present a case of spinal anesthesia in a patient suffering from
      carcinoid syndrome undergoing an inguinal hernia repair. In the past, regional
      anesthesia was considered unacceptable in these patients because of the
      possibility of intraoperative hypotension, hypertension, or bronchospasm.
      Recently, however, the preoperative use of octreotide, the synthetic analogue of
      the naturally occurring hormone somastatin, has been found to prevent these
      complications. Nevertheless, it remains unclear whether the use of this drug in
      patients with carcinoid syndrome allows the possibility of regional anesthesia.
      CLINICAL FINDINGS: We report the uneventful use of spinal anesthesia in a patient
      suffering from carcinoid syndrome treated with long-acting octreotide. With
      careful attention to volume status of the patient and low volume of local
      anesthetics (10 mg hyperbaric bupivacaine 0.5%) supplemented with intrathecal
      narcotics (fentanyl 20 micro g), we were able to prevent any episodes of
      intraoperative hypotension in this patient. Octreotide was available in the
      operating theatre in case of an emergency. One of the original aspects of this
      case report is that the patient received long-acting octreotide (once a month
      administration) instead of the usual daily dose. In addition this is one of the
      few reports of spinal anesthesia administered to a patient with carcinoid
      syndrome. CONCLUSION: Preoperative octreotide may result in more favourable
      conditions for regional anesthesia in patients with carcinoid syndrome. However,
      further studies will be required to confirm the favourable outcome observed in
      this patient.

PMID- 12193485
TI  - Variable hemodynamic fluctuations during resection of multicentric extraadrenal
      pheochromocytomas.
AB  - PURPOSE: To report the perioperative management and the serious hemodynamic
      fluctuations during manipulation of an organ of Zuckerkandl tumour in a patient
      undergoing resection of multicentric extraadrenal pheochromocytomas. CLINICAL
      FINDINGS: A 28-yr-old man who had undergone at age 12 a laparotomy for excision
      of an extraadrenal pheochromocytoma complained of paroxysmal headache, occasional
      sweating and palpitations. The arterial blood pressure (BP) was 200/100 mmHg. A
      24-hr-urine collection showed catecholamines 5076 microg x 24 hr(-1) (normal < 25
      microg x 24 hr(-1)). Computed tomography of the abdomen revealed two
      retroperitoneal masses, one adjacent to the lower pole of the right kidney and a
      second larger mass located at the aortic bifurcation in the region of the organ
      of Zuckerkandl. The patient was scheduled for excision of multiple extraadrenal
      pheochromocytomas. He was prepared preoperatively for two weeks with prazosin 1
      mg po q six hours and propranolol 10 mg tid. Manipulation of the infrarenal
      tumour was uneventful but manipulation of the Zuckerkandl tumour resulted in
      severe hypertensive episodes with BP ranging from 200/100 to 320/120 mmHg.
      Surgery was interrupted temporarily; the hypertensive crisis was controlled by
      the infusion of sodium nitroprusside and by iv phentolamine and esmolol.
      CONCLUSION: In a patient undergoing resection of recurrent multicentric
      extraadrenal pheochromoctyomas, severe hypertensive episodes occurred during
      manipulation of one tumour but not during manipulation of the other. This may be
      attributed to inadequate preparation of the patient, difficult surgical
      dissection of the large Zuckerkandl pheochromocytoma, and/or secondary to an
      excessive and different pattern of release of catecholamines during manipulation
      of the Zuckerkandl tumour.

PMID- 12193486
TI  - A modification of the inter-cuff technique of IVRA for use in knee arthroscopy.
AB  - PURPOSE: To describe a modified approach to intravenous regional anesthesia
      (IVRA) for operations on the knee joint. CLINICAL FEATURES: A 52-yr-old male
      presenting for knee arthroscopy was anesthetized by IVRA using only 40 mL of
      lidocaine 0.5%. After performing IVRA in the routine way an additional below knee
      tourniquet was used and inflated after local anesthetic exsanguination towards
      the knee. Operation was performed without the need for further analgesic.
      CONCLUSION: The technique allowed the use of a small anesthetic volume for IVRA
      on the lower limb, thus decreasing the potential risk of local anesthetic
      toxicity.

PMID- 12193487
TI  - Sciatic nerve block with bupivacaine-loaded microspheres prevents hyperalgesia in
      an inflammatory animal model.
AB  - PURPOSE: The aim of this study was to evaluate the effect of different durations
      of local anesthetic neural blockade on hyperalgesia after carrageenan
      infiltration in a rat model. METHODS: Inflammation was obtained by injection of
      carrageenan in the righ hind paw. Hyperalgesia was determined by measuring the
      threshold of response to increasing mechanical stimuli on the contralateral and
      on the ipsilateral paw. The development of edema was measured. After
      identification of the sciatic nerve by nerve stimulation, blockade was performed
      either one hour before or after carrageenan infiltration. Animals were randomly
      assigned into three groups: without sciatic nerve block (control group; n = 20),
      block with bupivacaine (B) and block with bupivacaine-loaded microspheres (B-Ms)
      injection before or after carrageenan infiltration (n = 10 for each group).
      RESULTS: Carrageenan infiltration in the control group induced a severe
      ipsilateral and contralateral hyperalgesia. After blockade with B (duration = 2
      +/- 0.5 hr) hyperalgesia was present and delayed only by the duration of the
      local anesthetic effect. A longer duration of block achieved with B-Ms (duration
      greater than five hours), was associated with the absence of development of both
      ipsilateral and contralateral hyperalgesia. No preemptive effect was recorded.
      CONCLUSION: B-Ms as a drug delivery system prolongs the duration of neural
      blockade and avoids hyperalgesia phenomena in this rat model of inflammation.

PMID- 12193488
TI  - Iliohypogastric-ilioinguinal peripheral nerve block for post-Cesarean delivery
      analgesia decreases morphine use but not opioid-related side effects.
AB  - PURPOSE: To examine if ilioinguinal-iliohypogastric nerve block could reduce the
      need for post-Cesarean delivery morphine analgesia and thus reduce the incidence
      of opioid related adverse-effects. METHODS: A multi-level technique for
      performing the nerve block with bupivacaine was developed and then utilized in
      this two-part study. Part one was a retrospective assessment of Cesarean delivery
      patients with and without ilioinguinal-iliohypogastric blocks to determine if the
      technique reduced patient controlled analgesia morphine use and thus would
      warrant further study. The second phase was a randomized double-blind placebo
      controlled trial to compare post-Cesarean morphine use and the appearance of
      opioid-related side effects between the anesthetic and placebo-injected groups.
      RESULTS: Both phases demonstrated that our method of ilioinguinal-iliohypogastric
      nerve block significantly reduced the amount of iv morphine used by patients
      during the 24 hr following Cesarean delivery. In the retrospective assessment,
      morphine use was 49 +/- 30 mg in the block group vs 79 +/- 25 mg in the no block
      group (P = 0.0063). For the prospective trial, patients who received nerve blocks
      with bupivacaine had a similar result, self-administering 48 +/- 27 mg of
      morphine over 24 hr compared to 67 +/- 28 mg administered by patients who
      received infiltrations of saline. However, despite the significant decrease in
      morphine use, there was no reduction in opioid-related adverse effects: the
      incidences of nausea were 41% and 46% (P = 0.70) and for itching were 79% and 63%
      (P = 0.25) in the placebo and nerve block groups, respectively. CONCLUSION: A
      multi-level ilioinguinal-iliohypogastric nerve block technique can reduce the
      amount of systemic morphine required to control post-Cesarean delivery pain but
      this reduction was not associated with a reduction of opioid related adverse
      effects in our study group.

PMID- 12193489
TI  - Plasma lidocaine concentrations are higher in twin compared to singleton newborns
      following epidural anesthesia for Cesarean delivery.
AB  - PURPOSE: This study compares plasma lidocaine concentrations in 16-sets of twin
      neonates to 16-singleton neonates all of whom were delivered by Cesarean section
      under lumbar epidural anesthesia (LEA). METHODS: Lidocaine 1.5% with epinephrine
      5 microg x mL(-1) was used for activation of LEA. Upon delivery plasma lidocaine
      concentrations were measured from the maternal vein (MV), neonatal umbilical vein
      (UV) and umbilical artery (UA) using TDx fluorescence polarization immunoassay.
      RESULTS: MV lidocaine concentrations were similar in both twin and singleton
      mothers. Both mean lidocaine UV and UA levels were 35% higher in twin A (first
      delivered) compared to the singleton neonate, (P < 0.01, t test). Similarly, twin
      B mean UV and UA lidocaine levels were 35% and 53% higher than the singleton
      value (P < 0.01). Mean UV and UA lidocaine fetal/maternal ratios in both twins
      were at least 18% higher than the singleton value (P < 0.05). CONCLUSION: Even
      though there were no differences in neonatal outcome, a potential does exist for
      high plasma lidocaine concentrations in twin fetuses, suggesting that the total
      maternal dose of lidocaine must be regulated carefully.

PMID- 12193490
TI  - Epinephrine does not reduce the plasma concentration of lidocaine during
      continuous epidural infusion in children.
AB  - PURPOSE: During continuous epidural anesthesia with lidocaine, plasma
      monoethylglycinexylidide (MEGX), an active metabolite of lidocaine, increases
      continuously. We assessed the effect of epinephrine on the absorption of
      lidocaine and the accumulation of MEGX during continuous epidural anesthesia in
      children. METHODS: Anesthesia was administered as an initial bolus of 5 mg x kg(
      1) of 1% lidocaine solution followed by continuous infusion at 2.5 mg x kg(-1) x
      hr(-1). Patients in the control group (n = 8) received lidocaine alone, while
      patients in the epinephrine group (n = 8) received lidocaine + epinephrine (5
      microg x mL(-1)). Concentrations of lidocaine and its active metabolite, MEGX,
      were measured in plasma samples obtained after 15 min, 30 min, and one, two,
      three, four, and five hours of infusion using high-performance liquid
      chromatography with ultraviolet detection. RESULTS: Plasma lidocaine
      concentrations were higher in samples from the control group for the first hour;
      however, after two hours the levels were the same in all samples. Plasma MEGX
      levels increased continuously in both groups and were significantly higher in the
      control group samples. The sum of lidocaine + MEGX was higher in the control
      group for the first two hours but there was no significant difference between
      groups after three hours. CONCLUSIONS: Reduction of the potential for systemic
      toxicity by the addition of epinephrine to lidocaine is limited, because the
      reduction of the sum of the plasma concentrations of lidocaine and its active
      metabolite MEGX is small and limited to the initial phase of infusion.

PMID- 12193491
TI  - Intrathecal sufentanil-morphine shortens the duration of intubation and improves
      analgesia in fast-track cardiac surgery.
AB  - PURPOSE: To compare the effect of combined intrathecal morphine and sufentanil
      with low-dose iv sufentanil during propofol anesthesia for fast-track cardiac
      surgery. METHODS: Twenty-four consecutive patients with normal cardiopulmonary
      function who were scheduled for elective cardiac surgery were randomized to
      receive either a continuous iv infusion of sufentanil 0.9 to 1.8 microg x kg(-1)
      x min(-1) (13 patients), or a single lumbar intrathecal dose of sufentanil 50
      micro g and morphine 500 micro g (11 patients). We prospectively studied
      perioperative analgesia, time to extubation and early postoperative maximal
      inspiratory capacity in the two groups. In the intensive care unit, the medical
      and nursing staff were blinded to the analgesic technique. RESULTS: Intrathecal
      sufentanil morphine allowed a shorter duration of intubation (104 +/- 56.5 min vs
      213 +/- 104 min; P = 0.01), reduced the need for postoperative analgesia with
      nicomorphine (equipotent to morphine) (0.7 +/- 0.4 mg x hr(-1) vs 1.2 +/- 0.4 mg
      x hr(-1); P = 0.008) and improved postoperative maximal inspiratory capacity
      (53.4 +/- 16.1 vs 38.4 +/- 12.5% of the norm; P = 0.05). CONCLUSION: In low-risk
      patients undergoing coronary artery bypass graft or valve surgery, combined
      intrathecal sufentanil and morphine with a target-controlled infusion of propofol
      satisfies the goals of fast-track cardiac surgery.

PMID- 12193492
TI  - Alfentanil does not increase resistance of the respiratory system in ASA I
      patients ventilated mechanically during general anesthesia.
AB  - PURPOSE: Several experimental and clinical studies have demonstrated a direct
      bronchoconstrictor effect of opioids on smooth bronchial musculature following iv
      administration. The aim of this study was to evaluate the effects of alfentanil
      on respiratory system mechanics in a group of ASA I patients ventilated
      mechanically during general anesthesia. CLINICAL FEATURES: Twenty consecutive ASA
      I patients (ten men and ten women) scheduled for general surgery interventions
      were studied (mean age 45.4 +/- 9.9 yr, mean weight 61.9 +/- 6.7 kg). Exclusion
      criteria were a history of chronic obstructive pulmonary disease, asthma or other
      pulmonary disease, atopy, wheezes, smoking and age below 18 yr. Subjects were
      randomly divided in two groups: Group A, receiving alfentanil at a 15 microg x
      kg(-1) dose and Group B receiving alfentanil at a 30 microg x kg(-1) dose.
      Respiratory mechanic variables were acquired at baseline (T0) and after three,
      ten and 15 min (T1, T2 and T3, respectively). We compared the basal values to the
      values measured at each time interval; basal values, prior to drug
      administration, served as control for each patient. P values < 0.05 were
      considered statistically significant. RESULTS: We did not observe significant
      differences in respiratory mechanic variables after the administration of
      alfentanil, 15 and 30 microg x kg(-1). More specifically, respiratory system
      compliance and the different subcomponents of respiratory system resistances
      (i.e., maximum, minimum and delta resistance of respiratory system) were within
      normal limits and did not vary after alfentanil administration. CONCLUSION: No
      respiratory adverse effect was reported after alfentanil iv administration.

PMID- 12193493
TI  - Hypercapnic respiratory failure and partial upper airway obstruction during high
      frequency oscillatory ventilation in an adult burn patient.
AB  - PURPOSE: To present a case of severe hypercapnic respiratory failure in an adult
      burn patient and to describe our clinical problem solving approach during support
      with an unconventional mode of mechanical ventilation. CLINICAL FEATURES: A 19-yr
      old male with smoke inhalation and flame burns to 50% total body surface area was
      admitted to the Ross Tilley Burn Centre. High frequency oscillatory ventilation
      (HFOV) was initiated on day three for treatment of severe hypoxemia. By day four,
      the patient met consensus criteria for acute respiratory distress syndrome. On
      day nine, alveolar ventilation was severely compromised and was characterized by
      hypercapnea (PaCO(2) 136 mmHg) and acidosis (pH 7.10). Attempts to improve CO(2)
      elimination by a decrease in the HFOV oscillatory frequency and an increase in
      the amplitude pressure failed. An intentional orotracheal tube cuff leak was also
      ineffective. A 6.0-mm nasotracheal tube was inserted into the supraglottic
      hypopharynx to palliate presumed expiratory upper airway obstruction. After
      nasotracheal tube placement, an intentional cuff leak of the orotracheal tube
      improved ventilation (PaCO(2) 81 mmHg) and relieved the acidosis (pH 7.30). The
      improvement in ventilation (with normal oxygen saturation) was sustained until
      the patient's death from multiple organ dysfunction four days later. CONCLUSION:
      During HFOV in burn patients, postresuscitation edema of the supraglottic upper
      airway may cause expiratory upper airway obstruction. The insertion of a
      nasotracheal tube, combined with an intentional orotracheal cuff leak may improve
      alveolar ventilation during HFOV in such patients.

PMID- 12193494
TI  - Cricoarytenoid arthritis: a cause of acute upper airway obstruction in rheumatoid
      arthritis.
AB  - PURPOSE: To report acute upper airway obstruction due to cricoarytenoid
      arthritis, a well known but uncommon complication of rheumatoid arthritis.
      CLINICAL FEATURES: We report the case of a 70-yr-old female scheduled for a
      colostomy who had been suffering from rheumatoid arthritis for 17 years.
      Preoperative history and physical examination revealed no cardiopulmonary
      compromise. Anesthesia was induced while an assistant immobilized the cervical
      spine and an atraumatic intubation was performed. Surgery was uneventful. Muscle
      paralysis was reversed, demonstrated by normalization of the train-of-four
      response, and the patient was extubated awake. Shortly postextubation, the
      patient developed inspiratory stridor, which disappeared after a second dose of
      neostigmine. The patient was transported to the postanesthesia care unit. Just
      prior to arrival the patient once again developed inspiratory stridor, became
      distressed, and oxygen saturation decreased. Direct laryngoscopy followed by a
      nasal fibreoptic examination of the larynx was performed. Cricoarytenoid
      arthritis secondary to rheumatoid arthritis with airway compromise was diagnosed.
      An uneventful awake tracheostomy was performed. The patient was discharged on day
      ten with a colostomy and a tracheostomy in place. One month postdischarge the
      patient's trachea was decannulated. On follow-up, a normal voice and mobile cords
      were observed. CONCLUSION: Cricoarytenoid arthritis is an infrequent complication
      of rheumatoid arthritis. A thorough history and physical examination are
      necessary to recognize signs and symptoms of cricoarytenoid arthritis. Prompt
      recognition of airway obstruction due to cricoarytenoid arthritis is essential
      for appropriate management.

PMID- 12193495
TI  - Airway management after upper cervical spine injury: what have we learned?
AB  - PURPOSE: Survival after atlanto-axial-occipital ligamentous injury is uncommon
      and experience with the immediate clinical management of these patients is
      similarly low. There has been considerable work published recently with respect
      to airway management in similar patients and a review of this material was
      undertaken. METHODS: Medline searches were performed to seek out the English
      language literature using the key words and phrases: cervical spinal injury;
      atlanto-occipital dislocation; atlanto-occipital disarticulation; and airway
      management after spinal injury. The titles were culled for materials relevant
      particularly to upper cervical spinal injury, these were obtained and reviewed.
      The bibliographies of these articles were searched to ensure that the review
      would be complete. RELEVANT FINDINGS: The majority of cervical spinal movement
      occurring during direct laryngoscopy is concentrated in the upper cervical spine.
      The magnitude of movement during airway management rarely exceeds the
      physiological limits of the spine. Movement is reduced by in-line immobilization
      but traction forces cause clinically important distraction and should be avoided.
      Indirect techniques for tracheal intubation cause less cervical movement than
      does the direct laryngoscope. Survival after severe upper ligamentous injury is
      uncommon but intact survival occurs. Missed diagnosis is common and associated
      with a high incidence of severe secondary injury. Failure to immobilize the spine
      is deemed to be the most relevant factor in secondary injury. CONCLUSIONS:
      Patients who survive severe upper cervical ligamentous injury and present to
      hospital are uncommon. However, of those who do, both intact survival and
      survival with limited neurological sequelae do occur. Meticulous airway care with
      maintenance of alignment and provision of continuous cervical immobilization are
      an integral component of care in these patients.

PMID- 12193496
TI  - Five percent, 7.5% or 10% hypertonic saline prevents delayed neuronal death in
      gerbils.
AB  - PURPOSE: To clarify the appropriate concentration and dose of hypertonic saline
      solution (HSS) for preventing delayed neuronal death in the hippocampal CA1
      subfield after transient forebrain ischemia in gerbils. METHODS: Thirty gerbils
      were randomly assigned to five groups: physiological saline solution (PSS) group,
      ischemia/reperfusion treated with PSS 2 mL x kg(-1); 5% HSS group, treated with
      5% HSS 2 mL x kg(-1); 7.5% HSS group, treated with 7.5% HSS 2 mL x kg(-1); 10%
      HSS group, treated with 10% HSS 2 mL x kg(-1); 20% HSS group, treated with 20%
      HSS 2 mL x kg(-1). Transient forebrain ischemia was induced by occluding the
      bilateral common carotid arteries for four minutes. Five days later,
      histopathological changes in the hippocampal area were examined, and the
      degenerative ratio of the pyramidal cells were measured according to the
      following formula: (number of degenerative pyramidal cells/total number of
      pyramidal cells per 1 mm of hippocampal CA1 subfield) x 100. RESULTS: In PSS and
      20% groups, neuronal cell damage was observed five days after ischemia. In the
      other three groups, these changes were not observed. The degenerative ratios of
      pyramidal cells were as follows; PSS group: 91.6 +/- 5.6%, 5% HSS group: 7.2 +/-
      1.6%, 7.5% group: 8.3 +/- 1.4%, 10% HSS group: 6.2 +/- 1.1%, 20% HSS group: 85.8
      +/- 8.7% (P < 0.05; PSS and 20% HSS vs three other groups). CONCLUSION: This
      study demonstrates that 5, 7.5 or 10% HSS 2 mL x kg(-1) may prevent delayed
      neuronal death in the hippocampal CA1 subfield after cerebral
      ischemia/reperfusion in gerbils.

PMID- 12193498
TI  - Burst suppression ratio is the only determinant for BIS values below 30.

PMID- 12193499
TI  - Increasing tidal volumes and PEEP is an effective method of alveolar recruitment.

PMID- 12193500
TI  - Injury to the liver and spleen after diagnostic ERCP.

PMID- 12193501
TI  - Use of a remifentanil PCA for a patient with multiple rib fractures.

PMID- 12193502
TI  - Unexpected beneficial effect of stellate ganglion block in a schizophrenic
      patient.

PMID- 12193503
TI  - More on lingual tonsillar hypertrophy.

PMID- 12193504
TI  - Fast-tracking in ambulatory anesthesia: a new concept? Not!

PMID- 12193505
TI  - Epidural analgesia and maternal fever.

PMID- 12193506
TI  - Bedside indices to predict weaning from mechanical ventilation.

PMID- 12193507
TI  - Guilt by association?

PMID- 12193508
TI  - Is there a "right not to be born"? Reproductive decision making, options and the
      right to information.

PMID- 12193509
TI  - Cytomegalovirus transmission from breast milk in premature babies: does it
      matter?
AB  - There is evidence that CMV is commonly present in breast milk and is often
      transmitted to babies. CMV infection acquired postnatally can cause serious
      disease in very premature babies. Interventions to remove CMV from breast milk
      are possible but may damage other important constituents.

PMID- 12193511
TI  - Routine pulse oximetry in the asymptomatic newborn.
AB  - OBJECTIVE: To assess the effect of routine measurement of postductal oxygen
      saturation as an adjunct to routine clinical examination in the asymptomatic
      newborn. DESIGN AND SETTING: Prospective study in a district general hospital.
      PATIENTS: All 6166 infants inborn between 1 April 1999 and 31 March 2001.
      INTERVENTION: Oxygen saturation was measured over two minutes, after the age of 2
      hours and before discharge, in one foot of all babies not admitted directly to
      the neonatal unit. Babies with fractional (as opposed to functional) oxygen
      saturation (SaO(2)) below 95% were examined by the midwife. If this examination
      was abnormal or if normal but further measurements were below 95%, an
      echocardiogram was performed. All babies with cardiac malformations diagnosed by
      1 year of age were identified from databases maintained at the regional
      cardiology referral unit and the regional congenital malformation survey.
      RESULTS: Measurements were made in 98% of eligible babies. A fractional SaO(2)
      less than 95% was found in 5% but persisted in only 1%. Structural cardiac
      malformations were found in 50 (8.1/1000), 26 of whom had isolated ventricular
      septal defects. Of the remaining 24 with other cardiac malformations, attention
      was first drawn to six by low SaO(2), and four more, first noticed for other
      reasons, also had low SaO(2). Low SaO(2) also first drew attention to 13 other
      babies ill for other reasons. CONCLUSION: Newborn babies with important cardiac
      malformations are often asymptomatic initially and the yield from clinical
      examination is poor. Measuring postductal saturation routinely in newborn babies
      before discharge is easy and can alert staff to ill babies.

PMID- 12193510
TI  - Retinopathy of prematurity: recent advances in our understanding.
AB  - Retinopathy of prematurity (ROP) has been recognised as an important cause of
      childhood visual impairment and blindness since the 1940s when improved
      facilities and treatment increased the survival rate of premature infants.
      Although its incidence and severity have been decreasing in developed countries
      over the past two decades, both are increasing in developing nations. ROP is
      consequently targeted as an important but avoidable disease. This review provides
      an updated summary and discussion of much of the work that has been produced
      through population, animal, cell culture, and genetic research. The authors
      examine the prevalence, risk factors, and possible causes of the disease with a
      particular focus on genetic studies. They conclude that while significant
      reductions in the disease have occurred in developed countries, further research
      is required to fully understand and prevent the disease. In the meantime,
      development and implementation of appropriate screening and treatment strategies
      will be critical in reducing blindness in developing countries.

PMID- 12193512
TI  - Measurement of right ventricular volume in healthy term and preterm neonates.
AB  - BACKGROUND: Pulmonary hypertension is associated with worse perinatal outcomes in
      infants with respiratory disorders. In such infants right ventricular dysfunction
      may result in poor pulmonary blood flow. OBJECTIVE: To evaluate the
      practicability and repeatability of echocardiographic measurements of right
      ventricular volume in healthy term and preterm neonates, and to follow changes in
      right ventricular volume over the first 2 days of life. METHODS: Serial
      echocardiographic examinations were performed on day 0, 1, and 2 on healthy term
      and preterm neonates. Two methods of estimating right ventricular volume were
      assessed: the ellipsoid approximation and Simpson's stacked discs methods.
      Systolic and diastolic volumes on days 1 and 2 were compared with baseline values
      on day 0. Term and preterm volumes were compared at the same time points.
      RESULTS: Thirty five infants were recruited, 18 term and 17 preterm. Right
      ventricular volumes were significantly lower on day 1 and day 2 than baseline in
      both term and preterm infants. Median (interquartile range) end systolic and
      diastolic volumes for term infants on days 0, 1, and 2 were 1.04 (0.88-1.44),
      0.82 (0.70-1.03), 0.92 (0.72-0.97) ml/kg and 2.21 (2.10-2.75), 2.05 (1.81-2.38),
      1.91 (1.81-2.13) ml/kg respectively. In preterm infants the values were 1.09
      (0.91-1.16), 0.72 (0.54-0.91), 0.61 (0.54-0.76) ml/kg and 2.09 (1.71-2.25), 1.47
      (1.23-1.98), 1.43 (1.22-1.78) ml/kg respectively. CONCLUSION: Right ventricular
      volume decreases over the first 2 days of life in healthy term and preterm
      infants.

PMID- 12193514
TI  - Patterns of antropyloric motility in fed healthy preterm infants.
AB  - BACKGROUND: Antropyloric motility is important for regulation of gastric emptying
      and has not been adequately characterised in premature infants. AIM: To evaluate
      fed patterns of antropyloric motility in premature infants. SUBJECTS: Forty three
      healthy premature infants, 30-38 weeks of postmenstrual age. METHODS:
      Postprandial antropyloric motility was measured using a micromanometric feeding
      assembly (outer diameter 1.8 mm) incorporating a pyloric sleeve sensor. The
      occurrence of isolated pyloric pressure waves (IPPWs) and antral pressure wave
      sequences (PWSs) was characterised. Sequences were further classified as being
      antegrade, synchronous, antegrade-synchronous, and retrograde according to the
      direction of propagation. RESULTS: A total of 7289 pressure wave events were
      recorded, 48% IPPWs and 52% PWSs (18% antegrade, 12% synchronous, 13% antegrade
      synchronous, 2% retrograde, and 7% undefined). IPPWs predominated in the first
      postprandial hour, peaking at 30-60 minutes. PWSs predominated in the period
      after one hour postprandially. Mean (SEM) half gastric emptying time was 42 (4)
      minutes. CONCLUSIONS: Monitoring of antropyloric motor patterns in healthy
      premature infants indicates that the neuroregulatory mechanisms responsible for
      the coordination of antropyloric motility and gastric emptying are well developed
      by 30 weeks of postmenstrual age.

PMID- 12193515
TI  - Effects of maternal tobacco smoking, sleeping position, and sleep state on
      arousal in healthy term infants.
AB  - OBJECTIVES: To investigate whether a history of maternal tobacco smoking affected
      the maturation of arousal responses and whether sleeping position and infant age
      alters these relations. DESIGN: Healthy term infants (13 born to mothers who did
      not smoke and 11 to mothers who smoked during pregnancy) were studied using
      daytime polysomnography on three occasions: (a) two to three weeks after birth,
      (b) two to three months after birth, and (c) five to six months after birth.
      Multiple measurements of arousal threshold in response to air jet stimulation
      were made in both active sleep (AS) and quiet sleep (QS) when infants slept both
      prone and supine. RESULTS: Maternal smoking significantly elevated arousal
      threshold in QS when infants slept supine at 2-3 months of age (p<0.05). Infants
      of smoking mothers also had fewer spontaneous arousals from QS at 2-3 months in
      both prone (p<0.05) and supine (p<0.001) sleeping positions. In infants of non
      smoking mothers, arousal thresholds were elevated in the prone position in AS at
      2-3 months (p<0.01) and QS at 2-3 weeks (p<0.05) and 2-3 months (p<0.001).
      CONCLUSIONS: Maternal tobacco smoking significantly impairs both stimulus induced
      and spontaneous arousal from QS when infants sleep in the supine position, at the
      age when the incidence of sudden infant death syndrome is highest.

PMID- 12193517
TI  - Characterising doctor-parent communication in counselling for impending preterm
      delivery.
AB  - OBJECTIVE: To examine the counselling of women admitted to hospital in preterm
      labour. Such women and their partners are often asked to participate in difficult
      decisions including mode of delivery, fetal monitoring, and resuscitation. STUDY
      DESIGN: Questionnaire based descriptive study. STUDY SETTING: A tertiary level
      perinatal referral centre. PATIENTS: Forty-nine women in preterm labour at 22-30
      weeks gestation, admitted in two separate periods between March 1997 and May
      1999. INTERVENTION AND OUTCOME MEASURE: Within 24 hours of counselling, parents
      were asked to complete a questionnaire assessing recall of the management plan,
      desire for involvement in decision making, anxiety, and feelings of control over
      their health. A parallel questionnaire was completed by the clinicians. RESULTS:
      Parents and clinicians on recall agreed well about obstetric issues but poorly
      about neonatal issues. Overall 27% of parents felt: "I would prefer to have the
      doctors advise me, rather than asking me to decide". In 79% of cases, clinicians
      believed parents preferred advice rather than to make decisions, but in 45% of
      these, they misidentified those who wished to make their decisions. Anxiety
      levels for one third of the mothers were high, and associated with poorer
      concordance of recall between parents and clinicians. CONCLUSIONS: Serious
      deficiencies exist in parent-clinician encounters during extremely preterm
      labour. Concordance between parents and clinicians is poor and anxiety very high.
      A quarter of parents appear to prefer to relinquish decision making autonomy, but
      clinicians cannot correctly identify this subgroup. Standardised counselling in
      the perinatal period, using formal decision aids, should be investigated.

PMID- 12193516
TI  - Central and autonomic system signs with in utero drug exposure.
AB  - AIMS: To determine risk for central nervous system/autonomic nervous system
      (CNS/ANS) signs following in utero cocaine and opiate exposure. METHODS: A
      multisite study was designed to determine outcomes of in utero cocaine and opiate
      exposure. A total of 11 811 maternal/infant dyads were enrolled. Drug exposed
      (EXP) infants were identified by maternal self report of cocaine or opiate use or
      by meconium testing. Of 1185 EXP, meconium analysis confirmed exposure in 717 to
      cocaine (CO) only, 100 to opiates (OP), and 92 to opiates plus cocaine (OP+CO);
      276 had insufficient or no meconium to confirm maternal self report. Negative
      exposure history was confirmed in 7442 by meconium analysis and unconfirmed in
      3184. Examiners masked to exposure status, assessed each enrolled infant. Using
      generalised estimating equations, adjusted odds ratios (OR) and 95% confidence
      intervals (CI) were estimated for manifesting a constellation of CNS/ANS outcomes
      and for each sign associated with cocaine and opiate exposure. RESULTS:
      Prevalence of CNS/ANS signs was low in CO, and highest in OP+CO. Signs were
      significantly related to one another. After controlling for confounders, CO was
      associated with increased risk of manifesting a constellation of CNS/ANS
      outcomes, OR (95% CI): 1.7 (1.2 to 2.2), independent of OP effect, OR (95% CI):
      2.8 (2.1 to 3.7). OP+CO had additive effects, OR (95% CI): 4.8 (2.9 to 7.9).
      Smoking also increased the risk for the constellation of CNS/ANS signs, OR (95%
      CI) of 1.3 (1.04 to 1.55) and 1.4 (1.2 to 1.6), respectively, for use of less
      than half a pack per day and half a pack per day or more. CONCLUSION: Cocaine or
      opiate exposure increases the risk for manifesting a constellation of CNS/ANS
      outcomes.

PMID- 12193518
TI  - Comparative epidemiology of sudden infant death syndrome and sudden intrauterine
      unexplained death.
AB  - BACKGROUND: Unexplained antepartum stillbirth and sudden infant death syndrome
      (SIDS) are major contributors to perinatal and infant mortality in the western
      world. A relation between them has been suggested. As an equivalent of SIDS, only
      cases validated by post mortem examination are diagnosed as sudden intrauterine
      unexplained death (SIUD). OBJECTIVE: To test the hypothesis that SIDS and SIUD
      have common risk factors. METHODS: Registration comprised all stillbirths in Oslo
      and all infant deaths in Oslo and the neighbouring county, Akershus, Norway
      during 1986-1995. Seventy six cases of SIUD and 78 of SIDS were found, along with
      582 random controls surviving infancy, all singletons. Odds ratios were obtained
      by multiple logistic regression analysis. RESULTS: Whereas SIUD was associated
      with high maternal age, overweight/obesity, smoking, and low education, SIDS was
      associated with low maternal age, smoking, male sex, multiparity, proteinuria
      during pregnancy, and fundal height exceeding +2 SD. Thus the effects of maternal
      age were opposite in SIUD and SIDS (adjusted odds ratio 1.39 (95% confidence
      interval 1.17 to 1.66) per year, p < 0.0005). Heavy smoking, male sex, and a
      multiparous mother was less likely in SIUD than in SIDS (0.22 (0.06 to 0.83),
      0.22 (0.07 to 0.78), and 0.03 (<0.01 to 0.17) respectively). Overweight/obesity
      and low fundal height were more common in SIUD than in SIDS (7.45 (1.49 to 37.3)
      and 13.8 (1.56 to 122) respectively). CONCLUSIONS: The differences in risk
      factors do not support the hypothesis that SIDS and SIUD have similar
      determinants in maternal or fetal characteristics detectable by basic antenatal
      care.

PMID- 12193519
TI  - Cerebral palsy in twins: a national study.
AB  - BACKGROUND: Cerebral palsy is more common in twins than singletons. Among twins,
      if one twin suffers a fetal death or dies in infancy, the prevalence of cerebral
      palsy in the surviving co-twin is considerably increased, and those from like-sex
      pairs are particularly at high risk. AIM: To compare birthweight specific
      cerebral palsy prevalence in like-sex and unlike-sex twins where both twins
      survive infancy and to provide a comparative and composite picture of cerebral
      palsy prevalence according to whether a co-twin died or where both twins
      survived. METHODS: Parents of twins born in England and Wales in 1994 and 1995
      completed a booklet with open ended questions asking whether their twins had any
      medical, physical, visual, genetic, or chromosomal problems. Any mention of
      cerebral palsy, hemiplegia, diplegia, or quadriplegia allowed the child to be
      included as a case of cerebral palsy. Birthweight specific prevalence rates of
      cerebral palsy were determined for like and unlike-sex twins in birthweight
      groups < 1000 g, 1000-1499 g, 1500-1999 g, 2000-2499 g, and > or = 2500 g.
      RESULTS: When both twins survived infancy, like-sex were at greater risk of
      cerebral palsy than unlike-sex twins, but the difference was not statistically
      significant. If both twins survived infancy, the birthweight specific prevalence
      of cerebral palsy was significantly less than if the co-twin had died.
      CONCLUSIONS: Among the generality of twins, like-sex compared with unlike-sex
      twins are at greater risk of cerebral palsy particularly if one twin suffers a
      fetal or infant death. Although it is not possible to subdivide the twins
      according to zygosity, it is postulated that monozygosity and, specifically,
      monochorionicity may be the crucial feature that leads to the higher prevalence
      of cerebral impairment among like-sex twins.

PMID- 12193520
TI  - Portal vein thrombosis causing neonatal cerebral infarction.
AB  - Neonatal cerebral infarction often occurs in the absence of known risk factors.
      Two such cases are described in which portal vein thrombosis was documented
      during two dimensional echocardiography. In both cases, infarcts were consistent
      with embolic events. A novel mechanism is proposed, which may explain some cases
      of "idiopathic" neonatal cerebral infarction.

PMID- 12193521
TI  - Population based, controlled study of behavioural problems and psychiatric
      disorders in low birthweight children at 11 years of age.
AB  - OBJECTIVE: To evaluate the risk of long term behavioural problems and psychiatric
      disorders associated with being born with low birth weight. DESIGN/STUDY GROUPS:
      A population based, controlled follow up study at 11 years of age of 130 low
      birthweight (LBW) children weighing less than 2000 g at birth who were without
      major handicaps, and a random sample of 131 normal birthweight (NBW) children
      born at term weighing over 3000 g. MAIN OUTCOME MEASURES: Validated
      questionnaires addressing behaviour completed by mothers and teachers and child
      evaluation by child psychiatrist using a semistructured interview. RESULTS:
      Behavioural problems, as defined by abnormal scores on more than four of 32
      measures, were found in 40% of LBW children compared with 7% of NBW children
      (odds ratio (OR) 8.2, 95% confidence interval (CI) 3 to 25, p = 0001). A
      psychiatric disorder was diagnosed in 27% of the LBW children compared with 9% of
      the NBW children (OR 3.1, 95% CI 1.5 to 6.5, p = 0.001). The LBW children were
      more often inattentive, had social problems, and low self esteem. None of the pre
      , neo-, or peri-natal variables in the LBW group were statistically significant
      predictors of behavioural outcomes or the presence of psychiatric disorders.
      Behavioural problems and psychiatric disorders were as common in those with birth
      weight less than 1500 g as those with birth weight 1500-2000 g. CONCLUSION: An
      increased risk of behavioural problems and psychiatric disorders persists in LBW
      adolescents.

PMID- 12193522
TI  - Bone mineralisation in premature infants cannot be predicted from serum alkaline
      phosphatase or serum phosphate.
AB  - BACKGROUND: The bone mineral content of premature infants at term is lower than
      in mature infants at the same postconceptional age. Serum alkaline phosphatase
      and serum phosphate are often used as indicators of bone mineralisation.
      OBJECTIVE: To analyse the association between bone mineral content and serum
      alkaline phosphatase and serum phosphate. METHODS: Serum alkaline phosphatase and
      phosphate were measured at weekly intervals during admission in 108 premature
      infants of gestational age below 32 weeks (mean (SD) gestational age 29 (2)
      weeks; mean (SD) birth weight 1129 (279) g). Bone mineral content was measured at
      term (mean gestational age 41 weeks) by dual energy x ray absorptiometry and
      corrected for body size. RESULTS: Serum alkaline phosphatase was significantly
      negatively associated with serum phosphate (p < 0.001). Bone mineral content was
      not associated with mean serum alkaline phosphatase (p = 0.8), peak serum
      alkaline phosphatase (p = 0.5), or mean serum phosphate (p = 0.2) at term.
      CONCLUSION: Routine measurements of serum alkaline phosphatase and serum
      phosphate are of no use in predicting bone mineralisation outcome in premature
      infants.

PMID- 12193523
TI  - A comparison of transcutaneous bilirubinometers: SpectRx BiliCheck versus Minolta
      AirShields.
AB  - BACKGROUND: Two devices are available for making transcutaneous estimates of
      serum bilirubin (SBR): the Minolta AirShields JM102 and the new SpectRx
      BiliCheck. OBJECTIVES: (a) To measure how well the readings produced by these
      devices agree with SBR measured in the laboratory; (b) to estimate for each
      device, the proportion of infants with clinical jaundice who would require blood
      sampling if the device was used as a screening tool to detect infants with SBR >
      or = 250 micromol/l. DESIGN: Prospective cohort study of jaundiced infants who
      required SBR at < or = 20 days of postnatal age. Those who had received
      phototherapy or exchange transfusion were excluded. SETTING: Tertiary neonatal
      service in South-East Scotland. INTERVENTIONS: Within 30 minutes of SBR sampling,
      transcutaneous bilirubinometry was performed using one Minolta and two SpectRx
      devices (designated A and B). RESULTS: Sixty-four neonates were enrolled, 19 of
      which were preterm (31-35 weeks). The 95% confidence intervals of a device
      reading corresponding to SBR were +/- 66.7, +/- 67.9, and +/- 66.4 micromol/l
      respectively. Using the devices to identify all SBR > or = 250 micromol/l would
      reduce SBR sampling by 23%, 16%, and 20% respectively. CONCLUSIONS: Given that
      SBR levels range from 50 to 400 micromol/l in jaundiced infants, the 95%
      confidence intervals of the devices are wide at +/- 67 micromol/l. The SpectRx
      can be used as a screening tool for hyperbilirubinaemia but there is no advantage
      in using it over the Minolta.

PMID- 12193524
TI  - Follow up of fetal outcome in cases of maternal phenylketonuria in Northern
      Ireland.
AB  - BACKGROUND: Maternal phenylketonuria (PKU) can result in multiple congenital
      anomalies. In Northern Ireland, the prevalence of PKU is relatively high at 1 in
      4000. OBJECTIVE: To assess the outcome of 39 pregnancies in 20 mothers. RESULTS:
      Dietary control was established before conception in 17 pregnancies (44%). Five
      mothers with hyperphenylalaninaemia had 11 pregnancies. There were no congenital
      anomalies in this group, and all appear to be developing normally. Fifteen women
      with classical PKU had 28 pregnancies. One pregnancy ended in a first trimester
      miscarriage. Twelve out of 27 (44%) completed pregnancies produced babies with a
      congenital anomaly and/or developmental delay. CONCLUSIONS: Most problems
      occurred when dietary control was not established until after the 2nd trimester.
      As the cohort of young women with treated PKU is growing steadily, maternal PKU
      is going to become an even greater cause for concern.

PMID- 12193526
TI  - Reduced birth weight in boys with hypospadias: an index of androgen dysfunction?
AB  - Anthropometric birth measurements analysed for 51 boys with hypospadias
      identified in a prospective cohort study showed significant reductions in mean
      values for birth weight, length, and head circumference compared with controls.
      The absence of the usual sex dimorphism for these variables suggests that the
      results represent a marker of fetal androgen dysfunction in this subgroup of
      infants.

PMID- 12193527
TI  - John Chassar Moir (1900-1977) and the discovery of ergometrine.
AB  - Chassar Moir led the research in the early 1930s that resulted in the discovery
      and identification of ergometrine, the active water soluble component of ergot of
      rye. Its use in preventing and controlling postpartum haemorrhage has saved
      countless lives in the years since. As professor of obstetrics and gynaecology in
      Oxford, he achieved distinction for his repair of vesicovaginal fistulae.

PMID- 12193525
TI  - Clinical course and medical management of neonates with severe cardiac failure
      related to vein of Galen malformation.
AB  - BACKGROUND: Neonatal presentation of vein of Galen aneurysmal malformations
      (VGAMs) with intractable cardiac failure is considered a poor prognostic sign.
      Interventional neuroradiology with embolisation has been shown to control cardiac
      failure, but there is a perception that neurological outcome in survivors is
      poor. OBJECTIVE: To determine if aggressive intensive care and anaesthetic
      management of cardiac failure before urgent embolisation can influence morbidity
      and mortality. PATIENTS: Nine newborns (four boys, five girls) were diagnosed
      with symptomatic vein of Galen malformations in the neonatal period during the
      period 1996-2001. Eight developed intractable high output cardiac failure
      requiring initial endovascular treatment in the first week of life. RESULTS: The
      immediate outcome after a series of endovascular procedures was control of
      cardiac failure and normal neurological function in six (66%) patients, one death
      from intractable cardiac failure in the neonatal period, and two late deaths with
      severe hypoxic-ischaemic neurological injury (33% mortality). Clinical review at
      6 months to 4 years of age showed five infants with no evidence of neurological
      abnormality or cardiac failure and one child with mild developmental delay (11%).
      CONCLUSIONS: Aggressive medical treatment of cardiac failure and early
      neurointervention combined with modern neuroanaesthetic care results in good
      survival rates with low morbidity even in cases of high risk VGAM presenting in
      the immediate perinatal period with cardiac failure. Systemic arterial
      vasodilators improve outcome in neonates with cardiac failure secondary to VGAM.
      Excessive beta adrenergic stimulation induced by conventional inotropic agents
      may exacerbate systemic hypoperfusion.

PMID- 12193528
TI  - Intramuscular injection of propacetamol in a neonate.

PMID- 12193529
TI  - Placement of neonatal central venous catheter tips: is the right atrium so
      dangerous?

PMID- 12193530
TI  - A novel pathway of prostacyclin signaling-hanging out with nuclear receptors.
AB  - Prostacylin (PGI(2)), one of the major prostaglandins, is derived from
      arachidonic acid by the action of the cyclooxygenase (COX) system coupled to
      PGI(2) synthase (PGIS). The presence of the COX-2/PGIS at the nuclear and
      endoplasmic reticular membrane suggests differential signaling pathways of PGI(2)
      actions involving both cell surface and nuclear receptors. Although the signaling
      of PGI(2) via its cell surface receptor, prostacyclin receptor (IP), is well
      documented in vascular biology, its action via nuclear receptors in other
      physiological responses is gradually being more appreciated. Peroxisomal
      proliferator-activated receptors (PPARs), PPARalpha, PPARgamma, and PPARdelta,
      though initially cloned as a family of orphan receptors, are now known for their
      ligand promiscuity. The ligands range from free fatty acids and their derivatives
      produced by the cyclooxygenase or lipoxygenase pathway to certain hypolipidemic
      drugs. The predisposition of PPARs to use a wide spectrum of ligands is well
      explained by their unusually large ligand-binding pocket. The promiscuous ligand
      usage by PPARs is also reflected by their involvement in various
      pathophysiological events. Several recent independent reports show that
      endogenously produced PGI(2) indeed activates PPARdelta in vivo, indicating that
      a novel signaling mechanism for this abundant eicosanoid is operative in certain
      systems. This review attempts to cover recent developments in nuclear actions of
      PGI(2) in diverse biological functions.

PMID- 12193531
TI  - Does circulating leptin have the ability to cross the blood-brain barrier and
      target neurons directly?

PMID- 12193532
TI  - Glucose-regulated proinsulin gene expression is required for adequate insulin
      production during chronic glucose exposure.
AB  - Psammomys obesus, an animal model of type 2 diabetes, shows rapid and marked
      depletion of pancreatic insulin content as hyperglycemia develops when fed a high
      calorie diet. P. obesus islets do not increase proinsulin gene expression when
      exposed to high glucose, which may be related to absence of the conserved form of
      the transcription factor insulin promoter factor 1/pancreatic-duodenal homeobox
      1. The present study assesses the importance of regulation of proinsulin gene
      expression by glucose for insulin production. Islets of diabetes-prone P. obesus
      and diabetes-resistant Wistar rats, cultured at various glucose concentrations
      for up to 24 h, were analyzed for proinsulin mRNA by quantitative RT-PCR,
      proinsulin biosynthesis by leucine incorporation into proinsulin, and insulin
      content and secretion by RIA. No increase in proinsulin mRNA was observed in P.
      obesus islets during 24-h exposure to increasing concentrations of glucose. In
      contrast, rat islets exposed to high glucose responded with a 2- to 3-fold
      stimulation of proinsulin mRNA. The failure of P. obesus islets to increase
      proinsulin mRNA was accompanied by a reduced proinsulin biosynthetic response:
      after 24 h, maximal proinsulin biosynthesis was blunted, associated with
      depletion of islet insulin content. Inhibition of glucose-stimulated proinsulin
      gene transcription in rat islets by actinomycin D did not affect the early
      proinsulin biosynthetic response, which, however, was reduced to the level of P.
      obesus islets after 24 h in culture. We conclude that stimulation of proinsulin
      gene transcription by glucose is necessary for maintaining proinsulin
      biosynthesis and hence conserving pancreatic insulin stores, under conditions of
      sustained secretory drive, but not for short-term regulation of proinsulin
      biosynthesis Our findings support the hypothesis that inadequate regulation of
      proinsulin gene expression by glucose contributes to the failure of P. obesus to
      cope with the increased demand for insulin associated with caloric excess,
      leading to depletion of insulin stores and diabetes.

PMID- 12193533
TI  - Activation of the MAPK pathway enhances sensitivity of MCF-7 breast cancer cells
      to the mitogenic effect of estradiol.
AB  - Long-term estrogen deprivation causes human breast cancer cells to develop
      hypersensitivity to the mitogenic effect of estradiol (E(2)). Our prior studies
      demonstrated an association between enhanced MAPK activation and hypersensitivity
      in long-term estrogen-deprived (LTED) MCF-7 cells. Herein, we report that MAPK is
      constitutively activated in LTED cells and not dependent on serum factors.
      Additionally, activated MAPK levels fall upon reversion of the hypersensitivity.
      Importantly, we now provide direct evidence that enhanced MAPK causes
      hypersensitivity to E(2). We activated MAPK in wild-type MCF-7 cells using
      TGFalpha, and demonstrated a 2-3 log enhancement of sensitivity to E(2). PD98059
      abrogated the TGFalpha-induced effect, indicating that MAPK activation is
      responsible for E(2) hypersensitivity. To determine the level at which MAPK
      activation enhanced E(2) sensitivity, we examined the dose-response effects of
      E(2) on several transcriptional readouts, including ERE-reporter activity and the
      levels of progesterone receptor and pS2. Wild-type and LTED cells exhibited
      nearly identical responses to E(2), suggesting that mechanisms downstream of
      estrogen receptor-mediated transcription are involved in inducing
      hypersensitivity. In support of this possibility, LTED and TGFalpha-treated wild
      type cells were hypersensitive to the effects of E(2) on the key cell cycle
      regulator, E2F1.

PMID- 12193534
TI  - Abnormal bone architecture and biomechanical properties with near-lifetime
      treatment of rats with PTH.
AB  - Skeletal effects are described for near-lifetime treatment of young, female rats
      with recombinant human PTH (1-34) (PTH). Rats (5-8 wk of age) were administered
      0, 5, 30, or 75 microg/kg x d sc PTH for up to 2 yr, as part of an oncogenicity
      evaluation, which is required by regulatory agencies for potential chronic
      therapies. Proliferative lesions were observed in the skeleton as described in
      Vahle et al. (1 ); in this paper, we describe the quantitative bone data for this
      study. In the appendicular skeleton, PTH stimulated trabecular and endocortical
      mineral apposition to the near exclusion of marrow spaces at 5 microg/kg, with
      some periosteal apposition at 30 microg/kg, followed by considerable periosteal
      apposition and altered geometry at 75 microg/kg. Increased bone mass was observed
      for all treatment groups that substantially exceeded normal levels attained by
      vehicle controls and exceeded skeletal efficacy reported previously for similar
      doses in shorter-term studies. Dose-dependent increases in osteocalcin levels and
      a linear increase in wet weight of femora were observed for the entire treatment
      duration, suggesting nearly continuous PTH stimulation of osteoblasts and
      skeletal growth throughout life. Histology showed many osteocytes and prominent
      osteoblasts, but a conspicuous absence of osteoclasts. Morphometry showed a lack
      of distinction between trabecular and cortical bone. Biomechanics of vehicle
      controls showed that optimal mechanical integrity for the normal skeleton is
      observed at about 11 months of age. PTH greatly strengthened and stiffened
      vertebra and femora; however, the midshaft showed reduced toughness and increased
      brittleness with treatment, which was not the case for vertebra. Related studies
      of 6 and 9 months duration showed that the optimal duration for PTH skeletal
      efficacy was about 6 months in rats, based on toughness, strength, ultimate
      displacement, and architecture, especially for cortical bone. Therefore,
      treatment duration is an under appreciated aspect of PTH pharmacology; and PTH
      skeletal effects are a complex function of dose and duration. Comparative
      analyses showed that short-term treatment (6 months or less) is more advantageous
      than near-lifetime treatment, because PTH stimulates skeletal growth throughout
      life, resulting in abnormal architecture and untoward biomechanical properties in
      rats.

PMID- 12193535
TI  - GnRH pulse frequency modulation of gonadotropin subunit gene transcription in
      normal gonadotropes-assessment by primary transcript assay provides evidence for
      roles of GnRH and follistatin.
AB  - We examined the time course of action of GnRH pulse frequency on gonadotropin
      subunit gene transcription and assessed the roles of GnRH, follistatin (FS), and
      activin on differential transcription of the LHbeta and FSHbeta genes. GnRH
      deficient male rats were pulsed with 25 ng GnRH either every 30 min (fast
      frequency) or every 240 min (slow frequency) for 1-24 h. Both GnRH frequencies
      increased alpha primary transcript (PT) 5-fold within 6 h, but only fast
      frequency GnRH increased alpha mRNA. Only fast frequency GnRH pulses affected
      LHbeta PT, resulting in 6- to 9-fold increases between 1-24 h. Fast frequency
      GnRH pulses transiently increased FSHbeta PT at 1 and 6 h (4- and 2-fold,
      respectively); but by 24 h FSHbeta PT had returned to control levels and was
      correlated to a 5- to 9-fold increase in FS mRNA. In contrast, slow GnRH pulses
      increased FSHbeta PT 3- and 6-fold at 8 and 24 h, respectively, which was
      correlated with a decline in FS mRNA. Activin mRNA did not change significantly
      after either GnRH frequency, but tended to fall after fast pulses. To test
      whether activin was required for the effects of GnRH on FSHbeta transcription,
      rats were treated with GnRH pulses every 240 min for 8 h +/- FS. FS treatment
      alone markedly decreased basal FSHbeta PT. GnRH in the presence of FS increased
      FSHbeta PT 8-fold but did not restore FSHbeta transcription to control or GnRH
      alone values. In summary, whereas alpha-subunit transcription is independent of
      frequency, an increase in alpha mRNA requires fast frequency GnRH pulses. Fast
      frequency GnRH pulses increased both LHbeta and FSHbeta transcription, but the
      response of FSHbeta was transient. The sustained rise in FSHbeta transcription
      and mRNA expression required slow frequency GnRH pulses and was correlated to low
      FS mRNA. Neutralization of pituitary activin by exogenous FS markedly reduced
      basal FSHbeta PT and mRNA but did not prevent the stimulation of FSHbeta
      transcription by slow frequency GnRH pulses. These studies suggest that the
      frequency regulation of FSHbeta transcription involves both direct actions of
      GnRH and indirect effects, via changes in pituitary FS expression.

PMID- 12193536
TI  - Dehydroepiandrosterone modulates nuclear factor-kappaB activation in hippocampus
      of diabetic rats.
AB  - Oxidative stress induced by chronic hyperglycemia contributes to cerebrovascular
      complications in diabetes. Reactive oxygen species activate the transcription
      factor nuclear factor-kappaB (NF-kappaB), which in turn activates a variety of
      target genes linked to the development of diabetic complications.
      Dehydroepiandrosterone, an adrenal steroid, which possesses a multitargeted
      antioxidant effects, is also synthesized de novo by the brain. Normoglycemic and
      streptozotocin-diabetic rats were either treated with dehydroepiandrosterone
      (DHEA) for 7, 14, or 21 d (4 mg/d per rat) or left untreated. Oxidative state,
      antioxidant balance and activation of nuclear transcriptional redox-sensitive
      factor NF-kappaB were evaluated in the hippocampus area. In streptozotocin
      treated rats, besides the strong increase in oxygen reactive species, there is
      also a persistent activation of NF-kappaB. The derangement of the oxidative
      balance in the brain induced by diabetes improves with DHEA. Moreover, DHEA
      completely counteracts NF-kappaB activation, measured as DNA binding activity,
      and hinders the increase of IkappaB-alpha inhibitory subunit induced by oxidative
      stress. The time-lag of DHEA's effects on NF-kappaB activation parallels its
      effects on oxidative balance. Results indicate that DHEA might protect
      hippocampus from chronic activation of NF-kappaB-dependent genes by reducing NF
      kappaB nuclear translocation. This could result in protection from diabetes
      dependent brain damage.

PMID- 12193538
TI  - Ghrelin stimulates GH but not food intake in arcuate nucleus ablated rats.
AB  - Ghrelin, an endogenous ligand for the GH secretagogue receptor 1a (GHS-R(1a)),
      was originally purified from the rat stomach. Ghrelin mRNA and peptide have also
      been detected in the hypothalamus and pituitary. Ghrelin is a novel acylated
      peptide that regulates GH release and energy metabolism. GHS-R(1a) mRNA is
      expressed in the pituitary gland as well as in several areas of the brain
      including the hypothalamus. In this study, we examined whether ghrelin could
      stimulate GH secretion and feeding in chronic GHRH, neuropeptide Y, and agouti
      related protein deficient rats that were neonatally treated with monosodium
      glutamate (MSG), which destroys the neurons in the hypothalamic arcuate nucleus
      (ARC). Intravenous (iv) administration of rat ghrelin (10 micro g/kg body weight)
      increased plasma GH levels significantly in the normal adult male rats during a
      GH trough period of pulsatile GH secretion, while iv injection of ghrelin in MSG
      treated rats resulted in a markedly attenuated GH response. When rat ghrelin (10
      micro g/rat) was administered intracerebroventricular (icv), plasma GH levels
      were increased comparably in normal control and MSG-treated rats. However, the GH
      release after icv injection of ghrelin was markedly diminished compared with that
      after iv administration of a small amount of ghrelin in normal control rats (icv:
      10 micro g/rat, iv: approximately 4.0 micro g/rat), indicating that the GH
      releasing activity of exogenous ghrelin is route dependent and at least in part
      via hypothalamic ARC. The icv administration of 1 micro g of ghrelin increased
      significantly 4-h food intake in normal control, whereas the peptide did not
      increase food intake in MSG-treated rats, indicating that the feeding response to
      ghrelin requires intact ARC. Taken together, the primary action of ghrelin on
      appetite control and GH releasing activity is via the ARC even though it might
      act on another type of GHS-R besides GHS-R(1a).

PMID- 12193537
TI  - Functional insulin receptors on human epithelial ovarian carcinoma cells:
      implications for IGF-II mitogenic signaling.
AB  - The insulin receptor mediates a proliferative response in certain transformed
      cells, but little is known about its function in ovarian cancer. We used human
      epithelial ovarian carcinoma cell lines and lifespan-extended normal ovarian
      surface epithelial (OSE) cells to examine (125)I-insulin binding and mitogenic
      responses to insulin. All cancer cell and OSE cultures specifically bound (125)I
      insulin. Except for OV202, the carcinoma lines had elevated insulin binding
      compared with OSE cells. All carcinoma lines except OV202 expressed insulin
      receptor as detected by flow cytometry and increased (3)H-thymidine incorporation
      or cell number in response to 0.1-10 nM insulin. Interestingly, similar
      concentrations of IGF-II also induced proliferation of the insulin-responsive
      cancer cell lines and displaced (125)I-insulin binding. Direct binding of (125)I
      IGF-II to the insulin receptor was visualized by cross-linking and
      immunoprecipitation. Binding of IGF-II to the insulin receptor and a
      proliferative effect of insulin suggest the presence of insulin receptor isoform
      A. Real-time PCR analyses confirm that insulin receptor isoform A expression
      predominates over isoform B expression in the ovarian carcinoma cell lines. This
      report suggests that the insulin receptor may play a role in the regulation of
      ovarian cancer cell growth.

PMID- 12193539
TI  - Cyclooxygenase 2 pathway mediates IL-1beta regulation of IL-1alpha, -1beta, and
      IL-6 mRNA levels in Leydig cell progenitors.
AB  - Prostanoids are arachidonic acid (AA) metabolites derived from the cyclooxygenase
      (COX1 and COX2 isozymes) pathway and are involved in signal transduction pathways
      activated by distinct ILs. Although COX1 is the constitutive isoform of COX, IL
      1beta is a potent inducer of COX2 expression in distinct cell types. This study
      was designed to determine whether cyclooxygenases could mediate endogenous
      cytokine regulation in rat progenitor Leydig cells. COX and IL (IL-1alpha, IL
      1beta, and IL-6) mRNAs were measured by PCR and real-time PCR analyses,
      respectively. COX function was assessed using COX activity inhibitors:
      indomethacin (INDO; COX1 and COX2 inhibitor) and NS-398 (COX2 selective
      inhibitor). Our data indicate that endogenous progenitor COX1 mRNA levels are low
      and are not regulated by IL-1beta. In contrast, COX2 mRNA is induced by IL-1beta
      at 6, 9, and 24 h. IL-1beta induction of IL mRNAs was in part significantly
      impaired in the presence of INDO or NS-398. Among the prostanoids tested,
      prostaglandin E(2) (PGE(2)), PGF(2alpha), and carbaprostacyclin reversed the INDO
      inhibition of IL production. PGs alone have no (IL-1alpha and IL-1beta) or a
      modest (IL-6) effect on IL mRNA levels. PGE(2), PGF(2alpha), and PGI(2)
      measurements show that IL-1beta treatment significantly increases progenitor
      Leydig cell production of these PGs. Taken together, our data demonstrate that
      this COX2 cascade is a regulator of cytokines in Leydig progenitors.

PMID- 12193540
TI  - Stimulation of hepatic signal transducer and activator of transcription 5b by GH
      is not altered by 3-methylcholanthrene.
AB  - We are investigating the mechanisms by which aromatic hydrocarbons, such as 3
      methylcholanthrene (MC), suppress hepatic cytochrome P450 2C11 (CYP2C11) gene
      expression. CYP2C11 is an enzyme expressed in the liver of male rats and is
      regulated by a pulsatile pattern of GH secretion. We have previously shown that
      MC attenuates the stimulatory effect of GH on CYP2C11 expression in
      hypophysectomized male rats. In follow-up studies we evaluated the effect of MC
      on GH-stimulated signal transducer and activator of transcription 5b (STAT5b)
      phosphorylation, nuclear translocation, and DNA-binding activity. GH-stimulated
      increases in hepatic nuclear STAT5b and phospho-STAT5b levels were not different
      between groups of hypophysectomized rats receiving MC or vehicle. This
      observation was corroborated at the DNA-binding level by EMSA. We also measured
      GH-induced STAT5b activation in the H4IIE rat hepatoma cell line. STAT5b DNA
      binding activity detected in GH-treated cells was not affected by MC.
      Immunocytochemistry experiments revealed no effect of MC on GH-stimulated STAT5b
      nuclear translocation in H4IIE cells. These in vivo and in vitro data suggest
      that interference with GH-stimulated STAT5b activation does not constitute a
      mechanism by which MC attenuates the stimulatory effect of GH on CYP2C11 gene
      expression.

PMID- 12193541
TI  - The transcription factor basic transcription element-binding protein 1 is a
      direct thyroid hormone response gene in the frog Xenopus laevis.
AB  - Several genes have been identified that are activated or repressed by thyroid
      hormone in tadpole tissues during metamorphosis of the frog Xenopus laevis. One
      rapidly and strongly induced gene encodes the Xenopus homolog of basic
      transcription element-binding protein 1 (xBTEB1), an SP1-related transcription
      factor. xBTEB1 has similar DNA-binding activity and transcriptional activation
      properties as mammalian BTEB1. The thyroid hormone-dependent regulation of xBTEB1
      was investigated using a modified electrophoretic mobility shift assay to scan
      genomic DNA for receptor-binding sites. Due to the tetraploid X. laevis genome,
      xBTEB1 is duplicated, and thyroid hormone regulates both copies. A consensus
      thyroid hormone response element (TRE) lies far upstream of the transcriptional
      start site of both genes. The TRE is nested within a 200-bp region of high
      sequence conservation between these two genes that duplicated millions of years
      ago. The TRE acts as a strong response element in transfection assays using a
      heterologous promoter or its native context. Thus, one of the earliest thyroid
      hormone-induced genes in tadpoles is a transcription factor regulated through an
      evolutionarily conserved TRE. xBTEB1 is predicted to play an important role in
      downstream gene regulation leading to the growth and remodeling of tissues at
      metamorphosis.

PMID- 12193542
TI  - Hepatocyte growth factor/scatter factor facilitates migration of GN-11
      immortalized LHRH neurons.
AB  - The molecular cues regulating the migratory process of LHRH neurons from the
      olfactory placode into the brain are not well known, but gradients of chemotropic
      and chemorepellent factors secreted by the targets are likely to play a key role
      in guidance mechanisms. Hepatocyte growth factor/scatter factor (HGF/SF) is a
      pleiotropic cytokine inducing cell migration. It is involved in a variety of
      developmental processes through interaction with its receptor c-Met. Here we show
      that c-Met-antibody labels LHRH migrating neurons in the olfactory mesenchyme of
      E12 mouse and analyze the potential chemotropic effect of HGF/SF on two
      immortalized LHRH cell lines, GT1-7 and GN11, isolated from tumors developed in
      the hypothalamus and in the olfactory bulb, respectively. By RT-PCR analysis,
      Western blotting, and immunocytochemistry, we provide evidence for a high level
      of c-Met expression in GN11, but not in GT1-7, cells. In addition, HGF/SF
      treatment promotes specific migratory activity of GN11 cells, as demonstrated by
      collagen gel assay, time-lapse video microscopy, and Boyden's chamber
      experiments. Such promotion is inhibited by the neutralizing antibody. The data
      reported here represent the first direct evidence of a chemotactic effect of
      HGF/SF on immortalized LHRH neurons.

PMID- 12193543
TI  - FSH and TGF-beta superfamily members regulate granulosa cell connective tissue
      growth factor gene expression in vitro and in vivo.
AB  - Connective tissue growth factor (CTGF) is a heparin-binding growth factor
      implicated in diverse epithelial cell types as a paracrine regulator of mitosis,
      angiogenesis, cellular taxis, and remodeling of the extracellular matrix. To
      understand the possible roles of CTGF in the ovarian paracrine system, we studied
      CTGF gene expression by granulosa cells in relation to their stage of cellular
      differentiation using both in vitro and in vivo methodologies. Untreated
      monolayer granulosa cell cultures from immature rats abundantly expressed the
      approximately 2.5-kb CTGF mRNA transcript (determined by Northern analysis), but
      had low levels of aromatase activity (an index of granulosa cell
      differentiation). Treatment for 48 h with FSH (0.1-10 ng/ml) dose-dependently
      inhibited (>or=50%) CTGF mRNA expression, but enhanced aromatase enzyme activity.
      This in vitro observation of CTGF mRNA down-regulation coinciding with FSH
      induced granulosa cell maturation is substantiated by studies of in vivo ovarian
      CTGF expression in FSHbeta knockout mice. Northern blot and in situ hybridization
      analyses demonstrate high levels of CTGF expression in the granulosa cells of
      preantral follicles blocked from further development by the absence of FSH. The
      action of FSH (10 ng/ml) was mimicked in vitro by 8-bromo-cAMP (1.0 mM) and was
      augmented by the additional presence of androgen (1 micro M 5alpha
      dihydrotestosterone), consistent with mediation by intracellular cAMP.
      Conversely, treatment of granulosa cell cultures with TGFbeta1 (0.1-10 ng/ml)
      dose-dependently increased CTGF mRNA levels up to 12-fold at a dose of 10 ng/ml,
      without affecting aromatase activity. Cotreatment with FSH (0.1-10 ng/ml) dose
      dependently suppressed the stimulatory action of TGFbeta1 (10 ng/ml) on CTGF
      mRNA, but substantially enhanced aromatase activity beyond levels induced by FSH
      alone. Importantly, other TGFbeta superfamily members known to be produced in the
      ovary (growth/differentiation factor-9 and activin A; 10 ng/ml) stimulated
      granulosa cell CTGF mRNA in a similar fashion as TGFbeta1 (10 ng/ml), and this
      was also inhibited by FSH (10 ng/ml). These data show that granulosa cell CTGF
      gene expression is inversely related to the stage of granulosa cell
      differentiation, being directly inhibited by FSH via cAMP-mediated signaling.
      CTGF mRNA abundance in nondifferentiated granulosa cells is up-regulated in vitro
      by TGFbeta1, growth/differentiation factor-9, and activin, suggesting paracrine
      roles for these growth/differentiation factors in the regulation of CTGF
      synthesis in mammalian ovaries.

PMID- 12193544
TI  - Increasing triglyceride synthesis inhibits glucose-induced insulin secretion in
      isolated rat islets of langerhans: a study using adenoviral expression of
      diacylglycerol acyltransferase.
AB  - The mechanisms by which prolonged exposure to elevated levels of fatty acids (FA)
      adversely affects pancreatic beta-cell function remain unclear. Studies in the
      Zucker diabetic fatty rat have suggested that excessive accumulation of
      triglycerides (TG) in islets plays a key role in the deleterious effects of FA.
      However, a direct relationship between TG accumulation and defective beta-cell
      function has not been established. The aim of the present study was therefore to
      determine whether increasing TG synthesis in isolated rat islets of Langerhans
      impairs insulin secretion. To this end, we infected isolated rat islets with an
      adenovirus encoding for the enzyme catalyzing the last step of triglyceride
      synthesis, acyl-coenzyme A:diacylglycerol acyltransferase 1 (DGAT). DGAT
      overexpression did not modify glucose oxidation nor palmitate oxidation, but
      increased palmitate incorporation into triglycerides by approximately 2-fold.
      Islets overexpressing DGAT and cultured in elevated glucose levels for 72 h had
      markedly impaired insulin secretion in response to glucose, but responded
      normally to the nonglucose secretagogues glyburide and potassium chloride. The
      deleterious effects of DGAT overexpression were not additive to those of
      prolonged exposure to palmitate. We conclude that a selective increase in TG
      content impairs glucose-induced insulin secretion, a mechanism likely to mediate,
      at least in part, the deleterious effects of FA on pancreatic beta-cell function.

PMID- 12193545
TI  - Hormone-sensitive lipase deficiency in mice causes lipid storage in the adrenal
      cortex and impaired corticosterone response to corticotropin stimulation.
AB  - Hormone-sensitive lipase (HSL, E.C.3.1.1.3, gene designation Lipe) is reportedly
      the major cholesteryl esterase of adrenal cortex. Because of the potential
      importance of cholesteryl ester hydrolysis in steroidogenesis, gene-targeted HSL
      deficient mice were assessed for adrenal cortical morphology and function.
      Compared with control animals, HSL deficiency results in a marked accumulation of
      lipid droplets both in zona glomerulosa and zona fasciculata. In the zona
      fasciculata, lipid accumulation was observed progressively from the outer to the
      inner regions, culminating near the corticomedullary junction with the formation
      of syncytial-lipoid structures having the appearance of degenerative cells. These
      morphological changes did not significantly alter the basal levels of circulating
      corticosterone, but following ACTH stimulation, corticosterone levels were
      decreased (P < 0.001). The observation of normal basal corticosterone and
      aldosterone levels demonstrates that some free cholesterol for steroid synthesis
      can be produced independently of HSL. Taken together, these results indicate that
      HSL-deficient mice accumulate lipid droplets in such a way as to impair acute
      ACTH stimulation of corticosterone secretion. Such observations are also found in
      some forms of congenital adrenal hyperplasia. By extension, HSL deficiency may be
      a cause of hereditary adrenocortical hypofunction in humans.

PMID- 12193546
TI  - Delayed short-term secretory regulation of ghrelin in obese animals: evidenced by
      a specific RIA for the active form of ghrelin.
AB  - Ghrelin is an acylated peptide, whose lipid modification is essential for its
      biological activities. Previous studies demonstrated that it strongly stimulates
      GH release and has a potent orexigenic action. Meanwhile, there is enough
      evidence showing that feeding states influence plasma ghrelin levels. Fasting
      stimulates ghrelin secretion, and feeding reduces plasma ghrelin levels. In this
      study we examined the regulation of plasma ghrelin by fasting in genetically
      obese animals considering its molecular forms. Plasma levels of active form of
      ghrelin as well as those of total ghrelin were reduced in ob/ob and db/db mice
      compared with those in their control mice. Zucker fatty (fa/fa) rats also showed
      lower plasma ghrelin levels by fasting than the control rats. Insulin-induced
      hypoglycemia, however, stimulated ghrelin secretion in the fasted fatty rats.
      Moreover, glucose injection was revealed to reduce plasma ghrelin levels in rats.
      The effect of the severity of obesity on secretory regulation of ghrelin was also
      studied. Older fatty rats showed low plasma ghrelin levels even after 48-h
      fasting. These data suggest that the short-term secretory regulation of total
      ghrelin and the active form of ghrelin is delayed in obese animals and that blood
      glucose levels may be involved in the delayed regulation.

PMID- 12193547
TI  - Mullerian inhibiting substance blocks the protein kinase A-induced expression of
      cytochrome p450 17alpha-hydroxylase/C(17-20) lyase mRNA in a mouse Leydig cell
      line independent of cAMP responsive element binding protein phosphorylation.
AB  - Mullerian inhibiting substance (MIS) is produced by fetal Sertoli cells and
      causes regression of the Mullerian duct in male fetuses shortly after commitment
      of the bipotential embryonic gonad to testes differentiation. MIS is also
      produced by the Sertoli cells and granulosa cells of the adult gonads where it
      plays an important role in regulating steroidogenesis. We have previously shown
      that MIS can dramatically reduce testosterone synthesis in Leydig cells by
      inhibiting the expression of cytochrome P450 17alpha-hydroxylase/C(17-20) lyase
      (Cyp17) mRNA in vitro and in vivo. To characterize the signal transduction
      pathway used by MIS to control expression of endogenous Cyp17 in a mouse Leydig
      cell line, we demonstrate that MIS inhibits both LH- and cAMP-induced expression
      of Cyp17 at concentrations as low as 3.5 nM and for as long as 18 h. The
      induction of steroidogenic acute regulatory protein (StAR) mRNA by cAMP, however,
      was slightly increased by addition of MIS. Protein kinase A (PKA) inhibition with
      H-89 blocked Cyp17 mRNA induction, suggesting that MIS interferes with the PKA
      signal transduction pathway. Inhibition of Cyp17 induction was not seen with
      added U0126, and wortmannin inhibited the induction incompletely. In addition,
      phosphorylation of the cAMP responsive element binding protein (CREB) was not
      detected following 50 micro M cAMP exposure, a concentration sufficient for Cyp17
      mRNA induction. Moreover, CREB phosphorylation, which was observed with addition
      of 500 micro M cAMP, was not inhibited by coincubation with MIS. Taken together,
      these results suggest that cAMP induces expression of Cyp17 by a PKA-mediated
      mechanism and that this induction, which is inhibited by MIS signal transduction,
      does not require CREB activity, and is distinct from that used to induce
      steroidogenic acute regulatory protein expression.

PMID- 12193548
TI  - Regulation of microsomal P450, redox partner proteins, and steroidogenesis in the
      developing testes of the neonatal pig.
AB  - Testicular growth and plasma androgen concentrations increase markedly in the
      first weeks of neonatal life of pigs. The regulation of steroidogenesis through
      this period was examined by measuring total microsomal cytochromes P450 (P450),
      17alpha-hydroxylase/17,20-lyase P450 (P450c17) and aromatase P450 (P450arom)
      enzyme activities, and the redox partner proteins nicotinamide adenine
      dinucleotide phosphate, reduced form (NADPH)-cytochrome P450 reductase
      (reductase) and cytochrome b(5) in testicular microsomes. Testes were collected
      from 1-24 d of age, and testicular development was suppressed by a GnRH
      antagonist in some animals from d 1-14. Both 17/20-lyase and aromatase activities
      increased from d 1-7 but not thereafter, and 17-20-lyase activity was always at
      least 200-fold higher than aromatase activity. Reductase decreased in wk 1, then
      increased to d 24. No changes were seen in cytochrome b(5) expression. GnRH
      antagonist treatment suppressed plasma LH, testosterone and testes growth to d
      14. 17,20-Lyase and aromatase activities in testicular microsomes were reduced by
      20% and 50%, respectively. Total microsomal P450 concentration was reduced by 50%
      on d 7, but there was no effect of treatment on reductase or cytochrome b(5)
      expression. These data support the hypothesis that the rise in neonatal
      testicular androgen secretion is more likely due to gonadotropin-stimulated
      gonadal growth, rather than specific P450c17 expression. Neither P450c17 nor
      P450arom can account for the decline in total microsomal P450. Reductase and
      cytochrome b(5) expression appears to be constitutive, but reductase levels
      saturate both P450c17 and P450arom.

PMID- 12193549
TI  - Transcriptional repression of the rat osteocalcin gene by deltaEF1.
AB  - Intron I of the rat osteocalcin gene contains silencer elements that suppress
      osteocalcin-reporter fusion gene transcription. The consensus sequence for the
      transcription factor deltaEF1 is homologous to two pyrimidine-rich repeats in
      intron 1 that contribute to silencing of osteocalcin-reporter fusion genes. To
      assess if overexpression of deltaEF1 augments transcriptional repression by these
      sequences, the intron 1 sequences (wtS) were placed upstream to the native rat
      osteocalcin promoter fused to a luciferase reporter gene (-306-OCluc).
      Coexpression of the wtS-(-306-OCluc) fusion gene with deltaEF1 decreased
      luciferase activity 30% relative to cotransfection with empty vector. Repression
      was abolished by point mutations in the putative deltaEF1 motifs, mS-(-306
      OCluc). To determine whether deltaEF1 binds to these DNA sequences, gel
      retardation assays were performed using oligonucleotides containing the putative
      osteocalcin deltaEF1 motifs and a classical deltaEF1 motif, as radiolabeled
      probes. A comigrating DNA-protein complex generated by these probes was
      recognized by an antibody directed against deltaEF1 and competed for by excess
      unlabeled wild-type oligonucleotides. Oligonucleotides with mutations in the
      osteocalcin sequences, which abolish suppression, and in the deltaEF1 consensus
      site, that abolishes binding to deltaEF1, were unable to compete for the
      formation of this complex. Overexpression of deltaEF1 in ROS 17/2.8 cells led to
      an 84% decrease in osteocalcin mRNA levels relative to cells transfected with
      empty vector, confirming that deltaEF1 suppresses expression of the endogenous
      osteocalcin gene.

PMID- 12193550
TI  - G protein-coupled receptor 30 is critical for a progestin-induced growth
      inhibition in MCF-7 breast cancer cells.
AB  - The issue of how progesterone affects mammary gland growth is controversial, and
      the mechanism governing the effects of the hormone remains mostly unknown. We
      have previously shown that G protein-coupled receptor 30 (GPR30) is a progestin
      target gene whose expression correlates with progestin-induced growth inhibition
      in breast cancer cells. In this study, we investigate the role of GPR30 in
      regulating cell proliferation and mediating progestin-induced growth inhibition.
      When progestin failed to inhibit the growth of MCF-7 cells and instead stimulated
      growth, GPR30 was down-regulated. In this way, the inhibitory or stimulatory
      affects that progestin has on proliferation correlated with the level of
      expression of GPR30. Transient expression of GPR30 resulted in a marked
      inhibition of cell proliferation independent of estrogen treatment. GPR30
      antisense was used to evaluate the role of GPR30 expression in progestin-induced
      growth inhibition. A diminished GPR30 mRNA expression by the antisense stimulated
      growth. Interestingly, GPR30 antisense abrogated the growth inhibitory effect of
      progestin and progesterone. Indeed, progestin induced 1) a reduction in cell
      proliferation, 2) G1-phase arrest, and 3) down-regulation of cyclin D1 was
      diminished. These data suggest that the orphan receptor, GPR30, is important for
      the inhibitory effect of progestin on growth.

PMID- 12193551
TI  - Inhibition of recovery of spermatogenesis in irradiated rats by different
      androgens.
AB  - We previously showed that exogenous testosterone (T) inhibited GnRH-antagonist
      stimulated spermatogenic recovery in irradiated rats through an androgen-receptor
      mediated action. In the present study, we tested whether the inhibition is
      attributable to T, a specific androgenic metabolite of T, or a general property
      of androgens in this system. In addition, we also tested whether estradiol-17beta
      (E2), a metabolite of T, is similarly inhibitory. Rats irradiated with 5 Gy were
      treated with a GnRH antagonist during wk 3-7. Neither irradiation nor GnRH
      antagonist treatment produced biologically significant changes in the relative
      intratesticular levels of several androgenic metabolites. Next, groups of rats,
      irradiated and treated with GnRH antagonist as above, were given various doses of
      one of the following androgens: T, 5alpha-dihydrotestosterone, 7alpha-methyl-19
      nortestosterone, methyltrienolone, or E2. The percentage of tubules showing
      differentiation (tubule differentiation index) was increased to 68% by the GnRH
      antagonist, from a value of 0.1% in irradiated-only rats at 13 wk after
      irradiation. All of the added androgens inhibited spermatogenic recovery,
      lowering the tubule differentiation index to between 0.4-36%, but no inhibition
      was observed with the addition of E2. Of all the androgen treatments tested, T
      (given as daily injections of T propionate) minimally inhibited spermatogenic
      recovery while maintaining androgen-responsive tissue weights, and might be most
      useful in clinical studies. Hormonal measurements in androgen-treated rats were
      most consistent with the androgen inhibition of spermatogenic recovery in
      irradiated rats being a combined result of a direct inhibitory effect of all
      androgens on the testis and an indirect effect through the pituitary by raising
      levels of FSH, which seems to add to the inhibition of spermatogenic recovery.

PMID- 12193552
TI  - A novel promoter is involved in the expression of estrogen receptor alpha in
      human testis and epididymis.
AB  - The role of estrogens in the development and physiology of the male reproductive
      tract remains provocative, with a growing body of evidence suggesting that
      estrogens are able to influence normal testis development and physiology, through
      their classical receptors, estrogen receptor (ER)-alpha and ER-beta. We describe
      the identification and characterization of a new promoter that is involved in the
      expression of ER-alpha in the epididymis and in testis. This promoter lies on
      chromosome 6q25.1, approximately 16 kb upstream of the first coding exon of ER
      alpha. Sequence analysis indicates that this promoter has a conventional TATA box
      and GC box but no upstream CAAT sequence. Alternative splicing results in at
      least two species of mRNA encoding ER-alpha being synthesized from this promoter.
      Transcription profiling of human tissues shows that, among those tested, this
      promoter is predominantly active only in testis and epididymal tissues. Transient
      transfection assays using this new promoter in a number of cell lines indicate
      that the region we have identified functions as a promoter and that tissue
      specific regulation is likely to be dependent on inhibitory sequences greater
      than 1 kb upstream of the transcription start site.

PMID- 12193553
TI  - Survivin as a cell cycle-related and antiapoptotic protein in granulosa cells.
AB  - Survivin is a relatively unique member of the inhibitor of apoptosis protein
      (IAP) family in that it contains a single baculovirus IAP repeat (BIR) domain
      combined with a COOH-terminal alpha-helix coiled-coil domain instead of the more
      common zinc-binding RING finger. Results from a variety of transformed or
      continuous mammalian cell lines suggest that, due to the combination of these
      features, Survivin is capable of regulating both cell proliferation and apoptotic
      cell death. However, to date there is essentially no information regarding
      Survivin expression, regulation or function within the ovary, or in any
      nonmammalian vertebrate species. In the present studies, cDNAs for chicken (ch)
      Survivin-142 (homologous to human Survivin-142) plus three alternatively spliced
      variants (ch Survivin-short, -gamma, and -delta) are described, and of these,
      transcripts for ch Survivin-142 and -short are expressed in granulosa cells from
      the hen ovary. Highest levels of Survivin mRNA during follicle development occur
      in mitotically active granulosa cells from undifferentiated, prehierarchal
      follicles. Cell cycle analysis determined that Survivin mRNA expression is
      elevated specifically during the G2/M phase of mitosis. Significantly, transient
      transfection with ch Survivin-142 in primary cultures of hen granulosa cells
      attenuates taxol- and N-octanoylsphingosine- (C8-ceramide-) induced caspase-3
      activity, whereas overexpression of ch Survivin-short (a truncated variant that
      lacks much of the functional BIR domain plus the entire alpha-helix coil domain)
      lacks this antiapoptotic activity. Taken together, these data provide evidence
      for Survivin in granulosa cells acting as a bifunctional protein associated with
      regulation of the cell cycle and the inhibition of apoptosis.

PMID- 12193555
TI  - Estrogen mediates mammary epithelial cell proliferation in serum-free culture
      indirectly via mammary stroma-derived hepatocyte growth factor.
AB  - Epithelial-stromal cell interactions are important for normal development and
      function of the mouse mammary gland. The steroid hormone estrogen is required for
      epithelial cell proliferation and ductal development in vivo. Recent studies of
      estrogen receptor alpha knockout mice indicate that estrogen-induced
      proliferation is dependent upon the presence of estrogen receptor in mammary
      stromal cells, but not in epithelial cells. The purpose of the present study was
      to identify the underlying mechanism of estrogen-dependent stroma-derived effects
      on mammary epithelium. We have developed a minimally supplemented serum-free
      medium, collagen gel primary mammary coculture system to address the issue of
      stroma-derived, estrogen-dependent effects on epithelial cell proliferation.
      Conditioned medium from mammary fibroblasts or coculture with mammary fibroblasts
      caused increased epithelial cell proliferation and produced tubular/ductal
      morphology. Hepatocyte growth factor (HGF) was identified as the mediator of this
      effect, as the proliferative activity in fibroblast-conditioned medium was
      completely abolished by neutralizing antibody to HGF, whereas neutralizing
      antibodies to either epidermal growth factor or IGF-I had no effect. Treatment of
      mammary fibroblasts with estrogen increased the production of HGF. From these
      results we conclude that estrogen may indirectly mediate mammary epithelial cell
      proliferation via the regulation of HGF in mammary stromal cells and that HGF
      plays a crucial role in estrogen-induced proliferation in vivo.

PMID- 12193554
TI  - Different signaling pathways control acute induction versus long-term repression
      of LHbeta transcription by GnRH.
AB  - GnRH regulates pituitary gonadotropin gene expression through GnRH receptor
      activation of the protein kinase C (PKC) and calcium signaling cascades. The
      pulsatile pattern of GnRH release is crucial for induction of LHbeta-subunit
      (LHbeta) gene expression; however, continuous prolonged GnRH exposure leads to
      repression of LHbeta gene transcription. Although in part, long-term repression
      may be due to receptor down-regulation, the molecular mechanisms of this
      differential regulation of LHbeta transcription are unknown. Using transfection
      into the LH-secreting immortalized mouse gonadotrope cell line (LbetaT4), we have
      demonstrated that LHbeta gene transcription is increased by acute activation (6
      h) of GnRH receptor or PKC but not calcium influx; in contrast long-term
      activation (24 h) of GnRH receptor, PKC, or calcium influx each repress LHbeta
      transcription. Whereas blockade of PKC prevented the acute action of GnRH and
      unmasked an acute repression of LHbeta transcription by calcium, it did not
      prevent long-term repression by GnRH or calcium. Removal of calcium resulted in
      potentiation of acute GnRH and PKC induction of LHbeta gene expression but
      prevented long-term repression by GnRH and reduced long-term repression by either
      calcium or 12-O-tetradecanoyl-phorbol-13-acetate (TPA). We conclude that GnRH
      uses PKC for acute induction, and calcium signaling is responsible for long-term
      repression of LHbeta gene expression by GnRH. Furthermore, analysis of the
      responsiveness of truncated and mutated LHbeta promoter regions demonstrated that
      not only do acute induction and long-term repression use different signaling
      systems, but they also use different target sequences for regulating the LHbeta
      gene.

PMID- 12193557
TI  - Low density lipoprotein can cause death of islet beta-cells by its cellular
      uptake and oxidative modification.
AB  - Islet beta-cells express receptors for low density (LDL) and very low density
      (VLDL) lipoproteins that are internalized by receptor-mediated endocytosis. The
      present study examined whether this process can affect the viability of isolated
      rat islet beta-cells. Culture with LDL (from 6 micro g/ml on), but not VLDL,
      causes necrosis of beta-cells within 2 d. No toxicity was observed when LDL
      binding and/or endocytosis was prevented by low temperature (8 C), or by addition
      of heparin or an excess of VLDL. The LDL toxicity did not occur in the presence
      of antioxidants (probucol or a mixture of glutathion, vitamins A, C, E plus
      dithiothreitol) or of the radical scavenger butylated hydroxytoluene. The degree
      of LDL-induced toxicity was correlated with an increase in the electrophoretic
      mobility of LDL, an index for its oxidative modification. Both LDL toxicity and
      oxidation were suppressed by omission or chelation of copper and iron in the
      medium. Addition of oxidized LDL was not cytotoxic to beta-cells, which lack
      oxidized LDL receptors. It is concluded that uptake of LDL by islet beta-cells
      and subsequent oxidative reactions can be damaging for the cells. This process
      can be counteracted by HDL and VLDL, and by antioxidants.

PMID- 12193558
TI  - Chicken ghrelin: purification, cDNA cloning, and biological activity.
AB  - In this study, we report the purification, cDNA cloning, and characterization of
      the novel growth hormone-releasing peptide, ghrelin, in the chicken (Gallus
      gallus). Chicken ghrelin is composed of 26 amino acids
      (GSSFLSPTYKNIQQQKDTRKPTARLH) and possesses 54% sequence identity with human
      ghrelin. The serine residue at position 3 (Ser(3)) is conserved between the
      chicken and mammalian species, as its acylation by either n-octanoic or n
      decanoic acid. Chicken ghrelin mRNA is predominantly expressed in the stomach,
      where it is present in the proventriculus but absent in the gizzard. Using RT-PCR
      analysis, low levels of expression were also detectable in brain, lung, and
      intestine. Administration of chicken ghrelin increases plasma GH levels in both
      rats and chicks, with a potency similar to that of rat or human ghrelin. In
      addition, chicken ghrelin also increases plasma corticosterone levels in growing
      chicks at a lower dose than in mammals. The present results indicate that the
      stimulatory effect of ghrelin on GH secretion is evolutionarily conserved,
      whereas its effect on adrenal function seems to be unique in the chicken.

PMID- 12193556
TI  - A 77-base pair LINE-like sequence elicits androgen-dependent mvdp/akr1-b7
      expression in mouse vas deferens, but is dispensable for adrenal expression in
      rats.
AB  - Mvdp/akr1-b7 (mouse vas deferens protein/aldo-keto reductase 1-B7) encodes an
      enzyme responsible for detoxification of a steroidogenesis byproduct. MVDP/AKR1
      B7 is expressed in both rat and mouse adrenal cortex under ACTH control, whereas
      strong androgen-dependent accumulation in the vas deferens is mouse specific.
      Comparison of the regulatory regions of the two orthologs reveals a strong
      identity, disrupted by acquisition of a 77-bp LINE-derived sequence in the mouse
      promoter. Although ACTH responsiveness is observed in both species, the absence
      of this 77-bp sequence in the rat is associated with changes in transcription
      initiation sites. Transfection studies demonstrate that the CCAAT/enhancer
      binding protein and selective promoter factor 1-binding sites previously shown to
      be essential for cAMP/ACTH induction in the mouse are consequently dispensable in
      the rat. Our data support the idea that the most striking change generated by
      this acquisition is the strong, androgen-dependent, vas deferens expression
      observed in mouse. 1) In rat vas deferens, rakr1-b7 expression is barely
      detectable and is not androgen sensitive. 2) Androgen receptor binds efficiently
      to an androgen response element within the 77-bp mouse-specific element. 3) Its
      insertion confers androgen sensitiveness to rakr1-b7 regulatory regions in an
      androgen response element-dependent manner in transient transfections. We propose
      that this acquired androgen-responsive region may be responsible for vas deferens
      androgen-regulated gene expression in vivo.

PMID- 12193559
TI  - Cellular specificity of proexendin-4 processing in mammalian cells in vitro and
      in vivo.
AB  - Glucagon-like peptide-1 (GLP-1) is a potent stimulator of glucose-dependent
      insulin secretion. Exendin-4(1-39) (Ex-4), isolated from Gila monster venom, is a
      highly specific GLP-1 receptor agonist that exhibits a prolonged duration of
      action in vivo. Although the processing mechanisms underlying liberation of GLP-1
      from its prohormone have been elucidated, those for Ex-4 remain unknown. To
      examine the requirements for proEx-4 processing in mammalian cells, BHK
      fibroblasts, InR1-G9 islet A cells, and AtT-20 corticotropes, which express
      different prohormone convertases (furin, prohormone convertase 2, and prohormone
      convertase 1, respectively) were transfected with full-length lizard proEx-4, and
      the processing of proexendin was examined by HPLC and RIA (n = 3). All of the
      transfected cell lines exhibited Ex-4-like immunoreactivity in the media, and Ex
      4-like immunoreactivity was detected in extracts of InR1-G9 and AtT-20 cells.
      However, only media and extracts from AtT-20 cells (not InR1-G9 and BHK cells)
      contained a single peak by HPLC corresponding to synthetic Ex-4. To establish
      whether proEx-4 can be processed to Ex-4 in nonimmortalized mammalian cells in
      vivo, the molecular forms of exendin-4 were examined in mice expressing a
      metallothionein-proEx-4 transgene (n = 3-6 for both males and females). ProEx4
      mRNA transcripts were detected by RT-PCR in a broad range of both endocrine and
      nonendocrine tissues. Ex-4-like immunoreactivity was detected in pituitary, fat,
      adrenals, and testes; however HPLC analyses demonstrated that processed Ex-4 was
      found only in adrenals and testes. These results indicate that lizard proEx-4 is
      processed to mature bioactive Ex-4 in both rodent endocrine and nonendocrine
      mammalian cell types in vitro and in murine tissues in vivo. These findings may
      be useful for engineering cells that express a lizard pro-Ex4 transgene for the
      treatment of type 2 diabetes.

PMID- 12193560
TI  - Expression and processing of the [Pro(2),Met(13)]somatostatin-14 precursor in the
      intermediate lobe of the frog pituitary.
AB  - The biosynthesis of various hypothalamic neuropeptides has been previously
      reported in anterior pituitary cells but not in intermediate lobe cells. We have
      recently demonstrated the occurrence of two somatostatin isoforms in the frog
      brain, namely somatostatin-14 (SS1) and [Pro(2),Met(13)]somatostatin-14 (SS2). In
      the present study, we demonstrate that the gene encoding the SS2 precursor (PSS2)
      is actively expressed in the intermediate lobe of the frog pituitary. High
      concentrations of PSS2 mRNA have been detected by Northern blot analysis and in
      situ hybridization in the frog pars intermedia but not in the pars distalis or
      pars nervosa. The distribution of PSS1- and PSS2-derived peptides has been
      investigated by immunohistochemistry using two antisera directed against SS1 and
      the sequence 54-66 of PSS2 (PSS2(54-66)), respectively. The SS1 antiserum stained
      only a network of fibers in the neural lobe and a few nerve processes in the
      intermediate lobe. In contrast, the PSS2(54-66) antiserum produced intense
      labeling of melanotrope cells in the pars intermedia. Biochemical
      characterization of the immunoreactive materials present in pituitary extracts
      was performed by combining high-performance liquid chromatography analysis and
      RIA detection. The SS1 RIA revealed the existence of two major immunoreactive
      peaks that exhibited the same retention times as synthetic SS1 and SS2. The
      PSS2(54-66) RIA detected a single peak that likely corresponds to the N-flanking
      peptide of SS2 (PSS2(1-66)). The present study reveals that melanotrope cells of
      the frog pituitary selectively express the PSS2 gene and fully process PSS2 to
      generate the mature somatostatin variant SS2. Taken together, these data provide
      the first evidence that the gene encoding a hypophysiotropic neuropeptide is
      intensely expressed in the intermediate lobe of the pituitary.

PMID- 12193561
TI  - Potentiation of glucocorticoid receptor transcriptional activity by sumoylation.
AB  - The glucocorticoid receptor (GR) is a transcription factor, subject to several
      types of posttranslational modifications including phosphorylation and
      ubiquitination. We showed that the GR is covalently modified by the small
      ubiquitin-related modifier-1 (SUMO-1) peptide in mammalian cells. We demonstrated
      that GR sumoylation is not dependent on the presence of the ligand and regulates
      the stability of the protein as well as its transcriptional activity. SUMO-1
      overexpression induces dramatic GR degradation, abolished by proteasome
      inhibition. We also found that SUMO-1 stimulates the transactivation capacity of
      GRs to an extent largely exceeding those observed so far for other sumoylated
      transcription factors. Overexpression of SUMO-1 specifically enhances the ligand
      induced transactivation of GR up to 8-fold. However, this hyperactivation occurs
      only in the context of a synergy between multiple molecules of GRs. It requires
      more than one receptor DNA-binding site in promoter and becomes more prominent as
      the number of sites increases. Interestingly, these observations may be related
      to the transcriptional properties of the synergy control region of GRs, which
      precisely contains two evolutionary conserved sumoylation sites. We propose a
      model in which SUMO-1 regulates the synergy control function of GR and serves as
      a unique signal for activation and destruction.

PMID- 12193562
TI  - Polyethylene glycolated recombinant TNF receptor I improves insulitis and reduces
      incidence of spontaneous and cyclophosphamide-accelerated diabetes in nonobese
      diabetic mice.
AB  - We have conducted three studies to examine the role of TNFalpha in islet
      destruction in female nonobese diabetic mouse (NOD) mice, a model of human
      autoimmune diabetes, using polyethylene glycolated (PEGylated) soluble TNF
      receptor type I (PEG sTNF-RI) as TNFalpha antagonist. PEG sTNF-RI (3 mg/kg, sc)
      was given every other day to NOD mice from age wk 8 for 12 wk (study 1), from age
      wk 12 for 8 wk (study 2), or from age wk 8 for 3 wk, with cyclophosphamide (6
      mg/mouse) injected at wk 9 to accelerate the onset of diabetes (study 3).
      Diabetic incidence was reduced (control vs. PEG sTNF-RI) from 68.7% (11 of 16) to
      18.3% (3 of 16) in study 1, from 84.6% (11 of 13) to 28.5% (4 of 14) in study 2,
      and from 66.6% (8 of 12) to 23.1% (3 of 13) in study 3, respectively. The
      incidence of insulitis was also reduced from 91.6% (11 of 12) to 12.5% (2 of 16)
      in study 1 and from 100% (7 of 7) to 16.6% (2 of 12) in study 2 by PEG sTNF-RI.
      PEG sTNF-RI also largely preserved islet insulin content, reduced mRNA of
      inducible nitric oxide synthase and IL-6 in pancreases, and lowered plasma
      corticosterone, glycerol, and free fatty acid levels. These results confirm a
      pathogenic role of TNFalpha in mediating insulitis in NOD mice and suggest the
      prophylactic and therapeutic potential of PEG sTNF-RI for human autoimmune
      diabetes.

PMID- 12193563
TI  - Brain stem is a direct target for leptin's action in the central nervous system.
AB  - Leptin is a circulating molecule for the regulation of food intake and body
      weight suggested to be mediated in the hypothalamus via Ob-Rb receptor, which
      activates Janus kinase-signal transducer and activator of transcription (STAT)
      pathways. Although leptin receptors exist in many regions of the brain, there
      have been few in vivo functional studies of leptin's target site other than the
      hypothalamus. We report here that peripherally applied leptin increased STAT3
      phosphorylation not only in the hypothalamus but also in the brain stem as
      assessed by Western blotting. Moreover, administration of leptin induced
      expression of the suppressor of cytokine signaling 3 mRNA, a negative feedback
      regulator of leptin signaling, in the brain stem as well as in the hypothalamus.
      Using immunohistochemistry, we observed phosphorylated STAT3-immunoreactive cells
      in the arcuate nucleus, ventromedial hypothalamus, lateral hypothalamic area of
      the hypothalamus, and the nucleus of the tractus solitarius, dorsal motor nucleus
      of the vagus nerve, lateral parabrachial nucleus, and central gray of the brain
      stem of leptin-injected mice. These findings represent physiologically functional
      leptin Ob-Rb receptor in the brain stem as well as in the hypothalamus. It is
      suggested that circulating leptin may directly act in the brain stem to elicit
      autonomic and neuroendocrine control of food intake and energy expenditure.

PMID- 12193564
TI  - Functional maturation of fetal porcine beta-cells by glucagon-like peptide 1 and
      cholecystokinin.
AB  - Fetal beta-cells are immature in their responsiveness to glucose, and maturation
      occurs after oral feeding commences at birth. The incretin hormones glucagon-like
      peptide 1 (GLP-1) and cholecystokinin (CCK) are known to be released from the gut
      in response to oral feeding and enhance insulin secretion from pancreatic beta
      cells. We hypothesized that these fetal beta-cells would mature in their glucose
      responsiveness if they were previously exposed to incretins. We exposed fetal pig
      islet-like cell clusters (ICCs) to 100 nM GLP-1, 5 micro M CCK, or 10 mM
      nicotinamide (NIC; a positive control) for 6 h and demonstrated 3- and 1.7-fold
      increases in glucose-induced insulin secretion for GLP-1 and CCK, respectively.
      This effect did not reach statistical significance if the ICCs were exposed to
      the incretins for 3 d. However, exposure for 4 d enhanced formation of beta-cells
      from undifferentiated cells, from 8 +/- 1% (controls) to 17 +/- 3% for GLP-1, 20
      +/- 4% for CCK, and 15 +/- 1 for NIC (P < 0.001). ICCs exposed to GLP-1 for 3 d
      also showed a 1.9-fold increase in the intensity of PDX-1(+) cells, as assessed
      by semiquantitative fluorescent immunocytochemistry. Exposure of ICCs to
      incretins for 3 d did not show any increase in size of the islet clusters. ICCs
      exposed to either incretin as well as controls were transplanted into severe
      combined immunodeficient mice and examined at 1 and 2 months. We found a
      significant increase in the number of beta-cells in the GLP-1- and NIC-treated
      groups compared with the untreated controls or CCK. Perfusion of these grafts at
      2 months showed that ICCs previously exposed to GLP-1, CCK, and NIC (but not
      controls), were functional and mature. In conclusion, GLP-1 and CCK have a dual
      effect on fetal pig ICCs, causing maturation of glucose-induced insulin secretion
      from beta-cells as well as enhancement of differentiation from undifferentiated
      precursors.

PMID- 12193565
TI  - Adrenomedullin inhibits doxorubicin-induced cultured rat cardiac myocyte
      apoptosis via a cAMP-dependent mechanism.
AB  - We previously reported that adrenomedullin produced by cardiac myocytes acts as a
      local modulator in some cardiac disorders. However, the role of adrenomedullin
      (AM) in cardiomyocyte apoptosis remains to be clarified. The present study
      investigated the effect of AM on doxorubicin-induced cardiac myocyte apoptosis.
      Doxorubicin increased the number of cells with pyknotic nuclei and lactate
      dehydrogenase release, and AM dose-dependently (10(-10)-10(-8)6 M) inhibited
      these increases produced by doxorubicin. Treatment with AM also suppressed
      doxorubicin-induced DNA fragmentation and caspase-3 activation. 8-Bromo-cAMP, a
      cAMP analog, mimicked these antiapoptotic effects of AM. An AM/calcitonin gene
      related peptide (CGRP) receptor antagonist CGRP-(8-37) and a protein kinase A
      inhibitor H89 attenuated the antiapoptotic effect of AM. CGRP-(8-37) and H89 had
      no apoptotic effect alone, but accelerated doxorubicin-induced apoptosis. Under
      serum-free conditions, AM secretion into the culture medium and expression of AM
      mRNA were significantly increased after treatment with doxorubicin. Hydrogen
      peroxide scavenger catalase and antioxidant N-acetyl-L-cysteine inhibited the
      doxorubicin-mediated increase in AM secretion and its gene expression. These
      results indicate that AM inhibits doxorubicin-induced cardiac myocyte apoptosis
      through a cAMP-dependent mechanism and suggest that augmented production of AM by
      doxorubicin has an endogenous antiapoptotic effect. AM, as an autocrine factor,
      may play a protective role against cardiomyocyte injury by doxorubicin.

PMID- 12193566
TI  - Antiangiogenic and antitumor effects of endostatin on follicular thyroid
      carcinoma.
AB  - Tumor growth and metastasis depend on blood supply and blood vessel formation.
      Angiogenesis, therefore, represents a promising target for cancer therapy.
      Endostatin is one of the most potent antiangiogenic factors and has been shown to
      effectively inhibit angiogenesis and tumor growth in a variety of in vivo models.
      In this study, we tested the effects of endostatin on xenografted human
      follicular thyroid carcinoma (FTC) in nude mice. Our result demonstrated that
      recombinant endostatin significantly inhibited the growth of FTC xenografts.
      Furthermore, we established an endostatin-expressing FTC cell line (FTC-BmEndo)
      using retrovirus-mediated gene transfer approach. We found that the in vivo
      growth of FTC-BmEndo cells was significantly inhibited, compared with the
      parental FTC cells, whereas both lines grew at the same rate in vitro. High-level
      expression of endostatin within the FTC-BmEndo tumors was evidenced by
      immunohistochemical staining, paralleled with a reduced microvessel density. The
      systemic level of vascular endothelial growth factor was significantly lower in
      mice bearing the FTC-BmEndo tumors than in those bearing parental FTC tumors. By
      using two different approaches, namely the recombinant endostatin protein and the
      gene therapy strategy, our study demonstrated that endostatin could be effective
      in suppressing the growth of human FTC in immunodeficient mice.

PMID- 12193567
TI  - Transfection of pancreatic-derived beta-cells with a minigene encoding for human
      glucagon-like peptide-1 regulates glucose-dependent insulin synthesis and
      secretion.
AB  - Glucagon-like peptide-1 (GLP-1) is an incretin hormone derived from the
      proglucagon gene, capable of regulating the transcription of the three major
      genes that determine the pancreatic beta-cell-specific phenotype: insulin, GLUT
      2, and glucokinase. The aim of this study was to investigate the potential role
      of GLP-1 for the gene therapy of glucose-insensitive pancreatic beta-cells. We
      transfected mouse insulinoma cells with a DNA fragment of the human proglucagon
      gene containing the nucleotide sequence encoding for human GLP-1 but lacking the
      coding region for glucagon. Two constructs were generated: In one, the expression
      of GLP-1 was under the control of the cytomegalovirus (CMV) promoter (CMV/GLP-1),
      and the second was regulated by the rat insulin II promoter (RIP)/GLP-1).
      Northern blot, HPLC, and RIA analyses confirmed that the minigene was transcribed
      and the protein appropriately translated, processed, and secreted in the
      extracellular environment. Gene expression studies revealed that although CMV/GLP
      1 cells did not gain a greater glucose sensitivity as a result of the
      transfection with GLP-1, compared with cells transfected with the plasmid alone,
      RIP/GLP-1 was capable of regulating the gene expression of insulin and GLP-1
      based on the concentration of glucose in the culture medium. Detection of the
      counterpart proteins (insulin and GLP-1) in the culture medium paralleled the
      observation derived from the Northern blot analysis. GLP-1 action was mediated by
      an IDX-1 (islet/duodenum homeobox-1) dependent transactivation of the endogenous
      insulin promoter, as demonstrated by gel shift analysis. This was further
      suggested by a significant increase of the glucose-dependent binding of IDX-1 to
      the insulin promoter in RIP/GLP-1 cells but not in CMV/GLP-1 cells or control
      cells. Finally, we observed that although the GLP-1-dependent secretion of
      insulin was mediated by an increase in cAMP levels, the transcription of the
      insulin gene, in response to GLP-1, was in large part cAMP independent. The
      present study lays the research foundation to investigate the potential use of
      GLP-1 for the gene or cell therapy of diabetes.

PMID- 12193568
TI  - Up-regulation of the expression of activins in the pancreatic duct by reduction
      of the beta-cell mass.
AB  - Activins expressed in progenitor cells of the pancreas regulate differentiation
      of endocrine cells during development. Neogenesis of beta-cells takes place in
      adult animals under some conditions, and beta-cells are thought to arise from
      precursors locating in the pancreatic duct. In the present study, we investigated
      whether or not activins are expressed in the duct where beta-cell neogenesis is
      initiated. mRNA for the beta(A)- and beta(B)-subunits was expressed in isolated
      mouse pancreatic ducts. Immunohistochemically, the beta(A)-subunit was detected
      in the pancreatic duct and colocalized with cytokeratin, a marker of ductal
      cells. The beta(A)-subunit was also expressed in nestin-positive cells in the
      duct. Likewise, the beta(B)-subunit was detected in the pancreatic duct. In
      addition, mRNA for the type II and type IIB activin receptors was expressed in
      the duct. Expression of mRNA for two activin subunits was markedly increased
      after streptozotocin injection. Similarly, the mRNA expression was up-regulated
      after partial pancreatectomy. These results indicate that activins are expressed
      in the pancreatic duct and are up-regulated shortly after the reduction of the
      beta-cell mass. Induction of activins in the duct may be a critical step in the
      initiation of beta-cell neogenesis.

PMID- 12193569
TI  - Calcium dynamics and resting transcriptional activity regulates prolactin gene
      expression.
AB  - Research on the regulation of hormone gene expression by calcium signaling is
      hampered by the difficulty of monitoring both parameters within the same
      individual, living cells. Here we achieved concurrent, dynamic measurements of
      both intracellular Ca(2+) concentration ([Ca(2+)](i)) and prolactin (PRL) gene
      promoter activity in single, living pituitary cells. Cells were transfected with
      the luciferase reporter gene under control of the PRL promoter and subjected to
      bioluminescence and fluorescence imaging before and after presentation of TSH
      releasing hormone (TRH), a prototypic regulator of PRL secretion and gene
      expression that induces a transient Ca(2+) release, followed by sustained Ca(2+)
      influx. We found that cells displaying specific photonic emissions (i.e.
      mammotropes) showed heterogeneous calcium and transcriptional responses to TRH.
      Transcriptionally responsive cells always exhibited a TRH-induced [Ca(2+)](i)
      increase. In addition, transcriptional responses were related to the rate of
      Ca(2+) entry but not Ca(2+) release. Finally, cells lacking transcriptional
      responses (but showing [Ca(2+)](i) rises) exhibited larger levels of resting PRL
      promoter activity than transcriptionally responsive cells. Thus, our results
      suggest that the sustained entry of Ca(2+) induced by TRH (but not the Ca(2+)
      release) regulates transcriptional responsiveness. Superimposed on this
      regulation, the previous, resting PRL promoter activity also controls
      transcriptional responses.

PMID- 12193570
TI  - Leptin inhibits angiotensin II-induced intracellular calcium increase and
      vasoconstriction in the rat aorta.
AB  - Besides its role in body weight control leptin may also act as a vasoactive
      hormone. This study was designed to investigate whether leptin modifies
      angiotensin II (ANG II)-induced vascular responses. The expression of functional
      leptin receptors (OB-Rb) was detected in vascular smooth muscle cells (VSMCs)
      from adult Wistar rats by RT-PCR. Immunocytochemistry and Western blot analysis
      further showed the expression of OB-R protein in VSMCs. The ANG II (10(-7)
      mol/liter)-induced increase in intracellular Ca(2+) was blocked (P < 0.01) by
      leptin (10(-8) mol/liter). Moreover, in calcium-free buffer leptin was able to
      inhibit 65% of the ANG II-induced calcium release from intracellular stores. In
      endothelium-denuded aortic rings from adult Wistar rats no effect of leptin on
      basal tension was observed. However, the ANG II-induced isometric contraction was
      reduced (P < 0.05) by leptin (10(-8) mol/liter). The experiments were also
      performed in age- and sex-matched Zucker rats, in which no effect of leptin on
      ANG II-induced calcium increase and vasoconstriction was observed. It is
      concluded that leptin blocks the vasoconstrictor action of ANG II and inhibits
      the ANG II-induced increase in intracellular Ca(2+) in VSMCs through OB-Rb. These
      findings provide new insight into the physiological effects of leptin on blood
      pressure regulation.

PMID- 12193572
TI  - N-Methyl-D-aspartate receptor subunit expression in GnRH neurons changes during
      reproductive senescence in the female rat.
AB  - During reproductive senescence in females, the function of GnRH neurons becomes
      compromised, and this may play a role in the transition from normal estrous
      cycles to acyclicity. One hypothalamic component of this dysregulation is an
      alteration in the stimulatory effects of glutamate, acting via N-methyl-D
      aspartate receptors (NMDARs), on GnRH release. The present study examined whether
      GnRH neurons express the subunits necessary to make functional NMDARs, and how
      subunit expression may change during aging in association with compromised
      reproductive physiology. Colocalization of the three NMDAR subunits that are most
      abundant in the hypothalamus (NR1, NR2A, or NR2B) with GnRH perikarya was
      determined in female rats at different stages of the reproductive life cycle:
      young (3-4 months) rats with regular estrous cycles, middle-aged (8-10 months)
      rats with regular estrous cycles, middle-aged rats with irregular estrous cycles,
      and middle-aged acyclic rats in persistent estrus. The number, percent, and
      localization of GnRH perikarya expressing NR1, NR2A, or NR2B were mapped and
      quantified by double label immunofluorescence microscopy. Overall, each of the
      NMDAR subunits was present in a majority of GnRH neurons. There were no age- or
      reproductive status-related changes in coexpression of NR1 or NR2A subunits in
      GnRH neurons. However, coexpression of the NR2B subunit, which affects several
      functional channel characteristics, was significantly lower in young compared
      with middle-aged rats, irrespective of reproductive status. This may result in an
      age-related increase in the ratio of the NR2B to the NR1 and NR2A subunits on
      GnRH neurons. These data indicate that the majority of GnRH neurons express the
      proteins needed to receive direct NMDAR-mediated glutamatergic input, and that a
      change in the stoichiometry of the NMDAR pentamer occurs during aging that
      precedes, and may have consequences for, altered neuroendocrine function.

PMID- 12193573
TI  - 3-Methylcholanthrene, which binds to the arylhydrocarbon receptor, inhibits
      proliferation and differentiation of osteoblasts in vitro and ossification in
      vivo.
AB  - 3-Methylcholanthrene (3MC) is a ligand for arylhydrocarbon receptor (AhR), which
      binds dioxin. We examined the effects of 3MC on the proliferation and
      differentiation of osteoblasts using cultures of rat calvarial osteoblast-like
      cells (ROB cells) and mouse calvarial clonal preosteoblastic cells (MC3T3-E1
      cells). Analysis by RT-PCR revealed that the mRNAs for AhR and AhR nuclear
      translocators were expressed in both ROB and MC3T3-E1 cells. Cell proliferation
      and the synthesis of DNA by ROB cells and MC3T3-E1 cells were markedly inhibited
      on exposure of cells to 3MC. Furthermore, 3MC reduced the activity of alkaline
      phosphatase and the rate of deposition of calcium by cells. The level of
      expression of mRNA for osteocalcin, which is a marker of osteoblastic
      differentiation, was also depressed by 3MC. Moreover, when 3MC (1 mg/kg body
      weight) was administered sc to pregnant mice at 10.5, 12.5, and 14.5 d post
      coitus, fetuses examined subsequently at 15.5 or 17.5 d post coitus revealed
      evidence of inhibition of appropriate calcification of bones. The treated
      metacarpals showed no subperiosteal bone matrix histologically. Our findings
      indicate that 3MC might have critical effects on the formation of bone both in
      vivo and in vitro.

PMID- 12193574
TI  - Secretion of monocyte chemoattractant protein-1 by endothelial cells of the
      bovine corpus luteum: regulation by cytokines but not prostaglandin F2alpha.
AB  - Information regarding the regulation of monocyte chemoattractant protein-1 (MCP
      1) in regression of the corpus luteum (CL) is limited. This study tested the
      hypothesis that endothelial cells derived from bovine CL are a source of MCP-1,
      and that proinflammatory cytokines, prostaglandin F2alpha (PGF2alpha), and
      progesterone regulate MCP-1 expression. Endothelial cells were treated without
      (Control) or with PGF2alpha (1 micro M), TNFalpha (100 ng/ml), interferon-gamma
      (IFNgamma, 200 IU/ml), and TNFalpha + IFNgamma for 24 and 48 h in the absence or
      presence of progesterone (P4, 250 ng/ml). Increases in MCP-1 mRNA and protein
      were observed in response to TNFalpha within 24 and 48 h of culture, respectively
      (P < 0.05). Interferon-gamma stimulated (P < 0.05) both MCP-1 mRNA and protein
      after 24 h of culture, and this effect was also sustained through 48 h of culture
      (P < 0.05). Cotreatment of cultures with TNFalpha + IFNgamma lead to further
      increases (P < 0.05) in MCP-1 in both 24- and 48-h cultures. Surprisingly,
      neither PGF2alpha nor P4 affected MCP-1 production. Subsequent experiments
      revealed that the endothelial cells lacked prostaglandin F2alpha receptor mRNA,
      and the MAPK pathway, although present and responsive to growth factor
      stimulation, was unresponsive to PGF2alpha stimulation. In summary, endothelial
      cells derived from bovine CL respond to TNFalpha and IFNgamma stimulation with an
      increase in MCP-1 secretion. In contrast, neither PGF2alpha nor P4 directly
      influenced endothelial expression of MCP-1. These results suggest that cytokines
      stimulate the synthesis of MCP-1 observed during PGF2alpha-induced luteal
      regression.

PMID- 12193571
TI  - Nonhereditary enhancement of progeny growth.
AB  - The im electroporated injection of a protease-resistant GH-releasing hormone cDNA
      into rat dams at 16 d gestation resulted in enhanced long-term growth of the F(1)
      offspring. The offspring were significantly heavier by 2 wk of age, and the
      difference was sustained to 10 wk of age. Consistent with their augmented growth,
      the plasma IGF-I concentration of the F(1) progeny was increased significantly.
      The pituitary gland of the offspring was significantly heavier and contained an
      increased number of somatotrophs and PRL-secreting cells, which is indicative of
      modification of cell lineage differentiation. These unique findings demonstrate
      that enhanced GH-releasing hormone expression in pregnant dams can result in
      intergenerational growth promotion by altering development of the pituitary gland
      in the offspring.

PMID- 12193575
TI  - c-Cbl is a negative regulator of GH-stimulated STAT5-mediated transcription.
AB  - We have previously demonstrated that cellular stimulation with GH results in the
      formation of a multiprotein signaling complex. One component of this multiprotein
      signaling complex is the adapter molecule c-Cbl. Here we have examined the role
      of c-Cbl in the mechanism of GH signal transduction. Forced expression of c-Cbl
      in NIH3T3 cells did not alter GH-stimulated Janus kinase 2 tyrosine
      phosphorylation nor GH-stimulated p44/42 MAPK activation and consequent Elk-1-
      mediated transcription. c-Cbl overexpression did, however, result in enhanced and
      prolonged GH-stimulated activation of phosphatidylinositol 3-kinase. Forced
      expression of c-Cbl did not affect GH-stimulated STAT5 tyrosine phosphorylation,
      nuclear translocation, nor binding to DNA but markedly abrogated GH-stimulated
      STAT5-mediated transactivation. c-Cbl overexpression resulted in increased
      ubiquitination and proteosomal degradation of STAT5 and increased degradation of
      GH-stimulated tyrosine phosphorylated STAT5. Cellular pretreatment with the
      proteosomal inhibitor MG132 reversed the effect of c-Cbl overexpression with
      prolonged duration of GH-stimulated STAT5 tyrosine phosphorylation and
      restoration of STAT5-mediated transcription. Thus, c-Cbl is a negative regulator
      of GH-stimulated STAT5-mediated transcription by direction of STAT5 for
      proteosomal degradation.

PMID- 12193576
TI  - Cyclic GMP-dependent protein kinase II plays a critical role in C-type
      natriuretic peptide-mediated endochondral ossification.
AB  - Longitudinal bone growth is determined by endochondral ossification at the growth
      plate, which is located at both ends of long bones and vertebrae, and involves
      many systemic hormones and local regulators. C-type natriuretic peptide (CNP), a
      third member of the natriuretic peptide family, occurs at the growth plate and
      acts locally as a positive regulator of endochondral ossification through the
      intracellular accumulation of cyclic GMP (cGMP). The increase in cGMP
      concentrations is known to activate different signaling mediators, such as cyclic
      nucleotide phosphodiesterases, cGMP-regulated ion channels, and cGMP-dependent
      protein kinases (cGKs). The type II cGK (cGKII)-deficient mice (Prkg2(-/-) mice)
      develop dwarfism as a result of impaired endochondral ossification, suggesting
      that cGKII is important for the CNP-mediated endochondral ossification. However,
      given that Prkg2(-/-) mice differ from CNP-deficient mice (Nppc(-/-) mice) in the
      growth plate histology, which downstream mediator(s) of cGMP play key roles in
      the process is still an enigma. Here we show that targeted expression of CNP in
      the growth plate chondrocytes fails to rescue the skeletal defect of Prkg2(-/-)
      mice. Using cultured fetal mouse tibias, an in vitro model system of endochondral
      ossification, we also demonstrated that CNP cannot increase the longitudinal bone
      growth, and chondrocytic proliferation and hypertrophy, and cartilage matrix
      synthesis in Prkg2(-/-) mice. This study provides in vivo and in vitro genetic
      evidence that cGKII plays a critical role in CNP-mediated endochondral
      ossification.

PMID- 12193577
TI  - TNF-alpha induces apoptosis of lactotropes from female rats.
AB  - TNF-alpha is involved in the regulation of normal tissue homeostasis affecting
      cell proliferation, differentiation, and death. We previously reported that TNF
      alpha reduces anterior pituitary cell proliferation and PRL release in an
      estrogen-dependent manner. In the present project we studied the induction of
      apoptosis by TNF-alpha in anterior pituitary cells from female rats. TNF-alpha
      (50 ng/ml) decreased the viability of anterior pituitary cells. Incubation with
      TNF-alpha for 24 h increased the percentage of terminal
      deoxynucleotidyltransferase-mediated deoxyuridine triphosphate nick end labeling
      positive cells. TNF-alpha increased the percentage of somatotropes and
      lactotropes with apoptotic nuclear morphology without affecting the proportion of
      apoptotic corticotropes or gonadotropes. TNF-alpha increased the percentage of
      apoptotic lactotropes in cultured cells from rats killed in proestrus and estrus,
      but not in diestrus. This effect was significantly higher in cells from rats in
      proestrus than in estrus. In anterior pituitary cells from ovariectomized rats,
      TNF-alpha significantly increased the percentage of apoptotic lactotropes only
      when the cells were incubated in the presence of 17beta-estradiol. These results
      indicate that TNF-alpha induces apoptosis in somatotropes and lactotropes from
      female rats. The apoptotic effect of TNF-alpha on lactotropes is dependent on
      estrogens and could be involved in the regulation of anterior pituitary cell
      renewal during the estrous cycle.

PMID- 12193578
TI  - Emergence of uterine pathology during accelerated biological aging in FSH
      receptor-haploinsufficient mice.
AB  - A fully functional FSH receptor (Fshr) is required for ovarian follicular
      development and fertility. Fshr null females are sterile because of failure of
      follicular maturation, ovulation, and estrogen deficiency. Because Fshr
      haploinsufficient females also begin to show age-dependent reproductive deficits
      that mimic biological aging, we have investigated the changes that occur in the
      uterus of these mice. The uterine weight in 12-month-old Fshr +/- mice increased
      2-fold, and most retired breeders (those that stopped breeding earlier than our
      wild-type females) developed unilateral uterine masses that appeared similar to
      several abnormalities that also occur in women and associated with infertility.
      Curiously, there was a tendency for most of the abnormality to occur in the right
      horn. Up to 25% of the virgin Fshr-haploinsufficient mice also developed
      pathology. These transformations were not present in either wild-type mice or the
      estrogen-deficient Fshr null females at any age. In haploinsufficient females,
      estrogen and progesterone were reduced and testosterone was elevated in
      circulation by 1 yr. Fshr-haploinsufficient mice developed an imbalance of
      progesterone receptor isoforms A and B in the uterus. This alteration of
      progesterone receptors along with an increase in LH receptors in the uterus may
      contribute to the induction of high frequency of uterine pathology. Angiogenesis,
      vascular abnormality, and adenomyosis appeared to be increased in the uterine
      horn bearing pathological mass. The Fshr-haploinsufficient mice might help in
      understanding the molecular basis of induction of uterine pathology and tissue
      patterning.

PMID- 12193579
TI  - Retinoic acid receptors and retinoids are up-regulated in the developing and
      adult rat prostate by neonatal estrogen exposure.
AB  - Exposure to estrogens during the neonatal period interrupts rat prostatic
      development by reducing branching morphogenesis and by blocking epithelial cells
      from entering a normal differentiation pathway. Upon aging, ventral prostates
      exhibit extensive hyperplasia, dysplasia, and massive lymphocytic infiltrate,
      suggesting that neonatal estrogens may predispose the prostate gland to
      precancerous lesions. Vitamin A (retinol) and their derivatives (retinoic acids)
      are known key developmental regulators that bind and activate retinoic acid
      receptors (RARs). To evaluate whether neonatal estrogenization alters the
      sensitivity of the developing rat prostate to retinoids, RARalpha, -beta, and 
      gamma cellular localization and protein levels were analyzed over the course of
      development and into adulthood by immunocytochemistry and Western analysis,
      whereas mRNA levels were measured using RT-PCR. In addition, intraprostatic
      retinol and retinoic acid levels were quantitated on d 10 and 90 using HPLC-mass
      spectroscopy. Male rats were given 25 micro g estradiol benzoate or oil on d 1,
      3, and 5 of life, and prostatic complexes were removed on d 6, 10, 15, 30, and
      90. The RARs localized to distinct cell populations: RARbeta was expressed within
      basal epithelial cells, RARalpha was localized to differentiated luminal
      epithelial cells and smooth muscle cells, and RARgamma was expressed within
      periductal stromal cells. Over the normal course of development, total protein
      and mRNA levels for the RARs declined, so that the adult prostate possessed the
      lowest amounts of RAR. Exposure to estrogens during the neonatal period resulted
      in an immediate and sustained increase in RARalpha levels and in the number of
      cells that expressed RARbeta, whereas RARgamma levels were unaffected. Western
      analysis confirmed that total prostatic RAR protein levels were significantly
      increased, whereas RT-PCR demonstrated that RARalpha and RARbeta mRNA levels were
      markedly elevated in response to estrogenic exposure. The total prostatic retinol
      content was tripled by estrogenic exposure on d 10 and 90, indicating that the
      ability to retain retinoids within the prostate was permanently increased.
      Intraprostatic levels of 9-cis- and all-trans-retinoic acid levels were reduced
      on d 10, whereas 13-cis-retinoic acid levels were increased in response to
      estrogens. In the adult prostates of rats exposed neonatally to estrogen, total
      retinoic acid levels were doubled due to significant increases in both 9-cis- and
      13-cis-retinoic acids compared with those in control prostates. In summary,
      levels of specific RARs and their activating ligands are increased in the
      prostate gland after neonatal estrogenic exposure, and this effect is permanent
      throughout the life of the animal. Thus, we hypothesize that alterations in
      morphogenesis as well as dysplasia in the adult prostate may be mediated in part
      through augmentation of transcriptional signals in the retinoid pathway.

PMID- 12193580
TI  - Deletion of Stat3 blocks mammary gland involution and extends functional
      competence of the secretory epithelium in the absence of lactogenic stimuli.
AB  - The transcription factor Stat3 is activated through tyrosine phosphorylation by
      many cytokines and is a fundamental mediator of their signals. In the mammary
      gland, Stat3 activity increases sharply shortly after weaning, and involution is
      delayed in mice, that contain a mutant Stat3 lacking 33 amino acids including the
      key tyrosine residue. We have now generated a more extensive mutation of Stat3
      through the deletion of exons 15-21 in mammary epithelium. This resulted in the
      loss of 245 amino acids including the DNA binding and SH2 domains, and Stat3
      protein was undetectable. Pregnancy-mediated mammary development and lactation
      were normal in these mice. Involution was delayed and, remarkably, Stat3-null
      mammary epithelium maintained its functional integrity and competence even 6 d
      after weaning, whereas control mammary tissue was rendered nonfunctional within 2
      d. The lack of remodeling and functional stasis of the epithelium correlated with
      the disruption of proteinase activity. Our data demonstrate that mammary tissue
      can retain its functional competence in the absence of external lactogenic
      stimuli and demonstrate a delay in the initiation of the irreversible stage of
      involution.

PMID- 12193581
TI  - Calmodulin-dependent kinase I regulates adrenal cell expression of aldosterone
      synthase.
AB  - Aldosterone synthase (CYP11B2) is expressed in the adrenal glomerulosa and
      controls the capacity of the adrenal glomerulosa to produce aldosterone. Herein,
      human NCI-H295R (H295R) adrenocortical cells were used to define the calcium
      dependent mechanisms regulating CYP11B2 gene transcription using reporter
      constructs containing CYP11B2 gene 5'-flanking DNA. Treatment of H295R cells with
      calcium/calmodulin-dependent protein kinase (CaMK) inhibitor (KN93) or calmodulin
      inhibitor (calmidazolium) blocked angiotensin II and potassium (K(+)) stimulation
      of CYP11B2 reporter gene expression. To determine which CaMK regulates CYP11B2,
      vectors containing the complete coding sequences for CaMKI, CaMKII, and CaMKIV
      were transfected with the CYP11B2 reporter construct. CaMKI augmented reporter
      expression when cellular calcium was elevated by ionomycin, whereas CaMKIV had a
      small effect, and CaMKII had no effect. To further study the role of CaMKs,
      constitutively active forms of CaMKI (CaMKI-295), II (CaMKII-290), and IV (CaMKIV
      313) were transfected with CYP11B2 reporter constructs. CaMKI-295 and, to a
      lesser degree, CaMKIV-313 were able to stimulated reporter activity. Mutational
      analysis of the 5'-flanking region of CYP11B2 revealed that a cAMP regulatory
      element (-71/-64) was necessary for CaMKI induction of reporter gene activity.
      CaMKI expression was shown in adrenal cortex and H295R cells using
      immunohistochemistry and Western and Northern analyses. These findings suggest
      that CaMKI is involved in angiotensin II and K(+) stimulation of CYP11B2
      transcription and, therefore, the capacity of the adrenal to produce aldosterone.

PMID- 12193582
TI  - Estrogen receptor-related receptor alpha impinges on the estrogen axis in bone:
      potential function in osteoporosis.
AB  - The orphan nuclear estrogen receptor-related receptor alpha (ERRalpha) is
      expressed by osteoblastic cells and plays a functional role in osteoprogenitor
      proliferation and differentiation. To dissect further the role of ERRalpha in
      bone, we investigated the effects of estrogen (E2) on ERRalpha both in vitro and
      in vivo. Chronic treatment of fetal rat calvaria cells with E2-stimulated bone
      nodule formation and up-regulated ERRalpha mRNA expression at early (10 h and d
      8) but not later times in culture, suggesting a link between ERRalpha and E2
      during osteoprogenitor proliferation. ERRalpha mRNA levels were significantly
      lower in ovariectomized adult rat bones vs. those of sham-operated rats early (1
      d and 1 wk) post surgery, but levels returned to control levels thereafter.
      ERRalpha is also expressed in osteoclasts (tartrate-resistant acid phosphatase +
      multinucleated cells) in vivo and in vitro (RAW 264.7 cells) and
      ovariectomization lowered the OPG/receptor activator of nuclear factor kappaB
      ligand expression ratio. Down-regulation of ERRalpha expression via antisense
      treatment of rat calvaria cells not only inhibited osteogenesis but also
      increased adipocyte colony formation and changed the OPG/receptor activator of
      nuclear factor kappaB ligand ratio. These data suggest that ERRalpha is regulated
      by estrogen in bone in which it may play a functional role at several levels
      (osteoblasts, adipocytes, and osteoclasts) in E2 deficiency diseases such as
      osteoporosis.

PMID- 12193583
TI  - Ovarian hyperstimulation by LH leads to mammary gland hyperplasia and cancer
      predisposition in transgenic mice.
AB  - Many risk factors for breast cancer are associated with hormonally regulated
      events. Although numerous mouse models of mammary cancer exist, few address the
      roles of hormones in spontaneous tumor formation. Here we report that transgenic
      mice that overexpress LH, resulting in ovarian hyperstimulation, undergo
      precocious mammary gland development. A significant increase in proliferation
      leads to ovary-dependent mammary gland hyperplasia. Transgenic glands
      morphologically mimic those of wild-type pregnant mice and expression levels of
      multiple milk protein genes are comparable with what is observed at d 14 of
      pregnancy. In addition to sustained hyperplasia, spontaneous mammary tumors were
      observed with a mean latency of 41 wk, indicating that chronic hormonal
      stimulation causes mammary cancer. Although hormonally induced, these tumors lack
      expression of progesterone receptor, suggesting that following initiating events,
      the tumors may become hormone independent. This mouse model likely holds great
      potential as a tool for discovery of hormone-mediated mechanisms of breast cancer
      and identification of future targets for breast cancer prevention and treatment.

PMID- 12193584
TI  - Stanniocalcin 1 alters muscle and bone structure and function in transgenic mice.
AB  - Fish stanniocalcin (STC) inhibits uptake of calcium and stimulates phosphate
      reabsorption. To determine the role of the highly homologous mammalian protein,
      STC-1, we created and characterized transgenic mice that express STC-1 under
      control of a muscle-specific promoter. STC-1 transgenic mice were smaller than
      wild-type littermates and had normal growth plate cartilage morphology but
      increased cartilage matrix synthesis. In STC-1 mice, the rate of bone formation,
      but not bone mineralization, was decreased. Increased cortical bone thickness and
      changes in trabeculae number, density, and thickness in STC-1 mice indicated a
      concomitant suppression of osteoclast activity, which was supported by
      microcomputed tomography analyses and histochemistry. Skeletal muscles were
      disproportionately small and showed altered function and response to injury in
      STC-1 mice. Electron microscopy indicated that muscle mitochondria were
      dramatically enlarged in STC-1 mice. These changes in STC-1 mice could not be
      explained by deficits in blood vessel formation, as vascularity in organs and
      skeletal tissues was increased as was induction of vascularity in response to
      femoral artery ligation. Our results indicate that STC-1 can affect calcium
      homeostasis, bone and muscle mass and structure, and angiogenesis through effects
      on osteoblasts, osteoclasts, myoblasts/myocytes, and endothelial cells.

PMID- 12193585
TI  - Rickets in VDR null mice is secondary to decreased apoptosis of hypertrophic
      chondrocytes.
AB  - Both vitamin D deficiency and the absence of a functional vitamin D receptor
      (VDR) lead to a growth plate abnormality known as rickets. Prevention of abnormal
      mineral ion homeostasis by early institution of dietary therapy in VDR null mice
      prevents rickets, demonstrating that the VDR is not required for normal growth
      plate maturation. We, therefore, hypothesized that rickets, in the absence of a
      functional VDR, is due to impaired mineral ion homeostasis. Analyses of growth
      plate morphology in VDR null mice demonstrated normal resting and proliferating
      chondrocyte layers; however an expansion of the hypertrophic chondrocyte layer
      was present by 24 days of age. Because extracellular calcium has been shown to
      play a role in chondrocyte maturation, we addressed the hypothesis that
      hypocalcemia led to impaired chondrocyte differentiation. However, in situ
      hybridization analyses revealed normal expression of hypertrophic chondrocyte
      markers in the tibial growth plate of 24 day old VDR null mice, suggesting that
      the increase in the hypertrophic chondrocyte layer was not secondary to impaired
      differentiation. We then addressed whether expansion of the hypertrophic
      chondrocyte layer was secondary to increased proliferation or decreased
      apoptosis. BrdU labeling failed to demonstrate an increase in chondrocyte
      proliferation in the VDR null mice; however, apoptosis was markedly diminished in
      the late hypertrophic chondrocytes of the VDR null mice, suggesting that
      impairment in programmed cell death of these cells leads to the characteristic
      findings of rickets.

PMID- 12193586
TI  - Oligonucleotide microarray analysis of intact human pancreatic islets:
      identification of glucose-responsive genes and a highly regulated TGFbeta
      signaling pathway.
AB  - Human pancreatic islets are a major focus of diabetes research due to their key
      role in glucose homeostasis and their potential for transplantation in the
      treatment of type 1 diabetes. Currently, no comprehensive analysis of baseline or
      glucose-stimulated islet gene expression is available. Using oligonucleotide
      microarrays we analyzed isolated intact human islets incubated at low and high
      glucose. We identified approximately 6000 islet genes, several with clinical
      implications, as well as a number of glucose-regulated genes. Interestingly, two
      transforming growth factor beta (TGFbeta) superfamily members were highly
      regulated by glucose. One of them, PDF, was found to have a very high expression
      level compared to other TGFbeta superfamily members. Quantitative reverse
      transcriptase polymerase chain reaction confirmed these results and demonstrated
      that the highly expressed PDF was approximately 10-fold down- regulated by
      glucose while other TGFbeta superfamily members and target genes were up
      regulated. These results suggest that a highly regulated TGFbeta signaling
      cascade exists in human islets, and that PDF may play a central role in islet
      biology. Since TGFbeta is involved in differentiation and immune modulation, this
      novel pathway may link glucose metabolism, immune response and development of
      human islets. We report here the first gene expression profile of intact human
      islets. These and similar analyses will provide better understanding of human
      islet biology and enhance the development of novel diabetes therapies.

PMID- 12193587
TI  - Postnatal growth and circulating ACTH and cortisol concentrations during the
      first month of life in cloned lambs.
AB  - Recent studies have indicated that there is a decrease in perinatal survival of
      apparently normal animals produced by somatic-cell nuclear transfer. Here we
      report that the cortisol and adrenocorticotrophic hormone (ACTH) profiles of
      cloned lambs in the first 4 weeks of life are significantly different to that of
      control lambs. The growth of cloned lambs however was not different to controls.
      These findings demonstrate that endocrine development may be altered in
      apparently "normal" clones.

PMID- 12193588
TI  - RH70, a bidirectional RNA helicase, co-purifies with U1snRNP.
AB  - In this report, I describe the co-purification of a novel 70-kDa RNA helicase
      (RH70) and U1snRNP through six column steps. Peptide sequence analysis by mass
      spectrometry and Edman degradation revealed that RH70 is the previously reported
      DDX17. Biochemical characterization of RH70, obtained by partial separation from
      U1snRNP, yielded the following results. (a) RH70 mediates the unwinding of duplex
      RNA but not DNA in an ATP-dependent manner. (b) Both the RNA-dependent ATPase and
      RNA helicase activities of RH70 are highly specific for ATP, exhibiting an
      apparent K(m) of 0.5 mm. (c) RH70 catalyzes the unwinding of duplex RNA
      containing single-stranded regions at either the 5'- or 3'-end. Its association
      with U1snRNP and ATP specificity suggest a role for RH70 in pre-mRNA splicing, in
      particular, at the early stages of the splicing reaction involving U1snRNP.

PMID- 12193589
TI  - Crystal structure of the HNF4 alpha ligand binding domain in complex with
      endogenous fatty acid ligand.
AB  - HNF4 alpha is an orphan member of the nuclear receptor family with prominent
      functions in liver, gut, kidney and pancreatic beta cells. We have solved the x
      ray crystal structure of the HNF4 alpha ligand binding domain, which adopts a
      canonical fold. Two conformational states are present within each homodimer: an
      open form with alpha helix 12 (alpha 12) extended and collinear with alpha 10 and
      a closed form with alpha 12 folded against the body of the domain. Although the
      protein was crystallized without added ligands, the ligand binding pockets of
      both closed and open forms contain fatty acids. The carboxylic acid headgroup of
      the fatty acid ion pairs with the guanidinium group of Arg(226) at one end of the
      ligand binding pocket, while the aliphatic chain fills a long, narrow channel
      that is lined with hydrophobic residues. These findings suggest that fatty acids
      are endogenous ligands for HNF4 alpha and establish a framework for understanding
      how HNF4 alpha activity is enhanced by ligand binding and diminished by MODY1
      mutations.

PMID- 12193590
TI  - Characterization of a novel lipid-A from Rhizobium species Sin-1. A unique lipid
      A structure that is devoid of phosphate and has a glycosyl backbone consisting of
      glucosamine and 2-aminogluconic acid.
AB  - The structure of the lipid-A from Rhizobium species Sin-1, a nitrogen-fixing Gram
      negative bacterial symbiont of Sesbania, was determined by composition, nuclear
      magnetic resonance spectroscopic, and mass spectrometric analyses. The lipid-A
      preparation consisted of a mixture of structures due to differences in fatty
      acylation and in the glycosyl backbone. There were two different disaccharide
      backbones. One disaccharide consisted of a distal glucosaminosyl residue beta
      linked to position 6 of a proximal 2-aminoglucono-1,5-lactonosyl residue, and in
      the second disaccharide, the proximal residue was 2-amino-2,3-dideoxy-d-erythro
      hex-2-enono-1,5-lactone. For both disaccharides, the distal glucosamine was
      acylated at C-2' primarily with beta-hydroxypalmitate (beta-OHC16:0) which, in
      turn, was O-acylated with 27-hydroxyoctacosanoic acid. For some of the lipid-A
      molecules, the distal glucosaminosyl residue was also acylated at C-3' with beta
      hydroxymyristate (beta-OHC14:0), whereas other molecules were devoid of this acyl
      substituent. Both the 2-aminoglucono-1,5-lactonosyl and 2-amino-2,3-dideoxy-d
      erythro-hex-2-enono-1,5-lactonosyl residues were acylated at C-2, primarily with
      beta-OHC16:0. Minor amounts of lipid-A molecules contained beta-OHC14:0 at C-3
      and/or beta-hydroxystearate (beta-OHC18:0) or beta-hydroxyoctadecenoate (beta
      OHC18:1) as the C-2 and C-2' N-acyl substituents.

PMID- 12193591
TI  - Membrane protein insertion regulated by bringing electrostatic and hydrophobic
      interactions into play. A case study with the translocation domain of diphtheria
      toxin.
AB  - The study of the membrane insertion of the translocation domain of diphtheria
      toxin deepens our insight into the interactions between proteins and membranes.
      During cell intoxication, this domain undergoes a change from a soluble and
      folded state at alkaline pH to a functional membrane-inserted state at acid pH.
      We found that hydrophobic and electrostatic interactions occur in a sequential
      manner between the domain and the membrane during the insertion. The first step
      involves hydrophobic interactions by the C-terminal region. This is because of
      the pH-induced formation of a molten globule specialized for binding to the
      membrane. Accumulation of this molten globule follows a precise molecular
      mechanism adapted to the toxin function. The second step, as the pH decreases,
      leads to the functional inserted state. It arises from the changes in the balance
      of electrostatic attractions and repulsions between the N-terminal part and the
      membrane. Our study shows how the structural changes and the interaction with
      membranes of the translocation domain are finely tuned by pH changes to take
      advantage of the cellular uptake system.

PMID- 12193592
TI  - Evidence of functional modulation of the MEKK/JNK/cJun signaling cascade by the
      low density lipoprotein receptor-related protein (LRP).
AB  - Lipoprotein receptors, such as LRP, have been shown to assemble multiprotein
      complexes containing intracellular signaling molecules; however, in vivo, their
      signaling function is poorly understood. Using a novel LRP receptor fusion
      construct, a type I transmembrane protein chimera, termed sIgG-LRP (bearing the
      intracellular COOH-terminal tail of human LRP as recombinant fusion to a
      transmembrane region plus the extracellular IgG-F(c) domain), we here
      investigated LRP signal transduction specificity in intact cells. First and
      similar to activated alpha2-macroglobulin as agonist of endogenous LRP,
      expression of sIgG-LRP demonstrated significant apoptosis protection. Second and
      similar to alpha2-macroglobulin-induced endogenous LRP, sIgG-LRP is sufficient to
      negatively modulate mitogen-induced Elk-1 and cJun (but not NF-kappaB)
      transcriptional activity. Third, expression of sIgG-LRP also impaired cJun
      transactivation mediated by constitutive active mutants of Rac-1 and MEKK-1.
      Fourth and unexpectedly, sIgG-LRP expression was found to be associated with a
      marked enhancement of mitogen-induced cJun amino-terminal kinase (JNK)
      activation. Fifth, confocal microscopic examination and subcellular fractionation
      demonstrated that sIgG-LRP and JNK co-localize in transfected cells. Therefore,
      sIgG-LRP expression was found to significantly impair activation-induced
      translocation of JNK into the nucleus. Taken together, we here demonstrate that
      sIgG-LRP protein sequesters activated JNK into the plasma membrane compartment in
      intact cells, inhibiting nuclear activation of the JNK-dependent transcription
      factors Elk-1 and cJun.

PMID- 12193593
TI  - 5(S)-hydroxyeicosatetraenoic acid stimulates DNA synthesis in human microvascular
      endothelial cells via activation of Jak/STAT and phosphatidylinositol 3
      kinase/Akt signaling, leading to induction of expression of basic fibroblast
      growth factor 2.
AB  - To understand the role of eicosanoids in angiogenesis, we have studied the effect
      of lipoxygenase metabolites of arachidonic acid on human microvascular
      endothelial cell (HMVEC) DNA synthesis. Among the various lipoxygenase
      metabolites of arachidonic acid tested, 5(S)-hydroxyeicosatetraenoic acid (5(S)
      HETE) induced DNA synthesis in HMVEC. 5(S)-HETE also stimulated Jak-2, STAT-1,
      and STAT-3 tyrosine phosphorylation and STAT-3-DNA binding activity. Tyrphostin
      AG490, a specific inhibitor of Jak-2, significantly reduced tyrosine
      phosphorylation and DNA binding activity of STAT-3 and DNA synthesis induced by
      5(S)-HETE. In addition, 5(S)-HETE stimulated phosphatidylinositol 3-kinase (PI3
      kinase) activity and phosphorylation of its downstream targets Akt, p70S6K, and
      4E-BP1 and their effector molecules ribosomal protein S6 and eIF4E. LY294002 and
      rapamycin, potent inhibitors of PI3-kinase and mTOR, respectively, also blocked
      the DNA synthesis induced by 5(S)-HETE. Interestingly, AG490 attenuated 5(S)-HETE
      induced PI3-kinase activity and phosphorylation of Akt, p70S6K, ribosomal protein
      S6, 4E-BP1, and eIF4E. 5(S)-HETE induced the expression of basic fibroblast
      growth factor 2 (bFGF-2) in a Jak-2- and PI3-kinase-dependent manner. In
      addition, a neutralizing anti-bFGF-2 antibody completely blocked 5(S)-HETE
      induced DNA synthesis in HMVEC. Together these results suggest that 5(S)-HETE
      stimulates HMVEC growth via Jak-2- and PI3-kinase-dependent induction of
      expression of bFGF-2. These findings also reveal a cross-talk between Jak-2 and
      PI3-kinase in response to 5(S)-HETE in HMVEC.

PMID- 12193594
TI  - An unexpected requirement for phosphatidylethanolamine N-methyltransferase in the
      secretion of very low density lipoproteins.
AB  - Phosphatidylethanolamine N-methyltransferase (PEMT) catalyzes the conversion of
      phosphatidylethanolamine to phosphatidylcholine (PC). We investigated whether
      there was diminished secretion of lipoproteins from hepatocytes derived from mice
      that lacked PEMT (Pemt(-/-)) compared with Pemt(+/+) mice. Hepatocytes were
      incubated with 0.75 mm oleate, the media were harvested, and triacylglycerol
      (TG), PC, apolipoprotein (apo) B100, and apoB48 were isolated and quantified.
      Compared with hepatocytes from Pemt(+/+) mice, hepatocytes from Pemt(-/-) mice
      secreted 50% less TG, whereas secretion of PC was unaffected. Fractionation of
      the secreted lipoproteins on density gradients demonstrated that the decrease in
      TG was in the very low density lipoprotein (VLDL)/low density lipoprotein
      fractions. The secretion of apoB100 was decreased by approximately 70% in
      VLDLs/low density lipoproteins, whereas there was no significant decrease in
      apoB48 secretion in any fraction. Transfection of McArdle hepatoma cells (that
      lack PEMT) with PEMT cDNA enhanced secretion of TG in the VLDLs. Because the
      levels of PC in the hepatocytes and hepatoma cells were unaffected by the lack of
      PEMT expression, there appears to be an unexpected requirement for PEMT in the
      secretion of apoB100-containing VLDLs.

PMID- 12193595
TI  - Modulation of Smad2-mediated signaling by extracellular signal-regulated kinase.
AB  - Components of the transforming growth factor-beta and mitogen-activated protein
      kinase pathways interact in controlling cell growth and differentiation. We show
      that phosphorylation of Smad2, a mediator of the activin/transforming growth
      factor-beta signal, by activated extracellular signal-regulated kinase 1 (ERK1)
      increases the amount of Smad2 protein and leads to enhanced transcriptional
      activity. Epidermal growth factor increased phosphorylation of Smad2 in COS7
      cells, and Smad2-dependent transcription in a mink lung epithelial cell line,
      L17, was enhanced by co-transfection of a constitutively active MEK1. In
      addition, transfection of Smad2 mutants lacking ERK sites resulted in reduced
      transcription, whereas mutants that mimicked ERK phosphorylation stimulated
      transcription. The amount of Smad2 protein was increased by transfection with a
      constitutively active MEK1 and reduced by co-transfection with the ERK
      phosphatase, HVH2. The elevation of Smad2 protein levels was because of increased
      half-life and resulted in increased complex formation with Smad4. A site of ERK
      dependent phosphorylation on Smad2 was located to Thr(8), a site that overlaps
      with the calmodulin binding region. We show that calmodulin inhibits Smad2
      phosphorylation by ERK1, and overexpressing calmodulin, or stimulating calmodulin
      activity with ionomycin, reduces Smad2 levels. These findings suggest that the
      ERK pathway positively regulates Smad2 signaling by phosphorylating Smad2 and
      that negative regulation of Smad2 signaling by calmodulin is achieved in part by
      inhibiting this phosphorylation.

PMID- 12193596
TI  - Rhizobium sin-1 lipopolysaccharide (LPS) prevents enteric LPS-induced cytokine
      production.
AB  - Endotoxin (lipopolysaccharide (LPS)), a component of Gram-negative bacteria, is
      among the most potent proinflammatory substances known. The lipid-A region of
      this molecule initiates the production of multiple host-derived inflammatory
      mediators, including cytokines (e.g. tumor necrosis factor-alpha (TNFalpha)). It
      has been a continuous effort to identify methods of interfering with the
      interaction between enteric LPS and inflammatory cells using natural and
      synthetic LPS analogs. Some of these LPS analogs (e.g. Rhodobacter spheroides
      LPS/lipid-A derivatives) are antagonists in human cells but act as potent
      agonists with cells of other species. Data reported here indicate that
      structurally novel LPS from symbiotic, nitrogen-fixing bacteria found in
      association with the root nodules of legumes do not stimulate human monocytes to
      produce TNFalpha. Furthermore, LPS from one of these symbiotic bacterial species,
      Rhizobium sp. Sin-1, significantly inhibits the synthesis of TNFalpha by human
      cells incubated with Escherichia coli LPS. Rhizobium Sin-1 LPS exerts these
      effects by competing with E. coli LPS for binding to LPS-binding protein and by
      directly competing with E. coli LPS for binding to human monocytes. Rhizobial
      lipid-A differs significantly from previously characterized lipid-A analogs in
      phosphate content, fatty acid acylation patterns, and carbohydrate backbone.
      These structural differences define the rhizobial lipid-A compounds as a
      potentially novel class of LPS antagonists that might well serve as therapeutic
      agents for the treatment of Gram-negative sepsis.

PMID- 12193597
TI  - Activation of Bak, Bax, and BH3-only proteins in the apoptotic response to
      doxorubicin.
AB  - The anthracyclin doxorubicin (DXR) is a major antitumor agent known to cause
      cellular damage via a number of mechanisms including free radical formation and
      inhibition of topoisomerase II. It is not clear, however, how the subsequent
      lesions may lead to the apoptotic death of the cell. We have here examined the
      effects of DXR on activation of pro-apoptotic members of the Bcl-2 family, all of
      which are connected to the mitochondrial events of apoptosis. In two human cell
      lines (lymphoma and myeloma), clinically relevant concentrations of DXR were
      found to induce apoptosis, first observed after 24 h of treatment. Apoptosis
      correlated with modulation of Bak and Bax to their active conformations. bax- as
      well as bak-deficient mouse embryo fibroblasts were resistant to DXR compared
      with wild-type mouse embryo fibroblasts further supporting a role for these
      proteins as main DXR-induced apoptosis regulators. Furthermore, using
      immunocytochemistry as well as chemical blocking of putative apical pathways we
      could demonstrate that Bak is activated prior to Bax. In the human cell lines,
      DXR was furthermore found to induce high protein levels of Bik, another BH3-only
      protein. DXR-induced apoptosis was completely blocked in Bcl-2-overexpressing
      U266 cells. Interestingly, in Bcl-2-transfected cells Bak activation was also
      blocked, while Bax was still partially active in agreement with differential
      regulation of these two proteins. Furthermore, co-incubation of the
      phosphatidylinositol 3-kinase (PI3K)-inhibitor LY294002 potentiated the apoptotic
      response to DXR. This enhanced apoptosis was preceded by enhanced Bak and Bax
      activation, and both responses as well as apoptosis were blocked in transfectants
      overexpressing Bcl-2. In summary, several pieces of evidence suggest that DXR
      induces apoptosis through a sequential and differential activation of Bak and
      Bax.

PMID- 12193598
TI  - Identification of a Ras palmitoyltransferase in Saccharomyces cerevisiae.
AB  - Most Ras proteins are posttranslationally modified by a palmitoyl lipid moiety
      through a thioester linkage. However, the mechanism by which this occurs is not
      known. Here, evidence is presented that the Ras2 protein of Saccharomyces
      cerevisiae is palmitoylated by a Ras protein acyltransferase (Ras PAT) encoded by
      the ERF2 and ERF4 genes. Erf2p is a 41-kDa protein localized to the membrane of
      the endoplasmic reticulum and contains a conserved DHHC cysteine-rich domain
      (DHHC-CRD). Erf2p co-purifies with Erf4p (26 kDa) when it is expressed in yeast
      or in Escherichia coli. The Erf2p/Erf4p complex is required for Ras PAT activity,
      and mutations within conserved residues (Cys(189), His(201), and Cys(203)) of the
      Erf2p DHHC-CRD domain abolish Ras PAT activity. Furthermore, a palmitoyl-Erf2p
      intermediate is detected suggesting that Erf2p is directly involved in palmitate
      transfer. ERF2 and ERF4 are the first genes identified that encode a
      palmitoyltransferase for a Ras GTPase.

PMID- 12193599
TI  - Regulation of cholesterol homeostasis and lipid metabolism in skeletal muscle by
      liver X receptors.
AB  - Recent studies have identified the liver X receptors (LXRalpha and LXRbeta) as
      important regulators of cholesterol and lipid metabolism. Although originally
      identified as liver-enriched transcription factors, LXRs are also expressed in
      skeletal muscle, a tissue that accounts for approximately 40% of human total body
      weight and is the major site of glucose utilization and fatty acid oxidation.
      Nevertheless, no studies have yet addressed the functional role of LXRs in
      muscle. In this work we utilize a combination of in vivo and in vitro analysis to
      demonstrate that LXRs can functionally regulate genes involved in cholesterol
      metabolism in skeletal muscle. Furthermore we show that treatment of muscle cells
      in vitro with synthetic agonists of LXR increases the efflux of intracellular
      cholesterol to extracellular acceptors such as high density lipoprotein, thus
      identifying this tissue as a potential important regulator of reverse cholesterol
      transport and high density lipoprotein levels. Additionally we demonstrate that
      LXRalpha and a subset of LXR target genes are induced during myogenesis,
      suggesting a role for LXR-dependent signaling in the differentiation process.

PMID- 12193600
TI  - Structure of a novel P-superfamily spasmodic conotoxin reveals an inhibitory
      cystine knot motif.
AB  - Conotoxin gm9a, a putative 27-residue polypeptide encoded by Conus gloriamaris,
      was recently identified as a homologue of the "spasmodic peptide", tx9a, isolated
      from the venom of the mollusk-hunting cone shell Conus textile (Lirazan, M. B.,
      Hooper, D., Corpuz, G. P., Ramilo, C. A., Bandyopadhyay, P., Cruz, L. J., and
      Olivera, B. M. (2000) Biochemistry 39, 1583-1588). The C. gloriamaris spasmodic
      peptide has been synthesized, and the refolded polypeptide was shown to be
      biologically active using a mouse bioassay. The chemically synthesized gm9a
      elicited the same symptomatology described previously for natively folded tx9a,
      and gm9a and tx9a were of similar potency, implying that neither the two gamma
      carboxyglutamate (Gla) residues found in tx9a (Ser(8) and Ala(13) in gm9a) nor
      Gly(1) (Ser(1) in gm9a) are crucial for biological activity. We have determined
      the three-dimensional structure of gm9a in aqueous solution and demonstrated that
      the molecule adopts the well known inhibitory cystine knot motif constrained by
      three disulfide bonds involving Cys(2)-Cys(16), Cys(6)-Cys(18) and Cys(12)
      Cys(23). Based on the gm9a structure, the sites of Gla substitution in tx9a are
      in loops located on one surface of the molecule, which is unlikely to be involved
      directly in receptor binding. Because this is the first structure reported for a
      member of the newly defined P-superfamily conotoxins, a comparison has been made
      with structurally related conotoxins. This shows that the structural scaffold
      that characterizes the P-conotoxins has the greatest potential for exhibiting
      structural diversity among the robust inhibitory cystine knot-containing
      conotoxins, a finding that has implications for functional epitope mimicry and
      protein engineering.

PMID- 12193601
TI  - An ATP-binding cassette transporter is a major glycoprotein of sea urchin sperm
      membranes.
AB  - Sperm are terminally differentiated cells that undergo several membrane-altering
      events before fusion with eggs. One event, the sea urchin sperm acrosome reaction
      (AR), is blocked by the lectin wheat germ agglutinin (WGA). In an effort to
      identify proteins involved in the AR induction, the peptide sequence was obtained
      from a 220-kDa WGA-binding protein. Degenerate PCR and library screening resulted
      in the full-length deduced amino acid sequence of an ATP-binding cassette
      transporter, suABCA. The protein of 1,764 residues has two transmembrane regions,
      two nucleotide-binding domains, and is most closely related to the human ABC
      subfamily A member 3 transporter (ABCA3). Sequence analysis suggests a large
      extracellular loop between transmembrane spanning segments 7 and 8, with five N
      linked glycosylation sites. An antibody made to the loop region binds to non
      permeabilized cells, supporting that this region is extracellular. suABCA is
      found in sperm membrane vesicles, it can be solubilized with nonionic detergents,
      and it shifts from 220 to 200 kDa upon protein:N-glycanase F digestion. suABCA
      localizes to the entire surface of sperm in a punctate pattern, but is not
      detected in lipid rafts. Based on its relationship to subfamily A, suABCA is most
      likely involved in phospholipid or cholesterol transport. This is the first
      investigation of an ABC transporter in animal sperm.

PMID- 12193602
TI  - Probing the molecular basis for potent and selective protein-tyrosine phosphatase
      1B inhibition.
AB  - Protein-tyrosine phosphatases (PTPs) are important for the control of proper
      cellular tyrosine phosphorylation. Despite the large number of PTPs encoded in
      the human genome and the emerging roles played by PTPs in human diseases, a
      detailed understanding of the role played by PTPs in normal physiology and in
      pathogenic conditions has been hampered by the absence of PTP-specific
      inhibitors. Such inhibitors could serve as useful tools for determining the
      physiological functions of PTPs and may constitute valuable therapeutics in the
      treatment of several human diseases. However, because of the highly conserved
      nature of the active site, it has been difficult to develop selective PTP
      inhibitors. By taking an approach to tether together two small ligands that can
      interact simultaneously with the active site and a unique proximal noncatalytic
      site, we have recently acquired Compound 2 (see Fig. 1), the most potent and
      selective PTP1B inhibitor identified to date, which exhibits several orders of
      magnitude selectivity in favor of PTP1B against a panel of PTPs. We describe an
      evaluation of the interaction between 2 and its analogs with PTP1B and its site
      directed mutants selected based on hydrogen/deuterium exchange of PTP1B backbone
      amides in the presence and absence of 2. We have established the binding mode of
      Compound 2 and identified 12 PTP1B residues that are important for the potency
      and selectivity of Compound 2. Although many of the residues important for
      Compound 2 binding are not unique to PTP1B, the combinations of all contact
      residues differ between PTP isozymes, which suggest that the binding surface
      defined by these residues in individual PTPs determines inhibitor selectivity.
      Our results provide structural information toward understanding of the molecular
      basis for potent and selective PTP1B inhibition and further establish the
      feasibility of acquiring potent, yet highly selective, PTP inhibitory agents.

PMID- 12193603
TI  - The SUMO ubiquitin-protein isopeptide ligase family member Miz1/PIASxbeta /Siz2
      is a transcriptional cofactor for TFII-I.
AB  - We have shown previously that a TFII-I-related protein, hMusTRD1/BEN, represses
      transcriptional activity of TFII-I. The repression by hMusTRD1/BEN was
      hypothesized to occur via a two-step competition mechanism involving a
      cytoplasmic shuttling factor and a nuclear cofactor required for transcriptional
      activation of TFII-I. Employing a two-hybrid approach with both yeast genomic and
      mouse cDNA libraries in parallel, we have identified the RING-like zinc finger
      containing Miz1/PIASxbeta/Siz2, which is a ubiquitin-protein isopeptide ligase in
      the SUMO pathway, as the potential nuclear cofactor that interacts with both TFII
      I and hMusTRD1/BEN. Our conclusion is based on the following observations. First,
      the interactions are biochemically confirmed in mammalian cells where
      Miz1/mPIASxbeta interacts with both TFII-I and hMusTRD1/BEN when these proteins
      are ectopically co-expressed. Second, co-expression of a nuclear localization
      signal-deficient mutant of Miz1/mPIASxbeta with wild type TFII-I fails to alter
      the subcellular localization of the former. Finally, ectopically expressed
      Miz1/mPIASxbeta augments the transcriptional activity of TFII-I and relieves the
      repression exerted by a mutant hMusTRD1/BEN that co-localized with TFII-I in the
      nucleus.

PMID- 12193604
TI  - Randomization of the entire active-site helix alpha 1 of the thiol-disulfide
      oxidoreductase DsbA from Escherichia coli.
AB  - DsbA from Escherichia coli is the most oxidizing member of the thiol-disulfide
      oxidoreductase family (E(o)' = -122 mV) and is required for efficient disulfide
      bond formation in the periplasm. The reactivity of the catalytic disulfide bond
      (Cys(30)-Pro(31)-His(32)-Cys(33)) is primarily due to an extremely low pK(a)
      value (3.4) of Cys(30), which is stabilized by the partial positive dipole charge
      of the active-site helix alpha1 (residues 30-37). We have randomized all non
      cysteine residues of helix alpha1 (residues 31, 32, and 34-37) and found that two
      thirds of the resulting variants complement DsbA deficiency in a dsbA deletion
      strain. Sequencing of 98 variants revealed a large number of non-conservative
      replacements in active variants, even at well conserved positions. This indicates
      that tertiary structure context strongly determines alpha-helical secondary
      structure formation of the randomized sequence. A subset of active and inactive
      variants was further characterized. All these variants were more reducing than
      wild type DsbA, but the redox potentials of active variants did not drop below 
      210 mV. All inactive variants had redox potentials lower than -210 mV, although
      some of the inactive proteins were still re-oxidized by DsbB. This demonstrates
      that efficient oxidation of substrate polypeptides is the crucial property of
      DsbA in vivo.

PMID- 12193605
TI  - Quaternary organization of the goodpasture autoantigen, the alpha 3(IV) collagen
      chain. Sequestration of two cryptic autoepitopes by intrapromoter interactions
      with the alpha4 and alpha5 NC1 domains.
AB  - Goodpasture's (GP) disease is caused by autoantibodies that target the alpha3(IV)
      collagen chain in the glomerular basement membrane (GBM). Goodpasture
      autoantibodies bind two conformational epitopes (E(A) and E(B)) located within
      the non-collagenous (NC1) domain of this chain, which are sequestered within the
      NC1 hexamer of the type IV collagen network containing the alpha3(IV),
      alpha4(IV), and alpha5(IV) chains. In this study, the quaternary organization of
      these chains and the molecular basis for the sequestration of the epitopes were
      investigated. This was accomplished by physicochemical and immunochemical
      characterization of the NC1 hexamers using chain-specific antibodies. The
      hexamers were found to have a molecular composition of
      (alpha3)(2)(alpha4)(2)(alpha5)(2) and to contain cross-linked alpha3-alpha5
      heterodimers and alpha4-alpha4 homodimers. Together with association studies of
      individual NC1 domains, these findings indicate that the alpha3, alpha4, and
      alpha5 chains occur together in the same triple-helical protomer. In the GBM,
      this protomer dimerizes through NC1-NC1 domain interactions such that the alpha3,
      alpha4, and alpha5 chains of one protomer connect with the alpha5, alpha4, and
      alpha3 chains of the opposite protomer, respectively. The immunodominant
      Goodpasture autoepitope, located within the E(A) region, is sequestered within
      the alpha3alpha4alpha5 protomer near the triple-helical junction, at the
      interface between the alpha3NC1 and alpha5NC1 domains, whereas the E(B) epitope
      is sequestered at the interface between the alpha3NC1 and alpha4NC1 domains. The
      results also reveal the network distribution of the six chains of collagen IV in
      the renal glomerulus and provide a molecular explanation for the absence of the
      alpha3, alpha4, alpha5, and alpha6 chains in Alport syndrome.

PMID- 12193606
TI  - Regulation of GTP-binding protein alpha q (Galpha q) signaling by the ezrin
      radixin-moesin-binding phosphoprotein-50 (EBP50).
AB  - Although ezrin-radixin-moesin-binding phosphoprotein 50 (EBP50) is a PDZ domain
      containing protein known to bind to various channels, receptors, cytoskeletal
      elements, and cytoplasmic proteins, there is still very little evidence for a
      role of EBP50 in the regulation of receptor signal transduction. In this report,
      we show that EBP50 inhibits the phospholipase C (PLC)-beta-mediated inositol
      phosphate production of a Galpha(q)-coupled receptor as well as PLC-beta
      activation by the constitutively active Galpha(q)-R183C mutant.
      Coimmunoprecipitation experiments revealed that EBP50 interacts with Galpha(q)
      and to a greater extent with Galpha(q)-R183C. Agonist stimulation of the
      thromboxane A(2) receptor (TP receptor) resulted in an increased interaction
      between EBP50 and Galpha(q), suggesting that EBP50 preferentially interacts with
      activated Galpha(q). We also demonstrate that EBP50 inhibits Galpha(q) signaling
      by preventing the interaction between Galpha(q) and the TP receptor and between
      activated Galpha(q) and PLC-beta1. Investigation of the EBP50 regions involved in
      Galpha(q) binding indicated that its two PDZ domains are responsible for this
      interaction. This study constitutes the first demonstration of an interaction
      between a G protein alpha subunit and another protein through a PDZ domain, with
      broad implications in the regulation of diverse physiological systems.

PMID- 12193607
TI  - Importance of glutamate 279 for the coenzyme binding of human glutamate
      dehydrogenase.
AB  - Although the structure of glutamate dehydrogenase (GDH) has been reported from
      various sources including mammalian GDH, there are conflicting views regarding
      the location and mechanism of actions of the coenzyme binding. We have expanded
      these speculations by photoaffinity labeling and cassette mutagenesis.
      Photoaffinity labeling with a specific probe, [(32)P]nicotinamide 2
      azidoadenosine dinucleotide, was used to identify the NAD(+) binding site within
      human GDH encoded by the synthetic human GDH gene and expressed in Escherichia
      coli as a soluble protein. Photolabel-containing peptides generated with trypsin
      were isolated by immobilized boronate affinity chromatography. Photolabeling of
      these peptides was most effectively prevented by the presence of NAD(+) during
      photolysis, demonstrating a selectivity of the photoprobe for the NAD(+) binding
      site. Amino acid sequencing and compositional analysis identified Glu(279) as the
      site of photoinsertion into human GDH, suggesting that Glu(279) is located at or
      near the NAD(+) binding site. The importance of the Glu(279) residue in the
      binding of NAD(+) was further examined by cassette mutagenesis with mutant
      enzymes containing Arg, Gly, Leu, Met, or Tyr at position 279. The mutagenesis at
      Glu(279) has no effects on the expression or stability of the different mutants.
      The K(m) values for NAD(+) were 10-14-fold greater for the mutant GDHs than for
      wild-type GDH, whereas the V(max) values were similar for wild-type and mutant
      GDHs. The efficiency (k(cat)/K(m)) of the mutant GDH was reduced up to 18-fold.
      The decreased efficiency of the mutants results from the increase in K(m) values
      for NAD(+). In contrast to the K(m) values for NAD(+), wild-type and mutant GDHs
      show similar K(m) values for glutamate, indicating that substitution at position
      279 had no appreciable effect on the affinity of enzyme for glutamate. There were
      no differences in sensitivities to ADP activation and GTP inhibition between wild
      type and mutant GDH, suggesting that Glu(279) is not directly involved in
      allosteric regulation. The results with photoaffinity labeling and cassette
      mutagenesis studies suggest that Glu(279) plays an important role for efficient
      binding of NAD(+) to human GDH.

PMID- 12193608
TI  - A conserved domain in the NH2 terminus important for assembly and functional
      expression of pacemaker channels.
AB  - Pacemaker channels are formed by co-assembly of hyperpolarization-activated
      cyclic nucleotide-gated (HCN) subunits. Previously, we suggested that the NH(2)
      termini of the mouse HCN2 isoform were important for subunit co-assembly and
      functional channel expression. Using an alignment strategy together with yeast
      two-hybrid assays, patch clamp electrophysiology, and confocal imaging, we have
      now identified a domain within the NH(2) terminus of the HCN2 subunit that is
      responsible for interactions between NH(2) termini and promoting the trafficking
      of functional channels to the plasma membrane. This domain is composed of 52
      amino acids, is located adjacent to the putative first transmembrane segment, and
      is highly conserved among the mammalian HCN isoforms. This conserved domain, but
      not the remaining unconserved NH(2)-terminal regions of HCN2, specifically
      interacted with itself in yeast two-hybrid assays. Moreover, the conserved domain
      was important for expression of currents. Whereas relatively normal whole cell
      HCN2 currents were produced by channels containing only the conserved domain,
      further deletion of this region, leaving only a more polar and putative coiled
      coil segment, eliminated HCN2 currents and resulted in proteins that localized
      predominantly in perinuclear compartments. Thus, we suggest that this conserved
      domain is the critical NH(2)-terminal determinant of subunit co-assembly and
      trafficking of pacemaker channels.

PMID- 12193609
TI  - A genetically economical family of plasmid-encoded transcriptional repressors
      involved in control of plasmid copy number.

PMID- 12193610
TI  - N4 RNA polymerase II, a heterodimeric RNA polymerase with homology to the single
      subunit family of RNA polymerases.
AB  - Bacteriophage N4 middle genes are transcribed by a phage-coded, heterodimeric,
      rifampin-resistant RNA polymerase, N4 RNA polymerase II (N4 RNAPII). Sequencing
      and transcriptional analysis revealed that the genes encoding the two subunits
      comprising N4 RNAPII are translated from a common transcript initiating at the N4
      early promoter Pe3. These genes code for proteins of 269 and 404 amino acid
      residues with sequence similarity to the single-subunit, phage-like RNA
      polymerases. The genes encoding the N4 RNAPII subunits, as well as a synthetic
      construct encoding a fusion polypeptide, have been cloned and expressed. Both the
      individually expressed subunits and the fusion polypeptide reconstitute
      functional enzymes in vivo and in vitro.

PMID- 12193611
TI  - Comparative proteome analysis of Brucella melitensis vaccine strain Rev 1 and a
      virulent strain, 16M.
AB  - The genus Brucella consists of bacterial pathogens that cause brucellosis, a
      major zoonotic disease characterized by undulant fever and neurological disorders
      in humans. Among the different Brucella species, Brucella melitensis is
      considered the most virulent. Despite successful use in animals, the vaccine
      strains remain infectious for humans. To understand the mechanism of virulence in
      B. melitensis, the proteome of vaccine strain Rev 1 was analyzed by two
      dimensional gel electrophoresis and compared to that of virulent strain 16M. The
      two strains were grown under identical laboratory conditions. Computer-assisted
      analysis of the two B. melitensis proteomes revealed proteins expressed in either
      16M or Rev 1, as well as up- or down-regulation of proteins specific for each of
      these strains. These proteins were identified by peptide mass fingerprinting. It
      was found that certain metabolic pathways may be deregulated in Rev 1. Expression
      of an immunogenic 31-kDa outer membrane protein, proteins utilized for iron
      acquisition, and those that play a role in sugar binding, lipid degradation, and
      amino acid binding was altered in Rev 1.

PMID- 12193612
TI  - SpiC is required for translocation of Salmonella pathogenicity island 2 effectors
      and secretion of translocon proteins SseB and SseC.
AB  - The Salmonella pathogenicity island 2 (SPI2) type III secretion system (TTSS)
      promotes Salmonella enterica serovar Typhimurium virulence for mice and increased
      survival and replication within eukaryotic cells. After phagocytosis, Salmonella
      serovar Typhimurium assembles the SPI2 TTSS to translocate over a dozen effector
      proteins across the phagosome membrane. SpiC has been previously shown to be a
      translocated effector with a large contribution to virulence (K. Uchiya, M. A.
      Barbieri, K. Funato, A. H. Shah, P. D. Stahl, and E. A. Groisman, EMBO J. 18:3924
      3933, 1999). This report demonstrates by competitive index that the virulence
      phenotype of a spiC mutant is equivalent to that of a secretion component mutant.
      In addition, translocation of SPI2 effector proteins was shown to require SpiC.
      Thus, the severe virulence phenotype resulting from deletion of spiC is likely
      due to the inability to translocate all SPI2 effectors. SpiC was also required to
      secrete translocon proteins SseB and SseC but not translocated effector SseJ,
      indicating that lack of assembly of the translocon explains the spiC mutant
      phenotype.

PMID- 12193614
TI  - Purification and polar localization of pneumococcal LytB, a putative endo-beta-N
      acetylglucosaminidase: the chain-dispersing murein hydrolase.
AB  - The DNA region encoding the mature form of a pneumococcal murein hydrolase (LytB)
      was cloned and expressed in Escherichia coli. LytB was purified by affinity
      chromatography, and its activity was suggested to be the first identified endo
      beta-N-acetylglucosaminidase of Streptococcus pneumoniae. LytB can remove a
      maximum of only 25% of the radioactivity from [(3)H]choline-labeled pneumococcal
      cell walls in in vitro assays. Inactivation of the lytB gene of wild-type strain
      R6 (R6B mutant) led to the formation of long chains but did not affect either
      total cell wall hydrolytic activity at the stationary phase of growth or
      development of genetic competence. Longer chains were formed when the lytB
      mutation was introduced into the M31 strain (M31B mutant), which harbors a
      complete deletion of lytA, which codes for the major autolysin. Furthermore, the
      use of this mutant revealed that LytB is the first nonautolytic murein hydrolase
      of pneumococcus. Purified LytB added to pneumococcal cultures of R6B or M31B was
      capable of dispersing, in a dose-dependent manner, the long chains characteristic
      of these mutants into diplococci or short chains, the typical morphology of R6
      and M31 strains, respectively. In vitro acetylation of purified pneumococcal cell
      walls did not affect the activity of LytB, whereas that of the LytA amidase was
      drastically reduced. On the other hand, the use of a translational fusion between
      the gene (gfp) coding for the green fluorescent protein (GFP) and lytB supports
      the notion that LytB accumulates in the cell poles of either the wild-type R6,
      lytB mutants, or ethanolamine-containing cells (EA cells). The GFP-LytB fusion
      protein was also able to unchain the lytB mutants but not the EA cells. In
      contrast, translational fusion protein GFP-LytA preferentially bound to the
      equatorial regions of choline-containing cells but did not affect their average
      chain length. These observations suggest the existence of specific receptors for
      LytB that are positioned at the polar region on the pneumococcal surface,
      allowing localized peptidoglycan hydrolysis and separation of the daughter cells.

PMID- 12193613
TI  - Conserved amplification of chemotactic responses through chemoreceptor
      interactions.
AB  - Many bacteria concentrate their chemoreceptors at the cell poles. Chemoreceptor
      location is important in Escherichia coli, since chemosensory responses are
      sensitive to receptor proximity. It is not known, however, whether chemotaxis in
      other bacteria is similarly regulated. To investigate the importance of receptor
      receptor interactions in other bacterial species, we synthesized saccharide
      bearing multivalent ligands that are designed to cluster relevant chemoreceptors.
      As has been shown with E. coli, we demonstrate that the behaviors of Bacillus
      subtilis, Spirochaete aurantia, and Vibrio furnissii are sensitive to the valence
      of the chemoattractant. Moreover, in B. subtilis, chemotactic responses to serine
      were increased by pretreatment with saccharide-bearing multivalent ligands. This
      result indicates that, as in E. coli, signaling information is transferred among
      chemoreceptors in B. subtilis. These results suggest that interreceptor
      communication may be a general mechanism for modulating chemotactic responses in
      bacteria.

PMID- 12193615
TI  - Mycobacterium smegmatis L-alanine dehydrogenase (Ald) is required for proficient
      utilization of alanine as a sole nitrogen source and sustained anaerobic growth.
AB  - NAD(H)-dependent L-alanine dehydrogenase (EC 1.4.1.1) (Ald) catalyzes the
      oxidative deamination of L-alanine and the reductive amination of pyruvate. To
      assess the physiological role of Ald in Mycobacterium smegmatis, we cloned the
      ald gene, identified its promoter, determined the protein expression levels, and
      analyzed the combined effects of nutrient supplementation, oxygen availability,
      and growth stage on enzyme activity. High Ald activities were observed in cells
      grown in the presence of L- or D-alanine regardless of the oxygen availability
      and growth stage. In exponentially growing cells under aerobic conditions,
      supplementation with alanine resulted in a 25- to 50-fold increase in the enzyme
      activity. In the absence of alanine supplementation, 23-fold-higher Ald
      activities were observed in cells grown exponentially under anaerobic conditions.
      Furthermore, M. smegmatis ald null mutants were constructed by targeted
      disruption and were shown to lack any detectable Ald activity. In contrast, the
      glycine dehydrogenase (EC 1.4.1.10) (Gdh) activity in mutant cells remained at
      wild-type levels, indicating that another enzyme protein is responsible for the
      physiologically relevant reductive amination of glyoxylate. The ald mutants grew
      poorly in minimal medium with L-alanine as the sole nitrogen source, reaching a
      saturation density 100-fold less than that of the wild-type strain. Likewise,
      mutants grew to a saturation density 10-fold less than that of the wild-type
      strain under anaerobic conditions. In summary, the phenotypes displayed by the M.
      smegmatis ald mutants suggest that Ald plays an important role in both alanine
      utilization and anaerobic growth.

PMID- 12193617
TI  - Carbonic anhydrase is essential for growth of Ralstonia eutropha at ambient CO(2)
      concentrations.
AB  - Mutant strain 25-1 of the facultative chemoautotroph Ralstonia eutropha H16 had
      previously been shown to exhibit an obligately high-CO(2)-requiring (HCR)
      phenotype. Although the requirement varied with the carbon and energy sources
      utilized, none of these conditions allowed growth at the air concentration of
      CO(2). In the present study, a gene designated can and encoding a beta-carbonic
      anhydrase (CA) was identified as the site altered in strain 25-1. The mutation
      caused a replacement of the highly conserved glycine residue 98 by aspartate in
      Can. A can deletion introduced into wild-type strain H16 generated mutant HB1,
      which showed the same HCR phenotype as mutant 25-1. Overexpression of can in
      Escherichia coli and mass spectrometric determination of CA activity demonstrated
      that can encodes a functional CA. The enzyme is inhibited by ethoxyzolamide and
      requires 40 mM MgSO(4) for maximal activity. Low but significant CA activities
      were detected in wild-type H16 but not in mutant HB1, strongly suggesting that
      the CA activity of Can is essential for growth of the wild type in the presence
      of low CO(2) concentrations. The HCR phenotype of HB1 was overcome by
      complementation with heterologous CA genes, indicating that growth of the
      organism at low CO(2) concentrations requires sufficient CA activity rather than
      the specific function of Can. The metabolic function(s) depending on CA activity
      remains to be identified.

PMID- 12193616
TI  - prbA, a gene coding for an esterase hydrolyzing parabens in enterobacter cloacae
      and Enterobacter gergoviae strains.
AB  - The new gene prbA encodes an esterase responsible for the hydrolysis of the ester
      bond of parabens in Enterobacter cloacae strain EM. This gene is located on the
      chromosome of strain EM and was cloned by several PCR approaches. The prbA gene
      codes for an immature protein of 533 amino acids, the first 31 of which represent
      a proposed signal peptide yielding a mature protein of a putative molecular mass
      of 54.6 kDa. This enzyme presents analogies with other type B carboxylesterases,
      mainly of eukaryotic origin. The cloning and expression of the prbA gene in a
      strain of Escherichia coli previously unable to hydrolyze parabens resulted in
      the acquisition of a hydrolytic capacity comparable to the original activity of
      strain EM, along with an increased resistance of the transformed strain to methyl
      paraben. The presence of homologues of prbA was tested in additional ubiquitous
      bacteria, which may be causative factors in opportunistic infections, including
      Enterobacter gergoviae, Enterobacter aerogenes, Pseudomonas agglomerans, E. coli,
      Pseudomonas aeruginosa, and Burkholderia cepacia. Among the 41 total strains
      tested, 2 strains of E. gergoviae and 1 strain of Burkholderia cepacia were able
      to degrade almost completely 800 mg of methyl paraben liter(-1). Two strains of
      E. gergoviae, named G1 and G12, contained a gene that showed high homology to the
      prbA gene of E. cloacae and demonstrated comparable paraben esterase activities.
      The significant geographical distance between the locations of the isolated E.
      cloacae and E. gergoviae strains suggests the possibility of an efficient
      transfer mechanism of the prbA gene, conferring additional resistance to parabens
      in ubiquitous bacteria that represent a common source of opportunistic
      infections.

PMID- 12193618
TI  - A novel histidine-rich CPx-ATPase from the filamentous cyanobacterium
      Oscillatoria brevis related to multiple-heavy-metal cotolerance.
AB  - A novel gene related to heavy-metal transport was cloned and identified from the
      filamentous cyanobacterium Oscillatoria brevis. Sequence analysis of the gene
      (the Bxa1 gene) showed that its product possessed high homology with heavy-metal
      transport CPx-ATPases. The CPC motif, which is proposed to form putative cation
      transduction channel, was found in the sixth transmembrane helix. However,
      instead of the CXXC motif that is present in the N termini of most metal
      transport CPx-ATPases, Bxa1 contains a unique Cys-Cys (CC) sequence element and
      histidine-rich motifs as a putative metal binding site. Northern blotting and
      real-time quantitative reverse transcription-PCR showed that expression of Bxa1
      mRNA was induced in vivo by both monovalent (Cu(+) and Ag(+)) and divalent
      (Zn(2+) and Cd(2+)) heavy-metal ions at similar levels. Experiments on heavy
      metal tolerance in Escherichia coli with recombinant Bxa1 demonstrated that Bxa1
      conferred resistance to both monovalent and divalent heavy metals. This is the
      first report of a CPx-ATPase responsive to both monovalent and divalent heavy
      metals.

PMID- 12193620
TI  - Isoprenoid biosynthesis in Synechocystis sp. strain PCC6803 is stimulated by
      compounds of the pentose phosphate cycle but not by pyruvate or deoxyxylulose-5
      phosphate.
AB  - The photosynthetic cyanobacterium Synechocystis sp. strain PCC6803 possesses
      homologs of known genes of the non-mevalonate 2-C-methyl-D-erythritol 2-phosphate
      (MEP) pathway for synthesis of isopentenyl diphosphate (IPP) and dimethylallyl
      diphosphate (DMAPP). Isoprenoid biosynthesis in extracts of this cyanobacterium,
      measured by incorporation of radiolabeled IPP, was not stimulated by pyruvate, an
      initial substrate of the MEP pathway in Escherichia coli, or by deoxyxylulose-5
      phosphate, the first pathway intermediate in E. coli. However, high rates of IPP
      incorporation were obtained with addition of dihydroxyacetone phosphate (DHAP)
      and glyceraldehyde 3-phosphate (GA3P), as well as a variety of pentose phosphate
      cycle compounds. Fosmidomycin (at 1 micro M and 1 mM), an inhibitor of
      deoxyxylulose-5-phosphate reductoisomerase, did not significantly inhibit
      phototrophic growth of the cyanobacterium, nor did it affect [(14)C]IPP
      incorporation stimulated by DHAP plus GA3P. To date, it has not been possible to
      unequivocally demonstrate IPP isomerase activity in this cyanobacterium. The
      combined results suggest that the MEP pathway, as described for E. coli, is not
      the primary path by which isoprenoids are synthesized under photosynthetic
      conditions in Synechocystis sp. strain PCC6803. Our data support alternative
      routes of entry of pentose phosphate cycle substrates derived from
      photosynthesis.

PMID- 12193621
TI  - Mutational eidence for a functional connection between two domains of 23S rRNA in
      translation termination.
AB  - Nucleotide 1093 in domain II of Escherichia coli 23S rRNA is part of a highly
      conserved structure historically referred to as the GTPase center. The mutation
      G1093A was previously shown to cause readthrough of nonsense codons and high
      temperature-conditional lethality. Defects in translation termination caused by
      this mutation have also been demonstrated in vitro. To identify sites in 23S rRNA
      that may be functionally associated with the G1093 region during termination, we
      selected for secondary mutations in 23S rRNA that would compensate for the
      temperature-conditional lethality caused by G1093A. Here we report the isolation
      and characterization of such a secondary mutation. The mutation is a deletion of
      two consecutive nucleotides from helix 73 in domain V, close to the
      peptidyltransferase center. The deletion results in a shortening of the CGCG
      sequence between positions 2045 and 2048 by two nucleotides to CG. In addition to
      restoring viability in the presence of G1093A, this deletion dramatically
      decreased readthrough of UGA nonsense mutations caused by G1093A. An analysis of
      the amount of mutant rRNA in polysomes revealed that this decrease cannot be
      explained by an inability of G1093A-containing rRNA to be incorporated into
      polysomes. Furthermore, the deletion was found to cause UGA readthrough on its
      own, thereby implicating helix 73 in termination for the first time. These
      results also indicate the existence of a functional connection between the G1093
      region and helix 73 during translation termination.

PMID- 12193619
TI  - The MexJK efflux pump of Pseudomonas aeruginosa requires OprM for antibiotic
      efflux but not for efflux of triclosan.
AB  - Using the biocide triclosan as a selective agent, several triclosan-resistant
      mutants of a susceptible Pseudomonas aeruginosa strain were isolated. Cloning and
      characterization of a DNA fragment conferring triclosan resistance from one of
      these mutants revealed a hitherto uncharacterized efflux system of the resistance
      nodulation cell division (RND) family, which was named MexJK and which is encoded
      by the mexJK operon. Expression of this operon is negatively regulated by the
      product of mexL, a gene located upstream of and transcribed divergently from
      mexJK. The triclosan-resistant mutant contained a single nucleotide change in
      mexL, which caused an amino acid change in the putative helix-turn-helix domain
      of MexL. The MexL protein belongs to the TetR family of repressor proteins. The
      MexJK system effluxed tetracycline and erythromycin but only in the presence of
      the outer membrane protein channel OprM; OprJ and OprN did not function with
      MexJK. Triclosan efflux required neither of the outer membrane protein channels
      tested but necessitated the MexJ membrane fusion protein and the MexK inner
      membrane RND transporter. The results presented in this study suggest that MexJK
      may function as a two-component RND pump for triclosan efflux but must associate
      with OprM to form a tripartite antibiotic efflux system. Furthermore, the results
      confirm that triclosan is an excellent tool for the study of RND multidrug efflux
      systems and that this popular biocide therefore readily selects mutants which are
      cross-resistant with antibiotics.

PMID- 12193622
TI  - Temperature- and H-NS-dependent regulation of a plasmid-encoded virulence operon
      expressing Escherichia coli hemolysin.
AB  - Proteins H-NS and Hha form a nucleoprotein complex that modulates expression of
      the thermoregulated hly operon of Escherichia coli. We have been able to identify
      two H-NS binding sites in the hly regulatory region. One of them partially
      overlaps the promoter region (site II), and the other is located about 2 kbp
      upstream (site I). In contrast, Hha protein did not show any preference for
      specific sequences. In vitro, temperature influences the affinity of H-NS for a
      DNA fragment containing both binding sites and H-NS-mediated repression of hly
      operon transcription. Deletion analysis of the hly regulatory region confirms the
      relevance of site I for thermoregulation of this operon. We present a model to
      explain the temperature-modulated repression of the hly operon, based on the
      experiments reported here and other, preexisting data.

PMID- 12193623
TI  - A LuxR homolog controls production of symbiotically active extracellular
      polysaccharide II by Sinorhizobium meliloti.
AB  - Production of complex extracellular polysaccharides (EPSs) by the nitrogen-fixing
      soil bacterium Sinorhizobium meliloti is required for efficient invasion of root
      nodules on the host plant alfalfa. Any one of three S. meliloti polysaccharides,
      succinoglycan, EPS II, or K antigen, can mediate infection thread initiation and
      extension (root nodule invasion) on alfalfa. Of these three polysaccharides, the
      only symbiotically active polysaccharide produced by S. meliloti wild-type strain
      Rm1021 is succinoglycan. The expR101 mutation is required to turn on production
      of symbiotically active forms of EPS II in strain Rm1021. In this study, we have
      determined the nature of the expR101 mutation in S. meliloti. The expR101
      mutation, a spontaneous dominant mutation, results from precise, reading frame
      restoring excision of an insertion sequence from the coding region of expR, a
      gene whose predicted protein product is highly homologous to the Rhizobium
      leguminosarum bv. viciae RhiR protein and a number of other homologs of Vibrio
      fischeri LuxR that function as receptors for N-acylhomoserine lactones (AHLs) in
      quorum-sensing regulation of gene expression. S. meliloti ExpR activates
      transcription of genes involved in EPS II production in a density-dependent
      fashion, and it does so at much lower cell densities than many quorum-sensing
      systems. High-pressure liquid chromatographic fractionation of S. meliloti
      culture filtrate extracts revealed at least three peaks with AHL activity, one of
      which activated ExpR-dependent expression of the expE operon.

PMID- 12193625
TI  - Synergistic effects on crystalline cellulose degradation between cellulosomal
      cellulases from Clostridium cellulovorans.
AB  - Clostridium cellulovorans produces a multienzyme cellulose-degrading complex
      called the cellulosome. In this study, we determined the synergistic effects on
      crystalline cellulose degradation by three different recombinant cellulosomes
      containing either endoglucanase EngE, endoglucanase EngH, or exoglucanase ExgS
      bound to mini-CbpA, a part of scaffolding protein CbpA. EngE, EngH, and ExgS are
      classified into the glycosyl hydrolase families 5, 9, and 48, respectively. The
      assembly of ExgS and EngH with mini-CbpA increased the activity against insoluble
      cellulose 1.5- to 3-fold, although no effects on activity against soluble
      cellulose were observed. These results indicated that mini-CbpA could help
      cellulase components degrade insoluble cellulose but not soluble cellulose. The
      mixture of the cellulosomes containing ExgS and EngH showed higher activity and
      synergy degrees than the other cellulosome mixtures, indicating the synergistic
      effect between EngH and ExgS was the most dominant effect among the three
      mixtures for crystalline cellulose degradation. Reactions were also performed by
      adding different cellulosomes in a sequential manner. When ExgS was used for the
      initial reaction followed by EngE and EngH, almost no synergistic effect was
      observed. On the other hand, when EngE or EngH was used for the first reaction
      followed by ExgS, synergistic effects were observed. These results indicated that
      the initial reactions by EngH and/or EngE promoted cellulose degradation by ExgS.

PMID- 12193624
TI  - Role of ppGpp in rpoS stationary-phase regulation in Escherichia coli.
AB  - The bacterial sigma factor RpoS is strongly induced under a variety of stress
      conditions and during growth into stationary phase. Here, we used rpoS-lac
      fusions in Escherichia coli to investigate control acting at the level of RpoS
      synthesis, which is especially evident when cells approach stationary phase in
      rich medium. Previous work has shown that the small molecule ppGpp is required
      for normal levels of RpoS in stationary phase. Despite the attraction of a model
      in which the ppGpp level controls stationary-phase induction of RpoS, careful
      measurement of rpoS-lac expression in a mutant lacking ppGpp showed similar
      effects during both exponential growth and stationary phase; the main effect of
      ppGpp was on basal expression. In addition, a modest regulatory defect was
      associated with the mutant lacking ppGpp, delaying the time at which full
      expression was achieved by 2 to 3 h. Deletion analysis showed that the defect in
      basal expression was distributed over several sequence elements, while the
      regulatory defect mapped to the region upstream of the rpoS ribosome-binding site
      (RBS) that contains a cis-acting antisense element. A number of other genes that
      have been suggested as regulators of rpoS were tested, including dksA, dsrA,
      barA, ppkx, and hfq. With the exception of the dksA mutant, which had a modest
      defect in Luria-Bertani medium, none of these mutants was defective for rpoS
      stationary-phase induction. Even a short rpoS segment starting at 24 nucleotides
      upstream of the AUG initiation codon was sufficient to confer substantial
      stationary-phase regulation, which was mainly posttranscriptional. The effect of
      RBS-proximal sequence was independent of all known trans-acting factors,
      including ppGpp.

PMID- 12193626
TI  - Differential expression and localization of Mn and Fe superoxide dismutases in
      the heterocystous cyanobacterium Anabaena sp. strain PCC 7120.
AB  - Superoxide dismutases (Sods) play very important roles in preventing oxidative
      damages in aerobic organisms. The nitrogen-fixing heterocystous cyanobacterium
      Anabaena sp. strain PCC 7120 has two Sod-encoding genes: a sodB, encoding a
      soluble iron-containing Sod (FeSod), and a sodA, encoding a manganese-containing
      Sod (MnSod). The FeSod was purified and characterized. A recombinant FeSod was
      also obtained by overproduction in Escherichia coli. Immunoblot study of the
      FeSod during induction of heterocyst differentiation showed that the cells
      produced six- to eightfold more FeSod 8 h after a shift from a nitrogen-replete
      condition to a nitrogen-depleted condition. However, the amount of FeSod protein
      in filaments with mature heterocysts was the same as that in filaments grown with
      combined nitrogen. Superoxide anion-generating chemicals such as methyl viologen
      did not induce upregulation of the sodB gene expression. The predicted preprotein
      of the sodA gene has a leader peptide and a motif for membrane attachment at the
      N terminus of the mature protein. Activity staining after gel electrophoresis of
      the purified thylakoid membranes showed that most of the MnSod in Anabaena sp.
      strain PCC 7120 was located on thylakoids toward the lumenal side. Expression of
      the sodA gene in E. coli shows that the leader peptide was required for its
      activity and the membrane localization of the MnSod. Northern hybridization
      detected one 0.82-kb transcript of sodA. The sodA gene was upregulated by methyl
      viologen, whereas its amount was unchanged during heterocyst differentiation.
      Immunoblotting and activity staining showed that isolated heterocysts contained a
      lower but still significant amount of FeSod, suggesting that its function is
      required in heterocysts. No MnSod was observed in isolated heterocysts. These
      results show that the two different Sod proteins have differentiated roles in
      Anabaena sp. strain PCC 7120.

PMID- 12193627
TI  - Transposition of cyanobacterium insertion element ISY100 in Escherichia coli.
AB  - The genome of the cyanobacterium Synechocystis sp. strain PCC6803 has nine kinds
      of insertion sequence (IS) elements, of which ISY100 in 22 copies is the most
      abundant. A typical ISY100 member is 947 bp long and has imperfect terminal
      inverted repeat sequences. It has an open reading frame encoding a 282-amino-acid
      protein that appears to have partial homology with the transposase encoded by a
      bacterial IS, IS630, indicating that ISY100 belongs to the IS630 family. To
      determine whether ISY100 has transposition ability, we constructed a plasmid
      carrying the IPTG (isopropyl-beta-D-thiogalactopyranoside)-inducible transposase
      gene at one site and mini-ISY100 with the chloramphenicol resistance gene,
      substituted for the transposase gene of ISY100, at another site and introduced
      the plasmid into an Escherichia coli strain already harboring a target plasmid.
      Mini-ISY100 transposed to the target plasmid in the presence of IPTG at a very
      high frequency. Mini-ISY100 was inserted into the TA sequence and duplicated it
      upon transposition, as do IS630 family elements. Moreover, the mini-ISY100
      carrying plasmid produced linear molecules of mini-ISY100 with the exact 3' ends
      of ISY100 and 5' ends lacking two nucleotides of the ISY100 sequence. No
      bacterial insertion elements have been shown to generate such molecules, whereas
      the eukaryotic Tc1/mariner family elements, Tc1 and Tc3, which transpose to the
      TA sequence, have. These findings suggest that ISY100 transposes to a new site
      through the formation of linear molecules, such as Tc1 and Tc3, by excision. Some
      Tc1/mariner family elements leave a footprint with an extra sequence at the site
      of excision. No footprints, however, were detected in the case of ISY100,
      suggesting that eukaryotes have a system that repairs a double strand break at
      the site of excision by an end-joining reaction, in which the gap is filled with
      a sequence of several base pairs, whereas prokaryotes do not have such a system.
      ISY100 transposes in E. coli, indicating that it transposes without any host
      factor other than the transposase encoded by itself. Therefore, it may be able to
      transpose in other biological systems.

PMID- 12193628
TI  - Fe(2+)-tetracycline-mediated cleavage of the Tn10 tetracycline efflux protein
      TetA reveals a substrate binding site near glutamine 225 in transmembrane helix
      7.
AB  - TetA specified by Tn10 is a class B member of a group of related bacterial
      transport proteins of 12 transmembrane alpha helices that mediate resistance to
      the antibiotic tetracycline. A tetracycline-divalent metal cation complex is
      expelled from the cell in exchange for a entering proton. The site(s) where
      tetracycline binds to this export pump is not known. We found that, when chelated
      to tetracycline, Fe(2+) cleaved the backbone of TetA predominantly at a single
      position, glutamine 225 in transmembrane helix 7. The related class D TetA
      protein from plasmid RA1 was cut at exactly the same position. There was no
      cleavage with glycylcycline, an analog of tetracycline that does not bind to
      TetA. The Fe(2+)-tetracycline complex was not detectably transported by TetA.
      However, cleavage products of the same size as with Fe(2+) occurred with Co(2+),
      known to be cotransported with tetracycline. The known substrate Mg (2+)
      tetracycline interfered with cleavage by Fe(2+). These findings suggest that
      cleavage results from binding at a substrate-specific site. Fe(2+) is known to be
      able to cleave amide bonds in proteins at distances up to approximately 12 A. We
      conclude that the alpha carbon of glutamine 225 is probably within 12 A of the
      position of the Fe(2+) ion in the Fe(2+)-tetracycline complex bound to the
      protein.

PMID- 12193629
TI  - Role for phosphoglucomutase in Vibrio fischeri-Euprymna scolopes symbiosis.
AB  - Vibrio fischeri, a luminescent marine bacterium, specifically colonizes the light
      organ of its symbiotic partner, the Hawaiian squid Euprymna scolopes. In a screen
      for V. fischeri colonization mutants, we identified a strain that exhibited on
      average a 10-fold decrease in colonization levels relative to that achieved by
      wild-type V. fischeri. Further characterization revealed that this defect did not
      result from reduced luminescence or motility, two processes required for normal
      colonization. We determined that the transposon in this mutant disrupted a gene
      with high sequence identity to the pgm (phosphoglucomutase) gene of Escherichia
      coli, which encodes an enzyme that functions in both galactose metabolism and the
      synthesis of UDP-glucose. The V. fischeri mutant grew poorly with galactose as a
      sole carbon source and was defective for phosphoglucomutase activity, suggesting
      functional identity between E. coli Pgm and the product of the V. fischeri gene,
      which was therefore designated pgm. In addition, lipopolysaccharide profiles of
      the mutant were distinct from that of the parent strain and the mutant exhibited
      increased sensitivity to various cationic agents and detergents. Chromosomal
      complementation with the wild-type pgm allele restored the colonization ability
      to the mutant and also complemented the other noted defects. Unlike the pgm
      mutant, a galactose-utilization mutant (galK) of V. fischeri colonized juvenile
      squid to wild-type levels, indicating that the symbiotic defect of the pgm mutant
      is not due to an inability to catabolize galactose. Thus, pgm represents a new
      gene required for promoting colonization of E. scolopes by V. fischeri.

PMID- 12193631
TI  - Characterization of bcsA mutations that bypass two distinct signaling
      requirements for Myxococcus xanthus development.
AB  - The BsgA protease is required for starvation-induced development in Myxococcus
      xanthus. Bypass suppressors of a bsgA mutant were isolated to identify genes that
      may encode additional components of BsgA protease-dependent regulation of
      development. Strain M951 was isolated following Tn5 mutagenesis of a bsgA mutant
      and was capable of forming fruiting bodies and viable spores in the absence of
      the BsgA protease. The Tn5Omega951 insertion was localized to a gene, bcsA, that
      encodes a protein that has significant amino acid similarity to a group of
      recently described flavin-containing monooxygenases involved in styrene
      catabolism. Mutations in bcsA bypassed the developmental requirements for both
      extracellular B and C signaling but did not bypass the requirement for A
      signaling. Bypass of the B-signaling requirement by the bcsA mutation was
      accompanied by restored expression of a subset of developmentally induced lacZ
      fusions to the BsgA protease-deficient strain. bcsA mutant cells developed
      considerably faster than wild-type cells at low cell density and altered
      transcriptional levels of a developmentally induced, cell-density-regulated gene
      (Omega4427), suggesting that the bcsA gene product may normally act to inhibit
      development in a cell-density-regulated fashion. Bypass of the requirements for
      both B and C signaling by bcsA mutations suggests a possible link between these
      two genetically, biochemically, and temporally distinct signaling requirements.

PMID- 12193632
TI  - barS1, a gene for biosynthesis of a gamma-butyrolactone autoregulator, a
      microbial signaling molecule eliciting antibiotic production in Streptomyces
      species.
AB  - From Streptomyces virginiae, in which production of streptogramin antibiotic
      virginiamycin M(1) and S is tightly regulated by a low-molecular-weight
      Streptomyces hormone called virginiae butanolide (VB), which is a member of the
      gamma-butyrolactone autoregulators, the hormone biosynthetic gene (barS1) was
      cloned and characterized by heterologous expression in Escherichia coli and by
      gene disruption in S. virginiae. The barS1 gene (a 774-bp open reading frame
      encoding a 257-amino-acid protein [M(r), 27,095]) is situated in the 10-kb
      regulator island surrounding the VB-specific receptor gene, barA. The deduced
      BarS1 protein is weakly homologous to beta-ketoacyl-acyl carrier protein/coenzyme
      A reductase and belongs to the superfamily of short-chain alcohol dehydrogenase.
      The function of the BarS1 protein in VB biosynthesis was confirmed by BarS1
      dependent in vitro conversion of 6-dehydro-VB-A to VB-A, the last catalytic step
      in VB biosynthesis. Of the four possible enantiomeric products from racemic 6
      dehydro-VB-A as a substrate, only the natural enantiomer of (2R,3R,6S)-VB-A was
      produced by the purified recombinant BarS1 (rBarS1), indicating that rBarS1 is
      the stereospecific reductase recognizing (3R)-isomer as a substrate and reducing
      it stereospecifically to the (6S) product. In the DeltabarS1 mutant created by
      homologous recombination, the production of VB as well as the production of
      virginiamycin was lost. The production of virginiamycin by the DeltabarS1 mutant
      was fully recovered by the external addition of VB to the culture, which
      indicates that the barS1 gene is essential in the biosynthesis of the
      autoregulator VBs in S. virginiae and that the failure of virginiamycin
      production was a result of the loss of VB production.

PMID- 12193630
TI  - Regulatory circuitry of the CsrA/CsrB and BarA/UvrY systems of Escherichia coli.
AB  - The global regulator CsrA (carbon storage regulator) is an RNA binding protein
      that coordinates central carbon metabolism, activates flagellum biosynthesis and
      motility, and represses biofilm formation in Escherichia coli. CsrA activity is
      antagonized by the untranslated RNA CsrB, to which it binds and forms a globular
      ribonucleoprotein complex. CsrA indirectly activates csrB transcription, in an
      apparent autoregulatory mechanism. In the present study, we elucidate the
      intermediate regulatory circuitry of this system. Mutations affecting the
      BarA/UvrY two-component signal transduction system decreased csrB transcription
      but did not affect csrA'-'lacZ expression. The uvrY defect was severalfold more
      severe than that of barA. Both csrA and uvrY were required for optimal barA
      expression. The latter observation suggests an autoregulatory loop for UvrY.
      Ectopic expression of uvrY suppressed the csrB-lacZ expression defects caused by
      uvrY, csrA, or barA mutations; csrA suppressed csrA or barA defects; and barA
      complemented only the barA mutation. Purified UvrY protein stimulated csrB-lacZ
      expression approximately sixfold in S-30 transcription-translation reactions,
      revealing a direct effect of UvrY on csrB transcription. Disruption of sdiA,
      which encodes a LuxR homologue, decreased the expression of uvrY'-'lacZ and csrB
      lacZ fusions but did not affect csrA'-'lacZ. The BarA/UvrY system activated
      biofilm formation. Ectopic expression of uvrY stimulated biofilm formation by a
      csrB-null mutant, indicative of a CsrB-independent role for UvrY in biofilm
      development. Collectively, these results demonstrate that uvrY resides downstream
      from csrA in a signaling pathway for csrB and that CsrA stimulates UvrY-dependent
      activation of csrB expression by BarA-dependent and -independent mechanisms.

PMID- 12193633
TI  - R391: a conjugative integrating mosaic comprised of phage, plasmid, and
      transposon elements.
AB  - The conjugative, chromosomally integrating element R391 is the archetype of the
      IncJ class of mobile genetic elements. Originally found in a South African
      Providencia rettgeri strain, R391 carries antibiotic and mercury resistance
      traits, as well as genes involved in mutagenic DNA repair. While initially
      described as a plasmid, R391 has subsequently been shown to be integrated into
      the bacterial chromosome, employing a phage-like integration mechanism closely
      related to that of the SXT element from Vibrio cholerae O139. Analysis of the
      complete 89-kb nucleotide sequence of R391 has revealed a mosaic structure
      consisting of elements originating in bacteriophages and plasmids and of
      transposable elements. A total of 96 open reading frames were identified; of
      these, 30 could not be assigned a function. Sequence similarity suggests a
      relationship of large sections of R391 to sequences from Salmonella, in
      particular those corresponding to the putative conjugative transfer proteins,
      which are related to the IncHI1 plasmid R27. A composite transposon carrying the
      kanamycin resistance gene and a novel insertion element were identified.
      Challenging the previous assumption that IncJ elements are plasmids, no plasmid
      replicon was identified on R391, suggesting that they cannot replicate
      autonomously.

PMID- 12193634
TI  - ExbB and ExbD do not function independently in TonB-dependent energy
      transduction.
AB  - ExbB and ExbD proteins are part of the TonB-dependent energy transduction system
      and are encoded by the exb operon in Escherichia coli. TonB, the energy
      transducer, appears to go through a cycle during energy transduction, with the
      absence of both ExbB and ExbD creating blocks at two points: (i) in the inability
      of TonB to respond to the cytoplasmic membrane proton motive force and (ii) in
      the conversion of TonB from a high-affinity outer membrane association to a high
      affinity cytoplasmic membrane association. The recent observation that ExbB
      exists in 3.5-fold molar excess relative to the molarity of ExbD in E. coli
      suggests the possibility of two types of complexes, those containing both ExbB
      and ExbD and those containing only ExbB. Such distinct complexes might
      individually manifest one of the two activities described above. In the present
      study this hypothesis was tested and rejected. Specifically, both ExbB and ExbD
      were found to be required for TonB to conformationally respond to proton motive
      force. Both ExbB and ExbD were also required for association of TonB with the
      cytoplasmic membrane. Together, these results support an alternative model where
      all of the ExbB in the cell occurs in complex with all of the ExbD in the cell.
      Based on recently determined cellular ratios of TonB system proteins, these
      results suggest the existence of a cytoplasmic membrane complex that may be as
      large as 520 kDa.

PMID- 12193635
TI  - Insufficient expression of the ilv-leu operon encoding enzymes of branched-chain
      amino acid biosynthesis limits growth of a Bacillus subtilis ccpA mutant.
AB  - Bacillus subtilis ccpA mutant strains exhibit two distinct phenotypes: they are
      defective in catabolite repression, and their growth on minimal media is strongly
      impaired. This growth defect is largely due to a lack of expression of the gltAB
      operon. However, growth is impaired even in the presence of glutamate. Here, we
      demonstrate that the ccpA mutant strain needs methionine and the branched-chain
      amino acids for optimal growth. The control of expression of the ilv-leu operon
      by CcpA provides a novel regulatory link between carbon and amino acid
      metabolism.

PMID- 12193636
TI  - Global expression profile of Bacillus subtilis grown in the presence of sulfate
      or methionine.
AB  - DNA arrays were used to investigate the global transcriptional profile of
      Bacillus subtilis grown in the presence of sulfate or methionine as the sole
      sulfur source. The expression of at least 56 genes differed significantly under
      the two growth conditions. The expression of several genes belonging to the S-box
      regulon was repressed in the presence of methionine probably in response to S
      adenosylmethionine availability. The expression of genes encoding transporters
      (yhcL, ytmJKLMN, and yxeMO) was high when the sulfur source was methionine or
      taurine and reduced when it was sulfate.

PMID- 12193637
TI  - Amplification of the tetracycline resistance determinant of pAMalpha1 in
      Enterococcus faecalis requires a site-specific recombination event involving
      relaxase.
AB  - The small multicopy plasmid pAMalpha1 (9.75 kb) encoding tetracycline resistance
      in Enterococcus faecalis is known to generate tandem repeats of a 4.1-kb segment
      carrying tet(L) when cells are grown extensively in the presence of tetracycline.
      Here we show that the initial (rate-limiting) step involves a site-specific
      recombination event involving plasmid-encoded relaxase activity acting at two
      recombination sequences (RS1 and RS2) that flank the tet determinant. We also
      present the complete nucleotide sequence of pAMalpha1.

PMID- 12193638
TI  - Staphylococcus aureus contains two low-molecular-mass phosphotyrosine protein
      phosphatases.
AB  - The analysis of the different amino acid sequences deduced from the complete
      genome sequence of the gram-positive bacterium Staphylococcus aureus suggested
      the presence of two eukaryotic-protein-like low-molecular-mass phosphotyrosine
      protein phosphatases, which are usually found in gram-negative bacteria. To check
      this prediction, the corresponding genes were cloned and overexpressed in an
      Escherichia coli system. Two distinct proteins with an apparent molecular mass of
      23 kDa each, PtpA and PtpB, were produced and then purified by affinity
      chromatography and assayed for enzymatic properties. As expected, they both
      exhibited phosphatase activity in vitro, with a maximum value at a pH of around
      6.2 and at a temperature of 40 degrees C. In addition, their kinetic constants,
      their specificity for phosphotyrosine residues, and their sensitivity to two
      phosphatase inhibitors, N-ethylmaleimide and orthovanadate, matched those of acid
      low-molecular-mass phosphotyrosine protein phosphatases.

PMID- 12193641
TI  - Development of one-dimensional band structure in artificial gold chains.
AB  - The ability of a scanning tunneling microscope to manipulate single atoms is used
      to build well-defined gold chains on NiAl(110). The electronic properties of the
      one-dimensional chains are dominated by an unoccupied electron band, gradually
      developing from a single atomic orbital present in a gold atom. Spatially
      resolved conductance measurements along a 20-atom chain provide the dispersion
      relation, effective mass, and density of states of the free electron-like band.
      These experiments demonstrate a strategy for probing the interrelation between
      geometric structure, elemental composition, and electronic properties in metallic
      nanostructures.

PMID- 12193640
TI  - Regulation of heterochromatic silencing and histone H3 lysine-9 methylation by
      RNAi.
AB  - Eukaryotic heterochromatin is characterized by a high density of repeats and
      transposons, as well as by modified histones, and influences both gene expression
      and chromosome segregation. In the fission yeast Schizosaccharomyces pombe, we
      deleted the argonaute, dicer, and RNA-dependent RNA polymerase gene homologs,
      which encode part of the machinery responsible for RNA interference (RNAi).
      Deletion results in the aberrant accumulation of complementary transcripts from
      centromeric heterochromatic repeats. This is accompanied by transcriptional de
      repression of transgenes integrated at the centromere, loss of histone H3 lysine
      9 methylation, and impairment of centromere function. We propose that double
      stranded RNA arising from centromeric repeats targets formation and maintenance
      of heterochromatin through RNAi.

PMID- 12193639
TI  - Interactions between integrase and excisionase in the phage lambda excisive
      nucleoprotein complex.
AB  - Bacteriophage lambda site-specific recombination comprises two overall reactions,
      integration into and excision from the host chromosome. Lambda integrase (Int)
      carries out both reactions. During excision, excisionase (Xis) helps Int to bind
      DNA and introduces a bend in the DNA that facilitates formation of the proper
      excisive nucleoprotein complex. The carboxyl-terminal alpha-helix of Xis is
      thought to interact with Int through direct protein-protein interactions. In this
      study, we used gel mobility shift assays to show that the amino-terminal domain
      of Int maintained cooperative interactions with Xis. This finding indicates that
      the amino-terminal arm-type DNA binding domain of Int interacts with Xis.

PMID- 12193642
TI  - Specification of jaw subdivisions by Dlx genes.
AB  - The success of vertebrates was due in part to the acquisition and modification of
      jaws. Jaws are principally derived from the branchial arches, embryonic
      structures that exhibit proximodistal polarity. To investigate the mechanisms
      that specify the identity of skeletal elements within the arches, we examined
      mice lacking expression of Dlx5 and Dlx6, linked homeobox genes expressed
      distally but not proximally within the arches. Dlx5/6-/- mutants exhibit a
      homeotic transformation of lower jaws to upper jaws. We suggest that nested Dlx
      expression in the arches patterns their proximodistal axes. Evolutionary
      acquisition and subsequent refinement of jaws may have been dependent on
      modification of Dlx expression.

PMID- 12193643
TI  - Molecular biology. RNAi and heterochromatin--a hushed-up affair.

PMID- 12193644
TI  - Small RNAs correspond to centromere heterochromatic repeats.

PMID- 12193645
TI  - Arrangement of RecA protein in its active filament determined by polarized-light
      spectroscopy.
AB  - Linear dichroism (LD) polarized-light spectroscopy is used to determine the
      arrangement of RecA in its large filamentous complex with DNA, active in
      homologous recombination. Angular orientation data for two tryptophan and seven
      tyrosine residues, deduced from differential LD of wild-type RecA vs. mutants
      that were engineered to attenuate the UV absorption of selected residues,
      revealed a rotation by some 40 degrees of the RecA subunits relative to the
      arrangement in crystal without DNA. In addition, conformational changes are
      observed for tyrosine residues assigned to be involved in DNA binding and in RecA
      RecA contacts, thus potentially related to the global structure of the filament
      and its biological function. The presented spectroscopic approach, called "Site
      Specific Linear Dichroism" (SSLD), may find forceful applications also to other
      biologically important fibrous complexes not amenable to x-ray crystallographic
      or NMR structural analysis.

PMID- 12193646
TI  - Structural genomics of the Thermotoga maritima proteome implemented in a high
      throughput structure determination pipeline.
AB  - Structural genomics is emerging as a principal approach to define protein
      structure-function relationships. To apply this approach on a genomic scale,
      novel methods and technologies must be developed to determine large numbers of
      structures. We describe the design and implementation of a high-throughput
      structural genomics pipeline and its application to the proteome of the
      thermophilic bacterium Thermotoga maritima. By using this pipeline, we
      successfully cloned and attempted expression of 1,376 of the predicted 1,877
      genes (73%) and have identified crystallization conditions for 432 proteins,
      comprising 23% of the T. maritima proteome. Representative structures from TM0423
      glycerol dehydrogenase and TM0449 thymidylate synthase-complementing protein are
      presented as examples of final outputs from the pipeline.

PMID- 12193647
TI  - Using mechanical force to probe the mechanism of pausing and arrest during
      continuous elongation by Escherichia coli RNA polymerase.
AB  - Escherichia coli RNA polymerase translocates along the DNA discontinuously during
      the elongation phase of transcription, spending proportionally more time at some
      template positions, known as pause and arrest sites, than at others. Current
      models of elongation suggest that the enzyme backtracks at these locations, but
      the dynamics are unresolved. Here, we study the role of lateral displacement in
      pausing and arrest by applying force to individually transcribing molecules. We
      find that an assisting mechanical force does not alter the translocation rate of
      the enzyme, but does reduce the efficiency of both pausing and arrest. Moreover,
      arrested molecules cannot be rescued by force, suggesting that arrest occurs by a
      bipartite mechanism: the enzyme backtracks along the DNA followed by a
      conformational change of the ternary complex (RNA polymerase, DNA and
      transcript), which cannot be reversed mechanically.

PMID- 12193648
TI  - Prospective isolation of human clonogenic common myeloid progenitors.
AB  - The hierarchical development from hematopoietic stem cells to mature cells of the
      hematolymphoid system involves progressive loss of self-renewal capacity,
      proliferation ability, and lineage potentials. Here we show the prospective
      isolation of early developmental intermediates, the human clonogenic common
      myeloid progenitors and their downstream progeny, the granulocyte/macrophage and
      megakaryocyte/erythrocyte progenitors. All three populations reside in the
      lineage-negative (lin(-)) CD34(+)CD38(+) fraction of adult bone marrow as well as
      in cord blood. They are distinguishable by the expression of the IL-3R alpha
      chain, the receptor of an early-acting hematopoietic cytokine, and CD45RA, an
      isoform of a phosphotyrosine phosphatase involved in negative regulation of
      cytokine signaling. Multipotent progenitors, early lymphoid progenitors, and the
      here-defined myeloid progenitors express distinct profiles of hematopoiesis
      affiliated genes. The isolation of highly purified hematopoietic intermediates
      provides tools to better understand developmental programs underlying normal and
      leukemic hematopoiesis.

PMID- 12193649
TI  - Direct evidence that sulfhydryl groups of Keap1 are the sensors regulating
      induction of phase 2 enzymes that protect against carcinogens and oxidants.
AB  - Coordinate induction of phase 2 proteins and elevation of glutathione protect
      cells against the toxic and carcinogenic effects of electrophiles and oxidants.
      All inducers react covalently with thiols at rates that are closely related to
      their potencies. Inducers disrupt the cytoplasmic complex between the actin-bound
      protein Keap1 and the transcription factor Nrf2, thereby releasing Nrf2 to
      migrate to the nucleus where it activates the antioxidant response element (ARE)
      of phase 2 genes and accelerates their transcription. We cloned, overexpressed,
      and purified murine Keap1 and demonstrated on native gels the formation of
      complexes of Keap1 with the Neh2 domain of Nrf2 and their concentration-dependent
      disruption by inducers such as sulforaphane and bis(2-hydroxybenzylidene)acetone.
      The kinetics, stoichiometry, and order of reactivities of the most reactive of
      the 25 cysteine thiol groups of Keap1 have been determined by tritium
      incorporation from [(3)H]dexamethasone mesylate (an inducer and irreversible
      modifier of thiols) and by UV spectroscopy with sulforaphane, 2,2'-dipyridyl
      disulfide and 4,4'-dipyridyl disulfide (titrants of thiol groups), and two
      closely related Michael reaction acceptors [bis(2- and 4
      hydroxybenzylidene)acetones] that differ 100-fold in inducer potency and the UV
      spectra of which are bleached by thiol addition. With large excesses of these
      reagents nearly all thiols of Keap1 react, but sequential reaction with three
      successive single equivalents (per cysteine residue) of dipyridyl disulfides
      revealed excellent agreement with pseudo-first order kinetics, rapid successive
      declines in reaction velocity, and the stoichiometric formation of two
      equivalents of thiopyridone per reacted cysteine. This finding suggests that
      reaction of cysteine thiols is followed by rapid formation of protein disulfide
      linkages. The most reactive residues of Keap1 (C(257), C(273), C(288), and
      C(297)) were identified by mapping the dexamethasone-modified cysteines by mass
      spectrometry of tryptic peptides. These residues are located in the intervening
      region between BTB and Kelch repeat domains of Keap1 and probably are the direct
      sensors of inducers of the phase 2 system.

PMID- 12193650
TI  - Sleep forms memory for finger skills.
AB  - Practicing a motor skill triggers a process of memory consolidation that
      continues for hours after practice has ended, and becomes manifest in an improved
      skill at later testing. We used a sequential motor task (finger-to-thumb
      opposition task) to show that, in humans, the formation of motor skill memories
      essentially benefits from sleep. Independent of whether placed during daytime or
      nighttime, sleep after practice enhanced speed of sequence performance on average
      by 33.5% and reduced error rate by 30.1% as compared with corresponding intervals
      of wakefulness. The effect of sleep after learning proved to be stable when
      retesting was postponed for another night, to exclude effects of sleep loss and
      to assure that all subjects had sufficient sleep before retrieval testing. Also,
      the consolidating effect of sleep was specific for the motor sequence learned. It
      did not generalize to a similar sequence containing identical movement segments
      in a different order. Retention periods of wakefulness improved performance only
      moderately and only if placed during daytime. The observations demonstrate a
      critical role of sleep for storing and optimizing motor skills.

PMID- 12193651
TI  - Identification of macrophage liver X receptors as inhibitors of atherosclerosis.
AB  - Recent studies have identified the liver X receptors (LXR alpha and LXR beta) as
      important regulators of cholesterol metabolism and transport. LXRs control
      transcription of genes critical to a range of biological functions including
      regulation of high density lipoprotein cholesterol metabolism, hepatic
      cholesterol catabolism, and intestinal sterol absorption. Although LXR activity
      has been proposed to be critical for physiologic lipid metabolism and transport,
      direct evidence linking LXR signaling pathways to the pathogenesis of
      cardiovascular disease has yet to be established. In this study bone marrow
      transplantations were used to selectively eliminate macrophage LXR expression in
      the context of murine models of atherosclerosis. Our results demonstrate that
      LXRs are endogenous inhibitors of atherogenesis. Additionally, elimination of LXR
      activity in bone marrow-derived cells mimics many aspects of Tangier disease, a
      human high density lipoprotein deficiency, including aberrant regulation of
      cholesterol transporter expression, lipid accumulation in macrophages,
      splenomegaly, and increased atherosclerosis. These results identify LXRs as
      targets for intervention in cardiovascular disease.

PMID- 12193652
TI  - A duplicated copy of DMRT1 in the sex-determining region of the Y chromosome of
      the medaka, Oryzias latipes.
AB  - The genes that determine the development of the male or female sex are known in
      Caenorhabditis elegans, Drosophila, and most mammals. In many other organisms the
      existence of sex-determining factors has been shown by genetic evidence but the
      genes are unknown. We have found that in the fish medaka the Y chromosome
      specific region spans only about 280 kb. It contains a duplicated copy of the
      autosomal DMRT1 gene, named DMRT1Y. This is the only functional gene in this
      chromosome segment and maps precisely to the male sex-determining locus. The gene
      is expressed during male embryonic and larval development and in the Sertoli
      cells of the adult testes. These features make DMRT1Y a candidate for the medaka
      male sex-determining gene.

PMID- 12193653
TI  - 1-Cys peroxiredoxin overexpression protects cells against phospholipid
      peroxidation-mediated membrane damage.
AB  - 1-Cys peroxiredoxin (1-cysPrx) is a novel antioxidant enzyme able to reduce
      phospholipid hydroperoxides in vitro by using glutathione as a reductant. This
      enzyme is widely expressed and is enriched in lungs. A fusion protein of green
      fluorescent protein with 1-cysPrx was stably expressed in a lung-derived cell
      line (NCI-H441) lacking endogenous enzyme. Overexpressing cells (C17 or C48)
      degraded H(2)O(2) and t-butylhydroperoxide more rapidly and showed decreased
      sensitivity to oxidant stress as measured by (51)Cr release. On exposure to (*)OH
      generated by Cu(2+)-ascorbate (Asc), overexpressing cells compared with H441
      showed less increase in thiobarbituric acid-reactive substance and
      phosphatidylcholine hydroperoxide content. This effect was reversed by depletion
      of cellular glutathione. Diphenyl-1-pyrenoylphosphonium fluorescence, used as a
      real-time probe of membrane phospholipid peroxidation, increased immediately on
      exposure to Cu(2+)-Asc and was abolished by preincubation of cells with Trolox (a
      soluble vitamin E) or Tempol (a radical scavenger). The rate of diphenyl-1
      pyrenoylphosphonium fluorescence increase with Cu(2+)-Asc exposure was markedly
      attenuated in C17 and C48 cells as compared with H441. Annexin V-Cy3 was used to
      detect phosphatidylserine translocation from the inner to outer leaflet of the
      plasma membrane. Cu(2+)-Asc treatment induced phosphatidylserine translocation
      within 2 h in H441 cells but none was observed in C48 cells up to 24 h. These
      results indicate that 1-cysPrx can scavenge peroxides but in addition can reduce
      peroxidized membrane phospholipids. Thus, the enzyme can protect cells against
      oxidant-induced plasma membrane damage, thereby playing an important role in
      cellular defense against oxidant stress.

PMID- 12193654
TI  - A linear lattice model for polyglutamine in CAG-expansion diseases.
AB  - Huntington's disease and several other neurological diseases are caused by
      expanded polyglutamine [poly(Gln)] tracts in different proteins. Mechanisms for
      expanded (>36 Gln residues) poly(Gln) toxicity include the formation of
      aggregates that recruit and sequester essential cellular proteins [Preisinger,
      E., Jordan, B. M., Kazantsev, A. & Housman, D. (1999) Phil. Trans. R. Soc. London
      B 354, 1029-1034; Chen, S., Berthelier, V., Yang, W. & Wetzel, R. (2001) J. Mol.
      Biol. 311, 173-182] and functional alterations, such as improper interactions
      with other proteins [Cummings, C. J. & Zoghbi, H. Y. (2000) Hum. Mol. Genet. 9,
      909-916]. Expansion above the "pathologic threshold" ( approximately 36 Gln) has
      been proposed to induce a conformational transition in poly(Gln) tracts, which
      has been suggested as a target for therapeutic intervention. Here we show that
      structural analyses of soluble huntingtin exon 1 fusion proteins with 16 to 46
      glutamine residues reveal extended structures with random coil characteristics
      and no evidence for a global conformational change above 36 glutamines. An
      antibody (MW1) Fab fragment, which recognizes full-length huntingtin in mouse
      brain sections, binds specifically to exon 1 constructs containing normal and
      expanded poly(Gln) tracts, with affinity and stoichiometry that increase with
      poly(Gln) length. These data support a "linear lattice" model for poly(Gln), in
      which expanded poly(Gln) tracts have an increased number of ligand-binding sites
      as compared with normal poly(Gln). The linear lattice model provides a rationale
      for pathogenicity of expanded poly(Gln) tracts and a structural framework for
      drug design.

PMID- 12193655
TI  - Telomerase contributes to tumorigenesis by a telomere length-independent
      mechanism.
AB  - Once immortalized, human cells are susceptible to transformation by introduction
      of an oncogene such as ras. Several lines of evidence now suggest that the
      maintenance of telomere length is a major determinant of replicative lifespan in
      human cells and thus of the immortalized state. The majority of human tumor cells
      acquire immortality through expression of the catalytic subunit of telomerase
      (hTERT), whereas others activate an alternative mechanism of telomere maintenance
      (ALT) that does not depend on the actions of telomerase. We have examined whether
      ALT could substitute for telomerase in the processes of transformation in vitro
      and tumorigenesis in vivo. Expression of oncogenic H-Ras in the immortal ALT cell
      line GM847 did not result in their transformation. However, subsequent ectopic
      expression of hTERT in these cells imparted a tumorigenic phenotype. Indeed, this
      outcome was also observed after introduction of a mutant hTERT that retained
      catalytic activity but was incapable of maintaining telomere length. These
      studies indicate that hTERT confers an additional function that is required for
      tumorigenesis but does not depend on its ability to maintain telomeres.

PMID- 12193656
TI  - Sterols block binding of COPII proteins to SCAP, thereby controlling SCAP sorting
      in ER.
AB  - Sterols inhibit their own synthesis in mammalian cells by blocking the vesicular
      endoplasmic reticulum-to-Golgi transport of sterol regulatory element-binding
      protein (SREBP) cleavage-activating protein (SCAP), a sterol-sensing protein that
      escorts SREBPs. Unable to reach the Golgi, SREBPs are not processed by Golgi
      resident proteases, and they fail to activate genes required for cholesterol
      synthesis. The current studies were designed to reveal whether sterols block SCAP
      movement by inhibiting synthesis of special vesicles dedicated to SCAP, or
      whether sterols block SCAP incorporation into common coat protein (COP)II-coated
      vesicles. Through immunoisolation, we show that SCAP-containing vesicles, formed
      in vitro, also contain vesicular stomatitis virus glycoprotein (VSVG) protein, a
      classic marker of COPII-coated vesicles. Sterols selectively block incorporation
      of SCAP into these vesicles without blocking incorporation of VSVG protein. We
      show that the mammalian vesicular budding reaction can be reconstituted by
      recombinant yeast COPII proteins that support incorporation of SCAP as well as
      VSVG into vesicles. Sterols block SCAP incorporation into vesicles by blocking
      Sar1-dependent binding of the COPII proteins Sec 23/24 to SCAP. These studies
      demonstrate feedback control of a biosynthetic pathway by the regulated binding
      of COPII proteins to an endoplasmic reticulum-to-Golgi transport protein.

PMID- 12193657
TI  - Circadian genes in a blind subterranean mammal II: conservation and uniqueness of
      the three Period homologs in the blind subterranean mole rat, Spalax ehrenbergi
      superspecies.
AB  - We demonstrated that a subterranean, visually blind mammal has a functional set
      of three Per genes that are important components of the circadian clockwork in
      mammals. The mole rat superspecies Spalax ehrenbergi is a blind subterranean
      animal that lives its entire life underground in darkness. It has degenerated
      eyes, but the retina and highly hypertrophic harderian gland are involved in
      photoperiodic perception. All three Per genes oscillate with a periodicity of 24
      h in the suprachiasmatic nuclei, eye, and harderian gland and are expressed in
      peripheral organs. This oscillation is maintained under constant conditions. The
      light inducibility of sPer1 and sPer2, which are similar in structure to those of
      other mammals, indicates the role of these genes in clock resetting. However,
      sPer3 is unique in mammals and has two truncated isoforms, and its expressional
      analysis leaves its function unresolved. Per's expression analysis in the
      harderian gland suggests an important participation of this organ in the
      stabilization and resetting mechanism of the central pacemaker in the
      suprachiasmatic nuclei and in unique adaptation to life underground.

PMID- 12193658
TI  - Histone H3 lysine 4 methylation is mediated by Set1 and promotes maintenance of
      active chromatin states in fission yeast.
AB  - Methylation of histone H3 at lysine 4 (H3 Lys-4) or lysine 9 (H3 Lys-9) is known
      to define active and silent chromosomal domains respectively from fission yeast
      to humans. However, in budding yeast, H3 Lys-4 methylation is also necessary for
      silent chromatin assembly at telomeres and ribosomal DNA. Here we demonstrate
      that deletion of set1, which encodes a protein containing an RNA recognition
      motif at its amino terminus and a SET domain at the carboxy terminus, abolishes
      H3 Lys-4 methylation in fission yeast. Unlike in budding yeast, Set1-mediated H3
      Lys-4 methylation is not required for heterochromatin assembly at the silent
      mating-type region and centromeres in fission yeast. Our analysis suggests that
      H3 Lys-4 methylation is a stable histone modification present throughout the cell
      cycle, including mitosis. The loss of H3 Lys-4 methylation in set1Delta cells is
      correlated with a decrease in histone H3 acetylation levels, suggesting a
      mechanistic link between H3 Lys-4 methylation and acetylation of the H3 tail. We
      suggest that methylation of H3 Lys-4 primarily acts in the maintenance of
      transcriptionally poised euchromatic domains, and that this modification is
      dispensable for heterochromatin formation in fission yeast, which instead
      utilizes H3 Lys-9 methylation.

PMID- 12193660
TI  - Answers to missing mtDNA found at last.

PMID- 12193659
TI  - Cooperative activities of hematopoietic regulators recruit RNA polymerase II to a
      tissue-specific chromatin domain.
AB  - The hematopoietic transcription factor GATA-1 regulates erythropoiesis and beta
      globin expression. Although consensus GATA-1 binding sites exist throughout the
      murine beta-globin locus, we found that GATA-1 discriminates among these sites in
      vivo. Conditional expression of GATA-1 in GATA-1-null cells recapitulated the
      occupancy pattern. GATA-1 induced RNA polymerase II (pol II) recruitment to
      subregions of the locus control region and to the beta-globin promoters. The
      hematopoietic factor NF-E2 cooperated with GATA-1 to recruit pol II to the
      promoters. We propose that only when GATA-1 attracts pol II to the locus control
      region can pol II access the promoter in a NF-E2-dependent manner.

PMID- 12193661
TI  - Transdifferentiation of neural stem cells, or not?

PMID- 12193662
TI  - Angiotensin signaling and apoptosis in the neonatal heart: necessary evils?

PMID- 12193663
TI  - Angiotensin converting enzyme inhibition decreases cell turnover in the neonatal
      rat heart.
AB  - The renin angiotensin system plays an important role in growth and development.
      Exposure of the neonate to an ACE inhibitor increases mortality and results in
      growth retardation and abnormal development. We have demonstrated that ACE
      inhibition in the developing kidney increases apoptosis and decreases cell
      proliferation, which may account for renal growth impairment. To evaluate the
      role of endogenous angiotensin in cardiac development, the relationship between
      ACE inhibition, cell proliferation, apoptosis, several modulators of apoptosis
      (bcl-2, bcl-xl, and clusterin) was examined in the developing rat heart. Thirty
      five newborn rat pups were treated with enalapril (30 mg/kg/d) or a vehicle
      (control group) for 7 d, and hearts were removed for rt-PCR and Western blotting
      of bcl-2, bcl-xl, and clusterin. An additional 10 rat pups were treated with
      hydralazine (10 mg/kg/d) or a vehicle, to serve as a hypotensive control. Cell
      proliferation was determined by PCNA immunostaining, and apoptosis was detected
      using the total TUNEL technique. Enalapril treatment resulted in a 24% mortality,
      reduced body weight, and decreased heart weight (p < 0.05). Enalapril decreased
      proliferating myocytes by 23%, and reduced proliferating cardiac interstitial
      cells by 8.1% (p < 0.05). Enalapril also decreased myocytes apoptosis by 60%, but
      the proportion of myocytes undergoing apoptosis was 10-fold less than that of
      proliferating cells. Cardiac bcl-2 mRNA, clusterin mRNA, bcl-2 protein, and bcl
      xl protein content were not changed, but clusterin protein expression was
      decreased by enalapril treatment. Hydralazine did not alter cardiac cell
      proliferation or apoptosis. We conclude that ACE inhibition decreases cell
      turnover in the developing rat heart, which may contribute to cardiac growth
      impairment. The loss of myocytes may lead to greater myocyte hypertrophy and
      myocardial damage during later life.

PMID- 12193664
TI  - Differential responses to systemic and local angiotensin II infusions in
      conscious postnatal sheep.
AB  - Angiotensin II (ANG II) increases blood pressure (MAP) via specific ANG II
      receptors (AT) and is considered important in regulating MAP after birth. In
      adult animals, AT(1) receptors predominate in vascular smooth muscle (VSM) and
      mediate vasoconstriction. In newborn sheep, AT(2) receptors, which do not mediate
      vasoconstriction, predominate in vascular smooth muscle until 2 wk postnatal when
      they are replaced by AT(1). Thus, the mechanisms whereby ANG II increases MAP
      after birth are unclear. We examined the effects of ANG II on femoral vascular
      resistance (FmVR) and blood flow (FmBF) in serial studies of newborn sheep (n =
      7) at 7-14 d, 15-21 d, and 22-35 d. Animals had femoral catheters implanted for
      systemic ANG II infusions and cardiovascular monitoring, and a flow probe was
      implanted on the contralateral artery proximal to the superficial saphenous
      artery, which contained a catheter for intra-arterial ANG II infusions. Studies
      were performed using a range of systemic and intra-arterial ANG II doses.
      Systemic ANG II increased MAP dose-dependently at all ages (p < 0.001); however,
      responses were not age dependent. FmBF rose dose dependently at 7-14 d (p <
      0.001) and was unchanged at older ages. FmVR was unaffected at 7-14 d, but values
      increased dose dependently at 15-21 d and 22-3 5d (p < 0.001), although never
      exceeded relative increases in MAP. Local ANG II did not alter MAP, FmBF, or FmVR
      at any age. Although systemic ANG II increases MAP and FmVR dose dependently
      after birth, ANG II-induced vasoconstriction is attenuated. Furthermore, intra
      arterial ANG II does not alter FmVR in the absence of systemic responses,
      suggesting incomplete vascular smooth muscle AT(1) expression, stimulation of
      local ANG II antagonists, or ANG II-mediated release of another vasoconstrictor.

PMID- 12193665
TI  - COX-1 and COX-2 contributions to basal and IL-1 beta-stimulated prostanoid
      synthesis in human neonatal cerebral microvascular endothelial cells.
AB  - Mechanisms of endothelium-dependent regulation of cerebral circulation in human
      neonates are poorly understood owing to the lack of experimental data.
      Prostanoids, the products of the cyclooxygenase (COX) pathway, appear to be
      important regulators of blood flow in neonates. COX activity in cultured
      endothelial cells from small (60-300 microm) and large (>300 microm) microvessels
      from the autopsy specimens of neonatal human cerebral cortex and cerebellum (22
      26 wk gestational age) was detected as production of vasodilator prostanoids,
      prostacyclin [as 6-keto-prostaglandin (PG) F(1 alpha)] and PGE(2) from
      arachidonic acid. Treatment of neonatal human cerebral microvascular endothelial
      cells (hCMVEC) with IL-1 beta (50 ng/mL, 17 h) stimulated COX activity 5- to 20
      fold. Basal and IL-1 beta-stimulated COX activities were inhibited by NS-398,
      indicating substantial COX-2 contribution to endothelial prostanoid synthesis in
      neonatal human brain cortex and cerebellum at rest and when mimicking the
      inflammatory conditions. Increased COX-2-linked activity in response to IL-1 beta
      was observed in hCMVEC from both cerebrum and cerebellum (5- to 20-fold), while
      under the same conditions elevated COX-1-linked activity was detected only in
      hCMVEC from cerebellum (5- to 10-fold). In IL-1 beta-treated hCMVEC, a shift
      toward PGE(2) as the major vasodilator product of the COX pathway was observed.
      Acute treatment with the protein tyrosine kinase inhibitor, tyrphostin 25,
      inhibited basal and IL-1 beta-induced COX activities, suggesting the importance
      of posttranslational modifications in endothelial COX-2 activation in human
      brain. Altogether, these data indicate that both COX-1 and COX-2 contribute to
      endothelial prostanoid synthesis in the neonatal human brain under basal
      conditions and in response to proinflammatory cytokine IL-1 beta.

PMID- 12193666
TI  - The number of podocyte slit diaphragms is decreased in minimal change nephrotic
      syndrome.
AB  - The pathophysiology of proteinuria in acquired kidney diseases is mostly unknown.
      Recent findings in genetic renal diseases suggest that glomerular epithelial
      cells (podocytes) and the slit diaphragm connecting the podocyte foot processes
      play an important role in the development of proteinuria. In this work we
      systematically evaluated the podocyte slit pores by transmission electron
      microscopy in two important nephrotic diseases, minimal change nephrotic syndrome
      (MCNS) and membranous nephropathy (MN). As controls, we used kidneys with
      tubulointerstitial nephritis (TIN). Effacement of podocyte foot processes was
      evident in proteinuric kidneys. However, quite normal looking foot processes and
      slit pores with varying width were also observed. Careful analysis of slit pores
      revealed, that the proportion of the pores spanned by the linear image of slit
      diaphragm, was reduced by 39% in kidneys from MCNS patients (1265 pores analyzed)
      compared with TIN samples (902 pores analyzed, p = 0.0003). To enhance the
      detection rate of the slit diaphragms, the "empty" podocyte pores were further
      analyzed with tilting series from -45 to +45. This revealed the linear diaphragm
      image in 71% and 26% of the slits in TIN and MCNS kidneys, respectively (p =
      0.0003). In contrast to findings in MCNS, no significant reduction of the slit
      diaphragms were seen in MN kidneys compared with the controls. The results
      suggest that MCNS is associated with disruption of glomerular slit diaphragms.

PMID- 12193667
TI  - Postnatal lung inflammation increased by ventilation of preterm lambs exposed
      antenatally to Escherichia coli endotoxin.
AB  - Chorioamnionitis resulting in exposure of the fetal lung to inflammation is
      frequent before preterm delivery. The initiation of mechanical ventilation in the
      preterm recruits granulocytes to the lungs and increases proinflammatory cytokine
      expression in the lungs. We hypothesized that when the prematurely born newborn
      with chorioamnionitis was ventilated, inflammation would increase. Therefore, we
      asked whether inflammatory exposure to the fetal lung caused by intra-amniotic
      endotoxin (10 mg, Escherichia coli 055:beta 5) given at 100 d gestation would
      alter the inflammatory responses to the mechanical ventilation in surfactant
      treated preterm lambs delivered at 130 d gestation. Cells in alveolar washes,
      proinflammatory cytokine expression, and surfactant protein mRNA expression were
      not different for saline and endotoxin exposed lambs that were not ventilated.
      The endotoxin- and saline-exposed control animals had similar lung function for 6
      h of ventilation. Bronchoalveolar lavage fluid from the ventilated and antenatal
      endotoxin-exposed animals contained 5.7 times more monocytes, 12 times more
      lymphocytes, and a nonsignificant increase in neutrophils. Cells from the
      bronchoalveolar lavage fluid expressed 3-fold more IL-6 and IL-8 mRNA than did
      cells from the saline exposed comparison animals. An antenatal exposure of the
      fetal lung to endotoxin enhanced the subsequent inflammatory response of the
      ventilated preterm lung.

PMID- 12193668
TI  - Natural reinfection with respiratory syncytial virus does not boost virus
      specific T-cell immunity.
AB  - To determine the role of respiratory syncytial virus (RSV)-specific cell-mediated
      immunity during natural reinfection, we investigated whether RSV-specific T-cell
      responses protect against reinfection and, subsequently, whether reinfection
      boosts virus-specific memory. In a cohort of 55 infants who were hospitalized for
      RSV bronchiolitis, RSV-specific lymphoproliferative responses in the peripheral
      blood were measured at three time-points: on admission, 4 wk after admission, and
      1 y later, after the second winter season. Memory was defined as a stimulation
      index (SI) >2. During the second winter season, nasal secretions were collected
      in every case of a runny nose. Reinfection was diagnosed if immunofluorescence or
      PCR was positive for RSV. Virus-specific memory was found in one child on
      admission for primary RSV infection, whereas 4 wk later 44 infants (80%) had
      memory. Reinfection with RSV was found in 23 infants (43%) during the second
      winter season. After the second season, memory was found in 20 infants (38%). No
      differences in SI after the second winter season were found between infants with
      and without reinfection (2.3 versus 2.1). However, a highly significant
      correlation was found between SI measured 4 wk after primary RSV infection and SI
      after the second winter season (r = 0.40, p = 0.001). In conclusion, RSV-specific
      T-cell responses did not provide protection against reinfection. Moreover,
      reinfection did not boost RSV-specific T-cell proliferation. To explain both
      findings, it is hypothesized that RSV-specific T cells fail to expand in vivo
      upon reinfection.

PMID- 12193669
TI  - Steroids fail to down-regulate respiratory syncytial virus-induced IL-8 secretion
      in infants.
AB  - In the first year of life, respiratory syncytial virus (RSV) is the major cause
      of bronchiolitis and is characterized by extensive inflammatory cell influx to
      airways. We investigated whether this might reflect a failure to down-regulate
      secretion of the chemokine IL-8, which has been identified as a key
      chemoattractant during host defense to RSV. Two milliliters of blood were
      obtained from infants, children aged 1-12 y, and adults. Peripheral blood
      mononuclear cells (PBMC) were isolated and infected with RSV, and IL-8 secretion
      was measured by ELISA. The effect of preincubation of PBMC with either 0.1-10
      micro M dexamethasone or 1-100 ng/mL of one of the down-regulatory T helper 2
      cytokines IL-4, IL-10, or IL-13 before RSV infection was examined. RSV stimulated
      IL-8 secretion in a dose-dependent manner similarly in all age groups. IL-8
      secretion occurred mainly within 24 h of infection, with maximal concentrations
      of 30,000-46,000 pg/10(6) cells. IL-4 caused modest inhibition and IL-10 and IL
      13 caused no inhibition of IL-8 secretion in all groups. Dexamethasone inhibited
      IL-8 secretion by 34 +/- 8% in children and by 41 +/- 3% in adults but had no
      effect on infant PBMC. In summary, RSV-induced IL-8 secretion from infant PBMC is
      equal to that in children and adults and relatively unaffected by down-regulatory
      cytokines. However, the inhibitory effects of steroids on IL-8 secretion are
      absent in infants, which may partly explain why they develop more severe
      bronchiolitis, and why steroid therapy is unsuccessful in clinical practice.

PMID- 12193670
TI  - Association between the Asp299Gly polymorphisms in the Toll-like receptor 4 and
      premature births in the Finnish population.
AB  - Premature birth causes significant health risks of the neonate and increases the
      cost for neonatal care. Urogenital infection, often caused by Gram-negative
      bacteria, is a known risk factor. Toll-like receptor-4 (TLR4) is the major
      endotoxin-signaling receptor and as such is crucial for the initiation of the
      innate immune response against Gram-negative bacteria. Recently, a variant in the
      human TLR4 gene was shown to be associated with impaired receptor function and an
      increased likelihood of Gram-negative sepsis. In the present study, we determined
      whether the same polymorphism in TLR4 gene is associated with an increased risk
      for premature birth. We analyzed genotypes for a Finnish study population
      consisting of a total of 351 term infants and 440 premature infants (gestational
      age <35 wk; 282 singletons, 158 multiples) and 94 mothers for the presence of the
      TLR4 polymorphisms Asp299Gly and Thr399Ile. These polymorphisms were in linkage
      disequilibrium. The 299Gly allele frequencies were 10.6% (93 of 880) in premature
      infants and 8.3% (58 of 72) in term infants. Excluding multiple pregnancies that
      often result in premature births, 23.8% (67 of 282) of premature infants and
      24.2% (15 of 62) of the mothers of premature infants compared with 15.9% (55 of
      345) of term infants and 15.0% (3 of 20) of the mothers delivering at term were
      carriers of the TLR4 variant. The frequencies of 299Gly allele and Asp/Gly or
      Gly/Gly genotype carrier status in premature singleton infants were higher than
      in term singleton infants (p = 0.024, p = 0.028, respectively) or in premature
      multiples (p = 0.036, p = 0.044, respectively). According to the present results
      an allelic variation in the TLR4 receptor was associated with increased risk of
      premature birth.

PMID- 12193671
TI  - Telomere length in the newborn.
AB  - Telomere length is similar in different organs of the human fetus but variable
      among fetuses. During extrauterine life telomere length is highly variable among
      individuals and longer in women than men. In the present work we addressed the
      following questions: 1) Are there sex-related differences in telomere length at
      birth? 2) Is there synchrony (i.e. correlation in length) of telomeres in tissues
      within the newborn? 3) Is the variability in telomere length among newborns as
      large as that in adults? We studied normal male and female newborns who donated
      DNA samples from three sources: white blood cells, umbilical artery, and
      foreskin. Telomere length was measured by the mean length of the terminal
      restriction fragments (TRF). TRF length was not different between male and female
      newborns. It was highly synchronized among the DNA samples from white blood
      cells, umbilical artery and skin within individual donors but exhibited a high
      variability among donors. We conclude that there is no evidence for the effect of
      sex on telomere length at birth, suggesting that longer telomeres in women than
      men arise from a slower rate of telomeric attrition in women. The variability in
      telomere length among newborns and synchrony in telomere length within organs of
      the newborn are consistent with the concept that variations in telomere length
      among adults are in large part attributed to determinants (genetic and
      environmental) that start exerting their effect in utero.

PMID- 12193672
TI  - Chronic postbronchiolitis airway instability induced with anti-IFN-gamma antibody
      in F344 rats.
AB  - Analogous to childhood-onset asthma in humans, rats may develop a chronic
      asthmalike phenotype, depending on their genetic background and the age at which
      they experience a viral airway injury. Brown Norway rats develop a
      postbronchiolitis asthmalike phenotype that may be prevented with supplements of
      interferon-gamma (IFN-gamma); we hypothesized that the normally resistant F344
      rat strain would develop the asthmalike phenotype if the IFN-gamma response were
      suppressed during viral illness. Weanling F344 rats were pretreated with anti-IFN
      gamma or control antibody, and inoculated with Sendai virus or vehicle. Anti-IFN
      gamma treatment reduced lung IFN-gamma and increased IL-4 mRNA during the
      infection. Physiologic studies performed 8 wk later revealed premature airway
      closure (p = 0.03) and elevated specific pulmonary resistance (p < 0.01) in the
      postbronchiolitis anti-IFN-gamma group compared with noninfected controls and
      untreated postbronchiolitis rats. However, unlike the postbronchiolitis
      asthmalike phenotype in Brown Norway rats, bronchiolar inflammation and fibrosis
      were absent in the F344 rats. Lung elastic recoil and alveolar surface density
      also were unchanged compared with noninfected control rats. We conclude that
      there is an interactive effect of a weak IFN-gamma response and viral
      bronchiolitis at an early age that may result in persistent postbronchiolitis
      airway dysfunction. The presence of premature airway closure that is independent
      of airway wall inflammation or changes in lung elastic recoil suggests peripheral
      airway instability as a mechanism for the airway obstruction.

PMID- 12193673
TI  - Decreased indicators of lung injury with continuous positive expiratory pressure
      in preterm lambs.
AB  - Continuous positive airway pressure (CPAP) is being used clinically to avoid
      mechanical ventilation of preterm infants as a strategy to minimize lung injury.
      There is little experimental information about how CPAP might minimize lung
      injury after preterm birth. We induced preterm labor in antenatal glucocorticoid
      treated sheep carrying twins at 133 d gestation with an inhibitor of progesterone
      synthesis. The lambs delivered spontaneously approximately 2 d later and were
      randomized to three groups: no ventilation (n = 4), conventional mechanical
      ventilation to a target PCO(2) of 40 mm Hg (n = 5), or CPAP using a bubble CPAP
      device set to deliver 5 cm H(2)O pressure (n = 6). The CPAP lambs breathed
      without distress and maintained PCO(2) values of approximately 60 mm Hg. At 2 h
      of age, the lungs of the CPAP lambs held 74 +/- 4 mL/kg air at 40 cm H(2)O
      pressure, which was more than the 60 +/- 3 mL/kg for the ventilated lambs (p <
      0.05). Lymphocyte and monocyte numbers in alveolar washes were equivalent in the
      unventilated, ventilated, and CPAP lambs. However, no neutrophils were found in
      the unventilated lambs, and the ventilated lambs had 6.6 times more neutrophils
      in alveolar washes than did the CPAP lambs (p < 0.05). The cells in alveolar wash
      from CPAP lambs contained less hydrogen peroxide than did the cells from
      ventilated lambs (p < 0.05). In this model in preterm lambs CPAP results in lower
      indicators of acute lung injury than does mechanical ventilation during the first
      2 h of life.

PMID- 12193674
TI  - Evaluation of exhaled nitric oxide in schoolchildren at different exhalation flow
      rates.
AB  - Nitric oxide (NO) in exhaled air is believed to reflect allergic inflammation in
      the airways. Measured levels of exhaled NO vary with the exhaled flow rate, which
      therefore must be standardized. The aim of this study was to estimate the optimal
      exhalation flow rate when measuring NO in exhaled air. We studied 15 asthmatic
      children (8-18 y) with elevated NO levels and 15 age-matched controls and focused
      on how the quality of the NO curve profile, the discriminatory power, and the
      reproducibility were influenced by the exhalation flow rate. We used an on-line
      system for NO measurements at six different exhalation flow rates in the interval
      of 11-382 mL/s. The fraction of exhaled nitric oxide (FENO) was highly flow
      dependent as was expected. Intermediate flow rates yielded a flat and stable NO
      plateau and were considerably easier to interpret than those obtained at the
      highest and lowest flow rates. The ratio of FENO between asthmatics and controls
      was lower at higher flow rates and a considerable overlap in NO values was
      demonstrated at all flow rates except 50 mL/s. The reproducibility was much lower
      at more extreme flow rates and was best at 50 mL/s. We conclude that a target
      exhalation flow rate of approximately 50 mL/s is to be preferred using the single
      breath method for on-line NO measurements in schoolchildren.

PMID- 12193675
TI  - Quality of diet, body position, and time after feeding influence behavioral
      states in low birth weight infants.
AB  - The effects of variations in carbohydrate and fat intake and body position on
      behavioral activity states were evaluated in 64 healthy, growing low birth weight
      infants (birth weight, 750-1600 g). The infants, enrolled in a prospective,
      randomized, double-blind, controlled study of effects of quality of dietary
      energy, were fed one of the five formulas. These formulas contained fixed intakes
      of protein (4 g/kg per day) but different intakes of carbohydrate (9.1 to 20.4
      g/kg per day) and fat (4.3 to 9.5 g/kg per day). Six-hour daytime sleep studies
      were performed at 2-wk intervals from time of full enteral intake until discharge
      (mean postconceptional age at first study, 33.2 +/- 1.8 wk). Infants were
      randomly assigned to the prone or supine position for the first 3-h postprandial
      period; the position was reversed during the second 3 h. Behavioral activity
      state, i.e. quiet sleep (QS), active sleep, indeterminate sleep, awake, or crying
      was coded each minute throughout the postprandial period. The overall incidence
      of QS was almost double in the prone position versus the supine (p < 0.0001). In
      contrast, the probability of being in either of the two wakeful states (awake and
      crying) was increased when infants were placed in supine position (p < 0.0001).
      Increased likelihood of being in QS while prone was found only during the 30 min
      after and before feeding in a 150-min prandial cycle. In contrast, increased
      amounts of awake and crying in supine position were observed throughout the
      feeding interval. As carbohydrate intake increased, time spent in QS in supine
      position increased (from 8.6% to 12.5%, p < 0.02), and a trend in the same
      direction was noted for the prone position (p = 0.06). However, during
      postprandial minutes 10-100, when QS is likely to be entrained by the nutrient
      intake, enhancement of QS was found in the prone position only (p < 0.02).
      Carbohydrate intake influences the total time spent and the distribution of
      behavioral activity states within the postprandial period in low birth weight
      infants. The effect of nutrient intake on sleep profile is dependent on body
      position and time after feed. Mechanistic hypotheses relating sudden infant death
      syndrome to sleeping position may need to take these observations into account.

PMID- 12193676
TI  - Maturity of the adrenal cortex in very preterm infants is related to gestational
      age.
AB  - To study the maturity of the adrenal cortex in preterms born before 33 wk of
      gestation, basal levels of cortisol and cortisone and the cortisol and 17
      hydroxyprogesterone (17-OHP) response to 1 microg/kg adrenocorticotropic hormone
      stimulation were measured in 24 appropriate-for-gestational age preterm infants
      (26-33 wk; 690-1985 g). Gestational age influenced the response of cortisol, 17
      OHP, and the ratio between cortisol/17-OHP in the studied infants. In preterms
      born <30 wk of gestation, levels of cortisol, and the ratio between cortisol/17
      OHP were lower compared with preterms born between 30 and 33 wk. Levels of
      cortisone were higher in preterms born <30 wk, suggesting a lower activity of 11
      beta-hydroxysteroid dehydrogenase that may be related to maturity as well. These
      findings indicate that the adrenal cortex function in preterm infants is closely
      related to the duration of gestation and may be important in neonatal morbidity.

PMID- 12193677
TI  - Trophoblast differentiation modulates the activity of caspases in primary
      cultures of term human trophoblasts.
AB  - Cultured human cytotrophoblasts are more susceptible than syncytiotrophoblasts to
      hypoxia-induced apoptosis. Caspases are cysteine proteases that cleave cellular
      components to effect the apoptotic cascade. We hypothesized that cultured
      cytotrophoblasts exhibit a higher activity of caspases when compared with
      syncytiotrophoblasts. Using western analysis, we demonstrated that the pro
      caspases 3, 6, 8, and 9 are expressed in cytotrophoblasts cultured for 24 h, and
      also, in trophoblasts cultured 72 h when syncytiotrophoblasts have formed.
      Importantly, we found significantly higher activity of all four caspases in
      trophoblasts cultured 24 h compared with cells cultured 72 h. Colchicine and
      DMSO, which hinder trophoblast differentiation, enhanced the activity of all four
      caspases in cells cultured 72 h. Conversely, caspase activity was reduced in
      trophoblasts cultured for 24 h in the presence of epidermal growth factor, which
      enhances differentiation. This effect was most pronounced on caspase 3 and was
      attenuated by addition of the tyrosine kinase inhibitor AG1478. We conclude that
      cytotrophoblasts exhibit a higher activity of caspases 3, 6, 8, and 9 when
      compared with the more differentiated syncytium. This may account for the higher
      susceptibility of cytotrophoblasts to hypoxia-induced apoptosis.

PMID- 12193678
TI  - Prenatal development of gastrointestinal function in the pig and the effects of
      fetal esophageal obstruction.
AB  - Maturation of the fetal gastrointestinal tract (GIT) is influenced by both
      luminal stimuli (e.g. swallowed fluid) and hormonal factors (e.g. endogenous
      cortisol release). The aims of the present study were 1) to investigate GIT
      growth and maturation during the last 20% of gestation in pigs (term = 114 +/- 2
      d), and 2) to investigate the effect of esophageal ligation, to prevent fetal
      swallowing, at 80% to 91% gestation. In normal fetuses, marked increases occurred
      during late gestation in body weight (+95%), relative intestinal weight (+79%, g
      kg(-1) body weight), activity of some digestive enzymes (1.5- to 10-fold), and
      absorption of glucose and intact proteins (3- to 6-fold). Fetuses with ligated
      esophagi had lowered body weight (-20%), reduced intestinal weight (-43%),
      aminopeptidase A activity (-24%), and glucose absorption (-27%), while lactase,
      sucrase, and dipeptidylpeptidase IV activities were increased (+40-50%), compared
      with sham-operated fetuses (all p < 0.05). Other parameters of GIT function
      remained unchanged by esophageal obstruction (absorption of amino acids and
      immunoglobulin, activity of chymosin, amylase, trypsin, chymotrypsin, maltase,
      aminopeptidase N -- all expressed per gram GIT tissue). Ligated fetuses had
      elevated cortisol levels, which is known to stimulate fetal GIT maturation. We
      conclude that the rapid development of GIT function in late gestation is
      diminished by esophageal obstruction, mainly due to slower GIT growth and not
      inhibition of normal functional development of enterocytes.

PMID- 12193679
TI  - The effects of dietary nucleotides on intestinal blood flow in preterm infants.
AB  - Nucleotides (NT) are reported to affect development of the immune and
      gastrointestinal systems, and they are currently added to most term infant
      formulas. In the present study, dietary NT effects on superior mesenteric artery
      blood flow were investigated. Formula-fed preterm infants were studied once with
      a 20 kcal/oz. term infant formula containing 80.6 mg/L of NT (NT+), and once with
      the same formula with no added NT (NT-) (n = 20, gestational age 28.0 +/- 2.2
      wk). A reference group of preterm infants fed human milk was also studied (n =
      20, gestational age 29.0 +/- 1.6 wk). Superior mesenteric artery blood flow
      velocities (BFV) were measured by Doppler ultrasound 15 min before and 30, 60,
      and 90 min after the start of the feed. BFV rose in all infants from baseline to
      30 min after feed initiation, and progressively declined thereafter in infants
      fed NT- or human milk. However, NT+ feedings were associated with a minimal
      change in BFV between 60 and 90 min. As a result, the difference in blood flow
      velocities between baseline and 90 min was significantly greater with the NT+
      versus the NT- feedings for the mean, peak systolic, and end diastolic velocities
      (p = 0.03, 0.05, and 0.03, respectively). BFV after the NT- and human milk
      feedings were similar. These data suggest that orally administered NT are
      associated with effects on the intestinal vasculature.

PMID- 12193680
TI  - Glutamine supplementation and deprivation: effect on artificially reared rat
      small intestinal morphology.
AB  - The mechanisms of how glutamine benefits critically ill patients have not been
      established. The purpose of this study was to determine the effects of dietary
      and endogenously produced glutamine on small intestinal morphology using light
      and transmission electron microscopy in artificially reared rat pups. It was
      hypothesized that deprivation of dietary glutamine leads to intestinal disease
      that is exacerbated by inhibition of glutamine synthetase by methionine
      sulfoximine (MS). Rat pups were placed into five different test groups: The first
      was a reference group that was reared by their mother. The other four groups were
      reared artificially and received a 10% Travasol amino acid solution at 5 g/kg per
      day, which does not contain glutamine, added to a mixture containing
      carbohydrates, lipids, and vitamins. This dose was chosen because it represents
      an approximation of the amount of glutamine these rats would be receiving in a
      normal rat diet (approximately 40 g/kg per day total protein, 10 to 15% of which
      is glutamine + glutamate). The glutamine was manipulated by adding glutamine (Q)
      or MS or both. The four groups were as follows: MS-Q-, MS-Q+, MS+Q-, and MS+Q+.
      Light microscopy revealed the greatest blunting of villus height in the ileum of
      rats from the MS+Q- group when compared with the MS-Q+ group (123 +/- 48.9 micro
      m versus 207 +/- 36 microm, p < 0.05). The other two groups exhibited
      intermediate villus heights, but all were shorter than the villi from the mother
      reared animals. The number of villi per unit length of bowel was also lowest in
      the animals that were treated with MS and not provided with dietary glutamine.
      Transmission electron microscopy demonstrated breakdown of the epithelial
      junctions in the glutamine-deprived and glutamine synthetase-inhibited
      intestines. Glutamine-deprived animals also displayed sloughing of microvilli,
      decreased actin cores, and degeneration of the terminal web. In summary, these
      studies support the hypothesis that glutamine is involved with maintenance of
      intestinal epithelial integrity.

PMID- 12193681
TI  - Effects of fasting on tissue contents of coenzyme A and related intermediates in
      rats.
AB  - Exposure of rats and mice to hyperoxia decreases lung coenzyme A (CoASH)
      contents, with a decrease of 50% observed in adult male Fischer-344 rats exposed
      to >95% O(2) for 48 h. Decreases in lung CoASH levels are not accompanied by
      increases in contents of the mixed glutathione disulfide of CoA, as might be
      expected of a primary oxidative stress on CoASH status. Animals exposed to
      hyperoxia exhibit decreased food intake, and the present studies were to test the
      hypothesis that fasting would decrease lung CoASH contents, thereby suggesting a
      mechanism for the effects of hyperoxia. Adult male Fischer-344 rats were examined
      after 0, 24, or 48 h of fasting (n = 5, 6, and 6, respectively). Fasting for 24
      or 48 h did not affect lung CoASH levels or lung weights, despite 6 and 12%
      losses in body weight. Lung glutathione concentrations (nanomoles per gram of
      tissue) and contents (nanomoles per whole organ) and glutathione disulfide
      contents were 10 to 20% lower in rats fasted for 48 h than in fed rats. Liver
      weights and glutathione and glutathione disulfide contents and concentrations
      were 30 to 70% lower in rats fasted for 24 or 48 h than in fed rats. Hepatic
      CoASH concentrations increased during fasting, but hepatic contents of CoASH
      remained remarkably constant. Liver protein contents (milligrams of protein per
      whole organ) decreased after 24 and 48 h of fasting, but protein concentrations
      (milligrams of protein per gram of tissue) were higher in rats fasted 48 h than
      in fed rats. Overall, glutathione, glutathione disulfide, and protein contents in
      liver and skeletal muscle decreased with fasting, but significant changes in
      CoASH contents were not observed. Diminished food intake in animals does not
      explain the effects of hyperoxia on lung CoASH contents. CoASH and derived
      thioesters participate in many cellular functions, and if depletion of lung CoASH
      during hyperoxia proves to be relevant to mechanisms of lung injury, support of
      mechanisms needed to sustain CoA levels could be helpful in prematurely born
      infants and in adults.

PMID- 12193682
TI  - Epilepsy and the ketogenic diet: assessment of ketosis in children using breath
      acetone.
AB  - High-fat ketogenic diets increase ketones (acetoacetate, beta-hydroxybutyrate,
      and acetone) and are used to treat refractory seizures. Although ketosis is an
      integral aspect of these therapeutic regimens, the direct importance of ketosis
      to seizure control needs further investigation. An examination of this
      relationship requires a reliable, minimally invasive measure of ketosis that can
      be performed frequently. In the present study, we examined the use of breath
      acetone as a measure of ketosis in children with refractory seizures on a classic
      ketogenic diet. Results were compared with breath acetone levels in epilepsy and
      healthy controls. Children on the ketogenic diet had significantly higher fasting
      breath acetone compared with epilepsy or healthy controls (2530 +/- 600 nmol/L
      versus 19 +/- 9 nmol/L and 21 +/- 4 nmol/L, respectively; p < 0.05). One hour
      after consumption of a ketogenic breakfast meal, breath acetone increased
      significantly in epilepsy and healthy controls (p < 0.05), but not in children on
      a ketogenic diet. Children who were on the ketogenic diet for longer periods of
      time had a significantly lower fasting breath acetone (R(2) = 0.55, p = 0.014).
      In one child on the ketogenic diet, breath acetone was determined hourly over a 9
      h period, both by gas chromatography and by a prototype hand-held breath acetone
      analyzer. Preliminary results using this hand-held breath acetone analyzer are
      encouraging. Breath acetone may be a useful tool in examining the relationship
      between ketosis and seizure control and enhancing our understanding of the
      mechanism of the ketogenic diet.

PMID- 12193683
TI  - Impaired spatial learning and hyperactivity in developing rats exposed to
      intermittent hypoxia.
AB  - Obstructive sleep apnea (OSA) is a frequent medical condition and is associated
      with cognitive impairments in adults and with hyperactivity and decreased school
      performance in children. In an adult rodent model, intermittent hypoxia (IH),
      such as occurs in OSA, is associated with neurodegenerative changes in the
      hippocampus and cortex and with spatial learning deficits. Because a unique
      developmental window of neural vulnerability to IH is present, we hypothesized
      that exposure to IH throughout the vulnerable ages would result in increased
      behavioral impairments in the juvenile rat. Rat pups were therefore exposed to
      either room air or IH beginning at postnatal (PN) d 10 until PN d 30. Learning
      and memory were assessed via a standard place-training version of the Morris
      water maze beginning at PN d 25. Locomotor activity was assessed on PN d 29 and
      30. Pups exposed to IH displayed significant spatial learning impairments, and
      exposed male rats but not female rats displayed increased locomotor activity in
      the open field. Collectively, these findings indicate that exposure to IH at an
      age that corresponds to the peak incidence of OSA in children induces substantial
      learning impairment and gender-dependent behavioral hyperactivity in the juvenile
      rat. We postulate that this novel experimental model may allow for future
      exploration of mechanisms underlying the neurobehavioral deficits of children
      with OSA.

PMID- 12193684
TI  - The impact of serum lipid levels on circulating soluble adhesion molecules in
      childhood.
AB  - Cell adhesion molecules play a rather important role in the development of
      atherosclerosis mediating the attachment of monocytes to the endothelium. It has
      also been well established that hyperlipidemia is a risk factor for
      atherosclerosis from childhood. The aim of this study was to investigate whether
      the soluble adhesion molecules correlate with the circulating lipid levels in
      children. The study population consisted of 107 children (64 boys, 43 girls) aged
      6-13 y. Parental history of cardiovascular disease, age, gender, and
      anthropometric parameters were recorded in all children. Blood samples were
      obtained from every child following a 12-hour fasting period. Serum
      triglycerides, total cholesterol, and its fractions as well as plasma levels of P
      and E selectins and adhesion molecules sVCAM-1 and sICAM-1 were determined. After
      controlling for age and body mass index, both sVCAM-1 and sP-selectin levels were
      inversely associated with HDL values (r = -0.33, p = 0.005 and r = -0.39, p =
      0.001, respectively). A significant positive correlation was found between sVCAM
      1 and triglycerides (r = 0.48, p < 0.001). An increment of 10 mg/dL of HDL
      corresponds to about 50% reduction of the odds for endothelial dysfunction
      whereas an increment of 10 mg/dL of triglyceride levels indicates a more than 3
      fold excess risk, using either sP-selectin or sVCAM-1 levels as a surrogate for
      the determination of endothelial dysfunction. We suggest that HDL-C and
      triglycerides correlate in a biologically plausible way with soluble adhesion
      molecules, which therefore could be considered as useful indicators of the
      process of preclinical atherosclerosis even from childhood.

PMID- 12193685
TI  - Inhibition of Na(+)/H(+) exchanger type 3 reduces duration of apnea induced by
      laryngeal stimulation in piglets.
AB  - Reflexes from the larynx induce cessation of breathing in newborn animals. The
      magnitude of respiratory inhibition is inversely related to the level of central
      chemical input. Recent studies indicate that selective inhibition of Na(+)/H(+)
      exchanger type 3 (NHE3) activates CO(2)/H(+)-sensitive neurons, resembling the
      responses evoked by hypercapnic stimuli. Hence, the use of NHE3 inhibitors may
      reduce reflexly mediated respiratory depression and duration of apnea in the
      neonatal period. This possibility was examined in decerebrate, vagotomized,
      ventilated, and paralyzed piglets by testing the effects of i.v. administration
      of NHE3 blocker S8218 on the response of phrenic nerve amplitude, frequency, and
      duration of apnea induced by graded electrical stimulation of the superior
      laryngeal nerve. Superior laryngeal nerve stimulation caused a significant
      decrease in phrenic nerve amplitude, frequency, minute phrenic activity, and
      inspiratory time (all p < 0.01) that was proportional to the level of electrical
      stimulation. Increased levels of stimulation were more likely to induce apnea
      both during and after cessation of stimulation. NHE3 blocker S8218 reduced the
      superior laryngeal nerve stimulation-induced decrease in phrenic nerve amplitude,
      minute phrenic activity, and phrenic nerve frequency (all p < 0.05) and reduced
      superior laryngeal nerve stimulation-induced apnea and duration of
      poststimulation apnea (p < 0.05). In six other pigs the brain concentrations of
      S8218 were measured at different intervals after i.v. administration of the drug
      and were found to be higher in the brain tissue than plasma at all intervals.
      These findings suggest that the use of NHE3 blockers may decrease the duration of
      apnea and possibly reduce the pathophysiologic consequences of potentially life
      threatening apnea in infants.

PMID- 12193686
TI  - Cutting edge: oral type I IFN-tau promotes a Th2 bias and enhances suppression of
      autoimmune encephalomyelitis by oral glatiramer acetate.
AB  - IFN-tau, a novel type I IFN that possesses immunomodulatory properties, lacks
      toxicity normally associated with other type I IFNs. We examined the effects of
      oral IFN-tau alone and in combination with oral glatiramer acetate in
      experimental allergic encephalomyelitis (EAE). By comparison of oral
      administration of IFN-alpha, -beta, and -tau to myelin basic protein-specific TCR
      transgenic mice, we demonstrate these type I IFNs promote secretion of the Th2
      cytokine IL-10 with similar efficiency. Whereas IFN-alpha and -beta induced IFN
      gamma secretion, a Th1 cytokine, IFN-tau did not. Oral IFN-tau alone suppressed
      EAE. When suboptimal doses were administered orally in combination to wild-type
      mice, IFN-tau and glatiramer acetate had a synergistic beneficial effect in
      suppression of EAE. This combination was associated with TGF-beta secretion and
      enhanced IL-10 production. Thus, IFN-tau is a potential candidate for use as a
      single agent or in combination therapy for multiple sclerosis.

PMID- 12193687
TI  - Cutting edge: regulation of T cell activation threshold by CD28 costimulation
      through targeting Cbl-b for ubiquitination.
AB  - Optimal T cell activation requires signaling through the TCR and CD28
      costimulatory receptor. CD28 costimulation is believed to set the threshold for T
      cell activation. Recently, Cbl-b, a ubiquitin ligase, has been shown to
      negatively regulate CD28-dependent T cell activation. In this report, we show
      that CD28 costimulation selectively induces greater ubiquitination and
      degradation of Cbl-b in wild-type T cells than CD3 stimulation alone, and TCR
      induced Cbl-b ubiquitination and degradation are significantly reduced in CD28
      deficient T cells. Stimulation of CD28-deficient T cells with higher doses of
      anti-CD3 results in increased ubiquitination of Cbl-b, which correlates with
      enhanced T cell responses. Our results demonstrate that CD28 costimulation
      regulates the threshold for T cell activation, at least in part, by promoting Cbl
      b ubiquitination and degradation.

PMID- 12193688
TI  - Cutting edge: a novel role for Fas ligand in facilitating antigen acquisition by
      dendritic cells.
AB  - Fas ligand (FasL)-expressing tumor cells are found to effectively mediate
      rejection of the coinoculated FasL negative parental cells while having no effect
      on the growth of histologically distinct tumor cells. These observations indicate
      that FasL induces a specific immune response against Ag derived from FasL-bearing
      tumors and suggest a possible role for FasL in tumor Ag presentation. Indeed,
      tumor cells expressing FasL can efficiently interact with dendritic cells (DCs)
      and this interaction requires the expression of membrane-bound FasL on tumors and
      Fas on DCs. Moreover, DCs cocultured with FasL-expressing tumors are able to
      elicit a tumor-specific immune response in vivo, suggesting that DCs acquire
      tumor Ag during the Fas/FasL-mediated DC-tumor contact. These results identify a
      novel role for FasL in augmenting tumor-DC interactions and subsequent tumor Ag
      acquisition by DCs, and suggest that FasL-expressing tumor cells could be used to
      generate tumor-specific DC vaccines.

PMID- 12193689
TI  - In situ analysis reveals physical interactions between CD11b+ dendritic cells and
      antigen-specific CD4 T cells after subcutaneous injection of antigen.
AB  - In situ staining techniques were used to visualize physical interactions between
      dendritic cell subsets and naive Ag-specific CD4 T cells in the lymph node.
      Before injection of Ag, CD8(+) dendritic cells and naive OVA-specific CD4 T cells
      were uniformly distributed throughout the T cell-rich paracortex, whereas
      CD11b(+) dendritic cells were located mainly in the outer edges of the paracortex
      near the B cell-rich follicles. Many OVA-specific CD4 T cells were in contact
      with CD8(+) dendritic cells in the absence of OVA. Within 24 h after s.c.
      injection of soluble OVA, the OVA-specific CD4 T cells redistributed to the outer
      paracortex and interacted with CD11b(+), but not CD8(+) dendritic cells. This
      behavior correlated with the uptake of OVA and the presence of peptide-MHC
      complexes on the surface of CD11b(+) dendritic cells, and subsequent IL-2
      production by the Ag-specific CD4 T cells. These results are consistent with the
      possibility that CD11b(+) dendritic cells play a central role in the activation
      of CD4 T cells in response to s.c. Ag.

PMID- 12193690
TI  - Shaping gene expression in activated and resting primary macrophages by IL-10.
AB  - IL-10 regulates inflammation by reducing cytokine and chemokine production from
      activated macrophages. We performed microarray experiments to identify possible
      effector molecules of IL-10 and to investigate the global effect of IL-10 on the
      transcriptional response induced in LPS-activated macrophages. To exclude
      background effects of endogenous IL-10, macrophages from IL-10-deficient mice
      were used. IL-10 up-regulated expression of a small number of genes (26 and 37
      after 45 min and 3 h, respectively), including newly identified and previously
      documented targets such as suppressor of cytokine signaling-3 and IL-1 receptor
      antagonist. However, the activation program triggered by LPS was profoundly
      affected by IL-10. IL-10 repressed 62 and further increased 15 of 259 LPS-induced
      genes. For all genes examined, the effects of IL-10 were determined to be STAT3
      dependent. These results suggest that IL-10 regulates STAT3-dependent pathways
      that selectively target a broad component of LPS-induced genes at the mRNA level.

PMID- 12193691
TI  - Granulocyte-macrophage colony-stimulating factor induces an expression program in
      neonatal microglia that primes them for antigen presentation.
AB  - Neonatal microglial cells respond to GM-CSF and M-CSF by acquiring different
      morphologies and phenotypes. To investigate the extent and consequences of this
      process, a global gene expression analysis was performed, with significant
      changes in transcript levels confirmed by biochemical analyses. Primary murine
      microglial cells underwent substantial expression reprogramming after treatment
      with GM-CSF or M-CSF with many differentially expressed transcripts important in
      innate and adaptive immunity. In particular, many gene products involved in Ag
      presentation were induced by GM-CSF, but not M-CSF, thus potentially priming
      relatively quiescent microglia cells for Ag presentation. This function of GM-CSF
      is distinct from its primary function in cell proliferation and survival.

PMID- 12193692
TI  - Intracellular single-chain variable fragments directed to the Src homology 2
      domains of Syk partially inhibit Fc epsilon RI signaling in the RBL-2H3 cell
      line.
AB  - Intracellular expression of Ab fragments has been efficiently used to inactivate
      therapeutic targets, oncogene products, and to induce viral resistance in plants.
      Ab fragments expressed in the appropriate cell compartment may also help to
      elucidate the functions of a protein of interest. We report in this study the
      successful targeting of the protein tyrosine kinase Syk in the RBL-2H3 rat
      basophilic leukemia cell line. We isolated from a phage display library human
      single-chain variable fragments (scFv) directed against the portion of Syk
      containing the Src homology 2 domains and the linker region that separates them.
      Among them, two scFv named G4G11 and G4E4 exhibited the best binding to Syk in
      vivo in a yeast two-hybrid selection system. Stable transfectants of RBL-2H3
      cells expressing cytosolic G4G11 and G4E4 were established. Immunoprecipitation
      experiments showed that intracellular G4G11 and G4E4 bind to Syk, but do not
      inhibit the activation of Syk following FcepsilonRI aggregation, suggesting that
      the scFv do not affect the recruitment of Syk to the receptor. Nevertheless,
      FcepsilonRI-mediated calcium mobilization and the release of inflammatory
      mediators are inhibited, and are consistent with a defect in Bruton's tyrosine
      kinase and phospholipase C-gamma2 tyrosine phosphorylation and activation.
      Interestingly, FcepsilonRI-induced mitogen-activated protein kinase
      phosphorylation is not altered, suggesting that intracellular G4G11 and G4E4 do
      not prevent the coupling of Syk to the Ras pathway, but they selectively inhibit
      the pathway involving phospholipase C-gamma2 activation.

PMID- 12193693
TI  - Two phenotypically distinct subsets of spleen dendritic cells in rats exhibit
      different cytokine production and T cell stimulatory activity.
AB  - We recently reported that splenic dendritic cells (DC) in rats can be separated
      into CD4(+) and CD4(-) subsets and that the CD4(-) subset exhibited a natural
      cytotoxic activity in vitro against tumor cells. Moreover, a recent report
      suggests that CD4(-) DC could have tolerogenic properties in vivo. In this study,
      we have analyzed the phenotype and in vitro T cell stimulatory activity of
      freshly isolated splenic DC subsets. Unlike the CD4(-) subset, CD4(+) splenic DC
      expressed CD5, CD90, and signal regulatory protein alpha molecules. Both fresh
      CD4(-) and CD4(+) DC displayed an immature phenotype, although CD4(+) cells
      constitutively expressed moderate levels of CD80. The half-life of the CD4(-),
      but not CD4(+) DC in vitro was extremely short but cells could be rescued from
      death by CD40 ligand, IL-3, or GM-CSF. The CD4(-) DC produced large amounts of
      the proinflammatory cytokines IL-12 and TNF-alpha and induced Th1 responses in
      allogeneic CD4(+) T cells, whereas the CD4(+) DC produced low amounts of IL-12
      and no TNF-alpha, but induced Th1 and Th2 responses. As compared with the CD4(+)
      DC that strongly stimulated the proliferation of purified CD8(+) T cells, the
      CD4(-) DC exhibited a poor CD8(+) T cell stimulatory capacity that was
      substantially increased by CD40 stimulation. Therefore, as previously shown in
      mice and humans, we have identified the existence of a high IL-12-producing DC
      subset in the rat that induces Th1 responses. The fact that both the CD4(+) and
      CD4(-) DC subsets produced low amounts of IFN-alpha upon viral infection suggests
      that they are not related to plasmacytoid DC.

PMID- 12193694
TI  - Expression of CD28 by bone marrow stromal cells and its involvement in B
      lymphopoiesis.
AB  - Young mice lacking CD28 have normal numbers of peripheral B cells; however,
      abnormalities exist in the humoral immune response that may result from an
      intrinsic defect in the B cells. The goal of this study was to assess whether
      CD28 could be involved in the development of B cells. CD28 mRNA was detected
      preferentially in the fraction of bone marrow enriched for stromal cells. Flow
      cytometry and RT-PCR analysis demonstrated that CD28 was also expressed by
      primary-cultured stromal cells that supported B lymphopoiesis. Confocal
      microscopy revealed that in the presence of B-lineage cells, CD28 was localized
      at the contact interface between B cell precursors and stromal cells. In
      addition, CD80 was detected on 2-6% of freshly isolated pro- and pre-B cells, and
      IL-7 stimulation led to induction of CD86 on 15-20% of pro- and pre-B cells. We
      also observed that stromal cell-dependent production of B-lineage cells in vitro
      was greater on stromal cells that lacked CD28. Finally, the frequencies of B
      lineage precursors in the marrow from young (4- to 8-wk-old) CD28(-/-) mice were
      similar to those in wild-type mice; however, older CD28(-/-) mice (15-19 mo old)
      exhibited a 30% decrease in pro-B cells and a 50% decrease in pre-B cells vs age
      matched controls. Our results suggest that CD28 on bone marrow stromal cells
      participates in stromal-dependent regulation of B-lineage cells in the bone
      marrow. The localization of CD28 at the stromal cell:B cell precursor interface
      suggests that molecules important for T cell:B cell interactions in the periphery
      may also participate in stromal cell:B cell precursor interactions in the bone
      marrow.

PMID- 12193695
TI  - Quantitative differences in chemokine receptor engagement generate diversity in
      integrin-dependent lymphocyte adhesion.
AB  - Chemokines control the specificity of lymphocyte homing. Numerous chemokines have
      been identified but the significance of redundancy in chemokine networks is
      unexplained. Here we investigated the biological significance of distinct
      chemokines binding to the same receptor. Among CCR4 ligands, skin vessels
      endothelial cells present C-C chemokine ligand (CCL) 17 but not CCL22 consistent
      with CCL17 involvement in T lymphocyte arrest on endothelial cells. However,
      CCL22 is much more powerful than CCL17 in the induction of rapid integrin
      dependent T cell adhesion on VCAM-1 under conditions of physiological flow. The
      dominance of CCL22 over CCL17 extends to other CCR4-mediated phenomena such as
      receptor desensitization and internalization and correlates with the peculiar
      kinetics of CCR4 engagement by the two ligands. A similar phenomenological
      pattern is also shown for CXC chemokine ligand 9 and CXC chemokine ligand 11,
      which share binding to CXCR3. Our analysis shows how quantitative variations in
      chemokine receptor expression level and ligand engagement may alter the
      selectivity of integrin-dependent lymphocyte adhesive responses, suggesting a
      mechanism by which chemokine networks may either generate or break the
      specificity of lymphocyte subset recruitment.

PMID- 12193696
TI  - Follicular dendritic cell-mediated up-regulation of CXCR4 expression on CD4 T
      cells and HIV pathogenesis.
AB  - Follicular dendritic cells (FDCs) represent a major reservoir of HIV, and active
      infection occurs surrounding these cells, suggesting that this microenvironment
      is highly conducive to virus transmission. Because CD4 T cells around FDCs in
      germinal centers express the HIV coreceptor, CXCR4, whereas CD4 lymphocytes in
      many other sites do not, it prompted the hypothesis that FDCs may increase CXCR4
      expression on CD4 T cells, thereby facilitating infection. To test this, HIV
      receptor/coreceptor expression was determined on CD4 T cells cultured with or
      without FDCs, and its consequence to infection was assessed by measuring virus
      binding and entry. FDCs had little effect on CCR5 or CD4 expression but increased
      CXCR4 expression on CD4 T cells. FDC-mediated up-regulation of CXCR4 on CD4 T
      cells occurred by 24 h and was sustained for at least 96 h in vitro, and FDC-CD4
      T cell contact was necessary. Importantly, increased CXCR4 expression directly
      correlated with increased binding and entry of HIV-1 X4 isolates. Furthermore,
      CD4(+)CD57(+) germinal center T cells expressed high levels of CXCR4 and
      supported enhanced entry of X4 HIV compared with other CD4 T cells from the same
      tissue. Thus, in addition to serving as a reservoir of infectious virus, FDCs
      render surrounding germinal center T cells highly susceptible to infection with
      X4 isolates of HIV-1.

PMID- 12193697
TI  - Murine malaria is exacerbated by CTLA-4 blockade.
AB  - Cytolytic T lymphocyte-associated Ag-4 (CD152) is a negatively regulating
      molecule, which is primarily expressed on T cells following their activation. In
      this study, we have examined the role of CTLA-4 expression in experimental blood
      stage malaria. Similar to human malaria, CTLA-4 is expressed on CD4(+) T cells of
      C57BL/6 mice after infection with Plasmodium berghei. A kinetic analysis revealed
      that CTLA-4 expression was increased on day 5 postinfection and reached a peak on
      day 9 postinfection, when almost 10% of splenic CD4(+) T cells expressed CTLA-4.
      Blockade of CTLA-4 in vivo by a specific mAb and subsequent challenge with P.
      berghei caused neurological signs reminiscent of murine cerebral malaria and
      earlier death. Histologic examination of brain sections from anti-CTLA-4-treated
      mice revealed pathologic changes such as hemorrhages and edema, which were absent
      in control mice. Furthermore, treatment with anti-CTLA-4 also reversed the
      extensive loss of CD4(+) T cells and the suppressed T cell response occurring
      during blood-stage malaria. Our data suggest that CTLA-4 expression prevents
      immune pathology by restricting T cell activation during malaria. They also
      indicate that the development of cerebral malaria is mediated by a failure to
      down-regulate T cell activation.

PMID- 12193698
TI  - Requirement for RhoA kinase activation in leukocyte de-adhesion.
AB  - Leukocyte migration from bloodstream to tissue requires rapid coordinated
      regulation of integrin-dependent adhesion and de-adhesion. Whether de-adhesion is
      an active process mediated by a distinct signaling pathway(s) or a passive decay
      of initial adhesion remains undetermined. We found that blockade of RhoA with C3
      exoenzyme or inhibition of RhoA kinase by the specific inhibitor Y-27632 enhanced
      phorbol ester-stimulated alpha(4)beta(1)-dependent adhesion of Jurkat cells at 30
      min. Similarly, Y-27632 treatment increased stimulated beta(2) integrin-dependent
      neutrophil adhesion at 30 min but not at 5 min. Because reduced de-adhesion could
      mimic augmentation of adhesion at later time points, we developed an assay to
      measure de-adhesion specifically. Treatment of phorbol ester-or bacterial
      chemoattractant peptide-but not Mn(2+)-stimulated neutrophils adherent to serum
      coated plastic or endothelial cells with Y-27632 or C3 exoenzyme markedly reduced
      the rate of de-adhesion, while markedly increasing their spreading. RhoA kinase
      inhibitor effects on de-adhesion and spreading were reversed by treatment with
      the cytoskeletal-disrupting agent cytochalasin D. Treatment with Y-27632
      influenced neither integrin activation epitope nor integrin clustering. We
      conclude that activation of RhoA kinase promotes leukocyte de-adhesion by
      inhibiting cytoskeletal-dependent spreading, and that these effects of RhoA
      kinase constitute a new mechanism for regulation of integrin receptor avidity.

PMID- 12193700
TI  - CCR6 colocalizes with CD18 and enhances adhesion to activated endothelial cells
      in CCR6-transduced Jurkat T cells.
AB  - CCR6 is expressed by memory T cells (mTC) and is a requirement for efficient
      arrest of a subset of mTC to activated human dermal microvascular endothelial
      cells (HDMEC) under physiologic shear stress. We now address whether CCR6 alone
      is sufficient to induce arrest of a model T cell line (Jurkat) that shows low
      expression of all CCRs tested (CCR1-10). Herein, we transduced Jurkat (JK) T
      cells expressing fucosyltransferase VII with a chimeric chemokine receptor
      consisting of CCR6 fused to enhanced green fluorescent protein. In contrast to
      the starting JK lines, the resulting cell line (JK fucosyltransferase VII-CCR6)
      migrated 6-fold better to CCL20 in chemotaxis assays, arrested in response to
      CCL20 that was immobilized to plastic, and demonstrated a 2.5-fold increase in
      adhesion to activated HDMEC (p = 0.001). Adhesion was blocked by anti-CD18 mAb (p
      = 0.005) but not by anti-CD49d mAb (p = 0.3). After arrest on recombinant
      substrates, CCR6 clustered on the surface as detected by real-time observation of
      enhanced green fluorescent protein fluorescence. Dual-label confocal microscopy
      revealed that LFA-1 (CD18 and CD11a), but not CXCR4, colocalized with clustered
      CCR6 in the presence of immobilized CCL20. Thus, the functional expression of
      CCR6 is sufficient to provide the chemokine signaling necessary to induce arrest
      of a JK T cell line to activated HDMEC. Clustering of CCR6 and coassociation with
      critical integrins may serve to strengthen adhesion between T cells and activated
      endothelial cells.

PMID- 12193699
TI  - Enhancement of MHC class II-restricted responses by receptor-mediated uptake of
      peptide antigens.
AB  - Peptides, either as altered peptide ligands, competitors, or vaccines, offer an
      outstanding potential for regulating immune responses because of their exquisite
      specificity. However, a major problem associated with peptide therapies is that
      they are poorly taken up by APCs. Because of poor bioavailability, high
      concentrations and repeated treatments are required for peptide therapies in
      vivo. To circumvent this problem, we tested whether covalently coupling a peptide
      T cell determinant, OVA(323-339), to transferrin (Tf) enhances APC uptake and
      presentation as monitored by Th cell activation. Functional analysis of the Tf
      peptide conjugates revealed that the conjugates were presented 10,000- and 100
      fold more effectively by B cells than intact Ag and free peptide, respectively.
      Furthermore, we demonstrate that the Tf-peptide conjugates are taken up by B
      cells through a receptor-mediated process and subsequently delivered to the
      lysosomal compartment. Using an adoptive transfer assay, we show that that the Tf
      peptide complexes are 100-fold more effective in vivo than the free peptide in
      activating CD4(+) T cells by following an early activation marker, CD69. Our
      results demonstrate that coupling peptides to Tf enhances peptide presentation,
      thereby making it possible to take full advantage of peptide-specific therapies
      in modulating T cell responses.

PMID- 12193701
TI  - Suppressor of cytokine signaling 1 inhibits cytokine induction of CD40 expression
      in macrophages.
AB  - CD40 is a type I membrane-bound molecule belonging to the TNFR superfamily that
      is expressed on various immune cells including macrophages and microglia. The
      aberrant expression of CD40 is involved in the initiation and maintenance of
      various human diseases including multiple sclerosis, arthritis, atherosclerosis,
      and Alzheimer's disease. Inhibition of CD40 signaling has been shown to provide a
      significant beneficial effect in a number of animal models of human diseases
      including the aforementioned examples. We have previously shown that IFN-gamma
      induces CD40 expression in macrophages and microglia. IFN-gamma leads to STAT
      1alpha activation directly and up-regulation of NF-kappaB activity due to the
      secretion and subsequent autocrine signaling of TNF-alpha. However, TNF-alpha
      alone is not capable of inducing CD40 expression in these cells. Suppressor of
      cytokine signaling 1 protein (SOCS-1) is a cytokine-inducible Src homology 2
      containing protein that regulates cytokine receptor signaling by inhibiting STAT
      1alpha activation via a specific interaction with activated Janus kinase 2. Given
      the important role of CD40 in inflammatory events in the CNS as well as other
      organ systems, it is imperative to understand the molecular mechanisms
      contributing to both CD40 induction and repression. We show that ectopic
      expression of SOCS-1 abrogates IFN-gamma-induced CD40 protein expression, mRNA
      levels, and promoter activity. Additionally, IFN-gamma-induced TNF-alpha
      secretion, as well as STAT-1alpha and NF-kappaB activation, are inhibited in the
      presence of SOCS-1. We conclude that SOCS-1 inhibits cytokine-induced CD40
      expression by blocking IFN-gamma-mediated STAT-1alpha activation, which also then
      results in suppression of IFN-gamma-induced TNF-alpha secretion and subsequent NF
      kappaB activation.

PMID- 12193702
TI  - Endogenous H/K ATPase beta-subunit promotes T cell tolerance to the
      immunodominant gastritogenic determinant.
AB  - A CD4(+) T cell response to the gastric H/K ATPase beta-subunit (H/Kbeta) is
      required for the onset of experimental autoimmune gastritis in BALB/c mice. The
      extent to which endogenous H/Kbeta contributes toward the tolerance of the
      H/Kbeta-specific T cell repertoire in normal individuals is not known. By
      comparison of T cell responses in H/Kbeta-deficient (o/o) and H/Kbeta-expressing
      BALB/c mice, in this work we show that the endogenous H/Kbeta autoantigen plays a
      major role in the tolerance of pathogenic H/Kbeta-specific T cells. First, T cell
      dependent Ab responses to the H/Kbeta Ag were enhanced in H/K ATPase-immunized
      H/Kbeta-deficient mice compared with wild-type mice. Second, peptide immunization
      experiments indicated that immune responses to the major gastritogenic epitope of
      the H/K ATPase, namely H/Kbeta(253-277), were significantly more vigorous in
      H/Kbeta-deficient mice compared with wild-type mice. Third, unfractionated
      splenocytes from H/Kbeta-deficient mice, but not H/Kbeta-expressing mice, induced
      autoimmune gastritis after adoptive transfer to BALB/c nude mice. The enhanced
      responses to H/Kbeta in H/Kbeta-deficient mice were shown to be intrinsic to
      CD4(+)CD25(-) T cells rather than a change in status of CD4(+)CD25(+) regulatory
      T cells. We conclude from these studies that the H/Kbeta-specific T cells in wild
      type mice represent the residue of a T cell repertoire, directed toward a single
      determinant, that has been subjected to partial tolerance induction.

PMID- 12193703
TI  - Distinct response of human B cell subpopulations in recognition of an innate
      immune signal, CpG DNA.
AB  - Innate immunity has recently gained renewed interest in its ability to regulate
      adaptive immunity. Among the innate immune signals, CpG DNA has revealed its
      potential as a vaccine adjuvant. However, the cellular mechanism for the effect
      of CpG DNA on the humoral immune response is not well understood. Here, we
      investigated the effects of CpG DNA on human B cell differentiation using highly
      purified B cell subsets: naive, germinal center (GC), and memory B cells. In the
      in vitro culture system that mimics the primary or secondary immune response in
      vivo, CpG DNA markedly augmented the proliferation and generation of plasma cells
      from naive and memory B cells. CpG DNA dramatically increased plasma cell
      generation from GC B cells. However, CpG DNA did not have effect on memory B cell
      generation from GC B cells. These results suggest that CpG DNA potentiates the B
      cell adaptive immune response by enhancing terminal differentiation, but does not
      affect the generation of memory B cells.

PMID- 12193704
TI  - 1,25(OH)2 vitamin D3-stimulated osteoclast formation in spleen-osteoblast
      cocultures is mediated in part by enhanced IL-1 alpha and receptor activator of
      NF-kappa B ligand production in osteoblasts.
AB  - We examined the ability of 1,25 (OH)(2) vitamin D(3) (Vit D) to stimulate
      osteoclast-like cell (OCL) formation in cocultures of spleen cells and primary
      calvarial osteoblasts from wild-type (WT) and IL-1R type 1-deficient (knockout;
      KO) mice. Vit D dose dependently increased OCL in cocultures containing WT
      osteoblasts. In contrast, there was a 90% reduction in OCL numbers in cocultures
      containing KO osteoblasts. In cocultures with either WT or KO osteoblasts,
      treatment with Vit D increased receptor activator of NF-kappaB ligand mRNA by 17
      , 19-, or 3.5-fold, respectively. Vit D decreased osteoprotegerin mRNA to
      undetectable in all groups. Intracellular IL-1alpha protein increased after Vit D
      treatment in cocultures containing WT, but not KO osteoblasts. We also examined
      direct effects of Vit D, IL-1alpha, and their combination on gene expression in
      primary osteoblasts. In WT cells, Vit D and IL-1 stimulated receptor activator of
      NF-kappaB ligand mRNA expression by 3- and 4-fold, respectively, and their
      combination produced a 7-fold increase. Inhibition of osteoprotegerin mRNA in WT
      cells was partial with either agent alone and greatest with their combination. In
      KO cells, only Vit D stimulated a response. IL-1 alone increased IL-1alpha
      protein expression in WT osteoblasts. However, in combination with Vit D, there
      was a synergistic response (100-fold increase). In KO cultures, there were no
      effects of IL-1, Vit D, or their combination on IL-1alpha protein. These results
      demonstrate interactions between IL-1 and Vit D in primary osteoblasts that
      appear important in both regulation of IL-1alpha production and the ability of
      Vit D to support osteoclastogenesis.

PMID- 12193705
TI  - FDC-SP, a novel secreted protein expressed by follicular dendritic cells.
AB  - To define better the molecular basis for follicular dendritic cell (FDC)
      function, we used PCR-based cDNA subtraction to identify genes specifically
      expressed in primary FDC isolated from human tonsils. In this work we report the
      discovery of a novel gene encoding a small secreted protein, which we term FDC-SP
      (FDC secreted protein). The FDC-SP gene lies on chromosome 4q13 adjacent to
      clusters of proline-rich salivary peptides and C-X-C chemokines. Human and mouse
      FDC-SP proteins are structurally unique and contain a conserved N-terminal
      charged region adjacent to the leader peptide. FDC-SP has a very restricted
      tissue distribution and is expressed by activated FDCs from tonsils and TNF-alpha
      activated FDC-like cell lines, but not by B cell lines, primary germinal center B
      cells, or anti-CD40 plus IL-4-activated B cells. Strikingly, FDC-SP is highly
      expressed in germinal center light zone, a pattern consistent with expression by
      FDC. In addition, FDC-SP is expressed in leukocyte-infiltrated tonsil crypts and
      by LPS- or Staphylococcus aureus Cowan strain 1-activated leukocytes, suggesting
      that FDC-SP can also be produced in response to innate immunity signals. We
      provide evidence that FDC-SP is posttranslationally modified and secreted and can
      bind to the surface of B lymphoma cells, but not T lymphoma cells, consistent
      with a function as a secreted mediator acting upon B cells. Furthermore, we find
      that binding of FDC-SP to primary human B cells is markedly enhanced upon
      activation with the T-dependent activation signals such as anti-CD40 plus IL-4.
      Together our data identify FDC-SP as a unique secreted peptide with a distinctive
      expression pattern within the immune system and the ability to specifically bind
      to activated B cells.

PMID- 12193706
TI  - Promotion of skin graft tolerance across MHC barriers by mobilization of
      dendritic cells in donor hemopoietic cell infusions.
AB  - Flt3 ligand (FL) dramatically increases the number of immunostimulatory dendritic
      cells (DC) and their precursors in bone marrow (BM) and secondary lymphoid
      tissues. Herein we tested the ability of FL-mobilized donor hemopoietic cells to
      promote induction of skin graft tolerance across full MHC barriers. C57BL/10
      (B10; H2(b), IE(-)) mice were given 10(8) spleen cells (SC) from normal or FL
      treated, H-2-mismatched B10.D2 (H2(d), IE(+)) donors i.v. on day 0, 200 mg/kg
      i.p. cyclophosphamide on day 2, and 10(7) T cell-depleted BM cells from B10.D2
      mice on day 3. B10.D2 skin grafting was performed on day 14. Indefinite allograft
      survival (100 days) was induced in recipients of FL-SC, but not in mice given
      normal SC. Tolerance was associated with blood macrochimerism and was confirmed
      by second-set skin grafting with donor skin 100 days after the first graft. In
      tolerant mice, peripheral donor-reactive T cells expressing TCR Vbeta11 were
      deleted selectively. Immunocompetence of tolerant FL-SC-treated mice was proven
      by rapid rejection of third-party skin grafts. To our knowledge this is the first
      report that mobilization of DC in donor cell infusions can be used to induce skin
      graft tolerance across MHC barriers, accompanied by specific deletion of donor
      reactive T cells.

PMID- 12193707
TI  - NK T cell precursors exhibit differential cytokine regulation and require Itk for
      efficient maturation.
AB  - NK T cells are a lymphocyte lineage that is selected by CD1d and is characterized
      by the ability to rapidly secrete large amounts of both IFN-gamma and IL-4 after
      TCR stimulation. Using reactivity to CD1d tetramers to define presumptive NK T
      cells, several NK T cell progenitor populations were characterized based upon NK
      marker expression and CD4 vs CD8 expression. The earliest populations were found
      to be negative for NK markers and could proliferate to IL-7, while mature NK T
      cells did not. The NK1.1(-) NK T cell progenitors were capable of up-regulating
      NK1.1 when transferred in vivo. Upon stimulation, the NK1.1(-) populations
      secrete IL-4, but little IFN-gamma. As the cells mature and up-regulate NK1.1,
      they acquire the ability to secrete IFN-gamma. Finally, the Tec family tyrosine
      kinase Itk is necessary for optimal NK1.1 up-regulation and hence final
      maturation of NK T cells. The itk(-/-) mice also display a progressive decrease
      in NK T cells in older animals, suggesting a further role in peripheral
      maintenance.

PMID- 12193708
TI  - Immunomodulatory effects of the liver: deletion of activated CD4+ effector cells
      and suppression of IFN-gamma-producing cells after intravenous protein
      immunization.
AB  - The liver is tolerogenic in many situations, including as an allograft and during
      the response to allogeneic MHC expressed on hepatocytes. The majority of data
      that address this issue focus on endogenous Ags. Little is known about CD4(+) T
      cells and their fate under tolerizing conditions, especially with respect to
      fully differentiated CD4(+) effector T cells. In this study, we used the adoptive
      transfer of populations of TCR-transgenic CD4(+) T cells, skewed toward the Th1
      or Th2 phenotype, to test whether either apoptotic or immune deviation mechanisms
      apply to cytokine-producing CD4(+) T cells that enter the liver. After transfer,
      Th1 and Th2 cells could be detected up to 25 days in lymphoid organs and the
      liver. Intravenous high dose Ag application resulted in accumulation,
      proliferation, and subsequent deletion of effector cells within the liver. Th1
      cells lost their capacity to produce cytokines, whereas IL-4 expression was
      sustained within Th2 cells from the liver. However, there was no evidence for a
      deviation of Th1-programmed cells toward a Th2 (IL-4) or regulatory T cell (IL
      10) pattern of cytokine expression. We used isolated populations of liver-derived
      APCs to test whether the liver had the capacity to impose a bias toward IL-4
      expression in T cells. These experiments showed that liver sinusoidal endothelial
      cells selectively suppress the expansion of IFN-gamma-producing cells, yet they
      promote the outgrowth of IL-4-expressing Th2 cells, creating an immune
      suppressive milieu within this organ. These data suggest that presentation of Ags
      in the liver leads to modulation of immune response in terms of quantity and
      quality.

PMID- 12193711
TI  - The Dermatophagoides pteronyssinus group 2 allergen contains a universally
      immunogenic T cell epitope.
AB  - The use of T cell epitope-containing peptides for the induction of anergy in
      allergen sensitization is limited by genetic restriction that could be
      circumvented by using universally immunogenic epitopes. We attempted to identify
      such epitopes on Dermatophagoides pteronyssinus group 2 allergen (Der p 2), a
      major allergen of D. pteronyssinus T cells from BALB/c (H-2(d)), C57BL/6 (H
      2(b)), C3H (H-2(k)), and SJL (H-2(s)) mice that were immunized with rDer p 2,
      recognized an immunodominant region encompassing residues 21-35. A synthetic 21
      35 peptide (p21-35) induced strong dose-dependent in vitro T cell proliferation
      with cells of the four mouse strains and required processing for MHC class II
      presentation. Substitution of Ile(28) with Ala resulted in reduction of T cell
      proliferation in each strain. Ile(28) could represent an important MHC class II
      anchoring residue for T cell response to p21-35. An immunodominant T cell epitope
      of Der p 2 therefore behaves as a universal epitope and could be a suitable
      candidate for T cell anergy induction.

PMID- 12193712
TI  - T cell response to preproinsulin I and II in the nonobese diabetic mouse.
AB  - Immunization against insulin, insulin B chain, or B chain peptide B(9-23)
      (preproinsulin peptide II(33-47)) prevents diabetes in the nonobese diabetic
      (NOD) mouse. Whether or not peptide II(33-47) is the only proinsulin determinant
      recognized by CD4 T cells remains unclear. Using two peptide libraries spanning
      the entire sequence of preproinsulin I and preproinsulin II, respectively, we
      identified T cells specific for four proinsulin epitopes within the islet cell
      infiltrate of prediabetic female NOD mice. These epitopes were among immunogenic
      epitopes to which a T cell response was detected after immunization of NOD mice
      with individual peptides in CFA. Immunogenic epitopes were found on both isoforms
      of insulin, especially proinsulin II, which is the isoform expressed in the
      thymus. The autoimmune response to proinsulin represented only part of the immune
      response to islet cells within the islet cell infiltrate in 15-wk-old NOD mice.
      This is the first systematic study of preproinsulin T cell epitopes in the NOD
      mouse model.

PMID- 12193710
TI  - Stimulation of Th1-polarizing cytokines, C-C chemokines, maturation of dendritic
      cells, and adjuvant function by the peptide binding fragment of heat shock
      protein 70.
AB  - The peptide binding C-terminal portion of heat shock protein (HSP)70 (aa 359-610)
      stimulates human monocytes to produce IL-12, TNF-alpha, NO, and C-C chemokines.
      The N-terminal, ATPase portion (HSP70(1-358)) failed to stimulate any of these
      cytokines or chemokines. Both native and the truncated HSP70(359-610) stimulation
      of chemokine production is mediated by the CD40 costimulatory molecule.
      Maturation of dendritic cells was induced by stimulation with native HSP70, was
      not seen with the N-terminal HSP70(1-358), but was enhanced with HSP70(359-610),
      as demonstrated by up-regulation of CD83, CCR7, CD86, CD80, and HLA class II. In
      vivo studies in macaques showed that immunization with HSP70(359-610) enhances
      the production of IL-12 and RANTES. Immunization with peptide-bound HSP70(359
      610) in mice induced higher serum IgG2a and IgG3 Abs than the native HSP70-bound
      peptide. This study suggests that the C-terminal, peptide-binding portion of
      HSP70 is responsible for stimulating Th1-polarizing cytokines, C-C chemokines,
      and an adjuvant function.

PMID- 12193709
TI  - Solid-phase epitope recovery: a high throughput method for antigen identification
      and epitope optimization.
AB  - Self tolerance to MHC class I-restricted nonmutated self Ags is a significant
      hurdle to effective cancer immunotherapy. Compelling evidence is emerging that
      altered peptide ligands can be far more immunogenic than their corresponding
      native epitopes; however, there is no way to reliably predict which modifications
      will lead to enhanced native epitope-specific immune responses. We reasoned that
      this limitation could be overcome by devising an empirical screen in which the
      nearly complete combinatorial spectrum of peptides of optimal length can be
      rapidly assayed for reactivity with a MHC class I-restricted cytotoxic T cell
      clone. This method, solid-phase epitope recovery, quantitatively ranks all
      reactive peptides in the library and allows selection of altered peptide ligands
      having desirable immunogenic properties of interest. In contrast to rationally
      designed MHC anchor-modified peptides, peptides identified by the present method
      are highly substituted in predicted TCR contact residues and can reliably
      activate and expand effector cell populations in vitro which lyse target cells
      presenting the wild-type epitope. We demonstrate that solid-phase epitope
      recovery peptides corresponding to a poorly immunogenic epitope of the melanoma
      Ag, gp100, can reliably induce wild-type peptide-specific CTL using normal donor
      T cells in vitro. Furthermore, these peptides can complement one another to
      induce these responses in an overwhelming majority of normal individuals in
      vitro. These data provide a rationale for the design of superior vaccines
      comprising a mixture of structurally diverse yet functionally convergent
      peptides.

PMID- 12193713
TI  - Role of disulfide bonds in regulating antigen processing and epitope selection.
AB  - Knowledge of the events governing Ag processing and epitope selection within APC
      is key to the development of novel immunotherapeutic strategies for infectious
      diseases, cancer, and autoimmunity. The influence of disulfides and Ag reduction
      on the hierarchy of epitope presentation via MHC class II molecules was
      investigated through studies of a self Ag, IgG kappa. HLA-DR4(+) B cells
      preferentially present an immunodominant IgG-derived epitope, kappaI, relative to
      a subdominant kappaII peptide. kappaI contains a cysteine masked within the
      native Ag via an intrachain disulfide, the latter of which is reduced during Ag
      processing. Mutagenesis of this cysteine as well as others within kappa minimally
      perturbed the abundance and overall conformation of IgG. Yet, disruptions in
      disulfide bonding within this Ag influenced the selective display of class II
      restricted dominant and subdominant T cell epitopes. Presentation of the kappaI
      epitope from both native and variant IgG was dependent upon cellular expression
      of IFN-gamma-inducible lysosomal thiol reductase. These studies indicate that
      disulfide bonds regulate Ag processing both locally and at distant sites, thus
      influencing epitope selection within the class II pathway.

PMID- 12193715
TI  - The subpopulation of CD4+CD25+ splenocytes that delays adoptive transfer of
      diabetes expresses L-selectin and high levels of CCR7.
AB  - Recently, CD4(+)CD25(+) T cells have been implicated in the control of diabetes,
      suggesting that the inflamed islets of Langerhans in prediabetic NOD mice are
      under peripheral immune surveillance. Here we show that CD4(+)CD25(+) splenocytes
      inhibit diabetes in cotransfer with islet-infiltrating cells. Furthermore, CD62L
      expression is necessary for this disease-delaying effect of CD4(+)CD25(+) cells
      in vivo, but not for their suppressor function in vitro. We demonstrate that the
      CD4(+)CD25(+)CD62L(+) splenocytes express CCR7 at high levels and migrate toward
      secondary lymphoid tissue chemokine and ELC (macrophage-inflammatory protein
      3beta), lymphoid chemokines, whereas CD4(+)CD25(+)CD62L(-) splenocytes
      preferentially express CCR2, CCR4, and CXCR3 and migrate toward the corresponding
      inflammatory chemokines. These data demonstrate that CD4(+)CD25(+)CD62L(+), but
      not CD4(+)CD25(+)CD62L(-), splenocytes delay diabetes transfer, and that
      CD4(+)CD25(+) suppressor T cells are comprised of at least two subpopulations
      that behave differently in cotransfer in vivo and express distinct chemokine
      receptor and chemotactic response profiles despite demonstrating equivalent
      suppressor functions in vitro.

PMID- 12193714
TI  - TCR-independent CD30 signaling selectively induces IL-13 production via a TNF
      receptor-associated factor/p38 mitogen-activated protein kinase-dependent
      mechanism.
AB  - Initiation of T lymphocyte responses to most Ags requires concurrent stimulation
      through the TCR and costimulatory receptors such as CD28. Following initial
      activation, secondary receptors are up-regulated that can costimulate T cells in
      concert with TCR engagement. One such receptor is the TNFR family member CD30. In
      this study, we report that unlike CD28, ligation of CD30 on normal effector T
      cells induces IL-13 production in the absence of concurrent TCR engagement. TCR
      independent CD30-mediated IL-13 release correlated with activation of c-Jun N
      terminal kinase, p38 mitogen-activated protein kinase (MAPK), and NF-kappaB, and
      was completely inhibited by the expression of a TNFR-associated factor 2 (TRAF2)
      dominant-negative transgene (TRAF2.DN-Tg), but not by that of an I-kappaBalpha
      dominant-negative transgene. In parallel, expression of the TRAF2.DN-Tg
      selectively prevented the induction of c-Jun N-terminal kinase and p38 MAPK, but
      not that of NF-kappaB. Furthermore, IL-13 production was reduced in a dose
      dependent manner by the p38 MAPK inhibitor SB203580. Together, these results
      suggest that TCR-independent CD30-mediated production of IL-13 is triggered by
      association of CD30 with TRAF family members and subsequent activation of p38
      MAPK. Inasmuch as IL-13 can promote airway inflammation and cancer progression,
      production of IL-13 in a TCR-independent manner has important pathological
      implications in vivo.

PMID- 12193716
TI  - The human IL-2 gene promoter can assemble a positioned nucleosome that becomes
      remodeled upon T cell activation.
AB  - Controlled production of the cytokine IL-2 plays a key role in the mammalian
      immune system. Expression from the gene is tightly regulated with no detectable
      expression in resting T cells and a strong induction following T cell activation.
      The IL-2 proximal promoter (+1 to -300) contains many well-defined
      transcriptional activation elements that respond to T cell stimulation. To
      determine the role of chromatin structure in the regulation of interleukin-2 gene
      transcription, nucleosome assembly across the IL-2 promoter region was examined
      using in vitro chromatin reconstitution assays. The IL-2 promoter assembles a
      nucleosome that is both translationally and rotationally positioned, spanning
      some of the major functional control elements. The binding of transcription
      factors to these elements, with the exception of the architectural protein HMGA1,
      was occluded by the presence of the nucleosome. Analysis of the chromatin
      architecture of the IL-2 gene in Jurkat T cells provided evidence for the
      presence of a similarly positioned nucleosome in vivo. The region encompassed by
      this nucleosome becomes remodeled following activation of Jurkat T cells. These
      observations suggest that the presence of a positioned nucleosome across the IL-2
      proximal promoter may play an important role in maintaining an inactive gene in
      resting T cells and that remodeling of this nucleosome is important for gene
      activation.

PMID- 12193719
TI  - Cytokine coexpression during human Th1/Th2 cell differentiation: direct evidence
      for coordinated expression of Th2 cytokines.
AB  - We have developed an in vitro differentiation assay in which human naive CD4(+)
      cells are driven toward either the Th1 or Th2 phenotype. We have examined the
      interrelationships among the expression of IL-2, IL-4, IL-5, IL-10, IL-13, GM
      CSF, and IFN-gamma in individual cells using intracellular cytokine staining at
      various times during the differentiation process. We provide direct evidence that
      the Th2 cytokines IL-4, IL-5, and IL-13, unlike the other cytokines, are
      regulated by a coordinated mechanism. We also show that IL-10 is expressed by a
      different subset of cells that is prevalent at early stages of Th2
      differentiation, but then diminishes. Additionally we demonstrate that while
      naive cells can express IL-2 upon activation, they cannot express GM-CSF.
      Commitment to GM-CSF expression occurs during differentiation in a Th1/Th2 subset
      independent manner. Furthermore, we have examined the levels of GATA3, c-Maf, T
      bet, and Ets-related molecule during human Th1/Th2 differentiation and suggest
      that differences in the levels of these critical transcription factors are
      responsible for commitment toward the Th1 or Th2 lineage.

PMID- 12193718
TI  - The IgH locus of the channel catfish, Ictalurus punctatus, contains multiple
      constant region gene sequences: different genes encode heavy chains of membrane
      and secreted IgD.
AB  - The delta-chain of catfish IgD was initially characterized as a unique chimeric
      molecule containing a rearranged VDJ spliced to C micro 1, seven C domain
      encoding exons (delta1-delta7), and a transmembrane tail. The presence of cDNA
      forms showing splicing of delta7 to an exon encoding a secretory tail was
      interpreted to indicate that membrane (deltam) and secreted (deltas) forms were
      likely expressed from a single gene by alternative RNA processing. Subsequent
      cloning and sequence analyses have unexpectedly revealed the presence of three
      delta C region genes, each linked to a micro gene or pseudogene. The first
      (IGHD1) is located 1.6 kb 3' of the functional C micro (IGHM1). The second
      (IGHD3) is positioned immediately downstream of a pseudo C micro (IGHM3P),
      approximately 725 kb 5' of IGHM1. These two delta genes are highly similar in
      sequence and each contains a tandem duplication of delta2-delta3-delta4. However,
      IGHD1 has a terminal exon encoding the transmembrane region, whereas IGHD3 has a
      single terminal exon encoding a secreted tail. The occurrence of IGHD3
      immediately downstream of a micro pseudogene indicates that the putative deltas
      product may not be expressed as a chimeric micro delta molecule. Western blots
      and protein sequencing data indicate that an IGHD3-encoded protein is expressed
      in catfish serum. Thus, catfish deltam transcripts appear to originate from
      IGHD1, whereas deltas transcripts originate from IGHD3 rather than, as previously
      inferred, from a single expressed delta gene. The third delta (IGHD2) is
      associated with a pseudo C micro (IGHM2P); its presence is inferred by Southern
      blot analyses.

PMID- 12193717
TI  - High frequency of matrix attachment regions and cut-like protein x/CCAAT
      displacement protein and B cell regulator of IgH transcription binding sites
      flanking Ig V region genes.
AB  - A major component in controlling V(D)J recombination is differential
      accessibility through localized changes in chromatin structure. Attachment of DNA
      to the nuclear matrix via matrix attachment region (MAR) sequences, and
      interaction with MAR-binding proteins have been shown to alter chromatin
      conformation, promote histone acetylation, and influence gene transcription. In
      this study, the flanking regions of several human and mouse Ig V(H) and Ig Vkappa
      genes were analyzed extensively for the presence of MARs by in vitro matrix
      binding assay, and for interaction with the MAR-binding proteins cut-like protein
      x/CCAAT-displacement protein (Cux/CDP), B cell regulator of IgH transcription
      (Bright), and special AT-rich sequence-binding protein (SATB1) by EMSA. Cux/CDP
      and SATB1 are associated with repression, while Bright is an activator of Ig
      transcription. Binding sites were identified in the vicinity of all analyzed Ig V
      genes, and were also found flanking TCR Vbeta genes. We also show that the
      binding sites of the different factors do not always occur at MAR sequences. MAR
      sequences were also found within the Ig V loci at a much higher frequency than
      throughout the rest of the genome. Overall, the frequency and location of binding
      sites relative to the coding regions, and the strength of DNA-protein interaction
      showed much heterogeneity. Thus, variations in factor binding and MAR activity
      could potentially influence the extent of localized accessibility to V(D)J
      recombination and thus could play a role in unequal rearrangement of individual V
      genes. These sites could also contribute to effective transcription of Ig genes
      in mature and/or activated B cells, bringing both the promoter as well as the
      enhancer regions into close proximity at the nuclear matrix.

PMID- 12193720
TI  - RGS13 regulates germinal center B lymphocytes responsiveness to CXC chemokine
      ligand (CXCL)12 and CXCL13.
AB  - Normal lymphoid tissue development and function depend upon directed cell
      migration. Providing guideposts for cell movement and positioning within lymphoid
      tissues, chemokines signal through cell surface receptors that couple to
      heterotrimeric G proteins, which are in turn subject to regulation by regulator
      of G protein signaling (RGS) proteins. In this study, we report that germinal
      center B lymphocytes and thymic epithelial cells strongly express one of the RGS
      family members, RGS13. Located between Rgs1 and Rgs2, Rgs13 spans 42 kb on mouse
      chromosome 1. Rgs13 encodes a 157-aa protein that shares 82% amino acid identity
      with its 159-aa human counterpart. In situ hybridization with sense and antisense
      probes localized Rgs13 expression to the germinal center regions of mouse spleens
      and Peyer's patches and to the thymus medulla. Affinity-purified RGS13 Abs
      detected RGS13-expressing cells in the light zone of the germinal center. RGS13
      interacted with both Gialpha and Gqalpha and strongly impaired signaling through
      G(i)-linked signaling pathways, including signaling through the chemokine
      receptors CXCR4 and CXCR5. Prolonged CD40 signaling up-regulated RGS13 expression
      in human tonsil B lymphocytes. These results plus previous studies of RGS1
      indicate the germinal center B cells use two RGS proteins, RGS1 and RGS13, to
      regulate their responsiveness to chemokines.

PMID- 12193721
TI  - Identification of multiple novel epididymis-specific beta-defensin isoforms in
      humans and mice.
AB  - Defensins comprise a family of cationic antimicrobial peptides that are
      characterized by the presence of six conserved cysteine residues. We identified
      two novel human beta-defensin (hBD) isoforms by mining the public human genomic
      sequences. The predicted peptides conserve the six-cysteine motif identical with
      hBD-4, termed hBD-5 and hBD-6. We also evaluated the characteristics of the mouse
      homologs of hBD-5, hBD-6, and HE2beta1, termed mouse beta-defensin (mBD)-12, mBD
      11, and mouse EP2e (mEP2e). The mBD-12 synthetic peptide showed salt-dependent
      antimicrobial activity. We demonstrate the epididymis-specific expression pattern
      of hBD-5, hBD-6, mBD-11, mBD-12, and mEP2e. In situ hybridization revealed mBD
      11, mBD-12, and mEP2e expression in the columnar epithelium of the caput
      epididymis, contrasting with the predominant expression of mBD-3 in the capsule
      or septum of the whole epididymis. In addition, the regional specificity of mBD
      11, mBD-12, and mEP2e was somewhat overlapping, but not identical, in the caput
      epididymis, suggesting that specific regulation may work for each member of the
      beta-defensin family. Our findings indicated that multiple beta-defensin isoforms
      specifically and cooperatively contribute to the innate immunity of the
      urogenital system.

PMID- 12193722
TI  - Multiple Chlamydia pneumoniae antigens prime CD8+ Tc1 responses that inhibit
      intracellular growth of this vacuolar pathogen.
AB  - CD8(+) T cells play an essential role in immunity to Chlamydia pneumoniae (Cpn).
      However, the target Ags recognized by Cpn-specific CD8(+) T cells have not been
      identified, and the mechanisms by which this T cell subset contributes to
      protection remain unknown. In this work we demonstrate that Cpn infection primes
      a pathogen-specific CD8(+) T cell response in mice. Eighteen H-2(b) binding
      peptides representing sequences from 12 Cpn Ags sensitized target cells for MHC
      class I-restricted lysis by CD8(+) CTL generated from the spleens and lungs of
      infected mice. Peptide-specific IFN-gamma-secreting CD8(+) T cells were present
      in local and systemic compartments after primary infection, and these cells
      expanded after pathogen re-exposure. CD8(+) T cell lines to the 18 Cpn epitope
      bearing peptides were cytotoxic, displayed a memory phenotype, and secreted IFN
      gamma and TNF-alpha, but not IL-4. These CTL lines lysed Cpn-infected
      macrophages, and the lytic activity was inhibited by brefeldin A, indicating
      endogenous processing of CTL Ags. Finally, Cpn peptide-specific CD8(+) CTL
      suppressed chlamydial growth in vitro by direct lysis of infected cells and by
      secretion of IFN-gamma and other soluble factors. These studies provide
      information on the mechanisms by which CD8(+) CTL protect against Cpn, furnish
      the tools to investigate their possible role in immunopathology, and lay the
      foundation for future work to develop vaccines against acute and chronic Cpn
      infections.

PMID- 12193723
TI  - IL-18 levels and the outcome of innate immune response to lipopolysaccharide:
      importance of a positive feedback loop with caspase-1 in IL-18 expression.
AB  - LPS enhanced antibacterial host defenses (ABHD) when given at low (75 micro g)
      doses (16 of 19 mice survived 3x LD(50) Escherichia coli vs 3 of 19 LPS-naive
      mice; p = 0.0001), but induced lethal inflammation at high (500 micro g) doses (5
      of 5 died). Differences in the cytokine profiles induced by these LPS doses may
      provide insight into the mechanism(s) of transition from beneficial to lethal LPS
      responses. The 75 micro g LPS induced 5.9 +/- 0.9 ng/ml serum IL-18 at 8 h, which
      decreased to 2.3 +/- 0.4 ng/ml by 24 h, whereas 500 micro g LPS induced 11.1 +/-
      1.6 ng/ml serum IL-18 levels at 8 h, which increased until death. Compared with
      75 micro g, higher but sublethal (150 micro g) doses of LPS induced greater serum
      IL-18 levels and less effectively induced ABHD (3 of 8 survived). Reduction of
      serum IL-18 with neutralizing Ab improved the ABHD induced by 150 micro g, but
      reduced that produced by 75 micro g LPS, suggesting an optimal range of serum IL
      18 level was essential for efficient ABHD. Increased expression of caspase-1 mRNA
      in response to the higher IL-18 levels induced at the 150 and 500 micro g, but
      not at the 75 micro g doses of LPS may represent a positive feedback regulatory
      loop leading to sustained serum IL-18 levels. We conclude that the regulation of
      serum IL-18 expression is critical to the outcome of innate immune responses to
      LPS.

PMID- 12193725
TI  - IL-18 regulates intestinal mastocytosis and Th2 cytokine production independently
      of IFN-gamma during Trichinella spiralis infection.
AB  - Expulsion of the gastrointestinal nematode Trichinella spiralis is associated
      with pronounced mastocytosis mediated by a Th2-type response involving IL-4, IL
      10, and IL-13. Here we demonstrate that IL-18 is a key negative regulator of
      protective immune responses against T. spiralis in vivo. IL-18 knockout mice are
      highly resistant to T. spiralis infection, expel the worms rapidly and
      subsequently develop low levels of encysted muscle larvae. The increased speed of
      expulsion is correlated with high numbers of mucosal mast cells and an increase
      in IL-13 and IL-10 secretion. When normal mice were treated with rIL-18 in vivo,
      worm expulsion was notably delayed, and the development of mastocytosis and Th2
      cytokine production was significantly reduced. The treatment had no effect on
      intestinal eosinophilia or goblet cell hyperplasia but specifically inhibited the
      development of mastocytosis. Addition of rIL-18 to in vitro cultures of bone
      marrow-derived mast cells resulted in a significant reduction in cell yields as
      well as in the number of IL-4-secreting mast cells. In vivo treatment of T.
      spiralis-infected IFN-gamma knockout mice with rIL-18 demonstrated that the
      inhibitory effect of IL-18 on mastocytosis and Th2 cytokine secretion is
      independent of IFN-gamma. Hence, IL-18 plays a significant biological role as a
      negative regulator of intestinal mast cell responses and may promote the survival
      of intestinal parasites in vivo.

PMID- 12193724
TI  - Role of IL-12-independent and IL-12-dependent pathways in regulating generation
      of the IFN-gamma component of T cell responses to Salmonella typhimurium.
AB  - Clearance of facultative intracellular pathogens such as Salmonella requires IFN
      gamma from CD4 T cells. Mechanisms linking intracellular pathogen recognition
      with induction of IFN-gamma-producing T cells are still poorly understood. We
      show in this study that IL-12 is not required for commitment to the IFN-gamma
      producing T cell response in infection with Salmonella typhimurium, but is needed
      for its maintenance. The IL-12-independent signals required for commitment depend
      on events during the first hour of infection and are related to Ag presentation.
      Even transient attenuation of Ag presentation early during infection specifically
      abrogates the IFN-gamma component of the resulting CD4 T cell response. The IL-12
      needed for maintenance is also better induced by live rather than dead bacteria
      in vivo, and this difference is due to specific suppression of IL-12 induction by
      dead bacteria. Presence of exogenous IL-4 down-modulates IL-12 production by
      macrophages activated in vitro. Furthermore, macrophages from IL-4-null mice
      secrete high levels of both IL-12 and IL-18 in response to stimulation in vivo
      even with dead bacteria, but this does not lead to induction of IFN-gamma
      secreting T cells in response to immunization with dead S. typhimurium. Early IL
      4 is contributed by triggering of CD4 NK T cells by dead, but not live, bacteria.
      Thus, Ag presentation-related IL-12-independent events and IL-4-sensitive IL-12
      dependent events play crucial complementary roles in the generation of the IFN
      gamma-committed CD4 T cell component of the immune response in Salmonella
      infection.

PMID- 12193726
TI  - The bacterial superantigen streptococcal mitogenic exotoxin Z is the major
      immunoactive agent of Streptococcus pyogenes.
AB  - The gene encoding streptococcal mitogenic exotoxin Z (SMEZ) was disrupted in
      Streptococcus pyogenes. Despite the presence of other superantigen genes,
      mitogenic responses in human and murine HLA-DQ transgenic cells were abrogated
      when cells were stimulated with supernatant from the smez(-) mutant compared with
      the parent strain. Remarkably, disruption of smez led to a complete inability to
      elicit cytokine production (TNF-alpha, lymphotoxin-alpha, IFN-gamma, IL-1 and -8)
      from human cells, when cocultured with streptococcal supernatants. The potent
      effects of SMEZ were apparent even though transcription and expression of SMEZ
      were barely detectable. Human Vbeta8(+) T cell proliferation in response to S.
      pyogenes was SMEZ-dependent. Cells from HLA-DQ8 transgenic mice were 3 logs more
      sensitive to SMEZ-13 than cells from HLA-DR1 transgenic or wild-type mice. In the
      mouse, SMEZ targeted the human Vbeta8(+) TCR homologue, murine Vbeta11, at the
      expense of other TCR T cell subsets. Expression of SMEZ did not affect bacterial
      clearance or survival from peritoneal streptococcal infection in HLA-DQ8 mice,
      though effects of SMEZ on pharyngeal infection are unknown. Infection did lead to
      a rise in Vbeta11(+) T cells in the spleen which was partly reversed by
      disruption of the smez gene. Most strikingly, a clear rise in murine Vbeta4(+)
      cells was seen in mice infected with the smez(-) mutant S. pyogenes strain,
      indicating a potential role for SMEZ as a repressor of cognate anti-streptococcal
      responses.

PMID- 12193728
TI  - Vitamin K-dependent protein S localizing complement regulator C4b-binding protein
      to the surface of apoptotic cells.
AB  - Apoptosis is characterized by a lack of inflammatory reaction in surrounding
      tissues, suggesting local control of complement activation. During the initial
      stage of apoptosis, cells expose negatively charged phospholipid
      phosphatidylserine on their surfaces. The vitamin K-dependent protein S has a
      high affinity for this type of phospholipid. In human plasma, 60-70% of protein S
      circulates in complex with C4b-binding protein (C4BP). The reason why protein S
      and C4BP form a high-affinity complex in plasma is not known. However, C4BP is an
      important regulator of the classical pathway of the complement system where it
      acts as a cofactor in degradation of complement protein C4b. Using Jurkat cells
      as a model system for apoptosis, we now show protein S to bind to apoptotic
      cells. We further demonstrate protein S-mediated binding of C4BP to apoptotic
      cells. Binding of the C4BP-protein S complex to apoptotic cells was calcium
      dependent and could be blocked with Abs directed against the phospholipid-binding
      domain in protein S. Annexin V, which binds to exposed phosphatidylserine on the
      apoptotic cell surface, could inhibit the binding of protein S. The C4BP that was
      bound via protein S to the apoptotic cells was able to interact with the
      complement protein C4b, supporting a physiological role of the C4BP/protein S
      complex in regulation of complement on the surface of apoptotic cells.

PMID- 12193730
TI  - Complement activates the c-Jun N-terminal kinase/stress-activated protein kinase
      in glomerular epithelial cells.
AB  - In the rat passive Heymann nephritis model of membranous nephropathy, complement
      C5b-9 induces sublethal glomerular epithelial cell (GEC) injury and proteinuria.
      C5b-9 activates cytosolic phospholipase A(2) (cPLA(2)), and products of cPLA(2)
      mediated phospholipid hydrolysis modulate GEC injury and proteinuria. In the
      present study, we demonstrate that C5b-9 activates c-Jun N-terminal kinase (JNK)
      in cultured rat GECs and that JNK activity is increased in glomeruli isolated
      from proteinuric rats with passive Heymann nephritis, as compared with control
      rats. Stable overexpression of cPLA(2) in GECs amplified complement-induced
      release of arachidonic acid (AA) and JNK activity, as compared with neo (control)
      GECs. Activation of JNK was not affected by indomethacin. Incubation of GECs with
      complement stimulated production of superoxide, and pretreatment with the
      antioxidants, N-acetylcysteine, glutathione, and alpha-tocopherol as well as with
      diphenylene iodonium, an inhibitor of the NADPH oxidase, inhibited complement
      induced JNK activation. Conversely, H(2)O(2) activated JNK, whereas exogenously
      added AA stimulated both superoxide production and JNK activity. Overexpression
      of a dominant-inhibitory JNK mutant or treatment with diphenylene iodonium
      exacerbated complement-dependent GEC injury. Thus, activation of cPLA(2) and
      release of AA facilitate complement-induced JNK activation. AA may activate the
      NADPH oxidase, leading to production of reactive oxygen species, which in turn
      mediate the activation of JNK. The functional role of JNK activation is to limit
      or protect GECs from complement attack.

PMID- 12193729
TI  - Inhibition of NF-kappa B activity by a membrane-transducing mutant of I kappa B
      alpha.
AB  - The transcription factor NF-kappaB is regulated by the IkappaB family of
      proteins. The nonphosphorylatable, nondegradable superrepressor IkappaBalpha
      (srIkappaBalpha) mutant is a potent inhibitor of NF-kappaB activity when
      expressed in cells. We generated a form of srIkappaBalpha in which its N terminus
      is fused to the protein transduction domain of HIV TAT (TAT-srIkappaBalpha).
      Purified TAT-srIkappaBalpha protein rapidly and efficiently entered HeLa or
      Jurkat T cells. TAT-srIkappaBalpha, when exogenously added to HeLa cells,
      inhibited in a dose-dependent manner TNF-alpha- or IL-1beta-induced NF-kappaB
      activation and binding of NF-kappaB to its consensus DNA sequence. TAT
      srIkappaBalpha was coimmunoprecipitated with the p65 subunit of NF-kappaB, and
      this interaction was resistant to stimulation with IL-1beta. Therefore, TAT
      srIkappaBalpha-mediated inhibition could result from its nonreversible binding
      and sequestration of endogenous NF-kappaB. In contrast, exogenously added TAT
      srIkappaBalpha did not inhibit IL-1beta-induced activation of extracellular
      signal-regulated kinase, c-Jun N-terminal kinase, or p38 mitogen-activated
      protein kinases or the phosphorylation and degradation of endogenous
      IkappaBalpha. These results identify a novel way for direct regulation of NF
      kappaB activity in diverse cell types that may be useful for therapeutic
      purposes.

PMID- 12193731
TI  - Platelet-derived chemokines CXC chemokine ligand (CXCL)7, connective tissue
      activating peptide III, and CXCL4 differentially affect and cross-regulate
      neutrophil adhesion and transendothelial migration.
AB  - In this study, we have examined the major platelet-derived CXC chemokines
      connective tissue-activating peptide III (CTAP-III), its truncation product
      neutrophil-activating peptide 2 (CXC chemokine ligand 7 (CXCL7)), as well as the
      structurally related platelet factor 4 (CXCL4) for their impact on neutrophil
      adhesion to and transmigration through unstimulated vascular endothelium. Using
      monolayers of cultured HUVEC, we found all three chemokines to promote neutrophil
      adhesion, while only CXCL7 induced transmigration. Induction of cell adhesion
      following exposure to CTAP-III, a molecule to date described to lack neutrophil
      stimulating capacity, depended on proteolytical conversion of the inactive
      chemokine into CXCL7 by neutrophils. This was evident from experiments in which
      inhibition of the CTAP-III-processing protease and simultaneous blockade of the
      CXCL7 high affinity receptor CXCR-2 led to complete abrogation of CTAP-III
      mediated neutrophil adhesion. CXCL4 at substimulatory dosages modulated CTAP-III-
      as well as CXCL7-induced adhesion. Although cell adhesion following exposure to
      CTAP-III was drastically reduced, CXCL7-mediated adhesion underwent significant
      enhancement. Transendothelial migration of neutrophils in response to CXCL7 or IL
      8 (CXCL8) was subject to modulation by CTAP-III, but not CXCL4, as seen by
      drastic desensitization of the migratory response of neutrophils pre-exposed to
      CTAP-III, which was paralleled by selective down-modulation of CXCR-2. Altogether
      our results demonstrate that there exist multiple interactions between platelet
      derived chemokines in the regulation of neutrophil adhesion and transendothelial
      migration.

PMID- 12193727
TI  - Subset-specific reductions in lung lymphocyte accumulation following
      intratracheal antigen challenge in endothelial selectin-deficient mice.
AB  - We previously demonstrated induction and expression of CD62E and CD62P in the
      lungs of mice primed and then challenged with intratracheal (i.t.) SRBC. The
      current study examined accumulation of endogenous lymphocytes in the lungs of
      endothelial E- and P-selectin-deficient (E(-)P(-)) mice after i.t. SRBC
      challenge. Compared with syngeneic wild-type (wt) mice, E(-)P(-) mice showed an
      85-95% decrease in CD8(+) T cells and B cells in the lungs at both early and late
      time points. In contrast, CD4(+) T cell accumulation was reduced by approximately
      60% early, but equivalent to wt levels later. Surprisingly, many gammadelta T
      cells were found in lungs and blood of E(-)P(-) mice but were undetectable in the
      lungs and blood of wt mice. Absolute numbers of peripheral blood CD4, CD8, and B
      lymphocytes in E(-)P(-) mice equaled or exceeded the levels in wt mice,
      particularly after challenge. Trafficking studies using alphabeta T lymphoblasts
      confirmed that the recruitment of circulating cells after challenge was markedly
      reduced in E(-)P(-) mice. Furthermore, Ag priming occurred normally in both the
      selectin-deficient and wt mice, because primed lymphocytes from both groups
      transferred Ag sensitivity into naive wt mice. Lung production of mRNA for six CC
      and two CXC chemokines after challenge was equivalent by RT-PCR analysis in wt
      and E(-)P(-) mice. Therefore, reduced lung accumulation of alphabeta T cells and
      B cells in E(-)P(-) mice did not result from reduced delivery of circulating
      lymphocytes to the lungs, unsuccessful Ag priming, or defective pulmonary
      chemokine production. Selectin-dependent lymphocyte recruitment into the lungs
      following i.t.-SRBC challenge is subset specific and time dependent.

PMID- 12193732
TI  - Lipopolysaccharide signals an endothelial apoptosis pathway through TNF receptor
      associated factor 6-mediated activation of c-Jun NH2-terminal kinase.
AB  - Inflammatory mediators such as TNF and bacterial LPS do not cause significant
      apoptosis of endothelial cells unless the expression of cytoprotective genes is
      blocked. In the case of TNF, the transcription factor NF-kappaB conveys an
      important survival signal. In contrast, even though LPS can also activate NF
      kappaB, this signal is dispensable for LPS-inducible cytoprotective activity. LPS
      intracellular signals are transmitted through a member of the Toll-like receptor
      family, TLR4. This family of receptors transduces signals through a downstream
      molecule, TNFR-associated factor 6 (TRAF6). In this study, we demonstrate that
      the C-terminal fragment of TRAF6 (TRAF6-C) inhibits LPS-induced NF-kappaB nuclear
      translocation and c-Jun NH(2)-terminal kinase (JNK) activation in endothelial
      cells. In contrast, LPS activation of p38 kinase is not inhibited by TRAF6-C.
      TRAF6-C also inhibits LPS-initiated endothelial apoptosis, but potentiates TNF
      induced apoptosis. LPS-induced loss of mitochondrial transmembrane potential,
      cytochrome c release, and caspase activation are all blocked by TRAF6-C. We
      demonstrate that TRAF6 signals apoptosis via JNK activation, since inhibition of
      JNK activation using a dominant-negative mutant also inhibits apoptosis. JNK
      inhibition blocks caspase activation, but the reverse is not true. Hence, JNK
      activation lies upstream of caspase activation in response to LPS stimulation.

PMID- 12193733
TI  - Activation of peroxisome proliferator-activated receptor gamma by nitric oxide in
      monocytes/macrophages down-regulates p47phox and attenuates the respiratory
      burst.
AB  - NO appears as an important determinant in auto and paracrine macrophage function.
      We hypothesized that NO switches monocyte/macrophage function from a pro- to an
      anti-inflammatory phenotype by activating anti-inflammatory properties of the
      peroxisome proliferator-activated receptor (PPAR)gamma. NO-releasing compounds
      (100 micro M S-nitrosoglutathione or 50 micro M spermine-NONOate) as well as
      inducible NO synthase induction provoked activation of PPARgamma. This was proven
      by EMSAs, with the notion that supershift analysis pointed to the involvement of
      PPARgamma. PCR analysis ruled out induction of PPARgamma mRNA as a result of NO
      supplementation. Reporter assays, with a construct containing a triple PPAR
      response element in front of a thymidine kinase minimal promoter driving the
      luciferase gene, were positive in response to NO delivery. DNA binding capacity
      as well as the transactivating capability of PPARgamma were attenuated by
      addition of the antioxidant N-acetyl-cysteine or in the presence of the NO
      scavenger 2-phenyl-4,4,5,6-tetramethyl-imidazoline-1-oxyl 3-oxide. Having
      established that NO but not lipophilic cyclic GMP analogs activated PPARgamma, we
      verified potential anti-inflammatory consequences. The oxidative burst of
      macrophages, evoked by phorbol ester, was attenuated in association with NO
      elicited PPARgamma activation. A cause-effect relationship was demonstrated when
      PPAR response element decoy oligonucleotides, supplied in front of NO delivery,
      allowed to regain an oxidative response. PPARgamma-mediated down-regulation of
      p47 phagocyte oxidase, a component of the NAD(P)H oxidase system, was identified
      as one molecular mechanism causing inhibition of superoxide radical formation. We
      conclude that NO participates in controlling the pro- vs anti-inflammatory
      phenotype of macrophages by modulating PPARgamma.

PMID- 12193734
TI  - Complement factor B gene regulation: synergistic effects of TNF-alpha and IFN
      gamma in macrophages.
AB  - Complement factor B (Bf) plays an important role in activating the alternative
      complement pathway. The inflammatory cytokines, in particular TNF-alpha and IFN
      gamma, are critical in the regulation of Bf gene expression in macrophages. In
      this study, we investigated the mechanisms of Bf gene regulation by TNF-alpha and
      IFN-gamma in murine macrophages. Northern analysis revealed that Bf mRNA
      expression was synergistically up-regulated by TNF-alpha and IFN-gamma in MH-S
      cells. Truncations of the 5' Bf promoter identified a region between -556 and 
      282 bp that mediated TNF-alpha responsiveness as well as the synergistic effect
      of TNF-alpha and IFN-gamma on Bf expression. Site-directed mutagenesis of a NF
      kappaB-binding element in this region (-433 to -423 bp) abrogated TNF-alpha
      responsiveness and decreased the synergistic effect of TNF-alpha and IFN-gamma on
      Bf expression. EMSAs revealed nuclear protein binding to this NF-kappaB cis
      binding element on TNF-alpha stimulation. Supershift analysis revealed that both
      p50 and p65 proteins contribute to induction of Bf by TNF-alpha. An I-kappaB
      dominant negative mutant blocked Bf induction by TNF-alpha and reduced the
      synergistic induction by TNF-alpha and IFN-gamma. In addition, the proteasome
      inhibitor MG132, which blocks NF-kappaB induction, blocked TNF-alpha-induced Bf
      promoter activity and the synergistic induction of Bf promoter activity by TNF
      alpha and IFN-gamma. LPS was found to induce Bf promoter activity through the
      same NF-kappaB cis-binding site. These findings suggest that a NF-kappaB cis
      binding site between -433 and -423 bp is required for TNF-alpha responsiveness
      and for TNF-alpha- and IFN-gamma-stimulated synergistic responsiveness of the Bf
      gene.

PMID- 12193735
TI  - The Pseudomonas autoinducer N-(3-oxododecanoyl) homoserine lactone induces
      cyclooxygenase-2 and prostaglandin E2 production in human lung fibroblasts:
      implications for inflammation.
AB  - Pseudomonas aeruginosa causes lethal lung infections in immunocompromised
      individuals such as those with cystic fibrosis. The lethality of these infections
      is directly associated with inflammation and lung tissue destruction. P.
      aeruginosa produces several acylated homoserine lactones (AHL) that are important
      in the regulation of bacterial virulence factors. Little is known about the
      effects of AHLs on human cells. In this work we report that the AHL N-(3
      oxododecanoyl) homoserine lactone (3O-C(12)-HSL) from P. aeruginosa induces
      cyclooxygenase (Cox)-2, a seminal proinflammatory enzyme. When primary normal
      human lung fibroblasts were exposed to 3O-C(12)-HSL, an 8-fold induction in mRNA
      and a 35-fold increase in protein for Cox-2 were observed. In contrast, there was
      no substantial change in the expression of Cox-1. We also demonstrated that the
      induction of Cox-2 was regulated by 3O-C(12)-HSL activation of the transcription
      factor NF-kappaB. 3O-C(12)-HSL also stimulated an increase in the newly
      discovered inducible membrane-associated PGE synthase but had no effect on the
      expression of the cytosolic PGE synthase. We also demonstrate that 3O-C(12)-HSL
      stimulated the production of PGE(2). PGE(2) is known to induce mucus secretion,
      vasodilation, and edema, and acts as an immunomodulatory lipid mediator. We
      propose that 3O-C(12)-HSL induction of Cox-2, membrane-associated PGE synthase,
      and PGE(2) likely contributes to the inflammation and lung pathology induced by
      P. aeruginosa infections in the lung. These studies further reinforce the concept
      that bacterial AHLs not only regulate bacterial virulence but also stimulate the
      activities of eukaryotic cells important for inflammation and immune defenses.

PMID- 12193736
TI  - The role of matrix metalloproteinase-2 and matrix metalloproteinase-9 in antibody
      induced arthritis.
AB  - Matrix metalloproteinases (MMPs) are a large group of enzymes responsible for
      matrix degradation. Among them, the family of gelatinases (MMP-2/gelatinase A and
      MMP-9/gelatinase B) is overproduced in the joints of patients with rheumatoid
      arthritis. Because of their degradative effects on the extracellular matrix,
      gelatinases have been believed to play an important role in progression and
      cartilage degradation in this disease, although their precise roles are yet to be
      defined. To clarify these roles, we investigated the development of Ab-induced
      arthritis, one of the murine models of rheumatoid arthritis, in MMP-2 or MMP-9
      knockout (KO) mice. Surprisingly, the MMP-2 KO mice exhibited severe clinical and
      histologic arthritis than wild-type mice. The MMP-9 KO mice displayed milder
      arthritis. Recovery from exacerbated arthritis in the MMP-2 KO mice was possible
      by injection of wild-type fibroblasts. These results indicated a suppressive role
      of MMP-2 and a pivotal role of MMP-9 in the development of inflammatory joint
      disease.

PMID- 12193737
TI  - Pathophysiological contributions of fucosyltransferases in renal ischemia
      reperfusion injury.
AB  - Ischemia reperfusion injury (IRI) is a major cause of delayed graft function.
      Recent studies have shown that selectins play an important role in IRI. Selectins
      bind to sialylated and fucosylated sLe(x) receptors, and two enzymes,
      fucosyltransferase IV (FucT-IV) and VII (FucT-VII), are important in the function
      of these receptors. We hypothesized that fucosyltransferase (FucT) enzymes were
      important pathophysiologic mediators of renal IRI. We therefore evaluated renal
      IRI in mice deficient in FucT-IV, FucT-VII, and both FucT-IV and FucT-VII and
      compared their renal function, tubular injury, selectin ligand expression, and
      neutrophil infiltration to those in wild-type control mice. Bilateral 30-min
      renal IRI was performed, and the results demonstrated that mice deficient in both
      FucT-IV/FucT-VII were significantly protected from renal IRI at 24 and 48 h
      compared with wild-type control mice. FucT-IV-deficient mice showed only modest
      protection from renal injury at 24 h. However, FucT-VII-deficient mice had
      similar injury as wild-type mice. Histological analysis of kidney tissue
      postischemia revealed that mice deficient in both FucT-IV and FucT-VII had
      significantly reduced tubular injury compared with wild-type mice. Selectin
      ligand expression increased postischemia in wild-type, but not FucT-IV/FucT-VII
      deficient, mice. Neutrophil infiltration in postischemic kidneys of FucT-IV/FucT
      VII-deficient mice was also attenuated. These data demonstrate that
      fucosyltransferases are important in the pathogenesis of renal IRI and are
      potential therapeutic targets.

PMID- 12193738
TI  - A profibrotic function of IL-12p40 in experimental pulmonary fibrosis.
AB  - The p40 subunit of IL-12 (IL-12p40), but not the heterodimeric form IL-12p70, is
      secreted during the development of silica-induced lung fibrosis in C57BL/6 mice.
      To delineate the contribution of IL-12p40 to the lung inflammatory and fibrotic
      processes, we compared the pulmonary responses with silica particles of IL-12p35
      deficient mice (IL-12p35(-/-), able to produce IL-12p40) and IL-12p40-deficient
      mice (IL-12p40(-/-)). IL-12p35(-/-) and IL-12p40(-/-) animals developed
      strikingly contrasting responses to silica in comparison with wild-type C57BL/6
      mice. Although the IL-12p40(-/-) mice exhibited limited inflammatory and fibrotic
      reactions, the IL-12p35(-/-) mice presented a robust and well-developed pulmonary
      inflammation and fibrosis. Furthermore, the silica-induced increase in lung IL
      12p40 content was significantly higher in IL-12p35(-/-) mice than in wild-type
      controls, and was associated with extensive lung fibrosis and pulmonary
      macrophage infiltration. The contrasting responses observed between these two IL
      12 subunit-deficient murine strains were not accompanied by a strict type 1 or
      type 2 polarization as estimated by the measurements of lung IFN-gamma/IgG2a and
      IL-4/IgG1 content. In vitro proliferation, type I collagen expression, as well as
      myofibroblast differentiation of purified pulmonary fibroblasts were not affected
      by treatment with exogenous rIL-12p40. In vivo, supplementation with rIL-12p40
      restored the impaired pulmonary fibrotic response and macrophage accumulation in
      silica-treated IL-12p40(-/-) mice, and also promoted fibrosis and macrophage
      influx in wild-type mice. Together, our data suggest that IL-12p40 plays an
      important role in silica-induced pulmonary inflammation and fibrosis, possibly by
      exacerbating macrophage recruitment.

PMID- 12193739
TI  - Tryptase activates the mitogen-activated protein kinase/activator protein-1
      pathway in human peripheral blood eosinophils, causing cytokine production and
      release.
AB  - We have previously shown that mast cells enhance eosinophil survival and
      activation. In this study we further characterized mast cell activity toward
      eosinophils. Sonicate of both rat peritoneal mast cells and the human mast cell
      line 1 (HMC-1) induced a concentration-dependent IL-6 and IL-8 release from human
      peripheral blood eosinophils (ELISA). HMC-1-induced IL-8 release was
      significantly reduced by the tryptase inhibitors GW-45 and GW-58 (90 and 87%,
      respectively, at an optimal concentration) but not by anti-stem cell factor, anti
      TNF-alpha, or anti-IFN-gamma neutralizing Abs or by the antihistamine drugs
      pyrilamine and cimetidine. In a manner similar to HMC-1, human recombinant
      tryptase induced the expression of mRNA for IL-8 (RT-PCR) and caused IL-8 release
      from the eosinophils. Addition of cycloheximide, actinomycin D, dexamethasone, PD
      98059, curcumin, or SB 202190 completely inhibited the tryptase-induced IL-6 and
      IL-8 release. In contrast, cyclosporin A had no effect on tryptase-induced IL-8
      release. Tryptase caused phosphorylation of extracellular signal-regulated
      kinases 1 and 2, c-Jun N-terminal kinases 1 and 2, and p38 (Western blot).
      Tryptase also induced the translocation of c-Jun from the cytosol to the nucleus
      (confocal microscopy) and enhanced AP-1 binding activity to the DNA (EMSA).
      Eosinophils were found to express proteinase-activated receptor 2 (FACS). When
      eosinophils were incubated with tryptase in the presence of anti-proteinase
      activated receptor 2 antagonist Abs a significant decrease in the IL-6 and IL-8
      release occurred. In summary, we have demonstrated that the preformed mast cell
      mediator tryptase induces cytokine production and release in human peripheral
      blood eosinophils by the mitogen-activated protein kinase/AP-1 pathway.

PMID- 12193740
TI  - Blockade of focal clustering and active conformation in beta 2-integrin-mediated
      adhesion of eosinophils to intercellular adhesion molecule-1 caused by
      transduction of HIV TAT-dominant negative Ras.
AB  - We transduced dominant negative (dn) HIV TAT-Ras protein into mature human
      eosinophils to determine the signaling pathways and mechanism involved in
      integrin-mediated adhesion caused by cytokine, chemokine, and chemoattractant
      stimulation. Transduction of TAT-dnRas into nondividing eosinophils inhibited
      endogenous Ras activation and extracellular signal-regulated kinase (ERK)
      phosphorylation caused by IL-5, eotaxin-1, and fMLP. IL-5, eotaxin-1, or fMLP
      caused 1) change of Mac-1 to its active conformation and 2) focal clustering of
      Mac-1 on the eosinophil surface. TAT-dnRas or PD98059, a pharmacological mitogen
      activated protein/ERK kinase inhibitor, blocked both focal surface clustering of
      Mac-1 and the change to active conformational structure of this integrin assessed
      by the mAb CBRM1/5, which binds the activation epitope. Eosinophil adhesion to
      the endothelial ligand ICAM-1 was correspondingly blocked by TAT-dnRas and
      PD98059. As a further control, we used PMA, which activates ERK phosphorylation
      by postmembrane receptor induction of protein kinase C, a mechanism which
      bypasses Ras. Neither TAT-dnRas nor PD98059 blocked eosinophil adhesion to ICAM
      1, up-regulation of CBRM1/5, or focal surface clustering of Mac-1 caused by PMA.
      In contrast to beta(2)-integrin adhesion, neither TAT-dnRas nor PD98059 blocked
      the eosinophil adhesion to VCAM-1. Thus, a substantially different signaling
      mechanism was identified for beta(1)-integrin adhesion. We conclude that H-Ras
      mediated activation of ERK is critical for beta(2)-integrin adhesion and that Ras
      protein functions as the common regulator for cytokine-, chemokine-, and G
      protein-coupled receptors in human eosinophils.

PMID- 12193741
TI  - Prevention of chronic rejection in murine cardiac allografts: a comparison of
      chimerism- and nonchimerism-inducing costimulation blockade-based tolerance
      induction regimens.
AB  - We have previously described a nonirradiation-based regimen combining
      costimulation blockade, busulfan, and donor bone marrow cells that promotes
      stable, high level chimerism, deletion of donor-reactive T cells, and indefinite
      survival of skin allografts in mice. The purpose of the current study is to
      determine the efficacy of this tolerance regimen in preventing acute and chronic
      rejection in a vascularized heart graft model and to compare this regimen with
      other putative tolerance protocols. Mice receiving costimulation blockade (CTLA4
      Ig and anti-CD40 ligand) alone or in combination with donor cells enjoyed
      markedly prolonged heart graft survival and initially preserved histological
      structure. However, tolerance was not achieved, as evidenced by the eventual
      onset of chronic rejection characterized by obliterative vasculopathy and the
      rejection of secondary skin grafts. In contrast, following treatment with
      costimulation blockade, busulfan, and bone marrow, heart grafts survived
      indefinitely without detectable signs of chronic rejection or structural damage,
      even 100 days after placement of a secondary donor skin graft. We detected
      multilineage chimerism in peripheral blood, spleen, lymph nodes, and thymus, and
      peripheral deletion of donor-reactive cells was complete by day 90. These
      findings indicate that only the CD40/CD28 blockade chimerism induction regimen
      prevents both acute and chronic rejection of vascularized organ transplants.
      Further testing of these strategies in a preclinical large animal model is
      warranted.

PMID- 12193742
TI  - Targeting the function of IFN-gamma-inducible protein 10 suppresses ongoing
      adjuvant arthritis.
AB  - IFN-gamma-inducible protein 10 (IP-10) is a CXC chemokine that is thought to
      manifest a proinflammatory role because it stimulates the directional migration
      of activated T cells, particularly Th1 cells. It is an open question whether this
      chemokine is also directly involved in T cell polarization. We show here that
      during the course of adjuvant-induced arthritis the immune system mounts a
      notable Ab titer against self-IP-10. Upon the administration of naked DNA
      encoding IP-10, this titer rapidly accelerates to provide protective immunity.
      Self-specific Ab to IP-10 developed in protected animals, as well as neutralizing
      Ab to IP-10 that we have generated in rabbits, could inhibit leukocyte migration,
      alter the in vivo and in vitro Th1/Th2 balance toward low IFN-gamma, low TNF
      alpha, high IL-4-producing T cells, and adoptively transfer disease suppression.
      This not only demonstrates the pivotal role of this chemokine in T cell
      polarization during experimentally induced arthritis but also suggests a
      practical way to interfere in the regulation of disease to provide protective
      immunity. From the basic science perspective, this study challenges the paradigm
      of in vivo redundancy. After all, we did not neutralize the activity of other
      chemokines that bind CXCR3 (i.e., macrophage-induced gene and IFN-inducible T
      cell alpha chemoattractant) and yet significantly blocked not only adjuvant
      induced arthritis but also the in vivo competence to mount delayed-type
      hypersensitivity.

PMID- 12193743
TI  - The major murine systemic lupus erythematosus susceptibility locus Sle1 results
      in abnormal functions of both B and T cells.
AB  - Sle1 is a major susceptibility locus in the NZM2410 murine model of systemic
      lupus erythematosus. When isolated on a C57BL/6 background in the B6.Sle1
      congenic strain, Sle1 results in the production of high levels of anti-chromatin
      IgG Abs, histone-specific T cells, and increased B and T cell activation. We have
      shown by mixed bone marrow chimeras with allotypic markers that Sle1 is expressed
      in B cells. Using the same technique, we now show that it is also expressed in T
      cells. To assess whether Sle1 results in intrinsic defects in B or T cells, we
      have bred the muMT and Tcralpha(-/-) mutations onto B6.Sle1 resulting in the
      absence of circulating B cells and alphabeta T cells in B6.Sle1.muMT and
      B6.Sle1.Tcralpha(-/-), respectively. The immune phenotypes in these two strains
      were compared with that of B6.Sle1 and B6.muMT or B6.Tcralpha(-/-). Sle1
      expressing B cells broke tolerance to chromatin in the absence of T cells, as
      shown by high levels of anti-ssDNA IgM Abs in B6.Sle1.Tcralpha(-/-) mice, and had
      an increased expression of activation markers. Conversely, increased expression
      of activation markers and increased cytokine production were observed in Sle1
      expressing T cells in the absence of B cells in B6.Sle1.muMT mice. However, the
      production of IgG antinuclear Abs required the presence of both T and B cells.
      These experiments showed that Sle1 expression results in both B and T cells
      intrinsic defects and demonstrate that the documented involvement of each cell
      compartment in the production of anti-chromatin Abs corresponds to genetic
      defects rather than bystander effects.

PMID- 12193744
TI  - Translocation of an intracellular antigen to the surface of medullary breast
      cancer cells early in apoptosis allows for an antigen-driven antibody response
      elicited by tumor-infiltrating B cells.
AB  - Tumor-infiltrating lymphoplasmacytic cells are a key feature of medullary
      carcinoma of the breast (MCB), a distinct subtype of human breast cancer that,
      despite cytologically anaplastic characteristics, has a more favorable prognosis
      than other types of breast cancer. Since it has been proposed that the improved
      clinical outcome is due at least in part to the presence of a prominent
      lymphoplasmacytic cell infiltrate in the tumor stroma, we recently examined the
      tumor-infiltrating B cell response in MCB and showed that it is oligoclonal and
      directed against an intracellular protein translocated to the cell surface upon
      MCB cell apoptosis. Human Abs cloned from MCB lymphoplasmacytic infiltrate
      derived phage display libraries and reflecting the dominant part of the response
      were used to identify the target Ag as actin. Here, we have characterized in
      detail the cloned human IgG Abs and the translocation process of actin to the
      cell surface of apoptotic MCB cells. Our analysis shows that the cloned Abs bind
      specifically and with high affinity to actin, as determined by ELISA and surface
      plasmon resonance. Sequence analysis revealed that the Abs are highly somatically
      mutated, with high replacement to silent ratios, indicative of an Ag-driven,
      affinity-matured response. Interestingly, the tumor-infiltrating B cells in half
      the MCB patients mainly exhibited an IgG2 response, while IgG1 dominated in the
      others. To gain insight to the molecular events that may elicit such an Ab
      response, we examined the translocation of actin to the cell surface of apoptotic
      MCB cells using flow cytometry and laser scanning cytometry. Our results show
      that actin becomes exposed on the cell surface of a large proportion of apoptotic
      MCB cells as an early apoptotic event. We propose that the Ab response against
      actin produced by tumor-infiltrating B lymphoplasmacytic cells is Ag-driven,
      affinity-matured, and elicited due to the increased rate of apoptosis occurring
      within the MCB tumor that facilitates the translocation and proteolytic
      fragmentation of intracellular proteins.

PMID- 12193745
TI  - Eotaxin (CCL11) and eotaxin-2 (CCL24) induce recruitment of eosinophils,
      basophils, neutrophils, and macrophages as well as features of early- and late
      phase allergic reactions following cutaneous injection in human atopic and
      nonatopic volunteers.
AB  - Eotaxin and eotaxin-2, acting through CCR3, are potent eosinophil
      chemoattractants both in vitro and in animal models. In this study we examined
      the capacity of eotaxin and eotaxin-2 to recruit eosinophils and other
      inflammatory cells in vivo in human atopic and nonatopic skin. Skin biopsies
      taken after intradermal injection of eotaxin and eotaxin-2 were examined by
      immunohistochemistry. Allergen- and diluent-challenged sites were used as
      positive and negative controls. Eotaxin and eotaxin-2 produced a dose- and time
      dependent local eosinophilia of comparable intensity in both atopic and nonatopic
      individuals. This was associated with an acute wheal and flare response at the
      site of injection and development of a cutaneous late phase reaction in a
      proportion of subjects. There was an accompanying decrease in mast cell numbers.
      Both chemokines also induced the accumulation of basophils and an unexpected
      early infiltration of neutrophils. Macrophages were prominent at the 24-h point.
      Although there was surface CCR3 expression on neutrophils in whole blood, we were
      unable to demonstrate any functional neutrophil responses to eotaxin in vitro.
      Thus, intradermal injection of eotaxin and eotaxin-2 in humans induced
      infiltration of eosinophils and other inflammatory cells as well as changes
      consistent with CC chemokine-induced mast cell degranulation.

PMID- 12193746
TI  - Functional activation of myelin-specific T cells by virus-induced molecular
      mimicry.
AB  - Molecular mimicry is the process by which T cells activated in response to
      determinants on an infecting microorganism cross-react with self epitopes,
      leading to an autoimmune disease. Normally, infection of SJL/J mice with the BeAn
      strain of Theiler's murine encephalomyelitis virus (TMEV) results in a persistent
      CNS infection, leading to a chronic progressive, CD4(+) T cell-mediated
      demyelinating disease. Myelin damage is initiated by T cell responses to virus
      persisting in CNS APCs, and progressive demyelinating disease (50 days
      postinfection) is perpetuated by myelin epitope-specific CD4(+) T cells activated
      by epitope spreading. We developed an infectious model of molecular mimicry by
      inserting a sequence encompassing the immunodominant myelin epitope, proteolipid
      protein (PLP) 139-151, into the coding region of a nonpathogenic TMEV variant.
      PLP139-TMEV-infected mice developed a rapid onset paralytic inflammatory,
      demyelinating disease paralleled by the activation of PLP139-151-specific CD4(+)
      Th1 responses within 10-14 days postinfection. The current studies demonstrate
      that the early onset demyelinating disease induced by PLP139-TMEV is the direct
      result of autoreactive PLP139-151-specific CD4(+) T cell responses. PLP139-151
      specific CD4(+) T cells from PLP139-TMEV-infected mice transferred demyelinating
      disease to naive recipients and PLP139-151-specific tolerance before infection
      prevented clinical disease. Finally, infection with the mimic virus at sites
      peripheral to the CNS induced early demyelinating disease, suggesting that the
      PLP139-151-specific CD4(+) T cells could be activated in the periphery and
      traffic to the CNS. Collectively, infection with PLP139-151 mimic encoding TMEV
      serves as an excellent model for molecular mimicry by inducing pathologic myelin
      specific CD4(+) T cells via a natural virus infection.

PMID- 12193747
TI  - Membrane Fas ligand activates innate immunity and terminates ocular immune
      privilege.
AB  - It has been proposed that the constitutive expression of Fas ligand (FasL) in the
      eye maintains immune privilege, in part through inducing apoptosis of
      infiltrating Fas(+) T cells. However, the role of FasL in immune privilege
      remains controversial due to studies that indicate FasL is both pro- and anti
      inflammatory. To elucidate the mechanism(s) by which FasL regulates immune
      privilege, we used an ocular tumor model and examined the individual roles of the
      membrane-bound and soluble form of FasL in regulating ocular inflammation.
      Following injection into the privileged eye, tumors expressing only soluble FasL
      failed to trigger inflammation and grew progressively. By contrast, tumors
      expressing only membrane FasL 1) initiated vigorous neutrophil-mediated
      inflammation, 2) terminated immune privilege, and 3) were completely rejected.
      Moreover, the rejection coincided with activation of both innate and adaptive
      immunity. Interestingly, a higher threshold level of membrane FasL on tumors is
      required to initiate inflammation within the immune privileged eye, as compared
      with nonprivileged sites. The higher threshold is due to the suppressive
      microenvironment found within aqueous humor that blocks membrane FasL activation
      of neutrophils. However, aqueous humor is unable to completely block the
      proinflammatory effects of tumor cells that express high levels of membrane FasL.
      In conclusion, our data indicate that the function of FasL on intraocular tumors
      is determined by the microenvironment in conjunction with the form and level of
      FasL expressed.

PMID- 12193748
TI  - IL-2 receptor blockade inhibits late, but not early, IFN-gamma and CD40 ligand
      expression in human T cells: disruption of both IL-12-dependent and -independent
      pathways of IFN-gamma production.
AB  - mAbs directed against the alpha-chain (Tac/CD25) of the IL-2R are an emerging
      therapy in both transplantation and autoimmune disease. However, the mechanisms
      underlying their therapeutic efficacy have not been fully elucidated. Therefore,
      we examined the effect of IL-2R blockade on Th1 and Th2 cytokine production from
      human PBMC. Addition of a humanized anti-Tac Ab (HAT) to activated PBMC cultures
      inhibited IFN-gamma production from CD4 and CD8 T cells by 80-90%. HAT partially
      inhibited production of TNF-alpha and completely inhibited production of IL-4, IL
      5, and IL-10. Furthermore, IL-12, a central regulatory cytokine that induces IFN
      gamma, was undetectable in treated cultures. As T cell-dependent induction of IL
      12 is regulated via CD40/CD40 ligand (CD40L) interactions, we examined the effect
      of HAT on CD40L expression. We found CD40L expression to be biphasic with an
      early (6 h) peak that is CD28/IL-2-independent, but a later peak (48 h) being
      CD28/IL-2-dependent and inhibited by HAT. Similarly, IFN-gamma production at 6 h
      was CD28/IL-2-independent but CD28/IL-2-dependent and inhibited by HAT at 48 h.
      Nonetheless, addition of rCD40L or exogenous IL-12 to HAT-treated cultures could
      not restore IFN-gamma production. The IFN-gamma deficit in such cultures appears
      to be due to a direct inhibition by HAT of IL-12-independent IFN-gamma production
      from T cells rather than altered expression of either the IL-12Rbeta1 or IL
      12Rbeta2 chains. These data demonstrate that IL-2 plays a critical role in the
      regulation of Th1 and Th2 responses and impacts both IL-12-dependent and 
      independent IFN-gamma production.

PMID- 12193749
TI  - Mycophenolic acid inhibits IL-2-dependent T cell proliferation, but not IL-2
      dependent survival and sensitization to apoptosis.
AB  - Mycophenolic acid (MPA), the active metabolite of the immunosuppressive drug
      mycophenolate mofetil, is a selective inhibitor of inosine 5'-monophosphate
      dehydrogenase type II, a de novo purine nucleotide synthesis enzyme expressed in
      T and B lymphocytes and up-regulated upon cell activation. In this study, we
      report that the blockade of guanosine nucleotide synthesis by MPA inhibits
      mitogen-induced proliferation of PBL, an effect fully reversed by addition of
      guanosine and shared with mizoribine, another inhibitor of inosine 5'
      monophosphate dehydrogenase. Because MPA does not inhibit early TCR-mediated
      activation events, such as CD25 expression and IL-2 synthesis, we investigated
      how it interferes with cytokine-dependent proliferation and survival. In
      activated lymphoblasts that are dependent on IL-2 or IL-15 for their
      proliferation, MPA does not impair signaling events such as of the extracellular
      signal-regulated kinase 2 and Stat5 phosphorylation, but inhibits down-regulation
      of the cyclin-dependent kinase inhibitor p27(Kip1). Therefore, in activated
      lymphoblasts, MPA specifically interferes with cytokine-dependent signals that
      control cell cycle and blocks activated T cells in the mid-G(1) phase of the cell
      cycle. Although it blocks IL-2-mediated proliferation, MPA does not inhibit cell
      survival and Bcl-x(L) up-regulation by IL-2 or other cytokines whose receptors
      share the common gamma-chain (CD132). Finally, MPA does not interfere with IL-2
      dependent acquisition of susceptibility to CD95-mediated apoptosis and
      degradation of cellular FLIP. Therefore, MPA has unique functional properties not
      shared by other immunosuppressive drugs interfering with IL-2R signaling events
      such as rapamycin and CD25 mAbs.

PMID- 12193750
TI  - Prevalence of regulatory T cells is increased in peripheral blood and tumor
      microenvironment of patients with pancreas or breast adenocarcinoma.
AB  - Regulatory T cells (T(reg)) that prevent autoimmune diseases by suppression of
      self-reactive T cells may also suppress the immune response against cancer. In
      mice, depletion of T(reg) by Ab therapy leads to more efficient tumor rejection.
      T(reg)-mediated suppression of antitumor immune responses may partly explain the
      poor clinical response to vaccine-based immunotherapy for human cancer. In this
      study, we measured the prevalence of T(reg) that coexpress CD4 and CD25 in the
      PBLs, tumor-infiltrating lymphocytes, and regional lymph node lymphocytes from 65
      patients with either pancreas or breast cancer. In breast cancer patients (n =
      35), pancreas cancer patients (n = 30), and normal donors (n = 35), the
      prevalence of T(reg) were 16.6% (SE 1.22), 13.2% (SE 1.13), and 8.6% (SE 0.71) of
      the total CD4(+) cells, respectively. The prevalence of T(reg) were significantly
      higher in breast cancer patients (p < 0.01) and pancreas cancer patients (p <
      0.01) when compared with normal donors. In tumor-infiltrating lymphocytes and
      lymph node lymphocytes, the T(reg) prevalence were 20.2% (SE 3.93) and 20.1% (SE
      4.3), respectively. T(reg) constitutively coexpressed CTLA-4 and CD45RO markers,
      and secreted TGF-beta and IL-10 but did not secrete IFN-gamma. When cocultured
      with activated CD8(+) cells or CD4(+)25(-) cells, T(reg) potently suppressed
      their proliferation and secretion of IFN-gamma. We conclude that the prevalence
      of T(reg) is increased in the peripheral blood as well as in the tumor
      microenvironment of patients with invasive breast or pancreas cancers. These
      T(reg) may mitigate the immune response against cancer, and may partly explain
      the poor immune response against tumor Ags.

PMID- 12193751
TI  - New insights into the functionality of a virion-anchored host cell membrane
      protein: CD28 versus HIV type 1.
AB  - It is now well established that the HIV type 1 (HIV-1) incorporates a vast array
      of host-encoded molecules in its envelope during the budding process.
      Interestingly, it was demonstrated that the attachment process is accentuated by
      supplementary interactions between virion-anchored host molecules and their
      cognate ligands. Such an enhancement of the viral attachment process was found to
      result in an increase of infectivity for both T and macrophage-tropic strains of
      HIV-1. Given that previous work indicates that HIV-1 is budding at the site of
      cell-to-cell contact, a location rich in the costimulatory CD28 glycoprotein, we
      investigated whether CD28 could be efficiently acquired by HIV-1. We have been
      able to generate progeny viruses bearing or not bearing on their surfaces host
      derived CD28 using our previously described transient transfection and expression
      system. The physical presence of CD28 was found to markedly increase virus
      infectivity in a CD28/B7-dependent manner following infection of two human
      lymphoid cell lines expressing high levels of surface B7-1/B7-2, two natural
      ligands of CD28. The physiological significance of CD28 incorporation was
      provided by the observation that an anti-CD28 Ab decreased replication in primary
      human mononuclear cells of clinical isolates of HIV-1 propagated in such cells. A
      virus precipitation assay revealed that M-, T-, and dual-tropic clinical strains
      of HIV-1 produced in primary human mononuclear cells do indeed incorporate CD28.
      These results show for the first time that HIV-1 can incorporate CD28 and the
      acquisition of this specific host surface glycoprotein modulates the virus life
      cycle.

PMID- 12193752
TI  - A panel of candidate tumor antigens in colorectal cancer revealed by the
      serological selection of a phage displayed cDNA expression library.
AB  - In the last few years it has been shown that the humoral immune response in
      cancer patients is a rich source of putative cancer vaccine candidates. To fully
      explore the complex information present within the Ab repertoire of cancer
      patients, we have applied a method, serological Ag selection, to molecularly
      define tumor Ags recognized by the humoral immune response in colorectal cancer
      (CRC). First, we built a cDNA display library by cloning a cDNA library from CRC
      cell line HT-29 for expression as a fusion protein with a filamentous phage minor
      coat protein, pVI. This cDNA display library was then enriched on pooled sera
      from CRC patients who had undergone active specific immunization with autologous
      tumor. We identified a panel of 19 clones reactive with the serum pool. Seventeen
      of 19 (89%) clones showed reactivity with one or more of the eight Ag-reactive
      sera, conversely six of eight (75%) sera were reactive with at least one of the
      19 clones. Sequencing revealed that these 19 clones represented 13 different Ags.
      A detailed serological analysis of the 13 different Ags showed preferential
      reactivity to sera of cancer patients for six different Ags. Four of these Ags
      displayed increased serum reactivity after the active specific immunization
      procedure. Furthermore, one of the six Ags, a novel Ag homologous to HSPC218,
      showed restricted expression in normal testis, suggesting that it belongs to the
      cancer-testis Ag family. Some of the Ags we have identified may be candidates for
      tumor vaccination, for sero-diagnosis of cancer, as prognostic markers, or as
      probes for monitoring tumor cell-based vaccination trials.

PMID- 12193753
TI  - Activation of APCs through CD40 or Toll-like receptor 9 overcomes tolerance and
      precipitates autoimmune disease.
AB  - Some autoreactive T cells normally escape thymic selection and persist in the
      periphery. This is true of myelin-reactive CD4(+) T cells, the effectors of
      experimental autoimmune encephalomyelitis (EAE) in laboratory animals and the
      presumed mediators of multiple sclerosis in humans. Nonetheless, most individuals
      do not succumb to autoimmune disease. There is growing evidence that while
      peripheral APCs stimulate immune responses against foreign Ags in the setting of
      tissue destruction and "danger," they actually maintain tolerance against self
      Ags under steady state conditions. We hypothesized that tolerance against
      candidate autoantigens could be reversed by activation of APCs via CD40 or Toll
      like receptor 9 signaling. Adult SJL mice injected i.p. with a peptide fragment
      of proteolipid protein (a candidate autoantigen in multiple sclerosis) emulsified
      in IFA fail to mount lymphoproliferative or cytokine responses and are protected
      from EAE upon subsequent challenge with the Ag combined with adjuvants. Here we
      report that tolerized proteolipid protein-specific lymph node cells regain the
      ability to divide, differentiate along a Th1 lineage, and transfer EAE when
      reactivated in the presence of agonistic Abs against CD40 or CpG
      oligonucleotides. The effects of both anti-CD40 and CpG oligonucleotides are
      dependent upon induction of IL-12. Our findings suggest two mechanisms to explain
      the well-documented association between infectious illnesses and flare-ups of
      multiple sclerosis. Microbial pathogens could 1) release molecules that bind Toll
      like receptors, and/or 2) stimulate microbe-specific T cells to express CD40
      ligand, thereby licensing APCs that bear both microbial and autoantigens to break
      tolerance.

PMID- 12193755
TI  - Not wicked, perhaps, but tacky.

PMID- 12193754
TI  - Generation of CD3+CD8low thymocytes in the HIV type 1-infected thymus.
AB  - Infection with the HIV type 1 (HIV-1) can result both in depletion of CD4(+) T
      cells and in the generation of dysfunctional CD8(+) T cells. In HIV-1-infected
      children, repopulation of the peripheral T cell pool is mediated by the thymus,
      which is itself susceptible to HIV-1 infection. Previous work has shown that MHC
      class I (MHC I) molecules are strongly up-regulated as result of IFN-alpha
      secretion in the HIV-1-infected thymus. We demonstrate in this study that
      increased MHC I up-regulation on thymic epithelial cells and double-positive CD3(
      /int)CD4(+)CD8(+) thymocytes correlates with the generation of mature single
      positive CD4(-)CD8(+) thymocytes that have low expression of CD8. Treatment of
      HIV-1-infected thymus with highly active antiretroviral therapy normalizes MHC I
      expression and surface CD8 expression on such CD4(-)CD8(+) thymocytes. In
      pediatric patients with possible HIV-1 infection of the thymus, a low CD3
      percentage in the peripheral circulation is also associated with a CD8(low)
      phenotype on circulating CD3(+)CD8(+) T cells. Furthermore, CD8(low) peripheral T
      cells from these HIV-1(+) pediatric patients are less responsive to stimulation
      by Ags from CMV. These data indicate that IFN-alpha-mediated MHC I up-regulation
      on thymic epithelial cells may lead to high avidity interactions with developing
      double-positive thymocytes and drive the selection of dysfunctional
      CD3(+)CD8(low) T cells. We suggest that this HIV-1-initiated selection process
      may contribute to the generation of dysfunctional CD8(+) T cells in HIV-1
      infected patients.

PMID- 12193756
TI  - Pharmacogenetics. Gene mutation may boost risk of heart arrhythmias.

PMID- 12193758
TI  - Mathematics. Medals honor work on linkages and proof.

PMID- 12193757
TI  - Contour mission. Comet craft in pieces, astronomers fear.

PMID- 12193760
TI  - Central Europe floods. Labs spared as climate change gets top billing.

PMID- 12193759
TI  - Evolutionary biology. Cool cats lose out in the mane event.

PMID- 12193761
TI  - Animal biotechnology. Environmental impact seen as biggest risk.

PMID- 12193763
TI  - Scientific exchanges. U.S. visa crackdown disrupts meetings.

PMID- 12193762
TI  - Electronic publishing. DOE cites competition in killing PubSCIENCE.

PMID- 12193764
TI  - New therapies. New Alzheimer's treatments that may ease the mind.

PMID- 12193765
TI  - NSAIDS for prevention? Protecting the brain while killing pain?

PMID- 12193766
TI  - Profile: Barbara Hatch Rosenberg. Unconventional detective bears down on a
      killer.

PMID- 12193767
TI  - Climate forecasting. Drought exposes cracks in India's monsoon model.

PMID- 12193768
TI  - Plant genetics. Surviving the long nights: how plants keep their cool.

PMID- 12193769
TI  - Statistical physics. A fresh take on disorder, or disorderly science?

PMID- 12193771
TI  - Genomics. Vertebrate genomes compared.

PMID- 12193770
TI  - Genetics. DNA patenting and licensing.

PMID- 12193772
TI  - Materials science. Dynamics in ceramics.

PMID- 12193773
TI  - Climate. An exceptionally long interglacial ahead?

PMID- 12193774
TI  - Thermodynamics. Water and ice.

PMID- 12193775
TI  - Neuroscience and evolution. Snake sodium channels resist TTX arrest.

PMID- 12193776
TI  - Apoptosis. A cinderella caspase takes center stage.

PMID- 12193777
TI  - Ecological effects of climate fluctuations.
AB  - Climate influences a variety of ecological processes. These effects operate
      through local weather parameters such as temperature, wind, rain, snow, and ocean
      currents, as well as interactions among these. In the temperate zone, local
      variations in weather are often coupled over large geographic areas through the
      transient behavior of atmospheric planetary-scale waves. These variations drive
      temporally and spatially averaged exchanges of heat, momentum, and water vapor
      that ultimately determine growth, recruitment, and migration patterns. Recently,
      there have been several studies of the impact of large-scale climatic forcing on
      ecological systems. We review how two of the best-known climate phenomena-the
      North Atlantic Oscillation and the El Nino-Southern Oscillation-affect ecological
      patterns and processes in both marine and terrestrial systems.

PMID- 12193778
TI  - Failure of bone marrow cells to transdifferentiate into neural cells in vivo.

PMID- 12193779
TI  - Structural studies of several distinct metastable forms of amorphous ice.
AB  - Structural changes during annealing of high-density amorphous ice were studied
      with both neutron and x-ray diffraction. The first diffraction peak was followed
      from the high- to the low-density amorphous form. Changes were observed to occur
      through a series of intermediate forms that appear to be metastable at each
      anneal temperature. Five distinct amorphous forms were studied with neutron
      scattering, and many more forms may be possible. Radial distribution functions
      indicate that the structure evolves systematically between 4 and 8 angstroms. The
      phase transformations in low-temperature liquid water may be much more complex
      than currently understood.

PMID- 12193780
TI  - The vibration-rotation emission spectrum of free BeH2.
AB  - The gaseous BeH2 molecule has been synthesized by means of an electrical
      discharge inside a high-temperature furnace and identified with infrared emission
      spectroscopy. The antisymmetric stretching mode nu3 has been detected near 2179
      reciprocal centimeters. The BeH2 molecule has a linear, symmetric structure with
      an r0 BeH bond length of 1.333761(2) angstroms.

PMID- 12193781
TI  - An archean impact layer from the Pilbara and Kaapvaal cratons.
AB  - The Barberton greenstone belt of South Africa and the eastern Pilbara block of
      Western Australia provide information about Earth's surface environments between
      3.2 and 3.5 billion years ago, including evidence for four large bolide impacts
      that likely created large craters, deformed the target rocks, and altered the
      environment. We have obtained identical single-zircon uranium-lead ages of 3470
      +/- 2 million years ago for the oldest impact events from each craton. These
      deposits represent a single global fallout layer that is associated with
      sedimentation by an impact-generated tsunami and in Western Australia is
      represented by a major erosional unconformity.

PMID- 12193782
TI  - C-O bond formation by polyketide synthases.
AB  - Polyketide synthases (PKSs) assemble the polyketide carbon backbone by sequential
      decarboxylative condensation of acyl coenzyme A (CoA) precursors, and the C-C
      bond-forming step in this process is catalyzed by the beta-ketoacyl synthase (KS)
      domain or subunit. Genetic and biochemical characterization of the nonactin
      biosynthesis gene cluster from Streptomyces griseus revealed two KSs, NonJ and
      NonK, that are highly homologous to known KSs but catalyze sequential
      condensation of the acyl CoA substrates by forming C-O rather than C-C bonds.
      This chemistry can be used in PKS engineering to increase the scope and diversity
      of polyketide biosynthesis.

PMID- 12193783
TI  - Variant of SCN5A sodium channel implicated in risk of cardiac arrhythmia.
AB  - Every year, approximately 450,000 individuals in the United States die suddenly
      of cardiac arrhythmia. We identified a variant of the cardiac sodium channel gene
      SCN5A that is associated with arrhythmia in African Americans (P = 0.000028) and
      linked with arrhythmia risk in an African-American family (P = 0.005). In
      transfected cells, the variant allele (Y1102) accelerated channel activation,
      increasing the likelihood of abnormal cardiac repolarization and arrhythmia.
      About 13.2% of African Americans carry the Y1102 allele. Because Y1102 has a
      subtle effect on risk, most carriers will never have an arrhythmia. However,
      Y1102 may be a useful molecular marker for the prediction of arrhythmia
      susceptibility in the context of additional acquired risk factors such as the use
      of certain medications.

PMID- 12193784
TI  - Mechanisms of adaptation in a predator-prey arms race: TTX-resistant sodium
      channels.
AB  - Populations of the garter snake Thamnophis sirtalis have evolved geographically
      variable resistance to tetrodotoxin (TTX) in a coevolutionary arms race with
      their toxic prey, newts of the genus Taricha. Here, we identify a physiological
      mechanism, the expression of TTX-resistant sodium channels in skeletal muscle,
      responsible for adaptive diversification in whole-animal resistance. Both
      individual and population differences in the ability of skeletal muscle fibers to
      function in the presence of TTX correlate closely with whole-animal measures of
      TTX resistance. Demonstration of individual variation in an essential
      physiological function responsible for the adaptive differences among populations
      is a step toward linking the selective consequences of coevolutionary
      interactions to geographic and phylogenetic patterns of diversity.

PMID- 12193785
TI  - Sexual selection, temperature, and the lion's mane.
AB  - The mane of the African lion (Panthera leo) is a highly variable trait that
      reflects male condition and ambient temperature. We examined the consequences of
      this variation in a long-term study of lions in the Serengeti National Park,
      Tanzania. Mane darkness indicates nutrition and testosterone and influences both
      female choice and male-male competition. Mane length signals fighting success and
      only appears to influence male-male assessment. Dark-maned males enjoy longer
      reproductive life-spans and higher offspring survival, but they suffer higher
      surface temperatures, abnormal sperm, and lower food intake during hot months of
      the year. Maned males are hotter than females, and males have lighter and/or
      shorter manes in hotter seasons, years, and habitats. This phenotypic plasticity
      suggests that the mane will respond to forecasted increases in ambient
      temperature.

PMID- 12193786
TI  - Meiotic arrest in the mouse follicle maintained by a Gs protein in the oocyte.
AB  - The mammalian ovarian follicle consists of a multilayered complex of somatic
      cells that surround the oocyte. A signal from the follicle cells keeps the oocyte
      cell cycle arrested at prophase of meiosis I until luteinizing hormone from the
      pituitary acts on the follicle cells to release the arrest, causing meiosis to
      continue. Here we show that meiotic arrest can be released in mice by
      microinjecting the oocyte within the follicle with an antibody that inhibits the
      stimulatory heterotrimeric GTP-binding protein Gs. This indicates that Gs
      activity in the oocyte is required to maintain meiotic arrest within the ovarian
      follicle and suggests that the follicle may keep the cell cycle arrested by
      activating Gs.

PMID- 12193787
TI  - Distinct modes of signal recognition particle interaction with the ribosome.
AB  - Signal recognition particle (SRP), together with its receptor (SR), mediates the
      targeting of ribosome-nascent chain complexes to the endoplasmic reticulum. Using
      protein cross-linking, we detected distinct modes in the binding of SRP to the
      ribosome. During signal peptide recognition, SRP54 is positioned at the exit site
      close to ribosomal proteins L23a and L35. When SRP54 contacts SR, SRP54 is
      rearranged such that it is no longer close to L23a. This repositioning may allow
      the translocon to dock with the ribosome, leading to insertion of the signal
      peptide into the translocation channel.

PMID- 12193788
TI  - Fusion pore dynamics and insulin granule exocytosis in the pancreatic islet.
AB  - Insulin secretion from intact mouse pancreatic islets was investigated with two
      photon excitation imaging. Insulin granule exocytosis occurred mainly toward the
      interstitial space, away from blood vessels. The fusion pore was unusually stable
      with a lifetime of 1.8 seconds. Opening of the 1.4-nanometer-diameter pore was
      preceded by unrestricted lateral diffusion of lipids along the inner wall of the
      pore, supporting the idea that this structure is composed of membrane lipids.
      When the pore dilated to 12 nanometers, the granules rapidly flattened and
      discharged their contents. Thus, our methodology reveals fusion pore dynamics in
      intact tissues at nanometer resolution.

PMID- 12193789
TI  - Requirement for caspase-2 in stress-induced apoptosis before mitochondrial
      permeabilization.
AB  - A current view is that cytotoxic stress, such as DNA damage, induces apoptosis by
      regulating the permeability of mitochondria. Mitochondria sequester several
      proteins that, if released, kill by activating caspases, the proteases that
      disassemble the cell. Cytokines activate caspases in a different way, by
      assembling receptor complexes that activate caspases directly; in this case, the
      subsequent mitochondrial permeabilization accelerates cell disassembly by
      amplifying caspase activity. We found that cytotoxic stress causes activation of
      caspase-2, and that this caspase is required for the permeabilization of
      mitochondria. Therefore, we argue that cytokine-induced and stress-induced
      apoptosis act through conceptually similar pathways in which mitochondria are
      amplifiers of caspase activity rather than initiators of caspase activation.

PMID- 12193790
TI  - hamlet, a binary genetic switch between single- and multiple- dendrite neuron
      morphology.
AB  - The dendritic morphology of neurons determines the number and type of inputs they
      receive. In the Drosophila peripheral nervous system (PNS), the external sensory
      (ES) neurons have a single nonbranched dendrite, whereas the lineally related
      multidendritic (MD) neurons have extensively branched dendritic arbors. We report
      that hamlet is a binary genetic switch between these contrasting morphological
      types. In hamlet mutants, ES neurons are converted to an MD fate, whereas ectopic
      hamlet expression in MD precursors results in transformation of MD neurons into
      ES neurons. Moreover, hamlet expression induced in MD neurons undergoing dendrite
      outgrowth drastically reduces arbor branching.

PMID- 12193791
TI  - Department of Health Donor Information Consultation: providing information about
      gamete or embryo donors.

PMID- 12193792
TI  - Fertility preservation in cancer patients.
AB  - This symposium was an international gathering of clinicians and scientists
      working in the field of preservation of fertility for male and female cancer
      patients and was organized by Professor Ettore Cittadini. Two days of invited
      lectures covered the spectrum of options for cryopreservation of fertility, from
      sperm, testicular tissue and germ cells, to eggs and ovarian tissue. The UK was
      represented by invited talks from Daniel Brison (sperm cryopreservation), John
      Radford (ovarian tissue cryopreservation), Kate Hardy (in vitro culture of
      follicles) and David Baird (ovarian tissue cryopreservation and regrafting in
      sheep).

PMID- 12193793
TI  - Importance of mitochondrial and nuclear sperm DNA in sperm quality assessment and
      assisted reproduction outcome.
AB  - Intracytoplasmic sperm injection (ICSI) has made irrelevant the conventional
      criteria of concentration, motility and morphology for assessment of sperm
      quality and so we urgently need new assays by which to gauge sperm 'health'. ICSI
      may be facilitating the transfer of genetic disorders to future generations by
      bypassing all the natural hurdles for sperm selection without imposing more
      pertinent criteria of selection. Sperm DNA quality is vital to the future
      offspring irrespective of whether the child is conceived naturally, by in vitro
      fertilization (IVF) or by ICSI. The DNA integrity of sperm can be determined
      quickly and accurately using a range of techniques that also have strong
      prognostic power in predicting successful IVF and ICSI outcomes with ejaculated
      sperm. Moreover, there is a close correlation between testicular nuclear DNA
      integrity and pregnancy rates in ICSI. Mitochondrial DNA can be measured using
      long PCR in ejaculated and testicular sperm and is also useful for predicting
      success in assisted conception. This review discusses how the integrity of both
      nuclear and mitochondrial affect the choice of sperm for assisted conception.

PMID- 12193794
TI  - Fate of sperm components during assisted reproduction: implications for
      infertility.
AB  - Studies in non-human primates highlight their suitability as preclinical models
      for investigating assisted reproduction techniques. The cytoskeletal events of
      fertilization in non-human primates are similar to those in humans in that they
      require a paternally derived centrosome. The centrosome, introduced by the sperm
      at fertilization, organizes a microtubule array that is responsible for bringing
      the parental genomes together at first mitosis. Incomplete functioning of the
      sperm centrosome during fertilization has been identified as a novel form of
      infertility that would not necessarily benefit from intracytoplasmic sperm
      injection (ICSI). The global use of ICSI to overcome male infertility has been
      very successful, although concerns remain regarding the long-term effects on
      children born after ICSI. The cytoskeletal events that occur during ICSI are
      quite different from the events of in vitro fertilization: a sperm selected for
      ICSI does not undergo typical oocyte interactions, and abnormal remodelling of
      the male pronucleus may result. The implications of these findings are discussed
      in relation to the safety of the ICSI technique.

PMID- 12193795
TI  - Fertility after laparoscopic surgery for endometriomas.
AB  - There are a number of published studies documenting pregnancy rates after
      endoscopic surgery in patients with endometriomas. These reports present similar
      pregnancy rates regardless of the surgical technique used to treat the cyst. This
      finding indicates that it does not matter whether the endometrioma is excised or
      ablated. However, debate about the nature of the cleavage plane of the cyst has
      led some surgeons to suggest that excision may damage the follicular reserve of
      the ovary. Furthermore, pregnancy rates after surgery cannot be compared in the
      same way as pregnancy rates after in vitro fertilization and embryo transfer
      because of lack of standardization. A review of the published studies relating to
      the laparoscopic management of endometriomas was performed to examine this issue
      further. Each paper was analysed using pre-set criteria to identify the
      methodology used and how the results were presented. Wide variation was found in
      the criteria used to select patients and in the way the results were reported. In
      view of these findings, there is an urgent need for surgical studies with
      consistent definitions of infertility and end-points, or a national system of
      audit.

PMID- 12193796
TI  - Unexpected application of counselling skills by a fertility research nurse.
AB  - Men attending the Andrology Laboratory for the first time were asked to complete
      questionnaires regarding their employment, lifestyle, diet and infancy for the
      Chemicals and Pregnancy Study UK (CHAPS-UK) research study. CHAPS-UK is a multi
      centre study investigating reasons for male infertility. During one interview, a
      patient expressed concerns about his sexual relationship with his wife.
      Initially, he described his concerns about infertility but as the nurse used her
      counselling skills, the patient was able to voice his psychosexual difficulties.
      This was the first time in 5 years of marriage the patient talked about his
      situation to another person. The research nurse was able to combine good
      communication and counselling skills to facilitate the patient's need to face his
      problem, which enabled him to make a constructive decision about his need for
      further help. This case highlights the difficult situation in which fertility
      nurses can find themselves and reinforces the need for nurses involved in the
      care of infertile couples to have training in counselling skills and the ability
      to make appropriate referral to an infertility counsellor when required.

PMID- 12193797
TI  - Health needs of adolescents in secondary gynaecological care: results of a
      questionnaire survey and a review of current issues.
AB  - The objective of this study was to undertake a survey of all obstetrics and
      gynaecology units in the United Kingdom to identify current views and facilities
      for the management of adolescents with gynaecological problems. A postal
      questionnaire was sent to all 248 departments of obstetrics and gynaecology in
      the UK. The survey was carried out by the Royal College of Obstetricians and
      Gynaecologists on behalf of the Royal College of Paediatrics and Child Health
      Intercollegiate Working Group on Adolescent Health. In total, 137 replies were
      received, giving a response rate of 55%. Only eight centres were able to quote an
      exact figure for the number of adolescent attendees and this ranged from 0.0035%
      to 4.8% of new gynaecological referrals. The cut-off age for paediatric patients
      ranged from 12 to 18 years. In response to the question regarding the definition
      of 'adolescence', most units that responded stated the range 12-16 years (81
      units) and a further 30 units stated 12-18 years. Despite these large variations
      and also the lack of certainty of both the age range of adolescents and local
      criteria, 64 units considered that adolescents in their area had special needs,
      mainly for family planning issues, teenage pregnancy and drug or alcohol abuse.
      Sixty-three units (46%) provided family planning clinics for adolescents, 24
      (17.5%) had a teenage pregnancy clinic, 22 (16.1%) had an adolescent sexual
      health clinic and 11 (8%) had a clinic for intersex conditions and developmental
      disorders. In conclusion, there is no consensus on the age range of the
      adolescent population and a lack of data on the numbers of adolescents with
      different obstetric and gynaecological problems. There is a perceived need for
      better data collection and designated facilities for adolescents who have
      gynaecological problems. Currently, there are no national guidelines for the
      management and referral of specialized problems, which should be addressed as a
      matter of urgency.

PMID- 12193798
TI  - A circadian neuropeptide, pigment-dispersing factor-PDF, in the last-summer
      cicada Meimuna opalifera: cDNA cloning and immunocytochemistry.
AB  - Pigment-dispersing factor (PDF), an 18-amino acid neuropeptide, is a principal
      circadian neuromodulator functioning downstream of the insect brain's circadian
      clock, modulating daily rhythms of locomotor activity. Recently, we found that
      PDF precursors of the cricket Gryllus bimaculatus comprise a nuclear localization
      signal (NLS). Moreover, the nuclear localization of PDF immunoreactivity and the
      translocation of GFP-fused PDF precursor into the nucleus have both been
      demonstrated. These suggest a fundamental role for PDF peptide in the circadian
      clock system within the nucleus, in addition to its role in downstream neural
      events. In the present study, we carried out the cDNA cloning of PDF from adult
      brains of the last-summer cicada Meimuna opalifera, and found that an isolated
      clone (545 bp) encodes an ordinary PDF precursor protein. PDF peptide itself
      shows a high sequence identity (78-94%) and similarity (89-100%) to insect PDFs
      and also to the crustacean beta-PDH peptides. The computer-assisted sequence
      analysis of PDF precursor revealed a possible translocation into the nucleus,
      despite the lack of a definite NLS-like sequence. Using immunocytochemistry, the
      optic lobes of M. opalifera revealed PDF-immunoreactive neurons in both the
      medulla and lamina neuropiles. All these PDF cells exhibited prominent
      immunolabeling of both their perikarya and axons, but not their nuclei. Our
      results provide the first structural and immunocytochemical identification of PDF
      neurons in Hemiptera.

PMID- 12193799
TI  - An increase in extracellular Ca(2+) concentration induces pigment aggregation in
      teleostean melanophores.
AB  - An increase in the concentration of Ca(2+) ions in the external medium
      ([Ca(2+)](o)) induced pigment aggregation in melanophores of three species of
      freshwater teleosts examined. Denervated melanophores were refractory to
      elevations of [Ca(2+)](o). The pigment-aggregating action was inhibited by the
      sympathetic blocking agents, phentolamine, prazosin and yohimbine. Bretylium, an
      agent known to block the release of the neurotransmitter, interfered with the
      response effectively. Ca(2+) blockers, such as Mn(2+), verapamil and gallopamil,
      also inhibited the response, possibly by inhibiting Ca(2+) entry into the
      presynaptic elements of melanosome-aggregating fibers. The conclusion is that the
      increase in [Ca(2+)](o) may induce membrane depolarization of presynaptic nervous
      elements around the melanophores, which open the voltage-dependent Ca(2+)
      channels there. The liberation of adrenergic neurotransmitter follows, which
      induces the aggregation of pigment in melanophores.

PMID- 12193802
TI  - The drumming of Isoperla pallida Aubert and Guadalgenus franzi (Aubert)
      (Plecoptera, Perlodidae), and review and evolutionary considerations of Southern
      Iberian Peninsula Perlodidae.
AB  - The drumming calls of two perlodid species from Southern Spain (Sierra Morena,
      Jaen) are analyzed and described. Nineteen calls from one male of Guadalgenus
      franzi were recorded, showing a simple call pattern composed of two beats with an
      average duration between them of 184.32 msec (range: 165-227). This is the
      simplest call pattern yet discovered in the Plecoptera. The female of this
      species also presented a simple call consisting of only one beat. The male of
      Isoperla pallida showed an ancestral call pattern, more simple than the other
      Iberian Isoperla species (I. grammatica, I. nevada or I. curtata, all of them
      with multiphasic drumming calls or I. bipartita with a notably different model
      consisting of rubbing). Calls from six different males (the female did not drum)
      consisted of an average of 65.94 beats (range: 25-83) with a duration average of
      1462.69 msec (range: 548-1835), regularly repeated with intervals with a duration
      average of 22.27 msec (range: 17-30). With this study, the vibrational calls of
      all the Perlodid species from the Southern Iberian Peninsula, except Perlodes
      microcephalus and Besdolus bicolor, are known. Moreover, it presents the first
      record and description of the call of the monospecific genus Guadalgenus. An
      evolutionary approach to the vibrational communication diversification in the
      perlodids of the Southern Iberian Peninsula is presented, showing a complexity
      graduation from the more simple drumming calls (shown by Hemimelaena flaviventris
      and G. franzi) to the rubbing call of I. bipartita and intermediate drumming
      calls of other Isoperla species, consistent with the drumming evolution paradigm
      of Stewart (2001).

PMID- 12193801
TI  - The force driving mating behavior in the house musk shrew (Suncus murinus).
AB  - The mating behavior of the domesticated house musk shrew was observed in detail
      under laboratory conditions. The observations revealed that the house musk shrew
      has a series of behaviors before copulation. Tactile, auditory and chemical
      senses appear to function as flags for the recognition of conspecifics and to
      promote the development of an interaction between the sexes. The tactile senses
      and the use of the snout were particularly important in the mating sequence, and
      mutual contact appeared to give rise to driving the sequence to completion. The
      two sexes contacted each other 'politely', came to mounting by continuous
      following, and the male finished with a series of post-ejaculatory offensive
      behaviors and scent markings. The variation in the contact reduced once the
      female commenced tail-wagging. The ratio of the time spent in front-and-behind
      contact to that spent in multi-lateral contact increased when both sexes
      commenced following formation. This ratio was maintained until the male's post
      ejaculatory offensive behavior finished. The series of mating behavior was
      completed by the continuous touching of both sexes and by changes in the manner
      of contact.

PMID- 12193800
TI  - A temperature-dependent timing mechanism is involved in the circadian system that
      drives locomotor rhythms in the fruit fly Drosophila melanogaster.
AB  - The circadian clock of Drosophila melanogaster is thought to include rhythmic
      expression of period gene. Recent studies suggested, however, that a per-less
      oscillation is also involved in the regulation of circadian locomotor rhythms. In
      the present study, we examined the existence and the property of the possible per
      less oscillation using arrhythmic clock mutant flies carrying per (01), tim(01),
      dClk(Jrk) or cyc(01), which lack rhythmic per expression. When temperature cycles
      consisting of 25 degrees C and 30 degrees C with various periods (T=8-32 hr) were
      given, wild-type (Canton-S) flies showed locomotor rhythms entrained to
      temperature cycles over a wide range of period (T=8-32 hr) in constant light (LL)
      while only to T=24 hr in constant darkness (DD). The mutant flies showed rhythms
      synchronizing with the given cycle both under LL and DD. In per(01) and tim(01)
      flies, the phase of a major peak slightly changed dependent on Ts in DD, while it
      did not in dClk(Jrk) and cyc(01) flies. When they were transferred from a
      constant temperature to a temperature cycle under DD, several cycles were
      necessary to establish a clear temperature entrainment in per(01) and tim (01)
      flies. These results suggest that per(01) and tim(01) flies have a temperature
      entrainable weak oscillatory mechanism and that the per-less oscillatory
      mechanism may require dClk and cyc. In addition, per (01) and tim(01) flies
      changed from thermoactive in DD to cryoactive in LL, while dClk(Jrk) and cyc(01)
      flies did not. It is thus suggested that dClk and cyc are also involved in
      determining the light-associated temperature preference in per(01) and tim(01)
      flies.

PMID- 12193803
TI  - Developmental capacity and chromosome number in the offspring of artificially
      produced autotetraploids of Rana nigromaculata.
AB  - A large number of autotetraploids of Rana nigromaculata were produced in order to
      assess their developmental capacity and chromosome number in their offspring. An
      original autotetraploid male was first produced by transplanting a nucleus from
      an embryo (triploid) into an unfertilized egg. Next, eggs were inseminated with
      sperm of the autotetraploid male, then cold-treated to obtain first-, second-,
      and third-generation offspring. According to an investigation of the chromosome
      numbers of the tadpoles by the tail-tip squash method, the three generations of
      offspring included many tetraploids (50-80%), as well as some diploids,
      triploids, hexaploids and mosaics at the early tadpole stage. In addition,
      several percent of the second-and third-generation offspring were found to be
      aneuploids. Evidently, a complete set of diploid chromosomes was not precisely
      transferred to all of the next-generation offspring from the sperm of the
      artificially produced autotetraploid males. These observations suggest that there
      were some abnormalities in the course of spermatogenesis in the male
      autotetraploid frogs.

PMID- 12193804
TI  - Neural marker genes differently expressed in subsets of embryonic neural cells of
      the ascidian Halocynthia roretzi.
AB  - Ascidians are lower chordates that possess a possible prototype of the vertebrate
      nervous system. The central and peripheral nervous systems of ascidian larvae are
      composed of only a few hundred cells (Nicol and Meinertzhagen, 1991). To
      investigate how these ascidian nervous systems develop, dissection at the
      molecular level using subset-specific markers is essential. Here we describe four
      new genes zygotically expressed in subsets of the ascidian neural cells. The
      spatial expression domains of these genes overlap in some parts but not in other
      parts of the nervous systems. Our results suggest that there are functionally
      different regions in the nervous systems owing to the gene expression
      differences. Further analyses of these genes will enable us to determine the
      molecular neuro-developmental characteristics of various clusters of neural
      cells.

PMID- 12193805
TI  - Circadian changes in serum concentrations of steroids in Japanese char Salvelinus
      leucomaenis at the stage of final maturation.
AB  - Circadian changes in serum concentrations of testosterone (T), 11
      ketotestosterone (11KT), estradiol-17beta (E2), 17alpha,20beta-dihydroxy-4
      pregnen-3-one (DHP), 17alpha-hydroxyprogesterone (OHP), cortisol (F) and
      progesterone (P) were investigated in the spermiated/ovulated Japanese char
      Salvelinus leucomaenis for over three days using newly developed time-resolved
      fluoroimmunoassays. Testosterone and DHP in both sex and 11KT in male showed
      significantly (P<0.05) higher serum levels just before/after onset of darkness
      (15:00 or 18:00), and the levels during night and daytime were significantly
      (P<0.05) lower than those of the peak levels. Serum F levels in both sex during
      dark phase were significantly (P<0.05) higher than those levels during daytime. A
      surge of serum OHP concentrations in both sexes was observed at the time of
      twilight (03:00). The peak time of serum T, 11KT and DHP levels were
      approximately 6 hours prior to those of serum F and OHP levels. Serum E2 in
      female and P in both sex fluctuated intensely during sampling period, and did not
      show remarkable changes. These results strongly suggest the existence of
      circadian-like diel changes in serum T, DHP, F and OHP levels in both sex and
      11KT in male, and no variations in serum E2 in female and P in both sex in
      spermiated/ovulated Japanese char under the stage of final maturation.
      Furthermore, relationship between circadian rhythms of steroid hormones and
      spawning behaviors are discussed in the present study.

PMID- 12193806
TI  - Egg transport in the coelom of the newt cynops pyrrhogaster. I. The ovulated egg
      is transported to the ostium by the ciliary movement of coelomic epithelial
      cells.
AB  - We investigated the mechanism of egg transport in the newt not only by inserting
      various conditioned eggs into the recipient's body but also by placing them on
      the coelomic epithelia of the opened body cavity in the adult female newt. Most
      of the inserted coelomic eggs were oviposited, while 4 of 14 inserted de-jellied
      uterine eggs and 3 of 10 inserted de-jellied fertilized eggs were oviposited. The
      coelomic eggs placed on the coelomic epithelia were transported toward the ostium
      and entered the ostium. The de-jellied uterine eggs and the de-jellied fertilized
      eggs were transported to the ostium as well. Of all the eggs examined, the
      coelomic egg was transported the fastest. The transport speeds of coelomic eggs
      treated with periodic acid and the speed of boiled coelomic eggs were less than
      those of untreated coelomic eggs. In contrast, the transport speeds of coelomic
      eggs treated with trypsin and the speed of coelomic eggs removed from their
      vitelline envelopes (naked eggs) were faster than those of untreated coelomic
      eggs. Other experiments were carried out in order to ascertain the dependence of
      sexual activity on egg transport. The speed of coelomic egg transport in
      artificially sexually activated females was faster than in sexually inactive
      females, although the ciliary movement could always be observed in both sexually
      active females and sexually inactive females. This suggests that the speed of egg
      transport on the coelomic epithelia is controlled by the sexual activity of the
      female.

PMID- 12193807
TI  - Offshore insular variation in the diet of the Taiwanese bamboo viper Trimeresurus
      stejnegeri (Schmidt).
AB  - Dietary data were ascertained for 229 T. stejnegeri (snout vent length >300mm)
      from 36 localities throughout the main island of Taiwan and the outlying Orchid
      (Lanyu) and Green (Ludau) Islands. Twenty nine percent of the snakes were devoid
      of any prey, and of the snakes containing prey, 43% of the cases were
      unidentifiable. This relatively large proportion of unidentifiable prey items
      (observed in the hindgut) may reflect either rapid digestion of amphibian prey
      and/or rapid venting of feces as an evolutionary adaptation to arboreal life.
      Trimeresurus stejnegeri appears euryphagous, taking primarily amphibians, but
      additionally reptilian, mammalian and insect prey. There was no discrepancy in
      prey composition based on comparisons of where the prey item was recorded in the
      digestive tract. No sexual variation in diet composition was evident, although
      males were more likely to contain prey than females, indicating the utilisation
      of different foraging strategies on similar sympatric prey items. Variation in
      diet composition was observed between mainland Taiwan and offshore islands, which
      is most likely the result of differences in prey availability.

PMID- 12193808
TI  - A preliminary study on relationships among selected Australian members of the
      tribe Spilomelini (Lepidoptera: Crambidae: Pyraustinae).
AB  - A preliminary study was conducted on phylogenetic relationships among some
      selected genera of the Australian Spilomelini, focusing on relationships among
      the Australian Glyphodes group (Glyphodes Guenee, 1854, Dysallacta Lederer, 1863,
      Talanga Moore, 1885 and Agrioglypta Meyrick, 1932) and the 17 genera which are
      morphologically similar to it. Representatives of three genera of the Pyarustini
      were used as outgroups. Cladistic analysis of morphological data from the adult
      moths produced 10 equally MP trees (length = 221, CI=0.294, and RI=0.608). The
      clade formed by the 21 selected genera of the Australian Spilomelini had low
      bootstrap support even though a good apomorphy supported the monophyly of this
      group, namely, a strong, bilobed praecinctorium of abdominal tympanal organs. The
      analysis showed that the Glyphodes group is not monophyletic because the genus
      Chrysothyridia Snellen appears within it in the 10 MP trees. The concept of the
      Glyphodes group should be expanded to include Chrysothyridia and also the
      Synclera Zeller and Didymostoma (Walker) since the Synclera + Didymostoma clade,
      as the hypothesised sister group of the Glyphodes group, is not sufficiently
      supported as a separate monophyletic group. The analysis also showed that genus
      Glyphodes is not a monophyletic group, while Metallarcha Meyrick is a
      monophyletic group.

PMID- 12193809
TI  - Phylogenetic relationships between Vorticella convallaria and other species
      inferred from small subunit rRNA gene sequences.
AB  - Vorticellid ciliates generally dwell in freshwater. In nature, the species have
      up until now been identified by comparison with previous descriptions. It is
      difficult to identify between species of the genus Vorticella, because the
      morphological markers of vorticellid ciliates described in reports are limited
      and variable. Unfortunately, culturing them has only succeeded with certain
      species such as Vorticella convallaria, but many others have been impossible to
      culture. To find out whether the sequence of a small subunit rRNA gene was an
      appropriate marker to identify vorticellid ciliates, the gene was aligned and
      compared. Finding a new convenient method will contribute to research on
      vorticellid ciliates. In strains of V. convallaria, classified morphologically,
      some varieties of the SSrRNA gene sequences were recognized, but there were large
      variations within the same species. According to the phylogenetic tree, these
      strains are closely related. However, the difference was not as big as between
      Vorticella and Carchesium. In addition, Carchesium constructed a distinct clade
      from the genus Vorticella and Epistylis. These results show the possibility that
      the SSrRNA gene is one of the important markers to identify species of
      Vorticella. This study is first to approach and clarify the complicated taxa in
      the genus Vorticella.

PMID- 12193810
TI  - Three new species of the genus Gammarus (Crustacea, Amphipoda, Gammaridae) from
      Yunnan, China.
AB  - Three new species of the genus Gammarus are described from Lijiang, Yunnan
      Province, South China. Gammarus elevatus sp. nov. is characterized by mid-dorsal
      keel on pleonites 1-3 and compressed elevation on urosomites 1-2; G. denticulatus
      sp. nov. by many small spinules and setae on pleonites 1-3; G. stagnarius sp.
      nov. by lack of calceoli on antenna 2 and shorter inner ramus of uropod 3. These
      amphipods are compared with other known Gammarus species from China.

PMID- 12193811
TI  - The behavior and the morphology of sea lilies with shortened stalks: implications
      on the evolution of feather stars.
AB  - Extant crinoids can be divided into two groups, stalked sea lilies and stalkless
      feather stars. Feather stars are considered to have evolved from stalked
      ancestors by losing most of the stalk, but other differences are present between
      the two groups. The unsegmented centrodorsal, long and curved cirri near the
      crown, small calyx, and the ability to swim are all feather star features not
      found in the sea lilies. To figure out which of the above features evolved
      directly correlating with loss of the stalk in feather stars, we cut off the
      stalk from the sea lily Metacrinus rotundus and kept them alive in an aquarium.
      The specimens with shortened stalks were able to stand and crawl with their arms
      without the support of their stalks, but swimming was not observed for any of the
      animals. Morphologically, neither fusion of the remaining segments nor the
      reduction of the size of the calyx were observed, but the cirri became long and
      curved near the crown. Therefore, the extant sea lilies possess a potential to
      adapt to incidents of stalk loss. Specimens autotomizing most of their stalks
      were observed, suggesting that the potential is actually employed in nature. This
      mechanism linking the reduction of the stalk and the changes in the morphology of
      cirri may have played an important role in the evolution of the feather stars, if
      the stalked ancestors of feather stars also possessed this potential.
      Experimental zoological approaches as this study may provide new insights to the
      questions of evolution.

PMID- 12193812
TI  - Thoracoscopy/laparoscopy in the staging of esophageal cancer: Maryland
      experience.
AB  - Precise clinical staging of esophageal cancer before treatment is important.
      Thoracoscopic/laparoscopic (Ts/Ls) staging has been proposed as a promising
      staging method. This study was conducted to evaluate the potential benefits of
      Ts/Ls staging over conventional noninvasive clinical staging in patients with
      esophageal cancer. From 1991 to 1999, 111 patients with esophageal cancer
      underwent Ts/Ls staging by the University of Maryland Medical System.
      Pretreatment staging workup included computed tomography, magnetic resonance
      imaging, and esophageal ultrasonography, followed by Ts/Ls surgical staging.
      Thoracoscopy was successfully performed in 102 patients and was aborted in 4
      patients because of pleural adhesions. Laparoscopy was successfully done in 76
      patients and was aborted in 1 patient because of peritoneal adhesion. Sixty-seven
      patients had both Ts and Ls staging, whereas 35 patients and 9 patients,
      respectively, had only Ts or Ls staging. Thirteen of 19 patients with clinical T4
      disease were downstaged to T3 disease, and 8 patients with clinical T3 disease
      were upstaged to T4 by Ts/Ls staging. No clinical T1-2 disease was found to be
      associated with local invasion (T4) by Ts/Ls. Forty-eight and 19 patients had
      mediastinal and celiac lymph node metastases clinically diagnosed, respectively.
      Nine (18.8%) and 12 (63.2%) of them were proved by Ts and Ls, respectively. An
      additional 5 and 16 patients were found to have unexpected mediastinal and celiac
      lymph node metastases, respectively, by Ts/Ls. Biopsy specimens of pleura, lung,
      or liver were obtained by Ts/Ls procedures in 17 patients because of suspicious
      findings of routine imaging studies or unexpected findings during the staging
      operation. Five patients were found to have distant metastasis, and the presence
      of metastases in others was excluded. The correlation between Ts/Ls staging and
      conventional noninvasive clinical staging in the diagnosis of T4 disease,
      mediastinal lymph node metastasis, celiac lymph node metastasis, and M1 disease
      was 18.8%, 14.5%, 25.5%, and 20.0%, respectively. Ts/Ls provides more accurate
      information for evaluating local invasion, lymph node metastasis, and distant
      metastasis. The poor correlation of staging diagnosis between Ts/Ls and
      conventional noninvasive clinical examinations suggests that the accuracy of
      current noninvasive clinical staging is questionable and needs to be improved.

PMID- 12193813
TI  - Case-control comparison of endoscopic gastroplication with laparoscopic
      fundoplication in the management of gastroesophageal reflux disease: early
      symptomatic outcomes.
AB  - Endoscopic gastroplication is a new technique in the management of
      gastroesophageal reflux disease. No comparisons of this technique with
      laparoscopic fundoplication have been done. Twenty-seven patients with symptoms
      of reflux disease were evaluated with upper endoscopy, esophageal manometry, and
      24-hour esophageal pH monitoring, as well as a symptom severity questionnaire.
      Patients then underwent endoscopic gastroplication with use of the Bard
      Interventional Endoscopic Suturing System. Patients completed the symptom
      severity questionnaire 6 weeks after the procedure. These 27 patients were
      matched for age, gender, and pre-procedure symptom score with patients in a
      prospectively gathered database of laparoscopic antireflux operations. Twenty-one
      patients (78%) in the endoscopic gastroplication group were satisfied with their
      symptomatic outcome, 2 (7%) were neutral, and 4 (15%) were dissatisfied. In
      comparison, there were 26 satisfied patients (96%) in the laparoscopic group ( <
      0.01). Median symptom scores improved similarly in both groups, with no
      statistically significant difference. The patients who were dissatisfied had a
      mean improvement in symptom score of 10, compared with 27 for the satisfied
      patients ( < 0.01). Endoscopic gastroplication is a viable alternative to
      laparoscopic fundoplication in selected patients. Nevertheless, approximately one
      quarter of patients will have no improvement, which is much more than those
      undergoing laparoscopic fundoplication.

PMID- 12193814
TI  - Control of port-site bleeding from smaller incisions after laparoscopic
      cholecystectomy surgery: a new, innovative, and easier technique.
AB  - Laparoscopic cholecystectomy has become the standard of care for patients with
      acute cholecystitis, symptomatic cholelithiasis, and biliary dyskinesia. Most
      surgeons now perform this procedure as outpatient surgery. In a standard
      laparoscopic cholecystectomy procedure, three trocar incisions are made outside
      the umbilicus. Stopping the bleeding from these port sites can be problematic
      because of the small size of the incision and the fact that these bleeding points
      are situated deep in the incision. This is especially true in obese patients and
      patients taking Asprin or Plavix and undergoing emergency cholecystectomy. In
      these circumstances, control of the bleeding requires either enlargement of the
      incision or placement of deep sutures, leading to an ugly scar. We present a
      simple and innovative technique for controlling port-site bleeding, which
      involves plugging the port-site hole with Surgicel (Johnson & Johnson Medical,
      Inc., Arlington, Texas). Our experience with 20 patients to date has shown wound
      healing to be excellent, with no complications such as hematoma or infection.

PMID- 12193815
TI  - Laparoscopic cholecystectomy in cirrhotic patients.
AB  - Since 1992, laparoscopic cholecystectomy has been the treatment of choice for
      symptomatic gallstones. The advantages of laparoscopic cholecystectomy for most
      patients have been extensively published. However, its benefits and successful
      use in patients with cirrhosis are less well documented. The aim of this study
      was to determine the efficacy and safety of laparoscopic cholecystectomy in
      cirrhotic patients. We did a retrospective review of the records of 26
      consecutive laparoscopic cholecystectomy procedures performed on cirrhotic
      patients between January 1992 and September 2000. Twenty-two patients were
      classified as having Child's class A cirrhosis, and 4 patients were classified as
      having Child's class B. No patients were classified as having Child's class C
      cirrhosis. There were 20 men and 6 women, with a mean age of 57 years (range, 37
      76). All procedures were completed laparoscopically. There was histologic
      confirmation of cirrhosis in all patients. The mean operative time was 126
      minutes (range, 60-184). The mean estimated blood loss was 110 mL (range, 40
      380). Complications occurred in 7 patients (27%). No operative mortality occurred
      in this study. The mean length of hospital stay was 5 days (range, 3-14). Our
      results and the results of others show that laparoscopic cholecystectomy in
      cirrhotic patients seems to be safe in selected Child-Pugh class A and B patients
      with compensated cirrhosis. Cholecystectomy remains a high-risk procedure in
      cirrhotic patients, and indications for cholecystectomy should be evaluated
      carefully. Controlled trials are required to confirm the safety of this
      procedure, and further studies are also required to evaluate the management of
      gallbladder disease in patients with Child-Pugh class C cirrhosis.

PMID- 12193816
TI  - Hand-assisted laparoscopic donor hepatectomy for living related transplantation
      in the porcine model.
AB  - Use of a minimally invasive approach for donor nephrectomy has proven to be safe
      and feasible and has increased the pool of donors for living related renal
      transplantation. A porcine study to assess the safety and feasibility of
      performing laparoscopic donor hepatectomy was performed, with potential
      application to human liver donors for living related liver transplantation. Of
      the 10 50-kg pigs used, 2 underwent an open left lateral segmentectomy to define
      the pig anatomy. Two subsequent pigs underwent a laparoscopic liver resection to
      refine the technique. Subsequently, under sterile conditions, six pigs underwent
      laparoscopic liver resection with use of a hand-assisted technique for long-term
      study. Diameters and lengths of hepatic vessels and ducts were measured.
      Operative blood loss, operative time, and warm ischemia duration were noted.
      Biopsies of the resected specimens were done to look for ischemia. There was one
      operative death in the group with chronic liver failure, due to stapler misfire
      and hemorrhage from the left hepatic vein. The only instance of morbidity was a
      wound infection. The resected liver had minimal warm ischemia time and
      microscopic changes, which led us to believe that the organ was suitable for
      transplantation. We believe that this long-term study establishes the feasibility
      of this procedure.

PMID- 12193817
TI  - Prospective comparison of laparoscopic versus open resection for benign
      colorectal disease.
AB  - Laparoscopic surgery is not being applied in a widespread manner in the
      management of benign or malignant colorectal disorders. This is a prospective
      comparison of 279 patients who underwent elective colorectal surgery. Colorectal
      diseases included inflammatory bowel, diverticular disease, colonic inertia,
      polyps, and rectal prolapse. Data included 136 patients who underwent
      laparoscopic surgery (mean age, 51.3 years) and 143 who underwent open surgery
      (mean age, 56.0 years). Thirteen patients' procedures were converted to open, but
      their results were included in the laparoscopic surgery group. There was no
      significant difference in operative time, postoperative complications, morbidity,
      or mortality between the laparoscopic and open surgery groups. More patients in
      the laparoscopic group had significant cardiac disease (6.0%, laparoscopic; 0.7%,
      open; = 0.01). More patients in the open group had undergone previous
      gastrointestinal surgery (3.7%, laparoscopic; 11.2%, open; = 0.02). The
      laparoscopic group used less postoperative analgesia and resumed oral feeding
      quicker ( < 0.05). In addition, time to first flatus and bowel movement was
      faster ( < 0.05), and the length of postoperative hospital stay (7.7 +/- 15.8
      versus 11.0 +/- 8.3; = 0.03) was shorter in the laparoscopic surgery group. There
      are significant advantages in postoperative recovery with the laparoscopic
      technique. If proven to be cost-effective, laparoscopic colorectal surgery for
      benign diseases should become the standard of surgical care.

PMID- 12193818
TI  - The effects of different hernia repair methods on postoperative pain medication
      and CRP levels.
AB  - Although tension-free techniques of hernia repair using synthetic meshes have
      yielded encouraging results, the best method of inguinal hernia repair is still
      unclear. The aim of this study was to compare the responses of inflammatory
      mediators and postoperative pain relief following laparoscopic total
      extraperitoneal (TEP) hernioplasty, open tension-free mesh hernioplasty
      (Lichtenstein), posterior preperitoneal mesh hernioplasty (Nyhus procedure), and
      Bassini procedure. Patients with primary inguinal hernia were randomized in the
      operating room to undergo one of these repair techniques. Group I comprised 24
      patients treated by Lichtenstein procedure; Group II comprised 21 patients
      treated by Nyhus procedure; Group III comprised 19 patients treated by Bassini
      procedure; and Group IV comprised 20 patients treated by laparoscopic TEP mesh
      hernioplasty. Postoperative pain levels following hernia repair were compared by
      measuring the use of patient-controlled analgesia (PCA) during the 24 hours after
      surgery. Serum samples withdrawn before surgery and 48 hours after surgery were
      assayed for C-reactive protein (CRP) content. Patient characteristics, operating
      time, and operative and early complications were noted. Serum CRP levels rose
      markedly following Nyhus (184.5 +/- 41.6 mg/L), Lichtenstein (138.4 +/- 72.5
      mg/L), and Bassini repair (137.2 +/- 55.9 mg/L) compared with that of patients
      who underwent TEP mesh hernioplasty (55.5 +/- 41.2 mg/L). There were also
      significant differences in the postoperative need for analgesics via PCA among
      patients undergoing Nyhus (382.9 +/- 189.1 mg), Bassini (303.2 +/- 173.7 mg), and
      Lichtenstein (253.9 +/- 129.3) procedures compared with 196.6 +/- 148.8 mg for
      the TEP mesh hernioplasty group. Patients in the Lichtenstein group also had
      significantly less need of analgesics than those in the Nyhus and Bassini groups.
      In conclusion, TEP mesh hernioplasty is less traumatic and yields less
      postoperative pain than the Nyhus, Lichtenstein, and Bassini procedures.

PMID- 12193820
TI  - A novel minimally invasive technique for insertion of peritoneal dialysis
      catheter.
AB  - The placement of a continuous ambulatory peritoneal dialysis (CAPD) catheter by
      conventional open surgical or trocar technique may cause a number of
      complications such as infection, hemorrhage, leakage, incisional hernia, and
      visceral organ perforation. Most complications are related to open surgery or
      insertion of the catheter with the guidewire without direct visualization.
      Insertion of the catheter laparoscopically under direct visualization has been
      previously described. The authors who described this technique used two or three
      ports for the camera and instruments. In this study we describe a laparoscopic
      technique for insertion of the peritoneal dialysis catheter under direct
      visualization with use of one-camera port and an accessory 2-mm umbilical
      incision. This prospective study was performed with the approval of the ethics
      committee of the Gazi University Hospital, in Ankara, Turkey. There were a total
      of eight patients: five males and three females, with an average age of 34.3
      years (range, 11-54), who underwent laparoscopic CAPD insertion between 1997 and
      2000. The catheter was inserted into the abdominal cavity 2 cm below the
      umbilicus. The subcutaneous tunnel was made with the assistance of a specially
      designed L-shaped trocar. All patients did well after the operation and had
      excellent cosmetic results. There was one leak in the early postoperative period,
      which was treated conservatively. The average operating time was 34.7 minutes
      (range, 25-45 minutes). The laparoscopic approach for peritoneal dialysis
      catheter insertion, for management of transmigrated CAPD catheters, and to
      resolve omental occlusions should be considered as an alternative to open
      surgery, especially for patients who have peritoneal adhesions secondary to a
      history of abdominal surgeries or recurrent peritonitis.

PMID- 12193819
TI  - Inhibition of tumor necrosis factor-alpha and inducible nitric oxide synthase
      correlates with the induction of IL-10 in septic rats undergoing laparotomy and
      laparoscopy.
AB  - Proinflammatory mediators are implicated in the mediation of host response to
      surgical stress. Greater inflammatory response has been reported after open
      surgery than after laparoscopic surgery in animal models. This study investigated
      the inflammatory response of tumor necrosis factor alpha (TNF) and inducible
      nitric oxide synthase (iNOS) and the anti-inflammatory response of interleukin
      (IL)-10 after laparotomy and laparoscopy in a rat endotoxic shock model. Rats
      received lipopolysaccharide (LPS) intraperitoneally and underwent laparotomy (n =
      5), laparoscopy (n = 5), or no surgical intervention (n = 5). A control group
      received anesthesia only (n = 5). Serum TNF levels peaked at 2 hours after LPS
      injection and were significantly suppressed in animals undergoing laparotomy and
      laparoscopy ( < 0.05). Serum IL-10 levels were higher at 2 hours in the
      laparotomy and laparoscopy groups but were higher only in the laparotomy group at
      4 hours after LPS injection ( < 0.05). Hepatic iNOS mRNA and protein were
      significantly inhibited at 4 and 8 hours in the laparotomy and laparoscopy groups
      in comparison with the animals receiving LPS only ( < 0.05). The induction of IL
      10 correlated with the suppression of TNF and iNOS suggests that IL-10 may play a
      role in downregulating TNF and iNOS in septic rats undergoing laparotomy and
      laparoscopy.

PMID- 12193821
TI  - Endoscopic thoracic sympathectomy for hyperhidrosis: experience with both
      cauterization and clamping methods.
AB  - The goal was to review results of sympathectomy, performed with use of either
      cauterization or clamping, in patients with hyperhidrosis (n = 1,312): 653 early
      patients undergoing electrocautery sympathectomy, 305 later patients undergoing
      cauterization, and 354 patients treated with a clamping procedure. Patients were
      interviewed by telephone about the status of symptoms, adverse outcomes, and
      satisfaction. Palmar hyperhidrosis was cured in all but one patient, with a 98%
      satisfaction rate in the clamping group and 94.3% and 95.1% in the two
      cauterization groups ( < or = 0.025, clamping > cauterization). Facial sweating
      or blushing was cured in the majority (88%) of the 301 patients reporting this
      symptom. Severe compensatory hidrosis occurred in less than 6% (3% of the
      clamping group; < or = 0.001, clamping < cauterization). Recurrence rate was
      3.0%. A number of factors were related to outcome. Endoscopic thoracic
      sympathectomy with clamping appears to be at least as safe and effective as
      earlier cauterization techniques, with the potential advantage of reversibility
      in those patients unhappy with the outcome.

PMID- 12193822
TI  - Hand-assisted D2 subtotal gastrectomy for carcinoma of stomach.
AB  - We report a case of hand-assisted D2 subtotal gastrectomy with Roux-en-Y
      reconstruction for advanced gastric cancer. This case shows the advantages of
      hand-assisted laparoscopic surgery for gastric cancer. Extended lymph node
      dissection and intracorporeal anastomosis are feasible and easier with the
      presence of the internal hand. Our method is an alternative to total laparoscopic
      radical gastrectomy.

PMID- 12193823
TI  - A case of ampullary carcinoma successfully managed with endoscopic snare
      resection.
AB  - Pancreaticoduodenectomy and transduodenal ampullectomy have been the procedures
      of choice for ampullary cancer in most patients. However, for patients with small
      ampullary neoplasms or who are unfit for laparotomy or refuse open surgical
      operations, endoscopic snare ampullectomy may be appropriate. We report here a
      case of ampullary carcinoma in which endoscopic snare ampullectomy was performed
      successfully, with long-term survival. The patient was a 77-year-old man with a
      30-year history of ulcerative colitis, who presented with epigastric pain and
      fever. He had a history of four laparotomies. Laboratory studies showed a mild
      elevation in alkaline phosphatase, serum aspartate aminotransferase, gamma
      glutamyltransferase, and C-reactive protein values. At endoscopic retrograde
      cholangiopancreatography, the ampulla was prominent, with granulomatous
      proliferation. The common bile duct was dilated to approximately 25 mm in
      diameter. Biopsy specimens of the ampulla showed a well-differentiated
      adenocarcinoma. Because of extensive adhesions of the peritoneal cavity due to
      the prior four laparotomies and the patient's refusal of surgery, endoscopic
      snare ampullectomy was performed. Ten days after the ampullectomy, the patient
      was discharged from the hospital without any complication. The patient has been
      well for the 4 years since then, without recurrence of the tumor or jaundice.
      Endoscopic snare ampullectomy may be considered as a viable alternative to
      surgery in patients with small ampullary tumors who are unfit for surgery or who
      prefer a nonsurgical approach.

PMID- 12193826
TI  - Experience with laparoscopic management of solitary symptomatic splenic cysts.
AB  - Aggressive laparoscopic procedures can be used to manage pathologic lesions of
      solid organs. We attempted laparoscopic management of solitary symptomatic
      splenic cysts in four patients--two men and two women--ranging in age from 19 to
      63 years (mean, 35 years). The cysts involved the whole spleen in one case, the
      upper pole in one, and the lower pole in two. We performed laparoscopic
      splenectomy in one case and laparoscopic unroofing of the cyst wall in three. In
      two procedures we successfully used needlescopic instruments. The duration of
      surgery and the volume of intraoperative bleeding were 300 minutes and 200 mL,
      respectively, for the splenectomy, and an average of 170 minutes (range, 120-240)
      and minimum volume, respectively, for the unroofing. There were no intra- or
      postoperative complications related to the laparoscopic procedures. The
      postoperative hospital stay was 9 days for the patient who underwent splenectomy
      and an average of 5.6 days (range, 5-7) for the patients who underwent unroofing.
      Laparoscopic management of splenic cysts is technically feasible and safe and has
      the advantages of reduced postoperative pain, shortened convalescence, and
      improved cosmesis.

PMID- 12193827
TI  - Elective laparoscopic splenectomy for grade III splenic injury in an athlete.
AB  - The safety and efficacy of laparoscopic splenectomy in the management of benign
      hematologic diseases is well established. Laparoscopic splenectomy for splenic
      trauma has been reported infrequently, and most consider a minimally invasive
      approach to be contraindicated. A heralded, standout college football player who
      sustained a grade III splenic laceration while playing football was referred for
      laparoscopic splenectomy so that he could convalesce rapidly, complete his final
      year of athletic eligibility, and prepare for the National Football League draft.
      The ethical issues regarding this patient's care were discussed extensively with
      the patient, his parents, and the hospital administration. After informed
      consent, the patient underwent a laparoscopic splenectomy with no intraoperative
      complications. He was discharged 20 hours after surgery. The patient played in a
      collegiate football game 12 days after surgery, was drafted into the National
      Football League 9 months later, and was on the opening day roster 12 months after
      his surgery. We do not advocate laparoscopic splenectomy for injuries to the
      spleen as the standard of care. This case, however, illustrates the potential for
      laparoscopic surgery to provide a safe and feasible alternative to traditional
      surgical approaches.

PMID- 12193829
TI  - Mechanical small bowel obstruction from a loose linear cutter staple after
      laparoscopic appendectomy.
AB  - Laparoscopic linear cutting staplers are commonplace in advanced laparoscopic
      techniques. Most of the loose staples are probably inert, but we present a case
      of a mechanical small bowel obstruction after a laparoscopic appendectomy. The
      etiology of the bowel obstruction was a loose linear cutter staple from the load
      that fired across the appendiceal stump. We recommend retrieving as many loose
      staples as possible with the laparoscopic grasper or suction at the termination
      of the laparoscopy.

PMID- 12193830
TI  - Laparoscopically assisted reversal of Hartmann's procedure revisited.
AB  - Reversal of Hartmann's procedure is a major operation, associated with
      substantial morbidity and mortality. In light of this, many patients elect not to
      undergo reversal (44-49%). In recent years, enthusiasm for laparoscopic reversal
      of Hartmann's procedure has increased, with the outcomes of many series
      suggesting that it has a reduced morbidity and mortality compared with the open
      procedure. We present our initial experience of four cases of laparoscopically
      assisted reversal of Hartmann's procedure and review the literature on this
      technique. Laparoscopic reversal was successful in all but one case. Literature
      review shows reduced postoperative hospital stay compared with the traditional,
      open approach and suggests that laparoscopic reversal is associated with lower
      morbidity and mortality rates. Laparoscopic reversal of Hartmann's procedure is
      feasible with potential advantages for the patient.

PMID- 12193831
TI  - Thoracoscopy: the preferred method for excision of mediastinal parathyroids.
AB  - Mediastinal exploration to resect ectopic parathyroid is required in
      approximately 2% of all cases of hyperparathyroidism. Traditionally, it has been
      performed through a midsternotomy or thoracotomy. A few reports about
      thoracoscopic resection of mediastinal parathyroid were published recently. We
      report here successful video-assisted thoracoscopic resection (VATS) of a
      mediastinal parathyroid and present a review of all previously reported cases. A
      42-year-old woman presented with spontaneous fracture of the left femur and
      hypercalcemia. She had previously undergone cervical parathyroidectomy for
      primary hyperparathyroidism. A computed tomography (CT) scan of the chest and a
      technetium scan showed ectopic mediastinal parathyroid. The patient underwent
      successful thoracoscopic resection of ectopic parathyroid. A total of 26 patients
      were reviewed, 21 in the English literature and 5 in others. Of the 21 patients
      reported in the English literature, 16 had primary hyperparathyroidism (1 degrees
      HPT), whereas 5 had secondary hyperparathyroidism (2 degrees HPT). All but 3
      patients had undergone previous cervical exploration. Ectopic mediastinal
      parathyroid was localized preoperatively in all by CT scans of the chest and
      nuclear scans. All 21 patients had successful thoracoscopic resection. All but 3
      had parathyroid adenoma. Postoperatively, serum calcium (Ca ), phosphate (PO4 ),
      and parathormone (PTH) values returned to normal in all patients. Age and sex of
      the patient, type of hyperparathyroidism (1 degrees or 2 degrees ), size of the
      gland, its location within the anterior mediastinum, the approach used to resect
      it (right or left thoracoscopic), and final histopathology of the resected gland
      (adenoma or hyperplasia) had no bearing on the success of thoracoscopic
      resection. The data seem to suggest that thoracoscopic resection of mediastinal
      parathyroid is a less-invasive, effective, and safe procedure. Accurate
      preoperative anatomic localization by CT and nuclear scans of the chest is the
      key to success.

PMID- 12193832
TI  - Needlescopic appendectomy as a routine procedure: "Just because you can?" or
      "Just because you cannot?".

PMID- 12193833
TI  - Quality of life 2 years after laparoscopic total fundoplication.

PMID- 12193834
TI  - Hypochondriasis and fear of death.
AB  - Although fear of death has been linked to hypochondriasis, the relationship of
      this fear to the disorder has received little study. To address this deficiency,
      we administered a fear of death scale along with measures of hypochondriasis,
      including the Whiteley Index and Somatic Symptom Inventory, to 162 general
      medical outpatients. Partial correlations, controlling for age, between the fear
      of death scale and both the Whiteley Index and Somatic Symptom Inventory were
      strongly positive. A factor analysis of the fear of death scale yielded three
      dimensions-fear of dying, loss of meaning, and fear of separation-that were also
      highly correlated with hypochondriasis. Fear of death and hypochondriasis showed
      comparable relationships to age and gender as well as to personality dimensions
      measured by the NEO Five-Factor Inventory. Fear of death appears to be an
      integral part of hypochondriasis. Its presence lends support to three models of
      hypochondriasis-the perceptual, existential, and interpersonal-that correspond to
      the dimensions of fear of death.

PMID- 12193835
TI  - Traumatic exposure and posttraumatic stress disorder in borderline, schizotypal,
      avoidant, and obsessive-compulsive personality disorders: findings from the
      collaborative longitudinal personality disorders study.
AB  - The association between trauma and personality disorders (PDs), while receiving
      much attention and debate, has not been comprehensively examined for multiple
      types of trauma and PDs. The authors examined data from a multisite study of four
      PD groups: schizotypal, borderline (BPD), avoidant, and obsessive-compulsive, and
      a major depression comparison group. Rates of traumatic exposure to specific
      types of trauma, age of first trauma onset, and rates of posttraumatic stress
      disorder are compared. Results indicate that BPD participants reported the
      highest rate of traumatic exposure (particularly to sexual traumas, including
      childhood sexual abuse), the highest rate of posttraumatic stress disorder, and
      youngest age of first traumatic event. Those with the more severe PDs
      (schizotypal, BPD) reported more types of traumatic exposure and higher rates of
      being physically attacked (childhood and adult) when compared to other groups.
      These results suggest a specific relationship between BPD and sexual trauma
      (childhood and adult) that does not exist among other PDs. In addition, they
      support an association between severity of PD and severity of traumatic exposure,
      as indicated by earlier trauma onset, trauma of an assaultive and personal
      nature, and more types of traumatic events.

PMID- 12193836
TI  - Insight, global neuropsychological functioning, and symptomatology in chronic
      schizophrenia.
AB  - It is proposed that poor insight in schizophrenia may be explained by
      neuropsychological dysfunction and linked to the negative syndrome, which in turn
      may be related to structural neurological impairment. This study tested the
      hypothesis that poor insight is related to global neuropsychological impairment
      and negative symptoms in 89 patients with chronic schizophrenia. No significant
      association was found between total insight and cognitive impairment. When the
      dimensions of insight-treatment compliance, awareness of illness, and symptom
      attribution-were analyzed separately, symptom misattribution was modestly
      correlated with frontal impairment. However, in subsequent multiple regression
      analyses, cognitive impairment failed to be a significant predictor of this or
      any other dimension of insight. Symptoms, particularly positive ones, accounted
      for approximately one quarter of the variance in symptom misattribution and the
      total insight score. These results suggest that neuropsychological functioning
      cannot account for the variance in insight, and that only one quarter of the
      variance in symptom misattribution can be explained by symptomatology. Future
      research could also address the role of psychosocial factors in modulating the
      expression of insight.

PMID- 12193837
TI  - Summer birth and deficit schizophrenia: Cantabria, Spain.
AB  - An association between deficit schizophrenia and summer birth has previously been
      reported. The authors attempted to replicate this association in a population
      based study of incident cases of psychosis in the autonomous region of Cantabria,
      in northern Spain. Schizophrenia patients were categorized into deficit (N = 22)
      and nondeficit (N = 55) groups, and the pattern in the two groups was compared.
      After accounting for the variance due to disorganization, hallucinations and
      delusions, and demographic variables, deficit schizophrenia had a significant
      association with summer birth; this association did not depend on a single
      definition of summer. For instance, among the deficit patients, 59% were born
      from May to August, in contrast to 18% of nondeficit patients and 34% of the
      general population. These results confirm the association between summer birth in
      the Northern Hemisphere and deficit as opposed to nondeficit schizophrenia. The
      existence of a different risk factor for the two groups suggests a difference in
      etiology and pathophysiology.

PMID- 12193838
TI  - Experimental facilitation of the sensed presence: possible intercalation between
      the hemispheres induced by complex magnetic fields.
AB  - This experiment was designed to test the hypothesis that the sensed presence, the
      feeling of a proximal sentient being, can be evoked within the laboratory. Under
      double-blind conditions, 48 university men and women were exposed to weak (100 nT
      to 1 muT), complex, pulsed magnetic fields that were applied primarily over the
      right temporoparietal region, primarily over the left temporoparietal region, or
      equally across both hemispheres (one treatment per group) for 20 minutes while
      wearing opaque goggles in a very quiet room. A fourth group was exposed to a sham
      field condition. Subjects who received greater stimulation over the right
      hemisphere or equal stimulation across both hemispheres reported more frequent
      incidences of presences, fears, and odd smells than did the subjects who received
      greater stimulation over the left hemisphere or who were exposed to the sham
      field condition. The results suggest that the sensed presence is subject to
      experimental manipulation. This experimental procedure could be employed to
      explore the idea that the experience of a sensed presence is a resident property
      of the human brain and may be the fundamental source for phenomena attributed to
      visitations by gods, spirits, and other ephemeral phenomena.

PMID- 12193839
TI  - Computerized content analysis of some adolescent writings of Napoleon Bonaparte:
      a test of the validity of the method.
AB  - The aim of this study was to test the validity of a computer software program
      previously demonstrated to be capable of making DSM-IV neuropsychiatric diagnoses
      from the content analysis of speech or verbal texts. In this report, the computer
      program was applied to three personal writings of Napoleon Bonaparte when he was
      12 to 16 years of age. The accuracy of the neuropsychiatric evaluations derived
      from the computerized content analysis of these writings of Napoleon was
      independently corroborated by two biographers who have described pertinent
      details concerning his life situations, moods, and other emotional reactions
      during this adolescent period of his life. The relevance of this type of computer
      technology to psychohistorical research and clinical psychiatry is suggested.

PMID- 12193841
TI  - Co-occurrence of DSM-IV personality disorders with borderline personality
      disorder.

PMID- 12193840
TI  - Current progress in schizophrenia research: sensory gating deficit in
      schizophrenia: is the nicotinic alpha-7 receptor implicated?

PMID- 12193842
TI  - Understanding ambulatory care use by people with panic attacks: testing the
      behavioral model for vulnerable populations.

PMID- 12193843
TI  - Religious psychiatry: the Canadian experience.

PMID- 12193844
TI  - Electroencephalography during sleep of patients with nocturnal panic disorder.

PMID- 12193845
TI  - Cocaine abuse in the elderly: a series of three case reports.

PMID- 12193846
TI  - Interactions of psychological factors and family history in relation to coronary
      artery disease.
AB  - BACKGROUND: Psychological factors including hostility, depression and stress have
      been associated with severity of coronary artery disease (CAD). However, few
      studies have examined interactions between such factors and typical CAD risk
      factors. Investigating interactive effects simulates their co-occurrence and
      complex effects in illness, as well as helping to identify groups of patients at
      greatest risk of morbidity. This study examined the interactive effects of
      hostility, hopelessness and daily hassles with family history of CAD in relation
      to CAD severity. DESIGN: Correlation design. METHODS: Seventy-three patients were
      assessed for hostility, hopelessness and daily hassles before undergoing coronary
      artery angiography. Severity of CAD was assessed by a cardiologist who was blind
      to patients' psychological data, with a scale considering type and proximity of
      occluded artery: the Ilia-score. RESULTS: Hostility significantly interacted with
      family history in relation to CAD severity. Hostility was positively correlated
      with CAD severity when family history was positive (r = 0.43, P< 0.05), but not
      when family history was absent (r = -0.10, NS). No other interaction effects were
      found. Interestingly, patients with family history of CAD had significantly lower
      hostility scores (14.4) compared to patients without such history (19.2; P=
      0.002). No background or typical-risk factor correlated with CAD severity.
      CONCLUSION: Hostility synergistically interacted with family history of CAD in
      relation to CAD severity. The mechanisms of this interaction need to be explored
      in future studies. Hostility-reduction interventions provided to high-hostile
      patients with a genetic predisposition to CAD may be relevant for primary and
      secondary CAD prevention.

PMID- 12193847
TI  - Aortic valve calcium on spiral computed tomography (dual slice mode) is
      associated with advanced coronary calcium in hypertensive patients.
AB  - BACKGROUND: Aortic valve calcium (AVC) is common in the elderly and is associated
      with an increase risk of death from cardiovascular causes and of myocardial
      infarction. The goal of the present study was to determine whether an association
      exists between the presence of AVC and coronary calcium (CC) in high-risk
      hypertensive patients as detected by spiral computed tomography (dual slice mode)
      (DHCT). DESIGN AND METHODS: Three hundred and seventy-six hypertensive patients
      participating in the International Nifedipine Gastrointestinal Therapeutic System
      (GITS) Study of Intervention as a Goal in Hypertension Treatment (INSIGHT) in our
      region were included (197 men and 179 women, age range 55-79 years). All
      underwent DHCT of the heart for CC scoring using previously published methods. A
      positive test for the presence of CC was defined as the presence of at least one
      lesion with an area of 0.5 mm and DHCT density above 90 Hounsfield units (total
      CC score >0). CC was considered advanced when total calcium score was >300. AVC
      was defined by DHCT as any detected calcified deposit in the region of the aortic
      valve. Patients without AVC served as the control group. RESULTS: AVC was
      documented in 70 patients (36 men, 34 women; mean age 66 +/- 5 years, range 57-79
      years). The age- and sex-matched non-AVC group (control group) included 306
      patients (161 men, 145 women; mean age 67 +/- 5 years, range 55-75 years). There
      were no intergroup differences in risk factors for atherosclerosis. Significant
      differences were found between AVC and the control groups for mean CC score (388
      +/- 754 compared with 147 +/- 307, P< 0.001) and between the presence of advanced
      CC and the control group (27 compared with 15%, P= 0.02). Significant differences
      were also found for the presence of three-vessel calcification (36 compared with
      21%, P= 0.01) and the number of vessels involved (1.8 +/- 1.1 compared with 1.4
      +/- 1.1, P= 0.01). Stepwise logistic regression found age [odds ratio (OR) 1.08,
      95% confidence intervals (CI) 1.03-1.15), gender (OR 0.45, 95% CI 0.25-0.82) and
      AVC (OR 2.07, 95% CI 1.06-4.02)] to be the only variables that predict advanced
      CC. CONCLUSIONS: Our study demonstrated a significant association between the
      presence of AVC and advanced CC on spiral computed tomography. These results
      strengthen earlier findings of a high association between AVC and increased risk
      of death from cardiovascular causes.

PMID- 12193848
TI  - Time course of plasma adhesion molecules in acute coronary syndromes.
AB  - BACKGROUND: Atherosclerosis is an inflammatory process in which adhesion
      molecules play an intimate role in both the initiation and progression of
      lesions. It is postulated that they also play a role in the presentation of acute
      coronary syndromes and that plasma levels thereafter may be of potential
      prognostic significance. The stability of sample levels under different
      laboratory conditions is unknown. METHODS: Stability of plasma levels was
      assessed in six healthy subjects under four different laboratory conditions. The
      time course of levels was studied in 57 patients with acute chest pain, 21 of non
      cardiac aetiology, 23 unstable angina and 13 acute myocardial infarction, at mean
      times of 2.3, 8.2 and 17.3 h after the onset of pain. Samples were assayed for
      intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1
      (VCAM-1), P-selectin, E-selectin and C-reactive protein (CRP). RESULTS: ICAM-1,
      VCAM-1, P-selectin and E-selectin levels did not differ under different
      laboratory conditions. Levels were similar at presentation in patients with acute
      chest pain of non-cardiac aetiology, unstable angina or acute myocardial
      infarction (median levels ICAM-1 269 microg/l, VCAM-1 379 microg/l, P-selectin
      167 microg/l and E-selectin 53 microg/l). Levels did not change in the 24 h
      following the onset of pain. CRP levels did not differ at presentation between
      groups (median level 2.1 mg/l), but rose more than 12 h after the onset of pain
      in the group with acute myocardial infarction (P < 0.05). CONCLUSION: Adhesion
      molecule levels are stable under normal laboratory sample handling conditions.
      Levels do not change in the 24 h following the onset of chest pain of non-cardiac
      or acute ischaemic aetiology.

PMID- 12193849
TI  - Dipyridamole myocardial perfusion single photon emission computed tomography in
      patients with slow coronary flow.
AB  - OBJECTIVE: Several studies have indicated that the velocity of contrast dye
      increases after intravenous dipyridamole infusion in patients with a slow-flow
      pattern (SFP). In this study we compared the results of coronary arteriography
      and exercise myocardial perfusion single photon emission computed tomography
      (SPECT) in patients with SFP. We also investigated the changes in myocardial
      perfusion in patients with abnormal exercise myocardial perfusion SPECT by using
      a pharmacological stress test with dipyridamole. DESIGN AND PATIENTS: This study
      included 60 patients who revealed SFP in their coronary arteriograms. Slow
      coronary flow diagnoses were made using the frame count method. A single day rest
      exercise technetium-99m hexakis-2-methoxy-isobutyl isonitrile (Tc-99m MIBI; Du
      Pont Pharma SA, Belgium) SPECT was performed in all patients. Patients who had
      reversible perfusion defect (RPD) on the exercise SPECT were evaluated with
      dipyridamole myocardial perfusion scintigraphy. RESULTS Patients with SFP
      revealed both higher frame counts in native coronary arteries and higher mean
      frame counts. The coronary frame count was 26.4 +/- 3.5 in control patients and
      64.40 +/- 16.64 in patients with SFP, respectively (P < 0.001). Exercise
      perfusion SPECT showed RPD in 17 patients (group 1), but was normal in 43 others
      (group 2). There were no statistically significant differences between groups 1
      and 2 in frame counts. Myocardial perfusion was normalized in all 17 patients of
      group 1 after dipyridamole infusion. CONCLUSIONS: In patients with SFP perfusion,
      changes may improve with dipyridamole infusion. This study indicates that this
      improvement can be shown by dipyridamole SPECT. Furthermore, no correlation was
      observed between the time needed to fill a native coronary artery and RPD of the
      myocardium.

PMID- 12193850
TI  - Clinical and angiographical characteristics of acetylcholine- induced spasm:
      relationship to dose of intracoronary injection of acetylcholine.
AB  - OBJECTIVES: The purpose of this study was to clarify clinical and angiographical
      characteristics of acetylcholine (ACh)-induced spasm in the right and left
      coronary artery. METHODS AND RESULTS: We performed 557 consecutive procedures of
      spasm provocation tests of ACh from January 1991 to December 2000 in patients
      without significant stenosis. ACh was injected in incremental doses of 20, 50 and
      80 microg into the right coronary artery and in incremental doses of 20, 50 and
      100 microg into the left coronary artery if spasm had not been provoked. Coronary
      spasm was defined as positive with more than 99% transient luminal narrowing.
      Proximal spasm was defined as that of segments 1, 2, 5, 6, 7 and 11 and distal
      spasm as that of segments 3, 4, 8, 9, 12, 13 and 14. Low-ACh-dose-induced spasms
      showed the clinical findings and angiographical characteristics of higher
      incidence of variant angina, proximal spasms, focal spasms, more ST elevation and
      ischemic heart disease. In contrast, angiographical characteristics of high-Ach
      dose-induced spasms were distal spasms and diffuse spasms and there was less
      variant angina and less ST elevation. CONCLUSIONS: Lower ACh doses induced spasms
      more proximally and focally in the coronary artery, while higher doses of ACh
      provoked spasms more distally and diffusely.

PMID- 12193851
TI  - In-vivo biocompatibility evaluation of stents coated with a new biodegradable
      elastomeric and functional polymer.
AB  - BACKGROUND: In-stent restenosis may be prevented by impregnating an
      antiproliferative agent in a polymer from a stent platform. This approach
      requires both an antiproliferative agent effective in small doses and a
      biocompatible polymer. METHODS: A series of new biodegradable elastomeric
      poly(ester-amide)(co-PEA) polymers having functional carboxyl groups for drug
      conjugation were synthesized from non-toxic building blocks. The in-vivo
      biocompatibility was tested in porcine coronary arteries, by comparing the
      polymer-coated stents with bare metal stents in 10 pigs. RESULTS: All animals
      survived until sacrifice 28 days later and follow-up angiography prior to
      sacrifice revealed identical diameter stenosis (21 +/- 23%) in both groups.
      Histology confirmed similar injury scores (0.34 +/- 0.34 compared with 0.34 +/-
      0.32), inflammatory reaction (1.18 +/- 0.38 compared with 1.11 +/- 0.32) and area
      stenosis (26 +/- 17% compared with 28 +/- 22%). CONCLUSIONS: This study suggests
      that the newly developed copoly(ester-amide) elastomers may be suitable for stent
      based local drug delivery.

PMID- 12193852
TI  - Differential efficacy of different platelet glycoprotein IIb/IIIa antagonists on
      platelet/fibrin-mediated clot dynamics under different conditions using
      thrombelastography: the critical need for anticoagulant.
AB  - BACKGROUND: Intravenous GpIIb/IIIa antagonists demonstrate various significant
      clinical benefits depending on the agent used. In contrast, oral delivery of
      GpIIb/IIIa antagonists failed in achieving clinical benefits. This raises the
      question about the differences among different GpII/IIIa antagonists. METHODS:
      The effect of various platelet glycoprotein (GP) IIb/IIIa antagonists on the
      dynamics of platelet/fibrin clot formation and strength was determined using
      thrombelastography under different conditions. RESULTS: GPIIb/IIIa antagonists
      with high affinity for resting and activated platelets and with slow rates of
      dissociation from GPIIb/IIIa (Class I antagonists) demonstrated potent and
      comparable inhibition of platelet aggregation and platelet-mediated clot strength
      under different conditions. In contrast to antagonists that dissociate rapidly
      from GPIIb/IIIa (class II antagonists). Class I antagonists such as the free acid
      form of roxifiban inhibited platelet-mediated clot strength, with the inhibiting
      concentration required for 50% effect (IC50) = 70 n mol/l, whereas the IC50 of
      the class II antagonists such as the free acid forms of orbofiban, sibrafiban,
      lotrafiban, integrilin or aggrastat ranged from 1 to 15 micromol/l. The IC50s for
      class II antagonists in inhibiting platelet/fibrin clot formation and strength
      were substantially greater (10-15 fold) than their clinically achievable
      concentrations. The limited efficacy for class II antagonists in inhibiting
      platelet-mediated clot dynamics was enhanced by the combination with heparin.
      CONCLUSIONS: Thus, these data indicated that there are differences in the
      efficacy of various GPIIb/IIIa antagonists in inhibiting platelet/fibrin clot
      formation and strength, which might be corrected by heparin. Data also suggest
      that inhibition of platelet aggregation may not be the sole determinant for the
      in-vivo efficacy of various GPIIb/IIIa antagonists.

PMID- 12193853
TI  - [Towards early screening and treatment of hepatocellular carcinoma cirrhosis?].

PMID- 12193854
TI  - [The molecular genetics of hematochromatosis].

PMID- 12193855
TI  - [Practical screening and early treatment of hepatocellular carcinoma. Results of
      a French survey].
AB  - AIM: To describe French practices for screening hepatocellular carcinoma.
      METHODS: A standardized questionnaire was mailed to all French hospital hepato
      gastroenterologists in June 1999. RESULTS: 411 out of 623 practitioners responded
      (66%). 394 (96%) routinely screen hepatocellular carcinoma, mainly with
      ultrasound (98%) and mainly at 6-month intervals (77%). Screening was performed
      in cirrhosis (100%) or extensive fibrosis (54%), independent of the etiology
      (21%) or the Child-Pugh score of the chronic liver disease (41%), but based on
      age and treatment feasibility. If of a small hypoechogenic nodule was detected in
      a young patient with compensated HCV-cirrhosis, 59% of practitioners performed a
      histological examination. In case of non biopsy-proven hepatocellular carcinoma,
      a second biopsy (49%), treatment (either percutaneous alcohol injection,
      resection or transplantation) (24%) or an ultrasonographic follow-up (23%) was
      proposed. In case of biopsy-proven hepatocellular carcinoma, resection (49%),
      transplantation (30%) or percutaneous alcohol injection (16%) was proposed.
      CONCLUSION: Almost all French specialists routinely screen cirrhotic patients for
      hepatocellular carcinoma, but use somewhat different modalities. In case of small
      HCC without contraindications to curative treatment, surgical resection is
      performed in half the patients.

PMID- 12193857
TI  - [Study of the antiviral mechanism of action of ribavirin in the bovine viral
      diarrhea virus model].
AB  - AIM: Due to the absence of a cell culture model for HCV, this study evaluated the
      hypothesis of lethal mutagenic activity of the guanosin analogue ribavirin in
      HCV, using the BVDV model. METHODS: First the capacity of ribavirin to inhibit
      BVDV replication in cell culture was studied. We then amplified by RT-PCR the
      5'NTR and NS5B regions of BVDV in the supernatants of BVDV-infected cell cultures
      treated with increasing concentrations of ribavirin. The PCR products were then
      sequenced to detect potential mutations. RESULTS: At a phenotypic level, the
      inhibition of BVDV replication by ribavirin was most potent when ribavirin was
      administered soon after BVDV inoculation. These results show a direct antiviral
      effect of ribavirin on BVDV at an early stage of the viral cycle. At a genotypic
      level, ribavirin decreased viral RNA levels. CONCLUSION: This study shows that
      ribavirin directly inhibits BVDV replication. These results could explain the
      synergistic effect of ribavirin and IFN in combined therapy in chronic carriers
      of HCV. This effect must be confirmed with subgenomic replicons of HCV.

PMID- 12193856
TI  - [Split-liver transplantation in two adult recipients: evaluation of feasibility
      in 100 consecutive cadaver liver grafts].
AB  - AIM: To evaluate the feasibility of splitting a liver graft for transplantation
      in two adult patients. PATIENTS AND METHODS: We retrospectively collected data on
      the harvesting of 100 consecutive liver grafts. Data were separated into 4 groups
      to establish feasibility criteria, according to the chronological steps of
      harvesting: 1) initial criteria about the donor (age, weight, biological tests),
      2) criteria concerning the liver graft at the time of harvesting (macroscopic
      appearance, graft weight, hemodynamic state of donor), (3) anatomical criteria
      and (4) histological criteria. RESULTS: If our criteria for the feasibility of
      splitting a liver graft for transplantation in two adults had been applied, 47
      grafts would have been rejected based on initial criteria, 34 at the time of
      harvesting and 6 because of anatomical or histological evaluation. Finally, 13
      liver grafts would have been accepted for splitting and then transplantation in
      two adults. CONCLUSIONS: Split-liver transplantation for two adult recipients
      could increase the graft pool by 13%. This procedure requires technical changes
      in organ harvesting and coordination among centers.

PMID- 12193858
TI  - [Transplantation of isolated hepatocytes. Principles, mechanisms, animal models,
      clinical results].

PMID- 12193859
TI  - [Changes in chemotherapy for pancreatic adenocarcinoma].

PMID- 12193860
TI  - [5-FU, folinic acid and cisplatin (LV5FU2-P) for unresectable pancreatic cancer].
AB  - AIM: To prospectively evaluate efficacy and tolerance of the 5-fluorouracil +
      folinic acid + cisplatin (LV5FU2-P) combination in the treatment of unresectable
      pancreatic carcinoma. PATIENTS AND METHODS: Between March 1998 and June 2000, 35
      patients, mean age 61 years (37-75), with advanced (n=2) or metastatic (n=33)
      pancreatic cancer and initial performance status (WHO) of 0 (n=9), 1 (n=14) or 2
      (n=12) were enrolled in the study. Two consecutive groups of patients were
      treated twice monthly, the first group (n=19) received the LV5FU2 regimen: a 2
      hour-infusion of leucovorin 200 mg/m(2), 5-FU bolus 400 mg/m(2), followed by 22
      hour continuous infusion of 5-FU 600 mg/m(2) on 2 consecutive days and cisplatin
      50 mg/m(2) on day 2. The second group (n=16) received a simplified schedule with
      bolus leucovorin 40 mg/m(2), 5-FU bolus 400 mg/m(2) on day 1, followed by 5-FU
      2400 mg/m(2) 48-hour infusion and cisplatin 50 mg/m(2) on day 2. Clinical
      symptoms and performance status were monitored together with weight changes.
      Tumor assessment was performed every 2 months. RESULTS: Three patients (9%)
      exhibited grade 4 neutropenia and grade 3 toxicity occurred in 31% of the
      patients (neutropenia: n=3, thrombocytopenia: n=1, vomiting: n=3, mucositis: n=3,
      diarrhea: n=1). There were no treatment-related deaths. Objective response was
      observed in 10 patients (29%, 95% confidence interval: 20-40%) including one
      complete response. Median progression-free survival and overall survival were 4.5
      and 9 months, respectively. Six-months and 1-year survival rates were 70% and
      25%, respectively. Weight gain was observed in 40% of the patients and
      performance status improved in 50%. CONCLUSION: LV5FU2-P regimen is active and
      well tolerated. It should be compared to gemcitabine as a first line therapy in
      advanced and metastatic pancreatic cancer.

PMID- 12193861
TI  - [Correlation of histological classifications of gastric carcinomas with location
      and prognosis].
AB  - AIM: To evaluate the prognostic impact of different histological classifications
      of gastric adenocarcinoma. METHODS: Between 1993-2000, 94 patients with gastric
      adenocarcinoma were studied. Tumors were classified according to TNM staging,
      WHO, Lauren and Goseki classifications. Twenty five patients (27%) had a proximal
      tumor and 69 (73%) a distal tumor. Intestinal type according to Lauren were more
      often observed among the proximal carcinomas (19/25) than in distal ones (32/69)
      (P=0.01). According to Goseki, lymph node metastasis were less frequently found
      in group III (5/13) than in other groups (64/81) (P=0.033). The mean follow-up
      was 23 months. Survical was not influenced by WHO, Lauren, and Goseki
      classifications. Survival significantly varied according to the different groups
      of the TNM classification. The proximal location of the tumor was associated with
      poorer prognosis than distal location (P=0.0373). Number of metastatic lymph
      nodes, invasion of perineurium, and vascular invasion had significant prognostic
      value in proximal carcinomas. CONCLUSION: The results of this study suggest that
      gastric carcinomas should be divided into proximal and distal tumors using the
      Goseki classification in addition to the Lauren classification because the Goseki
      classification recognizes tumor groups with different dissemination routes.

PMID- 12193863
TI  - [Role of enteric infections and inflammation in functional bowel disorders].

PMID- 12193862
TI  - [Undiagnosed celiac disease in childhood].
AB  - AIMS: This study was designed to assess the proportion of adult patients with
      celiac disease who had had undiagnosed symptoms during childhood and to determine
      the consequences of such diagnostic delay. PATIENTS AND METHODS: One hundred
      eighty-four patients with celiac disease (56 males, 128 females, age range 17-88
      years) were classified according to diagnosis and symptoms of celiac disease
      during childhood. Prevalence of short stature, low fertility, clinical
      osteoporosis, cancer, and autoimmune disease were assessed in each celiac group
      and compared with a control group matched for gender and age. RESULTS: Compared
      with the control group, patients with celiac disease were shorter (men 171.4 +/-
      9.0 cm vs 176.4 +/- 6.9 cm, P<0.01; women 159.7 + 7.3 cm vs 162.7 +/- 6.2 cm,
      P<0.01) and had a higher prevalence of symptomatic osteoporosis (5%) cancer
      (10%), and autoimmune disease (25%). Compared with matched controls and with
      patients whose celiac disease had been diagnosed during childhood (n=36), or who
      had remained symptom-free (n=95), patients who had undiagnosed symptomatic celiac
      disease during childhood exhibited higher prevalence of short stature (26%), low
      female fertility or low birth weight (36%). Multivariate analysis showed that
      short stature and low fertility correlated with duration of symptoms before
      diagnosis; osteoporosis and cancer correlated with age. The prevalence of
      autoimmune disease was unrelated to early onset of symptoms or delay to
      diagnosis. CONCLUSIONS: Missing the diagnosis of celiac disease in a symptomatic
      child may lead to short stature and low female fertility.

PMID- 12193864
TI  - [Intraperitoneal migration of Filshie tubal sterilization clips: an uncommon
      cause of chronic abdominal pain].
AB  - Tubal clips for female sterilization account for about 10 to 40% of the
      contraceptive methods used throughout the world. Clip migration is an unusual
      complication which may lead to chronic unexplained abdominal pain. We report here
      the case of a 44-year-old woman who suffered from chronic abdominal pain. The
      diagnosis of intraperitoneal migration of the Filshie clip fixed five years
      earlier was made. Cure was achieved with ablation of the clip. Late complications
      of Filshie clips are uncommon and non-specific. They include tubal necrosis and
      section, sterilization failure (0.7%), and migration (0.6%). Rare migrations into
      the bladder, the peritoneum, the appendix, or the vagina have been reported. When
      investigating chronic abdominal pain in a female patient, the clinician should
      inquire about sterilization history and carefully examine plain x-rays of the
      abdomen in women with tubal clips.

PMID- 12193865
TI  - [Groove pancreatitis: a rare segmental form of chronic pancreatitis].
AB  - Groove pancreatitis is a rare form of segmental chronic pancreatitis which is
      localized within the head of the pancreas, the duodenum and the common bile duct.
      Symptoms are due to common bile duct stenosis or duodenal stenosis.
      Radiologically, there is a pancreatic mass, which hinders differential diagnosis
      with pancreatic carcinoma. We report here a case of groove pancreatitis observed
      in a 41-year-old man treated by pancreatoduodenectomy. Histological features of
      the groove scar were noted. Our case and cases reported in the literature lead to
      hypotheses concerning the pathogenesis and clinical, biological, and radiological
      features suggestive of the diagnosis.

PMID- 12193866
TI  - [Management of hereditary hemochromatosis by gastroenterologists in general
      hospitals. Results of a National Association of Gastroenterologists study].

PMID- 12193867
TI  - [Amlodipine-induced acute hepatitis].

PMID- 12193868
TI  - [Hydropneumothorax complicating sqamous-cell esophageal carcinoma].

PMID- 12193869
TI  - [Prolonged prothrombin time: don't overlook amyloidosis].

PMID- 12193870
TI  - [Duodenal obstruction by balloon of replacement tube of percutaneous endoscopic
      gastrostomy].

PMID- 12193871
TI  - [Training programs for hepatogastroenterologists in Europe].

PMID- 12193872
TI  - [Central role of epidermic growth factor receptor (EGFR) in hypertrophic
      gastropathy and cancer of the colon].

PMID- 12193873
TI  - [Radioguided surgery for primary hyperparathyroidism: 100 cases].
AB  - One hundred patients with primary hyperparathyroidism underwent radioguided
      surgery within 90 to 180 minutes following IV injection of a diagnostic dose of
      MIBI and after parathyroid scanning with planar and oblique views. Exclusion
      criteria were thyroid pathology requiring surgery and suspicion of multiple
      endocrine neoplasia. A>20% step-up between the background noise and tissue uptake
      was the diagnostic threshold for parathyroid hyperfunctionning tissue, and this
      was observed in only 15% of cases overall all cured, but two. This method of
      detection is technically demanding and various angles of application of the probe
      can result in significant discrepancies of recorded uptake for the same spot. Our
      results demonstrate a physiological step-up between the ipsilateral unaffected
      upper and lower quadrants of the neck (range: - 34% to - 5%), seemingly because
      of the proximity of supra-aortic vessels (upper neck-upper mediastinal gradient: 
      57% to - 21%). Therefore, significant ratios are meaningful only between either
      the symmetrical left and right controlateral quadrants, 8% of pre-operative
      scannings were non-contributory, and probe detection was contributory in 3/8
      cases only. Benefit of the technique is limited in routine, but it can be helpful
      in redo cases if the offending gland is not located in close surroundings of
      tissues physiologically taking up the radio pharmaceutical (salivary glands,
      great vessels and heart).

PMID- 12193874
TI  - [The endonasal approach to pituitary adenomas: experience in 105 procedures].
AB  - OBJECTIVE: The endonasal approach to the sella turcica is supposed to simplify
      surgical techniques and reduce the risk and sequelae linked to removal of
      pituitary adenomas. We report our experience with 105 procedures using this
      approach. METHOD: The series included 45 men and 60 women, aged 17 to 83 years.
      Their intrasellar lesions were: 43 non-functional adnomas, 37 prolactinomas, 7 GH
      adenomas, 9 corticotrop adenomas, 9 miscellaneous lesions (abscess, Rathke cleft
      cysts, empty sella). Mean duration of the procedures was 50 minutes. Mean
      hospital stay was 4 days. RESULTS: There were no deaths. Morbidity included: 1
      (0.95%) rhinorrhea associated with meningitis which cured without sequelae, 11
      (10.5%) transient diabetes insipidus lasting no longer than 48 hours, 2 cases of
      permanent diabetes insipidus (1 non-functional macroadenoma, 1 pituitary
      abscess), 1 transient hyposmia (3 months), 2 transient nasal obstructions. There
      were no cases of septal perforation, nasal deformation, partial or complete
      mucosal anesthesia, nasal pain, dental pain, or epistaxis. CONCLUSION: This
      surgical approach is easier to perform and causes less rhinological sequelae than
      the sublabial transsphenoidal approach. It allows an as effective tumor removal
      than the latter. Hospitalization stay is significantly shortened.

PMID- 12193875
TI  - [Iterative surgery for goiter].
AB  - AIM: Identify and resolve problems related to iterative surgery for goiter.
      PATIENTS AND METHOD: Fifty-nine patients who underwent surgery for recurrent
      benign goiter between 1990 and 1999 were included in the study. RESULTS: Forty
      two patients had lobectomy and isthmusectomy (71.2 and 17 patients had subtotal
      thyroidectomy (28.8%). The delay from initial surgery to recurrence was less than
      5 years for 44% of the patients and was more than 10 years for 17.8%. There was
      no post-operative mortality and no recurrent laryngeal nerve injury. Early post
      operative hypocalcemia occurred in 2 patients (3.3%). CONCLUSION: The goal of
      revision surgery for recurrent goiter is total thyroidectomy. Prevention is a
      rational management scheme for thyroid nodules.

PMID- 12193876
TI  - [Water homeostasis in the living: molecular organization, osmoregulatory reflexes
      and evolution].
AB  - Human body weight is about 70% water; 55% of the water are in cells and 45% in
      extracellular compartments, mainly body fluids. Each compartment has its own
      osmoregulatory system. The mechanisms of intracellular osmoregulation likely
      appeared with the cell itself, i.e. in primitive prokaryotes, some 3.8 billions
      years ago. Osmotic stress responses observed in present-day bacteria, yeast,
      plant and animals cells in culture are very similar. Variations in the cell
      volume entail an extension or retraction of plasma membrane that activates
      mechanically-gated ion channels or mechanoreceptors. Some of them have been
      cloned from E. coli, the nematode C. elegans, the drosophila. Osmotic stress
      determines an intracellular cascade of transactivations, the last transcription
      factor binding to a  Tonicity response element  (TonE) of osmoprotective genes.
      These genes encode enzymes synthesizing  compatible  osmolytes that reequilibrate
      the osmotic pressure. Volume and osmolality of the biological fluids (le milieu
      interieur) are regulated by neuroendocrine reflexes involving an afferent neural
      limb from baro- and osmo-receptors to hypothalamus and an efferent endocrine limb
      from neurosecretory cells to target cells, the hydroosmotic cells localized in
      osmoregulatory organs. Afferent signals trigger the biosynthesis and the
      processing of neurohypophyseal preprohormones in magnocellular neurons of the
      supraoptic and paraventricular nuclei of hypothalamus. Vasopressin in mammais and
      vasotocin in other vertebrates, endowed with antidiuretic and antinatriuretic
      properties, act on hydroosmotic cells localized in the nephron collecting duct. A
      specific vasopressin receptor, the V2 type receptor, located in the basolateral
      membrane of the principal cells, is coupled with an heterotridimeric protein Gs
      that activates adenylate cyclase. The cAMP product, in turn, stimulates the
      protein kinase A (PKA). The latter mobilizes 5 effectors located in the apical
      membrane: 1) the water channel aquaporin 2; 2) the urea transporter UT1; 3) the
      amiloride-sensitive sodium channel ENaC; 4) the inward-rectifying potassium
      channel ROM-K1; 5) the chloride channel CFTR. Modulation of each effector is
      ensured by an  A kinase anchoring protein  (AKAP). The effectors are transported
      from cytosol to apical membrane through transport vesicles equipped with membrane
      fusion proteins (such as VAMP2) that recognize specific apical membrane proteins
      (such as syntaxins). Water flows into principal cells from collecting duct lumen
      through AQP2 and flows out to interstitium through AQP3 and AQP4 and finally
      reachs blood circulation through AQP1 capillaries. Vasopressin orchestrates the
      live effectors so as to keep water and solutes reabsorptions in balance with
      volaemia and osmolality set points.

PMID- 12193877
TI  - Sarcoma of the thyroid gland: a case report.
AB  - Sarcoma of the thyroid gland is a very uncommon malignant tumor (<1% of thyroid
      cancers) characterized by severe local course and rapid metastatic dissemination
      and very poor prognosis. We report the case of an 84-year-old woman hospitalized
      for expiratory dyspnea, severe malnutrition and swallowing disorders leading to
      bronchial infection. She had a voluminous (20 cm) extra-thoracic right-neck
      goiter with a considerable superficial venous pattern that had developed on an
      old goiter before growing recently. CEA and calcitonin levels were normal. The
      cervical-thoracic CT demonstrated a partially necrosed heterogeneously hypodense
      tumor compressing the esophagus and the trachea with displacement of adjacent
      structures which were not directly invaded. Large areas of necrosis and a
      probable metastatic image measuring 3 cm in the right median pulmonary lobe were
      observed. Macrobiopsy disclosed grade 3 sarcoma. Complete resection delivered a
      3.170 kg tumor. Histology confirmed the diagnosis of sarcoma without neoplastic
      extension. Apart from right recurrent palsy, the initial post-operative period
      was satisfactory and the patient was discharged. Four and a half months later she
      was rehospitalized with local recurrence with a large metastatis in the right
      lung. She died two weeks later.

PMID- 12193878
TI  - [Post-partum autoimmune thyroiditis in a patient presenting with Sheehan's
      syndrome].
AB  - A 30-year-old women developed post-partum thyroiditis associated with post-
      partum pituitary infarction. Pituitary stimulation tests demonstrated global
      pituitary deficiency but there was no thyrotropin response to TRH stimulation and
      free T4 was normal. Associated goiter and high circulating levels of microsomal
      antibodies led to the diagnosis of post-partum thyroiditis associated with
      pituitary deficiency. Two cases of this unusual association have been reported.
      The underlying pathogenesis might involve post-partum immunological rebound
      and/or hypocorticism-induced immunological disorders.

PMID- 12193879
TI  - [Ectopic prolactinoma of the sphenoidal sinus: case report].
AB  - A 34-year-old woman was hospitalized for exploration of amenorrhea and
      galactorrhea. She had experienced primary sterility, diagnosed 11 years earlier.
      Endocrine tests demonstrated hyperprolactinemia (serum prolactin 594 ng/ml).
      Magnetic resonance imaging (MRI) showed a soft tissue mass located within the
      posterior part of the sphenoidal sinus. The pituitary gland appeared normal.
      Medical treatment with bromocriptine was unsuccessful. Transsphenoidal tumor
      resection was performed. Histology reported adenoma, which was consistent with
      prolactin-producing tumor demonstrated by immunohistochemical staining for
      prolactin. Because of the persistence of hyperprolactinemia related to an intra
      sphenoidal tumor remnant, bromocriptine (15 mg/d) was initiated. Menses ensued
      and prolactin level declined (49 ng/ml). One year later, the tumor remnant had
      disappeared on the MRI and the patient became pregnant. Ectopic adenomas of the
      sphenoidal sinus are of particular interest due to the diagnostic difficulties
      encountered. Nevertheless, the nature of the lesion can be determined from the
      endocrine manifestations. Some of these tumors respond to medical treatment,
      similar to intra sellar tumors. Surgery remains however the only means of
      obtaining definitive diagnosis and cure.

PMID- 12193880
TI  - [Primary lymphoma of the thyroid gland].
AB  - Malignant primary lymphoma of the thyroid gland is a rare disease generally
      occurring women in the 6(th) or 7(th) decade of life. The principal clinical sign
      is giant goiter rapidly leading to sings of compression, raising the question of
      differential diagnosis with anaplastic cancer. The radiological findings in our
      patient were suggestive of malignancy due to the locoregional invasion.
      Immunohistochemistry study of the surgical specimen was required to reach the
      definitive diagnosis of thyroid gland primary lymphoma. Diagnosis of malignant
      primary lymphoma of the thyroid gland made at the stage of extensive locoregional
      extension compromises prognosis. Our patient died after one session of
      chemotherapy.

PMID- 12193881
TI  - [Diabetic fibrous mastopathy: a case report].
AB  - Diabetic fibrous mastoplasty or diabetic fibrous breast disease is a benign
      condition rarely observed. First described in 1984, it can lead to misdiagnosis
      because it simulates breast cancer. Diabetic fibrous mastoplasty usually occurs
      in patients with autoimmune disorders, particularly in patients with longstanding
      and complicated insulin-dependent diabetes mellitus. We present a case of fibrous
      mastoplasty in a patient with insulin-dependent diabetes mellitus known for 17
      years. The clinical and radiological features and the clinical course are
      illustrative. We discuss the different pathogenic theories put forward.

PMID- 12193882
TI  - [Insulinoma with hyperproinsulinemia: a two cases report].
AB  - We report two cases of insulinoma with increased serum proinsulin levels and with
      normal insulin levels.Clinically, the two patients show typical symptoms of
      insulinoma, but serum insulin levels are normal. Only high levels of serum
      proinsulin allow us to retain the diagnosis of insulinoma. The new insulin assays
      using monoclonal antibodies are very specific for insulin and though can not
      detect isolated high proinsulin levels. So proinsulin assay is useful when
      diagnosing insulinoma.

PMID- 12193883
TI  - Effect of long-term dietary manipulation on the aggregation of rat lens
      crystallins: role of alpha-crystallin chaperone function.
AB  - PURPOSE: To investigate the effect of food, protein, and vitamin restriction on
      the susceptibility of lens crystallins to aggregation and chaperone activity of
      alpha-crystallin. METHODS: Thirty day old Wistar/NIN rats were maintained on
      regular rodent diet (C), 50% food restriction (FR), 75% protein restriction (PR),
      and 50% vitamin restriction (VR) diet for 20 weeks. At the end, alpha-, beta-,
      and gamma-crystallins were isolated from the lenses of these animals and
      subjected to in vitro aggregation induced by oxidation, UV irradiation and heat.
      Aggregation and chaperone activity was assessed by light scattering methods.
      RESULTS: Dietary restriction has been shown to extend the mean and maximum life
      span and retard age-related diseases, including cataract. In this study, we
      demonstrate that while beta- and gamma-crystallins isolated from FR and PR groups
      were less susceptible to in vitro induced aggregation, beta- and gamma
      crystallins from the VR group were more susceptible, compared to controls. Alpha
      crystallin from any of the groups did not shown a considerable amount of
      aggregation. On the other hand, the chaperone activity of alpha-crystallin from
      FR and PR groups was not significantly different from controls. However, alpha
      crystallin from the VR group demonstrated substantially higher chaperone activity
      than controls. CONCLUSIONS: These results indicate that while food and protein
      restriction appear to lower the susceptibility of beta- and gamma-crystallins
      towards aggregation, vitamin restriction tends to increase the aggregation.
      Chaperone activity of alpha-crystallin is affected (improved) by only vitamin
      restriction.

PMID- 12193885
TI  - Evidence-based dentistry.

PMID- 12193886
TI  - The use of bioabsorbable osteofixation devices in craniomaxillofacial surgery.
AB  - Because of problems associated with the conventional osteofixation devices used
      in craniomaxillofacial surgery, bioabsorbable devices have presented an appealing
      alternative. Devices made of the polymers polyglycolide (PGA) and polylactide
      (PLA) and their copolymers (PLGA and PLDLA) are currently the most commonly used.
      Strong implants can be manufactured from these polymers with a self-reinforcing
      technique and used in the treatment of fractures and osteotomies. Self-reinforced
      devices have been studied for nearly 2 decades by our multidisciplinary research
      group for internal fixation of the bone in both experimental and clinical
      settings. In craniomaxillofacial fractures and osteotomies they have been used
      for as long as 10 years with no significant clinical problems. Because of more
      favored degradation characteristics, currently the copolymer devices (PLDLA and
      PLGA) represent the advancing front in the application of absorbable devices in
      craniomaxillofacial surgery. By using bioabsorbable devices, several problems
      associated with conventional biostable devices can be avoided, especially in
      children. New techniques that are not possible with biostable devices can be
      developed by using bioabsorbable devices, too. Our experience with and research
      on self-reinforced devices are shared here.

PMID- 12193887
TI  - Delayed signs and symptoms after oropharyngeal trauma in a child.
AB  - Injury to the oropharynx can be potentially life threatening. Innocent-looking
      injuries of the oropharynx may result in intravascular thrombosis of the internal
      carotid artery. The symptoms often appear some time after the initial injury. We
      present a case in which an apparently minor injury of the oropharynx developed
      into a life-threatening thrombus stretching from the internal carotid to the
      brain. Our patient underwent endarterectomy and thrombectomy. The case is
      presented with a review of the literature.

PMID- 12193888
TI  - Stability of the Le Fort I osteotomy for maxillary advancement using rigid
      fixation and porous block hydroxyapatite grafting.
AB  - PURPOSE: The purpose of this study was to evaluate the stability of maxillary
      advancement using bone plates for skeletal stabilization and porous block
      hydroxyapatite (PBHA) as a bone graft substitute for interpositional grafting.
      PATIENTS AND METHODS: The records of 78 patients (55 female, 23 male) with a
      diagnosis of anteroposterior maxillary hypoplasia were retrospectively evaluated.
      All patients underwent greater than 5 mm Le Fort I maxillary advancement with
      rigid fixation and PBHA interpositional grafting. The study sample was divided
      into 3 groups on the basis of the concurrent superior or inferior positioning of
      the maxillary incisors. Presurgery (T1), immediately postsurgery (T2), and
      longest follow-up (T3) lateral cephalometric tracings were superimposed to
      analyze for horizontal and vertical changes at the following landmarks: (1) point
      A, (2) incisal edge of the maxillary incisor, and (3) mesial cusp tip of
      maxillary first molar. RESULTS: The maxilla was inferiorly repositioned in 27
      patients, superiorly repositioned in 21 patients, and advanced horizontally
      without a significant vertical change in 30 patients. All groups showed 0.5 mm or
      less horizontal and vertical relapse. There was no statistically significant
      difference between the 3 groups. CONCLUSIONS: Maxillary advancement with Le Fort
      1 osteotomies by using rigid fixation and interpositional PBHA grafting is a
      stable and predictable procedure regardless of the direction of vertical
      maxillary movement.

PMID- 12193889
TI  - The temporalis muscle flap in reconstruction of intraoral defects: an appraisal
      of the technique.
AB  - PURPOSE: The purpose of this article is to review the experience of the authors
      in the use of the temporalis muscle flap for reconstruction of intraoral defects.
      PATIENTS AND METHODS: This is a retrospective review of the use of the temporalis
      muscle flap for reconstruction of different types of intraoral defects in 8
      patients. All patients in this series previously wore obturators as a nonsurgical
      treatment of their defects. Criteria used to evaluate the results of this
      technique included flap necrosis, facial nerve deficit, limitation of mandibular
      range of motion, and cosmetic deformity from scarring of the incision line or
      from loss of muscle volume in the temporal fossa. The patients were also
      evaluated for their degree of satisfaction with their speech and mastication with
      the obturator preoperatively and with the flap postoperatively. This article also
      reviews the success rates and complications with use of the temporalis muscle
      flap reported in the English-language literature during the past 14 years.
      RESULTS: All 8 patients in this series had their defects successfully
      reconstructed, completely eliminating any further need for prosthetic obturation
      of the defect. There were no incidents of flap necrosis, facial nerve deficit, or
      long-term changes in mandibular range of motion. Slight temporal hollowing was
      seen in the first 3 patients. Results of the literature review also showed a high
      success rate and a low incidence of complications with use of this flap.
      CONCLUSIONS: The temporalis flap is a useful, reliable, and versatile option for
      reconstruction of moderate to large sized defects. The muscle can provide
      abundant tissue, with minimal to no functional morbidity or esthetic deformity in
      the donor site.

PMID- 12193890
TI  - Synovial chondromatosis of the temporomandibular joint: clinical, diagnostic, and
      histomorphologic findings.
AB  - Objective. The primary diagnosis of synovial chondromatosis of the
      temporomandibular joint is extremely rare. Often many months, or even years pass
      before the diagnosis is confirmed. Study Design. Eight patients with synovial
      chondromatosis were treated by arthrotomy. In addition to the definitive
      diagnosis, histologic classification according to the stages proposed by Milgram
      was undertaken and confirmed with the literature. Results. The predominant
      symptoms of synovial chondromatosis, including pain, swelling, restricted
      movement of the mandible, and crepitation, were evaluated. Nevertheless, more
      than 80% of the patients were previously primarily treated on the basis of other
      tentative diagnoses. Conclusion. Synovial chondromatosis of the temporomandibular
      joint should be included in the differential diagnosis of chronic swelling and
      pain in the preauricular region, and the patient should be sent for appropriate
      diagnostics and therapy at an early stage.

PMID- 12193891
TI  - The role of salivary function in modulating chemotherapy-induced oropharyngeal
      mucositis: a review of the literature.
AB  - Oropharyngeal mucositis is a common and significant complication of cancer
      chemotherapy and limits the delivery of chemotherapy, affects the quality of
      life, and increases the cost of care. Oral mucositis caused by cancer
      chemotherapy is associated with specific agents, but the origin of oral mucositis
      is poorly understood. These drugs may have direct toxic effects on the rapidly
      dividing cells of the oral mucosa and on cellular elements of the connective
      tissue. Microbial flora may play a role in the development of ulcerative
      mucositis. Chemotherapy may be directly toxic and affect the mucosa by systemic
      circulation and may be related to secretion of some chemotherapeutic drugs in the
      saliva, resulting in topical exposure to the oral environment. Other potential
      mechanisms include reduced saliva volume and change in saliva constituents that
      may affect epithelial maintenance and repair, the physiology of the oral
      microflora, and the interaction between the oral flora and the epithelium.
      Improved understanding of the mechanisms whereby specific chemotherapeutic agents
      cause mucositis may lead to management approaches that will reduce the incidence
      and severity of mucositis, improving quality of life and ensuring delivery of the
      necessary chemotherapy to improve cancer cure rates.

PMID- 12193892
TI  - Large myelinated nerve fiber hypersensitivity in oral malignancy.
AB  - OBJECTIVES: The purpose of this study was to assess the sensory function of
      trigeminal nerve A-beta fibers in suspected soft tissue oral malignancies. STUDY
      DESIGN: Twenty-three patients referred for the evaluation of an oral lesion
      suspected of malignancy were included in the study. All lesions were classified
      as in, near, or out of the nerve territory containing the lesion. Within these
      subgroups we assessed the sensitivity of A-beta primary afferents to weak
      electrical currents applied bilaterally to regions innervated by 3 peripheral
      branches of the trigeminal nerve. The ratio of electrical detection thresholds
      from the affected and the unaffected side was calculated. Electrical detection
      threshold ratios were contrasted with the results of physical examination,
      radiographic imaging, and biopsy. RESULTS: For dermatomes containing the lesions,
      ratios were lower than 0.8 in 12 patients. Biopsy showed that the lesions in 10
      of these 12 patients were malignant. No malignancy was found in the remaining 11
      patients. CONCLUSIONS: A-beta primary afferent hypersensitivity is observed to
      occur in nerves exposed to soft tissue oral malignancy.

PMID- 12193893
TI  - Hereditary pattern for dentinal dysplasia type Id: a case report.
AB  - Generalized pulpal calcifications arouse suspicion of diseases or conditions of
      systemic or hereditary origin. This case report describes a 45-year-old patient
      with generalized pulpal calcifications and bulging of the roots in areas
      corresponding to the pulp chambers in otherwise normal teeth. Similar findings
      were present in the patient's daughters and brother. This pattern of pulpal
      calcifications is consistent with the hereditary condition of dentinal dysplasia
      type Id.

PMID- 12193894
TI  - Multiple intraoral melanoacanthomas: a case report with unusual findings.
AB  - Melanoacanthoma is a rare, benign, mucocutaneous pigmented lesion characterized
      by colonization of acanthotic epithelium by dendritic melanocytes.(1,2) The most
      common intraoral sites are the buccal(3,4) and masticatory mucosa subject to
      chronic irritation.(1,5) The pathogenesis of oral melanoacanthoma remains
      uncertain, although its clinical behavior is suggestive of a reactive
      cause.(3,4,6,7) The clinical appearance of melanoacanthoma is nondiagnostic, and
      biopsy is mandatory.(2,3,5,6,8) The lesion, however, requires no treatment(5) and
      elimination of local irritants as well as periodic observation are the
      recommended interventions.(1,8) We describe a 39-year-old black patient with a
      recently reported palatal melanoacanthoma who developed additional lesions in
      other intraoral sites approximately 3 months after the initial lesion was
      biopsied. This article also documents the reactive and reversible nature of
      intraoral melanoacanthoma in a rare case of multiple lesions.

PMID- 12193895
TI  - Oral surgery in patients on anticoagulant therapy.
AB  - OBJECTIVE: Surgery is the main oral healthcare hazard to the patient with a
      bleeding tendency, which is mostly caused by the use of anticoagulants. The
      traditional management entails the interruption of anticoagulant therapy for
      dental surgery to prevent hemorrhage. However, this practice may increase the
      risk of a potentially life-threatening thromboembolism. Because this issue is
      still controversial, it is the aim of this paper to review the evidence, to
      highlight the areas of major concern, and to suggest management regimens for
      patients on the 3 main types of anticoagulants: coumarins, heparins, and aspirin.
      MATERIALS REVIEWED: The pertinent literature and clinical protocols of hospital
      dentistry departments have been extensively reviewed and discussed. RESULTS:
      Several evolving clinical practices in the last years have been detected:
      anticoagulant use is generally not discontinued; oral surgery is performed
      despite laboratory values showing significant bleeding tendency; new effective
      local methods are used to prevent bleeding; and patients at risk are referred to
      hospital-based clinics. CONCLUSION: The management of oral surgery procedures on
      patients treated with anticoagulants should be influenced by several factors:
      extent and urgency of surgery, laboratory values, treating physician's
      recommendation, available facilities, dentist expertise, and patient's oral,
      medical, and general condition.

PMID- 12193896
TI  - Silicone granuloma of the facial tissues: a report of seven cases.
AB  - The liquid form of silicone, called dimethicone (dimethylpolysiloxane), has been
      used extensively in some countries during the past 4 decades for soft tissue
      augmentation. Although considered biologically inert, this material has been
      reported as potentially inducing, after tissue injection, a granulomatous
      inflammatory response of variable severity. Interestingly, a remarkable paucity
      of reports exists about the development of complications after injections of
      liquid silicone into the facial tissues, especially considering its high
      frequency of use. The purpose of this article is to describe the clinical and
      microscopic features of 7 cases of silicone-induced granulomas that developed
      after injection of the facial tissues for cosmetic purposes and to discuss the
      differential diagnosis and management of this condition.

PMID- 12193897
TI  - Central odontogenic fibroma-like tumors, hypodontia, and enamel dysplasia: review
      of the literature and report of a case.
AB  - A patient with multiple odontogenic fibroma-like tumors in the mandible and
      enamel dysplasia is presented, bringing the total number of cases reported in the
      literature to 3. In addition to these manifestations, this case had hypodontia.
      The absence of associated teeth, the size of the lesions, the lingual expansion,
      and the green-yellow polarization of collagen with Picrosirius stains supported
      the neoplastic nature of the central odontogenic fibroma-like tumors in the case
      presented. Laminated psammomatous deposits distinguished the tumors from the
      World Health Organization-type central odontogenic fibroma.

PMID- 12193898
TI  - Solitary fibrous tumor of the parotid gland: a case report.
AB  - The solitary fibrous tumor is traditionally associated with a mesothelial-lined
      surface. However, any organ with mesenchymal tissue has the potential for
      developing this tumor; therefore, it has been described in organs not associated
      with serosal surfaces. We report a case of solitary fibrous tumor of the parotid
      gland. Microscopically, the tumor showed a patternless arrangement of spindle
      cells in a fibrotic background and prominent vascular structures of varying size.
      Tumor cells showed a strong immunoreactivity for CD34 and bcl-2 antigens, but the
      tissue was negative for antibodies directed against actins, S-100 protein, and
      cytokeratins. One year after excision, the patient was alive and without evidence
      of disease.

PMID- 12193899
TI  - Actinic prurigo cheilitis: clinicopathologic analysis and therapeutic results in
      116 cases.
AB  - Objective. This study describes the clinicopathologic features and therapeutic
      results of 116 patients with actinic prurigo cheilitis seen over an 11-year
      period. Study Design. A retrospective study was carried out with hospital records
      and a microscopic slide review from a large dermatology department in Mexico
      City, Mexico. Results. The study consisted of 42 male (36.2%) and 74 female
      (63.8%) patients, with a male to female ratio of 1:1.7. Age ranged from 9 to 82
      years (mean, 27.9 years; standard deviation, 14.2). Thirty-two cases (27.6%) were
      found in which cheilitis was the only manifestation of this condition. Pruritus,
      tingling, and pain of the vermilion were recorded in 96 cases (82.7%). Typical
      histopathologic findings included in most cases the presence of acanthosis,
      spongiosis, basal cell vacuolation, ulceration with serohematic crust formation,
      edema of the lamina propria, lymphocytic inflammatory infiltrate with well
      defined lymphoid follicles, and variable numbers of eosinophils and melanophages.
      Improvement of the symptoms was obtained in 112 cases (96.5%) with sun-protective
      measures and diverse antiinflammatory agents. However, complete resolution of the
      labial lesions were more frequently achieved with the combination of topical
      steroids, thalidomide, and sun-protective measures (42.2%) as compared with
      topical steroid therapy plus sun-protection measures (16.3%; P <.005).
      Conclusion. Our findings confirm that lip lesions may appear as the only
      manifestations of this photodermatosis and that it has typical clinical and
      microscopic features and should therefore be considered a specific form of
      cheilitis.

PMID- 12193901
TI  - Intracanal placement of calcium hydroxide: a comparison of two different mixtures
      and carriers.
AB  - Objective. The purpose of this study was to compare the placement techniques of
      Ca(OH)(2). Study Design. Forty simulated curved canals (42 degrees) in
      transparent resin blocks were used and separated into 4 experimental groups, 10
      canals each. A paste of Ca(OH)(2) was mixed with either water or glycerin and
      placed into canals with Lentulo spiral or Pastinject. Radiographs were taken of
      each sample. The canal fillings were evaluated by 3 endodontists and scored as to
      length of placement and completeness of fill. Cohen's kappa test was used to
      measure agreement between raters, and Kruskal-Wallis analysis of variance test
      was used to determine statistical differences between the 4 groups. Results. As
      to length of placement, statistically significant differences were found between
      Ca(OH)(2) + water pastes filled with Lentulo spiral (group 1) and Ca(OH)(2) +
      glycerin pastes filled with either Pastinject or Lentulo spiral. The findings of
      group 1 showed that the paste was short of the apex by more than 2 mm, whereas
      the other 3 groups were either at the apex or only 1 to 2 mm short. As to middle
      and coronal completeness of fill, differences were found to be statistically
      significant between Ca(OH)(2) + water paste filled with Lentulo spiral group and
      the other groups. Most of the canals in group 1 had greater than one-half void
      space at apical third, whereas the canals had less than one-fourth void space
      when Ca(OH)(2) + glycerin pastes were filled with Pastinject. Conclusions.
      Ca(OH)(2) when mixed with glycerin and placed into the canals, either with a
      Lentulo spiral or Pastinject, provided satisfactory results. Pastinject showed
      better fillings with Ca(OH)(2) + water pastes than Lentulo spiral.

PMID- 12193902
TI  - Calcium hydroxide as a temporary filling of the post space in root-filled teeth.
AB  - OBJECTIVE: The purpose of this in vitro study was to evaluate whether the saline
      content of the calcium hydroxide paste used as a temporary filling in the post
      space of root-filled teeth would significantly affect the seal of the apical root
      fillings (gutta-percha and zinc oxide-eugenol based sealer) during a period of 1
      month. STUDY DESIGN: Eighty extracted single-rooted and multirooted teeth were
      cut at the cemento-enamel junction. They were endodontically instrumented and
      filled with zinc oxide-eugenol based sealer and gutta-percha. A post space was
      immediately prepared on 70 teeth. The experimental teeth were then randomly
      divided into 4 groups: A, post space filled with calcium hydroxide paste (30
      teeth); B, post space without calcium hydroxide paste (30 teeth); C, negative
      controls (10 teeth); and D, positive controls (10 teeth). The teeth were stored
      in a humidified chamber at room temperature for a month. After storage, the
      calcium hydroxide paste in the post spaces in group A was removed. All roots were
      coated with 2 layers of nail varnish and sticky wax externally, placed in a glass
      bottle containing methylene blue, and subjected to a vacuum for 15 minutes. The
      teeth were then stored for another week, sectioned in half longitudinally, and
      examined for dye penetration. The mean and standard deviation of dye penetrations
      for each group were calculated, and a Student t test was used to determine the
      statistical difference between the groups. RESULTS: There was no significant
      difference in the coronal dye leakage of the apical root fillings between the
      post spaces filled with the calcium hydroxide paste and those without during a
      period of 1 month. CONCLUSIONS: The saline content in the calcium hydroxide paste
      placed in the post space as a temporary filling did not significantly affect the
      seal of the apical root fillings during a period of 1 month by using a dye
      leakage study.

PMID- 12193903
TI  - Age-related changes in the immunoreactivity of the monocyte/macrophage system in
      rat molar pulp after cavity preparation.
AB  - OBJECTIVE: Our objective was to compare the response of the monocyte/macrophage
      system of dental pulp to cavity preparation in aged rats (12 and 18 months old)
      with that seen in young adult rats (3 and 6 months old). STUDY DESIGN: Cavities
      were prepared on the upper first molars, and the lower first molars served as
      intact controls. Specimens were collected at 1 day after cavity preparation, and
      cryostat sections were made. RESULTS: Accumulation of OX6+ antigen-presenting
      cells along the pulp-dentin border and a marked increase in cell size ED2+
      resident macrophages were noted in both young adult and aged rats after cavity
      preparation. In both cases, the number of ED1+ cells increased significantly
      after cavity preparation because of infiltrating monocytes. CONCLUSION: These
      findings suggest that the pulpal defense reaction of the monocyte/macrophage
      system to cavity preparation in aged rats does not differ markedly from that in
      young adult rats.

PMID- 12193904
TI  - Proliferative periostitis of Garre: Report of a case.
AB  - Proliferative periostitis of Garre is described as a productive and proliferative
      inflammatory response of periosteum to infection or other irritation. This can be
      odontogenic or non-odontogenic in nature. This is a case report of an odontogenic
      periostitis resulting from periapical inflammation of endodontic origin. It was
      successfully treated by nonsurgical endodontics. Antibiotic therapy was not used
      during the treatment of this patient.

PMID- 12193905
TI  - Comparison of ultrasonography with magnetic resonance imaging in the diagnosis of
      temporomandibular joint internal derangements: a preliminary investigation.
AB  - OBJECTIVE: This study aimed to compare ultrasonography (US) with magnetic
      resonance imaging (MRI) with respect to the diagnosis of temporomandibular joint
      (TMJ) internal derangements. STUDY DESIGN: The study group consisted of 23
      patients with a chief complaint of TMJ discomfort who were tentatively diagnosed
      by means of head-neck examination as having TMJ internal derangements and a
      control group of 9 volunteers who had no sign of TMJ internal derangements. All
      the patients were then examined by means of MRI and US. RESULTS: The results
      showed perfect agreement between MRI and US in the diagnosis of TMJ internal
      derangements (kappa = 1.000; P =.0001). CONCLUSION: MRI and US can be used to
      define the disk and its position, as well as the presence of TMJ internal
      derangements.

PMID- 12193906
TI  - The application of a radiotherapy-planning system: consideration from a case of
      intraoral squamous cell carcinoma that lacked a control.
AB  - OBJECTIVE: The purpose of this case study was to present an applied example of a
      radiotherapy-planning system used during the treatment of a malignant tumor in
      the oral and maxillofacial region. STUDY DESIGN: The various radiotherapy
      modalities were performed on a patient with oral squamous cell carcinoma of
      multiple metachronous recurrences. Estimated radiation dose-distribution curves
      for each radiotherapy modality were computed by using a commercially available
      radiotherapy-planning system. A personal computer was used to make the
      superimposed radiation dose-distribution curve. RESULTS: The 3-dimensional dose
      distribution curves were determined with the radiotherapy-planning system. In
      addition, with the use of superimposition of the dose-distribution curves from
      all sources of radiotherapy, it was possible to estimate regions receiving
      extremely high radiation dosages. This information serves as a road map to
      potential postradiation complication sites at follow-up examinations. CONCLUSION:
      The radiotherapy-planning system is very useful for the evaluation of a
      radiotherapy dosage to treat malignant tumors in the oral and maxillofacial
      region.

PMID- 12193909
TI  - Physician heal thyself.

PMID- 12193907
TI  - Parotid sialography for diagnosing Sjogren syndrome.
AB  - OBJECTIVE: Despite the availability of many new imaging procedures, sialography
      has, after decades of use, maintained its status as the imaging procedure of
      choice for evaluating the oral component of Sjogren syndrome (SS). In this study,
      the clinical value of sialography as a diagnostic tool in SS was explored by
      assessing its diagnostic accuracy, observer bias, and staging potential. METHODS:
      One hundred parotid sialograms were interpreted independently in a blinded
      fashion by 2 trained and 2 expert observers. Sialograms were derived from a group
      of consecutive patients referred for diagnostics of SS. Patients were categorized
      as SS and non-SS by the revised European classification criteria. RESULTS:
      Trained observers reached a sensitivity of 95 and a specificity of 33% for SS by
      sialogram, whereas expert observers reached a sensitivity of 87 and a specificity
      of 84%. There was only "fair" interobserver agreement between trained and expert
      observers, whereas both expert observers showed "good" agreement with one
      another, according to Cohen's kappa. Intraobserver agreement was "good" to "very
      good" for all observers. The 4 different gradations of sialectasia, ie, punctate,
      globular, cavitary, and destructive, showed a weak but significant correlation
      with the duration of oral symptoms. CONCLUSIONS: This study markedly shows that
      the diagnostic value of parotid sialography for diagnosing SS greatly depends on
      the skills of the observer, implying that sialography lacks general applicability
      as a diagnostic tool in SS and requires specific expertise. Nevertheless, given
      its potentially high sensitivity and specificity in diagnosing SS as well as its
      useful staging potential, sialography still has its use in the evaluation of the
      oral component of SS.

PMID- 12193910
TI  - Preterm premature rupture of the membranes is associated with a reduction in
      neonatal respiratory distress syndrome.
AB  - OBJECTIVE: The purpose of this study was to evaluate the effect of preterm
      premature rupture of the membranes on the frequency of respiratory distress
      syndrome among singleton pregnancies that are complicated with preterm delivery.
      STUDY DESIGN: We performed a retrospective analysis of singleton pregnancies that
      were delivered between 24 and 34 weeks of gestation. Patients were categorized on
      the basis of membrane integrity into two groups: ruptured versus intact. All
      patients received prophylactic antibiotics and a single course of antenatal
      betamethasone. Data were analyzed with the Student t test, the chi(2) test, and
      the Fisher exact test. Multiple logistic regression analysis was performed to
      examine the effect of possible confounding variables that were considered risk
      factors for respiratory distress syndrome. Probability values of <.05 for all two
      tailed tests were considered significant. RESULTS: A total of 366 patients were
      included (99 patients in the preterm premature rupture of the membranes group and
      267 patients in the intact membranes group). Patients were delivered at 30.7 +/-
      2.9 and 30.1 +/- 2.7 (mean +/- SD) weeks of gestation, with birth weights of 1620
      +/- 594 and 1417 +/- 501 g, respectively. The frequency of respiratory distress
      syndrome in the neonate was significantly lower in the preterm premature rupture
      of the membranes group than in their intact counterparts (17% vs 39%, P <.001).
      Multiple logistic regression analysis confirmed that preterm premature rupture of
      the membranes (odds ratio, 0.16; 95% CI, 0.08-0.34) was independently associated
      with a reduction in the frequency of respiratory distress syndrome. CONCLUSION:
      In the clinical setting of delivery before 34 weeks of gestation, preterm
      premature rupture of the membranes is associated with a significant decrease in
      the frequency of neonatal respiratory distress syndrome.

PMID- 12193911
TI  - Misoprostol versus low-dose oxytocin for cervical ripening: a prospective,
      randomized, double-masked trial.
AB  - OBJECTIVE: A variety of cervical ripening agents exist, yet none is ideal. We
      performed a prospective, randomized, double-masked comparison of low-dose minimal
      escalation oxytocin to misoprostol in a predominantly high-risk population. STUDY
      DESIGN: Patients were allocated prospectively in a double-masked, randomized,
      stratified basis by an investigational pharmacist between December 1996 and
      December 2000 to receive either active intravenous oxytocin and placebo
      intravaginal misoprostol or intravenous placebo oxytocin and 50 microg of active
      intravaginal misoprostol. The infusion rate of oxytocin was increased from 1 to 4
      mU/min; misoprostol (25 microg) was repeated at 4 hourly intervals if there were
      <3 uterine contractions per 10-minute interval. RESULTS: Demographic
      characteristics did not differ between study groups nor did the indications for
      induction. Overall, the interval to delivery was less in the misoprostol group;
      however, vaginal delivery occurred in 61% versus 66% (not significant) of
      patients in the misoprostol versus oxytocin group. Indication for cesarean
      delivery in the misoprostol group was fetal intolerance to labor in 27% compared
      with 8% in the oxytocin groups (P <.05), whereas labor abnormalities were more
      commonly the cause in the oxytocin group versus misoprostol (26% vs 10%, P <.05).
      The proportion of patients was similar in each group overall and when evaluated
      on the basis of parity and when delivery was compared at 12, 24, and 36 hours
      after the initiation of cervical priming. CONCLUSION: Our data indicate that
      misoprostol and low-dose minimal-escalation oxytocin appear to be equally
      effective for cervical priming. Low-dose oxytocin may have a preferential role in
      the high-risk parturient whose fetus is at increased risk for fetal intolerance
      to labor

PMID- 12193912
TI  - Paget's disease of the vulva.
AB  - OBJECTIVE: Our goal was to review our experience with Paget's disease of the
      vulva relative to initial examination, treatment, and oncologic outcome. STUDY
      DESIGN: Patients who were treated for extramammary Paget's disease of the vulva
      at the University of South Florida were identified in our vulvar cancer database
      for the period 1988 through 2000. The charts were reviewed, and the data were
      collected regarding patient demographics, previous Paget's treatment, symptoms,
      surgical margin status, associated malignancies, and time to recurrence. RESULTS:
      Twenty-three women with extramammary Paget's disease of the vulva were treated by
      the Division of Gynecologic Oncology during the 12-year period. The average
      patient was postmenopausal and white and had symptoms for 21 months before the
      diagnosis was made. A pruritic lesion was the most common symptom. Treatment
      included wide local excision or vulvectomy, depending on the extent of disease.
      Six of the 23 patients displayed invasive disease and, consequently, underwent
      radical resection. There were 8 recurrences that were found, on average, 30
      months after the surgical procedure. Two of the 8 patients had invasive disease
      at their primary operation, and 1 patient had underlying invasive disease at the
      time of recurrence. The average follow-up time was 39 months (median, 13.5
      months; range, 1-216 months). CONCLUSION: Delay in diagnosis did not correlate
      with size or extent of disease. Margin status did not change the natural course
      of disease. Recurrence is relatively common, and long-term monitoring is
      recommended, with repeat excision of symptomatic lesions.

PMID- 12193913
TI  - Age and resting follicle number predict response to gonadotropin stimulation in
      in vitro fertilization cycles.
AB  - OBJECTIVE: The purpose of this study was to assess whether age, resting follicle
      number, intraovarian blood flow, and/or ovarian volume are predictive of
      follicular response and oocyte quality in patients with in vitro fertilization.
      STUDY DESIGN: A retrospective chart review was done on 90 in vitro fertilization
      cycles that were completed in a university setting. Multiple linear regression
      analysis was used to assess the predictive value of age, resting follicle number,
      pretreatment ovarian volume, and peak systolic velocity for response to
      gonadotropin stimulation. RESULTS: Age was predictive (P <.05) for the number of
      oocytes retrieved, the number that reached two pronuclei, and the number of
      embryos that reached > or = 4 cells by day 3 after insemination. Resting follicle
      number was also predictive of follicular response and subsequent embryonic
      development. Peak systolic velocity and ovarian volume were both found to be of
      no value. CONCLUSION: Age and resting follicle number can be used as additional
      parameters to support patient counseling before in vitro fertilization
      stimulation.

PMID- 12193914
TI  - Estrogen replacement therapy in patients with early breast cancer.
AB  - OBJECTIVE: Most physicians believe that estrogen replacement therapy is
      contraindicated once a patient is diagnosed with breast cancer. Recently, several
      studies have shown that estrogen replacement therapy may be safely used in
      patients with early breast cancer that has been treated successfully. These women
      can have severe menopausal symptoms and are at risk for osteoporosis. We reviewed
      the current status of women in our practice with breast cancer who received
      estrogen replacement therapy, who did not receive hormone replacement therapy,
      and who did not receive estrogenic hormone replacement therapy. STUDY DESIGN: The
      study group consisted of 123 women (mean age, 65.4 +/- 8.85 years) who were
      diagnosed with breast cancer in our practice, including 69 patients who received
      estrogen replacement therapy for < or = 32 years after diagnosis. The comparative
      groups were 22 women who used nonestrogenic hormones for < or = 18 years and 32
      women who used no hormones for < or = 12 years. The group who did not receive
      estrogenic hormone replacement therapy received androgens with or without
      progestogens (such as megestrol acetate). Of the 63 living hormone users, 56
      women are still being treated in our clinic, as are 15 of the 22 subjects who
      receive nonestrogenic hormone replacement therapy. Follow-up was done through the
      tumor registry at University Hospital; those patients whose tumor records were
      not current were contacted by telephone. RESULTS: There were 18 deaths in the 123
      patients: 6 patients who received estrogen replacement therapy (8.69%), 2
      patients who received nonestrogenic hormone replacement therapy (9.09%), and 10
      patients who received no hormone replacement therapy (31.25%). Of the 18 deaths,
      9 deaths were from breast cancer (mortality rate, 7.3%); 3 deaths were from lung
      cancer; 1 death was from endometrial cancer; 1 death was from myocardial
      infarction; 1 death was from renal failure; and 3 deaths were from
      cerebrovascular accidents. The 9 deaths from breast cancer included one patient
      who received nonestrogenic hormone replacement therapy (mortality rate, 4.5%), 6
      patients who received no hormone replacement therapy (mortality rate, 11.3%), and
      2 patients who received estrogen replacement therapy (mortality rate, 4.28%). The
      9 non-breast cancer deaths included 4 patients who received estrogen replacement
      therapy (endometrial cancer [1 death], lung cancer [1 death], cerebrovascular
      accident [1 death], and renal failure [1 death]), 1 patient who did not receive
      estrogenic hormone replacement therapy group (myocardial infarction), and 4
      patients who used no hormones (lung cancer, 2 deaths; stroke, 2 deaths).
      Carcinoma developed in one patient in the estrogen replacement therapy group in
      the contralateral breast after 4 years of hormone replacement therapy; she is
      living and well 2.5 years later with no evidence of disease. Metastatic breast
      cancer developed in one patient after 8 years of hormone replacement therapy; she
      is living with disease. CONCLUSION: Estrogen replacement therapy apparently does
      not increase either the risk of recurrence or of death in patients with early
      breast cancer. These patients may be offered estrogen replacement therapy after a
      full explanation of the benefits, risks, and controversies.

PMID- 12193915
TI  - End-of-life discussions for the primary care obstetrician/gynecologist.
AB  - This review of end-of-life decisions centers on the role of the
      obstetrician/gynecologist in assisting women patients to develop advanced
      directives that are targeted to unique risks of the pregnant woman; these risks
      are related to trauma, cancer, and aging; to the special need for lesbian couples
      to identify health proxies; and to the woman's responsibilities as a caregiver to
      ensure advance directives and medical proxies for the family. End-of-life
      decisions are much more stressful when surrogate decision makers do not know in
      advance what decisions a patient would want made if the patient becomes
      incapacitated.

PMID- 12193916
TI  - Ectopic pregnancy within a cesarean delivery scar: a case report.
AB  - The implantation of a pregnancy within the scar of a previous cesarean delivery
      is the rarest of ectopic pregnancy locations. If it is diagnosed early, treatment
      options are capable of preserving the uterus and subsequent fertility. However, a
      delay in either diagnosis or treatment can lead to uterine rupture, hysterectomy,
      and significant maternal morbidity.

PMID- 12193917
TI  - Necrotizing fasciitis in gynecologic and obstetric patients: a surgical
      emergency.
AB  - OBJECTIVE: We reviewed the cases of 23 patients who were admitted to the hospital
      with a primary diagnosis of histopathologically confirmed necrotizing fasciitis
      in the lower abdomen or pelvis. Rapid demise of a healthy postpartum women piqued
      our interest in trying to identify the early signs and symptoms that may lead to
      earlier diagnosis and treatment of this often fatal disease. STUDY DESIGN: A
      retrospective analysis of charts of all patients who were admitted to the
      gynecology and obstetrics services of our hospital systems with a diagnosis of
      necrotizing fasciitis for the past 14 years was performed. Age, comorbid factors,
      precipitating events, weight, symptoms and signs, microbiologic factors,
      radiographs, surgical therapy, and morbidity were correlated. RESULTS: Definitive
      operation was accomplished within 48 hours of the diagnosis of necrotizing
      fasciitis in all but 3 patients. Of the 17 patients who were not puerperal, 88%
      of the women were obese; 65% of the women were hypertensive, and 47% of the women
      were diabetic. Of the total 23 patients, 70% of the women complained of severe
      pain, and 35% of the women had radiographic diagnostics for necrotizing fasciitis
      ("gas"). Four patients had diverting colostomies, and 39% of the patients had
      flaps or synthetic grafts. Three patients died (mortality rate, 13%). One patient
      who was puerperal died of a severe rapid septicemia; the 2 late deaths were the
      result of systemic candidiasis. CONCLUSION: Necrotizing fasciitis is a rapidly
      progressive, often lethal, infectious disease process that requires early
      aggressive debridement. Any patient with inordinate pain and unilateral edema in
      the pelvis, especially in the puerperium, should be suspected of having this
      disease. Radiographic studies are often diagnostic of this condition. The triad
      of pelvic pain, edema, and any sign of septicemia carries an extremely grave
      prognosis and mandates immediate surgical intervention.

PMID- 12193918
TI  - Factors that are associated with cesarean delivery in a large private practice:
      the importance of prepregnancy body mass index and weight gain.
AB  - OBJECTIVE: The purpose of this study was to examine body mass index and pregnancy
      weight gain as risk factors for primary cesarean delivery in nulliparous women in
      a middle-class private practice. STUDY DESIGN: Primiparous women who delivered in
      a private practice setting between February 1993 and July 13, 2001, were
      included. CIs along with Z statistics for paired count data were used to assess
      the statistical significance and relative importance of the relationships of body
      mass index and maternal weight gain to cesarean delivery. The effect of body mass
      index was examined as related to known confounders such as gestational age, birth
      weight, maternal age, and maternal height. RESULTS: The overall cesarean delivery
      rate for primiparous women was 21.76%. Risk of cesarean delivery increased
      consistently and significantly (P <.0001) with increasing body mass index. This
      effect was primarily mediated through an increase in cesarean delivery carried
      out for cephalopelvic disproportion/failure to progress. In our practice, the
      primiparous woman whose body mass index is >30 kg/m(2) is six times more likely
      to have a cesarean delivery for the diagnosis of cephalopelvic
      disproportion/failure to progress than the primiparous woman whose body mass
      index is <20 kg/m(2). This differential in cesarean delivery rate persisted when
      controlled for birth weight and gestational age and continues to persist when
      maternal age and height are also controlled. Excessive pregnancy weight gain
      exerted a statistically significant effect on cesarean delivery rate. This
      increase was primarily related to cephalopelvic disproportion/failure to progress
      among the nonobese women. CONCLUSION: Maternal body mass index is related
      strongly to the ability of primiparous women to be delivered vaginally without
      great difficulty. In fact, lean patients are excellent labor performers,
      particularly in contrast with obese patients. The relationship of increased body
      mass index to increased cesarean delivery is due to an increased rate of
      cephalopelvic disproportion/failure to progress. Excessive pregnancy weight gain
      is associated with a doubling of cephalopelvic disproportion/failure to progress
      rate in nonobese patients.

PMID- 12193919
TI  - Early intrauterine pregnancy failure: a randomized trial of medical versus
      surgical treatment.
AB  - OBJECTIVE: The purpose of this study was to determine whether medical treatment
      of early pregnancy failure represents a reasonable alternative to surgical
      therapy. STUDY DESIGN: Patients who were diagnosed with pregnancy failure before
      12 weeks of gestation were randomly assigned to receive either medical
      (intravaginal misoprostol) or surgical therapy (dilatation and curettage). In the
      medical arm of the study, 800 microg of misoprostol was placed within the
      posterior vaginal fornix. Patients subsequently were seen 24 and 48 hours after
      the initial dosing; intravaginal misoprostol was readministered only if
      ultrasound images revealed evidence of persistent pregnancy tissue. By 72 hours
      after initial study entry, if either a gestational sac or placental tissue was
      present, the medical treatment was considered a failure, and uterine curettage
      was performed. Statistical analysis was performed with the two-tailed unpaired t
      test, chi(2) analysis, Fisher exact test, and Mann-Whitney U test; a probability
      value of <.05 was considered statistically significant. RESULTS: A total of 50
      women were enrolled, with 2 patients in the surgical arm experiencing spontaneous
      pregnancy loss before their scheduled procedures. Twenty-five women received
      medical therapy; 25 women were randomized to surgical procedure. Fifteen patients
      in the medical group (60%; 95% CI, 0.41-0.79) had successful pregnancy
      termination and did not require curettage. There were no significant differences
      between the medical and surgical groups with respect to either posttreatment
      hematocrit level or the time needed to achieve negative human chorionic
      gonadotropin test results. CONCLUSION: Intravaginal misoprostol is an effective
      agent for the treatment of early pregnancy failure. Medical treatment of early
      pregnancy failure represents a reasonable alternative to immediate surgical
      therapy.

PMID- 12193920
TI  - Prepubertal labial adhesions: evaluation of a referral population.
AB  - OBJECTIVE: The purpose of this study was to assess patient demographics, clinical
      presentation, response to previous treatment, and current evaluation of
      prepubertal girls referred for gynecologic care of labial agglutination. STUDY
      DESIGN: A retrospective chart review of all prepubertal female patients with
      labial agglutination referred from 1996 through 2001. RESULTS: Twenty-three girls
      were diagnosed with labial agglutination during the review period. All of the
      diagnoses were made by a primary care provider. At the time of referral, most
      patients had received medical therapy, but had not obtained resolution of their
      labial agglutination with topical estrogen. Twenty-two of the 23 patients
      required manual separation of the labial adhesions. Findings most frequently
      revealed a pinpoint opening and thick (3-4 mm) adhesions with >90% of the
      vestibule adhered in 21 of 23 girls. Nine of 23 girls had recurrence of
      adhesions. Four girls required a repeat manual separation because of recurrent
      thick adhesions. One of 4 girls required a third manual separation. Five of the 9
      recurrences were treated successfully with topical estrogen. CONCLUSION:
      Gynecologists who treat patients with labial agglutination frequently may
      encounter children for whom medical treatment has failed. Patients whose
      condition does not respond to topical therapy may have thick adhesions and
      require manual separation.

PMID- 12193921
TI  - Review of pregnancy labeling of prescription drugs: is the current system
      adequate to inform of risks?
AB  - Evidence-based medicine that is designed to guide benefit/risk drug therapy
      decisions does not exist for pregnant women. The types of studies that do exist
      are usually conducted in animals, which may not reflect human benefits and risks.
      The types of studies that do exist in humans are typically limited and, at best,
      may show an "association" between a particular drug therapy and an undesirable
      effect. This review outlines the difficulties that are associated with the
      assessment of the benefits/risks of drug therapy during pregnancy, the history of
      the Food and Drug Administration regulations for labeling prescription drugs, and
      the strengths and weaknesses of the current Food and Drug Administration
      pregnancy labeling system. Proposed changes to the current system are reviewed.

PMID- 12193922
TI  - Laparoscopic radical hysterectomy (type III) with aortic and pelvic
      lymphadenectomy in patients with stage I cervical cancer: surgical morbidity and
      intermediate follow-up.
AB  - OBJECTIVE: The purpose of this study was to determine the risk of recurrence and
      to quantify morbidity and mortality rates in patients with cervical cancer who
      consented to undergo laparoscopic radical hysterectomy (type III) and
      retroperitoneal lymphadenectomy. STUDY DESIGN: Seventy-eight consecutive patients
      with stage IA(2) and IB cervical cancer with at least 3 years of follow-up
      consented to undergo this surgical procedure with argon beam coagulation and
      endoscopic staplers. All patients had a Quetelet index of <35. The average age
      was 41.5 years (range, 26-62 years). Sixty-eight patients had squamous cell
      carcinomas; 8 patients had adenocarcinomas, and 2 patients had adenosquamous
      carcinomas of the cervix. RESULTS: All but 5 surgical procedures were completed
      laparoscopically. The average operative time was 205 minutes (range, 150-430
      minutes). The average blood loss was 225 mL (range, 50-700 mL). One patient
      (1.3%) had transfusion. Operative cystotomies occurred for 3 patients: 2
      cystotomies were repaired laparoscopically, and 1 cystotomy required laparotomy.
      One patient underwent laparotomy because of equipment failure, and another
      patient underwent laparotomy to pass a ureteral stent. Two other patients
      underwent laparotomy to control bleeding sites. The average lymph node count was
      34 (range, 19-68). Nine patients (11.5%) had positive lymph nodes. All surgical
      margins were macroscopically negative, but 3 patients had microscopically
      positive and/or close surgical margins. One patient had a ureterovaginal fistula
      after the operation that required reoperation. Follow-up has been provided every
      3 months. There have been 4 documented recurrences (5.1%), with a minimum of 3
      years of follow-up. CONCLUSION: Laparoscopic radical hysterectomy (type III) can
      be successfully completed in patients with early-stage cervical cancer with
      acceptable morbidity. Intermediate-term follow-up validates the adequacy of this
      procedure.

PMID- 12193923
TI  - Baseline inaccuracy rates for the comparison of cervical biopsy to loop
      electrosurgical excision histopathologic diagnoses.
AB  - OBJECTIVE: The purpose of this study was to quantify the baseline inaccuracies in
      histopathologic diagnosis between colposcopically directed cervical biopsies and
      loop electrosurgical excision procedure specimens. STUDY DESIGN: A retrospective
      review was made of cervical biopsies and loop electrosurgical excision procedure
      pairs (n = 448) that were performed at the University of Arizona between 1992 and
      2000. Agreement was assessed by kappa statistics and Spearman rho coefficients.
      Subgroup analysis was performed (n = 139) to assess pairs with significant
      inaccuracy between biopsy and loop electrosurgical excision procedure, when these
      were performed within 28 days of each other. RESULTS: Eighty-one percent
      agreement was found between cervical biopsy and loop electrosurgical excision
      procedure histopathologic diagnoses, when compared to within 1 degree (kappa,
      0.73; P <.0001). A discrepancy that would be attributed to regression or
      progression was found: mild biopsy (regression, none by definition; progression,
      4%), moderate biopsy (regression, 9%; progression, 0%), and severe biopsy
      (regression, 26%; progression, 0%). CONCLUSION: Even when colposcopically
      directed cervical biopsy correlates strongly with loop electrosurgical excision
      procedure histopathologic diagnosis, there is a definable percentage of patients
      for whom there is a discrepancy between these 2 diagnoses. This discrepancy
      represents an inherent inaccuracy of the diagnostic testing modality and should
      not be interpreted as progression or regression of disease.

PMID- 12193924
TI  - Prognostic significance of Bcl-2, p53 overexpression, and lymph node metastasis
      in surgically staged endometrial carcinoma.
AB  - OBJECTIVE: The purpose of this study was to clarify whether Bcl-2 and p53 have
      prognostic significance that is independent of lymph node metastasis and other
      conventional histopathologic factors in endometrial carcinoma. STUDY DESIGN:
      Immunohistochemistry for Bcl-2 and p53 expression was performed on the frozen
      sections of 102 cases that were treated with surgery, including pelvic and para
      aortic lymphadenectomy. Cox regression analysis was used to determine the
      prognostic significance. RESULTS: By univariate analysis, both loss of Bcl-2
      expression and p53 overexpression were related to patient survival. Lymph node
      metastasis, p53 overexpression, and nuclear grade were found to be independent
      prognostic factors (determined by multivariate analysis). The estimated 5-year
      survival rate of patients with stage III/IV disease without p53 overexpression
      was 75.7%; the estimated 5-year survival rate for patients with p53
      overexpression was only 40.4%. The difference was highly significant (P =.0053).
      CONCLUSION: Lymph node metastasis, p53 overexpression, and nuclear grade are
      independent prognostic factors for endometrial carcinoma. Bcl-2 may have little
      importance in the progression of endometrial carcinoma and is a less potent
      prognostic factor than is p53. A new treatment strategy is necessary for advanced
      stage endometrial carcinoma with p53 overexpression.

PMID- 12193925
TI  - High dose-rate intracavitary brachytherapy for carcinoma in situ of the vagina
      occurring after hysterectomy: a rational prescription of radiation dose.
AB  - OBJECTIVE: Our purpose was to profile patients who were treated with high dose
      rate intracavitary brachytherapy for carcinoma in situ of the vagina that
      occurred after hysterectomy, with special reference to a rational prescription of
      radiation dose. STUDY DESIGN: We reviewed 13 patients who were treated for
      posthysterectomy carcinoma in situ of the vagina by the brachytherapy as the sole
      treatment. The brachytherapy was delivered by a remote-controlled afterloading
      intracavitary radiation system. RESULTS: The mean age of the patients was 62
      years. The total dose of absorbed radiation was 36 and 30 Gy that was prescribed
      at 1.0-cm depth to the vaginal surface in 3 cases and at 40 and 30 Gy that was
      prescribed at 0.5-cm depth in 10 cases. All patients had vaginal mucosal
      radiation changes of mild to moderate grade. Three cases that were irradiated to
      a total dose of 30 Gy at 1.0-cm depth had rectal bleeding and/or macroscopic
      hematuria. Complaints regarding sexual functioning were not found in this
      retrospective analysis. All patients remain free of disease after a median follow
      up period of 127 months. CONCLUSION: High dose-rate brachytherapy with a dose
      prescription at 0.5-cm depth can yield a promising rate of tumor control, with
      lower associated morbidity than that with a dose prescription at 1.0-cm depth in
      the treatment of posthysterectomy carcinoma in situ of the vagina.

PMID- 12193926
TI  - Urbanization and baseline prevalence of genital infections including Candida,
      Trichomonas, and human papillomavirus and of a disturbed vaginal ecology as
      established in the Dutch Cervical Screening Program.
AB  - OBJECTIVE: An overgrowth of coccoid bacilli in the absence of lactobacilli
      (bacterial vaginosis) is considered a sign of a "disturbed" vaginal ecologic
      system. The aim of this study was to establish the baseline prevalence of genital
      infections and of a disturbed vaginal ecologic system and their relationship to
      urbanization. STUDY DESIGN: More than 190,000 cervical smears were screened by 1
      cytology laboratory in the context of the Dutch national screening programs. The
      women who were symptom free and had been registered in the statutory files of
      municipal units were screened by invitation. Urbanization (place of residence)
      was derived from the postal code. To investigate a trend in prevalence in
      relation to urbanization, Schaafsma's method was used. RESULTS: Bacterial
      vaginosis had the highest score per 1000 screened women (36.1), followed by
      Candida (12.6). Higher prevalence of human papillomavirus, bacterial vaginosis,
      and Trichomonas was related to urbanization as was, whereas Candida was not.
      CONCLUSION: Human papillomavirus and Trichomonas are more frequently found in
      women who live in the large cities, which in The Netherlands also harbor the high
      risk population for premalignant cytologic evidence. Our findings concerning the
      baseline prevalence pattern of bacterial vaginosis support the hypothesis of the
      importance of a disturbed bacterial ecologic system in cervical carcinogenesis.

PMID- 12193927
TI  - Follicle development in grafted mouse ovaries after cryopreservation and
      subcutaneous transplantation.
AB  - OBJECTIVE: Our aim was to determine the impact of freezing, thawing, and
      subcutaneous transplantation on follicular development in grafted mouse ovaries.
      STUDY DESIGN: The mice were divided into 3 groups: control (group 1), frozen
      thawed grafting (group 2), and frozen-thawed grafting with human menopausal
      gonadotropin injection (group 3). After freezing and thawing, the ovaries were
      transplanted into the subcutaneous tissue. Two weeks after transplantation,
      grafted ovaries and blood samples were collected. RESULTS: Ovaries from group 3
      contained significantly more follicles (246 +/- 43 follicles) than group 2(P
      <.05). The pattern and intensity of Cx37 immunohistochemical staining was similar
      in all groups. Follicle-stimulating hormone concentrations were significantly
      decreased in group 2 after ovarian grafting. CONCLUSION: In mice, gonadotropin
      treatment before subcutaneous grafting improved the survival of growing
      follicles. Subcutaneous ovarian transplantation may restore ovarian function and
      could obviate many of the problems that are related to ovarian banking for
      humans.

PMID- 12193929
TI  - Interstitial laser photocoagulation for uterine myomas.
AB  - Thirty myomas in 24 symptomatic patients who refused conventional surgery were
      treated by interstitial laser photocoagulation, monitored by laparoscopy. The
      procedure was well tolerated. Magnetic resonance imaging or ultrasound scanning
      documented shrinkage in 23 lesions (those lesions >6 cm in diameter responded
      poorly), with clinical benefit in 13 patients.

PMID- 12193928
TI  - 17 beta-Estradiol induces a rapid, endothelium-dependent, sex-specific
      vasodilatation in spontaneous constricted rat arterioles.
AB  - OBJECTIVE: Our purpose was to resolve the apparent contradiction between the
      endothelium-dependent and endothelium-independent vasodilator effects of 17 beta
      estradiol reported in different studies. STUDY DESIGN: The inner diameters of
      isolated pressurized spontaneously constricted muscle arterioles (diameter = 63
      microm) from Wistar rats (n = 21) were measured during exposure to 17 beta
      estradiol, and the role of the endothelium and the influence of sex were
      assessed. RESULTS: A dose-dependent dilatation was observed during exposure to 17
      beta-estradiol concentrations from 10(-10) to 10(-4) mol/L. Arterioles of female
      rats displayed significantly more dilatation than vessels from male rats. The
      dilatation was significantly less in endothelium-denuded arterioles or after
      pretreatment with and in the presence of a nitric oxide synthase inhibitor.
      CONCLUSIONS: These results provide strong evidence that, in addition to an
      endothelium-independent effect, 17 beta-estradiol has a dose-dependent,
      endothelium-mediated, rapid vasodilatory effect on muscle arterioles from the
      rat, which is stronger in female rats than in male rats.

PMID- 12193930
TI  - The differential diagnostic potential of a panel of tumor markers (CA 125, CA 15
      3, and CA 72-4 antigens) in patients with a pelvic mass.
AB  - OBJECTIVE: The purpose of this study was to assess the differential diagnostic
      potential of a combination of CA 125, CA 15-3, and CA 72-4 antigens in the
      definition of malignant disease, especially ovarian carcinoma in patients with a
      pelvic mass. STUDY DESIGN: A total of 412 patients were evaluated in a
      multicenter, retrospective study. RESULTS: Two hundred twenty-six malignant, 171
      benign pelvic tumors (of which 129 were benign ovarian tumors), and 15 borderline
      tumors were evaluated. One hundred thirty-three patients had ovarian carcinoma.
      In 76 cases (55%), the International Federation of Gynecology and Obstetrics
      stage was III or IV. Borderline tumors (n = 15) were excluded from the
      statistical calculations. CA 125 antigen was the most sensitive marker for
      ovarian carcinoma (81%). The highest specificity and positive predictive value
      was obtained with CA 15-3 antigen (95% and 92%, respectively). Considering a
      concomitant elevation of all 3 markers as positive, a positive predictive value
      of 97% was found. However, only 28% of the patients in the total group and 41% of
      the patients with ovarian carcinoma had a concomitant elevation of all 3 markers.
      The combination of all 3 markers with levels below the cut-off resulted in a
      (false-positive) positive predictive value for malignancy between 12% and 36%.
      With the use of logistic regression analysis, we found a correct prediction in
      73% of the cases. CA 15-3 antigen makes the most significant (P <.0001)
      contribution to the logistic model in the prediction of malignancy in the total
      group, with all pelvic masses with an odds ratio of 3.86. CONCLUSION: The
      combination of a simultaneous elevated level of CA 125, CA 15-3, and CA 72-4
      antigens was predictive for malignant disease in almost all cases. However, such
      concomitant elevation was found in few of the malignant masses. Logistic
      regression analysis revealed that CA 15-3 antigen makes the most significant
      contribution to a model for the prediction of malignancy in the total group. The
      logistic model gave a correct prediction in 73% to 83%. The present tumor marker
      panel seems inferior to combinations with other test modalities, which include
      ultrasonography and/or physical examination and/or menopausal status or age.

PMID- 12193931
TI  - A comparison of medical induction and dilation and evacuation for second
      trimester abortion.
AB  - OBJECTIVE: The purpose of this study was to compare complication rates of
      patients who undergo dilation and evacuation or medical abortion between 14 and
      24 weeks of gestation. STUDY DESIGN: We present a retrospective cohort study of
      297 women who underwent either dilation and evacuation or medical abortion.
      Statistical methods included the Student t test, the chi(2) test, the Fisher
      exact test (where appropriate), and logistic regression. RESULTS: The overall
      complication rate was significantly lower in patients who underwent dilation and
      evacuation than in patients who underwent medical abortion (4% vs 29%; P <.001).
      Medical abortions with misoprostol resulted in a lower complication rate than
      abortions with other medications (odds ratio, 0.2; 95% CI, 0.1-0.4). More
      Laminaria was associated with a decreased risk of complications with surgical
      abortions (odds ratio, 0.9; 95% CI, 0.7-1.0). CONCLUSION: Dilation evacuation is
      the safest method of second-trimester abortion. Misoprostol is safer than other
      methods for medical abortion. Maximal use of Laminaria will decrease complication
      rates in surgical abortion.

PMID- 12193932
TI  - Initial neural net construction for the detection of cervical intraepithelial
      neoplasia by fluorescence imaging.
AB  - OBJECTIVE: The aim of this study was to initiate neural net construction for the
      detection of cervical intraepithelial neoplasia by fluorescence imaging. STUDY
      DESIGN: Thirty-three women with abnormal Papanicolaou smears underwent
      fluorescence imaging during colposcopy. With the use of >4000 training pixels and
      >1000 test pixels, intrapatient nets were constructed from the spectral data of
      17 women. An interpatient net that discriminated between cervical intraepithelial
      neoplasia 1 and normal tissue classes among patients was constructed with the use
      of >2300 training pixels and >2000 test pixels from 12 women. Average correct
      classification rates were determined. Sensitivities, specificities, and positive
      and negative predictive values for cervical intraepithelial neoplasia grade 1 and
      normal tissue classes were calculated. Extrapolated false-color cervical images
      were generated. RESULTS: Average correct classification rates were 96.5% for the
      intrapatient nets and 97.5% for the interpatient net. The sensitivity,
      specificity, and positive and negative predictive values for cervical
      intraepithelial neoplasia grade 1 were 98.2%, 98.9%, 71.4%, and 99.9%,
      respectively. CONCLUSION: Initial results suggest that neural nets that are
      constructed from fluorescence imaging spectra may offer a potential method for
      the detection of cervical intraepithelial neoplasia.

PMID- 12193933
TI  - Relationship between levator ani contraction and motor unit activation in the
      urethral sphincter.
AB  - OBJECTIVE: The purpose of this study was to evaluate the relationship between
      levator ani contraction and motor unit action potential activation in the
      striated urethral sphincter. STUDY DESIGN: One hundred eight women who underwent
      preoperative evaluation at our referral center were studied. All women gave a
      urogynecologic history and underwent physical examination, multichannel
      urodynamic testing, and urethral sphincter electromyography. Manual muscle
      testing was used to grade levator ani contractions as poor, moderate, or strong;
      quantitative electromyography software was used to analyze motor unit action
      potential activation in the urethral sphincter. RESULTS: Levator ani contractions
      were graded as poor in 46% of the women, moderate in 31% of the women, and strong
      in 23% of the women. Manual muscle grade was not related to quantitative
      electromyography values in the urethral sphincter at rest or with voluntary
      pelvic floor contraction. Poor manual muscle grade was associated with detrusor
      instability (P =.004) and more advanced stages of prolapse (P =.037). Levator ani
      strength was not significantly related to age, genuine stress incontinence,
      urethrovesical junction hypermobility, menopausal status, or surgical cure rates.
      CONCLUSION: The ability to contract the levator ani does not appear to be related
      to the ability to activate motor unit action potentials in the urethral
      sphincter, which suggests that the function of the levator ani in maintaining
      urinary continence is independent from the role of the urethral sphincter.

PMID- 12193934
TI  - Early surgical abortion: efficacy and safety.
AB  - OBJECTIVE: Because of concern over the higher rates of failed abortion, many
      clinicians defer surgical abortion until 7 menstrual weeks or later. We conducted
      this study to evaluate the efficacy and safety of early surgical abortions that
      are performed by numerous physicians in a community-based setting. STUDY DESIGN:
      We prospectively gathered data on all eligible patients who had surgical
      abortions at <6 weeks of gestation at 3 Planned Parenthood clinics from January
      1, 1998, to August 31, 2000. Outcomes were evaluated with the use of proportions
      with 95% CI and chi(2) analysis. RESULTS: A total of 1132 women had early
      surgical abortions during the study interval, and follow-up was available for 750
      of those women (66%). Seventeen women (2.3%; 95% CI, 1.4%, 3.7%) had failed
      attempted abortions. Other complications occurred in 13 women. CONCLUSION: Early
      surgical abortion is safe and effective. In this series, the frequency of
      complications that required curettage was similar to that reported with
      mifepristone and vaginal misoprostol.

PMID- 12193935
TI  - Abnormal iron parameters in the pregnancy syndrome preeclampsia.
AB  - OBJECTIVE: Our purpose was to investigate iron status parameters in preeclampsia
      with a view to exploring their possible contribution to the etiology. STUDY
      DESIGN: In prepared serum samples from 40 preeclamptic women and matched pregnant
      control subjects at the John Radcliffe Hospital, Oxford, a number of iron status
      parameters were measured. Statistical analysis was by the Wilcoxon signed rank
      test and linear regression. RESULTS: Serum iron concentration, ferritin, and
      percent saturation of transferrin were significantly higher in the preeclamptic
      patients than in control subjects, whereas unsaturated iron-binding capacity and
      apotransferrin levels were significantly lower. No difference was found in
      hemopexin concentrations in the two groups. Gestational age at the time of
      sampling was correlated (positively) with only two parameters, total and
      unsaturated iron-binding capacity, but only in the preeclampsia group. Eighteen
      percent of preeclamptic subjects had percent transferrin saturation levels in the
      region associated with iron overload. CONCLUSION: Released iron species in
      preeclampsia may contribute to the etiology and will exacerbate lipid
      peroxidation and endothelial cell injury. Given the high prevalence of
      heterozygosity for hemochromatosis with the associated reduced ability to exclude
      ingested iron, it would seem inadvisable, in the absence of evidence of iron
      deficiency, to give iron supplements to pregnant women at high risk for
      preeclampsia.

PMID- 12193936
TI  - Magnesium sulfate inhibits the oxytocin-induced production of inositol 1,4,5
      trisphosphate in cultured human myometrial cells.
AB  - OBJECTIVE: The purpose of this study was to determine the effects of magnesium
      sulfate on inositol trisphosphate production and the mechanism of these effects.
      STUDY DESIGN: Myometrium was obtained at the time of cesarean delivery from women
      before labor at term. Inositol trisphosphate was measured in the primary
      myometrial cell cultures after stimulation with oxytocin, sodium fluoride, or Bay
      K 8644 with or without preincubation with magnesium sulfate or nifedipine.
      Experiments were performed in either calcium-containing or calcium-free medium
      that contained egtazic acid and after preincubation with the intracellular
      calcium chelator BAPTA-acetoxymethylester. Inositol trisphosphate production was
      measured by radioreceptor assay. In separate experiments, changes in
      intracellular calcium concentrations ([Ca(2+)](i)) were measured with the use of
      Fura-2 and spectrophotofluorometry. RESULTS: Oxytocin, sodium fluoride, and Bay K
      8644 increased inositol trisphosphate production 2- to 4-fold. Preincubation with
      magnesium sulfate (3 x 10(-3) mol/L) for > or = 5 minutes decreased oxytocin-,
      sodium fluoride-, and Bay K 8644-induced inositol trisphosphate production in
      either calcium-containing or calcium-free media. Preincubation with BAPTA
      acetoxymethylester decreased oxytocin-stimulated inositol trisphosphate
      production by 78% in calcium-containing media and completely prevented the
      oxytocin response in calcium-free media. Magnesium sulfate decreased inositol
      trisphosphate production in calcium-containing media but had no additional effect
      in calcium-free media. Oxytocin and Bay K 8644 increased [Ca(2+)](i) in either
      calcium-containing or calcium-free media, and magnesium sulfate reduced this in
      both cases. CONCLUSION: Magnesium sulfate appears to inhibit phosphatidylinositol
      4, 5-bisphosphate-specific phospholipase C activity and subsequent calcium
      release in cultured myometrial cells by a direct effect on phospholipase C.

PMID- 12193937
TI  - Preeclampsia in the parous woman: who is at risk?
AB  - OBJECTIVE: The purpose of this study was to identify risk factors for
      preeclampsia in second pregnancies and to determine whether gestational age at
      delivery in the first pregnancy increases the risk of recurrent preeclampsia.
      STUDY DESIGN: We conducted a population-based, case-control study using birth
      certificate data from the Missouri maternally linked cohort. Data from women
      delivered of their first 2 singleton pregnancies between 1989 and 1997 (2332
      cases with preeclampsia in the second pregnancy and 2370 control cases) were
      analyzed with logistic regression. RESULTS: Significant risk factors for
      preeclampsia in a second pregnancy include longer birth interval, previous
      preterm delivery, previous small-for-gestational-age newborn, renal disease,
      chronic hypertension, diabetes mellitus, obesity, black race, and inadequate
      prenatal care. Smoking and same paternity are protective. A history of
      preeclampsia confers the highest risk for preeclampsia in the second pregnancy;
      the risk is inversely proportional to gestational age at delivery of the first
      pregnancy: adjusted odds ratio, 15.0; 95% CI, 6.3-35.4 for 20 to 33 weeks;
      adjusted odds ratio, 10.2; 95% CI, 6.2-17.0 for 33 to 36 weeks; and adjusted odds
      ratio, 7.9; 95% CI, 6.3-10.0 for 37 to 45 weeks. CONCLUSION: The relative risk of
      recurrent preeclampsia increases with earlier gestational age at delivery of the
      first pregnancy that was complicated by preeclampsia.

PMID- 12193938
TI  - Factors that are associated with clinically overt postpartum urinary retention
      after vaginal delivery.
AB  - OBJECTIVE: This study was undertaken to determine the incidence of clinically
      overt postpartum urinary retention after vaginal delivery and to examine what
      maternal, fetal, and obstetric factors are associated with this problem. STUDY
      DESIGN: This was a retrospective case-controlled study of women who had overt
      postpartum urinary retention after vaginal delivery from August 1992 through
      April 2000. RESULTS: Fifty-one of 11,332 (0.45%) vaginal deliveries were
      complicated by clinically overt postpartum urinary retention. In most cases
      (80.4%), the problem had resolved before hospital dismissal. Persons with urinary
      retention were more likely than control subjects to be primiparous (66.7% vs
      40.0%; P <.001), to have had an instrument-assisted delivery (47.1% vs 12.4%; P
      <.001), to have received regional analgesia (98.0% vs 68.8%; P <.001), and to
      have had a mediolateral episiotomy (39.2% vs 12.5%; P <.001). On multivariate
      logistic regression analysis, of these 4 variables, only instrument-assisted
      delivery and regional analgesia were significant independent risk factors.
      CONCLUSION: Clinically overt postpartum urinary retention complicates
      approximately 1 in 200 vaginal deliveries, with most resolving before hospital
      dismissal. Factors that are independently associated with its occurrence include
      instrument-assisted delivery and regional analgesia.

PMID- 12193939
TI  - Regulation of connexin 43 by nitric oxide in primary uterine myocytes from term
      pregnant women.
AB  - OBJECTIVE: Our purpose was to test the hypothesis that nitric oxide signals
      regulate the expression of the gap-junction protein connexin 43 in primary
      uterine myocytes from pregnant women at term. STUDY DESIGN: Northern analysis and
      immunoblotting were used to determine the expression of connexin 43 in myocytes
      cultured in the presence of the nitric oxide donors S -nitroso-N -acetyl
      penicillamine (SNAP) (100 micromol/L) and (Z)-1-[2-(2-aminoethyl)-N -(2
      ammonioethyl)amino]diazen-1-ium-1,2-diolate diethylenetriamine (NOC-18) (100
      micromol/L). We also tested the effect of the NO stimulants 8-bromo-cyclic
      adenosine 3',5'-monophosphate (cAMP) (100 micromol/L) and 8-bromo-cyclic
      guanosine 3',5'-monophosphate (cGMP) (200 micromol/L), and the nitric oxide
      synthase inhibitors N -nitro-L-arginine methyl ester (NAME) (100 micromol/L) and
      L -N (1-iminoethyl)lysine (NIL) (50 micromol/L). RESULTS: Nitric oxide and 8
      bromo-cAMP reduced the level of connexin 43 expression, and 8-bromo-cGMP had no
      effect. In contrast, NIL, but not NAME, increased the levels of connexin 43
      protein without affecting the level of connexin 43 messenger RNA. With
      immunoblotting, expression of inducible nitric oxide synthase was not detected in
      these cells. CONCLUSION: Nitric oxide down-regulates the expression of connexin
      43 in cultured human myocytes. We speculate that this effect may decrease the
      efficacy of intermyocyte signaling and thus contribute to uterine quiescence
      during human pregnancy.

PMID- 12193940
TI  - Nutrient intake and congenital heart defects in maternal phenylketonuria.
AB  - OBJECTIVE: The purpose of this study was to determine whether nutritional
      components other than high maternal blood phenylalanine levels (> or = 10 mg/dL)
      are associated with congenital heart defects in the offspring of women with
      hyperphenylalaninemia. STUDY DESIGN: Of the 414 subjects who had live births, 249
      women (60.1%) started diet treatment before 8 weeks of gestation and had
      nutritional assessments and infant outcome data. Maternal phenylalanine levels,
      protein intake, and the incidence of congenital heart defects were determined.
      Simple contingency table analysis was done by chi(2) and Fisher exact test.
      RESULTS: A significantly increased incidence of congenital heart defects was
      observed in offspring of mothers with hyperphenylalaninemia who had an elevated
      blood phenylalanine level >10 mg/dL at 0 to 8 weeks of gestation and a protein
      intake of < or = 50% of the recommended dietary allowance (P <.0013). CONCLUSION:
      An inadequate intake of protein during pregnancy in conjunction with elevated
      blood phenylalanine levels appear to have an additive effect in the incidence of
      congenital heart defects in the offspring of women with hyperphenylalaninemia.

PMID- 12193941
TI  - Ultrasound-indicated cervical cerclage: outcome depends on preoperative cervical
      length and presence of visible membranes at time of cerclage.
AB  - OBJECTIVE: The purpose of this study was to assess cases of ultrasound-indicated
      cervical cerclage and to relate preoperative cervical length, operative findings,
      postoperative cervical length, and pregnancy outcome to establish the appropriate
      criteria to offer cervical cerclage. STUDY DESIGN: A prospective observational
      study comprised 380 women at high risk of preterm labor who underwent serial
      transvaginal ultrasonographic assessment of cervical length. Seventy-three women
      had criteria for and underwent cervical cerclage. Data concerning preoperative
      cervical length, operative findings, postoperative cervical length, and pregnancy
      outcome were collected. Statistical analysis was performed with Mann-Whitney and
      Fisher exact tests. RESULTS: There was a significant increase in median cervical
      length after cerclage, 15.0 versus 25.0 mm (P <.0001). Preoperative cervical
      length and postoperative upper cervical length were independently better
      predictors of outcome than postoperative entire cervical length. Fetal membranes
      were visible in 18% of cases at the time of suture insertion, which was
      associated with a significantly worse outcome, regardless of preoperative
      cervical length. Of those 41 women with a very short preoperative cervical length
      (< or = 15 mm), outcome was significantly worse in those women with visible fetal
      membranes at the time of cerclage compared with those women with no visible fetal
      membranes at the time of cerclage: median gestational age at delivery, 23 weeks
      versus 37 weeks 4 days (P =.002); suture insertion to delivery interval, 19 days
      versus 108 days (P =.0004); and fetal survival rates, 50% versus 86% (P =.03).
      CONCLUSION: In a high-risk population that undergoes serial transvaginal
      ultrasound surveillance of cervical length, the presence of visible fetal
      membranes at the time of suture insertion, regardless of preoperative cervical
      length, is associated with a poor outcome. Fetal membranes were not visible in
      any cases with a preoperative cervical length of >15 mm. These findings lend
      support to a practice of offering cerclage at or above a cervical length of 15
      mm.

PMID- 12193942
TI  - Microparticle subpopulations are increased in preeclampsia: possible involvement
      in vascular dysfunction?
AB  - OBJECTIVE: The purpose of this study was to investigate the cellular origin and
      numbers of circulating microparticles in normal pregnancy and preeclampsia. STUDY
      DESIGN: Plasma samples from 10 women with preeclampsia, from 10 normal pregnant
      women, and from 10 nonpregnant women matched for age and gestation, were analyzed
      by flow cytometry. RESULTS: The total number of circulating microparticles was
      unaltered in pregnancy and preeclampsia. The largest portion of microparticles
      was derived from platelets in all groups. T-suppressor cell microparticle numbers
      were decreased in normal pregnancy (P =.04). In preeclampsia T-suppressor, T
      helper cell, and granulocyte microparticle numbers were increased (P =.008,.008,
      and.03, respectively). Elastase concentrations were increased in preeclampsia (P
      =.02) and correlated with granulocyte microparticle numbers (P =.006). Elastase
      concentrations correlated with systolic and diastolic blood pressure (P =.001
      and.003, respectively), and granulocyte microparticle numbers correlated with
      systolic blood pressure (P =.05). CONCLUSION: Numbers of T-cell and granulocyte
      microparticles are increased in preeclampsia. Whether these altered microparticle
      numbers cause vascular dysfunction in preeclampsia or are a consequence of the
      disease remains to be established.

PMID- 12193943
TI  - Gene expression profile of trisomy 21 placentas: a potential approach for
      designing noninvasive techniques of prenatal diagnosis.
AB  - OBJECTIVE: The purpose of this study was to evaluate the feasibility of the DNA
      microarray technology for the study of the differences in gene expression between
      placentas of pregnancies with trisomy 21 fetuses and placentas of fetuses with a
      normal karyotype. STUDY DESIGN: Complementary DNA samples from 7 second-trimester
      placentas of fetuses with trisomy 21 was compared with 7 matched and 7 nonmatched
      complementary DNA samples from normal karyotype placentas as control samples. For
      gene expression comparison, a microarray that contained 8976 expressed sequence
      tags was used. Four experiments were performed: (1) the study samples were
      compared with matched control samples; (2) the study samples were compared with
      nonmatched control samples; (3) the study samples were compared with themselves;
      and (4) the matched and nonmatched control samples were compared. Gene
      overexpression and underexpression were defined as sample signal differences of
      >1.7 over each other. Gene overexpression and underexpression were confirmed by
      Northern blotting studies. RESULTS: Seven expressed sequence tags of 8976 tags
      that were examined have met the selection criteria. Overexpression of 2 expressed
      sequence tags in placentas with trisomy 21 was confirmed by Northern blotting
      studies. CONCLUSION: Our study demonstrates the feasibility of the microarray
      technique in the study of the differences of gene expression in trisomic
      placentas compared with placentas with a normal karyotype. This technique may
      contribute to the identification of additional maternal serum biochemical markers
      in aneuploid pregnancies.

PMID- 12193944
TI  - Contribution of nonendothelial nitric oxide to altered rat uterine resistance
      artery serotonin reactivity during pregnancy.
AB  - OBJECTIVE: The aims of this study were to evaluate the effects of pregnancy on
      the serotonin reactivity of the mesometrial arteries and to assess the relative
      contribution of endothelial and smooth muscle cells to the overall effect. STUDY
      DESIGN: Arteries were obtained from nonpregnant (n = 20) and late pregnant (n =
      28) Sprague-Dawley rats and were cannulated in the chamber of an arteriograph.
      Changes in lumen diameter were measured by a video dimension analyzer.
      Statistical analysis used 2-way analysis of variance, followed by Bonferroni
      test. RESULTS: Intact vessels from late pregnant versus nonpregnant animals were
      significantly less sensitive to the constrictor effects of serotonin at
      concentrations <100 nmol/L. A role for endothelial nitric oxide was indicated on
      the basis of the effects of denudation and N(omega)-nitro-L-arginine.
      Furthermore, the additional effect of N(omega)-nitro-L-arginine in denuded
      vessels from pregnant animals suggests that another, nonendothelial source of
      nitric oxide also contributes to the effect. CONCLUSION: Pregnancy significantly
      decreases uterine resistance artery sensitivity to serotonin. This difference in
      sensitivity is due to the enhanced production of nitric oxide by endothelial
      cells and, most likely, by vascular smooth muscle.

PMID- 12193946
TI  - Prenatal T-cell reconstitution after in utero transplantation with fetal liver
      cells in a patient with X-linked severe combined immunodeficiency.
AB  - OBJECTIVE: Fetuses with severe combined immunodeficiency may be treated with
      intrauterine transplantation of fetal hematopoietic stem cells. In previous
      reports on intrauterine transplantation with T-cell-depleted bone marrow,
      repeated injections have led to partial immunoreconstitution at birth, with
      subnormal T-cell counts and a delayed response to mitogens. STUDY DESIGN: A male
      fetus with X-linked severe combined immunodeficiency because of a stop mutation
      in the gene encoding the common gamma chain of cytokine receptors was
      transplanted in week 14 of gestation with a single injection of 7 x 10(7)
      cryopreserved nucleated fetal liver cells (9 x 10(8) cells per estimated kilogram
      fetal weight) into the fetal abdomen. At 24 and 33 weeks of gestational age,
      fetal blood samples were taken to detect evidence of engraftment. Fetal mixed
      chimerism was determined using polymerase chain reaction amplification of a
      variable number of tandem repeats and was verified by genomic HLA class II typing
      and flow cytometry. RESULTS: The course of pregnancy, delivery, and the first 18
      months of life have been uncomplicated. At week 24 of gestation, donor HLA class
      II alleles were detected at a low level in the background of the recipient's
      fetal HLA genotype. The chimeric proportion of donor cells was about 10% at 24
      weeks of gestation, increasing to 50% at 33 weeks of gestation. Whereas the T
      cell fraction was still markedly reduced in week 24, it increased thereafter and
      was in the normal range from week 33 of gestation. In vitro response to T-cell
      mitogens was normal from birth. CONCLUSION: In utero transplantation of
      cryopreserved fetal liver cells in week 14 of gestation with a single injection
      led to complete T- and NK-cell reconstitution at birth. Signs of engraftment were
      found already in week 24 of gestation. We consider intrauterine transplantation a
      valuable experimental method and a useful adjunct to postnatal transplantation
      and gene therapy in the treatment of severe combined immunodeficiency.

PMID- 12193945
TI  - Inefficient transduction of sheep in utero after intra-amniotic injection of
      retroviral producer cells.
AB  - OBJECTIVE: Our purpose was to test the hypothesis that the intra-amniotic
      injection of a retroviral vector producer cell line into pregnant sheep will
      result in retrovirus-mediated transduction and stable gene transfer to the ovine
      fetus. STUDY DESIGN: Thirteen pregnant ewes at various gestational ages underwent
      amniocentesis and injection of cells producing the retrovirus vector LIRESgeo,
      which is derived from Maloney murine leukemia virus and encodes Escherichia coli
      LacZ (beta-galactosidase) as a marker gene. Pregnant ewes and fetuses were
      killed, and amniotic fluid, placenta, and fetal tissues were collected and
      assayed for transgene expression 7 to 77 days after intraamniotic injection. In
      addition, serum was collected and analyzed for evidence of specific immune
      responses against the producer cells, and amniotic fluid was collected and
      analyzed for deleterious effects on producer cell viability, vector production,
      and vector transduction. RESULTS: Only 1 of 10 fetuses exposed to the retroviral
      producer cells demonstrated beta-galactosidase activity that correlated with
      positive immunohistochemistry for LacZ in lung, trachea, pancreas, and small
      intestine. However, the presence of the LacZ gene could not be confirmed by
      polymerase chain reaction. Thus, we could not confirm transduction after any of
      the injections. The retroviral producer cells survived well in amniotic fluid and
      continued to produce high levels of retroviral vector after intra-amniotic
      injection, although amniotic fluid inhibited the transducing activity of the
      vector in a manner dependent on gestational age. CONCLUSIONS: Intra-amniotic
      retroviral gene transfer with the use of these amphotropic producer cells does
      not result in reproducible gene transfer in the ovine fetus although amniotic
      fluid sustains producer cell viability and vector production. Possible reasons
      for the inefficient transduction are discussed.

PMID- 12193947
TI  - Cohort study of the neonatal outcome of twin pregnancies that were treated with
      prophylactic or rescue antenatal corticosteroids.
AB  - OBJECTIVE: The purpose of this study was to compare the neonatal outcome of 2
      approaches to antenatal corticosteroid therapy for threatened preterm delivery in
      twins: a prophylactic approach in which corticosteroids were administered every 2
      weeks from 24 to 32 weeks of gestation and a rescue approach in which
      corticosteroids were given to women at immediate risk of preterm delivery. STUDY
      DESIGN: A retrospective cohort study of 1038 twin babies delivered between 1990
      and 1996 in a University Teaching Hospital. One hundred thirty-six babies were
      exposed to prophylactic therapy, and 902 babies were treated expectantly with
      rescue therapy. RESULTS: Prophylactic corticosteroids were not associated with a
      significant reduction in respiratory distress syndrome (adjusted odds ratio, 0.7;
      95% CI, 0.2-2.0). Unnecessary therapy was more likely with a prophylactic policy
      (relative risk, 7.5; 95% CI, 5.3-10.7) and was associated with a reduction in
      mean birth weight in term babies of 129 g (95% CI, -218 to -33; P =.008).
      CONCLUSION: Prophylactic corticosteroids have no proven beneficial effect on the
      risk of respiratory distress syndrome in preterm twin babies. Such a policy
      exposes a large number of babies to unnecessary treatment that adversely affects
      growth.

PMID- 12193948
TI  - Placental types and twin-twin transfusion syndrome.
AB  - OBJECTIVE: The purpose of this study was to assess the value of a proposed
      classification of monochorionic placenta in reference to twin-twin transfusion
      syndrome. STUDY DESIGN: The placentas from laser-treated patients with twin-twin
      transfusion syndrome and from uncomplicated monochorionic pregnancies that were
      delivered between January 1997 and December 2000 were included in the study.
      Placentas were classified as type A (no anastomoses), type B (only deep
      anastomoses), type C (only superficial anastomoses), and type D (deep and
      superficial anastomoses). The number and type of anastomoses were documented in
      each placental type. The severity of twin-twin transfusion syndrome was assessed
      in stages, as previously described. The relationship between placental types and
      the development and severity of twin-twin transfusion syndrome was determined.
      RESULTS: One hundred thirty-one placentas were examined. Twin-twin transfusion
      syndrome developed in 0% (0/4 placentas) of type A, in 100% (85/85 placentas) of
      type B, in 5.6% (1/18 placentas) of type C, and in 79.17% (19/24 placentas) of
      type D placentas. An average of 4.17 (range, 1-11) vascular anastomoses was
      found. The mean number of superficial anastomoses was not different between
      patients with twin-twin transfusion syndrome and patients with no twin-twin
      transfusion syndrome (1.6 vs 1.71, respectively; P =.69, Student t test). The
      presence or absence of superficial anastomoses was not associated with
      differences in the severity of twin-twin transfusion syndrome. CONCLUSION: This
      classification represents a practical approach to the surgical pathologic
      assessment of vascular anastomoses in monochorionic placentas, with a strong
      clinical correlation. It also allows for the clarification of the relationship
      between superficial anastomoses and twin-twin transfusion syndrome.

PMID- 12193949
TI  - Antepartum use of antibiotics and early-onset neonatal sepsis: the next 4 years.
AB  - OBJECTIVE: The purpose of this study was to analyze the incidence of early-onset
      neonatal sepsis and the presence of antibiotic resistance of the isolated
      bacteria and its relationship to antibiotic chemoprophylaxis that occurred during
      the 4 years that followed the publication of the most recent group B
      streptococcal guidelines. STUDY DESIGN: A prospective cohort study was performed
      between January 1, 1997, and December 31, 2000. All cases of early-onset neonatal
      sepsis were gathered prospectively. Data concerning the use of antepartum
      antibiotics, the isolated bacteria, and the presence of drug resistance were
      collected. These data were analyzed separately and were combined with published
      data from the preceding 6 years. RESULTS: A total of 26 cases of blood culture
      proved early-onset neonatal sepsis occurred during the current 4-year study
      period. Group B Streptococcus was responsible for 10 cases, and the remaining 16
      cases were non-group B streptococcal organisms. Of these 16 cases, 11 parturients
      received antibiotic chemoprophylaxis, and 10 of the isolates (91%) were resistant
      to the drug that was administered, compared with only one resistant bacteria
      (20%) in the 5 parturients who did not receive treatment (P =.01). In combining
      these 16 cases with the cases from the preceding 6 years, a total of 43 cases of
      non-group B streptococcal sepsis occurred in 49,788 deliveries. Of these, 26
      mothers were given antepartum antibiotics, and 23 of the bacterial isolates (88%)
      exhibited resistance, compared with only 3 of the 17 cases (18%) in which
      antibiotics were not dispensed (P <.00001). However, because the overall use of
      antepartum antibiotics increased over time, the attack rate for early-onset group
      B Streptococcus significantly decreased by 75% (P <.000001). CONCLUSION: When
      early-onset neonatal sepsis develops in a case in which antepartum
      chemoprophylaxis was used, the bacterial isolate will most likely demonstrate
      resistance to the antibiotic that was administered. However, the development of
      early-onset group B streptococcal neonatal sepsis significantly decreased as the
      use of antepartum antibiotics increased. Thus, the number of prevented infections
      from antepartum antibiotic use may still outweigh the problems that are seen when
      resistant bacterial infections arise. Nevertheless, based on the current
      protocols, a large number of parturients are candidates for antibiotic
      chemoprophylaxis and this, in conjunction with the global concern of bacterial
      drug resistance, should be motivation to examine alternative methods, such as
      vaginal washing or immunotherapy, for decreasing infection.

PMID- 12193950
TI  - Health-related quality of life measurement in women with common benign
      gynecologic conditions: a systematic review.
AB  - Endometriosis, menorrhagia, chronic pelvic pain, and polycystic ovary syndrome
      are major sources of psychologic morbidity and can negatively affect quality of
      life. Although comparative studies have been published on the measurement of
      health-related quality of life for gynecologic malignancies, a similar review for
      these benign gynecologic conditions has not been conducted. Consequently, we
      searched the literature systematically to identify the impact of symptoms and
      treatments for these conditions on health status and to report on the types and
      psychometric properties of the instruments used. Papers were retrieved by
      systematically searching 6 electronic databases and hand-searching relevant
      reference lists and bibliographies. Forty-six studies used a questionnaire to
      measure health status: 34 studies (74%) used standardized instruments; of these,
      23 studies (68%) used generic tools. Although a meta analysis was not possible,
      it appears that women with chronic pelvic pain and conditions that are associated
      with pelvic pain (such as endometriosis) report worse health-related quality of
      life. Despite the development of disease-specific questionnaires, only 2
      questionnaires were generated from interviews of patients with the condition of
      interest, and few questionnaires are being used to evaluate the outcomes of
      treatment on subjective health status.

PMID- 12193951
TI  - Cooper's ligament urethrovesical suspension for stress incontinence. Nine years'
      experience -- results, complications, techniques. 1968.

PMID- 12193952
TI  - Differences in cerclage management lead to different outcomes.

PMID- 12193953
TI  - Usefulness of 3-dimensional color Doppler imaging in the diagnosis and management
      of placenta percreta.

PMID- 12193954
TI  - The use of oxytocin administration to manage the third stage of labor.

PMID- 12193955
TI  - Pregnancy loss after successful laser surgery for previable twin-twin transfusion
      syndrome.

PMID- 12193956
TI  - The G-spot: some missing pieces of the puzzle.

PMID- 12193957
TI  - The G-spot: a modern gynecologic myth.

PMID- 12193958
TI  - The G-spot.

PMID- 12193959
TI  - Case:control association studies of complex disease: is the search for genetic
      determinants a fishing expedition?

PMID- 12193960
TI  - Association between an atrial natriuretic peptide gene polymorphism and normal
      blood pressure in subjects of African ancestry.
AB  - AIM: The roles of the atrial natriuretic peptide (ANP) gene and the clearance
      receptor of the ANP (NPRC) gene in hypertensive groups of African ancestry are
      unclear. The aim of the present study was to assess the relationship between both
      ANP and NPRC gene polymorphisms and hypertension in Black South Africans.
      METHODS: 298 patients, diagnosed as having essential hypertension according to 24
      hour ambulatory blood pressure (BP) measurements (mean daytime diastolic BP> 90
      mm Hg) whilst off medication, and 278 normotensive control subjects of a similar
      African ancestry, were genotyped for polymorphic markers in intron 2 (which is in
      complete linkage disequilibrium with a potentially functional exon 1 variant) and
      exon 3 (which leads to the extension of ANP by two additional arginines) of the
      ANP gene. Moreover, 64 hypertensives and 63 control from the same groups were
      genotyped for the cis-acting promoter/enhancer element of the NPRC gene. RESULTS:
      No relationship between the exon 3 variant and either the presence (odds ratio =
      1.075) or the severity (24-hour BP) of hypertension was noted. The intron 2
      polymorphism occurred at a low frequency in the control group (frequency of
      subjects heterozygous for the variant = 6.1%), but was almost absent in the
      hypertensive group (frequency of heterozygotes = 1.7%). Consequently, a
      relationship between a normal BP and the intron 2 variant was noted (odds ratio =
      0.28, confidence interval = 0.10-0.76, p < 0.01, <1% chance of false positive
      results). The NPRC gene variant occurred with an equally low frequency in both
      the hypertensive (4.7%) and the control (4.8%) groups. CONCLUSIONS: The results
      of the present study suggest that the ANP, but not the NPRC locus contributes to
      BP in subjects of African ancestry.

PMID- 12193962
TI  - Fontan procedure for univentricular hearts: have changes in design improved
      outcome?
AB  - The Fontan operation has undergone numerous design changes in the last 30 years,
      which have resulted in an improved morbidity and mortality of patients with a
      univentricular heart. However, good patient selection and a staged approach to
      the Fontan operation have also contributed greatly to a better outcome in these
      patients.

PMID- 12193961
TI  - Increased glycolysis during ischaemia mediates the protective effect of glucose
      and insulin in the isolated rat heart despite the presence of cardiodepressant
      exogenous substrates.
AB  - BACKGROUND: Exogenous insulin is known to protect against ischaemia-reperfusion
      injury of the myocardium. We investigated whether these benefits of insulin could
      be explained by increased glycolysis during the ischaemic period, even in the
      presence of potentially cardiodepressant substrates such as fatty acids and
      lactate. Increased cardiac output during post-ischaemic reperfusion was used as a
      marker of protection by insulin. METHODS: Isolated hearts from fasted rats were
      subjected to 5 minutes of Langendorff perfusion followed by a 15-minute working
      heart pre-ischaemic perfusion with glucose (11 mmol/l), followed by a 30-minute
      0.2 ml/min low-flow Langendorff ischaemic period, using glucose(11 mmol/l) or
      glucose plus fatty acids (1 mmol/l), or lactate (10 mmol/l), or lactate plus
      glucose as substrates. During reperfusion, the hearts were again perfused with
      glucose. Insulin (1 mU/ml), when added, was present throughout the experimental
      protocol. RESULT: Post-ischaemic reperfusion cardiac output recovery was
      depressed in hearts perfused with glucose plus fatty acids or with lactate alone,
      when compared with glucose alone (p<0.01). In each case, cardiac output improved
      (p < 0.01) with insulin pre-treatment despite added fatty acids, or in hearts
      perfused with lactate alone during ischaemia. Improved cardiac output could be
      linked to improved glucose uptake (p < 0.05) during ischaemia and increased pre
      ischaemic glycogen stores (p < 0.01). In hearts perfused with lactate alone,
      increased glycolysis occurred via glycogen breakdown as confirmed by increased
      cardiac tissue lactate levels at the end o the ischaemic period. CONCLUSION:
      Insulin treatment before ischaemia and throughout ischaemia and reperfusion,
      abolished the depressant effects of fatty acids added to glucose or of lactate
      alone, on reperfusion cardiac output. The consistent feature common to the
      protective effects of insulin in the various conditions tested was increased
      glycolysis, whether achieved by increased glucose uptake during the ischaemic
      period or by glycogen preloading. Increased glycolysis could also explain the
      protective effect of glucose added to lactate in the absence of insulin.

PMID- 12193963
TI  - The occluded coronary artery in the asymptomatic patient after myocardical
      infarction: should it be opened?
AB  - This article reviews the evidence surrounding the "open artery theory": that the
      opening of an occluded artery in an asymptomatic patient after myocardial
      infarction confers survival benefits in excess of the amount of myocardium
      salvaged. Several mechanisms have been proposed in support of the theory, all of
      which remain unproven. The bulk of current knowledge about the open artery is
      drawn from observations on the spontaneous state of patency of the infarct
      related artery and the results of ischaemia-driven intervention. The various
      studies indicate that the advantage of a patent infarct-related artery is
      confined to groups of patients with left ventricular dysfunction or extensive
      (and particularly anterior) infarctions. The largest database that examined the
      effect of the open artery did not find an independent association with survival a
      year after the infarct. The frequency of a totally occluded artery post
      infarction, the lower rate of success in recanalising the vessel, and the high
      rate of reocclusion mediates against a policy of routinely opening the occluded
      vessel. The Occluded Artery Trail is comparing the outcomes in post-infarction
      patients with proximally occluded vessels that supply substantial amounts of
      myocardium randomised to either percutaneous recanalisation or medical therapy.

PMID- 12193964
TI  - Papillary fibroelastoma of the tricuspid valve chordae with a review of the
      literature.
AB  - Endothelial papillary fibroelastomas represent a rare entity in cardiac pathology
      that at times may be associated with embolisation, angina, and sudden death. We
      report on a case of a 46-year-old woman with a papillary fibroelastoma
      originating on the chordae of the tricuspid valve. The tumour was discovered
      incidentally using transthoracic two-dimensional echocardiography. The patient
      had an uneventful recovery and remained free of symptoms after six months.

PMID- 12193965
TI  - Platelet glycoprotein IIb/IIIa receptor blockade with integrilin (eptifibatide)
      for early postinfarction angina in a patient with coronary arterial ectasia.
AB  - A middle-aged male with multivessel proximal coronary ectasia presented with
      thrombosis-related acute myocardial infarction and early postinfarct angina, and
      was successfully treated with a combination of intravenous integrilin
      (eptifibatide) and unfractionated heparin. The possible aetiology, prognosis and
      available management strategies are discussed.

PMID- 12193966
TI  - Generic anti-arrhythmic drugs.

PMID- 12193969
TI  - [Editorial].

PMID- 12193967
TI  - Comment on generic anti-arrhythmic drugs.

PMID- 12193971
TI  - [Fibrinolysis in dysfibrinogenemia].

PMID- 12193970
TI  - [Fibrinogen variation: a heterozygote dysfibrinogenemia with Arg-->His
      substitution in position 16 of the Aalpha chain].

PMID- 12193972
TI  - [Molecular biological basis and diagnosis of hereditary defect of antithrombin
      III, protein c and protein S].
AB  - Recent progress in molecular biology enabled the elucidation of the nucleotide
      sequences of the genes for antithrombin III (AT III), protein C (PROC) and
      protein S (PROS). Furthermore numerous mutations were identified causing genetic
      defects of the important inhibitors of blood coagulation. As the genes for AT III
      (13.8 kb) and PROC (11.2 kb) are small and easy to analyze a great number of
      molecular defects already are described in extensive databases (50, 73): 79
      different mutations for AT III and 160 for PROC are included. The identification
      of mutations leading to AT III and PROC deficiency has given important
      information on the structure-function relationships of the proteins. In case of
      protein C deficiency the clinical relevance of DNA analyses is most important
      because the diagnosis at the protein level is often uncertain. The gene for PROS
      is not so easy to analyze like the other two genes. The PROS gene is large and
      also a PROS pseudogene exists. Although a number of mutations have been
      identified, there has not been published a database until now. The clinical
      relevance to identify gene defects in PROS deficiency is as important as for PROC
      deficiency. Presumably the elucidation of PROS gene defects will advance in the
      near future.

PMID- 12193973
TI  - [APC (activated protein C) resistance].

PMID- 12193974
TI  - [Tissue factor pathway inhibitor: biochemistry, molecular biology, physiology and
      physiopathology].

PMID- 12193975
TI  - [Molecular variants of fibrinogen].
AB  - In the final step of blood coagulation, fibrin monomers polymerize spontaneously
      and are covalently linked by factor XIIIa. Mutations in one of the three genes
      coding for the fibrinogen peptides may disturb this process and lead to diseases
      such as afibrinogenemia or dysfibrinogenemia, or may even cause hereditary renal
      amyloidosis. In the brief overview presented here we summarize some of the
      molecular aspects of these diseases.

PMID- 12193976
TI  - [Loco-regional lysis with thrombosis older than 10 days: experiences and
      outcome].
AB  - Successful treatment of deep vein thrombosis by lysis therapy leads to
      recanalisation of the occluded vessel saving the venous flaps, thus limiting
      postthrombotic syndrome. Systemic lysis therapy carries an increased risk of
      fatal complications (1-2%). However, loco-regional lysis therapy with rtPA stands
      out as a method of recanalisation without increased complications compared to
      compression and anticoagulation therapy. According to the leading opinion about
      systemic lysis therapy it should only be performed if thrombotic age does not
      exceed 10 days. In this study we examined whether loco-regional lysis therapy is
      successful with older thrombosis, too. We showed that in thromboses older than 10
      days lysis success was slightly decreased whereas postthrombotic syndrome doubled
      (up to 50%). These results point out loco-regional lysis as a method suitable for
      thromboses with age up to 10 days only.

PMID- 12193978
TI  - [Factor-XIII-research: Pioneer achievement and progress].

PMID- 12193977
TI  - [Initiation of oral anticoagulant treatment: comparison between different dosage
      regimens of warfarin and phenprocoumon].
AB  - A high "loading dosage" is often given during initiation of oral anticoagulant
      treatment in order to reach sufficient anticoagulation within short time.
      Increased bleeding risk as well as a transient prothrombotic tendency are
      complications of this treatment schedule. The aim of our study was to find proper
      dosage regimens of phenprocoumon and warfarin allowing initiation of oral
      anticoagulant treatment in a short time. For 50% of the patients 7.5 mg warfarin
      daily resulted in stable INR values within 4 days. Patients receiving higher (10
      mg) or lower (5 mg) daily dosages of warfarin or 6 or 9 mg phenprocoumon daily
      during the first days of therapy reached the therapeutic range significantly
      later. Furthermore, no significant differences of prothrombin fragment F 1+2 were
      observed, indicating that no enhanced thrombin formation occurred. Thus,
      initiation of oral anticoagulant treatment using 7.5 mg warfarin daily is a
      simple and safe dosage regimen.

PMID- 12193980
TI  - [Factor XIII in man: a review].
AB  - Activated by calcium and thrombin, factor XIII (FXIIIa) cross-links fibrin, thus
      increasing the stability of the fibrin clot. Furthermore, the hemostatic and
      reparative function of factor XIIIa is mediated by cross-linking other proteins
      like alpha(2)-plasmin-inhibitor, fibronectin, and collagen. The FXIII Val34Leu
      polymorphism plays a role in athero- and thrombogenesis. FXIII deficiency is an
      autosomal recessive disorder. The most common symptom is the bleeding tendency of
      the umbilical cord some days after birth. The diagnosis is confirmed by a
      solubility clot test in urea (5 mol/l) and then differentiated with an
      incorporation assay and immuno-electrophoresis. The bleeding tendency typically
      becomes obvious when FXIIIa activity is <1-2%. Severe bleeding episodes, however,
      may even occur with FXIIIa activities of 30-50%, especially in heterozygous
      persons. The sometimes life-threatening bleeding tendency of the inherited FXIII
      deficiency can be treated with FXIII concentrates. Acquired FXIII deficiency
      occurs in several internal diseases and after major surgery. The clinical
      significance is not completely clear. Moreover, FXIII is applied locally as a
      component of fibrin glues.

PMID- 12193981
TI  - [Blood coagulation factor XIII: activation, substrates and structure of a
      transglutaminase].
AB  - For a long time blood coagulation factor XIII did not get the attention it
      deserves, and research in the field of transglutaminases was neglected. The
      interesting results obtained in recent years demonstrate the importance of this
      protein for the stabilization of a blood clot. The accurate regulation of
      activation and of localization of factor XIII is not fully understood. Yet the
      proposed mechanisms suggest a high degree of complexity. In this review, recent
      biochemical and structural results on factor XIII are discussed.

PMID- 12193982
TI  - [Factor XIII and endothelial barrier function].
AB  - Activated factor XIII (FXIIIa) crosslinks fibrin monomers to a stable clot. Due
      to this function, FXIIIa plays a major role in hemostasis and fibrinolysis.
      Additionally, it is well known that FXIIIa has a special meaning in cell adhesion
      and migration, in generation of extracellular matrix, in tissue repair and wound
      healing. New experimental studies revealed a FXIIIa stabilizing endothelial
      barrier function. In this function, FXIIIa reduces endothelial permeability for
      macromolecules in cultured endothelial monolayers and prevents impending barrier
      failure in coronary arteries of isolated hearts. This effect is due to the cross
      linking of several proteins within the extracellular matrix, especially in the
      interendothelial clefts.

PMID- 12193983
TI  - [Methods for the determination of factor XIII/XIIIa].
AB  - Activated factor XIII (FXIIIa) plays an important role in the final stage of the
      coagulation cascade by covalent crosslinking of fibrin strands. As a
      transglutaminase FXIIIa catalyses the generation of intermolecular amide bonds
      between lysine and glutamine residues resulting in a complex three-dimensional
      clot structure. Enhanced clot stability is supported by covalent binding of
      cytosceleton factors like actin and myosin. Moreover, the clot is protected
      against premature lysis by the incorporation of fibrinolysis inhibitors like
      alpha(2)-antiplasmin and thrombin activatable fibrinolysis inhibitor (TAFI). A
      covalent crosslinking of the fibrin strands with extra-cellular matrix proteins
      like fibronectin, vitronectin, collagen and von Willebrand factor (vWF)
      immobilizes the clot at the site of injury. Moreover FXIII supports the healing
      process of damaged tissue. In this review assays for determination of FXIIIa
      activity, FXIII concentration and identification of the FXIIIVal34Leu
      polymorphism are shown.

PMID- 12193984
TI  - [Inhibitors of factor XIIIa].
AB  - Factor XIIIa (FXIIIa) catalyzes the covalent crosslinking of fibrin polymers and
      incorporation of proteins into the fibrin network and thus confers on the
      thrombus additional structural stability and relative resistance to plasmin
      mediated degradation. Moreover, FXIIIa is involved in other physiological and
      pathophysiological processes such as wound healing and arteriosclerosis.
      Selective FXIIIa inhibitors may be a valuable tool for evaluation of the various
      functions of FXIIIa and their pharmacological control. This paper presents an
      overview of the inhibitors of FXIIIa. Analogues of natural FXIIIa substrates -
      including glutamine containing peptides and low molecular weight substituted
      alkylamines - are incorporated into the fibrin network and thus prevent
      crosslinking of fibrin. Naturally occurring, direct inhibitors of FXIIIa have
      been isolated from a leech species and microorganisms. With effective
      concentrations in the nanomolar range the peptide tridegin is the most potent
      FXIIIa inhibitor up to now. The majority of the synthetic, low molecular Weight
      inhibitors bind covalently to Cys314 at the active site of FXIIIa. Besides the
      relatively nonspecific thiol reagents, azol derivatives, azolium salts and
      related substances are described as specific inhibitors of FXIIIa. They inhibit
      the activity of FXIIIa at nanomolar concentrations. Animal experiments have
      demonstrated improved thrombolysis by a plasminogen activator in combination with
      a FXIIIa inhibitor.

PMID- 12193985
TI  - [Clinical course and management of severe congenital factor XIII deficiency].
AB  - Severe homozygous factor XIII deficiency was first described in Switzerland, in
      1961. At present 14 patients are known here. Nine are of Swiss origin, the others
      are immigrants from eastern Europe. A 27-year-old woman with many haemorrhages
      during childhood immigrated to Switzerland and went through four episodes of
      haemorrhagic corpus luteum cyst rupture with life-threatening blood loss into the
      abdomen and three haemorrhages into the retroperitoneal muscles causing
      sensomotoric palsies, before the diagnosis was established. A monthly
      prophylactic replacement therapy of 500 IE factor XIII concentrate was started.
      Since then no signs of haemorrhage occurred. For the last trimester of pregnancy
      treatment intervals were shortened and dosage increased. Haemorrhage from the
      umbilical cord for weeks, subcutaneous haematomas, intracranial haemorrhage,
      muscle haemorrhage and wound bleeding with impaired wound healing as well as
      tendency to marked scar formation are characteristic for severe homozygous factor
      XIII deficiency. Without replacement therapy women suffer from obligate abortion.
      Diagnosis is made by the solubility of fibrin clots in urea (5 mol/l) or
      monochloroacetic acid (1-2%). For confirmation and monitoring of replacement
      therapy a quantitative incorporation assay is used. Replacement therapy is
      necessary in case of haemorrhage, injury, and surgery. Because of the high risk
      of intracranial haemorrhage prophylaxis is strongly recommended.

PMID- 12193986
TI  - [Role of coagulation factor XIII in cardio- and cerebrovascular diseases].
AB  - In the final step of the clotting cascade coagulation factor XIII (FXIII) is
      activated by thrombin. The activated enzyme (FXIIIa) has an important role in the
      final stage of blood coagulation in cross-linking soluble fibrin to a stable
      insoluble clot. The role of FXIII in cardio- and cerebrovascular diseases has
      been investigated recently. The widespread Val34Leu polymorphism in the gene
      coding for the FXIII subunit A (FXIII Val34Leu) has been shown to protect against
      myocardial infarction and ischemic stroke, but is also associated with an
      increased risk for hemorrhagic stroke. Additionally, FXIII Val34Leu is supposed
      to be protective against pulmonary embolism and deep vein thrombosis. As possible
      mechanisms for the antithrombotic effect, premature depletion of the mutant
      protein from circulation and altered fibrin structures of clots cross-linked by
      the mutant FXIIIa are under discussion. The connection between FXIII and the
      insulin resistance syndrome also attracts attention, i.e. the interaction between
      a component of the coagulation cascade and thus a thrombotic risk factor and
      classical atheromatous risk factors. Therefore, FXIII must be considered as
      another coagulation factor contributing to complex interactions between genes and
      environment important for the pathogenesis of cardio- and cerebrovascular and
      thromboembolic diseases.

PMID- 12193989
TI  - "Spine Tango" spine registry.

PMID- 12193987
TI  - [Factor XIII and wound healing].
AB  - In addition to those wounds with increasing fragility of capillaries during
      impaired healing, there are especially long lasting diabetic wounds or calf
      ulcerations due to chronic venous insufficiency or postthrombotic syndrome that
      show a failure of endothelial barrier function with an increased permeability as
      an important part of its pathophysiological situation. The possibility of
      controlling this increased permeability is of great therapeutical interest and
      may give distinct benefit for wound healing. In the close past, clinical as well
      as experimental studies revealed the plasma transglutaminase (factor XIIIa) as
      potential new strategy in treatment of increased vascular permeability.

PMID- 12193990
TI  - A European spine registry.
AB  - New joint replacement registries are being widely implemented across national and
      international organizations. The need for a continuous long-term post-market
      surveillance of implants has been recognized, and has become increasingly
      important to ensure the quality of prosthetic components. Registry data with
      large case numbers represent an acceptable alternative to controlled randomized
      clinical trials, which are often difficult to conduct in orthopedic surgery. The
      variety of implants and procedures in spinal surgery not only induces the same
      need for long-term monitoring of post-surgical product performance as in the
      joint replacement subspecialties, but also renders essential the establishment of
      a comprehensive spine registry for all major pathologies and interventions. In
      cooperation with the M.E. Muller Institute for Evaluative Research in Orthopedic
      Surgery (MEM-CED) at the University of Berne, Switzerland, the Spine Society of
      Europe (SSE) has launched Spine Tango: the first modular and multilevel European
      online registry for spinal surgery. Within Spine Tango, the major challenge in
      registry design and structure is the definition of and agreement upon a core set
      of questions as a common European dataset. Additional questions for national or
      individual interest can also be dynamically added to the core dataset. An
      automated implant tracking system has also been setup, which allows highly
      precise product documentation without additional work for clinical staff members.

PMID- 12193991
TI  - 2002 SSE Award Competition in Basic Science: expression of major matrix
      metalloproteinases is associated with intervertebral disc degradation and
      resorption.
AB  - During the process of degeneration, the intervertebral disc (IVD) shows a
      progressive and significant reduction in height due to tissue resorption.
      Intradiscal clefts and tears are major hallmarks of disc degeneration. Matrix
      degrading enzymes such as matrix metalloproteinases (MMPs) are assumed to play a
      pivotal role in disc tissue degradation and resorption. The objective of this
      study was therefore to investigate the potential role of MMPs in extracellular
      matrix degradation leading to disc degeneration. This study was conducted on 30
      formalin-fixed and EDTA-decalcified complete cross-sections of lumbar IVDs from
      cadavers of individuals aged between 0 and 86 years. Tissue sections were used
      for the immunolocalization of MMPs-1, -2, -3 and -9. The number of labeled cells
      was assessed by morphometric analyses, and was statistically correlated with the
      formation of clefts and tears, cellular proliferation, granular matrix changes
      and mucous degeneration. Furthermore, 30 disc specimens obtained during spinal
      surgery were used for in situ hybridization of MMP-2 and -3-mRNA. In addition,
      the enzymatic gelatinolytic activity was determined by in situ zymography in
      autopsy material. Immunohistochemistry showed the intradiscal expression of all
      four MMPs, which was confirmed by in situ hybridization, providing clear evidence
      for the synthesis of the enzymes within nucleus pulposus and annulus fibrosus
      cells. Gelatinolytic enzymatic activity was verified by in situ zymography. IVDs
      from infants and young adolescents remained almost completely unlabeled for all
      MMPs tested, while more MMPs-1 and -3 were seen in disc cells of younger adults
      than in those of a more advanced age; MMP-2 remained unchanged over the adult age
      periods, and MMP-9 was expressed in only relatively few cells. This pattern
      significantly correlated with the occurrence of clefts and tears. This
      correlation was strongest for MMP-1 ( P<0.0001), MMP-2 ( P<0.0017) and MMP-3 (
      P<0.0005) in the nucleus, and MMP-1 ( P<0.0001) and MMP-2 ( P<0.038) in the
      annulus. In parallel, the proliferation of disc cells and matrix degeneration
      (granular changes and mucous degeneration) were related to MMP expression.
      Likewise, enzymatic activity was seen in association with cleft formation. Our
      data suggest that major MMPs play an important role in the degradation of the
      IVD. This is evidenced by the high correlation of MMP expression with the
      formation of clefts and tears. These findings implicate a leading function for
      MMPs in IVD degeneration resulting in the loss of normal disc function,
      eventually leading to low-back pain.

PMID- 12193992
TI  - A study of the mechanical stability of scoliosis constructs using variable
      numbers of sublaminar wires.
AB  - Sublaminar wiring with posterior instrumentation is one of the methods used when
      long fusions involving 10-12 thoracolumbar levels are required. Classically,
      wires are used at every consecutive level to make the construct as rigid as
      possible, although complications like dural tears, cerebrospinal fluid leak, and
      neurological deficit have been reported during their passage. We compared the
      mechanical stability under torsional strain of five specimens of each of three
      construct designs, by static and fatigue testing, using an electro-servo
      hydraulic testing machine. In construct A, a contoured Hartshill rectangle was
      used from T2 to L2, with sublaminar wires passed at every level. In construct B,
      the Hartshill rectangle was wired to the spine at every alternate level. In
      construct C, every alternate level was wired except at the proximal end, where
      two consecutive levels were wired. Industrially fabricated spine models were used
      to prepare these constructs. The intervertebral motion within the construct was
      measured using the Fastrak magnetic field sensor device. On static testing, no
      statistically significant difference was found in the rotational displacement of
      the three construct designs. On fatigue testing, all samples of construct B
      consistently failed, with breakage of the wire at the most proximal level on the
      left side. But on adding additional wires to the next level (construct C), all
      five samples withstood fatigue testing at 300 N load to three million cycles. We
      conclude that wiring alternate levels instead of every level does not compromise
      the stability of the construct, provided that the most proximal two levels are
      consecutively wired. This practice would minimise the risk of dural tears and
      cord damage during wire passage and reduce surgical time, not to mention the
      economic benefits.

PMID- 12193993
TI  - Does genotype predict development of the spinal deformity in patients with
      diastrophic dysplasia?
AB  - This study analyzed whether genotype can be used to predict development of spinal
      deformity in patients with diastrophic dysplasia (DD). Severity and natural
      history of scoliosis vary among patients, but the magnitude of the curves is
      similar among siblings. Plain radiographs were taken of 69 patients aged 16 years
      or older. The degree of scoliosis was measured according to Cobb's method. Blood
      samples were collected from patients clinically diagnosed as having DD and the
      genotype was determined. Fifty-six patients were found to be homozygous for the
      Finnish founder DTD mutation, DTDST(Fin). Of these 56, 51 (91%) had scoliosis,
      with an average curve of 43 degrees (range 12 degrees-188 degrees ). The
      DTDST(Fin)/R279 W genotype was found in nine patients, and of these, eight (89%)
      had scoliosis, with an average curve of 34 degrees (range 11 degrees-70 degrees
      ). The DTDST(Fin)/nondetermined genotype was found in four patients. Three (75%)
      of them had scoliosis, with an average curve of 126 degrees (range 77 degrees-188
      degrees ). Statistical analysis found no difference in the prevalence or
      magnitude of curves between subgroups. The development and severity of the
      scoliosis cannot, therefore, be predicted from the genotype. It seems possible
      that scoliosis development is affected by several genes as well as by external
      factors.

PMID- 12193994
TI  - Interface corrective force measurements in Boston brace treatment.
AB  - Brace application has been reported to be effective in treating idiopathic
      adolescent scoliosis. The exact working mechanism of a thoracolumbo spinal
      orthosis is a result of different mechanisms and is not completely understood.
      One of the supposed working mechanisms is a direct compressive force working
      through the brace upon the body and thereby correcting the scoliotic deformity,
      achieving optimal fit of the individual orthosis. In this study we measured these
      direct forces exerted by the pads in a Boston brace in 16 patients with
      idiopathic adolescent scoliosis, using the electronic PEDAR measuring device
      (Novel, Munich, Germany). This is designed as an in-shoe measuring system
      consisting of two shoe insoles (size 8 1/2), wired to a computer, recording
      static and dynamic pressure distribution under the plantar surface of the foot.
      After positioning the inserts between the lumbar and thoracic pads and the body,
      we measured the forces acting upon the body in eight different postures. In all
      positions the mean corrective force through the lumbar brace pad was larger than
      the mean corrective force over the thoracic brace pad. Some changes in body
      posture resulted in statistically significant alterations in the exerted forces.
      There was no significant correlation between the magnitude of the compressive
      force over the lumbar and thoracic brace-pad and the degree of correction of the
      major curve. Comparing the corrective forces in a relatively new (<6 months) and
      old (>6 months) brace, there was no statistically relevant difference, although
      the corrective force was slightly larger in the new braces. We think that the use
      of this pressure measurement device is practicable and of value for studies of
      the working mechanism of brace treatment, and in the future it might be of help
      in achieving optimal fit of the individual orthosis.

PMID- 12193995
TI  - Comparative analysis of pedicle screw and hook instrumentation in posterior
      correction and fusion of idiopathic thoracic scoliosis.
AB  - Posterior correction and fusion with segmental hook instrumentation represent the
      gold standard in the surgical treatment of progressive idiopathic thoracic
      scoliosis. However, there is a debate over whether pedicle screws are safe in
      scoliosis surgery and whether their usage might enable a better curve correction
      and a shorter fusion length. The details of curve correction, fusion length and
      complication rate of 99 patients with idiopathic thoracic scoliosis treated with
      either hook or pedicle screw instrumentation were analyzed. Forty-nine patients
      had been operated with the Cotrel-Dubousset system using hooks exclusively ("hook
      group"). Fifty patients had been operated with either a combination of pedicle
      screws in the lumbar and lower thoracic and hooks in the upper thoracic spine or
      exclusive pedicle screw instrumentation using the Munster Posterior Double Rod
      System ("screw group"). The preoperative Cobb angle averaged 61.3 degrees (range
      40 degrees-84 degrees ) in the hook group and 62.5 degrees (range 43 degrees-94
      degrees ) in the screw group. Average primary curve correction was 51.7% in the
      hook group and 55.8% in the screw group ( P>0.05). However, at follow-up (2-12
      years later) primary curve correction was significantly greater ( P=0.001) in the
      screw group (at 50.1%) compared to the hook group (at 41.1%). Secondary lumbar
      curve correction was significantly greater ( P=0.04) in the screw group (54.9%)
      compared to the hook group (46.9%). Correction of the apical vertebral rotation
      according to Perdriolle was minimal in both groups. Apical vertebral translation
      was corrected by 42.0% in the hook group and 55.6% in the screw group ( P=0.008).
      Correction of the tilt of the lowest instrumented vertebra averaged 48.1% in the
      hook group and 66.2% in the screw group ( P=0.0004). There were no differences
      concerning correction of the sagittal plane deformity between the two groups.
      Fusion length was, on average, 0.6 segments shorter in the screw group compared
      to the hook group ( P=0.03). With pedicle screws, the lowest instrumented
      vertebra was usually one below the lower end vertebra, whereas in the hook group
      it was between one and two vertebrae below the lower end vertebra. Both operative
      time and intraoperative blood loss were significantly higher in the hook group (
      P<0.0001). One pedicle screw at T5 was exchanged due to the direct proximity to
      the aorta. There were no neurologic complications related to pedicle screw
      instrumentation. Pedicle screw instrumentation alone or in combination with
      proximal hook instrumentation offers a significantly better primary and secondary
      curve correction in idiopathic thoracic scoliosis and enables a significantly
      shorter fusion length.

PMID- 12193996
TI  - Three-dimensional surface rendering reconstruction of scoliotic vertebrae using a
      non stereo-corresponding points technique.
AB  - The medical imaging techniques that allow a three-dimensional (3D) surface
      rendering reconstruction, which is usually required by the clinician when dealing
      with scoliotic patients, are computed tomography (CT) and stereoradiography.
      However, CT cannot provide a 3D rendering of the whole spine because of the high
      irradiating dose, while the stereoradiographic 3D reconstruction techniques,
      which use an algorithm derived from the direct linear transformation (DLT), are
      usually limited in accuracy because of the small number of corresponding
      anatomical landmarks identifiable on both radiographs. The purpose of the present
      study is to validate a recent biplanar 3D surface rendering reconstruction
      technique on scoliotic vertebrae. This technique, called "non stereo
      corresponding points" (NSCP), has already been tested on non-pathologic dry
      cervical vertebrae and frozen lumbar specimens, and the results have proved very
      encouraging. Since scoliosis is a 3D deformity of the vertebrae and of the global
      spine, such a technique could be a very useful clinical tool for the diagnostic,
      follow-up and surgical planning when dealing with scoliotic patients. The
      validation of the NSCP technique on scoliotic patients was performed on 58
      scoliotic vertebrae in 14 patients, by comparison with the CT scan 3D rendering
      technique. The results of this study show mean errors of 1.5 mm. On the basis of
      this study, we can conclude that the NSCP 3D reconstruction technique is a
      definite improvement over existing techniques, and can serve as a useful
      diagnosis tool in scoliosis. However, the results of the technique still need to
      be optimized for use in geometrical modeling.

PMID- 12193997
TI  - Computer-assisted Cobb measurement of scoliosis.
AB  - This study was devised to develop a simple computerised method for measuring and
      quantifying the magnitude of spinal curvatures. A digitally scanned antero
      posterior radiographic image was used. The vertebral column was defined as a line
      that can be subdivided into a number of segments, rather than into the exact
      number of vertebrae. The technique developed allows an observer to measure the
      spinal curvature with a high resolution and accuracy. One important advantage of
      the technique is that the assessor does not need to be skilled or experienced in
      measurement of a spinal curvature.

PMID- 12193998
TI  - MRI changes of cervical spine in asymptomatic and symptomatic young adults.
AB  - Several work-related, psychosocial and individual factors have been verified as
      being related to neck and shoulder pain, but the role of pathology visualized by
      magnetic resonance imaging (MRI) remains unclear. In this study, the relationship
      between neck and shoulder pain and cervical high-field MRI findings was
      investigated in a sample of persons in a longitudinal survey. The study aimed to
      determine whether subjects with persistent or recurrent neck and shoulder pain
      were more likely to have abnormal MRI findings of cervical spine than those
      without neck and shoulder pain. A random sample of 826 high-school students was
      investigated initially when the students were 17-19 years, and again when they
      had reached 24-26 years of age. Eighty-seven percent participated in the first
      survey in 1989, of whom 76% took part in the second survey, in 1996. The
      validated Nordic Musculoskeletal Questionnaire was used to collect data about
      neck and shoulder symptoms. Two groups were chosen for the MRI study: the first
      group ( n=15) consisted of the participants who had reported no neck and shoulder
      symptoms in either of the inquiries, while the second group ( n=16) comprised
      those who were suffering from neck and shoulder symptoms once a week or more
      often at the time of both surveys. The degrees of disc degeneration, anular tear,
      disc herniation and protrusion were assessed by two radiologists. The differences
      between the two study groups were evaluated. The study found that abnormal MRI
      findings were common in both study groups. Disc herniation was the only MRI
      finding that was significantly associated with neck pain. These findings indicate
      that pathophysiological changes of cervical spine verified on MRI seem to explain
      only part of the occurrence of neck and shoulder pain in young adults.

PMID- 12193999
TI  - Cotrel Dubousset instrumentation in occipito-cervico-thoracic fusion.
AB  - There are today several techniques available for cervical fixation - all with
      inherent limitations and risks. In view of the drawbacks of wiring and screw
      fixation, which both presuppose good bone quality for stabilization, there is a
      need for a stable and safe fixation system that can also be used in osteoporotic
      bone. The objective of the present retrospective study was to assess the
      usefulness and safety of Cervical Cotrel Dubousset Instrumentation (CCDI), based
      on sublaminar hooks. The material comprises 60 consecutive patients, 28 men and
      32 women, with a mean age of 57.3 years (range 17-84 years), operated on with
      CCDI. The diagnosis was trauma in 17 patients, rheumatoid arthritis in 16
      patients, tumor in 20 patients and miscellaneous diagnoses in 7 patients. The
      material was dominated by severe pathologies, with neurological impairment in 17
      patients (28%). Complications, subjective outcome and Frankel classification of
      neurological status pre- and postoperatively was documented. The patient outcome
      evaluation was excellent in 46%, good in 34%, fair in 10%, and poor in 10%. The
      physician's assessment was similar: 56% excellent, 27% good, 10% fair and 7%
      poor. Two patients improved by two Frankel grades, 7 by one and 47 patients had
      the same Frankel grade as preoperatively. Two patients deteriorated by one
      Frankel grade, one by three grades and one patient by four Frankel grades. Except
      for a 10% deep wound infection rate, there were few complications, with no
      evidence of neurological injury from the hooks in the spinal canal. The results
      of this study show that the cervical CDI system can be safely used for stable
      cervical fixation without need for external support in severe pathologies of the
      cervical spine.

PMID- 12194000
TI  - Do worker's compensation patients with neck pain have lower SF-36 scores?
AB  - Poorer outcomes of treatment are reported in patients with spinal disorders who
      receive worker's compensation. The reason for their suboptimal outcomes is
      unclear. No study has examined the relationship between worker's compensation and
      SF-36 health status of patients with neck pain. The aim of our study was to
      compare the self-perceived health status of patients with neck pain receiving
      worker's compensation, with that of patients not receiving worker's compensation.
      A cross-sectional study was conducted on 2356 patients with neck pain who were
      evaluated at the 27 centers comprising the National Spine Network, between
      January 1998 and April 2000. The outcome measures used were the eight individual
      and two component scores of the SF-36 health survey. Of the 2356 patients, 171
      (7%) were receiving worker's compensation. Bivariate analyses revealed seven
      individual scores (except General Health) and two summary scores of the SF-36
      were significantly lower in patients receiving worker's compensation. After
      controlling for confounding covariates, worker's compensation status was a
      significant predictor of lower SF-36 scores for Physical Functioning ( P<0.05).
      The results of this study indicate that worker's compensation status is
      associated with poorer Physical Functioning in patients presenting with neck
      pain. Another significant finding of the study is that confounding factors can
      exert major effects on the SF-36 scores obtained on normal validated instruments.

PMID- 12194001
TI  - Regional differences within the human supraspinous and interspinous ligaments: a
      sheet plastination study.
AB  - The extent to which neighboring muscles and the fascia contribute to the
      formation of the supraspinous and interspinous ligaments is not clear from the
      literature. The purpose of this investigation is to examine the midline
      attachments of tendons and the posterior layer of thoracolumbar fascia in order
      to determine their respective contributions to the formation of these ligaments
      throughout the thoracolumbar spine. Study of the dense connective tissue
      organization in the posterior ligamentous system was carried out on two cadavers
      serially sectioned into thin (2.5-mm) epoxy resin plastinated slices. Additional
      observations were taken from a gross anatomical study of the midline anatomy in
      two adult cadavers. The results show that the spinal attachments of trapezius,
      rhomboideus major and splenius cervicis combine with the deep fascia to form the
      supraspinous ligament in the upper thoracic spine. The posterior layer of the
      thoracolumbar fascia makes a major contribution to the supraspinous and
      interspinous ligaments in the lower thoracic spine. In addition to the posterior
      layer of thoracolumbar fascia, longissimus thoracis and multifidus combine to
      form the lumbar supraspinous and interspinous ligaments. Their spinal attachments
      produce a system of dense connective tissue with marked regional variation in
      fiber orientation and arrangement. The findings support the description of the
      supraspinous and interspinous ligaments as structures formed by both muscle
      tendons and aponeuroses along the length of the thoracic and lumbar spine, with
      regional differences in their connective tissue architecture.

PMID- 12194002
TI  - Whiplash: a biochemical study of muscle injury.
AB  - Outcome following whiplash injury of the cervical spine is variable, and the
      pathology of those with prolonged symptoms is uncertain. We undertook a
      prospective study in 25 patients to identify whether those with prolonged
      symptoms following whiplash injury exhibit a rise in serum creatine kinase
      consistent with significant muscle damage at the time of injury. Transient rise
      in creatine kinase level was seen in only 2 of 25 patients, neither of whom
      complained of prolonged symptoms. Of the 8 patients who developed chronic
      symptoms following whiplash injury, none demonstrated a serum creatine kinase
      rise. Prolonged symptoms following whiplash injury cannot be explained by
      biochemically measurable muscle damage.

PMID- 12194003
TI  - Effects of meteorological conditions on spore plumes.
AB  - Fungal spores are an ever-present component of the atmosphere, and have long been
      known to trigger asthma and hay fever symptoms in sensitive individuals. The
      atmosphere around Tulsa has been monitored for airborne spores and pollen with
      Burkard spore traps at several sampling stations. This study involved the
      examination of the hourly spore concentrations on days that had average daily
      concentrations near 50,000 spores/m(3) or greater. Hourly concentrations of
      Cladosporium, Alternaria, Epicoccum, Curvularia, Pithomyces, Drechslera, smut
      spores, ascospores, basidiospores, other, and total spores were determined on 4
      days at three sites and then correlated with hourly meteorological data including
      temperature, rainfall, wind speed, dew point, air pressure, and wind direction.
      On each of these days there was a spore plume, a phenomenon in which spore
      concentrations increased dramatically over a very short period of time. Spore
      plumes generally occurred near midday, and concentrations were seen to increase
      from lows around 20,000 total spores/m(3) to highs over 170,000 total spores/m(3)
      in 2 h. Multiple regression analysis of the data indicated that increases in
      temperature, dew point, and air pressure correlated with the increase in spore
      concentrations, but no single weather variable predicted the appearance of a
      spore plume. The proper combination of changes in these meteorological parameters
      that result in a spore plume may be due to the changing weather conditions
      associated with thunderstorms, as on 3 of the 4 days when spore plumes occurred
      there were thunderstorms later that evening. The occurrence of spore plumes may
      have clinical significance, because other studies have shown that sensitization
      to certain spore types can occur during exposure to high spore concentrations.

PMID- 12194004
TI  - Sea-land breeze in a coastal city and its effect on pollen transport.
AB  - This paper presents a statistical study of the sea-land breeze in Mar del Plata
      (Argentina) to characterize the periods of the year when the breeze affects
      pollen transport, particularly the dispersion of airborne Poaceae pollen between
      urban and rural areas. In order to analyse the sea breeze circulation, hourly
      data from coastal, urban and rural meteorological stations were used. The effect
      of the sea breeze on the particulate matter was analysed from syncronic hourly
      airborne pollen records from an urban and a rural area. A sea-land breeze
      appeared between spring and early autumn in the hours of greatest diurnal
      warming. Results showed that the surface wind direction most probably associated
      with this phenomenon is NE and E, the time of occurrence shifting to new
      directions following the counterclockwise rotation, according to theoretical
      models for the Southern Hemisphere. Poaceae emission takes place in the morning,
      during the hours of maximum insolation. However, after the occurrence of the
      breeze, a rise in pollen concentration between 2000 hours and 0200 hours is
      detected because of pollen reentrainment brought about by air recirculation. The
      results showed that breeze transport brings a regional component to pollen
      assemblage.

PMID- 12194005
TI  - Aerial short-range dispersion of volatilized pesticides from an area source.
AB  - Owing to legal provisions, pesticides have to be applied in such a way that there
      is no unacceptable influence on human health and the environment at nearby non
      target areas. In order to quantify their concentration over and downwind of
      agricultural target plots of 0.5-1 ha, covered by winter wheat and winter barely,
      the pesticides lindane, parathion and pirimicarb were applied. Over these plots
      the post-application volatilization rates of the pesticides were estimated
      indirectly from vertical concentration, wind and temperature profile measurements
      using the aerodynamic gradient technique. Philip's advection model was applied to
      take non-favourable fetch conditions into account. In addition, at a height of
      1.6 m downwind of the area source, measurements of the horizontal concentration
      profile were made up to a distance of about 250 m at roughly 50-m intervals. The
      monitoring started immediately after spraying in the morning and continued for
      about 8-10 h, thus providing a worst-case situation because volatilization, and
      therefore pesticide concentration in the atmospheric surface layer, is then
      strongest. The concentration of the airborne pesticides over the downwind non
      target area was also calculated by Philip's advection model. By using the Nash
      Sutcliffe relative-difference measure between observed and calculated
      concentrations, a goodness-of-fit of 0.97 was obtained over the downwind non
      target area, indicating that the Philip model is well suited for dispersion
      estimates in the near-field range.

PMID- 12194006
TI  - Respiratory heat loss in the sheep: a comprehensive model.
AB  - A model is presented for the respiratory heat loss in sheep, considering both the
      sensible heat lost by convection ( C(R)) and the latent heat eliminated by
      evaporation ( E(R)). A practical method is described for the estimation of the
      tidal volume as a function of the respiratory rate. Equations for C(R) and E(R)
      are developed and the relative importance of both heat transfer mechanisms is
      discussed. At air temperatures up to 30 degrees C sheep have the least
      respiratory heat loss at air vapour pressures above 1.6 kPa. At an ambient
      temperature of 40 degrees C respiratory loss of sensible heat can be nil; for
      higher temperatures the transfer by convection is negative and thus heat is
      gained. Convection is a mechanism of minor importance for the respiratory heat
      transfer in sheep at environmental temperatures above 30 degrees C. These
      observations show the importance of respiratory latent heat loss for
      thermoregulation of sheep in hot climates.

PMID- 12194007
TI  - Influence of illumination on autonomic thermoregulation and choice of clothing.
AB  - This study was conducted to investigate how different levels of illumination
      below 1,000 lx would affect the autonomic and behavioral temperature regulation
      of humans. Seven healthy college-aged women (20+/-0 years) volunteered to
      participate in this study. They were exposed to a temperature of 26 degrees C in
      320 lx for 30 min ('Equilibrium') followed by 700 lx or 70 lx for 30 min (stage
      1). After stage 1, they were exposed to 20 degrees C for 30 min in the same
      illumination as in stage 1 (stage 2). In stage 2 the subjects were instructed to
      select and wear the clothing they needed for their thermal comfort. The data
      obtained were analyzed by paired t-test and repeated measures of analysis of
      variance. Forearm skin blood flow tended to remain steady in 700 lx but decreased
      markedly in 70 lx in stage 1. There were no significant differences between
      subjective thermal responses of the subjects experiencing 700 lx or 70 lx in both
      stages although the subjects felt cooler in stage 2 than in stage 1. The subjects
      were likely to prefer wearing heavier clothing in 70 lx than in 700 lx. It was
      concluded that vasoconstriction in the upper limbs occurred more strongly in dim
      light, which might result in different clothing preferences in a cool environment
      from those associated with brighter light intensity.

PMID- 12194008
TI  - Effects of extremely hot days on people older than 65 years in Seville (Spain)
      from 1986 to 1997.
AB  - The effects of heat waves on the population have been described by different
      authors and a consistent relationship between mortality and temperature has been
      found, especially in elderly subjects. The present paper studies this effect in
      Seville, a city in the south of Spain, known for its climate of mild winters and
      hot summers, when the temperature frequently exceeds 40 degrees C. This study
      focuses on the summer months (June to September) for the years from 1986 to 1997.
      The relationships between total daily mortality and different specific causes for
      persons older than 65 and 75 years, of each gender, were analysed. Maximum daily
      temperature and relative humidity at 7.00 a.m. were introduced as environmental
      variables. The possible confounding effect of different atmospheric pollutants,
      particularly ozone, were considered. The methodology employed was time series
      analysis using Box-Jenkins models with exogenous variables. On the basis of
      dispersion diagrams, we defined extremely hot days as those when the maximum
      daily temperature surpassed 41 degrees C. The ARIMA model clearly shows the
      relationship between temperature and mortality. Mortality for all causes
      increased up to 51% above the average in the group over 75 years for each degree
      Celsius beyond 41 degrees C. The effect is more noticeable for cardiovascular
      than for respiratory diseases, and more in women than in men. Among the
      atmospheric pollutants, a relation was found between mortality and concentrations
      of ozone, especially for men older than 75.

PMID- 12194009
TI  - Comparison of the solar spectral ultraviolet irradiance in motor vehicles with
      windows in an open and closed position.
AB  - The solar ultraviolet (UV) spectrum was measured by a spectroradiometer located
      inside two common Australian vehicles: a family wagon and a four-wheel-drive
      vehicle. The entrance optics of the spectroradiometer was orientated, in turn, on
      a horizontal plane, towards the driver and passenger windows and towards the
      windshield. UV spectra were recorded when the vehicles' windows were in an open
      and closed position. For a typical Australian family wagon, on a horizontal plane
      inside the vehicle, closing the windows decreased, the total UV irradiance by a
      factor of 3.2, whilst in a four-wheel drive the irradiance decreased by a factor
      of 2.1. In order to reduce the likelihood of developing of UV-related eye and
      skin disorders, drivers should use appropriate UV protection whilst driving a
      vehicle with the windows in an open position. Results gained from this research
      provide new findings on the exposure of humans to UV in a vehicle.

PMID- 12194010
TI  - TonEBP transcriptional activator in the cellular response to increased
      osmolality.
AB  - TonEBP is a member of the Rel family of transcriptional activators, distinct from
      other members NFkappaB and NFAT. In the medulla of mammalian kidney, TonEBP is a
      local differentiation factor that stimulates the transcription of several genes.
      The activity of TonEBP is regulated by changes in diuretic status mainly at the
      level of nucleocytoplasmic distribution. Some of the genes stimulated by TonEBP
      encode transporters and a synthetic enzyme for cellular accumulation of
      compatible osmolytes, which protect cells from the deleterious effects of
      hypertonicity by lowering cellular ionic strength. Other genes include the
      vasopressin-regulated urea transporters that play a key role in building up high
      urea concentrations in the renal medulla during antidiuresis and a heat shock
      protein 70 that protects cells from the deadly effects of urea. TonEBP is also
      abundantly expressed in other tissues such as brain, heart, liver, and activated
      T-cells. TonEBP plays a significant role in immunity by stimulating several
      cytokine genes in the T-cells. A lot more needs to be learned about the genes
      regulated by TonEBP and signaling pathways from hypertonicity to the activation
      of TonEBP.

PMID- 12194011
TI  - Cyclic AMP has distinct effects from Ca(2+) in evoking priming and
      fusion/exocytosis in parotid amylase secretion.
AB  - Rat parotid acinar cells were perfused in small quartz columns to examine the
      role of cAMP and Ca(2+) in the priming and fusion/exocytosis of amylase
      secretion. Carbachol (CCh) evoked a biphasic response of amylase secretion with
      an initial rapidly occurring large peak and a subsequent sustained plateau.
      Isoproterenol produced slowly increasing amylase secretion that reached the
      plateau greater than that induced by CCh. Combined stimulation with isoproterenol
      and CCh greatly potentiated amylase secretion. The rise and decay of amylase
      secretion induced by the combined stimulation was similar to those induced by CCh
      but not by isoproterenol, suggesting that the potentiation is caused by
      isoproterenol-induced modification of the CCh effect. Concentration-dependent
      responses of CCh-induced amylase secretion with and without isoproterenol showed
      that isoproterenol greatly enhances both the sensitivity and maximum effect of
      CCh. Similar potentiation was observed when the Ca(2+) effect was directly
      examined in cells permeabilized to Ca(2+) with ionomycin instead of CCh. In a
      Ca(2+)-free medium, CCh evoked an initial peak but did not produce a sustained
      plateau. Isoproterenol did not enhance the effect of CCh on [Ca(2+)](i). 2,4
      Dintrophenol and carbonyl cyanide m-chlorophenyl hydrazone did not decrease the
      CCh-induced initial peak of amylase secretion but markedly decreased the
      sustained responses induced by isoproterenol and CCh. These results suggest that
      CCh, via Ca(2+), has two distinct effects on amylase secretion: triggering of
      fusion/exocytosis and the priming of secretory granules. Isoproterenol, via
      cyclic AMP, also has two distinct effects: direct stimulation of priming and
      enhancement of the sensitivity to the Ca(2+)effects. Thus, isoproterenol
      stimulates amylase secretion by increasing the primed pools of secretory
      granules, whereas CCh increases the flux of secretory granules into/from the
      primed pools, which is greatly enhanced by isoproterenol.

PMID- 12194013
TI  - Respiratory responses to ionotropic glutamate receptor antagonists in the ventral
      respiratory group of the rabbit.
AB  - Selective excitatory amino acid receptor antagonists acting on either N-methyl-D
      aspartic acid (NMDA) or non-NMDA receptors were microinjected (30-50 nl)
      bilaterally into different subregions of the ventral respiratory group (VRG) of
      alpha-chloralose-urethane anaesthetized, vagotomized, paralysed and artificially
      ventilated rabbits. Blockade of NMDA receptors by D(-)-2-amino-5
      phosphonopentanoic acid (D-AP5; 1 or 10 mM) within the inspiratory portion of the
      VRG (iVRG) dose-dependently decreased the peak amplitude and rate of rise of
      phrenic nerve activity, without significant changes in respiratory timing.
      Decreases in respiratory frequency and peak phrenic amplitude up to apnoea were
      evoked by 20 mM D-AP5; phrenic nerve activity was restored transiently by hypoxic
      or hypercapnic stimulation during D-AP5-induced apnoea. Microinjections of the
      non-NMDA receptor antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX; 1, 10 or
      20 mM) into the iVRG provoked less intense depressant respiratory effects. No
      significant respiratory responses were evoked by microinjections of these
      antagonists into more caudal VRG subregions. The results suggest that ionotropic
      glutamate receptors within the iVRG are involved mainly in the control of the
      intensity of inspiratory activity, with a major role played by NMDA receptors.
      Glutamate receptor antagonism in the iVRG does not seem to impair the basic
      mechanisms underlying respiratory rhythm generation.

PMID- 12194012
TI  - Functional comparison of HCN isoforms expressed in ventricular and HEK 293 cells.
AB  - Pacemaker current (I(f)) encoded by the HCN gene family contributes importantly
      to cardiac rhythm. That contribution depends on the biophysical characteristics
      of I(f), such as voltage dependence, which vary markedly with cardiac region,
      development and disease. Heterologous expression studies of individual HCN
      isoforms have failed to account for the diverse functionality of the native
      current. To investigate the influence of cellular environment on the gating of
      HCN channels, we compared the functional characteristics of HCN2 and HCN4, the
      two major ventricular isoforms, when over-expressed in a normal context (neonatal
      myocytes) and in a heterologous context (HEK 293 cells). Independent of cell
      type, HCN4 activates substantially slower than HCN2 and with a half-maximum
      activation voltage approximately equal 10 mV less negative. However, both
      isoforms activate more positively in myocytes than in HEK 293 cells. The latter
      result suggests a context dependence (i.e. cell-type specificity) to HCN voltage
      dependence that exerts a comparable influence on these two isoforms. This is
      distinct from the inherent difference in the biophysical properties of HCN2 and
      HCN4.

PMID- 12194014
TI  - Effect of age and cold exposure on morphofunctional characteristics of skeletal
      muscle in neonatal pigs.
AB  - Muscular changes accompanying and/or promoting the rapid postnatal improvement of
      the thermogenic efficiency of shivering were investigated in piglets. Animals
      were obtained at birth or killed after 5 days at thermoneutrality (34-30 degrees
      C) or in the cold (24-15 degrees C), to stimulate intense shivering
      thermogenesis. Fast-twitch-glycolytic (longissimus lumborum) and slow-twitch
      oxidative (rhomboid) muscles were prepared for electron microscopic examination
      and chemical measurements. Muscle-specific changes in energy stores and
      metabolism were observed after birth, including the switch from glycogen to
      lipids and variation of the lactate/pyruvate ratio corresponding to the
      progressive acquisition of the metabolic type of the mature muscles. There was
      major age-related and/or cold-induced development of the structures involved in
      excitation-contraction coupling (triadic profiles, +80% in the cold), oxidative
      metabolism (number of lipid droplets, +81% with age in the cold; number of
      mitochondria, +29% with age or cold; surface of mitochondrial inner membranes,
      +18% with age and +32% in the cold) and contraction potential (myofibril volume,
      +62% with age). In contrast, neither age nor cold affected capillary volume
      density and capillary-to-fibre ratio. The observed changes reflect the immaturity
      and remarkable plasticity of piglet skeletal muscle and are likely to underlie
      its enhanced capacity for shivering thermogenesis after birth.

PMID- 12194015
TI  - Inhibitory effects of PGE(2) on K(+) currents and Ca(2+) oscillations in rat
      pancreatic acinar cells.
AB  - Prostaglandin E(2) (PGE(2)) inhibits pancreatic enzyme secretion and shows a
      protective action against pancreatitis. In this study, we tested the effects of
      PGE(2) on the slowly activating voltage-dependent K(+) channel current ( I(Ks))
      and cholecystokinin (CCK)-induced oscillations of cytosolic [Ca(2+)]
      ([Ca(2+)](i)) in rat pancreatic acini (RPA). I(Ks) in RPA is reportedly augmented
      by both Ca(2+)- and cAMP-mediated secretagogues. PGE(2) (10(-7) M) decreased the
      amplitude of I(Ks), an effect that was more prominent following prior stimulation
      with secretin. The application of the membrane-permeable cAMP analogue 8-Br-cAMP
      prevented the effect of PGE(2) on I(Ks). The Ca(2+)-mediated augmentation of
      I(Ks) by ACh was unaffected by pretreatment with PGE(2). Using fura-2
      fluorescence ratiometry to assess [Ca(2+)](i), CCK (<or=10(-10) M)-induced Ca(2+)
      oscillations were observed in RPAs. The amplitude of the Ca(2+) oscillations was
      decreased by PGE(2), irrespective of the presence of 8-Br-cAMP. RT-PCR analysis
      showed that RPAs express predominantly the EP3 subtype of the PGE(2) receptor and
      its splice variants. Enzyme-immunoassay showed that the secretin-induced
      production of cAMP in RPAs was inhibited by treatment with PGE(2). In summary,
      PGE(2) acts on the EP3 receptors to antagonize the cAMP-generating effect of
      secretin, resulting in the decrease of I(Ks). In addition, PGE(2) suppresses CCK
      induced Ca(2+) oscillations in a cAMP-independent manner. These effects of PGE(2)
      may explain the inhibitory action mechanism of PGE(2) in the exocrine pancreas.

PMID- 12194016
TI  - Vinculin and meta-vinculin in fast and slow rat skeletal muscle before and after
      hindlimb suspension.
AB  - The role of vinculin and meta-vinculin, the major components of costameres, was
      explored by analysing quantitatively the expression of these proteins in a slow
      twitch (soleus) and in a fast-twitch (extensor digitorum longus, EDL) skeletal
      muscle under control conditions and after a reduced functional demand. Meta
      vinculin, previously observed essentially in smooth and cardiac muscle, was also
      present in EDL, in the same amount as vinculin. The soleus contained exclusively
      vinculin, the amount of which exceeded the sum of vinculin and meta-vinculin in
      the EDL. After 3 weeks hypokinesia (hindlimb suspension), the vinculin content of
      the soleus was unchanged but after 6 weeks it had increased by 20% and, moreover,
      there was de novo expression of meta-vinculin. In EDL, the changes in vinculin
      and meta-vinculin after 3 weeks were opposite (+26% and -20% respectively). After
      6 weeks the increase in vinculin was even larger (+33%) while meta-vinculin had
      returned to control levels. The marked expression of meta-vinculin in the
      atrophied soleus suggests a shift in the soleus towards the fast muscle profile
      with respect to cytoskeletal characteristics. On the other hand, the ability of
      slow muscle to maintain posture and to generate force for long periods would
      necessitate cytoskeletal reinforcement.

PMID- 12194017
TI  - Sarcoplasmic reticulum function in slow- and fast-twitch skeletal muscles from
      mdx mice.
AB  - The aim of the present study was to establish whether alterations in sarcoplasmic
      reticulum function are involved in the abnormal Ca(2+) homeostasis of skeletal
      muscle in mice with muscular dystrophy ( mdx). The properties of the sarcoplasmic
      reticulum and contractile proteins of fast- and slow-twitch muscles were
      therefore investigated in chemically skinned fibres isolated from the extensor
      digitorum longus (EDL) and soleus muscles of normal (C57BL/10) and mdx mice at 4
      and 11 weeks of development. Sarcoplasmic reticulum Ca(2+) uptake, estimated by
      the Ca(2+) release following exposure to caffeine, was significantly slower in
      mdx mice, while the maximal Ca(2+) quantity did not differ in either type of
      skeletal muscle at either stage of development. In 4-week-old mice spontaneous
      sarcoplasmic reticulum Ca(2+) leakage was observed in EDL and soleus fibres and
      this was more pronounced in mdx mice. In addition, the maximal Ca(2+)-activated
      tension was smaller in mdx than in normal fibres, while the Ca(2+) sensitivity of
      the contractile apparatus was not significantly different. These results indicate
      that mdx hindlimb muscles are affected differently by the disease process and
      suggest that a reduced ability of the Ca(2+)-ATPase to load Ca(2+) and a leaky
      sarcoplasmic reticulum membrane may be involved in the altered intracellular
      Ca(2+) homeostasis.

PMID- 12194018
TI  - Antisense co-suppression of G(alpha)(q) and G(alpha)(11) demonstrates that both
      isoforms mediate M(3)-receptor-activated Ca(2+) signalling in intact epithelial
      cells.
AB  - We used replication-deficient adenoviruses overexpressing antisense against G(q)
      class alpha-subunits to determine the roles of G(q) and G(11) in mediating M(3)
      receptor-coupled Ca(2+) mobilization in intact HT29 human colonic carcinoma
      epithelial cells. Western blot analysis and confocal microscopy showed that the
      viruses expressing antisense directed against the alpha-subunits of G(q) or G(11)
      produced isoform-specific reductions in the levels of these alpha-subunits. Fura
      2 was used to measure changes in the Ca(2+) response following activation of the
      M(3) receptors by carbachol. The G(alpha)(q) antisense virus suppressed the peak
      Ca(2+) response by 70%, whereas the G(alpha)(11) antisense virus reduced it by
      34%. We then used co-infection with both viruses to determine the effect of
      concomitant suppression of both G(alpha)(q) and G(alpha)(11). Overexpression of
      antisense to both alpha-subunits reduced by approximately 50% the levels of both
      G(alpha)(q) and G(alpha)(11). It also almost completely inhibited the Ca(2+)
      response to carbachol. These data show that both G(q) and G(11) are involved in
      mediating the action of the M(3) receptor on cytosolic Ca(2+) in HT29 cells.
      Furthermore, they suggest that the coupling of the M(3) receptor to these G
      proteins is specific, in that G(alpha)(q) cannot substitute for G(alpha)(11), and
      vice versa.

PMID- 12194019
TI  - Preferential loss of EC coupling gradation at positive membrane potentials in rat
      ventricular myocytes.
AB  - Rat ventricular myocytes switched from a solution containing 1 mM extracellular
      Ca to one containing 5 mM extracellular Ca exhibited larger Ca currents that
      inactivated more rapidly. Their Ca transients exhibited a slower decay. In some
      cells the amplitude of the Ca transients increased markedly, but not in others.
      Strikingly, in about half the cells examined, the graded nature of the Ca
      transients over the range of positive membrane potentials was lost, as were Ca
      transients elicited upon repolarization. These changes were manifest without
      equivalent loss of gradation over the range of negative membrane potentials (-35
      to 0 mV). Such preferential loss of gradation at positive membrane potentials
      also occurred in solutions devoid of extracellular and/or intracellular Na, and
      was abolished by nifedipine. The results suggest that Ca-induced Ca release from
      the SR at positive potentials can saturate or become regenerative if the Ca entry
      trigger is increased. The lack of a similar effect at negative potentials
      indicates that large numbers of activated L-type channels are critical for
      induction of regenerative behavior.

PMID- 12194020
TI  - Detecting synaptic connections in the medial nucleus of the trapezoid body using
      calcium imaging.
AB  - The study of synaptic transmission in brain slices generally entails the patch
      clamping of postsynaptic neurones and stimulation of identified presynaptic axons
      using a remote electrical stimulating electrode. Although patch recording from
      postsynaptic neurones is routine, many presynaptic axons take tortuous turns and
      are severed in the slicing procedure, blocking propagation of the action
      potential to the synaptic terminal and preventing synaptic stimulation. Here we
      demonstrate a method of using calcium imaging to select postsynaptic cells with
      functional synaptic inputs prior to patch-clamp recording. We have used this
      method for exploring transmission in the auditory brainstem at the medial nucleus
      of the trapezoid body neurones, which are innervated by axons from the
      contralateral cochlear nucleus. Brainstem slices were briefly loaded with the
      calcium indicator fura-2 AM and stimulated with an electrode placed on the
      midline. Electrical stimulation caused a rise in intracellular calcium
      concentration in those postsynaptic neurones with active synaptic connections.
      Since <10% of the medial nucleus of the trapezoid body neurones retain viable
      synaptic inputs following the slicing procedure, preselecting those cells with
      active synapses dramatically increased our recording success. This detection
      method will greatly ease the study of synaptic responses in brain areas where
      suprathreshold synaptic inputs occur but connectivity is sparse.

PMID- 12194021
TI  - Na/P(i) cotransporter ( Npt2) gene disruption increases duodenal calcium
      absorption and expression of epithelial calcium channels 1 and 2.
AB  - Mice homozygous for the disrupted type-II Na/P(i) cotransporter gene ( Npt2(-/-))
      exhibit hypophosphataemia, increased serum concentration of 1,25-dihydroxyvitamin
      D (1,25-(OH)(2)D) and calcium (Ca) and elevated urinary Ca excretion. To
      determine whether the hypercalcaemia and hypercalciuria are secondary to 1,25
      (OH)(2)D-stimulated intestinal Ca absorption, we examined the effect of Npt2 gene
      disruption on serum Ca and urinary Ca excretion after an overnight fast, and on
      duodenal Ca absorption. We also compared the duodenal expression of the
      epithelial Ca channels, ECaC1 and ECaC2, and calbindinD(9K) mRNAs, relative to
      that of beta-actin mRNA, in Npt2(+/+) and Npt2(-/-) mice. Both serum Ca and urine
      Ca/creatinine were significantly decreased in Npt2(-/-) mice after an overnight
      fast and were no longer different from that in wild-type mice. Absorption of
      (45)Ca from isolated duodenal segments in vivo and (45)Ca appearing in the plasma
      were significantly increased in Npt2(-/-) compared with Npt2(+/+) mice. In
      addition, the duodenal abundance of ECaC1, ECaC2 and calbindinD(9K) mRNAs was
      significantly elevated in mutant mice relative to that in wild-type mice. In
      contrast, both duodenal Ca absorption and ECaC1 and ECaC2 mRNA abundance were
      lower in mice with X-linked hypophosphataemia ( Hyp) than in normal littermates.
      In summary, we provide evidence for increased duodenal Ca absorption in Npt2(-/-)
      mice and suggest a role for ECaC1, ECaC2 and calbindinD(9K) in mediating this
      response.

PMID- 12194022
TI  - MgATP and phosphoinositides activate Na(+)/Ca(2+) exchange in bovine brain
      vesicles. Comparison with other Na(+)/Ca(2+) exchangers.
AB  - We investigated the metabolic modulation of the Na(+)/Ca(2+) exchanger in
      membrane vesicles obtained from bovine brain. The Na(+)/Ca(2+) exchanger was
      activated by MgATP with a K(0.5) of 336 micro M. Unlike the squid nerve
      Na(+)/Ca(2+) exchanger, this effect required no cytosolic component. Also,
      stimulation is the same in vesicles prepared and/or assayed at the ionic strength
      found in mammals (160 mM) or marine animals (300 mM). Other differences between
      squid and bovine nerve are that the bovine brain Na(+)/Ca(2+) exchanger is not
      stimulated by phosphagens, either phosphoarginine (molluscan source) or
      phosphocreatine (mammalian source); and that stimulation by MgATP in bovine brain
      is related to the production of polyphosphatidylinositides. In this regard bovine
      heart and brain Na(+)/Ca(2+) exchangers behave similarly. These results indicate
      that the mechanisms of metabolic regulation of the squid and mammalian nerve
      Na(+)/Ca(2+) exchangers are not alike and represent differences between species.
      Some differences found between bovine heart and brain exchangers, such as MgATP
      stimulation even at saturating [Ca(2+)] and the smaller degree of activation by
      adenosine 5'- O-(3-thiotriphosphate) (ATP-gamma-S) in the brain, may be related
      to the unequal isoform population in both tissues.

PMID- 12194023
TI  - Production of antibodies and development of highly sensitive formats of enzyme
      immunoassay for saxitoxin analysis.
AB  - In this paper the production of antibodies against saxitoxin (STX) is described,
      as is the optimization and comparison of two competitive ELISA formats (direct
      and indirect) for the detection of this toxin. Tests were performed in a 96-well
      microplate using the toxin-specific polyclonal antibodies produced in our
      laboratory, obtained from rabbits immunized with saxitoxin-keyhole limpet
      hemocyanin (STX-KLH). In indirect ELISA format saxitoxin, conjugated to bovine
      serum albumin (STX-BSA) was coated onto the microtitre plate and incubated with
      standard toxin and anti-STX antibody. A goat anti-rabbit IgG Peroxidase conjugate
      was used to enable detection. In the direct ELISA format, STX standard, STX
      conjugate to horseradish peroxidase (STX-HRP), and enzyme substrate/chromogen
      solution were sequentially added to the microplate after antibody coating.Results
      showed the saxitoxin detection limit to be 3 and 10 pg mL(-1) for direct and
      indirect ELISA formats, respectively. The suitability of the assay for
      quantification of saxitoxin in mussels was also studied. Samples were spiked with
      saxitoxin before and after sample treatment to study the extraction efficiency
      and matrix effect, respectively. After treatment, samples were analysed at 1:1000
      v/v dilution in PBS to minimize the matrix effect and to detect the regulatory
      limit of 40-80 micro g saxitoxin per 100 g mussels as stipulated by the Food and
      Drug Administration. The efficiency of extraction of saxitoxin was from 72 to
      102%. These data were confirmed by liquid chromatography coupled with
      fluorimetric detection, the technique currently used for quantitative
      determination of toxins in seafood.

PMID- 12194024
TI  - Direct competitive ELISA for the determination of polychlorinated biphenyls in
      soil samples.
AB  - A direct competitive ELISA for determination of polychlorinated biphenyls (PCB)
      in soil samples was described. The standard calibration curve based on Delor 103
      (Aroclor 1242) was constructed in the dynamic range of 10-1000 micro g L(-1) and
      a detection limit of 5.0-12.9 micro g L(-1) (or 0.5-1.29 micro g g(-1) soil) was
      achieved. When spiked soil samples were extracted with methanol recoveries were
      90.6-106.3 %. The effect of methanol and DMSO on assay signal and sensitivity was
      established. Eight PCB-contaminated soil samples were analyzed by ELISA and gas
      chromatography (GC). The ELISA results from Soxhlet extraction were in a good
      agreement with those of GC (correlation coefficient 0.9866; n=8). Except for one
      soil sample the results from ELISA with methanol extraction were not
      significantly different from those from GC.

PMID- 12194025
TI  - Flow-injection amperometric determination of pesticides on the basis of their
      inhibition of immobilized acetylcholinesterases of different origin.
AB  - Determination of the organophosphorus pesticides paraoxon, chlorpyrifos oxon, and
      malaoxon has been performed by a method based on inhibition of
      acetylcholinesterase (AChE) and amperometric detection in a flow-injection system
      with enzymes obtained from the electric eel (eeAChE) and Drosophila melanogaster
      (dmAChE) and immobilized on the surface of platinum electrode within a layer of
      poly(vinyl alcohol) bearing styrylpyridinium groups. dmAChE is more sensitive
      than eeAChE to inhibition by chlorpyrifos oxon and paraoxon. The sensitivity
      difference was largest for chlorpyrifos oxon (detection limit approx. 17 times
      lower), and practically none for malaoxon. Determination of the analytes in
      spiked river water samples by use of the dmAChE biosensor resulted in recoveries
      from 50 to 90 % for chlorpyrifos oxon at levels of 20 to 40 nmol L(-1), 50 to 100
      % for paraoxon at 0.6 to 0.8 micro mol L(-1), and 140 to 190 % for malaoxon at
      0.6 to 1.2 micro mol L(-1).

PMID- 12194026
TI  - Pesticide toxicity assessment using an electrochemical biosensor with Pseudomonas
      putida and a bioluminescence inhibition assay with Vibrio fischeri.
AB  - Two different toxicity tests, an electrochemical biosensor Cellsense and a
      bioluminescence inhibition assay ToxAlert were performed in order to establish
      and compare the acute toxicity responses of different types of raw and spiked
      water for a selected group of pesticides. The selected compounds were endosulfan,
      chlorfenvinphos, dimethoate, fenamiphos, ametryn, deltamethrin and alpha
      cypermethrin; all of them are used in large quantities for agricultural purposes.
      In the first step, the study of the toxicity responses for each individual
      pesticide with Milli-Q water was carried out. Next, the toxic responses of
      different mixtures of these pesticides in different water matrices, i.e., Milli-Q
      water, surface water, groundwater and wastewater were studied in order to
      evaluate (i) device advantages and limitations for the toxicity evaluation of
      real environmental samples, (ii) antagonistic or synergistic effects and (iii)
      the influence of the water matrices. The survey of pesticides in real samples was
      carried out using a combined method involving both chemical analysis and toxicity
      bioassays. Chemical analysis involved the use of solid-phase micro-extraction
      (SPME) followed by gas chromatography with electron capture detection (GC/ECD) or
      thermoionic specific detection (GC/TSD) with mass spectrometric confirmation
      (GC/MS).

PMID- 12194027
TI  - Analysis and toxicity of methomyl and ametryn after biodegradation.
AB  - The controlled biodegradation of ametryn and methomyl has been performed, in
      accordance with the OECD Zahn-Wellens/EMPA procedure, by use of an enriched
      mixture of activated sludge collected from three domestic waste-water-treatment
      plants (WWTP). During the process concentrations of ametryn and methomyl in the
      water samples were isolated by solid-phase extraction (SPE); recovery rates were
      98.9 and 93.2 for methomyl and ametryn, respectively. Liquid chromatography-mass
      spectrometry (LC-MS) was used to determine final pesticide concentrations and for
      metabolite identification. The efficiency of aerobic biodegradation of ametryn
      and methomyl was evaluated by measuring both the decrease in the concentration of
      the pesticides and global properties such as the chemical oxygen demand (COD).
      The acute toxicity of ametryn and methomyl was evaluated by use of the
      ToxAlert100 biological test, which is based on inhibition of the bioluminescence
      of Vibrio fischeri. There was significant correlation between results from
      primary and ultimate biodegradation and those from determination of toxicity.
      Pesticide concentrations were always reduced to below the limit of detection in
      less than 17 days. High COD removal (90-96%) was achieved in 28 and 18 days for
      methomyl and ametryn, respectively.

PMID- 12194028
TI  - DNA sensing on glassy carbon electrodes by using hemin as the electrochemical
      hybridization label.
AB  - The electrochemical behavior of hemin, an iron complex of porphyrin, on binding
      to DNA at a glassy carbon electrode (GCE) and in solution, is described. Hemin,
      which interacts with covalently immobilized calf thymus DNA, was detected by use
      of a bare GCE, a double-stranded DNA-modified GCE (dsDNA-modified GCE), and a
      single-stranded DNA-modified GCE (ssDNA-modified GCE), in combination with
      differential pulse voltammetry (DPV). The structural conformation of DNA was
      determined from changes in the voltammetric signals acquired on reduction of
      hemin. As a result of its large steric structure and anionic substitution on its
      porphyrin plane, hemin intercalates between the base pairs of dsDNA. A scan-rate
      study for hemin and the dsDNA-hemin complex were also performed to determine the
      electrochemical behavior of the complex. The partition coefficient was obtained
      from the peak currents measured when different concentrations of hemin were in
      the presence of dsDNA. By observing the oxidation signals of guanine, damage to
      DNA after reaction with hemin at the GCE surface was also detected. The
      electrochemical detection of hybridization between the covalently immobilized
      probe and its target sequence was detected by use of hemin. These results
      demonstrate the use of DNA biosensors in conjunction with hemin for
      electrochemical detection of hybridization and damage to DNA.

PMID- 12194029
TI  - A DNA-electrochemical biosensor for screening environmental damage caused by s
      triazine derivatives.
AB  - An electrochemical DNA-biosensor has been used to investigate the interactions
      between DNA and members of a group of ten derivatives of 1,3,5-triazine
      herbicides: chloro-s-triazines (atrazine, propazine, terbutylazin, and cyanazin),
      thiomethyl-s-triazines (ametryn, prometryn, terbutryn, and simetryn), and methoxy
      s-triazines (prometon and terbumeton). A UV spectrophotometric study of this
      group of herbicides was also undertaken. Of this group only cyanazin could be
      oxidized in aqueous solution using a glassy carbon electrode. Use of the
      electrochemical DNA-biosensor revealed the occurrence of a time-dependent
      interaction of all the herbicides with DNA, via the appearance of guanine,
      guanosine, and adenosine oxidation signals that correspond to DNA damage. Adduct
      formation between the herbicide and the DNA purine bases guanine and adenine is
      suggested as a mechanism.

PMID- 12194030
TI  - Charge mediation by ruthenium poly(pyridine) complexes in 'second-generation'
      glucose biosensors based on carboxymethylated beta-cyclodextrin polymer
      membranes.
AB  - Four different poly(pyridine) complexes of ruthenium, viz.
      Ru(II)(trpy)(phen)(OH(2))](2+) (1), trans-[Ru(III)(2,2'bpy)(2)(OH(2))(OH)](2+)
      (2), [(2,2'bpy)(2)(OH)Ru(III)ORu(III)(OH)(2,2'bpy)(2)](4+) (3), and
      [Ru(II)(4,4'bpy)(NH(3))(5)](2+) (4) (2,2'bpy=2,2'-bipyridine, 4,4'bpy=4,4'
      bipyridine, trpy=2,2',2"-terpyridine, phen=1,10-phenanthroline), were tested as
      non-physiological charge mediators of 'second-generation' glucose biosensors. The
      membranes for these biosensors were prepared by casting anionic carboxymethylated
      beta-cyclodextrin polymer films (beta-CDPA) directly onto the Pt or glassy carbon
      (GC) disk electrodes. Simultaneously, glucose oxidase (GOD) was immobilized in
      the films by covalent bonding and the Ru complexes were incorporated both by
      inclusion in the beta-CD molecular cavities and by ion exchange at the fixed
      carboxymethyl cation-exchange sites. The leakage of the mediator from the polymer
      has been minimized by adopting a suitable pre-treatment procedure. The biosensors
      catalytic activities increased in the order 1<2<3<4, as established by linear
      sweep voltammetry. In case of complexes 2-4, the enzymatic glucose oxidation was
      mediated by the Ru complexes at their redox potentials. However, this oxidation
      was mediated by oxygen in case of complex 1 where H(2)O(2) was detected as the
      reaction product. The effectiveness of the mediators used in the presence of
      oxygen has been estimated using Pt and GC supports. The redox potential of the
      mediator does not depend on the support used, while the oxidation of H(2)O(2)
      proceeds on GC at much higher positive potentials than on Pt. The sensitivity and
      the linear concentration range of the biosensor studied varied significantly. For
      complex 4, which forms stable inclusion complex with beta-CD, the biosensor
      sensitivity was the highest and equal to 7.2 micro A mM(-1) cm(-2), detectability
      was as low as 1 mM, but the linear concentration range was limited only to 4 mM.
      In contrast, for complexes 2 and 3 the sensitivity was 0.4 and 3.2 micro A mM(-1)
      cm(-2), while the linear concentration range extended up to at least 24 and 14 mM
      glucose, respectively. Even though some common interfering substances, such as
      ascorbate, paracetamol or urea, are oxidized at potentials close to those of the
      Ru complex redox couples, their electro-oxidation currents at physiological
      concentrations are insignificant compared to those due to the biocatalytic
      oxidation of glucose. The biosensor response to glucose is reversible as
      demonstrated by the inhibition of GOD activity by Cu(II). That is, the Cu(II)
      concentration required to inhibit by half the response to glucose of the
      biosensor containing complex 2 was 1.0 mM. This inhibitory effect was fully
      reversed by addition of citrate, a ligand forming sufficiently stable complex
      with Cu(II).

PMID- 12194033
TI  - Electrochemical metallization of self-assembled porphyrin monolayers.
AB  - Multifunctional sensor systems are becoming increasingly important in
      electroanalytical chemistry. Together with ongoing miniaturization there is a
      need for micro- and nanopatterning tools for thin electroactive layers (e.g. self
      assembling monolayers). This paper documents a method for production of a micro
      array of different metal-porphyrin monolayers with different sensor properties. A
      new method has been developed for the selective and local metallization of bare
      porphyrin monolayers by cathodic pulsing and sweeping. The metal-porphyrin
      monolayers obtained were characterized by cyclic voltammetry. It was shown that
      porphyrin monolayers can be metallized with manganese, iron, cobalt, and nickel
      by use of the new method. It is expected that all types of metal-porphyrin
      monolayers can be produced in the same manner.

PMID- 12194031
TI  - Properties of glucose biosensors based on dendrimer layers. Effect of enzyme
      immobilization.
AB  - The properties of glucose biosensors based on dendrimer layers on a gold support,
      which depend on the method of immobilization of glucose oxidase (GOX), were
      studied by amperometry. The kinetic parameters of enzymatic reactions, response
      time, sensitivity, detection limit, linear range, and enzyme turnover were
      determined. We showed that a more stable and sensitive sensor was obtained when
      GOX was immobilized on the dendrimer by crosslinking with glutaraldehyde in
      vacuum. This biosensor was stable for at least eight weeks. The response time was
      approximately 1.3 min, the detection limit of glucose was 25 micro M, and the
      apparent Michaelis-Menten constant was relative low ( K(m)=1.1+/-0.1 mM) in
      comparison with that for GOX in solution. The reason for these differences is
      discussed. The example of the application of the developed biosensors for the
      detection of mercury is also presented. The inhibitory effect of mercury on GOX
      activity was observed at mercury concentration of 100 nM.

PMID- 12194034
TI  - Microactuators based on conducting polymers.
AB  - In this contribution we report the use of polyaniline and polypyrrole for
      miniaturized actuators fabricated by microstructural and electrochemical
      technologies. The potential necessary to drive the actuator is typically less
      than 1 V, i.e. 2-3 orders of magnitude lower than that necessary for the
      widespread piezoelectric actuator devices. This low voltage is imperative for
      future application of actuators of micrometer dimensions. The volume variation of
      polymers substantially exceeds that of piezoelectric materials. Different
      contributions to the actuator characteristics are discussed and evaluated semi
      quantitatively.

PMID- 12194035
TI  - Reliable glucose monitoring through the use of microsystem technology.
AB  - A continuous amperometric glucose monitoring system is presented. All
      analytically relevant units are integrated on a microchip (microreactor, control
      electrode, glucose oxidase based sensor electrode, reference electrode, counter
      electrode). The scavenging electrochemical microreactor pre-oxidises all
      interfering compounds enabling a reliable glucose determination. The reliability
      of the microreactor is demonstrated with the most important antioxidants,
      ascorbic and uric acids. The glucose sensor system operates at volumetric flow
      rates of common body interfaces (e.g. microdialysis, microperfusion).

PMID- 12194036
TI  - Potentiometric measurement of cell volume changes and intracellular ion
      concentrations under voltage-clamp conditions in invertebrate nerve cells.
AB  - Because changes in cell volume might disturb the normal function of animal cells,
      most cells are endowed with volume-regulating mechanisms. Experimentally induced
      changes in cell volume are often paralleled by changes in the membrane potential,
      which might affect a variety of transport processes across the cell membrane and,
      in turn, volume regulation [1, 2]. We have shown previously that multi-barrelled
      ion-selective microelectrodes are useful tools for measurement of cell volume and
      the intracellular concentrations of ions that might be relevant to volume
      regulation [1]. To investigate whether voltage-dependent transport processes are
      involved in cell-volume regulation we combined the potentiometric technique of
      ion-selective microelectrodes with the voltage-clamp technique. This combination
      enables simultaneous recording of cell volume, relevant intracellular ion
      concentrations, and ion currents across the cell membrane at a fixed membrane
      potential.

PMID- 12194037
TI  - Speciation of iron coordinated by phytosiderophores by use of HPLC with pulsed
      amperometric detection and AAS.
AB  - Phytosiderophores of the mugineic acid family, and the respective iron species,
      have been separated by anion-exchange chromatography with NaOH gradient elution.
      Two different detection methods were used in parallel, pulsed amperometry (PAD)
      for phytosiderophores and atomic absorption spectrometry (AAS) for iron. This
      combination enables identification of separated iron species. Up to five
      different iron species were separated and detected within 30 min - two different
      phytosiderophore species, two amino acid species, and one species which has not
      yet been identified but which is most probably a decomposition product of
      phytosiderophores. The detection limit was in the low micro mol L(-1)
      concentration range, which is sufficiently low for determination in real plant
      samples, even after dilution. The method has been applied to root washings of
      iron-deficient wheat and barley plants and to a xylem exudate of non-deficient
      maize.

PMID- 12194038
TI  - Trace determination of dexamethasone sodium phosphate in pharmaceutical
      formulations by differential pulse polarography.
AB  - A simple and rapid differential pulse polarographic method has been developed for
      the trace determination of dexamethasone sodium phosphate. A well-defined single
      peak with an Ep value of -1.14 V is obtained in acetate buffer (pH 5.0). The
      linearity is valid in the range 0.2-1.2 mg/25 mL ( r=0.9992) with minimum
      detection limit of 7.6x10(-6) M. The precision of the method developed is implied
      from the values of relative mean deviation, standard deviation and coefficient of
      variation, which are 2.44%, 0.014 and 3.5% respectively. Marketed formulations of
      dexamethasone sodium phosphate have been analysed by calibration and standard
      addition methods. Recovery experiments were found to be quantitative, and
      analysis to determine the mass per tablet was obtained within +/-0.2% of the
      expected market value. The studies have shown that the method is reproducible and
      accurate and can be used in the analysis of marketed formulations.

PMID- 12194039
TI  - Measurement of the kinetics of adsorbed cinnoline by square-wave voltammetry.
AB  - The standard redox reaction rate constant of cinnoline (1,2-benzodiazine)
      adsorbed to the mercury electrode in 0.9 mol L(-1) KNO(3) buffered to pH 7, 9.2,
      and 4.65 are k(s)=455+/-110 s(-1), 65+/-25 s(-1), and 300+/-75 s(-1),
      respectively.

PMID- 12194040
TI  - Cross contamination of lead and cadmium during dry ashing of food samples.
AB  - Common white sugar was ashed in a muffle furnace under controlled heating at 450
      degrees C. Together with these samples, sugar with added amounts of Pb and Cd
      (20, 50 micro g) was mineralized in the same furnace. Depending on the absolute
      amount of Pb and Cd present in the furnace, an increase in the 'blank' values of
      the unspiked sugar samples was found. The same effect was observed when reference
      material containing natural amounts of Pb and Cd (TORT-1, Lobster) was present in
      the furnace. Although the results strongly depend on the blank levels of the
      muffle furnace, cross contamination effects could be demonstrated for both
      elements. The investigations demonstrate, that at a temperature of 450 degrees C,
      both Cd and Pb are lost during ashing of samples. The type of matrix in a sample
      with high contents of Pb and Cd has no significant effect on the volatility of
      these elements. The vapor lost from a sample containing high amounts of Pb and Cd
      will falsify the concentration in low level samples present in the furnace.

PMID- 12194041
TI  - Automatic decoding of sensor types within randomly ordered, high-density optical
      sensor arrays.
AB  - In this paper automatic sensor identification of sensor classes within a high
      density randomized array, without a priori knowledge of sensor locations, is
      demonstrated. Two different fluorescence-based sensor types, with hundreds of
      replicates each, were randomly distributed into an optical imaging fiber array
      platform. The sensor element types were vapor-sensitive microspheres with the
      environmentally-sensitive fluorescent dye Nile Red adsorbed on their surface.
      Nile Red undergoes spectral changes when exposed to different microenvironmental
      polarity conditions, e.g. microsphere surface polarity or odor exposure. These
      reproducible sensor spectral changes, or sensor-response profiles, enable sensors
      within a randomized array to be grouped into categories by optical decoding
      methods. Two computational decoding methods (supervised and unsupervised) are
      introduced; equal classification rates were achieved for both. By comparing
      sensor responses from a randomized array with those obtained from known (control)
      arrays, 587 sensors were correctly classified with 99.32% accuracy. Although both
      methods were equally effective, the unsupervised method, which uses sensor
      response changes to odor exposure, is a better decoding model for the vapor
      sensitive arrays studied, because it relies only on the odor-response profiles.
      Another decoding technique employed the emission spectra of the sensors and is
      more applicable to other types of multiplexed fluorescence-based arrays and
      assays. The sensor-decoding techniques are compared to demonstrate that sensors
      within high-density optical chemosensor arrays can be positionally-registered, or
      decoded, with no additional overhead in time or expense other than collecting the
      sensor-response profiles.

PMID- 12194042
TI  - A piezoelectric immunoassay based on self-assembled monolayers of cystamine and
      polystyrene sulfonate for determination of Schistosoma japonicum antibodies.
AB  - A piezoelectric immunosensor based on an improved immobilization strategy
      combining self-assembled monolayers (SAM) of cystamine (Cys) and polystyrene
      sulfonate (PSS) has been developed for the determination of Schistosoma japonicum
      antibodies (SjAb) in rabbit serum. Cys SAM were first applied to the gold
      electrode surface of the crystal, serving as a positively-charged base.
      Schistosoma japonicum antigen (SjAg) was then electrostatically immobilized on
      the crystal by means of a negatively-charged PSS layer. When sealed by use of an
      appropriately selected blocking reagent for BSA and normal rabbit serum (NRS),
      non-specific adsorption could be substantially reduced. The immunosensor was used
      to determine SjAb in optimized buffer medium with addition of poly(ethylene
      glycol) (PEG), which served as an immunoreaction enhancer. It was shown
      experimentally that SjAg immobilized by the Cys-PSS adsorption procedure had
      higher immunological activity or binding efficiency than those immobilized by the
      glutaraldehyde (GLU) binding or direct attachment procedures. The immunosensor
      developed had satisfactory sensitivity and detection limit, and regeneration of
      the piezoelectric quartz-crystal was easy. Analytical results obtained with
      infected rabbit serum samples indicated that the proposed immunosensor is a
      promising alternative for qualitative and quantitative determination of SjAb in
      clinical diagnosis of infection with Schistosoma japonicum.

PMID- 12194043
TI  - Development of an HPLC-NMR method for the determination of PAHs in soil samples -
      a comparison with conventional methods.
AB  - A hyphenated HPLC-(1)H NMR method for the identification and quantification of
      PAHs in soil samples has been developed and applied to a PAH reference sample
      provided by the Federal Institute for Materials Research and Testing (BAM,
      Berlin, Germany). The results were compared with those obtained by HPLC-DAD, HPLC
      F, and GC-MS analyses of the same sample.

PMID- 12194044
TI  - Determination of gallium in soil by slurry-sampling graphite-furnace atomic
      absorption spectrometry.
AB  - A graphite-furnace atomic-absorption spectrometric method, utilizing ultrasonic
      slurry-sampling has been developed for the determination of Ga in soils.
      Calibration with aqueous standards and with slurries prepared from a certified
      soil reference material were both employed. When calibration with soil slurries
      was used no modifier was needed. Because lower and more variable sensitivity was
      obtained for Ga in aqueous standards than for Ga in slurry soil samples, external
      calibration with aqueous Ga standards required a suitable chemical modifier to
      level out the sensitivity difference. Of the many potential modifiers tested,
      i.e. Al, As, Co, Mg, Mo, Ni, Pd, Pd+Mg, Se, and Te, Ni was found to be best. When
      Ni (1.0 mg mL(-1), 10 micro L) was injected to the graphite tube with the aqueous
      standards or slurry samples (10 micro L) accurate results were obtained. Both
      methods of calibration gave acceptable accuracy and precision. The repeatability
      was <or=4.6% (RSD) for slurry sampling for both methods of calibration. The
      intermediate precision for analyses performed on three different days was 7.3%
      and 4.8% when using aqueous standards and slurry standards, respectively. The
      limit of detection for Ga was 3.0 micro g L(-1)in soil slurry solution,
      equivalent to 0.08 micro g g(-1) in the soil samples. Results from slurry
      sampling were compared with results from microwave-digested samples. Chemical
      interference was observed when the acid-mixture used to dissolve the samples
      contained HF. This interference was eliminated when Ni was added as chemical
      modifier. The repeatability was <or=7.2% (RSD) for analysis of decomposed
      samples.

PMID- 12194045
TI  - Effects of cadmium on cation concentrations in sycamore cells (Acer
      pseudoplatanus L.): application of EDXRF.
AB  - Knowledge of the element content of biological systems is important in enabling
      understanding of uptake mechanisms and physiological response to stress
      conditions. In this work concentrations of mineral elements in sycamore (Acer
      pseudoplatanus L.) cells grown in the presence of cadmium have been analysed and
      compared with concentrations in control cells. Energy-dispersive X-ray
      fluorescence (EDXRF) was used to quantify the nutrients K, Ca, Mn, Fe, Cu, and Zn
      present in the cells. The reproducibility and accuracy of the technique were
      demonstrated by analysis of biological reference materials. Exposure of sycamore
      cells to cadmium had induced variation in the content of some elements. Mn, Cu,
      Zn, and, particularly, Fe concentrations in cells exposed to Cd were higher than
      those found in control cells. Ca is adsorbed on the cell walls and the
      concentration of K is not affected by the presence of Cd.

PMID- 12194046
TI  - Characterization and comparison of two ligno-cellulosic substrates by (13)C
      CP/MAS NMR, XPS, conventional pyrolysis and thermochemolysis.
AB  - Ligno-cellulosic substrates (LCSs) isolated from wheat straw and bran exhibit
      high complexing capacities and may have important applications for metal removal
      from industrial effluents. These two LCSs were examined in the present work by
      spectroscopic and pyrolytic methods (solid state cross polarization magic angle
      spinning (CP/MAS) (13)C NMR, XPS, conventional Curie pyrolysis (Cupy)/GC/MS, and
      TMAH thermochemolysis/GC/MS). This combined study highlighted the limitation of
      some of the above methods when applied to ligno-cellulosic materials and the
      resulting biases and the usefulness of TMAH thermochemolysis. A large difference
      in composition was observed between bran- and straw-LCS due to a much higher
      contribution of alkyl moieties in the former. These moieties correspond to fatty
      acids esterified to the ligno-cellulosic macromolecular structure and such
      carboxylic functions should play an important role for metal complexation.

PMID- 12194047
TI  - Determination of tobacco alkaloids by gas chromatography with nitrogen-phosphorus
      detection.
AB  - An improved method, gas chromatography (GC) with nitrogen-phosphorus detection
      (NPD), has been used for determination of alkaloids in green and cured tobacco.
      Tobacco alkaloids of interest included nicotine, nornicotine, myosmine,
      anabasine, and anatabine. Tobacco samples were treated with a small quantity of
      aqueous ammonia solution to "loosen" tobacco tissue and to adjust pH, then
      extracted with solvent. The composition of the extraction solvent solution
      affected recoveries of the alkaloids, particularly nornicotine, and also
      contributed to other phenomena such as carry-over in the injection liner and
      "quenching" of the nitrogen-phosphorus detector. Use of a packed injection liner
      (e.g. with Carbowax-KOH on Chromosorb) to reduce carry-over was studied.
      Quenching of the nitrogen-phosphorus detector was eliminated by reducing the
      injection volume (i.e. increasing the split ratio), by use of a packed injection
      liner, and by reducing the amount of pretreatment with aqueous ammonia. A narrow
      bore capillary column (i.e. 0.18 mm id) was used to improve sensitivity and
      resolution and to increase the speed of GC analysis. An internal standard, 2,4'
      dipyridyl, was used for quantitative measurement of these tobacco alkaloids.

PMID- 12194048
TI  - A simple and very sensitive spectrophotometric method for the direct
      determination of copper ions.
AB  - A sensitive spectrophotometric method for the direct determination of copper in
      aqueous samples without a preconcentration step has been developed. It is based
      on the formation of a yellow complex with the chromogenic reagent di-2-pyridyl
      ketone benzoylhydrazone (dPKBH) in an alkaline medium. The complex stoichiometry
      was 1:2 (Cu:dPKBH) and presents maximum absorbance at 370 nm. The influence of
      chemical variables affecting the behaviour of the system such as pH,
      concentration of dPKBH, buffer solution and ethanol, order of addition of the
      reagents and stability of the complex, were evaluated. The molar absorptivity
      (epsilon) was 3.92x10(4) L mol(-1) cm(-1), and Beer's law was obeyed up to 3 mg
      L(-1) of copper. The relative standard deviation was 0.46% (n=11) for a sample
      containing 1 mg L(-1) Cu(II). The limit of detection was 2.5 micro g L(-1) and
      was therefore more sensitive than the direct methods reported previously.
      Finally, the method was successfully validated by analysing several real samples
      with different matrices, such as tap water, natural water or copper alloys, with
      an average relative error of 2.46%.

PMID- 12194049
TI  - Comparison of chloride- and hydride-generation for quantitation of germanium by
      headspace solid-phase microextraction-inductively coupled plasma-mass
      spectrometry.
AB  - Chloride- and hydride-generation headspace solid-phase microextraction (SPME)
      techniques have been compared for the detection of trace amounts of germanium by
      inductively coupled plasma time-of-flight mass spectrometry (ICP-TOFMS). The
      conditions for generation of germanium chloride, including acid type and
      concentration, effect of sodium chloride and extraction time, were investigated.
      Detection limits of 20 and 92 pg mL(-1) and precisions of 18% (n=11) and 9.7%
      (n=11) were achieved for chloride and hydride generation, respectively, at a
      concentration of 10 ng mL(-1). The generated germanium chloride and hydride
      species identities were characterized and confirmed as GeCl(4) and GeH(4) by use
      of electron-impact ionization mass spectrometry. Chloride generation coupled with
      SPME sampling and ICP-TOFMS detection resulted in twofold enhancement of
      sensitivity compared to GeH(4)and detection limits for continuous hydride
      generation were 20-fold better than reported atomic fluorescence data.

PMID- 12194050
TI  - Use of dicyclohexano-18-crown-6 to separate traces of silver(I) from potassium
      thiocyanate in hydrochloric acid media, and determination of the silver by atomic
      absorption spectrometry.
AB  - Solvent extraction with 0.05 mol L(-1) dicyclohexano-18-crown-6 (DC18C6) in 1,2
      dichloroethane, coupled with flame atomic absorption spectrometry (AAS), has been
      investigated as a new method for separation of trace amounts of silver(I) from
      0.05 mol L(-1) potassium thiocyanate in 1.0 mol L(-1) hydrochloric acid media and
      quantification of the amount of silver present. The method is based on the
      formation of an extractable ion-association product, [DC18C6.K](+)[Ag(SCN)(2)](
      ), with a metal-to-crown ether ratio of 1:1 (as derived from slope analysis
      data). Stripping of the extracted silver(I) in the 1,2-dichloroethane phase was
      achieved within 5 min by use of 3.0 mol L(-1) potassium thiocyanate. Reducing the
      concentration of acid in the sample solution to 0.1 mol L(-1) improved the
      preconcentration factor severalfold. Excellent tolerance of the proposed method
      to the presence of foreign ions in solution with silver(I) was demonstrated. A
      detection limit of 13 ng mL(-1) was derived from the mean value of the blank plus
      three times its standard deviation. The method was used to determine traces of
      silver(I) after separation from gold(III), platinum(IV), and palladium(II)
      matrices on the basis of extractability differences with 18-membered crown ethers
      under specified conditions. The efficiency of the adopted ion-association
      mechanism for silver(I) extraction was apparent from the average recovery of 96%
      for spiked standards by use of the back-washing technique. The proposed
      extraction procedure was applied to the determination of traces of silver(I) in a
      selection of chemical reagents.

PMID- 12194051
TI  - Application of sequential extraction with supercritical CO(2), subcritical H(2)O,
      and an H(2)O/CO(2) mixture for estimation of environmentally mobile heavy metal
      fractions in sediments.
AB  - Results from use of a new isolation procedure based on sequential extraction with
      supercritical CO(2), subcritical H(2)O, and an H(2)O/CO(2) mixture in the same
      supercritical fluid extractor have been compared with results from the BCR
      recommended three-step sequential extraction procedure. The new procedure gives
      more detailed information about environmentally mobile fractions (water-soluble,
      bicarbonate-forming), and in less time (5-6 h), than the BCR procedure.

PMID- 12194052
TI  - Quinoline-8-ol-immobilized Amberlite XAD-4: synthesis, characterization, and
      uranyl ion uptake properties suitable for analytical applications.
AB  - Amberlite XAD-4 has been functionalized by coupling it with 5-aminoquinoline-8-ol
      after acetylation. The resulting resin has been characterized by elemental
      analysis and IR spectra and has been used for preconcentrating uranyl ions prior
      to its determination by spectrophotometry. The optimum pH value for quantitative
      sorption is 4-6, and desorption can be achieved by using 5 mL of 1 mol L(-1) HCl.
      The sorption capacity of the resin is 11.5 mmol g(-1). The effect of various
      cations and anions on the preconcentration of uranium in conjunction with the
      determination procedure has been studied and we have found that none of the ions
      interfere except thorium. The enrichment factor for preconcentration of uranium
      was found to be 200. Ten replicate determinations of 40 micro g of uranium
      present in 1 L of sample gave a mean absorbance of 0.185 with a relative standard
      deviation of 2.64%. The detection limit corresponding to three times the standard
      deviation of the bank was found to be 2 micro g L(-1). The validation of the
      developed preconcentration procedure was carried out by successfully analyzing
      standard marine sediment reference material. The uranyl content of sediment and
      soils is estimated by spectrophotometry after its preconcentration with the above
      chelating resin.

PMID- 12194053
TI  - Determination of chromium speciation in natural systems using DGT.
AB  - The techniques of diffusive gradients (DGT) and equilibration (DET) in thin-films
      have been combined in a single probe that can determine Cr(III) and Cr(VI)
      simultaneously in solution. The assembly has a layer of polyacrylamide hydrogel
      overlying a separate layer of resin embedded in gel. Cr(III) species accumulate
      exclusively and quantitatively in the resin layer, while Cr(VI) species
      equilibrate with both hydrogel and resin layers. The species are separated by
      peeling the two layers apart. Chromium is then eluted from each of the two
      layers. Cr(III) and Cr(VI) were determined quantitatively in standard, mixed
      solutions by in situ separation with DGT and detection by GF-AAS. With this
      method, Cr(III) is typically preconcentrated by a factor of 10 over a 24 h
      deployment, and limits of detection of 8 ng/L Cr(III) and 0.3 micro g/L Cr(VI)
      were achieved. Due to the inbuilt preconcentration of Cr(III), the technique is
      particularly good at measuring low concentrations of Cr(III) in the presence of
      an excess of Cr(VI). Measurements were performed in three soils with various
      levels of chromium contamination. A concentration of 3 micro g/L of labile
      Cr(III) was measured reproducibly in the presence of 290 micro g/L of unreactive
      Cr species and 0.2 micro g/L of labile Cr(III) was measured in the presence of 24
      micro g/L of unreactive Cr. The unique feature of the method is that the
      separation of Cr(III) from Cr(VI) occurs in situ. The Cr species are then stable
      in the resin and gel prior to analysis, eliminating the artefacts associated with
      sampling and storage, which are particularly prevalent for redox-sensitive
      elements. Therefore, it has great potential for assessing Cr(III) and Cr(VI)
      concentrations in situ in environments near redox boundaries where possible
      dynamic changes in Cr(III) and Cr(VI) concentrations are occurring.

PMID- 12194054
TI  - Speciation of nitrogen - [N(3-)] and [N(2)(2-)] - in binary compounds.
AB  - The nitrogen content of the binary compounds SrN = Sr(4)[N](2)[N(2)], Sr[N(2)],
      and Ba[N(2)] (prepared by high-pressure syntheses) was determined analytically by
      using the carrier gas hot extraction method. For handling of the air- and
      moisture-sensitive samples, a transfer chamber was constructed to protect the
      compounds against decomposition before being analyzed. Additionally, it was
      necessary to develop a method allowing controlled and variable heating of the
      electrode furnace to get analytical results with high precision and accuracy. By
      means of a suitable temperature program it was possible not only to verify the
      existence but also to quantify the two different nitrogen species ([N(3-)] and
      [N(2)(2-)]), and thus confirm the results of recent neutron diffraction studies.

PMID- 12194057
TI  - Application of XRF, XRD, thermal analysis, and voltammetric techniques to the
      study of ancient ceramics.
AB  - An in-depth chemical-analytical study has been performed on biscuit and mortar
      from 17th-18th century tiles from a mediaeval hermitage in the province of
      Valencia (Spain). Representative samples were chosen from the tile fragments
      available, using appearance, essentially color and consistency, as the criterion.
      The chemical composition was analyzed by X-ray fluorescence of the samples in the
      form of glass disks after a previous qualitative study to choose the standard
      materials for calibration and the experimental conditions used in the analysis. X
      ray diffraction of the samples provided information about the mineralogical
      composition which was consistent with the firing of the original materials; it
      also gave information about the range of temperatures used in the firing. From
      thermal gravimetric analysis of the limestone, and from historical
      considerations, it was possible to deduce the raw materials used and their
      approximate composition in the tiles. In the same way it was possible to
      determine the nature of the mortars used to fix the tiles. Cyclic voltammetric
      study of the iron(II) and iron(III) system in the biscuit showed the simultaneous
      presence of both oxidation states, corroborating the results.

PMID- 12194056
TI  - Quantitative structure-retention relationships of xanthines in RP HPLC systems
      with the new Chromolith RP-18e stationary phases.
AB  - The structural descriptors with the best potential for predicting the reversed
      phase retention of xanthines and their derivatives on the new Chromolith RP-18e
      columns have been examined, as has the molecular mechanism of the separation.
      QSRR analysis was performed by simultaneous solution of a set of linear
      equations. The logarithms of the capacity factors were the dependent variables.
      Structural descriptors calculated by means of semi-empirical methods of quantum
      chemistry were chosen as independent variables.

PMID- 12194055
TI  - Application of artificial neural networks in multivariable optimization of an on
      line microwave FIA system for catalytic kinetic determination of iridium(III).
AB  - A new rapid, selective and sensitive on-line microwave flow injection-kinetic
      method was developed for spectrophotometric determination of micro amounts of
      Ir(III), based on its catalytic effect on the m-acetylchlorophosphonazo (CPA-mA)
      and KIO(4) reaction in NaOH media. An on-line microwave oven was employed to
      accelerate the reaction. The reaction was followed spectrophotometrically by
      measuring the decrease of the absorbance of CPA-mA at 580 nm. The effect of five
      variables for the determination of Ir(III) was optimized by means of a multilayer
      artificial neural network using extended delta-bar-delta (EDBD) algorithms. Under
      the optimum experimental conditions, Ir(III) could be determined in the range
      0.060-0.60 micro gZZZ;mL(-1) with detection limit of 0.02 micro gZZZ;mL(-1) and
      the sampling frequency of 34 h(-1). The proposed method was applied to the
      determination of micro amounts of Ir(III) in refined ore and secondary alloy with
      the recoveries from 91.4% to 109%.

PMID- 12194058
TI  - The assessment of management of strabismus and amblyopia and national audit by
      Wickham.

PMID- 12194059
TI  - Clinical, radiological and pathological examination of periocular dermoid cysts:
      evidence of inflammation from an early age.
AB  - INTRODUCTION: Periocular dermoid cysts are common and leakage of the lipid or
      keratin contents leads to an inflammation-often asymptomatic-around the cyst,
      which may cause adherence of the dermoid cyst to neighbouring structures.
      PURPOSE: To investigate the frequency of clinical and radiological signs of
      inflammation with periocular dermoid cysts, to relate this to the
      histopathological examination of the excised specimens, and to assess whether the
      degree of inflammation is related to age at presentation. PATIENTS AND METHODS: A
      retrospective non-comparative series of 124 patients with periocular dermoid
      cysts that had undergone imaging. Case-notes were reviewed for clinical and
      histopathological details and there was independent review of the radiological
      imaging. RESULTS: Surgery was undertaken at between 1 and 66 years of age, most
      patients being under 10 years, and the duration of symptoms varied from 4 weeks
      to 30 years. Symptoms of inflammation-mainly intermittent lid swelling with
      localised redness and pain-occurred in all age groups, the proportion being
      greatest in the fourth decade. Clinical signs of inflammation at the time of
      clinic visit were relatively few, although 8% had some localised erythema and 7%
      had tenderness at the site of lesion. In more than two-thirds of the excised
      cysts, pathological examination demonstrated various degrees of chronic
      inflammation, even in those cysts removed before the age of 5 years. CONCLUSION:
      Even if the patient does not have symptoms or signs of inflammation, most
      periocular dermoid cysts show histological evidence of inflammation due to
      leakage of the lipid and keratin contents from the cyst, the incidence being
      similar at all ages.

PMID- 12194060
TI  - Triple cycle audit of primary retinal detachment surgery.
AB  - PURPOSE: To determine the effect of increasing subspecialisation on the results
      of retinal detachment surgery in one city. METHODS: Three audit cycles over a 10
      year period when major subspecialisation and organisational changes were
      occurring. Retrospective case note reviews of all primary surgery for
      rhegmatogenous retinal detachments in each of the audit periods. Statistical
      analyses used contingency table/chi-square methods for comparing all three audits
      and Fisher's exact test/mean odds ratio with 95% confidence intervals (CIs) for
      the Audit 1 vs Audit 3 comparison. RESULTS: A marked improvement in success rates
      occurred: primary reattachment rose from 67% in Audit 1 to 87% in Audit 3 (P =
      0.0004), and final success from 84% to 97% (P = 0.0003). There was a dramatic
      change in operative techniques over the same period: the percentage of
      vitrectomies increased from 1.5% in Audit 1 to 48% in Audit 3, while that of
      'open' conventional procedures decreased from 78% to 32%. However, the
      improvement in anatomical success was not mirrored by an increase in the
      percentage of patients with 6/12 or better visual acuity postoperatively (55% in
      Audit 1, 49% in Audit 3; P = 0.34, mean odds ratio = 0.78; 95% CI 0.48-1.2). The
      percentage of patients with 6/18-6/36 post op visual acuity did increase in Audit
      3 (18% in Audit 1; 29% in Audit 3; P = 0.03, mean odds ratio = 1.9; CI 1.1-3.3),
      and the percentage with 6/60 or worse decreased (27% in Audit 1, 20% in Audit 3;
      P = 0.26, mean odds ratio = 0.71; CI 0.40-1.2). CONCLUSIONS: With increased
      subspecialisation there has been an increase in anatomical success, but the goal
      of 100% reattachment is still not being attained. There remains scope for further
      improvement in anatomical and functional outcomes.

PMID- 12194061
TI  - A study of heredity as a risk factor in strabismus.
AB  - AIMS: Inheritance is recognised to have a part in the aetiology of strabismus but
      previous studies have not adequately distinguished between different types of
      strabismus leading to wide variations in reported findings. The aim of this study
      was to investigate the importance of heredity in different types of strabismus.
      METHODS: The parents of children attending for treatment of strabismus over a one
      month period were interviewed to identify relatives with a history of strabismus.
      A complete three-generation pedigree was established for 96 index cases who were
      classified into four groups: infantile esotropia (26 cases), accommodative
      esotropia (49 cases), anisometropic esotropia (15 cases), and exotropia (six
      cases). RESULTS: Forty-three of a total of 165 (26.1%) first degree relatives of
      patients with hypermetropic accommodative esotropia were affected. In contrast,
      15 of a total of 101 (14.9%) first degree relatives of patients with infantile
      esotropia, eight of a total of 66 (12.1%) first degree relatives of patients with
      anisometropic esotropia, and one of a total of 25 (4%) first degree relatives of
      patients with exotropia were affected. Analysing the data using logistic
      regression with a random term for family showed a significantly higher proportion
      of affected first degree relatives in the accommodative group than in any of the
      other three diagnostic groups. CONCLUSION: A history of strabismus appears to be
      more common in hypermetropic accommodative esotropia than in infantile esotropia,
      anisometropic esotropia or exotropia. More detailed investigation of the role of
      heredity in the aetiology of accommodative esotropia is needed.

PMID- 12194062
TI  - The assessment and management of strabismus and amblyopia: a national audit.
AB  - AIMS: To determine what systems are in place within ophthalmic services for the
      assessment and management of children suspected of having amblyopia and
      strabismus. To find out what methods are used for the assessment of these
      children. METHODS: A questionnaire-based study auditing 288 orthoptic departments
      in the UK. RESULTS: Responses were received from 75% orthoptic departments. Most
      hospitals employ more than one system for the assessment of strabismus and
      amblyopia, which is generally dependent on route of referral. These include
      'orthoptic assessment without refraction' (66%), 'combined orthoptist and
      ophthalmologist assessment' (66%), while 22% have an entirely
      orthoptist/optometric system. Ophthalmologists are involved in the initial
      assessment in 145 units (67%), whereas some units involve an ophthalmologist only
      if response to treatment is poor (15%), or if surgery is required (6%). Fourteen
      per cent of units reviewed all children, with discharge criteria being based on
      normal visual acuity (52%), accurate visual acuity (39%) and a normal orthoptic
      assessment (42%). Seventy-six per cent of units review some children, commonly as
      a result of family history (55%), parental concern (43%), poor co-operation (30%)
      and young age (72%). In the absence of squint or amblyopia children are
      discharged at the first visit, in only 8% of units. There is considerable
      variation in the tests used to assess visual acuity. LogMAR-based tests (eg
      EDTRS) are not routinely used in 75% of units. CONCLUSION: Different systems
      exist for the assessment and management of squint and amblyopia across the
      country. While much of this variation is to be expected given their possible
      aetiologies, some could be reduced to produce a more cohesive service. There is
      also considerable scope for rationalising the tests used to screen infants and
      children for amblyopia and strabismus.

PMID- 12194063
TI  - Survey of school children with visual impairment in Bradford.
AB  - This work was presented as a poster at the Institute of Health Research
      Conference 2000: Health of Children and Young People: Research Perspectives.
      University of Bradford 15th of September 2000. AIMS: The aim of this survey was
      to determine the prevalence and aetiology of visual impairment in school children
      in Bradford. METHODS: The case notes of school children with predominantly
      uncomplicated visual impairment were reviewed. Data including age, sex, race and
      information on visual diagnosis, heredity, degree of visual impairment and
      additional morbidity were collected. RESULTS: Seventy-two children between the
      ages of 5 and 16 years were included in this survey. The male: female ratio was
      2.1: 1. Twenty-one children were Caucasian, 42 were of Pakistani and nine of
      other racial origin. The most common diagnoses were congenital nystagmus (19),
      ocular albinism (6), myopia (4), cataract (4) and microphthalmia (4). Twenty-five
      children had a genetically linked visual diagnosis and 31 had a family history of
      the same visual disorder. CONCLUSIONS: This survey showed similar causes of
      visual impairment as described in other studies on children with uncomplicated
      visual impairment and confirmed the previously described preponderance of boys.
      The proportion of Pakistani children in our study population was significantly
      higher than that in the general Bradford population, indicating a higher
      prevalence of visual impairment in this group. Children of Pakistani origin were
      significantly more likely to have genetically linked visual disease and a
      positive family history of the same visual disorder than children of Caucasian
      origin. This is probably due to genetic factors and a higher proportion of
      consanguineous marriages in this population. Information about the prevalence and
      causes of visual impairment is important for adequate provision of special
      services and for developing preventive strategies.

PMID- 12194064
TI  - Surgical blepharoptosis--the bridle suture factor?
AB  - AIMS: To evaluate the role of the superior rectus bridle suture in the
      development of post cataract blepharoptosis. METHODS: We compared the incidence
      of postoperative ptosis in two groups of patients undergoing cataract extraction.
      In the first group (32 patients), a temporal corneal approach was employed with
      no superior rectus bridle suture. In the second group (38 patients), a superior
      approach with a bridle suture was used. Both groups of patients underwent
      phacoemulsification with the use of peribulbar anaesthesia, a pressure lowering
      device and a speculum. We recorded the lid position at least 12 weeks following
      surgery and determined the degree of postoperative ptosis. Two-sided Fischer's
      Exact Test was used to test for significant difference between the two groups
      (using a statistical software package Instat Version 3.0 for Windows). RESULTS:
      Taking 2 mm of ptosis as a significant change, 11.5% of those undergoing temporal
      section sustained postoperative ptosis whilst it occurred in 12.9% of those who
      underwent a superior approach. CONCLUSIONS: The presence or absence of the
      superior rectus bridle suture and the site of the ocular wound do not
      significantly contribute to the incidence of postoperative ptosis. We would
      suggest that the causative factors are peribulbar anaesthesia, a pressure
      lowering device and the use of the speculum.

PMID- 12194065
TI  - Retinopathy of prematurity: are we screening too many babies?
AB  - PURPOSE: With advancement in neonatal care units, early detection of retinopathy
      of prematurity (ROP) in premature and very-low-birth-weight infants is important.
      Numerous studies have reported an increased risk of ROP in prematurely born
      infants, but only few have been long-term and strictly population-based. The aim
      of the present study was to find out whether birthweight <1251 grams and
      gestational age <30 weeks could provide a safe and efficient means of detecting
      treatable ROP. We have retrospectively tried to ascertain the incidence and
      associated risk factors that may contribute to the management of babies with ROP.
      METHODS: Infants either with a birth weight below 1500 g or a gestational age of
      less than 32 weeks were screened for ROP during an 8-year period by a single
      examiner. Results An incidence of 64/205 (31.2%) ROP was noted. The mean age at
      detection was 5.5 +/- 2 weeks of life. The maximum stage reached was stage 1 in
      27 (13.2%), stage 2 in 24 (11.7%) and stage 3 in 10 (4.8%) babies. Threshold ROP
      was present in three (1.5%) babies. Significantly fewer (150/205 = 73%) babies
      would have been examined had a birth weight of <1251 grams and a gestational age
      <30 weeks been applied. there were five (8%) babies with birth weight >1250 grams
      and eight (12%) babies with gestational age >30 weeks amongst babies with ROP but
      all were stage 1 or stage 2. All the stage 3 ROP and the threshold ROP cases were
      babies with birth weight <1000 grams and gestational age below 28 weeks.
      CONCLUSION: Ophthalmic examination may be safely and efficiently concentrated in
      babies with birth weight <1251 grams and gestational age below 30 weeks. Birth
      weight (P < 0.005) and gestational age (P < 0.01) were the only significant risk
      factors. During this 8-year period there was no significant decrease in the
      number of babies screened for ROP and the overall incidence of all stages of the
      disease has remained constant. In the present series a lower incidence of severe
      ROP was noted compared to most previous studies. Our experience from this study
      suggests the need for further refinement of screening guidelines in order to
      focus screening on the vision-threatening stages of ROP.

PMID- 12194066
TI  - The relationship between nuclear colour and opalescence on the LOCSIII scale and
      physical characteristics of cataract nuclei.
AB  - PURPOSE: To evaluate the compression characteristics of the human lens
      nucleocortex in relation to its LOCSIII clinical grading. METHODS: Sixteen
      subjects undergoing planned extracapsular cataract surgery had pre-operative slit
      lamp examination and assessment of cataract LOCSIII grade followed by
      postoperative in vitro evaluation of the nucleus with measurement of 'linear
      compressibility' by a purpose-designed caliper incorporating a strain gauge,
      enabling the derivation of a graph of nuclear compression (D (mm) against applied
      force (F (N)). RESULTS: Nuclear colour correlates with the force required to
      compress a lens to 75% of its original depth (F75) (R = 0.625, P = 0.017).
      Nuclear opalescence correlates with the force required to compress a lens to 75%
      of its original depth (R = 0.651, P = 0.012) and inversely with linear
      compressibility (DeltaD/DeltaF, the slope of the graph of nuclear compression
      against applied force) (R = -0.610, P = 0.014). F75 is a direct and linear
      compressibility is an inverse related parameter of lens nucleus 'hardness'.
      CONCLUSION: A new instrument is described which allows measurement of 'hardness'
      related compression characteristics of the human cataract in vitro. There is a
      relationship between the LOCSIII clinical classification of nuclear cataracts and
      mechanical compression characteristics of the cataractous lens. LOCSIII
      classification may aid the preoperative planning of an appropriate surgical
      approach to an individual cataract.

PMID- 12194067
TI  - Partial coherence laser interferometry vs conventional ultrasound biometry in
      intraocular lens power calculations.
AB  - AIMS: The purpose of the study was to compare optical biometry based on partial
      coherence laser interferometry (PCLI) principle to conventional ultrasound
      biometry in the accuracy of intraocular lens (IOL) power calculations. The role
      of partial coherence laser interferometry in pseudophakic axial length
      measurement was analysed in the study. METHODS: In a prospective randomised
      clinical trial, 100 patients undergoing phacoemulsification cataract surgery were
      randomised to undergo biometry by either partial coherence laser interferometry
      (IOL Master) or the applanation ultrasound technique. The IOL material, design
      and the IOL formula were standardized. The mean error and mean absolute error
      were calculated and compared using paired t-tests. RESULTS: One hundred patients
      were included in this prospective randomised trial, of whom 50 patients underwent
      optical biometry and 50 patients had biometry by applanation ultrasound. The mean
      age of patients in the PCLI group was 67 +/- 6 yrs as compared to 71 +/- 8 yrs in
      the ultrasound group (P > 0.05). The preoperative mean axial length was 23.47 +/-
      1.1 mm in the PCLI group (range 20-27.6 mm) and 23.43 +/- 1.2 mm in the
      ultrasound group with a range of 20.1-27 mm (P > 0.05). The mean absolute error
      (MAE) in the PCLI group was 0.52 +/- 0.32 D (upper and lower 95% CI 0.62 and 0.42
      respectively). The MAE in the ultrasound group was 0.62 +/- 0.4 D (upper and
      lower CI 0.73 and 0.50 D respectively). Eighty-seven per cent of patients were
      within +/- 1 D in the PCLI group as compared to 80% in the ultrasound group (P =
      0.24). The MAE of axial length difference with optical biometry was 0.13 mm +/-
      0.13 SD (range -0.42 to 0.78 mm) in the PCLI group and 0.19 +/- 0.13 mm in the
      ultrasound group. There was a mean shortening of the eye length in the PCLI group
      postoperatively. Optical biometry improved the post op refraction by 16% on
      retrospective IOL power calculations. Eight per cent failed biometry with IOL
      Master (dense cataracts (4%) and fixation instability due to macular degeneration
      (4%)). CONCLUSION: The non contact optical biometry using the partial coherence
      laser interferometry principle improves the predictive value for postoperative
      refraction and is a reliable tool in the measurement of intraocular distances in
      pseudophakic eyes.

PMID- 12194068
TI  - A survey of visual impairment in children attending the Royal Blind School,
      Edinburgh using the WHO childhood visual impairment database.
AB  - PURPOSE: To assess the aetiology and changing patterns of childhood blindness in
      one school for the blind in the UK and to assess the use of the World Health
      Organisation Prevention of Blindness (WHO/PBL) methodology and reporting form in
      a developed country. METHODS: One hundred and seven children in one school for
      the blind and visually impaired in Edinburgh were examined using the WHO/PBL
      childhood blindness assessment form. RESULTS: Of the 107 children examined, 87
      (81%) were blind or severely visually impaired (corrected visual acuity of <6/60
      (20/200) in the better eye). Perinatal related blindness (40%), hereditary
      disease (26%) and developmental factors (26%) formed the three largest
      aetiological categories. CONCLUSION: The pattern of childhood blindness seen in
      this study was similar to reports from other developed countries. The WHO/PBL
      reporting form allows detailed comparisons between countries and over time.
      Additional fields for more detailed reporting of cerebral visual impairment and
      associated handicaps would increase the usefulness of the WHO/PBL form for
      population-based studies and for use in developed countries.

PMID- 12194069
TI  - Changes in intraocular pressure following diagnostic mydriasis with
      cyclopentolate 1%.
AB  - PURPOSE: To assess the effect of diagnostic mydriasis with 1% cyclopentolate on
      the intraocular pressure (IOP) of patients attending glaucoma, medical retina and
      cataract clinics. METHODS: Levels of agreement for IOP assessment were determined
      and 95% of repeated readings found to be within +/-2 mmHg. The IOP of 83
      cataract, 87 medical retinal and 100 glaucoma patients was measured with Goldmann
      applanation tonometry before and 45 min after dilatation with 1% cyclopentolate.
      Those showing a substantial (>10 mmHg) increase in IOP underwent gonioscopy to
      determine if their angles remained open and were medically treated to lower their
      IOP. RESULTS: An approximately normal distribution of change in IOP following
      dilatation was seen in all three groups (mean change 0.4 mmHg (95% CI 0.1-0.8)).
      The proportion of patients with a rise of 5 mmHg or more in the right eye was 7%
      (95% CI 4-10%). Logistic regression using all right eyes, looking at age, sex,
      diagnosis, ethnicity, ocular medication, iris colour and lens status
      (phakic/pseudophakic/aphakic) as risk factors for a rise of IOP of 5 mmHg or more
      did not reveal any significant contribution. Correlation between results obtained
      for right and left eyes in the glaucoma group was lower (0.43) than for the other
      groups (0.66 and 0.72), but the extent to which the direction of change in one
      eye predicted that in the other was shown to be high. Two glaucoma patients with
      open angles developed a clinically important (>10 mmHg) sustained rise in IOP
      requiring treatment. CONCLUSIONS: Individual variability in the effects of
      cyclopentolate on aqueous dynamics may account for the approximately normal
      distribution of IOP seen following dilatation in all three groups. This variation
      was in excess of that due to observation error alone. It is recommended that the
      IOP be rechecked after dilation in glaucoma patients with significantly damaged
      optic nerve heads. In medical retina and cataract patients, sustained clinically
      important rises in intraocular pressure following dilation seem rarer.

PMID- 12194070
TI  - Vigabatrin associated visual field loss: a clinical audit to study prevalence,
      drug history and effects of drug withdrawal.
AB  - PURPOSE: To survey clinical visual function including quantitative manual
      perimetry results in a group of patients taking vigabatrin; to assess the
      severity of any field defects; to tabulate cumulative and daily doses of
      medication and to assess possible changes in visual function over time. METHOD: A
      prevalence study of 100 out of 183 patients currently attending a tertiary
      referral epilepsy centre who were taking or had recently discontinued vigabatrin
      (duration 83-3570 days; mean 1885 days) as part of combination anticonvulsant
      therapy. Complete neuro-ophthalmic examination including Goldmann kinetic
      perimetry was performed and monocular mean radial degrees (MRD) to the I/4e
      isopter calculated. Patients were followed up at 6-monthly intervals for not less
      than 18 months. RESULTS: Acuity and colour vision remained stable in all patients
      regardless of changes in visual fields. Twenty per cent of patients had
      significant constriction of their visual field defined as a monocular MRD of 30
      degrees or less. Males were significantly more likely to be severely affected
      than females (P < 0.01). Twenty one patients were followed after discontinuing
      vigabatrin treatment. Only three of these showed a change in MRD of 10 degrees or
      more with two deteriorating and one improving. No correlation between treatment
      duration or cumulative dosage/kg and the severity of defects could be
      demonstrated. CONCLUSIONS: Earlier reports of a high prevalence of both moderate
      and more serious field defects were confirmed in patients taking vigabatrin but
      not in epileptic patients taking other anti-convulsants. We found no evidence of
      progression or resolution of visual field defects on discontinuing the drug, and
      no relationship between dose history and visual deficit field loss. An
      idiosyncratic drug reaction within the neurosensory retina may underlie the
      pathogenesis of the visual field loss in some patients.

PMID- 12194071
TI  - The clinical characteristics of Asian and Caucasian patients on Bradford's Low
      Vision Register.
AB  - AIM: To analyse the clinical characteristics of patients on the Bradford Low
      Vision Register with regards to the type (partially sighted or blind), sex, race,
      causes and age at registration. METHODS: All the data were obtained from the
      Morley Street Resource Centre, which keeps records of all registrations in the
      Bradford Metropolitan District. Information including postcode, date of birth,
      age, gender, ethnic group, degree, date of registration, cause of registration
      and age at registration were entered into a database. RESULTS: Of all
      registrations, 64% were blind and 36% were partially sighted. Asians were younger
      at registration and there were a significantly lower number of females compared
      to Caucasians. When data were analysed for the different age groups, in the older
      group of over 65 years, Asians showed significantly more diabetic retinopathy
      (26.1%) compared to Asians (7.8%), while Caucasians demonstrated significantly
      more glaucoma (C: 29.3%; A: 17.4%). In the younger age group (<30 years), the
      leading causes for Asians were retinitis pigmentosa and nystagmus while for
      Caucasians it was congenital cataracts and optic atrophy. The proportion of
      Asians registered was significantly lower than expected from the projected
      population estimates in Bradford. CONCLUSIONS: The study indicates significant
      differences in the clinical profiles of the two racial groups. The data do not
      follow the predictions from published population estimates, with Asians,
      especially females, being under-represented in the register.

PMID- 12194072
TI  - Contact lenses in the management of high anisometropic amblyopia.
AB  - Poster at College Congress, Birmingham 2001. Oral presentation at European
      Strabismus Association, Florence 2001. PURPOSE: Anisometropia of more than one
      dioptre during the sensitive visual period may cause amblyopia. Its management
      requires refractive correction, and occlusion. Compliance with treatment is
      critical if visual improvement is to obtained. High anisometropia, poor initial
      acuity and mixed strabismic/anisometropia amblyopia are predictive factors for a
      poor outcome. We evaluated contact lens use in the management of high
      anisometropic amblyopia. METHODS: Retrospective analysis of anisometropic
      amblyopia managed in a paediatric contact lens clinic (July 1996-July 2000),
      after standard amblyopia therapy of spectacles and occlusion therapy had been
      tried. Presenting age, acuity and refraction, duration of lens wear and
      occlusion, and final visual outcomes were noted. RESULTS: Seven children (four
      male, three female) presented at age 3.5-6 years (mean 4.5). Six had myopic
      anisometropia 6.0-18.4 dioptres (mean 10.4 dioptres) and one 6.75 dioptres
      hypermetropic anisometropia. The initial corrected acuities of the amblyopic eyes
      were 6/18 to 1/60. Five patients used contact lenses with a range from 5 months
      to 4 years. Final acuities were 6/12-1/60. Two myopes with 6 dioptres
      anisometropia improved three to four Snellen lines, one with 8.8 dioptres
      improved one line. Three with >10 dioptres anisometropia did not improve. The
      hypermetropic patient improved part of one Snellen line. CONCLUSIONS: High
      anisometropic amblyopia is challenging to treat. In our study contact lenses
      improved visual acuity in myopic anisometropia of up to 9 dioptres.

PMID- 12194073
TI  - Retrobulbar circulation in patients with age-related maculopathy.
AB  - PURPOSE: To investigate retrobulbar circulation in stages of age-related
      maculopathy (ARM) and in normal fellow eyes of patients with unilateral exudative
      ARM. METHODS: Color Doppler Imaging was used to measure circulatory parameters
      (peak-systolic velocity--PSV, end-diastolic velocity--EDV, pulsatility index--PI
      and resistivity index--RI) in the central retinal, posterior ciliary and
      ophthalmic arteries of 44 patients with age-related maculopathy (ARM) and 32
      control subjects. Patients with ARM consisted of 11 with early ARM and 33 with
      late ARM. Twenty-one patients from the exudative ARM group were also included in
      a study of unilateral exudative ARM circulation. RESULTS: In the study of
      patients with ARM divided into stages, the PI and RI in the posterior ciliary
      artery of patients with late ARM were significantly higher than that of the
      control group (P = 0.0064; P = 0.0124). In the early ARM group, circulatory
      parameters did not differ significantly from those of the control group. In the
      study of unilateral exudative ARM, the affected eye showed significantly higher
      RI, as compared to the control group (P = 0.0157), and the fellow eye had
      significantly decreased EDV as compared to the control group (P = 0.0164). There
      was no significant difference in circulatory parameters between the affected and
      normal fellow eyes of patients with unilateral exudative ARM. CONCLUSION: PI and
      RI in patients with late ARM and EDV in fellow eyes of patients with unilateral
      exudative ARM showed significant changes in the posterior ciliary artery compared
      to normal controls. Altered circulation in the posterior ciliary artery may be
      involved in the pathogenesis of ARM.

PMID- 12194075
TI  - A comparative study to assess the clinical use of Fluorescein Meniscus Time (FMT)
      with Tear Break up Time (TBUT) and Schirmer's tests (ST) in the diagnosis of dry
      eyes.
AB  - INTRODUCTION: The clinical diagnosis of dry-eye is confirmed by a suitable test
      of tear production and the technique commonly used today to diagnose dry eye is
      the Schirmer's test (ST). Although the ST is easy to perform it gives variable
      results, poor reproducibility and low sensitivity for detecting dry eyes. Another
      test, the tear break up time (TBUT) is used to assess the stability of tears
      which if abnormal may also cause symptomatic dry-eye. We present the results of
      both these tests and a new test, which shows greater sensitivity than the ST in
      detecting aqueous tear deficiency. The fluorescein meniscus time (FMT) is a new
      test developed in conjunction with one of the authors (CL) and the Department of
      Ophthalmology at the University Hospital of Wales. The FMT is a measure of the
      rate at which a fluorescent tear meniscus is formed using 2% sodium fluorescein,
      a stopwatch and suitable illumination with a slit lamp. METHOD: An open
      controlled study in 62 patients and 51 controls was conducted to compare the
      ability of ST, FMT and TBUT to detect dry-eye in a group of patients diagnosed
      with rheumatoid arthritis and symptomatic dry eyes for a minimum period of 6
      months. A separate control group of 15 subjects was tested on three separate
      occasions to assess the reproducibility of the FMT test. RESULTS: All three tests
      showed a statistically significant difference between the patient and control
      populations; Mann-Whitney P < 0.001. There was a correlation between the right
      and left eye for all three tests in the control group (ST r(2) = 0.77, FMT r(2) =
      0.98, TBUT r(2) = 0.94). This correlation was markedly reduced for FMT and TBUT
      in the patient population and was in keeping with the symptoms reported as being
      worse on one side in a proportion of the patients (FMT r(2) = 0.52, TBUT r(2) =
      0.54, ST r(2) = 0.75). A correlation with age was also observed for all the three
      tests in the control group (ST r(2) = 0.74, FMT r(2)= 0.92, TBUT r(2) = 0.51),
      but not in the patient population (ST r(2) = 0.06, FMT r(2) = 0.18, TBUT r(2) =
      0.03). A significant correlation was observed between the ST and FMT in both the
      control (ST vs FMT r(2) = 0.65) and patient population (ST vs FMT r(2) = 0.44).
      There was no value greater than 200 seconds for FMT recorded in the control
      group. Using this value to define an abnormal FMT, 85% of the patients (72% of
      the eyes tested) had an abnormal result. This was in contrast to 35% of patients
      (26% of the eyes tested) with abnormal results detected by ST. Using ANOVA and
      Student's paired t-test, there were no significant differences between the three
      sets of values recorded serially over 3 months to assess the reproducibility of
      the FMT. The average standard error of the mean was 2.72% and the average co
      efficient of variation 4.07%. CONCLUSION: Our study suggests that the FMT is a
      more sensitive test with good reproducibility compared to the Schirmer's test.
      The FMT correlates with the ST and suggests that both tests measure aqueous tear
      deficiency. The FMT therefore is a better alternative to ST currently being used
      to test aqueous tear deficiency.

PMID- 12194074
TI  - Corticosteroid-induced osteoporosis in patients with uveitis.
AB  - AIMS: To estimate the prevalence of low bone density and osteoporosis in a
      population of patients with uveitis taking systemic steroid treatment; to clarify
      the risks of steroid-induced fracture and to suggest a protocol for the
      prevention and management of bone loss in patients with ophthalmic inflammatory
      disease. METHODS: Bone densitometry was performed on 129 adult patients with
      prednisolone-treated uveitis from four centres. Information on uveitis diagnosis,
      associated risk factors, steroid dosage and treatment duration, prophylaxis and
      management, was collected. Juveniles, patients with scleritis and those who had
      used deflazacort, were excluded. RESULTS: Steroid treatment time varied from 13
      weeks to 31 years, and the total dosage from 1.29 g to 166.5 g. Twenty-six
      percent of patients also used one or more immunosuppressives. Forty-eight percent
      had additional risk factors for bone loss. Bone density was abnormally low in
      44.2%, and 15.5% had osteoporosis. Osteoporosis was substantially more common in
      males (20.6%, all under 60 yrs) than in females (9.8%). Seven symptomatic
      fractures occurred in patients on treatment. Bone loss correlated with total
      steroid dose, mean dose, duration of treatment and the presence of pre-existing
      risk factors. CONCLUSIONS: The prevalence of steroid-induced osteoporosis and
      fracture is low for patients with uveitis but young males are at risk. Patients
      at high risk should be identified, and prophylaxis and treatment should be used
      as required. The guideline of the National Osteoporosis Society is recommended as
      a management protocol.

PMID- 12194076
TI  - A randomised, crossover, multicentre study to compare the performance of 0.1%
      (w/v) sodium hyaluronate with 1.4% (w/v) polyvinyl alcohol in the alleviation of
      symptoms associated with dry eye syndrome.
AB  - AIMS: To assess the safety and performance of a 0.1% (w/v) solution of sodium
      hyaluronate (HA, Fermavisc, in the alleviation of symptoms of severe dry eye in
      comparison with a 1.4% (w/v) solution of polyvinyl alcohol. METHODS: A
      randomised, crossover, multicentre study carried out at eight centres in the UK.
      Eligible patients giving written informed consent were randomised to the order in
      which they would receive the two study products. Each treatment period lasted for
      4 weeks, then the patient crossed over to the other study product. Symptoms of
      burning and grittiness were assessed by visual analogue scale (VAS) at each study
      visit and other objective clinical assessments of ocular structure and function
      were carried out at baseline and the end of each treatment period. RESULTS:
      Thirty-nine patients were entered into the study and 32 completed both treatment
      periods and were included in the statistical analyses. A significant improvement
      in the patients' VAS assessment of burning was seen after treatment with HA (P =
      0.03, 95% Confidence Interval: -23.5 to -1.1). This treatment also resulted in a
      significantly lower rose bengal staining score (P = 0.04, 95% Confidence
      Interval: -1.62 to -0.05 for the right eye). CONCLUSION: The results show a
      significant clinical benefit in terms of relief of the symptom of burning when HA
      is applied topically to the eye three or four times per day or as required. HA
      also appears to have a protective effect on the corneal epithelium, as shown by a
      reduction in the level of staining of corneal epithelial cells by rose bengal.
      This study confirms that Fermavisc is a safe and effective product for use in the
      alleviation of symptoms of severe dry eye syndrome.

PMID- 12194077
TI  - Incidence and risk factors for microbial keratitis in Hong Kong: comparison with
      Europe and North America.
AB  - PURPOSE: To establish the incidence, etiology and risk factors for microbial
      keratitis (MK) in Hong Kong. METHODS: Two hundred and twenty-three new cases of
      presumed MK were recruited over a period of 17 months and comprehensive
      microbiologic studies performed. A nested case-control study was pursued for
      patients wearing contact lenses (CLW) to determine risk factors for MK with
      regards to types of CLW and hygiene practice. RESULTS: Of the 223 patients
      recruited, 59 (26%) wore contact lenses. Corneal scrapes yielded positive
      cultures from 77 patients (35% overall, 56 non-CLW, 21 CLW). Two hundred and six
      CLW volunteers were recruited to participate in the case-control study, of whom
      135 were matched with 45 CLW patients. The annual incidence of MK was 0.63 per
      10,000 population and 3.4 per 10,000 CLW with rates for daily, extended and rigid
      lens wear of 3.09, 9.30 and 0.44 per 10,000 CLW respectively. Pseudomonas
      aeruginosa was the dominant bacterial pathogen. Six cases of Acanthamoeba
      keratitis occurred, five in CLW (incidence 0.33 per 10,000 CLW) and one following
      corneal abrasion. Non-CLW developed MK at a peak age of 73, which is 10 years
      younger than expected for Scotland and USA. CONCLUSIONS: Previous ocular surface
      disease and trauma were the main risk factors for MK in Hong Kong. CLW appears at
      least as safe as that found in Scotland and the USA. Acanthamoeba keratitis was
      detected but with an incidence rate five times lower than Scotland. Factors
      predisposing hydrogel CLWs to MK, that were statistically significant, included
      overnight wear, poor hygiene and smoking.

PMID- 12194079
TI  - Organ-cultured corneal grafts from septic donors: a retrospective study.
AB  - PURPOSE: To evaluate the quality of corneal grafts from donors, who have died
      from septic multi-organ failure and who are called septic donors in the
      following. METHODS: One hundred and eighty-two corneal grafts from septic donors
      were stored in organ culture for 10-14 days. Graft evaluation was performed
      according to the criteria of the European Eye Bank Association. Only donor
      corneas with cell density values above 2000 cells/mm(2) were transplanted. Ninety
      one patients who received these transplanted corneas were examined
      retrospectively with special emphasis on endophthalmitis, graft failure and
      incidence of immune reactions. RESULTS: Ninety-one of 182 donor corneas (50%)
      from septic donors were discarded mainly due to endothelial damage (61; 67%).
      Only seven (8%) were discarded due to medium contamination. In contrast, 452 of
      1261 donor corneas (36%) from non-septic donors during the same period were
      discarded, again mainly due to endothelial damage (264; 58%). In this group, 48
      donor corneas (11%) were discarded due to medium contamination. No patient who
      had received a graft from a septic donor has experienced endophthalmitis. The
      rate of immune reactions and graft failure was in the same range when compared to
      a larger group who received grafts from non-septic donors. CONCLUSION: Our data
      reveal no contraindication against the use of corneal grafts derived from septic
      donors, critical graft assessment in organ culture provided.

PMID- 12194078
TI  - Overexpression of p53 tumor suppressor gene in pterygia.
AB  - PURPOSE: To assess p53 gene expression in pterygia with and without recurrence.
      The pathogenesis of pterygium has not yet been determined. The most widely
      recognized etiologic factor is ultraviolet radiation, which leads to degeneration
      of the conjunctiva. However, pterygium was recently found to have several tumor
      like characteristics. The p53 gene is a common marker for neoplasia, and is known
      to control cell cycle, cell differentiation and apoptosis. In this study we
      examined the expression of the p53 gene in primary pterygia with and without
      recurrence, searching for the pathogenesis of this very common lesion and for a
      prognostic factor for recurrence. METHODS: Immunohistochemical staining using a
      monoclonal antibody to human p53 (DO-7) was performed on 13 consecutive patients
      with primary pterygia, four pterygia without recurrence and nine pterygia which
      recurred during a 12-month follow-up. As a control we used two specimens of
      normal conjunctiva. RESULTS: Seven of the 13 pterygia specimens (54%) were
      positive for abnormal p53 expression. There was no difference between the groups
      with and without recurrence. Two out of four pterygia (50%) without recurrence
      and five out of nine (55.5%) pterygia with recurrence were positive. No
      pathological staining was observed in the control specimens. CONCLUSIONS: In this
      study, abnormal p53 expression was found in pterygial epithelium, suggesting that
      pterygium could be a result of uncontrolled cell proliferation, and not as a
      degenerative lesion. There seems to be no connection between abnormal p53
      expression and recurrence.

PMID- 12194080
TI  - Dilated pupils and loss of accommodation following diode panretinal
      photocoagulation with sub-tenon local anaesthetic in four cases.
AB  - AIM: To describe pupillary abnormalities associated with diode laser
      photocoagulation with subTenon's local anaesthetic. METHODS: We describe four
      cases of tonic pupils following diabetic panretinal photocoagulation with
      subTenon's local anaesthetic. RESULTS: Six pupils of four patients became dilated
      and sustained loss of accommodation with denervation hypersensitivity with 0.1%
      pilocarpine after undergoing panretinal photocoagulation with a subTenon's local
      anaesthetic. The numbers of burns were not excessive and in one patient it even
      occurred after only 1200 laser burns. CONCLUSION: Diode laser causes histological
      changes deeper in the retina and the choroid than in Argon laser. Intense diode
      laser burns may cause damage to the short ciliary nerves traversing the choroid.
      In the unanaesthetised patient, pain arises when the laser burn hits these nerves
      and so may protect the eye from excess damage to the nerves. When the eye is
      anaesthetised with a subTenon's, local anaesthetic damage to the choroidal nerves
      may occur without the laser operator being aware that the burns are too intense.

PMID- 12194081
TI  - Uveal metastatic carcinoma in human immunodeficiency virus infection.
AB  - We report the occurrence of uveal metastatic carcinoma in two patients with
      longstanding HIV infection presenting with decreased visual acuity. In the first
      case, a 49-year-old man with a 6-year history of HIV infection presented with a 4
      5 month history of blurred vision in his right eye. In the second case, a 53-year
      old man with a 5-year history of HIV infection presented with a 3-week history of
      distorted and blurred vision in both eyes. In both cases, a choroidal metastatic
      carcinoma was ultimately discovered. To our knowledge, these are the first
      reported cases of metastatic uveal carcinoma in individuals with HIV infection.
      Currently, there have been dramatic improvements in treatment for HIV infection
      and longer survival times of infected individuals. This fact, together with
      reported increased frequencies and aggressiveness of carcinomas in HIV-infected
      individuals will likely result in increasing occurrences of uveal metastases from
      primary carcinomas in HIV.

PMID- 12194082
TI  - Ciliary body dysplasia in megalophthalmos anterior diagnosed using ultrasound
      biomicroscopy.

PMID- 12194083
TI  - Multilayered amniotic membrane transplantation for partial thickness scleral
      thinning following pterygium surgery.

PMID- 12194084
TI  - Acute posterior multifocal placoid pigment epitheliopathy with retinal vasculitis
      and papillitis.

PMID- 12194085
TI  - Angioid streaks with congenital hypertrophy of the retinal pigment epithelium: an
      association or a mere coincidence?

PMID- 12194086
TI  - Gonococcal keratoconjunctivitis in adults.

PMID- 12194087
TI  - Topical and intralesional interferon therapy for recurrent lacrimal papilloma.

PMID- 12194089
TI  - Unilateral lattice dystrophy in an elderly patient.

PMID- 12194088
TI  - Acute suprachoroidal haemorrhage with acute angle closure glaucoma as a
      presenting sign of chronic myelomonocytic leukemia.

PMID- 12194090
TI  - Chiasmal cavernous angioma. A rare case of progressive visual loss.

PMID- 12194091
TI  - Central retinal vein occlusion associated with Sturge Weber syndrome.

PMID- 12194092
TI  - The origin of posterior vitreal gas bubbles following the high velocity impact of
      a metallic fragment.

PMID- 12194093
TI  - Palliative vitrectomy for intraocular metastasis from cutaneous melanoma.

PMID- 12194094
TI  - Bilateral acute angle-closure glaucoma after use of Fenox nasal drops.

PMID- 12194095
TI  - Globe perforation by the second peribulbar injection.

PMID- 12194096
TI  - Optic disc morphology on presentation of chronic glaucoma.

PMID- 12194097
TI  - Malignant glaucoma following needling of a trabeculectomy bleb.

PMID- 12194098
TI  - Spontaneous suprachoroidal haemorrhage in a patient with age-related macular
      degeneration on excessive anticoagulation therapy.

PMID- 12194100
TI  - Pupillary distortion and staphyloma following transscleral contact diode laser
      cyclophotocoagulation: a clinicopathological study of three patients.

PMID- 12194099
TI  - Orbital nodular-granuloma annulare in a juvenile diabetic.

PMID- 12194101
TI  - Evaluation of a disposable prism for applanation tonometry.

PMID- 12194103
TI  - Wegener's granulomatosis presenting with amaurosis fugax.

PMID- 12194104
TI  - Re: One stop cataract surgery: the Bristol Eye Hospital experience 1997-1999. Eye
      2001; 15: 306-308.

PMID- 12194105
TI  - The National Survey of trabeculectomy. II. Variations in the operative technique
      and outcome.

PMID- 12194106
TI  - Mini-autograft for pterygium surgery.

PMID- 12194111
TI  - The cost-effectiveness of treatment for congenital diaphragmatic hernia.
AB  - BACKGROUND/PURPOSE: The cost-effectiveness of medical interventions is becoming
      an important issue for decision makers. Until recently, evidence of the cost
      effectiveness of neonatal surgery was largely lacking. The authors analyzed the
      cost-effectiveness of neonatal surgery and subsequent treatment for congenital
      diaphragmatic hernia (CDH). METHODS: Both costs incurred inside and outside the
      health care sector (eg, out-of-pocket expenses and productivity losses) were
      included. Quality-adjusted life years (QALYs) were measured using the EuroQol EQ
      5D questionnaire. Descriptive quality-of-life data were collected using a disease
      specific questionnaire. Both costs and effects basically were measured in a life
      time setting. RESULTS: Total costs of treatment average euro 42,658, mainly
      consisting of costs of the initial hospitalization. Productivity losses in both
      the patients and their caregivers appear to be minor. Treated CDH patients, even
      adults, suffer from respiratory difficulties and stomach aches. According to the
      EQ-5D, however, their quality of life does not differ from the general
      population, suggesting that these symptoms barely affect overall quality of life.
      Treatment results in a gain of 17.5 QALYs. Costs per QALY amount to euro 2,434.
      CONCLUSIONS: Treatment for CDH has favorable cost-effectiveness. Considering the
      growing importance of cost-effective medicine, these are important and
      encouraging results. Health economics outlines the inevitability of making
      choices that directly affect patient care and places relative values on different
      health care programs. The results of this study provide convincing evidence that
      treatment for CDH is indeed cost effective.

PMID- 12194112
TI  - Effect of mechanical ventilation on the pulmonary expression and production of
      elastin in nitrofen-induced diaphragmatic hernia in rats.
AB  - BACKGROUND/PURPOSE: Hypolastic lung in congenital diaphragmatic hernia (CDH)
      shows markedly thickened alveolar walls, increased interstitial tissue, and
      markedly diminished alveolar air space, showing morphologic immaturity. Decrease
      in lung compliance and distensibility often is seen in human CDH as well as
      experimentally produced CDH. Collagen and elastin, critical components of the
      lung connective tissue, have been suggested to have important influence on lung
      compliance and maximal expansion. The barotrauma caused by mechanical ventilation
      is known to produce structural changes in the pulmonary architecture. The aim of
      this study was to investigate the expression and production of elastin in the
      lung in newborn rats with CDH during mechanical ventilation. METHODS: CDH was
      induced in rat embryos after administration of nitrofen to pregnant dams on day
      9.5 of gestation. Cesarean section was performed on day 21 of gestation. The
      newborn rats were intubated using a 24-gauge Teflon catheter. After ligation of
      the umbilical cord, the intubated animals were transferred immediately to a warm
      plate and connected to a modified ventilator. Ventilation was continued for a
      maximum of 6 hours. The relative amount of soluble elastin in the lung was
      assessed using an enzyme-linked immunosorbent assay (ELISA) technique. Reverse
      transcription polymerase chain reaction (RT-PCR) was performed to evaluate the
      relative amount of tropoelastin mRNA expression in the lung. RESULTS: Elastin
      mRNA in the CDH lung was increased significantly (P <.01) at one hour after
      ventilation compared with ventilated controls. Elastin protein significantly
      increased in the CDH lung at one hour (P <.01) and 6 hours (P <.01) after
      starting ventilation compared with controls. CONCLUSION: The data show that
      during mechanical ventilation, elastin production is increased significantly in
      the CDH lung, and this may further affect lung compliance.

PMID- 12194113
TI  - Thyroid transcription factor-1 expression during normal human lung development
      and in patients with congenital diaphragmatic hernia.
AB  - BACKGROUND/PURPOSE: Thyroid transcription factor-1 (TTF-1) was detected in human
      respiratory epithelial cells from 11 weeks of gestation. TTF-1 is involved in
      both lung morphogenesis and in the regulation of surfactant proteins. Recently,
      low expression of TTF-1 in the nitrofen rat model of congenital diaphragmatic
      hernia (CDH) was shown and restoration of this downregulation by antenatal
      glucocorticolds (CS) was reported. The aim of this study was to investigate the
      expression of TTF-1 as a marker of lung morphogenesis in normal human lung
      development and in age-matched controls of human lung specimen in hypoplastic
      lungs of human CDH and other forms of lung hypoplasia. METHODS:
      Immunohistochemistry by a monoclonal TTF-1 antibody was performed on paraffin
      sections of human fetal and neonatal lung tissues. The so-called developmental
      group (12 weeks' gestation to full term) included 47 lung specimens. The
      congenital hypoplasia group included 8 full-term CDH patients who died within 12
      hours after birth, 3 full-term CDH patients who had antenatal CS therapy, and 4
      full-term CDH patients after extracorporeal membrane oxygenation (ECMO) therapy.
      For comparison, 6 full-term born patients, who died of other forms of pulmonary
      hypoplasia, were used as comparative specimen. Immunohistochemical localization
      of TTF-1 was evaluated by light microscopy for 3 different areas of the airways
      including intrapulmonary bronchi, intermediate airways so-called terminal
      bronchioles, distal airways, and later sacculi and alveoli. RESULTS: Nuclear TTF
      1 staining was observed in the progenitor cells of the developing bronchiolar
      cells early in the human lung developmental series. At full term, TTF-1 was
      expressed in both type II epithelial cells and in subsets of respiratory
      nonciliated bronchiolar epithelial cells in a pattern similar in all studied
      groups. No TTF-1 expression was detected at the level of the intrapulmonary
      bronchi. CONCLUSIONS: No difference in TTF-1 expression was observed in the
      developing early fetal and full-term neither in hypoplastic human lungs. This
      expression did not change with antenatal CS and postnatal ECMO treatment.
      Although TTF-1 appears to play an important role in lung morphogenesis, a pivotal
      role in human lung development is not likely.

PMID- 12194114
TI  - Nitrofen inhibition of pulmonary growth and development occurs in the early
      embryonic mouse.
AB  - BACKGROUND/PURPOSE: It was believed previously that pulmonary hypoplasia in
      congenital diaphragmatic hernia (CDH) was a consequence of the herniation of
      abdominal viscera into the chest. Using the murine nitrofen-induced model of CDH,
      the authors evaluated lung growth and development before diaphragm closure or
      herniation. METHODS: The authors examined nitrofen-exposed early embryonic lungs
      on embryonic day 12 (E12). Branching morphogenesis was quantified before and
      after 4 days in culture in serumless chemically defined media and compared with
      age-matched control lungs. The mRNA expression of proliferative and developmental
      markers in cultured lungs was then determined. RESULTS: Nitrofen-exposed lungs
      had 30% fewer total terminal branches than age-matched controls (9.3 +/- 1.9
      nitrofen v 13.7 +/- 2.6 control; P <.001). Hypoplasia also was more profound in
      the left than the right lung. These effects persisted after culturing the lungs
      for 4 days in serumless chemically-defined media (31.7 +/- 6.8 nitrofen v 42.9 +/
      8.4 control, P <.001). Furthermore, the mRNA expression of proliferative and
      developmental markers was decreased in nitrofen-exposed E12 lungs cultured for 4
      days (as a percentage of age-matched controls): cyclin A (69.28%; P =.04), Nkx2.1
      (44.4%, 0.04), SP-A (24.1%; P =.008), SP-B (23.4%; P =.05), SP-C (20%; P =.06),
      and CC-10 (13.8%; P =.04). CONCLUSION: Nitrofen induces primary pulmonary
      hypoplasia and immaturity in the early embryonic mouse, and this effect persists
      in culture.

PMID- 12194115
TI  - Congenital diaphragmatic hernia in Scandinavia from 1995 to 1998: Predictors of
      mortality.
AB  - BACKGROUND/PURPOSE: There is a lack of large contemporary studies on the
      management of congenital diaphragmatic hernia (CDH), and the prediction of
      mortality remains difficult. The aim of this study was to investigate the
      influence of perinatal factors on mortality rate in a contemporary multicenter
      study. METHODS: The authors conducted a retrospective multicenter cohort study.
      Twelve of 13 Scandinavian pediatric surgical centers participated in the study.
      During a 4-year period (1995 through 1998) 195 children with CDH were included.
      The main endpoints were hospital mortality rate and total mortality rate (before
      2001). Bivariate and multivariate survival analyses were performed using Kaplan
      Meier plots, Log-rank test, and Cox regression. RESULTS: Overall hospital
      mortality rate was 30%. Among 168 neonates with symptoms within 24 hours (early
      presenters) 35% died before discharge. All 61 deaths occurred in 157 neonates
      with symptoms within the first 2 hours of life. Among early presenters, 27% had
      prenatal ultrasound diagnosis, 26% were delivered by cesarean section, and 21%
      had associated major malformations. Bivariate analysis of early presenters showed
      increased risk of death in neonates with prenatal diagnosis, associated
      anomalies, right-sided diaphragmatic hernia (RCDH), low 1-minute and 5-minute
      Apgar scores, low birth weight, short gestational age, and cesarean delivery.
      Neonates with prenatal diagnosis were characterized by significantly lower Apgar
      scores, lower birth weight, and increased frequency of associated anomalies than
      those diagnosed after birth. Multivariate analysis found that prenatal diagnosis
      (P =.004), 1-minute Apgar (P =.001), and RCDH (P =.042) were independent
      predictors of total mortality rate. CONCLUSIONS: In a series of 195 CDH patients,
      all 61 deaths occurred in the 157 neonates presenting with symptoms within the
      first 2 hours of life. Prenatal diagnosis, 1-minute Apgar score, and RCDH were
      significant independent predictors of total mortality.

PMID- 12194116
TI  - Submuscular bar, multiple pericostal bar fixation, bilateral thoracoscopy: A
      modified Nuss repair in adolescents.
AB  - BACKGROUND/PURPOSE: Thoracoscopic Nuss repair of funnel chests is used
      increasingly, but has a high bar dislocation rate. The authors intended to reduce
      this by technical modifications of the original Nuss technique. METHODS: In 40
      patients from 12.3 to 42.1 years of age (mean, 17.6 +/- 5.8) the bars were placed
      directly on the ribs in a submuscular position and fixed by a minimum of 14
      absorbable figure of 8 sutures around the bar and the underlying rib placed under
      bilateral thoracoscopy. Two stabilizers were used in all patients, the bar was
      introduced from the left in severe cases, and a second bar was implanted in most
      beyond 16 years of age. All patients underwent follow-up to date in a prospective
      observation study. RESULTS: There was no bar or stabilizer dislocation, no
      prolonged pain or neuralgia, but one traumatic seroma, one pleural, and one
      pericardial effusion. One bar was easily removed after 13 months. CONCLUSIONS:
      Submuscular position provides a far better bar fixation and soft tissue coverage
      of Nuss implants. The technique is technically more demanding but safe and has
      reduced the incidence of bar dislocation to zero in this early experience of 40
      adolescent patients, although no sportive restrictions were imposed on the
      patients at all.

PMID- 12194117
TI  - Treatment of pectus excavatum with bioabsorbable polylactide plates: Preliminary
      results.
AB  - BACKGROUND/PURPOSE: Pectus excavatum usually is corrected by thoracoplasty using
      metal plates. Recently bioabsorbabe polylactide plates have been developed. The
      aim of this study was to compare outcome after use of metal and bioasorbable
      plates in thoracoplasty performed for correction of pectus excavatum. METHODS:
      Eighty-three children (<16 years old) underwent thoracoplasty (Sulamaa's
      technique). In 75 patients, metallic plates, and in 8 patients, self-reinforced
      poly-L-lactide (SR-PLLA) plates, were used. Seven patients in the SR-PLLA group
      and 13 patients in the metal plate group were assessed 0.5 to 13 years
      postoperatively. RESULTS: The mean operating time was 121 minutes in the metal
      plate group, and 87 minutes in the SR-PLLA plate group. In the metal plate group,
      complications were pain caused by instability of the metal plates (n = 17), wound
      infection (n = 3), recurrence of deformity (n = 3), postoperative pain (n = 3),
      pneumothorax (n = 1), and nonspecific postoperative fever (n = 1). Thirteen
      patients underwent reoperation to refix the position of the metallic plates. In
      the SR-PLLA group, one case of pneumothorax occurred, and plate fragment
      palpability caused local pain in one patient. Cosmetic results and lung function
      values were similar. CONCLUSION: Our preliminary results show that bioabsorbable
      plates are a useful option in the treatment of pectus excavatum in children.

PMID- 12194118
TI  - Benefits of early diagnosis and preemptive treatment of biliary tract
      complications after major blunt liver trauma in children.
AB  - BACKGROUND/PURPOSE: Nonoperative management of blunt liver trauma may delay
      diagnosis of related biliary complications leading to delayed surgical
      intervention and related morbidity. The aim of this study was to see whether
      technetium (tc) 99 trimethylbromo-im-indolacetic acid (TBIDA) nuclear scan would
      allow noninvasive early diagnosis of bile leak and pre-emptive management.
      METHODS: Retrospective analysis of the patient records and radiologic
      investigations of 7 patients admitted between April 1998 and December 2000 with
      "major" blunt liver trauma (parenchymal fracture of less than 4 cm on computed
      tomography [CT] scan or involving porta hepatis) and various types of biliary
      complications. Patients with or without early TBIDA diagnosis were compared.
      RESULTS: There were 7 patients. The first 2 patients were treated conventionally
      without TBIDA, and late diagnosis was associated with further related problems
      (sepsis, life-threatening hemorrhage in both cases) and prolonged hospital stay.
      The subsequent 5 consecutive patients benefited from early diagnosis (TBIDA scan,
      2 to 4 days after trauma), and preemptive management was done (tailored to each
      case). There was no further or related morbidity. All 7 patients currently are
      alive and well. CONCLUSIONS: A TBIDA nuclear medicine scan was efficient in
      providing an early diagnosis of biliary leakage, thus, allowing adequate
      preemptive management. In turn, this may have helped avoid related added
      morbidity compared with cases of late diagnosis. Early TBIDA scan should be
      performed routinely when the initial CT scan confirms liver trauma graded as
      "major."

PMID- 12194120
TI  - Effects of irradiated tumor vaccine and continuous localized infusion of
      granulocyte-macrophage colony-stimulating factor on neuroblastomas in mice.
AB  - BACKGROUND/PURPOSE: Immunomodulatory treatment has been proposed as a feasible
      strategy for neuroblastoma treatment. In this study, the antitumor effects of a
      continuous localized subcutaneous infusion of granulocyte-macrophage colony
      stimulating factor (GM-CSF) into the injection site of irradiated tumor vaccine
      used as a source of tumor antigens on mouse neuroblastoma were investigated.
      METHODS: A/J mice were inoculated subcutaneously with wild type neuro-2a
      neuroblastoma cells and then treated with 5 doses of irradiated tumor vaccine or
      continuous localized infusion of GM-CSF (1 ng/d or 10 ng/d) via an osmotic
      minipump. Survival rates and survival times were compared among the groups. Tumor
      growth rates and animal survival times were followed and compared among different
      groups. Histologic and immunohistochemical analyses were performed to observe the
      immune response induced by various treatment strategies. RESULTS: Tumor growth
      rates were reduced significantly and survival times prolonged significantly by
      the treatment using tumor vaccine and continuous infusion of 10 ng/d of GM-CSF
      when compared with the control group (P <.05). One mouse treated with tumor
      vaccine and a 10 ng/d infusion of GM-CSF showed tumor regression and long-term
      survival, and no tumor growth was noted after rechallenge with wild-type neuro-2a
      cells. In contrast, using tumor vaccine only, or tumor vaccine combined with a 1
      ng/d infusion of GM-CSF was less effective than tumor vaccine combined with a 10
      ng/d infusion of GM-CSF (P <.05). Infusion of GM-CSF alone had no antitumor
      effects. Immunohistologic analyses showed significant CD4+ and CD8+ T cell
      infiltration of the tumor in the mice treated with tumor vaccine and a 10 ng/d
      infusion of GM-CSF. CONCLUSIONS: The results suggest that an irradiated tumor
      vaccine combined with continuous localized infusion of GM-CSF may induce a tumor
      specific antitumor immune response that can suppress tumor growth and prolong
      survival. Such a treatment strategy deserves consideration as a possible adjuvant
      treatment for neuroblastoma.

PMID- 12194119
TI  - Expression of the periostin mRNA level in neuroblastoma.
AB  - BACKGROUND: Neuroblastoma is the most common malignant solid tumor in early
      childhood. Whether neuroblastoma is diagnosed by mass screening or by clinical
      symptom, it has been reported to be correlated with prognosis of the disease. The
      periostin protein shares structural and sequence homology with fasciclin I, which
      is an insect adhesion molecule. METHODS: Expression of periostin messenger RNAs
      were evaluated by real-time reverse transcription polymerase chain reaction (RT
      PCR) assay in 24 tumor samples from neuroblastoma using LightCycler. The data
      were analyzed in reference to clinicopathologic factors. RESULTS: There was a
      tendency for higher periostin transcripts levels in the tumor samples from stage
      IV when compared with the stage I (P =.0845). The periostin mRNA level was higher
      in the group with disease diagnosed by symptom than in the group with disease
      diagnosed by mass screening (P =.0266). The periostin mRNA level also was higher
      in the group with disease diagnosed after 1 year of age than in the group with
      disease diagnosed before 1 year of age (P =.0059). CONCLUSION: Because the groups
      with disease diagnosed by symptom or after 1 year of age were reported to be the
      worse prognosis, the periostin mRNA expression levels were correlated with tumor
      progression or prognosis of neuroblastoma.

PMID- 12194121
TI  - Clarification of the processes that lead to anorectal malformations in the ETU
      induced rat model of imperforate anus.
AB  - BACKGROUND: Ethylenethiourea (ETU) administered to timed-pregnant rats can induce
      anorectal malformations (ARMs) in about 80% of rat fetuses, thus providing an
      ideal animal model to study the embryogenesis of ARMs. The current study was
      undertaken to investigate the embryogenetic events that may be responsible for
      the development of ARMs in rats. METHODS: Time-mated pregnant rats were divided
      randomly into control and experimental groups. The experimental rats received 1%
      ETU (125 mg/kg) by gavage on gestational day 10, and control rats received only
      the vehicle. Their embryos were harvested by cesarean section on gestational days
      13, 14, 15, and 16. They were fixed and embedded in paraffin and serially
      sectioned in either the sagittal or transverse plane. The sections were stained
      with H&E, examined, and photographed. The comparative morphogenesis of the
      hindgut, cloaca, and tailgut of age-matched embryos was studied. RESULTS: The key
      abnormalities in the experimental embryos were: (1) maldevelopment of cloaca and
      urorectal septum with no sign of the fusion between the urorectal septum and the
      cloacal membrane, (2) delay of tailgut regression, (3) abnormal and massive
      apoptotic cell death involving the posterior cloacal wall, and (4)
      underdevelopment of the dorsal aspect of the cloaca and its membrane. The type of
      ARM that was developing was discernible by gestational day 15 and 16.
      CONCLUSIONS: ARMs induced by ETU in rat embryos seem to be caused by the
      cumulative effect of aberrations in the development of several components of the
      hindgut and cloaca. Variation in the extent of maldevelopment of these structures
      may result in a spectrum of ARMs.

PMID- 12194123
TI  - Laparoscopy in children with complicated appendicitis.
AB  - BACKGROUND/PURPOSE: Laparoscopic appendectomy is an accepted way of dealing with
      suspected uncomplicated appendicitis in children. The role of laparoscopy in
      complicated acute appendicitis is more controversial. The purpose of this trial
      was to compare laparoscopic appendectomy with open appendectomy in children with
      complicated appendicitis. METHODS: A total of 102 children with suspected acute
      appendicitis were selected randomly to undergo either a laparoscopic or an open
      appendectomy. The outcomes of 25 children with complicated appendicitis, 13 in
      the laparoscopic group and 12 in the open appendectomy group, were analyzed.
      Children, their parents, and research nurses were blinded to which procedure had
      been performed and remained blinded until the control visit 7 days after the
      operation. All 25 children completed a 30-day follow-up. RESULTS: There were no
      differences in terms of patients' age, sex, weight, height, and appendiceal
      histology between the 2 groups. All laparoscopic procedures were completed
      without conversion. The mean (+/-SD) operating time was 63 (+/-31) minutes in the
      laparoscopic group and 37 (+/-18) minutes in the open appendectomy group (mean
      difference 26 minutes, 95% CI 5 to 47 minutes, P =.02). There were 2 major
      complications in the laparoscopic group in children with appendiceal masses. One
      child had an entero-cutaneous fistula of the residual appendiceal tip that needed
      open reoperation. Another child had a pelvic abscess that resolved with
      antibiotic treatment. Superficial wound infections were encountered in 2 patients
      in the open appendectomy group. CONCLUSIONS: Laparoscopic appendectomy is an
      alternative to open procedure in children with complicated appendicitis. Good
      surgical judgement is necessary in patients with an established appendiceal
      abscess.

PMID- 12194122
TI  - Randomized, placebo-controlled treatment of anal fissure by lidocaine, EMLA, and
      GTN in children.
AB  - BACKGROUND/PURPOSE: Anal fissures would result in constipation in children,
      worsening the clinical picture, thus, justifying a fast response therapy. In this
      randomized, prospective, placebo-controlled study, it was aimed to determine the
      response rates to fissure treatment by lidocaine, EMLA and GTN on the 10th day
      and after 8 weeks of therapy. Related childhood literature is scarce, and EMLA is
      tried for the first time in fissure treatment. METHODS: One hundred two children
      with anal fissures were allocated randomly into 4 groups. Placebo group (P; n =
      20) received vaseline; group L (n = 24), 10% lidocaine; group EMLA (n = 25),
      eutectic mixture of 5% prilocaine-5% lidocaine; and group GTN (n = 22), 0.2%
      glyceryl trinitrate ointment twice daily to the distal anal canal. Symptoms and
      physical findings were separately scored as 0, 1, and 2. On the 10th day, the
      number of patients with scores of 0 (unresponsive) and in the 8th week with
      scores of 2 (healed and symptom free) were analyzed statistically. RESULTS:
      Ninety-one patients completed the study. On the 10th day children with 0
      symptomatic and fissure healing scores were, respectively, 90% to 95% in group P,
      75% to 80% in group L, 20% to 40% in group EMLA, and 5% to 10% in group GTN.
      These results were statistically significant. In the eighth week, children with
      symptomatic and healing scores of 2 were, respectively, 10% to 5% in group P, 42%
      to 29% in group L, 76% to 64% in group EMLA, and 91% to 82% in group GTN. Results
      in groups GTN and EMLA were statistically similar (P >.05) and better than the
      other 2 groups (P <.05). CONCLUSION: Faster response rates could be achieved by
      GTN application, and similar and high success rates could be gained by GTN or
      EMLA by 8 weeks of treatment.

PMID- 12194124
TI  - Stooling and manometric findings after primary pull-throughs in Hirschsprung's
      disease: Perineal versus abdominal approaches.
AB  - BACKGROUND/PURPOSE: Primary pull-through via a perineal approach (PA) has
      recently been reported for Hirschsprung's disease. One criticism of this approach
      is that it requires a large amount of retraction on the anal sphincters.
      Additionally, because the procedure is new, most patients undergoing a PA are too
      young to assess long-term continence rates. This study examined early stooling
      patterns, anal sphincteric pressures, and number of enterocolitic episodes in
      infants who underwent a PA. Results were compared with a conventional combined
      transabdominal and perineal approach (TA). METHODS: Over 2 years, 26 pull-through
      procedures were performed. Nine of those were PA, and 17 were TA. Twelve of the
      26 patients had formal manometric studies postoperatively. Results are expressed
      as mean +/- SD; unpaired t test and Chi;(2) were used for statistical analysis.
      RESULTS: Mean follow-up post-pull-through was 23 +/- 2.3 months for the TA and 14
      +/- 1.9 months for the PA. Manometric resting sphincter pressure in the TA group
      averaged 79 +/- 17 mm Hg compared with 76 +/- 21 mm Hg in the PA group (P =.78).
      Number of stools per day was 3.3 +/- 0.6 in the TA group compared with 2.2 +/-
      0.3 in the PA group (P =.17). Post-pull-through enterocolitis was experienced by
      53% of the TA group (mean, 1.5 +/- 0.6 episodes) and 56% of the PA group (mean
      0.9 +/- 0.4 episodes) for a P =.08 by Chi;(2) analysis. CONCLUSIONS: Manometric
      sphincter pressure and enterocolitic episodes after a PA for Hirschsprung's
      disease appear to be similar to results obtained with a conventional TA.
      Evaluation of early stooling frequency shows a comparable frequency after a PA.
      This suggests that both methods are safe, and the PA does not appear to
      compromise sphincter integrity.

PMID- 12194125
TI  - Translevator anal anomalies with cutaneous fistulae passing deep to the scrotum.
AB  - METHODS: The authors present a series of 9 patients collected from 4 centers with
      translevator anal anomalies, each of which has a fistula tracking forward deep to
      the scrotum and opening at the peno-scrotal junction. Whereas some would appear
      to be covered ani in type, others are deeper and would appear to fit in with an
      intermediate type of classification emphasizing the idea of a "spectrum" of
      malformation. RESULTS: The anatomic arrangement, associated anomalies (eg, 2 had
      hypospadias), and surgical management is described briefly in each case. Careful
      examination may be necessary to identify the fistula. CONCLUSIONS: It is
      recommended that the surgery be individualized depending on the findings. On a
      theoretical embryologic basis there is abnormality in the formation of the outer
      genital folds, and there also may be abnormality in some cases of the inner
      genital folds.

PMID- 12194126
TI  - Protective effects of recombinant human interleukin-10 on intestines of hypoxia
      induced necrotizing enterocolitis in immature rats.
AB  - BACKGROUND/PURPOSE: The role of cytokines in the pathogenesis of hemodynamic
      instability or tissue destruction in patients with necrotizing enterocolitis
      (NEC) remains undefined. The aim of this study was to determine the effects of
      recombinant human interleukin-102 (rhIL-10) on intestines of hypoxia-induced
      necrotizing enterocolitis in immature rats. METHODS: The study was performed on 1
      day-old Sprague Dawley rat pups. Group 1 (n = 8) served as nonhypoxic controls.
      Group 2 (untreated, n = 11) rats were subjected to hypoxia-reoxygenation (H/O)
      and then were returned to their mothers. Group 3 (rhIL-10 treated, n = 10) rats
      were subjected to H/O, were returned to their mothers, and were treated with rhIL
      10 (75 microgram/kg subcutaneously) for the next 3 days. All animals were killed
      on day 4, and intestine specimens were obtained to determine the tissue level of
      malondialdehyde (MDA) and histologic changes. RESULTS: The microscopic lesions in
      the untreated rats were virtually the same as those seen in neonatal NEC, with
      destruction of villi and crypts, and in some cases extension to the muscularis.
      In contrast, in the rats treated with rhIL-10, lesions were limited essentially
      to the very tips of the villi. Intestinal injury score was significantly less in
      the rhIL-10-treated rats than in the untreated rats (P <.05). In the rhIL-10
      treated group, Malondialdehyde (MDA) levels were not significant in comparison to
      the control group. In the untreated group, MDA levels were significantly
      increased when compared with the control and the rhIL-10-treated groups (P <.001
      and P <.05, respectively). CONCLUSION: RhIL-10 has a protective effect on
      intestinal injury in NEC in an experimental model.

PMID- 12194127
TI  - Elective delayed midgut reduction-No anesthesia for gastroschisis: Selection and
      conversion criteria.
AB  - BACKGROUND/PURPOSE: In 1998 Bianchi and Dickson published their proposal for
      elective delayed midgut reduction without anaesthesia (EDMR-No GA). The study has
      been prospectively extended to develop "selection and conversion criteria" to
      ensure safe application of the technique. METHODS: In a prospective study from
      1993 to date, EDMR-No GA was considered as first-line postnatal management in 35
      children. The protocol and technique were those described by Bianchi and Dickson
      in 1998. RESULTS: EDMR-No GA was completed successfully in 25 children, of whom,
      23 are normal with an aesthetic, scarless abdomen. Two children had bowel
      necrosis and died of short bowel state. A trial EDMR-No GA was converted to a
      staged silo reduction in 2 children who are both alive and well. EDMR-No GA was
      considered contraindicated in 8. Five had an elective, staged silo reduction, 2
      had EDMR under anesthesia, and one 27-week-gestation baby died of severe
      hypothermia and acidosis before any procedure. CONCLUSIONS: No single technique
      is applicable in all circumstances, and "selection and conversion criteria" are
      relevant to safe EDMR-No GA. These include poor general condition, significant
      vital organ anomaly, bowel-to-abdomen disproportion and "at risk" bowel
      circulation. The development of distress and progressive metabolic acidosis
      during and after EDMR-No GA, are indications for urgent conversion to avoid
      serious bowel injury. Experience with EDMR-No GA hones the surgeon's sensitivity
      in assessing abdominal.

PMID- 12194128
TI  - Induction of fetal diuresis with intraamniotic furosemide increases the clearance
      of intraamniotic substances: An alternative therapy aimed at reducing
      intraamniotic meconium concentration.
AB  - BACKGROUND/PURPOSE: Contact with amniotic fluid (AF) causes intestinal damage in
      gastroschisis. Intraamniotic meconium has been shown to be responsible for
      intestinal damage, and occurrence of this damage has been shown to depend on the
      concentration of intraamniotic meconium. When intraamniotic meconium
      concentration is lowered below threshold level by exchanging AF with saline in
      gastroschisis, intestinal damage can be prevented. Theoretically, induction of
      fetal diuresis with intraamniotic furosemide may increase AF volume and fetal
      swallowing rate, thus, increase absorption of AF by intestines; therefore, the
      clearance of meconium from the AF may increase. An experimental study was planned
      to investigate the effects of intraamniotic diuretic injection on the clearance
      of intraamniotic substances. METHODS: Pregnant rabbits on the 23rd to 25th
      gestational day were divided into 2 groups as furosemide and control. Technetium
      tc99m labeled "tin colloid" was injected into the amniotic cavity, and AF sample
      was taken 10 minutes later. Furosemide was injected into the amniotic cavity
      afterwards. Two and 6 hours later, AF samples were obtained. Intestines were
      harvested at the end of the study. Control group received intraamniotic saline
      instead of furosemide. Radioactivities of the AF samples and intestines were
      determined by gamma counter. Clearance of the radioisotope from AF and intestinal
      accumulation were calculated. RESULTS: The clearance of the radioisotope from AF
      was increased significantly in the furosemide group (n = 10) compared with the
      control group (n = 8; P <.01). Gastrointestinal accumulation of the radioisotope
      in the furosemide group was 4-fold higher than that the control group (P <.01).
      CONCLUSIONS: Induction of fetal diuresis with intraamniotic furosemide
      accelerates the clearance of intraamniotic substances. This is probably caused by
      increased urinary output rate, which increases AF volume and consequently results
      in increased fetal swallowing of AF. In the diseases like gastroschisis and
      myelomeningocele, in which the contact with AF causes tissue damage, the
      elimination of meconium from AF in a somewhat natural manner like this method,
      should be studied further because it may be an alternative minimal invasive in
      utero treatment modality.

PMID- 12194129
TI  - Revision of circumcision in children: Report of 56 cases.
AB  - BACKGROUND/PURPOSE: Circumcision is the most commonly performed surgical
      procedure in the United States today. Despite the large number of specialists who
      perform this procedure, only occasionally are the results unsatisfactory. The
      purpose of this study is to review the indications for circumcision revision,
      attempt to identify the specialists who are performing unsatisfactory
      circumcisions, describe the authors' surgical technique for circumcision
      revision, and review current coding and billing issues related to this procedure.
      METHODS: The authors reviewed the charts of 56 consecutive children who underwent
      circumcision revision over a 4-year period (1995 to 1999). They also reviewed
      their current coding and billing practices for this procedure. RESULTS: Children
      undergoing revision of circumcision ranged in age from 6 weeks to 11 years with a
      mean of 26.7 months. Redundant foreskin was the most common indication for
      circumcision revision. In 38 patients (68%) the authors were able to identify the
      specialist who performed the procedure. Pediatricians were most commonly
      identified (n = 26), followed by residents in training (n = 10) family physician
      (1), and nurse midwife (1). The authors were unable to identify the type of
      neonatal circumcision originally performed. Their surgical procedure was the
      conventional sleeve technique without variation in 55 cases. A gomco clamp was
      utilized in one patient under local anesthesia and resulted in significant
      difficulty in the performance of the revision. All patients had a satisfactory
      cosmetic outcome. There was one complication in a child who required a return to
      the operating room for postoperative bleeding and hematoma. In review of the
      authors coding practices they found that there was an appropriate diagnosis code
      available for redundant foreskin but a specific procedure code was lacking before
      2002. The authors also found that midwives perform circumcisions throughout the
      United States. CONCLUSIONS: Considering the number of neonatal circumcisions
      performed in the United States, revision of circumcision uncommonly is required.
      The most common indication for circumcision revision is redundant foreskin.
      Although pediatricians were most commonly implicated in this study as the source
      of unsatisfactory circumcisions, that finding probably is more a reflection of
      local practices and referral patterns. Our recommended surgical procedure, the
      conventional sleeve technique, is familiar to pediatric surgeons, produces a
      satisfactory cosmetic result, and is easy to teach to residents and fellows. The
      authors do not recommend the use of a gomco clamp for circumcision revision. The
      authors do not feel that a circumcision revision should be delayed expecting that
      the child will grow into the redundant foreskin. Appropriate diagnosis codes have
      been available, but a new and more specific procedure code has just been
      introduced in 2002.

PMID- 12194130
TI  - Correction of congenital chordee penis by 'ventral separation and outward
      rotation of corpora'.
AB  - BACKGROUND/PURPOSE: The formation of congenital chordee penis in patients with or
      without hypospadias is multifactorial and not completely clear. In most cases,
      after release of all known causes of chordee, "residual" penile curvature can
      persist. The authors discuss the etiopathogenetic mechanisms of congenital
      chordee penis and describe their experience in surgical correction of "residual"
      penile curvature by "ventral separation and outward rotation of corpora."
      METHODS: In 22 patients with congenital chordee penis with or without
      hypospadias, "residual" penile curvature was corrected by "ventral separation and
      outward rotation of corpora." RESULTS: Ventral separation and outward rotation of
      corpora resulted in satisfactory correction of penile curvature. In only 2 cases
      of chordee penis without hypospadias was further intervention necessary: a
      Nesbit's plication was carried out in one and a neourethra placed in the other.
      At follow-up no residual penile curvature was observed. CONCLUSIONS: An arrest of
      development of the penis caused by failure of outward ventral rotation of the
      corpora, may contribute to the formation of chordee penis. When "residual" penile
      curvature persists, "ventral separation and outward rotation of corpora" can be
      used to correct this complex malformation.

PMID- 12194131
TI  - Unusual presentations of pouch colon.
AB  - Pouch colon associated with high anorectal malformation is a rare anomaly. Two
      unique anatomic variants of congenital pouch colon, never reported before, are
      presented.

PMID- 12194132
TI  - Complete bladder exstrophy with a normal phallus: A variant of superior vesical
      fissure.
AB  - Variations in the anatomic defects of the bladder exstrophy are well recognized,
      but their incidence is extremely low. Here the authors describe a rare case of
      superior vesical fissure in which a relatively large defect caused the whole
      bladder to prolapse outside. A review of literature found only 2 other cases that
      resembled our case. This particular variation of exstrophy is not only important
      owing to its extreme rarity but also raises a question for an embryologic
      explanation.

PMID- 12194133
TI  - Parasitic omphalopagus complicated by omphalocele and congenital heart disease.
AB  - Conjoined twins occur in approximately one of every 50,000 to 200,000 births.
      Atypical or parasitic conjoined twins result from the embryonic death of one
      twin, which leaves behind body parts vascularized by the primary twin.
      Omphalopagus refers to conjoined twins joined at the level of the umbilicus. The
      authors report a case of atypical omphalopagus involving an acardiac, acephalic,
      parasitic twin and a host twin with a large omphalocele, transposition of the
      great arteries, and aortic coarctation. The authors briefly review reported cases
      of parasitic omphalopagus and emphasize the role of intensive neonatal care,
      preoperative planning, and staged surgical intervention in the successful
      management of complicated variants.

PMID- 12194134
TI  - Bilateral ovarian autoamputation in an infant.
AB  - A case of bilateral ovarian autoamputation in an asymptomatic infant is
      presented. Cystic lesions were detected within the abdomen of the fetus during
      antenatal ultrasound scan (USS). USS performed shortly after birth showed a
      single lesion thought to be a duplication cyst, but at laparotomy 2 free floating
      cysts representing the ovaries were discovered. A review of the natural history
      of neonatal ovarian cysts and the management is given.

PMID- 12194136
TI  - Esophageal achalasia and hypertrophic pyloric stenosis associated with a
      phytobezoar in an adolescent.
AB  - Esophageal achalasia is an uncommon condition in children. The authors report on
      a 14-year-old girl who showed a very unusual association of cardiospasm and
      hypertrophic pyloric stenosis with a gastric phytobezoar.

PMID- 12194135
TI  - Abdominal pain and ketonuria in an 11-year-old girl five months after abdominal
      trauma.
AB  - Five months after an abdominal trauma, a 11-year-old girl was admitted for
      abdominal pain, hyperglycemia, and ketonuria, which led to the diagnosis of left
      diaphragmatic rupture with gastric necrosis and perforation. The girl died soon
      after operation.

PMID- 12194137
TI  - Vaginal reconstruction in a patient with rhabdomyosarcoma previously treated by
      total vaginectomy.
AB  - In vaginal rhabdomyosarcoma, because of effectiveness of multiple-agent
      chemotherapy and brachytherapy, function-preserving treatment without radical
      surgery has been recently recommended. However, for patients with persistent or
      recurrent tumors, vaginectomy with or without hysterectomy is appropriate. The
      authors report experience of successful vaginal reconstruction in a
      rhabdomyosarcoma patient who had total vaginectomy with preservation of the
      uterus. Because continuity from the vaginal introitus to the uterus was
      established, fertility can be expected for this patient.

PMID- 12194138
TI  - Treatment of high imperforate anus with large omphalocele in a baby boy.
AB  - Synchronous treatment of high imperforate anus with large omphalocele is a
      challenge for pediatric surgeon. A case of this unusual condition in a male
      neonate is presented. The high imperforate anus was repaired by primary one-stage
      posterior sagittal anorectoplasty, and the omphalocele was treated
      nonoperatively. Recovery was uneventful.

PMID- 12194139
TI  - The use of endoscopic ultrasound in the diagnosis of solid pseudopapillary tumors
      of the pancreas in children.
AB  - Since the first description by Frantz in 1959 of a papillary cystic tumor of the
      pancreas, solid pseudopapillary tumors have been increasing in incidence.
      However, management of these lesions remains controversial. Patients under the
      age of 20 years more often undergo local excision than do their older
      counterparts, resulting in increased recurrence rates. The cause of this
      discrepancy is not clear but may be related to an inability to make a definitive
      preoperative diagnosis. The authors report a case of a solid pseudopapillary
      tumor of the pancreas in a 13-year-old girl in which the diagnosis was
      established preoperatively by endoscopic ultrasound scan with fine-needle
      aspiration (EUS-FNA). EUS-FNA represents a diagnostic technique commonly used in
      adults that may be useful in identifying the rare pediatric patient with
      pancreatic malignancy.

PMID- 12194140
TI  - Cholelithiasis and perforated gallbladder in an infant.
AB  - An infant presented with abdominal distension and failure to thrive. This patient
      was a 3.5-month-old, ex-26-week premature infant at the time of presentation who
      required supplemental parenteral nutrition until day 9 of life. Workup found
      ascites and a complex cystic mass in the porta hepatis. A perforated gallbladder
      with gallstones was found at laparotomy. The gallstones were removed, and the bed
      of the gallbladder was drained. Output from the drain was minimal by
      postoperative day 6, and the drain subsequently was removed. The child did well
      postoperatively; hematologic and metabolic workups were unrevealing. Perforation
      of the gallbladder is an exceedingly uncommon finding in infants. Appropriate
      management includes laparotomy and drainage of the gallbladder bed.

PMID- 12194141
TI  - Congenital pouch colon: Massive redilatation of the tubularized colonic pouch
      after pull-through surgery.
AB  - BACKGROUND/PURPOSE: Children with a type I/II congenital pouch colon (CPC)
      malformation associated with imperforate anus usually are treated by subtotal
      excision of the colonic pouch, tubularization of the remaining portion, and pull
      through of the tubularized colon during definitive surgery. The authors report 3
      patients treated in this fashion who presented 2 to 10(1/2) years later with
      massive redilatation of the previously tubularized colon and enterocolitis
      METHODS: There were no anal strictures or malpositioning of the pulled through
      bowel. Contrast enema showed massive redilatation of the colonic pouch. Near
      total excision of the redilated pouch with anastomosis of normal proximal
      ileum/colon with the retained distal portion of the pouch was performed by the
      abdominal approach. RESULTS: Anastomotic leaks occurred in 2 patients but were
      treated successfully. Postoperatively, the patients had relief from their
      abdominal symptoms and improvement in fecal continence. CONCLUSIONS: The colonic
      pouch in CPC has a marked tendency to undergo redilatation, even after
      tubularization. The surgical procedure described here for the treatment of these
      patients appears to be satisfactory.

PMID- 12194142
TI  - Analysis of gastroesophageal reflux.

PMID- 12194144
TI  - In utero meconium exposure increases spinal cord necrosis in arat model of
      myelomeningocele.

PMID- 12194146
TI  - In utero meconium exposure increases spinal cord necrosis in arat model of
      myelomeningocele.

PMID- 12194147
TI  - Calcified abdominal aortic aneurysm in a 12-year-old boy.
AB  - The authors report a case of an idiopathic, isolated infrarenal abdominal aortic
      aneurysm with dense intramural calcification and sterile mesenteric
      lymphadenopathy in a 12-year-old boy. Aneurysmal disease in the pediatric
      population is very uncommon. The majority of previously reported cases have clear
      associated causes, such as connective tissue disorders, infectious processes,
      inflammatory states, or trauma. A minority of cases have no distinguishable cause
      and are classified as idiopathic. Isolated abdominal aortic aneurysms are very
      uncommon in children, and those with densely calcified walls are rare, with only
      2 case reports in the literature. The authors found no previous reports of
      abdominal aortic aneurysm with associated sterile mesenteric lymphadenopathy. The
      etiology of this patient's aneurysm remains unknown.

PMID- 12194148
TI  - Heterotopic brain tissue in the upper lip of a neonate mimicking bilateral cleft
      lip features.
AB  - Heterotopic brain tissue is an extremely rare developmental anomaly frequently
      diagnosed in the newborn period. This entity has been described in various sites
      of the head and neck, most commonly in the nasal area. Computed tomography and
      magnetic resonance imaging are necessary for exclude associated cranial
      communications. Heterotopic brain tissue is an extremely rare developmental
      anomaly frequently diagnosed in the newborn period. This entity has been
      described in various sites of the head and neck, most commonly in the nasal area.
      Computed tomography and magnetic resonance imaging are necessary for exclude
      associated cranial communications.

PMID- 12194149
TI  - Pseudoexstrophy associated with megalourethra.
AB  - Pseudoexstrophy is a rare exstrophy variant that has musculoskeletal stigmata of
      the exstrophy complex without any associated defect in the urinary system. The
      authors report a case of pseudoexstrophy with scaphoid megalourethra, and
      anorectal malformation. Kidneys and ureters were normal. Preliminary surgery
      consisted of a divided high sigmoid colostomy. The rare combination of
      pseudoexstrophy and megalourethra is discussed.

PMID- 12194151
TI  - Ergonomics: OSHA to develop industry guidelines by late 2002; VA resources
      online.

PMID- 12194150
TI  - Rare mesenchymal lesions: Hamartoma of the chest wall and juvenile active
      ossifying fibroma in siblings.
AB  - Mesenchymal hamartomas of the thorax are known as rare dysontogenetic tumorous
      non-neoplastic lesions. The juvenile active ossifying fibroma (JAOF) also is
      considered as a benign tumor like lesion of the mesenchymal connective tissue.
      The authors report the cases of 2 siblings-a 2-year-old girl with a hamartoma of
      the chest wall and her 4-year-old brother with a JAOF. The girl had bilocular
      mesenchymal hamartoma in the area of the 8(th) rib diagnosed in the first year of
      life, which was surgically removed completely. Her brother had been treated for
      JAOF of the right nasal sinus area diagnosed at the age of 15 months. Both
      lesions are extremely rare mutations of the local tissue, which occur typically
      in early childhood and continue benignly after surgical resection, but such a
      familial occurrence in siblings has not yet been reported. Furthermore, according
      to the histologic findings, the JAOF also could be seen as a hamartomatous
      lesion.

PMID- 12194152
TI  - NIOSH tips on protecting buildings from terrorists agents.

PMID- 12194153
TI  - My brilliant career--mental health manager. Northern lights. Interview by Ann
      Dix.

PMID- 12194154
TI  - Characterization of spirometric function in residents of three comparison
      communities and of three communities located near waste incinerators in North
      Carolina.
AB  - Waste incinerators are an increasingly common means of solid waste disposal.
      However, little is documented about the physical health of community members who
      live close to incinerators. During a 3-yr epidemiological study, spirometric lung
      function was tested once annually among residents from 3 communities surrounding
      a hazardous waste, biomedical, or municipal incinerator and among residents in 3
      comparison communities. A total of 1,016 nonsmoking individuals, aged 8-80 yr,
      participated during at least 1 of the 3 yr of the study; 358 individuals
      participated all 3 yr. Daily air-quality sampling was done for 1 mo/yr in all 6
      communities. The average monthly concentrations of particulate matter with
      diameters of 2.5 microns and less (PM2.5 [range = 14.6-31.5 micrograms/m3]) in
      all communities were similar during the 3 yr of study. The mean daily PM2.5
      concentrations were significantly less than the U.S. Environmental Protection
      Agency's allowable 24-hr standard of 65 micrograms/m3. Individual incinerators
      contributed less than 2.5% of the areas' total PM2.5 levels. There was no
      difference in percent predicted forced vital capacity, forced expiratory volume
      in 1 sec, or forced expiratory flow rate over the middle 50% of the forced vital
      capacity among members of the incinerator communities, compared with
      nonincinerator communities, and there were no significant differences in lung
      function within the 3 sets of communities. There was no evidence from this study
      that an association existed between residence in these 3 waste incinerator areas,
      which met state and federal emissions regulations, and average spirometric
      pulmonary function of nonsmoking community members.

PMID- 12194155
TI  - Is neurotoxicity associated with environmental trichloroethylene (TCE)?
AB  - Individuals who lived near 2 electronic manufacturing plants were exposed to
      odorous chlorinated solvents by inhalation (directly) and by out gassing from
      well water. An exposure zone was defined by concentrations of trichloroethylene,
      1,1,1-trichloroethane, tetrachloroethylene, and vinyl chloride in groundwater.
      The author adopted trichloroethylene as a "shorthand" for the exposure
      designation. Residents complained of impaired recall and concentration, and of
      dizziness; therefore, the focus of this investigation was brain functions.
      Neurobehavioral functions, Profile of Mood States, frequencies of 35 symptoms,
      and questionnaire responses provided by 236 residents from exposure zones were
      compared with responses provided by 161 unexposed regional referents and by 67
      Phoenix residents who lived outside the exposure zone areas. Pulmonary functions
      were measured with spirometry. Residents of the exposure zones were compared with
      regional referents, and the former had significantly (p < .05) delayed simple and
      choice reaction times, impaired balance, delayed blink reflex latency R-1, and
      abnormal color discrimination. In addition, these individuals had impaired (1)
      cognitive functions, (2) attention and perceptual motor speed, and (3) recall.
      Individuals who lived in exposure zones had airway obstructions. Adverse mood
      state scores and frequencies of 33 of 35 symptoms were elevated. In conclusion,
      individuals who lived in the exposure zones had neurobehavioral impairments,
      reduced pulmonary functions, elevated Profile of Mood State scores, and excessive
      symptom frequencies.

PMID- 12194156
TI  - Do duration of exposure, proximity to electronic manufacturing plants, and
      involvement in a lawsuit affect chlorinated solvent toxicity?
AB  - The author examined the effects of duration of residence, proximity to microchip
      plants, and being a party in litigation involving neurobehavioral functioning in
      individuals who had been chronically exposed to trichloroethylene-associated
      solvents from the environment. The author compared duration of exposure for the
      236 residents, all of whom were located in 3 proximity zones in Phoenix, Arizona;
      some of the individuals had been in the process of solvent-related litigation for
      fewer than 10 yr, whereas some had been involved for more than 10 yr. The 236
      residents were compared with 58 nonclaimants in 3 residential areas within the
      exposure zones. Neurobehavioral function testing was described in the study that
      appears prior to this study in this issue. Prior to comparisons, test scores were
      adjusted for age, sex, education level, and other significant factors.
      Individuals who had been exposed for fewer than 10 yr were not different from
      individuals who had been exposed for longer periods. Proximity to microchip
      plants produced no statistically significant effects. Among the 169 exposed
      subjects (i.e., exposure for 15 yr to trichloroethylene-associated solvents), of
      whom some were parties in lawsuits, those who lived in the near west area (Zone
      A) of Phoenix did not differ with respect to results of the 14 neurobehavioral
      tests that were administered. However, Zone B subjects, located to the north of
      the plant, differed with respect to 2 of the tests; and Zone C subjects, located
      beyond Zone A, Phoenix, differed with respect to 3 of the tests. In conclusion,
      duration of residence, proximity to microchip plants, and being a party to a
      lawsuit had no significant effects on neurobehavioral functioning, but, in this
      study, parties in the lawsuit were subjects who experienced more frequent
      symptoms.

PMID- 12194157
TI  - Neuropathy in an artist exposed to organic solvents in paints: a case study.
AB  - A 61-year-old artist in Israel had been painting for 30 years in his home studio.
      He had been healthy until he reached the age of 59.5 years, at which time he
      began complaining of weakness and paresthesia in both hands and legs. He also
      complained that he had difficulty concentrating, and his memory was impaired. His
      work was unusual in that he painted large posters (i.e., 2 x 3 m) with different
      mixtures of organic solvents, including toluene, xylene, benzene, methyl ethyl
      ketone, toluene diisocyanate, acetone, and thinner. He did not use any protective
      gloves and did not wear a mask. He was evaluated with several methods and was
      diagnosed as having peripheral and central neuropathy, including ototoxic hearing
      loss as a result of long exposures to organic solvents. The authors were unable
      to find any similar case report in the literature.

PMID- 12194158
TI  - The Po River Delta (north Italy) indoor epidemiological study: effects of
      pollutant exposure on acute respiratory symptoms and respiratory function in
      adults.
AB  - The authors studied the effects of relatively low doses of nitrogen dioxide and
      respirable suspended particulate matter (i.e., < 2.5 mu) on acute respiratory
      symptoms and on peak expiratory flow in 383 adults (15-72 yr of age) who lived in
      the Po River Delta area, located near Venice. During 2 wk-1 wk in winter and 1 wk
      in summer--the authors monitored each participant's house to measure nitrogen
      dioxide (in parts per billion) and respirable suspended particulate
      (microgram/m3) concentration. Information on sex, age, height, weight, daily
      activity patterns, active and passive smoking, chronic respiratory diseases,
      daily peak expiratory flow, and presence of acute respiratory symptoms during the
      weeks monitoring occurred were also collected. Peak expiratory flow variation was
      studied as mean amplitude percentage (i.e., amplitude/mean) and percentage of
      diurnal variation (maximum/minimum). The exposure indices to nitrogen dioxide
      (nitrogen dioxide--index of exposure) and to respirable suspended particulate
      matter (respirable suspended particulate matter-index of exposure) were computed
      as the product of pollutant concentration and time of exposure. The authors
      considered indices as "low" or "high" on the basis of the median value. The
      median nitrogen dioxide was 20 ppb in winter and 14 ppb in summer; the highest
      nitrogen dioxide levels occurred in the kitchen in the winter (33 ppb) and summer
      (20 ppb). The median respirable suspended particulate matter was 68 micrograms/m3
      in winter and 45 micrograms/m3 in summer. Only in winter were there significant
      associations between bronchitic/asthmatic symptoms and "high" nitrogen dioxide
      and respirable suspended particulate matter indices. In subjects who did not
      smoke, a significant influence of the "high" respirable suspended particulate
      matter-index of exposure was also observed in summer. With respect to peak
      expiratory flow and its variability, respirable suspended particulate matter
      index of exposure was associated with an increase of both amplitude/mean and
      maximum/mean; however, with respect to the nitrogen dioxide--index of exposure,
      the association was significant only in subjects with chronic respiratory
      diseases (i.e., asthma and bronchitis). These relationships were significant only
      in winter. In conclusion, the results of the current study indicate that there is
      an association between relatively low doses of pollutants and acute respiratory
      symptoms and peak expiratory flow in adults.

PMID- 12194159
TI  - Visits to physicians after the oxygenation of gasoline in Philadelphia.
AB  - During the period between 1992 and 1997, there was an increase in levels of
      methyl tertiary butyl ether (MTBE) in gasoline in the Philadelphia, Pennsylvania,
      area. In this study, the authors analyzed billing records from clinical practices
      that were extensions of the University of Pennsylvania. The authors based their
      selections on the International Classification of Diseases-9 diagnostic codes,
      which were determined from (1) previous studies of methyl tertiary butyl ether
      conducted by the Centers for Disease Control; (2) respiratory symptoms, including
      asthma and wheezing; and (3) symptoms associated anecdotally with methyl tertiary
      butyl ether levels in gasoline. The authors normalized all data by the total
      number of office visits. The incidences of headache, throat irritation, allergic
      rhinitis, cough, nausea, dizziness, upper respiratory infections, wheezing,
      otitis media, skin rash, anxiety, insomnia, palpitations, generalized allergy,
      and malaise were increased during the period studied. Large increases occurred
      during the winters of 1993-1994 and 1994-1995 (during which there were high
      levels of MTBE), but not in the preceding summers (during which there were low
      levels of MTBE). This was especially true for asthma and wheezing. During the
      summers of 1995, 1996, and 1997, the incidences of the aforementioned symptoms
      increased greatly.

PMID- 12194160
TI  - Relationships between indoor environments and nasal inflammation in nursing
      personnel.
AB  - In this study, the authors sought to address the relationships between measured
      indoor environmental factors and nasal patency (i.e., minimum cross-sectional
      area) and volume and markers of nasal inflammation in nasal lavage fluid.
      Clinical data were obtained for 115 females who worked at 36 geriatric nursing
      departments. The indoor climates in the nursing departments were characterized by
      high room temperatures (median = 23 degrees C), low relative air humidities
      (median = 24%), and high air exchange rates indicated by low carbon dioxide
      levels (median = 570 ppm). Evidence of microbial amplification was observed in
      the ventilation unit in 3 of the departments. Decreased nasal patency was
      observed relative to microbial amplification in the ventilation units (minimum
      cross-sectional area 1 = 0.80 cm2 vs. 0.64 cm2, p = .003, minimum cross-sectional
      area 2 = 0.80 cm2 vs. 0.67 cm2, p = .02) and in relation to elevated indoor
      temperature (volume 1 = 3.46 cm3 vs. 3.22 cm3, p = .03). The authors concluded
      that the indoor environment may have affected the nasal mucosa of nursing
      personnel, thus causing nasal mucosal swelling. The results support the view that
      fungal contamination of air-supply ducts may be a source of microbial pollution,
      which can affect the nasal mucosa.

PMID- 12194161
TI  - Paraquat intoxication in Korea.
AB  - In this study, the authors explored acute paraquat intoxication and determined
      potential factors related to paraquat fatalities. During 1999, 154 patients with
      paraquat intoxication were admitted to the Institute of Pesticide Poisoning at
      the Soonchunhyang University Chunan Hospital. The authors assessed paraquat
      exposure by quantifying the amount of ingested paraquat and by semiquantitative
      assay of paraquat in urine. Outcomes of paraquat intoxication were categorized as
      recovery or death. Among all the patients, 139 (90.3%) were transferred from
      other medical facilities to the Institute of Pesticide Poisoning following a mean
      exposure time of 20.1 hr (standard deviation = 2.6 hr). Intentional ingestion of
      paraquat accounted for 73.4% (113/154 patients) of all paraquat poisonings, and
      it represented a significantly higher fatality rate (53.2%) than did accidental
      ingestion (19.1% [p < .001]). The overall paraquat fatality was 43.8%. Multiple
      logistic-regression analysis revealed that the risk of fatality increased
      significantly with (1) the quantity of paraquat ingested and (2) a positive
      urinary paraquat test. The results indicated that paraquat is potentially lethal
      in humans, and the risk of fatality is directly related to the amount ingested
      and absorbed.

PMID- 12194162
TI  - Sleep disorders and daytime sleepiness in state police shiftworkers.
AB  - Police, who work shifts, participate in both risky and delicate tasks. The
      authors investigated sleep habits, prevalence of sleep disorders, sleepiness on
      the job, and hypnotic drug intake (Benzodiazepines, Zaleplon, Zolpidem, or
      Zoplicone) in a population of Italian state police officers. This study was
      conducted with self-administered questionnaires. The investigation focused on the
      difference between 540 non-shiftworkers (413 males, 127 females) and 575
      shiftworkers (483 males, 92 females). All individuals were between 20 yr and 39
      yr of age. In shiftworkers, there was a higher prevalence of difficulty in
      initiating sleep; in addition, these individuals had a sleep latency that
      exceeded 20 min, and they experienced early awakenings. No significant
      differences in daytime sleepiness and drug intake existed between the 2 groups.
      Self-evaluation of the number of hours that individuals slept each night and
      during a 24-hr period revealed that shiftworkers required more sleep. The results
      indicated that shiftworkers experienced a lower quality of sleep than non
      shiftworkers, but the former did not report increased daytime sleepiness or
      increased hypnotic drug intake (i.e., Benzodiazepines, Zaleplon, Zolpidem, or
      Zoplicone). Shiftworkers seemed to compensate for the poor quality of their sleep
      by sleeping for a greater number of hours during 24-hr periods than the non
      shiftworkers. Perhaps the aforementioned compensation resulted from a prolonged
      recovery from shiftwork effects.

PMID- 12194163
TI  - Suspected chronic organochlorine pesticide poisoning.

PMID- 12194164
TI  - Cancer in the semiconductor industry.

PMID- 12194165
TI  - Nephrotoxic actions of low-dose mercury in mice: protection by zinc.
AB  - The authors conducted this study to determine if very-low-dose (i.e., 4 ppm)
      mercury is nephrotoxic and, if so, whether the nephrotoxic actions of mercury in
      mice could be prevented by zinc intake. Animals were administered 4 ppm mercuric
      chloride and/or 800 ppm zinc chloride in their drinking water for 12 wk. The
      animals were sacrificed at the end of the exposure period, and their kidneys were
      excised, weighed, and processed for histological study. Both metals reduced
      significantly (p < .05) the absolute and relative kidney weights of the animals.
      Zinc-treated animals showed normal kidney histology that was comparable with that
      of the control. Mercury treatment produced necrosis and widening of the
      glomeruli, whereas a combination of both metals resulted in protection from the
      toxic effects, with most nephrons resembling the control. The results indicate
      that low-dose mercury exposure in mice kidney induces some degenerative effects,
      which are prevented by zinc.

PMID- 12194166
TI  - From the Centers for Disease Control. Staphylococcus aureus resistant to
      vancomycin--United States, 2002.

PMID- 12194167
TI  - From the Centers for Disease Control. Infant mortality and low birth weight among
      black infants--United States, 1980-2000.

PMID- 12194168
TI  - JAMA patient page. Hormone replacement therapy.

PMID- 12194169
TI  - [The life of Dr. John William Heron, the second superintendent of Chejungwon].
AB  - The purpose of this paper is to overview the life of John W. Heron, M. D. who was
      the first appointed medical missionary to Korea by the Presbyterian Church USA.
      Although he was a competent doctor as well as a devoted missionary, he is not
      well-known yet, because he died early after 5 years' service in Korea. Dr. Heron
      was born in Derbyshire, England on June 15, 1856. His father, Rev. E. S. Heron,
      was a Scotch Minister of Congregational Church. His family emigrated to America
      in 1870 when he was fourteen years old and settled in Knoxville, Tennessee. In
      1881, he was admitted to the University of Tennessee Medical School and graduated
      with highest honors in 1883. After training in New York University Hospital, he
      refused the offer of professorship from the University of Tennessee to become a
      medical missionary to Korea. He arrived in Seoul on June 21, 1885 and began to
      work in Royal Government Hospital, Chejungwon, the predecessor of Severance
      Hospital. In 1887, he became the superintendent of the Hospital following Dr.
      Horace N. Allen. He also worked for the Royal family and sometimes traveled to
      the rural areas to care for the patients. He started Chejungwon Church which
      later became Namdaemoon Presbyterian Church. In 1887, Dr. Heron worked as a
      member of the Bible translation committee and in 1889, he was elected as the
      chairman of the Public Committee of the Presbyterian Churches. In 1890, he
      established 'The Korean Religious Tract Society (Chosunsyungkyoseohoi) with
      Underwood and Ohlinger. The society published and replenished Christian books,
      periodical magazines and booklets. In the Summer of 1890, Dr. Heron did his best
      to take care of the sick suffering from an epidemic dysentery and himself got
      infected because of the terrible overwork. He passed away on July 26th, 1890. On
      his deathbed, he told his soldier and native friends around him as follow: "Jesus
      loves you. He gave His life for you. Stand by Him!" The martyrdom of Dr. Heron
      should be remembered in the Korean history of mission, because he was the first
      victim among the foreign missionaries who had lived and worked in Seoul for
      Korean mission. Dr. Heron's mind of love, service and devotion should be
      remembered by the medical doctors working today in caring for the patients
      suffering from physical and spiritual illnesses.

PMID- 12194170
TI  - [The policy of the United States Army Military Government in Korea toward public
      health and medicine in occupied South Korea].
AB  - After the liberation from Japanese colonial rule in August 1945, the United
      States of America established Military Government in Korea(USAMGIK) south the
      38th parallel. The public health and medical policy of the USAMGIK was defined by
      the USA's general policy toward Korea, and followed national interests of USA
      after the end of the World War II. The basic objectives of the early occupational
      period were two; the protection of the occupation troops, the prevention of acute
      epidemic diseases and unrest in the populace. However, after the switch of
      occupation policy to the establishment of pro-American anti-Communist nation in
      Korea since June 1946, the basic objectives turned into 'the establishment of the
      influence of American medicine in Korean medical system.' During the occupation
      period, USAMGIK trained several pro-American right - wing doctors who formed the
      clique of policy makers in the independent government, and established many quasi
      - American public health and medical systems in Korea.

PMID- 12194171
TI  - [Richard Wunsch].

PMID- 12194172
TI  - The Tom channel in the mitochondrial outer membrane: alive and kicking.
AB  - The targeting of newly-made polypeptides to specific membranes, and the
      subsequent ability of a membrane to allow only certain polypeptides into its
      compartment, are essential to maintain the ultrastructure of Eukaryotic cells.
      Distinct oligomeric protein complexes in each cellular membrane catalyse these
      translocation processes. A recent report [Hill K et al. Nature 1998;395:516-521
      (Ref. 1)] of the reconstitution of the translocation channel from the
      mitochondrial outer membrane, after producing the major structural component of
      the channel by recombinant means, promises a system to dissect in molecular
      detail the exact working of one of these protein translocation machines.

PMID- 12194173
TI  - Registration and reregistration application fees. Confirmation of final rule,
      remanded for further notice and comment, and response to comments.
AB  - DEA is publishing a final rule regarding the registration and reregistration fees
      charged to controlled substances registrants. DEA is required to charge
      reasonable fees relating to the registration and control of the manufacture,
      distribution, and dispensing of controlled substances. To address this mandate,
      on March 22, 1993 DEA published a final rule in the Federal Register,
      establishing registration fees for controlled substances registrants (58 FR
      15272). Following publication of the final rule, the American Medical Association
      (AMA) and others filed a complaint in the United States District Court for the
      District of Columbia objecting to the new fees. The district court issued its
      final order granting the government's motion for summary judgment and disposing
      of all claims. The AMA appealed. The United States Court of Appeals for the
      District of Columbia Circuit found DEA's rulemaking to be inadequate. The appeals
      court remanded, without vacating, the rule to DEA, requiring the agency to
      provide an opportunity for meaningful notice and comment on the fee-funded
      components of the Diversion Control Program. DEA responded to the remand
      requirement through a document published in the Federal Register on December 30,
      1996 (61 FR 68624). This Final Rule supplements the December 30, 1996 Federal
      Register document and with that document, constitutes the final rule on the Drug
      Diversion Control Fee Account.

PMID- 12194174
TI  - Many courts still Frye scientific evidence.

PMID- 12194175
TI  - Supplementing antiretroviral therapy.

PMID- 12194176
TI  - Alternative HIV vaccine strategies.

PMID- 12194177
TI  - Envelope-based HIV vaccines.

PMID- 12194178
TI  - A wireless, remote query ammonia sensor.
AB  - This paper presents a wireless, remote query ammonia sensor comprised of a free
      standing magnetoelastic thick-film coated with a polymer, poly(acrylic acid-co
      isooctylacrylate), that changes mass in response to atmospheric ammonia
      concentration. The mass of the polymer layer modulates the resonant frequency the
      ferromagnetic magnetoelastic substrate, hence by monitoring the frequency
      response of the sensor, atmospheric NH3 concentration can be determined remotely,
      without the need for physical connections to the sensor or specific alignment
      requirements. The effect of copolymer composition, polymer film thickness, and
      relative humidity level (RH) on the sensitivity of the sensor were investigated.
      The sensor linearly tracks ammonia concentration below 0.8 vol.%, and tracks
      higher concentrations logarithmically; within the linear calibration range, a
      0.02 vol.% change in NH3 concentration can be detected.

PMID- 12194179
TI  - Efficient dynamic constraints for animating articulated figures.
AB  - This paper presents an efficient dynamics-based computer animation system for
      simulating and controlling the motion of articulated figures. A non-trivial
      extension of Featherstone's O(n) recursive forward dynamics algorithm is derived
      which allows enforcing one or more constraints on the animated figures. We
      demonstrate how the constraint force evaluation algorithm we have developed makes
      it possible to simulate collisions between articulated figures, to compute the
      results of impulsive forces, to enforce joint limits, to model closed kinematic
      loops, and to robustly control motion at interactive rates. Particular care has
      been taken to make the algorithm not only fast, but also easy to implement and
      use. To better illustrate how the constraint force evaluation algorithm works, we
      provide pseudocode for its major components. Additionally, we analyze its
      computational complexity and finally we present examples demonstrating how our
      system has been used to generate interactive, physically correct complex motion
      with small user effort.

PMID- 12194180
TI  - An all-silicon single-wafer micro-g accelerometer with a combined surface and
      bulk micromachining process.
AB  - This paper reports an all-silicon fully symmetrical z-axis micro-g accelerometer
      that is fabricated on a single-silicon wafer using a combined surface and bulk
      fabrication process. The microaccelerometer has high device sensitivity, low
      noise, and low/controllable damping that are the key factors for attaining micro
      g and sub-micro g resolution in capacitive accelerometers. The microfabrication
      process produces a large proof mass by using the whole wafer thickness and a
      large sense capacitance by utilizing a thin sacrificial layer. The sense/feedback
      electrodes are formed by a deposited 2-3 microns polysilicon film with embedded
      25-35 microns-thick vertical stiffeners. These electrodes, while thin, are made
      very stiff by the thick embedded stiffeners so that force rebalancing of the
      proof mass becomes possible. The polysilicon electrodes are patterned to create
      damping holes. The microaccelerometers are batch-fabricated, packaged, and tested
      successfully. A device with a 2-mm x 1-mm proof mass and a full bridge support
      has a measured sensitivity of 2 pF/g. The measured sensitivity of a 4-mm x 1-mm
      accelerometer with a cantilever support is 19.4 pF/g. The calculated noise floor
      of these devices at atmosphere are 0.23 micro g/sqrt(Hz) and 0.16 micro
      g/sqrt(Hz), respectively.

PMID- 12194181
TI  - Viscoelastic flow modeling in the extrusion of a dough-like fluid.
AB  - This work attempts to investigate the effect of viscoelasticity and three
      dimensional geometry in screw channels. The Phan-Thien Tanner (PTT) constitutive
      equation with simplified model parameters was solved in conjunction with the flow
      equations. Polyflow, a commercially available finite element code was used to
      solve the resulting nonlinear partial differential equations. The PTT model
      predicted one log scale lower pressure buildup compared to the equivalent
      Newtonian results. However, the velocity profile did not show significant changes
      for the chosen PTT model parameters. Past Researchers neglected viscoelastic
      effects and also the three dimensional nature of the flow in extruder channels.
      The results of this paper provide a starting point for further simulations using
      more realistic model parameters, which may enable the food engineer to more
      accurately scale-up and design extrusion processes.

PMID- 12194182
TI  - Signal transduction mechanisms in plants: an overview.
AB  - This article provides an overview on recent advances in some of the basic
      signalling mechanisms that participate in a wide variety of stimulus-response
      pathways. The mechanisms include calcium-based signalling, G-protein-mediated
      signalling and signalling involving inositol phospholipids, with discussion on
      the role of protein kinases and phosphatases interspersed. As a further defining
      feature, the article highlights recent exciting findings on three extracellular
      components that have not been given coverage in previous reviews of signal
      transduction in plants, extracellular calmodulin, extracellular ATP, and integrin
      like receptors, all of which affect plant growth and development.

PMID- 12194183
TI  - Approach and issues relating to shield material design to protect astronauts from
      space radiation.
AB  - One major obstacle to human space exploration is the possible limitations imposed
      by the adverse effects of long-term exposure to the space environment. Even
      before human spaceflight began, the potentially brief exposure of astronauts to
      the very intense random solar energetic particle (SEP) events was of great
      concern. A new challenge appears in deep space exploration from exposure to the
      low-intensity heavy-ion flux of the galactic cosmic rays (GCR) since the missions
      are of long duration and the accumulated exposures can be high. Since aluminum
      (traditionally used in spacecraft to avoid potential radiation risks) leads to
      prohibitively expensive mission launch costs, alternative materials need to be
      explored. An overview of the materials related issues and their impact on human
      space exploration will be given.

PMID- 12194184
TI  - Relative effectiveness of kinetic analysis vs single point readings for
      classifying environmental samples based on community-level physiological profiles
      (CLPP).
AB  - The relative effectiveness of average-well-color-development-normalized single
      point absorbance readings (AWCD) vs the kinetic parameters mu(m), lambda, A, and
      integral (AREA) of the modified Gompertz equation fit to the color development
      curve resulting from reduction of a redox sensitive dye from microbial
      respiration of 95 separate sole carbon sources in microplate wells was compared
      for a dilution series of rhizosphere samples from hydroponically grown wheat and
      potato ranging in inoculum densities of 1 x 10(4)-4 x 10(6) cells ml-1. Patterns
      generated with each parameter were analyzed using principal component analysis
      (PCA) and discriminant function analysis (DFA) to test relative resolving power.
      Samples of equivalent cell density (undiluted samples) were correctly classified
      by rhizosphere type for all parameters based on DFA analysis of the first five PC
      scores. Analysis of undiluted and 1:4 diluted samples resulted in
      misclassification of at least two of the wheat samples for all parameters except
      the AWCD normalized (0.50 abs. units) data, and analysis of undiluted, 1:4, and
      1:16 diluted samples resulted in misclassification for all parameter types.
      Ordination of samples along the first principal component (PC) was correlated to
      inoculum density in analyses performed on all of the kinetic parameters, but no
      such influence was seen for AWCD-derived results. The carbon sources responsible
      for classification differed among the variable types with the exception of AREA
      and A, which were strongly correlated. These results indicate that the use of
      kinetic parameters for pattern analysis in CLPP may provide some additional
      information, but only if the influence of inoculum density is carefully
      considered.

PMID- 12194185
TI  - Clypeatula cooperensis gen. n., sp. n., a new freshwater sponge (Porifera,
      Spongillidae) from the Rocky Mountains of Montana, USA.
AB  - A new genus and species of freshwater sponge, Clypeatula cooperensis, collected
      from three lakes in the Northern Rocky Mountains of Montana, USA, are described.
      The sponge grows as a hard, disc-shaped encrustation on the undersides of rocks
      and logs. It lacks microscleres and has amphioxeal megascleres that often show a
      slight midregion bulb and are usually covered with short, conical spines except
      at their tips. The sponge is also non-gemmulating, overwintering in a regressed
      state in which choanocyte chambers are reduced in number. Phylogenetic analyses
      of complete 18S rDNA sequences of C. cooperensis, Ephydatia muelleri, Spongilla
      lacustris and Eunapius fragilis suggest that C. cooperensis is more closely
      related to Ephydatia muelleri than to Spongilla lacustris or Eunapius fragilis.
      Our data, nonetheless, do not rule out the possibility that C. cooperensis is
      more closely related to the non-gemmulating sponges of Lake Baikal (Russia) than
      it is to Ephydatia muelleri. These phylogenetic analyses support the erection of
      a new genus, the monophyly of freshwater sponges belonging to the families
      Spongillidae and Lubomirskiidae, and the monophyly of demosponges.

PMID- 12194186
TI  - Comparison of observed rheological properties of hard wheat flour dough with
      predictions of the Giesekus-Leonov, White-Metzner and Phan-Thien Tanner models.
AB  - The measured rheological behavior of hard wheat flour dough was predicted using
      three nonlinear differential viscoelastic models. The Phan-Thien Tanner model
      gave good zero shear viscosity prediction, but overpredicted the shear viscosity
      at higher shear rates and the transient and extensional properties. The Giesekus
      Leonov model gave similar predictions to the Phan-Thien Tanner model, but the
      extensional viscosity prediction showed extension thickening. Using high values
      of the mobility factor, extension thinning behavior was observed but the
      predictions were not satisfactory. The White-Metzner model gave good predictions
      of the steady shear viscosity and the first normal stress coefficient but it was
      unable to predict the uniaxial extensional viscosity as it exhibited asymptotic
      behavior in the tested extensional rates. It also predicted the transient shear
      properties with moderate accuracy in the transient phase, but very well at higher
      times, compared to the Phan-Thien Tanner model and the Giesekus-Leonov model.
      None of the models predicted all observed data consistently well. Overall the
      White-Metzner model appeared to make the best predictions of all the observed
      data.

PMID- 12194187
TI  - Modelling the firing pattern of bullfrog vestibular neurons responding to
      naturalistic stimuli.
AB  - We have developed a neural system identification method for fitting models to
      stimulus-response data, where the response is a spike train. The method involves
      using a general nonlinear optimisation procedure to fit models in the time
      domain. We have applied the method to model bullfrog semicircular canal afferent
      neuron responses during naturalistic, broad-band head rotations. These neurons
      respond in diverse ways, but a simple four parameter class of models elegantly
      accounts for the various types of responses observed.

PMID- 12194188
TI  - State-space receptive fields of semicircular canal afferent neurons in the
      bullfrog.
AB  - Receptive fields are commonly used to describe spatial characteristics of sensory
      neuron responses. They can be extended to characterize temporal or dynamical
      aspects by mapping neural responses in dynamical state spaces. The state-space
      receptive field of a neuron is the probability distribution of the dynamical
      state of the stimulus-generating system conditioned upon the occurrence of a
      spike. We have computed state-space receptive fields for semicircular canal
      afferent neurons in the bullfrog (Rana catesbeiana). We recorded spike times
      during broad-band Gaussian noise rotational velocity stimuli, computed the
      frequency distribution of head states at spike times, and normalized these to
      obtain conditional pdfs for the state. These state-space receptive fields
      quantify what the brain can deduce about the dynamical state of the head when a
      single spike arrives from the periphery.

PMID- 12194189
TI  - Ethics: virtue and politics in the science and practice of psychology.
AB  - The discipline of psychology is moving beyond the myth of detached neutrality to
      discover virtue and to recognize politics as forces which determine ethical
      behaviour. Humankind has struggled over the centuries to discover the nature of
      good and evil and to define the rightness and wrongness of human behaviour.
      Psychology has a short history in formalizing codes of ethics and codes of
      conduct. Current and historical events, concepts and values, including those
      based on philosophy and religion, have influenced the development of psychology's
      scientific and professional codes. The ethical behaviour of psychologists may be
      inspired by values, regulated by rules, determined by external pressures, or any
      combination of these. Emerging issues and challenges in today's changing and
      turbulent society require an incorporation of moral principles in finding
      acceptable strategies to achieve acceptable goals. May virtue and politics go
      hand in hand in creating a better world.

PMID- 12194190
TI  - Harmonization in the regulation of pharmaceutical research and human rights: the
      need to think globally.

PMID- 12194191
TI  - Alternative approaches to patient and family medical ethics: review and
      assessment.

PMID- 12194192
TI  - Learning ethics the hard way: facing the ethics committee.
AB  - This article describes an approach to enhancing the value of case study material
      in teaching professional ethics in psychology. The mock committee approach
      involves a series of hearings convened by students who rotate membership on a
      class ethics committee. Members of the class participate randomly as
      psychologists accused of various ethical violations. While the class observes,
      formal complaint hearings occur that result in official rulings and the setting
      of appropriate penalties and remedial requirements. The larger class then joins
      in active feedback and exchange with the committee to highlight and discuss
      salient ethical issues. We present and discuss student evaluation data for this
      technique and comment on the potential advantages of this teaching approach.

PMID- 12194193
TI  - Debate over whether to defend animal tests.

PMID- 12194194
TI  - The principle of cooperation.

PMID- 12194195
TI  - Genetics and ethics.

PMID- 12194196
TI  - Ethical issues in health care: should health care professionals unionize?

PMID- 12194197
TI  - Evaluation of human subject protections in schizophrenia research conducted by
      the University of ... (Part I).

PMID- 12194198
TI  - New York state laws on protection of human subjects conflict with each other.

PMID- 12194199
TI  - Chicken cells--oncogene transformation, immortalization and more.
AB  - Domestic chicken as a laboratory animal as well as chicken cells in vitro have
      been highly evaluated in several fields of experimental biology. Retrovirology
      and experimental oncology traditionally use this model, whose comparative aspects
      are still inspirative. The first (retro)viral aetiology of a tumour was
      recognized in the chicken and the first quantitative in vitro measurement of
      oncogenic transformation was developed using the chicken cells. Chicken cells
      (like human and primate, but unlike rodent cells) have a long primary life-span,
      during which they remain genetically stable. While this property is advantageous
      for several types of experiments, it correlates with a low propensity of the
      chicken cells to immortalization. Recent establishment of several continuous
      chicken cell lines, however, has surmounted this drawback. Furthermore, the
      chicken B cell line DT40 was proved to be extremely useful for gene disruption
      studies because of a high frequency of gene targeting not found in any vertebrate
      cells. In the present communication, we have tried to review several traditional
      achievements accomplished using the chicken model and point to newly opened
      areas, where chicken cells appear to be an efficient tool, particularly in cell
      transformation and immortalization.

PMID- 12194200
TI  - Chromosome assignment of Cd36 transgenes in two rat SHR lines by FISH and linkage
      mapping of transgenic insert in the SHR-TG19 line.
AB  - The chromosome position of the Cd36 insert was determined by FISH in two rat
      transgenic lines (SHR/Ola-TgN(EF1aCd36)10Ipcv (SHR-TG10) and SHR/Ola
      TgN(EF1aCd36)19Ipcv (SHR-TG19). The Cd36 transgene construct labelled with
      digoxigenin-11-dNTP was used as a probe in the FISH analysis. In accord with the
      previous finding that the SHR-TG10 harbours 6-8 copies of the transgene, the
      signals from both metaphase and interphase nuclei of SHR-TG10 preparations were
      rather strong and the probe hybridized to both copies of chromosome 1 at band
      q55. The probe hybridization to SHR-TG19 metaphase preparations also showed
      homozygosity of the transgene with localization of both copies to chromosome 11
      at band q11. The signals were distinct but much weaker compared to the SHR-TG10,
      which again is in accord with the fact that the SHR-TG19 line harbours only a
      single copy of the transgene. In order to look for a possible impact of the
      insertion site neighbourhood upon the transgene phenotypic effect, we performed
      linkage mapping of the transgene in the SHR-TG19 line. By linkage mapping, the
      placement of the transgene to the proximal part of RNO11 was confirmed, the
      critical interval being 4 cM between D11Rat20 and D11Rat21, in good agreement
      with the RH map. Within the close neighbourhood of the inserted Cd36 transgene,
      there are several genes known to be expressed in kidney, and so the influence of
      some regulatory sequences enhancing kidney expression of the Cd36 transgene can
      be envisaged.

PMID- 12194201
TI  - Influence of oviductal fluid on ovine embryo viability.
AB  - The severe loss of developmental competence affecting fertilized ova when removed
      from the oviductal environment suggests that this organ plays a functional role
      in early embryonic development. The purpose of this study was to determine the
      effect of sheep heat-inactivated OF on the mortality rate of ovine embryos
      produced in vitro and transferred into recipients. As control groups we used
      embryos fertilized and cultured in media supplemented with different kinds of
      proteins (FCS, BSA). Transfer of embryos in the two pronuclei stage to the
      oviducts of synchronized recipients resulted in 60% of successfully termed
      pregnancies after incubation of embryos in OF, 40% in BSA and only 10% after FCS.
      All ewes were further assessed for pregnancy by ultrasonography 33, 53 and 80
      days after embryo transfer. The highest embryo mortality appeared between day 33
      and 52. We concluded that incubation of ovine oocytes in OF during the final
      period of the maturation process may play a functional role at the time of
      fertilization and early embryonic development.

PMID- 12194202
TI  - The status of the chromatin of human preimplantation embryos with good
      morphology.
AB  - The data about the relation and succession of blastomere fragmentation, cleavage
      rate and chromatin anomalies in preimplantation mammalian embryos are empirical
      and controversial at present. In this work we studied the proportion of nuclear
      fragmentation and condensation in 3-5-cell stage human embryos with no or minimal
      blastomere fragmentation (morphological class A and B, respectively) and the
      possibilities to perform FISH chromosomal analyses with them. We observed
      different stages of chromatin damage in blastomere nuclei corresponding to the
      steps of nuclear apoptotic changes well known in many cell types. The ploidity
      analysis of chromosomes 1, 5, 19 and X was determined as successful in embryos
      which had at least 2 out of 3, 3 out of 4 or 3 out of 5 normal nuclei with an
      equal number of FISH signals. There was no difference in the percentage of
      abnormal nuclei among the A- and B-class embryos. Tendencies noted by us suggest
      that the minimal blastomere fragmentation (up to 20% of perivitelline space) does
      not preclude the normal nuclear status allowing successful ploidy testing. The
      presence of condensed chromatin is a critical factor for interphase cytogenetic
      analysis of single early blastomeres.

PMID- 12194203
TI  - Conditions for gene transfection into the HL-60 human leukaemia cell line by
      electroporation.
AB  - Electroporation represents a powerful technique for cell transfection; however,
      its efficiency in haemopoietic cells (approximately 1%) is largely
      unsatisfactory. Biological processes in haemopoietic cells are often studied
      using leukaemia cell line HL-60. For this reason we developed conditions for
      efficiently introducing plasmids to HL-60 cells by electroporation, as an
      alternative to other techniques. This technique employs the electric pulse (250
      270 V; 1000 microF) followed by separation of living cells on a Ficoll-Paque
      discontinuous gradient. Using 10-20 micrograms of plasmid, we routinely achieve
      12-14% of transfectants.

PMID- 12194204
TI  - Genetic determination of polyhydroxyalkanoate metabolism in Rhodobacter
      capsulatus SB1003.
AB  - A cluster of four genes was identified in the Rhodobacter capsulatus genome that
      is involved in PHA metabolism. These genes encode the PHA granule-associated
      protein (pha2), the regulator for granule formation (pha1), the PHA synthase
      (phaC) and the PHA depolymerase (orfX). Two other genes, namely those encoding
      beta-ketothiolase (phaA) and acetoacetyl-CoA reductase (phaB), are not linked to
      this cluster.

PMID- 12194205
TI  - Asymmetric vimentin distribution in human spermatozoa.
AB  - The subject of the study was vimentin distribution in spermatozoa from human
      ejaculates by immunofluorescence and immunogold electron microscopy. In
      accordance with earlier reports, vimentin was found in the sperm head and was
      localized mainly in the equatorial segment region. However, electron microscopic
      observations revealed an additional intriguing detail: vimentin-associated gold
      granules showed asymmetric distribution. This asymmetry tended to be more
      pronounced in heads with defects such as cytoplasmic droplets. Abnormal cells
      also had positive reaction for vimentin in the neck and the proximal midpiece,
      but in these domains gold granule distribution was apparently uniform. These
      findings seem to support the hypothesis that the surfaces of the mammalian sperm
      head are functionally non-equivalent, although morphological basis for such a
      phenomenon is evident only in rodents. It is also interesting that asymmetry in
      vimentin distribution correlates with distinct types of sperm structural defects.

PMID- 12194206
TI  - Direct visualization of abasic sites on a single DNA molecule using fluorescence
      microscopy.
AB  - A new method was developed to allow direct visualization of damaged sites on
      individual DNA molecules. Fluorescence in situ hybridization on extended DNA
      molecules was modified to detect a single abasic site. Abasic sites were
      specifically labeled with a biotinylated aldehyde-reactive probe and fluorochrome
      conjugated streptavidin. The light emitted by a single fluorochrome-DNA complex
      was calibrated. The number of abasic sites on the DNA molecule was estimated by
      counting each fluorochrome-DNA complex. The present study directly visualized and
      characterized the abasic sites of single DNA molecules.

PMID- 12194207
TI  - Do liposome-binding constants of porphyrins correlate with their measured and
      predicted partitioning between octanol and water?
AB  - We tested correlations between lipophilicity parameters and the partitioning of
      sensitizers into membranes. For this purpose we investigated 17 porphyrins and
      two chlorins having various chemical structures. Some of these compounds possess
      an amphiphilic structure (including hematoporphyrin, deuteroporphyrin,
      mesoporphyrin, chlorin e6 and more). The others are very symmetrical sensitizers
      [meso-tetra(N-methyl-4-pyridyl)porphyrin, tetra-benzoporphyrin, coproporphyrin I
      dihydrochloride (CP), meso-tetra(4-carboxyphenyl)porphyrin (TCP) and meso-tetra(m
      hydroxyphenyl)chlorin]. Our investigation also included two series of
      hematoporphyrins and protoporphyrins with varying lengths of alkylcarboxylate
      side groups. The partitioning of these compounds between the bulk aqueous phase
      and liposomes was studied by fluorescence methods, and a liposome-binding
      constant, Kb, was obtained. It was found that CP and TCP do not incorporate into
      the lipid phase at pH 7.3. An n-octanol-water partition coefficient (log P) and a
      distribution coefficient (log D) were predicted with a modeling software. The
      values of log D were also obtained experimentally. We found that for the studied
      molecules, the predicted log D correlated well with the measured values. The
      values of log D as well as log P, in turn, did not correlate nicely, for the
      whole group of studied compounds, with the binding constants to liposomes.
      However, in the case of porphyrins that share a similar structure, the Kb showed
      good linear correlation with both log P and log D. For the series of
      hematoporphyrins and protoporphyrins with different lengths of alkylcarboxyl
      groups, it was shown that prolongation of this group caused an increase in the
      lipophilicity and the liposome-binding constant. This effect is more pronounced
      for the proto- than for the hematoporphyrin series. The results highlight the
      possible use, as well as limitations, of lipophilicity parameters for the
      prediction of membrane binding.

PMID- 12194209
TI  - Photodynamics of the bacteriochlorophyll-carotenoid system. 2. Influence of
      central metal, solvent and beta-carotene on photobleaching of bacteriochlorophyll
      derivatives.
AB  - Bacteriochlorophyll (BChl) derivatives (with central Mg replaced by metal "M")
      ([M]-BChl with M = 2H, Mg, Zn, Pd, Cu) have been investigated for their
      photodynamic capacity and stability toward photodegradation in organic solvents
      and aqueous micellar solution. A protocol has been developed for screening new
      sensitizers. BChl and [Zn]-BChl are efficient sensitizers, but they are also
      quickly degraded by the reactive oxygen species (ROS) produced by
      autosensitization, as well as by hetero-sensitization with 17(4)-methyl-13(2)
      demethoxycarbonyl-pheophorbide a (MPP). Photostable [Cu]-BChl is a poor
      sensitizer, whereas [Pd]-BChl and bacteriopheophytin a are not only very
      efficient sensitizers but are also very stable toward ROS. beta-Carotene is no
      efficient physical quencher of ROS in the system; rather, it acts as a
      photochemical quencher that competes with [M]-BChl and undergoes photooxygenation
      at high rates. Photolability seems to depend on the pigment oxidation potential
      and, in parallel, on the presence of central metals preferring coordination
      numbers higher than 4, whereas photodynamic capacity depends on long excited
      state life-times of the pigment or efficient intersystem crossing (or both).

PMID- 12194208
TI  - New photoactivators for multiphoton excited three-dimensional submicron cross
      linking of proteins: bovine serum albumin and type 1 collagen.
AB  - We report the synthesis and optical characterization of two new photoactivators
      and demonstrate their use for multiphoton excited three-dimensional free-form
      fabrication with proteins. These reagents were developed with the goal of cross
      linking Type 1 collagen. This cross-linking process produces structures on the
      micron and submicron size scales. A rose bengal diisopropyl amine derivative
      combines the classic photoactivator and co-initiator system into one molecule,
      reducing the reaction kinetics and increasing cross-linking efficiency. This
      derivative was successful at producing stable structures from collagen, whereas
      rose bengal alone was not effective. A benzophenone dimer connected by a flexible
      diamine tether was also synthesized. This activator has two photochemically
      reactive groups and is highly efficient in cross-linking bovine serum albumin and
      Type 1 collagen to form stable, robust structures. This approach is more flexible
      in terms of cross-linking a variety of proteins than by traditional benzophenone
      photochemistry. The photophysical properties vary greatly from that of
      benzophenone, with the appearance of a new, lower energy absorption band (lambda
      max approximately 370 nm in water) and broad, visible emission band
      (approximately 500 nm maximum). This absorption band is highly solvatochromic,
      suggesting it arises, at least in part, from a charge transfer interaction.
      Collagens are typically difficult to cross-link photochemically, and the results
      here suggest that these two new activators will be suitable for cross-linking
      other forms of collagen and additional proteins for biomedical applications such
      as the de novo assembly of biomimetic tissue scaffolds.

PMID- 12194210
TI  - Toward the molecular flashlight: preparation, properties, and photophysics of a
      hypericin-luciferin tethered molecule.
AB  - The synthesis of a molecule containing hypericin and luciferin moieties joined by
      a tether is reported. The light-induced (in vitro) antiviral activity as well as
      the photophysical properties of this new compound are measured and compared with
      those of the parent compounds, hypericin and pseudohypericin. This tethered
      molecule exhibits excited-state behavior that is very similar to that of its
      parent compounds and antiviral activity that is identical, within experimental
      error, to that of its more closely related parent compound, pseudohypericin. The
      implications for a photodynamic therapy that is independent of external light
      sources are discussed.

PMID- 12194212
TI  - Biological effects of polychromatic light.
AB  - Predicting the effects of polychromatic light on biological systems is a central
      goal of environmental photobiology. If the dose-response function for a process
      is a linear function of the light incident on a system at each wavelength within
      the spectrum, the effect of a polychromatic spectrum is obtained by integrating
      the product of the cross section for the reaction at each wavelength and the
      spectral irradiance at that wavelength over both wavelength and time. This
      procedure cannot be used, however, if the dose-response functions for an effect
      are not linear functions of photon dose. Although many photochemical reactions
      are linear within the biologically relevant range of doses, many biological end
      points are not. I describe procedures for calculating the effects of
      polychromatic irradiations on systems that exhibit certain classes of dose
      response functions, including power law responses typical of mutation induction
      and exponential dose-responses typical of cell survival. I also present an
      approach to predict the effects of polychromatic spectra on systems in which the
      ultraviolet components form pyrimidine dimers, and the longer-wavelength
      ultraviolet and visible components remove them by photoreactivation, thus
      generating complex dose-response functions for these coupled light-driven
      reactions.

PMID- 12194213
TI  - Daily doses of biologically active UV radiation retrieved from commonly available
      parameters.
AB  - A multiple linear correlation is done between atmospheric transmissivity for four
      biologically active radiation daily doses (UVB, erythemal, DNA and plant damage)
      T, and three parameters (daily sunshine fraction sigma, cosine of the daily
      minimum solar zenith angle mu min and daily total ozone column omega). T is
      defined as the ratio of a daily dose to its extra-atmospheric value. The data
      used are spectral UV measurements (390-400 nm at 0.5 nm step) recorded along year
      2000 and over 8 months of year 2001 at Briancon Station (Alps, 1300 m above sea
      level) that forms part of the French UV network. The coefficients obtained from
      year 2000 correlation permit to retrieve daily doses for year 2001 with an
      average error running from 3 to 9% for monthly mean values and from 2 to 4.5% for
      3-monthly mean values, depending on daily dose type. The retrieval of yearly mean
      value gives an error between 4 and 7.5%. Retrieving the daily dose of a given
      day, where sigma > or = 0.2, introduces error running from 16 to 32% depending on
      daily dose. An attempt to retrieve the yearly mean UVB daily dose for a northern
      France site, from the previous coefficients, gives encouraging results.

PMID- 12194214
TI  - Photofragmentation of dichloromethanol Cl2CHOH along C-O and C-Cl cleavages: a
      theoretical study.
AB  - Multireference configuration interaction calculations are carried out for ground
      and excited states of dichloromethanol, Cl2CHOH, to investigate two important
      photofragmentation processes relevant to atmospheric chemistry. Five low-lying
      excited states (1(1)A", 2(1)A', 1(3)A", 2(3)A" and 1(3)A') in the energy range
      between 6.4 and 7.5 eV are found to be highly repulsive for C-Cl elongation,
      leading to ClCHOH (X2A) and Cl (X2P). Photodissociation along the C-O bond
      resulting in CHCl2 (X2A') and OH (X2II) has to overcome a barrier of about 0.5 eV
      because the low-lying excited states 1(1)A", 1(3)A' and 1(3)A" become repulsive
      only after the C-O bond is elongated by about 0.3 A.

PMID- 12194211
TI  - An outdoor multiple wavelength system for the irradiation of biological samples:
      analysis of the long-term performance of various lamp and filter combinations.
AB  - A polychromatic irradiation system for the outdoor exposure of plants or other
      samples to additional UV and longer-wavelength radiation has been constructed and
      tested. The system provides a range of wavebands in the ultraviolet-B radiation
      (280-315 nm) and ultraviolet-A radiation (315-400 nm) spectral regions, and the
      irradiance is fully adjustable. The performance of the lamp and filter system
      after over 4000 h of use is described; a brief description of filter degradation
      after over 30,000 h of use is also presented. Cellulose acetate filters were
      found to be adequate for some purposes in the UV waveband, but rigid plastic and
      glass-based filters were superior in terms of stability and the range of spectral
      combinations available. They also exhibited relatively small changes in
      transmittance with time. The system is also convenient for the measurement of
      differential polychromatic action spectra.

PMID- 12194215
TI  - UV index experimental values during the years 2000 and 2001 from the Spanish
      broadband UV-B radiometric network.
AB  - An analysis is made of experimental ultraviolet erythemal solar radiation data
      measured during the years 2000 and 2001 by the Spanish UV-B radiation evaluation
      and prediction network. This network consists of 16 Robertson-Berger type
      pyranometers for evaluating solar erythemal radiation and five Brewer
      spectroradiometers for evaluating the stratospheric ozone. On the basis of these
      data the Ultraviolet Index (UVI) was evaluated for the measuring stations that
      are located either in coastal regions or in the more densely populated regions
      inland on the Iberian Peninsula. It has been checked that in most cases the
      maximum irradiance values corresponded to solar noon, although there were
      exceptions that could be explained by cloudiness. The maximum experimental values
      of the UVI were around 9 during the summer, though frequently passing this value
      at the inland measurement stations. The annual accumulated dose of irradiation on
      a horizontal plane has also been studied, as well as the evolution through the
      year in units of energy, standard erythemal doses and minimum erythemal doses,
      according to different phototypes.

PMID- 12194216
TI  - Adaptation of cyanobacteria to UV-B stress correlated with oxidative stress and
      oxidative damage.
AB  - Cyanobacteria must cope with the negative effects of ultraviolet B (280-315 nm)
      (UV-B) stress caused by their obligatory light requirement for photosynthesis.
      The adaptation of the cyanobacterium Anabaena sp. to moderate UV-B radiation has
      been observed after 2 weeks of irradiation, as indicated by decreased oxidative
      stress, decreased damage, recovered photosynthetic efficiency and increased
      survival. Oxidative stress in the form of UV-B-induced production of reactive
      oxygen species was measured in vivo with the oxidative stress-sensitive probe
      2',7'-dichlorodihydrofluorescein diacetate. Photooxidative damage by UV-B
      radiation, including lipid peroxidation and DNA strand breakage, was determined
      by a modified method using thiobarbituric acid reactive substances and
      fluorometric analysis of DNA unwinding. Photosynthetic quantum yield was
      determined by pulse amplitude-modulated fluorometry. The results suggest that
      moderate UV-B radiation results in an evident oxidative stress, enhanced lipid
      peroxidation, increased DNA strand breaks, elevated chlorophyll bleaching as well
      as decreased photosynthetic efficiency and survival during the initial exposure.
      However, DNA strand breaks, photosynthetic parameters and chlorophyll bleaching
      returned to their unirradiated levels after 4-7 days of irradiation. Oxidative
      stress and lipid peroxidation appeared to respond later because decreases were
      observed after 7 days of radiation. The survival curve against irradiation time
      exhibited a close relationship with the changes in photosynthetic quantum yield
      and DNA damage, with little mortality after 4 days. Growth inhibition by UV-B
      radiation was observed during the first 7 days of radiation, whereas normal
      growth resumed even under UV-B stress thereafter. An efficient defense system was
      assumed to come into play to repair photosynthetic and DNA damage and induce the
      de novo synthesis of UV-sensitive proteins and lipids, allowing the organisms to
      adapt to UV-B stress successfully and survive as well as grow. No induction of
      mycosporine-like amino acids (MAA) was observed during the adaptation of Anabaena
      sp. to UV-B stress in our work. The adaptation of the cyanobacterium correlated
      with and could be caused by the oxidative stress and oxidative damage.

PMID- 12194217
TI  - Improvement of tumor response by manipulation of tumor oxygenation during
      photodynamic therapy.
AB  - Photodynamic therapy (PDT) requires molecular oxygen during light irradiation to
      generate reactive oxygen species. Tumor hypoxia, either preexisting or induced by
      PDT, can severely hamper the effectiveness of PDT. Lowering the light irradiation
      dose rate or fractionating a light dose may improve cell kill of PDT-induced
      hypoxic cells but will have no effect on preexisting hypoxic cells. In this study
      hyperoxygenation technique was used during PDT to overcome hypoxia. C3H mice with
      transplanted mammary carcinoma tumors were injected with 12.5 mg/kg Photofrin and
      irradiated with 630 nm laser light 24 h later. Tumor oxygenation was manipulated
      by subjecting the animals to 3 atp (atmospheric pressure) hyperbaric oxygen or
      normobaric oxygen during PDT light irradiation. The results show a significant
      improvement in tumor response when PDT was delivered during hyperoxygenation.
      With hyperoxygenation up to 80% of treated tumors showed no regrowth after 60
      days. In comparison, when animals breathed room air, only 20% of treated tumors
      did not regrow. To explore the effect of hyperoxygenation on tumor oxygenation,
      tumor partial oxygen pressure was measured with microelectrodes positioned in
      preexisting hypoxic regions before and during the PDT. The results show that
      hyperoxygenation may oxygenate preexisting hypoxic cells and compensate for
      oxygen depletion induced by PDT light irradiation. In conclusion,
      hyperoxygenation may provide effective ways to improve PDT efficiency by
      oxygenating both preexisting and treatment-induced cell hypoxia.

PMID- 12194218
TI  - Mapping the light field of the Waldmann PDT 1200 lamp: potential for wide-field
      low light irradiance aminolevulinic acid photodynamic therapy.
AB  - A quantitative assessment of the light field produced by a Waldmann PDT 1200 lamp
      is presented. A photodiode detector array capable of measuring a beam diameter of
      30 cm was used to map the light field. The irradiance was measured as a function
      of voltage. For lamp-detector distances of 10 cm (central axis irradiance = 250
      mW/cm2), the spatial profile of irradiance was typically Gaussian. For lamp
      detector distances of 30 cm (central axis irradiance = 79 mW/cm2), the spatial
      profile appeared more hemispherical in shape but with some asymmetry. The
      relative percentage variation between the maximum and minimum irradiance with
      respect to the central axis irradiance was approximately 13% and 3%,
      respectively, for a beam width of 12 cm. Beyond a lamp-detector distance of 50 cm
      (central axis irradiance = 32 mW/cm2), the spatial profile of irradiance was
      observed to become more crater-like in structure, with a minimum on the central
      axis and an approximately symmetric peak at a radial distance of 9 cm from the
      center. The relative percentage variation of this peak irradiance with respect to
      the central axis irradiance was approximately 17%. At lamp-detector distances of
      70 and 90 cm (central axis irradiance = 19 and 13 mW/cm2, respectively), the
      beam's profile was asymmetric, and the irradiance was observed to increase from
      the center to a radial distance of 15 cm (beam width 30 cm). For a lamp-detector
      distance of 70 and 90 cm, the relative percentage variation between the maximum
      irradiance and the central axis irradiance was approximately 25% and 35%,
      respectively.

PMID- 12194219
TI  - Photodynamic properties of amphiphilic derivatives of aluminum
      tetrasulfophthalocyanine.
AB  - Photodynamic therapy (PDT) is a promising treatment modality that has recently
      been accepted in clinics as a curative or palliative therapy for cancer and other
      nonmalignant conditions. Phthalocyanines (Pc) are attractive photosensitizers for
      PDT because of their enhanced photophysical and photochemical properties. The
      overall charge and solubility of Pc play a major role in their potential
      usefulness for PDT. A series of amphiphilic derivatives of tetrasulfonated
      aluminum Pc (AlPcS4) was prepared by substituting one of the four sulfonate
      groups with aliphatic side chains of 4, 8, 12 and 16 carbon atoms. The
      photodynamic properties of the derivatives were compared with those of AlPcS4 and
      the adjacent disulfonated aluminum Pc. Parameters studied included reversed-phase
      high-performance liquid chromatography (HPLC) retention times, capacity to
      generate singlet oxygen (1O2), in vitro cell uptake and phototoxicity, as well as
      PDT response of transplantable EMT-6 tumors in mice. The monomerized AlPcS4
      derivatives showed similar or higher capacities to generate 1O2 as compared with
      the parent AlPcS4 as measured from relative L-tryptophan photooxidation yields.
      A549 cell uptake of the AlPcS4 derivatives decreased in the following order:
      AlPcS4(C16) > AlPcS4(C12) > AlPcS4(C8) > AlPcS4(C4). Human low-density
      lipoprotein at high concentrations (40 micrograms/mL) completely prevented
      uptake, whereas at 4 micrograms/mL uptake was decreased for the more lipophilic
      compounds and yet remained unaffected for the more hydrophilic dyes. Using the 3
      (4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, A549 cell
      survival was assessed; it showed that photocytotoxic activity varied directly
      with the HPLC retention times, i.e. more hydrophilic compounds were less
      phototoxic. As 1O2 yields were similar for the four substituted AlPcS4
      derivatives, it was postulated that the increased cytotoxic activity was caused
      by enhanced subcellular localization as a result of the long aliphatic side
      chains. These amphiphilic compounds proved to be photodynamically potent against
      the EMT-6 mouse mammary tumor model implanted in Balb/c mice. At dye doses of 0.2
      mumol/kg and a fluence of 400 J/cm2 complete tumor regression was observed with
      no morbidity. The substitution of AlPcS4 with long aliphatic chains on the
      macrocycle greatly enhances its photodynamic efficacy both in vitro and in vivo.

PMID- 12194220
TI  - Promotion of photodynamic therapy-induced apoptosis by the mitochondrial protein
      Smac/DIABLO: dependence on Bax.
AB  - Photodynamic therapy (PDT) using the second-generation photosensitizer
      phthalocyanine (Pc) 4 causes mitochondrial damage and induces apoptosis through
      the release of cytochrome c to the cytosol. Another protein of the mitochondrial
      intermembrane space, Smac/DIABLO (second mitochondria-derived activator of
      caspase/direct inhibitor of apoptosis-binding protein with low pI), is also
      released to the cytosol in response to apoptotic stimuli and promotes caspase
      activation by binding IAP. To investigate the possible role of Smac/DIABLO in
      apoptosis induced by Pc 4-PDT, we transfected Smac/DIABLO (tagged at its C
      terminus with green fluorescent protein [GFP]) into MCF-7c3 cells (human breast
      cancer MCF-7 cells stably transfected with procaspase-3) and DU-145 cells (human
      prostate cancer cells that express no Bax because of a frameshift insertion
      mutation). Confocal microscopy showed that recombinant Smac/DIABLO, like
      cytochrome c, localized to mitochondria and colocalized with MitoTracker Red.
      Three hours after exposure of MCF-7c3 cells to PDT (200 nM Pc 4 and 150 mJ/cm2
      red light), Smac/DIABLO-GFP, as well as cytochrome c, was found largely in the
      cytosol. In contrast, for DU-145 cells, both Smac/DIABLO-GFP and cytochrome c
      remained in the mitochondria after PDT. By staining with Hoechst 33,342, typical
      apoptotic nuclei were observed in MCF-7c3 cells, but not in DU-145 cells, after
      Pc 4-PDT. These results suggest that the release of Smac/DIABLO from mitochondria
      may be regulated by a Bax-mediated mechanism and that Smac/DIABLO may cooperate
      with the cytochrome c-dependent apoptosis pathway. In addition, in MCF-7c3 cells
      transfected by Smac/DIABLO-GFP, apoptosis induced by Pc 4-PDT was greater than in
      cells transfected with the GFP vector alone or in untransfected cells, as
      determined by flow cytometry. Thus, Smac/DIABLO promotes apoptosis after Pc 4-PDT
      in a Bax-dependent manner and may facilitate the passage of PDT-treated cells
      through the late steps of apoptosis.

PMID- 12194221
TI  - Selective action of the photosensitizer QLT0074 on activated human T lymphocytes.
AB  - A new photosensitizer, presently designated QLT0074, may have the potential for
      the treatment of immune and nonimmune conditions with photodynamic therapy (PDT).
      The activity of QLT0074 was tested against human peripheral blood T cells and
      Jurkat T lymphoma cells. At low nanomolar concentrations of QLT0074 in
      combination with blue light, apoptosis was rapidly induced in Jurkat and blood T
      cells in vitro as indicated by the expression of the apoptosis-associated
      mitochondrial 7A6 marker and Annexin-V labeling. Further studies performed with
      Jurkat T cells showed that PDT-induced apoptosis with QLT0074 was associated with
      caspase-3 activation and the cleavage of the caspase substrate poly(adenosine
      diphosphate-ribose)polymerase. Flow cytometry studies revealed that blood T cells
      with high expression of the interleukin-2 receptor (CD25) took up greater amounts
      of QLT0074 and were eliminated to a greater extent with PDT than T cells with low
      levels of this activation marker. This selective action of PDT was confirmed by
      similar reductions in the percentage of T cells that expressed other activation
      related markers, including very late activation antigen-4 (CD49d), human
      leukocyte antigen DR (HLA-DR), intercellular adhesion molecule-1 (CD54) and Fas
      (CD95). For activated T cells treated with a specific dose of QLT0074 and light
      24 h earlier, CD25 expression density was significantly less, whereas CD54, CD95
      and HLA-DR levels were similar to those for control cells treated with light
      alone. This work shows that PDT with QLT0074 exerts selective, dose-related
      effects on T cells in vitro.

PMID- 12194222
TI  - Assignment of UVB-responsive cis-element and protoplastization-(dilution-) and
      elicitor-responsive ones in the promoter region of a carrot phenylalanine ammonia
      lyase gene (gDcPAL1).
AB  - Expression of a carrot phenylalanine ammonia-lyase (PAL) gene (gDcPAL1) in
      suspension-cultured carrot cells is induced by dilution of the culture or by
      application of a fungal elicitor, as well as by ultraviolet B (UVB) irradiation.
      We demonstrated that among its upstream cis-elements (Takeda et al. [1997]
      Photochem. Photobiol. 66, 464-470), L4 is UVB responsive, and L1 is
      protoplastization- (dilution-) and elicitor responsive, from studies with
      transiently transformed mutated or truncated g-DcPAL1 promoter-luc constructs.
      This conclusion is consistent with our observation that PAL activities induced by
      UVB and by protoplastization (dilution) or elicitor are additive.

PMID- 12194223
TI  - [Vaccination against rabies in Poland].
AB  - The data on anti-rabies vaccination in Poland in the last fifteen years are
      presented. In general, 89,019 people were vaccinated against rabies in Poland in
      the years 1986-2000, among them 580 after deep bite by rabid animal and 4814
      after deep bite by an animal suspected of having rabies (III category of risk
      according to WHO). Among the patients with the III category exposition only a
      fraction were administered anti-rabies serum (12% of patients with deep bite by
      rabid animal), but this practice was becoming more frequent in recent years. 73%
      of patients were given vaccine after contact with domestic animals (dogs or
      cats), 9% after contact with wild foxes, which are the main reservoir of rabies
      in Poland. No cases of uneffective vaccination were observed. The preventive
      vaccination was sporadic and limited to persons with high professional risk of
      infection.

PMID- 12194224
TI  - [Active immunization against tick-born encephalitis (TBE) among border guards
      (1993-2002)].
AB  - Our experiences concerning of the vaccination program, started in 1993 and still
      continued, against tick-borne encephalitis in servicemen of Polish Border Guard
      are presented. In 1993-FSME IMMUN inject vaccine against TBE has been applied: 50
      Border Guard servicemen from Bialystok region were vaccinated. In 1994 another
      group of 1035 officers from 5 Border Guard Squadrons in endemic regions was
      vaccinated. From 1996 also was vaccinate Border Guard servicemen working with
      tracing dog. During the period 1993-2001 years 6846 persons were vaccinated. Only
      one case of mild Adverse Events Following Immunisation (AEFI) was noted
      (transient headache). Two TBE vaccines were used: "FSME IMMUN" Baxter and
      "Encepur" Chiron/Behring vaccines. There have been recognized any case of TBE
      among the vaccinating Border Guard Officers. Nevertheless (in a contemporary
      epidemiological situation of TBE in Poland) almost all the Border Guard
      servicemen are endangered with the o/m infection. In this condition active
      immunization program is in progress.

PMID- 12194225
TI  - [Evaluation of serum levels of tick-borne encephalitis (TBE) virus antibodies
      after administration of FSME inject vaccine].
AB  - OBJECTIVE: The purpose of this work was to evaluate the changes of anti-TBE virus
      antibodies serum concentration 3 months after administration of FSME Inject
      vaccine. METHODS: The detection of IgG antibodies against TBE virus was performed
      in sera of 106 forest workers aged mean = 41.5. These sera were examined twice
      before and after vaccine administration using FSME Kombi-Kit. According to
      producer's information the "safe" concentration, which protects from TBE virus
      infection, is over 11VE. RESULTS: In examination 126 (24.5%) sera showed
      concentration of examined antibodies lower than 11 VE but in 80 (75.5%) sera
      antibodies concentration was from 12 to 47 VE (mean = 24.15 VE). In the
      examination 2 significant increase of antibodies concentration was stated. In all
      sera the concentration ranged from 9 to 62 VE (mean = 39.83 VE). CONCLUSION: The
      administration of TBE vaccine booster causes quick increase of antibodies against
      TBE virus to the level which is considered to be protective against TBE virus
      infection.

PMID- 12194226
TI  - [Neurological complication of influenza infections].
AB  - The aim of this study was to present neurological complications of influenza
      infections. Infections caused by influenza viruses can be very serious and may
      lead even to death resulted from the post-infectious complications. The most
      often occurring complications are pneumonia, bronchitis, bronchiolitis,
      myocarditis and otitis media. The other group is neurological post-influenza
      complications, including dementia, epileptic disorders, cerebrovascular disease,
      febrile convulsions, toxic encephalopathy, encephalitis, meningitis, subarachnoid
      hemorrhages, lethargic encephalitis, psychosis or increase in the number of cases
      of Parkinson's disease. The first way of prevention of influenza is vaccination
      that results in healthy, social and economic benefits.

PMID- 12194227
TI  - [Neurologic problems in tick-borne diseases--clinical and diagnostic aspects].
AB  - Tick carried illnesses frequently lead towards neurological complications. The
      tick-borne encephalitis and borreliosis are the most frequently encountered
      illnesses having such aetiopathogenesis. In the study there are presented
      clinical aspects of tick-borne encephalitis and borreliosis with special
      consideration of various neurological symptomatology. Simultaneously there are
      discussed current diagnostic rules of the diseases, mainly on the basis of
      serologic investigation.

PMID- 12194228
TI  - [Mental disorders in the course of lyme borreliosis and tick borne encephalitis].
AB  - BACKGROUND: Lyme borreliosis is a chronic, multisystem disease, of prolong course
      with three consecutive stages, caused by a tick-transmitted spirochete Borrelia
      burgdorferi. Tick Borne Encephalitis (TBE) is neuroinfection caused by Tick Borne
      Encephalitis Virus (TBEV). OBJECTIVE: We evaluated the occurrence of psychiatric
      manifestations in the early phase of borreliosis-erythema migrans and
      neuroboreliosis as well as in its late phase--in arthritis and in the Tick-Born
      Encephalitis. The aim of the study was to single out the most frequent
      psychiatric symptoms and psychopathological syndroms and to determine their
      dynamics. METHODS: The study was carried out between 1999 and 2000 and comprised
      174 patients of the Department of Psychiatry and Department of Infectious and
      Neuroinfectious Diseases of Medical Academy in Bialystok. Seventy seven patients
      diagnosed with arthritis, 20 with neuroborreliosis, 26 with skin manifestation
      erythrema migrans and 51 with KZM participated. All subjects underwent
      psychiatric evaluation twice--during hospitalization and six month after
      discharge. Mental status examinations included general psychiatric examination
      and battery of scales and tests: Mini Mental State Examination, Beck Depression
      Inventory, Hamilton Depression Rating Scale, Hamilton Anxiety Rating Scale,
      Reitan's Trail Making Test, Choynowsky Memory Scale, Symptoms Inventory and
      neuropsychological testing. RESULTS: Both in the course of TBE and Lyme
      borreliosis the majority of patients experienced psychiatric problems in the
      acute phase of disease as well as in the late phase--3, 6 months after the onset
      of the disease. The most common psychiatric manifestations were depressive
      disorders--episodes of depression or organic mood disorders, and cognitive
      deficits which manifest themselves as mild cognitive disorder or dementia.
      CONCLUSION: Psychiatric assessment is important in early stage of kzm and
      borreliosis but first of all after termination of acute symptomatology.

PMID- 12194229
TI  - [Toxic and allergic action of tick saliva components].
AB  - The paper presents the role of bioactive components secreted by ticks in
      pathogenesis local and general reactions in the host. The salivary glands of
      ticks produce cement, enzymes and their inhibitors, histamine agonists and
      antagonists, antihemostatic factors, prostaglandins, and toxins. Tick feeding
      induces host inflammatory lesion and host immune responses.

PMID- 12194230
TI  - [New aspects of the pathogenesis of lyme disease].
AB  - Morphological changes of B. burgdorferi as well as changes in expression of
      surface proteins caused by environmental determinants are essential in
      pathogenesis of Lyme disease. Cysts, spherical form (spheroplasts, L-form) and
      "blebs" (gemmae) can be responsible for long lasting antigenic stimulation, signs
      of chronic borreliosis, and even probably connected with MS and Alzheimer
      disease. Mechanisms to avoid elimination and persistence in the host include:
      expression of low heterogenic Osp A, B replaced by polymorphic in sequence and
      antigenic reactivity OspC, the hindrance of access to some membrane proteins by
      other proteins on the spirochete's surface, effects of tick saliva proteins
      action. Hiding of spirochetes is possible by invagination into fibrocytes
      membrane as well as, coating by antigens derived from lymphocytes B. Distribution
      of spirochetes is facilitated by binding to platelets through integrin aIIb b3,
      and to the endothelial cells through integrins av b3 i a5b1, recognition of
      decorin by lipoproteins DbpA i DbpB, receptor for NAG (N-acetyl glucosamina).
      Endothelial cells, toxic products of granulocytes, monocytes, macrophages as well
      as phagocytosis counterpart in pathogenesis. Induced cytokines are connected with
      activation subsets of T lymphocytes involved in inflammatory response. Cytokines
      produced by Th1 as cytotoxic CD8 accompany the disease. Important are also
      dendritic cells regarded as initiators of Th1 response with participation of IL
      12. In pathogenesis of Lyme disease participation of autoimmunity is notified,
      especially molecular similarities between OspA and human lymphocytic antigen
      (hLFA-1). Neurotoxin, produced by B. burgdorferi Bbtox1 was identified.
      Encephalopathy signs in Lyme borreliosis could be result of releasing toxico
      metabolic products, ability of spirochetes to pass the blood-brain barrier as
      well as, effect of lymphocytes migration. Active invasion of brain endothelium as
      ability to adherence to endothelial wall could be the source of focused or
      disseminated inflammation of brain vessels. Antiaxonal antibodies could disturb
      axon conduction without damaging. But damage of white matter could be connected
      with damage of mielin production cells, probably by antibodies, induced in cross
      reaction.

PMID- 12194231
TI  - [Natural history of the HIV infection and changes in the central nervous system].
AB  - Central nervous system (CNS) becomes infected in early days of primary HIV
      infection. It is concerned to be one of the most important reservoirs of HIV in
      the human organism. It is also often affected by a number of conditions of
      different etiology, associated with HIV infection: opportunistic infections,
      neoplasms, disorders caused by HIV itself, adverse events of drugs, etc. These
      conditions appear in certain stages of HIV infection, connected with the state of
      the host's immunological system and degree of immunodeficiency. Unique
      physiological features of CNS cause that viral replication in CNS is to certain
      degree independent and different from systemic mechanisms of HIV infection. We
      overview the natural history of CNS HIV infection and common disorders of CNS
      associated with HIV regarding the stages of infection and possible mechanisms of
      viral entry to CNS and its progressive damage.

PMID- 12194232
TI  - [Immunopathogenesis of inflammatory arthritis: lesson from Lyme and rheumatoid
      arthritis].
AB  - Arthritis is a common manifestation of late Lyme disease and can develop into an
      erosive arthritis with histopathologic similarities to rheumatoid arthritis (RA).
      The development of persistent arthritis and in some cases cartilage and bone
      erosion is the result of autoimmune phenomena that develop after contact with
      Borrelia burgdorferi. Analysis of the host-pathogen interaction and
      immunopathogenic factors in Lyme arthritis are presented in this study.

PMID- 12194233
TI  - [PCR sensitivity in detection of DNA of Borrelia burgdorferi sensu lato in
      different isolates].
AB  - OBJECTIVE AND METHODS: Because of lack of standardization of PCR method in Poland
      to amplify Borrelia burgdorferi s. l. DNA in this case we applied three different
      primer sets for amplification of: fla gene, 16S rRNA small subunit gene as well
      as 5S-23S rRNA intergenic spacer and two different polymerases. We compare the
      efficacy of Borrelia burgdorferi s. l. detection in whole blood from borreliosis
      suspected patients and isolates of intestine contents of Ixodes ricinus ticks. A
      quality of polymerase is also important in sensitivity of PCR method. RESULTS:
      The best sensitivity of PCR was in blood with primers complementary to 16S rRNA
      gene, then in ticks isolates with primers complementary to fla gene. CONCLUSION:
      We affirm that results of PCR detection depend on genetic markers employed to DNA
      detection and DNA isolation method.

PMID- 12194234
TI  - [Concentration of sVAP in serum of patients with different forms of Lyme
      borreliosis].
AB  - OBJECTIVES: The aim of our work was to assess the serum concentration of soluble
      VAP-1 (sVAP-1) in patients with arthral type of borreliosis and erythema migrans.
      METHODS: We included in our study 30 patients in the age of 17-53 years who were
      treated for erythema migrans and 30 patients in the age of 25-63 years who were
      diagnosed with arthral type of borreliosis. The control group consisted of 30
      healthy blood donors. The diagnosis of borreliosis was made on the basis of
      anamnesis, physical examination and additional tests, one of which proved the
      existence of IgM and IgG antibodies against Borrelia burgdorferi antigen present
      in the serum of patients. All samples for investigations were taken in a single
      collection manner. The serum concentration of sVAP-1 protein was assessed with
      ELISA method. All data were analysed statistically. We assumed 5% risk of
      conclusion error. CONCLUSIONS: 1. We did not observe an increase in serum sVAP-1
      concentration in patients with erythema migrans compared to the control group.
      All observed differences in the serum level of this protein seemed to be random
      ones. 2. We showed a statistically important increase in soluble sVAP-1 serum
      concentration in patients with arthral type of borreliosis compared to the
      control group.

PMID- 12194235
TI  - [Ophthalmic manifestations in Lyme borreliosis].
AB  - We reviewed ophthalmic manifestations in Lyme borreliosis, concentrating on
      clinical and laboratory diagnosis, differential diagnosis and treatment options.
      Ocular involvement may occur in every stage of the disease. Conjunctivitis and
      episcleritis are the most frequent manifestations of the early stage. Neuro
      ophthalmic disorders and uveitis occur in the second stage whereas keratitis,
      chronic intraocular inflammation and orbital myositis have been reported in the
      third stage of borreliosis.

PMID- 12194236
TI  - [The role of anti-influenza vaccination in elderly persons].
AB  - Aging is associated with an increased risk of viral infections such as influenza.
      Moreover, elderly individuals are susceptible to serious post-influenza
      complications: viral and bacterial pneumonia, myocarditis and myocardial injury,
      rhabdomyolysis as well as pulmonary thromboembolism. Mortality due to influenza
      is very high in the elderly and especially in those with chronic respiratory and
      circulatory diseases. The efficacy of influenza vaccination in the elderly is
      high in prevention of influenza and in reduction of hospitalizations for
      pneumonia, other respiratory conditions and in lowering death rates for all
      causes. Especially profitable are annually repeated vaccinations. Lack of an
      adequacy between titer of the protective anti-haemagglutinin antibodies and
      clinical protection may be due to the age-related changes in immune response. An
      assessment of cytolytic T cells activity together with cytokines, measured in
      tests in vitro, age good measures of vaccine effectiveness. Besides its specific
      protectory effect, influenza vaccination may also non-specifically stimulate NK
      cells and type I immune response. Thus, regular annually repeated influenza
      vaccinations are not only protective but also may modulate immune response.

PMID- 12194237
TI  - [WSIS "Biomed" S. A. in Cracow--vaccinations against some widespread infectious
      diseases].
AB  - The history, present practice and perspectives of vaccination against some
      widespread infectious diseases are discussed, with special focus on the role of
      booster vaccination. It is noted that the level of protective antibodies against
      diphtheria and pertussis falls within years after vaccination. In case of
      diphtheria, with the current vaccination scheme existing in Poland, population
      over 30 years old shows significant susceptibility to the infection, which could
      be effectively reduced by booster vaccination of adults in 10 years intervals.
      Vaccination of infants against pertussis was accompanied by growing morbidity in
      elder children and adults. At present, introducing another dose of pertussis
      vaccine, preferably acellular, at 5 years age is suggested. Hepatitis B remains
      significant problem in Poland and world-wide, but current vaccination policy
      gives opportunity to reduce its incidence. Existing vaccines appear highly
      effective, and the immunity is long lasting.

PMID- 12194238
TI  - [Spontaneous activity of neural membranes].
AB  - Many neurons of the vertebrate and invertebrate central nervous system (CNS)
      exhibit rhythmic oscillations of membrane potentials in absence of external
      stimuli. Spontaneous firing of these cells generates the activity in various
      areas of CNS. Firing patterns produced by autoactive neurons and role of several
      ionic conductances in driving membrane potential to the threshold of action
      potential generation is described.

PMID- 12194239
TI  - [Molecular basis of ion selectivity based on crystalline structure of bacterial
      channels].
AB  - The principles of ionic selectivity of the two crystallised bacterial ion
      channels are described. These channels are: the potassium channel KcsA, whose
      amino-acid sequence is homologous to the eukaryotic voltage--dependent potassium
      channels and the chloride channel EcClC that is a prokaryotic member of the ClC
      family of chloride channels. IN CONCLUSION: although the overall molecular
      architecture of KcsA is different from that of EcClC, the selectivity filters in
      both cases show similarities. They both utilise helix dipoles organised within
      the channel molecule in such a fashion to produce electrostatically favourable
      environment for anions (in the case of EcClC) or cations (in the case of KcsA).

PMID- 12194240
TI  - [Functional analysis of evoked potentials in rat sensory cortex].
AB  - In the barrel cortex of behaving rat potentials evoked to vibrissa stimulation
      are composed from two main principal components which can be attributed to
      activation of two pyramidal cell populations: supra- and infragranular. The
      classical aversive stimulus favors the appearance of EPs dominated by a component
      characteristic of infragranular cells. We hypothesize that neuromodulatory action
      elicited by contextual stimulation activates all involved cortical neurons which
      results in opening the transmission gate to the surrounding columns.

PMID- 12194241
TI  - [Interaction between cerebellar neurons].
AB  - Cross-correlation methods were applied to examine interaction between the
      cerebellar cortex and the interaction between Purkinje neurons and neurons of the
      deep cerebellar nuclei. Patterns of interaction between different cerebellar
      cortical neurons are described.

PMID- 12194242
TI  - [Effect of changes in extracellular pH on GABAA receptors in neurons].
AB  - Local pH values of both intra- and extracellular liquids can be regulated by a
      number of mechanisms including membrane transport and metabolism. It is known
      that the changes of extracellular pH accompanying physiological and pathological
      processes are sufficient to affect several important structures such as ionic
      channels, transporters, receptors etc. In particular, several reports indicate
      that GABAA receptor is strongly modulated by this factor. The effect of pH on
      these receptors strongly depend on the subtype of GABAA receptor (subunit
      composition). The application of ultrafast perfusion system allowed to explore
      the mechanisms of pH effect on GABAA receptors in neurons. It is concluded that
      changes in pH exert their effects by allosteric modulation of GABAA receptors.

PMID- 12194243
TI  - [Role and function of voltage-gated chloride channels of the CIC family and their
      defects leading to genetic diseases].
AB  - There are 9 channels of the ClC family in mammals and few others in fishes,
      plants, yeast and bacteria. The ClC channels are present in different tissues and
      play a role in transmembrane potential stabilization, transepithelial transport,
      cell volume regulation, acidification of intracellular organelles. The genetic
      defects of ClC-1 chloride channel lead to myotonias, the defect in ClC-5 channel
      to the formation of stones in kidney, while the defect in ClC-Kb channel leads to
      the Bartter's syndrome.

PMID- 12194245
TI  - [Eruption of neuronal activity in selected structures of the mammalian brain].
AB  - Slow bursting activity of the cells in the hypothalamus of the mammalian brain is
      described, with a special emphasis on the vasopressinergic neurons of the
      supraoptic and paraventricular nuclei (SON/PVN). This patterned activity is
      compared to the one observed in the thalamic structure--the intergeniculate
      leaflet of the lateral geniculat nucleus (IGL). Histograms of activity, bimodal
      distributions of the frequencies, averaged bursts and a few other characteristic
      properties of the oscillatory activity observed in SON/PVN and IGL are shown.
      Slow bursting activity of the intergeniculate leaflet cells is suggested to have
      a same function as has patterned firing of hypothalamic cells. Peptidergic
      contents of IGL cells, possibly attenuated blood-brain barrier in the area of
      this structure and its role in the adjustment of the circadian rhythms are some
      of the arguments to support this hypothesis.

PMID- 12194244
TI  - [Mitochondrial ion channels].
AB  - Ion channels selective for potassium or chloride ions are present in inner
      mitochondrial membranes. They are probably important in cellular events such as
      regulation of organelle volume changes. Additionally, mitochondrial potassium
      channels are targets for potassium channel openers and antidiabetic
      sulfonylureas. This review describes properties, and current hypotheses
      concerning the functional role of mitochondrial ion channels.

PMID- 12194246
TI  - [Electrophysiologic examination of the circadian clock in mammals].
AB  - The mammalian circadian time-keeping system is established by two major neural
      structure: the suprachiasmatic nucleus (SCN) of the anterior hypothalamus and the
      intergeniculate leaflet (IGL) of the thalamus. Both these structures display the
      ultradian isoperiodic oscillation of the level of neuronal firing which probably
      constitute a basic activity necessary to generate circadian rhythms. In the
      present study we discuss the nature, pharmacology and the serotonergic influences
      on this oscillation in IGL.

PMID- 12194247
TI  - [Petit-mal epilepsy in laboratory rats, issues that an experimenter should be
      remember].
AB  - A certain proportion of laboratory rats of various strains is characterized with
      a heritable, abnormally high propensity for spontaneous, nonconvulsive
      electrocortical seizures. The seizures have form of bursts of spike-wave
      discharges (SWD) reminiscent of the human petit-mal epilepsy. The experimenter is
      usually unaware of this fact. The paper concerns the question of reliability of
      results obtained on rats samples derived from populations nonhomogenous with
      respect to the high propensity for SWD seizures.

PMID- 12194248
TI  - [Laminar profiles of theta rhythm amplitude and phase in sections of hippocampal
      formation in vitro].
AB  - Amplitude and phase profiles of theta rhythm induced in the hippocampal formation
      slices by bath perfusion of carbachol was studied. Amplitude and phase profiles
      obtained in vitro closely resemble profiles of spontaneous theta rhythm recorded
      in freely behaving or anaesthetised rats. Electrotonic mechanism underlying the
      in vivo and in vitro theta are discussed.

PMID- 12194249
TI  - [Nociceptive neurons].
AB  - Pain is generated by activation of specific dorsal root ganglion (DRG) neurons
      termed the nociceptive neurons. The nociceptive DRG neurons express 3 categories
      of ionic channels a. channels gated by pain stimuli, b. channels responsible for
      the transmission of information from sensory receptors to the spinal cord, c.
      channels responsible for the release of neurotransmitters in the spinal cord.
      There is evidence that kinetic properties, molecular structure and functional
      significance of the ionic channels expressed in nociceptive DRG neurons are
      different compared to the other types of DRG neurons. The ionic channels are
      strictly controlled by receptors for neurotransmitters expressed in the plasma
      membrane of nociceptive DRG neurons.

PMID- 12194251
TI  - [Synaptic plasticity in the motor cortex].
AB  - Horizontally-oriented intracortical connections have been proposed to serve as a
      substrate for plastic reorganizations of adult motor cortex. N-methyl-D-aspartate
      (NMDA) receptor-dependent long-term potentiation (LTP) of synaptic efficacy is a
      candidate mechanism of these reorganizations in mammalian species ranging from
      rats to humans. The acquisition of a motor skill is accompanied by increased
      strength of synaptic connections within adult rat primary motor cortex, most
      likely due to LTP-like mechanisms.

PMID- 12194250
TI  - [Use of models for spontaneous paroxysmal activity in studies of adaptive changes
      in serotonin receptors].
AB  - Certain antidepressant medications exert effects on the serotonergic (5-HT)
      system but their mechanisms are still not well understood. Using extracellular ex
      vivo recording of spontaneous, epileptiform activity of neurons we determined
      changes in the reactivity of cortical and hippocampal slices to agonists of main
      subtypes 5-HT receptors, induced by repeated administration of the
      antidepressants. Repeated treatment with antidepressants enhances the 5-HT
      mediated inhibition in both frontal cortex and hippocampal regions. Drugs
      administration induce opposite adaptive changes within 5-HT2 and 5-HT1A receptors
      in frontal cortex as well as in 5-HT1A and 5-HT4 receptors in the hippocampus.
      These effects may contribute to therapeutic effects of antidepressants
      administration.

PMID- 12194252
TI  - [Patch-clamp technique in investigations of potassium channel activation in T
      lymphocytes].
AB  - This review focuses on results of patch-clamp studies on modulation of T
      lymphocyte potassium channel activity by physiologically relevant factors. In the
      preface the patch-clamp technique is briefly presented and basic properties of
      potassium channels in T lymphocytes are characterised. The paper contains an
      overview of the data on modulatory effects of extracellular and intracellular pH,
      temperature, extracellular potassium, extracellular divalent and trivalent metal
      cations, channel phosphorylation processes and membrane lipid metabolities on
      potassium channel activity. Some still unresolved problems in that area are
      indicated.

PMID- 12194254
TI  - The pharmacologic versatility of a neurotoxic polypeptide.

PMID- 12194253
TI  - [Density of theta as a new parameter characterizing field activity in hippocampal
      formation of cats].
AB  - Our experiments conducted in the last decade on freely moving cats, showed that
      commonly used theta parameters: frequency, amplitude and power are not sufficient
      for a precise characterization of theta field activity. It is specially seen in
      condition when the experimental protocol involves sensory or chemical stimulation
      in order to induce hippocampal theta. We described a novel theta parameter-
      "theta density", that allows more adequate quantitative evaluation of this EEG
      pattern in freely moving cats.

PMID- 12194255
TI  - [Electroencephalographic (EEG) activity recorded in brain tissue in vitro].
AB  - The generation of theta in the limbic cortex is a prime example of rhythmical
      activity involving central mechanisms of oscillations and synchrony. It was
      demonstrated that bath perfusion of hippocampal slices with carbachol resulted in
      theta-like oscillations. A number of our experiments have provided a strong
      evidence that theta-like activity recorded in vitro replicates pharmacological
      and physiological properties of in vivo recorded theta.

PMID- 12194257
TI  - Buruli ulcer disease. Mycobacterium ulcerans infection.

PMID- 12194258
TI  - Web-based tool for early warning of malaria epidemics in Africa: monitoring
      current rainfall anomalies in zones at epidemic risk.

PMID- 12194259
TI  - Molecular dynamics simulation of a DNA containing a single strand break.
AB  - Molecular dynamics simulations were performed for a dodecamer DNA containing a
      single strand break (SSB), which has been represented by a 3'-OH deoxyribose and
      5'-OH phosphate in the middle of the strand. Molecular force field parameters of
      the 5'-OH phosphate region were determined from an ab initio calculation at the
      HF/6-31G level using the program package GAMESS. The DNA was placed in a periodic
      boundary box with water molecules and Na+ counter-ions to produce a neutralised
      system. After minimisation, the system was heated to 300 K, equilibrated and a
      production run at constant NTP was executed for 1 ns using AMBER 4.1. Snapshots
      of the SSB-containing DNA and a detailed analysis of the equilibrated average
      structure revealed surprisingly small conformational changes compared to normal
      DNA. However, dynamic properties calculated using the essential dynamics method
      showed some features that may be important for the recognition of this damage by
      repair enzymes.

PMID- 12194260
TI  - Simulation of 125I induced DNA strand breaks in a CAP-DNA complex.
AB  - The E. coli catabolite gene activator protein (CAP)-DNA complex with 125I located
      at the position of the H5 atom of the cytosine near the centre was incorporated
      into the PARTRAC track structure code. DNA strand breaks due to irradiation were
      calculated by track structure and radical attack simulations; strand breaks due
      to neutralisation of the highly charged 125Te ion were derived from a semi
      empirical distribution. According to the calculations, the neutralisation effect
      dominates the strand breakage frequency at 2 bases away from the 125I decay site
      on both strands. The first breakage distribution counted from a 32P labelled end
      on the strand with 125I agreed well with experimental data, but on the opposite
      strand, the calculated distribution is more concentrated around the decay site
      and its yield is about 20% larger than the measured data.

PMID- 12194261
TI  - Monte Carlo simulations of DNA damage from incorporated cold iodine following
      photoelectrically induced Auger electron cascades.
AB  - Radiation-induced damage in nucleosomal DNA from Auger electron cascades due to
      incorporated cold IUdR has been modelled through Monte Carlo simulations.
      Probabilities of DNA double strand break (DSB) production following a vacancy in
      the K, L, M and N shells of iodine are estimated. DSB complexity from the base
      damage accompanying a break was also estimated. Multiple DSB events were analysed
      for correlated breaks due to nucleosome periodicity. The probability of an Auger
      cascade causing at least one DSB strongly depended on the shell in which the
      initial vacancy was produced. This probability was approximately 0.35 for K and L
      shells and fell to 0.02 for the N shell. As expected, DSBs were predominantly
      induced in a nucleosome containing incorporated iodine and were accompanied with
      extensive base damage. Analysis of multiple DSB events showed that approximately
      14% of the DSBs produced following a vacancy in the L1 orbital can be interpreted
      as correlated with base pair separation attributable to the nucleosome
      periodicity. The data generated in this work provide a basis for the development
      of photon-activation therapy using kilovoltage X rays incident upon IUdR
      sensitised tumours.

PMID- 12194262
TI  - The fidelity of repair of radiation damage.
AB  - Ionising radiation (IR) induces a range of DNA damage similar to that which
      arises endogenously from reactive oxygen species generated as by-products of
      metabolism. However, due to non-homogeneous energy deposition, the damage from IR
      frequently occurs in clusters producing unique 'complex' lesions. Cells have
      evolved a range of mechanisms to respond to DNA damage, which include pathways of
      DNA repair and processes that prevent the proliferation of damaged cells.
      However, the repair mechanisms are not fool proof and clustered radiation-induced
      lesions pose a particular problem. Whether DNA damage created by IR can be
      repaired accurately, mis-repaired or not repaired at all is of utmost importance
      in considering the impact of radiation exposure. Here, the current knowledge is
      discussed of the repair of double strand breaks, a biologically important lesion
      induced by IR, in the context of the fidelity of the repair mechanisms and the
      consequences of mis-repair or lack of repair.

PMID- 12194263
TI  - Induction and repair of DNA damage in human cells at different stages of
      differentiation.
AB  - Use of cellular systems capable of undergoing in vitro differentiation can give
      useful information on the basic mechanisms of cellular radiation sensitivity.
      During differentiation the cellular organisation, including the nuclear structure
      and the intracellular concentration of several compounds and enzymes change
      drastically. Accordingly, radiation response to ionising radiation is also
      expected to change. The human proerythroblastoid cell line K562 can be induced to
      pseudoerythroid differentiation. This process has been characterised and studies
      have been carried out on DNA single strand break and double strand break
      induction and repair before and after differentiation commitment. Rejoining
      studies have been performed for both types of damage and correct double strand
      break rejoining has been also measured in particular genomic locations. An
      overview is presented of these results together with preliminary data recently
      obtained on radiation induced DNA fragmentation as a function of radiation
      quality.

PMID- 12194264
TI  - Physical and biological parameters affecting DNA double strand break misrejoining
      in mammalian cells.
AB  - In an attempt to investigate the effect of radiation quality, dose and specific
      repair pathways on correct and erroneous rejoining of DNA double strand breaks
      (DSBs), an assay was applied that allows the identification and quantification of
      incorrectly rejoined DSB ends produced by ionising radiation. While substantial
      misrejoining occurs in mammalian cells after high acute irradiation doses,
      decreasing misrejoining frequencies were observed in dose fractionation
      experiments with X rays. In line with this finding, continuous irradiation with
      gamma rays at low dose rate leads to no detectable misrejoining. This indicates
      that the probability for a DSB to be misrejoined decreases drastically when DSBs
      are separated in time and space. The same dose fractionation approach was applied
      to determine DSB misrejoining after alpha particle exposure. In contrast to the
      results with X rays, there was no significant decrease in DSB misrejoining with
      increasing fractionation. This suggests that DSB misrejoining after alpha
      irradiation is not significantly affected by a separation of particle tracks. To
      identify the enzymatic pathways that are involved in DSB misrejoining, cell lines
      deficient in non-homologous end-joining (NHEJ) were examined. After high X ray
      doses, DSB misrejoining is considerably reduced in NHEJ mutants. Low dose rate
      experiments show elevated DSB misrejoining in NHEJ mutants compared with wild
      type cells. The authors propose that NHEJ serves as an efficient pathway for
      rejoining correct break ends in situations of separated breaks but generates
      genomic rearrangements if DSBs are close in time and space.

PMID- 12194265
TI  - Double strand break rejoining after irradiation of human fibroblasts with X rays
      or alpha particles: PFGE studies and numerical models.
AB  - When a charged-particle track intercepts the chromatin fibre in DNA of mammalian
      cells, clustered damage is induced depending on the DNA conformation, local
      environment and track structure. Intra-track correlated DNA damage may have a
      higher probability of being mis-repaired or left un-repaired. Fragment size
      distributions of DNA double strand breaks (DSBs) induced in primary human
      fibroblasts by 240 kVp X rays and 238Pu alpha particles (110 keV.micron-1) were
      resolved using pulsed-field gel electrophoresis (PFGE). By monitoring DSB
      rejoining kinetics and changes in the fragment size distribution with repair
      time, the relevance of spatial association of DSBs in determining rejoining
      kinetics was investigated. Rejoining kinetics appeared bi-phasic and independent
      of the size of the DNA fragments for both radiation qualities, with high LET
      radiation-induced DSBs repairing more slowly. Results suggest that local
      complexity of individual DSBs, rather than spatial association with other breaks
      is more significant in the determination of rejoining kinetics.

PMID- 12194266
TI  - Radiation quality dependence of DNA damage induction.
AB  - Analysis of DNA fragmentation and repair in relation to radiation quality may
      give important information about the role of break complexity and correlated
      double strand breaks (DSBs). DNA fragment analysis was performed by pulsed-field
      gel electrophoresis after exposure to different radiation qualities. Normal human
      fibroblasts were irradiated with boron ions (40, 80 and 160 keV.micron-1),
      nitrogen ions (80, 125, 175 and 225 keV.micron-1) and neon ions (225 and 300
      keV.micron-1). The amount of DNA less than 1.1 Mbp decreased with increasing
      linear energy transfer (LET) for all three ions. When theoretical random
      distributions were subtracted from the experimental data for 225 keV.micron-1
      nitrogen ions in all size intervals (5-5700 kbp), there was a significant non
      random distribution of DSBs for sizes up to 1-3 Mbp. This non-random distribution
      of breaks, probably produced by intra-track correlated DSBs, may constitute a
      substantial portion of the high-LET induced DSBs.

PMID- 12194267
TI  - Investigation of radiation damage in DNA by using atomic force microscopy.
AB  - The effect of radiations on supercoiled plasmid DNA has been investigated by
      using atomic force microscopy (AFM). The DNA molecules were deposited on a
      substrate and observed by AFM. Alternatively, DNA at different scavenger
      concentrations was initially exposed to different types of radiations (alpha and
      X rays) at various doses. After irradiation, fragments (open circular and
      linearised strands) were observed corresponding to single strand breaks and
      double strand breaks in DNA. This result indicates the capabilities of AFM for
      the qualitative detection of strand modifications due to irradiation. The amount
      of each class of topology enables a quantitative response to be determined for
      both types of radiation (alpha, X). A value of the radiosensitivity of DNA was
      obtained as a function of the scavenger concentration. Strong accordance was
      found between AFM results and those obtained by use of gel electrophoresis. The
      advantage of AFM in comparison with traditional techniques is the possibility of
      analysing the radiation effects on one molecule. Indeed, taking the example of
      alpha particles, it is shown that it is easy to measure the sizes of linear
      strands by AFM. Such additional or even precise results are difficult to obtain
      with gel electrophoresis since, in such a case, data are lost through smearing.

PMID- 12194268
TI  - The production of single strand and double strand breaks in DNA in aqueous
      solution by vacuum UV photons below 10 eV.
AB  - The mechanisms of break formation in fully hydrated DNA have been investigated
      using monochromatic photons below 10 eV. This has been achieved by developing a
      novel 'wet cell' for irradiating DNA in aqueous solution. Our preliminary data
      show that 7-10 eV photons readily induce strand breaks even though almost all of
      the energy is absorbed in the water. Therefore, the mechanism for the induction
      of single and double strand breaks (SSBs and DSBs) most likely involves indirect
      damage by OH radicals and is substantiated by data from studies in the presence
      of the OH radical scavenger Tris, which showed a substantial protective effect.
      The dose-effect curve for DSB induction is seen to be linear, or near-linear,
      indicating the involvement of 1-hit mediated induction of DSBs. These data point
      to single-event induction of DSBs being a significant pathway with all radiation
      types.

PMID- 12194269
TI  - Thirteenth symposium on microdosimetry.

PMID- 12194270
TI  - Biophysical analysis of radiation induced initial DNA fragmentation.
AB  - Production of double strand breaks (DSBs) and double-stranded DNA fragments after
      irradiation with high energy nitrogen ions was simulated with stochastic track
      generation and a high-order chromatin structure (HOCS) model representing a
      segment of interphase chromosome. The non-random distribution of DNA fragments is
      predicted for irradiation of HOCS. Agreement with the experimental data is
      obtained. The influence of HOCS and the role of the background component in DNA
      fragment distributions are discussed.

PMID- 12194271
TI  - Chromatin damage induced by fast neutrons or UV laser radiation.
AB  - Chromatin samples from livers of Wistar rats were subjected to fast neutron
      irradiation in doses of 10-100 Gy or to a 248 nm excimer laser radiation, in
      doses of 0.5-3 MJ.m-2. The action of the radiation on chromatin was monitored by
      chromatin intrinsic fluorescence and fluorescence lifetimes (of bound ethidium
      bromide to chromatin) and by analysing fluorescence resonance energy transfer
      between dansyl chloride and acridine orange coupled to chromatin. For the
      mentioned doses of UV excimer laser radiation, the action on chromatin was more
      intense than in the case of fast neutrons. The same types of damage are produced
      by the two radiations: acidic and basic destruction of chromatin protein
      structure, DNA strand breaking and the increase of the distance between DNA and
      proteins in chromatin.

PMID- 12194272
TI  - Induction of DNA double strand breaks in scid cells by carbon ions.
AB  - The DNA double strand breaks (DSBs) induced by X ray and carbon ion beam
      irradiation in scid cells were analysed using pulsed-field gel electrophoresis.
      Scid cells and hybrid cells were ideal to study the DNA DSB repair mechanisms,
      because their genetic backgrounds were identical except DNA-PK activity.
      Induction of DNA DSBs was determined after exposure to X rays and carbon beams.
      DNA DSB repair was by biphasic kinetics with a fast and a slow component. For
      scid cells only a slow component was observed, whereas the kinetics of DSBs
      repair was biphasic with a fast and a slow component. It was concluded from the
      experimental data that the induced DSB rejoining in scid cells was due to the
      lack of DNA-PK activity.

PMID- 12194273
TI  - Bystander effects: intercellular transmission of radiation damage signals.
AB  - Biological effects were examined in confluent cultures of fibroblasts and
      epithelial cells exposed to very low mean doses of alpha radiation, doses by
      which only 1-2% of the cells were actually traversed by an alpha particle.
      Enhanced frequencies of sister chromatid exchanges and HPRT mutations occurred in
      the non-irradiated, 'bystander' cells associated with a similar increase in the
      frequency of micronuclei, indicating the induction of DNA damage in these cells.
      In order to gain information concerning molecular pathways, changes in gene
      expression were examined in bystander cells by western analysis and in situ
      immunofluorescence staining. The expression levels of p53, p21 and MDM2 were
      significantly modulated in bystander cells; the damage signals leading to these
      changes were transmitted from irradiated to bystander cells by gap junction
      mediated intercellular communication. The bystander response was suppressed by
      incubation with superoxide dismutase as well as an inhibitor of NADPH oxidase,
      suggesting the effect may be mediated by oxidative stress. To examine other
      signalling pathways responsive to oxidative stress, the activation of stress
      related kinases and their downstream transcription factors were analysed in
      bystander cells by western blotting and electrophoretic mobility shift assays; a
      2-4-fold increase in the phosphorylation levels of JNK, ERK1/2, p90RSK, Elk-1 and
      ATF2 was observed. These changes were detected by 15 min after irradiation and
      persisted for at least 1 h. These findings indicate the activation of multiple
      signal transduction pathways in bystander cells, involving signals arising from
      the plasma membrane as well as from DNA damage.

PMID- 12194274
TI  - Characterisation of a bystander effect induced in human tissue explant cultures
      by low let radiation.
AB  - The existence of a bystander effect following both alpha and gamma irradiation of
      many cell lines is not now in dispute. The significance of this effect for cancer
      risk assessment and radiotherapy treatment planning requires demonstration of its
      relevance in vivo. The problem in demonstrating the existence of the effect in
      vivo is that other systemic effects may mask or confound the effect being
      investigated and it is practically impossible to attribute an effect in a
      particular cell to a signal produced in another irradiated cell. To approach this
      problem, an assay has been developed where fragments of human tissue can be
      irradiated ex vivo and the media harvested and added to unirradiated, clonogenic
      cells which have a well characterised and stable response to the bystander
      signal. The variation in the production of a signal from patient to patient can
      thus be assessed. The results of a study using tissue from over 100 patients
      attending Beaumont and St Vincent's Hospitals in Dublin for investigation of
      urological disorders including follow-up after treatment for transitional cell
      carcinoma (TCC) and resection of suspect prostatic lesions, are now available.
      Blood samples from the prostate group were also obtained. The results show that
      there is variation in the effect of the signal produced by irradiated tissue from
      different patients. This holds for bladder, prostate and blood. Gender, smoking
      status and the existence of a malignancy influence the expression of the signal
      by normal tissue. Male gender, smoking and a pre-existing malignancy all reduce
      the amount or effect of the signal produced into medium when the tissue is
      exposed. The effects of exposure to medium containing the signal are transmitted
      to distant progeny of the exposed cell population. The results may be important
      not only for understanding radiation risk mechanisms for protection but also for
      radiotherapy treatment planning where they may open new avenues for development
      of drugs for combined therapy.

PMID- 12194275
TI  - Early events in the apoptotic cascade initiated in cells treated with medium from
      the progeny of irradiated cells.
AB  - Genomic instability and the bystander effect have recently been linked
      experimentally. It has previously been shown that medium from irradiated cells
      can induce early events in the apoptotic cascade, such as mobilisation of
      intracellular calcium, loss of mitochondrial membrane potential and an increase
      in reactive oxygen species, in unhit cells. The aim of this study was to
      determine if medium from the progeny of irradiated cells could also initiate
      apoptosis in unhit cells. Human keratinocytes were irradiated (0.5 and 5 Gy) and
      medium was harvested up to the 7th passage post-irradiation and transferred to
      unirradiated keratinocytes. Intracellular calcium levels, mitochondrial membrane
      potential and the level of reactive oxygen species were all monitored for a
      period of 24 h following medium transfer. Rapid calcium fluxes (within 30 s),
      loss of mitochondrial membrane potential and increases in reactive oxygen species
      (from 6 h after medium transfer) were observed. There was no significant
      difference between medium generated by cells irradiated at the different doses.
      The data suggest that initiating events in the apoptotic cascade were induced in
      unhit cells by a signal produced by irradiated cells and that this signal can
      still be produced in the progeny of irradiated cells.

PMID- 12194276
TI  - Microdosimetry: reflections on Harald Rossi.
AB  - This and twelve previous Symposia reflect the evolution of microdosimetry, a
      field of research that has determined major new developments in radiation
      research, radiation protection, and radiology during the past four decades. The
      concepts of microdosimetry and its techniques were developed almost single
      handedly by H. H. Rossi. This memorial lecture outlines some of the ideas and
      some of the work of Harald Rossi that led to microdosimetry. It describes its
      major impact on radiobiology and, especially, its impact on studies with fast
      neutrons and on risk assessment. Microdosimetry was primarily designed as a tool
      for the elucidation of basic mechanisms of radiation action, but it has found its
      most important applications in the dosimetric measurement techniques that have
      become indispensable in radiation protection and in the dosimetry for radiation
      therapy. The advances of molecular biology are now providing new possibilities
      for a quantitative application of microdosimetry to radiobiology along the lines
      that Harald Rossi defined.

PMID- 12194277
TI  - The effect of low doses of gamma irradiation on the homeostasis of intracellular
      calcium in lymphocyte cells of rats.
AB  - The influence of acute and chronic gamma irradiation (0.25 and 0.5 Gy doses) on
      rat lymphocytes was examined on the 1st and 10th days after irradiation. Acute
      gamma irradiation increased the intracellular calcium concentration in the
      cytoplasm of the lymphocytes on the 1st day after the influence of the radiation.
      Calcium concentration returned to the control level on the 10th day after the
      effect of the radiation at all the doses. In the lymphocytes after acute
      irradiation the increase of the Ca2+ concentration in the intracellular depots on
      the 1st day was observed. Changes were also observed in the physicochemical state
      of the plasma membrane of these cells. Research on the influence of prolonged
      gamma irradiation on intracellular calcium homeostasis revealed opposite effects
      in comparison with acute gamma irradiation.

PMID- 12194278
TI  - Nuclear architecture and radiation induced chromosome aberrations: models and
      simulations.
AB  - Knowledge of radiation track structure and its interaction with biological
      targets is a fundamental starting point in understanding the mechanisms
      underlying the induction of biological damage. In this context Monte Carlo codes
      are a powerful tool of investigation, allowing one to simulate both track
      structure and the features of the target(s) of interest at different scales, from
      nanometres (linear dimensions of DNA) to micrometres (linear dimensions of human
      cell nuclei and interphase chromosome territories). In the light of recent
      experimental findings on nuclear architecture, different approaches in modelling
      chromosome structure and aberration induction are discussed. In particular, a
      model is presented in which chromosome territories were explicitly described as
      subnuclear regions and aberration induction was modelled by coupling the
      structure of the target with that of the radiation track. Comparisons between
      model predictions and experimental results from the literature are also reported.

PMID- 12194279
TI  - Vibrational energy relaxation: proposed pathway of fast local chromatin
      denaturation.
AB  - The molecular mechanism responsible for the alpha component of exchange-type
      chromosome aberrations, of chromosome fragmentation and of reproductive cell
      death is one of the unsolved issues of radiation biology. Under review is whether
      vibrational energy relaxation in the constitutive biopolymers of chromatin,
      induced by inelastic energy deposition events and mediated via highly excited
      vibrational states, may provide a pathway of fast local chromatin denaturation,
      thereby producing the severe DNA lesion able to interact chemically with other,
      non-damaged chromatin.

PMID- 12194280
TI  - Insights into the sites of X ray and neutron induced chromosomal aberrations in
      human lymphocytes using COBRA-MFISH.
AB  - A multi-colour fluorescence in situ hybridisation (MFISH) assay has been
      developed, for simultaneous visualisation of all human chromosomes in 24
      different colours. This assay is based on the simultaneous use of combinatorial
      labelling and ratio labelling, the so called combined binary ratio labelling
      (COBRA). This technique is used to study the spectra of chromosomal exchanges
      induced by X ray and neutrons in human lymphocytes. With X rays the dose-effect
      relationships for both dicentrics and translocations were linear-quadratic,
      whereas with neutrons these were linear. Among aberrant cells, average estimates
      of the minimum number of breaks was higher for neutrons than for X rays.
      Moreover, the induced chromosomal exchange patterns were more complex following
      neutron irradiation in comparison with X rays. COBRA-MFISH was found to have a
      greater resolving power over partial labelling for the accurate detection of
      complex translocations and insertions. With neutrons the frequencies of both were
      higher than those induced by X rays, and their relative proportions to the total
      frequencies were independent of dose. These data suggest insertions can be used
      as the 'signature' of high LET radiation.

PMID- 12194281
TI  - Intrachromosomal exchange aberrations predicted on the basis of the globular
      interphase chromosome model.
AB  - One of the key questions in understanding mechanisms of chromosome aberration
      production is how does interphase chromosome structure affect aberration
      formation. To explore this a modelling approach is presented which combines Monte
      Carlo simulation of both alpha particle track and interphase chromosome
      structure. The structural state of interphase chromosome influences a dose-effect
      relationship for intrachromosomal exchange aberrations (intrachanges). It is
      shown that intrachanges are induced frequently by both X rays and alpha particles
      if the chromosome is in the condensed globular but not in the decondensed coiled
      state. Truly simple intra-arm intrachanges induced by X rays are dose squared in
      coiled chromosomes, but exhibit linear dose dependence in globular chromosomes.
      Experimental data on interarm intrachanges obtained by dual arm chromosome
      painting are analysed by means of the technique presented. Results of analysis
      support the conclusion about the arms proximity of chromosome 1 in human
      lymphocytes.

PMID- 12194282
TI  - Cell cycle perturbations and cytogenetic damage induced by low energy protons in
      human primary fibroblasts.
AB  - Endpoints related to cell cycle perturbations were investigated in human primary
      fibroblasts irradiated with 1-4 Gy of either protons (7.7 and 28.5 keV.micron-1)
      or X rays. Regardless of the quality of radiation, 8 h after irradiation cells
      accumulated in the G2 phase, but such accumulation was maintained at 24 h from
      treatment only in 28.5 keV.micron-1 protons. A marked G1/S-transition block was
      observed in proton as well as in X ray-treated cultures up to 24 h, with doses as
      low as 1 Gy. On the other hand, the number of cells positive to p21 antibody
      reaction was higher after proton than after X ray treatment, indicating that the
      'complexity' of lesions may play a critical role in the induction of p21.

PMID- 12194283
TI  - Inactivation cross sections for mammalian cells exposed to charged particles: a
      phenomenological approach.
AB  - Published data on inactivation of V79 cells irradiated with monoenergetic proton
      and ion beams (He, C, O, Ne) have been analysed. Values for RBE alpha, RBE10% and
      the inactivation cross section sigma have been evaluated in the LET range between
      5 and 400 keV.micron-1. RBE against LET curves and inactivation cross sections
      against LET and against Z*2/beta 2 curves have been studied in a comparative
      approach with respect to the different ion types. RBE-LET curves depend strongly
      on the type of ion for LET > 30 keV.micron-1. At LET < 30 keV.micron-1 and low
      doses protons show the greatest effectiveness; at LET > 30 keV.micron-1 and high
      doses He ions provide the most effective radiation. Apart from protons,
      separation among the various ion curves is less marked in the sigma against
      Z*2/beta 2 plot than in the sigma against LET plot. sigma against Z*2/beta 2
      curves for ions with 2 < or = Z < or = 10 and 200 < Z*2/beta 2 < 1500 show a
      common trend independent of Z and are well represented by a linear relationship.

PMID- 12194284
TI  - Monte Carlo simulation of DNA damage by low LET radiation using inhomogeneous
      higher order DNA targets.
AB  - To test possible effects of the heterogeneous nature of the cell nucleus on
      simulation results of radiation-induced DNA damage, inhomogeneous targets have
      been implemented in the biophysical code PARTRAC. The geometry of the DNA and the
      histones was defined by spheres around the constituent atoms. Electron cross
      sections in liquid water were scaled according to the mass density of the
      different materials, whereas photon cross sections were derived from the sum of
      the cross sections for the constituent atoms. In the case of higher energy
      electrons the simulations show an increase of energy deposition in the DNA
      proportional to its high mass density. For photons with energies in the range of
      the carbon and the oxygen K-shell (0.28-0.53 keV), cross sections of DNA are
      larger than those of water, leading to an increased yield of strand breaks per
      average absorbed dose in the cell nucleus.

PMID- 12194285
TI  - Minisatellite and HPRT mutations in V79 and human cells irradiated with gamma
      rays.
AB  - The induction of mutations at the Hprt locus and minisatellite sequences was
      studied in V79 cells, peripheral blood lymphocytes (PBL) and lymphoblastoid cells
      (CCRF-CEM) exposed to gamma rays. In V79 cells the Hprt mutant frequency
      increased with dose at least up to 6.0 Gy, whereas the number of HPRT mutant
      lymphocytes increased up to 3 Gy. Clones derived from single irradiated cells
      were screened for mutations at minisatellite sequences by DNA fingerprint
      analysis. In V79 cells, a dose-response curve for minisatellite alterations was
      obtained up to 4.5 Gy. In contrast, very few mutations at minisatellite sequences
      (2/137) were detected among clones isolated from PBL of two donors irradiated
      with 1-4 Gy. Similar results were observed in lymphoblastoid CCRF-CEM cells
      irradiated with 2-3 Gy (4 mutants/180 clones), suggesting that in human lymphoid
      cells minisatellite DNA is more stable than in other mammalian and human cell
      lines.

PMID- 12194286
TI  - Relative biological effectiveness of light ions in human tumoural cell lines:
      role of protein p53.
AB  - Protons and alpha particles of high linear energy transfer (LET) have shown an
      increased relative biological effectiveness (RBE) with respect to X/gamma rays
      for several cellular and molecular endpoints in different in vitro cell systems.
      To contribute to understanding the biochemical mechanisms involved in the
      increased effectiveness of high LET radiation, an extensive study has been
      designed. The present work reports the preliminary result of this study on two
      human tumoural cell lines, DLD1 and HCT116, (with different p53 status), which
      indicate that for these cell lines, p53 does not appear to take a part in the
      response to radiation induced DNA damage, suggesting an alternative p53
      independent pathway and a cell biochemical mechanism dependent on the cell type.

PMID- 12194287
TI  - Incomplete chromosome exchanges are not fingerprints of high LET neutrons.
AB  - A new fluorescence in situ hybridisation (FISH) technique combining whole
      chromosome specific DNA libraries with pan-centromeric DNA and telomeric PNA
      probes was introduced to investigate the induction of chromosome exchanges in
      human lymphocytes after exposure to low (4 Gy X rays) and high (1 Gy neutrons)
      linear energy transfer radiation. This combination of probes allowed accurate
      detection of exchange aberrations involving the painted chromosomes and an
      unambiguous discrimination between complete and incomplete exchanges, as well as
      terminal and interstitial deletions. Data obtained in the present study using
      combined FISH assay with telomeres detection showed no differences between two
      types of radiation regarding the induction of incomplete exchanges.

PMID- 12194288
TI  - Biophysical study of the globular organisation of interphase chromosomes.
AB  - The globular model of interphase chromosomes is studied using methods involving
      the statistical physics of polymers. An interphase chromatid is represented as a
      flexible chain of structural sub-units, or superdomains (SDs). Each SD is
      simulated as a number of chromatin fibre loops fixed at a nuclear matrix core. A
      chain of SDs is further folded in the nucleus in a compact conformation owing to
      volumetric interactions between SDs. The algorithm used is extended to
      incorporate the chain anchorage at different points. Excluded volume effects are
      taken into account in Monte Carlo simulation at both the SD and whole chromosome
      level. A variety of structures is observed in computer experiments. The
      simulation results correlate with the available experimental data.

PMID- 12194289
TI  - Induction of micronuclei in a rat alveolar epithelial cell line by alpha particle
      irradiation.
AB  - Dose-response relationships for the induction of micronuclei were characterised
      in the rat alveolar epithelial cell line (SV40T2) exposed to either alpha
      particles(241Am: 3.2 MeV, 128 keV.micron-1, 0.093 Gy.min-1 at the cell-Mylar
      interface) or X rays (200 kVp, 1 Gy.min-1). The frequency of micronucleus
      formation was 1.6-3.0% for unirradiated subjects but increased for irradiated
      ones in a dose-dependent manner. A linear relationship between the dose and the
      micronucleus formation was observed until 1 Gy for alpha particles and 4 Gy for X
      rays. The linear slope for alpha particles was 28.5% per Gy and the relative
      biological effectiveness (RBE) was 4.3, as calculated from the slopes. The slope
      for alpha particles was dependent on the energy of the alpha particles. These
      results indicate that the micronucleus assay is available for biodosimetry of
      alpha particle irradiation in the rat alveolar epithelial cells, although
      consideration should be given to the range of the linearity and the LET of alpha
      particles.

PMID- 12194290
TI  - Non-targeted effects of radiation: bystander responses in cell and tissue models.
AB  - The standard paradigm for radiation effects in cellular systems has involved
      direct damage to DNA and in particular, DNA double strand breaks as the
      triggering lesions leading to mutation, cell death and transformation. Recently,
      however, a growing body of evidence has reported non-targeted effects, which are
      not a direct consequence of the initial lesions produced in cellular DNA. These
      have included bystander responses, genomic instability, gene induction, adaptive
      responses and low dose hypersensitivity. A common observation of these responses
      is that they dominate at low doses and saturate with increasing dose. Non
      targeted effects may therefore have consequences for extrapolation of risk
      estimates to low doses if these are important in vivo. A range of experimental
      techniques is being used to study non-targeted responses, including microbeam
      approaches. Microbeams have considerable advantages in that they allow individual
      cells and subcellular targets to be selected within populations with precise low
      doses and, if required, exact dose rates. Recent advances also allow targeting of
      3-D cell systems. The mechanisms underlying non-targeted responses appear to
      involve production of reactive oxygen species and direct cell-to-cell signalling
      via gap junctional intercellular communication although significant differences
      exist in different cell types. The triggering lesions for these responses remain
      unclear however. Some non-targeted responses may be inter-related, for example in
      the case of bystander responses and instability and may be part of a general
      stress response system in irradiated populations. Some non-targeted effects may
      also act as protective mechanisms; if they lead to the removal of potentially
      damaged cells from the population.

PMID- 12194292
TI  - Cross section calculations in condensed media: charged particles in liquid water.
AB  - Ionisation cross sections for charged particles are deduced within the framework
      of the relativistic plane wave first Born approximation and the classical
      electromagnetic theory. The macroscopic dielectric response function is related
      to the atomic generalised oscillator strength. Interaction cross sections for
      proton impact on liquid water are presented and discussed. A semi-empirical model
      for the angular distribution of secondary electrons produced by proton impact on
      liquid water, which is based on the Bethe approach, is presented.

PMID- 12194291
TI  - Genotoxic damage in non-irradiated cells: contribution from the bystander effect.
AB  - It has always been accepted dogma that the deleterious effects of ionising
      radiation such as mutagenesis and carcinogenesis are due mainly to direct damage
      to DNA. Using the Columbia University charged-particle microbeam and the highly
      sensitive AL cell mutagenic assay, it is shown here that non-irradiated cells
      acquire the mutagenic phenotype through direct contact with cells whose nuclei
      are traversed with 2 alpha particles each. Pre-treatment of cells with lindane, a
      gap junction inhibitor, significantly decreased the mutant yield. Furthermore,
      when irradiated cells were mixed with control cells in a similar ratio as the in
      situ studies, no enhancement in bystander mutagenesis was detected. Our studies
      provide clear evidence that genotoxic damage can be induced in non-irradiated
      cells, and that gap junction mediated cell-cell communication plays a critical
      role in the bystander phenomenon.

PMID- 12194293
TI  - Novel approaches with track segment alpha particles and cell co-cultures in
      studies of bystander effects.
AB  - There is now a significant body of data that indicate that the effects of
      ionising radiation may extend to more than those cells that directly suffer
      damage to DNA in the cell nucleus. Cells neighbouring those cells that are
      irradiated, or even well separated from those that are irradiated demonstrate
      several responses that are recorded in hit cells as a function of absorbed dose.
      That is, the responding non-hit cells are bystanders of hit cells. A protocol has
      been devised which allows for examination of one means of eliciting bystander
      responses, specifically, effects on non-contacting cells. Cell culture chambers
      are set up such that a population of cells is physically separate from the energy
      depositions of track segment charged particles. Absorption of energy in sub
      millimetre distances in the cell culture medium ensures that one population of
      cells can only respond to factors generated in the irradiated medium or in
      another population of irradiated co-cultured cells, which may be of similar or
      dissimilar origin. For irradiation of medium alone, enhanced levels of
      micronuclei, and of delays in cell cycle progression occur in normal human
      fibroblasts, but not epithelial cells. This procedure allows for a defining of
      the factors responsible for initiating bystander effects and for determining
      their quantitative relevance.

PMID- 12194294
TI  - Radiosensitivity of V79 cells after alpha particle radiation at low doses.
AB  - Low dose hyper-radiosensitivity (HRS) of V79 cells was demonstrated after
      irradiation with gamma rays and 4He2+ ions of various linear energy transfer
      (LET) values (58.9, 79.3 and 101.7 keV.micron-1). In parallel, the cytogenetic
      analysis showed an LET dependence of aberrations at a dose of 1 Gy, while the
      observed chromatid fragments appeared to vary with the number of 4He2+ ions
      traversing the cell nucleus. The results of both studies are correlated so as to
      achieve a better understanding of the so-called induced radioresistance. The cell
      mechanism of radioresistance appears to be induced after a certain amount of
      energy is deposited in the cell nucleus. This amount depends both on the
      radiation quality as well as the number of particles traversing the cell,
      inducing chromosome alterations and chromatid damage.

PMID- 12194295
TI  - Mutation induction in human cells after low dose X ray exposure.
AB  - Mutations induced after low dose ionising radiation exposure have been
      intensively analysed not only for radiation risk estimation but also for basic
      understanding of cellular responses. Human lymphoblastoid TK6-20C cells were
      irradiated with 100 mGy of X rays and mutation at the heterozygous thymidine
      kinase (TK) locus was selected by trifluorothymidine (TFT) resistance. Although
      the mutation frequency at the TK locus increased from 5.6 x 10(-6) to 7.4 x 10(
      6), this increase was not statistically significant. However, molecular analysis
      of TK mutants exhibiting loss of heterozygocity (LOH) demonstrated a clear effect
      of such low dose IR exposure. Exposure to 100 mGy X ray increased the fraction of
      hemizygous-LOH from 10% to 42%. In previous experiments, a similar tendency in
      the increase of hemizygous-LOH was also observed in TK6 cells after exposure to a
      2 Gy dose of X rays. This type of LOH can be considered as a result of end
      joining repair of DNA double strand breaks.

PMID- 12194296
TI  - Induction of chromosome aberrations is non-linear within the low dose region and
      depends on dose rate.
AB  - The low dose region was evaluated for meristem cells of spring barley. A study of
      the cytogenetic damage in the low dose range was carried out to determine the
      genuine shape of the dose curve. The relationship between the frequency of
      aberrant cells and the absorbed dose is shown to be non-linear with a site at low
      doses within which the cytogenetic damage exceeds the control level significantly
      and does not depend on dose value. Within the tested exposure region, the
      aberrant cell frequency is found to decrease with increasing dose rate, but the
      shape of the dose curve remained invariable. The piecewise linear model fits the
      experimental data much better than the linear one.

PMID- 12194297
TI  - Bystander-induced apoptosis and premature differentiation in primary urothelial
      explants after charged particle microbeam irradiation.
AB  - The ureter primary explant technique was developed to study bystander effects
      under in vivo like conditions where stem and differentiated cells are present.
      Irradiation was performed with a 3He2+ charged particle microbeam available at
      the Gray Cancer Institute, with high (approximately 2 microns) precision. Tissue
      sections from porcine ureters were pre-irradiated with the microbeam at a single
      location with 10 3He2+ particles (5 MeV; LET 70 keV.micron-1). After irradiation,
      the tissue section was incubated for 7 days, thus allowing the explant outgrowth
      to form. Total cellular damage (total fraction of micronucleated and apoptotic
      cells) was measured according to morphological criteria. Apoptosis was also
      assessed using a 3'-OH DNA end-labelling technique. Premature differentiation was
      estimated using antibodies to uroplakin III, a specific marker of terminal
      urothelial differentiation. Results of our experiments demonstrated a significant
      bystander-induced differentiation and a less significant increase in apoptotic
      and micronucleated cells. A hypothesis based on the protective nature of the
      bystander effect is proposed.

PMID- 12194298
TI  - Cellular responses to low dose heavy-ion exposure in human cells.
AB  - The human lymphoblastoid cell line TK6 was used to study the cellular responses
      after low-dose (100, 200, 500 mGy) or high-dose (3 Gy) of X rays, C (22
      keV.micron-1) and Fe (1000 keV.micron-1) ion exposures. p53 protein induction in
      individual cells was determined by indirect immunofluorescence staining. Cell
      cycle progression after heavy-ion exposure was determined by using a laser
      scanning cytometer. A characteristic pattern of cell-cycle progression was
      observed with 3 Gy exposure of Fe ions but not with 100 mGy. Similarly such a
      pattern with 100 mGy C ion exposure did not match that with 3 Gy. The proportion
      of p53-induced cells is proportional to the probability of cell being hit by a
      primary heavy ion. The observed low-dose effect can be reflected in the
      probability of a hit, although detailed nature about their energy deposition must
      be considered for more precise estimation of such an effect. New detection
      methodology must be developed for identification of heavy-ion specific cellular
      responses.

PMID- 12194299
TI  - Low dose hypersensitivity and induced resistance of V79 cells after charged
      particle irradiation using 100 MeV/u carbon ions.
AB  - This work aimed to study the effects of low dose irradiation in order to detect
      possible deviations from the linear-quadratic dose dependence of survival after
      charged particle irradiation. Survival of V79 cells at low doses was studied
      using a semi-automated cell detection system similar to the DMIPS system. With
      such a technique, the precision of survival measurements is improved by avoiding
      the stochastic uncertainties of the conventional dilution assay. A significant
      hypersensitivity at low doses (0.1 Gy) has been detected for 100 MeV/u carbon
      ions, whereas for higher doses (up to 0.5 Gy) a transition to a plateau-like
      region is observed, which is consistent with the assumption of induced
      resistance. These results are apparently in contrast to earlier studies using
      high-LET radiation like, e.g. neutrons or negative pions, where the effect of
      induced resistance has been reported to be at least significantly reduced for
      single exposure experiments.

PMID- 12194300
TI  - The genetics of radiation-induced osteosarcoma.
AB  - Individual genetic variation can influence susceptibility to the carcinogenic
      effects of many environmental carcinogens. In radiation-exposed populations those
      individuals with a greater genetically determined susceptibility would be at
      greater risk of developing cancer. To include this modification of risk into
      radiation protection schemes it is necessary to identify the genes responsible
      for determining individual sensitivity. Alpha-particle-induced osteosarcoma in
      the mouse has been adopted as a model of human radiation carcinogenesis, and
      genome-wide screens have been conducted for allelic imbalance and genetic
      linkage. These studies have revealed a series of genes involved in determining
      the sensitivity to radiogenic osteosarcoma formation.

PMID- 12194301
TI  - Enhanced mutation and neoplastic transformation in human cells by 29 kVp relative
      to 200 kVp X rays indicating a strong dependence of RBE on photon energy.
AB  - The fundamental assumption implicit in the use of the atomic bomb survivor data
      to derive risk estimates for occupational and medical exposures is that the gamma
      rays of Hiroshima and Nagasaki are considered as equal efficiencies to other low
      LET radiations up to an LET of 10 keV.micron-1. For breast cancer induction,
      neoplastic cell transformation, mutation, reciprocal translocations and
      dicentrics in human lymphocytes, a strong and very similar dependence of the RBE
      values on photon energy or on LET is observed. Experimental data on mutation
      induction and neoplastic cell transformation in human cells show that 29 kVp X
      rays are by a factor of 4 and 3.4, respectively, more effective compared with 200
      kVp X rays. These data are in excellent agreement with the data in the
      literature.

PMID- 12194302
TI  - Implications of the analysis of epidemiological data using a two-mutation
      carcinogenesis model for radiation risks.
AB  - A two-mutation carcinogenesis (TMC) model is used as a bridge between cellular
      radiation biological effects and the incidence of cancer. This model has been
      applied to several sets of experimental animal and epidemiological data. In this
      paper the advantage of the model and the implications for radiation risks at low
      doses are discussed with respect to the age and dose dependence of cancer
      incidence and the effect of age at exposure on radiation risk; the link between
      the radiation effect and background cancer incidence and the transfer of
      radiation risk across different population groups; the implications of acute and
      protracted radiation exposures for risks at low doses and the dose-effect
      relationship for radium induced bone cancer.

PMID- 12194303
TI  - DNA double strand break induction in yeast.
AB  - The induction of DNA double strand breaks (DSBs) by accelerated heavy ions was
      systematically measured in diploid yeast cells. Particles were provided by the
      accelerators at GSI, Darmstadt, and HMI, Berlin. DNA was separated using pulsed
      field gel electrophoresis and the intensity of the largest bands used to
      determine the loss of molecular weight. Since the DNA content of each chromosome
      is exactly known absolute values for DSB induction can be measured without
      calibration procedures. Ions used range from protons to uranium with LET values
      between 2 and about 15,000 keV.micron-1. Induction cross sections increase in the
      lower LET region approaching a plateau around 200 keV.micron-1. With higher LET
      values the dependence can no longer be described by a common curve with each ion
      showing a specific behaviour. With very heavy particles the influence of the
      penumbra becomes obvious: cross sections decrease with LET because of the reduced
      penumbra extensions. Classical target theory would predict cross sections to
      follow a simple saturation function which is not substantiated by the data. Track
      structure analysis as introduced by Butts and Katz in 1967 is also not able to
      predict the experimental results. A semi-empirical fit indicates a linear
      quadratic dependence of induction cross sections on LET up to about 1000
      keV.micron-1. RBE for DSB induction rises above unity reaching a maximum of about
      2.5 around 200 keV.micron-1. This is different from many experiments in mammalian
      cells and is presumably due to differences in chromatin structure since yeast
      cells seem to lack a functional III histone.

PMID- 12194304
TI  - Lower radiation weighting factor for radon indicated in mechanistic modelling of
      human lung cancer.
AB  - A two-mutation carcinogenesis (TMC) model was fitted to the age-dependent lung
      cancer incidence in a cohort of Dutch Hodgkin patients treated with radiotherapy.
      Employing the results of previous TMC analyses of lung cancer due to smoking (by
      British doctors) and due to exposure to radon (for Colorado miners) a model fit
      was obtained with an estimate for the low LET radiation effect at the cellular
      level. This allows risk calculations for lung cancer from low LET radiation. The
      excess absolute risks are in tune with the values reported in the literature, the
      excess relative risks differ among the exposed groups. Comparing the cellular
      radiation coefficients for radon and for low LET radiation leads to an estimated
      radiation weighting factor for radon of 3 (0.1-6).

PMID- 12194305
TI  - Observation of radiation-specific damage in human cells exposed to depleted
      uranium: dicentric frequency and neoplastic transformation as endpoints.
AB  - Depleted uranium (DU) is a dense heavy metal used primarily in military
      applications. Published data from our laboratory have demonstrated that DU
      exposure in vitro to immortalised human osteoblast cells (HOS) is both
      neoplastically transforming and genotoxic. DU possesses both a radiological
      (alpha-particle) and chemical (metal) component. Since DU has a low specific
      activity in comparison to natural uranium, it is not considered to be a
      significant radiological hazard. The potential contribution of radiation to DU
      induced biological effects is unknown and the involvement of radiation in DU
      induced biological effects could have significant implications for current risk
      estimates for internalised DU exposure. Two approaches were used to address this
      question. The frequency of dicentrics was measured in HOS cells following DU
      exposure in vitro. Data demonstrated that DU exposure (50 microM, 24 h) induced a
      significant elevation in dicentric frequency in vitro in contrast to incubation
      with the heavy metals, nickel and tungsten which did not increase dicentric
      frequency above background levels. Using the same concentration (50 microM) of
      three uranyl nitrate compounds that have different uranium isotopic
      concentrations and therefore, different specific activities, the effect on
      neoplastic transformation in vitro was examined. HOS cells were exposed to one of
      three-uranyl nitrate compounds (238U-uranyl nitrate, specific activity 0.33
      microCi.g-1; DU-uranyl nitrate, specific activity 0.44 microCi.g-1; and 235U
      uranyl nitrate, specific activity 2.2 microCi.g-1) delivered at a concentration
      of 50 microM for 24 h. Results showed, at equal uranium concentration, there was
      a specific activity dependent increase in neoplastic transformation frequency.
      Taken together these data suggest that radiation can play a role in DU-induced
      biological effects in vitro.

PMID- 12194306
TI  - Possible implications of non-linear radiobiological effects for the estimation of
      radiation risk at low doses.
AB  - Possible implications of the effects of low LET radiation on the induction of
      cancer at low doses are studied. Low dose hypersensitivity and adaptive response
      were identified as candidates which may give a non-linear dose effect curve for
      acute exposures, whereas adaptive response may influence protracted exposures. In
      this paper acute exposures are studied. Several radiobiological reports on
      studies with mammalian cell lines have indicated the presence of a hypersensitive
      region in the radiation survival response at low doses followed by an increase in
      radioresistance. The two step clonal expansion (TSCE) model for the process of
      carcinogenesis was adapted in such a way that cell killing after acute radiation
      induces increased clonal expansion for some time and thus gives a promoting
      effect of radiation. As a first step, the Radiation Effects Research Foundation
      (RERF) data on the lung cancer incidence are fitted to study how such a model
      would influence the assessment of the cancer risk at low doses.

PMID- 12194307
TI  - Microbeams: a potent mix of physics and biology. Summary of the 5th International
      Workshop on Microbeam Probes of Cellular Radiation Response.
AB  - Single-cell microbeam irradiators are of increasing interest to the biological
      community. The 5th International Workshop on Microbeam Probes of Cellular
      Radiation Response, which took place in Stresa, Italy, in May 2001, was attended
      by about 120 registrants, roughly evenly divided between physicists and
      biologists. Many new microbeam devices are now under development, and there has
      been a significant diversification of the biological questions addressed. Most
      current uses of microbeams have been to address radiobiological questions, but
      the advent of sub-micrometre targeting capabilities, and the development of new
      single-cell assays, point to the potential for microbeams to make an important
      contribution to biological, and not just radiobiological, studies.

PMID- 12194308
TI  - Upgrading of the Gray Laboratory soft X ray microprobe and V79 survival
      measurements following irradiation of one or all cells with a CK X ray beam of
      different size.
AB  - The X ray microprobe developed at the Gray Laboratory was originally designed to
      produce carbon K X rays (278 eV) by electron bombardment and focus them to a few
      hundred nanometers spot by using a circular diffraction grating with increasing
      line density (zone plate). The very fine focus achieved (< 0.25 micron radius
      spot) and the highly localised energy deposition of CK X rays (photoelectron
      range < 7 nm), represent unique tools to investigate modern radiobiological
      phenomena. Recent improvements have been directed to increase the dose rate (up
      to approximately 6 Gy.s-1 entrance dose averaged over a typical V79 cell) and to
      evaluate the possibility of using higher energy photons (AlK of 1.48 keV). The
      efficiency of the microprobe system has been tested by assessing the clonogenic
      potential of V79 cells irradiated with CK X ray beams of different sizes (5 and
      0.25 microns radius) and investigating the relevance of the spatial distribution
      of cells for the bystander effect.

PMID- 12194309
TI  - Development of the large scale digital cell analysis system.
AB  - Quantitative analysis of large numbers of cells exposed to various stresses would
      be facilitated by an automated microscope system designed to monitor up to 1000
      microscope fields over time intervals of up to one month. The Large Scale Digital
      Cell Analysis System (LSDCAS) was designed by the authors to provide such
      analysis capabilities. This report presents a description of the development of
      the LSDCAS and its application to the study of cells undergoing radiation-induced
      mitotic catastrophe. A detailed description of the data acquisition algorithms
      used and the hardware configuration underlying the system is presented.
      Quantitative analysis of colony formation of cells exposed to 5 Gy X irradiation
      is presented. Upon analysis, it was found that the plating efficiency in
      irradiated populations agreed with that obtained using conventional colony
      formation assays, indicating the accuracy of LSDCAS in the determination of cell
      clonogenicity. An unexpected finding was that fully 50% of the surviving colonies
      exhibited mitotic catastrophe that persisted throughout colony formation. Ongoing
      extension of the capabilities of the LSDCAS using image segmentation techniques
      applied to a variety of cellular endpoints is then briefly described.

PMID- 12194310
TI  - Nuclear reactions in Monte Carlo codes.
AB  - The physics foundations of hadronic interactions as implemented in most Monte
      Carlo codes are presented together with a few practical examples. The description
      of the relevant physics is presented schematically split into the major steps in
      order to stress the different approaches required for the full understanding of
      nuclear reactions at intermediate and high energies. Due to the complexity of the
      problem, only a few semi-qualitative arguments are developed in this paper. The
      description will be necessarily schematic and somewhat incomplete, but hopefully
      it will be useful for a first introduction into this topic. Examples are shown
      mostly for the high energy regime, where all mechanisms mentioned in the paper
      are at work and to which perhaps most of the readers are less accustomed.
      Examples for lower energies can be found in the references.

PMID- 12194311
TI  - Proto-oncogene expression: a predictive assay for radiation biodosimetry
      applications.
AB  - Using a model system of in vitro human peripheral blood lymphocytes, the effect
      of low-dose (0.25 to 1.50 Gy) 250-kVp X ray radiation (1 Gy.min-1) on the
      expression of several proto-oncogenes was examined (c-Haras, c-src, c-met, c-jun,
      c-fos, and c-myc) and beta-actin from 0.25 to 17 h post-radiation. RNA was
      extracted from cells harvested at various times after exposure and examined for
      levels of particular mRNAs by northern blot hybridisation. A progressive time-
      and dose-dependent increase in mRNA levels was observed for c-Haras mRNA, while
      the other proto-oncogenes (c-src, c-met, c-fos, c-jun and c-myc) examined were
      variable during the same time period. beta-actin levels were initially decreased
      but at 17 h post-radiation had returned to control levels. A comparison of the
      rate of c-Haras transcription at 5 and 17 h post-irradiation revealed that c
      Haras transcription was higher at 5 h than at 17 h. These findings suggest that
      the level of specific proto-oncogene expression, particularly c-Haras, may be
      useful early diagnostic molecular biomarkers for biodosimetry applications. The
      use of real-time PCR technologies to quantify gene expression changes will also
      be discussed.

PMID- 12194312
TI  - A bio-dosemeter that utilises isolated enzymes to detect ionising radiation.
AB  - The development of a biosensor for the detection of ionising radiation
      (biodosemeter) utilising the advantageous properties of the photosystem II (PSII)
      complex and its response to ionising radiation is reported. The transducer signal
      for this biosensor can be fluorescence, which is dependent on photosynthetic
      activity. Exposure of biological material to ionising radiation leads to a loss
      of function due to the destruction of critical structures. Radiation target
      theory predicts an exponential decrease in biochemical activity that is dependent
      on the absorbed radiation energy and directly proportional to the mass of the
      individual molecules possessing this activity. The activity is lost whenever the
      protein is hit since very high energy is transferred through the chain. Several
      approaches were used to optimise the immobilisation of PSII complexes to improve
      the sensitivity of the bio-dosemeter.

PMID- 12194313
TI  - Changes in soluble metabolites induced in tumour cells by gamma rays and proton
      beams: a 1H magnetic resonance spectroscopy study.
AB  - Cultured HeLa cells have been irradiated with a single acute dose of either gamma
      rays (40 Gy) or low energy proton beams (20 Gy). 1H magnetic resonance spectra of
      perchloric acid extracts (PCA) prepared at different times after irradiation show
      an intensity decrease of signal from glutathione and a parallel increase of
      lactate signal. Intensity ratios of signals of glycerophosphorylcholine to that
      of phosphorylcholine increase with time after irradiation. Irradiating cells with
      gamma rays or proton beams at half a dose obtain effects of comparable extent.
      The present experiments indicate that relevant metabolic alterations take place
      in cells damaged by irradiation. Finally, these data represent a first indication
      that the relative biological efficiency of low energy proton beams with respect
      to gamma rays can reach a value of 2 as evidenced by cell metabolic impairment.

PMID- 12194314
TI  - Classical microdosimetry in radiation protection dosimetry and monitoring.
AB  - Classical microdosimetry concerns the measurement and analysis of the spectrum of
      radiation energy deposition events in simulated microscopic tissue-equivalent
      sites. Over the past three decades, classical microdosimetry has been extensively
      applied for the direct measurement of dosimetric quantities, such as the ambient
      dose equivalent, and for the spectroscopic properties of tissue-equivalent
      proportional counters that have led to methods of mixed-field analysis and
      particle identification. This paper reviews some of the special applications of
      classical microdosimetry such as the determination of kerma coefficients,
      differential dosimetry and aviation dosimetry. Also reviewed are some of the
      technological innovations related to the application of microdosimetry in
      operational health physics and in particular the development of multi-element
      proportional counters and detectors based on gas microstrip technology.

PMID- 12194315
TI  - Experimental tools for track structure investigations: new approaches for
      dosimetry and microdosimetry.
AB  - In recent years, several new methods have been developed for track structure
      investigations. They use macroscopic gas volumes to transfer the results to
      microscopic dimensions and are based on either the cluster counting principle or
      on optical methods for full track analysis. The first type of method allows
      cluster size distributions in nanometre dimensions to be measured. The second
      type reveals the full topology of the ionisation pattern of tracks or track
      segments within a volume of a few micrometres with a spatial resolution down to 5
      nm. The basic principles of these instruments and their main features are
      summarised and a selection of results obtained to date are shown.

PMID- 12194316
TI  - Wall-less ion-counting nanodosimetry applied to protons.
AB  - A wall-less ion-counting nanodosemeter, conceived for precise ionisation-cluster
      measurements in an accelerator environment, is described. The technique provides
      an accurate means for counting single radiation-induced ions, in dilute gas
      models of condensed matter. The sensitive volume dimensions, a few tissue
      equivalent nm in diameter by a few tens of nm, are tunable by a proper choice of
      the gas pressure and electric fields; nanometric sub-sections can be
      electronically selected. Detailed ion-cluster distributions are presented for
      protons of 7.15, 13.6 and 19.3 MeV, in biologically relevant DNA-like sensitive
      volumes of low-pressure propane. Experimental results are compared to model
      simulations.

PMID- 12194318
TI  - Nanodosimetric measurements with an avalanche confinement TEPC.
AB  - This paper illustrates a tissue-equivalent proportional counter designed to have
      high gas gain and good energy resolution at nanometric simulated site sizes.
      Microdosimetric neutron and gamma spectra were measured in dimethyl ether and in
      propane-based tissue-equivalent gas mixture down to 35 nm. The comparison of
      experimental data with the results of Monte Carlo calculations shows a
      satisfactory agreement.

PMID- 12194317
TI  - The formation of ionisation clusters by alpha particles in 'nanometric' volumes
      of nitrogen: experiment and calculation.
AB  - Probability distributions of the size of ion clusters created in 'nanometric'
      cylindrical volumes of nitrogen by single 4.6 MeV alpha particles were measured
      and compared with those calculated by Monte Carlo simulation. The diameter of the
      sensitive volume had a mass per area of between 0.015 and 1.3 micrograms.cm-2
      which, for a material at unit density, corresponds to a diameter of between 0.15
      nm and 13 nm. These nanometre sizes were simulated experimentally in a device
      called Jet Counter. The measured or calculated cluster size probabilities
      confirmed that the formation of ionisation clusters along a 'nanometre' track can
      be characterised by Poisson's distribution only for very small targets. The
      present ionisation cluster probabilities produced in 'nanometric' volumes, 2 to
      10 nm in diameter, are the first ever determined experimentally and confirmed by
      Monte Carlo simulation.

PMID- 12194319
TI  - A feasibility study of a single event spectrometer based on semiconductor
      devices.
AB  - The electronics employed around particle accelerators can be disturbed or damaged
      because of single event effects (SEE). The most likely effect is the single event
      upset (SEU) which may affect all memory devices. In the case of high energy
      accelerators, SEUs are mostly produced by secondary charged particles generated
      by neutron interactions. The measurement of the energy and the lineal energy
      distribution of these neutron-induced charged particles was proposed. As a first
      approach, a commercial p-i-n photodiode was employed. This device was irradiated
      with thermal and monoenergetic fast neutrons. Some effects limiting the use of
      such a detector as a SEE spectrometer were observed, giving guidelines for the
      design of an application specific integrated circuit (ASIC). The possibility of
      creating a solid state microdosemeter by coupling the ASIC with a tissue
      equivalent radiator is discussed. Moreover, the p-i-n photodiode covered with a
      hydrogenated plastic radiator may be employed as a proton-recoil spectrometer.

PMID- 12194320
TI  - Energy dependence of W values of protons in water.
AB  - The W values of protons in water vapour were measured for energies from 1 keV to
      100 keV with uncertainties lower than 1%. To study the energy and phase
      dependence of W values, the W values of protons in water vapour and liquid water
      were calculated for energies from 0.1 keV and 10 MeV and then compared to the
      experimental results of this work.

PMID- 12194321
TI  - Application of TEPC microdosimetry to boron neutron capture therapy.
AB  - Boron neutron capture therapy (BNCT) is a bimodal radiation therapy used
      primarily for highly malignant gliomas. Tissue-equivalent proportional counter
      (TEPC) microdosimetry has proven an ideal dosimetry technique for BNCT,
      facilitating accurate separation of the photon and neutron absorbed dose
      components, assessment of radiation quality and measurement of the BNC dose. A
      miniature dual-TEPC system has been constructed to facilitate microdosimetry
      measurements with excellent spatial resolution in high-flux clinical neutron
      capture therapy beams. A 10B-loaded TEPC allows direct measurement of the
      secondary charged particle spectrum resulting from the BNC reaction. A matching
      TEPC fabricated from brain-tissue-equivalent plastic allows evaluation of
      secondary charged particle spectra from photon and neutron interactions in normal
      brain tissue. Microdosimetric measurements performed in clinical BNCT beams using
      these novel miniature TEPCs are presented, and the advantages of this technique
      for such applications are discussed.

PMID- 12194322
TI  - Imaging of microscopic features of charged particle tracks in a low-pressure gas.
AB  - An imaging system for measuring the spatial distribution of charged particle
      tracks in a low-pressure gas is presented. The method is based on an optically
      read out time projection chamber. Results of experiments with fast heavy ions are
      shown.

PMID- 12194323
TI  - Track nanodosimetry of an alpha particle.
AB  - Experimental measurements and calculations are described of ionisation
      distributions in propane wall-less gas cavities of about 20 nm simulated size,
      performed at different distances from a 244Cm alpha particle track. Ionisation
      events are detected one by one by collecting electrons from the sensitive volume
      and by separating them with a drift column. Experimental results and Monte Carlo
      calculations indicate that, in the delta ray cloud, conditional probability
      curves, average cluster size and the ratio of second moment above first moment of
      the cluster distribution are invariant with track distance.

PMID- 12194324
TI  - Chemical bonds broken in latent tracks of light ions in plastic track detectors.
AB  - When a swift ion is slowed down through a plastic detector it creates a latent
      track. In nuclear track detectors, this latent track can be specifically etched
      by an appropriate chemical solution. This enlargement process is due to a higher
      etch velocity (VT) along the ion's path than in the non-damaged part of the
      detector. The etched track velocity is definitely linked to the damage created by
      the incoming ion in the detector material. A relationship between the physical
      parameters of the energy deposition and the variation in this etched track
      velocity with the ion energy cannot easily be explained. We present here our
      study on the chemical damage created by several ions in a cellulose nitrate type
      detector and our first attempt to simulate them by the use of the hit theory.

PMID- 12194325
TI  - Dose reconstruction in irradiated Fricke-agarose gels by means of MRI and optical
      techniques: 2D modelling of diffusion of ferric ions.
AB  - Fricke-agarose gels have elicited much interest in the field of radiation
      dosimetry, as tissue-equivalent dosemeters. magnetic resonance (MR) relaxation
      rates are measured for dose reconstruction. A major problem of Fricke-agarose
      gels is the diffusion of the ferric ions formed after irradiation. Knowledge of
      the diffusion coefficient of ferric ions may be necessary. Xylene orange, a dye
      that specifically chelates ferric ions, was added to the Fricke gel system to
      reduce ion diffusion and, as the binding gives a coloured complex, to allow
      optical detection of ferric ions. Diffusion of ferric ions in two dimensions and
      time evolution of ion concentration were evaluated. MR images were obtained at
      different times after irradiation. Ferric ion distribution, the corresponding
      images and the doses at different times after irradiation were reconstructed
      taking into account the calculated diffusion coefficients. Diffusion was then
      estimated by means of two different optical methods. The agreement obtained
      supports the reliability of the MRI method and of the model.

PMID- 12194326
TI  - Spatial variation of radiation quality during moving beam therapy with 14 MeV
      [d(0.25)+T] neutrons.
AB  - In conformal moving beam therapy with fast neutrons, the contributions to dose
      from the direct beam, scattered radiation and the gamma component vary with the
      position in the phantom. To determine this variation in radiation quality,
      microdosimetric measurements of energy deposition spectra were performed at
      different position in a therapy phantom. Fixed beam irradiation at different
      incidence angles showed strong changes in the lineal energy spectrum. An increase
      of slow protons (20 < y < 110 keV.micron-1) and a decrease of fast protons (2 < y
      < 20 keV.micron-1) was seen for irradiation outside the direct beam. During
      moving beam irradiation, different positions on the same isodose curves (55% or
      35%) showed differences in YD of up to 5%. Variations in the quality parameter,
      R, determined by applying an empirical biological weighting function, were of
      similar magnitude. Thus, spatial variations in radiation quality should be taken
      into account in biological dose planning for moving beam neutron therapy.

PMID- 12194327
TI  - MCNP modelling of the wall effects observed in tissue-equivalent proportional
      counters.
AB  - Tissue-equivalent proportional counters (TEPCs) utilise tissue-equivalent
      materials to depict homogeneous microscopic volumes of human tissue. Although
      both the walls and gas simulate the same medium, they respond to radiation
      differently. Density differences between the two materials cause distortions, or
      wall effects, in measurements, with the most dominant effect caused by delta
      rays. This study uses a Monte Carlo transport code, MCNP, to simulate the
      transport of secondary electrons within a TEPC. The Rudd model, a singly
      differential cross section with no dependence on electron direction, is used to
      describe the energy spectrum obtained by the impact of two iron beams on water.
      Based on the models used in this study, a wall-less TEPC had a higher lineal
      energy (keV.micron-1) as a function of impact parameter than a solid-wall TEPC
      for the iron beams under consideration. An important conclusion of this study is
      that MCNP has the ability to model the wall effects observed in TEPCs.

PMID- 12194328
TI  - Microscopic response of radiation on imaging plates.
AB  - The microscopic response of alpha particles on an imaging plate was studied
      experimentally. It is proved that a single alpha event can be discriminated from
      background signals and be recorded on the imaging plate. The spatial resolution
      of the dose distribution was found to be 43 +/- 2 microns when alpha particles
      were injected perpendicularly. The observed output signals are well described by
      the deposited energy.

PMID- 12194329
TI  - Response investigations of a TEPC in high energy proton and neutron beams using
      the variance method.
AB  - Results from measurements in proton and neutron beams between 68 and 174 MeV at
      the T. Svedberg Laboratory in Uppsala are presented. The result indicate that a
      TEPC might underestimate the high-energy contribution to H*(10) in cosmic
      radiation applications such as measurements onboard aircraft.

PMID- 12194330
TI  - Active neutron dosemeters based on microdosimetric principles: research studies.
AB  - Over the past few years, the Institute for Radiation Protection and Nuclear
      Safety (IRSN) has been studying a personal electronic neutron dosemeter and an
      ambient electronic neutron dosemeter based on experimental microdosimetric
      principles using low pressure proportional counters. The results obtained in 2000
      and in 2001 with the cylindrical tissue-equivalent proportional counter developed
      for use in radiation protection and filled with a low pressure tissue-equivalent
      gas (propane based) are presented here.

PMID- 12194331
TI  - A microdosimetry chamber for low-energy X rays.
AB  - A wall-less proportional counter designed to measure single event spectra
      produced by low energy X rays is described. The sensitive volume of the counter
      and the housing are made entirely of non-metallic materials to minimise
      distortions in the secondary electron spectrum.

PMID- 12194332
TI  - A practical design of a cylindrical tissue-equivalent proportional counter for
      microdosimetry.
AB  - A 12 mm tissue-equivalent proportional counter (TEPC) was designed, constructed
      and successfully tested. This detector achieves features common to others TEPCs,
      but it does not use field shaping electrodes and it is able to work at higher
      bias voltages which makes it capable of measuring the whole range of energy
      deposition events for gamma rays. The following approach was used to design the
      detector: first of all the use of a cylindrical shape detector featured as simple
      as possible but keeping its performance as well, the next point is to avoid the
      use of field shaping tubes and the last one is to make the preamplifier small and
      as close as possible to the detector. Its construction is based on a cylindrical
      proportional counter with A-150 tissue-equivalent material as cathode, TE-methane
      gas as a proportional gas and a 20 microns diameter wire as anode.

PMID- 12194333
TI  - Microdosimetric one hit detector model for calculation of dose and energy
      response of some solid state detectors.
AB  - A microdosimetric one hit detector model has been applied to calculate dose
      response, energy response and relative efficiency of thermoluminescent
      LiF:Mg,Cu,P (MCP-N), CaF2:Tm (TLD-300) and ESR alanine detectors on radiation of
      different qualities. For each detector type two model parameters, the target size
      and the saturation parameter, alpha, have been derived. Using those parameters
      and the microdosimetric distributions in nanometre size targets calculated using
      Monte Carlo track structure codes TRION and MOCA-14 it was possible to predict a
      great variety of experimental data for photons, X rays, beta electrons, protons,
      alpha particles and heavy ions. Due to a good reproducibility of experimental
      data some solid state detectors might be useful to test biophysical models of
      radiation action. Furthermore, these models can give some insight into the
      physics of radiation action in solid state detectors such as the range of charge
      interaction, energy levels etc.

PMID- 12194334
TI  - Microdosimetry of epithermal neutron field at the Kyoto University reactor.
AB  - Microdosimetric spectra were measured in order to gain the microdosimetric
      parameters of some epithermal neutron fields. Changes in dose mean lineal energy
      YD as a function of depth of heavy water showed a trend of softening with heavy
      water of the beam. The neutron absorbed dose was obtained by using the frequency
      mean lineal energy. Results show good agreement with measurements with the
      activation method using gold foil. This study demonstrated how microdosimetric
      parameters change in radiation quality as a function of heavy water depth.

PMID- 12194335
TI  - Ionisation clusters at DNA level: experimental modelling.
AB  - The importance of initial clustered damage to DNA is a hypothesis, which has to
      be approached also from physical modelling of the initial products of single
      charged particle interaction with DNA. A new tool for such studies, presented
      here, is based on modelling of the ionisation patterns resulting from a single
      charged particle crossing a nitrogen cavity of nanometre size. The nanometre size
      sites equivalent in unit density to DNA and nucleosome, have been modelled in a
      device, called a Jet Counter, consisting of a pulse operated valve which injects
      nitrogen in the form of an expansion jet into an interaction chamber. The
      distributions of the number of ions in a cluster created by a single alpha
      particle of 4.6 MeV along 0.15 nm to 13 nm size in nitrogen have been measured. A
      new descriptor of radiation action at DNA level is proposed.

PMID- 12194336
TI  - Semi-empirical inelastic cross sections for electron transport in liquid water.
AB  - Electron inelastic cross sections for water in the liquid phase are important for
      developing Monte Carlo codes that simulate the full degradation of any radiation
      beam in biological matter. The limited experimental information for condensed
      targets and the complexity of the background theory has led to largely heuristic
      semi-empirical models. The present work makes use of the dielectric formalism
      under the first Born approximation to develop inelastic cross sections for low
      energy electron transport in liquid water. A Drude model was used to describe the
      energy-loss distribution at the dipole limit on the basis of optical data, while
      the impulse approximation and an empirical generalised-oscillator-strength
      provided the extension to finite momentum transfer. Born corrections established
      earlier for water vapour were applied at low impact energies. Core-electron
      transitions were treated by a binary model with exchange terms. Sum-rules were
      satisfied to within 1-2% while an 1-value of about 80 eV was obtained. A
      comparison with other studies is provided.

PMID- 12194337
TI  - Microdosimetric distribution of protons, Ep = 19-65 MeV, measured with a low
      pressure proportional counter.
AB  - Microdosimetric measurements of 19, 32, 43, 55, and 65 MeV protons were carried
      out with the A-150-walled low pressure proportional counter (LPPC). The spectra
      are deconvoluted into three components, which are energy loss by directly
      incident protons, secondary electrons, and scattered protons and heavy charged
      particle (including protons) produced by proton nuclear reactions with the TE
      wall. Dose-mean lineal energies of protons are large as usual, because larger
      lineal energies by proton reaction events are affected.

PMID- 12194338
TI  - Microdosimetric characterisation of 28 kVp Mo/Mo, Rh/Rh, Rh/Al, W/Rh and Mo/Rh
      mammography X ray spectra.
AB  - Microdosimetric characteristics of 28 kVp mammography X ray spectra were studied
      for several target/added filtration combinations (Mo/Mo, Rh/Rh, Rh/Al, W/Rh,
      Mo/Rh). Monte Carlo techniques were used to model X ray production from
      mammography units and to calculate distributions of absorbed dose and energy
      imparted in breast tissue. The results show that the dose averaged lineal energy
      is about 5.0 keV.micron-1, about 25% higher than for general diagnostic imaging X
      ray spectra. Significant differences in lineal energy between the five X ray
      qualities were noted, with the highest value for the commonly used Mo/Mo
      combination. Spectral hardening with depth in the tissues causes a 5% decrease in
      lineal energy over 5 cm. No significant differences were found for the different
      tissue compositions.

PMID- 12194339
TI  - 3D dosimetry study of 188Re liquid balloon for intravascular brachytherapy using
      bang polymer gel dosemeters.
AB  - It has been suggested that the combination of intravascular brachytherapy and
      coronary stent implantation may result in further reduction of restenosis after
      percutaneous balloon angioplasty. The use of an angioplasty balloon filled with a
      188Re liquid beta source for intravascular brachytherapy provides the advantages
      of accurate source positioning and uniform dose distribution to the coronary
      vessel wall. The effect of source edge and stent on the dose distribution of the
      target tissue may be clinically important. In BANG gels, the absorbed radiation
      produces free-radical chain polymerisation of acrylic monomers that are initially
      dissolved in the gel. The number of polymer particles is proportional to the
      absorbed dose. In this study, 3D dose distributions are presented for 188Re
      balloons, with and without stents, using a prototype He-Ne laser CT scanner and
      the proprietary BANG polymer gel dosemeters.

PMID- 12194340
TI  - On the equivalence of propane-based tissue-equivalent gas and liquid water with
      respect to the ionisation-yield formation by electrons and alpha-particles.
AB  - One encouraging way, at present, to put the investigation of ionisation-yield
      formation in sub-cellular structures or, at least, in nanometric volumes of
      liquid water on an experimental basis is the use of highly sophisticated counters
      filled with gases at low operating pressure to simulate target volumes a few nm
      in diameter at unit density. To check the validity of such measurements, the
      ionisation-yield formation by electrons and alpha particles in liquid water was
      simulated using the Monte Carlo method and compared with that produced in propane
      based tissue-equivalent gas (composition by volume: 55% C3H8, 39.6% CO2, 5.4%
      N2). After a short summary of the most important physical aspects of ionisation
      cluster formation, new results are presented and discussed from the point of view
      of radiation physics and radiation biology.

PMID- 12194341
TI  - Significance of fractionated irradiation for the biological therapeutic gain of
      carbon ions.
AB  - It is well established that the RBE (relative biological effectiveness) for cell
      killing depends on LET (linear energy transfer), and that a maximum RBE is
      observed at approximately 150 keV.micron-1. However, the therapeutic gain depends
      on the ratio of the RBEs for the effects on the cancer cell population and the
      effects on normal tissues. The RBE of a given radiation quality depends not only
      on LET but also on dose, biological system and effect, and irradiation
      conditions. There is no data available to answer the question: which LET is
      suitable to improve the biological therapeutic gain of carbon ions? Here, three
      different LET values of 290 MeV/u carbon ions were selected, and the relative
      biological effectiveness was compared between tumour-growth retardation and skin
      damage using a murine transplantable tumour. Larger RBE values for tumours after
      than the skin type were obtained when carbon ions of intermediate LET were
      delivered daily for 2 to 5 fractions. The biological therapeutic gain would be
      high for the carbon ion SOBP if the number of fractions were correctly selected
      in clinical trials.

PMID- 12194342
TI  - Boron microquantification in oral muscosa and skin following administration of a
      neutron capture therapy agent.
AB  - Clinical trials of boron neutron capture therapy (BNCT) for intracranial tumours
      using boronophenylalanine-fructose undertaken at Harvard-MIT and Brookhaven
      National Laboratory have observed acute normal tissue reactions in the skin and
      oral mucosa. Because the range of the 10B(n, alpha)7Li reaction products is very
      short, 10-14 microns combined, knowledge of the 10B microdistribution in tissue
      is critical for understanding the microdosimetry and radiobiology of BNCT. This
      paper reports measurements of the microdistribution of 10B in an animal model,
      rat skin and tongue, using high resolution quantitative autoradiography (HRQAR),
      a neutron-induced etched track autoradiographic technique. The steep spatial
      gradient and high absolute value relative to blood of the 10B concentration
      observed in some strata of the rat tongue epithelium and skin are important for
      properly evaluating the radiobiology and the biological effectiveness factors for
      normal tissue reactions such as oral mucositis, which are generally assessed
      using the blood boron concentration rather than the tissue boron concentration.

PMID- 12194343
TI  - Heavy ion RBE and microdosimetric spectra.
AB  - Reliable values for the relative biological effectiveness (RBE) of the complex
      field of heavy ions is essential for radiation therapy with carbon beams.
      Clinical experience with this novel form of therapy is still quite narrow and it
      is, therefore, desirable to compare and combine relevant clinical findings and
      theoretical approaches. One major source of available information comes from
      neutron therapy. The approach towards the determination of RBE for neutron
      therapy is, therefore, tentatively applied to the heavy ion therapy. This
      includes the determination of microdosimetric spectra and their numerical
      evaluation towards the determination of RBE. A microdosimetric detector on the
      basis of a tissue-equivalent proportional counter (TEPC) was developed for
      measurements in the heavy ion fields of the GSI, Darmstadt. Measurements were
      performed first near the perspex phantom surface with carbon ion energies between
      89 MeV.amu-1 and 430 MeV.amu-1. Subsequently, measurements were taken at various
      depths in the neighbourhood of the Bragg region. The numerical techniques that
      were developed for neutron therapy lead to tentative values of the RBE that are
      compared to the RBE values from the biophysical model developed at the GSI. The
      comparison is still preliminary but can be helpful in modifying the
      microdosimetric approach for its application in heavy ion therapy.

PMID- 12194344
TI  - A semi-microscopic model for the evaluation of radiation damage.
AB  - A model for the biological effects of the energy deposited by ion beams on
      irradiated tissues is presented. The relevant parameters are the fractions of
      undamaged cells (where of course the definition of damaged cell depends on the
      biological end point under consideration, e.g. surviving cells) after the
      sensitive target of the cells has been traversed by any given number of ionising
      particles. The experimental parameters of the dose response curves offer a way to
      determine those of the model. The model can be formulated both for the simpler
      case of cells traversed by only one radiation quality, i.e. by a monoenergetic
      beam of a given ion, and for the general case of irradiation by a mixed field. A
      possible application in experimental data analysis is presented.

PMID- 12194345
TI  - Characterisation of an ultra-miniature counter for microdosimetric measurements
      in a therapeutic 400 MeV/A carbon beam.
AB  - Single event spectra of a clinical carbon beam have been measured by an ultra
      miniature tissue-equivalent proportional counter (UMC). In order to cover the
      energy range of the Bragg peak, the incident energy of the carbon beam was
      degraded by aluminium plates. Single event spectra for carbon-events incident to
      the UMC were analysed and selected at several carbon energies using thin
      scintillation counters. It was found that the dose weighted lineal energy
      distributions have a doublet peak structure due to incident carbon beam and
      fragment contributions.

PMID- 12194346
TI  - An investigation of energy spectrum and lineal energy variations in mega-voltage
      photon beams used for radiotherapy.
AB  - Megavoltage photon beams are routinely used for external-beam radiotherapy.
      Recently, new treatment modalities based on dynamic and intensity modulated (IM),
      beam delivery systems are increasingly used in clinical practice. The purpose of
      this work is to investigate the energy spectrum and microdosimetric features of
      these photon beams. A Monte Carlo technique was first used to simulate beam lines
      of medical accelerators and to compute photon fluence and spectrum per unit dose
      to-water inside the irradiated medium. Subsequently, a track structure code was
      used to compute the lineal energy and its distribution in a 1 micron sphere based
      on the individual photon spectrum. Results showed that the low energy photon
      component varied significantly with field size and location within the field due
      to the presence of the scattered photons. The calculated dose-mean lineal energy
      <yD> ranged from 2.3 keV.micron-1 at a depth of 1.5 cm along the central axis of
      a 4 cm x 4 cm field, to 3.7 keV.micron-1 at a depth of 20 cm of the field edge in
      a 10 cm x 10 cm field. In the tested IM fields at a depth of 10 cm, <yD> ranged
      from 2.6 to 3.5 keV.micron-1, which was inversely related to the dose intensity
      in the field. The <yD> values for the clinical photon beams were also
      significantly greater than that of a reference 60Co beam (1.8 keV.micron-1 from
      the calculation). The beam quality factor was estimated to vary within 20% due to
      the change of the energy spectrum for the radiotherapy photon fields.

PMID- 12194347
TI  - A theoretical model for the microdosimetry of discontinuous distributions of
      heavy particle tracks.
AB  - A novel approach to solving microdosimetry problems using conditional
      probabilities and geometric concepts has been developed. This approach is valid
      for cases where a convex site is immersed in uniform or discontinuous
      distributions of heavy charged particle tracks and assumes no restrictions in
      site geometry or the kind of randomness. These conditions are relevant to the
      study of microdosimetry in applications such as neutron capture therapy (NCT),
      irradiation experiments using heavy ion particle beams, environmental radon, or
      occupational exposure to radioactive materials. Expressions applicable to the
      case of surface-distributed sources of tracks are presented that may represent
      situations such as NCT, where boron compounds are bound to the membranes of
      cellular nuclei. Microdosimetric spectra, specific energy averages, and mean
      number of 10B capture reactions for cell inactivation are calculated, showing
      their dependence on 10B localisation.

PMID- 12194348
TI  - Microdosimetric characteristics of the clinical proton beams at JINR, Dubna.
AB  - High-energy proton radiotherapy beams give rise to secondary heavy charged
      particles with elevated linear energy transfer (LET), which contribute to the
      dose in a patient. This contribution to the characteristics of radiotherapy
      proton beams was experimentally studied by means of a LET spectrometer based on a
      track detector. The spectrometer permits LET spectra to be established in the
      region above 10 keV.micron-1 in tissue. Sets of track detectors were exposed in
      the various depths of a phantom irradiated with protons of two energies, 150 and
      205 MeV. It was observed that the contribution of particles with the values of
      LET mentioned increases with the depth, representing from about 2 (at the
      surface) up to few tens% close to Bragg peak region of the total dose. There,
      some of primary protons contribute also above 10 keV.micron-1. Using the
      'biological weighted function' proposed, the clinical RBE was calculated, it
      could approach 1.3. This effect has to be taken into account during the clinical
      beam production and the radiotherapy.

PMID- 12194349
TI  - The evaluation and use of a portable TEPC system for measuring in-flight exposure
      to cosmic radiation.
AB  - A recent EC directive has called for all member states to introduce legislation
      covering the assessment and restriction of air crew exposure to cosmic radiation.
      In the UK the Civil Aviation Authority, in conjunction with the Department of the
      Environment. Transport and the Regions issued guidelines suggesting the use of a
      predictive code such as CARI for this purpose. In order to validate the use of
      calculated route doses, an extensive programme of measurements is being carried
      out on long haul routes in conjunction with Virgin Atlantic Airways, using a
      prototype HAWK TEPC developed by Far West Technology. This programme began in
      January 2000 and by the end of February 2001 had resulted in the accumulation of
      data from 74 flights. In this paper the instrument design is discussed, together
      with the calibration programme. An overview of the in-flight results is also
      presented, including comparisons between measurements and calculations, which
      indicates that CARI under-predicts the route doses by approximately 20%.

PMID- 12194350
TI  - On a model-based approach to radiation protection.
AB  - There is a preoccupation with linearity and absorbed dose as the basic
      quantifiers of radiation hazard. An alternative is the fluence approach, whereby
      radiation hazard may be evaluated, at least in principle, via an appropriate
      action cross section. In order to compare these approaches, it may be useful to
      discuss them as quantitative descriptors of survival and transformation-like
      endpoints in cell cultures in vitro--a system thought to be relevant to modelling
      radiation hazard. If absorbed dose is used to quantify these biological
      endpoints, then non-linear dose-effect relations have to be described, and, e.g.
      after doses of densely ionising radiation, dose-correction factors as high as 20
      are required. In the fluence approach only exponential effect-fluence
      relationships can be readily described. Neither approach alone exhausts the scope
      of experimentally observed dependences of effect on dose or fluence. Two
      component models, incorporating a suitable mixture of the two approaches, are
      required. An example of such a model is the cellular track structure theory
      developed by Katz over thirty years ago. The practical consequences of modelling
      radiation hazard using this mixed two-component approach are discussed.

PMID- 12194351
TI  - Biological weighting of absorbed dose in radiation therapy.
AB  - Absorbed dose is a quantity which is scientifically rigorously defined and used
      to quantify the exposure of biological objects, including humans, to ionising
      radiation. There is, however, no unique relationship between absorbed dose and
      induced biological effects. The effects induced by a given absorbed dose to a
      given biological object depend also on radiation quality and temporal
      distribution of the irradiation. In radiation therapy, empirical approaches are
      still used today to account for these dependencies in practice. In hadron therapy
      (neutrons, protons, ions), radiation quality is accounted for with a diversity of
      (almost hospital specific) methods. The necessity to account for temporal aspects
      is well known in external beam therapy and in high dose rate brachytherapy. The
      paper reviews the approaches for weighting the absorbed dose in radiation
      therapy, and focusses on the clinical aspects of these approaches, in particular
      the accuracy requirements.

PMID- 12194352
TI  - Energy deposition, cellular radiation effects and lung cancer risk by radon
      progeny alpha particles.
AB  - Slowing down spectra, LET spectra, hit probabilities, and radiation doses were
      simulated for the interaction of single 218Po and 214Po alpha particles with
      sensitive basal and secretory cell nuclei in the bronchial epithelium of human
      and rat lungs for defined exposure conditions. Probabilities per unit track
      length for transformation, derived from in vitro experiments with C3H 10T1/2
      cells, were used to estimate transformation probabilities for randon progeny
      alpha particles in basal and secretory cells. Different weighting schemes were
      assumed to relate cellular hit probabilities, doses and transformation
      probabilities, obtained for different cell depths and airway generations, to lung
      cancer risk per unit exposure. In vitro transformation and in vivo lung cancer
      incidence were simulated by a state-vector model which provides a stochastic
      formulation of dose-rate dependent cellular transitions related to formation of
      double strand breaks, repair, inactivation, stimulated mitosis and promotion
      through loss of intercellular communication.

PMID- 12194354
TI  - Monte Carlo code for microdosimetry of inhaled alpha emitters.
AB  - A Monte Carlo code has been developed to calculate the local energy deposited by
      alpha emitters deposited on the inner surface in the lung airway. Developed to
      deal further with airway bifurcations, this code has been as a first step
      validated in a cylindrical airway configuration by comparison with well
      established analytical codes in the case of contamination of bronchiolar airways
      with actinides. The code has then been applied to the study of uniform and non
      uniform contamination of cylindrical bronchial airways by radon progeny in indoor
      and mine exposure conditions. In addition to the microdosimetric spectra, the
      average microdosimetric parameters (zp, n, z) have been evaluated. The work
      currently in progress consists in adapting this developed Monte Carlo code to the
      configuration of an airway bifurcation with realistic particles deposition.

PMID- 12194353
TI  - Assessing the uniformity of plutonium alpha radiation dose in human lung: the
      Mayak experience.
AB  - Radiation-induced lung cancer risk is currently estimated based on
      epidemiological data from populations exposed either to relatively uniform, low
      LET radiation, or from uranium miners who inhaled radon and its progeny. Inhaled
      alpha-emitting radionuclides (e.g. Pu and Am) produce distinctive dose patterns
      that may not be adequately modelled at present. Thus the distribution of Pu is
      being measured in formalin-fixed autopsy lung tissue from former workers at the
      Mayak Production Association, and which is maintained in a tissue archive at
      SUBI. Lungs are sampled using contemporary stereological techniques and Pu
      particle activities and locations are determined using quantitative
      autoradiography and morphological identification of lung structures. To date, >
      80% of Pu particles have been observed in parenchymal lung tissues with higher
      concentrations being found in scar tissue. Concentrations of Pu particles in
      conducting airways are uniformly low, thus indicating that long-term-retained Pu
      particles are non-uniformly distributed in human lung, mostly in the parenchyma.

PMID- 12194355
TI  - Local deposition distributions of inhaled radionuclides in the human
      tracheobronchial tree.
AB  - There is experimental evidence that bronchogenic carcinomas originate mainly at
      the carinal ridges of the large central airways, where primary hot spots of
      deposition have been found. However, current lung dosimetry models do not take
      into consideration the inhomogeneity of deposition within the airways. In this
      study, computed local distributions of deposited inhaled radionuclides such as
      radon progenies in morphologically realistic human airway bifurcation models are
      analysed for different flow rates and particle sizes. Then, local deposition
      enhancement factors, defined as the ratio of local to average deposition
      densities, are computed by scanning along the surface of the bifurcation with pre
      specified surface area elements. Computed enhancement factors indicate that cells
      located at carinal ridges or at the inner sides of the progeny branches may
      receive localised doses which are two orders of magnitude higher than the average
      values.

PMID- 12194356
TI  - Simulation code for the interaction of 14 MeV neutrons on cells.
AB  - The structure of the survival curve of melanoma cells irradiated by 14 MeV
      neutrons displays unusual features at very low dose rate where a marked increase
      in cell killings at 0.05 Gy is followed by a plateau for survival from 0.1 to
      0.32 Gy. In parallel a simulation code was constructed for the interaction of 14
      MeV neutrons with cellular cultures. The code describes the interaction of the
      neutrons with the atomic nuclei of the cellular medium and of the external medium
      (flask culture and culture medium), and is used to compute the deposited energy
      into the cell volume. It was found that the large energy transfer events
      associated with heavy charged recoils can occur and that a large part of the
      energy deposition events are due to recoil protons emitted from the external
      medium. It is suggested that such events could partially explain the experimental
      results.

PMID- 12194357
TI  - Microbeams, microdosimetry and specific dose.
AB  - Dose and its usefulness as a single parameter to describe the amount of radiation
      absorbed are well established for most situations. The conditions where the
      concept of dose starts to break down are well known, mostly from the study of
      microdosimetry. For low doses of high LET radiation it is noted that the process
      of taking the limiting value of the energy absorbed within a test volume divided
      by the mass within that volume yields either zero or a relatively large value.
      The problem is further exacerbated with microbeam irradiations where the
      uniformity of the energy deposition is experimentally manipulated on the spatial
      scale of cells being irradiated. Booz introduced a quantity to deal with these
      problems: the unfortunately named 'mean specific energy in affected volumes'.
      This quantity multiplied by the probability that a test volume has received an
      energy deposit is equal to dose (in situations where dose can be defined). I
      propose that Booz's quantity be renamed 'specific dose', that is the mean energy
      deposited divided by the mass within a specified volume. If we believe for
      instance that the nucleus of a cell is the critical volume for biological
      effects, we can refer to the nuclear specific dose. A microbeam experiment
      wherein 10 per cent of the cell nuclei were targeted with 10 alpha particles
      would be described as delivering a nuclear specific dose of 1.6 Gy to 10 per cent
      of the population.

PMID- 12194358
TI  - Self-absorption effects on electron absorbed fraction in the anterior nose.
AB  - The electron absorbed fraction in the anterior nose is estimated in the
      International Commission on Radiological Protection Publication 66 using the EGS4
      Code and a cylinder model. The electrons are assumed to come from point sources
      lining the inner surface of the nose. Although the radioactive source particles
      are carried in dust, self-absorption in the dust is ignored. Consequently, the
      absorbed fractions published in ICRP 66 cannot represent the correct energy
      deposition in the basal cell region. In this work we estimate the energy lost by
      the emitted electrons inside spherical dust particles, which vary in diameter
      from 1 micron to 100 microns. The absorbed fractions in the basal cell layer are
      then estimated using the modified electron energy spectrum. To illustrate these
      effects, modified absorbed fractions for a dust particle radius of 20 microns are
      compared to the absorbed fractions presented in ICRP 66. Significant differences
      are noted.

PMID- 12194359
TI  - Modelling interaction cross sections for intermediate and low energy ions.
AB  - When charged particles slow in tissue they undergo electron capture and loss
      processes that can have profound effects on subsequent interaction cross
      sections. Although a large amount of data exists for the interaction of bare
      charged particles with atoms and molecules, few experiments have been reported
      for these 'dressed' particles. Projectile electrons contribute to an impact
      parameter-dependent screening of the projectile charge that precludes
      straightforward scaling of energy loss cross sections from those of bare charged
      particles. The objective of this work is to develop an analytical model for the
      energy-loss-dependent effects of screening on differential ionisation cross
      sections that can be used in track structure calculations for high LET ions. As a
      first step a model of differential ionisation cross sections for bare ions has
      been combined with a simple screening model to explore cross sections for
      intermediate and low energy dressed ions in collisions with atomic and molecular
      gas targets. The model is described briefly and preliminary results compared to
      measured ejected electron energy spectra.

PMID- 12194360
TI  - Track structure for low energy ions including charge exchange processes.
AB  - The model and development is described of a new generation of Monte Carlo track
      structure codes. The code LEPHIST simulates full slowing down of low-energy
      proton history tracks in the range 1 keV-1 MeV and the code LEAHIST simulates low
      energy alpha particle history tracks in the range 1 keV-8 MeV in water. All
      primary ion interactions are followed down to 1 keV and all electrons to 1 eV.
      Tracks of secondary electrons ejected by ions were traced using the electron code
      KURBUC. Microdosimetric parameters derived by analysis of generated tracks are
      presented.

PMID- 12194361
TI  - Mechanisms of low energy electron damage to condensed biomolecules and DNA.
AB  - It has recently been shown that 3-20 eV electron impact on vacuum-dry samples of
      plasmid DNA induced substantial yields of single and double strand breaks (SSBs
      and DSBs). These results are summarised in the present article along with those
      obtained from the fragmentation of elementary components (i.e. condensed H2O,
      bases and sugar analogues) of DNA induced by low energy electron impact under
      ultra high vacuum conditions. By comparing the results from these experiments, it
      is possible to determine fundamental mechanisms by which low energy electrons
      damage DNA. The decay of transient anions formed on the DNA's basic components is
      found to play a crucial role in producing SSBs and DSBs. Since a large portion of
      the energy deposited by ionising radiation first leads to the production of low
      energy secondary electrons, these findings provide basic knowledge necessary to
      understand the genotoxic effects of high energy radiation and eventually modify
      these effects at the molecular level.

PMID- 12194362
TI  - Chemical aspects of clustered DNA damage induction by ionising radiation.
AB  - Ionising radiation induces a variety of chemical modifications to DNA, ranging
      from simple, isolated lesions to clustered DNA damage, in which two or more
      lesions are formed within a few tens of base pairs by a single radiation track.
      Multiple lesions, e.g. tandem lesions and amplification of damage, may also be
      induced in DNA by reaction with a single hydroxyl radical. It has been proposed
      from biophysical modelling that clustered DNA damage is less repairable and
      therefore contributes to the biological severity of ionising radiation. In this
      review, some evidence is presented which indicates that non-double strand break
      (non-DSB) clustered DNA damage is induced in significant yield, relative to that
      of DSBs, in mammalian cells. Enzymatic processing of clustered DNA damage in
      synthetic oligonucleotides has been shown to be compromised, depending on the
      nature of the lesions present. The role of clustered DNA damage in the early
      stages of the development of radiation-induced carcinogenesis remains to be
      addressed.

PMID- 12194363
TI  - Computer simulation of 57Fe bleomycin auger effects in DNA.
AB  - The antibiotic bleomycin binds to the DNA and induces double strand breaks
      (DSBs). To increase the cleavages. 57Fe is used to form a complex suitable for
      Mossbauer effect. The de-excitation of the resonant excited 57Fe nucleus releases
      Auger electrons and X rays. The goal of this work is to evaluate the increase in
      yield of DSBs due to the 57Fe, using Monte Carlo simulation methods. Particles
      spectra and the yields of single strand breaks (SSBs) and DSBs were calculated by
      considering direct events on DNA and reaction of all radical species generated in
      the radiolysis of its environment. The Auger spectrum shows a large number of
      electrons with energies below 100 eV, mainly responsible for direct damage, while
      another group around 600-700 eV is responsible for indirect damage effects.
      Bleomycin receives about one fourth of the energy deposited in DNA and an average
      of 0.65 DSB per de-excitation is observed.

PMID- 12194364
TI  - Stochastic simulation of gamma radiolysis of acidic ferrous sulfate solution at
      elevated temperatures.
AB  - The effect of temperature on the oxidation of Fe2+ in the gamma radiolysis of
      acidic ferrous sulfate solutions has been modelled using the stochastic IRT
      method, incorporating simulated electron track structures. There is an 11%
      increase in the Fe3+ yield in aerated 0.4 M H2SO4 solution on going from 298 to
      573 K (25 to 300 degrees C). The H2 yield in aerated solution increases about 24%
      from 0.41 at 298 K to 0.51 at 573 K. In the absence of oxygen, the increase in
      the yields of both Fe3+ and H2 is about 12%. Calculated yields are consistent
      with available experimental data at room, and elevated temperatures. Simulations
      for heavy water (D2O) show similar temperature effects to those found for ferrous
      sulfate solutions in light water (H2O).

PMID- 12194365
TI  - Modelling of DNA damage induced by energetic electrons (100 eV to 100 keV).
AB  - Modelling and calculations are presented for the spectrum of initial DNA damage
      produced by 100 eV to 100 keV energetic electrons. Analysis of the initial
      spectrum of damage, based upon the source (direct energy deposition and reactions
      with diffusing OH radicals) and complexity of damage, indicates that the majority
      of the interactions cause no damage to DNA and any damage that does occur is most
      likely to be a simple single strand break (SSB). The fraction of complex damage
      for energetic electrons is lower than that induced by low energy electrons and
      ultrasoft X rays but still represents an appreciable fraction (20-30%) of the
      total double strand breaks (DSBs). Relative yields of strand breaks are
      investigated for dependence on the assumed energy deposition threshold and on the
      probability of the hydroxyl radicals to produce a single strand break. The ratio
      of direct to indirect damage does not change significantly across the electron
      energy range investigated and the values lie well within the experimental data.
      The direct energy deposition in DNA represents a larger proportion of the damage
      although the contribution from the hydroxyl radicals is also substantial, both in
      terms of the absolute yield of the breaks and the complexity of the damage.

PMID- 12194366
TI  - Ratio of complex double strand break damage induced by 125IUdR and 123IUdR
      correlates with experimental in vitro cell killing effectiveness.
AB  - The overall cellular damage induced by ionising radiation is determined by the
      number and spatial distribution of initial ionisations and excitations within the
      critical volume. This paper focuses on the physical and chemical phase of the
      radiation action chain following the decay of DNA-bound 123I and 125I. Monte
      Carlo simulations of these nuclides' decay provide electron emission spectra
      which are used as input data for track structure calculations. In combination
      with DNA models, these calculations allow the specific radiation source to be
      characterised in terms of DNA strand break patterns. The distribution of these
      patterns indicates that 125I produces much more severe breaks than 123I. The
      ratio of complex DSBs induced by both iodine isotopes correlates with the
      differences in cell killing effectiveness reported from in vitro survival
      experiments.

PMID- 12194368
TI  - Computational model of the modulation of gene expression following DNA damage.
AB  - High linear energy transfer (LET) radiation, such as heavy ions or neutrons, has
      an increased biological effectiveness compared to X rays for gene mutation,
      genomic instability, and carcinogenesis. In the traditional paradigm, mutations
      or chromosomal aberrations are causative of late effects. However, in recent
      years experimental evidence has demonstrated the important role of the
      description of the modification of gene expression by radiation in understanding
      the mechanisms of radiation action. In this report, approaches are discussed to
      the mathematical description of mRNA and protein expression kinetics following
      DNA damage. Several hypotheses for models of radiation modulation of protein
      expression are discussed including possible non-linear processes that evolve from
      the linear dose responses that follow the initial DNA damage produced by
      radiation.

PMID- 12194369
TI  - Quantitative analysis of the energetics of DNA damage.
AB  - Application of Monte Carlo track structure has been very successful in the
      modelling and quantification of DNA damage, clustered-damage and spectrum of DNA
      damage for energetic electrons and ions. However, there are paradoxical axioms in
      quantitative assessment of the energetics of DNA damage at very low electron
      energy and in the vacuum UV region. This paper, after a brief review of the
      parameters used in modelling of DNA damage, presents an analysis of experimental
      data of strand breaks in aqueous solution in the vacuum UV, the region to which
      little attention has been paid in spite of its fundamental importance in
      providing reaction parameters for radiation actions.

PMID- 12194367
TI  - Biological effects induced by K photo-ionisation in and near constituent atoms of
      DNA.
AB  - In order to assess the lethal efficiency and other biological effects of inner
      shell ionisations of constituent atoms of DNA ('K' events), experiments were
      developed at the LURE synchrotron facility using ultrasoft X rays as a probe of K
      events. The lethal efficiency of ultrasoft X rays above the carbon K threshold
      was especially investigated using V79 cells and compared with their efficiency to
      induce double strand breaks in dry plasmid-DNA. A correlation between the K event
      efficiencies for these processes is shown. Beams at 340 eV were found to be twice
      as efficient at killing cells than were beams at 250 eV. In addition, a rough two
      fold increase of the relative biological effectiveness for dicentric + ring
      induction has also been observed between 250 and 340 eV radiations.

PMID- 12194370
TI  - Simulation of DNA damage after proton and low LET irradiation.
AB  - A module for proton track structure simulation in liquid water was implemented in
      the biophysical model PARTRAC. Simulated tracks of energy deposition events from
      the radiation under investigation were superimposed on a higher-order DNA target
      model describing the whole genome inside a human cell. The parameters controlling
      DNA damage from direct and indirect effects were adapted to agree with yields and
      pathway contributions derived from gamma ray irradiation experiments. Single and
      double strand break (DSB) induction was simulated for irradiations by protons,
      photons and electrons over a wide range of initial energies. The relative
      biological effectiveness for DSB induction after proton irradiation was found to
      rise from 1.2 at 5 keV.micron-1 to about 2.5 at 70 keV.micron-1. About half of
      this growth resulted from an increased production of DSB clusters associated with
      small (< 10 kbp) fragments.

PMID- 12194371
TI  - [Summing up an experience].

PMID- 12194372
TI  - [Beyond the history of cardiac surgery in Portugal].

PMID- 12194373
TI  - Tissue Doppler imaging and long axis left ventricular function: hypertrophic
      cardiomyopathy versus athlete's heart.
AB  - BACKGROUND: The different diagnosis between hypertrophic cardiomyopathy and
      athlete's heart has important clinical implications. The assessment of long axis
      left ventricular function with tissue Doppler imaging in hypertrophic
      cardiomyopathy (showing systolic and diastolic dysfunction with heterogeneity and
      asynchrony), may be useful in the differentiation of these situations. AIM: To
      study, with tissue Doppler imaging, long axis left ventricular function in a
      population of athletes (rowers) and to compare it with a population of non
      obstructive hypertrophic cardiomyopathy patients. METHODS: In 24 patients with
      non-obstructive hypertrophic cardiomyopathy and in 20 competitive rowers with
      similar age, blood pressure and heart rate, we analyzed mitral annulus motion
      with pulsed tissue Doppler imaging in the 4 sides of the annulus (septal,
      lateral, inferior, anterior), in apical views. In each wave (systolic, rapid
      filling and atrial contraction) we measured velocities, time intervals and
      velocity-time integrals, and calculated heterogeneity and asynchrony indices.
      Data were compared between the groups, between the different sides in each group
      ("parallel analysis") and with conventional indices of global function. RESULTS:
      Hypertrophic cardiomyopathy patients showed: systolic function: lower velocities
      and integrals, shorter ejection time and shorter systolic time. These
      abnormalities occurred even in annular sites contiguous to walls without
      hypertrophy. DIASTOLIC FUNCTION: Much lower rapid filling velocities and
      integrals, lower atrial contraction velocities and integrals, lower e/a, longer
      isovolumic relaxation time and time to peak rapid filling wave. These
      abnormalities occurred even in annular sites adjacent to walls without
      hypertrophy. In the athletes group, the e/a ratio was never < 1, in any annular
      site. In hypertrophic cardiomyopathy patients this ratio was < 1 in 27% of the
      sites. CONCLUSIONS: 1--Systolic and diastolic long axis left ventricular function
      is different in hypertrophic cardiomyopathy and in athletes, in all mitral
      annulus sides. 2--The presence of these abnormalities in annular sites contiguous
      to walls without hypertrophy suggests that this technique may be useful in the
      differential diagnosis between these groups, particularly in the "gray zone" of
      Maron.

PMID- 12194374
TI  - Tissue Doppler imaging assessment of long axis left ventricular function in
      hypertensive patients with concentric left ventricular hypertrophy: differential
      diagnosis with hypertrophic cardiomyopathy.
AB  - BACKGROUND: The differential diagnosis between hypertrophic cardiomyopathy and
      hypertensive heart disease has clinical, therapeutic and prognostic implications,
      but is not always easy with conventional echocardiography. Tissue Doppler imaging
      of the mitral annulus allows the detailed study of long axis left ventricular
      function in hypertrophic cardiomyopathy and may be useful in the differential
      diagnosis. METHODS: 23 patients with non-obstructive hypertrophic cardiomyopathy
      and 25 hypertensive patients with concentric left ventricular hypertrophy with
      similar age, body surface and heart rate were studied with pulsed tissue Doppler
      imaging of the 4 sides of the mitral annulus (septal, lateral, inferior,
      anterior) in 4 and 2 chamber views. In each wave (systolic-s, rapid filling-e,
      atrial contraction-a) we analyzed velocities, time intervals and velocity-time
      integrals, as well as heterogeneity and asynchrony. Data were compared among the
      different sides in each group, between groups and with conventional Doppler data.
      RESULTS: In contrast to hypertensive patients, hypertrophic cardiomyopathy
      patients showed: 1--Systolic function: lower "s" wave velocities and integrals,
      higher systolic heterogeneity, longer isovolumic relaxation time and higher
      PEP/LVET (pre ejection period/left ventricular ejection time). 2--Diastolic
      function: lower "e" and "a" wave, higher "a" and "e/a" heterogeneity index,
      higher percentage of annular sides with e/a > or = l, longer isovolumic
      relaxation time and time to peak e, and higher diastolic asynchrony. Some of
      these abnormalities occurred in annular sides adjacent to non-hypertrophied
      walls. CONCLUSIONS: This study shows that: 1--Long axis systolic and diastolic
      left ventricular function are significantly different between hypertrophic
      cardiomyopathy patients and hypertensive patients with concentric left
      ventricular hypertrophy. 2--These functional differences occur in the velocity
      domain (with heterogeneity), in the time domain (with asynchrony) and also in
      velocity time integrals. 3--Long axis systolic and diastolic dysfunction occur in
      annular sides contiguous to hypertrophied and non-hypertrophied walls, enhancing
      the role of tissue Doppler imaging in the differential diagnosis between these
      diseases.

PMID- 12194375
TI  - Doppler tissue techniques: when will they become routine in laboratories?

PMID- 12194376
TI  - Simultaneous catheterization of the coronary arteries in the treatment of chronic
      total occlusions.
AB  - Chronic total occlusions present technical challenges to the interventional
      cardiologist, and are accompanied by an increased propensity for complications.
      We present an argument for the routine use of simultaneous bilateral coronary
      angiography to help define the lesion and optimize the therapeutic approach.
      Eight selected cases of CTO were revascularized using this technique resulting in
      immediate procedural success, devoid of complications, in all cases.

PMID- 12194378
TI  - Coronary surgery in patients with porcelain aorta.
AB  - Four patients with unstable angina due to left main or three-vessel disease
      scheduled for coronary artery bypass grafting were found intra-operatively to
      have porcelain ascending aorta, defined as massive calcification of the ascending
      aorta from the aortic valve to the transverse arch, precluding ascending aorta
      cannulation or clamping. A no-touch operative technique was applied using the two
      internal mammary arteries in three cases, with complementary Y-grafting when
      necessary. Three cases underwent off-pump myocardial revascularization. The
      fourth case was revascularized with pump-assisted beating heart and proximal
      saphenous graft anastomosis with an automatic connector. There was no mortality
      or neurologic morbidity and all patients were discharged home before post
      operative day 8.

PMID- 12194377
TI  - Impact of diabetes on induction of the mitochondrial permeability transition.
AB  - Diabetes is one of the most common metabolic diseases of our times. Specific
      cardiovascular alterations are often associated with the progression of this
      disease. Considerable controversy exists in the literature concerning the greater
      or lesser susceptibility of the diabetic heart to ischemia and reperfusion.
      Cardiac mitochondria may be fundamental to the differential susceptibility of the
      cardiomyocyte to pathologic phenomena, particularly those due to the induction of
      the degenerative process known as the mitochondrial permeability transition
      (MPT), which is triggered by excessive mitochondrial calcium accumulation. The
      MPT has been associated with cellular dysfunction resulting from ischemia and
      reperfusion. The objective of this work was to examine the susceptibility of
      mitochondria isolated from diabetic rats to the MPT, in comparison to healthy
      control rats of the same age. Cardiac mitochondria from the diabetic rats had
      higher calcium loading capacity before the development of the MPT, with a
      decreased incidence of MPTP-associated features. This was associated with a
      greater capacity to sustain multiple pulses of externally added calcium,
      simultaneously with maintenance of the transmembrane electrical potential and
      reduced swelling amplitude. This could mean that cardiomyocytes from diabetic
      hearts may indeed be less prone to dysfunctions resulting from ischemia and
      reperfusion, at least in milder diabetic conditions, thus explaining many reports
      in the literature.

PMID- 12194379
TI  - Basics of methodologic analysis of therapeutic trials. Part III: applicability of
      the results to the individual patient.
AB  - One of the most compelling questions a cardiologist (and, for that matter, any
      clinician) has to face involves choosing the optimal management strategy for
      their patients. One of the best sources of information about therapy is the
      randomized controlled trial, which, despite several significant shortcomings, is
      considered to be the gold standard in studies about therapeutics and prevention.
      The methodologic quality of therapeutic trials is highly variable and--as already
      discussed in previous articles--in order to be useful they have to be critically
      appraised in terms of the validity of their results, their importance, and their
      applicability to the individual patient. In two previous articles published in
      the Journal, critical appraisal of evidence in therapeutic trials was presented,
      concerning the validity and the importance of the results. In this article, we
      will present a critical appraisal of the applicability of the results to the
      individual patient.

PMID- 12194380
TI  - Pseudo-aneurysm of the aortic root in a patient with mechanical aortic
      prosthesis.
AB  - The authors describe a case of an ex-intravenous drug user, who received
      mechanical valve prostheses in the aortic and mitral position for Staphylococcus
      aureus endocarditis and developed a pseudo-aneurysm of the aortic root with major
      peri-valvular regurgitation one year after surgery. The images of the
      transesophageal echocardiogram are presented.

PMID- 12194381
TI  - Risks and benefits of DNA testing for neurogenetic disorders.
AB  - DNA testing for mutations in genes causing neurogenetic disorders is becoming a
      common practice in clinical neurology. The tests are highly sensitive and
      specific. They are especially valuable in establishing diagnoses in symptomatic
      patients. These DNA tests are also used in asymptomatic persons at risk for
      genetic diseases who wish to determine whether or not they have inherited an
      abnormal gene. There are risks and benefits to such asymptomatic, predictive
      testing. A number of complex issues need to be considered including precipitation
      of depression, prenatal diagnosis and testing of children, impact on insurance
      and employment, legal aspects, possible third-party coercion, and an
      understanding of each test's limitations. Therefore, these DNA tests need to be
      used with careful clinical judgment and in the context of each individual patient
      and family.

PMID- 12194382
TI  - Diagnosis and treatment of Wilson's disease.
AB  - Wilson's disease is due to an inherited defect in copper excretion into the bile
      by the liver. The resulting copper accumulation and copper toxicity results in
      liver disease, and in some patients, brain damage. Patients present, generally
      between the ages of 10 and 40 years, with liver disease, neurological disease of
      a movement disorder type, or behavioral abnormalities, and often with a
      combination of these. Because Wilson's disease is effectively treated, it is
      extremely important for physicians to learn to recognize and diagnose the
      disease. Treatment options have evolved rapidly in the last few years, with zinc
      now being the drug of choice in most situations.

PMID- 12194383
TI  - Genetics of primary dystonia.
AB  - Currently, at least 12 types of dystonia can be distinguished on a genetic basis.
      Advances in the molecular genetics of dystonia have led to the recent
      identification of a 3-bp deletion in the DYT1 gene, causing early-onset
      generalized torsion dystonia (TD), and to the detection of mutations in the GTP
      cyclohydrolase I and the tyrosine hydroxylase genes causing dopa-responsive
      dystonia (DYT5). A missense change in the D2 dopamine receptor has been shown to
      be associated with myoclonus-dystonia in one family. In addition, six other
      dystonia gene loci have been mapped to chromosomal regions, including a locus for
      a mixed dystonia phenotype (DYT6), one form of focal dystonia (DYT7), two types
      of paroxysmal dystonia (DYT8, DYT9), X-linked dystonia-parkinsonism (DYT3), and
      rapid-onset dystonia parkinsonism (DYT12). No positive linkage studies have as
      yet been reported for autosomal recessive TD (DYT2) and in several other large
      families with various types of dominantly inherited TD (DYT4). It may be
      anticipated that the traditional clinical and etiological classifications of
      dystonia will increasingly be replaced by a genetic one and that the
      identification of more dystonia genes may lead to a better understanding of these
      largely nondegenerative disorders.

PMID- 12194384
TI  - Genetic aspects of multiple sclerosis.
AB  - A large body of immunological, epidemiological, and genetic data indicate that
      tissue injury in multiple sclerosis (MS) results from an abnormal immune response
      to one or more myelin antigens that develops in genetically susceptible
      individuals after exposure to an as-yet undefined causal agent. A genetic
      component in MS is indicated by an increased relative risk to siblings compared
      to the general population, and an increased concordance rate in monozygotic
      compared to dizygotic twins. The past few years have seen real progress in
      defining the genetic basis of MS setting the stage for new approaches for the
      final characterization of the genes involved in MS susceptibility and
      pathogenesis. Whole genome screens conducted in different populations identified
      discrete chromosomal regions potentially harboring MS susceptibility genes,
      however, with the exception of the Major Histocompatibility Complex (MHC) on
      6p21, no single locus generated overwhelming evidence of linkage. These results
      suggest a complex genetic etiology, including multiple genes of small to moderate
      effect and probable genetic heterogeneity. The identification and
      characterization of MS susceptibility genes and their correlation with disease
      phenotypes is likely to define the basic etiology of the disease, improve risk
      assessment, and influence therapeutics.

PMID- 12194385
TI  - Expanded repeat sequences and disease.
AB  - The clinical phenomenon of an earlier age of onset or a more severe phenotype in
      later generations of a family has been termed anticipation. In a number of
      neurological and neuropsychiatric disorders, the anticipation has been linked to
      expanded repeat sequences that increase in size upon transmission. This novel
      mutational mechanism has been demonstrated in more than 15 disorders today. The
      repeat sequence motif (base composition), size, and localization of expanded
      repeats within the respective disease genes vary between disorders and influence
      the way the repeat causes disease. Here, we review the occurrence and properties
      of repeats in the genome. The different groups of disorders and possible
      pathogenic mechanisms are summarized. In addition, methods used for detection and
      identification of expanded repeats and the related disorders are discussed.

PMID- 12194386
TI  - Hereditary spastic paraplegia: genetic heterogeneity and genotype-phenotype
      correlation.
AB  - Hereditary spastic paraplegia (HSP) is a group of disorders whose primary symptom
      is insidiously progressive, lower extremity spasticity and weakness.
      Neuropathological analysis of "pure" HSP reveals axonal degeneration that is
      maximal in the terminal portions of the longest descending and ascending tracts
      (crossed and uncrossed corticospinal tracts to the legs and fasciculus gracilis,
      respectively). HSP may be transmitted as an X-linked, autosomal recessive, or
      autosomal dominant trait, each of which is genetically heterogeneous: mutations
      in different genes cause clinically similar disorders. To date, there are at
      least three genetic loci for X-linked HSP; at least three genetic loci for
      autosomal recessive HSP; and at least six genetic loci for autosomal dominant
      HSP. The genetic basis for three of these twelve forms of HSP have been
      discovered. One form of autosomal recessive HSP (on chromosome 16) is due to
      mutations in the paraplegin gene, which encodes a mitochondrial protein
      homologous to metalloproteases. One form of X-linked HSP is caused by mutations
      in the proteolipoprotein gene, an intrinsic myelin protein. Mutation in this gene
      also causes the dysmyelinating disorder, Pelizeaus-Merzbacher disease. X-linked
      spastic paraplegia can be caused also by mutations in the L1CAM gene. This review
      summarizes our current understanding of genetic heterogeneity and genotype
      phenotype correlation in HSP.

PMID- 12194387
TI  - Friedreich's ataxia: clinical aspects and pathogenesis.
AB  - Friedreich's ataxia is the most frequent inherited ataxia in Caucasians. It is
      caused by deficiency of frataxin, a highly conserved nuclear-encoded protein
      localized in mitochondria. The DNA abnormality found in 98% of Friedreich's
      ataxia chromosomes is the unstable hyperexpansion of a GAA triplet repeat in the
      first intron of the frataxin gene. Most patients are homozygous for this repeat
      expansion. The expanded GAA repeat causes frataxin deficiency because it
      interferes with the transcription of the gene by adopting a non-B (probably
      triple helical) structure. Longer repeats cause a more profound frataxin
      deficiency and are associated with earlier onset and increased severity of the
      disease. Molecular testing has shown that the phenotypic spectrum of Friedreich's
      ataxia is wider than previously thought. Up to 10% of patients with recessive or
      sporadic degenerative ataxia who do not fulfill the Friedreich's ataxia
      diagnostic criteria are homozygous for expanded alleles at the Friedreich's
      ataxia locus. Late age of onset, retained tendon reflexes, and lack of pyramidal
      signs are among the atypical features observed in some patients with a positive
      molecular test. Yeast cells deficient in the frataxin homologue accumulate iron
      in mitochondria and show increased sensitivity to oxidative stress. This suggests
      that Friedreich's ataxia is caused by mitochondrial dysfunction and free radical
      toxicity, with consequent mitochondrial damage, axonal degeneration, and cell
      death.

PMID- 12194388
TI  - Progress toward gene therapy of Duchenne muscular dystrophy.
AB  - Duchenne muscular dystrophy (DMD) is a common lethal disease for which no
      effective treatment is available. The lethal consequences of DMD are caused by
      absence of a structural protein, called dystrophin, from skeletal and cardiac
      muscle cells. The usefulness of gene replacement as therapy for this disease has
      been established in transgenic mouse models. Unfortunately, progress toward
      therapy for human patients has been limited by the characteristics of currently
      available viral vectors and by lack of a suitable technique for delivery of such
      vectors to a large mass of muscle cells. Successful gene therapy of DMD will
      require a vector that can carry most of the dystrophin coding sequence, that can
      be cheaply produce in large quantities, that can be delivered to a large mass of
      muscle cells, and that provides stable expression of dystrophin after delivery.
      We and others have worked to develop such a vector through modification of
      adenoviruses (Ad). Here we review the characteristics of conventional Ad vectors
      and new helper-dependent, or gutted, Ad vectors. Gutted Ad vectors contain cis
      acting DNA sequences necessary for viral replication and packaging, but are
      deleted, or gutted, for all viral coding sequences. We found that gutted vectors
      efficiently delivered full-length dystrophin to the skeletal muscles of
      dystrophic (mdx) mice. Dystrophic muscles injected with these vectors expressed
      dystrophin for at least four months post-injection, which was the longest time
      point tested. These data suggest that gutted vectors will allow delivery and long
      term expression of dystrophin.

PMID- 12194389
TI  - Dissociative amnesia after general anesthesia--a case report.
AB  - Psychogenic unconsciousness is a rare cause of failure of prompt recovery from
      general anesthesia. The diagnosis is only made by exclusion of other conditions.
      We describe a young, healthy female who failed to wake up promptly after total
      intravenous anesthesia with alfentanil and propofol. She regained consciousness
      24 hours later without any specific treatment. However she sustained amnesia for
      a period of 48 hours. Dissociative disorder was diagnosed after an extensive
      workup. This case report emphasizes the importance of inclusion of psychiatric
      disorder in the differential diagnosis should unexplainable delayed emergence
      from general anesthesia occur.

PMID- 12194390
TI  - Use of corticosteroids in anesthesia and critical care.

PMID- 12194391
TI  - A 'membrane in syringe' technique that allows identification of the epidural
      space with saline while avoids injection of air into the epidural space.
AB  - BACKGROUND: The 'MEMBRANE IN SYRINGE' technique is, in principle, a modification
      of the loss of resistance technique for identifying the epidural space in
      epidural anaesthesia. A plastic membrane is placed halfway inside a syringe
      dividing the syringe into two compartments. The saline compartment encompasses
      the nozzle of the syringe (the distal compartment). The plunger is installed in
      the opposite half of the hallow cylinder. Air is trapped in the space between the
      membrane and the rubber plunger (air compartment). METHODS: There were altogether
      20 epidural procedures to put to the test for this technique. The time spent in
      the undertaking of the procedure, the amount of normal saline injected, whether
      there was a feel of loss of resistance with wrinkling of the membrane in the
      syringe, inadvertent puncture of the dura, the level of epidural block and the
      insertion depth of epidural needle were recorded. RESULTS: The procedure took
      less than 4 minutes to complete in most of the cases. There was no inadvertent
      dural puncture. The average amount of normal saline injected was less than 1 ml.
      In 3 cases, despite the absence of the feel of loss of resistance the epidural
      space was still successfully identified by visible wrinkling of the membrane in
      the syringe. All catheters were inserted smoothly through the epidural needle and
      appropriate level of anesthesia was achieved in all the cases. CONCLUSIONS: The
      advantage of this technique is twofold. Firstly when the syringe is filled with
      both normal saline and air, it can prevent injection of the air into the epidural
      space during identification while at the same time it does not molest the feel of
      compressibility. Secondly, with the membrane separating the normal saline and
      air, correct placement of the needle tip can also be ascertained with loss of
      resistance while, as will be seen, the plastic membrane will wrinkle when saline
      is released into the epidural space.

PMID- 12194392
TI  - The effect of IVPCA morphine on post-hysterectomy bowel function.
AB  - BACKGROUND: Although morphine has been shown to induce bowel dysfunction in a
      dose-dependent fashion, in most relevant studies it was investigated in single
      bolus injection. Recently, intravenous morphine via patient-controlled analgesia
      (IVPCA) has been widely used to provide analgesia by divided bolus doses on
      patients' demand with satisfactory effects. This approach, by reducing the peak
      serum surge, largely resembles the pharmacokinetic and pharmacodynamic advantage
      of continuous infusion. There is yet no report on the investigation of its effect
      on post-operative bowel dysfunction. METHODS: Fifty-one women who underwent
      abdominal total hysterectomy (ATH) due to uterine myoma were enrolled to
      investigate the association between the doses of morphine consumption by PCA and
      the time of first passage of flatus. In all patients morphine was administered
      intravenously via a PCA pump immediately after recovery from general anesthesia.
      RESULTS: We found that 49 out of 51 patients (96%) exhibited mild pain with IVPCA
      morphine. They had consumed an average dose of 16.9 mg morphine (range, 0-46 mg)
      upon the first passage of flatus which occurred 2036.4 min (average) post
      operatively. There was no correlation between the dose of morphine and the time
      of first passage of flatus (r = 0.053, P > 0.05). CONCLUSIONS: The absence of
      suppression of bowel movement by IVPCA morphine for post-operative pain control
      suggests that favorable pharmacokinetic profile of IVPCA can help reduce the
      morphine-induced bowel dysfunction at its therapeutic level.

PMID- 12194393
TI  - Can neostigmine reduce propofol injection pain?
AB  - BACKGROUND: Neostigmine has been found to cause peripheral analgesia. We used
      venous retention technique to evaluate whether neostigmine displayed peripheral
      analgesic effect in reducing propofol injection pain. METHODS: In a double blind
      fashion, 105 patients were randomly allocated to receive either 1 ml 0.5 mg
      neostigmine (Group N, n = 35), 1 ml 2% lidocaine (Group L, n = 35), or 1 ml
      normal saline (Group C, n = 35) as pretreatment to reduce pain on propofol
      injection. A pediatric T-connector linking with the i.v. catheter port was used
      for injection. Venous occlusion was made possible with a tourniquet before the
      intravenous administration of one of the three drugs. The tested drug was allowed
      to retain for one minute and then the tourniquet was released for propofol
      injection. Pain and side effect assessments were made after propofol injection.
      RESULTS: The incidence of propofol injection pain was 85% in normal saline group,
      46% in neostigmine group and 6% in lidocaine group (P < 0.05 among groups). The
      tested drugs arrayed in order of increasing magnitude of intensity of pain upon
      propofol injection were lidocaine (mean rank 34.20), neostigmine (mean rank
      50.42) and normal saline (mean rank 76.81) in sequence (P < 0.05 among groups).
      CONCLUSIONS: With one-minute venous retention, 0.5 mg neostigmine (1 ml) could
      produce peripheral analgesia to some degree in reducing propofol injection pain.
      However, its analgesic effect was inferior to 1 ml of 2% lidocaine.

PMID- 12194394
TI  - An evidence-based review on the use of corticosteroids in peri-operative and
      critical care.
AB  - With complex and extensive pharmacological effects, corticosteroids are widely
      used in many clinical situations. A survey conducted to define the role of
      corticosteroids in various settings of peri-operative and critical care gave
      strong evidence to support that the use of corticosteroid is absolutely indicated
      in patients with adrenal insufficiency, asthma, anaphylaxis, acute spinal cord
      injury, and increased ICP resulting from brain tumors. As the benefits of
      corticosteroids are much in evidence, their uses are recommended to extend to
      postoperative antiemesis, acute respiratory failure (such as ARDS, COPD, and fat
      embolism), increased ICP associated with brain abscess, thyroid storm, and
      refractory hypothermia. Beneficial effect could be expected in septic shock with
      high-dose corticosteroids. Despite extensive reports on their versatile
      usefulness, evidence-based review did not recommend the use of corticosteroids in
      increased ICP associated with traumatic head injury and cerebral infarct, cardiac
      arrest, post-extubation airway edema, and aspiration pneumonia due to poor
      effectiveness let alone further worsening of the conditions. Great caution must
      be taken in clinical situations where administration of corticosteroids is
      considered contraindicated such as systemic fungal infection, hypersensitivity to
      the drug, intramuscular injection in idiopathic thrombocytopenia purpura,
      vaccination with live virus.

PMID- 12194395
TI  - Transesophageal echocardiographic monitoring of critical left ventricular outflow
      tract obstruction following mitral xenograft replacement--a case report.
AB  - Left ventricular outflow tract obstruction (LVOTO) is a critical complication
      after mitral bioprosthesis. Intraoperative transesophageal echocardiographic
      (TEE) monitoring enables early diagnosis and guides prompt subsequent treatment.
      Here we report a case of mitral heart disease who developed critical LVOTO
      following mitral xenograft replacement. The values of intraoperative TEE in the
      disclosure of the LVOTO and its facilitation of successful management are
      discussed.

PMID- 12194396
TI  - Intraoperative aortic dissection--a case report.
AB  - Intraoperative aortic dissection is a rare but potentially fatal complication of
      cardiac surgery. Prompt recognition and repair are necessary to limit the extent
      of dissection to minimize morbidity and mortality. Here, we present a case of
      acute type A dissection of ascending aortic artery occurring after removal of
      aortic cannula at the end of cardiopulmonary bypass. The surgeon immediately
      recannulated him at the femoral artery and repaired the dissection under deep
      hypothermia. Ascending aorta was replaced with Hemashield graft and venous graft
      was reimplanted. Unfortunately, the patient expired the following day due to
      cardiac tamponade resulting from uncontrolled bleeding. Long-standing severe
      hypertension, severe atherosclerotic change of the aortic wall, thin and dilating
      ascending aorta and cystic medial necrosis or collagen vascular disease were
      thought to predispose him to this complication. Gentle manipulation and surgical
      discreetness to forestall aoratic injury could minimize the risk of
      intraoperative aortic dissection. Once aortic dissection has been suspected,
      prompt application of transesophageal echocardiography to confirm the diagnosis,
      and rapid as well as appropriate surgical management are necessary to grasp a
      better outcome.

PMID- 12194397
TI  - Contralateral neurologic deficits following microvascular decompression surgery-
      a case report.
AB  - Microvascular decompression (MVD) surgery for trigeminal neuralgia (Jannetta
      operation) is common in our institution, and postoperative complications are
      uncommon. However, a 46 year-old obese female who underwent MVD surgery for right
      trigeminal neuralgia suffered from postoperative neurologic deficits consisting
      of left facial palsy, left total deafness, weakness and numbness of the left arm,
      and unsteady gait. Here, we bring forth the patient's postoperative events, such
      as delayed emergence, postoperative convulsions, pneumocephalus, and probable
      causes of the neurologic deficits for discussion.

PMID- 12194398
TI  - Continuous cerebrospinal fluid drainage using a lumbar subarachnoid catheter for
      cerebrospinal fluid rhinorrhea after functional endoscopic sinus surgery.
AB  - Anesthesiologists are frequently consulted for performing lumbar cerebrospinal
      fluid (CSF) drainage to facilitate surgery or manage complications. Functional
      endoscopic sinus surgery (FESS) is a common treatment for chronic sinus diseases.
      Cerebrospinal fluid (CSF) leakage is a serious complication following FESS and is
      typically treated with an endonasal free or rotational mucoperichondrial flap.
      Continuous drainage of CSF with a lumbar subarachnoid catheter has been used in
      patients who have undergone neurosurgery but it is seldom used in the treatment
      of post-FESS CSF rhinorrhea. We present a 71-year-old male patient who suffered
      from CSF rhinorrhea after FESS, and was treated successfully with continuous
      lumbar CSF drainage. We are of the opinion that continuous CSF drainage with a
      lumbar subarachnoid catheter is an effective and safe modality of treatment for
      post-FESS CSF leakage.

PMID- 12194399
TI  - What knowledge is relevant to social work practice? The case of TANF
      reauthorization.

PMID- 12194400
TI  - Federalism and social justice: implications for social work.
AB  - Federalism is a system of government that divides power between two or more
      levels of government. During the current conservative political climate in the
      United States, power has shifted increasingly from the federal government to
      states, a move that has implications for the achievement of social justice.
      Consequently, it is now necessary for social workers to engage in political
      activity at the state and local levels, in addition to the federal level, to
      promote social justice. Implications for social work policy practice, research,
      and education for advancing social justice within the federal system of
      government are explored.

PMID- 12194401
TI  - Innovation in social policy: collaborative policy advocacy.
AB  - In a time of policy devolution, social workers have a unique opportunity to
      develop a significant voice in constructing state social welfare policy. This
      article examines a method of collaborative policy advocacy led by social work
      researchers, practitioners, advocates, and students. It is illustrated with a
      five-year project to reduce wealth inequality through community economic
      development. Researchers brought expertise in ideas and analysis to real-world
      applications. Social work practitioners brought essential "on the ground"
      expertise. Students brought much-needed assistance and a fresh perspective to the
      social policy process. Advocates, working in social welfare advocacy
      organizations, bridged these perspectives and provided experience in policy
      advocacy. Working with coalition partners, social workers successfully placed
      asset-based community economic development strategies on the state agenda and
      were instrumental in passage of innovative legislation. The article demonstrates
      that the policy-making process is open to influence by social workers, especially
      if they come prepared with innovative and promising ideas about long-standing
      social issues. Social workers can and should take the lead and become significant
      actors in state policy development.

PMID- 12194402
TI  - Charitable choice and faith-based welfare: a call for social work.
AB  - The Personal Responsibility and Work Opportunity Reconciliation Act of 1996
      contains a little known section referred to as "Charitable Choice." This section
      encourages states to involve community and faith-based organizations in providing
      federally funded welfare services. Most social workers are unfamiliar with this
      part of the legislation and its far-reaching implications for society as a whole
      and for the social work profession as it opens the door for mixing religion and
      publicly supported social services provision. This article reviews how Charitable
      Choice has shifted the way government engages faith-based organizations in social
      services delivery. A review of the public discourse and research findings
      regarding the relevance and implementation of Charitable Choice is also
      presented. Implications for social work are discussed, and a call for social work
      involvement is made.

PMID- 12194403
TI  - Welfare use as a life course event: toward a new understanding of the U.S. safety
      net.
AB  - What proportion of the American population uses a social safety net program
      during the course of adulthood? To address this question, we constructed a series
      of life tables using 30 years of longitudinal data. Our results indicate that two
      thirds of Americans between the ages of 20 and 65 will at some point reside in a
      household that receives benefits from a means-tested welfare program (food
      stamps, Medicaid, Supplemental Security Income, Aid to Families with Dependent
      Children, or other cash welfare). Such assistance is often in the form of in-kind
      programs, such as food stamps or Medicaid. The findings also indicate that the
      use of welfare tends to take place over fairly short intervals of time. For
      example, although 65 percent of Americans will use welfare by age 65, only 15.9
      percent will do so for five or more consecutive years. However, once the use of
      welfare occurs, it is quite likely to occur again at some point during adulthood.
      Our results suggest that, contrary to conventional wisdom, the use of the United
      States social safety net is a mainstream experience.

PMID- 12194404
TI  - Changing safety net of last resort: downsizing general assistance for employable
      adults.
AB  - General assistance (GA) has served as an income support program of last resort
      for people not eligible for other programs. Because each state has complete
      discretion to design its program, the GA services model parallels Temporary
      Assistance for Needy Families (TANF) in its reliance on decentralized government
      decision making. Thus, GA programs can provide lessons about services variability
      and common program features that have arisen in a decentralized income support
      system. This study examined the characteristics of state GA programs across
      several program dimensions--eligibility criteria, work requirements, time limits,
      administrative arrangements, and caseloads. The authors show that GA programs
      have changed from 1989 to 1998. Although most states retained GA programs in some
      form, caseloads declined as a result of tightening eligibility requirements for
      people considered employable. This casts doubt on the viability of GA as a safety
      net program for economically vulnerable people, including those who do not
      qualify for or exceed time limits under TANF.

PMID- 12194405
TI  - What social workers need to know about the earned income tax credit.
AB  - Over the past decade, the federal earned income tax credit (EITC) has become the
      largest antipoverty program in the United States. For the 2002 tax year, working
      families with children can receive as much as $4,140 in EITC benefits. Although
      families may arrange to receive benefits throughout the year (through their
      paychecks), most receive a lump sum after filing federal income taxes. Research
      suggests that many families use the credit to purchase big-ticket items, to move,
      to pay for educational expenses, or to set aside savings. Thus, the credit may
      promote long-term household development as well as help families with basic
      expenses. Research also suggests that EITC encourages work among single-parent
      families, an outcome that is consistent with one goal of welfare reform. Social
      workers can be involved in outreach efforts that help low-income workers claim
      EITC benefits and inform them about advance-payment options. Social workers can
      also support efforts to increase EITC benefits for larger families and link tax
      refunds to saving programs.

PMID- 12194406
TI  - Living on the edge: examination of people attending food pantries and soup
      kitchens.
AB  - This article presents information from a study of people receiving food
      assistance services from food pantries and soup kitchens in Virginia. The data
      indicate that significant numbers of individuals and families--many of whom are
      employed--are seeking food assistance. Many of these individuals also have been
      homeless, victims of domestic violence, unable to pay their utility bills, or
      have lost their public benefits. A critical issue raised by the findings is the
      low rate of participation in the food stamp program. Fewer than 40 percent of the
      respondents were receiving food stamps. Although the food stamp program is
      intended to help households buy a nutritionally adequate diet, there is growing
      concern that a large segment of low-income Americans are slipping through this
      safety net. The article concludes with suggestions for social work interventions
      to address issues of food security.

PMID- 12194407
TI  - TANF: what went wrong and what to do next.
AB  - The Temporary Assistance for Needy Families (TANF) program, widely heralded as
      the "end to welfare as we know it," is in its sixth year of implementation.
      According to many, the welfare debate has been settled, and both legislators and
      the public have proclaimed the program a success. This article examines the
      accumulated data on the effect of welfare reform, which shows, contrary to
      popular opinion, the goal of self-sufficiency remains elusive for many, and poor
      women and their families are being hurt, not helped, by TANF. It is argued that
      the booming economy and consequent expanding labor market have led to the
      perceived success of TANF and that the optimism expressed about dwindling welfare
      rolls is misplaced. The failure of TANF to adequately address obstacles to self
      sufficiency in the workplace threatens to create an even worse welfare problem in
      the future. During the TANF evaluation period, social workers are urged to take a
      more active role in urging TANF modifications.

PMID- 12194408
TI  - Dynamics of income packaging: a 10-year longitudinal study.
AB  - This article examines the methods and dynamics of packaging multiple sources of
      wage and nonwage income as a means of making ends meet over a 10-year period
      among a sample of displaced steelworkers who lost jobs as a result of plant
      closings in the 1980s and then experienced extensive downward mobility. The study
      tracked changes in the respondents' income and employment over a decade, the
      dynamics of their use of social services, their pooling of a variety of income
      sources, and the use of social assistance to supplement low wages. The study
      found that among this sample income packaging was a universal economic strategy
      and that use of social services did not affect later employment and earnings.

PMID- 12194409
TI  - Social work advocacy in the post-TANF environment: lessons from early TANF
      research studies.
AB  - This study examined early research findings concerning the well-being of people
      who leave Temporary Assistance for Needy Families (TANF) programs and then
      applies these findings in the development of TANF-related advocacy strategies.
      Based on secondary data analysis of TANF leaver studies from 12 states with large
      TANF caseloads, the authors focus on the employment and earnings experiences of
      leavers; TANF recidivism and its relationship to job stability; and the use of
      support services. State studies typically have found employment levels among
      leavers in the 55 percent to 65 percent range, but average earnings fall below
      the poverty level. Although those who remain employed can expect earnings growth,
      job instability is a significant problem and contributes to TANF recidivism rates
      of 21 percent to 35 percent within the first year. Available support services
      such as Medicaid, food stamps, and child care subsidies are underused, often
      because leavers do not understand that they are eligible. Recommended advocacy
      strategies include policy interventions to improve the economic well-being of low
      income working people, as well as administrative and direct practice strategies
      to improve the implementation of existing policies. The authors argue that
      attention to such advocacy efforts is both critical and opportune for social
      work, given the profession's historical mission, impending federal TANF
      reauthorization, and unspent TANF allocations.

PMID- 12194410
TI  - Voicing realities and recommending reform in PRWORA.
AB  - This article represents the views of 12 women facing welfare reform under the
      Personal Responsibility and Work Opportunity Reconciliation Act of 1996 and 12
      services providers of two state offices from a midwestern metropolitan area. The
      author used constructivist inquiry to understand their multiple constructions of
      reality associated with the "work first" provision of the law. Three aspects of
      work are discussed: preparation for work, nature of work, and consequences of
      work. The women and the services providers had some commonalities as well as
      differences in their perceptions about work first and their recommendations for
      changes. Although all the women facing reform identified some negative
      attributions of work first, not all services providers expressed negative views
      about work first. A majority of the women and a few services providers
      recommended that women need access to education and training to get better jobs
      and that they need more incentives to work. However, both groups recommended that
      they be included in future welfare reform decision making. Social workers need to
      carry these voices to the federal policymakers before this law is reauthorized in
      2002.

PMID- 12194412
TI  - An ounce of forgiveness is better than a ton of revenge: a reflection on the
      September 11 terrorist attacks.

PMID- 12194411
TI  - Response to Co-constructing cooperation with mandated clients.

PMID- 12194413
TI  - The importance of temperature in assessing iron pipe corrosion in water
      distribution systems.
AB  - Temperature is expected to play a significant role in the corrosion of iron pipes
      in drinking water distribution systems. Temperature impacts many parameters that
      are critical to pipe corrosion including biological activity, physical properties
      of the solution, thermodynamic and physical properties of corrosion scale, and
      chemical rates. Moreover, variations in temperature and temperature gradients may
      give rise to new corrosion phenomena worthy of consideration by water treatment
      personnel.

PMID- 12194414
TI  - An investigation on biological stability of product water generated by lab-scale
      and pilot-scale distillation systems.
AB  - Lab-scale and pilot-scale distillation systems were assessed in this study and
      the effectiveness of the treatment processes on Assimilable Organic Carbon (AOC)
      removal was also investigated. Seawater as one of the alternative water sources
      was used as the feed water and the resulting product water was intended for
      industry use. Acidification, ion trapping and anti-scaling chemical dosing were
      adopted as the pre-treatment processes to the feed water before distillation for
      pilot-plant system. The AOC assay was used to evaluate the efficiencies of
      various unit processes for AOC removal. Heterotrophic Plate Counts (HPC) was
      adopted in conjunction with AOC to determine the biological stability of the
      water samples. It is noted that the distillation system was able to produce a
      product water with an acceptable AOC concentration of less than 20 micrograms
      acetate-C L-1. This would suggest that the distillation system was capable of
      delivering a biologically stable product water. The results from lab-scale system
      indicated that pretreatment such as acidification, chlorination and antiscalant
      would increase AOC, although this does not affect the general performance of
      distillation system.

PMID- 12194415
TI  - Metals in tissues of diamondback terrapin from New Jersey.
AB  - Relatively little is known about contaminants in reptiles, particularly turtles.
      The distribution of metals in eggs, liver and muscle of diamondback terrapin
      (Malaclemys terrapin) was examined from Barnegat Bay, New Jersey as part of an
      aquatic study to understand movement of contaminants in the bay. Lead and cadmium
      were relatively low in all tissues. There were significant differences among
      tissues for all metals, except lead. Where there were significant differences,
      levels were highest in the liver, except for chromium. Levels of mercury were 6.6
      times higher in the liver than muscle, and manganese levels were 4 times as high.
      The levels of metals in muscle of diamondback terrapin are below those that might
      cause effects in consumers, including humans who eat them in stews. However, the
      level of mercury in liver is sufficiently high to be problematic for consumers
      and scavengers that eat liver.

PMID- 12194416
TI  - Development of a provisional physical habitat index for Maryland freshwater
      streams.
AB  - Provisional physical habitat indices were developed and validated for Maryland
      Coastal and Non-Coastal Plain streams using variables (commonly called metrics)
      that best discriminated reference and degraded conditions based on biological,
      chemical and land use data from the 1994-97 Maryland Biological Stream Survey
      (MBSS). These habitat indices contained variables that described structural,
      hydrological, vegetative and aesthetic components of stream habitat. Variables
      with the best discriminatory power for Coastal Plain streams were: instream
      habitat, velocity/depth diversity, pool/glide/eddy quality, embeddedness, maximum
      depth and aesthetic rating. Physical habitat variables with the best
      discriminatory power for Non-Coastal Plain sites were: instream habitat,
      velocity/depth diversity, riffle/run quality, embeddedness, number of rootwads
      and aesthetic rating. The overall classification efficiency for index validation
      was 76% for both indices pooled over both strata. Scaled physical habitat index
      values (0-100) for both strata identified nearly twice as many good sites (31%)
      as very poor sites (16%). More than half the Maryland sites were in the poor to
      fair range (53%).

PMID- 12194417
TI  - Microbiological characteristics in a zero-valent iron reactive barrier.
AB  - Zero-valent iron (Fe0)-based permeable reactive barrier treatment has been
      generating great interest for passive groundwater remediation, yet few studies
      have paid particular attention to the microbial activity and characteristics
      within and in the vicinity of the Fe0-barrier matrix. The present study was
      undertaken to evaluate the microbial population and community composition in the
      reducing zone of influence by Fe0 corrosion in the barrier at the Oak Ridge Y-12
      Plant site. Both phospholipid fatty acids and DNA analyses were used to determine
      the total microbial population and microbial functional groups, including sulfate
      reducing bacteria, denitrifying bacteria, and methanogens, in groundwater and
      soil/iron core samples. A diverse microbial community was identified in the
      strongly reducing Fe0 environment despite a relatively high pH condition within
      the Fe0 barrier (up to pH approximately 10). In comparison with those found in
      the background soil/groundwater samples, the enhanced microbial population ranged
      from approximately 1 to 3 orders of magnitude and appeared to increase from
      upgradient of the barrier to downgradient soil. In addition, microbial community
      composition appeared to change over time, and the bacterial types of
      microorganisms increased consistently as the barrier aged. DNA analysis indicated
      the presence of sulfate-reducing and denitrifying bacteria in the barrier and its
      surrounding soil. However, the activity of methanogens was found to be relatively
      low, presumably as a result of the competition by sulfate/metal-reducing bacteria
      and denitrifying bacteria because of the unlimited availability of sulfate and
      nitrate in the site groundwater. Results of this study provide evidence of a
      diverse microbial population within and in the vicinity of the iron barrier,
      although the important roles of microbial activity, either beneficially or
      detrimentally, on the longevity and enduring efficiency of the Fe0 barriers are
      yet to be evaluated.

PMID- 12194418
TI  - Development and evaluation of the Lake Macroinvertebrate Integrity Index (LMII)
      for New Jersey lakes and reservoirs.
AB  - In response to the recent focus by the U.S. Environmental Protection Agency on
      bioassessment of lakes, a multimetric index was developed for New Jersey lakes
      and reservoirs using benthic macroinvertebrates. Benthic samples were collected
      from reference and impaired lakes with muck and intermediate sediments in central
      and northern New Jersey during summer 1997. We used a stepwise process to
      evaluate properties of candidate metrics and selected five for the Lake
      Macroinvertebrate Integrity Index (LMII): Hilsenhoff Biotic Index (HBI), percent
      chironomid individuals, percent collector-gatherer taxa, percent
      oligochaetes/leeches, and number of Diptera taxa. We scored metrics as the
      fraction of the best expected value (based on all sites) achieved at a site and
      summed them into the LMII. Evaluation of the LMII showed that it discriminated
      well between reference and impaired lakes and was strongly related to several
      potential stressors. Chemical and physical gradients distinguished between
      reference and impaired lakes, and the LMII summarized these gradients well. The
      LMII corresponded strongly with land use, but some lakes with more urban land use
      still achieved high scores. Based on a power analysis, the ability of the LMII to
      detect differences in condition was sensitive to the number of samples from each
      lake.

PMID- 12194419
TI  - Integrative aspects of problem theory: a review of applications.
AB  - It is argued that people work on 6 interrelated general problems, called key
      problems, which are necessarily simply conceived and therefore open to a priori
      identification. Key problems demand separate attention, and, with children below
      9 years of age and again between 10 and 17 years of age, and with adults in long
      term groups, they receive attention 1 by 1, as focal problems, with intervening
      transitional phases, in a fixed sequence. Isolated societies stress 1 focal
      problem, and families and individuals tend to do the same. Humor and elated play
      worsen the problem. Brain lateralization helps in separating work on the 1st key
      problem from work on other problems, and failure to accomplish this contributes
      to mental disorder. The theory can be fitted to aspects of brain activity (as
      shown in the electroencephalograph), such as the change with age in theta
      coherence growth rate.

PMID- 12194420
TI  - Quality of relationships and structural properties of social support networks of
      female survivors of abuse.
AB  - The purposes of this study were to examine the structural properties of the
      social support networks of female survivors of violence and abuse and to
      investigate the quality of the relationship, and specific level of satisfaction,
      survivors have with their social support networks. Participants averaged 5.8
      persons in their social support networks. Their levels of satisfaction with the
      emotional, practical, financial, guidance, and socializing support they received
      from members of their social support networks were higher with respect to close
      friends and coworkers than with respect to family members and professionals
      (e.g., attorneys and social workers). The most common type of support provided by
      close friends who were themselves victims of abuse was emotional, guidance, and
      socializing support, and the most satisfying support was the financial and
      practical help that came from parents or family. An interesting finding was the
      significant presence of men in the survivors' social support networks. Overall
      satisfaction with the quality of support from the social support networks was
      high, and satisfaction with support from men was comparable, if not higher, than
      support from women. Multiple regression models revealed that satisfaction with
      support networks was a potent predictor of self-esteem, emotional health, and
      loneliness. Intimacy, especially in terms of exclusiveness and trust or loyalty,
      with at least a few members of the support network contributed significantly to
      the variance in self-esteem, emotional health, and loneliness among the abused
      women. The size of the support network also emerged as a limited contributor to
      well-being. Implications and applications are discussed for professionals working
      with female survivors of abuse.

PMID- 12194421
TI  - Rigidity of thought and behavior: 100 years of research.
AB  - Rigidity is one of the oldest psychological constructs, with systematic research
      dating back to the late 19th century. The authors review this research in an
      attempt to clarify the construct of rigidity and to investigate its correlates.
      Rigidity is described as a multidimensional construct encompassing the tendency
      to form and perseverate in the use of mental and behavioral sets. A series of
      meta-analyses was performed based on three measures of behavioral rigidity: the
      Einstellung Water-Jar Task, the Wisconsin Card Sorting Task, and the motor
      cognitive dimension of the Test of Behavioral Rigidity. The results indicated
      that rigidity is curvilinearly related to age, positively related to
      authoritarianism (particularly under stressful situations), and negatively
      related to intelligence; that men are more rigid than women; that obsessive
      compulsiveness is positively related to rigidity; and that schizophrenics are
      more rigid than nonschizophrenic siblings and normal controls. Unresolved issues
      and gaps in the research are discussed.

PMID- 12194422
TI  - Vaccine preventable diseases and vaccination coverage in Australia, 1999 to 2000.

PMID- 12194423
TI  - Steroids in arms: science, government, industry, and the hormones of the adrenal
      cortex in the United States, 1930-1950.

PMID- 12194424
TI  - Early nursing reform in nineteenth-century London: a doctor-driven phenomenon.

PMID- 12194425
TI  - Twixt candle and lamp: the contribution of Elizabeth Fry and the Institution of
      Nursing Sisters to Nursing Reform.

PMID- 12194426
TI  - "Clone": the history of a euphonious scientific term.

PMID- 12194428
TI  - Medieval demographic thought. Essay review.

PMID- 12194427
TI  - An epidemiologist at work: the personal papers of Sir Richard Doll.

PMID- 12194429
TI  - Development of gluconeogenic enzymes in fetal sheep liver and kidney.
AB  - In the sheep, the system of enzymes necessary for conversion of nonhexose
      substrates to glucose becomes active during late fetal life. Glucose-6
      phosphatase and fructose-1,6-diphosphatase, two of the four key gluconeogenic
      enzymes, appear in significant amounts between 100 and 120 days gestation.
      Phosphoenolpyruvate carboxykinase activity is comparable to mature animals as
      early as 45 days gestation. Two aminotransferases, necessary to allow amino acid
      access to the gluconeogenic pathway, likewise have substantial activity as early
      as 45 days gestation. Hence, the surge of glucose-6-phosphatase and fructose-1,6
      diphosphatase at 100-120 days gestation makes possible the endogenous production
      of new glucose by fetal sheep at a time when the amount of glucose transferred
      from the maternal circulation is less than the total aerobic substrate utilized
      by the fetus. Both renal cortex and liver have similar developmental patterns for
      the gluconeogenic enzymes, although renal cortex generally shows greater activity
      than liver. This observation holds true for tissue from both fetal and mature
      animals.

PMID- 12194430
TI  - Periodic movements of Dictyostelium discoideum sorocarps.
AB  - We report periodic movements during erection of Dictyostelium discoideum (Dd)
      sorocarps. Our observations lead to the working hypothesis that Dd sorocarp
      erection occurs by two superimposed processes: one periodic, with a modal period
      of 6 1/2 min, and one continuous. We tentatively identify the periodic process
      with cell movement into the apex of the Dd stalk, and the continuous process with
      cell vacuolation, together with stalk sheath extension.

PMID- 12194431
TI  - Chromatin proteins from normal, vegetalized, and animalized sea urchin embryos.
AB  - The chemical composition of the chromatin, the fractional content of histones and
      nonhistone chromatin proteins (NHP), and the biosynthesis of these proteins in
      normal, vegetalized, and animalized embryos of the sea urchin Strongylocentrotus
      droebachiensis at the blastula, mesenchyme blastula, and gastrula stages have
      been studied. The amount of the NHP in the chromatin from normal and vegetalized
      embryos increases during early embryonic development while that in animalized
      embryos remains without change at the mesenchyme blastula stage and then
      decreases. During development the histone content in all three cases slightly
      decreases. Polyacrylamide gel electrophoresis reveals that both fractional
      composition of histones and their biosynthesis in normal, vegetalized, and
      animalized embryos display no differences. During development, however, some
      changes occur, so that the relative amount of histones F1 and F2a2 increases, F2b
      decreases, while F3 and F2a1 remains constant. Histone F1 at the blastula stage
      consists of two subfractions while at the gastrula stage it consists of three
      subfractions. The histone F2a1 consists of one and two, respectively. Histone F3
      at all stages is made up of three subfractions; histone F2b is made up of two;
      and the histone F2a2 is electrophoretically homogeneous. Specific radioactivity
      of the arginine-rich histones F3 and F2a1 tends to increase during development,
      while that of moderately lysine-rich histones F2b and F2a2 does not change, and
      that of the lysine-rich histone F1 decreases. The NHP in normal, vegetalized, and
      animalized embryos at different developmental stages consist of 17 fractions that
      can be separated by isoelectrofocusing within the 4.5-8.8 pH range. Quantitative
      changes have been observed in the fractions focused at pH 4.5-6.1 during
      development and in normal and modified embryos at the gastrula stage.

PMID- 12194432
TI  - Induction of meiosis in fetal mouse testis in vitro.
AB  - Fetal mouse testes and ovaries with their urogenital connections were cultured
      singly or in pairs on Nuclepore filters. When a testis in which the sex was not
      yet morphologically detectable was cultured together with older ovaries
      containing germ cells which were progressing through the meiotic prophase, the
      male germ cells were triggered to enter meiosis. When older fetal testes in which
      the testicular cords have developed were cultured together with ovaries of the
      same age with germ cells in meiosis, the oocytes were prevented from reaching
      diplotene stage. It was concluded that the fetal male and female gonads secrete
      diffusable substances which influence germ cell differentiation. The male gonad
      secretes a "meiosis-preventing substance" (MPS) which can arrest the female germ
      cells within the meiotic prophase. The female gonad secretes a "meiosis-inducing
      substance" (MIS) which can trigger the nondifferentiated male germ cells to enter
      meiosis.

PMID- 12194433
TI  - Regulation of lactate dehydrogenase (LDH) and alcohol dehydrogenase (ADH)
      synthesis in liver nuclei, following their transfer into oocytes.
AB  - The regulatory effect of oocyte cytoplasm on the synthetic activity of
      transferred somatic cell nuclei was studied using an interspecific hybrid
      combination of Ambystoma texanum and Ambystoma mexicanum (axolotl). The enzymes
      lactate dehydrogenase (LDH) and alcohol dehydrogenase (ADH) were used as markers
      of gene activity. In both species of salamanders, LDH is synthesized in the liver
      and oocytes, while ADH is tissue-specific being synthesized in the liver but not
      oocytes. Both LDH and ADH show species-specific patterns on starch gels which
      permit detection of enzymes synthesized by texanum liver nuclei following their
      transfer into axolotl oocytes. Analysis of recipient oocytes after 1-3 weeks in
      culture reveals the presence of newly synthesized texanum LDH but not ADH. These
      results indicate that the transferred texanum liver cell nuclei continue to
      synthesize a product (LDH) found in both liver cells and oocytes, but fail to
      synthesize the liver-specific product (ADH) which is normally absent in oocytes.
      Thus, in the case of ADH and LDH the oocyte cytoplasm appears to be able to
      regulate the synthetic activity of the transferred somatic cell nuclei so as to
      conform to the oocytes' normal synthetic output.

PMID- 12194434
TI  - Projection of sensory neurons from a homeotic mutant appendage, Antennapedia, in
      Drosophila melanogaster.
AB  - Central projections of sensory neurons from homeotic mutant appendages
      (Antennapedia) of Drosophila melanogaster were compared with those of wild-type
      antennae and wild-type legs by means of degeneration and cobalt backfilling
      methods. Sensory axons originating from wild-type thoracic legs terminate within
      the ventral ipsilateral half of the corresponding neuropile segment and do not
      project to the brain. Sensory fibers from the third antennal segment (AIII) of
      wild-type animals project into the ipsilateral antennal glomerulus (AG) and to a
      lesser extent into the contralateral AG, whereas those from the second antennal
      segment terminate principally within the ipsilateral posterior antennal center.
      The sensory terminals of femur, tibia, and tarsi of the homeotic leg show a
      distribution very similar to that of the homologous wild-type antennal segment
      AIII, differing to a minor degree only in the size and precise localization of
      terminals within the antennal glomeruli. No degenerating axons were evident in
      ultrastructural examination of neck connectives after removal of homeotic legs.
      It is thus very improbable that any sensory fibers of the homeotic leg project to
      normal leg projection areas in the thoracico-abdominal ganglion. Several
      alternative explanations are offered for the apparent retention of antennal
      specificity by axons from the transformed appendage.

PMID- 12194435
TI  - Use of preformed cell aggregates and layers to measure tissue-specific
      differences in intercellular adhesion.
AB  - The binding of aggregates formed from various 7-day chick embryo tissues to
      cultured cell layers was analyzed 24 hr following trypsin dissociation of the
      tissues. The proprotion of aggregates binding is independent of the number of
      aggregates added, and changes with time over 60 min in a manner consistent with a
      first-order process. The adhesive parameter measured, the percentage of
      aggregates binding to cell layers per unit time, varies slightly with aggregate
      size but is not dependent upon the probability of collision of the aggregate with
      the layer. The rate of binding and the effect of modifiers of binding
      (temperature, inhibitors of oxidative metabolism and glutaraldehyde) are
      substantially different for neural retina interactions than for liver or heart
      interactions, suggesting that retina cells may form intercellular bonds via a
      mechanism distinct from that of liver or heart cells. The rate of binding between
      like tissue types is, with one exception, greater than between unlike types.
      Glutaraldehyde treatment of only one of the reactants abolishes this adhesive
      specificity. Aggregate binding provides a means of quantitatively assessing
      intercellular adhesion which has the advantage of reducing the effects of
      trypsinization on measurements of adhesion, and therefore lends itself to the
      investigation of cellular consequences of adhesion.

PMID- 12194436
TI  - Do rates of intercellular adhesion measure the cell affinities reflected in cell
      sorting and tissue-spreading configurations?
AB  - These experiments constitute the first experimental test of the hypothesis that
      the rates of adhesion between cells measure the intensities of adhesion or tissue
      affinities that could explain cell sorting and tissue spreading. For any set of
      relative adhesive intensities between cells in a heterogeneous population, a
      corresponding minimal free energy configuration can be calculated. This is the
      cell distribution toward which both cell sorting and tissue spreading should
      lead. Equilibrium configurations were determined for combinations of 7-day
      embryonic retina (R) with liver (L) and heart (H), both of which became
      completely enveloped by R. To produce these results, the adhesive intensities
      would have to fall in the sequences: L-L > L-R > R-R; and H-H > H-R > R-R. To
      determine whether the rates of adhesion fall into these same sequences, we have
      devised a new technique which measures the rates of adhesion between pairs of
      already-formed cell aggregates of like and unlike kinds. These fall in the
      sequence L-L > or = H-H > L-H > R-R > H-R > L-R. If these rates paralleled the
      corresponding intensities of adhesion at configurational equilibrium, both L and
      H should have become only partially enveloped by R. Thus the rates at which
      adhesions are initiated do not predict the relative adhesive intensities that
      could explain the observed tissue configurations.

PMID- 12194437
TI  - Selective control of fibroblast proliferation and its effect on cardiac muscle
      differentiation in vitro.
AB  - The stability of the differentiated state of cardiac myocytes in vitro was
      examined under culture conditions which selectively stimulated or inhibited
      proliferation of fibroblasts. Regulation of fibroblast proliferation in cultures
      of myocardial cells from 8-day embryonic chicks was achieved by adjustment of the
      glutamine (Gln) concentration in the culture medium (Ham's F-12 medium containing
      2 x amino acids and 5% fetal calf serum). Myocardial cells, when plated at 80
      cells/mm2 in Gln- medium, maintained a stable density of approximately 40% of the
      plating density for more than 30 days. When Gln was added to the medium (292
      micrograms/ml) fibroblast proliferation was stimulated, and by 5-6 days after
      this addition cell densities had increased to confluency. The selective action of
      glutamine on fibroblast proliferation was determined by labeling cultures with
      tritiated thymidine ([3H]TdR) and scoring its incorporation into myocytes and
      fibroblasts by radioautography. After 2 weeks in Gln- medium, the mitotic index
      was 0.3% and the [3H]TdR-labeling index (1.5-hr pulse) was 6.4%. In addition, the
      proportion of myocytes in the population was constant at 64.2% for at least 30
      days in vitro, and contractile activity was observed for up to 6 months. After 5
      days of Gln replacement, the cells exhibited a labeling index of 25%, the
      proportion of myocytes decreased to less than 10% and contractile activity was
      rarely observed. Although the [3H]TdR-labeling index of fibroblasts and myocytes
      was nearly identical in Gln- medium, the addition of Gln produced a fivefold
      stimulation in the fibroblast labeling index, but did not affect myocyte
      proliferation or DNA synthesis. A unique phenomenon of myocyte congregation was
      observed only in Gln- medium which resulted in the formation of myocyte colonies
      from which fibroblasts were largely absent. It is suggested that this process
      with the resultant establishment of a functional electrical syncytium plays a
      significant role in the development and stabilization of myocyte differentiation
      in vitro.

PMID- 12194438
TI  - The possible differentiation of osteogenic elements in vitro from chick limb
      mesodermal cells. I. Morphological evidence.
AB  - In the developing chick limb bud, myogenic, fibrogenic, chondrogenic, and
      osteogenic tissues are derived from embryonic mesenchyme. Previous reports show
      that when stage 24 limb mesenchymal cells are cultured in vitro, chondrocytes,
      fibrocytes, and myocytes can be identified on the basis of morphological and
      biochemical parameters. The studies reported here clearly demonstrate that, in
      similar cultures, crystalline calcium phosphate material is deposited in the
      chondrocytic and fibrocytic matrices. Such crystalline material is not observed
      before Day 10 of culture life. Subsequent to Day 10 of culture, first amorphous,
      then crystalline calcium phosphate is observed. On the basis of light and
      electron microscopic analysis, it appears that the in vitro calcification
      phenomenon closely resembles the morphological and temporal sequence of
      osteogenesis observed in vivo.

PMID- 12194439
TI  - Serum protein synthesis in the early chick embryo.
AB  - Isolated yolk-sacs of chick embryos secreted serum proteins when incubated in
      buffered chick Ringer's solution. The presence of serum transferrin, two embryo
      specific alpha-globulins, and a prealbumin were demonstrated by acrylamide gel
      analysis. Yolk-sacs from embryos explanted at 11-13 somites (40 hr preincubation)
      and cultured for 48 hr secreted in addition a protein with the mobility of serum
      albumin. Incubation of yolk-sacs in the presence of radioactive valine indicated
      that serum proteins were synthesized as early as the primitive streak stage. By
      incubating isolated yolk-sacs and embryos from 48-hr explants in the presence of
      radioactive valine, the synthesis of serum proteins was found to be restricted to
      the yolk-sac at this stage of development. Culturing explants on various nutrient
      proteins as well as protein starvation medium altered the relative synthesis of
      several serum proteins. We have proposed that morphological and biochemical
      changes in embryos resulting from altered nutrition may be mediated by the
      proteins of the serum.

PMID- 12194440
TI  - Two-dimensional gel patterns of protein synthesis before and after fertilization
      of sea urchin eggs.
AB  - Eggs and embryos of the sea urchin Lytechinus pictus were labeled with
      [35S]methionine. Aqueous extracts of protein were prepared and analyzed by a high
      resolution two-dimensional polyacrylamide gel electrophoresis system described
      recently by O'Farrell utilizing isoelectric focusing and sodium dodecyl sulfate
      electrophoresis. Out of about 400 distinctly resolved newly synthesized proteins,
      all but a few detectable in the zygote were being synthesized in the egg. Thus,
      the activation of translation of stored maternal messenger RNA following
      fertilization is due to a quantitative rather than qualitative change in the
      population of messenger RNA available for translation. The patterns of protein
      synthesis change only slightly during cleavage, but major differences appear by
      the beginning of gastrulation.

PMID- 12194441
TI  - Inhibition of oocyte maturation by theophylline: possible mechanism of action.
AB  - Theophylline, a competitive inhibitor of cAMP phosphodiesterase, inhibits the
      maturation of oocytes previously exposed to progesterone. Cyclic AMP levels
      remain constant both during normal maturation and in response to theophylline,
      even though the latter effectively inhibits phosphodiesterase activity in the
      oocyte. Thus, the inhibition is not attributable to elevated cAMP levels. Rather,
      we suggest that theophylline may exert its inhibitory effects on maturation
      either by reducing rates of protein synthesis or possibly through effects at the
      oocyte surface.

PMID- 12194442
TI  - Influences of mother's work, childhood place of residence, and exposure to media
      on breast-feeding patterns: experience of Nigeria and Uganda.
AB  - This study uses data from the Nigerian Demographic and Health Survey collected in
      1990 and the Ugandan Demographic and Health Survey collected in 1995 to examine
      the implications of mother's work, childhood place of residence, and exposure to
      the media for breast-feeding patterns (exclusivity and intensity) in Nigeria and
      Uganda. Nigeria and Uganda present an interesting contrast because Nigeria is
      more modernized and economically developed than Uganda, thus providing a good
      indication of the influence of modernization on breast-feeding patterns. Mother's
      work status is defined by considering whether mothers earned cash from work and
      took their children to work, hence emphasizing the compatibility of work with
      child care. Work least compatible with child care had a negative effect on breast
      feeding intensity in Nigeria. The negative effect of mother's work on exclusive
      breast-feeding (that is, if the mothers used formula or milk instead) observed
      for some working mothers in Nigeria and Uganda was partly confounded by urban
      residence, exposure to media, and other socioeconomic factors. Mother's work did
      not have a negative effect on breast-feeding intensity in Uganda. The
      relationship between mother's work, urban residence, media exposure, and breast
      feeding practice seems to be stronger in Nigeria than Uganda.

PMID- 12194443
TI  - Sociodemographic attributes of Iranian wives who reported unwanted pregnancies.
AB  - In a 1989 Family Planning Study in Iran, 40 percent of the married women of
      reproductive age reported that their last or current pregnancies were unwanted
      and unintended. This finding is consistent with the results obtained from a
      number of studies undertaken in the countries of North Africa and the Middle
      East. Although the phenomenon of unwanted pregnancy is a significant topic in the
      population studies, it has received very little attention. This paper shows the
      differences between two groups: group A, those married women who reported that
      their last or current pregnancies were wanted, and group B, those married women
      who reported that their last or current pregnancies were unwanted. The findings
      of this study clearly show significant differences between these two groups in
      regard to some key sociodemographic attributes: wife/husband's education, actual
      and desired fertility, wife's current age, past and present practice of
      contraceptive methods, and extent of satisfaction with family planning services
      are among the attributes differentiating these two groups. Our examination of
      these variables suggests that group B had higher parity, fertility, less desire
      for more children, less use of contraceptive techniques, and less satisfaction
      with the efficiency of the contraceptive techniques than group A. The
      relationship between education and wanted/unwanted pregnancies is mixed. The
      urban women who wanted pregnancies and were 25 years old or older were more
      educated than those who did not want pregnancies. On the contrary, the rural
      women whose pregnancies were not wanted were more educated than those who wanted
      pregnancies regardless of age, parity, and locality differences. Furthermore, the
      urban/rural women with different levels of parities who did not want to be
      pregnant were more educated than the urban/rural women who wanted pregnancies.
      Finally, the standardized regression coefficients, obtained in logistic
      regression, reveal that among urban women the desire for more children and parity
      are the first and second most significant independent variables differentiating
      between group A and group B. Among rural women, living children and the desire
      for more children were the first and second most important variables
      differentiating between group A and group B.

PMID- 12194444
TI  - A comparative study of determinants of uxorilocal marriage in two counties of
      China.
AB  - A strictly maintained patrilineal family system makes virilocal marriage almost
      universal and uxorilocal marriage rare in the history of rural China. Uxorilocal
      marriage can be divided into two types that may be termed, respectively,
      contingent and institutional. The former preserves family lineages in families
      without a son and occurs when uxorilocal marriage is uncommon. The latter serves
      practical economic purposes in families with sons and occurs when uxorilocal
      marriage is relatively prevalent. Using data from a survey in two counties of
      Shaanxi--Lueyang, where both kinds of uxorilocal marriage are prevalent, and
      Sanyuan, where uxorilocal marriage is rare and usually contingent--this paper
      employs logistic regression models in a quantitative comparative study of
      determinants of uxorilocal marriage in rural China. We show that the purposes and
      prevalence of the two types of uxorilocal marriage differ and that their
      determinants are also different in the two counties. In Sanyuan, the determinants
      are only a couple's sibling composition, membership in a large family clan, and
      educational level. In Lueyang, in addition to those determinants in Sanyuan,
      important contributions to the type of uxorilocal marriage include a couple's
      parental marriage type, age at marriage, adoption status, marriage arrangement,
      and their attitudes toward uxorilocal marriage. The results indicate the
      potential importance of encouraging uxorilocal marriage in rural areas as a means
      of mitigating demographic and social problems related to son preference, such as
      high sex ratio at birth and lack of old-age security, which are projected for
      China's future.

PMID- 12194445
TI  - Are temporary migrants escapees of the one-child-per-family population policy: a
      revisit to the detachment hypothesis.
AB  - Using Hubei province as a case study, this paper retests the detachment
      hypothesis against the three conventional hypotheses regarding migration
      fertility linkage (i.e., selectivity, disruption, and adaptation hypotheses) in
      explaining migrant and non-migrant fertility differentials in China. The analysis
      of yearly order-specific birth probabilities suggests that temporary migrants
      exhibit a significantly higher probability of having a second or higher order
      birth than comparable permanent migrants and non-migrants. This higher fertility
      among temporary migrants occurs after migration; temporary migrants actually do
      not differ from non-migrants in fertility before migration. But permanent
      migrants experience no significant change in their fertility after migration. The
      results lend a strong support to the detachment hypothesis, which best explains
      the fertility differentials between migrant and non-migrant populations in
      contemporary China; the separation of temporary migrants' actual residence from
      their official one does lead to a greater likelihood among temporary migrants to
      have unplanned births.

PMID- 12194446
TI  - Menarcheal age and subsequent patterns of family formation.
AB  - We examine whether age at menarche affects age at first marriage or first birth
      using two samples of U.S. women. Data are drawn from the Tremin Trust, a
      longitudinal study of menstrual cycles that recruited white women who were
      students at the University of Minnesota and from a survey of a nationally
      representative sample of white women born between 1900 and 1910. Regression
      models with cubic splines were used to analyze the relationship between age at
      menarche and age at first marriage. Cox proportional hazard models were used to
      examine the effect of age at menarche on the interval between marriage and first
      birth. Unlike earlier work, we found that once secular trends in both age at
      marriage and age at menarche were taken into account, there was no evidence that
      age at menarche affects either age at marriage or the timing of first births in
      these U.S. women.

PMID- 12194447
TI  - Poverty, prenatal care, and infant health in Puerto Rico.
AB  - Using data from a survey administered to a representative sample of mothers who
      gave birth in Puerto Rico in 1994-95, we investigate whether prenatal care and
      infant health outcomes are associated with family poverty and neighborhood
      poverty. The results show that infant health outcomes are unrelated to both
      family poverty and neighborhood poverty, despite the association of family
      poverty with the adequacy of prenatal care and the content of prenatal care.
      However, the poverty paradigm does receive some support using measures of
      participation in government programs that serve the low-income population. Women
      who rely on the government to fund their medical care are more likely than women
      who rely on private health insurance to have an infant death. They are also less
      likely to receive the highest levels of prenatal care. Nonetheless, targeted
      government programs can have an ameliorative impact. The analysis shows that
      participants in the Women, Infants, and Children (WIC) program are more likely
      than non-participants to receive superior levels of prenatal care and are less
      likely to have negative infant health outcomes.

PMID- 12194448
TI  - Poverty, insurance, and well-baby care among mainland Puerto Rican children.
AB  - Using data from the Puerto Rican Maternal and Infant Health Study, we investigate
      the implications of family income and insurance status for well-baby care among
      mainland Puerto Ricans. Given the socioeconomic disadvantage of Puerto Ricans, it
      is critical to understand the extent to which low income and lack of health
      insurance create barriers to well-baby care and result in low utilization. The
      analysis shows that the income-to-needs ratio is related to barriers to well-baby
      care, and a key intervening factor is insurance status. The odds of reporting any
      barriers to care are lowest among those with both adequate income and private
      health insurance. Access to insurance is also vital in achieving adequate well
      baby care. Uninsured children receive inadequate care more often than children
      with public or private insurance, especially when their income is also low.
      Children with public insurance are as likely as children with private insurance
      to receive an adequate number of well-baby visits, despite the fact that their
      mothers report more barriers to care.

PMID- 12194449
TI  - Regional, temporal, and seasonal variations in births and deaths: the effects of
      famines.
AB  - A knowledge of the seasonal variation in births and deaths during normal years is
      important for analyses of the effects of wars, famines, epidemics or similar
      privations on these two variables. In studies of seasonality, multiple
      trigonometric regression models are more flexible than the simple sine curve. The
      seasonal variation in mortality in Iceland, 1856-1990, shows a strong secular
      decrease, and a connection between this and the epidemiological transition is
      considered. As a consequence of the severe famine in Finland in 1867-68, the
      mortality for the whole year 1868 was almost four times as high as during normal
      years, and the seasonality of the mortality was even more accentuated. The birth
      rate in Finland during 1868 was about 70 percent of that during normal years and
      showed an aberrant seasonality, with a strong trough from October 1868 to
      February 1869 (fewer conceptions between January and May 1868, when the food
      shortage was severe).

PMID- 12194450
TI  - Antibacterial activity in four marine crustacean decapods.
AB  - A search for antibacterial activity in different body-parts of Pandalus borealis
      (northern shrimp), Pagurus bernhardus (hermit crab), Hyas araneus (spider crab)
      and Paralithodes camtschatica (king crab) was conducted. Dried samples were
      extracted with 60% (v/v) acetonitrile, containing 0.1% (v/v) trifluoroacetic
      acid, and further extracted and concentrated on C18 cartridges. Eluates from the
      solid phase extraction were tested for antibacterial, lysozyme and haemolytic
      activity. Antibacterial activity against Escherichia coli, Vibrio anguillarum,
      Corynebacterium glutamicum and Staphylococcus aureus was detected in extracts
      from several tissues in all species tested, but mainly in the haemolymph and
      haemocyte extracts. V. anguillarum and C. glutamicum were generally the most
      sensitive micro-organisms. In P. borealis and P. bernhardus most of the active
      fractions were not affected by proteinase K treatment, while in H. araneus and P.
      camtschatica most fractions were sensitive to proteinase K treatment, indicating
      antibacterial factors of proteinaceous nature. In P. bernhardus the active
      fractions were generally heat labile, whereas in H. araneus the activities were
      resistant to heat. Differences between active extracts regarding hydrophobicity
      and sensitivity for heat and proteinase K treatment indicate that several
      compounds are responsible for the antibacterial activities detected. Lysozyme
      like activity could be detected in some fractions and haemolytic activity against
      human red blood cells could be detected in haemolymph/haemocyte and exoskeleton
      extracts from all species tested.

PMID- 12194452
TI  - The complement system in teleosts.
AB  - Complement, an important component of the innate immune system, is comprised of
      about 35 individual proteins. In mammals, activation of complement results in the
      generation of activated protein fragments that play a role in microbial killing,
      phagocytosis, inflammatory reactions, immune complex clearance, and antibody
      production. Fish appear to possess activation pathways similar to those in
      mammals, and the fish complement proteins identified thus far show many
      homologies to their mammalian counterparts. Because information about complement
      proteins, regulatory proteins, and complement receptors in fish is far from
      complete, it is unclear whether all the complement functions that have been
      identified in mammals also occur in fish. However, it has been clearly
      demonstrated that fish complement can lyse foreign cells and opsonise foreign
      organisms for destruction by phagocytes. There are also indications that
      complement fragments participate in inflammatory reactions. Fish possess multiple
      isoforms of several complement proteins, such as C3 and factor B. It has been
      hypothesised that the function of this diversity in complement proteins serves to
      expand their innate immune recognition capacity and response. Understanding the
      functions of complement in fish and the roles the individual proteins, including
      the various isoforms, play in host defence, is important not only for
      understanding the evolution of this system but also for the development of new
      strategies in fish health management.

PMID- 12194451
TI  - Type I-interferon signalling in fish.
AB  - Type I interferon (IFN) signalling uses a dual mechanism of action. A Jak-Stat
      pathway extensively described in mammals involves a cascade of reactions from the
      interaction of the IFN molecule with its membrane receptor to the stimulation of
      IFN-induced gene promoters leading in turn to an antiviral state. Regulation of
      IFN activity is also mediated by two DNA-binding transcription factors called
      interferon regulatory factor (IRF)-1 and -2, that respectively stimulate and
      repress the promoter of IFN-induced genes. By gene walking with trout genomic DNA
      the regulatory sequence of the IRF-1 gene was cloned and sequenced. Sequence
      analysis showed that this 1 Kb 5' flanking region has a structure which is
      typical for an IFN-induced gene promoter. It contains a TATA box between -28 to 
      31, and a NF kappa B site between -41 and -52. No complete interferon stimulatory
      response element (ISRE) could be found, but ten GAAA motifs, which are
      characteristic of IFN-induced gene promoters, were found. In rainbow trout gonad
      (RTG) cells, IRF-1 is expressed constitutively and up-regulated by poly I:C but
      not by LPS. Transient transfections of RTG cells with a reporter construct based
      on the luciferase gene show that the IRF1 5' flanking region described above, is
      sufficient to allow the expression of luciferase and is capable of induction by
      dsRNA (poly I:C).

PMID- 12194453
TI  - Early events in crustacean innate immunity.

PMID- 12194454
TI  - DNA vaccines as a tool for analysing the protective immune response against
      rhabdoviruses in rainbow trout.
AB  - DNA vaccines based on the glycoprotein genes of the salmonid rhabdoviruses VHSV
      and IHNV have been demonstrated to be very efficient in inducing a protective
      immune response against the respective diseases in rainbow trout. Nanogram doses
      of plasmid DNA delivered by intramuscular injection are sufficient to induce high
      levels of immunity in fingerling-size fish, whereas larger fish require more
      vaccine for protection. The protection is long lasting and, more surprisingly, is
      partly established already 4 days post vaccination. The early protection involves
      cross-protective anti-viral defence mechanisms, while the long duration immunity
      is highly specific. The nature of these immune response mechanisms is discussed
      and it is suggested that the efficacy of the vaccines is related to their ability
      to activate the innate immune system as it is activated by live virus.

PMID- 12194455
TI  - Social security entitlements, rehabilitation and therapeutic jurisprudence.

PMID- 12194457
TI  - Bioterrorism and biological warfare.

PMID- 12194456
TI  - Legal issues in reproductive rights.

PMID- 12194458
TI  - Anthrax.

PMID- 12194459
TI  - The New Zealand Health and Disability Commissioner: a comparative assessment of
      the commissioner's contribution to protecting the rights of mental health
      consumers.
AB  - The Health and Disabliity Commissioner's contribution to the protection of mental
      health consumers' rights is examined. This assessment covers a number of aspects.
      It includes the scope of consumer rights jurisdiction, the breadth of legal
      entitlements, protective mechanisms used, and the effectiveness of that
      protection. The Commissioner's role is also assessed comparatively. It is
      contrasted domestically with District Inspectors of Mental Health and
      internationally with Scottish and United Kingdom reform proposals. While analysis
      reveals considerable similarities, the New Zealand Health and Disability
      Commissioner is favourably highlighted in contrast with Scotland and the United
      Kingdom, particularly in the area of enforceability of mental health consumer
      rights.

PMID- 12194460
TI  - Litigation: a threat to obstetric practice?
AB  - Claims that the practice of obstetrics is in crisis appear regularly in the
      media, but evidence for the claims is scarce. This article examines a range of
      evidence from Australia and overseas and explores the relationship between
      obstetric practice and litigation. While anecdotal evidence abounds, there is no
      hard evidence to confirm that litigation is the threat to obstetric practice that
      many practitioners strongly believe it is. It is likely that such practitioners
      respond by practising defensive medicine but this is very difficult to measure.

PMID- 12194461
TI  - The search for truth and freedom: ethical issues surrounding human cloning and
      stem cell research.
AB  - The reality of cloning and stem cell research has provoked wonder, fear and
      anger. These developments have the potential fundamentally to alter humanity. But
      how well informed is the range of views being expressed? Is progress being
      threatened by understandable but uninformed fears? Or are scientists rushing
      toward an ethical abyss, so concerned with what they can do that they never stop
      to ask what they should do? This article identifies some of the fears and hopes
      surrounding cloning and stem cell research. It aims to provoke ethical debate in
      evaluating such research.

PMID- 12194462
TI  - State secrets: access to information under the Human Reproductive Technology Act
      1991 (WA).
AB  - Many Australian children have a biological father who gave his sperm so that the
      child's mother could conceive and raise them. Many of these children, and their
      parent(s), do not know who that biological father is. However, some want to know.
      The article examines the Western Australian law on access to information about
      the identity of parties in these arrangements. It is argued that there is an
      implied right to access identifying information where all parties consent to the
      exchange of information; that this right has been ignored in official and medical
      practice and opportunities for good record-keeping missed; and that the current
      law allows a parent to give consent to the exchange of identifying information on
      behalf of their child at any time after the child is conceived.

PMID- 12194463
TI  - Social science research and experimentation in Australian criminal proceedings:
      prejudicial pre-trial publicity and psychological research.
AB  - Using the decision of Barr J in Attorney-General (NSW) v John Fairfax
      Publications [1999] NSWSC 318, the authors analyse the need for external validity
      and relevance in social science evidence adduced in the courts. They argue in
      favour of the rigour employed within Barr J's judgment and contend that a
      constructive legacy of the decision should be a greater sensitisation on the part
      of researchers to the kinds of factors that can distance experimental scenarios
      from curial contexts to a point where generalisations from the former become
      strained and even spurious. A number of these considerations have the potential
      to be addressed to a significant extent by improved methodologies. However, the
      authors warn against an excess of purist fervour in demanding complete
      comparability of scenarios, lest the fruits of social science be denied to the
      courts and decision-making be adversely affected by the absence of expert
      insights falling short of complete replication of conditions between experiments
      and forensic reality.

PMID- 12194464
TI  - Regulating reproductive technologies.

PMID- 12194465
TI  - Regulating embryonic stem cell research in the United Kingdom.

PMID- 12194466
TI  - Regulating human embryo research in Australia: recent developments.

PMID- 12194467
TI  - Human cloning: a challenge for legislation.

PMID- 12194468
TI  - Aggression and assault against nurses in the workplace: practice and legal
      issues.

PMID- 12194469
TI  - Access to artificial insemination by donor--Women in lesbian relationship. Morgan
      v GK. [2001] QADT 10.

PMID- 12194470
TI  - Negligence--Failure to warn--Failure to provide adequate follow-up. Jaensch v
      Campbell. [2001] NTSC 87.

PMID- 12194471
TI  - Negligence--Failure to carry out physical examination and biopsy--Damages for
      loss of chance of extended lifespan. Brown v Willington. [2001] ACTSC 100.

PMID- 12194472
TI  - The art of regulation and the regulation of ART: the impact of regulation on
      research and clinical practice.
AB  - How a society regulates Assisted Reproduction Technologies (ART) depends on
      cultural context. The challenge for the regulatory regime is to balance
      protection for patients and society with freedom for medico-scientific
      creativity. Neither an exclusively market-regulated nor a peer-regulated approach
      is realistic politically, or desirable socially, ethically and legally.
      Legitimate social issues that go beyond the exclusive expertise of doctors and
      scientists or market choice by patients need to be accommodated within the
      regulatory regime. Within this context, four key issues are discussed: the lack
      of a shared social ethic that helps the needs of the community to be balanced
      against those of its individual members; the negative impact of intrusive
      external regulation on scientists and doctors; the requirement for doctors and
      scientists to review their professional structures reflectively and critically if
      they are to be entrusted with peer-regulation; and the desirability of
      constructive dialogue between regulators and regulated rather than the use of
      coercion and criminal sanctions.

PMID- 12194473
TI  - Professional self-regulation and guidelines in assisted reproduction.
AB  - Australia's scientific expertise in ART has not been matched by similar standards
      in national regulation. Scientific breakthroughs in the early 1980s were followed
      by cohorts of State and national inquiries. Early guidelines by the National
      Health and Medical Research Council were followed by status of children
      legislation clarifying their parentage where donated gametes were used. The
      practice and procedure of ART was legislatively regulated in Victoria, Western
      Australia and South Australia but left to guidelines and accreditation of the
      Fertility Society of Australia in the remaining States and Territories. The
      article examines the consequences of an absence of national regulation in dealing
      with embryo experimentation now that debates have shifted to human cloning and
      stem cell technology. The article also considers arguments for and against
      regulation in areas of parental procreative decision-making and embryo
      experimentation.

PMID- 12194474
TI  - Post-mortem human reproduction: legal and other regulatory issues.
AB  - Increasingly women are seeking to establish pregnancies using sperm retrieved
      from their dead or dying partners. This raises a number of issues of a broad
      nature, but is also of significance in terms of the relationship between
      regulatory mechanisms and private choices. This article reviews this relationship
      with specific reference to the United Kingdom position, but also taking account
      of case law and regulation in Australia, particularly in the State of Victoria.

PMID- 12194475
TI  - When transgressions become transparent: limiting family forms in assisted
      conception.
AB  - This article explores the social processes through which ideas about the family
      become translated into regulation and practice in assisted conception. Drawing on
      social problems literature, it is suggested that claims are made (by regulators,
      practitioners and others) about the desirability of certain family types and that
      forms of regulation occur when families transgress, in particularly obvious ways,
      the boundaries of those definitions. The apparently disparate examples of lesbian
      access to donor insemination and donor anonymity are brought together to
      illustrate the argument. It is also suggested that much formal regulation and
      clinical practice is directed towards making such transgressions less
      transparent, thus protecting the practice of assisted conception from unwelcome
      scrutiny.

PMID- 12194476
TI  - Families and future children: the role of rights and interests in determining
      ethical policy for regulating families.
AB  - "Rights" and "interests" are key ethical concepts in the debate on the regulation
      of Assisted Reproductive Technology. This article examines some of the ways in
      which these terms have been used in the debate, concentrating on their
      application to the situation of the potential children resulting from the
      technology. The article argues that, while there have been many misuses of these
      terms by the parties to the often acrimonious debate, nevertheless ethical
      regulation depends on maintaining the concepts as of central importance, but at
      the same time clarifying their use.

PMID- 12194477
TI  - Problems with the regulation of assisted reproductive technology: a clinician's
      perspective.
AB  - The use of the Infertility Treatment Act 1995 (Vic) as a model for regulating
      reproductive technologies throughout Australia poses many problems. This article
      argues that the legislation in Victoria is overly restrictive. In particular,
      banning embryo research is hypocritical. Embryo research was required to develop
      the clinical procedures and should be used to test innovations. Other problems
      are restricted access; privacy infringement; an intrusive regulatory body;
      conflicts with other laws; and confusion because of poor drafting or lack of
      foresight. Uniform statutes are unnecessary. The interests of individuals and the
      community are better served by regulation through the Reproductive Technology
      Accreditation Committee.

PMID- 12194478
TI  - The nanny state or responsible government?
AB  - The use of statutory regulation of medical treatments is always contentious. This
      is particularly so in the case of assisted reproductive technologies (ART), and
      the treatments offered through IVF and related procedures. These technologies
      challenge traditional understandings of the family and motherhood, but also raise
      questions about the status of the human embryo and how it should be treated. This
      article argues that governments do have a role to play in the regulation of ART,
      in addition to the professional guidelines governing such treatments. It looks at
      three different types of statutory regulation in the Australian context.

PMID- 12194479
TI  - The regulation of assisted reproductive technology: a comparative study of
      permissive and prescriptive laws and policies.
AB  - A specific statute governing assisted reproduction is one way to regulate
      assisted reproduction. However, what type of statute is best suited to an area of
      medicine that is subject to rapid technological advances and also affects human
      rights and interests? What are the strengths and weaknesses of a permissive model
      of regulation compared to a prescriptive model of regulation? This article
      examines the Human Fertilisation and Embryology Act 1990 (UK) and the Infertility
      Treatment Act 1995 (Vic) in the context of eligibility for infertility treatment
      and the roles played by the United Kingdom Human Fertilisation Embryology
      Authority and the Victorian Infertility Treatment Authority.

PMID- 12194480
TI  - Regulation, consultation and divergent community views: the case of access to ART
      by lesbian and single women.
AB  - In the many countries which have some form of regulation of ART, a public
      consultation of some sort is a frequent feature of either the process leading up
      to regulation or of the regulatory mechanism itself. Not surprisingly, widely
      divergent views on the moral and political acceptability of ART are expressed
      during such consultations. And while such diversity of opinion is to be expected,
      and some even argue welcomed, in pluralist liberal democratic societies, it is
      often unclear how these divergent community views are and ought to be fed into
      the opinion-forming and decision-making processes of governments or the bodies
      that advise them. This article discusses first why regulation of ART may be
      justified, even when there is radical moral disagreement in the community, and
      why public consultations should play a central role in the work that advisory
      bodies undertake in making regulatory recommendations to government. Then, it
      both proposes and justifies a method for dealing with the contradictory moral
      views expressed by interested parties during the consultation process. To
      illustrate this method, the example of the attempt by single and lesbian women to
      access donor insemination services and ART is used.

PMID- 12194481
TI  - Litigation: a threat to obstetric practice.

PMID- 12194482
TI  - Effect of pulp and paper mill effluent (BKME) on physiological parameters of
      roach (Rutilus rutilus) infected by the digenean Rhipidocotyle fennica.
AB  - Physiological parameters were measured after experimental infection of roach
      (Rutilus rutilus L.) with Rhipidocotyle fennica Gibson, Valtonen et Taskinen,
      1992 (Digenea) cercariae. The fish were caught from two lakes: a eutrophic
      bleached kraft mill effluent (BKME)-contaminated lake and an oligotrophic
      unpolluted lake. The intensity of infection was followed up to 10 days post
      infection (p.i.) and physiological parameters indicating non-specific stress
      responses and the condition of fish were examined simultaneously. The mean
      abundance, the number of parasites per fish, of R. fennica was significantly
      higher in the fish from the contaminated water during the first two days p.i.,
      probably reflecting the decreased resistance of these fish to infection. The
      decrease of leukocrit, as well as the increase of the activity of transaminases
      (GOT and GPT) in infected fish of both groups are suggestive of pathological
      processes caused by cercariae penetrating the fish. A significantly lower
      leukocrit value, as well as higher alkaline phosphatase activity and plasma
      chloride levels were noted in fish originating from the contaminated lake
      compared to those from the unpolluted lake. No significant differences were noted
      in haematocrit, plasma protein and calcium values between the fish from the
      uncontaminated and contaminated lakes, or between the infected and uninfected
      control fish.

PMID- 12194483
TI  - Two new nematodes, Paraseuratoides ophisterni gen. et sp. n. (Quimperiidae) and
      Philometra ophisterni sp. n. (Philometridae), from the swamp-eel Ophisternon
      aenigmaticum in Mexico.
AB  - Two new nematodes, Paraseuratoides ophisterni gen. et sp. n. (Seuratoidea:
      Quimperiidae) and Philometra ophisterni sp. n. (Dracunculoidea: Philometridae)
      are described based on specimens recovered from the intestine and mesentery,
      respectively, of the swamp-eel Ophisternon aenigmaticum Rosen et Greenwood
      (Synbranchiformes: Synbranchidae) from a canal of the Papaloapan River in
      Tlacotalpan, State of Veracruz, Mexico. The genus Paraseuratoides is mot similar
      to Paraseuratum Johnston et Mawson, 1940, differing from it mainly in the absence
      of a bulbous inflation on the anterior end of the oesophagus and in the structure
      of the mouth (presence of 6 spines in addition to 6 oesophageal teeth).
      Neoquimperia Wang, Zhao, Wang et Zhang, 1979 and Wuinema Yu et Wang, 1992 are
      synonymised with Ezonema Boyce, 1971 and Paragendria Baylis, 1939, respectively,
      and Haplonema hamulatum Moulton, 1931 is considered a junior synonym of
      Ichthyobronema conoura Gnedina et Savina, 1930. Philometra ophisterni (only
      females) is mainly characterised by minute cephalic papillae, a greatly developed
      anterior oesophageal bulb separated from the cylindrical part of the oesophagus,
      anterior extension of the oesophageal gland anterior to the nerve ring, and by
      the character of large caudal projections. This is the first Philometra species
      recorded from inland fishes in Mexico.

PMID- 12194485
TI  - Post-cyclic transmission in Acanthocephalus tumescens (Acanthocephala:
      Echinorhynchidae).
AB  - The aim of this study was to investigate the post-cyclic transmission of
      Acanthocephalus tumescens (von Linstow, 1896) from Galaxias maculatus Jenyns to
      Oncorhynchus mykiss (Walbaum). Wild G. maculatus naturally infected with A.
      tumescens were fed to cultured rainbow trout, which were sacrificed at the
      second, third and fourth weeks post infection. Normally attached male and female
      acanthocephalans were recovered alive from the intestine of rainbow trout.
      Parasites survive at least four weeks post infection, growing and attaining full
      sexual maturity. Prevalence and mean intensity generally decreased after
      infection. A. tumescens is the eighth acanthocephalan species in which post
      cyclic transmission has been proven.

PMID- 12194484
TI  - Development of Spinitectus inermis (Nematoda: Cystidicolidae), a parasite of eel,
      Anguilla anguilla, in Europe.
AB  - The development of the nematode Spinitectus inermis (Zeder, 1800), a parasite of
      the stomach of eels, Anguilla anguilla (L.) in Europe, was experimentally
      studied. Mayfly nymphs Caenis macrura, Ecdyonurus dispar, Heptagenia sulphurea,
      Potamanthus luteus and Seratella ignita from Portugal and the Czech Republic were
      found to serve as experimental intermediate hosts. After ingestion of the
      nematode eggs by the mayfly nymphs, the toothed first-stage larvae were released
      and penetrated into the body cavity of the intermediate host. There they moulted
      twice (on day 4 and 6 post infection [p.i.] at water temperatures of 20-25
      degrees C), attaining the third infective stage. The definitive host, A.
      anguilla, undoubtedly acquires infection by feeding on mayfly nymphs harbouring
      infective-stage larvae. In an experimentally infected eel, the fourth-stage larva
      undergoing the third moult was observed 28 days p.i. at water temperature of 20
      degrees C. The larval stages, including moulting forms, are described and
      illustrated. The prepatent period of S. inermis is estimated to be about two
      months.

PMID- 12194486
TI  - Description of the previously unknown male of Caligus mortis Kensley, 1970
      (Copepoda: Caligidae), parasite of intertidal fish from South Africa.
AB  - Caligus mortis Kensley, 1970 was originally described from females collected from
      intertidal pools along the coast of Namibia. During surveys at Jeffreys Bay and
      De Hoop Nature Reserve in South Africa, both females and males of C. mortis were
      collected from intertidal pool fish hosts. Based on this material a full
      description of the male is given, and a comparison with the female reveals the
      sexual dimorphic characteristics.

PMID- 12194487
TI  - Gnathia pantherina sp. n. (Crustacea: Isopoda: Gnathiidae), a temporary
      ectoparasite of some elasmobranch species from southern Africa.
AB  - Haematophagous larvae of a gnathiid isopod were collected from the gills, nares
      and buccal cavity of a single leopard catshark Poroderma pantherinum (Smith,
      1838) at Jeffreys Bay and five puffadder shysharks Haploblepharus edwardsii
      (Voight, 1832) and one blackspotted electric ray Torpedo fuscomaculata Peters,
      1855, at the De Hoop Nature Reserve on the South African south coast. Larvae were
      kept in fresh seawater until their moult into adult stages. The morphology of the
      adult males did not conform to that of any known species and they are therefore
      described as Gnathia pantherina sp. n. The descriptions of the adult male, female
      and praniza larva are based on light and scanning electron microscopy
      observations. Characteristic features of this species include the large size of
      all the final life-cycle stages, the deeply divided mediofrontal process of the
      male, the morphology of the pylopods and maxillipedes of the female, and the
      number of teeth on the mandibles (eight) and maxillules (seven) of the praniza
      larvae.

PMID- 12194488
TI  - Tick salivary gland extract-activated transmission of Borrelia afzelii
      spirochaetes.
AB  - Saliva-activated transmission of Borrelia afzelii Canica, Nato, du Merle, Mazie,
      Baranton et Postic, 1993 was demonstrated using salivary gland extract (SGE) from
      Ixodes ricinus (L., 1758) ticks and C3H mice. Injection of Borrelia spirochaetes
      together with SGE increased the level of bacteraemia and accelerated the
      appearance of bacteria in the urinary bladder, compared with the injection of
      spirochaetes alone. More I. ricinus nymphs became infected when feeding on mice
      inoculated with B. afzelii plus SGE. Analysis of cytokines produced by cells of
      draining lymph nodes from SGE-treated mice showed a suppression of
      proinflammatory cytokines IFN-gamma, IL-6 and GM-CSF following a transient
      upregulation in comparison with the control mice infected without SGE.

PMID- 12194491
TI  - Ultrastructure of pigmented photoreceptor of adult Crepidostomum metoecus
      (Trematoda: Digenea: Bunoderidae).

PMID- 12194489
TI  - Spirorbid [correction of Spirorchid] and serpulid polychaetes are candidates as
      invertebrate hosts for myxozoa.

PMID- 12194490
TI  - House fly (Musca domestica) as a transport vector of Cryptosporidium parvum.

PMID- 12194492
TI  - Observations on the occurrence and maturation of Spinitectus inermis (Nematoda:
      Cystidicolidae) in the Sousa River, Portugal.

PMID- 12194493
TI  - Myxobolus species (Myxozoa), parasites of fishes in the Okavango River and Delta,
      Botswana, including descriptions of two new species.
AB  - Fieldwork was conducted in 1998 and 1999 in the Okavango River and Delta and a
      total of 275 fishes representing 31 species were examined for the presence of
      myxosporean parasites. A total of seven myxosporeans of the genus Myxobolus
      Butschli, 1882 were found infecting the fishes. Two new species namely Myxobolus
      etsatsaensis sp. n. from Barbus thamalakanensis Fowler, 1935 and M. paludinosus
      sp. n. from Barbus paludinosus Peters, 1852 are described. Myxobolus africanus
      Fomena, Bouix et Birgi, 1985, M. camerounensis Fomena, Marques et Bouix, 1993, M.
      hydrocyni Kostoingue et Toguebaye, 1994, M. nyongana (Fomena, Bouix et Birgi,
      1985) and M. tilapiae Abolarin, 1974 are recorded for the first time in Botswana
      and descriptions of these species are provided.

PMID- 12194494
TI  - A new form of raabeia-type actinosporean (Myxozoa) from the oligochaete Uncinais
      uncinata.
AB  - In a study of the oligochaete fauna and their actinosporean parasites in three
      lakes in Algonquin Park, Canada, a novel form of raabeia-type actinosporean was
      observed in a single specimen of Uncinais uncinata (Oersted) (Naididae). This
      form differs from those previously described in its small size, and by having
      caudal processes that gradually widen and terminate with a single prominent
      branch.

PMID- 12194495
TI  - Haploporus mugilis sp. n. (Digenea: Haploporidae) from Valamugil engeli (Pisces:
      Mugilidae) in the Taiwan Straits, China.
AB  - Haploporus mugilis sp. n. (Digenea: Haploporidae) was obtained from the intestine
      of kandas, Valamugil engeli (Bleeker) (Mugilidae, Perciformes) in the Taiwan
      Straits, China. It most closely resembles Haploporus spinosus Machida, 1996 from
      the intestine of Crenimugil crenilabis in Japanese and adjacent waters in the
      intestinal bifurcation posterior to the acetabulum, in egg-size (0.039-0.044 x
      0.019-0.022 in H. mugilis and 0.034-0.042 x 0.018-0.023 in H. spinosus) and in
      the hermaphroditic sac armed with spines. However, it differs from the latter in
      its hermaphroditic sac with two long and numerous small spines rather than with
      four long and six small spines and in the excretory vesicle with a single
      prominent refractory concretion instead of being empty.

PMID- 12194496
TI  - Morphological features of Prosorhynchus crucibulum and P. aculeatus (Digenea:
      Bucephalidae), intestinal parasites of Conger conger (Pisces: Congridae),
      elucidated by scanning electron microscopy.
AB  - The external morphology of two bucephalid digenean parasites of Conger conger
      (Linnaeus) (Congridae, Anguilliformes) caught northwest of the Iberian Peninsula,
      Prosorhynchus crucibulum (Rudolphi, 1819) Odhner, 1905 and P. aculeatus Odhner,
      1905, were studied using scanning electron microscopy (SEM). SEM techniques
      elucidated new external morphological details, mainly relating to the tegument
      and protruding organs, such as, in P. crucibulum, a papilla-like structure
      associated with the pharynx and, in P. aculeatus, the cirrus. The tegument bears
      scale-like spines, which in both species are arranged quincuncially. The spines
      of P. crucibulum are wider than long and cover the major part of the body and
      rhynchus. However, no spines were found in either the central apical depression
      of the rhynchus or in the middle of the ventral indentation. Also, spines were
      rarely seen on the tegument around mouth, around the genital aperture or close to
      the excretory pore. P. aculeatus has spines of a different shape, as wide as they
      are long and with a rounded margin. They cover the whole body and almost the
      entire rhynchus, but none were found in the middle of the rhynchus or on its neck
      region.

PMID- 12194497
TI  - Calcium dysregulation in the aging brain.
AB  - The idea that age-related cognitive decline is associated with disruption of
      calcium (Ca2+) homeostasis has been investigated over the past two decades. Much
      of this work has focused on the hippocampus because hippocampal-dependent memory
      is age sensitive. It is now well established that Ca(2+)-dependent processes such
      as susceptibility to neurotoxicity, the afterhyperpolarization amplitude,
      induction of synaptic plasticity, and long-term potentiation and long-term
      depression are altered with age. Recent work has identified changes in Ca2+
      signaling pathways that may underlie the development of these biological markers
      of aging. This review considers recent findings concerning interactions between
      the various Ca(2+)-dependent processes, with special emphasis on the role of
      altered Ca2+ regulation and disruption of Ca2+ signaling pathways in mediating
      the expression of biological and behavioral markers of brain aging.

PMID- 12194499
TI  - Cortex governs multisensory integration in the midbrain.
AB  - Neurons in the superior colliculus (SC), a prominent midbrain structure, are able
      to synthesize information from different senses. This synthesis plays an
      important role in determining whether SC-mediated orientation behaviors will be
      initiated. In some circumstances, multisensory integration in the SC is evident
      as a response that is significantly enhanced above that evoked by the most
      effective single-modality stimulus. It can sometimes even exceed the arithmetic
      sum of the single-modality responses. In other circumstances, multisensory
      integration is evident as response depression, an effect sometimes powerful
      enough to eliminate even robust single-modality responses. The conditions that
      produce multisensory enhancement also increase the probability of orientation
      responses, and those that produce multisensory response depression decrease the
      probability of orientation responses. Although one might posit that the
      capability to integrate cross-modal cues (and, in this case, alter overt
      behavior) would be evident in all neurons capable of responding to stimuli from
      two or more sensory modalities, this turns out to be incorrect. When descending
      influences from the cortex are temporarily inactivated, SC neurons are rendered
      unable to synthesize their multiple sensory inputs, and animals no longer show
      enhanced orientation responses. Nevertheless, the ability to respond to cues from
      multiple sensory modalities is retained at both the single neuron and behavioral
      levels. Two cortical areas have been implicated in controlling these midbrain
      processes: the anterior ectosylvian sulcus and the rostral lateral suprasylvian
      sulcus.

PMID- 12194498
TI  - The thalamic reticular nucleus: more than a sensory nucleus?
AB  - Sensory information is routed to the cortex via the thalamus, but despite this
      sensory bombardment, animals must attend selectively to stimuli that signal
      danger or opportunity. Sensory input must be filtered, allowing only behaviorally
      relevant information to capture limited attentional resources. Located between
      the thalamus and cortex is a thin lamina of neurons called the thalamic reticular
      nucleus (Rt). The thalamic reticular nucleus projects exclusively to thalamus,
      thus forming an essential component of the circuitry mediating sensory
      transmission. This article presents evidence supporting a role for Rt beyond the
      mere relay of sensory information. Rather than operating as a component of the
      sensory relay, the authors suggest that Rt represents an inhibitory interface or
      "attentional gate," which regulates the flow of information between the thalamus
      and cortex. Recent findings have also implicated Rt in higher cognitive
      functions, including learning, memory, and spatial cognition. Drawing from recent
      insights into the dynamic nature of the thalamic relay in awake, behaving
      animals, the authors present a speculative account of how Rt might regulate
      thalamocortical transmission and ultimately the contents of consciousness.

PMID- 12194500
TI  - Dynamics of extracellular dopamine in the acute and chronic actions of cocaine.
AB  - Cocaine amplifies dopaminergic neurotransmission via blockade of presynaptic
      neuronal uptake. This action is believed to be a crucial component of cocaine's
      ability to exert its reinforcing effects. This review will provide a brief
      overview of extracellular dopamine dynamics associated with cocaine. The acute
      effects of cocaine reviewed include comparison of intravenous and intraperitoneal
      routes of administration to better understand how fast and slow routes (e.g.,
      crack and intranasal) differ in their pharmacokinetics and neurochemical effects
      and how those differences relate to differences in abuse potential. Changes in
      the acute effects of cocaine within a session have been examined in neurochemical
      studies of acute tolerance to self-administered cocaine in rhesus monkeys, and
      the potential impact of that tolerance to patterns of use is discussed. Between
      session sensitization of the dopaminergic response to cocaine is reviewed, and
      data indicating this also occurs in primates have been obtained in self
      administering rhesus monkeys, demonstrating neurochemical sensitization in a
      primate species. The important question of whether cocaine-associated
      environmental cues elicit conditioned increases in dopamine release has also been
      examined in the rhesus monkey, with results indicating that, unlike rats,
      nonhuman primates do not show conditioned increases in dopamine release.

PMID- 12194501
TI  - Role of superoxide dismutases in oxidative damage and neurodegenerative
      disorders.
AB  - In recent years, oxidative stress has been implicated in a variety of
      degenerative processes, diseases, and syndromes. Some of these include
      atherosclerosis, myocardial infarction, stroke, and ischemia/reperfusion injury;
      chronic and acute inflammatory conditions such as wound healing; central nervous
      system disorders such as forms of familial amyotrophic lateral sclerosis (ALS)
      and glutathione peroxidase-linked adolescent seizures; Parkinson's disease and
      Alzheimer's dementia; and a variety of other age-related disorders. Among the
      various biochemical events associated with these conditions, emerging evidence
      suggests the formation of superoxide anion and expression/activity of its
      endogenous scavenger, superoxide dismutase (SOD), as a common denominator. This
      review summarizes the function of SOD under normal physiological conditions as
      well as its role in the cellular and molecular mechanisms underlying oxidative
      tissue damage and neurological abnormalities. Experimental evidence from
      laboratory animals that either overexpress (transgenics) or are deficient
      (knockouts) in antioxidant enzyme/protein levels and the genetic SOD mutations
      observed in some familial cases of ALS are also discussed.

PMID- 12194502
TI  - Two phylogenetic specializations in the human brain.
AB  - In this study, two anatomical specializations of the brain in apes and humans are
      considered. One of these is a whole cortical area located in the frontal polar
      cortex (Brodmann's area 10), and the other is a morphologically distinctive cell
      type, the spindle neuron of the anterior cingulate cortex. The authors suggest
      that the spindle cells may relay to other parts of the brain--especially to area
      10, the outcome of processing within the anterior cingulate cortex. This relay
      conveys the motivation to act. It particularly concerns the recognition of having
      committed an error that leads to the initiation of adaptive responses to these
      adverse events so as to reduce error commission. This capacity is related to the
      development of self-control as an individual matures and gains social insight.
      Although the anterior cingulate deals with the individual's immediate response to
      changing conditions, area 10 is involved in the retrieval of memories from the
      individual's past experience and the capacity to plan adaptive responses. The
      authors suggest that these neurobehavioral specializations are crucial aspects of
      intelligence as defined as the capacity to make adaptive responses to changing
      conditions. The authors further hypothesize that these specializations
      facilitated the evolution of the unique capacity for the intergenerational
      transfer of the food and information characteristic of human extended families.

PMID- 12194503
TI  - Arrestin: roles in the life and death of retinal neurons.
AB  - G protein-coupled receptors are a large family of signaling molecules that
      respond to a wide variety of extracellular stimuli. The receptors relay the
      information encoded by the ligand through the activation of heterotrimeric G
      proteins and intracellular effector molecules. To ensure the appropriate
      regulation of the signaling cascade, it is vital to properly inactivate the
      receptor. This inactivation is achieved, in part, by the binding of a soluble
      protein, arrestin, which uncouples the receptor from the downstream G protein. In
      addition to the inactivation of G protein-coupled receptors, arrestins have also
      been implicated in the endocytosis of receptors and cross talk with other
      signaling pathways. Due to its central role in cellular signaling, misregulation
      or misfunction of arrestin can have dramatic affects on cell viability and have
      direct implications in human disease.

PMID- 12194505
TI  - Brain specialization for music.
AB  - Music, like language, is a universal and specific trait to humans. Similarly,
      music appreciation, like language comprehension, appears to be the product of a
      dedicated brain organization. Support for the existence of music-specific neural
      networks is found in various pathological conditions that isolate musical
      abilities from the rest of the cognitive system. Cerebrovascular accidents,
      traumatic brain damage, and congenital brain anomalies can lead to selective
      disorders of music processing. Conversely, autism and epilepsy can reveal the
      autonomous functioning and the selectivity, respectively, of the neural networks
      that subserve music. However, brain specialization for music should not be
      equated with the presence of a singular "musical center" in the brain. Rather,
      multiple interconnected neural networks are engaged, of which some may capture
      the essence of brain specialization for music. The encoding of pitch along
      musical scales is likely such an essential component. The implications of the
      existence of such special-purpose cortical processes are that the human brain
      might be hardwired for music.

PMID- 12194504
TI  - Cortical dysgenesis and epilepsy.
AB  - Cortical dysgenesis (CD) describes a wide spectrum of brain anomalies that
      involve abnormal development of the cerebral cortex. There is a strong
      association between CD and epilepsy, and it comprises a significant proportion of
      children and adults whose epilepsy cannot be controlled with medications. There
      has been intense effort to define the relationship between CD and epilepsy so
      that more effective therapies can be devised. These efforts have ranged from
      detailed study of people with CD and epilepsy from a clinical standpoint to
      single-cell analysis of mRNA expression and postsynaptic receptor function.
      Animal models have also been developed to mimic certain aspects of CD in a
      situation when quantitative, controlled, and interventional experiments can be
      performed that would not be possible in a clinical setting. This review will give
      an overview of human CD syndromes and their causes, when possible, and describe
      some specific abnormalities in dysplastic cortex that may underlie its
      epileptogenic potential. It will also review several animal models of CD that
      have been studied mechanistically from the standpoint of epileptogenesis. In
      conclusion, some general trends will be proposed based on human and animal
      studies to encapsulate our current understanding of CD and how it causes
      epilepsy.

PMID- 12194506
TI  - Hantavirus pulmonary syndrome--United States: updated recommendations for risk
      reduction. Centers for Disease Control and Prevention.
AB  - This report provides updated recommendations for prevention and control of
      hantavirus infections associated with rodents in the United States. It supersedes
      the previous report (CDC. Hantavirus infection--southwestern United States:
      interim recommendations for risk reduction. MMWR 1993; 42[No. RR-11]: 1-13).
      These recommendations are based on principles of rodent and infection control,
      and accumulating evidence that most infections result from exposure, in closed
      spaces, to active infestations of infected rodents. The recommendations contain
      updated specific measures and precautions for limiting household, recreational,
      and occupational exposure to rodents, eliminating rodent infestations, rodent
      proofing human dwellings, cleaning up rodent-contaminated areas and dead rodents,
      and working in homes of persons with confirmed hantavirus infection or buildings
      with heavy rodent infestations.

PMID- 12194507
TI  - Severe aplastic anemia associated with hepatitis and complicated by pulmonary
      aspergillosis: response to immune suppression and antifungal therapy.
AB  - The true etiology of severe aplastic anemia is unknown; however, autoimmune
      activation of T-lymphocytes is one of the potential causes. Stem cell
      transplantation is regarded as a first line therapy if a fully matched sibling is
      available. Immunosuppressive therapy is reserved for those who have no matched
      sibling available for transplant, or for those individuals who fall outside the
      age range eligible for stem cell transplantation. This case describes a child
      with a hepatitis-associated severe aplastic anemia for whom a fully matched
      sibling was available but a transplant was postponed due to active hepatitis.
      While awaiting bone marrow transplantation, the child acquired a life-threatening
      aspergillosis infection treated with amphotericin B, granulocyte infusions, and
      surgical resection of the involved lung. A decision was made to proceed with
      immunosuppressive therapy while waiting for successful treatment of the fungal
      infection. Following administration of equine anti-thymocyte globulin (ATG), high
      dose granulocyte colony stimulating factor (G-CSF), cyclosporine, and steroids,
      the child had partial hematopoietic reconstitution and is now followed in our
      clinic. This case demonstrates the extraordinary multidisciplinary care required
      during the early phases of treating severe aplastic anemia. With such care,
      recovery is a possibility.

PMID- 12194508
TI  - Loose lips sink ships.

PMID- 12194509
TI  - Reproducibility of gait analysis variables: one-step versus three-step method of
      data acquisition.
AB  - The purpose of the study was to evaluate the preciseness and repeatability of
      EMED-SF platform data collection using two different protocols. Gait variables of
      five healthy women and five men, with an average age of 27.3 +/- 3.2 years,
      weighing 67.5 +/- 13.3 kg, were evaluated. With a one-step and a three-step
      approach of data collection, peak pressure, pressure-time integral, and contact
      time were measured. Peak pressures were not significantly different between both
      methods. Significant differences were found between both methods in total contact
      time and pressure-time integral. Both methods were comparable in peak pressures
      (error between methods = 7.0), while the one-step protocol was more repeatable
      (intraclass correlation coefficient = 0.59) than the three-step protocol
      (intraclass correlation coefficient = 0.36). The error between methods for total
      contact time and pressure-time integral were 143.3 and 50.1, respectively,
      suggesting that the two protocols lead to different results. The one-step
      protocol (intraclass correlation coefficient = 0.40) had a higher repeatability
      than the three-step protocol (intraclass correlation coefficient = 0.31). The one
      step protocol has some advantages over the three-step protocol as far as
      repeatability, simplicity, convenience, and time conservation are concerned. For
      measuring total contact time and pressure-time integrals, both methods have
      comparable repeatability, although the protocols lead to different outcomes.

PMID- 12194510
TI  - Large displacement distal chevron osteotomy for the correction of hallux valgus
      deformity.
AB  - In order to assess outcomes and complications, a retrospective study of 38
      bunionectomy cases with large displacement distal chevron osteotomy (greater than
      or equal to 40% lateral translation) for hallux valgus was performed. Follow-up
      ranged from 12 to 130 months (average, 31 months). Subjective analysis consisting
      of the American Orthopedic Foot and Ankle Society (AOFAS) hallux
      metatarsophalangeal-interphalangeal scale was performed. Preoperative and
      postoperative radiographic intermetatarsal (IM) angles and hallux abductus angles
      were measured and compared. The average postoperative AOFAS score was 93.5. The
      average preoperative IM angle was 15.03 degrees (range 8 degrees-24 degrees) and
      the average postoperative IM angle was 4.84 degrees (range, -1 degree-11
      degrees). The average preoperative hallux abductus angle was 29.39 degrees
      (range, 16 degrees-53 degrees) compared to the average postoperative hallux
      abductus angle of 11.39 degrees (range, 2 degrees-28 degrees). It was found that
      an average lateral translation of 9.8 mm was able to achieve a relative change of
      the IM angle of 10 degrees. Evidence is presented that supports the fact that
      large displacement distal chevron osteotomies can be safely performed for the
      correction of metatarsus primus varus greater than 15 degrees associated with
      hallux valgus.

PMID- 12194511
TI  - A retrospective study of standing gastrocnemius-soleus stretching versus night
      splinting in the treatment of plantar fasciitis.
AB  - Plantar fasciitis is the most common cause of heel pain, yet the conservative
      treatment of plantar fasciitis is not standardized. This open retrospective study
      compared the effects of standing gastrocnemius-soleus stretching to a
      prefabricated night splint. One hundred and sixty patients with unilateral or
      bilateral plantar fasciitis were evaluated and treated according to the standard
      regimen in addition to either night splints or stretching. Seventy-one patients
      performed standing stretching of the gastrocnemius-soleus complex. Eighty-nine
      patients utilized the prefabricated night splint without standing stretching. The
      night splint treatment group had a significantly shorter recovery time (p <
      .001), fewer follow-up visits to recovery (p < .001), and fewer total additional
      interventions (p = .034) compared to the stretching group. Absolute body weight,
      body mass index, and age did not have a statistically significant effect on the
      time to recovery or additional interventions needed. The duration of pain prior
      to this treatment was a predictive factor and was associated with increased time
      to recovery and increased number of treatment interventions. Its was concluded
      that early treatment in a standardized four-tiered treatment approach, including
      the night splint without standing stretching of the gastrocnemius-soleus complex,
      speeds time to recovery.

PMID- 12194512
TI  - Optimal waiting period for foot salvage surgery following limb revascularization.
AB  - It is not clear how soon after bypass surgery tissue perfusion in the ischemic
      foot is adequate for healing. The purpose of this study was to determine the time
      interval for tissue to receive adequate oxygenation for healing following limb
      revascularization. Eleven patients with severe foot ischemia as defined by a
      transcutaneous oxygen tension (TcPO2) of 30 mm Hg or less were included in the
      study. TcPO2 measurements were performed prior to the lower extremity bypass and
      at postoperative day 1, 2, and 3. The mean preoperative value (9.27 mm Hg) was
      compared with the mean value at postoperative day 1 (17.73 mm Hg), postoperative
      day 2 (20.36 mm Hg), and postoperative day 3 (36.82 mm Hg) using paired samples t
      tests. Statistically significant differences were observed between the mean
      preoperative TcPO2 measurement and the mean TcPO2 measurement taken on the 3rd
      postoperative day. The mean TcPO2 level increased from 9.27 mm Hg preoperatively
      to 36.82 mm Hg by the 3rd postoperative day (p = .001). There was also a
      statistically significant difference between the mean values on the 2nd (20.36 mm
      Hg) and 3rd postoperative day (36.82 mm Hg) (p = .002). Despite this finding, 5
      of the 11 patients still had individual TcPO2 readings of less than 30 mm Hg on
      the 3rd postoperative day. Therefore, it can be concluded that in most instances
      tissue oxygenation reaches an adequate level after waiting at least 3 days
      following a bypass. Waiting 3 or more days could give adequate time for tissue
      reperfusion to promote healing of the surgical site.

PMID- 12194513
TI  - Blood flow changes in diabetic foot ulcers treated with dermal replacement
      therapy.
AB  - The study investigated whether the effects of dermal replacement therapy on wound
      healing are associated with an increase in blood flow at the base of diabetic
      foot ulcers treated with Dermagraft. Seven full-thickness ulcers were assessed in
      five patients with type 2 diabetes mellitus and peripheral neuropathy. All
      lesions had been present for at least 3 months with no recent change in size,
      despite routine foot care and protective dressings. Dermal replacement therapy
      was applied weekly to the base of each wound for 8 weeks, after which regular
      dressing was resumed. Microvascular blood flow was assessed using laser Doppler
      imaging immediately before and after 2, 5, and 8 weeks of treatment. Blood flow
      increased by an average of 72% in the base of five out of the seven ulcers
      studied. Five of the lesions healed by 12 weeks and the other two reduced in size
      by approximately 25%. The changes in blood flow observed in this pilot study
      might reflect angiogenesis in the newly formed granulation tissue and/or
      vasodilatation of existing vessels, processes that are possibly enhanced by the
      intervention.

PMID- 12194514
TI  - Treatment of an aneurysmal bone cyst of the second metatarsal using an endoscopic
      approach.
AB  - An aneurysmal bone cyst is a benign solitary lesion of unknown etiology. A case
      report is presented of recurrence of an aneurysmal bone cyst in the foot that was
      treated with endoscopic curettage without bone grafting. Bone remodeling and bone
      formation were completed in the early stages postsurgically. At 2-year follow-up,
      the patient is asymptomatic with no radiographic evidence of recurrence.

PMID- 12194516
TI  - Use of a reverse-flow plantar marginal septum cutaneous island flap for repair of
      a forefoot defect.
AB  - Soft-tissue reconstruction of the foot frequently requires flap coverage to
      preserve exposed tissues such as bones, joints, tendons, and weight bearing
      areas. Recently, reconstruction of skin defects in the heel has been greatly
      improved by use of the medial plantar sensory flap. However, forefoot coverage
      remains a challenge, since the alternatives for flap coverage are very limited. A
      case report is presented of a 52-year-old man with a chronic forefoot ulcer,
      successfully covered with a plantar marginal septum cutaneous island flap. This
      recently reported technique, which utilizes a reversed-flow flap based on the
      superficial branch of the medial division of the medial plantar artery, is
      relatively easy and disadvantages to the donor site are minimal.

PMID- 12194515
TI  - Acute tarsal tunnel syndrome following partial avulsion of the flexor hallucis
      longus muscle: a case report.
AB  - An acute posterior tibial nerve compression from a partially ruptured flexor
      hallucis longus (FHL) muscle is reported. This etiology for acute tarsal tunnel
      syndrome has not been previously described. A 17-year-old male sustained multiple
      injuries in a motor vehicle accident, including a tibial shaft fracture and a
      posterior medial right ankle laceration of the same limb. The injured limb had no
      sensation on the plantar aspect of the foot and heel, decreased active great toe
      flexion, and associated leg pain. Exploration of the posterior tibial nerve for
      presumed laceration revealed the nerve to be intact, but compressed in a tense
      tarsal tunnel from a retracted partially ruptured flexor hallucis longus tendon.
      Decompression of the tunnel and resection of the devascularized muscle resulted
      in complete neurologic recovery.

PMID- 12194517
TI  - Critiquing clinical research of new technologies for diabetic foot wound
      management.
AB  - Healing the diabetic foot ulcer has been a challenge. Over the past 20 years,
      researchers have gained significant knowledge about the biochemical mechanisms
      that underlie the process of wound repair. A literature review of the latest
      advanced technologies, devices, and therapies is provided. In addition, clinical
      decision-making insights for clinicians to evaluate research and to assist in
      choosing the correct modality for each of their diabetic foot ulcer patients are
      discussed.

PMID- 12194518
TI  - First metatarsocuneiform arthrodesis: technical considerations and technique
      modification.
AB  - Triplane malalignment of the first ray is frequently associated with instability
      and suboptimal spatial positioning at the first metatarsocuneiform joint (MCJ).
      The first metatarsocuneiform arthrodesis provides an effective means of
      addressing hypermobility in association with multiplanar first metatarsal
      malalignment. The first MCJ has a characteristic concave-convex surface
      topography that can allow the first metatarsal to translate within the transverse
      and sagittal planes. A method of "anatomical arthrodesis" of the first MCJ is
      described that utilizes the joint's unique topography to assist in the process of
      repositioning the first metatarsal. A step-by-step description of the procedure
      is provided with emphasis placed on identifying and highlighting unique areas of
      difficulty.

PMID- 12194519
TI  - Bone repair in radii and tibias of rabbits with phosphorylated chitosan
      reinforced calcium phosphate cements.
AB  - Biocompatibility of two calcium phosphate cements (CPCs), reinforced with
      phosphorylated chitosan (P-chitosan), was investigated in rabbits in present
      study. The two CPCs are monocalcium phosphate monohydrate (MPCM) with calcium
      oxide (CaO) in 1 M phosphate buffer (i.e. MCPM/CaO/1 M phosphate buffer cement,
      CPC-I) and dicalcium phosphate dihydrate (DCPD) with calcium hydroxide [Ca(OH)2]
      in 1 M Na2HPO4 solution (i.e. DCPD/Ca(OH)2/1 M Na2HPO4 cement, CPC-II). Different
      amount of P-chitosan was added to the liquid phase before the power phase was
      mixed with the liquid phase. The MCPM/CaO/1 M phosphate buffer/P-chitosan cements
      (P-CPC-I) with neutral pH were filled into the holey defects of rabbit tibias.
      While the DCPD/Ca(OH)2/1 M Na2HPO4/P-chitosan cements (P-CPC-II) shaped as
      prehardened cylinders were implanted into rabbit radial defects. After operation,
      the two serial groups and CPC-II controls were observed for 1, 4, 12 and 22
      weeks, respectively. Histological and histomorphological studies proved that P
      chitosan containing cements are biocompatible, bioabsorbable and osteoinductive.
      The biodegradation rate has a negative relationship with the P-chitosan content.
      Progressive substitution took place at the interface of implants and host bones.
      No adverse effects were found in tissues around the bone defects. Thus, they
      could be used as bone substitutes in clinic.

PMID- 12194520
TI  - In vitro and in vivo evaluation of alginate/sol-gel synthesized aminopropyl
      silicate/alginate membrane for bioartificial pancreas.
AB  - Alginate/aminopropyl-silicate/alginate (Alg/AS/Alg) membrane was prepared on Ca
      alginate gel beads by a sol-gel process. The membrane has identical to Si-O-Si
      identical to bonds as well as electrostatic bonds between amino groups of AS and
      carboxyl groups of alginate. Permeability and stability were investigated for the
      membrane. Furthermore, rat islets encapsulated in the membrane (499 +/- 32
      microns in diameter, 1000 islets/recipient) were transplanted to the peritoneal
      cavities of the mice with streptozotocin-induced diabetes. Our data show that the
      membrane had the molecular weight cut-off point of between 70 and 150 kDa, and
      hardly inhibited the permeation of glucose and insulin. The Alg/AS/Alg
      microcapsule was more stable than the well-known Alg/poly-L-lysine (PLL)/Alg
      microcapsule. After 30 days of soaking in stimulated body fluid, the percentages
      of intact microcapsule were 98.4 +/- 0.5 (mean +/- SEM)% and 88.0 +/- 1.5% (p <
      0.001) for the Alg/AS/Alg and Alg/PLL/Alg microcapsules, respectively. The
      maximum maintenance period of normoglycemia was 105 days without administration
      of immunosuppressive drugs.

PMID- 12194521
TI  - The effect of microgeometry, implant thickness and polyurethane chemistry on the
      foreign body response to subcutaneous implants.
AB  - We addressed the effect of implant thickness, implant porosity, and polyurethane
      (PU) chemistry on angiogenesis and on the foreign body response in rats. The
      following materials were implanted subcutaneously for 7 weeks then excised for
      histologic analysis: a solid PU; a solid polyurethane with silicone and
      polyethylene oxide (PU-S-PEO); porous expanded polytetrafluoroethylene (ePTFE);
      and porous polyvinyl alcohol sponge (PVA). Two thicknesses of PU-S-PEO were
      compared: 300 microns (thin) and 2000 microns (thick). Foreign body capsule (FBC)
      thickness was much less in PU-S-PEO implants than in PU implants. In addition,
      FBC were thinner in thin implants than in thick implants. FBC was much more dense
      in solid implants than in porous implants. As compared with solid implants,
      porous implants (PVA and ePTFE) led to a marked increase in the number of
      microvessels that developed adjacent to the implant, as observed both with
      hematoxylin/eosin staining and with an immunohistochemical anti-endothelial
      stain. We conclude that the polyethylene oxide and silicone moieties in PU reduce
      the thickness of the subsequent FBC. In addition, thin implants lead to a thin
      FBC. Porous implants (PVA and ePTFE) cause more angiogenesis than solid implants.
      These results may have implications for the measurement of blood-derived analytes
      by biosensors.

PMID- 12194522
TI  - Large-scale gene expression analysis of osteoblasts cultured on three different
      Ti-6Al-4V surface treatments.
AB  - To improve implant biocompatibility, we developed a simple cost-effective thermal
      surface treatment allowing an increase in the oxide layer thickness of a titanium
      (Ti) alloy used in orthopaedic implants. The goal of this study was to test in
      vitro the reaction of osteoblasts to the developed surface treatment and to
      compare it to the osteoblast reaction to two other surface treatments currently
      used in the practice of implant surgery. Quantification of osteoblast gene
      expression on a large scale was used in this study. The kinetics of gene
      expression over 120 h was followed for 58 genes to quantify the effect of the
      developed surface treatment. Twenty eight genes were further selected to compare
      the effects of surface treatments on osteoblasts. Based on the genes studied, we
      could propose a general pathway for the cell reaction according to the surface
      treatments used: (1) metal ion release changes the time course of gene expression
      in the FAK pathway; (2) once the accumulation of metal ions released from the Ti
      surface exceeds a threshold value, cell growth is diminished and apoptosis may be
      activated; (3) PTK up-regulation is also induced by metal ion release; (4) the
      expression of Bcl-2 family and Bax may suggest that metal ions induce apoptosis.
      The developed treatment seems to increase the Ti-6Al-4V biocompatibility as
      highlighted by the lower impact of this treatment by the different pathways
      studied, on the lower inflammatory reaction that could be induced, as well as by
      the lower induced osteoblast apoptosis compared to the two other surface
      treatments.

PMID- 12194523
TI  - Swelling behavior of a genetically engineered silk-elastinlike protein polymer
      hydrogel.
AB  - The influence of environmental conditions such as pH, temperature, and ionic
      strength on the equilibrium swelling ratio of physically crosslinked networks of
      a genetically engineered silk-elastinlike protein-based copolymer (SELP) with an
      amino acid repeat sequence of [(GVGVP)4GKGVP(GVGVP)3(GAGAGS)4]12 was
      investigated. The effects of gelation cure time and initial polymer concentration
      on the equilibrium swelling ratio and soluble fraction of the hydrogels were also
      studied. It was found that the soluble fraction linearly correlated with the
      initial polymer concentration at higher gelation times. Soluble fraction results
      suggest that final hydrogel water content may be controlled by both initial
      polymer concentration and gelation time. Equilibrium swelling studies
      demonstrated that these hydrogels are relatively insensitive to environmental
      changes such as pH, temperature, and ionic strength. Over the concentration range
      studied, it was found that an increase in gelation time at 37 degrees C resulted
      in lower hydrogel weight equilibrium swelling ratios, which corresponds to less
      soluble polymer released post-gelation. Together, these results have implications
      for the controlled delivery of bioactive agents from silk-elastinlike hydrogels.

PMID- 12194524
TI  - Effect of micro-roughness produced by TiO2 blasting--tensile testing of bone
      attachment by using coin-shaped implants.
AB  - The aim of the present study was to examine bone response to micro-rough titanium
      implants. Forty coin-shaped implants were divided into eight groups according to
      their surface roughness. The first group had electropolished surfaces. The
      surfaces of implant groups 2-8 were blasted with TiO2 particles with incremental
      grain sizes ranging from 7.5-12.5 to 270-330 microns. Five implants from each
      group were placed into the cortical bone of the proximal tibia in New Zealand
      Black rabbits. To avoid bone overgrowth during the retention phase the implants
      were fitted into tight polytetrafluoroethylene (PTFE) caps leaving only the flat
      test surface exposed to bone. The healing period was set to 10 weeks, and
      implants with attached bone were evaluated using a tensile testing machine. In
      groups 1-7 a significant correlation between the micro-roughness of the implant
      surfaces and retention strength was observed. Maximum bone bonding was observed
      with implants blasted with 180-220 microns grain size (group 7). Blasting with
      larger TiO2 particles appeared to decrease the effect. The findings suggest that
      the best grain size of TiO2 particles for optimising retention of titanium
      implants in cortical bone should be in the 180-220 microns range.

PMID- 12194525
TI  - Why degradable polymers undergo surface erosion or bulk erosion.
AB  - A theoretical model was developed that allows to predict the erosion mechanism of
      water insoluble biodegradable polymer matrices. The model shows that all
      degradable polymers can undergo surface erosion or bulk erosion. Which way a
      polymer matrix erodes after all depends on the diffusivity of water inside the
      matrix, the degradation rate of the polymer's functional groups and the matrix
      dimensions. From these parameters the model allows to calculate for an individual
      polymer matrix a dimensionless 'erosion number' epsilon. The value of epsilon
      indicates the mode of erosion. Based on epsilon, a critical device dimension
      Lcritical can be calculated. If a matrix is larger than Lcritical it will undergo
      surface erosion, if not it will be bulk eroding. Lcritical values for polymers
      were estimated based on literature data. Polyanhydrides were found to be surface
      eroding down to a size of approximately Lcritical = 10(-4) m while poly(alpha
      hydroxy esters) matrices need to be larger than Lcritical = 10(-1) m to lose
      their bulk erosion properties. To support our theoretical findings it was shown
      experimentally that poly(alpha-hydroxy ester) matrices, which are considered
      classical bulk eroding materials, can also undergo surface erosion.

PMID- 12194526
TI  - Detection of slime production by means of an optimised Congo red agar plate test
      based on a colourimetric scale in Staphylococcus epidermidis clinical isolates
      genotyped for ica locus.
AB  - This investigation was conduced on a collection of 113 S. epidermidis strains
      isolated from biomaterial-associated infections. All strains were examined both
      for the presence of icaA and icaD genes responsible for slime synthesis by a PCR
      method and for the in vitro slime production ability by the Congo red agar (CRA)
      plate test. In the present study, the original CRA test was optimised adopting a
      six-colour reference scale for a fine classification of colonies colours. The six
      colour tones of the scale were as follows: very black (vb), black (b), almost
      black (ab), which were considered as positive results, and bordeaux (brd), red
      (r), and very red (vr), interpreted as negative. 57.5% of all the strains were
      found to be icaA icaD-positive as well as slime-forming onto CRA, exhibiting the
      following colonies colours: vb (35.4%); b (15.9%); ab (6.2%). The percentage of
      icaA icaD-negative strains was 42.5% and all of them were negative onto CRA: brd
      (19.5%), r (14.2%), vr (8.8%). The comparison of colour classification with the
      information on ica genes confirmed the validity of the scale adopted, providing
      support to the criteria used for a correct interpretation of the colonies colour
      during the execution of the CRA test. Overall these results indicate a fine
      consistency between these two experimental methods and a good reliability of CRA
      plate test, especially when this is supported by a colourimetric scale.

PMID- 12194527
TI  - Stability of polyethylene oxide in matrix tablets prepared by hot-melt extrusion.
AB  - The thermal stability of polyethylene oxide (PEO) in sustained release tablets
      prepared by hot-melt extrusion was investigated. The weight average molecular
      weight of the polymer was studied using gel permeation chromatography. The
      chemical stability of PEO was found to be dependent on both the storage and
      processing temperature, and the molecular weight of the polymer. Storage of the
      polymer above its melting point significantly increased polymer degradation, and
      the degradation process was accelerated as the molecular weight was reduced. The
      thermal stability of PEO MW = 1,000,000 (PEO 1 M) in sustained release
      chlropheniramine maleate (CPM) tablets prepared by hot-melt extrusion was found
      to depend on the processing temperature and screw speed. Lower molecular weight
      PEO MW = 100,000 (PEO 100 K) was demonstrated to be a suitable processing aid for
      PEO 1 M. Incorporation of PEO 100 K reduced degradation of PEO 1 M and did not
      alter the release rate of CPM. Vitamin E, Vitamin E Succinate and Vitamin E TPGS
      were found to be suitable stabilizers for PEO, however, ascorbic acid was shown
      to degrade the polymer in solution. Thermal analysis demonstrated that Vitamin E
      Succinate and Vitamin E TPGS were dispersed at the molecular level in hot-melt
      extruded tablets. Solubilized Vitamin E Succinate and Vitamin E TPGS suppressed
      the melting point of the polyethylene oxide. Drug release rates from hot-melt
      extruded tablets stabilized with antioxidants were found to be dependent on the
      hydrophilic nature of the antioxidant.

PMID- 12194528
TI  - Progressive failure analysis of laminated composite femoral prostheses for total
      hip arthroplasty.
AB  - In this research program, a numerical method was developed to predict the
      progressive failure of a thick laminated composite femoral component for total
      hip arthroplasty. A 3-D global/local technique was used to capture the overall
      structural response of this system while also enabling the 3-D ply level stress
      state to be determined efficiently and accurately. Different failure criteria and
      different material degradation models were incorporated as individual subroutines
      in the numerical method, giving it the flexibility to model a wide range of
      materials and structures. Numerical modeling was also conducted to design
      experimental test methods for component fatigue testing that closely simulate in
      vivo loading conditions. Parametric studies were then conducted with the
      numerical model of the experimental system and the results were compared to the
      actual experimentally determined damage behavior of fabricated laminated
      composite femoral component to assess which parameter set most accurately
      predicted the actual damage development behavior. The best fitting parameter set
      was then applied to the failure problem of the composite hip prosthesis implanted
      in an anatomically modeled femur to predict in vivo performance. This work
      provides a ply level understanding of the damage behavior of laminated composite
      femoral components and a numerical tool which can serve as a guide for the design
      of fatigue resistant implants made from composite material for this and other
      implant applications.

PMID- 12194529
TI  - Microstructural dependence on relevant physical-mechanical properties on SiO2
      Na2O-CaO-P2O5 biological glasses.
AB  - Bioactive glasses of the system SiO2-Na2O-CaO-P2O5 have been prepared by the
      normal melting and annealing technique. The elastic moduli, attenuation, Vickers
      hardness, fracture toughness and fracture surface energy have been obtained using
      the known method at room temperature. The temperature dependence of elastic
      moduli and attenuation measurements have been extended over a wide range of
      temperature from 150 to 500 K. The SiO2 content dependence of velocities,
      attenuation, elastic moduli, and other parameters show an interesting observation
      at 45 wt% of SiO2 by exhibiting an anomalous behaviour. A linear relation is
      developed for Tg, which explores the influence of Na2O on SiO2-Na2O-CaO-P2O5
      bioactive glasses. The measured hardness, fracture toughness and fracture surface
      energy show a linear relation with Young's modulus. It is also interesting to
      note that the observed results are functions of polymerisation and the number of
      non-bridging oxygens (NBO) prevailing in the network with change in SiO2 content.
      The temperature dependence of velocities, attenuation and elastic moduli show the
      existence of softening in the glass network structure as temperature increases.

PMID- 12194530
TI  - Preparation and in vitro evaluation of porous silica gels.
AB  - Porous silica gels with high surface areas were prepared from
      tetraethylothosilicate and polyacrylic acid (PAA) of high molecular weight in
      acidic media by a sol-gel method. PAA content and ageing temperatures were varied
      in order to obtain different microstructures. Samples were sintered at
      temperatures up to 400 degrees C, and subjected to in vitro evaluation by soaking
      them in acellular inorganic solutions at 37 degrees C and pH 7.3. Surface
      precipitation of carbonate-apatite on some of the gels was observed by FTIR
      spectroscopy, scanning electron microscopy and EPMA. Silica dissolution and re
      precipitation phenomena were also observed. The relationship between both
      phenomena during the in vitro test is discussed mainly in terms of structural and
      microstructural features of the gel.

PMID- 12194531
TI  - Mechanical properties and in vitro cell compatibility of hydroxyapatite ceramics
      with graded pore structure.
AB  - In order to improve the mechanical strength of hydroxyapatite (HA) ceramics used
      as osteoimplants and to enhance cellular penetration functionally graded ceramics
      with a transition in porosity from the surface towards the centre were designed.
      The multilayer structures were prepared by multiple tape casting based on an
      aqueous HA slurry containing polybutylmethacrylate (PBMA) spheres with diameters
      ranging from 100 to 300 microns. After burning out the PBMA, pores of 70-200
      microns were generated. The pore-graded laminates were sintered at temperatures
      between 1250 degrees C and 1450 degrees C. Bending strength of the pore-graded
      ceramics was approximately 50% higher as compared to HA of the same pore volume
      fraction but without gradient structure. The materials were tested in vitro for
      attachment and activity of osteoblast-like MC3T3-E1 cells over a period of 3
      weeks. Cells formed confluent layers on the ceramic surface, penetrated into the
      graded porosity ranging from 100-150 microns to 250-300 microns in size and
      showed increasing alkaline phosphatase activity over 3 weeks. The results
      demonstrated initial in vitro cell compatibility of the functionally graded HA
      materials and their potential as osteoimplants.

PMID- 12194532
TI  - Effect of hydroxyapatite morphology/surface area on the rheology and
      processability of hydroxyapatite filled polyethylene composites.
AB  - The commercial success of hydroxyapatite (HA) filled polyethylene composite has
      generated growing interest in improving the processability of the composite. A
      number of synthetic procedures and post synthesis heat treatment of HA has lead
      to the availability of powders with widely varying morphological features. This
      paper addresses the effect of morphological features of HA on the rheology and
      processability of an injection-moulding grade HA-HDPE composite. The results
      showed that low surface area HA filled composite exhibited better injection
      processing characteristics through improved rheological responses. The effect of
      reducing the surface area of the filler is to require less polyethylene to wet
      the filler and allows more polyethylene to be involved in the flow processes.
      These changes reduced the temperatures and pressures required for successful
      processing.

PMID- 12194534
TI  - Population pharmacokinetic analysis of the major metabolites of capecitabine.
AB  - Capecitabine has been developed as an orally administered tumor selective
      fluoropyrimidine for use in the treatment of breast and colorectal cancer. The
      metabolic pathway for capecitabine includes 5'-deoxy-5-fluorocytidine (5'-DFCR)
      and 5'-deoxy-5-fluorouridine (5'-DFUR), which is then converted to the
      pharmacologically active agent 5-fluorouracil (5-FU). A previous analysis showed
      that systemic exposure to 5'-DFUR and alpha-fluoro-beta-alanine (FBAL), a
      catabolite of 5-FU, was predictive of dose limiting toxicities. Therefore, a
      multi-response population pharmacokinetic (PK) model for the description of
      plasma concentrations of 5'-DFUR, 5-FU and FBAL following oral administration of
      capecitabine was developed using NONMEM. PK data from a bioequivalence study in
      24 patients with various solid tumors were used to develop the PK structural part
      of the population PK model. The 5'-DFUR, 5-FU and FBAL plasma concentrations were
      described by a linear disposition PK model with first order absorption and lag
      time. Sparse plasma concentration data from 54 phase II breast cancer patients
      were added to the bioequivalence data and the influence of covariates on the
      apparent oral clearances of 5'-DFUR, 5-FU and FBAL and on the apparent volume of
      distribution of FBAL was investigated. This was conducted by including all
      significant (p < 0.05) single covariate-PK parameter pairs in the full PK model,
      followed by one by one deletion (p < 0.001) from the population model.
      Statistically significant effects were found for the influence of gender, body
      surface area and total bilirubin on 5'-DFUR clearance and the influence of
      creatinine clearance on FBAL clearance. However, none of these effects were
      considered to have clinical relevance.

PMID- 12194533
TI  - Fifth-generation model for corticosteroid pharmacodynamics: application to steady
      state receptor down-regulation and enzyme induction patterns during seven-day
      continuous infusion of methylprednisolone in rats.
AB  - A fifth-generation model for receptor/gene-mediated corticosteroid effects was
      proposed based on results from a 50 mg/kg i.v. bolus dose of methylprednisolone
      (MPL) in male adrenalectomized rats, and confirmed using data from other acute
      dosage regimens. Steady-state equations for receptor down-regulation and tyrosine
      aminotransferase (TAT) enzyme induction patterns were derived. Five groups of
      male Wistar rats (n = 5/group) were subcutaneously implanted with Alzet mini
      pumps primed to release saline or 0.05, 0.1, 0.2, and 0.3 mg/kg/hr of MPL for 7
      days. Rats were sacrificed at the end of the infusion. Plasma MPL concentrations,
      blood lymphocyte counts, and hepatic cytosolic free receptor density, receptor
      mRNA, TAT mRNA, and TAT enzyme levels were quantitated. The pronounced steroid
      effects were evidenced by marked losses in body weights and changes in organ
      weights. All four treatments caused a dose-dependent reduction in hepatic
      receptor levels, which correlated with the induction of TAT mRNA and TAT enzyme
      levels. The 7 day receptor mRNA and free receptor density correlated well with
      the model predicted steady-state levels. However, the extent of enzyme induction
      was markedly higher than that predicted by the model suggesting that the usual
      receptor/gene-mediated effects observed upon single/intermittent dosing of MPL
      may be countered by alterations in other aspects of the system. A mean IC50 of
      6.1 ng/mL was estimated for the immunosuppressive effects of methylprednisolone
      on blood lymphocytes. The extent and duration of steroid exposure play a critical
      role in mediating steroid effects and advanced PK/PD models provide unique
      insights into controlling factors.

PMID- 12194535
TI  - Influence of arterial vs. venous sampling site on nicotine tolerance model
      selection and parameter estimation.
AB  - In this modeling study we utilize previously published nicotine pharmacokinetic
      (PK) and pharmacodynamic (PD, heart rate) data to investigate the influence of PK
      sampling site (venous vs. arterial) on the selection of a specific PD tolerance
      model and estimation of its parameters. We describe a general model for tolerance
      which includes as special cases feedback (TF), and kinetic based tolerance (TK)
      models. A TK model has arterial plasma drug concentrations (Ca) driving
      (hypothetical) effect (Ce) and antagonist (Cm) site concentrations, which drive a
      non-feedback effect (Enf): tolerance depends on the relative rate of
      equilibration of Ce and Cm with Ca. The TF model adds feedback which makes
      tolerance depend on Enf, not just on drug kinetics for nicotine. The arterial
      sampling-analysis (PKPDa) has Ca driving Ce and Cm. The venous-sampling-analysis
      (PKPDv) does the same but estimates Ca from venous data by means of
      deconvolution. A TF model (with Cm = Ce) was always selected in the PKPDa.
      According to this model tolerance developed rapidly with a median half-life of
      6.6 min, and median decrease of effect due to tolerance of 31%. Different
      variants of the TF or TK models were selected in the PKPDv. Parameter estimates
      for PKPDv show higher variability, and, for the TF model, lower rate and extent
      of tolerance development and threefold increase in EC50. The study shows that (i)
      TF models are more appropriate than TK models to describe nicotine effect data,
      (ii) venous sampling may lead to incorrect model selection and inaccurate and
      imprecise parameter estimation in respect to arterial sampling, and (iii)
      arterial sampling should be preferred for accurate (non-steady-state) PD
      modeling.

PMID- 12194536
TI  - Determination of an optimal dosage regimen using a Bayesian decision analysis of
      efficacy and adverse effect data.
AB  - One of the aims of Phase II clinical trials is to determine the dosage regimen(s)
      that will be investigated during a confirmatory Phase III clinical trial. During
      Phase II, pharmacodynamic data are collected that enables the efficacy and safety
      of the drug to be assessed. It is proposed in this paper to use Bayesian decision
      analysis to determine the optimal dosage regimen based on efficacy and toxicity
      of the drug oxybutynin used in the treatment of urinary urge incontinence. Such
      an approach results in a general framework allowing modeling, inference and
      decision making to be carried out. For oxybutynin, the repeated measurement
      efficacy and toxicity data were modeled using nonlinear hierarchical models and
      inferences were based on posterior probabilities. The optimal decision in this
      problem was to determine the dosage regimen that maximized the posterior expected
      utility given the prior information on the model parameters and the patient
      response data. The utility function was defined using clinical opinion on the
      satisfactory levels of efficacy and toxicity and then combined by weighting the
      relative importance of each pharmacodynamic response. Markov chain Monte Carlo
      (MCMC) methodology implemented in Win-BUGS 1.3 was used to obtain posterior
      estimates of the model parameters, probabilities and utilities.

PMID- 12194537
TI  - A note on sample size calculation in bioequivalence trials.
AB  - Based on fundamental pharmacokinetic relationships, a multiplicative model is
      commonly used in bioequivalence trials. With regard to the parametric analysis,
      this implies the assumption of a lognormal distribution. Statistical methods for
      sample size calculation has been consolidated over the last years. Recently,
      methods for sample size calculation in the additive model, i.e., under normality
      assumption, were presented. Hence, these methods are reviewed from a statistical
      and regulatory point of view.

PMID- 12194538
TI  - Sample size calculation in bioequivalence trials.

PMID- 12194539
TI  - Screening for anxiety in an epidemiological sample: predictive accuracy of
      questionnaires.
AB  - The study examined the predictive accuracy of selected questionnaires when
      screening for anxiety in a representative epidemiological sample of young female
      adults (N = 1877). All participants were diagnosed using a structured diagnostic
      interview. Anxiety questionnaires included global as well as specific measures
      (Beck Anxiety Inventory (BAI), Symptom Checklist, Anxiety Sensitivity Index
      (ASI), Fear Questionnaire (FQ), Mobility Inventory (MI)). Sensitivity,
      specificity, positive and negative predictive power were computed for two
      screening decisions: (1) identifying any anxiety disorder or (2) identifying a
      specific anxiety disorder (agoraphobia) within the total sample and the clinical
      subsample. Due to naturalistic (low) base rates in epidemiological samples,
      diagnostic indices were lower than those previously reported. However,
      questionnaire data proved useful when a specific disorder was targeted
      (agoraphobia) and specific symptoms were operationalized.

PMID- 12194540
TI  - Anxiety sensitivity among children of parents with anxiety disorders: a
      controlled high-risk study.
AB  - We investigated whether parental anxiety was related to anxiety sensitivity (AS)
      in offspring. Subjects were 261 offspring (aged 6-17 years) of parents with
      lifetime DSM-IV anxiety and/or mood disorders, and 79 offspring of parents with
      no lifetime anxiety, mood, or psychotic disorder. Parents and offspring were
      interviewed by blind clinicians. Children were administered the Child Anxiety
      Sensitivity Index (CASI). There were no significant differences between CASI
      scores of the offspring of parents with anxiety and/or mood disorders, and
      offspring of comparison parents. We conclude that parental anxiety or mood
      disorder does not predispose offspring to high anxiety sensitivity.

PMID- 12194541
TI  - The relationship between memories for childhood teasing and anxiety and
      depression in adulthood.
AB  - This study explored the relationship between memories for childhood teasing and
      anxiety and depression in adulthood. A Teasing Questionnaire (TQ) was developed
      that measured the degree to which people recall having been teased about 20
      different topics during childhood. The TQ was completed by a sample of 514
      undergraduates who also completed established measures of anxiety and depression.
      A one-factor model best accounted for the variance in TQ scores, and the total
      score was shown to have strong internal consistency. Scores on the TQ were
      significantly and positively related to scores on measures of current depression,
      trait anxiety, social anxiety, and anxiety sensitivity. Tests of dependent
      correlations showed that remembering having been teased during childhood was not
      differentially related to depression and trait anxiety in adulthood. However,
      differential relationships between reports of teasing and specific forms of
      anxiety were shown. Limitations of the study were discussed, as were suggestions
      for future research in the more general arena of childhood peer relations and
      adult psychopathology.

PMID- 12194542
TI  - Heavy drinking among college students is influenced by anxiety sensitivity,
      gender, and contexts for alcohol use.
AB  - In order to quantify relationships between anxiety sensitivity and situational
      antecedents to heavy alcohol consumption, 245 university student drinkers
      completed the anxiety sensitivity index-revised (ASI-R) and the inventory of
      drinking situations (IDS-42). The observed correlations indicated that anxiety
      sensitivity is related to negatively reinforced drinking, positively reinforced
      drinking, and temptation-motivated drinking. However, anxiety sensitivity is most
      clearly implicated as a factor in negatively reinforced drinking, i.e., drinking
      followed by "tension reduction." Additionally, the relationship between anxiety
      sensitivity and negatively reinforced drinking is stronger among males than among
      females. The results point to anxiety sensitivity and gender as interacting
      individual difference variables that influence incidence of negatively reinforced
      heavy drinking among college students.

PMID- 12194543
TI  - Nightmare frequency in sexual assault survivors with PTSD.
AB  - Sexual assault survivors with post-traumatic stress disorder (PTSD) were assessed
      for frequency of nightmares, measured retrospectively on the Nightmare Frequency
      Questionnaire (NFQ) and prospectively on nightmare dream logs (NLOG).
      Retrospective frequency was extremely high, averaging occurrences every other
      night and an estimated number of nightmares greater than five per week. Test
      retest reliability data on the NFQ yielded weighted kappa coefficients of .85
      (95% CI, .74-.95) for nights and .90 (95% CI, .83-.97) for nightmares.
      Correlations between retrospective and prospective nightmare frequencies ranged
      between .53 (P = .001) for nights and .63 (P = .001) for nightmares. Correlations
      between frequency and distress measures (anxiety, depression, post-traumatic
      stress) yielded coefficients ranging from (r = .28-.53). Compared with intrusive,
      cumbersome and time-consuming prospective measurements, the NFQ appears reliable,
      convenient, and equally useful in assessing nightmare frequency in a group of
      sexual assault survivors. Nightmare frequency, prevalence, distress and
      impairment are discussed.

PMID- 12194544
TI  - Post-traumatic symptoms, emotional distress and quality of life in long-term
      survivors of breast cancer: a preliminary research.
AB  - The present study is a preliminary study assessing long-term psychological
      effects in survivors of breast cancer. Thirty-nine long-term female survivors of
      breast cancer were compared with 39 matched women who had not been exposed to any
      chronic disease regarding post-traumatic stress disorder (PTSD), quality of life
      (QoL), emotional distress and coping styles. Survivors revealed significantly
      higher rates of full and partial PTSD, scored significantly higher on emotional
      distress, scored significantly lower on physical and psychological QoL and
      exhibited coping styles significantly different from those of the control group.
      PTSD was associated with the coping style of suppression. Multiple regression
      analysis showed that receiving chemotherapy and disease stage, as well as the
      interaction between chemotherapy and disease stage, were significant predictors
      of hyperarousal. The findings show that post-traumatic symptoms are a common
      sequel after recovery from cancer. Furthermore, finding suggest a conceptual
      distinction between PTSD symptoms and QoL in the study of long-term effects of
      cancer.

PMID- 12194545
TI  - Open trial of cognitive behavior therapy for childhood obsessive-compulsive
      disorder.
AB  - Examined the utility of CBT for childhood obsessive-compulsive disorder (OCD)
      including a preliminary exploration of predictors of response to this form of
      treatment. A total of 42 youngsters (mean age 11.8 years, 60% female, 52% on
      medication at baseline) with DSM-IV OCD were treated openly using a
      developmentally sensitive treatment protocol based on exposure plus response
      prevention (ERP). The treatment response rate (CGI < 2) was 79% with a mean
      decrease from baseline in NIMH global scores of 45%. Response was not related to
      age, gender, baseline medication status, comorbid symptomatology, or therapist
      experience. Poorer outcome was associated with more severe obsessions and greater
      OCD-related academic impairment at baseline. When presented in a developmentally
      appropriate manner, CBT is a useful treatment for childhood OCD. Controlled
      trials are needed to provide a more rigorous test of this treatment approach and
      provide better information regarding potential mediators and moderators of
      outcome.

PMID- 12194546
TI  - Cross validation of the Social Anxiety Scale for Adolescents in a high school
      sample.
AB  - Social anxiety disorder in adolescents is increasingly recognized as a common
      condition that may precede onset of other mental health problems. However, few
      measures are currently available to screen for adolescent social anxiety, and
      little is known about their psychometric characteristics in school-based samples.
      To this end, the present study was undertaken as a psychometric cross validation
      of the Social Anxiety Scale for Adolescents (SAS-A). Exploratory and Confirmatory
      Factor Analyses (CFA) supported the original 3-factor structure of the SAS-A but
      retained fewer items than in the original scale. The revised scales demonstrated
      good internal consistency as well as criterion and concurrent validity. Despite
      including fewer items, psychometric characteristics of the revised scales were
      equivalent to or stronger than those reported in previous studies of the measure.
      As such, the present study provides initial support for the utility of the
      revised SAS-A as a measure of social anxiety in adolescent school samples.

PMID- 12194547
TI  - Pre- and postoperative psychological characteristics in morbidly obese patients.
AB  - BACKGROUND: Quality of life is poor in morbidly obese patients, because of
      impaired physical and psychosocial functioning. Surgical treatment offers long
      term weight reduction and amelioration of most associated comorbidities. Studies
      of the effect of weight loss on patients' mental well-being are required, because
      discrimination and psychopathologic consequences represent a heavy burden.
      PATIENTS AND METHODS: 53 patients were interviewed 48 hours before vertical
      banded gastroplasty (VBG) by the psychiatric team and completed the self
      administered SCL-90-R questionnaire. Correlations of patients' age, educational
      level, employment, duration of obesity and family conditions were investigated
      and compared with the degree of obesity 10-12 months postoperatively. 35 patients
      returned to psychiatric follow-up and completed the same questionnaire, and the
      various psychopathologic characteristics were compared to the preoperative ones.
      RESULTS: Females had statistically significant higher scores in all
      psychopathologic parameters studied; more obvious differences were seen in
      depression (P < 0.001), paranoid ideation (P < 0.001) and interpersonal
      sensitivity (P < 0.001). Correlations of several demographic characteristics with
      the patients' preoperative BMI were negative. 10-12 months following VBG,
      statistically significant improvement in the parameters of phobic anxiety,
      obsessions-compulsions, paranoid ideation and interpersonal sensitivity (P <
      0.05) were found. CONCLUSION: Pre-existing psychopathology was more obvious among
      females, and improved significantly following successful weight loss 1 year
      postoperatively.

PMID- 12194548
TI  - The effect of Roux limb lengths on outcome after Roux-en-Y gastric bypass: a
      prospective, randomized clinical trial.
AB  - BACKGROUND: The effect of limb-length on weight loss after Roux-en-Y gastric
      bypass (RYGBP) is controversial; hence, the optimal limb-lengths have not been
      determined. This study evaluated the effect of different limb-lengths on weight
      loss after RYGBP. METHODS: The study was a prospective randomized clinical trial
      in which patients undergoing RYGBP (110 F, 24 M; mean age 39.7) were randomized
      as follows: BMI < or = 50 (N = 69): A-75 cm (N = 35) vs B-150 cm alimentary limb
      (N = 34) and C-150 cm (N = 33) vs D-250 cm alimentary limb (N = 31). All other
      aspects of the operation were identical. Patients were followed at 2 weeks, 6
      weeks, 6 months, 12 months, 18 months, 24 months and yearly thereafter. RESULTS:
      There were no significant differences in age, sex, race, initial BMI, or excess
      weight between patients assigned to groups A vs B and C vs D. Postoperative
      nutritional intake was also similar between groups. Within each weight category,
      there were no differences in mean weight loss, change in BMI, and % excess weight
      lost (EWL) over time. When the number of patients achieving 50% EWL was
      evaluated, there was no difference between groups with a BMI < or = 50 kg/m2;
      however, among patients with a BMI > 50 kg/m2, a significantly greater percentage
      of those having a 250-cm limb achieved > 50% EWL at 18 months postoperatively.
      This difference was lost at 24 and 36 months, possibly due to the small sample
      size. CONCLUSIONS: In patients with a BMI < or = 50, there appears to be no
      advantage to longer limb-lengths. In patients with BMI > 50, however, these data
      suggest that longer alimentary limb-lengths may be associated with a higher
      percent of patients achieving > 50% EWL. Longer follow-up studies of the effects
      of limb-length on success of RYGBP are indicated.

PMID- 12194549
TI  - Fully stapled gastric bypass with isolated pouch and terminal anastomosis: 1-3
      year results.
AB  - BACKGROUND: Roux-en-Y gastric bypass is a bariatric procedure of choice. There is
      evidence supporting a small isolated pouch and a wide anastomosis. Gastric
      vascular anatomy renders the ventral aspect less suited for anastomotic
      construction. The lesser curvature has abundant blood supply that should
      preferably not be interfered with. Terminal anastomosis is a logical choice.
      METHODS: We devised a way of making a fully stapled gastric bypass with complete
      separation of a pouch that empties dependently. The technique obviates the oral
      passage of the stapler anvil. Such a procedure facilitates the creation of an
      "end-of-pouch to end-of-jejunal limb" wide-diameter anastomosis and precludes the
      risk of staple-line disruption. RESULTS: Since October 1997 we have performed 227
      such anastomoses (146 primary, 81 reoperative procedures) in consecutive patients
      with no leaks, no gastro-gastric fistulas and no mortality. The postoperative
      hospital time was 3.6 (3-8) days (median, range). In primary operations baseline
      BMI was 47.5, 1-yr 29.7 and 3-yr 29.2. Corresponding values for reoperations were
      39.3, 30.8 and 31.5. Weight loss was adequate, and complications were limited to
      three anastomotic ulcers and two narrow stomas without visible ulcers but
      necessitating endoscopic dilatation. CONCLUSION: The technique confers
      distinctive advantages.

PMID- 12194550
TI  - Comparison of nutritional deficiencies after Roux-en-Y gastric bypass and after
      biliopancreatic diversion with Roux-en-Y gastric bypass.
AB  - BACKGROUND: Patients undergoing either Roux-en-Y gastric bypass (RYGBP) or
      biliopancreatic diversion (BPD) with RYGBP are at risk of developing metabolic
      sequelae secondary to malabsorption. We compared the differences in nutritional
      complications between these two bariatric operations. METHODS: A retrospective
      analysis of a prospective database was done. From June 1994 to December 2001, 243
      morbidly obese patients underwent various bariatric procedures at our
      institution. Of these patients, 79 (BMI 45.6 +/- SD = 4.9) who underwent RYGBP
      (gastric pouch 15 +/- 5 ml, biliopancreatic limb 60-80 cm, alimentary limb 80-100
      cm and common limb the remainder of the small intestine), and 95 super obese (BMI
      57.2 +/- 6.1) who underwent a BPD (gastric pouch 15 +/- 5 ml, biliopancreatic
      limb 150-200 cm, common limb 100 cm and alimentary limb the remainder of the
      small intestine), were selected and studied for the incidence of micronutrient
      deficiencies and level of serum albumin at yearly intervals postoperatively. A
      variety of nutritional parameters including Hb, Fe, ferritin, folic acid, vitamin
      B12 and serum albumin were measured preoperatively and compared postoperatively
      at 1, 3, 6, 12, 18 and 24 months, and yearly thereafter. RESULTS: Nutritional
      parameters were compared preoperatively and at similar periods postoperatively.
      No statistically significant (P < 0.05) difference in the occurrence of
      deficiency was observed between the groups for any of the nutritional parameters
      studied, except for ferritin, which showed a significant difference at the 2-year
      follow-up (37.7% low ferritin levels after RYGBP vs. 15.2% after BPD, P =
      0.0294). All of these deficiencies were mild, without clinical symptomatology and
      were easily corrected with additional supplementation of the deficient
      micronutrient, with no need for hospitalization. Regarding serum albumin, there
      was only one patient with a level below 3 g/dl in the RYGBP group and two in the
      BPD group. These three patients were hospitalized and received total parenteral
      nutrition for 3 weeks, without further complications. CONCLUSION: There was no
      significant difference in the incidence of deficiency of the nutritional
      parameters studied, except for ferritin, following RYGBP vs. BPD with RYGBP. The
      most common deficiencies encountered were of iron and vitamin B12. The incidence
      of hypoalbuminemia was negligible in both groups, with mean values above 4 g/dl.

PMID- 12194551
TI  - Laparoscopic reoperation for early complications of laparoscopic gastric bypass.
AB  - BACKGROUND: Laparoscopic Roux-en-Y gastric bypass (LRYGBP) is a popular operation
      for morbid obesity. Early complications can be treated successfully with a
      laparoscopic approach. We reviewed our experience with laparoscopic re
      exploration in the early postoperative period. METHODS: The initial 85 patients
      who underwent LRYGBP by two surgeons at a training hospital were reviewed. All
      patients who required re-exploration within the first 60 days postoperatively
      were considered. RESULTS: Nine patients underwent ten laparoscopic explorations.
      Mean BMI was 50 kg/m2. One patient underwent revision for proximal anastomotic
      obstruction at 58 days postoperatively. Three patients developed obstruction at
      the level of the transverse mesocolon secondary to cicatrix and required
      laparoscopic release of the scar tissue. Two patients required revision of the
      jejuno-jejunostomy. Internal hernia through the mesenteric defect at the level of
      the transverse mesocolon was the cause of bowel obstruction in two patients. One
      patient underwent lysis of adhesions between the left colon and the transverse
      mesocolon at 6 days postoperatively. One out of the ten laparoscopic re
      explorations was negative for any findings. Eight patients recovered without
      further complications and one patient required endoscopic dilatations of the
      proximal anastomosis. CONCLUSION: In the course of treating morbid obesity with
      laparoscopic intervention, complications will arise. Laparoscopic exploration for
      early complications is a safe and feasible option.

PMID- 12194553
TI  - Experience with Lap-band System up to 7 years.
AB  - BACKGROUND: Morbid obesity occurs in 2-5% of the population of Western countries.
      Laparoscopic adjustable silicone gastric banding was designed to be a minimally
      invasive, adjustable and reversible procedure for the treatment of morbid
      obesity. MATERIAL AND METHODS: The Lap-band System was evaluated retrospectively
      in a series of 543 patients. Data on preoperative aspects and postoperative
      outcome and weight loss patterns at up to 7 years follow-up (median follow-up 36
      months) are presented. RESULTS: The most important late complication was total
      and irreversible food intolerance due to proximal pouch dilatation, which
      occurred in 24 patients (4.6%). 20 of these patients (3.8%) had had a proximal
      pouch calibration with 25 cc; 4 patients were calibrated with 15 cc. The mean BMI
      had fallen from 44 kg/m2 to 33.2 kg/m2 and was stable after a follow-up of up to
      86 months (median 36 months). CONCLUSION: The Lap-band System is an effective
      procedure for achieving appreciable and stable weight loss at up to 7 years of
      follow-up (median 36 months). The minimally invasive approach was associated with
      a short hospital stay and a low rate of complications. Preoperative patient
      selection, detailed information and availability of the multidisciplinary team
      permitted us to achieve good longstanding results.

PMID- 12194552
TI  - Long-term results of laparoscopic adjustable gastric banding for the treatment of
      morbid obesity.
AB  - BACKGROUND: Since the first laparoscopic adjustable gastric banding (LAGB)
      operation on September 1, 1993, there have been important publications related to
      this procedure. The majority of the articles reported surgical technique and
      short-term results. Long-term results of LAGB are lacking. The authors report
      long-term data (at least 4 years) from 3 major bariatric centers in Belgium that
      perform LAGB routinely. METHODS: The 3 centers applied the same patient selection
      criteria, the same standard surgical technique, the same laparoscopic band (Lap
      Band) and the same follow-up program. 763 patients have been enrolled. Sex ratio
      was 22% male/78% female. Mean age was 34 years, and mean preoperative BMI was 42
      kg/m2. RESULTS: The follow-up rate was 90%, and the minimum follow-up time was 4
      years. The average BMI after 4 years was 30 kg/m2. Early complications were:
      gastric perforation 4 (0.5%); large bowel perforation 1 (0.1%); bleeding 1
      (0.1%); and conversion to open 10 (1.3%). Late complications were: erosion 7
      (0.9%); total food intolerance 59 (8%); access port problems 20 (2.5%); re
      operations 80 (11.1%); death 1 (0.1%). CONCLUSION: Long-term results of LAGB have
      been rarely reported, although publications on the procedure are copious. Our
      long-term data found that BMI evolution is good, the complication and re
      operation rates are acceptable and the overall long-term results of the Lap-Band
      system are good.

PMID- 12194554
TI  - Adjustable gastric and esophagogastric banding: a randomized clinical trial.
AB  - BACKGROUND: Adjustable gastric banding and esophagogastric banding may affect the
      function of the lower esophageal sphincter (LES) and esophageal motility in the
      long-term. Both methods were evaluated in a prospective randomized trial.
      MATERIALS AND METHODS: Group 1 comprised 28 patients who underwent laparoscopic
      adjustable gastric banding and Group 2 consisted of 24 patients in whom
      adjustable esophagogastric banding was performed. Swedish Adjustable Gastric
      Bands were used in all patients. Body mass index (BMI), perioperative
      complications and reflux symptoms were assessed and upper gastrointestinal
      endoscopy, esophageal barium studies, esophageal manometry and 24-hour esophageal
      pH-monitoring were performed pre- and postoperatively. 18 (Group 1) and 14 (Group
      2) patients completed the postoperative follow-up procedure after a median of 23
      and 24 months, respectively. RESULTS: Postoperatively the median BMI dropped
      equally in both groups. Perioperative complications requiring re-intervention
      were significantly more frequent in Group 2 than in Group 1. Heartburn improved
      equally in both groups following surgery; however, regurgitation and esophagitis
      were significantly more common in Group 2 than in Group 1.24-hour esophageal pH
      monitoring and the LES resting pressure improved equally in both groups, but
      there was a significant impairment of the LES relaxation and the esophageal
      peristalsis, which was more pronounced in Group 2 than in Group 1. This caused
      significant esophageal stasis as shown by barium studies. CONCLUSIONS: Both
      techniques, gastric and esophagogastric banding, provide effective weight loss in
      morbidly obese patients but affect the esophagogastric junction. Although both
      procedures strengthen the antireflux-barrier, LES relaxation becomes impaired,
      thus promoting esophageal dilatation and esophageal stasis. This is more
      pronounced following esophagogastric banding than following the classic
      procedure. Since the esophagogastric banding results in more complications
      requiring re-intervention, we believe that this procedure should not be used any
      more.

PMID- 12194555
TI  - Laparoscopic adjustable gastric banding: a prospective comparison of two commonly
      used bands.
AB  - BACKGROUND: Surgery for morbid obesity has increased since the introduction of
      the adjustable gastric bands (AGB), which can be placed laparoscopically. There
      are two AGB in wide use: the Swedish Adjustable Gastric Band (SAGB, Obtech), and
      the Lap-Band (Inamed Health). We present the results of a comparative study
      between the 2 AGB. METHODS: 101 patients with a minimal follow-up of 6 months
      were included. 49 patients received a Swedish Adjustable Gastric Band (SAGB), and
      the remaining 52 received the Lap-Band (LB). Postoperative weight loss and
      complications were compared at set intervals of 3 months in the first
      postoperative year, and 6 months in the years following. RESULTS: Mean follow-up
      was 9.9 months for the SAGB and 7.2 months for the LB. All but 5 procedures were
      performed laparoscopically. Mean operating-time was 102 minutes for the SAGB and
      86 minutes for the LB. No significant difference in complications was noted
      between the 2 AGB. 1 SAGB was repositioned and 2 were removed, compared to 2
      repositions and 2 removals of the LB. We excluded 5 patients with leakage of a
      SAGB due to technical failure. Mean preoperative weight kg/BMI of the SAGB
      patients was 133/45.3; in the LB patients 138/46.4. Mean weight loss at 6 months
      was 28 kg with the SAGB and 30 kg with the LB, and mean weight loss at 1 year 36
      kg and 38 kg respectively. After 2 years, weight loss was 46 kg and 42 kg
      respectively. CONCLUSION: There was no significant difference in postoperative
      weight loss and complications between the SAGB and the LB.

PMID- 12194556
TI  - Treatment of morbid obesity with intragastric balloon in association with diet.
AB  - BACKGROUND: The BioEnterics Intragastric Balloon (BIB, BioEnterics, Santa
      Barbara, CA) in association with restricted diet has been used for the treatment
      of obesity and morbid obesity. METHODS: Since March 1998, 322 BIB were placed in
      281 obese and morbidly obese patients; 73 patients were male and 208 female; mean
      age was 41.6 years (21-70); mean weight was 117.4 kg (67-229); mean BMI was 41.8
      kg/m2 (29-81); % excess weight was 62% (10-216). The balloon was inserted and
      removed endoscopically under general anesthesia. Patients were given a balanced
      diet of 1000 kcal/day. Also, for 18 months we compared 42 obese patients treated
      only with 1000 kcal/day diet (group A) with 31 obese patients subjected to BIB
      for 4 months + 1000 kcal/day diet (group B). RESULTS: After 4 months of balloon
      treatment, the mean weight loss was 13.9 kg and the mean reduction in BMI was
      4.8. Weight loss was greater in male patients. Weight loss was accompanied by an
      improvement of the diseases associated with obesity, in particular diabetes. In
      the diet vs BIB + diet study, BIB with diet produced a greater weight loss in a
      shorter time than diet alone. CONCLUSION: The best indications for BIB were:
      morbidly obese opatients (BMI > 40) and super-obese patients (BMI > 50) in
      preparation for bariatric operations; obese patients with BMI 35-40 with co
      morbilities in preparation for bariatric surgery; obese patients with BMI 30-35
      with a chronic disease otherwise unresolved; patients with BMI < 30 only in a
      multidisciplinary approach.

PMID- 12194557
TI  - The Proring-Band: a new device in the field of restrictive surgery: preliminary
      experience.
AB  - BACKGROUND: We have an 11-year experience with Silastic ring vertical gastroplasy
      (SRVG) by laparotomy (1991-1994), followed by SRVG by mini-laparotomy (1995
      2002), giving a total of 1,286 patients up to May 31, 2002. Searching for optimal
      results, we have utilized a new device; the Silastic ring has been replaced by
      the Proring-Band. METHODS: 174 mini-laparotomy SRVGs (mini-SRVG) were carried out
      with the Proring-Band from July 16, 2001 to May 31, 2002. RESULTS: The ring is
      more flexible, slightly elastic and white-colored. At the operation, handling,
      fixing to the stomach and extraction were easier. No immediate postoperative
      complications or overall morbidities were related to the new band. No side-effect
      has been noted. CONCLUSIONS: The Proring-Band appeared simpler in its use, during
      preparatory extra-body handling, placement and fixation. Considering its
      flexibility, its flat part and its smooth edges, the Proring-Band appears to
      present less risk of dysphagia, rupture and migration. This situation will be
      evaluated in a comparative blind study with a follow-up of more than 2 years. The
      Proring-Band ring is manufactured, sterilized and marketed by a pharmaceutical
      company. The use of this ring, provided as a medical device designed for
      restrictive surgery, assures to the surgeon a reproducibility of the material and
      of the sterilization conditions.

PMID- 12194558
TI  - Weakness after gastric bypass.
AB  - Two patients underwent gastric bypasses and had uneventful hospital courses. In
      the early postoperative periods, both developed severe, protracted vomiting,
      weakness, and hyporeflexia. After thorough laboratory and clinical evaluations by
      neurologists, the patients were diagnosed with Guillain-Barre syndrome, although
      there were many atypical features. The clinical presentations of these patients
      are very similar to case reports of nutritional polyneuropathy associated with
      gastric partitioning. This paper addresses the difficulties of differentiating
      these two diagnoses.

PMID- 12194559
TI  - Bariatric surgery in a patient with possible psychiatric contraindications.
AB  - Grade III obesity (BMI > 39.9 kg/m2) is considered a chronic disease where
      clinical and diet therapy show poor results, with high rates of relapse. The most
      consistent results are those obtained through surgical procedures. Several
      authors discuss the contraindications for the performance of anti-obesity
      operations. Psychiatric disorders are often considered contraindications to these
      operations, especially affective disorders, psychotic disorders and personality
      disorders. The authors report the case of a 37-year-old patient, with obesity
      history since the age of 12, and anorexiant abuse (amphetamine-derived
      substances) during 20 years, binge-eating episodes, purgative compensatory
      behaviors and recurrent depressive symptoms. She was submitted to anti-obesity
      surgery in August 2000 (BMI 40.2). The outcome is reported and a discussion of
      the possible psychiatric contraindications for the anti-obesity surgeries is
      proposed.

PMID- 12194560
TI  - Speech disfluency in centenarians.
AB  - Other than a single case presentation of a 105-year-old female, no other studies
      have addressed the speech fluency characteristics of centenarians. The purpose of
      this study was to provide descriptive information on the fluency characteristics
      of speakers between the ages of 100-103 years. Conversational speech samples from
      seven speakers were evaluated for the frequency and types of disfluencies and
      speech rate. The centenarian speakers had a disfluency rate similar to that
      reported for 70-, 80-, and early 90-year-olds. The types of disfluencies observed
      also were similar to those reported for younger elderly speakers (primarily whole
      word/phrase, or formulative fluency breaks). Finally, the speech rate data for
      the current group of speakers supports prior literature reports of a slower rate
      with advancing age, but extends the finding to centenarians. LEARNING OUTCOMES:
      As a result of this activity, participants will be able to: (1) describe the
      frequency of disfluency breaks and the types of disfluencies exhibited by
      centenarian speakers, (2) describe the mean and range of speaking rates in
      centenarians, and (3) compare the present findings for centenarians to the
      fluency and speaking rate characteristics reported in the literature.

PMID- 12194562
TI  - Gender and masculinity-femininity ratings of tracheoesophageal speech.
AB  - Tracheoesophageal (TE) speech is frequently characterized as low pitched and
      hoarse. In laryngeal speakers, these features are most often associated with
      males. Because lower pitch and hoarseness are anticipated for male and female TE
      speakers, one might predict that females are at risk for being perceived as male.
      The purposes of this pilot study were to assess the reliability and accuracy of
      listeners' perceptions of TE speaker gender and to evaluate the relationship
      between gender ratings and masculinity-femininity ratings. Twenty-five naive
      listeners rated the gender and the masculinity-femininity of 12 TE speakers from
      audio recordings of a reading passage. Listeners were able to reliably rate
      gender and masculinity-femininity. They accurately identified speaker gender at a
      high rate that was comparable for males and females. However, female speakers,
      despite being accurately identified as female, were at an elevated risk of being
      rated as masculine or neutral on the masculinity-femininity scale. LEARNING
      OUTCOMES: As a result of this activity, the participant will be able to: (1)
      describe the reliability and accuracy of listener perceptions of the gender and
      the degree of masculinity-femininity of TE speakers; and (2) discuss the
      relationship between TE speaker gender identification and masculinity-femininity
      ratings for males and females, respectively.

PMID- 12194561
TI  - Speech and language outcomes of children with bronchopulmonary dysplasia.
AB  - A prospective follow-up of very low birth weight infants (VLBW) with (n = 89) and
      without (n = 71) bronchopulmonary dysplasia (BPD) and Term control children (n =
      93) was conducted at 8 years of age. Groups were compared on measures of
      articulation, receptive and expressive language, verbal and performance IQ, oral
      motor skills and gross and fine motor skills. The BPD group demonstrated reduced
      articulation, receptive language skills, performance IQ, and overall gross and
      fine motor skills when compared to VLBW and Term groups. The BPD and VLBW groups
      did not differ on expressive language, oral motor skills, or verbal IQ. The
      groups also differed in enrollment in special classes and speech-language
      therapy, with almost half (48%) of the BPD group enrolled in speech-language
      therapy compared to 21% of the VLBW group, and 9% of the Term group. These
      results suggest that BPD may have adverse effects on speech development as well
      as on performance IQ, motor skills, and receptive language over and above the
      effects of VLBW. LEARNING OUTCOMES: (1) As a result of this activity the reader
      will be able to describe what BPD is and how it impacts speech and language. (2)
      As a result of this activity the reader will be able to discuss how children with
      VLBW with BPD differ from children with VLBW without BPD in their developmental
      outcomes.

PMID- 12194563
TI  - Graduate students with marginal abilities in communication sciences and
      disorders: prevalence, profiles, and solutions.
AB  - This paper addresses the special challenges encountered when working with
      graduate students whose academic and/or clinical performance is marginal or less
      than satisfactory. From a variety of perspectives including instructional,
      professional, financial, ethical, and legal, among others, working effectively
      with marginal students deserves serious and systematic consideration. The purpose
      of this paper is to present the results of a national survey that explore the
      prevalence, profiles, and documented impact of marginal students on professional
      training programs in speech-language pathology and audiology. Current strategies
      for prevention and intervention, factors inhibiting implementation of such
      strategies, and implications for the student and the program are discussed.
      LEARNING OUTCOMES: (1) To learn the prevalence, profiles, and documented impact
      of marginal students on professional preparation programs in communication
      sciences and disorders. (2) To become familiar with current strategies for
      prevention and intervention with marginal students, factors inhibiting
      implementation of such strategies, and implications for the student and the
      program. (3) To understand professional preparation as a system of academic,
      clinical, and supervisory instruction, including evaluation and due process;
      namely, a student's right, a program's responsibility. (4) To identify critical
      questions generated by this study that must be addressed by the professions and
      individual programs.

PMID- 12194564
TI  - Sensitivity to word order cues by normal and language/learning disabled adults.
AB  - Sixteen adults with language/learning disabilities (L/LD) and 16 adults who
      lacked a personal or familial history of L/LD participated in a study designed to
      test sensitivity to word order cues that signaled grammatical versus
      ungrammatical word strings belonging to an artificial grammar. In an exposure
      phase, participants heard word strings constructed of novel CVC words for a
      period of 5 min. In a test phase, participants were asked to judge new sentences
      as either obeying or violating the rules of the grammar they heard. L/LD
      participants performed significantly below the comparison group on this task. The
      results suggest that this skill, which emerges early in life for normal children,
      is problematic for adults with L/LD. LEARNING OUTCOMES: The reader will become
      familiar with a paradigm that allows assessment of rapid learning of word order
      rules and how this learning differs for normal and language/learning disabled
      adults.

PMID- 12194565
TI  - Cataract surgery in uveitis.
AB  - PURPOSE: To study the visual outcome of cataract surgery in eyes with uveitis.
      METHODS: A retrospective analysis of patients with uveitis operated for cataract.
      RESULTS: 106 eyes of 89 patients with uveitis were operated for cataract. In
      62.3% eyes (66/106), post-operative follow-up was at least 6 months. There was
      significant improvement (P < 0.001) in visual acuity after cataract surgery.
      Provided the uveitis was well controlled for three months pre-operatively,
      additional pre-operative anti-inflammatory medications did not significantly
      affect (P = 0.842) post-operative inflammation. Patients who received
      extracapsular cataract extraction (ECCE) or phacoemulsification with posterior
      chamber IOL (PCIOL) obtained better visual acuity at 6 weeks (P = 0.009 and P =
      0.032 respectively) than those with only ECCE without IOL. In 37 eyes vision did
      not improve due to persistent uveitis (23.9%, 16/67), cystoid macular oedeme
      (20.9%, 14/67), and posterior capsule opacification (14.9%, 10/67). CONCLUSION:
      Cataract extraction and PCIOL implantation is safe in eyes with uveitis.
      Additional preoperative medications may not alleviate post-operative inflammation
      if uveitis is well controlled for at least three months before surgery.

PMID- 12194566
TI  - In-vitro efficacy of antibacterials against bacterial isolates from corneal
      ulcers.
AB  - PURPOSE: To analyse the in-vitro efficacy of commonly used antibacterials against
      bacterial pathogens from corneal ulcers. METHODS: We evaluated 596 patients seen
      over 18 months, period, September 1999 through March 2001. Corneal scrapings were
      subjected to microscopy and cultures using standard protocols. Antibacterial
      susceptibility of isolated bacteria were determined by the Kirby-Bauer disc
      diffusion method. RESULTS: 626 bacterial pathogens were isolated from 596 corneal
      ulcer cases. 411(65.65%) were gram positive cocci Streptococcus pneumoniae
      (41.85%) was the predominant bacterial species. The antibacterial susceptibility
      was: 451(72.04%) to cefazolin, 471(75.24%) to chloramphenicol; 321(51.28%) to
      cephaloridine; 430(68.69%) to vancomycin; 564(90.09%) to ciprofloxacin;
      429(68.53%) to norfloxacin; 464(74.12%) to gentamicin and 202(32.27%) to
      co.trimoxazole. CONCLUSION: This study provides information on the efficacy of
      ocular antibacterials commonly used against bacterial pathogens of keratitis. It
      is hoped that this information will help decision-making in empiric initial
      treatment of bacterial keratitis.

PMID- 12194567
TI  - Clinical profile and immunological status of cytomegalovirus retinitis in organ
      transplant recipients.
AB  - PURPOSE: Cytomegalovirus retinitis (CMV) is the most common ocular opportunistic
      infection in transplant recipients. This retrospective study attempts to report
      the differences in occurrence of cytomegalovirus retinetis in transplant
      recipients from those reported in patients with acquired immunodeficiency
      syndrome (AIDS). METHODS: 25 eyes of 15 transplant recipients (14 renal and one
      cardiac) with cytomegalovirus retinitis were retrospectively reviewed.
      Immunological profile included CD4+ and CD8+ T lymphocyte counts, CD4+/CD8+ cell
      ratio (5 cases) and serology for the viral antibodies (8 cases). RESULTS: A
      predominantly bilateral presentation (60%) was noted. Active cytomegalovirus
      retinitis (72%) in zone 2 (92%) of the inferotemporal quadrant (68%) was noted.
      The average cell counts were within normal limits (mean CD4 cell count
      711/microliter), unlike in late stages of AIDS with cytomegalovirus retinitis
      (CD4 count < 50/microliter). Serology revealed an IgM positivity of 53%. Retinal
      detachment (52%) was the most common complication occurring after an average of
      5.4 months. CONCLUSION: CMV retinitis in organ transplant recipients appears to
      differ from that in AIDS patients. CMV retinitis presents early and has different
      immunological profile, probably owing to differences in pathogenesis.

PMID- 12194568
TI  - Indocyanine green enhanced maculorhexis in macular hole surgery.
AB  - PURPOSE: To demonstrate the usefulness of staining the internal limiting membrane
      (ILM) with a solution of indocyanine green (ICG) to facilitate the removal of ILM
      in eyes with idiopathic macular hole. METHODS: Eighteen patients underwent
      vitrectomy with the removal of posterior cortical vitreous, induction of
      posterior vitreous detachment (PVD), ICG-enhanced removal of the macular ILM, and
      fluid-gas exchange, followed by facedown positioning. RESULTS: Fifteen (83.33%)
      of the macular holes were closed at 3 months postoperatively. The visual outcome
      was relatively better in holes smaller than 400 microns in diameter, as compared
      to bigger macular holes (more than 400 microns in diameter). Of the 18 eyes, 9
      (50%) recorded visual improvement of 2 or more lines over the preoperative level.
      CONCLUSION: Our results show the safety and usefulness of this technique in
      visualization of the ILM during macular hole surgery, thereby leading to
      successful removal of optimal amount of ILM, with minimum damage to the retina.

PMID- 12194569
TI  - Visual field defects in non-functioning pituitary adenomas.
AB  - PURPOSE: To report the prevalence and pattern of visual field loss in non
      functioning pituitary adenomas and to study the relationship between the tumour
      size and severity of field defects. METHODS: Ninety-three patients with
      histologically confirmed pituitary adenomas, non-functional on hormonal
      assessment, underwent a complete ophthalmic assessment and automated perimetry
      using the HFA 30-2 programme. Defects with quadrantanopic or hemianopic
      characteristics, defined using criteria on the threshold/pattern deviation plots
      were considered typical. Typical defects were graded as mild, moderate and
      severe. All other defects were considered atypical. A neuroradiologist measured
      tumour size on a CT or MRI Scan. The Chi-square test for trend was used to test
      association of tumour volume with severity of typical defects. RESULTS: Eighty
      eight (94.6%) of the 93 patients had a field defect. Typical field defects were
      seen in 69 (74.2%) patients and atypical in 19 (20.4%). A severe typical defect
      involving at least 3 quadrants in one or both eyes was the most common (24
      patients or 25.80%). All 31 patients (33.3%) with a tumour size greater than 20
      cc had field defects. Severity of field defect increased with tumour volume (Chi
      square test for trends significant p = 0.0096). CONCLUSIONS: Field defects
      occurred in 95% of patients with non-functioning pituitary macroadenoma. A severe
      visual field loss involving at least 3 quadrants in one or both eyes was the most
      common. 20% of patients had atypical field defects. Severity of field defects
      increased with tumour volume.

PMID- 12194570
TI  - Argon laser suture lysis using Ritch lens following cataract surgery.
AB  - Argon laser suture lysis using the Ritch lens provides a safe and effective means
      for correction of post--ECCE suture--induced astigmatism.

PMID- 12194571
TI  - Viscoexpression of anterior chamber cysticercus cellulosae.
AB  - We report a case of anterior chamber Cysticercus cellulosae that was removed by
      viscoexpression.

PMID- 12194572
TI  - Limited Wegener's granulomatosis presenting as multiple retinal vascular
      occlusions.
AB  - In the early stages of Wegener's granulomatosis, and in the atypical forms, the
      classic clinicopathologic features of the disease are often absent, delaying
      diagnosis. Recognition of the disease and its variant is aided by serological
      markers.

PMID- 12194573
TI  - Medulloepithelioma of the ciliary body.
AB  - A rare case of medulloepithelioma of the ciliary body is described. The tumour
      necessitated enucleation of the eye; histopathological diagnosis was benign
      nonteratoid medulloepithelioma of the ciliary body.

PMID- 12194574
TI  - "String of pearls" following Nd:YAG laser posterior capsulotomy.
AB  - Posterior capsular re-opacification can occur following Nd-YAG capsulotomy. This
      necessitates multiple capsulotomies with its potential complications. We report
      one such case and discuss possible predisposing factors and preventive measures
      for this condition.

PMID- 12194575
TI  - Inverse Marcus Gunn phenomenon.
AB  - Inverse Marcus-Gunn phenomenon is very rare. It is usually acquired. We report a
      young male patient presenting with congenital ptosis and inverse Marcus-Gunn
      phenomenon.

PMID- 12194576
TI  - Population-based study of spectacles use in southern India.
AB  - This study assessed the use of spectacles and its demographic associations in a
      sample representative of the population of the Indian state of Andhra Pradesh. A
      total of 11,786 subjects of all ages were sampled from 94 clusters in one urban
      and three rural study areas of Andhra Pradesh using stratified, random, cluster,
      systematic sampling. The eligible subjects underwent detailed interview and eye
      examination including dilated examination of the posterior segment. The data on
      the use of spectacles were analysed for subjects > 15 years of age. A total of
      7,432 subjects > 15 years of age participated in the study of whom 1,030 (13.8%)
      had a refractive error of spherical equivalent +/- 3.00 Diopter or worse. The
      prevalence of current use of spectacles in those with spherical equivalent +/-
      3.00 Diopter or worse, who were likely to be visually impaired without refractive
      correction, was 34.2% (95% confidence interval 30.3-38%) and of previous use of
      spectacles was 12.3% (95% confidence interval 10.3-14.3%). The odds of using
      spectacles currently were significantly higher for those with any level of
      education, those living in the urban area, and for those with aphakia or
      psuedophakia as compared with natural refractive error. Among those who had used
      spectacles previously, 43.8% had discontinued because they felt that either the
      prescription was incorrect or that the spectacles were uncomfortable, suggesting
      poor quality of refractive services, and another 19.6% had lost the pair and
      could not afford to buy another pair. These data suggest that the use of
      spectacles in this population by those with refractive error was not optimal. Two
      thirds of those with spherical equivalent +/- 3.00 Diopter or worse were not
      using spectacles. Of those who had discontinued the use of spectacles, a
      significant proportion did so for reasons related to poor quality of refractive
      services. Strategies such as vision screening programmes and eye health promotion
      need to be implemented, the quality of refractive services monitored and the cost
      of spectacles regulated, if the substantial burden of visual impairment due to
      refractive error in this population is to be reduced.

PMID- 12194577
TI  - Anterior capsule staining. Techniques, recommendations and guidelines for
      surgeons.

PMID- 12194578
TI  - Anterior capsule staining. Techniques, recommendations and guidelines for
      surgeons.

PMID- 12194579
TI  - Problem of positioning in a patient with spinal deformities undergoing eye
      surgery.

PMID- 12194580
TI  - Supratarsal injection of corticosteroids in the treatment of refractory vernal
      keratoconjunctivitis.

PMID- 12194581
TI  - Endeavouring to improve clinical photography.

PMID- 12194582
TI  - Peer review in health sciences.

PMID- 12194583
TI  - Acquiring skills in management of HIV-related and other newer infections of the
      eye.

PMID- 12194584
TI  - Current approaches to diagnosis and management of ocular lesions in human
      immunodeficiency virus positive patients.
AB  - Human immunovirus infection in India is rapidly increasing. Ocular lesions due to
      highly active antiretroviral therapy have been well recognized. Acquired
      immunodeficiency syndrome can affect all parts of the eye. However, posterior
      segment lesions are the most common and of these, Human immunodeficiency virus
      retinopathy and cytomegalovirus retinitis predominate. Often clinical examination
      can establish the diagnosis of many ocular lesions in acquired immunodeficiency
      syndrome; therefore, ophthalmologists need to be aware of the more common ones.
      Various drugs in different routes can used to treat cytomegalovirus retinitis.
      Highly active antiretroviral therapy has remarkably reduced systemic and ocular
      morbidity among acquired immunodeficiency syndrome patients. To facilitate care
      of these patients aseptic precautions for ophthalmic care personnel are now well
      established and therefore ophthalmologist should not hesitate to provide
      ophthalmic care to acquired immunodeficiency syndrome patients.

PMID- 12194585
TI  - Primary inferior oblique overaction-management by inferior oblique recession.
AB  - PURPOSE: To evaluate the effect of 10 mm inferior oblique recession in horizontal
      strabismus with V pattern and primary inferior oblique overaction. METHODS: Ten
      patients of V esotropia and exotropia with primary inferior oblique overaction
      underwent 10 mm inferior oblique recession by the methods described by Park and
      Stallard. Pre- and postoperative V pattern, inferior oblique overaction and
      binocularity were assessed. Patients were followed up for 3 months. RESULTS: The
      mean preoperative V pattern was 38.3 PD and the mean inferior oblique overaction
      was 22 PD. After surgery the mean correction of the V pattern was 26.9 PD and the
      mean residual V pattern was 11.4 PD. None of the patients had inferior oblique
      overaction postoperatively. 70% of the patients showed improvement in
      binocularity. CONCLUSION: 10 mm Inferior oblique recession by the described
      technique is a simple, safe and effective method for the cosmetic and functional
      treatment of horizontal deviation and V pattern with primary inferior oblique
      overaction.

PMID- 12194586
TI  - [Main difficulties and advances in State sanitary and epidemiological supervision
      of occupational health in Voronezh region].
AB  - Creation of favorable work conditions necessitates gradual change-over to their
      specification on major industrial workplaces with intensive occupational hazards.

PMID- 12194587
TI  - [Physiological evaluation of work done by female hothouse workers].
AB  - The authors studied influence of work conditions and temperature mode on
      functional state of stove female workers. The results include leading factor of
      work operations, that determinates work hardiness and jeopardy class for work
      conditions. Physiologic research demonstrated changes in functional state of some
      body systems, especially cardiovascular and neuromuscular ones.

PMID- 12194588
TI  - [Effects of workplace air pollution on health of workers engaged in the
      production of nitrogen-ammonium-phosphorus fertilizers].
AB  - The authors studied work conditions in JSC "Minudobrenija" workshop for nitrogen
      phosphorus fertilizers production, revealed risk factors resulting in higher
      incidence of locomotory and respiratory diseases.

PMID- 12194589
TI  - [Complex hygienic evaluation of drivers' work conditions].
AB  - Drivers' work is characterized by various occupational hazards--higher
      psychoemotional strain associated with risk of traffic accidents, unfavorable
      microclimate, dusty and polluted air, static physical load.

PMID- 12194590
TI  - [Characteristics of work environment factors and health state of workers engaged
      in open mining of refractory clay and structural quartz sand].
AB  - This article covers evaluation of work conditions and health state in workers
      engaged into open-cast extraction of refractories and of building quartz sand in
      moderate climate of Voronezh region.

PMID- 12194591
TI  - [Evaluation of morbidity with temporary work disability in a metal treatment
      enterprise].
AB  - The authors present materials about influence of occupational factors on
      transitory disablement morbidity, exemplified by metal treatment enterprise.

PMID- 12194592
TI  - [Features of cardiovascular diseases in cleaners-up of consequences of the
      Chernobyl Nuclear Power Station accident and in residents of territories polluted
      by radionuclides].
AB  - The authors discuss features of cardiovascular diseases in liquidators of
      Chernobyl nuclear power station accident consequences and in residents of
      territories polluted with radionuclides, present recommendations on correction of
      risk factors leading to atherosclerosis--the main cause of cardiovascular
      complications.

PMID- 12194593
TI  - [Complex technogenic load and morbidity of workers engaged in synthetic rubber
      production].
AB  - Workers engaged into synthetic rubber production are exposed to multicomponent
      chemical mixtures, noise, general vibration (in excretion workshops), unfavorable
      microclimate parameters, physical and psychoemotional overload.

PMID- 12194594
TI  - [Effects of industrial processes on health of working women].
AB  - Occupational factors influence health state of working women, specific functions
      in females, pregnancy course and therefore health state of the posterity.

PMID- 12194595
TI  - [Occupational medicine in present-day furniture production].
AB  - Work conditions in furniture production are characterized by complex of
      occupational hazards: dusty and polluted air, local vibration, noise, static
      physical strain.

PMID- 12194596
TI  - [Work conditions and health of workers engaged in textile production].
AB  - Textile industry is characterized by higher share of women involved (up to 80%),
      early start of employment (since 15 years of age, with consideration of
      professional training)--that requires hygienists' special attention to the
      problem.

PMID- 12194597
TI  - [Analysis of the effectiveness of ambulatory care of atomic power station workers
      and neighboring population].

PMID- 12194598
TI  - [Organization of medical examinations of workers associated with hazardous work
      conditions (personal experience)].

PMID- 12194599
TI  - [Occupational morbidity in industrial and agricultural enterprises of Voronezh
      region].
AB  - The authors present some statistical data on occupational morbidity among workers
      engaged into various industries of Voronezh region.

PMID- 12194600
TI  - [Early diagnosis of multiple sclerosis].

PMID- 12194601
TI  - [Hygienic features of work conditions of high-load tire assemblers].

PMID- 12194603
TI  - [Hygienic features of work conditions in kinescope assembling, ways of morbidity
      prophylaxis].

PMID- 12194602
TI  - [Ways of prevention of vibration disorders].

PMID- 12194604
TI  - [Morbidity features and evaluation of health risk for galvanic shop workers].
AB  - Hygienic evaluation covered influence of occupational factors on morbidity of
      galvanic shop workers. The authors calculated the relative risk and the
      individual carcinogenic risk, defined the priority occupational diseases.

PMID- 12194605
TI  - Behavior-oriented approaches to reducing youth gun violence.
AB  - Advocacy groups on both sides of the guns issue frequently point to changing
      personal behavior--of both parents and children--as a key element in reducing gun
      violence among youth. Efforts to bring about these changes range from community
      based campaigns, to laws and programs that encourage parents to store their guns
      safely, to educational initiatives that focus on keeping young children away from
      guns and encouraging youth to resolve disputes without violence. Unfortunately,
      these behavior-oriented programs have not shown great success in reducing youth
      gun violence. This article reviews the research surrounding behavioral approaches
      to gun violence prevention and highlights obstacles that hamper the effectiveness
      of these programs. Supportive communities can play a key role in protecting youth
      from violence in general, but the few community-based violence prevention
      programs that focus on youth have not been shown to decrease youth access to or
      use of guns. By and large, behavioral programs and legal interventions aimed at
      parents have not been proven to reduce youth gun violence. This may be due in
      part to parental misperceptions about children's risk of injury and ability to
      protect themselves. Children and youth are particularly difficult targets for
      behavioral change programs. Cognitive immaturity among younger children and
      perceptions of invulnerability among adolescents may be part of the reason. Most
      programs that seek to persuade youth to stay away from guns have not been proven
      effective. The author concludes that, although behavioral programs could be
      improved, overall they hold only limited promise for reducing youth gun violence.

PMID- 12194606
TI  - Product-oriented approaches to reducing youth gun violence.
AB  - Injury prevention experts have suggested that gun manufacturers could reduce
      youth violence by changing the design of guns. Product safety features could make
      guns more difficult for children to fire unintentionally and more difficult to
      use if stolen or obtained illegally. This article gives a brief history of
      efforts to make safer, smarter guns and assesses the potential of the product
      safety approach for reducing youth gun violence. Among the article's key
      findings: Research from the injury prevention field suggests that changing
      product design may be more effective in preventing injuries than trying to change
      personal behaviors; Existing product safety technologies for guns could reduce
      unintentional gun injuries, especially to young children. In addition, emerging
      technologies will enable gun manufacturers to "personalize" guns, which could
      prevent unauthorized users of any age from firing the weapons. Personalization
      could decrease access to guns by adolescents; Gun manufacturers have been slow to
      incorporate safety features into their products; but legislative, regulatory, and
      litigation efforts are under way to mandate safer guns. The authors envision a
      future when the law requires product safety features--including personalization-
      on all new firearms. These product safety features have the potential to reduce
      both intentional and unintentional firearm injury and death.

PMID- 12194607
TI  - Policing guns and youth violence.
AB  - To combat the epidemic of youth gun violence in the 1980s and 1990s, law
      enforcement agencies across the United States adopted a variety of innovative
      strategies. This article presents case studies of eight cities' efforts to police
      gun crime. Some cities emphasized police-citizen partnerships to address youth
      violence, whereas others focused on aggressive enforcement against youth
      suspected of even minor criminal activity. Still others attempted to change youth
      behavior through "soft" strategies built on alternatives to arrest. Finally, some
      cities used a combination of approaches. Key findings discussed in this article
      include: Law enforcement agencies that emphasized police-citizen cooperation
      benefited from a more positive image and sense of legitimacy in the community,
      which may have enhanced their efforts to fight crime. Aggressive law enforcement
      strategies may have contributed to a decline in youth gun violence, but they also
      may have cost police legitimacy in minority communities where residents felt that
      the tactics were unfair or racially motivated. Approaches that emphasize
      nonarrest alternatives and problem-solving strategies offer an intriguing but
      unproven vision for addressing youth gun violence. None of the initiatives
      presented in the case studies has been shown conclusively to reduce youth gun
      crime over the long term. The author suggests that policing alone cannot contain
      youth gun violence, but by carefully balancing enforcement with community
      collaboration, police departments can help shift social norms that contribute to
      youth gun violence.

PMID- 12194608
TI  - Public opinion about gun policies.

PMID- 12194609
TI  - Children and guns: advocacy groups speak out.

PMID- 12194610
TI  - Firearm-related death and injury among children and adolescents.
AB  - As the articles in this journal issue show, gun violence affects children and
      youth in many ways: psychologically, emotionally, financially, and legally. But
      first and foremost, gun violence affects children's physical safety. Therefore,
      this issue opens with an overview of the physical toll that firearms exact upon
      children and youth, reviewing the incidence of firearm-related injury and death
      among Americans under age 20. This article analyzes trends and current status in
      firearm death and injury, based on nationwide data collected by the federal
      government. Several key findings emerge from the data: Firearm death rates among
      children and youth in the United States have declined dramatically since 1993,
      but remain high compared with historical rates in this country and rates in other
      developed nations. A majority of these deaths are homicides. Certain groups of
      children and youth, especially adolescents, boys, minority youth, and those
      residing outside the Northeast, are particularly at risk for firearm death. The
      problem is most acute among black teenage males. Firearm injuries are much more
      likely to result in death than are other injuries for which children and youth
      visit emergency departments--a reflection of the extreme lethality of firearms.
      Given these findings, the authors call for a concerted effort to reduce youth
      firearm deaths to levels comparable to those of other industrialized nations,
      using a wide variety of approaches that span the public health, criminal justice,
      and educational spheres. They also recommend improved data systems to track
      firearm injury and death, so that researchers can better analyze these incidents
      and evaluate intervention strategies.

PMID- 12194611
TI  - Youth, guns, and violent crime.
AB  - Young people are overrepresented as both victims and perpetrators of violence.
      Indeed, some commentators have suggested that recent cohorts of youth have been
      composed of "superpredators" who have little regard for human life. The evidence,
      however, suggests that other factors are responsible for recent increases in
      youth gun violence. This article analyzes the extent and causes of youth violence
      in the United States, paying particular attention to the late 1980s and early
      1990s, when rates of homicide and robbery committed by youth rose to extremely
      high levels. Examination of trends for these crimes shows that: The increase in
      violence in the United States during the late 1980s and early 1990s was due
      primarily to an increase in violent acts committed by people under age 20.
      Similarly, dramatic declines in homicide and robbery in recent years are
      attributable primarily to a decline in youth violence. The increase in youth
      homicide was predominantly due to a significant increase in the use of handguns,
      which converted ordinary teenage fights and other violent encounters into
      homicides. Several other interrelated factors also fueled the rise in youth
      violence, including the rise of illegal drug markets, particularly for crack
      cocaine, the recruitment of youth into those markets, and an increase in gun
      carrying among young people. The author points out that youth violence diminished
      as the crack markets shrank, law enforcement increased efforts to control youth
      access to guns, youth gun carrying declined, and the robust economy provided
      legitimate jobs for young people.

PMID- 12194612
TI  - Children, youth, and gun violence: analysis and recommendations.

PMID- 12194614
TI  - Mitigating the effects of gun violence on children and youth.
AB  - Countless children and youth are exposed to gun violence each year--at home, at
      school, in their communities, or through the media. Gun violence can leave
      lasting emotional scars on these children. This article reviews research
      regarding the psychological effects of gun violence on children and youth, and
      offers suggestions for how parents, school administrators, and mental health
      workers can mitigate these negative effects. Children exposed to gun violence may
      experience negative short- and long-term psychological effects, including anger,
      withdrawal, posttraumatic stress, and desensitization to violence. All of these
      outcomes can feed into a continuing cycle of violence. Certain children may be at
      higher risk for negative outcomes if they are exposed to gun violence. Groups at
      risk include children injured in gun violence, those who witness violent acts at
      close proximity, those exposed to high levels of violence in their communities or
      schools, and those exposed to violent media. Parents, school administrators, and
      mental health workers all can play key roles in protecting children from gun
      violence and helping them overcome the effects of gun-related trauma. The authors
      recommend a number of strategies that adults can adopt to help children cope with
      gun violence, such as increasing parental monitoring, targeting services to youth
      at risk of violent activity, and developing therapeutic interventions to help
      traumatized young people.

PMID- 12194615
TI  - The costs of gun violence against children.
AB  - Gun violence imposes significant costs on children, families, and American
      society as a whole. But these costs can be difficult to quantify, as much of the
      burden of gun violence results from intangible concerns about injury and death.
      This article explores several methods for estimating the costs of gun violence.
      One method is to assess how much Americans would be willing to pay to reduce the
      risk of gun violence. The authors use this "willingness-to-pay" framework to
      estimate the total costs of gun violence. Their approach yields the following
      lessons: Although gun violence has a disproportionate impact on the poor, it
      imposes costs on the entire socioeconomic spectrum through increased taxes,
      decreased property values, limits on choices of where to live and visit, and
      safety concerns. Most of the costs of gun violence--especially violence against
      children--result from concerns about safety. These are not captured by the
      traditional public health approach to estimating costs, which focuses on medical
      expenses and lost earnings. When people in a national survey were asked about
      their willingness to pay for reductions in gun violence, their answers suggested
      that the costs of gun violence are approximately $100 billion per year, of which
      at least $15 billion is directly attributable to gun violence against youth. The
      authors note that in light of the substantial costs of gun violence, even
      modestly effective regulatory and other interventions may generate benefits to
      society that exceed costs.

PMID- 12194613
TI  - Where the guns come from: the gun industry and gun commerce.
AB  - Under federal law, it is illegal for youth under age 18 to purchase rifles or
      shotguns, and for those under age 21 to purchase handguns. However, fatality and
      injury statistics clearly show that guns are finding their way into young
      people's hands. Many of these youth obtain guns through illegal gun markets. This
      article focuses on how guns in the United States are manufactured, marketed, and
      sold. The article shows how the legal and illegal gun markets are intimately
      connected and make guns easily accessible to youth. Although the domestic gun
      manufacturing industry is relatively small and has experienced declining sales in
      recent years, it has significant political clout and a large market for its
      products, and has engaged in aggressive marketing to youth. Lax oversight of
      licensed firearms dealers, combined with little or no regulation of private sales
      between gun owners, mean that guns can quickly moved from the legal gun market
      into the illegal market, where they can be acquired by young people. Certain
      guns, especially inexpensive, poorly made small handguns, are particularly
      attractive to criminals and youth. The author observes that several policy
      innovations--including increased regulation of licensed firearms dealers,
      intensified screening of prospective buyers, regulation of private sales, gun
      licensing and registration, and bans on some types of weapons--hold promise for
      decreasing the flow of guns into the hands of youth.

PMID- 12194616
TI  - Children, youth and gun violence. Selected bibliography.

PMID- 12194617
TI  - Sensory stimulation of brain-injured individuals in coma or vegetative state:
      results of a Cochrane systematic review.
AB  - OBJECTIVES: To assess the effectiveness of sensory stimulation programmes in
      patients in coma or vegetative state. DESIGN: Systematic review of randomized
      control trials (RCT) and nonrandomized controlled clinical trials (CCT) comparing
      any type of stimulation programmes with standard rehabilitation in patients in
      coma or vegetative state. The Injuries Group specialized register, the Cochrane
      Controlled trial register, EMBASE, MEDLINE, CINAHL, PSYCHLIT from 1966 to January
      2002 were searched without language restriction. Reference lists of articles were
      scanned and experts in the area contacted to find other relevant studies.
      Abstracts and papers found were initially screened by one reviewer. Three
      reviewers independently identified relevant studies, extracted data and assessed
      study quality, resolving disagreement by consensus. OUTCOME MEASURES: Duration of
      unconsciousness (including coma and vegetative state) defined as the time between
      trauma and objective recovery of the ability to respond to verbal commands; level
      of consciousness, as measured by the Glasgow Coma Scale (GCS); level of cognitive
      functioning (LCF); functional outcomes, as measured by Glasgow Outcome Scale
      (GOS) or by Disability Rating Scale; negative effects (e.g. increased
      intracranial pressure). RESULTS: Three studies (one RCT and two CCTs) with 68
      traumatic brain-injured patients in total, most of whom were road accident
      victims, met the inclusion criteria. The overall methodological quality was poor
      and studies differed widely in terms of study design and conduct. Moreover, due
      to the diversity in reporting of outcome measures, a quantitative metanalysis was
      not possible. None of the three studies provided useful and valid results on
      outcomes of clinical relevance for coma patients. CONCLUSIONS: This systematic
      review indicates that there is no reliable evidence to support the effectiveness
      of multisensory stimulation programmes in patients in coma or the vegetative
      state.

PMID- 12194619
TI  - A randomized controlled trial of the effects of weights on amplitude and
      frequency of postural hand tremor in people with Parkinson's disease.
AB  - OBJECTIVE: To evaluate the effects of weights on postural hand tremor related to
      self-feeding in subjects with Parkinson's disease (PD). DESIGN: In a repeated
      measures design, postural hand tremor was recorded three times in each of three
      weight conditions in a single session for each subject. The order of all
      recording conditions was randomized. SETTING: Intervention was applied and
      measurement was conducted in a university-based motor performance laboratory.
      SUBJECTS: Fourteen men and two women diagnosed with PD and having hand tremor
      participated (mean age 67.1 years, mean duration of PD 4.6 years). All were
      community-dwelling. INTERVENTION: The control condition consisted of holding a
      built-up spoon (108 g). There were two experimental conditions: holding a
      weighted spoon (248 g); and holding the built-up spoon while wearing a weighted
      wrist cuff (470 g). MAIN OUTCOME MEASURES: Three measures of tremor amplitude and
      two measures of tremor frequency were calculated from recordings of displacement
      of the spoon obtained from laser displacement sensors. RESULTS: Repeated-measures
      analyses of variance revealed no significant differences across conditions in any
      measure of tremor amplitude or in either measure of tremor frequency.
      Correlational and Mann-Whitney U-test analyses revealed that none of age, disease
      duration or medication intake had any significant relationship with tremor
      amplitude in the control condition or with whether amplitude was altered by
      weights. CONCLUSIONS: The findings suggest that there is no support for the
      clinical recommendation of using weighted utensils or weighted wrist cuffs to
      alleviate postural hand tremor in PD.

PMID- 12194618
TI  - The effect of independent practice of motor tasks by stroke patients: a pilot
      randomized controlled trial.
AB  - OBJECTIVE: To investigate the effect of independent practice of sitting balance
      as an addition to standard physiotherapy treatment for patients with stroke.
      DESIGN: Randomized controlled trial, using blocked randomization procedure with
      2:1 ratio. SUBJECTS: Inpatients with diagnosis of stroke, having achieved one
      minute of independent sitting balance but not yet achieved 10 independent steps,
      and with no known previous disabilities, pathology or neurological deficit
      affecting mobility prior to stroke. INTERVENTION: A four-week regime of
      independent practice aimed at improving aspects of balance, as an addition to
      standard physiotherapy treatment based on the Bobath Approach. MAIN OUTCOME
      MEASURE: Proportion of patients achieving 'normal' symmetry of weight
      distribution during sitting, standing, rising to stand, sitting down, and
      reaching. RESULTS: Nineteen subjects were randomized to the control group; nine
      to the intervention group. There were no clinically significant differences in
      measured outcome between the groups. CONCLUSIONS: The regime of independent
      practice had no measured beneficial effect on the balance ability of patients
      with recently acquired stroke.

PMID- 12194620
TI  - Performance of a mail-administered version of a stroke-specific outcome measure,
      the Stroke Impact Scale.
AB  - OBJECTIVE: To evaluate the feasibility and concurrent validity of a new, mail
      administered, stroke-specific outcome measure, the Stroke Impact Scale (SIS).
      DESIGN: Observational cohort study. SETTING AND PATIENTS: Stroke patients who had
      lived independently in the community prior to their stroke and who were
      candidates for post-stroke rehabilitation were recruited from nine, high-volume,
      Department of Veteran Affairs Medical Centers. METHODS: Two hundred and six
      patients were mailed the SIS after a six-month post-stroke telephone interview.
      Telephone assessments included the Functional Independence Measure, the Lawton
      IADL and the SF-36. RESULTS: The response rate for the mailed SIS was 63%, with
      45% of the responses from proxies. The average rate of missing item level scores
      per patient was 1.3 (range 0-20) resulting in an average rate of 0.13 missing
      domain scores per patient (range 0-3). Nonresponders to the mailed SIS had more
      severe strokes with lower functional status at the time of the survey than
      responders. Proxies were more likely to complete the survey if the subjects were
      older, married, cognitively impaired and more functionally limited. The SIS did
      not exhibit a high rate of floor and ceiling effects, particularly in physical
      function domains, as did the FIM and the SF-36. CONCLUSIONS: The mailed SIS is a
      feasible means of assessing post-stroke function. Missing items and missing
      domain scores were extremely low, however, there is a trade-off between the low
      cost mail SIS survey on the one hand and the resulting nonresponse bias on the
      other.

PMID- 12194621
TI  - Spouses of first-ever stroke patients: their view of the future during the first
      phase after stroke.
AB  - BACKGROUND: A partner's stroke can be perceived as a critical event by a spouse.
      Previous studies have focused primarily on the impact of stroke on spouses'
      psychosocial well-being over the long term. However, the experience of spouses in
      the first phase after stroke is not well known. AIM: To investigate spouses'
      perception of their future daily life after stroke and the association between
      this perception and the objective characteristics of the stroke. METHOD: Eighty
      three consecutively enrolled spouses of first-ever stroke patients < 75 years
      admitted to Sahlgrenska University Hospital in Goteborg, Sweden participated. The
      mean age of the spouses was 57 years. Sixty-two of the spouses were women and 21
      men. Interviews about their experiences 10 days after onset were generally made
      at the hospital. The interviews were analysed, categorized and combined with
      statistical analyses of variables such as ages and sex of the spouses, type of
      lesion and presence of neurological impairments in the stroke patient. RESULTS:
      Four different categories of the concept 'view of the future' were developed on
      the basis of the interviews. Of the different characteristics of the stroke, the
      severity of the sensorimotor impairment seemed to have the greatest impact on the
      spouses' view of the future. The spouses of stroke patients with pure
      sensorimotor impairment were more likely to have an optimistic view of the future
      than when the sensorimotor impairment was combined with cognitive deficits. There
      was a broad distribution of the different characteristics of stroke between the
      four categories. CONCLUSIONS: Although the perception of future daily life
      varied, it was possible to categorize the spouses' cognitive image of future life
      according to degree of optimism. While the severity of stroke was of importance,
      the individual perception of the disease, impact on future activities and the
      spouses' own coping capacity was of great significance for the perception of
      future daily life.

PMID- 12194623
TI  - The Rivermead Assessment of Somatosensory Performance (RASP): standardization and
      reliability data.
AB  - OBJECTIVE: To develop a standardized, clinically relevant, quantitative
      assessment of somatosensory performance in patients with stroke. DESIGN:
      Prospective observational study and test evaluation. SETTING: Local Oxford
      hospitals and a regional neurological rehabilitation centre. SUBJECTS: Stroke
      patients with a first, lateralized acute stroke in hospital, and age-matched
      control subjects. METHOD: Each patient was assessed in a structured way using a
      new battery of formal tests of somatosensory performance. RESULTS: A total of 100
      patients and 50 controls were fully investigated. Control subjects performed at
      or near ceiling on all tests, but patients showed impaired performance on all
      tests. The Rivermead Assessment of Somatosensory Performance (RASP) showed good
      intra-rater and inter-rater reliability for all subtests. There were however only
      weak relationships between scores of sensory impairment and scores of motor
      impairment or mobility and dependence. CONCLUSIONS: The RASP provides a practical
      and reliable assessment of sensory loss, which provides the clinician with a
      comprehensive picture of the patient's performance and can be used to inform and
      monitor rehabilitation and recovery.

PMID- 12194622
TI  - Prevalence of spasticity post stroke.
AB  - OBJECTIVES: To establish the prevalence of spasticity 12 months after stroke and
      examine its relationship with functional ability. DESIGN: A cohort study of
      prevalence of spasticity at 12 months post stroke. SETTING: Initially
      hospitalized but subsequently community-dwelling stroke survivors in Liverpool,
      UK. SUBJECTS: One hundred and six consecutively presenting stroke patients
      surviving to 12 months. MAIN OUTCOME MEASURES: Muscle tone measured at the elbow
      using the Modified Ashworth Scale and at several joints, in the arms and legs,
      using the Tone Assessment Scale; functional ability using the modified Barthel
      Index. RESULTS: Increased muscle tone (spasticity) was present in 29 (27%) and 38
      (36%) of the 106 patients when measured using the Modified Ashworth Scale and
      Tone Assessment Scale respectively. Combining the results from both scales
      produced a prevalence of 40 (38%). Those with spasticity had significantly lower
      Barthel scores at 12 months (p < 0.0001). CONCLUSION: When estimating the
      prevalence of spasticity it is essential to assess both arms and legs, using both
      scales. Despite measuring tone at several joints, spasticity was demonstrated in
      only 40 (38%) patients, lower than previous estimates.

PMID- 12194624
TI  - A completed audit cycle and integrated care pathway for the management of
      depression following brain injury in a rehabilitation setting.
AB  - OBJECTIVE: To develop an evidence-based multidisciplinary integrated care pathway
      (ICP) for the management of depression following brain injury in a rehabilitation
      setting, and to assess its impact on standards of care and documentation.
      SETTING: A regional rehabilitation unit providing inpatient rehabilitation for
      young patients (16-65) with complex disabilities mainly resulting from brain
      injury. METHODS AND DESIGN: A completed cycle of audit including: standards set
      for documentation, assessment, management and review; an initial retrospective
      audit of documented patient management against those standards during a five-year
      period (26 patient records); ICP development by a multidisciplinary team of
      doctors, psychologists and nurses based on clinical opinion and systematic review
      of the literature; re-audit from the ICP documentation (48 patient records) over
      a period of 15 months. RESULTS: The initial audit demonstrated borderline
      acceptable documentation of baseline mood state and start of medication (54-61%),
      but poor documentation of review (29%) and subsequent treatment (27%).
      Introduction of the ICP improved all standards of documentation to 94-100%,
      except for assessment using a validated measure (84%) and follow-up assessment
      (76%). CONCLUSIONS: This ICP raised staff awareness of depression, leading to
      improved documentation and possibly also standards of care.

PMID- 12194625
TI  - Factors associated with cardiac rehabilitation attendance: a systematic review of
      the literature.
AB  - BACKGROUND: Many eligible patients fail to attend cardiac rehabilitation courses.
      OBJECTIVE: To undertake a systematic literature review of studies that have
      investigated factors associated with cardiac rehabilitation attendance. METHODS:
      Literature published between 1978 and 2001 was searched using the MEDLINE,
      PSYCINFO and CINAHL computerized databases. Studies were sought that examined
      course attendance in eligible patient samples. Studies had to include at least
      one baseline predictor variable. RESULTS: Fifteen studies were identified and
      predictor variables were usually categorized as sociodemographic, medical and
      psychological. Nonattenders are more likely to be older, to have lower
      income/greater deprivation, to deny the severity of their illness; they are less
      likely to believe they can influence its outcome or to perceive that their
      physician recommends cardiac rehabilitation. Job status, gender and health
      concerns play an indirect role in attendance behaviour. Comparison of results
      between studies could be influenced by different case-mix, measurement
      instruments and country of origin. CONCLUSION: A number of factors predict
      cardiac rehabilitation attendance and some of these are potentially modifiable.

PMID- 12194626
TI  - A randomized, controlled comparison of home versus institutional rehabilitation
      of patients with hip fracture.
AB  - OBJECTIVE: To compare ambulation outcomes between home and institutional
      rehabilitation of patients with hip fracture. DESIGN: Randomized controlled
      clinical equivalence trial. SETTING: The Queen Elizabeth Hospital in Hong Kong.
      SUBJECTS: Eighty-one patients with hip fracture. INTERVENTION: Study group
      patients (40) were discharged directly home from the acute hospital and visited
      by a physiotherapist an average of 4.6 times. The control group subjects (41)
      were discharged to a rehabilitation centre for further treatment lasting on
      average 36.2 days (SD 14.6) and they received physiotherapy daily. MAIN OUTCOME
      MEASURES: Ambulation ability measured on a categorical scale. RESULTS: The mean
      age of the subjects was 75 years (SD 8.3 years). Females comprised 60% of all the
      subjects and majority were retired or home makers. Both groups of patients
      improved in their ambulation ability during their rehabilitation period but
      neither group achieved their pre-ambulatory status by the time of completion of
      the study. The study group achieved significantly higher ambulation scores (p <
      0.05) for community and household ambulation compared with the control group by
      the end of the study, a year after operation. CONCLUSION: Five visits by a
      physiotherapist in the patient's home after discharge from an acute hospital
      after surgical treatment for hip fracture yielded better results in ambulation
      ability than one month of conventional institution-based rehabilitation.

PMID- 12194628
TI  - Cognitive assessment and neurological rehabilitation.

PMID- 12194627
TI  - A study to compare the reliability of composite finger flexion with goniometry
      for measurement of range of motion in the hand.
AB  - OBJECTIVE: To establish the intra- and inter-rater reliability of composite
      finger flexion (CFF), and to compare this with goniometry. DESIGN: Fifty-one
      physiotherapists and occupational therapists took part in the study. The hand of
      a normal subject was splinted in three different positions. Using a goniometer
      and a ruler alternately, each therapist measured both the proximal
      interphalangeal joint and CFF of three digits, following a standardized protocol.
      This process was repeated three times. SETTING: Eighteen NHS hospital sites in
      the UK. RESULTS: The two measurement methods produced different ranges and
      standard deviations for each digit. The repeatability coefficient shows that
      repeated intra-rater goniometric measures fall within 4-5 degrees of each other
      95% of the time. Inter-rater goniometric measures fall within 7-9 degrees.
      Repeated intra-rater CFF measures fall within 5-6 mm of each other, whereas inter
      rater fall within 7-9 mm. The influence of occupation, experience in hand
      therapy, years of practice and routine use were found to have no effect on
      reliability. Scaling of the two methods of measurement allowed comparison between
      them to be made. CFF and goniometry are equally reliable when comparing inter
      rater reliability, but goniometry displays less variability than composite finger
      flexion for intra-rater measurements. CONCLUSION: In this study involving a
      subject with normal joints, goniometry is more reliable than CFF when only one
      measurer is involved. However, CFF may be a useful alternative where multiple
      joint measures are required, or when goniometry is impracticable.

PMID- 12194629
TI  - Effect of deep inhalations after a bronchial methacholine provocation in
      asthmatic and non-asthmatic subjects.
AB  - Deep inhalations cause a transient relaxation of the peripheral airways smooth
      muscles in non-asthmatic subjects. It has been claimed that the airway response
      to deep inhalations may be different in asthmatic subjects in whom deep
      inhalations should rather cause bronchoconstriction. The aim of the present study
      was to find out whether deep inhalations discriminate between asthmatic and non
      asthmatic subjects with pre-constricted airways, using a methacholine provocation
      test protocol with deep inhalations following the last dose of methacholine. In
      164 adults, a methacholine provocation was performed. Directly after the FEV1
      measurement at the highest metacholine concentration, the subjects took one deep
      breath and another three deep inhalations 20 s later. One minute after the
      inhalation of the highest concentration FEV1 was measured twice. Thirty-three
      asthmatics PD20FEV1 = 0.24 mg (0.13-0.39) (median, 25-75th 75th percentiles) and
      131 non-asthmatics PD20FEV1 = 2.05 mg (0.72-10.1) participated. The mean maximal
      decrease in FEV1 after the provocation test was 36% in the asthmatics and 27% in
      the non-asthmatics. Corresponding values after the deep inhalations were 18% in
      the asthmatics and 12% in the non-asthmatics. In conclusion, deep inhalations
      attenuate the methacholine-induced bronchoconstriction in both asthmatic and non
      asthmatic subjects. Thus, the effect of deep inhalations did not discriminate
      between asthmatic and non-asthmatic subjects.

PMID- 12194630
TI  - Safety of sputum induction in moderate-to-severe chronic obstructive pulmonary
      disease.
AB  - This retrospective study was designed to evaluate the safety and efficacy of a
      bronchoprotective sputum induction protocol in moderate to severe chronic
      obstructive pulmonary disease (COPD). Forty-two adults with COPD (FEV1 = 51.7 +/-
      3.2% predicted (mean +/- SEM)) under went sputum induction using a protocol
      designed to minimize hypertonic saline-induced bronchoconstriction. Hypertonic
      (3%) saline was used for subjects with FEV1 > or = 50%, and normal (0.9%) saline
      was used for subjects with FEV1 < 50%. Primary outcomes were change in peak flow,
      FEV1 and oxygen saturation. Mean decline in peak flow during sputum induction was
      13.2 +/- 2.1%. FEV1 fell by 11.4 +/- 2.3%, an absolute fall of 0.14 +/- 0.031.
      Oxygen saturation did not change. A fall in peak flow of > or = 20% reliably
      predicted a fall in FEV1 of > or = 20%. Thirty-five of 42 subjects (83.3%)
      produced an acceptable sputum sample. Sputum eosinophil and neutrophil
      percentages were 2.8 +/- 0.9 and 73.0 +/- 3.0%, respectively, and were not
      correlated with changes in peak flow, FEV1 or oxygen saturation. A protocol for
      sputum induction which restricts the use of hypertonic saline based on lung
      function is both safe and effective in subjects with moderate to severe COPD.

PMID- 12194631
TI  - Pulmonary diffusing capacity in chronic dialysis patients.
AB  - Patients with end-stage renal disease treated by hemodialysis with
      bioincompatible membranes are exposed during the dialysis period to acute effects
      on lung microcirculation, which may result in pulmonary fibrosis and diffusion
      defects in long-standing dialysis. To investigate the occurrence of these
      possible chronic pulmonary alterations, we determined lung function in patients
      with chronic renal failure not undergoing hemodialysis and in patients who had
      been receiving regular hemodialysis both for short and long periods of time.
      Forty-three patients divided into three groups were studied: 17 patients before
      dialysis with a mean (SD) creatinine clearance of 14.1 (6.8) ml/min 11.73 m2, 10
      patients receiving regular hemodialysis for a period of less than 12 months (mean
      6.4 +/- 3.5 months), and 16 patients receiving regular hemodialysis for more than
      5 years (mean 8.3 +/- 3.6 years). First-use bioincompatible cellulosic dialysis
      membranes were used in all the cases. The following parameters were recorded:
      forced vital capacity (FVC), forced expiratory volume in 1s (FEV1), total lung
      capacity (TLC), residual volume (RV), carbon monoxide transfer factor (TLCO),
      accessible lung volume (VA), carbon monoxide transfer factor/accessible lung
      volume (KCO- that is, TLCO/VA), and arterial blood gases. Patients receiving
      regular hemodialysis for more than 5 years showed significantly lower values of
      TLCO and KCO than patients before dialysis and patients receiving regular
      hemodialysis for less than 12 months. Seventy-five percent of patients on long
      term hemodialysis had markedly reduced TLCO or KCO values (below 80% of the
      reference value) as compared with 17% of patients before dialysis and 10% of
      patients dialyzed for less than 12 months (P < 0.001). Differences among groups
      for the remaining parameters were not observed. In conclusion, patients
      undergoing long-term regular hemodialysis with a bioincompatible membrane showed
      a selective reduction in pulmonary diffusing capacity possibly due to chronic
      pulmonary fibrosis.

PMID- 12194632
TI  - Bronchodilating effects of salbutamol from a novel inhaler Airmax.
AB  - This randomized, placebo-controlled, evaluator-blind, five-way crossover study
      compared the equivalence in terms of FEV1 response to single ascending cumulative
      doses of salbutamol (100-400 micrograms) from Airmax, a new multidose dry powder
      inhaler, in comparison with placebo, the same dose from a standard pressurized
      metered dose inhaler (Ventolin) or at double the dose from the dry powder
      inhalers Diskhaler and Accuhaler. Sixty-one adult asthmatic subjects with FEV150
      80% predicted and > or = 15% increase in FEV1 to salbutamol took part.
      Equivalence was declared if the 95% CI for the ratio of the FEV1 responses to the
      two treatments was within the range 90-111%. Following the cumulative four doses,
      FEV1 (1) changes pre-dose to the highest dose were: 2.53-3.31, 2.47-3.30, 2.51
      3.35, 2.52-3.31 and 2.57-2.55 for Airmax salbutamol, salbutamol Ventolin,
      salbutamol Diskhaler, salbutamol Accuhaler and placebo, respectively. The 95% CIs
      for the ratio of Airmax salbutamol to each of the active devices were within +/-
      5% demonstrating a 1:1 dose equivalence between Airmax salbutamol and Ventolin
      and a 1:2 dose equivalence between each of the other two salbutamol dry powder
      devices. Adverse events profiles were similar for all treatments. In conclusion,
      the novel multidose inhaler Airmax salbutamol is as efficacious and safe as the
      pressurized metered dose inhaler without the need for co-ordinating actuation and
      inhalation and with the added benefit of a dose counter.

PMID- 12194633
TI  - Evaluation of the end-expiratory pressure by multiple linear regression and
      Fourier analysis in humans.
AB  - This study was designed to compare the end-expiratory pressure (EEP) during
      mechanical ventilation (MV) measured dynamically (EEPdyn), by multiple linear
      regression (MLR) of the airway pressure (Pao) vs volume (V) and flow (V') and
      after Fourier analysis (FA) of the Pao and V'. Pao and V' were recorded from 32
      ICU patients (II without respiratory disease, 10 COPD, II ARDS) under MV, at
      three levels of PEEPe (0, 5 and 10 hPa). Volume was calculated by numerical
      integration of V'. Data were analysed by MLR and FA, while the actual value of
      EEPdyn was recognised on the Pao signal at zero V' and V. EEPdyn, EEPMLR and
      EEPFA were compared for all patients, for each group of patients and for every
      level of applied PEEPe. Despite the different evaluation of respiratory mechanics
      between MLR and FA, the EEP values were always not significantly different
      between the three applied methods (P > 0.05). A high degree of correlation was
      found between them, taken two at a time (r > 0.99, P < 0.001). Two non-invasive
      analytical methods for the evaluation of respiratory mechanics during MV, MLR and
      FA offer a reliable and clinically useful estimation of EEP during MV.

PMID- 12194634
TI  - Risk of tuberculosis among healthcare workers: can tuberculosis be considered as
      an occupational disease?
AB  - This study aimed to determine the incidence of tuberculosis among hospital
      employees in four major urban institutions, which employ nearly 90% of all
      hospital workers caring for adult patients in a city of 2.5 million inhabitants.
      It also had the objective of finding out whether this incidence changes according
      to the in-hospital setting, i.e. the departments, and thus, whether tuberculosis
      can be considered to pose an occupational risk. The study population consisted of
      all healthcare workers of the four hospitals between 1986 and 1998. From these,
      those who developed tuberculosis within this period were determined and were
      considered as the case group. All the remaining employees constituted the control
      group. Fifty-nine healthcare workers were found to have developed the disease.
      The annual incidence was found to range between 0.016 and 0.139%. Tuberculosis
      was seen 3 times more frequently among the hospital employees than the general
      population. The workers in departments of chest diseases were found to have a
      higher risk than those of other departments (OR: 6.37, CI: 3.69-11.00).
      Similarly, the nurses were also at a higher risk than the doctors (OR: 2.63, CI:
      1.12-6.36). These findings suggest that tuberculosis can be considered as an
      occupational disease.

PMID- 12194636
TI  - The frequency of deep venous thrombosis and pulmonary embolus in acute
      exacerbation of chronic obstructive pulmonary disease.
AB  - Infection, pulmonary embolism caused by mostly deep venous thrombosis (DVT),
      hypoxaemia and drugs, used in the treatment of chronic obstructive pulmonary
      disease (COPD), related arrhythmia, aspiration are mostly responsible for acute
      exacerbations of COPD. The incidences of DVT and pulmonary embolus were
      investigated in 56 hospitalised cases with acute exacerbation of COPD. DVT was
      diagnosed in six (10.7%) cases with coloured doppler ultrasonography (CDU) and in
      two cases whose examinations were not sufficient enough to diagnose or refuse
      DVT. Diagnosis of pulmonary embolus was investigated with ventilation/perfusion
      scintigraphy in eight cases of clinically medium--high-probable pulmonary
      embolus. Pulmonary embolus was determined in five cases (8.9%). Age, weight,
      height, disease course, pulmonary function tests, arterial blood gases and
      haematocrit values of the cases did not predict the diagnosis of DVT and
      pulmonary embolus in our cases.

PMID- 12194635
TI  - Do steroids interfere in dyspnoea sensation?
AB  - Dyspnoea remains a remarkable clinical problem and a therapeutic challenge,
      mainly in chronic respiratory conditions. This study investigated the potential
      effects of steroids on dyspnoea sensation regardless of their pulmonary anti
      inflammatory actions. Sixteen healthy men (mean age +/- SD = 22.5 +/- 1.6 years)
      developed uncomfortable breathing by the use of inspiratory resistors (loads of
      0, 7, 14 and 21 cm H2O/l/s) and breathholding 6 h after taking 40 mg of
      prednisone (Pred) or placebo (Plac). Respiratory discomfort during breathing with
      loads was evaluated with a 100 mm visual analog scale. The maximum voluntary
      apnoea time did not differ between the prednisone and placebo days (Plac = 96 +/-
      11.8 s x Pred = 105 +/- 12.2 s) and prednisone did not influence the dyspnoea
      sensation induced by different inspiratory loads (0 cm H2O/l/s: Pred = 2.8 mm x
      Plac = 1.9 mm; 7 cm H2O/l/s: Pred = 18.3 mm x Plac = 18.6 mm; 14 cm H2O/l/s; Pred
      = 33.0 mm x Plac = 34.1 mm; 21 cm H2O/l/s: Pred = 48.1 mm x Plac = 49.6 mm).
      Prednisone intake was associated with a significant increase in minute
      ventilation during breathing with no inspiratory loads (Pred = 11.91 +/- 1.28
      l/min- x Plac = 9.95 +/- 0.86 l/min). Although steroids certainly may improve
      respiratory conditions due to anti-inflammatory actions, available evidence does
      not support any specific beneficial effect of these drugs on these perception of
      dyspnoea itself.

PMID- 12194637
TI  - Evaluation of long-term efficacy of an asthma education programme in an out
      patient clinic.
AB  - The aim of the present study was to evaluate long-term efficacy of a patient
      education programme in an asthma out-patient clinic. The study included two
      groups. Educational group consisted of 25 patients who were given special
      education for one year. Usual care group included 27 patients who were not given
      special education. All patients were evaluated after 3 years follow-up period.
      Mean per cent asthma knowledge score (KS%), mean per cent demonstration score
      (DS%), daytime and nighttime symptom scores, Aas score, and pulmonary function
      tests were measured. The asthma-quality-of-life assessment was performed. The
      rate of application to emergency room and admission to hospital for last 1 year
      had been calculated. KS% was higher in educational group than in usual care group
      (P < 0.001). Daytime score was 0.3 +/- 0.6 in educational group and was 0.8 +/-
      1.2 in usual care group (P = 0.08). Nighttime symptom score was found to be 0.5
      +/- 0.9 and 0.9 +/- 1.3, respectively (P = 0.07). Usual care group had higher Aas
      score compared to educational group (P = 0.048). The total score of quality of
      life was 197.1 +/- 17.8 in educational group and was 176.7 +/- 33.7 in usual care
      group (P = 0.009). While none of the patients had emergency room application and
      hospital admission in educational group, seven patients had 21 emergency room
      application (P = 0.01) and four patients had four hospital admissions in usual
      care group. Additional short-acting inhaled beta-2 agonist usage was found lower
      in the educational group (P = 0.068). In conclusion, proper drug use and usual
      care of patients are not sufficient for asthma treatment. Patient education is an
      important component of therapy in asthma patients. For a life with optimum
      standards, in addition to these factors, patient education must be accepted first
      by doctors and then by patients.

PMID- 12194638
TI  - Serum eosinophil cationic protein (S-ECP) in a population with low prevalence of
      atopy.
AB  - The study is a part of the European Community Respiratory Health Survey. A random
      sample (n = 351) of 20-44-year olds and persons of the same age with asthma-like
      symptoms or current asthma medication according to a postal questionnaire (n =
      95) were studied. Interview was taken, methacholine challenge was done and ECP,
      total and specific IgE were measured from serum. The median S-ECP value was 8.0
      micrograms/l in the random sample. The geometric mean of S-ECP was higher in
      subjects with, than without atopy (10.2 vs 8.9 micrograms/l, P < 0.01) and in
      subjects with bronchial hyperresponsiveness (BHR) than in subjects without BHR
      (9.9 vs 8.0 micrograms/l, P < 0.01). The levels correlated weakly to forced
      expiratory volume in one second (FEV1) (r = 0.13, P < 0.01) and were not
      independently correlated with respiratory symptoms, asthma or FEV1 after
      adjusting for BHR, IgE, sensitisation and smoking. Our results indicate that the
      level of eosinophil activation is low in a population with a low prevalence of
      atopy, even when BHR is common.

PMID- 12194639
TI  - Activity related increase of exhaled nitric oxide in Crohn's disease and
      ulcerative colitis: a manifestation of systemic involvement?
AB  - Nitric oxide (NO) is an important mediator of inflammation in several
      pathological conditions. Patients with lung diseases, like asthma, have higher
      levels of exhaled NO (eNO) in active disease in comparison with healthy
      volunteers. Aspirated colonic gas in patients with ulcerative colitis (UC) showed
      more than 100 times higher levels of NO in comparison with normal subjects.
      Crohn's disease (CD) and UC are associated with a variety of systemic
      manifestations, although lung diseases as an extra-intestinal expression of
      inflammatory bowel disease (IBD) are not well investigated. In some studies,
      clinical and subclinical pulmonary abnormalities are described in active IBD as
      well as in the stable situation. The aim of the present study is to evaluate
      whether eNO is increased in patients with active IBD and to investigate whether
      there exists a correlation between (1) the eNO levels and the disease activity,
      and (2) the spirometry and the disease activity in a subgroup of patients. In 31
      patients with CD (mean age 36.8 +/- 12.9 years) and 24 patients with UC (mean age
      38.0 +/- 14.7 years) the Crohn's Disease Activity Index (CDAI) and Colitis
      Activity Index (CAI) were measured, respectively. Exhaled NO was measured with a
      chemiluminescence analyzer, according to standardized criteria. In a subgroup of
      CD patients, spirometry was also performed according to standardized criteria.
      The mean CDAI in CD patients was 192.4 +/- 94.3 and their mean eNO value was 13.5
      +/- 4.6 ppb. For UC the mean CAI was 6.2 +/- 4.8 and the mean eNO value was 15.8
      +/- 6.2 ppb. In a matched control group of 27 healthy, non-smoking volunteers
      (mean age of 33.7 +/- 13.2 years) the eNO was 10.2 +/- 2.5 ppb (P < 0.05 compared
      to CD and P < 0.01 compared to UC). There was a disease-activity-related increase
      of the eNO level in patients with IBD. For patients with UC the correlation
      coefficient (r = 0.63, P < 0.001) was more pronounced than for CD (r = 0.39, P <
      0.05). In 17 patients with CD, spirometry was available at the time of the eNO
      measurement. We found a significant negative correlation between the CDAI and the
      FEV1 and FVC in these patients (r = -0.559, P = 0.02 and r = -0.634, P = 0.006,
      respectively). We conclude that eNO is increased in active IBD and correlates
      with the activity of the disease; furthermore, we found a negative correlation
      between spirometry and disease activity in patients with CD. These observations
      strengthen the arguments that IBD is a systemic disease. Further research is
      needed to try to explain the significance of an increased eNO in IBD.

PMID- 12194640
TI  - Adenosine deaminase activity in bronchoalveolar lavage in Turkish patients with
      smear negative pulmonary tuberculosis.
AB  - The sputum smear-negative patients have been a diagnostic challenge for health
      professionals. Adenosine deaminase (ADA) activity has been shown to rise in
      various body fluids of patients with tuberculosis (Tb). A prospective clinical
      trial was conducted to determine the diagnostic value of ADA activity in
      bronchoalveolar lavage (BAL) in sputum smear-negative subjects highly suggestive
      for pulmonary Tb. Nineteen (M/F: 15/4, mean age 46.8 +/- 16.5 years) sputum smear
      negative patients highly suggestive for pulmonary Tb constituted Group I. Acid
      fast bacilli (AFB) grew on sputum and/or BAL culture of all subjects in this
      group. Twenty-nine patients (M/F: 19/10, mean age 55.7 +/- 8.0 years) with non
      tuberculous pulmonary diseases constituted Group II. Ten of them had interstitial
      lung disease, nine lung cancer, five pneumonia and five COPD. Twelve subjects
      (M/F: 7/5, mean age 48.4 +/- 12.8 years) constituted the controls (Group III)
      undergoing fiberoptic bronchoscopy (FOB) for various indications and the lungs
      were found to be normal eventually. Albumin and ADA activity levels were measured
      in plasma and BAL in all the subjects. LocalADA was calculated. PlasmaADA and
      BALADA of Group I was significantly higher (P < 0.001) than that of the other
      groups. LocalADA was also the highest in Group I when compared with the others (P
      < 0.001) but that of Group II was also higher (P < 0.01) when compared with
      controls. With a cut-off value derived from the control subjects, sensitivity of
      BALADA was 100% and specificity 85.3%. Sputum PCR results are available in a
      couple of days whereas that of BALADA are available in a couple of hours and
      BALADA costs cheaper than PCR in our country. Therefore, we conclude that BALADA
      may be a useful, cheaper and faster diagnostic test in sputum smear-negative
      patients highly suggestive for pulmonary Tb. LocalADA need not be calculated as
      it is also significantly higher in Group II subjects and thus not as reliable as
      BALADA.

PMID- 12194641
TI  - Effects of 4-week treatment with low-dose budesonide (100 micrograms BID) from a
      novel inhaler Airmax and from a conventional inhaler on bronchial hyper
      responsiveness, lung function and symptoms in patients with mild asthma.
AB  - This study investigated the effect of low dose of budesonide 100 micrograms b.d
      from a new multi-dose dry powder inhaler (Airmax) and from a conventional inhaler
      (Turbuhaler) on bronchial hyper-responsiveness, lung function and asthma symptoms
      in mild stable asthmatics. Twenty-five patients were enrolled into a double-blind
      double-dummy crossover study with two 4-week treatment periods separated by a 4
      week washout. Patients had a mean forced expiratory volume in 1 s (FEV1) of 91 +/
      13% predicted, had previously received inhaled short-acting beta 2-agonists only
      and had a PC20 to adenosine 5' monophosphate (AMP) < 40 mg/ml. PC20 AMP was
      assessed at baseline, and at the start and end of each treatment period. Patients
      recorded peak expiratory flow and symptoms throughout the study. There was a mean
      increase in PC20AMP from start to end of 3.49 doubling dilutions (DD) in the
      Airmax group and 2.90 DD in the Turbuhaler group. The difference was 0.60 DD (95%
      CI--0.47, 1.69) favouring Airmax and the upper limit exceeded the equivalence
      limit of +/- 1 DD. There were similar improvements in FEV1, daily PEF and
      symptoms in both groups. The majority of patients preferred treatment with Airmax
      to Turbuhaler (64 vs. 23%). Both treatments were equally well tolerated. In
      conclusion, 100 micrograms budesonide bid during 4 weeks from Airmax effectively
      attenuates the response to AMP in mild asthmatics. Overall Airmax offers equal
      clinical benefit to Turbuhaler.

PMID- 12194642
TI  - Pergolide-induced lung disease in patients with Parkinson's disease.

PMID- 12194643
TI  - [Potential role of leptin and insulin resistance assessed by the glucose clamp
      technique in coronary artery disease].
AB  - OBJECTIVES: Leptin may correlate with insulin resistance and be an important
      factor in patients with coronary artery disease. Therefore, we examined whether
      plasma leptin levels and insulin resistance are linked with coronary artery
      disease. METHODS: Plasma leptin levels and insulin resistance, assessed by the
      hyperinsulinemic euglycemic clamp technique, were measured in control subjects (n
      = 12, mean age 62 +/- 10 years), and in patients with obstructive coronary artery
      disease (n = 15, mean age 64 +/- 8 years) or vasospastic angina (n = 12, mean age
      62 +/- 12 years). RESULTS: Plasma leptin levels were significantly higher (p <
      0.017) in patients with obstructive coronary artery disease (8.4 +/- 2.7 ng/ml)
      and vasospastic angina (7.9 +/- 2.1 ng/ml) than in patients without obstructive
      coronary artery disease (4.7 +/- 1.4 ng/ml). Mean glucose infusion rate was
      significantly (p < 0.017) lower in patients with obstructive coronary artery
      disease (4.39 +/- 1.78 mg/kg/min) and vasospastic angina (3.57 +/- 1.72
      mg/kg/min) than in patients without obstructive coronary artery disease (8.74 +/-
      1.05 mg/kg/min). The plasma levels of leptin were negatively correlated with mean
      glucose infusion rate (r = -0.67, p < 0.01). The other coronary risk factors were
      similar in these three groups. CONCLUSIONS: Plasma leptin levels are correlated
      with insulin resistance and may be associated with coronary artery disease.

PMID- 12194644
TI  - [Significance of the antioxidant factor, thioredoxin, in heart failure].
AB  - OBJECTIVES: Increases in oxidative stress may be involved in the progression of
      heart diseases. However, the serum levels of thioredoxin, a redox regulating
      protein, have been poorly investigated in patients with heart diseases. This
      study evaluated the clinical significance of the serum thioredoxin levels in
      patients with heart failure. METHODS: The serum thioredoxin levels were
      determined with a sandwich enzyme-linked immunosorbent assay in a total of 34
      patients with dilated cardiomyopathy (n = 5), acute coronary syndrome (n = 7),
      and stable angina (n = 18), including effort angina (n = 7) and vasospastic
      angina (n = 11), and control subjects (n = 4). RESULTS: The serum thioredoxin
      levels were significantly elevated in patients with acute coronary syndrome (30.6
      +/- 4.9 ng/ml, p < 0.001) and dilated cardiomyopathy (36.9 +/- 8.6 ng/ml, p <
      0.001), but not in patients with stable angina (16.8 +/- 5.7 ng/ml, p = 0.27)
      compared with the control subjects (n = 4, 13.0 +/- 4.9 ng/ml). The serum
      thioredoxin level in patients with III and IV functional classes of the New York
      Heart Association (n = 8, 33.3 +/- 8.6 ng/ml, p < 0.001) was significantly higher
      than in the control subjects. In addition, the serum thioredoxin levels were
      negatively correlated with left ventricular ejection fractions of the patients (r
      = 0.59, p < 0.001). CONCLUSIONS: These results indicate a possible association
      between thioredoxin and the severity of heart failure.

PMID- 12194645
TI  - [Eosinophil infiltration in the heart with free-wall rupture following acute
      myocardial infarction: a case report].
AB  - A 90-year-old woman was referred to us due to acute extensive anterior myocardial
      infarction with cardiogenic shock. Echocardiography revealed akinesis of infarct
      region, associated with wall thinning. She was treated with catecholamines and
      diuretics because her hemodynamics were classified in Forrester subset IV. On the
      ninth day after the onset of infarction, she died of free-wall rupture. The
      postmortem histological study demonstrated eosinophil infiltration in the area of
      rupture, which may have been a pathological factor.

PMID- 12194646
TI  - [Stent implantation for iliac compression syndrome with acute deep vein
      thrombosis: a case report].
AB  - An 80-year-old woman presented with left lower limb pain and swelling with
      tenderness over the great saphenous vein. Venography revealed thrombus in the
      lower leg vein and occlusion of the femoral vein. A temporary vein filter was
      placed below the renal vein and catheter intervention was performed. The wire was
      carefully advanced from the left femoral vein to the vena cava. Hard resistance
      was felt at the proximal iliac vein. After balloon dilation, intravascular
      ultrasonography showed a very flat lumen at the occlusion site. Stent
      implantation was performed followed by anticoagulation therapy. Venography at 3
      months follow-up showed a widely opened iliac vein. Angiography showed the
      occlusion site was the crossing point of the right iliac artery and left iliac
      vein. Stenting for iliac compression syndrome is effective to maintain patency of
      the vein.

PMID- 12194647
TI  - Significant congestive heart failure despite mild mitral stenosis. Anatomically
      mild but functionally severe mitral stenosis.

PMID- 12194648
TI  - Diagnostic, prognostic and therapeutic significances of disappearance of Q waves
      on the electrocardiogram.

PMID- 12194649
TI  - Tipping the scale toward satisfaction is in our control.

PMID- 12194650
TI  - AORN's response to the nursing shortage in perioperative settings.

PMID- 12194651
TI  - Do-not-resuscitate orders in the OR--do they work for the patient?

PMID- 12194652
TI  - The changing face of hand protection.
AB  - Perioperative nurses are empowered to act as patient advocates. As such, it is
      their responsibility to critically evaluate all products used in the surgical
      environment, including gloves. A basic understanding of the history of surgical
      gloves, health issues associated with their use, glove materials, and the
      essential properties of hand scrubs can help perioperative nurses choose
      appropriate products. This article explores these issues so that nurses and other
      health care workers can develop a framework for making informed decisions based
      on clinical reasoning.

PMID- 12194653
TI  - Diabetes mellitus and its chronic complications.
AB  - Diabetes mellitus is a major cause of morbidity and mortality, and it is a major
      risk factor for early onset of coronary heart disease. Complications of diabetes
      are retinopathy, nephropathy, and peripheral neuropathy. Currently, treatment
      involves diet modification, weight reduction, exercise, oral medications, and
      insulin. In recent years, important advances have been made into the pathogenesis
      of diabetes that affect the cardiovascular, renal, and nervous systems; vision;
      and the lower extremities, especially the feet. The progression of diabetic
      retinopathy and nephropathy can be slowed or prevented with tight glucose and
      blood pressure control. Neuropathy remains a major problem causing significant
      impairment. Ongoing clinical trials and testing of various medications to
      determine their effectiveness in treating the complications of diabetes have met
      with some success, but there still is much to learn about this disease.

PMID- 12194654
TI  - Reducing the hazards of exposure to cornstarch glove powder.
AB  - Latex allergy has received considerable attention during the past decade. The
      occurrence of latex allergy in health care workers is higher than in the general
      population. Latex gloves are the most frequent form of exposure that health care
      workers have to natural rubber latex; therefore, the relationship between gloves
      and latex allergies, has been well studied. Scientific evidence supports the link
      between glove powder and the occurrence of latex allergies, as well as the
      development of postoperative complications in surgical patients. This article
      describes how a multihospital system, which is the seventh largest not-for-profit
      health care corporation in the nation and includes 35 ORs, successfully
      eliminated powdered gloves from the environment.

PMID- 12194655
TI  - Do-not-resuscitate orders in the OR--suspend or enforce?
AB  - Retaining self-determination about medical care is a basic patient right. Advance
      directives (e.g., living wills, powers of attorney, health care proxies) are
      becoming more common in today's health care settings, including the OR.
      Perioperative personnel should be aware of and respect these documents and the
      patient's wishes--without compromising their own morals or ethics.

PMID- 12194656
TI  - Performing modified ultrafiltration on pediatric patients.
AB  - Pediatric patients undergoing cardiopulmonary bypass (CPB) surgery often retain
      excessive fluid postoperatively, which results in negative outcomes. Modified
      ultrafiltration (MUF) is an innovative procedure performed at Johns Hopkins
      Hospital, Baltimore, that is initiated immediately after CPB to reduce this
      fluid. This article provides a basic understanding of the MUF technique, how it
      is performed at Johns Hopkins Hospital, and its positive effects.

PMID- 12194657
TI  - Ethics in perioperative practice--duty to self.
AB  - Though often difficult, ethical decision making is necessary when caring for
      surgical patients. Perioperative nurses have to recognize ethical dilemmas and be
      prepared to take action based on the ethical code outlined in the American Nurses
      Association's (ANA's) Code of Ethics for Nurses with Interpretive Statements. In
      this fifth of a nine-part series that will help perioperative nurses relate the
      ANA code to their own area of practice, the author looks at the fifth statement,
      which emphasizes commitment to one's self.

PMID- 12194658
TI  - Benefits of process change in the care and handling of rigid endoscopes.

PMID- 12194659
TI  - Lessons about patient safety from Jean Reeder.

PMID- 12194660
TI  - Advances in orthodontics.

PMID- 12194662
TI  - Cleft lip with or without cleft palate and dermatoglyphic asymmetry: evaluation
      of a Chinese population.
AB  - OBJECTIVE: To determine if Chinese individuals with non syndromic cleft lip with
      or without cleft palate (CL/P) display more dermatoglyphic asymmetry than
      unaffected relatives or controls. DESIGN: Case-control study with two control
      groups (genetically related and unrelated). SETTING AND SAMPLE POPULATION: A
      total of 500 CL/P probands from Shanghai, China, 421 unaffected relatives, and 66
      controls of Chinese heritage. METHODS: Finger and palm prints were collected, and
      pattern frequencies, total ridge counts (TRC), and atd angles were calculated.
      Asymmetry scores between right and left hands were defined for each of the three
      dermatoglyphic measures. Probands' asymmetry scores were compared statistically
      with the scores of unaffected relatives and controls. RESULTS: In general, the
      probands' asymmetry scores for TRC and atd angle did not differ significantly
      from the scores of either unaffected relatives or controls. However, probands
      with a positive family history of clefting showed significantly more asymmetry in
      their pattern types than either probands without a family history, unaffected
      relatives or controls. CONCLUSION: These results suggest that a unique genetic
      mechanism of developmental instability may obtain in CL/P individuals with a
      positive family history of clefting.

PMID- 12194661
TI  - Induced leukemia and antineoplastic agent carmustine cause permanent changes in
      craniofacial growth of immature rats.
AB  - OBJECTIVES: The purpose of the present study was to investigate the possible
      effects of untreated terminal leukemia on craniofacial growth (Study I), and also
      the effects of the antineoplastic agent carmustine on craniofacial growth in both
      leukemic and healthy rats (Study II). MATERIAL: A total of 367 inbred Piebald
      variegated rats was used. METHOD: Transmission of leukemic cells was carried out
      intraperitoneally at 30 days of age, and without treatment (Study I), the rats
      reached the terminal phase within 17 +/- 1 days. Rats with induced leukemia was
      cured with 10 mg/kg carmustine (BCNU) given on days 6 and 13 following cell
      transmission (Study II), the rats remaining in remission until they were killed
      at 100 days of age. Final weight was recorded and 12 craniofacial dimensions and
      tibial length were measured with a digital sliding caliper. RESULTS: The results
      showed that the effect of untreated terminal rat leukemia (Study I) on
      craniofacial growth differed between the genders. Male rats showed clearly
      reduced dimensions of facial structures and also retarded general body growth,
      whereas females showed differences mainly in general body growth. The effect of
      cured leukemia (Study II) as such was minor, while BCNU had a strong and
      permanent reducing effect on both craniofacial and general body growth in both
      genders. CONCLUSION: We suggest that the results in Study I came both from a
      direct effect of leukemia and an indirect effect of untreated terminal leukemia
      through malnutrition. The alkylating agent BCNU seemed to be the main cause of
      permanent craniofacial and general growth retardation in Study II.

PMID- 12194663
TI  - Distribution of fibroblast growth factors (FGFR-1 and -3) and platelet-derived
      growth factor receptors (PDGFR) in the rat mandibular condyle during growth.
AB  - OBJECTIVES: To elucidate the role of the fibroblast growth factors 1 and 3 (FGFR
      1, -3) and the platelet derived growth factor (PDGFR) in the growth of the
      mandibular condylar cartilage in the rat. SETTING AND SAMPLE POPULATION:
      Institute of Dentistry and Department of Biostatistics, University of Turku,
      Turku, Finland. The material consisted of 1- to 21-day-old Long-Evans/Turku rats
      (total of 24 animals, three in each age group). DESIGN: An immunohistological in
      vivo study combined with histomorphometry and biostatistical analysis.
      EXPERIMENTAL VARIABLE: The animals were killed with an overdose of carbon dioxide
      and thereafter decapitated. Heads were fixed in 4% paraformaldehyde, decalcified
      in 12.5% ethylenediaminetetraacetic acid, cut sagittally into two halves and
      sectioned sagittally at 6 microns. In order to detect FGFR-1, -3 and PDGFR the
      sections were treated with H2O2/methanol (1:100), after which FGFR-1 and PDGFR
      monoclonal and FGFR-3 polyclonal antibodies were applied. The reaction products
      were visualized by using the Vectastain ABC Elite Kit using peroxidase substrate
      kit DAB as substrate. Negative and positive controls were also prepared. The
      sections were counterstained with hematoxylin. OUTCOME MEASURE: In order to
      measure the depth of the cell layer labeled with FGF-1, -3 and PDGF receptors,
      the condylar head was divided into four regions: anterior, superior,
      posterosuperior and posterior. The measurements were made perpendicular to the
      articular surface using a computerized image analysis system, the images being
      acquired by means of a microscope connected to a CCD camera. The mean of five
      equally distributed measurements of each region was used to indicate the depth of
      the cell layers secreting the receptors. Regression analysis was used to evaluate
      the association between the depth of the labeled cell layer in relation to total
      depth of the condylar head, as a function of age. RESULTS: Our results show that
      the depth of the cell layer labeled for FGFR-1, -3 and PDGFR increase
      significantly as a function of age in the mandibular condylar head of rats.
      CONCLUSION: Increase in the cell layer labeled for FGFR-1, -3 and PDGFR occurs
      during the stage when the articular function of the mandibular condyle
      intensifies. FGFR-1, -3 and PDGFR evidently have an important role in the growth
      regulation of the condylar cartilage during the most rapid growth period in the
      rat.

PMID- 12194664
TI  - Epidemiological and genetic study of 121 cases of oral clefts in Kuwait.
AB  - AIM: The aim of the study was to ascertain some epidemiological factors such as
      sex and consanguinity that may be associated with cleft lip with or without cleft
      palate (CL +/- CP) in Kuwait as well as to conduct genetic segregation analysis
      of these families. SETTING AND SAMPLE POPULATION: A total of 113 families
      ascertained through 121 CL +/- CP and CP surgical probands in Kuwait. The
      frequencies of cleft types and the epidemiological variables were calculated
      using SPSS version 5.0 software. Chi-square for goodness-of-fit test was used to
      test the significance of the associated epidemiological variables to facial
      clefts. Genetic segregation analysis was performed on 76 families with extended
      pedigrees and included only those with non-syndromic CL +/- CP (NS CL +/- CP).
      Major locus segregation analysis was used to fit models to the observed family
      patterns under Class A regressive models as implemented by REGD routine in
      S.A.G.E. release 4.0. A test for heterogeneity was also conducted to complete
      data set in addition to two subsets: Arabs and nomads. RESULTS: Of the 121
      patients, 34(28.1%) had CP, 30(24.8%) had CL and 57 (47.1%) had CL + CP. The male
      to female ratio was 0.89 for CP, 1.14 for CL, 1.35 for CL + CP and 1.2 for all
      the clefts. The percentage of consanguineous families among those with a positive
      family history (60%) was not significantly different from that of the general
      population (54.3%), whereas for all the families with clefts the percent
      consanguineous was significantly lower (38%). No evidence of heterogeneity in the
      results between the Arab and nomad subsets was observed. The results for the
      major locus segregation analysis were inconclusive. CONCLUSION: No definite
      association was observed between consanguinity and the occurrence of facial
      clefts in Kuwait. General transmission models in the full data set showed no
      evidence of heterogeneity in the results between the Arab and nomad subsets.

PMID- 12194665
TI  - Clinical bond failure of pre-coated and operator-coated orthodontic brackets.
AB  - OBJECTIVES: To test the hypothesis that there is no significant difference in
      clinical bracket failure between the 3M APC Mini Twin bracket system and the
      Transbond XT adhesive during orthodontic treatment. DESIGN: A randomized, split
      mouth, prospective clinical trial. SETTING AND SAMPLE POPULATION: The Department
      of Orthodontics and Dentofacial Orthopedics at University of Missouri, Kansas
      City. Twenty-nine subjects who were treatment planned to receive comprehensive
      orthodontics using 0.018 slot appliances. EXPERIMENTAL VARIABLE: The adhesive pre
      coated brackets (APC) system was randomly assigned to one side of the mouth and
      the Transbond XT was assigned to the opposite side. OUTCOME MEASURE: The absence
      of any of the brackets at the time of a regular or emergency orthodontic
      appointment. RESULTS: There was no significant difference (P > 0.05) in bracket
      failure between the 3M APC Mini Twin bracket system and the Transbond XT adhesive
      at any time period (90, 180, or 365 days). The failure rate of brackets on
      premolars was higher than on incisors or canines. CONCLUSION: APC Mini Twin
      bracket system and Transbond XT adhesive are equally effective in maintaining
      brackets clinically. Inexperienced operators had an overall 7.5% bond failure 12
      months following bracket placement.

PMID- 12194666
TI  - Self-etching vs. traditional bonding systems in orthodontics: an in vitro study.
AB  - The need for a bonding system that is consistently reliable, biocompatible, and
      most of all, easy to use and is unaffected by saliva contamination, has led to
      the development of products that did not require the initial step of etching the
      enamel surface. In these new systems elements of etching, priming and bonding are
      all in one component. The aim of this study was to compare the bonding strength
      of brackets with a traditional technique to the Prompt L-Pop (monocomponent
      adhesive) using the same composite resin. The results showed no statistical
      differences in detachment values of these two groups.

PMID- 12194667
TI  - In vivo evaluation of a moisture-activated orthodontic adhesive: a comparative
      clinical trial.
AB  - OBJECTIVES: To evaluate and compare the clinical performance of a water
      activated, ethyl-cyanoacrylate adhesive to a conventional composite resin. The
      null hypothesis tested was that there was no difference in bracket survival
      distribution, over a period of orthodontic treatment, for brackets bonded with
      either bonding agent. DESIGN: Single center randomized controlled clinical study.
      SETTING AND SAMPLE POPULATION: Twenty-five consecutive patients (15 females and
      10 males) were selected and treated with fixed appliances in a university
      postgraduate orthodontic clinic. All teeth, but the molars, were bonded with twin
      stainless steel brackets (n = 429) using a split-mouth technique and random
      allocation of the two adhesives. OUTCOME MEASURE: Bond failure rates during a
      period of 9 months were estimated for each adhesive system and the corresponding
      bracket survival curves were plotted using the Kaplan-Meier product-limit
      estimate. Bracket survival distributions with respect to adhesive material, tooth
      location, investigator, and bond failure interface were then compared by means of
      a log-rank test. Bond failure interface was determined using the Adhesive Remnant
      Index (ARI). RESULTS: The water-activated bonding material recorded a
      significantly higher bond failure (22.4%) than the composite resin (5.1%). There
      were also statistically significant differences in bracket survival distributions
      between the two adhesives (log-rank test: p < 0.001). Premolars exhibited higher
      bond failure rates than incisors and canines (p < 0001). The predominant mode of
      failure was within the bonding material. CONCLUSION: Further investigations
      focused on the improvement of the physical and mechanical properties of the water
      activated bonding system are needed to make it a reliable alternative adhesive
      for the direct bonding of orthodontic brackets.

PMID- 12194668
TI  - Orthodontic appliances made of organic polymer used in the metal allergic patient
      can withstand orthognathic surgery.
AB  - We developed an orthodontic appliance completely made of organic polymer. The
      appliance was used for many years and proved very effective. It was used for the
      treatment of patients with metal allergy, and as a result, it is believed to be
      the best choice for treating metal allergies. In this report, we are presenting a
      surgical case with Class III malocclusion for a patient with metal allergy, and
      the concept of the appliance is briefly discussed.

PMID- 12194669
TI  - Classification of oral clefts by affection site and laterality: a genotype
      phenotype correlation study.
AB  - OBJECTIVES: The aim of this study was to classify the phenotypes found in a
      series of patients with non-syndromic cleft lip (CL) with or without cleft palate
      (CP) and isolated cleft palate. Additionally, the frequency distribution of cases
      belonging to families linked to markers on chromosomes 6 and 2 within these
      phenotypic patterns were estimated. DESIGN: A retrospective examination of all
      the available affected cases collected in Italy. SETTING AND SAMPLE POPULATION:
      Ninety-seven affected subjects aged 5-18 years belonging to 38 families were
      considered. Patterns were identified by variance of the cleft (lip, primary
      palate, secondary palate) and stratified according to the side of occurrence
      (right, left, or bilateral). Latent class analysis was used as main statistical
      tool for carrying out the results. RESULTS: Three homogenous classes were
      identified (P < 0.0001) by means of latent class analysis. Individuals were
      assigned to the most suited class. All three variables (lip, primary and
      secondary cleft palate) generated a specific class. Optimal findings were
      reported in cases having 'any isolated cleft lip' (class 1); 'secondary CP with
      or without bilateral/right primary cleft palate + bilateral/right cleft lip'
      (class 2); and 'left primary cleft palate + left/bilateral cleft lip with or
      without secondary CP' (class 3). Correspondence to the evidence of linkage to
      chromosome 6 showed that 9 of 10 cases presenting with 'right primary CP + right
      CL with secondary cleft palate' (class 2) belonged to a linked family. The same
      combination, but occurring on the left side (class 3), revealed that only three
      of nine cases belong to families linked to chromosome 6 (P-value = 0.02). The two
      patterns (right and left) never occurred in the same family. Three reliable
      groups were identified based on laterality and the presence of a cleft. A single
      right sided pattern displayed a statistically different distribution of linkage
      to chromosome 6 when compared with the homologous left side. CONCLUSION: Non
      syndromic CL with/without CP can be classified according to laterality that can
      be under genetic control.

PMID- 12194670
TI  - A novel approach for the detection of pathlines in X-ray angiograms: the
      wavefront propagation algorithm.
AB  - This article presents a new pathline approach, based on the wavefront propagation
      principle, and developed in order to reduce the variability in the outcomes of
      the quantitative coronary artery analysis. This novel approach, called wavepath,
      reduces the influence of the user-defined start- and endpoints of the vessel
      segment and is therefore more robust and improves the reproducibility of the
      lesion quantification substantially. The validation study shows that the wavepath
      method is totally constant in the middle part of the pathline, even when using
      the method for constructing a bifurcation or sidebranch pathline. Furthermore,
      the number of corrections needed to guide the wavepath through the correct vessel
      is decreased from an average of 0.44 corrections per pathline to an average of
      0.12 per pathline. Therefore, it can be concluded that the wavepath algorithm
      improves the overall analysis substantially.

PMID- 12194671
TI  - Use of myocardial backscatter as a quantitative tool for dobutamine
      echocardiography: feasibility, response to ischemia and accuracy compared with
      coronary angiography.
AB  - BACKGROUND: Integrated backscatter (IB) changes with ischemia, but most prior
      studies have involved parasternal imaging, which limited the number of evaluable
      segments. We sought to assess the efficacy and feasibility of IB from the apical
      views, and compare this to myocardial Doppler findings and wall motion analysis
      during dobutamine echocardiography. METHODS AND RESULTS: Forty-one patients
      undergoing dobutamine echocardiography had gray scale images and color myocardial
      Doppler acquired in three apical views. Cyclic variation IB (CVIB), time to peak
      IB (tIB, corrected for QT interval) and Doppler peak velocity (PV) in the same
      segment at rest and peak stress were assessed offline from digital cineloops at
      80-120 frames/s. Significant coronary disease was defined by quantitative
      angiography as > 50% stenosis. Analysis of the waveform in the apical views was
      feasible in 82% of segments. The backscatter curve was shown to be biphasic, with
      correlation of the first peak with peak tissue velocity, and significant regional
      variation. However, the response to normal segments was different with tissue
      Doppler (increased velocity) and backscatter (no change). Ischemia was associated
      with a lower peak tissue velocity and lower CVIB. Only resting tissue velocity
      and tIB (not CVIB) distinguished scar from ischemic segments. Using an optimal
      cutoff of < 5.3 dB at rest achieved a sensitivity of 55%, a specificity of 76%
      and an accuracy of 75% when compared to angiography. The same cutoff at peak
      achieved a sensitivity of 58%, a specificity of 80% and an accuracy of 76%.
      CONCLUSIONS: CVIB and tissue velocity responses to stress are different, but both
      may be used to identify abnormal segments in patients with CAD. However, while
      measurement of CVIB is feasible in the apical views, the variability caused by
      anisotropy limits the accuracy of a single cutoff.

PMID- 12194673
TI  - Discordance between dipyridamole technetium-99m-sestamibi myocardial perfusion
      single photon emission computed tomography and two-dimensional echocardiography
      in Kawasaki disease--a preliminary report.
AB  - This study attempts to establish a noninvasive diagnostic method for early
      assessment of cardiac involvement in Kawasaki disease (KD), 36 children with KD
      were studied. The presence of abnormal coronary arteries (CA) with aneurysms was
      determined by experienced pediatric cardiologists using two-dimensional
      echocardiography (2D-Echo). Rest and dipyridamole-stress technetium-99m sestamibi
      (Tc-MIBI) single photon emission computed tomography (SPECT) was performed on the
      36 children with KD for the assessment of myocardial perfusion and for comparison
      with 2D-Echo findings. The results showed that (1) 17/36 (47.2%) of the cases had
      no aneurysm and 19/36 (52.8%) had significant aneurysms; (2) 16/36 (44.4%) of the
      cases had normal myocardial perfusion and 20/36 (55.6%) had myocardial perfusion
      defects; (3) 9/36 (25.0%) cases showed both normal 2D-Echo and Tc-MIBI SPECT
      findings and 12/36 (33.3%) showed both abnormal 2D-Echo and Tc-MIBI SPECT
      findings; and (4) There was poor agreement between 2D-Echo and Tc-MIBI SPECT
      findings (kappa-value = 0.161, p = 0.332). We concluded that the most of the KD
      children had aneurysms or abnormal myocardial perfusion. However, poor agreement
      exists between 2D-Echo and Tc-MIBI SPECT findings with aneurysms and abnormal
      myocardial perfusion in patients with KD.

PMID- 12194674
TI  - Left ventricular cavity-to-myocardium count ratio in exercise and resting
      technetium-99m-tetrofosmin SPECT: correlation with left ventricular function.
AB  - The aim of this study was to assess the value of the cavity-to-myocardium count
      ratio (C/M ratio) calculated in exercise and resting technetium-99m (Tc-99m)
      tetrofosmin single photon emission computed tomography (SPECT) images to identify
      patients with depressed exercise and resting left ventricular ejection fraction
      (LVEF). We studied 60 patients with recent coronary artery diseases (CAD)
      undergoing first-pass ventriculography to calculate LVEF and myocardial perfusion
      SPECT imaging to calculate left ventricular C/M ratios. The group A of 30 CAD
      patients with higher LVEF (> or = 40%) had significant higher C/M ratios than the
      group B of 30 CAD patients with abnormal LVEF (< 40%) during exercise and rest.
      However, C/M ratios between exercise and rest did not differ significantly in the
      both groups A and B. There is significant correlation between exercise/rest LVEF
      and exercise/rest C/M ratios. Tc-99m tetrofosmin C/M ratios calculated SPECT
      perfusion images are useful parameters in identifying patients with depressed
      LVEF in CAD patients.

PMID- 12194672
TI  - Temporal heterogeneity of endothelium-dependent and -independent dilatation of
      brachial artery in patients with coronary artery disease.
AB  - BACKGROUND: Endothelial function is routinely assessed with high frequency
      ultrasound of the brachial artery. Fixed time points (1' post-occlusion and 3'
      post-nitrate) are commonly used to assess dynamic changes in brachial artery
      diameter. The underlying assumption is the lack of variability in temporal
      response to both endothelium-dependent and -independent stimuli. OBJECTIVE: To
      evaluate the temporal course of endothelium-dependent (flow-mediated) and
      endothelium-independent (nitrate-induced) vasodilation of the brachial artery in
      patients with coronary artery disease (CAD) using high resolution (10 MHz)
      ultrasound. METHODS: Thirty-seven patients with angiographically assessed CAD
      were prospectively enrolled in the study. End-diastolic, two-dimensional, long
      axis ultrasonographic images of the brachial artery were digitally stored on-line
      every 10 s, from baseline up to 4' during flow-mediated and up to 7' during 300
      micrograms sublingual nitrate-induced vasodilation of the brachial artery.
      RESULTS: The mean percent endothelium-dependent flow-mediated maximal dilation
      (FMD) measured at 60 s was lower than the mean peak FMD (4.8 +/- 4.1 vs. 6.6 +/-
      5.2%; p < 0.01). By 60 s only eight patients (35%) reached their maximum FMD
      response. The mean time to reach peak FMD was 87 +/- 33 s. The mean time for the
      peak nitrate dilation was 291 +/- 73 s. The peak nitrate-induced percent dilation
      was higher than that measured at 3 min (12.2 +/- 6.7 vs. 5.4 +/- 4.5%; p <
      0.001). By 190 s, only four patients (11%) reached their maximum nitrate
      response. CONCLUSION: The routinely used measurement time points for evaluation
      of FMD and endothelium-independent vasodilation may not be adequate to detect the
      peak responses of individual patients with CAD.

PMID- 12194675
TI  - The cavity-to-myocardial count ratio as a marker of left ventricular function.

PMID- 12194676
TI  - Discordance between dipyridamole stress technetium-99m tetrofosmin single photon
      emission computed tomography and coronary angiography in patients with Kawasaki
      disease.
AB  - Kawasaki disease (KD) is an acute vasculitis syndrome of unknown etiology that
      mainly affects the coronary arteries. The purpose of this study was to assess the
      agreement between dipyridamole stress technetium-99m tetrofosmin (Tc-TF)
      myocardial perfusion single photon emission computed tomography (SPECT) and
      coronary angiography in these patients. Twenty-nine children with KD were
      included in this study. All of the 29 children also received dipyridamole stress
      Tc-TF myocardial perfusion SPECT within 1 month of their coronary angiographic
      studies. The results showed that (1) 89.7% of children had negative coronary
      angiographic findings without significant coronary stenoses, and 10.3% of
      children had positive coronary angiographic findings with significant coronary
      stenosis; (2) 44.8% of children had negative Tc-TF myocardial perfusion SPECT
      findings without abnormal myocardial perfusion, and 55.2% of children had
      positive Tc-TF myocardial perfusion SPECT findings with abnormal myocardial
      perfusion; (3) 44.8% of children had both normal coronary angiographic and Tc-TF
      myocardial perfusion SPECT findings, and 10.3% of children had both abnormal
      coronary angiographic and Tc-TF myocardial perfusion SPECT findings; and (4)
      There was no significant agreement between coronary angiographic and Tc-TF
      myocardial perfusion SPECT findings. We concluded that poor agreement exists
      between coronary angiographic and Tc-TF myocardial perfusion SPECT findings with
      coronary stenoses and abnormal myocardial perfusion in children with KD.

PMID- 12194677
TI  - ECG-gated 18F-FDG positron emission tomography.
AB  - AIM: 18F-fluorodeoxyglucose (18F-FDG)-positron emission tomography (PET) provides
      information about myocardial glucose metabolism to diagnose myocardial viability.
      Additional information about the functional status is necessary. Comparison of
      tomographic metabolic PET with data from other imaging techniques is always
      hampered by some transfer uncertainty and scatter. We wanted to evaluate a new
      Fourier-based ECG-gated PET technique using a high resolution scanner providing
      both metabolic and functional data with respect to feasibility in patients with
      diseased left ventricles. METHODS: Forty-five patients with coronary artery
      disease and at least one left ventricular segment with severe hypokinesis or
      akinesis at biplane cineventriculography were included. A new Fourier-based ECG
      gated metabolic 18F-FDG-PET was performed in these patients. Function at rest and
      18F-FDG uptake were examined in the PET study using a 36-segment model. RESULTS:
      Segmental comparison with ventriculography revealed a high reliability in
      identifying dysfunctional segments (> 96%). 18F-FDG uptake of
      normokinetic/hypokinetic/akinetic segments was 75.4 +/- 7.5, 65.3 +/- 10.5, and
      35.9 +/- 15.2% (p < 0.001). In segments > or = 70% 18F-FDG uptake no akinesia was
      observed. No residual function was found below 40% 18F-FDG uptake. An additional
      dobutamine test was performed and revealed inotropic reserve (viability) in 42
      akinetic segments and 45 hypokinetic segments. CONCLUSION: ECG-gated metabolic
      PET with pixel-based Fourier smoothing provides reliable data on regional
      function. Assessment of metabolism and function makes complete judgement of
      segmental status feasible within a single study without any transfer artefacts or
      test-to-test variability. The results indicate the presence of considerable
      amounts of viable myocardium in regions with an uptake of 40-50% 18F-FDG.

PMID- 12194678
TI  - Magnetic resonance perfusion imaging in patients with coronary artery disease: a
      qualitative approach.
AB  - Although contrast-enhanced first pass magnetic resonance imaging (MRI) has
      potential to quantify blood flow through extensive image post-processing,
      clinical utility is likely to depend on rapid qualitative analysis. AIMS: To
      investigate use of an on-line analytical approach for detection of coronary
      artery disease (CAD). METHODS AND RESULTS: Thirty subjects with CAD underwent
      contrast-enhanced rest/adenosine stress MRI with basal, mid-papillary and apical
      short-axis image acquisition. Each short axis was divided into eight regions of
      interest (ROI). Regional perfusion was visually classified as normal or impaired
      according to transmural distribution and defect reversibility. MRI and
      angiographic data were compared. Qualitative MRI reporting was possible for 98%
      ROI. Eighty-six coronary artery (CA) territories were assessed of which 71 (83%)
      had stenoses. Sensitivity and specificity for detection of stenoses were 93 and
      60%, respectively. The proportion of hypoperfused ROI rose from 31% with < 50%
      stenosis to 65% with occlusion. More transmural defects were seen in infarction
      related territories (75 vs. 54%, p < 0.05). More ROI demonstrated defect
      reversibility in occluded rather than in stenosed infarction-related vessels (89
      vs. 58%, p < 0.05). Occluded vessels with grade 2-3 collaterals contained a
      higher proportion of normal ROI (44 vs. 25%, p < 0.05). CONCLUSIONS: Qualitative
      MRI analysis had high sensitivity and moderate specificity for detecting CA
      stenoses. Additional information was obtained relating to lesion severity,
      previous infarction, myocardial viability and impact of collateral circulation.
      The technique has potential for de novo diagnosis of CAD and as a complementary
      modality to angiography to assess the significance of given angiographic lesions.

PMID- 12194679
TI  - Measurement of left ventricular volume after anterior myocardial infarction:
      comparison of magnetic resonance imaging, echo and radionuclide ventriculography.

PMID- 12194680
TI  - Reproducibility of three different scoring systems for measurement of coronary
      calcium.
AB  - BACKGROUND: There is great interest in measuring and tracking atherosclerosis
      using electron beam tomography (EBT). We sought to assess the reproducibility of
      two new software systems, InSight and AccuImage, and the console workstation of
      an EBT scanner for measuring coronary calcification. METHODS: Two sets of non
      contrast EBT scans were obtained in 85 subjects. The calcium volume (CV) score
      and the Agatston score (AS) were analyzed and the relative differences were
      compared on three workstations. RESULTS: The intra- and inter-observer
      variabilities by InSight and AccuImage were both significantly better than
      variabilities on the console workstation. Both intra- and inter-observer
      differences for the AS were significantly smaller than those for the CV on each
      workstation. However, inter-scan variability was lower for the volume method
      (13.3%) as compared to the AS (17%). Scores were divided into tertiles (T), and
      the relative inter-scan differences for the AS in T-I (scores < 66) were higher
      than those in others (T-I 21.0%, T-II 11.9%, T-III 6.8%, p < 0.01). However,
      there were no significant differences for the CV method (T-I 19.9%, T-II 9.4%,
      and T-III 5.3%). Thus, while intra- and inter-observer differences with the AS
      method was lower than volume scoring, the CV inter-scan variability was
      significantly better. CONCLUSIONS: Both workstations using volumetric and
      Agatston methods have higher reliability than the console workstation. Inter- and
      intra-observer reproducibility was excellent (> 98%). There is minimal inter-scan
      variability for subjects with higher scores (> 65) for both scoring methods.

PMID- 12194681
TI  - [Evaluation of molecular and immunoenzymatic assays for detecting
      Enterohemorrhagic E coli in food borne outbreaks].
AB  - BACKGROUND: Enterohemorrhagic Escherichia coli (EHEC), is an emergent pathogen
      that causes sporadic infections and outbreaks of gastroenteritis associated with
      consumption of contaminated food products. Because detection of EHEC in diarrhea
      patients is not routinely performed, infection is most probably underestimated.
      AIM: To compare three techniques to detect EHEC: Colony hybridization with DNA
      probes, polymerase chain reaction (PCR) for the detection of stx1 and stx2 genes
      and immunoenzymatic detection by ELISA (Premier EHEC) of Stx1 and Stx2 toxins.
      MATERIAL AND METHODS: Four outbreaks of food-borne gastroenteritis were studied
      including 16 patients and 78 strains of E coli. Twenty-one (26.9%) strains,
      hybridized with the stx1 probe, 1 (1.3%) hybridized only with the stx2 probe and
      36 (46.1%) with both probes. PCR amplification for cytotoxin genes was observed
      in 6 strains (7.7%) from the second outbreak studied. The immunoenzymatic assay
      detected the cytotoxins in 18 (23.0%), of the 78 studied strains. Agreement
      between probes and ELISA was 44.8%, between PCR and probes 34.7% and 82.4%
      between ELISA and PCR. CONCLUSIONS: These results indicate a variable yield among
      different EHEC detection techniques. Considering PCR as the gold standard, ELISA
      technique showed a better sensitivity and specificity than probes.

PMID- 12194682
TI  - [Epidemiology of hypertension in chronic hemodialysis].
AB  - BACKGROUND: Hypertension is a common and important cardiovascular risk factor in
      patients on chronic hemodialysis. AIM: To report the prevalence and
      characteristics of hypertension among patients on chronic hemodialysis. PATIENTS
      AND METHODS: Cross sectional study of 313 patients (192 male, aged 57 +/- 18
      years) dialyzed in 7 representative centers in Santiago, Chile. RESULTS: Patients
      were on hemodialysis for a mean of 68 +/- 53 months and 67 (21%) were diabetic.
      230 (74%) were hypertensive and 223 of these (97%) had predialysis hypertension.
      A multivariate analysis showed that hypertension was associated with increased
      weight gain between dialysis, failure to achieve the postdialysis dry weight,
      increasing age and the presence of diabetes. Among hypertensive patients, 61%
      were receiving antihypertensive medications, compared with 27% of patients with
      normal blood pressure. CONCLUSIONS: High blood pressure is highly prevalent among
      patients on chronic hemodialysis and is associated to hypervolemia, age and the
      presence of diabetes.

PMID- 12194683
TI  - [Profile of the treated elderly hypertensive patient].
AB  - BACKGROUND: There is concern about the consequences that hypertension has on the
      well being and mortality of elderly people. AIM: To compare the morbidity and
      mortality of young and old treated hypertensive subjects. MATERIAL AND METHODS:
      Retrospective analysis of hypertensive subjects treated and followed for a period
      of 10 +/- 9 years. Subjects that started treatment at an age of less than 65
      years and those that started treatment after 65 years of age, were analyzed
      separately. The antihypertensive drugs used for treatment and blood pressure
      reduction were similar in both groups. RESULTS: Subjects that started treatment
      after 65 years of age (157 females and 133 males) had lower serum cholesterol
      levels and a higher prevalence of end organ damage than their younger
      counterparts. Women over 65 had a higher body mass index than women of less than
      65. Males over 65 years had a higher prevalence of diabetes than younger males.
      Mortality and complications of hypertension were higher in subjects that started
      treatment after 65 years of age. CONCLUSIONS: The higher mortality of subjects
      that start hypertensive treatment after 65 years of age, is indicative of the
      need to detect and treat hypertension at the earliest possible moment.

PMID- 12194684
TI  - [Detection of BCR-ABL gene sequences using RT-PCR in patients with leukemia in
      the IX region. Chile].
AB  - BACKGROUND: The BCR-ABL fusion gene is the molecular expression of the
      Philadelphia chromosome. This cytogenetic aberration is the most frequent
      alteration found in leukemias, which is produced by the translocation t(9;22).
      Two different fusion proteins are produced depending on the break point (210 kD
      and 190 kD). The detection of this gene has both diagnostic and prognostic
      importance, associated with poor prognosis in acute lymphoblastic leukemia (ALL).
      AIM: To detect BCR-ABL gene sequences in patients with leukemia from the IX
      Region of Chile. MATERIAL AND METHODS: We studied 58 patients: 5 chronic myeloid
      leukemia (CML), 35 ALL, 15 acute myeloid leukemia (AML) and 3 biphenotypic
      leukemia. The gene sequences were detected using reverse transcriptase polymerase
      chain reaction (RT-PCR). RESULTS: BRC-ABL gene sequences were positive in all
      patients with CML, 2 of 35 ALL (one child and one adult). The remaining patients
      were negative. We found p210 and p190 co-expression in 2 CML and 1 ALL.
      CONCLUSIONS: Our results are in agreement with other reports. The detection of
      these and other genetic alterations will allow us to have invaluable diagnostic
      and prognostic information from our patients with leukemia.

PMID- 12194685
TI  - [Williams syndrome: clinical, cytogenetical, neurophysiological and neuroanatomic
      study].
AB  - BACKGROUND: Williams syndrome (WS) is a genetically based disorder caused by
      deletion of elastin and contiguous genes on chromosome 7q11.23. This syndrome is
      characterized by multiorganic involvement with dysmorphic facial features and a
      distinctive cognitive profile. It is an interesting model for elucidation of
      relationships between brain, cognition and genes. Patients have a visual-spatial
      cognition impaired with relative strengths in social and language abilities. AIM:
      To report clinical, cytogenetic, neurophysiological and neuroanatomic features in
      44 patients referred as WS. PATIENTS AND METHODS: Forty four patients, aged 2 to
      17 years, with the clinical diagnosis of Williams syndrome were studied with
      fluorescence in situ hybridization (FISH). In three cases, electrophysiological
      and neuroimaging studies were performed. RESULT: The deletion was confirmed in 23
      patients. In three patients with neurophysiological studies, event related
      potentials suggested a cognitive difficulty in detecting and processing visual
      stimuli. Magnetic resonance imaging showed normal brain morphology. SPECT showed
      hypoperfusion of the right frontal lobe and bilateral anterior cingulum
      hyperperfusion. CONCLUSIONS: There are functional alterations in the brains of
      patients with Williams, which may be related to the cognitive deficits.

PMID- 12194686
TI  - [Unwanted children after birth: frequency measurement and trends analysis].
AB  - BACKGROUND: A significant proportion of pregnancies occurring in Metropolitan
      Santiago are unplanned and unwanted. It is reasonable to postulate that the
      frequency of unwanted children must be high. AIM: To measure the frequency of
      unwanted children in newborns of a public hospital of Santiago. MATERIAL AND
      METHODS: In a period of fourteen months a score assigning survey to detect
      unwanted children was applied, after birth, to 741 women delivering at San Juan
      de Dios Hospital in Metropolitan Santiago. Women whose newborns were hospitalized
      or had congenital malformations were excluded from the survey. RESULTS: Forty
      children (5.4%) scored as unwanted while 52 (7%) qualified as being in a doubtful
      situation. When compared to desired children, unwanted infants had a lower
      frequency of suitable pregnancy controls (p < 0.0002) and a higher incidence of
      mothers declaring bad relations with children's father (p < 0.0002). A trend
      towards higher frequency of single mothers (p: 0.044) was observed. A lower
      frequency of first born children (p: 0.017) and a higher frequency of children
      born in the fourth place, was observed among unwanted newborns (p < 0.002).
      CONCLUSIONS: In the last 15 years, previous studies, carried out with similar
      methodologies, have showed a comparable frequency of unwanted children. These
      condition seems to be associated with poor pregnancy control, high birth order
      and bad relations with the child's father.

PMID- 12194687
TI  - [Vitamin D deficiency in children with chronic diseases evaluated because of
      osteopenia].
AB  - BACKGROUND: Chronic diseases in children may determine limited sun exposure, use
      of drugs, and other risk factors of osteopenia. OBJECTIVE: To evaluate vitamin D
      deficiency and their risk factor, in children with chronic diseases with
      suspected osteopenia. METHODS: We measured bone mineral density, bone remodeling
      markers, calcium, phosphate, parathormone, and 25 hydroxyvitamin D levels, and
      wrist X-ray. RESULTS: We found 8 children of 25 with suspected osteopenia, with
      biochemical abnormalities suggestive of vitamin D deficiency. All children had
      low levels of 25 hydroxyvitamin D, 5 had reduced bone mineral density, 4 had
      hyperparathyroidism, 2 had hyperphosphatasemia, and 1 hypocalcemia and
      hypophosphatemia. None had rickets. DISCUSSION: Osteopenia in chronic sick
      children is due to multiple factors; however, vitamin D deficiency is a
      preventable disorder. We recommend that all children with a chronic disease with
      risk factors for vitamin D deficiency should be monitored with 25 hydroxyvitamin
      D serum levels.

PMID- 12194688
TI  - [Prevalence of psychiatric disorders by alcohol and other substances abuse in men
      and women hospitalized in an internal medicine service of a hospital in Santiago
      de Chile].
AB  - BACKGROUND: Studies done in Chile and abroad report a high frequency of substance
      abuse among patients hospitalized in general medical services. AIM: To report the
      frequency of substance abuse in a sample of patients hospitalized in a public
      hospital of Santiago. MATERIAL AND METHODS: A structured psychiatric interview
      for the Third Revised Version of The Diagnostic and Statistical Manual (DSM-III
      R) was applied to 203 males, aged 58.5 years and 203 females, aged 52.9 years,
      hospitalized in an internal medicine Service of a public hospital. All subjects
      had a low educational and income level. RESULTS: The discharge diagnoses of
      studied patients were digestive diseases in 32%, circulatory diseases in 19%,
      cancer, diabetes mellitus and genitourinary diseases in 11% respectively and
      mental or behavioral diseases in 5%. Thirty eight percent of males and 6% of
      females qualified for alcohol dependency or abuse in some moment of their lives.
      The figures for benzodiazepine dependency were 1% among males and 6% among
      females. The figures for cannabis, cocaine or stimulant abuse were 1.5% for males
      and 1% for females. Other conditions of the axis 1 of DSM-IIIR were diagnosed in
      47% of males and 65% of females with substance abuse. CONCLUSIONS: Substance
      abuse underlies medical conditions in a high proportion of patients admitted to
      medical services in general hospitals.

PMID- 12194690
TI  - [Ischemic colitis induced by cocaine. Clinical case].
AB  - We report a 29 years old male, with a history of cocaine abuse and excessive
      alcohol intake, who was admitted to the hospital with an acute peritonitis. The
      patient was operated and multiple perforations of the cecum were found. A right
      hemicolectomy was performed and the pathological study of the surgical piece
      showed an ischemic colitis. A literature review reveals 22 reported cases of
      ischemic colitis associated to cocaine abuse.

PMID- 12194689
TI  - [Systemic yeast infections in a general hospital. Correlation between study of
      susceptibility in vitro and patient survival to the fungal infection episode].
AB  - BACKGROUND: Fungi are important causal agents of nosocomial infections, that
      usually have high mortality rates. AIM: To evaluate the species distribution and
      susceptibility patterns of deep yeast infections in a General Hospital and to
      correlate those results with patient survival. MATERIAL AND METHODS: Twenty one
      strains (from five pediatric and 16 from adult patients) were studied. Antifungal
      Susceptibility Testing (AST) to Amphotericin B (Anfb), Fluorocytosine (5FC),
      Fluconazole (FZ) and Itraconazole (IZ) was performed according to the EUCAST
      document. Clinical data of patients was obtained and survival to the infection
      was recorded. RESULTS: C. albicans was isolated in 11 samples (52%), C.
      parapsilosis in three samples (14%), C. glabrata in two samples (9%), C.
      tropicalis in one sample (5%) and C. neoformans in four samples (19%). Twenty
      three percent of fungi were recovered at the Surgical Intensive Care Unit. The
      MICs ranged between 0.25 and 0.5 microgram/mL for Anfb; between 0.25 and 16
      micrograms/ml for SFC, between 0.12 and 32 micrograms/mL for FZ and 0.015 and 0.5
      microgram/mL for IZ. No association between antifungal susceptibility and patient
      survival was observed. CONCLUSIONS: C. albicans continues to be the most
      frequently isolated yeast, however, non-albicans species are an emergent group
      causing nosocomial infections. Surgical procedures are the main source of fungal
      infections in this sample.

PMID- 12194691
TI  - [Glucagonoma: evolution and treatment].
AB  - Glucagonomas are alpha pancreatic islet cell tumors that, when they are active,
      produce a syndrome characterized by necrolytic migratory erythema, diabetes
      mellitus, weight loss, anemia, glossitis, thromboembolism, neuropsychiatric
      disturbances and hyperglucagonemia. We report a 43 years old male presenting with
      a five years history of dermatological lesions, associated with weight loss,
      glossitis and onicodystrophy. Serum glucagon was 2200 pg/ml and a CAT scan showed
      a tumor in the tail of the pancreas. The tumor was surgically excised but one
      year later, hepatic metastases were found. These were excised surgically, treated
      with long acting octeotride and finally treated with radiotherapy using Y
      DOTATOC. In the last control in November, 2001, the patient is asymptomatic.

PMID- 12194692
TI  - [Hemolytic-uremic syndrome and Streptococcus pneumoniae].
AB  - Hemolytic-uremic syndrome (HUS) is an uncommon complication of pneumococcal
      infection. Highly suggesting findings in a patient with Streptococcus pneumoniae
      infection are: microangyopatic hemolytic anemia, thrombocytopenia and acute renal
      failure. We report a 41 years old woman, admitted to the hospital due to a severe
      pneumonia, that required the surgical drainage of an empyema. On admission, a
      drop in packed red cell volume from 41 to 25%, the presence of schistocytes in
      the blood smear, an elevation of LDH to 1,700 IU/L, a fall in haptoglobin to 5.8
      mg/dL and a thrombocytopenia of 72,000 per mm3 were detected. These alterations
      coincided with an oliguric acute renal failure. She was treated with hemodialysis
      and the hemolytic syndrome was managed with plasmapheresis. She was discharged 35
      days after admission and in the follow up, after 2.5 months, her serum creatinine
      is 1.2 mg/dL and her packed red cell volume is 41%.

PMID- 12194693
TI  - Alcohol-induced liver disease: from molecular damage to treatment.
AB  - Although the interaction between alcohol and the liver has been the subject of
      intensive investigation since many years, several uncertainties remain to be
      solved. Good examples of what we need to learn are: The real number of patients
      with alcohol-induced liver disease (AILD), the dose of alcohol "safe" for the
      liver, the genetic predisposition to the damage or, on the other side of the
      coin, protecting from the damage. Rather recently, however, part of these
      questions started to be clarified, thus permitting a better definition of the
      role of each of these factors in AILD. In parallel to the clinical approach to
      AILD, the unveiling of the molecular and biochemical mechanisms involved in AILD
      has progressed and proved to be important in both a better understanding of the
      disease and, more important, in a more rational treatment of these disorders.
      This review will focus on what we currently know of AILD in clinical, biochemical
      and molecular terms and what we need to address in the future.

PMID- 12194694
TI  - [Fulminant hepatic failure].
AB  - Fulminant hepatic failure (FHF) is an acute and eventually fatal illness, caused
      by a severe hepatocyte damage with massive necrosis. Its hallmarks are hepatic
      encephalopathy and a prolonged prothrombin time (< 40%). FHF is currently defined
      as hyperacute (encephalopathy appearing within 7 days of the onset of jaundice),
      acute (encephalopathy appearing between 8 and 28 days) or subacute
      (encephalopathy appearing between 5 and 12 weeks). FHF can be caused by viruses,
      drugs, toxins, and miscellaneous conditions such as Wilson's disease, Budd-Chiari
      syndrome, ischemia and others. However, a single most common etiology is still
      not defined. Factors that are valuable in assessing the likelihood of spontaneous
      recovery are age, etiology, degree of encephalopathy, prothrombin time and serum
      bilirubin. The management is based in the early treatment of infections,
      hemodynamic abnormalities, cerebral edema, and other associated conditions. Liver
      transplant has emerged as the most important advance in the therapy of FHF, with
      a survival rate that ranges between 60 and 80%. The use of hepatic support
      systems, extracorporeal liver support and auxiliary liver transplantation are
      innovative therapies.

PMID- 12194695
TI  - [Technological advances: the coming radiology].
AB  - We are living in a changing world, acknowledging all kinds of changes: social,
      technological, and ethical. This is the environment encircling medical and
      radiological work: demanding, with high expectations and a cohort of amazing
      technological advances, in all areas of human knowledge. We need to make the
      necessary reflections about these faster and faster changes. Radiology, as an
      important part of clinical work, is facing no minor challenges: technological and
      other most prevalent like: Who will be specialists in the next future? How are we
      prepared to face the radiological teaching and formation of radiologists? How to
      finance this technological developments? Meanwhile, in our context of an
      underdeveloped country, this sounds as far as the Moon, but changes will reach us
      sooner or later. We must resolve some problems that are a little bit more basic,
      such as a good level of education and health care for our people, then we will be
      ready to incorporate some of these amazing new technologies.

PMID- 12194696
TI  - [Clinical importance of hypercholesterolemia].

PMID- 12194697
TI  - [Clinical importance of hypercholesterolemia].

PMID- 12194698
TI  - [Acute confusional syndrome associated to Chlormezanone use].

PMID- 12194699
TI  - Appetite suppressants and valvular heart disease - a systematic review.
AB  - BACKGROUND: Although appetite suppressants have been implicated in the
      development of valvular heart disease, the exact level of risk is still
      uncertain. Initial studies suggested that as many as 1 in 3 exposed patients were
      affected, but subsequent research has yielded substantially different figures.
      Our objective was to systematically assess the risk of valvular heart disease
      with appetite suppressants. METHODS: We accepted studies involving obese patients
      treated with any of the following appetite suppressants: fenfluramine,
      dexfenfluramine, and phentermine. Three types of studies were reviewed:
      controlled and uncontrolled observational studies, and randomized controlled
      trials. Outcomes of interest were echocardiographically detectable aortic
      regurgitation of mild or greater severity, or mitral regurgitation of moderate or
      greater severity. RESULTS: Of the 1279 patients evaluated in seven uncontrolled
      cohort studies, 236 (18%) and 60 (5%) were found to have aortic and mitral
      regurgitation, respectively. Pooled data from six controlled cohort studies
      yielded, for aortic regurgitation, a relative risk ratio of 2.32 (95% confidence
      intervals 1.79 to 3.01, p < 0.00001) and an attributable rate of 4.9%, and for
      mitral regurgitation, a relative risk ratio of 1.55 (95% confidence intervals
      1.06 to 2.25, p = 0.02) with an attributable rate of 1.0%. Only one case of
      valvular heart disease was detected in 57 randomized controlled trials, but this
      was judged unrelated to drug therapy. CONCLUSIONS: The risk of valvular heart
      disease is significantly increased by the appetite suppressants reviewed here.
      Nevertheless, when considering all the evidence, valvulopathy is much less common
      than suggested by the initial, less methodologically rigorous studies.

PMID- 12194700
TI  - Polycystic kidney disease in patients on the renal transplant waiting list:
      trends in hematocrit and survival.
AB  - BACKGROUND: The patient characteristics and mortality associated with autosomal
      dominant polycystic kidney disease (PKD) have not been characterized for a
      national sample of end stage renal disease (ESRD) patients on the renal
      transplant waiting list. METHODS: 40,493 patients in the United States Renal Data
      System who were initiated on ESRD therapy between 1 April 1995 and 29 June 1999
      and later enrolled on the renal transplant waiting list were analyzed in an
      historical cohort study of the relationship between hematocrit at the time of
      presentation to ESRD and survival (using Cox Regression) in patients with PKD as
      a cause of ESRD. RESULTS: Hematocrit levels at presentation to ESRD increased
      significantly over more recent years of the study. Hematocrit rose in parallel in
      patients with and without PKD, but patients with PKD had consistently higher
      hemoglobin. PKD was independently associated with higher hematocrit in multiple
      linear regression analysis (p < 0.0001). In logistic regression, higher
      hematocrit was independently associated with PKD. In Cox Regression analysis, PKD
      was associated with statistically significant improved survival both in
      comparison with diabetic (hazard ratio, 0.64, 95% CI 0.53-0.77, p < 0.001) and
      non-diabetic (HR 0.68, 95% CI 0.56-0.82, p = 0.001) ESRD patients, adjusted for
      all other factors. CONCLUSIONS: Hematocrit at presentation to ESRD was
      significantly higher in patients with PKD compared with patients with other
      causes of ESRD. The survival advantage of PKD in ESRD persisted even adjusted for
      differences in hematocrit and in comparison with patients on the renal transplant
      waiting list.

PMID- 12194701
TI  - Identifying older diabetic patients at risk of poor glycemic control.
AB  - BACKGROUND: Optimal glycemic control prevents the onset of diabetes
      complications. Identifying diabetic patients at risk of poor glycemic control
      could help promoting dedicated interventions. The purpose of this study was to
      identify predictors of poor short-term and long-term glycemic control in older
      diabetic in-patients. METHODS: A total of 1354 older diabetic in-patients
      consecutively enrolled in a multicenter study formed the training population
      (retrospective arm); 264 patients consecutively admitted to a ward of general
      medicine formed the testing population (prospective arm). Glycated hemoglobin
      (HbA1c) was measured on admission and one year after the discharge in the testing
      population. Independent correlates of a discharge glycemia > or = 140 mg/dl in
      the training population were assessed by logistic regression analysis and a
      clinical prediction rule was developed. The ability of the prediction rule and
      that of admission HbA1c to predict discharge glycemia > or = 140 mg/dl and HbA1c
      > 7% one year after discharge was assessed in the testing population. RESULTS:
      Selected admission variables (diastolic arterial pressure < 80 mmHg, glycemia =
      143-218 mg/dl, glycemia > 218 mg/dl, history of insulinic or combined
      hypoglycemic therapy, Charlson's index > 2) were combined to obtain a score
      predicting a discharge fasting glycemia > or = 140 mg/dl in the training
      population. A modified score was obtained by adding 1 if admission HbA1c exceeded
      7.8%. The modified score was the best predictor of both discharge glycemia > or =
      140 mg/dl (sensitivity = 79%, specificity = 63%) and 1 year HbA1c > 7%
      (sensitivity = 72%, specificity = 71%) in the testing population. CONCLUSION: A
      simple clinical prediction rule might help identify older diabetic in-patients at
      risk of both short and long term poor glycemic control.

PMID- 12194702
TI  - Phylogenetic relationships and taxonomic position of Chlorella-like isolates from
      low pH environments (pH < 3.0).
AB  - BACKGROUND: Little is known about phytoplankton communities inhabiting low pH
      environments such as volcanic and geothermal sites or acidic waters. Only
      specialised organisms are able to tolerate such extreme conditions. There is,
      thus, low species diversity. We have characterised the previously isolated acid
      tolerant Chlorella-like microalgae Viridiella fridericiana and Chlorella
      protothecoides var. acidicola by microscopical and biomolecular methods in order
      to assess their phylogenetic relationships. RESULTS: Both isolates belong to the
      trebouxiophycean lineage of chlorophytes. 18S and ITS1 sequence data clearly
      confirm that Viridiella fridericiana constitutes a new genus apart from the
      morphologically similar and likewise acid tolerant microalga Chlorella
      saccharophila. Chlorella protothecoides var. acidicola on the other hand is not a
      variety of Chlorella protothecoides but falls within a heterogeneous cluster
      consisting of Nannochloris, "Chlorella" spec. Yanaqocha, and Koliella, and is
      most closely related to algae which were also isolated from extreme environments.
      CONCLUSIONS: The distribution of acid tolerant strains in the 18S rRNA tree shows
      that acquisition of acid tolerance was unlikely a monophyletic event in green
      microalgae. We propose that different strains have independently adapted to
      extreme environments. Some of them have spread worldwide and were able to
      colonise other extreme habitats. Considering the problems of successfully
      isolating acid tolerant strains, acidic soils could represent an unsuspected
      source of biological diversity with high potential for biotechnological
      utilisations.

PMID- 12194703
TI  - Microarray results: how accurate are they?
AB  - BACKGROUND: DNA microarray technology is a powerful technique that was recently
      developed in order to analyze thousands of genes in a short time. Presently,
      microarrays, or chips, of the cDNA type and oligonucleotide type are available
      from several sources. The number of publications in this area is increasing
      exponentially. RESULTS: In this study, microarray data obtained from two
      different commercially available systems were critically evaluated. Our analysis
      revealed several inconsistencies in the data obtained from the two different
      microarrays. Problems encountered included inconsistent sequence fidelity of the
      spotted microarrays, variability of differential expression, low specificity of
      cDNA microarray probes, discrepancy in fold-change calculation and lack of probe
      specificity for different isoforms of a gene. CONCLUSIONS: In view of these
      pitfalls, data from microarray analysis need to be interpreted cautiously.

PMID- 12194704
TI  - Stroke: a review with an African perspective.
AB  - The frequency of stroke and stroke-associated mortality are higher in Blacks than
      in other races. Several of the known risk factors for stroke, such as
      hypertension, diabetes and obesity, are more common in Blacks than Whites, and
      sickle-cell disease and HIV infection are stroke risk factors with particular
      relevance to Africans. Although the facilities for accurate stroke diagnosis and
      classification are unavailable in most parts of Africa, careful analysis of the
      clinical features can minimize the rates of misdiagnosis and misclassification.
      The high levels of stroke-attributable morbidity and mortality observed in
      Africans could be markedly reduced by instituting primary and secondary
      preventive measures and by educating health-care professionals on stroke
      management strategies.

PMID- 12194705
TI  - The drug sensitivity and transmission dynamics of human malaria on Nias Island,
      North Sumatra, Indonesia.
AB  - Nias Island, off the north-western coast of Sumatra, Indonesia, was one of the
      first locations in which chloroquine-resistant Plasmodium vivax malaria was
      reported. This resistance is of particular concern because its ancient megalithic
      culture and the outstanding surfing conditions make the island a popular tourist
      destination. International travel to and from the island could rapidly spread
      chloroquine-resistant strains of P. vivax across the planet. The threat posed by
      such strains, locally and internationally, has led to the routine and periodic re
      assessment of the efficacy of antimalarial drugs and transmission potential on
      the island. Active case detection identified malaria in 124 (17%) of 710 local
      residents whereas passive case detection, at the central health clinic, confirmed
      malaria in 77 (44%) of 173 cases of presumed 'clinical malaria'. Informed
      consenting volunteers who had malarial parasitaemias were treated, according to
      the Indonesian Ministry of Health's recommendations, with sulfadoxine
      pyrimethamine (SP) on day 0 (for P. falciparum) or with chloroquine (CQ) on days
      0, 1 and 2 (for P. vivax). Each volunteer was then monitored for clinical and
      parasite response until day 28. Recurrent parasitaemia by day 28 treatment was
      seen in 29 (83%) of the 35 P. falciparum cases given SP (14, 11 and four cases
      showing RI, RII and RIII resistance, respectively). Recurrent parasitaemia was
      also observed, between day 11 and day 21, in six (21%) of the 28 P. vivax cases
      given CQ. Although the results of quantitative analysis confirmed only low
      prevalences of CQ-resistant P. vivax malaria, the prevalence of SP resistance
      among the P. falciparum cases was among the highest seen in Indonesia. When the
      parasites present in the volunteers with P. falciparum infections were genotyped,
      mutations associated with pyrimethamine resistance were found at high frequency
      in the dhfr gene but there was no evidence of selection for sulfadoxine
      resistance in the dhps gene. Night-biting mosquitoes were surveyed by human
      landing collections and tested for sporozoite infection. Among the five species
      of human-biting anophelines collected, Anopheles sundaicus was dominant (68%) and
      the only species found to be infective--two (1.2%) of 167 females being found
      carrying P. vivax sporozoites. The risk of malarial infection for humans on Nias
      was considered high because of the abundance of asymptomatic carriers, the
      reduced effectiveness of the available antimalarial drugs, and the biting and
      infection 'rates' of the local An. sundaicus.

PMID- 12194706
TI  - The humoral immune responses elicited in mice by inoculations with a recombinant
      protein or DNA based on the circumsporozoite-protein gene of Plasmodium
      falciparum.
AB  - The humoral responses elicited in mice by inoculation, in various doses and by
      several routes, with plasmid DNA containing the gene coding for the
      circumsporozoite protein (CSP) of Plasmodium falciparum FCC1/HN were compared
      with those evoked by inoculation with a recombinant expressed protein based on
      the CSP. With the DNA vaccine, intramuscular inoculations appeared the most
      effective, followed by intravenous and then subcutaneous injections, the
      responses in each case being dose-dependent. In both standard ELISA and dot
      ELISA, sera from the mice immunized with the DNA were found to have much lower
      titres of antimalarial antibodies than the corresponding sera from mice immunized
      with the recombinant protein. Although both 'vaccines' elicited humoral immune
      responses in BALB/c mice, that based on plasmid DNA took much longer than the
      recombinant protein to induce high-titre antibody responses.

PMID- 12194707
TI  - The identification, cloning and functional expression of the gene encoding
      orotidine 5'-monophosphate (OMP) decarboxylase from Plasmodium falciparum.
AB  - The coding region of a putative orotidine 5'-monophosphate decarboxylase gene
      from Plasmodium falciparum was identified in genomic data from the Malarial
      Genome Sequencing Project. The gene encodes a protein of 323 amino acids with a
      predicted molecular weight of 37.8 kDa. The gene was cloned into a bacterial
      expression vector and over-expressed in Escherichia coli. The recombinant protein
      was purified and shown to have orotidine 5'-monophosphate decarboxylase activity,
      confirming the identity of the gene.

PMID- 12194708
TI  - Anaemia during pregnancy in southern Tanzania.
AB  - Anaemia in pregnancy is associated with maternal morbidity and mortality and is a
      risk factor for low birth-weight. Of 507 pregnant women recruited in a community,
      cross-sectional study in southern Tanzania, 11% were severely anaemic (<8 g
      haemoglobin/dl). High malarial parasitaemia [odds ratio (OR)=2.3] and iron
      deficiency (OR=2.4) were independent determinants of anaemia. Never having been
      married (OR=2.9) was the most important socio-economic predictor of severe
      anaemia. A subject recruited in the late dry season was six times more likely to
      be severely anaemic than a subject recruited in the early dry season. Compared
      with the women who were not identified as severely anaemic, the women with severe
      anaemia were more likely to present at mother-and-child-health (MCH) clinics
      early in the pregnancy, to seek medical attention beyond the MCH clinics, and to
      report concerns about their own health. Pregnancy-related food taboos in the
      study area principally restrict the consumption of fish and meat. Effective anti
      malaria and iron-supplementation interventions are available but are not
      currently in place; improvements in the mechanisms for the delivery of such
      interventions are urgently required. Additionally, opportunities for contacting
      the target groups beyond the clinic environment need to be developed.

PMID- 12194709
TI  - Schistosome transmission, water-resource development and altitude in northern
      Ethiopia.
AB  - Schistosomiasis continues to be a major public-health problem, not least in
      association with water-resource developments. The impact of microdam construction
      in the northern Ethiopian highlands, in relation to possible increased risks of
      Schistosoma mansoni infection, has now been assessed. The results of incidence
      studies, carried out on 473 individuals sampled across eight microdam sites at
      altitudes of 1800-2225 m above sea level, indicated an overall annual incidence
      of 0.20 infections/person at risk. A multivariate Poisson regression model showed
      altitude and sex to be significant risk factors for infection, whereas proximity
      to a microdam was not significant, except possibly at very high altitudes. It was
      concluded that altitude was the major factor in this environment and that
      therefore, at least in terms of public-health planning, microdams should be sited
      as high as local geography permits.

PMID- 12194710
TI  - Subconjunctival zoonotic onchocerciasis in man: aberrant infection with
      Onchocerca lupi?
AB  - In the past few decades, 10 cases of cryptic, zoonotic onchocerciasis, including
      two subconjunctival infections, have been reported in man. In the majority of
      cases, Onchocerca cervicalis, O. gutturosa or O. dewittei, which normally infect
      horses, cattle and wild boar, respectively, were responsible for the lesions.
      However, the taxonomic status of the parasites involved in the two
      subconjunctival infections, both of which were European, has never been
      unambiguously determined. In such infections, the acute phase appears to be
      characterized by conjunctivitis. A single, strongly coiled, immature, female worm
      was found incorporated in a large granulomatous nodule, in the ocular and peri
      ocular tissues, in the chronic stage of each of the two eye infections. Several,
      patent, sporadic cases of subconjunctival O. lupi infection have recently been
      reported in dogs. In terms of the location of the worms, clinical signs and
      histopathology, these canine infections were very similar to those seen in the
      two human patients with eye infection. When the parasites recovered from human
      eyes were compared morphologically with the Onchocerca spp. infecting animals in
      Europe, they appeared to be most similar to O. lupi. Although O. lupi is normally
      a parasite of dogs, it may thus also be responsible for aberrant, zoonotic,
      subconjunctival infections in man.

PMID- 12194711
TI  - Intestinal parasitic infections in young children in Sao Paulo, Brazil:
      prevalences, temporal trends and associations with physical growth.
AB  - The prevalences of intestinal parasitic infections were investigated, between
      1995 and 1996, in a household-based sample of 1044 children aged <5 years who
      lived in the city of Sao Paulo, Brazil. Only 10.7% of the children were infected,
      the most prevalent parasites being Giardia duodenalis (5.5%), Ascaris
      lumbricoides (4.4%) and Trichuris trichiura (1.0%). A comparison between these
      data and results from two previous population-based surveys, completed in Sao
      Paulo in 1974 and 1985, revealed a dramatic decrease in the prevalence of
      intestinal helminths in this age-group, with less marked changes in the
      prevalence of Giardia, over the two past decades. Despite the low prevalence of
      malnutrition (2.4% of stunting and 0.6% of wasting) and intestinal parasites in
      this population, there was a significant association (P=0.05, after controlling
      for potential confounding variables) between helminth (but not Giardia) infection
      and height. The helminth-infected children had a mean height-for-age z-score of
      0.412 [95% confidence interval (CI)=-0.637--0.186], compared with one of 0.015
      (CI=-0.049-0.079) for the non-infected children. No significant relationship
      between intestinal parasitic infection and children's weight was detected. In
      conclusion, a small but significant negative relationship between intestinal
      helminthic infections and children's growth was detected in an urban environment
      with low prevalences of both intestinal parasitic infection and malnutrition.

PMID- 12194712
TI  - Causative agents of liver abscess in those with liver cirrhosis: a 10-year case
      review of hospitalized patients in Thailand.
AB  - Although patients with cirrhosis of the liver show relative immunosuppression and
      therefore have increased susceptibility to most infections, they rarely develop
      liver abscesses. In a retrospective case review, the pathogens causing the liver
      abscesses observed, between January 1992 and December 2001 at the King
      Chulalongkorn Memorial Hospital, Bangkok, Thailand, in 44 hospitalized patients
      diagnosed as cases of liver cirrhosis were investigated. The most common clinical
      symptoms and signs of the abscesses--abdominal pain (80%), fever and chills
      (73%), and abdominal tenderness (73%)--were similar to those seen in non
      cirrhotic patients with abscesses. The frequency of liver abscess among the
      cirrhotic patients was low (0.46%). Most (71%) of the abscesses were in the right
      lobe and most (71%) of those with abscesses only had a single abscess.
      Surprisingly, many of the abscesses (36%) were apparently caused by amoebae.
      Bacterial pathogens were identified in eight patients (18%) by blood culture and
      15 (34%) patients by pus culture. Seven (16%) of the blood cultures and 13 (30%)
      of the pus contained Gram-negative aerobes, indicating that such pathogens,
      particularly Klebsiella pneumoniae (in six pus and six blood cultures) and
      Escherichia coli (in three pus cultures and one blood), were the most common
      causes of the bacterial abscesses. Pus culture appeared more successful than
      blood culture for bacterial abscesses, and amoebic abscesses could always be
      identified by direct microscopical examination of pus samples. Aspiration of
      liver abscesses, to obtain pus samples for culture and microscopy, is therefore
      recommended.

PMID- 12194713
TI  - Needle-stick injuries in an Ugandan teaching hospital.
AB  - The on-going HIV epidemic has generally increased fear of needle-stick injuries
      (NSI) and renewed interest in the problem such injuries pose in Africa. The aims
      of the present study were to evaluate the frequency of NSI, explore the
      circumstances surrounding each injury and estimate the corresponding infection
      risk, among healthcare workers (HCW) in Uganda. Questionnaires, asking the
      recipients how many NSI they had suffered in the past year, how each of these NSI
      had occurred, what (perceived) risk of infection was associated with each injury,
      and what their practical and psychological reactions were, were sent to the HCW
      associated with the Mbarara Teaching Hospital in Uganda. Of the 280 individuals
      who received questionnaires, 180 (64%) responded and 100 (55% of the respondents)
      each reported suffering at least one NSI in the previous year. The total number
      of NSI reported (336) represented an incidence of 1.86 NSI/HCW-year. Interns
      suffered more NSI (annual mean=4.8) than any other occupational group. Most NSI
      occurred when patients moved during procedures, when HCW re-sheathed needles, or
      during suturing (each reported by 55 HCW--30% of those responding). Following
      NSI, 60 HCW said they squeezed the site of the injury and washed it with bleach,
      43 believed they had a 10% risk of HIV infection, 87 felt anxious, 54 felt
      depressed, 40 prayed, 24 had an HIV test, and four were counselled. To estimate
      actual infection risk, 435 patients were screened for antibody to HIV (1 and 2)
      and for the surface antigen of the hepatitis B virus (HBSAg); 26% and 2.8% were
      found seropositive, respectively. These seroprevalences were multiplied by
      previously determined probabilities of transmission to give estimated risks of
      infection (following a single NSI) of 0.08% for HIV and 0.135% for hepatitis B.
      During 3 years of training as a clinician (i.e. 2 years as a medical student and
      1 year as an intern), more than six in 1000 individuals would be infected with
      HIV as a result of NSI and almost 10 in 1000 would be infected with hepatitis B
      virus by the same route. NSI are common, preventable sources of infection and
      stress for HCW in Africa.

PMID- 12194714
TI  - The demonstration, staining and prevalences, in pathological and non-pathological
      specimens, of eosinophils in faeces.
AB  - Although eosinophils are occasionally reported in mucus there has been no
      description of them in faecal samples. Attempts were made to demonstrate
      eosinophils in stool samples using several different staining techniques. Use of
      an acid dye, Acid Red 29, was found to be the simplest and most direct method of
      revealing eosinophils, producing very characteristic, orange-brown, sometimes
      red, staining of the intracellular granules that contain eosinophil cationic
      protein. In stool samples held at room temperature, without preservative,
      eosinophils remained demonstrable for a mean of 15 days and occasionally for a
      year. The peroxidase in the eosinophilic granules may help to preserve the cells.
      Eosinophils were found in 32 (14%) of 223 stool samples from patients with
      intestinal disease (including the results of several parasitic infections) but in
      none of 72 samples from apparently healthy hospital personnel (P<0.001).
      Eosinophils were never found in formed stool specimens that did not contain
      mucus. The demonstration of eosinophils in faecal samples may be a useful
      indicator of infection with intestinal helminths or of drug- or food-related
      digestive allergies.

PMID- 12194715
TI  - Allogeneic marrow transplantation--dinosaur or bird?

PMID- 12194717
TI  - Autologous hematopoietic transplantation for low-grade lymphomas.
AB  - BACKGROUND: Autologous stem cell transplantation (SCT) has become the treatment
      of choice for patients with relapsed chemo-sensitive intermediate grade lymphoma,
      but its role in the treatment of low-grade lymphomas and in selected patients in
      first remission remains controversial. METHODS: A large number of clinical trials
      have evaluated the role autologous SCT in both low grade and intermediate grade
      non-Hodgkin's lymphomas (NHL). These studies have attempted to evaluate the role
      of high dose therapy with stem cell support in comparison to more conventional
      chemotherapy approaches. Studies have also focused on methods to assess whether
      contaminating tumor cells are contained with the stem cell collection and whether
      this has impact on outcome. With an increased number of patients now long term
      survivors, additional studies are focusing on long term complications and in
      particular the emergence of secondary malignancies. RESULTS: Virtually all
      patients now receive peripheral blood stem cells rather than bone marrow as a
      source of stem cells. The role of purging of residual tumor cells remains
      controversial and no randomized trial has been published to date that could
      evaluate the clinical utility of cell manipulation to attempt to remove
      contaminating lymphoma cells. Secondary leukemia is emerging as a major source of
      long-term morbidity and mortality after autologous stem cell transplantation.
      CONCLUSION: Autologous SCT is associated with improved outcome in patients with
      relapsed intermediate grade lymphoma and most likely prolongs disease free
      survival in patients with low grade NHL. Morbidity and mortality of the procedure
      is low and major efforts are being made to attempt to decrease the major causes
      of failure, which remain disease relapse and occurrence of secondary
      malignancies.

PMID- 12194718
TI  - Long-term follow-up of patients with CLL treated with allogeneic hematopoietic
      transplantation.
AB  - BACKGROUND: We investigated the long-term outcome of allogeneic stem-cell
      transplantation after myeloablative conditioning regimen as treatment for
      patients with chronic lymphocytic leukemia. METHODS: Patients were eligible for
      our study if they were refractory or failed a prior response to fludarabine. The
      conditioning regimen consisted of high-dose CY 60 mg/kg daily for 2 days and
      fractionated TBI. One patient received BEAM because of prior radiation. GvHD
      prophylaxis consisted of CYA or tacrolimus and MTX in the majority of patients.
      RESULTS: Twenty eight patients were treated. nineteen had disease that was
      refractory to fludarabine. The median number of prior chemotherapy regimens per
      patient was 3. Twenty had HLA-identical donors and one had a one-Ag mismatched
      sibling donor. Seven patients had a matched unrelated transplant. The median
      follow-up time for the surviving patients was 66 months. By univariate analysis,
      chemosensitivity was the only factor that predicted a better outcome. For the
      chemosensitive patients, the overall survival was 78%, compared with 31% for
      those with refractory disease (P = 0.05). Progression-free survival at 5 years
      was 78% for the chemosensitive and 26% for those who were refractory to
      conventional chemotherapy at the time of transplantation (P = 0.03). Three
      patients (11%) died within 100 days of transplant. The actuarial risk of acute
      Grade II-IV GvHD was 49%. Only one patient developed acute Grade III GvHD.
      CONCLUSION: Allogeneic transplantation is probably curative for a subset of
      patients with chronic lymphocytic leukemia. Patients should be considered for
      clinical trials involving allogeneic transplantation at an earlier stage prior
      acquiring chemorefractoriness.

PMID- 12194719
TI  - Autologous and allogeneic transplantation for aggressive NHL.
AB  - BACKGROUND: Intermediate- and high-grade NHL are generally chemosensitive
      diseases with high initial response rates to combination chemotherapy. Dose
      intensification via autologous and allogeneic transplantation provides viable
      treatment options in specific clinical settings. Currently, autologous
      transplantation is the standard of care for relapsed but chemosensitive
      aggressive B-cell NHL. However, tools such as the International Prognostic Index
      allow risk-adapted analyses, and show that the magnitude of benefit from
      autologous transplantation differs in lymphoma subsets. METHODS: Low-risk
      patients appear to do well regardless of salvage approaches, whereas high-risk
      patients have suboptimal outcomes with autologous transplantation. In high-risk
      patients, high-dose chemotherapy with autologous stem-cell transplantation has
      been examined as part of initial therapy, with long-term data promising but still
      evolving. DISCUSSION: A significant concern with autologous transplantation in
      aggressive and high-grade NHL is the risk of graft contamination with tumor
      cells. Several investigators have demonstrated the presence of malignant cells in
      both BM and PBSC, although the clonagenic potential of such cells is unclear.
      Allogeneic stem-cell transplantation has several potential advantages over
      autologous transplantation for NHL,including procurement of an uncontaminated
      stem-cell graft, GvL effects, and the elimination of hematopoietic stem-cell
      damage and consequent secondary leukemia. RESULTS: The ideal application of
      allogeneic transplantation in aggressive and high-grade lymphomas is still
      unclear; but the lower relapse rates demonstrated in several comparisons of the
      two approaches make this an exciting area to pursue. Finally, non-myeloablative
      stem-cell transplantation may broaden the use of allogeneic transplantation by
      lowering regimen-related mortality while capitalizing on GvL.

PMID- 12194720
TI  - Hematopoietic stem-cell transplantation for Hodgkin's disease (HD): current
      status.
AB  - Not all patients with Hodgkin's disease (HD) respond to standard chemotherapy
      and/or radiation, and hematopoietic stem-cell transplantation has been gaining
      increasing acceptance in the management of HD. Phase II and, to a lesser extent,
      phase III studies of high-dose chemotherapy and autologous stem cell
      transplantation carried out at multiple institutions worldwide have proven the
      feasibility of the procedure and provided extended progression-free survival (and
      possibly cure) in a sizable number of patients with relapsed or refractory HD.
      Prognostic factors have been identified by multiple investigators (with response
      to chemotherapy being the most impressive one) and may ultimately allow a risk
      adapted strategy. While early and late treatment-related morbidity and mortality
      remains an issue, with current supportive care modalities most patients tolerate
      this procedure with only minor or manageable complications. Disease recurrence
      remains a problem in many patients, and this can unfortunately occur as late as
      six or seven years after a seemingly successful transplant. New chemotherapeutic
      agents and strategies (such as post-transplant maintenance and possibly
      immunomodulation) will be required to successfully tackle this issue. Allogeneic
      stem-cell transplantation from HLA-compatible donors has yielded largely
      unsatisfactory results in the published studies in the literature, despite
      favorable results in a small minority of patients. Recently, however, newer
      approaches and strategies (such as the introduction of reduced-intensity, purine
      analog-based conditioning regimens and possibly cellular immunotherapy in the
      form of donor lymphocyte infusions) have provided very encouraging early results
      and seem to brighten the outlook for this procedure.

PMID- 12194721
TI  - Intensive chemotherapy with hematopoietic stem-cell support for children with
      recurrent or refractory NHL.
AB  - BACKGROUND: Children with refractory or recurrent NHL are generally thought to
      have a poor prognosis. Those with chemosensitive disease are usually considered
      for an intensification phase, with either autologous or allogeneic hematopoietic
      stem-cell transplantation (HSCT). METHODS: From 1990 to 2001 we performed 24
      HSCTs in 22 children with refractory (n = 8), recurrent (n = 13), or high-risk in
      first CR (n = 1) NHL. Among the HSCTs, 19 were autologous and five were
      allogeneic. RESULTS: In two children, allogeneic HSCT was performed after failing
      autologous HSCT. The histologic subtypes comprised large cell, (n = 13),
      Burkitt's lymphoma (n = 5) and lymphoblastic (n = 4). Among the cases of primary
      relapse, 10 occurred during therapy and three occurred after completing initial
      therapy. Among the 22 children in this series, two died of transplant-related
      toxicity and nine died of progressive disease or relapse after transplant. Among
      the 11 children who are alive and disease-free, 10 had non-lymphoblastic
      histology and one had lymphoblastic disease; one relapsed after autologous HSCT,
      but was successfully salvaged with multi-agent chemotherapy and involved-field
      irradiation. Among the 22 initial transplanted cases, 10 of 19 children with
      chemosensitive disease before transplantation and one of three with
      chemoresistant disease are currently alive and disease-free. DISCUSSION:
      Intensive chemotherapy followed by hematopoietic stem-cell support is an
      effective strategy for children with chemosensitive recurrent non-lymphoblastic
      NHL.

PMID- 12194722
TI  - The choice of allogeneic or autologous hematopoietic transplantation for NHL.
AB  - NHL constitutes the sixth most common malignancy diagnosed in the USA every year,
      accounting for approximately 24,400 deaths. Although a subset of patients can be
      cured with chemotherapy or radiation therapy, the outlook is generally poor for
      patients with refractory or recurrent disease. High-dose therapy supported by
      both autologous and allogeneic transplantation has been widely studied in this
      group of patients. Autologous transplantation may be considered standard therapy
      for patients with diffuse large-cell NHL in chemotherapy-sensitive relapse.
      Selected categories of patients with other histologic subtypes may also benefit
      from this strategy. Allogeneic transplantation using high-dose myeloablative
      conditioning regimen is an effective, yet hazardous approach. A GvL effect leads
      to a lower rate of disease recurrence than occurs with autologous transplants,
      but this benefit is offset by higher risk of treatment related mortality. The
      recent use of less toxic non-myeloablative conditioning regimens for allogeneic
      transplantation has reduced the risk of transplant-related mortality, allowing
      this approach even in older or medically infirm patients. Nonablative allogeneic
      transplants are a promising strategy, particularly for patients with indolent
      lymphoid malignancies.

PMID- 12194723
TI  - Storage of blood for in vitro generation of dendritic cells.
AB  - BACKGROUND: Since the development of techniques to cultivate DC from peripheral
      blood, there has been a great deal of interest in the use of these cells in
      immunotherapeutic strategies. In a clinical setting, delays often occur between
      when blood is drawn and when it is processed. We therefore investigated the
      effect of overnight storage on the yield, morphology and phenotype of DC cultured
      from the peripheral blood of healthy volunteers. METHOD: Blood was processed
      either immediately, or after storage for 24 h in the fridge (4 degrees C) or at
      room temperature (RT, 20 degrees C). Samples were compared for starting cell
      number, DC yield and characteristics (morphology and phenotype). RESULTS: The
      number of PBMC that could be obtained was significantly lower from the
      refrigerated samples compared with both the freshly processed sample and that
      stored at RT. Samples processed after overnight storage at RT yielded cells
      morphologically identical to DC cultured from freshly processed samples. Only
      when samples were both stored and processed cold did the cultured cells not have
      typical DC morphology. DC cultured from the refrigerated samples showed a
      significant reduction in MHC II expression compared with samples processed fresh
      or stored at RT. This expression increased slightly when the sample was first
      warmed. Total DC yield and the percentage yield of cultured DC was not
      significantly different for any of the groups. DISCUSSION: We conclude that, if
      immediate processing of blood for in vitro generation of DC is not possible,
      samples should be stored at room temperature (approximately 20 degrees C).

PMID- 12194724
TI  - Enhanced expansion and maturation of megakaryocytic progenitors by fibronectin.
AB  - BACKGROUND: Megakaryopoiesis occurs as a result of a complex interaction between
      hemopoietic cells, stromal cells, hemopoietic growth factors and extracellular
      matrix (ECM). Megakaryocyte growth and development factor (MGDF) or
      thrombopoietin is the main growth factor that induces megakaryocyte commitment.
      The role of adhesion proteins in the generation of megakaryocytic progenitors has
      not been well studied. METHODS: We isolated CD34(+) cells from umbilical cord
      (UC) blood and cultured them in serum-free medium containing IL-3, IL-6, SCF and
      MGDF, with or without fibronectin. Cultures were sampled at Days 4 and 8 for cell
      count, immunophenotyping by flow cytometry, and megakaryocyte colony-forming
      units (CFU-Mk) assay. RESULTS: Fibronectin in synergy with MGDF increased both
      total and CD34(+) cell count. Immunophenotyping of the CD34(+) and CD34(-) cells
      showed that the percentage expression of CD61 and CD41a on CD34(-) cells was
      increased by fibronectin compared with CD34(+) cells by Day 8 of culture. The CFU
      Mk assay confirmed that fibronectin increased generation of megakaryocytic
      progenitors by 2.4-fold by Day 8 of culture, but the absolute number was less
      than that of Day 4 culture. The cells in the CFU-Mk colonies derived from culture
      containing fibronectin were larger than those from cytokine-only culture.
      CONCLUSION: It was concluded that the addition of fibronectin to the culture
      system enhanced MGDF, induced ex vivo expansion of megakaryocytic progenitors
      from CD34(+) cells, as well as increasing their maturation towards later stages
      of megakaryocyte differentiation.

PMID- 12194725
TI  - 3D culture of murine hematopoietic cells with spatial development of stromal
      cells in nonwoven fabrics.
AB  - BACKGROUND: The in vivo hematopoietic microenvironment is composed of stromal
      cells and extracellular matrix in a 3D configuration. We have created a 3D
      microenvironment in vitro, employing spatial development of stromal cells in a
      nonwoven fabric porous carrier, Fibra-cel (FC). We compared its performance with
      that of a 2D microenvironment. METHODS: Primary murine BM cells were inoculated
      on the layers of stromal cells prepared in FC (3D) or on a dish (2D) and cultured
      for 7-21 days. The hematopoietic cells harvested from the cultures were evaluated
      by colony-forming unit (CFU) assay and transplantation to sub lethally irradiated
      mice. RESULTS: The maximum stromal cell concentration in the 2D culture was
      higher than that in the 3D culture. However, the hematopoietic cell concentration
      in the 3D culture was kept at a higher level than that in the 2D culture. The
      number of CFU-mix increased five times during 3D cultivation, but decreased in
      the 2D culture. The engraftment percentage of 3D cultured cells was comparable
      with that of fresh cells, and markedly higher than that of 2D cultured cells.
      DISCUSSION: The 3D culture constructed with FC and stromal cells was clearly
      superior to 2D culture because hematopoietic progenitor cells were expanded
      without the addition of cytokines and the content of hematopoietic stem cells was
      maintained.

PMID- 12194726
TI  - In vitro interactions between gamma deltaT cells, DC, and CD4+ T cells;
      implications for the immunotherapy of leukemia.
AB  - BACKGROUND: Gamma deltaT cells contribute to immune defense against infectious
      organisms and some malignancies, but the process of activation and proliferation
      of these cells is not well understood. It is known that the immune response of
      gamma deltaT cells is not MHC-dependent, but is likely based on direct
      recognition of surface peptides and non-peptide ligands. This study examined
      whether DCs and CD4(+) T cells can participate in the activation of gamma deltaT
      cells. METHOD: Peripheral blood gamma deltaT cells were co-cultured with CD34
      derived autologous DCs and CD4(+) T cells using contact-dependent cultures and
      transwell systems. Proliferation, immunophenotyping, and cytotoxicity assays
      determined the extent of gamma deltaT cell proliferation and cytotoxicity.
      RESULTS: Human gamma deltaT cells expanded 221.3 +/- 76-fold in cultures with
      DCs, and 165.7 +/- 76.6-fold with CD4(+) T-cells alone. Proliferation was
      enhanced (1949.8 +/- 261.3-fold) when gamma deltaT cells were cultured with both
      DC and CD4(+) T cells. Proliferation was contact-dependent, and resulted in the
      expansion of V delta1+ or V delta2+ cells cytotoxic against several leukemic cell
      lines, but not against allogeneic PHA-induced lymphoid blasts. Ligation of the T
      cell receptor with anti-pan-delta Ab significantly up-regulated cytotoxicity
      against K562, KBM-5 and KG1a, and normal BM, but not against Molt-4, allogeneic
      EBV-transfected B cells and allogeneic PHA-blasts. Minimal cytotoxic activity was
      shown against allogeneic marrow colony-forming units granulocyte-macrophage and
      erythrocyte colony-forming units. CONCLUSION: DCs can participate in the
      activation of gamma deltaT cells against specific autologous targets, and
      cytotoxicity can be enhanced by further stimulation via the T-cell receptor.

PMID- 12194727
TI  - Maintenance of breast size reduction after mastoplasty and switch to a protease
      inhibitor-sparing regimen in an HIV-positive woman with highly active
      antiretroviral therapy-associated massive breast enlargement.
AB  - Fat distribution disorders are among the most frequent side effects of
      antiretroviral treatment. The pathophysiologic mechanism(s) for these events
      remains unclear, and a casual link to a specific drug or class of drugs is
      uncertain. The physical changes associated with the lipodystrophy syndrome can be
      divided into three major types: lipoatrophy or fat wasting; lipohypertrophy or
      fat accumulation; and mixed forms with atrophy and hypertrophy coexisting in
      different body regions. Fat accumulation can occur in one or more of several
      areas including dorsal-cervical and abdominal regions and breasts. Withdrawal of
      antiretroviral therapy does not seem to influence the stabilized lesions
      significantly, and no one of the therapeutic strategies adopted so far was
      capable to achieve substantial improvements. Here we describe the successful and
      lasting treatment of a massive and movement/posture-hampering breast hypertrophy
      with reductive mastoplasty.

PMID- 12194728
TI  - The case for comprehensive sex education.
AB  - Half of all new human immunodeficiency virus (HIV) infections in the United
      States and two thirds of all sexually transmitted diseases (STD) occur among
      young people under the age of 25. It is estimated that by the end of high school,
      nearly two thirds of American youth are sexually active, and one in five has had
      four or more sexual partners. Despite these alarming statistics, less than half
      of all public schools in the United States offer information on how to obtain
      contraceptives and most schools increasingly teach abstinence-only-until-marriage
      (or "abstinence-only") education. There is little evidence that abstinence-only
      programs are successful in encouraging teenagers from delaying sexuality activity
      until marriage, and consequently, avoiding pregnancy, or STD or HIV infection.
      Comprehensive sex education, which emphasizes the benefits of abstinence while
      also teaching about contraception and disease-prevention methods, has been proven
      to reduce rates of teen pregnancy and STD infection.

PMID- 12194729
TI  - Evaluation and treatment of the HIV/HCV coinfected patient: a case history and
      discussion.
AB  - Declining rates of morbidity and mortality related to opportunistic infections in
      the era of highly active antiretroviral therapy (HAART) have led to a new focus
      on hepatitis C (HCV). Several studies suggest that the natural history of HCV is
      accelerated in patients with HIV infection. Recent literature highlights higher
      rates of fibrosis progression and increasing rates of morbidity and mortality
      related to end-stage liver disease. As a result, more and more clinicians are
      turning their attention to the evaluation and management of hepatitis C in an
      effort to prevent or slow down the progression to advanced liver disease. The
      following case history illustrates many of the complicated steps in the
      evaluation process of these patients. Several important issues are discussed,
      such as the rationale in performing a liver biopsy, when to initiate treatment,
      drug interactions, and adverse effects of therapy.

PMID- 12194732
TI  - Counterfeit Serostim.

PMID- 12194730
TI  - Long-term treatment with subcutaneous T-20, a fusion inhibitor, in HIV-infected
      patients: patient satisfaction and impact on activities of daily living.
AB  - T-20 is a novel antiretroviral agent that inhibits the fusion of human
      immunodeficiency virus (HIV) with target cell membranes. It is delivered by self
      administered, twice-daily, subcutaneous injections. The impact of this mode of
      administration on patients' ability to conduct normal activities of daily living
      (ADL) and comply with a T-20 treatment regimen was assessed as part of a 48-week,
      phase 2 trial (T20-205). Patients' opinions on the impact of T-20 on ADL, ease of
      use of T-20, and choice to continue with T-20 were assessed by two questionnaires
      completed at baseline and week 48 (or study withdrawal). ADL were measured using
      a Likert-type scale based on established instruments with questions added to
      assess HIV-specific issues. Seventy previously treated patients received T-20 in
      combination with an average of five oral antiretroviral agents. Relative to other
      HIV/AIDS drugs, T-20 had little impact on ADL, with the majority of patients (54%
      96%) agreeing (somewhat or strongly) that subcutaneous injections had not limited
      ADL. Patients found the injections relatively easy to perform with more than 47%
      of patients stating that each aspect of the injections (ease of injection,
      storage, reconstitution, and disposal of sharps) were very easy or easy. If
      medically indicated, 98% of patients stated that they would choose to continue
      with T-20. The most common reasons for this were the perceived effectiveness of T
      20 and lack of side effects. In conclusion, the need to deliver T-20 via twice
      daily subcutaneous injections was not considered an important barrier by HIV
      positive patients seeking improvement or stabilization of their condition.

PMID- 12194733
TI  - Haematospermia: in the context of a genitourinary medicine setting.
AB  - Haematospermia should be taken more seriously. Although it is usually benign and
      self-limiting, it provokes great anxiety in patients. Malignancy is generally
      rare, but it should particularly be considered in older patients (40 years old or
      above). Recent investigative modalities, especially non-invasive, have made
      diagnosis feasible in most cases. What will constitute a reasonable approach to
      the problem of haematospermia in the context of a genitourinary medicine setting?
      A detailed history and physical examination, including genital and rectal
      examination, would be necessary. Initial investigations could include screening
      for STIs, urine examination and full blood count. Few patients will need further
      investigations, which will depend on the findings in patients' history and
      examination as well as the nature of the bleeding. Patients should be given a
      detailed explanation of their condition, and a plan of management and follow up
      should be made clear to them. Treatment depends on the underlying cause but often
      simply involves reassurance. Referral to a urologist may include patients with
      recurrent or persistent haematospermia, those with associated symptoms and
      patients who are 40 years old or above.

PMID- 12194734
TI  - Facts and myths on recurrent vulvovaginal candidosis--a review on epidemiology,
      clinical manifestations, diagnosis, pathogenesis and therapy.
AB  - Approximately three-quarters of all women will experience an episode of
      vulvovaginal candidosis at least once in their life and 5-10% of them will have
      more than one attack. Women suffering from three to four attacks within 12 months
      will be diagnosed with recurrent vulvovaginal candidosis (RVVC). This review
      covers the large number of proposed aetiological factors for RVVC. The diagnosis
      of the condition made by conventional means by health providers is often false
      and is also often misdiagnosed by the affected woman herself. The review covers
      various methods of diagnosing RVVC and the current knowledge on potential
      pathogenetic mechanisms proposed for genital candida infections. Treatment of
      RVVC, including local and systemic antimicrobial therapy and behaviour
      modification to decrease the risk of recurrences, are discussed. Recent knowledge
      on drug resistance in candida is also included.

PMID- 12194735
TI  - Sensitivity evaluation of the Gen-Probe AMP-CT assay by pooling urine samples for
      the screening of Chlamydia trachomatis urogenital infection.
AB  - The sensitivity of two urine pool sizes versus individual testing, to detect
      Chlamydia trachomatis urogenital infection, was evaluated using the Gen-Probe AMP
      CT assay. Thirty-three (33) known polymerase chain reaction (PCR) positive urine
      specimens were combined with 231 fresh first-catch urine (FCU) samples in 33
      groups of four and 33 groups of eight, to make up 4X and 8X pooled samples,
      respectively. Gen-Probe AMP-CT assay was performed on pools as well as on
      individual samples at the same time. For the discrepant cases, the known positive
      samples were diluted 1:4 and 1:8 using the manufacturer's dilution buffer and
      were retested. Additional positive specimens found among fresh FCU samples were
      also tested by the Amplicor-PCR assay to confirm their positivity. The
      sensitivities of 8X pooling, 4X pooling and individual testing were 86.5%, 94.3%
      and 91.9%, respectively. The Gen-Probe AMP-CT assay applied to a 4X urine pooling
      model was highly sensitive and may be useful for a population based screening
      programme.

PMID- 12194736
TI  - Availability of dental services for patients with blood-borne viruses.
AB  - Dental practitioners were surveyed, using a self-completed postal questionnaire,
      to assess their attitudes to managing patients with blood-borne viruses (BBV) and
      to identify dental services available for such patients in North Nottinghamshire.
      Questionnaires were completed by 79 (65.3%) of the 121 practitioners from 43
      (82.7%) of the 52 study practices. Previous BBV experience was reported by 44
      (55.7%), 31 (39.2%), 20 (25.3%) respondents for hepatitis B (HBV), hepatitis C
      (HCV), HIV, respectively. Over two-thirds would maintain existing patients with
      subsequently diagnosed BBV on their lists, approximately one-third would accept
      new BBV patients. Risk factors for BBV of homo/bisexuality and injecting drug use
      were not asked by 71 (89.9%) and 49 (62.0%) practitioners, respectively.
      Universal precautions were employed by 67 (84.8%) practitioners regardless of the
      patient's status and by seven practitioners for known BBV patients. The advice of
      the General Dental Council, British Dental Association, and the use of universal
      precautions are discussed.

PMID- 12194737
TI  - Frequency of herpes simplex virus, cytomegalovirus and human papillomavirus DNA
      in semen.
AB  - Herpes simplex virus (HSV-2) and cytomegalovirus (CMV) infections produce brain
      damage in the newborn, and human papillomavirus (HPV) plays a role in cervical
      carcinogenesis. To assess the frequency of herpes virus and HPV in semen and its
      role in transmission, semen from 111 male partners of women with histologically
      detected genital HPV infection was analysed for HSV, CMV and HPV infection. We
      used cell culture to detect HSV and CMV, and polymerase chain reaction (PCR) for
      HPV. Virological findings in the sperm were correlated to the presence or absence
      of HPV-associated genital lesions and to the viral type. Viral cultures yielded
      HSV-2 DNA in 9% and CMV DNA in 6.3% of cases. No correlation was established with
      a history of clinically apparent infection for HSV. HPV-DNA was detected in 23.4%
      of semen by PCR techniques: in 48% of subjects with urethral lesions, in 22% of
      patients with penile lesions, in 2% of patients without HPV-associated lesions.
      HPV-DNA type 16 was detected in 3.6% of cases. Patients with a positive HPV semen
      sample and penile or urethral lesions had the same HPV type detected in the two
      specimens. The study shows a high detection of clinically inapparent HSV and CMV,
      but does not confirm high HPV prevalence in semen from men without detectable
      lesions. Our study also suggests that the mechanism for semen contamination by
      HPV is the exfoliation of infected cells from urethral lesions during semen
      ejaculation, and probably, by abrasion from penile lesions. This could result in
      the contamination of semen used in assisted reproductive technology.

PMID- 12194738
TI  - Mother to child human immunodeficiency virus (HIV) transmission: what HIV
      infected women think. Our experience in Rome, Italy.
AB  - OBJECTIVES: To investigate the knowledge of the risk of HIV vertical transmission
      as well as the feeling about the new therapy in reducing that rate. METHODS: We
      included 152 HIV-infected women. A self reported questionnaire was administered
      from September to December 2000. RESULTS: About the risk rate of transmitting HIV
      to their baby, 21 (13.8%) women indicated 100%; 67 (44.1%) 50-80%; 35 (23%) 10
      50% and only 22 women (14.5%) answered the correct value of less than 5%.
      Regarding the effect of highly active antiretroviral therapy, 82 women (53.9%)
      considered therapy effective in reducing vertical HIV transmission, while 63
      women (41.4%) considered therapy powerless in preventing mother to child HIV
      transmission. Any statistically significant difference in sociodemographic,
      clinical, viroimmunological characteristics and antiretroviral therapy emerged
      between the groups. CONCLUSIONS: Our data highlight the importance of providing
      appropriate counselling about perinatal HIV transmission to all childbearing age
      HIV infected women.

PMID- 12194739
TI  - Low prevalence of antiretroviral resistance among persons recently infected with
      human immunodeficiency virus in two US cities.
AB  - Resistance testing for treatment-naive, recently HIV-infected persons is not
      currently recommended; its clinical value will depend on the prevalence of
      resistance-associated mutations among recently infected persons. To estimate this
      prevalence, specimens were collected during 1997-1999 in Seattle and Los Angeles
      from drug-naive, recently HIV-infected persons. HIV-1 protease and reverse
      transcriptase (RT) RNA sequences were amplified from plasma by RT-polymerase
      chain reaction (RT-PCR), sequenced, and analysed. Of 69 patients, five (7%) had
      resistance-associated mutations: three (4%) had primary mutations associated with
      resistance to nucleoside reverse transcriptase inhibitors (NRTI) or non
      nucleoside-RTIs, and three patients (4%) had secondary NRTI mutations. No primary
      mutation associated with resistance to protease inhibitors was observed. Mean age
      of the five persons with resistance-associated mutations (38 years) was higher
      than that of the 64 persons without resistance-associated mutations (31 years,
      P=0.04). The findings suggest that the prevalence of resistance-associated
      mutations among persons recently infected with HIV in these cities is low.

PMID- 12194740
TI  - Diagnosis of bacterial vaginosis on self-collected vaginal tampon specimens.
AB  - A vaginal tampon specimen was previously shown to be suitable for the molecular
      diagnosis of non-ulcerative sexually transmitted infections (STIs). Different
      tampon fluid preparations were evaluated for the diagnosis of bacterial vaginosis
      (BV). Women with pregnancy related problems were enrolled. Two observers
      evaluated the different tampon fluid preparations and vaginal smears collected
      during speculum examination using the Nugent score. Using the Amsel criteria, 21%
      of the 84 women enrolled were diagnosed with BV. Results of the tampon fluid
      preparations and vaginal smears showed excellent agreement for both observers
      (Spearman >0.80). The overall sensitivity and specificity was 91.7% (95% CI: 81.6
      96.5) and 79.3% (95% CI: 67.2-87.8), respectively, using the Amsel criteria as
      reference standard. The tampon provides a specimen for the combined diagnosis of
      non-ulcerative STIs and BV. This non-invasively collected specimen may facilitate
      self-initiated testing and population-based studies as well as longitudinal
      studies that are necessary to gain insight in the epidemiology of BV related to
      STIs and HIV.

PMID- 12194741
TI  - High incidence of treatment failure of Neisseria gonorrhoeae isolates to
      ciprofloxacin in male gonococcal urethritis in Delhi.
AB  - Several treatment failures and widespread antimicrobial resistance to
      ciprofloxacin have been documented, subsequent to its initial recommendation in
      1989 as a single dose alternative therapy for gonorrhoea. Still, it continues to
      be part of various treatment schedules in National STD control guidelines
      including India. This prompted us to study the current status of this drug in the
      treatment of gonorrhoea. Thirty-five male patients with gonococcal urethritis
      were included in the study. The susceptibility to penicillin, tetracycline,
      ciprofloxacin and ceftriaxone was determined by Kirby-Bauer disc diffusion method
      and minimum inhibitory concentration (MIC) of ciprofloxacin by agar plate
      dilution method. The clinical and bacteriological response was assessed on day 5
      after treatment with single dose ciprofloxacin, 500 mg. The sensitivity pattern
      of Neisseria gonorrhoeae was observed to be: ceftriaxone 100%, azithromycin 100%,
      tetracycline 65.7%, penicillin 40% and ciprofloxacin 5.7% by disc diffusion
      method. The MIC for ciprofloxacin was below 0.06 microg/mL (sensitive) in one
      (2.5%) isolate only. On the fifth day a large number of treatment failures
      (88.5%) were seen with ciprofloxacin while none was noted one week after re
      treatment with ceftriaxone. The location of endemic quinolone-resistant N.
      gonorrhoeae (QRNG) in New Delhi has increased alarmingly, resulting in an
      extremely high proportion of therapeutic failures, and thus requiring appropriate
      alterations in the presently recommended treatment regimens.

PMID- 12194742
TI  - Pelvic inflammatory disease in the People's Republic of China: aetiology and
      management.
AB  - OBJECTIVES: To study the causes of pelvic inflammatory disease (PID) in Shenyang,
      Northeastern China, and to assess the efficacy of the syndromic management
      flowchart for PID recommended by World Health Organization (WHO). METHODS: 200
      outpatients with PID attending Gynaecologic Clinic of No. 1 and No. 2 hospital of
      China Medical University in Shenyang, and 155 control women without symptoms
      underwent pelvic examination, and were tested for Chlamydia trachomatis (CT),
      Neisseria gonorrhoeae (NG), Mycoplasma hominis (MH), bacterial vaginosis (BV),
      Candida albicans (CA) and Trichomonas vaginalis (TV). RESULTS: In PID patients,
      the prevalence of MH was 26%, of BV 26%, of CT 16%, of CA 11%, of TV 4% and of NG
      2.5%. In the control population, prevalences were 5.2%, 8.4%, 0%, 5.2%, 0.7%, 0%
      respectively. MH, BV and CT were significantly more common in PID patients than
      in controls (P<0.01). One hundred and thirty-seven of the 200 patients with PID
      (68.5%) returned for follow-up. Symptoms had resolved completely in 64 (47%), and
      had improved in 68 (50%). There was no improvement in five (4%). CONCLUSIONS: The
      management protocol for female lower abdominal pain recommended by WHO is
      effective in this setting.

PMID- 12194743
TI  - Efficacy and safety of penile biopsy in a GUM clinic setting.
AB  - The UK National Guidelines on Sexually Transmitted Infections recommend penile
      biopsy in patients with persistent balanitis and balanitis of uncertain
      aetiology. Many GUM clinics perform penile biopsy. However, few studies have
      looked at the usefulness and safety of penile biopsy in a GUM clinic setting. We
      assessed the spectrum of dermatological conditions seen in a penile dermatoses
      clinic and looked at the usefulness and safety of penile punch biopsy in a GUM
      clinic setting. We reviewed the case notes of patients who attended the penile
      dermatoses clinic at the GUM department, Royal Berkshire Hospital, Reading over a
      period of 18 months. A total of 87 patients were seen in the penile dermatoses
      clinic. Their ages ranged from 17 to 73 and 70 (80%) were uncircumcised. Twenty
      four (28%) patients had biopsies and five (6%) declined. Forty-nine (56%)
      patients did not have a biopsy either because of a clinically apparent diagnosis
      (45) or lesions were close to the urethral meatus (4). Five were referred for
      circumcision and one was referred to a dermatologist. Three patients were lost to
      follow-up. Penile biopsy was performed to exclude malignancy in 17 (71%) cases
      and due to diagnostic uncertainty in seven (29%) cases. Histological diagnoses
      were consistent with initial clinical diagnoses in 17 (71%) cases. Four (17%) had
      minor complications following biopsy, two had wound dehiscence, one had bleeding
      and another had a wound infection. In conclusion, a wide spectrum of penile skin
      disorders were seen in the penile dermatoses clinic. The majority of patients had
      a clinically apparent diagnosis. The histological diagnosis was consistent with
      initial clinical diagnosis in most of the biopsied patients. The main indications
      for biopsy were to exclude malignancy and for diagnostic dilemma. Penile biopsy
      is a safe procedure with minimal complications.

PMID- 12194744
TI  - An audit of outpatient management of pelvic inflammatory disease.
AB  - Pelvic inflammatory disease (PID) is a common condition presenting to
      Genitourinary Medicine clinics in the UK. It is unclear what is the best
      therapeutic option in the outpatient setting. A clinical audit of current
      standard of care in women presenting with PID was conducted. A total of 150 women
      were diagnosed clinically during a six-month period. Chlamydia and gonorrhoea
      were identified in 30% and 4% of patients respectively. The clinical and
      microbiological cure rates of oral doxycycline and metronidazole were assessed.
      In 57% of patients their symptoms resolved, but 18% had persistent signs and
      symptoms; 25% did not attend for follow up visit. Partner notification was
      discussed in 87% of patients. With a treatment failure rate of 18% we felt it
      appropriate to change the antibiotic regimen of PID in our department.

PMID- 12194745
TI  - A case of immune reconstitution rheumatoid arthritis.

PMID- 12194746
TI  - Tamoxifen in antiretroviral-associated gynaecomastia.
AB  - Gynaecomastia arising in the context of antiretroviral therapy for HIV infection
      presents a number of challenges in diagnosis and management. We describe a thirty
      year old gay man with rapidly developing breast enlargement who was successfully
      treated with the anti-oestrogen tamoxifen.

PMID- 12194747
TI  - Spinal schwannoma as a cause of erectile dysfunction with urinary incontinence
      and groin and testicular pain.

PMID- 12194748
TI  - Anti-apoptotic Bcl-2 proteins: structure, function and relevance for radiation
      biology.
AB  - PURPOSE: Bcl-2 family members mediate anti-apoptotic signals in a wide variety of
      human cell systems. Despite its proven antiapoptotic function, several results
      indicate that overexpression of Bcl-2 is not clearly associated with increased
      radiation resistance in vitro or in vivo. The reasons for this obvious
      contradiction are not understood. MATERIALS AND METHODS: Current data on the
      function of Bcl-2 as an anti-apoptotic protein, its role for the modulation of
      radiation sensitivity in vitro and its value as prognostic marker in vivo are
      reviewed. RESULTS: Bcl-2 and related proteins are currently perceived to be the
      most important anti-apoptotic proteins. Their function is related to their
      ability to interfere with mitochondrial apoptosis pathways. Contradictory data
      have been published on the relevance of Bcl-2 and related family members for in
      vitro and in vivo tumour response. The value of Bcl-2 as a prognostic marker thus
      remains unclear. CONCLUSIONS: Although Bcl-2-related proteins are currently the
      most relevant anti-apoptotic modulators, their relevance for radiation responses
      in vivo or in vitro remain undefined. Furthermore, their determination in a
      routine clinical setting does not appear to be justified.

PMID- 12194749
TI  - Effects of mobile phone emissions on human brain activity and sleep variables.
AB  - PURPOSE: To compare the findings of the main studies that have examined the
      effects of GSM mobile phone radiofrequency emissions on human brain activity and
      sleep variables. MATERIALS AND METHODS: Fourteen published studies reporting on
      human brain electrical activity measurements during and/or after such
      radiofrequency emissions were identified and compared. CONCLUSIONS: Although, in
      general, outcomes have been inconsistent and comparison between individual
      studies is difficult, enhanced electroencephalogram alpha-band power has been
      noted in several of the studies, a phenomenon also observed in some animal
      studies. Performance decrements observed in some recent extremely low frequency
      studies are consistent with enhanced alpha-band power, highlighting the possible
      role of extremely low frequency fields associated with battery current in mobile
      phone handsets. However, more complex cognitive tasks appear to show improved
      performance in relation to mobile phone exposure. Significant cognitive effects
      have been reported using both modulated and unmodulated radiofrequency carriers.
      The possibility of putative effects being due to extremely low frequency
      demodulation is therefore unlikely. There are no obvious associations between the
      site of exposure and regions of the brain from which effects are reported or
      implied. Lastly, radiofrequency effects have been reported to occur both during
      exposure and up to 1 h or so after cessation of exposure.

PMID- 12194750
TI  - High levels of chromosome aberrations correlate with impaired in vitro radiation
      induced apoptosis and DNA repair in human B-chronic lymphocytic leukaemia cells.
AB  - PURPOSE: To investigate the relationship between the susceptibility of B-chronic
      lymphoid leukaemia (B-CLL) cells to DNA damage-induced apoptosis, the kinetics of
      DNA strand-break rejoining, and chromosome damage after exposure to ionizing
      irradiation. MATERIALS AND METHODS: Lymphocytes from B-CLL patients were gamma
      irradiated in vitro with 0.2-5 Gy and stimulated by Staphylococcus aureus cowan I
      (SAC I) for estimation of chromosomal damage. Induction of apoptosis after
      irradiation was studied in 50 patients by two methods: morphological
      characterization of apoptotic cells after fluorescent staining (Hoechst), and
      specific quantification of mono- and oligonucleosomes in cytoplasmic cell
      fractions (ELISA assay). Morphological chromosome damage was scored in the first
      cell generation after irradiation (13 patients). In parallel, the kinetics of DNA
      single-strand break rejoining were investigated by the alkaline comet assay (12
      patients). RESULTS: Ionizing irradiation did not induce apoptosis in lymphocytes
      from a subset of B-CLL patients. The results suggest that B-CLL cells resistant
      to radiation-induced apoptosis could repair DNA strand-breaks more rapidly and
      showed a higher level of chromosome aberrations than radiation-sensitive B-CLL
      cells. CONCLUSION: Each of three biological effects observed (apoptosis, kinetics
      of DNA single-strand-break repair, chromosomal damage) might be explained by
      different modifications occurring in irradiated B-CLL cells. Their convergence
      strongly suggests that resistance to apoptotic death initiation by DNA damage may
      be impeded by a rapid engaging of the DNA repair mechanisms. The higher level of
      chromosome aberrations observed in these cells suggests that the type of DNA
      repair system involved may generate inaccurate repair.

PMID- 12194751
TI  - The effect of the ratio of CD4+ to CD8+ T-cells on radiation-induced apoptosis in
      human lymphocyte subpopulations.
AB  - PURPOSE: Apoptosis occurs spontaneously in cultured human peripheral blood
      lymphocytes but is enhanced by exposure to ionizing radiation. Subpopulations of
      lymphocytes are known to have varying radiosensitivities to radiation-induced
      apoptosis. The purpose of this study was to examine the radiation-induced
      apoptotic response of CD4(+) and CD8(+) T-cells incubated as a complete
      lymphocyte population. MATERIALS AND METHODS: Using a four-colour flow-cytometry
      method, which measures annexin-V binding to phosphatidyl serine and propidium
      iodide, spontaneous and radiation-induced apoptosis was measured in the total
      lymphocyte fraction and in CD4(+) and CD8(+) T-cell subpopulations. RESULTS: It
      was found that CD8(+) T-cells were more sensitive to radiation-induced apoptosis
      than CD4(+) T-cells at doses up to 2 Gy. The yield of radiation-induced apoptosis
      in the total lymphocyte fraction decreased with increasing ratios of CD4(+) to
      CD8(+) T-cells (CD4/CD8 ratio). By manipulating the CD4/CD8 ratio within
      lymphocyte cultures, it was found that the CD4/CD8 ratio had a dramatic effect on
      the yield of spontaneous apoptosis of total lymphocytes fraction and CD4(+) T
      cells but not CD8(+) T-cells. CONCLUSION: The CD4/CD8 ratio affects the apoptotic
      response of human lymphocytes and CD4(+) T-cells.

PMID- 12194752
TI  - Radiation-induced apoptosis in the scid mouse spleen after low dose-rate
      irradiation.
AB  - PURPOSE: To elucidate the process of radioadaptation, the role of DNA-PK activity
      was examined using the scid mouse defective in DNA-PKcs. MATERIALS AND METHODS:
      The induction of apoptosis in the spleens of the C.B-17 Icr scid mouse and the
      parental mouse was studied after chronic irradiation with gamma-rays at 1.5 Gy
      (0.001 Gy min(-1) for 25 h) followed by challenge irradiation with X-rays at 3.0
      Gy (1.0 Gy min(-1) for 3 min). RESULTS: When the wild-type mouse was previously
      exposed to chronic irradiation (1.5 Gy) at a low dose-rate (0.001 Gy min(-1)),
      apoptosis induced by acute irradiation (3.0 Gy, 1.0 Gy min(-1)) was significantly
      suppressed, especially in the splenic white pulp. There was no change by acute
      irradiation after chronic irradiation in the scid mouse, although an effect was
      detected in the spleen after acute irradiation alone. CONCLUSIONS: These data
      suggest that DNA-PK activity might play a major role in the radioadaptive
      response following pre-irradiation at a low dose-rate.

PMID- 12194753
TI  - Effect of dose and dose-distribution in damage to the kidney following abdominal
      radiotherapy.
AB  - PURPOSE: To define the effects of abdominal radiotherapy on the kidney with
      regard to dose-distribution parameters. MATERIALS AND METHODS: Ninety-one
      patients with abdominal radiotherapy were included in the study, and the minimum
      follow-up was 1 year. Conventional fractionation, 5 x 1.8-2.0 Gy week(-1) to
      total doses of 30.6-62.5 Gy, was employed. Assessment of organ function was
      performed before, immediately after, and at 6 months and 1 year after
      radiotherapy. In cases with a significant radiation response at 1 year,
      subsequent follow-ups were done at 6-month intervals. Documented parameters
      included clinical examination, static and sequential scintigraphy of the kidneys,
      abdominal computed tomography, and sonography. RESULTS: Twenty-one patients (23%)
      developed a reduction in kidney function detected by static scintigraphy. Only in
      15 of these patients was impairment of renal function observed by sequential
      scintigraphy. The contribution of the irradiated kidney to overall renal function
      decreased progressively to 34-40% by the third year after treatment. Hypertension
      was seen in two patients. No changes were found in laboratory parameters. ED(50)
      for scintigraphic changes decreased from 27 Gy for 10% of the volume to 7.6 Gy
      for 100%. ED(5) were in the range of 3-6 Gy, and this was independent of volume.
      CONCLUSIONS: Sophisticated imaging techniques allow the identification of
      radiation effects in partial volumes of the kidneys. A dose-response relationship
      in relation to the volume of kidney irradiated can thus be established for
      scintigraphic changes. As in a number of other organs, such changes do not relate
      directly to loss of renal function due to the reserve capacity of unirradiated
      kidney tissue.

PMID- 12194754
TI  - Study of the gonocyte cell cycle in irradiated TP53 knockout mouse foetuses and
      newborns.
AB  - PURPOSE: To investigate the role of p53 in gonocyte cell-cycle arrest in rodents
      with or without radiation exposure. MATERIALS AND METHODS: Pregnant p53 (+/-)
      mice, mated with p53 (-/-) males, were exposed to (137)Cs gamma-rays at day 18
      postcoitum (p.c.) at doses ranging from 1.5 Gy to 3 Gy. The gonocyte cell cycle
      was studied in p53 (-/-) male foetuses and newborns after BrdU incorporation and
      DAPI staining, and compared with those of p53 wild-type animals. RESULTS: The
      proliferation of gonocytes in wild-type mice is normally arrested between day 16
      p.c. and birth, a period when p53 is strongly expressed in gonocytes; p53 high
      expression is prolonged in all gonocytes after 3 Gy irradiation. In p53 (-/-)
      mice, this period of gonocyte cell-cycle arrest is not modified, compared with
      wild-type mice. It is also prolonged after a 3 Gy exposure. CONCLUSION: Two
      hypotheses are proposed. Either p53 is not involved in the control of gonocyte
      cell-cycle arrest in control and irradiated mice, or its role is redundant in
      this process.

PMID- 12194755
TI  - Anti-inflammatory effect of low-dose X-irradiation and the involvement of a TGF
      beta1-induced down-regulation of leukocyte/endothelial cell adhesion.
AB  - PURPOSE: Low-dose radiotherapy (LD-RT) is known to exert an anti-inflammatory
      effect, but the underlying radiobiological and immunological mechanisms remain
      elusive. In recent studies, we observed a reduced adhesion of peripheral blood
      mononuclear cells (PBMC) to endothelial cells (EC) after LD-RT (0.3-0.7 Gy). This
      shows that this treatment affects the initial steps of the inflammatory response.
      To explore the role of inflammatory mediators in this process, we investigated
      the expression of Transforming growth factor beta(1) (TGF-beta(1)) and
      Interleukin 6 (IL-6) after LD-RT. MATERIALS AND METHODS: EC were grown to
      subconfluence and irradiated with single-dose LD-RT. Twenty-hours after
      irradiation, EC were treated with IL-1beta for 4 h and then incubated with
      peripheral blood mononuclear cells (PBMC). Adherent PBMC were counted when using
      light microscopy. Expression of the cytokines TGF-beta(1) and IL-6 was measured
      by ELISA, and mRNA levels were analysed by the RNAse-protection assay (RPA).
      Surface expression of E-selectin was quantified by flow cytometry. RESULTS: A
      relative minimum of adhesion was observed after LD-RT between 0.3 and 0.7 Gy.
      This was paralleled by an expression maximum of TGF-beta(1) and IL-6, as shown by
      protein and mRNA levels, respectively. Neutralization of TGF-beta(1) by
      monoclonal antibodies, but not of IL-6, increased PBMC adhesion to EC nearly to
      control levels. In addition, fluorescence activated cell sorter (FACS) analysis
      of irradiated EC demonstrated a down-regulation of E-selectin in the same dose
      range. CONCLUSION: Low-dose X-irradiation between 0.3 and 0.7 Gy induced a
      relative maximum of TGF-beta(1) production by stimulated EC. This results in a
      down-regulation of leukocyte/PBMC adhesion and may contribute to the anti
      inflammatory effect of LD-RT.

PMID- 12194756
TI  - Preferential radiosensitization in p53-mutated human tumour cell lines by
      pentoxifylline-mediated disruption of the G2/M checkpoint control.
AB  - PURPOSE: There is evidence that the duration of the G2/M delay following
      irradiation is correlated with cell survival. We studied the radiosensitizing
      potential of pentoxifylline (PTX) and the PTX-mediated modulation of cell-cycle
      progression dependent on the p53 status of various human tumour cell lines.
      MATERIALS AND METHODS: The cellular radiosensitivity of human MCF-7 (wild-type
      p53) and HT-29 (p53-defective) tumour cells, which were exposed to PTX (2 mM)
      immediately after gamma-irradiation was determined by colony forming assay. The
      influence on cell cycle progression after irradiation (6 Gy) was assessed by flow
      cytometric analysis using p53 wild-type MCF-7 and HPR600 cells, and p53-defective
      HT-29 and WiDr cells. RESULTS: Clonogenic survival assays up to 8 Gy demonstrated
      that p53-defective HT-29 cells (sensitizer enhancement ratio [SER]=1.54) were
      sensitized by PTX (2 mM) to a significantly higher degree than p53 wild-type MCF
      7 (SER=1.14) cells. Exposure of irradiated (6 Gy) cells to PTX (2 mM) resulted in
      abrogation of the radiation-induced G2/M arrest in the p53-defective HT-29 and
      WiDr cells, whereas the p53 wild-type-expressing MCF-7 and HPR600 cells showed
      less significant impairment of the G2/M checkpoint. In HT-29 cells, the rate of
      transition into mitosis was even higher than in the sham-treated control cells.
      G2/M abrogation was accompanied by an increase of apoptosis only in HPR600 cells.
      CONCLUSIONS: Since PTX was less effective in cells expressing intact p53, the
      application of PTX suggests a promising strategy of pharmacological disruption of
      the G2/M checkpoint control by which preferentially radiation-resistant tumours
      with defective p53 function might be rendered more sensitive to ionizing
      radiation.

PMID- 12194757
TI  - Modification of ionizing radiation clustered damage: estimate of the migration
      distance of holes through DNA via guanyl radicals under physiological conditions.
AB  - PURPOSE: Guanyl radicals are produced in DNA when it is subjected to oxidation or
      ionizing radiation. The sites at which stable products can be identified can be
      located dozens of base pairs away from the initial site of the electron loss.
      This migration will modify the spatial distribution of damage and tends to
      mitigate the clustering of initial damage generally associated with ionizing
      radiation. The migration distance is presumably a function of the lifetime of the
      intermediate guanyl radical, and we wished to quantify the relationship between
      them. MATERIALS AND METHODS: Aqueous solutions containing plasmid DNA and
      thiocyanate ions were treated with gamma-irradiation. These conditions result in
      the very efficient production of guanyl radicals in the plasmid. We quantified
      the formation of stable guanine oxidation products in the plasmid as strand
      breaks by using the E. coli base excision repair endonuclease formamidopyrimidine
      DNA N-glycosylase (FPG). The effect of two additives on the yield of guanine
      oxidation, nitrite ions and the DNA binding ligand doxorubicin (adriamycin), were
      examined. RESULTS: The presence during irradiation of the DNA-binding ligand
      doxorubicin attenuated the yields of stable oxidized guanine products formed. The
      additional presence of nitrite decreased this effect of doxorubicin. CONCLUSION:
      Because doxorubicin binds strongly to DNA, its ability to attenuate guanine
      oxidation can be interpreted in terms of the migration distance of the
      intermediate guanyl radical. Because nitrite repairs these intermediate guanyl
      radicals by electron transfer, its presence during irradiation decreases their
      lifetime. Therefore, we derived an estimate of the migration distance of guanyl
      radicals as a function of their lifetime. The presence in cells of antioxidants
      such as glutathione sets an upper limit to the likely lifetime and, therefore,
      the migration distance of guanyl radicals. It was concluded that the migration of
      guanyl radicals may not decrease the clustering of DNA damage in vivo to a great
      extent.

PMID- 12194758
TI  - Relative biological effectiveness of boron ions on human melanoma cells.
AB  - PURPOSE: To compare the difference in relative biological effectiveness (RBE)
      between (10)B ions and a (60)Co gamma-ray beam for human melanoma cells using in
      vitro cell survival based on a clonogenic assay. MATERIALS AND METHODS: Cells
      were irradiated in vitro under aerobic conditions with (60)Co and (10)B ions with
      different linear energy transfer (LET) (40, 80 and 160 eV nm(-1)). The dose to
      the cells was determined using ferrous sulphate dosimetry and an ionisation
      chamber. The standard linear-quadratic model and the newly proposed repairable
      conditionally repairable damage (RCR) model were used to calculate the RBE.
      RESULTS: The RBE at 10% cell survival for 40, 80 and 160 eV nm(-1) boron ions
      compared with (60)Co were 1.98 (1.83-2.22), 2.85 (2.64-3.11) and 3.37 (3.17
      3.58), respectively, of almost independence of the model used in the calculation.
      CONCLUSIONS: Different cell survival models may generate different RBE,
      especially at low doses and high cell survival levels.

PMID- 12194759
TI  - Report on the Workshop of Biological Applications of X-ray Microbeams.

PMID- 12194761
TI  - Biofilms: microbial life on surfaces.
AB  - Microorganisms attach to surfaces and develop biofilms. Biofilm-associated cells
      can be differentiated from their suspended counterparts by generation of an
      extracellular polymeric substance (EPS) matrix, reduced growth rates, and the up-
      and down- regulation of specific genes. Attachment is a complex process regulated
      by diverse characteristics of the growth medium, substratum, and cell surface. An
      established biofilm structure comprises microbial cells and EPS, has a defined
      architecture, and provides an optimal environment for the exchange of genetic
      material between cells. Cells may also communicate via quorum sensing, which may
      in turn affect biofilm processes such as detachment. Biofilms have great
      importance for public health because of their role in certain infectious diseases
      and importance in a variety of device-related infections. A greater understanding
      of biofilm processes should lead to novel, effective control strategies for
      biofilm control and a resulting improvement in patient management.

PMID- 12194763
TI  - Human metapneumovirus as a cause of community-acquired respiratory illness.
AB  - Human metapneumovirus (HMPV) is a recently identified Paramyxovirus first
      isolated from hospitalized children with acute respiratory tract infections
      (ARTI). We sought evidence of HMPV infection in patients who had visited general
      practitioners, had influenzalike illnesses (ILI), and had negative tests for
      influenza and Human respiratory syncytial virus (HRSV). As part of national
      virologic surveillance, sentinel general practices in England and Wales collected
      samples from patients of all ages with ILI during winter 2000-01. Reverse
      transcriptase-polymerase chain reaction (PCR) for HMPV, influenza A (H1 and H3),
      influenza B, and HRSV (A and B) was used to screen combined nose and throat
      swabs. PCR products from the HMPV-positive samples were sequenced to confirm
      identity and construct phylogenetic trees. Of 711 swabs submitted, 408 (57.3%)
      were negative for influenza and HRSV; HMPV was identified in 9 (2.2%) patients.
      HMPV appears to be associated with community-acquired ARTI. The extent of illness
      and possible complications related to this new human virus need to be clarified.

PMID- 12194762
TI  - A new name (Pneumocystis jiroveci) for Pneumocystis from humans.
AB  - The disease known as Pneumocystis carinii pneumonia (PCP) is a major cause of
      illness and death in persons with impaired immune systems. While the genus
      Pneumocystis has been known to science for nearly a century, understanding of its
      members remained rudimentary until DNA analysis showed its extensive diversity.
      Pneumocystis organisms from different host species have very different DNA
      sequences, indicating multiple species. In recognition of its genetic and
      functional distinctness, the organism that causes human PCP is now named
      Pneumocystis jiroveci Frenkel 1999. Changing the organism's name does not
      preclude the use of the acronym PCP because it can be read "Pneumocystis
      pneumonia." DNA sequence variation exists among samples of P. jiroveci, a feature
      that allows reexamination of the relationships between host and pathogen. Instead
      of lifelong latency, transient colonization may be the rule.

PMID- 12194764
TI  - Molecular epidemiology of measles viruses in the United States, 1997-2001.
AB  - From 1997 to 2001, sequence data from 55 clinical specimens were obtained from
      confirmed measles cases in the United States, representing 21 outbreaks and 34
      sporadic cases. Sequence analysis indicated the presence of 11 of the recognized
      genotypes. The most common genotypes detected were genotype D6, usually
      identified from imported cases from Europe, and genotype D5, associated with
      importations from Japan. A number of viruses belonging to genotype D4 were
      imported from India and Pakistan. Overall, viral genotypes were determined for 13
      chains of transmission with an unknown source of virus, and seven different
      genotypes were identified. Therefore, the diversity of Measles virus genotypes
      observed in the United States from 1997 to 2001 reflected multiple imported
      sources of virus and indicated that no strain of measles is endemic in the United
      States.

PMID- 12194765
TI  - Public health impact of reemergence of rabies, New York.
AB  - This report summarizes the spread of a raccoon rabies epizootic into New York in
      the 1990s, the species of animals affected, and human postexposure treatments
      (PET). A total of 57,008 specimens were submitted to the state laboratory from
      1993 to 1998; 8,858 (16%) animals were confirmed rabid, with raccoons the most
      common species (75%). After exposure to 11,769 animals, 18,238 (45%) persons
      received PET, mostly because of contact with saliva or nervous tissue. We
      analyzed expenditure reports to estimate the cost of rabies prevention
      activities. An estimated $13.9 million was spent in New York State to prevent
      rabies from 1993 to 1998. Traditional prevention methods such as vaccinating
      pets, avoiding wildlife, and verifying an animal's rabies status must be
      continued to reduce costly PET. To reduce rabid animals, exposures, and costs,
      oral vaccination of wildlife should also be considered.

PMID- 12194766
TI  - Impact of the El Nino/Southern Oscillation on visceral leishmaniasis, Brazil.
AB  - We used time-series analysis and linear regression to investigate the
      relationship between the annual Nino-3 index from 1980 to 1998 and the annual
      incidence of visceral leishmaniasis (VL) in the State of Bahia, Brazil, during
      1985-1999. An increase in VL incidence was observed in the post-El Nino years
      1989 (+38.7%) and 1995 (+33.5%). The regression model demonstrates that the
      previous year's mean Nino-3 index and the temporal trend account for
      approximately 50% of the variance in the annual incidence of VL in Bahia. The
      model shows a robust agreement with the real data, as only the influence of El
      Nino on the cycle of VL was analyzed. The results suggest that this relationship
      could be used to predict high-risk years for VL and thus help reduce health
      impact in susceptible regions in Brazil.

PMID- 12194767
TI  - Characterization of flagella produced by clinical strains of Stenotrophomonas
      maltophilia.
AB  - Stenotrophomonas maltophilia is an emerging nosocomial pathogen associated with
      opportunistic infections in patients with cystic fibrosis, cancer, and HIV.
      Adherence of this organism to abiotic surfaces such as medical implants and
      catheters represents a major risk for hospitalized patients. The adhesive surface
      factors involved in adherence of these bacteria are largely unknown, and their
      flagella have not yet been characterized biochemically and antigenically. We
      purified and characterized the flagella produced by S. maltophilia clinical
      strains. The flagella filaments are composed of a 38-kDa subunit, SM(FliC), and
      analysis of its N-terminal amino acid sequence showed considerable sequence
      identity to the flagellins of Serratia marcescens (78.6%), Escherichia coli,
      Proteus mirabilis, Shigella sonnei (71.4%), and Pseudomonas aeruginosa (57.2%).
      Ultrastructural analysis by scanning electron microscopy of bacteria adhering to
      plastic showed flagellalike structures within the bacterial clusters, suggesting
      that flagella are produced as the bacteria spread on the abiotic surface.

PMID- 12194768
TI  - Demographic factors associated with hantavirus infection in bank voles
      (Clethrionomys glareolus).
AB  - The bank vole (Clethrionomys glareolus) is the natural reservoir of Puumala virus
      (PUUV), a species in the genus Hantavirus. PUUV is the etiologic agent of
      nephropathia epidemica, a mild form of hemorrhagic fever with renal syndrome.
      Factors that influence hantavirus transmission within host populations are not
      well understood. We evaluated a number of factors influencing on the association
      of increased PUUV infection in bank voles captured in a region in northern Sweden
      endemic for the virus. Logistic regression showed four factors that together
      correctly predicted 80% of the model outcome: age, body mass index, population
      phase during sampling (increase, peak, or decline/low), and gender. This analysis
      highlights the importance of population demography in the successful circulation
      of hantavirus. The chance of infection was greatest during the peak of the
      population cycle, implying that the likelihood of exposure to hantavirus
      increases with increasing population density.

PMID- 12194769
TI  - Behavioral, physiologic, and habitat influences on the dynamics of Puumala virus
      infection in bank voles (Clethrionomys glareolus).
AB  - Populations of bank voles (Clethrionomys glareolus) were monitored during a 4
      year study in southern Belgium to assess the influence of agonistic behavior,
      reproductive status, mobility, and distribution of the rodents on the dynamics of
      Puumala virus (abbreviation: PUUV; genus: Hantavirus) infection. Concordance was
      high between data from serologic testing and results of viral RNA detection.
      Wounds resulting from biting or scratching were observed mainly in adult rodents.
      Hantavirus infection in adults was associated with wounds in the fall, i.e., at
      the end of the breeding season, but not in spring. In addition, sexually active
      animals were significantly more often wounded and positive for infection.
      Hantavirus infection was associated with higher mobility in juvenile and subadult
      males. Seroconversions observed 6 months apart also occurred more frequently in
      animals that had moved longer distances from their original capture point. During
      nonepidemic years, the distribution of infection was patchy, and positive foci
      were mainly located in dense ground vegetation.

PMID- 12194770
TI  - A case-case comparison of Campylobacter coli and Campylobacter jejuni infection:
      a tool for generating hypotheses.
AB  - Preventing campylobacteriosis depends on a thorough understanding of its
      epidemiology. We used case-case analysis to compare cases of Campylobacter coli
      infection with cases of C. jejuni infection, to generate hypotheses for infection
      from standardized, population-based sentinel surveillance information in England
      and Wales. Persons with C. coli infection were more likely to have drunk bottled
      water than were those with C. jejuni infection and, in general, were more likely
      to have eaten pate. Important differences in exposures were identified for these
      two Campylobacter species. Exposures that are a risk for infection for both
      comparison groups might not be identified or might be underestimated by case-case
      analysis. Similarly, the magnitude or direction of population risk cannot be
      assessed accurately. Nevertheless, our findings suggest that case-control studies
      should be conducted at the species level.

PMID- 12194771
TI  - Spatial analysis of human granulocytic ehrlichiosis near Lyme, Connecticut.
AB  - Geographic information systems combined with methods of spatial analysis provide
      powerful new tools for understanding the epidemiology of diseases and for
      improving disease prevention and control. In this study, the spatial distribution
      of a newly recognized tick-borne disease, human granulocytic ehrlichiosis (HGE),
      was investigated for nonrandom patterns and clusters in an area known to be
      endemic for tick-borne diseases. Analysis of confirmed cases of HGE identified in
      1997-2000 in a 12-town area around Lyme, Connecticut, showed that HGE infections
      are not distributed randomly. Smoothed HGE incidence was higher around the mouth
      of the Connecticut River and lower to the north and west. Cluster analysis
      identified one area of increased HGE risk (relative risk=1.8, p=0.001). This
      study demonstrates the utility of geographic information systems and spatial
      analysis to clarify the epidemiology of HGE.

PMID- 12194772
TI  - Molecular characterization of Campylobacter jejuni clones: a basis for
      epidemiologic investigation.
AB  - A total of 814 isolates of the foodborne pathogen Campylobacter jejuni were
      characterized by multilocus sequence typing (MLST) and analysis of the variation
      of two cell-surface components: the heat-stable (HS) serotyping antigen and the
      flagella protein FlaA short variable region. We identified 379 combinations of
      the MLST loci (sequence types) and 215 combinations of the cell-surface
      components among these isolates, which had been obtained from human disease,
      animals, food, and the environment. Despite this diversity, 748 (92%) of the
      isolates belonged to one of 17 clonal complexes, 6 of which contained many (318,
      63%) of the human disease isolates. Several clonal complexes exhibited
      associations with isolation source or particular cell-surface components;
      however, the latter were poorly predictive of clonal complex. These data
      demonstrate that the clonal complex, as defined by MLST, is an epidemiologically
      relevant unit for both long and short-term investigations of C. jejuni
      epidemiology.

PMID- 12194773
TI  - The 2000 tularemia outbreak: a case-control study of risk factors in disease
      endemic and emergent areas, Sweden.
AB  - A widespread outbreak of tularemia in Sweden in 2000 was investigated in a case
      control study in which 270 reported cases of tularemia were compared with 438
      controls. The outbreak affected parts of Sweden where tularemia had hitherto been
      rare, and these "emergent" areas were compared with the disease-endemic areas.
      Multivariate regression analysis showed mosquito bites to be the main risk
      factor, with an odds ratio (OR) of 8.8. Other risk factors were owning a cat (OR
      2.5) and farm work (OR 3.2). Farming was a risk factor only in the disease
      endemic area. Swollen lymph nodes and wound infections were more common in the
      emergent area, while pneumonia was more common in the disease-endemic area.
      Mosquito bites appear to be important in transmission of tularemia. The
      association between cat ownership and disease merits further investigation.

PMID- 12194774
TI  - First characterization of a cluster of VanA-type glycopeptide-resistant
      Enterococcus faecium, Colombia.
AB  - From August 1998 to October 1999, glycopeptide-resistant enterococci (GRE) were
      isolated from 23 infected patients at a teaching hospital in Medellin, Colombia.
      Identification at the species level and by multiplex polymerase chain reaction
      assay indicated that all isolates were Enterococcus faecium. The isolates were
      highly resistant to ampicillin, ciprofloxacin, gentamicin, penicillin,
      streptomycin, teicoplanin, and vancomycin; they were susceptible only to
      chloramphenicol, linezolid, and nitrofurantoin. Determination of glycopeptide
      genotype indicated the presence of the vanA gene in all isolates. Molecular
      typing by pulsed field gel electrophoresis showed that all isolates were closely
      related. This study is the first molecular characterization of GRE in Colombia.

PMID- 12194775
TI  - Community-acquired methicillin-resistant Staphylococcus aureus in
      institutionalized adults with developmental disabilities.
AB  - Methicillin-resistant Staphylococcus aureus (MRSA) has recently been reported to
      emerge in the community setting. We describe the investigation and control of a
      community-acquired outbreak of MRSA skin infections in a closed community of
      institutionalized adults with developmental disabilities. In a 9-month period in
      1997, 20 (71%) of 28 residents had 73 infectious episodes. Of the cultures, 60%
      and 32% obtained from residents and personnel, respectively, grew S. aureus; 96%
      and 27% were MRSA. All isolates were genetically related by pulsed-field gel
      electrophoresis and belonged to a phage type not previously described in the
      region. No known risk factors for MRSA acquisition were found. However, 58
      antibiotic courses had been administered to 16 residents during the preceding 9
      months. Infection control measures, antibiotic restriction, and appropriate
      therapy resulted in successful termination of this outbreak. Selective antibiotic
      pressure may result in the emergence, persistence, and dissemination of MRSA
      strains, causing prolonged disease.

PMID- 12194776
TI  - Biological warfare at the 1346 siege of Caffa.
AB  - On the basis of a 14th-century account by the Genoese Gabriele de' Mussi, the
      Black Death is widely believed to have reached Europe from the Crimea as the
      result of a biological warfare attack. This is not only of great historical
      interest but also relevant to current efforts to evaluate the threat of military
      or terrorist use of biological weapons. Based on published translations of the
      de' Mussi manuscript, other 14th-century accounts of the Black Death, and
      secondary scholarly literature, I conclude that the claim that biological warfare
      was used at Caffa is plausible and provides the best explanation of the entry of
      plague into the city. This theory is consistent with the technology of the times
      and with contemporary notions of disease causation; however, the entry of plague
      into Europe from the Crimea likely occurred independent of this event.

PMID- 12194777
TI  - Respiratory tract reinfections by the new human Metapneumovirus in an
      immunocompromised child.
AB  - The human Metapneumovirus (HMPV), a new member of the Paramyxoviridae family, has
      been recently associated with respiratory tract infections in young children. We
      report the case of a young, immunocompromised child who had severe lower
      respiratory tract infections during two consecutive winter seasons caused by
      genetically distinct HMPV strains.

PMID- 12194778
TI  - Detection by enzyme-linked immunosorbent assay of antibodies to West Nile virus
      in birds.
AB  - We adapted an indirect immunoglobulin G enzyme-linked immunosorbent assay to
      facilitate studies of West Nile virus (WNV) and evaluated its application to
      taxonomically diverse avian species. Anti-WNV antibodies were detected in 23 bird
      species, including many exotic species, demonstrating its value in studies of WNV
      epizootiology.

PMID- 12194779
TI  - First detection of spotted fever group rickettsiae in Ixodes ricinus from Italy.
AB  - Ixodes ricinus from Italy were examined for the first time to detect whether
      rickettsiae were present. Using molecular methods, we detected three different
      spotted fever group rickettsiae, including Rickettsia helvetica. Our results
      raise the possibility that bacteria other than R. conorii are involved in
      rickettsial diseases in Italy.

PMID- 12194780
TI  - Antibodies to Nipah-like virus in bats (Pteropus lylei), Cambodia.
AB  - Serum specimens from fruit bats were obtained at restaurants in Cambodia. We
      detected antibodies cross-reactive to Nipah virus by enzyme immunoassay in 11
      (11.5%) of 96 Lyle's flying foxes (Pteropus lylei). Our study suggests that
      viruses closely related to Nipah or Hendra viruses are more widespread in
      Southeast Asia than previously documented.

PMID- 12194781
TI  - Cerebral aspergillosis caused by Neosartorya hiratsukae, Brazil.
AB  - We report the first case of infection by Neosartorya hiratsukae, an ascomycete in
      which the conidial state resembles Aspergillus fumigatus. The fungus caused a
      brain infection in a Brazilian woman, who died despite itraconazole treatment.
      Diagnosis was established by direct microscopic examination, computed tomographic
      scan, and magnetic resonance imaging of the brain, and repeated cultures from the
      lesions. The in vitro antifungal susceptibility of the isolate is provided.

PMID- 12194782
TI  - Cyclosporiasis outbreak in Germany associated with the consumption of salad.
AB  - This outbreak is the first foodborne cyclosporiasis outbreak reported from
      central Europe. The illness was reported in 34 persons who attended luncheons at
      a German restaurant. The overall attack rate was 85% (34/40). The only foods
      associated with significant disease risk were two salad side dishes prepared from
      lettuce imported from southern Europe and spiced with fresh green leafy herbs
      (p=0.0025).

PMID- 12194783
TI  - Seroepidemiology of human enterovirus 71, Singapore.
AB  - Human enterovirus 71 has caused outbreaks in many parts of the world, especially
      Southeast Asia, with some fatal cases. The epidemiology of this viral infection
      is not well understood. We conducted a serologic survey in Singapore children,
      and the results indicate that infection occurs largely in preschool settings.

PMID- 12194784
TI  - Lethal leptospiral pulmonary hemorrhage: an emerging disease in Buenos Aires,
      Argentina.

PMID- 12194785
TI  - First documentation of human Crimean-Congo hemorrhagic fever, Kenya.

PMID- 12194786
TI  - Preparing at the local level for events involving weapons of mass destruction.

PMID- 12194787
TI  - [Genetic basis of essential hypertension in Tibetan].
AB  - OBJECTIVE: To explore the role genetic factor plays in the pathogenes is of
      essential hypertension (EH) among Tibetans and to investigate whether
      angiotensinogen (AGT) is involved in the pathogenesis of EH. METHODS: A case
      control association study was conducted among 353 essential hypertensive subjects
      and 317 genealogic structure-matched normotensive controls, all of Tibetan
      nationality. The correlation between polymorphism of M235T and 6A-->G variant in
      AGT gene and EH susceptibility in Tibetans was examined by polymerase chain
      reaction ( PCR) and PCR/RFLP (restriction fragment lengths polymorphism) with
      AspI and BstN I,respectively. RESULTS: (1) The affection rate of EH among the
      first-degree relatives of Tibetan EH proband was 43.3%. The heritability of EH
      was 77.2% +/- 13.3% by Falconer method. (2) The plasma rennin activity and
      angiotensin II (AngII) level among the EH patients were (1.95 +/- 0.11) microgram
      .L(-1).h(-1) and (72.6 +/- 4.6) ng/L, all significantly higher than those in the
      controls [(1. 59 +/- 0.11) microgram .L(-1).h(-1) and (51.7 +/- 4.6) ng/L, all P
      < 0.05].(3) The -6G allele frequency in the promoter of AGT gene was higher in EH
      group than in the control group (0.36 vs 0.27, kappa(2) = 9.35, P < 0.01). There
      was a weak association between -6A -->G variant and the plasma AngII level, and
      there was no significant difference in the genotype distribution and allele
      frequency of M235T variant between the hypertensive and normotensive groups (P >
      0.05). CONCLUSION: Genetic factor plays an important role in the pathogenesis of
      essential hypertension and angiotensinogen gene might be one of the most key
      susceptibility genes for essential hypertension in Tibetan.

PMID- 12194788
TI  - [Association between low-dose oral contraceptive use and stroke in Chinese
      women].
AB  - OBJECTIVE: To investigate the association between low-dose combined oral
      contraceptive (COC) widely distributed in China and the risk of hemorrhagic
      stroke so as to decrease the adverse reaction of COC. METHODS: A prospective
      cohort study was made among 44 408 women who took hormonal contraceptives (HCs)
      and 75 230 women who used in trauterine device (IUD) in 25 townships and toens in
      Rudong County and Taicang City, Jiangsu Province, to compare the incidence of
      stroke among them from 1 July 1997 to 30 June 2000. RESULTS: (1) The incidence of
      hemorrhagic stroke (age-and-county standardized rates) was 34.74 per 100 000 py
      in the HC cohort, 2.72 times higher than that in the IUD cohort (P < 0.01). The
      incidence of hemorrhagic stroke among women less than 45 years of age was
      remarkably higher in HC cohort than in the IUD cohort. The relative risk of
      incidence of hemorrhagic stroke was 2.17 (1.16, 4.06) among the HC users who had
      stopped HC use for more than 10 years, still significantly higher than among the
      IUD users. (2) The relative risk of incidence of hemorrhagic stroke among the
      women who used low-dose COCs during the survey was 3.60 (1.73, 7.53) times higher
      than that among the IUD users. The relative risk of incidence of hemorrhagic
      stroke was 3.09 (1.26, 7.57) among the women who had stopped low-dose COC use for
      less than five years, however, the risk of hemorrhagic stroke remarkably
      decreased after they stopped taking COC for more than 5 years. (3) No obvious
      increase in incidence of infarctional stroke was found among the women who took
      low-dose COC during the survey. (4) Hypertension might be the most important risk
      factor of hemorrhagic stroke among the low-dose COC users. CONCLUSION: There is
      an obvious increase in risk of hemorrhagic stroke among the Chines women who take
      low-dose of China-made COCs for a long time. The efffect of China-made COCs on
      pathogenesis of hemorrhagic stroke lasts sometime after the discontinuation of
      COC use.

PMID- 12194789
TI  - [Relationship between body mass index and major cardiovascular diseases in
      Chinese population].
AB  - OBJECTIVE: To study the relationship between body mass index (BMI) and major
      cardiovascular diseases (CVD) in Chinese population and explore an optimal range
      of BMI among adult Chinese in terms of prevention of CVD. METHODS: Relevant data
      of 881 498 Chinese persons aged 18 and over in the Third National Sampling Survey
      on Hypertension held in 1991 were collected. The distribution of body weight and
      height and the relationship between BMI and prevalence of CVD were analyzed.
      RESULTS: The average BMI was 21.7 kg/m(2) +/- 3.1 kg/m(2), 21.5 kg/m(2) +/- 2.9
      kg/m(2),and 21.8 kg/m(2) +/- 3.3 kg/m(2) for the whole surveyed adults, the males
      and females respectively. The BMI was on the upward trend along with the age,
      reached the peak at the age 45 approximately 54, and then on a downward trend.
      The mean BMI was 22.4 kg/m(2) +/- 3.3 kg/m(2) for the northern population, 21.5
      kg/m(2) +/- 3.0 kg/m(2) for the western population, and 21.1 kg/m(2) +/- 2.9
      kg/m(2) for the southern population with a significantly difference between any
      two groups (all P < 0.01). The higher the mean BMI, the greater the prevalence of
      hypertension, myocardial infarction and stroke. The odds ratios for hypertension,
      myocardial infarction and stroke among those with the BMI >/= 25.0 approximately
      < 28 kg/m(2) were 2.8, 3.1, and 2.6 respectively, and were 4.8, 4.0, and 2.9
      respectively among those with the BMI >/= 28 kg/m(2) (all P < 0.01) in comparison
      with the values among those with the BMI < 25.0 kg/m(2) after adjustment for age,
      and smoking and drinking habits using multivariate Logistic regression model. The
      odds ratio for clustering of >/= 2 kinds of diseases was 2.9 approximately 4.9
      among those with the BMI >/= 25 approximately < 28 kg/m(2) and 3.4 approximately
      8.9 among those with the BMI >/= 28 (P < 0.01 in comparison with that among those
      with the BMI < 25 kg/m(2)). The risks of myocardial infarction and hypertension
      by BMI were greater than the risk of stroke. CONCLUSION: BMI less than 25 kg/m(2)
      is considered as an optimal range among Chinese adults. The BMI values of 25
      kg/m(2) and 28 kg/m(2) can be recommended as thresholds of overweight and obesity
      for Chinese adults aged >/=18 respectively.

PMID- 12194790
TI  - [Prognosis of non-small cell lung cancer patients with microscopic residual
      disease at bronchial stump after lung resection].
AB  - OBJECTIVE: To investigate the prognosis of patients of non-small cell lung cancer
      (NSCLC) receiving lobectomy or pneumonectomy with microscopic residual disease
      (MRD) at the bronchial resection margin postoperatively and analyze the factors
      influencing prognosis. METHODS: The data of 1 218 patients who under went
      lobectomy or pneumonectomy for NSCLC 1965 approximately 1995 were retrospectively
      studied. Staging was done according to the TNM and UICC classifications. The
      factors influencing survival were analysed with Likelihood Ratio method. RESULTS:
      Of the 1 218 patients, 62 suffered form MRD (5.1%) at the bronchial margin
      postoperatively, including 21 MMRD cases and 41 EMRD cases, with a median
      survival time of 44 months and a five-year survival rate of 33.9%. Forty-two
      patients received adjuvant chemotherapy after operation. According to pTNM
      classification,the five-year survival rate was 51.4% for stage I,16.7% for stage
      II,and 6.7% for stage III a respectively, being significantly higher for stage I
      than for stage II and III a (P = 0.001 1). The 5-year survival rate in the MMRD
      group was 57.1%, significantly higher than that in the EMRD group (22.0%, P =
      0.0078). The five-year survival rate in the MRD patients who received adjuvant
      therapy postoperatively was 42.86%, significantly higher than that in those
      without postoperative therapy (15%, P = 0.002). CONCLUSION: The factors
      influencing the prognosis of MRD patients receiving lobectomy or pneumonectomy
      for NSCLC include the pathological stage and the type of infiltration of MRD.
      Chemotherapy after operation improves the prognosis in those patients.

PMID- 12194791
TI  - [Incidence of senile dementia and depression in elderly population in Xicheng
      District, Beijing, an epidemiologic study].
AB  - OBJECTIVE: To investigate the incidence of senile dementia and depression in the
      elderly and the factors correlative with these disorders. METHODS: All the non
      case subjects investigated in a survey of prevalence of senile dementia and
      depression conducted among the elderly population in Xicheng District, Beijing in
      1997 were followed up in 1999. The investigation procedure, instruments and
      diagnostic criteria were identical with those used in 1997 survey. RESULTS: The
      annual incidence rates of senile dementia was 0.89% in those aged 60 and over.
      The incidence rate of old males and that of the old females were not
      significantly different. The annual incidence rate of senile dementia in groups
      aged 60 approximately 64, 64 approximately 69, 70 approximately 74 75
      approximately 79 80 approximately 84 85 approximately 89, and 90 and over were
      0.15% 0.68 % 0.44% 1.32% 2.41% 5.72% and 5.13% respectively. The incidence rate
      in the elderly over 90 was lower than that in the group aged 85 approximately 89.
      The minimum annual incidence rate of depression in the elderly aged 60 and over
      was 1.28%. The incidence rate of depression was higher in the group with poorer
      health than in the group with better health. The incidence rates of moderate and
      severe dementia were not significantly different from those in 1989. CONCLUSION:
      The incidence rate of senile dementia in the elderly remains rather stable during
      this period of 10 years in Beijing city. The incidence rate of senile dementia is
      closely correlated with age. The incidence rate of depression in the elderly is
      remarkably correlated with health status. Senile dementia and depression may
      coexist in the same person.

PMID- 12194792
TI  - [Association analysis of childhood absence epilepsy by microsatellite DNA].
AB  - OBJECTIVE: To investigate whether or not the gamma-aminobutyric acid  GABA  
      receptor subtype Alpha genes  GABRA5 and GABRB3 are associated with childhood
      absence epilepsy  CAE  . METHODS: Five microsatellite DNA  69CA  85CA  155CA1 
      155CA2 and A55CA1  adjacent to chromosome 15q11-15q13 were used as genetic
      markers. Fluorescence-based semi-automated genotyping technique was used in 90
      CAE patients and 100 normal controls to conduct genotyping. Case-control study
      was used to do association analysis. RESULTS: In Chinese normal population the
      allele frequencies of the five microsatellite DNAs were in good agreement with
      Hardy- Weinberg equilibrium. The polymorphism information content   PIC  of the
      five microsatellite DNA were 0.47  0.82  0.66  0.86, and 0.86 respectively. The
      frequencies of some alleles of the 5 microsatellite DNAs in CAE patients were
      significantly higher than those in normal controls. CONCLUSION: Four of the five
      microsatellite DNAs are good genetic markers. GABA subtype Alpha genes  GABRA5
      and GABRB3 may be associated with the pathogenic mechanism of CAE.

PMID- 12194793
TI  - [Expression of pi glutathione S-transferase in intestinal metaplasia and its
      relationship with Helicobacter pylori infection].
AB  - OBJECTIVE: To study the dynamic change of glutathione S- transferase pi (GST-pi)
      in normal gastric mucosa, gastric mucosa with intestinal metaplasia (IM) and
      gastric cancer and to investigate the relationship between human carcinogen
      detoxification system and the virulence of Helicobacter pylori(H.pylori) in the
      stage of IM. METHODS: Two hundred and nineteen biopsy specimens of gastric
      mucosa, including 30 cases with normal gastric mucosa, 171 cases with IM and 18
      cases with gastric cancer, were examined. The expression of GST-pi was detected
      by S-P immunohistochemical method. High-iron diamine /alcian blue pH2.5/periodic
      acid -Schiff (HID-ABpH 2.5-PAS) method was used to classify IM. H.pylori
      infection was confirmed or excluded by hematoxylin-eosin (HE) staining, of
      H.pylori-DNA PCR and ELISA. The 80 cases with H.pylori infection were treated by
      bismuthate + amoxicillin + metronidazole for three months and then biopsy
      specimens were taken again from the original sites. RESULTS: The GST-pi
      expression rate was 69.6% in gastric mucosa with IM, significantly higher than
      that in gastric cancer (44.4%, P < 0.05) and that in normal gastric mucosa (0%, P
      <0.01). The GST-pi expression rate in IM II, IM III, and IM I decreased in
      sequence (83.3%, 71.1%, and 48.9%). The GST-pi expression rate in IM without
      H.pylori infection was 79.0%, significantly higher than that in IM with HP
      infection (64.2%, P <0.05). The positive rate of GST-pi expression in H.pylori
      eradicated group was 81.9%, significantly higher than that before H.pylori
      eradication (63.8%, P < 0.01). The GST-pi expression rate decreased from normal
      gastric mucous to IM and to gastric cancer, and from IM I -->II-->III too.
      CONCLUSION: IM III with low or no expression of GST-pi is a high-risk condition
      of gastric cancer. The risk of gastric cancer increases when low or no expression
      of GST-pi is combined with H.pylori infection. The carcinogen detoxification role
      of GST-pi and the virulence of H.pylori might interact each other in the stage of
      intestinal metaplasia, the precancerous condition of gastric cancer.

PMID- 12194794
TI  - [Detection and analysis of Helicobacter pylori in oral cavity and stomach from
      chronic gastritis patients].
AB  - OBJECTIVE: To investigate the prevalence of Helicobacter pylori (Hp) in the oral
      cavity of gastritis patients and analyze the genotype similarity of Hp in the
      oral cavity with that in the stomach. METHODS: A total of 384 plaque samples were
      collected from 32 patients with chronic gastritis and chronic periodontitis, one
      supragingival plaque sample and one subgingival plaque sample from one tooth,
      totally 6 teeth having been examined for one patient. Gastric biopsy specimens
      were collected by gastroscopy, four pieces of specimen for one patient, to
      undergo rapid urease test, histopathology, and Warthin-Starry silver staining.
      PCR assay was conducted on each specimen with primers based on the sequences of
      urease C gene and cag A gene specific to Hp to amplify the 294-bp and 400-bp DNA
      fragments. The identity of amplified products was confirmed by restriction
      endonuclease digestion. Two PCR positive products (Hp urease C gene 294 bp
      fragments) from the dental plaque samples and one gastric biopsy specimen from
      one of the four patients in the same family, totalling 12 specimens, were further
      examined by single-strand conformation polymorphism (SSCP). RESULTS: Twenty-seven
      patients (84.4 %) had at least one Hp positive dental plaque sample. In total,
      113 (29.4%) of the 384 tested samples were urease C gene positive and 9 (2.3%)
      were positive for both urease C gene and cag A gene. The Hp positive rate was
      significantly higher in subgingival plaque (71/192, 37%) than in supragingival
      plaque (42/192, 21.9 %) (P < 0.01). The Hp positive rate in dental plaque was
      57.1% (48/84) at the gingiva with the probing depth (PD) >/= 4 mm, significantly
      higher than that at the gingiva with the PD < 4 mm (34.3%, 37/108,P < 0.05). The
      Hp positive rate in the specimens of gastric mucosa was 96.7% (31/32). The Hp in
      the 12 dental plaque specimens and gastric biopsy specimens from the 4 patients
      in the same family had 3 banding patterns all together. One of the patients had
      at least one identical banding pattern in both the plaque specimens and gastric
      biopsy specimens. One specific banding pattern was found in the Hp from the
      dental plaques of all 4 patients. In one patient, the SSCP banding pattern in the
      Hp from dental plaque was inconsistent with that from gastric biopsy specimens.
      CONCLUSION: Hp exists in the oral cavity of gastritis patients. Oral Hp infection
      may be an important source of gastric Hp infection. Familial clustering and oral
      oral transmission of Hp infection exist.

PMID- 12194795
TI  - [Laryngeal reinnervation for unilateral recurrent laryngeal nerve injuries caused
      by thyroid surgery].
AB  - OBJECTIVE: To explore the protocols and effects of laryngeal reinnervation for
      unilateral recurrent laryngeal nerve (RLN) injury caused by thyroid surgery.
      METHODS: Different protocols of laryngeal reinnervation were performed upon 29
      patients with unilateral recurrent laryngeal nerve injury caused by thyroid
      surgery, just coming on to with a course of 2 years, including nerve
      decompression upon 8 cases, end to end anastomosis of recurrent laryngeal nerve
      upon 6 cases, and anastomosis of main branch of ansa cervicalis to recurrent
      laryngeal nerve upon 15 cases. All were been subjected to preoperative and
      postoperative voice recording, acoustic analysis, videolaryngoscopy, stroboscopy
      and electromyography. RESULTS: Nerve decompression had restored the normal
      functional adductory and abductory motion of the vocal cord in 5 patients with a
      course of less than four months. Although functional motion of vocal cord had not
      been recovered in three patients who received nerve decompression, 2 being with a
      course of longer than 4 months and one with a course of less than 4 months, and
      in all cases who received ansa cervicalis anastomosis and end to end anastomosis
      of recurrent laryngeal nerve, these procedures resulted in medialization of vocal
      cords except in two cases, one receiving ansa cervicalis anastomosis, and the
      other receiving end to end anastomosis of RLN. Acoustic parameters (Jitter,
      Shimmer, NNE) measured 6 months after operation of any kind all returned to
      normal, however, without significant difference among different groups (P >
      0.05). The amplitude of evoked potential of reinnervated laryngeal muscles was
      significantly greater in the group of nerve decompression than in the group of
      end to end anastomosis of RLN and group of ansa cervicalis anastomosis (both P <
      0.05). However, the amplitude of evoked potential of reinnervated laryngeal
      muscles between the latter two groups was not significantly different (P > 0.05).
      Except in one case in the end to end anastomosis of RLN group and one case in the
      ansa cervicalis anastomosis group, the mass and tension of the reinnervated vocal
      cord became much the same as the contralateral normal vocal cord and symmetric
      vibration of the vocal cords and physiological phonation were recovered in all
      cases. CONCLUSION: (1) Nerve decompression is the best procedure in laryngeal
      reinnervation. (2) Main branch of ansa cervicalis anastomosis and end to end
      anastomosis of RLN effectively restore the laryngeal vocalization. (3) Selection
      of the laryngeal reinnervation protocols should depend on the course, severity
      and type of nerve injury.

PMID- 12194796
TI  - [Polymorphisms of ACE-1 and MTHFR genes and genetic susceptibility of ischemic
      stroke].
AB  - OBJECTIVE: To study the relationships between polymorphisms of angiotensin
      converting enzyme 1 (ACE-1) gene and N(5),N(10) -methylene-tetra-hydrofolic acid
      reductase (MTHFR) gene and ischemic stroke (IS). METHODS: The polymorphisms of
      ACE-1 and MTHFR genes in the peripheral white blood cells of 143 patients with IS
      and 154 controls were analyzed using PCR- RFLP. RESULTS: The frequencies of II,
      ID, and DD genotypes of ACE-1 gene were 37.1%, 48.3%, and 14.7% respectively in
      IS patients,and were 44.2%, 37.7%, and 18.2% respectively in the controls. The
      relative risk of stroke in IS group was 1.2 times that in the control group. The
      frequencies of TT, CT, and CC genotypes of MTHFR gene were 14.0%; 45.5%, and
      40.5% respectively in the IS group, and 5.2%, 31.8%, and 63.0% respectively in
      the control group. The frequency of TT genotype was 5.2% in the control group and
      1.4% in the IS group (P < 0.05). The frequency of T allele was 21.10% in the
      control group and 36.65% in the IS group (P < 0.01). The individuals with TT + ID
      or CT + ID were more susceptible to IS. The individuals with TT + ID were 4.3
      times susceptible to IS than the controls, and the individuals with CT + ID were
      1.63 times susceptible to IS than the controls. However, the individuals with CC
      + ID were less susceptable to IS in comparison to the controls (P = 0.003).
      CONCLUSION: TT and CT genotypes of MTHFR gene may be the risk factors of IS.
      There is a co-effective action between polymorphisms of ACE-1 gene and those of
      MTHFR gene in the pathogenesis of IS. CC genotype may have a protective effect
      against IS.

PMID- 12194797
TI  - [Inhibition of activation of nuclear factor-KappaBeta enhances apoptosis induced
      by chemotherapeutic drugs in P388 cell line].
AB  - OBJECTIVE: To explore the effects of glucocorticoid on apoptosis of mouse acute
      lymphocytic leukemia P388 cells and activation of nuclear factor-Kappa-gene
      binding (NF-KappaBeta) in P388 cells induced by chemotherapeutic drugs. METHODS:
      Mouse acute lymphcytic leukemia P388 cells were cultured. with 1.0 micro mol/L
      thasone (DXM) hours. Then Cytosine arabinoside  Ara-C), cyclophosphamide  Cy  ,
      and etoposide  VP16  , of different concentrations were added into the cultures.
      Twelve hours later, the apoptosis induced by these drugs in P388 cells was
      analysed by TdT-mediated kappa-dUTP nick and end labeling (Tunel) and DNA
      electrophoresis. P388 cells in the exponential growth stage (1 x 10(6)/ml) were
      cultured with DXM (1.0 micro mol/L) for 2 hours. Then Ara-C, Cy, DXM, and VP16
      were added into the culture. Three hours later electrophoretic mobility shift
      assay (EMSA) was conducted to determine the DNA  binding activation of NF
      KappaBeta. RESULTS: The highest apoptosis rates of P388 cells induced by Ara-C,
      Cy, and VP-16, were 48.3% +/- 2.6%, 21.4% +/- 6.8%, and 38.1% +/- 3.8%,
      respectively. The apoptosis rate of P388 cells induced by Ara-C + DXM was 69.6%
      +/- 7.7%, 44% higher than that induced by only Ara-C (48.3% +/- 2.6%); the
      apoptosis rate of P388 cells induced by Cy + DXM was 35.6% +/- 6.8%, 89% higher
      than that induced by only Cy (21.4% +/- 6.8%); and the apoptosis rate of P388
      cells induced by VP-16 + DXM was 71.9% +/- 9.9%, 66% higher than that induced by
      only VP-16 (38.1% +/- 3.8%) (all P < 0.01). Ara-C, Cy, and VP-16 significantly
      increased the activation of NF-KappaBeta in P388 cells. Pre-processing of 1.0
      micro mol/L DXM suppressed the activation of NF-KappaBeta in P388 cells induced
      by Ara-C, Cy and VP16 by 90  , 71   and 68   respectively. CONCLUSION:
      Chemotherapeutic drugs (Ara-C, Cy, and VP-16) induce apoptosis and meanwhile
      induce the activation of NF-KappaBeta in P388 cells. Glucocorticoids, such as
      DXM, suppress the activation of NF-KappaBeta in leukemic cells, thus increasing
      the apoptosis induced by chemotherapeutic drugs.

PMID- 12194798
TI  - [Establishment of a new pig model for auxiliary partial orthotopic liver
      transplantation].
AB  - OBJECTIVE: To establish a new pig model for auxiliary partial orthotopic liver
      transplantation (APOLT). METHODS: The liver of the donor was removed from its
      body. The left lobe of the liver was resected in vitro, and the right lobe was
      used as a graft. After the left lateral lobe of the recipient was resected, end
      to-side anastomoses were performed between the suprahepatic inferior venae cavae
      of the donor and between the portal veins of the donor liver and those of
      recipient liver respectively. End-to-end anastomosis was performed between the
      hepatic artery of graft and the splenic artery of host. Outside drainage was
      placed in the donor's common bile duct. RESULTS: Model of APOLT was established
      in 5 pigs with a success rate of 80%. The hemodynamics of the recipient was
      stable during and after operation. CONCLUSION: Significant decrease of congestion
      in portal vein and shortened blocking time were obtained because of the
      application of veno-venous bypass in vitro during complete vascular clamping.
      This new procedure, with such advantages as simple vessel processing, quality
      anastomosis, less postoperative hemorrhage and higher success rate, etc,
      effectively prevents ischemical reperfusion injury of the host liver and deserves
      to be spread.

PMID- 12194799
TI  - [Experimental study on effects of self-made miniature axial flow blood pump as
      left ventricle assistance for postischemic heart].
AB  - OBJECTIVE: To evaluate the effects of self-made miniature axial flow blood pump
      as left ventricle assistance for postischemic heart. METHODS: Sixteen adult
      healthy sheep were divided into two groups of 8 sheep. After acute left heart
      failure was induced by selective ligation of the left anterior descending branch
      of coronary artery for 1.5 hours and ligation of the left circumflex branch for
      half an hour, one hour of reperfusion with assistance by self-made blood pump was
      offered in experimental group and no mechanical assistance was given to the
      control group. The sheep were killed after the experiment and their hearts were
      taken to be observed. During the experiment, the changes in hemodynamic and
      hemologic indices were compared between the two groups to assess the effects of
      left heart assistance on hemodynamics and blood by self-made blood pump. RESULTS:
      After 1 hour of assistance by self-made blood pump, experimental group, in
      comparison with the control group, showed a significant (P < 0.05) increase in
      total cardial output (3.11 +/- 0.3 vs 2.37 +/- 0.3 L/min), mean aortic pressure
      (73 +/- 5.4 vs 66 +/- 3.1 mm Hg), and left ventricular Dp/Dt(max) (1 415 +/- 2
      549 vs 986 +/- 8 mm Hg/sec); and a significant decrease in left ventricular end
      diastolic pressure (11.8 +/- 2.1 vs 13.5 +/- 1.4 mm Hg) and left atrial pressure
      (14.1 +/- 1.6 vs 16.0 +/- 1.6 mm Hg) (all P < 0.05). There was no significant
      difference in plasma free hemoglobin (12.4 +/- 3.1 vs 13.8 +/- 4.7 mg/dl) and
      fibrinogen (0.32 +/- 0.12 vs 0.42 +/- 0.12 g/dl) between these two groups.
      CONCLUSION: 1, Animal model for acute left heart failure can be achieved by
      selective ligation of coronary arteries and satisfactorily used in left
      ventricular assist device assessment. 2. Self-made blood pump can be used in
      assistance for failure heart without serious event.

PMID- 12194800
TI  - [Therapeutic effects of pulmonary surfactant on smoking-induced lung injury in
      rats, an experimental study].
AB  - OBJECTIVE: To investigate the therapeutic effects of pulmonary surfactant (PS) on
      smoking-induced lung injury in rats. METHODS: Thirty male Wistar rats were
      randomly divided into four groups: normal control group (n = 8, killed by the end
      of the 7th week), 3-week smoking group (n = 8, in haling mainstream smoke of
      cigarette for 3 weeks and killed by the end of the 3rd week), 7-week smoking
      group (n = 8, in haling mainstream smoke of cigarette for 7 weeks and killed by
      the end of the 7th week), and PS treatment group (n = 6, inhaling mainstream
      smoke of cigarette for 7 weeks and given PS 25 mg/kg via trachea per week for 4
      weeks since the end of the 3rd week of smoking, totally 5 times, and then killed
      by the end of the 7th week). The histological changes of respiratory bronchioles
      were observed by light microscopy and transmission electron microscopy. The
      airway resistance in expiratory phase was tested by pulmonary function test
      apparatus. The expression of Clara cell 16KD protein (CC16) mRNA and SP-C mRNA in
      lung tissue was determined by RT-PCR and the expression of CC16 protein in
      bronchiole epithelial cells was determined by immunohistochemistry. RESULTS: The
      proportion of Clara cell to the respiratory bronchiole epithelial cells was 62%
      in the normal controls, 40% in the 3-week smoking group, 33% in the 7-week
      smoking group, and 56% in the PS treatment group (significantly lower in
      comparison with that in the 7-week group, P < 0.05). Degeneration of Clara cells,
      hyperplasis of type II pneumocytes and increase of area of smooth muscle in
      bronchioles were observed in the three smoking groups, however, such changes were
      the most distinct in the 7-week smoking group and the less distinct in the PS
      treatment group (P < 0.05). In comparison with those in the normal control group,
      the expression of CC16 mRNA, SP-C mRNA and CC16 protein were lower in the three
      smoking groups. However, the expressions of CC16 mRNA and the expression of SP-C
      mRNA in the PS treatment group were significantly higher than those in the 7-week
      smoking group (11.8 +/- 5.1 vs 3.0 +/- 0.9, and 8.5 +/- 3.4 vs 2.5 +/- 0.9, both
      P < 0.05). The mean area of smooth muscle in bronchioles with the diameter less
      than 200 micro m was significantly larger than that in the control group,
      however, the mean area in the PS treatment group was significantly less than that
      in the 7-week smoking group (P < 0.05). The airway resistance in the control
      group (1.62 +/- 0.08 cmH(2)O. L(-1). s(-1)) was lower than those in the 3 smoking
      groups, however, the airway resistance in the PS treatment group was
      significantly lower than that in the 7-week group (1.70 +/- 0.07 cmH(2)O. L(-1).
      s(-1) vs 2.98 +/- 0.65 cmH(2)O. L(-1). s(-1), P < 0.05). CONCLUSION: PS is
      effective in alleviating smoking-induced lung injury in rats. One of the
      mechanisms might be attenuation of the damage in Clara cells and type II
      pneumocytes due to cigarette smoking.

PMID- 12194801
TI  - Malignant gonadal mesothelioma.
AB  - Malignant mesothelioma of the gonads is a rare and highly lethal disease. Most of
      these tumors arise from the tunica vaginalis, which is a continuation of the
      mesothelium similar to the pleura and the peritoneum. However, intratesticular
      and ovarian mesotheliomas have also been described. Occasionally, patients with
      localized disease at the time of detection have been known to survive for more
      than 10 years; however, the majority will not live beyond 5 years, with median
      survival being approximately 23 months. The principle reasons for this are
      difficulty in making a preoperative diagnosis and advanced stage at the time of
      treatment. Surgery forms the mainstay of management for all stages of the tumor.
      Adjuvant therapy in the form of chemotherapy, immunotherapy, or radiotherapy has
      negligible benefit. It is essential to diagnose this rare entity at the early
      stages to allow complete surgical extirpation. For the management of localized
      disease, we suggest the following protocol: initial staging of suspected cases
      with computed tomographic scan of the abdomen and pelvis; radical inguinal
      orchiectomy or hemiscrotectomy; retroperitoneal lymph node dissection in cases
      with positive nodes on scan or biopsy; and inguinal node dissection in cases
      requiring hemiscrotectomy. For advanced or recurrent disease, we suggest local
      radical resection with chemotherapy, including high-dose cisplatin and
      doxorubicin for two cycles of 5 days each; add local radiotherapy for
      uncontrolled locally advanced disease.

PMID- 12194802
TI  - Primary pericardial mesothelioma.
AB  - Pericardial mesothelioma is a rare cancer for which treatment options are
      limited. Operative intervention in pericardial mesothelioma is primarily for
      effusion control, for cytoreduction before multimodal therapy, or to deliver and
      monitor innovative intrapericardial therapies. Misdiagnosis is common. Early
      detection of the disease is the only hope for survival. Echocardiography,
      pathologic examination of pericardial fluid and pericardial biopsy, Gallium-67
      scintigraph, Ber-EP4 antibody, and immunohistochemical procedures can be used.
      Magnetic resonance imaging is emerging as the best modality for demonstrating the
      nature and extent of the constrictive process, and the infiltration to the
      cardiac wall and great vessels. Failure of surgical techniques is usually
      associated with mesothelioma with entrapped heart, a large solid tumor mass, and
      a long history of pericardial effusion. If the tumor is localized, resection is
      the only hope for this rare, but lethal, entity. No single treatment modality is
      efficient by itself. The exact role of intracavitary chemotherapy or irradiation
      remains to be defined. Preliminary clinical application of photodynamic therapy
      and attempts at inhibiting the effects of growth factors, such as vascular
      endothelial growth factor and platelet-derived growth factor, and vaccine
      treatments are being explored. Adenoviral molecular chemotherapy recently
      completed phase I testing. Clinical trials for pleural mesothelioma remain
      important as clinicians seek to improve the outcome for patients with pericardial
      mesothelioma. Early diagnosis and multidisciplinary patient care is essential for
      improved surgical outcome. In the future, combined therapeutic strategies
      involving radical surgery, radiotherapy, adjuvant chemotherapy, and
      immunomodulation may have a role in the treatment of pericardial mesotheliomas.

PMID- 12194803
TI  - Peritoneal mesothelioma.
AB  - Peritoneal mesothelioma is usually a rapidly fatal primary peritoneal surface
      malignancy with a median survival time of less than 1 year, mainly because of
      lack of effective treatment. The incidence is approximately one per 1,000,000;
      approximately one fifth to one third of all mesotheliomas are peritoneal. Because
      of its unusual nature, the disease has not been clearly defined in terms of its
      natural history, diagnosis, or management. Treatment options with intravenous
      chemotherapy are far from satisfactory. However, because malignant peritoneal
      mesothelioma usually remains confined to the peritoneal cavity for most of its
      natural history, regional chemotherapy is an attractive option. From a theoretic
      perspective, the treatments are most likely to succeed in selected patients with
      small-volume residual disease after cytoreductive surgery. Advantages of
      intraperitoneal chemotherapy include greatly enhanced drug concentrations in the
      peritoneal cavity and decreased systemic toxicity. In designing an
      intraperitoneal treatment strategy for the management of peritoneal mesothelioma,
      the limited number of active cytotoxic drugs and the timing of drug delivery pose
      problems. Prognosis as determined by clinical presentation, the completeness of
      cytoreduction, and gender (female patients survive longer than male patients)
      appears to be improved by the use of intraperitoneal chemotherapy. Over the past
      decade, the management of these patients has evolved similarly to ovarian cancer
      treatment and now involves cytoreductive surgery, heated intraoperative
      intraperitoneal chemotherapy with cisplatin and doxorubicin, and early
      postoperative intraperitoneal paclitaxel. These perioperative treatments are
      followed by adjuvant intraperitoneal paclitaxel and second-look cytoreduction.
      Prolonged disease-free survival and reduced adverse symptoms with the current
      management strategy are documented by a high complete response rate as assessed
      by a negative second look. This multimodality treatment approach with debulking
      surgery and intraperitoneal chemotherapy has resulted in a median survival of 50
      to 60 months. Peritoneal mesothelioma is an orphan disease that is treatable,
      with expectations for "potential" cure in a small number of patients diagnosed
      and treated early with definitive local/regional treatments. A prolonged high
      quality of life is possible in the majority of patients.

PMID- 12194804
TI  - Urinary diversion after radical cystectomy.
AB  - At most centers with experience in urinary diversion, an orthotopic urinary
      reservoir is the diversion of choice after radical cystectomy for bladder cancer.
      The paradigm has shifted in the past 10 years from actively looking for reasons
      to do an orthotopic diversion to carefully considering why a patient cannot
      undergo reconstruction to their native urethra. In our institution, any patient
      who is to undergo a radical cystectomy for bladder cancer is a potential
      candidate for orthotopic diversion provided they do not have chronic renal
      insufficiency. In addition, they must have a negative urethral margin on frozen
      section at the time of cystectomy, and have the mental and physical capacity to
      understand what is required to manage the reservoir after surgery. Proper patient
      selection is the key to success. Notably, chronologic age is not an absolute
      contraindication to orthotopic diversion. Instead, careful consideration of the
      patient's comorbid conditions should guide eligibility. In addition, locally
      advanced disease is not a contraindication to an orthotopic diversion. To have
      the flexibility to manage whatever situation presents itself intraoperatively,
      the surgeon performing a urinary diversion after radical cystectomy must be
      facile with several diversion techniques. At the very least, the surgeon must be
      comfortable with one type of each major form of urinary diversion, a conduit
      (incontinent) diversion, a continent cutaneous diversion, and an orthotopic
      diversion. As a result, radical cystectomy and urinary diversion should be
      performed at centers with significant experience in all three types of
      diversions.

PMID- 12194805
TI  - Superficial bladder cancer.
AB  - Superficial bladder cancer can be resected with minimal morbidity, but the
      patients are at high risk for tumor recurrence. Tumors can be divided into low-,
      intermediate-, and high-risk categories based on tumor grade, stage, and pattern
      of recurrence. Low-risk tumors are best treated with a single instillation of
      chemotherapy such as thiotepa, doxorubicin, or mitomycin. Intermediate-risk
      tumors can be treated with chemotherapy, but, similar to high-risk tumors, will
      often require immunotherapy. High-risk tumors are best treated with intravesical
      bacille Calmette-Guerin (BCG) using a 3-week maintenance schedule. Side effects
      of BCG immunotherapy can be reduced by logarithmic reductions in the dosage of
      BCG. Patients who fail BCG may be rescued with BCG plus interferon-alfa or
      radical cystectomy.

PMID- 12194807
TI  - Localized prostate cancer: brachytherapy.
AB  - Brachytherapy is a treatment for localized prostate cancer that has become
      popular with physicians and patients. The use and convenience of transrectal
      ultrasound and transperineal placement of the sources make contemporary forms of
      this procedure more accurate and more patient-friendly than their predecessors.
      In addition, the early detection of cancer by the use of prostate-specific
      antigen (PSA) makes contemporary tumors more amenable to successful treatment by
      such a localized technique. Brachytherapy offers cancer control rates at 5 years,
      as measured by PSA, that seem to be as effective as surgery and external beam
      therapy. Less information is available for 10 years, and none afterward. The
      acute urinary morbidity rate of brachytherapy is higher than for external beam
      therapy, but the late urinary morbidity rate is probably equal. The rectal
      morbidity rate is less. The risk of erectile impotence is uncertain but not as
      low as originally hoped. The use of external radiation in combination with
      brachytherapy may increase 5-year tumor control rates but is substantially more
      expensive and likely carries an increased risk of morbidity. Newer forms of
      brachytherapy such as magnetic resonance-guided and high-dose-rate temporary
      implants have vocal advocates but a shorter track record and fewer published
      prospective studies. Their use remains investigational. Therefore, prostate
      brachytherapy remains a reasonable option for men with early stage disease, but
      there remain unanswered questions regarding long-term efficacy and morbidity.

PMID- 12194806
TI  - Localized and locally advanced bladder cancer.
AB  - Localized and locally advanced bladder cancer represents a heterogeneous spectrum
      of diseases with different biologic and clinical behavior. It varies with respect
      to invasive potential, propensity for metastases, and sensitivity to
      chemotherapy. Although several significant surgical advances have been made over
      the past 20 years in the treatment of muscle-invasive bladder cancer, resulting
      in decreases in perioperative morbidity and mortality and improvement of quality
      of life in patients with continent urinary diversions, the natural history of the
      disease has remained unaltered. Advances in chemotherapy for metastatic disease
      have prompted trials of systemic therapy in patients with early stage, high-risk
      disease administered before or after local therapy consisting of cystectomy or
      radiotherapy. The data available from nonrandomized and randomized trials have
      not definitively established the exact role of neoadjuvant chemotherapy and its
      impact on survival. Even if neoadjuvant chemotherapy does not improve survival,
      preliminary data suggest that bladder preservation may be possible in selected
      patients and that such combined therapy will hopefully lead to better patient
      management. The trials of postoperative chemotherapy provide insufficient
      evidence to support the routine use of adjuvant chemotherapy in clinical practice
      as a result of small sample size, confusing analyses, and the reporting of
      questionable conclusions. New large-scale, multicenter trials are imperative to
      provide convincing results. A better understanding of the microbiology of bladder
      cancer will influence the search for new therapeutic modalities. Molecular
      targeted small-molecule therapy and monoclonal antibodies have begun to dominate
      contemporary studies.

PMID- 12194808
TI  - Hormone-refractory Prostate Cancer.
AB  - For more than five decades, the preferred treatment for advanced prostate cancer
      has been suppression of androgen production by medical or surgical castration.
      However, all patients treated with androgen deprivation eventually develop
      resistant disease as manifested by increasing prostate-specific antigen levels,
      progressive disease on imaging studies, and ultimately worsening symptoms. The
      treatment of patients with hormone-refractory prostate cancer (HRPC), once
      thought to represent a relatively futile endeavor, has changed significantly in
      the past several years with the development of new therapeutics. One of the most
      important new treatment strategies involves secondary hormonal manipulation after
      the failure of primary androgen deprivation; this approach is predicated on the
      recognition that HRPC is a heterogenous disease. Some patients may respond to
      alternative hormonal interventions despite the presence of castrate levels of
      testosterone. Furthermore, the application of chemotherapeutic regimens has
      provided viable treatment options for patients with HRPC.

PMID- 12194809
TI  - Management and Prevention of Stroke Associated with Elevated Homocysteine.
AB  - Observational data from prospective and retrospective studies indicate that
      elevated homocyst(e)ine (Hcy) is associated with preclinical markers of
      cerebrovascular disease and ischemic stroke. Although the exact mechanisms of
      this association are unresolved, data indicate that elevated Hcy promotes
      cerebral, arterial, and venous thrombosis, and may predispose to premature
      atherosclerosis and craniocervical arterial dissection. Plasma Hcy is a sensitive
      marker of low folate, B(12), and B(6) status. Data consistently indicate that
      folic acid supplementation in the form of vitamin tablets is the most effective
      strategy to lower mild-to-moderately elevated Hcy, with maximal benefit occurring
      in individuals with higher pretreatment Hcy or lower pretreatment folate levels.
      B(12) supplementation confers a minor additional benefit, whereas B(6)
      supplementation has not been demonstrated to confer further benefit. Despite
      reports that Hcy-lowering therapy may improve surrogate measures of vascular
      disease, the outcomes of clinical trials for secondary stroke prevention are
      pending. Until this information is available, we concur with the American Stroke
      Association guidelines for stroke prevention. Specifically, we recommend good
      dietary intake of foods rich in folic acid, B(6), and B(12) for primary
      prevention, and supplemental multivitamins (folic acid 400 g to 1 mg daily, B(12)
      400 to 600 g daily, B(6) 2 to 10 mg daily) for individuals with known
      cerebrovascular disease and hyper-Hcy.

PMID- 12194811
TI  - Endovascular Treatment for Vertebrobasilar Insufficiency.
AB  - Endovascular management of supra-aortic atherosclerotic vascular disease is
      becoming relatively common in the innominate, subclavian, and carotid arteries.
      However, revascularization of vertebral artery disease is an infrequently used
      treatment option due to several reasons: 1) stroke etiology and prevention is
      generally considered with respect to carotid disease as posterior circulation
      ischemia is poorly defined; 2) the limited success and excessive morbidity have
      made surgery an unattractive option for vertebral artery revascularization; 3)
      routine screening for posterior circulation disease as an etiology for stroke is
      rarely performed; and 4) endovascular treatment of vertebrobasilar insufficiency
      is not routinely performed in peripheral interventional programs. Randomized data
      comparing medical therapy, endovascular treatment, or surgical treatment do not
      exist. Due to infrequent identification of vertebral artery disease as the
      etiology of posterior circulation symptomatology, randomized comparisons will be
      difficult to obtain. Balloon angioplasty alone, provisional stenting, or primary
      stent placement for the treatment of vertebral artery stenosis is associated with
      low restenosis rates and high success rates. The available literature
      demonstrates angioplasty with stent placement of posterior circulation,
      symptomatic, vertebrobasilar atherosclerotic disease is a safe and effective
      approach that avoids the morbidity associated with major surgery. We believe
      primary stent placement is the treatment of choice for vertebral artery
      revascularization due to the high technical success rate, low incidence of
      morbidity and mortality, and long-term durability.

PMID- 12194810
TI  - Cerebral Vasospasm Following Subarachnoid Hemorrhage.
AB  - Cerebral vasospasm and related ischemic stroke continue to be significant
      complicating factors in the course of many patients with subarachnoid hemorrhage
      from berry aneurysm rupture. The risk of this well-recognized but poorly
      understood complication can be estimated on the basis of patient medical history,
      neurologic examination, and head CT findings. Every patient with possible risk
      needs specialized neurologic intensive care unit care after aneurysm
      obliteration. Surgical and pharmacologic wash-out of subarachnoid blood around
      the basal arteries, proper management of intracranial pressure and fluid status,
      hyponatremia, hypomagnesemia, and fever, as well as use of calcium channel
      blockers, have been considered helpful in patient management prior to and with
      the symptomatic vasospasm development. Transcranial Doppler (TCD) ultrasound is
      important in detecting vasospasm before the patient suffers ischemic neurologic
      deficit or infarct. Elevated TCD velocities often initiate the use of triple-H
      (HHH: hypertension, hemodilution, and hypervolemia) therapy and subsequently
      guide it. Up to the end of the first 3 weeks after subarachnoid hemorrhage and
      aneurysm obliteration, development of any focal neurologic deficit or mental
      deterioration, unless convincingly proven otherwise, is assumed to be from
      cerebral vasospasm. When a hemodynamically significant vasospasm in the arterial
      segments of clinical concern is suggested, emergency cerebral angiography with
      balloon dilatation angioplasty or intra-arterial infusion of vasodilating agents
      may be helpful in relieving ischemic symptoms.

PMID- 12194812
TI  - Prevention of Ischemic Stroke.
AB  - The primary risk factors for stroke are known, and attention to primary care of
      these disorders should reduce the incidence of stroke significantly. Control of
      hypertension, diabetes, and hyperlipidemia have all been shown to reduce the rate
      of stroke. Identification of potential cardioembolic sources of stroke,
      particularly atrial fibrillation, can prevent stroke with appropriate application
      of anticoagulation. Duplex Doppler B-mode sonography can establish the extent of
      carotid artery disease in patients with cervical bruit or risk factors for
      atherosclerosis, and indicate which conditions should be managed medically or
      surgically. Patients with a history suggestive of transient ischemic attacks can
      also be screened noninvasively with duplex sonography to determine if they have a
      critical carotid stenosis and require carotid endarterectomy. New advances in
      platelet antiaggregant therapy with ticlopidine, clopidogrel, and the combination
      of aspirin with dipyridamole have also reduced the rate of stroke to a greater
      degree than standard treatment with aspirin. The incidence of this devastating
      illness could possibly be reduced by 50% with attentive primary care management.
      The cardiologist is often involved in the treatment of patients at risk for
      stroke, and is in an ideal position to provide this care.

PMID- 12194813
TI  - Neuroendovascular Rescue: Interventional Treatment of Acute Ischemic Stroke.
AB  - Stroke continues to be a major health problem for our society. Despite the proven
      effectiveness of intravenous tissue plasminogen activator (t-PA) for the
      treatment of acute ischemic stroke, only a minority of patients qualify for this
      type of therapy. Furthermore, the existing literature has demonstrated that t-PA
      is not as effective in the treatment of occlusion of large cerebral arteries. The
      benefit-to-risk assessment of this subpopulation of stroke patients makes them
      the best candidates for neuroendovascular rescue. This term refers to the intra
      arterial application of techniques designed to promote arterial recanalization,
      and includes intra-arterial thrombolysis and antithrombotic agents, direct
      mechanical disruption, angioplasty, stenting, embolectomy, and vasoactive
      pharmacologic intervention. The timing and choice of these procedures, as well as
      the care of the patient prior to, during, and after the intervention, requires a
      highly focused and expert approach.

PMID- 12194814
TI  - Innovative Strategies in the Management of Acute Stroke.
AB  - Advances in acute stroke therapy are rapidly changing our approach to the
      management of patients with ischemic stroke. Intravenous tissue plasminogen
      activator was the first treatment demonstrated in a randomized controlled trial
      to improve outcome if given within the first 3 hours of stroke onset. Subsequent
      trials failed to extend the time window for intravenous therapy beyond 3 hours.
      Intra- arterial thrombolysis provides an alternative approach, with several
      advantages over intravenous therapy. The major drawback is the additional time
      needed for the interventional procedure, and the equipment and personnel
      requirements. New strategies aimed at reducing the total time from stroke onset
      to recanalization of occluded arteries include a combined intravenous/intra
      arterial delivery of thrombolysis and mechanical devices. For the millions of
      stroke survivors, investigations are now underway into the possibility of
      improvement of function through neuronal transplantation.

PMID- 12194815
TI  - Antithrombotic Secondary Prevention After Stroke.
AB  - In patients with transient ischemic attack (TIA) or ischemic stroke of noncardiac
      origin, antiplatelet drugs are able to decrease the risk of stroke by 11% to 15%,
      and decrease the risk of stroke, myocardial infarction (MI), and vascular death
      by 15% to 22%. Aspirin leads to a moderate but significant reduction of stroke,
      MI, and vascular death in patients with TIA and ischemic stroke. Low doses are as
      effective as high doses, but are better tolerated in terms of gastrointestinal
      side effects. The recommended aspirin dose, therefore, is between 50 and 325 mg.
      Bleeding complications are not dose-dependent, and also occur with the lowest
      doses. The combination of aspirin (25 mg twice daily) with slow-release
      dipyridamole (200 mg twice daily) is superior compared with aspirin alone for
      stroke prevention. Ticlopidine is effective in secondary stroke prevention in
      patients with TIA and stroke. For some end points, it is superior to aspirin. Due
      to its side-effect profile (neutropenia, thrombotic thrombocytopenic purpura ),
      ticlopidine should be given to patients who are intolerant of aspirin.
      Prospective trials have not indicated whether ticlopidine is suggested for
      patients who have recurrent cerebrovascular events while on aspirin. Clopidogrel
      has a better safety profile than ticlopidine. Although not investigated in
      patients with TIA, clopidogrel should also be effective in these patients
      assuming the same pathophysiology than in patients with stroke. Clopidogrel is
      second-line treatment in patients intolerant for aspirin, and first-line
      treatment for patients with stroke and peripheral arterial disease or MI. A
      frequent clinical problem is patients who are already on aspirin because of
      coronary heart disease or a prior cerebral ischemic event, and then suffer a
      first or recurrent TIA or stroke. No single clinical trial has investigated this
      problem. Therefore, recommendations are not evidence-based. Possible strategies
      include the following: continue aspirin, add dipyridamole, add clopidogrel,
      switch to ticlopidine or clopidogrel, or switch to anticoagulation with an
      International Normalized Ratio (INR) of 2.0 to 3.0. The combination of low-dose
      warfarin and aspirin was never studied in the secondary prevention of stroke. In
      patients with a cardiac source of embolism, anticoagulation is recommended with
      an INR of 2.0 to 3.0. At the present time, anticoagulation with an INR between
      3.0 and 4.5 cannot be recommended for patients with noncardiac TIA or stroke.
      Anticoagulation with an INR between 3.0 and 4.5 carries a high bleeding risk.
      Whether anticoagulation with lower INR is safe and effective is not yet known.
      Treatment of vascular risk factors should also be performed in secondary stroke
      prevention.

PMID- 12194816
TI  - Interplay between two epigenetic marks. DNA methylation and histone H3 lysine 9
      methylation.
AB  - BACKGROUND: The heterochromatin of many eukaryotes is marked by both DNA
      methylation and histone H3 lysine 9 (H3-K9) methylation, though the exact
      relationship between these epigenetic modifications is unknown. In Neurospora, H3
      K9 methylation is required for the maintenance of all known DNA methylation. In
      Arabidopsis, H3-K9 methylation directs some of the CpNpG and asymmetric
      methylation. However, it is not known in any organism whether DNA methylation may
      also direct histone H3 methylation. RESULTS: Using chromatin immunoprecipitation
      (ChIP) assays, we show that Arabidopsis heterochromatin is associated with H3-K9
      methylation. This histone methylation is dependent on the KRYPTONITE and DDM1
      genes (SU[VAR]3-9 and SWI2/SNF2 homologs, respectively). We also find that a
      decrease in DNA methylation does not directly cause a loss of H3-K9 methylation.
      Instead, a decrease in H3-K9 methylation is only seen at loci where transcription
      is derepressed. CONCLUSIONS: We conclude that DNA methylation does not control
      the methylation of histone H3-K9. We propose that loss of H3-K9 methylation is
      due to transcriptional reactivation, coupled with deposition of unmethylated
      nucleosomes. These findings are consistent with recent observations of DNA
      replication-independent deposition of histone H3.3 in Drosophila. Our results
      also suggest that, in Arabidopsis, DNA methylation is sufficient for gene
      silencing, but H3-K9 methylation is not.

PMID- 12194818
TI  - Dynamic shape integration in extrastriate cortex.
AB  - BACKGROUND: In anorthoscopic viewing conditions, observers can perceive a moving
      object through a narrow slit even when only portions of its contour are visible
      at any time. We used fMRI to examine the contribution of early and later visual
      cortical areas to dynamic shape integration. Observers' success at integrating
      the shape of the slit-viewed object was manipulated by varying the degree to
      which the stimulus was dynamically distorted. Line drawings of common objects
      were either moderately distorted, strongly distorted, or shown undistorted.
      Phenomenologically, increasing the stimulus distortion made both object shape and
      motion more difficult to perceive. RESULTS: We found that bilateral cortical
      activity in portions of the ventral occipital cortex, corresponding to known
      object areas within the lateral occipital complex (LOC), was inversely correlated
      with the degree of stimulus distortion. We found that activity in left MT+, the
      human cortical area specialized for motion, showed a similar pattern as the
      ventral occipital region. The LOC also showed greater activity to a fully visible
      moving object than to the undistorted slit-viewed object. Area MT+, however,
      showed more equivalent activity to both the slit-viewed and fully visible moving
      objects. CONCLUSIONS: In early retinotopic cortex, the distorted and undistorted
      stimuli elicited the same amount of activity. Higher visual areas, however, were
      correlated with the percept of the coherent object, and this correlation suggests
      that the shape integration is mediated by later visual cortical areas. Motion
      information from the dorsal stream may project to the LOC to produce the shape
      percept.

PMID- 12194817
TI  - Regulation of human separase by securin binding and autocleavage.
AB  - BACKGROUND: Sister chromatid separation is initiated by separase, a protease that
      cleaves cohesin and thereby dissolves sister chromatid cohesion. Separase is
      activated by the degradation of its inhibitor securin and by the removal of
      inhibitory phosphates. In human cells, separase activation also coincides with
      the cleavage of separase, but it is not known if this reaction activates
      separase, which protease cleaves separase, and how separase cleavage is
      regulated. RESULTS: Inhibition of separase expression in human cells by RNA
      interference causes the formation of polyploid cells with large lobed nuclei. In
      mitosis, many of these cells contain abnormal chromosome plates with unseparated
      sister chromatids. Inhibitor binding experiments in vitro reveal that securin
      prevents the access of substrate analogs to the active site of separase. Upon
      securin degradation, the active site of full-length separase becomes accessible,
      allowing rapid autocatalytic cleavage of separase at one of three sites. The
      resulting N- and C-terminal fragments remain associated and can be reinhibited by
      securin. A noncleavable separase mutant retains its ability to cleave cohesin in
      vitro. CONCLUSIONS: Our results suggest that separase is required for sister
      chromatid separation during mitosis in human cells. Our data further indicate
      that securin inhibits separase by blocking the access of substrates to the active
      site of separase. Securin proteolysis allows autocatalytic processing of separase
      into a cleaved form, but separase cleavage is not essential for separase
      activation.

PMID- 12194819
TI  - Chemical genetic blockade of transformation reveals dependence on aberrant
      oncogenic signaling.
AB  - BACKGROUND: Our understanding of protein kinase inhibition in the treatment of
      cancer is clearly limited by the lack of inhibitors that selectively block a
      single kinase implicated in neoplastic transformation. One approach to developing
      specific inhibitors is to engineer in protein kinases silent mutations that allow
      selective inhibition while retaining kinase activity. Because it is implicated in
      a large number of malignancies, EGFR provides an attractive target for such
      selective kinase inhibition. RESULTS: We generated an inhibitor-sensitized allele
      of the transforming receptor tyrosine kinase v-erbB. Transformation of
      immortalized rodent fibroblasts by sensitized versions of v-erbB (v-erbB-as1) was
      blocked by 1-napthyl PP1 (NaPP1), a cell-permeable ATP-competitive inhibitor.
      NaPP1 also reversed morphological transformation by v-erbB-as1. Signaling through
      MAP kinase and PI(3) kinase was initially blocked by inhibitor treatment and then
      recovered to levels comparable to those in nontransformed cells. Surprisingly,
      NaPP1-treated v-erbB-as1 cells failed to re-enter the cell cycle, showed
      decreased levels of D- and A-type cyclins, and showed increased levels of p27. To
      extend this result, we showed that NaPP1 treatment of v-Src-as1 cells also led to
      cell cycle arrest. Arrested cells could be rescued with a conditional allele of
      Raf or by transduction of a constitutive allele of cyclin D1. CONCLUSIONS: These
      data suggest that mammalian cells can become dependent on aberrant oncogenic
      signaling; this dependency renders them incapable of returning to a normal,
      proliferative phenotype.

PMID- 12194820
TI  - Phylogenetic analysis of the Wnt gene family. Insights from lophotrochozoan
      members.
AB  - The Wnt gene family encodes secreted signaling molecules that control cell fate
      specification, proliferation, polarity, and movements during animal development.
      We investigate here the evolutionary history of this large multigenic family. Wnt
      genes have been almost exclusively isolated from two of the three main
      subdivisions of bilaterian animals, the deuterostomes (which include chordates
      and echinoderms) and the ecdysozoans (e.g., arthropods and nematodes). However,
      orthology relationships between deuterostome and ecdysozoan Wnt genes, and, more
      generally, the phylogeny of the Wnt family, are not yet clear. We report here the
      isolation of several Wnt genes from two species, the annelid Platynereis
      dumerilii and the mollusc Patella vulgata, which both belong to the third large
      bilaterian clade, the lophotrochozoans (which constitute, together with
      ecdysozoans, the protostomes). Multiple phylogenetic analyses of these sequences
      with a large set of other Wnt gene sequences, in particular, the complete set of
      Wnt genes of human, nematode, and fly, allow us to subdivide the Wnt family into
      12 subfamilies. At least nine of them were already present in the last common
      ancestor of all bilaterian animals, and this further highlights the genetic
      complexity of this ancestor. The orthology relationships we present here open new
      perspectives for future developmental comparisons.

PMID- 12194821
TI  - Neurotrophin-4: a survival factor for adult sensory neurons.
AB  - The nerve growth factor (NGF) family of neurotrophins provides a substantial part
      of the normal trophic support for sensory neurons during development. Although
      these neurotrophins, which include Brain-Derived Neurotrophic Factor (BDNF),
      Neurotrophin-3 (NT-3), and Neurotrophin-4 (NT-4), continue to be expressed into
      adulthood, there is little evidence that they are survival factors for adult
      neurons. Here we have examined the age-dependent neurotrophic requirements of a
      specialized type of mechanoreceptive neuron, called a D-hair receptor, in the
      dorsal root ganglion (DRG). Studies using knockout mice have demonstrated that
      the survival of D-hair receptors is dependent upon both NT-3 and NT-4. Here, we
      show that the time period when D-hair receptors require these two neurotrophins
      is different. Survival of D-hair receptors depends on NT-3 early in postnatal
      development and NT-4 later in the mature animal. The age-dependent loss of D-hair
      neurons in older NT-4 knockout mice was accompanied by a large reduction (78%) in
      neurons positive for the NT-4 receptor (trkB) together with neuronal apoptosis in
      the DRG. This is the first evidence that sensory neurons have a physiological
      requirement for a single neurotrophin for their continued survival in the adult.

PMID- 12194822
TI  - Analysis of a zebrafish VEGF receptor mutant reveals specific disruption of
      angiogenesis.
AB  - Blood vessels form either by the assembly and differentiation of mesodermal
      precursor cells (vasculogenesis) or by sprouting from preexisting vessels
      (angiogenesis). Endothelial-specific receptor tyrosine kinases and their ligands
      are known to be essential for these processes. Targeted disruption of vascular
      endothelial growth factor (VEGF) or its receptor kdr (flk1, VEGFR2) in mouse
      embryos results in a severe reduction of all blood vessels, while the complete
      loss of flt1 (VEGFR1) leads to an increased number of hemangioblasts and a
      disorganized vasculature. In a large-scale forward genetic screen, we identified
      two allelic zebrafish mutants in which the sprouting of blood vessels is
      specifically disrupted without affecting the assembly and differentiation of
      angioblasts. Molecular cloning revealed nonsense mutations in flk1. Analysis of
      mRNA expression in flk1 mutant embryos showed that flk1 expression was severely
      downregulated, while the expression of other genes (scl, gata1, and fli1)
      involved in vasculogenesis or hematopoiesis was unchanged. Overexpression of
      vegf(121+165) led to the formation of additional vessels only in sibling larvae,
      not in flk1 mutants. We demonstrate that flk1 is not required for proper
      vasculogenesis and hematopoiesis in zebrafish embryos. However, the disruption of
      flk1 impairs the formation or function of vessels generated by sprouting
      angiogenesis.

PMID- 12194823
TI  - Rho-kinase and myosin-II control phagocytic cup formation during CR, but not
      FcgammaR, phagocytosis.
AB  - Phagocytosis through Fcgamma receptor (FcgammaR) or complement receptor 3 (CR)
      requires Arp2/3 complex-mediated actin polymerization, although each receptor
      uses a distinct signaling pathway. Rac and Cdc42 are required for actin and
      Arp2/3 complex recruitment during FcgammaR phagocytosis, while Rho controls actin
      assembly at CR phagosomes. To better understand the role of Rho in CR
      phagocytosis, we tested the idea that a known target of Rho, Rho-kinase (ROK),
      might control phagocytic cup formation and/or engulfment of particles. Inhibitors
      of ROK (dominant-negative ROK and Y-27632) and of the downstream target of ROK,
      myosin-II (ML7, BDM, and dominant-negative myosin-II), were used to test this
      idea. We found that inhibition of the Rho --> ROK --> myosin-II pathway caused a
      decreased accumulation of Arp2/3 complex and F-actin around bound particles,
      which led to a reduction in CR-mediated phagocytic engulfment. FcgammaR-mediated
      phagocytosis, in contrast, was independent of Rho or ROK activity and was only
      dependent on myosin-II for particle internalization, not for actin cup formation.
      While myosins have been previously implicated in FcgammaR phagocytosis, to our
      knowledge, this is the first demonstration of a role for myosin-II in CR
      phagocytosis.

PMID- 12194824
TI  - Activation of AMP-activated protein kinase leads to the phosphorylation of
      elongation factor 2 and an inhibition of protein synthesis.
AB  - Protein synthesis, in particular peptide-chain elongation, consumes cellular
      energy. Anoxia activates AMP-activated protein kinase (AMPK, see ), resulting in
      the inhibition of biosynthetic pathways to conserve ATP. In anoxic rat
      hepatocytes or in hepatocytes treated with 5-aminoimidazole-4-carboxamide (AICA)
      riboside, AMPK was activated and protein synthesis was inhibited. The inhibition
      of protein synthesis could not be explained by changes in the phosphorylation
      states of initiation factor 4E binding protein-1 (4E-BP1) or eukaryotic
      initiation factor 2alpha (eIF2alpha). However, the phosphorylation state of
      eukaryotic elongation factor 2 (eEF2) was increased in anoxic and AICA riboside
      treated hepatocytes and in AICA riboside-treated CHO-K1 cells, and eEF2
      phosphorylation is known to inhibit its activity. Incubation of CHO-K1 cells with
      increasing concentrations of 2-deoxyglucose suggested that the mammalian target
      of the rapamycin (mTOR) signaling pathway did not play a major role in
      controlling the level of eEF2 phosphorylation in response to mild ATP depletion.
      In HEK293 cells, transfection of a dominant-negative AMPK construct abolished the
      oligomycin-induced inhibition of protein synthesis and eEF2 phosphorylation.
      Lastly, eEF2 kinase, the kinase that phosphorylates eEF2, was activated in anoxic
      or AICA riboside-treated hepatocytes. Therefore, the activation of eEF2 kinase by
      AMPK, resulting in the phosphorylation and inactivation of eEF2, provides a novel
      mechanism for the inhibition of protein synthesis.

PMID- 12194825
TI  - RIP4 is an ankyrin repeat-containing kinase essential for keratinocyte
      differentiation.
AB  - The epidermis is a stratified, continually renewing epithelium dependent on a
      balance among cell proliferation, differentiation, and death for homeostasis. In
      normal epidermis, a mitotically active basal layer gives rise to terminally
      differentiating keratinocytes that migrate outward and are ultimately sloughed
      from the skin surface as enucleated squames. Although many proteins are known to
      function in maintaining epidermal homeostasis, the molecular coordination of
      these events is poorly understood. RIP4 is a novel RIP (receptor-interacting
      protein) family kinase with ankyrin repeats cloned from a keratinocyte cDNA
      library. RIP4 deficiency in mice results in perinatal lethality associated with
      abnormal epidermal differentiation. The phenotype of RIP4(-/-) mice in part
      resembles that of mice lacking IKKalpha, a component of a complex that regulates
      NF-kappaB. Despite the similar keratinocyte defects in RIP4- and IKKalpha
      deficient mice, these kinases function in distinct pathways. RIP4 functions cell
      autonomously within the keratinocyte lineage. Unlike IKKalpha, RIP4-deficient
      skin fails to fully differentiate when grafted onto a normal host. Instead,
      abnormal hair follicle development and epidermal dysplasia, indicative of
      progression into a more pathologic state, are observed. Thus, RIP4 is a critical
      component of a novel pathway that controls keratinocyte differentiation.

PMID- 12194826
TI  - Enhanced tactile performance at the destination of an upcoming saccade.
AB  - Previous work has demonstrated that upcoming saccades influence visual and
      auditory performance even for stimuli presented before the saccade is executed.
      These studies suggest a close relationship between saccade generation and
      visual/auditory attention. Furthermore, they provide support for Rizzolatti et
      al.'s premotor model of attention, which suggests that the same circuits involved
      in motor programming are also responsible for shifts in covert orienting
      (shifting attention without moving the eyes or changing posture). In a series of
      experiments, we demonstrate that saccade programming also affects tactile
      perception. Participants made speeded saccades to the left and right side as well
      as tactile discriminations of up versus down. The first experiment demonstrates
      that participants were reliably faster at responding to tactile stimuli near the
      location of upcoming saccades. In our second experiment, we had the subjects
      cross their hands and demonstrated that the effect occurs in visual space (rather
      than the early representations of touch). In our third experiment, the tactile
      events usually occurred on the opposite side of upcoming eye movement. We found
      that the benefit at the saccade target location vanished, suggesting that this
      shift is not obligatory but that it may be vetoed on the basis of expectation.

PMID- 12194828
TI  - Targeting of RCC1 to chromosomes is required for proper mitotic spindle assembly
      in human cells.
AB  - Ran GTPase is involved in several aspects of nuclear structure and function,
      including nucleocytoplasmic transport and nuclear envelope formation. Experiments
      using Xenopus egg extracts have shown that generation of Ran-GTP by the guanine
      nucleotide exchange factor RCC1 also plays roles in mitotic spindle assembly.
      Here, we have examined the localization and function of RCC1 in mitotic human
      cells. We show that RCC1, either the endogenous protein or that expressed as a
      fusion with green fluorescent protein (GFP), is localized predominantly to
      chromosomes in mitotic cells. This localization requires an N-terminal lysine
      rich region that also contains a nuclear localization signal and is enhanced by
      interaction with Ran. Either mislocalization of GFP-RCC1 by removal of the N
      terminal region or the expression of dominant Ran mutants that perturb the
      GTP/GDP cycle causes defects in mitotic spindle morphology, including
      misalignment of chromosomes and abnormal numbers of spindle poles. These results
      indicate that the generation of Ran-GTP in the vicinity of chromosomes by RCC1 is
      important for the fidelity of mitotic spindle assembly in human cells. Defects in
      this system may result in abnormal chromosome segregation and genomic
      instability, which are characteristic of many cancer cells.

PMID- 12194827
TI  - Completion of mitosis requires neither fzr/rap nor fzr2, a male germline-specific
      Drosophila Cdh1 homolog.
AB  - Proteolysis of mitotic regulators like securins and cyclins requires
      Fizzy(FZY)/Cdc20 and Fizzy-related(FZR)/Hct1/Cdh1 proteins. Budding yeast Cdh1
      acts not only during G1, but is also required for B-type cyclin degradation
      during exit from mitosis when Cdh1 is a target of the mitotic exit network
      controlling progression through late mitosis and cytokinesis. In contrast,
      observations in frog and Drosophila embryos have suggested that the orthologous
      FZR is not involved during exit from mitosis. However, the potential involvement
      of minor amounts of maternally derived FZR was not excluded in these studies.
      Similarly, the reported absence of severe mitotic defects in chicken Cdh1(-/-)
      cells might be explained by the recent identification of multiple Cdh1 genes
      [10]. Here, we have carefully analyzed the FZR requirement during exit from
      mitosis in Drosophila, which, apart from fzr, has only one additional homolog. We
      find that this fzr2 gene, although expressed in the male germline, is not
      expressed during mitotic divisions. Moreover, by characterizing fzr alleles, we
      demonstrate that completion of mitosis including Cyclin B degradation does not
      require FZR. However, fzr is an essential gene corresponding to the rap locus,
      and FZR, which accumulates predominantly in the cytoplasm, is clearly required
      during G1.

PMID- 12194830
TI  - Widening the net on genome sequencing.
AB  - GENOMES: With the DNA sequencing of most key model organisms finished or well on
      the way, one genomics institute is filling an important niche, using novel
      criteria to take on species from organisms that occupy a unique place in the
      evolutionary tree to others that have an ability to digest explosives.

PMID- 12194831
TI  - Opsins and melanopsins.

PMID- 12194832
TI  - The evolution of longevity.

PMID- 12194833
TI  - Visual cortex: suppression by depression?
AB  - The response of a neuron in the visual cortex to an oriented light bar is
      strongly reduced by concurrent presentation of a stimulus with a different
      orientation. New data suggest this 'cross-orientation suppression' is caused, not
      by intracortical inhibition, but by rapid depression of thalamocortical synapses.

PMID- 12194834
TI  - Ageing: repair and transcription keep us from premature ageing.
AB  - Trichothiodystrophy (TTD) is a complex disorder caused by mutations in the XPD
      gene which affect both DNA repair and transcription. A mouse with a TTD mutation
      has now been found to display remarkable signs of premature ageing.

PMID- 12194835
TI  - Neurophysiology: cerebral carbon copies.
AB  - Predicting the consequences of our actions is essential for sensorimotor control.
      A candidate neural pathway underlying the prediction of eye position during
      saccades has been reported.

PMID- 12194837
TI  - Actin dynamics: the arp2/3 complex branches out.
AB  - Several new findings point to novel functions for the Arp2/3 complex. The
      dendritic nucleation model that has been proposed to describe cell extension for
      locomotion may also be applicable to other actin-based processes.

PMID- 12194836
TI  - B-cell signaling: protein kinase Cdelta puts the brakes on.
AB  - The phenotype of mice lacking the delta isoform of protein kinase C reveals that
      this isoform curtails signaling events after engagement of the antigen-specific
      receptor on B cells. The result is a state of non-responsiveness, termed anergy,
      that represents one form of immunological self-tolerance.

PMID- 12194838
TI  - Axon guidance: proteins turnover in turning growth cones.
AB  - Accurate navigation by a neuronal growth cone requires the modulation of the
      growth cone's responsiveness to spatial and temporal changes in expression of
      guidance cues. These adaptations involve local protein synthesis and turnover in
      growth cones and distal axons.

PMID- 12194839
TI  - Calcium signalling: more messengers, more channels, more complexity.
AB  - Recent studies have expanded the number of channel types and messengers that lead
      to Ca(2+) signals within cells. Furthermore, we are beginning to understand the
      complex interplay between different sources of Ca(2+).

PMID- 12194840
TI  - Ion channels: open at last.
AB  - Previous X-ray studies of have focused on the closed state of the potassium
      channel. Now the structure of a calcium-activated bacterial potassium channel has
      revealed the nature of the channel's open state. This provides a first view at
      high resolution of ion channel gating.

PMID- 12194841
TI  - The fertile field of Drosophila Jak/STAT signalling.
AB  - The JAK/STAT pathway plays important roles in vertebrate and invertebrate
      development. The recent cloning and characterisation of the receptor in
      Drosophila shows that the pathway is conserved across phyla. In this review we
      describe current knowledge of the pathway and use genome data to discuss what
      elements are present in Drosophila. We also summarise recent work describing the
      involvement of the JAK/STAT pathway in oogenesis and spermatogenesis.
      Interestingly, the JAK/STAT pathway maintains the niche required for germline
      stem cell maintenance in the testis, providing the first molecular
      characterisation of a stem cell niche. Drosophila's streamlined pathway offers a
      simple model to find new elements and analyse the function of existing ones.

PMID- 12194842
TI  - Formins: taking a ride on the barbed end.
AB  - Formins are an ancient family of cell polarity regulators. Until recently, they
      were implicated in actin cytoskeleton regulation without a specific molecular
      function. That may all have changed with the publication of new results from
      several labs.

PMID- 12194843
TI  - REV-ving up the clock.
AB  - Circadian rhythms are generated by a transcription/translation feedback loop
      consisting of two limbs, one positive and one negative. The nuclear orphan
      receptor, REV-ERBalpha, is identified as a molecular link coupling these two
      limbs.

PMID- 12194844
TI  - Coupled zones of f-actin and microtubule movement in polarized cells.
AB  - Interactions between the actin and microtubule cytoskeletons occur during cell
      polarization. Two papers in a recent issue of the Journal of Cell Biology use
      fluorescent speckle microscopy (FSM) to analyze the relationship between actin
      and microtubule movements in migrating epithelial cells and in polarizing
      neuronal growth cones.

PMID- 12194845
TI  - Pseudostructural inhibitors of G protein signaling during development.
AB  - Heterotrimeric G proteins mediate signal transduction pathways to control
      development in fungal, plant, and animal cells. A recent study in the July issue
      of Molecular Cell identifies three proteins that, while not displaying sequence
      similarity to G protein subunits, appear to act as structural mimics of a
      Gbetagamma dimer to negatively regulate pseudohyphal growth in budding yeast.

PMID- 12194846
TI  - Numb: "Adapting" notch for endocytosis.
AB  - During sensory organ precursor divisions in Drosophila, the numb gene product
      segregates asymmetrically into one of the two daughter cells, to which it confers
      a specific fate by inhibiting Notch signaling. In this issue of Developmental
      Cell, Berdnik et al. show that Numb recruits alpha-Adaptin and that this physical
      interaction plays a role in downregulating Notch, presumably by stimulating
      endocytosis of Notch.

PMID- 12194847
TI  - Heads or tails: cell polarity and axis formation in the early Caenorhabditis
      elegans embryo.
AB  - In C. elegans, the first embryonic axis is established shortly after
      fertilization and requires both the microtubule and microfilament cytoskeleton.
      Cues from sperm-donated centrosomes result in a cascade of events that polarize
      the distribution of widely conserved PAR proteins at the cell cortex. The PAR
      proteins in turn polarize the cytoplasm and position mitotic spindles. Lessons
      learned from C. elegans should improve our understanding of how cells become
      polarized and divide asymmetrically during development.

PMID- 12194848
TI  - Twenty pairs of sox: extent, homology, and nomenclature of the mouse and human
      sox transcription factor gene families.

PMID- 12194849
TI  - Formation of multiple hearts in mice following deletion of beta-catenin in the
      embryonic endoderm.
AB  - Using Cre/loxP, we conditionally inactivated the beta-catenin gene in cells of
      structures that exhibit important embryonic organizer functions: the visceral
      endoderm, the node, the notochord, and the definitive endoderm. Mesoderm
      formation was not affected in the mutant embryos, but the node was missing,
      patterning of the head and trunk was affected, and no notochord or somites were
      formed. Surprisingly, deletion of beta-catenin in the definitive endoderm led to
      the formation of multiple hearts all along the anterior-posterior (A/P) axis of
      the embryo. Ectopic hearts developed in parallel with the normal heart in regions
      of ectopic Bmp2 expression. We provide evidence that ablation of beta-catenin in
      embryonic endoderm changes cell fate from endoderm to precardiac mesoderm,
      consistent with the existence of bipotential mesendodermal progenitors in mouse
      embryos.

PMID- 12194850
TI  - The PTH/PTHrP receptor can delay chondrocyte hypertrophy in vivo without
      activating phospholipase C.
AB  - One G protein-coupled receptor (GPCR) can activate more than one G protein, but
      the physiologic importance of such activation has not been demonstrated in vivo.
      We have generated mice expressing exclusively a mutant form of the PTH/PTHrP
      receptor (DSEL) that activates adenylyl cyclase normally but not phospholipase C
      (PLC). DSEL mutant mice exhibit abnormalities in embryonic endochondral bone
      development, including delayed ossification and increased chondrocyte
      proliferation. Analysis of the differentiation of embryonic metatarsals in vitro
      shows that PTH(1-34) and forskolin inhibit, whereas active phorbol ester
      stimulates, hypertrophic differentiation. Thus, PLC signaling via the PTH/PTHrP
      receptor normally slows the proliferation and hastens the differentiation of
      chondrocytes, actions that oppose the dominant effects of PTH/PTHrP receptors and
      that involve cAMP-dependent signaling pathways.

PMID- 12194851
TI  - FGF is an essential mitogen and chemoattractant for the air sacs of the
      drosophila tracheal system.
AB  - The Drosophila adult has a complex tracheal system that forms during the pupal
      period. We have studied the derivation of part of this system, the air sacs of
      the dorsal thorax. During the third larval instar, air sac precursor cells bud
      from a tracheal branch in response to FGF, and then they proliferate and migrate
      to the adepithelial layer of the wing imaginal disc. In addition, FGF induces
      these air sac precursors to extend cytoneme-like filopodia to FGF-expressing
      cells. These findings provide evidence that FGF is a mitogen in Drosophila,
      correlate growth factor signaling with filopodial contact between signaling and
      responding cells, and suggest that FGF can act on differentiated tracheal cells
      to induce a novel behavior and role.

PMID- 12194852
TI  - Loss of the ecdysteroid-inducible E75A orphan nuclear receptor uncouples molting
      from metamorphosis in Drosophila.
AB  - Isoform-specific null mutations were used to define the functions of three orphan
      members of the nuclear receptor superfamily, E75A, E75B, and E75C, encoded by the
      E75 early ecdysteroid-inducible gene. E75B mutants are viable and fertile, while
      E75C mutants die as adults. In contrast, E75A mutants have a reduced ecdysteroid
      titer during larval development, resulting in developmental delays, developmental
      arrests, and molting defects. Remarkably, some E75A mutant second instar larvae
      display a heterochronic phenotype in which they induce genes specific to the
      third instar and pupariate without undergoing a molt. We propose that ecdysteroid
      induced E75A expression defines a feed-forward pathway that amplifies or
      maintains the ecdysteroid titer during larval development, ensuring proper
      temporal progression through the life cycle.

PMID- 12194853
TI  - The endocytic protein alpha-Adaptin is required for numb-mediated asymmetric cell
      division in Drosophila.
AB  - During asymmetric cell division in Drosophila sensory organ precursor cells, the
      Numb protein localizes asymmetrically and segregates into one daughter cell,
      where it influences cell fate by repressing signal transduction via the Notch
      receptor. We show here that Numb acts by polarizing the distribution of alpha
      Adaptin, a protein involved in receptor-mediated endocytosis. alpha-Adaptin binds
      to Numb and localizes asymmetrically in a Numb-dependent fashion. Mutant forms of
      alpha-Adaptin that no longer bind to Numb fail to localize asymmetrically and
      cause numb-like defects in asymmetric cell division. Our results suggest a model
      in which Numb influences cell fate by downregulating Notch through polarized
      receptor-mediated endocytosis, since Numb also binds to the intracellular domain
      of Notch.

PMID- 12194854
TI  - A calcium sensor and its interacting protein kinase are global regulators of
      abscisic acid signaling in Arabidopsis.
AB  - The phytohormone abscisic acid (ABA) triggers an oscillation in the cytosolic
      Ca(2+) concentration, which is then perceived by unknown Ca(2+) binding proteins
      to initiate a series of signaling cascades that control many physiological
      processes, including adaptation to environmental stress. We report here that a
      Ca(2+) binding protein, SCaBP5, and its interacting protein kinase, PKS3,
      function as global regulators of ABA responses. Arabidopsis mutants with silenced
      SCaBP5 or PKS3 are hypersensitive to ABA in seed germination, seedling growth,
      stomatal closing, and gene expression. PKS3 physically interacts with the 2C-type
      protein phosphatase ABI2 (ABA-insensitive 2) and to a lesser extent with the
      homologous ABI1 (ABA-insensitive 1) protein. Thus, SCaBP5 and PKS3 are part of a
      calcium-responsive negative regulatory loop controlling ABA sensitivity.

PMID- 12194855
TI  - Lateral propagation of EGF signaling after local stimulation is dependent on
      receptor density.
AB  - We analyzed lateral propagation of epidermal growth factor (EGF) signaling in
      single live COS cells following local stimulation, achieved by the use of laminar
      flows containing rhodamine-labeled EGF. The spatiotemporal pattern of EGF
      signaling was visualized by fluorescent indicators for Ras activation and
      tyrosine phosphorylation. Contrary to the findings in previous reports, both
      signals were localized to the stimulated regions in control COS cells expressing
      EGF receptor at the basal level. However, the signals spread over the entire cell
      when EGF receptors were overexpressed or when receptor/ligand endocytosis was
      blocked. We thus present evidence that ligand-independent propagation of EGF
      signaling occurs only when the receptor density on the plasma membrane is high,
      such as in carcinoma cells.

PMID- 12194856
TI  - Spatio-temporal regulation of Rac1 localization and lamellipodia dynamics during
      epithelial cell-cell adhesion.
AB  - Cadherin-dependent epithelial cell-cell adhesion is thought to be regulated by
      Rho family small GTPases and PI 3-kinase, but the mechanisms involved are poorly
      understood. Using time-lapse microscopy and quantitative image analysis, we show
      that cell-cell contact in MDCK epithelial cells coincides with a spatio-temporal
      reorganization of plasma membrane Rac1 and lamellipodia from noncontacting to
      contacting surfaces. Within contacts, Rac1 and lamellipodia transiently
      concentrate at newest sites, but decrease at older, stabilized sites.
      Significantly, Rac1 mutants alter kinetics of cell-cell adhesion and
      strengthening, but not the eventual generation of cell-cell contacts. Products of
      PI 3-kinase activity also accumulate dynamically at contacts, but are not
      essential for either initiation or development of cell-cell adhesion. These
      results define a role for Rac1 in regulating the rates of initiation and
      strengthening of cell-cell adhesion.

PMID- 12194857
TI  - Escrt-III: an endosome-associated heterooligomeric protein complex required for
      mvb sorting.
AB  - The sorting of transmembrane proteins (e.g., cell surface receptors) into the
      multivesicular body (MVB) pathway to the lysosomal/vacuolar lumen requires the
      function of the ESCRT protein complexes. The soluble coiled-coil-containing
      proteins Vps2, Vps20, Vps24, and Snf7 are recruited from the cytoplasm to
      endosomal membranes where they oligomerize into a protein complex, ESCRT-III.
      ESCRT-III contains two functionally distinct subcomplexes. The Vps20-Snf7
      subcomplex binds to the endosomal membrane, in part via the myristoyl group of
      Vps20. The Vps2-Vps24 subcomplex binds to the Vps20-Snf7 complex and thereby
      serves to recruit additional cofactors to this site of protein sorting. We
      provide evidence for a role for ESCRT-III in sorting and/or concentration of MVB
      cargoes.

PMID- 12194858
TI  - Endosome-associated complex, ESCRT-II, recruits transport machinery for protein
      sorting at the multivesicular body.
AB  - Sorting of ubiquitinated endosomal membrane proteins into the MVB pathway is
      executed by the class E Vps protein complexes ESCRT-I, -II, and -III, and the AAA
      type ATPase Vps4. This study characterizes ESCRT-II, a soluble approximately 155
      kDa protein complex formed by the class E Vps proteins Vps22, Vps25, and Vps36.
      This protein complex transiently associates with the endosomal membrane and
      thereby initiates the formation of ESCRT-III, a membrane-associated protein
      complex that functions immediately downstream of ESCRT-II during sorting of MVB
      cargo. ESCRT-II in turn functions downstream of ESCRT-I, a protein complex that
      binds to ubiquitinated endosomal cargo. We propose that the ESCRT complexes
      perform a coordinated cascade of events to select and sort MVB cargoes for
      delivery to the lumen of the vacuole/lysosome.

PMID- 12194860
TI  - Olfactory axon pathfinding: who is the pied piper?
AB  - Mammalian olfactory sensory neurons that express a particular odorant receptor
      (OR) project axons to the same few glomeruli in the olfactory bulb. In this issue
      of Neuron, Vassalli et al. use OR minigenes that coexpress histochemical markers
      and show that the determinants in the sensory neurons required to generate the
      stereotyped olfactory bulb map are the same as those needed for appropriate
      expression of the OR.

PMID- 12194859
TI  - NPK1, an MEKK1-like mitogen-activated protein kinase kinase kinase, regulates
      innate immunity and development in plants.
AB  - Mitogen-activated protein kinase (MAPK) cascades are rapidly activated upon plant
      recognition of invading pathogens. Here, we describe the use of virus-induced
      gene silencing (VIGS) to study the role of candidate plant MAP kinase kinase
      kinase (MAPKKK) homologs of human MEKK1 in pathogen-resistance pathways. We
      demonstrate that silencing expression of a tobacco MAPKKK, Nicotiana Protein
      Kinase 1 (NPK1), interferes with the function of the disease-resistance genes N,
      Bs2, and Rx, but does not affect Pto- and Cf4-mediated resistance. Further, NPK1
      silenced plants also exhibit reduced cell size, defective cytokinesis, and an
      overall dwarf phenotype. Our results provide evidence that NPK1 functions in the
      regulation of N-, Bs2-, and Rx-mediated resistance responses and may play a role
      in one or more MAPK cascades, regulating multiple cellular processes.

PMID- 12194861
TI  - Phasic transmitter release from tonic neurons.
AB  - Graded and prolonged presynaptic depolarizations trigger the tonic release of
      neurotransmitters from sensory neurons. In this issue of Neuron, Simmons reports
      that postsynaptic responses of locust interneuron synpapses are determined by the
      rate rather than the amplitude of presynaptic depolarization, suggesting a
      mechanism for increasing the signaling capabilities of this synapse with respect
      to visual processing.

PMID- 12194862
TI  - A new mechanism for neuronal gain control (or how the gain in brains has mainly
      been explained).
AB  - One of the more prosaic but necessary features of almost any information
      processing system is gain control. All such systems must have some way to adjust
      the relationship between input, which can vary dramatically depending on changes
      in the environment, and output, which is almost always required to remain within
      a limited range of amplitudes. While the volume control on a radio or the
      brightness control on a computer monitor are not the most exciting or highly
      touted features, imagine such devices without these forms of gain control. Many
      an engineer can attest to the large effort required to design automatic gain
      controls in telephones, cameras, and radio transmitters.

PMID- 12194863
TI  - Function and regulation of CREB family transcription factors in the nervous
      system.
AB  - CREB and its close relatives are now widely accepted as prototypical stimulus
      inducible transcription factors. In many cell types, these factors function as
      effector molecules that bring about cellular changes in response to discrete sets
      of instructions. In neurons, a wide range of extracellular stimuli are capable of
      activating CREB family members, and CREB-dependent gene expression has been
      implicated in complex and diverse processes ranging from development to
      plasticity to disease. In this review, we focus on the current level of
      understanding of where, when, and how CREB family members function in the nervous
      system.

PMID- 12194864
TI  - The human hippocampus and spatial and episodic memory.
AB  - Finding one's way around an environment and remembering the events that occur
      within it are crucial cognitive abilities that have been linked to the
      hippocampus and medial temporal lobes. Our review of neuropsychological,
      behavioral, and neuroimaging studies of human hippocampal involvement in spatial
      memory concentrates on three important concepts in this field: spatial
      frameworks, dimensionality, and orientation and self-motion. We also compare
      variation in hippocampal structure and function across and within species. We
      discuss how its spatial role relates to its accepted role in episodic memory.
      Five related studies use virtual reality to examine these two types of memory in
      ecologically valid situations. While processing of spatial scenes involves the
      parahippocampus, the right hippocampus appears particularly involved in memory
      for locations within an environment, with the left hippocampus more involved in
      context-dependent episodic or autobiographical memory.

PMID- 12194865
TI  - Cell-intrinsic differences between stem cells from different regions of the
      peripheral nervous system regulate the generation of neural diversity.
AB  - Stem cells in different regions of the nervous system give rise to different
      types of mature cells. This diversity is assumed to arise in response to local
      environmental differences, but the contribution of cell-intrinsic differences
      between stem cells has been unclear. At embryonic day (E)14, neural crest stem
      cells (NCSCs) undergo primarily neurogenesis in the gut but gliogenesis in
      nerves. Yet gliogenic and neurogenic factors are expressed in both locations.
      NCSCs isolated by flow-cytometry from E14 sciatic nerve and gut exhibited
      heritable, cell-intrinsic differences in their responsiveness to lineage
      determination factors. Gut NCSCs were more responsive to neurogenic factors,
      while sciatic nerve NCSCs were more responsive to gliogenic factors. Upon
      transplantation of uncultured NCSCs into developing peripheral nerves in vivo,
      sciatic nerve NCSCs gave rise only to glia, while gut NCSCs gave rise primarily
      to neurons. Thus, cell fate in the nerve was stem cell determined.

PMID- 12194866
TI  - Neural crest stem cells persist in the adult gut but undergo changes in self
      renewal, neuronal subtype potential, and factor responsiveness.
AB  - We found neural crest stem cells (NCSCs) in the adult gut. Postnatal gut NCSCs
      were isolated by flow-cytometry and compared to fetal gut NCSCs. They self
      renewed extensively in culture but less than fetal gut NCSCs. Postnatal gut NCSCs
      made neurons that expressed a variety of neurotransmitters but lost the ability
      to make certain subtypes of neurons that are generated during fetal development.
      Postnatal gut NCSCs also differed in their responsiveness to lineage
      determination factors, affecting cell fate determination in vivo and possibly
      explaining their reduced neuronal subtype potential. These perinatal changes in
      gut NCSCs parallel perinatal changes in hematopoietic stem cells, suggesting that
      stem cells in different tissues undergo similar developmental transitions. The
      persistence of NCSCs in the adult PNS opens up new possibilities for regeneration
      after injury or disease.

PMID- 12194867
TI  - FGFR1 is required for the development of the auditory sensory epithelium.
AB  - The mammalian auditory sensory epithelium, the organ of Corti, comprises the hair
      cells and supporting cells that are pivotal for hearing function. The origin and
      development of their precursors are poorly understood. Here we show that loss-of
      function mutations in mouse fibroblast growth factor receptor 1 (Fgfr1) cause a
      dose-dependent disruption of the organ of Corti. Full inactivation of Fgfr1 in
      the inner ear epithelium by Foxg1-Cre-mediated deletion leads to an 85% reduction
      in the number of auditory hair cells. The primary cause appears to be reduced
      precursor cell proliferation in the early cochlear duct. Thus, during
      development, FGFR1 is required for the generation of the precursor pool, which
      gives rise to the auditory sensory epithelium. Our data also suggest that FGFR1
      might have a distinct later role in intercellular signaling within the
      differentiating auditory sensory epithelium.

PMID- 12194868
TI  - Minigenes impart odorant receptor-specific axon guidance in the olfactory bulb.
AB  - An olfactory sensory neuron (OSN) expresses selectively one member from a
      repertoire of approximately 1000 odorant receptor (OR) genes and projects its
      axon to a specific glomerulus in the olfactory bulb. Both processes are here
      recapitulated by MOR23 and M71 OR minigenes, introduced into mice. Minigenes of 9
      kb and as short as 2.2 kb are selectively expressed by neurons that do not
      coexpress the endogenous gene but coproject their axons to the same glomeruli.
      Deletion of a 395 bp upstream region in the MOR23 minigene abolishes expression.
      In this region we recognize sequence motifs conserved in many OR genes.
      Transgenic lines expressing the OR in ectopic epithelial zones form ectopic
      glomeruli, which also receive input from OSNs expressing the cognate endogenous
      receptor. This suggests a recruitment through homotypic interactions between OSNs
      expressing the same OR.

PMID- 12194869
TI  - Akt1 regulates a JNK scaffold during excitotoxic apoptosis.
AB  - Cell survival is determined by a balance among signaling cascades, including
      those that recruit the Akt and JNK pathways. Here we describe a novel interaction
      between Akt1 and JNK interacting protein 1 (JIP1), a JNK pathway scaffold. Direct
      association between Akt1 and JIP1 was observed in primary neurons. Neuronal
      exposure to an excitotoxic stimulus decreased the Akt1-JIP1 interaction and
      concomitantly increased association between JIP1 and JNK. Akt1 interaction with
      JIP1 inhibited JIP1-mediated potentiation of JNK activity by decreasing JIP1
      binding to specific JNK pathway kinases. Consistent with this view, neurons from
      Akt1-deficient mice exhibited higher susceptibility to kainate than wild-type
      littermates. Overexpression of Akt1 mutants that bind JIP1 reduced excitotoxic
      apoptosis. These results suggest that Akt1 binding to JIP1 acts as a regulatory
      gate preventing JNK activation, which is released under conditions of excitotoxic
      injury.

PMID- 12194870
TI  - Arginase I and polyamines act downstream from cyclic AMP in overcoming inhibition
      of axonal growth MAG and myelin in vitro.
AB  - Elevation of cAMP can overcome myelin inhibitors to encourage regeneration of the
      CNS. We show that a consequence of elevated cAMP is the synthesis of polyamines,
      resulting from an up-regulation of Arginase I, a key enzyme in their synthesis.
      Inhibiting polyamine synthesis blocks the cAMP effect on regeneration. Either
      over-expression of Arginase I or exogenous polyamines can overcome inhibition by
      MAG and by myelin in general. While MAG/myelin support the growth of young DRG
      neurons, they become inhibitory as DRGs mature. Endogenous Arginase I levels are
      high in young DRGs but drop spontaneously at an age that coincides with the
      switch from promotion to inhibition by MAG/myelin. Over-expressing Arginase I in
      maturing DRGs blocks that switch. Arginase I and polyamines are more specific
      targets than cAMP for intervention to encourage regeneration after CNS injury.

PMID- 12194872
TI  - Mechanisms regulating variability of the single photon responses of mammalian rod
      photoreceptors.
AB  - Variability in the single photon responses of rod photoreceptors limits the
      accuracy with which the number and timing of photon absorptions are encoded. We
      investigated how much single photon responses of mammalian rods fluctuate and
      what mechanisms control these fluctuations. Mammalian rods, like those of toads,
      generated responses to single photons with trial-to-trial fluctuations 3-4 times
      smaller than other familiar signals produced by single molecules. We used the
      properties of the measured fluctuations to constrain models for how the single
      photon responses are regulated. Neither feedback control of rhodopsin's activity
      nor saturation within the transduction cascade were consistent with experiment.
      The measured responses, however, could be explained by multistep shutoff of
      rhodopsin or a combination of multistep shutoff and saturation.

PMID- 12194871
TI  - cAMP-dependent protein kinase regulates desensitization of the capsaicin receptor
      (VR1) by direct phosphorylation.
AB  - The capsaicin receptor, VR1 (also known as TRPV1), is a ligand-gated ion channel
      expressed on nociceptive sensory neurons that responds to noxious thermal and
      chemical stimuli. Capsaicin responses in sensory neurons exhibit robust
      potentiation by cAMP-dependent protein kinase (PKA). In this study, we
      demonstrate that PKA reduces VR1 desensitization and directly phosphorylates VR1.
      In vitro phosphorylation, phosphopeptide mapping, and protein sequencing of VR1
      cytoplasmic domains delineate several candidate PKA phosphorylation sites.
      Electrophysiological analysis of phosphorylation site mutants clearly pinpoints
      Ser116 as the residue responsible for PKA-dependent modulation of VR1. Given the
      significant roles of VR1 and PKA in inflammatory pain hypersensitivity, VR1
      phosphorylation at Ser116 by PKA may represent an important molecular mechanism
      involved in the regulation of VR1 function after tissue injury.

PMID- 12194873
TI  - Presynaptic depolarization rate controls transmission at an invertebrate synapse.
AB  - Second-order neurons L1-3 of the locust ocellar pathway make inhibitory synapses
      with each other. Although the synapses transmit graded potentials, transmission
      depresses rapidly and completely so that a synapse only transmits when the
      presynaptic terminal depolarizes rapidly. The rate at which a presynaptic neuron
      depolarizes determines the rate at which a postsynaptic neuron hyperpolarizes,
      and neurotransmitter is only released during a fixed 2 ms long period.
      Consequently, the amplitude of a postsynaptic potential depends on the rate
      rather than the amplitude of a presynaptic depolarization. Following a
      postsynaptic potential, a synapse recovers from depression over about a second.
      The synapse recovers from depression even if the presynaptic terminal is held
      depolarized.

PMID- 12194874
TI  - Suppression without inhibition in visual cortex.
AB  - Neurons in primary visual cortex (V1) are thought to receive inhibition from
      other V1 neurons selective for a variety of orientations. Evidence for this
      inhibition is commonly found in cross-orientation suppression: responses of a V1
      neuron to optimally oriented bars are suppressed by superimposed mask bars of
      different orientation. We show, however, that suppression is unlikely to result
      from intracortical inhibition. First, suppression can be obtained with masks
      drifting too rapidly to elicit much of a response in cortex. Second, suppression
      is immune to hyperpolarization (through visual adaptation) of cortical neurons
      responding to the mask. Signals mediating suppression might originate in
      thalamus, rather than in cortex. Thalamic neurons exhibit some suppression;
      additional suppression might arise from depression at thalamocortical synapses.
      The mechanisms of suppression are subcortical and possibly include the very first
      synapse into cortex.

PMID- 12194875
TI  - Gain modulation from background synaptic input.
AB  - Gain modulation is a prominent feature of neuronal activity recorded in behaving
      animals, but the mechanism by which it occurs is unknown. By introducing a
      barrage of excitatory and inhibitory synaptic conductances that mimics conditions
      encountered in vivo into pyramidal neurons in slices of rat somatosensory cortex,
      we show that the gain of a neuronal response to excitatory drive can be modulated
      by varying the level of "background" synaptic input. Simultaneously increasing
      both excitatory and inhibitory background firing rates in a balanced manner
      results in a divisive gain modulation of the neuronal response without
      appreciable signal-independent increases in firing rate or spike-train
      variability. These results suggest that, within active cortical circuits, the
      overall level of synaptic input to a neuron acts as a gain control signal that
      modulates responsiveness to excitatory drive.

PMID- 12194877
TI  - Differential effects of viewpoint on object-driven activation in dorsal and
      ventral streams.
AB  - Using fMRI, we showed that an area in the ventral temporo-occipital cortex (area
      vTO), which is part of the human homolog of the ventral stream of visual
      processing, exhibited priming for both identical and depth-rotated images of
      objects. This pattern of activation in area vTO corresponded to performance in a
      behavioral matching task. An area in the caudal part of the intraparietal sulcus
      (area cIPS) also showed priming, but only with identical images of objects. This
      dorsal-stream area treated rotated images as new objects. The difference in the
      pattern of priming-related activation in the two areas may reflect the respective
      roles of the ventral and dorsal streams in object recognition and object-directed
      action.

PMID- 12194876
TI  - Color perception is mediated by a plastic neural mechanism that is adjustable in
      adults.
AB  - An intensely debated issue concerning visual-experience-dependent neural
      plasticity is whether experience is required only to maintain function or whether
      information from experience is used actively, relieving the necessity to hard
      wire all connections and allowing adaptive adjustments. Here, an active role for
      experience is demonstrated in circuits for color vision. Chromatic experience was
      altered using colored filters. Over days there was a shift in color perception,
      as measured by the wavelength of unique yellow, which persisted 1-2 weeks after
      the filters were discontinued. Moreover, color-deficient adults were shown to
      have altered weightings of inputs to chromatic channels, demonstrating a large
      neural adjustment to their inherited photopigment defect. Thus, a neural
      normalization mechanism for color perception, determined by visual experience,
      operates to compensate for large genetic differences in retinal architecture and
      for changes in chromatic environment.

PMID- 12194878
TI  - Common prefrontal regions coactivate with dissociable posterior regions during
      controlled semantic and phonological tasks.
AB  - One of the most ubiquitous findings in functional neuroimaging research is
      activation of left inferior prefrontal cortex (LIPC) during tasks requiring
      controlled semantic retrieval. Here we show that LIPC participates in the
      controlled retrieval of nonsemantic representations as well as semantic
      representations. Results also demonstrate that LIPC coactivates with dissociable
      posterior regions depending on the information retrieved: activating with left
      temporal cortex during the controlled retrieval of semantics and with left
      posterior frontal and parietal cortex during the controlled retrieval of
      phonology. Correlation of performance to LIPC activation suggests a processing
      role associated with mapping relatively ambiguous stimulus-to-representation
      relationships during both semantic and phonological tasks. These findings suggest
      that LIPC participates in controlled processing across multiple information
      domains collaborating with dissociable posterior regions depending upon the kind
      of information retrieved.

PMID- 12194879
TI  - Introduction--environmental air toxics: role in asthma occurrence?

PMID- 12194880
TI  - Environmental air toxics: role in asthma occurrence?
AB  - The National Urban Air Toxics Research Center (NUATRC) hosted its first
      scientific workshop in 1994 that focused on possible relationships between air
      toxics and asthma. From that meeting came recommendations for future research
      including a need for more complete individual personal exposure assessments so
      that determinations of personal exposures to pollutants could be made. In the
      spring of 2001, NUATRC held a second such workshop to review progress made in
      this area during the intervening 7 years. Peer-reviewed articles from the
      workshop are published in this issue of (italic)Environmental Health Perspectives
      Supplements(/italic). As in 1994, academic, government, and industry scientists
      participated. Dave Guinnup of the Environmental Protection Agency discussed the
      nature of air toxics, their definition, and the basis for federal regulation.
      George Leikauf from the University of Cincinnati reviewed the 1994 workshop and
      subsequent research in this field. Current research funded by NUATRC that is
      addressing individual personal exposure was presented by Clifford Weisel
      (Environmental and Occupational Health Sciences Institute, University of Medicine
      and Dentistry of New Jersey), Patrick Kinney (Columbia University) and Candis
      Claiborn (Washington State University). David Corry from Baylor College of
      Medicine highlighted new insights into asthma pathogenesis while Stephen Redd
      from the Centers for Disease Control presented an overview of asthma epidemiology
      as well as the societal costs of the disease. Mary White (Agency for Toxic
      Substances and Disease Registry) discussed recent epidemiologic investigations by
      public health agencies into community concerns about asthma and hazardous air
      pollutants. David Peden (University of North Carolina) reviewed scientific
      studies into the links between asthma and air toxics as well as criteria air
      pollutants. In a session on occupational asthma, Lee Petsonk (National Institute
      for Occupational Safety and Health) discussed risk factors for work-related
      asthma, whereas Ralph Delfino (University of California, Irvine) addressed
      limitations of extrapolating from occupational asthma to asthma in the general
      population. These presentations were followed by panel discussions focusing on
      future research programs, both for NUATRC and similar research institutions.
      Recommendations for future research included improved assessments of personal
      exposure to air toxics as well as research focused on specific hazardous air
      pollutants. The latter recommendation was based on medical literature that
      suggests certain pollutants from the list of 188 air toxics are most likely to
      adversely affect respiratory health.

PMID- 12194882
TI  - Assessing exposure to air toxics relative to asthma.
AB  - Asthma is a respiratory disease whose prevalence has been increasing since the
      mid 1970s and that affects more than 14.6 million residents of the United States.
      Environmental triggers of asthma include air pollutants that are respiratory
      irritants. Air toxics emitted into the ambient air are listed in the 1990 Clean
      Air Act Amendments as hazardous air pollutants (HAPs) if they can adversely
      affect human health, including the respiratory tract. HAPs include particulate
      and gaseous-phase pollutants, individual organic compounds and metals, and
      mixtures. Associations between asthma exacerbation and both particles and indoor
      volatile organic compounds (VOCs), often referred to as indoor air quality, have
      been reported. Studies conducted in the United States, Canada, and Europe over
      the past two decades have shown that most people living in the developed
      countries spend the majority of their time indoors and that the air
      concentrations of many air toxics or HAPs are higher indoors than in the ambient
      air in urban, suburban, and rural settings. Elevated indoor air concentrations
      result from emissions of air toxics from consumer products, household
      furnishings, and personal activities. The Relationship of Indoor, Outdoor and
      Personal Air (RIOPA) study was designed to oversample homes in close proximity to
      ambient sources, excluding residences where smokers lived, to determine the
      contribution of ambient emissions to air toxics exposure. The ratios of indoor to
      outdoor air concentrations of some VOCs in homes measured during RIOPA were much
      greater than one, and for most other VOCs that had indoor-to-outdoor ratios close
      to unity in the majority of homes, elevated ratios were found in the paired
      samples with the highest concentration. Thus, although ambient emissions
      contribute to exposure of some air toxics indoors as well as outdoors, this was
      not true for all of the air toxics and especially for the higher end of exposures
      to most volatile organic air toxics examined. It is therefore critical, when
      evaluating potential effects of air toxics on asthma or other adverse health end
      points, to determine where the exposure occurs and the source contributions for
      each air toxic and target population separately and not to rely solely on ambient
      air concentration measurements.

PMID- 12194883
TI  - Exposures to multiple air toxics in New York City.
AB  - Efforts to assess health risks associated with exposures to multiple urban air
      toxics have been hampered by the lack of exposure data for people living in urban
      areas. The TEACH (Toxic Exposure Assessment, a Columbia/Harvard) study was
      designed to characterize levels of and factors influencing personal exposures to
      urban air toxics among high school students living in inner-city neighborhoods of
      New York City and Los Angeles, California. This present article reports methods
      and data for the New York City phase of TEACH, focusing on the relationships
      between personal, indoor, and outdoor concentrations in winter and summer among a
      group of 46 high school students from the A. Philip Randolph Academy, a public
      high school located in the West Central Harlem section of New York City. Air
      pollutants monitored included a suite of 17 volatile organic compounds (VOCs) and
      aldehydes, particulate matter with a mass median aerodynamic diameter <or= 2.5
      microm (PM2.5), black carbon, and a suite of 28 particle-associated trace
      elements. Sequential 48-hr ambient samples also were collected over 8 weeks in
      each season at an urban fixed site and an upwind, nonurban fixed site. Personal,
      indoor, and outdoor concentrations of particle elements were generally similar,
      suggesting that ambient sources may have driven indoor and personal exposures for
      most elements. More varied relationships among personal, home indoor, and home
      outdoor concentrations were observed for VOCs and aldehydes. For formaldehyde and
      acetaldehyde, and several VOCs, indoor concentrations far exceeded outdoor levels
      and appeared to dominate personal exposures. Strong seasonal differences in
      indoor to outdoor concentration ratios were observed for these compounds,
      reflecting the influence of home air exchange rates. For other VOCs, especially
      those related to motor vehicle exhaust, more consistent indoor, outdoor, and
      personal concentrations were observed, suggesting that ambient concentrations may
      have been the driving force for personal exposures to some VOCs. These results
      demonstrate exposures to a wide range of air toxic pollutants among young people
      attending school in inner-city New York.

PMID- 12194884
TI  - Testing the metals hypothesis in Spokane, Washington.
AB  - A >7-year, time-series, epidemiologic study is ongoing in Spokane, Washington, to
      examine the associations between ambient particulate constituents or sources and
      health outcomes such as emergency department (ED) visits for asthma or
      respiratory problems. One of the hypotheses being tested is that particulate
      toxic metals are associated with these health outcomes. Spokane is a desirable
      city in which to conduct this study because of its relatively high concentrations
      of particulate matter, low concentrations of potentially confounding air
      pollutants, variability of particulate sources, and presence of several potential
      particulate metals sources. Daily fine- and coarse-fraction particulate samples
      are analyzed for metals via energy-dispersive X-ray fluorescence (EDXRF) and
      instrumental neutron activation analysis. Particulate sources are determined
      using receptor modeling, including chemical mass balancing and positive matrix
      factorization coupled with partial source contribution function analysis.
      Principal component analysis has also been used to examine the influence of
      sources on the daily variability of the chemical composition of particulate
      samples. Based upon initial analyses using the EDXRF elemental analyses,
      statistically significant associations were observed between ED visits for asthma
      and increased combustion products, air stagnation, and fine particulate Zn.
      Although there is a significant soil particulate component, increased crustal
      particulate levels were not found to be associated with ED visits for asthma.
      Further research will clarify whether there is an association between specific
      health outcomes and either coarse or fine particulate metal species.

PMID- 12194885
TI  - Environmental contributions to the allergic asthma epidemic.
AB  - Current data overwhelmingly document the existence of a worldwide asthma
      epidemic, although individual studies remain controversial. The epidemic is
      thought to involve primarily persons with allergic asthma, and many diverse
      theories, based on an immunopathologic understanding of disease, have recently
      emerged to explain this involvement. In the context of recent insights into the
      immune basis of experimental asthma, we discuss in this review the leading asthma
      epidemic theories, including a new theory based on inhaled environmental
      proteases. Although no single theory may yet be fully embraced, there exists
      substantial hope that a unifying mechanism for the epidemic will be revealed
      through additional research.

PMID- 12194886
TI  - Asthma in the United States: burden and current theories.
AB  - Asthma has emerged as a major public health problem in the United States over the
      past 20 years. Currently, nearly 15 million Americans have asthma, including
      almost 5 million children. The number of asthma cases has more than doubled since
      1980. Approximately 5,500 persons die from asthma each year, and rates have
      increased over the past 20 years. Rates of death, hospitalization, and emergency
      department visits are 2-3 times higher among African Americans than among white
      Americans. The costs of asthma have also increased to 12.7 billion dollars in
      1998. Both lifestyle and environmental hypotheses have been invoked to explain
      the increase in asthma prevalence. Several studies have examined the relationship
      of obesity and asthma and found associations suggesting that obesity predisposes
      to the development of asthma. Some studies have found that day care attendance
      and having older siblings protect against the development of asthma. This
      observation has led investigators to hypothesize that increased exposure to
      microbial agents might protect against asthma (the hygiene hypothesis).
      Environmental exposures found to predispose to asthma include house dust mite
      allergen and environmental tobacco smoke. Although current knowledge does not
      permit definitive conclusions about the causes of asthma onset, better adherence
      to current recommendations for medical therapy and environmental management of
      asthma would reduce the burden of this disease.

PMID- 12194887
TI  - Addressing community concerns about asthma and air toxics.
AB  - People with asthma who live near or downwind from a source of toxic emissions
      commonly express concerns about the possible impact of hazardous air pollution on
      their health, especially when these emissions are visible or odorous. Citizens
      frequently turn to their local and state health departments for answers, but
      health departments face many challenges in addressing these concerns. These
      challenges include a lack of asthma statistics at the local level, limited
      exposure information, and a paucity of scientific knowledge about the
      contributions of hazardous air pollutants to asthma induction or exacerbation.
      Health agencies are creatively developing methods to address these challenges
      while working toward improving asthma surveillance data at the state and local
      levels. Recent community health investigations suggest that hazardous air
      pollutants that are occupational asthmagens or associated with odors may deserve
      more attention. In seeking to address community concerns about hazardous air
      pollution and asthma, community health investigations may also help to fill gaps
      in our scientific knowledge and identify areas for further research or
      environmental intervention. The solutions to community problems associated with
      environmental contamination and asthma, however, require sustained, coordinated
      efforts by public and private groups and citizens. Public health agencies can
      make a unique contribution to this effort, but additional resources and support
      will be required to develop information systems and epidemiologic capacity at the
      state and local levels.

PMID- 12194888
TI  - Pollutants and asthma: role of air toxics.
AB  - Asthma is a disease characterized by intermittent bronchoconstriction due to
      increased airway reactivity to both allergic and nonallergic stimuli. Most asthma
      exacerbations that result in hospitalization are associated with viral upper
      respiratory tract infections. Such infections typically induce T-helper type 1
      (T(H)1) responses in the airway, involving activation of nuclear factor-kappaB
      (NF-Kappa B). However, a more recently appreciated cause of asthma exacerbation
      is exposure to pollutants, including ozone and various components of particulate
      matter (PM), including transition metals, diesel exhaust, and biologicals such as
      endotoxin. Although the role of air toxics in asthma pathogenesis remains
      incompletely examined, many components of PM that are active exacerbants of
      asthma are also prominent air toxics (metal ions and organic residues). These
      agents have been observed to activate NF-Kappa B. Reviewed in this article are
      the actions of specific air pollutants on airway inflammation in humans and
      potential common response pathways for ozone, PM, and several air toxics.

PMID- 12194881
TI  - Hazardous air pollutants and asthma.
AB  - Asthma has a high prevalence in the United States, and persons with asthma may be
      at added risk from the adverse effects of hazardous air pollutants (HAPs).
      Complex mixtures (fine particulate matter and tobacco smoke) have been associated
      with respiratory symptoms and hospital admissions for asthma. The toxic
      ingredients of these mixtures are HAPs, but whether ambient HAP exposures can
      induce asthma remains unclear. Certain HAPs are occupational asthmagens, whereas
      others may act as adjuncts during sensitization. HAPs may exacerbate asthma
      because, once sensitized, individuals can respond to remarkably low
      concentrations, and irritants lower the bronchoconstrictive threshold to
      respiratory antigens. Adverse responses after ambient exposures to complex
      mixtures often occur at concentrations below those producing effects in
      controlled human exposures to a single compound. In addition, certain HAPs that
      have been associated with asthma in occupational settings may interact with
      criteria pollutants in ambient air to exacerbate asthma. Based on these
      observations and past experience with 188 HAPs, a list of 19 compounds that could
      have the highest impact on the induction or exacerbation of asthma was developed.
      Nine additional compounds were identified that might exacerbate asthma based on
      their irritancy, respirability, or ability to react with biological
      macromolecules. Although the ambient levels of these 28 compounds are largely
      unknown, estimated exposures from emissions inventories and limited air
      monitoring suggest that aldehydes (especially acrolein and formaldehyde) and
      metals (especially nickel and chromium compounds) may have possible health risk
      indices sufficient for additional attention. Recommendations for research are
      presented regarding exposure monitoring and evaluation of biologic mechanisms
      controlling how these substances induce and exacerbate asthma.

PMID- 12194889
TI  - Work-related asthma and implications for the general public.
AB  - Asthma has been increasing over the last two decades in the United States. The
      onset of asthma has also been increasingly reported as a result of occupational
      exposures to over 350 different agents. Work-related asthma (WRA) has become the
      most frequently diagnosed occupational respiratory illness. Epidemiologic studies
      from the United States reported WRA incidence rates of 29-710 cases per million
      workers per year and suggest that 10-25% of adult asthma is work related. Much
      can be learned about asthma in the general population from investigations of
      asthma in the workplace. Surveillance of WRA continues to highlight an important
      role for low molecular weight chemical sensitizers, as well as high molecular
      weight antigens. Additionally, recent reports implicate mixed exposures,
      including commercial cleaning solutions, solvents, and other respiratory
      irritants, as well as contamination in nonindustrial environments, including
      schools and offices. Investigations of WRA have demonstrated a clear dose-related
      increase in sensitization and symptoms for exposures to both chemical and protein
      sensitizers. High proportions of exposed working groups can be affected. Skin
      exposures may affect the likelihood of individuals developing respiratory
      symptoms. Atopy increases the risk of sensitization and illness from workplace
      exposure to antigens but not to chemical sensitizers. Irritant exposures can act
      as adjuvants among individuals exposed to sensitizing substances, increasing the
      proportion who become sensitized. Atopy might also be a result of irritant
      exposures in some persons. Occupational asthma often has important long-term
      adverse health and economic consequences but can resolve completely with timely
      control of exposures. Detailed study of such asthma "cures" may prove useful in
      understanding factors that influence asthmatic airway inflammation in the general
      population.

PMID- 12194891
TI  - The role of environmental factors in medically unexplained symptoms and related
      syndromes: conference summary and recommendations.
AB  - This monograph of peer-reviewed articles is based on presentations at the
      conference "Environmental Factors in Medically Unexplained Physical Symptoms and
      Related Syndromes" held 10-12 January 2001 in Piscataway, New Jersey, USA. The
      purpose of the conference was to determine research priorities for elucidating
      the role of environmental factors in medically unexplained symptoms and symptom
      syndromes. These include conditions such as chronic fatigue syndrome, multiple
      chemical sensitivities, sick building syndrome, Gulf War illness, and the like.
      Approximately 1 1/2 days were devoted to plenary talks and 1 day was devoted to
      break-out sessions to discuss epidemiologic, psychosocial, and experimental
      research. Recommendations were made for a series of epidemiologic, psychosocial,
      and experimental research approaches, with acknowledgment that nosology issues
      are clearly fundamental to advancing understanding of these conditions.

PMID- 12194892
TI  - Environmental factors in medically unexplained symptoms and related syndromes:
      the evidence and the challenge.
AB  - Symptoms, and especially those without clear underlying medical explanations,
      account for a large percentage of clinical encounters. Many unexplained symptoms
      have been organized by patients and practitioners into syndromes such as chronic
      fatigue syndrome, multiple chemical sensitivity, sick building syndrome, Gulf War
      syndrome, and the like. All these syndromes are defined solely on the basis of
      symptoms rather than by medical signs. Some of the above-described conditions
      overlap strongly with explained conditions such as asthma. The relationship of
      such symptoms and syndromes to environmental exposure is often sharply debated,
      as is the distinction between the various syndromes. This leads to problems of
      what type of research should be conducted and who should conduct it. It is time
      to develop a comprehensive research agenda to sort out nomenclature,
      epidemiology, and environmental causation for these conditions, moving toward
      comprehensive and effective public health and clinical approaches.

PMID- 12194890
TI  - Epidemiologic evidence for asthma and exposure to air toxics: linkages between
      occupational, indoor, and community air pollution research.
AB  - Outdoor ambient air pollutant exposures in communities are relevant to the acute
      exacerbation and possibly the onset of asthma. However, the complexity of
      pollutant mixtures and etiologic heterogeneity of asthma has made it difficult to
      identify causal components in those mixtures. Occupational exposures associated
      with asthma may yield clues to causal components in ambient air pollution because
      such exposures are often identifiable as single-chemical agents (e.g., metal
      compounds). However, translating occupational to community exposure-response
      relationships is limited. Of the air toxics found to cause occupational asthma,
      only formaldehyde has been frequently investigated in epidemiologic studies of
      allergic respiratory responses to indoor air, where general consistency can be
      shown despite lower ambient exposures. The specific volatile organic compounds
      (VOCs) identified in association with occupational asthma are generally not the
      same as those in studies showing respiratory effects of VOC mixtures on
      nonoccupational adult and pediatric asthma. In addition, experimental evidence
      indicates that airborne polycyclic aromatic hydrocarbon (PAH) exposures linked to
      diesel exhaust particles (DEPs) have proinflammatory effects on airways, but
      there is insufficient supporting evidence from the occupational literature of
      effects of DEPs on asthma or lung function. In contrast, nonoccupational
      epidemiologic studies have frequently shown associations between allergic
      responses or asthma with exposures to ambient air pollutant mixtures with PAH
      components, including black smoke, high home or school traffic density
      (particularly truck traffic), and environmental tobacco smoke. Other particle
      phase and gaseous co-pollutants are likely causal in these associations as well.
      Epidemiologic research on the relationship of both asthma onset and exacerbation
      to air pollution is needed to disentangle effects of air toxics from monitored
      criteria air pollutants such as particle mass. Community studies should focus on
      air toxics expected to have adverse respiratory effects based on biological
      mechanisms, particularly irritant and immunological pathways to asthma onset and
      exacerbation.

PMID- 12194893
TI  - Models of unexplained symptoms associated with occupational and environmental
      exposures.
AB  - Unexplained illnesses characterized by nonspecific, multisystem complaints are
      often attributed to occupational or environmental chemical exposures. This raises
      difficulties for the regulatory authorities, who are frequently unable to agree
      on the existence, nature, or source of such illnesses. It is proposed that many
      of these difficulties derive from an adherence to a traditional medical model of
      disease and that the application of a biopsychosocial approach would be more
      effective for both research and individual case management. A number of models
      derived from the field of health psychology are discussed in terms of their
      application to occupational and environmental syndromes. A specific example is
      described that relates to the health problems experienced by sheep farmers in the
      United Kingdom who are exposed to organophosphate-based pesticides. The source of
      their complaints and the responses of the health professionals and the regulatory
      authorities are discussed within the context of a biopsychosocial approach that
      focuses on illness rather than on organic disease as the unit of study and
      explores the interaction between the various physical and psychosocial variables
      involved. It is proposed that this approach, which is already well established in
      the fields of human and social sciences, should be adopted more readily by those
      concerned with occupational and environmental epidemiology.

PMID- 12194894
TI  - Contributions of societal and geographical environments to "chronic Lyme
      disease": the psychopathogenesis and aporology of a new "medically unexplained
      symptoms" syndrome.
AB  - Lyme disease is a relatively well-described infectious disease with multisystem
      manifestations. Because of confusion over conflicting reports, anxiety related to
      vulnerability to disease, and sensationalized and inaccurate lay media coverage,
      a new syndrome, "chronic Lyme disease," has become established. Chronic Lyme
      disease is the most recent in a continuing series of "medically unexplained
      symptoms" syndromes. These syndromes, such as fibromyalgia, chronic fatigue
      syndrome, and multiple chemical sensitivity, meet the need for a societally and
      morally acceptable explanation for ill-defined symptoms in the absence of
      objective physical and laboratory findings. We describe factors involved in the
      psychopathogenesis of chronic Lyme disease and focus on the confusion and
      insecurity these patients feel, which gives rise to an inability to adequately
      formulate and articulate their health concerns and to deal adequately with their
      medical needs, a state of disorganization termed aporia.

PMID- 12194895
TI  - Hypersensitivity of human subjects to environmental electric and magnetic field
      exposure: a review of the literature.
AB  - Hypersensitivity to exposure to electric and magnetic fields (EMFs) has been
      reported for nearly 20 years; however, the literature on the subject is still
      very limited. Nearly all the literature published concerns a dermatological
      syndrome that consists of mainly subjective symptoms (itching, burning, dryness)
      and a few objective symptoms (redness, dryness) appearing after individuals begin
      working with video display units and decreasing during absence from work. Case
      control studies as well as some good but limited double-blind trials have not
      found any clear relationship between this syndrome and exposure to EMFs. A
      "general syndrome" with more general symptoms has been rarely described but seems
      to have a worse prognosis. The symptoms often associated with skin disorders are
      mainly of neurasthenic type and can cover a lot of nonspecific symptoms present
      in other atypical syndromes such as multiple chemical sensitivity or chronic
      fatigue. Most of these symptoms are allegedly triggered by exposure to different
      sources of EMFs, but there have been no valid etiological studies published on
      this more general syndrome. It appears that the so-called hypersensitivity to
      environmental electric and magnetic fields is an unclear health problem whose
      nature has yet to be determined.

PMID- 12194896
TI  - Study of self-reported hypersensitivity to electromagnetic fields in California.
AB  - Cases of alleged hypersensitivity to electromagnetic fields (EMFs) have been
      reported for more than 20 years, and some authors have suggested some connection
      with the "multiple chemical sensitivity" illness. We report the results of a
      telephone survey among a sample of 2,072 Californians. Being "allergic or very
      sensitive" to being near electrical devices was reported by 68 subjects,
      resulting in an adjusted prevalence of 3.2% (95% confidence interval = 2.8, 3.7).
      Twenty-seven subjects (1.3%) reported sensitivity to electrical devices but no
      sensitivity to chemicals. Characteristics of the people reporting
      hypersensitivity to EMFs were generally different from those of people reporting
      being allergic to everyday chemicals. Alleging environmental illness or multiple
      chemical sensitivity diagnosed by a doctor was the strongest predictor of
      reporting being hypersensitive to EMFs in this population. Other predictive
      factors apart from self-reporting chemical sensitivity were race/ethnicity other
      than White, Black, or Hispanic; having low income; and being unable to work. The
      perception of risk of exposure to EMFs through the use of hair dryers (vs.
      exposure to power and distribution lines) was the factor the most associated with
      self-reporting about hypersensitivity to EMFs. However, risk perception was not
      sufficient to explain the characteristics of people reporting this disorder.

PMID- 12194897
TI  - Somatic symptoms in women 11 years after the Chornobyl accident: prevalence and
      risk factors.
AB  - Exposure to the Chornobyl nuclear power plant explosion resulted in widespread,
      persistent somatic complaints, but little is known about the nature and risk
      factors for these conditions. This study compares the health reports of 300 women
      evacuated to Kyiv from the contamination zone around the plant and 300 controls
      with a child in the same homeroom as the evacuees in 1997. The interview
      addressed somatic concerns, risk factors for poor health, and Chornobyl-related
      stress. Compared with controls, evacuees reported significantly more health
      problems and rated their health more poorly overall. These differences remained
      significant after controlling for demographic and clinical risk factors,
      including the tendency to amplify physical symptoms. Significantly more evacuees
      received a diagnosis of a Chornobyl-related illness by a local physician,
      believed that their health and their children's health had been adversely
      affected, and were positive for Chornobyl-induced post-traumatic stress disorder.
      After controlling for these Chornobyl stress variables, the differences in number
      of health problems commonly attributed to Chornobyl remained significant but
      differences in general health ratings did not. The perceptions of controls were
      similar to those of women in a national sample. The relationship between
      Chornobyl stress and illness was twice as strong in evacuees (odds ratio = 6.95)
      as in Kyiv controls (odds ratio = 3.34) and weakest in the national sample (odds
      ratio = 1.64). The results confirm the persistence and nonspecificity of the
      subjective medical consequences of Chornobyl and are consistent with the
      hypothesis that traumatic events exert their greatest negative impacts on health
      in vulnerable or disadvantaged groups.

PMID- 12194898
TI  - Medically unexplained physical symptoms in medical practice: a psychiatric
      perspective.
AB  - Clusters of medically unexplained physical symptoms have been referred to in the
      literature by many different labels, including somatization, symptom-based
      conditions, and functional somatic syndromes, among many others. The traditional
      medical perspective has been to classify and study these symptoms and functional
      syndromes separately. In psychiatry, current taxonomies (Diagnostic and
      Statistical Manual of Mental Disorder, 4th edition, and The International
      Statistical Classification of Diseases and Related Health Problems, 10th
      revision) classify these syndromes together under the rubric of somatoform
      disorders. In this article we approach medically unexplained physical symptoms
      from a psychiatric perspective and discuss the common features that unite
      multiple unexplained symptoms or functional somatic syndromes as a class.
      Included in this article is a discussion of nosological issues, clinical
      assessment, how these syndromes are viewed within the various medical
      specialties, and clinical management and treatment.

PMID- 12194899
TI  - Somatization in survivors of catastrophic trauma: a methodological review.
AB  - The literature on mental health effects of catastrophic trauma such as community
      disasters focuses on posttraumatic stress disorder. Somatization disorder is not
      listed among the classic responses to disaster, nor have other somatoform
      disorders been described in this literature. Nondiagnostic "somatization,"
      "somatization symptoms," and "somatic symptoms" form the basis of most
      information about somatization in the literature. However, these concepts have
      not been validated, and therefore this work suffers from multiple methodological
      problems of ascertainment and interpretation. Future research is encouraged to
      consider many methodological issues in obtaining adequate data to address
      questions about the association of somatization with traumatic events, including
      a) appropriate comparison groups, b) satisfactory definition and measurement of
      somatization, c) exclusion of medical explanations for the symptoms, d)
      recognition of somatizers' spurious attribution of symptoms to medical causes, e)
      collection of data from additional sources beyond single-subject interviews, f)
      validation of diagnosis-unrelated symptom reporting or reconsideration of
      symptoms within diagnostic frameworks, g) separation of somatization after an
      event into new (incident) and preexisting categories, h) development of research
      models that include sufficient variables to examine the broader scope of
      potential relationships, and i) novel consideration of alternative causal
      directionalities.

PMID- 12194900
TI  - Caring for medically unexplained physical symptoms after toxic environmental
      exposures: effects of contested causation.
AB  - Medically unexplained physical symptoms (MUPS) are persistent idiopathic symptoms
      that drive patients to seek medical care. MUPS syndromes include chronic fatigue
      syndrome, fibromyalgia syndrome, and multiple chemical sensitivities. When MUPS
      occur after an environmental exposure or injury, an adversarial social context
      that we call "contested causation" may ensue. Contested causation may occur
      publicly and involve media controversy, scientific disagreement, political
      debate, and legal struggles. This adversarial social context may diminish the
      effectiveness of the provider-patient relationship. Contested causation also may
      occur privately, when disagreement over the causes of MUPS takes place in the
      patient-provider context. These patient-provider disagreements over causation
      often occur because of the enigmatic nature of MUPS. We suggest that a context of
      contested causation may have serious negative effects on healthcare for
      individuals with MUPS. Context plays a larger role in MUPS care than it does for
      most medical care because of the uncertain nature of MUPS, the reliance of
      standard MUPS therapies on a potentially tenuous patient-provider partnership,
      and the clinical need to rely routinely on subjective MUPS assessments that often
      yield discordant patient and provider conclusions. Contested causation may erode
      patient-provider trust, test the provider's self-assurance and capacity to share
      power with the patient, and raise problematic issues of compensation, reparation,
      and blame. These issues may distract patients and providers from therapeutic
      goals. In occupational and military settings, the adverse impact of contested
      causation on the patient-provider partnership may diminish therapeutic
      effectiveness to a greater degree than it does in other medical settings.
      Contested causation therefore raises questions regarding generalizability of
      standard therapies for MUPS and related syndromes to these settings. Future
      research is needed to learn whether intuitively sensible and evidence-based MUPS
      therapies benefit occupational and military medical patients who are afforded
      care in the context of contested causation.

PMID- 12194901
TI  - Review of the upper airway, including olfaction, as mediator of symptoms.
AB  - The upper airway serves as air conditioner, filter, and warning device. Two
      neurological modalities, olfaction and trigeminal chemoreception, inform us of
      the chemical qualities of the air we breathe. A number of poorly understood
      conditions, including nonallergic rhinitis, irritant-induced rhinitis, odor
      triggered asthma, odor-triggered panic attacks, chemical-induced olfactory
      dysfunction, and irritant-associated vocal cord dysfunction, involve induction of
      symptoms by odorant and/or irritant chemicals in the upper airway. This article
      is a summary of the knowledge and theories about these various conditions, and
      highlights those aspects of nasal anatomy, physiology, and pathophysiology
      relevant to their understanding.

PMID- 12194902
TI  - The vomeronasal organ and chemical sensitivity: a hypothesis.
AB  - Environmental exposures to very low levels of airborne chemicals are associated
      with adverse symptoms, often affecting multiple organ systems, in the phenomenon
      of chemical sensitivity (CS). Recent surveys suggest a significant prevalence of
      chemically sensitive subjects in the United States, but the mechanism linking
      exposure to symptoms remains unclear, despite the advancement of a variety of
      theoretical models. In many of these models, exposure of the nasal respiratory
      system to an airborne agent is the first step in the pathway leading to symptoms.
      In this article, we advance the hypothesis that interactions between
      environmental chemicals and the vomeronasal organ (VNO) may play a role in the
      etiology of CS. The VNO, a bilateral, tubular organ located in the nose, serves
      in animals as part of a sensitive chemosensory system; however, evidence
      suggesting that the VNO retains a functional role in the adult human is
      controversial. Reported characteristics of the human VNO relevant to CS,
      including location, prevalence, selective sensitivity to airborne chemical
      exposure, and capacity to produce systemic effects, are discussed within the
      context of this ongoing debate. Beyond relevance to CS, the demonstration of an
      active, adult VNO could have significant impact on environmental toxicology.

PMID- 12194904
TI  - Responses to panic induction procedures in subjects with multiple chemical
      sensitivity/idiopathic environmental intolerance: understanding the relationship
      with panic disorder.
AB  - Idiopathic environmental intolerance (IEI), also known as multiple chemical
      sensitivity, is a clinical description for a cluster of symptoms of unknown
      etiology that have been attributed by patients to multiple environmental
      exposures when other medical explanations have been excluded. Because allergy has
      not been clearly demonstrated and current toxicological paradigms for exposure
      symptom relationships do not readily accommodate IEI, psychogenic theories have
      been the focus of a number of investigations. A significantly higher lifetime
      prevalence of major depression, mood disorders, anxiety disorders, and
      somatization disorder has been reported among patients with environmental illness
      compared with that in controls. Symptoms often include anxiety, lightheadedness,
      impaired mentation, poor coordination, breathlessness (without wheezing), tremor,
      and abdominal discomfort. Responses to intravenous sodium lactate challenge or
      single-breath inhalation of 35% carbon dioxide versus a similar breath inhalation
      of clean air have shown a greater frequency of panic responses in subjects with
      IEI than in control subjects, although such responses did not occur in all
      subjects. Preliminary genetic findings suggest an increased frequency of a common
      genotype with panic disorder patients. The panic responses in a significant
      proportion of IEI patients opens a therapeutic window of opportunity. Patients in
      whom panic responses may at least be a contributing factor to their symptoms
      might be responsive to intervention with psychotherapy to enable their
      desensitization or deconditioning of responses to odors and other triggers,
      and/or may be helped by anxiolytic medications, relaxation training, and
      counseling for stress management.

PMID- 12194903
TI  - Indoor environmental exposures and symptoms.
AB  - The label "sick building syndrome" is often used to imply the absence of a
      physiologic basis for symptoms in the built environment. Although building
      related illness is widely recognized but considered rare, several well-studied
      mechanisms may be responsible for many symptoms in buildings. These mechanisms do
      not explain why some individuals perceive disability. Until researchers
      distinguish physiologic mechanisms from other aspects of disease and study them
      systematically, poorly defined symptoms will remain poorly understood. The
      disability associated with such symptoms and syndromes, not the physiology, is
      the primary interest and generates controversy.

PMID- 12194906
TI  - Role of arthropod saliva in blood feeding: sialome and post-sialome perspectives.
AB  - This review addresses the problems insects and ticks face to feed on blood and
      the solutions these invertebrates engender to overcome these obstacles, including
      a sophisticated salivary cocktail of potent pharmacologic compounds. Recent
      advances in transcriptome and proteome research allow an unprecedented insight
      into the complexity of these compounds, indicating that their molecular diversity
      as well as the diversity of their targets is still larger than previously
      thought.

PMID- 12194907
TI  - Surface membranes, Golgi complexes, and vacuolar systems.
AB  - In the absence of fossils, the cells of vertebrates are often described in lieu
      of a general animal eukaryote model, neglecting work on insects. However, a
      common ancestor is nearly a billion years in the past, making some vertebrate
      generalizations inappropriate for insects. For example, insect cells are adept at
      the cell remodeling needed for molting and metamorphosis, they have plasma
      membrane reticular systems and vacuolar ferritin, and their Golgi complexes
      continue to work during mitosis. This review stresses the ways that insect cells
      differ from those of vertebrates, summarizing the structure of surface membranes
      and vacuolar systems, especially of the epidermis and fat body, as a prerequisite
      for the molecular studies needed to understand cell function. The objective is to
      provide a structural base from which molecular biology can emerge from
      biochemical description into a useful analysis of function.

PMID- 12194905
TI  - A status report on chronic fatigue syndrome.
AB  - Medical history has shown that clinical disease entities or syndromes are
      composed of many subgroups--each with its own cause and pathogenesis. Although we
      cannot be sure, we expect the same outcome for chronic fatigue syndrome (CFS), a
      medically unexplained condition characterized by disabling fatigue accompanied by
      infectious, rheumatological, and neuropsychiatric symptoms. Although the ailment
      clearly can occur after severe infection, no convincing data exist to support an
      infectious (or immunologic) process in disease maintenance. Instead, data point
      to several possible pathophysiological processes: a covert encephalopathy,
      impaired physiological capability to respond to physical and mental stressors,
      and psychological factors related to concerns about effort exacerbating symptoms.
      Each of these is under intense investigation. In addition, some data do exist to
      indicate that environmental agents also can elicit a state of chronic fatigue. We
      expect data to accumulate to support the belief that CFS has multiple causes.

PMID- 12194908
TI  - Key interactions between neurons and glial cells during neural development in
      insects.
AB  - Nervous system function is entirely dependent on the intricate and precise
      pattern of connections made by individual neurons. Much of the insightful
      research into mechanisms underlying the development of this pattern of
      connections has been done in insect nervous systems. Studies of developmental
      mechanisms have revealed critical interactions between neurons and glia, the non
      neuronal cells of the nervous system. Glial cells provide trophic support for
      neurons, act as struts for migrating neurons and growing axons, form boundaries
      that restrict neuritic growth, and have reciprocal interactions with neurons that
      govern specification of cell fate and axonal pathfinding. The molecular
      mechanisms underlying these interactions are beginning to be understood. Because
      many of the cellular and molecular mechanisms underlying neural development
      appear to be common across disparate insect species, and even between insects and
      vertebrates, studies in developing insect nervous systems are elucidating
      mechanisms likely to be of broad significance.

PMID- 12194909
TI  - Tomato, pests, parasitoids, and predators: tritrophic interactions involving the
      genus Lycopersicon.
AB  - Insect-plant interactions involving the cultivated tomato and its relatives in
      the genus Lycopersicon have been intensively studied for several decades,
      resulting in one of the best documented and in-depth examples of the mechanistic
      complexities of insect-plant interactions, which encompass both herbivores and
      their natural enemies. Trichome-mediated defenses are particularly significant in
      L. hirsutum f. glabratum and have been extensively implicated in negative
      tritrophic effects mediated by direct contact of parasitoids and predators with
      trichomes, as well as indirect effects mediated through their hosts or prey. Both
      constitutive and inducible defense traits of L. esculentum exert effects on
      selected parasitoids and predators. The effects of any particular plant defense
      trait on parasitoids and predators depend on the specific attributes of the plant
      trait and the details of the physical, biochemical, and behavioral interaction
      between the natural enemy, its host (prey), and the plant.

PMID- 12194910
TI  - New markers for kidney disease.

PMID- 12194911
TI  - Genotyping of the common haptoglobin Hp 1/2 polymorphism based on PCR.
AB  - BACKGROUND: A genetically defined molecular heterogeneity of haptoglobin,
      characterized by the major phenotypic forms Hp 1-1, Hp 2-1, and Hp 2-2, has been
      associated with distinct clinical manifestations. To enable the use of DNA
      samples for the study of this polymorphism, we established a haptoglobin
      genotyping method based on PCR. METHODS: Taking advantage of the selectivity of
      PCR, we amplified DNA segments specifically representing haptoglobin alleles Hp 1
      and Hp 2 from genomic DNA. The products were analyzed by agarose gel
      electrophoresis. Haptoglobin phenotyping of plasma samples was performed by
      polyacrylamide gel electrophoresis and peroxidase staining. RESULTS: Exploiting
      the known size difference between Hp 1 and Hp 2, we amplified allele-specific DNA
      molecules with one pair of oligonucleotide primers. As an alternative, we used
      separate primer pairs to generate amplification products indicative of alleles Hp
      1 and Hp 2. Because of the primer design, genotype determination was not
      compromised by sequence variations specifying haptoglobin allele subtypes S and
      F. For the same reason, the sequence similarity between the haptoglobin gene and
      the haptoglobin-related gene did not interfere with the accuracy of genotyping.
      Analysis with restriction enzymes demonstrated the authenticity of the allele
      specific DNA products. Haptoglobin DNA genotyping and protein phenotyping,
      performed in parallel, yielded fully corresponding results. In a group of 249
      individuals, the haptoglobin genotype distribution was as follows: 14.5% Hp 1-1,
      48.2% Hp 2-1, and 37.3% Hp 2-2. CONCLUSION: The new method can be used for
      genotyping of a common haptoglobin polymorphism.

PMID- 12194912
TI  - Polymorphisms in the transcobalamin gene: association with plasma homocysteine in
      healthy individuals and vascular disease patients.
AB  - BACKGROUND: Hyperhomocysteinemia is an independent risk factor for cardiovascular
      disease (CVD). Intracellular vitamin B(12) deficiency may lead to increased
      plasma total homocysteine (tHcy) concentrations and because transcobalamin (TC)
      is the plasma transporter that delivers vitamin B(12) to cells, genetic variation
      in the TC gene may affect intracellular vitamin B(12) availability and,
      consequently, tHcy concentrations. METHODS: We examined five sequence variants,
      i.e., I23V, G94S, P259R, S348F, and R399Q, in the TC gene as possible
      determinants of tHcy and, concordantly, as possible risk factors for CVD in 190
      vascular disease patients and 601 controls. We also studied potential effect
      modification of vitamin B(12) by genotype. RESULTS: In individuals with high
      vitamin B(12), 259PP individuals had lower tHcy concentrations than 259PR and
      259RR individuals. Homozygous 23VV individuals had lower fasting tHcy
      concentrations than their 23IV and 23II peers. None of the genotypes defined by
      the three other sequence variants showed an association with tHcy concentrations,
      nor was any TC genotype associated with an increased CVD risk. CONCLUSIONS: In
      individuals in the highest quartile of the vitamin B(12) distribution (>299
      pmol/L), tHcy concentrations are lower in 259PP homozygotes than in 259PR and
      259RR individuals. Therefore, 259PP individuals, who represent >25% of the
      general population, may be more susceptible to reduction of plasma tHcy
      concentrations by increasing the vitamin B(12) status.

PMID- 12194913
TI  - Quantitative and compositional study of cardiolipin in platelets by electrospray
      ionization mass spectrometry: application for the identification of Barth
      syndrome patients.
AB  - BACKGROUND: The concentration of cardiolipin (CL) in cultured skin fibroblasts is
      a useful indicator of Barth syndrome (BTHS; MIM 302060), but the sampling and
      culturing of fibroblasts are burdensome and time-consuming procedures. We
      investigated whether the analysis of CL in platelets might help to identify BTHS
      in patients suspected of having this condition. METHODS: We used HPLC and online
      electrospray ionization mass spectrometry (HPLC-ESI-MS) to quantify CL molecular
      species. The CL content of platelets was studied in blood samples of BTHS and non
      BTHS patients. Control blood samples drawn from healthy adults were collected and
      analyzed within 24 h (n = 10) and 48 h (n = 10) to characterize any effect of
      sample shipping time on the CL content in platelets. Samples were collected from
      children 1-10 years of age who were not affected by BTHS (n = 6) and from BTHS
      patients (n = 4) and analyzed within 24 h. Results for all four groups were
      compared by a Student t-test for all individual analyses. RESULTS: We found
      different CL molecular species, e.g., (C18:2)(4)-CL. BTHS patients had a specific
      decrease of tetralinoleyl-CL concentrations in platelets (0.1-0.5 nmol/mg of
      protein; n = 4) compared with all control groups (2.3-5.5 nmol/mg of protein; n =
      26). Only minor differences were observed among the different control groups.
      CONCLUSIONS: Quantitative and compositional analyses of CL in platelets by the
      proposed method allow identification of BTHS patients more rapidly than gene
      analysis or analysis of CL in cultured skin fibroblasts. The abnormality of CL
      may explain the abnormal mitochondrial function observed in BTHS. The differences
      between the control groups did not cause any complication.

PMID- 12194914
TI  - Flow cytometric quantification of competitive reverse transcription-PCR products.
AB  - BACKGROUND: Competitive PCR of reverse transcribed mRNA sequences is used to
      quantify transcripts, but the usual approaches are labor-intensive and time
      consuming. We describe the non-gel-based quantification of competitive reverse
      transcription (RT)-PCR products with use of microparticles and flow cytometry.
      METHODS: PCR products of a target sequence and an internal control sequence
      (competitor) were labeled during PCR using digoxigenin (DIG)- and dinitrophenol
      (DNP)-labeled primer, respectively, allowing specific binding to microparticles
      coated with the corresponding antibody. Both amplification products were
      biotinylated to enable fluorescence labeling with streptavidin-R-phycoerythrin.
      The mean fluorescence intensity of each microparticle population, corresponding
      to the amount of bound PCR product, was measured in a flow cytometer. We
      constructed microparticles coated with antibodies against DIG and DNP to
      specifically capture PCR products derived from target and competitor sequences,
      respectively. RESULTS: As required for a reliable competitive PCR assay, nearly
      identical kinetics were found for the amplification of target and competitor
      sequences when using only one competitive primer. The method was applied to
      examine interleukin-8 expression in human lymphocytes after x-irradiation. One
      hour after irradiation, the concentration of transcripts decreased by half.
      CONCLUSIONS: The flow cytometric assay for the quantification of competitive RT
      PCR products avoids additional hybridization steps and antibody labeling. The use
      of paramagnetic microparticles would also enable the complete automation of this
      method.

PMID- 12194915
TI  - Determination of the factor V Leiden single-nucleotide polymorphism in a
      commercial clinical laboratory by use of NanoChip microelectronic array
      technology.
AB  - BACKGROUND: Methods for analysis of the single-nucleotide polymorphism (SNP)
      known as factor V Leiden (FVL) are described. The technique provides rapid,
      highly accurate detection of the point mutation that encodes for replacement of
      arginine-506 with glutamine. After formal assay qualification, 758 clinical
      samples that had previously been analyzed by the Invader Monoplex Assay were
      tested as research samples in a commercial clinical laboratory. METHODS: Primers
      specific for factor V (FV) were prepared, and PCR was performed. Samples were
      analyzed using the NanoChip Molecular Biology Workstation with fluorescently
      labeled reporters for wild-type and SNP sequences. RESULTS: Of the 635 samples
      classified by the Third Wave assay as FV wild type, 10 were identified as
      heterozygous FVL by the NanoChip technique. Similarly, of the 114 putative
      heterozygous samples, 4 were wild type, and of the 9 reported homozygous samples,
      6 were homozygous, 2 were heterozygous, and 1 was FV wild type by the NanoChip
      assay. All 17 results that were discordant with the Third Wave analysis were
      confirmed by DNA sequencing to be correctly classified by the NanoChip
      technology. The Nanochip system was 100% accurate in characterizing wild-type,
      heterozygous, and homozygous samples compared with accuracies of 99.2%, 90.2%,
      and 100% for the comparable Third Wave analysis. CONCLUSIONS: The NanoChip
      microelectronic chip array technology is an accurate and convenient method for
      FVL screening of research samples in a clinical laboratory environment.

PMID- 12194916
TI  - Rapid and reliable method for cytochrome P450 2D6 genotyping.
AB  - BACKGROUND: Single-nucleotide polymorphisms and single-base deletions within the
      cytochrome P450 2D6 (CYP2D6) gene have been associated with a poor metabolizer
      (PM) phenotype and display a frequency of 7-10% in the Caucasian population.
      METHODS: We developed a reliable and rapid procedure to identify five major PM
      associated mutations (CYP2D6*4, *7, and *8) and deletions (CYP2D6*3 and *6) by
      real-time PCR with subsequent fluorometric melting point analysis of the PCR
      product. These polymorphisms within the CYP2D6 gene were detected by use of two
      primer pairs and five different pairs of hybridization probes. DNA extracted from
      whole blood of 323 individuals was analyzed, and results were compared with
      genotypes obtained by allele-specific multiplex PCR. In case of uncertain
      results, additional sequence analysis was performed. RESULTS: Genotyping results
      by real-time PCR were 100% reliable, whereas conventional allele-specific
      multiplex PCR produced uncertain results for 12.1% of samples, as confirmed by
      sequence analysis. Costs for reagents and consumables were considerably higher
      for the real-time PCR technology, but labor time was reduced by 2 h compared with
      allele-specific PCR. The allele frequencies in the population investigated were
      0.186 for allele *4, 0.026 for allele *5, 0.009 for allele *3, 0.031 for allele
      *6, and 0.002 for allele *8. The defective CYP2D6*7 allele was not found. In
      addition, three additional mutations were detected, one of them displaying a PM
      genotype. CONCLUSION: Genotyping of CYP2D6 by real-time PCR with fluorometric
      melting point analysis is a rapid and reliable method.

PMID- 12194917
TI  - Predictive value of routine circulating soluble endothelial cell adhesion
      molecule measurements during pregnancy.
AB  - BACKGROUND: The present study was aimed at determining whether routine prenatal
      measurements of circulating soluble intercellular adhesion molecule (sICAM-1;
      CD54) and soluble vascular cell adhesion molecule (sVCAM-1; CD106) in
      midgestation have predictive value for the identification of pregnant women
      destined to develop preeclampsia or other complications of pregnancy during late
      gestation. METHODS: Plasma sICAM-1 and sVCAM-1 were analyzed between weeks 22 and
      29 of gestation in 1543 pregnant women and related to the outcome of pregnancy in
      a prospective longitudinal study. RESULTS: Plasma sICAM-1 and sVCAM-1 in
      uncomplicated pregnancies were normally distributed and varied over a small range
      (sICAM-1, SD = 22.5%; sVCAM-1, SD = 25.5%). Of all analyzed uncomplicated
      pregnancies, 54 (3.95%) were identified with concentrations of sICAM-1 or sVCAM-1
      above the mean + 2 SD. In contrast, of 177 pregnancies with complications
      (prevalence, 11.5%), 97 (55%) had sICAM-1 or sVCAM-1 concentrations above the
      same cutoffs weeks before the onset of disease. The sensitivities of sICAM-1 and
      sVCAM-1 measurements were 66% for preeclampsia and hemolysis, elevated liver
      enzymes, and low platelets (HELLP syndrome), 42% for gestational hypertension,
      50% for fetal retardation, 46% for preterm labor, 50% for gestational diabetes
      mellitus, 67% for gestational proteinuria, and 70% for infections during
      pregnancy. Taken together, routine prenatal sICAM-1 and sVCAM-1 measurements had
      an overall predictive value of 64%. CONCLUSIONS: Midgestation measurements of
      circulating sICAM-1 and sVCAM-1 have a high predictive value (area under the
      curve of combined sICAM-1 and sVCAM-1 measurements determined by ROC analysis,
      0.85) and may identify up to 55% of pregnant women who will later develop a
      severe pregnancy-related complication.

PMID- 12194918
TI  - Genetic covariation between serum gamma-glutamyltransferase activity and
      cardiovascular risk factors.
AB  - BACKGROUND: Several studies have shown that variation in serum gamma
      glutamyltransferase (GGT) in the population is associated with risk of death or
      development of cardiovascular disease, type 2 diabetes, stroke, or hypertension.
      This association is only partly explained by associations between GGT and
      recognized risk factors. Our aim was to estimate the relative importance of
      genetic and environmental sources of variation in GGT as well as genetic and
      environmental sources of covariation between GGT and other liver enzymes and
      markers of cardiovascular risk in adult twin pairs. METHODS: We recruited 1134
      men and 2241 women through the Australian Twin Registry. Data were collected
      through mailed questionnaires, telephone interviews, and by analysis of blood
      samples. Sources of variation in GGT, alanine aminotransferase (ALT), and
      aspartate aminotransferase (AST) and of covariation between GGT and
      cardiovascular risk factors were assessed by maximum-likelihood model-fitting.
      RESULTS: Serum GGT, ALT, and AST were affected by additive genetic and nonshared
      environmental factors, with heritabilities estimated at 0.52, 0.48, and 0.32,
      respectively. One-half of the genetic variance in GGT was shared with ALT, AST,
      or both. There were highly significant correlations between GGT and body mass
      index; serum lipids, lipoproteins, glucose, and insulin; and blood pressure.
      These correlations were more attributable to genes that affect both GGT and known
      cardiovascular risk factors than to environmental factors. CONCLUSIONS: Variation
      in serum enzymes that reflect liver function showed significant genetic effects,
      and there was evidence that both genetic and environmental factors that affect
      these enzymes can also affect cardiovascular risk.

PMID- 12194919
TI  - Single-point cardiac troponin T at coronary care unit discharge after myocardial
      infarction correlates with infarct size and ejection fraction.
AB  - BACKGROUND: One of the major concerns in replacing creatine kinase MB (CK-MB)
      with cardiac troponins is the lack of evidence of the ability of troponins to
      estimate the size of acute myocardial infarction (AMI). We investigated the
      ability of a single measurement of cardiac troponin T (cTnT) at coronary care
      unit (CCU) discharge to estimate infarct size and assess left ventricular (LV)
      function in AMI patients. METHODS: We studied 65 AMI patients in whom infarct
      size was estimated by CK-MB peak concentrations and gated single-photon emission
      computed tomography (SPECT) myocardial perfusion using technetium-99m sestamibi
      and LV function by SPECT imaging. Measurements of cTnT and SPECT were performed
      72 h (median) after admission (range, 40-160 h). SPECT was also repeated 3 months
      later. RESULTS: We found a significant correlation between cTnT and both the peak
      CK-MB concentrations (r = 0.76; P <0.001) and the perfusion defect size at SPECT
      (r = 0.62; P <0.001). cTnT was inversely related to LV ejection fraction (LVEF)
      assessed both early (r = -0.56; P <0.001) and 3 months after AMI (r = -0.70; P
      <0.001). cTnT >2.98 micro g/L predicted a LVEF <40% at 3 months with a
      sensitivity of 86.7%, specificity of 81.4%, and a likelihood ratio for a positive
      test of 4.7 (95% confidence interval, 4.0-5.4). CONCLUSIONS: A single cTnT
      measurement at CCU discharge after AMI is useful as a noninvasive estimate of
      infarct size and for the assessment of LV function in routine clinical setting.

PMID- 12194920
TI  - Serum reference intervals and diagnostic ranges for free kappa and free lambda
      immunoglobulin light chains: relative sensitivity for detection of monoclonal
      light chains.
AB  - BACKGROUND: The detection of monoclonal free light chains (FLCs) is an important
      diagnostic aid for a variety of monoclonal gammopathies and is especially
      important in light-chain diseases, such as light-chain myeloma, primary systemic
      amyloidosis, and light-chain-deposition disease. These diseases are more
      prevalent in the elderly, and assays to detect and quantify abnormal amounts of
      FLCs require reference intervals that include elderly donors. METHODS: We used an
      automated immunoassay for FLCs and sera from a population 21-90 years of age. We
      used the calculated reference and diagnostic intervals to compare FLC results
      with those obtained by immunofixation (IFE) to detect low concentrations of
      monoclonal kappa and lambda FLCs in the sera of patients with monoclonal
      gammopathies. RESULTS: Serum kappa and lambda FLCs increased with population age,
      with an apparent change for those >80 years. This trend was lost when the FLC
      concentration was normalized to cystatin C concentration. The ratio of kappa FLC
      to lambda FLC (FLC K/L) did not exhibit an age-dependent trend. The diagnostic
      interval for FLC K/L was 0.26-1.65. The 95% reference interval for kappa FLC was
      3.3-19.4 mg/L, and that for lambda FLC was 5.7-26.3 mg/L. Detection and
      quantification of monoclonal FLCs by nephelometry were more sensitive than IFE in
      serum samples from patients with primary systemic amyloidosis and light-chain
      deposition disease. CONCLUSIONS: Reference and diagnostic intervals for serum
      FLCs have been developed for use with a new, automated immunoassay that makes the
      detection and quantification of monoclonal FLCs easier and more sensitive than
      with current methods. The serum FLC assay complements IFE and allows
      quantification of FLCs in light-chain-disease patients who have no detectable
      serum or urine M-spike.

PMID- 12194921
TI  - Development and evaluation of a practical ELISA for human urinary lipocalin-type
      prostaglandin D synthase.
AB  - BACKGROUND: Urinary excretion of lipocalin-type prostaglandin D synthase (L-PGDS)
      is significantly increased in patients with chronic renal failure, but its
      diagnostic potential in less advanced stages of renal diseases remains to be
      elucidated. METHODS: Six mouse monoclonal antibodies (MAbs) were raised against
      recombinant human L-PGDS. We constructed a sandwich ELISA with two MAbs that
      recognized different epitopes with high affinities and assessed its assay
      performance and clinical utility with urine samples from healthy controls,
      diabetic patients, and patients with various renal diseases. RESULTS: Western
      blot analyses with NH(2)-terminus-truncated L-PGDS mapped the epitopes to Ala(23)
      Val(28) (MAb-7F5 and -10A3), Ser(52)-Ala(73) (MAb-9A6), Tyr(107)-Val(120) (MAb
      1B7 and -6F5), and Gly(140)-Pro(155) (MAb-6B9). A sandwich ELISA was constructed
      with MAb-1B7 and -7F5, the K(d) values of which were 3.6 and 3.9 nmol/L,
      respectively, for native L-PGDS. Recoveries were 91-111%, and intra- and
      interassay CVs were <6% and <9%, respectively. The ELISA showed parallelism of
      standard and urine samples and no significant interference by a variety of
      urinary constituents. Urinary L-PGDS excretion was significantly increased in
      patients with diabetic nephropathy, IgA nephropathy, and chronic
      glomerulonephritis even when serum creatinine was not increased. In patients with
      renal diseases, urinary L-PGDS was correlated with urinary albumin (r = 0.64; P
      <0.0001), N-acetyl-beta-D-glucosaminidase (r = 0.43; P <0.001), and serum
      creatinine (r = 0.66; P <0.0001). At a cutoff value of 284 mg/mol creatinine, the
      assay had sensitivities of 74% for diabetic nephropathy and 83% for chronic
      glomerulonephritis and a specificity of 93%. CONCLUSIONS: This ELISA system is
      suitable for measurement of urinary L-PGDS in a routine clinical assay and may be
      useful to detect less advanced stages of renal diseases.

PMID- 12194922
TI  - Effect of aspirin treatment on serum concentrations of lipoprotein(a) in patients
      with atherosclerotic diseases.
AB  - BACKGROUND: Increased serum lipoprotein(a) [Lp(a)] is an independent risk factor
      for atherosclerosis. We previously reported that aspirin reduced Lp(a) production
      by cultured hepatocytes via the reduction of apolipoprotein(a) [apo(a)] gene
      transcription. METHODS: We evaluated both the effect of aspirin treatment (81
      mg/day) on serum Lp(a) concentrations and the correlation between the degree of
      reduction in serum Lp(a) and the type of apo(a) isoform in 70 patients with
      coronary artery disease or cerebral infarction. RESULTS: Aspirin lowered serum
      Lp(a) concentrations to approximately 80% of the baseline values in patients with
      high Lp(a) concentrations (>300 mg/L). The percentage of decrease in serum Lp(a)
      was larger in patients with high Lp(a) than in patients with low Lp(a) (<300
      mg/L), irrespective of apo(a) isoform size. The decreases in serum Lp(a) in high
      Lp(a) patients with both the high-molecular-weight and the low-molecular-weight
      isoforms were positively correlated with the baseline Lp(a) concentrations.
      CONCLUSIONS: Because the secretory efficiencies of apo(a) in the same isoform are
      likely to be similar, the difference in serum Lp(a) concentrations in patients
      having the same apo(a) isoform depends on the transcriptional activity of the
      apo(a) gene. These findings suggest that aspirin decreases serum Lp(a)
      concentrations via a decrease in apo(a) gene transcription more effectively in
      patients with high transcriptional activity of this gene.

PMID- 12194924
TI  - Drug testing in blood: validated negative-ion chemical ionization gas
      chromatographic-mass spectrometric assay for determination of amphetamine and
      methamphetamine enantiomers and its application to toxicology cases.
AB  - BACKGROUND: Enantioselective analysis of amphetamine (AM) or methamphetamine (MA)
      in urine is already a well-established tool for differentiation of illicit from
      therapeutic ingestion of AM or MA derivatives. However, because of the increasing
      importance of plasma or serum in analytical toxicology, a method for
      enantioselective analysis of AM and MA in these matrices is needed. METHODS: AM
      and/or MA were extracted from 0.2 mL of blood plasma or serum by mixed-mode solid
      phase extraction. After derivatization with S-(-)-heptafluorobutyrylprolyl
      chloride, the resulting diastereomers were separated by gas chromatography on a
      HP-5MS column during a 15-min program and detected by mass spectrometry in the
      negative-ion chemical ionization mode (NICI-GC-MS). The method was fully
      validated and applied to >50 samples from authentic toxicology cases. RESULTS:
      The derivatized AM and MA enantiomers were well separated and sensitively
      detected. The method was linear from 5 to 250 micro g/L per enantiomer with
      analytical recoveries, accuracy, and within- and between-run precision well
      within required limits. Extraction yields were 88.9-98.6%. Implications of
      concentrations and enantiomeric composition of AM and MA in the authentic samples
      were considered. CONCLUSIONS: This sensitive, reliable, rapid NICI-GC-MS assay is
      suitable for enantioselective determination of AM and MA in blood plasma or serum
      samples.

PMID- 12194923
TI  - Simultaneous analysis of nicotine, nicotine metabolites, and tobacco alkaloids in
      serum or urine by tandem mass spectrometry, with clinically relevant metabolic
      profiles.
AB  - BACKGROUND: Assessment of nicotine metabolism and disposition has become an
      integral part of nicotine dependency treatment programs. Serum nicotine
      concentrations or urine cotinine concentrations can be used to guide nicotine
      patch dose to achieve biological concentrations adequate to provide the patient
      with immediate relief from nicotine withdrawal symptoms, an important factor in
      nicotine withdrawal success. Absence of nicotine metabolites and anabasine can be
      used to document abstinence from tobacco products, an indicator of treatment
      success. METHODS: The procedure was designed to quantify nicotine, cotinine,
      trans-3'-hydroxycotinine, anabasine, and nornicotine in human serum or urine. The
      technique required simple extraction of the sample with quantification by HPLC
      tandem mass spectrometry. RESULTS: The procedure for simultaneous analysis of
      nicotine, its metabolites, and tobacco alkaloids simultaneously quantified five
      different analytes. Test limit of quantification, linearity, imprecision, and
      accuracy were adequate for clinical evaluation of patients undergoing treatment
      for tobacco dependency. The test readily distinguished individuals who had no
      exposure to tobacco products from individuals who were either passively exposed
      or were abstinent past-tobacco users from those who were actively using a tobacco
      or nicotine product. CONCLUSIONS: Nicotine, cotinine, trans-3'-hydroxycotinine,
      nornicotine, and anabasine can be simultaneously and accurately quantified in
      either serum or urine by HPLC-tandem mass spectrometry with imprecision <10% at
      physiologic concentrations and limits of quantification ranging from 0.5 to 5
      micro g/L. Knowledge of serum or urine concentrations of these analytes can be
      used to guide nicotine replacement therapy or to assess tobacco abstinence in
      nicotine dependency treatment. These measurements are now an integral part of the
      clinical treatment and management of patients who wish to overcome tobacco
      dependence.

PMID- 12194925
TI  - Plasma and oral fluid pharmacokinetics and pharmacodynamics after oral codeine
      administration.
AB  - BACKGROUND: The ease, noninvasiveness, and safety of oral fluid collection have
      increased the use of this alternative matrix for drugs-of-abuse testing; however,
      few controlled drug administration data are available to aid in the
      interpretation of oral fluid results. METHODS: Single oral codeine doses (60 and
      120 mg/70 kg) were administered to 19 volunteers. Oral fluid and plasma were
      analyzed for free codeine, norcodeine, morphine, and normorphine by solid-phase
      extraction combined with gas chromatography-mass spectrometry (SPE/GC-MS).
      Physiologic and subjective effects were examined. RESULTS: Mean (SE) peak codeine
      concentrations were 214.2 +/- 27.6 and 474.3 +/- 77.0 micro g/L in plasma and
      638.4 +/- 64.4 and 1599.3 +/- 241.0 micro g/L in oral fluid. The oral fluid-to
      plasma ratio for codeine was relatively constant ( approximately 4) from 1 to 12
      h. The mean half-life (t(1/2)) of codeine was 2.2 +/- 0.10 h in plasma and 2.2 +/
      0.16 h in oral fluid. Significant dose-related miosis and increases in sedation,
      psychotomimetic effect, and "high" occurred after the high dose. Mean codeine
      oral fluid detection time was 21 h with a 2.5 microg/L cutoff, longer than that
      of plasma (12-16 h). Detection times with the proposed Substance Abuse and Mental
      Health Services Administration cutoff (40 microg/L) were only 7 h. Norcodeine,
      but not morphine or normorphine, was quantified in both plasma and oral fluid.
      CONCLUSIONS: The disposition of codeine over time was similar in plasma and oral
      fluid, but because of high variability, oral fluid codeine concentrations did not
      reliably predict concurrent plasma concentrations. Oral fluid testing is a useful
      alternative matrix for monitoring codeine exposure with a detection window of 7
      21 h for single doses, depending on cutoff concentrations. These controlled drug
      administration data should aid in the interpretation of oral fluid codeine
      results.

PMID- 12194926
TI  - Limited sampling strategy for the estimation of mycophenolic acid area under the
      curve in adult renal transplant patients treated with concomitant tacrolimus.
AB  - BACKGROUND: Significant relationships between the mycophenolic acid (MPA) area
      under the concentration-time curve (AUC(0-12h)) and the risks for acute rejection
      and side effects have been reported. We developed a practical method for
      estimation of MPA AUCs. Regression equations were developed using repeated cross
      validation for randomly chosen subsets, characterized statistically, and verified
      for acceptable performance. METHODS: Twenty-one renal transplant patients
      receiving 0.5 or 1.0 g of mycophenolate mofetil twice daily and concomitant
      tacrolimus provided a total of 50 pharmacokinetic profiles. MPA concentrations
      were measured by a validated HPLC method in 12 plasma samples collected at
      predose and at 30 and 60 min; 2, 3, 4, 6, 8, 9, 10, 11, and 12 h; 1 and 2 weeks;
      and 3 months after transplantation. Twenty-six 1-, 2-, or 3-sample estimation
      models were fit (r(2) = 0.341-0.862) to a randomly selected subset of the
      profiles using linear regression and were used to estimate AUC(0-12h) for the
      profiles not included in the regression fit, comparing those estimates with the
      corresponding AUC(0-12h) values, calculated with the linear trapezoidal rule,
      including all 12 timed MPA concentrations. The 3-sample models were constrained
      to include no samples past 2 h. RESULTS: The model using c(0h), c(0.5h), and
      c(2h) was superior to all other models tested (r(2) = 0.862), minimizing
      prediction error for the AUC(0-12h) values not included in the fit (i.e., the
      cross-validation error). The regression equation for AUC estimation that gave the
      best performance for this model was: 7.75 + 6.49c(0h) + 0.76c(0.5h) + 2.43c(2h).
      When we applied this model to the full data set, 41 of the 50 (82%) estimated AUC
      values were within 15% of the value of AUC(0-12h) calculated using all 12
      concentrations. CONCLUSIONS: This limited sampling strategy provides an effective
      approach for estimation of the full MPA AUC(0-12h) in renal transplant patients
      receiving concomitant tacrolimus therapy.

PMID- 12194927
TI  - Comparison of two provocative tests for calcitonin in medullary thyroid
      carcinoma: omeprazole vs pentagastrin.
AB  - BACKGROUND: Provocative tests for calcitonin (CT) are fundamental in the
      diagnosis and follow-up of C-cell disease and in the detection of hereditary
      medullary thyroid carcinoma (MTC) carriers with unknown RET mutations. A recent
      report has proposed omeprazole, which can increase endogenous gastrin (GT), as a
      new provocative test for MTC. METHODS: We compared the omeprazole test (20 mg
      twice a day for 4 days) to the pentagastrin test (0.5 microg/kg of body weight)
      for the diagnosis and management of MTC. Twenty healthy individuals and 20 MTC
      patients with mildly or moderately increased basal CT serum concentrations
      underwent the pentagastrin and omeprazole tests. RESULTS: In MTC patients, the
      pentagastrin test produced a significantly higher increase in serum CT than did
      omeprazole. After the pentagastrin injection, several patients reported
      unpleasant side effects, including substantial tightness in 38 of 40
      participants. No adverse effects were observed during the omeprazole test. A
      significant direct correlation was recorded between CT% (ratio of CT peak to
      basal value x 100) and GT% (ratio of GT peak to basal value x 100) during the
      omeprazole test in MTC patients (r = 0.73; P <0.001). CONCLUSIONS: In spite of
      several adverse effects, pentagastrin remains the best provocative test for the
      diagnosis of MTC. Omeprazole may be useful when pentagastrin is contraindicated
      or refused because of the unpleasant side effects, but further validation is
      needed.

PMID- 12194928
TI  - Validation of a high-throughput liquid chromatography-tandem mass spectrometry
      method for urinary cortisol and cortisone.
AB  - BACKGROUND: Urinary free cortisol and cortisone measurements are useful in
      evaluation of Cushing syndrome, apparent mineralocorticoid excess, congenital
      adrenal hyperplasia, and adrenal insufficiency. To reduce analytical
      interference, improve accuracy, and shorten the analysis time, we developed a
      liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for urinary
      cortisol and cortisone. METHODS: We added 190 pmol (70 ng) of stable isotope
      cortisol-9,11,12,12-d(4) to 0.5 mL of urine as an internal standard before
      extraction. The urine was extracted with 4.5 mL of methylene chloride, washed,
      and dried, and 10 microL of the reconstituted extract was injected onto a
      reversed-phase C(18) column and analyzed using a tandem mass spectrometer
      operating in the positive mode. RESULTS: Multiple calibration curves for urinary
      cortisol and cortisone exhibited consistent linearity and reproducibility in the
      range 7-828 nmol/L (0.25-30 microg/dL). Interassay CVs were 7.3-16% for mean
      concentrations of 6-726 nmol/L (0.2-26.3 microg/dL) for cortisol and cortisone.
      The detection limit was 6 nmol/L (0.2 microg/dL). Recovery of cortisol and
      cortisone added to urine was 97-123%. The regression equation for the LC-MS/MS
      (y) and HPLC (x) method for cortisol was: y = 1.11x + 0.03 microg cortisol/24 h
      (r(2) = 0.992; n = 99). The regression equation for the LC-MS/MS (y) and
      immunoassay (x) methods for cortisol was: y = 0.66x - 12.1 microg cortisol/24 h
      (r(2) = 0.67; n = 99). CONCLUSION: The sensitivity and specificity of the LC
      MS/MS method for urinary free cortisol and cortisone offer advantages over
      routine immunoassays or chromatographic methods because of elimination of drug
      interferences, high throughput, and short chromatographic run time.

PMID- 12194929
TI  - Commutability assessment of potential reference materials using a multicenter
      split-patient-sample between-field-methods (twin-study) design: study within the
      framework of the Dutch project "Calibration 2000".
AB  - BACKGROUND: The Dutch project "Calibration 2000" aims at harmonization of
      laboratory results via calibration by development of commutable, matrix-based,
      secondary reference materials. An alternative approach to the NCCLS EP14 protocol
      for studying commutability of reference materials is presented, the "twin-study
      design", which in essence is a multicenter, split-patient-sample, between-field
      methods protocol. METHODS: The study consisted of the simultaneous analysis of
      fresh patient sera and potential reference materials (PRMs) for HDL-cholesterol
      (HDL-C) by 86 laboratories forming 43 laboratory couples. Six subgroups of method
      combinations were formed. The patient sera were selected and interchanged by each
      laboratory couple. The PRMs consisted of three types: C37, prepared according to
      the NCCLS C37 protocol; Fro, frozen selectively pooled human serum; and Lyo,
      which was the same serum pool as Fro but lyophilized in the presence of sucrose.
      All PRMs were provided in three HDL-C concentrations. The regression line
      residuals for the PRMs were normalized by expressing them as multiples of the
      state-of-the-art within laboratory SD (SD(SA)). In addition, the extra
      contribution of each PRM to the total measurement uncertainty, CV(Netto), was
      calculated. RESULTS: Averaged over the three PRM concentrations, 1.6% of the C37
      residuals were outside the 3 SD(SA) limit. For the Fro and Lyo PRMs, these values
      were 2.4% and 11.1%. CV(Netto) values for C37, Fro, and Lyo were 2.9%, 4.3%, and
      5.3%, respectively. CONCLUSIONS: The present twin-study design, as a practical
      alternative to the NCCLS EP14 protocol, is a viable way of studying commutability
      characteristics of PRMs. The study suggests that the C37 PRMs are the best
      candidates for a future reference material.

PMID- 12194930
TI  - Selection, preparation, and characterization of commutable frozen human serum
      pools as potential secondary reference materials for lipid and apolipoprotein
      measurements: study within the framework of the Dutch project "Calibration 2000".
AB  - BACKGROUND: The Dutch project "Calibration 2000" aims at harmonization of
      laboratory results via calibration by development of matrix-based secondary
      reference materials. We considered the selection, preparation, and
      characterization of 34 potential reference materials (PRMs). METHODS: Sixteen
      PRMs were prepared either strictly according to the NCCLS C37-A protocol or in a
      less stringent and more convenient way. In addition, 18 commercial, so-called
      human serum-based calibrators or controls were purchased and tested. Lipoprotein
      integrity was evaluated by examining the physicochemical characteristics of the
      materials. Commutability of the PRMs was assessed in 86 Dutch clinical
      laboratories, using a multicenter split-patient-sample between-field-method (twin
      study) design. Normalized residuals of the PRMs with respect to the patient
      regression lines were calculated; in addition, the extra contribution of each PRM
      to the total measurement uncertainty (CV(Netto)) was calculated. On the basis of
      these results, the most native PRM was selected to investigate its potential to
      reduce interlaboratory variation and to improve lipid and apolipoprotein
      standardization. RESULTS: In general, only the NCCLS C37-A-type materials
      displayed normalized residuals below the decision limit for commutability and had
      small CV(Netto) values ranging between 0 and 3.8%. This contrasts with the
      findings in regularly pooled frozen sera and lyophilized cryoprotected PRMs. In
      two subsequent external quality assessment surveys, the NCCLS type C37-A
      materials contributed to reducing the intermethod lipid and (apo)lipoprotein
      variation to approximately 2-4%. CONCLUSIONS: NCCLS C37-A materials have a strong
      potential as secondary reference materials, not only for cholesterol but also for
      HDL-cholesterol, LDL-cholesterol, triglyceride, and apolipoprotein measurements.

PMID- 12194931
TI  - Interlaboratory variation of plasma total homocysteine measurements: results of
      three successive homocysteine proficiency testing surveys.
AB  - BACKGROUND: Numerous studies have demonstrated that increased plasma total
      homocysteine (tHcy), whether measured after fasting or after a methionine load,
      is associated with increased risk for cardiovascular and thromboembolic diseases.
      However, little information is available regarding interlaboratory variation of
      tHcy measurements, especially at the increased tHcy concentrations observed after
      loading. METHODS: We conducted three Homocysteine Proficiency Testing Surveys at
      6-month intervals. Sets of five plasma pools with endogenous tHcy concentrations
      ranging from 5 to 48 micromol/L were sent to participants. We received 11, 23,
      and 17 responses in the first, second, and third surveys, respectively. The
      following methods were used by participating laboratories: fluorescence
      polarization immunoassay (FPIA); HPLC with fluorescent detection (HPLC-FD),
      further subdivided by type of reduction/derivatization; HPLC with electrochemical
      detection (HPLC-ED); amino acid analyzer with ninhydrin detection; and liquid
      chromatography-electrospray tandem mass spectrometry (LC-MS/MS). RESULTS: In
      surveys 1 and 2, no notable differences among the mean tHcy values obtained by
      the different methods performed were observed. In survey 3, tHcy values obtained
      by the FPIA method were significantly lower (P <0.05) at increased tHcy
      concentrations (34 micromol/L) compared with values obtained by HPLC-FD
      regardless of reduction/derivatization agents used. Our laboratory confirmed the
      observation that tHcy values obtained by the FPIA method differed from those
      obtained by HPLC-FD at increased tHcy concentrations by reanalyzing each pool 10
      times by FPIA and HPLC-FD using tributylphosphine-ammonium 7-fluoro-2,1,3
      benzoxadiazole-4-sulfonate (P <0.001 for tHcy >19 micro mol/L). The mean among
      method variations in surveys 1, 2, and 3 were 19%, 12%, and 9.6%, respectively.
      When results of the three surveys were combined, the mean among-method variation
      on 170 samples was 13%. Within-method variation was lowest for the FPIA method
      (4.4%), and ranged from 11-20% for HPLC methods. CONCLUSIONS: Various degrees of
      imprecision and lack of correlation among tHcy methods indicate that there is a
      need to improve analytical precision, decrease analytical difference, and
      standardize tHcy measurements among laboratories.

PMID- 12194932
TI  - Comparison of anti-transglutaminase ELISAs and an anti-endomysial antibody assay
      in the diagnosis of celiac disease: a prospective study.
AB  - BACKGROUND: Most studies of anti-transglutaminase (anti-tTG) assays have
      considered preselected groups of patients. This study compared the sensitivity,
      specificity, and predictive value of an immunofluorescence method for anti
      endomysial antibodies (EmAs) and two anti-tTG ELISAs, one using guinea pig tTG
      (gp-tTG) and the other human tTG (h-tTG) as antigen, in consecutive patients
      investigated for suspected celiac disease (CD). METHODS: We studied 207
      consecutive patients (99 men, 108 women; age range, 17-84 years) who underwent
      intestinal biopsy for suspected CD. Patients presented with one or more of the
      following: weight loss, anemia, chronic diarrhea, abdominal pain, dyspepsia,
      alternating bowel habits, constipation, pain in the joints, and dermatitis. At
      entry to the study, an intestinal biopsy was performed and a serum sample was
      taken for IgA EmAs, anti-gp-tTG, and anti-h-tTG. RESULTS: Intestinal histology
      showed that 24 patients had partial or total villous atrophy; in these patients
      the diagnosis of CD was confirmed by follow-up. The remaining 183 patients had
      villous/crypt ratios that were within our laboratory's reference values and were
      considered controls. Serum EmAs, anti-gp-tTG, and anti-h-tTG were positive in all
      24 CD patients; in the control group, none were positive for serum EmAs, but 15
      of 183 (8.2%) were positive for anti-gp-tTG, and 6 of 183 (3.3%) were positive
      for anti-h-tTG. Sensitivity was 100% for all assays, whereas specificity was 100%
      for the EmA, 92% for the anti-gp-tTG, and 97% for the anti-h-tTG assay. The
      negative predictive value was 100% for all assays; the positive predictive value
      was 100% for the EmA, 80% [95% confidence interval (CI), 65-95%] for the anti-h
      tTG (P = 0.03 vs EmA) and 60% (95% CI, 44-76%) for the anti-gp-tTG assay (P =
      0.0002 vs EmA). Areas (95% CIs) under the ROC curves were 0.987 (0.97-1.0) for
      anti-h-tTG and 0.965 (0.94-0.99) for anti-gp-tTG. Most of the patients testing
      false positive for anti-tTG had Crohn disease or chronic liver disease.
      CONCLUSIONS: Although both anti-tTG ELISAs showed optimum sensitivity, their lack
      of specificity yielded positive predictive values significantly lower than those
      for the EmA assay.

PMID- 12194934
TI  - Homogeneous, nonradioactive, enzymatic assay for plasma pyridoxal 5-phosphate.
AB  - BACKGROUND: Pyridoxal 5'-phosphate (PLP) is the biologically active form of
      vitamin B(6). Clinical studies suggest that low PLP concentrations are an
      independent risk factor for cardiovascular and other diseases. However, PLP
      concentrations are not routinely diagnosed because of the lack of a homogeneous,
      nonradioactive assay. We describe a homogeneous, nonradioactive, enzymatic PLP
      assay that uses the apo form of the PLP-dependent recombinant enzyme,
      homocysteine-alpha,gamma-lyase (rHCYase). METHODS: PLP was removed from
      holoenzyme rHCYase by incubation with hydroxylamine to obtain apo-rHCYase. The
      restoration of enzymatic activity by reconstitution of the holoenzyme was
      linearly related to the amount of PLP bound to the enzyme. The amplification
      principle of the assay allowed nanomolar concentrations of PLP to be measured by
      the conversion (by reconstituted holo-rHCYase) of millimolar concentrations of
      homocysteine to H(2)S. N,N-Dibutylphenylenediamine (DBPDA) was used for
      determination of H(2)S, the combination of which forms a chromophore with high
      absorbance. The assay was initiated by incubation of 5 microL of plasma with apo
      rHCYase in a binding buffer for 60 min at 37 degrees C. Homocysteine (2.5 mmol/L)
      was added to the assay buffer and incubated at 37 degrees C for 20 min. The DBPDA
      reaction was allowed to progress for 10 min and then read at 675 nm. RESULTS: The
      PLP enzymatic assay has a lower limit of detection of 5 nmol/L and is linear to
      200 nmol/L. The recovery of PLP was 98%. The mean within- and between-run CVs
      were 9.6% and 12%, respectively. Correlation of 45 samples in the PLP enzymatic
      assay and the B(6) (3)H radioenzymatic assay (American Laboratory Products Co.,
      Ltd.) yielded: y = 0.9367x + 10.569 (R(2) = 0.9201). CONCLUSIONS: This new PLP
      assay is the first homogeneous, nonradioactive, vitamin B(6) diagnostic method.
      The assay is applicable to chemistry automated analyzers and may have wide
      clinical use.

PMID- 12194933
TI  - Quantitative analysis of p40/p46 and p69/p71 forms of 2',5'-oligoadenylate
      synthetase mRNA by competitive PCR and its clinical application.
AB  - BACKGROUND: 2',5'-Oligoadenylate synthetases (2-5AS) are type I interferon (IFN)
      induced proteins with antiviral capacity. Three major forms of 2-5AS with
      distinct enzymatic activities have been described in IFN-treated human cells. We
      measured distinct forms of 2-5AS mRNA to analyze the relationship with its
      enzymatic activity and response to IFN therapy in chronic hepatitis C. METHODS:
      We established a method to quantify p40/p46 and p69/p71 forms of 2-5AS mRNA by
      use of reverse transcription followed by competitive PCR. The 2-5AS mRNA
      concentrations were measured in peripheral blood mononuclear cells from 40
      patients with chronic hepatitis C and 28 control individuals. RESULTS:
      Reconstitution experiments and comparison with Northern blot analyses revealed
      that our method accurately and linearly quantified 2-5AS mRNA. 2-5AS mRNA
      concentrations and 2-5AS enzymatic activity were correlated (P <0.03). Our data
      demonstrated a correlation in 2-5AS mRNA between p40/p46 and p69/p71 (P <0.02),
      indicating a similar regulation of the expression of these genes. Our data also
      demonstrated that pretreatment concentrations of 2-5AS mRNA correlated with
      responses to IFN therapy in chronic hepatitis C. CONCLUSIONS: Our method for
      measuring 2-5AS mRNA concentrations could provide an important marker for
      selecting patients for IFN therapy and may be useful for the development of more
      effective therapeutic strategies for chronic hepatitis C.

PMID- 12194935
TI  - Modification of fully automated total iron-binding capacity (TIBC) assay in serum
      and comparison with dimension TIBC method.
AB  - BACKGROUND: We previously reported the development of a fully automated assay for
      total iron-binding capacity (TIBC) in serum, using a multipurpose automated
      analyzer. However, this method requires four different reagents and is thus
      useful only with a limited number of available analyzers. We simplified our
      original assay and compared the analytical performance of the modified method
      with that of a commercial, fully automated TIBC assay (Dimension TIBC assay).
      METHODS: We simplified our original method to require only three reagents.
      Calibration was also altered and was performed with human transferrin standard
      solutions. An advantage of this method is that it does not require separation of
      excess unbound iron after the first step of transferrin saturation. Unbound iron
      is eliminated by formation of a complex with the chromogenic reagent ferrozine in
      the second step. Iron dissociated from transferrin by acidic pH reacts with
      ferrozine to form a colored complex in the final step, and the increase in
      absorbance at 570/660 nm is directly proportional to the TIBC measured. TIBC
      values were determined for 49 healthy individuals and 148 patients with this
      modified TIBC assay and with a commercial, fully automated TIBC method (Dimension
      clinical chemistry system), and calculation of TIBC based on the sum of the serum
      iron and unsaturated iron-binding capacity was performed for 97 patients.
      RESULTS: The within-run CVs for the modified TIBC assay and the Dimension TIBC
      assay were <4.8% and <2.4%, and the between-run CVs were 1.2% and 1.7%,
      respectively. The dilution curves were linear for TIBC values up to at least 180
      micromol/L with both methods. TIBC values obtained by our method were linearly
      correlated with serum transferrin concentrations (r = 0.984; S(y/x) = 3.18
      micromol/L; P <0.001). The correlation between the values obtained with the
      present method (y) and those obtained with the Dimension TIBC method (x) was y =
      1.04x + 1.19 micromol/L (r = 0.985; S(y/x) = 2.47 micromol/L), and with the
      calculation method (x) was y = 1.18x + 2.62 micromol/L (r = 0.976; S(y/x) = 3.27
      micromol/L). CONCLUSIONS: Our modified, fully automated TIBC assay performed
      similarly to the Dimension TIBC assay and is adaptable for use with many
      multipurpose automated analyzers.

PMID- 12194937
TI  - Comparison of methods for the detection of oligoclonal IgG bands in cerebrospinal
      fluid and serum: results of the Dutch Quality Control survey.

PMID- 12194936
TI  - Riboflavin, flavin mononucleotide, and flavin adenine dinucleotide in human
      plasma and erythrocytes at baseline and after low-dose riboflavin
      supplementation.
AB  - BACKGROUND: Vitamin B(2) exists in blood as riboflavin and its cofactors, flavin
      mononucleotide (FMN) and FAD. The erythrocyte glutathione reductase activation
      coefficient (EGRAC) has traditionally been used to assess vitamin B(2) status in
      humans. We investigated the relationships of EGRAC and plasma and erythrocyte
      concentrations of riboflavin, FMN, and FAD in elderly volunteers and their
      responses to riboflavin administration. METHODS: EGRAC and plasma and erythrocyte
      concentrations of riboflavin, FMN, and FAD were determined in 124 healthy
      individuals with a mean age of 69 years. The same measurements were made in a
      subgroup of 46 individuals with EGRAC > or =1.20 who participated in a randomized
      double-blind 12-week intervention study and received riboflavin (1.6 mg/day; n =
      23) or placebo (n = 23). RESULTS: Median plasma concentrations were 10.5 nmol/L
      for riboflavin, 6.6 nmol/L for FMN, and 74 nmol/L for FAD. In erythrocytes, there
      were only trace amounts of riboflavin, whereas median FMN and FAD concentrations
      were 44 and 469 nmol/L, respectively. Erythrocyte FMN and FAD correlated with
      each other and with EGRAC and plasma riboflavin (P <0.05). All variables except
      plasma FAD responded significantly to riboflavin supplementation compared with
      placebo (P < or =0.04). The strongest increases were for riboflavin in plasma
      (83%) and for FMN in erythrocytes (87%). CONCLUSIONS: Concentrations of all B(2)
      vitamers except plasma FAD are potential indicators of vitamin B(2) status, and
      plasma riboflavin and erythrocyte FMN may be useful for the assessment of vitamin
      B(2) status in population studies.

PMID- 12194938
TI  - Comparable effects of DIGIBIND and DigiFab in thirteen digoxin immunoassays.

PMID- 12194939
TI  - Ultrasensitive semiautomated chemiluminescent immunoassay for estradiol.

PMID- 12194940
TI  - Iron-replete reference intervals to increase sensitivity of hematologic and iron
      status laboratory tests in the elderly.

PMID- 12194941
TI  - Analytical requirements for measuring monocytic human lymphocyte antigen DR by
      flow cytometry: application to the monitoring of patients with septic shock.

PMID- 12194942
TI  - Identification of major CYP2C9 and CYP2C19 polymorphisms by fluorescence
      resonance energy transfer analysis.

PMID- 12194943
TI  - Monitoring analytical quality in routine glycohemoglobin measurements.

PMID- 12194944
TI  - Newly identified apolipoprotein AV gene predisposes to high plasma triglycerides
      in familial combined hyperlipidemia.

PMID- 12194945
TI  - Detection of monoclonal proteins in sera by capillary zone electrophoresis and
      free light chain measurements.

PMID- 12194946
TI  - Primer-extension preamplified DNA is a reliable template for genotyping.

PMID- 12194947
TI  - Two assays for urinary N-acetyl-beta-D-glucosaminidase compared.

PMID- 12194948
TI  - Single-nucleotide polymorphism allele frequencies determined by quantitative
      kinetic assay of pooled DNA.

PMID- 12194949
TI  - Web-based competency assessment system for microscopic urinalysis.

PMID- 12194950
TI  - No influence of heparin plasma and other (pre)analytic variables on D-dimer
      determinations.

PMID- 12194951
TI  - Clinical evaluation of an automated nucleic acid isolation system.

PMID- 12194952
TI  - Short-term stability of lysergic acid diethylamide (LSD), N-desmethyl-LSD, and 2
      oxo-3-hydroxy-LSD in urine, assessed by liquid chromatography-tandem mass
      spectrometry.

PMID- 12194953
TI  - Fate of fetal nucleated erythrocytes circulating in maternal blood: apoptosis is
      induced by maternal oxygen concentration.

PMID- 12194954
TI  - Microchips: an all-language literature survey including books and patents.

PMID- 12194955
TI  - Evaluation and performance characteristics of the STA-R coagulation analyzer.

PMID- 12194956
TI  - Lot-to-lot inconsistency of anticardiolipin reagents.

PMID- 12194957
TI  - Characteristics of the cardiac troponin I assay on the Immulite 2000 analyzer.

PMID- 12194960
TI  - Automated DNA extraction for real-time PCR.

PMID- 12194959
TI  - Reliable measurement of glycated hemoglobin in frozen blood samples: implications
      for epidemiologic studies.

PMID- 12194961
TI  - Macrolide treatment does not influence serum homocysteine in Chlamydia pneumoniae
      seropositive patients suffering from atherosclerosis.

PMID- 12194965
TI  - Angiogenic oligosaccharides of hyaluronan induce multiple signaling pathways
      affecting vascular endothelial cell mitogenic and wound healing responses.
AB  - Hyaluronan (HA) is a large nonsulfated glycosaminoglycan and an important
      regulator of angiogenesis, in particular, the growth and migration of vascular
      endothelial cells. We have identified some of the key intermediates responsible
      for induction of mitogenesis and wound recovery. Treatment of bovine aortic
      endothelial cells with oligosaccharides of hyaluronan (o-HA) resulted in rapid
      tyrosine phosphorylation and plasma membrane translocation of phospholipase
      Cgamma1 (PLCgamma1). Cytoplasmic loading with inhibitory antibodies to PLCgamma1,
      Gbeta, and Galpha(i/o/t/z) inhibited activation of extracellular-regulated kinase
      1/2 (ERK1/2). Treatment with the Galpha(i/o) inhibitor, pertussis toxin, reduced
      o-HA-induced PLCgamma1 tyrosine phosphorylation, protein kinase C (PKC) alpha and
      beta1/2 membrane translocation, ERK1/2 activation, mitogenesis, and wound
      recovery, suggesting a mechanism for o-HA-induced angiogenesis through G
      proteins, PLCgamma1, and PKC. In particular, we demonstrated a possible role for
      PKCalpha in mitogenesis and PKCbeta1/2 in wound recovery. Using antisense
      oligonucleotides and the Ras farnesylation inhibitor FTI-277, we showed that o-HA
      induced bovine aortic endothelial cell proliferation, wound recovery, and ERK1/2
      activation were also partially dependent on Ras activation, and that o-HA
      stimulated tyrosine phosphorylation of the adapter protein Shc, as well as its
      association with Sos1. Binding of Src to Shc was required for its activation and
      for Ras-dependent activation of ERK1/2, cell proliferation, and wound recovery.
      Neither Src nor Ras activation was inhibited by pertussis toxin, suggesting that
      their activation was independent of heterotrimeric G-proteins. However, the
      specific Src kinase inhibitor PP2 inhibited Gbeta subunit co-precipitation with
      PLCgamma1, suggesting a possible role for Src in activation of PLCgamma1 and
      interaction between two distinct o-HA-induced signaling pathways.

PMID- 12194966
TI  - Galectins-3 and -7, but not galectin-1, play a role in re-epithelialization of
      wounds.
AB  - Disorders of wound healing characterized by impaired or delayed re
      epithelialization are a serious medical problem. These conditions affect many
      tissues, are painful, and are difficult to treat. In this study, using cornea as
      a model, we demonstrate for the first time the importance of carbohydrate-binding
      proteins galectins-3 and -7 in re-epithelialization of wounds. In two different
      models of corneal wound healing, re-epithelialization of wounds was significantly
      slower in galectin-3-deficient (gal3(-/-)) mice compared with wild-type
      (gal3(+/+)) mice. In contrast, there was no difference in corneal epithelial
      wound closure rates between galectin-1-deficient and wild-type mice. Quantitation
      of the bromodeoxyuridine-labeled cells in gal3(+/+) and gal3(-/-) corneas
      revealed that corneal epithelial cell proliferation rate is not perturbed in
      gal3(-/-) corneas. Exogenous galectin-3 accelerated re-epithelialization of
      wounds in gal3(+/+) mice but, surprisingly, not in the gal3(-/-) mice. Gene
      expression analysis using cDNA microarrays revealed that healing corneas of gal3(
      /-) mice contain markedly reduced levels of galectin-7 compared with those of
      gal3(+/+) mice. More importantly, unlike galectin-3, galectin-7 accelerated re
      epithelialization of wounds in both gal3(-/-) and gal3(+/+) mice. In
      corresponding experiments, recombinant galectin-1 did not stimulate the corneal
      epithelial wound closure rate. The extent of acceleration of re-epithelialization
      of wounds with both galectin-3 and galectin-7 was greater than that observed in
      most of the published studies using growth factors. These findings have broad
      implications for developing novel therapeutic strategies for treating nonhealing
      wounds.

PMID- 12194967
TI  - Di-Ras, a distinct subgroup of ras family GTPases with unique biochemical
      properties.
AB  - The small GTPase Ras family regulates a variety of cell functions including
      proliferation and differentiation. Here we have identified novel Ras members,
      human Di-Ras1 and Di-Ras2, belonging to a distinct branch of the GTPase family.
      Di-Ras1 and Di-Ras2 specifically expressed in heart and brain share 30-40%
      overall identity with other members of Ras family, however, they have the
      following characteristic substitutions at highly conserved regions among the Ras
      family. 1) Thr-63 and Ser-65 in Di-Ras are substituted for Ala-59 and Gln-61
      positions in Ha-Ras, respectively, that are known to be critical for GTP
      hydrolysis. 2) Within the effector domains, Di-Ras has Ile at a position
      corresponding to Asp-33 in Ha-Ras, which is important for its interaction with
      the downstream effector Raf. As predicted by these substitutions, Di-Ras has only
      a quite low level of GTPase activity and exists predominantly as a GTP-bound form
      upon its expression in living cells. Moreover, Di-Ras fails to interact with the
      Ras-binding domain of Raf, resulting in no stimulation of mitogen-activated
      protein kinase. Interestingly, introduction of Di-Ras into HEK293T cells induces
      large cellular vacuolation. These findings raise the possibility that Di-Ras
      might regulate cell morphogenesis in a manner distinct from other members of Ras
      family.

PMID- 12194968
TI  - Trimerization of the amino propeptide of type IIA procollagen using a 14-amino
      acid sequence derived from the coiled-coil neck domain of surfactant protein D.
AB  - The folding of a collagen triple helix usually requires the presence of
      additional sequences that contribute to the association and correct alignment of
      the collagen chains. We recently reported that the C-terminal neck and lectin
      domains of a collagenous C-type lectin, rat pulmonary surfactant protein D (SP
      D), are sufficient to drive the trimerization of a heterologous type IIA
      procollagen amino propeptide sequence. However, the conformation of the resulting
      trimeric IIA propeptide and the specific contributions of the SP-D sequence to
      trimerization were not elucidated. In the present study, we show that
      trimerization of the fusion protein is associated with correct folding of the
      collagen helix within the IIA propeptide domain (as assessed by circular
      dichroism) and that the constituent chains are hydroxylated. Chemical cross
      linking and analytical ultracentrifugation showed that the IIA amino-propeptide
      retains its trimeric configuration even after proteolytic removal of the SP-D
      domains. By contrast, IIA amino-propeptides synthesized without fusion to the
      neck or lectin domains are assembled exclusively as monomers. To localize the
      trimerization sequence, mutant chimeric cDNA constructs were designed containing
      premature termination codons within the coiled-coil neck domain. A short, 14
      amino acid sequence corresponding to the first two heptad repeats of the neck
      domain was sufficient to drive the trimeric association of the IIA amino
      propeptide alpha-chains. However, deletion of the collagen domain resulted in the
      secretion of monomers. These studies demonstrate that two heptad repeats are
      sufficient for trimeric association of the propeptide but indicate that
      cooperative interactions between the coiled-coil and collagen domains are
      required for the formation of a stable helix.

PMID- 12194969
TI  - Protein farnesyltransferase and protein prenylation in Plasmodium falciparum.
AB  - Comparison of the malaria parasite and mammalian protein prenyltransferases and
      their cellular substrates is important for establishing this enzyme as a target
      for developing antimalarial agents. Nineteen heptapeptides differing only in
      their carboxyl-terminal amino acid were tested as alternative substrates of
      partially purified Plasmodium falciparum protein farnesyltransferase. Only
      NRSCAIM and NRSCAIQ serve as substrates, with NRSCAIM being the best.
      Peptidomimetics, FTI-276 and GGTI-287, inhibit the transferase with IC(50) values
      of 1 and 32 nm, respectively. Incubation of P. falciparum-infected erythrocytes
      with [(3)H]farnesol labels 50- and 22-28-kDa proteins, whereas
      [(3)H]geranylgeraniol labels only 22-28-kDa proteins. The 50-kDa protein is shown
      to be farnesylated, whereas the 22-28-kDa proteins are geranylgeranylated,
      irrespective of the labeling prenol. Protein labeling is inhibited more than 50%
      by either 5 microm FTI-277 or GGTI-298. The same concentration of inhibitors also
      inhibits parasite growth from the ring stage by 50%, decreases expression of
      prenylated proteins as measured with prenyl-specific antibody, and inhibits
      parasite differentiation beyond the trophozoite stage. Furthermore,
      differentiation specific prenylation of P. falciparum proteins is demonstrated.
      Protein labeling is detected predominantly during the trophozoite to schizont and
      schizont to ring transitions. These results demonstrate unique properties of
      protein prenylation in P. falciparum: a limited specificity of the
      farnesyltransferase for peptide substrates compared with mammalian enzymes, the
      ability to use farnesol to label both farnesyl and geranylgeranyl moieties on
      proteins, differentiation specific protein prenylation, and the ability of
      peptidomimetic prenyltransferase inhibitors to block parasite differentiation.

PMID- 12194970
TI  - Reactive oxygen nitrogen species decrease cystic fibrosis transmembrane
      conductance regulator expression and cAMP-mediated Cl- secretion in airway
      epithelia.
AB  - We investigated putative mechanisms by which nitric oxide modulates cystic
      fibrosis transmembrane conductance regulator (CFTR) expression and function in
      epithelial cells. Immunoprecipitation followed by Western blotting, as well as
      immunocytochemical and cell surface biotinylation measurements, showed that
      incubation of both stably transduced (HeLa) and endogenous CFTR expressing
      (16HBE14o-, Calu-3, and mouse tracheal epithelial) cells with 100 microm
      diethylenetriamine NONOate (DETA NONOate) for 24-96 h decreased both
      intracellular and apical CFTR levels. Calu-3 and mouse tracheal epithelial cells,
      incubated with DETA NONOate but not with 100 microm 8-bromo-cGMP for 96 h,
      exhibited reduced cAMP-activated short circuit currents when mounted in Ussing
      chambers. Exposure of Calu-3 cells to nitric oxide donors resulted in the
      nitration of a number of proteins including CFTR. Nitration was augmented by
      proteasome inhibition, suggesting a role for the proteasome in the degradation of
      nitrated proteins. Our studies demonstrate that levels of nitric oxide that are
      likely to be encountered in the vicinity of airway cells during inflammation may
      nitrate CFTR resulting in enhanced degradation and decreased function. Decreased
      levels and function of normal CFTR may account for some of the cystic fibrosis
      like symptoms that occur in chronic inflammatory lung diseases associated with
      increased NO production.

PMID- 12194971
TI  - Induction of heme oxygenase 1 by nitrosative stress. A role for nitroxyl anion.
AB  - Nitric oxide and S-nitrosothiols modulate a variety of important physiological
      activities. In vascular cells, agents that release NO and donate nitrosonium
      cation (NO(+)), such as S-nitrosoglutathione, are potent inducers of the
      antioxidant protein heme oxygenase 1 (HO-1) (Foresti, R., Clark, J. E., Green, C.
      J., and Motterlini, R. (1997) J. Biol. Chem. 272, 18411-18417; Motterlini, R.,
      Foresti, R., Bassi, R., Calabrese, V., Clark, J. E., and Green, C. J. (2000) J.
      Biol. Chem. 275, 13613-13620). Here, we report that Angeli's salt (AS) (0.25-2
      mm), a compound that releases nitroxyl anion (NO(-)) at physiological pH, induces
      HO-1 mRNA and protein expression in a concentration- and time-dependent manner,
      resulting in increased heme oxygenase activity in rat H9c2 cells. A time course
      analysis revealed that NO(-)-mediated HO-1 expression is transient and gradually
      disappears within 24 h, in accordance with the short half-life of AS at 37
      degrees C (t(12) = 2.3 min). Interestingly, multiple additions of AS at lower
      concentrations (50 or 100 microm) over a period of time still promoted a
      significant increase in heme oxygenase activity. Experiments performed using a NO
      scavenger and the NO electrode confirmed that NO(-), not NO, is the species
      involved in HO-1 induction by AS; however, the effect on heme oxygenase activity
      can be amplified by accelerating the rate of NO(-) oxidation. N-Acetylcysteine
      almost completely abolished AS-mediated induction of HO-1, whereas a glutathione
      synthesis inhibitor (buthionine sulfoximine) significantly decreased heme
      oxygenase activation by AS, indicating that sulfydryl groups are crucial targets
      in the regulation of HO-1 expression by NO(-). We conclude that NO(-), in analogy
      with other reactive nitrogen species, is a potent inducer of heme oxygenase
      activity and HO-1 protein expression. These findings indicate that heme oxygenase
      can act both as a sensor to and target of redox-based mechanisms involving NO and
      extend our knowledge on the biological function of HO-1 in response to
      nitrosative stress.

PMID- 12194972
TI  - A newly established neuronal rho-0 cell line highly susceptible to oxidative
      stress accumulates iron and other metals. Relevance to the origin of metal ion
      deposits in brains with neurodegenerative disorders.
AB  - From human neuroblastoma-derived SILA cells we have established a rho-0 cell line
      that is deficient in both respiration and mitochondrial DNA. Lactate
      dehydrogenase activity, lactate production, and growth in the medium without
      glucose indicate that these cells shift from aerobic to anaerobic metabolism.
      Electron microscopic observations revealed abnormal mitochondria with unique
      cristae structures. Staining with MitoTracker dye showed that the mitochondrial
      transmembrane potential was reduced by 30-40% from the parent cell levels. These
      cells were markedly susceptible to H(2)O(2) and died apparently by a necrotic
      mechanism, a process blocked by deferoxamine in the parent cells but not rho-0
      cells. Analysis by inductively coupled plasma-mass spectrometry revealed an
      approximately 3-fold accumulation of iron in the rho-0 cells at confluence (n = 4
      6, three clones, *p < 0.05). Iron and four other metals were all elevated in the
      cells of one of the rho-0 clones and were similar to control levels in the
      control cybrid cells, which were replenished with normal mitochondrial DNA. Their
      sensitivity to H(2)O(2) was also similar to that of the parent cells. These
      results indicate that a newly established neuronal related rho-0 cell line is
      highly susceptible to active oxygen species and that these toxicity effects
      appear to be related to an accumulation of transition metals, which probably
      occurs through the respiratory impairment.

PMID- 12194974
TI  - Direct and indirect contributions of RNA secondary structure elements to the
      initiation of HIV-1 reverse transcription.
AB  - Initiation of human immunodeficiency virus type 1 (HIV-1) reverse transcription
      requires specific recognition between the viral RNA (vRNA), tRNA(3)(Lys), which
      acts as primer, and reverse transcriptase (RT). The specificity of this ternary
      complex is mediated by intricate interactions between the HIV-1 RNA and
      tRNA(3)(Lys). Here, we compared the relative importance of the secondary
      structure elements of this complex in the initiation process. To this aim, we
      used the previously published three-dimensional model of the initiation complex
      to rationally introduce a series of deletions and substitutions in the vRNA. When
      necessary, we used chemical probing to check the structure of the tRNA(3)(Lys)
      mutant vRNA complexes. For each of them, we measured the binding affinity of RT
      and the kinetics of initial extension of tRNA(3)(Lys) and of synthesis of the (-)
      strand strong stop DNA. Our results were overall in keeping with the three
      dimensional model of the initiation complex. Surprisingly, we found that
      disruption of the intermolecular template-primer interactions, which are not
      directly recognized by RT, more severely affected reverse transcription than
      deletions or disruption of one of the intramolecular helices to which RT directly
      binds. Perturbations of the highly constrained junction between the
      intermolecular helix formed by the primer binding site and the 3' end of
      tRNA(3)(Lys) and the helix immediately upstream also had dramatic effects on the
      initiation of reverse transcription. Taken together, our results demonstrate the
      overwhelming importance of the overall three-dimensional structure of the
      initiation complex and identify structural elements that constitute promising
      targets for anti-initiation-specific drugs.

PMID- 12194975
TI  - The extracellular N-terminal domain and transmembrane domains 1 and 2 mediate
      oligomerization of a yeast G protein-coupled receptor.
AB  - G protein-coupled receptors (GPCRs) can form homodimers/oligomers and/or
      heterodimers/oligomers. The mechanisms used to form specific GPCR oligomers are
      poorly understood because the domains that mediate such interactions and the
      step(s) in the secretory pathway where oligomerization occurs have not been well
      characterized. Here we have used subcellular fractionation and fluorescence
      resonance energy transfer (FRET) experiments to show that oligomerization of a
      GPCR (alpha-factor receptor; STE2 gene product) of the yeast Saccharomyces
      cerevisiae occurs in the endoplasmic reticulum. To identify domains of this
      receptor that mediate oligomerization, we used FRET and endocytosis assays of
      oligomerization in vivo to analyze receptor deletion mutants. A mutant lacking
      the N-terminal extracellular domain and transmembrane (TM) domain 1 was expressed
      at the cell surface but did not self-associate. In contrast, a receptor fragment
      containing only the N-terminal extracellular domain and TM1 could self-associate
      and heterodimerize with wild type receptors. Analysis of other mutants suggested
      that oligomerization is facilitated by the N-terminal extracellular domain and
      TM2. Therefore, the N-terminal extracellular domain, TM1, and TM2 appear to
      stabilize alpha-factor receptor oligomers. These domains may form an interface in
      contact or domain-swapped oligomers. Similar domains may mediate dimerization of
      certain mammalian GPCRs.

PMID- 12194973
TI  - Inhibition of glucocorticoid-induced apoptosis in 697 pre-B lymphocytes by the
      mineralocorticoid receptor N-terminal domain.
AB  - The glucocorticoid and mineralocorticoid receptors (GR and MR) share considerable
      structural and functional homology and bind as homodimers to hormone-response
      elements. We have shown previously that MR and GR can form heterodimers that
      inhibit transcription from a glucocorticoid (GC)-responsive gene and that this
      inhibition was mediated by the N-terminal domain (NTD) of MR. In this report, we
      examined the effect of NTD-MR on GC-induced apoptosis in the GC-sensitive pre-B
      lymphoma cell line, 697. In GC-treated 697 cells, we demonstrated that stable
      expression of NTD-MR blocks apoptosis and inhibits proteolytic processing of pro
      caspases-3, -8, and -9 and poly(ADP-ribose) polymerase. Importantly, gel shift
      and immunoprecipitation analyses revealed a direct association between the GR and
      amino acids 203-603 of NTD-MR. We observed down-regulation of c-Myc and of the
      anti-apoptotic proteins Bcl-2 and Bfl-1 as well as high levels of the pro
      apoptotic proteins Bax and Bid. Conversely, cells stably expressing NTD-MR
      exhibited increased expression of Bcl-2 and Bfl-1 and diminished levels of Bid
      and Bax. These data provide a potential mechanism for the observed inhibition of
      cytochrome c and Smac release from the mitochondria of NTD-MR cells and resultant
      resistance to GC-induced apoptosis. Thus, NTD-MR may mediate GC effects through
      heterodimerization with GR and ensuing inhibition of GC-regulated gene
      transcription.

PMID- 12194978
TI  - The role of Grp 78 in alpha 2-macroglobulin-induced signal transduction. Evidence
      from RNA interference that the low density lipoprotein receptor-related protein
      is associated with, but not necessary for, GRP 78-mediated signal transduction.
AB  - The low density lipoprotein receptor-related protein (LRP) is a scavenger
      receptor that binds to many proteins, some of which trigger signal transduction.
      Receptor-recognized forms of alpha(2)-Macroglobulin (alpha(2)M*) bind to LRP, but
      the pattern of signal transduction differs significantly from that observed with
      other LRP ligands. For example, neither Ni(2+) nor the receptor-associated
      protein, which blocks binding of all known ligands to LRP, block alpha(2)M*
      induced signal transduction. In the current study, we employed alpha(2)
      macroglobulin (alpha(2)M)-agarose column chromatography to purify cell surface
      membrane binding proteins from 1-LN human prostate cancer cells and murine
      macrophages. The predominant binding protein purified from 1-LN prostate cancer
      cells was Grp 78 with small amounts of LRP, a fact that is consistent with our
      previous observations that there is little LRP present on the surface of these
      cells. The ratio of LRP:Grp 78 is much higher in macrophages. Flow cytometry was
      employed to demonstrate the presence of Grp 78 on the cell surface of 1-LN cells.
      Purified Grp 78 binds to alpha(2)M* with high affinity (K(d) approximately 150
      pm). A monoclonal antibody directed against Grp 78 both abolished alpha(2)M*
      induced signal transduction and co-precipitated LRP. Ligand blotting with
      alpha(2)M* showed binding to both Grp 78 and LRP heavy chains in these
      preparations. Use of RNA interference to silence LRP expression had no effect on
      alpha(2)M*-mediated signaling. We conclude that Grp 78 is essential for
      alpha(2)M*-induced signal transduction and that a "co-receptor" relationship
      exists with LRP like that seen with several other ligands and receptors such as
      the uPA/uPAR (urinary type plasminogen activator or urokinase/uPA receptor)
      system.

PMID- 12194976
TI  - Guinea pig phospholipase B, identification of the catalytic serine and the
      proregion involved in its processing and enzymatic activity.
AB  - Guinea pig phospholipase B (GPPLB) is a glycosylated ectoenzyme of intestinal
      brush border membrane. It displays a broad substrate specificity and is activated
      by trypsin cleavage. The primary sequence contains four tandem repeat domains (I
      to IV) and several serines in lipase consensus sequences. We used site-directed
      mutagenesis to demonstrate that only the serine 399 present in repeat II is
      responsible for the various enzymatic activities of GPPLB. Furthermore, we
      characterized for the first time the retinyl esterase activity of the enzyme. We
      also constructed and expressed in COS-7 cells, an NH(2)-terminal repeat I
      deletion mutant which was detected at a very low level by immunoblot. However,
      confocal microscopy study showed a strong intracellular accumulation with a weak
      membrane expression of the mutated protein, indicating a role of the NH(2)
      terminal repeat I in the processing of GPPLB. Nevertheless, the Western blot
      detected protein presented a glycosylation and trypsin sensitivity patterns
      similar to wild type PLB. The mutant is also fully active without trypsin
      treatment, in contrast to native enzyme. Thus, we propose a structural model for
      GPPLB, in which the repeat I constitutes a lid covering the active site and
      impairing enzymatic activity, its removal by trypsin leading to an active
      protein.

PMID- 12194977
TI  - Biochemical and functional characterization of human transmembrane tryptase
      (TMT)/tryptase gamma. TMT is an exocytosed mast cell protease that induces airway
      hyperresponsiveness in vivo via an interleukin-13/interleukin-4 receptor
      alpha/signal transducer and activator of transcription (STAT) 6-dependent
      pathway.
AB  - Transmembrane tryptase (TMT)/tryptase gamma is a membrane-bound serine protease
      stored in the secretory granules of human and mouse lung mast cells (MCs). We now
      show that TMT reaches the external face of the plasma membrane when MCs are
      induced to degranulate. Analysis of purified recombinant TMT revealed that it is
      a two-chain neutral protease. Thus, TMT is the only MC protease identified so far
      which retains its 18-residue propeptide when proteolytically activated. The genes
      that encode TMT and tryptase betaI reside on human chromosome 16p13.3. However,
      substrate specificity studies revealed that TMT and tryptase betaI are
      functionally distinct even though they are approximately 50% identical. Although
      TMT is rapidly inactivated by the human plasma serpin alpha(1)-antitrypsin in
      vitro, administration of recombinant TMT (but not recombinant tryptase betaI)
      into the trachea of mice leads to airway hyperresponsiveness (AHR) and increased
      expression of interleukin (IL) 13. T cells also increase their expression of IL
      13 mRNA when exposed to TMT in vitro. TMT is therefore a novel exocytosed surface
      mediator that can stimulate those cell types that are in close proximity. TMT
      induces AHR in normal mice but not in transgenic mice that lack signal transducer
      and activator of transcription (STAT) 6 or the alpha-chain of the cytokine
      receptor that recognizes both IL-4 and IL-13. Based on these data, we conclude
      that TMT is an exocytosed MC neutral protease that induces AHR in lungs primarily
      by activating an IL-13/IL-4Ralpha/STAT6-dependent pathway.

PMID- 12194979
TI  - Arrestin and its splice variant Arr1-370A (p44). Mechanism and biological role of
      their interaction with rhodopsin.
AB  - Deactivation of G-protein-coupled receptors relies on a timely blockade by
      arrestin. However, under dim light conditions, virtually all arrestin is in the
      rod inner segment, and the splice variant p(44) (Arr(1-370A)) is the stop protein
      responsible for receptor deactivation. Using size exclusion chromatography and
      biophysical assays for membrane-bound protein-protein interaction, membrane
      binding, and G-protein activation, we have investigated the interactions of Arr(1
      370A) and proteolytically truncated Arr(3-367) with rhodopsin. We find that these
      short arrestins do not only interact with the phosphorylated active receptor but
      also with inactive phosphorylated rhodopsin or opsin in membranes or solution.
      Because of the latter interaction they are not soluble (like arrestin) but
      membrane-bound in the dark. Upon photoexcitation, Arr(3-367) and Arr(1-370A)
      interact with prephosphorylated rhodopsin faster than arrestin and start to
      quench G(t) activation on a subsecond time scale. The data indicate that in the
      course of rhodopsin deactivation, Arr(1-370A) is handed over from inactive to
      active phosphorylated rhodopsin. This mechanism could provide a new aspect of
      receptor shutoff in the single photon operating range of the rod cell.

PMID- 12194980
TI  - The myostatin propeptide and the follistatin-related gene are inhibitory binding
      proteins of myostatin in normal serum.
AB  - Myostatin, also known as growth and differentiation factor 8, is a member of the
      transforming growth factor beta superfamily that negatively regulates skeletal
      muscle mass (1). Recent experiments have shown that myostatin activity is
      detected in serum by a reporter gene assay only after activation by acid,
      suggesting that native myostatin circulates as a latent complex (2). We have used
      a monoclonal myostatin antibody, JA16, to isolate the native myostatin complex
      from normal mouse and human serum. Analysis by mass spectrometry and Western blot
      shows that circulating myostatin is bound to at least two major proteins, the
      myostatin propeptide and the follistatin-related gene (FLRG). The myostatin
      propeptide is known to bind and inhibit myostatin in vitro (3). Here we show that
      this interaction is relevant in vivo, with a majority (>70%) of myostatin in
      serum bound to its propeptide. Studies with recombinant V5-His-tagged FLRG
      protein confirm a direct interaction between mature myostatin and FLRG.
      Functional studies show that FLRG inhibits myostatin activity in a reporter gene
      assay. These experiments suggest that the myostatin propeptide and FLRG are major
      negative regulators of myostatin in vivo.

PMID- 12194981
TI  - Functional role of arginine 373 in substrate translocation by the reduced folate
      carrier.
AB  - The reduced folate carrier (RFC) plays a critical role in the cellular uptake of
      folates. However, little is known regarding the mechanism used to transport
      substrates or the tertiary structure of the protein. Through the analysis of a
      Chinese hamster ovary cell line deficient in folate uptake, we have identified a
      single residue in TM10 (Arg-373) of RFC that appears to play a critical role in
      the translocation of substrate. Replacement of this position with various amino
      acids (KHQNA) diminished the rate of translocation by 16-50-fold, although
      substrate binding, protein stability, and localization were unaffected.
      Furthermore, the translocation capabilities of an R373C mutant in a cysteine-less
      form of the reduced folate carrier were enhanced 2.5-fold by the positively
      charged methanethiosulfonate reagent, confirming the essential role of a positive
      charge at this position. When considering the membrane-impermeable nature of this
      reagent, the data further suggest that the Arg-373 residue is located within the
      substrate translocation pathway of the RFC protein. Moreover, cross-linking
      analysis of the Arg-373 residue demonstrates that it is within 6 A of residue Glu
      394 (TM11), providing the first definitive tertiary structural information for
      this protein.

PMID- 12194982
TI  - Induction of Nod2 in myelomonocytic and intestinal epithelial cells via nuclear
      factor-kappa B activation.
AB  - Nod2, a member of the Apaf1/Nod protein family, confers responsiveness to
      bacterial products and activates NF-kappaB, a transcription factor that plays a
      central role in innate immunity. Recently, genetic variation in Nod2 has been
      associated with susceptibility to Crohn's disease. Here, we report that
      expression of Nod2 is induced upon differentiation of CD34(+) hematopoietic
      progenitor cells into granulocyte or monocyte/macrophages. In peripheral blood
      cells, the highest levels of Nod2 were observed in CD14(+) (monocytes), CD15(+)
      (granulocytes), and CD40(+)/CD86(+) (dendritic cells) cell populations. Notably,
      stimulation of myeloblastic and epithelial cells with bacterial
      lipopolysaccharide or TNFalpha resulted in up-regulation of Nod2. A search for
      consensus sites within the Nod2 promoter revealed a NF-kappaB binding element
      that was required for transcriptional activity in response to TNFalpha. Moreover,
      ectopic expression of p65 induced transactivation, whereas that of dominant
      negative IkappaBalpha blocked the transcriptional activity of the Nod2 promoter.
      Upon stimulation with TNFalpha or lipopolysaccharide, both p50 and p65 subunits
      of NF-kappaB were bound to the Nod2 promoter. Thus, Nod2 expression is enhanced
      by proinflammatory cytokines and bacterial components via NF-kappaB, a mechanism
      that may contribute to the amplification of the innate immune response and
      susceptibility to inflammatory disease.

PMID- 12194983
TI  - The molecular mechanism of multidrug resistance by the Q151M human
      immunodeficiency virus type 1 reverse transcriptase and its suppression using
      alpha-boranophosphate nucleotide analogues.
AB  - Nucleoside analogues are currently used to treat human immunodeficiency virus
      infections. The appearance of up to five substitutions (A62V, V75I, F77L, F116Y,
      and Q151M) in the viral reverse transcriptase promotes resistance to these drugs,
      and reduces efficiency of the antiretroviral chemotherapy. Using pre-steady state
      kinetics, we show that Q151M and A62V/V75I/F77L/F116Y/Q151M substitutions confer
      to reverse transcriptase (RT) the ability to discriminate an analogue relative to
      its natural counterpart, and have no effect on repair of the analogue-terminated
      DNA primer. Discrimination results from a selective decrease of the catalytic
      rate constant k(pol): 18-fold (from 7 to 0.3 s(-1)), 13-fold (from 1.9 to 0.14 s(
      1)), and 12-fold (from 13 to 1 s(-1)) in the case of ddATP, ddCTP, and 3'-azido
      3'-deoxythymidine 5'-triphosphate (AZTTP), respectively. The binding affinities
      of the triphosphate analogues for RT remain unchanged. Molecular modeling
      explains drug resistance by a selective loss of electrostatic interactions
      between the analogue and RT. Resistance was overcome using alpha-boranophosphate
      nucleotide analogues. Using A62V/V75I/F77L/F116Y/Q151M RT, k(pol) increases up to
      70- and 13-fold using alpha-boranophosphate-ddATP and alpha-boranophosphate
      AZTTP, respectively. These results highlight the general capacity of such
      analogues to circumvent multidrug resistance when RT-mediated nucleotide
      resistance originates from the selective decrease of the catalytic rate constant
      k(pol).

PMID- 12194984
TI  - Syndecan-3 is a selective regulator of chondrocyte proliferation.
AB  - Chondrocyte proliferation is important for skeletal development and growth, but
      the mechanisms regulating it are not completely clear. Previously, we showed that
      syndecan-3, a cell surface heparan sulfate proteoglycan, is expressed by
      proliferating chondrocytes in vivo and that proliferation of cultured
      chondrocytes in vitro is sensitive to heparitinase treatment. To further
      establish the link between syndecan-3 and chondrocyte proliferation, additional
      studies were carried out in vivo and in vitro. We found that the topographical
      location of proliferating chondrocytes in developing chick long bones changes
      with increasing embryonic age and that syndecan-3 gene expression changes in a
      comparable manner. For in vitro analysis, mitotically quiescent chondrocytes were
      exposed to increasing amounts of fibroblast growth factor-2 (FGF-2).
      Proliferation was stimulated by as much as 8-10-fold within 24 h; strikingly,
      this stimulation was significantly prevented when the cells were treated with
      both fibroblast growth factor-2 (FGF-2) and antibodies against syndecan-3 core
      protein. This neutralizing effect was dose-dependent and elicited a maximum of 50
      60% inhibition. To establish specificity of neutralizing effect, cultured
      chondrocytes were exposed to FGF-2, insulin-like growth factor-1, or parathyroid
      hormone, all known mitogens for chondrocytes. The syndecan-3 antibodies
      interfered only with FGF-2 mitogenic action, but not that of insulin-like growth
      factor-1 or parathyroid hormone. Protein cross-linking experiments indicated that
      syndecan-3 is present in monomeric, dimeric, and oligomeric forms on the
      chondrocyte surface. In addition, molecular modeling indicated that contiguous
      syndecan-3 molecules might form stable complexes by parallel pairing of beta
      sheet segments within the ectodomain of the core protein. In conclusion, the
      results suggest that syndecan-3 is a direct and selective regulator of the
      mitotic behavior of chondrocytes and its role may involve formation of
      dimeric/oligomeric structures on their cell surface.

PMID- 12194985
TI  - The role of putative phosphorylation sites in the targeting and shuttling of the
      aquaporin-2 water channel.
AB  - In renal collecting ducts, a vasopressin-induced cAMP increase results in the
      phosphorylation of aquaporin-2 (AQP2) water channels at Ser-256 and its
      redistribution from intracellular vesicles to the apical membrane. Hormones that
      activate protein kinase C (PKC) proteins counteract this process. To determine
      the role of the putative kinase sites in the trafficking and hormonal regulation
      of human AQP2, three putative casein kinase II (Ser-148, Ser-229, Thr-244), one
      PKC (Ser-231), and one protein kinase A (Ser-256) site were altered to mimic a
      constitutively non-phosphorylated/phosphorylated state and were expressed in
      Madin-Darby canine kidney cells. Except for Ser-256 mutants, seven correctly
      folded AQP2 kinase mutants trafficked as wild-type AQP2 to the apical membrane
      via forskolin-sensitive intracellular vesicles. With or without forskolin, AQP2
      Ser-256A was localized in intracellular vesicles, whereas AQP2-S256D was
      localized in the apical membrane. Phorbol 12-myristate 13-acetate-induced PKC
      activation following forskolin treatment resulted in vesicular distribution of
      all AQP2 kinase mutants, while all were still phosphorylated at Ser-256. Our data
      indicate that in collecting duct cells, AQP2 trafficking to vasopressin-sensitive
      vesicles is phosphorylation-independent, that phosphorylation of Ser-256 is
      necessary and sufficient for expression of AQP2 in the apical membrane, and that
      PMA-induced PKC-mediated endocytosis of AQP2 is independent of the AQP2
      phosphorylation state.

PMID- 12194986
TI  - Calcium regulation of matrix metalloproteinase-mediated migration in oral
      squamous cell carcinoma cells.
AB  - Activation of matrix metalloproteinase 2 (MMP-2) has been shown to play a
      significant role in the behavior of cancer cells, affecting both migration and
      invasion. The activation process requires multimolecular complex formation
      involving pro-MMP-2, membrane type 1-MMP (MT1-MMP), and tissue inhibitor of
      metalloproteinases-2 (TIMP-2). Because calcium is an important regulator of
      keratinocyte function, we evaluated the effect of calcium on MMP regulation in an
      oral squamous cell carcinoma line (SCC25). Increasing extracellular calcium (0.09
      1.2 mm) resulted in a dose-dependent increase in MT1-MMP-dependent pro-MMP-2
      activation. Despite the requirement for MT1-MMP in the activation process, no
      changes in MT1-MMP expression, cell surface localization, or endocytosis were
      apparent. However, increased generation of the catalytically inactive 43-kDa MT1
      MMP autolysis product and decline in the TIMP-2 levels in conditioned media were
      observed. The decrease in TIMP-2 levels in the conditioned media was prevented by
      a broad spectrum MMP inhibitor, suggesting that calcium promotes recruitment of
      TIMP-2 to MT1-MMP on the cell surface. Despite the decline in soluble TIMP-2, no
      accumulation of TIMP-2 in cell lysates was seen. Blocking TIMP-2 degradation with
      bafilomycin A1 significantly increased cell-associated TIMP-2 levels in the
      presence of high calcium. These data suggest that the decline in TIMP-2 is
      because of increased calcium-mediated MT1-MMP-dependent degradation of TIMP-2. In
      functional studies, increasing calcium enhanced MMP-dependent cellular migration
      on laminin-5-rich matrix using an in vitro colony dispersion assay. Taken
      together, these results suggest that changes in extracellular calcium can
      regulate post-translational MMP dynamics and thus affect the cellular behavior of
      oral squamous cell carcinoma.

PMID- 12194987
TI  - Low density lipoprotein (LDL) receptor-related protein 1B impairs urokinase
      receptor regeneration on the cell surface and inhibits cell migration.
AB  - The low density lipoprotein (LDL) receptor-related protein 1B (LRP1B) is a newly
      identified member of the LDL receptor family and is closely related to LRP. It
      was discovered as a putative tumor suppressor and is frequently inactivated in
      lung cancer cells. In the present study, we used an LRP1B minireceptor (mLRP1B4),
      which mimics the function and trafficking of LRP1B, to explore the roles of LRP1B
      on the plasminogen activation system. We found that mLRP1B4 and urokinase
      plasminogen activator receptor (uPAR) form immunoprecipitable complexes on the
      cell surface in the presence of complexes of uPA and its inhibitor, plasminogen
      activator inhibitor type-1 (PAI-1). However, compared with cells expressing the
      analogous LRP minireceptor (mLRP4), cells expressing mLRP1B4 display a
      substantially slower rate of uPA.PAI-1 complex internalization. Expression of
      mLRP1B4, or an mLRP4 mutant deficient in endocytosis, leads to an accumulation of
      uPAR at the cell surface and increased cell-associated uPA and PAI-1 when
      compared with cells expressing mLRP4. In addition, we found that expression of
      mLRP1B or the mLRP4 endocytosis mutant impairs the regeneration of unoccupied
      uPAR on the cell surface and that this correlates with a diminished rate of cell
      migration. Taken together, these results demonstrate that LRP1B can function as a
      negative regulator of uPAR regeneration and cell migration.

PMID- 12194988
TI  - Genetics of myeloid leukemias.
AB  - Human leukemias are typified by acquired recurring chromosomal translocations.
      Cloning of these translocation breakpoints has provided important insights into
      pathogenesis of disease as well as novel therapeutic approaches. Chronic
      myelogenous leukemias (CML) are caused by constitutively activated tyrosine
      kinases, such as BCR/ABL, that confer a proliferative and survival advantage to
      hematopoietic progenitors but do not affect differentiation. These activated
      kinases are validated targets for therapy with selective tyrosine kinase
      inhibitors, a paradigm that may have broad applications in treatment of
      hematologic malignancies as well as solid tumors. Chromosomal translocations in
      acute myeloid leukemias (AML) most often result in loss-of-function mutations in
      transcription factors that are required for normal hematopoietic development.
      These latter mutations, however, are not sufficient to cause AML. The available
      evidence indicates that activating mutations in the hematopoietic tyrosine
      kinases FLT3 and c-KIT, and in N-RAS and K-RAS, confer proliferative advantage to
      hematopoietic progenitors and cooperate with loss-of-function mutations in
      hematopoietic transcription factors to cause an acute leukemia phenotype
      characterized by proliferation and impaired differentiation. The data supporting
      this hypothesis and the clinical and therapeutic implications of these
      observations are reviewed.

PMID- 12194989
TI  - Structuring the universe of proteins.
AB  - High-throughput sequencing of human genomes and those of important model
      organisms (mouse, Drosophila melanogaster, Caenorhabditis elegans, fungi,
      archaea) and bacterial pathogens has laid the foundation for another "big
      science" initiative in biology. Together, X-ray crystallographers, nuclear
      magnetic resonance (NMR) spectroscopists, and computational biologists are
      pursuing high-throughput structural studies aimed at developing a comprehensive
      three-dimensional view of the protein structure universe. The new science of
      structural genomics promises more than 10,000 experimental protein structures and
      millions of calculated homology models of related proteins. The evolutionary
      underpinnings and technological challenges of automating target selection,
      protein expression and purification, sample preparation, NMR and X-ray data
      measurement/analysis, homology modeling, and structure/function annotation are
      discussed in detail. An informative case study from one of the structural
      genomics centers funded by the National Institutes of Health and the National
      Institute of General Medical Sciences (NIH/NIGMS) demonstrates how this
      experimental/computational pipeline will reveal important links between form and
      function in biology and provide new insights into evolution and human health and
      disease.

PMID- 12194990
TI  - Databases and tools for browsing genomes.
AB  - To maximize the value of genome sequences they need to be integrated with other
      types of biological data and with each other. The entire collection of data then
      needs to be made available in a way that is easy to view and mine for complex
      relationships. The recently determined vertebrate genome sequences of human and
      mouse are so large that building the infrastructure to manage these datasets is a
      major challenge. This article reviews the database systems and tools for analysis
      that have so far been developed to address this.

PMID- 12194991
TI  - Changes produced in the urothelium by traditional and newer therapeutic
      procedures for bladder cancer.
AB  - A handful of traditional and newer therapeutic procedures, such as chemotherapy,
      immunotherapy, radiotherapy, photodynamic and laser treatment, and gene therapy,
      are used to treat epithelial malignancies of bladder origin. These treatment
      modalities, used either intravesically or systemically, produce morphological
      changes in the urothelial mucosa that can be mistaken for carcinoma. The
      pathologist must be able to separate toxic and drug related alterations from
      tumour related changes. The clinical history is usually invaluable in this
      assessment.

PMID- 12194994
TI  - Effect of beta propiolactone viral inactivation on alpha1 antitrypsin values.
AB  - AIMS: alpha1 Antitrypsin was undetectable in several patient samples treated with
      0.5% beta propiolactone, which was used as a virucidal agent. This study was
      designed to confirm beta propiolactone as the cause and determine why it might
      have such an effect. METHODS: Volumes of 0, 5, 10, and 20 micro l of beta
      propiolactone were added to 2 ml aliquots of serum to make final concentrations
      of 0%, 0.25%, 0.5%, and 1% of beta propiolactone. alpha1 Antitrypsin
      concentrations and the pH were measured at different time intervals. The effects
      of adding buffer before the addition of beta propiolactone, NaOH after beta
      propiolactone, and 6M HCl instead of beta propiolactone were also measured.
      RESULTS: The addition of beta propiolactone to a volunteer's serum showed a fall
      in both alpha1 antitrypsin values and pH with increasing time and concentration
      of beta propiolactone. This effect was also seen when adding HCl, but was
      partially prevented by buffering the serum or adding NaOH. CONCLUSIONS: These
      results suggest that it is the acidity of the degradation products of beta
      propiolactone that is responsible for the fall in alpha1 antitrypsin values. This
      fall in alpha1 antitrypsin values was dependent on the concentration of beta
      propiolactone used and the length of time before the test was performed. The
      effect of beta propiolactone on laboratory tests should be re-evaluated, with
      attention being paid to sample pH, storage time, and storage temperature.

PMID- 12194993
TI  - HER-2/neu expression in germ cell tumours.
AB  - AIMS: To determine the rate of HER-2/neu positivity of germ cell tumours by
      immunohistochemistry (IHC) and by fluorescence in situ hybridisation (FISH).
      PATIENTS/METHODS: Ninety six archival, paraffin wax embedded pathology specimens
      were chosen from four groups of germ cell tumours. IHC for HER-2/neu was
      performed with the HercepTest kit; FISH analysis was performed with the INFORM
      assay and confirmed with a centromere 17 probe. RESULTS: Twenty two of 96
      specimens overexpressed the HER-2/neu protein when measured by IHC. Only three
      specimens showed HER-2/neu gene amplification by FISH. There was no correlation
      between the results obtained by IHC and FISH. CONCLUSIONS: The lack of
      concordance between IHC and FISH makes it unlikely that overexpression of the HER
      2/neu protein in germ cell tumours is of prognostic or therapeutic relevance.
      Because of the low rate of HER-2/neu gene amplification in germ cell tumours, a
      clinical trial of trastuzumab treatment in patients with germ cell tumours is not
      warranted.

PMID- 12194992
TI  - Cell kinetics and cell cycle regulation in lymphomas.
AB  - The proliferative indices of non-Hodgkin's lymphomas are useful prognostic
      indicators and provide information independent of other histological and clinical
      variables. However, proliferative indices alone do not suffice to characterise
      cell growth. A high cell production rate may be compensated, almost or fully, by
      a high cell deletion rate. A re-evaluation of parameters of cell kinetics in view
      of our increasing knowledge of the molecular pathways of cell cycle control may
      provide more prognostic information for the management of patients with malignant
      lymphomas.

PMID- 12194995
TI  - Immunohistochemistry in the distinction between malignant mesothelioma and
      pulmonary adenocarcinoma: a critical evaluation of new antibodies.
AB  - AIM: The value of immunohistochemical staining in differentiating between
      malignant mesothelioma and pulmonary adenocarcinoma was re-examined using newly
      available commercial antibodies, with the aim of increasing the sensitivity and
      specificity of diagnosis, and simplifying the antibody panel required. METHODS:
      Forty one malignant mesotheliomas and 35 lung adenocarcinomas were studied.
      Commercial antibodies to calretinin, E-cadherin, N-cadherin, surfactant
      apoprotein A (SP-A), thyroid transcription factor 1 (TTF-1), thrombomodulin, and
      cytokeratin 5/6 were applied using the streptavidin-biotin-peroxidase complex
      procedure on formalin fixed, paraffin wax embedded tissue. RESULTS: E-cadherin
      was expressed in all adenocarcinomas and in 22% of the mesotheliomas. TTF-1
      expression was detected in 69% of the adenocarcinomas and none of the
      mesotheliomas. Positive staining with polyclonal anticalretinin was detected in
      80% of the mesotheliomas and 6% of the adenocarcinomas. N-cadherin was expressed
      in 78% of mesotheliomas and 26% of adenocarcinomas. Thrombomodulin was expressed
      in 6% of the adenocarcinomas and in 53% of the mesotheliomas. Cytokeratin 5/6
      expression was detected in 6% of the adenocarcinomas and 63% of the
      mesotheliomas. The results were compared with the standard laboratory panel for
      mesothelioma diagnosis: anticarcinoembryonic antigen (anti-CEA), LeuM1, BerEP4,
      and HBME-1. CONCLUSION: Of the antibodies used in this study, E-cadherin was 100%
      sensitive for pulmonary adenocarcinoma and TTF-1 was 100% specific for pulmonary
      adenocarcinoma. The application of these two antibodies alone was adequate for
      the diagnosis of 69% of adenocarcinomas and 78% of mesotheliomas. Where TTF-1 is
      negative and E-cadherin is positive, a secondary panel of antibodies, including
      BerEP4 and LeuM1 (CD15) and antibodies directed against CEA, calretinin,
      cytokeratin 5/6, thrombomodulin, and N-cadherin, is required for differentiation
      between malignant mesothelioma and pulmonary adenocarcinoma.

PMID- 12194997
TI  - Hepatic veno-occlusive disease as a result of a traditional remedy: confirmation
      of toxic pyrrolizidine alkaloids as the cause, using an in vitro technique.
AB  - BACKGROUND/AIMS: A child presented with hepatic veno-occlusive disease after
      having been administered a short course of treatment with a traditional herbal
      remedy. The child subsequently died. Postmortem liver histology confirmed the
      diagnosis. This study aimed to investigate the hypothesis that the herbal remedy
      was the cause of veno-occlusive disease. METHODS: Extracts of the traditional
      remedy were analysed by colorimetry and gas chromatography/mass spectrometry.
      Cultured hepatocytes were treated with an extract of the plant material and
      examined for morphological changes. RESULTS: The screening analyses indicated the
      presence of toxic pyrrolizidine alkaloids, which were later confirmed by gas
      chromatography/mass spectrometry. The cell studies indicated dose related
      toxicity, with necrosis at high concentrations and apoptosis and abnormalities of
      the cytoskeleton at lower concentrations. CONCLUSIONS: The simple screening
      techniques used allowed rapid confirmation of the presence of toxic
      pyrrolizidines in the remedy. The in vitro method confirmed the toxicity of
      herbal extracts to hepatocytes.

PMID- 12194998
TI  - Immunofluorescent patterns produced by antineutrophil cytoplasmic antibodies
      (ANCA) vary depending on neutrophil substrate and conjugate.
AB  - BACKGROUND: The "International consensus statement on testing and reporting
      antineutrophil cytoplasmic antibodies (ANCA)" advocates screening by indirect
      immunofluorescence (IIF), but external quality assessment programmes often
      demonstrate different IIF patterns for a single serum. AIM: To determine whether
      the variation in IIF patterns can be attributed solely to errors in
      interpretation. METHODS: This study compared the IIF patterns produced by four
      sera (two with cytoplasmic or C-ANCA; one with perinuclear or P-ANCA with
      myeloperoxidase (MPO) specificity; and one P-ANCA without MPO specificity) that
      were tested in 11 different laboratories. The sera were examined according to
      individual laboratory protocols at dilutions of 1/10 to 1/40 using P1 (n = 4), P2
      (n = 2), P3 (n = 2), or in house (n=3) neutrophil preparations and conjugates
      from manufacturers C1 (n = 3), C2 (n = 1), C3 (n = 2), C4 (n = 1), C5 (n = 2),
      and C6 (n = 2). The IIF patterns were noted in each laboratory, the testing
      repeated, and the fluorescent patterns photographed and subsequently discussed at
      a meeting of the Australian ANCA study group. RESULTS: All IIF patterns described
      in individual laboratories were confirmed on retesting and by the ANCA study
      group. Neutrophil substrates produced commercially or in house varied in their
      ability to demonstrate cytoplasmic granularity and interlobular accentuation,
      which distinguish between "C-ANCA" and "C-ANCA (atypical)". All commercial and in
      house neutrophil substrates demonstrated neutrophil nuclear extension of P-ANCA
      fluorescence, which correlates with MPO specificity. However, eight assays (eight
      of 43) from eight laboratories resulted in IIF patterns different from those
      usually seen. One of these produced a C-ANCA (atypical) rather than a C-ANCA
      pattern. The other seven resulted in at least some cytoplasmic fluorescence when
      the consensus pattern was P-ANCA with (n = 4) or without (n = 3) MPO specificity.
      These assays used three different commercial and one in house neutrophil
      substrate, and six different conjugates, with anti-IgG, anti-(Fab)'(2), anti-Ig
      (heavy and light chain), and anti-G, A, and M activity. Four of the seven assays
      tested on commercial substrates had used the manufacturer's conjugates.
      CONCLUSIONS: This study indicates that the variation in IIF patterns seen with
      ANCA positive sera tested in different laboratories does not necessarily result
      from errors in the interpretation of patterns and cannot be attributed solely to
      the use of a particular neutrophil substrate or conjugate, or to the use of
      substrate from one manufacturer and conjugate from another.

PMID- 12194996
TI  - Epstein-Barr virus in gastric adenocarcinomas: association with ethnicity and
      CDKN2A promoter methylation.
AB  - AIMS: It has been shown previously (by immunohistochemistry) that gastric
      adenocarcinomas harbouring Epstein-Barr virus (EBV) frequently lose p16 protein.
      This study aimed to examine the mechanisms of inactivation of the CDKN2A gene and
      correlate the results with clinicopathological features. METHODS: Methylation
      specific polymerase chain reaction was used to detect CDKN2A promoter methylation
      in gastric adenocarcinomas from American patients. In addition,
      immunohistochemistry was used to detect the loss of the p16 protein and in situ
      hybridisation was used to detect the presence of EBV. The tumours were also
      analysed for the presence of microsatellite instability. RESULTS: Eleven (10%) of
      107 tumours harboured EBV in the malignant cells. In gastric cancers without EBV,
      32% exhibited CDKN2A promoter methylation and 26% had p16 protein loss. In
      contrast, 91% of the tumours containing EBV had CDKN2A promoter methylation (p =
      0.0003) and 90% showed p16 protein loss (p = 0.0001). The presence of EBV was
      also associated with male sex (p = 0.03) and was more common in tumours from
      Texas Hispanics than from non-Hispanic whites or African-Americans (p = 0.01).
      EBV was not associated with microsatellite instability, histological subtype,
      stage, or grade of the tumour, or age or survival time of the patient.
      CONCLUSIONS: The presence of EBV in gastric adenocarcinomas is strongly
      associated with CDKN2A inactivation by promoter methylation. In addition, these
      findings suggest that there are ethnic differences in tumour virology and
      pathogenesis.

PMID- 12194999
TI  - Primary follicular lymphoma of the testis in childhood: an entity with peculiar
      clinical and molecular characteristics.
AB  - BACKGROUND/AIMS: Paediatric primary follicular lymphoma of the testis (PPFLT) is
      exceptional: the few reported cases seem to lack BCL-2 gene rearrangement and/or
      protein expression. The aim of this study was to characterise a PPFLT arising in
      a 4 year old boy. METHODS: This case was characterised using conventional
      histological analysis, immunohistochemistry, and a polymerase chain reaction
      based method for the detection of immunoglobulin V(H) chain rearrangements.
      RESULTS: The neoplasm was staged I(E)/A; left orchiectomy and chemotherapy were
      performed, producing complete remission. Histology showed a predominantly
      follicular lymphoid infiltrate mainly composed of centroblast-like cells. The
      phenotype was CD20(+), CD79a(+), CD10(+), bcl-6(+), B cell specific activating
      protein(+), kappa light chain(+), CD30(-/+), interferon regulating factor 4(-/+),
      c-myc(-/+), lambda light chain(-), CD3(-), bcl-2(-), p53(-), cytokeratin(-), and
      placental alkaline phosphatase(-). Lymphomatous elements were found within a
      CD21(+) follicular dendritic cell network and 70% were positive for Ki-67/MIB-1.
      Molecular analysis revealed monoclonal immunoglobulin heavy chain gene
      rearrangement and BCL-6 mutations, in the absence of BCL-2 major breakpoint and
      BCL-2 minor cluster region rearrangements, p53 mutations, and death associated
      protein kinase gene hypermethylation. CONCLUSIONS: These findings suggest a
      different pathogenesis of PPTFL compared with adult follicular lymphoma and might
      explain its favourable course in spite of aggressive histology.

PMID- 12195000
TI  - Non-alcoholic steatohepatitis: a common cause of progressive chronic liver
      injury?
AB  - AIM: To investigate the natural history of patients with non-alcoholic
      steatohepatitis by means of a prospective histological study. METHODS: One
      thousand five hundred and seventy one patients underwent liver biopsy at the
      Western Infirmary in Glasgow during the 10 year period 1985 to 1994. All biopsies
      were reported by a single pathologist: 62 were confirmed as having non-alcoholic
      steatohepatitis and prospective follow up was conducted in 1999. Repeat liver
      biopsy was carried out where appropriate to assess disease progression. RESULTS:
      Initial biopsy scores for the 62 patients (20 men; mean age at biopsy, 52 years)
      showed a mean of 1.85, 1.39, and 0.5 for necroinflammation, fibrosis, and iron
      stores, respectively. Forty six were traceable and invited for review, and 26
      attended (six men; mean age at initial biopsy, 49.9 years) at a mean of 8.7 years
      after the initial liver biopsy. No patients had symptoms or signs of chronic
      liver disease. Four patients had normal liver function tests, one had cirrhosis;
      the remaining 21 were invited to have a repeat biopsy. Seven patients agreed, a
      mean 8.2 years after the initial biopsy, and repeat biopsy scores showed no
      significant difference over this time period, with mean scores of 1.71 (initial
      score, 2.14), 1.43 (initial score, 0.71), and 0.14 (initial score, 0) for
      necroinflammation, fibrosis, and iron stores, respectively. CONCLUSION: In this
      series of patients with non-alcoholic steatohepatitis, with a mean clinical
      follow up of 8.7 years, and a histological follow up of 8.2 years, there was no
      evidence of progressive chronic liver injury.

PMID- 12195001
TI  - Adipocytic proportion of bone marrow is inversely related to bone formation in
      osteoporosis.
AB  - AIMS: Preliminary studies have suggested that there is an increase in adipocytic
      tissue in osteoporotic (OP) bone, supporting in vitro evidence for a switch in
      differentiation of stromal cells from the osteoblastic to the adipocytic lineage.
      To investigate this the variation of the ratio of adipose tissue to
      haemopoietic/stromal tissue in OP bone was measured. METHODS: The ratio of
      adipocytic to haemopoietic/stromal tissue (A/H) was measured by semi-automated
      image analysis in iliac crest biopsies from 127 patients with osteoporosis (84
      female patients, 48 male patients; mean age, 55 years; range, 5-80). Fourteen
      patients with normal histomorphometric data (nine women; five men; mean age, 48
      years; range 21-70) acted as controls. RESULTS: The ratio of A/H was higher in OP
      bone than in the normal controls (OP mean 43.06% v normal mean 22.4%; p < 0.001).
      Multiple regression analysis showed that 98.5% of the variability in the A/H
      ratio was the result of age and several measures of bone formation, including
      cancellous wall thickness, osteoid volume, cancellous thickness, cortical wall
      thickness, cancellous apposition rate, and bone formation rate, together with
      cancellous separation (each significant at p < 0.001). Those with the greatest
      effect on the A/H ratio (in decreasing order) were cancellous apposition rate,
      osteoid volume, and age. CONCLUSIONS: Cancellous apposition rate, osteoid volume,
      and age were associated with the increase in the proportion of adipose tissue
      present in OP bone. Of these, cancellous apposition rate reflects osteoblast
      activity, indicating that the increase in the volume of adipose tissue in
      osteoporosis is associated with reduced bone formation, supporting the postulated
      switch in differentiation of stromal cells from the osteoblastic to the
      adipocytic pathway in osteoporosis.

PMID- 12195002
TI  - Silent haemoglobin variants and determination of HbA(1c) with the HPLC Bio-Rad
      Variant II.
AB  - AIMS: To evaluate the determination of HbA(1c) with an automated high performance
      liquid chromatography (HPLC) method in patients with clinically silent
      haemoglobin variants. METHODS: HbA(1c) values were determined with the ion
      exchange HPL Bio-Rad Variant II using the high resolution beta thalassaemia
      programme in patients with silent haemoglobin variants, namely: Hb Graz, Hb
      Sherwood Forest, Hb O Padova, and Hb D. RESULTS: All of these haemoglobin
      variants caused additional peaks in the chromatograms. No clinically useful
      HbA(1c) results were produced for patients with Hb Graz and Hb Sherwood Forest,
      the results for the patient with Hb D were too low, but the results for patients
      with Hb O Padova were acceptable. CONCLUSIONS: The development of this automated
      HPLC method modification with high resolution mode aids the identification of
      interference caused by the described clinically silent haemoglobin variants in
      HbA(1c) determination.

PMID- 12195003
TI  - Increase in alcohol related deaths: is hepatitis C a factor?
AB  - AIM: To evaluate recent trends in alcohol related deaths in the UK and to
      consider possible causative factors. DESIGN: Observational retrospective study of
      the database of the Office for National Statistics, alcohol consumption data
      reported by the General Household Survey, and other published data. SETTING:
      England, 1993-9. RESULTS: Deaths for each million of the population from alcohol
      related illness increased by 59% in men and 40% in women over the years 1993 to
      1999. One subgroup of alcohol related deaths, ICD 571.3 (alcoholic liver damage
      unspecified), showed a 243% increase in men aged 40 to 49 years over the same
      period. Figures for younger men, and women in all age groups, showed less
      pronounced increases. There has been no associated rise in alcohol intake. There
      has been an increase in the incidence of hepatitis C virus (HCV) infection in
      recent years, and alcohol consumption in HCV positive individuals accelerates the
      progression to cirrhosis. Circumstantial evidence links the rise in HCV infection
      to the use of illicit drugs in the 1970s and 1980s, among those currently aged 40
      to 59 years. CONCLUSIONS: The recent increase in alcohol related deaths cannot be
      solely explained by a change in drinking habits. It is suggested that this
      probably results from the rapid progression of alcoholic cirrhosis in people who
      have acquired HCV infection through intravenous drug use. Alcohol consumption in
      HCV positive individuals is firmly linked with a poor outcome.

PMID- 12195004
TI  - Colonic carcinoma with granulomatous (sarcoid) reaction.
AB  - A 74 year old man had a right hemicolectomy for a caecal adenocarcinoma.
      Microscopic examination also revealed non-caseating epithelioid granulomatas
      within the adjacent stroma and some of these granulomata contained centrally
      located malignant cells. Granulomatous inflammation was not present within the
      lymph nodes and the importance of this rare occurrence is discussed.

PMID- 12195006
TI  - A tumour with a neuroendocrine and papillary serous component: two or a pair?
AB  - AIMS: To examine the clonal origin of a tumour, made up of a neuroendocrine
      component and a papillary serous component by comparing the pattern of loss of
      heterozygosity (LOH) and the immunohistochemical protein expression of both
      components. METHODS/RESULTS: A 70 year old woman, known to have a metastasised
      neuroendocrine carcinoma, underwent resection of the distal part of the ileum
      because of obstruction by a mesenterial mass. The macroscopically homogeneous
      mesenterial mass consisted histologically of an admixture of a neuroendocrine
      component and a papillary serous carcinoma. Loss of heterozygosity (LOH) analysis
      of both components with a panel of 15 polymorphic microsatellite markers showed a
      distinctive pattern of LOH, and both components showed LOH on chromosome 4q and
      17, but involving different alleles at the same locus. Moreover, both components
      showed different immunohistochemical staining patterns for neuroendocrine
      markers, cytokeratin 7, carcinoembryonic antigen, and CA125. CONCLUSION: Both LOH
      analysis of the neuroendocrine and papillary serous components of this tumour and
      the immunohistochemical profile of both components are consistent with a
      different clonal origin. The tumour is probably a collision tumour, in which the
      papillary serous carcinoma must have been of peritoneal origin because necropsy
      revealed a normal uterus and normal ovaries.

PMID- 12195007
TI  - Endometrial cyst of the liver: a case report and review of the literature.
AB  - The occurrence of pelvic endometriosis is not uncommon but hepatic endometriosis
      is extremely rare. Only five such cases of hepatic endometriosis have been
      described in the literature. This report concerns another patient with hepatic
      endometriosis forming a large cystic mass. The clinicopathological features and
      the possible pathogenesis are discussed. Endometriosis should be considered in
      the differential diagnosis of a cystic liver mass, particularly in patients with
      known endometriosis.

PMID- 12195008
TI  - Paradoxical severe decrease in serum HDL-cholesterol after treatment with a
      fibrate.

PMID- 12195009
TI  - A pathological study of tumour regression in oesophageal adenocarcinoma treated
      with preoperative chemoradiotherapy.

PMID- 12195010
TI  - The use of a standard proforma in breast cancer reporting.

PMID- 12195011
TI  - Conversion to core biopsy in preoperative diagnosis of breast lesions: is it
      justified by results?

PMID- 12195013
TI  - Genomic expression programs and the integration of the CD28 costimulatory signal
      in T cell activation.
AB  - Optimal activation of T cells requires effective occupancy of both the antigen
      specific T cell receptor and a second coreceptor such as CD28. We used cDNA
      microarrays to characterize the genomic expression program in human peripheral T
      cells responding to stimulation of these receptors. We found that CD28 agonists
      alone elicited few, but reproducible, changes in gene expression, whereas CD3
      agonists elicited a multifaceted temporally choreographed gene expression
      program. The principal effect of simultaneous engagement of CD28 was to increase
      the amplitude of the CD3 transcriptional response. The induced genes whose
      expression was most enhanced by costimulation were significantly enriched for
      known targets of nuclear factor of activated T cells (NFAT) transcription
      factors. This enhancement was nearly abolished by blocking the nuclear
      translocation of NFATc by using the calcineurin inhibitor FK506. CD28 signaling
      promoted phosphorylation, and thus inactivation, of the NFAT nuclear export
      kinase glycogen synthase kinase-3 (GSK3), coincident with enhanced
      dephosphorylation of NFATc proteins. These results provide a detailed picture of
      the transcriptional program of T cell activation and suggest that enhancement of
      transcriptional activation by NFAT, through inhibition of its nuclear export,
      plays a key role in mediating the CD28 costimulatory signal.

PMID- 12195015
TI  - Modulation of TCR-induced transcriptional profiles by ligation of CD28, ICOS, and
      CTLA-4 receptors.
AB  - Signals generated by T cell receptor (TCR) and CD28 engagement are required for
      optimal T cell activation, but how these signals integrate within the cell is
      still largely unknown. We have used near genome-scale expression profiling to
      monitor T cell signal transduction pathways triggered via TCR and/or
      costimulatory receptors. Ligation of CD28 alone induced a set of short-lived
      early response transcripts in both Jurkat T cells and primary CD4 T cells, thus
      providing evidence that CD28 engagement can affect gene regulation independently
      of TCR engagement. Simultaneous signaling through both the TCR and CD28 resulted
      in altered expression of several thousand genes following several distinct
      temporal patterns. Most of these gene regulations were induced by TCR signaling
      alone and were augmented to varying degrees by CD28 costimulation. CD28 and ICOS
      costimulation had nearly identical effects on gene regulation, but a few
      transcripts (e.g., IL2, IL9) were significantly more affected by CD28. Therefore,
      the distinctive functional outcomes of costimulation via CD28 and ICOS are
      accompanied by relatively few distinct differences in gene expression. Cytotoxic
      T lymphocyte antigen 4 (CTLA-4) engagement selectively blocked augmentation of
      gene regulations by CD28-mediated costimulation, but did not ablate gene
      regulation induced by TCR triggering alone.

PMID- 12195014
TI  - The novel Rho-GTPase activating gene MEGAP/ srGAP3 has a putative role in severe
      mental retardation.
AB  - In the last few years, several genes involved in X-specific mental retardation
      (MR) have been identified by using genetic analysis. Although it is likely that
      additional genes responsible for idiopathic MR are also localized on the
      autosomes, cloning and characterization of such genes have been elusive so far.
      Here, we report the isolation of a previously uncharacterized gene, MEGAP, which
      is disrupted and functionally inactivated by a translocation breakpoint in a
      patient who shares some characteristic clinical features, such as hypotonia and
      severe MR, with the 3p(-) syndrome. By fluorescence in situ hybridization and
      loss of heterozygosity analysis, we demonstrated that this gene resides on
      chromosome 3p25 and is deleted in 3p(-) patients that present MR. MEGAP/srGAP3
      mRNA is predominantly and highly expressed in fetal and adult brain, specifically
      in the neurons of the hippocampus and cortex, structures known to play a pivotal
      role in higher cognitive function, learning, and memory. We describe several
      MEGAP/srGAP3 transcript isoforms and show that MEGAP/srGAP3a and -b represent
      functional GTPase-activating proteins (GAP) by an in vitro GAP assay.
      MEGAP/srGAP3 has recently been shown to be part of the Slit-Robo pathway
      regulating neuronal migration and axonal branching, highlighting the important
      role of MEGAP/srGAP3 in mental development. We propose that haploinsufficiency of
      MEGAP/srGAP3 leads to the abnormal development of neuronal structures that are
      important for normal cognitive function.

PMID- 12195016
TI  - VEGF increases engraftment of bone marrow-derived endothelial progenitor cells
      (EPCs) into vasculature of newborn murine recipients.
AB  - Recent evidence suggests that bone marrow-derived angioblasts or endothelial
      progenitor cells circulate in peripheral blood and can incorporate at sites of
      pathologic neovascularization or during the ovarian cycle. However, the
      incorporation of endothelial progenitor cells into vessels of nonischemic tissues
      in adult animals has not been observed. We hypothesized that the vascular
      microenvironment differs between newborn and adult animals, and that donor
      endothelial cell progenitors would engraft in rapidly growing normal tissues
      during the neonatal period. After nonablative administration of bone marrow cells
      either at birth or at 4 weeks of age, donor-derived endothelial cells were found
      only in the neovasculature of the newborn recipients. Both the incorporation of
      donor endothelial cells into the newborn neovasculature as well as tissue
      vascularity were significantly increased by coadministering vascular endothelial
      growth factor with bone marrow cells. These findings suggest that bone marrow
      derived endothelial progenitor cells can contribute to neovascularization during
      the newborn period and are responsive to vascular endothelial growth factor.

PMID- 12195018
TI  - Tyrosine phosphorylation in plant cell signaling.

PMID- 12195017
TI  - Direct evidence for a G-quadruplex in a promoter region and its targeting with a
      small molecule to repress c-MYC transcription.
AB  - The nuclease hypersensitivity element III(1) upstream of the P1 promoter of c-MYC
      controls 85-90% of the transcriptional activation of this gene. We have
      demonstrated that the purine-rich strand of the DNA in this region can form two
      different intramolecular G-quadruplex structures, only one of which seems to be
      biologically relevant. This biologically relevant structure is the kinetically
      favored chair-form G-quadruplex, which is destabilized when mutated with a single
      G --> A transition, resulting in a 3-fold increase in basal transcriptional
      activity of the c-MYC promoter. The cationic porphyrin TMPyP4, which has been
      shown to stabilize this G-quadruplex structure, is able to suppress further c-MYC
      transcriptional activation. These results provide compelling evidence that a
      specific G-quadruplex structure formed in the c-MYC promoter region functions as
      a transcriptional repressor element. Furthermore, we establish the principle that
      c-MYC transcription can be controlled by ligand-mediated G-quadruplex
      stabilization.

PMID- 12195019
TI  - PPAR alpha is necessary for the lipopenic action of hyperleptinemia on white
      adipose and liver tissue.
AB  - Adenovirus-induced hyperleptinemia causes rapid disappearance of body fat in
      normal rats, presumably by up-regulating fatty acid oxidation within white
      adipocytes. To determine the role of peroxisomal proliferation-activated receptor
      (PPAR)alpha expression, which was increased during the rapid loss of fat, we
      infused adenovirus-leptin into PPAR alpha(-/-) and PPAR alpha(+/+) mice. Despite
      similar degrees of hyperleptinemia and reduction in food intake, epididymal fat
      pad weight declined 55% in wild-type but only 6% in PPAR alpha(-/-) mice; liver
      triacylglycerol fell 39% in the wild-type group but was unchanged in PPAR(-/-)
      mice. Carnitine palmitoyl transferase-1 mRNA rose 52% in the wild-type mice but
      did not increase in PPAR alpha(-/-) mice. PPAR gamma coactivator-1 alpha rose 3
      fold in the fat and 46% in the liver of wild-type mice but was unchanged in PPAR
      alpha(-/-) mice. Although AMP-activated protein kinase could not be implicated in
      the lipopenic actions of hyperleptinemia, acetyl CoA carboxylase protein was
      reduced in the liver of wild-type but not in PPAR alpha(-/-) mice. Thus, in PPAR
      alpha(-/-) mice, up-regulation of carnitine palmitoyl transferase-1 mRNA in fat,
      down-regulation of acetyl CoA carboxylase in liver, and up-regulation of PPAR
      gamma coactivator-1 alpha mRNA in both tissues are abolished, as is the reduction
      in their triacylglycerol content.

PMID- 12195021
TI  - SAGE Genie: a suite with panoramic view of gene expression.

PMID- 12195022
TI  - A new name in thrombosis, ADAMTS13.

PMID- 12195020
TI  - Epstein-Barr virus EBNA2 blocks Nur77- mediated apoptosis.
AB  - Epstein-Barr virus infection in vitro immortalizes primary B cells. EBNA2 is an
      Epstein-Barr virus-encoded transcriptional transactivator that mimics the effects
      of activated Notch signaling and is essential for this proliferative response. An
      assay using Sindbis virus (SV) as a cell death inducer revealed that, like Notch,
      EBNA2 also has antiapoptotic activity. We show that Nur77 is a mediator of SV
      induced cell death and that EBNA2 antiapoptotic activity results from interaction
      with Nur77. EBNA2 colocalized with Nur77 in transfected cells and coprecipitated
      with Nur77 in IB4 B cells. EBNA2 binds to Nur77 through sequences in the EBNA2
      amino acid 123-147 conserved domain and an EBNA2 mutant unable to bind Nur77 also
      lost the ability to protect cells from SV-induced apoptosis. EBNA2 exerted its
      antideath function by retaining Nur77 in the nucleus and preventing Nur77 from
      targeting mitochondria in response to apoptotic stimuli. Thus, targeting of Nur77
      can be added to the list of strategies used by viruses to counter apoptosis.

PMID- 12195023
TI  - RNA traffics information systemically in plants.

PMID- 12195024
TI  - Plant proteomics: BLASTing out of a MudPIT.

PMID- 12195025
TI  - An intracellular block to primate lentivirus replication.

PMID- 12195026
TI  - Continued evolutionary surprises among dinoflagellates.

PMID- 12195027
TI  - Signal transduction--directed cancer treatments.
AB  - The pathogenic mechanisms giving rise to cancer frequently involve altered signal
      transduction pathways. Therefore therapeutic agents that directly address signal
      transduction molecules are being explored as cancer treatments. Inhibitors of
      protein tyrosine and threonine kinases including STI-571, ZD-1839, OSI-774, and
      flavopiridol are ATP-site antagonists that have completed initial phase I and
      phase II evaluations. Herceptin and C225 are monoclonal antibodies also directed
      against signaling targets. Numerous other kinase antagonists are in clinical
      evaluation, including UCN-01 and PD184352. Alternative strategies to downmodulate
      kinase-driven signaling include 17-allyl-amino-17-demethoxygeldanamycin and
      rapamycin derivatives, and phospholipase-directed signaling may be modulated by
      alkylphospholipids. Farnesyltransferase inhibitors were originally developed as
      inhibitors of ras-driven signals but may have activity by affecting other or
      additional targets. Signal transduction will remain a fertile basis for
      suggesting cancer treatments of the future, the evaluation of which should
      include monitoring effects of the drugs on their intended target signaling
      molecules in preclinical and early clinical studies.

PMID- 12195028
TI  - Hormesis: the dose-response revolution.
AB  - Hormesis, a dose-response relationship phenomenon characterized by low-dose
      stimulation and high-dose inhibition, has been frequently observed in properly
      designed studies and is broadly generalizable as being independent of
      chemical/physical agent, biological model, and endpoint measured. This under
      recognized and -appreciated concept has the potential to profoundly change
      toxicology and its related disciplines with respect to study design, animal model
      selection, endpoint selection, risk assessment methods, and numerous other
      aspects, including chemotherapeutics. This article indicates that as a result of
      hormesis, fundamental changes in the concept and conduct of toxicology and risk
      assessment should be made, including (a) the definition of toxicology, (b) the
      process of hazard (e.g., including study design, selection of biological model,
      dose number and distribution, endpoint measured, and temporal sequence) and risk
      assessment [e.g., concept of NOAEL (no observed adverse effect level), low dose
      modeling, recognition of beneficial as well as harmful responses] for all agents,
      and (c) the harmonization of cancer and noncancer risk assessment.

PMID- 12195029
TI  - The Wilhelmine E. Key 2001 Invitational Lecture. Estimation of divergence times
      for a few mammalian and several primate species.
AB  - Statistical methods for estimating divergence times by using multiprotein gamma
      distances are discussed. When a large number of proteins are used, even a small
      degree of deviation from the molecular clock hypothesis can be detected. In this
      case, one may use the stem-lineage method for estimating divergence times.
      However, the estimates obtained by this method are often similar to those
      obtained by the linearized tree method. Application of these methods to a dataset
      of 104 proteins from several vertebrate species indicated that the divergence
      times between humans and mice and between mice and rats are about 96 and 33
      million years (MY) ago, respectively. These estimates were obtained by assuming
      that birds and mammals diverged 310 MY ago. Similarly application of the methods
      to the protein sequence data from primate species indicated that the human
      lineage separated from the chimpanzee, gorilla, Old World monkeys, and New World
      monkeys about 6.0, 7.0, 23.0, and 33.0 MY ago, respectively. In this case the use
      of two calibration points, that is, the divergence time (13 MY ago) between
      humans and orangutans and between primates and artiodactyls (90 MY ago) gave
      essentially the same estimates.

PMID- 12195030
TI  - Sexual reproduction in the white pine weevil (Pissodes strobi [Peck] [Coleoptera:
      Curculionidae]): implications for population genetic diversity.
AB  - Controlled mating experiments in the white pine weevil (Pissodes strobi [Peck])
      indicated that female weevils either stored sperm or fertilized eggs from one
      season to the next, and were able to colonize Sitka spruce (Picea sitchensis
      [Bong.] Carr.) trees without additional mating events. This was interpreted as
      being beneficial for the insect, in that population establishment in a new
      habitat could be initiated by dispersing previously mated females without
      participation of the male. This makes colonization and population/outbreak
      development more likely as it reduces the need for mate searching in the second
      season. Paternity identification, based on microsatellite molecular markers,
      established that the progeny produced in year 2 by females mated only in year 1,
      were often fathered by more than one male. Multiple paternity, coupled with a
      lack of parthenogenesis, which was also demonstrated herein, may help to account
      for the high degree of genetic diversity evidenced in this species.

PMID- 12195031
TI  - Genetic control of the honey bee (Apis mellifera) dance language: segregating
      dance forms in a backcrossed colony.
AB  - We studied the genetic control of the dance dialects that exist in the different
      subspecies of honey bees (Apis mellifera) by observing the variation in dance
      form observed in a backcross between two lines that showed widely different dance
      dialects. To do this we generated the reciprocal of the cross performed by
      Rinderer and Beaman (1995), thus producing phenotypic segregation of dance forms
      within a single colony rather than between colonies. Our results are consistent
      with Rinderer and Beaman (1995) in that inheritance of the transition point from
      round dancing --> waggle dancing is consistent with control by a single locus
      with more than one allele. That is, we found one dance type to be dominant in the
      F(1), and observed a 1:1 segregation of dance in a backcross involving the F(1)
      and the recessive parent. However, we found some minor differences in dance
      dialect inheritance, with the most significant being an apparent reversal of
      dominance between our cross (for us "black" is the dominant dialect) and that of
      Rinderer and Beaman (1995) (they report "yellow" to be the dominant dialect). We
      also found that our black bees do not perform a distinct sickle dance, whereas
      the black bees used by Rinderer and Beaman (1995) did perform such a dance.
      However, our difference in dominance need not contradict the results of Rinderer
      and Beaman (1995), as there is no evidence that body color and dominance for
      dance dialect are linked.

PMID- 12195032
TI  - Inheritance of organelle DNA sequences in a citrus-poncirus intergeneric cross.
AB  - Many land plants deviate from the maternal pattern of organelle inheritance. In
      this study, heterologous mitochondrial and chloroplast probes were used to
      investigate the inheritance of organelle genomes in the progeny of an
      intergeneric cross. The seed parent was LB 1-18 (a hybrid of Citrus reticulata
      Blanco cv. Clementine x C. paradisi Macf. cv. Duncan) and the pollen parent was
      the cross-compatible species Poncirus trifoliata (L.) Raf. All 26 progeny
      examined exhibited maternal inheritance of plastid petA and petD loci. However,
      17 of the 26 progeny exhibited an apparent biparental inheritance of
      mitochondrial atpA, cob, coxII, and coxIII restriction fragment length
      polymorphisms (RFLPs) and maternal inheritance of mitochondrial rrn26 and coxI
      RFLPs. The remaining nine progeny inherited only maternal mitochondrial DNA
      (mtDNA) configurations. Investigations of plant mitochondrial genome inheritance
      are complicated by the multipartite structure of this genome, nuclear gene
      control over mitochondrial genome organization, and transfer of mitochondrial
      sequences to the nucleus. In this study, paternal mtDNA configurations were not
      detected in purified mtDNA of progeny plants, but were present in progeny DNA
      preparations enriched for nuclear genome sequences. MtDNA sequences in the
      nuclear genome therefore produced an inheritance pattern that mimics biparental
      inheritance of mtDNA.

PMID- 12195033
TI  - Complementary action of two independent dominant genes in Columbia soybean for
      resistance to Soybean mosaic virus.
AB  - A stem-tip necrosis disease was observed in the soybean [Glycine max (L.) Merr.]
      cultivar Columbia and its derivative OX686 when infected with a necrosis-causing
      strain of Soybean mosaic virus (SMV) in Canada. A dominant gene named Rsv3 was
      found in OX686 for the necrotic reaction. In the present research we have found
      that Columbia is resistant to all known SMV strains G1-G7, except G4. Genetic
      studies were conducted to investigate the inheritance of resistance in Columbia
      and interactions of resistance gene(s) with SMV strains. Columbia was crossed
      with a susceptible cultivar, Lee 68, and with resistant lines PI96983, Ogden, and
      LR1, each possessing a resistance gene at the Rsv1 locus. F(1) individuals, F(2)
      populations, and F(2:3) lines from these crosses were inoculated with G7 or G1 in
      the greenhouse. Our inheritance data confirmed the presence of two independent
      dominant genes for SMV resistance in Columbia. Results from allelism tests
      further demonstrate that the two genes (referred to as R3 and R4 in this article)
      in Columbia were independent of the Rsv1 locus. R3 appears to be the same gene
      previously reported as Rsv3 in OX686, which was derived from Columbia. The R3
      gene confers resistance to G7, but necrosis to G1. The other gene, R4, conditions
      resistance to G1 and G7 at the early seedling stage and then a delayed mild
      mosaic reaction (late susceptible) 3 weeks later. Plants carrying both the R3 and
      R4 genes were completely resistant to both G1 and G7, indicating that the two
      genes interact in a complementary fashion. Plants heterozygous for R3 or R4
      exhibited systemic necrosis or late susceptibility, suggesting that the
      resistance is allele dosage dependent. The R4 gene appeared epistatic to R3 since
      it masked expression of necrosis associated with the response of R3. The
      complementary interaction of two resistance genes, as exhibited in Columbia, can
      be useful in development of soybean cultivars with multiple and durable
      resistance to SMV.

PMID- 12195034
TI  - Occurrence and cytological mechanism of 2n pollen formation in a tetraploid
      accession of Ipomoea batatas (sweet potato).
AB  - We evaluated a 4x accession of Ipomoea batatas (L.) Lam. and four 2x accessions
      of Ipomoea triloba for 2n pollen production. Approximately 90% of the genotypes
      of accession 81.2 (I. batatas, 4x) produced 2n pollen with different frequencies.
      In contrast, none of the genotypes of I. triloba produced 2n pollen. The diameter
      of the 2n pollen was approximately 30% ((3) sqrt 2) larger than that of the n
      pollen, making it easy to identify, measure, and quantify. The correlation (r =
      0.93**) between the frequency of giant pollen and the frequency of dyads and
      triads was highly significant, strongly suggesting that the giant pollen grains
      were 2n pollen. The 2n pollen producers presented either a parallel or tripolar
      spindle arrangement (Y shaped) at anaphase II instead of the normal 60 degrees
      crossed spindle orientation. These two abnormal spindle configurations produced
      dyads and triads, with different frequencies (13-67%), instead of tetrads.
      Occasionally a metaphase II spindle variation was found with a single fused
      spindle, which also forms a dyad. The correlation (r = 0.89**) between the
      frequency of 2n pollen and the frequency of parallel, fused, and tripolar spindle
      arrangements was also highly significant, suggesting that these abnormal spindle
      configurations are involved in the production of 2n pollen in I. batatas. When we
      evaluated the efficiency of 2n pollen in polyploidization using 4x x 4x (2n)
      crosses, all progenies were 4x, suggesting the existence of barriers to
      crossability between 4x genotypes and their 2n pollen-producer counterparts.

PMID- 12195035
TI  - Allozyme diversity and genetic structure of the leafy cactus (Pereskia guamacho
      [Cactaceae]).
AB  - We examined levels of genetic variation and genetic structure in the leafy cactus
      (Pereskia guamacho) in arid and semiarid zones in Venezuela. We surveyed genetic
      diversity within 17 populations using 19 allozyme loci. Genetic diversity was
      relatively high at both the species (P(s) = 89%, A(s) = 3.26, AP(s) = 3.53, H(es)
      = 0.24) and population (P(p) = 63%, A(p) = 1.90, AP(p) = 2.42, H(ep) = 0.20)
      levels. A significant deficit of heterozygote individuals was detected within
      populations in the Paraguana Peninsula region (F(IS) = 0.301). Relatively low
      levels of population differentiation were detected at macrogeographic (G(ST) =
      0.112) and regional levels (G(ST) = 0.044 for peninsula region and G(ST) = 0.074
      for mainland region), suggesting substantial genetic exchange among populations;
      however, gene flow in this species seems to be regulated by the distance among
      populations. Overall, estimates of genetic diversity found in P. guamacho are
      concordant with the pattern observed for other cacti surveyed, namely high levels
      of polymorphism and genetic diversity with one common allele and several rare
      alleles per locus. Differences in gene dispersal systems between this species and
      other cacti studied were not reflected in the patterns of genetic diversity
      observed. The concentration of the highest estimates of genetic variation in
      northwestern Venezuela suggests a potential reservoir of plant genetic diversity
      within xerophilous ecosystems in northern South America.

PMID- 12195036
TI  - Evidence for the lack of mismatch-repair directed antirecombination during mouse
      meiosis.
AB  - Meiotic recombination was studied in DNA mismatch repair (MMR)-deficient mice
      using a strain carrying a Pms2 knockout mutation. Using single-sperm typing,
      recombination was analyzed over five intervals on four chromosomes in four Pms2 
      /- animals. A total of 1936 meioses were studied and compared to 1848 meioses
      from three Pms2 +/+ controls. A smaller study was carried out on a single
      interval in each of two chromosomes in an MMR-deficient mouse homozygous for the
      Msh2 knockout mutation. A total of 792 meioses were examined in the Msh2 -/- and
      880 meioses in the Msh2 +/+ animal. Recombination fractions were not
      significantly different in either of the MMR-deficient mouse strains when
      compared to MMR-proficient controls. Our results appear to conflict with mouse
      embryonic stem (ES) cell gene-targeting experiments where MMR plays a major role
      in determining the efficiency of homologous recombination between nonidentical
      sequences. A number of possibilities could explain the apparent lack of a
      significant effect on meiosis.

PMID- 12195037
TI  - Different levels of human intervention in domestic rabbits: effects on genetic
      diversity.
AB  - The effects of human interaction on domestic rabbits were evaluated through the
      analysis of animals (up to 267) belonging to fancy breeds (22), a commercial
      breed (1), and selected strains (2). Microsatellite loci and mtDNA polymorphism
      revealed that the genetic pool of domestic rabbits studied only originated from
      that available in France. The good conservation of the original diversity was
      probably ensured through the multiplicity of samplings from wild populations.
      Selected strains, because of the breeding strategy, keep a fairly high level of
      diversity compared to other breeds.

PMID- 12195038
TI  - A blond coat color variation in meadow vole (Microtus pennsylvanicus).
AB  - Color mutations occur frequently among rodents. Here we describe a blond coat
      color mutation in the meadow vole (Microtus pennsylvanicus) that arose in a
      captive breeding colony established from wild-caught animals from southern
      Illinois. The blond coat coloration results from changes in the color and
      distribution of pigments in the hair. The mutation is monogenic autosomal
      recessive.

PMID- 12195039
TI  - The Charles River "hairless" rat mutation maps to chromosome 1: allelic with
      fuzzy and a likely orthologue of mouse frizzy.
AB  - Recent evidence has indicated that the recessive mutation affecting hypotrichosis
      in the Charles River (CR) "hairless" rat does not involve the hairless gene (hr)
      on rat chromosome 15. To determine if this mutation might be allelic (or
      orthologous) with any other previously mapped hypotrichosis-generating mutation
      in mammals, we have produced a panel of backcross rats segregating for the CR
      hairless rat mutation as well as numerous other markers from throughout the rat
      genome. Analysis of this panel has located the CR hairless rat's hypotrichosis
      generating mutation on chromosome 1, near Myl2, where only the fuzzy mutation in
      rat (fz) and the frizzy mutation in mouse (fr) have been previously localized.
      Intercrossing fz/fz and CR hairless rats produced hybrid offspring with abnormal
      hair, showing that these two rat mutations are allelic. We suggest that the CR
      hairless rat mutation and fuzzy be renamed frizzy-Charles River (fr(CR)) and
      frizzy-Harlan (fr(H)), respectively, to reflect their likely orthology with the
      mouse fr mutation.

PMID- 12195040
TI  - Optimal positioning of markers to control genetic background in marker-assisted
      backcrossing.
AB  - Molecular markers are commonly used in backcross breeding programs in plants. As
      genetic maps contain more and more markers, it is of interest to determine which
      markers are to be used for selection. Here we describe how one can compute an
      optimal positioning of markers resulting in a maximization of the expected
      proportion of recipient genome. This criterion allows us to take selection into
      account and to produce relevant results regarding the final efficiency of
      background selection in backcross programs.

PMID- 12195041
TI  - Polymorphic microsatellites in Antirrhinum (Scrophulariaceae), a genus with low
      levels of nuclear sequence variability.
AB  - In Antirrhinum, reproductive systems range from self-compatible to self
      incompatible, but the actual outcrossing rates of self-compatible populations are
      not known. Thus the extent to which levels of variability and inbreeding differ
      among Antirrhinum populations is not known. In order to address this issue we
      isolated nine Antirrhinum nuclear microsatellite loci. In contrast to several
      nuclear genes that show low levels of sequence variation, six of the
      microsatellite loci indicate high levels of variability within and between
      Antirrhinum species. The highly self-compatible Antirrhinum majus ssp.
      cirrhigerum population has high levels of variability and no significant
      deviation from Hardy-Weinberg equilibrium, suggesting substantial rates of
      outcrossing.

PMID- 12195042
TI  - Simple sequence repeat (SSR) markers linked to the Ligon lintless (Li(1)) mutant
      in cotton.
AB  - Ligon lintless (Li(1)) is a monogenic, dominant mutant in cotton, whose
      expression results in extreme reductions in fiber length on mature seed. The
      objectives of this research were to compare fiber initiation between the Li(1)
      mutant and TM-1 to reveal the fiber initiation differences between normal and
      mutant phenotypes, to develop a linkage map of simple sequence repeat (SSR)
      markers with the Li(1) locus, and to identify the chromosomal location of the
      Li(1) locus. Comparative scanning electron microscopy studies of fiber
      development in a normal TM-1 genotype and the near-isogenic Li(1) mutant at 1 and
      3 days postanthesis revealed little differences between the two during early
      stages of development, suggesting that Li(1) gene expression occurs later,
      probably during the elongation phase. Thirty-eight SSR loci were found to be
      polymorphic between TM-1 and Li(1) and were used for mapping in an F(2)
      population. Twenty-two SSR loci, along with Li(1), were located on eight linkage
      groups, covering a total genetic distance of 218.3 cM. Analysis of individual
      monosomic and monotelodisomic plants indicated that two SSR loci (MP4030 and
      MP673) from the Li(1) linkage group were located on chromosome 22.

PMID- 12195043
TI  - FITMAPS and SHOWMAP: two programs for graphical comparison and plotting of
      genetic maps.

PMID- 12195044
TI  - MDM: a program to compute fully informative genotype frequencies in complex
      breeding schemes.

PMID- 12195046
TI  - Epidemiology and clinical aspects on hepatitis C.
AB  - Hepatitis C virus (HCV) infects an estimated 170 million persons worldwide, and 2
      million persons in Japan. HCV is a major cause of chronic liver diseases,
      especially hepatocarcinogenesis, and the number of patients with HCV-related
      hepatocellular carcinoma (HCC) is increasing worldwide as well as in Japan. Most
      patients with acute hepatitis C develop chronic hepatitis. Spontaneous
      disappearance of HCV in patients with type C chronic liver disease is uncommon,
      and it tends to progress to further advanced and more severe liver disease,
      ultimately to HCC over a period of 30 years in most cases. Chronic liver disease
      due to HCV infection is commonly associated with extrahepatic manifestation, for
      example cryoglobulinemia. Antiviral treatment for HCV infection with interferon
      alone during 24 weeks was associated with a low rate (less than 10%) of sustained
      virologic response (SVR), especially in patients infected with HCV genotype 1b
      and high HCV RNA concentration. However, combination therapy of interferon and
      ribavirin raises the SVR rate. More recently, pegylated interferon used for
      treatment of chronic hepatitis C resulted in a high SVR rate. These modalities of
      antiviral treatment will reduce HCC occurrence. So far, there is no HCV vaccine
      in spite of many efforts.

PMID- 12195047
TI  - Effect of anti-mosquito hemolymph antibodies on fecundity and on the infectivity
      of malarial parasite Plasmodium vivax to Anopheles stephensi (Diptera:Insecta).
AB  - Rabbit antibodies to hemolymph antigens (102.5, 101, 100, 96, 88, 80, 64, 55, 43,
      29, and 23 kDa) of Anopheles stephensi reduced fecundity as well as viability in
      An. stephensi. However, ingestion of these antibodies was not associated with a
      marked effect on the engorgement of mosquitoes but egg laying was significantly
      delayed. Antisera raised against hemolymph proteins were also used to identify
      cross reactive antigens/epitopes present in other tissues by Western blotting, as
      well as by in vivo ELISA. In addition, a significant reduction in oocyst
      development was also observed in An. stephensi mosquitoes that ingested anti
      hemolymph antibodies along with Plasmodium vivax. The results confirmed the
      feasibility of targeting mosquito antigens as a novel anti-mosquito strategy, as
      well as confirmed the usefulness of such antigens for the development of a
      transmission-blocking vaccine.

PMID- 12195048
TI  - Prevalence of intestinal parasitic pathogens in HIV-seropositive individuals in
      Northern India.
AB  - To assess the prevalence of intestinal parasitic infections in human
      immunodeficiency virus (HIV)-seropositive subjects, fecal samples were collected
      from 120 HIV-seropositive patients and were analyzed for various intestinal
      parasites. Thirty-six patients (30%) were found to harbor an intestinal parasite.
      Cryptosporidium parvum was the most common (10.8%), followed by Giardia lamblia
      (8.3%). Cyclospora cayetanensis and Blastocystis hominis each were detected in
      3.3% of the patients, while Isospora belli and Enterocytozoon bieneusi were each
      detected in 2.5% of the patients. The other parasites observed were Entamoeba
      histolytica/E. dispar in two cases and hookworm ova in one patient. Of the 36
      patients who tested positive for intestinal parasites, 27 (75%) had diarrhea. The
      most common parasite, which was associated with diarrhea, was C. parvum. The
      present study highlights the importance of testing for intestinal parasites in
      patients who are HIV-positive, and emphasizes the necessity of increasing
      awareness among clinicians regarding the occurrence of these parasites in this
      population.

PMID- 12195049
TI  - Recurrent herpes simplex virus type 2 meningitis: a case report of Mollaret's
      meningitis.
AB  - It is well known that herpes simplex virus (HSV) type 2 produces acute
      meningitis, while HSV type 2 rarely causes recurrent meningitis (Mollaret's
      meningitis). We report the history of a 40-year-old patient with recurrent HSV
      type 2 meningitis (Mollaret's meningitis). The patient had seven episodes of
      meningeal symptoms within a 7-year period. In the seventh episode, HSV type 2 DNA
      was confirmed by nested polymerase chain reaction (PCR) with the cerebrospinal
      fluid (CSF). A real-time quantitative PCR study of the first CSF sample detected
      2,000 copies of the HSV genome, which rapidly disappeared following treatment
      with acyclovir. The present case may be the first case of HSV type 2 Mollaret's
      meningitis to be documented in Japan. In our case, HSV serum antibody titers were
      at low levels during the whole course of the disease. The possible
      pathophysiology of this case is discussed.

PMID- 12195050
TI  - Molecular epidemiology of group A streptococci T serotype 1.

PMID- 12195051
TI  - An outbreak of enterohemorrhagic Escherichia coli O157 caused by ingestion of
      contaminated beef at grilled meat-restaurant chain stores in the Kinki District
      in Japan: epidemiological analysis by pulsed-field gel electrophoresis.

PMID- 12195052
TI  - Molecular epidemiological surveillance of methicillin-resistant Staphylococcus
      aureus in a Hiroshima community hospital in 2002.

PMID- 12195053
TI  - Eradication of poliomyelitis in Ethiopia: virological and acute flaccid paralysis
      surveillance.

PMID- 12195054
TI  - Evaluation of the school health surveillance system for influenza, Tokyo, 1999
      2000.

PMID- 12195055
TI  - Amplification of irrelevant sequence from Bacillus subtilis using a primer set
      designed for detection of the pag gene of Bacillus anthracis.

PMID- 12195057
TI  - A prospective randomized comparison between the cloward procedure and a carbon
      fiber cage in the cervical spine: a clinical and radiologic study.
AB  - STUDY DESIGN: A prospective randomized study was conducted. OBJECTIVE: To
      determine whether the use of a cervical carbon fiber intervertebral fusion cage
      improves the outcome of anterior cervical decompression and fusion, as compared
      with the Cloward procedure using autograft. SUMMARY OF BACKGROUND DATA: Despite
      the theoretical advantages of using intervertebral cages, including reduced donor
      site morbidity and prevention of graft collapse, an improved clinical outcome has
      not yet been documented. METHODS: For this study, 103 patients were randomized to
      anterior cervical decompression and fusion with a carbon fiber intervertebral
      fusion cage (n = 52) or the Cloward procedure (n = 51). An independent observer
      quantified pain and functional disability. Fusion rate, segmental kyphosis, and
      disc height were assessed by radiographs. RESULTS: During a mean follow-up period
      of 36 months (range, 24-72 months) for 89 patients (86%), the pain and disability
      were similar for both treatments. Postoperative donor site pain was significantly
      less in the carbon fiber intervertebral fusion cage group. The fusion rate was
      86% in the Cloward procedure group and 62% in the carbon fiber intervertebral
      fusion cage group (P < 0.05). In the latter group, patients with pseudarthrosis
      reported more severe pain than fused patients (51 and 33 visual analog scores,
      respectively), but the difference was not significant. The segmental kyphosis was
      less and the disc height increased in the carbon fiber intervertebral fusion cage
      group, as compared with the Cloward procedure group. Disc height was not
      correlated with outcome. Segmental kyphosis showed a weak (r = -0.3) but
      significant (P < 0.05) correlation with improvement of the Cervical Spine
      Functional Score, but not with other outcome variables. CONCLUSIONS: Except for
      reduced donor site pain, the clinical outcome for the carbon fiber intervertebral
      fusion cage is the same as for the Cloward procedure. Use of the cage results in
      a more lordotic alignment and an increased disc height, but in a higher
      pseudarthrosis rate than use of the Cloward procedure.

PMID- 12195058
TI  - The effect of McKenzie therapy as compared with that of intensive strengthening
      training for the treatment of patients with subacute or chronic low back pain: A
      randomized controlled trial.
AB  - STUDY DESIGN: A randomized controlled comparative trial with an 8-month follow-up
      period was conducted. OBJECTIVE: To compare the effect of the McKenzie treatment
      method with that of intensive dynamic strengthening training in patients with
      subacute or chronic low back pain. SUMMARY OF BACKGROUND DATA: Randomized studies
      indicate that the efficacy of the McKenzie method in the treatment of patients
      with acute or subacute low back pain is debatable. Currently, no randomized
      studies examining the effects of this method for patients with chronic low back
      pain have been published. METHODS: For this study, 260 consecutive patients with
      low back pain and at least 8 weeks duration of symptoms (85% of the patients had
      more than 3 months duration of symptoms) were randomized into two groups: Group A
      was treated with the McKenzie method (n = 132), and Group B was treated with
      intensive dynamic strengthening training (n = 128). The treatment period for both
      groups was 8 weeks at an outpatient clinic, followed by 2 months of self-training
      at home. Treatment results were recorded at the end of the treatment period at
      the clinic, then 2 and 8 months after. In both groups, 30% of the patients were
      lost to follow-up evaluation. An intention-to-treat analysis of the main effect
      variables, disability, and pain was performed for all the patients included in
      the study. A supplementary analysis of the 180 patients who completed the full
      treatment program also was undertaken. RESULTS: Intention-to-treat analysis
      showed a tendency toward a difference in reduction of disability in favor of the
      McKenzie group at the 2-month follow-up assessment (P = 0.04), but no differences
      at the end of treatment and at the 8-month follow-up evaluation. No differences
      in reduction of pain were observed at any time between the groups. The
      supplementary analysis of the patients who had completed the full intervention
      showed a tendency toward a difference in favor of the McKenzie method in
      reduction of pain at the end of treatment (P = 0.02). This difference reached
      statistical significance at the 2-month follow-up assessment (P = 0.01), but no
      difference was found after 8 months. The supplementary analysis showed no
      differences between the groups with regard to reduction of disability.
      CONCLUSION: The McKenzie method and intensive dynamic strengthening training seem
      to be equally effective in the treatment of patients with subacute or chronic low
      back pain.

PMID- 12195059
TI  - Point of view.

PMID- 12195060
TI  - IGF-I and TGF-beta1 application by a poly-(D,L-lactide)-coated cage promotes
      intervertebral bone matrix formation in the sheep cervical spine.
AB  - STUDY DESIGN: A sheep cervical spine interbody fusion model was used to determine
      the effect of combined insulin-like growth factor-I (IGF-I) and transforming
      growth factor-beta-1 (TGF-beta1) applied by a poly-(D,L-lactide) (PDLLA)-coated
      cage. OBJECTIVES: The purpose of this study was to determine the effect of a new
      PDLLA carrier system, and to evaluate the effect of combined IGF-I and TGF-beta1
      application in a sheep cervical spine model. SUMMARY AND BACKGROUND DATA: Growth
      factors such as bone morphogenic protein-2 have been shown to promote spine
      fusion and to overcome the disadvantages of an autologous bone graft. The optimum
      growth factor for promoting spinal fusion and the optimum method for delivering
      such growth factors are still a matter of discussion. METHOD: In this study, 32
      sheep underwent C3-C4 discectomy and fusion: Group 1 (autologous tricortical
      iliac crest bone graft; n = 8), Group 2 (titanium cage; n = 8), Group 3 (titanium
      cage coated with a PDLLA carrier; n = 8), and Group 4 (titanium cage coated with
      a PDLLA carrier including IGF-I [5% w/w] and TGF-beta1 [1% w/w; n = 8). Blood
      samples, body weight, and body temperature were analyzed. Radiographic scans were
      performed before and after surgery, then at 1, 2, 4, 8, and 12 weeks,
      respectively. At the same time points, the disc space height, intervertebral
      angle, and lordosis angle were measured. After 12 weeks, the animals were killed,
      and fusion sites were evaluated using functional radiographic views of the
      animals in flexion and extension. Quantitative computed tomographic scans were
      performed to assess bone mineral density, bone mineral content, and bony callus
      volume. Biomechanical testing of the motion segment C3-C4 was performed in
      flexion, extension, axial rotation, and lateral bending. The stiffness, range of
      motion, neutral zone, and elastic zone were determined. Histomorphologic and
      histomorphometric analysis was performed, and polychrome sequential labeling was
      used to determine the time frame of new bone formation. RESULTS: There were no
      differences between the groups in terms of blood counts, body weight, and
      temperature. Over a 12-week period, cage Groups 2 to 4 showed significantly
      higher values for the intervertebral angle than for the bone graft. Functional
      radiographic assessment showed significantly lower residual flexion-extension
      movement in Group 4 than in any other group. The PDLLA-coated cages with IGF-I
      and TGF-beta1 showed significantly higher values for bone mineral density, bone
      mineral content, and bony callus volume. The average stiffness in rotation and
      bending was significantly higher, and the range of motion, neutral zone, and
      elastic zone in rotation were significantly lower in Group 4 than in any other
      group. Although only one animal in Group 4 demonstrated solid bony fusion after
      12 weeks, histomorphometric evaluation showed a more progressed bone matrix
      formation in the group that had PDLLA-coated cages with IGF-I and TGF-beta1 than
      in any other group. Polychrome sequential labeling showed accelerated
      intervertebral bone matrix formation in Group 4. CONCLUSIONS: The findings showed
      that PDLLA coating of cervical spine interbody fusion cages as a delivery system
      for growth factors was effective. Although IGF-I and TGF-beta1 application by a
      PDLLA-coated interbody cage was not able to achieve solid bony fusion during the
      12-week follow-up period, these growth factors significantly increased the
      results of interbody bone matrix formation. Additional longer-term studies are
      required to determine whether combined IGF-I and TGF-beta1 application leads to a
      successful spinal fusion.

PMID- 12195061
TI  - Point of view.

PMID- 12195063
TI  - Recovery of neurologic function after spinal cord injury in Israel.
AB  - STUDY DESIGN: A retrospective cohort study was conducted. OBJECTIVE: To assess
      neurologic recovery and the manner in which it is affected by the severity of the
      neurologic damage after spinal cord injury. SUMMARY OF BACKGROUND DATA: Studies
      from various countries, but not from Israel, have shown considerable potential
      for recovery of the damaged human spinal cord. METHODS: The study sample included
      250 patients with a traumatic spinal cord lesion treated between 1962 and 1992 at
      the major referral hospital for rehabilitation in Israel. Demographic and
      clinical data were collected from the hospital charts. The degree of neurologic
      recovery in each patient was determined by comparing the Frankel grade of
      neurologic deficit at first admission for rehabilitation with the grade at
      discharge from that hospitalization. RESULTS: There was median delay of 36 days
      between injury and admission for rehabilitation. During rehabilitation, full or
      substantial neurologic recovery (upgrade to Frankel Grade D or E) occurred in 27%
      of all the patients who were Grade A, B, or C on admission, and in 54% of those
      who were Grade C. The neurologic recovery was negatively associated with severity
      of the neurologic deficit. CONCLUSIONS: The outcome findings are similar to those
      reported from spinal rehabilitation units in other countries. The study is a
      further demonstration of the considerable potential for neurologic recovery after
      spinal cord injury, when posttraumatic or postsurgical management is focused on
      prevention of complications and maximal use of functional ability.

PMID- 12195062
TI  - Posterior atlantoaxial fixation: biomechanical in vitro comparison of six
      different techniques.
AB  - STUDY DESIGN: Six different techniques for atlantoaxial fixation were
      biomechanically compared in vitro by nondestructive testing. OBJECTIVE: To
      evaluate the immediate three-dimensional stability of a new atlas claw combined
      with transarticular screws and alternative techniques for transarticular screw
      fixation in comparison with established techniques. SUMMARY OF BACKGROUND DATA:
      Posterior transarticular screw fixation in combination with wire-bone graft
      constructs is frequently used for C1-C2 fixation. Sublaminar wire passage carries
      the potential risk of neurologic complication. Transarticular screw fixation is
      technically demanding and, for anatomic reasons, not always feasible. METHODS:
      Six human cervical specimens were loaded nondestructively with pure moments, and
      unconstrained motion at C1-C2 was measured. The six specimens were instrumented
      with each of the following fixation techniques: Gallie fixation, transarticular
      screws and Gallie fixation, transarticular screws, transarticular screws and a
      new atlas claw, isthmic screws in the axis and the atlas claw, and lateral mass
      screws in the atlas and isthmic screws in the axis connected with rods. RESULTS:
      The transarticular screws restricted lateral bending and axial rotation best. The
      three-point fixations (transarticular + Gallie and transarticular + claw)
      additionally restricted flexion-extension, with lowest values for transarticular
      screws and the atlas claw. The alternative techniques were not as stable as the
      three-point fixations, but more stable than the Gallie fixation. CONCLUSIONS:
      Biomechanically, the three-point fixation with transarticular screws and the
      atlas claw provides a rigid internal fixation that is not dependent on bone graft
      and sublaminar wiring. In cases wherein transarticular screws are not feasible,
      the isthmic screws and claw or the lateral mass screws and isthmic screws are
      biomechanical alternatives with less immediate stability.

PMID- 12195064
TI  - The cochrane review of advice to stay active as a single treatment for low back
      pain and sciatica.
AB  - STUDY DESIGN: A systematic review was conducted within the Cochrane Collaboration
      Back Review Group. OBJECTIVES: To assess the effects of advice to stay active as
      a single treatment for patients with acute low back pain or sciatica. SUMMARY OF
      BACKGROUND DATA: Low back pain is a common reason for consulting a health care
      provider, and advice on daily activities constitutes an important part in the
      primary care management of low back pain. METHODS: All randomized studies
      available in systematic searches (electronic databases, contact with authors,
      reference lists) were included. Two reviewers independently selected trials for
      inclusion, assessed the validity of the included trials, and extracted data.
      Investigators were contacted to obtain missing information. RESULTS: Four trials,
      with a total of 491 patients, were included. In all the trials, advice to stay
      active was compared with advice for bed rest. Two trials were assessed as having
      a low risk of bias, and two as having a moderate to high risk of bias. The
      results were heterogeneous. The results from one high-quality trial of patients
      with acute, simple low back pain found small differences in functional status
      (weighted mean difference on a 0 to 100 scale, 6.0; 95% CI, 1.5-10.5) and length
      of sick leave (weighted mean difference, 3.4 days; 95% CI, 1.6-5.2) in favor of
      staying active, as compared with advice to stay in bed 2 days. The other high
      quality trial compared advice to stay active with advice to rest in bed 14 days
      for patients with sciatic syndrome, and found no differences between the groups.
      One of the high-quality trials also compared advice to stay active with advice to
      engage in exercises for patients with acute, simple low back pain, and found
      improvement in functional status and reduced sick leave in favor of advice to
      stay active. CONCLUSION: The best available evidence suggests that advice to stay
      active alone has little beneficial effect for patients with acute, simple low
      back pain, and little or no effect for patients with sciatica. There is no
      evidence that advice to stay active is harmful for either acute low back pain or
      sciatica. Because there is no considerable difference between advice to stay
      active and advice for bed rest, and there are potential harmful effects of
      prolonged bed rest, it is reasonable to advise people with acute low back pain
      and sciatica to stay active. These conclusions are based on single trials.

PMID- 12195065
TI  - Surgical treatment of idiopathic scoliosis in adults: an age-related analysis of
      outcome.
AB  - STUDY DESIGN: A retrospective outcome study was conducted. OBJECTIVE: To analyze
      the clinical and radiographic outcome of surgical treatment for idiopathic
      scoliosis in patients treated at the age of 20 years or older. SUMMARY OF
      BACKGROUND DATA: Idiopathic scoliosis continues to pose problems in many patients
      after adolescence. Surgical treatment of idiopathic scoliosis in adults still is
      a challenging subject, but no outcome analysis in terms of different age groups
      had been performed. METHODS: In this study, 58 adult patients with idiopathic
      scoliosis who underwent surgery using Cotrel-Dubousset instrumentation were
      followed up for 2 to 7 years, and the results were studied clinically and
      radiographically. RESULTS: The prevalence of pain that requires specific
      treatment decreased from 16% to 5%, and the pain improvement was reliably
      obtained in the older patients. Radiographically, the mean rate of Cobb angle
      correction was 53% for both the thoracic and lumbar curves, whereas it decreased
      age dependently, especially in relation to the thoracic curve. The sagittal plane
      correction generally was satisfactory in patients younger than 50 years, but
      appropriate lumbar lordosis was difficult to maintain after the age of 50 years.
      Frontal and sagittal balance often was difficult to achieve in patients older
      than 50 years. CONCLUSIONS: This study clarified specific characteristics and
      problems in the surgical treatment of adult idiopathic scoliosis according to
      different age groups. Although pain was the most important indication for surgery
      in patients older than 40 years, it was improved reliably by surgery in most of
      these patients. On the other hand, the radiographic results tended to be less
      satisfactory in the older patients in an age-dependent manner. These results
      provide useful information concerning the indications and strategies of adult
      scoliosis surgery.

PMID- 12195067
TI  - Point of view.

PMID- 12195066
TI  - Fast MRI used to evaluate the effect of abdominal belts during contraction of
      trunk muscles.
AB  - STUDY DESIGN: This study focused on the effects that abdominal belts have on the
      sagittal section of the abdominal and pelvic cavity during contraction of the
      trunk muscles. Fast magnetic resonance imaging was used during the Valsalva
      maneuver by 11 healthy men. OBJECTIVE: To evaluate the effect of an abdominal
      belt on the geometric changes in the sagittal section during Valsalva maneuvers.
      SUMMARY OF BACKGROUND DATA: Several hypotheses about the effect of an abdominal
      belt have considered intraabdominal pressure, which has a hydraulic effect on the
      diaphragm, providing stability to the spine. However, there is little information
      on changes in the sagittal section of the abdominal and pelvic cavity. METHODS:
      Eleven male volunteers without back problems were studied with fast magnetic
      resonance images. Sagittal section images of the abdominal and pelvic cavity were
      obtained under six conditions: without the belt at rest, at full inhalation, and
      at full inhalation with Valsalva, as well as with the belt at rest, at full
      inhalation, and at full inhalation with Valsalva. RESULTS: When the belt was
      worn, the sagittal section area of the abdominal and pelvic cavity did not
      change, but its shape did. Also, the anteroposterior diameter of the abdominal
      and pelvic cavity increased at its upper part and decreased at its middle part,
      elevating the liver and diaphragm. Additionally, the lever arm length of the
      intraabdominal pressure increased significantly. CONCLUSIONS: Fast magnetic
      resonance imaging quantified the effect of an abdominal belt on the abdominal
      geometric changes during the Valsalva maneuvers with the patient in a supine
      position.

PMID- 12195068
TI  - Spatial and temporal localization of transforming growth factor-beta, fibroblast
      growth factor-2, and osteonectin, and identification of cells expressing alpha
      smooth muscle actin in the injured anulus fibrosus: implications for
      extracellular matrix repair.
AB  - STUDY DESIGN: The spatial and temporal localization of fibroblast growth factor
      2, transforming growth factor-beta, osteonectin, and alpha-smooth muscle cell
      actin in the injured anulus fibrosus was investigated. OBJECTIVE: To assess the
      involvement of fibroblast growth factor-2, transforming growth factor-beta,
      osteonectin, and alpha-smooth muscle cell actin in anulus fibrosus repair.
      SUMMARY OF BACKGROUND DATA: Fibroblast growth factor-2 and transforming growth
      factor-beta have been localized to disc herniation tissue, and alpha-smooth
      muscle cell actin has been identified in a number of mesenchymal cell types, but
      their roles have not been evaluated in repair processes in the experimentally
      injured anulus fibrosus. METHODS: For this study, 32 two adult merinos received a
      4-mm deep standard annular incision in their L1L2 and L3L4 discs (lesion group).
      A similar number of sham-surgery animals served as control subjects. Osteonectin,
      fibroblast growth factor-2, transforming growth factor-beta, and alpha-smooth
      muscle cell actin were immunolocalized in sagittal disc sections 3, 6, 12, and 26
      months after the operation. Selected specimens also were stained with hematoxylin
      and eosin, Masson-trichrome, toluidine blue, and picrosirius red. RESULTS: Early
      focal depletion of proteoglycan was evident in the anulus fibrosus and
      reorganization of outer annular lamellas 3 to 6 months after the operation. Blood
      vessel ingrowth and fibroblast infiltration from the outer anulus fibrosus along
      the plane of the annular defect were maximal 12 months after the operation. Focal
      upregulation in alpha-smooth muscle cell actin expression was evident with
      maximal staining in the 12-month lesion samples near infiltrating blood vessels
      at the lesion site, and also in cells well away from these vessels. Some of the
      anulus fibrosus cells of the sham sections also stained positively for alpha
      smooth muscle cell actin, but this staining was significantly less than in the
      lesion samples. Staining for fibroblast growth factor-2, transforming growth
      factor-beta, and osteonectin was strongly localized to blood vessels and cells in
      the vicinity of the annular lesion. It was maximal 12 months after the operation
      and diminished by 26 months after the operation. Osteonectin expression also was
      significantly elevated in outer anulus fibrosus cells distant from the lesion
      site and its associated blood vessels. In the sham discs, immunoreactivity to
      fibroblast growth factor-2, transforming growth factor-beta, osteonectin, and
      alpha-smooth muscle cell actin was confined to sparsely distributed cells in the
      anulus fibrosus. No matrix staining was observed. CONCLUSIONS: Immunoreactivity
      for the noted agents was strongly associated with regions of the annular lesions
      undergoing matrix reorganization consistent with an active repair response. This
      response extended as far as the middle third of the anulus fibrosus, which also
      demarcated the extent of blood vessel ingrowth and cellular infiltration in this
      model. The alpha-smooth muscle cell actin expression suggested an active
      involvement of myofibroblasts in the anulus fibrosus repair processes.

PMID- 12195069
TI  - Association of bone metabolism regulatory factor gene polymorphisms with
      susceptibility to ossification of the posterior longitudinal ligament of the
      spine and its severity.
AB  - STUDY DESIGN: A case-control association study and a stratified study
      investigating the genetic etiology for ossification of the posterior longitudinal
      ligament of the spine. OBJECTIVE: To determine the association of restriction
      fragment length polymorphisms of estrogen receptor, vitamin D receptor,
      parathyroid hormone, and interleukin-1alpha and -1beta with susceptibility to
      ossification of the posterior longitudinal ligament of the spine and its
      severity. SUMMARY OF BACKGROUND DATA: Contribution of genetic backgrounds to the
      etiology for ossification of the posterior longitudinal ligament of the spine has
      been suggested by epidemiologic studies. METHODS: Genomic deoxyribonucleic acid
      samples obtained from 120 patients (77 men and 43 women) with ossification of the
      posterior longitudinal ligament of the spine and 306 control subjects without the
      disorder (166 men and 140 women) were amplified by polymerase chain reaction, and
      polymorphism genotypes were determined by restriction endonuclease digestion. The
      distribution of genotypes was compared between patients with the disorder and
      control subjects. In addition, the severity of ossification was determined by the
      number of ossified vertebrae in patients with the disorder, and associations of
      the severity with age, gender, and genotypes were examined. RESULTS: Estrogen
      receptor (P = 0.007) and interleukin-1beta (P = 0.001) polymorphisms exhibited
      different distributions between patients with ossification of the posterior
      longitudinal ligament of the spine and control subjects in women, but not in men.
      In patients with the disorder, the severity of ossification was negatively
      correlated with age in women (P = 0.013), but not in men. Estrogen receptor
      polymorphism was associated with the severity only in women (P = 0.001).
      CONCLUSIONS: The contribution of genetic backgrounds is likely to be stronger in
      women than in men with ossification of the posterior longitudinal ligament of the
      spine. Estrogen receptor polymorphism was associated with both initiation and
      promotion of the disorder, but interleukin-1beta polymorphism was associated only
      with its initiation in women.

PMID- 12195070
TI  - Back extension endurance and strength: the effect of variable-angle roman chair
      exercise training.
AB  - STUDY DESIGN: A pre- and postintervention randomized, controlled trial was
      conducted. OBJECTIVE: To evaluate the effect of progressive resistance exercise
      training using a variable-angle Roman chair on the development of lumbar extensor
      endurance and strength. SUMMARY OF BACKGROUND DATA: Progressive resistance
      exercise for the lumbar extensors has been used successfully for low back pain
      rehabilitation, but the limitations of currently available back exercise devices
      have negatively affected its use. METHODS: For this study, 36 healthy volunteers
      were randomized into one of two groups: a variable-angle Roman chair exercise
      group (n = 18) that performed one set of 15 to 25 repetitions of dynamic
      progressive resistance back extension exercise on a variable-angle Roman chair
      three times per week for 8 weeks or a control group (n = 18) that did not perform
      resistance exercise. Before training and after 4 and 8 weeks of training, static
      back extension endurance (seconds) and isometric lumbar extension strength
      (Newton.meters) were recorded. RESULTS: The variable-angle Roman chair exercise
      group displayed a 42% increase in static back extension endurance at the 4-week
      and 8-week tests relative to the pretraining measure (P < 0.05). The control
      group did not increase back endurance time at either the 4-week or 8-week tests
      (P > 0.05). Neither the variable-angle Roman chair exercise group nor the control
      group displayed an increase in lumbar extension strength at the 4-week or 8-week
      tests (P > 0.05). CONCLUSIONS: Dynamic progressive resistance exercise training
      on a variable-angle Roman chair is capable of developing back extension
      endurance. Future research is needed to determine the clinical applicability of
      variable-angle Roman chair exercise training for patients with low back pain
      patients.

PMID- 12195071
TI  - The six-month incidence of clinically significant low back pain in the
      Saskatchewan adult population.
AB  - STUDY DESIGN: A population-based, longitudinal, mailed survey was conducted.
      OBJECTIVE: To investigate the 6-month incidence and determinants of clinically
      significant low back pain in the Saskatchewan adult population. SUMMARY OF
      BACKGROUND DATA: Few studies have investigated the incidence of significant low
      back pain in general populations. When available, such studies often differ in
      the assessment of pain severity. This lack of consensus in measuring pain
      severity results in large differences in incidence rates. METHODS: A
      questionnaire requesting information on low back pain and other health conditions
      was mailed to randomly chosen individuals, ages 20 to 69, residing in the
      province of Saskatchewan, Canada. Of the 1131 (55%) who responded at baseline,
      848 had not experienced clinically significant low back pain during the past 6
      months. Clinically significant low back pain was assessed using the Chronic Pain
      Questionnaire, a 7-item scale that measures the intensity of chronic pain and
      associated disability. Individuals with no clinically significant low back pain
      were followed up at 6 months. RESULTS: At the follow-up assessment, 50
      individuals reported clinically significant low back pain, representing a
      cumulative incidence of 8% (95% confidence interval, 6-10.4). In logistic
      regression models, marital status, rural residency, and history of back and neck
      pain were associated with the onset of clinically significant low back pain.
      CONCLUSIONS: The 6-month incidence of clinically significant low back pain is
      high in Saskatchewan. It is important to prevent this condition because of the
      high economic and social costs associated with it.

PMID- 12195073
TI  - A prospective cohort study of risk factors for disability retirement because of
      back pain in the general working population.
AB  - STUDY DESIGN: A 7-year prospective cohort study of 34,754 employed men and women
      was conducted. OBJECTIVE: To determine the relative contribution of occupational
      risk factors, lifestyle factors, comorbidity, and psychological and social
      factors to the incidence of disability retirement because of back pain in the
      general working population. SUMMARY OF BACKGROUND DATA: Permanent occupational
      disability is a serious consequence of a disabling process. Although this
      condition is a great burden to the individual and extremely costly for society,
      few population-based studies exist on risk factors for obtaining disability
      pension because of back pain. METHODS: Patients granted back pain disability
      pension were ascertained from the national disability register. The exposure
      variables were taken from a health screening of all the inhabitants in one
      county: Norway. The participation rate was 72% to 90%. RESULTS: During the follow
      up period, 715 individuals (2.1%) were granted a back pain disability pension. In
      the final combined multivariate model, the strongest predictors for future back
      pain disability were the occupational risk factor "physically demanding work"
      (odds ratio [OR], 4.1; 95% confidence interval [CI], 2.7-6.4) and the comorbidity
      factor "poor general health" (OR, 3.7; 95% CI, 2.4-5.8). "Feeling of being worn
      out" (OR, 1.7; 95% CI, 1.1-2.4), current smoking (OR, 1.4; 95% CI, 1.2-1.7), and
      body mass index in the upper percentile (OR, 1.6; 95% CI, 1.2-2) also predicted
      back pain disability pension. CONCLUSIONS: In a broad public health perspective
      within a European welfare system, subjects at high risk for future back pain
      disability pension perceived their work as constantly physically demanding, had
      health complaints other than back pain, and mostly felt generally tired and worn
      out. The results indicate that interventions directed toward the painful back
      alone may be unsuccessful in preventing disability pensions.

PMID- 12195072
TI  - Using the dallas pain questionnaire to classify individuals with low back pain in
      a working population.
AB  - STUDY DESIGN: Individuals with low back pain were classified by cluster analysis
      of their responses to the Dallas Pain Questionnaire. These results enabled
      development of an alternative simple classification tool that yielded results
      close to those obtained by the cluster analysis. OBJECTIVES: To use the Dallas
      Pain Questionnaire to classify workers with low back pain, and to develop a
      practical classification tool for physicians. SUMMARY OF BACKGROUND DATA: The
      severity of low back pain is important information for patient management.
      Questionnaires exploring the multidimensional aspect of low back pain have been
      used to classify individuals with low back pain. The Dallas Pain Questionnaire is
      a short self-administered questionnaire that explores the functional and
      emotional aspects of chronic low back pain. It was tested in a population still
      at work using a simplified scoring system. METHODS: The study included 765
      persons with low back pain still at work who completed the self-administered
      questionnaire. Of these patients, 732 could be classified by cluster analysis
      according to their answers to the Dallas Pain Questionnaire. A classification
      tool was developed to categorize them. Using external variables, the groups thus
      formed were compared. RESULTS: Respondents were classified into four classes:
      class 1 (minor disability), class 2 (intermediate disability), class 3
      (disability for some physical activities), and class 4 (physical disability and
      emotional disturbance). External pain-related variables were clearly associated
      with increasing low back pain severity as measured by this classification tool.
      CONCLUSIONS: The Dallas Pain Questionnaire discriminated between different groups
      of persons with low back pain. The proposed classification uses a short, simple
      practical tool to assess different levels of low back pain.

PMID- 12195074
TI  - Computerized questionnaires and the quality of survey data.
AB  - STUDY DESIGN: A retrospective data quality analysis was conducted. OBJECTIVE: To
      compare missing response rates and internal consistency between computerized and
      paper surveys administered to spine patients. SUMMARY OF BACKGROUND DATA:
      Computerized patient surveys have been shown to offer numerous advantages over
      traditional paper surveys. It has been assumed that computerized surveys also
      improve data quality, but quantitative comparisons have not been made. METHODS:
      Between January 1998 and December 2000, approximately 3500 computerized
      questionnaires and 15,000 paper questionnaires containing the MOS 36-Item Short
      Form Health Survey (SF-36) and the Oswestry Low Back Pain Disability
      Questionnaire were administered in the National Spine Network. Missing response
      rates and the Response Consistency Index (RCI) were compared between computerized
      and paper questionnaire data. RESULTS: Computer surveys had approximately half
      the missing response rate of paper surveys. For the SF-36, the computer survey
      had 1.7% missing, as compared with 3.3% missing on paper (P < 0.001). For the
      Oswestry, the computer survey had 2.9% missing, as compared with 6% missing on
      paper (P < 0.001). Whereas 84% of the SF-36 surveys and 85% of the Oswestry
      surveys collected by computer were completely filled out (no missing responses),
      only 68% of the SF-36 surveys (P < 0.001) and 77% of the Oswestry surveys (P <
      0.001) collected on paper were completely filled out. The SF-36 data collected by
      computer had better internal consistency than the paper-form data, with average
      Response Consistency Index scores of 0.12 and 0.16, respectively (P = 0.001).
      CONCLUSIONS: Superior response rates and higher internal consistency suggest that
      computerized survey systems improve data quality, and may enhance instrument
      validity for commonly used measures of spine patient health.

PMID- 12195076
TI  - A kyphectomy technique with reduced perioperative morbidity for myelomeningocele
      kyphosis.
AB  - STUDY DESIGN: The lumbar sacropelvis in 11 patients with myelomeningocele and
      kyphosis was treated with a subtraction kyphectomy technique and posterior
      instrumentation. The results of this procedure in the 11 patients were evaluated
      and compared with previous results. OBJECTIVE: To examine critically their
      experience using the subtraction (decancellation) vertebrectomy technique
      combined with posterior instrumentation for myelomeningocele kyphosis, the
      authors reviewed the charts of 18 myelomeningocele patients who underwent surgery
      for lumbar kyphosis between 1994 and 1998. SUMMARY OF BACKGROUND: The benefits of
      restoring sagittal spinal alignment in myelomeningocele patients with severe
      lumbar kyphosis deformity to achieve postural stability and improved sitting
      balance generally are accepted. The optimal method of deformity correction, the
      extent of instrumentation, and the role of limited arthrodesis remain undefined.
      METHODS: Of the 18 patients considered, 11 met the inclusion criteria of having
      undergone reconstruction using a subtraction (decancellation) vertebrectomy
      technique, preservation of the thecal sac, limited arthrodesis with posterior
      transpedicular lumbosacral instrumentation, and a minimum follow-up evaluation of
      2 years. The study considered the age of the patient, number of levels fused,
      estimated blood loss, preoperative deformity, immediate postoperative correction,
      magnitude of correction, and maintenance of correction at latest follow-up
      assessment. RESULTS: The average age at the time of the index procedure was 6
      years (range, 3-12 years). The average preoperative kyphosis was 88 degrees
      (range, 50-149 degrees ). Immediately after surgery, the average curve
      measurement was 3 degrees lordosis (range, 50 degrees to 50 degrees ). The
      average magnitude of postoperative sagittal plane deformity correction was 91
      degrees (range, 43-126 degrees ). Finally, the magnitude of correction maintained
      at the final follow-up assessment averaged 66 degrees (range, 22-114 degrees ).
      This represented an average loss of correction at 2 years of 24 degrees (range, 0
      84 degrees ). There were no deaths, episodes of acute-onset hydrocephalus,
      vascular complications, or chronic deep wound infections. CONCLUSIONS: The
      subtraction (decancellation) vertebrectomy technique with preservation of the
      dural sac is a safe and efficacious technique for correction and stabilization of
      myelomeningocele kyphosis in young patients. Morbidity is reduced, as compared
      with that of excision techniques. Restoration of sagittal alignment at the time
      of initial correction and stabilization to achieve a balanced spine led to
      acceptable results.

PMID- 12195075
TI  - Surgery for solitary metastases of the spine: rationale and results of treatment.
AB  - STUDY DESIGN: A spine tumor database of patients with solitary sites of spine
      involvement from solid tumors was retrospectively reviewed. OBJECTIVES: To
      analyze the long-term survival, neurologic outcome, and results of surgery in a
      well-defined subset of patients who had spinal metastases with epidural extension
      to define future treatment strategies. SUMMARY OF BACKGROUND DATA: Currently
      accepted indications for surgical treatment of spinal metastases include
      histologic diagnosis, neurologic palliation in those who have failed prior
      irradiation, and spinal stabilization. In all others, external irradiation is
      considered the mainstay of therapy. Several studies have shown that prior
      irradiation increases the frequency of complications from surgery and affects
      functional outcome. METHODS: A retrospective review of 80 consecutive patients
      with solitary sites of spine involvement from solid tumors with varying degrees
      of epidural extension was performed. Complete clinical and radiologic follow-up
      assessment was available for all the patients. Clinical parameters, neurologic
      grade, preoperative pain, radiologic evaluation, and outcome measures were
      analyzed. Survival analysis was performed using the Kaplan-Meier product limit
      method, and differences between subgroups were analyzed using chi2. Prognostic
      factors for long-term survival also were evaluated. RESULTS: The overall median
      survival after surgery was 30 months, with 18% surviving 5 years or more.
      Survival varied by tumor type, with the best prognosis noted in patients with
      breast or kidney cancer. The surgical morbidity was significantly higher in those
      receiving prior irritation (P < 0.03), and the local recurrence rate also
      increased in patients who had received prior irradiation. CONCLUSIONS: Patients
      with solitary sites of spine involvement from solid tumors represent a
      biologically favorable subgroup with potential for long-term survival. In this
      group, complete surgical excision before irradiation should be considered to
      increase the prospects of long-term palliation and possible cure.

PMID- 12195077
TI  - Unknown case: Part II.

PMID- 12195078
TI  - Acute progression of spondylolysis to isthmic spondylolisthesis in an adult.
AB  - STUDY DESIGN: Acute progression of spondylolysis to spondylolisthesis in an adult
      without degenerative disc disease at the slip level is reported. OBJECTIVE: To
      document a case of adult-onset progression of isthmic spondylolisthesis, in which
      the disc space height at the slip level was normal. There were no known risk
      factors for progression, and the olisthesis occurred acutely after minimal
      trauma. SUMMARY OF BACKGROUND DATA: Adult progression of spondylolysis to
      spondylolisthesis is reported infrequently because the highest risk for slip
      progression is before skeletal maturity. Previous reports documenting progressive
      slips in adults have uniformly related the olisthesis to progressive disc
      collapse and subluxation below the pars defect. METHODS: A 39-year-old woman was
      evaluated for a primary complaint of back and bilateral leg pain. Standing
      radiographs of her lumbar spine showed an L4-L5 and L5-S1 spondylolysis without
      spondylolisthesis. She had severe degenerative disc changes at L5-S1. The disc
      space height was normal at L4-L5. Two years later she was essentially immobilized
      by back pain after minimal trauma. Standing radiographs demonstrated a new Grade
      2 L4-L5 isthmic spondylolisthesis. As demonstrated by magnetic resonance imaging,
      spontaneous reduction of the olisthesis has occurred with normal disc space
      height maintained. RESULTS: An L4-S1 anterior lumbar interbody fusion and
      posterior decompression and spinal fusion with instrumentation were performed
      without complication. At this writing, the patient has returned to work and is
      doing well 1 year after surgery. CONCLUSIONS: This case is important because it
      illustrates the potential for acute progression of spondylolisthesis with minimal
      trauma. A patient with known spondylolysis who sustains acute severe exacerbation
      of his or her back pain should have repeat standing radiographs.

PMID- 12195079
TI  - Disc herniation after lumbar fusion.
AB  - STUDY DESIGN: Eight patients with a herniated disc after lumbar spinal fusion are
      reported. Their clinical features, imaging studies, and management are reported.
      OBJECTIVES: To identify the incidence and features of disc herniation above a
      spinal fusion, and to describe their management. SUMMARY OF BACKGROUND DATA: Late
      complications of lumbar spinal fusions have been reported in the literature, but
      disc herniation has not been specifically addressed in detail. The motion segment
      above a spinal fusion undergoes additional stresses, as documented by increased
      pressure and excessive motion, resulting in degenerative changes. These factors
      likely predispose to disc herniation. METHODS: Of 601 consecutive lumbar fusion
      cases over an 8-year period, herniated nucleus pulposus above the fusion was
      diagnosed in 8 patients. The clinical findings and imaging studies were reviewed,
      including a myelogram computed tomography scan, a magnetic resonance image with
      positive documentation of the herniation, or both. The management of these cases
      was reviewed. RESULTS: Eight patients (1.3%) (4 men and 4 women) were identified,
      whose average age was 56.4 years. Nonoperative treatment failed in six patients.
      Two of these patients underwent simple discectomy, and the remaining four
      underwent discectomy and fusion. All four patients went on to fusion. The average
      time from disc herniation onset to fusion was 28.4 months. CONCLUSIONS: Herniated
      disc after lumbar spinal fusion was found in approximately 1.3% of patients.
      Although rare, this entity that should be considered when patients complain of
      recurring back pain after a lumbar spinal fusion.

PMID- 12195080
TI  - A rare case of lumbosacral meningioma: nondural attachment and possible
      enlargement by orally administered sex steroid.
AB  - STUDY DESIGN: A case report is presented. OBJECTIVES: To present a very rare case
      of orally ingested sex hormone pills inducing nondurally attached meningioma in
      the lumbosacral region. SUMMARY OF BACKGROUND DATA: Meningiomas are known to
      enlarge in response to female sex hormones. At this writing, few cases of
      nondurally based intradural meningioma have been reported. Moreover, meningiomas
      in the lumbosacral region are very rare. Spinal meningiomas predominantly arise
      in the fourth to sixth decades of life and are more common in women. METHODS: The
      patient was a 20-year-old woman. She had undergone oral sex steroid therapy for
      long-term oligomenorrhea. The patient complained of intolerable lumbago and
      numbness in her buttocks. Nonopioid analgesics did not relieve her pain, and she
      was unable to walk without the aid of a walker. Radiography disclosed a
      lumbosacral intradural tumor. RESULTS: Complete removal of the tumor was
      performed. The tumor was not adherent to the dura, and its appearance was that of
      a typical neurilemmoma. However, the pathologic diagnosis was meningioma.
      CONCLUSIONS: The tumor in the reported case may have enlarged in response to
      orally ingested sex steroid pills. Nondural attachment intradural meningiomas are
      quite uncommon. The gross appearance of the tumor during surgery was typical of
      neurilemmoma. All the cases reported so far, including the current case, have
      involved tumor located in the lumbosacral region. Care must be taken in the
      management of lumbosacral intradural tumors because tumors resembling
      neurilemmoma may in fact represent meningioma, some subtypes of which possess a
      high rate of recurrence.

PMID- 12195081
TI  - Severe erosion of lumbar vertebral body because of abdominal aortic false
      aneurysm: report of two cases.
AB  - STUDY DESIGN: Two cases of lumbar vertebral erosion resulting from abdominal
      aortic false aneurysm are reported. OBJECTIVE: To present an uncommon
      complication of aortic endoprosthesis causing spinal pathology. SUMMARY OF
      BACKGROUND DATA: Vertebral body pathologies usually are associated with fracture,
      osteoporotic collapse, tumor, spondylitis, or spondylodiscitis. Aortic abdominal
      aneurysm rarely has been reported as causing lytic lesions of the spine. METHODS:
      A retrospective case analysis was performed for two patients with an aorta
      bifurcation prosthesis and lytic lesions of the spine. False aneurysms were
      detected at the proximal junction of the prostheses. A biopsy of the affected
      vertebrae showed no infection or malignancy. Surgery was performed in both cases,
      and the prostheses were successfully revised. In one case, an anteroposterior
      spinal fusion was performed because of severe anterior bone loss. RESULTS: The
      back pain of both patients resolved completely after surgery. In one of the
      patients, an embolectomy in the right leg failed, and a below-the-knee amputation
      had to be performed. CONCLUSIONS: In patients with endovascular prostheses, false
      aneurysm should be considered when lytic lesions of vertebral bodies are
      differentially diagnosed because these patients can present with only spinal
      symptoms.

PMID- 12195082
TI  - The role of nuclear medicine imaging in routine assessment of infectious brain
      pathology.

PMID- 12195083
TI  - Symposium on therapeutic intervention in nuclear medicine--an introduction.

PMID- 12195084
TI  - Radionuclide therapy of inflammatory joint diseases.
AB  - Inflammatory joint diseases as well as arthropathy are common joint diseases.
      Many of them may be treated by synovectomy to stop disease progression and to
      improve joint function. Radiosynoviorthesis as one therapeutic procedure of
      rheumatoid arthritis, other inflammatory joint diseases, persistent synovial
      perfusion, and other joint diseases is widely used in many countries in Europe.
      Using Y-90 for the knee joint, Re-186 for middle sized joints and Er-169 for
      small joints an improvement of symptoms and function may be observed in about 60
      80% of patients.

PMID- 12195085
TI  - A practical guide to targeted therapy for bone pain palliation.
AB  - Targeted radionuclide therapy is an effective and cost efficient treatment for
      multi-site metastatic bone pain. This paper discusses the physical
      characteristics of the licensed radiopharmaceuticals (153)Sm ethylenediamine
      N,N,N',N'-tetrakis(methylene phosphonic acid) ((153)Sm-EDTMP), (186)Re 1,1
      hydroxyethylidenediphosphonate ((186)Re-HEDP) and (89)SrCl(2) and considers the
      factors influencing treatment choice in specific clinical settings. The
      advantages and practical limitations of this approach are discussed, with
      emphasis on defining criteria for patient selection and response monitoring.
      Opportunities for future research and development are outlined.

PMID- 12195086
TI  - Interventional nuclear medicine in hepatocellular carcinoma and other tumours.
AB  - The range of cancers which can be successfully treated by radioisotopes can be
      expanded by the use of combined pharmacological and physical targeting of the
      relevant radioisotope. This has been used extensively in the management of
      hepatocellular cancer (HCC) which has been treated with (131)I iodized poppy seed
      oil (Lipiodol) or (90)Y labelled glass microspheres infused into the liver under
      radiological control via a catheter placed into the right or left hepatic artery.
      In the treatment of extensive disease survival may not be changed but there is an
      improved quality of life after treatment. If given in the adjuvant setting,
      improved survival has been noted. These techniques have now been applied to other
      tracers for example in the use of (131)I-mIBG in treatment of rare tumours where
      concise localization and destruction of tumours in vital structures needs to
      occur without the risk of damage to surrounding tissues.

PMID- 12195087
TI  - Interventional nuclear medicine in the prevention of restenosis following
      angioplasty.
AB  - Restenosis is an unsolved clinical and economic limitation of angioplasty. Local
      irradiation is a new concept to overcome this problem. The magnitude of this
      health problem becomes apparent when one recognizes that 166132 percutaneous
      transluminal coronary angioplasty (PTCA) procedures were performed in Germany in
      1999. Each angioplasty has subsequent costs of 6384 DM, which can be reduced to
      2161 DM by 50% restenosis reduction due to irradiation [1]. The number of
      diagnostic and therapeutic procedures is growing by at least 10% per year.

PMID- 12195088
TI  - Practical aspects of intra-arterial brachytherapy.
AB  - A wealth of experience exists in brachytherapy delivered in a variety of methods.
      Both beta and gamma sources have been used in the form of wires, pellets and
      liquids introduced through specially designed catheters. In addition, stents have
      been used and work with radioactive gases proposed. A significant issue in such
      interventional work is dosimetry. Presently, many methods and systems are still
      under development undergoing clinical trials and refinement. There is
      considerable uncertainty in the determination of appropriate target volumes and
      dose prescriptions. It is not known whether treatment of only the lumen wall is
      sufficient, or whether the media and adventitia must also be irradiated. Clinical
      trials suggest success depends on delivering adequate dose to target tissues (8
      20 Gy) while limiting normal tissue dose to 30-40 Gy. Some trials indicate that a
      mimimal dose of 8-10 Gy has to be given to the whole media and the upper limit is
      determined by the tolerance of the intima (localized doses of approximately 90 Gy
      have been applied without complications). The requirements for the source for
      endovascular brachytherapy and the small lumen diameters involved compound the
      problems of achieving accurate dosimetry. Discussion of the aspects of radiation
      physics and the sources of dosimetric uncertainty together with the methodology
      used to calculate the dose is presented.

PMID- 12195089
TI  - The importance of the location of fluorodeoxyglucose uptake in periprosthetic
      infection in painful hip prostheses.
AB  - Ten per cent of patients with hip replacement will eventually complain of
      significant pain after surgery, often requiring a revision arthroplasty. The
      majority of these patients experience aseptic loosening rather than infection.
      Despite significant advances made in diagnostic imaging, distinguishing infection
      from aseptic loosening remains a significant challenge. Imaging using
      fluorodeoxyglucose (FDG) positron emission tomography (PET) has been reported to
      have excellent sensitivity in detecting infections associated with hip
      prostheses. However, in some studies, a high rate of false positive results has
      been reported, especially when increased tracer uptake adjacent to the prosthesis
      (which is not surrounded by bone) is used as the sole criterion for diagnosing
      infection. The objective of this investigation was to determine the optimal
      criteria for diagnosing periprosthetic infection, thereby avoiding false positive
      results in this setting. A total of 41 total hip arthroplasties from 32 patients
      and for whom complete clinical follow-up was available were included in this
      analysis. The location and intensity of FDG uptake were determined for each scan.
      Final diagnosis was made by microbiology, histopathology, surgical findings and
      clinical follow-up. Patients who did not undergo surgery were followed up to at
      least 9 months. Twelve patients were proven eventually to have periprosthetic
      infection. Images from 11 of these patients displayed increased tracer uptake
      along the interface between bone and prosthesis. The intensity of the increased
      tracer uptake varied from mild to moderate, with standardized uptake values less
      than 2. In contrast, images from uninfected, loose hip prostheses revealed very
      intense uptake around the head or neck of the prosthesis with standardized uptake
      values as high as 7. It is concluded that the intensity of increased FDG uptake
      is less important than the location of increased FDG uptake when FDG PET is used
      to diagnose periprosthetic infection in patients with hip arthroplasty. Using
      increased uptake as the sole criterion for diagnosing infection will result in
      false positive results in this setting.

PMID- 12195090
TI  - Comparison of fluorodeoxyglucose positron emission tomography and "conventional
      diagnostic procedures" for the detection of distant metastases in breast cancer
      patients.
AB  - The presence of distant metastases is the main prognostic factor in patients with
      breast cancer and has a significant influence in the choice of therapy.
      Therefore, chest X-ray, bone scintigraphy and ultrasound of the abdomen are
      performed to detect distant metastases at diagnosis and follow-up.
      Fluorodeoxyglucose positron emission tomography (FDG PET) has been shown to
      provide sensitive detection of primary tumour and metastases for many tumour
      entities, but little information is available about the diagnostic value for
      breast cancer patients. This study retrospectively compared FDG PET for detection
      of metastatic disease with chest X-ray, bone scintigraphy and ultrasound of the
      abdomen, referred to as "conventional diagnostic procedures" (CDPs), in 50 breast
      cancer patients. Imaging procedures were analysed in a blinded fashion with the
      results classified as "no evidence of metastases", "equivocal" and "evidence of
      metastases". Clinical follow-up and the results of other imaging modalities
      including computed tomography and magnetic resonance imaging were used to
      determine if metastases were present. FDG PET identified metastatic disease with
      a sensitivity and specificity of 86% and 90% as compared to 36% and 95% for CDPs,
      respectively. Regarding "equivocal" and "evidence of metastases" as positive, the
      sensitivity of CDPs increased to 57% with a corresponding specificity of 81%,
      whereas sensitivity and specificity of FDG PET remained unchanged. Regarding
      different localities of metastases the sensitivity of FDG PET was superior in the
      detection of pulmonary metastases and especially of lymph node metastases of the
      mediastinum in comparison to chest X-ray, whereas the sensitivity of FDG PET in
      the detection of bone and liver metastases was of the same magnitude as compared
      with bone scintigraphy and ultrasound of the abdomen.

PMID- 12195091
TI  - Determination of the prognostic value of [(18)F]fluorodeoxyglucose uptake by
      using positron emission tomography in patients with non-small cell lung cancer.
AB  - The aim of this study was to determine whether quantitative information obtained
      from [(18)F]fluorodeoxyglucose positron emission tomography ((18)F-FDG PET) has a
      prognostic significance for patients with non-small cell lung cancer (NSCLC). We
      investigated (18)F-FDG PET imaging of 73 patients with NSCLC. The maximum
      standardized uptake value (SUV(max)) was significantly different between the
      histopathological types of tumour (squamous cell carcinoma (n=37, 12.4+/-5.1),
      adenocarcinoma (n=30, 8.2+/-5.8), bronchioloalveolar carcinoma (n=4, 2.6+/-1.7),
      <0.01). In the univariate analysis of all patients, staging (P=0.0001), tumour
      cell type (P=0.013), and a SUV(max) greater than 7 (P=0.0011) was correlated with
      survival. However, a multivariate analysis identified staging and SUV(max)
      greater than 7 were affected survival adversely. The mortality rate of patients
      with group I disease (stage I to stage IIIA) was 5.8 times lower than that of
      patients with group II disease (stage IIIB to stage IV). Patients with a high
      SUV(max) (> or =7) had a 6.3 times higher mortality than those with a low
      SUV(max)(<7). By multivariate analysis of patients with squamous cell carcinoma,
      only grouping affected survival (P=0.008, relative risk=4.3). In the case of
      adenocarcinoma, the SUV(max) (>10) correlated exclusively with poorer survival
      (P=0.031, relative risk=11.152). (18)F-FDG uptake correlated with survival in
      NSCLC. Especially in adenocarcinomas, the SUV(max) was complementary to other
      known prognostic factors.

PMID- 12195092
TI  - High sensitivity of radiolabelled antimyosin scintigraphy in assessing
      anthracycline related early myocyte damage preceding cardiac dysfunction.
AB  - In antimyosin scintigraphy was evaluated at various cumulative anthracycline dose
      levels in order to early identify patients with severe cardiac injury and
      increased long-term risk of cardiac dysfunction. Twenty-four patients receiving
      standard doses of 60-75 mg.m(-2) doxorubicin or 90-112.5 mg.m(-2) epirubicin were
      followed at baseline, low (two cycles), middle (four cycles), and high (six
      cycles) cumulative dose using (111)In antimyosin 48 h heart-to-lung ratio (HLR),
      left ventricle ejection fraction (LVEF) and peak filling rate (PFR). At a low
      cumulative dose only HLR was significantly increased (P=0.0001); at middle dose
      HLR (P<0.0001) and LVEF (P=0.0054), but not PFR, were significantly changed, and
      at high dose HLR (P<0.0001), LVEF (P=0.0001) and PFR (P=0.033) all changed
      significantly. Concerning individual results, HLR became abnormal in 18 patients
      (75%) at low, 22 (92%) at middle, and 24 (100%) at high cumulative dose whereas
      LVEF and PFR remained within normal limits in all patients. It is concluded that
      myocyte damage appears to precede left ventricle systolic and diastolic
      dysfunction in anthracycline treatment. (111)In antimyosin scintigraphy is very
      sensitive in detecting myocardial damage after cumulative dose levels even as low
      as 120-150 mg.m(-2) doxorubicin or 180-225 mg.m(-2) epirubicin.

PMID- 12195093
TI  - Value and limitation of myocardial fluorodeoxyglucose single photon emission
      computed tomography using ultra-high energy collimators for assessing myocardial
      viability.
AB  - Single photon emission computed tomography (SPECT) using ultra-high energy
      collimators permits wide clinical application of (18)F-fluorodeoxyglucose (FDG)
      imaging without the use of expensive positron emission tomography (PET) cameras.
      This study was designed to evaluate the value of FDG SPECT using ultra-high
      energy collimators in assessing myocardial viability compared with FDG PET on a
      regional basis. We prospectively studied 33 patients with ischaemic heart
      disease. The patients were injected with 555 MBq of FDG under a hyperinsulinaemic
      glucose clamp, and FDG PET was performed 40 min later. FDG SPECT using ultra-high
      energy collimators was performed immediately after FDG PET. The images of the
      left ventricular myocardium were divided into nine segments and the regional
      defect score was assessed visually using a four-point scale (0=normal to
      3=defect). Regional FDG uptake (%uptake) was quantitatively analysed using polar
      maps. In 297 segments of all the 33 patients, agreement between the defect scores
      based on FDG SPECT images and those based on FDG PET images was 70%, and
      agreement within one rank was 96% (kappa value=0.52). The %uptake based on FDG
      SPECT images significantly correlated with that based on FDG PET images (r=0.77,
      P<0.01). However, the defect scores in the inferior wall based on FDG SPECT
      images were higher (1.41+/-1.14) than those based on FDG PET images (1.06+/-1.12,
      P<0.01). When the viable region is defined as %uptake > or =50% in FDG PET
      studies, the optimal cut-off level of %uptake based on FDG SPECT images was 60%
      in the anterior wall, apex, septum and lateral wall (accuracies, 97%, 93%, 96%
      and 99%, respectively), and 45% in the inferior wall (accuracy, 99%). It is
      concluded that FDG SPECT using ultra-high energy collimators can be used for the
      assessment of myocardial viability as accurately as FDG PET. However, a slight
      difference was observed in the defect scores mainly due to attenuation in the
      inferior wall. Therefore, a slightly different cut-off level for assessing
      myocardial viability should be applied to the inferior wall when using FDG SPECT.

PMID- 12195094
TI  - Validation of quantitative gated single photon emission computed tomography and
      an automated scoring system for the assessment of regional left ventricular
      systolic function.
AB  - Despite its ability to quantify regional perfusion and function, there is no
      established method for quantification of regional perfusion and function by
      myocardial gated single photon emission computed tomography (SPECT). The aim of
      this study was to establish a quantitative index for regional perfusion and
      systolic function assessment using gated SPECT. Myocardial SPECT was performed at
      rest using (99m)Tc sestamibi with 8-frame gating in 62 consecutive patients. In
      addition to computation of left ventricular ejection fraction (LVEF), a new
      computerized method for quantifying, displaying and automatically grading
      regional data was developed. Regional function was quantified as wall motion,
      regional EF, and imaged based, count based, and normalized per cent wall
      thickenings (%WTs). Regional perfusion was assessed as a relative per cent peak
      count. Data were displayed on a 25-segmented polar map and automatically graded
      with a 5-point scale, and then summed scores were calculated. These quantitative
      parameters were compared to data from radionuclide ventriculography (RNV) and
      contrast left ventriculography. Gated SPECT had high reproducibilities for
      calculating global and regional ejection fractions and %WT indices (r=0.811
      0.984, P<0.0001), but measurement of wall motion was less reproducible (r=0.555,
      SEE=7.9, P<0.011). LVEF estimated by gated SPECT and summed perfusion scores
      correlated closely (P<0.0001) with angiographic LVEF. Among the summed function
      indices that correlated closely with LVEF, normalized %WT had the closest
      correlations with LVEF estimated by RNV (r=0.657, P<0.0001) and by gated SPECT
      (r=0.778, P<0.0001). Assessment by visual reviewing of cine-mode playback or by
      normalized %WT had greater overall sensitivity, specificity, and positive and
      negative predictive values for detecting impaired regional function among the
      functional parameters: 71%, 79%, 63% and 84% for cine format analysis, and 78%,
      73%, 59% and 87% for normalized %WT, respectively. Thus, besides LVEF,
      quantitative gated SPECT can provide reproducible and reliable quantitative data
      on regional perfusion and function. Automated summed scores obtained by gated
      SPECT can reflect integrated abnormalities of regional perfusion and function of
      the left ventricle. Both visual analyses by cine-mode display and a functional
      map of normalized wall thickening have greater diagnostic values for detecting
      regional function deficit related to coronary artery disease.

PMID- 12195095
TI  - Can the estimation of ejection fraction during gated single photon emission
      computed tomography at rest add information to the cardiac perfusion study?
AB  - Left ventricular function is an important prognostic indicator in patients with
      coronary artery disease. The electrocardiogram gated, myocardial, single photon
      emission tomography (SPECT) program is coming into wide use. This program permits
      measurement of end diastolic volume, end systolic volume, and ejection fraction.
      This study was designed to show whether the measurement of ejection fraction by
      using (99c)Tc tetrofosmin gated SPECT at rest could give additional information
      to the interpretation of perfusion. Exercise 99mTc tetrofosmin SPECT and gated
      (99c)Tc tetrofosmin SPECT at rest were performed in 33 patients with or suspected
      of having coronary artery disease. Left ventricular ejection fraction was
      calculated from reconstructed gated SPECT at rest with a software quantitative
      gated SPECT. The results showed a poor correlation between segmental ejection
      fraction and segmental perfusion in stress and rest. There was an increasing
      probability of reversibility as the ejection fraction increased, while there was
      a greater chance of a fixed defect as the ejection fraction decreased. It is
      concluded that gated SPECT using (99c)Tc tetrofosmin provides clinically
      satisfactory functional data that, in combination with the perfusion information,
      will improve diagnostic and prognostic accuracy without an increase in cost or
      radiation dose to patients.

PMID- 12195096
TI  - SPECT neuropsychological activation procedure with the Verbal Fluency Test in
      attempted suicide patients.
AB  - Performance on the Verbal Fluency Test, as a measure of the ability of initiating
      processes, is reduced in depressed suicidal patients. The hampered results in
      this prefrontal executive task parallel the reduction in prefrontal blood
      perfusion and metabolism in depressed subjects. A neuropsychological activation
      study with the verbal fluency paradigm could evaluate a possible blunted increase
      in perfusion in the prefrontal cortex in depressed suicidal patients. Twenty
      clinically depressed patients who had recently attempted suicide and 20 healthy
      volunteers were included in a single photon emission computed tomography (SPECT)
      split-dose activation study following a verbal fluency paradigm. Statistical
      parametric mapping was used to determine voxelwise significant changes.
      Differences in regional cortical activation between the letter fluency and
      category fluency tasks in attempted suicide patients were found. These patients
      showed a blunted increase in perfusion in the prefrontal cortex. Methodological
      restrictions concerning group uniformity, medication bias and subjective effort
      of the participants are discussed. Our findings indicate a blunted increase in
      prefrontal blood perfusion as a possible biological reason for reduced drive and
      loss of initiative in attempted suicide patients.

PMID- 12195098
TI  - Endothelial dysfunction in essential hypertension: clinical implications.

PMID- 12195097
TI  - Patients with ovarian cancer have elevated (51)Cr-EDTA plasma clearance early
      post-operatively.
AB  - Plasma clearance of (51)Cr-EDTA (Clp(EDTA)) is widely used to determine
      glomerular filtration rate prior to carboplatin based chemotherapy. We have
      observed that many patients with ovarian cancer have elevated Clp in the early
      post-operative phase compared to later phases. The purpose of this study was to
      examine whether this observation reflects a systematic difference. We
      retrospectively analysed data from 53 patients who had undergone surgery for
      ovarian cancer. Twenty-six patients had Clp(EDTA) measured early after the
      operation (mean, 8 days (range, 3-16 days)) (early group), and 27 patients had
      Clp(EDTA) measured late post-operatively (mean, 32 days (range, 19-48 days))
      (late group). Clp(EDTA) values was measured before the first, third and fifth
      course of chemotherapy. Additionally, age, height, weight, cancer stage, ascites
      and tumour histology were noted. Mean Clp(EDTA) in the early group was
      significantly higher than in the late group (104+/-4.4 vs 89+/-3.5 ml.min(-1) per
      1.73 m(2); P =0.005). Clp(EDTA) declined significantly in the early group from
      the first measurement after the operation until measurement before the third
      course of chemotherapy but remained constant in the late group. Clp(EDTA) was not
      correlated to ascites, cancer stage or tumour histology. It is concluded that
      patients with ovarian cancer have significantly higher Clp(EDTA) in the early
      post-operative phase than similar patients with Clp(EDTA) measured late post
      operatively.

PMID- 12195099
TI  - Baroreceptor reflex pathways and neurotransmitters: 10 years on.
AB  - The central nervous system plays a critical role in the management of blood flow
      to the tissues and its return to the heart and lungs. This is achieved by a
      complex interplay of neural efferent pathways, humoral mechanisms and afferent
      pathways. In this review, we focus on recent progress (within the past 10 years)
      that has been made in the sympathetic control of arterial blood pressure with a
      special emphasis on the role of baroreceptor mechanisms and central
      neurotransmitters. In particular, we focus on new features since 1991, such as
      neurotransmission in the nucleus tractus solitarius, the role of neurons in the
      most caudal part of the ventrolateral medulla oblongata and the increasing
      understanding of the exquisite control of different sympathetic pathways by
      different neurotransmitter systems.

PMID- 12195100
TI  - Blood pressure measures, relative and absolute risk, and international
      differences.

PMID- 12195101
TI  - Do diabetes and hypertension interact to accelerate vascular ageing?

PMID- 12195102
TI  - Steps ahead in the non-invasive testing of vascular function.

PMID- 12195103
TI  - Smoking, blood pressure and cardiovascular risk.

PMID- 12195104
TI  - The time-honoured Galilean method and genetic association studies: the importance
      of hypothesis-driven selection of intermediate phenotypes in detecting genes
      associated to hypertension.

PMID- 12195105
TI  - Focus on small artery stiffness.

PMID- 12195106
TI  - Endothelin binding and calcium signalling in hypertension.

PMID- 12195108
TI  - Central effects of mineralocorticoids on blood pressure: new answers, new
      questions.

PMID- 12195107
TI  - Turning up the heat: heat shock proteins, hypertension and cardiovascular risk.

PMID- 12195109
TI  - Purinergic receptors and nitric oxide in experimental hypertension: the effects
      of nitric oxide on P2Y receptor resensitization in spontaneously hypertensive rat
      mesangial cells.

PMID- 12195110
TI  - Antihypertensive effect and end-organ protection of flavonoids: some insights,
      more questions.

PMID- 12195111
TI  - Blood pressure variability, target organ damage and cardiovascular events.

PMID- 12195112
TI  - Pharmacotherapy of obesity: lessons from clinical trials in hypertension.

PMID- 12195113
TI  - Relative role of systolic, diastolic and pulse pressure as risk factors for
      cardiovascular events in the Brisighella Heart Study.
AB  - OBJECTIVE: The objective of this study was to determine the contribution of
      elevated blood pressure parameters to the long-term incidence of cardiovascular
      events. DESIGN: A prospective, population-based longitudinal epidemiological
      cohort. SETTINGS: The population of the town of Brisighella. PATIENTS: The
      Brisighella Heart Study involved 2939 randomly selected residents of Brisighella,
      Italy aged 14 to 84 years, free of cardiovascular (CV) disease at enrollment and
      followed since 1972. Subjects were clinically evaluated at baseline and every 4
      years following enrollment when extensive clinical and laboratory data were
      obtained in addition to the assessment of morbidity and mortality. MAIN OUTCOME
      MEASUREMENTS: The Cox regression analysis, adjusted for the main risk factors for
      CV disease was used to determine the independent prognostic significance of
      systolic, (SBP), diastolic (DBP), and pulse pressure (PP). The events of interest
      were coronary heart disease (CHD) and cerebrovascular disease (CVD). RESULTS:
      Adjusted hazard ratios (HRs) for combined CHD + CVD at SBP categories of 120-139,
      140-159, and 159 mmHg were 1.45 [95% confidence interval, (CI), P= 0.035], 1.88
      (95% CI, P= 0.0008), and 2.31 (95% CI, P<0.0001), respectively. For DBP ranges of
      70-79, 80-89, and 89 mmHg, HRs were 0.91 (95% CI, P= 0.677), 1.33 (95% CI, P=
      0.169), and 1.65 (95% CI, P= 0.029), respectively. PP ranges from 54-67 and 67
      mmHg were associated with HRs of 1.23 (95% CI, P= 0.149), and 1.38 (95% CI, P=
      0.030), respectively. Similar results were seen for CVD and CHD as separate
      endpoints. CONCLUSIONS: The present study demonstrates that SBP is a stronger
      predictor of cardiovascular events than DBP in the Brisighella population. The
      added prognostic significance of PP is also demonstrated, particularly if PP
      exceeds 67 mmHg.

PMID- 12195114
TI  - Diabetes, pulse pressure and cardiovascular mortality: the Hoorn Study.
AB  - OBJECTIVE: Type 2 diabetic patients have an increased arterial stiffness and a
      very high risk of cardiovascular death. The present study investigated the
      relationship between pulse pressure, an indicator of vascular stiffness, and risk
      of cardiovascular mortality among type 2 diabetic and non-diabetic individuals.
      Second, we determined the relationship between pulse pressure and its main
      determinant (i.e. age), and the influence of diabetes and mean arterial pressure
      on this relationship. DESIGN AND METHODS: We studied a cohort of 2484 individuals
      including 208 type 2 diabetic patients. Mean age and median follow-up for non
      diabetic and diabetic individuals, respectively, were 61 and 66 years, and 8.8
      and 8.6 years. One-hundred and sixteen non-diabetic and 34 diabetic individuals
      died of cardiovascular causes. Relative risks of cardiovascular mortality were
      estimated by Cox proportional hazards regression adjusted for age, gender and
      mean arterial pressure. RESULTS: Pulse pressure was associated with
      cardiovascular mortality among the diabetic, but not among the non-diabetic
      individuals [adjusted relative risk (95% confidence interval) per 10 mmHg
      increase, 1.27 (1.00-1.61) and 0.98 (0.85-1.13), P interaction = 0.07]. Further
      adjustment for other risk factors gave similar results. The association, at
      baseline, between age and pulse pressure was dependent on the presence of
      diabetes (P interaction = 0.03) and on the mean arterial pressure (P interaction<
      0.001) (i.e. there was a stronger association when diabetes was present and when
      mean arterial pressure was higher). CONCLUSIONS: We conclude that, in type 2
      diabetes, pulse pressure is positively associated with cardiovascular mortality.
      The association between age and pulse pressure is influenced by the presence of
      type 2 diabetes and by the height of the mean arterial pressure. These findings
      support the concept of accelerated vascular aging in type 2 diabetes.

PMID- 12195115
TI  - Postischemic forearm skin reactive hyperemia is related to cardovascular risk
      factors in a healthy female population.
AB  - OBJECTIVE: To examine whether forearm postischemic skin reactive hyperemia (SRH)
      measured by laser Doppler flowmetry (LDF) can be used to explore microvascular
      function and whether LDF response is related to cardiovascular (CV) risk in a
      population study. METHODS: SRH of the forearm defined as the percentage increase
      in cutaneous blood flow from resting conditions to peak dilation following a 2
      min upper arm occlusion and CV risk factors were measured prospectively in 862
      healthy females screened for cardiovascular risk factors in the context of a
      campaign designed to promote the 'control' of CV risk factors in women. RESULTS:
      The Framingham risk score was constructed from age, sex, systolic and diastolic
      blood pressure, diabetes, total and high-density lipoprotein-cholesterol and left
      ventricular hypertrophy (Cornell product. The Cornell product for women was
      calculated as the QRS duration (ms) (R aVL + S V3 + 6 mV)). Although the score
      was low in this female population (CV event risk at 10 years 7.89) (95%
      confidence interval, 7.49-8.30) aged 40 to 75 years, we observed an inverse
      correlation between SRH of the forearm and the CV risk score ( P<0.001). Hormonal
      replacement therapy (39.4% of the study population was on hormone replacement
      therapy) had no significant influence on forearm postischemic SRH in this
      particular population. CONCLUSIONS: This study shows that in a very low CV risk
      female population, a significant correlation can be observed between the weight
      of CV risks and the impairment of postischemic forearm SRH. Thus, skin laser
      Doppler flowmetry may represent a valuable, simple and non-invasive tool to
      assess and monitor microvascular function in future prospective observational and
      interventional studies.

PMID- 12195116
TI  - Smoking as a modifier of the systolic blood pressure-induced risk of
      cardiovascular events and mortality: a population-based prospective study of
      middle-aged men.
AB  - OBJECTIVE: To examine to what degree smoking habits modulate the relationship
      between systolic blood pressure (SBP) and risk for cardiovascular morbidity
      (first event) and mortality in middle-aged men. DESIGN AND METHODS: In all, 22
      444 middle-aged men were recruited from a population-based screening study (mean
      attendance rate 71%). Risk factor intervention was offered to about 20% of
      participants. Subjects were followed in local and national registers for
      cardiovascular morbidity and mortality during more than 17 years of follow-up.
      Life-style variables were investigated at baseline, including smoking habits.
      Event rates were calculated in relation to quintiles (Q1-Q5) of baseline SBP in
      untreated subjects, subdivided into categories of smoking habits, but also for
      915 previously known, treated hypertensive (tHT) patients at baseline. RESULTS:
      We found an increasing incidence of first cardiovascular event (CE) with
      increasing SBP levels, ranging from 63.5 CE/10 000 person-years (Q1) to 62.3,
      70.5, 82.3 and 115.1 CE/10 000 person-years (Q2-Q5). The corresponding figure in
      tHTs was 153 CE/10 000 person-years. If further subdivided into smokers/ex
      smokers/non-smokers, the relative risks (RR) of smokers were 1.9 [95% confidence
      interval (CI): 1.5-2.4], 2.1 (1.8-2.5), 2.3 (1.8-2.9), 1.8 (1.5-2.1), and 1.7
      (1.5-2.0) compared to present non-smokers, in relation to SBP (Q1-Q5). In tHTs
      the RR was 1.4 (1.1-1.8). Cardiovascular mortality rates differed in relation to
      SBP and smoking habits, from 40.3 (present non-smokers) and 70.7 (smokers)
      deaths/10 000 person-years in Q1, to 54.2 and 134.0 deaths/10 000 person-years in
      Q5. In tHTs the corresponding figures were 81.6 and 149.4 deaths/10 000 person
      years, respectively. No difference in risk was found for never-smokers compared
      to ex-smokers in relation to SBP. The risk in moderate/heavy smokers ( 10
      cigarettes/day) compared to other smokers (<or= 10 cigarettes/day) was
      significantly ( 0.005) increased only in Q5. CONCLUSION: Increasing systolic
      blood pressure levels in middle-aged men is associated with an increasing risk of
      future cardiovascular events and mortality, an association modified by smoking
      habits. Patients with treated hypertension in the 1970-1980s were also at an
      increased risk in spite of healthcare efforts. This calls for a more
      comprehensive multiple risk factor approach for the management and reduction of
      cardiovascular risk in these patients.

PMID- 12195117
TI  - 24-hour blood pressure profile in centenarians.
AB  - OBJECTIVE: Ambulatory blood pressure in the elderly has been studied in the past,
      the age range most frequently examined being 65 to 80 years. The present study
      was aimed at determining 24-h blood pressure means and profile in centennial
      human beings. PATIENTS AND METHODS: Sphygmomanometric blood pressure (average of
      three values) and 24-h ambulatory blood pressure measurements were performed in
      16 centennial subjects (age 101.7 0.4 years, mean SEM) and in 20 healthy
      normotensives aged 80.7 1.1 years. All subjects were in good clinical and mental
      conditions for their age. They had no history, signs or symptoms of
      cardiovascular or non-cardiovascular diseases and were under no drug treatment.
      RESULTS: In the centennial group sphygmomanometric blood pressure amounted to
      131.2 3.0/70.7 2.2 mmHg (systolic/diastolic) and 24-h blood pressure and heart
      rate average values to 125.6 +/- 3.4/64.8 2.0 mmHg and 77.5 4.3 bpm,
      respectively. Blood pressure and heart rate showed no difference between daytime
      and night-time values, i.e. night-time was accompanied by no blood pressure and
      heart rate fall. In contrast, in all subjects, a significant reduction in blood
      pressure was observed during the post-prandial period, with no significant heart
      rate changes. In the octogenarian group, sphygmomanometric and 24-h blood
      pressure averages were 146.6 4.4/82.8 2.2 and 131.8 2.5/75.3 1.6 mmHg,
      respectively, with a clearcut reduction in night-time as well as in post-prandial
      values. CONCLUSIONS: In centenarians 24-h blood pressure values are: (1) lower
      than sphygmomanometric blood pressures and (2) slightly less than in subjects
      aged 80 years. At variance with these subjects, however, in centenarians
      nocturnal hypotension and bradycardia are abolished, presumably because of a
      derangement in the central sleep influences on the cardiovascular system.

PMID- 12195118
TI  - alpha-Adducin Gly460Trp polymorphism, left ventricular mass and plasma renin
      activity.
AB  - OBJECTIVE: Left ventricular hypertrophy (LVH) is associated with an increased
      risk for cardiovascular morbidity and mortality. Epidemiological studies suggest
      that LVH may be influenced by genetic factors. However, the evidence associating
      individual genes with left ventricular (LV) mass is inconsistent and
      contradictory. METHODS: We investigated the association between angiotensin
      converting enzyme insertion/deletion, angiotensinogen and alpha-adducin
      polymorphisms with LV mass and plasma renin activity (PRA) in 162 men with mild,
      never-treated hypertension who were recruited for the Hypertension and Ambulatory
      Recording Venetia Study. The effect of each polymorphism on LV mass and PRA was
      tested in one-way analysis of covariance using LV mass index or PRA as the
      dependent variable after adjusting for covariates. RESULTS: The alpha-adducin
      polymorphism was the only individual polymorphism independently associated with
      LV mass index (F = 7.78, P= 0.006). Patients homozygous for the allele of that
      polymorphism had a LV mass index (123.4 +/- 10.5 g/m(2) ) significantly higher
      compared with heterozygotes (90.8 +/- 2.5 g/m(2) , P<0.01) or homozygotes (94.7
      +/- 1.7 g/m(2) , P<0.05). These subjects also have significantly lower PRA (F =
      4.2, P= 0.017). Albeit uncommon, 40% of homozygotes of the alpha-adducin
      polymorphism had LVH (odds ratio, 15.1; 95% confidence interval, 3.0-82.1).
      CONCLUSIONS: The homozygotic state of the allele of alpha-adducin polymorphism is
      independently associated with increased LV mass and low PRA. These data suggest
      that genetic considerations may contribute importantly to risk stratification,
      and perhaps therapeutic interventions targeted at LVH and the renin-angiotensin
      system in hypertensive patients.

PMID- 12195120
TI  - Interaction between the C(-344)T polymorphism of CYP11B2 and age in the
      regulation of blood pressure and plasma aldosterone levels: cross-sectional and
      longitudinal findings of the Olivetti Prospective Heart Study.
AB  - OBJECTIVE: To study the interaction between the C(-344)T polymorphism and known
      determinants (age, body mass and dietary sodium) of blood pressure and plasma
      aldosterone. DESIGN: Cross-sectional and longitudinal (1980-1995) survey of male
      workers in southern Italy. SETTING: Medical centre of the Olivetti factories.
      PARTICIPANTS: In 1995, the C(-344)T polymorphism was characterized in 811
      untreated men. A subgroup of 280 participants already seen in 1980 was the object
      of longitudinal analysis. MAIN OUTCOME MEASURES: Blood pressure, demographic,
      anthropometric and biochemical variables (serum and urinary electrolytes and
      plasma aldosterone) and frequency of the C(-344)T polymorphism. RESULTS: In the
      whole population, there was no difference among genotypes for any of the
      variables examined. However, multiple regression showed a significant interaction
      between age (but not body mass or sodium intake) and genotype with regard to
      systolic (P = 0.03) and diastolic ( P= 0.02) pressure variability independently
      of covariates. Diastolic pressure increased linearly with age in carriers of the
      T allele (TT, P<0.001 and TC, P= 0.005), but not in CC homozygotes ( P= 0.848).
      In T carriers - but not in CC homozygotes - blood pressure and serum potassium
      increased and plasma aldosterone and serum sodium decreased across quintiles of
      age (P< 0.001 for all trends). In the longitudinal study, diastolic pressure
      increased significantly over time only in T carriers (TC+TT: +2.6 +/- 0.6, versus
      CC: -0.4 +/- 1.5 mmHg, P= 0.04). CONCLUSION: Inter-individual variation of blood
      pressure and plasma aldosterone is affected by the interaction of C(-344)T
      polymorphism and ageing, thus supporting a role for this variant in mechanisms
      affecting blood pressure regulation.

PMID- 12195119
TI  - alpha-Adducin Gly460Trp polymorphism is associated with low renin hypertension in
      younger subjects in the Ohasama study.
AB  - BACKGROUND: The Gly460Trp polymorphism of the alpha-adducin gene (ADD-1 ) has
      been examined as a candidate gene for essential hypertension with salt
      sensitivity in the Caucasian population. However, we failed to detect a positive
      association between the Gly460Trp polymorphism of ADD-1 and hypertension in a
      small series of Japanese subjects. OBJECTIVE: To examine the precise association
      between the Gly460Trp polymorphism of ADD-1 and blood pressure (BP), we carried
      out an association study using a Japanese population: the Ohasama Study. DESIGN:
      Subjects (n = 1490) were recruited from participants in the Ohasama Study, which
      is a cohort in a rural community of northern Japan. METHODS: DNA was extracted
      from the buffy coat of the participants who gave informed consent for genetic
      analysis, and the Gly460Trp polymorphism of ADD-1 was determined by the TaqMan
      polymerase chain reaction method. Various BP values (casual BP, ambulatory BP and
      home BP) were measured in the Ohasama study. We used the mean values of these BP
      measurements for analysis. RESULTS: The frequencies of genotypes in the Ohasama
      population were 23% Gly/Gly, 49% Gly/Trp, and 28% Trp/Trp. In the baseline
      characteristics, age, sex, body mass index, frequency of diabetes and
      hyperlipidemia were significantly different between hypertensive or normotensive
      subjects. In total subjects, all BP values were not different among genotypes. In
      the younger subjects ( 60 years old) with low plasma renin activity (< 1.0 ng/ml
      per h), however, ambulatory BP and home BP were significantly higher in the
      subjects with the Gly/Trp or Trp/Trp genotypes of ADD-1 polymorphism than in
      those with the Gly/Gly genotype. In the same population, the frequency of the
      Gly/Trp or Trp/Trp genotypes of was significantly higher in hypertensives than in
      normotensives (83 versus 72%, chi1(2) = 4.04, P<0.05; odds ratio, 2.12; 95%
      confidence interval, 1.02-4.68). CONCLUSIONS: These findings suggest the
      possibility that the Gly460Trp polymorphism of ADD-1 is associated with low renin
      hypertension.

PMID- 12195121
TI  - Effects of nebivolol and atenolol on small arteries and microcirculatory
      endothelium-dependent dilation in hypertensive patients undergoing isometric
      stress.
AB  - OBJECTIVE: To examine the effects on small arteries and on the cutaneous
      microcirculatory system of nebivolol and atenolol in hypertensive patients.
      DESIGN: Twenty hypertensive patients were randomly assigned to receive nebivolol
      or atenolol in a single-blind, placebo-controlled cross-over study. Piezoelectric
      plethysmography on the third finger, laser Doppler on the third finger at rest
      and after iontophoretic administration of acetylcholine, and pressure-heart rate
      monitoring, were carried out both at rest and during handgrip. The tests were
      performed 45 min after 5 mg nebivolol or 100 mg atenolol administration, then
      repeated 2 days later with a placebo and, after a further 2 days, with atenolol
      or nebivolol again. RESULTS: Both atenolol and nebivolol reduced diastolic blood
      pressure values and heart rate, as well the increase of blood pressure and heart
      rate during handgrip. No change was recorded after placebo. Piezoelectric
      plethysmography showed a significant increase in the ratio between time to peak
      and total time (PT/TT), calculated on the sphygmic wave, during handgrip (0.295
      0.005 versus 0.231 0.015, P<0.005). After nebivolol, a decrease was recorded in
      rest conditions (0.185 0.008 versus 0.231 0.015, P<0.005) with no statistically
      significant increase during handgrip, whereas atenolol showed an increase in the
      PT/TT ratio at rest, with a sustained response during handgrip. Laser Doppler
      showed an increased response to acetylcholine only after nebivolol. CONCLUSIONS:
      Nebivolol and atenolol significantly reduced diastolic blood pressure and heart
      rate, favourably modulating response to handgrip. Nebivolol improved small artery
      distensibility index. Endothelium-dependent cutaneous vasodilation after
      acetylcholine demonstrated a lack of response with atenolol whereas nebivolol
      favourably acts on endothelial function.

PMID- 12195122
TI  - Decreased endothelin binding and [Ca2+]i signaling in microvessels of DOCA-salt
      hypertensive rats.
AB  - OBJECTIVES AND DESIGN: The deoxycorticosterone acetate (DOCA)-salt model of
      hypertension is characterized by elevated vascular endothelin-1 (ET-1) and by
      reduced contraction to ET-1 in isolated mesenteric small arteries. The decreased
      contraction to ET-1 may be a compensatory mechanism caused by elevations in ET-1
      and arterial pressure. The present study was designed to determine whether down
      regulation of endothelin receptors or altered Ca2+ signaling contribute to the
      decreased contraction to ET-1. METHODS AND RESULTS: Contraction to ET-1 (10 to 10
      mol/l) was significantly reduced in isolated mesenteric small arteries (87-286
      microm intraluminal diameter) from DOCA-salt rats compared with placebo rats.
      Membrane protein was obtained for measurement of [125I]ET-1 receptor binding and
      ET receptor expression. Maximum binding was significantly reduced in vascular
      membranes from DOCA-salt rats (670 +/- 71 fmol/mg protein) compared with placebo
      rats (1165 +/- 75 fmol/mg protein), but binding affinity was unchanged.
      Conversely, ETA receptor protein was increased in DOCA-salt rat vessels. To
      assess Ca2+ signaling, freshly dissociated mesenteric small artery smooth muscle
      cells were loaded with fura-2 for measurement of the average myoplasmic free Ca2+
      concentration ([Ca2+ ] ). The ET-1 (10 mol/l) induced increase in [Ca2+ ] was
      significantly less in cells from DOCA-salt rats compared with from placebo rats.
      This effect was not due to a loss of L-type Ca2+ channels since expression was
      increased in membrane protein from DOCA-salt rats compared with placebo rats, as
      measured by Western blot analysis. CONCLUSIONS: These findings indicate that
      decreases in receptor binding and Ca2+ signaling contribute to the impaired
      contraction to ET-1 in DOCA-salt hypertensive rats. However, these changes are
      not due to reduced expression of ETA receptors or L-type Ca2+ channels.

PMID- 12195123
TI  - Effect of YM471, an orally active non-peptide arginine vasopressin receptor
      antagonist, on human vascular smooth muscle cells.
AB  - OBJECTIVE: To investigate the effects of YM471, a non-peptide arginine
      vasopressin (AVP) V1A and V2 receptor antagonist, on the AVP-induced growth
      responses in human vascular smooth muscle cells (VSMCs). METHODS: Binding of
      YM471 to V1A receptors on VSMCs was measured using [3H]AVP. Intracellular free
      Ca2+ concentration was measured by fura 2 fluorescence. Mitogen-activated protein
      (MAP) kinase activity was determined using the p42/p44 MAP kinase specific
      peptide and [gamma- 32P]ATP as substrates. The effect of AVP on hyperplasia and
      hypertrophy of VSMCs was determined by cell number and protein content
      measurements. RESULTS: YM471 potently and concentration-dependently inhibited the
      specific binding of [ 3H]AVP to V1A receptors on VSMCs, exhibiting an inhibition
      constant (Ki ) of 0.35 nmol/l. YM471 inhibited the AVP-induced increase in
      intracellular free Ca concentration with an 50% inhibition concentration (IC50 )
      of 2.01 nmol/l and inhibited the activation of MAP kinase with an IC50 of 6.11
      nmol/l. In addition, AVP concentration-dependently induced hyperplasia and
      hypertrophy in VSMCs, but YM471 prevented these AVP-induced growth effects,
      exhibiting IC50 values of 2.31 and 0.23 nmol/l, respectively. CONCLUSIONS: These
      results indicate that YM471 has high affinity for V receptors on, and potently
      inhibits AVP-induced physiologic responses of, human VSMCs.

PMID- 12195124
TI  - Circulating heat shock protein and heat shock protein antibody levels in
      established hypertension.
AB  - OBJECTIVE: Serum Hsp60 and anti-Hsp65 antibody levels are raised in subjects with
      borderline hypertension, and there is an association between circulating Hsp60
      levels and early atherosclerosis. Given the recognized relationship between
      hypertension and atherosclerosis, this study determined heat shock protein and
      heat shock protein antibody levels in subjects with established hypertension.
      METHODS: Samples from 111 men with hypertension were obtained from the European
      Lacidipine study on Atherosclerosis and samples from 75 normotensive controls
      were taken from a population-screening programme (diastolic pressure, 95 and 80
      mmHg, respectively). Hsp60, Hsp70 and anti-human Hsp60, anti-human Hsp70 and anti
      mycobacterial Hsp65 antibody levels were measured by enzyme immunoassay. Intima
      media thickness (I-M) and the presence of carotid atherosclerosis were determined
      by ultrasonography. RESULTS: Hsp60, Hsp70 and anti-Hsp60 antibody levels in
      hypertension were similar to those in normotensive controls, whereas anti-Hsp70
      and anti-Hsp65 antibody levels were elevated ( 0.001). Hsp60 levels and
      atherosclerosis were not associated. Anti-Hsp70 and anti-Hsp65 antibody levels
      were both associated with hypertension, independently of age, smoking habits and
      blood lipids. CONCLUSIONS: This study demonstrates elevated levels of selected
      heat shock protein antibodies in subjects with hypertension. Although the
      association between heat shock protein antibody levels and human cardiovascular
      stress/disease appears to be robust, the relationship of the latter with heat
      shock protein levels is more complex. Further studies are required before the
      factors inducing, and the clinical significance of, circulating heat shock
      proteins can be evaluated.

PMID- 12195125
TI  - Sympatholytic properties of several AT1-receptor antagonists in the isolated
      rabbit thoracic aorta.
AB  - OBJECTIVE: To evaluate the facilitating effect of angiotensin II on sympathetic
      neurotransmission to quantitatively compare the sympatho-inhibitory potencies of
      the selective AT1 -receptor antagonists losartan, irbesartan and telmisartan in
      the isolated rabbit thoracic aorta. DESIGN: To investigate the influence of
      pharmacological compounds on pre-junctional sympathetic transmission, the
      quantification of sympathetic transmitter release is the most straightforward
      approach. METHODS: To investigate the sympatholytic properties of AT1 -blockers,
      we studied their effects on the enhancement by angiotensin II of electrical field
      stimulation (EFS)-evoked (2 Hz) sympathetic transmission in a modified spillover
      model. RESULTS: Angiotensin II (0.01 nmol/l-0.1 micromol/l) caused a
      concentration-dependent enhancement of EFS-evoked noradrenaline release (control
      versus concentrations 0.1 nmol/l-0.1 micromol/l, P<0.05). The maximal
      augmentation, by almost 100%, was observed at a concentration of 1 nmol/l
      (FR2/FR1, 2.03 +/- 0.11 versus control, 0.99 +/- 0.03). Higher concentrations (up
      to 0.1 micromol/l) produced less than maximal facilitation. The AT1 -receptor
      antagonists losartan (0.1 nmol/l-0.1 micromol/l), telmisartan (0.01-10 nmol/l)
      and irbesartan (0.1 nmol/l-0.1 micromol/l) concentration dependently attenuated
      the angiotensin II-mediated (1 nmol/l) enhancement of EFS-evoked sympathetic
      outflow. The concentrations that reduced the enhancement by 50% (IC50 values,
      expressed as -log mol/l +/- SEM) were 9.05 +/- 0.16 losartan, 10.28 +/- 0.20
      telmisartan and 9.20 +/- 0.23 irbesartan. Accordingly, the order of potency with
      respect to sympatho-inhibition proved telmisartan> irbesartan = losartan (where >
      signifies P<0.05). CONCLUSIONS: The facilitating effect of angiotensin II on the
      sequelae of neuronal stimulation appears to be mediated by pre-synaptically
      located AT1 -receptors. Facilitation can be concentration dependently attenuated
      by AT1 -blockade. The order of potency with respect to sympatho-inhibition is
      telmisartan irbesartan = losartan. These differences may be explained by
      differences in affinity for the pre-synaptic AT1 -receptor.

PMID- 12195126
TI  - Influence of sodium intake on the cardiovascular and renal effects of brain
      mineralocorticoid receptor blockade in normotensive rats.
AB  - OBJECTIVE: We have previously shown that brain mineralocorticoid receptors (MR)
      participate in the control of arterial pressure and renal excretory function in
      normotensive rats. In the present study, we evaluate the influence of sodium
      intake on the control of cardiovascular and renal function by brain MR in
      normotensive conscious rats. We hypothesize that modulation of sodium intake
      affects the cardiovascular and renal effects of brain MR blockade. DESIGN AND
      METHODS: We examined the effect of intracerebroventricular (ICV) administration
      of MR antagonist (RU28318) on systolic blood pressure (SBP), heart rate, and
      urinary excretion of water and electrolytes in normotensive Wistar rats subjected
      to different dietary sodium content. Rats were fed high (8%), normal (0.4%), or
      depleted (0%) sodium for 3 weeks. SBP and heart rate measurements were performed
      using an indirect tail cuff method. Metabolic cages were used to assess renal
      function. RESULTS: ICV injection of 100 ng RU28318 induced a long-lasting
      decrease ( 0.01) in SBP in rats submitted to different sodium intake. At 8 h, the
      decrease in SBP did not differ between rats on high (30 +/- 5 mmHg), normal (28
      +/- 6 mmHg), and low (21 +/- 3 mmHg) sodium diets. At 24 h, the decrease in SBP
      was also comparable between rats on different sodium diets. Increased diuresis
      was observed during the period 0-8 h after ICV injection of RU28318; this was
      less pronounced in rats on the low sodium diet. Urinary excretions of potassium
      and chloride were also increased during this period, particularly in rats on the
      high and normal sodium diets compared with rats with low sodium intake. Urinary
      excretion of sodium was increased only in the rats fed high and normal sodium
      diets. Measurement of plasma renin activity, which was suppressed and stimulated,
      respectively, by high and low sodium intake, indicated that the effects on SBP
      and renal function induced by ICV RU28318 were independent from the level of
      activation of the renin-angiotensin system. CONCLUSION: In contrast to our
      hypothesis, in normotensive Wistar rats, sodium intake does not affect the
      hypotension induced by brain MR blockade. However, sodium depletion attenuated
      the renal effects of brain MR blockade.

PMID- 12195127
TI  - Effects of nitric oxide on P2Y receptor resensitization in spontaneously
      hypertensive rat mesangial cells.
AB  - BACKGROUND: Cellular responses to agonists of G protein-coupled receptors are
      usually rapidly attenuated - a process known as 'receptor desensitization'. The
      mechanisms that attenuate signalling are important both physiologically and
      therapeutically. OBJECTIVE: To evaluate the effects of nitric oxide on the P2Y
      receptor resensitization in cultured glomerular mesangial cells in spontaneously
      hypertensive rats (SHRs) and Wistar-Kyoto (WKY) rats. METHODS: The cytosolic
      calcium concentration ([Ca2+]i ) in cultured mesangial cells was determined with
      a fluorescence digital imaging system, using the intracellular fluorescent
      indicator, Fura 2-AM. RESULTS: The first ATP-stimulated [Ca2+]i measured was
      significantly greater in SHRs (1330.25 +/- 360.31 nmol/l) than in WKY rats
      (974.28 +/- 397.72 nmol/l; 0.05). Spermine- -[4-[1-(3-aminopropyl)-2-hydroxy-2
      nitrosohydrazino]-butyl-1,3-propanediamine (spermine NONOate) and L-arginine
      significantly increased the fourth ATP-stimulated [Ca2+]i in WKY rats ( P<0.01,
      0.05, respectively). In SHRs, only spermine-NONOate was able to restore the
      fourth ATP-challenged [Ca2+]i value significantly. Nomega-nitro-L-arginine methyl
      ester (L-NAME) greatly reduced the second, third and fourth ATP-stimulated
      [Ca2+]i in WKY rats (P< 0.01), but not in SHRs. When the cells from WKY rats were
      superfused with L-NAME, L-arginine or spermine-NONOate for a period of 5 min
      before and during one single ATP challenge, the responses observed were not
      significantly different from those in controls. CONCLUSIONS: L-Arginine and
      spermine-NONOate are able to increase P2Y receptor resensitization in rat
      mesangial cells, an effect that is less potent in SHRs than in WKY rats. The
      presence of >l-NAME enhanced receptor desensitization in WKY rats, but not in
      SHRs.

PMID- 12195128
TI  - Protective effects of the flavonoid quercetin in chronic nitric oxide deficient
      rats.
AB  - OBJECTIVES: The present study analysed, for the first time, the effects of the
      flavonoid quercetin in rats after chronic inhibition of nitric oxide (NO)
      synthesis with Nomega-nitro-L-arginine methyl ester (L-NAME). DESIGN: Rats were
      divided randomly into five different treatment groups for 6 weeks: (1) vehicle
      (control, 1 ml of 1% methylcellulose once daily); (2) vehicle plus L-NAME (75
      mg/100 ml in drinking water); (3) quercetin (10 mg/kg p.o. once daily); (4)
      quercetin (5 mg/kg p.o.) plus L-NAME; and (5) quercetin (10 mg/kg p.o.) plus L
      NAME. METHODS: The evolution of systolic blood pressure, morphological variables,
      proteinuria, plasma malondialdehyde and nitrite and nitrate concentrations,
      hepatic glutathione and malondialdehyde content, glutathione enzymes activity and
      vascular reactivity at the end of the experiment were analysed. RESULTS:
      Quercetin markedly inhibited the development of L-NAME-induced hypertension. This
      effect was accompanied by a partial or full prevention of most of the effects
      induced by L-NAME, such as: (1) increases in the left ventricular and kidney
      weight indices; (2) proteinuria; (3) renal histological lesions, including
      hyaline arteriopathy and thickening of the vascular wall with moderate decrease
      of the lumen; (4) increased endothelium-dependent contraction; (5) increased
      vascular thromboxane B2 (TXB2) synthesis; (6) reduced plasma concentrations of
      nitrites plus nitrates (NOx); (7) increased plasma and hepatic malondialdehyde
      (MDA) concentrations; and (8) reduced glutathione peroxidase activity. In most
      cases these effects were dose dependent, but none of them were observed in
      normotensive animals. CONCLUSIONS: This study confirms and extends the previous
      evidence about the antihypertensive effects and end-organ protection of the
      flavonoid quercetin in animal models of hypertension.

PMID- 12195130
TI  - The importance of blood pressure variability in rat aortic and left ventricular
      hypertrophy produced by sinoaortic denervation.
AB  - OBJECTIVE: The main objective was to examine the role of hemodynamics in rat
      aortic and left ventricular hypertrophy produced by sinoaortic denervation (SAD).
      DESIGN AND METHODS: Rats were examined at different times after SAD or sham
      operation (Sham). Hemodynamics were recorded continuously in conscious
      unrestrained rats. The time course of hemodynamic changes and cardiovascular
      hypertrophy was observed and linear regression analysis was performed to study
      the role of hemodynamics in SAD-induced aortic and left ventricular hypertrophy.
      Long-term mortality, water and food intake, and body weight were also determined
      after operation. RESULTS: High mortality (40%), dramatic reduction of water and
      food intake, and weight loss occurred within 1 week after SAD. Chronic SAD rats
      exhibited a marked increase in blood pressure variability (BPV), with no change
      in the average level of blood pressure (BP), as compared with the Sham control
      rats. Increased BPV was higher at 2 weeks (about threefold) than 16 weeks (about
      twofold) after SAD. Aortic hypertrophy existed in all three kinds of examined
      rats: 2-, 10- and 16-week SAD rats. Left ventricular hypertrophy was found only
      in 10- and 16-week SAD rats. Both aortic hypertrophy and left ventricular
      hypertrophy were significantly and positively correlated with BPV, but not with
      BP level. CONCLUSION: Persistent high BPV following SAD can lead to aortic and
      left ventricular hypertrophy. The aorta is more sensitive to increased BPV than
      the heart.

PMID- 12195129
TI  - Effects of losartan and atenolol on left ventricular mass and neurohormonal
      profile in patients with essential hypertension and left ventricular hypertrophy.
AB  - OBJECTIVE: To compare the effects of the angiotensin II antagonist, losartan,
      with those of atenolol on left ventricular hypertrophy (LVH), blood pressure and
      neurohormone concentrations in hypertensive patients with LVH. DESIGN: A
      multinational, randomized, double-blind trial. SETTING: Hospital. PATIENTS:
      Hypertensive patients with an echocardiographically documented left ventricular
      mass index (LVMI) 120 g/m(2) (men) or 105 g/m(2) (women). INTERVENTIONS: Patients
      allocated randomly to groups received either losartan or atenolol 50 mg/day for
      36 weeks, with possible titration to 100 mg/day, and addition of
      hydrochlorothiazide 12.5 or 25 mg/day. MAIN OUTCOME MEASURES: Changes in LVMI and
      sitting systolic (SBP) and diastolic (DBP) blood pressures after 36 weeks of
      treatment (study powered for non-inferiority hypothesis). All echocardiographic
      data were read in a central laboratory by staff blinded to the treatments and
      sequence of echocardiographic tapes. RESULTS: The estimated treatment difference
      between the losartan and atenolol regimens (mean change from baseline at week 36)
      in LVMI was -2.5 g/m(2) [95% confidence interval (CI) -7.36 to 2.37 g/m(2) ] in
      favor of losartan, indicating that losartan was significantly non-inferior (
      0.001, non-inferiority limit 8 g/m(2) ) and numerically superior to atenolol in
      reducing LVMI. The losartan-based regimen significantly reduced LVMI after 36
      weeks compared with baseline (-6.56 g/m(2) , 95% CI -10.24 to -2.88 g/m(2) ,
      P<0.001), whereas the atenolol-based regimen had no significant effect (-3.71
      g/m, 95% CI -7.75 to 0.32 g/m(2) , P= NS). In a subset of 82 patients,
      significant changes in serum concentrations of atrial natriuretic peptide, brain
      natriuretic peptide and immunoreactive amino-terminal pro-brain natriuretic
      peptide were recorded in losartan-treated ( 0.01) but not atenolol-treated
      patients. Losartan and atenolol significantly decreased SBP and DBP from baseline
      after 6, 12, 24 and 36 weeks. The changes from baseline in DBP were greater in
      the atenolol group at weeks 6 and 36 [difference -2.6 mmHg ( P= 0.016) at week
      36]. However, both treatment regimens achieved similar SBP/DBP values at week 36
      (141.1 +/- 12.8/86.8 +/- 8.2 mmHg for losartan and 141.4 +/- 17.2/85.0 +/- 10.1
      mmHg for atenolol, respectively). Overall, losartan treatment was associated with
      significantly fewer drug-related clinical adverse events, compared with atenolol
      (10 and 22%, respectively, P= 0.028). CONCLUSIONS: Both losartan- and atenolol
      based regimens effectively decreased blood pressure. Losartan was non-inferior
      and numerically superior to atenolol in regression of LVH. The reduction in
      hypertrophy with losartan treatment was accompanied by reductions in circulating
      concentrations of cardiac natriuretic peptides. Losartan, by specifically
      blocking angiotensin II, may therefore have effects on the heart beyond those
      expected from the decrease in blood pressure alone. Losartan was better tolerated
      than atenolol.

PMID- 12195131
TI  - Effect of orlistat-induced weight loss on blood pressure and heart rate in obese
      patients with hypertension.
AB  - OBJECTIVE: To investigate the effects of long-term weight management with
      orlistat on blood pressure in obese hypertensive patients. DESIGN: A meta
      analysis of data from five multicenter, randomized, placebo-controlled studies,
      conducted in Europe and the USA, was performed. PATIENTS: Obese adults [body mass
      index (BMI) 28-43 kg/m(2) ] with uncontrolled diastolic hypertension or isolated
      systolic hypertension (ISH) were eligible for inclusion. INTERVENTIONS: Following
      a 4-week placebo lead-in period, patients were randomized to orlistat 120 mg or
      placebo three times daily, in conjunction with a mildly reduced calorie diet for
      1 year. MAIN OUTCOME MEASURES: Change in body weight was the primary efficacy
      parameter. Blood pressure, heart rate and systolic workload were assessed as
      secondary efficacy parameters. RESULTS: A total of 628 patients were included in
      the intent-to-treat (ITT) analysis. After 56 weeks, orlistat-treated patients had
      lost significantly more body weight than placebo recipients (8.0 versus 4.0%;
      P<0.001). Among patients with ISH, mean systolic pressure was reduced to a
      significantly greater degree after 1 year with orlistat compared to placebo (-9.4
      versus -4.6 mmHg; P= 0.022). Similarly, reductions in mean diastolic pressure in
      patients with diastolic hypertension were greater with orlistat than with placebo
      (-7.7 versus -5.6 mmHg; P= 0.017). Weight loss of >or= 10% was associated with
      significant reductions in blood pressure, heart rate and systolic workload.
      CONCLUSIONS: Orlistat promotes clinically meaningful weight loss that is
      associated with significant reductions in blood pressure and heart rate, and may
      therefore have a role in the management of hypertension in overweight and obese
      patients.

PMID- 12195133
TI  - Does brief-pulse ECT cause persistent or permanent memory impairment?

PMID- 12195132
TI  - Risk of new-onset diabetes in the Losartan Intervention For Endpoint reduction in
      hypertension study.
AB  - BACKGROUND: There has been uncertainty about the risk of new-onset diabetes in
      hypertensive individuals treated with different blood pressure-decreasing drugs.
      OBJECTIVES: To study this risk in hypertensive individuals who were at risk of
      developing diabetes mellitus in the Losartan Intervention For Endpoint reduction
      in hypertension (LIFE) study. METHODS: In the LIFE study, with a double-masked,
      randomized, parallel-group design, 9193 patients (46% men) with hypertension
      (mean age 67 years, average pressure 174/98 mmHg after placebo run-in) and
      electrocardiogram-documented left ventricular hypertrophy were randomly assigned
      to once-daily losartan- or atenolol-based antihypertensive treatment and followed
      for at least 4 years (mean 4.8 years). At baseline, 7998 patients did not have
      diabetes mellitus and were thus at risk of developing this condition during the
      study. To demonstrate ability to predict new-onset diabetes, we developed a
      prediction score using the significant variables from multivariate analyses
      (serum glucose, body mass index, serum high-density lipoprotein cholesterol,
      systolic blood pressure and history of prior use of antihypertensive drugs).
      RESULTS: There was a steadily increasing risk of diabetes with increasing level
      of-risk score; patients in the highest quartile were at considerably greater risk
      than those in the three lower ones. Treatment with losartan was associated with
      lower risk of development of diabetes within each of the four quartiles of the
      risk score. As previously reported, new-onset diabetes mellitus occurred in 242
      patients receiving losartan (13.0 per 1000 person-years) and 320 receiving
      atenolol (17.5 per 1000 person-years); relative risk 0.75 (95% confidence
      interval 0.63 to 0.88; P<0.001). CONCLUSIONS: New-onset diabetes could be
      strongly predicted by a newly developed risk score using baseline serum glucose
      concentration (non-fasting), body mass index, serum high-density lipoprotein
      cholesterol concentration, systolic blood pressure and history of prior use of
      antihypertensive drugs. Independently of these risk factors, fewer hypertensive
      patients with left ventricular hypertrophy developed diabetes mellitus if they
      were treated with losartan than if they were treated with atenolol.

PMID- 12195134
TI  - Proxy validation of patient self-reports of ADL and IADL function before and
      after electroconvulsive therapy.
AB  - OBJECTIVE: To determine whether electroconvulsive therapy (ECT) patients' self
      reported functional status is similar to that reported by a proxy. BACKGROUND:
      Increasing levels of depression are associated with deteriorating functional
      status as reflected in the Instrumental Activities of Daily Living (IADL) scale.
      Depressed patients referred for ECT have poorer IADL status compared with
      depressed patients receiving medications, suggesting that IADL status may shape
      physicians' decision to recommend ECT ( 1). Further, IADL status improves with
      treatment of depression, both in ECT-and medication-treated patients. Given the
      potential importance of IADL status for ECT patients, we examined whether IADL
      status as reported by patients prior to ECT was comparable to IADL status as
      described by a proxy. DESIGN/METHODS: Forty depressed patients (23 men and 17
      women, mean age 58.1 +/- 17.5) were each interviewed alone with the 21-item
      Hamilton Depression Rating Scale (HDRS), Mini-Mental State Exam (MMSE), an
      Activities of Daily Living (ADL) scale, and an IADL scale. We then privately
      interviewed a first-degree relative who lived with each patient and recorded
      their impression of the patient's ADL and IADL function before ECT, and at 2 and
      4 weeks after ECT. RESULTS: baseline scores for HDRS and MMSE were consistent
      with a severe level of depressive symptoms and intact global cognitive function.
      Patients' and proxies' IADL scores were highly correlated before ECT, 2 weeks
      after ECT, and 4 weeks after ECT. Significant, but slightly weaker correlations
      were seen for ADL scores. CONCLUSIONS: Ideally, ADL and IADL function would be
      measured by direct observation rather than either patient or proxy report. At
      this time it is unknown whether the patient or the proxy report should be
      considered the "gold standard." In this study, the patients' self-reported
      functional scores were highly correlated with the proxies' scores. We conclude
      that patients' reports of their function are roughly comparable to proxies'
      impressions before and after ECT.

PMID- 12195135
TI  - High but not low ECS stimulus intensity augments apomorphine-stimulated dopamine
      postsynaptic receptor functioning in rats.
AB  - BACKGROUND: Clinical research shows that the antidepressant and cognitive adverse
      effects of electroconvulsive therapy are both dependent on the administered
      electrical stimulus intensity (dose); however, dose-dependent neurotransmitter
      system changes in the brain, which might underlie the therapeutic or adverse
      effects, remain to be demonstrated. OBJECTIVE: We used a behavioral model to
      examine dose-related effects of electroconvulsive shock (ECS) on dopamine
      postsynaptic receptor functioning in the rat brain. METHODS: In a factorially
      designed study, rats (n = 100) were treated with five once-daily ECSs at three
      levels (sham ECS, 30 mC ECS, and 120 mC ECS), and with drug at two levels
      (saline, and 1 mg/kg s.c. apomorphine). Motility was assessed in the small open
      field. RESULTS: Apomorphine-elicited, dopamine postsynaptic receptor-mediated
      hypermotility was significantly increased by 120 mC ECS but not by 30 mC ECS. An
      additional but unrelated finding was that, while the ECS seizure duration
      expectedly decreased across time, no dose-dependent effects were observed.
      CONCLUSION: ECS-induced dopamine postsynaptic receptor up-regulation may depend
      on the intensity of the administered electrical stimulus.

PMID- 12195136
TI  - A dental risk management protocol for electroconvulsive therapy.
AB  - This article describes the results of an evaluation of a system to use trained
      junior psychiatric doctors to perform the pre-ECT oral assessment. All junior
      doctors were given a 1-hour training session in making oral assessments, and
      their ability to diagnose was tested by dental follow-up visits to patients they
      had assessed. Seventy-one patients were seen by both doctor and dentist, and the
      sensitivity for doctors ranged between 92% for the presence of dentures or
      removable bridges to 8% for the presence of teeth vulnerable to fracture. Where
      the doctors made a positive diagnosis, these were not always correct; the
      positive predictive value ranging from 92% for dentures or removable bridges to
      25% for teeth vulnerable to fracture. It is concluded that the use of trained
      doctors is better than no assessment but falls short of that provided by a
      dentist with experience of psychiatric patients undergoing ECT.

PMID- 12195137
TI  - Efficacy of electroconvulsive therapy combined with antipsychotic medication in
      treatment-resistant schizophrenia: a prospective, open trial.
AB  - This study examined the short-term efficacy of electroconvulsive therapy (ECT)
      combined with antipsychotic medication in treatment-resistant schizophrenia
      (TRS). Fifteen patients with TRS from an in-patient psychiatric rehabilitation
      unit participated. Patients completed a course of ECT consisting of 8 to 20
      sessions, while their antipsychotic medications were continued throughout the
      study. Patients were assessed at baseline, 1 week, 1 month, and 2 months after
      their last ECT session. Assessment instruments included the Brief Psychiatric
      Rating Scale (BPRS), Hamilton Depression Rating Scale, Scale for the Assessment
      of Negative Symptoms (SANS), Global Assessment Scale (GAS), Clinical Global
      Impression (CGI), Nurses' Observation Scale for In-Patient Evaluation, and
      occupational therapists' rating of the patients' functioning with respect to
      work, social, and leisure activities. Compared with the baseline assessment, at
      each posttreatment evaluation, patients showed statistically significant
      improvement in the GAS and CGI. In addition, they were significantly better in
      terms of BPRS and SANS scores, as well as work performance and social functioning
      at the 2-month post-ECT evaluation.

PMID- 12195138
TI  - ECT treatment of malignant catatonia/NMS in an adolescent: a useful lesson in
      delayed diagnosis and treatment.
AB  - A 17-year-old adolescent female presented to a psychiatric emergency room with
      excitement, confusion, and psychotic symptoms. After brief exposure to
      haloperidol and olanzapine, she developed fever, rigidity, waxy flexibility,
      autonomic instability, and elevated creatinine phosphokinase enzyme.
      Approximately 6 weeks after the onset of the illness, multiple laboratory tests,
      and evaluation at three different hospitals, the condition was effectively
      treated with electroconvulsive therapy (ECT). This case is a lesson in delayed
      recognition and the delayed use of ECT for the malignant catatonia/neuroleptic
      malignant syndrome.

PMID- 12195139
TI  - Successful ECT in a patient with intracranial venous angioma.
AB  - The 1990 American Psychiatric Association (APA) Task Force report on
      electroconvulsive therapy (ECT) suggests that there is an increased risk of
      complications in patients with intracranial vascular masses. There have been only
      a few published reports on the use of ECT in these patients. In this case report,
      an additional case is described that used ECT in the treatment of major
      depression in a 72-year-old patient with a venous angioma involving the left
      cerebellum. Brain imaging studies, neurosurgery, cardiology, and orthopedic
      consultations were obtained prior to ECT. Blood pressure was monitored closely
      throughout the course of ECT. Prior to each ECT, antihypertensive medication was
      given in addition to other pretreatment medications. Consistent with previously
      published reports, the patient did not experience any neurological deterioration
      or adverse effects. A brief review of the literature on the use of ECT in
      patients with venous angioma and other intracranial vascular masses is presented.

PMID- 12195140
TI  - Postictal asystole during ECT.
AB  - BACKGROUND: Asystole is an uncommon but potentially fatal complication of
      electroconvulsive therapy (ECT). Several risks for poststimulus asystole have
      been described, but risks for asystole at other times have not. METHOD: Two
      instances of ECT postictal asystole in healthy adult males are reported. Features
      in common are identified. RESULTS: features shared differ from risk factors for
      poststimulus asystole. In common were adult but not geriatric age, male sex, good
      physical and cardiac health, mesomorphic habitus, anticholinergic pretreatment,
      vigorous ECT seizure, and low resting heart rate. Both patients showed postictal
      bradyarrhythmia at the previous ECT. CONCLUSIONS: Postictal asystole has apparent
      similarities to postexertional asystole in athletes. The combination of higher
      pretreatment doses of an atropinic agent, a sympatholytic agent, and close
      monitoring of postictal cardiac rhythm should be considered with patients similar
      to ours, especially after occurrence of postictal bradyarrhythmia.

PMID- 12195141
TI  - ECT literature: frequently cited papers and their impact on the field.

PMID- 12195142
TI  - Right unilateral and bifrontal electroconvulsive therapy in the treatment of
      depression: a preliminary study.

PMID- 12195143
TI  - Knowledge and attitudes regarding ECT.

PMID- 12195144
TI  - Electrotherapeutics.

PMID- 12195145
TI  - An attitude towards learning.

PMID- 12195146
TI  - Photodynamic therapy for Barrett's esophagus and high grade dysplasia: results of
      a patient satisfaction survey.
AB  - There are few data available describing the experience of patients who have
      undergone photodynamic therapy with porfimer sodium for Barrett's esophagus. We
      describe the results of a satisfaction survey reported by 16 of 18 patients (11
      men, 5 women; median age 75 years; median response at 27 months after treatment)
      treated with photodynamic therapy for Barrett's esophagus with high-grade
      dysplasia. Treatments were performed on an outpatient basis although two patients
      required clinic visits for intravenous fluids. Subjects reported their most
      significant post-treatment problem was odynophagia or dysphagia (75%), which was
      best treated with a hydrocodone bitartrate and acetaminophen elixir (75%).
      Cutaneous photosensitivity persisted for a median of six weeks; two patients had
      phototoxic reactions requiring clinic evaluation and treatment. All but two
      patients reported swallowing problems lasting a median of four weeks, and weight
      loss (median 6.8 kg). All patients indicated they would again choose photodynamic
      therapy if they were faced with a similar choice of endoscopic treatment versus
      surgery for Barrett's esophagus with high-grade dysplasia. These results indicate
      a generally high level of satisfaction in patients who have been treated with
      porfimer sodium photodynamic therapy for Barrett's esophagus with high-grade
      dysplasia.

PMID- 12195147
TI  - Flexible endoscopes: structure and function: the endoscopic retrograde
      cholangiopancreatography elevator system.
AB  - Flexible endoscopes are complex medical instruments that are easily damaged. In
      order to maintain the flexible endoscope in optimum working condition, the user
      must have a thorough understanding of the structure and function of the
      instrument. This is the fourth in a series of articles presenting an in-depth
      look at the care and handling of the flexible endoscope. The first three articles
      discussed the air-water system, the suction channel system, and the mechanical
      system. This article will focus specifically on the endoscopic retrograde
      cholangiopancreatography elevator system.

PMID- 12195148
TI  - Patients' experiences of their intake of food and fluid following gastrectomy due
      to tumor.
AB  - Several studies have documented patients' intake of parenteral and enteral
      nutrition following gastrointestinal surgery. There is a lack of knowledge,
      however, regarding patients' experiences of intake of food and fluid following
      gastrointestinal surgery. The aim of this study was to describe patients'
      experiences of their appetite, hunger, changes in weight, and intake of food and
      fluid three months after gastrointestinal surgery due to tumor. Fifteen patients
      were invited to be interviewed regarding their experiences following
      gastrointestinal surgery due to tumor. The method used for data analysis was a
      qualitative content analyses approach. The categorization of data identified
      three themes: 1) the struggle to eat and drink; 2) bodily estrangement; and 3)
      nutritional treatment regimens. These three themes consisted of subthemes such
      as: lack of appetite and hunger; difficulties in eating and drinking; feelings of
      nausea; and fighting and adaptation. The findings contribute to a deeper
      understanding of these patients' nutritional regimen and suggest the individual's
      personal situation and living circumstances should be considered when developing
      a nutritional plan following gastrointestinal surgery for tumor.

PMID- 12195150
TI  - "Diss" stress before it distresses you.

PMID- 12195149
TI  - Understanding diabetic gastroparesis: a case study.
AB  - The purpose of this article is to present an overview of diabetic gastroparesis,
      defined as delayed gastric emptying in the absence of mechanical obstruction.
      Diabetic gastroparesis is a substantial and unrecognized problem. Failure to
      treat may result in a decreased quality of life and a potential increase for
      morbidity. The treatment protocol for diabetic gastroparesis combines dietary and
      pharmacologic measures. This article will discuss normal physiology of gastric
      emptying along with the pathogenesis of delayed emptying in patients with
      diabetes. Nursing implications for the care of the patient with diabetic
      gastroparesis is also presented along with commonly used pharmacologic agents.

PMID- 12195151
TI  - Legislative protection against mandatory overtime.

PMID- 12195152
TI  - GI journeys across the U.S.

PMID- 12195154
TI  - Ethics in research.

PMID- 12195155
TI  - Response to necessity for subspecialty certification in hepatology for nurses.

PMID- 12195157
TI  - Linkage between retinoid and fatty acid receptors: implications for breast cancer
      prevention.
AB  - Certain dietary retinoids and polyunsaturated fatty acids (PUFAs) consistently
      inhibit progression of mammary carcinogenesis both in animal studies and cell
      culture, but clinically, their effect is inconsistent. New evidence of
      synergistic interaction between the nuclear receptors for the two groups of
      nutritional agents suggests that appropriate selective ligands from each group
      might be combined in breast cancer chemoprevention studies. Peroxisome
      proliferator-activated receptor (PPAR) gamma is a nuclear receptor that is
      activated by PUFAs, eicosanoids and antidiabetic agents such as troglitazone.
      Such activation can cause growth inhibition in human mammary cancer cells in
      culture and the effect is enhanced by ligands of retinoic acid receptor (RAR) and
      retinoid X receptor (RXR). In mouse mammary tissue in organ culture, an RXR
      selective ligand has been shown to enhance the effect of troglitazone in
      suppressing carcinogen-induced pre-neoplastic changes. A PPAR/RXR heterodimer is
      involved in tumour growth inhibition and has been shown to bind directly to
      nuclear oestrogen response elements (ERE) independently of oestrogen receptor
      (ER) activity. A combination of an RXR-selective retinoid with either
      troglitazone or else a long-chain n-3 PUFA, is proposed for a short-term study in
      postmenopausal women after primary surgery for intraductal breast cancer. The
      resulting activation of PPAR/RXR expression may increase response to retinoid
      administration, especially in the presence of obesity and insulin resistance,
      because of the ability of PPAR gamma ligands to reduce insulin-like growth factor
      I (IGF-I) concentrations. Serial core biopsies of breast tissue over a short term
      are proposed to identify changes in phenotype, which may influence progression to
      invasiveness. In addition to cytomorphological criteria, expression of ER alpha
      and beta, RAR alpha and beta, and IGF-I receptor in the nucleus should be
      examined.

PMID- 12195156
TI  - Epidemiology of male breast cancer.

PMID- 12195158
TI  - Familial risk factors for breast cancer among Arab women in Israel.
AB  - The incidence of breast cancer in Arab women is low compared with western
      populations in other countries. Very few studies on risk factors for breast
      cancer in Arab women have been reported. The aim of the present study was to
      evaluate familial risk factors for breast cancer among Arab women in Israel. A
      case-control study was carried out on 72 Arab women diagnosed with breast cancer
      and 140 healthy controls. Cases were identified through oncology wards and
      controls were sampled from community and hospital out-patient clinics. All
      participants were interviewed and information obtained on family history of
      breast cancer and other cancers, and other potential risk factors. Eight women
      with breast cancer and five women without breast cancer had a first-degree
      relative with breast cancer. The odds ratio for breast cancer for a woman with a
      first-degree relative with breast cancer was 3.4 (95% confidence interval (CI)
      1.06-10.7, P = 0.04). The odds ratio for Muslim women with a first-degree
      relative with breast cancer was higher than that for Christian women (6.07 and
      1.53, respectively). Family history of breast cancer was a risk factor for breast
      cancer in Arab women. The estimated relative risk associated with an affected
      first-degree relative was generally higher than that reported from other
      populations.

PMID- 12195159
TI  - Sunbed use at home: risk behaviour and psychosocial determinants.
AB  - The objective of this study was to analyse the behaviour of people with regard to
      sunbed use at home, and to analyse the psychosocial determinants of intention and
      behaviour with regard to limiting the health risk of using sunbeds at home. Data
      were collected by means of a telephone survey among 349 adults from the Dutch
      general public who use sunbeds at home (response=95%). Determinants that were
      assessed were: attitude with respect to safer use and the use of sunbeds in
      general, the social influences people encounter to use sunbeds in a safer way,
      and the self-efficacy expectations people have of their ability to use sunbeds
      more safely. The results showed that there were great differences between
      people's perceptions of their safe sunbed behaviour, and their actual safety
      behaviour. Almost all respondents (94%) thought that their sunbed behaviour was
      safe, while in reality only 37% of the respondents used the sunbed in accordance
      with the safety guidelines. The safer users of sunbeds differed on many
      determinants from the unsafe users. Intention to minimize the health risk when
      using sunbeds could be predicted by a person's perceived self-efficacy, the
      overall attitude and anticipated regret beliefs (R2=0.52). Sunbed users should be
      made aware of their risk behaviour with regard to sunbeds as well as providing
      information on changing determinants, in order to positively change people's
      intentions and behaviour with regard to the safer use of sunbeds.

PMID- 12195160
TI  - Endothelial nitric oxide synthase gene polymorphisms and genetic susceptibility
      to prostate cancer.
AB  - The endothelial cell-specific form of nitric oxide synthases (ecNOS) is localized
      at 7q35-q36 and is involved in vascular development and tumour growth in human
      prostate cancer. We have conducted a case-control study to investigate the
      prevalence of two polymorphisms at intron 4 (ecNOS4a/b) and exon 7 (Glu-Asp298)
      of ecNOS gene in 125 prostate cancer (PCa) patients and in 153 controls. We
      observed that the a-allele (aa or ab genotypes from ecNOS4a/b) was over-presented
      in the group of PCa with Gleason histological grade >or=7 (P=0.041). With regard
      to the Glu-Asp298 polymorphism, patients with the T-allele were younger than
      patients with no T-allele (P=0.037), and a statistically significant difference
      was noted in the Glu-Asp298 genotype distribution between cases with advanced
      disease and cases with localized disease (P=0.0013). When comparing cases and
      controls with logistic regression analysis we observed that the presence of the a
      allele is associated with prostate cancer risk (odds ratio (OR) 1.83; 95%
      confidence interval (CI) 1.06-3.17; P=0.029), to high histological grade (Gleason
      >or=7) of PCa (OR 2.18; 95% CI 0.95-4.98; P=0.062) and with the risk of
      progression of the cancer disease (OR 2.85; 95% CI 1.19-6.82; P=0.018).
      Furthermore, we found that carriers with the combination of the a-allele (aa and
      ab ecNOS4a/b genotypes) and T-allele (GT and TT from Glu-Asp298) have a threefold
      increase in prostate cancer risk (OR 3.13; 95% CI 1.41-6.91, P=0.004). In
      summary, we have identified an NO-related genetic risk factor for prostate cancer
      that may help in understanding the molecular mechanism involved in the individual
      susceptibility to prostate cancer.

PMID- 12195161
TI  - Cancer chemoprevention by hydroxytyrosol isolated from virgin olive oil through
      G1 cell cycle arrest and apoptosis.
AB  - Recent epidemiological evidence and animal studies suggest a relationship between
      the intake of olive oil and a reduced risk of several malignancies. The present
      study assesses the effect of hydroxytyrosol, a major antioxidant compound of
      virgin olive oil, on proliferation, apoptosis and cell cycle of tumour cells.
      Hydroxytyrosol inhibited proliferation of both human promyelocytic leukaemia
      cells HL60 and colon adenocarcinoma cells HT29 and HT29 clone 19A. The con
      centrations of hydroxytyrosol which inhibited 50% of cell proliferation were
      approximately 50 and approximately 750 micromol/l for HL60 and both HT29 and HT29
      clone 19A cells, respectively. At concentrations ranging from 50 to 100
      micromol/l, hydroxytyrosol induced an appreciable apoptosis in HL60 cells after
      24 h of incubation as evidenced by flow cytometry, fluorescence microscopy and
      internucleosomal DNA fragmentation. Interestingly, no effect on apoptosis was
      observed after similar treatment of freshly isolated human lymphocytes and
      polymorphonuclear cells. The DNA cell cycle analysis, quantified by flow
      cytometry, showed that the treatment of HL60 cells with hydroxytyrosol 50-100
      micromol/l arrested the cells in the G0/G1 phase with a concomitant decrease in
      the cell percentage in the S and G2/M phases. These results support the
      hypothesis that hydroxytyrosol may exert a protective activity against cancer by
      arresting the cell cycle and inducing apoptosis in tumour cells, and suggest that
      hydroxytyrosol, an important component of virgin olive oil, may be responsible
      for its anticancer activity.

PMID- 12195162
TI  - Validity of breast cancer in the Danish Cancer Registry. A study based on
      clinical records from one county in Denmark.
AB  - Cancer registries are essential in order to monitor the incidence of cancer and,
      with proper follow-up, survival in a population. However, the usefulness of the
      registry depends upon the data quality. To validate the Danish Cancer Registry
      concerning breast cancer in female residents of Aarhus county 1983-1989, registry
      records were compared with clinical records. Completeness was validated in 2062
      patients and correctness was determined for pathologically proven primary
      invasive breast cancer in 1949 patients. Incidence data were complete with no
      tumours missing. Data were coded according to ICD-7 and correctness of registry
      data in terms of basis of diagnosis and tumour malignancy was 99%. Information on
      extent of disease (stage) was not complete and there was a high disconcordance,
      in particular for bilateral breast tumours and cases with distant metastasis.
      Even crude staging into local and regional disease was inconsistent for 13% of
      cases, which probably hampered survival analysis by stage. The quality of
      registry data should be addressed when using variables, such as stage, not
      routinely reported by registries.

PMID- 12195163
TI  - Diet and gallbladder cancer: a case-control study.
AB  - Cancer of the gallbladder is rare but fatal, and has an unusual geographic and
      demographic distribution. Gallstones and obesity have been suggested as possible
      risk factors. As diet is known to influence both these factors, we carried out
      the present study to evaluate the possible role of diet in gallbladder
      carcinogenesis. A case-control study involving 64 newly diagnosed cases of
      gallbladder cancer and 101 cases of gallstones was carried out. The dietary
      evaluation was carried out by the dietary recall method based on a preset
      questionnaire developed specifically for the present study, keeping in mind the
      common dietary habits prevailing in this part of the world. Odds ratios (OR) and
      95% confidence interval (CI) were calculated for various dietary items. A
      significant reduction in odds ratio was seen with the consumption of radish (OR
      0.4; 95% CI 0.17-0.94), green chilli (OR 0.45; 95% CI 0.21-0.94) and sweet potato
      (OR 0.33; 95% CI 0.13-0.83) among vegetables, and mango (OR 0.4; 95% CI 0.16
      0.99), orange (OR; 0.45; 95% CI 0.22-0.93), melon (OR 0.3; 95% CI 0.14-0.64) and
      papaya (OR 0.44; 95% 0.2-0.64) among fruits. A reduction in odds was also seen
      with the consumption of cruciferous vegetables, beans, onion and turnip, however
      the difference was not statistically significant. On the other hand, an increase
      in the odds was observed with consumption of capsicum (OR 2.2), beef (OR 2.58),
      tea (OR 1.98), red chilli (OR 1.29) and mutton (OR 1.2), however the difference
      was statistically not significant. In conclusion, the results of the present
      study show a protective effect of vegetables and fruits on gallbladder
      carcinogenesis, but red meat (beef and mutton) was found to be associated with
      increased risk of gallbladder cancer.

PMID- 12195164
TI  - Plant foods and differences between colon and rectal cancers.
AB  - A case-control study on plant food intake and its role in the risk of colon and
      rectal cancers was carried out in Montevideo, Uruguay. Four hundred and eighty
      four (484) cases of colorectal cancer and 1452 controls were frequency matched on
      age, sex, residence and urban/rural status. Among cases, 260 patients had colon
      cancer whereas 224 had rectal tumours. Controls had non-neoplastic conditions.
      Both cases and controls were interviewed in the four major hospitals in
      Montevideo shortly after admittance for diagnosis or treatment. The questionnaire
      included a section on frequency of foods, which included 64 items, in particular,
      queries on 18 vegetables, 10 fruits and 6 cereal dishes were included. Thus, the
      amount of plant foods consumed was complete and included the main plant foods in
      the Uruguayan diet. The analysis showed that rectal cancer displayed inverse
      associations with total plant foods, total vegetables, cooked vegetables,
      potatoes and legumes. When data were stratified by tumour site and sex, only men
      showed a protective effect of plant foods (odds ratio (OR) of rectal cancer for
      men 0.4, 95% confidence interval (CI) 0.2-0.7). In contrast, women with rectal
      carcinoma were not associated with plant food intake. It can be concluded that
      plant foods are protective factors for men afflicted with colorectal cancer but
      that plant food intake is not associated with risk in women. This is, at least in
      part, due to the high risk associated with bread intake in this gender.

PMID- 12195165
TI  - Cellular and cordless telephones and the risk for brain tumours.
AB  - Microwave exposure from the use of cellular telephones has been discussed in
      recent years as a potential risk factor for brain tumours. We included in a case
      control study 1617 patients aged 20-80 years of both sexes with brain tumour
      diagnosed between 1 January 1997 and 30 June 2000. They were alive at the study
      time and had histopathologically verified brain tumour. One matched control to
      each case was selected from the Swedish Population Register. The study area was
      the Uppsala-Orebro, Stockholm, Linkoping and Goteborg medical regions of Sweden.
      Exposure was assessed by a questionnaire that was answered by 1429 (88%) cases
      and 1470 (91%) controls. In total, use of analogue cellular telephones gave an
      increased risk with an odds ratio (OR) of 1.3 (95% confidence interval (CI) 1.02
      1.6). With a tumour induction period of >10 years the risk increased further: OR
      1.8 (95% CI 1.1-2.9). No clear association was found for digital or cordless
      telephones. With regard to the anatomical area of the tumour and exposure to
      microwaves, the risk was increased for tumours located in the temporal area on
      the same side of the brain that was used during phone calls; for analogue
      cellular telephones the OR was 2.5 (95% CI 1.3-4.9). Use of a telephone on the
      opposite side of the brain was not associated with an increased risk for brain
      tumours. With regard to different tumour types, the highest risk was for acoustic
      neurinoma (OR 3.5, 95% CI 1.8-6.8) among analogue cellular telephone users.

PMID- 12195166
TI  - Time trends in cancer incidence and mortality in central Italy.
AB  - Time trends in cancer incidence and mortality represent an essential tool for
      monitoring the changes in population lifestyle and in the environmental risks and
      the effectiveness of the health system on cancer control in a specific area.
      During 1985-1997 82 506 malignant tumours were diagnosed in the Tuscany Cancer
      Registry, central Italy (about 1 200 000 inhabitants) and 54 979 cancer deaths
      registered in the period 1985-1999 by the Regional Mortality Registry were
      analysed. A statistically significant decrease in incidence was evidenced for
      stomach and gallbladder in both sexes, and for oesophagus, larynx and lung among
      males. Significant increases were documented for melanomas of the skin, kidney
      and non-Hodgkin's lymphoma in both sexes for colon, prostate and Kaposi's sarcoma
      among males and for breast, thyroid and multiple myeloma among females. Mortality
      decreased significantly for stomach and thyroid in both sexes and for oral cavity
      and pharynx, oesophagus, rectum, larynx, lung, bone, prostate, testis and
      Hodgkin's disease among males and colon, gallbladder and breast among females.
      Mortality increased for soft tissue, brain and multiple myeloma. In conclusion,
      most of these data can be explained as the effect of the modifications that
      occurred in smoking habits between the sexes and as the consequence of the
      primary and secondary prevention activities that are ongoing in the area.

PMID- 12195167
TI  - 'Children under the Sun'-- UV radiation and children's skin. WHO Workshop --
      Children's sun protection education.

PMID- 12195168
TI  - A multi-center, double blind clinical trial comparing benefit from three commonly
      used hearing aid circuits.
AB  - OBJECTIVE: Although numerous studies have demonstrated that hearing aids provide
      significant benefit, carefully controlled, multi-center clinical trials have not
      been conducted. A multi-center clinical trial was conducted to compare the
      efficacy of three commonly used hearing aid circuits: peak clipping, compression
      limiting, and wide dynamic range compression. DESIGN: Patients (N = 360) with
      bilateral, sensorineural hearing loss were studied using a double blind, three
      period, three-treatment crossover design. The patients were fit with each of
      three programmable hearing aid circuits. Outcome tests were administered in the
      unaided condition at baseline and then after 3 mo usage of each circuit, the
      tests were administered in both aided and unaided conditions. The outcome test
      battery included tests of speech recognition, sound quality and subjective scales
      of hearing aid benefit, including patients' overall rank-order rating of the
      three circuits. RESULTS: Each hearing aid circuit improved speech recognition
      markedly, with greater improvement observed for soft and conversationally loud
      speech in both quiet and noisy listening conditions. In addition, a significant
      reduction in the problems encountered in communication was observed. Some tests
      suggested that the two compression hearing aids provided a better listening
      experience than the peak clipping hearing aid. In the rank-order ratings,
      patients preferred the compression limiting hearing aid more frequently than the
      other two hearing aids. CONCLUSIONS: The three hearing aid circuits studied
      provide significant benefit both in quiet and in noisy listening situations. The
      two compression hearing aids appear to provide superior benefits compared to the
      linear circuit, although the differences between the hearing aids were smaller
      than the differences between unaided and aided conditions.

PMID- 12195169
TI  - Organization and administration of the NIDCD/VA Hearing Aid Clinical Trial.
AB  - This article describes the organization and administration of the NIDCD/VA
      Hearing Aid Clinical Trial. The trial involved a total of 360 patients with
      bilateral, sensorineural hearing loss from eight VA Medical Centers to study
      three different hearing aid circuits in a three-period, three-treatment crossover
      design. Strong central coordination of such a complex multi-center clinical trial
      is essential to its success. The trial took more than 5 years to design,
      implement, and complete. This timeline is also described.

PMID- 12195170
TI  - Speech recognition performance of patients with sensorineural hearing loss under
      unaided and aided conditions using linear and compression hearing AIDS.
AB  - OBJECTIVES: This study compared speech recognition performance on the
      Northwestern University Auditory Test No. 6 (NU-6) and the Connected Speech Test
      (CST) for three hearing aid circuits (peak clipping [PC], compression limiting
      [CL], and wide dynamic range compression [WDRC]) in adults with symmetrical
      sensorineural hearing loss. The study also questioned whether or not hearing aid
      benefit for the three circuits was dependent upon the speech level and the signal
      to-babble ratio (S/B) and upon the degree and slope of hearing loss. DESIGN:
      Unaided speech recognition performance for NU-6 and CST materials presented from
      a loudspeaker at 0 degrees was measured during Visit 1, and both unaided and
      aided performance was measured at 3-mo intervals during Visits 2 to 4. The NU-6
      was presented in quiet at a conversational speech level of 62 dB SPL. The CST was
      presented in 10 listening conditions-three S/B (-3, 0, and 3 dB) at each of three
      speech levels (soft speech at 52 dB SPL, conversational speech at 62 dB SPL, and
      loud speech at 74 dB SPL) and in quiet at 74 dB SPL. Uncorrelated multi-talker
      babble was presented from two loudspeakers at 45 degrees on each side of the main
      speaker. Hearing aid benefit was examined for 360 subjects divided into four
      groups of hearing loss, pure tone average <40 dB HL and slope <10 dB/octave or
      >10 dB/octave and hearing loss >40 dB HL for the two slope categories. RESULTS:
      Hearing aid benefit (aided minus unaided performance) measured on the NU-6 in
      quiet exceeded 31 rau for all three circuits. Although small statistical
      advantages were found for the WDRC, the differences were approximately 2% and are
      not considered clinically relevant. Unaided CST performance showed a complex
      relationship between presentation level and signal-to-babble ratio that was
      further confounded by the degree of hearing loss. For the two mild hearing loss
      groups and for each of the three nominal signal-to-babble ratios, CST performance
      decreased by 20 rau for the -3 dB S/B to 6 rau for the 3 dB S/B as speech level
      increased from 52 to 74 dB SPL. In contrast, unaided performance increased by 32
      to 13 rau with signal level for all signal-to-babble ratios for the two >40 dB
      hearing loss groups. Overall, aided CST performance exceeded unaided performance
      for all 10 conditions. As expected, hearing aid benefit was greatest (27 rau) for
      soft speech and smallest for loud speech (6 rau). Differences among the hearing
      aid circuits were small with only one significant difference; the WDRC at 62/0
      was poorer by 3 rau than the other two circuits. When the CST data were analyzed
      as a function of hearing loss, five pair-wise comparisons were significant. In
      contrast to the unaided performance, aided performance for all hearing loss
      groups decreased as presentation level increased, even though the signal-to
      babble ratio was constant. CONCLUSIONS: All three hearing aids circuits provided
      benefit over the unaided condition in both quiet and noise. The greatest benefit
      was measured for soft speech in the more severe hearing loss groups. Although
      only small differences were measured among the three hearing aid circuits,
      significant differences favored the PC and CL circuits over the WDRC in the mild
      hearing loss groups and favored the WDRC over the PC in the more severe, sloping
      hearing loss group. An interesting interaction between speech level, signal-to
      babble ratio, degree of hearing loss, and amplification was found. For a constant
      signal-to-babble ratio, recognition performance decreased as speech level
      increased from 52 to 74 dB SPL. The effect was most marked in the milder hearing
      loss groups and in the aided conditions, and occurred at even the lowest speech
      levels.

PMID- 12195171
TI  - Quality rating test of hearing aid benefit in the NIDCD/VA Clinical Trial.
AB  - OBJECTIVE: As part of a large clinical trial that compared three hearing aid
      circuits using several evaluation methods, judgments about quality of listening
      experiences were sought from all subjects. Three dimensions were examined:
      loudness, noise interference and overall liking (quality). DESIGN: Eight
      Audiology units in VA Medical Centers participated. Three hearing aid circuits
      were compared: linear peak clipper, compression limiter, and wide dynamic range
      compressor. The experimental design was a three-period, three-treatment crossover
      design. Baseline measures were made using a battery of tests in unaided
      conditions. Subjects (N = 360) were then stratified by participating site and
      randomized to one of six sequences of the three hearing aid circuits. Each
      circuit was fit binaurally and all subjects used each of the three circuits for 3
      mo. All outcome measures were administered in unaided and aided conditions after
      each 3-mo period. The study used a double-blind strategy, i.e., neither the
      audiologist giving the tests nor the subject knew which circuit was being used. A
      different audiologist programmed the devices. RESULTS: For loudness judgments,
      soft and loud presentations of speech in quiet and in babble competition were
      judged more comfortable via the wide dynamic range circuit. The noise
      interference tasks and overall liking of the listening experience showed few
      significant differences across circuits. All circuits made the listening
      experience more comfortably loud for soft and conversation-level speech.
      CONCLUSIONS: Differences across circuits in terms of the overall quality of the
      listening experience and how noise interference was rated were small. Only
      isolated conditions, usually favoring the WDRC circuit, reached significance
      levels. The loudness dimension results were clearer. The WDRC circuit made sounds
      at either the loud or soft extreme more comfortable. When subjects were grouped
      by amount and configuration of hearing loss, the advantages for the WDRC and to a
      lesser extent the linear compression-limited circuit were clearest among subjects
      with mild hearing losses with a >10 dB/octave high-frequency drop, and those with
      moderate, relatively flat hearing losses.

PMID- 12195172
TI  - Subjective measures of hearing aid benefit in the NIDCD/VA Clinical Trial.
AB  - OBJECTIVE: Subjective measures of performance were assessed on three different
      hearing aid circuits as part of a large clinical trial. These measurements
      included the Profile of Hearing Aid Performance and a subjective ranking of
      individual preference. DESIGN: A multi-center, double-masked clinical trial of
      hearing aids was conducted at eight VA Medical Centers. Three hearing aid
      circuits, a linear peak-clipper, a linear compression limiter and a wide dynamic
      range compressor, were investigated. The experimental design was a three-period,
      three-treatment crossover design. Subjects (N = 360) were stratified by site and
      randomized to one of six sequences for the hearing aid circuits. All fittings
      were binaural and involved a 3-mo trial with each of the three circuits. All
      subjective measures were administered for unaided and aided conditions at the end
      of each trial period. RESULTS: While all of the circuits resulted in improved
      scores on the aided versus the unaided PHAP, there were few conditions in which
      one circuit outperformed the others. An exception was the aversiveness of sound
      subscale where the peak clipper frequently scored worse than either the
      compression limiter or the wide dynamic range compressor. In the subjective
      ranking scale the compression limiter received more first place rankings than the
      other two circuits, especially for one subgroup of patients with moderate flat
      hearing loss. CONCLUSIONS: All circuits were perceived as beneficial by these
      subjects in most situations. The peak clipper scored worse on aversiveness of
      sound than did the other two circuits for most subjects, while the compression
      limiter seemed to have a slight advantage in subjective rankings. Most subjects
      perceived considerable aided benefit in situations involving background noise and
      reverberation, situations where hearing aid benefit is often questioned.

PMID- 12195173
TI  - Coupler and real-ear measurement of hearing aid gain and output in the NIDCD/VA
      Hearing Aid Clinical Trial.
AB  - OBJECTIVE: Because the NIDCD/VA Hearing Aid Clinical Trial was conducted across
      eight clinical sites, rigorous control of the electroacoustic characteristics of
      the experimental devices was required. DESIGN: The parameters monitored included
      the gain and output of the approximately 720 hearing aids in the trial, measured
      both in the 2 cm3 coupler and in situ. Each measurement was repeated six times on
      each hearing aid across the 9-mo duration of the study to insure both the
      stability and the accuracy of the circuits under investigation. RESULTS: The gain
      data obtained in the coupler and in situ adequately demonstrated the stability of
      the instrument and the repeated measurements over time and across study sites.
      The output values produced by the experimental device also maintained acceptable
      constancy, both within and across treatment periods. CONCLUSIONS: These
      measurements reflected satisfactory stability and sufficient accuracy within the
      circuits to achieve the intended goals of the study.

PMID- 12195174
TI  - Aided perception of /s/ and /z/ by hearing-impaired children.
AB  - OBJECTIVE: The overall goal of this study was to determine the accuracy with
      which hearing-impaired children can detect the inflectional morphemes /s/ and /z/
      when listening to speech through hearing aids. DESIGN: In the first part of the
      study a perceptual test was developed with equal numbers of singular and plural
      nouns spoken by both a male and female talker. Thirty-six normal-hearing children
      (3 to 5 yr) were tested to determine the age at which children could perform this
      test without difficulty. In the second part of the study, 40 children with
      bilateral sensorineural hearing losses (5 to 13 yr) were tested while wearing
      personal hearing aids. Stimuli were presented in the sound field at 65 dB SPL.
      RESULTS: For the normal-hearing children, mean performance increased and inter
      subject variability decreased through age 5 yr 3 mo when performance reached
      >or=90% for all children. No significant talker or form (plural versus singular)
      effects were noted for this group. For the hearing-impaired children, performance
      varied considerably across all ages. For these subjects, significant effects of
      talker and form were observed. Specifically, plural test items spoken by the
      female talker showed the highest error rate. CONCLUSIONS: In general, mid
      frequency audibility (2 to 4 kHz) appeared to be most important for perception of
      the fricative noise for the male talker while a somewhat wider frequency range (2
      to 8 kHz) was important for the female talker.

PMID- 12195175
TI  - Tolerable hearing aid delays. II. Estimation of limits imposed during speech
      production.
AB  - OBJECTIVE: We used real-time processing in a wearable digital hearing aid to
      examine the effect of processing delay on normal-hearing participants while
      speaking. Objective and subjective data were recorded so as to permit analysis of
      both the production and perception of speech read aloud from a script. We also
      asked participants to rate the disturbance of the echo introduced by the delay.
      DESIGN: Thirty-two (16M, 16F) participants were fitted binaurally with behind-the
      ear (BTE) aids connected to a digital processor. A 4 mm Libby horn, surrounded by
      an expanding foam earplug, conducted processed sound into each ear canal. The
      processor provided either linear processing or three-channel, fast-acting wide
      dynamic range compression, independently to each ear. Insertion gains were set,
      using a KEMAR manikin, to be 0 dB over a wide frequency range, for frontally
      presented speech with a free field level of 65 dB SPL. Additionally, the aids
      introduced one of four selectable delays (7 to 43 msec) between the BTE
      microphone and receiver. After a short period of acclimatization, each
      participant read 16 prose passages of about 500 words in length in each of two
      similar-sized rooms with markedly different acoustics: reverberant and
      nonreverberant. For each passage, a subjective rating of the level of disturbance
      of the perceived echo was recorded, as well as simultaneous recordings from a
      microphone and a Laryngograph, which directly records glottal pulses. RESULTS:
      Disturbance ratings generally increased monotonically with increasing delay.
      Averaged results show that a delay between 25 and 30 msec is rated as
      "disturbing." Measures were also taken of word production rate, speech level and
      range of level as well as fundamental frequency and range of fundamental
      frequency. For these measures of speech production, there was no significant
      effect until the delay exceeded 30 msec. There was little effect of acoustic
      environment or aid processing (linear or compression). CONCLUSIONS: The
      acceptability of delays introduced by digital hearing aids is primarily
      determined by aspects of the perception of self-generated speech. Speech
      production, on average, is hardly affected unless the processing delay exceeds 30
      msec. The permissible limit of 20 to 30 msec is smaller than the delays at which
      audio-visual integration is disrupted.

PMID- 12195176
TI  - Frequency mapping in cochlear implants.
AB  - OBJECTIVE: To understand the short-term ("acute") effects of parametric
      variations to the frequency-to-electrode mapping on phoneme identification by
      Nucleus-22 cochlear implant listeners. METHODS: Phoneme recognition was measured
      in five Nucleus-22 cochlear implant listeners using custom four-channel
      continuous interleaved sampler (CIS) processors. For the four-channel processors,
      speech signals were band-pass filtered into four broad frequency bands. The
      temporal envelope in each band was extracted by half-wave rectification and low
      pass filtering at 160 Hz. The extracted envelope was then transformed to electric
      currents by a power function with an exponent of 0.2. The resulting electric
      currents were delivered to four electrode pairs (18,22), (13,17), (8,12), (3,7).
      The effect of frequency-to-electrode mapping was investigated by systematically
      varying the parameters of band-pass filters while fixing the electrode locations.
      Experiment 1 measured phoneme recognition as a function of the slope of band-pass
      filters. The slope of band-pass filters varied from 48 dB/octave to 6 dB/octave;
      the corner frequencies of band-pass filters were not varied. Experiment 2
      measured phoneme recognition as a function of the distribution of band-pass
      filters across a fixed overall frequency range. The frequency divisions of a
      fixed overall frequency range were systematically varied from a logarithmic to a
      linear distribution. Experiment 3 measured phoneme recognition as a function of
      the bandwidth of the band-pass filters. The bandwidth of each filter varied from
      0.2 to 2 octaves; the center frequencies for each band were not varied. No
      practice or feedback was provided for subjects in all experiments. RESULTS: The
      slope of the band-pass filters had little effect on both vowel and consonant
      recognition. A slight performance drop was observed for only the shallowest slope
      condition (6 dB/octave). In contrast, the distribution of the band-pass filters
      had a strong effect on vowel recognition but a weak effect on consonant
      recognition. Best performance was achieved when a logarithmic or near-logarithmic
      frequency distribution was used to divide the overall frequency range. The
      bandwidth of the band-pass filters had a moderate effect on both vowel and
      consonant recognition. Vowel scores dropped significantly when the bandwidth of
      filters was too broad, whereas consonant scores dropped significantly when a
      narrower bandwidth was used. CONCLUSION: Under "acute" testing conditions,
      phoneme recognition with a four-channel CIS strategy seems to be only mildly
      affected by the slope of the band-pass filters, but can be significantly affected
      by the distribution of filters as well as the bandwidth of the filters. Optimal
      or near-optimal performance can be achieved with a logarithmic frequency
      distribution. Vowels are more susceptible to broad bandwidths, whereas consonants
      are more susceptible to narrow bandwidths.

PMID- 12195177
TI  - Effects of hearing loss on echo thresholds.
AB  - OBJECTIVE: The purpose of this investigation was to determine the effects of
      hearing loss on the perception of echoes. DESIGN: Echo thresholds were measured
      for eight listeners with normal hearing and nine listeners with impaired hearing.
      Pairs of 4-msec noise bursts were presented to each listener with onset-to-onset
      delays ranging from 2 to 16 msec. Echo thresholds were obtained at signal
      presentation levels of 10, 20, 30, 40, and 50 dB SL. RESULTS: Results revealed
      differences between the psychometric functions of the two subject groups.
      Psychometric functions of the subjects with impaired hearing indicated higher
      echo thresholds than for the subjects with normal hearing. In addition, echo
      thresholds at 10 dB SL were significantly higher than echo thresholds measured at
      40 dB SL for both subject groups. CONCLUSION: Listeners with impaired hearing
      exhibit higher echo thresholds than listeners with normal hearing. The higher
      echo thresholds for listeners with impaired hearing may account, at least in
      part, for difficulty on tasks such as localization in everyday listening
      environments.

PMID- 12195178
TI  - ABR thresholds to tonebursts gated with Blackman and linear windows in adults
      with high-frequency sensorineural hearing loss.
AB  - OBJECTIVE: The goal of this study was to determine whether tonebursts gated on
      and off using a nonlinear, exact-Blackman-gating function would be a more
      frequency-specific stimulus for auditory brain stem response audiometry than the
      more traditional 2-1-2 cycle linearly gated toneburst. DESIGN: Toneburst ABRs
      were recorded in 10 adults with normal hearing and in 18 adults with sloping high
      frequency sensorineural hearing loss. It was hypothesized that any advantage of
      the Blackman stimuli for frequency-specific threshold assessment should be
      evident in hearing-impaired subjects with hearing loss confined to the 2000 to
      4000 Hz frequency region since spectral splatter in the toneburst stimuli could
      lead to an underestimation of hearing loss based on the ABR thresholds. ABR
      stimuli consisted of 2000- and 4000-Hz 2-1-2 (rise-plateau-fall) cycle linearly
      gated tonebursts and 1-0-1 msec exact-Blackman-gated tonebursts. An additional
      0.5-0-0.5 msec 4000-Hz Blackman-gated toneburst was used to investigate whether
      the difference in rise/fall characteristics of the linearly and Blackman-gated
      tonebursts could account for any differences in ABR results at 4000 Hz. The ABR
      toneburst stimuli were calibrated behaviorally in 15 adults with normal hearing.
      RESULTS: In the normal-hearing listeners toneburst-ABR thresholds generally
      exceeded behavioral thresholds by 10 to 13 dB for all stimuli. Correlations of
      0.85 to 0.96 were obtained between 2000 and 4000 Hz toneburst ABR thresholds and
      pure-tone audiometric thresholds in the hearing-impaired listeners. Results were
      similar for Blackman- and linearly gated stimuli. CONCLUSIONS: There were no
      clear differences between Blackman- and linearly gated tonebursts in terms of how
      well ABR thresholds predicted pure-tone thresholds at 2000 and 4000 Hz. In
      general audiometric thresholds were predicted with good accuracy (+/-15 dB) by
      the toneburst ABR thresholds. The 4000-Hz audiometric threshold was
      underestimated in one subject with a very steeply sloping hearing loss by both
      Blackman- and linearly gated toneburst ABR thresholds, indicating that
      ipsilateral masking such as notched noise would be needed to ensure frequency
      specificity in this and similar cases.

PMID- 12195179
TI  - Effects of multi-channel compression time constants on subjectively perceived
      sound quality and speech intelligibility.
AB  - OBJECTIVE: The purpose of this study was to determine the influence of the
      compression time constants in a multi-channel compression hearing aid on both
      subjectively assessed speech intelligibility and sound quality in realistic
      binaural acoustical situations for normal-hearing and hearing-impaired listeners.
      DESIGN: A nonlinear hearing aid with 15 independent compression channels of
      approximated critical bandwidth was simulated on a personal computer. Various
      everyday life situations containing different sounds such as speech and speech in
      noise were recorded binaurally through original hearing aid microphones placed in
      BTE hearing aid cases. Two experiments were run with normal hearing and hearing
      impaired subjects. For each subject, hearing thresholds were established using in
      situ audiometry. The static I/O-curve parameters in all channels of the hearing
      aid were then adjusted so that normal speech received an insertion gain
      corresponding to the NAL-R formula (Byrne & Dillon, 1986). The compression ratio
      was kept constant at 2.1:1. In the first experiment with six normal-hearing and
      six hearing-impaired subjects, the hearing aid was programmed to four different
      settings by changing only the compression time constants while all the parameters
      describing the static nonlinear Input/Output-curve were kept constant. The
      compression threshold was set to a very low value. In the second experiment with
      seven normal-hearing and eight hearing-impaired subjects, the hearing aid was
      programmed to four settings by changing the release time constants and the
      compression threshold while all other remaining parameters were kept constant.
      Using a complete A/B pair comparison procedure, subjects were presented
      binaurally with the amplified sounds and asked to subjectively assess their
      preference for each hearing aid setting with regards to speech intelligibility
      and sound quality. RESULTS AND CONCLUSIONS: In Experiment 1, all subjects showed
      a significant preference for the longest release time (4 sec) over the two
      shorter release times (400 msec and 40 msec), pertaining to quality and
      intelligibility. In combination with the long release time, the attack time (1
      msec or 100 msec) was of less importance. Larger inter-individual differences
      were observed among all subjects with regard to the perceived sound quality of
      musical and nonspeech signals. In Experiment 2 the hearing-impaired subjects
      showed a significant preference for the hearing aid setting with a long release
      time (4 sec) and a low compression threshold (20 dB SPL), both with regard to
      sound quality and speech intelligibility. With a short release time (40 msec), a
      lower compression threshold (20 dB SPL) was preferred over a higher threshold (50
      dB SPL). Among normal-hearing subjects, the same settings were also preferred for
      speech intelligibility. However, no significant differences were observed in
      these subjects regarding the assessment of sound quality. Again, more individual
      variability was found during the assessment of music and nonspeech signals. In
      sum, the preference of a rather long release time raises the question of whether
      a compression system with a very short time constant is the optimal means to
      compensate for the sensory recruitment phenomenon.

PMID- 12195181
TI  - Long-term outcomes of pelvic floor exercise and biofeedback treatment for
      patients with fecal incontinence.
AB  - PURPOSE: The aim of this study was to assess the long-term clinical and quality
      of life outcomes for patients after referral to a four-month treatment program
      for fecal incontinence based on pelvic floor exercises and biofeedback. Secondary
      objectives were to document patients' subsequent treatment activities and their
      perception of the biofeedback training; to establish the long-term outcomes and
      initial predictors for the subset of patients who did not complete the treatment,
      or who failed to improve during the program; and to correlate changes in clinical
      outcome measures and quality of life over time. METHODS: Patients were contacted
      by telephone to determine their perception of progress subsequent to the
      treatment program, any subsequent treatment or activities relating to their fecal
      incontinence, and which aspect of the treatment program they believed was most
      helpful. St. Mark's and Pescatori fecal incontinence scores were also recorded,
      along with patients' self-assessments of their incontinence severity and quality
      of life. RESULTS: Eighty-three (69 percent) patients were contacted for
      interviews at a median of 42 (range, 26-56) months after program completion. At
      the time of follow-up, patients who completed the program continued to enjoy
      strongly significant improvements in all outcome measures, with 75 percent
      perceiving a symptomatic improvement and 83 percent reporting improved quality of
      life. For many patients, improvement continued subsequent to program completion.
      Patients whose incontinence scores became worse during treatment still reported
      improvement in their quality of life and perceived incontinence severity during
      the same time period; many experienced some degree of "catch-up" in their
      continence scores during the follow-up period. Fourteen patients (17 percent)
      went on to have surgery for fecal incontinence; of these, 6 (7 percent) had a
      stoma. Twenty (24 percent) regularly took antidiarrheal medication. Thirty
      program completers (41 percent) were continuing pelvic floor exercises.
      CONCLUSIONS: This study confirms the long-term improvement in fecal incontinence
      achieved through treatment with biofeedback and pelvic floor exercises. In this
      study, patients also continued to improve after treatment completion, possibly
      because of the strong emphasis placed on patients during treatment to continue
      the pelvic floor exercises on their own. The poor correlation between quality of
      life and quantitative scores of fecal incontinence suggests that there are
      important aspects of continence that are not being appropriately recognized.

PMID- 12195182
TI  - Anal sphincter damage after vaginal delivery: relationship of anal endosonography
      and manometry to anorectal complaints.
AB  - PURPOSE: This study was designed to assess the relationship of anal
      endosonography and manometry to anorectal complaints in the evaluation of females
      a long time after vaginal delivery complicated by anal sphincter damage. METHODS:
      Thirty-four patients with anal sphincter damage after delivery, 22 with and 12
      without anorectal complaints, and 12 controls without anorectal complaints
      underwent anal endosonography, manometry, and rectal sensitivity testing.
      Complaints were assessed by questionnaire, with a median follow-up of 19 years.
      RESULTS: Median maximum anal resting pressures were significantly lower in
      patients with anal sphincter damage with complaints (31 mmHg) than in controls
      (52 mmHg; P < 0.001). Median maximum anal squeeze pressures were significantly
      lower in patients with (55 mmHg) and without (69 mmHg) complaints than in
      controls (112 mmHg; P < 0.001 for both). Maximum anal resting pressures were
      significantly lower in patients with anorectal complaints after anal sphincter
      damage than in patients without complaints (P = 0.02). Results of anal manometry
      showed a large overlap between all groups. Rectal sensitivity showed no
      significant differences between the three groups. Persisting sphincter defects,
      shown by anal endosonography, were significantly more present in patients with
      anal sphincter damage after delivery with (86 percent) and without (67 percent)
      complaints than in controls (8 percent; P < 0.001 and P < 0.01, respectively). No
      differences in the number of echocardiographically proven sphincter defects were
      found between patients with or without anorectal complaints after anal sphincter
      damage CONCLUSIONS: Echographically proven sphincter defects are strongly
      associated with a history of anal sphincter damage during delivery. Sphincter
      defects are present in the majority of patients with anorectal complaints. Anal
      manometry provides little additional therapeutic information when performed after
      anal endosonography in patients with anorectal complaints after anal sphincter
      damage during delivery.

PMID- 12195183
TI  - Long-term results and quality-of-life outcomes in patients with transsphincteric
      fistulas after muscle-filling procedure.
AB  - PURPOSE: This study was designed to evaluate long-term results and quality-of
      life outcomes after the muscle-filling procedure for posterior transsphincteric
      fistulas. METHODS: A questionnaire was mailed to 207 patients who had been
      treated by the muscle-filling procedure for posterior transsphincteric fistulas
      with cryptoglandular origin at the Social Health Insurance Hospital during a ten
      year period. One hundred fifty-one patients who returned their questionnaires
      were included in this retrospective study. Information regarding fistula
      recurrence, time required for wound healing, postoperative incontinence, overall
      satisfaction with the procedure, and quality-of-life data were surveyed from the
      returned questionnaires. RESULTS: One hundred fifty-one patients (140 males) with
      a mean age of 48 (range, 17-75) years were analyzed. The mean follow-up was 70
      (range, 12-131) months. Fistulas recurred in seven patients (4.6 percent). Fifty
      eight patients (38 percent) healed within 3 months, and 52 (34 percent) healed
      within 6 months. Eighty-four patients (56 percent) reported some reduction in
      their sense of sphincter-tightening ability after surgery. Seventy-eight patients
      (52 percent) reported some degree of incontinence. One hundred thirty-three
      patients (88 percent) were satisfied or very satisfied with their outcomes. Of
      the 18 patients (12 percent) who reported unsatisfactory or very unsatisfactory
      results, 7 experienced recurrence. Thirty-seven patients (25 percent) indicated
      one or more lifestyle alterations, including social activities (11 percent),
      travel (12 percent), sports (5 percent), diet (4 percent), housework (1 percent),
      or sexual activities (1 percent), because of incontinence after surgery. Eighteen
      patients (12 percent) had more than one restriction in their quality-of-life
      parameters. CONCLUSION: The muscle-filling procedure is a viable option in the
      treatment of transsphincteric fistulas, with a favorable recurrence rate and an
      overall patient satisfaction rate above 88 percent.

PMID- 12195184
TI  - Combined radiologic and manometric study of rectal filling sensation.
AB  - PURPOSE: Sensation is an essential aspect of fecal continence. We aimed to
      correlate manovolumetric and radiologic changes at successive levels of rectal
      filling sensation. METHODS: Combined anorectal manometry and proctography were
      performed in nine volunteers. Images, volumes, and pressures were analyzed at the
      start of the test, at 20 seconds before first sensation, and at first, constant,
      urge, and maximum tolerable sensation. RESULTS: Consecutive levels of rectal
      filling sensation were associated with progressive opening and dilation of the
      upper anal canal (up to 44 mm) and sliding down of the rectal contents (14 mm),
      which had already started before the first sensation. This coincided initially
      with a pressure decrease in the proximal anal canal (from 94 to 42 mmHg). With
      constant sensation and particularly with urge sensation, rectal pressure increase
      appeared to be responsible for further proximal anal dilation. This was
      accompanied by a significant increase of proximal anal pressure (up to 133 mmHg)
      and sharpening of the angle between the anal axis and the horizontal reference
      line. CONCLUSION: The proximal anal canal or its surrounding structures play an
      important role in the desire-to-defecate sensation. They can be activated by a
      progressive buildup of rectal reservoir pressure in the presence of a competent
      distal anal sphincter barrier.

PMID- 12195185
TI  - Cyclooxygenase-2 inhibition augments the hepatic antitumor effect of oral
      Salmonella typhimurium in a model of mouse metastatic colon cancer.
AB  - INTRODUCTION: Oral inoculation with a nontoxic, attenuated strain of Salmonella
      typhimurium reduces tumor burden and improves survival in a mouse model of
      metastatic colon cancer. These effects are likely mediated by S. typhimurium
      induced increases in hepatic natural killer leukocytes. Cyclooxygenase-2
      inhibitors may mediate antitumor effects through antiangiogenic, immune, or
      proapoptotic pathways. We hypothesized that cyclooxygenase-2 inhibitors would act
      synergistically with S. typhimurium, resulting in additional antitumor effects.
      METHODS: Four groups of mice were studied: control, S. typhimurium alone,
      cyclooxygenase-2 inhibitor alone, and S. typhimurium plus cyclooxygenase-2
      inhibitor. Mice were given normal drinking water (control, S. typhimurium alone)
      or water with 1,600 parts per million cyclooxygenase-2 inhibitor (cyclooxygenase
      2 inhibitor alone, and S. typhimurium plus cyclooxygenase-2 inhibitor) and orally
      inoculated with saline (control, cyclooxygenase-2 inhibitor alone) or 10(9) S.
      typhimurium (S. typhimurium alone, S. typhimurium plus cyclooxygenase-2
      inhibitor). Twenty-four hours later, all mice underwent laparotomy, and 5 x 10(4)
      MCA38 murine adenocarcinoma cells were injected into the spleen. On Day 14,
      hepatic tumor number and tumor volume was quantitated and hepatic leukocytes were
      analyzed by flow cytometry. RESULTS: Compared with control mice orally inoculated
      with saline, S. typhimurium-treated mice had fewer and smaller tumors; mice
      treated with cyclooxygenase-2 inhibitor alone had tumor burden similar to control
      mice, and mice treated with S. typhimurium plus cyclooxygenase-2 inhibitor had
      fewer and smaller tumors compared with all other groups. Increased liver natural
      killer cells and decreased CD4+ and CD8+ T cells were observed in both S.
      typhimurium-treated groups. No alterations in hepatic leukocyte phenotype were
      observed in mice receiving cyclooxygenase-2 inhibitor alone. CONCLUSION: Oral
      cyclooxygenase-2 inhibitor appeared to act synergistically with S. typhimurium to
      reduce tumor burden. This combination therapy may have clinical application in
      the treatment or prevention of hepatic metastases associated with colorectal
      cancer.

PMID- 12195186
TI  - Factors affecting local recurrence of colonic adenocarcinoma.
AB  - PURPOSE: The aim of this retrospective study was to determine which aspects of
      tumor morphology and histology influenced the incidence of local recurrence after
      curative resection of colonic adenocarcinoma. METHODS: Patients who had a
      curative resection for a primary colonic adenocarcinoma between 1980 and 1993
      (inclusive) were identified from the colorectal cancer database in the Department
      of Colorectal Surgery. The charts of patients diagnosed with a local recurrence
      were then reviewed and their findings at operation and histologic assessment
      analyzed. Patients were followed up for at least five years or until death.
      RESULTS: Over the period of study, 1,031 patients had a curative resection for
      colonic adenocarcinoma. Local recurrences were detected in 32 patients (3.1
      percent). The gender distribution of patients with local recurrence was 18 males
      (56.3 percent) and 14 females (43.7 percent) with a mean age of 63.4 years. The
      median time to local recurrence was 13 (range, 2-71) months. The distribution of
      primary tumors that recurred locally favored the cecum (n = 9; 28.1 percent) and
      sigmoid colon (n = 14; 43.7 percent) over other locations; these were, however,
      the most common sites of primary lesions. Less common sites included the
      ascending colon (n = 0; 0 percent), hepatic flexure (n = 2; 6.3 percent),
      transverse colon (n = 1; 3.1 percent), splenic flexure (n = 3; 9.4 percent), and
      descending colon (n = 3; 9.4 percent). Of the total number of tumors, 101 were
      found to be adherent to at least 1 other intra-abdominal viscus, and 12 (11.9
      percent) recurred locally. Other factors associated with local recurrence were
      tumor perforation and fistulation. Overall, 30 tumors (2.9 percent) were
      perforated, and 6 (20 percent) recurred locally. Four tumors (0.4 percent) were
      fistulating; of these, 2 (50 percent) recurred locally. Advanced tumor stage was
      also associated with an increased rate of local recurrence (Stage I, 0 percent;
      Stage II, 2.05 percent; Stage III, 7.0 percent; and Stage IV, 6.1 percent).
      Similarly, tumor differentiation was related to local recurrence, with no
      instances in well-differentiated tumors, 2.8 percent in moderately differentiated
      tumors, and 6.8 percent in poorly differentiated tumors. CONCLUSIONS: The
      location of the primary tumor is not a factor in producing local recurrence.
      Fixity to another viscus, perforation or fistulation, advanced stage of disease,
      and differentiation of tumor appear to increase the chances of recurrence of
      curatively resected colonic carcinoma. Although the recurrence rate is higher in
      these groups than for tumors overall, definitive oncologic surgery prevents
      recurrence in the majority of cases. No colonic tumor that was T1 or T2 (N0, N1,
      or N2) or that was well differentiated recurred locally.

PMID- 12195187
TI  - Continued rightward shift of colorectal cancer.
AB  - PURPOSE: Previous analyses of the time trends of colorectal cancer have suggested
      a shift from left-sided toward right-sided cancer sites. The aim of this study
      was to determine whether such trends in the subsite distribution of colorectal
      cancer could be confirmed in hospitalization statistics similarly as in the
      incidence data. METHODS: The inpatient files of the Department of Veterans
      Affairs and the Surveillance, Epidemiology, and End Result database of the
      National Cancer Institute were used to study the time trends of colorectal cancer
      in the United States during the past three decades. Any cancer location in the
      rectum, sigmoid, or descending colon was defined as left-sided colorectum.
      RESULTS: For the period between 1970 and 2000, the data from the Department of
      Veterans Affairs revealed a statistically significant 16 percent increase in the
      proportion of proximal lesions among white males and females, as well as a 22
      percent increase in black males. For the period between 1973 and 1997, the data
      from the Surveillance, Epidemiology, and End Result revealed a 6 percent increase
      in the proportion of proximal colon cancers among whites and blacks of both
      genders. CONCLUSIONS: The epidemiologic data confirm a rightward shift in the
      colonic distribution of cancer.

PMID- 12195188
TI  - The effects of smoking on the risk of colorectal cancer.
AB  - PURPOSE: The aim of this study was to assess the effects of smoking on the risk
      of colorectal cancer according to anatomic subsite. METHODS: Between 1979 and
      1985 a population-based case-control study of cancer at multiple sites was
      performed in Montreal, which accrued over 4,000 males in total, including cases
      of colorectal cancer, other cancers, and population controls. The present
      analysis was restricted to the 585 cases with histologically proven
      adenocarcinoma of the large bowel, aged 35 to 70 years, who underwent face-to
      face interviews and provided adequate smoking histories. Of these, 176 had cancer
      in the proximal colon, 179 had cancer in the distal colon, and 230 had rectal
      cancer. Our control group consisted of 405 cancer controls, whose tumor types
      were considered unrelated to smoking, and 500 population controls. RESULTS: We
      observed a positive association between cigar smoking and cancer of the rectum.
      We also found some suggestion of a weak positive association between cigarette
      smoking and cancer of the proximal colon, an inverse association with cancer of
      the distal colon, although neither was statistically significant, and no
      association with rectal cancer. CONCLUSIONS: Cigar smoking seems to be associated
      with the development of rectal cancer. If the positive association between
      cigarette smoking and cancer of the proximal colon is real, it might partially
      explain the proximal shift in the anatomic distribution of colorectal cancer that
      has been observed, because of the increasing prevalence of cigarette smoking
      during the middle of the 20th century.

PMID- 12195189
TI  - Quantification of histologic regression of rectal cancer after irradiation: a
      proposal for a modified staging system.
AB  - PURPOSE: Long-course preoperative radiotherapy has been recommended for rectal
      carcinoma when there is concern about the ability to perform a curative
      resection, for example, in larger tethered tumors or those sited anteriorly or
      near the anal sphincter. "Downstaging" of the tumor may occur, and this is of
      importance when estimating the prognosis and selecting postoperative therapy for
      patients. We studied the effects of preoperative chemoradiotherapy on the
      pathology of rectal cancer, and we propose a simplified measurement of tumor
      regression, the Rectal Cancer Regression Grade. METHODS: We have reviewed those
      patients who received preoperative chemoradiotherapy followed by surgical
      resection for carcinomas of the mid or distal third of the rectum found to be
      Stage T3/4 on transrectal ultrasound or CT between January 1995 and December
      1998. Patients received 45 to 50 Gy irradiation and an infusion of 5
      fluorouracil. The surgical specimens were examined by one pathologist, and the
      Rectal Cancer Regression Grade was quantified. RESULTS: Forty-two patients, mean
      age 60 (range, 42-86) years, underwent chemoradiotherapy before surgery for
      rectal carcinoma. There were 28 anterior resections (67 percent; 9 with a colonic
      pouch), 12 abdominoperineal resections (27 percent), and 2 Hartmann's procedures
      (5 percent). Comparison of preoperative and pathologic staging revealed that the
      depth of invasion was downstaged in 17 patients (38 percent), and the status of
      involved lymph nodes was downstaged in 13 (50 percent) of 26 patients. Tumor
      regression was more than 50 percent (Rectal Cancer Regression Grades 1 and 2) in
      36 patients (86 percent), with 7 patients (17 percent) having complete regression
      with absence of residual cancer cells. CONCLUSION: Significant tumor regression
      was seen in 86 percent of cases after chemoradiotherapy, with 19 patients showing
      a "good" responsiveness. We propose a modified pathologic staging system for
      irradiated rectal cancer, the Rectal Cancer Regression Grade, which includes a
      measurement of tumor regression. The utility of the proposed Rectal Cancer
      Regression Grade must be tested against long-term outcomes before its value in
      predicting prognosis and survival can be determined.

PMID- 12195190
TI  - Successful application of laparoscopic surgery to the treatment of Crohn's
      disease with fistulas.
AB  - PURPOSE: The role of laparoscopic surgery in patients with Crohn's disease
      remains to be defined, although increasingly difficult cases are being treated
      using minimally invasive techniques. We examined technical feasibility in 20
      patients with Crohn's disease associated with fistulas. METHODS: Laparoscopic
      surgery was attempted in 37 patients with stricturing ileal disease or
      ileocolonic Crohn's disease from 1994 to 2000 after failure of strict nutritional
      therapy. Twenty of these patients with a total of 31 intestinal fistulas (14
      ileoileal, 6 ileocolonic, 5 ileorectal, 2 ileovesical, 2 ileocutaneous, 1
      gastrocolic, and 1 ileoduodenal) underwent 25 operations. Fistulas were divided
      intracorporeally, except for ileoileal fistulas. Fifteen patients underwent
      ileocecal resection; six underwent strictureplasty; six underwent partial
      resection of the small intestine; three underwent segmental colonic resection;
      and one underwent resection of anastomotic recurrence. Median follow-up was 48
      (range, 5-77) months. RESULTS: Oral intake was started a median of 1 (range, 1-9)
      day after operation, and patients were discharged a median of 8 (range, 6-21)
      days after surgery. Four complications were observed in 25 operations (16
      percent), including 1 intestinal obstruction/ileus, 2 wound infections, and 1
      intra-abdominal abscess. There were no intraoperative or postoperative deaths.
      Four of the 5 operations were converted to open surgery (16 percent). Three of
      the 5 patients (60 percent) who required reoperation for anastomotic recurrence
      underwent repeated laparoscopic surgery using the same small incision.
      CONCLUSION: Laparoscopic treatment for Crohn's disease complicated by fistulas is
      feasible without high complication or conversion rates. Recurrent disease
      requiring reoperation can also be successfully treated using laparoscopic
      methods.

PMID- 12195191
TI  - Diagnostic role of anti-Saccharomyces cerevisiae mannan antibodies combined with
      antineutrophil cytoplasmic antibodies in patients with inflammatory bowel
      disease.
AB  - PURPOSE: Perinuclear antineutrophil cytoplasmic autoantibody is known to be a
      marker for ulcerative colitis, and anti-Saccharomyces cerevisiae Mannan antibody
      is a serologic marker associated with Crohn's disease. The aim of this study was
      to assess the value of detecting perinuclear antineutrophil cytoplasmic
      autoantibody and/or anti-Saccharomyces cerevisiae Mannan antibody for the
      diagnosis of ulcerative colitis, Crohn's disease, Behcet's colitis, and
      tuberculous colitis. METHODS: Serum samples were obtained from 85 patients with
      Crohn's disease, 77 with ulcerative colitis, 36 with Behcet's colitis, 14 with
      tuberculous colitis, 20 healthy controls, and 21 first-degree relatives of
      patients with Crohn's disease. Determination of perinuclear antineutrophil
      cytoplasmic autoantibody and anti-Saccharomyces cerevisiae Mannan antibody was
      performed with the standardized indirect immunofluorescence technique and an
      enzyme-linked immunosorbent assay, respectively. RESULTS: A relatively high
      percentage of patients with Crohn's disease (49.4 percent), relatives of Crohn's
      disease patients (61.9 percent), and patients with Behcet's disease (41.7
      percent) tested seropositive for anti-Saccharomyces cerevisiae Mannan antibody
      compared with normal controls (10 percent). In cases of ulcerative colitis, 44.2
      percent tested seropositive for perinuclear antineutrophil cytoplasmic
      autoantibody, whereas the controls showed 0 percent positivity. The combination
      of a positive anti-Saccharomyces cerevisiae Mannan antibody test and a negative
      perinuclear antineutrophil cytoplasmic autoantibody yielded a sensitivity and
      specificity of 48.2 and 87 percent, respectively, for Crohn's disease. The
      combination of a positive perinuclear antineutrophil cytoplasmic autoantibody
      test and a negative anti-Saccharomyces cerevisiae Mannan antibody test yielded a
      sensitivity and specificity of 36.4 and 97.6 percent, respectively, for
      ulcerative colitis. CONCLUSION: Anti-Saccharomyces cerevisiae Mannan antibody may
      be associated with Crohn's disease and Behcet's disease and perinuclear
      antineutrophil cytoplasmic autoantibody with ulcerative colitis. A combination of
      both tests may aid the differential diagnosis of inflammatory bowel disease.

PMID- 12195192
TI  - Metabolic and functional results after laparoscopic colorectal surgery: a
      randomized, controlled trial.
AB  - PURPOSE: This study was designed to compare metabolic and functional results
      after laparoscopic and open colorectal resection. METHODS: Seventy-nine patients
      were randomly assigned to laparoscopic (n = 40) or open (n = 39) colorectal
      resection. Before and after operation, the following parameters were determined:
      respiratory function (spirography and blood gas); serum level of cortisol,
      lactate, and C-reactive protein; total lymphocyte count; and CD4 and CD8
      lymphocyte subsets. Intraoperative core temperature was measured by a bladder
      probe. Postoperative pain and analgesic consumption were also monitored. RESULTS:
      Mild operative hypothermia, a trend to postoperative reduction of total
      lymphocyte count, and significant impairment of respiratory function early after
      surgery were found in both groups. Laparoscopy showed a higher CD4/CD8 ratio (P =
      0.01) on postoperative Day 1 and a faster return of C-reactive protein to
      preoperative values (P = 0.01) than in the open colorectal resection group.
      Morphine consumption in the first 48 hours after surgery was lower in the
      laparoscopic than in the open group (P = 0.02). CONCLUSIONS: Laparoscopy was
      associated with a less pronounced immunosuppression and inflammatory response and
      a lower consumption of analgesic drugs than open surgery. Moreover, our data did
      not show any additional detrimental effect of laparoscopy on either operative
      core temperature or early postoperative respiratory function.

PMID- 12195193
TI  - Pelvic exenteration and sacral resection for locally advanced primary and
      recurrent rectal cancer.
AB  - PURPOSE: The only possibility of a surgical cure in patients with locally
      advanced primary or recurrent rectal cancer would be an extended resection such
      as pelvic exenteration and sacral resection. The aim of this study was to
      evaluate the safety, tolerability, and survival benefits of these procedures.
      METHODS: Between 1988 and 1999, 64 patients with locally advanced primary or
      recurrent rectal cancer underwent abdominoperineal resection, with sacral
      resection in 9 patients, anterior pelvic exenteration in 8 patients, total pelvic
      exenteration in 27 patients, and total pelvic exenteration with sacral resection
      in 20 patients. RESULTS: Rates of morbidity, reoperation, and mortality were 50,
      4.5, and 0 percent in 22 patients with primary cancer, and 60, 2.4, and 2.4
      percent in 42 patients with recurrent disease, respectively. Major complications,
      such as sepsis, intra-abdominal abscess, and enteric fistula caused one hospital
      death and reoperation in two patients. In 21 patients who underwent curative
      resection for primary cancer, the overall five-year survival rates were 74.1
      percent for Dukes B and 47.4 percent for Dukes C, although the difference was not
      statistically significant. Thirty patients with recurrent cancer who underwent
      curative resection had significantly improved survival, with a five-year survival
      rate of 22.9 percent, compared with 12 patients who underwent palliative
      resection, resulting in a survival rate of 0 percent (P = 0.0065). CONCLUSIONS:
      Pelvic exenteration and sacral resection for primary or recurrent rectal cancer
      are tolerable procedures with a low mortality rate. Although they provide a
      survival benefit if curative resection is possible, the associated morbidity
      remains high and should be followed up closely.

PMID- 12195194
TI  - Emergent resection for acute sigmoid volvulus: results of 106 consecutive cases.
AB  - INTRODUCTION: After nonoperative decompression of acute sigmoid volvulus,
      definitive surgery is necessary because of the high risk of recurrence. However,
      the optimal surgical technique for this purpose has not been determined. METHODS:
      We studied 106 consecutive patients (mean age, 60.9 (range, 26-93) years) who
      underwent emergency resection for acute sigmoid volvulus between 1992 and 2000.
      No patient underwent preoperative decompression techniques, had the bowel
      prepared, or received on-table lavage. RESULTS: Depending on the patient's
      condition and the surgeon's preference, either primary anastomosis (57 cases) or
      Hartmann's procedure (49 cases) was performed. The overall mortality rate was 6.6
      percent (7/106). The presence of a gangrenous bowel increased the mortality rate
      to 11 percent. Wound infections were documented in 8 and 12 cases, intra
      abdominal abscess occurred in 1 and 7 cases, and subsequent surgery was required
      in 6 and 5 patients who underwent primary anastomosis and Hartmann's procedure,
      respectively. There were four cases of anastomotic dehiscence (7 percent) and two
      cases of stoma revisions (4 percent). The median length of stay was eight days
      for both those who underwent primary anastomosis (range, 3-27 days) and those who
      underwent Hartmann's procedure (range, 5-29 days). CONCLUSION: Emergent primary
      resection of the acute sigmoid volvulus with or without anastomosis is adequate
      treatment for this emergent surgical problem.

PMID- 12195195
TI  - Diltiazem heals glyceryl trinitrate-resistant chronic anal fissures: a
      prospective study.
AB  - PURPOSE: Both topical diltiazem, a calcium channel blocker, and glyceryl
      trinitrate, a nitric oxide donor, lower anal pressure and heal two-thirds of
      chronic anal fissures. This study evaluated the efficacy of diltiazem for
      fissures that failed to heal with glyceryl trinitrate. METHODS: Consecutive
      patients with persistent chronic fissures despite treatment with 0.2 percent
      glyceryl trinitrate ointment underwent anal manometry before and for 1 hour after
      application of 700 mg of 2 percent diltiazem gel to the distal anal canal.
      Patients applied diltiazem twice daily for eight weeks or until the fissure had
      healed. At fortnightly review, fissure healing was assessed, and side effects
      were noted. Patients scored symptoms of pain, bleeding, and irritation using
      linear visual analog scales at the initial and follow-up visits. RESULTS: In 39
      patients (13 males; median age, 42 (range, 20- 80) years), topical 2 percent
      diltiazem gel lowered anal resting pressure by 20 percent from a median of 93 to
      74 cm H2O (P < 0.0001, Wilcoxon), and fissures healed in 19 (49 percent) within 8
      weeks. Before diltiazem, 27 patients (69 percent) had used a complete course of
      glyceryl trinitrate (0.5 g twice daily for 8 weeks), and 12 (44 percent) of these
      healed with diltiazem. The remaining 12 patients had discontinued glyceryl
      trinitrate prematurely or used less because of headaches; 7 (58 percent) of these
      healed with diltiazem, and 5 (42 percent) did not. Side effects occurred in four
      patients (10 percent): three reported perianal itching but continued with
      treatment, and one developed headaches, drowsiness, and mood swings six weeks
      into treatment and stopped diltiazem at that time. CONCLUSION: Topical 2 percent
      diltiazem is effective treatment for glyceryl trinitrate-resistant chronic anal
      fissures. Side effects, mainly perianal itching, may occur in 10 percent of
      patients but are generally tolerated.

PMID- 12195196
TI  - Risk factors associated with posthemorrhoidectomy secondary hemorrhage: a single
      institution prospective study of 4,880 consecutive closed hemorrhoidectomies.
AB  - PURPOSE: Posthemorrhoidectomy secondary hemorrhage is a rare but serious
      complication after hemorrhoidectomy. The determination of risk factors for this
      complication may provide information to improve outcome. A prospective study was
      conducted to determine the risk factors associated with posthemorrhoidectomy
      secondary hemorrhage. METHODS: We studied 4,880 patients who underwent an
      elective closed hemorrhoidectomy by 9 proctologists in a single institution
      between January 1994 and July 1996. The variables analyzed included age, gender,
      surgeon, surgeon's seniority, suture material, aseptic preparation, and use of
      antibiotics. The logistic regression model was used to assess the independent
      association of variables with posthemorrhoidectomy secondary hemorrhage. RESULTS:
      Among the 4,880 patients, 45 (0.9 percent) developed posthemorrhoidectomy
      secondary hemorrhage. The mean interval from operation to the onset of secondary
      hemorrhage was 8.8 (range, 5-19) days. Multivariate analysis revealed that
      patient's gender and individual surgeons were both independently associated with
      risk of hemorrhage. Male patients were more likely than females to develop
      posthemorrhoidectomy secondary hemorrhage (relative risk, 2.1; 95 percent
      confidence interval, 1.1-4.1; P = 0.021). The posthemorrhoidectomy secondary
      hemorrhage rates among individual surgeons ranged from 0.2 to 2.4 percent (P =
      0.003). CONCLUSION: Our data suggest that male patients are more likely to
      develop posthemorrhoidectomy secondary hemorrhage than female patients and that
      intersurgeon variability is highly correlated with this risk.

PMID- 12195197
TI  - Prospective, randomized, controlled trial of proximally based vs. distally based
      gluteus maximus flap for anal incontinence in cadavers.
AB  - PURPOSE: The aim of this study was to compare the lengths of proximally based and
      distally based gluteus maximus flaps created as for anal sphincter reconstruction
      in soft human cadavers. METHODS: Twelve soft cadavers were used in this
      prospective, randomized, controlled study. In each cadaver, a proximally based
      flap of the gluteus maximus muscle was performed on one side and a distally based
      flap on the other. All flaps were carefully dissected with neurovascular
      preservation by one surgeon. After the dissected flap was placed across the anus,
      the length of the flap that projected beyond the anus was measured. The
      differences between such lengths of both types of flaps were assessed by paired t
      test. RESULTS: The average lengths of the parts that projected beyond the anus
      for proximally based and distally based flaps were 8.08 and 4.50 (standard
      deviation, 0.51 and 0.79) cm, respectively. The average difference was 3.58
      (standard deviation, 0.51) cm, which was statistically significant (P < 0.001).
      CONCLUSION: Results showed that proximally based flaps were significantly longer
      than distally based flaps and that transposition and wrapping around the anus
      with proximally based flaps were always easily performed without tension. These
      findings support the use of unilateral proximally based gluteus maximus flaps
      instead of unilateral or bilateral distally based flaps in patients with anal
      incontinence. The location of the neurovascular pedicle of the gluteus maximus
      was consistent at 1 cm superior and lateral to ischial tuberosity. Knowledge of
      this landmark allows quick and safe dissection of the gluteus maximus flap.

PMID- 12195198
TI  - Published evidence favors the use of suprapubic catheters in pelvic colorectal
      surgery.
AB  - INTRODUCTION: Bladder catheterization is routine during pelvic colorectal
      surgery, and transurethral catheterization is the norm. However, in gynecologic
      surgery suprapubic catheters are commonly used and are reported to be superior to
      urethral catheters. METHODS: A review of published studies comparing urethral and
      suprapubic catheters in patients undergoing colorectal surgery is presented.
      Level one evidence from randomized, controlled trials is sparse. Five randomized,
      controlled trials, most with small numbers, have been published comparing urinary
      tract infection, urinary retention, duration of catheterization, pain and
      discomfort, and patient preference. RESULTS: Urinary tract infections were
      increased in the urethral group in three of the five articles. There were no
      differences between the two techniques with respect to urinary retention, but all
      studies commented on the ease with which this complication could be assessed and
      managed in the suprapubic group. There did not seem to be any difference in
      duration of catheterization. The suprapubic group experienced less pain and
      discomfort than the urethral group, and the suprapubic catheter was preferred by
      those patients who had experienced both. CONCLUSION: The results reported favor
      suprapubic over urethral catheterization in that urinary tract infections are
      reduced, particularly in females, and the ability to attempt normal voiding is
      facilitated, particularly in males.

PMID- 12195199
TI  - Muscle tamponade to control presacral venous bleeding: report of two cases.
AB  - Massive presacral hemorrhage following rectal mobilization for benign or
      malignant conditions is an uncommon complication but one that is alarming and
      often difficult to treat. A variety of methods of hemostasis have been described,
      all with mixed degrees of success. We have used a segment of free rectus
      abdominis muscle to provide tamponade to the presacral bleeding point in two
      patients with severe bleeding. The technique was successful and may be considered
      in cases of problematic hemorrhage when other techniques have failed or
      inapplicable.

PMID- 12195200
TI  - Adenocarcinoma in the residual outflow tract after incomplete excision of a
      failed ileoanal pouch: a late complication of unrecognized Crohn's colitis:
      report of a case.
AB  - A case of adenocarcinoma complicating the outflow tract remnant of a previously
      excised ileoanal pouch is described. The pouch had failed because of unsuspected
      Crohn's disease. This is the first reported case of malignancy complicating a
      pouch that had been constructed in a patient with Crohn's disease. More
      importantly, it demonstrates that carcinoma may develop in the outflow tract
      remnant left in situ after simple pouch excision. This case suggests that
      patients who require pouch excision may benefit from excision of the outflow
      tract.

PMID- 12195201
TI  - Rectal diverticula: report of a case and review of the literature.

PMID- 12195202
TI  - Cyanoacrylate adhesive in management of severe presacral bleeding.
AB  - Effective hemostasis is critical in severe presacral hemorrhage because the
      bleeding may be fatal. We report our successful use of combined hemostatic sponge
      and cyanoacrylate glue in three patients with life-threatening presacral
      hemorrhage after abdominoperineal resection of the rectum for carcinoma.

PMID- 12195203
TI  - Total mesorectal excision is not a "new" operation.

PMID- 12195205
TI  - Anoscopy vs. retroflexion for evaluation of the anal canal.

PMID- 12195207
TI  - Mesorectal lymph nodes and their relation to the superior rectal artery: do they
      exist below or above the superior rectal artery division?

PMID- 12195209
TI  - Double flap repair of transsphincteric fistulas.

PMID- 12195216
TI  - Angioimmunoblastic T-cell lymphoma.
AB  - Angioimmunoblastic T-cell lymphoma (AIL-TCL) is a rare subtype of lymphoma,
      making up only 1% to 2% of nonHodgkin's lymphomas; however, it accounts for a
      major subset of peripheral T-cell lymphomas. Angioimmunoblastic T-cell lymphoma
      has clinical and pathologic features that set it apart from other B- and T-cell
      lymphomas. More recent studies have delineated the immunophenotypic and genetic
      features of this unusual lymphoma, and have tentatively identified the cell of
      origin of this neoplasm.

PMID- 12195217
TI  - Taking advantage of basic research: p63 is a reliable myoepithelial and stem cell
      marker.
AB  - p63 is a recently characterized p53-homolog that is consistently expressed by
      basal/somatic stem cells of stratified epithelia, myoepithelial cells of the
      breast and salivary glands, and proliferative compartment of gastric mucosa. p63
      is located on the long arm of chromosome 3 (3q27) and it encodes six isoforms,
      three transactivating (TA) and three DeltaN-isoforms. While the first three
      isoforms may act as tumor suppressor genes, the DeltaN-isoforms may inhibit the
      p53/TA-p63-driven cell cycle arrest and apoptosis. Recently, the putative
      applications of p63 in the identification of myoepithelial cells of the breast
      and basal cells of the prostate acini have been evaluated; however, no critical
      systematic analysis of its role in surgical pathology practice have hitherto been
      reported. We review the putative roles of p63 in surgical pathology practice and
      provide guidelines for future directions on p63 translational research.

PMID- 12195218
TI  - A reappraisal of "basaloid carcinoma" of the cervix, and the differential
      diagnosis of basaloid cervical neoplasms.
AB  - "Basaloid carcinoma" of the uterine cervix is a neglected and underrecognized
      entity that is not included in the current World Health Organization's
      classification of cervical neoplasms. Historically, this term has been used
      synonymously with adenoid basal carcinoma (ABC). In recent years, however, it has
      become evident that a broad spectrum of basaloid cervical neoplasms exist. At one
      end of the spectrum are low-grade lesions, such as ABC; at the opposite end of
      the spectrum there are aggressive tumors, including adenoid cystic carcinoma,
      large cell neuroendocrine carcinoma, and basaloid squamous carcinoma. The purpose
      of this review is to revisit the concept of basaloid tumors of the cervix, to
      define their morphologic spectrum, and to address potential pitfalls in the
      differential diagnosis. To avoid confusion, use of the term "basaloid squamous
      cell carcinoma" is recommended when diagnosing a cervical tumor with histologic
      features of "basaloid carcinoma," as seen in other anatomic sites. A proposed
      classification of basaloid tumors of the uterine cervix is also presented.

PMID- 12195219
TI  - Cytologic diagnosis of adenocarcinoma in biliary and pancreatic duct brushings.
AB  - Biliary and pancreatic duct brush specimens are relatively uncommon specimens
      seen by pathologists. Not only can the findings of malignancy be subtle, the
      implications of a malignant diagnosis can be significant. This review focuses on
      cholangiocarcinoma and pancreatic ductal adenocarcinoma sampled by endoscopic
      brush cytology, with an emphasis on diagnostic criteria for adenocarcinoma. In
      addition, assessment of specimen adequacy, utilization of liquid-based
      preparations, molecular diagnosis, and timing of liver transplantation in
      patients with primary sclerosing cholangitis are also briefly discussed.

PMID- 12195220
TI  - Selected case from the Arkadi m. Rywlin international pathology slide seminar:
      digital central chondrosarcoma of the hand with systemic metastases.

PMID- 12195221
TI  - Microdissection of histologic sections: past, present, and future.
AB  - Histologic and cytologic changes are central to the diagnosis and classification
      of many disease processes, particularly neoplasms. The correlation of these
      changes with genomics, proteomics, and molecular pathways entails refined
      microdissection techniques that are frequently used to procure a pure population
      of cells from complex tissue. Here we review the past, present, and future of
      some of these new advances in microdissection techniques including manual
      techniques, laser microdissection, laser capture microdissection, and laser
      catapulting.

PMID- 12195223
TI  - Editorial.

PMID- 12195224
TI  - Multifaceted purinergic regulation of stimulus-secretion coupling in the
      neurohypophysis.
AB  - The neurohypophysis is an original model of the CNS secretory system releasing
      vasopressin (AVP) and oxytocin (OXT), two neuropeptides hormones synthesized by
      the magnocellular neurons of the hypothalamus. Specific patterns of action
      potentials originating from cellular bodies of magnocellular neurons control the
      release of AVP and OT, but intra-neurohypophysis regulations do modulate the
      neuropeptides release. There is now good evidence for the effects of
      extracellular purines in the control of neurohypophysial secretion. This paper
      brings together evidence for the multiple, intricate actions of purines in the
      extracellular space of the neurohypophysis. It covers four main points. First,
      the activity-dependent release of endogenous ATP in the neurohypophysis. Second,
      the action of ATP on both neuronal and non-neuronal compartments of the neural
      lobe. Third, the termination of ATP positive feedback by ecto-nucleotidases. And
      finally the possible involvement of adenosine in the regulation of
      neurohypophysial secretion and glial plasticity. The data suggest that ATP and
      adenosine are physiological modulators of the release of neurohypophysial
      peptides by acting directly on nerve terminals and indirectly on neurohypophysial
      astrocytes. Since purinergic receptors are widespread in nervous and endocrine
      systems, the neurohypophysis appears as an useful model for studying the role of
      purines in the regulation of stimulus-secretion coupling and neuron-glia
      interactions. The feedback mechanisms found in the neurohypophysis could be
      ubiquitous, occurring throughout the central nervous system and in other
      secretory systems.

PMID- 12195225
TI  - Aspirin-sensitive asthma due to diffuse neuroendocrine system pathology.
AB  - Available clinical data on aspirin-sensitive asthma (ASA) indicate that ASA
      patients have certain disturbances in the nervous, endocrine, immune and other
      body systems. It has been found that such patients have a lower melatonin (MT)
      production in daytime, a pathology of the platelet membrane-receptor complex, and
      a pathological response to exogenic MT and acetylsalicylic acid. A hypothesis has
      been suggested in which ASA is considered as apudopathy caused by dysfunction of
      MT-producing cells. The decreased MT production and the disturbed cell
      sensitivity to MT lead to pathological changes in individual organs and
      functional systems. As a result, there is an enhanced lipid peroxidation, an
      excessive production of reactive oxygen radicals, and a reduced inhibitory action
      of MT on the 5-lipoxygenase and NO-synthase activities. The lower MT content also
      results in an intense aggregation of platelets, activating these cells and
      increasing the production of leukotrienes and nitric oxide. These changes disturb
      the pulmonary microcirculation, causing the bronchial obturation syndrome even in
      patient who do not take aspirin or other nonsteroidal anti-inflammatory drugs.
      The lower basic production of MT is also responsible for a lower content of its
      metabolite-endogenic acetylsalicylic acid, thereby increasing the sensitivity of
      melatonin-producing cells, in particular of platelets, to this acid. So, even
      minimal aspirin doses inhibit the activity of COX-1, which shunts the already
      abnormal metabolism of arachidonic acid. This, in turn, leads to a greater
      production of leukotrienes and, hence, to a severe course of the disease. This
      hypothesis has become the basis for a new pathogenetic approach to the treatment
      of ASA patients by correcting the melatonin content with peptide bioregulators-
      the epiphysis extracts--Epithalamin and Epiphamin.

PMID- 12195227
TI  - Mating types in yeast, vomeronasal organ in rodents, homosexuality in humans:
      does a guiding thread exist?
AB  - Pheromones and their receptors are the molecules used by very different organisms
      in order to join two haploid cells. It happens evidently in yeast, since the two
      blending haploid cells are also the two mating organisms, whereas in rodents
      pheromone receptors are the triggers of the vomeronasal system which, supervising
      sexual behaviors, is responsible for copulation and therefore for fertilization.
      The debate is still open about the real significance of pheromones in humans but
      a working vomeronasal organ, able to recognize pheromones of the same sex, could
      be the simplest biological explanation of homosexuality. This hypothesis is
      discussed and connected with some well known experimental data.

PMID- 12195228
TI  - Human body odour, genetic variability, and sexual orientation: a reply to D.
      Oliva.

PMID- 12195230
TI  - Preferred partner characteristics in homosexual men in relation to speculated
      patterns of brain differentiation.
AB  - OBJECTIVES: The current study was designed to test a neurohormonally based theory
      of sexual orientation and preferred partner characteristics in homosexual men.
      The theory holds that the brains of homosexual men are masculinized and feminized
      directing attraction to targets younger and more masculine than self, and the
      brains of homosexual adolescents are incompletely masculinized and feminized
      directing attraction to targets older and more masculine than self. METHODS:
      Ninety-six homosexual men completed questionnaires that asked them to rate
      morphological and behavioral characteristics associated with ethologically
      relevant indicators of masculinity. The participants made ratings for themselves
      as adolescents and adults, their current partners and idealized partners as
      adults, and their idealized partners as adolescents. RESULTS: Results of within
      subjects multivariate analyses of variance supported most of the hypotheses.
      Participants as adults rated their idealized partners as more masculine than
      themselves and their real partners on five measures: height, weight, muscle
      development, facial hair, and sexuality. As adolescents they indicated a
      preference for males older and more masculine than self. The participants in
      adulthood did not show the predicted preference for partners younger than
      themselves. CONCLUSION: The increased ratings of sexuality for self from
      adolescence to adulthood support the contention that some additional
      masculinization of the brain may occur with aging. The increased ratings of body
      size for the idealized target from adolescence to adulthood keeps the target more
      masculine then self across developmental periods. This phenomenon is consistent
      with the speculated feminization of the brain at both periods and its effects on
      partner preferences.

PMID- 12195229
TI  - Effects of putative male pheromones on female ratings of male attractiveness:
      influence of oral contraceptives and the menstrual cycle.
AB  - Previous research has revealed that natural and synthetic pheromones can enhance
      ratings of opposite sex attractiveness. The present study investigated the
      effects of exposure to male axillary secretions on female ratings of the sexual
      attractiveness of male stimuli. Thirty-two female undergraduates, half of whom
      were contraceptive pill users, rated male vignette characters and photographs of
      male faces on aspects of attractiveness. On two separate study days,
      corresponding to different phases of their menstrual cycle, stimuli were
      presented while exposed to male axillary pheromones and under a control condition
      (no pheromone). The order of testing was balanced with respect to
      pheromone/control condition and menstrual cycle phase. Pheromone exposure
      resulted in significantly higher attractiveness ratings of vignette characters
      and faces. Use of the contraceptive pill or menstrual cycle phase had equivocal
      effects on some vignette items and neither had any influence on female ratings of
      male facial attractiveness. The results of this study suggest that exposure to
      natural male axillary pheromones can significantly enhance female perceptions of
      various aspects of male attractiveness.

PMID- 12195231
TI  - Treatment of autism spectrum children with thiamine tetrahydrofurfuryl disulfide:
      a pilot study.
AB  - OBJECTIVES: In a Pilot Study, the clinical and biochemical effects of thiamine
      tetrahydrofurfuryl disulfide (TTFD) on autistic spectrum children were
      investigated. SUBJECTS AND METHODS: Ten children were studied. Diagnosis was
      confirmed through the use of form E2, a computer assessed symptom score. For
      practical reasons, TTFD was administered twice daily for two months in the form
      of rectal suppositories, each containing 50 mg of TTFD. Symptomatic responses
      were determined through the use of the computer assessed Autism Treatment
      Evaluation Checklist (ATEC) forms. The erythrocyte transketolase (TKA) and
      thiamine pyrophosphate effect (TPPE), were measured at outset and on completion
      of the study to document intracellular thiamine deficiency. Urines from patients
      were examined at outset, after 30 days and after 60 days of treatment and the
      concentrations of SH-reactive metals, total protein, sulfate, sulfite,
      thiosulfate and thiocyanate were determined. The concentrations of metals in hair
      were also determined. RESULTS: At the beginning of the study thiamine deficiency
      was observed in 3 out of the 10 patients. Out of 10 patients, 6 had initial urine
      samples containing arsenic in greater concentration than healthy controls. Traces
      of mercury were seen in urines from all of these autistic children. Following
      administration of TTFD an increase in cadmium was seen in 2 children and in lead
      in one child. Nickel was increased in the urine of one patient during treatment.
      Sulfur metabolites in urine did not differ from those measured in healthy
      children. CONCLUSIONS: Thiamine tetrahydrofurfuryl disulfide appears to have a
      beneficial clinical effect on some autistic children, since 8 of the 10 children
      improved clinically. We obtained evidence of an association of this increasingly
      occurring disease with presence of urinary SH-reactive metals, arsenic in
      particular.

PMID- 12195232
TI  - Cyproterone acetate-ethinyl estradiol treatment alters urinary 6
      sulfatoxymelatonin excretion in hyperandrogenic women.
AB  - OBJECTIVES: To investigate melatonin production in hyperandrogenic women before
      and during treatment with cyproterone acetate and ethinyl estradiol (Diane 35).
      MATERIAL AND METHODS: We studied 10 women with late onset adrenal hyperplasia due
      to 21-hydroxylase deficiency (LOCAH) and 10 women with idiopathic hirsutism (IH).
      Patients were treated with Diane 35 for four months. Fasting blood samples for
      the determination of luteinizing hormone (LH), follicle-stimulating hormone
      (FSH), testosterone and dihydroepiandrosterone sulfate (DHEAS) and 24-hour urine
      collections for the determination of 6-sulfatoxymelatonin (aMT6s) excretion were
      obtained from all patients at baseline and after 4 months of treatment. Results
      were compared with those obtained in 15 control women. RESULTS: At baseline,
      women with LOCAH had significantly higher serum testosterone, 17
      hydroxyprogesterone (17OHP) and ACTH stimulated 17OHP values than IH and control
      women. Their aMT6s values (51.0+/-20.5 mg/24h) were significantly higher than the
      values in IH (34.3+/-7.1) and control women (30.5+/-6.5) (p< 0.001). Diane 35
      treatment significantly decreased serum LH, FSH and testosterone levels and aMT6s
      values in LOCAH patients (29.8+/-16.6 mg/24h) (p<0.0001) in LOCAH patients.
      CONCLUSIONS: These results indicate that hyperandrogenic women with LOCAH have
      increased melatonin production. The normalization of aMT6s and testosterone
      values during cyproterone acetate-ethinyl estradiol treatment, suggest that sex
      steroids either directly or through the suppression of gonadotropin, modulate
      melatonin secretion in these patients.

PMID- 12195233
TI  - C-fos gene expression induced in cells in specific hypothalamic structures by
      noxious mechanical stimulation and its [correction of it's] modification by
      exposure of the skin to extremely high frequency irradiation.
AB  - OBJECTIVES: The purpose of this study was to determine: 1) The spatial pattern of
      c-fos gene expression in rat hypothalamic neurons after exposure to NMS and 2)
      The expression of c-fos gene after combined exposure to NMS and EHF irradiation
      of the rat skin. METHODS: The experiments were performed on 28 male adult Sprague
      Dawley rats. After rats were subjected to noxious mechanical stimulation (NMS) or
      its combination with EHF irradiation of the skin, cells in various hypothalamic
      structures were analyzed to determine theirs effects on c-fos gene expression, an
      accepted marker of the activation of neurons. C-Fos-like protein was revealed by
      an indirect immunoperoxidase method. RESULTS: This study revealed that NMS
      stimulates c-fos gene expression in the anterior hypothalamic nucleus (AHN),
      dorsomedial hypothalamic nucleus (DMH), ventromedial hypothalamic nucleus (VMH),
      and lateral hypothalamic area (LHA) by 157, 101, 199 and 115% respectively
      compared to control animals. Combined exposure to NMS and EHF irradiation
      directed at the skin in the region of the St36 acupuncture point projection site
      (left side) results in a decrease of the number of neurons that are activated in
      the AHN, DMH, VMH, and LHA by 33.6, 13.2, 31.0 and 32.9% respectively compared to
      the number of neurons activated by exposure to NMS by itself. EHF exposure of the
      skin of rats not subjected to NMS differentially effects the number of c-Fos
      positive cells expressed in hypothalamic structures: a decrease of 39.7% was
      observed in the number of activated neurons in the central part of LHA (level 28)
      compared to sham-irradiated animals, while an increase of 80.95% was noted in the
      number of c-Fos positive cells in the DMH compared to sham-irradiated animals.
      CONCLUSIONS: The spatial pattern and degree of activation of c-fos gene
      expression has been shown in cells of the hypothalamus of rats after exposure to
      NMS by itself and after NMS combined with EHF irradiation of the skin. The
      "stress" reaction of cells in specific hypothalamic structures has been shown to
      be decreased after EHF exposure of the skin.

PMID- 12195235
TI  - The effects of interleukin-6, leukemia inhibitory factor and interferon-gamma on
      STAT DNA binding and c-fos mRNA levels in cortical astrocytes and C6 glioma
      cells.
AB  - OBJECTIVES: The purpose of this study was to compare the effects of neurotrophic
      cytokines on the JAK/STAT transcription factors and the immediate early gene, c
      fos, in C6 glioma cells and in primary astrocyte cultures. METHODS: In this study
      we compared the effects of interleukin 6, leukemia inhibitory factor and
      interferon gamma on C6 glioma cells and on primary astrocyte cultures using
      electrophoretic mobility shift assay and quantitative solution
      hybridization/Northern Blot analysis. RESULTS: We show that interleukin 6,
      leukemia inhibitory factor and interferon gamma treatment induce the nuclear
      STAT3 and STAT1 proteins to bind to the sis inducible element of c-fos in both C6
      glioma cells and primary cortical astrocytes. Furthermore, quantitative solution
      hybridization and Northern blot analysis show the differential regulation of c
      fos mRNA levels by interleukin-6 (8.1 and 4.0 folds) and leukemia inhibitory
      factor (5.4 and 3.2 folds) in C6 and astrocyte cultures (respectively). However,
      interferon gamma increases in c-fos mRNA levels (2.9 fold in both C6 and
      astrocyte cultures) were not significant in a one way ANOVA. CONCLUSION: This
      study suggests that two initial cytokine signaling pathways are present and
      functional in C6 glioma cells and in primary astrocyte cultures.

PMID- 12195234
TI  - Dehydroepiandrosterone regulation of prolactin gene expression in the anterior
      pituitary does not depend on galanin induction.
AB  - OBJECTIVES: The effects of dehydroepiandrosterone (DHEA) on galanin (GAL) and
      prolactin (PRL) mRNA expression in the anterior pituitary of Fischer 344 rats
      were studied, taking in consideration that: (1) DHEA is an androgen with
      estrogenic activity on pituitary lactotrophs; (2) estrogens induce prolactinomas
      in Fischer 344 rats; and (3) GAL has been considered the main mediator of
      estrogen-induced lactotroph proliferation. DESIGN: Female rats were
      ovariectomized and used as controls or treated during 2 weeks with DHEA (500
      mg/kg/day or 5 mg/kg/day or 50 mg/kg/day) or estradiol (E2, 50 microg/kg/day), as
      a positive control for pituitary growth and GAL induction. GAL and PRL mRNA
      expression were studied by in situ hybridization. RESULTS: Both DHEA and E2
      induced PRL mRNA synthesis. However, DHEA neither produced pituitary enlargement
      nor GAL induction, in contrast to E2. CONCLUSIONS: Our results shows that GAL is
      not involved in the estrogenic activity of DHEA on pituitary lactotrophs, and
      suggest that DHEA effects are exerted directly on the PRL gene or through another
      mechanism(s) not related to GAL.

PMID- 12195236
TI  - Presence of isoquinoline alkaloids in molluscan ganglia.
AB  - Tetrahydropapaveroline and reticuline, isoquinoline alkaloids, were purified and
      identified in the pedal ganglia of the marine mollusk Mytilus edulis. OBJECTIVES:
      To determine the presence of tetrahydropapaveroline and reticuline, isoquinoline
      alkaloids, in animal tissues previously shown to express opiate receptors.
      METHODS AND RESULTS: This was achieved by high performance liquid chromatography
      coupled with electrochemical detection and finally identified by electro-spray
      ionization quadrupole time of flight mass spectrometry (Q-TOF). The expression of
      these two terahydroisoquinoline alkaloids in the animals neural tissue is at the
      level of 2.5+/-0.64 ng/ganglion and 1.8+/-0.52 ng/ganglion, respectively.
      CONCLUSION: This finding suggests that morphine biosynthesis may occur in Mytilus
      neural tissues, and that the biosynthesis pathway may be similar to that reported
      in the poppy plant.

PMID- 12195237
TI  - Inhibition of 2-nitropropane-induced cellular proliferation, DNA synthesis and
      histopathological changes by melatonin.
AB  - OBJECTIVES: 2-Nitropropane (2-NP) is mutagenic in a number of short-term
      mutagenicity assays in vitro and in vivo, and is a potent hepatocarcinogen in
      rats. Many studies have determined that differences in the metabolism and
      disposition of the chemicals that produce mutagenicity were not responsible for
      their observed carcinogenic differences, but that carcinogenicity correlated with
      the ability of the respective isomer to induce cell proliferation in the target
      organ. METHODS: Three groups of male rats (control, 2-NP-treated [4 mmol/kg] and
      2-NP + melatonin [10 mg/kg]) were used in the current study. Cell proliferation
      was quantitated by incorporation of 3H-thymidine, detected by autoradiography,
      into newly synthesized DNA. Histopatholgical study was carried out to investigate
      the morphological changes. RESULTS: Twenty four hours after 2-NP administration,
      there was an increase in the labelling index (LI) and grain count per labelled
      nucleus (GC/N) in the hepatocytes of 2-NP-injected rats versus those of control
      animals. The increase was 69.5% in LI and 29.4% in GC/N. Melatonin treatment, 30
      minutes preceding 2-NP, reduced the increase in LI (44.4%) and GC/N (20.7%) when
      compared with 2-NP-treated rats. Histopathology revealed multiple focal areas of
      necrosis in the liver following 2-NP injection. In the lung, there was a mucinous
      degeneration of the bronchial epithelium. Melatonin treatment restored the
      histopathological changes in both the liver and lung and they are more or less
      normal. CONCLUSION: Overall, these results seem to indicate that the stimulatory
      effect of 2-NP on the cellular proliferation and the rate of DNA synthesis in the
      liver may be one of mechanisms by which the carcinogen induces its carcinogenic
      action. Also, melatonin treatment strongly protects the studied organs against
      the toxic effect of 2-NP.

PMID- 12195239
TI  - Effect of functional pinealectomy on hippocampal lipid peroxidation, antioxidant
      enzymes and N-methyl-D-aspartate receptor subunits 2A and 2B in young and old
      rats.
AB  - OBJECTIVES: To investigate the effects of pinealectomy on lipid peroxidation,
      antioxidant status and NMDA receptor subunits 2A and 2B concentrations in
      hippocampus. DESIGN: Forty-eight male Wistar-albino rats were used. SETTINGS:
      Animals were divided into three groups: 24 h dark throughout the study (highest
      melatonin release), 24 h light exposure (light-induced functional pinealectomy)
      and 12 h light/12 h dark exposure (control group). Thereafter, each group was
      divided into two groups as young and old animals. RESULTS: There was an increase
      in NR2A and NR2B concentration in DY group compared to all other treatments. CuZn
      and Mn SOD activities were found to be increased in CO compared to CY group.
      Continual light exposure for 4 weeks did not change neural CuZn and Mn SOD
      activities. In old rats, light exposure reduced the activities of both CuZn and
      Mn SOD relative to those in the young animals. In addition, CuZn and Mn SOD
      activities were higher in dark exposed rats than in those in the continual light
      exposed or LD 12:12 rats. GSH-Px activity was found elevated in the DY rats
      compared to the CY groups. MDA levels were significantly higher in the CO than in
      the CY group. CONCLUSIONS: NR2A and NR2B receptor concentrations in hippocampus
      of the rats maintained in dark showed significant increases compared to the
      control and functional pinealectomy groups but there was no significant increase
      in lipid peroxidation.

PMID- 12195238
TI  - Neuroimmunotherapy of untreatable metastatic solid tumors with subcutaneous low
      dose interleukin-2, melatonin and naltrexone: modulation of interleukin-2-induced
      antitumor immunity by blocking the opioid system.
AB  - OBJECTIVES: The preliminary applications of the psychoneuroimmunological
      knowledges to the treatment of human diseases have confirmed the possibility to
      amplify IL-2-dependent anticancer immunity by the pineal hormone melatonin (MLT)
      or by opioid antagonist, such as naltrexone (NTX), which act by activating TH1
      lymphocytes or suppressing TH2 lymphocytes, respectively. At present, however,
      there are no data about the immunobiological effects of a concomitant
      administration of both MLT and NTX on IL-2-induced anticancer immunity. This
      preliminary study was carried out to evaluate whether the association of NTX may
      further enhance the lymphocytosis induced by the neuroimmunotherapy with IL-2
      plus MLT. MATERIALS & METHODS: The study included 14 consecutive untreatable
      metastatic solid tumor patients. According to a cross-over randomized study, the
      patients were treated during two consecutive immunotherapeutic cycles at 21-day
      intervals with IL-2 plus MLT alone or with IL-2 plus MLT plus NTX. IL-2 was
      injected subcutaneously at 3 MIU/day for 6 days/week for 4 weeks, MLT was given
      orally at 20 mg /day in the evening every day, and NTX was given orally at 100 mg
      in the morning every next day. For the immune evaluation, venous blood samples
      were drawn before the onset of treatment and at weekly intervals. RESULTS:
      Lymphocyte mean number significantly increased after both IL-2 plus MLT and IL-2
      plus MLT plus NTX. However, the concomitant administration of NTX induced a
      significantly higher increase in lymphocyte mean number with respect to that
      achieved with IL-2 plus MLT alone. In contrast, the increase in eosinophil mean
      number was significantly higher on IL-2 plus MLT alone. CONCLUSIONS: This
      preliminary study shows that the association of NTX further amplifies the
      lymphocytosis obtained by IL-2 plus MLT. Since the lymphocytosis represents the
      most important favourable prognostic variable predicting the anticancer efficacy
      of IL-2 immunotherapy, it is probable that a cancer neuroimmunotherapy with IL-2
      plus both MLT and NTX to activate TH1 and suppress TH2 cells respectively, may
      deserve more promising results in the treatment of human neoplasms according to
      the psychoneuroimnunological knowledge.

PMID- 12195240
TI  - The problem of goitre with particular consideration of goitre resulting from
      iodine deficiency (I): classification, diagnostics and treatment.
AB  - In the present review paper, the following problems have been brought up: 1)
      types of nontoxic goitre and applied classification, 2) physiological periods or
      states predisposing to non-toxic goitre development, 3) evaluation of excessive
      stimulation of the thyroid gland, 4) the treatment of iodine deficiency
      consequences (non-toxic diffuse vs. non-toxic nodular goitre), 5)
      autoimmunologically-induced non-toxic goitre, and 6) positive effects of iodine
      prophylaxis with respect to goitre prevalence. The management of non-toxic
      nodular goitre, as well as of thyroid nodules is a separate and very complex
      issue, and--at the same time--the subject of our next review paper, published in
      the same issue of NEL.

PMID- 12195241
TI  - The problem of goitre with particular consideration of goitre resulting from
      iodine deficiency (II): management of non-toxic nodular goitre and of thyroid
      nodules.
AB  - The present opinions on the therapy with L-thyroxine (L-T4) of non-toxic
      multinodular, as well as of non-toxic thyroid nodules are rather divergent. This
      treatment is based on the suppression of TSH secretion from the pituitary. There
      are no doubts that fine-needle aspiration biopsy (FNAB) performance is the first
      and--at the same time--the most significant diagnostic procedure in the case of
      thyroid structural lesions (nodules, goitre, thyroiditis). FNAB performance
      should--by all means--precede the beginning of L-T4 application for the treatment
      of non-toxic multinodular goitre or thyroid nodules. The simplicity, clearness
      and high efficacy, with comparable results in each case, are the core of good
      diagnostic algorithm. Unfortunately, not all diagnostic algorithms concerning
      thyroid nodules and multinodular goitre fulfil these important criteria.

PMID- 12195242
TI  - Pineal-regulating tetrapeptide epitalon improves eye retina condition in
      retinitis pigmentosa.
AB  - We have studied the effect of tetrapeptide Epitalon (Ala-Glu-Asp-Gly) on the
      course of congenital pigmented degeneration of the retina. The application of
      Epitalon in Campbell rats is found to intensify the bioelectric and functional
      activity of the retina due to the preservation of its morphological structure.
      Epitalon therapy in patients with degenerative retinal lesions results in a
      positive clinical effect in 90% of the cases. The analysis of Epitalon effects
      suggests that the tetrapeptide participates in the mechanisms of transcription
      common for the epiphysis and retina.

PMID- 12195243
TI  - Treatment of macular degeneration (a controlled case).
AB  - Our controlled case describes the drug possibility to stabilize the exudative
      form of Age-related Macular Degeneration. The new approach of selective
      destruction of choroidal neovascularization (CNV) can be applied in patients with
      subfoveal lesions. Photodynamic therapy (PDT) is based on the reaction of
      photoactivable drug with the light of low-energy laser beam. So far only
      verteporfin [Visudyne, Novartis] as sensitizer is marketed and laser with
      wavelength of 689 nm is used. But it is questionable whether to apply this very
      costly treatment to extremely old people. An example of treatment of 90-year old
      woman with AMD with classic form of CNV is presented. Her BCVA was 0.05 OD. She
      underwent four session of PDT. At the last visit (eighteen months after initial
      and ten months after last session of PDT) the BCVA remained 0.05 OD. The patient
      is using a special magnifying lens for reading achieving near vision of 0.32. The
      presented example indicates the necessity of detailed study of every case to
      promote the therapeutic decisions for the benefit of progress in the field.

PMID- 12195244
TI  - Results of arthroscopic subacromial decompression in patients with subacromial
      impingement and glenohumeral degenerative joint disease.
AB  - The purpose of this study was to determine the efficacy of shoulder arthroscopy
      with subacromial decompression in patients with concurrent glenohumeral
      arthrosis. A retrospective review of 36 patients who had arthroscopic subacromial
      decompression with concurrent glenohumeral degenerative joint disease was
      conducted. Office charts, operative notes, standard shoulder questionnaires,
      radiographs, and clinical examinations were used. The mean age of patients was 61
      years, with 5-year follow-up. Patients with Outerbridge grade 1, 2, or 3 changes
      on either the glenoid or humerus had a mean final L'Insalata score of 90. Ten
      patients with grade 4 changes registered an ultimate score of 50. Radiographic
      arthrosis correlated similarly but with less reliability. Arthroscopic
      subacromial decompression for resistant impingement symptoms in the face of mild
      to moderate glenohumeral degenerative joint disease can improve shoulder function
      and provide durable results. Full-thickness loss of articular cartilage or
      radiographically severe degenerative joint disease had less predictable results.

PMID- 12195245
TI  - Inferior capsular shift for multidirectional instability following failed laser
      assisted capsular shrinkage.
AB  - This report is a prospective study of 10 consecutive patients treated by open
      inferior capsular shift following failed laser-assisted capsular shrinkage. Six
      patients had true multidirectional instability, 2 had anteroinferior instability
      with multidirectional laxity, and 2 had posteroinferior instability with
      multidirectional laxity. An anterior approach was used and a humeral-side
      capsular shift performed. The mean period of follow-up was 33 months (range, 18
      47 months). On the basis of the Rowe system,9 patients had excellent results and
      1 had a poor result at final follow-up. The mean score improved from 37.5 to 94
      points on the Rowe scale, from 73 to 90.4 points on the Constant scale, and from
      1.6 to 7.7 points on a numeric satisfaction scale (P <.001 for all). The one poor
      result was in the only patient who underwent multiple attempts at open
      stabilization prior to laser-assisted capsular shrinkage. There were no
      complications. We conclude that the results of an inferior capsular shift for
      multidirectional instability are not necessarily adversely affected by a previous
      failed laser-assisted capsular shrinkage procedure.

PMID- 12195246
TI  - Static posterior subluxation of the humeral head: an unrecognized entity
      responsible for glenohumeral osteoarthritis in the young adult.
AB  - Thirteen men with a mean age of 40 years had glenohumeral arthritis and symptoms
      of stiffness, pain, and locking of the joint at presentation. Provocative test
      results for anterior or posterior instability were negative. Computed tomography
      detected posterior humeral head subluxation relative to the glenoid and posterior
      cartilage wear. All patients demonstrated this posterior subluxation in the
      absence of posterior glenoid erosion. The mean glenoid retroversion was increased
      (14.5 degrees ). Increased glenoid retroversion was observed in the contralateral
      shoulder in 4 cases, and marked static posterior subluxation was noted in the
      contralateral shoulder in 3 cases. Various surgical procedures were performed in
      5 patients to correct this arthrogenic posterior subluxation. Patients who
      underwent surgery were reviewed at a mean follow-up of 46 months with physical
      examination and computed tomography. The patients with the longer follow-up
      showed a progression of arthritis, and all cases showed persistent or recurrent
      posterior humeral subluxation. Glenohumeral arthritis with static posterior
      subluxation of the humeral head in the young adult could be the first stage of
      primary glenohumeral arthritis, predating signs of posterior glenoid erosion. Our
      attempts to correct this static posterior subluxation failed.

PMID- 12195247
TI  - Magnetic resonance imaging of painful shoulder arthroplasty.
AB  - Specialized magnetic resonance imaging (MRI) was performed in 42 painful shoulder
      arthroplasties, 22 of which underwent subsequent revision surgery, allowing
      surgical confirmation of the pathology identified on MRI. One hemiarthroplasty
      was excluded because of motion artifact, leaving 21 studies (19 patients) to be
      correlated retrospectively to the surgical findings. At the time of revision
      surgery, there were full-thickness rotator cuff tears in 11 of 21 shoulders; MRI
      correctly predicted these in 10 of 11 shoulders. Full-thickness subscapularis
      tears were the most common finding (8/11 shoulders). Of the 21 shoulders, 10 did
      not have a rotator cuff tear, and MRI correctly predicted the absence of a tear
      in 8 of 10. MRI also correctly predicted glenoid cartilage wear in 8 of 9
      shoulders. With limited pulse-sequence parameter modification, the data from this
      preliminary study suggest that MRI may be a useful technique with which to
      determine the integrity of the rotator cuff and residual cartilage and, thus, is
      potentially a tool in the management of painful shoulder arthroplasty.

PMID- 12195248
TI  - Analysis of the bicipital groove as a landmark for humeral head replacement.
AB  - Many anthropometric studies of the normal glenohumeral relationship have been
      performed in an effort to identify reference points for the correct placement of
      the humeral head prosthesis in shoulder arthroplasty. The bicipital groove offers
      a useful landmark for placement of the lateral fin of the prosthesis. However,
      when fracture surgery is performed, only the distal portion of the bicipital
      groove may be available for reference. We evaluated the course of the bicipital
      groove as it moves distally along the humerus. Computer-assisted tomography axial
      images of 21 cadaveric humeri were obtained in order to follow the course of the
      bicipital groove from proximal to distal on the humerus. With use of the bisector
      of the transepicondylar axis as a reference point, the relative change in
      position of the bicipital groove from proximal to distal was measured. The mean
      change in rotation of the lateral lip from the proximal to the distal groove was
      15.9 degrees, with an SD of 6.8 degrees (range, 4 degrees -32 degrees ). The 95%
      confidence interval range for the change was 12.8 degrees to 19 degrees. Thus, a
      significant amount of internal rotation occurs along the course of the bicipital
      groove. This has significant clinical implications when the bicipital groove is
      used as a landmark for humeral head replacement in fractures of the proximal
      humerus.

PMID- 12195249
TI  - The relative importance of acromial morphology and age with respect to rotator
      cuff pathology.
AB  - The purpose of this study was to examine the relationship between patient age,
      acromial morphology, and rotator cuff pathology. Data on 523 patients who had
      arthroscopic and/or open shoulder surgery were reviewed. Acromial morphology was
      classified by the system of Bigliani. All patients were categorized by
      postoperative diagnosis as having tendinitis of the rotator cuff, partial rotator
      cuff tear, complete rotator cuff tear, and non-rotator cuff-related pathology.
      Univariate analysis results for acromial morphology (P <.001), age (P <.001), and
      gender (P =.019) showed a significant association with rotator cuff pathology.
      Fifty percent of patients with rotator cuff tendinitis had type I acromions, and
      58% of patients with full-thickness rotator cuff tears had type III acromions.
      Stratified univariate analysis revealed no significant association between
      acromial morphology and rotator cuff pathology in patients who were over 50 years
      old. Patients with full-thickness rotator cuff tears were significantly older
      than those with partial-thickness tears or tendinitis. A larger proportion of
      male patients than female patients had full-thickness rotator cuff tears.
      Multivariable logistic regression analysis identified acromial morphology, age,
      and gender as independent multivariate predictors of rotator cuff pathology. Age,
      acromial morphology, and gender all have an independent association with rotator
      cuff pathology.

PMID- 12195250
TI  - Geometry of the proximal humerus and implications for prosthetic design.
AB  - The purpose of this study was to add critical information to the data already
      available on anthropometry of the proximal humerus. Two hundred macerated humeri
      were examined. Measurements were taken either directly on the bones or on
      standardized radiographic projections. The methodology was validated and showed a
      mean interobserver correlation of 0.94 +/- 0.067. Results were expressed in mean
      values, first SD, and minimum and maximum values, as well as the 10th and 90th
      percentiles. The frontal radius of the head ranged between 21 and 26.5 mm (10th
      respectively 90th percentile). The frontal diameter of the base of the head
      ranged between 39.4 and 50 mm. The head height ranged between 14.4 and 18.8 mm.
      The frontal radius-head height ratio ranged between 0.64 and 0.77. The
      inclination of the head ranged between 132 degrees and 142 degrees. The medial
      offset ranged between 3.9 and 8.6 mm. The posterior offset ranged between -0.4
      and 3.2 mm. The greater tuberosity offset (distance between the axis of the
      proximal humerus and the most medial insertion point of the supraspinatus tendon)
      ranged between 2.5 and 9.2 mm. Retrotorsion ranged between 7 degrees and 38.5
      degrees. The distance from the bicipital groove to the head equator ranged
      between 6 and 10.5 mm. The anatomy of the proximal humerus showed a wide range
      for variables such as the medial offset and the greater tuberosity offset but was
      surprisingly constant for the inclination and relative dimensions of the head.
      The implications for prosthetic design are as follows: stem design and insertion
      should respect the insertion facet of the supraspinatus, a constant head
      inclination is an adequate approximation, only one head height per radius is
      required, and the capability for adjustment of medial offset is mandatory.

PMID- 12195251
TI  - Shoulder instability related to epileptic seizures.
AB  - Epileptic seizures can cause shoulder dislocation and instability, but a
      characteristic pattern of instability and structural lesions is not well known.
      We reviewed 34 shoulders in 26 patients in whom the initial dislocation had been
      caused by an epileptic seizure. All patients were followed up clinically and
      radiologically for a mean of 10 years (range, 2-21 years) after initiation of
      treatment. Thirteen patients (17 shoulders) were treated for anterior
      instability. A large Hill-Sachs lesion was found 12 times and a large glenoid rim
      fracture 5 times. There were 12 recurrent and 2 locked dislocations. The
      recurrence rate after the first repair was 47% (8/17 shoulders). The final
      overall results at a mean follow-up of 10 years (range, 2-12 years) were good in
      12 cases, satisfactory in 2, and unsatisfactory in 2. The reoperation rate was
      40%. With skeletal reconstruction, 12 of 13 shoulders were stable at final follow
      up. Another 13 patients (17 shoulders) were treated for posterior dislocation. A
      large reverse Hill-Sachs lesion was observed 13 times and a posterior glenoid rim
      fracture twice. There were 15 locked but only 2 recurrent dislocations. The
      recurrence rate after repair was 12% (2/17 shoulders). The final outcome at a
      mean follow-up of 7 years (range, 2-12 years) was good in 11 shoulders and
      satisfactory in 6. The reoperation rate was 12%. Anterior and posterior
      dislocations occurred with equal frequency in this series. Large bony lesions
      were the hallmark finding in this group of patients. Skeletal reconstruction was
      necessary to obtain clinical stability, especially in the more difficult-to-treat
      anterior instability.

PMID- 12195252
TI  - Results of pectoralis major transfer with fascia lata autograft augmentation for
      scapula winging.
AB  - Fifteen patients (9 male and 6 female) with a mean age of 32.8 years (range, 17
      44 years) were examined at a mean follow-up of 64 months (range, 33-118 months)
      after undergoing pectoralis major transfer with a fascia lata autograft for
      scapular winging. Ten patients were treated as part of a worker's compensation
      claim. Twelve reported that they would undergo the procedure again. The mean Rowe
      score was 66 (range, 41-92), the mean Constant-Murley score was 74 (range, 32
      95), the mean Simple Shoulder Test score was 8 of 12 positive responses, and the
      mean American Shoulder and Elbow Surgeons score was 63 (range, 10-87). Pain
      decreased in 11 patients, whereas function improved in 10 patients. According to
      the Rowe scoring system, the results were excellent in 2 patients, good in 5,
      fair in 4, and poor in 4. Better results occur in patients attaining at least 60
      degrees of external rotation postoperatively. Although complete relief of pain
      and full function were not always achieved, most patients returned to their
      preoperative level of activity with minor adaptations.

PMID- 12195253
TI  - Cemented polyethylene versus uncemented metal-backed glenoid components in total
      shoulder arthroplasty: a prospective, double-blind, randomized study.
AB  - Thirty-nine patients (forty shoulders) with primary osteoarthritis consented to
      be randomized to receive either a cemented all-polyethylene glenoid component or
      a cementless metal-backed component at the time of total shoulder arthroplasty.
      Their mean age was 69 years. Preoperative and postoperative evaluations were
      completed at 3, 6, 12, 24, and 36 months by history, physical examination,
      radiographs, and Constant scoring system. The presence of periprosthetic
      radiolucent lines was significantly greater with polyethylene than with metal
      backed glenoids (85% vs 25%, P <.01). Of 20 radiolucent lines, 12 (60%) around
      polyethylene glenoids were present on immediate postoperative radiographs and 25%
      were progressive. No significant correlation was found between the presence of
      radiolucent lines around polyethylene glenoids and functional results (P =.3). By
      contrast, periprosthetic radiolucent lines around metal-backed glenoids were rare
      but progressive when present. The incidence of loosening of metal-backed implants
      (4 cases, 20%) was significantly higher than that observed with polyethylene
      glenoids (0%, P <.001) and was associated with component shift and severe
      osteolysis. Metal-backed glenoid loosening significantly correlated with
      deteriorating functional results and increasing pain (P <.05). Revision surgery
      was required for 4 patients in the metal-backed group (P =.02), for a
      subscapularis tear (1 case) and metal-backed glenoid component loosening (3
      cases). Computed tomography scan analysis and revision surgery revealed that
      preoperative posterior humeral subluxation may recur with time despite glenoid
      reorientation and may cause asymmetric accelerated polyethylene wear, resulting
      in metal-on-metal contact and severe osteolysis. Reimplantation of a stable
      cemented glenoid component was possible in 1 case, whereas the cavitary defect
      was packed with cancellous bone in the 2 other cases. At a minimum of 3 years'
      follow-up, the results of this study clearly show that (1) the survival rate of
      cementless, metal-backed glenoid components is inferior to cemented all
      polyethylene components and (2) the incidence of radiolucency at the glenoid
      cement interface with all-polyethylene components is high and remains a concern.
      The high rate of loosening, because of the absence of ingrowth and/or the
      accelerated polyethylene wear, has led us to abandon the use of metal-backed
      glenoids. Efforts must continue to improve glenoid component design and fixation.

PMID- 12195254
TI  - Results of elbow endoprostheses in patients with rheumatoid arthritis in
      correlation with previous operations.
AB  - Fifty-nine patients with rheumatic destruction of the elbow received 20 St Georg,
      20 GSB III, 13 Souter-Strathclyde, and 13 Kudo endoprostheses. Among the various
      prosthetic categories, 43.9% of the joints had had preceding rheumatoid surgery
      (a previous synovectomy had been performed in 10 joints at a mean of 4.1 +/- 3.7
      years and a resection interposition arthroplasty had been performed in 19 cases
      4.2 +/- 1.8 years before endoprosthetic replacement). We examined 51 patients
      with 54 prostheses after a mean follow-up of 5.7 +/- 4.1 years using the Inglis
      score and analyzing all radiographs. Complications occurred in 20% of the St
      Georg prostheses, 25% of the GSB III prostheses, and 23% of the Souter
      Strathclyde prostheses. Of the St Georg prostheses, 6 (30%) had to be exchanged,
      as well as 4 (20%) of the GSB III prostheses and 4 (30.7%) of the Souter
      Strathclyde prostheses. Of the primarily implanted joints, the St Georg
      prostheses measured 77.7 +/- 7.7 on the Inglis score, GSB III 89.6 +/- 7.2,
      Souter-Strathclyde 88.4 +/- 6.5, and Kudo 89.7 +/- 4.4. Radiolucent lines greater
      than 1 mm were observed in 26% of the St Georg prostheses, 23% of the GSB III
      prostheses, 27% of the Souter-Strathclyde prostheses, and 9% of the Kudo
      prostheses. In contrast to the clinical results, the intraoperative and
      postoperative complications, as well as the rate of failure and radiolucent
      lines, showed a statistically significant relationship to previous operations of
      the joints, especially with the resection interposition arthroplasty. We conclude
      that resection interposition arthroplasty seems to be associated with
      complications and failures when a subsequent endoprosthesis is used.

PMID- 12195255
TI  - Fragment fixation with a bone graft and dynamic staples for osteochondritis
      dissecans of the humeral capitellum.
AB  - To attain bony union of the fragment in osteochondritis dissecans of the humeral
      capitellum, fragment fixation was performed with a bone graft and dynamic staples
      in 4 patients. The staples were inserted not from the articular surface but from
      the lateral aspect of the capitellum. All patients achieved bony union without
      complication, and 3 of them returned to playing competitive baseball. At final
      follow-up after surgery (mean, 7.5 years [range, 2.1-11 years]), 3 patients were
      able to throw a ball without pain and the remaining patient felt elbow dullness
      after he played recreational-level baseball as a pitcher. These results suggest
      that the procedure of fragment fixation with a bone graft and dynamic staples can
      provide satisfactory results for osteochondritis dissecans of the humeral
      capitellum with a large osteochondral fragment.

PMID- 12195256
TI  - Comparison of survivorship between standard and long-stem souter-strathclyde
      total elbow arthroplasty.
AB  - This study compared 107 cases of rheumatoid arthritis that had the long-stem
      humeral component of the Souter-Strathclyde total elbow arthroplasty introduced
      as a primary procedure with a similar group of 202 cases that had the standard
      component. Both groups were comparable with regard to age range and sex ratio.
      Follow-up of the longer-stem component was somewhat shorter, being a mean of 4.4
      years as opposed to 9.3 years. Kaplan-Meier survival analyses were undertaken for
      both revision and radiologic loosening of components as terminal events. There
      was no significant difference between the cumulative survival of the standard and
      long-stem humeral implants when revision was the endpoint. Although survival of
      both implants was similar, the reasons for this were different. More
      specifically, for the standard humeral component, 25 out of 32 revisions were for
      humeral loosening. For the long stem, however, 5 out of a total of 7 revisions
      were due to instability; no long-stem humeral component had been revised for
      loosening. In addition, linking the components by way of a snap-fit component was
      associated with a higher rate of loosening; more specifically, 5 out of 16 cases
      were revised. As a result of this study, we recommend the use of a long-stem
      Souter-Strathclyde humeral component as a primary implant. Other crucial
      components for long-stem survival, however, are surgical technique and alignment
      of the implant.

PMID- 12195257
TI  - Comparison of tension-band and figure-of-eight wiring techniques for treatment of
      olecranon fractures.
AB  - Two different internal fixation techniques for closed displaced fractures of the
      olecranon were evaluated at a mean of 18 years after injury. Thirty-two of the
      patients received tension-band wiring, and 35 received figure-of-eight wiring.
      There were 41 women (mean age, 52 years) and 26 men (mean age, 32 years)
      included. The results revealed that 80% of the patients had no subjective
      complaints, 16% had occasional pain, and 4% had daily pain. Comparison of the
      injured and uninjured elbows demonstrated a 3 degrees reduction of flexion (P
      <.05) and a 5 degrees loss of extension (P <.01). More than 50% of the fractured
      elbows had degenerative changes (joint space narrowing, subchondral cysts,
      subchondral sclerosis, and osteophytes) (P <.001), and 4 had osteoarthritis (P
      <.05). No subjective, objective, or radiographic differences were found when the
      two techniques were compared. Removal of the hardware was performed in 81% of the
      patients with tension-band wiring and in 43% of the patients with figure-of-eight
      wiring (P <.01). The figure-of-eight technique can, therefore, be recommended, as
      it is associated with less frequent secondary procedures for hardware removal.

PMID- 12195258
TI  - Reactive bone formation after surgery for lateral epicondylitis.

PMID- 12195259
TI  - A high radial neuropathy by parosteal lipoma compression.

PMID- 12195260
TI  - Four-segment classification of proximal humeral fractures: purpose and reliable
      use.

PMID- 12195261
TI  - Introduction. Botox.

PMID- 12195262
TI  - Botulinum toxin type A: history and current cosmetic use in the upper face.
AB  - This article reviews the cosmetic use of botulinum toxin in upper face from both
      the historic and clinical viewpoints. The published literature and our current
      experience are outlined. Botulinum toxin type A in the upper face has become an
      extremely popular cosmetic procedure and is outstandingly safe.

PMID- 12195263
TI  - Botulinum toxin type A (BOTOX) for treatment of migraine.
AB  - An open-label study and 2 double-blind, placebo-controlled studies have provided
      supporting evidence of botulinum toxin type A (BTX-A) as an effective, well
      tolerated treatment for migraine. Observed durations of benefit were consistent
      with known properties of BTX-A. Findings suggest that response may vary by
      features of preinjection headaches, such as migraine frequency. The precise
      mechanism by which BTX-A provides pain relief is hypothesized to be related not
      only to acetylcholine inhibition but also to a blocking action on the
      parasympathetic nervous system. Additional studies that control factors likely to
      be related to response may lead to better understanding of the BTX-A effect on
      migraine and an optimal treatment protocol.

PMID- 12195264
TI  - Complications and adverse reactions with the use of botulinum toxin.
AB  - Botulinum toxins are the causative agents of the severe food-borne illness
      botulism. With lethal doses approximating 10(-9) g/kg body weight, these
      neurotoxins represent some of the most toxic naturally occurring substances.
      Regardless, botulinum toxin is considered a safe therapy for inappropriate muscle
      spasms with adverse effects being typically self-limited. This article deals with
      some of the complications that have occurred with these treatments. The greatest
      concern with the use of BOTOX is probably the formation of blocking antibodies
      leading to nonresponse of subsequent treatment. Prevalence of resistance is less
      than 5%. Most complications associated with its aesthetic use are few and
      anecdotal. Nevertheless, the common problems and pitfalls associated with
      aesthetic treatment of the various areas of the face and neck with botulinum
      toxin are discussed. Also included are recommendations as to how to avoid these
      very undesirable, yet common, problems.

PMID- 12195265
TI  - Other noncosmetic uses of BOTOX.
AB  - Botulinum toxin A has a wide variety of clinical applications, which are related
      by blockade of acetylcholine and often are related to abnormal muscle
      contractures. These applications include ocular disorders, disorders of the upper
      aerodigestive tract, dystonia and hemifacial spasm, cosmetic, gastrointestinal
      disorders, genitourinary disorders, management of pain, and use in autonomic
      nervous system disorders. Many of these diseases will be discussed with regard to
      their treatment with botulinum toxin compared to conventional treatments.
      Advantages and disadvantages of botulinum toxin use are delineated. General
      guidelines for adult and pediatric dosing will also be discussed.

PMID- 12195266
TI  - Botulinum toxin type B: an overview of its biochemistry and preclinical
      pharmacology.
AB  - Produced by Clostridium botulinum, botulinum toxins are high molecular weight
      protein complexes consisting of the neurotoxin and additional nontoxic proteins
      that function to protect the toxin molecule. The neurotoxin acts to inhibit the
      release of acetylcholine at the neuromuscular junction, causing muscle paralysis.
      Purified toxin complexes have found a niche in the treatment of clinical
      disorders involving muscle hyperactivity. The different serotypes are
      structurally and functionally similar; however, specific differences in neuronal
      acceptor binding sites, intracellular enzymatic sites, and species sensitivities
      suggest that each serotype is its own unique pharmacologic entity. Recently,
      botulinum toxin type B has been developed as a liquid formulation to avoid the
      lyophilization (vacuum-drying) and reconstitution processes associated with
      decreasing the potency and stability of current type A toxin preparations.
      Biochemical tests were conducted to evaluate the quality of toxin in this
      formulation. In 3 consecutive manufacturing lots, the botulinum toxin type B
      complex was found to be highly purified, intact, uniform, and consistent from lot
      to lot. Also, it showed long-term stability at refrigerator and room temperatures
      (2 to 25 degrees C). Electrophysiologic studies in cynomolgus monkeys showed that
      botulinum toxin type B is effective in paralyzing injected muscle groups, with
      minimal spread to relatively distant noninjected muscles.

PMID- 12195267
TI  - A view from the ethics committee.

PMID- 12195268
TI  - Climate change, Kyoto and the Canadian Thoracic Society.

PMID- 12195270
TI  - Characterizing and developing strategies for the treatment of community-acquired
      pneumonia at a community hospital.
AB  - BACKGROUND: Patients admitted to Lions Gate Hospital, North Vancouver, British
      Columbia, with a primary diagnosis of community-acquired pneumonia (CAP) have a
      mean length of stay (LOS) of 9.1 days compared with 7.9 days for peer group
      hospitals. This difference of 1.2 days results in an annual potential savings of
      406 bed days and warranted an investigation into the management of CAP.
      OBJECTIVE: To characterize and provide recommendations for the management of CAP.
      METHODS: A retrospective chart review of patients admitted with a primary
      diagnosis of CAP between May 1, 2000 and August 31, 2000. RESULTS: Fifty-one
      patients were included in the study, with a mean LOS of 9.9 days and a median LOS
      of five days. Based on pneumonia severity index scores calculated for each
      patient, eight patients (16%) were admitted inappropriately. Initial empirical
      antibiotic choices were consistent with the Canadian CAP guidelines in 27
      patients (53%), with inconsistencies arising mainly because cephalosporin or
      azithromycin monotherapy regimens were prescribed. Step-down from intravenous to
      oral antibiotics occurred in approximately 20 patients (39%). An additional 12
      patients (24%) could have undergone step-down, and step-down was not applicable
      in 19 patients (37%). The potential annual cost avoidance from implementing
      admission criteria based on a pneumonia severity index score, applying step-down
      criteria and promoting early discharge criteria was estimated to be $220,000.
      CONCLUSIONS: Considerable variability exists in the treatment of CAP. A CAP
      preprinted order sheet was developed to address the issues identified in the
      present study and provide consistency in the management of CAP at Lions Gate
      Hospital.

PMID- 12195271
TI  - Asthma in adolescents: a randomized, controlled trial of an asthma program for
      adolescents and young adults with severe asthma.
AB  - BACKGROUND: Asthma is common and is often poorly controlled in adolescent
      subjects. OBJECTIVE: To determine the impact of an age-specific asthma program on
      asthma control, particularly on exacerbations of asthma requiring emergency
      department treatment, and on the quality of life of adolescents with asthma.
      METHODS: The present randomized, controlled trial included patients who were 15
      to 20 years of age and had visited emergency departments for management of their
      asthma. The interventional group attended an age-specific asthma program that
      included assessment, education and management by a team of asthma educators,
      respiratory therapists and respiratory physicians. In the control group,
      spirometry was performed, and the patients continued to receive usual care from
      their regular physicians. The outcomes were assessed by a questionnaire six
      months after entry into the study. RESULTS: Ninety-three subjects entered the
      study and were randomly assigned to the intervention or control group. Of these,
      only 62 patients were available for review after six months. Subjects in both the
      control and the intervention groups showed a marked improvement in their level of
      asthma control, reflected primarily by a 73% reduction in the rate of emergency
      department attendance for asthma. Other indexes of disease control, including
      disease-specific quality of life, as assessed by questionnaires, were improved.
      There was, however, no discernible difference between the subjects in the two
      groups, with the exception of an improvement in favour of the intervention group
      in the symptom (actual difference 0.7, P=0.048) and emotional (actual difference
      0.8, P=0.028) domains of the asthma quality of life questionnaire. The overall
      quality of life score favoured the intervention group by a clinically relevant
      difference of 0.6, but this difference did not reach statistical significance
      (P=0.06). CONCLUSIONS: Although all subjects demonstrated a significant
      improvement in asthma control and quality of life, the improvement attributable
      to this intervention was limited to two domains in disease-specific quality of
      life.

PMID- 12195273
TI  - Effects of polyunsaturated fatty acids on cardiac voltage-activated K(+) currents
      in adult ferret cardiomyocytes  .
AB  - This study was carried out in adult ferret cardiomyocytes to investigate the
      effects of the n-3 polyunsaturated fatty acids (PUFAs) on voltage-gated K(+)
      currents. We report that the two outward K(+) currents: the transient outward
      K(+) current (I(to)) and the delayed rectifier K(+) current (I(K)), are both
      inhibited by the n-3 PUFAs, while the inwardly rectifying K(+) current (I(K1)) is
      unaffected by the n-3 PUFAs. Docosahexaenoic acid (C22:6n-3, DHA) produced a
      concentration dependent suppression of I(to) and I(K) in adult ferret
      cardiomyocytes with an IC(50) of 7.5 and 20 micromol/L, respectively; but not
      I(K1). In addition, eicosapentaenoic acid (C20:5n-3, EPA) had the effects on the
      three K(+) channels similar to DHA. Arachidonic acid (C20:4n-6, AA) at 5 or 10
      micromol/L, after an initial inhibitory effect on I(K), caused an activation of
      I(K),AA which was prevented by pretreatment with indomethacin, a cyclooxygenase
      inhibitor. Monounsaturated and saturated fatty acids, which are not
      antiarrhythmic, lack the effects on these K(+) currents. Our results demonstrate
      that the n-3 PUFAs inhibit cardiac I(to) and I(K) with much less potency compared
      to their effects on cardiac Na(+) and Ca(2+) currents as we reported previously.
      This inhibition of the cardiac ion currents by the n-3 PUFAs may contribute to
      their antiarrhythmic actions.

PMID- 12195272
TI  - Thunderstorm-associated asthma or shortness of breath epidemic: a Canadian case
      report.
AB  - Thunderstorm-associated asthma epidemics have been documented in the literature,
      but no Canadian experience has been reported. On July 31, 2000, a thunderstorm
      associated epidemic of asthma or shortness of breath occurred in Calgary,
      Alberta. The Calgary Health Region investigated the event using diagnostic data
      from emergency departments, an urgent care medical clinic and patient interviews,
      in addition to bioaerosol counts, pollutant data and weather data reflecting
      atmospheric conditions at that time. On July 31, 2000 and August 1, 2000, 157
      people sought care for asthma symptoms. The expected number of people to seek
      care for such symptoms in a 48 h period in Calgary is 17. Individuals with a
      personal or family history of asthma, allergies or hay fever who were not taking
      regular medication for these conditions and who were outdoors before the storm
      appeared to have been preferentially affected. A stagnant air mass the day before
      the thunderstorm may have resulted in declining bioaerosol concentrations, and
      the possible accumulation of spore and pollen reservoirs within mould and plant
      structures. The elevated bioaerosol concentrations observed on the day of the
      thunderstorm may be attributed to the sudden onset of high winds during the
      thunderstorm, which triggered a sudden release of spores and pollens into the
      atmosphere, which was probably responsible for the epidemic. Several pollutant
      levels slightly increased on the day of the storm and possibly also played a role
      in symptom development. It is unclear whether an atmospheric pressure drop
      contributed to the release of spores and pollens.

PMID- 12195274
TI  - [The sinus node itself also plays a role in heart rate slowing down during
      postnatal development].
AB  - The slowing down mechanism of heart rate during growth of the body after birth
      was studied in isolated rabbit heart and sinus node (SN) preparation with
      Langendorff perfusion method, conventional microelectrode recording and
      perforated patch for recording pacemaker current I(f). The radioimmunoassay was
      also used to measure the concentration of cAMP within SN cells. The results
      indicate that without the influence of nervous and humoral factors, the
      spontaneous heart rate would also become slower as the rabbit grew older, which
      is due to the decrease of spontaneous depolarized rate of phase 4 in SN cells.
      The negative  directed shift of the threshold potential of I(f) and the decrease
      in cAMP concentration within SN cells may be responsible for the phenomenon. The
      results obtained suggest that besides the nervous and humoral factors which
      influence the heart rate, the changes in automaticity of SN cell itself may take
      part in the slowing down process as the body grows up.

PMID- 12195275
TI  - [Okadaic acid induces the expression of glutamate transporter EAAT1 in the
      neurons of rat brain].
AB  - To study the relationship between tau hyperphosphorylation and the function of
      glutamate transporter okadaic acid (OA), a protein phosphatase inhibitor, 20 ng
      in a 0.5 microl volume, was injected into the frontal cortex of rat brain and
      immunostaining was used to observe the phosphorylation of tau protein and the
      expression of excitatory amino acid transporter 1 (EAAT1) in the brain following
      the injection. The results showed that (1) the neurons in the center of the
      injection region displayed cytoplasmic shrinkage, swelling, nuclear pyknosis, and
      dislocation at the early stage, and necrosis appeared 3 d after the injection.
      However, most neurons in the peri-injected areas showed normal morphological
      characters with immuno positive reaction for AT8, a tau phosphorylated marker;
      (2) morphological analysis showed that tau hyperphosphorylation caused by OA
      treatment was mainly observed in the axons and dendrites of neuronal cells at 6 h
      in the cell body at 1 d, which brought about dystrophic neurites and
      neurofibrillary tangle (NFT)-like pathological changes; (3) the induction of
      glutamate transporter EAAT1 was observed in the involved areas corresponding to
      that with AT8 immunopositive staining, and the number of EAAT1-positive staining
      cells markedly increased at 12 h (P<0.01), peaked at 1 d (P<0.001), then
      decreased at 3 d following the injection. Combined with a confocal laser scanning
      microscopic analysis, double fluorescent immunostaining showed that EAAT1
      positive staining appeared in neurons as well as astrocytes in the peri-injected
      areas of the frontal cortex. These results demonstrate that OA increases
      glutamate transporter EAAT1 expression in neurons while it induces tau
      hyperphosphorylation. However, the mechanism and significance of the induction of
      glutamate transporter EAAT1 expression remain to be further elucidated.

PMID- 12195276
TI  - [The expression of nestin in ischemia-injured brain of adult rat].
AB  - Immunohistochemistry and double immunofluorescent labeling techniques combined
      with confocal laser scanning microscope analysis were used to investigate the
      characteristic spatial induction profile of nestin following a transient middle
      cerebral artery occlusion in adult rat brain. The results showed that nestin was
      induced in ischemic core at 1 day after reperfusion. In addition to ischemic
      core, the expression of nestin increased in peri-ischemic I, II and III regions
      at 3 days and 1 week, then it decreased and narrowed along the rim of ischemic
      core 2 weeks after reperfusion. Double immunofluorescent labeling showed that
      nestin positive cells were mostly co-stained with GFAP,a astrocyte marker, in
      peri-ischemic I region 3 days after reperfusion. At 2 weeks, however  nestin
      cells showed a long process and the cells double stained with nestin and NSE,a
      neuonal specific marker,increased in the ischemic brain. The results suggest that
      cerebral ischemia induces nestin expression in damaged neurons  which might favor
      the neuroprotection against ischemic damage.

PMID- 12195277
TI  - [Role of nitric oxide in iron-induced toxicity in rat hearts].
AB  - The aim of the present study was to explore the effect of nitric oxide (NO) on
      iron-induced toxicity in rat hearts. Langendorff perfused rat heart and
      enzymatically isolated cardiomyocytes were used. It was shown that lipophilic Fe
      HQ reduced the contractile amplitude, velocity and end-diastolic cell length in
      the cardiomyocyte, while the left ventricular developed pressure (LVDP), +/
      dp/dt(max), heart rate and coronary flow showed biphasic alterations, which
      increased in the first 2 min and then was followed by a decline in isolated
      perfused rat heart; the contents of lactate dehydrogenase (LDH) and creatine
      kinase (CK) in the coronary effluent and the malondialdehyde (MDA) in the
      myocardium were increased. L-arginine (L-Arg), an NO precursor, reduced the
      contractile amplitude and end-diastolic cell length in the cardiomyocyte; but
      reversibly increased LVDP, +/-dp/dt(max), and coronary flow in isolated perfused
      rat heart. Pretreatment with L-Arg aggravated the Fe-HQ-induced decrease in
      contractile amplitude, velocity and end-diastolic cell length in the
      cardiomyocyte; LVDP, +/-dp/dt(max), heart rate and coronary flow were
      significantly reduced in the perfused heart, and the levels of LDH and CK
      increased in the coronary effluent. In contrast, the NOS inhibitor N(omega)-nitro
      L-arginine methyl ester (L-NAME) blocked the Fe-HQ induced change in contractile
      amplitude, velocity and end-diastolic cell length in the cardio- myocyte; it
      inhibited the decrease in LVDP, LVEDP and +/-dp/dt(max), and reduced the LDH and
      CK. Removing endothelial cells in coronary vessels attenuated the increase in
      LVDP and +/-dp/dt(max) at the beginning of Fe-HQ perfusion. It is suggested that
      L-Arg aggravates the iron-induced cardiac dysfunction, NO can mediate the iron
      induced toxicity in heart, and endothelial cells in coronary vessels play an
      important role in the early stage of the effect of iron.

PMID- 12195278
TI  - [Effect of urotensin II on the nitric oxide production in neonatal rat
      cardiomyocytes].
AB  - The aim of this study was to investigate the effect of urotensin II (U II) on the
      nitric oxide (NO) production in cultured neonatal rat cardiomyocytes. The
      endothelial nitric oxide synthase (eNOS) mRNA expression was assessed by semi
      quantitative reverse transcription-polymerase chain reaction. The activity of
      nitric oxide synthase (NOS) and NO content in cardiomyocytes were measured. The
      current results showed that U inhibited eNOS mRNA expression, the NOS activity
      and the NO production of cardiomyocytes. U II (0.1 micromol/L) inhibited the NOS
      activity and the NO production in cardiomyocytes in a time-dependent manner.
      These results suggest that the cardiovascular effect of U II might be partially
      associated with NO production in cultured neonatal rat cardiomyocytes.

PMID- 12195279
TI  - [Different effects of acetylcholine on the action potential and force contraction
      in guinea pig atrial and ventricular myocardium].
AB  - The purpose of this study was to investigate the different effects of ACh on the
      action potential and force contraction in guinea pig atrial and ventricular
      myocardium by using standard microelectrodes and force transducer. The results
      showed that the duration of the action potential (APD) of atrial myocardium was
      shortened from 208.57+/-36.05 to 101.78+/-14.41 ms (n=6, P<0.01), and the APD of
      the ventricular myocardium was shortened from 286.73+/-36.11 to 265.16+/-30.06 ms
      (n=6, P<0.01).The amplitude of the action potential (APA) of the atrial
      myocardium was decreased from 88.00+/-9.35 to 62.62+/-20.50 mV (n=6, P<0.01),
      while the APA of the ventricular myocardium did not change significantly.The
      force contraction of atrial myocardium was inhibited completely (n=6, P<0.01),
      while the force contraction of ventricular myocardium was inhibited by 37.57+/
      2.58% (n=6, P<0.01). The ACh effects correlated with its concentration. The K(D)
      of the APD shortening effects in the atrial and ventricular myocardium were 0.275
      and 0.575 micromol/L. The K(D) of the negative inotropic in the atrial and
      ventricular myocardium were 0.135 and 0.676 micromol/L, respectively. The
      corresponding data points were compared using t test between the atrial and
      ventricular myocardium, and the differences were significant when the ACh
      concentration was above 10 nmol/L. Furthermore, atropine (10 micromol/L) and CsCl
      (20 mmol/L) blocked the effects of 10 micromol/L ACh on the APD of ventricular
      myocardium, while CdCl2 (0.1 mmol/L) had no influence on these effects. In
      conclusion, ACh could shorten the action potential duration and inhibit the force
      contraction of atrial and ventricular myocardium in a concentration-dependent
      manner. There are differences in the effects of ACh on the atrial and ventricular
      myocardium. The atrial myocardium is more sensitive to ACh than the ventricular
      myocardium. It is probable that the muscarinic receptor and the potassium
      channel, but not the calcium channel, are involved in the ACh-induced shortening
      of the ventricular APD.

PMID- 12195280
TI  - [Changes in autoantibody against cardiovascular AT1-receptor during development
      of renovascular hypertension in rats].
AB  - The aim of this study was to observe the change in angiotensin II receptor
      subtype 1 (AT(1)) autoantibody during the development of renovascular
      hypertension (RVH). The Goldblatt renovascular hypertension model was established
      by the two-kidney one-clip method, and a synthetic peptide corresponding to amino
      acid sequence 165-191 of the second extracellular loop of the AT(1)-receptor was
      used as the antigen. Sera AT(1)-receptor autoantibody was detected by SA-ELISA.
      It was shown that two weeks after operation both the frequency of occurrence and
      the titre of autoantibodies to AT(1)-receptor were significantly increased as
      compared with the pre-treatment control. The increase in autoantibodies lasted
      several weeks and then decreased gradually to the pre-clipping level at 12 weeks.
      It is suggested that autoimmune mechanisms are involved in the pathogenesis of
      renovascular hypertension and the AT(1) autoantibodies may be one of the
      mechanisms leading to cardiac hypertrophy.

PMID- 12195281
TI  - [The protective effect of basic fibroblast growth factor (bFGF) and
      electroacupuncture on neurons against cerebral ischemia].
AB  - Transient cerebral ischemia/reperfusion rat model was adopted, and the method of
      HE staining, TUNEL staining (TdT-mediated dUTP Nick End Labeling) were used to
      observe the effect of electroacupuncture (EA) and basic fibroblast growth factor
      (bFGF) on neuronal death. The results evinced that the combination of EA and bFGF
      could evidently reduce the neuronal death, including both necrosis and apoptosis,
      compared with EA or bFGF application alone. It is suggested that bFGF and EA can
      complement each other and enhance the protective effect following cerebral
      ischemia.

PMID- 12195282
TI  - Thermal hyperalgesic effects induced by intracerebroventricular injection of
      interleukin-1beta in rats.
AB  - The present study was to investigate the effects of intracerebroventricular
      (i.c.v.) injection of interleukin-1beta (IL-1beta) on thermal nociception in SD
      rats. The rats were divided into control and drug-administration groups. The
      animals of control group were given vehicle solution via i.c.v. injection. The
      animals of drug-administered groups were given IL-1beta at different doses (5, 50
      and 500 pg/kg b.w.) via i.c.v. injection. IL-1 receptor antagonist (IL-1ra, 50
      ng/kg) was injected 20 min before injection of IL-1beta or vehicle solution. The
      nociceptive threshold, which was represented as paw withdrawal latency (PWL), to
      a noxious thermal stimulation was measured using an analgesiameter. I.c.v.
      injection of IL-1beta dose-dependently shortened the PWL. At the dose of 500
      pg/kg, the shortening of the PWL occurred at 20 min, reaching a peak within 40
      min, lasted 100 min after injection, then gradually returned to the baseline
      level. Pretreatment with IL-1ra completely blocked the effects of IL-1beta
      induced shortening in PWL. The results obtained suggest that IL-1beta may induce
      hyperalgesia in rats through binding to IL-1 receptors in the brain.

PMID- 12195283
TI  - [Three types of induced bursting rhythm in rat injured nerves].
AB  - Firing patterns of injured nerve fibers were recorded using the single-fiber
      firing recording technique. Under the same background firing pattern, three types
      of bursting were induced separately by EGTA, veratridine or high [Ca(2+)](o) in
      the same type of nerve fibers. The results suggest that different firing patterns
      are related to different stimuli, which means that each firing pattern carries
      corresponding neural information.

PMID- 12195284
TI  - [Effects of nitric oxide on pleural lymphatic stomata and lymphatic drainage in
      the rat].
AB  - To investigate the effects of nitric oxide (NO) on the pleural lymphatic stomata
      and lymph absorption from the pleural cavity, the NOS (nitric oxide synthase)
      inhibitor N(omega)-nitro-L-arginine-methyl-ester (L-NAME) and the NO donor
      isosorbide dinitrate (ISDN) were injected into the peritoneal cavity of the rats
      respectively. Trypan blue was used as a tracer. Then the concentrations of NO and
      trypan blue in the blood serum were measured, and the ultrastructural changes in
      pleural lymphatic stomata were observed under a scanning electron microscope
      (SEM) and studied by a computer image processing system attached to SEM. It
      turned out that the concentration of NO in the serum was 49.34+/-18.47
      micromol/L, and the area and density of the pleural lymphatic stomata were 6.80+/
      1.13 microm(2) and 170.24+/-66.60 /0.1 mm(2) respectively in the NO donor group.
      The concentration of NO reduced to 17.72+/-6.58 micromol/L, and the area and
      density of the pleural lymphatic stomata were 5.72+/-1.54 microm(2) and 61.71+/
      12.73/0.1 mm(2) in the NOS inhibitor group. We found that the area and density of
      the pleural lymphatic stomata were positively correlated with the NO quantity.
      After the tracer was injected into the pleural cavity, the NO donor group
      exhibited a higher trypan blue concentration than the control group. The ability
      of the pleura to absorb trypan blue was enhanced because of the large opening of
      the stomata. It is suggested that NO can increase lymph absorption of the pleura
      by relaxing pleural lymphatic stomata.

PMID- 12195285
TI  - [Changes in adrenomedullin and receptor activity-modifying protein 2 mRNA in
      myocardium and vessels during L-NNA-induced hypertension in rats].
AB  - To explore the changes in adrenomedullin (ADM) and receptor activity-modifying
      protein 2 (RAMP2) mRNA in myocardium and vessels in hypertension, a hypertensive
      rat model was prepared by administering L-NNA. Contents of ADM in plasma,
      myocardium and vessels were measured by radioimmunoassay (RIA). The levels of pro
      ADM mRNA of myocardium and vessels were determined by competitive quantitative RT
      PCR. The results showed that L-NNA induced hypertension and cardiomegaly. The
      ratio of heart to body weight increased by 35.5% (P<0.01). In hypertensive rats
      the ir-ADM in plasma, myocardium and vessels was increased by 80%, 72% and 57%
      (P<0.01), respectively compared with the control. The amounts of ADM mRNA in
      myocardium and vessels were increased by 50% and 109.2% (P<0.05), respectively,
      and the amounts of RAMP2 mRNA was increased by 132% and 87% (P<0.01),
      respectively, compared with control. The levels of ADM in myocardium and vessels
      were positively correlated with RAMP2 mRNA, the correlation coefficients were
      0.741 and 0.885 (P<0.01), respectively. The results obtained indicate that in
      hypertensive rats, ADM is elevated in plasma, myocardium and ves-myocardium and
      vessel, and ADM and RAMP2 mRNA are up-regulated in myocardium and vessel. The
      ADM/RAMP2 system may play an important role in the pathogenesis of hypertension.

PMID- 12195286
TI  - Effects of pregnancy cocaine exposure on the mother and fetus: a murine model.
AB  - The aim of the experiments was to develop and characterize a murine model for
      investigating the effects of prenatal cocaine exposure on the mother and fetus.
      Pregnant mice were separated into three groups: group 1 was treated with cocaine
      HCl at 10 mg/kg twice daily (COC); group 2 was treated with saline at 10 ml/kg
      twice daily (SAL); and group 3 was pair-fed with the COC dams and was injected
      with saline following the same schedule (SPF) from embryonic day (E) 8 to 17. We
      utilized high-pressure liquid chromatography (HPLC) with UV detector and
      electrochemical detector to test the concentrations of cocaine, dopamine and
      serotonin, as well as HE staining to observe morphological alterations of liver
      and placenta. Though less food intake and lower weight gain were observed in COC
      and SPF groups but not in SAL dams, lower fetal body weight and brain weight were
      only seen in COC offspring. Pharmacological analysis revealed that cocaine was
      found in fetal plasma at 15 min following intraperitoneal administration on E17,
      accompanied with elevated concentrations of dopamine (DA) and serotonin (5-HT) in
      fetal brain. We also observed morphological changes in liver and placenta of
      cocaine-exposed fetuses. The present study indicates that pregnancy cocaine
      exposure can lead to maternal undernutrition and developmental abnormality of the
      fetal brain, liver and placenta. It is suggested that the developmental
      abnormality of the fetuses induced by cocaine is due to the toxicological effect
      of cocaine but not to maternal undernutrition.

PMID- 12195287
TI  - [Role of NADH-cytochrome b(5) reductase in biosynthesis of thyroid hydrogen
      peroxide].
AB  - The activity of NADH-cytochrome b(5) reductase (b(5)R) and the levels of hydrogen
      peroxide in the thyroid of patients with Graves' disease (GD) and normal controls
      were measured with potassium ferricyanide as substrate and with the homovanillic
      acid fluorescence assay. The activity of b(5)R and the level of H2O2 in GD
      thyroid were definitely higher than those in normal control, but the activity of
      catalase in GD thyroid was not significantly different from that in normal
      thyroid. After addition of p-chloromercuribenzoate, a b(5)R inhibitor, the
      activity of b(5)R in GD and normal thyroid decreased by 85%, the level of H2O2
      decreased by 50%, and protein-bound iodine (PBI) formation by 52%. There is a
      positive correlation between the level of H2O2 and the activity of b(5)R. Our
      data indicate that b(5)R participates in thyroid hydrogen peroxide biosynthesis,
      and is an important enzyme in the production of H2O2.

PMID- 12195288
TI  - [Phytoestrogen genistein inhibits carotid sinus baroreflex in anesthetized male
      rats].
AB  - The purpose of this study was to determine the effect of phytoestrogen genistein
      (GST) on carotid sinus baroreflex in 30 anesthetized male rats by perfusing the
      isolated carotid sinus in vivo. The results obtained are as follows. (1) By
      perfusion with GST (50 micromol/L), the functional curve of baroreflex was
      shifted to the right and upward, with a peak slope (PS) decrease from 0.36+/-0.01
      to 0.23+/-0.01 (P<0.001) and a reflex decrease (RD) in mean arterial pressure
      from 39.75+/-1.58 to 27.00+/-0.60 mmHg (P<0.001), while the threshold pressure
      (TP) and saturation pressure (SP) were significantly increased from 65.63+/-2.1
      to 82.05+/-1.95 mmHg (P<0.001) and from 192.23+/-3.90 to 215.76+/-3.75 mmHg
      (P<0.001), respectively. Among the functional parameters of carotid baroreflex,
      the changes in RD, PS and TP were dose-dependent. (2) Pretreatment with Bay K
      8644 (500 nmol/L), an agonist of calcium channels, could completely abolish the
      inhibitory effect of GST on carotid baroreflex. (3) Preperfusion with an
      inhibitor of NO synthase, L-NAME (100 micromol/L), did not affect the inhibitory
      effect of GST. It is proposed that the inhibitory action of GST on carotid
      baroreflex may be mediated by the inhibition of Ca(2+) channel of vascular smooth
      muscle, but not by NO release from endothelium.

PMID- 12195289
TI  - Olfactory ensheathing glia and Schwann cells: two of a kind?
AB  - Both olfactory ensheathing cells (OECs) and Schwann cells have been shown to
      promote axonal regrowth and remyelination in the central (CNS) and peripheral
      nervous systems under experimental conditions. During development, OECs and
      Schwann cells emerge from the olfactory placode and the neural crest,
      respectively, thus sharing a common "peripheral" origin. Both cell types are
      known to express a number of different molecular markers in common, to display a
      similar morphological phenotype in culture and to respond to the same growth
      promoting molecules. Contrary to Schwann cells, OECs are found in association
      with neuronal processes in the CNS constituting the olfactory nerve layer of the
      olfactory bulb. OECs maintain their growth-promoting capacity in the CNS during
      adult life supporting the lifelong axonal growth of olfactory receptor neurons.
      Thus, OECs are considered an intermediate cell type combining a "central"
      location with "peripheral" permissiveness. Recently, the regenerative potential
      of OECs has been demonstrated in a variety of studies. However, OECs are still
      less clearly defined than Schwann cells. On designing future therapeutical
      strategies for nerve injury and disease, the important question arises as to
      whether OECs and Schwann cells are comparable cell types or whether they, indeed,
      mediate specific effects, making either the one or the other suitable for special
      applications. The present review summarizes recent data on the in vitro and in
      vivo properties of OECs and critically compares the analogies and differences in
      the biology of both cell types relevant in the above-mentioned context.

PMID- 12195290
TI  - Ruminal muscle of sheep is innervated by non-polarized pathways of cholinergic
      and nitrergic myenteric neurones.
AB  - The motility patterns of the reticulorumen evoke mainly mixing of the ingesta. So
      far unknown, intrinsic neural circuits of the enteric nervous system are involved
      in the control of these motility patterns. The aim of the study was to
      characterize neurochemically sheep ruminal myenteric neurones, in particular the
      neural pathways innervating the ruminal muscle layers. Cell bodies within the
      myenteric plexus projecting to the longitudinal or circular muscle layer were
      retrogradely labelled by direct application of the fluorescent tracer 1,1'
      didodecyl-3,3,3',3'-tetramethyl indocarbocyanine perchlorate (DiI) onto the
      circular or longitudinal muscle. The neurochemical code of myenteric neurones was
      identified by their immunoreactivity for choline acetyltransferase (ChAT), nitric
      oxide synthase (NOS), substance P (SP) and vasoactive intestinal peptide (VIP).
      According to their neurochemical code, ruminal myenteric neurones were divided
      into three populations: ChAT/SP (68% of all myenteric neurones), NOS/VIP (26% of
      all myenteric neurones) and ChAT/- (5% of all myenteric neurones). Application of
      DiI onto the circular or longitudinal muscle revealed on average 64 or 44
      labelled cell bodies in the myenteric plexus, respectively. DiI-labelled neurones
      expressed the code ChAT/SP or NOS/VIP. In the pathways to circular or
      longitudinal muscle, ChAT/SP-positive neurones outnumbered NOS/VIP-immunoreactive
      neurones by 5:1 and 2:1. Pathways to the circular or longitudinal muscle did not
      exhibit any pronounced polarized innervation patterns. This study demonstrated
      specific projections of myenteric neurones to the ruminal muscle. Neurones
      expressing the code ChAT/SP might function as excitatory muscle motor neurones,
      whereas NOS/VIP neurones are likely to act as inhibitory muscle motor neurones.

PMID- 12195291
TI  - Calbindin and calretinin immunoreactivities in the retina of a chondrostean,
      Acipenser baeri.
AB  - The distribution of calbindin and calretinin in the retina of the sturgeon
      Acipenser baeri was studied with immunocytochemistry. Western blot analysis of
      brain extracts, together with immunocytochemical results in the retina and brain,
      indicated the presence of the two calcium-binding proteins in sturgeon. Calbindin
      immunocytochemistry revealed only a large displaced bipolar cell type with
      narrowly stratified axons, similar to some mixed rod and cones bipolar cells
      described in teleosts. The plexus formed by the axons of these cells in the inner
      plexiform sublayer was similar to that formed by calbindin-immunoreactive diffuse
      bipolar cells of some mammals. Calretinin immunocytochemistry also stained these
      displaced bipolar cells, most ganglion cells including displaced ganglion cells
      (Dogiel cells), and some amacrine cells of the inner nuclear layer. The
      distribution of calbindin and calretinin immunoreactivities in the retina of a
      primitive bony fish indicates that these proteins are highly specific to the cell
      type.

PMID- 12195292
TI  - Comparative immunohistochemical study of normal, hyperplastic and neoplastic C
      cells of the rat thyroid gland.
AB  - In rats, the frequency of spontaneous C-cell tumours is very high and is both age
      and gender dependent. The three specific stages of neoplastic progression can be
      distinguished into diffuse C-cell hyperplasia, focal C-cell hyperplasia and bona
      fide C-cell tumours. Based on this hypothetical model of human medullary thyroid
      carcinoma (MTC), we carried out an immunohistochemical study using different
      markers (calcitonin, calcitonin gene-related peptide, somatostatin and
      chromogranin) to verify the existence of any relationship between their
      expression and the successive steps of tumour development. We found a
      characteristic immunohistochemical staining pattern, particularly for calcitonin
      and somatostatin, which distinguishes C-cell tumours from both normal and
      hyperplastic C cells, with no differences related to the gender of the animals
      under study. Specifically, a considerable heterogeneity in calcitonin expression
      was only displayed by C-cell carcinomas, being less pronounced in C-cell
      adenomas. As for somatostatin, this regulatory peptide was found only in a
      minority of calcitonin-positive cells in normal and hyperplastic glands. However,
      in some C-cell adenomas and most C-cell carcinomas nearly all calcitonin-positive
      cells also coexpressed somatostatin. We conclude that rat C-cell neoplasms
      constitute a very particular tumour entity which shares many but not all
      immunohistochemical features with human MTC.

PMID- 12195294
TI  - Endothelin-B (ET(B)) receptor distribution in tissues of the lizard Podarcis
      sicula.
AB  - Although the structural and pharmacological properties of endothelin (ET)
      receptors have been studied, little is known concerning their physiological
      significance, even if each subtype is supposed to have a distinct physiological
      action. Thus, to further elucidate the physiological function of this receptor,
      we examined the presence and distribution of the endothelin-B receptor (ET(B))
      subtype in tissues of the lizard Podarcis sicula, using immunoblotting and
      immunohistochemistry. Immunoblotting indicated that, although the ET(B) receptor
      appears to be ubiquitous, it is present at different levels in the tissues
      examined. Furthermore, immunohistochemistry showed that this receptor is very
      abundant in endothelial cells of all tissues, suggesting that there is an ET(B)
      mediated autocrine system of endothelin, which plays an important role in the
      regulation of endothelial cell function. On the other hand, the presence of ET(B)
      immunoreactivity also in endocrine systems such as adrenal and thyroid glands
      suggests an involvement also in the paracrine system of these organs.

PMID- 12195293
TI  - The unique ultrastructure of secretory membranes in gastric parietal cells
      depends upon the presence of H+, K+ -ATPase.
AB  - Ion transporters play a central role in gastric acid secretion. To determine
      whether some of these transporters are necessary for the normal ultrastructure of
      secretory membranes in gastric parietal cells, mice lacking transporters for H+,
      K+, Cl-, and Na+ were examined for alterations in volume density (Vd) of
      basolateral, apical, tubulovesicular and canalicular membranes, microvillar
      dimensions, membrane flexibility, and ultrastructure. In mice lacking Na+/H+
      exchanger 1 (NHE1) or the Na+-K+-2Cl- cotransporter (NKCC1), the ultrastructure
      and Vd of secretory membranes and the secretory canalicular to tubulovesicular
      membrane ratio (SC/TV), a morphological correlate of secretory activity, were
      similar to those of wild-type mice. In mice lacking Na+/H+ exchanger 2 (NHE2) or
      gastric H+, K+ -ATPase alpha- or beta-subunits, the SC/TV ratio and Vd of
      secretory membranes were decreased, though canaliculi were often dilated. In H+,
      K+ -ATPase-deficient parietal cells, canalicular folds were decreased, normally
      abundant tubulovesicles were replaced with a few rigid round vesicles, and
      microvilli were sparse, stiff and short, in contrast to the long and flexible
      microvilli in wild-type cells. In addition, microvilli of the H+, K+ -ATPase
      deficient parietal cells had centrally bundled F-actin filaments, unlike the
      microvilli of wild-type cells, in which actin filaments were peripherally
      positioned concentric to the plasmalemma. Data showed that the absence of H+, K+ 
      ATPase produced fundamental changes in parietal cell membrane ultrastructure,
      suggesting that the pump provides an essential link between the membranes and F
      actin, critical to the gross architecture and suppleness of the secretory
      membranes.

PMID- 12195295
TI  - Quantitative measurement of the splice variants 120 and 164 of the angiogenic
      peptide vascular endothelial growth factor in the time flow of fracture healing:
      a study in the rat.
AB  - Formation of new blood vessels is essential for the process of wound and fracture
      healing. Little is known about the time-dependent expression and the involved
      splice variants of the vascular endothelial growth factor (VEGF). We therefore
      quantified and differentiated the angiogenic factor VEGF and its receptors
      (VEGFR) in a rat fracture model by immunohistochemical, biochemical and molecular
      biological methods. VEGF could be immunostained in chondrocytes and osteoblasts
      of the callus, but not in fibrous callus. In the capillaries, VEGFR-1 (flt-1) and
      VEGFR-2 (flk-1/KDR) were also visualized. Both receptors were also detectable in
      some chondrocytes and in osteoclasts. Enzyme-linked immunosorbent assay (ELISA)
      measurements showed high levels of VEGF in fractured tibiae and negligible ones
      in non-injured bone. Reverse transcriptase-polymerase chain reaction (RT-PCR)
      revealed expression of the rat splice variants VEGF(120) and VEGF(164) during the
      course of fracture healing, which corresponds to human VEGF121 and VEGF165 splice
      variants. VEGF plays the most important role during the early phase of fracture
      healing, but VEGF concentrations decrease further after day 5.

PMID- 12195296
TI  - Massive apoptosis of colonocytes induced by butyrate deprivation overloads
      resident macrophages and promotes the recruitment of circulating monocytes.
AB  - Our previous investigations demonstrated a rapid, massive apoptosis of
      colonocytes after butyrate deprivation. However, while in vitro apoptotic bodies
      and cells were sludged at the epithelial surface, in vivo they were phagocytosed
      by the resident macrophages. In the present study the guinea pig colon was
      perfused in vivo in the presence or absence of butyrate with the aim of
      identifying the cells involved in the removal of apoptotic material and the
      method of clearance. Morphological, immunohistochemical and DNA fragmentation
      analyses were applied. The results demonstrated massive apoptosis of colonocytes
      in the absence of butyrate. The resident macrophages were tightly clustered below
      the surface epithelium. Aided by cytoplasmatic projections they phagocytosed and
      transported apoptotic material from the epithelial intercellular spaces into
      their bodies. Apparently, the macrophages could not cope with the great amount of
      apoptotic material they had to eliminate: the recruitment of circulating
      monocytes occurred. This was revealed by the application of antibodies directed
      against MAC 387, CD68 (PG-M1), and S-100, which detected distinct
      monocyte/macrophage populations in the lamina propria. The recruited cells were
      phenotypically different from resident macrophages, their occurrence being
      typical in inflamed tissues. In conclusion, butyrate deprivation in vivo led to
      untimely death of colonocytes and triggered changes in the lamina propria
      indicative of an inflammatory response.

PMID- 12195297
TI  - Cellular autophagic capacity changes during azaserine-induced tumour progression
      in the rat pancreas. Up-regulation in all premalignant stages and down-regulation
      with loss of cycloheximide sensitivity of segregation along with malignant
      transformation.
AB  - The knowledge of alterations in regulation of autophagy during tumorigenesis may
      also help our understanding of its normal control. We established an experimental
      system and reported recently that autophagic capacity, measured as the cell's
      capability of increasing segregation (formation of autophagosomes) and subsequent
      degradation of cytoplasmic quanta were highly increased in premalignant nodule
      cells 6 months after initiation by azaserine in the rat pancreas in vivo. In the
      present study, we followed changes of these autophagic functions throughout the
      tumour progression. We carried out electron-microscopic morphometrical analysis
      of the expansion of autophagic vacuole compartment and subcompartments induced by
      vinblastine (an in vivo segregation enhancer), as well as their regression upon
      segregation-inhibitor cycloheximide post-treatment. Premalignant tumour samples
      were taken at month 5, month 8 (nodules), month 10 and month 15 (adenomas) after
      initiation. In all these stages, a highly increased and varying autophagic
      capacity was found compared with the host tissue. The basal (non-stimulated)
      autophagic compartment was measurable only at month 5 and month 15, and its
      regression upon cycloheximide was consistent with increased basal autophagic
      activity. Compared with the host tissue, autophagic capacity profoundly decreased
      in the differentiated and anaplastic adenocarcinomas at month 20, when,
      surprisingly, cycloheximide was unable to inhibit segregation. Our conclusion is
      that down-regulation of the cycloheximide sensitive segregation and a partly
      compensatory up-regulation of an alternative pathway of segregation might occur
      along with malignant transformation.

PMID- 12195298
TI  - Signal transduction and regulation of melatonin synthesis in bovine pinealocytes:
      impact of adrenergic, peptidergic and cholinergic stimuli.
AB  - Limited studies of the regulation of pineal melatonin biosynthesis in ungulates
      indicate that it differs considerably from that in rodents. Here we have
      investigated several signal transduction cascades and their impact on melatonin
      synthesis in bovine pinealocytes. Norepinephrine increased the intracellular
      calcium ion concentration ([Ca2+]i) via alpha(1)-adrenergic receptors. Activation
      of beta-adrenergic receptors enhanced cAMP accumulation and rapidly elevated
      arylalkylamine N-acetyltransferase (AANAT) activity and melatonin secretion. The
      beta-adrenergically evoked increases in AANAT activity were potentiated by
      alpha(1)-adrenergic stimulation, but this was not seen with cAMP or melatonin
      production. PACAP treatment caused small increases in cAMP, AANAT activity and
      melatonin biosynthesis, apparently in a subpopulation of cells. VIP and glutamate
      did not influence any of these parameters. Activation of nicotinic and muscarinic
      acetylcholine receptors increased [Ca2+]i, but did not alter cAMP levels, AANAT
      activity or melatonin production. Our study reveals that discrete differences in
      pineal signal transduction exist between the cow and rodent, and emphasizes the
      potential importance that the analysis of ungulate pinealocytes may play in
      understanding regulation of pineal melatonin biosynthesis in primates and man,
      whose melatonin-generating system appears to be more similar to that in ungulates
      than to that in rodents.

PMID- 12195299
TI  - Pseudophosphorylated prolactin (S179D PRL) inhibits growth and promotes beta
      casein gene expression in the rat mammary gland.
AB  - We have investigated the individual roles of unmodified prolactin (U-PRL) and a
      mimic of phosphorylated PRL (S179D PRL) in mammary development. Recombinant
      versions of the PRLs were delivered to rats throughout pregnancy at a rate of 6
      microg/24 h per rat and to non-pregnant females at a rate of 24 microg/24 h per
      rat. Measurement of progesterone, corticosterone, and estradiol showed no effect
      of the administered PRLs on the levels of these other mammotropic hormones.
      Histological and morphometric analysis showed U-PRL to cause mammary growth,
      whereas S179D PRL inhibited growth. Molecular analysis demonstrated decreased
      beta-casein expression in the mammary glands of the U-PRL-treated animals at term
      and increased beta-casein expression in the mammary glands of the S179D PRL
      treated animals. Superior beta-casein gene expression in response to S179D PRL
      versus U-PRL was confirmed in HC11 cells. We conclude that U-PRL is important for
      growth, whereas S179D PRL promotes at least one measure of differentiated
      function in the mammary gland.

PMID- 12195300
TI  - Cervical spine in patients with diastrophic dysplasia--radiographic findings in
      122 patients.
AB  - BACKGROUND: In previous studies, typical radiological findings in the cervical
      spine of patients with diastrophic dysplasia (DD) have been kyphosis,
      displacement of the vertebrae, spina bifida occulta (SBO), anterior hypoplasia of
      vertebrae C3-5, and hyperplasia and dysmorphism of the odontoid process.
      OBJECTIVES: To make a radiological analysis of the cervical spine in patients
      with DD. MATERIALS AND METHODS: The study comprised 122 patients (50 males, 72
      females), with an average age of 19 years (range newborn-63 years). Follow-up was
      available on 62 patients (51%), for an average duration of 11 years. Cervical
      spine alignment was measured according to Cobb's method. The height (H) and depth
      (D) of the vertebral body and sagittal diameter (S) of the spinal canal were
      measured. H/D and S/D ratios were then calculated from the measurements. The
      shape of the vertebrae was assessed. Displacement and movement of cervical
      vertebrae in neutral and bending radiographs were measured. RESULTS. The average
      lordosis in the last radiograph was 17(degrees) (range 4 degrees -55(degrees)).
      Five (4%) patients had a cervical kyphosis with an average of 92(degrees) (range
      10-165(degrees)) on their last radiograph. The H/D ratio increased slowly during
      growth and showed significant correlation with age. There was no growth spurt at
      puberty. The S/D ratio was fairly stable until 7-8 years of age, when it started
      to decline slowly. The percentage of vertebrae with a flat vertebral body and
      narrow spinal canal value tended to increase with age. Vertebral hypoplasia and
      displacement between vertebrae were most common in the mid-cervical region and
      resolved spontaneously with age. Degenerative changes seemed to increase with age
      and were already visible during the second decade of life. SBO was noted in 79%
      of patients. CONCLUSIONS: The most common alignment in the cervical spine is
      lordosis in adulthood. The vertebral bodies are flattened and the spinal canal is
      narrowed. Vertebral body hypoplasia and displacement usually resolve
      spontaneously during growth. Degenerative changes in the cervical spine are
      common, but vertebral anomalies are rare. Prevalence of SBO is high.

PMID- 12195301
TI  - Gracile bone dysplasias.
AB  - Gracile bone dysplasias constitute a group of disorders characterised by
      extremely slender bones with or without fractures. We report four newborns, two
      of whom showed multiple fractures. Two babies had osteocraniostenosis and one had
      features of oligohydramnios sequence. The diagnosis in the fourth newborn, which
      showed thin long bones and clavicles and extremely thin, poorly ossified ribs, is
      uncertain. Exact diagnosis of a gracile bone dysplasia is important for genetic
      counselling and medico-legal reasons.

PMID- 12195302
TI  - Cephalometrics in children with Down's syndrome.
AB  - AIMS: To describe the craniofacial morphology of a group of patients with Down's
      syndrome using a cephalometric analysis of the lateral skull radiograph.
      MATERIALS AND METHODS: The studied sample consisted of 39 patients with Down's
      syndrome (24 boys, 15 girls) ranging from 7 to 18 years of age. The computerized
      cephalometric study of the lateral skull radiograph of each patient was carried
      out using the method described by Ricketts. RESULTS: Anterior cross-bite was
      observed in 38.4% of patients and diminished interincisal angle in 77%. Skeletal
      parameters matched the clinical norm, indicating mesofacial biotype, i.e., normal
      maxillomandibular growth. The lower incisors protruded in 84.6% of the
      individuals studied and were proinclined in 77%; upper incisors were protruded in
      77% of the sample. The lower lip protruded in 84.6%. Analysis of craniofacial
      parameters showed average values within the clinical norm. Analysis of the inner
      cranium demonstrated normal inclination of the cranial base, while the length of
      the anterior skull base was diminished in 53.8%. CONCLUSIONS: From the skeletal
      perspective, patients with Down's syndrome who are in a period of growth
      demonstrate a reduction of the anterior skull base. From the dentoalveolar
      perspective, they show protrusion and proinclination of lower incisors, which is
      related to a tendency to anterior cross-bite and, to a lesser extent, to
      diminished overbite. Likewise, the lower lip protrusion observed in this study is
      related to the position of the lower incisor.

PMID- 12195303
TI  - Rib fractures after chest physiotherapy for bronchiolitis or pneumonia in
      infants.
AB  - BACKGROUND: The reported causes of rib fractures in infants are: child abuse,
      accidental injury, cardiopulmonary resuscitation, bone fragility, birth trauma
      and severe cough. OBJECTIVE: To report chest physiotherapy (CPT) as a new cause
      of rib fractures in five infants. MATERIALS AND METHODS: We retrospectively
      identified all infants with rib fractures after CPT for bronchiolitis or
      pneumonia over a 4-year period in two paediatric and one paediatric radiology
      units in three university hospitals in Paris. RESULTS: Five boys were identified.
      Their median age was 3 months. None had any other potential cause of rib
      fractures. The indication for CPT was bronchiolitis in four cases and pneumonia
      in one. The median number of rib fractures was four (range 1-5). Fractures were
      located between the 3rd and 8th ribs; they were lateral in four patients and
      posterior in one; they were unilateral in four patients and bilateral in one.
      Evolution was favourable in all cases. The prevalence of rib fractures after CPT
      during the study period was estimated at 1 in 1,000 infants hospitalised for
      bronchiolitis or pneumonia. CONCLUSIONS: CPT should be considered a potential,
      but very rare cause of rib fractures in infants. It can be of clinical relevance
      when rib fractures are the only feature suggestive of child abuse.

PMID- 12195304
TI  - Pediatric postprimary pulmonary tuberculosis.
AB  - BACKGROUND: Postprimary pulmonary tuberculosis (TB) is not commonly seen in
      children. OBJECTIVE: The purpose of this study was to determine the radiographic
      findings and patient characteristics of pediatric postprimary pulmonary TB.
      MATERIALS AND METHODS: We reviewed the clinical charts and chest radiographs in
      six patients. RESULTS: The radiographic findings of pediatric postprimary
      pulmonary TB include upper-lobe consolidation and cavitation, multifocal ill
      defined airspace opacities, evidence of prior pulmonary TB, and apical pleural
      thickening. Pleural effusions and lymphadenopathy are not commonly present.
      Although postprimary disease typically does not affect young children, five of
      the children in this series were less than ten years of age at the time of
      presentation. CONCLUSION: The possibility of postprimary TB should be considered
      in pediatric patients at risk for this disease who present with upper-lobe
      pulmonary consolidation and cavitation. These patients are highly infectious and
      early recognition and treatment can limit transmission of TB.

PMID- 12195306
TI  - Improving the diagnosis of acute appendicitis in children with atypical clinical
      findings using the technetium-99m hexamethylpropylene amine oxime-labelled white
      blood-cell abdomen scan.
AB  - BACKGROUND: Diagnosing acute appendicitis in children with equivocal signs and
      symptoms may be difficult. The usual approach is hospital observation and
      frequent re-examination. However, many surgeons are reluctant to delay surgery
      because of the risk of perforation and a negative laparotomy. OBJECTIVE: To
      assess and compare the value of the technetium-99m hexamethylpropylene amine
      oxime ((99m)Tc-HMPAO)-labelled white-blood-cell (WBC) abdomen scan in the
      diagnosis of acute appendicitis in children with atypical clinical presentation.
      PATIENTS AND METHODS: Fifty children with acute right lower quadrant abdominal
      pain and possible acute appendicitis, but atypical findings were included. After
      IV injection of (99m)Tc-HMPAO-labelled WBCs, serial anterior abdomen scans were
      obtained using a gamma camera. RESULTS: Thirty-three children underwent surgery,
      while 17 children were managed conservatively and were followed up for at least 1
      month. Four children had false-positive results and one child had a false
      negative scan result. The overall sensitivity, specificity, accuracy, positive
      predictive value and negative predictive value of the scan to diagnose acute
      appendicitis in children with atypical findings was 96.7, 80.0, 90.0, 87.8 and
      94.1%, respectively. CONCLUSIONS: The (99m)Tc-HMPAO WBC abdomen scan is a
      potential tool for diagnosing acute appendicitis in children with atypical
      clinical findings. The high sensitivity and negative predictive value allows
      early discharge from the emergency department to avoid costly observation in
      hospital and potentially unnecessary surgery in those patients with negative
      scans.

PMID- 12195305
TI  - Interventional radiology techniques for the diagnosis of lymphoma or leukemia.
AB  - BACKGROUND: Fluid aspiration, percutaneous biopsy, and catheter drainage are
      standard minimally invasive methods of diagnosing lymphoma or leukemia in adults.
      OBJECTIVE: To determine the effectiveness of interventional radiologic techniques
      in diagnosing specific hematologic malignancies in children. METHODS: During a 4
      year period, 22 patients (16 male, 6 female; median age, 13 years) underwent 25
      percutaneous biopsies, 6 fluid aspirations, 3 catheter drainages, and 1 needle
      localization for diagnosing suspected hematologic malignancy. RESULTS: For
      Hodgkin's disease, the procedures yielded 6 true-positive (TP) results, 2 true
      negative (TN) results, and 2 false-negative (FN) results; for non-Hodgkin
      lymphoma (NHL), 14 TP results, 1 TN result, and 3 FN results; and for leukemia, 4
      TP results and 3 FN results. Percutaneous biopsies yielded 16 TP results, 3 TN
      results, and 6 FN results. Aspirations and drainages yielded 8 TP results and 1
      FN result. The one needle localization yielded a FN result. Overall sensitivity
      was 75%+/-7.3%; specificity, 100%; and accuracy, 77%+/-7.1%. CONCLUSION:
      Percutaneous biopsy of lymphoma is usually diagnostic. Drainage or aspiration of
      a fluid collection associated with NHL or leukemia is often diagnostic and is
      less invasive than biopsy. These procedures are minimally invasive and effective
      for diagnosing pediatric hematologic malignancies.

PMID- 12195307
TI  - Skeletal measurements among infants who die during the perinatal period: new
      population-based reference.
AB  - BACKGROUND: Reference data for roentgen skeletal measurements among infants who
      die during the perinatal period is not available, although it might prove helpful
      in the study of pre-autopsy radiographs. OBJECTIVE: Our aim was to define new
      population-based reference data for skeletal measurements among infants who die
      during the perinatal period. MATERIALS AND METHODS: We routinely took
      standardised pre-autopsy radiographs of aborted and stillborn fetuses from 16
      weeks gestational age to 7 days after delivery during a period of 11 years in our
      hospital. The data presented here represents nearly all perinatal deaths in a
      well-defined geographical area during the study period. We calculated detailed
      plots of estimated 10th-90th centiles and quartiles of different skeletal
      measurements by gestational age at death. RESULTS: High correlations were seen
      between birth weight and the different skeletal measurements, including cranial
      width ( r>0.9, P<0.001). We were not able to identify any asymmetrical pattern of
      skeletal growth. Reference plots for femoral, tibial, humeral, radial and lumbar
      spine lengths, and for pelvic width are presented. CONCLUSIONS: We suggest that
      the current population-based reference data might be beneficial, and that
      skeletal radiographic measurements might contribute substantially in the
      assessment of fetal growth stage and in detection of skeletal abnormalities in
      infants who die during the perinatal period.

PMID- 12195308
TI  - Mesenteric mass in a young girl--an unusual site for Gaucher's disease.
AB  - We report the first case of a child with Gaucher's disease and a large mesenteric
      mass, confirmed histologically to be Gaucher's cell infiltrates. We describe the
      radiological findings and discuss further management. The advent of enzyme
      replacement therapy has prolonged survival and the emergence of previously
      undocumented manifestations of the disease is being observed. The radiologist and
      clinician should be alert to the possible development of these new problems and
      the fact that in Gaucher's disease a palpable right upper-quadrant mass need not
      necessarily represent hepatomegaly.

PMID- 12195309
TI  - Tuberous sclerosis with cystic renal disease and multifocal renal cell carcinoma
      in a baby girl.
AB  - An infant, in whom the prenatal diagnosis of tuberous sclerosis complex was made,
      presented with extreme bilateral nephromegaly owing to diffuse cystic changes.
      Histology of the resected non-functioning left kidney revealed, in addition to
      the characteristic cysts, two foci of renal cell carcinoma not visible on US or
      MRI. This infant is exceptional given the extensive cystic transformation of both
      kidneys and the presence of malignant lesions at this young age.

PMID- 12195310
TI  - Sonographic diagnosis of multiple small-bowel intussusceptions in Peutz-Jeghers
      syndrome: a case report.
AB  - Peutz-Jeghers syndrome (PJS) is a rare, though well-described, hereditary
      polyposis syndrome associated with mucocutaneous pigmentation that typically
      presents in the second decade of life with complications related to intestinal
      polyps. We present two cases of teenaged girls presenting with small-bowel
      intussusceptions within a 3-month period. Sonographic examinations readily
      revealed small-bowel intussusceptions with secondary small-bowel obstruction. In
      both the symptoms were less severe than one would expect given the underlying
      pathology found at subsequent surgery. Sonographic imaging with pathologic
      correlation is provided.

PMID- 12195311
TI  - Neonatal, severe primary hyperparathyroidism: a 7-year clinical and radiological
      follow-up of one patient.
AB  - Neonatal primary hyperparathyroidism is a rare entity characterized by marked
      hypercalcemia, diffuse parathyroid hyperplasia, and skeletal demineralization. It
      is often lethal unless total parathyroidectomy is performed. Long-term outcome of
      treated patients is poorly documented. We report the clinical and radiographic
      outcome of this disease in a 7-year-old boy who underwent a total
      parathyroidectomy and autotransplantation of a fragment of one parathyroid gland
      to his thigh in the neonatal period. This paper demonstrates the importance of
      prompt diagnosis and management in neonatal hyperparathyroidism and the role of
      various imaging modalities in its diagnosis and follow-up.

PMID- 12195313
TI  - [How well-informed is the ophthalmology patient?].
AB  - BACKGROUND: The patient responsibility concept is based on better informed
      patients who can shoulder the responsibility for their own health and who can
      discuss matters competently with their health care provider, becoming partners of
      their doctors in enabling them to make informed decisions about their medical
      care. Better patient information and more active participation is also often
      associated with greater patient satisfaction, improved compliance with treatment
      and therefore better quality as well as reduced cost health care. The aim of this
      study was to evaluate how well informed the ophthalmic patient is before visiting
      the ophthalmologist and what are his needs for additional information. MATERIALS
      AND METHODS: 106 patients seen in four ophthalmic practices in Switzerland
      completed a specifically developed and validated questionnaire. We recorded
      demographic and eye disease information, the time spent to get the information,
      the sources used, the degree of satisfaction achieved, the patient need for
      information as well as the sources and contents preferred. RESULTS: Only 36.8 %
      of the patients collected information prior to their ophthalmic consultation.
      Other physicians (50 % of the cases) and other patients (33.3 % of cases) were
      the most frequent information sources. Information was mainly collected about the
      ophthalmologist (61.8 % of the cases), and about the own eye diseases (20.6 %).
      Only 2.8 % of the patients spent more than 3 hours looking for information. 94.7
      % of the patients wished to be orally informed in the practice. 74.7 % preferred
      to be informed only or also by the physician. CONCLUSIONS: Most ophthalmic
      patients do not represent the ideal of an informed patient. Without additional
      education they do not appear to have the knowledge or skill required for taking
      the responsibility for their own health.

PMID- 12195312
TI  - [The pathogenesis of herpetic keratitis].
AB  - BACKGROUND: Viral infections of Herpes origin are the most commonly encountered
      ones in man. The most important member of this family is the Herpes simplex virus
      (HSV), two varieties of which are known to exist: HSV-1 affects predominantly the
      upper half of the body, whereas HSV-2 is associated mainly with diseases of the
      urogenital tract. In the immunocompetent host, viral replication is usually
      confined to cutaneous and mucocutaneous sites, invasion of subcutaneous tissues
      being impeded by an early onset of non-specific defence mechanisms. These are
      rapidly complemented by the specific, mainly cellular, immune response. PATIENTS:
      Epithelial dendritic keratitis is the first symptomatic clinical finding, and
      after several recurrences, the corneal stroma may become involved. This condition
      of herpetic stromal keratitis (HSK), which, in contrast to the epithelial one, is
      believed to be directed by a predominantly immunopathological process, is one of
      the leading causes of infectious blindness in developed countries. RESULTS: The
      mechanisms underlying HSK, and the establishment of viral latency and
      reactivation are poorly understood. But on the basis of studies with mice as well
      as clinical immunohistological observations, evidence is now accumulating in
      support of a cell-mediated mechanism being responsible for corneal destruction.
      CONCLUSION: Our present knowledge of the pathogenesis of herpetic keratitis is
      incomplete. The different pathophysiological aspects reflecting our current
      understanding, such as that of a virally induced autoimmune disease, form the
      basis of accepted clinical treatment concepts.

PMID- 12195314
TI  - [Transplantation of the submandibular gland in absolute dry eyes. Effect on the
      ocular surface].
AB  - BACKGROUND: In absolute dry eyes the use of pharmaceutical lubricants can be
      insufficient to prevent progressive conjunctival and corneal epitheliopathy and
      the severe symptoms associated. In this situation a microvascular autologous
      submandibular gland transplant can be used to continuously provide a natural tear
      substitute. We studied the effect of this salivary tear film on the ocular
      surface in a prospective controlled clinical study. PATIENTS AND METHODS: We
      examined 20 eyes with a viable submandibular gland transplant and 20 severely dry
      eyes without or with a nonviable transplant as a control for the first
      postoperative year. Visual acuity, baseline-tear secretion, fluorescein break-up
      time and slit-lamp microscopical grading of ocular surface features, Rose Bengal
      staining and conjunctival impression cytology were evaluated. RESULTS:
      Postoperatively baseline-tear secretion and break-up time were significantly
      better in the group with a viable submandibular gland transplant than in the
      controls. The biomicroscopical staging of eyes with a salivary tear film was
      stable or showed a trend to improvement, while controls showed a trend to
      deteriorate. A successful submandibular gland transplant reduced the conjunctival
      and corneal neovascular hyperaemia. However, in 6 eyes with an excessive salivary
      epiphora, a microcystic epithelial oedema was observed. The epiphora and the
      associated oedema could be successfully controlled by means of a surgical
      reduction of the transplant. CONCLUSIONS: Following successful autologous
      submandibular gland transplantation lubrication and comfort are significantly
      improved and the ocular surface is stabilised during the first postoperative
      year. Severe preoperative morphological alterations and the salivary character of
      the new tear film prevent a more obvious improvement of the ocular surface.

PMID- 12195315
TI  - [Tear-film deficiencies in patients with sarcoidosis; clinical study of 56
      patients].
AB  - BACKGROUND: The eye and its adnexa are frequently involved in sarcoidosis.
      Keratoconjunctivitis sicca is a typical manifestation that is believed to result
      from aqueous-layer deficiency in context with lacrimal gland disease. In this
      study we determined which layer of the tear-film might be involved. PATIENTS AND
      METHODS: Fifty-six patients with clinically and histologically proven sarcoidosis
      were prospectively analysed for symptoms of dry eye, visual acuity, signs of
      blepharitis, Schirmer II test, rose bengal test, fluorescein staining, break-up
      time (BUT), and impression cytology (IPC). Deficiencies of the lipid, water and
      mucin layers were differentiated. The observations were compared with those from
      a control group of patients with symptoms of "dry eye" (n = 56). RESULTS: All
      patients in the control group, but only 20 sarcoidosis patients had dry eye
      symptoms. The BUT in the control group (7.2 +/- 5.4; mean +/- SEM) was shorter (p
      < 0.02) than in sarcoidosis patients (8.9 +/- 4.5; mean +/- SEM). Compared with
      the sarcoidosis patients, conjunctivitis occurred more frequently in the control
      group (p < 0.01). Rose bengal staining was positive in 18 sarcoidosis patients,
      and in 35 patients of the control group (p < 0.01). Signs of blepharitis, the
      results of Schirmer test, fluorescein staining and IPC, and the frequent
      incidence of deficiencies of aqueous layer, lipid layer and combined deficiencies
      of two or more layers did not differ significantly between the two groups.
      Deficiencies of the mucin layer were detected in 43 sarcoidosis patients, and in
      51 patients in the control group (p < 0.05). CONCLUSIONS: Tear-film deficiencies
      are common in sarcoidosis patients, even when clinical symptoms are absent.
      Observations herein suggest that patients with sarcoidosis may not only suffer
      from deficiencies of the aqueous layer, but also of the mucin and lipid layers.

PMID- 12195316
TI  - [Satisfaction with low vision aids].
AB  - PURPOSE: To study satisfaction with the prescription of low vision aids (LVA) and
      to correlate LVA with eye disease and visual function one year after
      prescription. METHODS: A questionnaire was sent out to 576 patients who had
      received LVAs in 1998. We evaluated their subjective satisfaction with the LVA as
      well as with the whole examination in our low vision department and compared the
      kind of LVA with disease and visual acuity. In addition, we observed whether
      additional functional deterioration led to problems with the LVA. RESULTS: 301
      questionnaires were returned (52 %). They reported on high satisfaction with the
      management and the LVA (> 90 %). 57 % used their optical LVAs more than 5 times
      daily mostly for reading and writing (74 % and 78 %, respectively). However, 20
      patients were no longer able to read with their LVA due to decrease of function.
      When comparing the LVAs, most patients with age-related macular degeneration were
      supplied with magnifiers (30 %). Thirty percent of the patients supplied with
      CCTVs (43 %; visual acuity 0.02 to 0.3) used the CCTV daily. CONCLUSIONS: The
      majority of low vision patients is very satisfied with the prescription of LVAs
      and frequently uses these aids. The adequate LVA is a major factor improving the
      quality of life. However, due to the possibility of greater deterioration after
      the disease, follow-up examinations on a regular basis appears to be necessary.
      The early prescription of CCTVs often helps to preserve the reading ability and
      should therefore be kept in mind by the physician dealing with low vision
      patients.

PMID- 12195318
TI  - [Rhegmatogenous PVR detachment: long-term results after extraocular minimal
      scleral buckling].
AB  - BACKGROUND: To present the long-term anatomical and functional results and the
      dynamics of proliferative vitreoretinopathy (PVR) after precise segmental scleral
      buckling without drainage, known as extraocular minimal surgery. PATIENTS AND
      METHODS: In a prospective study 172 consecutive rhegmatogenous PVR detachments
      were included which were operated on between January 1994 and February 1996 at
      the Department of Ophthalmology, Higher Medical Institute, Plovdiv, Bulgaria,
      with cryopexy and segmental scleral buckling without drainage. The follow-up
      ranged between 54 and 79 months (xmacr; 5S years). In 43 eyes was a PVR stage A,
      in 50 stage B, in 60 stage CP, and in 19 a PVR stage CA. All detachments were
      studied precisely for retinal breaks pre- and intraoperatively and the breaks
      tamponaded by a precise buckle. RESULTS: 1. Anatomical results: Complete retinal
      reattachment in 145 eyes (84 %) after 1 operation and in 148 eyes (86 %) after
      reoperation, residual tractional detachment with reattached macula in 12 eyes (7
      %) and detachment due to progression of PVR in 12 eyes (7 %). 2. Functional
      results: Postoperative visual acuity ranged between 0.3 and 1.0 in 111 eyes after
      xmacr; 5S years. 3. Dynamics of PVR: In 113 detachments (65,7 %) PVR regressed
      completely and in 12 (7 %) it progressed; among these were 8 eyes with
      preoperative PVR-CA and 4 eyes with PVR-CP. CONCLUSIONS: Treatment of PVR
      detachments with nondrainage and minimal buckling provides good anatomical
      results with macular reattachment in 93 %, resulting in good long-term visual
      function. Results were best in detachments with PVR stage A, B and CP.

PMID- 12195317
TI  - [Intravitreal injection of rt-PA and gas in the management of minor submacular
      haemorrhages secondary to age-related macular degeneration].
AB  - BACKGROUND: Subfoveal haemorrhage is a serious complication of choroidal
      neovascularization in age-related macular degeneration (ARMD). Recent studies
      have demonstrated that intravitreal injections of the fibrinolytic agent
      recombinant tissue plasminogen activator (rt-PA) and expansile gas may be
      effective in displacing submacular blood and facilitating visual improvement.
      However, in most of these studies, this technique has been used for the
      management of major haemorrhages. The purpose of our study was to investigate the
      efficacy of treating minor subfoveal haemorrhages with intravitreal rt-PA and
      pneumatic displacement. PATIENTS AND METHODS: In a prospective study, 25
      consecutive eyes of 25 patients with recent (</= 28 days) subfoveal haemorrhage
      secondary to ARMD and severe visual loss were treated with intravitreous
      injections of rt-PA (50 micro g) and sulfur hexafluoride (0,5 ml). The extent of
      the haemorrhage ranged from R to 2 disc areas. Patient follow-up ranged between 4
      and 18 months. RESULTS: Best postoperative visual acuity compared with
      preoperative visual acuity was improved by two or more Snellen lines in 11 of 25
      eyes (44 %). Seven eyes (28 %) maintained this level at the final visit. Duration
      of haemorrhage was associated with a better gain of lines of vision. In a
      subgroup of 9 eyes with duration of haemorrhage </= 14 days, 7 (78 %) improved by
      two or more Snellen visual acuity lines, whereas only 4 of 16 eyes (25 %) with
      duration of haemorrhage > 14 days showed a comparable outcome (p = 0.017). There
      were no side effects or complications. CONCLUSIONS: Our findings suggest that
      intravitreous injections of rt-PA and sulfur hexafluoride are of value for an
      improved and accelerated visual recovery in ARMD patients with minor subfoveal
      haemorrhages. Duration of haemorrhage </= 14 is associated with a better gain of
      lines of vision. Final visual outcome, however, is limited by the underlying
      ARMD. In addition, a rapid displacement of subfoveal haemorrhages may reveal
      discrete choroidal neovascular membranes amenable to further treatment. The
      complication rate of this therapeutic approach appears to be low.

PMID- 12195319
TI  - [Reproducibility of measurements with the retinal vessel analyzer under optimal
      conditions].
AB  - BACKGROUND: [corrected] To evaluate the reproducibility of measurements with the
      Retinal Vessel Analyzer (RVA) in healthy subjects and to describe which measuring
      conditions should be guaranteed to obtain optimal results. METHODS: The diameter
      of retinal arteries and veins of 20 healthy subjects (M : F = 11 : 9; mean age:
      33 +/- 12 years) were measured with the RVA at baseline, after 2 hours, and after
      2 weeks. RESULTS: No statistically significant differences in the diameter of
      retinal arteries and veins between the single measurements were present. Short
      term variability of arterial diameter was 1 %, and the intraclass correlation
      coefficient kappa was 0.96. Long-term variability was 1.8 %, kappa was 0.98. In
      retinal veins, a short-term variability of 1 % was calculated, with a kappa of
      0.97. Long-term variability was 1.5 %, with a kappa of 0.98. CONCLUSION: Due to
      the high reproducibility of its measurements, the RVA appears to be a useful
      device for both analysis and follow-up of retinal vessel diameters.

PMID- 12195320
TI  - [Tubulointerstitial nephritis and uveitis (TINU syndrome) - comorbidity and
      complications in four patients].
AB  - BACKGROUND: TINU syndrome probably is a frequently overlooked disease where
      uveitis occurs in association with acute tubulointerstitial nephritis. Diagnostic
      criteria have been published recently. PATIENTS AND METHODS: In this
      retrospective case series the charts of four consecutive patients with TINU
      syndrome (follow-up 36, 23, 17, and 12 months, respectively) were analysed,
      including comorbidity and complications, and the literature was reviewed.
      RESULTS: Two patients were treated with methotrexate or ciclosporin A and
      mycophenolate mofetil. In one patient autoimmune thyroiditis was known. During
      the follow-up, symptoms indicative of rheumatoid arthritis were observed. Because
      of her uveitis she required methotrexate therapy. Three patients were obese (mean
      BMI 32.2 kg/m (2)). Ocular complications were posterior synechiae (two patients)
      and papillary and macular oedema (three patients). One patient developed
      cerebrospinal hypertension under ciclosporin A treatment which resolved after
      discontinuation of therapy. CONCLUSIONS: Patients with definite TINU syndrome
      frequently suffer from other diseases and associated immune phenomena. The course
      of the disease can vary considerably. Complications do occur, despite overall
      good prognosis. Regional and systemic steroids may be sufficient; frequently
      steroid sparing immunosuppressives are necessary at least temporarily. Patients
      with this multiorgan disease do need to be followed by a paediatrician or a
      medical specialist.

PMID- 12195321
TI  - [Use of memantine in progressive glaucoma. Case report].
AB  - BACKGROUND: Several animal models demonstrated that NMDA-receptor antagonists
      like memantine inhibit the excitotoxic action of glutamate in glaucoma.
      Furthermore, this also enables to slow down the degeneration of retinal ganglion
      cells. In the following case report we investigated the use and tolerability of
      memantine in a glaucoma patient. PATIENT AND METHODS: We report on a 73-year old
      male with progressive glaucoma damage. Treatment with memantine a 20 mg/d lasted
      for 6 months and was preceded by one week a 10 mg/d. Follow-ups with perimetry
      and VEP were performed at beginning and 2, 4, 6 and 12 months after. RESULTS: The
      first control showed an improvement of perimetry. The following examinations
      demonstrated a stabilization of perimetry and VEP. Because of side-effects there
      was no tolerability of a higher dose of memantine a 30 mg/d or continuation of
      the therapy after 6 months. CONCLUSION: Memantine seems to be neuroprotective in
      glaucoma patients. At present a multicentric study is under way. More results may
      be expected shortly.

PMID- 12195322
TI  - [Ocular myasthenic syndrome and systemic lupus erythematosus].
AB  - BACKGROUND: Reports on association of systemic lupus erythematosus (SLE) and
      myasthenia gravis are sparse. CASE REPORT: An 40-year old woman complained of
      sudden onset of diplopia. A SLE was known for 6 years. Both eyes showed a deficit
      in upgaze, the right eye showed a deficit in abduction and a slight ptosis.
      Further ophthalmologic and neurologic status were normal. Magnetic resonance
      tomographic imaging of the brain and the results of the spinal fluid examination
      were unremarkable. Sonographic imaging and magnetic resonance tomographic imaging
      studies showed normal extraocular muscles. The edrophonium test (short acting
      inhibitor of acetylcholinesterase) was positive (elevation of the ptotic lid
      after injection of edrophonium). Acetylcholine receptor antibodies were elevated
      to 70 nmol/l (norm: < 0.25 nmol/l). Thoracic computed tomographic scan showed no
      evidence of a thymoma/thymus hyperplasia or thymus carcinoma. Systemic steroid
      treatment resolved the complaints within weeks. CONCLUSIONS: The patient with SLE
      had an ocular myasthenic syndrome. The etiology of the association of the two
      autoimmune diseases is not clear. SLE patients showing fatigue signs or pareses
      should be examined for myasthenia gravis. Patients with isolated ocular
      myasthenic syndromes should be examined for a generalized immunological disorder.

PMID- 12195324
TI  - The first prospective controlled trial comparing wireless capsule endoscopy with
      push enteroscopy in chronic gastrointestinal bleeding.
AB  - BACKGROUND AND STUDY AIMS: In chronic gastrointestinal bleeding (CGB), bleeding
      sites located in the small bowel are difficult to detect with conventional
      radiological or scintigraphic techniques. Push enteroscopy (PE) is at present
      considered to be the most effective diagnostic procedure. The aim of this
      prospective trial was to compare the efficacy of wireless capsule endoscopy (CE)
      with PE. PATIENTS AND METHODS: Between April and October 2001, 65 patients with
      CGB were referred to our unit. Complete conventional diagnostic work-up
      (including small-bowel enteroclysis, angiography, and scintigraphy), as well as
      PE and CE, were performed in 32 patients. RESULTS: On average, the patients had
      been suffering from CGB for 29 +/- 24 months (6 - 126); the lowest hemoglobin
      level varied between 3.0 and 9.9 g/dl (mean 5.9 +/- 1.4); 17 +/- 18 blood units
      (0 - 60) were transfused. Each patient underwent 6 +/- 7 (range 1 - 38)
      hospitalizations, with a mean of 14 +/- 9 diagnostic procedures before CE was
      used. Conventional diagnostic procedures revealed relevant pathological findings
      in five of the 32 patients (16 %). Definite bleeding sites diagnosed by PE in
      nine patients (28 %) included angiodysplasia (seven patients), small-bowel cancer
      (one patient) and lymphoma (one patient). CE detected the definite source in 21
      of the 32 patients (66 %) ( P < 0.001). Definite bleeding sources included
      angiodysplasia (17 patients), malignant stenoses (two patients) and inflammatory
      small-bowel disease (two patients). Questionable bleeding sources were seen on PE
      in three additional patients (9 %), and using CE in a further seven patients (22
      %). Both CE and PE were safe and were not associated with any morbidity.
      CONCLUSIONS: In the present trial in patients with CGB, wireless CE had the
      highest diagnostic yield and was significantly superior to PE. CE can help reduce
      the number of diagnostic procedures and could become the initial diagnostic
      choice in patients with CGB and negative upper and lower gastrointestinal
      endoscopy.

PMID- 12195325
TI  - Endoscopic variceal ligation plus propranolol vs. transjugular intrahepatic
      portosystemic stent shunt: a long-term randomized trial.
AB  - BACKGROUND AND STUDY AIMS: After a first variceal bleeding episode in patients
      with cirrhosis of the liver, treatment with transjugular intrahepatic
      portosystemic stent shunt (TIPS) and endoscopic variceal ligation (EVL) plus
      propranolol were compared, with regard to prevention of variceal rebleeding,
      complications, and mortality. PATIENTS AND METHODS: 85 patients were randomly
      allocated to receive TIPS (n = 43) or EVL (n = 42). The groups were comparable
      regarding age, sex, etiology of liver cirrhosis, and liver function. RESULTS: The
      mean observation times were 4.1 years in the TIPS group and 3.6 years in the EVL
      group. Although the probability of rebleeding was higher in the EVL group (29.9%)
      than in the TIPS group (19.4%), the difference was not statistically significant.
      Three of five patients of the EVL group successfully underwent TIPS placement
      after treatment failure. The probability of TIPS dysfunction requiring shunt
      revision was 89 %. Hepatic encephalopathy was observed more often in the TIPS
      group (40.5%) than in the EVL group (20.5%; P < 0.05). The probability of
      survival was similar in both groups (TIPS group 75.9%, EVL group 82.2%; n.s.).
      CONCLUSIONS: In view of its good efficacy and the lower cost of treatment,
      endoscopic ligation plus propranolol may be recommended as initial procedure for
      prevention of recurrent variceal hemorrhage, whereas TIPS seems to be the
      preferable procedure in patients with recurrent bleeding after adequate
      endoscopic and pharmacological treatment.

PMID- 12195326
TI  - Evaluation of a virtual endoscopy simulator for training in gastrointestinal
      endoscopy.
AB  - BACKGROUND AND STUDY AIMS: Skills in gastrointestinal endoscopy mainly depend on
      experience and practice. Training on endoscopy simulators may decrease the time
      needed to reach competency in endoscopy. The purpose of the study was to
      determine whether the GI-Mentor, a virtual reality endoscopy simulator, can
      distinguish between beginners and experts in endoscopy and to assess whether
      training improves the performance of beginners. METHODS: A total of 13 beginners
      and 11 experts (more than 1,000 procedures) in gastrointestinal endoscopy were
      included. The baseline assessment consisted of virtual endoscopies and skill
      tests. The beginners were randomly allocated to receive training (n = 7) or no
      training (n = 6). The training group was allowed to practice using the simulator
      for 2 hours per day. After 3 weeks participants were re-evaluated with two new
      virtual endoscopy cases and one virtual skill test. Insertion time, correctly
      identified pathologies, adverse events and skill test performance were recorded.
      RESULTS: The baseline assessment revealed significant differences favoring the
      experts for virtual endoscopies and skill tests. Significant differences in favor
      of experts were found for successful retroflection during
      esophagogastroduodenoscopy (EGD) (P < 0.005); adverse events during colonoscopy
      (P < 0.02); insertion time (P < 0.001); correctly identified pathologies in
      gastroscopy and colonoscopy (P < 0.02); and skill test performance (P < 0.01).
      The final evaluation showed significant differences between training and no
      training groups, in favor of the training group, for the number of adverse events
      during virtual endoscopy (P < 0.04), for the insertion time during colonoscopy (P
      < 0.03); and for skill test performance (P < 0.01). The training group improved
      its abilities on the simulator significantly. Differences between experts and the
      training group were no longer seen. CONCLUSION: This virtual endoscopy simulator
      is capable of identifying differences between beginners and experts in
      gastrointestinal endoscopy. A 3-week training improves the performance of
      beginners significantly. This quite fast improvement in endoscopic skills
      certainly cannot be seen in clinical practice; no conclusions can be made about
      the impact of virtual simulator training on real-life endoscopy, and this must be
      evaluated.

PMID- 12195327
TI  - Tele-endoscopy: influence of data compression, bandwidth and simulated
      impairments on the usability of real-time digital video endoscopy transmissions
      for medical diagnoses.
AB  - BACKGROUND AND STUDY AIMS: Real-time digital video transmission (rtDVT) at an
      acceptable quality through networks has been possible for several years. This
      technique can be used for telemedical applications, such as tele-endoscopy. The
      hypotheses of the present study were that the quality of real-time DVT depends on
      the technical equipment used, and that the resulting image quality influences the
      usability of the system for diagnostic purposes. MATERIALS AND METHODS: An
      experimental network was established between two German referral endoscopy
      centers, using the Asynchronous Transfer Mode (ATM) protocol. At first, rtDVTs of
      routine gastrointestinal video endoscopies were transferred through the network
      for prospective evaluation of the feasibility of the technical equipment and its
      usability for diagnostic tele-endoscopy, based on the video image quality.
      Secondly, the image quality and usability for correct telemedical diagnosis were
      evaluated prospectively in a double-blind experimental setting in relation to
      variations in the methods of data compression used, transmission bandwidths, and
      simulated transmission errors. Fourteen endoscopists evaluated 27 variations of
      an endoscopic video sequence. RESULTS: Compression with the Moving Picture Expert
      Group 2 (MPEG2 [4 : 2 : 2]) standard, the ATM protocol, and a bandwidth of 40
      megabits per second (Mb/s) were used successfully in 40 routine tele-endoscopies
      for practical evaluation. Doctors were able to handle the system with ease, and
      its availability was 100%. There were no detectable differences between the
      original video image and the transferred image, and the images were usable for
      diagnosis in all cases. The set-up used clinically was therefore considered to
      provide the optimal conditions for comparisons in the experimental part of the
      study. Experimentally, any technical variation was found to cause a reduction in
      the overall image quality and hence a reduction in diagnostic usability:
      compression algorithm (MPEG2 [4 : 2 : 2] vs. others: P = 0.001), bandwidth (> or
      = 8 vs. < 8 Mb/s: P = 0.001), and error rate (10 (-8) vs. 10 (-7): P = 0.001).
      CONCLUSIONS: rtDVT using MPEG2 [4 : 2 : 2] compression and a bandwidth of 40 Mb/s
      did not effectively differ from the original video images in routine tele
      endoscopy. The qualitative requirements in diagnostic video endoscopy, however,
      are obviously much higher than previously assumed, since experienced endoscopists
      detected a loss of image quality and a reduction in diagnostic usability with any
      reduction in the technical specification. Modern methods of data compression,
      broadband networks and a network protocol with good quality-of-service guarantees
      are therefore prerequisites for diagnostic rtDVT.

PMID- 12195328
TI  - Use of a variable-stiffness colonoscope allows completion of colonoscopy after
      failure with the standard adult colonoscope.
AB  - BACKGROUND AND STUDY AIMS: Experts fail to reach the cecum in 2 - 10% of
      colonoscopies. The purpose of this case series was to evaluate the efficacy of a
      small-caliber, variable-stiffness colonoscope in patients with incomplete
      colonoscopy. PATIENTS AND METHODS: The variable-stiffness colonoscope (Olympus
      America XPCF-140AL) was used by the same examiner to reattempt colonoscopy
      immediately in all patients in whom colonoscopy to the cecum with the standard
      colonoscope was incomplete. RESULTS: Sixteen of 385 attempted colonoscopies
      (4.2%) did not reach the cecum with the standard colonoscope due to looping (n =
      12), fixed angulation of the sigmoid colon (n = 3), and diverticulosis (n = 1).
      The procedures were deemed a failure after a mean of 28 min, despite the use of
      abdominal pressure and positional change in all patients. Fifteen of the 16
      patients (94 %) had a complete colonoscopy with the variable-stiffness
      colonoscope. One patient had an incomplete colonoscopy with the variable
      stiffness colonoscope due to an obstructing mass in the transverse colon that was
      not reached by the standard colonoscope. With the variable-stiffness colonoscope,
      the mean time to cecal intubation was 10.3 min; four patients (25 %) required a
      change in patient position, and six patients (37.5 %) required abdominal
      pressure. CONCLUSIONS: A variable-stiffness colonoscope allowed completion of
      colonoscopy in all patients without obstruction who had an incomplete colonoscopy
      with the standard colonoscope. Further study is needed to determine whether the
      variable-stiffness colonoscope should be used routinely for colonoscopy.

PMID- 12195329
TI  - Endoscopic ultrasound-guided pancreatic duct aspiration: diagnostic yield and
      safety.
AB  - BACKGROUND AND STUDY AIMS: Endoscopic ultrasound (EUS)-guided fine-needle
      aspiration provides useful diagnostic material in solid and cystic pancreatic
      lesions. It is logical that EUS-guided pancreatic duct aspiration may be useful
      in cases of suspected intraductal or duct-obstructing tumors. We evaluated the
      safety and efficacy of EUS-guided pancreatic duct aspiration. PATIENTS AND
      METHODS: Twelve patients with dilated pancreatic ducts underwent EUS-guided duct
      aspiration. Aspirates were submitted for cytology and mucin staining. Patients
      were followed for up to 13 months. RESULTS: There were no procedure-related
      complications. Cytology was diagnostic in nine of the 12 patients (six with
      intraductal papillary mucinous tumor, one with pancreatic clonorchiasis, and two
      with obstructing solid pancreatic adenocarcinomas). Cytology in the remaining
      three patients, all with solid obstructing masses, was nondiagnostic. Overall,
      the diagnostic yield was 75%; however, the yield was 100% in patients without
      extrinsic obstruction. CONCLUSION: This preliminary experience suggests that EUS
      guided pancreatic duct aspiration is safe and can provide diagnostic material in
      a significant number of patients with unexplained pancreatic duct dilation.

PMID- 12195330
TI  - Evaluation of endoscopic retrograde cholangiopancreatography under conscious
      sedation and general anesthesia.
AB  - BACKGROUND AND STUDY AIMS: In adults, general anesthesia is usually only provided
      during endoscopic retrograde cholangiopancreatography (ERCP) when prior attempts
      using conscious sedation have failed. It was hypothesized that in our hospital,
      other factors might be associated with general anesthesia for ERCP. The aim of
      this study was therefore to assess the indications for ERCP under general
      anesthesia, and to evaluate the underlying diseases, type, and efficacy of ERCP
      under general anesthesia in comparison with conscious sedation. PATIENTS AND
      METHODS: We retrospectively analyzed 1,056 ERCPs that had been carried out with
      the patients under general anesthesia or conscious sedation. The indications for
      general anesthesia were recorded, and the underlying diseases, the type and
      success of the interventions, and the causes of premature ERCP termination in
      both groups were assessed. RESULTS: Eighteen percent of the ERCPs were performed
      under general anesthesia and 82% under conscious sedation. The indications for
      general anesthesia were related to the type of procedure planned (46%), premature
      termination of ERCP under conscious sedation (28%), and other reasons. Patients
      with primary sclerosing cholangitis and liver transplant recipients received
      general anesthesia more frequently (general anesthesia vs. conscious sedation,
      36% vs. 16%, P < 0.0001 and 22% vs. 13%, P = 0.003). Conscious sedation was
      provided more frequently in patients with neoplasms and cholelithiasis (21% vs.
      12%, P = 0.004 and 13% vs. 3%, P < 0.001). Painful dilations were performed more
      frequently with the patients under general anesthesia (60% vs. 19%, P < 0.001),
      whereas major papillotomies were preferably performed with conscious sedation
      (34% vs. 21%, P = 0.006). More interventions per ERCP were performed with the
      patient under general anesthesia compared to conscious sedation (P < 0.001),
      during the same time (51 +/- 28 min vs. 52 +/- 26 min, P = 0.39). With conscious
      sedation, the ERCP failure rate was double that with general anesthesia (7% vs.
      14%, P = 0.012), mainly due to inadequate conscious sedation (61%). CONCLUSIONS:
      The frequent use of general anesthesia for ERCP at our institution is related to
      the underlying diseases, which are frequently treated with complex and painful
      ERCP procedures. The efficacy of ERCP with general anesthesia supports a
      continued preference for general anesthesia rather than conscious sedation when
      complex and painful interventional ERCP procedures are planned.

PMID- 12195331
TI  - The use of simulators for training in GI endoscopy.

PMID- 12195332
TI  - Methemoglobinemia induced by topical benzocaine: a warning for the endoscopist.
AB  - Benzocaine is used routinely for topical pharyngeal anesthesia prior to upper
      endoscopy, to improve patient tolerance. A potentially fatal, although often
      unrecognized, complication of benzocaine use is methemoglobinemia. Here, we
      report a case of methemoglobinemia induced by benzocaine given before upper
      endoscopy. Rapid recognition of this complication and immediate treatment is
      essential to prevent complications related to significant tissue hypoxia. This
      case serves as an important reminder to physicians, especially endoscopists,
      about this serious side effect. Furthermore, we question the need for topical
      anesthesia for upper endoscopy in sedated patients.

PMID- 12195333
TI  - Push enteroscopy for recurrent gastrointestinal hemorrhage due to jejunal
      anastomotic varices: a case report and review of the literature.
AB  - Small-bowel anastomotic and adhesion-related varices can form within adhesions in
      the setting of mesenteric venous hypertension, arising from either mesenteric
      venous obstruction or portal hypertension. In evaluating gastrointestinal
      bleeding in patients who have had previous abdominal surgery and mesenteric
      venous hypertension, small-bowel anastomotic varices and adhesion-related varices
      should be considered. For patients with recurrent, severe melena or hematochezia,
      we recommend that the initial diagnostic work-up should include push enteroscopy
      in patients with previous small-bowel surgery. Retrograde ileoscopy should also
      be considered these patients to look for distal small-bowel varices. Potentially,
      such small-bowel varices can be identified by wireless capsule endoscopy. We
      report a case of recurrent gastrointestinal bleeding caused by jejunal
      anastomotic varices which were secondary to superior mesenteric vein occlusion
      following an abdominal gunshot wound. Although the treatment of segmental varices
      has been surgical resection, for patients with overt systemic portal
      hypertension, a transjugular intrahepatic portal-systemic shunt or a
      decompressive shunting procedure are recommended.

PMID- 12195334
TI  - Superficial depressed-type cancer monitored by colonoscopy through the early
      phase of invasion.
AB  - Although previous retrospective reports have demonstrated the developmental
      course of several colorectal tumors, the natural history and progression of
      depressed carcinoma, especially in the early stage, remains obscure. We report a
      case of superficial depressed tumor in the transverse colon in a 71-year-old man,
      which did not change in size and gross configuration through prospective
      colonoscopic observation over a period of 19 months but which was finally
      diagnosed as early-stage submucosal invasive cancer. Most depressed cancers have
      been supposed to arise de novo and grow rapidly, showing aggressive behavior when
      10 mm or less in size. However, this case report may suggest that even a
      depressed tumor may grow to approximately 10 mm within the mucosal layer over a
      few years and that the growth of colorectal tumors, whether they are polypoid or
      depressed in configuration, might be fairly slow.

PMID- 12195335
TI  - What sort of endoscopist for the endoscopy of the future?

PMID- 12195337
TI  - Adenoma without dysplasia: what does it mean?

PMID- 12195339
TI  - Endoscopic hemoclip treatment for bleeding artificially induced Mallory-Weiss
      tears.

PMID- 12195340
TI  - Intussusception of appendiceal adenoma mimicking invasive carcinoma.

PMID- 12195341
TI  - A rare but fatal cause of ulcerative colitis.

PMID- 12195342
TI  - Biliary mucosal bridges.

PMID- 12195343
TI  - Cut guide wire during endoscopic sphincterotomy.

PMID- 12195344
TI  - Immunofluorescence analysis of poliovirus receptor expression in Peyer's patches
      of humans, primates, and CD155 transgenic mice: implications for poliovirus
      infection.
AB  - Oral transmission of poliovirus is restricted to humans and certain primate
      species. The expression of the human poliovirus receptor (CD155) within
      gastrointestinal-associated lymphoid tissues from species that are susceptible
      (human) or resistant (rhesus macaque and CD155 transgenic [Tg] mice) to oral
      poliovirus infection was examined. Sensitivity to oral infection correlated with
      CD155 expression not only in the intestinal epithelium, including the follicle
      associated epithelium (FAE) and microfold (M) cells of Peyer's patches, but also
      in germinal centers within the Peyer's patches. CD155 expression in rhesus
      macaques was reduced in FAE and, significantly, absent in germinal centers. In
      CD155 Tg mice, CD155 expression was barely observable in the intestinal
      epithelium, absent in germinal centers, but prominent in the tunica muscularis.
      This suggests that productive poliovirus infection of the gut is dependent on the
      expression of CD155 within the FAE, including the M cells, and on cells within
      Peyer's patches, most likely within germinal centers.

PMID- 12195345
TI  - Protective immunity after natural rotavirus infection: a community cohort study
      of newborn children in Guinea-Bissau, west Africa.
AB  - To study the natural history of rotavirus infection and to determine the
      protection it confers against reinfection and diarrhea, 200 newborns in Guinea
      Bissau were prospectively followed for up to 2 years. Rotavirus was detected in
      stool specimens collected weekly. By age 2 years, the incidence of primary
      rotavirus infection was 74%. In the first 3 months of life, 17% of the infections
      were diarrhea associated, compared with 60% at 9-11 months; after age 18 months,
      all infections were asymptomatic. A primary infection conferred 52% (95%
      confidence interval [CI], 16% to 73%) and 70% (95% CI, 29% to 87%) protection
      against subsequent rotavirus infection and rotavirus diarrhea, respectively. The
      protection was 66% (95% CI, 24% to 85%) against reinfection within the same
      epidemic, compared with 34% (95% CI, -29% to 67%) against reinfection in any
      subsequent epidemic. The high level of protection against symptomatic rotavirus
      infection provides an important incentive for development of a rotavirus vaccine.

PMID- 12195346
TI  - Comprehensive analysis of human leukocyte antigen class I alleles and cervical
      neoplasia in 3 epidemiologic studies.
AB  - To comprehensively explore the relationship between human leukocyte antigen (HLA)
      class I alleles and cervical neoplasia, a subset of participants from 3 large US
      and Costa Rican cervix studies were typed for HLA class I alleles. Study subjects
      were women with cervical cancer or high-grade squamous epithelial lesions (HSILs;
      n=365) or low-grade squamous epithelial lesions (LSILs; n=275) or who were
      cytologically normal (control subjects; n=681). Allele-disease associations were
      assessed by logistic regression analysis. Consistent associations across all
      studies were observed for HLA-CW*0202 with a combined odds ratio of 0.53 (95%
      confidence interval [CI], 0.29-0.89) for cancer or HSILs and 0.58 (95% CI, 0.37
      1.04) for LSILs, compared with control subjects and adjusted for study. This
      finding supports the hypothesis that a single allele may be sufficient to confer
      protection against cervical neoplasia. Given the relationship between HLA-C and
      its receptors on natural killer (NK) cells, a role is proposed for NK function in
      human papillomavirus infection and cervical neoplasia.

PMID- 12195347
TI  - Low-dose prolonged intermittent interleukin-2 adjuvant therapy: results of a
      randomized trial among human immunodeficiency virus-positive patients with
      advanced immune impairment.
AB  - Twenty-two patients with CD4(+)cell counts <or=200 cells/microL after 12 months
      of stable highly active antiretroviral therapy (HAART; "immunologic
      nonresponders") were randomly assigned to receive subcutaneous low-dose prolonged
      intermittent interleukin (IL)-2 in addition to HAART (n=12) or to continue HAART
      alone (n=10). At 48 weeks of follow-up, no IL-2-related serious adverse events
      and no significant differences in plasma human immunodeficiency virus (HIV) RNA
      level were observed in the 2 groups. A higher incidence of HIV-related clinical
      events was observed among patients receiving HAART alone (3/10) than among
      subjects receiving HAART plus IL-2 (0/12). Significant increases in CD4(+),
      naive, and CD4(+)CD7(+) cells and plasma levels of IL-7 were observed in patients
      receiving IL-2 versus patients receiving HAART alone. A significant increase in
      cell turnover did not lead to a decrease in the frequency of T cell receptor
      excision circles, which remained stable. Rather, increased numbers of T cell
      receptor excision circles per microliter of blood were observed (not
      statistically significant). Thus, adjuvant IL-2 therapy in immunologic
      nonresponders resulted in a clinical benefit, suggesting that the quantitative
      cell recovery involves functionally competent immune cells.

PMID- 12195348
TI  - Impact of human immunodeficiency virus type 1 subtypes on virologic response and
      emergence of drug resistance among children in the Paediatric European Network
      for Treatment of AIDS (PENTA) 5 trial.
AB  - The association between virologic response and human immunodeficiency virus type
      1 (HIV-1) subtype was investigated in 113 HIV-1-infected children randomly
      assigned to receive zidovudine plus lamivudine, zidovudine plus abacavir, or
      lamivudine plus abacavir in the Paediatric European Network for Treatment of AIDS
      (PENTA) 5 trial. Symptomatic children (n=68) also received nelfinavir;
      asymptomatic children (n=45) were randomly assigned to receive nelfinavir or
      placebo. HIV-1 subtypes A, B, C, D, F, G, H, A/E, and A/G were found in 15%, 41%,
      16%, 9%, 5%, 2%, 1%, 5%, and 7% of the children, respectively. Resistance assay
      failure rates were higher for non-B subtypes than for B subtypes (genotype,
      P=.01; phenotype, P=.02). HIV-1 subtype was not associated with virologic
      response at 24 and 48 weeks after initiation of treatment. No differences were
      observed in the frequency of development of resistance mutations L90M (P=1.00)
      and D30N (P=.61) in B and non-B viruses. In conclusion, no evidence that subtype
      determined virologic response to therapy was found.

PMID- 12195350
TI  - Discontinuation of antiretroviral therapy commenced early during the course of
      human immunodeficiency virus type 1 infection, with or without adjunctive
      vaccination.
AB  - Sixteen subjects were treated with highly active antiretroviral therapy within
      120 days of the onset of symptoms of newly acquired human immunodeficiency virus
      type 1 (HIV-1) infection. Eleven of the 16 participated in an adjunctive
      therapeutic vaccine trial. After a mean of 3.2 years of treatment, they elected
      to discontinue therapy. Virus rebound occurred in all subjects and was followed
      by a spontaneous, transient although significant reduction in log plasma HIV-1
      RNA level, ranging from 0.3 to 3.1 log(10) copies/mL. Despite evidence of the
      induction of HIV-1-specific cell-mediated immune responses, plasma viremia was
      not persistently suppressed to <500 copies/mL in any subject. The magnitude and
      dynamics of virus rebound were similar in both vaccinated and unvaccinated
      subjects. Nevertheless, given the transient suppression of viremia observed in
      nearly all subjects after treatment has been discontinued, further investigations
      of adjunctive vaccination with optimized antiretroviral therapy in treating HIV-1
      infection are warranted.

PMID- 12195349
TI  - Durability of response to treatment among antiretroviral-experienced subjects: 48
      week results from AIDS Clinical Trials Group Protocol 359.
AB  - The 24-week extension of AIDS Clinical Trials Group Protocol 359, a study of
      human immunodeficiency virus (HIV)-infected, indinavir-experienced patients, was
      designed to study the durability of "salvage" treatment regimens. Patients
      received saquinavir in combination with either ritonavir or nelfinavir and, in
      addition, delavirdine, adefovir, or both. Patients who demonstrated a virologic
      response at weeks 12-16 were eligible to continue therapy in the extension
      through week 48. Of the 105 eligible subjects who were enrolled in the extension,
      86 (82%) completed 48 weeks, and 49 (57%) of those 86 had HIV RNA levels <or=500
      copies/mL at week 48. For these 86 subjects who completed 48 weeks, the median
      change in CD4 cell count from baseline was +72 cells/mm(3). Greater body weight,
      higher CD4 cell count, and greater degree of phenotypic susceptibility to
      indinavir and saquinavir at baseline were significantly associated with durable
      virologic suppression. These results show that some patients who experience
      treatment failure can demonstrate durable virologic and immunologic responses
      with salvage antiretroviral regimens.

PMID- 12195351
TI  - Serologic responses to epitopes of the major surface glycoprotein of Pneumocystis
      jiroveci differ in human immunodeficiency virus-infected and uninfected persons.
AB  - The major surface glycoprotein (Msg) of Pneumocystis jiroveci (P. jiroveci) is
      important in the immunopathogenesis of Pneumocystis pneumonia (PcP), but is
      difficult to study in humans. We generated 3 overlapping recombinant Msg
      fragments (MsgA, MsgB and MsgC), and analyzed their reactivity with serum samples
      from 95 healthy blood donors and 94 human immunodeficiency virus (HIV)-infected
      persons. Reactivity to the Msg fragments varied with HIV infection and prior
      episodes of PcP but not with geographic origin. Recognition of MsgA was lower-and
      recognition of MsgB was significantly lower-in HIV(+) serum compared with donor
      serum. Serum samples from HIV-positive patients with prior PcP recognized MsgC
      more frequently than did serum samples from those without PcP. None of the serum
      samples drawn from 9 patients before they had developed PcP recognized MsgC.
      These data suggest that these novel recombinant proteins are useful for the
      analysis of antibody responses to Msg.

PMID- 12195352
TI  - Laboratory characterization of methicillin-resistant Staphylococcus aureus in
      Canadian hospitals: results of 5 years of National Surveillance, 1995-1999.
AB  - Two thousand seven hundred eighty single-patient, methicillin-resistant
      Staphylococcus aureus (MRSA) isolates collected between January 1995 and December
      1999 at 17 tertiary care hospital sites across Canada were characterized by
      phenotypic and genotypic techniques. Six clonal types, as defined by pulsed-field
      gel electrophoresis, comprised 87% of all isolates and were labeled Canadian (C)
      MRSA-1 through -6. CMRSA-1 was the most prevalent clonal type, representing 45%
      of all MRSA. CMRSA-2 was indistinguishable from the New York clone and was more
      likely to be associated with community acquisition. CMRSA-3 was more likely to
      cause an infection, compared with the other CMRSA types. CMRSA-4 was
      indistinguishable from epidemic (E) MRSA-16 from the United Kingdom. Both CMRSA-5
      and -6 occurred primarily in single-site, multiyear outbreaks. This study
      confirms that the epidemiology of MRSA in Canada is evolving, but most isolates
      at this time appear to belong to one of a small number of epidemic clones.

PMID- 12195353
TI  - Evidence for a continuum of decreased vancomycin susceptibility in unselected
      Staphylococcus aureus clinical isolates.
AB  - Some Staphylococcus aureus isolates have glycopeptide minimal inhibitory
      concentrations (MICs) in the susceptible range but have subpopulations that grow
      on >or=4 microg/mL vancomycin. Clinical laboratory methods for determining
      susceptibility have proven to be inadequate for detecting these strains. Among
      methicillin-resistant S. aureus (MRSA) and methicillin-susceptible S. aureus
      (MSSA) clinical isolates, 149 (66.2%) of 225 and 17 (56.6%) of 30, respectively,
      grew on brain-heart infusion (BHI) medium containing 2 microg/mL vancomycin; 17
      (7.5%) of the MRSA and 2 (6.6%) of the MSSA isolates grew on BHI screening plates
      containing 4 microg/mL vancomycin. One isolate grew on plates containing 6
      microg/mL vancomycin. This isolate escaped detection by routine testing but had a
      vancomycin MIC of 6 microg/mL when tested in BHI medium. This isolate also had
      decreased Triton X-100-induced autolysis and killing when incubated in broth
      media containing vancomycin, properties accorded to glycopeptide-intermediate S.
      aureus isolates. These observations suggest that glycopeptide-intermediate-like
      S. aureus isolates are circulating undetected and that a continuum of decreased
      susceptibility exists in unselected isolates.

PMID- 12195354
TI  - Activation and transcriptional interaction between agr RNAII and RNAIII in
      Staphylococcus aureus in vitro and in an experimental endocarditis model.
AB  - This study compared the promoter activation profiles of the 2 major transcripts
      of the Staphylococcus aureus global regulon, agr (RNAII and RNAIII). In vitro,
      RNAIII activation temporally followed RNAII activation and was absent in agr
      mutants. In experimental endocarditis, maximal RNAII activation in vegetations
      occurred early, followed by progressive increases in RNAIII activation (P<.05; 2
      vs. 48 h); this paralleled significant increases in vegetation bacterial
      densities over time (P<.05; 2 and 6 vs. 48 h). At 48 h of infection, S. aureus
      densities in vegetations were significantly higher than those in kidney or spleen
      tissue (P<.05), paralleling a significantly greater RNAIII activation profile in
      vegetations than in the latter tissues (P<.05). Of importance, RNAIII activation
      was observed in vegetations in 2 agr mutants. These data demonstrate that RNAIII
      activation in vivo is time and cell density dependent, may be tissue specific,
      and can occur through RNAII-dependent and -independent mechanisms.

PMID- 12195355
TI  - Detection of antibody to Mycobacterium tuberculosis protein antigens in the
      cerebrospinal fluid of patients with tuberculous meningitis.
AB  - Antibodies against Mycobacterium tuberculosis antigens were detected by enzyme
      linked immunosorbent assay in cerebrospinal fluid (CSF) samples obtained from 442
      patients with tuberculous meningitis (TBM) and 102 control patients. Antibodies
      were found in the CSF of 87% of patients with clinical (culture-negative) TBM,
      72% of patients with culture-positive TBM, and 65% of patients with autopsy
      proven TBM. That anti-M. tuberculosis antibodies were detected in the CSF of
      patients with clinically diagnosed cases more frequently than in patients with
      culture-positive cases suggests that the detection of antibodies in CSF tends to
      decrease as bacillary load increases. Of the patients with clinical TBM who were
      coinfected with human immunodeficiency virus (HIV), 70% exhibited anti-M.
      tuberculosis antibody in CSF, which suggests that antibody responses in this
      group were substantially weaker than those in HIV-negative patients with clinical
      TBM. Some groups showed a stronger response to certain antigens, which suggests
      that antigen recognition patterns may be specific for the stage of disease.

PMID- 12195356
TI  - Genotype of 86 Toxoplasma gondii isolates associated with human congenital
      toxoplasmosis, and correlation with clinical findings.
AB  - To study the influence of Toxoplasma gondii genotypes on the severity of human
      congenital toxoplasmosis (asymptomatic, benign, or severe infection or newborn or
      fetal death), 8 microsatellite markers were used to analyze 86 T. gondii isolates
      collected from patients with congenital toxoplasmosis. Seventy-four different
      genotypes were detected, some identical genotypes originating probably from the
      same source of contamination. The 3 less polymorphic microsatellite markers
      associated with 6 isoenzymatic markers allowed a classification of isolates into
      the 3 classical types and detected atypical genotypes. Whatever the clinical
      findings, type II isolates were largely predominant (84.88% in the whole
      collection and 96.49% in 57 consecutive cases). Type I and atypical isolates were
      not found in asymptomatic or benign congenital toxoplasmosis. However, in 4 cases
      in which children were not infected despite isolation of T. gondii from placenta,
      only type I isolates were found.

PMID- 12195357
TI  - Diagnostic criteria and risk factors for Plasmodium ovale malaria.
AB  - Plasmodium ovale is a common malaria parasite in Africa, but the epidemiology of
      P. ovale malaria is poorly known. Exposure to malaria, parasitemia, and morbidity
      were monitored for 6 years among the residents of a village in Senegal. The
      relationship between the level of P. ovale parasitemia and fever risk were
      analyzed, and diagnostic criteria for clinical P. ovale malaria were established.
      Then the relationships between the occurrence of P. ovale clinical malaria and a
      series of entomological, epidemiological, and genetic factors were investigated.
      There was no increased risk of fever when the P. ovale parasite count was <800
      parasites/microL of blood. Of 6621 episodes of illness, 114 (1.7%) were
      attributable to P. ovale. Although most clinical episodes occurred during early
      childhood, a low incidence of the disease persisted among adults. Sickle cell
      trait carriers had increased susceptibility to the disease.

PMID- 12195358
TI  - Human papillomavirus type 16 intratypic variant infection and risk for cervical
      neoplasia in southern China.
AB  - A case-control study was conducted on 1986 Hong Kong women to assess the risk of
      human papillomavirus (HPV) type 16 variants for cervical neoplasia. In total, 255
      women were HPV-16 positive and were analyzed for E6 and E7 sequence variation.
      Two novel substitutions at E6 (T86I and Q116E) and 1 at E7 (R66W) were found.
      Most HPV-16 variants were of Asian (50.6%) or European (44.3%) lineage, and both
      lineages showed similar risk associations for high-grade and invasive cervical
      neoplasia. No increased risk was observed for the subclasses European variant and
      European 350G, which carry a higher risk for invasive cancer in some Western
      populations. The E7 N29S substitution, reported to have a higher risk in Korean
      women, was found equally distributed among normal and various degrees of
      neoplasia. The epidemiology and risk implication of HPV-16 variant infection in
      Hong Kong differ markedly from other parts of the world.

PMID- 12195359
TI  - Association between immune recovery uveitis and a diverse intraocular
      cytomegalovirus-specific cytotoxic T cell response.
AB  - Cytomegalovirus (CMV) causes serious infection in individuals with deficient T
      cell immunity. In acquired immunodeficiency syndrome, the retina is a major site
      of progressive infection, despite the availability of therapy that targets CMV.
      The administration of highly active antiretroviral therapy to suppress human
      immunodeficiency virus frequently results in resolution of CMV retinitis, but
      this may be complicated by ocular inflammation termed "immune recovery uveitis"
      (IRU). To provide insight into the pathogenesis of IRU, the phenotype and
      specificity of intraocular T cells in a single patient were analyzed. The T cell
      infiltrate consisted of a diverse population of CD8(+) CMV-specific T cells, but
      only a minority of these T cells recognized the CMV phosphoprotein 65 and
      immediate early protein 1, which have been considered major targets of the host
      response. These results imply that reconstitution of CMV-specific T cells plays a
      role in IRU and suggest that the specificity of T cells engaged in the control of
      CMV at local sites of reactivation may be broad.

PMID- 12195360
TI  - Eradication of human immunodeficiency virus type 1-infected cells by a
      combination of antimetabolic cytotoxic chemotherapy and antiviral chemotherapy in
      vitro: a pilot study.
AB  - Although highly active antiretroviral therapy against human immunodeficiency
      virus (HIV) type 1 reduces the mortality of persons with acquired
      immunodeficiency syndrome, it does not eliminate HIV reservoirs. In this study,
      which used a 6-thioguanine (6-TG) resistant clone (4C6) of the MT-2 cell line as
      a model, the combination of 6-TG with both reverse-transcriptase (RT) inhibitor
      and protease inhibitor or 6-TG with a protease inhibitor alone completely
      eradicated HIV-1-carrying cells from the culture and protected uninfected 4C6
      cells from HIV-1 infection. The combination of 6-TG and a RT inhibitor,
      azidothymidine, provided partial protection. Protection was extended to human
      peripheral blood mononuclear cells. These results suggest that adding a cytotoxic
      drug in combination antiviral chemotherapy may reduce the establishment of virus
      reservoirs and prevent virus spread. The clinical value of this and similar
      strategies should be further evaluated in HIV-infected patients.

PMID- 12195361
TI  - Factors associated with mortality in human immunodeficiency virus type 1-infected
      adults initiating protease inhibitor-containing therapy: role of education level
      and of early transaminase level elevation (APROCO-ANRS EP11 study). The
      Antiproteases Cohorte Agence Nationale de Recherches sur le SIDA EP 11 study.
AB  - This study attempted to identify factors associated with mortality among human
      immunodeficiency virus (HIV)-infected adults starting a protease inhibitor (PI)
      containing therapy. Among 1155 patients consecutively enrolled in the APROCO
      study between May 1997 and June 1998, clinical characteristics were as follows:
      median age, 36 years; median baseline CD4 cell count, 288 cells/mm(3); and median
      baseline plasma HIV RNA load, 4.4 log(10) copies/mL. After a median follow-up of
      27 months, 48 deaths had occurred, of which 44% were related to acquired immune
      deficiency syndrome. The mortality rate was 2.9% at 12 months. When both data at
      baseline and data at 4 months after the start of PI therapy were considered,
      factors independently associated with mortality were (Cox model) low baseline
      plasma creatinine level, low school education level, low CD4 cell count at 4
      months, low hemoglobin level, and elevated hepatic transaminase levels. Thus,
      social context plus clinical and biologic data, including the 4-month response to
      treatment, must be considered in treatment of HIV-infected patients.

PMID- 12195362
TI  - Pathogenesis of human and bovine Cryptosporidium parvum in gnotobiotic pigs.
AB  - To compare the pathogenesis of human genotype 1 (HuG1) and bovine genotype 2
      (BoG2) Cryptosporidium parvum, neonatal gnotobiotic pigs were given 1-10 HuG1 or
      BoG2 oocysts. The prepatent and patent periods were significantly longer for HuG1
      than for BoG2 C. parvum (prepatent, 8.6 vs. 5.6 days; patent, 16.6 vs. 10.3
      days). BoG2-infected pigs developed significantly more severe disease than did
      HuG1-infected pigs. BoG2 parasites were seen microscopically throughout the
      intestines during the prepatent and patent periods. HuG1 parasites were only
      detected during the patent period in the ileum and colon but colonized the
      mucosal surface in significantly larger numbers than did BoG2. Moderate-to-severe
      villus/mucosal attenuation with lymphoid hyperplasia was seen throughout the
      intestines of BoG2-infected pigs, whereas lesions in HuG1-infected pigs were mild
      to moderate and restricted to the ileum and colon. These findings provide
      additional support for the hypothesis that human and bovine C. parvum genotypes
      may be separate species.

PMID- 12195363
TI  - In vivo switching between variant surface antigens in human Plasmodium falciparum
      infection.
AB  - A semi-immune individual was retrospectively found to have maintained an
      apparently monoclonal and genotypically stable asymptomatic infection for months
      after clinical cure of a Plasmodium falciparum malaria episode. Before the
      attack, the individual had no antibodies to variant surface antigens (VSAs)
      expressed by an isolate (isolate A) obtained at the time of the episode or by a
      genotypically identical isolate (isolate B) obtained from the same individual 3
      months later. Six weeks after the attack, a strong isolate A-specific VSA
      antibody response had developed in the complete absence of isolate B-specific
      antibodies. In contrast, plasma obtained 7 months after the attack contained high
      levels of VSA antibodies recognizing both isolates. This is the first direct
      evidence of in vivo switching between VSAs in human P. falciparum infection. Our
      results suggest that VSA switching is an important survival strategy of P.
      falciparum, enabling the parasite to persist despite protective, parasite
      specific immune responses.

PMID- 12195364
TI  - Beneficial effect of nonsteroidal anti-inflammatory drugs and cyclooxygenase-2
      inhibitors in patients with asthma during viral infection.

PMID- 12195366
TI  - Preemptive therapy for cytomegalovirus infections and the development of
      resistance to ganciclovir.

PMID- 12195368
TI  - The menstrual cycle does not affect human immunodeficiency virus type 1 levels in
      vaginal secretions.

PMID- 12195370
TI  - Association of symptomatic acute human parvovirus B19 infection with human
      leukocyte antigen class I and II alleles.
AB  - To determine the effect of the major histocompatibility complex on the
      development of symptoms during acute human parvovirus B19 infection, we compared
      human leukocyte antigen (HLA) class I and II alleles in 36 patients with
      symptomatic acute B19 infection with those in >900 control subjects from
      northwestern England. The frequency of each of HLA-DRB1*01 (P=.016), DRB1*04
      (P=.007), and DRB1*07 (P<.0001) alleles was significantly higher in parvovirus
      B19 patients than in control subjects. In the parvovirus group, 63.9% carried the
      rheumatoid arthritis-associated shared epitope sequence, compared with 45% of
      control subjects (odds ratio [OR], 2.2; 95% confidence interval [CI], 0.97-4.8;
      P=.04), and carriage was associated with fatigue during the acute phase (OR, 4.2;
      95% CI, 0.8-23.9; P=.047). All symptomatic parvovirus-associated HLA-DRB1
      molecules carry a neutrally charged glutamine at position 10 and a positively
      charged lysine at position 12 of the first hypervariable region. HLA-B49 was
      associated with parvovirus infection independently of HLA-DRB1*01, DRB1*04, and
      DRB1*07.

PMID- 12195372
TI  - Incidence, prevalence, and clearance of type-specific human papillomavirus
      infections: The Young Women's Health Study.
AB  - The natural history of type-specific human papillomavirus (HPV) infections was
      examined in a cohort of 331 women aged 18-35 years who self-referred for routine
      gynecological care. Participants underwent a gynecological examination at
      baseline and at approximately 4 and approximately 10 months after baseline.
      Cervical samples were collected for HPV testing and genotyping at each visit, as
      was information on reproductive, sexual, and medical histories. The rate of new
      HPV infections was 2.9% per month; the highest rates were observed for HPV types
      16, 39, 84, and 51. Among women who tested negative for HPV at baseline, the
      cumulative probability of acquiring an oncogenic HPV strain during a 12-month
      follow-up period was 0.32, compared with 0.18 for nononcogenic strains. Women who
      had had >/=1 new male sex partner in the recent past were significantly more
      likely to acquire a new HPV infection (relative hazard, 2.39; 95% confidence
      interval, 1.20-4.76). The median time to clearance of infection was significantly
      longer for oncogenic strains (9.8 months) than for nononcogenic strains (4.3
      months).

PMID- 12195371
TI  - Identification of a herpes B virus-specific glycoprotein d immunodominant epitope
      recognized by natural and foreign hosts.
AB  - The mapping of linear epitopes of B virus (Cercopithecine herpesvirus 1 and
      herpes B virus) glycoprotein D (gD) was accomplished by screening the constructed
      gD epitope library with serum from B virus-infected macaques. The immunodominant
      epitope, gD (362-370), was identified within the C-terminal region of B virus gD
      that was highly conserved among 19 B virus clinical isolates but was not present
      in either herpes simplex virus (HSV)-1 or HSV-2 gD. A substantial percentage of
      serum samples from macaques (95%) and humans (80%) infected with B virus
      contained antibodies to this epitope. Antibodies against HSV types 1 or 2 did not
      react with this epitope; thus, gD (362-370) has unique potential to detect B
      virus-specific antibody responses in human serum, even in the presence of
      antibodies to HSV-1 and HSV-2.

PMID- 12195373
TI  - The prognostic value of a single hepatitis C virus RNA load measurement taken
      early after human immunodeficiency virus seroconversion.
AB  - Hepatitis C virus (HCV) RNA loads are measured sporadically in HCV-positive
      individuals. However, the prognostic value of these isolated measurements for
      predicting progression to acquired immune deficiency syndrome (AIDS) and all
      cause mortality in coinfected individuals remains unclear. In this study, the
      prognostic value of a single HCV RNA load measurement taken early after human
      immunodeficiency virus (HIV) seroconversion was investigated in a cohort of 96
      male patients with inherited bleeding disorders. Dates of HIV seroconversion had
      been estimated for all patients, and at least 4 HCV RNA load measurements per
      patient were done retrospectively after HIV seroconversion. HCV RNA load
      stabilized at 4 years after HIV seroconversion, and this point was used for
      analysis. There was a significant correlation between increased age and early HCV
      RNA load (r=0.25; P=.01). Adjusting for HIV RNA levels, CD4 cell counts, and the
      age effect, HCV RNA load >5.90 log(10) copies/mL was predictive of progression to
      AIDS and all-cause mortality over a period of at least 15 years.

PMID- 12195374
TI  - Clonal CD8+ T cell expansions in peripheral blood from human immunodeficiency
      virus type 1-infected children.
AB  - The T cell receptor (TCR) repertoires of 24 human immunodeficiency virus (HIV)
      type 1-infected children were determined by flow cytometry in combination with
      sequencing of the highly variable TCR complementarity-determining region 3,
      permitting a quantitative and qualitative assessment of TCR repertoire. Expanded
      subsets of CD8(+) cells expressing a particular TCR beta-chain variable region
      were more commonly identified in HIV-1-infected children than in healthy control
      subjects (75% vs. 13.5%; P<.0001). Older age and lower percentage of CD4(+) cells
      were correlated with expansions. Oligoclonal populations occupied 71%-95% of each
      expanded subset, and predominant clones had high absolute counts. There was
      evidence of functional differentiation to CD28(-) effector cytotoxic T
      lymphocytes, and cells bearing identical TCRs were identified in both CD28(+) and
      CD28(-) cell populations. HIV-1 specificity was observed for expanded clones.
      Children with expansions were not more likely to have increased numbers of CD8(+)
      T cells, a finding consistent with the possibility that the CD8(+) TCR repertoire
      has limited diversity.

PMID- 12195375
TI  - No difference in clinical progression between patients infected with the
      predominant human immunodeficiency virus type 1 circulating recombinant form
      (CRF) 02_AG strain and patients not infected with CRF02_AG, in Western and West
      Central Africa: a four-year prospective multicenter study.
AB  - To compare human immunodeficiency virus (HIV) type 1 disease progression in
      patients infected by the predominant strain circulating recombinant form (CRF)
      02_AG in western and west-central Africa and in patients infected by other
      strains, a prospective multicenter cohort study was conducted in Cameroon and
      Senegal. Among the 335 patients, a broad HIV-1 group M subtype diversity was
      observed in the envelope V3-V5 region, but strain CRF02_AG predominated in both
      Cameroon and Senegal (61.2% and 62.9%, respectively; P<.8). Multivariate analyses
      showed no difference between patients infected by CRF02 strains and those
      infected by other strains in terms of survival (adjusted hazards ratio [HR],
      1.16; 95% confidence interval [CI], 0.76-1.78; P=.5), clinical disease
      progression (HR, 0.79; 95% CI, 0.50-1.25; P=.3), or square root CD4 cell decline
      (regression coefficient, -0.01; 95% CI, -0.82 to 0.81; P=.9). This study suggests
      that the predominance of HIV-1 CRF02_AG strain in western and west-central Africa
      should have no major clinical consequences.

PMID- 12195376
TI  - Clinical course and the role of shiga toxin-producing Escherichia coli infection
      in the hemolytic-uremic syndrome in pediatric patients, 1997-2000, in Germany and
      Austria: a prospective study.
AB  - Hemolytic-uremic syndrome (HUS) is mainly associated with foodborne infections by
      Shiga toxin-producing Escherichia coli (STEC). From January 1997 through December
      2000, 394 children with HUS were evaluated in a prospective multicenter
      surveillance study in Germany and Austria (incidences, 0.7/100,000 and
      0.4/100,000 children <15 years old, respectively). Blood leukocytosis was
      associated with increased detection of STEC in stool cultures (P<.01) and a more
      severe disease course. Risk of death was associated with cerebral involvement
      (P<.01). Most strikingly, non-O157:H7 STEC were detected in 43% of stool cultures
      of patients with HUS: O26 was detected in 15%, sorbitol-fermenting O157:H(-) in
      10%, O145 in 9%, O103 in 3%, and O111 in 43%. Patients with O157:H7 serotypes
      required dialysis for a longer time and had bloody diarrhea detected more
      frequently, compared with patients with non-O157:H7 serotypes (P<.05). This large
      study in children with HUS underlines the rising importance of non-O157:H7
      serotypes, and, despite increased public awareness, the number of patients
      remained unchanged.

PMID- 12195377
TI  - Lethal shock induced by streptococcal pyrogenic exotoxin A in mice transgenic for
      human leukocyte antigen-DQ8 and human CD4 receptors: implications for development
      of vaccines and therapeutics.
AB  - Streptococcal and staphylococcal infections result in significant human morbidity
      and mortality. This study used a transgenic murine model expressing human major
      histocompatibility complex (MHC) class II and human CD4 in which, without
      additional toxic sensitization, human-like responses to the bacterial
      superantigen (SAg) streptococcal pyrogenic exotoxin A (SpeA) could be simulated,
      as determined by studying multiple biologic effects of the SAgs in vivo.
      Expression of human leukocyte antigen (HLA)-DQ8 rendered the mice susceptible to
      SpeA-induced lethal shock that was accompanied by massive cytokine production and
      marked elevation of serum alanine and aspartate aminotransferase levels. Of
      importance, this model enabled examination of the efficacy of an engineered non
      SAg vaccine candidate against SpeA in the context of HLA. This report is thought
      to be the first of a lethal shock triggered in mice by bacterial SAgs without
      prior sensitization and examination of a vaccine against streptococcal SAg in the
      context of human MHC receptors.

PMID- 12195378
TI  - Inflammation and tissue loss caused by periodontal pathogens is reduced by
      interleukin-1 antagonists.
AB  - Periodontal disease is a significant cause of tooth loss among adults. It is
      initiated by pathogenic bacteria, which trigger an inflammatory response that is
      effective in preventing significant microbial colonization of the gingival
      tissues. In some individuals, the reaction to bacteria may lead to an excessive
      host response, resulting in periodontal tissue destruction. Recent developments
      suggest that interleukin (IL)-1 genetic polymorphisms may identify certain
      individuals who have a predisposed susceptibility to periodontal breakdown and
      that elevated levels of IL-1 are found in individuals with periodontal disease.
      However, there is no direct evidence that IL-1 per se is responsible for the
      critical events that occur in periodontitis. We investigated the role of IL-1 in
      periodontal disease in a Macaca fascicularis primate model, using human soluble
      IL-1 receptor type I as a specific inhibitor. The results indicate that
      inhibition of IL-1 alone significantly reduces inflammation, connective tissue
      attachment loss, and bone resorption that are induced by periodontal pathogens.

PMID- 12195379
TI  - Natural resistance-associated macrophage protein 1 polymorphisms are associated
      with microscopy-positive tuberculosis.
AB  - The natural resistance-associated macrophage protein 1 (NRAMP1) is implicated in
      the pathophysiology of mycobacterial infections. We investigated by polymerase
      chain reaction previously published Nramp1 genotypes at 4 loci-INT4, N543D,
      3'UTR, and 5'(CA)(n) microsatellite markers-in 104 human immunodeficiency virus
      negative patients with tuberculosis and 176 healthy control subjects living in
      Denmark. No significant difference in genotype frequency was found between white
      patients with tuberculosis and control subjects (P>.16), but carriage of Nramp1
      variant alleles at loci INT4 and 5'(CA)(n) conferred a significantly increased
      risk of having microscopy-positive compared with microscopy-negative tuberculosis
      (65% vs. 35% [P=.0004] and 63% vs. 38% [P=.047], respectively). The Nramp1
      alleles were not associated with increased risk for the development of cavities
      seen on chest radiographs, or with extrapulmonary tuberculosis. These results
      indicate that variant alleles in the Nramp1 gene are associated with increased
      mycobacterial replication rather than susceptibility for tuberculosis and may
      thus confer increased risk of severe disease.

PMID- 12195380
TI  - Pathogenesis of cerebral Cryptococcus neoformans infection after fungemia.
AB  - The pathogenesis of cerebral infection after Cryptococcus neoformans fungemia in
      outbred mice was investigated. Confocal microscopy and cultures on ficoll-hypaque
      gradient-separated blood cells were used to detect yeasts in the cytoplasms of
      monocytes. In semithin brain sections, poorly capsulated yeasts were seen in
      macrophages in the leptomeningeal space, in monocytes circulating in
      leptomeningeal capillaries, or in the endothelial cells themselves, strengthening
      the hypothesis that monocytes and endothelial cells play key roles in the
      pathogenesis of cryptococcal meningitis. Similar fungal loads and cellular
      reactions were seen in mice and in 1 patient with acquired immune deficiency
      syndrome (AIDS), all with acute cryptococcal meningoencephalitis, and in mice and
      in 1 patient with AIDS, all with cured cryptococcal infection. Immunostaining
      revealed both the presence of cryptococcal polysaccharide in various brain cells
      and antigenic variability both from yeast cell to yeast cell and over time. Thus,
      our data established the relevance and interest that this experimental model has
      for investigation of the pathogenesis of human cryptococcal meningitis.

PMID- 12195381
TI  - Age-acquired immunity to a Plasmodium vivax invasion ligand, the duffy binding
      protein.
AB  - The interaction between the Plasmodium vivax merozoite Duffy binding protein
      region II (DBPII) and the human erythrocyte Duffy antigen leads to infection.
      Highly polymorphic regions of this protein may have arisen as a mechanism to
      avoid host immunity. To examine whether immunity to P. vivax is directed against
      these polymorphic regions of DBPII, age-associated changes in the frequency of
      specific DBPII alleles among 358 P. vivax-positive Papua New Guineans were
      examined. Although the overall number and diversity of DBPII haplotypes
      simultaneously infecting an individual decreased with increasing age, only
      certain alleles at particular loci declined in frequency, indicating preferential
      immune selection against these alleles. One such polymorphic locus formed part of
      a B cell epitope, and antibodies from exposed individuals differentially
      recognized alleles at this locus. Therefore, acquisition of strain-specific age
      acquired immunity is partially directed against polymorphic motifs within P.
      vivax DBPII, suggesting that these polymorphisms are maintained and likely arose
      under immune pressure in the host.

PMID- 12195382
TI  - Impact of microscopy error on estimates of protective efficacy in malaria
      prevention trials.
AB  - Microscopy is an imperfect reference standard used for malaria diagnosis in
      clinical trials. The purpose of this study was to provide an assessment of the
      accuracy of basic microscopy, to compare polymerase chain reaction (PCR)-based
      diagnosis with microscopy results, and to assess the effect of microscopy error
      on apparent protective efficacy. The sensitivity and specificity of basic,
      compared with expert, microscopy was determined to be 91% and 71%, respectively.
      In a clinical trial, agreement between PCR and microscopy results improved with
      expert confirmation of initial results. In a simulated 12-week trial with weekly
      routine malaria smears, a very high specificity (>99%) for each malaria smear was
      found to be necessary for an estimate of protective efficacy to be within 10%-25%
      of the true value, but sensitivity had little effect on this estimate. Microscopy
      error occurs and can affect clinical trial results.

PMID- 12195383
TI  - Innate and acquired resistance to amebiasis in bangladeshi children.
AB  - Entamoeba histolytica infection and colitis occurred in 55% and 4%, respectively,
      of a cohort of Bangladeshi preschool children observed for 2 years. DNA typing
      demonstrated that infecting E. histolytica isolates were genetically diverse.
      Innate resistance to infection in children was linked to the absence of serum
      anti-trophozoite IgG. Most children who lacked serum anti-trophozoite IgG failed
      to develop it in response to a new infection. The serum anti-trophozoite IgG
      response clustered in families, which is consistent with genetic inheritance.
      Acquired resistance to infection was linked to intestinal IgA against the
      carbohydrate-recognition domain of the E. histolytica galactose N-acetyl-d
      galactosamine lectin. This was associated with an 86% reduction in new infection
      over 1 year. Amebiasis is a common and potentially serious infection in children
      from Dhaka, and both innate and acquired immune responses limit infection.

PMID- 12195384
TI  - Diagnosis and outcome of preconceptional and periconceptional primary human
      cytomegalovirus infections.
AB  - Primary human cytomegalovirus (HCMV) infection occurring in pregnant women within
      3 months before (preconceptional) or within 4 weeks after (periconceptional) the
      last menstrual period represents an as-yet-undefined risk to the fetus. One
      (9.1%) of 11 newborns born to 12 women with preconceptional infection was
      subclinically infected (1 aborted fetus was not examined for infection). Of 20
      pregnancies in women with periconceptional infection, 7 were terminated before 12
      weeks of gestation (aborted fetus was not examined), 1 was terminated at 23 weeks
      after prenatal diagnosis of congenital infection, and 12 continued to term. Of
      those 12, 3 resulted in newborns who were congenitally infected. Thus, in the
      periconceptional group, intrauterine transmission occurred in 4 (30.8%) of 13
      pregnancies for which the virologic outcome was known. One newborn was
      symptomatic at birth, and disseminated HCMV infection was diagnosed in an aborted
      fetus. Periconceptional primary HCMV infection seems to bear a higher risk of
      unfavorable outcome than preconceptional infection, and counseling should be
      adjusted accordingly.

PMID- 12195385
TI  - Double-stranded RNA viral infection of Trichomonas vaginalis infecting patients
      attending a sexually transmitted diseases clinic.
AB  - Trichomonas vaginalis (TV) can be infected with double-stranded RNA (dsRNA)
      viruses that may have important implications for trichomonal virulence and
      disease pathogenesis. A cross-sectional study was conducted in a sexually
      transmitted diseases clinic to determine the prevalence and clinical significance
      of dsRNA viral infection of TV infecting men and women. Overall, dsRNA virus was
      present in 21 (75%) of 28 TV isolates (95% confidence interval [CI], 55%-89%).
      dsRNA viral infection of TV was not associated with the presence of discharge,
      dysuria, genital pruritus, or genital irritation or odor. However, patients with
      virus-positive isolates were significantly older than patients with virus
      negative isolates (median age, 38 vs. 23 years; P=.003), and virus-positive
      isolates were more prevalent among women (19 [86%] of 22 isolates; 95% CI, 65%
      97%) than among men (2 [33%] of 6 isolates; P=.02). The age and sex specificity
      of virus-positive isolates may aid in understanding the differences in chronicity
      and clinical presentation of TV in men and women.

PMID- 12195386
TI  - Pneumolysin activates the synthesis and release of interleukin-8 by human
      neutrophils in vitro.
AB  - The effects that the Streptococcus pneumoniae-derived, proinflammatory toxin,
      pneumolysin (8.37 and 41.75 ng/mL), has on the production of interleukin (IL)-8
      and tumor-necrosis factor (TNF)-alpha by human neutrophils have been investigated
      in vitro. Total and extracellular IL-8 and TNF-alpha were assayed by enzyme
      linked immunosorbent assay, and flow cytometry and colorimetric procedures were
      used to detect intracellular cytokine and cytokine messenger RNA, respectively.
      Treatment of neutrophils with pneumolysin either alone or in combination with the
      chemotactic tripeptide, N-formyl-l-methionyl-l-leucyl-l-phenylalanine (1 microM),
      resulted in a time-dependent (maximal at 6 h) increase in synthesis and release
      of IL-8 but not of TNF-alpha, which was associated with increased expression of
      IL-8 messenger RNA transcripts and was abrogated by either cycloheximide (10
      microg/mL) or depletion of Ca(2+) from the cell-suspending medium. These
      interactions between the toxin and neutrophils may contribute to the exaggerated
      pulmonary inflammatory responses caused by pneumolysin-producing strains of the
      pneumococcus.

PMID- 12195387
TI  - Escherichia coli O157 fails to induce a long-lasting lipopolysaccharide-specific,
      measurable humoral immune response in children with hemolytic-uremic syndrome.
AB  - Escherichia coli O157 lipopolysaccharide (LPS)-specific antibodies were measured
      in sequential serum samples from 131 children with serologically defined E. coli
      O157-associated hemolytic-uremic syndrome (HUS), using an enzyme immunoassay. On
      the basis of evaluation of 66 children with culture-proven E. coli O157 infection
      and serum samples from 132 age-matched control subjects, the assay showed a
      sensitivity of 95%, 88%, and 74% and a specificity of 99%, 99%, and 98% for IgM,
      IgA, and IgG, respectively. Anti-O157 LPS antibodies decreased below the cut-off
      levels in >50% of the children at 11 (IgM), 5 (IgA), and 11 weeks (IgG) after
      onset of diarrhea and 10, 4, and 10 weeks, respectively, after the onset of HUS.
      Children with enteropathic HUS fail to develop a long-lasting humoral immune
      response to the O157 antigen. Incomplete immunity to E. coli O157 may signal a
      risk for recurrent infections and has implications for serodiagnostic studies.

PMID- 12195388
TI  - Toll-like receptor 4 is not involved in host defense against pulmonary Legionella
      pneumophila infection in a mouse model.
AB  - Legionella pneumophila is a gram-negative microorganism that causes a severe
      pneumonia known as "legionnaires disease." Toll-like receptor 4 (TLR4) transduces
      the lipopolysaccharide signal and is therefore considered to play a role in host
      defense against gram-negative bacterial infection. To determine the role of TLR4
      in L. pneumophila pneumonia, C3H/HeJ mice, which display a nonfunctional gene
      encoding TLR4 (TLR4), and wild-type (wt) C3H/HeN mice were intranasally
      inoculated with L. pneumophila serogroup 1. Infection proceeded in an identical
      way in TLR4 mutant and wt mice, as reflected by similar bacterial outgrowth in
      the lungs. In addition, the inflammatory responses to L. pneumophila infection-as
      assessed by histopathologic analysis, cell influx in bronchoalveolar lavage
      fluid, myeloperoxidase activity in lungs, and lung cytokine concentrations-were
      indistinguishable in TLR4 mutant and wt mice. These data suggest that, in this
      mouse model, TLR4 does not play a role in resistance to L. pneumophila.

PMID- 12195389
TI  - Development of a murine model of cerebral aspergillosis.
AB  - Central nervous system (CNS) Aspergillus infection has a mortality rate in humans
      that approaches 95%. Because no animal models are available for studying this
      infection, we sought to develop a murine model of CNS aspergillosis. Inconsistent
      data were obtained for nonimmunosuppressed CD-1, C57BL/6, and DBA/2N mice after
      infection by midline intracranial injection of Aspergillus fumigatus. CD-1 mice
      given cyclophosphamide to produce immunosuppression had continuous pancytopenia.
      Dose-finding studies in CD-1 mice showed that infection with 5 x 106
      conidia/mouse consistently caused 100% mortality by day 5-8; no mice died before
      day 3. Histologic examination of samples of brain tissue showed focal abscesses
      containing Aspergillus hyphae. Fungus burdens in brain were higher than those in
      other organs, although Aspergillus disseminated to the kidneys and the spleen.
      The model we established provides an opportunity to study immune responses to and
      therapeutic options for CNS disease in an immunologically defined, genetically
      manipulable, and inexpensive species.

PMID- 12195390
TI  - Significant association of longer forms of CCTTT Microsatellite repeat in the
      inducible nitric oxide synthase promoter with severe malaria in Thailand.
AB  - A CCTTT microsatellite repeat in the inducible nitric oxide synthase (iNOS)
      promoter was analyzed among 256 adult patients with severe Plasmodium falciparum
      malaria and 179 adult patients with mild malaria living in northwestern Thailand.
      Genotypes with longer forms of the CCTTT repeat (alleles of > or =15 repeats)
      were significantly associated with severe malaria (odds ratio [OR], 2.14;
      P=.0029, chi(2) test). More interestingly, the summed repeat number of both
      microsatellite alleles in an individual was found to be a significant risk factor
      for severe malaria (OR, 1.11; logistic regression analysis, P=.0041). The single
      nucleotide substitution, -954G-->C, in the iNOS promoter was rare in Thai
      patients with malaria. No variations were detected in the iNOS promoter region
      containing functional NF-kappaB elements at -5.2, -5.5, -5.8, and -6.1 kb
      upstream of the iNOS transcriptional start site. Thus, a CCTTT repeat in the iNOS
      promoter may play a key role in the pathogenesis of severe malaria.

PMID- 12195391
TI  - Verocytotoxigenic Escherichia coli serologic responses in patients with hemolytic
      uremic syndrome.

PMID- 12195393
TI  - [The sixth Framework Programme of the European Community for research activities
      and role of the Italian Community].
AB  - The sixth Framework Programme of the European Community for research activities
      is founded on two new elements, which are essential for the realisation of the
      European Research Area. They are the Networks of Excellence and the Integrated
      Projects. The Italian Government has recently approved the new Guidelines for the
      scientific and technological policy. They are based on four Axes, which involve
      basic and applied research for a total funding of 14.175 million euro in three
      years. If this Programme is carried out, the Italian Research Community will
      further improve, both qualitatively and quantitatively, its scientific
      productivity. It should be pointed out that, in a recent review, the Institute
      for Scientific Information included Italy at 7th place in the international
      classification of medical research.

PMID- 12195394
TI  - [Microalbuminuria in nondiabetic adults].
AB  - This paper deals with the clinical relevance of moderate increase in urinary
      albumin excretion, commonly known as microalbuminuria, in non-diabetic adults.
      Presently there are several definitions of microalbuminuria. When measuring
      excretion rates, microalbuminuria is defined by thresholds of 30 mg/day or 20
      g/min with urine collections shorter than 24 hours whereas macroalbuminuria is
      defined by rates higher than 300 mg/day or micro 200 g/min, respectively.
      Clinical and epidemiological data indicate the presence of a correlation between
      blood pressure and microalbuminuria. Microalbuminuria is progressively more
      frequent with higher blood pressure (systolic or diastolic) also in non
      hypertensive persons. Antihypertensive drugs lower urinary albumin excretion, the
      effect is modest or absent for dihydropyridinic calcium-channel blockers, strong
      for inhibitors of the renin-angiotensin system. In addition to blood pressure,
      other factors directly related to urinary excretion of albumin are cigarette
      smoking, blood lipids, body mass and dietary protein. In non-diabetics,
      microalbuminuria anticipates lethal and non-lethal cardiovascular events. This
      correlation can also be observed in the range of urinary albumin excretion below
      the thresholds that define microalbuminuria. Present data are not consistent on
      the possible correlation between microalbuminuria and renal function in non
      diabetics.

PMID- 12195395
TI  - [Progression of chronic renal failure in remnant rats: role of arginase
      inhibition].
AB  - BACKGROUND: Oral administration of arginine to remnant (REM) rats (5/6 nx) slows
      the progression of chronic renal failure through a nitric-oxide(NO)-dependent
      mechanism. We have recently shown that inhibition of arginase, the main metabolic
      pathway of arginine, was able to induce similar results on renal dynamics (GIN:
      2001, 18:285-290). Aim of the present study was to test whether these changes
      were mediated by increased availability of arginine-derived NO. Methods. Three
      Groups of REM rats were studied for 8 weeks after surgery: 1) untreated REM
      (Group REM); 2) REM rats treated with arginine (1%) in tap water (Group ARG); 3)
      REM rats administered a Mn++-free diet, to induce partial inhibition of arginase
      (Group MNF). Normal unmanipulated rats were used as controls (Group NOR).
      RESULTS: Liver arginase activity was significantly depressed only in MNF-rats (
      35% vs. REM, p < 0.01). Blood pressure was significantly lower in Group MNF vs.
      ARG and REM after 6 weeks (p < 0.05). Proteinuria was significantly decreased in
      Group ARG (-42%, p < 0.05 vs. REM) and even more in Group MNF (-57%, p < 0.01).
      ARG plasma levels, decreased in REM rats (-41% vs. Group CON), were normalized in
      Group ARG (p < 0.01 vs. Group REM); arginase inhibition was able to increase such
      levels in Group MNF (+38% vs. REM) and this resulted in a proportional rise in
      urinary nitrite excretion (+33% vs. REM), grossly depressed in REM rats. Renal
      arginase activity was lower in all the Groups of remnant rats vs. Group NOR, but
      intrarenal concentrations of ARG were significantly lower only in rats of Group
      MNF (p < 0.05 vs. all the other Groups). Histological examination showed that MNF
      rats had a glomerular sclerosis index lower than in the other Groups (p < 0.05
      vs. Group REM and ARG). CONCLUSIONS: In conclusion, inhibition of arginase in
      remnant rats slows the progression of CRF and preserves renal histology through a
      direct and/or indirect NO-dependent mechanism.

PMID- 12195396
TI  - [Thalassaemia minor: national survey of uraemic patients under substitutive
      treatment].
AB  - BACKGROUND: The incidence of thalassaemia minor in end-stage renal disease
      patients is similar to that of the general population. Both these conditions are
      characterized by anaemia, but the underlying pathophysiology is quite different.
      Current literature lacks an adequate clinical survey of haemodialysis patients
      with thalassaemia minor. METHODS: The prevalence of thalassaemia minor (thal-m)
      in haemodialysis patients was assessed by a national survey collecting general
      information as well as clinical and haematological parameters. Data were also
      collected on the use of recombinant erythropoietin in these subjects. A dedicated
      questionnaire was sent to all Italian dialysis units. RESULTS: Only 116/705
      dialysis units returned the questionnaire (16.4%): 33 units did not have any
      patients affected by thalassaemia minor. No response was obtained from six
      Italian regions whereas ten regions returned only partial answers. The response
      from four regions was satisfactory (20%) while the completed questionnaire was
      returned by all units in only two small regions. A total of 7731 ESRD patients
      were collected, 240 (3.1%) were also affected by thal-m, 142 males and 98
      females. In the four regions with the highest response rates, Calabria 45%,
      Puglia 65%, Basilicata and Molise 100%, the prevalence of thal-m were 3.68%,
      4.56%, 3.3% and 1%, respectively. A total of 3623 uraemic patients (47% of all
      enrolled subjects) were collected from these four regions. Here is the patient
      geographic distribution: northern Italy 2.16% (response rate of 9.44%); central
      Italy 1.69% (response rate of 7.64%), southern Italy 3.77% (response rate of
      29.46%). The age range of thal-m patients was 17 to 90 years, the time spent on
      dialysis was between 3 and 384 months, the body weight was between 35 and 93 kg,
      the Hb value was between 6.2 and 13.6 g/dl, and the Htc value was between 19 and
      44%. A total of 230 thal-m patients were on haemodialysis while 10 patients were
      on peritoneal dialysis (4.2%). The mean haemoglobin level for the thal-m group
      was 9.8+/-1.4 g/dl and for the control group the value was 11.4+/-1.4 g/dl (p <
      0.0001). The use of rhEPO was on the average 7659+/-6256 u/wk for the thal-m and
      4378+/-4435 u/wk for the control group (p < 0.0001). The bodyweight was 129+/-105
      u/kg/wk (range 0-370). Finally, 17.9% of the thal-m patient did not use rhEPO,
      their Hb value was 10.66+/-1.67 g/dl (range 8.2-13). No patient went over 30
      thousand units and only 4 had such dosage in therapy. The 12.1% thal-m patients
      with Hb < 10 g/dl did not use rhEPO. The need for rhEPO per gram of Hb was 796+/
      722 u/wk in thal-m patients and 416+/-449 U/wk in control patients (p < 0.0001).
      Uraemic anaemia was corrected with 4.8 million red blood cells in the control
      group and with about 7.7 million red blood cells in the thal-m group.
      CONCLUSIONS: Data from this national survey, although incomplete, show that
      rHuEpo is less effective in these patients and its use does not seems to be
      correct. It is important to emphasise that recent Guidelines do not recommend
      neither a specific treatment for these patients nor the use of r-HuEpo. However,
      it should also be underscored that most thal-m patients do not reach the target
      Hb level suggested by the National Guidelines for the general population in
      chronic dialysis.

PMID- 12195397
TI  - [Natural history of hepatitis B virus infection in dialysis patients: prospective
      study by quantitative analysis of HBV viremia].
AB  - BACKGROUND: The natural history of hepatitis B virus (HBV) infection in patients
      undergoing maintenance dialysis is still unclear. The aim of this study was to
      measure the HBV viral load (HBV DNA) in a cohort (n=20) of HBsAg positive chronic
      dialysis patients over a 12-month observation period. METHODS; HBV DNA was
      measured by the Amplicor HBV MonitorTM Test Kit, an in vitro test that utilizes
      Polymerase Chain Reaction (PCR) nucleic acid amplification and DNA hybridisation
      for the quantitative measurement of hepatitis B viral DNA in human serum.
      Amplicor HBV MonitorTM Test Kit amplifies a sequence in the pre-Core/Core region
      of the HBV genome with biotinylated and non-biotinylated oligonucleotide primers.
      RESULTS: There was no significant difference between the median HBV load at the
      start and the end of the study, 1.85 x 104 HBV copies/ml (percentile 16.84; 6.35
      x 102 - 3.5 x 106 HBV copies/ ml) and 8.5 x 103 HBV copies/ml (percentile 16.84;
      5.5 x 102 - 6.38 x 105 HBV copies/ml), respectively. These serum HBV DNA levels
      were lower than those measured by the same test in patients with chronic
      hepatitis B and normal renal function (Hepatology 2000; 32: 116-23). In the group
      of HBsAg positive carriers on dialysis, we identified three patterns of HBV
      viremia over time: 1) patients (n=6) with persistent HBV DNA, 2) those (n=2) with
      undetectable HBV DNA and 3) those (n=12) with intermittent HBV DNA. Patients with
      persistent HBV DNA (median, 3.3 x 104 HBV copies/ml; percentile 16.84; 3.5 x 103 
      2.3 x 106 HBV copies/ml) had higher viral HBV load than those with intermittent
      HBV viremia (median, 1.2 x 103 HBV copies/ml; percentile 16.84; 3.5 x 102 - 2.3 x
      104 HBV copies/ml) (p=0.0001). Patients with persistent HBV DNA had higher
      frequency of serum hepatitis B e antigen (HBeAg) positivity than those showing
      intermittent and negative HBV DNA, 50% (3/6) vs. 0% (p=0.04). The frequency of
      serum IgM antibody against hepatitis B core antigen (IgM anti-HBc) was higher in
      patients with persistent HBV DNA than those having intermittent or negative HBV
      DNA, 100% (6/6) vs. 33% (4/12), p=0.03. We detected no difference in
      aminotransferase activity between patients with persistent HBV DNA and those
      showing intermittent or negative HBV DNA. In the group with persistent HBV DNA,
      the mean difference between maximum and minimum values of HBV DNA observed in
      each individual patient was 6.13+/-1.25 decimal logarithm (Log10) and in patients
      with intermittent HBV DNA 3.87+/-1.49 Log10 (p=0.006). In the entire group, the
      fluctuations in HBV DNA values over time between and within individuals were not
      significant. CONCLUSIONS: The viremic HBV load was low and relatively stable over
      a 12-month follow-up period; three patterns of HBV viremia over time were
      observed; 30% of the viremic patients had persistent HBV viremia, and those
      patients had larger viral load and higher frequency of HBeAg and anti-HBc IgM
      than did patients with intermittent or negative HBV DNA. Prospective studies with
      longer observation periods are in progress to fully understand the natural
      history of HBV in these immunosuppressed patients.

PMID- 12195399
TI  - [Costs of dialysis in hospitalised patients with acute or chronic renal failure,
      according to area of treatment].
AB  - BACKGROUND: In Italy, dialysis reimbursement is regulated by the "Tariffario
      delle prestazioni ambulatoriali" (G.U. N  216, 14/9/1996), which does not take
      into account separately the dialysis sessions performed in hospitalised patients.
      In these cases the dialysis activity is considered within the final DRG
      (Diagnosis Related Group). Aim of the study was an analysis of production costs
      of dialysis performed in hospitalised patients, according to the setting in which
      dialysis is performed (Intensive Care Units (ICUs), other Units, hospital
      dialysis ward). METHODS: The direct production costs were assessed by the "bottom
      up" technique logic (cost definition from the single elements needed for
      producing the treatment) referring to specific Cost Centres. The main items
      considered were health-care staff, dialysis supplies and hardware, blood tests,
      dialysis data recording and transmission. RESULTS: During the year 2000, there
      were 4,450 treatments performed in 490 patients. They included 924 haemodialyses
      in ICUs; 2,531 in the nephrology hospital dialysis ward; 602 peritoneal dialysis
      treatments in ICUs-other wards, 393 in the nephrology ward. Direct cost per
      haemodialysis treatment ranged from 276.05 E (UF) to 413.46 E (HF) in ICU, from
      170.47 E (Bicarbonate Haemodialysis) to 275.36 E (Slow Haemofiltration) in
      hospital dialysis ward; for peritoneal dialysis between 128.95 E (CAPD in
      dialysis ward) and 282.10 E (CAPD in ICU/other Units). During the year 2000, the
      global cost of production was 1,038,346.65 E. CONCLUSIONS: The cost of dialysis
      in hospitalised patients is high. A dedicated budget is needed to avoid deficits,
      particularly in highly specialised Units of large referral hospitals.

PMID- 12195398
TI  - [Intravenous folinic acid and vitamin B12 supplementation and homocysteine
      concentration in hemodialysis patients].
AB  - INTRODUCTION: Hyperhomocysteinemia is one of the causes of the increased
      incidence of cardiovascular disease in uremia. Since homocysteine (Hcy)
      metabolism depends on the availability of folate and vitamin B12, we have
      measured the effects of chronic i.v. supplementation of folinic acid and vitamin
      B12 in a group of patients on maintenance hemodialysis. METHODS: We compared the
      blood concentration of total Hcy (tHcy), vitamin B12 and folate and the
      intraerythrocyte concentration of folate in a group of 27 hemodialysis patients
      (Treated group), given an i.v supplementation with folinic acid (0.9 mg) and
      Vitamin B12 (cyanocobalamine 1.5 mg and hydroxycobalamine 1.5 mg) three times per
      week at the end of each dialysis session with those measured in a similar group
      of 28 hemodialysis patients without supplementation (No Treatment group). The
      patients were also characterized for the thermolabile variant (mutation C667-->T)
      of the enzyme methylene-tetrahydrofolate reductase (tMTHFR). RESULTS: High plasma
      levels (< 11.7 micromol/L) of tHcy were observed in 54/55 patients. T patients
      had Hcy values significantly lower than NT ones (31.7+/-3.6 vs. 1.1+/
      8.3micromol/L, p < 0.05). Serum vitamin B12 (1200 73.6 vs. 762+/-72.2 pmol/L, p <
      0.001) and intraerythrocyte folate levels were also significantly higher in the T
      group (2176+/-127 vs. 1511+/-156, p < 0.005), while no significant difference was
      observed for serum folate. The distribution of tMTHFR genotypes was similar in
      the two groups. Homozygous patients showed higher levels of Hcy in comparison
      with wild type patients both in the whole population (62.32+/-15.9 vs.30.43+/
      3.2, p < 0.05) and in the NT group (87.8+/-25.3 vs.36.8+/-13.1., p < 0.05), while
      no significant difference was observed among genotypes in the T group.
      CONCLUSIONS: Uremic patients on hemodialysis, when supplemented with even low
      i.v. dose of folinic acid and vitamin B12, show significantly lower plasma levels
      of tHcy than non-supplemented patients.

PMID- 12195400
TI  - [Herpetic viruses and renal transplantation].
AB  - Over the last few years emerging evidence indicate the involvement of herpes
      viruses in the pathogenesis of several medical complications in transplanted
      patients. Herpes viruses are transmitted via inter-human contact and cause a
      primary infection, which commonly fails to give clinical signs and may persist
      even for years in a latent state in healthy subjects. In transplanted patients,
      herpes viruses may be transmitted through the transplanted organ or may be
      reactivated because of the use of powerful immunosuppressive drugs. Moreover, the
      persistence of immunosuppression greatly favours the clinical expression and
      severity of virus infection. Thus, herpes viruses seem to be involved in both
      acute and chronic deterioration of graft function, in the pathogenesis of post
      transplant lymphoproliferative disorders and Kaposi sarcoma, and even in vessel
      atherosclerosis. This review will focus on relevant clinical aspects of herpes
      virus infection, namely cytomegalovirus, EBV, herpes simplex 1 and 2, varicella
      zoster virus, HHV-6, HHV-7 and HHV-8, in kidney transplanted patients.

PMID- 12195401
TI  - [Coronary angiography in uraemic patients awaiting kidney transplantation].
AB  - BACKGROUND: Cardiovascular disease is the leading cause of morbidity and
      mortality in uraemia. Coronary angiography (CA) in patients awaiting kidney
      transplantation (PAKT) is still a matter of debate. In order to evaluate
      atherosclerotic coronary damage in PAKT, CAs of 12 PAKT were matched with those
      of 13 dialysis patients (P) affected by ischaemic heart disease IHD. METHODS: Age
      sex, length of time on renal replacement therapy, diabetes, smoking and
      hyperphosphataemia history, clinical diagnosis of IHD, cerebrovascular (CV) and
      peripheral vascular (PV) disease, mean blood pressure (BP), cholesterol,
      triglycerides, calcium, phosphate, albumin, haemoglobin, haematocrit and weekly
      dose of erythropoietin (EPO-dose) were derived from clinical records. RESULTS:
      PAKT were younger (48 9 vs 63 9 years, p < 0.01) and had higher diastolic BP
      values (86+/-10 vs 79+/-4 mmHg, p < 0.05) than IHD P. On the contrary all the
      other parameters investigated were not different in the two groups of P.
      Prevalence of IHD in PAKT was 16% while frequency of CV and VP disease were not
      different in the two groups. In 9 of IHD P stenotic lesions >/=75% of normal
      reference segment were diagnosed in 3 or more vessels whilst in PAKT there were
      atherosclerotic lesions in right coronary artery, left anterior descending artery
      and left circumflex artery in 41, 66 and 33% respectively. Narrowing percentage
      of the coronaries in PAKT and IHD P were: right coronary artery 27+/-42 vs 75+/
      35, p < 0.05, left anterior descending artery 29+/-25 vs 86+/-15, p < 0.001, left
      circumflex artery 11 16 vs 47+/-38, p < 0.05 respectively. CONCLUSIONS: Our study
      shows that atherosclerotic coronary damage is present in PAKT and, although not
      hemodynamically significant, it could be an important risk factor for clinical
      expression of IHD. We conclude that CA should be performed in PAKT especially in
      those over 45 years.

PMID- 12195402
TI  - [Historical Archives of Italian Nephrology: Scientific ideas and projects carried
      out by the history of medicine and nephrology].
AB  - Some recent historical celebrations of modern Italian nephrology offer the
      opportunity to write about the meaning of the history of medicine and nephrology.
      First of all, the question "what do we learn from history" is wrongly phrased. It
      is from trying to learn about history, from the effort required to achieve a
      historical and epistemological perspective, that we may learn how people as
      individuals or as a group solved the problems of meeting their common human
      needs. Medicine is itself an eminently historical endeavour. There is history in
      medicine as well as history of medicine. According to Paracelsus, the history of
      medicine is medical science and medical science is essential history in the
      widest sense of the word. The word "history" embraces the concepts of human
      nature, the world in which human nature is revealed and the thoughts guiding it
      through life. If the history of medicine and nephrology is observed in all
      aspects of their evolution, we can see how it had a beneficial role on the work
      of physicians by reminding them that, prior to the light of achievement, the
      discovery of all medical principles is preceded by errors and doubts. We report
      on nephrological debates, controversies and achievements and we call attention to
      the need to focus on the present through the involvement of medical historians in
      the analysis of contemporary health policy issues and clinical methodology.

PMID- 12195403
TI  - [Borderline indications for renal biopsy].
AB  - The Authors report 3 cases with clinical renal manifestations where the
      indication to perform a renal biopsy was defined as borderline. The uncertain
      indication was related to the clinical presentation, with a pattern of urinary
      abnormalities, such as isolated microscopic hematuria, microscopic hematuria
      associated with mild proteinuria, and isolated proteinuria. In addition, similar
      questions on biopsy are raised for chronic renal failure and elderly patients. In
      the literature, microscopic hematuria without significant proteinuria shows that
      25% of adult patients have no histological abnormalities. A higher percentage is
      found among children. The other cases exhibit a pattern of IgA nephropathy,
      Alport's syndrome, thin BM nephropathy and arteriolar C3 deposition. The
      percentage of an abnormal histological picture increases if the patients have a
      family history of hematuria, and if there are concomitant episodes of macroscopic
      hematuria, because of an increase in IgA nephropathy and Alport's syndrome,
      respectively. In the last cases, therefore the indication to perform a renal
      biopsy increases. For those patients without these characteristics, a renal
      biopsy can be delayed whereas in cases of microscopic hematuria with proteinuria
      or isolated proteinuria the indication for a renal biopsy is stronger, because
      the spectrum of glomerulopathies is wider, and the possible evolution to renal
      failure after 10 years is higher (10-14% of cases). In patients with chronic
      renal failure the biopsy is contraindicated for cases where the thickness of the
      cortical section of the kidney is lower than 8-10 mm, because of possible
      technical difficulties, lower diagnostic information due to sclerosis and higher
      risk of complications. The prolonged bleeding time and the consequent risk of
      bleeding can be avoided by i.v. infusion of vasopressin 2 hours prior to biopsy.
      The higher indications are for those patients who may be susceptible to a medical
      treatment, capable to slowing down the progression of nephropathy. Finally, in
      elderly patients the biopsy is indicated in almost all cases because of the
      recently confirmed high incidence of glomerulopathies. In the aged there is a
      higher frequency of membranous GN, crescentic-ANCA associated GN, amyloidosis
      and, according to some Authors, post-infectious GN. In all cases a precise
      histological diagnosis can correct an erroneous diagnosis made according to
      clinical data alone. In the elderly the indication for biopsy aims at making an
      exact diagnosis of nephropathy, especially for acute renal failure: for this
      purpose age itself should not become an obstacle.

PMID- 12195404
TI  - [One hundred years old and under haemodialysis treatment for 5 years...a case to
      ponder].
AB  - BACKGROUND: The average age of the patients, introduced in the dialytic
      programme, is progressively increasing in relation to the prolonging of life and
      to the technological progresses. All this places the nephrologist to ask himself
      if the age has to be considered a limiting factor for the introduction of a
      patient in the dialytic programme. CASE REPORT: We report on a patient who
      started her dialytic programme when she was 95. After 5 years, at the age of 100,
      she uneventfully completed 60 months of haemodialytic treatment. Right from the
      start we decided to use as vascular access a double Tesio catheter, which was
      never replaced because it was the most appropriate for the patient's age. During
      the follow-up period the patient was not hospitalised and her clinical condition
      was satisfactory. DISCUSSION: According to the latest epidemiological and
      clinical data, this case emphasises the concept that it would be wrong to refuse
      the haemodialytic treatment to such patients only because of their frailty.
      Moreover, the lack of either univocal prognostic indications, based on scientific
      criteria, or special national laws confirm that the decision to treat the patient
      depends exclusively on the physician's ethical and professional background as
      well as the patient's autonomy and conscience.

PMID- 12195405
TI  - [Syndrome of inappropriate ADH secretion: a late complication of hemopoietic stem
      cell allograft].
AB  - An 11-year old boy with acute lymphoid leukemia underwent umbilical cord stem
      cell infusion. This was followed at day 15 by the onset of asymptomatic hypotonic
      isovolemic hyponatremia. The disorder could be attributed to a syndrome of
      inappropriate ADH secretion (SIADH), most probably related to the massive i.v.
      induction treatment with cyclophosphamide. The major causes and clinical variants
      of SIADH are reviewed, with particular emphasis on the complications of
      chemotherapy in hematological diseases. Worsening of hyponatremia during routine
      parenteral feeding, as opposed to normalization of plasma Na+ by infusion of
      hypertonic saline, emphasize the importance of early accurate diagnosis and
      careful follow-up of these iatrogenic sequelae of stem cell allograft.

PMID- 12195406
TI  - [Rate of urinary anomalies in school children from a rural community in the
      Italian region of Puglia].

PMID- 12195407
TI  - [Effect of magnesium on parathormone levels in kidney transplant patients].

PMID- 12195408
TI  - [The Socisin Mailing List: assessment at 12 months].
AB  - BACKGROUND: This Mailing List (ML) is an automatic e-mail distribution system on
      a specific topic. The medical world uses MLs to keep specialists in touch,
      however far apart they may be. The Socisin ML, circulated for discussion among
      members of the Italian Society of Nephrology (SIN), was one year old on 30th
      September 2001. This paper reports on its first 12 months in use. METHODS: We
      analysed all data on the number of messages received, accepted and rejected,
      their characteristics and authors, as well as the numbers subscribing and
      unsubscribing to the list. RESULTS: The number of messages were 391, 171 (43.7%)
      of them related to genuine scientific discussion. The proportional weight of the
      topics discussed was: peritoneal dialysis 51% (n=88), hemodialysis 40% (n=68),
      nephropathology 8% (n=13), transplantation 1% (n=2). Twenty-five congresses,
      symposiums and meetings were presented and one research trial was implemented
      after its presentation to the members. Compared with the Nephrology international
      ML, the number of messages were 13.5% (391/2907). Membership increased from 336
      to 443 (+32%). There were 124 new subscribers and 17 unsubscribers (+107). During
      this first year, 146 nephrologists sent at least one message to the ML.
      DISCUSSION: Our objective is to extend the number of participants, make the
      discussion increasingly scientific, and cover all aspects of nephrology. The
      Socisin ML will certainly become very valuable to Italian nephrologists provided
      it continues to grow and keeps to the rules pertinent to such tools and the
      spirit of a "common" project.

PMID- 12195409
TI  - [The essential of medical assistance and the rationalisation of the budgetary
      expediture].
AB  - The Italian Government has recently approved the basic healthcare levels that
      should regulate medical expenses. The Italian Regions shall monitor if drug
      prescriptions and healthcare in hospitals are appropriate and in line with the
      national guidelines prepared by The Agency for Regional Medical Services. It is
      essential to reduce medical assistance in the hospitals and intensify work and
      homecare programmes.

PMID- 12195410
TI  - [ANCA-associated vasculitis].
AB  - ANCA-associated vasculitis. The term "antineutrophil cytoplasm antibody (ANCA)-
      associated vasculitis" (AASV) ihighers generally used to include primary
      vasculitis syndromes in which circulating ANCA against proteinase 3 (PR3) and
      myeloperoxidase (MPO) are commonly found. AASV syndromes include Wegener's
      granulomatosis, microscopic polyangiitis, idiopathic pauci- immune necrotizing
      crescentic glomerulonephritis and Churg-Strauss syndrome (CSS). AASV syndromes
      share some general clinical-histological manifestations, such as rapidly
      progressive renal failure and focal necrotizing glomerulonephritis with
      extracapillary proliferation in the absence (or in the presence of modest)
      immunoglobulins deposits (pauci- immune). Untreated AASV follow a progressive
      course with a fatal outcome due to vital organ failure. The combination of
      cyclophosphamide and prednisone is now established as the treatment of choice for
      patients with AASV, but there is considerable debate over the duration of therapy
      and the best way to administer cyclophosphamide. Treatment of AASV can be divided
      into two phases: an induction of remission and a maintenance of remission phase.
      Patients with AASV and renal involvement (serum creatinine less than 500  ml/L or
      5.6 mg/dl) should be treated with a combination of oral prednisone with gradual
      tapering and cyclophosphamide. Once remission is achieved, usually after 3-6
      months, azathioprine should replace cyclophosphamide. It is not known for how
      long treatment should be continued but at least one year of treatment after
      remission is warranted. When serum creatinine is than 500  ml/L (5.6 mg/dl)
      and/or oliguria is present, the addition of methylprednisolone pulses and/or
      plasma exchange should be considered.

PMID- 12195411
TI  - [Increased in vitro and ex vivo proliferation of erythroid precursors induced by
      calcitriol in chronic renal failure. Synergistic effect with rHuEPO].
AB  - BACKGROUND: Calcitriol (C) improves anemia in chronic renal failure. This
      improvement may be related to the suppression of iPTH release, but also to a
      direct effect on erythropoiesis. MATERIALS AND METHODS: In order to verify this
      hypothesis, 33 patients with chronic renal failure were enrolled: 24 were
      undergoing hemodialysis, 9 managed conservatively. All patients were free from
      other chronic or hematological disease, had a negative DFO test and aluminum
      levels below 20 mcg/l. iPTH range was 250-480 pg/l. None had yet been treated
      with C. In vitro study- Samples were drawn for a basal erythroid precursors
      (Burst Forming Unit-Erythroid BFU-E) study. After mononuclear cells were isolated
      by centrifugation with Ficoll-Hypaque, they were incubated for 15 days with
      rHuEPO 3U/ml (A), rHuEPO 3U/l + C 30 pg (B), rHuEPO 3U/ml + C 300 pg (C), rHuEPO
      30 U/ml + C 300 pg (D) was performed. Ex vivo study- After the basal evaluation,
      10 pts on dialysis were treated with C (Calcijex-Abbott) 1  g three times a week.
      BFU-E studies were performed after 1,2 and 4 months. RESULTS: In vitro, culture B
      showed an increased BFU-E proliferation vs A (41+/- 23 vs 27+/-15, p less than
      0.02); in C and D cultures proliferation was 61+/-31 and 78+/- 42 respectively, p
      less than 0.01 vs A. There was no difference among pts with renal failure and pts
      treated conservatively. During the in vivo study all cultures showed a
      progressive proliferation increase, without a plateau level (basal, after 1, 2, 4
      months respectively): in A: 17+/-8, 22+/-13, 30.9+/-14.9, 41.4+/-20; in B: 27.3+/
      15, 35.6+/-20, 45.5+/-21, 57+/-26; in C: 48.2+/-20.6, 63.7+/-32, 75.7+/-37, 83+/
      40; in D: 72+/-24, 91+/-42, 106+/-42, 110+/-42.3 (always p less than 0.001). The
      hematocrit and hemoglobin increase was constant but not significant. The iPTH
      decrease was not related to BFU-E proliferation. CONCLUSIONS: In chronic uremia C
      has a direct effect on erythroid precursor proliferation, both in vitro and ex
      vivo, with a sinergystic effect with rHuEPO. This effect is not related to iPTH
      suppression. C may be a useful adjuvant therapy for rHuEPO treatment.

PMID- 12195412
TI  - [The need for integrated care of patients with chronic nephropathies: the
      epidemiology of 'late referral'].
AB  - BACKGROUND: The recent need for information has prompted this collaboration
      between health system epidemiologists (Basilicata) and clinicians to compare
      models of 'local' epidemiology in the management of diseases. The referral of
      patients to a nephrologist represents a working hypothesis of research-
      intervention. METHODS: Analysis of renal registry (RR) and administrative
      databases (hospital discharge abstracts/HDA, ambulatory);ad hoc surveys. RESULTS:
      Patients on dialysis between 1994 and 1998 are 594, cumulative deaths are 190
      (32%). Males and the elderly (age = 65 years) are associated with more than 50%
      and threefold increase in relative risk of death, and with a diabetic nephropathy
      of 60% vs other renal diseases. Of 570 patients alive in 1996, 442 are linked
      with 2,628 HAD. Comorbid conditions are underreported in the RR (the Charlson
      index has been computed using HDA). Of 66 new dialysis cases, 31 are referred to
      a nephrologist only 6 months before the start of dialysis (47%) (22% diabetics).
      Patients discharged with chronic nephropathies (CN) and diabetes are 21% of CN
      patients (5% of diabetics). Of 100 patients with pre-end stage renal disease and
      diabetes, only 11-14 are discharged from the nephrology ward. At the local level,
      3 out of 4 patients with serum creatinine higher than 1.5 mg/dl are not referred
      to a nephrologist. The prevalence of CN may vary from 0.4% to more than 1%.
      CONCLUSIONS: While an improvement in health databases in the regions is underway,
      collaboration studies are essential for planning specific interventions for
      prevention and management of diabetic nephropathy to improve the use of resources
      in nephrology.

PMID- 12195413
TI  - [Hepatopathy and hepatitis B virus infection in dialysis patients: cross
      sectional study].
AB  - BACKGROUND: Control of spread of HBV infection in dialysis units in developed
      countries has been one of the major advances in managing end-stage renal disease
      (ESRD). Patients with chronic HBV, however, continue to enter the population pool
      of dialysis patients and transplant candidates. The clinical significance related
      to the presence of HBsAg in serum of dialysis patients has not been completely
      understood. AIM AND METHODS: We collected demographic, biochemical and
      virological data from a large (n=464) population of patients on maintenance
      dialysis. This was done to assess the influence of virological and host factors
      on hepatocellular damage, as shown by serum aminotransferase activity. RESULTS:
      The frequency of HBsAg positivity in our dialysis population was 8.2 % (38/464);
      the rate of HBsAg positive patients showing HBe antigen was 20.6% (7/34). Twenty
      two (84.6%) of 26 HBsAg positive patients showed detectable HBV DNA in serum by
      Amplicor HBV MonitorTM Test. HBsAg positive patients had serum aminotransferase
      activity significantly higher than HBsAg negative individuals; GOT (AST) 25.1+/
      29.9 vs. 16+/-21.5 UI/L (p=0.001), and GPT (ALT) 31.3+/-52.5 vs. 17.7+/-21.9 UIL
      (p=0.034). In the subset of HBsAg positive dialysis patients, those in the
      replicative phase HBeAg positive) had aminotransferase activity higher than HBeAg
      negative individuals, AST, 42.3+/-43.6 vs. 22.4+/-27.3 UI/L (p=0.097) and ALT,
      49.41+/-54.7 vs. 29.17+/-55.76 UI/L (NS) respectively. We did a multivariate
      analysis by standard least square model on the entire patient group and we found
      independent and significant association between detectable HBsAg in serum and AST
      (p=0.0089)and ALT (p=0.0159) values. There was an independent and significant
      relationship between age and ALT (p=0.01). CONCLUSIONS: In our study group, HBsAg
      positive patients on dialysis had serum aminotransferase activity significantly
      higher than that measured in HBsAg negative individuals. However, mean
      transaminase levels in HBsAg positive patients on dialysis were below the upper
      limit of normal for the reference range of healthy controls. HBsAg positive
      dialysis patients with active viral replication showed the greatest liver damage.
      Studies are in progress to understand further HBV-related liver disease in
      dialysis population.

PMID- 12195414
TI  - [Dialytic therapy in severely burnt patients with acute renal failure].
AB  - BACKGROUND: Appearance of acute renal failure (ARF) in severely burnt patients
      (GU) is a serious complication. It has a negative prognostic value and almost
      always develops in the context of multiple organ dysfunction syndrome (MODS)
      induced by sepsis. Over the last 20 years, according to data available, the
      mortality rate has been reported to reach about 75%. We have analyzed the initial
      results obtained in GU patients who were admitted to the Intensive Care Unit of
      the Burns Center in Turin. METHODS: Out of 105 GU patients admitted between July
      1999 and September 2000 (burned surface area (BSA) 23.8%, range 2-95%, mortality
      rate 13.7%), 7 patients (6.4%) had complications of ARF requiring extracorporeal
      dialytic therapy (38 HF sessions lasting 4-6 hours, 2 HF + 12 HDF + 1 UF sessions
      lasting 8-11 hours). RESULTS: Total BSA of 7 GU patients with ARF was 62.5+/
      11.3% (mean +/-SEM). Mortality rate was 71.4% which was due to septic shock and
      MODS. ARF onset was at 28.4+/-8.4 days from admission. Dialytic treatment started
      at Crs 2.3+/-0.42 mg/dl, and patients were treated for 7.6+/-3.5 days with a
      weight loss of 1859+/-161 gr/die. Circuit anticoagulation was obtained by minimal
      amount of heparin (132.2+/-26.5 U/hour) and no hemorrhagic complications were
      observed. CONCLUSIONS: In GU patients with ARF the dialytic treatment with daily
      long-lasting convective- diffusive techniques permitted us to achieve a survival
      and dialytic adequacy similar to those reported with continuous renal replacement
      therapies; however, mortality rate is high and related to septic shock and MODS.

PMID- 12195416
TI  - [Kidney transplantation before starting dialysis therapy].
AB  - The rate of the clinical adoption of the so-called pre-emptive transplantation is
      widely different among countries. In North America it represents 25 % of the
      total living donor transplantations; in Norway and Sweden it is 15 % and 9 %,
      respectively, of all grafts performed; in Italy it is less than 1%, whilst in
      countries like Austria, Germany and Ireland pre-emptive transplantation is
      nonexistent. Some concern on this type of transplantation was raised in the
      Seventies and were mainly based on the evidence that uraemia has an
      immunosuppressive effect, which could be weaker in the pre-dialysis period.
      Several clinical observations in the pre- cyclosporin era supported this
      assumption. Starting from the Eighties, however, several studies have
      demonstrated that pre-emptive transplantation may yield better recipient and
      graft survival. Moreover, a recent retrospective study, based on higher than 8000
      living donor grafts that included both treated and untreated by long-term
      dialysis before transplantation, showed in the pre-emptive cohort a 52 %
      reduction in graft losses after the first year and also a lower incidence of
      acute rejections. Among the advantages of pre-emptive transplantation we find
      better rehabilitation and especially a lower risk of job loss. The risk of poorer
      patient compliance, as initially pointed out, has no longer been reported and can
      be overcome by adequate psychological preparation of the patient. Most centres
      performing pre-emptive transplantation favour the use of living donor because of
      the general shortage of cadaver kidney vs. the increasing number of dialysed
      patients on the waiting list. Nevertheless, in special circumstances (national
      programs with short waiting lists, uremic type I diabetics, children, primary
      type I hyperoxaluria), some AA also recommend the use of the cadaver donor.

PMID- 12195415
TI  - [Prevalence of malnutrition in uremic patients undergoing hemodialysis therapy in
      Puglia and Lucania].
AB  - BACKGROUND: Calorie-protein malnutrition is associated with increased morbidity
      and mortality in hemodialysis patients. The aim of this study was to evaluate the
      prevalence of malnutrition in uremic patients treated with hemodialysis in two
      areas of Southern Italy. METHODS: A questionnaire was sent out to all Dialysis
      Centers in the two regions to select and enrol eligible patients by considering
      these parameters: Body Mass Index (BMI), serum albumin, serum creatinine, urea,
      calcium, phosphate, triglycerides, cholesterol, body weight. Enrolment criteria
      were patients on dialysis for at least six months and BMI less than 21 kg/m2. The
      dialytic dose was evaluated by reporting the hours of dialysis and filter
      surfaces. The number of weekly sessions (n. 3) remained unchanged over time.
      RESULTS: Twenty-three Dialysis Centers in the two Regions replied to our
      questionnaire and 149 patients were enrolled in the study out of the 1546
      patients examined. The overall prevalence of calorie-protein malnutrition was
      observed in 9.6% of the patients. The prevalence of malnutrition was found to be
      higher in males and in patients on dialysis for longer time. We observed no
      correlation with the hypoproteic diet administered in the pre-dialysis phase.
      Malnourished patients showing progressive weight loss were older and had
      undergone dialysis for a longer time. CONCLUSIONS: This retrospective study
      indicates low prevalence of malnutrition in the two regions examined. The lack of
      correlation between the hypoproteic diet and dialytic dose suggests the need for
      further studies to evaluate if increased dialytic dose or early start of dialysis
      could improve the nutritional status and quality of life in elderly patients.

PMID- 12195417
TI  - [Bonferroni in biomedical research].
AB  - The statistical methods for multiple comparisons are described in the paper. The
      pros and cons of Bonferroni correction versus more recent methods such as Holm
      correction are outlined. The lack of scientific consensus on the methods to be
      used in the different areas of biomedical research is shown by the disagreements,
      often quite harsh, between different statisticians. The papers presented at the
      meeting held in September 2001 in memory of Carlo Emilio Bonferroni, Rector of
      the Istituto Superiore di Scienze Economiche e Commerciali di Bari from 1925 to
      1933 are summarized. In the meeting there was the historical reconstruction of
      the Bonferroni correction, from Boole (1850) to Olive Dunn (1959). In the meeting
      there was also a presentation concerning Bonferroni's ideas (he was a moderate
      frequentist) in the field of probability, appreciated even by a strong Bayesian
      such as de Finetti in his memorial talk given in 1961, one year after
      Bonferroni's death.

PMID- 12195418
TI  - [Hyperaldosteronism and simultaneous pheocromocytoma: a puzzle case].
AB  - Pheochromocytoma and primary hyperaldosteronism are well-known causes of
      hypertension. It was recently reported that their frequency in the hypertensive
      population is 0.1-0.2% and 3-15%, respectively. We describe the case study of a
      patient with severe hypertension (200/100 mmHg) and the coexistence of
      pheochromocytoma and primary hyperaldosteronism attributable to adrenal
      hyperplasia. The originality of this clinical report is that the patient
      presented a pheochromocytoma in the left adrenal gland and hyperplasia of the
      contralateral adrenal gland. The simultaneous presence of pheochromocytoma and
      primary hyperaldosteronism in the same patient is probably due to either genetic
      predisposition or to specific environmental risk factors for these adrenal
      diseases.

PMID- 12195419
TI  - [Case report: reversible acute renal failure following therapy with both
      ketorolac (non-selective non-steroidal anti-inflammatory drug NSAID) and
      celecoxib (COX-2 selective) in the same patient].
AB  - BACKGROUND: We present the case of acute renal failure complicating the course of
      therapy with both ketorolac (non-selective Non-Steroidal Anti-inflammatory Drug,
      NSAID), and celecoxib (COX-2 Selective Inhibitor) in an elderly woman with
      chronic liver disease, heart failure and chronic renal failure. The main effect
      of NSAIDs is the inhibition of cyclooxygenase (COX), the enzyme involved in
      prostaglandins synthesis. The nephrotoxicity of NSAIDs is linked to this effect
      since prostaglandins not only act in response to inflammatory stimuli, but also
      play a role as modulators of some physiological renal functions. Under conditions
      of reduced renal perfusion, acute renal failure secondary to NSAIDs use may occur
      if the vasoconstrictive forces stimulated to maintain the filtrating function are
      not balanced by prostaglandin-induced vasodilatation. About ten years ago, two
      COX isoforms were demonstrated: COX-1 whose products are involved in regulating
      physiological functions and COX-2 which is expressed by a number of inflammatory
      stimuli. The discovery of molecular differences between COX-1 and COX-2 allowed
      the development of pharmacological agents selectively inhibiting COX-1 or COX-2.
      Selective inhibitors of COX-2 are now available. However, COX-1 products are
      involved in inflammatory reactions, whereas COX-2 products play a physiological
      role in many tissues and organs, including the kidney. These observations raised
      many doubts regarding the renal safety of COX-2 Inhibitors before they became
      commercially available. These doubts have been recently confirmed in the
      Literature. CONCLUSIONS: The case we report seems to confirm that, in patients at
      risk, the renal adverse effects of non-selective NSAIDs and of COX-2 Inhibitors
      could be the same due to the similar physiological role of COX-1 and COX-2
      dependent prostaglandins.

PMID- 12195420
TI  - [Macrohaematuria post-partum: an unusual case of acquired haemophilia after
      pregnancy].
AB  - BACKGROUND: Acquired hemophilia is a rare disorder due to spontaneous development
      of antibodies directed against the factor VIII molecule in patients with
      previously normal levels of factor VIII. In this paper we report an unusual case
      of acquired hemophilia admitted to our department of nephrology due to persisting
      gross hematuria. CASE REPORT: A 38-year-old primigravida woman, previously fit
      and well, had an uncomplicated pregnancy, labor and a caesarean delivery at 38
      weeks of gestation. Two weeks after delivery she developed gross hematuria with
      anemia. She was therefore admitted to a department of urology where urinary
      system and hematological investigation did not reveal important anomalies. Due to
      persisting gross hematuria and suspected kidney disease, the patient was admitted
      to our department of nephrology where serious anemia and prolongation of aPTT
      were noted; factor VIII procoagulant activity was low with a Bethesda assay
      confirming the presence of anti human f VIII antibody. Diagnosis of acquired
      hemophilia was confirmed and treated with corticosteroid therapy, intravenous
      immunoglobulins and recombinant factor VIII. After 10 days, gross hematuria
      stopped with improvement of aPTT and level of factor VIII. DISCUSSIONS: It is
      postulated that pregnancy leads to an altered immune status whereby the F VIII
      from the embryo, through transplacental leakage, may be considered as a foreign
      antigen by the mother, leading to the formation of antibodies. Bleeding symptoms
      usually became apparent within 3 months of delivery but could be as late as 12
      months post-delivery and sometimes coagulation investigation results are normal
      at the beginning. It is therefore very important to estimate many times the
      activated partial thromboplastin time in macrohematuria post-partum. Mortality
      due to hemorrhage varies between 14 and 22 % in previous series. In the vast
      majority complete remission is achieved spontaneously within a few months. The
      diagnosis of acquired hemophilia is of fundamental importance for an adequate
      treatment preventing serious complications and high mortality.

PMID- 12195421
TI  - [Analysis of urinary sediments in a nephrological laboratory: a precious art but
      too expensive?].

PMID- 12195422
TI  - Distal ureter morphogenesis depends on epithelial cell remodeling mediated by
      vitamin A and Ret.
AB  - Almost 1% of human infants are born with urogenital abnormalities, many of which
      are linked to irregular connections between the distal ureters and the bladder.
      During development, ureters migrate by an unknown mechanism from their initial
      integration site in the Wolffian ducts up to the base of the bladder in a process
      that we call ureter maturation. Rara(-/-) Rarb2(-/-) mice display impaired
      vitamin A signaling and develop syndromic urogenital malformations similar to
      those that occur in humans, including renal hypoplasia, hydronephrosis and mega
      ureter, abnormalities also seen in mice with mutations in the proto-oncogene Ret.
      Here we show that ureter maturation depends on formation of the 'trigonal wedge',
      a newly identified epithelial outgrowth from the base of the Wolffian ducts, and
      that the distal ureter abnormalities seen in Rara(-/-) Rarb2(-/-) and Ret(-/-)
      mutant mice are probably caused by a failure of this process. Our studies
      indicate that formation of the trigonal wedge may be essential for correct
      insertion of the distal ureters into the bladder, and that these events are
      mediated by the vitamin A and Ret signaling pathways.

PMID- 12195423
TI  - BRCA1 induces DNA damage recognition factors and enhances nucleotide excision
      repair.
AB  - Inheritance of a mutation in the gene BRCA1 confers on women a 50-85% lifetime
      risk of developing breast cancer. Mutations in the TP53 tumor-suppressor gene are
      found in 70-80% of BRCA1-mutated breast cancer but only 30% of those with
      wildtype BRCA1 (ref. 3). The p53 protein regulates nucleotide excision repair
      (NER) through transcriptional regulation of genes involved in the recognition of
      adducts in genomic DNA. Loss of p53 function results in deficient global genomic
      repair (GGR), a subset of NER that targets and removes lesions from the whole
      genome. Here we show that BRCA1 specifically enhances the GGR pathway,
      independent of p53, and can induce p53-independent expression of the NER genes
      XPC, DDB2, and GADD45. Defects in the NER pathway in BRCA1-associated breast
      cancers may be causal in tumor development, suggesting a multistep model of
      carcinogenesis.

PMID- 12195424
TI  - Targeted mutation of Cyln2 in the Williams syndrome critical region links CLIP
      115 haploinsufficiency to neurodevelopmental abnormalities in mice.
AB  - Williams syndrome is a neurodevelopmental disorder caused by the hemizygous
      deletion of 1.6 Mb on human chromosome 7q11.23. This region comprises the gene
      CYLN2, encoding CLIP-115, a microtubule-binding protein of 115 kD. Using a gene
      targeting approach, we provide evidence that mice with haploinsufficiency for
      Cyln2 have features reminiscent of Williams syndrome, including mild growth
      deficiency, brain abnormalities, hippocampal dysfunction and particular deficits
      in motor coordination. Absence of CLIP-115 also leads to increased levels of CLIP
      170 (a closely related cytoplasmic linker protein) and dynactin at the tips of
      growing microtubules. This protein redistribution may affect dynein motor
      regulation and, together with the loss of CLIP-115-specific functions, underlie
      neurological alterations in Williams syndrome.

PMID- 12195425
TI  - Mice heterozygous for mutation in Atm, the gene involved in ataxia
      telangiectasia, have heightened susceptibility to cancer.
AB  - Ataxia-telangiectasia is characterized by radiosensitivity, genome instability
      and predisposition to cancer. Heterozygous carriers of ATM, the gene defective in
      ataxia-telangiectasia, have a higher than normal risk of developing breast and
      other cancers. We demonstrate here that Atm 'knock-in' (Atm-Delta SRI)
      heterozygous mice harboring an in-frame deletion corresponding to the human
      7636del9 mutation show an increased susceptibility to developing tumors. In
      contrast, no tumors are observed in Atm knockout (Atm(+/-)) heterozygous mice. In
      parallel, we report the appearance of tumors in 6 humans from 12 families who are
      heterozygous for the 7636del9 mutation. Expression of ATM cDNA containing the
      7636del9 mutation had a dominant-negative effect in control cells, inhibiting
      radiation-induced ATM kinase activity in vivo and in vitro. This reduces the
      survival of these cells after radiation exposure and enhances the level of
      radiation-induced chromosomal aberrations. These results show for the first time
      that mouse carriers of a mutated Atm that are capable of expressing Atm have a
      higher risk of cancer. This finding provides further support for cancer
      predisposition in human ataxia-telangiectasia carriers.

PMID- 12195426
TI  - Where is 'where' in the human auditory cortex?
AB  - We examine the functional characteristics of auditory cortical areas that are
      sensitive to spatial cues in the human brain, and determine whether they can be
      dissociated from parietal lobe mechanisms. Three positron emission tomography
      (PET) experiments were conducted using a speaker array permitting quasi free
      field sound presentation within the scanner. Posterior auditory cortex responded
      to sounds that varied in their spatial distribution, but only when multiple
      complex stimuli were presented simultaneously, implicating this cortical system
      in disambiguation of overlapping auditory sources. We also found that the right
      inferior parietal cortex is specifically recruited in localization tasks, and
      that its activity predicts behavioral performance, consistent with its
      involvement in sensorimotor integration and spatial transformation. These
      findings clarify the functional roles of posterior auditory and parietal
      cortices, and help to reconcile competing models of auditory cortical
      organization.

PMID- 12195427
TI  - Neural adjustments to image blur.
AB  - Blur is an intrinsic feature of retinal images that varies widely across images
      and observers, yet the world still typically appears 'in focus'. Here we examine
      the putative role of neural adaptation in the human perception of image focus by
      measuring how blur judgments depended on the state of adaptation. Exposure to
      unfocused images has previously been shown to influence acuity and contrast
      sensitivity, and here we show that adaptation can also profoundly affect the
      actual perception of image focus.

PMID- 12195428
TI  - Mike or me? Self-recognition in a split-brain patient.
AB  - A split-brain patient (epileptic individual whose corpus callosum had been
      severed to minimize the spread of seizure activity) was asked to recognize
      morphed facial stimuli--presented separately to each hemisphere--as either
      himself or a familiar other. Both hemispheres were capable of face recognition,
      but the left hemisphere showed a recognition bias for self and the right
      hemisphere a bias for familiar others. These findings suggest a possible
      dissociation between self-recognition and more generalized face processing within
      the human brain.

PMID- 12195429
TI  - Spatial coding of position and orientation in primary visual cortex.
AB  - We examined the spatial distribution of population activity in primary visual
      cortex (V1) of tree shrews with optical imaging and electrophysiology. A line
      stimulus, thinner than the average V1 receptive field, evoked a broad strip of
      neural activity of nearly constant size for all stimulus locations tested within
      the central 10 degrees of visual space. Stimuli in adjacent positions activated
      highly overlapping populations of neurons; nevertheless, small changes in
      stimulus position produced orderly changes in the location of the peak of the
      population response. Statistically significant shifts in the population response
      were found for stimulus displacements an order of magnitude smaller than
      receptive field width, down to the limit of optical imaging resolution. Based on
      the pattern of population activity, we conclude that the map of visual space in
      V1 is orderly at a fine scale and has uniform coverage of position and
      orientation without local relationships in the mapping of these features.

PMID- 12195430
TI  - Stages of processing in face perception: an MEG study.
AB  - Here we used magnetoencephalography (MEG) to investigate stages of processing in
      face perception in humans. We found a face-selective MEG response occurring only
      100 ms after stimulus onset (the 'M100'), 70 ms earlier than previously reported.
      Further, the amplitude of this M100 response was correlated with successful
      categorization of stimuli as faces, but not with successful recognition of
      individual faces, whereas the previously-described face-selective 'M170' response
      was correlated with both processes. These data suggest that face processing
      proceeds through two stages: an initial stage of face categorization, and a later
      stage at which the identity of the individual face is extracted.

PMID- 12195431
TI  - Spatial memory dissociations in mice lacking GluR1.
AB  - Gene-targeted mice lacking the AMPA receptor subunit GluR1 (GluR-A) have deficits
      in hippocampal CA3-CA1 long-term potentiation. We now report that they showed
      normal spatial reference learning and memory, both on the hidden platform
      watermaze task and on an appetitively motivated Y-maze task. In contrast, they
      showed a specific spatial working memory impairment during tests of non-matching
      to place on both the Y-maze and an elevated T-maze. In addition, successful
      watermaze and Y-maze reference memory performance depended on hippocampal
      function in both wild-type and mutant mice; bilateral hippocampal lesions
      profoundly impaired performance on both tasks, to a similar extent in both
      groups. These results suggest that different forms of hippocampus-dependent
      spatial memory involve different aspects of neural processing within the
      hippocampus.

PMID- 12195432
TI  - Development of normal retinal organization depends on Sonic hedgehog signaling
      from ganglion cells.
AB  - The adult retina is organized into three cellular layers--an outer photoreceptor,
      a middle interneuron and an inner retinal ganglion cell (RGC) layer. Although the
      retinal pigment epithelium (RPE) and Muller cells are important in the
      establishment and maintenance of this organization, the signals involved are
      unknown. Here we show that Sonic hedgehog signaling from RGCs is required for the
      normal laminar organization in the vertebrate retina.

PMID- 12195433
TI  - Differential regulation of synaptic and extra-synaptic NMDA receptors.
AB  - A variety of processes limit NMDA (N-methyl-D-aspartate) receptor (NMDAR)
      activity in response to agonist exposure, including rundown--the decline of peak
      current with repeated, sustained agonist application. Here we report that calcium
      and tyrosine phosphorylation differentially regulate rundown of synaptic versus
      extrasynaptic NMDAR-mediated current in rat hippocampal pyramidal neurons.

PMID- 12195434
TI  - The sedative component of anesthesia is mediated by GABA(A) receptors in an
      endogenous sleep pathway.
AB  - We investigated the role of regionally discrete GABA (gamma-aminobutyric acid)
      receptors in the sedative response to pharmacological agents that act on GABA(A)
      receptors (muscimol, propofol and pentobarbital; 'GABAergic agents') and to
      ketamine, a general anesthetic that does not affect GABA(A) receptors. Behavioral
      studies in rats showed that the sedative response to centrally administered
      GABAergic agents was attenuated by the GABA(A) receptor antagonist gabazine
      (systemically administered). The sedative response to ketamine, by contrast, was
      unaffected by gabazine. Using c-Fos as a marker of neuronal activation, we
      identified a possible role for the tuberomammillary nucleus (TMN): when gabazine
      was microinjected directly into the TMN, it attenuated the sedative response to
      GABAergic agents. Furthermore, the GABA(A) receptor agonist muscimol produced a
      dose-dependent sedation when it was administered into the TMN. We conclude that
      the TMN is a discrete neural locus that has a key role in the sedative response
      to GABAergic anesthetics.

PMID- 12195435
TI  - Damaged epithelia regenerated by bone marrow-derived cells in the human
      gastrointestinal tract.
AB  - Studies have shown that bone marrow cells have the potential to differentiate
      into a variety of cell types. Here we show that bone marrow cells can repopulate
      the epithelia of the human gastrointestinal tract. Epithelial cells of male donor
      origin were distributed in every part of the gastrointestinal tract of female
      bone marrow transplant recipients. Donor-derived epithelial cells substantially
      repopulated the gastrointestinal tract during epithelial regeneration after graft
      versus-host disease or ulcer formation. Regeneration of gastrointestinal
      epithelia with donor-derived cells in humans shows a potential clinical
      application of bone marrow-derived cells for repairing severely damaged
      epithelia, not only in the gastrointestinal tract but also in other tissues.

PMID- 12195437
TI  - Impact of brain tumour treatment on quality of life.
AB  - Measurement of Health Related Quality of Life (HRQL) in brain tumour patients is
      important because brain tumours and brain tumour treatment usually affect
      physical, cognitive as well as emotional functioning. Measurement of HRQL is
      important for the understanding of disease burden and for the impact of specific
      tumour treatment. Quality of Life is a multidimensional concept consisting of
      physical, psychological and social phenomena. A large number of Quality of Life
      instruments have been developed. The European Organization for Research and
      Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) and the MOS
      Short-Form Health Survey are two frequently used general HRQL instruments. A
      specific brain tumour scale is the Brain Cancer Module, which is designed to be
      used in combination with general questionnaires. HRQL measurement and
      neuropsychological examination were used to investigate the impact of
      radiotherapy and surgery in low-grade glioma patients and the influence of tumour
      volume, tumour localization, performance status and age in both low-grade and
      high-grade glioma patients.

PMID- 12195436
TI  - Lethal H5N1 influenza viruses escape host anti-viral cytokine responses.
AB  - The H5N1 influenza viruses transmitted to humans in 1997 were highly virulent,
      but the mechanism of their virulence in humans is largely unknown. Here we show
      that lethal H5N1 influenza viruses, unlike other human, avian and swine influenza
      viruses, are resistant to the antiviral effects of interferons and tumor necrosis
      factor alpha. The nonstructural (NS) gene of H5N1 viruses is associated with this
      resistance. Pigs infected with recombinant human H1N1 influenza virus that
      carried the H5N1 NS gene experienced significantly greater and more prolonged
      viremia, fever and weight loss than did pigs infected with wild-type human H1N1
      influenza virus. These effects required the presence of glutamic acid at position
      92 of the NS1 molecule. These findings may explain the mechanism of the high
      virulence of H5N1 influenza viruses in humans.

PMID- 12195438
TI  - Excessive action monitoring in Tourette syndrome.
AB  - Tourette Syndrome (TS) has been related to hyperactive basal-ganglia
      thalamocortical pathways. This suggests that action monitoring might also be
      hyperactive. The present study used the event-related brain potential (ERP)
      technique to investigate this hypothesis. A simple "oddball" reaction time
      experiment was administered to a group of TS patients and a matched control
      group. In order to investigate variations in attentional allocation separate
      experimental runs were undertaken with target frequencies of 50% and 80%. The P3b
      component to targets was taken as an indicator of the target evaluation process
      and the response locked error-related negativity (ERN) served as an indicator of
      action monitoring. We hypothesized that the amplitudes of ERN and P3b would vary
      with respect to target frequency. The TS group would show an overall enhanced ERN
      but an unchanged P3b.ERN and P3b amplitudes were lower in the 80% target
      condition than in the 50% condition. In comparison with control subjects TS
      patients displayed an ERN of overall higher amplitude but with similar variations
      between target conditions. P3b amplitudes did not differ between groups. The data
      are interpreted to support the assumption of an abnormal action monitoring system
      in TS. A number of similarities to Obsessive-Compulsive Disorder are outlined and
      it is argued that the findings could be related to a hyperactive frontal-striatal
      thalamic-frontal circuit.

PMID- 12195439
TI  - Exclusion of linkage of nine neuronal nicotinic acetylcholine receptor subunit
      genes expressed in brain in autosomal dominant nocturnal frontal lobe epilepsy in
      four unrelated families.
AB  - Members of the ligand-gated neuronal nicotinic acetylcholine receptor (nAChR)
      gene family ( CHRNA4 and CHRNB2, coding for the alpha4 and beta2 subunits,
      respectively) are involved in autosomal dominant nocturnal frontal lobe epilepsy
      (ADNFLE). However, ADNFLE is genetically heterogeneous and mutations in CHRNA4
      and CHRNB2 account for only a minority of ADNFLE cases. Additional nAChR subunits
      expressed in the brain are candidates for this epilepsy. The involvement of all
      genes coding for brain-expressed nAChR subunits, with known chromosome
      localization ( CHRNB2, 1q21; CHRNA2, 8p21; CHRNA6, CHRNB3, 8p11.2; CHRNA7, 15q14;
      CHRNA5/A3/B4, 15q24 and CHRNA4, 20q13.2) was investigated in four unrelated
      ADNFLE Italian families for at least three generations. Families were selected on
      the basis of anamnestic and videopolysomnographic analyses. Individuals were
      typed for polymorphic markers located in the above mentioned chromosome regions.
      Linkage and mutation analyses were performed. In none of the families was linkage
      between ADNFLE and the analysed chromosome regions detected. These findings
      support the hypothesis that genes different from those coding for alpha2-7 and
      beta2-4 neuronal nAChR subunits could be responsible for ADNFLE.

PMID- 12195440
TI  - Visual event-related potential changes in two subtypes of multiple system
      atrophy, MSA-C and MSA-P.
AB  - We investigated the visual event-related potentials (ERPs) in two subtypes of
      multisystem atrophy (MSA) in 15 MSA-C patients, 12 MSA-P patients, and 21 normal
      control (NC) subjects. We used a visual oddball task to elicit ERPs. No
      significant changes were seen in N1 or N2 latency, in either MSA-C or MSA-P,
      compared with the NC group. An early stage of visual information process related
      to N1 and a visual discrimination process related to N2 might be preserved in
      both MSA-C and MSA-P. The P3a peak was more frequently undetectable in MSA than
      in the NC group. Significant P3a amplitude reduction in both MSA-C and MSA-P
      suggests impairment of the automatic cognitive processing in both MSA-C and MSA
      P. Significant difference was found in P3b latency and P3b amplitude only in MSA
      C, compared with the NC group. The result suggests the impairment of the
      controlled cognitive processing after the visual discrimination process in the
      MSA-C group. We further investigated the correlation between visual ERP changes
      and magnetic resonance imaging (MRI) data. Quantitative MRI measurements showed
      reduced size of the pons, cerebellum, perisylvian cerebral area, and deep
      cerebral gray matter in both MSA-C and MSA-P, and of the corpus callosum only in
      MSA-P, as compared to NC group. In both MSA-C and MSA-P, P3b latency was
      significantly correlated with the size on MRI of the pons and the cerebellum. P3b
      latency in the whole MSA group was also significantly correlated with the size of
      the pons and the cerebellum. These results indicate that P3b latency changes in
      parallel with the volume of the pons and the cerebellum in both MSA-C and MSA-P.

PMID- 12195441
TI  - Modafinil in treatment of fatigue in multiple sclerosis. Results of an open-label
      study.
AB  - BACKGROUND: Modafinil is a unique wake-promoting agent that is chemically
      distinct from traditional stimulants. Results of a placebo-controlled study
      showed it to improve fatigue in multiple sclerosis (MS) at a dose of 200 mg
      daily, but not at a dose of 400 mg daily. OBJECTIVE: To establish the efficacy,
      safety and appropriate dose of modafinil in the treatment of fatigue and
      sleepiness in patients with multiple sclerosis. METHOD: A total of 50 patients
      diagnosed with MS (mean age 40.4 +/- 10.3 years, 30 females/20 males; MS type: 36
      relapsing remitting, 1 primary progressive, 13 secondary progressive; mean
      disability level 3.8 +/- 1.5 on the Kurtzke EDSS) and complaining of chronic
      fatigue were enrolled in a prospective 3-month, two-center, open-label study.
      Efficacy was evaluated with the Fatigue Severity Scale (FSS, score range 0-42),
      the Epworth Sleepiness Scale (ESS, score range 0-24) and by subjective patient
      appraisal of change of fatigue, quality of life and overall satisfaction with
      treatment. Adverse effects (AEs) were recorded throughout the study. Treatment
      was started with a single daily dose of 100 mg in all patients. In non-responders
      the dose was increased by 100 mg increments up to a maximum daily dose of 400 mg.
      RESULTS: Three patients discontinued modafinil because of AEs (nervousness,
      dizziness). Two patients (4 %) were treated with 50 mg, 25 (50 %) with 100 mg, 21
      (42 %) with 200 mg and 2 (4 %) with 300 mg daily. No patient required 400 mg
      daily. Mean FSS scores were 30.3 +/- 8.5 at baseline and 25.4 +/- 3.7 at 3 months
      (p < 0.0001). Mean ESS scores were 9.7 +/- 3.9 at baseline and 4.9 +/- 2.9 at 3
      months (p < 0.0001). Self-appraisal of change of fatigue showed clear improvement
      in 41 patients (87.2 %), some improvement in 4 (8.5 %) and no change in 2 (4.3
      %). Overall clinical condition was clearly improved in 43 patients (91.5 %),
      somewhat improved in 1 patient (2.1 %), and unchanged in 3 patients (6.4 %). No
      patient reported worsening of overall clinical condition. CONCLUSIONS: Treatment
      with modafinil significantly improves fatigue and sleepiness and is well
      tolerated by patients with MS. Unlike the higher dose regimen required in
      narcolepsy, a low-dose regimen of modafinil is effective in MS.

PMID- 12195442
TI  - Percutaneous arterial interventional treatment of exercise-induced neurogenic
      intermittent claudication due to ischaemia of the lumbosacral plexus.
AB  - Radiological interventional therapy is described in seven patients with a
      distinct clinical syndrome of exercise-induced neurogenic intermittent
      claudication due to a reversible ischaemia of the lumbosacral plexus during
      walking accompanied by transient neurologic deficits. This condition was
      presumably caused by a reversible vascular steal phenomenon during exertion. The
      underlying vascular conditions were stenoses of the internal and/or common iliac
      arteries. All patients underwent percutaneous transluminal angioplasty (PTA)
      during the period from 1988 to 2001; an additional stent was placed in two
      patients. After a mean follow-up period of 18 months, four patients were
      asymptomatic, two had an improvement in walking-distance of 300 m and 800 m,
      respectively, and one patient developed a peripheral intermittent claudication
      without neurological complaints. In four patients, however, a further
      intervention was required. In patients with intermittent claudication due to
      exercise induced ischaemia of the lumbosacral plexus, a successful treatment is
      possible by means of PTA. Repeat intervention is justified if symptoms recur.

PMID- 12195443
TI  - Emotional processing in Parkinson's disease. A study using functional
      transcranial doppler sonography.
AB  - This study evaluated the use of transcranial Doppler ultrasonography for
      detecting selective changes in cerebral blood flow velocity during emotional
      processes. The aim was to investigate the possibility of obtaining functional
      information on the neuropsychology of emotions in patients with Parkinson's
      disease (PD). For this reason, blood flow velocity changes were investigated in
      both middle cerebral arteries (MCA) during a rest condition and when viewing non
      emotional (tasks 1 and 3) and emotional (task 2) slide sequences. The study
      included 12 PD patients and 12 healthy subjects. All patients were in treatment
      with levodopa or dopamine agonist. Investigation of PD patients was performed
      during an on-phase. The three tasks produced significantly different effects on
      the right and left side in the PD patients compared with the control group.
      During the two non emotion-related tasks the increase of mean flow velocity (MFV)
      compared with the basal values was similar in the two middle cerebral arteries in
      both groups [(PD Patients: Task 1: left MCA = 3.95 % 2.2, Right MCA = 4.33 % +/-
      2.3, Task 3: left MCA = 3.04 % +/- 1.9, Right MCA = 2.71 % +/- 2.2) (control
      group: Task 1: left MCA = 4.57 % +/- 1.4, Right MCA = 4.46 % +/- 1.7, Task 3:
      left MCA = 2.32 % +/- 0.9, Right MCA = 2.52 % +/- 1.2)] The negative emotional
      task was accompanied by a significantly higher increase in the right (10.53 % +/-
      3.2) than in the left middle cerebral artery (4.52 % +/- 1.51) only in the
      control group. The PD patients showed a bilateral and symmetrical increase of MFV
      (left MCA = 4.28 % +/- 2.3 and right MCA 5.77 % +/-3.8). To determine whether
      there was a dysfunction in cerebrovascular reactivity and a deficit in the
      ability to activate both hemispheres in response to non emotion-related stimuli
      in the PD patients, the protocol study included a cerebrovascular reactivity test
      to apnea, a motor task (thumb-to-finger opposition), a cognitive task (word
      fluency and visual discrimination of objects), performed by both patients and
      controls. The pattern of MFV changes during these tasks was not statistically
      significantly different in the two experimental groups. In order to evaluate the
      possible influence of drug treatment on cerebrovascular reactivity, seven
      patients were also evaluated during an off-phase, after a 48-hour wash-out
      period. Changes in MFV during every task were similar to that observed during the
      on-phase. These findings show the possibility of obtaining specific functional
      information from bilateral transcranial Doppler and suggest the selective and
      specific deficit of PD patients in emotional processing.

PMID- 12195444
TI  - sICAM-1 is not a marker for disease activity in the relapse-free interval of
      multiple sclerosis--a cross-sectional pilot study.
AB  - In multiple sclerosis (MS), serum levels of ICAM-1 were elevated during acute
      exacerbations and were therefore proposed as a marker of disease activity, but
      the potential of this molecule as an indicator of long-term activity, i. e. the
      progression of the disease outside acute exacerbations, is not known. We
      therefore measured sICAM-1 levels by an enzyme-linked immunosorbent assay in 26
      patients with active relapsing-remitting (RR) MS (at least two relapses in the
      preceding 2 years, but not within the last 30 days), in 10 patients with active
      secondary-progressive MS (progression of at least one point on the EDSS and/or
      two relapses in the preceding 2 years, but not within the last 30 days), in 8
      patients with stable RR MS (no relapse and no progression during the last two
      years), and in 16 healthy controls. There was no significant difference between
      the different MS subtypes and healthy controls, nor within the different MS
      subtypes. Thus, while sICAM-1 may be useful to indicate short-term activity of MS
      in terms of relapses and MRI activity, this does not hold true for the long-term
      activity of MS outside acute exacerbations.

PMID- 12195445
TI  - Chronic corticosteroid administration causes mitochondrial dysfunction in
      skeletal muscle.
AB  - Corticosteroid myopathy is a major clinical problem in patients undergoing
      chronic corticosteroid treatment and shows insidious and progressive muscle
      atrophy in proximal limbs. Although several mechanisms underlying the
      pathophysiology of muscle injury have been postulated, precise pathogenesis is
      still not clear. We evaluated the mitochondrial functions in patients receiving
      corticosteroids compared with those in healthy controls or patients not receiving
      corticosteroids. The serum levels and total production of lactate were
      investigated by an aerobic exercise test using a bicycle ergometer. Mitochondrial
      respiratory activities and oxidative damage in biopsied skeletal muscles were
      also studied. The results of aerobic exercise tests revealed a significant
      overproduction of lactate in patients treated with corticosteroids ( p < 0.005),
      which was positively correlated with total corticosteroid doses administered ( p
      < 0.0001). In these patients, mitochondrial enzyme activity in complex I was
      significantly decreased ( p < 0.05) and oxidative damage of biopsied skeletal
      muscle was remarkable both in mitochondrial and nuclear DNAs ( p < 0.001). The
      results suggest that chronic corticosteroid administration induces mitochondrial
      dysfunction and oxidative damage in skeletal muscles, which may be the
      pathogenesis, at least in part, of corticosteroid-induced myopathy.

PMID- 12195446
TI  - Relationship between urinary symptoms and disease-related parameters in multiple
      sclerosis.
AB  - OBJECTIVE: To find the prevalence of voiding dysfunction in patients with
      multiple sclerosis and to examine the relationship between the voiding
      dysfunction and various parameters of the disease (disease severity, disease
      duration, lesion site, age and sex). METHODS: Using the International prostate
      symptom score, lower urinary tract symptoms were quantitatively evaluated in all
      patients with multiple sclerosis who had visited our neurological department
      during three months. The lesion site in the central nervous system was determined
      by a combination of neurological and magnetic resonance imaging findings.
      RESULTS: Of the 47 patients who had completed the questionnaire, 25 (53 %) were
      considered to have symptomatic voiding dysfunction. Even at early stage of the
      disability, 6 of 19 (32 %) patients were symptomatic. Eight (17 %) patients had
      irritative urinary symptoms alone, whereas 9 (19 %) patients had obstructive
      urinary symptoms alone. The irritative and obstructive symptoms were concomitant
      in 10 (21 %) patients. Compared with reports from Western countries, the ratio of
      obstructive symptoms to irritative symptoms was high in Japan. The degree of
      irritative symptoms was well correlated with the disease severity, whereas the
      correlation of obstructive symptoms with the disease severity was less
      significant. Irritative symptoms also showed a weak correlation with the disease
      duration, but obstructive symptoms did not. Among the lesion sites in the central
      nervous system, only the presence of the spinal cord lesion was related to the
      degree of urinary symptoms. Urinary symptoms were not significantly influenced by
      the age or the sex. Quality of life was disturbed by urinary symptoms, and this
      disturbance paralleled the disease severity. CONCLUSION: Urinary symptoms,
      especially irritative symptoms, reflect the condition of the disease. Thus, the
      quantified urinary symptoms may assist neurological diagnosis.

PMID- 12195447
TI  - Normal dopamine transporter binding in dopa responsive dystonia.
AB  - We report the clinical manifestations of dopa responsive dystonia (DRD) in 2
      patients from the same family. The brain magnetic resonance images (MRI) were
      normal. The dopamine transporter (DAT) imaging with (99m)Tc-TRODAT-1 was
      performed in the 2 probands, 8 patients with young onset Parkinson disease (YOPD)
      and 16 normal controls. The ratios of (99m)Tc-TRODAT-1 brain SPECT in the
      striatum were 2.40 +/- 0.12 (right) and 2.30 +/- 0.17 (left) in these 2 DRD
      patients as compared with 1.38 +/- 0.18 (right), 1.41 +/- 0.20 (left) in YOPD
      patients, and 2.15 +/- 0.35 (right), 2.14 +/- 0.32 (left) in normal controls
      respectively. A normal DAT uptake was found in DRD suggesting a normal
      presynaptic nigrostriatal dopaminergic terminal. We conclude that a normal DAT in
      parkinsonian patients can differentiate DRD from YOPD. In addition, DAT with
      (99m)Tc-TRODAT-1 is a reliable and convenient tool to study the function of the
      presynaptic dopaminergic axonal terminals.

PMID- 12195448
TI  - Determinants of lumbar CSF protein concentration.
AB  - OBJECTIVE: To determine factors influencing the wide variation of protein
      concentration in lumbar cerebrospinal fluid (CSF). METHODS: Patient variables
      with potential influence on spinal CSF flow and resorption were measured in
      different patient settings and compared with albumin and IgG CSF/serum quotients.
      RESULTS: In patients whose diagnostic lumbar puncture produces normal CSF the
      albumin quotient increased with body mass index (r = 0.408), abdominal
      circumference (r = 0.399), and body weight (r = 0.317), age-corrected with
      partial correlation. Body motion before lumbar puncture showed only marginal
      influence on albumin quotient. In patients with radiculography the albumin
      quotient decreased with iodine contrast medium elimination from spinal
      subarachnoid space (r = -0.598) and increased with narrowing of lumbosacral
      spinal canal (r = 0.515). CONCLUSION: Correlation of albumin quotient with body
      mass index and related variables may be mediated by spinal CSF resorption, which
      should be impaired in overweight patients with elevated venous pressure. Negative
      correlation of albumin quotient with iodine resorption from spinal CSF supports
      this assumption. Correlation of albumin quotient with narrowing of lumbosacral
      canal should be due to slowed spinal CSF flow which does increase protein
      concentration. Tested variables explain part of variation of CSF protein
      concentration. Other variables like blood-CSF barrier permeability and pulsatile
      spinal CSF flow should have additional influence.

PMID- 12195449
TI  - The impact of outpatient rehabilitation on quality of life in multiple sclerosis.
AB  - It is well accepted that rehabilitative treatment can be effective in reducing
      disability and optimizing quality of life (QoL) of people with multiple sclerosis
      (MS). The aim of this study was to evaluate the effects of a comprehensive
      outpatient rehabilitative treatment on QoL in patients suffering from MS. We
      selected 111 patients from a sample of 407 patients who had consecutively entered
      the MS Center of Catania (which is located in southern Italy) in 1998. Fifty
      eight were randomly assigned to the study treatment and 53 to a waiting list
      (control treatment). Kurtzke's EDSS and quality of Life (QoL)were the primary
      endpoints. QoL was measured with the generic multi-item SF-36 scales. We also
      used: the Beck Depression Inventory (BDI) for depression, the Tempelaar Social
      Experience Check-list (SET) for social activities and the Fatigue Impact Scale
      (FIS). The study treatment group was treated for 6 consecutive weeks, 6 days a
      week with a comprehensive rehabilitative outpatient model. The control treatment
      group was in a waiting list and was trained to self-exercises at home. EDSS
      remained unchanged in both groups. All health related QoL domains significantly
      improved in the study treatment (p < 0.001 in physical functioning, role
      physical, bodily pain, general health, and social functioning; p < 0.05 in
      vitality, role emotional and mental health). FIS, SET and BDI also improved
      significantly after the rehabilitative treatment in the study group (p < 0.001).
      The results of this study confirm the effectiveness of a short comprehensive
      outpatient model of rehabilitative treatment in people with MS and in particular
      in their QoL.

PMID- 12195450
TI  - Low prevalence of ataxic polyneuropathy in a community with high exposure to
      cyanide from cassava foods.
AB  - INTRODUCTION: Ataxic polyneuropathy, which occurs in endemic form in an area in
      southwest Nigeria, is attributed to exposure to cyanide from cassava foods.
      Exposure to cyanide from cassava is, however, not exclusive to this endemic area.
      In this study, the occurrence of ataxic polyneuropathy was compared in two
      communities in Nigeria, one located in the endemic area and the other located
      outside the endemic area. Both communities have been shown to have high exposure
      to cyanide from cassava foods. METHOD: The prevalence of ataxic polyneuropathy in
      Jobele, Nigeria, a community located outside the endemic area, was compared with
      the prevalence of ataxic polyneuropathy in Ososa, Nigeria, a reference community
      located in the endemic area. Subjects aged 10 years and above in both communities
      were screened for ataxic polyneuropathy. Ataxic polyneuropathy was diagnosed if
      sensory gait ataxia and sensory polyneuropathy were present. The intake of
      cassava foods, biomarkers of exposure to cyanide, and intake of protein and
      sulphur were measured. RESULTS: Prevalence of ataxic polyneuropathy were 490 per
      10,000 in Ososa, and 17 per 10,000 in Jobele. The age-adjusted prevalence ratio
      is 4 (95% CI 0-9). The mean intake of all cassava foods in Jobele was 7
      meals/person/week (95% CI 6-8), while the mean intake of all cassava foods in
      Ososa was 10 meals/person/week (95 % CI 9-11). The concentration of thiocyanate
      in the plasma was above the reference limit in 65% (95% CI 57-73) in Jobele, and
      40 % (95% CI 27-52) in Ososa. The intake of protein was significantly lower in
      Ososa than in Jobele, but the concentrations of glutathione, cysteine and gamma
      glutamylcysteine in the plasma were within the same range in Jobele and Ososa.
      CONCLUSION: This study shows that the occurrence of ataxic polyneuropathy is low
      in a community where exposure to cyanide is high. This suggests that exposure to
      cyanide is not a direct cause of ataxic polyneuropathy.

PMID- 12195451
TI  - Electrophysiological brainstem testing in the diagnosis of reversible brainstem
      ischemia.
AB  - The aim of this study was to evaluate the sensitivity of multimodal
      electrophysiological brainstem testing in the diagnosis of clinically suspected
      reversible ischemic deficits of the brainstem compared with diffusion weighted MR
      imaging. We investigated 158 consecutive patients presenting with signs of acute
      brainstem dysfunction. Serial electrophysiological brainstem tests including
      masseter reflex, blink reflex, masseter inhibitory reflex, AEP, MEP, EOG and the
      oculoauricular phenomenon were applied. In 14 of the 158 patients neurological
      deficits resolved in less than 24 hours, which was suggestive of a transitory
      ischemic attack (TIA), 19 patients had brainstem signs for more than 24 hours but
      less than 1 week, suggestive of a reversible ischemic neurological deficit
      (RIND). Electrophysiological data indicated acute functional brainstem lesions in
      54,5 % of patients with transient clinical brainstem impairment. Lesion detection
      rate was significantly higher when combining electrophysiological data and MRI
      (60,4 %) than using acute brainstem abnormalities in diffusion weighted MRI alone
      (39,4 %). We conclude that diffusion weighted MRI and electrophysiological
      brainstem testing are complimentary sensitive indicators of acute brainstem
      lesions in patients with reversible neurological deficits. Correct identification
      of brainstem ischemia influences the therapeutic regimen and may improve patient
      outcome.

PMID- 12195452
TI  - Increased lymphocyte death by neglect-apoptosis is associated with lymphopenia
      and autoantibodies in lupus patients presenting with neuropsychiatric
      manifestations.
AB  - To evaluate lymphocyte death by neglect-apoptosis features in systemic lupus
      erythematosus (SLE) patients presenting with neuropsychiatric (NPSLE) involvement
      we studied 40 SLE patients with active disease, 20 with and 20 without
      neuropsychiatric manifestations, and 20 control individuals. Lymphocyte apoptosis
      was evaluated by means of DNA staining using flow cytometry, immediately after
      cell isolation and after incubation with culture medium or autologous serum.
      Compared with controls, NPSLE and non-NPSLE patients exhibited increased rates of
      neglect-apoptosis immediately after cell isolation. Only NPSLE patients exhibited
      an increased neglect-apoptosis rate after incubation with culture medium;
      however, the neglect-apoptosis rate was associated with lymphopenia in both
      series of patients. After lymphocyte incubation with autologous serum, only NPSLE
      patients exhibited a significant negative correlation between the neglect
      apoptosis rate and the number of peripheral lymphocytes. The incubation of
      lymphocytes with autologous serum containing antiphospholipid or anti-SSA/Ro
      antibodies significantly increased the neglect-apoptosis in NPSLE when compared
      with non-NPSLE patients with a similar autoantibody profile. In conclusion, NPSLE
      and non-NPSLE patients shared several abnormalities in terms of lymphocyte
      neglect-apoptosis. Peculiar findings were observed in NPSLE patients particularly
      after incubation with autologous serum, such as the fact that the increased
      lymphocyte death by neglect-apoptosis was associated with lymphopenia and with
      the presence of antiphospholipid and anti-SSA/Ro antibodies.

PMID- 12195453
TI  - Intensified PCV-chemotherapy with optional stem cell support in recurrent
      malignant oligodendroglioma.
AB  - Six patients with recurrent or progressive anaplastic oligodendroglial tumors
      after surgical treatment and irradiation were treated with six/seven cycles of
      intensified PCV: Vincristine (1 mg/m(2)), CCNU (50 mg/m(2)) d.1,15 and
      procarbazine (75 mg/m(2)) d.2 to 29. If leukocytopenia (< 2.500/microl) or
      thrombocytopenia (< 75.000/microl) developed, 1 x 10(6) CD34(+) autologous stem
      cells/ kg body weight were reinfused three days after completion of subsequent
      cycles. Complete response was seen in 2/6 and partial response in 4/6 patients.
      Median follow up from time of recurrence was 35 months, progression free survival
      was 18 to > 39 months and overall survival 23 to > 39 months. We conclude that
      intensified PCV with stem cell support is feasable in recurrent/progressive
      anaplastic oligodendroglial tumors and appears to be sufficiently well tolerated
      to allow further study.

PMID- 12195454
TI  - Combination therapy with interferon beta-1b and azathioprine in secondary
      progressive multiple sclerosis. A two-year pilot study.
AB  - Combination therapy may benefit the subgroup of patients with secondary
      progressive multiple sclerosis (SPMS) who do not respond to interferon beta
      (IFNB). We performed a two-year study of azathioprine (AZA) combined with IFNB-1b
      in SPMS patients who had not responded well to IFNB-1b alone. Patients with SPMS
      were eligible for this non-controlled prospective study if they had two or more
      relapses requiring corticosteroid treatment or deteriorated by at least 0.5
      points on the Expanded Disability Status Scale (EDSS) while on IFNB-1b in the
      year preceeding the study. Patients were to continue treatment with IFNB-1b (8
      MIU qod, subcutaneous) and received AZA (50 mg tid, oral). Safety was assessed in
      terms of adverse reactions and laboratory measures graded according to the WHO
      toxicity scale. Efficacy was explored by changes in relapse rate, EDSS, 9-hole
      peg test (9-HPT), neuropsychological scores, and magnetic resonance imaging (MRI)
      results. Neutralizing antibodies (NAB) were measured. Ten SPMS patients (6
      females) with a median EDSS score of 4.5 were enrolled. One patient withdrew
      because of gastrointestinal complaints, one was withdrawn owing to poor
      compliance, and 8 patients completed therapy. The only frequent side effect was
      lymphopenia, reported at least once in all patients. Annual relapse rate was
      reduced by approximately 50 % in the second year. There was a significant trend
      for EDSS increase. Total lesion load measured by MRI decreased at 12 and 24
      months; only one patient had active lesions. No changes were seen in the 9-HPT.
      There was a significant improvement in neuropsychological tests after 24 months (
      p = 0.045). One patient tested positive for NAB throughout the study, and
      transient NAB were detected in 4 patients. In conclusion, combination therapy
      with IFNB-1b and AZA was safe and generally well tolerated in patients with SPMS.
      Strict clinical and laboratory monitoring is recommended during this combination
      therapy.

PMID- 12195455
TI  - Reversible white matter alterations in encephalopathy associated with autoimmune
      thyroid disease.
AB  - Encephalopathy associated with autoimmune thyroid disease is an underdiagnosed
      clinical condition. No specific disease marker exists and to date, imaging
      techniques have not proven useful. The disease is characterized by seizures,
      stroke-like events and psychiatric symptoms. Here, we present the report of a
      patient with encephalopathy associated with autoimmune thyroid disease in which a
      reversible white matter disorder was detected by MR imaging. This encephalopathy
      was alleviated and later disappeared following corticosteroid treatment. We
      conclude that the white matter is the principal brain tissue involved in this
      condition and that brain MRI studies may prove to be a useful tool in the
      diagnosis of patients suffering this treatable disease.

PMID- 12195456
TI  - Is visual field constriction in epilepsy patients treated with vigabatrin
      reversible?
AB  - OBJECTIVE: To evaluate the reversibility of vigabatrin associated visual field
      constriction. BACKGROUND: Visual field constriction (VFC) occurs in approximately
      40 % of epilepsy patients under treatment with vigabatrin (VGB). There is still
      controversy about whether VGB-associated VFC is reversible. From a cross
      sectional study there is evidence that VFC does not reverse three to six months
      after stopping VGB treatment. So far, there are no long term studies on this
      subject. METHODS: We performed a follow-up study on 15 epilepsy patients (eight
      women, seven men, median age 45 (21-58) years) with VGB-associated VFC but
      otherwise normal ophthalmological examination. Kinetic and static perimetry was
      performed one and two years after VFC was diagnosed (baseline examination).
      Visual field size at first and at second year-follow-up was compared with the
      baseline examination. Because discontinuation of VGB-treatment was dependant on
      clinical needs, patients either stopped VGB treatment before or after VFC was
      diagnosed. In a small group of patients VGB treatment was continued despite of
      VFC. RESULTS: There was no statistically significant difference in visual field
      size comparing baseline values with first year and second year follow-up
      examinations either in patients who stopped VGB treatment (n = 11) or in patients
      who continued VGB treatment on a reduced dosage (n = 4). CONCLUSION: Although our
      data are based on a relatively small group of patients there is evidence that VFC
      resulting from VGB treatment is not reversible in epilepsy patients after
      stopping the drug.

PMID- 12195457
TI  - MR correlates of cerebral atrophy in patients with multiple sclerosis.
AB  - OBJECTIVE: To investigate the in-vivo correlates of brain atrophy in patients
      with multiple sclerosis (MS) by assessing the relationship between normalized
      measures of brain volume (NBV) and other magnetic resonance (MR) measures of
      tissue damage. BACKGROUND: Brain atrophy diffusely occurs and progressively
      increases in patients with MS. Nevertheless, the mechanisms leading to brain
      atrophy in this disease are not fully understood. METHODS: MR examinations were
      performed in 20 patients with relapsing-remitting MS. Conventional MRI was used
      to assess NBV and total brain T2-hyperintense and T1-hypointense lesion volumes.
      Proton MR spectroscopic imaging and diffusion tensor MR imaging were also
      performed for large portions of brain containing mainly normal-appearing tissue
      to provide indices of tissue damage, including N-acetylaspartate to creatine
      ratio (NAA/Cr) and mean diffusivity (D). RESULTS: Values of NBV correlated
      significantly with those of average brain (r = -0.58, p = 0.007) and NAA/Cr (r =
      0.67, p < 0.001). The relationship of these markers of tissue damage to NBV was
      also found when NAA/Cr and were computed together in a composite MR score (r =
      0.70, p < 0.001). In contrast, NBV values did not correlate with measurements of
      average lesion, T(2) and T(1) weighted total brain MRI lesion volumes.
      CONCLUSIONS: This study suggests that brain atrophy in MS is not simply due to
      axonal loss, but rather reflects a more generalized process that involves various
      brain tissue components. Damage to the normal-appearing tissue rather than the
      extent and intrinsic pathology of macroscopic lesions seems to be important in
      the destructive process leading to MS-related irreversible cerebral atrophy.

PMID- 12195458
TI  - Idiopathic intracranial hypertension in pregnancy.
AB  - OBJECTIVE: Since idiopathic intracranial hypertension (IIH) is most prevalent in
      obese women of childbearing age, concerns arise regarding the impact of pregnancy
      on the disorder and the potential teratogenicity of some therapeutic agents. We
      evaluated the course, management of pregnant IIH patients and the visual and
      pregnancy outcomes. METHODS: Case series of pregnant women diagnosed with IIH.
      IIH symptoms, neuro-ophthalmological findings, IIH management, visual and
      pregnancy outcomes were documented. RESULTS: Among 240 women with IIH, 12 had 16
      pregnancies. Ten had headaches, five had transient visual obscurations, and three
      had diplopia. Visual acuity was severely decreased in one and mildly reduced in
      three women. Six had marked and six had mild bilateral papilledema. Visual field
      loss occurred in four women. Visual symptoms and loss improved for the duration
      of the pregnancy after diagnostic lumbar puncture and salt restricted diet in
      three. Two additional women needed continuous spinal drainage for two days. One
      woman was treated with acetazolamide and medical abortion. The one woman with
      severe vision loss had fenestration of one optic nerve sheath and a
      lumboperitoneal shunt as well as corticosteroids and was the only case with
      permanent field loss. After intervention, visual acuity improved in all cases
      with reduced vision. There were 10 full-term normal deliveries, three missed
      abortions, one therapeutic abortion and two intrauterine fetal deaths.
      CONCLUSIONS: IIH appears to present during the first two trimesters of pregnancy
      with typical symptoms and findings. Visual outcome is similar as for non-pregnant
      women. Treatment should be oriented towards dietary control, without ketosis.
      Repeated spinal fluid drainage, if needed, can be helpful.

PMID- 12195459
TI  - Correlation between automated writing movements and striatal dopaminergic
      innervation in patients with Wilson's disease.
AB  - Handwriting defects are an early sign of motor impairment in patients with
      Wilson's disease. The basal ganglia being the primary site of copper accumulation
      in the brain suggests a correlation with lesions in the nigrostiatal dopaminergic
      system. We have analysed and correlated striatal dopaminergic innervation using
      [(123)I]beta-CIT-SPECT and automated handwriting movements in 37 patients with
      Wilson's disease. There was a significant correlation of putaminal dopaminergic
      innervation with fine motor ability (p < 0,05 for NIV [number of inversion in
      velocity], NIA [number of inversion in acceleration], frequency). These data
      suggest that loss of dorsolateral striatal dopaminergic innervation has a
      pathophysiological function for decreased automated motor control in Wilson's
      disease. Furthermore analysis of automated handwriting movements could be useful
      for therapy monitoring and evaluation of striatal dopaminergic innervation.

PMID- 12195461
TI  - Stroke, cerebral artery dissection, and cervical spine manipulation therapy.
AB  - Stroke represents an infrequent adverse reaction associated with cervical spine
      manipulation therapy. Attempts to identify the patient at risk and the type of
      manipulation most likely to result in these complications of manipulation have
      not been successful. A retrospective review of 64 medical legal cases of stroke
      temporally associated with cervical spine manipulation was performed to evaluate
      characteristics of the treatment rendered and the presenting complaints in
      patients reporting these complications. These files included records from the
      practitioner who administered the manipulation therapy, post stroke testing and
      treatment records usually by a neurologist, and depositions of the patient and
      the practitioner of manipulation as well as expert and treating physicians. A
      retrospective review of the files was carried out by three (two in 11 cases)
      researchers using the same data abstraction instrument to independently assess
      each case. These independent reviews were followed by a consensus review in which
      all reviewers reached agreement on file content. Ninety two percent of cases
      presented with a history of head and/or neck pain and 16 (25 %) cases presented
      with sudden onset of new and unusual headache and neck pain often associated with
      other neurological symptoms that may represent a dissection in progress. The
      strokes occurred at any point during the course of treatment. Certain patients
      reporting onset of symptoms immediately after first treatment while in others the
      dissection occurred after multiple manipulations. There was no apparent dose
      response relationship to these complications. These strokes were noted following
      any form of standard cervical manipulation technique including rotation,
      extension, lateral flexion and non-force and neutral position manipulations. The
      results of this study suggest that stroke, particularly vertebrobasilar
      dissection, should be considered a random and unpredictable complication of any
      neck movement including cervical manipulation. They may occur at any point in the
      course of treatment with virtually any method of cervical manipulation. The
      sudden onset of acute and unusual neck and/or head pain may represent a
      dissection in progress and be the reason a patient seeks manipulative therapy
      that then serves as the final insult to the vessel leading to ischemia.

PMID- 12195460
TI  - Hematopoietic stem cell transplantation for multiple sclerosis. A retrospective
      multicenter study.
AB  - RATIONALE: Phase I/II studies of autologous hematopoietic stem cell
      transplantation (HSCT) for multiple sclerosis ( MS) were initiated, based on
      results of experimental transplantation in animal models of multiple sclerosis
      and clinical observations in patients treated concomitantly for malignant
      disease. PATIENTS: Eighty-five patients with progressive MS were treated with
      autologous HSCT in 20 centers and reported to the autoimmune disease working
      party of the European Group for Blood and Marrow Transplantation (EBMT). 52 (61
      %) were female, median age was 39 [20-58] years. The median interval from
      diagnosis to transplant was 7 [1-26] years. Patients suffered from severe disease
      with a median EDSS score of 6.5 [4.5-8.5]. Active disease prior to transplant was
      documented in 79 of 82 evaluable cases. RESULTS: The stem cell source was bone
      marrow in 6 and peripheral blood in 79, and stem cells were mobilized into
      peripheral blood using either cyclophosphamide combined with growth factors or
      growth factors alone. Three patients experienced transient neurological
      complications during the mobilization phase. The high dose regimen included
      combination chemotherapy, with or without anti-lymphocyte antibodies or, with or
      without, total body irradiation. The stem cell transplants were purged of
      lymphocytes in 52 patients. Median follow-up was 16 [3-59] months. There were 7
      deaths, 5 due to toxicity and infectious complications, 2 with neurological
      deterioration. The risk of death of any cause at 3 years was 10 (+/-7)% (95 %
      confidence interval). Neurological deterioration during transplant was observed
      in 22 patients; this was transient in most but was associated with MS progression
      in 6 patients. Neurological improvement by > or = 1 point in the EDSS score was
      seen in 18 (21 %) patients. Confirmed progression-free survival was 74 (+/-12)%
      at 3 years being 66 (+/-23)% in patients with primary progressive MS but higher
      in patients with secondary progressive or relapsing-remitting MS, 78 (+/-13)%; p
      = 0.59. The probability of confirmed disease progression was 20 (+/-11)%. MRI
      data were available in 78 patients before transplant showing disease activity
      (gadolinium enhancing, new or enlarging lesions) in 33 %. Posttransplant MRI
      showed activity at any time in 5/61 (8 %) evaluable cases. CONCLUSION: Autologous
      HSCT suggest positive early results in the management of progressive MS and is
      feasible. These multicentre data suggest an association with significant
      mortality risks especially in some patient groups and are being utilised in the
      planning of future trials to reduce transplant related mortality.

PMID- 12195462
TI  - Cerebrovascular complications of therapeutic neck manipulation. The need for
      reliable data on risks and risk factors.

PMID- 12195463
TI  - Nontraumatic abdominal emergencies: acute abdominal pain: diagnostic strategies.
AB  - Common causes of acute abdominal pain include appendicitis, cholecystitis, bowel
      obstruction, urinary colic, perforated peptic ulcer, pancreatitis,
      diverticulitis, and nonspecific, nonsurgical abdominal pain. The topographic
      classification of acute abdominal pain (pain in one of the four abdominal
      quadrants, diffuse abdominal pain, flank or epigastric pain) facilitates the
      choice of the imaging technique. The initial radiological evaluation often
      consists of plain abdominal radiography, despite significant diagnostic
      limitations. The traditional indications for plain films--bowel obstruction,
      pneumoperitoneum, and the search of ureteral calculi--are questioned by helical
      computed tomography (CT). Although ultrasonography (US) is in many centers the
      modality of choice for imaging the gallbladder and the pelvis in children and
      women of reproductive age, CT is considered to be one of the most valued tools
      for triaging patients with acute abdominal pain. CT is particularly beneficial in
      patients with marked obesity, unclear US findings, bowel obstruction, and
      multiple lesions. The introduction of multidetector row CT (MDCT) has further
      enhanced the utility of CT in imaging patients with acute abdominal pain.

PMID- 12195464
TI  - Non-traumatic abdominal emergencies: imaging of acute intestinal obstruction.
AB  - The purpose of this paper is to give an overview of the main clinical questions
      in bowel obstruction, to discuss the value of various imaging modalities,
      including conventional radiography, ultrasound, and CT, to underline the impact
      of imaging in the management of patients with suspect bowel obstruction, and then
      to suggest a diagnostic triage in such patients.

PMID- 12195465
TI  - Non-traumatic abdominal emergencies: imaging and intervention in gastrointestinal
      hemorrhage and ischemia.
AB  - Radiologist and radiological techniques play a crucial role in imaging and
      interventional procedures in gastrointestinal hemorrhage and ischemia. They are
      involved in emergency situations that may lead to the death of the patient.
      Therefore correct diagnosis and treatment are absolutely decisive. We have a
      great potential in tools of diagnosis, with angiography serving not only as the
      gold standard for diagnosis even offering a potentially effective treatment for
      various pathologies. Nevertheless, other techniques have developed greatly during
      the past decade, including in standard protocols for the management of vascular
      pathologies such as those discussed here. Ultrasound, computed tomography, and
      magnetic resonance imaging and their applications in the vascular field such as
      in as Doppler ultrasound, computed tomography angiography, and magnetic resonance
      angiography provide sensitivity as high as that of angiography for detecting
      vascular-dependent lesions and for evaluating and excluding other causes of acute
      or chronic abdomen disorders. This contribution evaluates clinical aspects,
      various imaging techniques, and interventional effectiveness related to
      gastrointestinal hemorrhage and ischemia.

PMID- 12195466
TI  - Non-traumatic abdominal emergencies: imaging and intervention in sepsis.
AB  - Cross-sectional imaging, in particular CT, has become the main method of
      detecting abdominal collections. Indium-labelled white-cell scintigraphy and
      gallium scintigraphy are reserved for patients in whom there is a high clinical
      suspicion of abdominal sepsis but CT has not revealed a source of sepsis.
      Scintigraphy is also used in patients with suspected vascular graft infections or
      suspected infected hip prostheses. Percutaneous abscess drainage (PAD) has
      revolutionised the treatment of abdominal abscesses over the past 20 years, with
      repeat laparotomy for postoperative abscesses becoming a rare event. Ultrasound
      or CT can be used to guide PAD. Choosing an access route that does not cross
      intervening organs is of crucial importance to the safe performance of PAD. The
      Trocar or Seldinger techniques can be used with equal success. The cavity should
      be aspirated until dry and irrigated with saline. Repeat imaging after drainage
      is helpful to detect any undrained locules. PAD endpoints include patient
      defervescence, reduction in white blood cell count and catheter drainage of less
      than 10 ml per day. Details regarding PAD in specific abdominal regions are
      discussed. Success rates for PAD are high (close to 90%) in most abdominal
      organs. Slightly lower success rates are seen with PAD of pancreatic abscesses
      and abscesses associated with fistulas (60-85% success rates). Complication rates
      lie between 0% and 10%. Complications can be minimised by ensuring that the
      patient has broad spectrum antibiotic coverage before drainage, by carefully
      planning the access route and by ensuring diligent post-procedure care by
      radiology staff.

PMID- 12195467
TI  - Stereotactic breast biopsy with an 8-gauge, directional, vacuum-assisted probe:
      initial experience.
AB  - This study was prospectively conducted to assess the feasibility, safety and
      accuracy of an 8-G directional vacuum-assisted biopsy (DVAB) probe in the
      diagnostic management of nonpalpable breast lesions (NPBL). Of 170 planned
      procedures which were indicated for investigation of BI-RADS category-3 to
      category-5 lesions, 153 were performed in 138 consecutive patients. The probe was
      targeted by the stereotactic unit of a prone table (United States Surgical
      Corporation, Norwalk, Conn.; and Lorad, Danbury, Conn.). Four to 18 (mean 8) core
      specimens were obtained for each lesion. In case of complete removal of the
      lesion, a localizing clip was deployed at the biopsy site. Adequate material for
      histopathologic examination was obtained in all cases (100%). Four of 138 (3%)
      patients experienced mild hematomas. We observed 15 of 39 failures (38%) to place
      the localizing clips. Thirteen of 153 (8%) procedures were inconclusive and
      required reintervention. Following DVAB, 42 of 138 (30%) patients underwent
      surgery. Subject to incomplete follow-up of the entire cohort, we observed no
      false-positive and one false-negative diagnosis. These preliminary results
      suggest that DVAB using an 8-G probe are feasible, safe and accurate. In our
      experience, clip placement was problematic. It is probable that increasing the
      dimensions of DVAB will only be relevant in a limited number of clinical
      situations, primarily the desire to obtain complete radiologic resections of the
      target abnormality.

PMID- 12195468
TI  - Magnification mammography: a comparison of full-field digital mammography and
      screen-film mammography for the detection of simulated small masses and
      microcalcifications.
AB  - The objective of this study was a comparison of a full-field digital mammography
      (FFDM) system and a conventional screen-film mammography (SFM) system with
      respect to the detectability of simulated small masses and microcalcifications in
      the magnification mode. All images were obtained using 1.8 times magnification.
      The FFDM images were obtained at radiation dose levels of 1.39, 1.0, 0.7, 0.49
      and 0.24 times that of the SFM images. A contrast-detail phantom was used to
      compare the detection of simulated lesions using a four alternative forced-choice
      reader study with three readers. The correct observation ratio (COR) was
      calculated as the fraction of correctly identified lesions to the total number of
      simulated lesions. Soft-copy reading was performed for all digital images. Direct
      magnification images acquired with the digital system showed a lower object
      contrast threshold than those acquired with the conventional system. For equal
      radiation dose, the digital system provided a significantly increased COR (0.95)
      compared with the screen-film system (0.82). For simulated microcalcifications,
      the corresponding difference was 0.90 to 0.72. The digital system allowed equal
      detection to screen-film at 40% of the radiation dose used for screen film.
      Digital magnification images are superior to screen-film magnification images for
      the detection of simulated small masses and microcalcifications even at a lower
      radiation dose.

PMID- 12195469
TI  - Interobserver agreement and performance score comparison in quality control using
      a breast phantom: screen-film mammography vs computed radiography.
AB  - Our objective was to evaluate interobserver agreement and to compare the
      performance score in quality control of screen-film mammography and computed
      radiography (CR) using a breast phantom. Eleven radiologists interpreted a breast
      phantom image (CIRS model X) by four viewing methods: (a) original screen-film;
      (b) soft-copy reading of the digitized film image; (c) hard-copy reading of CR
      using an imaging plate; and (d) soft-copy reading of CR. For the soft-copy
      reading, a 17-in. CRT monitor (1024x1536x8 bits) was used. The phantom image was
      evaluated using a scoring system outlined in the instruction manual, and
      observers judged each object using a three-point rating scale: (a) clearly seen;
      (b) barely seen; and (c) not seen. For statistical analysis, the kappa statistic
      was employed. For "mass" depiction, interobserver agreement using CR was
      significantly lower than when using screen-film ( p<0.05). There was no
      significant difference in the kappa value for detecting "microcalcification";
      however, the performance score of "microcalcification" on CR hard-copy was
      significantly lower than on the other three viewing methods ( p<0.05). Viewing
      methods (film or CR, soft-copy or hard-copy) could affect how the phantom image
      is judged. Paying special attention to viewing conditions is recommended for
      quality control of CR mammograms.

PMID- 12195470
TI  - Breast augmentation and reconstructive surgery: MR imaging of implant rupture and
      malignancy.
AB  - The purpose of this study was to assess the diagnostic accuracy of MRI in
      detecting prosthesis integrity and malignancy after breast augmentation and
      reconstruction. Forty-one implants in 25 patients were analyzed by MRI before
      surgical removal. Imaging results were compared with ex vivo findings. Magnetic
      resonance imaging of the breast was performed on a 1.5-T system using a dedicated
      surface breast coil. Axial and sagittal T2-weighted fast spin-echo as well as
      dynamic contrast-enhanced T1-weighted gradient-recalled-echo sequences were
      acquired. The linguine sign indicating collapse of the silicone shell or
      siliconomas indicating free silicone proved implant rupture, whereas early focal
      contrast enhancement of a lesion was suspicious for malignancy. The sensitivity
      for detection of implant rupture was 86.7% with a specificity of 88.5%. The
      positive and negative predictive values were 81.3 and 92.0%, respectively. The
      linguine sign as a predictor of intracapsular implant rupture had a sensitivity
      of 80% with a specificity of 96.2%. Magnetic resonance imaging revealed two
      lesions with suspicious contrast enhancement (one carcinoma, one extra-abdominal
      fibromatosis). Magnetic resonance imaging is a reliable and reproducible
      technique for diagnosing both implant rupture and malignant lesions in women
      after breast augmentation and reconstruction.

PMID- 12195471
TI  - Invasive papillary carcinoma of the male breast.
AB  - Intracystic papillary carcinoma of the male breast is a very rare disease with
      only a few cases reported in the literature. A case is described and the
      additional value of MRI is discussed. To our knowledge, this is the first report
      regarding the MRI findings of an intracystic papillary carcinoma of the male
      breast.

PMID- 12195472
TI  - Comparative appearances of non-tuberculous mycobacteria species: a CT study.
AB  - Our objective was to characterise the CT features of the various species of non
      tuberculous mycobacteria (NTM) and to identify differences, if any, between
      Mycobacterium avium intracellulare( MAI) and other species. Fifty-five patients,
      who were culture positive on at least two occasions for a single NTM species,
      were evaluated. All patients had CT scans performed within 6 months of NTM
      identification. The CT scans were assessed for the presence and severity of
      bronchiectasis, nodules, cavities, tree-in-bud pattern, consolidation and for
      evidence of pre-existing lung disease. Bronchiectasis was identified in most
      patients (52 of 55, 95%) and nodules were present in approximately half (29 of
      55, 53%). Patients with MAI ( n=16) were found to have significantly higher
      bronchiectasis scores and higher prevalence of nodules than the other species
      (both p<0.01). Patients with M.kansasii ( n=9) and M.xenopi ( n=9) had cavities,
      tree-in-bud pattern, and pre-existing emphysema as the dominant CT features.
      Patients with M.chelonae and M.fortuitum were younger than the other groups and
      also had a high incidence of pre-existing lung disease. Patients with MAI
      infection have more severe bronchiectasis and more nodules on CT than the other
      NTM species. Morphological differences between the other species were identified
      but were less distinct.

PMID- 12195473
TI  - Radiological imaging as the basis for a simulation software of ventilation in the
      tracheo-bronchial tree.
AB  - The inhaled route is a promising new way for administering drugs to the human
      body. Flow and particle deposition in the human respiratory tract depends on the
      individual's anatomy as well as on the drug composition. A European Framework V
      Program supported project is currently developing a simulation tool for
      assessment of drug distribution and deposition. This tool relies heavily on the
      input of radiological data sets, which are obtained in humans. Both high temporal
      and spatial resolutions are required, and CT and MRI (including hyperpolarized
      helium-3 MRI) are applied. The radiological data are integrated into computation
      fluid dynamics software, which is capable of assessing air-flow profiles and
      compartmental behaviours. This is complemented by pharmacokinetic models, which
      should result in a simulation tool that will be of use for the theoretical design
      of new inhaled therapies. This article describes the special imaging requirements
      of each region of the respiratory tract and the feasibility of these
      sophisticated radiological techniques with a view of using these data in a
      simulation model of the lung.

PMID- 12195475
TI  - Computer-aided diagnosis in contrast-enhanced CT colonography: an approach based
      on contrast.
AB  - Automation in colorectal mass detection is achieved as soon as the voxels
      representing colorectal masses can be automatically segmented. We tested the
      Hounsfield (HU) value in intensely contrast enhanced high-resolution CT
      colonography for automated segmentation of colorectal masses in 18 patients with
      35 polyps (28 < 10 mm, 7 > or = 10 mm) and 7 carcinomas. Mean HU values of the
      colonic wall and masses were determined to deduce a gradient threshold for a
      segmentation process, which encodes the voxels bordering the colonic lumen with a
      colour ranging in intensity from 0 to 100% according to the selected gradient
      threshold range in the volume rendering. The results of the automated
      segmentation process were superimposed on a virtual double contrast and
      endoscopic display and validated through correlation with morphology. Mean HU
      values and their standard deviations for the colonic wall, polyps < 10 mm, polyps
      > or = 10 mm and carcinomas were 63 +/- 24, 154 +/- 38, 116 +/- 41 and 108+/-29
      HU, respectively. A gradient threshold ranging from 90 to 160 HU resulted in
      colour pools in 6 of 7 of polyps > or = 10 mm, and 6 of 7 carcinomas that were
      significant enough to prospectively guide the reader's attention to these masses.
      Due to the superposition of "false-positive" voxels in the projection view, the
      virtual endoscopic perspective was superior to the virtual double contrast
      display for controlling the segmentation results. The HU value is promising for
      automated segmentation of colorectal masses but needs to be combined with
      morphological parameters to render automated colorectal mass detection more
      accurate. Further refinements of the method with subsequent analysis of its
      accuracy, as well as analogue studies with contrast-enhanced MRI, appear
      warranted. More information at http://www.multiorganscreening.org

PMID- 12195474
TI  - Loss of FEV1 in cystic fibrosis: correlation with HRCT features.
AB  - The purpose of this study was to determine which high-resolution computed
      tomography (HRCT) features in patients with cystic fibrosis are most strongly
      associated with functional impairment as expressed by forced expiratory volume in
      one second (FEV1). Forty-seven patients with cystic fibrosis underwent chest HRCT
      and had pulmonary function tests. The HRCT examinations were evaluated for 11
      features scored using a modification of Bhalla system and FEV1 was recorded as
      percentage of the predicted value. Univariate and multivariate correlations
      between HRCT scores and FEV1 were performed. The most common HRCT feature was
      bronchiectasis (98%) followed by atelectasis-consolidation (81%), bronchial wall
      thickening (77%), tree-in-bud sign (74%), mucous plugging (72%) and mosaic
      perfusion pattern (47%). On univariate analysis the following features correlated
      strongly with FEV1: bronchial wall thickening ( p<0.0000001), tree-in-bud sign (
      p<0.0000001), mucous plugging ( p<0.0000001), atelectasis-consolidation
      (p<0.0000001), thickening of interlobular septa ( p<0.0002), severity ( p<0.0002)
      and extent of bronchiectasis ( p<0.0002). On multivariate analysis bronchial wall
      thickening and atelectasis-consolidation were the strongest independent
      determinants of the FEV1. We found a regression equation between FEV1 and the two
      HRCT features: FEV1=constant variable+a multiplied by bronchial wall thickening+b
      multiplied by atelectasis-consolidation (a and b=regression coefficients,
      R(2)=0.48). The major morphological determinants of functional abnormality in
      cystic fibrosis, as expressed by the loss of FEV1, are bronchial wall thickening
      and atelectasis-consolidation.

PMID- 12195476
TI  - Primary colorectal lymphoma: spectrum of imaging findings with pathologic
      correlation.
AB  - Primary colorectal lymphoma is a very uncommon disease; therefore, it has
      received little attention in the radiology literature. Moreover, imaging features
      of newly described pathologic subtypes have not been reported such as low-grade B
      cell lymphoma arising from mucosa-associated lymphoid tissue and peripheral T
      cell lymphoma that involves colorectal area. We retrospectively reviewed double
      contrast barium enema and CT scans in the patients with primary colorectal
      lymphoma. In this article the radiologic appearances of primary colorectal
      lymphoma are categorized into focal lesion and diffuse lesion. Focal lesion
      includes polypoid mass, circumferential infiltration with smooth mucosal surface,
      circumferential infiltration with extensive ulceration, cavitary mass, mucosal
      nodularity, and mucosal fold thickening. Diffuse lesion includes diffuse
      ulcerative lesion and diffuse nodular lesion. Peripheral T-cell lymphomas that
      involve the colon manifested as either a diffuse or focal segmental lesion and
      showed extensive mucosal ulceration. These findings are similar to those of
      Crohn's disease or tuberculous colitis and are different from those of previously
      reported colorectal lymphoma. Low-grade B-cell lymphoma arising from mucosa
      associated lymphoid tissue manifest as multiple mucosal nodularity. The imaging
      features of primary colorectal lymphoma are quite variable and overlap with other
      colonic pathology; however, it is important for radiologists to know the imaging
      features of primary colorectal lymphoma with their pathologic correlation.

PMID- 12195477
TI  - Use of an introducer sheath for colonic stent placement.
AB  - We describe a technical modification of Wallstent implantation for the treatment
      of malignant rectosigmoid and descending colonic obstructions. The modification
      is the routine placement of an introducer sheath via the rectum before stent
      implantation in order to straighten the rectosigmoid region. This device
      facilitates catheter and guide wire manipulations and obtaining specimen biopsies
      for histopathological studies. The introducer sheath has been used without
      complications in 21 consecutive patients.

PMID- 12195478
TI  - Multiplanar spiral CT enterography in patients with Crohn's disease using a
      negative oral contrast material: initial results of a noninvasive imaging
      approach.
AB  - The aim of this study was to prospectively define the role of multiplanar spiral
      CT enterography with a new negative oral contrast material for noninvasive
      assessment of the small bowel in patients with Crohn's disease. Thirty patients
      with established Crohn's disease prospectively underwent spiral CT enterography
      at 45-60 min after distension of the small bowel with 1400 ml of a negative oral
      contrast material (Mucofalk water enema). Spiral CT scans were obtained 50 s
      after administration of intravenous contrast material with the following
      parameters: 5-mm collimation; 7.5-mm/s table feed; and 3-mm reconstruction
      interval. The adequacy of bowel opacification, luminal distension, and the
      contribution of two-dimensional multiplanar reformatted imaging were assessed by
      two observers. Spiral CT imaging findings were compared with results of
      enteroclysis as well as endoscopic and histological findings in all patients.
      Spiral CT enterography with Mucofalk water enema was well tolerated in 29 of 30
      patients. Findings on spiral CT enterography were comparable with those of barium
      studies in 25 of 30 patients, superior to those on barium studies in 4 patients,
      and inferior in 1 patient ( p<0.05). The addition of multiplanar reformatted
      images to axial spiral CT scans significantly improved observers' confidence in
      image interpretation ( p<0.05) but did not reveal additional abnormalities.
      Multiplanar spiral CT enterography with Mucofalk excellently provides information
      in patients with Crohn's disease. This technique accurately depicts the level of
      small bowel obstruction and the extent of inflammatory small bowel disease and
      its extraluminal complications.

PMID- 12195479
TI  - How to detect hepatocellular carcinoma in cirrhosis.
AB  - Cirrhosis predisposes to hepatocellular carcinoma (HCC) which develops by
      sequential steps of de-differentiation of hepatocytes from regenerative nodules
      via borderline (dysplastic) nodules to frankly malignant HCC. Effective treatment
      depends on early recognition of HCC, so the key tasks for imaging are firstly
      recognising the presence of a suspicious lesion, and secondly differentiating
      between benign, borderline and malignant nodules. Screening of high-risk
      cirrhotic patients with sonography and measurement of alpha fetoprotein (AFP) is
      helpful but will not reliably differentiate small HCC from benign or dysplastic
      nodules. Large HCCs can usually be recognised by their characteristic morphology
      on imaging, but the appearances of smaller benign and malignant nodules show
      considerable overlap on unenhanced sonography, CT and MRI. Increasing degrees of
      histological malignancy are associated with increasing arterialisation and loss
      of portal blood supply, so the recognition of HCC requires the use of dynamic
      imaging with contrast-enhanced CT or T1-weighted MRI with gadolinium enhancement.
      Sonography with microbubble contrast media now offers another method for
      detecting arterialised nodules; however, some non-malignant nodules show arterial
      hypervascularity and a minority of HCCs are hypovascular, so the assessment of
      perfusion does not conclusively distinguish benign from malignant lesions.
      Kupffer cell function is another attribute of liver tissue which can be explored
      using MRI with superparamagnetic iron oxide particles (SPIO). Experience thus far
      suggests that uptake of SPIO is an effective discriminator between benign and
      malignant nodules. The combination of SPIO with gadolinium-enhanced MRI offers
      the opportunity for imaging characterisation of cirrhotic nodules by cellular
      function as well as by blood supply, and this approach is now proposed as the
      examination of choice for detecting HCC in cirrhosis.

PMID- 12195480
TI  - Discrimination of benign from malignant hepatic lesions based on their T2
      relaxation times calculated from moderately T2-weighted turbo SE sequence.
AB  - The differentiation of hemangioma from other hepatic neoplasms using MRI usually
      relies on the evaluation of heavily T2-weighted images. The aim of this study was
      to assess the value of T2-relaxation times calculated from moderately T2-weighted
      turbo spin-echo (TSE) sequence in characterization of focal hepatic lesions,
      including hepatic malignancies, focal nodular hyperplasia (FNH), hemangioma, and
      cyst. Fifty-two patients with 114 proven lesions (61 malignant masses, 6 focal
      nodular hyperplasias, 28 hemangiomas, 19 cystic lesions) were examined on 1.5-T
      system using a double-echo TSE sequence (TR=1800 ms; TE(eff) 1=40 ms; TE(eff)
      2=120 ms). Signal intensities (SI) of the liver as well as SI of all lesions were
      measured, and then the T2-relaxation times were calculated. The mean T2 time for
      the liver was 54 ms (+/-8 ms), for FNH 66 ms (+/-7 ms), for malignant hepatic
      lesions 85 ms (+/-17 ms), for hemangiomas 155 ms (+/-35 ms), and for cystic
      lesions 583 ms (+/-369) ms. Most malignant hepatic lesions were best
      differentiated between the thresholds of 67 and 116 ms, generating a sensitivity
      of 90% and a specificity of 94%. There were six false-negative diagnoses of
      malignant tumor and three false-positive cases (two hemangiomas and one FNH).
      Calculation of the T2-relaxation times obtained from the double-echo TSE sequence
      with moderate T2-weighting allowed differentiation between malignant and benign
      hepatic lesions with high sensitivity and specificity.

PMID- 12195481
TI  - Spontaneous resolution of a portal vein stenosis over a 21-month period in a
      "split-liver" transplant: demonstration by colour Doppler ultrasound, catheter
      angiography and splenic pulp pressures.
AB  - Portal vein stenosis in a "split-liver" transplant patient is demonstrated on
      colour Doppler ultrasound and indirect portography with raised splenic pulp
      pressures which resolves over a 21-month period without surgical or radiological
      intervention. When a portal vein stenosis in a liver transplant is encountered
      without severe derangement of liver function tests or signs of portal
      hypertension, regular follow-up colour Doppler ultrasound surveillance allows for
      evidence of spontaneous resolution.

PMID- 12195482
TI  - Cholecystoduodenal fistula in a porcelain gallbladder.
AB  - Calcification of the gallbladder wall (porcelain gallbladder) is rare. Its
      appearance is quite characteristic on plain films, ultrasonography and computed
      tomography. Sporadic cases of cholecystitis have been described in porcelain
      gallbladders. Enterobiliary fistula may complicate acute or chronic cholecystitis
      in non-calcified gallbladder. We report a unusual case of acute cholecystitis
      with cholecystoduodenal fistula in a porcelain gallbladder.

PMID- 12195483
TI  - Color Doppler appearance of penile cavernosal-spongiosal communications in
      patients with normal and impaired erection.
AB  - Our objective was to investigate prevalence and Doppler characteristics of penile
      cavernosal-spongiosal communications (CSC). These vessels are either anastomoses
      connecting the cavernosal arteries with the urethral arterial network or afferent
      vessels to the corpus spongiosum. Sixty-one consecutive patients underwent penile
      color Doppler US. Waveform changes in CSC were evaluated in comparison with
      changes in the cavernosal artery. Eighteen of 61 patients had normal erection, 17
      of 61 had arterial insufficiency, and 26 of 61 had veno-occlusive dysfunction.
      Resistance index (RI) in CSC was significantly lower than in cavernosal arteries
      in all patients and increased during phases 1-2 (positive diastolic flow). Peak
      systolic velocity (PSV) in CSC was significantly higher in the patients with veno
      occlusive dysfunction. During cavernosal phase 4 (diastolic flow reversal) CSC of
      patients with normal erection or with arterial insufficiency disappeared,
      underwent markedly reduced diastolic flow, or had systolic flow inversion.
      Conversely, low resistance flow was appreciable in CSC of patients with veno
      occlusive dysfunction who reached phase 4. During phase 5 (systolic peak
      reduction) all CSC disappeared. Color Doppler US allows evaluation of CSC both in
      patients with normal and impaired erection.

PMID- 12195484
TI  - Local staging of prostate cancer using magnetic resonance imaging: a meta
      analysis.
AB  - Our objective was to determine the influence of patient-, study design-, and
      imaging protocol characteristics on staging performance of MR imaging in prostate
      cancer. In an electronic literature search and review of bibliographies (January
      1984 to May 2000) the articles selected included data on sensitivity and
      specificity for local staging. Subgroup analyses examined the influence of age,
      prostate specific antigen, tumor grade, hormonal pre-treatment, stage
      distribution, publication year, department of origin, verification bias, time
      between biopsy and MR imaging; consensus reading, study design, consecutive
      patients, sample size, histology preparation, imaging planes, fast spin echo, fat
      suppression, endorectal coil, field strength, resolution, glucagon, contrast
      agents, MR spectroscopy, and dynamic contrast-enhanced MRI. Seventy-one articles
      and five abstracts were included, yielding 146 studies. Missing values were
      highly prevalent for patient characteristics and study design. Publication year,
      sample size, histologic gold standard, number of imaging planes, turbo spin echo,
      endorectal coil, and contrast agents influenced staging performance ( p=0.05).
      Due to poor reporting it was not possible to fully explain the heterogeneity of
      performance presented in the literature. Our results suggest that turbo spin
      echo, endorectal coil, and multiple imaging planes improve staging performance.
      Studies with small sample sizes may result in higher staging performance.

PMID- 12195485
TI  - Primary hydatid cyst in the retroperitoneal space: role of CT.
AB  - Localization of hydatid disease in the retroperitoneal space is extremely rare.
      We present the CT findings in a patient with echinococcal disease (E. Granulosus)
      in whom the cyst was localized to the retroperitoneum.

PMID- 12195486
TI  - Ultrasound anatomy in the normal neonatal and infant foot: an anatomic
      introduction to ultrasound assessment of foot deformities.
AB  - The aim of this study was to establish guidelines for US assessment of the talo
      crural, the talo-navicular and the calcaneo-cuboid joints during the first year
      of life, which could serve as a reference while studying foot deformities. The
      feet of 54 healthy children were examined at birth and at the age of 4, 7 and 12
      months by using three easily defined and reproducible US projections. With a
      medial projection the relation of the navicular in relation to the medial
      malleolus and the head of the talus was studied. A lateral projection revealed
      the calcaneo-cuboid relationship and a dorsal projection the talo-navicular
      alignment in the sagittal plane. Normal values for measurements of these
      cartilaginous relationships were established for the different age groups. Intra-
      and inter-observer reliability was assessed and found to be acceptable ( r=0.53
      0.90, Pearson correlation coefficient). With US it is possible to obtain
      reproducible planes of investigation that give reliable information about the
      talo-crural, the talo-navicular and the calcaneo-cuboid relationships during the
      first year of life.

PMID- 12195487
TI  - MR imaging of the normal appendix in children.
AB  - Our objective was to assess the ability of MR imaging in the detection of the
      normal appendix, and to describe the MR appearance of the normal appendix. There
      were 15 healthy volunteers (11 girls, 4 boys; mean age 12.3 years) who underwent
      MR imaging on a 1.0-T unit. The imaging protocol included axial and coronal T2
      weighted ultra turbo spin-echo (UTSE)-weighted images, axial T1-weighted turbo
      spin-echo (TSE) and coronal short tau inversion recovery (STIR)/TSE sequences.
      Confidence regarding the detection was scored from 1 (high confidence) to 3 (low
      confidence). Thickness was measured and MR appearance described. Clinical control
      after 2 weeks revealed no signs or symptoms of acute appendicitis. The normal
      appendix was seen in 86% on T2/UTSE-weighted images and in 73% on T1/TSE-weighted
      images and in none on STIR/TSE images. On axial T2/UTSE-weighted images, normal
      appendix had a hyperintense center and a hypointense wall, and was mostly
      hypointense on T1/TSE-weighted images, with a mean thickness of 4.5 mm. Magnetic
      resonance imaging seems to be an accurate method for the assessment of the normal
      appendix in children; thus, MR imaging might be an alternative to CT if US
      examinations are inconclusive.

PMID- 12195488
TI  - Digital subtraction in gadolinium-enhanced MR imaging of the brain: a method to
      reduce contrast dosage.
AB  - The aim of the study was to investigate the feasibility of using digital
      subtraction in contrast-enhanced MR imaging of the brain to reduce the MR
      contrast dosage without jeopardizing patient care. Fifty-two patients with
      intracranial lesions, either intra-axial or extra-axial, detected by computerized
      tomography were selected for contrast-enhanced MR imaging with half-dose and full
      dose of gadopentetate dimeglumine. The half-dose unsubtracted, full-dose
      unsubtracted, and half-dose subtracted MR images were visually assessed by
      counting the number of enhancing brain lesions in the images and quantitatively
      analyzed by computing their lesion contrast-to-background ratios (CBR). The
      visual conspicuity of the half-dose subtracted MR images was comparable to that
      of the full-dose unsubtracted MR images ( p>0.05), whereas the CBR of the half
      dose subtracted images was approximately two to three times higher than that of
      the full-dose unsubtracted images. The half-dose subtracted T1-weighted spin-echo
      images might be able to replace the conventional standard-dose T1-weighted spin
      echo images in MR imaging of the brain.

PMID- 12195489
TI  - Time course of the apparent diffusion coefficient after cerebral infarction.
AB  - The purpose of this study was to evaluate quantitative apparent diffusion changes
      in the center of infarction by measurement of the apparent diffusion coefficient
      (ADC), and to investigate the influence of ischemia on the contralateral
      hemisphere. By diffusion echo-planar imaging (EPI) 52 patients showing cerebral
      infarction were studied within 5 h to >12 months after onset of clinical
      symptoms. Using three diffusion gradient strengths (b1=30 s/mm(2); b2=300
      s/mm(2), b3=1100 s/mm(2)) ADC maps were generated. After onset of ischemia, ADC
      in the center of infarction was lower than in the contralateral regions of human
      brain. At first ADC declined for approximately 28 h to a minimum of approximately
      150x10(-8) cm(2)/s. Then the ADC reincreased and reached a "pseudonormalization"
      after approximately 5 days. Chronic infarctions did show much higher ADC values
      (2000x10(-8) cm(2)/s) than unaffected areas. Neither localization nor size of
      infarctions showed a significant influence on this time course. In the center of
      infarction diffusion is isotropic. Even brain regions of the contralateral
      hemisphere are influenced by cerebral ischemia. In these regions ADC is higher
      than for physiological conditions. The ADC also declines especially for the first
      2-3 days after onset of symptoms, also followed by reincrease. The ADC
      calculation enables determination of the onset of infarction more exactly than is
      possible using only diffusion-weighted imaging. Diffusion in the center of
      infarction is isotropic; hence, orientation of the diffusion gradients has no
      significant influence on sensitivity of measurements. The calculation of the ADC
      ratio based on data derived from the center of infarction and the contralateral
      hemisphere seems to be critical because the ADC in the unaffected contralateral
      hemisphere also changes.

PMID- 12195490
TI  - MR-angiogram-added surface anatomy scanning of superficial cerebral arteriovenous
      malformations.
AB  - Our purpose was to evaluate the utility of surface anatomy scanning (SAS) of the
      brain with superimposition of MR angiograms in the diagnosis and presurgical
      planning of superficial cerebral arteriovenous malformations (AVMs). We performed
      SAS in 15 patients with superficial cerebral AVMs. Two-dimensional phase-contrast
      MR angiograms were then obtained in the same section and superimposed on the SAS
      images. The images were assessed regarding the visualization of each AVM
      component using a four-point grading scale (3=excellent to 0=poor). In 13 of the
      patients, the assessment was made comparing with conventional angiograms. The
      images were also compared with the surgical findings in 5 patients. The added
      images agreed well with the angiographic findings and demonstrated the
      relationships between the AVM components and the adjacent brain surface. The
      average scores of the feeder(s), nidus, and drainer(s) were 2.27, 2.33, and 2.67,
      respectively. The surgical findings also correlated well with the added images.
      Our technique can noninvasively demonstrate superficial AVMs along with the brain
      surface and provide information useful for planning surgery.

PMID- 12195491
TI  - MRI-diffusion imaging of neuroblastomas: first results and correlation to
      histology.
AB  - The purpose of this study was to evaluate diffusion-weighted MR imaging in
      neuroblastomas. We prospectively examined seven children (age range 1-3 years)
      with seven solid body neuroblastomas. Diagnosis was established histologically.
      Diffusion-weighted echo-planar imaging (EPI) sequence was performed in all
      patients, with a repetition time of 5400 ms and an echo time of 103 ms, and with
      a b-value of 1000 s/mm(2). The contrast of tumour tissue depicted with T2
      weighted images and diffusion-weighted images were evaluated by means of region
      of-interest measurements and a calculation of the apparent diffusion coefficient
      (ADC) was done. The ADC calculation showed a mean ADC of 1.1x10(-3) (SD 0.14x10(
      3), range 0.9-1.2x10(-3)) mm(2)/s of all tumours. Diffusion-weighted images
      showed an increased tumour signal. Water proton diffusion within the tumour
      matrix of neuroblastomas is especially restricted by the molecular and
      macromolecular barriers due to the very dense structure of this tumour tissue. We
      hypothesize that high nuclear-to-cytoplasm ratio of neuroblastoma cells limits
      intracellular motion. Furthermore, the very densely packed tumour cells inhibit
      effective motion of extracellular water protons. Restricted proton motion leads
      to a reduction in the rate of apparent diffusion and to a marked increase in
      signal on diffusion-weighted EPI MR images.

PMID- 12195492
TI  - Congenital absence of the internal carotid artery diagnosed during investigation
      of trigeminal neuralgia.
AB  - Congenital absence of the unilateral internal carotid artery (ICA) was found in a
      patient during MR imaging examination for right trigeminal neuralgia. Magnetic
      resonance angiography showed complete absence of the right ICA and a large
      tortuous basilar artery (BA). The source images revealed a deformed right
      trigeminal nerve resulting from compression by the BA. Computed tomography of the
      skull base showed absence of the right carotid canal, suggesting agenesis of the
      right ICA. Longstanding hemodynamic stress may have caused the BA to become
      extremely tortuous, resulting in the trigeminal neuralgia.

PMID- 12195493
TI  - Nasolacrimal system: evaluation with gadolinium-enhanced MR dacryocystography
      with a three-dimensional fast spoiled gradient-recalled technique.
AB  - The aim of this study was to determine the diagnostic accuracy of gadolinium
      enhanced three-dimensional (3D) fast spoiled gradient-recalled (FSPGR) MR
      dacryocystography in patients with epiphora. Bilateral nasolacrimal systems of 19
      patients suspected of having nasolacrimal canal obstruction were evaluated with
      MR dacryocystography. A sterile 0.9% NaCl solution containing 1:100 diluted
      gadolinium chelate was instilled into the bilateral conjunctival sacs of the
      patients. The 3D FSPGR sequence was used with 1.0-T scanner with the following
      parameters: TR 9.3 ms; TE 2 ms; flip angle 20; 256x224 matrix; 13- or 26-cm field
      of view; and 1-mm slice thickness. Seventeen patients had digital
      dacryocystography for comparison which we considered standard of reference.
      Thirty-four nasolacrimal systems were evaluated with MR and digital
      dacryocystography. Discrepancies between the findings of both methods were
      detected in 2 patients. The overall sensitivity of MR in detecting the
      obstruction was 100%. Magnetic resonance helped to determine the canalicular and
      ductal obstruction in 100% of the patients and the saccular obstruction in 80% of
      the patients. We conclude that 3D FSGR technique for MR dacryocystography is a
      reliable and noninvasive method in the evaluation of the obstruction level in the
      lacrimal system in patients with epiphora.

PMID- 12195494
TI  - Cystic lymph node enlargement of the neck: filariasis as a rare differential
      diagnosis in MRI.
AB  - Cervical lymph node enlargement is a common feature of most inflammatory and
      neoplastic entities of the head and neck. Filariasis can lead to lymphangiectasis
      resembling lymph node enlargement; however, this is a rare differential diagnosis
      in European patients. As ethnic minorities are increasing throughout Europe and
      personal mobility, e.g. during holidays, is increasing, such rare differential
      diagnoses have to be taken into consideration. We present the case of an Iraqi
      patient referred to as for a suspected cystic lymph node mass that was verified
      histologically by open MRI biopsy and proved to be a cystic manifestation of
      filariasis.

PMID- 12195495
TI  - The role of diagnostic radiology in compressive and entrapment neuropathies.
AB  - Diagnostic imaging is increasingly being utilised to aid the diagnosis of
      compression and entrapment neuropathies. Cross-sectional imaging, primarily
      ultrasound and magnetic resonance imaging, can provide exquisite anatomical
      detail of peripheral nerves and the changes that may occur as a result of
      compression. Imaging can provide a useful diagnostic aid to clinicians, which may
      supplement clinical evaluation, and may eventually provide an alternative to
      other diagnostic techniques such as nerve conduction studies. This article
      describes the abnormalities that may be demonstrated by current imaging
      techniques, and critically analyses the impact of imaging in diagnosis of
      peripheral compressive neuropathy.

PMID- 12195496
TI  - MR imaging features of giant pre-sacral schwannomas: a report of four cases.
AB  - Benign giant sacral schwannoma is an uncommon cause of destruction of the sacrum.
      This report details four cases of a variant of this condition called giant
      presacral schwannoma (GPSS). On MR imaging the features are of a large, well
      defined presacral soft tissue mass, arising just to one side of the midline with
      minor involvement of the bone. The typical MR features of a benign peripheral
      nerve sheath tumour are not seen. The tumours appear heterogeneous due to long
      standing degeneration. Biopsy is advocated as the appearances of GPSS can be
      similar to a malignant peripheral nerve sheath tumour (malignant schwannoma).

PMID- 12195497
TI  - Lumbosacral interspinous ligament rupture associated with acute intrinsic spinal
      muscle degeneration.
AB  - The objective of this study was to demonstrate lumbosacral interspinous ligament
      rupture, with or without related acute intrinsic spinal muscle degeneration. This
      study consisted of a prospective imaging analysis of consecutive 100 MRI studies
      in adult patients (mean age 56 years) presenting with low back pain. Alterations
      from the normal in the inter- and perispinal structures of the spine and
      perispinal soft tissues (e.g., spinal ligaments, perispinal muscles) were sought
      based upon studies on young volunteers without low back pain ( n=10; mean age 23
      years). Compared with the group without low back pain, many index cases ( n=71,
      71%) demonstrated hyperintensity (i.e., sprain or frank ligamentous rupture) of
      the interspinous ligament(s) on T2-weighted, fat-suppressed MRI studies at one
      (20 of 71, 28%) or multiple (51 of 71, 72%) levels. Associated intrinsic spinal
      muscle (e.g., interspinalis, multifidus muscles) degeneration was observed in a
      minority of cases overall ( n=7, 7%), but was only seen in association with cases
      also demonstrating interspinous ligament degeneration/rupture (7 of 71, 10%).
      Lumbosacral interspinous ligament sprain or frank rupture, as well as related
      acute-subacute autotraumatic intrinsic spinal muscle rupture/degeneration, may be
      overlooked by many observers if fat-suppressed, T2-weighted MRI is not acquired.
      These musculoligamentous alterations are on occasion the only abnormalities
      recognized on MRI of the lumbosacral spine and may theoretically be sources of
      low back morbidity that potentially may respond to specific therapy. Because this
      study was an observational one, based solely upon medical imaging, future
      research must focus upon the correlation of the relevance of these findings with
      an age-matched asymptomatic control group and longitudinal clinicoradiologic
      therapeutic trials.

PMID- 12195498
TI  - Tumoral calcinosis presenting as an extradural mass: MR findings and pathological
      correlation.
AB  - Two cases of idiopathic tumoral calcinosis presenting as an extradural mass are
      reported. There are few reports in the literature of this pathological process
      presenting as extradural masses, so both cases represent very unusual locations
      for tumoral calcinosis. Magnetic resonance imaging features and pathological
      correlation of these two cases are presented. Tumoral calcinosis might be
      considered as a rare but possible cause of extradural mass.

PMID- 12195499
TI  - Digital radiography: are the manufacturers' settings too high? Optimisation of
      the Kodak digital radiography system with aid of the computed radiography dose
      index.
AB  - Manufacturers offer exposure indices as a safeguard against overexposure in
      computed radiography, but the basis for recommended values is unclear. This study
      establishes an optimum exposure index to be used as a guideline for a specific CR
      system to minimise radiation exposures for computed mobile chest radiography, and
      compares this with manufacturer guidelines and current practice. An
      anthropomorphic phantom was employed to establish the minimum milliamperes
      consistent with acceptable image quality for mobile chest radiography images.
      This was found to be 2 mAs. Consecutively, 10 patients were exposed with this
      optimised milliampere value and 10 patients were exposed with the 3.2 mAs
      routinely used in the department of the study. Image quality was objectively
      assessed using anatomical criteria. Retrospective analyses of 717 exposure
      indices recorded over 2 months from mobile chest examinations were performed. The
      optimised milliampere value provided a significant reduction of the average
      exposure index from 1840 to 1570 ( p<0.0001). This new "optimum" exposure index
      is substantially lower than manufacturer guidelines of 2000 and significantly
      lower than exposure indices from the retrospective study (1890). Retrospective
      data showed a significant increase in exposure indices if the examination was
      performed out of hours. The data provided by this study emphasise the need for
      clinicians and personnel to consider establishing their own optimum exposure
      indices for digital investigations rather than simply accepting manufacturers'
      guidelines. Such an approach, along with regular monitoring of indices, may
      result in a substantial reduction in patient exposure.

PMID- 12195502
TI  - MR microscopy of articular cartilage at 1.5 T: orientation and site dependence of
      laminar structures.
AB  - OBJECTIVE: To evaluate MR microscopic images of normal-appearing porcine hyaline
      cartilage ( n=15) in vitro obtained with an MR microscope using an independent
      console system (MRMICS) at 1.5 T. DESIGN AND RESULTS: The MRMICS is a portable
      imaging system consisting of a radiofrequency system, gradient power supplies and
      a personal computer. The images from the MRMICS showed a laminar structure of
      porcine cartilage similar to the structure demonstrated with other MR imaging
      techniques. The laminar structures of the articular cartilage, were, however
      heterogeneous in respect of signal intensity and thickness, which varied
      according to the site resected. The MR laminar appearance was most comparable to
      the staining with Masson's trichrome for collagen. CONCLUSION: MRMICS is a useful
      add-on system for obtaining microscopic MR images of articular cartilage in
      vitro.

PMID- 12195501
TI  - Malalignment at the Lisfranc joint: MR features in asymptomatic patients and
      cadaveric specimens.
AB  - OBJECTIVE: To assess the frequency of malalignment in the 1st, 2nd and 3rd tarso
      metatarsal joints (Lisfranc joint) in cadaveric specimen and asymptomatic
      individuals utilizing oblique axial MR images. DESIGN AND PATIENTS: Four fresh
      frozen cadaveric feet were dissected in the oblique axial plane at 5 mm slice
      thickness. Thirty MR studies in 29 patients who had no history of pain, trauma or
      surgery at the tarso-metatarsal area were included in our study. The 1st to 3rd
      tarso-metatarsal joints were evaluated on the MR studies and cadaveric slices by
      two musculoskeletal radiologists for (1) the presence of a medial and/or lateral
      step-off and (2) articular surface divergence. RESULTS: In the cadaveric
      dissections there were lateral step-offs in the 1st ( n=3) and in the 2nd ray (
      n=3) respectively. No joint incongruity was evidenced. The MR studies in the
      patients population depicted 28 step-offs (9 medial, 19 lateral) in the 1st ray,
      16 (2 medial, 14 lateral) in the 2nd ray and two in the 3rd ray. Joint
      incongruity was present in the 2nd ray ( n=6) and in the 3rd ray ( n=12). All the
      above findings were limited to a few images. CONCLUSIONS: Isolated joint
      malalignment with otherwise normal findings (no ligamentous injury, no fracture
      and no bone marrow edema) might reflect normal anatomic features at the tarso
      metatarsal joints and must be interpreted carefully.

PMID- 12195503
TI  - Nerve root sleeve diameters at normal segments and at segments with proximate
      disc disease: MRI evaluation.
AB  - OBJECTIVE: To compare MR morphologic parameters of spinal nerve roots and their
      range of variability in normal and abnormal spinal segments. DESIGN AND PATIENTS:
      Ninety-six consecutive lumbar spine MRI examinations were segregated into three
      groups: group 1 was composed of 30 patients with disc bulge, protrusion or
      extrusion at the L5-S1 segment measuring 3 mm or more; group 2 consisted of 31
      patients with no disc pathology; and group 3 was composed of 35 patients with no
      disc abnormality at the L5-S1 level but with coexisting spine pathology at other
      segments. Measurements of 192 S1 nerve root sleeves were performed at three
      consecutive levels on T1-weighted images. Differences between right and left
      nerve root sleeve diameters (delta value) at three slice levels were calculated
      in each group. Data were analyzed by ANOVA. RESULTS: No significant differences
      between the mean values of traversing S1 nerve root sleeve diameter on three
      corresponding consecutive slices were found among groups ( P=0.733, P=0.824,
      P=0.365 respectively), nor were significant differences in delta values between
      groups found ( P=0.639, P=0.113, P=0.722). CONCLUSIONS: S1 nerve root sleeve
      diameter and the differences between right and left in the abnormal group were
      not significantly different from normal and therefore can not be used as an
      objective criterion of nerve root pathology.

PMID- 12195504
TI  - Relationship between MRI and clinical findings in the acromioclavicular joint.
AB  - OBJECTIVE: To determine the relationship between the magnetic resonance (MR)
      appearance of the acromioclavicular (AC) joint and the physical findings. DESIGN:
      A total of 116 consecutive patients underwent routine MR imaging (MRI) of the
      shoulder over an 18-month period. All MR studies were interpreted by a blinded,
      experienced musculoskeletal radiologist. Eleven variables were studied: the
      presence of osteophytes; fluid in the joint; fluid outside the joint; high signal
      in the clavicle or in the acromion; fluid in the subacromial bursa; irregularity
      of the joint margins; bulging of the capsule; widening of the joint; the age of
      the patient; and the presence of a rotator cuff tear. The clinical information
      was supplied by an experienced shoulder surgeon blinded to the MRI findings. A
      control group of 23 normal volunteers was also studied. RESULTS: The only
      statistically significant correlation ( P=0.0249) was between high signal in the
      distal clavicle and degenerative changes found clinically. A weaker relationship
      existed between fluid in the joint and the clinical examination and between
      increasing degenerative changes and advancing age. Otherwise, no material
      relationship was found between any of the other MR abnormalities and the clinical
      picture. CONCLUSION: There appears to be no real correlation between the MR
      appearances and the clinical findings in the AC joint.

PMID- 12195505
TI  - Trabecular microstructure and surface changes in the greater tuberosity in
      rotator cuff tears.
AB  - OBJECTIVE: When planning surgery in patients with rotator cuff tear, strength of
      bone at the tendon insertion and trabecular bone structure in the greater
      tuberosity are usually taken into consideration. We investigated radiographic
      changes in bone structure of the greater tuberosity in rotator cuff tears.
      DESIGN: Twenty-two human cadaveric shoulders from subjects ranging from 55 to 75
      years of age were obtained. The integrity of the rotator cuff was examined by
      sonography to determine if it is intact without any tear, or torn partially or
      completely. The humeral head was sectioned in 3 mm thick coronal slab sections
      and microradiographed. After digitization of the microradiographs and imaging
      processing with in-house semi-automated image processing software tools developed
      using software interfaces on a Sun workstation, the trabecular
      histomorphometrical structural parameters and connectivity in the greater
      tuberosity were quantified. The degenerative changes on the surface of the
      greater tuberosity were interpreted blindly by 2 independent readers. RESULTS:
      Among the 22 shoulder specimens, the rotator cuff was found intact in 10
      shoulders, partially in 7 and fully torn in 5. Statistically significant loss in
      apparent trabecular bone volume fraction, number of trabecular nodes, and number
      of trabecular branches, and a statistically significant increase in apparent
      trabecular separation and number of trabecular free ends were found in the
      greater tuberosity of the shoulders with tears. The loss was greater in
      association with full tear than in partial tear. Thickening of the cortical
      margin of the enthesis, irregularity of its surface, and calcification beyond the
      tidemark were observed in 2 (20%) shoulders with intact rotator cuff, in 6 (86%)
      shoulders with partial tear, and in 5 (100%) shoulders with full tear.
      CONCLUSIONS: Rotator cuff tears are associated with degenerative changes on the
      bone surface and with disuse osteopenia of the greater tuberosity. Aging,
      degenerative enthesopathy of the supraspinatus tendon, and rotator cuff tears
      appear closely related.

PMID- 12195506
TI  - Posterior atlantoaxial dislocation without associated fracture.
AB  - We report on a 38-year-old man with post-traumatic posterior displacement of the
      atlas with respect to the axis without any associated fracture or neurological
      deficit caused by the displacement. Radiographs, computed tomography (CT) and
      magnetic resonance imaging (MRI) revealed posterior displacement of the atlas
      with the odontoid peg lying anterior and to the right of the anterior arch of the
      atlas.

PMID- 12195507
TI  - Intraoperatively proven anomalous Struthers' ligament diagnosed by MRI.
AB  - A case of median nerve entrapment at the elbow between the supracondylar process
      and an anomalous insertion of Struthers' ligament is presented. The diagnosis of
      anomalous insertion of the ligament was made by MRI and confirmed at operation.
      Struthers' ligament originated as usual from the supracondylar process but did
      not reach the medial epicondyle of the humerus, inserting instead in the brachial
      fascia above the epicondyle. The incomplete Struthers' ligament functioned,
      however, as a complete ligament. It produced symptoms identical to supracondylar
      process syndrome. Excision of the supracondylar process of the humerus and
      Struthers' ligament relieved symptoms in this athlete.

PMID- 12195508
TI  - Sonographic and MRI appearance of tensor fasciae suralis muscle, an uncommon
      cause of popliteal swelling.
AB  - A 20-year-old white man presented with a localized unilateral swelling in the
      popliteal fossa. Ultrasound (US) showed the presence of an accessory muscle, the
      tensor fasciae suralis. The muscle was located in the proximal portion of the
      popliteal fossa, superficial to the medial head of the gastrocnemius. Its long
      tendon extended inferiorly to join the Achilles tendon. Magnetic resonance images
      correlated well with the US findings, confirming the diagnosis. Tensor fasciae
      suralis muscle is a rare cause of popliteal swelling and must be differentiated
      from other masses. Both US and magnetic resonance imaging can diagnose it but we
      suggest US as the first-line technique in its evaluation.

PMID- 12195509
TI  - Ultrasonographic evaluation of congenital dislocation of the knee.
AB  - The authors describe ultrasonographic findings in a newborn girl with congenital
      dislocation of the knee (CDK). Ultrasonography showed a hyperechoic area and
      focal narrowing of the distal quadriceps as compared to the unaffected
      contralateral side, indicating the presence of fibrosis, which is the main
      pathologic feature of congenital dislocation of the knee. The hyperechoic area
      decreased after reduction of the dislocation and with patient growth.
      Ultrasonography was useful in evaluating CDK because it provided a direct view of
      the pathologic lesion, was painless, and did not involve exposure to X-rays.
      Further, we were able to serially evaluate the abnormal findings and provide
      advice regarding daily activity to the parents of the patient with CDK.

PMID- 12195510
TI  - Chondrosarcoma of the nasal septum.
AB  - The nasal septum is a particularly rare site of origin of chondrosarcoma. Cranial
      base invasion may be at hand, with such lesions making complete tumor removal
      difficult. MRI techniques allow precise definition of tumor extent. In the
      described case, CT and Dynamic MR imaging were performed in a case of
      chondrosarcoma of the nasal septum. Imaging clearly illustrated size and extent
      of the mass with central regions of internal calcification. Dynamic MRI was
      additionally performed, which helped to define the presumed origin of the lesion
      from the nasal septum.

PMID- 12195511
TI  - Chondrosarcoma of the larynx: treatment with radiotherapy.
AB  - The case of a 50-year-old man with chondrosarcoma of the larynx treated with
      radiotherapy is reported. The patient presented with hoarseness and dyspnea. He
      underwent computed tomography (CT), which demonstrated a soft tissue mass of the
      larynx. Direct laryngoscopy with biopsy established the diagnosis of
      chondrosarcoma. Although experience with radiotherapy in these cases has been
      lacking in the literature, it was considered and eventually used, as radical
      surgery would result in severe cosmetic and functional impairment. Radiation
      therapy alone resulted in long-term remission of the tumour for more than 3
      years. The patient has been followed up using CT and direct laryngoscopy for
      early detection of recurrence or metastases.

PMID- 12195512
TI  - Pelvic haemophilic pseudotumour: management of a patient with high level of
      inhibitors.
AB  - Haemophilic pseudotumour (HP) is a rare but very serious complication of
      haemophilia. HP affects mainly patients with severe haemophilia and those who
      have developed antibodies to factor VIII or factor IX. We report on a 45-year-old
      man with haemophilia A and high titres of inhibitors who developed an extensive
      HP with progressive destruction of the right ilium over a period of 12 years. The
      different therapeutic options (conservative management by replacement therapy,
      surgical approach, radiotherapy, percutaneous evacuation with secondary refilled
      cavity and transcatheter arterial embolization) are reviewed.

PMID- 12195513
TI  - Pseudoarthrosis and ankylosis of the vertebral spine without sacroiliitis
      associated with Takayasu's arteritis: review of the association.
AB  - Pseudoarthrosis and ankylosis of the vertebral spine associated with Takayasu's
      arteritis is extremely rare. We present a patient with the entity who was HLA-B27
      negative and had normal sacroiliac joints. The association between Takayasu's
      arteritis and ankylosing spondylitis appears real but seemingly rare.

PMID- 12195515
TI  - Temporal information for spatially constrained locomotion.
AB  - How is locomotion adapted to spatial environmental constraints? The control of
      this everyday behavior is claimed to be based on information that specifies
      either spatial or temporal properties of the actor-environment system. Although
      studies on open-loop locomotor pointing (i.e., the positioning of a foot on a
      target on the floor while walking) agree on the use of spatial information,
      studies on closed-loop locomotor pointing propose the use of temporal
      information. Here, we test the hypothesis of closed-loop locomotor pointing based
      on temporal information, by dissociating spatial and temporal information in a
      virtual reality setup (virtual environment connected to a treadmill). The results
      support this hypothesis and shed some light on the type of temporal information
      that is used. The performed dissociation between spatial and temporal
      information, however, does not rule out a control based on a continuous updating
      of spatial information. Therefore, our conclusion on the use of temporal
      information was moderated.

PMID- 12195516
TI  - The development of coordination for reach-to-grasp movements in children.
AB  - When adults reach to grasp stationary targets, movement kinematics (endpoint
      trajectories, interjoint coordination) are highly stereotyped and stable. The
      emergence of an optimal coordination for reaching involves mastering the
      redundant number of degrees of freedom while the body grows. Reaching has been
      well studied in healthy children under the age of 3 years. We characterised the
      development of coordination during reaching in children over the age of 3 years
      and identified age ranges in which stable patterns emerge. A random sample of 38
      healthy children aged 4-11 years and nine adults participated in the study. They
      reached from the seated position with the dominant arm and grasped a cone placed
      at three distances in the forward sagittal plane in front of the body. Kinematic
      data from markers placed on the arm, head and trunk were recorded at 100 Hz
      (Optotrak Motion Analysis System). Immature patterns of reaching were
      characterised by increased variability in younger compared to older children.
      Hand trajectories became smoother and less variable with age. Interjoint
      coordination became more consistent, while trunk displacement and variability
      decreased with age. Only children between 8 and 10 years old had variability
      similar to adults. Our data suggest that different aspects of movement kinematics
      mature at different rates. However, our data do not support the idea of a
      sequential maturation of different biomechanical variables.

PMID- 12195517
TI  - Physiological evidence for a possible projection from dorsal subiculum to
      hippocampal area CA1.
AB  - The substantial forward projection from hippocampal area CA1 to the subiculum has
      been comprehensively described, both anatomically and neurophysiologically. There
      are few data, however, regarding the existence of a backward projection from the
      subiculum to area CA1. We present here new electrophysiological evidence for the
      existence of this projection. We demonstrate a positive-going deflection in the
      evoked synaptic response in area CA1 following stimulation in dorsal subiculum.
      We also found a small, but significant, paired-pulse facilitatory effect at a 100
      ms interstimulus interval. We were unable to induce long-term potentiation
      following high-frequency stimulation, but were able to induce short-term
      potentiation.

PMID- 12195518
TI  - Audiotactile interactions in roughness perception.
AB  - The sounds produced when we touch textured surfaces frequently provide
      information regarding the structure of those surfaces. It has recently been
      demonstrated that the perception of the texture of the hands can be modified
      simply by manipulating the frequency content of such touch-related sounds. We
      investigated whether similar auditory manipulations change people's perception of
      the roughness of abrasive surfaces (experiment 1). Participants were required to
      make speeded, forced-choice discrimination responses regarding the roughness of a
      series of abrasive samples which they touched briefly. Analysis of discrimination
      errors verified that tactile roughness perception was modulated by the frequency
      content of the auditory feedback. Specifically, attenuating high frequencies led
      to a bias towards an increased perception of tactile smoothness. In experiment 2,
      we replicated the rubbing-hands manipulation of previous experimenters while
      participants rated either the perceived roughness or wetness of their hands. The
      wetness scale data replicated the results in the literature, while the roughness
      scale data replicated the result from experiment 1. A final experiment showed
      that delaying the auditory feedback from the hand-rubbing reduced the magnitude
      of this parchment-skin illusion. These experiments demonstrate the dramatic
      effect that auditory frequency manipulations can have on the perceived tactile
      roughness and moistness of surfaces, and are consistent with the proposal that
      different auditory perceptual dimensions may have varying salience for different
      surfaces.

PMID- 12195519
TI  - The role of stimulus type in age-related changes of visual working memory.
AB  - Aging is accompanied by increasing difficulty in working memory associated with
      the temporary storage and processing of goal-relevant information. Face
      recognition plays a preponderant role in human behavior, and one might therefore
      suggest that working memory for faces is spared from age-related decline compared
      to socially less important visual stimulus material. To test this hypothesis, we
      performed working memory (n-back) tasks with two different visual stimulus types,
      namely faces and doors, and compared them to tasks with primarily verbal
      material, namely letters. Age-related reaction time slowing was comparable for
      all three stimulus types, supporting hypotheses on general cognitive and motor
      slowing. In contrast, performance substantially declined with age for faces and
      doors, but little for letters. Working memory for faces resulted in significantly
      better performance than that for doors and was more sensitive to on-line
      manipulation errors such as the temporal order. All together, our results show
      that even though face perception might play a specific role in visual processing,
      visual working memory for faces undergoes the same age-related decline as it does
      for socially less relevant visual material. Moreover, these results suggest that
      working memory decline cannot be solely explained by increasing vulnerability in
      prefrontal cortex related to executive functioning, but indicate an age-related
      decrease in a visual short-term buffer, possibly located in the temporal cortex.

PMID- 12195520
TI  - Estimation of premotor synaptic drives to simulated abducens motoneurons for
      control of eye position.
AB  - The firing rate of an abducens motoneuron (AbMN) is linearly related to eye
      position with slope K, above recruitment threshold theta. Within the AbMN
      population K increases as theta increases. It is possible that these properties
      depend on the synaptic drives generated by the major premotor inputs to AbMNs,
      namely position-vestibular-pause (PVP) cells and eye and head velocity (EHV)
      cells in the medial vestibular nucleus, and eye-position and burst-position cells
      in the nucleus prepositus hypoglossi (NPH). Premotor inputs to AbMNs were
      therefore modelled by a two-layer net, in which the output nodes represented the
      AbMNs (with fixed intrinsic properties) and the input nodes the three classes of
      premotor units ( n=20/class). Conjugate eye-position commands were used to
      generate the firing rates in premotor units found experimentally. The output of
      the net was compared with observed AbMN firing rates, and the resultant error
      used to adjust the magnitude and sign of the connection weights between premotor
      units and AbMNs. To provide additional constraints on permitted weights, the net
      was also trained under simulated smooth pursuit, cancellation of the vestibular
      ocular reflex, and the vestibulo-ocular reflex itself (all at 0.5 Hz). Since the
      projections of EHV cells have not been clearly characterized, two versions of the
      model were trained, corresponding to different assumptions about these
      projections. In both versions, position-related AbMN firing rates were derived
      mainly from an excitatory drive from PVP cells and an inhibitory drive from NPH
      cells with the opposite ON direction. Variation in AbMN threshold theta and
      position sensitivity K depended on the strength of the drive from the NPH: the
      stronger the drive, the higher both K and theta. This arrangement was observed in
      six variants of the basic model with different parameter values, and in a
      simplified form (constant PVP drive and varying NPH drive) was able to generate
      qualitatively the observed relationship between K and theta even in the absence
      of input from EHV cells. It appears to be a robust mechanism for producing the
      experimentally observed variation in position-related firing of AbMNs, even
      without a contribution from their intrinsic properties, and predicts that local
      blocking of the inhibitory drive from cells in the NPH should lower both the
      position threshold and sensitivity of an individual AbMN. The model also
      indicates that if EHV cells have ipsilateral inhibitory projections, as has been
      proposed on the basis of their similarity with cells receiving input from the
      flocculus, then their role in eye-position control would reinforce that of cells
      in the NPH.

PMID- 12195521
TI  - Activation of intrinsic and extrinsic finger muscles in relation to the fingertip
      force vector.
AB  - Surface EMG was recorded from two intrinsic and two extrinsic muscles of the
      index finger during a two-dimensional isometric force task in the plane of
      flexion and extension. Subjects applied force isometrically at the fingertip in
      eight equally spaced directions, encompassing 360 degrees. Target forces spanned
      the range from 20% to 50% of maximum for each direction. The effect of varying
      the metacarpophalangeal (MCP) and interphalangeal (IP) joint angles was
      investigated. We found that when applying isometric force with the fingertip, the
      intrinsic muscles of the index finger behaved as a single unit whose region of
      activation overlapped that of the extrinsic flexor and extensor muscles. The
      activation region of the intrinsic muscles also spanned a range of force
      directions for which the extrinsic muscles were virtually inactive. The
      activation of all muscles, with the exception of the extrinsic extensor, was
      modified by changing the MCP and IP joint angles. Both IP flexion and MCP
      extension produced rotation of the resultant activity vector in the direction of
      MCP flexion. However, the relative rotation was much greater with IP flexion than
      MCP extension. The effect of IP flexion is linked to rotation of the force
      direction where joint torque switches from extension to flexion, while the effect
      of MCP extension is more likely related to changes in muscle length and MCP
      moment arm. Our results suggest that the primary role of intrinsic finger muscles
      is to precisely control the direction of fingertip force, while extrinsic muscles
      provide stability of the joints.

PMID- 12195522
TI  - Spatial constraints in bimanual coordination: influences of effector orientation.
AB  - Two experiments are reported that examined the influence of spatial orientation
      of the upper limbs in bimanual coordination. In both experiments, the upper limbs
      were oriented in either parallel, orthogonal, or obtuse spatial configurations
      and participants were asked to move their limbs continuously in temporal (1:1)
      synchrony, prepared in either in-phase or anti-phase modes of coordination.
      Bimanual coordination trials in Experiment 1 were paced by a metronome at one of
      four frequencies (1.0, 1.5, 2.0 or 2.5 Hz). Measures of relative phase accuracy
      and stability both revealed that, as metronome frequency increased, in-phase
      coordination dominated for the parallel spatial orientation, anti-phase
      coordination dominated for the orthogonal spatial orientation, and neither
      pattern dominated for the obtuse spatial orientations. In Experiment 2, an
      intentional switch method replicated and extended these influences of spatial
      orientation. The time to voluntarily switch from an anti-phase pattern to an in
      phase pattern was faster than an in-phase to anti-phase switch (confirming
      support for the dominance of the in-phase pattern), but this was true only for
      the parallel spatial orientation. The reverse was true for the orthogonal spatial
      orientation (i.e., faster from in-phase to anti-phase), and no difference in
      switch times was observed for an obtuse spatial orientation. These findings
      support and extend previous research regarding the influence of spatial
      orientation in bimanual coordination and may be attributed to the role of, and
      potential interactions between, egocentric, allocentric, and mechanical
      constraints during action.

PMID- 12195523
TI  - Opioid-insensitive hypoalgesia to mechanical stimuli at sites ipsilateral and
      contralateral to experimental muscle pain in human volunteers.
AB  - Musculoskeletal pains are often characterised by referred pain and hyperalgesia.
      The aim of the present study was to examine the sensitivity to pressure and
      pinprick at sites ipsi- and contralateral to capsaicin-induced pain in the
      tibialis anterior (TA) muscle. Visual analogue scale (VAS) scores of the
      sensation to sub- and supra-pain threshold stimuli by pressure and pinprick were
      recorded before, during and after experimental muscle pain. It was found that
      pressure stimulation (120% of baseline pain threshold) delivered over the
      ipsilateral deep peroneal nerve between the 1st and 2nd metatarsal bones showed a
      significant increase in VAS scores during muscle pain. The referred pain did not
      overlap this hyperalgesic site. Ipsilateral test sites at the TA muscle, great
      toe and between the 3rd and 4th metatarsal bones did not show any changes in
      response to pressure stimulation during pain. In contrast, test sites at the
      ipsilateral ankle showed hypoalgesia to pressure during muscle pain. In the
      contralateral leg hypoalgesia to pressure was found at all sites during pain. The
      decreased sensitivity to pressure was confirmed with both sub- and supra-pressure
      pain-threshold stimuli. VAS scores to pinprick were either decreased or unchanged
      during pain compared to before pain. Naloxone administrated in a placebo
      controlled manner had no effect on hypoalgesia to pressure or pinprick during
      muscle pain. Thus, the generalised decreased sensitivity may reflect activation
      of non-opioid endogenous pain inhibitory systems. The lack of change in
      sensitivity at some sites could indicate a competitive balance between excitatory
      and inhibitory mechanisms. The deep peroneal nerve specifically innervates both
      the TA muscle and the only site of hyperalgesia indicating spatial summation of
      afferent activity from these structures.

PMID- 12195524
TI  - Differential contribution of some cortical sites to the formation of memory
      traces supporting fear conditioning.
AB  - The aim of the present work was to assess the role of some cortical sites of the
      rat (the prefrontal, PFC, frontal, FC, parietal, PAC, and perirhinal, PC,
      cortices) in the acquisition of classical fear conditioning (CS and context
      conditioned freezing). Using the reversible ablation technique the sites were
      inactivated with lidocaine (LIDO), administered before the one-trial training
      session. The freezing response, taken as memorization index, was measured in
      conditions of full functional recovery after the short reversible LIDO
      inactivation either 3 h ("short-term" memory) and/or 72 h ("long-term" memory)
      later, so as to follow the temporal dimension of mnemonic elaboration. The
      results of the inactivations performed during the training session show that PFC,
      FC, PAC and PC play contemporaneous but distinct roles in the memorization of
      aversive responses to CS and context. PC inactivation weakened the retention of
      both mnemonic traces at the 3-h delay. At the same delay FC and PAC inactivation
      weakened only freezing to acoustic CS while PFC inactivation improved the
      retention of both traces. Inactivation of all four sites was followed by
      significant amnesia for both traces at the 72-h after-acquisition delay. The
      present findings show that PFC, FC, PAC and PC reversible inactivation during the
      acquisition training session diversely interferes with the memorization of
      conditioned freezing to acoustic CS and context. Moreover, the different results
      obtained at the two different retention intervals support the hypothesis that
      "short-term" and "long-term" memories are not necessarily linked, the earlier one
      not always influencing the subsequent one.

PMID- 12195525
TI  - Primary motor cortical neurons encode functional muscle synergies.
AB  - Many different kinematic and kinetic signals have been proposed as possible
      variables under the control of the primary motor cortex. Despite the presence of
      direct projections to motor neurons, muscle activation has received less
      attention as a controlled variable. Furthermore, although it is well known that
      descending fibers project to multiple motor pools, an objective, quantitative
      study of the relation between neuronal modulation and the activity of groups of
      muscles has not previously been reported. We have recorded the discharge of 310
      neurons located in the primary motor cortex of two monkeys, along with the
      activity of a variety of arm and hand muscles. Data were recorded while the
      monkey reached to and pressed a series of illuminated buttons. The similarity of
      a given neuron's discharge with respect to each muscle was determined by
      calculating the linear cross-correlation between its discharge rate and each
      rectified, filtered electromyogram. A "functional linkage vector" was then
      constructed, which expressed the similarity of that neuron's discharge to the
      entire set of muscles. We discovered discrete groups of functional linkage
      vectors within the high order muscle space for both monkeys which corresponded to
      functional properties of the neurons measured by other methods. Several of these
      groups appeared to represent a functional synergy of muscles, such as those
      required to extend the limb, press a button, or open the hand in preparation for
      the press. When the dimensionality of this space was reduced by a principal
      components analysis, the originally identified clusters of neurons remained well
      separated. These results are consistent with the hypothesis that the discharge of
      individual neurons in the primary motor cortex encodes the activity of a
      relatively small number of functionally relevant groups of muscles. It will be
      important to determine whether these results will also apply to more complex
      behavior, and to what extent these functional muscle synergy representations
      remain fixed across behaviors.

PMID- 12195526
TI  - Rehearsal by eye movement improves visuomotor performance in cerebellar patients.
AB  - In order to assess the effect of rehearsal by eye movement alone on visuomotor
      performance, the eye movements and visually guided stepping of two cerebellar
      patients were monitored before and after a first and second batch of eye-movement
      rehearsals, in which patients made saccadic eye movements to the first 6 footfall
      targets (in a sequence of 18) whilst standing stationary at the start of the
      walkway. There was a marked improvement in oculomotor and locomotor performance
      following the second batch of eye-movement rehearsal. Both patients showed
      reduced occurrence of saccadic dysmetria, evident as a significant increase in
      the proportion of single to multi-saccadic eye movements (from 46 to 77% for DB
      and from 75 to 94% for TP). This was accompanied by increased regularity and
      accuracy of stepping in both patients, and decreased stance and double support
      phase durations (one patient only). Separate testing confirmed that these
      improvements in eye movements and stepping did not result from simple repetition
      of the task. This is the first demonstration of a technique--rehearsal by eye
      movement--that improves the visuomotor performance of cerebellar patients. It is
      compelling evidence for our proposal that during visually guided stepping the
      locomotor control system is dependent on assistance from the oculomotor control
      system.

PMID- 12195527
TI  - Visual responses in the temporal cortex to moving objects with invariant
      contours.
AB  - We were interested in how the visual attributes of motion and shape are
      integrated in the temporal cortex of monkeys. We recorded neural activity in the
      middle portion of the superior temporal sulcus (STS) of monkeys during a
      sequential visual discrimination task while the animals maintained fixation. We
      used images of objects with invariant outlines rotating in 3D space either
      clockwise or counterclockwise as visual stimuli. In the sequential discrimination
      task, after the fixation pattern was presented for 1.0 s, the sample stimulus
      (S1) appeared at the center of the monitor screen for 0.8 s. After a delay period
      of 0.5-2.0 s, the same stimulus or a new response stimulus appeared on the screen
      for 0.8 s. In each block, the response stimulus was either a new direction of
      rotation or a new shape. Of 425 responding neurons isolated in the STS, 202 (48%)
      showed significant activity when S1 stimuli were presented. Of these visual
      neurons, 27 (13%) were categorized as motion and shape selective (MS), 69 (34%)
      as shape selective (S), and 6 (3%) as motion selective (M). Briefer than for MS
      or S neurons, the latency of the remaining non-selective neurons was 80 ms.
      Latencies of visual response (110 ms) of both MS and S neurons were similar. On
      the other hand, MS neurons started responding later (180 ms) to changes in
      direction. Our findings show that neurons in the STS, responding selectively to
      changes in shape, do respond to relatively simple motion and that variable
      contouring is not essential to elicit motion response. The results may also
      suggest the functional segregation of selective versus non-selective neurons and
      the later arrival of directional response to MS neurons in the STS.

PMID- 12195528
TI  - Development of gaze tracking of small and large objects.
AB  - A longitudinal study was designed to address the relationships between the smooth
      pursuit (SP) and the optokinetic response (OKR). Eye and head movements were
      measured in infants between 7 and 14 weeks of age. They were placed in front of a
      moving object subtending visual angles of 2.5, 5, 7, 14, 21, 28, and 35 degrees.
      The object oscillated sinusoidally along a horizontal path with a frequency of
      0.25 Hz and an amplitude of +/-25 degrees visual angle. It was found that the
      number of saccades was dependent on object size: at 6 and 9 weeks of age there
      were more saccades for the smallest objects. With increasing age, the number of
      saccades decreased. The composite eye movement gain (smooth tracking + saccades)
      did not change with age but for the 6.5-week group the gain was higher for
      smaller objects. The gain of the smooth eye tracking increased with age and
      showed no dependency on object size. In conclusion, the results do not support
      the concept of two separate systems, the OKR and the SP, each of them processing
      eye tracking of small and large objects. Finally, it was observed that two
      infants at 6.5 weeks of age who used considerable head movements did not inhibit
      the vestibular-ocular response.

PMID- 12195529
TI  - Tonic rhythmic activity of rat cerebellar neurons.
AB  - Simultaneous recordings of multiple single unit activity in both cerebral and
      cerebellar cortex, cortical EEG, and both nuchal and vibrissal EMG were obtained
      in nine unrestrained rats. Putative Purkinje cells of the deep vermal cerebellar
      cortex exhibited rhythmic discharge of simple spikes with extremely low
      variability in interspike intervals for several hours. The highly rhythmic nature
      of spike discharge was remarkably stable across all states of sleep (both slow
      wave and rapid eye movement sleep) and wake including quiet waking, grooming,
      eating, running in a familiar environment, and exploring a novel environment. The
      frequencies at which oscillatory discharges took place varied, among different
      cells, between 16 and 142 Hz; however, 75% of the recorded cells discharged at
      frequencies between 20 and 50 Hz. From recordings in which two to four such cells
      were recorded simultaneously, evidence was found for multiple cells firing at the
      same frequency as well as for multiple cells firing at different frequencies. The
      precise timing of spike discharge in these cells makes them potential candidates
      to participate in timing functions thought to depend on the cerebellum

PMID- 12195531
TI  - Lessons from the skeleton: was the Women's Health Initiative (WHI) a primary
      prevention trial?

PMID- 12195532
TI  - Mechanical strain and bone cell function: a review.

PMID- 12195533
TI  - Effects of gender and age on the association of apolipoprotein E epsilon4 with
      bone mineral density, bone turnover and the risk of fractures in older people.
AB  - The aim of this study was to examine whether the presence of apolipoprotein E
      epsilon4 (ApoE epsilon4) is associated with a lower bone mineral density (BMD),
      lower quantitative ultrasound (QUS) measurements, higher bone turnover and
      fracture risk, and whether these relations are modified by gender and age. A
      total of 1406 elderly men and women (> or =65 years) of the Longitudinal Aging
      Study Amsterdam (LASA) participated in this study. In all participants, QUS
      measurements were assessed, as well as serum osteocalcin (OC) and urine
      deoxypyridinolin (DPD/Cr urine). Follow-up of fractures was done each three
      months. In a subsample ( n = 604), total body bone mineral content (BMC) and BMD
      of the hip and lumbar spine were measured. In addition, prevalent vertebral
      deformities were identified on radiographs. In women, the presence of ApoE
      epsilon4 was associated with significantly lower femoral neck BMD (g/cm(2); mean
      +/- SEM; epsilon4+, 0.64 +/- 0.01 vs. epsilon4-, 0.67 +/- 0.01; p = 0.04), lower
      trochanter BMD (g/cm(2); mean +/- SEM; epsilon4+, 0.58 +/- 0.01 vs. epsilon4-,
      0.61 +/- 0.01; p = 0.01) and lower total body BMC (g; mean +/- SEM; epsilon4+,
      1787 +/- 40.0 vs. epsilon4-, 1863 +/- 23.8; p = 0.04). Women with ApoE epsilon4
      also had a higher risk of severe vertebral deformities (OR=2.78; 95%CI: 1.21
      6.34). In men, the associations between ApoE status and both hip BMD and QUS
      depended on age. Only among the younger men (65-69 years) was the presence of
      ApoE epsilon4 associated with lower BMD values. Bone markers and fractures were
      not associated with ApoE epsilon4 in either women, or men. In conclusion, this
      large community-based study confirms the importance of ApoE epsilon4 as a
      possible genetic risk factor related to BMD and vertebral deformities and
      demonstrates that its effect is gender related, and depends on age in men only.

PMID- 12195534
TI  - An association between respiratory function and bone mineral density in women
      from the general community: a cross sectional study.
AB  - Respiratory function has been associated with bone mineral density (BMD) in
      patients with respiratory diseases. We examined the relationship between bone
      density measured at the hip and respiratory function in women from the general
      community. A total of 4830 women aged 45-76 years were recruited from general
      practice age-sex registers in Cambridge between 1991 and 1995. At baseline
      survey, data collection included health questionnaires, measures of
      anthropometry, respiratory function, as well as bone mineral density BMD measured
      using dual energy X ray absorptiometry. BMD at total hip, femoral neck and
      trochanter significantly and positively correlated with FEV(1). This association
      was independent of age, weight, height, smoking habit, history of respiratory
      diseases, corticosteroids and use of hormone replacement therapy. After
      adjustment for these factors, an increase in FEV(1) of 1 l/s was associated with
      0.026, 0.021 and 0.026g/cm(2) increase in bone mineral density at total hip,
      femoral neck and trochanter respectively. The association was consistent and
      similar in magnitude among current smokers and current non-smokers and across all
      age groups. The magnitude of the association was comparable to that associated
      with an age difference of 6 years or weight difference of 5 kg. Women in the
      bottom compared to top quartile of respiratory function had about double the risk
      of low bone density independent of other factors. Respiratory function measured
      using FEV(1) is positively and independently related to BMD in these middle-aged
      and older women across the whole normal distribution of these physiologic
      measures. This may reflect underlying common determinants such as physical
      activity. Even in healthy women, respiratory function may be a marker for women
      at increased risk of osteoporosis and associated fractures.

PMID- 12195535
TI  - Embryo/fetus radiation dose and risk from dual X-ray absorptiometry examinations.
AB  - The aim of the current study was to estimate the embryo/fetus radiation doses and
      risks associated with spinal and hip dual X-ray absorptiometry (DXA) scans
      performed on the pregnant mother. The results were compared with the embryo/fetus
      dose from a thoracolumbar radiograph and pelvic radiograph. Posteroanterior (PA)
      lumbar spine and proximal femur scans during the first, second and third
      trimesters were performed on a phantom simulating pregnancy at the three
      trimesters of gestation. All scans were carried out using a Hologic 1000/W pencil
      beam DXA unit. Moreover, embryo/fetus doses from a (a) thoracolumbar radiograph
      and (b) pelvic radiograph were estimated for all periods of gestation using the
      same phantom. Radiation doses were measured using thermoluminescent dosimeters.
      The dose reduction achievable by shielding the embryo/fetus with a protective
      apron during DXA scans was studied for all trimesters of gestation. The
      embryo/fetus doses during the first trimester were measured to be 1.7 mGy and 2.7
      mGy for the PA spine and femur DXA scan, respectively, for an embryo/fetus
      located 8.5 cm from the anterior maternal surface. The risk of excess fatal
      cancer was 0.2 per million unborn children irradiated in utero for measurements
      of the spine and 0.3 per million unborn children for measurements of the femur.
      The embryo/fetus doses during the second and third trimesters were 2.7 mGy and
      4.9 mGy respectively for the scans of the lumbar spine. The risk of childhood
      fatal cancer was 0.3 per million for the second trimester and 0.5 per million for
      the third trimester. The embryo/fetus radiation doses during the second and third
      trimesters were estimated as 1.4 mGy and 1.0 mGy respectively for the
      examinations of the proximal femur. The risk of childhood fatal cancer was 0.1
      per million for both trimesters. The use of the apron resulted in a very small
      change in the dose absorbed by the embryo/fetus. The embryo/fetus dose associated
      with both DXA modes investigated in the current study is at least 700 times lower
      in comparison with embryo/fetus dose from a thoracolumbar or pelvic radiograph in
      all periods of gestation. In conclusion, the embryo/fetus dose in bone density
      measurements of spine and femur using pencil beam DXA is lower than the average
      daily natural background in the United States of 8 mGy. The health provider can
      decide whether a DXA scanning is beneficial to a pregnant woman, taking into
      account the potential radiation risks to the embryo/fetus presented in the
      current study.

PMID- 12195536
TI  - Prevalence of vertebral deformity and its associations with physical impairment
      among Japanese women: The Hizen-Oshima Study.
AB  - Vertebral fractures are a hallmark of postmenopausal osteoporosis and an
      important end point in trials of osteoporosis treatment, but the clinical
      significance of vertebral deformities remains uncertain. We examined the
      prevalence of vertebral deformity and associations of vertebral deformities and
      other characteristics with physical functioning among 584 Japanese women ages 40
      to 89 years. Lateral spine radiographs were obtained and radiographic vertebral
      deformities were assessed by quantitative morphometry, defined as vertebral
      heights more than 3 SD below the normal mean. A self-administered questionnaire
      was used to survey participants about difficulty in performing selected basic and
      instrumental activities of daily living (ADL). Overall, 15% of women had at least
      one vertebral deformity, and 8% had 2 or more. The prevalence of vertebral
      deformities increased progressively with age. Half of women ages 80 and over had
      vertebral deformities. Impaired function was defined as difficulty performing 3
      or more ADLs. After adjusting for age, the odds of impaired function were
      increased by 1.4 times (95% CI: 0.7, 2.9) in women with a single vertebral
      deformity, and 3.1 times (1.4, 6.8) in those with two or more deformities.
      Additional adjustment for number of painful joints, number of comorbidities, body
      mass index, and back pain did not materially alter these findings. In conclusion,
      women with multiple vertebral deformities had significantly greater impaired
      function. The association was independent of age, back pain and the number of
      painful joints, suggesting that deformities may impair function even when back
      pain is not present.

PMID- 12195537
TI  - Survival and potential years of life lost after hip fracture in men and age
      matched women.
AB  - Hip fracture is associated with a higher mortality rate in men than in women.
      However, mean age of men and women with hip fracture differs markedly. Thus, some
      of the differences in the clinical pattern and outcome between genders could be
      related to different ages. To avoid the influence of age on gender-specific
      outcome, we analyzed prefracture conditions and hip fracture outcome in a cohort
      of men and of age-matched women. Risk factors for low bone mass were recorded in
      106 men (mean age +/- SD, 80.3 +/- 9.3 years) and 264 age-matched women (mean age
      81.4 +/- 8.0) with hip fracture. We compared mortality rate, survival, years of
      potential life lost and modification of housing conditions. These outcomes were
      prospectively assessed during an average 3.6 years follow-up (up to 7 years). Men
      with hip fracture differed from age-matched hip-fractured women by a higher
      alcohol and tobacco consumption, a greater frequency of living in couple, and by
      less prevalent fractures. Mortality rate after hip fracture was significantly
      higher in men (RR = 1.74, 95% CI 1.34-2.24). Since mortality is higher in the
      general male population, we compared reduction in life expectancy taking into
      account the gender-specific mortality rate. The excess mortality in each age
      group of hip-fractured patients, which was measured during the whole follow-up
      period, and is an estimate of death attributable to fracture, did not differ
      between genders. Reduction in life expectancy due to hip fracture was similar in
      both genders (5.9 +/- 4.5 and 5.8 +/- 4.8 years, in men and women, respectively;
      NS), but the proportion of the years of life lost was higher in men (70 +/- 33%)
      than in women (59 +/- 42%, p < 0.01). It was concluded that for the same age,
      mortality rate after hip fracture was higher in men than in women. Although the
      reduction in life expectancy was similar in both genders, the proportion of the
      years of life lost was higher in men, suggesting a worse impact of hip fracture
      on survival in men, even after consideration of the higher mortality rate in the
      general male population.

PMID- 12195538
TI  - Does follow-up of osteoporotic women treated with antiresorptive therapies
      improve effectiveness?
AB  - The use of biochemical markers of bone turnover has been advocated to improve
      follow-up of women receiving antiresorptive therapies for osteoporosis, but this
      strategy is not yet supported by trials showing it improves effectiveness of
      treatments. To explore the potential value of markers of bone turnover to monitor
      antiresorptive treatments of osteoporosis, we conducted a decision analysis using
      a decision tree and Markov modeling. We have compared two strategies: treatment
      of a woman without specific monitoring; and treatment of this woman with
      measurement of a serum marker of bone resorption after 3 months of treatment,
      with change of treatment if response to treatment assessed by this marker was not
      satisfactory. The base case is the treatment of a 60-year-old osteoporotic woman
      with a total hip T-score of -3, using a second generation bisphosphonate during 5
      years. We found that follow-up produced slightly greater quality adjusted life
      years (QALYs) than no follow-up (8.1560 vs 8.1532, i.e. a one day difference). In
      a two-way sensitivity analysis, the follow-up option produced higher QALYs so
      long as adherence rate with follow-up was equal or superior to the proportion of
      women who adhered without follow-up. For example, if the proportion of women
      adherent to treatment was increased from 50% to 60% by follow-up, then the
      expected value of the follow-up branch was increased from 8.1560 QALYs to 8.1800
      QALYs (i.e. a difference of 9 days). In addition, the higher the non-response
      rate, the greater the benefit from monitoring with a biochemical marker. In
      conclusion, our decision analysis model suggests that follow-up of osteoporotic
      women treated with a second generation bisphosphonate during a 5-year period
      using an early measurement of a serum marker of bone resorption may increase
      effectiveness of the treatment on quality of life, but the effect is very small.
      So, the use of follow-up measures of bone turnover may be based on patient and
      physician preferences.

PMID- 12195539
TI  - Linkage and association for bone mineral density and heel ultrasound measurements
      with a simple tandem repeat polymorphism near the osteocalcin gene in female
      dizygotic twins.
AB  - In this confirmatory candidate gene study, we investigated possible linkage and
      association for bone density, heel ultrasound and bone turnover with the
      osteocalcin gene using the nearby (50-180kb) microsatellite marker D1S3737. Non
      identical twin sisters aged 18-75 years at first interview were recruited for the
      study from the St Thomas' UK Adult Twin Registry with 1366 women being genotyped
      for marker D1S3737. Linkage, allelic association and joint linkage and
      association tests were carried out using quantitative transmission disequilibrium
      tests (QTDT), along with post-hoc multivariate tests of linkage and association.
      Phenotypes tested were bone mineral density (BMD) at the spine, left forearm and
      left total hip; quantitative ultrasound measurements of the heel including
      velocity of ultrasound (VOS) and broadband ultrasound attenuation (BUA); and bone
      turnover markers, urine deoxypyridinoline (DPD), serum osteocalcin, bone specific
      and total alkaline phosphatase (ALP). BMD and ultrasound variables showed
      evidence of pleiotropic linkage ( p = 0.05) and association ( p = 0.02) with the
      marker in postmenopausal women. Bone markers showed little or no evidence of
      linkage and association for any age group. Evidence for pleiotropic linkage
      appeared to be strongest for BUA and spine BMD in postmenopausal women. The
      univariate test statistic for BUA was chi(2)(1)=12.8 ( p = 0.0003), equivalent to
      a LOD score of 2.8. DPD showed borderline evidence of linkage to the marker for
      women of all ages. Multivariate model-fitting showed allele 10 to be negatively
      associated with BMD, VOS and BUA via a common pathway, suggesting the putative
      functional polymorphism affects both bone content and structure through shared
      underlying metabolic pathways. It is likely that the alleles are in linkage
      disequilibrium with functional polymorphism(s) in or nearby the osteocalcin gene,
      which may contribute to the onset of osteoporosis.

PMID- 12195540
TI  - FDG-PET findings of vertebral compression fractures in osteoporosis: preliminary
      results.
AB  - The aim of this study was to evaluate FDG-PET findings in patients with
      osteoporosis or preclinical osteoporosis and acute vertebral compression
      fractures in order to determine whether FDG-PET has a value for distinction of
      pathological from osteoporotic vertebral fractures. 17 patients with a
      spontaneous compression fracture of the spine were evaluated by bone scanning
      with Tc-99m HDP, positron emission tomography with fluorine-18 deoxyglucose (FDG
      PET) and magnetic resonance imaging (MRI). Osteoporosis had been established in
      all cases by X-ray and osteodensitometry. PET and bone scan images were scored
      independently from 0 (no pathological uptake) to 4 (definitive pathological
      uptake) by two blinded nuclear medicine physicians. The results of the blinded
      scoring were compared to MRI findings which served as gold standard. In 13 out of
      17 patients, MRI demonstrated a vertebral fracture generating from osteoporosis.
      In 12 of these 13 cases, PET scans were scored with 0 or 1 and categorized as
      true negative. Standard uptake values (SUV) ranged between 1.1 and 2.4. In one of
      the 13 patients, PET was interpreted false positive with an uptake score of 3
      (SUV = 2.9). Of the 17 patients, MRI revealed a pathological fracture caused by
      spondylodiscitis in three patients and by plasmacytoma in one patient. In these
      patients, all PET scans were highly positive with a score of 3 and 4 and SUV
      values between 3.8 to 9.8. The bone scans of all 17 patients were positive with
      scores of 3 or 4 but a differentiation between osteoporotic and pathological
      fractures was not possible. Our preliminary results indicate that acute vertebral
      fractures that originated from osteoporosis or preclinical osteoporosis tend to
      have no pathologically increased FDG uptake. Since a high FDG uptake is
      characteristic for malignant and inflammatory processes, use of FDG-PET may have
      potential value for differentiation between osteoporotic and pathological
      vertebral fractures.

PMID- 12195542
TI  - Patients' needs during the year after a suicide attempt. A secondary analysis of
      a randomised controlled intervention study.
AB  - OBJECTIVE: We first studied whether changes of needs were influenced by randomly
      allocated telephone interventions between 1 and 12 months after a suicide attempt
      in addition to treatment as usual. These were aimed at improving motivation for
      professional treatment. As a secondary analysis we investigated the frequency and
      changes of needs during this period and if changes were related to other outcome
      measures. METHOD: One month after a suicide attempt 216 patients were randomised
      to two telephone interventions or to no such interventions within 1 year. The
      Camberwell Assessment of Need (CAN) was used to evaluate 22 different need areas
      at 1 and 12 months. Other outcome measurements used were Global functioning axis
      V (GAF), psychological symptoms (SCL-90, GSI) and scale of suicide ideation
      (SSI). RESULTS: Of 178 patients who were followed up, 140 had been rated by CAN
      at both 1 and 12 months. Changes of needs did not differ between the randomised
      groups. At 1 month the patients had a mean number of 5.1 +/- 2.4 needs and 2.4 +/
      1.5 of these were considered as unmet. The most frequently reported needs
      concerned health aspects, basic needs and social needs. At 12 months needs
      concerning health aspects were significantly reduced, while basic needs and
      social needs were not. Changes of GAF explained 21 % and changes of GSI 4 % of
      the variance of the reduction of needs. CONCLUSIONS: After 12 months, needs in
      health aspects, basic needs and social needs were still common. A structured
      evaluation of the patient's needs seems to be helpful when planning treatment
      after a suicide attempt.

PMID- 12195541
TI  - Thinking life is not worth living. A population survey of Great Britain.
AB  - BACKGROUND: "Saving lives: our healthier nation" includes a target to reduce the
      death rate from suicide. Thoughts of suicide and feeling life is not worth living
      might be the first step in a pathway that can end in completed suicide. This
      study aims to identify factors associated with feeling life is not worth living
      amongst the household population of Great Britain, and to assess the strength of
      these associations after taking account of an individual's level of psychiatric
      morbidity. METHODS: The 1993 OPCS National Psychiatric Morbidity Surveys of Great
      Britain assessed psychiatric morbidity using the Revised Clinical Interview
      Schedule amongst a stratified, clustered probability sample of 9830 subjects
      representative of the British private household population aged 16-64. RESULTS:
      Of the sample 0.8 % (95 % CI 0.6 %-1 %) had thoughts of suicide in the week
      before interview and 3.1 % (95 % CI 2.7 %-3.5 %) reported thoughts of life not
      worth living in the week before interview. Psychiatric morbidity was most
      strongly associated with such thoughts. Ethnicity, marital status and low social
      support were strongly associated with such thoughts after adjusting for age, sex
      and psychiatric morbidity. CONCLUSIONS: Reducing psychiatric morbidity in the
      population as a whole might also decrease the frequency of suicidal thoughts.
      Policies which improve social support at a population level might also have a
      large impact on prevalence of suicidal thoughts.

PMID- 12195543
TI  - Expressed emotion in the client-professional caregiver dyad: are symptoms, coping
      strategies and personality related?
AB  - OBJECTIVE: The aim of this study was to investigate whether the characteristics
      of residents and professional caregivers are associated with the professionals'
      expressed emotion (EE). METHOD: Fifty-six residents in sheltered living who
      suffer from schizophrenia or a related psychotic disorder and their professional
      caregivers were enlisted. Standardised validated instruments were used to measure
      EE, the residents' social functioning, symptoms and social network size, and the
      professional caregivers' coping strategies and personality. RESULTS: There was
      strong evidence that high EE was associated with the residents' age, poorer
      social functioning and smaller network sizes. There was no significant
      relationship between EE and the residents' symptoms except for excitement.
      Concerning the professional caregivers, high EE professionals were less open than
      their low EE colleagues and had a lower education level. CONCLUSION: The
      residents' social functioning is an important correlate of the EE index.

PMID- 12195544
TI  - Gender and age-specific first incidence of DSM-III-R psychiatric disorders in the
      general population. Results from the Netherlands Mental Health Survey and
      Incidence Study (NEMESIS).
AB  - BACKGROUND: Prospective studies in the general population are needed to identify
      risk factors for mental disorders. Samples of sufficient size are needed, but
      large-scale studies that assess the incidence of psychopathology are rare. AIMS:
      The aim of this study was to investigate the 12-month first incidence rates (IR)
      by age and gender for 15 specified DSM-III-R disorders in the general population.
      Methods The study was based on a representative sample (N = 5618) of the Dutch
      population aged 18-64. RESULTS: The IR for any disorder was 5.68 per 100 person
      years at risk (men 4.45, women 6.94). IRs for both men and women were highest in
      the youngest age category. The most common 12-month incident disorders in men
      were alcohol abuse (IR = 4.09) and major depression (1.72). In women, the most
      common incident disorders were major depression (IR = 3.90) and simple phobia
      (3.17). CONCLUSIONS: The results show the rarity of first-onset of mental
      disorders. IRs vary strongly between the different life phases, as well as
      between men and women. This suggests potential target areas for age-specific and
      gender-specific prevention.

PMID- 12195545
TI  - The relationship between mental disorders and medical service utilization in a
      representative community sample.
AB  - BACKGROUND: Frequent use of health services has been associated with mental
      disorders and psychological distress. The present study aimed to determine how
      mental disorders affect the likelihood of using health services in a nationally
      representative sample. METHOD: The analysis was based on data on 3726 respondents
      aged 18-65 years from the German National Health Interview and Examination
      Survey, a nationally representative multistage probability survey conducted from
      1997 to 1999. Health care utilization in the previous year was measured by a self
      report questionnaire. Psychiatric diagnoses were assessed by a modified version
      of the Composite International Diagnostic Interview. RESULTS: The relationship
      between mental illness and medical service utilization was substantial and
      significant. Twelve-month prevalence rates for respondents with normal health
      service use were 10.2 % (affective disorders), 11.9 % (anxiety disorders), 8.9 %
      (somatoform disorders), and 15.4 % (substance use disorder). In contrast, 12
      month prevalence rates for high utilizers were 25.1 % (affective disorders), 29.3
      % (anxiety disorders), 22.2 % (somatoform disorders), and 17.1 % (substance use
      disorder). CONCLUSIONS: High utilizers of health care service should be assessed
      for common mental disorders. Efforts should be made to increase awareness,
      recognition, and appropriate early intervention of mental disorders.

PMID- 12195546
TI  - Do long-term hospitalised patients benefit from discharge into the community?
AB  - OBJECTIVE: The study investigated whether long-stay patients would benefit from
      discharge into the community in Berlin, Germany. METHOD: In a prospective
      controlled study, all long-term hospitalised psychiatric patients from a defined
      catchment area were assessed using established standardised instruments. Quality
      of life, treatment satisfaction, needs and psychopathology were re-assessed in 63
      non-discharged patients 1.5 years later, and in 65 resettled patients 1 year
      after discharge. RESULTS: Discharged patients were younger and had spent less
      time in psychiatric hospitalisation. Whilst patients who remained in hospital
      care did not show significant changes over time, discharged patients did. Changes
      in subjective quality of life and total number of needs - but not in
      psychopathology, unmet needs, and treatment satisfaction - were significantly
      more favourable in resettled patients as compared to the control group.
      CONCLUSION: The findings are in line with other studies and suggest that long
      stay patients can benefit from discharge into the community, particularly with
      respect to their quality of life. Positive changes in the process of
      deinstitutionalisation seem not dependent on the specific national context, and
      also apply to younger patients who have not yet spent 10 or more years in
      psychiatric hospitals.

PMID- 12195547
TI  - Iatrogenic depression in the elderly. Results from a community-based study in the
      Netherlands.
AB  - BACKGROUND: The aim of this study was to investigate the association between the
      use of medication and depression in the elderly. METHOD: A cross-sectional
      population-based study was conducted. Associations between the use of medication
      and depression are corrected for eight other etiological correlates of
      depression. The sample consisted of 2646 elderly people living in 11
      municipalities in the Netherlands. Subjects were taken from the Longitudinal
      Aging Study Amsterdam, a 10-year longitudinal study on predictors and
      consequences of changes in well-being and autonomy in the older population.
      Associations are expressed in odds ratios (95 % Confidence Intervals) between the
      use of (groups of) medication and depression. Results are adjusted for age, sex,
      urbanicity, socioeconomic status, physical health, social and interpersonal
      support, comorbidity with other psychiatric disease and personality. The
      Population Attributable Risk percentage was calculated for selected groups of
      medication. RESULTS: After correction for competing risk factors of depression,
      22 individual medications and nine groups of medications had unique associations
      with depression. CONCLUSIONS: The use of depressogenic medication is an
      independent etiological factor in the pathogenesis of depression.

PMID- 12195549
TI  - A woman's perspective in a man's field.

PMID- 12195550
TI  - Silver Book 2002. Update to 2002 Buyer's Guide, new companies, EMS statistics.

PMID- 12195551
TI  - Front-line leadership. Chapter 2: Damage control.

PMID- 12195552
TI  - [Plan for controlling multi-drug resistant Staphylococcus aureus: resistance
      status becomes ever more problematic. "Hygiene in ambulatory and inpatient
      nursing and geriatric care/rehabilitation of the German Society of Hospital
      Hygiene].

PMID- 12195553
TI  - [Emergency aid in Afghanistan: in search for lost life time (interview by Katrin
      Balzer)].

PMID- 12195554
TI  - [Radiofrequency thermo-ablation in primary and secondary liver neoplasms].

PMID- 12195555
TI  - Polymorphous light eruption.
AB  - Polymorphous light eruption (PLE) is a common idiopathic photosensitivity
      disorder with an estimated prevalence of 10-20%. It is characterized by an
      intermittent skin reaction to ultraviolet (UV) radiation exposure, consisting of
      non-scarring pruritic erythematous papules, vesicles or plaques that develop on
      light-exposed skin. Despite the different morphology in different individuals,
      the eruption tends to have a monomorphous presentation in any single subject. The
      histopathological features of PLE are distinct and comprise a perivascular
      lymphocytic infiltrate in the dermis, subepidermal oedema and variable epidermal
      changes. The pathogenesis of PLE is not well known, but findings suggest that it
      is a delayed-type hypersensitivity reaction to one or more UV-modified cutaneous
      antigens. The principal action of PLE is mainly in the UVA region, although some
      subjects exhibit sensitivity to UVB alone or to both UVA and UVB radiation at the
      same time. Preventive measures in PLE include the regular use of photoprotective
      methods combined with graduated exposures to natural sunlight. The induction of
      immune tolerance by phototherapy and photochemotherapy are useful prophylactic
      methods in moderate to severe cases. The role of systemic agents in the
      management of PLE is under investigation. This article reviews the
      epidemiological, pathogenetic and clinical aspects of PLE and discusses recent
      advances in the diagnostic approach and management of this condition.

PMID- 12195556
TI  - The skin and the catastrophes.

PMID- 12195557
TI  - Unusual employ of laser in dermatology: to know, to be able to do, to be.

PMID- 12195558
TI  - Schnitzler's syndrome: what's new?

PMID- 12195559
TI  - Cockayne syndrome, between transcription and DNA repair defects.

PMID- 12195560
TI  - Photodynamic therapy: when and why?

PMID- 12195561
TI  - Terbinafine: efficacy and tolerability in young children with tinea capitis due
      to Microsporum canis.
AB  - AIMS: We carried out an open, prospective, uncontrolled study to evaluate the
      efficacy and tolerability of terbinafine in the treatment of young children with
      tinea capitis due to Microsporum canis. METHODS: A total of 83 healthy,
      immunocompetent children (age range 2-13 years) were enrolled in eight centres in
      Estonia, Latvia and Lithuania. Patients received oral terbinafine in dosages
      based on weight, 62.5 mg for those weighing 10-20 kg, 125 mg for 20-40 kg, plus
      application of topical 1% terbinafine cream twice daily to affected areas.
      Treatment lasted for 4 weeks, followed by an 8-week observation (treatment-free)
      period. All the subjects were assessed for efficacy and tolerability at 12 weeks.
      RESULTS: Eighty-one subjects were available for assessment at 12 weeks: 32 had
      completely recovered, with no evidence of relapse during the observation period,
      and 21 showed mycological cure, but presented residual physical signs of
      infection. Thus the effective cure rate was 65.4% in an infection known to be
      more difficult to cure than other causes of tinea capitis. Terbinafine was well
      tolerated by these children. CONCLUSIONS: This study showed effective cure of two
      thirds of 81 cases of tinea capitis caused by M. canis with a 4-week course of
      treatment. As one-third of the cases did not respond to treatment, we suggest
      using combined oral and topical treatment with terbinafine in children with tinea
      capitis caused by M. canis.

PMID- 12195562
TI  - Human papillomavirus molecular biology and pathogenesis.
AB  - Human papillomavirus (HPV) infection is the most common sexually transmitted
      disease in the world and accounts for an estimated 11% of the global cancer
      incidence in women. HPV-16 is the most prevalent type detected in cervical cancer
      and along with types 18, 31, 33 and 45 has been classified as a class I
      carcinogen. In addition to cervical cancer, HPVs are also associated with the
      malignant transformation of other mucosal and skin cancers. Thus, the combination
      of the malignant potential of HPV and its high prevalence of infection confers to
      it an importance of generalized clinical and virological significance. The
      natural history of HPV infection with or without treatment varies from
      spontaneous regression to persistence. The most important mechanism for wart
      regression appears to be cell-mediated immunity. Cytokines released by
      keratinocytes or cells of the immune system may play a part in the induction of
      an effective immune response against HPV infection and the subsequent regression
      of lesions. This review discusses the molecular biology, pathogenesis and
      immunology of HPV infections.

PMID- 12195563
TI  - The Koebner phenomenon: review of the literature.
AB  - First described in 1877 as the appearance of psoriatic lesions in the uninvolved
      skin of psoriatic patients as a consequence of trauma, the Koebner phenomenon has
      since been described in numerous diseases. Other authors have tried to implicate
      either infections or parasitic causes as the pathogenesis of this phenomenon.
      Subsequent research by many authors have contributed to our poor understanding of
      this reaction in the hope of understanding the pathogensis of psoriasis. We
      present a review of the literature covering the following topics as they relate
      to the Koebner phenomenon: diseases that koebnerize and their possible causes,
      predisposing and provoking factors, type, site, depth and degree of trauma, the
      all or none phenomenon, time lag, site preference, medications, inhibition of
      koebnerization and reverse koebnerization.

PMID- 12195564
TI  - The effects of 17 August Marmara earthquake on patient admittances to our
      dermatology department.
AB  - On 17 August 1999 a devastating earthquake with a magnitude of 7.4 on the Richter
      scale occurred in Marmara region of Turkey and the epicentre of the earthquake
      was our city. In this study we aimed to determine the influence of a major
      earthquake on patient admittance's to the outpatient clinic of our dematology
      department. All the registrations of the outpatient clinic of our dermatology
      department in a period of 6 months after the earthquake and the same period last
      year were revised retrospectively and categorized into 15 subgroups. The first 3
      months registrations (earthquake group 1) and the second 3 months registrations
      (earthquake group 2) after the earthquake were compared with those of the same
      periods in last year, respectively (control group 1 and control group 2). Also
      the earthquake group 1 was compared with the earthquake group 2. When the results
      were evaluated, it was seen that the incidence of infections-infestations was
      significantly higher in the earthquake group 1 when compared with the control
      group 1. When the earthquake group 2 and the control group 2 were compared with
      each other regarding the incidences of the skin diseases, no statistically
      significant difference was found. The incidences of erythematous-squamous skin
      diseases, pruritus and neurocutaneous dermatoses and eczemas were significantly
      higher in the earthquake group 2 when compared with the earthquake group 1. On
      the other hand, the incidences of infections-infestations and dermatoses due to
      physical factors were significantly lower in the earthquake group 2 when compared
      with the earthquake group 1. We think that the alteration in the admittance's to
      outpatient clinic of our dermatology department in the first 3 months after the
      earthquake is due to the damaged infrastructures and unhygienic life conditions
      and in the second 3 months is due to psychoemotional factors related to
      earthquake.

PMID- 12195565
TI  - Chronic prostatitis and chronic pelvic pain in men: aetiology, diagnosis and
      management.
AB  - Patients with chronic prostatitis/pelvic pain syndrome typically report genital
      or pelvic pain (in or around the penis, perineum, scrotum) lasting > 3 months.
      Whereas true chronic bacterial prostatitis is an uncommon condition characterised
      by recurrent prostatic and urinary infection, chronic pelvic pain syndrome (CPPS)
      is a common condition in which no infection is found. Recent surveys suggest a
      prevalence of 2.5-3% for CPPS. The four-glass test, traditionally used to
      distinguish inflammatory and inflammatory forms of CPPS, has not been adequately
      validated; whether the distinction is clinically meaningful is increasingly
      questioned. The aetiology of CPPS is not known; urodynamic studies imply a
      neuromuscular origin. More recent work supports a role for proinflammatory
      cytokines in the pathogenesis. In the management of chronic bacterial
      prostatitis, trials support the use of quinolone antibiotics as first-line
      treatment. In contrast, the management of CPPS is generally unsatisfactory, as no
      reliable treatment has been identified. Treatments commonly tried include
      antibiotics (notably tetracyclines, quinolones and macrolides), anti-inflammatory
      agents, and alpha blockers. Newer approaches include trials of finasteride,
      quercetin and rofecoxib. A recent systematic review demonstrated that none of the
      current diagnostic and treatment methods for CPPS is supported by a robust
      evidence base.

PMID- 12195566
TI  - Seasonality trends of Pediculosis capitis and Phthirus pubis in a young adult
      population: follow-up of 20 years.
AB  - BACKGROUND: It is not mandatory to report Pediculosis capitis and Phthirus pubis
      in most countries; therefore, little is known about the seasonality of these
      infestations. METHODS: We analysed the data based on routine and mandatory
      reporting of every case of Pediculosis capitis and Phthirus pubis to the Army
      Health Branch Epidemiology Department, Israel, over the last two decades.
      RESULTS: The average 20-year incidence of Pediculosis capitis shows a significant
      rise during the warmer months (R2 = 0.692, P < 0.05) with a parallel significant
      decrease in the cooler months (R2 = 0.893, P < 0.05). The results for Phthirus
      pubis show a significantly higher person-time incidence in the winter (P <
      0.001). Sensitivity analysis to investigate possible sources of heterogeneity
      during this time indicated that no single year was an important source of
      heterogeneity. CONCLUSIONS: Pediculosis capitis is more frequent in the warmer
      months, whereas Phthirus pubis is more dominant in the cooler months.

PMID- 12195567
TI  - Alternative treatment of psoriasis with balneotherapy using Leopoldine spa water.
AB  - BACKGROUND: Leopoldine spa water is a hypotonic water rich in sulphate that has
      been used occasionally for balneological treatments in psoriatics. We evaluated
      the anti-inflammatory effects of this salso-sulphate water on the skin of
      subjects with psoriasis. PATIENTS AND METHODS: We selected 10 volunteer subjects
      (23-58 years old), who presented symmetrical, bilateral psoriasis involving at
      least 40% of the body surface. All the subjects were subjected to the following
      treatment schedule: (i) immersion of both arms in water twice a day [the right
      arm was immersed in Leopoldine spa water at its natural source temperature (27.2
      degrees C) for 30 min, and the left arm was immersed in double-distilled water
      for 30 min at a constant temperature of 27 degrees C]; (ii) both arms were
      exposed to the sun for 60 min after each immersion; and (iii) vaseline containing
      moisturizing creams were applied liberally. The treatment was continued for 4
      weeks and was well tolerated by all subjects. Response to treatment was assessed
      by means of the modified Psoriasis Area and Severity Index (PASI). Six of the 10
      subjects volunteered to undergo a cutaneous biopsy of lesional skin both before
      and 4 weeks after treatment to allow for assessment of modifications of the
      cutaneous infiltrate in the areas treated. RESULTS: At the end of 4 weeks the
      average pretreatment PASI score of the left arms was 5.72 (range 4-9.6) while the
      right arms had a mean PASI of 5.56 (range of 3.2-9). At the end of the study the
      average PASI score was 0.78 for the arms treated with Leopoldine spa water and
      2.83 for the arms treated with double-distilled water. The mean PASI improvement
      score for the Leopoldine spa water treated arms was 85.9% while the double
      distilled water treated arms showed a PASI improvement score of 50.5%. An
      immunohistological study showed significant differences between the cutaneous
      samples taken 4 weeks after treatment and those taken before treatment with
      Leopoldine spa water. There were significant decreases in the numbers of
      epidermal CD4+ and CD8+ T lymphocytes and CD1a+ Langerhans cells (microscopic
      field at x 22 objective), as well as a decrease in the epidermal keratinocyte
      expression of intercellular adhesion molecule-1 and interleukin-8 and the dermal
      expression of CD4+ and CD8+ T lymphocytes. CONCLUSIONS: These data show the
      potential anti-inflammatory effects of Leopoldine mineral waters on human skin
      affected by psoriasis.

PMID- 12195568
TI  - Inhibitory effects of Leopoldine spa water on inflammation caused by sodium
      lauryl sulphate.
AB  - BACKGROUND: Sulphur mineral waters may have anti-inflammatory effects on human
      skin. We evaluated the anti-inflammatory effects of Leopoldine spa water, a salso
      sulphate water (Table 1), on human skin tested with sodium lauryl sulphate (SLS).
      PATIENTS AND METHODS: Ten healthy, Caucasian volunteers 28-53 years old were
      enrolled in this study. SLS was tested on the right arm, in two concentrations
      (0.5% and 1%) dissolved in both double-distilled nonpyrogenic water and
      Leopoldine spa water in four separate test tubes; 0.02 mL of each solution was
      applied via the testing apparatus (Vand der Bend chambers, four squares measuring
      1 x 1 cm), which was fixed and remained in contact with the skin surface. The
      anti-inflammatory effect was measured via the variations of redness (chromometry,
      parameter a*), using a Minolta CR 200 chromometer. RESULTS: At base condition the
      values of a* of the areas that were tested ranged from 7.11 to 9.30 with a mean
      of 7.97. In regard to the reaction caused by SLS dissolved in double-distilled
      water, the values of a* ranged from 8.98 to 9.53, mean 9.24, for 0.5% SLS and
      from 12.81 to 14.33, mean 13.59, for 1% SLS. The a* values for the cutaneous
      reaction caused by SLS dissolved in Leopoldine spa water ranged from 7.22 to 9.60
      (mean 8.20) for 0.5% SLS and from 10.8 to 12.36 (mean 11.68) for the 1% SLS.
      CONCLUSIONS: These data show the potential anti-inflammatory effects of
      Leopoldine mineral water on human skin affected by modest inflammatory reactions
      caused by the direct application of the chemical irritant SLS. Leopoldine spa
      water can, thus, be considered a natural therapeutic alternative for the
      treatment of inflammatory skin conditions.

PMID- 12195569
TI  - Schnitzler's syndrome with monoclonal IgG kappa gammopathy: good response to
      cyclosporin.
AB  - Schnitzler's syndrome (SS) is a rare entity characterized by the association of
      chronic urticaria and monoclonal IgM gammopathy. Usually, intermittent fever,
      arthralgia and elevation of erythrocyte sedimentation rate also occur. We report
      a patient with the same symptoms, but with monoclonal IgG instead of IgM
      paraproteinaemia. Histological examination of the urticarial lesions showed signs
      of leucocytoclastic vasculitis. After 20 years of therapeutic failure,
      cyclosporin has achieved a total clearance of urticarial lesions in our patient.
      Two previous similar cases with clinical features of SS and monoclonal IgG
      immunoglobulin have been described. We suggest our case also represents a variant
      of SS with IgG gammopathy.

PMID- 12195570
TI  - Gemcitabine-induced erysipeloid skin lesions in a patient with malignant
      mesothelioma.
AB  - Gemcitabine is a nucleoside analogue that has shown to have antineoplastic
      activity in different solid tumours (lung, pancreas, bladder, colon, ovarian, and
      breast cancer) and malignant mesothelioma. The toxic effects of gemcitabine
      include myelosuppression, flu-like syndrome, altered liver function tests,
      bronchospasm, rash, itching, and fever. However, gemcitabine-induced erysipeloid
      skin reaction was reported in a small number of patients with previous history of
      radiotherapy or lymphedema. We reported a male patient who developed erysipeloid
      skin reaction following gemcitabine treatment in the absence of radiotherapy and
      lymphedema.

PMID- 12195571
TI  - Successful treatment of chromomycosis using carbon dioxide laser associated with
      topical heat applications.
AB  - A 59-year-old Japanese man presented with a slightly elevated, pruritic,
      erythematous plaque on his left buttock measuring 5 x 5 cm in diameter. The man
      had a history of chromomycosis, dating 6 years prior to the current consultation,
      for which he had been treated with oral terbinafine. Diagnosis of a recurrence of
      chromomycosis of the skin due to infection by Foncecaea pedrosoi was made after
      careful analysis of the clinical features, skin biopsy, KOH mounts, and fungal
      culture results. We administered topical heat therapy followed by treatment with
      CO2 laser to eradicate the unresponsive remnants of the lesion. The operative
      site re-epithelized within 10 weeks, and 1 year after the treatment there was no
      evidence of recurrence. For a recalcitrant case of chromomycosis, as in this
      case, the use of CO2 laser combined with topical heat therapy may be a new
      therapeutic modality.

PMID- 12195572
TI  - Fatal scleroderma renal crisis caused by gastrointestinal bleeding in a patient
      with scleroderma, Sjogren's syndrome and primary biliary cirrhosis overlap.
AB  - A 57-year-old female patient presented with a long history of overlapping
      autoimmune disease, including limited cutaneous systemic sclerosis, Sjogren's
      syndrome and primary biliary cirrhosis. Another unusual finding was that the mild
      skin involvement (limited cutaneous systemic sclerosis, subcutaneous calcinosis)
      was combined with serious internal organ involvement, including honeycombing and
      finally scleroderma renal crisis. The most important finding was, that two
      decades later she developed severe telangiectasia of the gastrointestinal and
      urinary tract. Furthermore, a specific type of vascular malformation, i.e.
      gastric watermelon stomach was also found. The chronic gastrointestinal bleeding
      primarily derived from a watermelon stomach caused protein overload, which
      provoked the onset of the scleroderma renal crisis that finally led to the
      patient's death.

PMID- 12195574
TI  - Widespread and unusual presentations of cutaneous larva migrans acquired in
      tropical sandy beach resorts.

PMID- 12195573
TI  - A case of loiasis in Rome.
AB  - BACKGROUND: Owing to the increase of an immigrant population and of Italian
      citizens travelling for tourism or on business, it is nowadays possible to
      observe clinical pictures characteristic of tropical regions, often with
      indistinct symptoms. One of these is Loa loa infestation, or loiasis, a form of
      filariasis caused by Loa loa and transmitted by the Chrysops fly. We present the
      case of a male immigrant from Cameroon. Characteristic symptoms were intense
      xerosis, mostly of the third inferior part of the legs, intensely pruritic, with
      numerous lesions from scratching. No benefit was obtained by emollient topics,
      anti-acarus and systemic antihistamines. METHOD: Serum samples and Giemsa,
      haematoxylin, haematoxylin + Giemsa concentration-on-membrane stains, have
      evidenced the presence of Loa loa microfilariae. RESULTS: A diagnosis for L. loa
      (loiasis) infestation was made. CONCLUSIONS: At the beginning of the migration
      phenomenon, particularly from Africa, Italian physicians, especially
      dermatologists, were eagerly looking for 'tropical' diseases; this approach can
      be defined as 'Salgari's syndrome' from the name of the Italian novelist who,
      though never travelling out of Italy, had perfectly described environments and
      habits typical of far away countries. Now, conversely, we have to avoid the
      opposite approach of considering real tropical diseases as related to social or
      psychological difficult conditions.

PMID- 12195575
TI  - Interferon-alpha 2b induced facial erythema in a woman with chronic hepatitis C
      infection.

PMID- 12195576
TI  - A life-threatening exacerbation of lipoid proteinosis.

PMID- 12195577
TI  - Multiple eccrine hidrocystomas.

PMID- 12195578
TI  - Cockayne syndrome with generalized discoid lupus erythematosus-like lesions.

PMID- 12195579
TI  - Topical photodynamic therapy for intraepidermal epithelioma.

PMID- 12195580
TI  - Mycetoma involving the anterior mediastinum and chest wall.

PMID- 12195581
TI  - alpha 1-antitrypsin deficiency in a female with discoid lupus erythematosus.

PMID- 12195582
TI  - Moustache twirler's trichorrhexis nodosa.

PMID- 12195583
TI  - Isolated inguinal tuberculous lymphadenitis.

PMID- 12195584
TI  - Nodular vasculitis associated with chronic hepatitis C.

PMID- 12195585
TI  - Oral terbinafine in the treatment of onychomycosis: a comparison of continuous
      and extended-pause regimens.

PMID- 12195586
TI  - Erythromycin-resistant group A streptococci.

PMID- 12195587
TI  - Transplantation of the right hepatic lobe.

PMID- 12195588
TI  - Transplantation of the right hepatic lobe.

PMID- 12195589
TI  - Transplantation of the right hepatic lobe.

PMID- 12195590
TI  - Transplantation of the right hepatic lobe.

PMID- 12195591
TI  - Transplantation of the right hepatic lobe.

PMID- 12195592
TI  - Luxury primary care.

PMID- 12195593
TI  - Luxury primary care.

PMID- 12195594
TI  - Luxury primary care.

PMID- 12195595
TI  - Luxury primary care.

PMID- 12195596
TI  - Luxury primary care.

PMID- 12195597
TI  - Luxury primary care.

PMID- 12195598
TI  - The impact of premature birth on fear of personal death and attachment of styles
      in adolescence.
AB  - The differences between adolescents born pre-term (n = 50) and a matched sample
      of adolescents born full-term were examined in relation to fear of personal
      death, attachment styles, and the relation between the two variables. Findings
      revealed that adolescents born pre-term showed a higher level of fear of personal
      death and a lower frequency of secure attachment style than adolescents born full
      term. In addition, secure full-term born adolescents exhibited a lower level of
      fear of personal death compared with insecure adolescents; whereas among those
      born pre-term, attachment styles did not affect the level of fear of personal
      death. Results are discussed in terms of the long-term impact of premature birth
      on affect regulation in adolescence.

PMID- 12195599
TI  - Mourning parents: considering safeguards and their relation to health.
AB  - This study investigated the emotional consequences for parents following the
      death of their child. Bereaved parents and age and gender-matched peers completed
      measures of physical health, depression, post-traumatic stress, and personal
      coping resources. To investigate the regulation of emotional reactions, the
      authors used a new instrument consisting of 4 scales: adaptive emotion
      regulation, confiding in others as a means to feeling better, avoiding and hiding
      emotions, and controlling the emotional impact by distorting awareness and
      communication. The bereaved parents were severely affected by the loss; they
      reported high distress levels. However, parents both in the bereavement group as
      well as in a comparison group who had experienced human loss showed better
      ability to control emotions adaptively compared with those who did not report
      such losses. The result is discussed in terms of lifespan development and
      personal growth.

PMID- 12195600
TI  - Family beliefs about end-of-life decisions: an interpersonal perspective.
AB  - Elderly Israelis and their family members (n = 41) from 13 nuclear families were
      interviewed individually and conjointly concerning their beliefs about end-of
      life decisions that would involve prolonging life or hastening death. The
      transcribed interviews were analyzed using the hermeneutic phenomenology approach
      since the purpose of the study was to reveal and interpret beliefs that were not
      easily visible to participants. The premise of the study was that it would be
      possible to identify family beliefs that had been unintentionally, but
      collectively constructed by family members. The results presented 6 belief themes
      and 3 communication strategies that supported our premise. These family beliefs
      and communication patterns have practical implications for professionals working
      with families that are making end-of-life decisions

PMID- 12195601
TI  - Teaching a college course on children and death for 22 years: a supplemental
      report.
AB  - This article supplements an earlier account of experiences involved in teaching
      what is believed to be the first full-term, credit-bearing, college-level course
      on Children and Death (C. A. Corr, 1992). C. A. Corr's article covered a period
      of some 13 years and reported on three phases in the development and early
      history of the course. The present article describes a fourth phase during which
      the Children and Death course was offered in a format of 6 all-day Saturday
      sessions. A plan for the course as it was offered in this last format is
      presented, outlining session titles, goals, topics, methods, and sample resources
      from relevant literature. In addition, this article suggests some lessons
      concerning administration, structure, and content that have emerged from this
      educational experience. Comments from two other faculty members who have taught a
      Children and Death course help to point out why this course is of interest and
      value to instructors and other participants alike.

PMID- 12195602
TI  - Does skin cholesterol testing provide benefit?
AB  - Cholesterol 1,2,3 9 (TM) is being promoted as a non-invasive way to measure
      cholesterol that has accumulated in a person's skin. The test received a medical
      device licence from Health Canada in January 2001. It was approved by the U.S.
      Food and Drug Administration (FDA) in June 2002. This test is not intended to be
      used as a screening tool for coronary artery disease in the general population.
      Evidence from non-randomized, non-blinded clinical trials suggests a correlation
      between higher skin cholesterol levels and the presence of severe coronary
      arterial lesions. At this point, technical improvements and more robust evidence
      are required to determine the significance of this technology in clinical
      practice.

PMID- 12195603
TI  - Tiotropium: a potential replacement for ipratropium in patients with COPD.
AB  - Inhaled tiotropium provides a sustained bronchodilator effect over a 24-hour
      period in patients with chronic obstructive pulmonary disease (COPD). There is
      some evidence that tiotropium 18 micro g once daily is more efficacious than
      ipratropium bromide 40 micro g four times daily, for patients with COPD, as
      measured by improvements in lung function, dyspnea disease-specific quality of
      life and reductions in hospitalization due to COPD. Dry mouth is a more frequent
      problem with tiotropium than with ipratropium bromide.

PMID- 12195604
TI  - Uterine artery embolization for the treatment of fibroids.
AB  - Uterine artery embolization (UAE), or uterine fibroid embolization, is a non
      surgical treatment for uterine fibroids that preserves the uterus and offers
      women an alternative to surgical procedures such as hysterectomy and myomectomy.
      Evidence from controlled trials comparing fibroid treatments is not yet
      available. Case series reports indicate that UAE is a relatively safe and
      effective treatment for symptomatic fibroids. The effect of UAE on fertility and
      pregnancy is not known, though pregnancies following UAE have been reported. UAE
      may reduce health care costs associated with treating fibroids through shorter
      hospital stays and faster recoveries.

PMID- 12195605
TI  - Fondaparinux for post-operative venous thrombosis prophylaxis.
AB  - Fondaparinux (Arixtra TM ) belongs to a new class of synthetic antithrombotic
      agents called pentasaccharides. It was recently approved in Canada for the
      prevention of venous thromboembolic events (VTE) in patients undergoing
      orthopedic surgeries of the lower limbs such as hip fracture, knee surgery and
      hip replacement surgery. Fondaparinux was more efficacious in three of four phase
      III trials comparing fondaparinux and enoxaparin for the prevention of deep vein
      thrombosis (DVT) and/or pulmonary embolism (PE) in patients undergoing major
      orthopedic surgery. However, there was no difference in the incidence of
      pulmonary embolism (PE) between the two treatment groups in any of the four
      trials. The overall major bleeding rate associated with fondaparinux was higher
      than the rate associated with enoxaparin, although the statistical significance
      of this difference is inconsistent.

PMID- 12195606
TI  - Reach-through claims in the age of biotechnology.

PMID- 12195607
TI  - "Stiff in the closet"--who provides care for Parkinsonian patients?

PMID- 12195608
TI  - Canadian EEG standards: a quality issue.

PMID- 12195609
TI  - Progress in clinical neurosciences: Status epilepticus: a critical review of
      management options.
AB  - Although generalized tonic-clonic status epilepticus (SE) is frequently seen, an
      evidence-based approach to management is limited by a lack of randomized clinical
      studies. Clinical practice, therefore, relies on a combination of expert
      recommendations, local hospital guidelines and dogma based on individual
      preference and past successes. This review explores selected and controversial
      aspects of SE in adults and provides a critical appraisal of currently
      recommended management strategies.

PMID- 12195610
TI  - Parkinsonism in Ontario: physician utilization.
AB  - BACKGROUND: Patients with Parkinsonism have a progressive disorder requiring
      substantial expertise to manage effectively. METHODS: Over a six-year period we
      evaluated physician utilization and related costs for a large, unselected cohort
      of 15,304 Parkinsonian patients from the general population, comparing them to
      30,608 age- and sex-matched controls within a universal health care system in
      Ontario, Canada. RESULTS: On average, 45% of Parkinsonian patients saw
      neurologists annually. The cumulative rate of at least one neurological
      consultation was only 59.5% over the six years. Patients aged < 65 had a much
      greater likelihood of consulting a neurologist (73.3%) compared to those > or =
      65 (37.2%). Most Parkinsonian patients (97.2%), regardless of age, saw family
      physicians/general practitioners each year; 50.4% saw internal medicine
      consultants. CONCLUSIONS: Parkinsonian patients had increased likelihood of
      utilizing neurologists, primary care physicians and internists compared to
      controls; related costs of physicians' services were higher. Further research is
      necessary to evaluate differences in outcomes and costs between neurologists and
      other physician service providers.

PMID- 12195611
TI  - High-dose methylprednisolone for acute closed spinal cord injury--only a
      treatment option.
AB  - BACKGROUND: A systematic review of the evidence pertaining to methylprednisolone
      infusion following acute spinal cord injury was conducted in order to address the
      persistent confusion about the utility of this treatment. METHODS: A committee of
      neurosurgical and orthopedic spine specialists, emergency physicians and
      physiatrists engaged in active clinical practice conducted an electronic database
      search for articles about acute spinal cord injuries and steroids, from January
      1, 1966 to April 2001, that was supplemented by a manual search of reference
      lists, requests for unpublished additional information, translations of foreign
      language references and study protocols from the author of a Cochrane systematic
      review and Pharmacia Inc. The evidence was graded and recommendations were
      developed by consensus. RESULTS: One hundred and fifty-seven citations that
      specifically addressed spinal cord injuries and methylprednisolone were retrieved
      and 64 reviewed. Recommendations were based on one Cochrane systematic review,
      six Level I clinical studies and seven Level II clinical studies that addressed
      changes in neurological function and complications following methylprednisolone
      therapy. CONCLUSIONS: There is insufficient evidence to support the use of high
      dose methylprednisolone within eight hours following an acute closed spinal cord
      injury as a treatment standard or as a guideline for treatment.
      Methylprednisolone, prescribed as a bolus intravenous infusion of 30 mg per
      kilogram of body weight over fifteen minutes within eight hours of closed spinal
      cord injury, followed 45 minutes later by an infusion of 5.4 mg per kilogram of
      body weight per hour for 23 hours, is only a treatment option for which there is
      weak clinical evidence (Level I- to II-1). There is insufficient evidence to
      support extending methylprednisolone infusion beyond 23 hours if chosen as a
      treatment option.

PMID- 12195612
TI  - Why do you prescribe methylprednisolone for acute spinal cord injury? A Canadian
      perspective and a position statement.
AB  - OBJECTIVE: To determine the practice patterns for methylprednisolone
      administration for patients with acute spinal cord injury (SCI) within the spinal
      surgery community across Canada, and the reasons behind these patterns. METHODS:
      Canadian neurological and orthopedic spine surgeons were surveyed at their
      respective annual meetings with a questionnaire asking seven questions with
      respect to their practice standards. RESULTS: Sixty surgeons completed the survey
      representing approximately two-thirds of surgeons treating acute SCI within
      Canada. The NASCIS III dosing regimen is the most commonly prescribed steroid
      protocol. However, one-quarter of surgeons do not administer steroids at all. Of
      those who administer methylprednisolone, most do so because of peer pressure or
      out of fear of litigation. CONCLUSIONS: The vast majority of spine surgeons in
      Canada either do not prescribe methylprednisolone for acute SCI, or do so for
      what might be considered the wrong reasons. These results demonstrate the need
      for an evidence-based practice guideline. The Canadian Spine Society and the
      Canadian Neurosurgical Society fully endorse the recommendations of the steroid
      task force (see preceding paper).

PMID- 12195613
TI  - Single dose versus fractionated stereotactic radiotherapy for meningiomas.
AB  - OBJECTIVE: To evaluate the safety and efficacy of stereotactic radiosurgery (SRS)
      compared to fractionated stereotactic radiation therapy (FSRT) for meningiomas
      treated over a seven year period. METHODS AND MATERIALS: Of the 53 patients (15
      male and 38 female) with 63 meningiomas, 35 were treated with SRS and the 18
      patients with tumors adjacent to critical structures or with large tumors were
      treated with FSRT. The median doses for the SRS and the FSRT groups were 1400 cGy
      (500-4500 cGy) and 5400 cGy (4000-6000 cGy) respectively. Median target volumes
      for SRS and FSRT were 6.8 ml and 8.8 ml respectively. The median follow-up for
      the SRS and FSRT groups were 38 months (4.1-97 months) and 30.5 months (6.0-63
      months) respectively. RESULTS: The five-year tumor control probability (TC) for
      benign versus atypical meningiomas were 92.7% vs. 31% (P = .006). The three-year
      TC were 92.7% vs. 93.3% for SRS vs. FSRT groups respectively (P = .62). For
      benign meningiomas, the three-year TC were 92.9% vs. 92.3% for the SRS group (29
      patients) vs. FSRT group (14 patients) respectively (P = .77). Two patients in
      the SRS group and one in the FSRT group developed late complications. CONCLUSION:
      Preliminary data suggest that SRS is a safe and effective treatment for patients
      with benign meningiomas. Fractionated stereotactic radiation therapy with
      conventional fractionation appeared to be an effective and safe treatment
      alternative for patients not appropriate for SRS. A longer follow-up is required
      to determine the long-term efficacy and the toxicity of these treatment
      modalities.

PMID- 12195614
TI  - Outpatient lumbar microdiscectomy: a prospective study in 122 patients.
AB  - BACKGROUND: Outpatient surgery saves the risk of nosocomial complications and
      health care dollars. Patients undergoing lumbar microsurgical discectomy are
      excellent candidates for outpatient surgery. The object of this study was to
      examine the feasibility of performing lumbar microdiscectomy on an outpatient
      protocol and to examine the potential savings associated with such a protocol.
      METHODS: From February 1997 to September, 2001, 122 consecutive patients of the
      senior author were entered into a protocol of outpatient lumbar microdiscectomy.
      Only elective cases were considered for this study. Patients were excluded if
      they had significant co-morbidities, lived a significant distance out of town, or
      if their surgery was scheduled too late in the day. Success was defined as
      discharge home from the day-surgery unit approximately four hours after surgery.
      RESULTS: During the study period, 150 elective lumbar microdiscectomies were
      performed. Twenty-four patients were excluded based on the above criteria and
      four patients requested not to participate in the study. Of the remaining 122,
      116 successfully completed the protocol (95.1%). Six patients were admitted from
      the day surgery unit; two patients with dural tears and four patients with
      anaesthetic side-effects. No patient was readmitted to hospital after discharge
      and no complications of early discharge were observed. There was a total
      reduction in hospitalization of 1.2 nights per elective procedure considering the
      150 patients, when compared with the hospitalization times prior to outpatient
      lumbar microdiscectomy. CONCLUSIONS: Lumbar microdiscectomy can be performed
      safely as an outpatient procedure, resulting in a substantial reduction in
      hospitalization times.

PMID- 12195615
TI  - Spontaneous intracranial hypotension in the absence of magnetic resonance imaging
      abnormalities.
AB  - BACKGROUND: Spontaneous intracranial hypotension (SIH) is a neurologic syndrome
      of unknown etiology, characterized by features of low cerebral spinal fluid (CSF)
      pressure, postural headache and magnetic resonance imaging (MRI) abnormalities.
      METHODS: Four symptomatic cases of SIH presented to our institution over a six
      month period. Magnetic resonance imaging studies were performed in all four
      cases. Diagnostic lumbar puncture was done in all except one case. RESULTS: All
      of the patients on whom lumbar punctures were performed demonstrated low CSF
      pressure and CSF protein elevation with negative cultures and cytology. Three out
      of the four patients exhibited MRI findings of diffuse spinal and intracranial
      pachymeningeal gadolinium enhancement and extradural or subdural fluid
      collections. One patient had no MRI abnormalities despite prominent postural
      headache and reduced CSF pressure at lumbar puncture. All patients recovered with
      intravenous fluids and conservative treatment. CONCLUSIONS: Magnetic resonance
      imaging abnormalities are found in most, but not all patients, with SIH. Cerebral
      spinal fluid abnormalities can be detected even in patients with normal MRI
      studies. It is important to recognize the variability of imaging results in this
      usually benign disorder.

PMID- 12195616
TI  - Electronic case-report forms of symptoms and impairments of peripheral
      neuropathy.
AB  - BACKGROUND AND OBJECTIVE: For the conduct of controlled clinical trials,
      epidemiologic surveys or even of medical practice of varieties of peripheral
      neuropathy, the usefulness, error rate and cost-effectiveness of scannable case
      report forms has not been studied. MATERIALS AND METHODS: The overall
      performance, the frequency of the problems identified and corrected, and the time
      saved from use of a standard paper case report form was evaluated in multicenter
      treatment trials, single center epidemiologic surveys and in our neurologic
      practice. The paper case report form (Clinical Neuropathy Assessment [CNA]) for
      pen entry at study medical centers for patient, disease and demographic
      information (Lower Limb Function [LLF] and Neuropathy Impairment Score [NIS]) can
      be faxed to a core Reading and Quality Assurance Center where the form and data
      is electronically and interactively evaluated and corrected, if needed, by
      participating medical centers before electronic entry into database. OBSERVATIONS
      AND CONCLUSIONS: 1) The approach provides a standard, scannable paper case report
      form for pen entry of neuropathy symptoms, impairments and disability at the
      bedside or in the office which is retained as a source document at the
      participating medical center but a facsimile can be transferred instantaneously,
      its data can be programmed, interactively evaluated, modified and stored while
      maintaining an audit trail; 2) it allowed efficient and accurate reading,
      transfer, analysis, and storage of data of more than 15,000 forms used in
      multicenter trials; 3) in 500 consecutive CNA evaluations, software programs
      identified and facilitated interactive corrections of omissions, discrepancies,
      and disease and study inconsistencies, introducing only a few readily identified
      and corrected entry errors; and 4) use of programmed, as compared to non
      programmed assessment, was more accurate than double keyboard entry of data and
      was approximately five times faster.

PMID- 12195618
TI  - Accidental hydrogen peroxide ingestion.

PMID- 12195617
TI  - Human autologous in vitro models of glioma immunogene therapy using B7-2, GM-CSF,
      and IL12.
AB  - BACKGROUND: Cancer immunogene therapy is based on vaccination with radiated,
      autologous tumor cells transduced with immunostimulatory genes. To help determine
      an optimal glioma immunogene therapy strategy, we stimulated lymphocytes with
      autologous human glioma cells transduced with B7-2 (CD86), granulocyte-macrophage
      colony-stimulating factor (GM-CSF), and/or interleukin-12 (IL12). METHODS: A
      human glioma-derived cell culture (Ed147.BT) was transduced with B7-2, GM-CSF,
      and/or IL12 using retroviral vectors. Autologous peripheral blood mononuclear
      cells (PBMC) were co-cultured with irradiated gene-transduced tumor alone or a
      combination of radiated wild type and gene-transduced cells. Peripheral blood
      mononuclear cells proliferation was determined by serial cell counts. Peripheral
      blood mononuclear cells phenotype was assessed by flow cytometry for CD4, CD8,
      and CD16. Anti-tumor cytotoxicity was determined by chromium-51 (51Cr) release
      assay. RESULTS: Peripheral blood mononuclear cells cell numbers all decreased
      during primary stimulation but tumor cells expressing B7-2 or GM-CSF consistently
      caused secondary proliferation. Tumors expressing B7-2 and GM-CSF or B7-2, GM
      CSF, and IL12 consistently increased PBMC CD8+ (cytotoxic T) and CD16+ (natural
      killer) percentages. Interestingly, anti-tumor cytotoxicity only exceeded that of
      PBMC stimulated with wild type tumor alone when peripheral blood mononuclear
      cells were stimulated with both wild type tumor and B7-2/GM-CSF- (but not IL12)
      transduced cells. CONCLUSIONS: PBMC proliferation and phenotype is altered as
      expected by exposure to immunostimulatory gene-transduced tumor. However,
      transduced tumor cells alone do not stimulate greater anti-tumor cytotoxicity
      than wild type tumor. Only B7-2/GM-CSF-transduced cells combined with wild type
      produced increased cytotoxicity. This may reflect selection of tumor subclones
      with limited antigenic spectra during retrovirus-mediated gene transfer.

PMID- 12195619
TI  - Pneumocephalus as a cause for headache.
AB  - BACKGROUND: Pneumocephalus can be a cause of headache, but is easily overlooked
      in some clinical circumstances. CASE STUDY: A 35-year-old woman developed severe
      headache of abrupt onset during an epidural blood patch procedure done for a post
      lumbar puncture headache. A brain CT scan showed subarachnoid air even though
      there was no evidence of a dural puncture having occurred during the procedure.
      RESULTS: The experience of our patient, and a review of the literature suggests
      that air injected into the epidural space during use of the "loss of resistance"
      technique can enter the subarachnoid space if a dural puncture site from a
      previous lumbar puncture is present. CONCLUSIONS: Pneumocephalus should be
      considered as a potential cause for a severe headache occurring in association
      with epidural procedures, and also in a number of other clinical settings. Use of
      a high inspired air oxygen concentration can hasten absorption of an intracranial
      air collection.

PMID- 12195620
TI  - Jules Bernard Luys: a singular figure of 19th century neurology.
AB  - Jules Bernard Luys was a highly industrious and dedicated French investigator who
      made important contributions to the fields of neuroanatomy and neuropsychiatry in
      the second half of the 19th century. His name is still eponymically attached to
      the subthalamic nucleus and the centre median nucleus, two structures that are at
      the center of our current thinking about the functional organization of the basal
      ganglia and the pathophysiology of Parkinson's disease. While developing a highly
      original view of the anatomical and functional organization of the human brain,
      Luys contributed significantly to our knowledge of the neuropathological and
      clinical aspects of mental illnesses. Luys devoted the last part of his career to
      hysteria and hypnosis, engaging himself in experiments as extravagant as the
      action of medication at distance. In doing so, he became perhaps the most highly
      caricatured example of the fascination that hysteria exerted upon various
      renowned neurologists at the end of the 19th century. This paper briefly
      summarizes the contribution of this remarkable figure of the history of
      neurology.

PMID- 12195622
TI  - Information Services Building, University of Otago. Dunedin, New Zealand.

PMID- 12195621
TI  - Head injuries in skiers and snowboarders.

PMID- 12195623
TI  - Donald Danforth Plant Science Center. Creve Coeur, Missouri.

PMID- 12195624
TI  - Genetic epidemiology of juvenile idiopathic arthritis.
AB  - Juvenile idiopathic arthritis (JIA) is a heterogeneous group of disorders.
      Although the pathogenesis is not completely understood, many studies point to a
      genetic component in the susceptibility for this disease with environmental
      factors also contributing to the pathogenesis. The genetic component of JIA is
      complex, involving the effects of multiple genes at various points in the disease
      pathology. The best documented association is with the genes within the Human
      Leukocyte Antigen (HLA) complex, encoding the classical peptide-presenting
      molecules. JIA is associated with particular alleles at, at least, three
      different HLA loci: HLA-A (HLA-A*0201), -DR/DQ (DRB1*08, DRB1*11, DRB1*13) and 
      DP (DPB1*0201, DPB1*0301), with marked differences between the disease subtypes.
      Non-HLA genes may also contribute to the disease. Many of these genes encode
      cytokines and probably regulate their production. Examples of such cytokines
      involved in JIA are interleukin-1 alpha (IL-1 alpha), interleukin-1 receptor
      antagonist (IL-1Ra), interleukin-6 (IL-6), interleukin-10 (IL-10), macrophage
      inhibitory factor (MIF), interferon regulatory transcription factor (IFN1).
      Accumulated data suggest that interactions between the genes are necessary for
      the development of the disease. Knowledge of the genes involved would help to
      understand the molecular mechanisms involved in the pathogenesis of JIA and may
      have implications for prognosis and therapy.

PMID- 12195625
TI  - The complement system in systemic lupus erythematosus.
AB  - The etiology of SLE is multifactorial with an important genetic impact. Several
      genes involved in control of autoimmunity and inflammation appear to be
      important. Hereditary complement deficiency states are associated with increased
      risk of SLE, but contribute only marginally to the incidence of SLE in the
      population. However, these conditions have contributed considerably to the
      knowledge of pathogenetic mechanisms in this disease. Furthermore, acquired
      complement deficiency is a common finding in SLE. Complement has important
      protective functions but also contributes to tissue damage. Measurement of
      classical pathway complement components is important in the diagnosis of SLE and
      for monitoring of immune complex mediated manifestations, especially
      proliferative glomerulonephritis. New complement activation tests, although
      promising in studies of selected patient groups, have not yet been proven to be
      of clinical value.

PMID- 12195627
TI  - Estimation of Sjogren's syndrome among IBD patients. A six year post-diagnostic
      prevalence study.
AB  - OBJECTIVE: To study the prevalence of Sjogren's syndrome (SS), tear and saliva
      production and sicca symptoms in patients with inflammatory bowel disease (IBD)
      seen six years after IBD diagnosis. METHODS: In a population based cohort of 654
      patients with IBD, 521 patients (80%) and a control group consisting of 68
      healthy subjects were investigated. SS was diagnosed according to the European
      Criteria proposed by the American-European Consensus Group (US-EU criteria) and
      the European criteria. Maximum (supposing positive biopsies) and minimum
      prevalences (supposing negative biopsies) were estimated. RESULTS: Dryness of
      eyes and mouth were similarly distributed between patients with ulcerative
      colitis (UC) and Crohn's disease (CD) and between patients and controls. The
      prevalence of SS was 0-4.2% and 0-5.7% (minimum-maximum) according to the US-EU
      criteria and the European criteria, respectively. The controls fulfilled neither
      of the criteria. CONCLUSION: Sjogren's syndrome, sicca symptoms, tear and saliva
      production were not increased in patients with IBD compared to controls,
      indicating a lack of association between SS and IBD.

PMID- 12195626
TI  - Serial analysis of Ro/SSA and La/SSB antibody levels and correlation with
      clinical disease activity in patients with systemic lupus erythematosus.
AB  - OBJECTIVE: To investigate the temporal correlation between anti-Ro/SSA and anti
      La/SSB antibody levels and compare them with variation in clinical disease
      activity in patients with systemic lupus erythematosus (SLE). METHODS: Sequential
      serum samples collected over 18-44 months from 18 anti-Ro/SSA positive patients
      with systemic lupus erythematosus were analysed by ELISA with recombinant Ro60,
      Ro52 and La antigens. Disease activity was assessed by the BILAG index. RESULTS:
      Limited antibody level variation over time was found in most patients, but a
      subset displayed more changes and a co-variation between the levels of separate
      specificities was found in 40% of patients. In two patients antibody levels
      fluctuated with the global score. Antibodies also correlated with separate
      organ/systems involvement in individual patients. CONCLUSION: The Ro60, Ro52 and
      La antibody profile is fixed at an early stage of disease and in most patients
      hardly changes. Patients with fluctuating levels tend to have a co-ordinated
      expression of these autoantibodies.

PMID- 12195628
TI  - Simple function tests, but not the modified HAQ, correlate with radiological
      joint damage in rheumatoid arthritis.
AB  - OBJECTIVE: To test the validity of the Modified Stanford Health Assessment
      Questionnaire (MHAQ) for assessment of physical disability in rheumatoid
      arthritis (RA). METHODS: Sixty-one RA patients with mean age of 61 years and
      median disease duration of four years were included in this cross sectional
      study. The patients completed the MHAQ. Four simple function tests were performed
      (walk test, chair test, upper extremity mobility test, and grip strength) and a
      modified Larsen score was established. Pain score (VAS) and laboratory variables
      for inflammation were recorded. RESULTS: MHAQ, function tests, pain, and C
      reactive protein (CRP) showed highly significant mutual correlations (p < 0.01).
      However, MHAQ did not correlate with Larsen score (R = 0.06; NS), while most
      function tests did (walk test, R = 0.29; p < 0.05; chair test, R = 0.21; NS;
      mobility test, R = 0.36; p < 0.01 and grip strength, R = -0.35 p < 0.01). The
      superiority of function tests was even more pronounced after four years (walk
      test, R = 0.31; p < 0.05; chair test, R = 0.50; p < 0.01; mobility test, R =
      0.49; p < 0.01; grip strength, R = -0.52; p < 0.01; MHAQ, R = 0.34; NS).
      CONCLUSION: Objective function tests are preferable to MHAQ in the assessment of
      physical disability in RA.

PMID- 12195629
TI  - New potential markers for cartilage degradation of the knee joint.
AB  - OBJECTIVE: To determine the correlation of biochemical markers with the degree of
      cartilage degradation. METHODS: In a cross-sectional study, synovial fluid
      samples were obtained from 65 patients with cartilage lesions of the knee joint.
      The measured biochemical markers included MMP-1, MMP-3, and MMP-13, the tissue
      inhibitor of MMPs (TIMP-1), COMP, YKL-40, and tenascin. The marker levels were
      compared with the Outerbridge and the Noyes classification. RESULTS: For the
      majority of markers, the correlation coefficient was below r = 0.3. The highest
      correlation coefficients were obtained from tenascin (r = 0.66 and 0.67) and MMP
      13 (r = 0.44 and 0.41). CONCLUSION: The overall results indicate that the
      majority of the tested markers is unspecific with regard to the different stages
      of the two classifications. However, tenascin and MMP-13 could be of clinical
      importance to indicate advanced stages. Yet the values of these markers in
      longitudinal studies are not known.

PMID- 12195630
TI  - Enthesitis of proximal insertion of the deltoid in the course of seronegative
      spondyloarthritis. An atypical enthesitis that can mime impingement syndrome.
AB  - OBJECTIVE: To study the frequence of deltoideal proximal insertion enthesitis
      (DPIE) in patients affected with spondyloarthritis (SpA) and to evaluate its
      clinical, sonographic and radiological characteristics. METHODS: A retrospective
      study of clinical, sonographic and radiological examinations of the shoulders of
      100 symptomatic consecutive outpatients with SpA, compared to 4 groups of control
      patients: 100 with Rheumatoid Arthritis, 100 with Osteoarthritis, 100 with
      Painful Shoulder, and 50 with shoulders undamaged by local pathological
      processes. RESULTS: The frequence of DPIE in the course of SpA was 9%. DPIE
      appears most frequently in Psoriatic Arthritis (PsA) (17%, 7/41). DPIE does not
      appear to be related to the sex or the age of the patient. The clinical signs and
      symptoms are similar to those of an impingement syndrome. Sonography reveals
      thickening and hypoechogenicity of the enthesis, associated or not to the
      subchondral osseous rearrangement and enthesophytosis. Radiology only reveals the
      enthesophytosis in the later stages. CONCLUSIONS: DPIE can determine shoulder
      pain in the course of SpA, and in particular in PsA. The clinical manifestations
      of DPIE are very similar to those of an impingement syndrome; sonography can
      differentiate the two conditions.

PMID- 12195631
TI  - Exercise habits among patients with ankylosing spondylitis. A questionnaire based
      survey in the County of Vasterbotten, Sweden.
AB  - OBJECTIVE: This study aimed at evaluating exercise habits among patients with
      ankylosing spondylitis, their clinical status and what mainly restrains these
      patients from exercising. METHODS: In a cross-sectional design study 189 patients
      completed a self-administrated questionnaire regarding their exercise habits and
      their clinical status. RESULTS: A majority of the patients reported that they
      performed exercises. The most popular form of exercise was walking. Pool exercise
      was perceived to relieve the symptoms more than any other exercise and was also
      rated as the most enjoyable form of exercise. The main obstacle to exercise was
      lack of time, followed by fatigue. A small number of patients experienced
      aggravation of symptoms with exercise. CONCLUSION: A majority of AS patients
      exercise, although the frequency of the exercise was low for many patients. The
      main obstacle to exercise was lack of time and fatigue.

PMID- 12195632
TI  - Does a regular exercise program for ankylosing spondylitis influence body image?
AB  - OBJECTIVE: To investigate whether participation in a regular exercise programme
      by patients with ankylosing spondylitis (AS) had a positive impact on their body
      image. METHODS: Semi-structured interview and several questionnaired assessed
      exercise compliance, mood and other facets of disease impact. Body image was
      assessed using the Arthritis Body Experience Scale, which measured the concepts
      of body totality and body self-consciousness. RESULTS: No correlation was found
      between exercise for AS and body image. However, body totality correlated with
      acceptance of illness (p = 0.37, p < 0.05) and both measures of body image
      inversely correlated with depression (p < 0.05). CONCLUSION: Normally, regular
      exercise has a positive effect on body image, but in AS, from this small study it
      seems that the recommended exercise program does not influence body image, which
      in these patients seems more closely related to mood. This warrants further
      evaluation, as a better understanding of influences on body image might improve
      compliance with therapeutic regimens.

PMID- 12195633
TI  - Beneficial effect of climatic therapy on inflammatory arthritis at Tiberias Hot
      Springs.
AB  - OBJECTIVE: To examine the beneficial effect of climatic therapy at the Tiberias
      Hot Springs on patients with inflammatory arthritis. METHODS: Patients from
      Sweden with inflammatory arthritis underwent climatic therapy for 4 weeks at the
      Tiberias Hot Springs in Israel. Patients were examined at the beginning and end
      of the therapy and were evaluated as responders according to internationally
      validated criteria. RESULTS: One hundred-thirty-six patients were evaluated, 83
      with a clinical course of rheumatoid arthritis (RA) and 53 with ankylosing
      spondylitis (AS). Forty-seven (57%) of the RA patients and 32 (60%) of the AS
      patients were considered responders. Shorter disease duration and more active
      disease were associated with a greater response in RA, while in AS males
      responded more often than females. CONCLUSION: Most patients benefited
      significantly from climatic therapy. Long-term follow-up is necessary to see
      whether improvement is sustained and if work ability and hospitalizations are
      also improved.

PMID- 12195634
TI  - Angioedema and systemic sclerosis. A review of the literature.
AB  - We report a case of chronic idiopathic recurrent urticaria-angioedema and
      gastroesophageal reflux disease in a 35-years-old man, followed after 2 years by
      Raynaud's phenomenon and esophageal dysphagia, recurrent cough and dyspnoea, and
      after 4 years by systemic sclerosis. A review of the literature and possible
      correlated pathogenetic mechanisms are presented.

PMID- 12195635
TI  - Adult onset Still's disease as a cause of ARDS and acute respiratory failure.
AB  - We report a case of a young woman with pyrexia and progressive lung disease who
      developed acute respiratory distress syndrome (ARDS) and required prolonged
      mechanical ventilator support. The patient had a markedly elevated serum ferritin
      concentration of 7880 micrograms/L, a specific finding for the adult onset
      Still's disease (AOSD). Treatment of the patient with supportive and
      immunosuppressive therapy, resulted in patient survival and cure. The early
      consideration of the diagnosis of AOSD in patients with fever of unknown origin
      and a compatible clinical course may modify its severe complications.

PMID- 12195636
TI  - Nodular fasciitis, erythema migrans, and oligoarthritis: manifestations of Lyme
      borreliosis caused by Borrelia afzelii.
AB  - We describe a 35-year old patient with nodular fasciitis, erythema migrans, and
      gonarthritis four months after a bite of a Borrelia afzelii infected tick. The
      Borrelia afzelii infection was identified by a polymerase chain reaction and
      direct sequencing of the amplification product. Borrelia-specific DNA was also
      detectable in nodular fasciitis tissue. We therefore conclude that Borrelia
      afzelii can be a causative agent of nodular fasciitis and Lyme arthritis in a
      highly endemic region of Northern Germany.

PMID- 12195637
TI  - A comprehensive worksite cancer prevention intervention: behavior change results
      from a randomized controlled trial (United States).
AB  - OBJECTIVE: Workplace cancer prevention initiatives have been least successful
      with blue-collar workers. This study assess whether an intervention integrating
      health promotion with occupational health and safety results in significant and
      meaningful increases in smoking cessation and consumption of fruits and
      vegetables, compared to a standard health promotion intervention, for workers
      overall and for blue-collar workers in particular. METHODS: A randomized
      controlled design was used, with 15 manufacturing worksites assigned to a health
      promotion (HP) or a health promotion plus occupational health and safety
      intervention (HP/OHS), and compared from baseline (1997) to final (1999). The
      response rates to the survey were 80% at baseline (n = 9019) and 65% at final (n
      = 7327). Both groups targeted smoking and diet; the HP/OHS condition additionally
      incorporated reduction of occupational exposures. RESULTS: Smoking quit rates
      among blue-collar workers in the HP/OHS condition more than doubled relative to
      those in the HP condition (OR = 2.13, p = 0.04), and were comparable to quit
      rates of white-collar workers. No statistically significant differences between
      groups were found for mean changes in fruits and vegetables. CONCLUSIONS:
      Integration of occupational health and safety and health promotion may be an
      essential means of enhancing the effectiveness of worksite tobacco control
      initiatives with blue-collar workers.

PMID- 12195638
TI  - Disseminating research findings into public health practice.

PMID- 12195639
TI  - In-utero exposures and breast cancer risk: joint effect of estrogens and insulin
      like growth factor?
AB  - Initial evidence from observational studies led to the suggestion that high
      maternal estrogens in-utero are central factors in the development of adult
      breast cancer. Subsequently, several studies attempted to illuminate this
      hypothesis, but few of the more detailed observational studies show a clear and
      strong association between prenatal estrogen exposure and breast cancer risk in
      adulthood. To date, the potential underlying biological mechanisms remain unclear
      and controversial. However, recent observations of a relation between insulin
      like growth factor-1 (IGF-1) and breast cancer risk may shed new light on the
      role of in-utero exposure, early growth, and risk of breast cancer. More research
      is needed to elucidate this potential mechanism.

PMID- 12195640
TI  - Nonlinear relationship of insulin-like growth factor (IGF)-I and IGF-I/IGF
      binding protein-3 ratio with indices of adiposity and plasma insulin
      concentrations (Sweden).
AB  - OBJECTIVE: In this study we test the hypothesis of a nonlinear relationship of
      IGF-I with indices of body fat such as body mass index (BMI), insulin, and
      leptin. METHODS: The controls used in three case-control cancer studies nested in
      the Northern Sweden Health and Disease Cohort, were combined for this analysis.
      Measurements of plasma IGF-I, IGFBP-3, insulin, and leptin were available for 445
      men and 391 women. RESULTS: In both men and women we found the highest mean IGF-I
      levels in subjects with BMI between 24 and 26. IGF-I concentrations decreased
      toward BMI < or = 20 and BMI > 30 in men; however, the results for women did not
      reach statistical significance. The molar ratio of IGF-I/IGFBP-3 showed a similar
      profile to that of IGF-I, although much less pronounced. The observed peak mean
      IGF-I levels in the second quintiles of insulin and leptin in men supported these
      findings. No significant variation of mean IGF-I levels across quintiles of
      insulin and leptin were observed in women. CONCLUSIONS: The results of this study
      provide evidence that IGF-I plasma concentrations vary substantially over a wide
      range of body weight and that the relationship is nonlinear.

PMID- 12195641
TI  - Serum selenium and the risk of cervical cancer among women in the United States.
AB  - OBJECTIVE: To explore the relationship between serum selenium and cervical
      cancer. METHODS: We conducted a case-control study of cervical cancer in five
      areas around Birmingham, AL; Chicago, IL; Denver, CO; Miami, FL; and
      Philadelphia, PA. Community controls were selected by random-digit dialing and
      were matched to invasive cervical cancer cases by age, race/ethnicity, and
      telephone exchange. Serum selenium was determined by neutron activation analysis.
      Logistic regression analysis controlling for known risk factors of cervical
      cancer, including human papillomavirus (HPV) type-16 measured serologically, was
      performed on 227 invasive cases, 127 in-situ cases, and 526 controls. RESULTS:
      Values of serum selenium ranged from 67.5 to 185.0 ng/ml. Adjusted odds ratios
      for invasive cervical cancer by quintile were: 1.0 (highest selenium), 1.1, 1.0,
      0.8, and 1.0 (lowest selenium), p for trend = 0.82. Similar patterns were
      observed for Stage I invasive, and Stages II-IV invasive cases, suggesting
      severity of disease did not influence the null results. Although no associations
      were seen among current or never smokers, a protective effect of selenium was
      suggested among former smokers. Effect modification was not evident for other
      variables examined. CONCLUSIONS: This study does not support a relationship
      between serum selenium and invasive cervical cancer at typical serum selenium
      levels in the US.

PMID- 12195642
TI  - GSTM-1 and NAT2 and genetic alterations in colon tumors.
AB  - OBJECTIVE: Phase II metabolizing enzymes such as glutathione S-transferases and N
      acetyltransferase are involved in the detoxification of carcinogens. Genetic
      variants of genes coding for these enzymes have been evaluated as to their
      association with colon cancer, both as independent risk factors and as effect
      modifiers for associations with diet and cigarette smoking. In this study, we
      evaluate associations between the GSTM-1 genotype and the NAT2-imputed phenotype
      and acquired mutations in tumors. METHODS: Data is taken from a set of 1836 cases
      and 1958 controls with colon cancer who were part of a large case-control study
      of colon cancer and whose tumors were previously analyzed for Ki-ras, p53, and
      microsatellite instability (MSI). We also evaluate the modifying effects of these
      genetic variants with diet and cigarette smoking, factors previously identified
      as being associated with specific tumor alterations. RESULTS: Neither GSTM-1 nor
      the NAT2-imputed phenotype was independently associated with Ki-ras, p53, or MSI.
      Cigarette smoking significantly increased the risk of tumors involving the MSI
      pathway. Additionally, cigarette smoking doubled the risk of p53 transversion
      mutations among those who were GSTM-1 present. Cases were slightly more likely to
      have a p53 mutation if they frequently consumed red meat and had the imputed NAT2
      intermediate/rapid phenotype relative to slow phenotype/infrequent consumers of
      red meat (OR 2.0, 95% CI 1.3-3.0 for intermediate/rapid). CONCLUSIONS: These data
      provide support that diet and cigarette smoking may be associated with specific
      disease pathways, although GSTM-1 and NAT2 do not independently appear to alter
      susceptibility to these diet and lifestyle factors.

PMID- 12195643
TI  - Aspirin, other NSAIDs, and ovarian cancer risk (United States).
AB  - OBJECTIVE: We sought to evaluate the association between ovarian cancer risk and
      use of aspirin and nonsteroidal anti-inflammatories. METHODS: We prospectively
      assessed use of aspirin, nonsteroidal anti-inflammatories (NSAIDs), and
      acetaminophen use in relation to ovarian cancer risk among 76,821 participants in
      the Nurses' Health Study who had no history of cancer other than non-melanoma
      skin cancer. Women reported known and suspected ovarian cancer risk factors in
      biennial mailed questionnaires from 1976 to 1996, along with new diagnoses of
      ovarian cancer. Aspirin use was assessed in 1980, 1982, 1984, and 1988-1994. We
      assessed NSAID use in 1980, and both NSAID and acetaminophen use in 1990, 1992,
      and 1994. During 16 years of follow-up and 1,222,412 person-years, 333 cases of
      invasive epithelial ovarian cancer were confirmed. We used pooled logistic
      regression to control for age, body mass index, oral contraceptive use, smoking
      history, parity, postmenopausal hormone use, tubal ligation, and other potential
      ovarian cancer risk factors. RESULTS: Aspirin use was not associated with ovarian
      cancer risk overall (RR for users compared with nonusers, 1.00, 95% confidence
      interval (CI 0.80-1.25). We found no association between aspirin dose (in number
      of weekly tablets) and ovarian cancer risk (RR for those taking 15 or more
      tablets weekly compared with nonusers, 0.98, 95% CI 0.63-1.52). Similarly,
      duration of aspirin use was not associated with risk (RR for aspirin use of 20 or
      more years, 0.99, 95% CI 0.69-1.43). In separate models assessing the relation
      between NSAID use and ovarian cancer risk we found a 40% reduction in risk among
      NSAID users versus nonusers (RR 0.60, 95% CI 0.38-0.95). However, when we
      examined this relationship in terms of days of NSAID use per month, we did not
      observe a dose-response with increasing NSAID use. CONCLUSIONS: We observed no
      association between aspirin use, dose, or duration and epithelial ovarian cancer
      risk. Although we found a modest reduction in risk associated with NSAID use,
      there was no dose-effect.

PMID- 12195644
TI  - Breast cancer survival in African American women: is alcohol consumption a
      prognostic indicator?
AB  - OBJECTIVE: Compromised breast cancer survival in African American women is well
      established. Factors associated with poorer survival in this group are not fully
      elucidated. This analysis examined the influence of alcohol consumption on breast
      cancer survival in African American women accrued to a hospital-based study.
      METHODS: One hundred twenty-five postmenopausal women (mean age = 64.2 +/- 12.2
      years) diagnosed with invasive breast carcinoma between August 1989 and December
      1994, and accrued to a hospital-based study of the disease, were followed for
      survival through December 1998. Cox proportional hazards regression models,
      adjusted for cigarette smoking, summary stage of disease, and treatment explored
      the association between alcohol use and breast cancer survival. RESULTS:
      Premorbid alcohol consumption of at least one drink per week was associated with
      2.7-fold increase in risk of death (95% CI 1.3-5.8). CONCLUSIONS: This study
      suggests compromised breast cancer survival among postmenopausal women who
      reported drinking at least one alcoholic beverage per week, a preliminary finding
      that warrants further investigation.

PMID- 12195645
TI  - Folate, methionine, alcohol, and colorectal cancer in a prospective study of
      women in the United States.
AB  - OBJECTIVE: We investigated the associations of folate, methionine, and alcohol
      intake, as well as combinations of these factors, with risk of colorectal cancer
      (CRC). METHODS: We assessed diet using a 62-item food-frequency questionnaire
      among 45,264 women in the Breast Cancer Detection Demonstration Project (BCDDP)
      Follow-up Study. After an average of 8.5 years of follow-up, 490 cases of CRC
      were identified. RESULTS: Dietary folate showed only a slight inverse association
      with the risk of CRC (RR = 0.86, 95% CI 0.65-1.13 for high vs. low quintile, p
      for trend = 0.14), and the association for total folate was null. Consuming more
      than two servings of alcohol per day was only slightly associated with CRC in
      this cohort (RR = 1.16, 95% CI 0.63-2.14). Combinations of high alcohol and low
      total folate did not result in a higher risk of CRC. There was no association
      between methionine and colorectal cancer. CONCLUSIONS: This study shows limited
      association between alcohol intake and CRC. The non-association of total folate
      and methionine with CRC, and the null results from the combined folate and
      alcohol analyses, suggest that what effect alcohol may have on CRC is unrelated
      to the methyl-group metabolism pathway.

PMID- 12195646
TI  - Animal-related occupations and the risk of leukemia, myeloma, and non-Hodgkin's
      lymphoma in Canada.
AB  - OBJECTIVE: There is some evidence to suggest that workers in animal-related
      occupations are at increased risk of developing lymphohematopoietic cancers. This
      study aimed to examine the risk of leukemia, non-Hodgkin's lymphoma (NHL), and
      multiple myeloma associated with occupational exposure to animals. METHODS: We
      used data from a multi-site, population-based case-control study using mailed
      questionnaires which had taken place in eight of ten Canadian provinces, during
      1994-1998. There were 1023 leukemia cases, 1577 NHL cases, and 324 multiple
      myeloma cases (all histologically confirmed) and 4688 population-based controls.
      Animal-related occupations were identified from a lifetime occupational history.
      Subjects in animal-related jobs were compared with others using logistic
      regression for the risk of leukemia, NHL, and multiple myeloma. RESULTS: Compared
      to subjects without occupational exposure to animals, occupational exposure to
      beef cattle increased the risks of leukemia (odds ratio (OR) 2.0, 95% confidence
      interval (CI) 1.2-3.3) and NHL (OR 1.8, 95% CI 1.1-2.9). No other animal exposure
      was consistently associated with risk of lymphohematopoietic cancer. An
      unexpected protective association was observed between work as a fisherman and
      leukemia (OR 0.4, 95% CI 0.2-0.8) and NHL (OR 0.6, 95% CI 0.4-0.9). CONCLUSIONS:
      This population-based case-control study found that those individuals working in
      occupations associated with beef cattle are at increased risk for developing
      leukemia and lymphoma while those working in occupations requiring the handling
      of fish are at decreased risk of leukemia and lymphoma.

PMID- 12195647
TI  - A prospective cohort study on intake of retinol, vitamins C and E, and
      carotenoids and prostate cancer risk (Netherlands).
AB  - OBJECTIVES: The roles of retinol, vitamins C and E, and carotenoids as risk
      factors for prostate carcinoma are still questionable. We evaluated these in the
      Netherlands Cohort Study. METHODS: The cohort study consisted of 58,279 men ages
      55-69 years at baseline in 1986. After 6.3 years of follow-up, 642 incident
      prostate carcinoma cases were available for analysis. Intakes of retinol,
      vitamins C and E, and several carotenoids were measured by means of a 150-item
      semi-quantitative food-frequency questionnaire. RESULTS: In multivariate analyses
      a positive association with prostate cancer risk was observed for intake of beta
      cryptoxanthin. Rate ratios (RRs) in increasing quintiles were 1.00 (ref), 0.94,
      1.01, 1.16, 1.41; p-trend < 0.01. For intake of retinol, vitamins C and E and
      other carotenoids (alpha-carotene, beta-carotene, lycopene, and
      lutein/zeaxanthin) no effect on overall prostate cancer risk was found. RRs for
      vitamin supplement use were decreased, but not significantly. Among nondrinkers,
      nonsignificant inverse associations were observed for intake of retinol, alpha
      carotene, and beta-carotene (RRs, highest vs lowest quintile, were 0.23, 0.60,
      and 0.76, respectively). Among drinkers, beta-cryptoxanthin was positively
      associated (RR highest vs lowest quintile = 1.40). CONCLUSIONS: These data show a
      positive association between beta-cryptoxanthin and prostate cancer risk. Our
      study also shows inverse associations for retinol, alpha-carotene, and beta
      carotene among nondrinkers; this suggests an interaction between vitamins and
      alcohol consumption, which needs confirmation. Lycopene was not associated with
      prostate cancer.

PMID- 12195648
TI  - Estrogen and estrogen-progestin replacement therapy and risk of postmenopausal
      breast cancer in Canada.
AB  - OBJECTIVE: To examine the association between hormone replacement therapy (HRT)
      use and breast cancer incidence and to determine whether the association differs
      according to type of regimen. METHOD: Data were collected in Ontario from 404
      incident cases and 403 age frequency-matched controls, between 1995 and 1996,
      using a self-administered questionnaire. RESULTS: Multivariate analyses revealed
      an elevated odds ratio among long-term (> or = ten years) HRT users (odds ratio
      (OR) = 1.80, 95% confidence interval (CI) 1.06-3.06). Risk among long-term
      estrogen-progestin users was substantially higher (OR = 3.48, 95% CI 1.00-12.11)
      than risk among long-term users of estrogen alone (OR = 1.74, 95% CI 0.93-3.24).
      Among both estrogen and estrogen-progestin users, positive associations were not
      observed for durations of use less than ten years. CONCLUSION: These data suggest
      that long-term use of HRT increases the risk of breast cancer and that estrogen
      progestin therapy may be more detrimental than estrogen use alone.

PMID- 12195650
TI  - The placebo effect. Congress hopes you won't notice its prescription-drug plans
      are meant to help candidates, not patients.

PMID- 12195649
TI  - Report from a symposium on diet and breast cancer.
AB  - On 21 September 2001 the Harvard Center for Cancer Prevention and the Cancer
      Epidemiology Program of the Dana-Farber/Harvard Cancer Center co-sponsored a
      symposium on diet and breast cancer for members of the Harvard breast cancer
      research community in Boston, MA. The purpose of the symposium was to review past
      findings and recent research developments in diet and breast cancer, and to
      potentially identify new opportunities for study. Presentations addressed
      research on the associations between phytoestrogens, total dietary fat, types of
      fat, olive oil, alcohol, folate/folic acid, and intakes of fruits and vegetables,
      and breast cancer risk. The relations between metabolic factors such as body mass
      index, weight gain, and breast cancer risk were also highlighted.

PMID- 12195651
TI  - Time of their lives--Camp Heartland.

PMID- 12195652
TI  - Death on the sand.

PMID- 12195653
TI  - Deadly feast: can venison kill you?

PMID- 12195654
TI  - West Nile on the move.

PMID- 12195655
TI  - Why didn't I think of this sooner!

PMID- 12195656
TI  - Primary care? Not me.

PMID- 12195657
TI  - The way I see it. We have to stand up for the children.

PMID- 12195658
TI  - Lead patients to your door.

PMID- 12195659
TI  - When it's time to give an employee the boot.

PMID- 12195660
TI  - Workplace chaplains: filling a need traditional EAPs can't meet.
AB  - More organizations are finding secular counseling provided by employee assistance
      programs (EAPs) is inadequate for many employees. As a result, increasing numbers
      of employers are providing services of workplace chaplains. Chaplain services are
      not necessarily part of the recent fad toward "spirituality" in organizations,
      but rather address the needs of an increasingly non-churchgoing culture living in
      a more stressful world.

PMID- 12195661
TI  - Disclosure--estoppel, equitable relief, attorney fees. Bowerman v. Wal-Mart
      Stores, Inc.

PMID- 12195662
TI  - Arbitration clauses--disclosure--remedy. Chappel v. Laboratory Corporation of
      America.

PMID- 12195663
TI  - Sweet deal. Aramark to buy Premier's services unit.

PMID- 12195664
TI  - Yellow light on Wall Street. Neoforma may face restatement of financial results.

PMID- 12195665
TI  - Banking on approval. Regulators facing CON quandary.

PMID- 12195666
TI  - Diplomatic immunity. Smallpox safeguard for healthcare workers plagued by
      logistical issues.

PMID- 12195667
TI  - The Medicaid bind. Fiscally burdened states need short-term help, long-term fix
      for program.

PMID- 12195668
TI  - A new civil defense. Using powers dormant since '97, HHS' inspector general
      begins wielding civil monetary penalties as weapon in fight against fraud.

PMID- 12195669
TI  - Execs in the bonus round. Compensation survey data show strong gains among some
      senior healthcare executives, and top pay for top performance.

PMID- 12195671
TI  - Joint Commission takes stand on safety directives.

PMID- 12195670
TI  - End of an era. Justice Department ends nine-year criminal probe of Columbia/HCA
      executives, but company recovery began earlier.
AB  - The longest, costlest criminal healthcare fraud probe in U.S. history is finally
      over, but its ripple effects are likely to continue. The Columbia/HCA Healthcare
      Corp. case raised questions about healthcare accounting practices long before the
      current wave of corporate scandals. But the consensus is that the most crucial
      step in retooling HCA's image was restoring Thomas First Jr. (left) as chairman
      and CEO.

PMID- 12195672
TI  - Double jeopardy. Nyack Hospital shows investors set of restated financials, suit
      over accounting.

PMID- 12195673
TI  - China's biotech is starting to bloom.

PMID- 12195674
TI  - Hog wild for pollution trading.

PMID- 12195675
TI  - How I lost my chins.

PMID- 12195676
TI  - The next biohazard.

PMID- 12195677
TI  - Biting back. The West Nile virus and more-dangerous insect-carried relatives are
      in the U.S. to stay.

PMID- 12195678
TI  - The drug that could have been.

PMID- 12195679
TI  - The fire inside. A camp trains at-risk youth for homeland security jobs.

PMID- 12195680
TI  - A fat nation.

PMID- 12195681
TI  - The cosmic code. Does the universe run on a simple computer program?

PMID- 12195682
TI  - The gene that wouldn't sit still.

PMID- 12195683
TI  - A marine microbe maligned?

PMID- 12195684
TI  - Potentiation of fibrinolytic therapy in acute myocardial infarction: expanding
      the role of ACE-inhibitors.

PMID- 12195685
TI  - Coagulation factor interaction with platelets.

PMID- 12195686
TI  - Ramipril prior to thrombolysis attenuates the early increase of PAI-1 in patients
      with acute myocardial infarction.
AB  - In a placebo-controlled, double-blinded, randomized study we evaluated the effect
      of ramipril prior to thrombolysis on the course of PAI-1 plasma levels and on the
      frequency of postinfarct ischemic events in patients with acute myocardial
      infarction. Fifty-one out of 99 patients received 2.5 mg ramipril orally prior to
      thrombolysis and 12 h later. The blood samples for determination of PAI-1 plasma
      levels were collected on admission and 2, 4, 8, 12 and 24 h after thrombolysis.
      Postinfarct ischemic events were registered until coronary angiography was
      performed and defined as recurrent chest pain and/or evidence of ischemic signs
      on the ECG (ST-depression or ST-segment elevation of 1 mm in one or more inferior
      or anterior leads). Coronary angiography was performed within 7 days after the
      onset of myocardial infarction. Patients were classified into two groups: those
      without reperfusion of the infarct-related artery (TIMI grade 0 or 1) and those
      with reperfusion of the infarct-related artery (TIMI grade 2.3). On admission,
      PAI-1 plasma levels were similar in both groups (ramipril: 47.1 [4.8] ng/ml;
      placebo: 49.1 [4.8] ng/ml). The PAI-1AUC was 77.2 [6.7] ng/ml/h in the ramipril
      group and 95.4 [6.2] ng/ml/h in the placebo group (p = 0.013). Significant
      differences between groups were observed at 4, 8 and 12 h after thrombolysis (4
      h: 85.5 (11.3) vs. 116 (12.3) ng/ml, p < 0.01; 8 h: 79.1 (11.2) vs. 100.9 (9.3)
      ng/ml, p < 0.01; 12 hrs: 71.3 (9.5) vs. 87.4 (7.7) ng/ml, p < 0.05). The relative
      frequency of postinfarct ischemic events was significantly lower in the ramipril
      group (2.5% versus 7.1%, p = 0.001). Additionally, we observed a significant
      higher rate of TIMI grade 2 and 3 of the infarct-related artery in patients
      receiving oral ramipril compared to the placebo group (73% versus 54%; p =
      0.035). Our study demonstrates a favorable effect of ramipril on the fibrinolytic
      system after thrombolysis associated with a lower rate of postinfarct ischemic
      events within the first days after myocardial infarction. Therefore, the
      application of ramipril prior to thrombolysis appears to be a reasonable
      concomitant treatment which may reduce early infarct-related complications.

PMID- 12195687
TI  - Platelet activation and blood coagulation.
AB  - Platelet activation and blood coagulation are complementary, mutually dependent
      processes in haemostasis and thrombosis. Platelets interact with several
      coagulation factors, while the coagulation product thrombin is a potent platelet
      activating agonist. Activated platelets come in a procoagulant state after a
      prolonged elevation in cytosolic [Ca2+]i. Such platelets, e.g. when adhering to
      collagen via glycoprotein VI, expose phosphatidylserine (PS) at their outer
      surface and produce (PS-exposing) membrane blebs and microvesicles. Inhibition of
      aminophospholipid translocase and activation of phospholipid scramblase mediate
      the exposure of PS, whereas calpain-mediated protein cleavage leads to membrane
      blebbing and vesiculation. Surface-exposed PS strongly propagates the coagulation
      process by facilitating the assembly and activation of tenase and prothrombinase
      complexes. Factor IXa and platelet-bound factor Va support these activities. In
      addition, platelets can support the initiation phase of coagulation by providing
      binding sites for prothrombin and factor XI. They thereby take over the
      initiating role of tissue factor and factor VIIa in coagulation activation.

PMID- 12195688
TI  - The -33T-->C polymorphism in intron 7 of the TFPI gene influences the risk of
      venous thromboembolism, independently of the factor V Leiden and prothrombin
      mutations.
AB  - We have previously identified, in intron 7 of the TFPI gene, a T to C single-base
      polymorphism (-33T-->C) which is strongly associated with total circulating TFPI
      antigen levels. Here we examined the influence of this polymorphism on the risk
      of venous thromboembolism. The polymorphism was identified in the PATHROS study
      population (330 cases with venous thromboembolism and 826 controls). The CC
      genotype was found in 6.4% of cases and 10.2% of controls (age-adjusted odds
      ratio 0.6; 95% CI 0.3-0.9; p = 0.03). This protective effect persisted after
      adjustment for oral contraception and the factor V Leiden and prothrombin gene
      polymorphisms. In 171 controls and 49 cases in whom blood was taken at least
      three months after the thrombotic event, the CC genotype was associated with
      significantly higher total TFPI levels than the TT genotype. These results
      suggest that the CC genotype of the TFPI intron 7 polymorphism is an independent
      protective factor for venous thromboembolism, an effect probably mediated by
      increased TFPI levels.

PMID- 12195689
TI  - Electrical foot stimulation and implications for the prevention of venous
      thromboembolic disease.
AB  - BACKGROUND: Venous stasis caused by immobility is an important risk factor for
      deep vein thrombosis following surgery and lower limb trauma, in bed-ridden
      medical patients, and in high-risk long distance air travelers. A safe and
      convenient method for reducing venous stasis would be useful in patients while in
      hospital and after discharge during their rehabilitation. SUBJECTS AND METHODS:
      49 healthy subjects aged 51-76 were seated for 4 hours during which they received
      mild electrical stimulation of the calf, or sole of the foot (plantar muscles).
      Popliteal and femoral venous blood flow velocities were measured via doppler
      ultrasound. The non-stimulated lower extremity served as the simultaneous
      control. Subjects completed a questionnaire regarding their acceptance and
      tolerance of the electrical stimulation. RESULTS: There was a significant
      increase in venous femoral and popliteal blood flow for both calf (p < 0.035, p <
      0.003), and plantar muscles (p < 0.0001, p < 0.009) on the stimulated side
      compared to the unstimulated side. The magnitude of the effect was similar for
      calf and plantar muscle stimulation. Subjects did not find the experience
      uncomfortable, and would use an electrical stimulator if told by their physician
      that they were at risk for developing blood clots. CONCLUSIONS: Mild electrical
      stimulation of the feet, as well as the calf, is a safe effective and convenient
      method for counteracting venous stasis and therefore has the potential to reduce
      the risk of deep vein thrombosis and pulmonary embolism for subjects who are
      immobilized.

PMID- 12195690
TI  - Antipsychotic and antidepressant drug use in the elderly and the risk of venous
      thromboembolism.
AB  - BACKGROUND: Preliminary evidence suggests that use of antipsychotic drugs is
      associated with an increased risk of venous thromboembolism. OBJECTIVE: To
      evaluate the relationship between antipsychotic or antidepressant drug use and
      venous thromboembolism among adults aged 65 years and older. DESIGN:
      Retrospective cohort study using linked health care administrative databases over
      a nine year period. SETTING: The entire province of Ontario, Canada.
      PARTICIPANTS: Individuals aged 65 years and over exclusively prescribed either
      antipsychotic drugs (n = 22,514), antidepressant drugs (n = 75,649) or thyroid
      replacement hormones (33,033), the referent control group. We excluded those with
      an antecedent history of cardiovascular disease, venous thromboembolism or
      cancer, as well as those dispensed warfarin before study entry. MEASUREMENTS:
      Diagnosis of deep vein thrombosis or pulmonary embolism. RESULTS: Relative to
      those prescribed thyroid hormones, neither antidepressant (adjusted hazard ratio
      1.02, 95% CI 0.91-1.14) nor antipsychotic (adjusted hazard ratio 1.13, 95% CI
      0.96-1.32) drug use was associated with an increased risk for deep vein
      thrombosis. Similar risk estimates were found for deep vein thrombosis or
      pulmonary embolism. In a sub-group analysis, only butyrophenone use was found to
      be associated with a slightly increased risk of deep vein thrombosis (adjusted HR
      1.51, 95% CI 1.23-1.86) as well as deep vein thrombosis or pulmonary embolism
      (adjusted HR 1.43, 95% CI 1.18-1.74). CONCLUSIONS: In a large cohort of adults
      aged 65 years and older, neither antipsychotic or antidepressant drug use was
      associated with an increased risk of venous thromboembolism, with the exception
      of a slightly increased risk among those prescribed butyrophenones. Further data
      are required before use of these psychoactive drugs can be considered a risk
      factor for venous thromboembolism.

PMID- 12195691
TI  - Measurable differences between sequential and parallel diagnostic decision
      processes for determining stroke subtype: a representation of interacting
      pathologies.
AB  - Stroke diagnosis depends on causal subtype. The accepted classification procedure
      is a succession of diagnostic tests administered in an order based on prior
      reported frequencies of the subtypes. The first positive test result completely
      determines diagnosis. An alternative approach tests multiple concomitant
      diagnostic hypotheses in parallel. This method permits multiple simultaneous
      pathologies in the patient. These two diagnostic procedures can be compared by
      novel numeric criteria presented here. Thrombosis, a type of ischemic stroke,
      results from interaction between endothelium, blood flow and blood components. We
      tested for ischemic stroke on thirty patients using both methods. For each
      patient the procedure produced an assessment of severity as an ordered set of
      three numbers in the interval [0, 1]. We measured the difference in diagnosis
      between the sequential and parallel diagnostic algorithms. The computations
      reveal systematic differences: The sequential procedure tends to under-diagnose
      and excludes any measure of interaction between pathologic elements.

PMID- 12195692
TI  - Chemotherapy-induced activation of hemostasis: effect of a low molecular weight
      heparin (dalteparin sodium) on plasma markers of hemostatic activation.
AB  - PURPOSE: To evaluate the effect of standard chemotherapeutic regimens on the
      hemostatic profile of patients with breast and lung carcinoma; and to evaluate
      the effect of a single dose of a low molecular weight (LMW) heparin, dalteparin
      sodium, administered prior to the chemotherapy on markers of hemostatic
      activation. PATIENTS AND METHODS: 11 patients with breast cancer and 10 patients
      with lung cancer receiving systemic chemotherapy were studied. 10 breast cancer
      patients and 9 lung cancer patients completed at least 1 cycle of treatment and
      had all hemostatic studies. Patients had a complete hemostatic and prothrombotic
      profile performed at study initiation. Markers of hemostatic activation
      consisting of immunoassays for thrombin-antithrombin (TAT) complex and D-dimer
      were measured in plasma samples obtained prior to chemotherapy and at 1, 24 and
      48 h after treatment. A 2500 U dose of dalteparin was given prior to the 2nd
      cycle of chemotherapy; 5000 U of dalteparin was given prior to the 4th treatment
      cycle. RESULTS: Chemotherapy resulted in statistically significant increases in
      TAT and D-dimer for the 1, 24 and 48 h plasma samples in both the breast and lung
      cancer patients for all cycles of chemotherapy given without LMW heparin. There
      were statistically significant increases in basal thrombin generation over the 4
      cycles of treatment which was unrelated to active cancer. Both pretreatment doses
      of dalteparin effectively prevented increases in the markers of hemostatic
      activation. However, in the lung cancer patients, who had significantly increased
      basal thrombin generation, the 5000 U dose dalteparin was more effective.
      CONCLUSION: Chemotherapy results in significant hemostatic activation in patients
      with breast and lung cancer. The effect of treatment appears to be cumulative. A
      single dose of LMW heparin administered prior to therapy can suppress hemostatic
      activation.

PMID- 12195693
TI  - Von Willebrand factor modulates factor VIII immunogenicity: comparative study of
      different factor VIII concentrates in a haemophilia A mouse model.
AB  - The development of an immune response towards factor VIII (FVIII) remains the
      major complication of haemophilia A replacement therapy. Product-related risk
      factors have recently been identified on the basis of epidemiological studies,
      but the mechanism is not understood. To this end, various commercially available
      FVIII concentrates were administered by the IV route to FVIII-knockout mice and
      the resulting immune response was characterised. Significantly higher inhibitor
      titres (Bethesda assay) were observed for one recombinant FVIII and one plasma
      derived FVIII product depleted in von Willebrand factor (VWF). Inhibitor titres
      were reduced upon pre-incubation of FVIII with purified VWF. Epitope specificity
      of anti-FVIII IgG was characterised using FVIII-fragments produced in E. coli.
      Concentrates with no or reduced VWF-level elicited antibodies recognising
      predominantly the acidic a1 and a3 regions. Addition of VWF prior to injection
      also modified the epitope specificity. FVIII concentrates, therefore, show
      qualitative and quantitative variations in immunogenicity, which are at least
      partly modulated by VWF.

PMID- 12195694
TI  - Effect of homocysteine reduction by B-vitamin supplementation on markers of
      clotting activation.
AB  - Homocysteine may have an effect on risk of cardiovascular disease by stimulating
      procoagulant factors and/or impair anti-coagulant mechanisms or fibrinolysis.
      However, data in humans of such effects are sparse. In this intervention study,
      we examined the effect of homocysteine lowering by B-vitamin supplementation on
      prothrombin fragments 1 and 2 (F1 + 2), thrombin-antithrombin complex (TAT), and
      fibrin degradation products (D-dimer). The study comprised 118 healthy
      volunteers, 50 with homocysteine > 16 mumol/L and 68 with homocysteine < or = 16
      mumol/L, who were randomized to placebo or high-dose B-vitamin supplements (5 mg
      folic acid, 0.4 mg hydroxycobalamin, and 50 mg pyridoxine) daily for 8 weeks.
      Although homocysteine concentrations were 27.7% (p < 0.0001) reduced in the B
      vitamin group compared to the placebo group, no effect on F1 + 2 and TAT
      concentrations was observed. A 10.4% reduction was observed for D-dimer (p =
      0.08). In conclusion, it appears that in healthy subjects homocysteine reduction
      by B-vitamin supplementation has a modest beneficial effect on clotting
      activation.

PMID- 12195695
TI  - Reduced activation of the Gla19Ala FX variant via the extrinsic coagulation
      pathway results in symptomatic CRMred FX deficiency.
AB  - We characterized a symptomatic CRMred factor X (FX) deficiency produced by the
      Glu19Ala mutation in the gamma-carboxyglutamic-rich domain. FX activity levels in
      plasma were markedly reduced in prothrombin time assays (< 1-5%), whereas in
      activated partial thromboplastin assays (16%) and in RVV assays (17%) the
      reduction in activity mirrored that in antigen levels (17%). Activation of
      recombinant 19Ala-FX by factor IXa/factor VIIIa or RVV, and the activity in
      thrombin generation assays, were comparable to those of wild-type FX.
      Differently, complete activation of recombinant 19Ala-FX required a factor
      VIIa/TF concentration 30-fold higher than that of wild-type FX. The recombinant
      FVIIa significantly reduced PT values in 19Ala-FX reconstituted plasma, thus
      suggesting an alternative approach for treatment of FX deficiencies characterized
      by defective FX activation. The study of this FX deficiency provides an "in vivo"
      and "in vitro" model for the investigation of Gla domain interactions.

PMID- 12195696
TI  - Adverse effect of heparin on antithrombin action during endotoxemia:
      microhemodynamic and cellular mechanisms.
AB  - A recent clinical sepsis trial reported a significant reduction in 90-day
      mortality by antithrombin (AT) exclusively in the subgroup of patients without
      simultaneous heparin prophylaxis. Patients additionally receiving heparin did not
      benefit from AT treatment. Herein, we studied the microhemodynamic and cellular
      mechanisms of this adverse effect of heparin on AT actions by the use of
      intravital microscopy and granulocyte culturing. In Syrian golden hamsters
      normotensive endotoxemia was induced by 2 mg/kg endotoxin (LPS, E. coli) i.v. In
      a first group of animals, AT (AT, 250 IU/kg i.v., n = 6) was given 5 min before
      LPS administration. A second group of animals (Heparin + AT, n = 5) received AT
      (250 IU/kg i.v.) combined with unfractionated heparin (sodium heparin, 100
      IU/kg/24 h, i.v.). Additional animals (LMWH + AT, n = 5) received AT (250 IU/kg
      i.v.) combined with LMWH (nadroparin 47.5 IU anti-Xa/kg, s.c., 2 h before LPS).
      LPS-treated animals, which received only saline, served as controls (control, n =
      6). Using dorsal skinfold fold preparations, LPS-induced microvascular leukocyte
      endothelial cell interaction (LE) and alteration of functional capillary density
      (FCD) were studied by intravital video fluorescence microscopy. In controls, LPS
      induced a massive increase in LE with a maximum at 8 h and an impressive decrease
      in FCD over a 24-hour period. Both LPS effects were effectively prevented by AT
      treatment (p < 0.01), whereas Heparin + AT and LMWH + AT animals showed
      microcirculatory alterations comparable to that in controls. In additional in
      vitro chemotaxis assays. AT blocked neutrophil chemotaxis, an effect reversed by
      both unfractionated heparin and LMWH. Thus, our study elucidates a relevant in
      vivo and in vitro unfractionated heparin and LMWH adverse effect in the
      microcirculatory actions of AT during endotoxemia. These results indicate that
      heparin should be avoided to permit AT to modulate LPS-induced inflammatory
      responses.

PMID- 12195697
TI  - Inhibition of thrombin generation in plasma by fibrin formation (Antithrombin I).
AB  - The adsorption of thrombin to fibrin during clotting defines "Antithrombin I"
      activity. We confirmed that thrombin generation in afibrinogenemic or in
      Reptilase defibrinated normal plasma was higher than in normal plasma. Repletion
      of these fibrinogen-deficient plasmas with fibrinogen 1 (gamma A/gamma A), whose
      fibrin has two "low affinity" non-substrate thrombin binding sites, resulted in
      moderately reduced thrombin generation by 29-37%. Repletion with fibrinogen 2
      (gamma'/gamma A), which in addition to low affinity thrombin-binding sites in
      fibrin, has a "high affinity" non-substrate thrombin binding site in the carboxy
      terminal region of its gamma' chain, was even more effective and reduced thrombin
      generation by 57-67%. Adding peptides that compete for thrombin binding to fibrin
      [S-Hir53-64 (hirugen) or gamma'414-427] caused a transient delay in the onset of
      otherwise robust thrombin generation, indicating that fibrin formation is
      necessary for full expression of Antithrombin I activity. Considered together, 1)
      the increased thrombin generation in afibrinogenemic or fibrinogen-depleted
      normal plasma that is mitigated by fibrinogen replacement; 2) evidence that
      prothrombin activation is increased in afibrinogenemia and normalized by
      fibrinogen replacement; 3) the severe thrombophilia that is associated with
      defective thrombin-binding in dysfibrinogenemias Naples I and New York I, and 4)
      the association of afibrinogenemia or hypofibrinogenemia with venous or arterial
      thromboembolism, indicate that Antithrombin I (fibrin) modulates thromboembolic
      potential by inhibiting thrombin generation in blood.

PMID- 12195698
TI  - Distribution of endothelial cell protein C/activated protein C receptor (EPCR)
      during mouse embryo development.
AB  - The endothelial cell protein C receptor (EPCR) augments protein C activation by
      the thrombomodulin.thrombin complex. Deletion of the EPCR gene in mice has been
      reported to lead to embryonic lethality before embryonic day 10 (E10.0). To
      identify potential mechanisms responsible for this lethality, we performed an
      immunohistological analysis of EPCR distribution during mouse embryogenesis. EPCR
      was detected in the trophoblast giant cells at the feto-maternal boundary from
      E7.5 and at later time points in the trophoblasts of the placenta, suggesting a
      role in the haemostatic regulation of the maternal blood that irrigates these
      surfaces. In the embryo, EPCR was weakly detected in aortic endothelial cells
      from E13.5. Thereafter, EPCR levels increased in certain large blood vessels
      endothelial cells suggesting that the specificity of EPCR to large vessels is
      conferred in utero. However, not until postnatal day 7 did the intensity and
      distribution of EPCR staining mimic that observed in adult mice.

PMID- 12195699
TI  - Activated protein C inhibits lipopolysaccharide-induced tumor necrosis factor
      alpha production by inhibiting activation of both nuclear factor-kappa B and
      activator protein-1 in human monocytes.
AB  - Activated protein C (APC), an important natural anticoagulant, inhibits tumor
      necrosis factor-alpha (TNF-alpha) production and attenuates various deleterious
      events induced by lipopolysaccharide (LPS), contributing thereby to a significant
      reduction of mortality in patients with severe sepsis. In this study, we
      investigated the mechanism(s) by which APC inhibits TNF-alpha production by LPS
      stimulated human monocytes in vitro. Although APC inhibited LPS-induced TNF-alpha
      production in a concentration-dependent fashion, diisopropyl fluorophosphate
      treated APC, an active-site-blocked APC, had no effect. APC inhibited both the
      binding of nuclear factor-kappa B (NF-kappa B) to target sites and the
      degradation of I kappa B alpha. APC also inhibited both the binding of activator
      protein-1 (AP-1) to target sites and the activation of mitogen-activated protein
      kinase pathways. These observations strongly suggest that APC inhibited LPS
      induced TNF-alpha production by inhibiting the activation of both NF-kappa B and
      AP-1 and that the inhibitory activity of APC might depend on its serine protease
      activity. These results would at least partly explain the mechanism(s) by which
      APC reduces the tissue injury seen in animal models of sepsis and in patients
      with sepsis.

PMID- 12195700
TI  - Ciglitazone inhibits plasmin-induced proinflammatory monocyte activation via
      modulation of p38 MAP kinase activity.
AB  - Plasmin triggers chemotaxis and NF-kappa B- and AP-1-mediated proinflammatory
      gene expression in human peripheral monocytes (PM). Compared with macrophages and
      dendritic cells, PM express mainly the peroxisome proliferator-activated receptor
      (PPAR) gamma and traces of PPAR alpha as detected by semiquantitative RT-PCR and
      immunoblotting. The PPAR gamma agonist ciglitazone, but not the PPAR alpha
      agonist clofibric acid, concentration-dependently inhibited the plasmin-, but not
      the FMLP-induced PM chemotaxis. Similarly, release of interleukin (IL)-1 alpha,
      IL-1 beta and tumor necrosis factor (TNF)-alpha from plasmin-stimulated PM was
      concentration-dependently inhibited by ciglitazone, but not by clofibric acid,
      while the LPS-induced TNF-alpha release remained unaffected by any of both PPAR
      agonists. Ciglitazone activates PPAR gamma as shown by a novel surface plasmon
      resonance analysis and inhibits the plasmin-induced activation of NF-kappa B and
      AP-1. It also inhibits p38 MAPK phosphorylation essential for the plasmin-induced
      PM chemotaxis and gene activation. Thus, activation of PPAR gamma by ciglitazone
      may allow controLling of the plasmin-mediated recruitment and activation of PM at
      sites of inflammation.

PMID- 12195701
TI  - Effect of heparin on TAFI-dependent inhibition of fibrinolysis: relative
      importance of TAFIa generated by clot-bound and fluid phase thrombin.
AB  - Heparin has been proposed to enhance thrombolysis by inhibiting thrombin
      dependent generation of activated TAFI (thrombin activatable fibrinolysis
      inhibitor), a carboxypeptidase that inhibits fibrinolysis. We evaluated the
      effect of heparin in an in vitro thrombolysis model consisting of a radiolabelled
      blood clot submerged in defibrinated plasma. Fibrinolysis was induced by adding t
      PA (250 ng/ml) and calcium to the plasma bath. Control experiments indicated that
      thrombin generation induced by recalcification caused significant TAFI activation
      and inhibited clot lysis. Heparin (up to 1 U/ml), added to the plasma bath,
      failed to enhance clot lysis. Thrombin generation in the fluid phase was totally
      inhibited by heparin at concentrations > 0.5 U/ml. In contrast, thrombin
      generation on the clot surface was not inhibited by heparin (1 U/ml). TAFIa
      generation did occur in heparin-containing samples (1 U/ml) and amounted to about
      10% of TAFIa formed in control samples. This low amount of TAFIa did exert
      antifibrinolytic activity as indicated by the observation that the addition of a
      specific TAFIa inhibitor (PTI) along with heparin enhanced clot lysis. Hirudin
      (10 micrograms/ml), at variance with heparin, inhibited clot-bound thrombin and
      enhanced clot lysis. These data show that heparin is unable to stimulate
      fibrinolysis through a TAFI-dependent mechanism, most likely because of its
      inefficiency in inhibiting thrombin generation on the clot surface. Moreover,
      they suggest that clot-bound thrombin plays a major role in TAFI-mediated
      inhibition of fibrinolysis through "localized" TAFIa generation.

PMID- 12195702
TI  - Importance of N-terminal residues in plasminogen activator inhibitor 1 on its
      antibody induced latency transition.
AB  - The serpin plasminogen activator inhibitor-1 (PAI-1) is a well-known risk factor
      for thromboembolic and cardiovascular diseases. Many efforts have been made to
      reveal structure-function relationship in PAI-1, including the understanding of
      its unique latency transition. In this study, we describe the molecular
      characterization of PAI-1 neutralization by MA-159M12, a monoclonal antibody
      against rat PAI-1. Time-dependent inactivation of PAI-1, exposure of a trypsin
      cleavage site typically for the latent conformation and disappearance of elastase
      susceptibility revealed that MA-159M12 accelerated the active to latent,
      conformational transition (t1/2 120 +/- 12 min and 18 +/- 3.6 min in the absence
      and presence of MA-159M12, p < 0.0001). Cross-reactivity analysis of the antibody
      with various rat/human PAI-1 chimeras revealed that the epitope resides in alpha
      hA of rat PAI-1. Subsequent alanine-scanning mutagenesis and binding studies
      demonstrated that Pro2-Leu3-Pro4-Glu5 constitute the major residues of the
      epitope for MA-159M12. In conclusion, these findings demonstrate that, even
      though unexpected based on current knowledge on PAI-1 stability and function,
      interference with alpha hA results in a destabilisation of its active, inhibitory
      conformation. Therefore, alpha hA forms a putative target for the rational
      development of PAI-1 neutralizing components.

PMID- 12195703
TI  - A collaborative study to establish the 3rd International Standard for tissue
      plasminogen activator.
AB  - An international collaborative study was organised to replace the 2nd
      International Standard (IS) for tissue plasminogen activator (tPA). The 2nd IS
      for tPA (86/670) was used to calibrate the replacement Standard, which was
      selected from two candidate materials included in the collaborative study.
      Participants were provided with five sets of four samples (A, B, C, D) and asked
      to use sample A (2nd IS, 86/670, 850 IU/ml) to determine the activity of B
      (86/624, approximately 850 IU/ml), C and D (coded duplicates of the same
      material, 98/714 approximately 11,000 IU/ml). A total of 14 laboratories returned
      results from Europe, USA, Japan and Australia, providing data from 60 independent
      assays. Four laboratories used a reference method based on a published monograph
      from the European Pharmacopoeia for Alteplase for Injection, 1998, and the
      remaining 10 used their own method. Fibrin was used as promoter of tPA activity
      by 12 out of the 14 laboratories, the remaining two used kits where fibrinogen
      fragments were the promoter. Data from this collaborative study and the previous
      study to establish the 2nd IS for tPA show that tPA from melanoma cells and
      recombinant tPA from CHO cells are both suitable materials as International
      Standards. It was agreed that sample C, D, recombinant tPA, 98/714, be
      established as the 3rd International Standard for tPA with a potency of 10,000 IU
      per ampoule, calculated as the mean value from laboratories using fibrin as a
      promoter of tPA activity. The standard was established by WHO in November 2000.

PMID- 12195704
TI  - Metalloproteases cleave the urokinase-type plasminogen activator receptor in the
      D1-D2 linker region and expose epitopes not present in the intact soluble
      receptor.
AB  - Proteolytic cleavage of the urokinase plasminogen activator receptor (uPA(R))
      prevents the binding of uPA and vitronectin while generating biologically active
      uPAR fragments. We have recently shown that matrix metalloproteinase-12 (MMP-12)
      releases cellular uPAR-antigen from stimulated human micro-vascular endothelial
      cells providing a novel feedback mechanism between the plasminogen activation and
      MMP systems. We now show that MMP-12 and other MMPs directly and efficiently
      cleave uPAR at the Thr86 paralal Tyr87 peptide bond located in the linker region
      connecting uPAR domains 1 and 2, releasing the major ligand binding domain 1 from
      the rest of the receptor. The possible biological importance of uPAR cleavage by
      MMPs is supported by the observation that also murine uPAR is cleaved by MMP-12
      (at the Pro89 paralal Gln90 peptide bond), despite the limited sequence homology
      between the linker regions. Using an antibody raised against the human uPAR
      linker region we show that this region of uPAR, which contains the chemotactic
      SRSRY epitope, is exposed upon MMP cleavage.

PMID- 12195705
TI  - Transient platelet interaction induces MCP-1 production by endothelial cells via
      I kappa B kinase complex activation.
AB  - Activated platelets alter endothelial chemotactic and adhesive properties.
      Transient interaction of alpha-thrombin-activated platelets with endothelial
      cells is sufficient to induce secretion of the NF-kappa B-regulated chemokine MCP
      1. To evaluate upstream signaling events in platelet-induced NF-kappa B
      activation, we compared the effect of platelets, IL-1 beta or TNF-alpha on I
      kappa B kinase (IKK) complex activation and I kappa B
      phosphorylation/proteolysis. Kinase assays demonstrated that platelets induced a
      slow increase in IKK activity over 30 min, which was similar, but not identical,
      to IL-1 beta, whereas TNF-alpha elicited a rapid induction of IKK. Differential
      effects were also found on I kappa B-alpha/epsilon degradation, while IKK levels
      were unaffected. Furthermore, overexpression of kinase-inactive IKK-beta KA, as
      well as NIKKA, inhibited platelet- or IL-1 beta-induced kappa B-, MCP-1- or VCAM
      1-dependent transcription. Using adeno-associated virus particles for cell
      transduction, we found that IKK-beta KA substantially reduced stimulus-induced
      MCP-1 secretion. Platelet-induced signaling and resulting endothelial gene
      expression may play a role in early atherogenesis as well as plaque
      progression/destabilization.

PMID- 12195706
TI  - Intracellular factor XIII crosslinks platelet cytoskeletal elements upon platelet
      activation.
AB  - The platelet cytoplasm contains approximately half of the factor XIII (FXIII)
      transglutaminase content circulating in blood, yet the function of cytoplasmic
      FXIII is poorly understood. This study investigated functions of platelet FXIII
      in internal platelet processes by studying the interactions of FXIII with
      platelet cytoskeletal proteins. FXIII was present in cytoskeletal fractions of
      platelet lysate separated by centrifugation. When cytoskeletal fractions were
      immobilized on nitrocellulose membranes, thrombin-activated rFXIII (rFXIIIa*) or
      calcium ion-treated rFXIII (rFXIIIa degree) bound to some of these proteins,
      whereas untreated rFXIII did not. Utilizing fluorescence microscopy, an actin
      polymerization-dependent transient translocation of FXIII from a diffuse
      homogeneous distribution throughout the cytoplasm to the platelet periphery was
      observed upon platelet activation, suggesting an association with cytoskeletal
      proteins. Transglutaminase activity increased in cytoskeletal fractions of
      activated versus non-activated platelets. Immunoblotting analysis of platelet
      cytoskeletal fractions identified filamin and vinculin as being crosslinked upon
      platelet activation.

PMID- 12195707
TI  - Protease-activated receptors upregulate cyclooxygenase-2 expression in human
      endothelial cells.
AB  - We have previously shown that the serine protease thrombin and other G protein
      coupled agonists acutely enhance synthesis and release of prostacyclin from human
      umbilical vein endothelial cells (HUVEC) through activation of cPLA2 alpha. Here,
      we show that thrombin and other physiological endothelial cell agonists
      upregulate COX-2 induction in HUVEC. Thrombin treatment caused a rapid and
      sustained increase in prostacyclin (PGI2) synthesis from HUVEC. Thrombin and a
      selective protease-activated receptor-1 (PAR-1) peptide (TRAP) evoked dose- and
      time-dependent increases in COX-2 protein expression which were equivalent to
      that induced by the proinflammatory cytokine IL-1 alpha. Quantitative and real
      time PCR analysis showed enhanced COX-2 mRNA expression in thrombin- or TRAP
      stimulated HUVEC whereas COX-1 expression was unaffected. A PAR-2 agonist peptide
      also induced COX-2 protein and mRNA expression with kinetics distinct from those
      of thrombin, and promoted PGI2 release. These results demonstrate that regulation
      of COX-2 induction is an important functional response of HUVEC to PAR activation
      and suggest that PARs promote sustained upregulation of prostanoid production in
      human endothelium.

PMID- 12195708
TI  - Overexpression of fibrinogen in ApoE*3-Leiden transgenic mice does not influence
      the progression of diet-induced atherosclerosis.
AB  - Although many epidemiological studies have shown an association between
      hyperfibrinogenemia and atherosclerosis, it is not established whether elevated
      fibrinogen has an etiological role in the pathogenesis or is only a reflection of
      the ongoing disease. We have studied the contribution of fibrinogen to the
      development of atherosclerosis in atherosclerosis-prone ApoE*3-Leiden mice that
      have been cross-bred with transgenic mice overexpressing fibrinogen. Genetic
      compound offspring were used to evaluate the progression of atherosclerotic
      lesions after being fed an atherogenic diet for 7 weeks. It was observed that the
      lesion area of the plaques as well as the severity of the lesions in the aortic
      valve was comparable in control single transgenic ApoE*3-Leiden mice and in
      double transgenic apoE*3-Leiden mice overexpressing fibrinogen. No thrombus or
      fibrin deposition was observed in atherosclerotic lesions in either group of
      mice. These results indicate that elevated plasma fibrinogen concentrations in
      ApoE*3-Leiden transgenic mice do not affect the progression of diet-induced
      atherosclerotic lesions.

PMID- 12195709
TI  - Quenching of intracellular ROS generation as a mechanism for oleate-induced
      reduction of endothelial activation and early atherogenesis.
AB  - We previously showed that the exposure of vascular endothelium to oleate results
      in reduced endothelial activation. We now investigate possible mechanisms for
      this effect in relation to generation of reactive oxygen species (ROS). We
      stimulated several types of endothelial cells with cytokines or
      lipopolysaccharide, with or without preincubation with 10-100 mumol/L oleate.
      Oleate preincubation reduced VCAM-1 expression in all cell types, as well as
      macrophage-colony stimulating factor release. We simultaneously measured the
      concentration of intracellular glutathione (GSH), the activity of GSH-related
      antioxidant enzymes and the production of intracellular ROS. Stimulation of
      endothelial cells caused a decrease of GSH and an increase in intracellular ROS.
      The addition of oleate before stimulation, prevented the depletion of GSH and
      partially prevented stimuli-induced increase of intracellular ROS. This occurred
      without any change in the activity of GSH-related antioxidant enzymes, superoxide
      dismutase and catalase. Furthermore, in a cell-free superoxide anion-generating
      system, oleate quenched the generation of ROS. These results indicate that oleate
      may exert direct vascular atheroprotective effects by inhibiting endothelial
      activation through a quenching of stimuli-induced increase in ROS.

PMID- 12195710
TI  - Modulation of fibrinolytic and gelatinolytic activity during adipose tissue
      development in a mouse model of nutritionally induced obesity.
AB  - A nutritionally induced obesity model was used to investigate the modulation of
      fibrinolytic and gelatinolytic activity during the development of adipose tissue.
      Five week old male mice were fed a standard fat diet (SFD, 13% kcal as fat) or a
      high fat diet (HFD, 42% kcal as fat) for up to 15 weeks. The HFD resulted in body
      weights of 31 +/- 0.9 g, 38 +/- 2.0 g and 47 +/- 1.9 g at 5, 10 and 15 weeks,
      respectively; corresponding values for mice on the SFD were 26 +/- 0.6 g, 31 +/-
      0.9 g and 31 +/- 1.2 g (all p < 0.001). The weight of the isolated subcutaneous
      (s.c.) or gonadal (GON) fat after 15 weeks of HFD was 1,870 +/- 180 mg or 1,470
      +/- 160 mg, as compared to 250 +/- 58 mg or 350 +/- 71 mg for the SFD (p <
      0.001). The HFD induced marked time-dependent hyperglycemia and elevated levels
      of triglycerides and total cholesterol. The HFD diet also induced a marked
      hypertrophy of the adipocytes as compared to the SFD, e.g. diameter of 83 +/- 3.0
      microns versus 52 +/- 4.2 microns for GON adipocytes at 15 weeks (p < 0.005).
      Plasma plasminogen activator inhibitor-1 (PAI-1) levels were higher in mice on
      the HFD as compared to the SFD; they were comparable in extracts of s.c. or GON
      adipose tissue, whereas at different time points tissue-type (t-PA) and urokinase
      type (u-PA) plasminogen activator activity was somewhat lower in the adipose
      tissues of mice on HFD. Gelatinolytic activity (mainly MMP-2) was detected in
      s.c. but not in GON adipose tissue of mice on SFD, and decreased on the HFD. In
      situ zymography on cryosections did not reveal different fibrinolytic activities
      in s.c. or GON adipose tissues of the HFD as compared to the SFD groups, whereas
      significantly lower gelatinolytic and higher caseinolytic activities were
      detected in s.c. and GON tissues of mice on the HFD (p < or = 0.05). The
      fibrillar collagen content was lower in adipose tissue of mice on HFD. Thus, in
      this model time-dependent development of adipose tissue appears to be associated
      with modulation of proteolytic activity.

PMID- 12195711
TI  - Effect of factor XIII VAL34LEU polymorphism on thrombolytic therapy in premature
      myocardial infarction.

PMID- 12195712
TI  - cDNA cloning and tissue distribution of the rat ortholog of tissue factor pathway
      inhibitor-2.

PMID- 12195713
TI  - 11 hemophilia A patients without mutations in the factor VIII encoding gene.

PMID- 12195714
TI  - Inhibition of human osteoblast growth by unfractionated heparin and by low
      molecular weight heparins in vitro.

PMID- 12195715
TI  - A 4% solution of bovine serum albumin may be used in place of factor VIII:C
      deficient plasma in the control sample in the Nijmegen Modification of the
      Bethesda factor VIII:C inhibitor assay.

PMID- 12195716
TI  - Reduced collagen-induced platelet aggregation in obligate heterozygotes of a
      Glanzmann thrombasthenia variant with a beta 3 mutation.

PMID- 12195717
TI  - Influence of the risk factors for atherosclerosis on levels of soluble adhesion
      molecules and endothelial markers in peripheral vascular disease.

PMID- 12195718
TI  - Relationship between C-5T Kozak, C807T genotypes and expression of glycoproteins
      Ib alpha and Ia-IIa at platelet surface: from genotype to phenotype.

PMID- 12195719
TI  - Relationship between ABCA1 genetic variation and HDL cholesterol level in
      subjects with ischemic heart diseases in Japanese.

PMID- 12195720
TI  - Perinatal management of patients at high risk of homozygous protein C deficiency.

PMID- 12195721
TI  - Heparin-platelet factor 4 induced antibodies in patients with either autoimmune
      or alloimmune antiphospholipid antibodies.

PMID- 12195722
TI  - One reader's expectation of a commentary.

PMID- 12195723
TI  - What can we learn from the immune response to human factor VIII in a mouse model
      of hemophilia A?

PMID- 12195725
TI  - Determination of lead in whole blood: comparison of the LeadCare blood lead
      testing system with Zeeman longitudinal electrothermal atomic absorption
      spectrometry.
AB  - This study compares the efficiency of blood lead level analysis by graphite
      furnace atomic absorption spectrometry (GFAAS) and the portable LeadCare Blood
      Lead Testing System (LCS). Recoveries of two added lead concentrations of 22 and
      42 micrograms/dL ranged from 102.4 to 105.5% for LCS and from 96.3 to 97.2% for
      GFAAS. Measurement of a certified sample (Certified Danish Whole Blood) at a
      blood lead concentration of 26.2 micrograms/dL gave within- and between-run
      coefficients of variation which were both approximately 8% by LCS and 2% by
      GFAAS. Comparison of the tested method (LCS) versus GFAAS from analysis of 76
      samples of blood lead collected from workers in different industrial sectors
      showed imperfect overall correlation (r = 0.95). The LCS is quite suitable for
      screening purposes, but requires the use of non-frozen blood collected less than
      24 h before. Conservative threshold values should be applied when using the LCS
      for initial screening in the field.

PMID- 12195724
TI  - Determination of some cationic species in temporary teeth.
AB  - Some cationic species (Ca, Mg, Sr, Cu, Zn and Pb) have been determined in
      temporary teeth (n = 67) sampled from a children population living in Merida,
      Venezuela, with a mean age of 87.76 +/- 34.50 months within a range from 29 to
      151 months. Each powdered tooth sample was analyzed for calcium, magnesium,
      strontium and zinc and for copper and lead by atomic absorption spectrometry with
      flame and electrothermal atomization, respectively. Relations between variables
      (elements concentration, age, sex, tooth type and caries status) were established
      using the Pearson correlation matrix and analysis of variance. The mean global
      concentrations were of 39.25 +/- 5.36; 1.08 +/- 0.81; 89.27 +/- 13.26 and 2.85 +/
      1.14 micrograms/g for Sr, Cu, Zn and Pb and of 208.45 +/- 33.18 and 8.51 +/-
      2.05 mg/g for Ca and Mg, respectively. There were no changes in the teeth mineral
      content with respect to the children age and sex. With respect to the tooth type,
      there were significant differences only for strontium which varied in the order
      molars > canines > incisors. Although healthy teeth had higher mineral
      concentrations than carious teeth, there were not significant differences,
      proving that both, carious and healthy teeth could be used as indicators of
      mineral uptake. Magnesium and copper are the elements least related with the
      others. Significant positive correlations were found between Sr-Zn, Sr-Cu, Sr-Pb,
      and the only negative correlations were between Ca-Zn and Ca-Pb for the different
      types of teeth. While the positive association might indicate competition for
      anionic groups or similar affinity for the same sites in the crystalline
      structure, the negative correlations showed possible substitutions among the
      elements.

PMID- 12195726
TI  - Testicular zinc, copper and iron concentrations in male rats exposed to subacute
      and subchronic formaldehyde gas inhalation.
AB  - The level of trace elements such as Zn, Cu and Fe in testicular tissue is an
      indication of the condition of the tissue as these elements take over important
      tasks. Zinc and copper are the prosthetic groups of several metalloenzymes
      including superoxide dismutase (SOD) which is an important antioxidant enzyme in
      the cellular protection from reactive oxygen species. If concentrations of these
      trace elements decrease significantly, SOD cannot detoxify harmful oxygen
      species. In this study, adult male rats (wistar-albino) were exposed to
      formaldehyde at different periods (subacute and subchronic) and concentrations
      (0; 12.2; 24.4 mg.L-1). Body and testis weights were recorded and compared with
      control groups. The metals described above were determined in rat testicular
      tissue by atomic absorption spectrometry by using wet ashing. We conclude that
      subacute or subchronic exposure to formaldehyde have caused growth retardation
      and altered levels of trace elements, including copper, zinc and iron, in
      testicular tissue, and may induce further oxidative damage on testicular tissue
      leading to spermatozoal abnormalities.

PMID- 12195727
TI  - Selenium serum and urine is associated to mild asthma and atopy. The SUS study.
AB  - To examine the associations between selenium (Se) status, asthma, bronchial
      hyperresponsiveness (BHR), and atopy in 154 male subjects (72 with mild asthma,
      41 with BHR and 41 with no respiratory symptoms) aged 18 (range 17-22) years.
      Each subject underwent a medical interview and FEV1 and FVC were recorded.
      Histamine bronchial reactivity (Yan method) was measured, skin prick test
      (inhalant allergens) was performed and Se in urine and serum was analysed (AOAC
      modified fluometric method). Se in serum 74.04 (10.58) micrograms/L (mean (SD))
      was lower in subjects with asthma and the logarithm of the ratio of Se in serum
      (microgram/L) and urine standardised to creatinine excretion (ng/mg creatinine)
      0.748 (0.096) (mean (SD)) was lower in subjects with asthma and atopy compared to
      subjects with no allergic symptoms 77.79 (10.16) micrograms/L and 0.808 (0.111)
      respectively (p < 0.05). In subjects with asthma atopy was significantly
      associated to urine Se 0.24 (0.73) (beta (SE)) (p < 0.05). Subjects with BHR had
      the same Se status as subjects with no respiratory symptoms and heavy smokers had
      a lower concentration of Se in serum 73.80 (9.56) micrograms/L than non-smokers
      78.16 (10.74) micrograms/L (p < 0.05), Se status was associated to asthma and
      smoking. Measuring Se in urine might add further information to possible
      relations between Se status, atopy and asthma.

PMID- 12195728
TI  - Zinc supplementation does not inhibit basal and metoclopramide-stimulated
      prolactinemia secretion in healthy men.
AB  - Dopamine (DA) and zinc (Zn++) share common mechanisms in their inhibition of
      prolactin (PRL) secretion. Both substances are present in the same brain areas,
      where Zn++ is released together with DA, suggesting a modulatory effect of Zn++
      on dopaminergic receptors. The aim of the present study was to evaluate the
      effect of Zn++ supplementation on basal and PRL secretion stimulated by
      metoclopramide (MCP), a dopaminergic antagonist. Seven healthy men were evaluated
      in controlled study, where MCP (5 mg) was given intravenously, before and after 3
      months of oral Zn++ (25 mg) administration. Our results indicate that chronic
      Zn++ administration does not change basal or MCP-stimulated plasma PRL secretion
      suggesting that, in humans, Zn++ does not interfere on PRL secretion mediated
      through dopaminergic receptors.

PMID- 12195729
TI  - Serum copper and zinc concentrations in a representative sample of the Canarian
      population.
AB  - Serum copper (Cu) and zinc (Zn) concentrations of 395 individuals (187 males +
      208 females) living in Canary Islands were determined by flame atomic absorption
      spectrometry. The mean copper and zinc concentrations were 1.10 +/- 0.25 mg/L and
      1.16 +/- 0.52 mg/L respectively. Our data were similar to other data published in
      other Spanish regions. Individuals from Lanzarote presented a mean Cu and Zn
      concentrations higher (p < 0.05) than individuals from the rest of islands;
      Individuals from EL Hierro showed the lowest (p < 0.05) mean Zn concentration.
      These differences could be attributed a differences in Cu and Zn contents of soil
      and/or differences in dietary habits of the populations. The mean serum Cu
      concentration in females was higher (p < 0.05) than in males, however serum Zn
      concentration did not vary with the sex of the subjects. No relation to socio
      economic status and educational level were found with respect to the serum Cu and
      Zn concentrations. The serum Cu concentration varied with age of individuals,
      observing the highest (p < 0.05) Cu concentration in the 20-30 year old interval.
      A higher serum Cu concentration in females within 20-30 year old interval was
      observed. This could be due to a higher use of oral contraceptives or to the
      higher number of pregnancies. Boys (younger than 15) showed a decrease (p < 0.05)
      of the serum Cu concentration with age. The mean Zn concentrations in serum did
      not change (p > 0.05) among the different age intervals. No clear trends in the
      serum Cu and Zn concentrations were observed when drinking and smoking habits
      were considered. The increase of physical exercise reduced (p < 0.05) the serum
      Cu concentrations.

PMID- 12195730
TI  - Relationship of dietary intake of fish and non-fish selenium to serum lipids in
      Japanese rural coastal community.
AB  - Several studies have suggested that dietary selenium deficiency may be associated
      with an increased risk of coronary heart disease (CHD). In the present study, 55
      men and 71 women were selected from participants in a health examination in a
      rural coastal community in Japan. The mean dietary selenium intake calculated
      from the simple food frequency questionnaire (SFFQ) was 127.5 micrograms/day.
      Fish was the major source of dietary selenium and it contributed to 68.7% of the
      daily total. HDL cholesterol was higher in the middle selenium intake group and
      in the high selenium intake group than in the low selenium intake group in all
      subjects and for males, and a significant difference was found between the middle
      selenium intake group and the low selenium intake group. The atherogenic index
      was significantly higher in the low selenium intake group than in the middle
      selenium intake group and in the high selenium intake group in males. GPx
      activity, total cholesterol and triacylglycerols did not show any significant
      differences among the three different selenium intake groups. Dietary intake of
      non-fish Se had a positive correlation with HDL cholesterol, and an inverse
      correlation with the atherogenic index in all subjects and for females. On the
      other hand, dietary intake of fish-Se had no relationship with any serum lipids.
      Non-fish Se is an important factor in selenium status for the prevention of CHD.

PMID- 12195731
TI  - Effects of lithium carbonate on hematopoietic cells in patients with persistent
      neutropenia following chemotherapy or radiotherapy.
AB  - Neoplasm therapy is restricted by the haematological side effects of tumour
      destructive therapy, requiring expensive supportive care to some extent to
      overcome and treat leucopenia and its consequences. An effective and very cost
      effective alternative for treating neutropenia is to administer lithium
      carbonate. Lithium leads to a release of hematopoietic growth factors (CSF) and
      therefore to proliferation of neutrophil granulocytes. Normally, recombinant CSF
      is only administered when there are indications of severe neutropenia because of
      the high costs involved, all the more evident in the long-term treatment of
      persistent leucocytopenia. On the other hand, CSF and leucocytes play an
      essential role in tumour immunology and with regard to response rates to
      cytostatic drugs. Lithium salts have shown that they can increase the number of
      neutrophil granulocytes quite significantly and, to a lesser extent, the number
      of eosinophil granulocytes and lymphocytes as well. The average number of
      erythrocytes does not change significantly. Patient tolerability to lithium
      carbonate therapy is very good. It can be used to treat patients with chronic
      leucopenia following chemotherapy or radiotherapy extremely cost-effectively.
      Unfortunately this treatment has not won acceptance in clinical oncology in the
      face of highly cost-intensive treatment with recombinant CSF.

PMID- 12195732
TI  - Preliminary investigation on the cytotoxicity of tellurite to cultured HeLa
      cells.
AB  - Cytotoxicity of tellurite to cultured HeLa cells was examined by cell viability,
      lactate dehydrogenase (LDH) assay, and tellurite uptake. The experimental results
      show that the toxicity of tellurite depends on its concentrations and exposure
      time. HeLa cells exposed to tellurite for 2 h at 9.1 x 10(-4) to 4.5 x 10(-3)
      mmol/L did not exhibit cytotoxic effects as measured by cell viability. Exposure
      to tellurite for 24 h at the same concentrations markedly reduced the cell
      viability to 57% of the control during the first 5 minutes. Additionally, HeLa
      cells incubated at 2.7 x 10(-2) to 0.27 mmol/L of tellurite for 2 h retained 53%
      to 67% of cell viability. Even after 24 h exposure, the HeLa cells incubated at
      9.1 x 10(-4) to 4.5 x 10(-2) mmol/L of tellurite still retained 57% to 66% of
      cell viability. Furthermore, tellurite toxicity was also demonstrated in
      supernatant of the culture at 37 degrees C by LDH assay. It was found that
      exposure to tellurite for 90 minutes did not stimulate LDH activity. However,
      tellurite uptake seems to be more sensitive than the cell viability and LDH
      activity release tests, as it significantly increases with the increasing of
      exposure time.

PMID- 12195733
TI  - Mechanisms of antibiotic resistance in bacterial biofilms.
AB  - Bacteria that attach to a surface and grow as a biofilm are protected from
      killing by antibiotics. Reduced antibiotic susceptibility contributes to the
      persistence of biofilm infections such as those associated with implanted
      devices. The protective mechanisms at work in biofilms appear to be distinct from
      those that are responsible for conventional antibiotic resistance. In biofilms,
      poor antibiotic penetration, nutrient limitation and slow growth, adaptive stress
      responses, and formation of persister cells are hypothesized to constitute a
      multi-layered defense. The genetic and biochemical details of these biofilm
      defenses are only now beginning to emerge. Each gene and gene product
      contributing to this resistance may be a target for the development of new
      chemotherapeutic agents. Disabling biofilm resistance may enhance the ability of
      existing antibiotics to clear infections involving biofilms that are refractory
      to current treatments.

PMID- 12195734
TI  - The role of integrons in antibiotic resistance gene capture.
AB  - Although recently discovered, integrons have played a primordial role in the
      evolution of bacterial genomes. They are best known as the genetic agents
      responsible for the capture and spread of antibiotic resistance determinants
      among diverse Gram-negative clinical isolates, and this activity is at the root
      of the antibiotic resistance phenomenon that has evolved over the last 60 years.
      The discovery of the ancestral chromosomal super-integrons, novel integron
      classes, and the multitude of gene cassettes they propagate solidify the crucial
      role of this system in adaptive bacterial evolution. Recent evidence suggests
      that evolutionarily old genetic recombination mechanisms for gene transfer have
      been adapted to the new antibiotic environment due to the heavy selective
      pressure of liberal antibiotic use in human medicine and animal husbandry.

PMID- 12195736
TI  - The molecular basis of antibiotic resistance: where Newton meets Darwin.

PMID- 12195735
TI  - Molecular analysis of beta-lactamase structure and function.
AB  - The extensive and sometimes irresponsible use of beta-lactam antibiotics in
      clinical and agricultural settings has contributed to the emergence and
      widespread dissemination of antibiotic-resistant bacteria. Bacteria have evolved
      three strategies to escape the activity of beta-lactam antibiotics: 1) alteration
      of the target site (e.g. penicillin-binding protein (PBPs), 2) reduction of drug
      permeation across the bacterial membrane (e.g. efflux pumps) and 3) production of
      beta-lactamase enzymes. The beta-lactamase enzymes inactivate beta-lactam
      antibiotics by hydrolyzing the peptide bond of the characteristic four-membered
      beta-lactam ring rendering the antibiotic ineffective. The inactivation of the
      antibiotic provides resistance to the bacterium. Currently, there are over 300
      beta-lactamase enzymes described for which numerous kinetic, structural,
      computational and mutagenesis studies have been performed. In this review, we
      discuss the recent work performed on the four different classes (A, B, C, and D)
      of beta-lactamases. These investigative advances further expand our knowledge
      about these complex enzymes, and hopefully, will provide us with additional tools
      to develop new inhibitors and antibiotics based on structural and rational
      designs.

PMID- 12195737
TI  - Molecular genetics of methicillin-resistant Staphylococcus aureus.
AB  - A large and growing proportion of Staphylococcus aureus clinical isolates are
      methicillin resistant, and are resistant to practically all beta-lactam
      antibiotics. Methicillin-resistant S. aureus (MRSA) strains harbor mecA, which is
      carried by a unique mobile genetic element, staphylococcal cassette chromosome
      mec (SCCmec) integrated into the S. aureus chromosome. The mecA gene encodes a
      methicillin-insensitive transpeptidase, the production of which confers
      resistance to otherwise inhibitory concentrations of beta-lactam antibiotics.
      Several distinct clones have been identified among MRSA that apparently have been
      generated by integration of distinct types of SCCmec. While MRSA are primarily
      nosocomial pathogens, recent observations indicate that other MRSA clones are
      colonizing a significant proportion of healthy individuals in the community as
      well. Community-acquired MRSA (C-MRSA), may become a new threat to humans, and
      international cooperation of researchers and clinicians will be of cardinal
      importance in addressing this problem.

PMID- 12195738
TI  - Molecular analysis of antibiotic tolerance in pneumococci.
AB  - Widespread pneumococcal resistance and the emergence of tolerance underscores the
      need to develop new antimicrobials. Uncovering the mechanisms of autolysin
      activation could yield not only new antibacterial targets but also ways to
      eradicate a pool of bacteria facilitating the spread of resistance. Although
      several genes contributing to antibiotic tolerance among pneumococci have been
      identified, those important in the clinical arena thus far are in a single gene
      cluster, vex/pep27/vncS/vncR. Mutations within this signal transduction system
      represent at least one mechanism, which explains tolerance to both penicillin and
      vancomycin. Since mutations in this locus do not result in tolerance to
      penicillin alone, there must be other, yet unknown, mutations which account for
      tolerance to a single antibiotic. In the case of pneumococci, there exist two
      more autolysins other than LytA suggesting our understanding of how bacteria die
      is currently only at the beginning.

PMID- 12195739
TI  - Molecular analysis of streptogramin resistance in enterococci.
AB  - The new semi-synthetic streptogramin antibiotic combination
      quinupristin/dalfopristin (Synercid) is a promising alternative for a treatment
      of infections with multiple resistant gram-positive pathogens, e.g. glycopeptide-
      and multi-resistant Enterococcus faecium. Streptogramins consist of two unrelated
      compounds, a streptogramin A and B, which act synergistically when given in
      combination. Mechanisms conferring resistance against both components are
      essential for resistance against the combination in E. faecium. In this species
      resistance to streptogramin A compounds is mediated via related
      acetyltransferases VatD and VatE. Resistance against streptogramins B is either
      encoded by the widespread ermB gene cluster conferring resistance to macrolide
      lincosamide-streptogramin B antibiotics or via expression of the vgbA gene, which
      encodes a staphylococcal-type lactonase. E. faecalis is intrinsically resistant
      to streptogramins. Due to a wide use of streptogramins (virginiamycins S/M) in
      commercial animal farming a reservoir of streptogramin-resistant E. faecium
      isolates had already been selected. Determinants for streptogramin resistance are
      localized on plasmids that can be transferred into an E. faecium recipient both
      in vitro in filter-matings and in vivo in the digestive tracts of rats.
      Hybridization and sequencing experiments revealed a linkage of resistance
      determinants for streptogramins A and B on definite plasmid fragments.

PMID- 12195741
TI  - Quality-of-life assessment in oncology. Achievements and challenges.
AB  - In this article important areas of health-related quality of life (HRQL) research
      and major achievements are described, illustrated by studies conducted with
      cancer patients. Some of the challenges facing this line of research are
      elucidated. The areas of HRQL research described are distinguished according to
      their intended objective, including research aimed to assess treatment outcome
      and/or to qualify rates of survival, to assess late problems, to predict
      mortality, and to support information-giving. It was found that HRQL assessments
      are useful in clinical trials and cost-effectiveness studies and that they point
      to areas where former cancer patients may experience serious problems. It was
      also found that HRQL data are strong predictors of survival. Finally, HRQL
      assessments were found to stimulate doctor-patient communication. Three
      challenges are discussed, including the use of proxy respondents, the need to
      take response shift into account, and the interpretation of HRQL results as
      clinically meaningful. New research areas, such as HRQL related to genetic
      testing and as experienced by ethnic minorities urgently need to be taken on.

PMID- 12195740
TI  - Molecular analysis of efflux pump-based antibiotic resistance.
AB  - Multidrug efflux transporters are normal constituents of bacterial cells. These
      transporters are major contributors to intrinsic resistance of bacteria to many
      anti-microbial agents. In clinical settings, exposure to antibiotics promotes the
      mutational overexpression of active or silent multidrug transporters, leading to
      increased antibiotic resistance without acquisition of multiple, specific
      resistance determinants. The paradoxical ability of multidrug transporters to
      recognize and efficiently expel from cells scores of dissimilar organic compounds
      has been in the focus of extensive research for many years. Several independent
      studies implied that the mechanistic basis of such ability lies in a distinctive
      locus of the transporter-substrate interaction: the multidrug transporters select
      and bind their substrates within the phospholipid bilayer. The recently reported
      high-resolution structure of a complete MsbA transporter of Escherichia coli
      provides a solid structural basis for these studies. Although the majority of
      multidrug transporters function as single-component pumps, major transporters of
      Gram-negative bacteria are organized as three-component structures. Special outer
      membrane channels and periplasmic proteins belonging to the membrane fusion
      protein family enable drug efflux across a Gram-negative two-membrane envelope,
      directly into the external medium. This minireview focuses on the current status
      of research in the field of multidrug efflux mechanisms.

PMID- 12195742
TI  - Psychological intervention. The gap between research and practice.
AB  - Despite a substantial body of literature on psychological interventions for
      cancer patients, there is a death of psycho-oncology units where such
      interventions can be conducted in Britain. For the majority of cancer patients,
      systematic psychological therapy is not available. Is such therapy of benefit to
      patients? The literature reveals compelling evidence from randomized trials that
      patients' quality of life can be improved significantly by psychological
      interventions, in particular cognitive behavioural therapy, psychoeducational
      therapy and supportive-expressive group therapy. Evidence concerning the effect
      of psychological interventions on survival is contradictory. But irrespective of
      that question, since cancers are chronic diseases, quality of life is important
      to patients; hence every effort should be made to provide facilities for evidence
      based psychological interventions. One psychological factor shown to have a
      significant detrimental effect on both quality of life and survival of cancer
      patients is the coping response of helplessness/hopelessness. This response can
      be altered by psychotherapy.

PMID- 12195743
TI  - Symptom documentation in cancer survivors as a basis for therapy modifications.
AB  - In order to suggest therapy modifications with the aim of diminishing the risk of
      therapy-induced long-term distressful symptoms in cancer survivors, data are
      needed relating details of therapy to the long-term symptom situation. In this
      article, the concepts and means used to assess the latter while developing the
      Radiumhemmet scale for symptom assessment are described. The focus is on the
      subjective long-term situation, and symptoms as a perceived abnormality are
      defined. For conceptual clarity, one symptom at a time is considered, excluding
      scales in which items are summarized. Moreover, measures of disease occurrence in
      the population are translated (epidemiologically) into measures of symptom
      occurrence in an individual. Nature distinguishes one long-term symptom from
      another. Occurrence of a symptom in an individual is measured by an incidence
      (e.g. number of defecations per week) or prevalence rate (e.g. urinations with
      involuntary cessation divided by the total number of urinations). Any scale
      expressing symptom intensity is arbitrary, be it 'verbal'
      (no/little/moderate/much pain) or visual (analogue or with integers). A time
      period describes symptom duration. The relevance of a symptom to emotions and
      social activities, sometimes cited as the associated symptom-induced distress, is
      a separate issue from symptom occurrence, intensity, and duration.

PMID- 12195744
TI  - Quality of care from a patient perspective in population-based cervical cancer
      screening.
AB  - In Stockholm, population-based cervical cancer screening is offered free of
      charge to all women between 23 and 60 years of age. A survey to assess
      satisfaction with care using a previously validated questionnaire was conducted
      with 73 women receiving abnormal Pap smear results through the screening program.
      Thirty-seven women received results of screening within a feasibility project, in
      which they had extra contact with a midwife prior to receiving standard
      information and medical follow-up by a gynaecologist. The other 36 women were a
      matched sample receiving standard information. The results indicate generally
      high perceptions of quality of care, with particularly high ratings of perceived
      gynaecological knowledge and medical information provision. Low perceptions of
      quality were found regarding several aspects of psychosocial care. Higher levels
      of self-reported psychological well-being were found among the women who had
      extra midwifery contact. The results indicate that more attention to psychosocial
      aspects might optimize the screening program.

PMID- 12195745
TI  - A longitudinal study of the Swedish Self-Evaluation of Communication Experiences
      after Laryngeal Cancer questionnaire in patients treated for laryngeal cancer.
AB  - A prospective longitudinal study was performed to investigate the sensitivity to
      change over time of the Swedish Self-Evaluation of Communication Experiences
      after Laryngeal Cancer questionnaire (S-SECEL), addressing communication
      dysfunction in patients with laryngeal cancer. Twenty-six consecutive patients
      attending a weekly tumour conference over a period of one year at Sahlgrenska
      University Hospital were included in the study prior to start of treatment. The
      patients answered four questionnaire repeatedly in the course of one year: the S
      SECEL, the European Organization for Research and Treatment of Cancer (EORTC),
      the Core Quality of Life Core Questionnaire (QLQ-C30) supplemented by the Head
      and Neck cancer questionnaire module (QLQ-H&N35), and the Hospital Anxiety and
      Depression (HAD) scale. In addition, performance status was assessed. The S-SECEL
      questionnaire was well accepted by the patients, and compliance was satisfactory
      with a cumulative response rate of 88% at one year, supporting its feasibility in
      clinical settings. Repeated measures with the S-SECEL over one year demonstrated
      a significant decrease in voice and speech dysfunction. The correlation pattern
      over time between the S-SECEL and the EORTC and HAD questionnaires lent support
      to the construct validity of the S-SECEL and indicated that the questionnaire was
      sensitive to clinical change. The changes in S-SECEL correlated most strongly
      with changes in the EORTC QLQ-H&N35 speech scale, moderately with changes in the
      QLQ-C30 role and emotional functioning and global QoL scales, while the weakest
      correlations were with changes in physical functioning. The S-SECEL was sensitive
      to changes in communication dysfunction, with convergent and discriminant
      validity of longitudinal assessments, and with relevance for the quality of life
      of patients with laryngeal cancer receiving different treatment modalities.

PMID- 12195746
TI  - Management of hot flushes in breast cancer patients.
AB  - In breast cancer patients, menopausal symptoms such as hot flushes can be a
      bothersome problem, with a significant impact on quality of life. Hormone
      replacement therapy, the mainstay for treatment of these symptoms in healthy
      women, is traditionally contraindicated. There are, however, several other
      strategies for the management of flushes in breast cancer patients and these are
      reviewed in this article.

PMID- 12195747
TI  - A population-based study on the first forty-eight breast cancer patients
      receiving trastuzumab (Herceptin) on a named patient basis in Sweden.
AB  - Several studies have presented data on the efficacy and tolerability of
      trastuzumab within clinical trials. As a minority of patients is included in
      these trials, we undertook this retrospective study to describe trastuzumab
      therapy in clinical routine and its tolerability. We reviewed the medical records
      of the first 48 patients in Sweden who received treatment with trastuzumab on a
      named patient basis with (n = 29) and without (n = 19) chemotherapy. Forty-six
      patients had metastatic disease and had failed to respond to several prior
      regimens before starting antibody treatment. Two patients had locally advanced
      breast cancer failing on given neoadjuvant therapy. Patients with breast cancers
      with strong (3+) c-erbB-2 overexpression tended to have an improved survival from
      start of trastuzumab treatment versus those with a moderate (2+) overexpression
      (p = 0.09). Adverse events were registered in 22 patients (46%). The most common
      and acute side effects were fever and chills (7 patients, 15%). The toxicity
      seemed reasonable but two patients (4%) suffered serious cardiac events, both of
      them having received previous treatment with antracyclines.

PMID- 12195748
TI  - HER-2--a possible target for therapy of metastatic urinary bladder carcinoma.
AB  - Human epidermal growth factor receptor 2, HER-2, is overexpressed in various
      tumours, e.g. breast- and bladder tumours. The aim of this study was to predict
      the potential use of HER-2 receptors as targets in systemic treatment of
      disseminated bladder tumours. HER-2 expression was assessed in bladder carcinoma
      metastases and the corresponding primary tumours, and subsequently compared with
      the EGFR expression. HER-2 and EGFR expression was analysed by
      immunohistochemistry in formalin-fixed, paraffin-embedded tissues from 21
      patients with metastatic bladder carcinoma. HER-2 was overexpressed in 81% of the
      primary tumours and in 67% of the metastases. All HER-2-positive metastases were
      from HER-2-positive primary tumours. The results for EGFR were 71% of both
      primary and metastases-positive tumours. In 90% of the primary tumours and 86% of
      the metastases, at least one of the receptors was overexpressed. These results
      suggest that HER-2 targeted therapy can be considered as an alternative or a
      complement to other modalities in the treatment of metastatic urinary bladder
      carcinoma.

PMID- 12195749
TI  - Expression of matrix metalloproteinase-9 and bombesin/gastrin-releasing peptide
      in human prostate cancers and their lymph node metastases.
AB  - Neuroendocrine differentiation and subsequent excretion of neuropeptides have
      been demonstrated to be associated with progression of human prostate cancer.
      Among neuropeptides found to exist in the prostate, bombesin/gastrin-releasing
      peptide has been shown to upregulate matrix metalloproteinase-9 (MMP-9) in human
      prostate cancer cell lines. Expression levels of bombesin, MMP-9, and neuron
      specific enolase were examined by immunohistochemistry in 41 cases of clinically
      organ-confined prostate cancers including 9 with microscopic lymph node
      metastases. Twenty-seven (64%) of the 41 radical prostatectomy specimens were
      positive for both MMP-9 and bombesin. Expression of these molecules was observed
      in almost the same population of the cancer cells. The remaining 14 cases were
      negative for both MMP-9 and bombesin. High-grade tumors (Gleason sum > or = 7)
      were more likely to express MMP-9 and bombesin (21/24:88%) than low-grade tumors
      (Gleason sum > or = 6) (7/17:41%). In eight of the nine cases with pathological
      lymph node metastases, expression of MMP-9 and bombesin was also noted in
      metastatic sites. Neuron-specific enolase was positive in 16 cases (39%) and not
      always associated with the expression of bombesin. Expression of bombesin and
      expression of MMP-9 are common in human prostate cancers and may be related to an
      aggressive phenotype.

PMID- 12195750
TI  - 131I-labelled anti-CD22 MAb (LL2) in patients with B-cell lymphomas failing
      chemotherapy. Treatment outcome, haematological toxicity and bone marrow absorbed
      dose estimates.
AB  - The experience with radioimmunotherapy in B-cell lymphomas using the rapidly
      internalizing antibody, anti-CD22 (LL2), is limited. In this study we
      investigated the efficacy and toxicity of 131I-labelled-LL2 for
      radioimmunotherapy in patients with B-cell lymphomas that failed one or two
      cytostatic regimens. Eleven patients were treated with one or repeated cycles of
      131I-anti-CD22 antibody, 1330 MBq/m2 (36 mCi/m2). Six of the 11 treated patients
      demonstrated an objective response, three of them with complete remission. All
      follicular (3 patients) and transformed lymphomas (2 patients) responded compared
      to one of four diffuse large B-cell lymphomas. Two out of six responders
      exhibited event-free survival (EFS), which was comparable with or longer than the
      EFS following primary anthracycline-containing chemotherapy. Non-haematological
      toxicity was mild. Haematological toxicity was associated with pretreatment
      clinical characteristics but not with estimated absorbed bone marrow doses.
      Objective remission following treatment with 131I-anti-CD22 can be achieved in
      patients with various subtypes of B-cell lymphomas, failing standard
      chemotherapy. Follicular or transformed lymphomas seem particularly responsive.
      Haematological toxicity seems to be dependent on the functional status of the
      bone marrow before radioimmunotherapy.

PMID- 12195752
TI  - Suction blisters for the investigation of radiation reactions in human skin.

PMID- 12195751
TI  - Assessment of hypoxia in experimental mice tumours by [18F]fluoromisonidazole PET
      and pO2 electrode measurements. Influence of tumour volume and carbogen
      breathing.
AB  - The aim of this study was to compare a non-invasive 18F-fluoromisonidazole
      ([18F]FMISO) PET assessment of tumour hypoxia with invasive Eppendorf pO2
      measurements in 150-1,500 mm3 C3H mammary carcinomas transplanted on the back of
      CDF1 mice. The tumour-bearing mice breathed either carbogen gas (95% oxygen, 5%
      CO2) or normal air during both examinations. Additional autoradiography was
      performed in separate tumours treated similarly. The PET [18F]FMISO examination
      significantly discriminated between tumours of carbogen and air-breathing mice.
      For the pO2 measurements, there was a significantly lower percentage of
      measurements below 2.5 mmHg for carbogen-treated mice compared with air-breathing
      mice. However, no direct correlation between the methods was seen. A correlation
      was found between tumour volume and Eppendorf estimates of tumour hypoxia for the
      animals breathing normal air, but no correlation was found between the PET
      endpoint and tumour volume. This may be due to low pO2 measurements obtained in
      necrotic tissue. Autoradiography confirmed lower [18F]FMISO uptake in tumours of
      carbogen-breathing animals compared with air-breathing animals, and demonstrated
      the heterogeneity of the tracer uptake in small compared with larger tumours.

PMID- 12195753
TI  - Raltitrexed as monochemotherapy induces a statistically significant increase in
      platelet count.

PMID- 12195754
TI  - High-dose chemotherapy in small cell lung cancer.
AB  - Improvements in small cell lung cancer (SCLC) therapy with conventional doses of
      drugs with or without radiotherapy have been poor, and the 5-year survival is
      discouraging. Since SCLC is highly sensitive to radiotherapy and chemotherapy,
      some studies have tried to improve survival by increasing the dose of the drugs.
      Within conventional ranges, dose intensity can be increased with the support of
      hematopoietic growth factors (G/GM-CSF) and/or shortening treatment intervals
      (e.g. weekly regimens). However, dose intensity could be increased by only 20-30%
      and a survival advantage was not definitively obtained. Given its high
      chemosensitivity already two decades ago, SCLC was one of the first malignancies
      deemed suitable for maximizing dose and dose intensity with the support of
      autologous bone marrow transplantation (ABMT). On the whole, results were
      disappointing and the procedure was nearly abandoned. Nowadays, some interest is
      emerging again due to the improvements in supportive care such as the
      availability of hematopoietic growth factors and the peripheral blood progenitor
      cells (PBPC).

PMID- 12195755
TI  - Breast cancer and pregnancy.
AB  - The diagnosis of breast cancer during pregnancy is a rare event, but the young
      age of the patient together with the emotional impact for both the family and the
      doctors make therapeutic choices usually very difficult. Until recently, the
      occurrence of pregnancy associated breast cancer was thought to hold a grave
      prognosis and therapeutic abortion was very often advised in common practice. The
      hormonal environment with the increase in estrogens and progesterone was the main
      factor for the fear of tumor stimulation. The course of breast cancer, however,
      does not appear to be adversely affected by continuation of pregnancy. In the
      last years it was realized that potentially curative therapies can be
      administered even when pregnancy is continued. Of course in the medical
      literature there is no randomized clinical trial helping in taking decision in
      this setting; however, a significant experience already exists in some
      institutions and can guide management in these difficult cases. The aim of our
      review is to give an answer to questions usually coming from various specialists
      who collaborate with the oncologists in treating these patients and furthermore
      to try and find some basic guidelines which can be used in the information of the
      patients regarding previous experience in this field. The problem of a pregnancy
      after treatment for breast cancer is also analyzed, as this aspect is an emerging
      issue in clinical oncology. The decision should be evaluated for each single
      patient, taking into account the prognosis of the patient and her desire of
      pregnancy.

PMID- 12195756
TI  - Suicide and suicidal thoughts in cancer patients.
AB  - BACKGROUND: [corrected] Many factors increase vulnerability to suicide in cancer
      patients. Uncontrolled pain and other physical symptoms, psychological distress,
      and existential suffering are related to suicide in oncology. There is a strong
      consensus that physicians and nurses are not adequately trained to manage the
      potential suicide patient. This paper offers suggestions for the early
      recognition of cancer patients at risk of suicide, for the planning of crisis
      intervention and a physician-patient communication strategy. METHODS: A review of
      the literature about suicide in cancer patients was carried out by MEDLINE and
      PSYLIT and peer contacts. RESULTS: Through a review of the literature and their
      clinical experience, the authors outline a number of vulnerability factors of
      suicide with the intention to help health professionals to face the dilemma of
      suicide in cancer patients. Clinical vignettes reveal how a patient may reject
      his/her suicidal intention if adequate pharmacological and psychosocial supports
      are offered. Other case reports of patients refusing cancer therapy show that
      suicide is a complex phenomenon touching ethical, sociological, medical and
      psychiatric issues. CONCLUSIONS: Our findings support the hypothesis that
      improved patient-physician communication, to supply adequate psychological crisis
      intervention, respect for patient-centered care, familiarity with the tenets of
      palliative medicine alongside effective education in suicidology, and the routine
      use of teamwork may reduce the need of suicide in cancer patients and probably
      the need to hasten death.

PMID- 12195757
TI  - Paclitaxel and doxorubicin combination in the first-line treatment of metastatic
      breast cancer.
AB  - Anthracyclines and taxanes are currently the most effective drugs in the
      treatment of metastatic breast carcinoma. The aim of this study was to determine
      the efficacy and toxicity of paclitaxel and doxorubicin combination in the first
      line treatment of metastatic breast cancer. Forty-five women with metastatic
      breast cancer were recruited in the study. Median age was 49 years (range, 33
      70). Treatment protocol: doxorubicin (50 mg/m2/day, 30-min infusion) followed by
      paclitaxel (200 mg/m2/day, 3-hr infusion) every 3 weeks. Response rates included
      complete response in 13 (28.9%) patients and partial response in 19 (42.2%)
      patients, with an overall response rate of 71%. Five (11%) patients had stable
      disease and 8 (18%) patients had progressive disease. At a median follow-up of
      19.7 months, median time to progression for all patients was 19.9 months (95%
      confidence interval, 12.8 to 27 months). Median overall survival time was 28.4
      months. Grade 3-4 nausea/vomiting and hematological toxicities were observed in
      12 (26%) and 6 (13.3%) patients, respectively. Cardiac toxicity was observed in 2
      (4.4%) patients. In this trial, paclitaxel and doxorubicin combination was
      demonstrated to be a favorable and active regimen in the first-line treatment of
      metastatic breast cancer.

PMID- 12195758
TI  - Chemotherapy with cisplatin and 5-fluorouracil chronomodulated infusion in
      locally advanced or metastatic/recurrent carcinoma of the cervix.
AB  - AIMS AND BACKGROUND: The purpose of this study was to review our experience with
      the combination of circadian chronomodulated 5-fluorouracil infusion in
      association with cisplatin in patients with locally advanced or metastatic cancer
      of the cervix in order to assess the activity and tolerability of the
      combination. METHODS: Twenty patients with locally advanced disease and 21
      patients with metastatic or recurrent disease were treated from January 1995 to
      May 1999. 5-fluorouracil (600 mg/m2, days 1 to 5) was administered by a
      continuous circadian-shaped infusion employing an external programmable portable
      pump; cisplatinum (20 mg/m2) was infused days 1 through 5 i.v. over a 2-hr
      period. Response to treatment was evaluated after 3 and 6 cycles of therapy.
      Patients with locally advanced disease who achieved a clinical shrinkage of their
      tumor or were at least stable were submitted to surgery; pelvic radiotherapy was
      administered to patients with disease progression. RESULTS: Seven patients with
      locally advanced disease achieved a partial clinical response (overall response,
      35%; 95% CI, 15.4-59.2), and 12 of 20 patients were submitted to surgery. Median
      progression-free and overall survival were 17 months and 36 months, respectively.
      Objective responses were observed in 9 of 21 patients with metastatic/recurrent
      disease (7 partial plus 2 minor responses: overall response 43%; 95% CI, 21.8
      65.9). Median time to progression and overall survival were 5 and 17 months,
      respectively. CONCLUSIONS: Cisplatinum plus 5-fluorouracil chronomodulated
      infusion showed a moderate but definite activity and was well tolerated in both
      groups of patients. In consideration of clinical results comparable to more toxic
      and expensive regimens reported in the literature, the combination appears to be
      a reasonable option especially for women with metastatic/recurrent cervical
      carcinoma and a promising treatment in combination with definitive radiotherapy
      in patients with locally advanced disease.

PMID- 12195759
TI  - Abdominal and pelvic CT for detection and volume assessment of peritoneal
      sarcomatosis.
AB  - OBJECTIVE: Peritoneal sarcomatosis is a common finding in patients with recurrent
      abdominal or pelvic sarcoma. CT of the abdomen and pelvis is the standard
      radiological examination for evaluation of tumor volume and location in the
      peritoneal cavity; however data regarding the reliability of recurrent sarcoma
      detection has not been available. The purpose of this study was to evaluate the
      sensitivity of CT in detecting recurrent peritoneal sarcomatosis. METHODS:
      Abdominal and pelvic CT scans of 33 patients with abdominal or pelvic sarcoma
      recurrence were retrospectively reviewed. Subsequently all patients underwent
      surgery at which time complete exploration of the abdomen and pelvis was
      performed. Twenty-five CT parameters were evaluated and statistically analyzed
      using the findings at surgery as a standard. RESULTS: Among the anatomic sites,
      the lesser omentum and the Douglas pouch showed a sensitivity of 100%. In the
      nine abdominopelvic regions sensitivity was greater than 85% in the central
      region, the left lower quadrant and the pelvis. In all regions and sites, the
      pelvis and Douglas pouch showed the highest accuracy (91%). The volume of tumor
      present within an abdominopelvic region influenced the sensitivity. A sensitivity
      of 72.5% was recorded when tumor nodules were less than 0.5 cm in diameter. This
      increased to 90% when tumor diameter was greater than 5 cm. CONCLUSIONS:
      Abdominal and pelvic CT is a reliable test to evaluate recurrent sarcoma. The
      nodules in the pelvis were most accurately detected. Even small nodules of 0.5 cm
      were detected; the sensitivity increased as the nodules became greater than 5 cm.

PMID- 12195760
TI  - Suppression of unspecific enhancement on breast magnetic resonance imaging (MRI)
      by antiestrogen medication.
AB  - AIMS AND BACKGROUND: The value of breast MRI may be impaired by unspecific
      enhancement. This may leave patients with difficult-to-assess breast tissue with
      an uncertain diagnosis. We examined whether this unspecific enhancement (which is
      mostly due to proliferative or hyperplastic changes of benign breast tissue) may
      be suppressed by antiestrogen medication. METHODS: In a trial of treatment, 10
      peri- or postmenopausal patients who exhibited diffuse and/or focal enhancement
      on breast MRI before tamoxifen medication agreed to undergo a short-term
      tamoxifen treatment. MRI monitoring was performed 2, 4 and 8 weeks after onset of
      antiestrogen therapy (tamoxifen, 30 mg per day). RESULTS: Six patients showed a
      significant decrease of enhancement. Unchanged (n = 3) or increased (n = 1)
      enhancement was seen in 4 patients. One of the three patients with unchanged
      enhancement proved to have diffuse lobular carcinoma in situ. CONCLUSIONS: Part
      of the unspecific enhancement seen on breast MRI can probably be suppressed by
      short-term antiestrogen medication.

PMID- 12195761
TI  - Breast microcalcifications studied with 3D contrast-enhanced high-field magnetic
      resonance imaging: more accuracy in the diagnosis of breast cancer.
AB  - AIMS: To evaluate the reliability of magnetic resonance imaging (MRI) performed
      with three-dimensional (3D) sequences in mammographically detected breast
      microcalcifications. METHODS: During an 8-month period, a group of 28 patients
      with mammographically detected microcalcifications suspicious for malignancy
      underwent MRI. Their ages ranged from 33 to 65 years. Examinations were performed
      with a 1.5 Tesia MR unit and a 3D T1 weighted sequence. Images were interpreted
      on the basis of morphologic parameters and dynamic behavior in the uptake of
      contrast medium (Gd-DTPA). Histologic findings were considered as the gold
      reference. RESULTS: Histologic analysis revealed invasive carcinoma in 7
      patients, 3 of which were associated with foci of lobular carcinoma in situ.
      Intraductal carcinoma was diagnosed in 8 patients, 1 of which was associated with
      a tubular carcinoma. Benign lesions accounted for 13 patients. All the neoplastic
      conditions showed enhancement on MR images (sensitivity, 100%), whereas early and
      intense enhancement was noted in 5 of 13 benign lesions (specificity, 61%). The
      positive predictive value was 75% and negative predictive value, 100%.
      CONCLUSIONS: Although an overlap in the enhancement behavior of malignant and
      some benign lesions is clearly evident, a careful interpretation of MR images is
      helpful in detecting and mainly ruling out breast cancer combined with
      mammographically suspicious microcalcifications.

PMID- 12195762
TI  - Interobserver agreement of the dermoscopic diagnosis of 129 small melanocytic
      skin lesions.
AB  - AIM AND BACKGROUND: Dermoscopic diagnosis of pigmented skin lesions is based on
      the evaluation of dermoscopic criteria (classical pattern analysis) and on
      alternative diagnostic methods, such as the ABCD (A, asymmetry; B, border; C,
      color; D, differential structures) rule based on the total dermatoscopic score.
      The aim of the study was to investigate the interobserver agreement of standard
      dermoscopic criteria between two observers and the diagnostic validity of
      dermoscopic diagnosis by pattern analysis and by the ABCD rule. STUDY DESIGN: The
      study included a total of 129 small (< or = 5 mm) melanocytic skin lesions
      selected from all lesions observed in consecutive patients between April 1996 and
      September 1998. Before surgery, each lesion was photographed with a Dermaphot.
      Dermoscopic images were examined independently by two observers to evaluate the
      presence or absence of standard dermoscopic criteria and to establish the
      dermoscopic diagnosis by pattern analysis and by the ABCD rule. RESULTS:
      Interobserver agreement for dermoscopic criteria varied from moderately good to
      good, with the highest agreement for radial streaks (k = 0.96) and the lowest for
      pseudopods (k = 0.49). Interobserver agreement was moderately good in dermoscopic
      diagnosis by pattern analysis (k = 0.48) and by the total dermatoscopic score (k
      = 0.44). The sensitivity and specificity of dermoscopic diagnosis by pattern
      analysis were 40% and 99%, respectively, for both observers. As regards the total
      dermatoscopic score (a cutoff score of < or = 5.45 vs > 5.45), sensitivity ranged
      from 80% to 100% and specificity from 48% to 59%. CONCLUSIONS: The study showed
      that the pattern analyses as well as the ABCD rule give a poor discrimination
      between benign and malignant lesions and do not add relevant information for
      management decision in small melanocytic lesions. However, close follow-up
      examinations of small equivocal melanocytic lesions using digital equipment allow
      evaluation of their dermoscopic features during progression and whether their
      rather commonly found atypical dermoscopic features are lost during their natural
      course of growth.

PMID- 12195763
TI  - Amitriptyline in neuropathic cancer pain in patients on morphine therapy: a
      randomized placebo-controlled, double-blind crossover study.
AB  - AIMS AND BACKGROUND: Amitriptyline is the most common analgesic adjuvant used in
      cancer patients with neuropathic pain, even though no specific studies have
      demonstrated a benefit. A randomized placebo-controlled, double-blind crossover
      study was designed to evidence the effects of amitriptyline in patients with
      neuropathic cancer pain. METHODS: Sixteen advanced cancer patients with
      neuropathic pain on systemic morphine therapy, no longer receiving oncologic
      treatment, presenting moderate pain (about 4 or more, but less than 7, on a
      numerical scale of 0-10) in the last week, and given a stable morphine dose in
      the last 2 days were admitted to the study. During the first week of study,
      patients were administered 25 mg of amitriptyline or equivalent drops of placebo
      at night for 3 days and 50 mg for the following 4 days. Doses for patients aged
      more than 65 years were 15 mg (first 3 days) and 30 mg (3 days after). After a
      week, a crossover took place for the second week, with the other treatment at an
      inverse sequence. Opioid consumption, pain intensity, symptoms and adverse
      effects, mood, sleep, patient's preference, quality of life before starting the
      study, the first week after and the second week after were recorded. RESULTS: No
      significant benefits in analgesia were found in the global pain intensity of the
      previous week of treatment, the least pain intensity or the pain evaluated just
      after a week of treatment, at the moment of the visit, when amitriptyline was
      compared with placebo. A significant difference was evidenced for the worst pain
      (P < 0.035). No differences in opioid doses during the period of study were
      found. Drowsiness, confusion and dry mouth were significantly more intense with
      amitriptyline than with placebo (P < 0.036, 0.003, and 0.034, respectively).
      There were no substantial differences between the two treatments in Spitzer's
      quality of life score and for each item. No differences in patients' preference
      for the two treatment periods were found. The analgesic effects of amitriptyline
      were slight and associated with adverse effects. CONCLUSIONS: In light of the
      results obtained in the study, the extensive use of the drug for cancer pain
      should be questioned.

PMID- 12195764
TI  - Pain mechanisms involved and outcome in advanced cancer patients with possible
      indications for celiac plexus block and superior hypogastric plexus block.
AB  - AIMS AND BACKGROUND: There is controversy about the role of neurolytic
      sympathetic blocks in advanced cancer, when pain syndromes may assume other
      characteristics, with a possible involvement of structures other than visceral.
      The aim of the present study was to assess the pain characteristics and the
      analgesic response of a consecutive sample of home care patients with pancreatic
      and pelvic pain, which would have possible indications for a celiac plexus block
      and a superior hypogastric block, respectively. METHODS: From January 1999 to
      December 1999, 400 consecutive advanced cancer patients were surveyed for a
      prospective longitudinal survey. We considered only patients who had pancreatic
      cancer or pelvic cancer with pain. RESULTS: Thirty-six patients were surveyed: 22
      patients had pelvic cancers and 14 had pancreatic cancer. Patients with pelvic
      cancers showed a longer survival than those with pancreatic cancer (P = 0.019).
      Patients with pelvic cancers more frequently showed a neuropathic component
      associated with a visceral or somatic mechanism than patients with pain due to
      pancreatic cancer (P = 0.019). When the pain mechanism was taken into
      consideration, patients with pelvic cancers with a neuropathic component showed
      worse pain relief than patients with pain due to pancreatic cancer (P = 0.040).
      CONCLUSIONS: Sympathetic procedures for pain conditions due to pancreatic and
      pelvic cancers should be intended as adjuvant techniques to reduce the analgesic
      consumption, and not as a panacea, given that multiple pain mechanisms are often
      involved because progression of disease is able to change the underlying pain
      mechanisms. Pancreatic pain seems to maintain visceral characteristics amenable
      to sympathetic block more than pain due to pelvic cancer.

PMID- 12195765
TI  - High-grade cervical squamous intraepithelial lesion during pregnancy.
AB  - AIMS AND BACKGROUND: An increasing incidence of high-grade squamous
      intraepithelial lesion (HSIL) has been observed among young women. Consequently,
      an increased number of cases are being discovered during pregnancy. We analyzed
      the clinical and therapeutic management of HSIL during pregnancy. METHODS: A
      retrospective study was conducted from 1979 to 1998, and 58 registries of women
      with a cytological or histological diagnosis of HSIL during the pregnant
      puerperal period were reviewed. Information obtained from medical records
      included age, gestational age at diagnosis, parity, age of first intercourse,
      number of sexual partners before pregnancy, tobacco use, cytologic and
      colposcopic findings, route of delivery, postpartum follow-up, and treatment.
      This information was compared with a non-pregnant control group with HSIL.
      RESULTS: The average age of pregnant women with HSIL was 27.9 +/- 5.2 years. The
      cytologic or histologic diagnosis of HSIL was made in the first trimester in 12
      (20.7%) women and in the second trimester in 30 (51.7%) women. Average parity was
      2.8 +/- 2 deliveries. Age of first intercourse ranged from 13 to 29 years (16.1
      +/- 3.3). Thirty-two women (55.1%) had more than one sexual partner before
      pregnancy. Thirty-seven (63.8%) refereed tobacco use. According to the
      aforementioned aspects, no statistical difference was found in relation to
      control, except to cervical ectopia, which was more frequent in pregnant women
      (56.9% versus 42.6%). From the total of 58 pregnant women with cytologic or
      biopsy HSIL diagnosis, 53 had HSIL diagnosis made on cervical biopsy directed by
      colposcopy performed during the pregnancy; 44 (83%) of them were submitted to
      conservative management. HSIL was diagnosed by cervical biopsy in postpartum
      evaluation in 76% pregnant women with vaginal delivery and 78.6% women who
      underwent cesarean section. CONCLUSIONS: A conservative management of HSIL in
      pregnancy is proposed, with colposcopic evaluation during gestation and
      postpartum, regardless of route of delivery.

PMID- 12195766
TI  - Reactivation of pulmonary tuberculosis in malignancy.
AB  - AIMS AND BACKGROUND: Deterioration of immunity due to local or systemic effects
      of the tumor itself and/or administered chemotherapeutics or radiotherapy may
      play roles in the reactivation of tuberculosis, increasing the mortality in
      patients with various malignancies. In a country with a high prevalence of
      tuberculosis such as Turkey, most people have inactive tuberculous lesions and
      tuberculin test positivity. Therefore, a prospective study was carried out to
      investigate the frequency of tuberculosis reactivation in patients with a
      malignancy. METHODS: Seventy-three patients with a malignancy and undergoing
      diagnostic fiberoptic bronchoscopy were enrolled in the study during a 2-year
      period (1993-1995). Bronchoscopic biopsies and cytologic materials were obtained.
      Bronchoalveolar lavage fluids, bronchial washings, and pre- and postbronchoscopic
      sputum specimens were also evaluated for acid-fast bacilli. A diagnosis of
      tuberculosis was based on smear and/or culture positivity for acid-fast bacilli.
      RESULTS: The mean age of the patients was 56.2 +/- 13.6 years, with a male/female
      ratio of 69/4. The biopsy proven malignancies were as follows: primary lung
      carcinoma (n = 66, 90.4%), lymphoma (n = 5, 6.8%), metastatic breast
      adenocarcinoma (n = 1, 1.4%), and acute myelocytic leukemia (n = 1, 1.4%). Thirty
      one of all patients had findings compatible with tuberculosis on radiology. The
      sputa and bronchial washing specimens were smear negative in all patients. Acid
      fast bacilli were grown on culture in 6 patients (8%) (primary lung cancer, n =
      5; non-Hodgkin lymphoma, n = 1). Four of these 6 patients had positive radiology
      for tuberculosis. These subjects were treated with a three- or four-drug anti
      tuberculosis regimen. Two months later, smears remained acid-fast bacilli
      negative, or no bacilli were grown on culture. CONCLUSIONS: The possibility of
      coexisting tuberculosis should be kept in mind in patients with a malignancy,
      especially those with lung carcinoma in countries with a high prevalence of
      tuberculosis. Pulmonary infections encountered in such patients should raise the
      suspicion of tuberculosis reactivation, and in addition to direct microscopic
      evaluation, sputum specimens and materials obtained by fiberoptic bronchoscopy
      should be cultivated for tuberculosis. Three-four-drug anti-tuberculosis regimens
      should be given, especially in countries with high drug-resistance rates for
      eradicating tuberculosis.

PMID- 12195767
TI  - The coming water crisis.

PMID- 12195768
TI  - When is a rebate a kickback?

PMID- 12195769
TI  - Aging of AIDS. The silent risk group for HIV infection: senior citizens.

PMID- 12195770
TI  - Lifesaving scope.

PMID- 12195771
TI  - Death at Fort Bragg.

PMID- 12195772
TI  - Genes + abuse = trouble.

PMID- 12195773
TI  - Tests on trial. Jobs and reputation ride on unproven drug screens.

PMID- 12195774
TI  - Flu's worst season.

PMID- 12195776
TI  - The secret of feeling full.

PMID- 12195775
TI  - Young and bipolar.

PMID- 12195777
TI  - The wife beaters of Kibale.

PMID- 12195778
TI  - West Nile: prepare, don't panic.

PMID- 12195779
TI  - High-dose intravenous cyclophosphamide therapy in severe SLE.

PMID- 12195780
TI  - High-dose cyclophosphamide for severe systemic lupus erythematosus.
AB  - Cytotoxic therapy is a cornerstone for patients with severe systemic lupus
      erythematosus (SLE). High-dose cyclophosphamide, 200 mg/kg, can induce a complete
      remission without the need for stem cell rescue in patients with autoimmune
      illnesses. Here we report on our first four patients treated for severe SLE with
      this treatment approach. Patients received cyclophosphamide, 200 mg/kg, divided
      over 4 days. Starting day 10, patients received filgrastim, 5 micrograms/kg/day,
      until their absolute neutrophil count (ANC) rose to 10.0 x 10(9)/l for two
      consecutive days. Disease activity as evaluated by scores from the Systemic Lupus
      Activity Measure-2, the SLE Disease Activity Index and the Responder Index for
      Lupus Erythematosus were completed before and after high-dose therapy. Before
      high-dose cyclophosphamide, SLE disease duration ranged from 8 to 21 (mean 12.5)
      years. Their average disease activity measured by SLAM-2 and SLEDAI was 15.5
      (range 11-19) and 23.25 (range 20-26), respectively. At a median of 22 (range 12
      39) months of follow-up, mean disease activity measured by SLAM-2 and SLEDAI
      decreased to 6.25 and 7.75, respectively. All patients experienced febrile
      neutropenia. No long-term morbidities or mortalities were observed. High dose
      cyclophosphamide is a therapy capable of decreasing disease severity in poor
      prognosis SLE patients. Future study is warranted for both refractory patients as
      well as primary therapy for patients with moderate to severe disease
      presentations.

PMID- 12195781
TI  - Effect of mycophenolate mofetil on severity of nephritis and nitric oxide
      production in lupus-prone MRL/lpr mice.
AB  - Mycophenolate mofetil (MMF), an immunosuppressive drug commonly used in organ
      transplantation, is increasingly being used to treat autoimmune diseases
      including systemic lupus erythematosus (SLE). Excessive production of nitric
      oxide (NO) by inducible nitric oxide synthase (iNOS) has been implicated in the
      pathogenesis of lupus nephritis. We evaluated the effect of MMF on the severity
      of nephritis and the production of NO in lupus-prone MRL/lpr mice. Eight-week-old
      female MRL/lpr mice (n = 20) were treated with MMF (100 mg/kg/day) by oral gavage
      for 12 weeks. Control mice (n = 20) received vehicle on the same schedule. The
      mice were killed after 12 weeks of treatment. Treatment with MMF significantly
      decreased the amount of proteinuria, prolonged survival and reduced the
      histological severity of glomerulonephritis. Urinary nitrite/nitrate excretion in
      the MMF-treated mice was significantly reduced during the first 8 weeks of
      treatment. However, by the end of the 12 weeks' treatment period, there was no
      significant difference between vehicle and MMF-treated mice in terms of urinary
      nitrite/nitrate excretion, intra-renal production of NO, expression of iNOS
      protein and induction of iNOS mRNA. We conclude that MMF is effective in
      attenuating the severity of nephritis in MRL/lpr mice. The beneficial effects of
      MMF on lupus nephritis during the early phase of the disease might be partly
      attributed to the inhibition of NO production. The inhibitory effect of MMF on NO
      production diminishes as the disease progresses. MMF probably has additional, as
      yet undefined mode of actions to fully account for its beneficial effects on
      lupus nephritis.

PMID- 12195782
TI  - Gonadal function in adolescents and young women with juvenile systemic lupus
      erythematosus.
AB  - The authors analysed the gonadal function and age of menarche of 23 female
      adolescents and young women with SLE, and correlated these with clinical, SLEDAI
      and therapeutic parameters. The presence of one or more clinical and laboratory
      parameters defined normal gonadal function: normal menstrual cycles with or
      without dysmenorrhea; elevated cervical mucus length; normal levels of plasma
      FSH, LH, estradiol, progesterone, prolactin and testosterone; normal urinary
      hormonal cytology; serial pelvic ultrasound compatible with ovulatory pattern;
      and present or previous pregnancy. The mean age of menarche (13.5 +/- 1.4 years)
      was greater than that found among 2578 healthy Brazilian adolescents (12.5 +/-
      1.3 years; P = 0.0002). The delay in menarche correlated with an increase in the
      duration of the disease (P = 0.0085) and the cumulative dose of prednisone (P =
      0.0013) used until the appearance of the menarche. The mean phase length in SLE
      was 31.5 +/- 10.3. Sixteen female (70%) patients showed normal and seven (30%)
      abnormal gonadal function. Gonadal function was not correlated with parameters of
      SLE. These results suggest that the patients of this study reach adulthood with a
      high chance of fertility.

PMID- 12195783
TI  - Allergic disorders in systemic lupus erythematosus: prevalence and family
      history.
AB  - The relationship between allergic disorders (such as atopic dermatitis, asthma,
      allergic rhinitis and allergic conjunctivitis) and systemic lupus erythematosus
      (SLE) is still unclear and controversial. We investigated the prevalence of these
      allergic disorders in SLE patients and their families. A questionnaire about the
      history of allergy was completed by 52 SLE patients and by 52 matched (including
      race, age, sex and region) non-SLE controls. Our results indicated that there was
      a significantly lower incidence of these allergic diseases in SLE patients,
      especially those who had an allergic family histories, when compared with the
      controls. These findings may be related to the immunological similarities and
      differences between SLE and various allergic diseases.

PMID- 12195784
TI  - Hair dye treatment use and clinical course in patients with systemic lupus
      erythematosus and cutaneous lupus.
AB  - The etiological role of hair dye treatment (HDT), some of them such as permanent
      hair dyes containing aromatic amines, in the development of SLE has been
      previously ruled out. However, the possible influence of HDT use on the course
      and prognosis of lupus patients has been assessed only in one short-term study.
      Since HDT is very extensive among the population, the knowledge of this possible
      negative effect may be very important. Thus, the aim of this study was to assess
      the long-term influence of several HDTs on the course and clinical severity of
      patients with both systemic lupus erythematosus (SLE) and cutaneous lupus (CL).
      In this longitudinal case series study, 91 SLE patients and 22 CL patients were
      prospectively studied from October 1988 to May 2000. They were divided into three
      groups: (a) non-HDT users--patients who have never used HDT (n = 65); (b) P-HDT
      users--HDT permanent type users, alone or in combination with other types of HDT
      (n = 28); (c) non P-HDT--users of other treatments different from permanent
      tinting (bleach, lowlights, etc; n = 20). In each patient we determined: (1)
      number of flares/year in SLE patients and worsening of cutaneous lesions for CL;
      (2) Systemic Lupus International Collaborating Clinics/American College of
      Rheumatology (SLICC/ACR) damage index; (3) predominant damaged organs/systems
      according to the HDT use and type of HDT; and (4) subjective impression about the
      disease evolution in relation to HDT use. No significant differences were found
      with respect to flares/year and SLICC/ACR damage index between the study groups.
      Non-HDT group presented more renal involvement and serositis than both HDT-user
      groups. No patient related the HDT use to the worsening of his disease.
      Therefore, in this study no evidence of an association between the long-term use
      of several types of HDT and the clinical activity and course of SLE and CL was
      found.

PMID- 12195785
TI  - Increased T-lymphocyte apoptosis/necrosis and IL-10 producing cells in patients
      and their spouses in Icelandic systemic lupus erythematosus multicase families.
AB  - The objective of this study was to evaluate apoptosis and production of IL-10 in
      SLE patients, their spouses and first-degree relatives in Icelandic SLE multicase
      families. Previously, increased IL-10 production has been found in all three
      groups. As IL-10 has been found to induce apoptosis in SLE, the percentage of
      lymphocytes undergoing apoptosis was evaluated, as well as the possible
      correlation between apoptosis and IL-10 production. Apoptosis and IL-10
      production were studied in SLE patients (n = 12) from SLE multicase families and
      their spouses (n = 12) and a matched control group of healthy individuals (n =
      10). The proportion of T and B lymphocytes undergoing apoptosis at 0, 24, 48 and
      72 h was detected by flow cytometry using Annexin V and PI staining and the rate
      of apoptosis was calculated. IL-10 production was studied simultaneously by
      ELISpot analysis of freshly isolated peripheral blood mononuclear cells. In
      addition, T lymphocyte apoptosis at t = 0 was investigated in a group of non
      household first-degree relatives (n = 10) and controls (n = 10). Antinuclear and
      antilymphocyte antibodies were analysed in all the groups. The SLE patients as a
      group had a significantly increased percentage of T lymphocytes in apoptosis at 0
      and 48 h and a significantly higher number of IL-10 producing cells as compared
      with the healthy controls (P = 0.03, 0.02 and 0.03, respectively). The spouses
      also had significantly increased percentage of T lymphocytes in apoptosis (t = 0)
      and a significantly higher number of IL-10-producing cells when compared with
      healthy controls (P = 0.01 and 0.02, respectively). There were no significant
      differences between the patients and their spouses. For apoptosis of B
      lymphocytes no difference was found between the groups. The SLE patients as a
      group had the highest rate of apoptosis. No correlation between the degree and
      rate of apoptosis and the number of IL-10-producing cells was detected. The first
      degree relatives did not have increased percentage of T lymphocytes undergoing
      apoptosis at t = 0 compared with healthy controls. The SLE patients had higher
      titres of ANA compared with the other groups. No correlation was detected between
      the ANA titre and the percentage of lymphocytes undergoing apoptosis. There was
      no correlation between disease activity as measured by SLEDAI and apoptosis. In
      conclusion, our results suggest that environmental factors common to both SLE
      patients and their spouses are associated both with the increased apoptosis and
      increased spontaneous production of IL-10, thus providing support for the notion
      that both environmental and genetic factors influencing apoptosis are of
      importance for the development of SLE.

PMID- 12195786
TI  - Thrombotic thrombocytopenic purpura in systemic lupus erythematosus: disease
      activity and the use of cytotoxic drugs.
AB  - Thrombotic thrombocytopenic purpura (TTP) is a rare and occasionally fatal
      haematologic disorder that can coexist with systemic lupus erythematosus (SLE)
      and other autoimmune diseases. We identified all cases of TTP seen in our
      institution over a 3 year period using a computerized database. We found that SLE
      activity (measured by the SLE Disease Activity Index) and TTP activity ran a
      parallel course in three patients with coexistent SLE and TTP. TTP in these three
      patients, although refractory to plasmapheresis, responded to cytotoxic therapy.
      These observations further support an autoimmune contribution to the pathogenesis
      of some cases of TTP. A literature review revealed that mortality in SLE patients
      with more severe, refractory TTP treated with plasmapheresis and cytotoxics, may
      not be higher than in patients responding to plasmapheresis alone (who are likely
      to have milder disease). These data suggest that cytotoxics may have a role in
      treatment of patients with active SLE and TTP refractory to plasmapheresis.

PMID- 12195787
TI  - Aseptic meningo-encephalitis related to dexibuprofen use in a patient with
      systemic lupus erythematosus: a case report with MR findings.
AB  - We report of a 22-year-old woman with systemic lupus erythematosus (SLE) who was
      admitted to the intensive care unit (ICU) because of obtundation and a febrile
      illness. These symptoms had occurred after ingestion of 16 tablets of
      dexibuprofen. Cerebral magnetic resonance imaging (MRI) disclosed multiple
      hyperintense white matter abnormalities without gadolinium enhancement. No
      infectious origin or signs of a lupus flare were found. Our report is the first
      description of MR findings in dexibuprofen-induced aseptic meningitis, which here
      is actually a case of meningo-encephalitis. Patients suffering from SLE show
      increased susceptibility to non steroidal anti-inflammatory drug (NSAID)-induced
      aseptic meningitis/encephalitis, an important differential diagnosis to be
      considered at the work-up of altered mental status.

PMID- 12195788
TI  - The immune development in a child born to a cyclosporin A-treated woman with
      systemic lupus erythematosus/polymyositis.
AB  - The case of a woman affected by an overlap syndrome systemic lupus
      erythematosus/polymyositis (PM), who presented with active myositis at the start
      of the pregnancy, is reported. Therapy with cyclosporin, corticosteroids,
      hydroxychloroquine and high-dose intravenous immunoglobulin induced a progressive
      remission of clinical and laboratory signs of myositis. At 33 weeks of gestation,
      after a premature pre-term rupture of membrane, a male child was delivered.
      Although premature, and small for gestational age, he had a normal growth, and
      did not show any clinical sign suggestive of immune deficiency. Lymphocyte
      phenotypical and functional studies, as well as response to vaccination, were
      also normal.

PMID- 12195789
TI  - Systemic lupus erythematosus presented as non-inflammatory necrotizing
      vasculopathy-induced ischemic glomerulopathy and small vessels-related ischemic
      cardiomyopathy.
AB  - The clinical significance of lupus non-inflammatory necrotizing vasculopathy
      (NINV) is not well established. For example, since lupus renal NINV is usually
      reported to coexist with proliferative and active glomerulonephritis, it is
      difficult to demonstrate the role of NINV on renal pathophysiology. Here we
      report a 16-year-old SLE boy with renal NINV presenting as ischemic
      glomerulopathy and small vessels-related ischemic heart failure. The renal biopsy
      demonstrated mild proliferative glomerulonephritis and NINV initially, and one
      month later repeated renal biopsy showed NINV with ischemic glomerulopathy. These
      findings established that NINV, but not proliferative glomerulonephritis, was
      responsive for his acute renal failure (ARF). Another interesting question is
      about the pathophysiology of his myocardial dysfunction. This patient presented
      typical angina and congestive heart failure (CHF). Echocardiograms and
      ventriculography revealed dilatation of four chambers and low ejection fraction.
      Serial electrocardiograms demonstrated evolutionary ischemic changes. Coronary
      angiography revealed no abnormality of large vessels. These findings suggested
      small vascular lesions-induced myocardial ischemia was the underlying mechanism
      of dilated cardiomyopathy. As myocardial biopsy was not done in our case, we
      could only speculate, but not prove, that the NINV observed in renal biopsy may
      also involve in cardiac microvascular beds. Nevertheless, this interesting case
      emphasized the role of obliterative small vascular lesions in the pathophysiology
      of ARF and myocardial dysfunction. The patient was treated with high-dose
      corticosteroid, plasma infusion and hemodialysis. His cardiac function improved
      gradually, however the renal function did not recover.

PMID- 12195790
TI  - Occurrence of thrombotic thrombocytopenic purpura in a systemic lupus
      erythematosus patient with antiphospholipid antibodies in association with a
      decreased activity of von Willebrand factor-cleaving protease.

PMID- 12195791
TI  - Protein losing enteropathy in systemic lupus erythematosus: role of diet and
      octreotide.

PMID- 12195792
TI  - Pecking at other birds and at string enrichment devices by adult laying hens.
AB  - 1. Bunches of white string (polypropylene twine) are particularly attractive
      pecking stimuli for both chicks and adult laying hens. Furthermore, these devices
      can retain the birds' interest over lengthy periods. It has also been
      demonstrated that birds with trimmed feathers elicit feather pecking. The present
      study was designed to determine whether string devices would retain their
      attractiveness in the presence of a competing stimulus: a trimmed hen. 2. Lohmann
      Brown hens were reared in 20 groups of 5 in floor pens with perches from 17 weeks
      of age. They were exposed to one of two treatments when they were 23 weeks old.
      One hen was removed from every pen and the feathers on her rump were trimmed.
      Immediately before her return two string devices were suspended from a perch in
      treatment 1 whereas no devices were included in treatment 2. Pecking behaviours
      were immediately observed for 30 min; this procedure was repeated later that day.
      The devices remained in the pens used in treatment 1 and these birds were
      observed again for 15 min after 14 d. 3. The string devices were pecked earlier
      and more than either the trimmed or untrimmed hens. Furthermore, the devices were
      still being pecked 2 weeks after their introduction. 4. The virtual absence of
      severe feather pecking and of aggressive head pecks precluded test of our
      hypothesis that the devices would divert potentially injurious pecking away from
      other birds. However, the fact that the birds showed sustained interest in the
      devices, even in the presence of a competing stimulus, supports our proposal that
      string may represent a practicable and effective form of environmental
      enrichment.

PMID- 12195793
TI  - Influence of light-dark schedules and stocking density on behaviour, risk of leg
      problems and occurrence of chronic fear in broilers.
AB  - 1. The aims of this study were to determine (1) the effect of light-dark
      schedules on the walking ability, the risk of tibial dyschondroplasia (TD) as
      well as the duration of tonic immobility (TI) reactions in commercial broiler
      flocks and (2) the effect of a daily dark period and reduced density on the
      behaviour of broiler chickens. 2. Experiment 1. Group 1 had a 2 to 8 h daily dark
      period from 2 to 26 d of age (light-dark programme A) at a stocking density of
      28.4 chicks/m2. Group 2 had 8 h of darkness daily from 2 to 38 d of age (light
      dark programme B) at 24 chicks/m2. The control group had 24 h continuous light at
      28.4 chicks/m2. 3. Experiment 2. Behaviour was studied with and without a daily 8
      h dark period and at high (30 chicks/m2) and low (18 chicks/m2) stocking
      densities. 4. Programme B reduced the prevalence of impaired walking ability,
      corresponding to gait score > 2, when compared with controls. The effect on
      walking ability corresponding to gait score > 0 approached significance. 5. Both
      light-dark programmes reduced the occurrence of TD. Programme B (combined with
      reduced stocking density), however, had the greater effect. 6. Both light-dark
      programmes reduced the duration of TI, compared with controls (mean = 426 s)
      Programme B resulted in a larger reduction (alpha = -156.9 s) than programme A
      (alpha = -117.0). 7. The proportions of chicks drinking, eating, pecking,
      scratching, standing and performing vertical wing-shakes increased--both when the
      8 h dark period and the reduced stocking density were applied separately and in
      combination (experiment 2). 8. For all behaviours, except standing, the effect of
      the dark period was largest in broilers kept at the high stocking density (d 40).

PMID- 12195794
TI  - Reliability and validity of a modified gait scoring system and its use in
      assessing tibial dyschondroplasia in broilers.
AB  - 1. The gait scoring system for broilers developed by Kestin et al. (Veterinary
      Record, 131: 190-194, 1992) has been widely used to evaluate leg problems. The
      many factors and measures associated with this scale have empirically established
      its external (biological) validity. However, published test-retest (within
      observer) reliabilities are poor, and inter-observer reliabilities are unknown.
      We evaluated several modifications to this scale aimed at improving its
      objectivity and reliability. 2. Eighteen naive observers scored a standardised
      video of birds exhibiting varying degrees of lameness, either using Kestin et
      al.'s system, or our modified system. 3. Test-retest reliability (0.906) for
      Kestin et al.'s system was higher than previously reported. Inter-rater
      reliability was also good (0.892). The modified system offered significantly
      better test-retest (0.948) and inter-rater reliabilities (0.943), without
      incurring costs in terms of time taken or difficulty of use. The systems were
      consistent, assigning individual birds the same score on average. 4. It is
      concluded that the modified system offers the advantages of reduced error within
      and between studies. 5. In a second experiment, we used our modified scoring
      system to examine the relationship between tibial dyschondroplasia (TD) and gait
      score in 267 selected broilers. 6. Neither the presence nor severity of TD
      affected gait score, suggesting that, at least in this strain of broilers, other
      leg problems like slipped tendons or torsional deformities had more influence on
      gait impairment than did TD.

PMID- 12195795
TI  - Occupational exposure of poultry stockmen in current barn systems for egg
      production in the United Kingdom.
AB  - 1. The occupational exposure to inhalable dust and ammonia of 12 stockmen working
      in barn systems conforming to the UK Royal Society for the Prevention of Cruelty
      to Animals (RSPCA) Freedom Foods requirements was measured and compared with
      established limits for occupational exposure. The influence of the type of task
      upon the daily exposure was assessed and comparisons of daily exposure were made
      with that of battery cage system stockmen. 2. The mean inhalable dust exposures
      experienced by poultry stockmen working in barn systems was 10.8 mg/m3 (9.5
      mg/m3, time-weighted average), for a complete working day. This was greater (P <
      0.01) than the mean dust exposure measured in current cage systems of 4.8 mg/m3
      (4.4 mg/m3, time-weighted average). The individual values of dust exposure for 4
      of the 12 barn stockmen exceeded the occupational exposure standard (OES) of 10.0
      mg/m3 for inhalable dust, whereas that of all of the individual cage stockmen
      taking part in this study did not. 3. The mean ammonia exposure experienced by
      poultry stockmen working in barn systems was 14 ppm (11 ppm, time-weighted
      average), for a complete working day. This also was greater (P < 0.01) than the
      mean ammonia exposure measured in current cage systems of 8 ppm (7 ppm, time
      weighted average). None of the individual values of ammonia exposures for both
      barn and cage system stockmen taking part in this study exceeded the OESs of 25
      ppm, although the short-term limit of 35 ppm for 15 min was exceeded on a number
      of occasions. 4. Current methods for assessing the combined effects of dust and
      ammonia indicated that 8 of the 12 barn stockmen were at risk compared with 1 of
      the 8 cage system stockmen. 5. The average dust burden in daily common tasks such
      as maintenance and collecting floor eggs ranged from 5 to 15 mg/m3, while
      intermittent common tasks such as nest box checks and litter spreading ranged
      from 13 to 35 mg/m3. Tasks that had the highest exposure values included sweeping
      and partition removal, ranging from 63.3 to 70.7 mg/m3. 6. Designs of the typical
      barn systems investigated offer little scope for reducing airborne dust for
      common daily tasks. Personal respiratory protection while carrying out tasks that
      result in high dust concentrations in barns is advisable.

PMID- 12195796
TI  - Effect of pre-incubation storage conditions on hatchability, chick weight at
      hatch and hatching time in broiler breeders.
AB  - 1. Eggs were stored for two different times at varying temperatures. The effects
      on hatchability, chick weight at hatch and hatching time were examined in two
      broiler breeder lines from 33 to 58 weeks of age. 2. Short storage (1 to 3 d).
      Storage at 20 degrees C compared with 16.5 degrees C reduced hatchability of all
      eggs set. No effect was observed on hatchability of fertile eggs, hatching time
      or chick weight. 3. Long storage (9 to 11 d). Storage at 16.5 degrees C compared
      with 10 degrees C decreased both hatchability of fertile eggs and chick weight at
      hatch. Incidence of early embryonic death increased and incubation time decreased
      at 16.5 degrees C compared with 10 degrees C. 4. Chicks from morning eggs were
      heavier than those from afternoon eggs irrespective of storage conditions. 5.
      Hatchability (all eggs set and fertile eggs) and chick weight varied with hen age
      irrespective of storage conditions. During long storage, hatching time varied
      with hen age independently of breeder line, storage temperature or egg laying
      time. 6. Hatchability (all eggs set and fertile eggs) was higher in line A than
      in line B. Line B eggs hatched later and produced heavier chicks than line A eggs
      irrespective of storage time.

PMID- 12195797
TI  - Monthly model for genetic evaluation of laying hens. II. Random regression.
AB  - 1. We investigated the use of monthly production records for genetic evaluation
      of laying hens, derived from a test day model with random regression in dairy
      cattle and compared it with other models. 2. Records of 6450 hens, daughters of
      180 sires and 1335 dams, were analysed using a model with restricted maximum
      likelihood (REML): traits considered were monthly and cumulative egg production.
      Five models were studied: (1) random regression with covariates derived from the
      regression of Ali and Schaeffer (Canadian Journal of Animal Science, 67: 637-644,
      1987) (RRMAS), (2) random regression with covariates derived from quartic
      polynomial (RRMP4), (3) fixed regression with covariates derived from Ali and
      Schaeffer (FRM), (4) multiple trait (MTM) and (5) cumulative (CM). 3. The models
      were compared on the basis of Spearman rank correlations of individual breeding
      values and sire breeding values estimated from subsets of full-sib split data.
      The hens (about 10% per generation) which ranked highest on their estimated
      breeding values from different models were compared phenotypically with their
      full records. 4. The estimates of heritability resulting from RRMP4 were biased
      upward from the estimates obtained from MTM, so this model was discarded. The
      heritabilities for monthly productions from RRMAS and MTM showed a similar
      pattern. They were high for the 1st month of production, decreased to their
      lowest value at about month 5 of production and increased again to the end of
      lay. 5. Spearman rank correlations between animal breeding values estimated by
      monthly models (RRMAS, FRM and MTM) were high, between 0.91 and 0.98, whereas
      those between estimates of monthly models and CM were lower, from 0.85 to 0.87.
      The correlations estimated either from intermittent months of measurements (odd
      vs even months) or full records were generally high, from 0.93 to 0.99.
      Information from odd months of production could be sufficient for cost-efficient
      recording schemes. The RRMAS generally had the highest correlation of sire
      breeding values between subsets of full-sib records, followed by MTM, RM and CM.
      Monthly models selected hens with higher productivity than the cumulative model.
      6. In conclusion, genetic evaluation based on monthly production may be better
      than using cumulative production and RRMAS appeared to be the best among the
      models tested here.

PMID- 12195798
TI  - Hen-feathering mutation HF*H may act as a eumelanising factor and modify the
      expression of autosomal barring.
AB  - 1. An investigation was conducted amongst the progeny from a mating between a Hen
      feathered Silver Spangled Hamburgh bantam male and a normal feathered Silver
      Fayoumi bantam female into the genotype of the plumage pattern of the latter. 2.
      Both breeds possess the marbled chickdown phenotype which has been shown to
      depend upon homozygosity of three genes: the birchen allele E*R at the extension
      locus, the dark brown Columbian-like eumelanin restrictor gene DB*B and the
      plumage pattern arranging gene PG*P. Furthermore, the Spangled Hamburgh was known
      to possess genes for Hen-feathering HF*H and for the melanotic ML*M eumelanin
      extension. The Fayoumi had been hypothesised to contain Columbian eumelanin
      restrictor genes CO*C. 3. The absence of lace-tailed laced segregants similar to
      the Sebright, of genotype homozygous HF*H, ER*R, CO*C, DB*B--ML*M--PG*P
      contradicts the hypothesis that the genome of the Fayoumi includes CO*C. 4.
      Comparisons of both Hen-feathered and normal feathered versions of the feather
      patterns discussed in this work demonstrated that the Hen-feathered version is
      more heavily eumelanised.

PMID- 12195799
TI  - Influence of the microstructure on the shell strength of eggs laid by hens of
      different ages.
AB  - 1. The eggshell is a bioceramic material constructed of columnar calcite crystals
      preferentially oriented with their c-axis perpendicular to the shell surface. 2.
      The influence of microstructure (crystal size, shape and crystallographic
      orientation of crystal grains) on the mechanical properties of eggshells (shell
      strength) was investigated using eggs from hens of different ages. 3. There was a
      strong correlation between crystallographic texture and the strength of the
      eggshell in the case of eggs laid by young hens. The strength of eggshells
      increased as the preferential orientation of the crystals constituting the
      eggshell decreased. 4. By comparing two age populations, the effect of hen age on
      eggshell properties was evaluated. In general, eggshells from aged hens had a
      lower breaking strength (less than half that of those laid by young hens) and
      showed a greater variability in their structural properties such as thickness,
      grain morphology and crystallographic texture. 5. Texture analysis revealed that
      shells from eggs laid by aged hens have two preferred crystal orientations, after
      (001) and (104), compared with mainly one, after (001), in eggs laid by young
      hens. 6. These observed changes in eggshell properties could be due to changes in
      the organic matrix of the eggshell associated with ageing of the hens.

PMID- 12195800
TI  - Relationships between digestibilities of food components and characteristics of
      wheats (Triticum aestivum) introduced as the only cereal source in a broiler
      chicken diet.
AB  - 1. The aim of the experiment was to establish relationships between chemical or
      physical characteristics of wheats (Triticum aestivum) and digestibilities of
      food components in broiler chickens fed on wheat-based diets. Twenty-two wheat
      samples, each differing by their cultivar origin, were included at 550 g/kg in
      diets offered to male Ross broiler chicks. The other main ingredients were soya
      bean meal (340 g/kg) and rapeseed oil (68.5 g/kg). Diets were given as pellets.
      2. In vitro viscosities of wheats measured as potential applied viscosity (PAV)
      or real applied viscosity (RAV) varied between 1.91 and 6.03, or between 0.95 and
      3.81 ml/g (dry matter basis), respectively. Hardness of wheats varied between 17
      (soft) and 95 (very hard), and lipase activity of wheats varied from 1 to 13.6
      (relative scale). 3. PAV and RAV values were not significantly correlated with
      hardness. PAV and RAV values were correlated with (80:20) ethanol:water
      insoluble, water soluble arabinoxylans (r = 0.961, 0.932, respectively), with the
      amount of water retained by cell walls (r = 0.656, 0.492, respectively), and with
      lipase activity (r = 0.600, 0.532, respectively. 4. Hardness was correlated with
      ash (r = -0.484), nitrogen (r = 0.534), mean particle size of wheat flours (r =
      0.631), and specific energy of pelleting (r = -0.574). 5. Wheat diets were
      evaluated in two assays with 3-week-old chicks, with 11 diets per assay. In each
      assay, a balance experiment was carried out using the total collection method.
      Growth performance was also measured during the balance experiment. 6. In vitro
      viscosity parameters were negatively correlated with diet AMEn (P < 0.05), lipid
      digestibility (P < 0.05) and, to a lesser extent, protein digestibility (P <
      0.05). In vitro viscosity data were positively correlated with food:gain ratio (P
      < 0.05) and water loss parameters (P < 0.05), and were not significantly (P >
      0.05) correlated with starch digestibility. 7. Wheat hardness-related parameters
      were correlated (P < 0.01) with individual starch digestibility (hardness,
      proportion of coarse particles in wheat flour, specific energy of pelleting: r = 
      0.273, -0.305, 0.212, respectively). 8. Wheat lipase activity was negatively
      correlated with individual lipid (r = -0.179; P < 0.05) and starch (r = -0.225; P
      < 0.01) digestibilities and with individual diet AMEn (r = -0.266; P < 0.001).
      Individual diet AMEn values were correlated (r = 0.175) with the values
      calculated by the EU AMEn prediction equation (Fisher and McNab, 1987). Among the
      correlations observed between the individual measured AMEn:EU predicted AMEn
      ratio and wheat parameters (P < 0.05), the correlation obtained with wheat lipase
      was the highest (r = -0.195). The correlations with lipase could be explained in
      part by strong correlations between lipase and in vitro viscosity parameters.

PMID- 12195801
TI  - Effect of feeding whole cereals on performance, starch digestibility and duodenal
      particle size distribution in broiler chickens.
AB  - 1. An experiment was conducted to study the effects of whole wheat, oats and
      barley at different inclusion levels on performance, starch digestibility,
      duodenal particle size distribution, gizzard weight and pH of gizzard contents
      for broiler chickens. 2. Feed consumption and weight gain were significantly
      reduced when ground cereals were replaced by whole cereals (P < 0.05). However,
      feed conversion efficiency was not affected by inclusion of up to 440 g/kg of
      whole wheat, and up to 300 g/kg of whole oats and barley. 3. Duodenal particle
      size was measured by laser diffraction to below 1 micron in size. A remarkably
      large proportion of particles were below 100 microns, with as much as 50% of the
      particles in the duodenum being below 40 microns in size. Inclusion of moderate
      amounts of whole cereals reduced the duodenal mean particle size. Large
      inclusions of whole cereals decreased (P < 0.05) the proportion of particles up
      to 40 microns in size, and increased (P < 0.05) the proportion with size between
      100 and 300 microns. 4. Starch digestibility was improved (P < 0.05) by replacing
      ground wheat or barley with whole wheat or barley. 5. There was no consistent
      effect of cereal species or feed form on the pH value of the gizzard contents.

PMID- 12195802
TI  - Effects of sources of protein and enzyme supplementation on protein digestibility
      and chyme characteristics in broilers.
AB  - 1. The purpose of this study was to evaluate the effects of protein source and
      enzyme supplementation on protein digestibility and chyme characteristics in
      broilers. 2. One hundred and twenty growing (13 d old) and 60 finishing (34 d
      old) Arbor Acre strain commercial male broilers were selected and placed into
      individual metabolic cages. 3. The experiment was a 5 x 2 factorial arrangement
      with 5 different sources of protein: casein, fish meal, soybean meal (SBM), soy
      protein concentrate (SPC), maize gluten meal (MGM) and two levels of protease
      (bromelain), 0 and 65 CDU/kg diets. 4. The diets were iso-nitrogenous and semi
      purified, with Cr2O3 as an indicator for determination of ileal digestibility and
      chyme characteristics. 5. Apparent ileal protein digestibility (AIPD) in both
      growing and finishing chickens was highest on the casein diet, followed by fish
      meal, SBM, SPC and MGM. 6. Enzyme inclusion did not improve protein
      digestibility, but significantly decreased the digesta pH value in the gizzard
      and increased pH in the ileum in the 3-week-old broilers. 7. The digesta pH
      values in the gizzard and duodenum were significantly lower in the SBM and fish
      meal groups compared with the other protein groups. The molecular weight
      distribution pattern of the soluble protein in the chyme of the gastrointestinal
      (GI) segments showed a similar trend, regardless of the enzyme inclusion or the
      stage of growth. 8. The molecular weight profile of soluble protein changed
      dynamically in the casein fed broilers from the gizzard to ileum and the low
      molecular weight proteins, < 7 kDa, reached maximum levels at the ileum. The
      molecular weight profile of the soluble protein in the SBM and SPC changed
      between the jejunum and the ileum and in the intermediate molecular soluble
      protein weight (7 to 10 kDa) was significantly decreased. This indicated that the
      hydrolysis process began from the middle to the posterior end of the small
      intestine. 9. Similar profiles were also shown with fish meal protein. The
      pattern of distribution, however, did not show any prominent change in the GI
      segments of the MGM group. 10. The pepsin, trypsin and chymotrypsin protease
      activity in the gizzard and duodenum were highest in the casein group and lowest
      in the MGM group as compared with the other protein groups. 11. The rate change
      in the patterns of molecular weight distribution in soluble protein and the
      digestive enzyme activity provide indications of the partial digestibility of
      different protein sources. The exogenous enzyme, bromelain, did not show any
      beneficial effect on protein digestion.

PMID- 12195803
TI  - Role of dietary calcium and available phosphorus in the aetiology of tibial
      dyschondroplasia in growing turkeys.
AB  - 1. Large White male turkeys from a heavy commercial male-line were fed 16 diets
      containing 4 concentrations of calcium (6, 10, 14 and 18 g/kg) and available
      phosphorus (3, 5, 7 and 9 g/kg) in a 4 x 4 factorial experiment. There were three
      replicates (pens) of each treatment and the skeletal health, morphology and
      mineral status of 4 turkeys from each pen were assessed at 7, 10 and 13 weeks of
      age. 2. The prevalence of tibial dyschondroplasia increased after 7 weeks of age
      and was present in 50 and 71% of turkeys respectively at 10 and 13 weeks. The
      lesion was localised in the caudal aspect of the proximal tibiae. Dietary calcium
      and available phosphorus did not affect the prevalence of the lesion except in
      turkeys on the diet containing 6 g calcium/kg, where body weight and the
      incidence of tibial dyschondroplasia were low. 3. Histological investigation
      showed no evidence of rachitic changes. 4. Low dietary calcium was associated
      with lower tibial plateau angles at 10 and 13 weeks of age. Tibial torsion and
      the angle of rotation were not affected by dietary treatments or age. Tibial
      torsion and the angle of rotation were not affected by dietary treatments or age.
      5. Increasing dietary calcium increased tibial radiodensity, cortical density and
      the widths of the cortex and proximal tibiotarsus. Radiodensities increased to 10
      weeks and were significantly lower at 13 weeks of age. 6. Bone ash, calcium and
      phosphorus declined with age, particularly between 10 and 13 weeks, whereas bone
      calcium: phosphorus ratios were not affected by dietary treatment or age. 7.
      Dietary calcium was positively associated with blood calcium and calcium ion
      concentrations and was without effect on blood phosphorus. Available phosphorus
      was associated positively with increased blood phosphorus and lower calcium ion
      concentrations but had no effect on total calcium. Alkaline phosphatase activity
      was low at high concentrations of dietary calcium with low available phosphorus
      and there was higher activity on diets containing low calcium and high available
      phosphorus.

PMID- 12195804
TI  - Interactions between dietary crude protein and essential amino acid intake on
      performance in broilers.
AB  - 1. The effect of diets with increasing concentrations of crude protein at either
      fixed essential amino acid concentrations or at fixed essential amino
      acid:dietary crude protein ratios on performance was examined in 1- to 4-week-old
      male Cobb chicks. Increasing crude protein intakes at constant essential amino
      acid concentrations was carried out at two dietary energy contents. 2. Increasing
      crude protein resulted in a linear decrease in feed intake while weight gain and
      feed efficiency changed quadratically with a smaller positive effect at the
      highest crude protein intakes. Feed intake decreased and feed efficiency
      increased with higher dietary energy and interactions between protein and energy
      were significant. Abdominal fat content and the efficiency of protein retention
      decreased with increasing dietary protein intake. 3. Using constant essential
      amino acid:crude protein ratios at increasing crude protein intakes resulted in
      (Trial 3) feed intake, weight gain and feed efficiency all increasing before
      reaching a plateau. Abdominal fat decreased with protein intake and the
      efficiency of protein retention was quadratic, decreasing at the higher protein
      intakes. 4. Multiple regression analysis of the results of the three trials
      indicated that partition of energy intake into maintenance, fat-free tissue
      growth, fat and the energy required to transform protein intake in excess of
      retention explained more than 98% of variation. 5. It is proposed that broiler
      performance at the lower protein intakes was limited by either non-essential
      amino acid (Trials 1 and 2) or essential amino acid (Trial 3) intake whereas at
      high protein intakes the decreased efficiency of amino acid utilisation after
      growth requirements are fulfilled resulted in poorer performance.

PMID- 12195805
TI  - Progesterone and oestrogen receptor immunoreactivity in the vagina of the
      immature ostrich, Struthio camelus.
AB  - 1. The presence of sperm storage tubules in the cranial, middle and caudal
      regions of the vagina in the immature ostrich was studied. In addition,
      progesterone and oestrogen receptor immunoreactivity in these regions was
      investigated. 2. Sperm storage tubules were observed only in birds with active
      ovaries. Progesterone receptor immunoreactivity was more intense in birds with
      active ovaries, whilst immunostaining for the oestrogen receptor was absent in
      birds with both active and inactive ovaries. 3. These results suggest that
      steroid hormones produced by the active ovary mediate the activation of the
      progesterone receptor.

PMID- 12195806
TI  - Utilisation of a sperm quality analyser to evaluate sperm quantity and quality of
      turkey breeders.
AB  - 1. A relatively new instrument known as a Sperm Quality Analyzer (SQA) offers a
      rapid assessment of sperm quality and quantity by providing a sperm quality index
      (SQI). The SQA measures a combination of the intensity of sperm activity and
      motile concentration by determining the number and amplitude of sperm movements
      per second in a capillary tube as detected through light beam interference. 2.
      Because the SQA has not been tested for its potential use in turkeys, the
      objective was to determine if the SQA could accurately respond to changes in
      turkey sperm concentration, viability, and motility in semen collected from
      turkey breeders. 3. The effect of varying concentrations of sperm on SQI values
      was evaluated by diluting replicate pools of semen from 4 different aged turkey
      breeder flocks with saline. Results from all 4 flocks showed that semen dilutions
      greater than 20-fold resulted in a linear decline in SQI values. 4. Additional in
      vitro analysis evaluated the effects of turkey sperm viability on the SQI under
      conditions of constant sperm concentration. Incubated, live sperm was mixed in
      various proportions with thawed, dead sperm to determine changes in viability.
      Increased proportions of dead sperm caused a decline in the SQI. 5. To assess
      sperm motility, turkey semen was incubated under either aerobic (motile) or
      anaerobic (immotile) conditions. Varied amounts of immotile and motile sperm
      samples were mixed. A linear increase in the SQI was observed as per cent motile
      sperm increased. 6. These results indicate that the SQA can respond to
      differences in turkey sperm concentration, viability, and motility using in vitro
      analyses.

PMID- 12195807
TI  - Use of a sperm quality analyser on semen of turkey breeders to monitor storage
      time effects and age-related changes during a reproductive cycle.
AB  - 1. A relatively new instrument known as a Sperm Quality Analyzer (SQA) offers a
      rapid assessment of sperm quality and quantity by providing a sperm quality index
      (SQI). The SQA measures the intensity of sperm activity and motile concentration
      by determining the number and amplitude of sperm movements per second in a
      capillary tube as detected through light beam interference. 2. The objectives of
      the current study were to determine if the SQA could accurately reflect changes
      in semen quality that occur with prolonged storage of semen and to determine the
      variation and change in SQI values among individual breeding male turkeys during
      their semen production cycle. 3. The effect of storage time on SQI values was
      evaluated by diluting semen with extender and placing the semen on an oscillating
      shaker at 4 degrees C for 8 h. The SQI values and sperm viability, expressed as %
      dead sperm, were recorded hourly. The SQI readings declined linearly with
      increased storage time while % dead sperm increased linearly with increased semen
      storage. 4. Semen from 220 individual males was analysed monthly for 9 months.
      Semen diluted 50-fold with saline had lower SQI values during pre- and post-peak
      phases of production (months 1, 7, 8, and 9 as compared with months 2 to 6 of
      semen production). The highest SQI values occurred during months 2 to 6. The
      largest variation in SQI values occurred during months 1 (CV = 26%) and 9 (CV =
      31%) with a CV that averaged 16% for the remaining months. 5. Correlation
      analysis of SQI values for each bird averaged over 9 months with individual male
      SQIs for each month showed monthly correlation coefficients that ranged from 0.22
      to 0.63. 6. These results indicate that the SQA accurately assessed the decline
      in sperm quality that occurs with prolonged storage of turkey semen and reflected
      age-related changes in semen quality and quantity that occurred during a semen
      production cycle of turkey breeders. In addition, the semen quality rank of some
      turkey breeders in a population changed with age.

PMID- 12195808
TI  - The development of thermal resistance of the feather coat in broilers with
      different feathering genotypes and feeding regimes.
AB  - 1. This study compared the development of thermal resistance of the feather coat
      in broilers, with early or late feathering genes, and with or without the naked
      neck gene, allowed ad libitum or restricted feeding. 2. Male and female broilers
      of one of the 4 genotypes were reared to 6 weeks of age and allocated to one of
      the two feeding regimes. The thermal resistance of the back and crop region was
      measured at weekly intervals. A sample of birds were killed at the same ages and
      total feather weight, primary and secondary flight feather weight, liver weight
      and abdominal fat weight were measured. 3. All three main factors, sex, feeding
      and genotype, had significant effects on feather weight over time. The primary
      and secondary flight feathers were less affected by feed restriction than the
      feather coat as a whole. Birds with the naked neck gene showed a greater
      depression in growth rate than birds with a normal neck under conditions of
      restricted feeding. 4. The thermal resistance of the feathers on the back was
      greater in females, increased by early feather growth and decreased by restricted
      feeding. 5. Relative to metabolic body size, birds on restricted feeding had a
      greater feather weight and a smaller liver. There was a marked reduction in fat
      deposition, to almost negligible levels by 6 weeks of age. 6. Broilers given
      restricted feeding, in preparation for breeding, would benefit by a warmer
      environment, particularly those with feathering genotypes which confer a lower
      thermal resistance.

PMID- 12195809
TI  - Steroids: reactions and partial synthesis.
AB  - The article reviews the progress in the chemistry of the steroids that was
      published between January and December, 2000. The reactions and partial syntheses
      of estrogens, androgens, pregnanes, cholic acid derivatives, cholestanes and
      vitamin D analogues are covered. There are 169 references.

PMID- 12195810
TI  - The biosynthesis of adenosylcobalamin (vitamin B12).
AB  - Vitamin B12, or cobalamin, is one of the most structurally complex small
      molecules made in Nature. Major progress has been made over the past decade in
      understanding how this synthesis is accomplished. This review covers some of the
      most important findings that have been made and provides the reader with a
      complete description of the transformation of uroporphyrinogen III into
      adenosylcobalamin (AdoCbl). 183 references are cited.

PMID- 12195811
TI  - The chemistry and biology of the bryostatin antitumour macrolides.
AB  - This review summarises the main developments that have occurred in bryostatin
      chemistry over the period 1982 to 2001 and has 117 references.

PMID- 12195812
TI  - Muscarine, imidazole, oxazole, thiazole, Amaryllidaceae and Sceletium alkaloids.
AB  - A review with 136 references covers the literature from July 2000 to June 2001 on
      the isolation, bioactivities, and synthetic highlights of complex natural
      products including muscarine, imidazole, oxazole, thiazole, Amaryllidaceae and
      Sceletium alkaloids.

PMID- 12195813
TI  - Oxidizing species in the mechanism of cytochrome P450.
AB  - This review discusses the mechanisms of oxygen activation by cytochrome P450
      enzymes, the possible catalytic roles of the various iron--oxygen species formed
      in the catalytic cycle, and progress in understanding the mechanisms of
      hydrocarbon hydroxylation, heteroatom oxidation, and olefin epoxidation. The
      focus of the review is on recent results, but earlier work is discussed as
      appropriate. The literature through to February 2002 is surveyed, and 175
      referenced are cited.

PMID- 12195814
TI  - Triterpenoids.
AB  - This review covers the isolation and structure determination of triterpenoids
      including squalene derivatives, lanostanes, cycloartanes, dammaranes, euphanes,
      tirucallanes, tetranortriterpenoids, quassinoids, lupanes, oleananes,
      friedelanes, ursanes, hopanes, isomalabicanes and saponins. The literature from
      January to December 2000 is reviewed and 277 references are cited.

PMID- 12195815
TI  - RNA-acting antibiotics: in-vitro selection of RNA aptamers for the design of new
      bioactive molecules less susceptible to bacterial resistance.
AB  - During the last few years, antibiotic multiresistance has been increasing, not
      only in hospitals, but also, more worryingly, in general medicine. Different ways
      are being explored to bypass this problem. RNA-acting antibiotics such as
      aminosides (aminoglycosides) bind to bacterial RNA causing premature termination
      of proteins and mistranslation in bacteria. It is now possible to study the
      interactions of such antibiotics with their target by in-vitro selection of RNA
      molecules that recognize these antibiotics (RNA aptamers, SELEX method). The
      knowledge of the antibiotic-RNA interactions represents a promising way for the
      rational design of new bioactive compounds less susceptible to bacterial
      resistance.

PMID- 12195816
TI  - Excipient crystallinity and its protein-structure-stabilizing effect during
      freeze-drying.
AB  - The relationship between mannitol crystallization during freeze-drying and its
      effects on stabilizing protein structures was studied using lysozyme, bovine
      serum albumin, ovalbumin, beta-lactoglobulin and lactate dehydrogenase as model
      proteins. FT-IR analysis of the protein secondary structure indicated
      perturbation of both alpha-helix and beta-sheet regions in freeze-drying without
      cosolutes, whereas the proteins retained most of their native structure in co
      lyophilization with sucrose. Mannitol protected the protein structure to
      different degrees depending on the crystallinity. The combination of mannitol
      with potassium phosphate buffer reduced the mannitol crystallinity and the
      structural changes occurring during freeze-drying, whereas mannitol by itself
      showed little stabilizing effect. Heat-treatment of the frozen solutions at -10
      degrees C resulted in a higher mannitol crystallinity and a smaller stabilizing
      effect in freeze-drying. The secondary structure perturbation was mostly
      reversible in rehydrated solutions. The varied structure-stabilizing effects of
      mannitol paralleled its effects on maintaining lower concentrations of enzyme
      activity during freeze-drying. These results confirm the contribution of
      molecular interactions between amorphous excipients and proteins (e.g. hydrogen
      bonding) to structure stabilization during freeze-drying.

PMID- 12195817
TI  - Solvent change co-precipitation with hydroxypropyl methylcellulose phthalate to
      improve dissolution characteristics of a poorly water-soluble drug.
AB  - Research compound GWX belongs to biopharmaceutical classification system type II,
      and hence shows dissolution-rate-limited absorption. To improve its dissolution
      performance, GWX was formulated as a co-precipitate with hydroxypropyl
      methylcellulose phthalate (HPMCP). Co-precipitates with various drug-HPMCP ratios
      were prepared and characterised using modulated differential scanning calorimetry
      (MDSC), X-ray powder diffraction, HPLC and dissolution testing. Co-precipitates
      with 1:9 and 2:8 drug-HPMCP ratios showed the highest extent of dissolution after
      both 5 and 90 min, followed by 3:7, 4:6, and 5:5 drug-HPMCP co-precipitates, in
      respective order. Co-precipitates with drug-HPMCP ratios of 6:4 and greater
      showed no significant improvement in dissolution over crystalline drug alone. The
      amounts of crystalline and amorphous drug in co-precipitates, as determined by
      MDSC, and HPLC quantification of the total amount of drug in co-precipitates were
      used to determine the amount of drug incorporated into solid solution. It was
      found that dissolution rate and extent was correlated to the amount of drug
      incorporated into amorphous solid solution for the 1:9 to 5:5 drug-HPMCP ratio co
      precipitates. Amorphous drug alone and physical mixtures of drug and HPMCP showed
      very little and no significant improvement in dissolution rate or extent,
      respectively, above crystalline drug alone. Amorphous drug alone re-crystallized
      to a large extent within 1 min of contact with the dissolution medium, whereas
      4:6 drug-HPMCP co-precipitate showed a lower degree of re-crystallization and 2:8
      drug-HPMCP co-precipitate showed very little re-crystallization. It was concluded
      that the likely mechanisms of improved dissolution of low drug-HPMCP ratio co
      precipitates were improved wetting or increased surface area for mass transfer,
      thermodynamically enhanced dissolution of a higher energy amorphous form and
      inhibition of re-crystallization, when drug was incorporated into solid solution.

PMID- 12195818
TI  - Enhanced oral absorption of halofantrine enantiomers after encapsulation in a
      proliposomal formulation.
AB  - In this study, we evaluated the ability of a coated, encapsulated formulation to
      increase the oral bioavailability of (+/-)-halofantrine (HF) enantiomers, a drug
      with low and erratic oral bioavailability. After encapsulation of HF in
      distearoylphosphatidylcholine, the dried particles were coated with cellulose
      acetate phthalate. A suspension of the product was made using methylcellulose as
      a dispersion agent, and the product was administered to Sprague-Dawley rats to
      provide a HF dose of 7 mg kg-1 as the HCl salt. HF HCl powder in 1%
      methylcellulose with or without liposomal product excipients was also
      administered to separate groups of rats, which served as control groups. Serial
      blood samples were obtained from the rats and plasma was assayed by
      stereospecific high-performance liquid chromatography. There were no significant
      differences in the area under the concentration-time curve (AUC) or maximum
      concentration (Cmax) between the two control groups. Plasma concentrations of
      both HF enantiomers were significantly higher in the rats given HF as an
      encapsulated proliposomal formulation compared with the control groups. Compared
      with methylcellulose control, the encapsulation product resulted in increases of
      41 to 47% in the AUC of HF enantiomers, and 90 to 100% in Cmax. The ability of an
      encapsulated proliposomal product to significantly increase the oral absorption
      of HF was clearly demonstrated.

PMID- 12195820
TI  - Lung surfactant phospholipids inhibit the uptake of respirable microspheres by
      the alveolar macrophage NR8383.
AB  - Fluorescent poly(lactic-co-glycolic acid) microspheres of a respirable size were
      fabricated for use in a fluorescent activated cell sorting assay utilizing the
      continuous alveolar macrophage NR8383. This is a suitable model of alveolar
      phagocytosis, which permitted an investigation of the influence of phospholipid
      structure on the inhibition of phagocytosis of microspheres. Phospholipid
      inhibition was found to be independent of phosphatidylcholine alkyl chain length.
      Head group effects were investigated by studies employing phosphatidyl-choline, 
      serine, and -ethanolamine, and inhibition was shown to be independent of head
      group. Closer modelling of the lung environment by co-culturing NR8383 on A549
      alveolar epithelium showed type II secretions to also down-regulate phagocytosis.
      In addition, pre-incubation with microspheres coated with
      dipalmitoylphosphatidylcholine reduced the uptake of a second microsphere
      (fluorescein isothiocyanate-labelled latex).

PMID- 12195819
TI  - Contribution of P-glycoprotein to efflux of ramosetron, a 5-HT3 receptor
      antagonist, across the blood-brain barrier.
AB  - In-situ rat and mouse brain perfusion data indicated that the brain distribution
      of ramosetron (R-ramosetron), a 5-hydroxytryptamine3 (5-HT3) receptor antagonist,
      was extremely low compared with that expected from its lipophilicity. We
      hypothesized the involvement of an efflux system(s) and investigated the
      contribution of P-glycoprotein to efflux transport of ramosetron across the blood
      brain barrier by means of an in-vitro uptake study in cell lines that over
      express P-glycoprotein. We examined the contributions of mdr1a, mdr1b and MDR1 P
      glycoprotein by using LV500 cells, MBEC4 cells and LLC-GA5-COL300 cells, which
      over-express mdr1a P-glycoprotein, mdr1b P-glycoprotein and MDR1 P-glycoprotein,
      respectively. The uptake of [14C]ramosetron by LV500 cells and LLC-GA5-COL300
      cells was significantly lower than that by the respective parental cells. Next,
      we studied the effects of P-glycoprotein inhibitors, verapamil and ciclosporin,
      on uptake of [14C]ramosetron by these cell lines. The uptake of [14C]ramosetron
      by LV500 cells and LLC-GA5-COL300 cells was significantly increased in the
      presence of verapamil or ciclosporin, while verapamil did not affect the uptake
      of [14C]ramosetron by MBEC4 cells. These results indicate that the efflux of
      [14C]ramosetron is partly mediated by mdr1a P-glycoprotein, but not by mdr1b P
      glycoprotein, and that there is a difference in substrate specificity between
      mdr1a P-glycoprotein and mdr1b P-glycoprotein. Further, [14C]ramosetron was
      confirmed to be effluxed by human MDR1 P-glycoprotein. We conclude that the
      limited distribution of ramosetron to the brain is due, at least in part, to
      efflux mediated by the P-glycoprotein at the blood-brain barrier.

PMID- 12195821
TI  - Synthesis and evaluation of a monoreactive DOTA derivative for indium-111-based
      residualizing label to estimate protein pharmacokinetics.
AB  - The purpose of this study was to develop an indium-111 (111In)-based
      residualizing label for estimating the pharmacokinetics of proteins. 1,4,7,10
      Tetraazacyclododecane-N,N',N'',N'''-tetraacetic acid (DOTA), which produced a
      highly stable and hydrophilic 111In chelate, was selected as the chelating site,
      and the monoreactive DOTA derivative with a tetrafluorophenyl group as the
      protein binding site (mDOTA) was designed to avoid cross-linkings of proteins.
      mDOTA was synthesized with an overall yield of 11%. The stability in murine
      plasma, the radioactivity retention in the catabolic sites of proteins and the
      radiochemical yields of 111In-labelled proteins via mDOTA were investigated using
      human serum albumin (HSA), galactosyl-neoglycoalbumin (NGA) and cytochrome c (cyt
      c) as model proteins. 111In-labelled HSA via mDOTA was highly stable for 5 days
      after incubation in murine plasma. Long retention of radioactivity in the
      catabolic sites was observed after injection of 111In-DOTA-NGA in mice, due to
      the slow elimination of the radiometabolite from the lysosome. At a chelator
      concentration of 42.2 microM, 111In-DOTA-cyt c was produced with over 91%
      radiochemical yield. On the other hand, 111In-DOTA-lysine and 111In-DOTA were
      obtained with high radiochemical yields at lower chelator concentrations. These
      findings indicated that mDOTA would be an appropriate 111In-labelling agent for
      estimating protein pharmacokinetics. These findings also suggested that the
      introduction of a protein binding site at a position distal from the unmodified
      DOTA structure would be preferable to preparing 111In-DOTA-labelled proteins with
      higher specific activity.

PMID- 12195822
TI  - Effect of honey bee venom on proliferation of K1735M2 mouse melanoma cells in
      vitro and growth of murine B16 melanomas in-vivo.
AB  - Bee venom has been reported to exhibit antitumour activity in-vitro and in-vivo.
      Apoptosis, necrosis and lysis of tumour cells were suggested as possible
      mechanisms by which bee venom inhibited tumour growth. The aim of this study was
      to investigate potential mechanisms by which bee venom inhibits K1735M2 mouse
      melanoma cells in-vitro and B16 melanoma, a transplantable solid melanoma in
      C57BL/6 mice, in-vivo. The proliferation of K1735M2 cells in-vitro was inhibited
      by bee venom in a concentration- and time-dependent manner. The inhibition was
      indicated by the arrest of the cell cycle at the G1 stage, as detected by flow
      cytometric measurements. The bee venom induced apoptosis-like cell death as
      identified by histological observations and by DNA fragmentation. In the in-vivo
      experiments, the bee venom (1.0, 3.0, 9.0 mg kg-1 of body weight, on days 1-12)
      was injected intraperitoneally into mice 24 h after the mice were inoculated with
      B16 cells. Inhibition of the solid tumour was observed. Apoptosis of the K1735M2
      cells was suggested as the possible mechanism by which bee venom inhibited cell
      proliferation and induced K1735M2 cell differentiation in-vitro. The in-vivo
      experiment indicated that bee venom could be used as a chemotherapeutic agent
      against malignant tumours.

PMID- 12195823
TI  - Effect of a novel NSAID derivative with antioxidant moiety on oxidative damage
      caused by liver and cerebral ischaemia-reperfusion in rats.
AB  - Tissue ischaemia-reperfusion evokes toxic and harmful biochemical processes such
      as oxidative stress and inflammation. The aim of this study is to investigate the
      indices of tissue damage in rat liver and brain after ischaemia-reperfusion
      injury of these organs, and to study prospective cytoprotection of molecules such
      as the novel anti-inflammatory N-(2-thiolethyl)-2-(2-[N'-(2,6
      dichlorophenyl)amino] phenyl)acetamide (compound 1) and alpha-tocopherol. Two
      experimental models were studied: firstly, 30 min liver ischaemia via
      hepatoduodenal ligament clamping followed by 60 min reperfusion; and secondly, 45
      min cerebral ischaemia via bilateral common carotid artery occlusion followed by
      90 min reperfusion. Compound 1 and alpha-tocopherol were administered
      intraperitoneally before induction of ischaemia. We hereby report that compound
      1, a molecule that combines potent in-vitro antioxidant and in-vivo anti
      inflammatory activity with low gastrointestinal toxicity, offered protection in
      vivo against liver or brain ischaemia-reperfusion-induced damage. Both compound 1
      and alpha-tocopherol prevented changes in lipid peroxidation in the rat liver and
      brain tissue and in tumour necrosis factor (TNF-alpha) levels in brain. Also
      compound 1 attenuated glutathione depletion, evoked by ischaemia-reperfusion, in
      the rat brain but not in the liver. These results could be explained on the basis
      of the antioxidant/anti-inflammatory properties of compound 1 and suggest its
      beneficial effect and potential therapeutic use in post-ischaemic injury.

PMID- 12195824
TI  - Effects of BDF 9198 on left ventricular contractility in advanced spontaneously
      hypertensive rats with heart failure.
AB  - In the first part of this study, we characterized 24-month-old Wistar Kyoto (WKY)
      rats and spontaneously hypertensive rats (SHRs), their heart weights, and the
      responses of the isolated left ventricles to electrical stimulation. In the main
      part of the study, we tested whether the positive inotropic effects of BDF 9198,
      which prevents the closure of the cardiac sodium channel, were present in
      senescence and heart failure. Thus, we studied the effects of BDF 9198 on the
      left ventricle strips of 24-month-old WKy rats (senescence) and SHRs using
      contractility methods. In comparison with WKY rats, the left ventricles of 24
      month-old SHRs were hypertrophied and had prolonged times to peak contraction.
      BDF 9198 (10(-8) to 10(-6) M) was a positive inotrope on the left ventricles of
      WKY rats, with a maximum augmenting effect of 122% with BDF 9198 at 10(-7) M. The
      magnitude of the augmenting effects of BDF 9198 were reduced in SHR heart
      failure, with a maximum augmenting effect of 26% at 10(-7) M. BDF 9198 at 10(-6)
      M attenuated the responses of the SHR left ventricle to electrical stimulation.
      In conclusion, the potential of drugs that prevent closure of the sodium channel
      as positive inotropes in the treatment of heart failure should be further
      considered.

PMID- 12195825
TI  - Effect of hr-IL2 treatment on intestinal P-glycoprotein expression and activity
      in Caco-2 cells.
AB  - Caco-2 cells were used to investigate the effect of human recombinant interleukin
      2 (IL2) on intestinal P-glycoprotein (P-gp) transporter activity in-vitro. More
      specifically the efflux function of P-gp was studied by measuring the
      transepithelial transport of rhodamine-123, a fluorescent substrate of P-gp. Its
      transport was completely inhibited by two specific P-gp inhibitors, ciclosporin A
      and GG918, in our experiments. Conversely, these two specific P-gp inhibitors
      inhibited only 50% of transepithelial transport when [3H]vincristine was used as
      substrate. After Caco-2 cells were treated with 100 IU mL-1 (6.1 ng mL-1) IL2 for
      24 h, a significant diminution (21%) of P-gp transporter function was observed
      with rhodamine-123 substrate. This effect was also confirmed after 48 and 72 h of
      exposure to IL2. However, for higher concentrations of IL2 (1000 and 5000 IU mL
      1), diminution of P-gp function only occurred after a longer treatment period (48
      h and more). The inhibitory effect of IL2 on P-gp activity was found to be
      independent of tight junction function as demonstrated by constant
      transepithelial electrical resistance (TEER) measurements for all experimental
      conditions encountered in this study (time and concentration of IL2 exposure).
      Furthermore, the MDR1 mRNA level was found to be strongly repressed in Caco-2
      cells exposed with 1000 IU mL-1 IL2 for 72 h while the amount of MRP1 mRNA
      remained unchanged. In conclusion, acute incubation of Caco-2 cells with IL2
      induced a decrease of P-gp transporter expression and activity.

PMID- 12195826
TI  - Tachykinin-independent activity of capsaicin on in-vitro lamb detrusor.
AB  - The capsicum alkaloid capsaicin is an afferent fibre exciter. In the vesical
      bladder, capsaicin acts by releasing peptides stored in afferent fibres. The aim
      of this work was to verify the activity of capsaicin on in-vitro lamb urinary
      bladder and to ascertain whether this alkaloid evokes peptide release. Capsaicin
      relaxed about 80% of the lamb detrusor muscle preparations tested and contracted
      about 20%. Whereas neurokinin A and substance P antagonists, administered alone
      or together, left the contractile responses to capsaicin unchanged, atropine and
      tetrodotoxin totally inhibited contraction. Ruthenium red and indometacin
      abolished contractions and relaxation. The substance P and neurokinin A
      antagonists and the NO-synthesis inhibitor N omega-nitro-L-arginine methyl ester
      (L-NAME) left relaxation unchanged; conversely, the calcitonin gene-related
      peptide antagonist alpha h-CGRP (8-37) abolished this response. These results
      suggest that capsaicin relaxes lamb detrusor muscle not through tachykinins but
      by releasing CGRP from afferent fibres. Our observation that indometacin blocks
      the capsaicin response in in-vitro lamb urinary bladder also suggests a role of
      prostanoids.

PMID- 12195827
TI  - Causative agent of vascular pain among photodegradation products of dacarbazine.
AB  - The photodegradation products of the anticancer drug, dacarbazine, cause adverse
      reactions including local venous pain when injected intravenously. In this study,
      we attempted to identify which of these products is responsible. We synthesized
      or purchased five photodegradation products of dacarbazine (dimethylamine, 5
      diazoimidazole-4-carboxamide (Diazo-IC), 4-carbamoylimidazolium-5-olate, 5
      carbamoyl-2-(4-carbamoylimidazol-5-ylazo)imidazolium-5-olate and 2
      azahypoxanthine) and examined the pain reaction induced by their intraperitoneal
      administration in mice using an abdominal stretching or constriction assay. Only
      Diazo-IC clearly induced pain reaction in mice in a dose-dependent manner, the
      other products caused no pain reaction. The threshold concentration for pain
      reaction in mice was estimated to be about 0.1 mg mL-1. While diclofenac sodium
      significantly reduced acetic-acid-induced pain reaction in mice, it did not
      influence those induced by Diazo-IC. This result suggests that the mechanism of
      Diazo-IC-induced pain is different from that of acetic-acid-induced inflammatory
      pain. Dacarbazine itself produced marked relaxation of rat thoracic aorta strips
      in a concentration-dependent manner, but there was no difference between the
      activity of dacarbazine and its photo-exposed solution, so constriction or
      relaxation of blood vessels is unlikely to be a factor in the pain reaction. In
      conclusion, Diazo-IC generated by photodegradation of dacarbazine solution causes
      the side-effect of venous pain. Dacarbazine solution that has turned pink should
      not be used, because Diazo-IC is an intermediate in the formation of the reddish
      product, 5-carbamoyl-2-(4-carbamoylimidazol-5-ylazo)imidazolium-5-olate. Drip
      infusion preparations of dacarbazine should be shielded from light.

PMID- 12195828
TI  - AT-1015, a newly synthesized 5-HT2 receptor antagonist, dissociates slowly from
      the 5-HT2 receptor sites in rabbit cerebral cortex membrane.
AB  - The purpose of this study was to investigate the association and dissociation
      kinetics of [3H]AT-1015 from 5-HT2 receptors in rabbit cerebral cortex membranes
      using a radioligand binding assay method and to make a comparison with those of
      [3H]ketanserin binding. Scatchard analysis of [3H]AT-1015 binding in rabbit
      cerebral cortex membranes indicated the existence of a single class of binding
      sites (dissociation constant, Kd = 2.18 nM). The specific binding of [3H]AT-1015
      increased slowly with time and the association rate constant of [3H]AT-1015
      binding (k1 = 0.1229 min-1 nM-1) was two times slower than that of [3H]ketanserin
      binding (k1 = 0.2451 min-1 nM-1). The dissociation rate constant of [3H]AT-1015
      binding (t 1/2 = 37.03 min) was six times slower than that of [3H]ketanserin
      binding (t 1/2 = 6.29 min), when the addition of excess unlabelled ligands were
      AT-1015 and ketanserin, respectively. The dissociation rate constant of [3H]AT
      1015 was slowed to a greater degree (t 1/2 = 163.40 min and t 1/2 = 198.12 min)
      by the addition of ketanserin and sarpogrelate as excess unlabelled ligands than
      was that of [3H]ketanserin (t 1/2 = 17.76 min and t 1/2 = 18.45 min) by the
      addition of AT-1015 and sarpogrelate as an excess unlabelled ligand,
      respectively. These findings on the dissociation kinetics of [3H]AT-1015 have
      confirmed and supported previously reported evidence of the slower dissociation
      of AT-1015 from 5-HT2 receptors.

PMID- 12195829
TI  - Synthesis and properties of a naproxen polymeric prodrug.
AB  - A water-soluble polymeric prodrug containing a naproxen moiety was synthesized.
      The carboxylic groups of naproxen were condensed with the hydroxyl groups of 2
      hydroxyethyl methacrylate (HEMA) to produce a drug-linked monomer, denoted HN.
      The polymeric prodrug was prepared by copolymerization of HN with methacrylic
      acid. The molar percentage of HN in the polymeric prodrug was 26 mol%, as
      determined by 1H NMR. To investigate the pertinence of this polymeric prodrug,
      the hydrolysis was studied in-vitro with or without esterase or lipase. The
      kinetics of enzymatic catalysis was calculated from a Lineweaver-Burk plot. The
      anti-inflammatory activity was evaluated using the carrageenan-induced oedema
      test. The polymeric prodrug released a major fraction of the free naproxen and a
      significant fraction of the hydroxyethyl ester derived-naproxen. The maximum
      hydrolysis rate Vmax, and the Michaelis constant Km were calculated to be 2.16 x
      10(-5) equiv. mol L-1 min-1 and 5.11 x 10(-2) equiv. mol L-1. The maximum anti
      inflammatory inhibition of free naproxen appeared at 2 h and quickly decreased
      thereafter. In contrast, the polymeric prodrug showed a maximum at around 2-3 h
      and then slowly decreased. This indicates that the polymeric prodrug displays
      greater potency than free naproxen in the inhibition of acute inflammatory
      processes over long periods.

PMID- 12195830
TI  - Topical anti-inflammatory activity of extracts and compounds from Thymus
      broussonettii.
AB  - The topical anti-inflammatory activity of four extracts from Thymus broussonetii
      Boiss (Labiatae) leaves, a herbal drug used in Moroccan traditional medicine, has
      been studied using the croton oil ear test in mice. A bioassay-oriented
      fractionation revealed that the pharmacological activity is mainly in the
      chloroform extract. Fractionation and analysis of this extract allowed the
      identification of ursolic acid and oleanolic acid as the main anti-inflammatory
      principles. Some flavonoids (luteolin, eriodictyol, thymonin) and glycosides
      (luteolin-7-O-glucoside, luteolin-3'-O-glucuronide, eriodictyol-7-O-glucoside)
      were also isolated from the methanol extract.

PMID- 12195831
TI  - Discovery of novel inhibitors of inducible nitric oxide synthase.
AB  - We have discovered three compounds, 5-chloro-1,3-dihydro-2H-benzimidazol-2-one
      (FR038251), 1,3(2H,4H)-isoquinolinedione (FR038470) and 5-chloro-2,4(1H,3H)
      quinazolonedione (FR191863), which show inhibition of inducible nitric oxide
      synthase (iNOS). The iNOS inhibitory activity of the compounds was examined in
      comparison with that of aminoguanidine, a representative iNOS inhibitor.
      FR038251, FR038470 and FR191863 inhibited mouse iNOS, with IC50 values of 1.7,
      8.8 and 1.9 microM, respectively, in an in-vitro enzyme assay. These inhibitory
      activities are comparable with that of aminoguanidine (IC50 = 2.1 microM). The
      three compounds had iNOS selectivity 38- and 8-times, > 11- and 3-times, and 53-
      and 3-times compared with rat neuronal NOS and bovine endothelial NOS,
      respectively. These compounds concentration-dependently inhibited NO production
      in intact RAW264.7 mouse macrophages stimulated by lipopolysaccharide
      (LPS)/interferon-gamma. At 100 microM, FR038251, FR038470, FR191863 and
      aminoguanidine showed 81, 44, 54 and 78% inhibition of NO production,
      respectively. In an in-vivo experiment, FR038251, FR038470, FR191863 and
      aminoguanidine inhibited NO production in LPS-treated mice by 68, 40, 5 and 68%
      at an oral dose of 100 mg kg-1. The in-vivo inhibitory activity of FR038251 was
      almost identical to that of aminoguanidine. In conclusion, the three FR compounds
      are iNOS inhibitors with novel structures and may be candidate compounds leading
      to discovery of more iNOS inhibitors in the future.

PMID- 12195833
TI  - Polyamorphism: a pharmaceutical science perspective.

PMID- 12195832
TI  - Effect of the flavonoid galangin on urinary bladder rat contractility in-vitro.
AB  - Galangin is a flavanol with several biological activities. We have evaluated the
      effect of galangin on the contractile response elicited by electrical field
      stimulation (EFS) in the rat isolated urinary bladder. Galangin (10(-8)-10(-4) M)
      produced a concentration-dependent inhibition of the EFS contractile response
      without modifying the contractions produced by exogenous acetylcholine (10(-6)
      M). Blockade of adrenergic and cholinergic nerves with a combination of atropine
      (10(-6) M), phentolamine (10(-6) M) and propranolol (10(-6) M) or blockade of
      tachykinin NK1 and NK2 receptors with SR140333 (10(-7) M) and SR48968 (10(-6) M)
      did not modify the inhibitory effect of galangin. However, verapamil (10(-7) M)
      significantly reduced the inhibitory effect of galangin. It is concluded that the
      galangin inhibits EFS-induced contractions of the rat urinary bladder by acting
      on L-type calcium channels on presynaptic nerves.

PMID- 12195834
TI  - Serum proinflammatory cytokines and its relationship to clinical parameters in
      lung cancer patients with reactive thrombocytosis.
AB  - Proinflammatory cytokines Interleukin-1 beta (IL-1 beta) and Interleukin-6 (IL-6)
      play a significant role in the pathogenetic processes related to various
      malignant and inflammatory conditions. Leukocytosis, thrombocytosis and increased
      acute phase protein levels are part of a systemic inflammatory response. In this
      study, we measured the concentrations of IL-1 beta, IL-6 and ferritin as well as
      hemoglobin, lactate dehydrogenase (LDH), C-reactive protein (CRP) and erythrocyte
      sedimentation rate (ESR) in 23 patients (male 15, female 8, median age 68 years)
      with lung cancer and reactive thrombocytosis (LCRT), in 27 (male 18, female 9,
      median age 64 years) with benign inflammatory lung disorder (BILD) and 18 (male
      10, female 8, median age 62 years) lung cancer patients with a normal platelet
      count (LCNP). IL-1 beta levels were significantly higher in the three patient
      groups in comparison with control subjects (P < 0.001) but without significant
      difference among the three patient groups. IL-6 was higher in all three patients
      groups but only in the BILD group it was significantly higher than the control
      group (P < 0.05). However, no significant difference in IL-6 serum levels was
      found between the two lung cancer groups. CRP and LDH were significantly higher
      in the LCRT group in comparison with the other two patient groups (P < 0.01 and
      0.001, respectively), while ferritin was higher in both lung cancer groups in
      comparison with the BILD group (P < 0.001). Our data suggest that in lung cancer
      patients, reactive thrombocytosis is part of the systemic inflammatory reaction
      for which IL-1 beta and IL-6 may be intermediate but not independent mediators.

PMID- 12195835
TI  - Effects of formoterol (Oxis Turbuhaler) and ipratropium on exercise capacity in
      patients with COPD.
AB  - Although long-acting inhaled beta 2-agonists improve various outcome measures in
      COPD, no double-blind study has yet shown a significant effect of these drugs on
      exercise capacity. In a randomized, double-blind, placebo-controlled, crossover
      study, patients received formoterol (4, 5, 9, or 18 micrograms b.i.d. via
      Turbuhaler), ipratropium bromide (80 micrograms t.i.d. via pMDI with spacer), or
      placebo for 1 week. Main endpoint was time to exhaustion (TTE) in an incremental
      cycle ergometer test. Secondary endpoints were Borg dyspnoea score during
      exercise, lung function, and adverse events. Thirty-four patients with COPD were
      included, mean age 64.8 years, FEV1 55.6% predicted, reversibility 6.1%
      predicted. All doses of formoterol, and ipratropium significantly improved TTE,
      FEV1, FEF25-75%, FRC, IVC, RV and sGAW compared with placebo. A negative dose
      response relationship was observed with formoterol. Ipratropium increased time to
      exhaustion more compared with formoterol, 18 micrograms, but not with formoterol,
      4.5 and 9 micrograms. No changes in Borg score were found. There was no
      difference in the adverse event profile between treatments. In conclusion, 1 week
      of treatment with formoterol and ipratropium significantly improved exercise
      capacity and lung function compared with placebo. However, a negative dose
      response relation for formoterol was unexpected and needs further investigation.

PMID- 12195836
TI  - Applying evidence and theory to guide clinical decision making--implications for
      asthma management.
AB  - Evidence-based medicine has been described as the "conscientious, explicit and
      judicious use of current best evidence in making decisions about the healthcare
      of individual patients". Many sources of information may be used by doctors when
      making decisions about initiating asthma therapy. These include: personal
      experience, postgraduate education, continuous professional development and
      publications in peer-reviewed journals. However, despite these sources of
      information, available data suggest that it is often difficult to practice
      evidence-based medicine, particularly in general practice. In the future,
      physicians will be provided with better evidence of the relative efficacy of
      treatment to aid changes in clinical practice. This will be provided, in part, by
      large well-conducted clinical trials, systematic reviews and meta-analyses.
      Linked with these, will be other methods of presenting data, for example, the
      number of patients needed to treat (NNT) to prevent one clinically significant
      event (for example, an asthma exacerbation). Despite these advances,
      incorporation of evidence-based practice into routine asthma care will be a slow
      and complex process. However, this process can be facilitated by physician
      education and participation in intervention programmes. In addition, it is
      important that clinicians are trained in how to convey the best possible evidence
      to their asthma patients.

PMID- 12195837
TI  - Normocapnia during nIPPV in chronic hypercapnic COPD reduces subsequent
      spontaneous PaCO2.
AB  - Hypercapnia has been accepted during nasal intermittent positive pressure
      ventilation (nIPPV) and during subsequent spontaneous breathing in patients with
      chronic hypercapnic respiratory failure (HRF) due to COPD. We tested the
      hypothesis that nIPPV aimed at normalizing PaCO2 will reduce PaCO2 during
      subsequent spontaneous breathing. For that purpose 14 consecutive inpatients (age
      61.4 +/- 9.9 years) with chronic HRF due to COPD were established on passive
      pressure-controlled nIPPV in a stepwise approach. Assisted ventilation with
      supplemental oxygen to reach normoxemia was started followed by passive
      ventilation with a stepwise increment in the inspiratory pressure and finally by
      a stepwise increase in the respiratory rate to establish normocapnia. Baseline
      pulmonary function parameters were: FEV1 0.97 +/- 0.43 l, PaCO2 59.5 +/- 8.4
      mmHg, PaO2 49.9 +/- 7.8 mmHg, HCO3- 35.6 +/- 5.2 mmol/l, pH 7.39 +/- 0.04.
      Normoxemia as well as normocapnia was thus established by decreasing PaCO2 by
      19.5 +/- 7.0 mmHg during nIPPV within 8.8 +/- 3.8 days (P < 0.001) (inspiratory
      pressure 29.8 +/- 3.8 mmHg, respiratory rate 22.9 +/- 1.9 BPM). Spontaneous PaCO2
      measured 4 h after cessation of nIPPV decreased to 46.0 +/- 5.5 mmHg (P < 0.001),
      and HCO3- decreased to 27.2 +/- 3.0 mmol/l (P < 0.001). At 6 months of follow-up,
      II patients continued nIPPV with stable blood gases and with a decrease of
      P0.1/Plmax from 9.4 +/- 4.3% to 5.9 +/- 2.0% (P < 0.005). In conclusion,
      normalization of PaCO2 by passive nIPPV in patients with HRF due to COPD is
      possible and leads to a significant reduction of PaCO2 during subsequent
      spontaneous breathing and is associated with improved parameters of respiratory
      muscle function.

PMID- 12195838
TI  - The effects of pneumolysin and hydrogen peroxide, alone and in combination, on
      human ciliated epithelium in vitro.
AB  - We have investigated the effects of pneumolysin and H2O2, putative virulence
      factors of Streptococcus pneumoniae, on the ciliary beat frequency and structural
      integrity of human ciliated epithelium in vitro. Human ciliated epithelium was
      obtained by brushing the inferior nasal turbinate of healthy human volunteers.
      Ciliary slowing (CS) was measured using a photo-transistor technique and
      epithelial damage (ED) was documented using a visual scoring index. Effects of
      recombinant pneumolysin (100 ng/ml), a mutant pneumolysin preparation with
      markedly reduced haemolytic activity (100 ng/ml) and reagent H2O2 (100 microM)
      were measured alone and in combination, in the absence and presence of catalase
      (1000 units/ml). When used individually, both recombinant pneumolysin and H2O2
      caused significant (P < 0.05) CS and ED. The effects of H2O2 but not those of
      pneumolysin were almost completely attenuated by catalase, while the mutant
      pneumolysin preparation did not cause significant CS or ED. When used in
      combination, the effects of pneumolysin and H2O2 on CS and ED were additive as
      opposed to synergistic. These actions of pneumolysin and H2O2 may contribute to
      the pathogenesis of respiratory tract infections caused by the pneumococcus.

PMID- 12195839
TI  - Is there a cost-effective way to diagnose mild sleep-disordered breathing?
AB  - QUESTION OF THE STUDY: To determine the utility and the cost-effectiveness of
      oesophageal pressure, respiratory flow and movement, and oximetry (ORO) as a
      diagnostic tool for mild sleep-disordered breathing (SDB), as compared with
      overnight polysomnography (PSG). PATIENTS AND METHODS: Seventy-nine patients
      evaluated for mild SDB by PSG and simultaneously by oesophageal pressure (Pes)
      measurement, oximetry, respiratory flow and respiratory movement on a single
      night. An oesophageal event (OE) was defined as irregular respiration with
      crescendo in Pes and rapid return to baseline with a minimal increase in the
      negative Pes at the end of the OE of at least 5 cm H2O or more than 50% of the
      baseline level. SDB was defined by ORO when oesophageal events were > 5/h, and by
      PSG when the respiratory disturbance index was > 5/h. The diagnostic accuracy and
      cost-effectiveness of ORO were compared with PSG. RESULTS: Although the ability
      of ORO to detect SDB was poor: sensitivity 64%, specificity 78%, use of ORO for
      screening prior to PSG would have saved 5000 EUR per 100 patients compared to
      initial PSG. CONCLUSION: Using the combination of oesophageal pressure,
      respiratory flow and movement and oximetry for the diagnosis of mild SDB is not
      cost-effective, because of its poor diagnostic accuracy. New devices having
      alternative means to predict arousal and respiratory effort variation should be
      evaluated for cost-effectiveness.

PMID- 12195840
TI  - Tumor necrosis factor-alpha serum levels, weight loss and tissue oxygenation in
      chronic obstructive pulmonary disease.
AB  - Weight loss has been recognized as a feature of advanced emphysema and a factor
      of poor prognosis, but its mechanisms remain obscure. Studies have demonstrated
      high serum concentrations of TNF-a (cachexin) in chronic obstructive pulmonary
      disease (COPD) patients with emphysema. Pink puffers (PP) COPD patients have
      worse tissue oxygenation when compared with blue bloaters (BB) COPD patients.
      Consequently, PP patients would become cachectic, whereas BB patients with better
      tissue oxygenation would not. The aim of this study is to test the hypothesis
      that malnutrition in emphysema is a cytokine-mediated marker of chronic
      progressive tissue hypoxia. Thirty male COPD patients, without clinical or
      laboratory evidence of infection and severe air way obstruction (FEV1 < 1.5 l)
      were allocated: 16 as pink puffers (PP) and 14 as blue bloaters (BB). Lung
      function measurements included FEV1, FVC, RV, TLC, DLCO and arterial blood gases
      on room air. TNF-a serum levels were measured by immunoenzymic method (ELISA).
      Tissue oxygenation was assessed from oxygen delivery (DO2), PvO2 and oxygen
      extraction ratio (O2ER) obtained after right heart catheterization with Swan Ganz
      catheter. PP patients demonstrated lower DLCO and higher TLC, FRC and PaO2 from
      BB. We found that oxygen delivery was better in our BB than in PP patients (CI
      2.9 +/- 0.2 vs 2.5 +/- 0.4 l/min/m2--P < 0.01, DO2 16.1 +/- 2.1 vs 13.1 +/- 0.2
      ml/min/kg--P < 0.001) and the same was found for tissue oxygenation (PvO2 34.6 +/
      2.9 vs 31.2 +/- 3.8 mmHg--P < 0.01, O2ER 0.27 +/- 0.02 vs 0.34 +/- 0.06%--P <
      0.001). The TNF-a values were higher in PP (31.3 +/- 26 pg/ml vs 15.2 +/- 9.9
      pg/ml--P < 0.05) and their percent fat-free mass (%FFM) was 49.6 +/- 11.5 vs 42
      +/- 8%--P < 0.001. We found that COPD patients with lower DO2 had increased TNF-a
      levels; but the correlations between TNF-a serum levels and PvO2 or O2ER were not
      statistically significant. TNF-a levels were elevated in PP patients with tissue
      hypoxia and may be a factor contributing to the weight loss of these patients.

PMID- 12195842
TI  - Expression of bronchodilator response: comparison of four indices.
AB  - Several indices have been suggested to express the bronchodilator response but
      there is no agreement on what is the ideal expression. The forced expiratory
      volume in I s (FEV1) was measured in 190 patients of bronchial asthma before and
      after inhalation of 200 micrograms salbutamol. Four different indices of
      bronchodilator response were calculated. The change in FEV1 was expressed as
      absolute value (delta FEV1), as a percentage of initial FEV1 (delta FEV1%
      initial), as a percentage of the predicted normal value (delta FEV1% predicted)
      and as a percentage of maximum achievable reversibility, i.e. the difference
      between predicted and initial values (delta FEV1% [predicted-initial]). A
      significant negative correlation was observed between delta FEV1 initial and
      initial FEV1% predicted (r = -0.33, P < 0.0001) but not delta FEV1 and initial
      FEV1% predicted, or between delta FEV1% predicted and initial FEV1% predicted.
      The values of delta FEV1% [predicted-initial] tended to reach towards infinity as
      the initial FEV1% predicted approached 100%. delta FEV1% predicted had similar
      sensitivity but greater specificity than delta FEV1% initial in detecting a true
      bronchodilator response. It was concluded that being dependent on the initial
      value, delta FEV1% initial was not an appropriate method to express the
      bronchodilator response. Although all other methods had limitations, delta FEV1
      and delta FEV1% predicted appeared to be better indices.

PMID- 12195841
TI  - Comparison of two budesonide powder inhalers, Easyhaler and Turbuhaler, in
      steroid-naive asthmatic patients.
AB  - The objective of this multicenter study was to compare the clinical efficacy,
      safety, and acceptability of Easyhaler and Turbuhaler for the delivery of
      budesonide 200 micrograms/dose twice daily in steroid-naive asthmatic patients.
      Three hundred and twenty-six newly diagnosed, steroid-naive adult patients with
      mild-to-moderate asthma were recruited into this randomized, double-blind, double
      dummy, parallel-group study, comprising a 2-week run-in period and 8 weeks of
      treatment. Patients received budesonide inhalation powder 400 micrograms/day
      either via Easyhaler (n = 159) or via Turbuhaler (n = 167), plus salbutamol
      inhalation powder (100 micrograms/dose) via Easyhaler as rescue therapy. The
      study was completed by 292 patients: 143 in the Easyhaler group and 149 in the
      Turbuhaler group. The primary outcome variable, mean morning peak expiratory flow
      (PEF), improved significantly and almost similarly by 36.3 and 30.6 l/min,
      respectively, from run-in to weeks 7-8. At weeks 7-8, the mean (SE) difference in
      morning PEF between the two treatments was 7.1 (9.4) l/min (90% CI from -8.4 to
      22.6) on per protocol analysis, which was within the defined limits for
      therapeutic equivalence. There were no significant differences between treatments
      in terms of secondary efficacy variables or adverse events. However, patients
      found Easyhaler more acceptable than Turbuhaler. The results show that budesonide
      via Easyhaler is clinically as effective as Pulmicort Turbuhaler when equal daily
      doses of budesonide are delivered to steroid-naive asthmatic patients. Moreover,
      patients found Easyhaler more acceptable than Turbuhaler, and a majority would
      prefer Easyhaler if given a choice.

PMID- 12195843
TI  - Few smokers develop COPD. Why?
AB  - COPD is a common disease and its major risk factor, cigarette smoking, has been
      identified. However, only a minority of smokers develop clinically relevant
      disease. Although, the current understanding of the pathogenesis includes an
      "abnormal inflammation" as a response to various noxious agents, its various
      pathways are not clear. Oxidative stress, inflammation, tissue damage and tissue
      repair (remodeling) are parts of the complex procedure leading to COPD. This is a
      review of the available literature concerning the "susceptible" smoker. An
      epidemiological model is discussed, putting emphasis on the timing of the
      exposure to cigarette smoke. There are evidences that respiratory adenoviral
      infection in early life could be also an important factor. Differences in
      nutrition could also play a role in protecting against the oxidative stress.
      Airway hyperresponsiveness failed to clarify the whole picture and is still open
      for debate. Genetic differences are the most likely explanations to describe the
      "susceptible" smoker. However, the only well-established genetic risk factor is
      the alpha-l-antitrypsin. Other candidate genes were reviewed, alpha-l
      antichymotrypsin, blood group antigens, vitamin-D binding protein, a2
      macroglobulin, immunoglobulin deficiency, extracellular superoxide dismutase,
      secretory leukocyte proteinase inhibitor, cathepsin G, tumor necrosis factor-a
      gene and others. Microsatellite DNA instability in COPD could be a useful tool to
      identify the locus of genetic alterations leading to COPD. Thus, in addition to
      exposure to exogenous factors, host factors, most likely several genes, are
      involved and affect various pathways of the pathogenesis of COPD.

PMID- 12195845
TI  - The diagnostic value of adenosine deaminase activity in sputum in pulmonary
      tuberculosis.
AB  - This study was carried out in Ataturk Chest Diseases and Surgery Center. It's aim
      to determine and compare sputum adenosine deaminase (ADA) activity in pulmonary
      tuberculosis (tb), lung cancer and chronic obstructive pulmonary disease (COPD)
      patients in order to assess its diagnostic value. PATIENTS AND METHOD: Eighty
      four patients (25 tb, 30 lung cancer and 29 COPD) were included in the study. ADA
      activity in sputum and serum was measured. Sputum ADA activities of tb patients
      were significantly higher than the other two groups (P < 0.05). Sputum/serum ADA
      ratios were similar in all groups. Sputum ADA activities between 150 and 200 U/L
      were the measurements with the best test performance according to the ROC curve.
      Sensitivity, specificity, positive predictive value, and negative predictive
      value were 44.0, 86.4, 57.8, 78.4% for 150 U/L and 32.0, 96.6, 80.0, 77.0% for
      200 U/L, respectively. Area under the curve was 0.663. Because of low
      sensitivity, routine determination of ADA activity in sputum for the diagnosis of
      pulmonary tb is not recommended. However, it can be helpful in the diagnosis of
      smear-negative cases who are strongly suspected of tb.

PMID- 12195844
TI  - HPA-axis effects of nebulised fluticasone propionate compared with oral
      prednisolone in childhood asthma.
AB  - The aim of this study was to compare the effect of 7 days nebulised fluticasone
      propionate (FP) with oral prednisolone on 24-h urinary-free cortisol excretion,
      systemic exposure and safety. This was a randomised, double-blind, double-dummy,
      two-way crossover study. Thirty-one children (19 male, 12 female, mean age 8
      years) with stable asthma were randomly assigned to 7 days treatment with either
      FP Nebules (2 x 0.5 mg/2 ml bd) or prednisolone tablets once daily (2 mg/kg/day
      for 4 days [maximum 40 mg] followed by 1 mg/kg/day or half the original dose for
      3 days [maximum 20 mg]). After a 2-4 week washout period, patients received the
      second treatment for 7 days, followed by a 2-week follow-up visit. The primary
      outcome measure was 24-h urinary-free cortisol concentrations corrected for
      creatinine. Nebulised FP (1 mg bd) had significantly less effect on 24-h urinary
      free cortisol excretion than oral prednisolone (8.9 ng/ml for FP and 5.0 ng/ml
      for prednisolone, P = 0.001). Systemic exposure to FP was also low. In
      conclusion, FP Nebules had significantly less effect on hypothalamic-pituitary
      adrenal axis function than oral prednisolone in asthmatic children when used at
      doses recommended for the treatment of an acute exacerbation of asthma.

PMID- 12195846
TI  - Rhinitis increase the risk for adult-onset asthma--a Swedish population-based
      case-control study (MAP-study).
AB  - The aim of the study was to examine certain predictors, especially non-infectious
      rhinitis, and the risk for adult-onset asthma. A nested case-control study of
      adult-onset asthma was performed in a random sample from the general population
      (n = 15,813), aged 21 to 51 years. Cases for the study included subjects
      reporting physician-diagnosed asthma (n = 235) and controls (n = 2044) were
      randomly selected from the whole population sample. The case-control sample was
      investigated with a comprehensive respiratory questionnaire. Odds ratios were
      calculated stratified for sex, year of diagnosis and birth-year. Adult-onset
      physician-diagnosed asthma was associated with occurrence of non-infectious
      rhinitis before asthma onset (OR = 5.4, 95% CI 4.0-7.2), especially among smoking
      non-atopics (OR = 9.1, 95% CI 5.3-15.4). Smoking before asthma onset increased
      the risk for asthma (OR = 1.5, 95% CI 1.1-2.1). In conclusion, this population
      based case-control study indicate that non-infectious rhinitis and current
      smoking, especially among non-atopics, are associated with increased risk for
      adult-onset asthma.

PMID- 12195847
TI  - High prevalence of obesity in asthmatic patients on sick leave.
AB  - Obesity and asthma are common chronic diseases in the industrialised world. The
      aim of the present study was to investigate a possible relationship between
      asthma and obesity among persons on sick leave due to respiratory disorder. The
      diagnosis of asthma (n = 237) was made in a three-stage model (questionnaire,
      telephone interview and clinical examination) in persons on sick leave due to any
      respiratory disorder. Persons on sick leave due to non-specific spinal pain, (n =
      1231) and a general population sample (n = 5092) were used as references. Obesity
      (body mass index > 30 kg/m2) was found in 20.7% of the asthmatic patients on sick
      leave compared with 13.7% in the non-specific pain patients on sick leave and in
      6.5% of the controls (P < 0.001). It is not clear whether the increased
      prevalence of obesity among asthmatics reflects a true increase in asthma in
      obese persons or whether asthma-like symptoms occur because of obesity. Weight
      reduction schemes and weight maintenance programmes should be important
      components in treatment and rehabilitation plans for persons with asthma.

PMID- 12195848
TI  - The evolving clinical consultation.

PMID- 12195850
TI  - Hospitalists and consultant physicians in acute medicine.

PMID- 12195849
TI  - The changing face of acute medicine.

PMID- 12195851
TI  - Expanding nurses' roles: from vision to reality.

PMID- 12195852
TI  - The emerging role of clinical audit.

PMID- 12195853
TI  - Management of gastro-oesophageal varices.

PMID- 12195854
TI  - Assessment and management of chronic hepatitis C infection.

PMID- 12195855
TI  - Assessment and management of chronic hepatitis B.

PMID- 12195856
TI  - Investigation and treatment of ascites.

PMID- 12195857
TI  - Indication and assessment for liver transplantation.

PMID- 12195858
TI  - The relationship between physicians and the biomedical industries: advice from
      the Royal College of Physicians.
AB  - The relationship between a physician and a biomedical firm is often important,
      and can be useful to both parties. However, there is a danger that the
      substantial resources available to a biomedical firm might sometimes be used to
      interfere with a physician's independent professional judgment. For the
      reputation and good conduct of the profession and the industry, and for the
      welfare of patients, it is essential that this does not happen. Total absence of
      communication would prejudice the undoubted good which collaboration can achieve.
      This paper sets out what the Royal College of Physicians currently believes are
      appropriate boundaries: to the acceptance of gifts; to sponsorships and subsidies
      for meetings; to the conduct of meetings with industry representatives; and other
      matters. We believe that clearly stated guidance will benefit the biomedical
      industry and physicians alike.

PMID- 12195859
TI  - Training in the management of the acutely ill medical patient.
AB  - The care of acutely ill patients constitutes an important and increasing part of
      hospital practice. However, the care of the acutely ill by general physicians
      without adequate training in intensive care medicine is cause for concern. This
      article identifies ways in which the recognised deficiencies in the care of the
      acutely ill medical patient can be improved.

PMID- 12195860
TI  - The evolution of the hospitalist movement in the USA.
AB  - The hospitalist movement represents a novel paradigm of health care delivery in
      the USA, its evolution hastened by a variety of financial, clinical, and time
      pressures. Hospitalists are site-defined specialists who spend the majority of
      their professional time practising in the hospital, and in this respect are
      similar to emergency medicine or critical care specialists. Community hospitals
      were the sites of early growth in hospitalist systems, and academic medical
      centres quickly followed suit. The field has grown rapidly, and now has its own
      textbook, professional society, training programme, and research and educational
      agenda. Published research to date has upheld the promise of the hospitalist
      model: improving efficiency of care by reducing length of stay and hospital costs
      without compromising quality or patient satisfaction. Future hospitalist research
      will aim to elucidate the role of hospitalists in the care of critically ill and
      surgical patients, identify the competencies that will ultimately define this
      specialty, and expand our understanding of key inpatient issues, such as
      prevention of nosocomial infections, end-of-life care, and hospital quality
      measurement.

PMID- 12195861
TI  - A consultant physician in acute medicine: the Bournemouth Model for managing
      increasing numbers of medical emergency admissions.
AB  - Consultant-led medical admission units have been developed as one method of
      managing the increasing number of acute medical emergencies. The need to document
      such innovations and to evaluate and analyse the role of an acute care physician
      in meeting the problems of acute care has been emphasised. We therefore report
      our experience of an acute admissions unit led by a consultant physician in acute
      medicine in a district general hospital.

PMID- 12195862
TI  - Tobacco control policy: the European dimension.
AB  - The Royal College of Physicians has long played an important role in the struggle
      against tobacco. As tobacco is a legally traded substance, its regulation
      increasingly takes place at a European level, where governments seek to balance
      concerns about public health and free trade. Consequently, it is essential that
      those seeking to reduce the toll of tobacco-related disease understand the nature
      of the debate at a European level, in particular the strategies being pursued by
      the tobacco industry to undermine efforts to promote public health. After
      describing the European legislative process, this paper explores the current
      European debates on advertising restrictions, warning labels and cigarette
      composition, bans on public smoking, taxation, alleged industry involvement in
      smuggling, and subsidies for tobacco producers. It concludes by examining areas
      where the College might take action.

PMID- 12195863
TI  - The geography of thinking.
AB  - People in different cultures are taught to think differently. How we gather
      information, process, rationalise, justify and communicate our ideas is
      culturally determined. Europe is divided between the pragmatic, inductive
      thinking of North Sea cultures and the rationalist thinking of the rest of the
      continent. Westerners and Asians have different mental skills and capacities
      deriving from the nature of written and spoken language, the relative importance
      of learning by rote or investigation and the social environment. Western children
      are expected to ask questions and test ideas for themselves, while in Asia it is
      unacceptable to question anyone senior in age or authority, including teachers.
      Westerners base thinking on reason; Asians base thinking on harmony. Whenever
      people of different cultures work together, different ways of thinking create
      barriers to understanding and communication. This applies to many spheres of
      work, including the medical profession.

PMID- 12195864
TI  - Doctors, patients and the search for the truth on the Internet.
AB  - The overnight availability of huge amounts of medical information from the
      internet has dramatically affected patients and doctors, and has swiftly
      highlighted a pressing need to deal with the problem of assessing the validity of
      such information. A number of further issues arise from this, most notably the
      questionable practice of selling supposed 'miracle cures' via the Internet. The
      introduction of measures that ensure the regulation of health-related websites
      has to be a priority for the health care profession. It is important not only to
      protect patients, and reduce the amount of doctors' time that is wasted, but also
      to allow confidence to develop in the reputable sites that exist. Such sites can
      provide accurate and useful information and can help to assemble supportive
      health-related communities on-line; facets that could be of great benefit to both
      patients and doctors alike.

PMID- 12195865
TI  - Intensive care monitoring: past, present and future.
AB  - Monitoring is the serial evaluation of time-stamped data, and the volume of such
      data in an intensive care unit is huge. Clinical and biochemical data may be
      available at hourly or more frequent intervals but physiological data are
      'continuous'. Although sophisticated monitors display the physiological data in
      multiple and varied combinations, staff are challenged by the frequency of the
      false alarms and lack of knowledge of the patterns from which they could predict
      problems. All these data, together with large amounts of clinical data, lead to
      information overload. In this paper, the case is made for the development of
      automatic decision-support system based on statistical and probabilistic analysis
      of data patterns appropriate for the level of cognition of the user (nurses and
      juniors at the bedside rather than consultants). Such decision support could both
      reduce the false-positive alarms that frustrate clinical staff, and improve the
      early detection of pathophysiological events. We have used the development of a
      pneumothorax as our paradigm. Our data indicate that the clinical diagnosis of
      pneumothorax takes a median of 127 minutes, but using short decision algorithms
      based on routinely available monitoring data, most can be detected within 10-15
      minutes of occurrence.

PMID- 12195866
TI  - Oxygen homeostasis and cancer: insights from a rare disease.
AB  - Many aspects of physiology and anatomy are precisely adjusted so that the right
      amount of oxygen reaches cell throughout the body. Hypoxia-inducible factor-1
      (HIF-1) is activated by low oxygen tension in all mammalian cells and underpins
      many aspects of the impressive ability to match oxygen supply and demand. As
      examples, HIF-1 regulates: local capillary architecture via angiogenic signalling
      red cell production via erythropoietin cellular metabolism via increased
      expression of glucose transporters and glycolytic enzymes. HIF-1 is also
      important in disease, for example in cancer where it is involved in angiogenesis.
      This review describes how HIF-1 is regulated by oxygen and the central role
      played by the von Hippel-Lindau tumour suppressor protein. The underlying oxygen
      sensor is provided by a family of enzymes which oxidize specific proline residues
      in HIF alpha subunits. Inhibiting these newly discovered enzymes provides a way
      of activating HIF-1 in the presence of oxygen--an exciting prospect for
      therapeutic intervention in ischaemic diseases.

PMID- 12195867
TI  - Non consultant career grade doctors: past, present and future.

PMID- 12195868
TI  - PEGs in chronic neurological disorders.

PMID- 12195869
TI  - From aviation to clinical medicine.

PMID- 12195870
TI  - Hypertension and renal failure.

PMID- 12195871
TI  - Junior doctors' experience of percutaneous liver biopsy: a questionnaire survey.

PMID- 12195872
TI  - Beta-hemolytic streptococcal bacteremia: a review of 241 cases.
AB  - Bacteremia with beta-hemolytic Streptococci groups A, B, C and G has a mortality
      rate of approximately 20%. In this study we analyzed the association of various
      patient risk factors with mortality. Records from 241 patients with beta
      hemolytic streptococcal bacteremia were reviewed with particular attention to
      which predisposing factors were predictors of death. A logistic regression model
      found age, burns, immunosuppressive treatment and iatrogenic procedures prior to
      the infection to be significant predictors of death, with odds ratios of 1.7 (per
      decade), 19.7, 3.6 and 6.8, respectively. In bacteremic patients with erysipelas,
      mortality increased from 8% to 50% when bullae were observed. No HIV-positive
      patients or IVDUs died as a result of their bacteremic episode. Surprisingly, we
      found 49% resistance to tetracycline.

PMID- 12195873
TI  - Three days of pivmecillinam or norfloxacin for treatment of acute uncomplicated
      urinary infection in women.
AB  - Pivmecillinam is a unique beta-lactam antimicrobial that has been used for the
      treatment of acute uncomplicated urinary infection for > 20 y. Since this agent
      was introduced, the quinolone antimicrobials have become widely used for the same
      indication. This study compared the efficacy of a 3-d regimen of pivmecillinam
      400 mg b.i.d. with norfloxacin 400 mg b.i.d. Women aged between 18 and 65 y
      presenting with symptoms of acute cystitis of < 7 d duration were eligible for
      enrollment; 483 were randomized to receive pivmecillinam and 471 to receive
      norfloxacin. In each group, 30% of women had negative urine cultures prior to
      therapy. Bacteriologic cure at early post-therapy follow-up was achieved in
      222/298 (75%) pivmecillinam patients and 276/302 (91%) norfloxacin patients [p <
      0.001; 95% confidence interval (CI) 12.0-21.8]. Clinical cure/improvement at Day
      4 following initiation of therapy was observed in 434/457 (95%) women who
      received pivmecillinam and 425/442 (96%) who received norfloxacin (p = 0.39; 95%
      CI 1.5-3.9). Early post-therapy (11 +/- 2 d) clinical cure was achieved in
      360/437 women (82%) who received pivmecillinam and 381/433 (88%) who received
      norfloxacin (p = 0.019; 95% CI 0.9-10.3). In women aged < or = 50 y, early
      clinical cure rates were 294/351 (84%) for pivmecillinam and 299/340 (88%) for
      norfloxacin (p = 0.11; 95% CI 1.0-9.4). Adverse effects were similar for both
      regimens, and there was no evidence of the emergence of organisms of increasing
      resistance with therapy. Short-course therapy with norfloxacin was superior to
      that with pivmecillinam in terms of bacteriologic outcome, although differences
      in clinical outcome were less marked. In conclusion, short-course therapy with
      pivmecillinam is an effective empirical treatment for pre-menopausal women.

PMID- 12195874
TI  - Proinflammatory cytokines, antibodies to Chlamydia pneumoniae and age-associated
      diseases in Danish centenarians: is there a link?
AB  - Plasma levels of tumour necrosis factor (TNF)-alpha levels increase with age.
      High levels are associated with dementia and atherosclerosis in centenarians.
      Chlamydia pneumoniae induces the production of proinflammatory cytokines and has
      been related to the pathogeneses of Alzheimer's disease and cardiovascular
      diseases. The purpose of this study was to test the hypothesis that circulating
      levels of TNF-alpha represent a link between C. pneumoniae, high prevalences of
      dementia and cardiovascular diseases in 126 Danish centenarians. IgA antibody
      titres against C. pneumoniae were linearly correlated with high plasma levels of
      TNF-alpha in centenarians. However, both parameters were also correlated with
      total IgA in the blood and the association between C. pneumoniae IgA and TNF
      alpha was not significant when total IgA was included in a multiple linear
      regression model. Accordingly, the association between C. pneumoniae-specific IgA
      and TNF-alpha may reflect immune activation rather than a specific antibody
      response. No associations were found between antibodies to C. pneumoniae and
      dementia or cardiovascular diseases. Although TNF-alpha is likely to be involved
      in the pathogenesis of atherosclerosis and dementia, the present study does not
      support the hypothesis that TNF-alpha represents a link between chronic C.
      pneumoniae infection and these disorders.

PMID- 12195875
TI  - Hepatocyte growth factor may act as an early therapeutic predictor in pneumonia.
AB  - High serum levels of hepatocyte growth factor (HGF) may reflect the regenerative
      effect and enhanced local and systemic production of this cytokine after organ
      injuries. The possibility of using serial serum HGF values in order to predict
      the results of therapy for pneumonia was investigated in this study. In a
      prospective multicenter study we investigated the serum levels of HGF and CRP
      before and within 48 h after treatment in 70 patients with pneumonia. Serum
      levels of HGF before treatment were significantly higher than the HGF levels of a
      normal population (p < 0.0001). Within 48 h serum HGF levels had decreased
      significantly in those patients who ultimately responded to the initial
      antibiotic therapy (p < 0.0001). Serum HGF levels at 48 h were unchanged or
      increased in cases in whom the initial therapy was ineffective and had to be
      changed. CRP and HGF levels were significantly correlated. Using multivariate
      logistic regression analysis it was found that individual changes in acute serum
      HGF levels and serum HGF levels obtained within 48 h could predict the results of
      therapy at least as significantly (p < 0.003) as CRP (p = 0.05), although CRP
      levels were known and used by the physician to decide whether or not to change
      the initial therapy. We conclude that serial control of serum HGF levels can be
      used as an early indicator to predict the results of therapy during treatment of
      pneumonia.

PMID- 12195876
TI  - Lamivudine and famciclovir combination therapy with or without addition of
      interferon-alpha-2b for HBeAg-positive chronic hepatitis B: a pilot study.
AB  - Lamivudine and famciclovir combination therapy has been used in patients with
      chronic HBeAg-positive hepatitis B to enhance the antiviral effect and reduce the
      risk of development of resistance. Interferon-alpha (IFN-alpha) can theoretically
      be added to the regimen to further improve the antiviral effect. Twenty patients
      with HBeAg-positive chronic hepatitis B were given lamivudine and famciclovir
      combination therapy for 24 weeks. After 12 weeks of treatment, patients were
      randomized on a 1:1 basis to either the addition of IFN-alpha 2b or no addition
      for the last 3 months of therapy. The decline in HBV DNA levels, the loss of
      HBeAg and the HBeAg seroconversion rate were assessed. Patients with loss of
      HBeAg and/or development of anti-HBe were followed up for at least 1 y after
      stopping treatment. Four of 19 patients (21%) had lost HBeAg and/or developed
      anti-HBe 24 weeks after stopping treatment, 1 of whom had received additional IFN
      alpha. During long-term follow-up post-treatment, 2/19 patients (10.5%) had a
      durable HBeAg seroconversion. The mean HBV DNA level declined by 5 logs during
      the first 12 weeks of treatment. Addition of IFN-alpha during the last 3 months
      of treatment did not result in any further decline in HBV DNA levels compared
      with the non-IFN-alpha-treated group, nor in any increase in the HBeAg
      seroconversion rate. In conclusion, lamivudine and famciclovir combination
      treatment induced seroconversion from HBeAg to anti-HBe in 4/19 patients, 2 of
      whom became long-term responders. Addition of IFN-alpha did not improve the
      seroconversion rate.

PMID- 12195877
TI  - Antibiotics differ in their tendency to cause infusion phlebitis: a prospective
      observational study.
AB  - Intravenous administration of antibiotics is a known risk factor for infusion
      phlebitis. We have previously demonstrated differences in cell toxicity for 4
      antibiotics. Clinical experience indicates that antibiotics differ in their
      tendency to cause phlebitis. The present study was done prospectively on 550
      patients with 1386 peripheral venous catheters. The incidence of phlebitis was
      18.5% with antibiotics and 8.8% without (odds ratio 2.34). Dicloxacillin (odds
      ratio 5.74) and erythromycin (odds ratio 5.33) had the greatest tendency to cause
      phlebitis in univariate, multivariate and Cox regression analyses.
      Benzylpenicillin, cefuroxime and cloxacillin were also associated with a greater
      risk of phlebitis, whereas ampicillin, imipenem/cilastatin, clindamycin,
      netilmicin and vancomycin were not. Other risk factors were the site of insertion
      and age 51-60 y. Medication with warfarin was found to be protective, but not
      with aspirin. Treatment with low molecular weight heparin reduced the risk of
      phlebitis, but the difference was not significant. With regard to when
      antibiotics were given, the day-specific risk increased between Days 1 and 2, but
      no further on subsequent days. The hypothesis that antibiotics differ in their
      tendency to cause phlebitis was confirmed.

PMID- 12195878
TI  - Survival of patients with bacteraemia in relation to initial empirical
      antimicrobial treatment.
AB  - Our objective was to determine the impact on mortality of the coverage and
      spectrum of initial empirical antimicrobial treatment among bacteraemic patients
      in the county of Northern Jutland, Denmark. Patients aged > 15 y from the
      bacteraemia register who had their first episode of bacteraemia between 1996 and
      1998 were retrospectively included. Outcome was defined as survival from the day
      that the first positive blood culture was taken. Follow-up was 180 d. Survival
      probability was estimated using a Cox proportional hazard model. Conservative
      treatment was defined as penicillin G, ampicillin or similar, methicillin or
      similar, metronidazole, sulfamethoxazole, trimethoprim or a combination of these.
      We studied 2058 primary episodes of bacteraemia. The distribution of empirical
      antimicrobial treatments was: conservative/covered, 25.8%; non
      conservative/covered, 36.9%; conservative/did not cover, 16.0%; non
      conservative/did not cover, 4.8%; and no antimicrobial, 16.5%. After adjusting
      for risk factors, patients receiving a treatment that covered the
      microorganism(s) had an increased survival (relative risk [RR] = 0.50 [0.32
      0.77]; p = 0.002). Among covered episodes, receiving a conservative treatment
      significantly increased survival (RR = 0.69 [0.54-0.88]; p = 0.002). This study
      confirms that appropriate empirical antimicrobial treatment increases the
      survival of bacteraemic patients. Furthermore, conservative treatment was
      associated with a longer survival among patients covered by empirical therapy.

PMID- 12195879
TI  - Cell-associated HIV DNA measured early during infection has prognostic value
      independent of serum HIV RNA measured concomitantly.
AB  - Using data from the Danish AIDS Cohort of HIV-infected homosexual men established
      in the 1980s, the prognostic value of early HIV DNA loads was evaluated. In
      addition to DNA measurements, concomitant serum HIV RNA levels, CD4 cell counts
      and CCR5 genotypes were determined. The patients were divided into 3 groups,
      according to whether their cell-associated HIV DNA load was < or = 100, 500 or >
      or = 2,500 DNA copies/10(6) peripheral blood mononuclear cells. Clinical
      progression rates differed significantly between the groups (p < 0.005). Cell
      associated HIV DNA load had prognostic value independent of serum HIV RNA (p <
      0.02). However, when HIV DNA, HIV RNA and CD4 cell counts were all included in a
      Cox model, only serum HIV RNA had independent prognostic value. Patients
      heterozygous for the CCR5 delta 32 allele had significantly lower HIV DNA loads
      than those homozygous for the normal allele (p < 0.05). The interplay between HIV
      RNA and DNA levels is discussed, together with the possibility that cell
      associated HIV DNA load is a marker of the HIV RNA peak seen shortly after
      primary HIV infection.

PMID- 12195881
TI  - Severe thrombocytopenic purpura due to brucellosis.
AB  - A case of severe thrombocytopenic purpura as the sole manifestation of
      brucellosis in an 11-y-old boy is presented. Clinical examination was negative
      and laboratory tests revealed anemia, leukopenia and severe thrombocytopenia. The
      initial diagnosis was idiopathic thrombocytopenic purpura and intravenous gamma
      globulin was given. A prompt hematological response was observed. However, on the
      fifth day after admission, blood culture yielded Brucella which could not be
      serotyped. The boy was subsequently treated with intravenous gentamicin, oral
      doxycycline and rifampicin and was discharged in good health. Brucellosis has
      occasionally been associated with mild hematological abnormalities such as anemia
      and leukopenia. Thrombocytopenia is rare and only in very rare cases it is severe
      enough to cause bleeding. Prompt recognition of this complication of brucellosis
      and aggressive therapy are essential, especially if there is a family history of
      brucellosis or if there is suspicion of exposure to infected food products.

PMID- 12195880
TI  - Early-onset neonatal sepsis caused by vertical transmission of Morganella
      morganii.
AB  - The onset of Morganella morganii infection within the first 72 h after birth has
      only been reported on 1 occasion. The authors describe a second case in which M.
      morganii was cultured from both the neonate's blood and the mother's lochia. The
      infant was successfully treated with cefotaxime and gentamicin.

PMID- 12195882
TI  - Malakoplakia of the lung caused by Pasteurella multocida in a patient with AIDS.
AB  - We present a case of malakoplakia of the lung caused by Pasteurella multocida in
      a patient with AIDS. This is the first report to implicate P. multocida in the
      pathogenesis of malakoplakia.

PMID- 12195883
TI  - Isolated cervical lymphadenopathy as unique manifestation of Brucellosis.
AB  - We report the case of a 42-y-old male with an isolated cervical lymphadenopathy
      due to Brucella melitensis. The diagnosis was established by isolation of B.
      melitensis in a lymphatic specimen obtained by fine-needle aspiration and
      confirmed by serological test results showing high levels of Brucella
      agglutinins. Mycobacteria-specific cultures were negative. Treatment with
      streptomycin and doxycycline resulted in complete healing. Exceptionally, and
      only if the epidemiologic context supports it, brucellosis should be considered
      in the differential diagnosis of lymphadenopathy.

PMID- 12195884
TI  - Brucellosis in immigrants in Denmark.
AB  - Brucellosis is a rarely encountered infection in northern Europe. We report 4
      cases of Brucella abortus bacteremia occurring in Denmark during 1999-2000. The
      clinical presentation was characteristically vague and brucellosis was not
      suspected by the attending physicians, partly because incomplete patient
      histories were obtained as a result of language barriers. The diagnosis was
      finally established by means of blood cultures, which were performed because of
      fever of unknown origin.

PMID- 12195885
TI  - Cryptococcal meningitis in a neonate.
AB  - A case of cryptococcal meningitis in a neonate born to an HIV-negative women is
      described. The cryptococcal infection was proved using standard microbiological
      and antigen detection techniques. Although cryptococcal meningitis has previously
      been described in both immunocompromised and immunocompetent children, the
      present case represents youngest case of cryptococcosis reported to date.

PMID- 12195886
TI  - Fusobacterium necrophorum: a rare cause of meningitis in children.
AB  - We report a case of non-fatal meningitis secondary to suppurative otitis media in
      a previously healthy young boy. Fusobacterium necrophorum was isolated from
      blood; spinal fluid was cultured aerobically only but yielded no growth. After
      treatment with intravenous antibiotics and surgery the patient recovered, with a
      mild sequela of hypoglossus paresis.

PMID- 12195887
TI  - Winterbottom's sign and hypertrophic cardiomyopathy.
AB  - We present the case of a patient who presented with hypertrophic cardiomyopathy,
      generalized lymphadenopathy and serological evidence of African sleeping sickness
      (Trypanosoma gambiense). He made a full recovery after intravenous administration
      of eflornithine, a drug that is no longer distributed for antiparasitic
      indications for pharmacoeconomic reasons.

PMID- 12195889
TI  - A Scandinavian case of domestically acquired human fascioliasis.
AB  - A 30-y-old farmhand was admitted to our clinic in September 2000 with a 6-week
      history of increasing fatigue and polydipsia/polyuria after an initial short
      spell of gastroenteritis. No evidence of disease was discovered. During follow-up
      he developed leucocytosis with prominent eosinophilia, leading to the discovery
      of multiple liver abscesses and subsequently to the diagnosis of human
      fascioliasis of domestic origin. Although not uncommon in Europe, the infestation
      has hitherto not been reported from Scandinavia. The patient was successfully
      treated with praziquantel.

PMID- 12195888
TI  - Acute renal failure as initial presentation of visceral leishmaniasis in an HIV-1
      infected patient.
AB  - We report the case of an HIV-infected patient who presented with acute renal
      failure due to visceral leishmaniasis (VL). Although renal failure is the leading
      cause of death in dogs, the natural reservoir of Leishmania infantum, renal
      involvement is usually absent in human VL. However, L. infantum can be considered
      a cause of renal failure in HIV-infected patients.

PMID- 12195890
TI  - Successful tolerance induction to spiramycin in pregnancy.
AB  - We report the cases of 2 pregnant patients, suffering from toxoplasmosis, who
      developed an erythematous, maculopapular rash during spiramycin therapy that
      disappeared with discontinuation of the drug. The 2 patients underwent a
      tolerance induction protocol with spiramycin and were able to continue therapy
      with this drug until the end of their pregnancies, with no side-effects.

PMID- 12195891
TI  - Cutaneous tuberculosis: an evaluation of 7 cases.

PMID- 12195892
TI  - Polyfungal candidaemia due to Candida rugosa and Candida pelliculosa in a
      haemodialyzed neonate.

PMID- 12195894
TI  - Too posh to push? Cesarean sections have spiked dramatically. Progress or
      convenience?

PMID- 12195893
TI  - Cruel and usual.

PMID- 12195895
TI  - Criminal care at a high price. More prisoners are sicker than ever. And you're
      paying for their medical bills.

PMID- 12195896
TI  - Wrenching genes. New insights into a rare disorder may illuminate the biology
      behind a range of mental problems.

PMID- 12195897
TI  - Hitting teen smokers where it hurts: in the wallet.

PMID- 12195898
TI  - Making a stink. Neighbors say sewage sludge fertilizer makes them ill.

PMID- 12195899
TI  - A curse to last 10,000 years. A nuclear-waste dump needs a 'keep out' sign with a
      long half-life.

PMID- 12195900
TI  - Blood on the home front.

PMID- 12195901
TI  - Fish tale.

PMID- 12195902
TI  - Why Tai Chi is the perfect exercise.

PMID- 12195903
TI  - Code of conduct: a much-needed reminder.

PMID- 12195904
TI  - Radiologic case study. Osteochonditis dissecans of the capitellum.

PMID- 12195905
TI  - Reduction of an angled displacement using the Ilizarov apparatus.

PMID- 12195906
TI  - Changes in patellar tracking after total knee arthroplasty: 10-year follow-up of
      Miller-Galante I knees.
AB  - Changes in patellar tilt angle and patellar displacement were evaluated in 18
      knees with the Miller-Galante I knee arthroplasty system (Zimmer, Warsaw, Ind).
      Mean follow-up was 10 years. Patellar tilt angle at final follow-up (5.7 degrees)
      was significantly larger than at 1 year postoperatively (2.8 degrees). Patellar
      displacement at final follow-up (5.1 mm) was significantly larger than at 1 year
      postoperatively (3.4 mm). Preoperatively, patellar tilt angle showed a
      statistically significant correlation with the change in tilting angle during
      follow-up. These results suggest patellar tracking can worsen during the long
      term postoperative period.

PMID- 12195907
TI  - Scaphoid fractures: dorsal versus volar approach.
AB  - Twenty-six patients with scaphoid fractures were treated with internal fixation
      using a cannulated differential pitch compression screw. Sixteen patients
      underwent a dorsal approach (group 1) 10 patients a volar approach (group 2).
      Average time from injury to surgery was 6.6 months (range: 0.3-19 months) for
      group 1 and 8.3 months (range: 0.3-24 months) for group 2. The rate of union,
      determined by radiographs and clinical examination, was 81% in group 1 and 80% in
      group 2. No significant differences were noted between the groups for
      dorsiflexion/palmar flexion, radial deviation, grip strength, and pain level.

PMID- 12195908
TI  - Piriformis syndrome.
AB  - Seven patients underwent release of the piriformis from the femur. Patients with
      residual symptoms after conservative treatment had dramatic relief of sciatica
      and 70% resumed customary work after surgery. Minimum follow-up was 31 months
      (average: 51 months). Early diagnosis can avoid prolonging ineffective empiric
      treatment and disability with satisfactory results achieved in most patients by
      conservative treatment and relief of sciatica in selected surgical cases.

PMID- 12195910
TI  - Ultrasonography of the infant hip: the significance of provokable instability
      with normal morphology.
AB  - The hips of infants 2- to 4-weeks-old were investigated with ultrasonography. In
      all cases, ultrasonography verified morphologically normal hips; however, either
      a bilateral or unilateral instability of the hip could be provoked as
      demonstrated by ultrasonography. The first series of 27 infants (41 hips) were
      treated with abduction splint (Frejkas pillow) for 16 weeks. The second series of
      28 infants (44 hips) were left untreated. All infants had repeat ultrasonography
      at 2 and 16 weeks and radiographs at 16 weeks. At 2 weeks, provokable instability
      was still seen in 10 hips in the treated group and 12 hips in the untreated
      group. At 16 weeks, all hips were ultrasonographically stable. The morphology was
      evaluated by alpha and beta angles by ultrasonography and also acetabular index
      by radiographs at 16 weeks. In all cases, normal hip development was noted with
      no differences between the two groups. Therefore, sonographically, instability in
      morphologically normal or immature hips has no clinical significance.

PMID- 12195909
TI  - Coccidioides immitis osteomyelitis: a case series review.
AB  - A retrospective chart review and telephone follow-up was conducted on patients
      who were treated for disseminated coccidioidomycosis involving bones or joints at
      the Naval Medical Center, San Diego, California from 1993-1999. Thirteen patients
      were identified, with average follow-up of 36 months. Six patients underwent
      surgical debridement and systemic medical therapy, and seven patients were
      treated medically only. All patients improved symptomatically with decreasing
      complement fixation titers at last follow-up. Five of the six patients treated
      with combined therapy are currently quiescent. Of those treated medically, four
      patients are quiescent; three were lost to follow-up. Coccidioidomycosis
      osteomyelitis remains a rare but difficult disease to treat, with a lifelong risk
      of recurrence. A combined medical and surgical approach has been shown to be
      effective, but medical therapy alone with intravenous amphotericin B followed by
      suppressive azole therapy may be effective in selected patients.

PMID- 12195911
TI  - Periosteal chondrosarcoma.

PMID- 12195912
TI  - Denervation of the sinus tarsi for chronic post-traumatic lateral ankle pain.

PMID- 12195913
TI  - Repair of a subscapular tear in a 13-year-old boy.

PMID- 12195914
TI  - Fracture of a three peg, nonmetal-backed, polyethylene patellar component.

PMID- 12195915
TI  - Tibial plateau fracture.

PMID- 12195916
TI  - Localized cortical bone absorption induced by cubital bursitis in rheumatoid
      arthritis.

PMID- 12195917
TI  - Epidermoid cyst of the thumb.

PMID- 12195918
TI  - Anterior cruciate ligament injuries in skeletally immature patients.

PMID- 12195919
TI  - And now for a hot flash.

PMID- 12195920
TI  - Creativity under the gun.
AB  - If you're like most managers, you've worked with people who swear they do their
      most creative work under tight deadlines. You may use pressure as a management
      technique, believing it will spur people on to great leaps of insight. You may
      even manage yourself this way. If so, are you right? Not necessarily, these
      researchers say. There are instances where ingenuity flourishes under extreme
      time pressure--for instance, a NASA team within hours comes up with a primitive
      but effective fix for the failing air filtration system aboard Apollo 13. But
      when creativity is under the gun, it usually ends up getting killed, the authors
      say. They recently took a close look at how people experience time pressure,
      collecting and analyzing more than 9,000 daily diary entries from individuals who
      were working on projects that required high levels of creativity and measuring
      their ability to innovate under varying levels of time pressure. The authors
      describe common characteristics of time pressure and outline four working
      environments under which creativity may or may not flourish. High-pressure days
      that still yield creativity are full of focus and meaningful urgency--people feel
      like they are on a mission. High-pressure days that yield no creativity lack such
      focus--people feel like they are on a treadmill, forced to switch gears often. On
      low-pressure days that yield creativity, people feel like they are on an
      expedition--exploring ideas rather than just identifying problems. And on low
      pressure days that yield no creative thinking, people work on autopilot--doing
      their jobs without engaging too deeply. Managers should avoid extreme time
      pressure when possible; after all, complex cognitive processing takes time. For
      when they can't, the authors suggest ways to mollify its effects.

PMID- 12195921
TI  - The failure-tolerant leader.
AB  - "The fastest way to succeed," IBM's Thomas Watson, Sr., once said, "is to double
      your failure rate." In recent years, more and more executives have embraced
      Watson's point of view, coming to understand what innovators have always known:
      Failure is a prerequisite to invention. But while companies may grasp the value
      of making mistakes at the level of corporate practices, they have a harder time
      accepting the idea at the personal level. People are afraid to fail, and
      corporate culture reinforces that fear. In this article, psychologist and former
      Harvard Business School professor Richard Farson and coauthor Ralph Keyes discuss
      how companies can reduce the fear of miscues. What's crucial is the presence of
      failure-tolerant leaders--executives who, through their words and actions, help
      employees overcome their anxieties about making mistakes and, in the process,
      create a culture of intelligent risk-taking that leads to sustained innovation.
      Such leaders don't just accept productive failure, they promote it. Drawing from
      their research in business, politics, sports, and science, the authors identify
      common practices among failure-tolerant leaders. These leaders break down the
      social and bureaucratic barriers that separate them from their followers. They
      engage at a personal level with the people they lead. They avoid giving either
      praise or criticism, preferring to take a nonjudgmental, analytical posture as
      they interact with staff. They openly admit their own mistakes rather than trying
      to cover them up or shifting the blame. And they try to root out the destructive
      competitiveness built into most organizations. Above all else, failure-tolerant
      leaders push people to see beyond traditional definitions of success and failure.
      They know that as long as a person views failure as the opposite of success,
      rather than its complement, he or she will never be able to take the risks
      necessary for innovation.

PMID- 12195923
TI  - The discipline of innovation. 1985.
AB  - How much of innovation is inspiration, and how much is hard work? The answer lies
      somewhere in the middle, says management thinker Peter Drucker. In this HBR
      classic from 1985, he argues that innovation is real work that can and should be
      managed like any other corporate function. Success is more likely to result from
      the systematic pursuit of opportunities than from a flash of genius. Indeed, most
      innovative business ideas arise through the methodical analysis of seven areas of
      opportunity. Within a company or industry, opportunities can be found in
      unexpected occurrences, incongruities of various kinds, process needs, or changes
      in an industry or market. Outside a company, opportunities arise from demographic
      changes, changes in perception, or new knowledge. There is some overlap among the
      sources, and the potential for innovation may well lie in more than one area at a
      time. Innovations based on new knowledge tend to have the greatest effect on the
      marketplace, but it often takes decades before the ideas are translated into
      actual products, processes, or services. The other sources of innovation are
      easier and simpler to handle, yet they still require managers to look beyond
      established practices, Drucker explains. The author emphasizes that innovators
      need to look for simple, focused solutions to real problems. The greatest praise
      an innovation can receive is for people to say, "That's so obvious!" Grandiose
      ideas designed to revolutionize an industry rarely work. Innovation, like any
      other endeavor, takes talent, ingenuity, and knowledge. But Drucker cautions that
      if diligence, persistence, and commitment are lacking, companies are unlikely to
      succeed at the business of innovation.

PMID- 12195922
TI  - Breaking out of the innovation box.
AB  - In most companies, investments in innovation follow a boom-bust cycle. For a
      time, the cash flows. Then, as the economy sours or companies rethink their
      priorities, the taps go dry. But when research budgets are slashed, the strong
      projects are often abandoned along with the weak ones. Promising initiatives are
      cut off just when they are about to bear fruit. Expensive labs are closed;
      partnership agreements costing millions in legal fees are thrown away. When
      disruptive changes in the competitive landscape come, companies are caught flat
      footed. Sustainable innovation requires a new approach: Instead of being largely
      isolated projects, innovation initiatives need to gain access to the insights and
      capabilities of other companies. To be protected from the ax of short-term cost
      reductions and the faddishness born of easy money, the initiatives must become
      part of the ongoing commerce that takes place among companies. But how can
      businesses traffic in such sensitive information without giving their competitors
      an advantage? The answer, the author contends, lies in a practice that's been
      common since the Middle Ages: the use of independent intermediaries to facilitate
      the exchange of sensitive information among companies without revealing the
      principals' identities or motives and without otherwise compromising their
      interests. Executive search firms, for example, allow job seekers to remain
      anonymous during the early stages of a search, and they protect businesses from
      disclosing their hiring plans to rivals. A network of innovation intermediaries
      would be in a unique position to visualize new opportunities synthesized from
      insights and technologies provided by several companies--ideas that might never
      occur to businesses working on their own.

PMID- 12195924
TI  - West Nile: back with a vengeance.

PMID- 12195925
TI  - Food fight--carbs vs. fat.

PMID- 12195926
TI  - Drug deal.

PMID- 12195927
TI  - A miracle of science.

PMID- 12195928
TI  - The tobacco sham. New farm equipment, fighting Satan and sprinklers: how the
      states are spending their settlement money.

PMID- 12195929
TI  - Mosquito season turns deadly.

PMID- 12195930
TI  - How are we doing?

PMID- 12195931
TI  - The acute effects of tetrahydrocannabinol on auditory threshold and frequency
      resolution in human subjects.
AB  - AIMS: The study was designed to investigate the acute effects of ingested
      tetrahydrocannabinol (THC) on auditory function. METHODS: Eight male subjects
      (aged 22-30 years), who had previous experience of cannabis use, took part in
      this study. They performed air conduction pure tone audiometry in both ears over
      0.5-8 kHz. A simple test of frequency selectivity by detecting a 4-kHz tone under
      two masking noise conditions was also carried out in one ear. Three test sessions
      at weekly intervals were carried out, at the start of which they ingested a
      capsule containing either placebo, or 7.5 or 15 mg of THC. These were
      administered in a randomized cross-over, double-blind manner. Auditory testing as
      described above was carried out 2 hours after ingestion. Blood samples were also
      obtained at this time point and assayed for delta 9- and 11-OH-THC levels.
      RESULTS: No significant changes in threshold or frequency resolution were seen
      with the dosages employed in this study. CONCLUSIONS: This suggests that THC at
      the plasma levels attained in this study does not have profound effect on the
      processing of elementary stimuli by the auditory pathway.

PMID- 12195932
TI  - Yellow oleander poisoning in Sri Lanka: outcome in a secondary care hospital.
AB  - Cardiac toxicity after self-poisoning from ingestion of yellow oleander seeds is
      common in Sri Lanka. We studied all patients with yellow oleander poisoning (YOP)
      admitted to a secondary care hospital in north central Sri Lanka from May to
      August 1999, with the objective of determining the outcome of management using
      currently available treatment. Patients with bradyarrhythmias were treated with
      intravenous boluses of atropine and intravenous infusions of isoprenaline.
      Temporary cardiac pacing was done for those not responding to drug therapy.
      During the study period 168 patients with YOP were admitted to the hospital
      (male:female = 55:113). There were six deaths (2.4%), four had third-degree heart
      block and two died of undetermined causes. They died soon after delayed admission
      to the hospital before any definitive treatment could be instituted. Of the
      remaining 162 patients, 90 (55.6%) patients required treatment, and 80 were
      treated with only atropine and/or isoprenaline while 10 required cardiac pacing
      in addition. Twenty-five (14.8%) patients had arrhythmias that were considered
      life threatening (second-degree heart block type II, third-degree heart block and
      nodal bradycardia). All patients who were treated made a complete recovery. Only
      a small proportion of patients (17%) admitted with YOP developed life-threatening
      cardiac arrhythmias. Treatment with atropine and isoprenaline was safe and
      adequate in most cases.

PMID- 12195933
TI  - Promising role of alpha-ketoglutarate in protecting against the lethal effects of
      cyanide.
AB  - Treatment of cyanide poisoning generally includes amyl nitrite and/or sodium
      nitrite (SN) in combination with sodium thiosulphate (STS). However, in many
      instances of cyanide poisoning, use of nitrites is contraindicated due to their
      strong vasoactive properties. alpha-Ketoglutarate (alpha-KG) antagonizes cyanide
      poisoning by cyanohydrin formation. Protective efficacy of graded doses of alpha
      KG (p.o.) as pretreatment, simultaneous treatment or post-treatment was evaluated
      against acute potassium cyanide (KCN) poisoning (p.o.) in female rats.
      Pretreatment with alpha-KG (0.125-2.0 g/kg) exhibited dose- and time-dependent
      effects and was found to be effective even when given up to 60 min prior to KCN.
      Addition of STS significantly enhanced the protective efficacy of alpha-KG at all
      the doses and time intervals. A 10-min pretreatment with alpha-KG increased the
      LD50 of KCN by 7-fold, which was further increased 28-fold by the addition of
      both SN and STS. Simultaneous treatment with alpha-KG (2.0 g/kg) increased the
      LD50 of KCN by 7-fold, which was doubled by the addition of STS. However,
      addition of SN did not confer any additional protection. Post-treatment with
      alpha-KG + STS minimized the mortality by 50% but did not significantly extend
      the survival time in KCN (2 LD50)-administered rats. KCN (0.75 LD50) inhibited
      rat brain cytochrome oxidase, which was significantly protected by pretreatment
      or simultaneous treatment with alpha-KG and STS. Considering the efficacy and
      safety of peroral alpha-KG, a promising treatment regimen consisting of alpha-KG
      + STS or alpha-KG + SN + STS is proposed depending upon the situation.

PMID- 12195934
TI  - An investigation of new toxicity test method performance in validation studies:
      1. Toxicity test methods that have predictive capacity no greater than chance.
AB  - An approach commonly used to measure new toxicity test method (NTM) performance
      in validation studies is to divide toxicity results into positive and negative
      classifications, and the identify true positive (TP), true negative (TN), false
      positive (FP) and false negative (FN) results. After this step is completed, the
      contingent probability statistics (CPS), sensitivity, specificity, positive
      predictive value (PPV), and negative predictive value (NPV) are calculated.
      Although these statistics are widely used and often the only statistics used to
      assess the performance of toxicity test methods, there is little specific
      guidance in the validation literature on what values for these statistics
      indicate adequate performance. The purpose of this study was to begin developing
      data-based answers to this question by characterizing the CPS obtained from an
      NTM whose data have a completely random association with a reference test method
      (RTM). Determining the CPS of this worst-case scenario is useful because it
      provides a lower baseline from which the performance of an NTM can be judged in
      future validation studies. It also provides an indication of relationships in the
      CPS that help identify random or near-random relationships in the data. The
      results from this study of randomly associated tests show that the values
      obtained for the statistics vary significantly depending on the cut-offs chosen,
      that high values can be obtained for individual statistics, and that the
      different measures cannot be considered independently when evaluating the
      performance of an NTM. When the association between results of an NTM and RTM is
      random the sum of the complementary pairs of statistics (sensitivity +
      specificity, NPV + PPV) is approximately 1, and the prevalence (i.e., the
      proportion of toxic chemicals in the population of chemicals) and PPV are equal.
      Given that combinations of high sensitivity-low specificity or low specificity
      high sensitivity (i.e., the sum of the sensitivity and specificity equal to
      approximately 1) indicate lack of predictive capacity, an NTM having these
      performance characteristics should be considered no better for predicting
      toxicity than by chance alone.

PMID- 12195935
TI  - An investigation of new toxicity test method performance in validation studies:
      2. Comparison of three measures of toxicity test performance.
AB  - An area that requires further research is how best to measure test method
      performance in validation studies and how to set criteria that should be used to
      judge the adequacy of this performance. The studies reported here were designed
      to begin an investigation of these questions. Computer simulations were used to
      generate data sets similar to those that might be obtained from a large
      validation study. These data were then analysed using three procedures including
      determination of the 95% prediction interval (PI), calculation of Pearson's
      correlation coefficient and calculation of the contingent probability statistics
      (CPS), sensitivity, specificity, positive predictive value (PPV), and negative
      predictive value (NPV). The results of this work suggest that of the three
      approaches examined, quantitative measurements with calculation of the 95% PI
      provide the most information to allow discrimination between the performance of
      several different NTMs. The results also suggest that dividing data sets into
      positive and negative toxicity classifications followed by the calculation of CPS
      leads to considerable information loss. This loss of information may be so
      significant that it is not possible in certain circumstances to distinguish
      between NTMs that are adequate and those that are not.

PMID- 12195936
TI  - An investigation of new toxicity test method performance in validation studies:
      3. Sensitivity and specificity are not independent of prevalence or distribution
      of toxicity.
AB  - Often, the only measures of toxicity test performance provided in validation
      studies are the contingent probability statistics (CPS) sensitivity, specificity,
      positive predictive value (PPV), and negative predictive value (NPV). Sensitivity
      and specificity are generally used in preference to NPV and PPV since NPV and PPV
      are assumed to vary with changes in prevalence while sensitivity and specificity
      are assumed to be independent of changes in prevalence. The purpose of the
      studies reported here was to test whether or not sensitivity and specificity are
      actually independent of changes in prevalence. Results derived from these studies
      indicate that sensitivity and specificity vary significantly depending on the
      prevalence of toxic substances in the set of chemicals being tested. This means
      sensitivity and specificity should not always be considered constant indicators
      of toxicity test performance.

PMID- 12195939
TI  - Pulsed amperometric detection of carbohydrates on an electrophoretic microchip.
AB  - The first report of pulsed amperometric detection (PAD) on an electrophoretic
      microchip is presented. A hybrid poly-(dimethylsiloxane)/glass device was coupled
      with a platinum working electrode for the electrochemical detection of glucose,
      maltose, and xylose. Under optimized detection conditions, glucose was found to
      respond linearly from 20 to 500 microM with a measured detection limit of 20
      microM. The coupling of PAD with a microchip provides a straightforward approach
      to the analysis of a wide range of carbohydrates using microfluidics.

PMID- 12195937
TI  - Flow cytometric detection of apoptotic bone marrow cells with fractional DNA
      content after application of WR-2721, cyclophosphamide, cisplatin, and exposure
      of mice to gamma rays.
AB  - Little is known about the mechanisms of apoptosis triggered in normal cells of
      the haemopoietic system by the aminothiol WR-2721 (Amifostine), chemotherapeutic
      drugs, and ionizing radiation; thus, the present study was undertaken to evaluate
      the effects of WR-2721, cyclophosphamide (CP), cisplatin (CDDP), and 60Co gamma
      rays on induction of apoptotic DNA degradation in bone marrow cells. Adult male
      Swiss mice were treated with WR-2721 (400 mg/kg b.wt.), CP (200 mg/kg b.wt.), and
      CDDP (10 mg/kg b.wt.), and exposed to 6 Gy 60Co gamma rays. Alterations in the
      number of apoptotic cells with fractional DNA content and also the cell cycle
      position of the non-apoptotic cells were determined in the bone marrow at 7 and
      24 hours after treatment of mice with these agents, using flow cytometric assay
      of the controlled extraction of low-MW DNA from apoptotic cells. The
      chemotherapeutic drugs CP and CDDP and 60Co gamma rays triggered apoptosis and
      affected the cell cycle position of the non-apoptotic cells in the mouse bone
      marrow. The pretreatment of mice with WR-2721 resulted in the modulatory action
      of the aminothiol on induction of apoptotic cell death and changes in the cell
      cycle distribution of the non-apoptotic cells caused by the DNA-damaging agents.
      The patterns of changes in the frequency of apoptotic cells and the cell cycle
      position of the non-apoptotic cells, observed in the bone marrow, were dependent
      on the agent(s) applied and the time interval after application of the drug(s)
      and exposure of mice to gamma rays. Understanding of the mechanisms responsible
      for triggering of apoptotic cell death and disturbing of the cell cycle by the
      DNA-damaging agents, and modulation of the apoptotic and cell cycle pathways by
      the aminothiol WR-2721, can lead to more effective therapy and chemo- and radio
      protection of normal cells.

PMID- 12195938
TI  - The pharmacologic stability of 35-year old theophylline.
AB  - The propensity to preserve and to hoard drugs over the years at home is a well
      known phenomenon and offers the possibility for intentional and accidental drug
      poisoning in man. We report a case of acute theophylline poisoning in an 80-year
      old women after ingestion of 'Asthmo-Kranit', a 35-year old combined preparation
      containing theophylline and aminopyrine as the main ingredients. The patient
      developed the typical clinical picture of a symptomatic theophylline poisoning
      with flush, tremor, tachycardia, hyperventilation, hypotonia, and hyperglycaemia.
      The clinical course after treatment with beta-blockers was without complications.
      The determination of theophylline in tablets showed stability of 90% of the
      labelled amount of the drug 30 years beyond the expiration date. The case
      illustrates the prolonged shelf stability and pharmacological potency of some
      pharmaceuticals and points to the risk of long-outdated prescriptions. Physicians
      should primarily not underestimate drug toxicity in consequence of old-age
      pharmaceuticals.

PMID- 12195940
TI  - Molecular imprinted polymer coated QCM for the detection of nandrolone.
AB  - An acoustic wave sensor coated with an artificial biomimetic recognition element
      has been developed to selectively screen for nandrolone in the liquid phase. A
      highly specific covalently imprinted polymer (MIP) was spin coated onto one
      electrode of a quartz crystal microbalance (QCM) as a thin permeable film.
      Selective rebinding of the nandrolone was observed as a frequency shift in the
      QCM for concentrations up to 0.2 ppm with the sensor binding shown to favour
      nandrolone over analogous compounds.

PMID- 12195941
TI  - LC-electron capture APCI-MS for the determination of nitroaromatic compounds.
AB  - The determination of selected nitroaromatic compounds in liquid chromatography
      mass spectrometry with electron capture (EC) ionisation using a commercial
      atmospheric pressure chemical ionisation (APCI) interface in the negative mode is
      described. The electron capture effect is observed for nitroaromatics which do
      not easily undergo deprotonation under these conditions. Depending on the
      structure of the analytes, either dissociative or, for the first time in LC-MS,
      non-dissociative electron capture is observed. Limits of detection and linear
      range for the determination of the analytes match those obtained for
      nitroaromatics which undergo deprotonation. The investigated substances comprise
      numerous substituted nitrobenzenes and nitrobenzooxadiazoles.

PMID- 12195942
TI  - Use of non-ionic surfactant solutions for the extraction and preconcentration of
      phenolic compounds in water prior to their HPLC-UV detection.
AB  - A simple and rapid HPLC method with spectrophotometric detection to determine
      phenolic compounds in water, including the 11 priority phenolic pollutants, is
      described. As they are present in low concentrations, an extraction and
      preconcentration step is necessary prior to their determination. A methodology
      based on the cloud point phenomenon is applied using the non-ionic surfactant
      oligoethylene glycol monoalkyl ether (Genapol X-080) as extractant. The optimum
      conditions for the extraction and preconcentration of phenolic derivatives have
      been established and detection limits lower than 10 micrograms L-1 were obtained
      for all studied compounds. The method has been applied to their determination in
      sea water and depurated waste water samples.

PMID- 12195943
TI  - Estimation and correction of matrix effects in gas chromatographic pesticide
      multiresidue analytical methods with a nitrogen-phosphorus detector.
AB  - The assessment of matrix effects in the quantification of organophosphorus
      pesticides in fruit and vegetables by GC-NPD, were studied applying ANCOVA.
      Calibration curves prepared in solvent were compared with calibration curves
      prepared in a blank matrix extract for eight different commodities, establishing
      whether the matrix induces systematic or proportional errors in the
      quantification of the pesticides. In such cases correction functions were
      obtained and validated by quantifying spiked samples using solvent calibrations
      and applying the correction functions to the data obtained. The results were
      compared with those obtained by quantification using matrix-matching calibrations
      and with those from 100% recovery experiments. It was found that the matrix
      effects can be avoided using the correction functions. Finally the contribution
      of the correction functions to the uncertainty of the results was estimated as
      well as their stability during a four month period.

PMID- 12195944
TI  - Trace determination of volatile sulfur compounds by solid-phase microextraction
      and GC-MS.
AB  - A method was developed for the simultaneous determination of the following nine
      volatile sulfur compounds in gas samples: carbon disulfide, carbonyl sulfide,
      ethyl sulfide, ethyl methyl sulfide, hydrogen sulfide, isopropanethiol,
      methanethiol, methyl disulfide and methyl sulfide. The target compounds were
      preconcentrated by solid-phase microextraction (SPME) and determined by gas
      chromatography combined with mass spectrometry. Experimental design was employed
      to optimize the extraction time and temperature and concurrent detection of the
      nine compounds was achieved by using an SPME fiber coated with Carboxen
      polydimethylsiloxane (75 microns). Detection limits ranged from 1 ppt (v/v) for
      carbon disulfide to 350 ppt (v/v) for hydrogen sulfide and calibration functions
      were linear up to 20 ppb (v/v) for all the compounds investigated.

PMID- 12195945
TI  - Combined cysteine and homocysteine quantitation in plasma by trap and release
      membrane introduction mass spectrometry.
AB  - Recently, a new and efficient method for total homocysteine (tHcy) quantitation
      in plasma using trap and release membrane introduction mass spectrometry (T&R
      MIMS) with a versatile removable direct introduction membrane probe (DIMP) was
      described [R. Haddad, M. A. Mendes, N. F. Hoehr and M. N. Eberlin, Analyst, 2001,
      126, 1212]. Herein we report on the use of the DIMP-T&R-MIMS technique for total
      cysteine (tCys) quantitation; hence combined tCys and tHcy quantitation in plasma
      or serum can be achieved. The method employs Cys and Hcy derivatization with
      ethyl chloroformate (after disulfide bond reduction with dithiothreitol and
      protein precipitation with trichloroacetic acid), preconcentration in a capillary
      silicone membrane, and their thermal desorption to the gas phase inside the ion
      source region of a mass spectrometer, at a point exactly between the two
      ionization filaments. Thermal desorption uses the uniform heat radiation provided
      by the two ionization filaments. The analytes are then ionized by electron
      ionization and both Cys and Hcy are quantitated by mass spectrometry using
      selected ion monitoring. For tCys quantitation, good linearity and
      reproducibility was observed for concentrations ranging from 5 to 350 microM,
      recovery was near 95%, and the limit of detection (LOD) was of 2 microM. This LOD
      is well below the mean Cys concentration in plasma, and serum samples from a
      large group of healthy people showed a mean tCys concentration of 132 +/- 45
      microM.

PMID- 12195946
TI  - Direct sampling tandem mass spectrometry (MS/MS) and multiway calibration for
      isomer quantitation.
AB  - Direct sampling tandem mass spectrometry (MS/MS) was used for the quantitation of
      mixtures of the isomers 2-, 3- and 4-ethyl pyridine. The similarity between the
      analytes and the second-order nature of MS/MS data require the use of
      multivariate calibration techniques capable of handling multiway data.
      Multilinear PLS (N-PLS) was applied here, as well as the alternative technique of
      unfolding the data and using standard two-way PLS. Particular attention was paid
      to the optimal type of spectral preprocessing. Due to the presence of
      heteroscedastic noise the logarithmic transform of the spectra prior to
      calibration gives the best results. Predictions errors of the order of 10-15%
      were obtained, which compare well with other results found in the literature.

PMID- 12195947
TI  - Multi-adsorbent preconcentration/focusing module for portable-GC/microsensor
      array analysis of complex vapor mixtures.
AB  - A small multi-adsorbent preconcentration/focusing module for a portable GC with
      microsensor-array detector designed to determine complex mixtures of volatile and
      semi-volatile organic compounds encountered in indoor working environments is
      described. Candidate adsorbents were assessed on the basis of analyte thermal
      desorption bandwidth and efficiency, chromatographic peak shape, and breakthrough
      volume against mixtures of organic compounds ranging over four orders of
      magnitude in vapor pressure. A capillary packed with just 12.3 mg of adsorbent
      material comprising Carbopack B (8 mg), Carbopack X (2.5 mg) and Carboxen 1000
      (1.8 mg) provided the best tradeoff in operating variables, while maintaining
      sufficient capacity for a 1 L air sample containing a mixture of up to 43
      compounds, each at 100 parts-per-billion, at an ambient relative humidity of up
      to 100%. On-column focusing and temperature programming were used to enhance
      chromatographic separations, and detection limits as low as 100 parts-per
      trillion were achieved for a 1 L air sample using an integrated array of polymer
      coated surface-acoustic-wave (SAW) sensors. Implications for field analysis of
      indoor air quality are emphasized.

PMID- 12195948
TI  - Array of potentiometric sensors for the analysis of creatinine in urine samples.
AB  - The development of potentiometric biosensors for creatinine based on creatinine
      iminohydrolase (E.C. 3.5.4.21) immobilized on chitosan membranes coupled to a
      nonactin based ammonium ion selective electrode is described. The response
      characteristics of three types of biosensors with the enzyme immobilized by three
      different procedures were evaluated. The biosensors with better response
      characteristics were obtained by coupling the ammonium ion selective electrodes
      to chitosan membranes with the enzyme immobilized by adsorption. The linear
      response range of these biosensors to creatinine was 10(-4) to 10(-2) M, the
      response time was between 30 and 60 s, they showed an operational lifetime of 44
      days and the slope of the response to creatinine in the first day varied between
      50 and 52 mV decade-1. An array of six potentiometric sensors, constituted by two
      creatinine biosensors and four ion selective electrodes for potassium, sodium,
      ammonium and calcium was calibrated and a multivariate model based on PLS1 for
      the response to creatinine was obtained and validated. The array was used for the
      analysis of creatinine in urine samples and the results were compared with the
      results of a clinical analysis laboratory, based on the Jaffe reaction.

PMID- 12195949
TI  - A glucose dehydrogenase biosensor as an additional signal amplification step in
      an enzyme-flow immunoassay.
AB  - Both the antibody affinity and the detectability of the label are essential in
      deciding the final characteristics of a heterogeneous immunoassay. This paper
      describes an approach to obtain a supplementary enhancement of the signal
      generated by using an enzyme label, e.g., by including the product of the
      enzymatic reaction in an additional amplification cycle during the detection step
      performed with an amperometric biosensor based on glucose dehydrogenase (GDH). An
      immunoassay format with a labelled analyte derivative that competes with the
      analyte present in the sample for a limited amount of antibody binding sites was
      employed. The beta-galactosidase label hydrolyses the substrate aminophenyl-beta
      galactopyranoside, and the generated aminophenol enters then into a
      bioelectrocatalytic amplification cycle at the GDH biosensor. The principle was
      applied for determination of 4-nitrophenol, with the best minimal concentration
      of 1.5 microM and a midpoint of the calibration of 24 microM. The potentials and
      limitations of such a system are discussed.

PMID- 12195950
TI  - Biocatalytic precipitation induced by an affinity reaction on dendrimer-activated
      surfaces for the electrochemical signaling from immunosensors.
AB  - We have developed a strategy of signal generation for immunosensors that
      transduces biospecific affinity recognition reactions into electrochemical
      signals. The cyclic voltammetric method, tracking the precipitation of insoluble
      products onto the sensing surface and the subsequent decrement in the electrode
      area, was chosen for signal registration. Precipitation of insolubilities was
      induced by the catalytic reaction of enzymes, which were labeled to the
      biospecifically attached protein or antibody molecules. As a model system for
      affinity recognition, we have investigated the functionalization of biotin groups
      to the sensing monolayer and their biospecific interactions with anti-biotin
      antibody molecules. The immunosensing interface was developed onto the dendrimer
      activated self-assembled monolayers (SAMs), as the base template for the
      functionalization of the antigen moiety and signal generation. The advantages of
      using dendrimer-activated SAMs in comparison to the plain modified thiolate SAMs
      for the sensing surface were shown in terms of sensing performances, and the
      analytical characteristics of the resulting immunosensor were examined.
      Additionally, the sensing system was applied for biotin/(strept)avidin couples,
      extending the applicability of the developed strategy.

PMID- 12195951
TI  - Determination of mercury(II) by invertase enzyme inhibition coupled with batch
      injection analysis.
AB  - The determination of mercury(II) ions at the trace level by inhibition of the
      invertase enzyme-catalysed hydrolysis of sucrose into glucose and fructose
      coupled to electrochemical batch injection analysis was investigated using two
      approaches. In the first, the glucose produced was detected by injection of 100
      microliters samples into the batch injection cell containing a platinum electrode
      modified by immobilised glucose oxidase. In the second, the glucose and fructose
      present in injected samples were oxidised directly at a copper-modified glassy
      carbon electrode. The experimental parameters were optimised and the degree of
      enzyme inhibition by mercury(II) ions under both conditions was measured. Mercury
      concentrations in the ng ml-1 range were determined by these two techniques with
      low sample and reagent consumption. Comparison is made between the two methods
      and perspectives as a screening test for field application are indicated.

PMID- 12195952
TI  - A sonotrode for electroanalysis: the determination of copper in passivating
      media.
AB  - A sonotrode consisting of a disc shaped glassy carbon electrode attached to a
      quartz rod and inserted into a drilled ultrasonic probe tip has been designed and
      used as a novel alternative to the traditional 'face on' cell arrangement where
      an ultrasonic micro-tip probe is placed opposite a glassy carbon working
      electrode. The 'single probe' arrangement is both convenient and optimised for
      electroanalysis. We first report how under ultrasonic agitation of the sonotrode
      the mass transport to the electrode surface is enhanced compared to that observed
      under silent conditions and also how the sonotrode cell geometry compares with
      the well-established 'face on' cell geometry for cobalt electrodeposition.
      Second, we will show that the new sonotrode can be used in the application for
      the determination of copper in a series of fouling media in which conventional
      silent electroanalysis fails. The passivation of the electrodes surface by
      surfactant species can be overcome by cavitationally induced streaming and/or
      erosion at the sonotrode surface with recoveries of 100% and 93.8% achieved at 42
      W cm-2 for Triton X-100 and sodium dodecyl sulfate (SDS), respectively. Other
      data indicates that the sonotrode can be successfully employed for the detection
      of copper in beer (Marston's bitter), a system known to be complex and highly
      electrode fouling and difficult to analyse using standard, silent
      electroanalytical techniques.

PMID- 12195953
TI  - Voltammetric analysis of iron oxide pigments.
AB  - Eighteen earthy and four pure synthetic pigments containing alpha-Fe2O3
      (hematite), alpha-FeOOH (goethite) and poorly crystalline Fe and Mn oxide species
      were analyzed by voltammetry of microparticles. Three natural samples were
      subjected to an interlaboratory test to evaluate the reproducibility of the
      voltammetric peak potentials and peak shapes. The results confirmed that linear
      sweep voltammetry is able to distinguish between poorly crystalline, ferrihydrite
      like oxides and well-crystalline hematite and goethite and to detect XRD
      amorphous Mn(III,IV) oxides via the peak occurrence. Voltammetry is further able
      to distinguish between pigments containing well-crystalline goethite (according
      to its structural features) and hematite (according to its particle size). The
      microsamples of primers from two baroque paintings were also analyzed by XRD and
      voltammetry and shown to be analogous to common clayey ochres.

PMID- 12195954
TI  - Cold vapour atomic fluorescence spectrometry and gas chromatography-pyrolysis
      atomic fluorescence spectrometry for routine determination of total and
      organometallic mercury in food samples.
AB  - Two procedures have been investigated for the quantification of the different
      forms of mercury in food. A two-stage procedure has been developed to determine
      firstly total inorganic and organometallic species, and then the full separation
      of all organomercury species. The procedure involves solubilisation of the
      samples using alkaline extractions or enzymolysis, followed by the extraction of
      organic mercury in an organic solvent, preferably a mixture of dichloromethane
      and hexane (3:2). For the total organic mercury determination, the organic
      extract is analysed for "total" mercury after nitric acid/peroxide digestion,
      evaporation of the solvent and detection by cold vapour-atomic fluorescence
      spectrometry. Full organomercury speciation requires a clean-up step before
      analysis of the final extract in dichloromethane by gas chromatography coupled to
      a pyrolyser and an atomic fluorescence detector (GC-pyro-AFS). A detection limit
      of 6 ng l-1, and reproducibility of 2% was achieved for the CV-AFS method; GC
      pyro-AFS yielded 200 ng l-1 and 5% for detection limit and coefficient of
      variation, respectively. Both procedures were validated with the use of various
      certified reference materials over a wide range of mercury concentrations, and by
      spiking experiments. The validated methods were tested successfully on a wide
      range of commercially available food samples.

PMID- 12195955
TI  - Continuous ultrasound-assisted extraction of hexavalent chromium from soil with
      or without on-line preconcentration prior to photometric monitoring.
AB  - A continuous ultrasound-assisted extractor was coupled to a photometric detector
      in order to obtain a fully automated approach for the determination of CrVI in
      soil. The use of a flow injection (FI) manifold as interface between the
      extractor and the photometric detector allowed the monitoring of CrVI after
      extraction in a continuous manner. The coloured complex formed between 1,5
      diphenylcarbazide (DPC) and CrVI was used as recommended in EPA method 7196A
      because it is one of the most sensitive and selective reactions for CrVI
      determination. A preconcentration minicolumn packed with a strong anion-exchange
      resin was placed between the extractor and the detector, providing a more
      sensitive method. The linear dynamic ranges were 1-10 and 0.25-7.5 mg l-1 for the
      methods without (method A) and with preconcentration (method B), respectively.
      The limits of detection were 4.52 ng for method A and 1.23 ng for method B. Both
      methods were applied to a natural contaminated soil and the results obtained
      agreed well with those obtained by the reference EPA method 3060A. The influence
      of different amounts of CrIII in the samples was also studied and the results
      showed that the proposed methods did not disturb the original species
      distribution.

PMID- 12195956
TI  - Analysis and processing of samples for a carbon-14 monitoring program at a
      radioactive waste storage site.
AB  - A monitoring program was undertaken to determine the levels of airborne
      radioactive 14CO2 in an operating waste management area, and it its vicinity. As
      a part of this program, alkaline microporous pellets, recently developed, were
      used to sample the 14CO2 in air near waste storage structures and near the waste
      management area. These pellets were never fully characterized for their ability
      to capture high levels of 14CO2, and the processing and analysis needed to be
      improved to provide data on recoveries and consistencies, for an eventual method
      validation, with independent calibrations and standards. The sample analysis
      scheme also had to accommodate 14CO2 levels varying from near the natural
      background (250 Bq kg-1 C), to potentially three to four orders of magnitude
      above this value, near the wastes. The porous alkaline solid pellets were used
      for the passive capture of airborne 14CO2 over a period of weeks, to a few
      months. The pellets were processed to release the captured CO2 (14CO2 and 12CO2)
      into a NaOH solution, which was subsequently analyzed by liquid scintillation.
      Processing of the pellets yielded a 14C recovery of 96.0 +/- 4.2% and a lower,
      but consistent total carbon recovery, i.e., 85.9 +/- 2.7 and 86.9 +/- 2.6%, for
      procedural blanks and standards, respectively. The detection limits for the
      pellet sampling and processing was sufficient to reach environmental levels. For
      the higher levels of 14CO2 and for 'spot' sampling, we also used air samples,
      pumped into a NaOH solution to trap the 14CO2. These NaOH solutions were counted
      directly for 14C, also by liquid scintillation. The method limits of this latter
      technique, although much higher than for pellet samples, also achieved the
      performance objective for detecting airborne 14CO2. Both sampling and processing
      techniques, when used together, provided sufficient flexibility to be used for
      low (environmental) levels and high levels, near the wastes.

PMID- 12195957
TI  - Optimisation of microdialysis sampling recovery by varying inner cannula
      geometry.
AB  - In vitro microdialysis recoveries of glucose were evaluated and optimised by
      varying the inner cannula dimensions for a concentric type microdialysis probe.
      The recovery was shown to be significantly dependent on the outer radius of the
      inner cannula (r alpha). Increasing r alpha by 50% while holding all other
      microdialysis variables constant caused a 26% increase in recovery under the
      conditions tested. Mass transport modeling of microdialysis sampling showed that
      the magnitude of the recovery change in response to changes in r alpha may depend
      on other experimental variables such as effective dialysis length, membrane
      dimensions, membrane type and medium composition. These data indicate that
      microdialysis recovery may be substantially improved by optimising the outer
      diameter of the inner cannula. These data also suggest that in order to fully
      characterise and compare data from microdialysis experiments, r alpha should
      become one of the reported variables.

PMID- 12195958
TI  - Sequential injection analysis.

PMID- 12195959
TI  - Argyrins, immunosuppressive cyclic peptides from myxobacteria. I. Production,
      isolation, physico-chemical and biological properties.
AB  - A group of cyclic peptides consisting of 8 amino acid residues, named argyrins A
      to H, were isolated from the culture broth of strains of the myxobacterium
      Archangium gephyra. Argyrin B was found to be a potent inhibitor of T cell
      independent antibody formation by murine B cells and strongly inhibited the two
      way murine mixed lymphocyte reaction. All argyrins had slight antibiotic
      activity, especially against Pseudomonas sp., and inhibited growth of mammalian
      cell cultures. The growth inhibition was often incomplete and varied highly with
      different cell lines.

PMID- 12195960
TI  - Fungal metabolites, asterric acid derivatives inhibit vascular endothelial growth
      factor (VEGF)-induced tube formation of HUVECs.
AB  - In the search for new naturally occurring anti-angiogenic compounds, we found
      that a culture broth of an unidentified fungal strain B90911 exerted inhibitory
      activity on capillary-like tube formation of human umbilical vein endothelial
      cells (HUVEC) in vitro. Four active compounds were isolated by bioassay-guided
      separation and their structures were identified to be sulochrin (1), methyl
      asterric acid (2), and two new asterric acid derivatives, 3-chloroasterric acid
      (3), and 3,5-dichloroasterric acid (4) by spectroscopic analyses. These compounds
      significantly inhibited the VEGF-induced tube formation of HUVEC, suggesting that
      asterric derivatives could be useful for further study as anti-angiogenic agents.

PMID- 12195961
TI  - Atroviridins A-C and neoatroviridins A-D, novel peptaibol antibiotics produced by
      Trichoderma atroviride F80317. I. Taxonomy, fermentation, isolation and
      biological activities.
AB  - Seven new peptaibols, atroviridins A-C composed of 20 residue amino acids and
      neoatroviridins A-D with 18 residues, were isolated from the culture broth of
      fungal strain F80317. The strain F80317 was identified as Trichoderma atroviride
      from its morphological and cultural characteristics. These compounds showed
      antimicrobial activity against Gram-positive bacteria and phytopathogenic fungi,
      and exhibited significant cytotoxicity to human cancer cell lines in vitro.
      Atroviridins showed significant membrane-perturbing activity responsible to their
      antibiotic action.

PMID- 12195962
TI  - Arylomycins A and B, new biaryl-bridged lipopeptide antibiotics produced by
      Streptomyces sp. Tu 6075. I. Taxonomy, fermentation, isolation and biological
      activities.
AB  - New lipopeptide antibiotics, colourless arylomycins A series and yellow
      arylomycins B series were detected in the culture filtrate and mycelium extracts
      of Streptomyces sp. Tu 6075 by HPLC-diode-array and HPLC-electrospray-mass
      spectrometry screening. Arylomycins are a family of lipohexapeptide antibiotics,
      which represent the first examples of biaryl-bridged lipopeptides. They show
      antibiotic activities against Gram-positive bacteria.

PMID- 12195963
TI  - Arylomycins A and B, new biaryl-bridged lipopeptide antibiotics produced by
      Streptomyces sp. Tu 6075. II. Structure elucidation.
AB  - The structures of new lipopeptide antibiotics, arylomycins A and B, were
      elucidated by a combination of ESI-FTICR-mass spectrometry, NMR spectroscopy,
      Edman sequencing, and fatty acid and chiral amino acid analyses. The colourless
      arylomycins A share the peptide sequence of D-N-methylseryl2(D-MeSer2)-D-alanyl3
      glycyl4-N-methyl- 4-hydroxyphenylglycyl5(MeHpg5)-L-alanyl6-tyrosine7 cyclised by
      a [3,3]biaryl bond between MeHpg5 and Tyr7. The yellow arylomycins B differ from
      arylomycins A by nitro substitution of Tyr7. The N-termini of arylomycins A and B
      are acylated with saturated C11-C15 fatty acids (fa1) comprising n, iso, and
      anteiso isomers. Arylomycins A and B represent the first examples of biaryl
      bridged lipopeptides.

PMID- 12195964
TI  - Biosynthesis of the cyclitol moiety of pyralomicin 1a in Nonomuraea spiralis
      MI178-34F18.
AB  - The biosynthetic pathway leading to the cyclitol moiety of pyralomicin 1a (1) in
      Nonomuraea spiralis MI178-34F18 has been studied using a series of 2H-labeled
      potential precursors. The results demonstrate that 2-epi-5-epi-valiolone (7), a
      common precursor for acarbose (4) and validamycin A (5) biosynthesis, is an
      immediate precursor of pyralomicin 1a. 5-epi-Valiolone (8) was also incorporated
      into 1, albeit less efficiently than 7. Other potential intermediates, such as
      valiolone (9), valienone (10), valienol (11), 1-epi-valienol (12), 5-epi-valiolol
      (13), and 1-epi-5-epi-valiolol (14) were not incorporated into pyralomicin 1a. To
      explain this surprising observation, it is proposed that either 2-epi-5-epi
      valiolone (7) is specifically activated (e.g., to its phosphate) and that the
      further transformations take place on activated intermediates (which can not be
      generated directly from their unactivated counterparts), or that the
      transformation of 7 into 1 involves a substrate-channeling mechanism in which
      enzyme-bound intermediates are directly transferred from one enzyme active site
      to the next in a multi-enzyme complex.

PMID- 12195965
TI  - Characterization of Mycotypha metabolites found to be inhibitors of cell adhesion
      molecules.
AB  - Three inhibitors of cell adhesion based on LFA-1/ICAM-1 were isolated from the
      cultured broth of the fungal strain Mycotypha sp. UMF-006. These compounds were
      identified by spectroscopy to be cytochalasin E (1), 5,6-dehydro-7-hydroxy
      derivative of cytochalasin E (2) and delta 6,12-isomer of 2 (3). All these
      components inhibited adhesion of HL-60 cells to CHO-ICAM-1 cells at IC50 values
      of 30 micrograms/ml for 1, 75 micrograms/ml for 2, and 90 micrograms/ml for 3.

PMID- 12195966
TI  - Asterobactin, a new siderophore group antibiotic from Nocardia asteroides.

PMID- 12195967
TI  - Structure elucidation of a new cyclic hexadepsipeptide from Beauveria felina.

PMID- 12195969
TI  - Inhibitory activity of dome formation in LLC-PK1 cells is a selective index of
      aminoglycoside nephrotoxicity.

PMID- 12195968
TI  - A method to assay glyoxylate cycle inhibitors for antifungals.

PMID- 12195970
TI  - UK-2A, B, C and D, novel antifungal antibiotics from Streptomyces sp. 517-02 VI
      (2). Structure-activity relationships of UK-2A.

PMID- 12195972
TI  - Integrated model for estimating phosphor signal and noise transfer
      characteristics on medical images: application to CdPO3Cl:Mn phosphor screens.
AB  - An integrated model describing the signal and noise transfer characteristics of
      the objective image quality and information content in phosphor-produced images
      is presented. In the context of this model, important imaging parameters, namely
      optical gain, modulation transfer function, noise transfer function, detective
      quantum efficiency and information capacity were experimentally evaluated using
      seven laboratory-prepared CdPO3Cl:Mn test phosphor screens of varying coating
      thickness. This phosphor has been previously shown to exhibit high spectral
      compatibility properties with the films and optical sensors used in digital
      imaging systems. Experiments were performed using 50-120 kVp X-rays produced by a
      medical X-ray unit. Results showed that, for thick screens, optical gain attained
      peak values close to 200 optical photons per incident X-ray at 50 kVp. The noise
      transfer function was higher than the modulation transfer function. For the thin
      screen of 21 mg cm-2, the modulation transfer function was 0.25 at 100 line pairs
      mm-1, and the corresponding noise transfer function was 0.4. The detection
      quantum efficiency peak value was 0.22 at 50 kVp. These values are within
      acceptable performance limits, and, given the phosphor material's high spectral
      compatibility and medium temporal response, CdPO3Cl:Mn could be considered for
      use in X-ray detectors of static radiography imaging.

PMID- 12195971
TI  - Detection of pulsatile blood flow cycle in frog microvessels by image
      velocimetry.
AB  - The detection of pulsatile blood flow velocity through one section of a curved
      branching frog mesenteric microvessel during a flow cycle, by analysis of a
      sequence of videomicroscopic images recorded at a frame rate 25 frames s-1, is
      presented. From these data, 64 sequential digitized frames of 128 x 128 pixels
      and 256 grey level were selected. By processing sequential pairs of frames by
      image velocimetry, the corresponding displacement vector was calculated. Dividing
      this by the frame rate gave the vector velocity. The same procedure was repeated
      for all frames, and the corresponding maximum (0.36-0.38 mm s-1), minimum (0.0
      0.025 mm s-1) and other velocity values were obtained and plotted. The
      preliminary data analysis showed that the separation between two velocity maxima
      was about 20 video frames, which corresponded to one cardiac cycle of time
      interval 0.8 s.

PMID- 12195973
TI  - Effects of noise on transient-evoked oto-acoustic emission pass/fail criteria.
AB  - This study investigated the effects of noise on typical transient-evoked oto
      acoustic emission (TEOAE) pass/fail criteria. Different levels of synthesised
      noise were added to one TEOAE signal, to determine the relationship between the
      signal-to-noise ratio (SNR) and typical TEOAE parameters: reproducibility, TEOAE
      level and corrected TEOAE level. Results showed that, with the same TEOAE signal,
      if the SNR decreased from 19 dB to -7 dB, the means of estimated reproducibility
      decreased from 97% to 7%, and the means of estimated TEOAE levels were doubled.
      Only the means of estimated corrected TEOAE levels were relatively insensitive to
      SNR. The standard deviations of all TEOAE parameter estimators increased with
      decreasing SNR. With these results, this study proposed that each typical TEOAE
      parameter alone should not be taken as the absolute pass/fail criterion. A
      combination of the corrected TEOAE level and the reproducibility would be better.

PMID- 12195974
TI  - Standing-up exerciser based on functional electrical stimulation and body weight
      relief.
AB  - The goal of the present work was to develop and test an innovative system for the
      training of paraplegic patients when they are standing up. The system consisted
      of a computer-controlled stimulator, surface electrodes for quadricep muscle
      stimulation, two knee angle sensors, a digital proportional-integrative
      derivative (PID) controller and a mechanical device to support, partially, the
      body weight (weight reliever (WR)). A biomechanical model of the combined WR and
      patient was developed to find an optimum reference trajectory for the PID
      controller. The system was tested on three paraplegic patients and was shown to
      be reliable and safe. One patient completed a 30-session training period.
      Initially he was able to stand up only with 62% body weight relief, whereas,
      after the training period, he performed a series of 30 standing-up/sitting-down
      cycles with 45% body weight relief. The closed-loop controller was able to keep
      the patient standing upright with minimum stimulation current, to compensate
      automatically for muscle fatigue and to smooth the sitting-down movement. The
      limitations of the controller in connection with a highly non-linear system are
      considered.

PMID- 12195975
TI  - Using three-dimensional difference maps to assess changes in scoliotic
      deformities.
AB  - The three-dimensional nature of scoliosis, coupled with changes due to natural
      history or treatment, is often difficult to quantify and visualise. A difference
      map was developed to compare the sequential surface topography of subjects over
      their treatment period. Three-dimensional surface maps representing patients'
      trunk surfaces were captured with a laser scanner. Patient surface maps from two
      clinic visits were matched using a manual best-fit technique that accounted for
      growth and positioning. The surfaces were subtracted, generating a colour-coded
      three-dimensional difference map displaying the surface changes. The difference
      maps were compared with known clinical measures, indicating good agreement (78%
      specific) with the clinical parameters in detecting change. Full agreement or
      agreement with the clinical parameters occurred in the surgical, brace and no
      treatment groups: 76%, 80% and 85%, respectively. A difference index (average of
      the absolute value of differences on a point-by-point basis) was calculated from
      the difference map, enabling quantification of change. The difference index, with
      zero being a perfect match, averaged 5 +/- 1 for repeated measures 7 +/- 2 for
      subjects deemed to have no change, 9 +/- 2 for subjects with slight change, and
      14 +/- 2 for subjects with significant change. The difference map showed the
      extent and location of changes and is a useful tool for assessing surface
      topography changes.

PMID- 12195976
TI  - Biomechanical evaluation of Cheneau-Toulouse-Munster brace in the treatment of
      scoliosis using optimisation approach and finite element method.
AB  - The aim of the study was to investigate the mechanisms of the Cheneau-Toulouse
      Munster (CTM) brace in the correction of scoliotic curves, at night in the supine
      position. Magnetic resonance imaging (MRI) and Computer tomography (CT)
      acquisitions were performed in vivo on eight girls having an idiopathic scoliosis
      and being treated for the first time using a personalized CTM brace. Personalized
      3D finite element models of the spine were developed for each patient, and an
      optimisation approach was used to quantify the forces generated by each brace on
      each scoliotic spine. A sensitivity study was undertaken to test the assumptions
      about intervertebral behaviour and load transmission from the brace to the spine.
      The computed CTM brace forces were 9-216N in the coronal plane and 2-72N in the
      sagittal plane. Personalized spinal stiffness properties should be included in
      spine models because, in this study, partial correction resulted from the
      application of higher estimated forces than for total correction. Partially
      reduced spines should be stiffer than totally reduced spines. The sensitivity
      study showed that the computed brace forces were proportional to the
      intervertebral Young's modulus and should be analysed as estimated data. Better
      knowledge of brace forces should be helpful in brace design to achieve the best
      correction of first scoliotic deformities.

PMID- 12195977
TI  - Biomechanical analysis of fatigue-related foot injury mechanisms in athletes and
      recruits during intensive marching.
AB  - An integrative analysis, comprising radiographic imaging of the foot, plantar
      pressure measurements, surface electromyography (EMG) and finite element (FE)
      modelling of the three-dimensional (3D) foot structure, was used to determine the
      effects of muscular fatigue induced by intensive athletic or military marching on
      the structural stability of the foot and on its internal stress state during the
      stance phase. The medial/lateral (M/L) tendency towards instability of the foot
      structure during marching in fatigue conditions was experimentally characterised
      by measuring the M/L deviations of the foot-ground centre of pressure (COP) and
      correlating these data with fatigue of specific lower-limb muscles, as
      demonstrated by the EMG spectra. The results demonstrated accelerated fatigue of
      the peroneus longus muscle in marching conditions (treadmill march of 2 km
      completed by four subjects at an approximately constant velocity of 8 km h-1).
      Severe fatigue of the peroneus longus is apparently the dominant cause of lack of
      foot stability, which was manifested by abnormal lateral deviations of the COP
      during the stance phase. Under these conditions, ankle sprain injuries are likely
      to occur. The EMG analysis further revealed substantial fatigue of the pre-tibial
      and triceps surae muscles during intensive marching (averaged decreases of 36%
      and 40% in the median frequency of their EMG signal spectra, respectively).
      Incorporation of this information into the 3D FE model of the foot resulted in a
      substantial rise in the levels of calcaneal and metatarsal stress concentrations,
      by 50% and 36%, respectively. This may point to the mechanism by which stress
      fractures develop and provide the biomechanical tools for future clinical
      investigations.

PMID- 12195978
TI  - Computational simulations of stress shielding and bone resorption around existing
      and computer-designed orthopaedic screws.
AB  - Failure of an orthopaedic fixation due to stress shielding and consequent screw
      loosening is a major concern among surgeons: the loosened screws could not only
      interfere with the healing process but also endanger adjacent anatomical
      structures. In this study, the effect of the screw's engineering design
      (dimensions, profile shape and material properties) on the load sharing with
      adjacent bone and consequent bone resorption was tested, using a set of two
      dimensional computational (finite element) models. An algorithm simulating local
      bone adaptation to strain energy density (SED) mechanical stimuli was developed
      and used to evaluate the biomechanical performances of different commercial
      screws. Two new designs, a 'graded-stiffness' composite screw, with a reduced
      stiffness titanium core and outer polymeric threads, and an active-compression
      hollow screw that generates compressive stresses on the surrounding bone, were
      also evaluated. A dimensionless set of stress transfer parameters (STPs) were
      utilised for ranking the performances of the different screws according to the
      expected screw-bone load sharing and its evolution with adaptation of the
      surrounding tissue. The results indicated that commercial wide (6 mm thread
      diameter) trapezoidal and rectangular screw profiles have superior biomechanical
      compatibility with bone (i.e. predicted to be stable after 2 years). The graded
      stiffness and active-compression screws provided the best biomechanical
      performances: bone loading around them was predicted to decrease by no more than
      15% after 3 years, compared with a decrease of 55-70% in bone loading around
      commercially available screws. Computer simulations of bone adaptation around
      orthopaedic screws are demonstrated to be effective means for objective and
      quantitative evaluation of the biomechanical aspects of implant-tissue
      compatibility.

PMID- 12195979
TI  - In vivo impedance measurements on nerves and surrounding skeletal muscles in rats
      and human body.
AB  - The aim of the work was to use impedance measurements to find the location of
      nerves under the human skin. In vivo impedance measurements were performed on
      exposed nervous and muscular tissues of rats. Similarly, the impedance
      measurements were also performed on the skin of six men, over the median nerve at
      the wrist, as well as 4-5 mm away from this location. Results obtained with rats
      have shown that the relative permittivity and conductivity of nerves are larger
      (by almost two orders of magnitude) than those observed for the muscular tissues
      surrounding the nerve. The results obtained on human skin in the frequency range
      of 20-200 kHz, when the electrodes were placed over the nerve, show lower
      resistance and higher capacitance than in the other areas measured. These
      preliminary results indicate that it may be possible to use impedance
      measurements to find the location of exposed nerves and also nerves under the
      skin.

PMID- 12195980
TI  - Visualisation method of spatial interictal discharges in temporal epilepsy
      patients using magneto-encephalogram.
AB  - The aim of the study was to develop a method for investigating how interictal
      epileptic discharges in temporal epilepsy patients are activated spatially. The
      activity was measured using magneto-encephalography (MEG). The MEG data were used
      to produce a current-arrow map that reflected the topographic distribution of the
      electrical current for each peak epileptic waveform. A large current distribution
      was obtained that appeared to be contained in the limbic structure, in each
      temporal lobe. The large current orientation indicated two opposite directions.
      Furthermore, the decrease in the maximum strength of the current-arrow, depending
      on the medication (e.g. the decrease from 11 to 6 pT m-1 in the left temporal
      lobe (contralateral stimuli)), suggested that the discharge distributions could
      be used to verify the efficacy of medication. Thus the topographical
      visualisation method could be a new strategy for diagnosis in temporal epilepsy
      patients.

PMID- 12195981
TI  - Investigation into the origin of the noise of surface electrodes.
AB  - In the recording of biomedical signals, a significant noise component is
      introduced by the electrode. The magnitude of this noise is considerably higher
      than the equivalent thermal noise from the electrode impedance. As the noise in
      surface electrodes limits the resolution of biopotential recordings, it is
      important to understand its origin. It was found that the noise mainly originates
      in the electrolyte-skin interface and that it is highly dependent on the
      electrode gel used and the skin properties of the test subject. Depending on skin
      treatment, magnitudes between 1 and 20 microVrms were measured among subjects.
      When the metal-electrolyte interface was allowed time to stabilise, electrodes of
      different metals measured face to face all showed a negligibly small noise
      magnitude (< 1 microVrms). In pre-gelled electrodes, where the metal-electrolyte
      interface has stabilised, no difference in noise properties was found between Ag
      AgCl electrodes and other metals when measured on the skin. In subjects at rest,
      the contribution of EMG signals to the total noise level was shown to be
      negligibly small compared with the noise contribution of the electrolyte-skin
      interface. The magnitude of the noise of electrodes appeared to be inversely
      proportional to the square root of the area of the electrode on the skin.

PMID- 12195982
TI  - Classifying coronary dysfunction using neural networks through cardiovascular
      auscultation.
AB  - The paper applies artificial neural networks (ANNs) to the analysis of heart
      sound abnormalities through auscultation. Audio auscultation samples of 16
      different coronary abnormalities were collected. Data pre-processing included
      down-sampling of the auscultated data and use of the fast Fourier transform (FFT)
      and the Levinson-Durbin autoregression algorithms for feature extraction and
      efficient data encoding. These data were used in the training of a multi-layer
      perceptron (MLP) and radial basis function (RBF) neural network to develop a
      classification mechanism capable of distinguishing between different heart sound
      abnormalities. The MLP and RBF networks attained classification accuracies of 84%
      and 88%, respectively. The application of ANNs to the analysis of respiratory
      auscultation and consequently the development of a combined cardio-respiratory
      analysis system using auscultated data could lead to faster and more efficient
      treatment.

PMID- 12195983
TI  - Simulation study of the Hemopump as a cardiac assist device.
AB  - A dynamic model was developed for a Hemopump that withdraws blood from the left
      ventricle and discharges it to the aorta through a miniature axial-flow pump.
      Incorporation of the Hemopump model in a previously established model for the
      canine circulatory system enabled the effects of the Hemopump on various
      haemodynamic variables of the circulatory system to be studied, and the benefit
      of the Hemopump to the failing heart was investigated. In addition, the influence
      of the physiological status of the right ventricle on the Hemopump performances
      was examined, and the synchronous and non-synchronous operations of the Hemopump
      were compared. Results verified that the Hemopump assists the failing heart by
      increasing the oxygen supply, while reducing the oxygen consumption of the heart
      through a reduction in the workload of the left ventricle. These beneficial
      effects were enhanced when the pump's rotation speed was increased. When pump
      speed was increased from 17,000 to 23,000 revolutions min-1, the oxygen supply
      increased 101%, and the oxygen consumption decreased 60%. However, when the pump
      rotation speed was too high, the inflow to the pump could be impaired and the
      pump performance could be negatively affected. Predications from the model were
      in good agreement with the results previously obtained in animal experiments and
      in vitro measurements.

PMID- 12195984
TI  - Electrical phosphenes: on the influence of conductivity inhomogeneities and small
      scale structures of the orbita on the current density threshold of excitation.
AB  - Electrical and magnetic phosphenes, perceptions of light as a result of non
      adequate stimulation of the eye by electrical current or magnetic induction,
      respectively, are one of the cornerstones to justify limit values for extreme low
      frequency fields specified by statutory regulations. However, the mechanism and
      place of action, as well as the excitation threshold, remain unknown until now.
      We suggest that the origin of phosphene excitation is the synaptic layer of the
      eye. The current density threshold value for electrical phosphene excitation was
      numerically quantified for this area on the basis of a detailed geometrical model
      in original submillimetre resolution and specifically measured conductivities in
      the LF range. The threshold values found were 1.8 A m-2 at 60 Hz and 0.3 A m-2 at
      25 Hz. These values are comparable with values of other excitable tissues. It has
      been shown that the current density threshold for phosphene generation depends on
      small-scale structures not taken into account by previous models.

PMID- 12195985
TI  - Effects of high-rate electrical stimulation upon firing in modelled and real
      neurons.
AB  - Many medical devices use high-rate, low-amplitude currents to affect neural
      function. This study examined the effect of stimulation rate upon action
      potential threshold and sustained firing rate for two model neurons, the rabbit
      myelinated fibre and the unmyelinated leech touch sensory cell. These model
      neurons were constructed with the NEURON simulator from electrophysiological
      data. Alternating-phase current pulses (0-1250 Hz), of fixed phase duration (0.2
      ms), were used to stimulate the neurons, and propagation success or failure was
      measured. One effect of the high pulse rates was to cause a net depolarisation,
      and this was verified by the relief of action potential conduction block by 500
      Hz extracellular stimulation in leech neurons. The models also predicted that the
      neurons would maintain maximum sustained firing at a number of different
      stimulation rates. For example, at twice threshold, the myelinated model followed
      the stimulus up to 500 Hz stimulation, half the stimulus rate up to 850 Hz
      stimulation, and it did not fire at 1250 Hz stimulation. By contrast, the
      unmyelinated neuron model had a lower maximum firing rate of 190 Hz, and this
      rate was obtained at a number of stimulation rates, up to 1250 Hz. The myelinated
      model also predicted sustained firing with 1240 Hz stimulation at threshold
      current, but no firing when the current level was doubled. Most of these effects
      are explained by the interaction of stimulus pulses with the cell's refractory
      period.

PMID- 12195986
TI  - Mercury in wild mushrooms and underlying soil substrate from the great lakes land
      in Poland.
AB  - Fifteen species of wild mushrooms and underlying soil samples collected in a
      virgin landscape of Augustowska Forest in northeastern Poland in 1997-98 were
      analyzed for total mercury to evaluate the status of contamination and usefulness
      of higher mushrooms as possible bioindicators of mercury pollution. Among the 15
      species analyzed, Pinewood King Bolete, Scaly Tooth and King Bolete showed
      relatively high bioconcentration factors (BCF: dry-weight normalized
      concentrations of mercury in mushrooms relative to concentrations in soil) for
      mercury, which varied between 69 and 110. These three species were also
      characterized by great concentrations of total mercury in caps (between 2,000 +/-
      800 and 2,300 +/- 1,100 ng g-1 dry wt) and stalks (between 850 +/- 390 and 1,000
      +/- 500 ng g-1 dry wt.). Species such as Red-hot Milk Cap, Poison Pax and Common
      Chantherelle had mercury BCFs of less than 1, while Gipsy Bolete, Orange Birch
      Bolete, Brown Scaber Stalk, Variegated Bolete, Sandy Knight-cap and Yellow
      cracking Bolete were weak or moderate mercury accumulators with BCFs between 1
      and 40. Concentrations of mercury in mushrooms were greater than the tolerance
      limits suggested for mercury in plant foods.

PMID- 12195987
TI  - Solid-phase microextraction coupled to gas chromatography-mass spectrometry for
      the study of soil adsorption coefficients of organophosphorus pesticides.
AB  - A solid-phase microextraction-gas chromatography-mass spectrometry (SPME-GC-MS)
      method for the simultaneous determination of the organophosphorus pesticides
      (OPPs), phorate, diazinon, methyl-parathion, fenitrothion, malathion, fenthion,
      ethyl-parathion and methidathion, has been developed to study their soil/water
      distribution. The method was used in conjunction with a conventional 'batch
      equilibrium method' to assess the soil adsorption coefficients (Koc) of the
      target compounds in different soil samples with known organic carbon content.
      Contrary to traditional techniques, the present method is fast, solvent-free and
      highly sensitive, thus permitting the assessment of the Koc values of the target
      compounds even at low soil concentration levels, close to those encountered in
      real field contamination, where the Freudlich adsorption isotherms can be
      considered to be linear. The estimated Koc values were found to be in good
      agreement with those reported in the literature.

PMID- 12195988
TI  - Evaluation of interactive toxicity of chlorophenols in water and soil using lux
      marked biosensors.
AB  - An assessment of the toxicity of three chlorophenol compounds (2,4-dichlorophenol
      (2,4-DCP), 2,4,6-trichlorophenol (2,4,6-TCP) and pentachlorophenol (PCP)),
      individually and in combinations, was made in deionised water, soil extracts and
      soils using the lux-marked microbial biosensors: Escherichia coli HB101 pUCD607
      and Pseudomonas fluorescens 10586r pUCD607. These biosensors responded to the
      bioavailable fraction of pollutants enabling a rapid and ecologically relevant
      toxicity test. Toxicity interaction responses of pollutant mixtures were
      predicted after individual compounds were assessed. Synergistic interactions were
      observed in the response of P. fluorescens to all combinations of chlorophenols
      tested, while the toxicity response of E. coli varied with the matrices tested.
      Soil characteristics influenced the toxicity response when compared with aqueous
      solutions. These results highlight the significance of interactive factors and
      physicochemical parameters when evaluating toxicity. To develop an understanding
      of pollution derived hazard assessment in soils we need to integrate a wide
      spectrum of parameters.

PMID- 12195989
TI  - Strategically designed sample composition for fastest screening of
      polychlorinated biphenyl congeners in water samples.
AB  - A new strategy for preparing composite samples of special interest and
      applicability in environmental screening studies is presented. The use of
      supersaturated experimental design matrices to conduct the sample composition of
      water sample specimens in screening studies is demonstrated. In contrast to well
      known conventional sample composition, this strategic approach provides
      analytical objects allowing the accurate prediction of analyte concentration
      levels in the original individual sample specimens while fixing the number of
      experiments to be carried out down to the very number of sample specimens. This
      will be of special importance when dealing with analytes that require
      complicated, labour intensive and expensive analytical processes. To reach this
      goal, two main conditions must be fulfilled. The first one is the sparsity effect
      (Pareto principle) which holds for the specimens in the sampling campaign. This
      means that the number of really anomalous or contaminated specimens, as compared
      to the total number of specimens to be analysed, is low. In environmental
      screening studies, frequently this situation can be reasonably assumed. The
      second condition is to have an effective manner to develop and solve the
      experimental designs required to build-up the composite samples. The challenging
      problem of screening PCBs in water samples has been tackled to show the
      usefulness of this strategic approach by combining chemometrically assisted
      sample composition and rapid analysis using solid-phase microextraction of the
      composite samples.

PMID- 12195990
TI  - Occurrence and behaviour of organophosphorus insecticides in the River Wuchuan,
      southeast China.
AB  - Organophosphorus (OP) insecticides are used worldwide, yet their persistence in
      the environment is not well understood. This paper summarises recent research on
      17 OP insecticides in the River Wuchuan, an important catchment in China, by
      determining their concentrations in water, soil, sediment and plants by gas
      chromatography with flame photometric detection (GC-FPD). The concentrations of
      the total OP insecticides ranged from 92.77 to 229 ng l-1 in river water, 1.61 to
      9.93 ng g-1 dry weight in soil, 1.24 to 7.56 ng g-1 dry weight in sediment and
      75.28 to 326 ng g-1 dry weight in plants. There was a relatively high abundance
      of methamidophos, dichlorvos, malathion, omethoate and dimethoate in all water,
      soil, sediment and plant samples. On average, these five compounds collectively
      accounted for 64%, 71%, 71% and 54% of the total OP insecticide concentration in
      water, soil, sediment and plants, respectively, which was similar to the
      composition of OP insecticides in application formulations used in our study area
      and in China as a whole. The results therefore reflect the application pattern to
      some extent, and suggest that the sources of the OP insecticides are mainly from
      current usage. When compared with other areas, the levels of OP insecticides in
      the River Wuchuan were moderate. The animal and human risks from exposure to OP
      insecticides in water and plants were evaluated against relevant threshold
      values. The results therefore provide important information on the current
      contamination status of a key agricultural watershed in China, and point to the
      need for urgent action to control the use of some excessively applied and
      potentially persistent agrochemicals, such as methamidophos, omethoate and
      dimethoate.

PMID- 12195991
TI  - Copper fractionation with dissolved organic matter in natural waters and
      wastewater--a mixed micelle mediated methodology (cloud point extraction)
      employing flame atomic absorption spectrometry.
AB  - A cloud point extraction-preconcentration methodology for the speciation analysis
      of free and organically complexed metal species in natural waters is presented.
      The method is based on the neutralization of the electrostatic charge of the
      humate-metal complexes with a positively charged surfactant in a high ionic
      strength solution environment. The resulting complexes are conveniently
      solubilized in the micelles of a non-ionic surfactant medium and are thus
      separated from the bulk aqueous phase. Free metal species are also determined by
      complexation with a conventional chelating agent under mild conditions. The
      overall procedure is easy, rapid and allows for a high sample throughput in terms
      of massive analysis of many samples in the same time period. The method offers
      substantially low detection limits of 8.5 and 0.9 micrograms l-1 for bound and
      labile species respectively, with a calibration curve rectilinear in the wide
      range 40-150 micrograms l-1 for the humate associated and 4-40 micrograms l-1 for
      the free metal species. The method is free from interferences yielding recoveries
      in the range 97-102% for various samples of different matrixes.

PMID- 12195992
TI  - Destruction of fecal bacteria in wastewater by three photosensitizers.
AB  - Agriculture in Tunisia faces acute problems of water quality and quantity caused
      by limited conventional water resources. One possibility to cope with low water
      resources is to purify wastewater for reuse. Among different methods for the
      disinfection of wastewater, the inactivation of fecal coliforms using a
      combination of a photosensitiser (Rose Bengal, Methylene Blue, cationic
      porphyrin) with sunlight was determined on a small scale. In parallel the
      sensitizer photobleaching was also followed under the same conditions. The
      results described in this paper show that the meso-substituted cationic porphyrin
      is more efficient and more photostable than Methylene Blue and Rose Bengal in
      wastewater. A lower cationic porphyrin concentration, 1 microM, resulted in very
      little cell death. Higher concentrations, 5 microM or 10 microM, produced more
      cell death. Nevertheless there was a small difference between concentrations 5
      and 10 microM. By increasing the duration of irradiation we can improve the log
      reduction in bacteria and compensate for a low concentration of sensitizer or for
      a less efficient type of sensitizer. The same log reduction in fecal bacteria was
      obtained with 5 and 10 microM of cationic porphyrin during the fourth hour of
      treatment.

PMID- 12195993
TI  - Application of cryofocusing hydride generation and atomic fluorescence detection
      for dissolved mercury species determination in natural water samples.
AB  - The concentration levels of mercury (Hg) species in natural water samples are
      usually low. Consequently, accurate analysis with low detection limits is still a
      major problem. In this work, a method was applied for the simultaneous direct
      determination of dissolved mercury species in water samples by on-line hydride
      generation (HG), cryogenic trapping (CT), gas chromatography (GC) and detection
      by atomic fluorescence spectrometry (AFS). The suitability of the method for real
      samples with different organic matter and chloride contents was evaluated by
      recovery experiments in synthetic and natural spiked water samples. The HG method
      was compared with other current available methods for mercury analysis with
      respect to the different fraction of mercury analysed, i.e. 'reactive',
      'reducible' or total. HG derivatization and SnCl2 reduction (with and without
      previous oxidation with BrCl) were applied to synthetic and natural (spiked and
      non-spiked) water samples. The influence of chloride and dissolved organic matter
      concentrations was studied. The results suggest that the HG procedure is suitable
      for the simultaneous determination of Hg2+ and MeHg+ in surface water samples.
      Inorganic mercury analysed by HG (i.e. reducible) is close to the total inorganic
      mercury.

PMID- 12195994
TI  - On-line solid phase extraction with polyurethane foam: trace level
      spectrophotometric determination of iron in natural waters and biological
      materials.
AB  - This paper reports the development of a simple and accurate on-line procedure for
      preconcentration and determination of dissolved iron in waters and biological
      materials using unloaded polyether-type polyurethane foam as solid extractor. In
      the developed flow injection system, the analyte was preconcentrated from acidic
      aqueous medium as iron-thiocyanate complex with post-elution with ascorbic acid
      solution and spectrophotometric measurement with 1,10-phenanthroline as
      colorimetric reagent. In order to improve the performance of the system several
      chemical and flow variables were investigated as well as the effect caused by the
      presence of possible interferents. The method was validated by the analysis of
      two certified reference materials. Application of the methodology was carried out
      by the determination of dissolved iron content in eight natural water samples
      with different characteristics. The results were compared with those obtained by
      electrothermal atomic absorption spectrometry (ETAAS) and no statistical
      difference was observed. The detection limit was 0.75 microgram l-1 and the RSD
      was 1.2% for 2 min preconcentration time. At this condition, a productivity of 20
      samples h-1 was achieved. Increasing the preconcentration time up to 3 min, a
      detection limit of 0.45 microgram l-1, an RSD of 1.5% and an analytical
      throughput of 15 h-1 were verified.

PMID- 12195995
TI  - The effect of thermodynamic data on computer model predictions of uranium
      speciation in natural water systems.
AB  - Computer models have found widespread application in order to help elucidate and
      predict changes in environmental systems. One such application is the prediction
      of trace metal speciation in aqueous systems. This is achieved by solving a set
      of non-linear equations involving equilibrium constants for all the components in
      the system, within mass and charge balance constraints. In this study a
      comparison of the predicted uranium speciation from two computer programs, WHAM
      and PHREEQCI, is used to illustrate the effect variations in thermodynamic data
      can have on the models produced. Using the original thermodynamic data provided
      with the models, WHAM predicted the UO2(2+) ion as the major species (84%) while
      PHREEQCI predicted UO2(HPO4)2(2-) as the major species (86%). Substituting
      uranium data from the Nuclear Energy Agency Thermochemical Database project (NEA
      TDB) into both programs produced similar results from each program, with UO2F+
      predicted to dominate (68%) in a groundwater sample. Natural water samples often
      contain humic substances. The possible interaction of such substances with
      uranium was also modelled. The WHAM program includes a discreet site
      electrostatic humic substance model, however in order to use the PHREEQCI program
      to model humic substance interactions, a 'model fulvic acid' dataset was added to
      the program. These models predicted 85 to 98% uranium-humic substance species at
      neutral pH. This indicates that humic substances do need to be taken into account
      when modelling uranium speciation in natural water samples.

PMID- 12195997
TI  - Evaluation of performance of time-saving extraction devices in the BCR three-step
      sequential extraction procedure.
AB  - Two alternative extraction methods--a routine ultrasonic bath and a microwave
      oven--were developed and optimized for their eventual exploitation in the three
      stage sequential extraction procedure proposed by the European Standards,
      Measurements and Testing (S, M & T) Programme, formerly Bureau Communitaire de
      Reference (BCR), for the operationally defined speciation of Cd, Cr, Cu, Ni and
      Zn. The conventional BCR three-stage sequential extraction procedure was modified
      at each stage, applying ultrasonic or microwave devices in order to shorten the
      required 16 h of shaking in all three steps. The experimental tests and the
      optimization of the operating parameters were carried out on a highly homogenized
      estuarine sediment reference material (RM S7) prepared by the Joint Research
      Centre (JRC) of ISPRA. Extractable metal contents were measured by inductively
      coupled plasma-mass spectrometry (ICP-MS) and the results obtained in each
      fraction by all three methods were statistically compared for all the studied
      elements. The conventional and newly developed alternative extraction methods
      were finally compared by the analysis of BCR 601, which is certified for the
      three-step BCR sequential extraction procedure. According to the statistical
      evaluation of the results, the proposed accelerated sequential extraction methods
      are valid alternatives to conventional shaking, with much shorter extraction
      times.

PMID- 12195996
TI  - Evolution of water chemistry in natural acidic environments in Yangmingshan,
      Taiwan.
AB  - In Yangmingshan National Park, located in the northern part of the Taiwan Island,
      there is a very rare area where fish (Channa asiatica) live in spite of acid
      environments. The origin of the acid in local acid ponds and rivers and the
      evolution of the water chemistry are discussed on the basis of sulfur stable
      isotope ratios and chemical equilibria. One of the sources of the acid is
      sulfuric acid, which is derived from the oxidation of hydrogen sulfide in
      volcanic gas gushing out from fumaroles around the area and from acid deposition
      supplied from Taipei City. It is also derived from the oxidation of pyrite: the
      sulfur stable isotope ratios of delta 34S of +1@1000 to +4@1000 (relative to CDT)
      of sulfate in acid pond waters (pH 3-4) could be related to those of hydrogen
      sulfide in volcanic gas, pyrite in local pond sediments and soils, and sulfate in
      rain water. One acid source is sulfuric and hydrochloric acids arising in springs
      from geothermal activity: the delta 34S values were characterised by +13@1000 to
      +17@1000 sulfate-S, which was provided by a disproportionation reaction of sulfur
      dioxide in the depths. Another acid source could be the oxidation of iron(II).
      Under acidic conditions, the water-rock reaction gives rise to high
      concentrations of aluminium and iron. While flowing down surface streams,
      iron(II) is oxidised to iron(III) and then hydrolysed to cause further
      acidification under oxic conditions. The concentrations of iron and aluminium are
      controlled by redox and dissolution equilibria.

PMID- 12195998
TI  - Seasonal effects on the air-water carbon dioxide exchange in the Hooghly estuary,
      NE coast of Bay of Bengal, India.
AB  - Monthly variation of CO2 fugacity (fCO2) in surface water and related atmospheric
      exchanges were measured in the Hooghly estuary which is one of the most important
      estuaries, since it is fed by one of the world's largest rivers, the Ganges with
      a flow of 15,646 m3 s-1 (1.6% of the world's combined river flow). Carbon dioxide
      fluxes averaged over the entire estuary are in the range of -2.78 to 84.4 mmol m
      2 d-1. This estuary acts as a sink for CO2 during monsoon months and seasonal
      variation of its flux is controlled by dilution of seawater by river water. Since
      the solubility of CO2 and the disassociation of carbonic acid in estuarine water
      are controlled by temperature and salinity, the observed variations of CO2 fluxes
      are compared with those predicted from seasonal changes in temperature, salinity
      and the ratio of gross primary production to community respiration using
      empirical equations with an explained variability of 55%.

PMID- 12195999
TI  - The potential for anaerobic mineralisation of hydrocarbon constituents of oily
      drill cuttings from the North Sea seabed.
AB  - The potential for natural attenuation of hydrocarbons in oily drill cuttings from
      the seabed beneath a North Sea oil platform was investigated. The study focused
      on the anaerobic degradation of n-hexadecane, n-octacosane and naphthalene using
      additions of 14C-labelled analogues to drill cuttings samples and was conducted
      under realistic seabed conditions (except pressure) over an 11-month period. No
      mineralisation of naphthalene was detected over this time period and
      mineralisation of octacosane represented only 0.5-1.5% of the added label. In
      contrast, mineralisation of hexadecane was 10-49% after 11 months of incubation.
      Selective inhibition of key functional bacterial groups revealed the key role of
      both sulfate reduction and methanogenesis in the degradation process. This study
      demonstrates the potential for natural attenuation of at least some hydrocarbon
      constituents of oily drill cuttings under realistic environmental conditions and
      highlights the involvement of a wide functional consortium in the natural
      attenuation process.

PMID- 12196000
TI  - Measurements of semivolatile and particulate polycyclic aromatic hydrocarbons in
      a bus station and an urban tunnel in Salvador, Brazil.
AB  - Motor vehicles constitute a significant source of polycyclic aromatic hydrocarbon
      (PAH) emissions to the atmosphere. Particle-phase priority pollutant PAH
      concentrations and total suspended particle mass (TSP) were measured in the Lapa
      bus station and the Americo Simas Tunnel, located in the city of Salvador,
      Brazil. Separate samples were collected at the bus station at different times of
      the day, including rush- and non-rush-hour periods. The highest concentrations
      for nearly all 16 priority PAHs measured at the bus station were observed at
      18:30 h, with chrysene showing the highest mean value (26.6 ng m-3). The highest
      average PAH concentrations measured in the tunnel were observed for pyrene (79.4
      +/- 11.5 ng m-3) followed by fluoranthene (39.0 +/- 5.2 ng m-3) and chrysene
      (28.0 +/- 4.17 ng m-3). TSP levels reached 423 micrograms m-3 in the bus station,
      and values as high as 2 mg m-3 in the tunnel. The measured Salvador tunnel PAH
      profiles are very similar to the Salvador bus station profiles, and are similar
      to PAH profiles reported for the Kojouike Tunnel, located in Kurashiki City,
      Japan, and the Caldecott Tunnel, located in Berkeley, California.

PMID- 12196001
TI  - Relationship between environmental exposure to toluene, xylene and ethylbenzene
      and the expired breath concentrations for gasoline service workers.
AB  - This study evaluated the relationship between the breath concentrations of, and
      personal exposure to, toluene, xylene and ethylbenzene of thirty workers from ten
      gasoline stations. Personal exposure air samples and workplace samples were
      collected simultaneously. Each subject provided a sample of exhaled breath after
      his or her personal exposure air was sampled. Twenty-five personal air, 17
      workplace and 30 breath samples were collected in this study. Results indicated
      that breath concentrations of toluene and xylene were significantly correlated
      with personal monitoring concentrations. Furthermore, multiple regression
      analysis showed that exhaled toluene levels were highly influenced by personal
      toluene concentrations and the amount of personal gasoline sold (r2 = 0.762),
      while exhaled xylene levels depended on wind speed and personal xylene exposure
      concentrations (r2 = 0.665). Exhaled ethylbenzene levels were too low to present
      a relationship between concentrations and personal exposure levels. The exhaled
      toluene, xylene and ethylbenzene concentrations ranged from 4.3 to 41.8, 0.9 to
      13.9, and 0.2 to 6.5 ppb, and the corresponding personal monitoring
      concentrations ranged from 60.3 to 572.3, 16.4 to 156.6, and 10.7 to 136.6,
      respectively. The average number of symptoms per person, according to neurotoxic
      questionnaire 16 (abbreviated as Q16) was 4.1 and six workers showed over six
      symptoms in Q16. This study suggests that exhaled toluene and xylene levels are
      suitable for use as biological exposure indices even at the ppb-level of
      exposure. Gasoline service workers are exposed to high levels of volatile organic
      compounds (VOCs) and the potential threats to their neurological systems deserve
      further investigation.

PMID- 12196002
TI  - Determination of Pb and Cd in road dusts over the period in which Pb was removed
      from petrol in the UK.
AB  - It is commonly agreed that automobile exhaust has been the most important source
      of Pb pollution in urban areas, and that Cd may come from wear and tear of tyres.
      This study evaluates the fall in Pb concentrations in road dusts in Manchester as
      a consequence of the removal of Pb from petrol in January 2000. In the work
      presented here a slurry graphite furnace atomic absorption methodology for the
      determination of Pb and Cd in road dusts has been developed and is compared with
      an acid digestion method in terms of efficiency. The reproducibility and accuracy
      of the results obtained by acid digestion and the slurry method have been studied
      and a certified reference material CRM 038 was analysed to confirm the
      reliability of the proposed methods. Different factors were evaluated throughout
      this work including: (i) the effect of traffic density on Pb and Cd levels in
      road dust samples collected weekly during the period of May 1999 until September
      2000; (ii) comparison between the Pb and Cd levels in a busy road and a
      residential street; (iii) the effect of distance from the source on Pb and Cd
      levels; The results of these experiments show a reduction in Pb levels over the
      sampling period. The relationship between road dust particle size and Pb and Cd
      concentration was also investigated in the 4-250 microns size range using the
      slurry method, showing that there is a relationship between metal concentration
      and particle size; the highest concentrations being for the smallest particle
      size.

PMID- 12196003
TI  - Nitrous acid concentrations in homes and offices in residential areas in Greater
      Cairo.
AB  - Indoor and outdoor measurements of nitrous acid and nitrogen dioxide were
      conducted at four homes and two offices in residential areas in Greater Cairo
      during winter (2000-2001) and summer (2001) seasons. Indoor nitrogen dioxide
      concentrations were higher than outdoor levels at the four homes, whereas indoor
      concentrations of nitrogen dioxide were lower than outdoor levels at the two
      offices, during both seasons. Indoor nitrous acid concentrations were higher than
      outdoor levels at all homes and offices during the period of study. The mean
      indoor nitrous acid concentrations were 6.8 ppb and 3.67 ppb in the four homes,
      whereas they were 1.42 ppb and 1.24 ppb in the two offices, during the winter and
      summer seasons, respectively. Indoor/outdoor ratios of nitrous acid concentration
      were 6.94 in the winter and 5.03 in the summer for all of the homes. However, the
      ratios were 1.31 and 1.61 during the winter and summer seasons, respectively, for
      the two offices. Insignificant positive correlation coefficients were found
      between indoor and outdoor concentrations of nitrous acid at homes and offices.
      The maximum outdoor nitrous acid concentrations were recorded during the winter
      season. Significant positive correlation coefficients were found between nitrous
      acid and nitrogen dioxide and relative humidity in homes and offices. The ratios
      of nitrous acid to nitrogen dioxide concentrations ranged from 0.045 to 0.16,
      with a mean of 0.1, in the four homes, whereas the ratios ranged from 0.026 to
      0.09, with a mean of 0.059, in the two offices.

PMID- 12196004
TI  - Effect of sample flow rate and sampling duration on the absorption of NO2 in the
      sodium arsenite monitoring method.
AB  - The effect of the two most critical parameters, the sample flow rate and sampling
      duration, on the absorption efficiency of NO2 in the sodium arsenite method of
      nitrogen dioxide determination in ambient air was studied. Laboratory experiments
      showed a high sensitivity to these parameters, which were subjected to variation
      during actual field monitoring. The reported NO2 absorption efficiency of the
      method of 82% at a flow rate of 0.2 l min-1 was found to be as low as 33% at a
      flow rate of 1.0 l min-1 for a sampling duration of 24 h. Similarly, a
      considerable decrease in absorption efficiency with increasing sampling duration
      from 2 to 24 h was observed at a particular flow rate. Correction factors for the
      absorption efficiency were evolved that can be used to update the existing
      database, as well as future NO2 data generated using this manual monitoring
      method.

PMID- 12196005
TI  - Radiological study of exposure levels in El Maghara underground coal mine.
AB  - Coal is largely composed of organic matter, but it is the inorganic matter in
      coal minerals and trace elements that have been cited as possible causes of
      health, environmental and technological problems associated with the use of coal.
      Some trace elements in coal are naturally radioactive. These radioactive elements
      include uranium (U), thorium (Th) and their numerous decay products, including
      radium (Ra) and radon (Rn). Although these elements are less chemically toxic
      than other coal constituents, such as arsenic, selenium or mercury, questions
      have been raised concerning the possible risk from radiation. In order to
      accurately address these questions and to predict the mobility of radioactive
      elements during the coal fuel cycle, it is important to determine the specific
      activity, distribution and form of radioactive elements in coal. The assessment
      of the radiation exposure from coal burning is critically dependent on the
      specific activity of radioactive elements in coal and in the fly ash that remains
      after combustion. The El-Maghara coal mine is the only producing coal mine in
      Egypt. It is located in the middle of the Sinai desert about 250 km north-east of
      Cairo, where a coal-fired power plant is intended to be built. In this study, a
      pre-operational radiological baseline of the site and the occupational radiation
      exposures due to radon progeny in the mine were determined. The specific
      activities of 226Ra, 232Th and 40K in soil and coal dust samples collected along
      the main gallery ranges were found to be 6-22.9, 9.6-47.3 and 77-489 Bq kg-1,
      respectively. Soil samples collected around the mine showed concentrations of
      226Ra, 232Th and 40K in the ranges 2.7-20.2, 3.2-12.6 and 14.6-201 Bq kg-1,
      respectively. All of the mean values of radon progeny were lower than the action
      levels for working places recommended in the International Commission on
      Radiological Protection (ICRP) 65.

PMID- 12196006
TI  - Uranium bioassay and radioactive dust measurements at some uranium processing
      sites in Egypt--health effects.
AB  - The safety of radiation workers in the uranium mining industry requires close and
      continuous monitoring of their working conditions. In this study, external
      radiation surveillance, radioactive dust monitoring and the bioassay of uranium
      were carried out in some processing sites. As dust represents one of the most
      important sources of radiation exposure in mills and mines, dust monitoring and
      bioassays were performed for a sample of workers on the production lines. The
      concentration of uranium in air ranged from 22.6 x 10(-7) to 11.1 x 10(-5) Bq cm
      3, and the exposure levels ranged from 1 to 80 microSv h-1. Laser fluorimetric
      determination of uranium in urine samples showed concentrations in the range 8.4
      29.2 micrograms L-1. Renal function parameters, such as serum creatinine and
      urea, and hematological parameters were determined in an attempt to correlate
      them with radiation exposure and the health status of the workers. Urine
      specimens collected from workers at the ore crushing and separation site showed
      elevated concentrations of uranium (up to 29.2 micrograms L-1) and a strong
      correlation between these concentrations and the registered serum creatinine. The
      mean uranium excretion in the investigated group was more than 20 times the
      occupational exposure decision level for urine uranium of 0.8 microgram L-1.

PMID- 12196007
TI  - Monitoring DNA damage in wood small-reed (Calamagrostis epigejos) plants growing
      in a sediment reservoir with substrates from uranium mining.
AB  - For most plant species growing in polluted areas genotoxicity assays are not
      available. We have studied the possibility of using the alkaline protocol of the
      Comet assay as a method for detecting induced DNA damage in a grass Calamagrostis
      epigejos, growing wild in highly polluted areas. To calibrate the Comet assay for
      C. epigejos, two model mutagens were applied: the monofunctional alkylating agent
      ethyl methanesulfonate (EMS) and gamma-rays. With increasing concentrations of
      EMS (0 to 10 mM, 18 h treatment at 26 degrees C) applied on excised leaves, the
      DNA damage, as expressed by the tail moment (TM) values, increased from 4.7 +/-
      0.9 to 60.8 +/- 2.7 microns. After gamma irradiation (0 to 30 Gy) the TM value
      increased from 4.2 +/- 0.2 to 48.1 +/- 1.7 microns. A 24 to 72 h recovery of
      leaves after EMS treatment in an EMS-free medium did not result in a significant
      change in the induced EMS damage. By contrast, a 24 h recovery after gamma
      irradiation led to a complete repair of DNA damage measurable by the Comet assay.
      We have measured the DNA damage in nuclei of leaves of C. epigejos plants growing
      in the area of a sediment reservoir with substrates from uranium mining, where
      the ore was exploited through leaching with sulfuric acid. The average specific
      activity of natural radionuclides measured in the substrate was for 226Ra =
      11,818 Bq kg-1, for 232Th = 66 Bq kg-1 and for 40K = 75 Bq kg-1. No significant
      increase in the DNA damage in plants growing on the sediment substrate above the
      DNA damage in control plants was detected by the Comet assay.

PMID- 12196008
TI  - Speciation of arsenic in plants by HPLC-HG-AFS: extraction optimisation on CRM
      materials and application to cultivated samples.
AB  - A recently developed method for the determination of arsenic species (arsenite,
      arsenate, monomethylarsonate, MMAA, and dimethylarsinate, DMAA) has been applied
      to the study of arsenic speciation in plants. This method uses ion-exchange
      liquid chromatography coupled on-line to atomic fluorescence spectrometry through
      continuous hydride generation. Various extraction procedures have been studied in
      detail using three plant certified reference materials. None of the procedures
      tested revealed fully satisfying results with all kinds of plant samples;
      microwave assisted extraction with 0.3 mol dm-3 orthophosphoric acid was found to
      be the most convenient for dealing with terrestrial plants. Species stability
      appears good. This method was applied to real world cultivated plant parts.
      Arsenate appears to predominate in soils, roots and leaves; unidentified species
      (probably arsenosugars) play an important role (60%) in rice fruits. Carrot was
      found to be the most contaminated edible plant part, containing 1 mg kg-1
      essentially as arsenate species. MMAA was detected in all soils and some plant
      parts especially shallots at low levels, whereas DMAA was found only in one soil
      sample and in hot pepper leaves. Arsenite is a minor component of all soils; it
      is also present in some plant parts at low levels. However, no evident
      relationships were found between As speciation in the various plant parts and
      much more detailed studies will be necessary to elucidate As behaviour in plants.

PMID- 12196009
TI  - Arsenic-speciation in arsenate-resistant and non-resistant populations of the
      earthworm, Lumbricus rubellus.
AB  - Arsenic speciation was determined in Lumbricus rubellus Hoffmeister from arsenic
      contaminated mine spoil sites and an uncontaminated site using HPLC-MS, HPLC-ICP
      MS and XAS. It was previously demonstrated that L. rubellus from mine soils were
      more arsenate resistant than from the uncontaminated site and we wished to
      investigate if arsenic speciation had a role in this resistance. Earthworms from
      contaminated sites had considerably higher arsenic body burdens (maximum 1,358 mg
      As kg-1) compared to the uncontaminated site (maximum 13 mg As kg-1). The only
      organo-arsenic species found in methanol/water extracts for all earthworm
      populations was arsenobetaine, quantified using both HPLC-MS and HPLC-ICP-MS.
      Arsenobetaine concentrations were high in L. rubellus from the uncontaminated
      site when concentrations were expressed as a percentage of the total arsenic
      burden (23% mean), but earthworms from the contaminated sites with relatively low
      arsenic burdens also had these high levels of arsenobetaine (17% mean). As
      arsenic body burden increased, the percentage of arsenobetaine present decreased
      in a dose dependent manner, although its absolute concentration rose with
      increasing arsenic burden. The origin of this arsenobetaine is discussed. XAS
      analysis of arsenic mine L. rubellus showed that arsenic was primarily present as
      As(III) co-ordinated with sulfur (30% approx.), with some As(v) with oxygen (5%).
      Spectra for As(III) complexed with glutathione gave a very good fit to the
      spectra obtained for the earthworms, suggesting a role for sulfur co-ordination
      in arsenic metabolism at higher earthworm arsenic burdens. It is also possible
      that the disintegration of As(III)-S complexes may have taken place due to (a)
      processing of the sample, (b) storage of the extract or (c) HPLC anion exchange.
      HPLC-ICP-MS analysis of methanol extracts showed the presence of arsenite and
      arsenate, suggesting that these sulfur complexes disintegrate on extraction. The
      role of arsenic speciation in the resistance of L. rubellus to arsenate is
      considered.

PMID- 12196010
TI  - Persistent chlorinated pesticides in fish and cattle fat and their implications
      for human serum concentrations from the Sene-Gambian region.
AB  - The concentrations of organochlorine pesticides (OCPs) in fish, shrimps, cattle
      fat and human serum samples from the Sene-Gambian region were measured using
      validated analytical methodologies. The results obtained were compared with those
      of other existing African studies and with data from other developing countries.
      In fish samples, p,p'-dichlorodiphenyldichloroethylene (p,p'-DDE) and HCB were
      detected with a frequency of 100%, whereas p,p'-dichlorodiphenyltrichloroethane
      (p,p'-DDT) was detected in eight, heptachlorepoxide in six and endosulfansulfate
      in five of the nine fish samples. Relatively low concentrations of OCPs were
      found in cattle and shrimp fat samples. p,p'-DDE and alpha-hexachlorocyclohexane
      (alpha-HCH) were the most frequently identified. The sum of HCHs ranged from
      undetected to 13.3 ng g-1 fat, the sum of DDTs from 11.1 to 199.2 ng g-1 fat and
      the sum of endosulfans from not detected to 49.7 ng g-1 fat in fish and shrimps.
      In serum samples, alpha-HCH, p,p'-DDE, o,p'-DDT and p,p'-DDT were detected in all
      16 pooled serum samples, whereas endosulfansulfate, methoxychlor, mirex,
      heptachlorepoxide and endrin were detected in 15 samples with most of the
      concentrations below 10 ng mL-1. The concentrations of OCPs in human serum were
      given on a serum lipid and whole serum volume basis. The implications for the
      human diet of these OCP concentrations in serum were investigated by means of
      biomagnification factors related to the log Kow values of the targeted compounds.
      The current use of HCH mixtures was suggested to explain the unusually high alpha
      HCH concentration. The distribution pattern of these OCPs in humans was also
      discussed and compared with that in other studies.

PMID- 12196011
TI  - Substrate binding induces a cooperative conformational change in the 12S subunit
      of transcarboxylase: Raman crystallographic evidence.
AB  - The 12S subunit of transcarboxylase is a 338 000 Da hexamer that transfers
      carboxlylate from methylmalonyl-CoA (MM-CoA) to biotin; in turn, the biotin
      transfers the carboxylate to pyruvate on another subunit, the 5S. Here, Raman
      difference microscopy is used to study the binding of substrate and product, and
      their analogues, to single crystals of 12S. A single crystal is the medium of
      choice because it provides Raman data of unprecedented quality. Crystalline
      ligand-protein complexes were formed by cocrystallization or by the soaking
      in/soaking out method. Raman difference spectra were obtained by subtracting the
      spectrum of the apo crystal from that of a crystal with the substrate or product
      bound. Raman difference spectra from crystals with the substrate bound are
      dominated by bands from the protein's amide bonds and aromatic side chain
      residues. In contrast, Raman difference spectra involving the product, propionyl
      CoA, are dominated by modes from the ligand. These results show that substrate
      binding triggers a conformational change in 12S, whereas product binding does
      not. The conformational change involves an increase in the amount of alpha-helix
      since markers for this secondary structure are prominent in the difference
      spectra of the substrate complex. The number of MM-CoA ligands bound per 12S
      hexamer can be gauged from the intensity of the MM-CoA Raman features and the
      fact that the protein concentration in the crystals is known from X-ray
      crystallographic data. Most crystal samples had six MM-CoAs per hexamer although
      a few, from different soaking experiments, contained only 1-2. However, both sets
      of crystals showed the same degree of protein conformational change, indicating
      that the change induced by the substrate is cooperative. This effect allowed us
      to record the Raman spectrum of bound MM-CoA without interference from protein
      modes; the Raman spectrum of a 12S crystal containing 2 MM-CoA ligands per
      hexamer was subtracted from the Raman spectrum of a 12S crystal containing six MM
      CoA ligands per hexamer. The conformational change is reversible and can be
      controlled by soaking out or soaking in the ligand, using either concentrated
      ammonium sulfate solutions or the solution used in the crystallization trials.
      Malonyl-CoA also binds to 12S crystals and brings about conformational changes
      identical to those seen for MM-CoA; in addition, butyryl-CoA binds and behaves in
      a manner similar to propionyl-CoA. These data implicate the -COO- group on MM-CoA
      (that is transferred to biotin in the reaction on the intact enzyme) as the agent
      bringing about the cooperative conformational change in 12S.

PMID- 12196012
TI  - Identification of neurite outgrowth promoting sites on the laminin alpha 3 chain
      G domain.
AB  - Laminins are expressed in specific tissues and are involved in various biological
      activities including promoting cell adhesion, growth, migration, neurite
      outgrowth, and differentiation. The laminin alpha3 chain is mainly located in the
      skin and is also expressed in the floor plate of the developing neural tube.
      Previously, we showed that the human laminin alpha3 chain LG4 module binds to
      syndecan-2/4, a membrane-associated proteoglycan, and promotes human fibroblast
      adhesion. Here, we have evaluated the neurite outgrowth activity of the laminin
      alpha3 chain LG4 and LG5 modules. Three overlapping recombinant proteins, which
      contained LG4 and/or LG5 modules of the human laminin alpha3 chain, were prepared
      using a mammalian cell expression system. Two proteins, rec-alpha3LG4-5 and rec
      alpha3LG4, promoted cell attachment and neurite outgrowth of rat pheochromocytoma
      PC12 cells, but rec-alpha3LG5 was inactive. Twenty-two peptides covering the
      entire LG4 module were synthesized and tested for cell attachment and neurite
      outgrowth activity to identify active sites of the LG4 module. A3G75
      (KNSFMALYLSKG, alpha3 chain 1411-1422) and A3G83 (GNSTISIRAPVY, alpha3 chain 1476
      1487) promoted PC12 cell attachment and neurite outgrowth. Additionally, A3G75
      and A3G83 inhibited PC12 cell attachment to rec-alpha3LG4. These results suggest
      that the A3G75 and A3G83 sites are important for PC12 cell attachment and neurite
      outgrowth in the laminin alpha3 chain LG4 module. We also conjugated the A3G75
      and A3G83 peptides on chitosan membranes to test their potential as bio
      materials. These peptide-conjugated chitosan membranes were more active for
      neurite outgrowth than the peptide-coated plates. These results suggest that the
      A3G75- and A3G83-conjugated chitosan membranes are applicable as bio-medical
      materials for neural tissue repair and engineering.

PMID- 12196013
TI  - Electrostatic contributions to site specific DNA cleavage by EcoRV endonuclease.
AB  - Mutational analysis of amino acids at the periphery of the EcoRV endonuclease
      active site suggests that moderate-range electrostatic effects play a significant
      role in modulating the efficiency of phosphoryl transfer. Asp36 and Lys38 located
      on minor-groove binding surface loops approach within 7-9 A of the scissile
      phosphates of the DNA. While the rates of single-site mutations removing the
      carboxylate or amine moieties at these positions are decreased 10(3)-10(5)-fold
      compared to that of wild-type EcoRV, we find that double mutants which rebalance
      the charge improve catalysis by up to 500-fold. Mutational analysis also suggests
      that catalytic efficiency is influenced by Lys173, which is buried at the base of
      a deep depression penetrating from a distal surface of the enzyme. The Lys173
      amine group lies just 6 A from the amine group of the conserved essential Lys92
      side chain in the active site. Kinetic and crystallographic analyses of the EcoRV
      E45A mutant enzyme further show that the Glu45 carboxylate group facilitates an
      extensive set of conformational transitions which occur upon DNA binding. The
      crystal structure of E45A bound to DNA and Mn2+ ions reveals significant
      conformational alterations in a small alpha-helical portion of the dimer
      interface located adjacent to the DNA minor groove. This leads to a tertiary
      reorientation of the two monomers as well as shifting of the key major-groove
      binding recognition loops. Because the Glu45 side chain does not appear to play a
      direct structural role in maintaining the active site, these rearrangements may
      instead originate in an altered electrostatic potential caused by removal of the
      negative charge. A Mn2+ binding site on the scissile phosphate is also disrupted
      in the E45A structure such that inner-sphere metal interactions made by the
      scissile DNA phosphate and conserved Asp90 carboxylate are each replaced with
      water molecules in the mutant. These findings argue against a proposed role for
      Asp36 as the general base in EcoRV catalysis, and reveal that the induced-fit
      conformational changes necessary for active site assembly and metal binding are
      significantly modulated by the electrostatic potential in this region.

PMID- 12196014
TI  - Cloning, overexpression, and purification of aminoglycoside antibiotic 3
      acetyltransferase-IIIb: conformational studies with bound substrates.
AB  - Aminoglycoside 3-acetyltransferase-IIIb (AAC3), which acetylates N3 amine of
      aminoglycoside antibiotics, was cloned from P. Aeruginosa and purified from
      overexpressing E. coli BL21 (DE3) cells. Bound conformations of kanamycin A and
      ribostamycin, in the active site of the enzyme that modifies the essential N3B of
      aminoglycoside antibiotics, were determined by NMR spectroscopy. Experimentally
      determined interproton distances were used in a simulated annealing protocol to
      determine enzyme-bound conformations of both antibiotics. Two conformations,
      consistent with the NOE restraints, were determined for ribostamycin. The only
      difference between the two conformers was the orientation of the A ring with
      respect to the rest of the molecule. The average glycosidic dihedral angles were
      Phi(1A) = -22 degrees +/- 3 and Psi(1A) = -42 degrees +/- 1 (conformer 1) and
      Phi(1A) = -67 degrees +/- 0.7 and Phi(1A) = -59 degrees +/- 0.8 (conformer 2).
      Three conformers were determined for the enzyme-bound kanamycin A. Two conformers
      of kanamycin A were matched well with the two conformers of ribostamycin when the
      A and the B rings of the antibiotics were superimposed. Conformations of
      kanamycin A and ribostamycin were compared to those of other aminoglycosides that
      are bound to different enzymes and RNA. The results lend further support to our
      earlier hypothesis that the A and B rings of aminoglycosides adopt a conformation
      that is recognized not only by the aminoglycoside-modifying enzymes but also by
      RNA (Serpersu, E. H., Cox, J. R., Digiammarino, E. L., Mohler, M. L., Akal, A.,
      Ekman, D. R., and Owston, M. (2000) Cell Biochem. Biophys. 33, 309-321). These
      results may be useful in designing new antibiotics to combat the antibiotic
      resistance against infectious diseases.

PMID- 12196015
TI  - Lipids in the structure, folding, and function of the KcsA K+ channel.
AB  - Lipid molecules surround an ion channel in its native environment of cellular
      membranes. The importance of the lipid bilayer and the role of lipid protein
      interactions in ion channel structure and function are not well understood. Here
      we demonstrate that the bacterial potassium channel KcsA binds a negatively
      charged lipid molecule. We have defined the potential binding site of the lipid
      molecule on KcsA by X-ray crystallographic analysis of a complex of KcsA with a
      monoclonal antibody Fab fragment. We also demonstrate that lipids are required
      for the in vitro refolding of the KcsA tetramer from the unfolded monomeric
      state. The correct refolding of the KcsA tetramer requires lipids, but it is not
      dependent on negatively charged lipids as refolding takes place in the absence of
      such lipids. We confirm that the presence of negatively charged lipids is
      required for ion conduction through the KcsA potassium channel, suggesting that
      the lipid bound to KcsA is important for ion channel function.

PMID- 12196016
TI  - Human glutathione-dependent formaldehyde dehydrogenase. Structures of apo,
      binary, and inhibitory ternary complexes.
AB  - The human glutathione-dependent formaldehyde dehydrogenase is unique among the
      structurally studied members of the alcohol dehydrogenase family in that it
      follows a random bi bi kinetic mechanism. The structures of an apo form of the
      enzyme, a binary complex with substrate 12-hydroxydodecanoic acid, and a ternary
      complex with NAD+ and the inhibitor dodecanoic acid were determined at 2.0, 2.3,
      and 2.3 A resolution by X-ray crystallography using the anomalous diffraction
      signal of zinc. The structures of the enzyme and its binary complex with the
      primary alcohol substrate, 12-hydroxydodecanoic acid, and the previously reported
      binary complex with the coenzyme show that the binding of the first substrate
      (alcohol or coenzyme) causes only minor changes to the overall structure of the
      enzyme. This is consistent with the random mechanism of the enzyme where either
      of the substrates binds to the free enzyme. The catalytic-domain position in
      these structures is intermediate to the "closed" and "open" conformations
      observed in class I alcohol dehydrogenases. More importantly, two different
      tetrahedral coordination environments of the active site zinc are observed in
      these structures. In the apoenzyme, the active site zinc is coordinated to Cys44,
      His66 and Cys173, and a water molecule. In the inhibitor complex, the
      coordination environment involves Glu67 instead of the solvent water molecule.
      The coordination environment involving Glu67 as the fourth ligand likely
      represents an intermediate step during ligand exchange at the active site zinc.
      These observations provide new insight into metal-assisted catalysis and
      substrate binding in glutathione-dependent formaldehyde dehydrogenase.

PMID- 12196017
TI  - Locking the hydrophobic loop 262-274 to G-actin surface by a disulfide bridge
      prevents filament formation.
AB  - Models of F-actin structure predict the importance of hydrophobic loop 262-274 at
      the interface of subdomains 3 and 4 to interstrand interactions in filaments. If
      this premise is correct, prevention of the loop conformational change--its
      swinging motion--should abort filament formation. To test this hypothesis, we
      used site-directed mutagenesis to create yeast actin triple mutant (LC)2CA
      (L180C/L269C/C374A). This mutation places two cysteine residues in positions
      potentially enabling the locking of loop 262-274 to the monomer surface via
      disulfide formation. Exposure of the purified mutant to oxidation catalysts
      resulted in an increased electrophoretic mobility of actin on SDS PAGE and a loss
      of two cysteines by DTNB titrations, consistent with disulfide formation. The
      polymerization of un-cross-linked mutant actin by MgCl2 was inhibited strongly
      but could be restored to wild type actin levels by phalloidin and improved
      greatly through copolymerization with the wild-type actin. Light scattering
      measurements revealed nonspecific aggregation of the cross-linked actin under the
      same conditions. Electron microscopy confirmed the absence of filaments and the
      presence of amorphous aggregates in the cross-linked actin samples. Reduction of
      the disulfide bond by DTT restored normal actin polymerization in the presence of
      MgCl2 and phalloidin. These observations provide strong experimental support for
      a critical role of the hydrophobic loop 262-274 in the polymerization of actin
      into filaments.

PMID- 12196018
TI  - The entry point of the K-proton-transfer pathway in cytochrome c oxidase.
AB  - Cytochrome c oxidase is a redox-driven proton pump. The enzyme has two proton
      input pathways, leading from the solution on the N-side to the binuclear center.
      One of these pathways, the K-pathway, is used for proton uptake upon reduction of
      the binuclear center. It is also important for local charge compensation during
      reaction of the fully reduced enzyme with O2. Two different locations have been
      proposed to constitute the entry point of the K-pathway: near S(I-299) or near
      E(II-101), respectively, in the Rhodobacter sphaeroides enzyme. The experiments
      discussed in this study are aimed at identifying the location of the entry point.
      The kinetics and extent of flash-induced proton release coupled to oxidation of
      heme a3 (tau congruent with 2 ms at pH 8.8 in the wild-type enzyme) in the
      absence of O2 were investigated in the ED(II-101), SD(I-299), and KM(I-362)
      mutant enzymes, i.e., at the two proposed entry points and in the middle of the
      pathway, respectively. This reaction was completely blocked in KM(I-362), while
      it was slowed by factors of 25 and 40 in the ED(II-101) and SD(I-299) mutant
      enzymes, respectively. During reaction of the fully reduced enzyme with O2,
      electron transfer from heme a to the catalytic site (during P(R)-formation) was
      blocked in the KM(I-362) and SD(I-299)/SG(I-299) but not in the ED(II-101)/ EA(II
      101) mutant enzymes. The results are interpreted as follows: Residue K(I-362) is
      involved in both proton transfer and charge compensation (in different reaction
      steps). The impaired proton release in the S(I-299) mutant enzymes is an indirect
      effect due to an altered environment of K(I-362). E(II-101), on the other hand,
      is likely to be part of the K-pathway since mutation of this residue results in
      impaired proton release but does not affect the P(R) formation kinetics; i.e.,
      the properties of K(I-362) are not altered. Consequently, we conclude that the
      entry point of the K-pathway is located near E(II-101).

PMID- 12196019
TI  - Early steps of the intramolecular signal transduction in rhodopsin explored by
      molecular dynamics simulations.
AB  - We present molecular dynamics simulations of bovine rhodopsin in a membrane
      mimetic environment based on the recently refined X-ray structure of the pigment.
      The interactions between the protonated Schiff base and the protein moiety are
      explored both with the chromophore in the dark-adapted 11-cis and in the
      photoisomerized all-trans form. Comparison of simulations with Glu181 in
      different protonation states strongly suggests that this loop residue located
      close to the 11-cis bond bears a negative charge. Restrained molecular dynamics
      simulations also provide evidence that the protein tightly confines the absolute
      conformation of the retinal around the C12-C13 bond to a positive helicity. 11
      cis to all-trans isomerization leads to an internally strained chromophore, which
      relaxes after a few nanoseconds by a switching of the ionone ring to an
      essentially planar all-trans conformation. This structural transition of the
      retinal induces in turn significant conformational changes of the protein
      backbone, especially in helix VI. Our results suggest a possible molecular
      mechanism for the early steps of intramolecular signal transduction in a
      prototypical G-protein-coupled receptor.

PMID- 12196020
TI  - X-ray structures of Torpedo californica acetylcholinesterase complexed with (+)
      huperzine A and (-)-huperzine B: structural evidence for an active site
      rearrangement.
AB  - Kinetic and structural data are presented on the interaction with Torpedo
      californica acetylcholinesterase (TcAChE) of (+)-huperzine A, a synthetic
      enantiomer of the anti-Alzheimer drug, (-)-huperzine A, and of its natural
      homologue (-)-huperzine B. (+)-Huperzine A and (-)-huperzine B bind to the enzyme
      with dissociation constants of 4.30 and 0.33 microM, respectively, compared to
      0.18 microM for (-)-huperzine A. The X-ray structures of the complexes of (+)
      huperzine A and (-)-huperzine B with TcAChE were determined to 2.1 and 2.35 A
      resolution, respectively, and compared to the previously determined structure of
      the (-)-huperzine A complex. All three interact with the "anionic" subsite of the
      active site, primarily through pi-pi stacking and through van der Waals or C-H.pi
      interactions with Trp84 and Phe330. Since their alpha-pyridone moieties are
      responsible for their key interactions with the active site via hydrogen bonding,
      and possibly via C-H.pi interactions, all three maintain similar positions and
      orientations with respect to it. The carbonyl oxygens of all three appear to
      repel the carbonyl oxygen of Gly117, thus causing the peptide bond between Gly117
      and Gly118 to undergo a peptide flip. As a consequence, the position of the main
      chain nitrogen of Gly118 in the "oxyanion" hole in the native enzyme becomes
      occupied by the carbonyl of Gly117. Furthermore, the flipped conformation is
      stabilized by hydrogen bonding of Gly117O to Gly119N and Ala201N, the other two
      functional elements of the three-pronged "oxyanion hole" characteristic of
      cholinesterases. All three inhibitors thus would be expected to abolish
      hydrolysis of all ester substrates, whether charged or neutral.

PMID- 12196021
TI  - Inhibitors of metalloendopeptidase EC 3.4.24.15 and EC 3.4.24.16 stabilized
      against proteolysis by the incorporation of beta-amino acids.
AB  - The enzyme EC 3.4.24.15 (EP 24.15) is a zinc metalloendopeptidase whose precise
      function in vivo remains unknown but is thought to participate in the regulated
      metabolism of a number of specific neuropeptides. The lack of stable and
      selective inhibitors has hindered the determination of the exact function of EP
      24.15. Of the limited number of EP 24.15 inhibitors that have been developed, N
      [1-(R,S)-carboxy-3-phenylpropyl]-Ala-Ala-Tyr-p-aminobenzoate (CFP) is the most
      widely studied. CFP is a potent and specific inhibitor, but it is unstable in
      vivo due to cleavage between the alanine and tyrosine residues by the enzyme
      neprilysin (EP 24.11). This cleavage by EP 24.11 generates a potent inhibitor of
      angiotensin converting enzyme, thereby limiting the use of CFP for in vivo
      studies. To develop specific inhibitors of EP 24.15 that are resistant to in
      vitro and potentially in vivo proteolysis by EP 24.11, this study incorporated
      beta-amino acids replacing the Ala-Tyr scissile alpha-amino acids of CFP. Both C2
      and C3 substituted beta-amino acids were synthesized and substituted at the EP
      24.11 scissile Ala-Tyr bond. Significant EP 24.15 inhibitory activity was
      observed with some of the beta-amino acid containing analogues. Moreover, binding
      to EP 24.11 was eliminated, thus rendering all analogues containing beta-amino
      acids resistant to degradation by EP 24.11. Selective inhibition of either EP
      24.15 or EP 24.16 was also observed with some analogues. The results demonstrated
      the use of beta-amino acids in the design of inhibitors of EP 24.15 and EP 24.16
      with K(i)'s in the low micromolar range. At the same time, these analogues were
      resistant to cleavage by the related metalloendopeptidase EP 24.11, in contrast
      to the alpha-amino acid based parent peptide. This study has therefore clearly
      shown the potential of beta-amino acids in the design of stable enzyme inhibitors
      and their use in generating molecules with selectivity between closely related
      enzymes.

PMID- 12196022
TI  - An unexpected interaction between the modular polyketide synthases, erythromycin
      DEBS1 and pikromycin PikAIV, leads to efficient triketide lactone synthesis.
AB  - An unusual feature of the 6-module pikromycin polyketide synthase (PikPKS, PikAI
      PikAIV) of S. venezuelae is the ability to generate both 12- and 14-membered ring
      macrolides. The PikAIV component containing the last extension module and a
      thioesterase domain is responsible for generating both of these products. In the
      case of the 12-membered ring macrolide, an acyl-enzyme intermediate on PikAIII is
      able to efficiently "skip" the last extension step and is cyclized by the TE
      domain of PikAIV, presumably as a result of a PikAIII-PikAIV interaction. Herein
      we report that plasmid-based expression (pBK3) of DEBS1, which comprises the
      loading domain and the first two modules of the Saccharopolyspora erythrea 6
      deoxyerythronolide B synthase, in S. venezuelae leads to efficient 15 +/- 3 mg/L
      production of triketide lactone products (TKLs). Comparable levels of TKLs were
      observed with a plasmid (pBK1) which expressed DEBS1 fused to a TE domain (DEBS1
      TE). These results are in stark contrast to previous in vivo and in vitro
      analyses, where only DEBS1-TE efficiently produces TKLs. Levels of TKLs decreased
      dramatically with expression of DEBS1 in both pikAIV and pikAIII-pikAIV deletion
      hosts (0.5 mg/L), but not DEBS1-TE, and could be partially restored by addition
      of a PikAIV complementation plasmid. These data suggest that PikAIV is able to
      efficiently catalyze formation of 6-membered lactone ring products from acyl
      bound intermediates on DEBS1 in a manner analogous to that observed for 12
      membered macrolide products from PikAIII. Significant sequence similarity and
      length of the C-terminal linker region of PikAIII and DEBS1 suggest that this
      region may be responsible for the interaction with PikAIV. A replacement of this
      linker region of DEBS1 with the corresponding region of PikAI led to a 95%
      decrease in TKL levels in S. venezuelae, consistent with this hypothesis.

PMID- 12196023
TI  - Mutational, kinetic, and NMR studies of the mechanism of E. coli GDP-mannose
      mannosyl hydrolase, an unusual Nudix enzyme.
AB  - GDP-mannose mannosyl hydrolase (GDPMH) is an unusual Nudix family member, which
      catalyzes the hydrolysis of GDP-alpha-D-mannose to GDP and the beta-sugar by
      nucleophilic substitution at carbon rather than at phosphorus (Legler, P. M.,
      Massiah, M. A., Bessman, M. J., and Mildvan, A. S. (2000) Biochemistry 39, 8603
      8608). Using the structure and mechanism of MutT, the prototypical Nudix enzyme
      as a guide, we detected six catalytic residues of GDPMH, three of which were
      unique to GDPMH, by the kinetic and structural effects of site-specific
      mutations. Glu-70 (corresponding to Glu-57 in MutT) provides a ligand to the
      essential divalent cation on the basis of the effects of the E70Q mutation which
      decreased kcat 10(2.2)-fold, increased the dissociation constant of Mn2+ from the
      ternary E-Mn2+-GDP complex 3-fold, increased the K(m)Mg2+ 20-fold, and decreased
      the paramagnetic effect of Mn2+ on 1/T1 of water protons, indicating a change in
      the coordination sphere of Mn2+. In the E70Q mutant, Gln-70 was shown to be very
      near the active site metal ion by large paramagnetic effects of Mn2+ on its side
      chain -NH2 group. With wild-type GDPMH, the effect of pH on log(kcat/K(m)GDPmann)
      at 37 degrees C showed an ascending limb of unit slope, followed by a plateau
      yielding a pK(a) of 6.4, which increased to 6.7 +/- 0.1 in the pH dependence of
      log(kcat). The general base catalyst was identified as a neutral His residue by
      the DeltaH(ionization) = 7.0 +/- 0.7 kcal/mol, by the increase in pK(a) with
      ionic strength, and by mutation of each of the four histidine residues of GDPMH
      to Gln. Only the H124Q mutant showed the loss of the ascending limb in the pH
      versus log(kcat) rate profile, which was replaced by a weak dependence of rate on
      hydroxide concentration, as well as an overall 10(3.4)-fold decrease in kcat,
      indicating His-124 to be the general base, unlike MutT, which uses Glu-53 in this
      role. The H88Q mutant showed a 10(2.3)-fold decrease in kcat, a 4.4-fold increase
      in K(m)GDPmann, and no change in the pH versus log(kcat) rate profile, indicating
      an important but unidentified role of His-88 in catalysis. One and two
      dimensional NMR studies permitted the sequence specific assignments of the
      imidazole HdeltaC, H(epsilon)C, N(delta), and N(epsilon) resonances of the four
      histidines and defined their protonation states. The pK(a) of His-124 (6.94 +/-
      0.04) in the presence of saturating Mg2+ was comparable to the kinetically
      determined pK(a) at the same temperature (6.40 +/- 0.20). The other three
      histidines were neutral N(epsilon)H tautomers with pK(a) values below 5.5. Arg-52
      and Arg-65 were identified as catalytic residues which interact electrostatically
      with the GDP leaving group by mutating these residues to Gln and Lys. The R52Q
      mutant decreased kcat 309-fold and increased K(m)GDPmann 40.6-fold, while the
      R52K mutant decreased kcat by only 12-fold and increased K(m)GDPmann 81-fold. The
      partial rescue of kcat, but not of K(m)GDPmann in the R52K mutant, suggests that
      Arg-52 is a bifunctional hydrogen bond donor to the GDP leaving group in the
      ground state and a monofunctional hydrogen bond donor in the transition state.
      Opposite behavior was found with the Arg-65 mutants, suggesting this residue to
      be a monofunctional hydrogen bond donor to the GDP leaving group in the ground
      state and a bifunctional hydrogen bond donor in the transition state. From these
      observations, a mechanism for GDPMH is proposed involving general base catalysis
      and electrostatic stabilization of the leaving group.

PMID- 12196024
TI  - Heterologous expression and characterization of human glutaminyl cyclase:
      evidence for a disulfide bond with importance for catalytic activity.
AB  - Glutaminyl cyclase (QC, EC 2.3.2.5) catalyzes the formation of pyroglutamate
      residues from glutamine at the N-terminus of peptides and proteins. In the
      current study, human QC was functionally expressed in the secretory pathway of
      Pichia pastoris, yielding milligram quantities after purification from the
      supernatant of a 5 L fermentation. Initial characterization studies of the
      recombinant QC using MALDI-TOF mass spectrometry revealed correct proteolytic
      processing and N-glycosylation at both potential sites with similar 2 kDa
      extensions. CD spectral analysis indicated a high alpha-helical content, which
      contrasts with plant QC from Carica papaya. The kinetic parameters for conversion
      of H-Gln-Tyr-Ala-OH by recombinant human QC were almost identical to those
      previously reported for purified bovine pituitary QC. However, the results
      obtained for conversion of H-Gln-Gln-OH, H-Gln-NH2, and H-Gln-AMC were found to
      be contradictory to previous studies on human QC expressed intracellularly in E.
      coli. Expression of QC in E. coli showed that approximately 50% of the protein
      did not contain a disulfide bond that is present in the entire QC expressed in P.
      pastoris. Further, the enzyme was consistently inactivated by treatment with 15
      mM DTT, whereas deglycosylation had no effect on enzymatic activity. Analysis of
      the fluorescence spectra of the native, reduced, and unfolded human QC point to a
      conformational change of the protein upon treatment with DTT. In terms of the
      different enzymatic properties, the consequences of QC expression in different
      environments are discussed.

PMID- 12196025
TI  - Properties of a soluble domain of subunit C of a bacterial nitric oxide
      reductase.
AB  - Bacterial nitric oxide reductases are integral membrane proteins that catalyze
      the reduction of two molecules of nitric oxide to nitrous oxide and water. They
      are diverged members of the superfamily of heme/copper oxidases. The enzyme from
      Paracoccus denitrificans (NorBC) contains two subunits; NorB comprises the
      membrane-integrated active site, which harbors a heme iron/non-heme iron
      dinuclear center. NorC is a membrane-anchored c-type cytochrome and presumably
      the site of electron uptake. A DNA construct encoding the water-soluble domain of
      NorC (NorC(sol)) was coexpressed with the cytochrome c maturation genes in
      Escherichia coli. Using redox potentiometry, electronic absorption, circular
      dichroism (CD), magnetic CD (MCD), nuclear magnetic resonance, and electron
      paramagnetic resonance (EPR) spectroscopy the following observations were made:
      (i) NorC(sol) was folded into a alpha-helical structure. (ii) The low-spin heme
      iron was coordinated by histidine and methionine in both redox states. (iii) The
      midpoint redox potential of the NorC(sol) heme was 183 mV, much lower than the
      corresponding value of 275 mV in the NorBC complex. This points to an increased
      solvent exposure of the NorC(sol) heme compared to in the native NorBC complex
      and shows that the electronic properties of NorC are modulated by NorB in the
      complex. (iv) The EPR and MCD spectra of NorC(sol) were considered alongside the
      spectra of NorBC, which has helped to resolve the contribution that different
      redox centers make in the holo-enzyme complex.

PMID- 12196026
TI  - Influence of gp41 fusion peptide on the kinetics of poly(ethylene glycol)
      mediated model membrane fusion.
AB  - The fusion peptide of the HIV fusion protein gp41 is required for viral fusion
      and entry into a host cell, but it is unclear whether this 23-residue peptide can
      fuse model membranes. We address this question for model membrane vesicles in the
      presence and absence of aggregating concentrations of poly(ethylene glycol)
      (PEG). PEG had no effect on the physical properties of peptide bound to membranes
      or free in solution. We tested for fusion of both highly curved and uncurved
      PC/PE/SM/CH (35:30:15:20 mol %) vesicles and highly curved PC/PE/CH (1:1:1)
      vesicles treated with peptide in the presence and absence of PEG. Fusion was
      never observed in the absence of PEG, although high peptide concentrations led to
      aggregation and rupture, especially in unstable PC/PE/CH (1:1:1) vesicles. When 5
      wt % PEG was present to aggregate vesicles, peptide enhanced the rate of lipid
      mixing between curved PC/PE/SM/CH vesicles in proportion to the peptide
      concentration, with this effect leveling off at peptide/lipid (P/L) ratios
      approximately 1:200. Peptide produced an even larger effect on the rate of
      contents mixing but inhibited contents mixing at P/L ratios >1:200. No fusion
      enhancement was seen with uncurved vesicles. The rate of fusion was also enhanced
      by the presence of hexadecane, and peptide-induced rate enhancement was not
      observed in the presence of hexadecane. We conclude that gp41 fusion peptide does
      not induce vesicle fusion at subrupturing concentrations but can enhance fusion
      between highly curved vesicles induced to fuse by PEG. The different effects of
      peptide on the rates of lipid mixing and fusion pore formation suggest that,
      while gp41 fusion peptide does affect hemifusion, it mainly affects pore
      formation.

PMID- 12196027
TI  - Mechanism of the beta-ketoacyl synthase reaction catalyzed by the animal fatty
      acid synthase.
AB  - The catalytic mechanism of the beta-ketoacyl synthase domain of the
      multifunctional fatty acid synthase has been investigated by a combination of
      mutagenesis, active-site titration, product analysis, and product inhibition.
      Neither the reactivity of the active-site Cys161 residue toward iodoacetamide nor
      the rate of unidirectional transfer of acyl moieties to Cys161 was significantly
      decreased by replacement of any of the conserved residues, His293, His331, or
      Lys326, with Ala. Decarboxylation of malonyl moieties in the fully-active
      Cys161Gln background generated equimolar amounts of acetyl-CoA and bicarbonate,
      rather than carbon dioxide, and was seriously compromised by replacement of any
      of the conserved basic residues. The ability of bicarbonate to inhibit
      decarboxylation of malonyl moieties in the Cys161Gln background was significantly
      reduced by replacement of His293 but less so by replacement of His331. The data
      are consistent with a reaction mechanism, in which the initial primer transfer
      reaction is promoted largely through a lowering of the pKa of the Cys161 thiol by
      a helix dipole effect and activation of the substrate thioester carbon atom by
      binding of the keto group in an oxyanion hole. The data also indicate that an
      activated water molecule is present at the active site that is required either
      for the rapid hydration of carbon dioxide, prior its release as bicarbonate or,
      alternatively, for an initial attack on the malonyl C3. In the alternative
      mechanism, a negatively-charged tetrahedral transition state could be generated,
      stabilized in part by interaction of His293 with the negatively charged oxygen at
      C3 and interaction of His331 with the negatively charged thioester carbonyl
      oxygen, that breaks down to generate bicarbonate directly. Finally, the carbanion
      at C2, attacks the electrophilic C1 of the primer, generating a second
      tetrahedral transition state, also stabilized through contacts with the oxyanion
      hole and His331, that breaks down to form the beta-ketoacyl-S-acyl carrier
      protein product.

PMID- 12196028
TI  - Analysis of the DNA-binding properties of MyoD, myogenin, and E12 by fluorescence
      anisotropy.
AB  - MyoD and Myogenin are dominant myogenic regulatory factors (MRFs), which are
      involved in control of muscle-specific gene expression. The ubiquitously
      expressed E12 dimerizes with MyoD and Myogenin and has been shown to enhance
      their DNA-binding and transcriptional activities. In this study, fluorescence
      anisotropy assays have been used to determine the Gibb's free energy of
      dissociation (DeltaG) for MyoD, Myogenin, and E12 as homo- and heterodimers to
      the well-characterized myosin light chain enhancer (MLC), muscle creatine kinase
      (MCK) enhancer, and mutant thereof. The heterodimers of MyoD or Myogenin with E12
      bound the MCK enhancer equally well (DeltaG = 21 kcal/mol). The homodimers varied
      dramatically in both MLC and MCK enhancer binding affinity. MyoD homodimer bound
      the MCK enhancer with the highest affinity (DeltaG = 19.6 kcal/mol) in comparison
      with the Myogenin homodimer-MCK interaction (DeltaG = 16.6 kcal/mol) and E12
      homodimer-MCK interaction (DeltaG = 18.0 kcal/mol). The slope and shape of the
      binding isotherms revealed that with the exception of the E12 homodimer-MCK
      enhancer interaction, the other proteins bound with high levels of positive
      cooperativity. In contrast, the E12 homodimer-MCK enhancer interaction actually
      occurs with significant negative cooperativity. The binding of these proteins to
      MLC enhancer mimicked binding to the MCK enhancer, but with much lower
      affinities. These data support the hypothesis that DNA acts as an allosteric
      ligand facilitating the dimerization of these proteins. The combination of
      differential affinity and cooperativity explains why the heterodimers are the
      active species in transcriptional regulation.

PMID- 12196029
TI  - Influence of racial origin and skeletal muscle properties on disease prevalence
      and physical performance.
AB  - Skeletal muscle properties are related to disease (e.g. obesity) and physical
      performance. For example, a predominance of type I muscle fibres is associated
      with better performance in endurance sports and a lower risk of obesity. Disease
      and physical performance also differ among certain racial groups. African
      Americans are more likely than Caucasians to develop obesity, diabetes mellitus
      and hypertension. Empirical studies indicate that aerobic capacity is lower in
      African Americans than Caucasians. Because genetics is a partial determinant of
      skeletal muscle properties, it is reasonable to assume that skeletal muscle
      properties vary as a function of race. As such, genetically determined and race
      specific skeletal muscle properties may partially explain racial disparities in
      disease and physical performance. However, additional research is needed in this
      area to enable the development of more definitive conclusions.

PMID- 12196031
TI  - Short-term muscle power during growth and maturation.
AB  - During growth and maturation, the study of very brief high-intensity exercise has
      not received the same attention from researchers as, for instance, aerobic
      function. In anaerobic tasks or sports events such as sprint cycling, jumping or
      running, the children's performance is distinctly lower than that of adults. This
      partly reflects children's lesser ability to generate mechanical energy from
      chemical energy sources during short-term intensive activity. For many years,
      various attempts have been made to quantify the anaerobic energy yield in maximal
      intensity exercise, but many assumptions have had to be made with respect to
      mechanical efficiency, lactate turnover, dilution space for lactate, and so on.
      During childhood and adolescence, direct measurements of the rate or capacity of
      anaerobic pathways for energy turnover presents several ethical and
      methodological difficulties. Thus, rather than measure energy supply, paediatric
      exercise scientists have concentrated on measuring short-term muscle power (STMP)
      by means of standardised tests. Previously, investigators have used various
      protocols such as short-term cycling power tests, vertical jump tests or running
      tests. Cycling ergometer tests are the most common. There is, however, no ideal
      test, and so it is important to acknowledge the limitations of each test.
      Progress has been made in assessing instantaneous cycling STMP from a single
      exercise bout. Several investigators have reported STMP increases with age and
      have suggested that late pubertal period may accentuate anaerobic glycolysis.
      Mass-related STMP was shown to increase dramatically during childhood and
      adolescence, whereas the corresponding increase in peak blood lactate was
      considerably lower. The latter results support the hypothesis that the difference
      observed between children and adolescents during STMP testing is more related to
      neuromuscular factors, hormonal factors and improved motor coordination, rather
      than being an indicator of reduced lactate-producing glycolysis mechanism.
      Evidence suggesting a causal link between the ability to generate lactate during
      exercise and sexual maturation is weak. Despite the majority of research being
      focused on short-term power output, the study of anaerobic function warrants more
      investigation. Spectacular progress is being made at the moment in the
      development of molecular biology tools that can be used in, for example, the
      genetic dissection of human performance phenotypes. Noninvasive power tools like
      magnetic resonance imaging and magnetic resonance spectroscopy are presently used
      to determine possible differences in phosphorus compounds between fast and slow
      fibre types. Undoubtedly these tools will lead to more information in the near
      future regarding STMP capabilities of the growing child.

PMID- 12196032
TI  - Exercise recommendations in athletes with early osteoarthritis of the knee.
AB  - Osteoarthritis of the knee is a common condition that afflicts millions of
      individuals annually. The benefits of exercise are self evident as athletes and
      middle-aged individuals grow older, and the focus has centered on pain-free
      participation in their sports and activities. In the past, medical treatment has
      primarily relied on oral medications to manage symptoms, without the
      incorporation of therapeutic exercise. Consequently, as the osteoarthritis
      progresses, patients are offered surgical management and eventual joint
      replacement. A goal-oriented progressive rehabilitation programme that
      incorporates medical management in the initial stages would allow patients a
      greater ability to participate in sports, thereby obtaining the numerous benefits
      of exercise and perhaps delaying surgery. A progressive rehabilitation programme
      consists of five stages (I to V). Medical management is primarily reserved for
      stage I: protected mobilisation and pain control. It entails the use of pain
      medications, nonsteroidal anti-inflammatory drugs, with or without the use of
      chondroprotective agents such as glucosamine. Injection therapy is usually
      incorporated at this stage with intra-articular injections of corticosteroids or
      viscosupplementation, either of which may be combined with minimally invasive
      single-needle closed joint lavage procedure. Stages II and III introduce open
      kinetic-chain nonweightbearing exercises to the affected joint, with progression
      to closed kinetic-chain exercises. Stage IV focuses on return to sporting
      activities, with continued closed kinetic-chain exercises. There is also the
      incorporation of sport-specific exercises to improve neuromuscular coordination,
      timing and protect against future injury. Finally, stage V, or the maintenance
      phase, is primarily aimed at educating the patient on how to reduce the risk of
      re-injury and optimise their current exercise programme. Medical management of
      knee osteoarthritis within the framework of a progressive rehabilitation
      programme that includes active therapeutic exercise may delay the progression of
      this disease and allow patients years of greater pain-free activity and improved
      quality of life.

PMID- 12196034
TI  - Need for care and perceptions of MIDAS among headache sufferers study.
AB  - INTRODUCTION: Patients with migraine have varying medical care needs. To
      effectively stratify patients to appropriate care, physicians should consider the
      frequency and intensity of attacks, and their overall impact on ability to
      function. The Migraine Disability Assessment Scale (MIDAS) measures headache
      related disability. The MIDAS Perceptions Study investigated whether MIDAS scores
      reflect headache severity and the need for medical care, and assessed whether the
      MIDAS questionnaire is meaningful and relevant to patients, and easy to use.
      DESIGN: The Perceptions Study was conducted as a follow-up to a baseline
      telephone interview. Upon completion of the baseline survey, 471 individuals were
      invited to participate in the Perceptions Study and 420 participated: 168
      patients with migraine headaches and 253 with non-migraine headaches. Patients
      with migraine or non-migraine headaches completed the MIDAS questionnaire and the
      Center of Epidemiologic Studies of Depression (CES-D) questionnaire, and were
      then interviewed by telephone within 48 hours of receiving the questionnaires.
      RESULTS: Headache frequency and pain intensity increased significantly with
      increasing MIDAS grade (p < 0.0001). A pattern of decreasing quality-of-life
      scores on the physical and mental subscales of the Short Form-12 was also seen
      with increasing MIDAS grade. Scores on the CES-D scale increased significantly
      with increasing MIDAS grade (p < 0.0001), indicating a greater likelihood of
      depression and more severe depression with higher grades. There were significant
      associations between increasing MIDAS grade and an increasing proportion of
      individuals who had consulted a doctor within the past year, lower use of over
      the-counter medication, and greater use of prescription medications (p < 0.0001
      for all three variables). Satisfaction with current therapy decreased
      significantly with increasing MIDAS grade, mirroring the frequency with which
      individuals achieved complete relief from headache. The MIDAS questionnaire was
      rated as easy to use by the vast majority of respondents, and ratings of its
      perceived value increased significantly as MIDAS grade increased. CONCLUSIONS: A
      low MIDAS score generally seems to indicate a low need for care, while
      individuals in MIDAS grades III and IV appear to have significant unmet medical
      care needs. The MIDAS questionnaire had increasingly perceived relevance as MIDAS
      grade increased, helped the majority of those in MIDAS grades III and IV to
      understand the impact of their headaches, and encouraged those with the greatest
      disability to seek medical care. The MIDAS questionnaire may facilitate
      communication between doctors and patients, and help physicians to identify those
      receiving inadequate medical care.

PMID- 12196036
TI  - Patient perceptions and treatment preferences in migraine management.
AB  - As the characteristics of migraine vary among patients and between attacks,
      multiple factors must be considered clinically to ensure that patients receive
      the most effective treatment strategy. Critical information required from the
      patient is general medical history, migraine-specific history, and the impact of
      migraine. Once the strategy of care and the optimal therapeutic plan are decided,
      the choice of therapeutic delivery must take into account patient preferences,
      compliance and clinical need. During the symposium, a case review and interview
      with a patient were conducted to illustrate the complex nature of integrating the
      assessment of signs, symptoms, disability, comorbidities and patient preferences.
      At the woman's first clinic visit, her Migraine Disability Assessment Scale
      (MIDAS) score was 70. Previous acute therapies had been only marginally
      effective, while previous prophylactic therapies had been discontinued because of
      adverse events or had also proved to be ineffective. The patient's current acute
      therapy was zolmitriptan 5mg, which she responds to well. Seven months after her
      first clinic visit, the patient's MIDAS score had decreased to 25. When asked
      about the relevance and utility of the MIDAS questionnaire, the patient felt that
      it asked about things that are important, helped her to understand the impact of
      migraine on her life, and accurately reflected her improvement. The patient also
      expressed an interest in trying more rapidly acting formulations of migraine
      specific therapies in the future, such as a nasal spray formulation of
      zolmitriptan. The MIDAS questionnaire facilitates communication between
      physicians and patients to enable greater understanding of the impact of
      migraine. MIDAS grades can also be used in the stratification of treatment and
      for monitoring the course of illness and treatment outcomes. By increasing
      available treatment options, patient needs and preferences can be matched with
      specific features of migraine therapies. Taking patient preferences into account
      is likely to increase patient satisfaction and compliance, hopefully decreasing
      the degree of undertreatment of migraine that has been reported globally.

PMID- 12196035
TI  - Global trends in migraine care: results from the MAZE survey.
AB  - INTRODUCTION: Many patients with migraine do not consult a physician, or do not
      achieve adequate relief after consulting a physician because of undertreatment.
      The objective of the Migraine and Zomig Evaluation study was to provide insights
      into the management of migraine in the general population. METHODS: In phase I,
      5553 members of the general public in the UK, France, Germany, Italy, and the US
      were interviewed by telephone and classified according to International Headache
      Society criteria. The Migraine Disability Assessment Scale (MIDAS) questionnaire
      was used to assess the impact of migraine on work, home and social lives. In
      phase II, 516 patients with clinically diagnosed migraine were interviewed to
      assess the impact of migraine on daily life, attitudes towards migraine,
      perceptions of current treatments and aspirations for future treatments. RESULTS:
      In phase I, the average prevalence of migraine over the five countries was 9%.
      Migraine posed a significant burden in terms of the impact on patients' daily
      lives, and attack severity and frequency. However, medical consultation rates
      were low; reasons for this included patients not recognising that they had
      migraine or having low expectations about treatment benefits. On average, only
      10% of patients who had consulted a physician had been prescribed a triptan. Only
      22% of participants in phase II thought that migraine did not markedly affect
      their lives. In each of the five countries, > or = 50% of patients required bed
      rest to manage migraine attacks, demonstrating the impact of migraine-related
      disability on patients' lives. Assessment of MIDAS scores confirmed the
      debilitating effect of migraine; > 50% of respondents had a MIDAS grade of III or
      IV, indicating moderate or severe disability. Less than one-third of patients
      reported that their current medication was consistently effective and only 36%
      were 'very satisfied' with their current therapy. High efficacy and rapid pain
      relief were rated as the most important attributes of migraine medications. When
      asked which formulation they would like to see more of, most patients chose a
      tablet that dissolves in the mouth without the need to take liquids. CONCLUSIONS:
      These results show that migraine patients worldwide are still not receiving
      adequate treatment and there remains a significant unmet need in migraine care.
      The challenge for the future is to diagnose migraine early and offer patients
      effective migraine-specific therapies. Physicians particularly need to reach
      patients who do not realise they have migraine and those who have lapsed from
      care.

PMID- 12196037
TI  - Gene therapy in infants with severe combined immunodeficiency.
AB  - Severe combined immunodeficiencies (SCID) are rare disorders that represent
      paediatric medical emergencies, as the outcome for affected patients can easily
      be fatal unless proper treatment is performed. The only curative treatment for
      SCID is reconstitution of the patient's immunity. For more than 30 years,
      allogeneic bone marrow transplantation (BMT) has been extremely successful for
      SCID. However, BMT often results in only incomplete restoration of B cell
      function in treated patients, especially when haploidentical donors are used. In
      addition, BMT can be associated with severe complications such as graft-versus
      host disease (GVHD). Alternative forms of therapy for SCID are therefore
      desirable. Genetic correction of peripheral T lymphocytes and/or haematopoietic
      stem cells (HSCs) by retrovirally mediated gene transfer has been attempted for
      patients with SCID due to adenosine deaminase deficiency, the first genetic
      disease targeted in clinical gene therapy trials with very limited success,
      overall. After these pioneer trials, recent progress has led to significant
      improvement of gene transfer techniques and better understanding of HSC biology
      which has culminated in the recent success of a gene therapy trial for patients
      affected with X-linked SCID (X-SCID). In this trial, patients with X-SCID
      received autologous bone marrow stem/progenitor cells which had been retrovirally
      transduced with a therapeutic gene. Based on the current follow-up, the overall
      efficacy of this gene therapy procedure is to be considered similar to or even
      better than that achievable by allogeneic BMT, because patients were not exposed
      to the risks of GVHD. Although these exciting results have clearly demonstrated
      that gene therapy is a feasible therapeutic option for X-SCID, they have also
      raised important questions regarding the long-term outcome of this experimental
      procedure and the possibility of translating this success into applications for
      other forms of SCID.

PMID- 12196030
TI  - Methods to determine aerobic endurance.
AB  - Physiological testing of elite athletes requires the correct identification and
      assessment of sports-specific underlying factors. It is now recognised that
      performance in long-distance events is determined by maximal oxygen uptake (V(2
      max)), energy cost of exercise and the maximal fractional utilisation of V(2 max)
      in any realised performance or as a corollary a set percentage of V(2 max) that
      could be endured as long as possible. This later ability is defined as endurance,
      and more precisely aerobic endurance, since V(2 max) sets the upper limit of
      aerobic pathway. It should be distinguished from endurance ability or endurance
      performance, which are synonymous with performance in long-distance events. The
      present review examines methods available in the literature to assess aerobic
      endurance. They are numerous and can be classified into two categories, namely
      direct and indirect methods. Direct methods bring together all indices that allow
      either a complete or a partial representation of the power-duration relationship,
      while indirect methods revolve around the determination of the so-called
      anaerobic threshold (AT). With regard to direct methods, performance in a series
      of tests provides a more complete and presumably more valid description of the
      power-duration relationship than performance in a single test, even if both
      approaches are well correlated with each other. However, the question remains
      open to determine which systems model should be employed among the several
      available in the literature, and how to use them in the prescription of training
      intensities. As for indirect methods, there is quantitative accumulation of data
      supporting the utilisation of the AT to assess aerobic endurance and to prescribe
      training intensities. However, it appears that: there is no unique intensity
      corresponding to the AT, since criteria available in the literature provide
      inconsistent results; and the non-invasive determination of the AT using
      ventilatory and heart rate data instead of blood lactate concentration ([La(
      )](b)) is not valid. Added to the fact that the AT may not represent the optimal
      training intensity for elite athletes, it raises doubt on the usefulness of this
      theory without questioning, however, the usefulness of the whole [La(-)](b)-power
      curve to assess aerobic endurance and predict performance in long-distance
      events.

PMID- 12196038
TI  - Biological imaging for the diagnosis of inflammatory conditions.
AB  - Radiopharmaceuticals used for in vivo imaging of inflammatory conditions can be
      conveniently classified into six categories according to the different phases in
      which the inflammatory process develops. The trigger of an inflammatory process
      is a pathogenic insult (phase I) that causes activation of endothelial cells
      (phase II); there is then an increase of vascular permeability followed by tissue
      oedema (phase III). Phase IV is characterised by infiltration of
      polymorphonuclear cells, and a self-limiting regulatory process called apoptosis
      is observed (phase V). If the inflammatory process persists, late chronic
      inflammation takes place (phase VI). In some pathological conditions, such as
      organ-specific autoimmune diseases, chronic inflammation is present early in the
      disease. The aim of nuclear medicine in the field of inflammation/infection is to
      develop noninvasive tools for the in vivo detection of specific cells and
      tissues. This would allow early diagnosis of initial pathophysiological changes
      that are undetectable by clinical examination or by other diagnostic tools, and
      could also be used to evaluate the state of activity of the disease during
      therapy. These potential applications are of great interest in clinical practice.
      In this review, we describe the various approaches that have been developed in
      the last 25 years of experience. Recent advances in the diagnosis of inflammatory
      processes have led to the development of specific radiopharmaceuticals that are
      intended to allow specific stage-related diagnosis.

PMID- 12196039
TI  - Potential of interferon-alpha in solid tumours: part 1.
AB  - Interferon-alpha (IFNalpha) is a pleiotropic cytokine with direct and indirect
      antitumour effects. These include prolongation of the cell cycle time of
      malignant cells, inhibition of biosynthetic enzymes and apoptosis, interaction
      with other cytokines, and immunomodulatory and antiangiogenic effects. The first
      clinical trials in solid tumours used crude preparations of natural IFNalpha and
      demonstrated that tumour regressions in solid tumours and haematological
      malignancies were possible. Since the advent of genetic engineering technology,
      recombinant (r) IFNalpha has been widely evaluated in solid tumours. This review
      discusses the use and potential of rIFNalpha in solid tumours; the first part
      focuses on malignant melanoma and metastatic renal cell carcinoma (RCC). In the
      adjuvant treatment of malignant melanoma, rIFNalpha has been tested in randomised
      trials in more than 6000 patients. High-dosage IFNalpha (> or =10MU) prolongs
      disease-free survival (DFS) but not overall survival (OS). Low-dosage IFNalpha (<
      or =3MU) has not been shown to prolong DFS or OS, and current data do not support
      its use outside clinical trials. The latest United Kingdom Co-ordinating
      Committee on Cancer Research meta-analysis of ten randomised trials that used
      adjuvant rIFNalpha has shown that there is a benefit in DFS but not OS. No
      conclusions can be reached for intermediate-dosage IFNalpha (5 to 10MU) until the
      mature results of the European Organization for Research and Treatment of Cancer
      (EORTC) study 18952 are available. In RCC, current evidence does not support the
      use of adjuvant IFNalpha. In metastatic malignant melanoma and RCC, reported
      response rates to rIFNalpha are approximately 15%. In a minority of responding
      patients, however, these responses can be long-standing. In metastatic malignant
      melanoma, IFNalpha combined with other cytotoxic agents with or without
      interleukin-2 has achieved high response rates but has not improved survival. In
      metastatic RCC, intermediate dosages of rIFNalpha should be used and therapy
      should probably be prolonged (>12 months); response depends on prognostic factors
      such as good performance status, whereas survival is affected by factors such as
      low tumour burden. Nephrectomy should therefore be considered in patients with
      good performance status prior to IFNalpha immunotherapy in advanced RCC, even in
      patients with metastatic disease. The toxicity of high-dosage IFNalpha and the
      lack of definite benefit on OS with high- or low-dosage IFNalpha do not support
      its use outside clinical trials. Data from the ongoing US Intergroup studies, the
      ongoing EORTC 18991 study (long-term therapy with pegylated IFNalpha) and mature
      data from EORTC 18952 (intermediate-dosage IFNalpha) will help establish the role
      of IFNalpha as adjuvant therapy in malignant melanoma.

PMID- 12196040
TI  - Monoclonal antibody therapy of haematological malignancies.
AB  - Over the past decade the potential for delivering targeted therapy against
      malignant disease by the use of monoclonal antibodies (MAbs) has begun to be
      realised. Haematological malignancies, because of the relative accessibility of
      the malignant cell in blood and bone marrow and the understanding of haemopoietic
      lineage-specific antigens, have provided a successful testing ground for this
      therapy. There have been many technical developments which have allowed the safe
      delivery of more potent antibody constructs. The development of human or chimeric
      antibodies has largely overcome the problems associated with host immune
      responses to rodent-derived MAbs. Protein engineering to combine MAbs with other
      biologically active molecules such as radioisotopes, toxins, chemotherapy and
      cytokines, has made available a new range of agents with clinical activity. The
      purpose of this review is not to give a catalogue of all therapeutic antibodies
      but rather to outline the principles of this approach, the current state of
      knowledge, and possible directions for future development. First, the general
      requirements and strategies for use of both unmodified and conjugated MAbs are
      discussed, followed by a summary of the trial data in specific lymphoid and
      myeloid haemopoietic malignancies. The focus is on MAbs that now have an accepted
      use in clinical practice, with some discussion of newer MAbs under development.
      Vaccination strategies and the role of MAbs in bone marrow transplantation are
      not discussed in detail. The trials of the next decade will address issues such
      as: whether clinical activity translates into improved survival; the optimal
      strategies and timing for clinical use; whether increasing potency of MAbs (as in
      radio- and immunoconjugates) will increase toxicity and, finally, what other
      potential molecules, such as those influencing cell growth and death, may be
      targeted.

PMID- 12196041
TI  - Anakinra.
AB  - Anakinra, a recombinant human interleukin-1 (IL-1) receptor antagonist, is the
      first biological agent approved to block the pro-inflammatory effects of IL-1 in
      patients with rheumatoid arthritis. In a double-blind, randomised trial in 472
      patients with active, severe or very severe rheumatoid arthritis, recipients of
      subcutaneous anakinra 150 mg/day achieved higher response rates [assessed using
      the American College of Rheumatology (ACR) composite score] and accumulated more
      mean productivity days after 6 months than placebo recipients. However, the
      response rates and accumulated productivity days of patients receiving
      subcutaneous anakinra 30 or 75 mg/day for 6 months were similar to those of
      placebo. With respect to the total Genant radiographic scores, the same study
      showed that all anakinra treatment regimens slowed disease progression after 6
      months to a greater extent than placebo. In double-blind, randomised trials in
      patients with rheumatoid arthritis, combined treatment with anakinra and
      methotrexate was associated with higher ACR 20, 50 and 70 response rates than
      with methotrexate alone. Anakinra, used alone or in combination with
      methotrexate, was generally well tolerated, with the most frequent adverse event
      being a mild injection-site reaction of transient duration. Infections requiring
      antibacterial therapy or hospitalisation occurred more commonly in anakinra
      recipients than in placebo recipients, but were a rare cause for discontinuation
      of anakinra therapy (approximately 1%) in clinical trials.

PMID- 12196045
TI  - Laronidase.
AB  - BioMarin Pharmaceutical is developing laronidase, recombinant alpha-L-iduronidase
      enzyme replacement therapy for the treatment of mucopolysaccharidosis I (MPS-I)
      [the most severe form of this is called Hurler syndrome]. The company has
      received US and European orphan drug designation for the enzyme and has fast
      track review status with the FDA. In 1998, BioMarin Pharmaceutical and Genzyme
      General formed a joint venture for development and marketing of laronidase. A
      Phase I trial in 10 patients with a range of disease severity of MPS-I required
      for US and European filing was completed at the Harbor-UCLA Medical Center in
      California. This open label trial involved weekly infusions with laronidase. The
      two-year follow-up data revealed sustained and, in certain parameters, improved
      clinical results recorded at the end of 1 year of therapy. BioMarin and Genzyme
      General have completed a pivotal, Phase III trial in the centres in the USA,
      Canada and Europe, including patients with Hurler-Scheie and Scheie syndromes. In
      a multicentre, double-blind, placebo-controlled study, all 45 patients with MPS-I
      have received at least their initial weekly infusion of laronidase. Patients are
      being evaluated over a 6-month period. BioMarin Pharmaceutical and Genzyme
      General have filed on 15 April 2002 the first portion of a 'rolling' BLA with the
      US FDA for use of laronidase in the treatment of MPS-I. The companies are
      planning to complete the BLA filing in Q3 2002. The application will include 6
      month data from the ongoing open-label Phase III extension study and also the 6
      month data from the placebo-controlled part of the Phase III study. In the open
      label extension study, patients from both the treatment and placebo arms of the
      Phase III trial received weekly infusions of laronidase for at least 6 months.
      The response from the US FDA is anticipated during the H1 of 2003. Both companies
      plan to initiate two new clinical trials in patients with MPS-I. One study will
      enrol patients with MPS-I under 5 years old. Another study will investigate
      laronidase in patients with advanced clinical symptoms of MPS-I. Additionally,
      patients from the ongoing Phase III study will continue to receive treatment with
      laronidase. On 1 March 2002, BioMarin and Genzyme filed a marketing approval
      application with European regulatory authorities for AldurazymeOE for the
      treatment of MPS-I. Mucopolysaccharidosis I is a rare autosomal recessive
      lysosomal storage disorder caused by alpha-L-iduronidase deficiency. Its
      manifestations in children can include growth and developmental delay,
      enlargement of spleen and liver, skeletal deformity, cardiac and pulmonary
      impairment, vision or hearing loss and mental dysfunction. At present, bone
      marrow transplantation is the only available treatment.

PMID- 12196046
TI  - LeuTech.
AB  - LeuTech is a sterile, lyophilised kit-packaged diagnostic system containing
      murine anti-CD15 IgM monoclonal antibody proprietary radiolabelled with
      technetium 99m ((99m) Tc) for infection imaging. After intravenous injection of
      LeuTech, diagnostic imaging can be obtained within 1h with conventional planar
      gamma camera techniques. LeuTech binds to neutrophils in vivo at the infection
      site. LeuTech is a fast (1h to obtain image), convenient (one-step injection),
      safe, effective (bright, clear images) and cost-effective diagnostic for existing
      and new nuclear imaging markets including chronic and acute indications such as
      appendicitis, ischaemic bowel, post-surgical infection and nosocomial infection.
      Palatin Technologies has successfully completed a Phase III trial with LeuTech in
      203 patients at 10 sites in the USA for the detection of equivocal appendicitis.
      A BLA with the US FDA for LeuTech has been filed for the diagnosis of equivocal
      appendicitis. The US FDA has recommended LeuTech for approval for the diagnosis
      of appendicitis in patients with equivocal signs and symptoms. On 28 September
      2000 Palatin received a 'complete review' letter from the FDA regarding the BLA
      for LeuTech. While, there were no further data requested on the safety and
      clinical efficacy of LeuTech, FDA requested some manufacturing, quality control
      and validation steps and data to be completed prior the approval of LeuTech.
      Palatin plans to finalise the amendments to BLA in the H2 of 2002. LeuTech is
      also being investigated in Phase II clinical trials for the diagnosis of
      osteomyelitis in 45 patients at four sites. Positive interim results from a Phase
      II clinical study conducted in 19 patients with diabetic foot ulcers and
      suspected osteomyelitis were announced at the Society of Nuclear Medicine Annual
      Meeting, Toronto, Canada, in June 2001. Imaging with LeuTech provided a
      diagnostic image within 1 hour compared with the 24 hours required to obtain an
      image using standard-of-care diagnostic, Indium oxide-labelled white blood cells.
      Walter Reed Army Medical Center is evaluating LeuTech for early detection of
      inhalation anthrax. LeuTech is planned to be evaluated for the detection of
      osteomyelitis secondary to joint replacements (such as hip replacement),
      postoperative abscesses, ulcerative colitis and other intra-abdominal infections
      (colitis, spleen or urinary tract). Palatin Technologies has exclusive rights to
      murine anti-CD15 IgM monoclonal antibody from The Wistar Institute of Biology and
      Anatomy. LeuTech has been licensed to Mallinckrodt worldwide, except for Europe.
      In October 2000, Mallinckrodt was acquired by Tyco International. On 15 May 2002,
      Palatin Technologies announced that its agreement with
      Tyco/Healthcare/Mallinckrodt regarding LeuTech marketing was amended to require
      Mallinckrodt to pay an additional $3.2 million to cover half of Palatin's
      expenses for the completion of the FDA's review. The additional funding is
      conditional upon reaching of certain milestones with Palatin receiving $800,000
      within ten days of the signing of the amendment. Under the terms of the original
      agreement (1999), Palatin received a licensing fee of $500,000 and $13 million
      for the stock. All expenses prior to FDA approval were equally shared. Palatin
      will manufacture LeuTech and will receive a transfer price per unit and also
      royalties on net sales.

PMID- 12196047
TI  - Hospital admissions resulting from preventable adverse drug reactions.
AB  - BACKGROUND: Adverse drug reactions (ADRs) are a significant cause of hospital
      admissions. These events can lead to significant morbidity and mortality and
      financial costs. ADRs that may be preventable might be considered a form of
      medication error. OBJECTIVE: To assess the potential preventability of ADRs
      directly related to a patient's hospital admission. METHODS: A retrospective
      chart review of 437 ADRs occurring during an 11-month period was conducted at a
      university hospital. A subset of these events leading to hospital admissions was
      identified for further review. Those that resulted in admission were further
      examined to determine probability of causality, severity, and preventability.
      RESULTS: Over 11 months, 158 ADRs were directly related to hospital admission.
      The relationship of these admissions to drug exposure was determined to be
      probable or highly probable in 154 (97.4%) of these cases. From this group, 96
      (62.3%) of these events were considered potentially preventable, with 23 (24%)
      considered severe to life-threatening. Characteristics associated with these ADRs
      included documentation of a toxic drug concentration or abnormal laboratory value
      (80%), inadequate monitoring of a patient's drug therapy (67%), inappropriate
      dose (51%), patient noncompliance (33%), drug-drug interaction (26%),
      contraindication to therapy (3%), and documented allergy (1%). These ADRs
      resulted in 595 hospital days, with an average length of stay of 6.1 days.
      CONCLUSIONS: ADRs leading to hospital admissions are often preventable.
      Approximately 25% of these events were serious to life-threatening. Most resulted
      from inadequate monitoring of therapy or inappropriate dosing. Patient
      noncompliance and drug interactions were also common causes. Multidisciplinary
      prevention strategies among physicians, pharmacists, other healthcare
      professionals, and patients focusing on communication and education should be
      targeted.

PMID- 12196048
TI  - Intrathecal morphine after cardiac surgery.
AB  - OBJECTIVE: To assess whether intrathecal (IT) analgesia facilitates early
      extubation and provides superior pain control after cardiac surgery compared with
      patient-controlled analgesia (PCA) or nurse-administered SC injections. METHODS:
      Sixty-two patients undergoing elective cardiac surgery participated in this
      prospective, randomized, partly-blinded study. Perioperative care was
      standardized, and patients were assigned to receive IT morphine (ITM group)
      followed by PCA, IT placebo (ITP group) followed by PCA, or SC injections of
      morphine every 4 hours as needed (SC group). Rating scales and questionnaires
      were used to assess clinical outcomes. RESULTS: ITM did not favor earlier
      extubation, and there was even a tendency for longer extubation times in the ITM
      group compared with the ITP and SC groups. Pain scores, adverse effects,
      postoperative recovery, and patient satisfaction were also comparable in the 3
      groups. CONCLUSIONS: Considering that the administration of IT morphine is more
      costly and can be riskier than conventional analgesic regimens, we conclude that
      its use is not indicated in patients undergoing cardiac surgery if early
      extubation is planned.

PMID- 12196050
TI  - Low-molecular-weight heparins and thrombocytosis.
AB  - BACKGROUND: A possible association between low-molecular-weight heparins (LMWHs)
      and thrombocytosis was suspected from spontaneous reports to the French
      Pharmacovigilance System. This association is not mentioned in LMWH's summary of
      product characteristics. METHODS: All case records in the French
      Pharmacovigilance database were reanalyzed for relevance and causality, and the
      case/noncase approach was used including reports of thrombocytosis as cases and
      all other reports as noncases. RESULTS: Fifty-one patients treated with LMWHs had
      platelet counts >500 x 10(3)/mm(3). All patients were asymptomatic, and 1 had a
      positive rechallenge. There were 143 cases of thrombocytosis among the 174 213
      reports in the database, with 61 of 4644 involving LMWHs. The calculated relative
      reporting ratio is 27.5 (p < 0.0001; 95% CI 19.5 to 38.9). CONCLUSIONS: There is
      a highly significant association of thrombocytosis reported with LMWH treatment.

PMID- 12196049
TI  - Pharmacodynamics of high-dose methotrexate in pediatric patients.
AB  - OBJECTIVE: To establish a relationship between the pharmacokinetics of high-dose
      methotrexate (MTX) and toxicity in children of a pediatric oncology department
      and to reassess MTX concentrations at which the patients would be at high risk
      for toxic effects. METHODS: This study included 37 patients (227 treatment
      courses) who received a median dose of 4.87 g/m(2) of MTX in a 4-hour infusion.
      The population pharmacokinetic parameters of MTX were estimated by parametric
      (IT2B) and nonparametric methods (NPEM). Gastrointestinal, renal, and hematologic
      toxicity were evaluated. The relationship between pharmacokinetic parameters and
      toxicity was analyzed by logistic regression and multiple linear regression.
      RESULTS: Equations to predict hematologic and nonhematologic toxicity were
      obtained. An increase of 100 micro mol/L in the MTX peak concentration meant a
      12% (p = 0.03) higher risk of vomiting; a significant delay in MTX elimination
      implied a 5.76-fold higher risk of mucositis (p < 0.001). An increase of 1 micro
      mol/L in the MTX concentration 24 hours after the end of the infusion (Cp(24h))
      led to a 43% increase in the risk of renal toxicity (p < 0.001). Hematologic
      toxicity was significantly conditioned by the baseline leukocyte count and
      Cp(24h) (p < 0.001). CONCLUSIONS: The analysis of high-dose MTX
      pharmacokinetic/pharmacodynamic relationship to toxicity has led to equations
      able to predict toxicity that are easily applicable to daily practice. Cp(24h)
      >3.5 micro mol/L was confirmed as an indicator of high risk of toxicity.

PMID- 12196051
TI  - Effect of enoxaparin on homocysteine concentration in warfarin-treated patients.
AB  - BACKGROUND: Elevated plasma total homocysteine (tHcy) concentration is an
      emerging independent risk factor for hypercoagulability states and cardiovascular
      diseases. Many disease states and various drug treatment regimens are known to
      affect plasma tHcy concentration. OBJECTIVE: To examine the effect of short-term
      treatment with the low-molecular-weight heparin enoxaparin on plasma tHcy
      concentrations. METHODS: A prospective study was conducted in an outpatient
      anticoagulation clinic set in a tertiary care referral medical center. Subjects
      included twenty-four consecutive patients treated with warfarin who were
      scheduled for short-term enoxaparin treatment. Fasting plasma tHcy concentrations
      were measured before and after 3 days of enoxaparin treatment in patients who
      began short-term therapy with enoxaparin because of temporary inadequate
      anticoagulation (international normalized ratio <1.5). The main outcome measures
      were the difference in tHcy concentration between baseline and after enoxaparin
      treatment. RESULTS: tHcy plasma concentrations decreased in most patients (n =
      21), did not change in 2, and increased in 1 patient after 3 days of enoxaparin
      treatment. The decline of tHcy was statistically significant: from 9.8 +/- 3.4 to
      7.6 +/- 2.6 micro mol/L (mean +/- SD; p < 0.005). This decline was more prominent
      in patients with baseline tHcy plasma concentrations above the normal range
      compared with patients with normal baseline concentrations. Six patients in whom
      a third sample was obtained 15-30 days after the last enoxaparin injection
      developed decreased mean tHcy plasma concentrations: from 9.1 +/- 3.0 micro mol/L
      at baseline to 6.4 +/- 2.0 micro mol/L on day 3 and further to 5.7 +/- 1.8 micro
      mol/L on days 15-30. No relation was found between age, gender, treatment
      indication, and average weekly dose of warfarin to the presence or magnitude of
      tHcy plasma concentration decline. CONCLUSIONS: Short-term treatment with
      enoxaparin reduces plasma tHcy concentrations. Further studies are needed to
      clarify the mechanism and the clinical significance of enoxaparin's effect.

PMID- 12196052
TI  - Empiric carbapenem monotherapy in pediatric bone marrow transplant recipients.
AB  - OBJECTIVE: To determine which carbapenem (imipenem/cilastatin or meropenem) was
      the preferable empiric antibiotic monotherapy in pre-engrafted pediatric bone
      marrow transplant (BMT) patients in terms of patient tolerance, therapeutic
      efficacy, and cost. METHODS: We prospectively analyzed 16 pediatric BMT patients
      who received meropenem, and retrospectively analyzed 16 matched patients who had
      received imipenem/cilastatin for BMT procedures during the prior 2-year period.
      We evaluated the patients for evidence of bacterial infection, necessity for
      concurrent antibiotics, vomiting episodes, duration of concurrent total
      parenteral nutrition (TPN), and cost of therapy. RESULTS: We found no differences
      in the number of culture proven or clinically suspected breakthrough bacterial
      infections or the need for concurrent additional antibiotics between the groups.
      Our analysis found that patients who received meropenem experienced significantly
      less vomiting than those in the imipenem/cilastatin cohort. Our data showed both
      direct and indirect cost savings for the meropenem group. The statistical and
      clinical differences in the number of vomiting episodes between these groups
      impacted other aspects of patient care, antiemetic use, and TPN duration.
      CONCLUSIONS: By switching to meropenem, we reduced the cost of antiemetic therapy
      per patient treatment course, and also showed a trend toward reduced duration of
      TPN. We found that meropenem provided both clinical and fiscal advantages over
      imipenem/cilastatin as empiric antibiotic monotherapy in neutropenic pediatric
      BMT patients.

PMID- 12196054
TI  - Increased use of antidepressants in Canada: 1981-2000.
AB  - OBJECTIVE: To provide a descriptive analysis of Canadian utilization
      (prescriptions, cost, cost per prescription) of antidepressants (ATC-code: N06A).
      METHODS: IMS Canada provided prescription volumes and costs from 1981 to 2000. We
      analyzed time trends for antidepressants in general and 4 subclasses (tricyclic
      antidepressants [TCAs], selective serotonin-reuptake inhibitors [SSRIs], dual
      action antidepressants [DAAs], and monoamine oxidase inhibitors [MAOIs]). Costs
      were discounted using the consumer price index, adjusting for population growth
      using data from Statistics Canada. RESULTS: Between 1981 and 2000, total
      prescriptions increased from 3.2 to 14.5 million. Market share of TCAs (23.7%)
      and MAOIs (2.1%) remained constant, despite the introduction of the first SSRI,
      fluoxetine, in 1989. SSRI prescriptions increased to 6.7 million (market share
      46.3%). DAA use increased gradually after 1994 to 3.5 million prescriptions
      (23.9% market share) in 2000. The number of prescriptions expanded (possibly due
      to SSRIs) by 238%, with an increased cost of 2.7 billion dollars. Total
      expenditures for antidepressants increased exponentially, from 31.4 million
      dollars in 1981 to 543.4 million dollars in 2000 (y = 4E - 130e(0.1556x) [R(2) =
      0.99]). Cost per prescription increased linearly from 9.85 dollars in 1981 to
      37.44 dollars in 2000 (y = 1.72x + 7.92 [R(2) = 0.96]). CONCLUSIONS: Utilization
      and costs of pharmacotherapy for depression have increased above the inflation
      rate and are expected to exceed 1.2 billion dollars (50 dollars per prescription)
      in 2005. Increased costs may be due to increased availability of new products
      with increased safety, efficacy, and acquisition cost; increased number of users;
      and increasing costs.

PMID- 12196053
TI  - Single-patient drug trial methodology for allergic rhinitis.
AB  - BACKGROUND: Historically, single-patient trials (SPTs) have been specifically
      designed for each patient, requiring significant time and effort for execution.
      There has been no previous attempt to standardize an SPT for routine commercial
      availability. OBJECTIVE: To validate the use of an SPT method to discriminate
      effectiveness and adverse events while comparing drugs/doses in patients with
      allergic rhinitis. DESIGN: Double-blind, randomized, 4 paired-period, multiple
      crossover SPT. SETTING: Academic and commercial investigative sites. PATIENTS:
      Thirty-six patients with allergic rhinitis were evaluated for the most
      appropriate treatment; 6 of these participated in 2 different SPTs.
      INTERVENTIONS: Treatment of symptoms of allergic rhinitis by comparing either
      loratadine with chlorpheniramine maleate or loratadine with placebo in a series
      of SPTs. MEASUREMENTS: Effectiveness endpoints were selected from a modern, Food
      and Drug Administration (FDA)-approved new drug application. Expected adverse
      events were directly solicited; unsolicited events were also recorded. Total
      signs and symptoms cumulatively included sneezing, runny nose, itchy nose, teary
      eyes, and itchy eyes. Quality of life was measured by the most bothersome symptom
      and the patient's global evaluation. RESULTS: Of 42 initiated SPTs, 40 (95%)
      provided complete data and 1 (2%) provided partial data, resulting in 41 (98%)
      evaluable tests. Thirty-one evaluable SPTs compared loratadine 10 mg/d with
      chlorpheniramine maleate 12 mg twice daily, and 10 SPTs compared loratadine 10
      mg/d with placebo. Four of 31 SPTs (13%) showed significant superiority for
      loratadine over chlorpheniramine maleate and 5 of 31 (16%) for chlorpheniramine
      maleate over loratadine. Twenty-two of 31 (71%) showed parity performance between
      loratadine and chlorpheniramine maleate. Loratadine was significantly superior to
      placebo in 3 of 10 trials (30%), consistent with rates found in 3 pivotal group
      trials used for FDA approval (24%, 17%, and 0%). Sleepiness could be
      discriminated for loratadine versus placebo and for chlorpheniramine maleate
      versus loratadine. CONCLUSIONS: The allergic rhinitis SPT proved to be acceptable
      to patients, feasible to administer, and reproducible. It can statistically
      discriminate effectiveness and adverse events, serving as a useful, prognostic
      tool in community practice.

PMID- 12196055
TI  - Nephrotoxicity and purpura associated with levofloxacin.
AB  - OBJECTIVE: To report a patient with lung cancer and idiopathic myelofibrosis with
      myeloid metaplasia who developed purpura and acute renal failure while receiving
      levofloxacin, and review the existing literature on quinolone nephrotoxicity.
      CASE SUMMARY: A 73-year-old white man, with a medical history of non-small-cell
      lung cancer and idiopathic myelofibrosis with myeloid metaplasia, was prescribed
      levofloxacin because of a lower urinary tract infection. Three days later, he
      presented with palpable purpura and erythematous skin lesions over the lower
      limbs and trunk, with a markedly reduced urinary output. Serum creatinine and
      urea nitrogen were 6.4 and 190 mg/dL, respectively. Levofloxacin was
      discontinued, and prednisone, furosemide, and intravenous fluids were given. The
      patient fully recovered over the ensuing 4 weeks. CONCLUSIONS: Nephrotoxicity
      associated with levofloxacin is uncommon. Allergic interstitial nephritis or
      vasculitis is believed to be the underlying pathologic process. Definitive
      diagnosis requires performance of renal biopsy, although this is not always
      feasible. In this case, a return of renal function to normal, with the
      disappearance of purpura following the discontinuation of levofloxacin and
      corticosteroid treatment, supports the presumptive diagnosis of a
      hypersensitivity reaction to levofloxacin.

PMID- 12196056
TI  - Treatment of azole-resistant oropharyngeal candidiasis with topical amphotericin
      B.
AB  - OBJECTIVE: To report a case of successful treatment of azole-refractory
      oropharyngeal candidiasis with topical amphotericin B. CASE SUMMARY: A 30-year
      old white woman presented with recurrent oral thrush. The patient had been
      exposed to azole antifungals for >20 years, and in vitro susceptibility tests
      revealed class resistance. The patient started taking amphotericin B 100 mg oral
      suspension swish-and-spit 4 times daily. After 4 weeks of topical amphotericin B
      treatment, the patient reported significant symptomatic improvement. The oral
      candidiasis worsened following a course of oral antibiotics, but improved once
      the antibiotic was discontinued and after receiving amphotericin B swish-and
      swallow for 4 additional weeks. DISCUSSION: Current Infectious Diseases Society
      of America guidelines include topical amphotericin B as a potentially effective
      option for the treatment of oropharyngeal candidiasis. There is limited evidence
      to support this recommendation. Besides lack of data, an appropriate dosing
      regimen and consistent means of product formulation need to be determined.
      CONCLUSIONS: This report demonstrates the potential role for topical amphotericin
      B in the treatment of azole-refractory oral candidiasis. Double-blind,
      randomized, controlled trials are needed to define dosing, efficacy,
      administration, and long-term safety of oral amphotericin B.

PMID- 12196057
TI  - Metoclopramide-induced supersensitivity psychosis.
AB  - OBJECTIVE: To report 2 cases of metoclopramide-induced supersensitivity
      psychosis. CASE SUMMARIES: A 74-year-old Taiwanese man was treated with
      metoclopramide 5 mg 4 times daily for 6 months. A second patient, a 65-year-old
      Taiwanese man, was treated with metoclopramide 5 mg 4 times daily for 3 months.
      After discontinuation of metoclopramide, both patients developed hallucinatory
      experiences and delusions. DISCUSSION: This is the first report of metoclopramide
      induced supersensitivity psychosis. Chronic administration of a dopamine
      antagonist (e.g., metoclopramide) might induce dopamine receptor
      supersensitivity. It is hypothesized that exacerbation or occurrence of psychotic
      symptoms following neuroleptic withdrawal results from mesolimbic dopamine
      supersensitivity. CONCLUSIONS: The complications of long-term metoclopramide
      therapy should be seriously considered when the treatment regimens are being
      planned. Clinicians should attempt to treat patients with the lowest effective
      dosage of medication for the briefest therapeutic period to minimize the risks of
      adverse reactions.

PMID- 12196058
TI  - Delayed wound healing with sirolimus after liver transplant.
AB  - OBJECTIVE: To report 3 separate cases of wound dehiscence in liver transplant
      recipients receiving sirolimus for immunosuppressive therapy. CASE SUMMARIES:
      Three patients who had received liver transplants experienced a delay in wound
      granulation and healing after being placed on an immunosuppressive regimen
      containing sirolimus and steroids. Each patient was admitted and treated for
      wound dehiscence, at which time sirolimus was discontinued. When other
      immunosuppressive agents were substituted for sirolimus, each incisional wound
      granulated and closed without complication. DISCUSSION: Sirolimus is an important
      adjunctive immunosuppressant used to prevent acute rejection episodes in patients
      who have undergone transplant, particularly when nephrotoxic effects from first
      line calcineurin inhibitors become problematic. The unique ability of sirolimus
      to inhibit smooth muscle cell proliferation and intimal thickening by blocking
      important growth factors may subsequently become a significant feature to prevent
      the development of chronic rejection. Theoretically, by this same mechanism,
      sirolimus may play a role in forestalling wound healing and may even promote
      dehiscence. CONCLUSIONS: These case reports describe patients who underwent liver
      transplant who developed wound dehiscence possibly secondary to sirolimus
      therapy. Although the cases were complicated by acute rejection, wound
      infections, and comorbidities, wound granulation and healing began after
      discontinuation of sirolimus. Substitution with another immunosuppressant may be
      necessary for patients who experience wound dehiscence after transplant.

PMID- 12196059
TI  - Clonidine-induced hypertension in a patient with a spinal lesion.
AB  - OBJECTIVE: To report a case of possible clonidine-induced hypertension (by
      Naranjo score) in a patient with a C4 spinal lesion. BACKGROUND: Clonidine is a
      medication long used to treat hypertension, and it is still used in the treatment
      of refractory hypertension. Although effective, clonidine use is hindered by
      adverse effects and its dual mechanism of action. CASE SUMMARY: A 39-year-old
      white, quadriplegic man with poorly controlled pain displayed many
      characteristics consistent with autonomic dysfunction (e.g., C4 spinal lesion,
      orthostatic hypotension, hypertension). The patient was routinely receiving
      transdermal clonidine and also received transdermal nitroglycerin paste as needed
      for control of acute hypertensive episodes. On the recommendation of the home
      healthcare pharmacists, clonidine was discontinued. Since that time, the
      patient's blood pressure and the use of emergent antihypertensive treatment have
      decreased significantly (maximum systolic and diastolic BP by approximately 50
      and 25 mm Hg, respectively). CONCLUSIONS: Many of the characteristics of
      autonomic dysfunction, such as refractory hypertension, can seem selective for
      the use of clonidine and, because of its reliance on central alpha(2)-activity
      for its hypotensive effects, clonidine may induce hypertension in patients with
      autonomic dysfunction. Clonidine should be used with great caution when autonomic
      dysfunction is suspected.

PMID- 12196060
TI  - Phenytoin/isradipine interaction causing severe neurologic toxicity.
AB  - OBJECTIVE: To report a young man on phenytoin who developed acute neurologic
      symptoms after isradipine was introduced to his treatment regimen and discuss the
      possible causes of this drug interaction. CASE SUMMARY: A 21-year-old white man,
      with propionic acidemia and seizures treated with phenytoin and carbamazepine,
      was started on isradipine for essential hypertension. Soon thereafter, he
      developed acute and severe lethargy, ataxia, dysarthria, and weakness that
      resolved once isradipine was withheld. Phenytoin concentrations were within
      normal limits or elevated, despite sequential reductions of phenytoin dosage,
      during concomitant isradipine administration. DISCUSSION: Isradipine is a known
      inhibitor of the CYP450 isoenzyme family. Although the daily dose of phenytoin
      was decreased significantly, phenytoin blood concentrations remained high,
      suggesting a pharmacokinetic interaction. Previously, the patient had never had
      neurologic symptoms associated with increased phenytoin concentrations. This also
      indicates a likely pharmacodynamic interaction between phenytoin and the calcium
      channel blocker. Both phenytoin and isradipine have been shown to bind to calcium
      channels and to inhibit calcium entry into the cells. Binding of isradipine to
      the brain has been described in humans and animals, and calcium-channel blockers
      have been shown to cause potentiation of anticonvulsant action of phenytoin.
      CONCLUSIONS: Acute pharmacokinetic and pharmacodynamic interactions between
      phenytoin and isradipine were probably responsible for the lethargy, dysarthria,
      ataxia, and weakness our patient developed. The combination of phenytoin and
      calcium-channel blockers should be used with caution.

PMID- 12196061
TI  - Conjugated heptavalent pneumococcal vaccine.
AB  - OBJECTIVE: To review the immunogenicity, efficacy, and safety of the heptavalent
      conjugated pneumococcal vaccine (PCV7). DATA SOURCES: A MEDLINE search (1993
      August 2001) of research limited to humans published in the English language was
      conducted. STUDY SELECTION: Findings from randomized, controlled, multicenter
      trials were reviewed. Literature regarding epidemiology, control, and treatment
      of invasive pneumococcal diseases in different populations and the Advisory
      Committee on Immunization Practices recommendations were also reviewed. DATA
      SYNTHESIS: PCV7 administered to infants aged 2, 4, and 6 months, with a booster
      dose at 12-15 months, has been shown to be immunogenic. It decreases the
      incidence of invasive pneumococcal disease; individual data on bacteremia and
      meningitis are unavailable. Findings from clinical trials showed that invasive
      pneumococcal disease caused by vaccine serotypes was reduced by 87%, 58%, and 62%
      for children <1 year, <2 years, and <5 years of age, respectively, after
      introduction of routine vaccine use. The overall incidence of acute otitis media
      did not decrease significantly. However, culture-confirmed episodes and episodes
      due to pneumococcal serotypes included in the vaccine were reduced. The vaccine
      was immunogenic in children with sickle cell disease, but its efficacy in
      preventing invasive pneumococcal diseases remains unclear. Although
      immunogenicity and efficacy trials are lacking, the vaccine is recommended for
      Alaskan Native or American Indian children between 24 and 59 months of age, and
      for children with underlying conditions such as HIV infection, AIDS, other
      immunocompromising conditions, and chronic illnesses. At the manufacturer's list
      price of 58 dollars/dose, PCV7 is not projected to be cost-effective after 4
      doses. Postmarketing analysis evaluating immunogenicity and efficacy in the
      excluded population may favorably change this. CONCLUSIONS: Based on published
      efficacy and immunogenicity data, pharmacy formularies should include PCV7.

PMID- 12196062
TI  - Current and emerging therapy for primary pulmonary hypertension.
AB  - OBJECTIVE: To review the epidemiology, pathophysiology, clinical symptoms, and
      diagnostic workup of primary pulmonary hypertension (PPH) and to discuss the
      available data on the current and emerging therapies being used to treat this
      disorder. DATA SOURCES: Primary and review articles were identified with a
      MEDLINE search (1966-December 2001) and through secondary sources. STUDY
      SELECTION AND DATA EXTRACTION: All articles identified from the data sources were
      evaluated and all information deemed relevant was included in this review. DATA
      SYNTHESIS: In the absence of a definable cause, PPH is a disorder classified by a
      progressive increase in pulmonary vascular resistance and mean pulmonary artery
      pressure. A relatively rare condition, PPH has an annual incidence of 1-2 cases
      per million people, slightly higher in women than men. The prognosis is poor,
      with a mean survival time of 2.8 years after diagnosis if untreated.
      Vasoconstriction, vascular remodeling, and thrombosis are hallmarks of the
      disease process. Anticoagulation and vasodilators are the most commonly employed
      treatment options, showing benefits in clinical outcomes, hemodynamic parameters,
      and mortality. Several new vasodilators are being evaluated for the treatment of
      PPH. Bosentan was recently approved as the first oral agent for the treatment of
      PPH. Iloprost, treprostinil, and beraprost are investigational agents in Phase
      III studies. CONCLUSIONS: Until additional studies and experience with these
      agents become available, calcium-channel blockers (CCBs) remain the first option
      for therapy. For patients not responding to CCBs, therapeutic options will now
      include epoprostenol and bosentan. Since there are no comparison trials between
      these 2 agents, therapeutic decisions should be based on patient-specific
      concerns. Clinical data and experience support the use of epoprostenol; however,
      in patients at risk or considered unsuitable candidates, bosentan may become a
      preferred option. Additional studies are warranted to address the potential
      therapeutic benefits of combination therapy and long-term benefits of agents to
      treat PPH.

PMID- 12196063
TI  - Recombinant human activated protein C for use in severe sepsis.
AB  - OBJECTIVE: To review the efficacy and safety of drotrecogin alfa (recombinant
      human activated protein C) in the treatment of sepsis. DATA SOURCES: Literature
      was identified through a MEDLINE search (1966-January 2002), the product
      manufacturer, and the Food and Drug Administration. STUDY SELECTION/DATA
      EXTRACTION: All relevant information identified from the data sources was
      evaluated. DATA SYNTHESIS: Drotrecogin alfa reduces coagulation and inflammation
      in septic patients. A large placebo-controlled clinical trial (n = 1690) of
      drotrecogin alfa in severely septic patients demonstrated a reduction in
      mortality (24.7% vs. 30.8%; p = 0.005), with increased bleeding risks (24.9% vs.
      17.7%; p <0.001). Patients with more severe sepsis appeared to gain the most
      benefit. The complete clinical and economic impact of this agent requires further
      analysis. CONCLUSIONS: Drotrecogin alfa offers a significant advance in the
      treatment of severe sepsis. Judicious use in appropriate patients is necessary to
      control cost and maximize clinical benefits.

PMID- 12196064
TI  - Acute renal failure in hospitalized patients: part II.
AB  - BACKGROUND: Acute renal failure (ARF) is a common condition in hospitalized
      patients. Research has been unable to identify the optimal target for therapeutic
      intervention; hence, effective prevention of and/or treatment for ARF remain
      elusive. OBJECTIVE: To examine the usefulness of current and potential
      pharmacologic treatments in seriously ill, hospitalized patients. DATA SOURCES: A
      MEDLINE search (1996-June 2002) was conducted using the search terms kidney (drug
      effects) and acute kidney failure (drug therapy). Bibliographies of selected
      articles were also examined to include all relevant investigations. STUDY
      SELECTION AND DATA EXTRACTION: Review articles, meta-analyses, and clinical
      trials describing prevention of and treatment for hospital-acquired ARF were
      identified. Results from prospective, controlled trials were given priority when
      available. CONCLUSIONS: Appropriate management of ARF includes prospective
      identification of at-risk patients, fluid administration, and optimal hemodynamic
      support. Drug treatments, including low-dose dopamine and diuretics, have
      demonstrated extremely limited benefits and have not been shown to improve
      patient outcome. Experimental agents influence cellular processes of renal
      dysfunction and recovery; unfortunately, relatively few drugs show promise for
      the future.

PMID- 12196065
TI  - Herbs for benign prostatic hyperplasia.
AB  - OBJECTIVE: To review and evaluate the literature relative to the use of herbal
      therapies in the treatment of benign prostatic hyperplasia. DATA SOURCES:
      Literature was identified by MEDLINE, Embase, International Pharmaceutical
      Abstracts, and the International Bibliographic Information on Dietary Supplements
      searches and through cross-referencing of selected articles. STUDY SELECTION/DATA
      EXTRACTION: All articles identified from the data sources were evaluated and all
      information deemed relevant was included in this review. DATA SYNTHESIS: A large
      percentage of men >50 years old begin to experience signs and symptoms of benign
      prostatic hyperplasia (BPH). Herbs hold promise in the treatment of BPH. Serenoa
      repens, Pygeum africanum, Urtica dioica radix, and Cucurbita peponis semen are
      some of the botanical therapies used in the treatment of BPH. CONCLUSIONS: There
      are many European studies examining efficacy, dose, and adverse effects of these
      plants in the treatment of BPH. However, numerous questions remain. These include
      issues concerning long-term beneficial and adverse effects of herbal therapy,
      prevention of complications, standardization of extracts, and concomitant use
      with "mainstream" medications. Based on the information available today, these
      botanical therapies can be used for treatment of a number of objective and
      subjective symptoms in patients with BPH, stages I and II.

PMID- 12196066
TI  - Propofol infusion syndrome in critically ill patients.
AB  - OBJECTIVE: To describe the clinical presentation of propofol infusion syndrome in
      critically ill adults. DATA SOURCES: Clinical literature was accessed through
      MEDLINE (1966 - March 2001). Key search terms included Diprivan, propofol, and
      propofol infusion syndrome. Case reports and small case series evaluating the use
      and toxicity of propofol in sedating critically ill adults were reviewed. DATA
      SYNTHESIS: The association between propofol infusion syndrome and death in
      children secondary to myocardial failure is well documented. However, few data
      are available regarding the syndrome in critically ill adults. Based on a review
      of those data, it appears that propofol infusion syndrome can occur in both
      children and adults. Common clinical features of propofol infusion syndrome may
      include hyperkalemia, hepatomegaly, lipemia, metabolic acidosis, myocardial
      failure, and rhabdomyolysis. Although the premise has not been proven, recent
      published cases appear to demonstrate an association between propofol infusion
      and death secondary to myocardial failure. CONCLUSIONS: Until further safety data
      become available, caution should be exercised when using high-dose (>5 mg/kg/h)
      and long-term (>48 h) propofol infusion in sedating critically ill adults.

PMID- 12196067
TI  - Leukotriene modifiers to prevent aspirin-provoked respiratory reactions in
      asthmatics.
AB  - OBJECTIVE: To evaluate the use of leukotriene modifiers in preventing aspirin
      provoked respiratory reactions in asthmatics. DATA SOURCES: Clinical literature
      accessed through MEDLINE (1965-February 2001). Key search terms included aspirin,
      asthma, leukotriene, and treatment. DATA SYNTHESIS: Aspirin-sensitive asthmatics
      experience a wide variety of symptoms, ranging from rhinitis to life-threatening
      bronchospasms, after the ingestion of aspirin or nonsteroidal antiinflammatory
      drugs (NSAIDs). The relationship between aspirin sensitivity, asthma, and nasal
      polyps was first reported in 1922. The exact mechanism of these reactions is not
      clearly understood. Four studies investigated the use of leukotriene modifiers to
      prevent aspirin-provoked respiratory reactions. The efficacy of these agents
      ranged from complete inhibition to no blockade. CONCLUSIONS: Patients who
      experience aspirin-sensitive asthma should be cautious when taking aspirin and
      NSAIDs, despite treatment with leukotriene inhibitors.

PMID- 12196068
TI  - Treatment of itching associated with intrahepatic cholestasis of pregnancy.
AB  - OBJECTIVE: To review the drug therapy for the treatment of itching associated
      with intrahepatic cholestasis of pregnancy (ICP). DATA SOURCES: A comprehensive
      literature search was conducted in MEDLINE (1966-July 2002) using the following
      MeSH terms: pregnancy, itching, intrahepatic cholestasis, cholestyramine,
      ursodeoxycholic acid, and phenobarbital. Current Contents (1966-July 2002),
      International Pharmaceutical Abstracts (1970-June 2002), and Cochrane Database
      were also searched using those terms. Web of Science search was used to search
      references found in articles. DATA SYNTHESIS: Eight clinical trials and several
      observational studies were identified evaluating the safety and efficacy of
      ursodeoxycholic acid (UDCA) in the treatment of ICP. Although these studies were
      small and inconsistent, improvement in maternal and fetal morbidity was
      demonstrated. Observational studies suggest that cholestyramine may be associated
      with improved maternal morbidity without a documented improvement in fetal
      outcome. Two observational studies evaluated the efficacy of phenobarbital for
      ICP treatment. Phenobarbital use was not associated with improved maternal or
      fetal morbidity/mortality. CONCLUSIONS: Data from large, well-designed,
      randomized, controlled trials of treatment of ICP are lacking. Data that are
      available support the use of UDCA as a first-line agent and cholestyramine as a
      second-line agent for treatment of ICP. There is little evidence to recommend
      phenobarbital in the treatment of itching associated with that condition.

PMID- 12196070
TI  - Ranking of US pharmacy schools based on perception, funding, and publications.

PMID- 12196069
TI  - Role of N-acetylcysteine in the prevention of radiocontrast-induced nephropathy.
AB  - OBJECTIVE: To examine the role of N-acetylcysteine (NAC) in the prevention of
      radiocontrast-induced nephropathy (RIN). DATA SOURCES: A literature search of
      MEDLINE (1966-December 2001) was performed using the following search terms: N
      acetylcysteine, nephropathy, acute renal failure, and radiocontrast. STUDY
      SELECTION: Pertinent English-language animal and human studies were reviewed.
      DATA SYNTHESIS: Few small animal trials have demonstrated that NAC significantly
      prevents the development or reduces the severity of acute renal failure. Two
      human studies demonstrated NAC significantly reduces the occurrence of RIN.
      CONCLUSIONS: NAC may reduce the occurrence of RIN in high-risk patients. Further
      large-scale studies are needed to corroborate findings from earlier trials.

PMID- 12196071
TI  - Measurement of occupational adjustment in pharmacy: is it important?

PMID- 12196072
TI  - Enoxaparin safety in patients with severe thrombocytopenia.

PMID- 12196073
TI  - Effects of mycophenolate mofetil on hematocrit after renal transplantation.

PMID- 12196074
TI  - Anaphylactic reaction to liposomal amphotericin B.

PMID- 12196075
TI  - Comment: hepatotoxicity associated with chronic acetaminophen administration in
      patients without risk factors.

PMID- 12196076
TI  - Comment: treatment of heparin-induced thrombocytopenia.

PMID- 12196077
TI  - The potential role of fondaparinux as venous thromboembolism prophylaxis after
      total hip or knee replacement or hip fracture surgery.

PMID- 12196078
TI  - Unforeseen consequences of terrorism: medically unexplained symptoms in a time of
      fear.

PMID- 12196079
TI  - Effectiveness of interventions to prevent sexually transmitted infections and
      human immunodeficiency virus in heterosexual men: a systematic review.
AB  - Our objective was to review systematically studies of interventions to prevent
      transmission of sexually transmitted infections (STIs) and human immunodeficiency
      virus (HIV) in heterosexual men. Of 1157 studies identified through database and
      hand searching, 27 met our inclusion criteria. Most interventions targeted
      specific groups of men (eg, those attending STI clinics) rather than general
      populations. Few were conducted with men alone, and most focused on behavioral
      and social psychological rather than morbidity outcomes. Of 8 interventions
      designed to reduce STI incidence (including HIV), 5 were successful, 2 were
      unsuccessful, and 1 had equivocal results. Of the 5 successful interventions, 1
      was carried out in the workplace, 1 in the military, and 3 in STI clinics.They
      included on-site individual counseling and HIV testing, mass communications
      regarding risk reduction, and multiple-component motivation and skills education
      in STI clinics. More high-quality research into the effectiveness of
      interventions targeting heterosexual men is needed, especially methodologically
      sound trials to evaluate effects on morbidity.

PMID- 12196081
TI  - Fondaparinux vs enoxaparin for the prevention of venous thromboembolism in major
      orthopedic surgery: a meta-analysis of 4 randomized double-blind studies.
AB  - BACKGROUND: Orthopedic surgery remains a condition at high risk of venous
      thromboembolism (VTE). Fondaparinux, the first of a new class of synthetic
      selective factor Xa inhibitors, may further reduce this risk compared with
      currently available thromboprophylactic treatments. METHODS: A meta-analysis of 4
      multicenter, randomized, double-blind trials in patients undergoing elective hip
      replacement, elective major knee surgery, and surgery for hip fracture (N = 7344)
      was performed to determine whether a subcutaneous 2.5-mg, once-daily regimen of
      fondaparinux sodium starting 6 hours after surgery was more effective and as safe
      as approved enoxaparin regimens in preventing VTE. The primary efficacy outcome
      was VTE up to day 11, defined as deep vein thrombosis detected by mandatory
      bilateral venography or documented symptomatic deep vein thrombosis or pulmonary
      embolism. The primary safety outcome was major bleeding. RESULTS: Fondaparinux
      significantly reduced the incidence of VTE by day 11 (182 [6.8%] of 2682
      patients) compared with enoxaparin (371 [13.7%] of 2703 patients), with a common
      odds reduction of 55.2% (95% confidence interval, 45.8% to 63.1%; P<.001); this
      beneficial effect was consistent across all types of surgery and all subgroups.
      Although major bleeding occurred more frequently in the fondaparinux-treated
      group (P =.008), the incidence of clinically relevant bleeding (leading to death
      or reoperation or occurring in a critical organ) did not differ between groups.
      CONCLUSION: In patients undergoing orthopedic surgery, 2.5 mg of fondaparinux
      sodium once daily, starting 6 hours postoperatively, showed a major benefit over
      enoxaparin, achieving an overall risk reduction of VTE greater than 50% without
      increasing the risk of clinically relevant bleeding.

PMID- 12196082
TI  - Influenza burden of illness: estimates from a national prospective survey of
      household contacts in France.
AB  - BACKGROUND: The burden of influenza among ambulatory patients is still relatively
      unknown, although this knowledge is crucial for evaluating strategies against
      influenza. We estimated the impact of influenza in terms of uncomplicated
      morbidity and its consequences on health care utilization and lost workdays.
      METHODS: A national prospective household contact study between January 4, 2000,
      and March 15, 2000, in France recruited the households of 946 persons who visited
      a physician (index cases); 395 households with influenza-positive index cases
      completed the follow-up, which assessed the clinical impact of influenza, medical
      visits, treatment, and lost workdays in these index cases and their contacts.
      RESULTS: Of 817 assessable household contacts, 313 developed clinical influenza
      (secondary cases); 178 (57%) of them visited a physician at least once
      (consulting secondary cases). The median duration of illness was 8 days (95%
      confidence interval [CI], 7-8 days) in index cases, 7 days (95% CI, 7-8 days) in
      consulting secondary cases, and 4 days (95% CI, 3-5 days) in nonconsulting
      secondary cases (P<.001); the median duration of treatment in these groups was 8
      days (95% CI, 8-9 days), 8 days (95% CI, 7-10 days), and 5 days (95% CI, 4-6
      days), respectively (P<.001); and their mean +/- SD number of lost workdays was
      4.0 +/- 2.8, 2.9 +/- 2.5, and 0.3 +/- 0.6, respectively, in working adults
      (P<.001). CONCLUSIONS: These results confirm the substantial burden of illness of
      influenza. The results should be useful for evaluating the cost-effectiveness of
      strategies against influenza.

PMID- 12196083
TI  - Community-acquired pneumonia due to gram-negative bacteria and pseudomonas
      aeruginosa: incidence, risk, and prognosis.
AB  - BACKGROUND: Initial empirical antimicrobial treatment of patients with community
      acquired pneumonia (CAP) is based on expected microbial patterns. We determined
      the incidence of, prognosis of, and risk factors for CAP due to gram-negative
      bacteria (GNB), including Pseudomonas aeruginosa. METHODS: Consecutive patients
      with CAP hospitalized in our 1000-bed tertiary care university teaching hospital
      were studied prospectively. Independent risk factors for CAP due to GNB and for
      death were identified by means of stepwise logistic regression analysis. RESULTS:
      From January 1, 1997, until December 31, 1998, 559 hospitalized patients with CAP
      were included. Sixty patients (11%) had CAP due to GNB, including P aeruginosa in
      39 (65%). Probable aspiration (odds ratio [OR], 2.3; 95% confidence interval
      [CI], 1.02-5.2; P =.04), previous hospital admission (OR, 3.5; 95% CI, 1.7-7.1;
      P<.001), previous antimicrobial treatment (OR, 1.9; 95% CI, 1.01-3.7; P =.049),
      and the presence of pulmonary comorbidity (OR, 2.8; 95% CI, 1.5-5.5; P =.02) were
      independent predictors of GNB. In a subgroup analysis of P aeruginosa pneumonia,
      pulmonary comorbidity (OR, 5.8; 95% CI, 2.2-15.3; P<.001) and previous hospital
      admission (OR, 3.8; 95% CI, 1.8-8.3; P =.02) were predictive. Infection with GNB
      was independently associated with death (relative risk, 3.4; 95% CI, 1.6-7.4; P
      =.002). CONCLUSIONS: In our setting, in every tenth patient with CAP, an etiology
      due to GNB has to be considered. Patients with probable aspiration, previous
      hospitalization or antimicrobial treatment, and pulmonary comorbidity are
      especially prone to GNB. These pathogens are also an independent risk factor for
      death in patients with CAP.

PMID- 12196084
TI  - Depression-related costs in heart failure care.
AB  - BACKGROUND: Behavioral factors may play a role in heart failure (HF) care costs
      by increasing hospital readmission rates. This study sought to estimate the
      effect of depression on health care costs for patients hospitalized for HF.
      METHODS: A 3-year retrospective cohort study of a staff-model health maintenance
      organization. Following a first hospitalization with a primary diagnosis of HF,
      1098 health maintenance organization patients were evaluated. Median annualized
      health care costs for 3 depression groups were identified: (1) no depression (n =
      672; cost, $7474), (2) antidepressant prescription only (n = 312; cost, $11 012),
      and (3) antidepressant prescription and depression diagnosis recorded (n = 114;
      cost, $9550). Depression and HF status were determined through diagnostic,
      laboratory, and pharmacy records. Actual utilization and cost values were derived
      from administrative data. RESULTS: After adjusting for age, sex, medical
      comorbidity, and length of stay at index hospitalization (as proxy for HF
      severity), costs were 26% higher in the antidepressant prescription only group
      and 29% higher in the antidepressant prescription and depression diagnosis
      recorded group when compared with the no depression group (both P<.001).
      Increased inpatient and outpatient utilization contributed to the increased
      costs. CONCLUSION: Costs of care for patients hospitalized for HF are
      significantly higher for patients with evidence of depression.

PMID- 12196085
TI  - Overweight and obesity as determinants of cardiovascular risk: the Framingham
      experience.
AB  - BACKGROUND: To our knowledge, no single investigation concerning the long-term
      effects of overweight status on the risk for hypertension, hypercholesterolemia,
      diabetes mellitus, and cardiovascular sequelae has been reported. METHODS:
      Relations between categories of body mass index (BMI), cardiovascular disease
      risk factors, and vascular disease end points were examined prospectively in
      Framingham Heart Study participants aged 35 to 75 years, who were followed up to
      44 years. The primary outcome was new cardiovascular disease, which included
      angina pectoris, myocardial infarction, coronary heart disease, or stroke.
      Analyses compared overweight (BMI [calculated as weight in kilograms divided by
      the square of height in meters], 25.0-29.9) and obese persons (BMI > or =30) to a
      referent group of normal-weight persons (BMI, 18.5-24.9). RESULTS: The age
      adjusted relative risk (RR) for new hypertension was highly associated with
      overweight status (men: RR, 1.46; women: RR, 1.75). New hypercholesterolemia and
      diabetes mellitus were less highly associated with excess adiposity. The age
      adjusted RR (confidence interval [CI]) for cardiovascular disease was increased
      among those who were overweight (men: 1.21 [1.05-1.40]; women: 1.20 [1.03-1.41])
      and the obese (men: 1.46 [1.20-1.77]; women: 1.64 [1.37-1.98]). High population
      attributable risks were related to excess weight (BMI > or =25) for the outcomes
      hypertension (26% men; 28% women), angina pectoris (26% men; 22% women), and
      coronary heart disease (23% men; 15% women). CONCLUSIONS: The overweight category
      is associated with increased relative and population attributable risk for
      hypertension and cardiovascular sequelae. Interventions to reduce adiposity and
      avoid excess weight may have large effects on the development of risk factors and
      cardiovascular disease at an individual and population level.

PMID- 12196086
TI  - Tuberculosis recurrences: reinfection plays a role in a population whose
      clinical/epidemiological characteristics do not favor reinfection.
AB  - BACKGROUND: Tuberculosis (TB) recurrences can be due to either reactivation by
      the same strain (standard assumption) or reinfection by a new strain. Reinfection
      has mainly been studied in selected populations with a high risk of reexposure to
      TB. Our aim was to analyze the role of reinfection in TB recurrences in
      unselected populations, without the clinical/epidemiological circumstances that
      favor the involvement of a new different strain of Mycobacterium tuberculosis in
      the recurrence. METHODS: A molecular typing analysis was performed with 92
      sequential isolates of M tuberculosis from 43 patients with recurrent TB, during
      a 12-year period. The subjects were both positive and negative for the human
      immunodeficiency virus, most did not adhere to anti-TB therapy, and they lived in
      an area with a moderate incidence of TB. Recurrence was considered as being
      caused by reinfection when the molecular fingerprints for the strains involved in
      the sequential episodes of TB were different. RESULTS: In 14 (33%) of the 43
      patients, different M tuberculosis strains were involved in the first and in
      subsequent episodes of TB. Reinfection was found for patients who were both
      positive and negative for the human immunodeficiency virus, and most patients did
      not adhere to anti-TB therapy. Differences between the reinfection and
      reactivation groups were not significant (P =.77) according to the time interval
      between episodes. CONCLUSIONS: Reinfection plays an important role in recurrent
      TB in a population without the clinical/epidemiological circumstances that are
      usually assumed to favor it. Reinfection should, thus, be considered as a cause
      of TB recurrences in a wider context than before.

PMID- 12196087
TI  - The clinical usefulness of D-dimer testing in cancer patients with suspected deep
      venous thrombosis.
AB  - BACKGROUND: Little is known about the diagnostic value of a D-dimer test in
      cancer patients with clinically suspected deep venous thrombosis (DVT).
      OBJECTIVE: To evaluate the clinical utility of a whole blood rapid D-dimer test
      (SimpliRED) in cancer patients compared with noncancer patients. METHODS: In
      consecutive patients with suspected lower limb DVT, a D-dimer test and
      ultrasonogram were performed. Cancer status was recorded at presentation. If the
      D-dimer test and ultrasonogram results were normal, DVT was considered absent. If
      the D-dimer result was abnormal, ultrasonography was performed again 1 week
      later. Anticoagulant therapy was only instituted in those patients with an
      abnormal ultrasonography result. All patients were followed up for 3 months to
      record subsequent thromboembolic events. The accuracy of the D-dimer test was
      assessed, and the efficiency and safety of withholding additional ultrasonography
      in cancer patients with normal results on both D-dimer and ultrasonography was
      compared with noncancer patients. RESULTS: A total of 1739 consecutive patients
      were studied, 217 (12%) of whom had cancer. The negative predictive value of the
      D-dimer test was 97% in both cancer and noncancer patients. In 63 (29%) of all
      217 cancer patients, the D-dimer and ultrasonography results were normal at
      referral; therefore, the diagnosis of DVT was refuted and anticoagulant treatment
      was withheld. In these 63 patients, one thromboembolic event occurred during
      follow-up (1.6%; 95% confidence interval, 0.04%-8.53%). CONCLUSIONS: The negative
      predictive value of a whole blood D-dimer test in cancer patients seems as high
      as in noncancer patients. In a substantial proportion of cancer patients, the
      diagnosis can likely be refuted at referral, based on normal D-dimer test and
      ultrasonogram results. Furthermore, it seems safe to withhold anticoagulant
      therapy in these patients.

PMID- 12196088
TI  - A utilization management intervention to reduce unnecessary testing in the
      coronary care unit.
AB  - BACKGROUND: There have been no studies of interventions to reduce test
      utilization in the coronary care unit. OBJECTIVE: To determine whether a 3-part
      intervention in a coronary care unit could decrease utilization without affecting
      clinical outcomes. METHODS: Practice guidelines for routine laboratory and chest
      radiographic testing were developed by a multidisciplinary team, using evidence
      based recommendations when possible and expert opinion otherwise. These
      guidelines were incorporated into the computer admission orders for the coronary
      care unit at a large teaching hospital, and educational efforts were targeted at
      the house staff and nurses. Utilization during the 3-month intervention period
      was compared with utilization during the same 3 months in the prior year. The
      hospital's medical intensive care unit, which did not receive the specific
      intervention, provided control data. RESULTS: During the intervention period,
      there were significant reductions in utilization of all chemistry tests (from 7%
      to 40%). Reductions in ordering of complete blood counts, arterial blood gas
      tests, and chest radiographs were not statistically significant. After
      controlling for trends in the control intensive care unit, however, the
      reductions in arterial blood gas tests (P =.04) and chest radiographs (P<.001)
      became significant. The reductions in potassium, glucose, calcium, magnesium, and
      phosphorus testing, but not other chemistries, remained significant. The
      estimated reduction in expenditures for "routine" blood tests and chest
      radiographs was 17% (P<.001). There were no significant changes in length of
      stay, readmission to intensive care, hospital mortality, or ventilator days.
      CONCLUSION: The utilization management intervention was associated with
      significant reductions in test ordering without a measurable change in clinical
      outcomes.

PMID- 12196089
TI  - A survey of oral vitamin K use by anticoagulation clinics.
AB  - BACKGROUND: Despite published reports of its safety and efficacy, oral vitamin K
      (phytonadione) may not be widely used for patients with warfarin-associated
      coagulopathy. We tested the hypothesis that recommendations for phytonadione use
      from the American College of Chest Physicians (ACCP) Fifth Consensus Conference
      on Antithrombotic Therapy are not routinely incorporated into the clinical
      practice of many anticoagulation clinics. METHODS: Surveys were mailed to 100
      separate clinics in the southwestern region of the United States that are members
      of the Anticoagulation Forum, an association of anticoagulation clinic personnel
      and medical directors in the United States and Canada. Respondents were presented
      with 4 scenarios involving asymptomatic patients taking warfarin whose
      international normalized ratio is supratherapeutic. In each scenario, the
      respondents were told the patient's international normalized ratio and whether
      the patient was at "high" risk for bleeding. RESULTS: Of 53 respondents, 13 (25%)
      indicated that their clinics never use oral phytonadione. Eighteen (34%)
      indicated that their clinics use subcutaneous phytonadione, despite the absence
      of a recommendation for this in the ACCP guidelines published in 1998. For each
      scenario, we made a judgment as to whether the respondent's management was
      consistent with guidelines found in the ACCP Fifth Consensus Conference on
      Antithrombotic Therapy. Overall, only 17 respondents (32%) provided all 4 answers
      consistent with the ACCP recommendations. CONCLUSION: For patients with
      supratherapeutic international normalized ratio values, our survey suggests that
      a substantial number of anticoagulation clinics underutilize oral phytonadione.

PMID- 12196090
TI  - Medication errors observed in 36 health care facilities.
AB  - BACKGROUND: Medication errors are a national concern. OBJECTIVE: To identify the
      prevalence of medication errors (doses administered differently than ordered).
      DESIGN: A prospective cohort study. SETTING: Hospitals accredited by the Joint
      Commission on Accreditation of Healthcare Organizations, nonaccredited hospitals,
      and skilled nursing facilities in Georgia and Colorado. PARTICIPANTS: A
      stratified random sample of 36 institutions. Twenty-six declined, with random
      replacement. Medication doses given (or omitted) during at least 1 medication
      pass during a 1- to 4-day period by nurses on high medication-volume nursing
      units. The target sample was 50 day-shift doses per nursing unit or until all
      doses for that medication pass were administered. METHODS: Medication errors were
      witnessed by observation, and verified by a research pharmacist (E.A.F.).
      Clinical significance was judged by an expert panel of physicians. MAIN OUTCOME
      MEASURE: Medication errors reaching patients. RESULTS: In the 36 institutions,
      19% of the doses (605/3216) were in error. The most frequent errors by category
      were wrong time (43%), omission (30%), wrong dose (17%), and unauthorized drug
      (4%). Seven percent of the errors were judged potential adverse drug events.
      There was no significant difference between error rates in the 3 settings (P
      =.82) or by size (P =.39). Error rates were higher in Colorado than in Georgia (P
      =.04) CONCLUSIONS: Medication errors were common (nearly 1 of every 5 doses in
      the typical hospital and skilled nursing facility). The percentage of errors
      rated potentially harmful was 7%, or more than 40 per day in a typical 300
      patient facility. The problem of defective medication administration systems,
      although varied, is widespread.

PMID- 12196091
TI  - Subdural hematoma following lumbar puncture.
AB  - A post-dural puncture headache is a potential complication of a lumbar puncture.
      Physicians should be able to readily diagnose and treat this potential
      complication. Described here is a patient who developed an unresolving post-dural
      puncture headache that then developed into a subdural hematoma. A subdural
      hematoma is a rare complication following lumbar punctures. Unresolving headaches
      following a lumbar puncture should prompt aggressive investigation.

PMID- 12196092
TI  - Comments, opinions, and brief case reports: biosurgical debridement facilitates
      healing of chronic skin ulcers.

PMID- 12196093
TI  - Novartis Medal Lecture. Antibodies: a paradigm for the evolution of molecular
      recognition.
AB  - Novel proteins have been elaborated over evolutionary time by an iterative
      alternation of mutation and selection. In a similar way, the humoral immune
      system also uses an iterative alternation of mutation and selection to generate
      novel antibodies that display a high affinity for their cognate antigen -- but
      this is achieved in a matter of a days. Gene rearrangement is used to produce a
      primary repertoire of antibodies and, on entering the body, antigen triggers the
      clonal expansion of those B lymphocytes that express a cognate antibody, albeit
      one of low affinity. Rapid and specific affinity maturation is then achieved by
      subjecting the immunoglobulin genes in the rapidly expanding B cells to a period
      of intense mutation. The intensity of this mutational assault is tolerated
      because it is targeted specifically to the immunoglobulin genes, causing
      relatively little damage to other loci. Antigen-mediated selection then allows
      the preferential expansion of those mutants expressing antibodies displaying
      improved binding characteristics. Here, studies are described that have been
      performed to glean insight into the mechanisms of the hypermutation and selection
      processes. Experiments are also described in which an attempt has been made to
      recapitulate aspects of physiological antibody generation in vitro, allowing the
      development of novel approaches to the generation of proteins with high-affinity
      binding sites.

PMID- 12196094
TI  - Specificity of 14-3-3 isoform dimer interactions and phosphorylation.
AB  - Proteins that interact with 14-3-3 isoforms are involved in regulation of the
      cell cycle, intracellular trafficking/targeting, signal transduction,
      cytoskeletal structure and transcription. Recent novel roles for 14-3-3 isoforms
      include nuclear trafficking the direct interaction with cruciform DNA and with a
      number of receptors, small G-proteins and their regulators. Recent findings also
      show that the mechanism of interaction is also more complex than the initial
      finding of the novel phosphoserine/threonine motif. Non-phosphorylated binding
      motifs that can also be of high affinity may show a more isoform-dependent
      interaction and binding of a protein through two distinct binding motifs to a
      dimeric 14-3-3 may also be essential for full interaction. Phosphorylation of
      specific 14-3-3 isoforms can also regulate interactions. In many cases, they show
      a distinct preference for a particular isoform(s) of 14-3-3. A specific
      repertoire of dimer formation may influence which of the 14-3-3-interacting
      proteins could be brought together. Mammalian and yeast 14-3-3 isoforms show a
      preference for dimerization with specific partners in vivo.

PMID- 12196095
TI  - Survival-promoting functions of 14-3-3 proteins.
AB  - The 14-3-3 proteins are a family of phosphoserine/phosphothreonine-binding
      molecules that control the function of a wide array of cellular proteins. We
      suggest that one function of 14-3-3 is to support cell survival. 14-3-3 proteins
      promote survival in part by antagonizing the activity of associated proapoptotic
      proteins, including Bad and apoptosis signal-regulating kinase 1 (ASK1). Indeed,
      expression of 14-3-3 inhibitor peptides in cells is sufficient to induce
      apoptosis. Interestingly, these 14-3-3 antagonist peptides can sensitize cells
      for effective killing by anticancer agents such as cisplatin. Thus, 14-3-3 may be
      part of the cellular machinery that maintains cell survival, and targeting 14-3-3
      ligand interactions may be a useful strategy to enhance the efficacy of
      conventional anticancer agents.

PMID- 12196096
TI  - 14-3-3 Proteins and photoneuroendocrine transduction: role in controlling the
      daily rhythm in melatonin.
AB  - This paper describes the role 14-3-3 proteins play in vertebrate
      photoneuroendocrine transduction. 14-3-3 proteins form a complex with
      arylalkylamine N-acetyltransferase (AANAT), the enzyme which turns melatonin
      production on during the day and off at night. Complex formation is triggered at
      night by cAMP-dependent phosphorylation of the enzyme, and results in activation
      and protection against proteolysis. This enhances melatonin production >10-fold.
      Light exposure results in dephosphorylation of the enzyme and disassociation from
      14-3-3, leading to destruction and a rapid drop in melatonin production and
      release and circulating levels.

PMID- 12196097
TI  - Plant 14-3-3 protein families: evidence for isoform-specific functions?
AB  - 14-3-3 proteins regulate a wide range of target proteins via direct protein
      protein interactions. The target-binding domain in 14-3-3 proteins is highly
      conserved, suggesting similar biochemical properties for all 14-3-3s. However,
      higher eukaryotes possess multiple 14-3-3 genes, and these genes exhibit diverse
      patterns of gene expression within any one organism. This tends to suggest
      specific functions for particular genes. Some biochemical data suggest 14-3-3
      isoform-specific protein-protein interactions, whereas other studies conclude
      that apparent isoform-specificity is the result of differences in expression
      patterns rather than in the biochemical properties of 14-3-3 isoforms. Here we
      discuss evidence that demonstrates that the expression levels of 14-3-3 proteins
      in cells are important for regulating the activity of their target proteins, and
      further that the elimination of individual 14-3-3 isoforms can result in
      detectable phenotypes. We also examine evidence that 14-3-3 isoform specificity
      can in some cases reflect differing biochemical properties as well as
      differential transcriptional regulation.

PMID- 12196098
TI  - Affinity purification of diverse plant and human 14-3-3-binding partners.
AB  - Many proteins that bind to a 14-3-3 column in competition with a 14-3-3-binding
      phosphopeptide have been purified from plant and mammalian cells and tissues. New
      14-3-3 targets include enzymes of biosynthetic metabolism, vesicle trafficking,
      cell signalling and chromatin function. These findings indicate central
      regulatory roles for 14-3-3s in partitioning carbon among the pathways of sugar,
      amino acid, nucleotide and protein biosynthesis in plants. Our results also
      suggest that the current perception that 14-3-3s bind predominantly to signalling
      proteins in mammalian cells is incorrect, and has probably arisen because of the
      intensity of research on mammalian signalling and for technical reasons.

PMID- 12196099
TI  - Use of 14-3-3 in the diagnosis of Creutzfeldt-Jakob disease.
AB  - The transmissible spongiform encephalopathies include human diseases such as
      Creutzfeldt-Jakob disease (CJD) and kuru as well as animal diseases such as
      scrapie and bovine spongiform encephalopathy (BSE). The emergence of variant CJD,
      which is causally related to BSE, has generated much interest in the development
      of rapid and sensitive diagnostic tests for the pre-mortem diagnosis of CJD. In
      1986 two proteins were detected in the cerebrospinal fluid (CSF) of patients with
      sporadic CJD. These proteins were later demonstrated to be members of the 14-3-3
      family, and tests for the detection of CSF 14-3-3 were developed. A number of
      studies have shown that the detection of CSF 14-3-3 is an accurate test for
      sporadic CJD, although the results with variant CJD are less promising.

PMID- 12196100
TI  - Specific 14-3-3 isoform detection and immunolocalization in prion diseases.
AB  - 14-3-3 proteins are involved in signalling processes in neuronal cells. Using
      isoform-specific antibodies we have examined the variation in 14-3-3 isoform
      neurolocation in normal and scrapie-infected murine brain and show that in
      defined areas of the brain there are significant changes associated with the
      pathology of the disease process. The appearance of 14-3-3 proteins in the
      cerebrospinal fluid (CSF) is a consequence of neuronal disease and the detection
      of specific isoforms of the 14-3-3 proteins in the CSF is characteristic of some
      neurodegenerative diseases. In this study, monitoring specifically for the gamma
      14-3-3 isoform in the CSF by both Western-blot analysis and ELISA we can show a
      level of correlation between the assays.

PMID- 12196101
TI  - Effect of multiple phosphorylation events on the transcription factors FKHR,
      FKHRL1 and AFX.
AB  - The insulin-stimulated phosphoinositide 3-kinase (PI 3-kinase)/3-phosphoinositide
      dependent kinase-1 (PDK1)/protein kinase B (PKB) kinase cascade is believed to
      play a critical role in metabolic control and cell survival, largely mediated
      through PKB phosphorylation of many proteins. Recent findings demonstrate that
      the transcription factors FKHR (forkhead in rhabdomyosarcoma), AFX (ALL1 fused
      gene from chromosome X) and FKHRL1 (FKHR-like 1; termed FKHR isoforms) are
      phosphorylated by PKB in cells, leading to their exit from the nucleus. These
      exciting results suggest that FKHR isoforms may be critical effectors of PI 3
      kinase/PDK1/PKB signalling in vivo.

PMID- 12196102
TI  - 14-3-3s are DNA-replication proteins.
AB  - 14-3-3 proteins are conserved multifunctional molecules, involved in many
      biological processes. Several 14-3-3 isoforms were recently shown to be cruciform
      DNA-binding proteins, which is a new activity ascribed to the 14-3-3 family. As
      cruciform-binding proteins, 14-3-3 proteins are putatively involved in the
      regulation of DNA replication. Inverted repeat sequences that are able to extrude
      into cruciform structures are a common feature of replication origins in both
      prokaryotes and eukaryotes. The involvement of cruciform structures in the
      initiation of DNA replication has been demonstrated. A leading model of 14-3-3
      function proposes that they facilitate critical protein-protein interactions,
      thus serving as a central component of a wide variety of cellular processes.

PMID- 12196103
TI  - Exoenzyme S binds its cofactor 14-3-3 through a non-phosphorylated motif.
AB  - 14-3-3 proteins belong to a family of conserved molecules, which play a
      regulatory role and participate in signal transduction and checkpoint control
      pathways. 14-3-3 proteins bind phosphoserine-phosphorylated ligands, such as the
      Raf-1 kinase and Bad, through recognition of the phosphorylated consensus motif,
      RSXpSXP (where pS is phosphoserine). Recently, a phosphorylation-independent
      interaction has been reported to occur between 14-3-3 and a small number of
      proteins, for example the 43 kDa inositol polyphosphate 5-phosphatase,
      glycoprotein Ib, p75NTR-associated cell-death executor (NADE) and the bacterial
      ADP-ribosyltransferase toxin exoenzyme S (ExoS). It has been suggested that
      specific residues of 14-3-3 proteins are required for activation of the bacterial
      toxin ExoS. An unphosphorylated peptide derived from a phage display library,
      known as the R18 peptide, and a synthetic peptide derived from ExoS inhibit the
      interaction between ExoS and 14-3-3. In this report we identify the amino acid
      sequence on ExoS which is responsible for its specific interaction with 14-3-3,
      both in vitro and in vivo. In addition, we believe that this interaction is
      critical for the ADP-ribosylation of an endogenous target, Ras, by ExoS both in
      vitro and in vivo. Loss of the 14-3-3-binding site on ExoS results in an ExoS
      molecule that is unable to efficiently inactivate Ras and shows a reduced
      capacity to change the morphology of infected cells, together with reduced
      killing activity.

PMID- 12196104
TI  - Transgenic 14-3-3 isoforms in plants: the metabolite profiling of repressed 14-3
      3 protein synthesis in transgenic potato plants.
AB  - 14-3-3 proteins are abundant eukaryotic proteins that interact with many other
      proteins, thereby modulating their function and thus cell metabolism. The data
      from mRNA analysis confirm the developmental regulation of 14-3-3 isoform
      expression in potato plants. In order to test whether or not 14-3-3 protein
      expression affects plant phenotype and metabolism, transgenic potato plants
      either overexpressing Cucurbita pepo 14-3-3 or underexpressing endogenous 14-3-3
      isoforms were analysed. An increase in tuber number and a decrease in tuber size
      in the overexpressed transformant was observed; the transgenic plants contain
      more chlorophyll than the control and they lose it more slowly than the control
      when transferred to the dark. The 14-3-3-repressed transgenic plants showed a
      decrease in tuber number and an increase in tuber size; an increase in the fresh
      weight of the transgenic tubers was also detected. The increased catecholamine
      level was accompanied by an increased ratio of soluble sugars to starch in
      overexpressed transformant. The opposite effect was detected in 14-3-3-repressed
      transgenic plants. All the repressed plants showed significant increases in
      nitrate reductase (NR) activity, suggesting that the regulation of NR occurs in
      vivo, and is not isoform-dependent. The increase in NR activity resulted in a
      significant decrease in nitrate level. The level of sucrose phosphate synthase
      activity was also significantly increased in all 14-3-3-underexpressed
      transgenes, and remarkably the increase in enzyme activity was accompanied by
      respective changes in sucrose levels in the tubers. The most intriguing finding
      was the significant (2-3-fold) increase in ethylene content in all the 14-3-3
      repressed transgenic lines, which probably resulted from a methionine level
      increase. The substantial increase of ethylene level in the repressed forms might
      explain the significant shortening of the vegetation period of the analysed
      transgenic plants.

PMID- 12196106
TI  - Plant 14-3-3 proteins assist ion channels and pumps.
AB  - Turgor pressure is a cellular parameter, important for a range of physiological
      processes in plants, like cell elongation, gas exchange and
      gravitropic/phototropic bending. Regulation of turgor pressure involves ion and
      water transport at the expense of metabolic energy (ATP). The primary pump in the
      plasma membrane (the H(+)-ATPase) is a key player in turgor regulation since it
      provides the driving force for ion uptake, followed by water influx through
      osmosis. Using the phytotoxin fusicoccin (a well-known activator of the ATPase)
      as a tool, 14-3-3 proteins were identified as regulators of the H(+)-ATPase.
      Since fusicoccin has a dramatic effect on K(+) accumulation and cellular
      respiration as well, we studied whether 14-3-3 proteins play a role in the
      regulation of the mitochondrial F(0)F(1)-ATP synthase and ion channels in the
      vacuolar and plasma membranes. Besides the plasma membrane H(+)-ATPase, we have
      identified thus far at least four other transport proteins that are regulated by
      14-3-3 proteins. The mechanism of regulation will be described and the
      possibility that 14-3-3 proteins act as coordinators of ion transporters with
      varied but interdependent functions will be discussed.

PMID- 12196105
TI  - Phosphorylation-independent interaction between 14-3-3 protein and the plant
      plasma membrane H+-ATPase.
AB  - 14-3-3 proteins interact with a novel phosphothreonine motif (Y(946)pTV) at the
      extreme C-terminal end of the plant plasma membrane H(+)-ATPase molecule.
      Phosphorylation-independent binding of 14-3-3 protein to the YTV motif can be
      induced by the fungal phytotoxin fusicoccin. The molecular basis for the
      phosphorylation-independent interaction between 14-3-3 and H(+)-ATPase in the
      presence of fusicoccin has been investigated in more detail. Fusicoccin binds to
      a heteromeric receptor that involves both 14-3-3 protein and H(+)-ATPase. Binding
      of fusicoccin is dependent upon the YTV motif in the H(+)-ATPase and, in
      addition, requires residues further upstream of this motif. Apparently, 14-3-3
      proteins interact with the unusual epitope in H(+)-ATPase via its conserved
      amphipathic groove. This implies that very diverse epitopes bind to a common
      structure in the 14-3-3 protein.

PMID- 12196107
TI  - Transcriptional regulation of the calcitonin receptor gene.
AB  - Calcitonin is a 32-amino-acid peptide hormone that is produced by parafollicular
      cells of the thyroid gland in response to increased levels of extracellular
      calcium. In this article we review our previous and current research on the
      transcriptional regulation of the pig and human calcitonin receptor (CTR) gene.
      Initially, our experiments on the transcriptional analysis of the pig CTR gene in
      transgenic mice are examined, followed by our studies on the cloning of the human
      CTR (hCTR) gene promoter and its transcriptional activity in hCTR-positive cell
      lines. We further describe the activity of the hCTR promoter in transgenic mice
      and review current experiments to identify transcriptional regulatory elements
      and the transcription factors they interact with, which direct the tissue
      specific expression pattern of hCTR promoter activity.

PMID- 12196108
TI  - Corticotropin-releasing hormone receptors.
AB  - Corticotropin-releasing hormone (CRH) and related peptides (urocortins,
      sauvagine, urotensin) play a central role in the co-ordination of autonomic,
      behavioural, cardiovascular, immune and endocrine responses to stressful stimuli.
      Their actions are mediated through activation of two types of G-protein-coupled
      receptors encoded by separate genes. In this review we focus on the diverse
      structural and functional characteristics of the family of CRH-like peptides and
      their receptors.

PMID- 12196109
TI  - Adrenomedullin: receptor and signal transduction.
AB  - Adrenomedullin is a vascular tissue peptide and a member of the calcitonin family
      of peptides, which includes calcitonin, calcitonin-gene-related peptide (CGRP)
      and amylin. Its many biological actions are mediated via CGRP type 1 (CGRP(1))
      receptors and by specific adrenomedullin receptors. Although the pharmacology of
      these receptors is distinct, they are both represented in molecular terms by the
      type II family G-protein-coupled receptor, calcitonin-receptor-like receptor
      (CRLR). The specificity here is defined by co-expression of receptor-activity
      modifying proteins (RAMPs). CGRP(1) receptors are represented by CRLR and RAMP1,
      and specific adrenomedullin receptors by CRLR and RAMP2 or 3. Here we discuss how
      CRLR/RAMP2 relates to adrenomedullin binding, pharmacology and pathophysiology,
      and how chemical cross-linking of receptor-ligand complexes in tissue relates to
      that in CRLR/RAMP2-expressing cells. CRLR, like other type II family G-protein
      coupled receptors, signals via G(s) and adenylate cyclase activation. We
      demonstrated that adrenomedullin signalling in cell lines expressing specific
      adrenomedullin receptors followed this expected pattern.

PMID- 12196111
TI  - Additional signals from VPAC/PAC family receptors.
AB  - The receptors for the neuropeptides vasoactive intestinal polypeptide and
      pituitary adenylate cyclase-activating polypeptide are strong activators of
      adenylate cyclase, but recent evidence suggests that they can elicit a number of
      additional intracellular signals. Some of these are likely to be downstream of
      the conventional adenylate cyclase pathway, but it is now clear that others
      reflect novel primary coupling events of the receptors.

PMID- 12196110
TI  - Identification of secretin, vasoactive intestinal peptide and glucagon binding
      sites: from chimaeric receptors to point mutations.
AB  - We have identified two basic residues that are important for the recognition of
      secretin and vasoactive intestinal peptide (VIP) by their respective receptors.
      These two peptides containing an Asp residue at position 3 interacted with an
      arginine residue in transmembrane helix 2 (TM2) of the receptor, and the lysine
      residue in extracellular loop 1 (ECL1) stabilized the active receptor
      conformation induced by the ligand. The glucagon receptor possesses a Lys instead
      of an Arg in TM2, and an Ile instead of Lys in ECL1; it markedly prefers a Gln
      side chain in position 3 of the ligand. Our results suggested that, in the wild
      type receptor, the Ile side chain prevented access to the TM2 Lys side chain, but
      oriented the glucagon Gln(3) side chain to its proper binding site. In the double
      mutant, the ECL1 Lys allowed an interaction between negatively charged residues
      in position 3 of glucagon and the TM2 Arg, resulting in efficient receptor
      activation by [Asp(3)]glucagon as well as by glucagon.

PMID- 12196112
TI  - A small sequence in the third intracellular loop of the VPAC(1) receptor is
      responsible for its efficient coupling to the calcium effector.
AB  - The stimulatory effect of vasoactive intestinal peptide (VIP) on the
      intracellular calcium concentration ([Ca(2+)](i)) has been investigated in
      Chinese hamster ovary cells stably transfected with the reporter gene aequorin,
      and expressing human VPAC(1), VPAC(2), chimaeric VPAC(1)/VPAC(2) or mutated
      receptors. The VIP-induced increase in [Ca(2+)](i) was linearly correlated with
      receptor density, and was higher in cells expressing VPAC(1) receptors than in
      cells expressing a similar density of VPAC(2) receptors. The study was performed
      to establish the receptor sequence responsible for this difference.
      VPAC(1)/VPAC(2) chimaeric receptors were first used for broad positioning: those
      receptors having the third intracellular loop (IC3) of the VPAC(1) or the VPAC(2)
      receptor behaved, in this respect, phenotypically like VPAC(1) and VPAC(2)
      receptors respectively. Replacement in the VPAC(2) receptor of the sequence
      comprising residues 315-318 (VGGN) within IC3 by its VPAC(1) receptor counterpart
      (residues 328-331; IRKS) and the introduction of VGGN instead of IRKS into
      VPAC(1) was sufficient to mimic VPAC(1) and VPAC(2) receptor characteristics
      respectively. Thus a small sequence in the IC3 domain of the VPAC(1) receptor is
      responsible for the efficient agonist-stimulated increase in [Ca(2+)](i).

PMID- 12196113
TI  - Interaction of calcitonin-gene-related peptide with its receptors.
AB  - The receptor for calcitonin-gene-related peptide (CGRP) is a heterodimer formed
      by calcitonin-receptor-like receptor (CRLR), a type II (family B) G-protein
      coupled receptor, and receptor-activity-modifying protein 1 (RAMP1), a single
      membrane-pass protein. It is likely that the first seven or so amino acids of
      CGRP (which form a disulphide-bonded loop) interact with the transmembrane domain
      of CRLR to cause receptor activation. The rest of the CGRP molecule falls into
      three domains. Residues 28-37 and 8-18 are normally required for high-affinity
      binding, while residues 19-27 form a hinge region. The 28-37 region is almost
      certainly in direct contact with the receptor; 8-18 may make additional receptor
      contacts or may stabilize an appropriate conformation of 28-37. It is likely that
      these regions of CGRP interact both with CRLR and with the extracellular domain
      of RAMP1.

PMID- 12196114
TI  - Functional relevance of G-protein-coupled-receptor-associated proteins,
      exemplified by receptor-activity-modifying proteins (RAMPs).
AB  - The calcitonin (CT) receptor (CTR) and the CTR-like receptor (CRLR) are close
      relatives within the type II family of G-protein-coupled receptors, demonstrating
      sequence identity of 50%. Unlike the interaction between CT and CTR, receptors
      for the related hormones and neuropeptides amylin, CT-gene-related peptide (CGRP)
      and adrenomedullin (AM) require one of three accessory receptor-activity
      modifying proteins (RAMPs) for ligand recognition. An amylin/CGRP receptor is
      revealed when CTR is co-expressed with RAMP1. When complexed with RAMP3, CTR
      interacts with amylin alone. CRLR, initially classed as an orphan receptor, is a
      CGRP receptor when co-expressed with RAMP1. The same receptor is specific for AM
      in the presence of RAMP2. Together with human RAMP3, CRLR defines an AM receptor,
      and with mouse RAMP3 it is a low-affinity CGRP/AM receptor. CTR-RAMP1,
      antagonized preferentially by salmon CT-(8-32) and not by CGRP-(8-37), and CRLR
      RAMP1, antagonized by CGRP-(8-37), are two CGRP receptor isotypes. Thus amylin
      and CGRP interact specifically with heterodimeric complexes between CTR and RAMP1
      or RAMP3, and CGRP and AM interact with complexes between CRLR and RAMP1, RAMP2
      or RAMP3.

PMID- 12196115
TI  - Receptor component protein (RCP): a member of a multi-protein complex required
      for G-protein-coupled signal transduction.
AB  - The calcitonin-gene-related peptide (CGRP) receptor component protein (RCP) is a
      148-amino-acid intracellular protein that is required for G-protein-coupled
      signal transduction at receptors for the neuropeptide CGRP. RCP works in
      conjunction with two other proteins to constitute a functional CGRP receptor:
      calcitonin-receptor-like receptor (CRLR) and receptor-activity-modifying protein
      1 (RAMP1). CRLR has the stereotypical seven-transmembrane topology of a G-protein
      coupled receptor; it requires RAMP1 for trafficking to the cell surface and for
      ligand specificity, and requires RCP for coupling to the cellular signal
      transduction pathway. We have made cell lines that expressed an antisense
      construct of RCP and determined that CGRP-mediated signal transduction was
      reduced, while CGRP binding was unaffected. Furthermore, signalling at two other
      endogenous G-protein-coupled receptors was unaffected, suggesting that RCP was
      specific for a limited subset of receptors.

PMID- 12196116
TI  - Interaction of G-protein-coupled receptors with synaptic scaffolding proteins.
AB  - The calcium-independent receptors for latrotoxin (CIRL1-CIRL3) constitute a
      family of seven-transmembrane receptors with an unsually large N-terminal
      extracellular domain which comprises several motifs usually found in cell
      adhesion molecules. By yeast two-hybrid screening, we have identified the
      intracellular C-termini of CIRL1 and CIRL2 as interaction partners of the PDZ
      domain of the proline-rich synapse-associated protein (ProSAP)/somatostatin
      receptor-interacting protein (SSTRIP) family of postsynaptic proteins (SSTRIP,
      ProSAP1 and ProSAP2, also known as shank1-shank3 respectively). Overlay assays
      indicate that the ProSAP1/shank2 PDZ domain in particular interacts strongly with
      the C-terminus of CIRL1 and CIRL2. Co-immunoprecipitation of ProSAP1 and CIRL1
      (but not CIRL2) from rat brain extracts indicates that this interaction also
      occurs in vivo in rat brain. The known postsynaptic localization of ProSAP1, as
      well as our observation that CIRL1 (but not CIRL2) is enriched in postsynaptic
      density preparations from the rat brain, suggests that CIRL1 is localized pre- as
      well as post-synaptically in the central nervous system.

PMID- 12196118
TI  - Bioinformatics and type II G-protein-coupled receptors.
AB  - The best known family B, or Type II, G-protein-coupled receptors (GPCRs)
      recognize peptides as ligands. The receptors for corticotrophin-releasing factor,
      parathyroid hormone and secretin typify this group. However, there are only 15
      such GPCRs. Many other receptors share sequence homology and have been assigned
      to this family. The ten 'Frizzled' and one 'Smoothened' receptors show the lowest
      sequence homology and are not necessarily G-protein coupled. Drosophila genetics
      have enabled our understanding of their biology. In contrast, relatively little
      is known about the largest group with family B, the 33 'large amino termini' or
      large N-terminal family B seven-transmembrane (LNB 7TM) receptors. This review
      highlights the similarities found between family B receptors and provides a
      classification of LNB 7TM receptors.

PMID- 12196117
TI  - Development and potential of non-peptide antagonists for calcitonin-gene-related
      peptide (CGRP) receptors: evidence for CGRP receptor heterogeneity.
AB  - Calcitonin-gene-related peptide (CGRP) is a 37-amino-acid vasodilatory peptide,
      of which two isoforms, alpha CGRP and beta CGRP, have been described. The use of
      C-terminal fragments of CGRP peptide, such as human alpha CGRP-(8-37), has led to
      the pharmacological subdivision of CGRP receptors into CGRP-1 [high potency for
      binding of human alpha CGRP-(8-37)] and CGRP-2 (lower potency) receptors. We have
      recently developed BIBN4096BS, the first non-peptide CGRP antagonist, which has
      sub-nanomolar affinity for primate CGRP receptors. The use of BIBN4096BS has led
      to the discovery of further functional CGRP receptor heterogeneity in rat
      tissues. To further exploit BIBN4096BS as a pharmacological tool, we used
      BIBN4096BS in pig left anterior descending coronary vessels and cerebral basilar
      arteries, and compared functional with molecular data, characterizing CGRP
      receptor components. Our data show that, apart from a subdivision into CGRP-1 and
      -2 receptors, BIBN4096BS reveals additional functional differences between the
      actions of alpha CGRP and beta CGRP. However, evidence for CGRP receptor
      heterogeneity on a molecular level is scarce.

PMID- 12196119
TI  - X-ray crystallographic studies of IgG-Fc gamma receptor interactions.
AB  - Human Fc gamma receptors (Fc gamma Rs) for the Fc portion of IgG are major
      mediators of the adaptive immune response. Crystal structures of their
      extracellular domains were recently solved and shown to obey a common fold,
      resulting in a heart-shaped structure. Together with the multifunctional Fc
      fragment, whose structure was deciphered in the 1970s, the complex of an Fc gamma
      R with Fc was recently crystallized. Its crystal structure indicates that despite
      the dimeric character of the Fc fragment, only one Fc gamma R can bind to Fc, due
      to an introduced asymmetry within the homodimeric Fc, as well as by binding to
      symmetrically related residues of both Fc chains. Homology modelling suggested
      that the other Fc gamma Rs bind the Fc in a similar manner. The resolved complex
      structure can be regarded as a paradigm for Ig binding to Fc receptors and serves
      as a solid base for the design of compounds interfering with complex formation.
      Such molecules would be of invaluable benefit for the therapy of immunological
      disorders.

PMID- 12196120
TI  - Engineering therapeutic antibodies for improved function.
AB  - The binding sites on human IgG1 for human Fc gamma receptor (Fc gamma R) I, Fc
      gamma RIIa, Fc gamma RIIb, Fc gamma RIIIa and neonatal FcR have been mapped. A
      common set of IgG1 residues is involved in binding to all Fc gamma Rs, while Fc
      gamma RII and Fc gamma RIII utilize distinct sites outside this common set. In
      addition to residues which abrogated binding to the Fc gamma R, several positions
      were found which improved binding only to specific Fc gamma Rs or simultaneously
      improved binding to one type of Fc gamma R and reduced binding to another type.
      Selected IgG1 variants with improved binding to Fc gamma RIIIa were then tested
      in an in vitro antibody-dependent cellular cytotoxicity (ADCC) assay and showed
      an enhancement in ADCC when either peripheral blood mononuclear cells or natural
      killer cells were used.

PMID- 12196121
TI  - The human IgA-Fc alpha receptor interaction and its blockade by streptococcal IgA
      binding proteins.
AB  - IgA plays a key role in immune defence of the mucosal surfaces. IgA can trigger
      elimination mechanisms against pathogens through the interaction of its Fc region
      with Fc alpha Rs (receptors specific for the Fc region of IgA) present on
      neutrophils, macrophages, monocytes and eosinophils. The human Fc alpha R (CD89)
      shares homology with receptors specific for the Fc region of IgG (Fc gamma Rs)
      and IgE (Fc epsilon RIs), but is a more distantly related member of the receptor
      family. CD89 interacts with residues lying at the interface of the two domains of
      IgA Fc, a site quite distinct from the homologous regions at the top of IgG and
      IgE Fc recognized by Fc gamma R and Fc epsilon RI respectively. Certain
      pathogenic bacteria express surface proteins that bind to human IgA Fc.
      Experiments with domain-swap antibodies and mutant IgAs indicate that binding of
      three such proteins (Sir22 and Arp4 of Streptococcus pyogenes and beta protein of
      group B streptococci) depend on sites in the Fc interdomain region of IgA, the
      binding region also used by CD89. Further, we have found that the streptococcal
      proteins can inhibit interaction of IgA with CD89, and have thereby identified a
      mechanism by which a bacterial IgA-binding protein may modulate IgA effector
      function.

PMID- 12196122
TI  - The contrasting IgG-binding interactions of human and herpes simplex virus Fc
      receptors.
AB  - A virally encoded, high-affinity Fc receptor (FcR) is found on herpes simplex
      virus type 1 (HSV-1) particles and infected cells where its binding of non-immune
      IgG protects cells from host-mediated lysis. Whilst mutation or aglycosylation of
      the IgG CH2 domain reduced binding to human FcR, the interaction with HSV-1 FcR
      was not affected. However, the HSV-1 FcR, unlike human FcR, discriminates between
      human IgG1 allotypes, being sensitive to changes at positions 214 (CH1) and
      356/358 (CH3), away from its proposed binding site at the CH2-CH3 interface. The
      biological consequences are not known but this is the first evidence of a major
      functional difference between IgG1 allotypes.

PMID- 12196123
TI  - Troybodies and pepbodies.
AB  - All antibodies (Abs) with effector function are produced in mammalian cells,
      whereas bacterial production is restricted to smaller targeting fragments (scFv
      and Fab) without effector functions. In this project, we isolated different
      peptides that bind one of several Ab effector molecules. We have developed
      bacterial expression vectors for direct cloning of these peptides as fusions to
      scFv and Fab, and have obtained targeting fragments that also have the ability to
      bind Ab effector molecules. Some of these fusions (pepbodies) may also initiate
      Ab effector functions. We have also genetically inserted T-cell epitopes into Abs
      with specificity for antigen-presenting cell (APC) surface molecules to target
      the Ab-T-cell epitope fusions (Troybodies) to APCs. The approach is to exchange
      loops in Ig constant domains with single copies of well-defined T-cell epitopes.
      We have shown that a number of such T-cell epitopes are loaded on to MHC class II
      on APCs and are presented to specific T-cells. An increase in T-cell activation
      of up to four orders of magnitude is achieved compared with synthetic peptide.
      Our current goal is to identify all the loops in all Ig constant domains that may
      be loaded with T-cell epitopes to produce a multi-vaccine.

PMID- 12196124
TI  - Bispecific antibodies targeting cancer cells.
AB  - In recent years, antibody therapy has become a new treatment modality for tumour
      patients, although the majority of responses are only partial and not long
      lasting. Based on evidence that effector-cell-mediated mechanisms significantly
      contribute to antibody efficacy in vivo, several approaches are currently pursued
      to improve the interaction between Fc receptor-expressing effector cells and
      tumour target antigens. These approaches include application of Fc receptor
      directed bispecific antibodies, which contain one specificity for a tumour
      related antigen and another for a cytotoxic Fc receptor on immune effector cells.
      Thereby, bispecific antibodies selectively engage cytotoxic trigger molecules on
      killer cells, avoiding, for example, interaction with inhibitory Fc receptors. In
      vitro, chemically linked bispecific antibodies directed against the Fc gamma
      receptors Fc gamma RIII (CD16) and Fc gamma RI (CD64), and the Fc alpha receptor
      Fc alpha RI (CD89), were significantly more effective than conventional IgG
      antibodies. Recent animal studies confirmed the therapeutic potential of these
      constructs. However, results from clinical trials have been less promising so far
      and have revealed clear limitations of these molecules, such as short plasma half
      lives compared with conventional antibodies. In this review, we briefly summarize
      the scientific background for bispecific antibodies, and describe the rationale
      for the generation of novel recombinant molecules. These constructs may allow us
      to more specifically tailor pharmacokinetic properties to the demands of clinical
      applications.

PMID- 12196125
TI  - Formatting antibody fragments to mediate specific therapeutic functions.
AB  - Monoclonal antibodies are increasingly being used as therapeutic agents in a wide
      range of indications, including oncology, inflammation and infectious disease. In
      most cases the basis of the therapeutic function is the high degree of
      specificity and affinity the antibody-based drug has for its target antigen.
      However, the mechanism of action (MOA), the way the drug takes advantage of this
      specificity to mediate a therapeutic effect, varies considerably from drug to
      drug. Three basic potential categories of MOAs exist: antagonists, agonists and
      specific delivery mechanisms to target an active function to a particular cell
      type. The latter functions include selective cell killing, based on Fc-mediated
      events, recruitment of effector cells, and drug or radioisotope delivery. The
      majority of these mechanisms are not necessarily optimally mediated by an IgG
      structure; clearly, in the case of antibody-dependent cellular cytotoxicity or
      complement-mediated lysis, Fc is required. However, Fab fragments (the fragment
      comprising one antigen-binding arm of the Y-shaped IgG molecule) can be formatted
      to mediate most mechanisms and have the advantage that valency and half-life can
      be controlled to simplify the drug and address only the mechanism required.
      Moreover, Fab fragments can be produced in microbial expression systems which
      address manufacturing issues such as scale of supply and cost of goods.

PMID- 12196126
TI  - Amino acid sequence requirements in the human IgA1 hinge for cleavage by
      streptococcal IgA1 proteases.
AB  - All the IgA1 proteases of the different pathogenic species of Streptococcus
      cleave the hinge of the alpha chain of human IgA1 only at one proline-threonine
      peptide bond. In order to study the importance of these amino acids for cleavage,
      several hinge mutant recombinant IgA1 antibodies were constructed. The mutations
      were found to be without major effect upon the structure or functional abilities
      of the antibodies. However, they had a major effect upon their sensitivity to
      cleavage by some of the IgA1 proteases.

PMID- 12196127
TI  - Targeted cytokine delivery to neuroblastoma.
AB  - The aim of this study was to construct a fusion protein from the cytokine
      granulocyte/macrophage colony-stimulating factor (GM-CSF) and a single-chain Fv
      fragment (scFv D29) and to investigate its potential to activate cells of the
      immune system against neuroblastoma cells expressing neural cell adhesion
      molecule (NCAM). Mammalian cell expression of the scFv D29-GM-CSF fusion protein
      was compared using a number of vectors, including retroviral and adenoviral
      vectors. The resultant fusion protein, expressed by HeLa cells, was found by
      ELISA to bind immobilized recombinant NCAM. Moreover, FACS analysis confirmed
      binding to the human neuroblastoma cell line SKNBE and a murine neuroblastoma
      cell line engineered to express the glycosylphosphatidylinositol form of human
      NCAM (N2A-rKNIE). The fusion protein was also found to stimulate the
      proliferation of the FDC-P1 haemopoietic cell line, which is dependent on GM-CSF
      (or interleukin 3) for continued growth. In vitro clonogenic assays indicated
      that scFv-GM-CSF could selectively induce growth inhibition of SKNBE cells by
      murine lymphoid cells.

PMID- 12196128
TI  - Examining the structure of the mature amyloid fibril.
AB  - The pathogenesis of the group of diseases known collectively as the amyloidoses
      is characterized by the deposition of insoluble amyloid fibrils. These are
      straight, unbranching structures about 70-120 A (1 A=0.1 nm) in diameter and of
      indeterminate length formed by the self-assembly of a diverse group of normally
      soluble proteins. Knowledge of the structure of these fibrils is necessary for
      the understanding of their abnormal assembly and deposition, possibly leading to
      the rational design of therapeutic agents for their prevention or disaggregation.
      Structural elucidation is impeded by fibril insolubility and inability to
      crystallize, thus preventing the use of X-ray crystallography and solution NMR.
      CD, Fourier-transform infrared spectroscopy and light scattering have been used
      in the study of the mechanism of fibril formation. This review concentrates on
      the structural information about the final, mature fibril and in particular the
      complementary techniques of cryo-electron microscopy, solid-state NMR and X-ray
      fibre diffraction.

PMID- 12196129
TI  - Cholesterol and Alzheimer's disease.
AB  - Accumulation of a 40-42-amino acid peptide, termed amyloid-beta peptide (A beta),
      is associated with Alzheimer's disease (AD), and identifying medicines that
      inhibit A beta could help patients with AD. Recent evidence suggests that a class
      of medicines that lower cholesterol by blocking the enzyme 3-hydroxy-3
      methylglutaryl-CoA reductase (HMG-CoA reductase), termed statins, can inhibit A
      beta production. Increasing evidence suggests that the enzymes that generate A
      beta function best in a high-cholesterol environment, which might explain why
      reducing cholesterol would inhibit A beta production. Studies using both neurons
      and peripheral cells show that reducing cellular cholesterol levels, by stripping
      off the cholesterol with methyl-beta-cyclodextrin or by treating the cells with
      HMG-CoA reductase inhibitors, decreases A beta production. Studies performed on
      animal models and on humans concur with these results. In humans, lovastatin, an
      HMG-CoA reductase inhibitor, has been shown to reduce A beta levels in blood of
      patients by up to 40%. The putative role of A beta in AD raises the possibility
      that treating patients with statins might lower A beta, and thereby either delay
      the occurrence of AD or retard the progression of AD. Two large retrospective
      studies support this hypothesis. Both studies suggest that patients taking
      statins had an approx. 70% lower risk of developing AD. Since statins are widely
      used by doctors, their ability to reduce A beta offers a putative therapeutic
      strategy for treating AD by using medicines that have already been proved safe to
      use in humans.

PMID- 12196130
TI  - Memapsin 2 (beta-secretase) as a therapeutic target.
AB  - As beta-secretase, memapsin 2 cleaves amyloid-beta precursor protein, which leads
      ultimately to the onset of Alzheimer's disease. As such, memapsin 2 is an
      excellent target of inhibitor drugs for the treatment of this disease. Here we
      describe the tools for memapsin 2 inhibitor design that have been developed and
      results from the structure-based inhibitor design. Strategy for the design of
      memapsin 2 inhibitors with pharmaceutical potential is also discussed.

PMID- 12196131
TI  - Gamma-secretase inhibition.
AB  - Development of Alzheimer's disease (AD) pathology appears to be causally related
      to age-dependent changes in the metabolism of the amyloid-beta peptide (A beta),
      leading to its enhanced aggregation and deposition. gamma-Secretase is a crucial
      enzyme for the generation of A beta from the amyloid-beta precursor protein and
      thus represents a valid potential therapeutic target for the treatment or
      prevention of AD. Enzyme activity has been shown to be dependent on the
      expression of presenilins and the identification of inhibitors containing
      transition-state analogue mimics, together with mutagenesis and knockout studies,
      confirms that presenilins may provide at least a component of the catalytic site
      for this putative aspartyl protease. Considerable effort has been expended to
      identify compounds which specifically reduce gamma-secretase activity in the
      central nervous system, and those with the appropriate properties are being
      utilized in on-going proof-of-concept studies in animals and humans, to determine
      the extent and duration of gamma-secretase inhibition required to elicit
      therapeutic benefits. gamma-Secretase-mediated substrate cleavage appears to fall
      into the category of 'regulated intramembrane proteolysis'. By virtue of its
      mechanistic similarities, the effects of gamma-secretase inhibitors on
      proteolysis and signalling through other substrates, such as Notch, has to be
      determined carefully, since this is likely to impact on the clinically safe dose
      of these compounds.

PMID- 12196133
TI  - Amyloid fibril formation by human stefin B: influence of the initial pH-induced
      intermediate state.
AB  - The amyloid fibril field is briefly described, with some stress put on
      differences between various proteins and possible role for domain swapping. In
      the main body of the text, first, a short review is given of the folding
      properties of both human stefins, alpha/beta-type globular proteins of 53%
      identity with a known three-dimensional fold. Second, in vitro study of amyloid
      fibril formation by human stefin B (type I cystatin) is described. Solvents of pH
      4.8 and pH 3.3 with and without 2,2,2-trifluoroethanol (TFE) were probed, as it
      has been shown previously that stefin B forms acid intermediates, a native-like
      and molten globule intermediate, respectively. The kinetics of fibrillation were
      measured by thioflavin T fluorescence and CD. At pH 3.3, the protein is initially
      in the molten globule state. The fibrillation is faster than at pH 4.8; however,
      there is more aggregation observed. On adding TFE at each pH, the fibril
      formation is further accelerated.

PMID- 12196132
TI  - Inhibition of toxicity and protofibril formation in the amyloid-beta peptide
      beta(25-35) using N-methylated derivatives.
AB  - Beta (25-35) is a fragment of beta-amyloid that retains its wild-type properties.
      N-methylated derivatives of beta(25-35) can block hydrogen bonding on the outer
      edge of the assembling amyloid, so preventing the aggregation and inhibiting the
      toxicity of the wild-type peptide. The effects are assayed by Congo Red and
      thioflavin T binding, electron microscopy and an MTT [3-(4,5-dimethylthiazol-2
      yl)-2,5-diphenyltetrazolium bromide] toxicity assay. N-methyl-Gly-25 has similar
      properties to the wild- type, while five other methylation sites have varying
      effects on prefolded fibrils and fibril assembly. In particular, N-methyl-Gly-33
      is able to completely prevent fibril assembly and reduces the toxicity of
      prefolded amyloid. With N-methyl-Leu-34 the fibril morphology is altered and
      toxicity reduced. A preliminary study of beta(25-35) structure in aqueous
      solution was made by small-angle neutron scattering (SANS). The protofibrillar
      aggregates are best described as a disc of radius 140 A and height 53 A (1 A =
      0.1 nm), though the possibility of polydisperse aggregates cannot be ruled out.
      No aggregates form in the presence of N-methyl-Gly-33. We suggest that the use of
      N-methylated derivatives of amyloidogenic peptides and proteins could provide a
      general solution to the problem of amyloid deposition and toxicity and that SANS
      is an important technique for the direct observation of protofibril formation and
      destruction in solution.

PMID- 12196134
TI  - Glutamine repeats: structural hypotheses and neurodegeneration.
AB  - A growing number of neurodegenerative diseases are caused by expansion of CAG
      trinucleotide repeats coding for polyglutamine. The presence of intranuclear
      inclusions in the affected neuronal cells has suggested a mechanism for
      pathogenesis based on protein misfolding and aggregation. Detailed understanding
      of these phenomena is therefore crucial in order to rationalize different phases
      of the diseases. In the past decade, a few studies have focused on the structural
      properties of polyglutamine and on the molecular bases of the aggregation
      process. Most of these studies have been performed on polyglutamine peptides and
      protein models. Only one report is currently available on the characterization of
      a full-length polyglutamine protein. The structural hypotheses resulting from
      these studies are reviewed here.

PMID- 12196135
TI  - Amyloid-beta oligomers: their production, toxicity and therapeutic inhibition.
AB  - Despite extensive genetic and animal modelling data that support a central role
      for the amyloid beta-protein (A beta) in the genesis of Alzheimer's disease, the
      specific form(s) of A beta which causes injury to neurons in vivo has not been
      identified. In the present study, we examine the importance of soluble, pre
      fibrillar assemblies of A beta as mediators of neurotoxicity. Specifically, we
      review the role of cell-derived SDS-stable oligomers, their blocking of
      hippocampal long-term potentiation in vivo and the finding that this blocking can
      be prevented by prior treatment of oligomer-producing cells with gamma-secretase
      inhibitors.

PMID- 12196137
TI  - Aggregation and neurotoxicity of alpha-synuclein and related peptides.
AB  - Fibrillar deposits of alpha-synuclein occur in several neurodegenerative
      diseases. Two mutant forms of alpha-synuclein have been associated with early
      onset Parkinson's disease, and a fragment has been identified as the non-amyloid
      beta peptide component of Alzheimer's disease amyloid (NAC). Upon aging,
      solutions of alpha-synuclein and NAC change conformation to beta-sheet,
      detectable by CD spectroscopy, and form oligomers that deposit as amyloid-like
      fibrils, detectable by electron microscopy. These aged peptides are also
      neurotoxic. Experiments on fragments of NAC have enabled the region of NAC
      responsible for its aggregation and toxicity to be identified. NAC(8-18) is the
      smallest fragment that aggregates, as indicated by the concentration of peptide
      remaining in solution after 3 days, and forms fibrils, as determined by electron
      microscopy. Fragments NAC(8-18) and NAC(8-16) are toxic, whereas NAC(12-18),
      NAC(9-16) and NAC(8-15) are not. Hence residues 8-16 of NAC comprise the region
      crucial for toxicity. Toxicity induced by alpha-synuclein, NAC and NAC(1-18)
      oligomers occurs via an apoptotic mechanism, possibly initiated by oxidative
      damage, since these peptides liberate hydroxyl radicals in the presence of iron.
      Molecules with anti-aggregational and/or antioxidant properties may therefore be
      potential therapeutic agents.

PMID- 12196136
TI  - Properties of neurotoxic peptides related to the BRI gene.
AB  - Mutations in the BRI gene are thought to cause dementias in members of families.
      The clinical symptoms are similar to those of Alzheimer's disease, but with
      additional ocular and hearing deficits, and spasticity. The mutations lead to the
      release of the 34-residue peptides, ABri and ADan, in the brains of afflicted
      individuals. We have synthesized the peptides in their straight-chain and
      oxidized cyclic forms and shown that the oxidized form of ABri and reduced form
      of ADan are toxic to human neuronal cell lines in culture. Neurotoxicity
      correlates with the extent of formation of SDS-stable non-fibrillar low-molecular
      mass oligomers (SSNFOs).

PMID- 12196138
TI  - Factors affecting interactions between prion protein isoforms.
AB  - Interactions between normal, protease-sensitive prion protein (PrP-sen or PrP(C))
      and its protease-resistant isoform (PrP-res or PrP(Sc)) are critical in
      transmissible spongiform encephalopathy (TSE) diseases. To investigate the
      propagation of PrP-res between cells we tested whether PrP-res in scrapie brain
      microsomes can induce the conversion of PrP-sen to PrP-res if the PrP-sen is
      bound to uninfected raft membranes. Surprisingly, no conversion was observed
      unless the microsomal and raft membranes were fused or PrP-sen was released from
      raft membranes. These results suggest that the propagation of infection between
      cells requires transfer of PrP-res into the membranes of the recipient cell. To
      assess potential cofactors in PrP conversion, we used cell-free PrP conversion
      assays to show that heparan sulphate can stimulate PrP-res formation, supporting
      the idea that endogenous sulphated glycosaminoglycans can act as important
      cofactors or modulators of PrP-res formation in vivo. In an effort to develop
      therapeutics, the antimalarial drug quinacrine was identified as an inhibitor of
      PrP-res formation in scrapie-infected cell cultures. Confirmation of the latter
      result by others has led to the initiation of human clinical trials as a
      treatment for Creutzfeldt-Jakob disease. PrP-res formation can also be inhibited
      using a variety of other types of small molecule, specific synthetic PrP
      peptides, and an antiserum directed at the C-terminus of PrP-sen. The latter
      results help to localize the sites of interaction between PrP-sen and PrP-res.
      Disruption of those interactions with antibodies or peptidomimetic drugs may be
      an attractive therapeutic strategy. The likelihood that PrP-res inhibitors can
      rid TSE-infected tissues of PrP-res would presumably be enhanced if PrP-res
      formation were reversible. However, our attempts to measure dissociation of PrP
      sen from PrP-res have failed under non-denaturing conditions. Finally, we have
      attempted to induce the spontaneous conversion of PrP-sen into PrP-res using low
      concentrations of detergents. A conformational conversion from alpha-helical
      monomers into high-beta-sheet aggregates and fibrils was induced by low
      concentrations of the detergent sarkosyl; however, the aggregates had neither
      infectivity nor the characteristic protease-resistance ofPrP-res.

PMID- 12196139
TI  - Altering prion replication for therapy and diagnosis of transmissible spongiform
      encephalopathies.
AB  - Transmissible spongiform encephalopathies, also known as prion-related diseases,
      are a group of fatal neurodegenerative disorders associated with the misfolding
      of the prion protein. In this article, the potential use of the principles of
      prion replication to develop novel therapeutic and diagnostic strategies for
      these devastating diseases are described.

PMID- 12196141
TI  - Structure and function of glutamyl-tRNA reductase involved in 5-aminolaevulinic
      acid formation.
AB  - In most bacteria, in archaea and in plants, the general precursor of all
      tetrapyrroles, 5-aminolaevulinic acid, is formed by two enzymes. The initial
      substrate, glutamyl-tRNA, is reduced by NADPH-dependent glutamyl-tRNA reductase
      to form glutamate 1-semialdehyde. The aldehyde is subsequently transaminated by
      glutamate-1-semialdehyde 2,1-aminomutase to yield 5-aminolaevulinic acid. The
      enzymic mechanism and the solved crystal structure of Methanopyrrus kandleri
      glutamyl-tRNA reductase are described. A pathway for metabolic channelling of the
      reactive aldehyde between glutamyl-tRNA reductase and the aminomutase is
      proposed.

PMID- 12196140
TI  - Therapeutics in Alzheimer's and prion diseases.
AB  - There is increasing recognition that numerous neurodegenerative conditions have
      the same underlying pathogenetic mechanism, namely a change in protein
      conformation, where the beta-sheet content is increased. In Alzheimer's disease,
      amyloid deposition in the form of neuritic plaques and congophilic angiopathy is
      driven by the conversion of normal soluble amyloid-beta peptide (sA beta) to A
      beta plaques; while in the prionoses the critical event is the conversion of
      normal prion protein, PrP(C), to the disease-associated form, PrP(Sc). This
      common theme in the pathogenesis of these disorders and the extracellular
      localization of the accumulating abnormal protein make them highly amenable to
      therapeutic approaches based on experimental manipulation of protein conformation
      and clearance. A number of different approaches under current development include
      drugs which affect the processing of the precursor proteins drugs the clearance
      of the amyloidogenic protein, and which inhibit or prevent the conformation
      change and immunological approaches. Particularly interesting are compounds
      termed 'beta-sheet breakers' that directly target the abnormal conformational
      change both for A beta- and PrP(Sc)-related deposits. In addition, immune system
      activation can serve as beta-sheet breakers and/or to increase the clearance of
      the disease-associated proteins. These conformation-based approaches appear to
      hold the best promise for therapies for this devastating group of disorders.

PMID- 12196142
TI  - 5-Aminolaevulinic acid dehydratase: metals, mutants and mechanism.
AB  - 5-Aminolaevulinic acid dehydratase catalyses the formation of porphobilinogen
      from two molecules of 5-aminolaevulinic acid. The studies described highlight the
      importance of a bivalent metal ion and two active-site lysine residues for the
      functioning of 5-aminolaevulinic acid dehydratase. Dehydratases fall into two
      main categories: zinc-dependent enzymes and magnesium-dependent enzymes.
      Mutations that introduced zinc-binding ligands into a magnesium-dependent enzyme
      conferred an absolute requirement for zinc. Mutagenesis of lysine residues 247
      and 195 in the Escherichia coli enzyme lead to dramatic effects on enzyme
      activity, with lysine 247 being absolutely essential. Mutation of either lysine
      247 or 195 to cysteine, and treatment of the mutant enzyme with 2-bromethylamine,
      resulted in the recovery of substantial enzyme activity. The effects of the site
      directed alkylating inhibitor, 5-chlorolaevulinic acid, and 4,7-dioxosebacic
      acid, a putative intermediate analogue, were investigated by X-ray
      crystallography. These inhibitors reacted with both active-site lysine residues.
      The role of these two lysine residues in the enzyme mechanism is discussed.

PMID- 12196143
TI  - Terminal steps of haem biosynthesis.
AB  - The terminal three steps in haem biosynthesis are the oxidative decarboxylation
      of coproporphyrinogen III to protoporphyrinogen IX, followed by the six-electron
      oxidation of protoporphyrinogen to protoporphyrin IX, and finally the insertion
      of ferrous iron to form haem. Interestingly, Nature has evolved distinct enzymic
      machinery to deal with the antepenultimate (coproporphyrinogen oxidase) and
      penultimate (protoporphyrinogen oxidase) steps for aerobic compared with
      anaerobic organisms. The terminal step is catalysed by the enzyme ferrochelatase.
      This enzyme is clearly conserved with regard to a small set of essential
      catalytic residues, but varies significantly with regard to size, subunit
      composition, cellular location and the presence or absence of a [2Fe-2S] cluster.
      Coproporphyrinogen oxidase and protoporphyrinogen oxidase are reviewed with
      regard to their enzymic and physical characteristics. Ferrochelatase, which is
      the best characterized of these three enzymes, will be described with particular
      emphasis paid to what has been learned from the crystal structure of the Bacillus
      subtilis and human enzymes.

PMID- 12196144
TI  - Structural diversity in metal ion chelation and the structure of uroporphyrinogen
      III synthase.
AB  - All tetrapyrroles are synthesized through a branched pathway, and although each
      tetrapyrrole receives unique modifications around the ring periphery, they all
      share the unifying feature of a central metal ion. Each pathway maintains a
      unique metal ion chelatase, and several tertiary structures have been determined,
      including those of the protoporphyrin ferrochelatase from both human and Bacillus
      subtilus, and the cobalt chelatase CbiK. These enzymes exhibit strong structural
      similarity and appear to function by a similar mechanism. Met8p, from
      Saccharomyces cerevisiae, catalyses ferrochelation during the synthesis of
      sirohaem, and the structure reveals a novel chelatase architecture whereby both
      ferrochelation and NAD(+)-dependent dehydrogenation take place in a single
      bifunctional active site. Asp-141 appears to participate in both catalytic
      reactions. The final common biosynthetic step in tetrapyrrole biosynthesis is the
      generation of uroporphyrinogen by uroporphyrinogen III synthase, whereby the D
      ring of hydroxymethylbilane is flipped during ring closure to generate the
      asymmetrical structure of uroporphyrinogen III. The recently derived structure of
      uroporphyrinogen III synthase reveals a bi-lobed structure in which the active
      site lies between the domains.

PMID- 12196145
TI  - Site-directed mutagenesis of Tyr-189 and Lys-193 in NADPH: protochlorophyllide
      oxidoreductase from Synechocystis.
AB  - NADPH:protochlorophyllide oxidoreductase (POR) catalyses the light-dependent
      reduction of protochlorophyllide to chlorophyllide, a key regulatory reaction in
      the chlorophyll biosynthetic pathway. Sequence comparisons have revealed that POR
      is a member of the short-chain alcohol dehydrogenase family of enzymes. A
      tyrosine and a lysine residue are conserved throughout all members of this
      family, and are proposed to be within the active site. This present study
      describes how site-directed mutagenesis has been used to change Tyr-189 to Phe
      and Lys-193 to Arg in the Synechocystis POR enzyme. The mutant enzymes were
      produced with a His tag in Escherichia coli and subsequently purified on a Ni(2+)
      affinity column. The two mutations resulted in inactive enzymes, indicating that
      both residues are crucial for activity. The K(d) value for NADPH binding to the
      K193R mutant was significantly higher than for the wild-type enzyme, suggesting
      that the affinity for NADPH has also been reduced.

PMID- 12196146
TI  - Making light of it: the role of plant haem oxygenases in phytochrome chromophore
      synthesis.
AB  - The haem oxygenase (HO) enzyme catalyses the oxidation of haem to biliverdin IX
      alpha, CO and Fe(2+), and performs a wide variety of roles in Nature, including
      degradation of haem from haemoglobin, iron acquisition and phycobilin
      biosynthesis. In plants, HOs are required for the synthesis of the chromophore of
      the phytochrome family of photoreceptors. There are four HO genes in the
      Arabidopsis genome. Analysis of a mutant deficient in HO1 (the hy1 mutant) has
      demonstrated that this plastid-localized protein is the major HO in the
      phytochrome chromophore synthesis pathway. HO2 may also have a minor role in this
      pathway, but our understanding of the divergent roles of this small gene family
      is still far from complete.

PMID- 12196147
TI  - Production of cobalamin and sirohaem in Bacillus megaterium: an investigation
      into the role of the branchpoint chelatases sirohydrochlorin ferrochelatase
      (SirB) and sirohydrochlorin cobalt chelatase (CbiX).
AB  - One of the four operons required for cobalamin biosynthesis in Bacillus
      megaterium is also associated with sirohaem synthesis, and contains three genes,
      sirA, sirB and sirC. By undertaking functional complementation experiments and in
      vitro assays using recombinantly produced enzymes, we have been able to
      demonstrate that (1) SirA acts as a uroporphyrinogen III methyltransferase,
      transforming uroporphyrinogen III into precorrin-2, (2) SirC acts as an NAD(+)
      dehydrogenase, responsible for the oxidation of precorrin-2 into
      sirohydrochlorin, and (3) SirB acts as a ferrochelatase, responsible for the
      insertion of a ferrous ion into sirohydrochlorin to give sirohaem. Comparative
      sequence analysis reveals that the primary structure of SirB is highly similar to
      that of the cobalt chelatase involved in cobalamin biosynthesis in Bacillus
      megaterium, CbiX, with the exception that CbiX contains a C-terminal histidine
      rich motif. Surprisingly, CbiX has been shown (using EPR) to contain a 4Fe-4S
      centre, a redox centre that is absent from SirB.

PMID- 12196148
TI  - Biosynthesis of cobalamin (vitamin B(12)).
AB  - The biosynthesis of vitamin B(12) is summarized, emphasizing the differences
      observed between the aerobic and anaerobic pathways. The biosynthetic route to
      adenosylcobalamin from its five-carbon precursor, 5-aminolaevulinic acid, can be
      divided into three sections: (1) the biosynthesis of uroporphyrinogen III from 5
      aminolaevulinic acid, which is common to both pathways; (2) the conversion of
      uroporphyrinogen III into the ring-contracted, deacylated intermediate precorrin
      6 or cobalt-precorrin 6, which includes the primary differences between the two
      pathways; and (3) the transformation of this intermediate to form
      adenosylcobalamin.

PMID- 12196149
TI  - Controlling the reactivity of radical intermediates by coenzyme B(12)-dependent
      methylmalonyl-CoA mutase.
AB  - Adenosylcobalamin or coenzyme B(12)-dependent enzymes are members of the still
      relatively small group of radical enzymes and catalyse 1,2-rearrangement
      reactions. A member of this family is methylmalonyl-CoA mutase, which catalyses
      the isomerization of methylmalonyl-CoA to succinyl-CoA and, unlike the others, is
      present in both bacteria and animals. Enzymes that catalyse some of the most
      chemically challenging reactions are the ones that tend to deploy radical
      chemistry. The use of radical intermediates in an active site lined with amino
      acid side chains that threaten to extinguish the reaction by presenting
      alternative groups for abstraction poses the conundrum of how the enzymes control
      their reactivity. In this review, insights into this issue that have emerged from
      kinetic, mutagenesis and structural studies are described for methylmalonyl-CoA
      mutase.

PMID- 12196150
TI  - Unravelling chlorophyll catabolism in higher plants.
AB  - Chlorophyll metabolism is probably the most visible manifestation of life. In
      spite of this, chlorophyll catabolism has remained something of a mystery until
      about 10 years ago. At that time, the first non-green tetrapyrrolic chlorophyll
      breakdown products from higher plants were discovered, and the structure of the
      first one of them was elucidated by modern spectroscopic methods. In the
      meantime, the essential structural features of chlorophyll catabolites and some
      of the biochemistry of chlorophyll breakdown in higher plants have been
      uncovered, as outlined in this article.

PMID- 12196151
TI  - Haem degradation in animals and plants.
AB  - Two enzyme systems have evolved for the reduction of linear tetrapyrroles: one
      family, found in plants, algae and cyanobacteria, uses ferredoxin and catalyses
      the reduction of the terminal pyrrole rings (A and D) and one of the vinyl side
      chains to form various light-harvesting and light-sensing chromophores. The other
      group (biliverdin reductases A and B) utilize NAD(P)H and catalyse reduction at
      C10 (hydride addition) to form the 'bile' pigments bilirubin-IX alpha and
      bilirubin-IX.

PMID- 12196152
TI  - Cytochrome c maturation: a complex pathway for a simple task?
AB  - Post-translational maturation of c-type cytochromes involves covalent attachment
      of haem to the apocytochrome polypeptide by two thioether bonds. In bacteria,
      haem attachment occurs in the periplasm, after the separate translocation of haem
      and the polypeptide across the cytoplasmic membrane. In Escherichia coli,
      delivery and attachment of the cofactor requires eight or nine specific proteins,
      which are believed to be organized in a membrane protein complex. After transport
      across the membrane, haem is attached covalently to the haem chaperone CcmE in an
      unusual way at a single histidine residue. However, haem binding to CcmE is
      transient and is succeeded by a further transfer to apocytochrome c. Both haem
      binding to and release from CcmE involve integral membrane proteins, CcmC and
      CcmF respectively, which carry a conserved tryptophan-rich motif in a periplasmic
      domain. Apocytochrome c polypeptides are synthesized as precursors and reach the
      periplasm by sec-dependent translocation. There they are prepared for haem
      binding by reduction of the cysteine residues in the motif Cys-Xaa-Xaa-Cys-His,
      which is characteristic of such proteins. This reduction is achieved in a thio
      reduction pathway, whereby electrons are passed from cytoplasmic thioredoxin to
      the transmembrane protein DsbD, across the membrane, and on to the specific
      reductases CcmG/CcmH. The merging of the haem delivery and the thio-reduction
      pathways leads to the stereospecific insertion of haem into various type c
      cytochromes.

PMID- 12196153
TI  - Novel domain packing in the crystal structure of a thiosulphate-oxidizing enzyme.
AB  - A key component of the oxidative biogeochemical sulphur cycle involves the
      utilization by bacteria of reduced inorganic sulphur compounds as electron donors
      to photosynthetic or respiratory electron transport chains. The SoxAX protein of
      the photosynthetic bacterium Rhodovulum sulfidophilum is a heterodimeric c-type
      cytochrome that is involved in the oxidation of thiosulphate and sulphide. The
      recently solved crystal structure of the SoxAX complex represents the first
      structurally characterized example of a productive electron transfer complex
      between haemoproteins where both partners adopt the c-type cytochrome fold. The
      packing of c-type cytochrome domains both within SoxA and at the interface
      between the subunits of the complex has been compared with other examples and
      found to be unique.

PMID- 12196154
TI  - Current understanding of the function of magnesium chelatase.
AB  - Despite the global significance of chlorophylls and other modified tetrapyrroles,
      many aspects of their biosynthetic pathways are poorly understood. A key enzyme
      at the branch point between the haem and chlorophyll pathways, magnesium
      chelatase, couples the free energy of ATP hydrolysis to the insertion of
      magnesium into porphyrin, a process that is likely to be mediated through protein
      conformational changes. Conclusions from recent structural and functional studies
      of individual subunits are combined to provide a mechanistic outline of the full
      magnesium chelatase complex. Gathering further information presents a
      considerable challenge, and recent steps towards this goal will be introduced.

PMID- 12196155
TI  - Cobalamin (vitamin B(12)) biosynthesis in Rhodobacter capsulatus.
AB  - In Rhodobacter capsulatus, cobalamin biosynthesis has been shown to occur when
      the bacteria are grown either aerobically or anaerobically. However, a comparison
      of the main cobalamin biosynthetic operon found within R. capsulatus would
      suggest that the encoded proteins belong to the oxygen-dependent pathway for
      cobalamin biosynthesis, although, significantly, no homologue of the essential
      mono-oxygenase CobG has yet been detected. Nonetheless, within this main cob
      operon is found a large open reading frame termed orf663 that is not found in any
      other cobalamin biosynthetic operon. When overproduced in Escherichia coli,
      orf663 was found to encode a 90 kDa integral membrane protein. Some of this
      protein is cleaved within E. coli to give a soluble N-terminal region that can
      easily be purified and yields a 50 kDa flavoprotein. When expressed in harness
      with the genes for precorrin-3a synthesis, ORF663 appears to mediate the
      transformation of precorrin-3a into a new chromophoric compound. Another open
      reading frame in close proximity to orf663 is termed orf647, and was found to
      encode a 2Fe-2S ferredoxin-like protein. We suggest that these two proteins may
      provide an alternative oxygen-independent mechanism for ring contraction within
      R. capsulatus.

PMID- 12196156
TI  - Pentahaem cytochrome c nitrite reductase: reaction with hydroxylamine, a
      potential reaction intermediate and substrate.
AB  - The pentahaem enzyme cytochrome c nitrite reductase catalyses the reduction of
      nitrite to ammonia, a key reaction in the biological nitrogen cycle. The enzyme
      can also transform nitrogen monoxide and hydroxylamine, two potential bound
      reaction intermediates, into ammonia. Structural and mechanistic aspects of the
      multihaem enzyme are discussed in comparison with hydroxylamine oxidoreductase, a
      trimeric protein with eight haem molecules per subunit.

PMID- 12196157
TI  - Cytochrome cbb(3) oxidase and bacterial microaerobic metabolism.
AB  - Cytochrome cbb(3) oxidase is a member of the haem-copper oxidase superfamily. It
      is characterized by its high oxygen affinity, while retaining the ability to pump
      protons. These attributes are central to its proposed role in bacterial
      microaerobic metabolism. Recent spectroscopic characterization of both the
      cytochrome cbb(3) oxidase complex from Pseudomonas stutzeri and the dihaem ccoP
      subunit expressed separately in Escherichia coli has revealed the presence of a
      low-spin His/His co-ordinated c-type cytochrome. The low midpoint reduction
      potential of this haem (E(m)<+100 mV), together with its unexpected ability to
      bind CO in the reduced state at the expense of the distal histidine ligand,
      raises questions about the role of the ccoP subunit in the delivery of electrons
      to the active site.

PMID- 12196158
TI  - The membrane-bound tetrahaem c-type cytochrome CymA interacts directly with the
      soluble fumarate reductase in Shewanella.
AB  - Shewanella spp. demonstrate great variability in the use of terminal electron
      acceptors in anaerobic respiration; these include nitrate, fumarate, DMSO,
      trimethylamine oxide, sulphur compounds and metal oxides. These pathways open up
      possible applications in bioremediation. The wide variety of respiratory
      substrates for Shewanella is correlated with the evolution of several multi-haem
      membrane-bound, periplasmic and outer-membrane c-type cytochromes. The 21 kDa c
      type cytochrome CymA of the freshwater strain Shewanella oneidensis MR-1 has an N
      terminal membrane anchor and a globular tetrahaem periplasmic domain. According
      to sequence alignments, CymA is a member of the NapC/NirT family. This family of
      redox proteins is responsible for electron transfer from the quinone pool to
      periplasmic and outer-membrane-bound reductases. Prior investigations have shown
      that the absence of CymA results in loss of the ability to respire with Fe(III),
      fumarate and nitrate, indicating that CymA is involved in electron transfer to
      several terminal reductases. Here we describe the expression, purification and
      characterization of a soluble, truncated CymA ('CymA). Potentiometric studies
      suggest that there are two pairs of haems with potentials of -175 and -261 mV and
      that 'CymA is an efficient electron donor for the soluble fumarate reductase,
      flavocytochrome c(3).

PMID- 12196159
TI  - Comparison between the nitric oxide reductase family and its aerobic relatives,
      the cytochrome oxidases.
AB  - The denitrification pathway has been studied in the hyperthermophilic archaeon
      Pyrobaculum aerophilum. In contrast with Gram-negative bacteria, all four
      denitrification enzymes are membrane-bound. P. aerophilum is also the only
      denitrifyer identified so far in which menaquinol is the electron donor to all
      four denitrification reductases. The NO reductase (NOR) of P. aerophilum belongs
      to the superfamily of haem-copper oxidases and is of the qNOR (quinol-dependent)
      type. Three types of NOR have been purified so far: cNOR (cytochrome
      c/pseudoazurin-dependent), qNOR and qCu(A)NOR (qNOR that contains Cu(A) at the
      electron entry site). It is proposed that the NORs and the various cytochrome
      oxidases have evolved by modular evolution, in view of the structure of their
      electron donor sites. qNOR is further proposed to be the ancestor of all NORs and
      cytochrome oxidases belonging to the superfamily of haem-copper oxidases.

PMID- 12196160
TI  - Molecular and atomic analysis of uranium complexes formed by three eco-types of
      Acidithiobacillus ferrooxidans.
AB  - A combination of EXAFS, transmission electron microscopy and energy-dispersive X
      ray was used to conduct a molecular and atomic analysis of the uranium complexes
      formed by Acidithiobacillus ferrooxidans. The results demonstrate that this
      bacterium accumulates uranium as phosphate compounds. We suggest that at toxic
      levels when the uranium enters the bacterial cells, A. ferrooxidans can detoxify
      and efflux this metal by a process in which its polyphosphate bodies are
      involved.

PMID- 12196161
TI  - Mechanisms of mercury bioremediation.
AB  - Mercury is one of the most toxic heavy metals, and has significant industrial and
      agricultural uses. These uses have led to severe localized mercury pollution.
      Mercury volatilization after its reduction to the metallic form by mercury
      resistant bacteria has been reported as a mechanism for mercury bioremediation
      [Brunke, Deckwer, Frischmuth, Horn, Lunsdorf, Rhode, Rohricht, Timmis and Weppen
      (1993) FEMS Microbiol. Rev. 11, 145-152; von Canstein, Timmis, Deckwer and Wagner
      Dobler (1999) Appl. Environ. Microbiol. 65, 5279-5284]. The
      reduction/volatilization system requires to be studied further, in order to
      eliminate the escape of the metallic mercury into the environment. Recently we
      have demonstrated three different mechanisms for mercury detoxification in one
      organism, Klebsiella pneumoniae M426, which may increase the capture efficiency
      of mercury.

PMID- 12196163
TI  - Biosynthesis of iron-sulphur clusters is a complex and highly conserved process.
AB  - Iron-sulphur ([Fe-S]) clusters are simple inorganic prosthetic groups that are
      contained in a variety of proteins having functions related to electron transfer,
      gene regulation, environmental sensing and substrate activation. In spite of
      their simple structures, biological [Fe-S] clusters are not formed spontaneously.
      Rather, a consortium of highly conserved proteins is required for both the
      formation of [Fe-S] clusters and their insertion into various protein partners.
      Among the [Fe-S] cluster biosynthetic proteins are included a pyridoxal phosphate
      dependent enzyme (NifS) that is involved in the activation of sulphur from l
      cysteine, and a molecular scaffold protein (NifU) upon which [Fe-S] cluster
      precursors are formed. The formation or transfer of [Fe-S] clusters appears to
      require an electron-transfer step. Another complexity is that molecular
      chaperones homologous to DnaJ and DnaK are involved in some aspect of the
      maturation of [Fe-S]-cluster-containing proteins. It appears that the basic
      biochemical features of [Fe-S] cluster formation are strongly conserved in
      Nature, since organisms from all three life Kingdoms contain the same consortium
      of homologous proteins required for [Fe-S] cluster formation that were discovered
      in the eubacteria.

PMID- 12196162
TI  - Metal insertion into NiFe-hydrogenases.
AB  - The synthesis and the insertion of the metallocentre of NiFe-hydrogenases is a
      complex process, in which seven maturation enzymes plus ATP, GTP and carbamoyl
      phosphate are involved. The review summarizes what is known about the properties
      and activities of these auxiliary proteins, and postulates a pathway along which
      maturation may take place.

PMID- 12196164
TI  - Sulfolobus aconitase, a regulator of iron metabolism?
AB  - The aconitase of Sulfolobus solfataricus, a hyperthermophilic crenarchaeon, was
      cloned and heterologously expressed in Escherichia coli. Enzymic analyses and EPR
      measurements indicated clearly that the iron-sulphur cluster of the thermophilic
      aconitase was already inserted in the mesophilic host. The enzyme was purified to
      a specific activity of approx. 44 units/mg and to 90% homogeneity. The enzymic
      parameters of the recombinant aconitase turned out to be in the same range as the
      respective values for the previously characterized native enzyme from the closely
      related S. acidocaldarius. Based on its primary sequence, the recombinant
      aconitase is closely related to bacterial A-like and to eukaryotic iron
      regulatory protein-like proteins. Specific aconitase activities in cytosolic
      extracts of S. acidocaldarius were found to be decreased markedly in iron-starved
      compared with iron-repleted cells. However, no differences in aconitase levels
      between iron-starved and iron-supplemented cells could be detected by
      immunostaining.

PMID- 12196166
TI  - Microbial siderophore-mediated transport.
AB  - Microbial iron chelates, called siderophores, are synthesized by bacteria and
      fungi in response to low iron availability in the environment. The present review
      summarizes structural details of siderophore ligands with respect to their
      transport properties. This presentation is largely centred on the occurrence and
      function of siderophores in the various bacterial and fungal genera.

PMID- 12196165
TI  - Role of proteolysis in copper homoeostasis.
AB  - The cop operon of Enterococcus hirae controls cytoplasmic copper levels. It
      encodes two copper ATPases, a repressor, and the CopZ metallochaperone.
      Transcription of these genes is induced by copper. However, at higher copper
      concentrations, CopZ is degraded by a copper-activated proteolytic activity. This
      specific proteolysis of CopZ can also be demonstrated in vitro with E. hirae
      extracts. Growth of the cells in copper increases the copper-inducible
      proteolytic activity in extracts. Zymography reveals the presence of a copper
      dependent protease in crude cell lysates. Copper-stimulated proteolysis of CopZ
      appears to play an important role in copper homoeostasis by E. hirae.

PMID- 12196167
TI  - Siderophore production by Fusarium venenatum A3/5.
AB  - Fusarium venenatum A3/5 was grown in iron-restricted batch cultures and iron
      limited chemostat cultures to determine how environmental conditions affected
      siderophore production. The specific growth rate in iron-restricted batch
      cultures was 0.22 h(-1), which was reduced to 0.12 h(-1) when no iron was added
      to the culture. D(crit) in iron-limited chemostat culture was 0.1 h(-1).
      Siderophore production was correlated with specific growth rate, with the highest
      siderophore production occurring at D=0.08 h(-1) and the lowest at D=0.03 h(-1).
      Siderophore production was greatest at pH 4.7 and was significantly reduced at
      pHs above 6.0. Siderophore production could be enhanced by providing insoluble
      iron instead of soluble iron in continuous flow cultures.

PMID- 12196168
TI  - The response to iron deprivation in Saccharomyces cerevisiae: expression of
      siderophore-based systems of iron uptake.
AB  - The budding yeast Saccharomyces cerevisiae responds to growth in limiting amounts
      of iron by activating the transcription factor Aft1p and expressing a set of
      genes that ameliorate the effects of iron deprivation. Analysis of iron-regulated
      gene expression using cDNA microarrays has revealed the set of genes controlled
      by iron and Aft1p. Many of these genes are involved in the uptake of siderophore
      bound iron from the environment. One family of genes, FIT1, FIT2 and FIT3, codes
      for mannoproteins that are incorporated into the cell wall via
      glycosylphosphatidylinositol anchors. These genes are involved in the retention
      of siderophore-iron in the cell wall. Siderophore-bound iron can be taken up into
      the cell via two genetically separable systems. One system requires the reduction
      and release of the iron from the siderophore prior to uptake by members of the
      Fre family of plasma-membrane metalloreductases. Following reduction and release
      from the siderophore, the iron is then taken up via the high-affinity ferrous
      transport system. A set of transporters that specifically recognizes siderophore
      iron chelates is also expressed under conditions of iron deprivation. These
      transporters, encoded by ARN1, ARN2/TAF1, ARN3/SIT1 and ARN4/ENB1, facilitate the
      uptake of both hydroxamate- and catecholate-type siderophores. The Arn
      transporters are expressed in intracellular vesicles that correspond to the
      endosomal compartment, which suggests that intracellular trafficking of the
      siderophore and/or its transporter may be important for uptake.

PMID- 12196170
TI  - Transferrin-mediated iron acquisition by pathogenic Neisseria.
AB  - The pathogenic Neisseria have a siderophore-independent iron-uptake system
      reliant on a direct interaction between the bacterial cell and transferrin. In
      the meningococcus this uptake system is dependent on two surface-exposed
      transferrin-binding proteins. This short account will review our current
      knowledge of the transferrin-mediated iron-acquisition system of pathogenic
      Neisseria.

PMID- 12196169
TI  - A new mechanism for membrane iron transport in Pseudomonas aeruginosa.
AB  - Various biochemical and biophysical studies have demonstrated the existence of a
      novel iron-uptake mechanism in Pseudomonas aeruginosa, different from that
      generally described for ferrichrome and ferric-enterobactin in Escherichia coli.
      This new iron-uptake mechanism involves all the proteins generally reported to be
      involved in the uptake of ferric-siderophore complexes in Gram-negative bacteria
      (i.e. the outer membrane receptor, periplasmic binding protein and ATP-binding
      cassette transporter), but differs in the behaviour of the siderophore. One of
      the key features of this process is the binding of iron-free pyoverdin to the
      outer membrane receptor FpvA in conditions of iron deficiency.

PMID- 12196171
TI  - Bipartite gating in the outer membrane protein FecA.
AB  - The recent structure determination of FecA, with and without ligand, shows the
      existence of two gates. These are the extracellular loops closing over the
      binding site and the plug located inside the barrel. It indicates a process which
      is described as bipartite gating and allows for a rational distinction between
      the binding event and the transport process.

PMID- 12196172
TI  - Investigations of iron uptake in Halobacterium salinarum.
AB  - The iron transport in the extremely halophilic Euryarchaeon Halobacterium
      salinarum JW5 was investigated. Experiments to detect endogenous siderophores
      from H. salinarum failed, but it was able to utilize exogenous siderophores.
      Measurement of the uptake of (55)Fe and [(14)C]citrate gave evidence only for the
      accumulation of iron. Two additional membrane proteins could be detected in iron
      starved cells, one in iron-repleted membranes and one that is up-regulated there.
      Respiratory rates of iron-starved membranes after the addition of succinate and
      NADH differed considerably from iron-repleted ones. Furthermore, both types of
      membrane exhibited different degrees of inhibition by cyanide.

PMID- 12196174
TI  - Mercury transport and resistance.
AB  - Resistance to mercuric ions in bacteria is conferred by mercuric reductase, which
      reduces Hg(II) to Hg(0) in the cytoplasmic compartment. Specific mercuric ion
      transport systems exist to take up Hg(II) salts and deliver them to the active
      site of the reductase. This short review discusses the role of transport proteins
      in resistance and the mechanism of transfer of Hg(II) between the mercury
      resistance proteins.

PMID- 12196173
TI  - Characterization of a non-haem ferritin of the Archaeon Halobacterium salinarum,
      homologous to Dps (starvation-induced DNA-binding protein).
AB  - An iron-rich protein was isolated from the Archaeon Halobacterium salinarum
      sharing a sequence identity of 35% with the starvation-induced DNA-binding
      protein, DpsA, of Synechecoccus sp. PCC 7942. It consists of 20 kDa subunits,
      forming a dodecameric structure. The protein exhibits a ferric iron loading of up
      to 103 Fe ions/mol of holoprotein. CD spectra are consistent with an alpha
      helical contribution of 58%. The UV/visible spectrum provides no evidence for the
      presence of haem groups. This protein exhibits features of a non-haem-type
      bacterial ferritin although it shares only little sequence homology with non-haem
      bacterial ferritin.

PMID- 12196175
TI  - Mercury resistance (mer) operons in enterobacteria.
AB  - Mercury resistance is found in many genera of bacteria. Common amongst
      enterobacteria are transposons related to Tn21, which is both mercuric ion- and
      streptomycin-/spectinomycin- and sulphonamide-resistant. Other Tn21-related
      transposons often have different antibiotic resistances compared with Tn21, but
      share many non-antibiotic-resistance genes with it. In this article we discuss
      possible mechanisms for the evolution of Tn21 and related genetic elements.

PMID- 12196176
TI  - Molecular evidence for the role of a ferric reductase in iron transport.
AB  - Duodenal cytochrome b (Dcytb) is a haem protein similar to the cytochrome b561
      protein family. Dcytb is highly expressed in duodenal brush-border membrane and
      is implicated in dietary iron absorption by reducing dietary ferric iron to the
      ferrous form for transport via Nramp2/DCT1 (divalent-cation transporter 1)/DMT1
      (divalent metal-transporter 1). The protein is expressed in other tissues and may
      account for ferric reductase activity at other sites in the body.

PMID- 12196177
TI  - Relationship between intestinal iron-transporter expression, hepatic hepcidin
      levels and the control of iron absorption.
AB  - Hepcidin is an anti-microbial peptide predicted to be involved in the regulation
      of intestinal iron absorption. We have examined the relationship between the
      expression of hepcidin in the liver and the expression of the iron-transport
      molecules divalent-metal transporter 1, duodenal cytochrome b, hephaestin and
      Ireg1 in the duodenum of rats switched from an iron-replete to an iron-deficient
      diet or treated to induce an acute phase response. In each case, elevated
      hepcidin expression correlated with reduced iron absorption and depressed levels
      of iron-transport molecules. These data are consistent with hepcidin playing a
      role as a negative regulator of intestinal iron absorption.

PMID- 12196178
TI  - Down-regulation of liver iron-regulatory protein 1 in haemochromatosis.
AB  - Cellular iron homoeostasis is maintained by iron sensor proteins known as iron
      regulatory proteins (IRPs), which act post-transcriptionally by binding RNA stem
      loop structures, termed iron-responsive elements (IREs), present on the mRNAs of
      proteins involved in iron storage, utilization and transport. IRP1 is a
      bifunctional protein that can act either as a cytoplasmic aconitase or as an IRE
      binding protein. The RNA-binding activity of IRP1 is regulated post
      translationally by the insertion or extrusion of a 4Fe-4S cluster, without
      changes in the levels of protein. In hereditary haemochromatosis (HH)
      accumulation of iron in parenchymal tissues, including the liver, occurs,
      possibly through dysfunctional IRP1. Investigation of IRP1 expression in liver
      biopsies from HH patients showed that the protein is completely absent or
      markedly reduced in heavily iron-loaded HH patients. Real-time PCR was then
      conducted in an attempt to investigate the mRNA levels and establish the
      underlying mechanism behind the disappearing act of IRP1. The two possibilities
      are: transcriptional regulation (through the inhibition of transcription) or post
      transcriptional regulation (either through increased turnover of protein or
      inhibition of translation) of IRP1. Preliminary data suggest that transcription
      of IRP1 is not affected by chronic iron overload, and down-regulation may be
      attributable instead to degradation of the protein.

PMID- 12196179
TI  - Design and applications of methods for fluorescence detection of iron in
      biological systems.
AB  - Fluorescence metalosensors provide a means to detect iron in biological systems
      that is versatile, economical, sensitive and of a high-throughput nature. They
      rely on relatively high-affinity iron-binding carriers conjugated to highly
      fluorescent probes that undergo quenching after metal complexation. Metal
      specificity is determined by probes containing either an iron-binding moiety of
      high affinity (type A) or of relatively lower affinity (type B) used in
      combination with a strong specific iron chelator. Due to the heterogeneous nature
      of biological systems, the apparent metal-binding affinity and complexation
      stoichiometry ought to be specifically defined. Fluoresceinated moieties coupled
      to metal-binding cores detect Fe at sub-micromolar concentrations and even sub
      microlitre volumes (i.e. cells). Although an ideal probe should also be specific
      for a particular oxidation state of iron, in physiological conditions that
      property might be difficult to attain. Quantification of labile iron in cells has
      relied on the ability of permeant iron chelators to restore the fluorescence of
      probes quenched by intracellular Fe. Modern design of probes aims to (a) improve
      probe targeting to specific cell compartments and (b) create probes that respond
      to metal binding by signal enhancement.

PMID- 12196180
TI  - Plant copper chaperones.
AB  - Copper chaperones, soluble copper-binding proteins, are essential for ensuring
      proper distribution of copper to cellular compartments and to proteins requiring
      copper prosthetic groups. They are found in all eukaryotic organisms. Orthologues
      of the three copper chaperones characterized in yeast, ATX1, CCS and COX17, are
      present in Arabidopsis thaliana. Plants are faced with unique challenges to
      maintain metal homoeostasis, and thus their copper chaperones have evolved by
      diversifying and gaining additional functions. In this paper we present our
      current knowledge of copper chaperones in A. thaliana based on the information
      available from the complete sequence of its genome.

PMID- 12196181
TI  - Iron targeting to mitochondria in erythroid cells.
AB  - Immature erythroid cells have an exceptionally high capacity to synthesize haem
      that is, at least in part, the result of the unique control of iron metabolism in
      these cells. In erythroid cells the vast majority of Fe released from endosomes
      must cross both the outer and the inner mitochondrial membranes to reach
      ferrochelatase, which inserts Fe into protoporphyrin IX. Based on the fact that
      Fe is specifically targeted into erythroid mitochondria, we have proposed that a
      transient mitochondria-endosome interaction is involved in Fe transfer to
      ferrochelatase [Ponka (1997) Blood 89, 1-25]. In this study, we examined whether
      the inhibition of endosome mobility within erythroid cells would decrease the
      rate of (59)Fe incorporation into haem. We found that, in reticulocytes, the
      myosin light-chain kinase inhibitor, wortmannin, and the calmodulin antagonist, W
      7, caused significant inhibition of (59)Fe incorporation from (59)Fe-transferrin
      labelled endosomes into haem. These results, together with confocal microscopy
      studies using transferrin and mitochondria labelled by distinct fluorescent
      markers, suggest that, in erythroid cells, endosome mobility, and perhaps their
      contact with mitochondria, plays an important role in a highly efficient
      utilization of iron for haem synthesis.

PMID- 12196182
TI  - The Wilson's disease protein expressed in Sf9 cells is phosphorylated.
AB  - The Wilson's disease protein (WNDP), a copper transporter, is a crucial mediator
      of copper homoeostasis in mammalian cells. We recently found that changes in
      copper concentration regulate the phosphorylation level of WNDP. WNDP
      phosphorylation was observed in several mammalian cell lines, suggesting that a
      common phosphorylation pathway exists in these cells. Here we demonstrate that
      WNDP expressed in Sf9 insect cells is also phosphorylated, as evidenced by
      metabolic labelling of these cells with [(32)P]P(i). Because the baculovirus
      system allows us to generate large amounts of protein, we are using this
      expression method to isolate WNDP and map the sites of WNDP phosphorylation. The
      identification of phosphorylation sites is the first step towards understanding
      the physiological role of WNDP phosphorylation.

PMID- 12196185
TI  - Chromium(VI)-induced damage to the cytoskeleton and cell death in isolated
      hepatocytes.
AB  - Cr(VI) is a known human carcinogen. Although it has been investigated widely, the
      mechanism(s) of its action is/are not fully understood. The aim of this study was
      to evaluate Cr(VI)-induced damage to the cell cytoskeleton and the mode of cell
      death in primary cultures of hepatocytes. Exposure of the cultured cells
      (10(5)/cm(2)) to 1 and 5 microM Cr(VI) for 24 h resulted in loss of the cell
      cytoskeleton, and this was accompanied by membrane blebbing and shrinking of the
      cell. Staining of the cells with annexin V and propidium iodide showed that
      Cr(VI) induces apoptosis at low concentrations (5 microM), whereas at higher
      concentrations (25 microM) it induces necrosis. This study shows that Cr(VI)
      causes damage to the cell cytoskeleton, and induces apoptosis at low
      concentrations. However, the importance of necrosis and apoptosis in vivo, and
      the effects of longer exposure times, which simulate environmental and
      occupational exposure to Cr(VI), remain to be investigated.

PMID- 12196183
TI  - Copper and prion diseases.
AB  - Transmissible spongiform encephalopathies are diseases of animals and humans that
      are also termed prion diseases. These diseases are linked together because a
      normal brain glycoprotein termed the prion protein is converted to a readily
      detectable protease-resistant isoform. There is now strong evidence to suggest
      that apart from this difference in resistance a major difference between the
      isoforms is that the normal prion protein binds copper and has an anti-oxidant
      function. Brains from Creutzfeldt-Jakob disease patients and brains from mice
      with experimental mouse scrapie have been shown to have changes in the levels of
      both copper and manganese. There is growing evidence that links prion diseases to
      disturbances of metal metabolism.

PMID- 12196186
TI  - Design of therapeutic chelating agents.
AB  - The successful design of orally active non-toxic selective metal chelators is a
      much sought-after goal. In order to identify an ideal chelator for clinical use,
      a range of specifications must be considered, such as metal selectivity and
      affinity, kinetic stability of the complex, bioavailability and toxicity. In this
      overview the comparative properties of ligands capable of endowing complexes with
      such properties will be discussed.

PMID- 12196184
TI  - Toxicity of myoglobin and haemoglobin: oxidative stress in patients with
      rhabdomyolysis and subarachnoid haemorrhage.
AB  - Haemolytic events, such as those following rhabdomyolysis and subarachnoid
      haemorrhage, often result in pathological complications such as vasoconstriction.
      Haem-protein cross-linked myoglobin and haemoglobin are generated by ferric
      ferryl redox cycling, and thus can be used as markers of oxidative stress. We
      have found haem-protein cross-linked myoglobin in the urine of patients suffering
      from rhabdomyolysis and haem-protein cross-linked haemoglobin in the
      cerebrospinal fluid of patients following subarachnoid haemorrhage. These
      findings provide strong evidence that these respiratory haem proteins can be
      involved in powerful oxidation processes in vivo. We have previously proposed
      that these oxidation processes in rhabdomyolysis include the formation of potent
      vasoconstrictor molecules, generated by the myoglobin-catalysed oxidation of
      membranes, inducing nephrotoxicity and renal failure. Haem-protein cross-linked
      haemoglobin in cerebrospinal fluid suggests that a similar mechanism of lipid
      oxidation is present and that this may provide a mechanistic basis for the
      delayed vasospasm that follows subarachnoid haemorrhage.

PMID- 12196187
TI  - The role of oxidative stress in the toxicity of pyridoxal isonicotinoyl hydrazone
      (PIH) analogues.
AB  - Pyridoxal isonicotinoyl hydrazone (PIH) analogues are effective iron chelators in
      vivo and in vitro, and may be of value for the treatment of secondary iron
      overload. The sensitivity of Jurkat cells to Fe-chelator complexes was enhanced
      several-fold by the depletion of the antioxidant glutathione, indicating the role
      of oxidative stress in their toxicity. K562 cells loaded with eicosapentaenoic
      acid, a fatty acid particularly susceptible to oxidation, were also more
      sensitive to the toxic effects of the Fe complexes, and toxicity was proportional
      to lipid peroxidation. Thus Fe-chelator complexes cause oxidative stress, which
      may be a major component of their toxicity. As was the case for their Fe
      complexes, the toxicity of PIH analogues was enhanced by glutathione depletion of
      Jurkat cells and eicosapentaenoic acid-loading of K562 cells. Thus the toxicity
      of the chelators themselves is also enhanced by compromised cellular redox
      status. In addition, the toxicity of the chelators was diminished by culturing
      Jurkat cells under hypoxic conditions, which may limit the production of the
      reactive oxygen species that initiate oxidative stress. A significant part of the
      toxicity of the chelators may be due to intracellular formation of Fe-chelator
      complexes, which oxidatively destroy the cell.

PMID- 12196188
TI  - Novel cytotoxic chelators that bind iron(II) selectively over zinc(II) under
      aqueous aerobic conditions.
AB  - To achieve cellular iron deprivation by chelation, it is important to develop
      chelators with selective metal-binding properties. Selectivity for iron has long
      been the province of certain oxygen-donor chelators such as desferrioxamine,
      which target Fe(III) and exploit the strength of a relatively ionic Fe(III)-O
      interaction. We have been studying novel chelators that possess mechanisms to
      selectively chelate +2 biometals, particularly tachpyr [N,N',N"-tris(2
      pyridylmethyl)-1,3,5-cis,cis-triaminocyclohexane] and derivatives from N,N',N"
      trialkylation and pyridine ring alkylation. Metal-exchange and metal-binding
      competition reactions have been conducted at pH 7.4, 37 degrees C and time
      periods until no further change was observed (generally 24-48 h). Under anaerobic
      conditions, tachpyr is strongly selective for iron, binding 95+/-5% Fe(II) versus
      5+/-5% Zn(II) in the forms [Fe(tachpyr)](2+) and [Zn(tachpyr)](2+) respectively.
      Under aerobic conditions, tachpyr complexes Fe(II) more effectively than Fe(III),
      forming iminopyridyl complexes [Fe(tachpyr-ox-n)](2+) (n=2, 4) by O(2)-induced
      and iron-mediated oxidative dehydrogenation. Complexes [Fe(tachpyr-ox-n)](2+) are
      also strongly bound forms of iron that are unaffected by an excess of Zn(II) (75
      mol zinc:1 mol iron complex). The preference of tachpyr for iron over zinc under
      aerobic conditions appears to be hindered by oxidation of Fe(II) to Fe(III), such
      that the proportions bound are 44+/-10% Fe(II) versus 56+/-10% Zn(II), in the
      respective forms [Fe(tachpyr-ox-n)](2+) and [Zn(tachpyr)](2+). However, upon
      addition of the reducing agent Na(2)S(2)O(4) that converts Fe(III) to Fe(II), the
      binding proportions shift to 76+/-10% Fe(II) versus 24+/-10% Zn(II),
      demonstrating a clear preference of tachpyr for Fe(II) over Zn(II). Iron(II) is
      in the low-spin state in [Fe(tachpyr)](2+) and [Fe(tachpyr-ox-n)](2+) (n=2, 4),
      which is a likely cause of the observed selectivity. N-methylation of tachpyr
      [giving (N-methyl)(3)tachpyr] results in the loss of selectivity for Fe(II),
      which is attributed to the steric effect of the methyl groups and a resulting
      high-spin state of Fe(II) in [Fe(N-methyl)(3)tachpyr)](2+). The relationship of
      chelator selectivity to cytotoxicity in the tach family will be discussed.

PMID- 12196189
TI  - The influence of iron homoeostasis on macrophage function.
AB  - Iron loading of alveolar macrophages in vivo significantly altered their ability
      to respond to various inflammatory stimuli. This was exemplified by reduced
      synthesis of inducible nitric oxide synthase after stimulus with
      lipopolysaccharide and interferon gamma, and an enhanced activation of nuclear
      factor kappa B in the absence of tumour necrosis factor alpha stimulation, and
      enhanced production of reactive oxygen species after activation with activated
      zymosan and PMA. Such results may indicate an imbalance in the production of
      reactive oxygen and reactive nitrogen species generated by the iron-loaded
      macrophages after an appropriate stimulus.

PMID- 12196190
TI  - Responses of plants to iron, zinc and copper deficiencies.
AB  - Iron, copper and zinc are essential metals for cell metabolism. Plants have
      evolved different schemes to efficiently mobilize low-solubility nutrients such
      as metals from their environment and to transport them between organs. In this
      review we highlight the divergences and convergences of the iron, copper and zinc
      uptake, transport and homoeostatic pathways.

PMID- 12196192
TI  - Structural studies of the Fur protein from Rhizobium leguminosarum.
AB  - The X-ray crystal structure of the apo-form of the Fur protein from Rhizobium
      leguminosarum has been solved at 2.7 A resolution. Small-angle X-ray scattering
      was used to give information on the solution conformation of the protein. The Fur
      homodimer folds into two domains. The N-terminal domain is formed from the
      packing of two helix-turn-helix motifs while the C-terminal domain appears
      primarily to stabilize the dimeric state of the protein.

PMID- 12196191
TI  - Manganese transport and its regulation in bacteria.
AB  - Regulation of manganese acquisition by bacteria occurs by both biochemical
      regulation of the activity of the transporters and transcriptional regulation of
      gene expression. Structural analysis suggests that calcium ions may regulate the
      function of an Mn ATP-binding cassette (ABC)-permease in Synechocystis 6803, a
      cyanobacterium, as well as in a number of other bacteria. The expression of genes
      encoding the manganese transporter in Synechocystis 6803 is regulated by a two
      component signal-transduction mechanism that has not been previously observed for
      manganese and zinc transport in bacteria.

PMID- 12196193
TI  - c-Myc represses the murine Nramp1 promoter.
AB  - The Nramp1 (natural resistance-associated macrophage protein 1) gene modulates
      the growth of intracellular pathogens and encodes a divalent cation transporter
      within lysosomes/late endosomes of macrophages. Nramp1 modulates the cytoplasmic
      iron pool. Wu, Polack and Dalla-Favera [(1999) Science 283, 676-679] showed
      reciprocal control of H-ferritin and IRP2 by c-Myc, and suggest that c-Myc
      regulates genes to increase cytoplasmic iron. A role for c-Myc in Nramp1
      regulation was evaluated. Co-transfection studies show that c-Myc represses
      Nramp1 promoter function. Five non-canonical Myc-max binding sites (E-box)
      identified within the Nramp1 5'-flanking sequence are not responsible for the
      inhibitory effects of c-Myc on Nramp1 expression. An initiator(s) adjacent to the
      transcription-initiation site is a candidate for the inhibition observed. Results
      are consistent with a role for Nramp1 removing iron from the cytosol and
      antagonizing c-Myc function.

PMID- 12196194
TI  - Repression of ferritin expression modulates cell responsiveness to H-ras-induced
      growth.
AB  - We assessed the role of the cell labile iron pool in mediating oncogene-induced
      cell proliferation via repression of ferritin expression. When HEK-293 cells,
      engineered to inducibly express either active (+) or dominant-negative (-) forms
      of the H-ras oncogene, were treated with antisense nucleotides to ferritin
      subunits they displayed (a) decreased ferritin levels, (b) increased labile iron
      pool and either (c) faster growth in cells induced to express H-Ras (+) or (d)
      recovery from growth retardation in dominant-negative H-Ras-induced cells. Our
      studies support the view that the role of down-modulation of ferritin expression
      by some oncogene-evoked proliferation proceeds via expansion of the cellular
      labile iron pool.

PMID- 12196195
TI  - Identification of members of the Aspergillus nidulans SREA regulon: genes
      involved in siderophore biosynthesis and utilization.
AB  - Iron is an essential trace element for almost all organisms. However, an excess
      of this metal within cells can be deleterious on account of catalysis of cell
      damaging hydroxyl radicals. Therefore, the concentration of iron within cells is
      tightly regulated and the primary control occurs by regulating its uptake. Under
      conditions of low iron availability, most fungi mobilize extracellular iron by
      excretion of low-molecular-mass ferric iron chelators, termed siderophores. Due
      to the potential impact of iron metabolism on fungal pathogenicity, a better
      insight into siderophore-mediated iron uptake is needed. In Aspergillus nidulans,
      siderophore biosynthesis and uptake are negatively regulated by the GATA-type
      transcription factor SREA. Hence, genes involved in siderophore biosynthesis and
      uptake are characterized by transcriptional induction under iron limitation in
      wild-type strain and de-repression in an sreA-deletion strain under conditions of
      sufficient iron supply. Such genes have been searched for using different
      strategies, e.g. differential mRNA display and expression analysis of candidate
      genes from various A. nidulans sequence databases. The identified genes
      presumably encode enzymes needed for siderophore biosynthesis, and transporters
      involved in siderophore uptake and/or excretion. The functional characterization
      of these genes will help to unravel the pathways involved in siderophore
      biosynthesis and uptake.

PMID- 12196197
TI  - A flexible technology platform to explore valuable drug targets.
AB  - The high-throughput screening platform implemented for drug discovery is driven
      by the therapeutic areas of interest. Therefore the speed and information derived
      is governed by these areas. Multiple technologies are needed to exploit this and
      it is also important to show reactivity to new advances in technology. In
      contrast with a drive over the last few years towards higher throughput and
      speed, higher information content will be instrumental in driving lead discovery
      in the future.

PMID- 12196198
TI  - Strategies to identify ligands for orphan G-protein-coupled receptors.
AB  - G-protein-coupled receptors are the most tractable class of protein targets for
      small molecule drug design. Sequencing of the human genome allied to bio
      informatic analysis has identified a large number of putative receptors for which
      the natural ligands remain undefined. A range of currently employed and
      developing strategies to identify ligands that interact with these orphan
      receptors and to validate them as drug targets are described and discussed.

PMID- 12196199
TI  - High-throughput screening in the diagnostics industry.
AB  - The diagnostics industry is constantly under pressure to bring innovation quicker
      to market and so the impetus to speed up product-development cycle times becomes
      greater. There are a number of steps in the product-development cycle where the
      application of high-throughput screening can help. In the case of lateral-flow
      immuno-diagnostics the selection of antibody reagents is paramount. In
      particular, rapid identification of antibody pairs that are able to 'sandwich'
      around the target antigen is required. One screen that has been applied
      successfully is the use of surface plasmon resonance biosensors like Biacore.
      Using such a system one can evaluate over 400 antibody pairings in under 5 days.
      Conventional approaches to screen this number of antibody pairs would take many
      months. Other automated screening systems like DELFIA can be used in processing
      the vast amount of tests required for clinical trials. In addition, the use of
      robotics to automate routine product testing can be used to shorten the product
      development cycle.

PMID- 12196200
TI  - Virtual screening: a real screening complement to high-throughput screening.
AB  - Virtual screening is being routinely used as an integral part of today's hit
      identification strategies for, on one hand, prioritizing large corporate
      screening collections and, on the other hand, to extend the scope of screening to
      external databases. A brief description of the essential elements required for
      virtual screening and an application example to the identification of agonist
      hits for the oestrogen receptor subtype ER alpha are presented.

PMID- 12196201
TI  - Conditionally immortalized cell lines as model systems for high-throughput
      biology in drug discovery.
AB  - There is an increasing emphasis on the need for high-quality biological data much
      earlier in the drug-discovery process. This has led to the development of high
      throughput approaches to biology, many of which rely on the use of cell-culture
      models. Unfortunately, available cell-culture models often reflect poorly the
      characteristics of the tissue they are supposed to represent. However, the
      conditional-immortalization approach as applied by Xcellsyz offers the
      possibility of producing human cell lines on demand, which are truly
      representative of the tissue from which they derive.

PMID- 12196202
TI  - Miniaturized screening technologies for drug discovery.
AB  - Adaptive Profiling (APL) and other biochip companies aim to harness the power of
      microsystems technology together with advances in chemistry and molecular
      biology, to become service and technology providers to organizations involved in
      pharmaceutical research and development. By supplying a unique range of decision
      making tools that aid an earlier identification of qualified drug candidates for
      clinical development, the company should gain a significant share of the 10
      billion US dollar biological screening, bioavailability and toxicity assessment
      market.

PMID- 12196203
TI  - CD19-CD21 complex regulates an intrinsic Src family kinase amplification loop
      that links innate immunity with B-lymphocyte intracellular calcium responses.
AB  - CD19 is a B-lymphocyte cell surface molecule that functions as a general response
      regulator or rheostat, which defines intrinsic and B-cell antigen receptor
      induced signalling thresholds that are critical for humoral immunity and
      expansion of the peripheral B-cell pool. In addition, B-cell responses are
      influenced by signals transduced through a CD19-CD21 cell surface receptor
      complex, where the binding of complement C3d to CD21 links humoral immune
      responses with the innate immune system. This review outlines recent biochemical
      and genetic studies that characterize the signal transduction pathways utilized
      by this receptor complex to regulate B-cell intracellular calcium responses.

PMID- 12196204
TI  - B-cell development and antigen receptor signalling.
AB  - B-cell development and function requires the products of the Vav family of genes.
      Vav proteins act as key components of the antigen receptor signal transduction
      machinery by integration of signals that control the cell cycle, differentiation
      and apoptosis. At the molecular level, Vav proteins regulate small-molecular-mass
      GTPases, phosphoinositide 3-kinase, TEC family tyrosine kinases and intracellular
      calcium flux.

PMID- 12196205
TI  - Hyper-IgM syndromes: a model for studying the regulation of class switch
      recombination and somatic hypermutation generation.
AB  - Several genetic defects in class switch recombination, which lead to a hyper-IgM
      syndrome, have been described recently in humans. In addition to the well known
      role of CD40-ligand-CD40 interaction, these pathologies demonstrate definitively
      the requirement of CD40-mediated nuclear factor kappa B activation and the
      essential role of a recently described molecule, the activation-induced cytidine
      deaminase in an efficient humoral response, which includes class switch
      recombination and the production of high-affinity antibodies.

PMID- 12196206
TI  - Consequences of Fc gamma receptor type III reactivity in non-organ-specific
      autoimmune diseases.
AB  - Polymorphonuclear neutrophils (PMNs) express constitutively the Fc gamma
      receptors (Fc gamma Rs) Fc gamma RIIIb and Fc gamma RIIa for the Fc part of IgG,
      and soluble Fc gamma RIIIb (sFc gamma RIIIb) has been identified. Elevated levels
      of sFc gamma RIIIb were detected in non-organ-specific autoimmune conditions, and
      there was a considerably decreased number of PMNs undergoing apoptosis in the
      presence of sFc gamma RIIIb. Anti-Fc gamma RIIIb autoantibodies (autoAbs) have
      also been described in such patients. They are not cytotoxic to these cells, but
      they extend their survival. The anti-apoptotic signal can be transduced through
      Fc gamma RIIa and/or CD11b, the beta-chain of the complement receptor 3. However,
      Fc gamma RIIIb appears to be also competent. Anti-Fc gamma RIIIb-conditioned
      supernatant from cultured PMNs induces the transcription of messenger RNA for
      granulocyte colony-stimulating factor and granulocyte/macrophage colony
      stimulating factor, followed by protein synthesis. The delay in apoptosis may be
      generated by a downregulation of the death promoter Bax. Inflammation might thus
      be modulated by sFc gamma RIIIb and anti-Fc gamma RIIIb autoAbs in systemic
      diseases.

PMID- 12196207
TI  - B-lymphocyte depletion therapy in rheumatoid arthritis and other autoimmune
      disorders.
AB  - B-lymphocyte depletion therapy is being explored in a wide range of autoimmune
      disorders. In many, there is early evidence for efficacy, and immunosuppression
      has not been a major problem. The mechanism of action is unclear, but appears to
      be consistent with the lowering of autoantibody levels, where relevant antibodies
      are quantifiable. An interesting finding is the persistence of clinical
      improvement for periods of 1 year or more after B-lymphocyte return, which
      supports the concept that stochastic generation of rare pathogenic B-lymphocyte
      subsets may be a rate-limiting step in pathogenesis.

PMID- 12196208
TI  - COUP-TF (chicken ovalbumin upstream promoter transcription factor)-interacting
      protein 1 (CTIP1) is a sequence-specific DNA binding protein.
AB  - Chicken ovalbumin upstream promoter transcription factor (COUP-TF)-interacting
      proteins 1 and 2 [CTIP1/Evi9/B cell leukaemia (Bcl) l1a and CTIP2/Bcl11b
      respectively] are highly related C(2)H(2) zinc finger proteins that are
      abundantly expressed in brain and the immune system, and are associated with
      immune system malignancies. A selection procedure was employed to isolate high
      affinity DNA binding sites for CTIP1. The core binding site on DNA identified in
      these studies, 5'-GGCCGG-3' (upper strand), is highly related to the canonical GC
      box and was bound by a CTIP1 oligomeric complex(es) in vitro. Furthermore, both
      CTIP1 and CTIP2 repressed transcription of a reporter gene harbouring a
      multimerized CTIP binding site, and this repression was neither reversed by
      trichostatin A (an inhibitor of known class I and II histone deacetylases) nor
      stimulated by co-transfection of a COUP-TF family member. These results
      demonstrate that CTIP1 is a sequence-specific DNA binding protein and a bona fide
      transcriptional repressor that is capable of functioning independently of COUP-TF
      family members. These findings may be relevant to the physiological and/or
      pathological action(s) of CTIPs in cells that do not express COUP-TF family
      members, such as cells of the haematopoietic and immune systems.

PMID- 12196212
TI  - Recent approaches in acute lymphoblastic leukemia in adults.
AB  - In the last decades outcome of adult acute lymphoblastic leukemia (ALL) has
      improved considerably. In large multicenter studies remission rates range from
      75% to 89%, and long-term leukemia-free survival (LFS) from 28% to 39%. Major
      progress has also been made regarding better characterization of subtypes of ALL.
      Complete diagnostic procedures are essential to identify these subtypes which
      have significant differences in clinical and laboratory features and prognosis.
      LFS of > 50% can be expected in favorable subtypes such as T-ALL or mature B-ALL,
      while LFS of < 20% is expected in Ph/BCR-ABL positive ALL. Prognostic factors can
      be used for risk stratification and selection of treatment strategies can be
      adapted to the subtype and relapse risk. This includes measurement of minimal
      residual disease (MRD) to evaluate individualized treatment strategies adapted to
      the molecular response. Several new approaches for improvement in chemotherapy
      and stem cell transplantation (SCT) are under investigation. They include the use
      of intensified anthracyclines, asparaginase, cyclophosphamide or high-dose
      cytarabine during induction and intensive rotational chemotherapy during
      consolidation. Also SCT - mainly from sibling donors - is now part of standard
      treatment of de novo ALL, although it remains open whether indications should be
      based on prognostic factors or whether SCT should be offered to all patients with
      sibling donor. However, substantial progress can only be achieved by new,
      experimental strategies. These include new approaches for SCT, such as
      nonmyeloablative SCT, measurement of MRD, causal treatment with molecular
      targeting, e.g. with kinase inhibitors, and antibody therapy.

PMID- 12196211
TI  - Cytogenetics and molecular genetics of acute lymphoblastic leukemia.
AB  - An important factor in the diagnosis of acute lymphoblastic leukemia (ALL) is
      that karyotype is an independent prognostic indicator, with an impact on the
      choice of treatment. Outcome is related to the number of chromosomes. For
      example, high hyperdiploidy (51-65 chromosomes) is associated with a good
      prognosis, whereas patients with near haploidy (23-29 chromosomes) have a poor
      outcome. The discovery of recurring chromosomal abnormalities in the leukemic
      blasts of patients with ALL has identified a large number of genes involved in
      leukemogenesis. Certain specific genetic changes are related to prognosis. The
      ETV6/AML1 fusion arising from the translocation (t12;21) (p13;q22) has been
      associated with a good outcome; the BCR/ABL fusion of (t9;22)(q34;q11),
      rearrangements of the MLL gene, and abnormalities of the short arm of chromosomes
      9 involving the tumor suppressor genes p16INK4A have a poor prognosis.
      Unfortunately, the classification of patients into prognostic groups based on
      cytogenetics is not always as predicted. Even when other clinically based risk
      factors are taken into account, some patients with good-risk cytogenetic features
      will relapse. In the search for new measures of prognosis, it has recently
      emerged that the level of minimal residual disease following induction therapy
      can be a reliable predictor of outcome in ALL.

PMID- 12196209
TI  - Molecular cloning, expression and characterization of a novel class glutathione S
      transferase from the fungus Cunninghamella elegans.
AB  - The structural gene for glutathione S-transferase (CeGST1-1) in the fungus
      Cunninghamella elegans was cloned by screening a cDNA library using a degenerate
      oligonucleotide probe based on the N-terminal sequence of the purified protein.
      Open reading frame analysis indicated that the cegst1 gene encodes a protein of
      210 amino acid residues. The deduced amino acid sequence showed 25% sequence
      identity with the sequence of the Pi-class GST from Danio rerio (zebrafish).
      Similarity was also shown with the Alpha-class GST from Fasciola hepatica (liver
      fluke; 23% identity), the Mu class from Mus musculus (22%) and the Sigma class
      from Ommastrephes sloani (squid; 21%). Further screening of a cDNA library with
      the cegst1 gene probe revealed the presence of another GST isoenzyme (CeGST2-2)
      in this fungus, which shows 84% sequence identity with CeGST1-1 at the amino acid
      level. Reverse transcription PCR revealed that cegst2 was also expressed at the
      mRNA level in the fungus C. elegans. Both cegst genes were overexpressed in
      Escherichia coli using the expression vector pQE51, displaying specific
      activities with 1-chloro-2,4-dinitrobenzene of 2.04 and 0.75 micromol/min per mg
      of protein respectively. Both enzymes exhibited a similar substrate specificity
      and inhibition profile, indicating that CeGST1-1 and CeGST2-2 belong to the same
      GST class. Mutagenesis analysis revealed that Tyr(10) in the N-terminal region is
      essential for catalysis of CeGST1-1. We propose from these results that the
      CeGSTs are novel Gamma-class GSTs and designated as GSTG1-1 and GSTG2-2
      respectively.

PMID- 12196213
TI  - Philadelphia chromosome-positive acute lymphoblastic leukemia- current concepts
      and future perspectives.
AB  - Philadelphia chromosome (Ph)-positive acute lymphoblastic leukemia (ALL) is
      diagnosed rarely in children, but constitutes the most frequent cytogenetic
      abnormality in adults with ALL. In contrast to chronic myeloid leukemia (CML),
      patients with Ph-positive ALL usually demonstrate expression of a truncated
      version of the BCR-ABL protein called p190bcr-abl. Irrespective of age and
      breakpoint location, Ph-positive ALL carries a poor prognosis. Although remission
      rates are identical to those of Ph-negative ALL, relapse is almost universal and
      long-term survival remains rare. Given the poor outcome with current chemotherapy
      consolidation programs, stem cell transplantation is usually recommended for
      these patients in first remission or as soon as feasible. Even with
      transplantation the impact on outcome is limited and new therapeutic concepts are
      urgently needed. One of the most promising developments in recent years has been
      the introduction of the tyrosine kinase inhibitors such as STI571. An overview of
      current treatment modalities in Ph-positive ALL will be provided and the
      rationale for new therapies will be discussed.

PMID- 12196214
TI  - Childhood acute lymphoblastic leukemia.
AB  - As cure rates in childhood acute lymphoblastic leukemia reach 80%, emphasis is
      increasingly placed on the accurate identification of drug-resistant cases, the
      elucidation of the mechanisms involved in drug resistance and the development of
      new therapeutic strategies targeted toward the pivotal molecular lesions.
      Pharmacodynamic and pharmacogenomic studies have provided rational criteria for
      individualizing therapy to enhance efficacy and reduce acute toxicity and late
      sequelae. Currently, assessment of the early response to treatment by measurement
      of minimal residual disease (MRD) is the most powerful independent prognostic
      indicator. MRD is affected by both the drug sensitivity of leukemic cells and the
      pharmacodynamic and pharmacogenetic properties of the host cells. Rapid advances
      in biotechnology and bioinformatics should ultimately facilitate the development
      of molecular diagnostic assays that can be used to optimize antileukemic therapy
      and elucidate the mechanisms of leukemogenesis. In the interim, prospective
      clinical trials have provided valuable clues that are further increasing the cure
      rate of childhood acute lymphoblastic leukemia.

PMID- 12196215
TI  - Towards an integrated classification of adult acute lymphoblastic leukemia.
AB  - Acute lymphoblastic leukemia (ALL) represents a biologically and clinically
      heterogeneous group of diseases characterized by the abnormal proliferation and
      accumulation of immature lymphoid cells within the bone marrow and lymphoid
      tissues. Following a diagnostic work-up, prognostic data are routinely achieved
      through physical examination, serum biochemical profiles, peripheral blood count
      and bone marrow morphology. Over the years, information obtained through
      karyotype, molecular genetics, extensive immunophenotype, multidrug resistance
      and, more recently, genomic profiling is progressively contributing to a better
      understanding of the biology of this complex disease, to the identification of
      subgroups of patients with a different clinical outcome, to the more precise
      monitoring of minimal residual disease, to the use of different therapeutic
      protocols based on prognostic indicators and, recently, also to the design of
      innovative and specific treatment strategies. In the present review, we will
      discuss how an integrated approach is now mandatory for the optimal management of
      adult ALL.

PMID- 12196217
TI  - Efficiency of the 0.04 taper ProFile during the re-treatment of gutta-percha
      filled root canals.
AB  - AIM: The objective of this study was to determine the effectiveness of 0.04
      ProFile instruments during the removal of root fillings. METHODOLOGY: A total of
      30 single-rooted mandibular canines were divided into three groups. The canals
      were accessed and then prepared with a reciprocating automated device and nickel
      titanium files. Three different techniques of obturation were used: Thermafil
      system (group I), thermomechanical compaction (group II) and lateral condensation
      (group III). Sealer 26 was used in all three groups. Two weeks after obturation,
      the fillings were removed using 0.04 ProFile instruments following standardized
      sequence of size 90, 60, 45, 40, 35 and 30 at a speed of 300 rpm in a crown-down
      manner. The teeth were subsequently split with a chisel, photographs were taken
      with a colour video camera and the removal of filling material was assessed
      visually (by colour) by two examiners. The time required to achieve the working
      length was also recorded. RESULTS: ProFile instruments reached the working length
      in all cases. However, complete removal of gutta-percha occurred in only three
      specimens (two of group I, and one of group II). Thermafil plastic carriers were
      removed successfully in all specimens of group I. CONCLUSIONS: ProFile
      instruments with 0.04 taper were inadequate in completely removing the filling
      materials from the root canal system. However, the ideal working length was
      achieved rapidly.

PMID- 12196218
TI  - Corrosion rates of stainless-steel files in different irrigating solutions.
AB  - AIM: The present study was designed to evaluate and compare the corrosion rates
      of the stainless-steel endodontic files when immersed in 0.2% chlorhexidine
      gluconate, 5.25% NaOCl, chlorinated soda with KOH, and 17% EDTA irrigating
      solutions. METHODOLOGY: Corrosion rates of stainless-steel K-files in irrigating
      solutions were determined electrochemically by the Tafel extrapolation method.
      The cutting flutes of files were immersed in solutions and used as an electrode.
      A saturated calomel electrode (SCE) was used as a reference, and a platinum plate
      was used as a counter electrode. In order to determine corrosion rates, the
      linear part of anodic currents obtained from electrochemical current-potential
      curves, was extrapolated to corrosion potentials. RESULTS: The corrosion rates of
      stainless-steel files in the tested solutions from the highest to the lowest
      were: 0.2% chlorhexidine gluconate>5.25% NaOCl>chlorinated soda with KOH>17%
      EDTA. The differences between the corrosion rates of files were not found to be
      statistically different for chlorinated soda with KOH and EDTA (P >0.05), but
      statistically significant differences were found amongst other groups.
      CONCLUSIONS: The results of the present study indicated that 0.2% chlorhexidine
      gluconate, 5.25% NaOCl and chlorinated soda with KOH cause severe corrosion on
      the surface of selected stainless-steel files.

PMID- 12196219
TI  - Periapical healing of endodontically treated teeth in one and two visits
      obturated in the presence or absence of detectable microorganisms.
AB  - AIM: The purpose of the present study is to evaluate the healing of periapical
      lesions of teeth with positive and negative canal cultures at the time of
      obturation, and to evaluate the periapical healing of teeth treated in one visit
      (without) or in two visits with an interappointment dressing of calcium
      hydroxide. METHODOLOGY: Thirty-nine patients received root-canal treatment. In
      the first visit, teeth were instrumented, and 18 of these teeth were filled
      (after microbiological sampling) with calcium hydroxide in sterile saline. The
      other 21 teeth were obturated with gutta-percha and AH-26 sealer after
      microbiological sampling. Four weeks later, the teeth with calcium hydroxide were
      accessed again and after microbiological sampling they were obturated with gutta
      percha and AH-26 sealer. Healing of periapical radiolucency was recorded over a
      period up to 4.5 years. RESULTS: In both the treatment groups, the size of the
      periapical lesions reduced significantly during the follow-up period. Complete
      radiographic healing was observed in 81% of the cases in the one-visit group, and
      in 71% of the cases in the two-visit group. The probability of success increased
      continuously over time for both treatment groups. Seven out of eight cases
      (87.5%) that showed a positive root-canal culture at the time of obturation
      healed. The number of colony forming units (CFU) in six out of eight positive
      canals was <10(2) CFU mL(-1). CONCLUSIONS: Within the limitations of this study,
      no significant differences in healing of periapical radiolucency was observed
      between teeth that were treated in one visit (without) and two visits with
      inclusion of calcium hydroxide for 4 weeks. The presence of a positive bacterial
      culture (CFU<10(2)) at the time of filling did not influence the outcome of
      treatment.

PMID- 12196220
TI  - Comparative in-vitro evaluation of three chelator pastes.
AB  - AIM: To compare the effect of three paste chelating agents on the root dentine of
      extracted teeth: Calcinase-Slide (lege artis, Dettenhausen, Germany), Glyde-File
      (DeTrey/Dentsply, Konstanz, Germany), RC-Prep (Premier, Norristown, USA).
      METHODOLOGY: Ten slices of root dentine were covered with one of the chelating
      agents for 30 s, 1 min and 2 min and irrigated with 5 mL H2O2 and NaOCl. This was
      repeated five times. Pre- and postoperative Vickers hardness of root dentine was
      measured. Twenty slices of root dentine were covered with 0.1 mL of the chelating
      agents for 3, 6 and 9 min. Differences between pre- and postoperative weight were
      recorded. Ten root canals of extracted teeth were enlarged five ISO-sizes with
      0.1 mL chelator paste for each file. The teeth were split longitudinally and
      cleanliness of the root-canal walls was evaluated under the SEM using a four
      score evaluation index. Results were statistically analysed using the Wilcoxon
      Mann-Whitney test, the Friedman test and the Kruskal-Wallis test with P<0.05 for
      all tests. RESULTS: No significant differences between the chelating agents were
      found in terms of changes in dentine hardness. Loss of hardness increased
      significantly with increasing time of contact of the chelating pastes with
      dentine. There were significant differences between the three chelating agents
      and the control for loss of weight. After 3 min there was no significant
      difference between the chelating agents, after 6 and 9 min Calcinase-Slide showed
      significantly more weight loss than RC-Prep; after 6 min Glyde-File showed
      significantly more weight loss than RC-Prep. In the coronal and middle parts of
      the root canals, the cleaning ability of Calcinase-Slide was significantly better
      than of RC-Prep and Glyde-File; in the apical third no differences could be
      found. CONCLUSIONS: Under the circumstances of this in vitro study, the three
      chelator pastes evaluated had no or only slight differences in terms of weight
      loss, changes of Vickers hardness in root dentine and cleanliness of root-canal
      walls. The use of a chelating agent may be useful to enhance cleanliness of the
      coronal and middle part of the root canal.

PMID- 12196221
TI  - Periapical health related to the quality of coronal restorations and root
      fillings.
AB  - AIMS: To evaluate the impact of the quality of coronal restorations scored on a
      clinical and radiographic basis and the quality of root fillings on periapical
      health. METHODOLOGY: Periapical radiographs were taken of 745 root-filled teeth,
      randomly selected from patients attending the Ghent University Dental School. The
      teeth had not received restorative treatment in the previous year. The coronal
      status was scored both clinically according to modified Ryge's criteria, and
      radiographically by evaluating the presence of signs of marginal leakage or
      decay. The quality of the root filling was scored according to criteria of length
      and homogeneity and the periapical status was categorized on the basis of
      presence or absence of radiographic signs of apical periodontitis. The
      relationship between coronal status, quality of root filling and periapical
      health was determined. The data were analyzed using Chi2 test, Odds ratio,
      Spearman's r(S) and logistic regression. RESULTS: Thirty-three percent of the
      teeth had apical periodontitis as diagnosed radiographically. Teeth with good and
      poor coronal restorations scored clinically had apical periodontitis in 31.1 and
      36.8%, respectively; this difference was not statistically significant. The
      quality of the coronal restorations scored radiographically had a statistically
      significant influence on the periapical condition (P<0.001) with apical
      periodontitis in 23.8 and 49.1%, respectively, for acceptable and unacceptable
      restorations. Marginal decay did not influence the periapical status. Teeth
      restored without a base under the coronal filling had apical periodontitis in
      41.3%, whereas teeth with a base had significantly less (P<0.005) apical
      periodontitis (25.9%). Composite-restored teeth exhibited apical periodontitis in
      40.5% of cases whilst amalgam-restored teeth had apical periodontitis in 28.4% of
      cases; this difference was statistically significant (P<0.01). Root-canal posts
      had no influence on periapical health. The length and homogeneity of the root
      canal fillings had a significant influence (P<0.01 and P<0.001, respectively) on
      the presence of apical periodontitis, as well as the quality of the coronal
      restoration scored radiographically (P<0.001). CONCLUSION: The importance of a
      good coronal restoration, as well as of a good root filling should be emphasized
      as the technical quality of both influencing the periapical status.

PMID- 12196222
TI  - Periapical status, prevalence and quality of endodontic treatment in an adult
      French population.
AB  - AIM: The aim of this study was to determine the periapical status and the quality
      of root-canal treatment amongst an adult population attending the dental school
      in Nice, France during 1998. METHODOLOGY: Patients who attended the dental school
      for the first time during 1998 were included. Panoramic radiographs, taken by a
      trained radiology assistant, were used in this study. The periapical areas of all
      teeth with the exception of third molars, were examined and the technical quality
      of root fillings were evaluated for both apical extension and density.
      Statistical analyses were conducted using anova, Chi-square, Fisher's PLSD and
      Cohen's Kappa tests. RESULTS: The survey involved 344 patients: 180 females and
      164 males. Males had significantly fewer natural remaining teeth than females
      (P<0.03). Similarly, the average number of root-filled teeth was lower for males
      (P<0.01). Nonroot-filled teeth (n=6126) had significantly fewer signs of
      periapical pathology than root-filled teeth (n=1429) (1.7% vs. 31.5%, P<0.0001).
      The majority of root fillings were poorly executed. There was a significant
      correlation between the presence of periapical pathology and inadequate root
      canal fillings (P<0.001). CONCLUSIONS: The results of the present study indicate
      that many root-canal treatments were technically unsatisfactory in terms of
      quality and treatment outcome. There is a need for endodontic retreatment in the
      population examined.

PMID- 12196223
TI  - Combinations of bacterial species in endodontic infections.
AB  - AIM: This study was undertaken to investigate combinations of bacteria found in
      root-canal infections of teeth with periapical bone destruction without clinical
      signs and symptoms. METHODOLOGY: Endodontic samples from 58 root canals were
      cultured anaerobically and microorganisms were counted and identified. Eighty-one
      combinations of microorganisms were found and tested for a symbiotic relationship
      using the Fisher's exact test and Odds ratio calculation. RESULTS: All samples
      contained microorganisms with a median CFU mL(-1) of 8x10(4) per sample. Strict
      anaerobic species accounted for 87% of the microflora. The most prevalent
      bacteria were Prevotella intermedia, Peptostreptococcus micros and Actinomyces
      odontolyticus, present in 33, 29 and 19%, respectively, of the cultured canals. A
      significant relationship (P<0.05) and an Odds ratio >2 were found between P.
      intermedia and P. micros, P. intermedia and P. oralis, A. odontolyticus and P.
      micros, Bifidobacterium spp. and Veillonella spp. CONCLUSIONS: These results
      indicate that endodontic pathogens do not occur at random but are found in
      specific combinations.

PMID- 12196224
TI  - Diagnosing periapical lesions--disagreement and borderline cases.
AB  - AIM: The aim of this paper is to present a selection of disagreement and
      borderline cases from a methodological study on the radiographic diagnosis of
      periapical disease. METHODOLOGY: Thirty-two roots, 12% of the material in an
      earlier study, were subjected to joint discussion because of diagnostic problems.
      The aim was consensus. Six cases representing different teeth/roots illustrating
      typical problems are presented. RESULTS: The varying morphology of apical areas
      and varying density of surrounding bone present a number of challenges. Even so,
      the joint discussion resulted in an agreement for all the cases. Twenty-five
      diagnoses were established and seven cases were not diagnosed owing to
      substandard radiographs. CONCLUSION: A detailed analysis of the periodontal
      ligament space, the lamina dura, trabecular pattern and bone marrow spaces is
      mandatory for the radiographic diagnosis of periapical disease

PMID- 12196225
TI  - Prevalence of different periapical lesions associated with human teeth and their
      correlation with the presence and extension of apical external root resorption.
AB  - AIM: The aim of this study was to determine the prevalence of various periapical
      pathologies and their association with the presence and extent of apical external
      inflammatory root resorption in human teeth. METHODOLOGY: One hundred and four
      root apices from extracted teeth with periapical lesions were examined. Semi
      serial sections of soft tissue lesions were stained with HE. The lesions were
      classified as noncystic or cystic, each with different degrees of acute
      inflammation: 0, 1, 2 and 3, increasing in severity. The root apices were
      analysed by SEM. External root resorption was classified according to site, as
      periforaminal or foraminal, and the extension of the resorbed area graded in
      increasing area as 0, 1, 2 or 3. RESULTS: Cysts accounted for 24.5% of the
      samples, 84% of which were associated with marked inflammation. The most
      prevalent diagnosis was noncystic periapical abscess with varying degrees of
      severity (63.7%). Periapical granuloma was not a frequent finding. SEM analysis
      showed that 42.2% of the root apices had periforaminal resorption extending over
      50% of their circumference. When the foraminal resorption was evaluated, 28.7%
      had resorption affecting >50% of the periphery. Only 8.9% of the samples showed
      no periforaminal or foraminal resorption. CONCLUSIONS: In the sample of extracted
      teeth investigated, 24.5% of the periapical lesions were cysts. Most periapical
      lesions (84.3%) displayed acute inflammation, whether cystic or not.
      Periforaminal resorption was present in 87.3% of the cases, and foraminal
      resorption in 83.2%. Periforaminal and foraminal resorptions were independent
      entities. There was no association between external root resorption and the
      nature of the periapical lesions.

PMID- 12196227
TI  - The city and the bush: where is the best place for radiotherapy departments?

PMID- 12196226
TI  - In vivo fracture of a new rubber-dam clamp.
AB  - AIM: This study was carried out to investigate the reasons for fracture of a new
      rubber-dam clamp used for the first time. SUMMARY: The fractured surfaces of the
      broken clamp were studied with optical microscopy. Characteristic surface
      patterns of tensile fracture were identified. Cracks originated from the groove
      of letter D mechanically engraved on the inner surface of the clamp bow, and
      developed with high velocity (unstable crack growth rate) leading to catastrophic
      fracture. This behaviour was attributed to the residual stresses introduced by
      the labelling technique due to local thermal alterations. KEY LEARNING POINTS:
      The labelling technique used to number clamps may be implicated with catastrophic
      failure. Dentists should be aware that even new clamps can fracture. It is
      important that clamps are secured to prevent inhalation of metal fragments,
      should catastrophic failure occur.

PMID- 12196228
TI  - Computed tomography perfusion imaging in acute stroke.
AB  - The development of thrombolytic and neuroprotective agents for the treatment of
      acute stroke has created an imperative for improved imaging techniques in the
      assessment of acute stroke. Five cases are presented to illustrate the value of
      perfusion CT in the evaluation of suspected acute stroke. To obtain the perfusion
      data, a rapid series of images was acquired without table movement following a
      bolus of contrast medium. Cerebral blood flow, cerebral blood volume and mean
      transit time were determined by mathematically modelling the temporal changes in
      contrast enhancement in the brain and vascular system. Pixel-by-pixel analysis
      allowed generation of perfusion maps. In two cases, CT-perfusion imaging usefully
      excluded acute stroke, including one patient in whom a low-density area on
      conventional CT was subsequently proven to be tumour. Cerebral ischaemia was
      confirmed in three cases, one with an old and a new infarction, one with a large
      conventional CT abnormality but only a small perfusion defect, and one
      demonstrating infarct and penumbra. Perfusion CT offers the ability to positively
      identify patients with non-haemorrhagic stroke in the presence of a normal
      conventional CT, to select those cases where thrombolysis is appropriate, and to
      provide an indication for prognosis.

PMID- 12196229
TI  - 2002 Australian radiology workforce report.
AB  - This paper describes the current status of radiologist provision in Australia,
      and explores issues relating to its current adequacy, as well as analysing
      projections of supply and requirements, and their balancing. Data are drawn from
      several sources including the results of the Royal Australian and New Zealand
      College of Radiologists Workforce Survey 2000, and the report of the Australian
      Medical Workforce Advisory Committee Radiology Working Party 2001. The main
      conclusions to be drawn are that: (i) there is a current shortfall of radiologist
      supply in Australia; (ii) future requirements (taking all factors into
      consideration) are expected to grow at a greater rate than projected supply
      (based on the status quo); and (iii) supply of radiologists should therefore be
      increased. These conclusions are roughly in line with those from other countries,
      such as the UK, Canada and USA. Radiologists practising in Australia also appear
      to have relatively high productivity, including by some international
      comparisons. These findings are presented in the context of current issues in
      Australian medical imaging, including provider consolidation and corporatization,
      globalization and funding.

PMID- 12196230
TI  - Comparison of cost and outcome of endovascular and neurosurgical procedures in
      the treatment of ruptured intracranial aneurysms.
AB  - Endovascular techniques for the treatment of intracranial aneurysms have gained
      rapid acceptance in some countries as an alternative to conventional
      neurosurgical treatment. The International Subarachnoid Aneurysm Trial (ISAT) is
      the first multicentre prospective randomized trial comparing neurosurgery with
      endovascular coil (Guglielmi detachable coil) treatment of acute subarachnoid
      haemorrhage. The cost and outcome of endovascular procedures was compared with
      neurosurgical procedures in the treatment of ruptured intracranial aneurysms
      within the context of the ISAT. Two groups of patients (Endovascular group with
      10 patients and the Neurosurgical group with 12 patients) were drawn from
      admissions to Royal Perth Hospital and Sir Charles Gairdner Hospital, Perth,
      Western Australia, as detailed in the ISAT trial protocol. Data were collected in
      the following categories: patient, procedure, hospitalization, morbidity and
      mortality. While the endovascular procedure tended to be the more expensive in
      terms of the cost of consumables, this expense was more than compensated by
      savings in staffing costs, and the period and cost of hospitalization. Following
      an endovascular procedure, patients tended to return to normal activity or paid
      employment sooner and have a favourable functional outcome compared with patients
      following a neurosurgical procedure.

PMID- 12196231
TI  - Giant fibroadenoma of the breast in an Arab population.
AB  - In a retrospective study of giant breast masses over a period of 20 years (1980
      2000), we encountered 18 patients with fibroadenomas. Most of them were
      adolescents and young adults. The bimodal age incidence seen in Caucasians was
      not observed. The masses ranged from 6 to 15 cm in size and in the youngest
      patient, they were bilateral. All 18 patients were examined by mammography and 10
      of them by ultrasonography (US) as well. The right breast was involved in 12
      patients and the left in six. The diagnosis was confirmed pathologically in all
      patients, by excision biopsy in 17 patients and by fine needle aspiration
      cytology and excision biopsy in one patient. The radiological findings were the
      same as those previously described. All patients were treated by simple
      enuculation. There was only one recurrence over a follow-up period from 2 months
      to 3 years.

PMID- 12196232
TI  - Quality assurance and radiofrequency heating.
AB  - This paper proposes an inexpensive means of assessing radiofrequency (RF) power
      deposition in a magnet. This is particularly important at 3T where sequences
      approach Food and Drug Administration approved RF limits. It will also be of
      interest to operators at 1.5 T as part of their ongoing quality assurance
      programs. At 3T, we found that the RF power deposited in the magnet was less than
      that read by the MR power monitor.

PMID- 12196233
TI  - Mammographic features of tuberculous axillary lymphadenitis.
AB  - The clinical and mammographic findings of 10 patients with pathologically proven
      tuberculous axillary lymphadenitis were reviewed. The cases were identified from
      10 173 mammograms performed over 6 years at Maharaj Nakorn Chiang Mai University
      Hospital. The 10 patients were aged 31-65 years. All cases were initially
      diagnosed to have breast carcinoma with axillary nodal metastases. Eight patients
      presented with axillary swelling, while two presented with breast enlargement.
      None of these cases had a palpable breast mass. Associated supraclavicular,
      cervical or groin nodes were found in seven cases, and two patients had evidence
      of pulmonary tuberculosis. All lesions were unilateral, affecting the right side
      in eight cases and left side in two cases. On mammogram, the axillary nodes were
      enlarged and homogeneously dense. The nodes were sized 2.5-5 cm. Nodal margins
      were variable. Some nodes were matted. Macrocalcifications were noted in three
      cases. Ipsilateral breast oedema without mass or microcalcifications was present
      in two cases. Patients with tuberculous axillary lymphadenitis have large
      homogeneously dense nodes with either well- or ill-defined margins. It is
      impossible to differentiate tuberculous from malignant nodes. The presence of
      macrocalcifications might suggest tuberculous axillary lynphadenitis. Biopsy of
      enlarged axillary nodes is necessary to determine its aetiology.

PMID- 12196234
TI  - Treatment of iatrogenic femoral artery false aneurysms with ultrasound-guided
      thrombin injection.
AB  - The aim of this paper is to review our results of treating iatrogenic
      pseudoaneurysms of the femoral artery with ultrasound-guided thrombin injection.
      A retrospective review was carried out of all patients referred for this
      procedure over a 1-year period from December 1999 to December 2000. Forty-five
      patients were referred and, of these, 44 were eligible for this treatment, with
      300-2500 units of thrombin being injected directly into the false aneurysms under
      ultrasound guidance. The procedure was well tolerated with no patients requiring
      sedation or analgesia. There was a primary success rate of 95%, although in four
      of the patients, there was recurrence on repeat ultrasound performed 2-5 days
      post-procedure and a second injection of thrombin was required for permanent
      thrombosis to be achieved. No complications relating to the procedure occurred.
      Our results confirm increasing evidence in the published research that thrombin
      injection of femoral artery false aneurysms is a safe and effective treatment.

PMID- 12196235
TI  - Multiple sclerosis in a radiosensitive family with low levels of the ATM protein.
AB  - Multiple sclerosis (MS) is a chronic neurological disease of the central nervous
      system (CNS) characterized by demyelination associated with progressive
      disability. The mechanisms underlying the pathogenesis of MS remain a mystery.
      The highly pleiotropic syndrome known as ataxia telangiectasia (A-T) overlaps
      with MS in that it also presents with demyelination in the CNS. Whether
      demyelination in MS or in A-T is initiated through neuronal degeneration or
      immune dysfunction is not yet known. However, unlike MS, the underlying cause of
      A-T is known to result from mutations in the A-T gene (ATM) that often result in
      the complete loss of ATM protein and loss/gain of function. ATM is implicated in
      neurological degeneration, particularly in the cerebellum, cellular apoptosis,
      immunodeficiency, double stranded deoxyribonucleic acid (DNA) rejoining, VDJ
      antibody recombination, tumour suppression, particularly T-lymphoid malignancies,
      signal transduction, cell-cycle control and cellular radiohypersensitivity. In
      this study, we describe a case of MS in a family with cellular radiosensitivity
      and abnormally low postinduction levels of the ATM protein. Defective DNA
      repair/rejoining may impact on autoimmunity.

PMID- 12196236
TI  - Waiting for radiation therapy: does it matter?
AB  - The aim of this study was to determine the direct and indirect effects of
      prolonged waiting times for radiation therapy. We used the Medline, CancerNet and
      EMBASE databases to search the international research using the keywords
      radiotherapy, waiting times and delay. The negative effects of prolonged waiting
      times for radiation therapy can be broken down into direct and indirect effects.
      Direct effects include tumour control factors and patient factors. Indirect
      effects include changes in referral patterns and change in management of tumours.
      The precise effects of prolonged waiting times for radiation therapy are
      difficult to define. Evidence exists for some tumour sites, such as postoperative
      head and neck, small-cell lung cancer and high-grade cerebral gliomas, that
      tumour control might be adversely affected. The effect on other tumour sites is
      less established. Patient factors are likely to be consistent across all tumour
      types and indirect effects are hard to quantify.

PMID- 12196237
TI  - Management preferences following radical inguinal orchidectomy for Stage I
      testicular seminoma in Australasia.
AB  - A survey to evaluate the preferred patterns of management of Stage I seminoma was
      conducted during March 2001. The questionnaire was distributed by the Royal
      Australian and New Zealand College of Radiologists to all qualified radiation
      oncologists, 74 out of 170 responded. All performed a staging CT scan of the
      abdomen and pelvis. Thoracic imaging consisted of either chest X-ray (29%) or
      chest CT (38%) while 33% performed both. Fifty-four percent of radiation
      oncologists discussed surveillance with their patients but estimated that 5% or
      less would choose this option. The most commonly prescribed dose was 25 Gy in 15
      or 20 fractions (79%). Sixty-five percent of respondents treated the para-aortic
      (PA) nodes alone. Forty-two of 48 clinicians treating the PA field reported a
      change in practice after publication of the Medical Research Council study in
      1999. Of these, 40 and 23% perform CT scans of the pelvis annually and every 6
      months. Thirty-one percent did no follow-up CT scan. Compared to a similar survey
      from North America, we are more likely to use PA fields and less likely to
      discuss surveillance. As in the USA, and in contrast to Canada, few patients
      choose surveillance. There is no consensus regarding the frequency of follow-up
      scans in either North America or Australasia.

PMID- 12196238
TI  - Intensity-modulated radiation therapy: First reported treatment in Australasia.
AB  - Intensity-modulated radiation therapy (IMRT) is an exciting new advance in the
      practice of radiation oncology. It is the use of non-uniform radiation beams to
      achieve conformal dose distributions. As a result of the high initial capital
      costs and the time and complexity of planning, IMRT is not yet a widely available
      clinical treatment option. We describe the process involved in applying this new
      technology to a case of locally advanced nasopharyngeal cancer.

PMID- 12196239
TI  - Geographic delivery models for radiotherapy services.
AB  - The study described here was undertaken to quantify the societal cost of
      radiotherapy in idealized urban and rural populations and, hence, to generate a
      measure of impediment to access. The costs of centralized, distributed
      comprehensive and satellite radiotherapy delivery formats were examined by
      decomposing them into institutional, productivity and geographical components.
      Our results indicate that centralized radiotherapy imposes the greatest financial
      burden on the patient population in both urban and rural scenarios. The financial
      burden faced by patients who must travel for radiotherapy can be interpreted as
      one component of the overall impediment to access. With advances in remote
      monitoring systems, it is possible to maintain technical quality while enhancing
      patient access. However, the maintenance of professional competence will remain a
      challenge with a distributed service-delivery format.

PMID- 12196240
TI  - Petrous apex arachnoid cyst extending into Meckel's cave.
AB  - A rare case of arachnoid cyst involving the petrous apex with an unusual clinical
      presentation has been described with special emphasis in the imaging features and
      importance of accurate presurgical diagnosis. Differentiation from the other
      benign lesions involving the petrous apex and the role of newer MR techniques in
      the diagnosis of these lesions has been highlighted.

PMID- 12196241
TI  - Segmental hyperattenuation in the liver as a result of right hepatic vein
      thrombosis: an unusual complication of central venous catheterization.
AB  - Liver perfusion disorder secondary to hepatic vein occlusion is not often
      reported. This abnormality might be caused by invasion of the hepatic veins by
      tumour or compression by a large right adrenal mass. We present an unusual cause
      of hepatic perfusion disturbance due to right hepatic vein thrombosis resulting
      from inadvertent hepatic venous catheterization. On contrast-enhanced CT, the tip
      of a central venous catheter extended into the right hepatic vein, which was
      thrombosed. A sharply marginated wedge-shaped hyperdense region was demonstrated
      in the right lobe of the liver, thought to represent a compensatory increase in
      arterial flow to the affected territory.

PMID- 12196242
TI  - Gallium avid breast carcinoma.
AB  - Primary breast carcinomas are generally thallium (Tl-201) avid but uncommonly
      accumulate gallium (GA-67). Therefore, GA-67 scans are not routinely performed in
      patients with suspected breast cancer. We report a rare case of a primary breast
      carcinoma with bone marrow metastases where the primary lesion was GA-67 avid but
      did not accumulate Tl-201. The case also illustrated an unusual presentation of
      aggressive metastatic breast adenocarcinoma with pancytopenia or bone marrow
      failure. The extensive bone marrow metastases of the primary breast carcinoma
      were evident on both the Tl-201 and GA-67 scans.

PMID- 12196243
TI  - Toxic leucoencephalopathy after heroin inhalation.
AB  - The neurological symptoms after inhalation of contaminated heroin vapour could be
      the result of toxic leucoencephalopathy. We describe a case of a 53-year-old man
      who has typical symptoms and MR features of toxic leucoencephalopathy.

PMID- 12196244
TI  - Cervical osteochondroma as a cause of spinal cord compression in a patient with
      hereditary multiple exostoses: Computed tomography and magnetic resonance imaging
      findings.
AB  - Spinal cord compression is a rare but extremely serious complication of
      hereditary multiple exostoses (HME). Imaging of the spine is important for
      surgical planning and follow up. We present CT and MR findings in a male patient
      with HME who developed spinal cord compression from a cervical osteochondroma.
      Complete recovery was achieved following surgery.

PMID- 12196245
TI  - Systemic to portal shunting following vena cava obstruction: Computed tomography
      and venographic appearances.
AB  - Obstruction of the inferior or superior vena cava normally leads to the formation
      of a well-described and consistent pattern of collateral venous pathways. We
      present the angiographic and CT features of the unusual development of systemic
      to portal venous shunting in two cases with central vein obstruction.

PMID- 12196246
TI  - Magnetic resonance imaging findings in an unusual case of atlanto axial
      dislocation and vertebral artery-vein fistulas in a patient of neurofibromatosis
      1.
AB  - Vertebral arteriovenous fistulas are uncommon in neurofibromatosis. We describe
      MRI findings of a patient with an unusual association of bilateral vertebral
      arteriovenous fistulas with an atlantoaxial dislocation in the setting of
      neurofibromatosis.

PMID- 12196247
TI  - Hypertensive encephalopathy.
AB  - The case report of a patient with hypertensive encephalopathy is presented here.
      The findings of reversible bilateral thalamic changes on T2-weighted MR imaging
      is an atypical manifestation of the reversible posterior leucoencephalopathy
      syndrome (RPLS), which is the neuroradiological correlate of hypertensive
      encephalopathy. The importance of prompt and accurate diagnosis of hypertensive
      encephalopathy / RPLS is stressed.

PMID- 12196248
TI  - Percutaneous retrieval of a proximally migrated common bile duct endoprosthesis
      from the right anterior duct.
AB  - Common bile duct (CBD) endoprostheses that are inserted at endoscopy are in
      routine clinical use to decompress the obstructed biliary tract. This case
      describes the proximal migration of a CBD endoprosthesis into the right anterior
      duct. An attempt at endoscopic retrieval failed. The endoprosthesis was retrieved
      by a percutaneous transhepatic approach using an Amplatz goose-neck snare. To the
      best of our knowledge, use of the Amplatz goose-neck snare has not been reported
      for this application.

PMID- 12196249
TI  - ATM induction insufficiency in a radiosensitive breast-cancer patient.
AB  - The ataxia telangiectasia (A-T) gene (ATM) is a dominant breast cancer gene with
      tumour suppressor activity. ATM also regulates cellular sensitivity to ionising
      radiation (IR) presumably through its role as a facilitator of DNA repair. In
      normal cells and tissues the ATM protein is rapidly induced by IR to
      threshold/maximum levels. The kinase function of the ATM protein is also rapidly
      activated in response to IR. The fact that women carriers of ATM mutations can
      have an increased risk of developing breast cancer and that many sporadic breast
      tumours have reduced levels of the ATM protein broadens the scope of ATM's tumour
      suppressor within the breast. This report describes the downregulation of ATM
      protein levels in a radiosensitive breast cancer patient. Postinduction ATM
      levels were up to tenfold lower in the patient's fresh tissues compared to normal
      controls. These results might indicate a much broader role for ATM anomalies in
      breast cancer aetiology.

PMID- 12196250
TI  - Mycosis fungoides involving the oral cavity.
AB  - Mycosis fungoides is a malignant T-cell lymphoproliferative disease with a
      predilection for cutaneous involvement. Extracutaneous disease is uncommon and
      oral mucosal involvement is rare. We describe a case of mycosis fungoides
      involving the hard palate treated with radiotherapy. The relevant literature on
      this topic is reviewed.

PMID- 12196251
TI  - Concomitant diminishing magnetization-transfer effect and increasing choline
      level in radiation-induced temporal-lobe changes.
AB  - This article reports on the use of both magnetization-transfer (MT) imaging and
      1H-MR spectroscopy in two cases of bilateral temporal-lobe changes after
      radiation therapy for nasopharyngeal carcinoma. In the first case, the following
      patterns were noted: (i) although the temporal lobes appeared relatively normal
      on T2-weighted MR imaging, corresponding MT imaging clearly showed signal
      abnormalities (decreased MT effect) consistent with alterations in macromolecular
      structure; and (ii) concomitant strongly elevated choline on 1H-MR spectroscopy
      was observed, and this is associated with metabolic changes in cell membranes.
      The second case presented similar characteristics. In addition, there was an
      increased lactate signal and T2 signal changes in keeping with established
      oedema. Both MT and proton-spectroscopic findings were consistent with postulated
      pathophysiological features of radiation injury, but their specificity for this
      condition remains unclear. Magnetization-transfer imaging, and possibly 1H-MR
      spectroscopy, might be sensitive techniques for the early detection of late
      radiation injury.

PMID- 12196252
TI  - RE: Singular honour for Dr Harold Fabrikant.

PMID- 12196253
TI  - RE: Awasthi M, Narlawar R, Hira P, Shah P. Fetus in fetu. Rare cause of a lump in
      an adult's abdomen. Australas Radiol 2001;45: 354-56.

PMID- 12196254
TI  - RE: Palliative brain radiotherapy regimen.

PMID- 12196255
TI  - RE: Corry J, Hope G, Cramb J et al. Intensity-modulated radiation therapy: first
      reported treatment in Australasia. Australas Radiol 2002; 46: 285-289.

PMID- 12196260
TI  - Morphological changes in the sciatic nerve of diabetic rats treated with low
      molecular weight heparin OP 2123/parnaparin.
AB  - This study points out the early alterations that affect the sciatic nerve of rats
      with experimentally induced diabetes. It emphasizes the advantages deriving from
      treatment with low molecular weight heparin (LMWH) OP 2123/parnaparin and
      correlates these findings with observations emerging from a review of the
      relevant literature. In fact, the number and diameter of the capillaries within
      the sciatic nerve of diabetic rats appear to be increased consistent with a
      microangiopathy (the main characteristic of which is the fragility of new
      vessels), that is related to the evolution of diabetes in humans and animals. Our
      results suggest a possible therapeutic role for OP 2123/parnaparin in both
      diabetic neuropathy and microangiopathy, frequent complications of diabetes.

PMID- 12196261
TI  - Is the male dog comparable to human? A histological study of the muscle systems
      of the lower urinary tract.
AB  - Because of their superficial anatomical resemblance, the male dog seems to be
      suitable for studying the physiologic and pathological alterations of the bladder
      neck of human males. The present study was carried out to compare and contrast
      the muscular anatomy of the male dog lower urinary tract with that of humans. The
      complete lower urinary tract, including the surrounding organs (bulb of penis,
      prostate, rectum and musculature of the pelvic floor) were removed from adult and
      newborn male dogs and histologically processed using serial section technique.
      Based on our own histological investigations, three-dimensional (3D)-models of
      the anatomy of the lower urinary tract were constructed to depict the
      corresponding structures and the differences between the species. The results of
      this study confirm that the lower urinary tract of the male dog bears some
      anatomical resemblance (musculus detrusor vesicae, prostate, prostatic and
      membranous urethra) to man. As with human males, the two parts of the musculus
      sphincter urethrae (glaber and transversostriatus) are evident in the canine
      bladder neck. Nevertheless, considerable differences in formation of individual
      muscles should be noted. In male dogs, no separate anatomic entity can be
      identified as vesical or internal sphincter. The individual course of the ventral
      and lateral longitudinal musculature and of the circularly arranged smooth
      musculature of the urethra is different to that of humans. Differences in the
      anatomy of individual muscles of the bladder neck in the male dog and man suggest
      that physiological interpretations of urethral functions obtained in one species
      cannot be attributed without qualification to the other.

PMID- 12196262
TI  - Comparative functional morphology of the masticatory apparatus in the long
      snouted crocodiles.
AB  - The masticatory muscles and their related structures of the skull were observed
      in the Indian gavial (Gavialis gangeticus), the false gavial (Tomistoma
      schlegelii), and the African slender-snouted crocodile (Mecistops cataphractus)
      to detail some morphological differences in comparison with the other crocodile
      species, and to compare and elucidate the functional strategy of themasticatory
      apparatus in these long-snouted species. The Musculus pterygoideus posterior was
      relatively smaller in the three species compared with many short-snouted
      crocodiles. It suggests that the masticatory power in fish-eating long-snouted
      species is not so high as in the short-snouted crocodiles, while the masticatory
      muscles were morphologically different among the three long-snouted species as
      follows. The M. pterygoideus posterior of the false gavial was extended in the
      lateral side of the lower jaw unlike the Indian gavial. The M. pseudotemporalis
      and the Fenestra supratemporalis were largely developed in the Indian gavial,
      however we suggest that the other two species possess the weak bundles in this
      muscle. The false gavial and the African slender-snouted crocodile have the
      pterygoid bone well-developed extending dorso-ventrally and it is suggested that
      the M. adductor mandibulae posterior attached to the pterygoid bone may be much
      larger than the Indian gavial. These data morphologically clarify the masticatory
      mechanism in the long-snouted crocodiles different from the short-snouted
      species, and demonstrate that the evolutional strategy to share the functional
      role in the masticatory muscles have been differently established between the
      Indian gavial and the other two species. We also obtained the morphological data
      in the fossil skull of the Machikane crocodile (Toyotamaphymeia machikanense) and
      concluded from the fossil characters that the considerable developments of the
      M.pterygoideus posterior and the M.pseudotemporalis in this species had not
      morphologically been consistent with both the Indian and false gavials.

PMID- 12196263
TI  - Morphological and biochemical aspects of apoptosis, oncosis and necrosis.
AB  - Recent investigations have demonstrated the need for a precise differentiation of
      various forms of cell death such as apoptosis, oncosis, necrosis and programmed
      cell death. Apoptosis is marked by cellular shrinking, condensation and
      margination of the chromatin and ruffling of the plasma membrane with eventually
      breaking up of the cell in apoptotic bodies. Cell death marked by cellular
      swelling should be called oncosis, whereas the term necrosis refers to the
      morphological alterations appearing after cell death. Apoptosis and oncosis are
      therefore pre-mortal processes, while necrosis is a post-mortal condition. The
      term programmed cell death refers to the 'fixed' pathway followed by dying cells,
      whether or not with the characteristic morphology of apoptosis. Three mechanisms
      are actually known to be involved in the apoptotic process: a receptor-ligand
      mediated mechanism, a mitochondrial pathway and a mechanism in which the
      endoplasmic reticulum plays a central role. All three mechanisms activate
      caspases which are responsible for the characteristic morphological changes
      observed during apoptosis. A review of the different methods used for detecting
      apoptotic cells demonstrates that most of these techniques are not entirely
      specific.

PMID- 12196265
TI  - Brain selenium accumulation in rat pups of selenium supplemented mothers.
AB  - Selenium is essential for normal mammalian development. Being a component of
      antioxidant enzyme, glutathione peroxidase, it plays a major role in protecting
      the cells from free radical damage. The level of glutathione peroxidase was
      directly related to the amount of selenium present in various tissues and organs.
      A decrease in selenium leads to various pathological changes in humans as well as
      in various laboratory animals. The aim of the present study was to understand
      whether there is an increase in the level of selenium in different brain regions
      of rat pups whose mothers were supplemented with selenium, either 2 or 4 mg/l of
      their drinking water throughout the period of their pregnancy. There was a
      significant increase in the level of selenium in the cerebellum, cortex and
      hypothalamic and hippocampal tissues of selenium supplemented mothers as compared
      with those of non-supplemented mothers. The brain stem of these animals did not
      show any significant difference in the level of selenium. Furthermore, the
      differences in the level of selenium between the rat pups of 2 mg/l selenium
      supplemented mothers and 4 mg/l selenium supplemented mothers were not
      statistically significant. These studies suggest that supplementation of selenium
      to mothers during the period of their pregnancy can selectively increase the
      level of this trace element in different brain regions. Further studies are
      necessary to understand the significance of selective accumulation of selenium in
      specific brain regions on brain development and function.

PMID- 12196264
TI  - Histological thin-sections: a method for the microscopic study of teeth in
      Spanish red deer (Cervus elaphus hispanicus).
AB  - A method to obtain thin histological sections (4-5 microm thick) from teeth,
      using a conventional microtome, is described for incisors, molars and canines
      from Spanish red deer (Cervus elaphus hispanicus). Decalcifying solutions of
      formic acid and nitric acid at different concentrations were ineffective. This
      was not the case for a solution of 14% hypochloric acid and polyvinylpyrrolidone
      (TBD-1(R) of Shandon). However, the time needed to complete decalcification was
      longer than the time estimated by other authors. Incisors required between 4 and
      6 days, molars between 7 and 15 days, and canines between 8 and 12 days. The
      preparation of histological thin-sections from teeth with a conventional
      microtome, required some training or prior specialization, because most of
      defective or lost material occurred during the preliminary stage of the study.
      However this technique is inexpensive enough to be implemented in any
      histological laboratory. The preparations obtained are suitable for growth mark
      observation in dentine and in cementum for dating studies. Nevertheless, they are
      not suitable for enamel change studies, because the enamel is completely
      destroyed during the decalcifying process.

PMID- 12196266
TI  - Post-natal development in the linear and tric morphometrics of the camelidae
      skull.
AB  - The craniometric measurements in addition to the skull, cranial and facial
      indices undertaken in the immature and mature male Camelus dromedarius of the
      Malha phenotype (black) were: the skull length (35.99 cm), maximum width of
      neurocranium (11.33 cm), cranial length (15.45 cm), maximum zygomatic width
      (14.81 cm), viscerocranial length (20.55 cm), skull index (41.13), cranial index
      (73.70), facial index (72.31), cranial volume (231.73 ml) and skull weight
      (795.70 g) were measured in the immature camels. In the mature camels, the skulls
      gave the following measurements: the skull length (50.53 cm), maximum width of
      neurocranium (15.96 cm), cranial length (21.93 cm), maximum zygomatic width
      (22.75 cm), viscerocranial length (28.60 cm), skull index (45.06), cranial index
      (72.99), facial index (79.83), cranial volume (310.80 ml) and skull weight
      (2598.31 g). The results of a total of 30 skulls of immature and mature Malha
      camel revealed that all the measurements increased with age whereas the cranial
      index was the only parameter for which a decreased value was recorded. The
      anterior basicranial angle averaged about 203 degrees in the immature animal to
      increase to an insignificant value of 204 degrees in the mature camel skull.
      Similarly, the posterior basicranial angle did not exhibit a significant
      difference between the immature and mature values, which ranged between 110
      and112 degrees,respectively.

PMID- 12196267
TI  - An immunohistochemical study of the organization of ganglia and nerve fibres in
      the mucosa of the porcine intestine.
AB  - In order to elucidate the organization of the enteric nervous system in the
      mucous plexus, wholemounts from six intestinal regions in six pigs were studied
      by vasoactive intestinal peptide, substance P, nitric oxide synthase and
      neurofilament proteins immunohistochemistry. The mucous plexus of both large and
      small intestine contained ganglia and isolated neurons. They were many and
      comparably larger in the caecum and colon, few in the ileum, and fewer and
      smaller in the jejunum. The mucous plexus was subdivided into the lamina
      muscularis mucosae and lamina proprial subplexuses, and based on location the
      latter was subdivided further in order to clarify their variations with respect
      to the amount, sizes and shapes of ganglia and neurons, sizes and orientation of
      nerve strands and immunoreactivities. Ganglia were situated at different
      topographical levels in the lamina muscularis mucosae subplexus, outer proprial
      and interglandular proprial meshworks in the lamina proprial subplexus with the
      majority of ganglia occurring in the outer proprial meshwork. The mucous plexus
      in the intestine of the pig is thus a ganglionated plexus showing marked
      segmental variation in the amount of intramucosal ganglia and isolated nerve
      cells. These new observations, calls for a re-examination of the mucous plexus to
      elucidate the regulatory mechanisms of importance in mucosal functions and
      consideration of the mucous plexus in the intestine of the pig to be one of the
      major ganglionated plexuses.

PMID- 12196268
TI  - Morphological studies on the heart ventricle of African catfish (Clarias
      gariepinus).
AB  - The histological and ultrastructural characteristics of the heart ventricle in
      Clarias gariepinus (African catfish) has been studied by light microscopy and
      transmission electron microscopy. The ventricle of the heart has a saccular shape
      and the myocardial wall consists of an outer thin compact myocardium and an inner
      well-developed spongy myocardium. The myocardial layer has small myocytes,
      interstitial spaces and blood vessels. The myocytes are the major constituents of
      the ventricular wall. They are long cells, with large nuclei, and predominantly
      euchromatin. The sarcoplasmic reticulum of the ventricular myocytes consists of a
      network of tubules and subsarcolemmal cisternae oriented mainly along the
      longitudinal axis of the myofibrils. In contrast to the ventricular structure of
      other fish species described in the literature (Greer-Walker et al., 1985;
      Santer, 1985; Sanchez-Quintana et al., 1995, 1996), the African catfish, a
      freshwater sedentary fish recently introduced in neotropical climatic
      environments, showed a saccular ventricle that consisted of two muscle layers, a
      thin compact layer with large vessels and a developed spongy layer. The
      ultrastructure of the ventricular myocardium of C.gariepinus is similar to that
      of other teleosts, inclusive that of fish with other swimming habits.

PMID- 12196269
TI  - Nitric oxide signalling system in rat brain stem: immunocytochemical studies.
AB  - Nitric oxide is a free radical, which is produced in several tissues of the body
      and is thought to be the first of a new class of neural messenger molecules and a
      retrograde modulator of synaptic transmission in the brain. Nitric oxide synthase
      (NOS) is the enzyme that produces nitric oxide from the substrate l-arginine. The
      pattern of the distribution of neuronal isoform of NOS was investigated in
      neurones and fibres in the brain stem using standard immunocytochemistry. In our
      results, NOS positive neurones and processes were seen in the spinal trigeminal
      nucleus, gracile nucleus, nucleus of the solitary tract, nucleus ambiguus,
      reticular nuclei and lateral to the pyramidal tract of the medulla. In the pons,
      heavily labelled NOS containing neurones were seen in the pedunuclopontine
      tegmental nucleus, ventral tegmental nucleus and in the laterodorsal tegmental
      nucleus. The localization of neuronal NOS expressing neurones suggests a
      widespread neuromodulatory role for the nitric oxide in the central nervous
      system of rat.

PMID- 12196271
TI  - Whither chemoprevention?

PMID- 12196274
TI  - Ductal lavage and ductoscopy: the opportunities and the limitations.
AB  - Two related techniques of breast epithelial sampling have emerged in the past
      several years: ductal lavage, in which fluid-yielding nipple ducts are cannulated
      at their orifices and lavaged with saline while the breast is intermittently
      massaged; and ductoscopy, in which discharging or fluid-yielding duct orifices
      are dilated, intubated with a microendoscope, and the lumen directly visualized.
      Both of these techniques have significant potential in terms of allowing the
      repeated sampling of ductal epithelium over time and, as such, have generated
      considerable enthusiasm. However, data regarding the impact of these techniques
      on the detection of significant breast disease is very scant. It is important at
      the outset of the assessment of this new technology that breast cancer clinicians
      and clinical researchers think carefully about the standards of evidence that
      need to be met regarding the benefits of these procedures before they are widely
      adopted. In this review of the rationale and early results of these procedures,
      we attempt to define some of these evidentiary requirements.

PMID- 12196270
TI  - Increased expression of ICAM-1, VCAM-1, MCP-1, and MIP-1 alpha by spinal
      perivascular macrophages during experimental allergic encephalomyelitis in rats.
AB  - BACKGROUND: T-cells extravasation and CNS parenchyma infiltration during
      autoimmune neurodegenerative disease can be evoked by local antigen presenting
      cells. Studying the chemoattracting potential of spinal perivascular macrophages
      (SPM) during experimental allergic encephalomyelitis (EAE), we observed numerous
      infiltrates of densely-packed mononuclear cells. Apart from the poor spatial and
      optical resolution, no differentiation between the resident SPM (mabs ED1+, ED2+)
      and the just recruited monocytes/macrophages (mab ED1+) was possible. RESULTS:
      This is why we labeled SPM by injections of different fluoresecent dyes into the
      lateral cerebral ventricle before induction of active EAE. Within an additional
      experimental set EAE was induced by an intraperitoneal injection of T-cells
      specifically sensitized to myelin basic protein (MBP) and engineered to express
      the green fluorescent protein (GFP). In both experiments we observed a strong
      activation of SPM (mabs OX6+, SILK6+, CD40+, CD80+, CD86+) which was accompanied
      by a consistently increased expression of ICAM-1, VCAM-1, and the chemokines MCP
      1 and MIP-1alpha. CONCLUSION: These observations indicate that SPM play a role in
      promoting lymphocyte extravasation.

PMID- 12196277
TI  - Clinical utility of urokinase-type plasminogen activator and plasminogen
      activator inhibitor-1 determination in primary breast cancer tissue for
      individualized therapy concepts.
AB  - Invasion factors urokinase-type plasminogen activator (uPA) and its plasminogen
      activator inhibitor (PAI-1) are the only novel tumor biological prognostic
      factors validated at the highest level of evidence with regard to their clinical
      utility in breast cancer. Antigen levels of both factors present in extracts of
      primary tumor tissue are determined by standardized, quality-assured enzyme
      linked immunosorbent assays. Numerous studies showed that patients with low
      levels of uPA and PAI-1 have a significantly better survival than patients with
      high levels of either factor. Recently, these data have been validated by a
      European Organization for Research and Treatment of Cancer pooled analysis
      comprising more than 8000 breast cancer patients. The particular combination of
      both factors, uPA/PAI-1 (both low vs. either or both factors high), outperforms
      the single factors as well as other traditional prognostic factors with regard to
      risk group assessment, particularly in node-negative breast cancer. Node-negative
      breast cancer patients with low levels of uPA and PAI-1 have a very good
      prognosis and, as such, may be candidates for being spared the burden of adjuvant
      chemotherapy. In contrast, node-negative patients with high uPA/PAI-1 are at a
      substantially increased risk of relapse, comparable to that of patients with > or
      = 3 involved axillary lymph nodes. First results from a multicenter prospective
      randomized therapy trial in node-negative breast cancer (Chemo N(0)) as well as
      recent retrospective analyses indicate that these high-risk patients benefit from
      adjuvant chemotherapy. Thus, combined determination of the invasion factors uPA
      and PAI-1 supports risk-adapted individualized therapeutic strategies in patients
      with primary breast cancer, particularly in those with node-negative breast
      cancer.

PMID- 12196278
TI  - Peripheral blood c-erbB-2 expression by reverse transcriptase-polymerase chain
      reaction in breast cancer patients receiving chemotherapy.
AB  - Minimal residual disease (MRD) evaluation in breast cancer patients is a
      promising tool to improve current staging procedures. In a previous work
      employing a CK-19-based reverse transcriptase-polymerase chain reaction (RT-PCR)
      technique for MRD detection, we identified a group of women who exhibited
      persistent negativity for this assay and for whom this technique was considered
      noninformative. In order to improve the yield of MRD detection in these patients,
      we evaluated the usefulness of RT-PCR detection of c-erbB-2 expression. We were
      able to detect up to 1 MCF-7 cell (positive for c-erbB-2 expression) in a mixture
      of 1,000,000 CCRF-CEM cells (negative for c-erbB-2 expression). We evaluated the
      specificity of this technique in the peripheral-blood mononuclear cells (PBMCs)
      of 20 healthy women and found that 2 of these women were positive for c-erbB-2
      expression. In the PBMCs of a group of 16 women with breast cancer, 25% of the
      samples were positive for c-erbB-2 expression before chemotherapy. Except for
      race (P = 0.017), no other significant correlations were found, including c-erbB
      2 expression in the primary tumor by immunoperoxidase. Interestingly, in the
      subgroup of 6 patients for whom this technique was informative, we found that 80%
      of the samples obtained while on chemotherapy were negative compared to only 10%
      obtained off treatment (P = 0.017). Additionally, 2 patients for whom CK-19
      expression was noninformative had at least 1 c-erbB-2-positive sample. We
      conclude that this technique might be useful for MRD detection in breast cancer
      patients, but further studies are necessary to confirm our findings.

PMID- 12196279
TI  - Bisphosphonates: biological response modifiers in breast cancer.
AB  - Bone recurrence constitutes one third of initial sites of relapse and one half of
      distant sites of relapse at 10 years from diagnosis of breast cancer. Bone pain,
      fracture (including vertebral fracture resulting from increased bone resorption
      following chemotherapy-induced menopause), and hypercalcemia are components of
      skeletal morbidity. The pathophysiology of malignant osteopathy occurs because of
      the secretion of substances (such as parathyroid hormone-related peptide), by the
      malignant cell, which stimulate osteoclast function; this in turn feeds further
      growth, which causes a vicious cycle. Interruption of this cycle by
      bisphosphonates may inhibit the growth of malignant cells. Bisphosphonates are
      drugs that inhibit bone turnover by decreasing bone resorption. Side effects of
      bisphosphonates include upper gastrointestinal symptoms (in oral nitrogen
      containing bisphosphonates) and diarrhea (in oral non-nitrogen-containing
      bisphosphonates) and an acute phase-like reaction with intravenous (I.V.)
      pamidronate. Bisphosphonates have different molecular mechanisms of action:
      Nitrogen-containing bisphosphonates (eg, pamidronate and alendronate) inhibit the
      mevalonate-signaling pathway while the non-nitrogen-containing drugs (eg,
      clodronate) incorporate into adenosine triphosphate analogues. There is in vitro
      evidence that these drugs also possess anticancer properties. In hypercalcemia
      patients, treatment with pamidronate and zoledronate produce prompt and efficient
      normocalcemia. Intravenous pamidronate and zoledronate, oral clodronate, and
      ibandronate reduce skeletal complications in patients with bone metastases; I.V.
      pamidronate and clodronate are useful for bone pain relief. Three adjuvant
      bisphosphonate trials are discussed herein: 2 small open-label studies giving
      conflicting results and a large placebo-controlled trial of oral clodronate. This
      latter trial shows a reduction in the incidence of skeletal metastases (while the
      patients are on therapy) and an improved survival at 5 years.

PMID- 12196282
TI  - Breast conservation treatment for patients presenting with axillary
      lymphadenopathy from presumed primary breast cancer: the role of breast magnetic
      resonance imaging for staging.
AB  - Three female patients presented with malignant axillary lymphadenopathy presumed
      to be from primary breast cancer. No evidence of primary cancer was found in the
      breast on either mammography or breast magnetic resonance imaging (MRI). All 3
      patients underwent axillary lymph node dissection and systemic chemotherapy
      followed by radiation therapy to the breast and regional lymph nodes. Two
      patients remain relapse free with a follow-up of 3.7 years each. The third
      patient achieved locoregional control in the ipsilateral breast and regional
      lymph nodes but relapsed in the contralateral axilla. These 3 cases illustrate
      the potential for breast conservation treatment for patients presenting with
      axillary adenopathy from a presumed primary breast cancer but without either
      mammographic or breast MRI findings.

PMID- 12196283
TI  - The clinical effectiveness and cost-effectiveness of surgery for people with
      morbid obesity: a systematic review and economic evaluation.

PMID- 12196284
TI  - Transcription from the RAG1 locus marks the earliest lymphocyte progenitors in
      bone marrow.
AB  - Viable Lin(-) CD27(+) c-kit(Hi) Sca-1(Hi) GFP(+) cells recovered from
      heterozygous RAG1/GFP knockin mice progressed through previously defined stages
      of B, T, and NK cell lineage differentiation. In contrast to the GFP(-) cohort,
      there was minimal myeloid or erythroid potential in cells with an active RAG1
      locus. Partial overlap with TdT(+) cells suggested that distinctive early
      lymphocyte characteristics are not synchronously acquired. Rearrangement of Ig
      genes initiates before typical lymphoid lineage patterns of gene expression are
      established, and activation of the RAG1 locus transiently occurs in a large
      fraction of cells destined to become NK cells. These early lymphocyte progenitors
      (ELP) are distinct from stem cells, previously described prolymphocytes, or
      progenitors corresponding to other blood cell lineages.

PMID- 12196285
TI  - Rare, structurally homologous self-peptides promote thymocyte positive selection.
AB  - Although it is clear that positive selection of T cells involves recognition of
      specific self-peptide/MHC complexes, the nature of these self-ligands and their
      relationship to the cognate antigen are controversial. Here we used two
      complementary strategies to identify naturally occurring self-peptides able to
      induce positive selection of T cells bearing a specific T cell receptor, OT-I.
      Both the bioassay- and bioinformatics-based strategies identified the same self
      peptides, derived from F-actin capping protein and beta-catenin. These peptides
      displayed charge conservation at two key TCR contact residues. The biological
      activity of 43 other self-peptides and of complex peptide libraries directly
      correlated to the extent of conservation at TCR contact residues. These results
      demonstrate that selecting self-peptides are rare and can be identified by
      homology-based search strategies.

PMID- 12196286
TI  - Critical role of complement and viral evasion of complement in acute, persistent,
      and latent gamma-herpesvirus infection.
AB  - Several gamma-herpesviruses encode homologs of host regulators of complement
      activation (RCA) proteins, suggesting that they have evolved immune evasion
      strategies targeting complement. We evaluated the role of complement factor C3
      (C3) and the murine gamma-herpesvirus 68 (gammaHV68) RCA protein in viral
      pathogenesis. Deletion of the gammaHV68 RCA protein decreased virulence during
      acute CNS infection, and this attenuation was specifically reversed by deletion
      of host C3. The gammaHV68 RCA protein was also important for persistent viral
      replication and virulence in IFNgammaR(-/-) mice. In addition, C3 played a role
      in regulating latency, but this was not counteracted by the gammaHV68 RCA
      protein. We conclude that complement is a key host defense against gamma
      herpesvirus infection and that gamma-herpesviruses have evolved an immune evasion
      strategy that is effective against complement-mediated antiviral responses during
      acute but not latent infection.

PMID- 12196287
TI  - Wiskott-Aldrich syndrome protein regulates lipid raft dynamics during
      immunological synapse formation.
AB  - Immunological synapse assembly relies on the clustering of lipid rafts and is
      required for optimal T cell activation. We demonstrate that the Wiskott-Aldrich
      syndrome protein (WASP) is recruited to lipid rafts immediately after TCR and
      CD28 triggering and is required for the movements of lipid rafts. T cells from
      Wiskott-Aldrich syndrome (WAS) patients, lacking WASP, proliferate poorly after
      TCR/CD28 activation and have impaired capacities to cluster the lipid raft marker
      GM1 and to upregulate GM1 cell surface expression. T cell proliferation and lipid
      raft clustering are restored by retroviral transfer of the WASP gene. These
      results demonstrate that WASP plays a central role in the movements of lipid
      rafts and identify a potential mechanism underlying the T cell defect affecting
      WAS patients.

PMID- 12196288
TI  - CD4 regulatory T cells prevent lethal autoimmunity in IL-2Rbeta-deficient mice.
      Implications for the nonredundant function of IL-2.
AB  - Lethal autoimmunity associated with IL-2Rbeta-deficient mice is prevented after
      thymic transgenic expression of wild-type IL-2Rbeta in IL-2Rbeta(-/-) mice (Tg -/
      mice). Here, we show that CD4(+)CD25(+) regulatory T cells were not readily
      detected in IL-2Rbeta(-/-) mice, but the production of functional CD4(+)CD25(+) T
      cells was reconstituted in Tg -/- mice. Adoptive transfer of normal CD4(+)CD25(+)
      T cells into neonatal IL-2Rbeta-deficient mice prevented this lethal autoimmune
      syndrome. The CD4(+)CD25(+) T cells in disease-free adult IL-2Rbeta-deficient
      recipient mice were present at a near normal frequency, were solely donor
      derived, and depended on IL-2 for expansion. These observations indicate that the
      essential function of the IL-2/IL-2R system primarily lies at the level of the
      production of CD4(+)CD25(+) regulatory T cells.

PMID- 12196289
TI  - CDK inhibitor p18(INK4c) is required for the generation of functional plasma
      cells.
AB  - B cell terminal differentiation is associated with the onset of high-level
      antibody secretion and cell cycle arrest. Here the cyclin-dependent kinase (CDK)
      inhibitor p18(INK4c) is shown to be required within B cells for both terminating
      cell proliferation and differentiation of functional plasma cells. In its
      absence, B cells hyperproliferate in germinal centers and extrafollicular foci in
      response to T-dependent antigens but serum antibody titers are severely reduced,
      despite unimpaired germinal center formation, class switch recombination,
      variable region-directed hypermutation, and differentiation to antibody
      containing plasmacytoid cells. The novel link between cell cycle control and
      plasma cell differentiation may, at least in part, relate to p18(INK4c)
      inhibition of CDK6. Cell cycle arrest mediated by p18(INK4C) is therefore
      requisite for the generation of functional plasma cells.

PMID- 12196290
TI  - Rapid expansion and IL-4 expression by Leishmania-specific naive helper T cells
      in vivo.
AB  - CD4 T cells are pivotal for effective immunity, yet their initial differentiation
      into effector subsets after infection remains poorly defined. We examined CD4 T
      cells specific for the immunodominant Leishmania major LACK antigen using
      MHC/peptide tetramers and IL-4 reporter mice. Comprising approximately 15
      cells/lymph node in naive mice, LACK-specific T cells expanded over 100-fold, and
      70% acquired IL-4 expression by 96 hr. Despite their pathogenic role in
      susceptible mice, LACK-specific precursor frequency, expansion, and IL-4
      expression were comparable between susceptible and resistant mice. When injected
      with unrelated antigen, Leishmania efficiently activated IL-4 expression from
      naive antigen-specific T cells. CD4 subset polarization in this highly
      characterized model occurs independently from IL-4 expression by naive T cells,
      which is activated indiscriminately after parasitism.

PMID- 12196291
TI  - The interaction properties of costimulatory molecules revisited.
AB  - B7-1 and B7-2 are generally thought to have comparable structures and affinities
      for their receptors, CD28 and CTLA-4, each of which is assumed to be bivalent. We
      show instead (1) that B7-2 binds the two receptors more weakly than B7-1, (2)
      that, relative to its CTLA-4 binding affinity, B7-2 binds CD28 2- to 3-fold more
      effectively than B7-1, (3) that, unlike B7-1, B7-2 does not self-associate, and
      (4) that, in contrast to CTLA-4 homodimers, which are bivalent, CD28 homodimers
      are monovalent. Our results indicate that B7-1 markedly favors CTLA-4 over CD28
      engagement, whereas B7-2 exhibits much less bias. We propose that the distinct
      structures and binding properties of B7-1 and B7-2 account for their overlapping
      but distinct effects on T cell responses.

PMID- 12196292
TI  - In vivo depletion of CD11c+ dendritic cells abrogates priming of CD8+ T cells by
      exogenous cell-associated antigens.
AB  - Cytotoxic T lymphocytes (CTL) respond to antigenic peptides presented on MHC
      class I molecules. On most cells, these peptides are exclusively of endogenous,
      cytosolic origin. Bone marrow-derived antigen-presenting cells, however, harbor a
      unique pathway for MHC I presentation of exogenous antigens. This mechanism
      permits cross-presentation of pathogen-infected cells and the priming of CTL
      responses against intracellular microbial infections. Here, we report a novel
      diphtheria toxin-based system that allows the inducible, short-term ablation of
      dendritic cells (DC) in vivo. We show that in vivo DC are required to cross-prime
      CTL precursors. Our results thus define a unique in vivo role of DC, i.e., the
      sensitization of the immune system for cell-associated antigens. DC-depleted mice
      fail to mount CTL responses to infection with the intracellular bacterium
      Listeria monocytogenes and the rodent malaria parasite Plasmodium yoelii.

PMID- 12196293
TI  - Herpesviral protein targets a cellular WD repeat endosomal protein to
      downregulate T lymphocyte receptor expression.
AB  - Herpesvirus saimiri Tip associates with Lck and downregulates Lck signal
      transduction. Here we demonstrate that Tip targets a lysosomal protein p80, which
      consists of an N-terminal WD repeat domain and a C-terminal coiled-coil domain.
      Interaction of Tip with p80 facilitated lysosomal vesicle formation and
      subsequent recruitment of Lck into the lysosomes for degradation. Consequently,
      Tip interactions with Lck and p80 result in downregulation of T cell receptor
      (TCR) and CD4 surface expression. Remarkably, these actions of Tip are
      functionally and genetically separable: the N-terminal p80 interaction is
      responsible for TCR downregulation and the C-terminal Lck interaction is
      responsible for CD4 downregulation. Thus, lymphotropic herpesvirus has evolved an
      elaborate mechanism to deregulate lymphocyte receptor expression to disarm host
      immune control.

PMID- 12196294
TI  - [Chlamydia pneumoniae and acute respiratory tract infections in breast-feeding
      infants: simultaneous mother-child serological study in Niamey (Niger)].
AB  - The age and the origin of Chlamydia pneumoniae primary infection in Sahelian
      areas are unknown. To evaluate the prevalence of C. pneumoniae antibodies, the
      authors studied the serological status of C. pneumoniae-, C. psittaci- and C.
      trachomatis-specific antibodies of 50 mother-child couples using the
      microimmunofluorescence technique. Children were 10 to 34 month-old (18,1   6,2,
      mean   SD), breast-fed and hospitalized with acute respiratory tract infections
      in Niamey (republic of Niger). Specific C. pneumoniae IgG antibodies were present
      in 46/48 (95.8%) children, IgA in 32/48 (66.6%). In the mothers, specific C.
      pneumoniae IgG antibodies were present in 40/48 (83.3%), IgA in 31/48 (64.6%).
      The specific IgM antibodies were steadily absent in mothers and children. In the
      mother-child couples, 38/46 (79.2%) had specific C. pneumoniae IgG antibodies and
      23/47 (48.9%) had IgA. The prevalence of specific C. pneumoniae IgG and IgA
      antibodies is very high in this population. These results point out that C.
      pneumoniae primary infection is very precocious in this paediatric population and
      is very different from American, Asian and European reports. A mother-child
      direct contamination during the first months of life in this breast-feeding
      pediatric population is discussed.

PMID- 12196295
TI  - [Oral health in school children in Lebanon].
AB  - This survey is the first epidemiological investigation to be carried out at the
      national level in Lebanon. It provides a first series of basic data indicative of
      the present oral health situation in the country. The results of this survey
      should contribute to the elaboration of a National Oral Health Plan and to the
      development of a broad strategy for the implementation of preventive measures
      [8]. Indeed, experience clearly indicates that dental caries cannot be
      successfully eradicated nation-wide through curative measures only and that
      preventive measures must also be implemented. The main effort in the field of
      oral health care should mainly focus on health promotion and education, leading
      in turn to improved oral hygiene.

PMID- 12196296
TI  - [The impact of chemotherapy on haematological and biochemical profiles during
      malignant blood diseases in Abidjan, Cote d'Ivoire].
AB  - Our research concerned the impact of chemotherapy on the haematological and
      biochemical profiles of patients diagnosed with malignant blood diseases and
      receiving treatment in Abidjan. The study covered 57 patients, 26 of whom were
      receiving treatment. Burkitt's lymphoma was the most common type of malignant
      blood disease encountered (33%). The proportion of men was slightly higher, at
      54%, and the average age of patients was 26. Hyperleucocytosis, anaemia and
      medullar blastosis were the most common blood disorders. The tumours arising from
      hyperleucocytosis and medullar blastosis caused increases in proteins from
      inflammatory reaction. The increase was moderate for alpha 1 globulins and
      haptoglobin and high (at least twice the reference levels) for C Reactive Protein
      (CRP) and orosomucoid. Full remission was only achieved in the cases of Burkitt's
      lymphoma, in which the haematological and biochemical parameters reached near
      normal levels following treatment. In cases of chronic myeloid leukaemia the
      treatment lowered the hyperleucocytosis but the high rate of CRP might indicate
      that the disease was reaching a more acute phase. In the cases of acute
      leukaemia, chemotherapy did not achieve full remission: the alpha 1 globulins,
      including orosomucoids, were the most sensitive proteins to treatment. Even
      though the rate of CRP was lowered, it remained high in all cases of acute
      leukaemia. Neither haematological nor biochemical data proved superior to the
      other in monitoring the effectiveness of the treatment or the gradual return of
      the disease. It would be beneficial to combine them in order to obtain a clearer
      assessment of the effectiveness of chemotherapy.

PMID- 12196299
TI  - [Determining the optimal fluorine dose in the drinking water of the South Center
      hydrological region of Haiti].
AB  - This study aims at determining the optimal dose of fluorine in the drinking water
      in the South Center region of Haiti. This region has an average daily temperature
      ranging from 17 to 33  C. Water samples were collected from November 15th to
      December 20th 2000 on the water resource of some of the counties of the
      hydrological South Center region of Haiti. The results show that the
      concentration of fluorine in this region varies between 0 and 0.83 mg/litre.
      However, the calculated optimal dose based on the temperature measured show that
      fluorine concentration of water should be between 0.7 and 1 mg/litre.

PMID- 12196297
TI  - [Quality of disease management of sexually transmitted diseases: investigation of
      care in six countries in West Africa].
AB  - OBJECTIVES: the objectives of this study were, in healthcare facilities in six
      countries in West Africa, to: (1) estimate the proportion of patients consulting
      for sexually transmitted diseases (STDs) for whom an adequate case history was
      taken and who received an appropriate physical examination and effective
      treatement (prevention indicator PI6); (2) to determine the percentage of
      patients who were given advice on condom use and notification of sexual partners
      for STD treatment (prevention indicator PI7); (3) to determine the level of
      knowledge of healthcare workers concerning STD case management; and (4) to
      compare reported and observed behaviour regarding STD case management by
      healthcare workers. MATERIAL AND METHOD: this descriptive study was carried out
      in 240 health care facilities in six countries: Benin, Burkina Faso, Cote
      d'Ivoire, Guinea, Mali, and Senegal, using the WHO protocol for PI6 and PI7
      indicators to evaluate the quality of management of urethral discharge and
      genital ulcers, as well as an extension of this protocol to evaluate STD
      syndromes specific to women, namely vaginal discharge and pelvic inflammatory
      disease. Healthcare workers were observed during STD consultations, and
      thereafter interviewed. Up to five observations per healthcare worker were
      carried out over a period of three days spent at each health care facility.
      Criteria for an adequate case history were inclusion of questions on the nature,
      time of initiation and duration of symptoms, and for physical examination,
      visualisation and examination of genital organs for discharge and lesions.
      Treatments prescribed were judged as effective when in conformity with national
      algorithms for syndromic STD management. The PI6 indicator was estimated as the
      proportion of cases where an adequate case history was taken, an appropriate
      physical examination carried out and effective treatment prescribed. The PI7
      score corresponded to the percentage of patients who received advice on condom
      use and partner notification for treatment. In order to control for intra
      healthcare-worker correlation, the SUUDAN software was used for the computation
      of 95% confidence intervals of the proportions, obtained from univariate analysis
      in EPI-INFO, and for the comparison of the PI6 and PI7 scores by country, sex,
      marital status and symptoms of the patient, as well as by level of qualification
      of the healthcare workers, using the khi2 test. RESULTS: overall, 613
      observations and 504 interviews of 263 healthcare workers were carried out. The
      majority of STD patients were female (57.1%) and unmarried (53.0%). Healthcare
      workers were most frequently doctors (33.6%) and the most common complaint was
      vaginal discharge (42.2%). Intercountry variation was observed for all these
      variables. An adequate case history was taken in 84.6% of cases and an adequate
      physical examination carried out in 60.8% of cases. Healthcare workers gave a
      diagnosis in conformity with national syndromic STD management algorithms in
      35.3% of cases, while effective treatment was given to 14.1% of patients.
      Patients were encouraged to use condoms in 19.5% of cases and to advise their
      partners to seek treatment in 50.8% of cases; this advice was given more
      frequently to men than to women. PI6 and PI7 scores were respectively 9.9% (95%
      CI: 6.9%; 12.9%) and 15.4% (95% CI: 11.4%; 19.2%). Healthcare workers' knowledge
      of effective STD treatment regimes was low. Practices reported during interviews
      with regard to STD patients were comparable to observed behaviour with regard to
      case history-taking and physical examination, but not for diagnosis and treatment
      nor for condom promotion or partner notification advice. CONCLUSION: the results
      of this study demonstrate the low quality of STD management in the six countries
      evaluated, which may be explained by the lack of availability of examination
      material, the inadequate knowledge of healthcare workers, as well as the
      infrequent promotion of STD prevention methods, particularly in women.

PMID- 12196300
TI  - [Analysis of data routinely collected in the maternity ward of Rutshuru in the
      Democratic Republic of the Congo between 1980 and 1998. I. Maternal mortality and
      obstetrical interventions].
AB  - This report is the first of 2 papers that analyse data routinely collected in the
      maternity ward of Rutshuru (democratic Republic of Congo). The present work
      describes the evolution of caesarean section, maternal deaths and the associated
      risk factors. MATERIAL AND METHODOLOGY: Between 1980 and 1998, data on 13,042
      deliveries were collected. Characteristics, mortality, morbidity of mothers and
      new-borns and obstetrical interventions were recorded. The statistical analyses
      applied included khi2, t-test, simple linear and multiple logistic regression.
      RESULTS: Fifteen percent had a caesarean section and 1.9% of women died. When
      referred to the expected births during the period, these numbers led to a ratio
      of 150 maternal deaths for 100,000 expected births and a ratio of caesarean
      section of 1.2%. At admission, 35% of the women presented at least one of the
      four risk factors used for reference. The proportion of women with at least one
      of the 4 risk factors went up from 26.1% to 39.5%. The proportion of caesarean
      sections went up from 1.9% to 34.1%. The proportion of maternal deaths remained
      constant except in 1988, 1994, 1995 and 1997. Three of the four reference
      factors, the Baudeloque diameter, parity and height were associated with
      caesarean section. Age only was associated with maternal death. Education and
      marital status were both associated with caesarean section and maternal death.
      CONCLUSION: This analysis shows high levels of maternal mortality and caesarean
      section. The authors recommend to analyse on a larger scale the value of the
      reference factors used in antenatal services and to standardise indications for
      the different obstetrical interventions.

PMID- 12196301
TI  - [Analysis of data routinely collected in the maternity ward of Rutshuru in the
      Democratic Republic of the Congo between 1980 and 1998. II. New-born deaths and
      low birth weights].
AB  - This second paper aims at deriving useful information allowing to improve the
      strategy applied for maternal health care. MATERIAL AND METHODOLOGY: Between 1980
      and 1998, data on 13,042 deliveries were collected. Characteristics, mortality,
      morbidity of mothers and new-born and obstetrical interventions were recorded.
      The present work describes the evolution of low birth weight (LBW), new-born
      deaths, and associated risk factors. The statistical analyses applied included
      khi2, t-test, and multiple logistic regression. RESULTS: Eighteen percent of new
      born weights below 2.5 kg and 7.9% died. The proportion of low birth weights
      remains globally constant. Low proportions of new-born deaths were observed in
      1981, 1982, 1988 and 1998. At admission, 35% of the women presented at least one
      of the four risks defined by the factors used for reference; this proportion went
      up from 26.1 to 39.2%. The four reference factors were associated with low birth
      weight. Baudelocque diameter and age were not associated with new-born death.
      Education and BMI were associated with an increased risk of new-born death.
      Marital status was not associated with any of the two outcomes. CONCLUSION: This
      analysis shows small variation of LBWs and perinatal deaths. It confirms the
      association between these two outcomes and most of the risk factors studied. The
      efficacy of the strategies implemented for improving perinatal health is
      questioned. The authors recommend that they be reassessed.

PMID- 12196302
TI  - [Hospital staff use of generic essential drugs: the case of Yalgado Ouedraogo
      University Hospital Centre (Burkina Faso)].
AB  - With the institution of the primary health care strategy in 1978 and the
      devaluation of the CFA franc in 1994 the French-speaking countries of Africa are
      striving to encourage the prescription of generic essential drugs. However, their
      prescription rates continue to remain low in these countries, especially in the
      major hospitals. The aim of this study was thus to determine how prescribers at
      the national hospital in Ouagadougou were informed about genetric drugs and to
      analyse their attitudes and practices with a view to elucidating the barriers to
      a more widespread use of generic essential drugs in hospital practice. The study
      consisted of a survey of all of the qualified prescribers (n=194) at Yalgado
      Ouedraogo University Hospital Centre in 1998. Thirty refused to participate and
      35 questionnaires were discarded because they were poorly filled out. So, the
      responses of 129 (66.5%) prescribers in all were analysed. More than 80%
      (106/129) of the prescribers were aware of the existence of generic drugs in the
      hospital, but only 24.8% of them considered generics to have the same efficacy as
      their corresponding proprietary drugs. However, 64.3% of the prescribers felt
      that there was a place for generic drugs in a last-resort echelon of medical
      care, such as the national hospital in Ouagadougou, and 85.3 % were willing to
      prescribe them for their patients because of their low cost. The analysis of the
      data and the responses to the open questions show that the main conditions that
      would boost the prescription of generic essential drugs by hospital staff are as
      follows: generic essential drugs available in appropriate dosage forms and of
      guaranteed quality; appropriate basic training starting in medical and nursing
      schools; providing the prescribers with information and further education about
      generic drugs; and better dispensing of these drugs by the hospital's central
      pharmacy.

PMID- 12196303
TI  - [The sleep of Africans and Europeans in the Ivory Coast: questionnaire study].
AB  - Sleep behaviour has been extensively studied with questionnaires in
      industrialised countries to investigate the epidemiology of sleep-wake disorders.
      However, only few attempts have yet been made to examine sleep behaviour of
      people living in Africa. Although, a large number of studies in hot or cold
      environments have used short-term exposures, reporting disrupted sleep for most
      of them, long-term exposures to stressful thermal environments are rare in the
      literature. Prior to the present investigation, we used questionnaires to analyse
      the effects of seasonal heat increase on perceived sleep behaviour and sleep
      quality in young native African students in Niger [7], even though these methods
      of investigation are by no means as accurate as polysomnographic recordings. The
      hypothesis was that sleep behaviour may be influenced by climatic variations in a
      hot dry tropical climate. Such climatic variations have been shown to induce
      seasonal heat acclimatisation marked by changes in body temperature rhythms in
      the hot versus the cool season [13]. Sleep behaviour was examined during two 7
      day periods in January ("cool-dry" season, 88 subjects) and May ("hot-dry"
      season, 53 subjects). The questionnaire was completed after night sleep and/or
      naps. The subjects slept an average of 7 1/2 hours a day, most of them having
      afternoon naps. They experienced no major seasonal variation in their sleep
      behaviour, but for an increased number of awakenings during the hot season.
      Restorative quality of sleep scored lower after a nap than after nocturnal sleep.
      Therefore, general sleep characteristics were not modified by seasonal
      temperature variations in African native students, perhaps because of the limited
      changes in daylight under the low latitude of Niamey. Another investigation was
      carried out using the same 12-item questionnaire in Abidjan on 78 medical
      students who did not have a nap [9]. Contrary to the Niamey students, the Abidjan
      subjects adopted short duration sleep schedules, without any effect on the
      subjective quality of the restorative properties of their sleep.

PMID- 12196304
TI  - [Ectopic pregnancy in Senegal].
AB  - The objective of this prospective study was to analyse the epidemiology and
      prognosis of ectopic pregnancy in Senegal. From January 1 to December 31, 1996,
      255 ectopic pregnancies were registered. The national rate of ectopic pregnancy
      was 0.6%. of expected pregnancies. However, rates differed greatly between areas
      in Senegal, with extremes ranging from 0.85%. in Dakar to 0.32%. in Thies. The
      epidemiological profile was that of a young woman-mean age: 23 years old, mean
      parity=3, admitted with broken ectopic pregnancy (95%). A salpingectomy was
      performed in all cases. The maternal mortality rate was 1.20%, while morbidity,
      mainly due to post-operative infection, was found in 2.7% of the cases.

PMID- 12196305
TI  - [How to search National Library of Medicine databases. NLM Gateway: [presentation
      and method of use (update: May 15, 2002)].
AB  - The aim of this paper is to provide a practical kit in French for bibliographic
      retrieval using NLM Gateway, a Web-based retrieval service that lets users search
      simultaneously in multiple National Library of Medicine databases and information
      resources. We try to explain screen by screen, how this bibliographic retrieval
      tool works and try to make it easy to use to every single French-speaking end
      user.

PMID- 12196306
TI  - [Leprosy in Haiti].
AB  - Leprosy has yet a great impact on public health in Haiti. A study was carried out
      in Haiti from 1977 to 1999. On 2,160 registered cases, mostly are
      paucibacillaries: 412 cases are under 15 year old patients and 1,306 more than 15
      year old. Multibacillaries cases are 85 in under 15 year old patients and 357 in
      more than 15 year old. By the improvement of sanitary conditions, detecting cases
      and multidrug therapy, leprosy had decreased during these last years, with an
      incidence from 0.1 to 0.2%. However, with the increasing poverty and political
      disorders, the control of leprosy remains difficult in Haiti.

PMID- 12196307
TI  - In nonrandomized studies, can we use a person's preimmunization experience to
      help gauge the safety and efficacy of immunization?

PMID- 12196308
TI  - Epidemiology and survival analysis of cystic fibrosis in an area of intense
      neonatal screening over 30 years.
AB  - This population-based study was conducted in Veneto and Trentino (northwestern
      Italy, population 5 million). In this area, neonatal screening for cystic
      fibrosis started in 1973 and has been virtually universal since the early 1980s.
      During this study, the estimated incidence of cystic fibrosis in this region was
      1/2,650 livebirths per year. The authors analyzed data on 593 patients born in
      1938-2000 and living in the region who were followed by a single referral center.
      Median time from birth to confirmation of diagnosis after screening was 32 days
      (range, 0-1,531). For patients whose disease was recognized after symptoms
      occurred, median age at diagnosis was always less than 1 year. Median survival
      age was 37.7 years. Long-term survival (to age 20-30 years) was not significantly
      influenced by mode of diagnosis (screened or unscreened), sex, or age at
      diagnosis for unscreened patients (<1, 1-5, >5 years). Current survival analysis
      of three consecutive decades showed that improving survival tended to vanish in
      the last years of the study. The authors concluded that a regional neonatal
      screening program allows very early recognition of cystic fibrosis. They could
      not conclude that neonatal screening improves long-term survival if compared with
      diagnosis by symptoms in early infancy.

PMID- 12196309
TI  - Physical activity and menstrual cycle characteristics in two prospective cohorts.
AB  - Relations between physical activity and prospectively collected menstrual cycle
      characteristics were examined in two large cohorts. One cohort consisted of women
      employed in the semiconductor industry in 1989 who participated in a prospective
      study of reproductive outcomes (n = 367). The other consisted of women living in
      Tecumseh, Michigan, who completed both the 1992-1993 and 1993-1994 examinations
      for the Michigan Bone Health Study (n = 328). Mean cycle length, variability of
      cycle length, and mean bleed length were calculated from daily diaries
      (Semiconductor cohort) or monthly menstrual calendars (Michigan cohort) for a
      median of five and 11 cycles, respectively. Physical activity was assessed by
      self-report at baseline and expressed as metabolic equivalent-minutes per week.
      In the Semiconductor study, women also reported daily minutes of vigorous
      exercise in their diaries. In the Michigan cohort, total physical activity, total
      recreational physical activity, and vigorous recreational activity were
      positively associated with cycle length. The magnitude of these associations
      declined as body mass index increased. In the Semiconductor cohort, the minutes
      of daily vigorous exercise were positively associated with cycle length only in a
      repeated-measures analysis. These findings lend modest support to the hypothesis
      that moderate levels of physical activity can lengthen the menstrual cycle.

PMID- 12196310
TI  - Natural history of bone loss over 6 years among premenopausal and early
      postmenopausal women.
AB  - The aims of this prospective cohort study were to determine rates of
      premenopausal and early postmenopausal bone loss, age at onset of bone loss, and
      whether rates of bone loss depend on baseline bone mineral density (BMD). The
      cohort of 614 women aged 24-44 years at baseline from the longitudinal Michigan
      Bone Health Study was followed for 6 years beginning in 1992-1993. Up to five BMD
      measurements of the lumbar spine (L(2-4)) and the femoral neck were obtained
      through 1998-1999 by using dual x-ray absorptiometry and were standardized (as z
      scores) relative to a young adult, female BMD distribution. Regression models
      were used to estimate rates of BMD change and to examine BMD as a function of
      age. At the lumbar spine, the rate of BMD change for premenopausal women varied
      with time. At the femoral neck, the rate of change was -1.6% (95% confidence
      interval: -0.9%, -2.3%) of a z score annually (annual loss of 0.3% of baseline
      BMD (g/cm(2))). Evidence for age at onset of bone loss at the lumbar spine was
      inconclusive. Bone loss began by the midtwenties at the femoral neck. Additional
      annual change of -0.7% (95% confidence interval: -0.2%, -1.2%) of a z score was
      observed at the femoral neck for each unit increase in BMD z score at baseline.

PMID- 12196311
TI  - Correlates of forearm bone mineral density in young Norwegian women: the Nord
      Trondelag Health Study.
AB  - Maximizing attainment of optimal peak bone mineral density (BMD) is a potential
      osteoporosis prevention strategy. The main objective of this study was to
      identify correlates of forearm BMD in young adult women. Population-based data
      derived from standardized questionnaires administered to healthy women aged 19-35
      years in Nord-Trondelag, Norway (n = 963), were collected in 1995-1997. Forearm
      BMD was assessed by single x-ray absorptiometry. Multiple linear and logistic
      regression analyses were used to determine correlates of BMD (g/cm(2)) and lowest
      quintile of BMD, respectively, at the ultradistal and distal sites. The mean age
      and weight of the cohort were 29.7 years (standard deviation 4.7) and 68.6 kg
      (standard deviation 12.5), respectively. Age and weight were positively
      associated with BMD at both forearm sites. When data were controlled for age and
      weight, later age at menarche and lack of milk consumption were associated with
      lower BMD values. In both linear models and logistic models, none of the factors
      vitamin D intake, physical activity, smoking, alcohol consumption, amenorrhea,
      oral contraceptive use, number of pregnancies, history of breastfeeding, and
      family history of osteoporosis were found to be significantly associated with
      BMD. Prior studies have suggested that calcium supplementation in children is
      useful for optimizing peak BMD. Further studies exploring the relation between
      lifestyle factors and BMD are warranted to search for ways to maximize attainment
      of peak BMD.

PMID- 12196312
TI  - Pregnancy hormone metabolite patterns, pregnancy symptoms, and coffee
      consumption.
AB  - Because of contradictory reports of pregnancy outcomes and coffee intake, this
      study was designed to determine how hormone metabolite levels, symptoms, and
      coffee consumption patterns are related. Eligible subjects were recruited in
      Cincinnati, Ohio, from 1996 to 1998, aged 18-40 years, and nonsmokers; drank at
      least 18 ounces (1 ounce = 29.6 ml) of coffee per week (including decaffeinated)
      at the last menstrual period; and were enrolled by 9 weeks from the last
      menstrual period. Beverage consumption and pregnancy symptoms were recorded
      daily. Weekly, first-morning urine samples were collected to assess human
      chorionic gonadotropin, estrone-3-glucuronide, and pregnanediol-3-glucuronide. A
      time-dependent, repeated measures analysis was performed to test several
      associations. Data from 92 subjects were analyzed with the following results. 1)
      Coffee consumption was significantly, inversely associated with weekly levels of
      estrone-3-glucuronide and human chorionic gonadotropin. 2) Weekly hours of nausea
      were significantly, directly associated with human chorionic gonadotropin and
      inversely with estrone-3-glucuronide and pregnanediol-3-glucuronide. 3) Weekly
      coffee consumption was significantly associated with vomiting but not with nausea
      or appetite loss. 4) Weekly levels of pregnanediol-3-glucuronide were 32.2% lower
      in subjects who drank at least 8 ounces of coffee/day at the last menstrual
      period, though above what was necessary to maintain those pregnancies. This study
      shows the significance of these important variables to be considered in future
      research.

PMID- 12196313
TI  - Carotid wall thickness and years since bilateral oophorectomy: the Los Angeles
      Atherosclerosis Study.
AB  - Evidence that coronary heart disease risk increases with surgical menopause is
      consistent. However, findings concerning atherosclerosis and surgical menopause
      are inconsistent. The Los Angeles Atherosclerosis Study (1995-1996) assessed the
      cross-sectional relation at baseline between years since bilateral oophorectomy
      and common carotid artery intima-media thickness (IMT). Participants included 269
      employed California women asymptomatic for cardiovascular disease and aged 45-60
      years. Ninety-seven women reported a hysterectomy: 42 without oophorectomy or a
      unilateral oophorectomy and 55 with a concurrent bilateral oophorectomy. IMT was
      measured bilaterally with B-mode ultrasound and was regressed on age, height, and
      years since hysterectomy in each group. Among women who had undergone bilateral
      oophorectomy, IMT was significantly related to years since hysterectomy (beta =
      0.042 (standard error, 0.018) mm/10 years, p = 0.02). However, IMT was unrelated
      to years since hysterectomy in the no bilateral oophorectomy group (beta = 0.005
      (standard error, 0.023) mm/10 years, p = 0.82). Adjustment for high density
      lipoprotein or low density lipoprotein cholesterol attenuated the association
      between IMT and years since hysterectomy by about a fourth in the bilateral
      oophorectomy group. Since over 90% of this group had a history of hormone
      replacement therapy use, the finding that years since bilateral oophorectomy was
      associated with increasing atherosclerosis conflicts with a well-known finding
      that such therapy reverses the adverse effect of bilateral oophorectomy on
      coronary heart disease.

PMID- 12196314
TI  - Risk factors for Alzheimer's disease: a prospective analysis from the Canadian
      Study of Health and Aging.
AB  - A prospective analysis of risk factors for Alzheimer's disease was a major
      objective of the Canadian Study of Health and Aging, a nationwide, population
      based study. Of 6,434 eligible subjects aged 65 years or older in 1991, 4,615
      were alive in 1996 and participated in the follow-up study. All participants were
      cognitively normal in 1991 when they completed a risk factor questionnaire. Their
      cognitive status was reassessed 5 years later by using a similar two-phase
      procedure, including a screening interview, followed by a clinical examination
      when indicated. The analysis included 194 Alzheimer's disease cases and 3,894
      cognitively normal controls. Increasing age, fewer years of education, and the
      apolipoprotein E epsilon4 allele were significantly associated with increased
      risk of Alzheimer's disease. Use of nonsteroidal anti-inflammatory drugs, wine
      consumption, coffee consumption, and regular physical activity were associated
      with a reduced risk of Alzheimer's disease. No statistically significant
      association was found for family history of dementia, sex, history of depression,
      estrogen replacement therapy, head trauma, antiperspirant or antacid use,
      smoking, high blood pressure, heart disease, or stroke. The protective
      associations warrant further study. In particular, regular physical activity
      could be an important component of a preventive strategy against Alzheimer's
      disease and many other conditions.

PMID- 12196315
TI  - Wine drinking and risk of non-Hodgkin's lymphoma among men in the United States:
      a population-based case-control study.
AB  - The relation between wine consumption and non-Hodgkin's lymphoma (NHL) was
      investigated using data from the Selected Cancers Study. Cases (n = 960) were men
      aged 32-60 years diagnosed with NHL from 1984 to 1988 and identified from eight
      US population-based cancer registries. Controls (n = 1,717) were men recruited by
      random digit dialing and frequency matched to cases by age and registry. Logistic
      regression was used to calculate odds ratios and 95% confidence intervals
      adjusted for age, registry, race/ethnicity, education, and smoking. Odds ratios
      for men who consumed less than one and those who consumed one or more wine drinks
      per day were 0.8 (95% confidence interval: 0.5, 1.3) and 0.4 (95% confidence
      interval: 0.2, 0.9) compared with nondrinkers, respectively (p for trend = 0.02).
      Among wine drinkers who consumed alcohol beverages from ages 16 years or less,
      odds ratios for intakes of less than one and one or more wine drinks per day were
      0.4 (95% confidence interval: 0.2, 0.97) and 0.3 (95% confidence interval: 0.1,
      0.8), respectively (p for trend = 0.004). No associations were evident for beer
      or spirits. These data show that consumption of wine, but not of beer or spirits,
      is associated with a reduced NHL risk.

PMID- 12196316
TI  - Effect heterogeneity by a matching covariate in matched case-control studies: a
      method for graphs-based representation.
AB  - The authors describe a method for assessing and characterizing effect
      heterogeneity related to a matching covariate in case-control studies, using an
      example from veterinary medicine. Data are from a case-control study conducted in
      Texas during 1997-1998 of 498 pairs of horses with colic and their controls.
      Horses were matched by veterinarian and by month of examination. The number of
      matched pairs of cases and controls varied by veterinarian. The authors
      demonstrate that there is effect heterogeneity related to this characteristic
      (i.e., cluster size of veterinarians) for the association of colic with certain
      covariates, using a moving average approach to conditional logistic regression
      and graphs-based methods. The method described in this report can be applied to
      examining effect heterogeneity (or effect modification) by any ordered
      categorical or continuous covariates for which cases have been matched with
      controls. The method described enables one to understand the pattern of variation
      across ordered categorical or continuous matching covariates and allows for any
      shape for this pattern. This method applies to effect modification when causality
      might be reasonably assumed.

PMID- 12196317
TI  - Geocoding and monitoring of US socioeconomic inequalities in mortality and cancer
      incidence: does the choice of area-based measure and geographic level matter?:
      the Public Health Disparities Geocoding Project.
AB  - Despite the promise of geocoding and use of area-based socioeconomic measures to
      overcome the paucity of socioeconomic data in US public health surveillance
      systems, no consensus exists as to which measures should be used or at which
      level of geography. The authors generated diverse single-variable and composite
      area-based socioeconomic measures at the census tract, block group, and zip code
      level for Massachusetts (1990 population: 6,016,425) and Rhode Island (1990
      population: 1,003,464) to investigate their associations with mortality rates
      (1989-1991: 156,366 resident deaths in Massachusetts and 27,291 in Rhode Island)
      and incidence of primary invasive cancer (1988-1992: 140,610 resident cases in
      Massachusetts; 1989-1992: 19,808 resident cases in Rhode Island). Analyses of all
      cause and cause-specific mortality rates and all-cause and site-specific cancer
      incidence rates indicated that: 1) block group and tract socioeconomic measures
      performed comparably within and across both states, but zip code measures for
      several outcomes detected no gradients or gradients contrary to those observed
      with tract and block group measures; 2) similar gradients were detected with
      categories generated by quintiles and by a priori categorical cutpoints; and 3)
      measures including data on economic poverty were most robust and detected
      gradients that were unobserved using measures of only education and wealth.

PMID- 12196318
TI  - Association of helmet use with death in motorcycle crashes: a matched-pair cohort
      study.
AB  - The association of helmet use with death in a motorcycle crash can be estimated
      using matched-pair cohort methods. By estimating effects among naturally matched
      pairs on the same motorcycle, one can account for potential confounding by
      motorcycle characteristics, crash characteristics, and other factors that may
      influence the outcome. The authors used Fatality Analysis Reporting System data,
      from 1980 through 1998, for motorcycles that crashed with two riders and either
      the driver or the passenger, or both, died. For their main analysis, the authors
      estimated the relative risk of death using conditional Poisson regression. The
      relative risk of death, accounting for the matching on motorcycle and adjusted
      for age, sex, and seat position, for a helmeted rider compared with an unhelmeted
      rider was 0.61 (95% confidence interval: 0.54, 0.70). The authors suggest that
      conditional Poisson regression is useful for the analysis of traffic crash data,
      where occupants are naturally matched in a vehicle and where crash-related
      confounders may be difficult or impossible to measure.

PMID- 12196320
TI  - Re: Does tea affect cardiovascular disease? A meta-analysis.

PMID- 12196322
TI  - Automated external defibrillator use by police responders: where do we go from
      here?

PMID- 12196323
TI  - Was your mother right--do we always need to close the door?

PMID- 12196324
TI  - Report of the Task Force on Research in Pediatric Cardiovascular Disease.

PMID- 12196325
TI  - Recommendations of the National Heart, Lung, and Blood Institute Heart and Lung
      Xenotransplantation Working Group.
AB  - The National Heart, Lung, and Blood Institute (NHLBI) recently convened the Heart
      and Lung Xenotransplantation Working Group to identify hurdles to the clinical
      application of xenotransplantation, defined as the use of animal organs or tissue
      for transplantation, and to recommend possible solutions to these problems. The
      group consisted of experts in xenotransplantation from academia, industry, and
      federal agencies, and the discussions focused on those areas within the mission
      of the NHLBI. The areas covered included immunologic and physiological barriers
      to xenotransplantation, the limitations of the current animal models, the need
      for collaboration among groups, the high costs of studies using nonhuman primates
      and genetic engineering of pigs, and the unique problems of lung
      xenotransplantation. This report is a summary of those discussions.

PMID- 12196326
TI  - Cardiology patient page. Fainting.

PMID- 12196327
TI  - Persistent infarct-related artery occlusion is associated with an increased
      myocardial apoptosis at postmortem examination in humans late after an acute
      myocardial infarction.
AB  - BACKGROUND: Myocardial apoptosis persists beyond the acute phases of acute
      myocardial infarction (AMI) and is associated with left ventricular (LV)
      remodeling. Infarct-related artery (IRA) patency is considered a favorable
      prognostic factor after AMI and may be associated with more favorable LV
      remodeling because of reduced apoptosis at the site of AMI. The aim of this study
      was to assess the influence of IRA status on apoptotic rate (AR) in the hearts of
      subjects dying late after AMI. METHODS AND RESULTS: We used colocalization for in
      situ end-labeling of DNA fragmentation and immunohistochemistry for caspase-3 to
      calculate the AR at time of death (12 to 62 days after AMI) in 16 hearts with
      persistently occluded IRAs and in 8 hearts with patent IRAs. No significant
      differences were found when comparing the clinical characteristics of the 2
      groups. Occluded IRA was associated with significantly higher AR at site of
      infarction (25.8% [interquartile range 20.9% to 28.5%] versus 2.3% [interquartile
      range 0.6% to 5.0%], P<0.001). This strong correlation between IRA occlusion and
      AR remained statistically significant even after correction for clinical
      characteristics such as sex, age, history of previous additional AMI or heart
      failure, transmural AMI, anterior AMI, fibrinolytic treatment, time from AMI to
      death, trauma as cause of death, and multivessel coronary disease (P=0.003).
      CONCLUSIONS: A significantly higher AR was associated with persistent IRA
      occlusion late post-AMI. These data may suggest that the post-AMI benefits
      observed with a patent IRA (the "open-artery hypothesis") may in part be due to
      reduced myocardial apoptosis.

PMID- 12196328
TI  - Elevated plasma aldosterone levels despite complete inhibition of the vascular
      angiotensin-converting enzyme in chronic heart failure.
AB  - BACKGROUND: Plasma aldosterone levels are elevated in patients with chronic heart
      failure (CHF) taking angiotensin-converting enzyme (ACE) inhibitors. Elevated
      aldosterone levels may reflect incomplete inhibition of the vascular converting
      enzyme during long-term ACE inhibition. We simultaneously measured plasma
      aldosterone levels and the degree of inhibition of the vascular converting enzyme
      in patients with CHF. METHODS AND RESULTS: Thirty-four subjects with CHF
      receiving the maximum recommended doses of ACE inhibitors for a duration of 3 to
      105 months were studied. The pressor response to exogenous angiotensin I (AI) was
      measured and normalized for the pressor response to angiotensin II (AII) to
      assess inhibition of the vascular converting enzyme (AII/AI ratio). Aldosterone
      levels were determined by solid-phase radioimmunoassay. Eleven of the 34 subjects
      had plasma aldosterone levels above the upper limit of normal, ie, >15.0 ng/dL.
      Seven of these 11 subjects (64%) had an AII/AI ratio < or =0.05, indicating
      complete inhibition of the vascular converting enzyme. In the entire cohort, the
      AII/AI ratio did not correlate with the duration of ACE inhibitor therapy.
      CONCLUSIONS: Plasma aldosterone levels are elevated in patients with CHF during
      long-term ACE inhibitor therapy despite complete inhibition of the vascular
      converting enzyme. Complete inhibition of the vascular converting enzyme does not
      obviate the need for aldosterone receptor blockade in patients with CHF.

PMID- 12196329
TI  - Impact of community-wide police car deployment of automated external
      defibrillators on survival from out-of-hospital cardiac arrest.
AB  - BACKGROUND: Disappointing survival rates from out-of-hospital cardiac arrests
      encourage strategies for faster defibrillation, such as use of automated external
      defibrillators (AEDs) by nonconventional responders. METHODS AND RESULTS: AEDs
      were provided to all Miami-Dade County, Florida, police. AED-equipped police (P
      AED) and conventional emergency medical rescue (EMS) responders are
      simultaneously deployed to possible cardiac arrests. Times from 9-1-1 contact to
      the scene were compared for P-AED and concurrently deployed EMS, and both were
      compared with historical EMS experience. Survival with P-AED was compared with
      outcomes when EMS was the sole responder. Among 420 paired dispatches of P-AED
      and EMS, the mean+/-SD P-AED time from 9-1-1 call to arrival at the scene was
      6.16+/-4.27 minutes, compared with 7.56+/-3.60 minutes for EMS (P<0.001). Police
      arrived first to 56% of the calls. The time to first responder arrival among P
      AED and EMS was 4.88+/-2.88 minutes (P<0.001), compared with a historical
      response time of 7.64+/-3.66 minutes when EMS was the sole responder. A 17.2%
      survival rate was observed for victims with ventricular fibrillation or pulseless
      ventricular tachycardia (VT/VF), compared with 9.0% for standard EMS before P-AED
      implementation (P=0.047). However, VT/VF benefit was diluted by the observation
      that 61% of the initial rhythms were nonshockable, reducing the absolute survival
      benefit among the total study population to 1.6% (P-AED, 7.6%; EMS, 6.0%).
      CONCLUSIONS: P-AED establishes a layer of responders that generate improved
      response times and survival from VT/VF. There was no benefit for victims with
      nonshockable rhythms.

PMID- 12196330
TI  - Tripling survival from sudden cardiac arrest via early defibrillation without
      traditional education in cardiopulmonary resuscitation.
AB  - BACKGROUND: Early defibrillation is the most important intervention affecting
      survival from sudden cardiac arrest (SCA). To improve public access to early
      defibrillation, we established Piacenza Progetto Vita (PPV), the first system of
      out-of-hospital early defibrillation by first-responder volunteers. METHODS AND
      RESULTS: The system serves a population of 173 114 residents in the Piacenza
      region of Italy. Equipment for the system comprises 39 semiautomatic external
      biphasic defibrillators (AEDs): 12 placed in high-risk locations, 12 in lay
      staffed ambulances, and 15 in police cars; 1285 lay volunteers trained in use of
      the AED, without traditional education in cardiac pulmonary resuscitation,
      responded to all cases of suspected SCA, in coordination with the Emergency
      Medical System (EMS). During the first 22 months, 354 SCA occurred (72+/-12
      years, 73% witnessed). The PPV volunteers treated 143 SCA cases (40.4%), with an
      EMS call-to-arrival time of 4.8+/-1.2 minutes (versus 6.2+/-2.3 minutes for EMS,
      P=0.05). Overall survival rate to hospital discharge was tripled from 3.3% (7 of
      211) for EMS intervention to 10.5% (15 of 143) for PPV intervention (P=0.006).
      The survival rate for witnessed SCA was tripled by PPV: 15.5% versus 4.3% in the
      EMS-treated group (P=0.002). A "shockable" rhythm was present in 23.8% (34 of
      143) of the PPV patients versus 15.6% (33 of 211) of the EMS patients (P=0.055).
      The survival rate from shockable dysrhythmias was higher for PPV versus EMS:
      44.1% (15 of 34) versus 21.2% (7 of 33), P=0.046. The neurologically intact
      survival rate was higher in PPV-treated versus EMS-treated patients: 8.4% (12 of
      143) versus 2.4% (5 of 211), P=0.009. CONCLUSIONS: Broad dissemination of AEDs
      for use by nonmedical volunteers enabled early defibrillation and tripled the
      survival rate for out-of-hospital SCA.

PMID- 12196331
TI  - Association of Chlamydia pneumoniae with coronary artery disease and its
      progression is dependent on the modifying effect of mannose-binding lectin.
AB  - BACKGROUND: The possible association between coronary artery disease (CAD) and
      Chlamydia pneumoniae (C pneumoniae) infection is controversial. On the basis of
      the recent suggestion that mannose-binding lectin (MBL) variant alleles are
      related to an increased risk of severe atherosclerosis, and on the in vitro
      interaction of MBL with C pneumoniae, we asked whether MBL might contribute to
      CAD in conjunction with C pneumoniae. METHODS AND RESULTS: Antibodies to C
      pneumoniae were measured by immunofluorescence and MBL alleles were determined by
      polymerase chain reaction technique in samples from 210 patients with CAD and 257
      healthy subjects from Hungary collected between 1995 and 1996. A higher
      percentage of patients with CAD were anti-C pneumoniae positive as compared with
      the control group (P=0.058). However, at logistic regression analysis adjusted to
      age, sex, and serum lipid levels, this difference was confined only to subjects
      carrying MBL variant alleles (P=0.035, odds ratio 2.63, [95% CI: 1.07 to 6.45]).
      In contrast, no significant difference was seen in those homozygous for the
      normal MBL allele (P=0.412). During a 65+/-5.8-month follow-up period, major
      outcomes (new myocardial infarction, and/or bypass operation or cardiovascular
      death) occurred in 11 C pneumoniae positive and 3 C pneumoniae negative patients.
      In the C pneumoniae positive group, the odds ratio of development of outcomes was
      3.27 (95% CI: 1.10 to 9.71, P=0.033) in the carriers of the MBL variant alleles
      compared with the homozygous carriers of the normal MBL allele. CONCLUSIONS:
      These results indicate that infection with C pneumoniae leads mainly to the
      development and progression of severe CAD in patients with variation in the MBL
      gene.

PMID- 12196332
TI  - Influence of lipid-lowering therapy on the progression of coronary artery
      calcification: a prospective evaluation.
AB  - BACKGROUND: Coronary calcification measured by fast computed tomography
      techniques is a surrogate marker of coronary atherosclerotic plaque burden. In a
      cohort study, we prospectively investigated whether lipid-lowering therapy with a
      cholesterol synthesis enzyme inhibitor reduces the progression of coronary
      calcification. METHODS AND RESULTS: In 66 patients with coronary calcifications
      in electron beam tomography (EBT), LDL cholesterol >130 mg/dL, and no lipid
      lowering treatment, the EBT scan was repeated after a mean interval of 14 months
      and treatment with cerivastatin was initiated (0.3 mg/d). After 12 months of
      treatment, a third EBT scan was performed. Coronary calcifications were
      quantified using a volumetric score. Cerivastatin therapy lowered the mean LDL
      cholesterol level from 164+/-30 to 107+/-21 mg/dL. The median calcified volume
      was 155 mm3 (range, 15 to 1849) at baseline, 201 mm3 (19 to 2486) after 14 months
      without treatment, and 203 mm3 (15 to 2569) after 12 months of cerivastatin
      treatment. The median annualized absolute increase in coronary calcium was 25 mm3
      during the untreated versus 11 mm3 during the treatment period (P=0.01). The
      median annual relative increase in coronary calcium was 25% during the untreated
      versus 8.8% during the treatment period (P<0.0001). In 32 patients with an LDL
      cholesterol level <100 mg/dL under treatment, the median relative change was 27%
      during the untreated versus -3.4% during the treatment period (P=0.0001).
      CONCLUSIONS: Treatment with the cholesterol synthesis enzyme inhibitor
      cerivastatin significantly reduces coronary calcium progression in patients with
      LDL cholesterol >130 mg/dL.

PMID- 12196333
TI  - Accuracy of contrast-enhanced magnetic resonance imaging in predicting
      improvement of regional myocardial function in patients after acute myocardial
      infarction.
AB  - BACKGROUND: Contrast-enhanced (CE) MRI demonstrates a pattern of hypoenhancement
      early after contrast injection in acute myocardial infarction (MI) and a pattern
      of hyperenhancement late after contrast injection. Because the significance of
      these CE patterns for myocardial viability remains debated, we evaluated their
      diagnostic accuracy to quantitatively predict late functional improvement of
      regional contractility. METHODS AND RESULTS: Twenty patients underwent CE and
      tagged MRI at 4 days and again at 7 months after acute MI. Resting
      circumferential shortening strain (Ecc) was analyzed in 24 segments per patient,
      and its improvement was correlated with the presence or absence of the CE
      patterns. Immediately after MI, 389 segments were considered dysfunctional
      because of having less than mean+/-2 SD Ecc of the remote region (-18+/-4%). At
      follow-up, significant improvement of Ecc occurred in 170 dysfunctional segments
      with normal CE (from -4+/-7% to -12+/-7%, P<0.001) but not in 60 segments with
      early hypoenhancement (from -2+/-6% to -6+/-9% Ecc, P=NS). In 240 dysfunctional
      segments with delayed hyperenhancement, the improvement of Ecc (from -2+/-6% to 
      5+/-8%, P<0.001) decreased with increasing transmural extent of hyperenhancement.
      Receiver operating characteristic analysis demonstrated that absence of delayed
      hyperenhancement, compared with absence of early hypoenhancement, had better
      sensitivity (82% versus 19%, respectively; P<0.001) and accuracy (74% versus 49%,
      respectively; P<0.001) in predicting recovery of Ecc to any given level.
      CONCLUSIONS: Compared with lack of early hypoenhancement, lack of delayed
      hyperenhancement has better diagnostic accuracy in predicting functional
      improvement in dysfunctional segments. The early hypoenhanced regions, which
      represent only the fraction of infarcted tissue with concomitant microvascular
      obstruction, greatly underestimate the amount of irreversibly injured myocardium
      present after acute MI.

PMID- 12196334
TI  - Randomized trial of 90Sr/90Y beta-radiation versus placebo control for treatment
      of in-stent restenosis.
AB  - BACKGROUND: After conventional treatment of in-stent restenosis, the incidence of
      recurrent clinical restenosis may approach 40%. We report the first multicenter,
      blinded, and randomized trial of intracoronary radiation with the use of a
      90Sr/90Y beta-source for the treatment of in-stent restenosis. METHODS AND
      RESULTS: After successful catheter-based treatment of in-stent restenosis, 476
      patients were randomly assigned to receive an intracoronary catheter containing
      either 90Sr/90Y (n=244) or placebo (n=232) sources. The prescribed dose 2 mm from
      the center of the source was 18.4 Gy for vessels between 2.70 and 3.35 mm in
      diameter and 23.0 Gy for vessels between 3.36 and 4.0 mm. The primary end point,
      ie, clinically driven target-vessel revascularization by 8 months, was observed
      in 56 (26.8%) of the patients assigned to placebo and 39 (17.0%) of the patients
      assigned to radiation (P=0.015). The incidence of the composite including death,
      myocardial infarction, and target-vessel revascularization was observed in 60
      (28.7%) of the patients assigned to placebo and 44 (19.1%) of the patients
      assigned to radiation (P=0.024). Binary 8-month angiographic restenosis (> or
      =50% diameter stenosis) within the entire segment treated with radiation was
      reduced from 45.2% in the placebo-treated patients to 28.8% in the 90Sr/90Y
      treated patients (P=0.001). Stent thromboses occurred in 1 patient assigned to
      placebo <24 hours after the procedure and in 1 patient assigned to 90Sr/90Y at
      day 244. CONCLUSIONS: The results of this study demonstrated that beta-radiation
      using 90Sr/90Y is both safe and effective for preventing recurrence in patients
      with in-stent restenosis.

PMID- 12196336
TI  - Patterns of coronary compromise resulting in acute right ventricular ischemic
      dysfunction.
AB  - BACKGROUND: Although proximal right coronary artery (RCA) occlusion is the
      culprit commonly responsible for acute right ventricular (RV) infarction (RVI),
      the severity of RV dysfunction ranges broadly. This study was designed to
      delineate the patterns of coronary compromise that determine the magnitude of RV
      ischemic dysfunction. METHODS AND RESULTS: In 125 patients with acute inferior
      myocardial infarction undergoing emergency angiography, the culprit infarct
      lesion was identified, RV branch flow assessed (TIMI flows and frame counts), and
      individual patient RV perfusion indices calculated by separately averaging the
      branch flows and frame counts, which were correlated with RV wall motion by
      ultrasound. RVI occurred in 53 (42%) patients, with the RCA as the culprit vessel
      and the lesion sufficiently proximal to compromise flow in at least one RV branch
      in all cases, thereby resulting in depressed RV perfusion (flow index, 0.7+/
      0.2). In patients without RVI, the RCA was the culprit in 89%; the circumflex, in
      11%. RCA culprits were proximal in 19% of such cases, with lack of RVI explained
      by preserved RV perfusion (flow index, 2.7+/-0.3; P=0.001) attributable to at
      least 1 patent RV branch, spontaneous reperfusion, or prominent collaterals.
      Overall, there was a strong correlation between RV perfusion and wall motion
      (Spearman correlation coefficient=0.79). CONCLUSIONS: Proximal RCA occlusion
      compromising RV branch perfusion commonly results in RV ischemic dysfunction. In
      some cases with proximal RCA culprits, collaterals or spontaneous reperfusion
      preserve RV performance.

PMID- 12196335
TI  - Sildenafil effects on exercise, neurohormonal activation, and erectile
      dysfunction in congestive heart failure: a double-blind, placebo-controlled,
      randomized study followed by a prospective treatment for erectile dysfunction.
AB  - BACKGROUND: Erectile dysfunction (ED) is common in patients with congestive heart
      failure (CHF). ED reduces quality of life, and it may affect compliance, thereby
      impairing the success of CHF treatment. METHODS AND RESULTS: In the first phase
      (fixed-dose double-blind, randomized, placebo-controlled, two-way crossover
      study), we studied in 23 men with CHF the effects of 50 mg sildenafil on exercise
      and neurohormonal activation. Patients underwent a treadmill 6-minute
      cardiopulmonary walking (6'WT) test followed by a maximal cardiopulmonary
      exercise test (ET). In the second phase, patients received sildenafil, taken as
      required for ED. Sildenafil reduced the heart rate (HR) (bpm) before the 6'WT
      (from 75+/-15 to 71+/-14, P=0.02) and ET (from 75+/-15 to 71+/-15, P=0.02); the
      systolic blood pressure (mm Hg) before the 6'WT (from 116+/-18 to 108+/-18,
      P=0.004) and ET (from 116+/-15 to 108+/-17, P=0.001); the diastolic blood
      pressure before the 6'WT (from 69+/-9 to 63+/-11, P=0.01) and ET (from 70+/-8 to
      65+/-10, P=0.004); and the Ve/VCO2 slope during the 6'WT (from 32+/-7 to 31+/-6,
      P=0.04) and ET (from 33+/-8 to 31+/-5, P=0.03). Sildenafil attenuated the HR
      increment during the 6'WT (P=0.003) and ET (P=0.000). Sildenafil increased the
      peak *O2 from 16.6+/-3.4 to 17.7+/-3.4 mL/kg per min (P=0.025) and the exercise
      time from 12.3+/-3.4 to 13.7+/-3.2 minutes (P=0.003). Sildenafil improved most
      scores of International Index of Erectile Function. CONCLUSIONS: Sildenafil was
      tolerated and effective for ED treatment in CHF, and improved the exercise
      capacity. The reduction of HR during exercise with sildenafil could theoretically
      decrease the myocardial oxygen consumption during sexual activity.

PMID- 12196337
TI  - Chronobiological patterns of acute aortic dissection.
AB  - BACKGROUND: Chronobiological rhythms have been shown to influence the occurrence
      of a variety of cardiovascular disorders. However, the effects of the time of the
      day, the day of the week, or monthly/seasonal changes on acute aortic dissection
      (AAD) have not been well studied. METHODS AND RESULTS: Accordingly, we evaluated
      957 patients enrolled in the International Registry of Acute Aortic Dissection
      (IRAD) between 1996 and 2000 (mean age 62+/-14 years, type A 61%). A chi2 test
      for goodness of fit and partial Fourier analysis were used to evaluate
      nonuniformity and rhythmicity of AAD during circadian, weekly, and monthly
      periods. A significantly higher frequency of AAD occurred from 6:00 AM to 12:00
      noon compared with other time periods (12:00 noon to 6:00 PM, 6:00 PM to 12:00
      midnight, and 12:00 midnight to 6:00 AM; P<0.001 by chi2 test). Fourier analysis
      showed a highly significant circadian variation (P<0.001) with a peak between
      8:00 AM and 9:00 AM. Although no significant variation was found for the day of
      the week, the frequency of AAD was significantly higher during winter (P=0.008
      versus other seasons by chi2 test). Fourier analysis confirmed this monthly
      variation with a peak in January (P<0.001). Subgroup analysis identified a
      significant association for all subgroups with circadian rhythmicity. However,
      seasonal/monthly variations were observed only among patients aged <70 years,
      those with type B AAD, and those without hypertension or diabetes. CONCLUSIONS:
      Similar to other cardiovascular conditions, AAD exhibits significant circadian
      and seasonal/monthly variations. Our findings may have important implications for
      the prevention of AAD by tailoring treatment strategies to ensure maximal
      benefits during the vulnerable periods.

PMID- 12196338
TI  - Disproportionate decrease in alpha- compared with beta-adrenergic sensitivity in
      the dorsal hand vein in pregnancy favors vasodilation.
AB  - BACKGROUND: Altered vascular responses to adrenergic agonists during pregnancy
      are thought to play an important role in the regulation of blood pressure and
      placental blood flow. Because alpha1-adrenergic and beta2-adrenergic sensitivity
      act in opposing directions to determine vascular tone, we simultaneously
      evaluated alpha-adrenergic-mediated vasoconstriction and beta-adrenergic-mediated
      vasodilation in dorsal hand veins during and after pregnancy. METHODS AND
      RESULTS: Twenty healthy pregnant women were studied at 32 to 37 weeks of
      gestation and again 12 weeks after delivery. Vascular response to phenylephrine
      (PE) and isoproterenol (ISO) was measured in a dorsal hand vein using the linear
      variable differential transformer technique. The dose of PE resulting in 50%
      constriction (CD50) was determined. The response to ISO was measured after the PE
      preconstriction. Pregnant and postpartum values, expressed as geometric mean (95%
      CI), were compared by paired t test. alpha-Adrenergic sensitivity during
      pregnancy (CD50 2.7 micro g/min [95% CI, 1.5 to 5.0]) was markedly decreased,
      approximately 7-fold, compared with postpartum (0.4 micro g/min [95% CI, 0.3 to
      0.7] [P<0.01]). beta-Adrenergic vasodilation was also attenuated during
      pregnancy. The ED50 of ISO (dose of ISO resulting in 50% of the maximal response,
      E(max)) was greater during pregnancy (20 ng/min [95% CI, 11 to 35]) than
      postpartum (8 ng/min [95% CI, 5 to 12]) (P<0.05). ISO E(max) was also
      significantly less during pregnancy (81% [95% CI, 65 to 97] compared with
      postpartum (105% [95% CI, 97 to 113]) (P<01.01). CONCLUSIONS: Normal pregnancy is
      characterized by decreased venous sensitivity to both alpha1-adrenoceptor
      mediated vasoconstriction and beta2-adrenoceptor-mediated vasodilation. The
      greater decrease in alpha1 compared with beta2 response may contribute to the
      vasodilated state characteristic of human pregnancy.

PMID- 12196339
TI  - Percutaneous transcatheter closure of patent foramen ovale in patients with
      paradoxical embolism.
AB  - BACKGROUND: Percutaneous transcatheter closure of patent foramen ovale (PFO) is
      used as an alternative to surgery or long-term anticoagulation for the treatment
      of patients with paradoxical embolism and PFO. METHODS AND RESULTS: We report the
      immediate and long-term clinical and echocardiographic outcome of 110 consecutive
      patients (58 males, mean age 47+/-14 years) who underwent transcatheter closure
      of PFO because of paradoxical embolism between 1995 and 2001. Procedural success,
      defined as successful deployment of the device and effective occlusion (no, or
      trivial, shunt after device placement), was achieved in all (100%) patients.
      There was no in-hospital mortality, 1 device migration requiring surgical
      intervention (0.9%), and 1 episode of cardiac tamponade (0.9%) requiring
      pericardiocentesis. A progressive increment in full occlusion was observed (44%,
      51%, 66%, and 71% at 1 day, 6 months, and 1 and 2 years, respectively, after
      device placement). At a mean follow-up of 2.3 years, 2 patients experienced
      recurrent neurological events (1 fatal stroke and 1 transient ischemic attack),
      representing an annual risk of recurrence of 0.9%. In addition, 4 (3.6%) of the
      patients required reintervention for device malalignment or significant shunt.
      Kaplan-Meier analysis showed a freedom from recurrent embolic events and
      reintervention of 96% and 90% at 1 and 5 years, respectively. CONCLUSIONS:
      Transcatheter closure of PFO is a safe and effective therapy for patients with
      paradoxical embolism and PFO. It is associated with a high success rate, low
      incidence of hospital complications, and low frequency of recurrent systemic
      embolic events.

PMID- 12196340
TI  - Influenza infection promotes macrophage traffic into arteries of mice that is
      prevented by D-4F, an apolipoprotein A-I mimetic peptide.
AB  - BACKGROUND: We reported that HDL loses its antiinflammatory properties during
      acute influenza A infection in mice, and we hypothesized that these changes might
      be associated with increased trafficking of macrophages into the artery wall. The
      present study tested this hypothesis. METHODS AND RESULTS: D-4F, an
      apolipoprotein A-I mimetic peptide, or vehicle in which it was dissolved (PBS)
      was administered daily to LDL receptor-null mice after a Western diet and after
      influenza infection. D-4F treatment increased plasma HDL cholesterol and
      paraoxonase activity compared with PBS and inhibited increases in LDL cholesterol
      and peak levels of interleukin-6 after infection. Lung viral titers were reduced
      by 50% in mice receiving D-4F. Injection of female mice with male macrophages,
      which were detected with real-time polymerase chain reaction to measure the male
      Sry gene, revealed a marked increase in macrophage traffic into the aortic arch
      and innominate arteries after infection that was prevented by administration of D
      4F. CONCLUSIONS: We conclude that loss of antiinflammatory properties of HDL
      after influenza infection in mice is associated with increased arterial
      macrophage traffic that can be prevented by administration of D-4F.

PMID- 12196342
TI  - Hypercholesterolemia in minipigs impairs left ventricular response to stress:
      association with decreased coronary flow reserve and reduced capillary density.
AB  - BACKGROUND: Hypercholesterolemia induces functional and structural changes of the
      microvasculature and reduces coronary flow reserve in humans and experimental
      animals. The effect of hypercholesterolemia on left ventricular (LV) function in
      the absence of coronary stenosis is, however, unknown. Our objective was
      therefore to assess the effect of hypercholesterolemia and cholesterol withdrawal
      on LV function in the presence of advanced coronary plaques that do not cause
      stenosis. METHODS AND RESULTS: Twenty-eight minipigs on cholesterol diet for 34
      weeks and 16 control pigs were studied. Seven hypercholesterolemic pigs were
      withdrawn from the diet for 26 weeks. LV function was assessed with cine-MRI,
      myocardial blood flow with colored microspheres, and capillary density with
      immunohistochemistry, and microvascular endothelial cell apoptosis with terminal
      dUTP nick-end labeling staining. Hypercholesterolemia (17+/-8 versus 268+/-150
      versus 12+/-10 mg/dL LDL cholesterol, control versus hypercholesterolemic versus
      cholesterol withdrawal; P<0.001) induced atherosclerosis but not stenosis in the
      left coronary artery. Baseline cardiac output, ejection fraction, and stroke
      volume were similar in control and hypercholesterolemic pigs. In dobutamine
      stress test, cardiac output (P<0.05) and stroke volume (P<0.01) were lower in
      hypercholesterolemic pigs compared with controls. The impaired response to
      dobutamine was reversible by dietary cholesterol withdrawal. Hypercholesterolemia
      reduced endomyocardial coronary flow reserve (P<0.01) and capillary density
      (P<0.05) and induced capillary endothelial cell apoptosis. Hypercholesterolemic
      pigs failed to reduce vascular resistance in response to increased LV workload
      and pharmacological vasodilation. CONCLUSION: LDL hypercholesterolemia in
      minipigs impaired LV response to dobutamine stress in the absence of coronary
      stenosis.

PMID- 12196341
TI  - Constitutive human telomerase reverse transcriptase expression enhances
      regenerative properties of endothelial progenitor cells.
AB  - BACKGROUND: The regulatory molecule for cell life span, telomerase, was modified
      by human telomerase reverse transcriptase (hTERT) gene transfer to investigate
      its effect on regenerative properties of endothelial progenitor cells (EPCs) in
      neovascularization. METHODS AND RESULTS: Telomerase activity was enhanced in
      hTERT-transduced EPCs (Td-TERTs) (1.2-fold versus no transduced EPCs [no-Td] and
      1.2-fold versus GFP-transduced EPCs [Td/GFPs] at day 8; 5.2-fold versus no-Td and
      4.8-fold versus Td/GFP at day 21, respectively) Mitogenic capacity in Td/TERTs
      exceeded that in Td/GFPs at day 8 (0.62+/-0.02 versus 0.53+/-0.01, respectively;
      P<0.01). Vascular endothelial growth factor-induced cell migration in EPCs was
      markedly enhanced by hTERT overexpression (Td/TERTs versus Td/GFPs, 292+/-12
      versus 174+/-6 cells, respectively; P<0.01). hTERT overexpression has rescued
      EPCs from starvation-induced cell apoptosis, an outcome that was further enhanced
      in response to vascular endothelial growth factor. The colony appearance of
      totally differentiated endothelial cells (tdECs) was detected before day 30 only
      in Td/TERT, whereas no tdEC colonies could be detected in both Td/GFPs and no
      Tds. Finally, we investigated in vivo transplantation of heterologous EPCs.
      Td/TERTs dramatically improved postnatal neovascularization in terms of limb
      salvage by 4-fold in comparison with that of Td/GFPs; limb perfusion was measured
      by laser Doppler (0.77+/-0.10 versus 0.47+/-0.06; P=0.02), and capillary density
      (224+/-78 versus 90+/-40 capillaries/mm2; P<0.01). CONCLUSIONS: These findings
      provide the novel evidence that telomerase activity contributes to EPC angiogenic
      properties; mitogenic activity, migratory activity, and cell survival. This
      enhanced regenerative activity of EPCs by hTERT transfer will provide novel
      therapeutical strategy for postnatal neovascularization in severe ischemic
      disease patients.

PMID- 12196343
TI  - Accumulation of foam cells in liver X receptor-deficient mice.
AB  - BACKGROUND: The nature of some of the target genes for liver X receptors (LXRs)
      alpha and -beta, such as sterol regulatory element binding protein-1 and ATP
      binding cassette transporter proteins, suggests a pivotal role of these nuclear
      receptors in the regulation of fatty acid and cholesterol homeostasis. The
      present study aimed to elucidate the physiological relevance of both LXRs with
      regard to lipid metabolism and macrophage cholesterol efflux. METHODS AND
      RESULTS: Mice depleted for LXRalpha, LXRbeta, or both were fed low-fat rodent
      chow for 18 months before investigations. The combined deficiency of LXRalpha and
      LXRbeta was linked to impaired triglyceride metabolism, increased LDL and reduced
      HDL cholesterol levels, and cholesterol accumulation in macrophages (foam cells)
      of the spleen, lung, and arterial wall. CONCLUSIONS: Our data demonstrate the
      physiological importance of both LXRs in lipid metabolism and strongly indicate
      that both LXRs have a protective role against the development of atherosclerosis.

PMID- 12196344
TI  - Heterozygous cellular glutathione peroxidase deficiency in the mouse:
      abnormalities in vascular and cardiac function and structure.
AB  - BACKGROUND: Oxidant stress has been implicated in the pathogenesis of
      atherothrombosis and other vascular disorders accompanied by endothelial
      dysfunction. Glutathione peroxidases (GPx) play an important role in the cellular
      defense against oxidant stress by utilizing glutathione (GSH) to reduce lipid
      hydroperoxides and hydrogen peroxide to their corresponding alcohols. Cellular
      GPx (GPx-1) is the principal intracellular isoform of GPx. We hypothesized that
      GPx-1 deficiency per se induces endothelial dysfunction and structural vascular
      abnormalities through increased oxidant stress. METHODS AND RESULTS: A murine
      model of heterozygous deficiency of GPx-1 (GPx(+/-)) was investigated to examine
      this hypothesis. Mesenteric arterioles in GPx-1(+/-) mice demonstrated
      vasoconstriction to acetylcholine compared with vasodilation in wild-type mice
      (maximal change in vessel diameter, -13.0+/-2.8% versus 13.2+/-2.8%, P<0.0001).
      We also noted an increase in the plasma and aortic levels of the isoprostane
      iPF(2alpha)-III, a marker of oxidant stress, in GPx-1(+/-) mice compared with
      wild-type mice (170.4+/-23 pg/mL plasma versus 98.7+/-7.1 pg/mL plasma, P<0.03;
      11.7+/-0.87 pg/mg aortic tissue versus 8.2+/-0.55 pg/mg aortic tissue, P<0.01).
      Histological sections from the coronary vasculature of GPx-1(+/-) mice show
      increased perivascular matrix deposition, an increase in the number of
      adventitial fibroblasts, and intimal thickening. These structural abnormalities
      in the myocardial vasculature were accompanied by diastolic dysfunction after
      ischemia-reperfusion. CONCLUSIONS: These findings demonstrate that heterozygous
      deficiency of GPx-1 leads to endothelial dysfunction, possibly associated with
      increased oxidant stress, and to significant structural vascular and cardiac
      abnormalities. These data illustrate the importance of this key antioxidant
      enzyme in functional and structural responses of the mammalian cardiovascular
      system.

PMID- 12196345
TI  - Long-term survival and hemodynamics after endothelin-a receptor antagonism and
      angiotensin-converting enzyme inhibition in rats with chronic heart failure:
      monotherapy versus combination therapy.
AB  - BACKGROUND: In patients with congestive heart failure (CHF) receiving ACE
      inhibitors, acute administration of selective endothelin (ET) antagonists
      additionally improves systemic and cardiac hemodynamics. We investigated, in a
      rat model of CHF, whether such acute synergistic effects are sustained and
      accompanied, in the long term, by an additional limitation of left ventricular
      remodeling or an increase in survival. METHODS AND RESULTS: Rats were subjected
      to coronary artery ligation and treated for 3 or 9 months with vehicle or with
      the ACE inhibitor trandolapril (Tr) (0.3 mg/kg(-1) per day(-1)), the ET(A)
      antagonist LU 135252 (LU, 30 mg/kg(-1) per day(-1)), or their combination
      starting 7 days after ligation. After 3 months, the combination decreased LV
      systolic- and end-diastolic pressures (-32% and -80%, respectively) more markedly
      than Tr (-21% and -61%, respectively) or LU alone (-14% and -48%, respectively).
      Echocardiographic studies revealed that all treatments limited LV dilatation and
      increased LV fractional shortening and cardiac index. All treatments equally
      reduced left ventricular collagen density, whereas only Tr or the combination
      reduced LV weight. Finally, although LU did not modify long-term survival, Tr and
      the combination of Tr with LU induced a similar improvement of survival.
      CONCLUSIONS: In this rat model, long-term combined administration of an ET(A)
      antagonist and an ACE inhibitor induces additional effects in terms of systemic
      and cardiac hemodynamics; however, this is not associated with an additional
      increase in long-term survival.

PMID- 12196347
TI  - Principles from clinical trials relevant to clinical practice: Part II.

PMID- 12196346
TI  - Distinct renal injury in early atherosclerosis and renovascular disease.
AB  - BACKGROUND: Atherosclerotic renovascular disease may augment deterioration of
      renal function and ischemic nephropathy compared with other causes of renal
      artery stenosis (RAS), but the underlying mechanisms remain unclear. This study
      was designed to test the hypothesis that concurrent early atherosclerosis and
      hypoperfusion might have greater early deleterious effects on the function and
      structure of the stenotic kidney. METHODS AND RESULTS: Regional renal
      hemodynamics and function at baseline and during vasoactive challenge
      (acetylcholine or sodium nitroprusside) were quantified in vivo in pigs by
      electron-beam computed tomography after a 12-week normal (n=7) or
      hypercholesterolemic (HC, n=7) diet, RAS (n=6), or concurrent HC and a similar
      degree of RAS (HC+RAS, n=7). Flash-frozen renal tissue was studied ex vivo. Basal
      cortical perfusion and single-kidney glomerular filtration rate (GFR) were
      decreased similarly in the stenotic RAS and HC+RAS kidneys, but tubular fluid
      reabsorption was markedly impaired only in HC+RAS. Perfusion responses to
      challenge were similarly blunted in the experimental groups. Stimulated GFR
      increased in normal, HC, and RAS (38.3+/-3.6%, 36.4+/-7.6%, and 60.4+/-9.3%,
      respectively, P<0.05), but not in HC+RAS (6.5+/-15.1%). These functional
      abnormalities in HC+RAS were accompanied by augmented perivascular,
      tubulointerstitial, and glomerular fibrosclerosis, inflammation, systemic and
      tissue oxidative stress, and tubular expression of nuclear factor-kappaB and
      inducible nitric oxide synthase. CONCLUSIONS: Early chronic HC+RAS imposes
      distinct detrimental effects on renal function and structure in vivo and in
      vitro, evident primarily in the tubular and glomerular compartments. Increased
      oxidative stress may be involved in the proinflammatory and progrowth changes
      observed in the stenotic HC+RAS kidney, which might potentially facilitate the
      clinically observed progression to end-stage renal disease.

PMID- 12196348
TI  - Images in cardiovascular medicine. Stent inflammation: stent footprint in
      restenotic tissue retrieved by directional atherectomy.

PMID- 12196349
TI  - Images in cardiovascular medicine. Pulmonary site bioprosthesis: failure at 15
      years.

PMID- 12196350
TI  - Systemic inflammation, atrial fibrillation, and cancer.

PMID- 12196351
TI  - Anatomy of a criss-cross heart.

PMID- 12196352
TI  - Plasma leptin levels and coronary heart disease.

PMID- 12196353
TI  - Left ventricular remodeling in elite athletes.

PMID- 12196354
TI  - Wider use of automated external defibrillators?

PMID- 12196356
TI  - Dose density and dose intensity: where does CHOP go from here?

PMID- 12196357
TI  - The clinical value of nuclear medicine in the assessment of irradiation-induced
      and anthracycline-associated cardiac damage.
AB  - Two groups of patients, those treated for Hodgkin's disease and breast cancer,
      are particularly at risk of developing late myocardial damage, since radiotherapy
      (RT) techniques for both patient groups may include (large) parts of the heart,
      and adjuvant systemic therapy is frequently administered to these patients, in
      particular anthracycline-containing chemotherapy. Available literature on the
      monitoring and prediction of RT-induced and anthracycline-associated cardiac
      damage using nuclear medicine techniques is presented. Based on relevant studies,
      the risk of overall cardiac disease post-RT and overt congestive heart failure
      during anthracycline-containing chemotherapy is probably low. Conventional
      nuclear medicine imaging, i.e. myocardial perfusion scintigraphy, may be of
      complementary use to echocardiographical evaluation for routine follow-up after
      RT with modern techniques, in a subgroup of patients with known cardiovascular
      risk factors. Left ventricle ejection fraction (LVEF) measurements, as assessed
      by radionuclide angiography for the monitoring of anthracycline-associated
      cardiac injury, are not very sensitive and early detection will probably be
      enhanced by combining LVEF measurements with other cardiac function parameters.
      Also, it may be expected that nuclear medicine techniques using molecular
      radioligands will constitute an essential future step in the evaluation of
      subclinical cardiac injury afforded by the combined effect of RT and cardiotoxic
      chemotherapy.

PMID- 12196358
TI  - Intensified CHOP regimen in aggressive lymphomas: maximal dose intensity and dose
      density of doxorubicin and cyclophosphamide.
AB  - BACKGROUND: Following our previous study of CHOP (cyclophosphamide, doxorubicin,
      vincristine and prednisone) intensification in non-Hodgkin's lymphoma (NHL), in
      the present report we attempted to further increase dose intensity by shortening
      the between-course intervals with the support of growth factors. PATIENTS AND
      METHODS: A total of 67 patients were enrolled. With a fixed dose of doxorubicin
      75 mg/m(2), cyclophosphamide (CTX) was started at a dose of 1750 mg/m(2) and
      increased by 250 mg/m(2) in consecutive cohorts of patients provided that no dose
      limiting toxicity occurred. After the maximal tolerated dose (MTD) had been
      identified, this was used to treat more patients in order to confirm the
      feasibility of the regimen on a large scale, with the number of cycles being
      varied on the basis of disease extension. RESULTS: Twenty-three cases were
      enrolled in the CTX dose finding phase. Dose-limiting non-hematological toxicity
      occurred at 2250 mg/m(2). As the intermediate level of 2000 mg/m(2) had a
      borderline toxicity profile, a CTX dose of 1750 mg/m(2) was defined as the MTD. A
      total of 53 patients then received the MTD during the course of the study as a
      whole. At the MTD, toxicity was acceptable. Only 10 of 189 cycles (4%) required
      hospitalization due to infection or febrile neutropenia. Seventy-four percent of
      the patients achieved complete remission. Freedom from progression and overall
      survival at 12 months were 71% and 86% in the whole series, and 58% and 71% for
      high-risk cases, respectively. CONCLUSIONS: This intensified CHOP regimen is
      feasible on an outpatient basis. It can be safely considered a definitive
      treatment in patients at low and intermediate risk, and as induction before high
      dose consolidation in high-risk cases.

PMID- 12196360
TI  - Early restaging positron emission tomography with ( 18)F-fluorodeoxyglucose
      predicts outcome in patients with aggressive non-Hodgkin's lymphoma.
AB  - BACKGROUND: Less than half of all patients with aggressive non-Hodgkin's lymphoma
      (NHL) are cured with standard chemotherapy. Therefore, it is important to
      distinguish between responders to standard treatment and non-responders who may
      benefit from an early change to a more effective therapy. This study was intended
      to assess the value of a midtreatment fluorine-18 fluorodeoxyglucose positron
      emission tomography ([(18)F]FDG-PET) scan to predict clinical outcome in patients
      with aggressive NHL. PATIENTS AND METHODS: Seventy newly diagnosed patients with
      aggressive NHL, who were treated with doxorubicin-containing chemotherapy,
      underwent a [(18)F]FDG-PET scan at midtreatment. Presence or absence of abnormal
      [(18)F]FDG uptake was related to progression-free survival (PFS) and overall
      survival (OS) using Kaplan-Meier survival analysis. Multivariate analysis was
      performed to evaluate the effect of the International Prognostic Index (IPI) and
      early [(18)F]FDG-PET findings on PFS and OS. RESULTS: At midtreatment, 33
      patients showed persistent abnormal [(18)F]FDG uptake and none of these patients
      achieved a durable complete remission (CR), whereas 37 patients showed a negative
      scan; 31/37 remained in CR, with a median follow-up of 1107 days. Only 6/37
      patients either achieved a partial response or relapsed. Comparison between
      groups indicated a statistically significant association between [(18)F]FDG-PET
      findings and PFS (P <1 x 10(-5)) and OS (P <1 x 10(-5)). In multivariate
      analysis, [(18)F]FDG-PET at midtreatment was a stronger prognostic factor for PFS
      (P <1 x 10(-7)) and OS (P <9 x 10(-6)) than the IPI (P <0.11 and P <0.03,
      respectively). CONCLUSIONS: Early restaging [(18)F]FDG-PET may be used to tailor
      induction chemotherapy in patients with aggressive NHL.

PMID- 12196359
TI  - Randomized phase II study of biweekly CHOP and dose-escalated CHOP with
      prophylactic use of lenograstim (glycosylated G-CSF) in aggressive non-Hodgkin's
      lymphoma: Japan Clinical Oncology Group Study 9505.
AB  - BACKGROUND: CHOP (cyclophosphamide, doxorubicin, vincristine and prednisone) is
      accepted as the best available standard treatment for first-line chemotherapy in
      aggressive non-Hodgkin's lymphoma (NHL). However, the therapeutic efficacy of
      CHOP remains unsatisfactory, particularly in high-intermediate risk and high risk
      patients, and a new strategy is warranted in this patient population. The aim of
      the present study was to explore a suitable therapeutic-intensified regimen for
      the treatment of aggressive NHL. PATIENTS AND METHODS: Between May 1995 and July
      1998, a total of 70 patients with high-intermediate risk or high risk aggressive
      NHL, according to the International Prognostic Index, were enrolled and randomly
      assigned to receive either eight cycles of standard CHOP (cyclophosphamide 750
      mg/m(2), doxorubicin 50 mg/m(2), vincristine 1.4 mg/m(2) and prednisolone 100 mg
      for 5 days) every 2 weeks, or six cycles of dose-escalated CHOP (cyclophosphamide
      1500 mg/m(2), doxorubicin 70 mg/m(2), vincristine 1.4 mg/m(2) and prednisolone
      100 mg for 5 days) every 3 weeks. Lenograstim (glycosylated rHuG-CSF), at a dose
      of 2 micro g/kg/day s.c., was administered daily from day 3 until day 13 with
      biweekly CHOP and until day 20 with the dose-escalated CHOP. The primary endpoint
      was complete response rate. RESULTS: The complete response rate was 60% [21 of
      35; 95% confidence interval (CI) 42% to 76%] with biweekly CHOP and 51% (18 of
      35; 95% CI 34% to 69%) with dose-escalated CHOP. The major toxicity was grade 4
      neutropenia and was more frequent in the dose-escalated CHOP arm (86%) than in
      the biweekly CHOP arm (50%). Grade 4 thrombocytopenia was also more frequent in
      the dose-escalated CHOP arm (20%) than the biweekly CHOP arm (3%). Non
      hematological toxicities were acceptable in both arms. One treatment-related
      death (due to cardiac arrhythmia) was observed in a dose-escalated CHOP patient.
      Progression-free survival at 3 years was 43% (95% CI 27% to 59%) in the biweekly
      CHOP arm and 31% (95% CI 16% to 47%) in the dose-escalated CHOP arm. Although
      seven patients were deemed ineligible by central review of the pathological
      diagnosis, the results for both eligible and all enrolled patients were similar.
      CONCLUSIONS: Similar complete response rates and progression-free survival rates,
      but lower toxicity, indicated that biweekly CHOP was superior to dose-escalated
      CHOP in the treatment of aggressive NHL. Based on these results, the Lymphoma
      Study Group of the Japan Clinical Oncology Group is conducting a randomized phase
      III study comparing biweekly CHOP with standard CHOP in newly diagnosed patients
      with advanced-stage aggressive NHL.

PMID- 12196362
TI  - The International Prognostic Factors Project score for advanced Hodgkin's disease
      is useful for predicting outcome of autologous hematopoietic stem cell
      transplantation.
AB  - BACKGROUND: The International Prognostic Factors Project on Advanced Hodgkin's
      Disease developed a seven-factor prognostic score consisting of serum albumin,
      hemoglobin, gender, stage, age, leukocytosis and lymphocytopenia for newly
      diagnosed Hodgkin's disease patients who receive chemotherapy. The purpose of
      this study was to determine whether this prognostic score would also be useful
      for Hodgkin's disease patients undergoing autologous hematopoietic stem cell
      transplantation. PATIENTS AND METHODS: We performed a retrospective review of 379
      patients who had autologous transplants for Hodgkin's disease, at the University
      of Nebraska Medical Center between October 1984 and December 1999. Multivariate
      analysis was performed to determine whether the prognostic factors identified by
      the International Prognostic Factors Project adversely influenced event-free
      survival (EFS) or overall survival (OS). RESULTS: Low serum albumin, anemia, age
      and lymphocytopenia were associated with poorer EFS and OS. Gender, stage and
      leukocytosis were not associated with significantly poorer outcomes. Estimated 10
      year EFS was 38%, 23% and 7% for patients with 0-1, 2-3 or > or =4 of the adverse
      prognostic characteristics identified by the International Prognostic Factors
      Project, respectively. CONCLUSIONS: The prognostic score for advanced disease is
      also useful for relapsed and refractory Hodgkin's disease patients undergoing
      high-dose therapy followed by autologous hematopoietic stem cell transplantation.

PMID- 12196361
TI  - Randomized trial of 8-week versus 12-week VNCOP-B plus G-CSF regimens as front
      line treatment in elderly aggressive non-Hodgkin's lymphoma patients.
AB  - BACKGROUND: Among the third-generation chemotherapy regimens specifically adapted
      in the last decade for elderly aggressive non-Hodgkin's lymphoma (NHL) patients,
      we designed an 8-week cyclophosphamide, mitoxantrone, vincristine, etoposide,
      bleomycin and prednisone (VNCOP-B) plus granulocyte colony-stimulating factor (G
      CSF) regimen which, in a national multicenter trial, induced good complete
      response (CR) and relapse-free survival rates with only moderate toxic effects.
      Here we report a prospective, multicenter, randomized trial comparing the
      efficacy and toxicity of 8- and 12-week regimens of VNCOP-B plus G-CSF. PATIENTS
      AND METHODS: From February 1996 to June 2001, 306 consecutive previously
      untreated stage II-IV aggressive NHL patients > or =60 years of age were enrolled
      from 12 Italian cooperative institutions. Of the 297 evaluable patients, 149 and
      148 received 8- and 12-week regimens, respectively, of VNCOP-B. RESULTS: The CR
      rates were 63% and 56% in the 8- and 12-week groups; at a median of 32 months
      (range 3-62 months), relapse-free survival rates were 59% and 55%, respectively.
      Hematological and non-hematological toxicities were similar in both treatment
      groups. CONCLUSIONS: Our data show that extending induction treatment with the
      VNCOP-B plus G-CSF regimen from 8 to 12 weeks does not raise the CR rate or
      provide a more durable remission.

PMID- 12196363
TI  - Patterns of failure in a randomized trial of adjuvant chemotherapy in
      postmenopausal patients with early breast cancer treated with tamoxifen.
AB  - BACKGROUND: We studied the effect of adjuvant anthracycline-based chemotherapy in
      postmenopausal patients with resected early breast cancer treated with adjuvant
      tamoxifen. PATIENTS AND METHODS: The trial included 835 patients with either
      axillary lymph node involvement, or tumors with histological grade II or III.
      They were randomized after local surgery to receive either tamoxifen (TAM group)
      or tamoxifen plus chemotherapy (TAM-CT group) consisting of six courses of 5
      fluorouracil, doxorubicin and cyclophosphamide (FAC), or 5-fluorouracil,
      epidoxorubicin and cyclophosphamide (FEC). Radiotherapy was given after
      completion of adjuvant chemotherapy in the TAM-CT group and after surgery in the
      TAM group. RESULTS: The 5-year disease-free survival (DFS) rates were 73% in the
      TAM group and 79% in the TAM-CT group (log-rank test, P = 0.06). The 5-year
      overall survival rates were 82% and 87%, respectively (P = 0.06). The 5-year
      distant metastasis rates were 22% and 16% (P = 0.02), and the 5-year local
      recurrence rates were 6% and 4%, respectively (P = 0.23). There were no
      significant differences for contralateral breast cancer or other new primary
      malignancies. Chemotherapy tended to be more effective for patients who had
      tumors without estrogen receptors (trend test, P = 0.05). CONCLUSIONS:
      Anthracycline-based chemotherapy administered to postmenopausal patients
      receiving adjuvant tamoxifen gave a borderline significant benefit on overall and
      DFS, mainly by a reduction in distant metastases. Delaying radiotherapy after six
      courses of chemotherapy did not affect local control after up to 10 years of
      follow-up.

PMID- 12196364
TI  - Late effects of adjuvant chemotherapy on cognitive function: a follow-up study in
      breast cancer patients.
AB  - BACKGROUND: Neuropsychological examinations have shown an elevated risk for
      cognitive impairment 2 years after therapy in breast cancer patients randomized
      to receive adjuvant high-dose cyclophosphamide, thiotepa, carboplatin (CTC)
      chemotherapy compared with a non-treated control group of stage I breast cancer
      patients. Patients randomized to receive standard-dose fluorouracil, epirubicin,
      cyclophosphamide (FEC) chemotherapy showed no elevated risk compared with
      controls. However, breast cancer patients treated with conventional
      cyclophosphamide, methotrexate, 5-fluorouracil (CMF) chemotherapy showed a higher
      risk of cognitive impairment. The present study was designed to obtain a greater
      insight into these long-term neuropsychological sequelae following chemotherapy
      and their course in time. PATIENTS AND METHODS: At 4 years post-therapy, 22 of
      the original 34 CTC patients, 23 of 36 FEC patients, 31 of 39 CMF patients and 27
      of 34 control patients were re-examined with neuropsychological tests. RESULTS:
      Improvement in performance was observed in all chemotherapy groups, whereas in
      the control group there was a slight deterioration in test results. A
      differential attrition was observed among the groups, with a relatively high
      percentage of initially cognitively impaired patients from the CTC group dropping
      out due to factors related to disease progression. CONCLUSIONS: The results
      suggest that cognitive dysfunction following adjuvant chemotherapy in breast
      cancer patients may be transient. Additional studies are needed to investigate
      the differential attrition of patients with cognitive impairment.

PMID- 12196365
TI  - HER-2/neu amplification detected by fluorescence in situ hybridization in fine
      needle aspirates from primary breast cancer.
AB  - BACKGROUND: The HER-2/neu gene is amplified in 20-30% of human breast cancers and
      has been shown to have prognostic and predictive value for treatment with
      chemotherapy, hormone therapy and antibodies against the HER-2/neu domain
      (trastuzumab). The aim of our study was to evaluate the reliability of HER-2/neu
      determination by fluorescence in situ hybridization (FISH) on fine-needle
      aspirates (FNAs) from primary breast cancer patients by comparison with the
      results obtained by FISH and immunohistochemistry (IHC) on the corresponding
      histological sections. MATERIALS AND METHODS: HER-2/neu amplification was
      determined by FISH on 66 breast cancer FNAs. Twenty-three and 36 corresponding
      formalin-fixed, paraffin-embedded sections were assayed by FISH and by IHC,
      respectively, in order to detect HER-2/neu amplification and HER-2/neu protein
      expression. RESULTS: Twenty-seven per cent (18/66) of breast cancer FNAs showed
      amplification of HER-2/neu by FISH. Paired results by FISH cytology and FISH
      histology were available in 22 cases. Concordance was 91% (20/22). Paired results
      by FISH cytology and IHC were available in 36 cases. Concordance was 92% (33/36).
      Eighteen of 66 breast cancer FNAs were also submitted to flow cytometric DNA
      analysis. None of the diploid cases showed HER-2/neu amplification by FISH. Six
      out of the eight aneuploid cases were amplified and two were polysomic.
      CONCLUSIONS: HER-2/neu gene amplification can be reliably estimated by FISH on
      breast cancer FNAs and a good correlation has been found between FISH and IHC
      results from the corresponding histological sections.

PMID- 12196366
TI  - Predictive factors for local recurrence in 2006 patients with surgically resected
      small breast cancer.
AB  - BACKGROUND: Analyses of predictive factors for local recurrences are important,
      as an increasing number of patients with early breast cancer opt for a breast
      conserving procedure. This study investigates whether factors predictive of local
      recurrence differ between patients treated with conservative or radical surgery.
      PATIENTS AND METHODS: Two thousands and six patients with invasive breast
      carcinoma (< or =25 mm) were included. Of these patients, 717 were treated
      conservatively (lumpectomy and breast irradiation) and 1289 were treated with
      total mastectomy. All patients had axillary dissection and received lymph node
      irradiation if axillary nodes were positive. Most patients did not receive
      adjuvant chemotherapy or additive hormonal treatments. The mean duration of
      follow-up was 20 years. The main end point was the total local recurrence rate.
      The risk factors of local recurrence were estimated by multivariate analyses and
      interaction tests were used for intergroup comparisons. RESULTS: Statistically
      significant predictive factors for mastectomized patients were histological
      grade, extensive axillary node involvement (10 nodes or more), and inner quadrant
      tumors, which were of borderline significance. Young age, however, was not a
      prognostic indicator for local recurrence. The main statistically significant
      factor for patients treated with a conservative approach was young age (< or =40
      years). These younger patients had a five-fold increased risk of developing a
      breast recurrence compared with patients older than 60 years. CONCLUSIONS:
      Younger patients with early breast cancer treated with breast-conserving surgery
      should in particular be followed up at regular intervals so that any sign of
      local failure can be diagnosed early.

PMID- 12196367
TI  - Informing breast cancer patients about clinical trials: a randomized clinical
      trial of an educational booklet.
AB  - BACKGROUND: To evaluate the impact of an educational booklet on women's knowledge
      of and willingness to participate in a randomized clinical trial of treatment for
      breast cancer. MATERIALS AND METHODS: Women undergoing surgery for newly
      diagnosed early stage breast cancer were randomized to receive, or not, an
      information booklet explaining the need for and manner in which randomized trials
      are conducted. RESULTS: Eighty-three women with newly diagnosed early stage
      breast cancer completed a questionnaire assessing attitudes to random clinical
      trials (RCTs) and were randomized to receive usual information treatment options
      provided from their oncologist, or the educational booklet in addition to usual
      information from their oncologist (42 usual information, 41 booklet). Fewer women
      who received the clinical trials booklet (40% versus 47%) would consider
      participating in the hypothetical clinical trial (P = 0.6). Mean knowledge scores
      increased for both groups; moreover, women who did not receive the booklet showed
      similar improvements to women who received the booklet [mean difference 0.09, 95%
      confidence interval (CI) -0.66 to 0.83]. In a multivariate analysis women who
      would consider participating in the clinical trial were more anxious [odds ratio
      (OR) 5.9, P = 0.02] had involved lymph nodes (OR 5.8, P = 0.02) and were less
      influenced by negative aspects of clinical trials (OR 7.7, P = 0.0001). After
      adjustment for these variables women who received the educational booklet were
      significantly less likely to consider trial participation (OR 0.22, P = 0.05).
      CONCLUSIONS: Educating women about clinical trials in this manner appears
      ineffective in improving recruitment to RCTs. Women appear to be more influenced
      by their perception of risk than understanding. This finding has ethical
      implications for communication of information about RCTs.

PMID- 12196368
TI  - Irinotecan and raltitrexed: an active combination in advanced colorectal cancer.
AB  - BACKGROUND: Irinotecan and raltitrexed are active agents in metastatic colorectal
      cancer. Preclinical findings suggest a remarkable synergistic activity between
      the two drugs and the feasibility of this association has been shown in a recent
      phase I study. The aim of our phase II trial was to assess the efficacy and
      tolerability of the combination of irinotecan and raltitrexed in patients with
      metastatic colorectal cancer untreated with chemotherapy. PATIENTS AND METHODS:
      From June 1998 to February 2000, 46 patients were enrolled. Patients received
      irinotecan 350 mg/m(2) on day 1 and raltitrexed 2.6 mg/m(2) on day 2, every 3
      weeks, for up to nine courses. Tumour assessment was performed every three
      cycles. RESULTS: A total of 223 cycles of chemotherapy, with a median number of
      six (range 1-9) courses per patient, was administered. According to intention-to
      treat analysis, the overall response rate was 46% (95% confidence interval 31% to
      61%). The median duration of response was 21 weeks (range 11-> or =101), the
      median time to progression 27 weeks (range 1-> or =116), and the median overall
      survival 57 weeks (range 1-> or =130). The main toxicities were diarrhoea, with
      National Cancer Institute common toxicity criteria grade 3/4 in 26% of patients,
      grade 3/4 neutropenia in 20%, grade 3 nausea-vomiting in 13%, grade 3 asthenia in
      11% and grade 3/4 transaminase elevation in 4%. CONCLUSIONS: Results achieved
      with irinotecan and raltitrexed show that this regimen is active, despite 'not
      negligible' toxicity, and may represent a useful regimen for specific subgroups
      of colorectal cancer patients.

PMID- 12196369
TI  - Tumour markers as early predictors of response to chemotherapy in advanced
      colorectal carcinoma.
AB  - BACKGROUND: To evaluate the reliability and validity of serum carcinoembryonic
      antigen (CEA), tissue polypeptide-specific antigen (TPS), vascular endothelial
      growth factor (VEGF) and basic fibroblast growth factor (bFGF) in monitoring
      palliative chemotherapy in advanced colorectal cancer (ACRC). METHODS: Serum was
      prospectively collected from 87 patients with ACRC treated with first-line 5
      fluorouracil and leucovorin before and 2, 4 and 10 weeks after induction.
      RESULTS: Eight patients had normal baseline TPS levels, and these patients had a
      favourable outcome with prolonged survival and a higher rate of objective
      responses than patients with elevated TPS levels. At 10 weeks, all responders had
      a decreasing TPS value. The sensitivity for a decrease of >25% using TPS was 83%
      and 86% for objective and subjective responses, respectively, and the specificity
      was 65% and 72%, respectively. CEA had, in the same setting, a sensitivity of 45%
      and 46%, respectively, and the specificity was 88%. VEGF was elevated in 54% of
      the patients and bFGF in 15% of the patients. The VEGF values decreased during
      therapy in 94% of the patients, but the changes in serial VEGF values did not
      correlate with survival or response. Tumour markers used together did not enhance
      the predictive values of TPS alone. CONCLUSIONS: Repeated measurements of CEA,
      VEGF and bFGF in serum are of limited value in monitoring chemotherapy in ACRC.
      TPS seems to be of greater interest, but does not predict exactly which patients
      are going to have a positive outcome of palliative chemotherapy.

PMID- 12196370
TI  - Specific codon 13 K-ras mutations are predictive of clinical outcome in
      colorectal cancer patients, whereas codon 12 K-ras mutations are associated with
      mucinous histotype.
AB  - BACKGROUND: K-ras mutations, one of the earliest events observed in colorectal
      carcinogenesis, are mostly found in codons 12 and 13, and less frequently in
      codon 61, all three of which are estimated to be critical for the biological
      activity of the protein. Nevertheless the prognostic significance of such
      mutations remains controversial. Our purpose was to assess whether any or
      specific K-ras mutations in primary colorectal cancer had prognostic significance
      and were linked to clinico-pathological parameters. PATIENTS AND METHODS: Paired
      tumor and normal tissue samples from a consecutive series of 160 untreated
      patients (median of follow up 71 months), undergoing resective surgery for
      primary colorectal carcinoma, were prospectively studied for K-ras mutations by
      PCR/single strand conformation polymorphism sequencing. RESULTS: Seventy-four of
      the 160 (46%) primary colorectal carcinomas presented mutations in K-ras: 54% in
      codon 12, 42% in codon 13 (particularly G-->A transition) and 4% in both. Codon
      12 K-ras mutations were associated with mucinous histotype (P <0.01), while codon
      13 K-ras mutations were associated with advanced Dukes' stage (P <0.05), lymph
      node metastasis (P <0.05) and high S-phase fraction (P <0.05). Multivariate
      analysis showed that codon 13 K-ras mutations, but not any mutation, were
      independently related to risk of relapse or death. CONCLUSIONS: Our results
      suggest that codon 12 K-ras mutations may have a role in the mucinous
      differentiation pathway, while codon 13 mutations have biological relevance in
      terms of colorectal cancer clinical outcome.

PMID- 12196371
TI  - Prevalence and prognostic role of microsatellite instability in patients with
      rectal carcinoma.
AB  - BACKGROUND: Association between microsatellite instability (MSI) and favorable
      postoperative survival in patients with colorectal cancer receiving adjuvant
      chemotherapy has been indicated. To evaluate whether an analogous positive
      prognostic role of MSI could be present in rectal carcinoma (RC; most RC patients
      receive adjuvant radiotherapy), PCR-based microsatellite analysis of archival RCs
      and statistical correlation with clinico-pathological parameters were performed.
      PATIENTS AND METHODS: DNA from paraffin-embedded paired samples of tumors and
      corresponding normal tissue from 91 RC patients was analyzed for MSI using five
      microsatellite markers (tumors were classified as MSI(+) when two or more markers
      were unstable). RESULTS: Seventeen (19%) RC patients exhibited a MSI(+)
      phenotype. Prevalence of instability was found in patients with earlier RC onset
      (28% in cases with diagnosis age < or =55 years versus 15% in cases >55 years),
      whereas similar MSI frequencies were observed in patients with different disease
      stage or receiving different adjuvant therapies. While MSI was detected in seven
      (64%) of 11 familial patients, a remarkably lower MSI incidence was observed in
      sporadic cases (10/80; 12.5%). A significant association with better disease-free
      survival (DFS) and overall survival (OS) was found for MSI(+) patients (median
      DFS/OS, 30/32 months) in comparison to MSI(-) ones (median DFS/OS, 18/21 months)
      (P <0.001). CONCLUSIONS: MSI was demonstrated to be a strong molecular prognostic
      marker in rectal carcinoma, independent of the administered treatment
      (radiotherapy, chemotherapy or both).

PMID- 12196372
TI  - A phase II randomised trial comparing the cisplatin-etoposide combination
      chemotherapy with or without carboplatin as second-line therapy for small-cell
      lung cancer.
AB  - BACKGROUND: A phase II randomised trial was performed with patients with SCLC to
      determine if the addition of carboplatin to cisplatin-etoposide might improve the
      response rate in second-line therapy. PATIENTS AND METHODS: Sixty-five eligible
      patients were randomised: 31 for CE (cisplatin 20 mg/m(2) and etoposide 100
      mg/m(2) on days 1-3) and 34 for CCE (carboplatin 200 mg/m(2) on day 1, cisplatin
      30 mg/m(2) on days 2-3, etoposide 100 mg/m(2) on days 1-3). RESULTS: Eighty-two
      per cent of these patients had an objective response to first-line therapy and,
      among responders, 63% had a treatment-free interval of >3 months after previous
      therapy. The best response rates were 29% [95% confidence interval (CI) 13-45]
      and 47% (95% CI 30-64) for CE and CCE, respectively, with median survival times
      of 4.3 and 7.6 months. Dose-intensity analysis revealed a significant improvement
      in the relative dose-intensity and etoposide absolute dose-intensity for CE.
      Toxicity was tolerable and comparable between the two study arms. CONCLUSION: CCE
      appears to be associated with a high objective response rate. The phase II
      randomised study design suggests that a comparison between the two regimens in a
      phase III trial would be interesting, but will probably be difficult to perform
      for reasons of accrual.

PMID- 12196373
TI  - Prognostic factors of survival and rapid progression in 782 patients with
      metastatic renal carcinomas treated by cytokines: a report from the Groupe
      Francais d'Immunotherapie.
AB  - Interleukin-2 (IL-2) or/and interferon (IFN) are routinely used for treating
      patients with metastatic renal cell cancer. However, results have been
      disappointing, with a majority of treatment failure. Over 6 years, the Groupe
      Francais d'Immunotherapie enrolled 782 patients in successive multicenter trials
      using cytokine regimens. Univariate and multivariate analyses were performed on
      this large prospective database to identify prognostic factors for survival. The
      presence of biological signs of inflammation, short time interval from renal
      tumor to metastases (<1 year), elevated neutrophil counts, liver metastases, bone
      metastases, patient performance status (PS), the number of metastatic sites,
      alkaline phosphatases and hemoglobin levels were predictive of survival outcome.
      When compared with previous results, our study showed that PS, number of
      metastatic sites, disease-free interval, biological signs of inflammation and
      hemoglobin levels can be considered as validated prognostic factors. We also
      identified four independent factors predictive of rapid progression under
      cytokine treatment: presence of hepatic metastases, short interval from renal
      tumor to metastases (<1 year), more than one metastatic site and elevated
      neutrophil counts. Patients who combined at least three of these factors have
      >80% probability of rapid progression despite treatment. We think that these
      results must be taken into account when making the decision to treat with
      cytokine.

PMID- 12196374
TI  - A phase I and pharmacokinetic study of capecitabine in combination with
      epirubicin and cisplatin in patients with inoperable oesophago-gastric
      adenocarcinoma.
AB  - BACKGROUND: The purpose of this study was to evaluate the dose-limiting toxicity
      (DLT) and maximum tolerated dose of capecitabine when used in combination with
      epirubicin and cisplatin (ECC) in patients with oesophageal or gastric
      adenocarcinoma. Response rate, progression-free survival (PFS) and overall
      survival were also determined, and the effect of previous oesophago-gastric
      surgery or concurrent oesophago-gastric cancer on the absorption and metabolism
      of capecitabine was evaluated. PATIENTS AND METHODS: Patients with inoperable
      oesophago-gastric adenocarcinoma received up to six cycles of epirubicin (50
      mg/m(2) i.v., 3-weekly), cisplatin (60 mg/m(2) i.v., 3-weekly) and capecitabine,
      the latter administered orally in an intermittent schedule (14 days treatment; 7
      day rest period) at 3-weekly intervals. Patients were recruited into one of four
      escalating dose cohorts (500, 825, 1000 and 1250 mg/m(2) bd). Dose escalation
      occurred after six patients had completed at least one cycle of chemotherapy at
      the previous dose level, with DLT assessed on the toxicity of the first cycle
      only. Blood sampling for pharmacokinetic analyses was performed over the first 10
      h of day 1 of cycle 1. RESULTS: Thirty-two patients, median age 63 years (range
      32-76 years), ECOG performance status < or =2 with locally advanced (10) or
      metastatic (22) disease were recruited and were evaluable for toxicity. Two of
      five patients experienced DLT at 1250 mg/m(2) bd with grade II stomatitis (one
      patient) and grade III diarrhoea with febrile neutropenia (one patient).
      Cumulative toxicity for all cycles (n = 140) (worst grade per patient) includes
      grade IV oesophagitis (one patient), grade III diarrhoea (five), grade IV
      neutropenia with infection (seven), grade II stomatitis (four) and grade IV
      thrombocytopenia (one). Of 29 patients with evaluable disease, there was one
      complete response and six partial responses [24% response rate [95% confidence
      interval (CI) 10% to 44%]], a median PFS of 22 weeks (95% CI 17-27 weeks) and
      median overall survival of 34 weeks (95% CI 19-49 weeks). Capecitabine was
      rapidly absorbed after oral administration, with a t(max) of 1-2 h for
      capecitabine, DFCR (5'-deoxy-5-fluorocytidine) and DFUR (5'-deoxy-5
      fluorouridine). The C(max) and AUC(0-)( infinity ) for capecitabine, DFCR and
      DFUR were similar to those observed in previous monotherapy studies of
      capecitabine taken after food. CONCLUSION: A dose of 1000 mg/m(2) bd of
      capecitabine is recommended for use on an intermittent schedule in combination
      with these doses and schedule of epirubicin and cisplatin. This regimen is
      tolerable and active in oesophago-gastric adenocarcinoma. A randomised phase III
      comparison with ECF is justified.

PMID- 12196375
TI  - Phase I-II and pharmacokinetic study of gemcitabine combined with oxaliplatin in
      patients with advanced non-small-cell lung cancer and ovarian carcinoma.
AB  - BACKGROUND: The aim of this study was to determine the toxicity profile, the
      recommended dose (RD) and the pharmacokinetic parameters, and to evaluate the
      antitumor activity of gemcitabine combined with oxaliplatin in patients with
      advanced non-small-cell lung cancer (NSCLC) and ovarian carcinoma (OC). METHODS:
      Gemcitabine was administered as a 30-min infusion followed by a 2-h infusion of
      oxaliplatin, repeated every 2 weeks. Doses of gemcitabine and oxaliplatin ranged
      from 800 to 1500 and 70 to 100 mg/m(2), respectively. RESULTS: Forty-four
      patients (26 males, 18 females; median age 55 years) including 35 NSCLC (five
      platinum pretreated) and nine OC patients (all platinum pretreated) received a
      total of 355 cycles. All patients were evaluable for toxicity. No dose-limiting
      toxicity at any dose level occurred during the first two cycles; therefore, the
      highest dose-level of gemcitabine (1500 mg/m(2)) and oxaliplatin (85 mg/m(2)) was
      considered as the RD. Hematological toxicity was moderate amongst the 22 patients
      treated (167 cycles) at that dose level. Thirteen cycles were associated with
      grade 3-4 non-febrile neutropenia in six patients, and eight cycles with grade 3
      4 thrombocytopenia in two patients. Other toxicities were mild to moderate,
      consisting of asthenia and peripheral neurotoxicity. Four of the 35 patients
      treated with oxaliplatin 85 mg/m(2) experienced grade 3 neurotoxicity requiring
      treatment discontinuation at cycle 10. In the range of the doses used,
      gemcitabine and its main metabolite 2',2'-difluorodeoxyuridine appeared not to be
      affected by oxaliplatin 70-100 mg/m(2). Of the 44 patients evaluable for
      activity, 12 NSCLC patients experienced objective responses (one complete and 11
      partial responses) and three OC patients showed tumor stabilization lasting for 6
      months with a 50% decrease of CA 125 level. Two partial responses (NSCLC) and one
      tumor stabilization (OC) occurred in platinum-resistant patients. CONCLUSIONS:
      The combination of gemcitabine and oxaliplatin could be safely administered on an
      out-patient schedule in patients with advanced NSCLC and OC. The RD was
      gemcitabine 1500 mg/m(2) and oxaliplatin 85 mg/m(2) every 2 weeks. Promising
      antitumor activity was reported in patients with NSCLC and platinum-pretreated
      OC, and thus, deserves further evaluation.

PMID- 12196376
TI  - Phase I study of weekly oxaliplatin plus irinotecan in previously treated
      patients with metastatic colorectal cancer.
AB  - BACKGROUND: In vitro synergy between Oxal (oxaliplatin) and CPT-11 (irinotecan)
      has been reported. Oxaliplatin exerts its antineoplastic activity through the
      formation of platinum-DNA adducts. Resistance to oxaliplatin is through repair of
      these adducts, which is inhibited by irinotecan. PATIENTS AND METHODS:
      Oxaliplatin and irinotecan were administered weekly for 4 weeks followed by a 2
      week rest period. The dose of oxaliplatin was escalated first, starting at 30
      mg/m(2). Once a dose of 60 mg/m(2) was attained, the weekly dose of irinotecan
      was escalated, from 40 mg/m(2) to 85 mg/m(2). A total of 49 previously treated
      patients with metastatic colorectal cancer were entered in order to establish the
      maximum tolerated dose. Pharmacokinetics of oxaliplatin and irinotecan were
      analyzed. RESULTS: Forty-nine patients were evaluable for toxicity. The
      recommended phase II doses for this combination are oxaliplatin 60 mg/m(2) and
      irinotecan 50 mg/m(2), weekly x 4 q 6 weeks. Diarrhea was the most common dose
      limiting toxicity. No pharmacological interactions were noted between oxaliplatin
      and irinotecan. Twelve of the 47 evaluable patients (26%) achieved a partial
      response. CONCLUSION: Weekly combination of oxaliplatin and irinotecan appears to
      be a well tolerated and active regimen in patients previously treated for
      metastatic colorectal cancer. Further investigations of this regimen are
      warranted.

PMID- 12196378
TI  - Intravascular large B-cell lymphoma with a fulminant clinical course: a case
      report with definite diagnosis post mortem.
AB  - A patient is described who presented with pancytopenia, splenomegaly and
      excessively elevated lactate dehydrogenase levels in concurrence with signs of
      extramedullary hematopoiesis. Although initially considered in the differential
      diagnostic spectrum, a highly aggressive lymphoma could not be identified before
      the patient died, 6 weeks after admission. Even an intensive diagnostic work-up
      including splenectomy and repeated bone marrow biopsies was inconclusive.
      Finally, the diagnosis of an intravascular large B-cell lymphoma, a highly
      aggressive clinical subtype of a diffuse large B-cell lymphoma, spreading within
      vascular structures of multiple organs was established by autopsy. Intravascular
      large B-cell lymphoma is often not diagnosed before death due to the exclusive
      intravascular growth pattern of the tumor cells and a fulminant clinical course.
      The heterogeneous clinical features of this lymphoma subtype are discussed.

PMID- 12196377
TI  - Fighting colorectal cancer: molecular epidemiology differences among Ashkenazi
      and Sephardic Jews and Palestinians.
AB  - BACKGROUND: To evaluate and compare differences in the molecular genetics among
      high-risk (Ashkenazi Jews), intermediate-risk (Sephardic Jews) and low-risk
      (Palestinians) groups for colorectal cancer who live in the same geographical
      region. PATIENTS AND METHODS: The 1995-1996 records from the Tel Aviv Medical
      Center and Muqased hospital (East Jerusalem) randomly identified patients with
      colorectal cancer. There were 25 patients from each ethnic group. Epidemiological
      data were obtained from interviews with the patients and from their hospital
      charts. The levels of cyclin D1, beta-catenine, p27, p53, Ki-67 and Her-2/neu
      proteins were determined by immunohistochemistry. The main outcome measures were
      the association between gene expression and colorectal incidence in the different
      ethnic groups. RESULTS: Ashkenazi Jews have the highest rate of colorectal
      cancer, and are diagnosed at an early stage compared with Palestinians (72% and
      33% of the cases are in Dukes' A and B, respectively), and, hence, this may
      explain the better 5-year survival rate among this group. Sephardic Jews are
      diagnosed at a more advanced stage, the tumors are poorly differentiated and they
      lack p27. Palestinians have significantly higher cyclin D1 levels. There was a
      statistically significant inverse correlation between the expression of beta
      catenine and cyclin D1, as well as p53 and p27 (P <0.05). CONCLUSIONS: Increased
      expression of cyclin D1, p53, Ki-67, beta-catenine and Her-2/neu, and decreased
      expression of p27 may be important events in the three ethnic groups with
      colorectal cancer. The lower mortality rate among Ashkenazi Jews may be partially
      explained by their better molecular biology profile.

PMID- 12196379
TI  - Critical appraisal of the Minimal Clinical Recommendations (MCR) of the European
      Society for Medical Oncology (ESMO): challenges for a European framework for the
      development of clinical practice guidelines.

PMID- 12196382
TI  - Allogeneic stem cell transplantation for patients with resistant high-grade
      lymphoma: what is the potential of reduced-intensity conditioning?

PMID- 12196384
TI  - A biological perspective on the selection of stage II colorectal cancer patients
      for adjuvant chemotherapy.

PMID- 12196385
TI  - C. C. Little, cancer and inbred mice.

PMID- 12196386
TI  - Saturation of DNA mismatch repair and error catastrophe by a base analogue in
      Escherichia coli.
AB  - Deoxyribosyl-dihydropyrimido[4,5-c][1,2]oxazin-7-one (dP) is a potent mutagenic
      deoxycytidine-derived base analogue capable of pairing with both A and G, thereby
      causing G. C --> A. T and A. T --> G. C transition mutations. We have found that
      the Escherichia coli DNA mismatch-repair system can protect cells against this
      mutagenic action. At a low dose, dP is much more mutagenic in mismatch-repair
      defective mutH, mutL, and mutS strains than in a wild-type strain. At higher
      doses, the difference between the wild-type and the mutator strains becomes
      small, indicative of saturation of mismatch repair. Introduction of a plasmid
      containing the E. coli mutL(+) gene significantly reduces dP-induced mutagenesis.
      Together, the results indicate that the mismatch-repair system can remove dP
      induced replication errors, but that its capacity to remove dP-containing
      mismatches can readily be saturated. When cells are cultured at high dP
      concentration, mutant frequencies reach exceptionally high levels and viable cell
      counts are reduced. The observations are consistent with a hypothesis in which dP
      induced cell killing and growth impairment result from excess mutations (error
      catastrophe), as previously observed spontaneously in proofreading-deficient mutD
      (dnaQ) strains.

PMID- 12196387
TI  - Genomic changes in nucleotide and dinucleotide frequencies in Pasteurella
      multocida cultured under high temperature.
AB  - We used 94 RAPD primers of different nucleotide composition to probe the genomic
      differences between a highly virulent P. multocida strain and an attenuated
      vaccine strain derived from the virulent strain after culturing the latter under
      increasing temperature for approximately 14,400 generations. The GC content of
      the vaccine strain is significantly (P < 0.05) lower than that of the virulent
      strain, contrary to the popular hypothesis of covariation between the GC content
      and temperature. The frequencies of AA, TA, and TT dinucleotides were higher, and
      those of AT, GC, and CG dinucleotides were lower, in the vaccine strain than in
      the virulent strain. A statistic called genomic RAPD entropy is formulated to
      measure the randomness of the genome, and the genome of the vaccine strain is
      more random than that of the virulent strain. These differences between the
      virulent and vaccine strains are interpreted in terms of mutation and selection
      under increased culturing temperature. A method for estimating substitution rates
      is developed in the appendix.

PMID- 12196388
TI  - The tRNA-Tyr gene family of Saccharomyces cerevisiae: agents of phenotypic
      variation and position effects on mutation frequency.
AB  - Extensive phenotypic diversity or variation exists in clonal populations of
      microorganisms and is thought to play a role in adaptation to novel environments.
      This phenotypic variation or instability, which occurs by multiple mechanisms,
      may be a form of cellular differentiation and a stochastic means for modulating
      gene expression. This work dissects a case of phenotypic variation in a
      clinically derived Saccharomyces cerevisiae strain involving a cox15 ochre
      mutation, which acts as a reporter. The ochre mutation reverts to sense at a low
      frequency while tRNA-Tyr ochre suppressors (SUP-o) arise at a very high frequency
      to produce this phenotypic variation. The SUP-o mutations are highly pleiotropic.
      In addition, although all SUP-o mutations within the eight-member tRNA-Tyr gene
      family suppress the ochre mutation reporter, there are considerable phenotypic
      differences among the different SUP-o mutants. Finally, and of particular
      interest, there is a strong position effect on mutation frequency within the
      eight-member tRNA-Tyr gene family, with one locus, SUP6, mutating at a much
      higher than average frequency and two other loci, SUP2 and SUP8, mutating at much
      lower than average frequencies. Mechanisms for the position effect on mutation
      frequency are evaluated.

PMID- 12196389
TI  - A role for the Saccharomyces cerevisiae RENT complex protein Net1 in HMR
      silencing.
AB  - Silencing in the yeast Saccharomyces cerevisiae is known in three classes of
      loci: in the silent mating-type loci HML and HMR, in subtelomeric regions, and in
      the highly repetitive rDNA locus, which resides in the nucleolus. rDNA silencing
      differs markedly from the other two classes of silencing in that it requires a
      DNA-associated protein complex termed RENT. The Net1 protein, a central component
      of RENT, is required for nucleolar integrity and the control of exit from
      mitosis. Another RENT component is the NAD(+)-dependent histone deacetylase Sir2,
      which is the only silencing factor known to be shared among the three classes of
      silencing. Here, we investigated the role of Net1 in HMR silencing. The mutation
      net1-1, as well as NET1 expression from a 2micro-plasmid, restored repression at
      silencing-defective HMR loci. Both effects were strictly dependent on the Sir
      proteins. We found overexpressed Net1 protein to be directly associated with the
      HMR-E silencer, suggesting that Net1 could interact with silencer binding
      proteins and recruit other silencing factors to the silencer. In agreement with
      this, Net1 provided ORC-dependent, Sir1-independent silencing when artificially
      tethered to the silencer. In contrast, our data suggested that net1-1 acted
      indirectly in HMR silencing by releasing Sir2 from the nucleolus, thus shifting
      the internal competition for Sir2 from the silenced loci toward HMR.

PMID- 12196390
TI  - A heritable structural alteration of the yeast mitochondrion.
AB  - Prions have revived interest in hereditary change that is due to change in
      cellular structure. How pervasive is structural inheritance and what are its
      mechanisms? Described here is the initial characterization of [Leu(P)], a
      heritable structural change of the mitochondrion of Saccharomyces cerevisiae that
      often but not always accompanies the loss of all or part of the mitochondrial
      genome. Three phenotypes are reported in [Leu(P)] vs. [Leu(+)] strains: twofold
      slower growth, threefold slower growth in the absence of leucine, and a marked
      delocalization of nuclear-encoded protein destined for the mitochondrion.
      Introduction of mitochondria from a [Leu(+)] strain by cytoduction can convert a
      [Leu(P)] strain to [Leu(+)] and vice versa. Evidence against the Mendelian
      inheritance of the trait is presented. The incomplete dominance of [Leu(P)] and
      [Leu(+)] and the failure of HSP104 deletion to have any effect suggest that the
      trait is not specified by a prion but instead represents a new class of heritable
      structural change.

PMID- 12196391
TI  - Telomere binding of checkpoint sensor and DNA repair proteins contributes to
      maintenance of functional fission yeast telomeres.
AB  - Telomeres, the ends of linear chromosomes, are DNA double-strand ends that do not
      trigger a cell cycle arrest and yet require checkpoint and DNA repair proteins
      for maintenance. Genetic and biochemical studies in the fission yeast
      Schizosaccharomyces pombe were undertaken to understand how checkpoint and DNA
      repair proteins contribute to telomere maintenance. On the basis of telomere
      lengths of mutant combinations of various checkpoint-related proteins (Rad1,
      Rad3, Rad9, Rad17, Rad26, Hus1, Crb2, Chk1, Cds1), Tel1, a telomere-binding
      protein (Taz1), and DNA repair proteins (Ku70, Rad32), we conclude that
      Rad3/Rad26 and Tel1/Rad32 represent two pathways required to maintain telomeres
      and prevent chromosome circularization. Rad1/Rad9/Hus1/Rad17 and Ku70 are two
      additional epistasis groups, which act in the Rad3/Rad26 pathway. However,
      Rad3/Rad26 must have additional target(s), as cells lacking Tel1/Rad32,
      Rad1/Rad9/Hus1/Rad17, and Ku70 groups did not circularize chromosomes. Cells
      lacking Rad3/Rad26 and Tel1/Rad32 senesced faster than a telomerase trt1Delta
      mutant, suggesting that these pathways may contribute to telomere protection.
      Deletion of taz1 did not suppress chromosome circularization in cells lacking
      Rad3/Rad26 and Tel1/Rad32, also suggesting that two pathways protect telomeres.
      Chromatin immunoprecipitation analyses found that Rad3, Rad1, Rad9, Hus1, Rad17,
      Rad32, and Ku70 associate with telomeres. Thus, checkpoint sensor and DNA repair
      proteins contribute to telomere maintenance and protection through their
      association with telomeres.

PMID- 12196392
TI  - Loss of ypk1 function causes rapamycin sensitivity, inhibition of translation
      initiation and synthetic lethality in 14-3-3-deficient yeast.
AB  - 14-3-3 proteins bind to phosphorylated proteins and regulate a variety of
      cellular activities as effectors of serine/threonine phosphorylation. To define
      processes requiring 14-3-3 function in yeast, mutants with increased sensitivity
      to reduced 14-3-3 protein levels were identified by synthetic lethal screening.
      One mutation was found to be allelic to YPK1, which encodes a Ser/Thr protein
      kinase. Loss of Ypk function causes hypersensitivity to rapamycin, similar to 14
      3-3 mutations and other mutations affecting the TOR signaling pathway in yeast.
      Similar to treatment with rapamycin, loss of Ypk function disrupted translation,
      at least in part by causing depletion of eIF4G, a central adaptor protein
      required for cap-dependent mRNA translation initiation. In addition, Ypk1 as well
      as eIF4G protein levels were rapidly depleted upon nitrogen starvation, but not
      during glucose starvation, even though both conditions inhibit translation
      initiation. These results suggest that Ypk regulates translation initiation in
      response to nutrient signals, either through the TOR pathway or in a functionally
      related pathway parallel to TOR.

PMID- 12196394
TI  - Meiotic silencing by unpaired DNA: properties, regulation and suppression.
AB  - In Neurospora, a gene not paired with a homolog in prophase I of meiosis
      generates a signal that transiently silences all sequences homologous to it by a
      process called meiotic silencing by unpaired DNA (MSUD). Thus a deletion mutation
      in a heterozygous cross is formally "ascus-dominant" because its unpaired wild
      type partner silences itself. We describe in detail the isolation of a mutation,
      Sad-1(UV), that suppresses the dominance of various ascus-dominant mutations.
      Additional dominant, semidominant, and recessive Sad-1 alleles have been
      generated by RIP; the DNA of the dominant RIP alleles becomes methylated, but dim
      2-dependent methylation is not necessary for silencing. The barrenness of
      homozygous Sad-1 crosses is not due to the failure to silence unpaired mating
      type mat A-2 mat A-3 genes. Transcripts of sad-1(+) can be detected during the
      sexual phase in a homozygous wild-type cross, indicating that the gene is
      expressed even if all DNA can pair normally. Meiotic silencing is confined to the
      ascus in which DNA is unpaired, and silencing does not spread to neighboring asci
      in a fruiting body of mixed genetic constitution.

PMID- 12196393
TI  - Nuclear import of Upf3p is mediated by importin-alpha/-beta and export to the
      cytoplasm is required for a functional nonsense-mediated mRNA decay pathway in
      yeast.
AB  - Upf3p, which is required for nonsense-mediated mRNA decay (NMD) in yeast, is
      primarily cytoplasmic but accumulates inside the nucleus when UPF3 is
      overexpressed or when upf3 mutations prevent nuclear export. Upf3p physically
      interacts with Srp1p (importin-alpha). Upf3p fails to be imported into the
      nucleus in a temperature-sensitive srp1-31 strain, indicating that nuclear import
      is mediated by the importin-alpha/beta heterodimer. Nuclear export of Upf3p is
      mediated by a leucine-rich nuclear export sequence (NES-A), but export is not
      dependent on the Crm1p exportin. Mutations identified in NES-A prevent nuclear
      export and confer an Nmd(-) phenotype. The addition of a functional NES element
      to an export-defective upf(-) allele restores export and partially restores an
      Nmd(+) phenotype. Our findings support a model in which the movement of Upf3p
      between the nucleus and the cytoplasm is required for a fully functional NMD
      pathway. We also found that overexpression of Upf2p suppresses the Nmd(-)
      phenotype in mutant strains carrying nes-A alleles but has no effect on the
      localization of Upf3p. To explain these results, we suggest that the mutations in
      NES-A that impair nuclear export cause additional defects in the function of
      Upf3p that are not rectified by restoration of export alone.

PMID- 12196395
TI  - A combined amplified fragment length polymorphism and randomly amplified
      polymorphism DNA genetic kinkage map of Mycosphaerella graminicola, the septoria
      tritici leaf blotch pathogen of wheat.
AB  - An F(1) mapping population of the septoria tritici blotch pathogen of wheat,
      Mycosphaerella graminicola, was generated by crossing the two Dutch field
      isolates IPO323 and IPO94269. AFLP and RAPD marker data sets were combined to
      produce a high-density genetic linkage map. The final map contained 223 AFLP and
      57 RAPD markers, plus the biological traits mating type and avirulence, in 23
      linkage groups spanning 1216 cM. Many AFLPs and some RAPD markers were clustered.
      When markers were reduced to 1 per cluster, 229 unique positions were mapped,
      with an average distance of 5.3 cM between markers. Because M. graminicola
      probably has 17 or 18 chromosomes, at least 5 of the 23 linkage groups probably
      will need to be combined with others once additional markers are added to the
      map. This was confirmed by pulsed-field gel analysis; probes derived from 2 of
      the smallest linkage groups hybridized to two of the largest chromosome-sized
      bands, revealing a discrepancy between physical and genetic distance. The utility
      of the map was demonstrated by identifying molecular markers tightly linked to
      two genes of biological interest, mating type and avirulence. Bulked segregant
      analysis was used to identify additional molecular markers closely linked to
      these traits. This is the first genetic linkage map for any species in the genus
      Mycosphaerella or the family Mycosphaerellaceae.

PMID- 12196396
TI  - The DSC1 channel, encoded by the smi60E locus, contributes to odor-guided
      behavior in Drosophila melanogaster.
AB  - Previously, we generated P-element insert lines in Drosophila melanogaster with
      impaired olfactory behavior. One of these smell-impaired (smi) mutants, smi60E,
      contains a P[lArB] transposon in the second intron of the dsc1 gene near a nested
      gene encoding the L41 ribosomal protein. The dsc1 gene encodes an ion channel of
      unknown function homologous to the paralytic (para) sodium channel, which
      mediates neuronal excitability. Complementation tests between the smi60E mutant
      and several EP insert lines map the smell-impaired phenotype to the P[lArB]
      insertion site. Wild-type behavior is restored upon P-element excision. Evidence
      that reduction in DSC1 rather than in L41 expression is responsible for the smell
      impaired phenotype comes from a phenotypic revertant in which imprecise P-element
      excision restores the DSC1 message while further reducing L41 expression.
      Behavioral assays show that a threefold decrease in DSC1 mRNA is accompanied by a
      threefold shift in the dose response for avoidance of the repellent odorant,
      benzaldehyde, toward higher odorant concentrations. In situ hybridization reveals
      widespread expression of the dsc1 gene in the major olfactory organs, the third
      antennal segment and the maxillary palps, and in the CNS. These results indicate
      that the DSC1 channel contributes to processing of olfactory information during
      the olfactory avoidance response.

PMID- 12196397
TI  - Hybrid sterility, Haldane's rule and speciation in Heliconius cydno and H.
      melpomene.
AB  - Most genetic studies of Haldane's rule, in which hybrid sterility or inviability
      affects the heterogametic sex preferentially, have focused on Drosophila. It
      therefore remains unclear to what extent the conclusions of that work apply more
      generally, particularly in female-heterogametic taxa such as birds and
      Lepidoptera. Here we present a genetic analysis of Haldane's rule in Heliconius
      butterflies. Female F(1) hybrids between Heliconius melpomene and H. cydno are
      completely sterile, while males have normal to mildly reduced fertility. In
      backcrosses of male F(1) hybrids, female offspring range from completely sterile
      to fully fertile. Linkage analysis using the Z-linked triose-phosphate isomerase
      locus demonstrates a "large X" (Z) effect on sterility. Expression of female
      sterility varies among crosses in this and a previous study of Heliconius.
      Sterility may result from the production of normal but infertile eggs, production
      of small infertile eggs, or from a complete failure to develop ovarioles, which
      suggests multiple routes to the evolution of hybrid sterility in these Heliconius
      species. These results conform to the expectations of the "dominance" rather than
      "faster male" theories of Haldane's rule and suggest that relatively few loci are
      responsible. The two species are broadly sympatric and hybridize in the wild, so
      that female hybrid sterility forms one of several strong but incomplete barriers
      to gene flow in nature. The effect of female sterility is comparable to that of
      selection against non-mimetic hybrids, while mate choice forms a much stronger
      barrier to gene transfer.

PMID- 12196399
TI  - Distribution of nonrandom associations between pairs of protein loci along the
      third chromosome of Drosophila melanogaster.
AB  - The within-chromosome distribution of gametic disequilibrium (GD) between protein
      loci, and the underlying evolutionary factors of this distribution, are still
      largely unknown. Here, we report a detailed study of GD between a large number of
      protein loci (15) spanning 87% of the total length of the third chromosome of
      Drosophila melanogaster in a large sample of haplotypes (600) drawn from a single
      natural population. We used a sign-based GD estimation method recently developed
      for multiallelic systems, which considerably increases both the statistical power
      and the accuracy of estimation of the intensity of GD. We found that strong GD
      between pairs of protein loci was widespread throughout the chromosome. In total,
      22% of both the pairs of alleles and pairs of loci were in significant GD, with
      mean intensities (as measured by D' coefficients) of 0.43 and 0.31, respectively.
      In addition, strong GD often occurs between loci that are far apart. By way of
      illustration, 32% of the allele pairs in significant GD occurred within pairs of
      loci separated by effective frequencies of recombination (EFRs) of 15-20 cM, the
      mean D' value being 0.49. These observations are in sharp contrast with previous
      studies showing that GD between protein loci is rarely found in natural
      populations of outcrossing species, even between very closely linked loci.
      Interestingly, we found that most instances of significant interallelic GD (68%)
      involved functionally related protein loci. Specifically, GD was markedly more
      frequent between protein loci related by the functions of hormonal control,
      molybdenum control, antioxidant defense system, and reproduction than between
      loci without known functional relationship, which is indicative of epistatic
      selection. Furthermore, long-distance GD between functionally related loci (mean
      EFR 9 cM) suggests that epistatic interactions must be very strong along the
      chromosome. This evidence is hardly compatible with the neutral theory and has
      far-reaching implications for understanding the multilocus architecture of the
      functional genome. Our findings also suggest that GD may be a useful tool for
      discovering networks of functionally interacting proteins.

PMID- 12196398
TI  - The bantam gene regulates Drosophila growth.
AB  - We report here the consequences of mutations of a novel locus, named bantam,
      whose product is involved in the regulation of growth in Drosophila. bantam
      mutant animals are smaller than wild type, due to a reduction in cell number but
      not cell size, and do not have significant disruptions in patterning. Conversely,
      overexpression of the bantam product using the EP element EP(3)3622 causes
      overgrowth of wing and eye tissue. Overexpression in clones of cells results in
      an increased rate of cell proliferation and a matched increase in cellular growth
      rate, such that the resulting tissue is composed of more cells of a size
      comparable to wild type. These effects are strikingly similar to those associated
      with alterations in the activity of the cyclinD-cdk4 complex. However, epistasis
      and genetic interaction analyses indicate that bantam and cyclinD-cdk4 operate
      independently. Thus, the bantam locus represents a novel regulator of tissue
      growth.

PMID- 12196400
TI  - Does Stellate cause meiotic drive in Drosophila melanogaster?
AB  - Drosophila melanogaster males deficient for the crystal (cry) locus of the Y
      chromosome that carry between 15 and 60 copies of the X-linked Stellate (Ste)
      gene are semisterile, have elevated levels of nondisjunction, produce distorted
      sperm genotype ratios (meiotic drive), and evince hyperactive transcription of
      Ste in the testes. Ste seems to be the active element in this system, and it has
      been proposed that the ancestral Ste gene was "selfish" and increased in
      frequency because it caused meiotic drive. This hypothetical evolutionary history
      is based on the idea that Ste overexpression, and not the lack of cry, causes the
      meiotic drive of cry(-) males. To test whether this is true, we have constructed
      a Ste-deleted X chromosome and examined the phenotype of Ste(-)/cry(-) males. If
      hyperactivity of Ste were necessary for the transmission defects seen in cry(-)
      males, cry(-) males completely deficient for Ste would be normal. Although it is
      impossible to construct a completely Ste(-) genotype, we find that Ste(-)/cry(-)
      males have exactly the same phenotype as Ste(+)/cry(-) males. The deletion of all
      X chromosome Ste copies not only does not eliminate meiotic drive and
      nondisjunction, but it also does not even reduce them below the levels produced
      when the X carries 15 copies of Ste.

PMID- 12196401
TI  - Genetic differentiation in the African malaria vector, Anopheles gambiae s.s.,
      and the problem of taxonomic status.
AB  - Of the seven recognized species of the Anopheles gambiae complex, A. gambiae s.s.
      is the most widespread and most important vector of malaria. It is becoming clear
      that, in parts of West Africa, this nominal species is not a single panmictic
      unit. We found that the internal transcribed spacer (ITS) of the X-linked rDNA
      has two distinct sequences with three fixed nucleotide differences; we detected
      no heterozygotes at these three sites, even in areas of sympatry of the two ITS
      types. The intergenic spacer (IGS) of this region also displays two distinct
      sequences that are in almost complete linkage disequilibrium with the distinct
      ITS alleles. We have designated these two types as S/type I and M/type II. These
      rDNA types correspond at least partly to the previously recognized chromosomal
      forms. Here we expand the geographic range of sampling to 251 individuals from 38
      populations. Outside of West Africa, a single rDNA type, S/type I, corresponds to
      the Savanna chromosomal form. In West Africa, both types are often found in a
      single local sample. To understand if these findings might be due to unusual
      behavior of the rDNA region, we sequenced the same region for 46 A. arabiensis, a
      sympatric sibling species. No such distinct discontinuity was observed for this
      species. Autosomal inversions in one chromosome arm (2R), an insecticide
      resistance gene on 2L, and this single X-linked region indicate at least two
      genetically differentiated subpopulations of A. gambiae. Yet, rather extensive
      studies of other regions of the genome have failed to reveal genetic
      discontinuity. Evidently, incomplete genetic isolation exists within this single
      nominal species.

PMID- 12196402
TI  - Genetics of mother-dependent sex ratio in blue mussels (Mytilus spp.) and
      implications for doubly uniparental inheritance of mitochondrial DNA.
AB  - Previous studies have shown that in most pair matings of Mytilus edulis, M.
      trossulus, and M. galloprovincialis there is a large sex-ratio bias in favor of
      either males or females. The degree of bias is a characteristic property of the
      female parent, as matings of the same female with different males produce the
      same sex ratio, but matings of the same male with different females produce
      different sex ratios. All three species possess the unusual feature of doubly
      uniparental inheritance of mitochondrial DNA (mtDNA); i.e., they contain two
      distinct types of mtDNA, one that is transmitted matrilinearly and one that is
      transmitted patrilinearly. This coupling of sex and mtDNA transmission raises the
      possibility that the mechanism of sex-ratio determination in mussels might be
      under the control of the mtDNA of the female parent. Here we present data from
      pedigreed crosses that confirm the previous observations that in mussel matings
      there is a strong sex-ratio bias and that the bias is under the control of the
      female parent. In addition, these data strongly suggest that this control is
      exercised by the mother's nuclear rather than mitochondrial genotype. Making use
      of these findings we develop a model of mother-dependent sex determination and
      use data from crosses involving wild females to test the model's predictions at
      the population level.

PMID- 12196403
TI  - Historical intensity of natural selection for resistance to tuberculosis.
AB  - Infections have long been thought to exert natural selection on humans.
      Infectious disease resistance is frequently invoked as a mechanism shaping human
      genetic diversity, but such hypotheses have rarely been quantitatively evaluated
      with direct measures of disease-related mortality. Enhancement of genetically
      determined resistance to tuberculosis by natural selection has been proposed as a
      factor explaining the decline of tuberculosis in Europe and North America in the
      period 1830-1950 (before the advent of antimicrobial chemotherapy) and the
      apparently reduced susceptibility of Europeans and their descendants to
      tuberculosis infection and/or disease. We used Swedish vital statistics from 1891
      to 1900 to estimate that individuals who escaped mortality from pulmonary
      tuberculosis (PTB) during the European tuberculosis epidemic would have enjoyed a
      fitness advantage of 7-15% per generation compared to individuals who were
      susceptible to PTB mortality; individuals with 50% protection would have had a
      selection coefficient of 4-7%/generation. Selection during the peak of the
      European TB epidemic could have substantially reduced the frequency of already
      rare alleles conferring increased susceptibility to PTB mortality, but only if
      the phenotypic effects of these alleles were very large. However, if resistant
      alleles were rare at the beginning of this period, 300 years would not have been
      long enough for such selection to increase their frequency to epidemiologically
      significant levels. Reductions in the frequency of rare susceptibility alleles
      could have played at most a small part in the decline of the epidemic in the
      century preceding 1950. Natural selection by PTB deaths during the European TB
      epidemic alone cannot account for the presently low level of TB disease observed
      among Europeans and their descendants just prior to the appearance of antibiotic
      treatment.

PMID- 12196405
TI  - Exploring alternative models for sex-linked quantitative trait loci in outbred
      populations: application to an iberian x landrace pig intercross.
AB  - We present a very flexible method that allows us to analyze X-linked quantitative
      trait loci (QTL) in crosses between outbred lines. The dosage compensation
      phenomenon is modeled explicitly in an identity-by-descent approach. A variety of
      models can be fitted, ranging from considering alternative fixed alleles within
      the founder breeds to a model where the only genetic variation is within breeds,
      as well as mixed models. Different genetic variances within each founder breed
      can be estimated. We illustrate the method with data from an F(2) cross between
      Iberian x Landrace pigs for intramuscular fat content and meat color component
      a*. The Iberian allele exhibited a strong overdominant effect for intramuscular
      fat in females. There was also limited evidence of one or more regions affecting
      color component a*. The analysis suggested that the QTL alleles were fixed in the
      Iberian founders, whereas there was some evidence of segregation in Landrace for
      the QTL affecting a* color component.

PMID- 12196404
TI  - Sequence variation and haplotype structure at the human HFE locus.
AB  - The HFE locus encodes an HLA class-I-type protein important in iron regulation
      and segregates replacement mutations that give rise to the most common form of
      genetic hemochromatosis. The high frequency of one disease-associated mutation,
      C282Y, and the nature of this disease have led some to suggest a selective
      advantage for this mutation. To investigate the context in which this mutation
      arose and gain a better understanding of HFE genetic variation, we surveyed
      nucleotide variability in 11.2 kb encompassing the HFE locus and experimentally
      determined haplotypes. We fully resequenced 60 chromosomes of African, Asian, or
      European ancestry as well as one chimpanzee, revealing 41 variable sites and a
      nucleotide diversity of 0.08%. This indicates that linkage to the HLA region has
      not substantially increased the level of HFE variation. Although several
      haplotypes are shared between populations, one haplotype predominates in Asia but
      is nearly absent elsewhere, causing higher than average genetic differentiation
      among the three major populations. Our samples show evidence of intragenic
      recombination, so the scarcity of recombination events within the C282Y allele
      class is consistent with selection increasing the frequency of a young allele.
      Otherwise, the pattern of variability in this region does not clearly indicate
      the action of positive selection at this or linked loci.

PMID- 12196406
TI  - Ethylnitrosourea-induced base pair substitution affects splicing of the mouse
      gammaE-crystallin encoding gene leading to the expression of a hybrid protein and
      to a cataract.
AB  - A novel ENU-induced mutation in the mouse leading to a nuclear and cortical
      opacity of the eye lens (ENU418) was mapped to proximal chromosome 1 by a genome
      wide mapping approach. It suggests that the cluster of gamma-crystallin encoding
      genes (Cryg) and the betaA2-crystallin encoding gene Cryba2 are excellent
      candidate genes. An A --> G exchange in the middle of intron 1 of the Cryge gene
      was found as the only alteration cosegregating with the cataractous phenotype.
      The mutation was confirmed by the presence of a novel restriction site for ApaI
      in the corresponding genomic DNA fragment. The mutation represses splicing of
      intron 1; the additional 92 bp in the corresponding cDNA leads to a frameshift
      and the expression of a novel hybrid protein containing 3 amino acids of the
      gammaE-crystallin at the N terminus, but 153 novel amino acids. The Cryge(ENU418)
      protein has a calculated molecular mass of approximately 15.6 kD and an alkaline
      isoelectric point (pH 10.1) and is predicted to have two hydrophobic domains.
      Western blot analysis using a polyclonal antibody against the hydrophilic C
      terminal part of the Cryge(ENU418)-specific protein demonstrated its stable
      expression in the cataractous lenses; it was not found in the wild types.
      Histological analysis of the cataractous lenses indicated that the expression of
      the new protein disrupts the cellular structure of the eye lens.

PMID- 12196407
TI  - The matrix coalescent and an application to human single-nucleotide
      polymorphisms.
AB  - The "matrix coalescent" is a reformulation of the familiar coalescent process of
      population genetics. It ignores the topology of the gene tree and treats the
      coalescent as a Markov process describing the decay in the number of ancestors of
      a sample of genes as one proceeds backward in time. The matrix formulation of
      this process is convenient when the population changes in size, because such
      changes affect only the eigenvalues of the transition matrix, not the
      eigenvectors. The model is used here to calculate the expectation of the site
      frequency spectrum under various assumptions about population history. To
      illustrate how this method can be used with data, we then use it in conjunction
      with a set of SNPs to test hypotheses about the history of human population size.

PMID- 12196408
TI  - X chromosome effect on maternal recombination and meiotic drive in the mouse.
AB  - We observed that maternal meiotic drive favoring the inheritance of DDK alleles
      at the Om locus on mouse chromosome 11 was correlated with the X chromosome
      inactivation phenotype of (C57BL/6-Pgk1(a) x DDK)F(1) mothers. The basis for this
      unexpected observation appears to lie in the well-documented effect of
      recombination on meiotic drive that results from nonrandom segregation of
      chromosomes. Our analysis of genome-wide levels of meiotic recombination in
      females that vary in their X-inactivation phenotype indicates that an allelic
      difference at an X-linked locus is responsible for modulating levels of
      recombination in oocytes.

PMID- 12196409
TI  - Chromosomal map of the model legume Lotus japonicus.
AB  - Lotus japonicus is a model plant for the legume family. To facilitate map-based
      cloning approaches and genome analysis, we performed an extensive
      characterization of the chromosome complement of the species. A detailed
      karyotype of L. japonicus Gifu was built and plasmid and BAC clones,
      corresponding to genetically mapped markers (see the accompanying article by
      Sandal et al. 2002, this issue), were used for FISH to correlate genetic and
      chromosomal maps. Hybridization of DNA clones from 32 different genomic regions
      enabled the assignment of linkage groups to chromosomes, the comparison between
      genetic and physical distances throughout the genome, and the partial
      characterization of different repetitive sequences, including telomeric and
      centromeric repeats. Additional analysis of L. filicaulis and its F(1) hybrid
      with L. japonicus demonstrated the occurrence of inversions between these closely
      related species, suggesting that these chromosome rearrangements are early events
      in speciation of this group.

PMID- 12196410
TI  - A genetic linkage map of the model legume Lotus japonicus and strategies for fast
      mapping of new loci.
AB  - A genetic map for the model legume Lotus japonicus has been developed. The F(2)
      mapping population was established from an interspecific cross between L.
      japonicus and L. filicaulis. A high level of DNA polymorphism between these
      parents was the source of markers for linkage analysis and the map is based on a
      framework of amplified fragment length polymorphism (AFLP) markers. Additional
      markers were generated by restriction fragment length polymorphism (RFLP) and
      sequence-specific PCR. A total of 524 AFLP markers, 3 RAPD markers, 39 gene
      specific markers, 33 microsatellite markers, and six recessive symbiotic mutant
      loci were mapped. This genetic map consists of six linkage groups corresponding
      to the six chromosomes in L. japonicus. Fluorescent in situ hybridization (FISH)
      with selected markers aligned the linkage groups to chromosomes as described in
      the accompanying article by Pedrosa et al. 2002(this issue). The length of the
      linkage map is 367 cM and the average marker distance is 0.6 cM. Distorted
      segregation of markers was found in certain sections of the map and linkage group
      I could be assembled only by combining colormapping and cytogenetics (FISH). A
      fast method to position genetic loci employing three AFLP primer combinations
      yielding 89 markers was developed and evaluated by mapping three symbiotic loci,
      Ljsym1, Ljsym5, and Ljhar1-3.

PMID- 12196411
TI  - Genetic architecture of plastic methyl jasmonate responses in Arabidopsis
      thaliana.
AB  - The ability of a single genotype to generate different phenotypes in disparate
      environments is termed phenotypic plasticity, which reflects the interaction of
      genotype and environment on developmental processes. However, there is
      controversy over the definition of plasticity genes. The gene regulation model
      states that plasticity loci influence trait changes between environments without
      altering the means within a given environment. Alternatively, the allelic
      sensitivity model argues that plasticity evolves due to selection of phenotypic
      values expressed within particular environments; hence plasticity must be
      controlled by loci expressed within these environments. To identify genetic loci
      controlling phenotypic plasticity and address this controversy, we analyzed the
      plasticity of glucosinolate accumulation under methyl jasmonate (MeJa) treatment
      in Arabidopsis thaliana. We found genetic variation influencing multiple MeJa
      signal transduction pathways. Analysis of MeJa responses in the Landsberg erecta
      x Columbia recombinant inbred lines identified a number of quantitative trait
      loci (QTL) that regulate plastic MeJa responses. All significant plasticity QTL
      also impacted the mean trait value in at least one of the two "control" or "MeJa"
      environments, supporting the allelic sensitivity model. Additionally, we present
      an analysis of MeJa and salicylic acid cross-talk in glucosinolate regulation and
      describe the implications for glucosinolate physiology and functional
      understanding of Arabidopsis MeJa signal transduction.

PMID- 12196412
TI  - A comparative genetic linkage map of eggplant (Solanum melongena) and its
      implications for genome evolution in the solanaceae.
AB  - A molecular genetic linkage map based on tomato cDNA, genomic DNA, and EST
      markers was constructed for eggplant, Solanum melongena. The map consists of 12
      linkage groups, spans 1480 cM, and contains 233 markers. Comparison of the
      eggplant and tomato maps revealed conservation of large tracts of colinear
      markers, a common feature of genome evolution in the Solanaceae and other plant
      families. Overall, eggplant and tomato were differentiated by 28 rearrangements,
      which could be explained by 23 paracentric inversions and five translocations
      during evolution from the species' last common ancestor. No pericentric
      inversions were detected. Thus, it appears that paracentric inversion has been
      the primary mechanism for chromosome evolution in the Solanaceae. Comparison of
      relative distributions of the types of rearrangements that distinguish pairs of
      solanaceous species also indicates that the frequency of different chromosomal
      structural changes was not constant over evolutionary time. On the basis of the
      number of chromosomal disruptions and an approximate divergence time for Solanum,
      approximately 0.19 rearrangements per chromosome per million years occurred
      during the evolution of eggplant and tomato from their last ancestor. This result
      suggests that genomes in Solanaceae, or at least in Solanum, are evolving at a
      moderate pace compared to other plant species.

PMID- 12196413
TI  - Conservation of gene function in the solanaceae as revealed by comparative
      mapping of domestication traits in eggplant.
AB  - Quantitative trait loci (QTL) for domestication-related traits were identified in
      an interspecific F(2) population of eggplant (Solanum linnaeanum x S. melongena).
      Although 62 quantitative trait loci (QTL) were identified in two locations, most
      of the dramatic phenotypic differences in fruit weight, shape, color, and plant
      prickliness that distinguish cultivated eggplant from its wild relative could be
      attributed to six loci with major effects. Comparison of the genomic locations of
      the eggplant fruit weight, fruit shape, and color QTL with the positions of
      similar loci in tomato, potato, and pepper revealed that 40% of the different
      loci have putative orthologous counterparts in at least one of these other crop
      species. Overall, the results suggest that domestication of the Solanaceae has
      been driven by mutations in a very limited number of target loci with major
      phenotypic effects, that selection pressures were exerted on the same loci
      despite the crops' independent domestications on different continents, and that
      the morphological diversity of these four crops can be explained by divergent
      mutations at these loci.

PMID- 12196414
TI  - General models of multilocus evolution.
AB  - In 1991, Barton and Turelli developed recursions to describe the evolution of
      multilocus systems under arbitrary forms of selection. This article generalizes
      their approach to allow for arbitrary modes of inheritance, including diploidy,
      polyploidy, sex linkage, cytoplasmic inheritance, and genomic imprinting. The
      framework is also extended to allow for other deterministic evolutionary forces,
      including migration and mutation. Exact recursions that fully describe the state
      of the population are presented; these are implemented in a computer algebra
      package (available on the Web at http://helios.bto.ed.ac.uk/evolgen). Despite the
      generality of our framework, it can describe evolutionary dynamics exactly by
      just two equations. These recursions can be further simplified using a "quasi
      linkage equilibrium" (QLE) approximation. We illustrate the methods by finding
      the effect of natural selection, sexual selection, mutation, and migration on the
      genetic composition of a population.

PMID- 12196415
TI  - Functional mapping of quantitative trait loci underlying the character process: a
      theoretical framework.
AB  - Unlike a character measured at a finite set of landmark points, function-valued
      traits are those that change as a function of some independent and continuous
      variable. These traits, also called infinite-dimensional characters, can be
      described as the character process and include a number of biologically,
      economically, or biomedically important features, such as growth trajectories,
      allometric scalings, and norms of reaction. Here we present a new statistical
      infrastructure for mapping quantitative trait loci (QTL) underlying the character
      process. This strategy, termed functional mapping, integrates mathematical
      relationships of different traits or variables within the genetic mapping
      framework. Logistic mapping proposed in this article can be viewed as an example
      of functional mapping. Logistic mapping is based on a universal biological law
      that for each and every living organism growth over time follows an exponential
      growth curve (e.g., logistic or S-shaped). A maximum-likelihood approach based on
      a logistic-mixture model, implemented with the EM algorithm, is developed to
      provide the estimates of QTL positions, QTL effects, and other model parameters
      responsible for growth trajectories. Logistic mapping displays a tremendous
      potential to increase the power of QTL detection, the precision of parameter
      estimation, and the resolution of QTL localization due to the small number of
      parameters to be estimated, the pleiotropic effect of a QTL on growth, and/or
      residual correlations of growth at different ages. More importantly, logistic
      mapping allows for testing numerous biologically important hypotheses concerning
      the genetic basis of quantitative variation, thus gaining an insight into the
      critical role of development in shaping plant and animal evolution and
      domestication. The power of logistic mapping is demonstrated by an example of a
      forest tree, in which one QTL affecting stem growth processes is detected on a
      linkage group using our method, whereas it cannot be detected using current
      methods. The advantages of functional mapping are also discussed.

PMID- 12196416
TI  - Antioxidant gene expression in active and sedentary house mice (Mus domesticus)
      selected for high voluntary wheel-running behavior.
AB  - We present liver mRNA levels of the two antioxidant enzymes catalase (CAT) and Mn
      superoxide dismutase (SOD2) in four treatment groups of house mice assayed by
      RNase protection at 20 months of age. These groups were mice from four replicate
      selection and four replicate control lines from the sixteenth generation of
      selective breeding for high voluntary wheel running, housed with or without
      running wheels from age 3 weeks through 20 months. Exercising control females had
      induced CAT expression; SOD2 exhibited a similar pattern in females from two of
      the four control lines. Exercising male mice had induced CAT expression, but not
      SOD2 expression, irrespective of genetic background. We discuss these results
      with respect to both evolutionary (genetic) and training (exercise-induced)
      adaptations and explore predictions of these results in relation to the oxidative
      damage theory of senescence.

PMID- 12196417
TI  - Spurious reporting of nocturnal hypoglycemia by CGMS in patients with tightly
      controlled type 1 diabetes.
AB  - OBJECTIVE: The Medtronic MiniMed Continuous Glucose Monitoring System (CGMS) is
      designed to continuously monitor interstitial fluid glucose levels within a range
      of 40-400 mg/dl. It is considered an important tool for overnight glucose
      monitoring. The goal of this study was to determine the accuracy of this system
      in individuals with tightly controlled diabetes. RESEARCH DESIGN AND METHODS:
      Seven adolescents and young adults with HbA(1c) levels 6.6 +/- 0.6% (range 5.7
      7.1) were admitted to the Clinical Research Center. Simultaneous glucose
      measurements obtained by glucose analyzer, Accu-Check Advantage meter, and CGMS
      were compared. The analyzer levels were considered the standard. RESULTS: The
      CGMS results were lower than analyzer readings in 74% of simultaneous pairs of
      tests performed during the 24-h period; the average correlation was 0.76. There
      was a trend for the poorest correlation to occur in patients with the narrowest
      range in daily glucose levels. When the lowest CGMS reading of the night was
      compared with the simultaneous analyzer reading, the CGMS level was lower in all
      cases by an average of 38 +/- 15%. In six of seven patients, the discrepancy was
      believed to be clinically significant; in at least four patients, overnight
      glucose levels reported by CGMS were falsely low, in a range that might have
      resulted in inappropriate reduction of overnight insulin dose. CONCLUSIONS: CGMS
      reports of asymptomatic nighttime hypoglycemia may be spurious and should be
      interpreted with caution in patients with tightly controlled diabetes.

PMID- 12196418
TI  - Improvement of BMI, body composition, and body fat distribution with lifestyle
      modification in Japanese Americans with impaired glucose tolerance.
AB  - OBJECTIVE: To determine whether diet and endurance exercise improved adiposity
      related measurements in Japanese Americans with impaired glucose tolerance (IGT).
      RESEARCH DESIGN AND METHODS: This study compared the effects of an American Heart
      Association (AHA) step 2 diet (<30% of total calories as fat, <7% saturated fat,
      55% carbohydrate, and < 200 mg cholesterol daily) plus endurance exercise for 1 h
      three times a week (treatment group) with an AHA step 1 diet (30% of total
      calories as fat, 10% saturated fat, 50% carbohydrate, and <300 mg cholesterol)
      plus stretching exercise three times a week (control group) on BMI, body
      composition (% fat), and body fat distribution at 6 and 24 months of follow-up in
      64 Japanese American men and women with IGT, 58 of whom completed the study.
      RESULTS: At 6 months, the treatment group showed significantly greater reduction
      in percent, body fat (-1.4 +/- 0.4 vs. -0.3 +/- 0.3%); BMI (-1.1 +/- 0.2 vs. -0.4
      +/- 0.1 kg/m(2)); subcutaneous fat by computed tomography at the abdomen (-29.3
      +/- 4.2 vs. -5.7 +/- 5.9 cm(2)), thigh (-13.2 +/- 3.6 vs. -3.6 +/- 3.0 cm(2)),
      and thorax (-19.6 +/- 3.6 vs. -8.9 +/- 2.6 cm(2)); and skinfold thickness at the
      bicep (-2.0 +/- 0.6 vs. 1.1 +/- 0.6 mm) and tricep (-3.7 +/- 0.8 vs. -0.9 +/- 0.6
      mm), which continued despite moving to home-based exercise for the last 18
      months. CONCLUSIONS: Diet and endurance exercise improved BMI, body composition,
      and body fat distribution and, thus, may delay or prevent type 2 diabetes in
      Japanese Americans with IGT.

PMID- 12196419
TI  - Diabetes contributes to cholesterol metabolism regardless of obesity.
AB  - OBJECTIVE: To investigate cholesterol metabolism in obesity with and without
      diabetes. RESEARCH DESIGN AND METHODS: We performed cross-sectional metabolic
      studies in obese individuals with and without type 2 diabetes. The study
      population consisted of 16 obese (BMI >30 kg/m(2)) diabetic subjects with a mean
      age of 52 +/- 2 years (SE) and 16 nondiabetic control subjects of similar age and
      weight. Cholesterol absorption efficiency was measured with peroral dual isotopes
      and cholesterol synthesis with sterol balance. RESULTS: Serum total cholesterol
      did not differ between the groups, but LDL and HDL cholesterol were significantly
      lower and VLDL cholesterol and serum total and VLDL triglycerides were higher in
      the diabetic group than in the control group. Cholesterol absorption efficiency
      was 29 +/- 1% in diabetic subjects vs. 42 +/- 2% in the control subjects (P <
      0.01). Cholesterol synthesis was higher (17 +/- 1 vs. 14 +/- 1 mg. kg(-1). day(
      1); P < 0.05) and neutral sterol and bile acid excretion and cholesterol turnover
      tended to be higher in the diabetic group than in the control group. Blood
      glucose was positively related to cholesterol synthesis in the diabetic group (r
      = +0.663, P < 0.01) and in the control group (r = +0.590, P < 0.05), suggesting
      that the higher blood glucose level, the higher the cholesterol synthesis. In
      addition, blood glucose was significantly positively related to fecal neutral
      sterol excretion in both groups. CONCLUSIONS: Cholesterol absorption efficiency
      was lower and cholesterol synthesis was higher in obese subjects with diabetes
      than in those without diabetes, suggesting that diabetes modulates cholesterol
      metabolism more than obesity alone.

PMID- 12196420
TI  - Treatment with dietary trans10cis12 conjugated linoleic acid causes isomer
      specific insulin resistance in obese men with the metabolic syndrome.
AB  - OBJECTIVE: Conjugated linoleic acid (CLA) is a group of dietary fatty acids with
      antiobesity and antidiabetic effects in some animals. The trans10cis12 (t10c12)
      CLA isomer seems to cause these effects, including improved insulin sensitivity.
      Whether such isomer-specific effects occur in humans is unknown. The aim of this
      study was to investigate whether t10c12 CLA or a commercial CLA mixture could
      improve insulin sensitivity, lipid metabolism, or body composition in obese men
      with signs of the metabolic syndrome. RESEARCH DESIGN AND METHODS: In a
      randomized, double-blind controlled trial, abdominally obese men (n = 60) were
      treated with 3.4 g/day CLA (isomer mixture), purified t10c12 CLA, or placebo.
      Euglycemic-hyperinsulinemic clamp, serum hormones, lipids, and anthropometry were
      assessed before and after 12 weeks of treatment. RESULTS: Baseline metabolic
      status was similar between groups. Unexpectedly, t10c12 CLA increased insulin
      resistance (19%; P < 0.01) and glycemia (4%; P < 0.001) and reduced HDL
      cholesterol (-4%; P < 0.01) compared with placebo, whereas body fat, sagittal
      abdominal diameter, and weight decreased versus baseline, but the difference was
      not significantly different from placebo. The CLA mixture did not change glucose
      metabolism, body composition, or weight compared with placebo but lowered HDL
      cholesterol (-2%; P < 0.05). CONCLUSIONS: These results reveal important isomer
      specific metabolic actions of CLA in abdominally obese humans. A CLA-induced
      insulin resistance has previously been described only in lipodystrophic mice.
      Considering the use of CLA-supplements among obese individuals, it is important
      to clarify the clinical consequences of these results, but they also provide
      physiological insights into the role of specific dietary fatty acids as
      modulators of insulin resistance in humans.

PMID- 12196421
TI  - Effect of wheat bran on glycemic control and risk factors for cardiovascular
      disease in type 2 diabetes.
AB  - OBJECTIVE: Cohort studies indicate that cereal fiber reduces the risk of diabetes
      and coronary heart disease (CHD). Therefore, we assessed the effect of wheat bran
      on glycemic control and CHD risk factors in type 2 diabetes. RESEARCH DESIGN AND
      METHODS: A total of 23 subjects with type 2 diabetes (16 men and 7 postmenopausal
      women) completed two 3-month phases of a randomized crossover study. In the test
      phase, bread and breakfast cereals were provided as products high in cereal fiber
      (19 g/day additional cereal fiber). In the control phase, supplements were low in
      fiber (4 g/day additional cereal fiber). RESULTS: Between the test and control
      treatments, no differences were seen in body weight, fasting blood glucose,
      HbA(1c), serum lipids, apolipoproteins, blood pressure, serum uric acid, clotting
      factors, homocysteine, C-reactive protein, magnesium, calcium, iron, or ferritin.
      LDL oxidation in the test phase was higher than that seen in the control phase
      (12.1 +/- 5.4%, P < 0.034). Of the subjects originally recruited, more dropped
      out of the study for health and food preference reasons from the control phase
      (16 subjects) than the test phase (11 subjects). CONCLUSIONS: High-fiber cereal
      foods did not improve conventional markers of glycemic control or risk factors
      for CHD in type 2 diabetes over 3 months. Possibly longer studies are required to
      demonstrate the benefits of cereal fiber. Alternatively, cereal fiber in the diet
      may be a marker for another component of whole grains that imparts health
      advantages or a healthy lifestyle.

PMID- 12196422
TI  - Combination therapy with nateglinide and a thiazolidinedione improves glycemic
      control in type 2 diabetes.
AB  - OBJECTIVE: To compare the effects of monotherapy using nateglinide and the
      thiazolidinedione troglitazone with initial combination of the two agents on
      glycated hemoglobin (HbA(1c)) in patients with type 2 diabetes inadequately
      controlled by diet alone. RESEARCH DESIGN AND METHODS: This study consisted of a
      28-week, double-blind, randomized, multicenter study that included a 4-week,
      single-blind, placebo, run-in period and a 24-week (shortened to 16 weeks),
      double-blind, active treatment period. RESULTS: At the 16-week end point,
      nateglinide 120 mg, troglitazone 600 mg, and the combination of the agents
      achieved statistically significant decreases in HbA(1c) in comparison with
      placebo and a baseline HbA(1c) of 8.1-8.4% (P < 0.001). The reductions in HbA(1c)
      were similar in the nateglinide (0.6%) and troglitazone (0.8%) monotherapy
      groups. The reduction in HbA(1c) (1.7%) was greatest in the combination group;
      79% of patients in the combination group achieved HbA(1c) levels of <7%. The
      combination group had a higher number of adverse events, primarily due to an
      increased incidence of mild hypoglycemia in this treatment group. CONCLUSIONS:
      Nateglinide and troglitazone are equally effective in decreasing HbA(1c) levels.
      However, these reductions from baseline HbA(1c) values of >8% are not adequate to
      achieve HbA(1c) levels of <7%. In contrast, the combination of nateglinide and of
      a thiazolidinedione shows an additive effect that is highly effective in reducing
      HbA(1c) levels to the target of <7% in 66% of patients, from a baseline HbA(1c)
      that is just above 8%.

PMID- 12196423
TI  - Acidic drinking water and risk of childhood-onset type 1 diabetes.
AB  - OBJECTIVE: To estimate the associations of acidity and concentration of selected
      minerals in household tap water with the risk of type 1 diabetes. RESEARCH DESIGN
      AND METHODS: We designed a population-based case-control study with 64 cases of
      type 1 diabetes and 250 randomly selected control subjects. Acidity, color, and
      mineral content were measured in tap water from each participant's household.
      RESULTS: Tap water pH 6.2-6.9 was associated with a fourfold higher risk of type
      1 diabetes compared with pH > or =7.7 (OR 3.73, 95% CI 1.52-9.15). This result
      was similar after exclusion of individuals with the highly protective HLA
      DQB1*0602 allele, but adjustment for maternal education, urban/rural residence,
      sex, and age tended to strengthen the estimated association. Higher tap water
      concentration of zinc was associated with lower risk of type 1 diabetes after
      adjustment for pH and other possible confounders, but the overall association was
      strictly not significant. CONCLUSIONS: These results suggest the possibility that
      quality of drinking water influences the risk of type 1 diabetes. The possible
      mechanisms by which water acidity or mineral content may be involved in the
      etiology of type 1 diabetes remain unknown, but the mechanisms are most likely
      indirect and may involve an influence on survival of microorganisms in the water.

PMID- 12196424
TI  - Fetal overnutrition in polynesian pregnancies and in gestational diabetes may
      lead to dysregulation of the adipoinsular axis in offspring.
AB  - OBJECTIVE: To compare umbilical cord leptin concentrations in different ethnic
      groups and between pregnancies with and without gestational diabetes mellitus
      (GDM) in Auckland, New Zealand. RESEARCH DESIGN AND METHODS: A cross-sectional
      study of 116 European, Polynesian, and South Asian women and their infants with
      and without GDM. Maternal metabolic measures were recorded at 36 weeks'
      gestation, umbilical cord samples were collected at birth, and neonatal
      anthropometric measures were recorded 24 h after delivery. RESULTS: Compared with
      Europeans and South Asians, samples of Polynesian umbilical cords had higher
      leptin concentrations (8.7 and 9.5 vs. 14.9 ng/ml, respectively; P = 0.026).
      Umbilical cord samples from pregnancies complicated by GDM had higher leptin
      concentrations than those from normal pregnancies (22.3 vs. 13.8 ng/ml,
      respectively; P = 0.022). Maternal leptin concentrations at 36 weeks were similar
      across ethnic groups and with and without GDM. Cord leptin correlated with birth
      weight, measures of fetal size, and cord insulin in normal pregnancies and those
      complicated by GDM. In multivariate analyses, cord leptin was related to birth
      weight (P < 0.001), gestation at delivery (P = 0.038), and ethnic group (P =
      0.017) in normal pregnancies and to birth weight (P < 0.001), gestation at
      delivery (P < 0.001), and sex (P = 0.003) but not maternal diabetes status (P =
      0.909) in pregnancies complicated by GDM. CONCLUSIONS: Offspring of Polynesian
      women are relatively hyperleptinemic, independent of birth size. Offspring of
      women with GDM are also relatively hyperleptinemic at birth, but this was
      associated with their increased birth weight. We speculate that this GDM
      associated relative hyperleptinemia may be due to fuel-mediated teratogenesis
      affecting the adipoinsular axis, which in turn could also lead to leptin
      resistance and obesity in adult life. The reason for the ethnic difference in
      hyperleptinemia is unclear.

PMID- 12196425
TI  - Pupil signs of sympathetic autonomic neuropathy in patients with type 1 diabetes.
AB  - OBJECTIVE: Pupillary autonomic neuropathy is considered an early sign of the
      development of systemic autonomic neuropathy. Sympathetic denervation is related
      to the duration of diabetes and the development of systemic autonomic
      dysfunction. We investigated pupil responsiveness to directly and indirectly
      acting sympathomimetics in type 1 diabetic patients with and without long-term
      complications, defined as cardiac autonomic neuropathy (CAN), peripheral
      sensomotor neuropathy, retinopathy, and nephropathy, and in healthy subjects.
      RESEARCH DESIGN AND METHODS: A total of 47 randomly chosen type 1 diabetic
      patients and 20 healthy subjects were selected for this study. Patients were
      divided into groups determined by whether they had long-term diabetic
      complications. Pharmacological tests were performed with cocaine 4%, epinephrine
      1%, and pholedrine 5% eye drops. Horizontal pupil diameter (HPD) was measured at
      the beginning of the pharmacological tests and at defined time points after
      instillation of the eye drops. RESULTS: Statistical analysis showed a
      significantly smaller HPD in the patients before instillating eye drops (P =
      0.011). In particular, the HPD was significantly smaller in the patient group
      without CAN when compared with healthy subjects (P = 0.004). Maximal cocaine
      reaction was diminished in the complication group (P < 0.001). Epinephrine test,
      visual acuity, ocular pressure, and HbA(1c) did not differ in patients with or
      without long-term complications. The noncomplication group showed no significant
      differences in pupillary responses as compared with healthy subjects. The
      complication group showed a smaller HPD (P = 0.022), reduced pupillary responses
      in the cocaine (P = 0.037) and pholedrine tests (P < 0.001), and anisocor pupil
      sizes after instillation of the eye drops (P = 0.034). CONCLUSIONS: Our results
      clearly show that sympathetic denervation does exist in the pupil of diabetic
      patients and that it can be rapidly assessed using the cocaine test. These data
      and the results of the epinephrine test suggest a mixed pre- and postganglionic
      dysfunction of the sympathetic plexus. The significant smaller HPD in patients
      without CAN compared with that of healthy subjects could be a sign for early
      involvement of the pupil function before cardiac manifestation of systemic
      autonomic diabetic neuropathy.

PMID- 12196426
TI  - Population-based study of diabetes and risk characteristics in Turkey: results of
      the turkish diabetes epidemiology study (TURDEP).
AB  - OBJECTIVES: To investigate for the first time the prevalence of diabetes and
      impaired glucose tolerance (IGT) nationwide in Turkey; to assess regional
      variations and relationships between glucose intolerance and lifestyle and
      physical risk factors. RESEARCH DESIGN AND METHODS: The Turkish Diabetes
      Epidemiology Study (TURDEP) is a cross-sectional, population-based survey that
      included 24,788 subjects (age > or =20 years, women 55%, response 85%). Glucose
      tolerance was classified according to World Health Organization recommendations
      on the basis of 2-h blood glucose values. RESULTS: Crude prevalence of diabetes
      was 7.2% (previously undiagnosed, 2.3%) and of IGT, 6.7% (age-standardized to
      world and European populations, 7.9 and 7.0%). Both were more frequent in women
      than men (P < 0.0001) and in those living in urban rather than rural communities
      (P < 0.001). Prevalence rates of hypertension and obesity were 29 and 22%,
      respectively. Both were more common among women than men (P < 0.0001). Prevalence
      of diabetes and IGT increased with rising BMI, waist-to-hip ratio (WHR), and
      waist girth (P < 0.0001). Multiple logistic regression analysis revealed that
      age, BMI, WHR, familial diabetes, and hypertension were independently associated
      with diabetes, age, BMI, WHR, familial diabetes, and hypertension with IGT
      (except for familial diabetes in women with IGT). Education was related to
      diabetes in men but was protective for diabetes and IGT in women. Socioeconomic
      status appeared to decrease the risk of IGT in men while it increased the risk in
      women. Smoking had a protective effect for IGT in both sexes. CONCLUSIONS:
      Diabetes and IGT are moderately common in Turkey by international standards.
      Associations with obesity and hypertension have been confirmed. Other lifestyle
      factors had a variable relationship with glucose tolerance.

PMID- 12196427
TI  - All-cause and cardiovascular mortality among diabetic participants in the San
      Antonio Heart Study: evidence against the "Hispanic Paradox".
AB  - OBJECTIVE: The observation that Hispanics have lower all-cause and cardiovascular
      mortality, despite increased diabetes and obesity, lower socioeconomic status
      (SES), and barriers to health care, has been termed the "Hispanic Paradox." We
      examined the relationship between ethnicity and all-cause and cardiovascular
      mortality in Mexican Americans (MAs) and non-Hispanic whites (NHWs) with
      diabetes. RESEARCH DESIGN AND METHODS: In the San Antonio Heart Study, a
      prospective cohort, we compared the mortality in 554 U.S.-born MAs, 95 Mexico
      born MAs, and 178 NHW participants with diabetes aged 25-72 years. Over an
      average of 10.4 years, 188 deaths occurred: 115 from cardiovascular disease (CVD)
      [death certificate ICD-9 codes 401-414 or 420-447 (excluding 427.5)]. Because of
      potential differences between migrants and nonmigrants, hazard ratios (HRs) were
      calculated comparing U.S.-born MAs and Mexico-born MAs with NHWs. RESULTS: The
      age- and sex-adjusted HR for all-cause mortality comparing U.S.-born MAs with
      NHWs was 1.66 (95% CI 1.15-2.40), while comparing Mexico-born MAs with NHWs was
      1.14 (95% CI 0.63-2.06). Cardiovascular mortality HRs were 1.66 (95% CI 1.04
      2.65) and 0.89 (95% CI 0.40-2.01), respectively. After adjusting for possible
      confounders, such as fasting glucose and diabetes duration, the hazard of all
      cause and cardiovascular mortality (although not statistically significant)
      appeared higher in U.S.-born MAs than in the other two groups. CONCLUSIONS: We
      found it important to differentiate MAs by birthplace. Among diabetic
      participants, contrary to the prediction of the "Hispanic Paradox," compared with
      NHWs, U.S.-born MAs were at greater risk of all-cause and cardiovascular
      mortality, while Mexico-born MAs appeared to be at similar risk.

PMID- 12196428
TI  - Depression and anxiety among partners of European-American and Latino patients
      with type 2 diabetes.
AB  - OBJECTIVE: To assess the levels of and the independent contributors to depressive
      affect and anxiety among partners of patients with type 2 diabetes. RESEARCH
      DESIGN AND METHODS: The partners of 75 Latino and 113 European-American patients
      with type 2 diabetes were assessed for level of depressive affect and anxiety and
      for three groups of potential stressors: demographics (age, gender, and
      education), patient disease status (time since diagnosis, HbA(1c), comorbidities,
      and BMI), and family stress (disease impact, spouse conflict, and family
      closeness). Dependent variables were partner depressive affect (Center for
      Epidemiological Studies-Depression scale) and anxiety (Symptom Checklist [SCL-90]
      anxiety). Predictors of partner depressive affect and anxiety and partner-patient
      concordance rates were computed. RESULTS: Levels of depressive affect and anxiety
      and rates of likely depression (21.4%) were as high for partners as they were for
      patients. No differences were found on depressive affect or anxiety by ethnicity,
      but female partners scored higher than male partners on both measures. Partner
      patient concordance rates were low. The family level variables accounted for the
      most variance in both depressive affect and anxiety, with demographics and
      disease status variables contributing modest or nonsignificant independent
      variance. CONCLUSIONS: Partners of patients with type 2 diabetes experience
      levels of psychological distress as high or even higher than patients, especially
      if the partner is female. Low levels of concordance suggest that partners can be
      distressed even if patients are not. Many life stresses contribute to
      psychological distress among partners, not just disease-related indicators. The
      findings suggest the utility of evaluating both partners and patients using a
      life-centered rather than a disease-focused perspective.

PMID- 12196429
TI  - Classification of type 1 diabetic females with bulimia nervosa into subgroups
      according to purging behavior.
AB  - OBJECTIVE: To classify type 1 diabetic females with bulimia nervosa (BN) by type
      of inappropriate compensatory behavior in order to prevent weight gain (ICB) and
      to investigate the group differences. RESEARCH DESIGN AND METHODS: Type 1
      diabetic females with BN, diagnosed by structured diagnostic interview based on
      DSM-IV (Diagnostic and Statistical Manual of Mental Disorders, 4th ed.) criteria,
      were classified by type of ICB as follows: 1) only severe insulin omission as an
      ICB (BN-I) (n = 22), 2) both severe insulin omission and self-induced vomiting
      and/or laxative abuse (BN-IP) (n = 22), or 3) no insulin omission but another ICB
      (BN-NI) (n = 11). The clinical characteristics of these three groups and a binge
      eating disorder (BED) group (n = 24) were compared. RESULTS: The BN-IP and BN-I
      groups had the highest HbA(1c) levels. The BN-IP group had the highest rates of
      diabetic neuropathy, retinopathy, and nephropathy. The BN-NI group had the second
      highest rates of neuropathy and retinopathy. The BN-IP group had the highest
      frequencies of diabetes- and ketoacidosis-related hospital admissions, and the BN
      I group had the second highest frequencies. The BN-NI group showed the highest
      scores on psychological tests related to depression, anxiety, eating disorder
      psychopathology, and perfectionism. The BN-NI group had the highest rate of
      history of visits to a psychiatrist, and the BN-IP group had the second highest
      history. CONCLUSIONS: Type 1 diabetic females with BN seem not to be homogenous
      and can be classified into three distinctive subgroups by type of ICB.
      Individuals with BN-IP had the most severe problems with both medical and
      psychological/behavioral aspects. Individuals with BN-NI manifested the highest
      psychological distress. The BN-I group had comparatively mild distress despite
      having the poorest metabolic control. Each BN group manifested more severe
      pathology than the BED group.

PMID- 12196430
TI  - A randomized trial of an intervention to improve self-care behaviors of African
      American women with type 2 diabetes: impact on physical activity.
AB  - OBJECTIVE: To determine whether a culturally appropriate clinic- and community
      based intervention for African-American women with type 2 diabetes will increase
      moderate-intensity physical activity (PA). RESEARCH DESIGN AND METHODS: In this
      randomized controlled trial conducted at seven practices in central North
      Carolina, 200 African-American women, > or =40 years of age with type 2 diabetes,
      were randomized to one of three treatment conditions: clinic and community (group
      A), clinic only (group B), or minimal intervention (group C). The clinic-based
      intervention (groups A and B) consisted of four monthly visits with a
      nutritionist who provided counseling to enhance PA and dietary intake that was
      tailored to baseline practices and attitudes; the community-based intervention
      (group A) consisted of three group sessions and 12 monthly phone calls from a
      peer counselor and was designed to provide social support and reinforce behavior
      change goals; and the minimal intervention (group C) consisted of educational
      pamphlets mailed to participants. The primary study outcome was the comparison of
      PA levels between groups assessed at 6 and 12 months by accelerometer, which was
      worn while awake for 7 days. RESULTS: Totals of 175 (88%) and 167 (84%)
      participants completed PA assessment at 6 and 12 months, respectively. For
      comparison of PA, the P value for overall group effect was 0.014. Comparing group
      A with C, the difference in the average adjusted mean for PA was 44.1 kcal/day
      (95% CI 13.1-75.1, P = 0.0055). Comparing group B with C, the difference in the
      average adjusted mean was 33.1 kcal/day (95% CI 3.3-62.8, P = 0.029). The
      intervention was acceptable to participants: 88% were very satisfied with clinic
      based counseling to enhance PA, and 86% indicated that the peer counselor's role
      in the program was important. CONCLUSIONS: The intervention was associated with a
      modest enhancement of PA and was acceptable to participants.

PMID- 12196431
TI  - Influence of health care providers on the development of diabetes complications:
      long-term follow-up from the Pittsburgh Epidemiology of Diabetes Complications
      Study.
AB  - OBJECTIVE: To quantify total diabetes care received (generalist or specialist)
      from diagnosis onward and its association with the incidence of diabetes
      complications in a representative cohort of patients with type 1 diabetes.
      RESEARCH DESIGN AND METHODS: A total of 429 subjects from the Pittsburgh
      Epidemiology of Diabetes Complications Study, a prospective follow-up study of
      childhood-onset type 1 diabetic subjects first seen between 1986 and 1988 (mean
      age 28 years, mean duration 19 years), followed biennially for up to 10 years
      were studied. Specialist care was defined as care received from a board-certified
      endocrinologist, diabetologist, or diabetes clinic and quantified as the percent
      of diabetes duration spent in specialist care. RESULTS: There was a significant
      trend for a higher incidence of neuropathy, overt nephropathy, and coronary
      artery disease with lower use of specialist care. Multivariate analyses
      controlling for diabetes duration, demographic characteristics, health care
      practices, and physiological risk factors demonstrated that higher past use of
      specialist care was found to be significantly protective against the development
      of overt nephropathy (risk ratio 0.43, 95% CI 0.21-0.88) and neuropathy (0.54,
      0.35-0.83) and weakly protective against coronary artery disease (0.65, 0.37
      1.1). CONCLUSIONS: A higher proportion of diabetes duration spent in specialist
      care may result in delayed development of certain diabetes complications
      independent of other risk factors. This study thus supports the concept that the
      benefits of specialist care should be available to all patients with type 1
      diabetes.

PMID- 12196432
TI  - Recent trends in hospitalization for diabetic ketoacidosis in ontario children.
AB  - OBJECTIVE: To investigate trends and geographic variation in diabetic
      ketoacidosis (DKA) hospitalization rates among children in Ontario from 1991 to
      1999. RESEARCH DESIGN AND METHODS: Canadian Institute for Health Information
      (CIHI) data were used to identify 15,872 diabetes-related hospital admissions in
      children younger than 19 years in Ontario from 1991 to 1999. Of these, 5,008
      admissions were because of DKA and 10,864 admissions were because of conditions
      other than DKA (non-DKA). Small area variation analysis was used to compare areas
      with high versus low DKA admission rates. RESULTS: There was a 19% relative
      decrease in the overall diabetes admission rate over the study period. Non-DKA
      admissions decreased by 29%, whereas DKA admissions remained stable. Total days
      of care decreased by 393 days per year for non-DKA admissions and by 99 days per
      year for DKA admissions. The average length of hospital stay decreased from 4.9
      to 3.5 days for non-DKA admissions and from 4.5 to 3.2 days for DKA admissions.
      The fatality rate was 0.19% for non-DKA admissions and 0.18% for DKA admissions.
      Variation across geographic areas remained stable for DKA over the study period
      (Kendall's correlation coefficient 0.64, P = 0.017) with an average 3.7-fold
      difference between the lowest and highest regions. CONCLUSIONS: Increased
      ambulatory care efforts for children with type 1 diabetes in Ontario have
      successfully reduced non-DKA admission rates. However, DKA admission rates have
      remained stable. Geographic variation for DKA admissions is low, but the observed
      3.7-fold difference is clinically important for a preventable complication with a
      significant potential for long-term morbidity and mortality. Prevention
      strategies are needed, particularly in areas identified with the highest rates.

PMID- 12196433
TI  - Intravenous glargine and regular insulin have similar effects on endogenous
      glucose output and peripheral activation/deactivation kinetic profiles.
AB  - OBJECTIVE: To compare the effects of intravenously administered long-acting
      insulin analog glargine and regular human insulin on activation and deactivation
      of endogenous glucose output (EGO) and peripheral glucose uptake. RESEARCH DESIGN
      AND METHODS: In this single-center, randomized, double-blind, crossover
      euglycemic glucose clamp study, 15 healthy male volunteers (aged 27 +/- 4 years,
      BMI 24.2 +/- 0.7 kg/m(2) [mean +/- SE]) received a primed continuous intravenous
      infusion of 40 mU/m(2) of insulin glargine or regular human insulin on 2
      different study days in a randomized order. Euglycemia was maintained at 90 mg/dl
      using a simultaneous variable intravenous infusion of 20% dextrose containing D
      [3-(3)H]glucose. EGO and peripheral glucose disposal kinetics were determined
      during a 4-h insulin infusion activation period and a 3-h deactivation period.
      RESULTS: The results demonstrated no significant difference in activation or
      deactivation kinetics with respect to EGO and peripheral glucose disposal between
      insulin glargine and regular human insulin when given intravenously. The mean +/-
      SE time required for 50% suppression of EGO after insulin infusion was 73 +/- 23
      min for regular insulin and 57 +/- 20 min for insulin glargine (NS). The mean
      maximum rate of glucose disposal was 10.10 +/- 0.77 and 9.90 +/- 0.85 mg. kg(-1).
      min(-1) for regular insulin and insulin glargine, respectively (NS). The mean
      time required for 50% suppression of incremental glucose disposal rate (GDR),
      defined as the time required for activation from the basal glucose disappearance
      rate (R(d)) to half-maximum insulin-stimulated R(d), was 32 +/- 5 and 42 +/- 10
      min for regular insulin and insulin glargine, respectively (NS). The time
      required for deactivation from maximum insulin-stimulated GDR to half-maximum GDR
      after cessation of insulin infusion was 63 +/- 5 and 57 +/- 4 min for regular
      insulin and insulin glargine, respectively (NS). CONCLUSIONS: Activation and
      deactivation kinetics of EGO and peripheral glucose uptake as well as absolute
      disposal rate are similar between regular human insulin and insulin glargine when
      administered intravenously. Thus, the various biological actions of these insulin
      preparations when given subcutaneously are completely due to their different
      absorption kinetics.

PMID- 12196434
TI  - Evaluation of conventional blood glucose monitoring as an indicator of integrated
      glucose values using a continuous subcutaneous sensor.
AB  - OBJECTIVE: To use a portable continuous glucose monitoring system (CGMS) to
      evaluate how well the customary intermittent self-monitoring of blood glucose
      (SMBG) correlates with integrated values during the surrounding time periods in
      ambulatory patients with type 1 diabetes. RESEARCH DESIGN AND METHODS: In the
      study, 18 young patients with type 1 diabetes were monitored with CGMS for up to
      72 h, during which they continued to perform the four standard SMBG tests
      (preprandial and bedtime). Correlations were examined between each of the four
      standard SMBG tests and the mean CGMS values from defined periods that preceded
      and followed. We also tested how well a low bedtime SMBG predicted nocturnal
      hypoglycemia. RESULTS: Strong correlations were found between 1) SMBG at
      breakfast and the mean CGMS value for the preceding 8 h (r = 0.7514), 2) SMBG at
      dinner and the CGMS from lunch to dinner (r = 0.7538), 3) SMBG at bedtime and the
      CGMS from dinner to bedtime (r = 0.8145), and 4) SMBG at bedtime and the CGMS
      from bedtime to breakfast (r = 0.6463). The remaining correlations were weak and
      not statistically significant. These correlations seem independent of insulin
      delivery method as virtually identical results were obtained when data from
      patients on conventional versus intensive regimes were separately analyzed. A
      bedtime SMBG <7 mmol/l did not predict nocturnal hypoglycemia (defined as at
      least one CGMS value <3). CONCLUSIONS: -The breakfast and dinnertime SMBG values
      are good indicators of integrated glucose values in the time period preceding
      them, while the bedtime test correlates well with the integrated values both
      preceding and following it. This information should aid in the meaningful use of
      SMBG to evaluate glycemic control and make insulin dose adjustments.

PMID- 12196435
TI  - Glimepiride improves both first and second phases of insulin secretion in type 2
      diabetes.
AB  - OBJECTIVE: The purpose of this study was to assess the effect of glimepiride on
      insulin sensitivity and secretion in subjects with type 2 diabetes. RESEARCH
      DESIGN AND METHODS: After a 2-week washout from prior sulfonylurea therapy, 11
      obese subjects with type 2 diabetes underwent euglycemic and hyperglycemic clamp
      studies before and during glimepiride therapy. RESULTS: Glimepiride resulted in a
      2.4-mmol/l decrease in fasting plasma glucose (P = 0.04) that was correlated with
      reductions in postabsorptive endogenous glucose production (EGP) (16.4 +/- 0.6
      vs. 13.5 +/- 0.5 micro mol. kg(-1). min(-1), P = 0.01) (r = 0.21, P = 0.01).
      Postabsorptive EGP on glimepiride was similar to that of control subjects (12.8
      +/- 0.9 micro mol. kg(-1). min(-1), NS). Fasting plasma insulin (66 +/- 18 vs. 84
      +/- 48 pmol/l, P = 0.05), and first-phase (19 +/- 8 vs. 32 +/- 11 pmol/l, P =
      0.04) and second-phase incremental insulin responses to glucose (48 +/- 23 vs. 72
      +/- 32 pmol/l, P = 0.02) improved with glimepiride therapy. Insulin sensitivity
      did not change with treatment (4.6 +/- 0.7 vs. 4.3 +/- 0.7 micro mol. kg(-1).
      min(-1). pmol(-1)) and remained below that of control subjects (8.1 +/- 1.8 micro
      mol. kg(-1). min(-1). pmol(-1), P = 0.04). CONCLUSIONS: The current study
      demonstrates that glimepiride improves both first and second phases of insulin
      secretion, but not insulin sensitivity, in individuals with type 2 diabetes.

PMID- 12196436
TI  - Low levels of leisure-time physical activity and cardiorespiratory fitness
      predict development of the metabolic syndrome.
AB  - OBJECTIVE: Little is known about the association of leisure-time physical
      activity (LTPA) and cardiorespiratory fitness with development of the metabolic
      syndrome, which predisposes diseases such as diabetes and atherosclerosis. We
      studied the associations of LTPA and cardiorespiratory fitness with development
      of the metabolic syndrome (World Health Organization [WHO] and the National
      Cholesterol Education Program [NCEP] definitions). RESEARCH DESIGN AND METHODS:
      LTPA over the previous 12 months, VO(2max) (ml. kg(-1). min(-1)), and
      cardiovascular and metabolic risk factors were assessed in a population-based
      cohort of 612 middle-aged men without the metabolic syndrome. RESULTS: At the 4
      year follow-up, 107 men had metabolic syndrome (WHO definition). Men engaging in
      >3 h/week of moderate or vigorous LTPA were half as likely as sedentary men to
      have the metabolic syndrome after adjustment for major confounders (age, BMI,
      smoking, alcohol, and socioeconomic status) or potentially mediating factors
      (insulin, glucose, lipids, and blood pressure), especially in high-risk men.
      Vigorous LTPA had an even stronger inverse association, particularly in unfit
      men. Men in the upper third of VO(2max) were 75% less likely than unfit men to
      develop the metabolic syndrome, even after adjustment for major confounders.
      Adjustment for possible mediating factors attenuated the association.
      Associations of LTPA and VO(2max) with development of the metabolic syndrome, as
      defined by the NCEP, were qualitatively similar. CONCLUSIONS: In particular, high
      risk men engaging in currently recommended levels of physical activity were less
      likely to develop the metabolic syndrome than sedentary men. Cardiorespiratory
      fitness was also strongly protective, although possibly not independent of
      mediating factors.

PMID- 12196437
TI  - Women with impaired glucose tolerance during pregnancy have significantly poor
      pregnancy outcomes.
AB  - OBJECTIVE: This article tests the hypothesis that women with impaired glucose
      tolerance (IGT) have the same pregnancy outcomes as those of their counterparts
      with normal glucose tolerance. RESEARCH DESIGN AND METHODS: From December 1998 to
      December 1999, 84 of 90 antenatal care base units (ACBUs) under the Tianjin
      Antenatal Care Network in China participated in the first screening program for
      gestational diabetes mellitus (GDM). A total of 9,471 pregnant women under the
      care of participating ACBUs were screened. Of the women screened, 154 were
      positive for IGT. Of the 154 women, 102 opted for conventional obstetric care.
      The comparison group was 302 women of normal glucose tolerance (NGT). The initial
      screening consisted of a 50-g 1-h glucose test, and was carried out at 26-30
      gestational weeks. Women with a serum glucose > or =7.8 mmol/l were followed up
      with a 75-g 2-h oral glucose tolerance test. The World Health Organization's
      diagnostic criteria for GDM were used. RESULTS: Women with IGT were at increased
      risk for premature rupture of membranes (P-ROM) (odds ratio [OR] 10.07; 95% CI
      2.90-34.93); preterm birth (6.42; 1.46-28.34); breech presentation (3.47; 1.11
      10.84); and high birth weight (90th percentile or 4,000 g) (2.42; 1.07-5.46);
      adjusting for maternal age, pregravid BMI, hospital levels, and other confounding
      factors. CONCLUSIONS: The presence of IGT in pregnancy is predictive of poor
      pregnancy outcomes.

PMID- 12196438
TI  - Prevalence of gestational diabetes mellitus detected by the national diabetes
      data group or the carpenter and coustan plasma glucose thresholds.
AB  - OBJECTIVE: In 2000, the American Diabetes Association proposed the adoption of
      the Carpenter and Coustan criteria for diagnosis of gestational diabetes mellitus
      (GDM). The Carpenter and Coustan cutoffs are lower than the previously
      recommended National Diabetes Data Group (NDDG) values and would result in higher
      prevalence of GDM. Our aim is to estimate the magnitude of change in prevalence
      of GDM using the Carpenter and Coustan thresholds as compared with the NDDG
      thresholds by age and ethnicity. RESEARCH DESIGN AND METHODS: Cross-sectional
      study of 28,330 women aged 14-49 years who gave birth in 1996 and were members of
      the Northern California Kaiser Permanente Medical Care Program. Age, ethnicity,
      screening, and diagnostic test results were assessed from computerized
      hospitalization and laboratory systems. RESULTS: A total of 26,481 (94%) women
      were screened using a 50-g, 1-h oral glucose tolerance test, and 4,190 women
      underwent a diagnostic 100-g, 3-h oral glucose tolerance test after an abnormal
      screening. Overall, the GDM prevalence among screened women was 3.2% (95% CI 3.0
      3.4) by NDDG and 4.8% (95% CI 4.5-5.1) by Carpenter and Coustan criteria, and
      based on either threshold, it increased with age (P < 0.001). The age-adjusted
      GDM prevalence by NDDG and Carpenter and Coustan criteria, respectively, was 5.0
      and 7.4% in Asians, 3.9 and 5.6% in Hispanics, 3.0 and 4.0% in African-Americans,
      and 2.4 and 3.8% in whites. Proportional increments were larger in women aged <25
      years (70%) and in whites (58%). CONCLUSIONS: -The prevalence of GDM increased,
      on average, by 50% with use of the Carpenter and Coustan thresholds. Relative
      increments were greater in low-risk age and ethnic groups. This information would
      be useful for clinical settings in predicting cost of GDM based on demographic
      characteristics of the population.

PMID- 12196439
TI  - Unique effect of visceral fat on insulin sensitivity in obese Hispanic children
      with a family history of type 2 diabetes.
AB  - OBJECTIVE: This study aimed to establish whether total fat or central fat was
      related to measures of insulin in obese Hispanic children with a family history
      of type 2 diabetes. RESEARCH DESIGN AND METHODS: Subjects were 32 children aged 8
      13 years. Visceral fat and subcutaneous abdominal fat were determined by magnetic
      resonance imaging at the umbilicus and total body fat was determined by dual
      energy X-ray absorptiometry. Insulin sensitivity (S(i)) and acute insulin
      response (AIR) were determined by frequently sampled intravenous tolerance test
      with minimal modeling. RESULTS: Mean fasting glucose and insulin, S(i), and AIR
      (+/- SD) were 5.3 +/- 0.3 mmol/l, 206 +/- 105 pmol/l, 11.8 +/- 5.7 [x 10(-4) min(
      1)/(pmol/l)], and 17,175 +/- 9,695 (pmol/l x 10 min), respectively. In
      multivariate regression analysis, total fat mass was independently and positively
      related to fasting insulin (P < 0.01) and negatively related to S(i) (P < 0.05)
      but was not related to AIR. Visceral fat was independently and positively related
      to fasting insulin (P < 0.05) and AIR (P < 0.01) and negatively related to S(i)
      (P < 0.001). CONCLUSIONS: -These findings support the hypothesis that specific
      accumulation of visceral fat in addition to overall adiposity in Hispanic
      children increases the risk of type 2 diabetes.

PMID- 12196440
TI  - Prognostic value of dobutamine-atropine stress myocardial perfusion imaging in
      patients with diabetes.
AB  - OBJECTIVE: Exercise tolerance in patients with diabetes is frequently impaired
      due to noncardiac disease such as claudication and polyneuropathy. This study
      assesses the prognostic value of dobutamine stress myocardial perfusion imaging
      in patients with diabetes. RESEARCH DESIGN AND METHODS: A total of 207
      consecutive diabetic patients who were unable to undergo exercise stress testing
      underwent dobutamine-atropine stress myocardial perfusion imaging. Follow-up was
      successful in 206 of 207 (99.5%) patients. A total of 12 patients underwent early
      (<60 days) revascularization and were excluded from the analysis. End points
      during follow-up were hard cardiac events, defined as cardiac death and nonfatal
      myocardial infarction. RESULTS: Abnormal myocardial perfusion was detected in 125
      (64%) patients. During 4.1 +/- 2.4 years of follow-up, 73 (38%) deaths occurred,
      36 (49%) of which were due to cardiac causes. Nonfatal myocardial infarction
      occurred in 7 (4%) patients, and 45 (23%) patients underwent late coronary
      revascularization. Cardiac death occurred in 2 of 69 (3%) patients with normal
      myocardial perfusion and in 34 of 125 (27%) patients with perfusion abnormalities
      (P < 0.0001). A multivariable Cox proportional hazard model demonstrated that, in
      addition to clinical and stress test data, an abnormal scan had an incremental
      prognostic value for prediction of cardiac death (hazard ratio 7.2, 95% CI 1.7
      30). The summed stress score was an important predictor of cardiac death; the
      hazard ratio was 1.2 (95% CI 1.07-1.34) per one-unit increment. CONCLUSIONS:
      Dobutamine-atropine stress myocardial perfusion imaging provides additional
      prognostic information incremental to clinical data in patients with diabetes who
      are unable to undergo exercise stress testing.

PMID- 12196441
TI  - Treatment of type 2 diabetes: the American Association of Clinical
      Endocrinologists Meeting, May 2002.

PMID- 12196442
TI  - Lifestyles matter in the prevention of type 2 diabetes.

PMID- 12196443
TI  - Wheat bran, whole grain, and food synergy.

PMID- 12196444
TI  - Subspecialist care improves diabetes outcomes.

PMID- 12196445
TI  - Defining and understanding "co-management" care.

PMID- 12196446
TI  - Severe hypoglycemia from clarithromycin-sulfonylurea drug interaction.

PMID- 12196447
TI  - The role of dobutamine stress echocardiography in detecting severe coronary
      artery disease in asymptomatic at high risk type 2 diabetic patients.

PMID- 12196448
TI  - Impairment of visual evoked potentials: an early central manifestation of
      diabetic neuropathy?

PMID- 12196449
TI  - Do latent autoimmune diabetes of the adult (LADA) patients require insulin at
      diagnosis?: response to Pozzilli and Di Mario.

PMID- 12196450
TI  - Pediatric use of insulin pumps: longer infusion site lifetime with NovoLog.

PMID- 12196451
TI  - Mortality in concurrent type 1 diabetes and anorexia nervosa.

PMID- 12196452
TI  - A case showing complete insulin independence after severe diabetic ketoacidosis
      associated with tacrolimus treatment.

PMID- 12196453
TI  - Elevated serum concentration of adipose-derived factor, adiponectin, in patients
      with type 1 diabetes.

PMID- 12196454
TI  - Not all long-acting insulins are the same.

PMID- 12196456
TI  - Response to Montori et al. Post-transplantation diabetes (PTD), risk factors for
      its development, prognostic implications, and optimal management of the disease.

PMID- 12196457
TI  - The succinate mechanism of insulin release.
AB  - Nutrient secretagogues can increase the production of succinyl-CoA in rat
      pancreatic islets. When succinate esters are the secretagogue, succinyl-CoA can
      be generated via the succinate thiokinase reaction. Other secretagogues can
      increase production of succinyl-CoA secondary to increasing alpha-ketoglutarate
      production by glutamate dehydrogenase or mitochondrial aspartate aminotransferase
      followed by the alpha-ketoglutarate dehydrogenase reaction. Although
      secretagogues can increase the production of succinyl-CoA, they do not increase
      the level of this metabolite until after they decrease the level of 3-hydroxy-3
      methylglutaryl-CoA (HMG-CoA). This suggests that the generated succinyl-CoA
      initially reacts with acetoacetate to yield acetoacetyl-CoA plus succinate in the
      succinyl-CoA-acetoacetate transferase reaction. This would be followed by
      acetoacetyl-CoA reacting with acetyl-CoA to generate HMG-CoA in the HMG-CoA
      synthetase reaction. HMG-CoA will then be reduced by NADPH to mevalonate in the
      HMG-CoA reductase reaction and/or cleaved to acetoacetate plus acetyl-CoA by HMG
      cleavage enzyme. Succinate derived from either exogenous succinate esters or
      generated by succinyl-CoA-acetoacetate transferase is metabolized to malate
      followed by the malic enzyme reaction. Increased production of NADPH by the
      latter reaction then increases reduction of HMG-CoA and accounts for the decrease
      in the level of HMG-CoA produced by secretagogues. Pyruvate carboxylation
      catalyzed by pyruvate carboxylase will supply oxaloacetate to mitochondrial
      aspartate aminotransferase. This would enable this aminotransferase to supply
      alpha-ketoglutarate to the alpha-ketoglutarate dehydrogenase complex and would,
      in part, account for secretagogues increasing the islet level of succinyl-CoA
      after they decrease the level of HMG-CoA. Mevalonate could be a trigger of
      insulin release as a result of its ability to alter membrane proteins and/or
      cytosolic Ca(2+). This is consistent with the fact that insulin secretagogues
      decrease the level of the mevalonate precursor HMG-CoA. In addition, inhibitors
      of HMG-CoA reductase interfere with insulin release and this inhibition can be
      reversed by mevalonate.

PMID- 12196458
TI  - Long-term treatment with dipeptidyl peptidase IV inhibitor improves hepatic and
      peripheral insulin sensitivity in the VDF Zucker rat: a euglycemic
      hyperinsulinemic clamp study.
AB  - Upon release into circulation, the potent insulin secretagogues glucose-dependent
      insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) are rapidly
      cleaved and inactivated by the enzyme dipeptidyl peptidase IV (DP IV). Long-term
      administration of specific DP IV inhibitors, so as to enhance circulating active
      GIP and GLP-1 levels, has been shown to improve glucose tolerance and beta-cell
      glucose responsiveness and to reduce hyperinsulinemia in the Vancouver diabetic
      fatty (VDF) rat model of type 2 diabetes. Using the VDF model, the current study
      was undertaken to examine the effects of long-term DP IV inhibitor treatment on
      insulin sensitivity. Euglycemic-hyperinsulinemic clamps were performed on two
      sets of conscious VDF rats treated with or without the DP IV inhibitor P32/98 (20
      mg. kg(-1). day(-1) for 12 weeks). The protocol consisted of three sequential 90
      min periods with insulin infusion rates of 0, 5, and 15 mU. kg(-1). min(-1) and
      included a constant infusion of [ (3)H]glucose for measure of hepatic and
      peripheral insulin sensitivity. Relative to untreated littermates, the treated
      animals showed a left shift in the sensitivity of hepatic glucose output to
      insulin (average reduction approximately 6 micro mol. kg(-1). min(-1)) and a
      marked gain in peripheral responsiveness to insulin, with glucose disposal rates
      increasing 105 and 216% in response to the two insulin steps (versus 2 and 46% in
      controls). These results provide the first demonstration of improved hepatic and
      peripheral insulin sensitivity after DP IV inhibitor therapy, and coupled with
      apparent improvements in beta-cell function, they offer strong support for the
      utility of these compounds in the treatment of diabetes.

PMID- 12196459
TI  - Regulation of dietary fatty acid entrapment in subcutaneous adipose tissue and
      skeletal muscle.
AB  - Using stable isotopic labeling of dietary fatty acids in conjunction with
      arteriovenous difference measurements, we have assessed the regulation of
      lipoprotein lipase-derived fatty acid entrapment in subcutaneous adipose tissue
      and forearm muscle in healthy subjects in the postprandial state. Eight
      volunteers fasted overnight and were then given a mixed meal containing [ 1
      (13)C]palmitic acid and [1-(13)C]oleic acid. At baseline and for 6 h after the
      meal, blood samples were obtained from an arterialized hand vein and veins
      draining subcutaneous abdominal adipose tissue and forearm muscle, and
      arteriovenous differences were calculated. Entrapment of labeled fatty acids
      released by circulating triacylglycerol hydrolysis was close to 100% at 60 min,
      decreasing to 10-30% by 360 min. Entrapment of labeled fatty acids in forearm
      muscle was >100% and did not change with time. This study shows that entrapment
      of dietary fatty acids in adipose tissue in the postprandial period is a highly
      regulated process (varying with time) and that this can be studied in humans
      using stable isotope- labeled fatty acids in combination with measurement of
      appropriate arteriovenous differences. Also, fatty acid trapping in skeletal
      muscle is fundamentally different from that in adipose tissue, in that all the
      fatty acids released by lipoprotein lipase in skeletal muscle are taken up by the
      tissue.

PMID- 12196460
TI  - Troglitazone treatment increases protein kinase B phosphorylation in skeletal
      muscle of normoglycemic subjects at risk for the development of type 2 diabetes.
AB  - We investigated whether the effect of troglitazone on glucose disposal is
      associated with altered insulin signaling. Nondiabetic first-degree relatives of
      type 2 diabetic patients (age 30 +/- 2 years, BMI 30 +/- 1 kg/m(2); n = 20) were
      randomized in a double-blind manner to 3 months of troglitazone (200 mg/day) or
      placebo treatment. Before and after treatment, 3-h euglycemic-hyperinsulinemic
      glucose clamps (40 mU. m(-2). min(-1)) were performed, and muscle biopsies were
      obtained immediately before and after the clamps. In the biopsies, insulin
      receptor kinase (IRK) activity, insulin receptor substrate (IRS)-1-associated
      phosphatidylinositol 3-kinase (PI3K) activity, Ser(473) and Thr(308)
      phosphorylation of protein kinase B (PKB), and protein expression of IRS-1, IRS
      2, phosphoinositol-dependent kinase-1 (PDK-1), PKB, and GLUT-4 were determined.
      After troglitazone treatment, insulin-stimulated glucose disposal was increased
      compared with pretreatment and placebo (279 +/- 37 vs. 211 +/- 26 and 200 +/- 25
      mg. m(-2). min(-1); both P < 0.05). IRK and PI3K activities were not altered by
      troglitazone, but PKB Ser(473) phosphorylation was enhanced compared with
      pretreatment and placebo at the clamp insulin level (138 +/- 36 vs. 77 +/- 16 and
      55 +/- 13 internal standard units; both P < 0.05) and with pretreatment at the
      basal level (31 +/- 9 vs. 14 +/- 4 internal standard units; P < 0.05). PKB
      Thr(308) phosphorylation also tended to be higher, but this was not statistically
      significant. Troglitazone did not alter insulin receptor number or IRS-1, IRS-2,
      PKB, PDK-1, or GLUT-4 protein expression. We conclude that increased PKB
      phosphorylation may contribute to the insulin-sensitizing effects of
      thiazolidinediones in human skeletal muscle.

PMID- 12196461
TI  - Muscle glucose uptake does not increase when only local arterial glucose
      concentration is increased.
AB  - Published models of mammalian whole-body glucose metabolism generally assume that
      glucose uptake is proportional to circulating glucose concentration at constant
      insulin concentration. One widely used model labels the increased whole-body
      glucose uptake seen with increased venous glucose concentration as "glucose
      effectiveness." In 1956 and 1957, we found on average no change in forearm
      glucose uptake when we doubled, or more than doubled, local forearm arterial
      glucose concentration by close arterial infusion so that pancreatic arterial
      glucose concentration did not change. These experiments are being reported in
      extenso for the first time. Since that time, two other groups have found in
      glucose/insulin clamp experiments that whole-body glucose uptake was not
      proportional to hyperglycemic concentrations, although uptake did increase. It
      was hypothesized that perhaps some organs and tissues do increase uptake
      proportionally and other tissues not at all. Our results show that skeletal
      muscle is a tissue in which glucose uptake, at constant insulin, is not changed
      acutely by hyperglycemia; there is no forearm glucose effectiveness. We suppose
      that this constancy occurs because there are so few GLUTs on the sarcolemma
      surface in the basal state and that they are saturated even at euglycemia. We
      also report earlier experiments from 1954 to 1955 in which comparable
      hyperglycemia was reached by a large oral dose of glucose, with a 10-fold
      increase in glucose uptake. The arterial glucose time curve during hyperglycemia
      was 20-30 mg/dl higher than the forearm venous curve.

PMID- 12196462
TI  - Isoform-specific regulation of 5' AMP-activated protein kinase in skeletal muscle
      from obese Zucker (fa/fa) rats in response to contraction.
AB  - Glucose transport can be activated in skeletal muscle in response to insulin via
      activation of phosphoinositide (PI) 3-kinase and in response to contractions or
      hypoxia, presumably via activation of 5' AMP-activated protein kinase (AMPK). We
      determined the effects of insulin and muscle contraction/hypoxia on PI 3-kinase,
      AMPK, and glucose transport activity in epitrochlearis skeletal muscle from
      insulin-resistant Zucker (fa/ fa) rats. Insulin-stimulated glucose transport in
      isolated skeletal muscle was reduced 47% in obese versus lean rats, with a
      parallel 42% reduction in tyrosine-associated PI 3-kinase activity. Contraction
      and hypoxia elicited normal responses for glucose transport in skeletal muscle
      from insulin-resistant obese rats. Isoform-specific AMPK activity was measured in
      skeletal muscle in response to insulin, contraction, or hypoxia. Contraction
      increased AMPKalpha1 activity 2.3-fold in lean rats, whereas no effect was noted
      in obese rats. Hypoxia increased AMPKalpha1 activity to a similar extent (more
      than sixfold) in lean and obese rats. Regardless of genotype, contraction, and
      hypoxia, each increased AMPKalpha2 activity more than fivefold, whereas insulin
      did not alter either AMPKalpha1 or -alpha2 activity in skeletal muscle. In
      conclusion, obesity-related insulin resistance is associated with an isoform
      specific impairment in AMPKalpha1 in response to contraction. However, this
      impairment does not appear to affect contraction-stimulated glucose transport.
      Activation of AMPKalpha2 in response to muscle contraction/ exercise is
      associated with a parallel and normal increase in glucose transport in insulin
      resistant skeletal muscle.

PMID- 12196463
TI  - Expression of connective tissue growth factor is increased in injured myocardium
      associated with protein kinase C beta2 activation and diabetes.
AB  - Protein kinase C (PKC) beta isoform activity is increased in myocardium of
      diabetic rodents and heart failure patients. Transgenic mice overexpressing
      PKCbeta2 (PKCbeta2Tg) in the myocardium exhibit cardiomyopathy and cardiac
      fibrosis. In this study, we characterized the expression of connective tissue
      growth factor (CTGF) and transforming growth factor beta (TGFbeta) with the
      development of fibrosis in heart from PKCbeta2Tg mice at 4-16 weeks of age. Heart
      to-body weight ratios of transgenic mice increased at 8 and 12 weeks, indicating
      hypertrophy, and ratios did not differ at 16 weeks. Collagen VI and fibronectin
      mRNA expression increased in PKCbeta2Tg hearts at 4-12 weeks. Histological
      examination revealed myocyte hypertrophy and fibrosis in 4- to 16-week PKCbeta2Tg
      hearts. CTGF expression increased in PKCbeta2Tg hearts at all ages, whereas
      TGFbeta increased only at 8 and 12 weeks. In 8-week diabetic mouse heart, CTGF
      and TGFbeta expression increased two- and fourfold, respectively. Similarly, CTGF
      expression increased in rat hearts at 2-8 weeks of diabetes. This is the first
      report of increased CTGF expression in myocardium of diabetic rodents suggesting
      that cardiac injury associated with PKCbeta2 activation, diabetes, or heart
      failure is marked by increased CTGF expression. CTGF could act independently or
      together with other cytokines to induce cardiac fibrosis and dysfunction.

PMID- 12196464
TI  - Need for GLUT4 activation to reach maximum effect of insulin-mediated glucose
      uptake in brown adipocytes isolated from GLUT4myc-expressing mice.
AB  - There is a need to understand whether the amount of GLUT4 at the cell surface
      determines the extent of glucose uptake in response to insulin. Thus, we created
      a heterozygous mouse expressing modest levels of myc-tagged GLUT4 (GLUT4myc) in
      insulin-sensitive tissues under the control of the human GLUT4 promoter. Insulin
      stimulated 2-deoxyglucose uptake 6.5-fold in isolated brown adipocytes. GLUT1 did
      not contribute to the insulin response. The stimulation by insulin was completely
      blocked by wortmannin and partly (55 +/- 2%) by the p38 mitogen-activated protein
      kinase (MAPK) inhibitor SB203580. Insulin increased surface exposure of GLUT4myc
      twofold (determined by fluorescent or enzyme-linked myc immunodetection in intact
      adipocytes). Such increase was completely blocked by wortmannin but insensitive
      to SB203580. Insulin increased the kinase activity of the p38 MAPK beta-isoform
      1.9-fold without affecting p38-alpha. In summary, the GLUT4myc mouse is a
      promising model for measuring GLUT4 translocation in intact primary cells. It
      affords direct comparison between GLUT4 translocation and glucose uptake in
      similar cell preparations, allowing one to study the regulation of GLUT4
      activity. Using this animal model, we found that stimulation of glucose uptake
      into brown adipocytes involves both GLUT4 translocation and activation.

PMID- 12196465
TI  - Transplantation of adipose tissue lacking leptin is unable to reverse the
      metabolic abnormalities associated with lipoatrophy.
AB  - Severe adipose tissue deficiency (lipoatrophy) causes insulin-resistant diabetes,
      elevated serum triglyceride and fatty acid levels, and massive triglyceride
      deposition in the liver. In lipoatrophic A-ZIP/F-1 mice, transplantation of
      normal adipose tissue greatly improved these parameters, whereas 1 week of leptin
      infusion had more modest effects. In contrast, leptin infusion was strikingly
      more effective in the aP2-n sterol response element binding protein 1
      lipoatrophic mouse. Here we show that a longer duration of leptin infusion
      further improves the metabolic status of the A-ZIP/F-1 mice and that genetic
      background does not make a major contribution to the effect of leptin on glucose
      and insulin levels. Adipose transplantation using leptin-deficient ob/ob fat had
      no effect on the phenotype of the A-ZIP/F-1 mice. Moreover, the presence of ob/ob
      adipose tissue did not enhance the effects of leptin infusion. Serum adiponectin
      levels were 2% of control levels in the A-ZIP/F-1 mouse and increased only
      twofold with adipose transplantation and not at all after leptin infusion,
      suggesting that adiponectin deficiency is not a major contributor to the diabetic
      phenotype. Taken together, these results suggest that sequestration of
      triglycerides into fat may not be enough to restore a nondiabetic phenotype and
      that leptin deficiency plays a major role in causing the metabolic complications
      of lipoatrophy.

PMID- 12196466
TI  - Androgens decrease plasma adiponectin, an insulin-sensitizing adipocyte-derived
      protein.
AB  - Adiponectin, an adipose-specific secretory protein, exhibits antidiabetic and
      antiatherogenic properties. In the present study, we examined the effects of sex
      hormones on the regulation of adiponectin production. Plasma adiponectin
      concentrations were significantly lower in 442 men (age, 52.6 +/- 11.9 years
      [mean +/- SD]) than in 137 women (53.2 +/- 12.0 years) but not different between
      pre- and postmenopausal women. In mice, ovariectomy did not alter plasma
      adiponectin levels. In contrast, high levels of plasma adiponectin were found in
      castrated mice. Testosterone treatment reduced plasma adiponectin concentration
      in both sham-operated and castrated mice. In 3T3-L1 adipocytes, testosterone
      reduced adiponectin secretion into the culture media, using pulse-chase study.
      Castration-induced increase in plasma adiponectin was associated with a
      significant improvement of insulin sensitivity. Our results indicate that
      androgens decrease plasma adiponectin and that androgen-induced
      hypoadiponectinemia may be related to the high risks of insulin resistance and
      atherosclerosis in men.

PMID- 12196467
TI  - Delayed transcapillary transport of insulin to muscle interstitial fluid in obese
      subjects.
AB  - Insulin-resistant subjects have a slow onset of insulin action, and the
      underlying mechanism has not been determined. To evaluate whether a delayed
      transcapillary transport is part of the peripheral insulin resistance, we
      followed the kinetics of infused insulin and inulin in plasma and muscle
      interstitial fluid in obese insulin-resistant patients and control subjects. A
      total of 10 lean and 10 obese men (BMI 24 +/- 0.8 vs. 32 +/- 0.8 kg/m(2), P <
      0.001) was evaluated during a hyperinsulinemic-euglycemic clamp (insulin infusion
      rate 120 mU. m(-2). min(-1)) combined with an inulin infusion. Measurements of
      insulin and inulin in plasma were taken by means of arterial-venous
      catheterization of the forearm and microdialysis in brachioradialis muscle
      combined with forearm blood flow measurements with vein occlusion pletysmography.
      The obese subjects had a significantly lower steady-state glucose infusion rate
      and, moreover, demonstrated a delayed appearance of insulin (time to achieve half
      maximal concentration [T(1/2)] 72 +/- 6 vs. 46 +/- 6 min in control subjects, P <
      0.05) as well as inulin (T(1/2) 83 +/- 3 vs. 53 +/- 7 min, P < 0.01) in the
      interstitial fluid. Also, the obese subjects had a delayed onset of insulin
      action (T(1/2) 70 +/- 9 vs. 45 +/- 5 min in control subjects, P < 0.05), and
      their forearm blood flow rate was significantly lower. These results demonstrate
      a delayed transcapillary transport of insulin and inulin from plasma to the
      muscle interstitial fluid and a delayed onset of insulin action in insulin
      resistant obese subjects.

PMID- 12196468
TI  - Role of ATP production and uncoupling protein-2 in the insulin secretory defect
      induced by chronic exposure to high glucose or free fatty acids and effects of
      peroxisome proliferator-activated receptor-gamma inhibition.
AB  - In rat pancreatic islets chronically exposed to high glucose or high free fatty
      acid (FFA) levels, glucose-induced insulin release and mitochondrial glucose
      oxidation are impaired. These abnormalities are associated with high basal ATP
      levels but a decreased glucose-induced ATP production (Delta of increment over
      baseline 0.7 +/- 0.5 or 0.5 +/- 0.3 pmol/islet in islets exposed to glucose or
      FFA vs. 12.0 +/- 0.6 in control islets, n = 3; P < 0.01) and, as a consequence,
      with an altered ATP/ADP ratio. To investigate further the mechanism of the
      impaired ATP formation, we measured in rat pancreatic islets glucose-stimulated
      pyruvate dehydrogenase (PDH) activity, a key enzyme for pyruvate metabolism and
      for the subsequent glucose oxidation through the Krebs cycle, and also the
      uncoupling protein-2 (UCP-2) content by Western blot. In islets exposed to high
      glucose or FFA, glucose-stimulated PDH activity was impaired and UCP-2 was
      overexpressed. Because UCP-2 expression is modulated by a peroxisome proliferator
      activated receptor (PPAR)-dependent pathway, we measured PPAR-gamma contents by
      Western blot and the effects of a PPAR-gamma antagonist. PPAR-gamma levels were
      overexpressed in islets cultured with high FFA levels but unaffected in islets
      exposed to high glucose. In islets exposed to high FFA concentration, a PPAR
      gamma antagonist was able to prevent UCP-2 overexpression and to restore insulin
      secretion and the ATP/ADP ratio. These data indicate that in rat pancreatic
      islets chronically exposed to high glucose or FFA, glucose-induced impairment of
      insulin secretion is associated with (and might be due to) altered mitochondrial
      function, which results in impaired glucose oxidation, overexpression of the UCP
      2 protein, and a consequent decrease of ATP production. This alteration in FFA
      cultured islets is mediated by the PPAR-gamma pathway.

PMID- 12196469
TI  - Glucose-sensing in glucagon-like peptide-1-secreting cells.
AB  - Glucagon-like peptide-1 (GLP-1) is released from intestinal L-cells in response
      to carbohydrate and fat in the diet. Despite the interest in GLP-1 as an
      antidiabetic agent, very little is known about the mechanism of stimulus
      secretion coupling in L-cells. We investigated the electrophysiological events
      underlying glucose-induced GLP-1 release in the GLP-1-secreting cell line,
      GLUTag. Cells were studied using perforated-patch and standard whole-cell patch
      clamp recordings. GLUTag cells were largely quiescent and hyperpolarized in the
      absence of glucose. Increasing the glucose concentration between 0 and 20 mmol/l
      decreased the membrane conductance, caused membrane depolarization, and triggered
      the generation of action potentials. Action potentials were also triggered by
      tolbutamide (500 micro mol/l) and were suppressed by diazoxide (340 micro mol/l)
      or the metabolic inhibitor azide (3 mmol/l), suggesting an involvement of K(ATP)
      channels. Large tolbutamide-sensitive washout currents developed in standard
      whole-cell recordings, confirming the presence of K(ATP) channels. RT-PCR
      detected the K(ATP) channel subunits Kir6.2 and SUR1 and glucokinase. GLP-1
      secretion was also stimulated by glucose over the concentration range 0-25 mmol/l
      and by tolbutamide. Our results suggest that glucose triggers GLP-1 release
      through closure of K(ATP) channels and action potential generation.

PMID- 12196470
TI  - Modulation of glucocorticoid-induced GAD expression in pancreatic beta-cells by
      transcriptional activation of the GAD67 promoter and its possible effect on the
      development of diabetes.
AB  - GAD is a pancreatic beta-cell autoantigen in humans and nonobese diabetic (NOD)
      mice. Modulation of GAD expression in pancreatic beta-cells has been suggested to
      be associated with the development of autoimmune diabetes. Hormonal changes
      through environmental stimuli are considered to influence the expression of the
      disease. We determined whether steroid hormones would modulate the expression of
      GAD in pancreatic beta-cells. We treated NOD mouse beta-cells (MIN6N8a cells)
      with various steroids, including testosterone, estradiol, progesterone, and
      cortisol, and examined the expression of GAD67 mRNA. We found that only cortisol
      enhanced the expression of GAD67, whereas the other steroid hormones had no
      effect. When we treated MIN6N8a cells with a synthetic glucocorticoid,
      dexamethasone, we found that GAD67 mRNA expression was stimulated in a dose- and
      time-dependent manner. Cells treated with 100 nmol/l dexamethasone for 6 h showed
      a 10-fold increase in the expression of GAD67 mRNA and an increase in GAD67
      protein. The upregulation of GAD67 expression in beta-cells by dexamethasone was
      found to be due to the transcriptional activation of the GAD67 promoter. We then
      examined whether dexamethasone would influence the development of diabetes in NOD
      mice. Injection of dexamethasone into neonatal NOD mice resulted in a significant
      increase in the expression of GAD67 mRNA in pancreatic beta-cells and the
      development of insulitis and diabetes. We conclude that glucocorticoid hormones
      can modulate GAD expression by the transcriptional activation of the GAD promoter
      and may influence the development of autoimmune diabetes in NOD mice.

PMID- 12196471
TI  - Plasma membrane Ca(2+)-ATPase overexpression reduces Ca(2+) oscillations and
      increases insulin release induced by glucose in insulin-secreting BRIN-BD11
      cells.
AB  - In the mouse beta-cell, glucose generates large amplitude oscillations of the
      cytosolic-free Ca(2+) concentration ([Ca(2+)](i)) that are synchronous to insulin
      release oscillations. To examine the role played by [ Ca(2+)](i) oscillations in
      the process of insulin release, we examined the effect of plasma membrane Ca(2+)
      ATPase (PMCA) overexpression on glucose-induced Ca(2+) oscillations and insulin
      release in BRIN-BD11 cells. BRIN-BD11 cells were stably transfected with PMCA2wb.
      Overexpression could be assessed at the mRNA and protein level, with appropriate
      targeting to the plasma membrane assessed by immunofluorescence and the increase
      in PMCA activity. In response to K(+), overexpressing cells showed a markedly
      reduced rise in [Ca(2+)](i). In response to glucose, control cells showed large
      amplitude [Ca(2+)](i) oscillations, whereas overexpressing cells showed markedly
      reduced increases in [Ca(2+)](i) without such large oscillations. Suppression of
      [Ca(2+)](i) oscillations was accompanied by an increase in glucose metabolism and
      insulin release that remained oscillatory despite having a lower periodicity.
      Hence, [Ca(2+)] (i) oscillations appear unnecessary for glucose-induced insulin
      release and may even be less favorable than a stable increase in [ Ca(2+)](i) for
      optimal hormone secretion. [Ca(2+)](i) oscillations do not directly drive insulin
      release oscillations but may nevertheless intervene in the fine regulation of
      such oscillations.

PMID- 12196472
TI  - Differential interactions of nateglinide and repaglinide on the human beta-cell
      sulphonylurea receptor 1.
AB  - Repaglinide and nateglinide represent a new class of insulin secretagogues,
      structurally unrelated to sulphonylureas, that were developed for the treatment
      of type 2 diabetes. The inhibitory effect of these drugs was investigated on
      recombinant wild-type and mutant Kir6.2/SUR1 channels expressed in HEK293 cells.
      Nateglinide and repaglinide dose-dependently inhibited whole-cell Kir6.2/SUR1
      currents with half-maximal inhibitory concentration (IC(50)) values of 800 and 21
      nmol/l, respectively. Mutation of serine 1237 in SUR1 to tyrosine (S1237Y)
      abolished tolbutamide and nateglinide block, suggesting that these drugs share a
      common point of interaction on the SUR1 subunit of the ATP-sensitive K(+)
      channel. In contrast, repaglinide inhibition was unaffected by the S1237Y
      mutation (IC(50) = 23 nmol/l). Radioligand binding studies revealed a single high
      affinity binding site for [(3)H]repaglinide on membranes prepared from HEK293
      cells expressing wild-type (equilibrium dissociation constant [K(D)] = 0.40
      nmol/l) or mutant (K(D) = 0.31 nmol/l) Kir6.2/SUR1 channels. Nateglinide and
      tolbutamide displaced [(3)H]repaglinide binding to wild-type channels with IC(50)
      values of 0.7 and 26 micro mol/l, respectively, but produced <10% displacement of
      [(3)H]repaglinide bound to mutant channels. This is consistent with the idea that
      binding of nateglinide and tolbutamide, but not repaglinide, is abolished by the
      SUR1[S1237Y] mutation and that the binding site for repaglinide is not identical
      to that of nateglinde/tolbutamide. These results are discussed in terms of a
      conformational analysis of the drug molecules.

PMID- 12196473
TI  - Preservation of pancreatic beta-cell function and prevention of type 2 diabetes
      by pharmacological treatment of insulin resistance in high-risk hispanic women.
AB  - Type 2 diabetes frequently results from progressive failure of pancreatic beta
      cell function in the presence of chronic insulin resistance. We tested whether
      chronic amelioration of insulin resistance would preserve pancreatic beta-cell
      function and delay or prevent the onset of type 2 diabetes in high-risk Hispanic
      women. Women with previous gestational diabetes were randomized to placebo (n =
      133) or the insulin-sensitizing drug troglitazone (400 mg/day; n = 133)
      administered in double-blind fashion. Fasting plasma glucose was measured every 3
      months, and oral glucose tolerance tests (OGTTs) were performed annually to
      detect diabetes. Intravenous glucose tolerance tests (IVGTTs) were performed at
      baseline and 3 months later to identify early metabolic changes associated with
      any protection from diabetes. Women who did not develop diabetes during the trial
      returned for OGTTs and IVGTTs 8 months after study medications were stopped.
      During a median follow-up of 30 months on blinded medication, average annual
      diabetes incidence rates in the 236 women who returned for at least one follow-up
      visit were 12.1 and 5.4% in women assigned to placebo and troglitazone,
      respectively (P < 0.01). Protection from diabetes in the troglitazone group 1)
      was closely related to the degree of reduction in endogenous insulin requirements
      3 months after randomization, 2) persisted 8 months after study medications were
      stopped, and 3) was associated with preservation of beta-cell compensation for
      insulin resistance. Treatment with troglitazone delayed or prevented the onset of
      type 2 diabetes in high-risk Hispanic women. The protective effect was associated
      with the preservation of pancreatic beta-cell function and appeared to be
      mediated by a reduction in the secretory demands placed on beta-cells by chronic
      insulin resistance.

PMID- 12196474
TI  - Diacylglycerol production and protein kinase C activity are increased in a mouse
      model of diabetic embryopathy.
AB  - Activation of the diacylglycerol-protein kinase C (DAG-PKC) cascade by excess
      glucose has been implicated in vascular complications of diabetes. Its
      involvement in diabetic embryopathy has not been established. We examined DAG
      production and PKC activities in embryos and decidua of streptozotocin (STZ)
      diabetic or transiently hyperglycemic mice during neural tube formation. STZ
      diabetes significantly increased DAG and total PKC activity in decidua (1.5- and
      1.4-fold, respectively) and embryos (1.7- and 1.3-fold, respectively) on day 9.5.
      Membrane-associated PKC alpha, betaII, delta, and zeta were increased in decidua
      by 1.25- to 2.8-fold. Maternal hyperglycemia induced by glucose injection on day
      7.5, the day before the onset of neural tube formation, also increased DAG, PKC
      activity, and PKC isoforms (1.1-, 1.6-, and 1.5-fold, respectively) in the embryo
      on day 9.5. Notably, membrane-associated PKC activity was increased 24-fold in
      embryos of diabetic mice with structural defects. These data indicate that
      hyperglycemia just before organogenesis activates the DAG-PKC cascade and is
      correlated with congenital defects.

PMID- 12196475
TI  - Maternal diabetes increases the risk of caudal regression caused by retinoic
      acid.
AB  - Maternal diabetes increases the risk of congenital malformations in the offspring
      of affected pregnancies. This increase arises from the teratogenic effect of the
      maternal diabetic milieu on the developing embryo, although the mechanism of this
      action is poorly understood. In the present study, we examined whether the
      vitamin A metabolite retinoic acid (RA), a common drug with well-known
      teratogenic properties, may interact with maternal diabetes to alter the
      incidence of congenital malformations in mice. Our results show that when treated
      with RA, embryos of diabetic mice are significantly more prone than embryos of
      nondiabetic mice to develop caudal regression, a defect that is highly associated
      with diabetic pregnancy in humans. By studying the vestigial tail (Wnt-3a(vt))
      mutant, we provide evidence that Wnt-3a, a gene that controls the development of
      the caudal region, is directly involved in the pathogenic pathway of RA-induced
      caudal regression. We further show that the molecular basis of the increased
      susceptibility of embryos of diabetic mice to RA involves enhanced downregulation
      of Wnt-3a expression. This positive interaction between RA and maternal diabetes
      may have implications for humans in suggesting increased susceptibility to
      environmental teratogens during diabetic pregnancy.

PMID- 12196476
TI  - Nitrosative stress, uric Acid, and peripheral nerve function in early type 1
      diabetes.
AB  - The present study was performed to determine whether nitric oxide overproduction
      is associated with deterioration in peripheral nerve function in type 1 diabetes.
      We measured peripheral nerve function and biochemical indicators of nitrosative
      stress annually for 3 years in 37 patients with type 1 diabetes. Plasma nitrite
      and nitrate (collectively NO(x)) were 34.0 +/- 4.9 micro mol/l in the control
      subjects and 52.4 +/- 5.1, 50.0 +/- 5.1, and 49.0 +/- 5.2 in the diabetic
      patients at the first, second, and third evaluations, respectively (P < 0.01).
      Nitrotyrosine (NTY) was 13.3 +/- 2.0 micro mol/l in the control subjects and 26.8
      +/- 4.4, 26.1 +/- 4.3, and 32.7 +/- 4.3 in the diabetic patients (P < 0.01). Uric
      acid was suppressed by 20% in the diabetic patients (P < 0.001). Composite motor
      nerve conduction velocity for the median, ulnar, and peroneal nerves was
      decreased in patients with high versus low NTY (mean Z score -0.522 +/- 0.25
      versus 0.273 +/- 0.22; P < 0.025). Patients with high NO(x) had decreased
      sweating, and those with suppressed uric acid had decreased autonomic function.
      In conclusion, nitrosative stress in early diabetes is associated with suppressed
      uric acid and deterioration in peripheral nerve function.

PMID- 12196478
TI  - Peroxynitrite induces formation of N( epsilon )-(carboxymethyl) lysine by the
      cleavage of Amadori product and generation of glucosone and glyoxal from glucose:
      novel pathways for protein modification by peroxynitrite.
AB  - Accumulation of advanced glycation end products (AGEs) on tissue proteins
      increases with pathogenesis of diabetic complications and atherosclerosis. Here
      we examined the effect of peroxynitrite (ONOO(-)) on the formation of N( epsilon
      )-(carboxymethyl)lysine (CML), a major AGE-structure. When glycated human serum
      albumin (HSA; Amadori-modified protein) was incubated with ONOO(-), CML formation
      was detected by both enzyme-linked immunosorbent assay and high-performance
      liquid chromatography (HPLC) and increased with increasing ONOO(-)
      concentrations. CML was also formed when glucose, preincubated with ONOO(-), was
      incubated with HSA but was completely inhibited by aminoguanidine, a trapping
      reagent for alpha-oxoaldehydes. For identifying the aldehydes that contributed to
      ONOO(-)-induced CML formation, glucose was incubated with ONOO(-) in the presence
      of 2,3-diaminonaphthalene. This experiment led to identification of glucosone and
      glyoxal by HPLC. Our results provide the first evidence that ONOO(-) can induce
      protein modification by oxidative cleavage of the Amadori product and also by
      generation of reactive alpha-oxoaldehydes from glucose.

PMID- 12196477
TI  - The AGE inhibitor pyridoxamine inhibits development of retinopathy in
      experimental diabetes.
AB  - We examined the ability of pyridoxamine (PM), an inhibitor of formation of
      advanced glycation end products (AGEs) and lipoxidation end products (ALEs), to
      protect against diabetes-induced retinal vascular lesions. The effects of PM were
      compared with the antioxidants vitamin E (VE) and R-alpha-lipoic acid (LA) in
      streptozotocin-induced diabetic rats. Animals were given either PM (1 g/l
      drinking water), VE (2,000 IU/kg diet), or LA (0.05%/kg diet). After 29 weeks of
      diabetes, retinas were examined for pathogenic changes, alterations in
      extracellular matrix (ECM) gene expression, and accumulation of the
      immunoreactive AGE/ALE N( epsilon )-(carboxymethyl)lysine (CML). Acellular
      capillaries were increased more than threefold, accompanied by significant
      upregulation of laminin immunoreactivity in the retinal microvasculature.
      Diabetes also increased mRNA expression for fibronectin (2-fold), collagen IV
      (1.6-fold), and laminin beta chain (2.6-fold) in untreated diabetic rats compared
      with nondiabetic rats. PM treatment protected against capillary drop-out and
      limited laminin protein upregulation and ECM mRNA expression and the increase in
      CML in the retinal vasculature. VE and LA failed to protect against retinal
      capillary closure and had inconsistent effects on diabetes-related upregulation
      of ECM mRNAs. These results indicate that the AGE/ALE inhibitor PM protected
      against a range of pathological changes in the diabetic retina and may be useful
      for treating diabetic retinopathy.

PMID- 12196479
TI  - Type 1 and type 2 diabetic patients display different patterns of cellular
      microparticles.
AB  - The development of vasculopathies in diabetes involves multifactorial processes
      including pathological activation of vascular cells. Release of microparticles by
      activated cells has been reported in diseases associated with thrombotic risk,
      but few data are available in diabetes. The aim of the present work was to
      explore the number and the procoagulant activity of cell-derived microparticles
      in type 1 and 2 diabetic patients. Compared with age-matched control subjects,
      type 1 diabetic patients presented significantly higher numbers of platelet and
      endothelial microparticles (PMP and EMP), total annexin V-positive blood cell
      microparticles (TMP), and increased levels of TMP-associated procoagulant
      activity. In type 2 diabetic patients, only TMP levels were significantly higher
      without concomitant increase of their procoagulant activity. Interestingly, in
      type 1 diabetic patients, TMP procoagulant activity was correlated with HbA(1c),
      suggesting that procoagulant activity is associated with glucose imbalance. These
      results showed that a wide vesiculation process, resulting from activation or
      apoptosis of several cell types, occurs in diabetes. However, diabetic patients
      differ by the procoagulant activity and the cellular origin of microparticles. In
      type 1 diabetic patients, TMP-procoagulant activity could be involved in vascular
      complications. Moreover, its correlation with HbA(1c) reinforces the importance
      of an optimal glycemic control in type 1 diabetes.

PMID- 12196480
TI  - Augmentation of the neutrophil respiratory burst through the action of advanced
      glycation end products: a potential contributor to vascular oxidant stress.
AB  - An accelerated accumulation of advanced glycation end products (AGEs) occurs in
      diabetes secondary to the increased glycemic burden. In this study, we
      investigated the contribution of AGEs to intravascular oxidant stress by
      examining their action on the neutrophil burst of reactive oxygen species (ROS);
      this may be a significant donor to the overall vascular redox status and to
      vasculopathy. AGEs exerted a dose-dependent enhancement on the neutrophil
      respiratory burst in response to a secondary mechanical stimulus (up to 265 +/-
      42%, P = 0.022) or chemical stimulation with formyl-methylleucylphenylalanine 100
      nmol/l (up to 218 +/- 19%, P < 0.001), although they possessed no ability to
      augment the neutrophil respiratory burst alone. This phenomenon was both
      immediate and reversible and depended on the simultaneous presence of AGEs with
      the additional stimulus. It appeared to work through an upregulation of the
      neutrophil NADPH oxidase, the enzyme responsible for ROS generation, as seen by a
      diphenyleneiodonium-dependent suppression of basal and augmented ROS output.
      Moreover, this action of AGEs was found to be complementary to that of neutrophil
      priming agents, also known to upregulate neutrophil ROS production, implying the
      presence of distinct intracellular transduction pathways mediating the effect of
      these two classes of agents.

PMID- 12196481
TI  - The prevalent Glu23Lys polymorphism in the potassium inward rectifier 6.2
      (KIR6.2) gene is associated with impaired glucagon suppression in response to
      hyperglycemia.
AB  - Genetic factors play an important role in the pathogenesis of type 2 diabetes.
      The relevance to type 2 diabetes of the common polymorphism Glu23Lys in the
      potassium inward rectifier 6.2 (KIR6.2) gene is still controversial. The aim of
      this study was to assess whether this polymorphism influences beta-cell function,
      alpha-cell function, or insulin action. We therefore studied 298 nondiabetic
      subjects using an oral glucose tolerance test (OGTT) and 75 nondiabetic subjects
      using a hyperglycemic clamp (10 mmol/l) with additional glucagon-like peptide
      (GLP)-1 and arginine stimulation. The prevalence of the Lys allele was
      approximately 37%, and the Lys allele was associated with higher incremental
      plasma glucose during the OGTT (P = 0.03, ANOVA). Neither first- nor second-phase
      glucose-stimulated C-peptide secretion was affected by the presence of the
      polymorphism; nor were maximal glucose-, GLP-1-, or arginine-induced C-peptide
      secretion rates; nor was insulin sensitivity (all P > 0.7). However, the relative
      decrease in plasma glucagon concentrations during the 10 min after the glucose
      challenge was reduced in carriers of the Lys allele (10 +/- 3% decrease from
      baseline in Lys/Lys, 18 +/- 2% in Glu/Lys, and 20 +/- 2% in Glu/Glu; P = 0.01,
      ANOVA). In conclusion, our findings suggest that the common Glu23Lys polymorphism
      in KIR6.2 is not necessarily associated with beta-cell dysfunction or insulin
      resistance but with diminished suppression of glucagon secretion in response to
      hyperglycemia. Our findings thus confirm its functional relevance for glucose
      metabolism in humans.

PMID- 12196482
TI  - Liver pyruvate kinase polymorphisms are associated with type 2 diabetes in
      northern European Caucasians.
AB  - Pyruvate kinase is a key glycolytic enzyme. Isoforms that are expressed in the
      red cell, liver, pancreatic beta-cells, small intestine, and proximal renal
      tubule are encoded by the 12 exons of the PKLR gene, which maps to chromosome
      1q23. We hypothesized that common variants of the PKLR gene could account for the
      linkage of diabetes to this region. We screened the promoter regions, exons and
      surrounding introns, and the 3' untranslated region for mutations. We identified
      five single-nucleotide polymorphisms (SNPs), and only one (V506I, exon 11)
      altered the coding sequence. We tested the five SNPs, a poly-T insertion-deletion
      polymorphism, and an ATT triplet repeat in 131 unrelated diabetic patients and
      118 nondiabetic control subjects. The V506I variant was rare and not associated
      with type 2 diabetes. The four SNPs and the insertion-deletion polymorphism were
      associated with diabetes, with a 10% difference between individuals with diabetes
      and nondiabetic individuals (P = 0.001-0.011, relative risk for minor allele
      1.85). The same trend was found for the ATT repeat (P = 0.029). Common variants
      in the PKLR are associated with increased risk of type 2 diabetes, but because of
      strong linkage disequilibrium between variants, the actual susceptibility allele
      may be in a different gene.

PMID- 12196483
TI  - A comprehensive, statistically powered analysis of GAD2 in type 1 diabetes.
AB  - GAD2 maps to chromosome 10p11.23 and encodes the 65-kDa isoform of GAD65, a major
      autoantigen in type 1 diabetes. The genetic variation that influences expression
      of preproinsulin mRNA, encoding another major autoantigen in type 1 diabetes, has
      already been shown to be genetically associated with disease. Previous reports
      that have assessed the association of GAD2 with type 1 diabetes have not used a
      dense map of markers surrounding the gene and have relied on very small clinical
      sample sizes. Consequently, no definite conclusions can be drawn from their
      negative results. We have therefore systematically searched all exons, the 3'
      untranslated region (UTR), the 5' UTR, and the 5' upstream region of GAD2, for
      polymorphisms in 32 white European individuals. We have genotyped these
      polymorphisms in a maximum of 472 U.K. type 1 diabetic affected sib pair families
      exhibiting linkage to type 1 diabetes on chromosome 10p and have tested both
      single variants and haplotypes in the GAD2 region for association with disease.
      We subsequently followed up our results by genotyping a subset of these single
      nucleotide polymorphisms in a maximum of 873 Finnish families with at least one
      affected child. Our results suggest that GAD2 does not play a major role in type
      1 diabetes in these two European populations.

PMID- 12196484
TI  - Polymorphic susceptibility to the molecular causes of neural tube defects during
      diabetic embryopathy.
AB  - Previously, we demonstrated that neural tube defects (NTDs) are significantly
      increased in a mouse model of diabetic pregnancy. In addition, expression of Pax
      3, a gene encoding a transcription factor required for neural tube development,
      is significantly decreased. This suggests that diabetic embryopathy results from
      impaired expression of genes regulating essential morphogenetic processes. Here,
      we report that in one mouse strain, C57Bl/6J, embryos are resistant to the
      effects of maternal diabetes on NTDs and Pax-3 expression, in contrast to a
      susceptible strain, FVB, in which maternal diabetes significantly increases NTDs
      (P = 0.02) and inhibits Pax-3 expression (P = 0.01). Resistance to NTDs caused by
      diabetic pregnancy is a dominant trait, as demonstrated by heterozygous embryos
      of diabetic or nondiabetic mothers of either strain. There was no significant
      difference between strains in expression of genes that regulate free radical
      scavenging pathways, suggesting that susceptibility to oxidative stress does not
      account for the genetic differences. Understanding the genetic bases for
      differential susceptibility to altered gene expression and NTDs in diabetic mice
      may be important in delineating the mechanisms by which maternal hyperglycemia
      interferes with embryo gene expression. Moreover, if susceptibility to diabetic
      embryopathy is variable in humans as well as in mice, it may be possible to
      screen individuals at increased risk for this complication of diabetes.

PMID- 12196485
TI  - Is there an antiaging medicine?
AB  - In spite of considerable hype to the contrary, there is no convincing evidence
      that currently existing so-called "antiaging" remedies promoted by a variety of
      companies and other organizations can slow aging or increase longevity in humans.
      Nevertheless, a variety of experiments with laboratory animals indicate that
      aging rates and life expectancy can be altered. Research going back to the 1930s
      has shown that caloric restriction (also called dietary restriction) extends life
      expectancy by 30-40% in experimental animals, presumably at least partially by
      delaying the occurrence of age-dependent diseases. Mutations that decrease
      production of insulin growth factor I in laboratory mammals, and those that
      decrease insulin-like signaling in nematodes and fruit flies, have increased life
      expectancy as well. Other general strategies that appear promising include
      interventions that reduce oxidative stress and/or increase resistance to stress;
      hormone and cell replacement therapies may also have value in dealing with
      specific age-related pathologies. This article reports the findings of a
      consensus workshop that discussed what is known about existing and future
      interventions to slow, stop, or reverse aging in animals, and how these might be
      applied to humans through future research.

PMID- 12196486
TI  - Age-related differences in the effect of running training on cardiac Myosin
      isozyme composition in rats.
AB  - We examined the effect of running training on age-related changes in cardiac
      myosin isozyme composition in rats. Female Fischer 344 rats (6, 12, 20, and 27
      months old) were divided into two groups: sedentary control and trained. The
      trained group rats were trained by treadmill running for up to 60 minutes per
      day, 5 days per week for 8 weeks at up to 30 m per minute. In sedentary control
      rats, the proportion of V1 myosin, that is, alpha-myosin heavy chain (MyHC)
      isoform, decreased progressively from 6 to 27 months of age. In the younger age
      groups (6 or 12 months old), there was a shift from V1 myosin to V3 myosin (beta
      MyHC isoform) in trained hearts. However, the training program did not induce a
      cardiac myosin isozyme transition in older rats (20 or 27 months old). These
      results suggest that the mechanisms mediating the responses of cardiac muscle to
      running training alter during aging.

PMID- 12196488
TI  - Terrorism and aging.

PMID- 12196487
TI  - Ankle reflex stiffness during unperceived perturbation of standing in elderly
      subjects.
AB  - Postural reflex activity during unperceived perturbation of standing was
      investigated in 38 elderly subjects (70-96 years old) and 10 younger adults (19
      48 years old), and it was related in the elderly group to a history of
      unexplained falling in the 12 months prior to testing. Ankle torque (T) and ankle
      angle (A) were recorded during unperceived forward pulls to obtain the ankle
      stiffness (DeltaT/DeltaA), providing a measure of postural reflex activity at the
      ankle. Elderly nonfallers and younger adults had similar ranges of normalized
      ankle reflex stiffness. High ankle stiffness was significantly more common in
      elderly multiple fallers than in elderly nonfallers (p =.018). Furthermore, a
      majority of unstable elderly subjects who had reported a single unexplained fall
      also had unusually high ankle stiffness (p =.004). Multiple fallers and unstable
      subjects tended to overshoot backward on pull release in comparison with
      nonfallers (p =.003), which is suggestive of an overactive reflex response that
      might contribute to postural instability.

PMID- 12196489
TI  - Nutrition, exercise, and influenza vaccination.

PMID- 12196490
TI  - Exercise and psychosocial factors modulate immunity to influenza vaccine in
      elderly individuals.
AB  - BACKGROUND: Decreases in immune responsiveness with age contribute to the
      increased incidence and severity of infectious disease among elderly adults. The
      immune response to immunization also decreases with advancing age. Lifestyle
      factors (exercise, diet) have been established to play an important role in
      immunosenescence, and the practice of "healthy" behavior may minimize the age
      associated decline of immune function. The objective of this study was to
      determine whether exercise, diet, and psychosocial factors were associated with
      altered immune response to influenza vaccine. METHODS: Adults aged 62 years and
      older were categorized into one of three groups: active (> or =20 min vigorous
      exercise three or more times per week), moderately active (regular exercise but
      with less intensity, frequency, and/or duration), or sedentary (no exercise). Two
      weeks postimmunization, serum was frozen for antibody analysis, and peripheral
      blood mononuclear cells (PBMC) were cultured in vitro with influenza vaccine to
      elicit antigen-specific responses (proliferation and cytokine [IL-2, IFN-gamma,
      IL-10] production). Cytokines and antibody were measured by enzyme-linked
      immunosorbent assay. RESULTS: The results demonstrated that anti-influenza IgG
      and IgM were greater in active as compared with moderately active or sedentary
      participants. PBMC proliferation was lowest in sedentary subjects. Perceived
      stress was a significant predictor of IL-2. Greater optimism and social activity
      were associated with greater IL-10. Daily multivitamin intake was significantly
      correlated with IL-2. CONCLUSIONS: These results suggest that lifestyle factors
      including exercise may influence immune response to influenza immunization. The
      practice of regular, vigorous exercise was associated with enhanced immune
      response following influenza vaccination in older adults.

PMID- 12196491
TI  - Effect of a complete nutritional supplement on antibody response to influenza
      vaccine in elderly people.
AB  - BACKGROUND: The impact of influenza infection on morbidity and mortality in the
      elderly population can be severe. Influenza vaccination is not very effective in
      this age group, which is potentially related to impaired nutritional status. We
      investigated the effect of a 7-month nutritional supplementation on antibody
      response to influenza vaccine in elderly people. METHODS: Nineteen subjects aged
      65 years and older with a body mass index of 25 kg/m(2) or less were studied.
      Subjects received a complete liquid nutrition supplement containing energy,
      vitamins, and minerals, including enhanced levels of antioxidants or noncaloric
      placebo drink for 7 months. Antibody titers to influenza strains A/Sydney/5/97
      (SY), A/Beijing/262/95 (BE), and B/Yamanashi/166/98 (YA) before and 28 days after
      vaccination were measured. Age, gender, weight, height, serum albumin, serum
      prealbumin, hemoglobin, and serum vitamin E at baseline were registered. RESULTS:
      Mean fold increase upon vaccination for SY was significantly larger in the
      supplement group (2.76 +/- 0.66) compared to the placebo group (1.91 +/- 0.66).
      These differences were not observed for YA (1.73 +/- 0.31 vs 1.19 +/- 0.18) and
      BE (4.40 +/- 2.63 vs 5.76 +/- 3.34). For all three strains, there was no
      significant difference between groups in protective antibody levels (HI titer >
      or =40) after vaccination. CONCLUSIONS: We conclude that provision of a complete
      liquid nutrition supplement including enhanced levels of antioxidants may have a
      beneficial effect on antibody response to influenza vaccination in the elderly
      population. Further confirmation of these findings and their clinical
      consequences should be the subject of a larger study.

PMID- 12196492
TI  - Focus on functional decline in hospitalized older adults.

PMID- 12196493
TI  - Predictors of functional decline in hospitalized elderly patients: a systematic
      review.
AB  - BACKGROUND: This article will systematically review the methodological
      characteristics and results of studies of variables and indices that predict
      functional decline in older hospitalized patients. METHODS: We restricted this
      review to original longitudinal studies of predictors of either physical
      functional decline or nursing home admission among patients aged 60 and older.
      Two reviewers independently abstracted information on methodological
      characteristics and substantive results. RESULTS: Thirty articles were
      identified, derived from 27 different studies, reporting on 33 substudies.
      Substantial variability was found with respect to study design, outcomes
      measured, period of follow-up, predictors investigated, and analytic methods.
      Multivariable predictive indices were significantly associated with adverse
      outcomes in the majority of studies that investigated them, as were the following
      variables: age, diagnosis, activities of daily living, cognitive impairment
      (including delirium), and residence. CONCLUSIONS: The methodological
      heterogeneity of the studies identified limits quantitative synthesis of the
      results. Predictive indices for hospitalized elders appear to have moderate short
      term predictive ability.

PMID- 12196494
TI  - Assessment of driving with the global positioning system and video technology in
      young, middle-aged, and older drivers.
AB  - BACKGROUND: Driving is a complex task that is difficult to fully characterize
      objectively or in a blinded fashion. The main objective of this study was to
      determine the usefulness of the global positioning system (GPS) and video
      technology for examining age-related differences in driving. In this study, GPS
      was used to determine the position, velocity, and acceleration of a vehicle,
      driven by subjects of different ages, while video footage was used to provide a
      detailed context of the drive. METHODS: Twenty-four subjects who were young (20
      to 29; n = 6), middle-aged (30 to 64; n = 8), and older (65 years of age and
      older; n = 10) drove their own vehicles on a 30-km route of various types of
      roads, with a GPS receiver and video camera recording. RESULTS: The combination
      of GPS and video data allowed for the determination of many age-related driving
      differences. The young subjects drove faster, had a shorter deceleration distance
      and time, as well as a shorter acceleration time. Young subjects also had a
      substantially higher number of infraction demerit points primarily due to
      speeding, not stopping fully at stop signs, and following too closely. Although
      the older subjects had a smaller number of demerit points assessed, they tended
      to make different types of errors than the young subjects, including not stopping
      at all at a stop sign and turning errors. CONCLUSIONS: GPS and video technology
      offer new opportunities for the assessment of age-related driving performance.

PMID- 12196495
TI  - Vitamin B(12) deficiency and incontinence: is there an association?
AB  - BACKGROUND: This study investigated the relationship between B(12) (cobalamin)
      levels and incontinence in older outpatients using secondary data analysis.
      METHODS: Between 1991 and 1999, there were 929 patients (258 men and 671 women)
      for whom urinary incontinence (UI), fecal incontinence (FI), and B(12) were
      prospectively recorded. Covariates included race, gender, age, medications, Mini
      Mental State Examination, modified illness rating, and instrumental activities of
      daily living (IADLs). RESULTS: Some form of incontinence (UI or FI or both) was
      found in 41% of subjects, isolated UI in 34%, double incontinence (DI) in 12%,
      and isolated FI in 4%. Having UI increased the risk of also having FI (p <.0001).
      Serum B(12) levels of 300 pg/ml or less were not predictive of isolated UI or
      isolated FI. However, in logistic regression, DI was predicted by B(12) (odds
      ratio [OR] = 2.113, p =.0094), IADLs (OR = 0.810, p <.0001), cathartics/laxative
      use (OR = 1.902, p =.126), and diuretic use (OR = 2.226, p =.006). Considering
      isolated UI in women, higher IADLs reduced risk of UI (OR = 0.956, p =.002),
      while diuretics (OR = 1.481, p =.041) and antihistamines (OR = 1.909, p =.046)
      both increased risk of UI. In men, only use of anticonvulsant medications (OR =
      4.529, p =.023) increased risk of isolated UI. Greater physical illness in both
      genders increased risk of isolated FI (OR = 1.204, p =.006). CONCLUSIONS: These
      findings suggest that serum B(12) at levels of 300 pg/ml or less are not
      associated with isolated UI or isolated FI but may play a role in DI. A possible
      association of low B(12) levels with DI is intriguing because of the implications
      for treatment and prevention. More immediately, medication side effects should be
      considered when evaluating this problem.

PMID- 12196496
TI  - Relationship between body mass index and local quality of mandibular bone
      structure in elderly individuals.
AB  - BACKGROUND: Human bones decrease in density and increase in porosity beginning at
      about the third decade of life. The objective of this study was to determine
      whether mandibular bone mineral density (BMD) and some linear radiomorphometric
      measurements on dental panoramic radiograph (DPR) are correlated with different
      categories of body mass index (BMI) in elderly individuals. METHODS: Cortical
      width at gonion (GI), at antegonion (AI), and below mental foramen (MI) and the
      appearance of the cortex of the lower border of the mandible distal to the mental
      foramina due to resorptive changes (mandibular cortical index [MCI]) were
      measured bilaterally on the mandible on 136 DPRs of elderly individuals. Using
      DPRs and copper stepwedge, mandibular BMD was investigated densitometrically. All
      BMD values were expressed in equivalents of the actual stepwedge thickness. The
      patients with BMIs from 20 to 25 kg/m(2) were classified as category 1 (the
      generally accepted range of normal BMI), and the patients with BMIs higher than
      25 were classified as category 2 (heavy individuals with a heavy skeleton and a
      large amount of fat in the body). RESULTS: The results revealed statistically
      significant differences in all measured indices between different BMI categories
      (p <.05 for MI; p <.001 for GI and AI). Statistically significant differences
      were also found in BMD values between different BMI categories (p <.05); the
      differences were more pronounced in women. The patients with MCI category 3 had
      significantly lower BMD values in comparison to MCI category 2 (p <.01).
      Intraobserver agreement in GI, AI, MI measurement, and MCI assessments was
      excellent. CONCLUSIONS: Heavy people have higher BMD and higher values in linear
      radiomorphometric measurements than lighter people.

PMID- 12196497
TI  - Cognitive decline among female estrogen users in nursing homes.
AB  - BACKGROUND: Clinical and epidemiological research has been done regarding the
      potential therapeutic benefit of estrogen in outpatients with and without
      dementia; however, the effects of estrogen therapy on cognition in elderly
      nursing home patients have not been previously examined. METHODS: This
      retrospective cohort study compared 191 women estrogen users with 663 women
      nonestrogen users, matched according to age, nursing home facility, year of
      assessment, and baseline level of cognitive function. The outcome was decline in
      cognition, measured by the Cognitive Performance Scale, over a minimum follow-up
      period of 6 months. RESULTS: No significant difference was found in the rate of
      cognitive decline among estrogen users and nonusers. CONCLUSIONS: Estrogen
      therapy administered to nursing home residents is not associated with a reduction
      in cognitive decline. This study lends further support to recent controlled
      clinical trials that found no benefit for estrogen treatment on cognition in
      outpatients with dementia.

PMID- 12196498
TI  - Exercise and lumbar spine bone mineral density in postmenopausal women: a meta
      analysis of individual patient data.
AB  - BACKGROUND: Low bone mineral density (BMD) at the lumbar spine is a major public
      health problem among postmenopausal women. We conducted a meta-analysis of
      individual patient data (IPD) to examine the effects of exercise on lumbar spine
      BMD in postmenopausal women. METHODS: IPD were requested from a previously
      developed database of summary means from randomized and nonrandomized trials
      dealing with the effects of exercise on BMD. Two-way analysis of variance tests
      with pairwise comparisons (p < or =.05) and 95% confidence intervals (CIs) were
      used to determine the statistical significance for changes in lumbar spine BMD.
      RESULTS: Across 13 trials that included 699 subjects (355 exercise, 344 control),
      a statistically significant interaction was found between test and group (F =
      15.232, p =.000). Pairwise comparisons (Bonferroni t tests) revealed a
      statistically significant increase in final minus initial BMD for the exercise
      group ( +/- SD = 0.005 +/- 0.043 g/cm(2), t = 2.46, p =.014, 95% CI = 0.001
      0.009) and a statistically significant decrease in final minus initial BMD for
      the control group ( +/- SD = -0.007 +/- 0.045 g/cm(2), t = -3.051, p =.002, 95%
      CI = -0.012--0.002). Changes were equivalent to an approximate 2% benefit in
      lumbar spine BMD (exercise, +1%, control, -1%). CONCLUSIONS: The results of this
      IPD meta-analysis suggest that exercise helps to improve and maintain lumbar
      spine BMD in postmenopausal women.

PMID- 12196499
TI  - Cardiac autonomic nervous activities and cardiorespiratory fitness in older men.
AB  - BACKGROUND: Aging associated changes in sympatho-vagal activities have been
      widely studied. However, little is known about the association between
      cardiorespiratory fitness level and cardiac autonomic nervous activities in
      conjunction with baroreflex sensitivity in healthy older men. METHODS: We
      performed an incremental submaximal exercise test in 24 healthy, older men aged
      60-70 years. They were divided into physically fit (PF, oxygen uptake at
      anaerobic threshold [ATO(2)] = 25.2 +/- 0.85 ml.kg(-1).min(-1)) and physically
      unfit (PU, ATO(2) = 19.6 +/- 0.42 ml.kg(-1).min(-1)) groups, based upon the
      results of an incremental exercise stress test. The cardiac autonomic nervous
      system (ANS) activities were assessed by means of power spectral analysis of
      heart rate variability. Baroreflex sensitivity (BRS) testing was performed using
      simultaneous beat-by-beat blood pressure and heart rate measurement during a
      transition from supine horizontal position to 60 degrees head-up-tilting (HUT).
      RESULTS: At rest conditions, the high-frequency component ( p =.03) and total
      power ( p =.04) of heart rate variability spectrum were significantly higher in
      the PF group. The BRS assessed during passive HUT was also significantly higher
      (7.5 +/- 0.5 vs 3.0 +/- 0.4 ms.mm Hg(-1), p =.001) in the PF compared with the PU
      group. In addition, a significant correlation coefficient (r =.73, p =.001) was
      found between ATO(2) and BRS among the subjects. CONCLUSIONS: The maintenance of
      high cardiorespiratory function, i.e., higher ATO(2) through a life-long active
      lifestyle including endurance exercise, may play an important role in reserving
      cardiac ANS and BRS in older men.

PMID- 12196500
TI  - Genetic factors associated with the absence of atherosclerosis in octogenarians.
AB  - BACKGROUND: Atherosclerosis (ATS) is a common age-related disease of large
      arteries. The prevalence of older subjects with vascular successful aging (VaSA),
      defined as the absence of clinical symptoms and instrumental signs of ATS, is low
      in Western countries. The possible contribution of genetics to the VaSA
      phenomenon is not known. METHODS: We investigated the distribution of four
      genetic polymorphisms (angiotensin converting enzyme [ACE],
      methylenetetrahydrofolate reductase [MTHFR], apolipoprotein E [apo E], and
      paraoxonase [PON] genes) in 30 subjects with VaSA, 30 subjects with moderate
      carotid atherosclerosis (ATS group), and 161 controls with a negative history for
      cardiovascular disease. Clinical examination; ultrasonographic examination of
      carotid, vertebral, abdominal aortic, iliac, and femoral arteries; and
      electrocardiogram were performed. RESULTS: The frequency of PON 192 B allele was
      lower in VaSA patients (13%) compared with ATS patients (37%) and controls (46%)
      ( p =.06 and.006, respectively); B/B homozygotes were 27% in the ATS group, 12%
      in controls, and 0% in the VaSA group. The frequency of the MTHFR thermolable +
      allele was higher in VaSA (0.51) compared with ATS (0.39) and controls (0.40)
      (VaSA vs C, p =.006). No differences in the distribution of ACE I/D and apo E
      alleles emerged between the three groups. CONCLUSIONS: The low prevalence of the
      PON 192 B allele in the VaSA subjects suggests that this polymorphism might have
      an important role in VaSA, probably by hydrolyzing lipid peroxides and thus
      preventing low-density lipoprotein from undergoing the oxidative modification.
      This finding further supports the oxidative hypothesis of ATS.

PMID- 12196501
TI  - Relationship between dental occlusion and physical fitness in an elderly
      population.
AB  - BACKGROUND: The relationship between physical fitness and dental health status in
      elderly adults is still unknown. The purpose of the present study is to examine
      the relationship between physical fitness and occlusal condition of natural teeth
      in the elderly population. The sample consisted of 591 individuals aged 70 years
      and 158 aged 80 years selected from the registry of residents in Niigata city.
      METHODS: Hand grip strength (kg), leg extensor strength (kg), leg extensor power
      (watts), stepping rate (time per 10 seconds), and one-leg standing time with eyes
      open (seconds) were measured. The Eichner index was used as a measurement of
      occlusal condition. It was based on existing natural tooth contacts between
      maxilla and mandible in the bilateral premolar and molar regions and determined
      the three groups of classification used. In comparing physical fitness with
      Eichner index, multiple regression models were developed to adjust for variables
      such as age, gender, height, body weight, past medical history, blood pressure,
      serum albumin concentration, presence of lower back pain, smoking habit, marital
      status, and education. RESULTS: Multiple regression analyses revealed that leg
      extensor power (R(2) =.627, p <.05), stepping rate (R(2) =.159, p <.05), and one
      leg standing time with eyes open (R(2) =.179, p <.05) showed significant
      correlations with the Eichner index. CONCLUSIONS: Leg extensor power, stepping
      rate, and one-leg standing time with eyes open are useful indicators in
      evaluating lower extremity dynamic strength, agility, and balance function,
      respectively. These findings suggest that dental occlusal condition is associated
      with lower extremity dynamic strength, agility, and balance function in elderly
      adults.

PMID- 12196502
TI  - Response to "The Minnesota Senior Health Options Program: an early Effort at
      integrating care for the dually eligible".

PMID- 12196506
TI  - Reconstitution of nuclear protein export in isolated nuclear envelopes.
AB  - Signal-dependent nuclear protein export was studied in perforated nuclei and
      isolated nuclear envelopes of Xenopus oocytes by optical single transporter
      recording. Manually isolated and purified oocyte nuclei were attached to
      isoporous filters and made permeable for macromolecules by perforation. Export of
      a recombinant protein (GG-NES) containing the nuclear export signal (NES) of the
      protein kinase A inhibitor through nuclear envelope patches spanning filter pores
      could be induced by the addition of GTP alone. Export continued against a
      concentration gradient, and was NES dependent and inhibited by leptomycin B and
      GTPgammaS, a nonhydrolyzable GTP analogue. Addition of recombinant RanBP3, a
      potential cofactor of CRM1-dependent export, did not promote GG-NES export at
      stoichiometric concentration but gradually inhibited export at higher
      concentrations. In isolated filter-attached nuclear envelopes, export of GG-NES
      was virtually abolished in the presence of GTP alone. However, a preformed export
      complex consisting of GG-NES, recombinant human CRM1, and RanGTP was rapidly
      exported. Unexpectedly, export was strongly reduced when the export complex
      contained RanGTPgammaS or RanG19V/Q69L-GTP, a GTPase-deficient Ran mutant. This
      paper shows that nuclear transport, previously studied in intact and
      permeabilized cells only, can be quantitatively analyzed in perforated nuclei and
      isolated nuclear envelopes.

PMID- 12196507
TI  - Rapid microtubule-independent dynamics of Cdc20 at kinetochores and centrosomes
      in mammalian cells.
AB  - Cdc20 is a substrate adaptor and activator of the anaphase-promoting
      complex/cyclosome (APC/C), the E3 ubiquitin ligase whose activity is required for
      anaphase onset and exit from mitosis. A green fluorescent protein derivative,
      Cdc20-GFP, bound to centrosomes throughout the cell cycle and to kinetochores
      from late prophase to late telophase. We mapped distinct domains of Cdc20 that
      are required for association with kinetochores and centrosomes. FRAP measurements
      revealed extremely rapid dynamics at the kinetochores (t1/2 = 5.1 s) and spindle
      poles (t1/2 = 4.7 s). This rapid turnover is independent of microtubules. Rapid
      transit of Cdc20 through kinetochores may ensure that spindle checkpoint
      signaling at unattached/relaxed kinetochores can continuously inhibit APC/CCdc20
      targeting of anaphase inhibitors (securins) throughout the cell until all the
      chromosomes are properly attached to the mitotic spindle.

PMID- 12196508
TI  - The Saccharomyces cerevisiae Mob2p-Cbk1p kinase complex promotes polarized growth
      and acts with the mitotic exit network to facilitate daughter cell-specific
      localization of Ace2p transcription factor.
AB  - The Saccharomyces cerevisiae mitotic exit network (MEN) is a conserved signaling
      network that coordinates events associated with the M to G1 transition. We
      investigated the function of two S. cerevisiae proteins related to the MEN
      proteins Mob1p and Dbf2p kinase. Previous work indicates that cells lacking the
      Dbf2p-related protein Cbk1p fail to sustain polarized growth during early bud
      morphogenesis and mating projection formation (Bidlingmaier, S., E.L. Weiss, C.
      Seidel, D.G. Drubin, and M. Snyder. 2001. Mol. Cell. Biol. 21:2449-2462). Cbk1p
      is also required for Ace2p-dependent transcription of genes involved in
      mother/daughter separation after cytokinesis. Here we show that the Mob1p-related
      protein Mob2p physically associates with Cbk1p kinase throughout the cell cycle
      and is required for full Cbk1p kinase activity, which is periodically activated
      during polarized growth and mitosis. Both Mob2p and Cbk1p localize
      interdependently to the bud cortex during polarized growth and to the bud neck
      and daughter cell nucleus during late mitosis. We found that Ace2p is restricted
      to daughter cell nuclei via a novel mechanism requiring Mob2p, Cbk1p, and a
      functional nuclear export pathway. Furthermore, nuclear localization of Mob2p and
      Ace2p does not occur in mob1-77 or cdc14-1 mutants, which are defective in MEN
      signaling, even when cell cycle arrest is bypassed. Collectively, these data
      indicate that Mob2p-Cbk1p functions to (a) maintain polarized cell growth, (b)
      prevent the nuclear export of Ace2p from the daughter cell nucleus after mitotic
      exit, and (c) coordinate Ace2p-dependent transcription with MEN activation. These
      findings may implicate related proteins in linking the regulation of cell
      morphology and cell cycle transitions with cell fate determination and
      development.

PMID- 12196509
TI  - Proteomic analysis of the mammalian nuclear pore complex.
AB  - As the sole site of nucleocytoplasmic transport, the nuclear pore complex (NPC)
      has a vital cellular role. Nonetheless, much remains to be learned about many
      fundamental aspects of NPC function. To further understand the structure and
      function of the mammalian NPC, we have completed a proteomic analysis to identify
      and classify all of its protein components. We used mass spectrometry to identify
      all proteins present in a biochemically purified NPC fraction. Based on previous
      characterization, sequence homology, and subcellular localization, 29 of these
      proteins were classified as nucleoporins, and a further 18 were classified as NPC
      associated proteins. Among the 29 nucleoporins were six previously undiscovered
      nucleoporins and a novel family of WD repeat nucleoporins. One of these WD repeat
      nucleoporins is ALADIN, the gene mutated in triple-A (or Allgrove) syndrome. Our
      analysis defines the proteome of the mammalian NPC for the first time and paves
      the way for a more detailed characterization of NPC structure and function.

PMID- 12196510
TI  - Protein phosphatase 2A associates with and regulates atypical PKC and the
      epithelial tight junction complex.
AB  - Tight junctions (TJs) play a crucial role in the establishment of cell polarity
      and regulation of paracellular permeability in epithelia. Here, we show that upon
      calcium-induced junction biogenesis in Madin-Darby canine kidney cells, ABalphaC,
      a major protein phosphatase (PP)2A holoenzyme, is recruited to the apical
      membrane where it interacts with the TJ complex. Enhanced PP2A activity induces
      dephosphorylation of the TJ proteins, ZO-1, occludin, and claudin-1, and is
      associated with increased paracellular permeability. Expression of PP2A catalytic
      subunit severely prevents TJ assembly. Conversely, inhibition of PP2A by okadaic
      acid promotes the phosphorylation and recruitment of ZO-1, occludin, and claudin
      1 to the TJ during junctional biogenesis. PP2A negatively regulates TJ assembly
      without appreciably affecting the organization of F-actin and E-cadherin.
      Significantly, inhibition of atypical PKC (aPKC) blocks the calcium- and serum
      independent membrane redistribution of TJ proteins induced by okadaic acid.
      Indeed, PP2A associates with and critically regulates the activity and
      distribution of aPKC during TJ formation. Thus, we provide the first evidence for
      calcium-dependent targeting of PP2A in epithelial cells, we identify PP2A as the
      first serine/threonine phosphatase associated with the multiprotein TJ complex,
      and we unveil a novel role for PP2A in the regulation of epithelial aPKC and TJ
      assembly and function.

PMID- 12196511
TI  - Alteration of plant mitochondrial proton conductance by free fatty acids.
      Uncoupling protein involvement.
AB  - We characterized the uncoupling activity of the plant uncoupling protein from
      Solanum tuberosum (StUCP) using mitochondria from intact potato tubers or from
      yeast (Saccharomyces cerevisiae) expressing the StUCP gene. Compared with
      mitochondria from transfected yeast, StUCP is present at very low levels in
      intact potato mitochondrial membranes (at least thirty times lower) as shown by
      immunodetection with anti-UCP1 antibodies. Under conditions that ruled out
      undesirable effects of nucleotides and free fatty acids on uncoupling activity
      measurement in plant mitochondria, the linoleic acid-induced depolarization in
      potato mitochondria was insensitive to the nucleotides ATP, GTP, or GDP. In
      addition, sensitivity to linoleic acid was similar in potato and in control yeast
      mitochondria, suggesting that uncoupling occurring in potato mitochondria was
      because of a UCP-independent proton diffusion process. By contrast, yeast
      mitochondria expressing StUCP exhibited a higher sensitivity to free fatty acids
      than those from the control yeast and especially a marked proton conductance in
      the presence of low amounts of linoleic acid. However, this fatty acid-induced
      uncoupling was also insensitive to nucleotides. Altogether, these results suggest
      that uncoupling of oxidative phosphorylation and heat production cannot be the
      dominant feature of StUCP expressed in native potato tissues. However, it could
      play a role in preventing reactive oxygen species production as proposed for
      mammalian UCP2 and UCP3.

PMID- 12196512
TI  - The p53-activated gene, PAG608, requires a zinc finger domain for nuclear
      localization and oxidative stress-induced apoptosis.
AB  - The p53-activated gene PAG608, which encodes a nuclear zinc finger protein, is a
      p53-inducible gene that contributes to p53-mediated apoptosis. However, the
      mechanisms by which PAG608 is involved in the apoptosis of neuronal cells are
      still obscure. In this study, we demonstrated that expression of p53 was induced
      by 100 microm 6-hydroxydopamine (6-OHDA), accompanied by increased PAG608
      expression in PC12 cells. On the other hand, transient or permanent transfection
      of antisense PAG608 cDNA into PC12 cells significantly prevented apoptotic cell
      death induced by 100 microm 6-OHDA or 200 microm hydrogen peroxide but not by 250
      microm 1-methyl-4-phenylpyridinium ion. The 6-OHDA-induced activation of caspase
      3, DNA fragmentation, loss of mitochondrial membrane potential, and induction of
      p53 and Bax were also prevented in PC12 cells that stably expressed antisense
      PAG608 cDNA. These results suggest that PAG608 is associated with the apoptotic
      pathway induced by these oxidative stress-generating reagents, upstream of the
      collapse in the mitochondrial membrane potential in PC12 cells. Interestingly,
      transient transfection with PAG608 cDNA increased p53 expression in both PC12
      cells and B65 cells, indicating that PAG608 induced by p53 is able to induce p53
      expression in these cells inversely. Furthermore, transient transfection of a
      truncated mutant PAG608 cDNA, lacking the first zinc finger domain, inhibited 6
      OHDA-induced cell death and altered the nuclear and nucleolar localization of
      wild-type PAG608 in PC12 cells. These results suggest that PAG608 may induce or
      regulate p53 expression and translocate to the nucleus and nucleolus using its
      first zinc finger domain during oxidative stress-induced apoptosis of
      catecholamine-containing cells.

PMID- 12196513
TI  - High glucose stimulates synthesis of fibronectin via a novel protein kinase C,
      Rap1b, and B-Raf signaling pathway.
AB  - The molecular mechanism(s) by which high glucose induces fibronectin expression
      via G-protein activation in the kidney are largely unknown. This investigation
      describes the effect of high glucose (HG) on a small GTP-binding protein, Rap1b,
      expression and activation, and the relevance of protein kinase C (PKC) and Raf
      pathways in fibronectin synthesis in cultured renal glomerular mesangial cells
      (MCs). In vivo experiments revealed a dose-dependent increase in Rap1b expression
      in glomeruli of diabetic rat kidneys. Similarly, in vitro exposure of MCs to HG
      led to an up-regulation of Rap1b with concomitant increase in fibronectin (FN)
      mRNA and protein expression. The up-regulation of Rap1b mRNA was mitigated by the
      PKC inhibitors, calphostin C, and bisindolymaleimide, while also reducing HG-
      induced FN expression in non-transfected MCs. Overexpression of Rap1b by
      transfection with pcDNA 3.1/Rap1b in MCs resulted in the stimulation of FN
      synthesis; however, the PKC inhibitors had no significant effect in reducing FN
      expression in Rap1b-transfected MCs. Transfection of Rap1b mutants S17N (Ser -->
      Asn) or T61R (Thr --> Arg) in MCs inhibited the HG-induced increased FN
      synthesis. B-Raf and Raf-1 expression was investigated to assess whether Rap1b
      effects are mediated via the Raf pathway. B-Raf, and not Raf-1, expression was
      increased in MCs transfected with Rap1b. HG also caused activation of Rap1b,
      which was largely unaffected by anti-platelet-derived growth factor (PDGF)
      antibodies. HG-induced activation of Rap1b was specific, since Rap2b activation
      and expression of Rap2a and Rap2b were unaffected by HG. These findings indicate
      that hyperglycemia and HG cause an activation and up-regulation of Rap1b in renal
      glomeruli and in cultured MCs, which then stimulates FN synthesis. This effect
      appears to be PKC-dependent and PDGF-independent, but involves B-Raf, suggesting
      a novel PKC-Rap1b-B-Raf pathway responsible for HG-induced increased mesangial
      matrix synthesis, a hallmark of diabetic nephropathy.

PMID- 12196514
TI  - Human adipose tissue cells keep tight control on the angiotensin II levels in
      their vicinity.
AB  - Human adipose tissue expresses all components necessary for the local production
      of angiotensin II, which has multiple functions in adipose tissue, ranging from
      regulation of local blood flow to complex influences on tissue homeostasis. Still
      the mechanisms controlling human adipose tissue angiotensin II concentrations are
      not yet known. We investigated whether angiotensin II is degraded by human
      primary cultured preadipocytes and adipocytes and which enzymes are responsible
      for its metabolism. Distinct but transient angiotensin II production was limited
      by degradation due to consecutive proteolytic cleavage by endopeptidase and
      aminopeptidase activities. The endopeptidase could be identified as neprilysin
      expressed on the surface of both preadipocytes and adipocytes. Degradation of
      angiotensin II was preceded by a lag phase that was considerably longer in
      preadipocytes. This time span could not be explained by an induction of
      neprilysin nor by an increase in its surface localization. Following the lag
      phase, adipocytes showed a higher degradation activity than preadipocytes as
      mirrored by increased neprilysin levels and activity measured in their membrane
      fractions. Our findings demonstrate that human preadipocytes and adipocytes
      differentially express functional neprilysin and aminopeptidase activity involved
      in the regulation of angiotensin II concentrations in human adipose tissue.

PMID- 12196515
TI  - Active site mapping and substrate channeling in the sterol methyltransferase
      pathway.
AB  - Sterol methyltransferase (SMT) from Saccharomyces cerevisiae was purified from
      Escherichia coli BL21(DE3) and labeled with the mechanism-based irreversible
      inhibitor [3-3H]26,27-dehydrozymosterol (26,27-DHZ). A 5-kDa tryptic digest
      peptide fragment containing six acidic residues at positions Glu-64, Asp-65, Glu
      68, Asp-79, Glu-82, and Glu-98 was determined to contain the substrate analog
      covalently attached to Glu-68 by Edman sequencing and radioanalysis using C18
      reverse phase high performance liquid chromatography. Site-directed mutagenesis
      of the six acidic residues to leucine followed by activity assay of the purified
      mutants confirmed Glu-68 as the only residue to participate in affinity labeling.
      Equilibration studies indicated that zymosterol and 26,27-DHZ were bound to
      native and the E68L mutant with similar affinity, whereas S-adenosylmethionine
      was bound only to the native SMT, K(d) of about 2 microm. Analysis of the
      incubation products of the wild-type and six leucine mutants by GC-MS
      demonstrated that zymosterol was converted to fecosterol, 26,27-DHZ was converted
      to 26-homo-cholesta-8(9),23(24)E,26(26')-trienol as well as 26-homocholesta
      8(9),26(26')-3beta,24beta-dienol, and in the case of D79L and E82L mutants,
      zymosterol was also converted to a new product, 24-methylzymosta-8,25(27)-dienol.
      The structures of the methylenecyclopropane ring-opened olefins were determined
      unambiguously by a combination of (1)H and (13)C NMR techniques. A K(m) of 15
      microm, K(cat) of 8 x 10(-4) s(-1), and partition ratio of 0.03 was established
      for 26,27-DHZ, suggesting that the methylenecyclopropane can serve as a lead
      structure for a new class of antifungal agents. Taken together, partitioning that
      leads to loss of enzyme function is the result of 26,27-DHZ catalysis forming a
      highly reactive cationic intermediate that interacts with the enzyme in a region
      normally not occupied by the zymosterol high energy intermediate as a consequence
      of less than perfect control. Alternatively, the gain in enzyme function
      resulting from the production of a delta(25(27))-olefin originates with the
      leucine substitution directing substrate channeling along different reaction
      channels in a similar region at the active site.

PMID- 12196516
TI  - TRAIL receptor and CD95 signal to mitochondria via FADD, caspase-8/10, Bid, and
      Bax but differentially regulate events downstream from truncated Bid.
AB  - The death receptor ligand TRAIL arouses much interest for clinical application.
      We found that TRAIL receptor could induce cytochrome c (Cyt c) release from
      mitochondria in cells that failed to respond to CD95. Therefore, we examined
      whether these two closely related death receptors use different intermediates to
      convey the apoptotic signal to mitochondria. Dominant negative FADD, FLIP(L), or
      a Bid mutant lacking cleavage sites for caspase-8/10 completely inhibited Cyt c
      release in response to either receptor. Depletion of Bid from TRAIL- or CD95
      activated cytosols blocked their capacity to mediate Cyt c release from
      mitochondria in vitro, whereas Bax depletion reduced it. We conclude that FADD,
      caspase-8/10, and caspase-cleaved Bid are required for TRAIL receptor and CD95
      signaling to mitochondria, whereas Bax is a common accessory. In vitro, caspase-8
      treatment of cytosol from CD95-resistant cells permitted generation of truncated
      Bid and its association with mitochondria. However, this cytosol impaired the
      ability of truncated Bid to liberate Cyt c from exogenous mitochondria. We
      conclude that the TRAIL receptor can bypass or neutralize the activity of
      cytosolic factor that blocks truncated Bid function. This may benefit the
      capacity of TRAIL to break apoptosis resistance in tumor cells.

PMID- 12196517
TI  - Inhibitors of different structure induce distinguishing conformations in the
      omega loop, Cys69-Cys96, of mouse acetylcholinesterase.
AB  - We have shown previously that association of reversible active site ligands
      induces a conformational change in an omega loop (Omega loop), Cys(69)-Cys(96),
      of acetylcholinesterase. The fluorophore acrylodan, site-specifically
      incorporated at positions 76, 81, and 84, on the external portion of the loop not
      lining the active site gorge, shows changes in its fluorescence spectrum that
      reflect the fluorescent side chain moving from a hydrophobic environment to
      become more solvent-exposed. This appears to result from a movement of the Omega
      loop accompanying ligand binding. We show here that the loop is indeed flexible
      and responds to conformational changes induced by both active center and
      peripheral site inhibitors (gallamine and fasciculin). Moreover, phosphorylation
      and carbamoylation of the active center serine shows distinctive changes in
      acrylodan fluorescence spectra at the Omega loop sites, depending on the
      chirality and steric dimensions of the covalently conjugated ligand. Capping of
      the gorge with fasciculin, although it does not displace the bound ligand,
      dominates in inducing a conformational change in the loop. Hence, the ligand
      induced conformational changes are distinctive and suggest multiple loop
      conformations accompany conjugation at the active center serine. The fluorescence
      changes induced by the modified enzyme may prove useful in the detection of
      organophosphates or exposure to cholinesterase inhibitors.

PMID- 12196518
TI  - Calmodulin modulates the delay period between release of calcium from internal
      stores and activation of calcium influx via endogenous TRP1 channels.
AB  - In the present study we have explored the role of calmodulin (CaM) and inositol
      1,4,5-trisphosphate receptor (IP(3)R) in the communication process activated
      after the release of calcium from the endoplasmic reticulum (ER) and the
      activation of calcium influx via endogenous TRP1 channels from Chinese hamster
      ovary cells. Experiments using combined rapid confocal calcium and
      electrophysiology measurements uncovered a consistent delay of around 900 ms
      between the first detectable calcium released from the ER and the activation of
      the calcium current. This delay was evident with two different methods used to
      release calcium from the ER: either the blockade of the microsomal calcium ATPase
      with thapsigargin or activation of bradykinin receptors linked to the IP(3)
      cascade. Direct application of IP(3) or a peptide from the NH(2)-terminal region
      of the IP(3)R activated store operated calcium, reducing the delay period.
      Introduction of CaM into the cell via the patch pipette increased the delay
      period from 900 +/- 100 ms to 10 +/- 2.1 s (n = 18). Furthermore, the use of
      selective CaM antagonists W7 and trifluoperazine maleate resulted in a
      substantial reduction of the delay period to 200 +/- 100 ms with 5 microm
      trifluoperazine maleate (n = 16) and 150 +/- 50 ms with 500 nm W7 (n = 22). CaM
      reduced also the current density activated by thapsigargin or brandykinin to
      about 60% from control. The CaM antagonists did not affect significantly the
      current density. The results presented here are consistent with an antagonistic
      effect of IP(3)R and CaM for the activation of store operated calcium after
      depletion of the ER. The functional competition between the activating effect of
      IP(3)R and the inhibiting effect of CaM may modulate the delay period between the
      release of calcium from the ER and the activation of calcium influx observed in
      different cells, as well as the amount of current activated after depletion of
      the ER.

PMID- 12196519
TI  - Nutritional control of mRNA stability is mediated by a conserved AU-rich element
      that binds the cytoplasmic shuttling protein HuR.
AB  - The cationic amino acid transporter, Cat-1, is a high affinity transporter of the
      essential amino acids, arginine and lysine. Expression of the cat-1 gene
      increases during nutritional stress as part of the adaptive response to
      starvation. Amino acid limitation induces coordinate increases in stability and
      translation of the cat-1 mRNA, at a time when global protein synthesis decreases.
      It is shown here that increased cat-1 mRNA stability requires an 11 nucleotide AU
      rich element within the distal 217 bases of the 3'-untranslated region. When this
      217-nucleotide nutrient sensor AU-rich element (NS-ARE) is present in a chimeric
      mRNA it confers mRNA stabilization during amino acid starvation. HuR is a member
      of the ELAV family of RNA-binding proteins that has been implicated in regulating
      the stability of ARE-containing mRNAs. We show here that the cytoplasmic
      concentration of HuR increases during amino acid starvation, at a time when total
      cellular HuR levels decrease. In addition, RNA gel shift experiments in vitro
      demonstrated that HuR binds to the NS-ARE and binding was dependent on the 11
      residue AU-rich element. Moreover, HuR binding to the NS-ARE in extracts from
      amino acid-starved cells increased in parallel with the accumulation of
      cytoplasmic HuR. It is proposed that an adaptive response of cells to nutritional
      stress results in increased mRNA stability mediated by HuR binding to the NS-ARE.

PMID- 12196520
TI  - Protein kinase A site-specific phosphorylation regulates ATP-binding cassette A1
      (ABCA1)-mediated phospholipid efflux.
AB  - ATP-binding cassette A1 (ABCA1) is a key mediator of cholesterol and phospholipid
      efflux to apolipoprotein particles. We show that ABCA1 is a constitutively
      phosphorylated protein in both RAW macrophages and in a human embryonic kidney
      cell line expressing ABCA1. Furthermore, we demonstrate that phosphorylation of
      ABCA1 is mediated by protein kinase A (PKA) or a PKA-like kinase in vivo. Through
      site-directed mutagenesis studies of consensus PKA phosphorylation sites and in
      vitro PKA kinase assays, we show that Ser-1042 and Ser-2054, located in the
      nucleotide binding domains of ABCA1, are major phosphorylation sites for PKA.
      ApoA-I-dependent phospholipid efflux was decreased significantly by mutation of
      Ser-2054 alone and Ser-1042/Ser-2054 but was not significantly impaired with Ser
      1042 alone. The mechanism by which ABCA1 phosphorylation affected ApoA-I
      dependent phospholipid efflux did not involve either alterations in ApoA-I
      binding or changes in ABCA1 protein stability. These studies demonstrate a novel
      serine (Ser-2054) on the ABCA1 protein crucial for PKA phosphorylation and for
      regulation of ABCA1 transporter activity.

PMID- 12196521
TI  - Leucyl-tRNA synthetase consisting of two subunits from hyperthermophilic bacteria
      Aquifex aeolicus.
AB  - In a hyperthermophilic bacterium, Aquifex aeolicus, leucyl-tRNA synthetase
      (LeuRS) consists of two non-identical polypeptide subunits (alpha and beta),
      different from the canonical LeuRS, which has a single polypeptide chain. By PCR,
      using genome DNA of A. aeolicus as a template, genes encoding the alpha and beta
      subunits were amplified and cloned in Escherichia coli. The alpha subunit could
      not be expressed stably in vivo, whereas the beta subunit was overproduced and
      purified by a simple procedure. The beta subunit was inactive in catalysis but
      was able to bind tRNA(Leu). Interestingly, the heterodimer alphabeta-LeuRS could
      be overproduced in E. coli cells containing both genes and was purified to 95%
      homogeneity as a hybrid dimer. The kinetics of A. aeolicus LeuRS in pre-steady
      and steady states and cross-recognition of LeuRS and tRNA(Leu) from A. aeolicus
      and E. coli were studied. Magnesium concentration, pH value, and temperature
      aminoacylation optima were determined to be 12 mm, 7.8, and 70 degrees C,
      respectively. Under optimal conditions, A. aeolicus alphabeta-LeuRS is stable up
      to 65 degrees C.

PMID- 12196522
TI  - Regulation of Jak kinases by intracellular leptin receptor sequences.
AB  - Leptin signals the status of body energy stores via the leptin receptor (LR), a
      member of the Type I cytokine receptor family. Type I cytokine receptors mediate
      intracellular signaling via the activation of associated Jak family tyrosine
      kinases. Although their COOH-terminal sequences vary, alternatively spliced LR
      isoforms (LRa-LRd) share common NH(2)-terminal sequences, including the first 29
      intracellular amino acids. The so-called long form LR (LRb) activates Jak
      dependent signaling and is required for the physiologic actions of leptin. In
      this study, we have analyzed Jak activation by intracellular LR sequences under
      the control of the extracellular erythropoeitin (Epo) (Epo receptor/LRb
      chimeras). We show that Jak2 is the requisite Jak kinase for signaling by the LRb
      intracellular domain and confirm the requirement for the Box 1 motif for Jak2
      activation. A minimal LRb intracellular domain for Jak2 activation includes
      intracellular amino acids 31-48. Although the sequence requirements for
      intracellular amino acids 37-48 are flexible, intracellular amino acids 31-36 of
      LRb play a critical role in Jak2 activation and contain a loose homology motif
      found in other Jak2-activating cytokine receptors. The failure of short form
      sequences to function in Jak2 activation reflects the absence of this motif.

PMID- 12196523
TI  - Orientation of d-tubocurarine in the muscle nicotinic acetylcholine receptor
      binding site.
AB  - Ligand modification and receptor site-directed mutagenesis were used to examine
      binding of the competitive antagonist, d-tubocurarine (dTC), to the muscle-type
      nicotinic acetylcholine receptor (AChR). By using various dTC analogs, we
      measured the interactions of specific dTC functional groups with amino acid
      positions in the AChR gamma-subunit. Because data for mutations at residue
      gammaTyr(117) were the most consistent with direct interaction with dTC, we
      focused on that residue. Double mutant thermodynamic cycle analysis showed
      apparent interactions of gammaTyr(117) with both the 2-N and the 13'-positions of
      dTC. Examination of a dTC analog with a negative charge at the 13'-position
      failed to reveal electrostatic interaction with charged side-chain substitutions
      at gamma117, but the effects of side-chain substitutions remained consistent with
      proximity of Tyr(117) to the cationic 2-N of dTC. The apparent interaction of
      gammaTyr(117) with the 13'-position of dTC was likely mediated by allosteric
      changes in either dTC or the receptor. The data also show that cation-pi electron
      stabilization of the 2-N position is not required for high affinity binding.
      Molecular modeling of dTC within the binding pocket of the acetylcholine-binding
      protein places the 2-N in proximity to the residue homologous to gammaTyr(117).
      This model provides a plausible structural basis for binding of dTC within the
      acetylcholine-binding site of the AChR family that appears consistent with
      findings from photoaffinity labeling studies and with site-directed mutagenesis
      studies of the AChR.

PMID- 12196524
TI  - The X-ray crystallographic structure of Escherichia coli branching enzyme.
AB  - Branching enzyme catalyzes the formation of alpha-1,6 branch points in either
      glycogen or starch. We report the 2.3-A crystal structure of glycogen branching
      enzyme from Escherichia coli. The enzyme consists of three major domains, an
      NH(2)-terminal seven-stranded beta-sandwich domain, a COOH-terminal domain, and a
      central alpha/beta-barrel domain containing the enzyme active site. While the
      central domain is similar to that of all the other amylase family enzymes,
      branching enzyme shares the structure of all three domains only with isoamylase.
      Oligosaccharide binding was modeled for branching enzyme using the enzyme
      oligosaccharide complex structures of various alpha-amylases and cyclodextrin
      glucanotransferase and residues were implicated in oligosaccharide binding. While
      most of the oligosaccharides modeled well in the branching enzyme structure, an
      approximate 50 degrees rotation between two of the glucose units was required to
      avoid steric clashes with Trp(298) of branching enzyme. A similar rotation was
      observed in the mammalian alpha-amylase structure caused by an equivalent
      tryptophan residue in this structure. It appears that there are two binding modes
      for oligosaccharides in these structures depending on the identity and location
      of this aromatic residue.

PMID- 12196525
TI  - Lipoprotein(a) enhances advanced atherosclerosis and vascular calcification in
      WHHL transgenic rabbits expressing human apolipoprotein(a).
AB  - High lipoprotein(a) (Lp(a)) levels are a major risk factor for the development of
      atherosclerosis. The risk of elevated Lp(a) concentration is increased
      significantly in patients who also have high levels of low density lipoprotein
      (LDL) cholesterol. To test the hypothesis that increased plasma levels of Lp(a)
      may enhance the development of atherosclerosis in the setting of
      hypercholesterolemia, we generated Watanabe heritable hyperlipidemic (WHHL)
      transgenic (Tg) rabbits expressing human apolipoprotein(a) (apo(a)). We report
      here that Tg WHHL rabbits developed more extensive advanced atherosclerotic
      lesions than did non-Tg WHHL rabbits. In particular, the advanced atherosclerotic
      lesions in Tg WHHL rabbits were frequently associated with calcification, which
      was barely evident in non-Tg WHHL rabbits. To investigate the molecular mechanism
      of Lp(a)-induced vascular calcification, we examined the effect of human Lp(a) on
      cultured rabbit aortic smooth muscle cells and found that smooth muscle cells
      treated with Lp(a) showed increased alkaline phosphatase activity and enhanced
      calcium accumulation. These results demonstrate for the first time that Lp(a)
      accelerates advanced atherosclerotic lesion formation and may play an important
      role in vascular calcification.

PMID- 12196526
TI  - The p85 regulatory subunit controls sequential activation of phosphoinositide 3
      kinase by Tyr kinases and Ras.
AB  - Class IA phosphoinositide 3-kinase (PI3K) is a heterodimer composed of a p85
      regulatory and a p110 catalytic subunit that regulates a variety of cell
      responses, including cell division and survival. PI3K is activated following Tyr
      kinase stimulation and by Ras. We found that the C-terminal region of p85,
      including the C-Src homology 2 (C-SH2) domain and part of the inter-SH2 region,
      protects the p110 catalytic subunit from Ras-induced activation. Although the
      p110 activity associated with a C-terminal p85 deletion mutant increased
      significantly in the presence of an active form of Ras, purified wild type p85
      p110 was only slightly stimulated by active Ras. Nonetheless, incubation of
      purified p85-p110 with Tyr-phosphorylated peptides, which mimic the activated
      platelet-derived growth factor receptor, restored Ras-induced p85-p110
      activation. In conclusion, p85 inhibits p110 activation by Ras; this blockage is
      released by Tyr kinase stimulation, showing that the classical mechanism of class
      IA PI3K stimulation mediated by Tyr kinases also regulates Ras-induced PI3K
      activation.

PMID- 12196527
TI  - Regions of the mouse CD14 molecule required for toll-like receptor 2- and 4
      mediated activation of NF-kappa B.
AB  - Regions of mouse CD14 required for Toll-like receptor 2 (TLR2)- and TLR4-mediated
      activation of NF-kappaB were studied in transiently transfected 293 cells. Wild
      type CD14 enhanced lipopolysaccharide (LPS)-induced NF-kappaB-dependent reporter
      activity in cells expressing TLR4/MD-2, and deletion of amino acid regions 35-44,
      144-153, 235-243, and 270-275 impaired the TLR4-mediated activation. Unlike human
      CD14, mouse CD14 truncated at amino acid 151 lost the activity. Deletion of amino
      acids 35-44 or 235-243 also abrogated TLR2-mediated activation of NF-kappaB,
      whereas mutants lacking 144-153 and 270-275 retained the activity. Deletion and
      alanine substitution experiments revealed that amino acids 151-153 and 273-275
      were required for the TLR4-mediated activation. Both deletion mutants lacking
      amino acids 35-44 and 235-243 and alanine substitution mutants in regions 151-153
      and 273-275 were expressed on the cell surface and retained the ability to
      associate with TLR4. A cross-linking study with photoreactive LPS showed that the
      labeling intensities to CD14 mutants/TLR4/MD-2 were paralleled by the ability of
      CD14 mutants to increase TLR4-mediated activation. These results indicate that
      different regions of mouse CD14 are required for TLR4- and TLR2-mediated
      activation of NF-kappaB and suggest that amino acids 35-44, 151-153, 235-243, and
      273-275 of mouse CD14 play an important role in LPS binding and its transfer to
      TLR4/MD-2.

PMID- 12196528
TI  - Identification of ATF-2 as a transcriptional regulator for the tyrosine
      hydroxylase gene.
AB  - Transcriptional regulation of catecholamine-synthesizing genes is important for
      the determination of neurotransmitters during brain development. We found that
      three catecholamine-synthesizing genes were transcriptionally up-regulated in
      cloned PC12D cells overexpressing V-1, a protein that is highly expressed during
      postnatal brain development (1). To reveal the molecular mechanism to regulate
      the expression of tyrosine hydroxylase (TH), which is the rate-limiting enzyme
      for catecholamine biosynthesis, we analyzed the transcription factors responsible
      for TH induction in the V-1 clonal cells. First, by using reporter constructs, we
      found that the transcription mediated by cAMP-responsive element (CRE) was
      selectively enhanced in the V-1 cells, and TH promoter activity was totally
      dependent on the CRE in the promoter region of the TH gene. Next, immunoblot
      analyses and a transactivation assay using a GAL4 reporter system revealed that
      ATF-2, but not cAMP-responsive element-binding protein (CREB), was highly
      phosphorylated and activated in the V-1 cells, while both CREB and ATF-2 were
      bound to the TH-CRE. Finally, the enhanced TH promoter activity was competitively
      attenuated by expression of a plasmid containing the ATF-2 transactivation
      domain. These data demonstrated that activation of ATF-2 resulted in the
      increased transcription of the TH gene and suggest that ATF-2 may be deeply
      involved in the transcriptional regulation of catecholamine-synthesizing genes
      during neural development.

PMID- 12196530
TI  - Mechanism of insulin chain combination. Asymmetric roles of A-chain alpha-helices
      in disulfide pairing.
AB  - The A and B chains of insulin combine to form native disulfide bridges without
      detectable isomers. The fidelity of chain combination thus recapitulates the
      folding of proinsulin, a precursor protein in which the two chains are tethered
      by a disordered connecting peptide. We have recently shown that chain combination
      is blocked by seemingly conservative substitutions in the C-terminal alpha-helix
      of the A chain. Such analogs, once formed, nevertheless retain high biological
      activity. By contrast, we demonstrate here that chain combination is robust to
      non-conservative substitutions in the N-terminal alpha-helix. Introduction of
      multiple glycine substitutions into the N-terminal segment of the A chain
      (residues A1-A5) yields analogs that are less stable than native insulin and
      essentially without biological activity. (1)H NMR studies of a representative
      analog lacking invariant side chains Ile(A2) and Val(A3) (A chain sequence
      GGGEQCCTSICSLYQLENYCN; substitutions are italicized and cysteines are underlined)
      demonstrate local unfolding of the A1-A5 segment in an otherwise native-like
      structure. That this and related partial folds retain efficient disulfide pairing
      suggests that the native N-terminal alpha-helix does not participate in the
      transition state of the reaction. Implications for the hierarchical folding
      mechanisms of proinsulin and insulin-like growth factors are discussed.

PMID- 12196529
TI  - Pag, a putative tumor suppressor, interacts with the Myc Box II domain of c-Myc
      and selectively alters its biological function and target gene expression.
AB  - The highly conserved Myc Box II (MBII) domain of c-Myc is critically important
      for transformation and transcriptional regulation. A yeast two-hybrid screen
      identified Pag as a MBII-interacting protein. Pag, a member of the peroxiredoxin
      family, has been reported previously to bind to and inhibit the cytostatic
      properties of the c-Abl oncoprotein. We now show that Pag promotes increased cell
      size and confers a proapoptotic phenotype, two hallmark features of ectopic c-Myc
      overexpression. Pag and c-Myc also confer resistance to oxidative stress, a
      previously unrecognized property of the latter protein. In contrast, Pag inhibits
      tumorigenesis by c-Myc-overexpressing fibroblasts and causes a broad but
      selective loss of c-Myc target gene regulation. Pag is therefore an MBII
      interacting protein that can either mimic or enhance some of the c-Myc properties
      while at the same inhibiting others. These features, along with the previously
      identified interaction with c-Abl, provide support for the idea that Pag
      functions as a tumor suppressor.

PMID- 12196531
TI  - Allosteric enhancement of adaptational demethylation by a carboxyl-terminal
      sequence on chemoreceptors.
AB  - Sensory adaptation in bacterial chemotaxis is mediated by covalent modification
      of chemoreceptors. Specific glutamyl residues are methylated and demethylated in
      reactions catalyzed by methyltransferase CheR and methylesterase CheB. In
      Escherichia coli and Salmonella enterica serovar typhimurium, efficient
      adaptational modification by either enzyme is dependent on a conserved
      pentapeptide sequence at the chemoreceptor carboxyl terminus, a position distant
      from the sites of modification. For CheR-catalyzed methylation, previous work
      demonstrated that this sequence acts as a high affinity docking site, enhancing
      methylation by increasing enzyme concentration near methyl-accepting glutamates.
      We investigated pentapeptide-mediated enhancement of CheB-catalyzed demethylation
      and found it occurred by a distinctly different mechanism. Assays of binding
      between CheB and the pentapeptide sequence showed that it was too weak to have a
      significant effect on local enzyme concentration. Kinetic analyses revealed that
      interaction of the sequence and the methylesterase enhanced the rate constant of
      demethylation not the Michaelis constant. This allosteric activation occurred if
      the sequence was attached to chemoreceptor, but hardly at all if it was present
      as an isolated peptide. In addition, free peptide inhibited demethylation of the
      native receptor carrying the pentapeptide sequence at its carboxyl terminus.
      These observations imply that the allosteric change is transmitted through the
      protein substrate, not the enzyme.

PMID- 12196532
TI  - Vasopressin-dependent inhibition of the C-type natriuretic peptide receptor, NPR
      B/GC-B, requires elevated intracellular calcium concentrations.
AB  - Natriuretic peptides bind their cognate cell surface guanylyl cyclase receptors
      and elevate intracellular cGMP concentrations. In vascular smooth muscle cells,
      this results in the activation of the type I cGMP-dependent protein kinase and
      vasorelaxation. In contrast, pressor hormones like arginine-vasopressin,
      angiotensin II, and endothelin bind serpentine receptors that interact with G(q)
      and activate phospholipase Cbeta. The products of this enzyme, diacylglycerol and
      inositol trisphosphate, activate the conventional and novel forms of protein
      kinase C (PKC) and elevate intracellular calcium concentrations, respectively.
      The latter response results in vasoconstriction, which opposes the actions of
      natriuretic peptides. Previous reports have shown that pressor hormones inhibit
      natriuretic peptide receptors NPR-A or NPR-B in a variety of different cell
      types. Although the mechanism for this inhibition remains unknown, it has been
      universally accepted that PKC is an obligatory component of this pathway
      primarily because pharmacologic activators of PKC mimic the inhibitory effects of
      these hormones. Here, we show that in A10 vascular smooth muscle cells, neither
      chronic PKC down-regulation nor specific PKC inhibitors block the AVP-dependent
      desensitization of NPR-B even though both processes block PKC-dependent
      desensitization. In contrast, the cell-permeable calcium chelator, BAPTA-AM (1,2
      bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid, tetraacetoxymethyl ester),
      abrogates the AVP-dependent desensitization of NPR-B, and ionomycin, a calcium
      ionophore, mimics the AVP effect. These data show that the inositol
      trisphosphate/calcium arm of the phospholipase C pathway mediates the
      desensitization of a natriuretic peptide receptor in A10 cells. In addition, we
      report that CNP attenuates AVP-dependent elevations in intracellular calcium
      concentrations. Together, these data reveal a dominant role for intracellular
      calcium in the reciprocal regulation of these two important vasoactive signaling
      systems.

PMID- 12196533
TI  - The general anesthetic pentobarbital slows desensitization and deactivation of
      the glycine receptor in the rat spinal dorsal horn neurons.
AB  - Although many general anesthetics have been found to produce anesthetic and
      analgesic effects by augmenting GABA(A) receptor (GABA(A)R) function, the role of
      the glycine receptor (GlyR) in this process is not fully understood at the
      neuronal level in the spinal cord. We investigated the effects of a barbiturate
      general anesthetic, pentobarbital (PB), on the glycinergic miniature inhibitory
      postsynaptic currents (mIPSCs) and the responses to exogenously applied glycine,
      or taurine, a low affinity GlyR agonist, by using the whole-cell patch-clamp
      technique in the rat spinal dorsal horn neurons isolated using a novel mechanical
      method. Bath application of 30 microm PB significantly prolonged the decay time
      constant of the spontaneous glycinergic mIPSC without changing its amplitude and
      frequency. Co-application of 0.3 mm PB reduced the peak amplitude, affected the
      macroscopic desensitization and deactivation of the response to externally
      applied Gly in a concentration-dependent manner. In addition, the recovery of Gly
      response from desensitization was also prolonged by PB. However, PB did not
      change the desensitization and deactivation kinetics of the taurine-induced
      response. The GABA(A)R antagonist bicuculline (10 microm) did not affect the
      effect of PB on the Gly response. Thus, PB prolonged the spinal glycinergic
      mIPSCs by slowing desensitization and deactivation of GlyR. Two other
      structurally different intravenous anesthetics, i.e. propofol (10 microm) and
      etomidate (3 microm), prolonged the duration of the glycinergic mIPSC in the rat
      spinal dorsal horn neurons. In conclusion, on GlyR-Cl(-) channel complexes there
      may exist action site(s) of intravenous general anesthetics. GlyR and glycinergic
      neurotransmission may play an important role in the modulation of general
      anesthesia in the mammalian spinal cord.

PMID- 12196534
TI  - Crystal structure of Pseudomonas fluorescens mannitol 2-dehydrogenase binary and
      ternary complexes. Specificity and catalytic mechanism.
AB  - Long-chain mannitol dehydrogenases are secondary alcohol dehydrogenases that are
      of wide interest because of their involvement in metabolism and potential
      applications in agriculture, medicine, and industry. They differ from other
      alcohol and polyol dehydrogenases because they do not contain a conserved
      tyrosine and are not dependent on Zn(2+) or other metal cofactors. The structures
      of the long-chain mannitol 2-dehydrogenase (54 kDa) from Pseudomonas fluorescens
      in a binary complex with NAD(+) and ternary complex with NAD(+) and d-mannitol
      have been determined to resolutions of 1.7 and 1.8 A and R-factors of 0.171 and
      0.176, respectively. These results show an N-terminal domain that includes a
      typical Rossmann fold. The C-terminal domain is primarily alpha-helical and
      mediates mannitol binding. The electron lone pair of Lys-295 is steered by
      hydrogen-bonding interactions with the amide oxygen of Asn-300 and the main-chain
      carbonyl oxygen of Val-229 to act as the general base. Asn-191 and Asn-300 are
      involved in a web of hydrogen bonding, which precisely orients the mannitol O2
      proton for abstraction. These residues also aid in stabilizing a negative charge
      in the intermediate state and in preventing the formation of nonproductive
      complexes with the substrate. The catalytic lysine may be returned to its
      unprotonated state using a rectifying proton tunnel driven by Glu-292 oscillating
      among different environments. Despite low sequence homology, the closest
      structural neighbors are glycerol-3-phosphate dehydrogenase, N-(1-d
      carboxylethyl)-l-norvaline dehydrogenase, UDP-glucose dehydrogenase, and 6
      phosphogluconate dehydrogenase, indicating a possible evolutionary relationship
      among these enzymes.

PMID- 12196535
TI  - The La RNA-binding protein interacts with the vault RNA and is a vault-associated
      protein.
AB  - Vaults are highly conserved ubiquitous ribonucleoprotein particles with an
      undefined function. Three protein species (p240/TEP1, p193/VPARP, and p100/MVP)
      and a small RNA comprise the 13-MDa vault particle. The expression of the unique
      100-kDa major vault protein is sufficient to form the basic vault structure.
      Previously, we have shown that stable association of the vault RNA with the vault
      particle is dependent on its interaction with the p240/TEP1 protein. To identify
      other proteins that interact with the vault RNA, we used a UV-cross-linking
      assay. We find that a portion of the vault RNA is complexed with the La
      autoantigen in a separate smaller ribonucleoprotein particle. La interacts with
      the vault RNA (both in vivo and in vitro) presumably through binding to 3'
      uridylates. Moreover, we also demonstrate that the La autoantigen is the 50-kDa
      protein that we have previously reported as a protein that co-purifies with
      vaults.

PMID- 12196536
TI  - Weak strand displacement activity enables human DNA polymerase beta to expand
      CAG/CTG triplet repeats at strand breaks.
AB  - Using synthetic DNA constructs in vitro, we find that human DNA polymerase beta
      effectively catalyzes CAG/CTG triplet repeat expansions by slippage initiated at
      nicks or 1-base gaps within short (14 triplet) repeat tracts in DNA duplexes
      under physiological conditions. In the same constructs, Escherichia coli DNA
      polymerase I Klenow Fragment exo(-) is much less effective in expanding repeats,
      because its much stronger strand displacement activity inhibits slippage by
      enabling rapid extension through two downstream repeats into flanking non-repeat
      sequence. Polymerase beta expansions of CAG/CTG repeats, observed over a 32-min
      period at rates of approximately 1 triplet added per min, reveal significant
      effects of break type (nick versus gap), strand composition (CTG versus CAG), and
      dNTP substrate concentration, on repeat expansions at strand breaks. At
      physiological substrate concentrations (1-10 microm of each dNTP), polymerase
      beta expands triplet repeats with the help of weak strand displacement limited to
      the two downstream triplet repeats in our constructs. Such weak strand
      displacement activity in DNA repair at strand breaks may enable short tracts of
      repeats to be converted into longer, increasingly mutable ones associated with
      neurological diseases.

PMID- 12196537
TI  - Recognition of bacterial capsular polysaccharides and lipopolysaccharides by the
      macrophage mannose receptor.
AB  - The in vitro binding of the macrophage mannose receptor to a range of different
      bacterial polysaccharides was investigated. The receptor was shown to bind to
      purified capsular polysaccharides from Streptococcus pneumoniae and to the
      lipopolysaccharides, but not capsular polysaccharides, from Klebsiella
      pneumoniae. Binding was Ca(2+)-dependent and inhibitable with d-mannose. A fusion
      protein of the mannose receptor containing carbohydrate recognition domains 4-7
      and a full-length soluble form of the mannose receptor containing all domains
      external to the transmembrane region both displayed very similar binding
      specificities toward bacterial polysaccharides, suggesting that domains 4-7 are
      sufficient for recognition of these structures. Surprisingly, no direct
      correlation could be made between polysaccharide structure and binding to the
      mannose receptor, suggesting that polysaccharide conformation may play an
      important role in recognition. The full-length soluble form of the mannose
      receptor was able to bind simultaneously both polysaccharide via the carbohydrate
      recognition domains and sulfated oligosaccharide via the cysteine-rich domain.
      The possible involvement of the mannose receptor, either cell surface or soluble,
      in the innate and adaptive immune responses to bacterial polysaccharides is
      discussed.

PMID- 12196538
TI  - Association of a photoreceptor-specific tetraspanin protein, ROM-1, with triton X
      100-resistant membrane rafts from rod outer segment disk membranes.
AB  - This study reports the isolation and characterization of a Triton X-100-resistant
      membrane fraction from homogenates of rod outer segment (ROS) disk membranes
      purified free of the surrounding plasma membrane. A portion of the ROS disk
      membrane was found to be resistant to Triton X-100 extraction at 4 degrees C.
      This detergent-resistant fraction was isolated as a low buoyant density band on
      sucrose density gradients and exhibited an increase in light scattering detected
      at 600 nm. Biochemical analysis of the Triton X-100-resistant fraction showed it
      to be enriched in cholesterol and sphingomyelin relative to phospholipid and in
      phospholipid relative to protein compared with the soluble fraction. The Triton X
      100-resistant membranes described herein did not arise simply from partial
      solubilization of the ROS disk membranes because detergent-treated low buoyant
      density fractions isolated from homogenates with octyl glucopyranoside had
      cholesterol and sphingomyelin content indistinguishable from that of solubilized
      ROS disk homogenates. Analysis of proteins associated with the Triton X-100
      resistant fraction showed it to be enriched in the rim-specific protein ROM-1 and
      caveolin; surprisingly, the fusion protein peripherin/rds (where rds is retinal
      degeneration slow), also localized to the disk rim, was entirely absent from the
      membrane raft domain. The lipid profiles of the Triton X-100-resistant membranes
      were virtually identical in preparations homogenized in either the light or dark.
      Slightly more ROM-1 was recovered from samples prepared in the light (23%) than
      from samples prepared in the dark (13%), but peripherin/rds could not be detected
      in either preparation. When the Triton X-100-resistant membranes were treated
      with methyl-beta-cyclodextran to deplete membrane cholesterol, the resultant
      membranes contained slightly lower levels of ROM-1, specifically in the dimeric
      form. Cholesterol depletion also resulted in the collapse of the large caveolin
      complex to monomeric caveolae. The results presented herein characterize a pool
      of ROM-1, a photoreceptor tetraspanin protein, that may play a regulatory role in
      peripherin/rds-dependent fusion.

PMID- 12196539
TI  - The target of Drosophila photoreceptor synaptic transmission is a histamine-gated
      chloride channel encoded by ort (hclA).
AB  - By screening Drosophila mutants that are potentially defective in synaptic
      transmission between photoreceptors and their target laminar neurons, L1/L2,
      (lack of electroretinogram on/off transients), we identified ort as a candidate
      gene encoding a histamine receptor subunit on L1/L2. We provide evidence that the
      ort gene corresponds to CG7411 (referred to as hclA), identified in the
      Drosophila genome data base, by P-element-mediated germ line rescue of the ort
      phenotype using cloned hclA cDNA and by showing that several ort mutants exhibit
      alterations in hclA regulatory or coding sequences and/or allele-dependent
      reductions in hclA transcript levels. Other workers have shown that hclA, when
      expressed in Xenopus oocytes, forms histamine-sensitive chloride channels.
      However, the connection between these chloride channels and photoreceptor
      synaptic transmission was not established. We show unequivocally that hclA
      encoded channels are the channels required in photoreceptor synaptic transmission
      by 1) establishing the identity between hclA and ort and 2) showing that ort
      mutants are defective in photoreceptor synaptic transmission. Moreover, the
      present work shows that this function of the HCLA (ORT) protein is its native
      function in vivo.

PMID- 12196540
TI  - Structure of the epidermal growth factor receptor kinase domain alone and in
      complex with a 4-anilinoquinazoline inhibitor.
AB  - The crystal structure of the kinase domain from the epidermal growth factor
      receptor (EGFRK) including forty amino acids from the carboxyl-terminal tail has
      been determined to 2.6-A resolution, both with and without an EGFRK-specific
      inhibitor currently in Phase III clinical trials as an anti-cancer agent,
      erlotinib (OSI-774, CP-358,774, Tarceva(TM)). The EGFR family members are
      distinguished from all other known receptor tyrosine kinases in possessing
      constitutive kinase activity without a phosphorylation event within their kinase
      domains. Despite its lack of phosphorylation, we find that the EGFRK activation
      loop adopts a conformation similar to that of the phosphorylated active form of
      the kinase domain from the insulin receptor. Surprisingly, key residues of a
      putative dimerization motif lying between the EGFRK domain and carboxyl-terminal
      substrate docking sites are found in close contact with the kinase domain.
      Significant intermolecular contacts involving the carboxyl-terminal tail are
      discussed with respect to receptor oligomerization.

PMID- 12196541
TI  - Cell-free and cellular activities of a DNA sequence selective hairpin polyamide
      CBI conjugate.
AB  - Alkylating agents are generally highly reactive with DNA but demonstrate limited
      DNA sequence selectivity. In contrast, synthetic pyrrole-imidazole polyamides
      recognize specific DNA sequences with high affinity but are unable to permanently
      damage DNA. An eight-ring hairpin polyamide conjugated to the alkylating moiety
      cyclopropylpyrroloindole, related to the natural product CC-1065, affords a
      conjugate 1-CBI (polyamide 1-CBI (1-(chloromethyl)-5-hydroxyl-1,2-dihydro-3H
      benz[e]indole) conjugate), which binds to specific sequences in the minor groove
      of DNA and alkylates a single adenine flanking the polyamide binding site. In
      this study, we show that 1-CBI alkylates DNA in both plasmid and intracellular
      minichromosomal form and inhibits DNA replication under both cell-free and
      cellular conditions. In addition, it inhibits cell growth and arrests cells in
      the G2/M phase of the cell cycle.

PMID- 12196542
TI  - PDZ7 of glutamate receptor interacting protein binds to its target via a novel
      hydrophobic surface area.
AB  - Glutamate receptor interacting protein 1 (GRIP1) is a scaffold protein composed
      of seven PDZ (Postsynaptic synaptic density-95/Discs large/Zona occludens-1)
      domains. The protein plays important roles in the synaptic targeting of alpha
      amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors. The
      interaction between GRIP1 PDZ7 and a Ras guanine nucleotide exchange factor,
      GRASP-1, regulates synaptic distribution of AMPA receptors. Here, we describe the
      three-dimensional structure of GRIP1 PDZ7 determined by NMR spectroscopy. GRIP1
      PDZ7 contains a closed carboxyl group-binding pocket and a narrow alphaB/betaB
      groove that is not likely to bind to classical PDZ ligands. Unexpectedly, GRIP1
      PDZ7 contains a large solvent-exposed hydrophobic surface at a site distinct from
      the conventional ligand-binding alphaB/betaB-groove. NMR titration experiments
      show that GRIP1 PDZ7 binds to GRASP-1 via this hydrophobic surface. Our data
      uncover a novel PDZ domain-mediated protein interaction mode that may be
      responsible for multimerization of other PDZ domain-containing scaffold proteins.

PMID- 12196543
TI  - Depolarization induces intersubunit cross-linking in a S4 cysteine mutant of the
      Shaker potassium channel.
AB  - Voltage-gated potassium (K(v)) channels are integral membrane proteins, composed
      of four subunits, each comprising six (S1-S6) transmembrane segments. S1-S4
      comprise the voltage-sensing domain, and S5-S6 with the linker P-loop forms the
      ion conducting pore domain. During activation, S4 undergoes structural
      rearrangements that lead to the opening of the channel pore and ion conduction.
      To obtain details of these structural changes we have used the engineered
      disulfide bridge approach. For this we have introduced the L361C mutation at the
      extracellular end of S4 of the Shaker K channel and expressed the mutant channel
      in Xenopus oocytes. When exposed to mild oxidizing conditions (ambient oxygen or
      copper phenanthroline), Cys-361 formed an intersubunit disulfide bridge as
      revealed by the appearance of a dimeric band on Western blotting. As a
      consequence, the mutant channel suffered a significant loss in conductance
      (measured by two-electrode voltage clamp). Removal of native cysteines failed to
      prevent the disulfide formation, indicating that Cys-361 forms a disulfide with
      its counterpart in the neighboring subunit. The effect was voltage-dependent and
      occurred during channel activation after Cys-361 has been exposed to the
      extracellular phase. Although the disulfide bridge reduced the maximal
      conductance, it caused a hyperpolarizing shift in the conductance-voltage
      relationship and reduced the deactivation kinetics of the channel. The latter two
      effects suggest stabilization of the open state of the channel. In conclusion, we
      report that during activation the intersubunit distance between the N-terminal
      ends of the S4 segments of the L361C mutant Shaker K channel is reduced.

PMID- 12196544
TI  - Endogenously expressed Trp1 is involved in store-mediated Ca2+ entry by
      conformational coupling in human platelets.
AB  - Physical interaction between transient receptor potential (Trp) channels and
      inositol 1,4,5-trisphosphate receptors (IP(3)Rs) has been presented as a
      candidate mechanism for the activation of store-mediated Ca(2+) entry. The role
      of a human homologue of Drosophila transient receptor potential channel, hTrp1,
      in the conduction of store-mediated Ca(2+) entry was examined in human platelets.
      Incubation of platelets with a specific antibody, which recognizes the
      extracellular amino acid sequence 557-571 of hTrp1, inhibited both store
      depletion-induced Ca(2+) and Mn(2+) entry in a concentration-dependent manner.
      Stimulation of platelets with the physiological agonist thrombin activated
      coupling between the IP(3) receptor type II and endogenously expressed hTrp1.
      This event was reversed by refilling of the internal Ca(2+) stores but maintained
      after removal of the agonist if the stores were not allowed to refill. Inhibition
      of IP(3) recycling using Li(+) or inhibition of IP(3)Rs with xestospongin C or
      treatment with jasplakinolide, to stabilize the cortical actin filament network,
      abolished thrombin-induced coupling between hTrp1 and IP(3)R type II. Incubation
      with the anti-hTrp1 antibody inhibited thrombin-evoked Ca(2+) entry without
      affecting Ca(2+) release from intracellular stores. These results provide
      evidence for the involvement of hTrp1 in the activation of store-mediated Ca(2+)
      entry by coupling to IP(3)R type II in normal human cells.

PMID- 12196545
TI  - Roles of phosphorylation and helix propensity in the binding of the KIX domain of
      CREB-binding protein by constitutive (c-Myb) and inducible (CREB) activators.
AB  - cAMP-response element-binding protein (CREB)-binding protein (CBP) is a general
      transcriptional co-activator that mediates interactions between transcription
      factors and the basal transcription machinery. To obtain insights into the
      mechanism by which the KIX domain of CBP can recognize the transactivation
      domains of many different transcription factors, we have used NMR and biochemical
      analyses to study the interactions of KIX with the transactivation domain from
      the constitutive activator c-Myb and with the kinase-inducible transactivation
      domain (KID) from CREB. NMR chemical shift mapping shows that both activation
      domains bind to the same surface of KIX. In the unbound state, both the
      phosphorylated KID and c-Myb activation domains are only partly structured, and
      binding to KIX is coupled with folding to form an amphipathic helix. Helix
      destabilizing mutations significantly impair binding, whereas mutations that
      increase the intrinsic secondary structure content of the free phosphorylated KID
      peptide have only a small influence on binding affinity. Low affinity but
      specific binding of unphosphorylated KID to KIX was measured by ITC and was also
      observed in Western blot assays and by a fluorescence resonance energy transfer
      experiment in living cells. The large increase in the affinity for phosphorylated
      KID is due to favorable intermolecular interactions involving the phosphate
      moiety. After induction by phosphorylation, CREB is able to compete effectively
      with other transcriptional activators for binding to CBP.

PMID- 12196546
TI  - Crystal structure of the 47-kDa lipoprotein of Treponema pallidum reveals a novel
      penicillin-binding protein.
AB  - Syphilis is a complex sexually transmitted disease caused by the spirochetal
      bacterium Treponema pallidum. T. pallidum has remained exquisitely sensitive to
      penicillin, but the mode of action and lethal targets for beta-lactams are still
      unknown. We previously identified the T. pallidum 47-kDa lipoprotein (Tp47) as a
      penicillin-binding protein (PBP). Tp47 contains three hypothetical consensus
      motifs (SVTK, TEN, and KTG) that typically form the active center of other PBPs.
      Yet, in this study, mutations of key amino acids within these motifs failed to
      abolish the penicillin binding activity of Tp47. The crystal structure of Tp47 at
      a resolution of 1.95 A revealed a fold different from any other known PBP; Tp47
      is predominantly beta-sheet, in contrast to the alpha/beta-fold common to other
      PBPs. It comprises four distinct domains: two complex beta-sheet-containing N
      terminal domains and two C-terminal domains that adopt immunoglobulin-like folds.
      The three hypothetical PBP signature motifs do not come together to form a
      typical PBP active site. Furthermore, Tp47 is unusual in that it displays beta
      lactamase activity (k(cat) for penicillin = 271 +/- 6 s(-1)), a feature that
      hindered attempts to identify the active site in Tp47 by co-crystallization and
      mass spectrometric techniques. Taken together, Tp47 does not fit the classical
      structural and mechanistic paradigms for PBPs, and thus Tp47 appears to represent
      a new class of PBP.

PMID- 12196547
TI  - The poly(A) signal, without the assistance of any downstream element, directs RNA
      polymerase II to pause in vivo and then to release stochastically from the
      template.
AB  - Genes encoding polyadenylated mRNAs depend on their poly(A) signals for
      termination of transcription. Typically, transcription downstream of the poly(A)
      signal gradually declines to zero, but often there is a transient increase in
      polymerase density immediately preceding the decline. Special elements called
      pause sites are traditionally invoked to account for this increase. Using run-on
      transcription from the nuclei of transfected cells, we show that both the pause
      and the gradual decline that follow a poly(A) site are generated entirely by the
      poly(A) signal itself in a series of model constructs. We found no other elements
      to be involved and argue that the elements called pause sites do not function
      through pausing. Both the poly(A)-dependent pause and the subsequent decline
      occurred earlier for a stronger poly(A) signal than for a weaker one. Because the
      gradual decline resembles the abortive elongation that occurs downstream of many
      promoters, one model has proposed that the poly(A) signal flips the polymerase
      from the elongation mode to the abortive mode like a binary switch. We compared
      abortive elongators with poly(A) terminators and found a 4-fold difference in
      processivity. We conclude that poly(A) terminating polymerases do not merely
      revert to their prior state of low processivity but rather convert to a new
      termination-prone condition.

PMID- 12196548
TI  - A naturally occurring mutation in the SLC21A6 gene causing impaired membrane
      localization of the hepatocyte uptake transporter.
AB  - The organic anion transporter SLC21A6 (also known as OATP2, OATP-C, or LST-1) is
      involved in the hepatocellular uptake of a variety of endogenous and xenobiotic
      substances and drugs. We analyzed 81 human liver samples by immunoblotting and
      found one with a strongly reduced amount of SLC21A6 protein suggesting mutations
      in the SLC21A6 gene. The SLC21A6 cDNA from this sample contained five base pair
      changes in one allele; three of the mutations resulted in amino acid
      substitutions designated SLC21A6-N130D, SLC21A6-P155T, and SLC21A6-L193R. The
      former two were polymorphisms (SLC21A6*1b and SLC21A6*4), whereas SLC21A6-L193R
      represents the first naturally occurring mutation identified in one allele of the
      SLC21A6 gene, which affects protein maturation and organic anion transport. We
      introduced each of the mutations into the SLC21A6 cDNA and established stably
      transfected MDCKII cells expressing the respective mutant SLC21A6 protein.
      Immunofluorescence microscopy and uptake measurements were used to study
      localization and transport properties of the mutated proteins. Both proteins
      carrying the polymorphisms were sorted to the lateral membrane like wild-type
      SLC21A6, but their transport properties for the substrates cholyltaurine and
      17beta-glucuronosyl estradiol were altered. Importantly, most of the mutant
      protein SLC21A6-L193R was retained intracellularly, and this single amino acid
      exchange abolished transport function.

PMID- 12196549
TI  - Tumor necrosis factor alpha up-regulates non-lymphoid Fas-ligand following
      superantigen-induced peripheral lymphocyte activation.
AB  - Members of the tumor necrosis factor (TNF) and TNF receptor families play
      important roles in inducing apoptosis and mediating the inflammatory response.
      Activated T lymphocytes can trigger the expression of Fas-ligand on non-lymphoid
      tissue, such as intestinal epithelial cells (IEC), and this, in turn, can induce
      apoptosis in the T cells. Here, we examine the role of TNFalpha in this feedback
      regulation. Injection of TNFalpha into mice caused a rapid up-regulation of Fas
      ligand mRNA in IEC. TNFalpha-induced activation of the Fas-ligand promoter in IEC
      requires NF-kappaB as this was blocked by an I-kappaBalphaM super-repressor and
      by mutation of an NF-kappaB site in the Fas-ligand promoter. Activation of T
      cells by antigen induced Fas-ligand expression in IEC in vivo in wild type, but
      not in TNFalpha-/- or TNFR1-/- mice. These results define a novel pathway wherein
      TNFalpha, produced by activated T cells in the intestine, induce Fas-ligand
      expression in IEC. This is the first observation that one member of the TNF
      superfamily mediates the regulation of another family member and represents a
      potential feedback mechanism controlling lymphocyte infiltration and inflammation
      in the small intestine.

PMID- 12196550
TI  - Erythroid expression of the human alpha-spectrin gene promoter is mediated by
      GATA-1- and NF-E2-binding proteins.
AB  - alpha-Spectrin is a highly expressed membrane protein critical for the
      flexibility and stability of the erythrocyte. Qualitative and quantitative
      defects of alpha-spectrin are present in the erythrocytes of many patients with
      abnormalities of red blood cell shape including hereditary spherocytosis and
      elliptocytosis. We wished to determine the regulatory elements that determine the
      erythroid-specific expression of the alpha-spectrin gene. We mapped the 5' end of
      the alpha-spectrin erythroid cDNA and cloned the 5' flanking genomic DNA
      containing the putative alpha-spectrin gene promoter. Using transfection of
      promoter/reporter plasmids in human tissue culture cell lines, in vitro DNase I
      footprinting analyses, and gel mobility shift assays, an alpha-spectrin gene
      erythroid promoter with binding sites for GATA-1- and NF-E2-related proteins was
      identified. Both binding sites were required for full promoter activity. In
      transgenic mice, a reporter gene directed by the alpha-spectrin promoter was
      expressed in yolk sac, fetal liver, and erythroid cells of bone marrow but not
      adult reticulocytes. No expression of the reporter gene was detected in
      nonerythroid tissues. We conclude that this alpha-spectrin gene promoter contains
      the sequences necessary for low level expression in erythroid progenitor cells.

PMID- 12196551
TI  - Crystal structure of an in vitro affinity- and specificity-matured anti
      testosterone Fab in complex with testosterone. Improved affinity results from
      small structural changes within the variable domains.
AB  - A highly selective, high affinity recombinant anti-testosterone Fab fragment has
      been generated by stepwise optimization of the complementarity-determining
      regions (CDRs) by random mutagenesis and phage display selection of a monoclonal
      antibody (3-C(4)F(5)). The best mutant (77 Fab) was obtained by evaluating the
      additivity effects of different independently selected CDR mutations. The 77 Fab
      contains 20 mutations and has about 40-fold increased affinity (K(d) = 3 x 10(
      10) m) when compared with the wild-type (3-C(4)F(5)) Fab. To obtain structural
      insight into factors, which are needed to improve binding properties, we have
      determined the crystal structures of the mutant 77 Fab fragment with (2.15 A) and
      without testosterone (2.10 A) and compared these with previously determined wild
      type structures. The overall testosterone binding of the 77 Fab is similar to
      that of the wild-type. The improved affinity and specificity of the 77 Fab
      fragment are due to more comprehensive packing of the testosterone with the
      protein, which is the result of small structural changes within the variable
      domains. Only one important binding site residue Glu-95 of the heavy chain CDR3
      is mutated to alanine in the 77 Fab fragment. This mutation, originally selected
      from the phage library based on improved specificity, provides more free space
      for the testosterone D-ring. The light chain CDR1 of 77 Fab containing eight
      mutations has the most significant effect on the improved affinity, although it
      has no direct contact with the testosterone. The mutations of CDR-L1 cause a
      rearrangement in its conformation, leading to an overall fine reshaping of the
      binding site.

PMID- 12196552
TI  - Opsin-G11-mediated signaling pathway for photic entrainment of the chicken pineal
      circadian clock.
AB  - Light is a major environmental signal for entrainment of the circadian clock, but
      little is known about the intracellular phototransduction pathway triggered by
      light activation of the photoreceptive molecule(s) responsible for the phase
      shift of the clock in vertebrates. The chicken pineal gland and retina contain
      the autonomous circadian oscillators together with the photic entrainment
      pathway, and hence they represent useful experimental models for the clock
      system. Here we show the expression of G11alpha, an alpha subunit of
      heterotrimeric G-protein, in both tissues by cDNA cloning, Northern blot, and
      Western blot analyses. G11alpha immunoreactivity was colocalized with pinopsin in
      the chicken pineal cells and also with rhodopsin in the outer segments of retinal
      photoreceptor cells, suggesting functional coupling of G11alpha with opsins in
      the clock-containing photosensitive tissues. The physical interaction was
      examined by coimmunoprecipitation experiments, the results of which provided
      evidence for light- and GTP-dependent coupling between rhodopsin and G11alpha. To
      examine whether activation of endogenous G11 leads to a phase shift of the
      oscillator, Gq/11-coupled m1-type muscarinic acetylcholine receptor (mAChR) was
      ectopically expressed in the cultured pineal cells. Subsequent treatment of the
      cells with carbamylcholine (CCh), an agonist of mAChR, induced phase-dependent
      phase shifts of the melatonin rhythm in a manner very similar to the effect of
      light. In contrast, CCh treatment induced no measurable effect on the rhythm of
      nontransfected (control) cells or cells expressing G(i/o)-coupled m2-type mAChR,
      indicating selectivity of the G-protein activation. Together, our results
      demonstrate the existence of a G11-mediated opsin-signaling pathway contributing
      to the photic entrainment of the circadian clock.

PMID- 12196553
TI  - Differential resynchronisation of circadian clock gene expression within the
      suprachiasmatic nuclei of mice subjected to experimental jet lag.
AB  - Disruption of the circadian timing system arising from travel between time zones
      ("jet lag") and rotational shift work impairs mental and physical performance and
      severely compromises long-term health. Circadian disruption is more severe during
      adaptation to advances in local time, because the circadian clock takes much
      longer to phase advance than delay. The recent identification of mammalian
      circadian clock genes now makes it possible to examine time zone adjustments from
      the perspective of molecular events within the suprachiasmatic nucleus (SCN), the
      principal circadian oscillator. Current models of the clockwork posit interlocked
      transcriptional/post-translational feedback loops based on the light-sensitive
      Period (Per) genes and the Cryptochrome (Cry) genes, which are indirectly
      regulated by light. We show that circadian cycles of mPer expression in the mouse
      SCN react rapidly to an advance in the lighting schedule, whereas rhythmic mCry1
      expression advances more slowly, in parallel to the gradual resetting of the
      activity-rest cycle. In contrast, during a delay in local time the mPer and mCry
      cycles react rapidly, completing the 6 hr shift together by the second cycle, in
      parallel with the activity-rest cycle. These results reveal the potential for
      dissociation of mPer and mCry expression within the central oscillator during
      circadian resetting and a differential molecular response of the clock during
      advance and delay resetting. They highlight the indirect photic regulation of
      mCry1 as a potentially rate-limiting factor in behavioral adjustment to time zone
      transitions.

PMID- 12196554
TI  - Reversible translocation and activity-dependent localization of the calcium
      myristoyl switch protein VILIP-1 to different membrane compartments in living
      hippocampal neurons.
AB  - Visinin-like protein-1 (VILIP-1) belongs to the family of neuronal calcium sensor
      (NCS) proteins, a neuronal subfamily of EF-hand [corrected] calcium-binding
      proteins that are myristoylated at their N termini. NCS proteins are discussed to
      play roles in calcium-dependent signal transduction of physiological and
      pathological processes in the CNS. The calcium-dependent membrane association,
      the so-called calcium-myristoyl switch, localizes NCS proteins to a distinct
      cellular signaling compartment and thus may be a critical mechanism for the
      coordinated regulation of signaling cascades. To study whether the biochemically
      defined calcium-myristoyl switch of NCS proteins can occur in living neuronal
      cells, the reversible and stimulus-dependent translocation of green fluorescent
      protein (GFP)-tagged VILIP-1 to subcellular targets was examined by fluorescence
      microscopy in transfected cell lines and hippocampal primary neurons. In
      transiently transfected NG108-15 and COS-7 cells, a translocation of diffusely
      distributed VILIP-1-GFP but not of myristoylation-deficient VILIP-1-GFP to the
      plasma membrane and to intracellular targets, such as Golgi membranes, occurred
      after raising the intracellular calcium concentration with a calcium ionophore.
      The observed calcium-dependent localization was completely reversed after
      depletion of intracellular calcium by EGTA. Interestingly, a fast and reversible
      translocation of VILIP-1-GFP and translocation of endogenous VILIP-1 to
      specialized membrane structures was also observed after a depolarizing stimulus
      or activation of glutamate receptors in hippocampal neurons. These results show
      for the first time the reversibility and stimulus-dependent occurrence of the
      calcium-myristoyl switch in living neurons, suggesting a physiological role as a
      signaling mechanism of NCS proteins, enabling them to activate specific targets
      localized in distinct membrane compartments.

PMID- 12196555
TI  - Regulation of APP-dependent transcription complexes by Mint/X11s: differential
      functions of Mint isoforms.
AB  - Mints/X11s are neuron-specific (Mints 1 and 2) and ubiquitous (Mint 3) adaptor
      proteins composed of isoform-specific N-terminal sequences and common C-terminal
      phosphotyrosine-binding (PTB) and PDZ domains. We now show that all three Mints
      bind to the cytoplasmic tail of amyloid-beta precursor protein (APP) and
      presenilins and strongly increase the levels of cellular APP in transfected
      cells. Immunocytochemistry revealed that in neurons, Mints 1 and 2 were
      colocalized with APP in the trans-Golgi network, with lower levels throughout the
      cell body and neurites. Using an APP-dependent transactivation assay that uses a
      fusion protein of APP coupled to the potent transcription factor Gal4/VP16, we
      examined the effects of Mints on the proteolytic processing and putative
      transcriptional function of APP. Although all Mints were biochemically similar,
      only Mints 1 and 2 but not Mint 3 strongly inhibited transactivation by APP
      Gal4/VP16. Inhibition was enhanced by a mutation of the first PDZ domain and by
      deletion of the PDZ domains or the N-terminal sequences but abolished by
      inactivation of the PTB- and PDZ domains. Mint 1 also inhibited transactivation
      by the "precleaved" cytoplasmic tail of APP fused to Gal4/VP16, whereas Fe65
      (which binds to APP as strongly as Mints) enhanced transactivation. Our data
      suggest that Mints 1 and 2 but not Mint 3 have a specific effect on APP function
      that cannot be explained simply by their interaction with presenilins and occurs
      at least partly after cleavage of APP. In view of their biochemical similarity,
      the functional differences among Mints are unexpected, suggesting that Mints 1
      and 2 have a brain-specific function related to APP that is not executed by the
      ubiquitous Mint 3.

PMID- 12196556
TI  - No ligand binding in the GB2 subunit of the GABA(B) receptor is required for
      activation and allosteric interaction between the subunits.
AB  - The GABA(B) receptor plays important roles in the tuning of many synapses.
      Although pharmacological differences have been observed between various GABA(B)
      mediated effects, a single GABA(B) receptor composed of two subunits (GB1 and
      GB2) has been identified. Although GB1 binds GABA, GB2 plays a critical role in G
      protein activation. Moreover, GB2 is required for the high agonist affinity of
      GB1. Like any other family 3 G-protein-coupled receptors, GB1 and GB2 are
      composed of a Venus Flytrap module (VFTM) that usually contains the agonist
      binding site and a heptahelical domain. So far, there has been no direct
      demonstration that GB2 binds GABA or another endogenous ligand. Here, we have
      further refined the GABA-binding site of GB1 and characterized the putative
      binding site in the VFTM of GB2. None of the residues important for GABA binding
      in GB1 appeared to be conserved in GB2. Moreover, mutation of 10 different
      residues, alone or in combination, within the possible binding pocket of GB2
      affects neither GABA activation of the receptor nor the ability of GB2 to
      increase agonist affinity on GB1. These data indicate that ligand binding in the
      GB2 VFTM is not required for activation. Finally, although in either GB1 or the
      related metabotropic glutamate receptors most residues of the binding pocket are
      conserved from Caenorhabditis elegans to human, no such conservation is observed
      in GB2. This suggests that the GB2 VFTM does not constitute a binding site for a
      natural ligand.

PMID- 12196557
TI  - The postsynaptic glutamate receptor subunit DGluR-IIA mediates long-term
      plasticity in Drosophila.
AB  - The developing neuromuscular junctions (NMJs) of Drosophila larvae can undergo
      long-term strengthening of signal transmission, a process that has been shown
      recently to involve local subsynaptic protein synthesis and that is associated
      with an elevated synaptic accumulation of the postsynaptic glutamate receptor
      subunit DGluR-IIA. To analyze the role of altered postsynaptic glutamate receptor
      expression during this form of genetically induced junctional plasticity, we
      manipulated the expression levels of two so far-described postsynaptic receptor
      subunit genes, dglur-IIA and dglur-IIB, in wild-type animals and plasticity
      mutants. Here we show that elevated synaptic expression of DGluR-IIA, which was
      achieved by direct transgenic overexpression, by genetically increased
      subsynaptic protein synthesis, or by a reduced dglur-IIB gene copy number,
      results in an increased recruitment of active zones, a corresponding enhancement
      in the strength of junctional signal transmission, and a correlated addition of
      boutons to the NMJ. Ultrastructural evidence demonstrates that active zones
      appear throughout NMJs at a typical density regardless of genotype, suggesting
      that the space requirements of active zones are responsible for the homogeneous
      synapse distribution and that this regulation results in the observed growth of
      additional boutons at strengthened NMJs. These phenotypes were suppressed by
      reduced or eliminated DGluR-IIA expression, which resulted from either a reduced
      dglur-IIA gene copy number or transgenic overexpression of DGluR-IIB. Our results
      demonstrate that persistent alterations of neuronal activity and subsynaptic
      translation result in an elevated synaptic accumulation of DGluR-IIA, which
      mediates the observed functional strengthening and morphological growth
      apparently through the recruitment of additional active zones.

PMID- 12196558
TI  - Selective electrical silencing of mammalian neurons in vitro by the use of
      invertebrate ligand-gated chloride channels.
AB  - Selectively reducing the excitability of specific neurons will (1) allow for the
      creation of animal models of human neurological disorders and (2) provide insight
      into the global function of specific sets of neurons. We focus on a combined
      genetic and pharmacological approach to silence neurons electrically. We express
      invertebrate ivermectin (IVM)-sensitive chloride channels (Caenorhabditis elegans
      GluCl alpha and beta) with a Sindbis virus and then activate these channels with
      IVM to produce inhibition via a Cl- conductance. We constructed a three-cistron
      Sindbis virus that expresses the alpha and beta subunits of a glutamate-gated
      chloride channel (GluCl) along with the green fluorescent protein (EGFP) marker.
      Expression of the C. elegans channel does not affect the normal spike activity or
      GABA/glutamate postsynaptic currents of cultured embryonic day 18 hippocampal
      neurons. At concentrations as low as 5 nm, IVM activates a Cl- current large
      enough to silence infected neurons effectively. This conductance reverses in 8
      hr. These low concentrations of IVM do not potentiate GABA responses. Comparable
      results are observed with plasmid transfection of yellow fluorescent protein
      tagged (EYFP) GluCl alpha and cyan fluorescent protein-tagged (ECFP) GluCl beta.
      The present study provides an in vitro model mimicking conditions that can be
      obtained in transgenic mice and in viral-mediated gene therapy. These experiments
      demonstrate the feasibility of using invertebrate ligand-activated Cl- channels
      as an approach to modulate excitability.

PMID- 12196559
TI  - Lack of neurodegeneration in transgenic mice overexpressing mutant amyloid
      precursor protein is associated with increased levels of transthyretin and the
      activation of cell survival pathways.
AB  - Tg2576 mice overexpress a mutant form of human amyloid precursor protein with the
      Swedish mutation (APP(Sw)), resulting in high beta-amyloid (Abeta) levels in the
      brain. Despite this, amyloid plaques do not develop until 12 months of age, and
      there is no neuronal loss in mice as old as 16 months. Gene expression profiles
      in the hippocampus and cerebellum of 6-month-old APP(Sw) mice were compared with
      age-matched controls. The expression of transthyretin, a protein shown to
      sequester Abeta and prevent amyloid fibril formation in vitro, and several genes
      in the insulin-signaling pathway, e.g., insulin-like growth factor-2, were
      increased selectively in the hippocampus of APP(Sw) mice. Concomitant activation
      of the insulin-like growth factor-1 receptor, Akt, and extracellular signal
      regulated protein kinase 1 and 2 as well as increased phosphorylation of Bad also
      were unique to the hippocampus of APP(Sw) mice. In addition, the increased
      expression of transthyretin and insulin-like growth factor-2 and the increased
      phosphorylation of Bad in hippocampal neurons were maintained in 12-month-old
      APP(Sw) mice when compared with age-matched controls. These results suggest that
      the slow progression and lack of full-fledged Alzheimer's disease pathology in
      the hippocampal neurons of APP(Sw) mice result from the genetic reprogramming of
      neural cells to cope with increased levels of Abeta.

PMID- 12196560
TI  - 5-HT3 receptors mediate serotonergic fast synaptic excitation of neocortical
      vasoactive intestinal peptide/cholecystokinin interneurons.
AB  - Neocortical neurons expressing the serotonin 5-HT3 receptor (5-HT3R) were
      characterized in rat acute slices by using patch-clamp recordings combined with
      single-cell RT-PCR and histochemical labeling. The 5-HT3A receptor subunit was
      expressed selectively in a subset of GABAergic interneurons coexpressing
      cholecystokinin (CCK) and vasoactive intestinal peptide (VIP). The 5-HT3B subunit
      was never detected, indicating that 5-HT3Rs expressed by neocortical interneurons
      did not contain this subunit. In 5-HT3A-expressing VIP/CCK interneurons,
      serotonin induced fast membrane potential depolarizations by activating an inward
      current that was blocked by the selective 5-HT3R antagonist tropisetron.
      Furthermore, we observed close appositions between serotonergic fibers and the
      dendrites and somata of 5-HT3R-expressing neurons, suggestive of possible
      synaptic contacts. Indeed, in interneurons exhibiting rapid excitation by
      serotonin, local electrical stimulations evoked fast EPSCs of large amplitude
      that were blocked by tropisetron. Finally, 5-HT3R-expressing neurons were also
      excited by a nicotinic agonist, indicating that serotonergic and cholinergic fast
      synaptic transmission could converge onto VIP/CCK interneurons. Our results
      establish a clear correlation between the presence of the 5-HT3A receptor subunit
      in neocortical VIP/CCK GABAergic interneurons, its functional expression, and its
      synaptic activation by serotonergic afferent fibers from the brainstem raphe
      nuclei.

PMID- 12196561
TI  - Myelin proteolipid protein forms a complex with integrins and may participate in
      integrin receptor signaling in oligodendrocytes.
AB  - Myelination of axons in the CNS by oligodendrocytes is a process critical to
      rapid and efficient impulse conduction. A new role for the myelin proteolipid
      protein (PLP), the most abundant protein of CNS myelin, has been identified, in
      studies showing PLP interaction with signaling proteins in oligodendrocytes. In
      particular, these studies suggest that the PLP protein may be involved in
      signaling through integrins in oligodendrocytes. Stimulation of muscarinic
      acetylcholine receptors on oligodendrocytes induced formation of a tripartite
      complex containing PLP, calreticulin, and alpha(v)-integrin. PLP interacted
      directly with the cytoplasmic domain of the alpha(v)-integrin. Complex formation
      was mediated by phospholipase C and Ca2+ binding to the high affinity binding
      site on calreticulin. This complex appears important for binding of fibronectin
      to oligodendrocytes. These data establish a novel function for PLP as a part of
      the integrin signaling complex in oligodendrocytes and suggest that
      neurotransmitter-mediated integrin receptor signaling may be involved in
      myelinogenesis.

PMID- 12196562
TI  - In vitro neurotoxicity of methylisothiazolinone, a commonly used industrial and
      household biocide, proceeds via a zinc and extracellular signal-regulated kinase
      mitogen-activated protein kinase-dependent pathway.
AB  - Neurodegenerative disorders in humans may be triggered or exacerbated by exposure
      to occupational or environmental agents. Here, we show that a brief exposure to
      methylisothiazolinone, a widely used industrial and household biocide, is highly
      toxic to cultured neurons but not to glia. We also show that the toxic actions of
      this biocide are zinc dependent and require the activation of p44/42
      extracellular signal-regulated kinase (ERK) via a 12-lipoxygenase-mediated
      pathway. The cell death process also involves activation of NADPH oxidase,
      generation of reactive oxygen species, DNA damage, and overactivation of poly(ADP
      ribose) polymerase, all occurring downstream from ERK phosphorylation. The toxic
      effects of methylisothiazolinone and related biocides on neurons have not been
      reported previously. Because of their widespread use, the neurotoxic consequences
      of both acute and chronic human exposure to these toxins need to be evaluated.

PMID- 12196563
TI  - Structural evidence that propofol stabilizes different GABA(A) receptor states at
      potentiating and activating concentrations.
AB  - The GABA(A) receptor is a target of many general anesthetics, such as propofol.
      General anesthetic binding sites are distinct from the GABA binding sites. At low
      concentrations, the anesthetics potentiate the currents induced by submaximal
      GABA concentrations. At higher concentrations the anesthetics directly activate
      GABA(A) receptors. In contrast, benzodiazepines, such as diazepam, only
      potentiate currents induced by submaximal GABA concentrations. Channel kinetic
      studies suggest that these drugs stabilize different receptor states. We
      previously showed that the accessibility of the anionic sulfhydryl reagent p
      chloromercuribenzenesulfonate (pCMBS(-)) applied extracellularly to cysteines
      substituted for residues in the GABA(A) alpha1 subunit M3 membrane-spanning
      segment was state-dependent. The subset of pCMBS(-)-accessible, M3 segment
      cysteine mutants acts as a reporter for receptor conformation. Here we show that
      pCMBS(-), applied in the presence of a potentiating concentration of propofol,
      reacts with a subset of alpha1 subunit, M3 segment, cysteine-substitution mutants
      (Y294C, V297C, I302C, F304C). In the presence of a directly activating
      concentration of propofol pCMBS(-) reacts with a different subset of the M3
      cysteine-substitution mutants (Y294C, S299C, I302C, E303C, A305C). These subsets
      are distinct from the subsets of M3 cysteine-substitution mutants that are
      reactive with pCMBS(-) in the absence and presence of GABA and in the presence of
      diazepam. We hypothesize that distinct subsets of reactive residues represent
      distinct conformations or ensembles of conformations of the receptor. These
      results provide structural evidence for at least five distinct receptor states,
      three nonconducting states, resting, diazepam-bound and potentiating propofol
      bound, and two conducting-desensitized states, the activating propofol-bound and
      GABA-bound states.

PMID- 12196564
TI  - The presence and role of the tetrodotoxin-resistant sodium channel Na(v)1.9 (NaN)
      in nociceptive primary afferent neurons.
AB  - This is the first examination of sensory receptive properties and associated
      electrophysiological properties in vivo of dorsal root ganglion (DRG) neurons
      that express the TTX-resistant sodium channel Na(v)1.9 (NaN). Intracellular
      recordings in lumbar DRGs in Wistar rats enabled units with dorsal root C-,
      Adelta-, or Aalpha/beta-fibers to be classified as nociceptive, low-threshold
      mechanoreceptive (LTM), or unresponsive. Intracellular dye injection enabled
      subsequent immunocytochemistry for Na(v)1.9-like immunoreactivity (Na(v)1.9-LI).
      Na(v)1.9-LI was expressed selectively in nociceptive-type (C- and A-fiber
      nociceptive and C-unresponsive) units. Of the nociceptive units, 64, 54, and 31%
      of C-, Adelta-, and Aalpha/beta-fiber units, respectively, were positive for
      Na(v)1.9-LI. C-unresponsive units were included in the nociceptive-type group on
      the basis of their nociceptor-like membrane properties; 91% were positive.
      Na(v)1.9-LI was undetectable in Adelta- or Aalpha/beta-fiber LTM units and in one
      C-LTM unit. Na(v)1.9-LI intensity was correlated negatively with soma size and
      conduction velocity in nociceptive units and with conduction velocity in C-fiber
      units. There was a positive correlation with action potential rise time in
      nociceptive-type units with membrane potentials equal to or more negative than 
      50 mV. The data provide direct evidence that Na(v)1.9 is expressed selectively in
      (but not in all) C- and A-fiber nociceptive-type units and suggest that Na(v)1.9
      contributes to membrane properties that are typical of nociceptive neurons.

PMID- 12196565
TI  - AMPA receptors and kainate receptors encode different features of afferent
      activity.
AB  - Postsynaptic kainate receptors (KARs) have been found in the CNS along with AMPA
      receptors (AMPARs), but because KAR-mediated EPSCs are much smaller and slower
      than AMPAR-mediated EPSCs, it remains unclear whether these postsynaptic KARs are
      functionally significant. In this study we measured KAR- and AMPAR-mediated EPSPs
      in hippocampal interneurons, and then we used these EPSPs in a model to examine
      the effects of afferent firing on each receptor. In this model the KARs generated
      a large tonic depolarization when activated by a small population of afferent
      fibers firing asynchronously at physiologically relevant firing rates (1-5 Hz).
      At 3-5 Hz this tonic depolarization exceeded the peak depolarization mediated by
      AMPARs in response to the same afferent activity. We also found that, unlike
      AMPARs, KARs did not generate large oscillations in membrane potential during
      theta rhythms. When simulated EPSCs were injected into interneurons to mimic
      afferents firing at 5 Hz, we found that currents simulating KARs elicited more
      spiking than currents simulating AMPARs. We also found that simulated AMPARs, but
      not KARs, could transmit presynaptic theta rhythms into postsynaptic spiking at
      the theta rhythm. Our results suggest that synaptically activated KARs have a
      strong influence on membrane potential and that AMPARs and KARs differ in their
      ability to encode temporal information.

PMID- 12196566
TI  - Prostaglandin and protein kinase A-dependent modulation of vanilloid receptor
      function by metabotropic glutamate receptor 5: potential mechanism for thermal
      hyperalgesia.
AB  - In addition to its role as a CNS neurotransmitter, glutamate has been shown
      recently to be an important component of the peripheral inflammation response. We
      demonstrated previously that the group I metabotropic glutamate receptors
      (mGluRs) mGlu1 and mGlu5 are expressed in the peripheral terminals of sensory
      neurons and that activation of group I mGluRs in the skin increases thermal
      sensitivity. In the present study, we provide evidence suggesting that group I
      mGluRs increase thermal sensitivity by enhancing vanilloid (capsaicin) receptor
      function. We show that mGlu5 potentiates capsaicin responses in mouse sensory
      neurons by the phospholipase C pathway but not by activation of protein kinase C.
      Rather, the effects are mediated by the metabolism of diacylglycerol and the
      production of prostaglandins via the cyclooxygenase pathway, leading to
      activation of the cAMP-dependent protein kinase subsequent to prostanoid receptor
      activation. Behavioral thermal sensitization in mice induced by intraplantar
      injection of mGlu1/5 agonists was also blocked by inhibitors of protein kinase A
      and cyclooxygenase, suggesting that a similar signaling pathway operates in vivo.
      These results demonstrate a novel signaling pathway in sensory neurons and
      provide a plausible mechanism for the enhancement of thermal sensitivity that
      occurs with inflammation and after activation of mGluRs on peripheral sensory
      neuron terminals.

PMID- 12196567
TI  - Brain-derived neurotrophic factor triggers transcription-dependent, late phase
      long-term potentiation in vivo.
AB  - Acute intrahippocampal infusion of brain-derived neurotrophic factor (BDNF) leads
      to long-term potentiation (BDNF-LTP) of synaptic transmission at medial perforant
      path-->granule cell synapses in the rat dentate gyrus. Endogenous BDNF is
      implicated in the maintenance of high-frequency stimulation-induced LTP (HFS
      LTP). However, the relationship between exogenous BDNF-LTP and HFS-LTP is
      unclear. First, we found that BDNF-LTP, like HFS-LTP, is associated with
      enhancement in both synaptic strength and granule cell excitability (EPSP-spike
      coupling). Second, treatment with a competitive NMDA receptor (NMDAR) antagonist
      blocked HFS-LTP but had no effect on the development or magnitude of BDNF-LTP.
      Thus, NMDAR activation is not required for the induction or expression of BDNF
      LTP. Formation of stable, late phase HFS-LTP requires mRNA synthesis and is
      coupled to upregulation of the immediate early gene activity-regulated
      cytoskeleton-associated protein (Arc). Local infusion of the transcription
      inhibitor actinomycin D (ACD) 1 hr before or immediately before BDNF infusion
      inhibited BDNF-LTP and upregulation of Arc protein expression. ACD applied 2 hr
      after BDNF infusion had no effect, defining a critical time window of
      transcription-dependent synaptic strengthening. Finally, the functional role of
      BDNF-LTP was assessed in occlusion experiments with HFS-LTP. HFS-LTP was induced,
      and BDNF was infused at time points corresponding to early phase (1 hr) or late
      phase (4 hr) HFS-LTP. BDNF applied during the early phase led to normal BDNF-LTP.
      In contrast, BDNF-LTP was completely occluded during the late phase. The results
      strongly support a role for BDNF in triggering transcription-dependent, late
      phase LTP in the intact adult brain.

PMID- 12196568
TI  - The myotonia congenita mutation A331T confers a novel hyperpolarization-activated
      gate to the muscle chloride channel ClC-1.
AB  - Mutations in the muscle chloride channel gene CLCN1 cause myotonia congenita, an
      inherited disorder of skeletal muscle excitability leading to a delayed
      relaxation after muscle contraction. Here, we examine the functional consequences
      of a novel disease-causing mutation that predicts the substitution of alanine by
      threonine at position 331 (A331T) by whole-cell patch-clamp recording of
      recombinant mutant channels. A331T hClC-1 channels exhibit a novel slow gate that
      activates during membrane hyperpolarization and closes at positive potentials.
      This novel gate acts in series with fast opening and closing transitions that are
      common to wild-type (WT) and mutant channels. Under conditions at which this
      novel gate is not activated, i.e., a holding potential of 0 mV, the typical
      depolarization-induced activation gating of WT hClC-1 was only slightly affected
      by the mutation. In contrast, A331T hClC-1 channels with an open slow gate
      display an altered voltage dependence of open probability. These novel gating
      features of mutant channels produce a decreased open probability at -85 mV, the
      normal muscle resting potential, leading to a reduced resting chloride
      conductance of affected muscle fibers. The A331T mutation causes an unprecedented
      alteration of ClC-1 gating and reveals novel processes defining transitions
      between open and closed states in ClC chloride channels.

PMID- 12196569
TI  - Unhampered prion neuroinvasion despite impaired fast axonal transport in
      transgenic mice overexpressing four-repeat tau.
AB  - Transmissible spongiform encephalopathies often are caused by peripheral uptake
      of infectious prions, and the peripheral nervous system is involved in prion
      spread to the brain. Although the cellular prion protein is subjected to fast
      axonal transport, the mechanism of intranerval transport of infectious prions is
      unclear. Here we administered prions intranervally to transgenic mice
      overexpressing the four-repeat human tau protein, which exhibit defective fast
      axonal transport. These mice showed unaltered neuroinvasion, suggesting that
      transport mechanisms distinct from fast axonal transport effect prion
      neuroinvasion along peripheral nerves. Surprisingly, scrapie-sick tau transgenic
      mice accumulated intraneuronal deposits of hyperphosphorylated tau protein. The
      coincidence of tau and prion pathology resembled Gerstmann-Straussler-Scheinker
      syndrome. These findings identify tau pathology as a possible end stretch of
      prion-induced neurodegeneration.

PMID- 12196570
TI  - Endophilin is critically required for synapse formation and function in
      Drosophila melanogaster.
AB  - Studies in cell-free systems and the lamprey giant synapse have implicated
      crucial roles for amphiphysin and endophilin in synaptic transmission. However,
      null mutants at the amphiphysin locus of Drosophila are viable and have no
      demonstrable synaptic vesicle-recycling defect. This has necessitated a re
      examination of the role of Src homology 3 domain-containing proteins in synaptic
      vesicle recycling. In this report, we show that endophilin-deficient eye clones
      in Drosophila have an altered electroretinogram. A characteristic of this defect
      is its aggravation during heightened visual stimulation. It is shown that
      endophilin is primarily required in the nervous system. Decreased endophilin
      activity results in alterations in the neuromuscular junction structure and
      physiology. Immunofluorescence studies show colocalization of endophilin with
      dynamin consistent with a possible role in synaptic vesicle recycling.

PMID- 12196571
TI  - cGMP/protein kinase G-dependent inhibition of N-type Ca2+ channels induced by
      nitric oxide in human neuroblastoma IMR32 cells.
AB  - Although data from our laboratory and others suggest that nitric oxide (NO)
      exerts an overall inhibitory action on high-voltage-activated Ca2+ channels,
      conflicting observations have been reported regarding its effects on N-type
      channels. We performed whole-cell and cell-attached patch-clamp recordings in
      IMR32 cells to clarify the functional role of NO in the modulation of N channels
      of human neuronal cells. During depolarizing steps to +10 mV from V(h) = -90 mV,
      the NO donor, sodium nitroprusside (SNP; 200 microm), reduced macroscopic N
      currents by 34% (p < 0.01). The magnitude of inhibition was similar at all
      voltages tested (range, -40 to +50 mV). No significant inhibition was observed
      when SNP was applied together with the NO scavenger, 2-(4-carboxyphenyl)-4,4,5,5
      tetramethyl-imidazoline-1-oxyl-3-oxide potassium salt (300 microm), or after cell
      treatment with the guanylate cyclase inhibitor, 1H-[1,2,4] oxadiazole [4,3-a]
      quinoxalin-1-one (10 microm). 8-bromoguanosine-cGMP (8-Br-cGMP) (400 microm)
      mimicked the effects of SNP, reducing Ba2+ currents by 37% (p < 0.001). Cell
      treatment with the protein kinase G (PKG) inhibitor KT5823 (1 microm) or
      guanosine 3',5'-cyclic monophosphorothioate, 8-(4-chloro-phenylthio)-Rp-isomer,
      triethylammonium salt (20 microm) virtually abolished the effects of 8-Br-cGMP.
      At the single-channel level, 8-Br-cGMP reduced the channel open probability by
      59% and increased both the mean shut time and the null sweep probability, but it
      had no significant effects on channel conductance, mean open time, or latency of
      first openings. These data suggest that NO inhibits N-channel gating through cGMP
      and PKG. The consequent decrease in Ca2+ influx through these channels may affect
      different neuronal functions, including neurotransmitter release.

PMID- 12196572
TI  - Dynamic pattern of reg-2 expression in rat sensory neurons after peripheral nerve
      injury.
AB  - The 16 kDa pancreatitis-associated protein Reg-2 has recently been shown to
      facilitate the regeneration of motor and sensory neurons after peripheral nerve
      injury in the adult rat. Reg-2 has also been shown to be a neurotrophic factor
      that is an essential intermediate in the pathways through which CNTF supports the
      survival of motor neurons during development. Here we report the dynamic
      expression of Reg-2 in rat sensory neurons after peripheral nerve injury. Reg-2
      is normally not expressed by dorsal root ganglion (DRG) cells, but we show, using
      immunocytochemistry, that Reg-2 is rapidly upregulated in DRG cells after sciatic
      nerve transection and after 24 hr recovery is expressed almost exclusively in
      small-diameter neurons that bind the lectin Griffonia simplicifolia IB4 and
      express the purinoceptor P2X3. However, by 7 d after axotomy, Reg-2 is expressed
      in medium to large neurons and coexists partly with the neuropeptides galanin and
      neuropeptide Y, which are also upregulated after peripheral nerve transection. At
      this time point, Reg-2 is no longer expressed in small neurons, and there is no
      colocalization with IB4 binding neurons, demonstrating a shift in Reg-2
      expression from one subset of DRG neurons to another. We also show by double
      labeling for activating transcription factor 3, a transcription factor that is
      upregulated after nerve injury, that Reg-2 expression occurs predominantly in
      axotomized DRG cells but that a small percentage of uninjured DRG cells also
      upregulate Reg-2. The selective expression within IB4/P2X3 cells, and the dynamic
      shift from small to large cells, is unique among DRG peptides and suggests that
      Reg-2 has a distinctive role in the injury response.

PMID- 12196573
TI  - Immunohistochemical evidence of seizure-induced activation of trkB receptors in
      the mossy fiber pathway of adult mouse hippocampus.
AB  - Genetic and pharmacological perturbations suggest that tyrosine receptor kinase B
      (trkB) receptor activation promotes limbic epileptogenesis, but whether or where
      trkB activation occurs during epileptogenesis is uncertain. Because activation of
      trk receptors involves phosphorylation of specific tyrosine residues (Segal et
      al., 1996), the availability of antibodies that selectively recognize the
      phosphorylated form of trk receptors at the Shc site permits an
      immunohistochemical assessment of trk receptor activation. We reported previously
      increased phospho-specific trk (p-trk) immunoreactivity in the mossy fiber
      pathway of the hippocampus during epileptogenesis in rats (Binder et al., 1999b).
      Because the p-trk antibody does not distinguish among trkA, trkB, and trkC, the
      identity of the neurotrophin receptor(s) undergoing phosphorylation was
      uncertain. The development of mice carrying a point mutation of the Shc binding
      site (Y515F) in the trkB gene (trkB(shc)) provided an opportunity to test the
      hypothesis that trkB is the neurotrophin receptor undergoing phosphorylation.
      Epileptogenesis in wild-type (WT) mice was associated with increased p-trk
      immunoreactivity in both the mossy fiber pathway and CA3 stratum oriens of
      hippocampus. In contrast, the epileptogenesis-associated increase of p-trk
      immunoreactivity was reduced in trkB(shc) mutant mice. The development of
      epileptogenesis as measured by electrophysiological and behavioral indices did
      not differ between trkB(shc) mutant and WT mice. These data demonstrate that the
      neurotrophin receptor trkB undergoes phosphorylation in the mossy fiber pathway
      and CA3 stratum oriens of the hippocampus during limbic epileptogenesis. In
      addition, the signaling pathways activated by the Shc site of trkB exert no
      detectable regulatory effects on limbic epileptogenesis.

PMID- 12196574
TI  - Activation of presynaptic 5-hydroxytryptamine 2A receptors facilitates excitatory
      synaptic transmission via protein kinase C in the dorsolateral septal nucleus.
AB  - Effects of 5-hydroxytryptamine (5-HT) on EPSPs and EPSCs in the rat dorsolateral
      septal nucleus (DLSN) were examined in the presence of GABA(A) and GABA(B)
      receptor antagonists. Bath application of 5-HT (10 microm) for 5-10 min increased
      the amplitude of the EPSP and EPSC. (+/-)-8-hydroxy-2-(di-N-propylamino)tetralin
      hydrobromide (10 microm), an agonist for 5-HT1A and 5-HT7 receptors, did not
      facilitate the EPSP. alpha-Methyl-5-HT (10 microm), a 5-HT2 receptor agonist,
      increased the amplitude of the EPSC. Alpha-methyl-5-(2-thienylmethoxy)-1H-indole
      3-ethanamine (10 microm) and 6-chloro-2-(1-piperazinyl)pyrazine (10 microm),
      selective 5-HT2B and 5-HT2C receptor agonists, respectively, had no effect on the
      EPSP. The 5-HT-induced facilitation of the EPSP was blocked by ketanserin (10
      microm), a 5-HT2A/2C receptor antagonist. However, N-desmethylclozapine (10
      microm), a selective 5-HT2C receptor antagonist, did not block the facilitation
      of the EPSP induced by alpha-methyl-5-HT. The inward current evoked by exogenous
      glutamate was unaffected by 5-HT. 5-HT (10 microm) and alpha-methyl-5-HT (10
      microm) increased the frequency of miniature EPSPs (mEPSPs) without changing the
      mEPSP amplitude. The ratio of the paired pulse facilitation was significantly
      decreased by 5-HT and alpha-methyl-5-HT. The 5-HT-induced facilitation of the
      EPSP was blocked by calphostin C (100 nm), a specific protein kinase C (PKC)
      inhibitor, but not by N-[2-(p-bromocinnamylamino)ethyl]-5-isoquinolinesulfonamide
      (10 microm), a protein kinase A inhibitor. Phorbol 12,13-dibutyrate (3 microm)
      mimicked the facilitatory effects of 5-HT. These results suggest that 5-HT
      enhances the EPSP by increasing the release of glutamate via presynaptic 5-HT2A
      receptors that link with PKC in rat DLSN neurons.

PMID- 12196575
TI  - Plane of cell cleavage and numb distribution during cell division relative to
      cell differentiation in the developing retina.
AB  - Progenitor cells in the early developing nervous system can divide symmetrically,
      giving rise to two daughter cells that divide again, or asymmetrically, giving
      rise to one cell that differentiates and one that divides again. It has been
      suggested that the orientation of the cell cleavage plane during mitosis
      determines the type of division. A marker of early cell differentiation, the RA4
      antigen, was used to identify regions of the developing chick retina with and
      without differentiating cells, and the orientation of the cleavage plane was
      characterized for mitotic figures in each region. No difference was found in the
      frequency of any orientation between the regions with or without differentiating
      cells. Furthermore, in the region of the retina with differentiating cells, the
      RA4 antigen was present in mitotic figures with every possible orientation. Thus,
      the orientation of the cleavage plane appears to be unrelated to whether or not a
      division produces a cell that differentiates. It has also been suggested that the
      intracellular protein Numb mediates neurogenesis via asymmetric localization
      during cell division. Numb localization was compared with expression of markers
      of early cell differentiation, the RA4 antigen and Delta. Differentiating and
      nondifferentiating cells were found both with and without Numb expression. Cells
      with a cleavage plane parallel to the retinal surface were polarized, such that
      Numb and/or the RA4 antigen, when present, were only in the daughter cell
      farthest from the ventricle. These findings indicate a need to reconsider current
      hypotheses regarding the key features underlying symmetric and asymmetric
      divisions in the developing nervous system.

PMID- 12196577
TI  - Aggrecan glycoforms contribute to the molecular heterogeneity of perineuronal
      nets.
AB  - The perineuronal net forms the extracellular matrix of many neurons in the CNS,
      surrounding neuron cell bodies and proximal dendrites in a mesh-like structure
      with open "holes" at the sites of synaptic contacts. The perineuronal net is
      first detected late in development, approximately coincident with the
      transformation of the CNS from an environment conducive to neuronal growth and
      motility to one that is restrictive, suggesting a role for the perineuronal net
      in this developmental transition. Perineuronal nets show a great degree of
      molecular heterogeneity. Using monoclonal antibodies Cat-301, Cat-315, and Cat
      316, we have shown previously that although all antibodies recognize chondroitin
      sulfate proteoglycans of similar sizes, each antibody recognizes perineuronal
      nets on distinct but overlapping sets of neurons in the adult cat CNS. An
      understanding of the heterogeneity demonstrated by these antibodies is critical
      to understanding the organization and function of perineuronal nets. Using
      aggrecan knock-out mice (cmd), we have now determined that all three antibodies
      recognize aggrecan. Chemical and enzymatic deglycosylation show that the
      differences revealed by the three antibodies arise from differential
      glycosylation of aggrecan. We further demonstrate that aggrecan mRNA is expressed
      relatively late in development and that neurons themselves are likely the
      predominant cellular sites of aggrecan expression. This work indicates that
      neurons can directly regulate the composition of their extracellular matrix by
      regulated synthesis and differential glycosylation of aggrecan in a cell type
      specific manner. These results have important implications for the role of
      regulated microheterogeneity of glycosylation in the CNS.

PMID- 12196576
TI  - Matrix metalloproteinases limit functional recovery after spinal cord injury by
      modulation of early vascular events.
AB  - Inflammation in general and proteinases generated as a result are likely
      mediators of early secondary pathogenesis after spinal cord injury. We report
      that matrix metalloproteinase-9 (MMP-9) plays an important role in blood-spinal
      cord barrier dysfunction, inflammation, and locomotor recovery. MMP-9 was present
      in the meninges and neurons of the uninjured cord. MMP-9 increased rapidly after
      a moderate contusion spinal cord injury, reaching a maximum at 24 hr, becoming
      markedly reduced by 72 hr, and not detectable at 7 d after injury. It was seen in
      glia, macrophages, neutrophils, and vascular elements in the injured spinal cord
      at 24 hr after injury. The natural tissue inhibitors of MMPs were unchanged over
      this time course. MMP-9-null mice exhibited significantly less disruption of the
      blood-spinal cord barrier, attenuation of neutrophil infiltration, and
      significant locomotor recovery compared with wild-type mice. Similar findings
      were observed in mice treated with a hydroxamic acid MMP inhibitor from 3 hr to 3
      d after injury, compared with the vehicle controls. Moreover, the area of
      residual white matter at the lesion epicenter was significantly greater in the
      inhibitor-treated group. This study provides evidence that MMP-9 plays a key role
      in abnormal vascular permeability and inflammation within the first 3 d after
      spinal cord injury, and that blockade of MMPs during this critical period
      attenuates these vascular events and leads to improved locomotor recovery. Our
      findings suggest that early inhibition of MMPs may be an efficacious strategy for
      the spinal cord-injured patient.

PMID- 12196578
TI  - Doublecortin is required in mice for lamination of the hippocampus but not the
      neocortex.
AB  - Doublecortin (DCX) is a microtubule-associated protein that is required for
      normal neocortical and hippocampal development in humans. Mutations in the X
      linked human DCX gene cause gross neocortical disorganization (lissencephaly or
      "smooth brain") in hemizygous males, whereas heterozygous females show a mosaic
      phenotype with a normal cortex as well as a second band of misplaced
      (heterotopic) neurons beneath the cortex ("double cortex syndrome"). We created a
      mouse carrying a targeted mutation in the Dcx gene. Hemizygous male Dcx mice show
      severe postnatal lethality; the few that survive to adulthood are variably
      fertile. Dcx mutant mice show neocortical lamination that is largely
      indistinguishable from wild type and show normal patterns of neocortical
      neurogenesis and neuronal migration. In contrast, the hippocampus of both
      heterozygous females and hemizygous males shows disrupted lamination that is most
      severe in the CA3 region. Behavioral tests show defects in context and cued
      conditioned fear tests, suggesting that deficits in hippocampal learning
      accompany the abnormal cytoarchitecture.

PMID- 12196579
TI  - Neocortical long-term potentiation and long-term depression: site of expression
      investigated by infrared-guided laser stimulation.
AB  - The synaptic site of expression of long-term potentiation (LTP) and long-term
      depression (LTD) is still a matter of debate. To address the question of
      presynaptic versus postsynaptic expression of neocortical LTP and LTD in a direct
      approach, we measured the glutamate sensitivity of apical dendrites of layer 5
      pyramidal neurons during LTP and LTD. We used infrared-guided laser stimulation
      to release glutamate from its "caged" form with high spatial and temporal
      resolution. Responses to photolytically released glutamate and synaptically
      evoked EPSPs were recorded with patch-clamp pipettes from the neuronal somata.
      LTP and LTD could be induced by electrical stimulation at the same synapses in
      succession. The NMDA receptor-dependent LTD was accompanied by a decrease in the
      dendritic glutamate sensitivity, suggesting a postsynaptic expression of
      neocortical LTD. In contrast, LTP was never accompanied by a change in the
      dendritic glutamate sensitivity. A possible explanation for this finding is a
      presynaptic expression of neocortical LTP. Another set of experiments
      corroborated these results: Photolytic application of glutamate with a frequency
      of 5 Hz caused a long-lasting Ca2+ and NMDA receptor-dependent decrease in the
      dendritic glutamate sensitivity. In contrast, LTP of dendritic glutamate
      sensitivity was never induced by photostimulation, despite several experimental
      modifications to prevent washout of the induction mechanism and to induce a
      stronger postsynaptic Ca2+ influx. In conclusion, our findings provide strong
      evidence for a postsynaptic expression of neocortical LTD and favor a primarily
      presynaptic locus of neocortical LTP.

PMID- 12196580
TI  - Purinergic and muscarinic modulation of the cell cycle and calcium signaling in
      the chick retinal ventricular zone.
AB  - Spontaneous calcium transients occur in the ventricular zone of the chick retina
      and result from the endogenous release of neurotransmitters in the absence of
      action potentials. Calcium transients resulting from the activation of purinergic
      and muscarinic receptors occur in a mixed population of interphase and mitotic
      cells, whereas those produced by ionotropic GABA and glutamate receptors are
      mostly restricted to the interphase population, the GABA responses primarily
      coming from cells that express the neuronal marker TuJ-1. Muscarinic and
      purinergic receptors can act respectively as a brake and an accelerator on
      mitosis, whereas GABA and glutamate receptors are without effect. Our results
      suggest that the balance between muscarinic and purinergic activation acts to
      control the rate of retinal proliferation in early development.

PMID- 12196581
TI  - Brain-derived neurotrophic factor promotes the maturation of GABAergic mechanisms
      in cultured hippocampal neurons.
AB  - Brain-derived neurotrophic factor (BDNF) has been implicated in activity
      dependent plasticity of neuronal function and network arrangement. To clarify how
      BDNF exerts its action, we evaluated the physiological, histological, and
      biochemical characteristics of cultured hippocampal neurons after long-term
      treatment with BDNF. Here we show that BDNF facilitates high K(+)-elicited
      release of GABA but not of glutamate and induces an increase in immunoreactive
      signals of glutamic acid decarboxylase, a GABA-synthesizing enzyme. The soma size
      of GABAergic neurons was enlarged in BDNF-treated cultures, whereas the average
      soma size of all neurons was virtually unchanged. BDNF also upregulated protein
      levels of GABA(A) receptors but not of glutamate receptors. These data imply that
      BDNF selectively advances the maturation of GABAergic synapses. However,
      immunocytochemical analyses revealed that a significant expression of TrkB, a
      high-affinity receptor for BDNF, was detected in non-GABAergic as well as
      GABAergic neurons. BDNF also increased to total amount of synaptic vesicle
      associated proteins without affecting the number of presynaptic vesicles that can
      be labeled with FM1-43 after K(+) depolarization. Together, our findings indicate
      that BDNF principally promotes GABAergic maturation but may also potentially
      contribute to excitatory synapse development via increasing resting synaptic
      vesicles.

PMID- 12196582
TI  - Mammalian achaete scute homolog 2 is expressed in the adult sciatic nerve and
      regulates the expression of Krox24, Mob-1, CXCR4, and p57kip2 in Schwann cells.
AB  - The molecular control mechanisms and regulatory molecules involved in nerve
      repair are not yet well known. Schwann cells have been attributed an important
      role in peripheral nerve regeneration; therefore, attention has been drawn to
      regulatory factors expressed by these glial cells. Here, we demonstrate that
      Mash2, a basic helix-loop-helix (bHLH) transcription factor previously shown to
      be crucial for placenta development, is expressed by Schwann cells of adult
      peripheral nerves. We observed that this gene is downregulated after nerve lesion
      and, using cDNA array hybridization technology, we could demonstrate that Mash2
      is a regulator of Krox24, Mob-1, and CXCR4 expression in cultured Schwann cells.
      In addition, we provide strong evidence that Mash2 is a negative regulator of
      Schwann cell proliferation. Mash2 represents a first candidate for the missing
      class B bHLH proteins in peripheral nerves.

PMID- 12196583
TI  - Heterotopic neurons with altered inhibitory synaptic function in an animal model
      of malformation-associated epilepsy.
AB  - Children with brain malformations often exhibit an intractable form of epilepsy.
      Although alterations in cellular physiology and abnormal histology associated
      with brain malformations has been studied extensively, synaptic function in
      malformed brain regions remains poorly understood. We used an animal model, rats
      exposed to methylazoxymethanol (MAM) in utero, featuring loss of lamination and
      distinct nodular heterotopia to examine inhibitory synaptic function in the
      malformed brain. Previous in vitro and in vivo studies demonstrated an enhanced
      susceptibility to seizure activity and neuronal hyperexcitability in these
      animals. Here we demonstrate that inhibitory synaptic function is enhanced in
      rats exposed to MAM in utero. Using in vitro hippocampal slices and whole-cell
      voltage-clamp recordings from visualized neurons, we observed a dramatic
      prolongation of GABAergic IPSCs onto heterotopic neurons. Spontaneous IPSC decay
      time constants were increased by 195% and evoked IPSC decay time constants by
      220% compared with age-matched control CA1 pyramidal cells; no change in IPSC
      amplitude or rise time was observed. GABA transport inhibitors (tiagabine and NO
      711) prolonged evoked IPSC decay kinetics of control CA1 pyramidal cells (or
      normotopic cells) but had no effect on heterotopic neurons. Immunohistochemical
      staining for GABA transporters (GAT-1 and GAT-3) revealed a low level of
      expression in heterotopic cell regions, suggesting a reduced ability for GABA
      reuptake at these synapses. Together, our data demonstrate that GABA-mediated
      synaptic function at heterotopic synapses is altered and suggests that inhibitory
      systems are enhanced in the malformed brain.

PMID- 12196584
TI  - Differing mechanisms for glutamate receptor aggregation on dendritic spines and
      shafts in cultured hippocampal neurons.
AB  - We have explored the ability of axons from spinal and hippocampal neurons to
      aggregate NMDA- and AMPA-type glutamate receptors on each other as a way of
      exploring the molecular differences between their presynaptic elements. Spinal
      axons, which normally cluster only AMPA-type glutamate receptors on other spinal
      neurons, cluster both AMPA- and NMDA-type glutamate receptors on the dendritic
      shafts of hippocampal interneurons but are ineffective at clustering either
      subtype of glutamate receptor on the dendritic spines of hippocampal pyramidal
      neurons. Conversely, hippocampal axons appear to be multipotent, capable of
      clustering both AMPA- and NMDA-type glutamate receptors on hippocampal
      interneurons and pyramidal cells. The secretion of the neuronal activity
      regulated pentraxin (Narp) by hippocampal axons is restricted to contacts with
      interneurons. Exogenous application of Narp to cultured hippocampal neurons
      results in clusters of both NMDA- and AMPA-type glutamate receptors on
      hippocampal interneurons but not hippocampal pyramidal neurons. Because Narp
      displays no ability to directly aggregate NMDA receptors, we propose that Narp
      aggregates NMDA receptors in hippocampal interneurons indirectly through
      cytoplasmic coupling to synaptic AMPA receptors. Furthermore, our data suggest
      the existence of a novel molecule(s), capable of forming excitatory synapses on
      dendritic spines.

PMID- 12196585
TI  - Targeting axons to specific fiber tracts in vivo by altering cadherin expression.
AB  - In brain development, neurons have to be connected with specific postsynaptic
      neurons to establish functional neuronal circuits. Cadherins are cell adhesion
      molecules, which mark developing neuronal circuits. Each member of this class of
      molecules is expressed only on a restricted set of fiber fascicles that connect
      gray matter structures to form functional neural circuits. In view of their
      expression patterns, cadherins have been postulated to play a functional role in
      the proper establishment of fiber connections. We chose the chicken optic tectum
      to analyze the instructive potential of cadherins in axonal pathfinding. Three
      tectofugal pathways, the tectothalamic, tectobulbar, and tectoisthmic tracts,
      exit the dorsal mesencephalon via the brachium of the superior colliculus, a
      large fiber structure, which can be divided in specific subtracts that are
      characterized by the selective expression of N-cadherin, cadherin-7, cadherin-6B,
      or R-cadherin. By using in vivo electroporation, we overexpressed each of the
      cadherins in tectal projection neurons between embryonic days 6 and 11.
      Cotransfection with green fluorescent protein expression plasmid allowed us to
      assess the pathway choice, which the transgenic axons had made. Quantification
      based on confocal laser scanning microscopic images revealed that transgenic
      axons selectively fasciculated with tectofugal tracts specified by the matching
      type of cadherin. This is the first direct evidence that cadherins mediate
      differential axonal pathfinding in vivo, possibly by a preferentially homotypic
      adhesive mechanism.

PMID- 12196586
TI  - Distinct actions of Emx1, Emx2, and Pax6 in regulating the specification of areas
      in the developing neocortex.
AB  - The mammalian neocortex is organized into subdivisions referred to as areas that
      are distinguished from one another by differences in architecture, axonal
      connections, and function. The transcription factors EMX1, EMX2, and PAX6 have
      been proposed to regulate arealization. Emx1 and Emx2 are expressed by progenitor
      cells in a low rostrolateral to high caudomedial gradient across the embryonic
      neocortex, and Pax6 is expressed in a high rostrolateral to low caudomedial
      gradient. Recent evidence has suggested that EMX2 and PAX6 have a role in the
      genetic regulation of arealization. Here we use a panel of seven genes (Cad6,
      Cad8, Id2, RZRbeta, p75, EphA7, and ephrin-A5) representative of a broad range of
      proteins as complementary markers of positional identity to obtain a more
      thorough assessment of the suggested roles for EMX2 and PAX6 in arealization, and
      in addition to assess the proposed but untested role for EMX1 in arealization.
      Orderly changes in the size and positioning of domains of marker expression in
      Emx2 and Pax6 mutants strongly imply that rostrolateral areas (motor and
      somatosensory) are expanded, whereas caudomedial areas (visual) are reduced in
      Emx2 mutants and that opposite effects occur in Pax6 mutants, consistent with
      their opposing gradients of expression. In contrast, patterns of marker
      expression, as well as the distribution of area-specific thalamocortical
      projections, appear normal in Emx1 mutants, indicating that they do not exhibit
      changes in arealization. This lack of a defined role for EMX1 in arealization is
      supported by our finding of similar shifts in patterns of marker expression in
      Emx1; Emx2 double mutants as in Emx2 mutants. Thus, our findings indicate that
      EMX2 and PAX6 regulate, in opposing manners, arealization of the neocortex and
      impart positional identity to cortical cells, whereas EMX1 appears not to have a
      role in this process.

PMID- 12196587
TI  - Local and target-derived brain-derived neurotrophic factor exert opposing effects
      on the dendritic arborization of retinal ganglion cells in vivo.
AB  - The dendritic and axonal arbors of developing retinal ganglion cells (RGCs) are
      exposed to two sources of BDNF: RGC dendrites are exposed to BDNF locally within
      the retina, and RGC axons are exposed to BDNF at the target, the optic tectum.
      Our previous studies demonstrated that increasing tectal BDNF levels promotes RGC
      axon terminal arborization, whereas increasing retinal BDNF levels inhibits RGC
      dendritic arborization. These results suggested that differential neurotrophic
      action at the axon versus dendrite might be responsible for the opposing effects
      of BDNF on RGC axonal versus dendritic arborization. To explore this possibility,
      we examined the effects of altering BDNF levels at the optic tectum on the
      elaboration of RGC dendritic arbors in the retina. Increasing tectal BDNF levels
      resulted in a significant increase in dendritic branching, whereas neutralizing
      endogenous tectal BDNF with function-blocking antibodies significantly decreased
      dendritic arbor complexity. Thus, RGC dendritic arbors react in opposing manners
      to retinal- versus tectal-derived BDNF. Alterations in retinal BDNF levels,
      however, did not affect axon terminal arborization. Thus, RGC dendritic
      arborization is controlled in a complementary manner by both local and target
      derived sources of BDNF, whereas axon arborization is modulated solely by
      neurotrophic interactions at the target. Together, our results indicate that
      developing RGCs modulate dendritic arborization by integrating signals from
      discrete sources of BDNF in the eye and brain. Differential integration of
      spatially discrete neurotrophin signals within a single neuron may therefore
      finely tune afferent and efferent neuronal connectivity.

PMID- 12196588
TI  - Neuronal apoptosis associated with morphine tolerance: evidence for an opioid
      induced neurotoxic mechanism.
AB  - Tolerance to the analgesic effect of an opioid is a pharmacological phenomenon
      that occurs after its prolonged administration. Activation of the NMDA receptor
      (NMDAR) has been implicated in the cellular mechanisms of opioid tolerance.
      However, activation of NMDARs can lead to neurotoxicity under many circumstances.
      Here we demonstrate that spinal neuronal apoptosis was induced in rats made
      tolerant to morphine administered through intrathecal boluses or continuous
      infusion. The apoptotic cells were predominantly located in the superficial
      spinal cord dorsal horn, and most apoptotic cells also expressed glutamic acid
      decarboxylase, a key enzyme for the synthesis of the inhibitory neurotransmitter
      GABA. Consistently, increased nociceptive sensitivity to heat stimulation was
      observed in these same rats. Mechanistically, the spinal glutamatergic activity
      modulated morphine-induced neuronal apoptosis, because pharmacological
      perturbation of the spinal glutamate transporter activity or coadministration of
      morphine with the NMDAR antagonist (+)-5-methyl-10,11-dihydro-5H-dibenzo [a,d]
      cyclohepten-5,10-imine maleate affected both morphine tolerance and neuronal
      apoptosis. At the intracellular level, prolonged morphine administration resulted
      in an upregulation of the proapoptotic caspase-3 and Bax proteins but a
      downregulation of the antiapoptotic Bcl-2 protein in the spinal cord dorsal horn.
      Furthermore, coadministration with morphine of N-benzyloxycarbonyl-Val-Ala-Asp
      fluoromethyl ketone (a pan-caspase inhibitor) or acetyl-aspartyl-glutamyl-valyl
      aspart-1-aldehyde (a relatively selective caspase-3 inhibitor) blocked morphine
      induced neuronal apoptosis. Blockade of the spinal caspase-like activity also
      partially prevented morphine tolerance and the associated increase in nociceptive
      sensitivity. These results indicate an opioid-induced neurotoxic consequence
      regulated by the NMDAR-caspase pathway, a mechanism that may have clinical
      implications in opioid therapy and substance abuse.

PMID- 12196589
TI  - Untranslated element in neurofilament mRNA has neuropathic effect on motor
      neurons of transgenic mice.
AB  - Studies of experimental motor neuron degeneration attributable to expression of
      neurofilament light chain (NF-L) transgenes have raised the possibility that the
      neuropathic effects result from overexpression of NF-L mRNA, independent of NF-L
      protein effects (Canete-Soler et al., 1999). The present study was undertaken to
      test for an RNA-mediated pathogenesis. Transgenic mice were derived using either
      an enhanced green fluorescent protein reporter construct or modified chimeric
      constructs that differ only in their 3' untranslated regions (UTRs). Motor
      function and spinal cord histology were normal in mice expressing the unmodified
      reporter transgene. In mice expressing a chimeric transgene in which sequence of
      NF-L 3' UTR was inserted into the 3' UTR of the reporter transgene, we observed
      growth retardation and reduced kinetic activity during postnatal development.
      Older mice developed impairment of motor function and atrophy of nerve fibers in
      the ventral roots. A similar but more severe phenotype was observed when the
      chimeric transgene contained a 36 bp c-myc insert in an mRNA destabilizing
      element of the NF-L sequence. Our results suggest that neuropathic effects of
      overexpressing NF-L can occur at the level of transgene RNA and are mediated by
      sequences in the NF-L 3' UTR.

PMID- 12196590
TI  - Developmental changes underlying the formation of the specialized time coding
      circuits in barn owls (Tyto alba).
AB  - Barn owls are capable of great accuracy in detecting the interaural time
      differences (ITDs) that underlie azimuthal sound localization. They compute ITDs
      in a circuit in nucleus laminaris (NL) that is reorganized with respect to birds
      like the chicken. The events that lead to the reorganization of the barn owl NL
      take place during embryonic development, shortly after the cochlear and laminaris
      nuclei have differentiated morphologically. At first the developing owl's
      auditory brainstem exhibits morphology reminiscent of that of the developing
      chicken. Later, the two systems diverge, and the owl's brainstem auditory nuclei
      undergo a secondary morphogenetic phase during which NL dendrites retract, the
      laminar organization is lost, and synapses are redistributed. These events lead
      to the restructuring of the ITD coding circuit and the consequent reorganization
      of the hindbrain map of ITDs and azimuthal space.

PMID- 12196591
TI  - Adenosine induces inositol 1,4,5-trisphosphate receptor-mediated mobilization of
      intracellular calcium stores in basal forebrain cholinergic neurons.
AB  - In the cholinergic basal forebrain, we found previously that the extracellular
      adenosine concentration increase that accompanies sleep deprivation, acting via
      the A1 receptor, led to activation of the transcription factor nuclear factor
      kappaB and to the upregulation of A1 adenosine receptor mRNA. We thus began to
      examine intracellular signaling mechanisms. We report here that adenosine, acting
      in a dose-dependent manner and predominantly via A1 receptors, stimulated IP3
      receptor-regulated calcium release from intracellular stores. To the best of our
      knowledge, this calcium signaling pathway effect is a novel action of the G(i)
      coupled A1 adenosine receptor in neurons. Moreover, this calcium mobilization was
      not seen at all in noncholinergic neurons but was present in a large proportion
      of cholinergic neurons. These data suggest a potential role for a calcium
      signaling pathway in adenosine-induced long-term effects of sleep deprivation and
      a key role for cholinergic neurons in this process.

PMID- 12196592
TI  - Metabolic mapping of the effects of cocaine during the initial phases of self
      administration in the nonhuman primate.
AB  - Because most human studies of the neurobiological substrates of the effects of
      cocaine have been performed with drug-dependent subjects, little information is
      available about the effects of cocaine in the initial phases of drug use before
      neuroadaptations to chronic exposure have developed. The purpose of the present
      study, therefore, was to define the substrates that mediate the initial effects
      of cocaine in a nonhuman primate model of cocaine self-administration using the 2
      [14C]deoxyglucose method. Rhesus monkeys were trained to self-administer 0.03
      mg/kg per injection (N = 4) or 0.3 mg/kg per injection (N = 4) cocaine and
      compared with monkeys trained to respond under an identical schedule of food
      reinforcement (N = 4). Monkeys received 30 reinforcers per session, and metabolic
      mapping was conducted at the end of the fifth self-administration session.
      Cocaine self-administration reduced glucose utilization in the mesolimbic system,
      including the ventral tegmental area, ventral striatum, and medial prefrontal
      cortex. In addition, metabolic activity was increased in the dorsolateral and
      dorsomedial prefrontal cortex, as well as in the mediodorsal nucleus of the
      thalamus. These latter effects are distinctly different from those seen after the
      noncontingent administration of cocaine, suggesting that self-administration
      engages circuits beyond those engaged merely by the pharmacological actions of
      cocaine. The involvement of cortical areas subserving working memory suggests
      that strong associations between cocaine and the internal and external
      environment are formed from the very outset of cocaine self-administration. The
      assessment of the effects of cocaine at a time not readily evaluated in humans
      provides a baseline from which the effects of chronic cocaine exposure can be
      investigated.

PMID- 12196593
TI  - Anatomical, physiological, and pharmacological characteristics of histidine
      decarboxylase knock-out mice: evidence for the role of brain histamine in
      behavioral and sleep-wake control.
AB  - The hypothesis that histaminergic neurons are involved in brain arousal is
      supported by many studies. However, the effects of the selective long-term
      abolition of histaminergic neurons on the sleep-wake cycle, indispensable in
      determining their functions, remain unknown. We have compared brain histamine(HA)
      immunoreactivity and the cortical-EEG and sleep-wake cycle under baseline
      conditions or after behavioral or pharmacological stimuli in wild-type (WT) and
      knock-out mice lacking the histidine decarboxylase gene (HDC-/-). HDC-/-mice
      showed an increase in paradoxical sleep, a decrease in cortical EEG power in
      theta-rhythm during waking (W), and a decreased EEG slow wave sleep/W power
      ratio. Although no major difference was noted in the daily amount of spontaneous
      W, HDC-/-mice showed a deficit of W at lights-off and signs of somnolence, as
      demonstrated by a decreased sleep latencies after various behavioral stimuli,
      e.g., WT-mice placed in a new environment remained highly awake for 2-3 hr,
      whereas HDC-/-mice fell asleep after a few minutes. These effects are likely to
      be attributable to lack of HDC and thus of HA. In WT mice, indeed,
      intraperitoneal injection of alpha-fluoromethylhistidine (HDC-inhibitor) caused a
      decrease in W, whereas injection of ciproxifan (HA-H3 receptor antagonist)
      elicited W. Both injections had no effect in HDC-/-mice. Moreover, PCR and
      immunohistochemistry confirmed the absence of the HDC gene and brain HA
      immunoreactive neurons in the HDC-/-mice. These data indicate that disruption of
      HA-synthesis causes permanent changes in the cortical-EEG and sleep-wake cycle
      and that, at moments when high vigilance is required (lights off, environmental
      change em leader ), mice lacking brain HA are unable to remain awake, a
      prerequisite condition for responding to behavioral and cognitive challenges. We
      suggest that histaminergic neurons also play a key role in maintaining the brain
      in an awake state faced with behavioral challenges.

PMID- 12196594
TI  - Diverse synaptic mechanisms generate direction selectivity in the rabbit retina.
AB  - The synaptic conductance of the On-Off direction-selective ganglion cells was
      measured during visual stimulation to determine whether the direction selectivity
      is a property of the circuitry presynaptic to the ganglion cells or is generated
      by postsynaptic interaction of excitatory and inhibitory inputs. Three synaptic
      asymmetries were identified that contribute to the generation of direction
      selective responses: (1) a presynaptic mechanism producing stronger excitation in
      the preferred direction, (2) a presynaptic mechanism producing stronger
      inhibition in the opposite direction, and (3) postsynaptic interaction of
      excitation with spatially offset inhibition. Although the on- and off-responses
      showed the same directional tuning, the off-response was generated by all three
      mechanisms, whereas the on-response was generated primarily by the two
      presynaptic mechanisms. The results indicate that, within a single neuron,
      different strategies are used within distinct dendritic arbors to accomplish the
      same neural computation.

PMID- 12196595
TI  - A real-time state predictor in motor control: study of saccadic eye movements
      during unseen reaching movements.
AB  - Theoretical motor control predicts that because of delays in sensorimotor
      pathways, a neural system should exist in the brain that uses efferent copy of
      commands to the arm, sensory feedback, and an internal model of the dynamics of
      the arm to predict the future state of the hand (i.e., a forward model). We
      tested this theory under the hypothesis that saccadic eye movements, tracking an
      unseen reaching movement, would reflect the output of this state predictor. We
      found that in unperturbed reaching movements, saccade occurrence at any time t
      consistently provided an unbiased estimate of hand position at t + 196 msec. To
      investigate the behavior of this predictor during feedback error control, we
      applied 50 msec random-force perturbations to the moving hand. Saccades showed a
      sharp inhibition at 100 msec after perturbation. At approximately 170 msec, there
      was a sharp increase in saccade probabilities. These postperturbation saccades
      were an unbiased estimator of hand position at saccade time t + 150 msec. The
      ability of the brain to guide saccades to the future position of the hand failed
      when a force field unexpectedly changed the dynamics of the hand immediately
      after perturbation. The behavior of the eyes suggested that during reaching
      movements, the brain computes an estimate of future hand position based on an
      internal model that relies on real-time proprioceptive feedback. When an error
      occurs in reaching movements, the estimate of future hand position is recomputed.
      The saccade inhibition period that follows the hand perturbation may indicate the
      length of time it takes for this computation to take place.

PMID- 12196596
TI  - Substance P (neurokinin 1) receptor antagonists enhance dorsal raphe neuronal
      activity.
AB  - Substance P receptor [neurokinin 1 (NK1] antagonists (SPAs) represent a novel
      mechanistic approach to antidepressant therapy with comparable clinical efficacy
      to selective serotonin reuptake inhibitors (SSRIs). Because SSRIs are thought to
      exert their therapeutic effects by enhancing central serotonergic function, we
      have examined whether SPAs regulate neuronal activity in the dorsal raphe nucleus
      (DRN), the main source of serotonergic projections to the forebrain. Using in
      vivo electrophysiological techniques in the guinea pig, we found that
      administration of the highly selective NK1 receptor antagonist 1-(5-[[(2R,3S)-2
      ([(1R)-1-[3,5-bis(trifluoromethyl)phenyl]ethyl]oxy)-3-(4-phenyl)morpholin-4
      yl]methyl]-2H-1,2,3-triazol-4-yl)-N,N-dimethylmethanamine (L-760735) caused an
      increase in DRN neuronal firing rate. However, unlike chronic treatment with
      fluoxetine, there was no detectable 5-HT1A autoreceptor desensitization. In vitro
      electrophysiological investigation showed that these effects were not mediated by
      a direct action in the DRN, an observation supported by immunocytochemical
      analysis that identified the lateral habenula (LHb) as a more likely site of
      action. Subsequently, we found that local application of L-760735 into the LHb
      increased firing in the DRN, which, together with our data showing that L-760735
      increased metabolic activity in the cingulate cortex, amygdala, LHb, and DRN,
      indicates that the effects of L-760735 may be mediated by disinhibition of
      forebrain structures acting via a habenulo raphe projection. These findings
      support other evidence for an antidepressant profile of SPAs and suggest that
      regulation of DRN neuronal activity may contribute to their antidepressant
      mechanism of action but in a manner that is distinct from monoamine reuptake
      inhibitors.

PMID- 12196597
TI  - Phosphorylation of extracellular signal-regulated kinase in primary afferent
      neurons by noxious stimuli and its involvement in peripheral sensitization.
AB  - Alteration in the intracellular signal transduction pathway in primary afferent
      neurons may contribute to pain hypersensitivity. We demonstrated that very rapid
      phosphorylation of extracellular signal-regulated protein kinases (pERK) occurred
      in DRG neurons that were taking part in the transmission of various noxious
      signals. The electrical stimulation of Adelta fibers induced pERK primarily in
      neurons with myelinated fibers. c-Fiber activation by capsaicin injection induced
      pERK in small neurons with unmyelinated fibers containing vanilloid receptor-1
      (VR-1), suggesting that pERK labeling in DRG neurons is modality specific.
      Electrical stimulation at the c-fiber level with different intensities and
      frequencies revealed that phosphorylation of ERK is dependent on the frequency.
      We examined the pERK in the DRG after application of natural noxious stimuli and
      found a stimulus intensity-dependent increase in labeled cell size and in the
      number of activated neurons in the c- and Adelta-fiber population.
      Immunohistochemical double labeling with phosphorylated ERK/VR-1 and
      pharmacological study demonstrated that noxious heat stimulation induced pERK in
      primary afferents in a VR-1-dependent manner. Capsaicin injection into the skin
      also increased pERK labeling significantly in peripheral fibers and terminals in
      the skin, which was prevented by a mitogen-activated protein kinase/ERK kinase
      inhibitor, 1,4-diamino-2,3-dicyano-1,4-bis(2-aminopheylthio)butadiene (U0126).
      Behavioral experiments showed that U0126 dose-dependently attenuated thermal
      hyperalgesia after capsaicin injection and suggested that the activation of ERK
      pathways in primary afferent neurons is involved in the sensitization of primary
      afferent neurons. Thus, pERK in primary afferents by noxious stimulation in vivo
      showed distinct characteristics of expression and may be correlated with the
      functional activity of primary afferent neurons.

PMID- 12196598
TI  - Degeneration of myelinated efferent fibers induces spontaneous activity in
      uninjured C-fiber afferents.
AB  - We demonstrated recently that uninjured C-fiber nociceptors in the L4 spinal
      nerve develop spontaneous activity after transection of the L5 spinal nerve. We
      postulated that Wallerian degeneration leads to an alteration in the properties
      of the neighboring, uninjured afferents from adjacent spinal nerves. To explore
      the role of degeneration of myelinated versus unmyelinated fibers, we
      investigated the effects of an L5 ventral rhizotomy in rat. This lesion leads to
      degeneration predominantly in myelinated fibers. Mechanical paw-withdrawal
      thresholds were assessed with von Frey hairs, and teased-fiber techniques were
      used to record from single C-fiber afferents in the L4 spinal nerve. Behavioral
      and electrophysiological data were collected in a blinded manner. Seven days
      after surgery, a marked decrease in withdrawal thresholds was observed after the
      ventral rhizotomy but not after the sham operation. Single fiber recordings
      revealed low-frequency spontaneous activity in 25% of the C-fiber afferents 8-10
      d after the lesion compared with only 11% after sham operation. Paw-withdrawal
      thresholds were inversely correlated with the incidence of spontaneous activity
      in high-threshold C-fiber afferents. In normal animals, low-frequency
      electrocutaneous stimulation at C-fiber, but not A-fiber, strength produced
      behavioral signs of secondary mechanical hyperalgesia on the paw. These results
      suggest that degeneration in myelinated efferent fibers is sufficient to induce
      spontaneous activity in C-fiber afferents and behavioral signs of mechanical
      hyperalgesia. Ectopic spontaneous activity from injured afferents was not
      required for the development of the neuropathic pain behavior. These results
      provide additional evidence for a role of Wallerian degeneration in neuropathic
      pain.

PMID- 12196599
TI  - Hypocretin increases impulse flow in the septohippocampal GABAergic pathway:
      implications for arousal via a mechanism of hippocampal disinhibition.
AB  - Hypocretins (Hcrts), or orexins, are a recently described set of hypothalamic
      peptides that have been implicated in feeding, neuroendocrine regulation, sleep
      wakefulness, and disorders of sleep, such as narcolepsy. Hcrt-containing neurons,
      which are located exclusively in the lateral hypothalamic area, provide a dense
      innervation to the medial septum/diagonal band of Broca (MSDB), a sleep
      associated brain region that has been suggested to show intense axonal
      degeneration in canine narcoleptics. The MSDB, via its cholinergic and GABAergic
      projections to the hippocampus, controls the hippocampal theta rhythm and
      associated learning and memory functions that occur during exploratory behavior
      and rapid eye movement sleep. Neurons of the MSDB express the Hcrt receptor 2,
      which is mutated in canine narcoleptics, but lack the Hcrt receptor 1 mRNA. In
      the present study, we investigated the electrophysiological effects of Hcrt2 on
      MSDB neurons from rat brain slices. We report that Hcrt2 produces a reversible,
      reproducible, concentration-dependent and direct postsynaptic excitation of GABA
      type neurons of the MSDB with an EC50 of 207 nm. This effect is sodium dependent
      but not potassium or chloride dependent and is attenuated by blockers of the Na+
      Ca+ exchanger. Hcrt2 also increases impulse-dependent release of GABA within the
      MSDB. Using recordings from retrogradely labeled septohippocampal neurons, we
      found that Hcrt2-excited MSDB neurons project to the hippocampus and have a
      GABAergic physiological signature. Double-immunolabeling studies confirmed the
      presence of Hcrt receptor-2 immunoreactivity in septohippocampal GABAergic
      neurons, as well as the presence of Hcrt fibers adjacent to these neurons. Based
      on these results, we speculate that Hcrt2-induced activation of septohippocampal
      GABAergic neurons will, by engaging disinhibitory mechanisms in the hippocampus,
      promote generation of the hippocampal theta rhythm and associated behaviors.

PMID- 12196600
TI  - Activation of a cortical column by a thalamocortical impulse.
AB  - Thalamocortical (TC) impulses potently influence the sensory neocortex, but the
      functional impact of individual TC neurons throughout the layers of the cortex
      has proved difficult to assess. Here we examine, in awake rabbits, the vertical
      distribution of monosynaptic currents generated in a somatosensory cortical
      "barrel" column by spontaneous impulses of single, topographically aligned TC
      neurons. We show that closely neighboring TC neurons generate widely differing
      patterns of monosynaptic activation within layers 4 and 6 of their aligned
      column. Moreover, synaptic currents generated by TC impulses with long preceding
      interspike intervals are greatly enhanced in both of these layers. The degree of
      this enhancement differs reliably among neighboring TC neurons but, for a given
      neuron, is very similar in layers 4 and 6. Our results indicate that in the awake
      state, TC synapses throughout the depth of the cortex serve as powerful filters
      of sensory information that reflect individual characteristics of their parent TC
      neuron.

PMID- 12196601
TI  - Vocal memory and learning in adult Bengalese Finches with regenerated hair cells.
AB  - Critical learning periods are common in vertebrate development. In many birds,
      song learning is limited by a critical period; juveniles copy songs from adult
      birds by forming memories of those songs during a restricted developmental period
      and then using auditory feedback to practice their own vocalizations. Adult songs
      are stable over time regardless of exposure to other birds, but auditory feedback
      is required for the maintenance of stable adult song. A technique was developed
      to reversibly deafen Bengalese Finches by destruction and regeneration of inner
      ear auditory hair cells. With this approach, we asked two questions about the
      plasticity of song information stored in the adult brain. First, do adult birds
      store memories or "templates" of their songs that exist independent of auditory
      reinforcement? Such memories could be used to control vocal output by acting as
      fixed models of song to which ongoing vocalizations are matched. Second, can
      adult song learning, which does not normally occur in this species, be induced by
      removing and then restoring hearing? Studying changes in adult song behavior
      during hair cell loss and regeneration revealed two findings: (1) adult birds
      store memories or templates of their songs that exist independent of auditory
      input and can be used to restore normal vocal behavior when hearing is restored;
      (2) under experimental circumstances, adult birds can be induced to acquire song
      material from other birds. Results suggest that, in Bengalese Finches, the degree
      of behavioral and neural plasticity in juvenile and adult birds may be less
      distinct that previously thought.

PMID- 12196602
TI  - Local injection of a selective endothelin-B receptor agonist inhibits endothelin
      1-induced pain-like behavior and excitation of nociceptors in a naloxone
      sensitive manner.
AB  - We showed previously that subcutaneous injection of the injury-associated peptide
      mediator endothelin-1 (ET-1) into the rat plantar hindpaw produces pain behavior
      and selective excitation of nociceptors, both through activation of ET(A)
      receptors likely on nociceptive terminals. The potential role of ET(B) receptor
      activation in these actions of ET-1-has not been examined. Therefore, in these
      experiments, we studied the effect of blocking or activating ET(B) receptors on
      ET-1-induced hindpaw flinching and excitation of nociceptors in rats. An ET(B)
      receptor-selective antagonist, BQ-788 (3 mm), coinjected with ET-1 (200 microm)
      reduced the time-to-peak of flinching and significantly enhanced the average
      maximal flinch frequency (MFF). In contrast, coinjection of an ET(B) receptor
      selective agonist, IRL-1620 (100 or 200 microm), with ET-1 reduced the average
      MFF and the average total number of flinches. Interestingly, this unexpected
      inhibitory effect of IRL-1620 was prevented by the nonselective opioid receptor
      antagonist naloxone (2.75 mm). To confirm these inhibitory actions, we studied
      the effects of IRL-1620 on ET-1-induced spike responses in single,
      physiologically characterized nociceptive C-fibers. IRL-1620 suppressed spike
      responses to ET-1 in all (n = 12) C-units, with mean and maximum response
      frequencies of 0.08 +/- 0.02 and 1.5 +/- 0.4 impulses/sec versus 0.32 +/- 0.07
      and 4.17 +/- 0.17 impulses/sec for ET-1 alone. In additional support of the
      behavioral results, coinjection of naloxone (2.75 mm) completely prevented this
      inhibitory action of IRL-1620. These results establish that ET(B) receptor
      activation inhibits ET-1-induced pain behavior and nociception in a naloxone
      sensitive manner and point to a previously unrecognized dual modulation of acute
      nociceptive signaling by ET(A) and ET(B) receptors in cutaneous tissues.

PMID- 12196604
TI  - Conceptual, spatial, and cue learning in the Morris water maze in fast or slow
      kindling rats: attention deficit comorbidity.
AB  - Rat lines selectively bred for differences in amygdala excitability, manifested
      by "fast" or "slow" kindling epileptogenesis, display several comorbid features
      related to anxiety and learning. To assess the nature of the learning deficits in
      fast kindling rats, performance was evaluated in several variants of a Morris
      water-maze test. Regardless of whether the location of the platform was fixed or
      varied over days (matching-to-place task), the fast rats displayed inferior
      performance, suggesting both working and reference memory impairments.
      Furthermore, when the position of the platform was altered after the response was
      acquired, fast rats were more persistent in emitting the previously acquired
      response. The poor performance of fast rats was also evident in both cued and
      uncued tasks, indicating that their disturbed learning was not simply a
      reflection of a spatial deficit. Moreover, fast rats could be easily distracted
      by irrelevant cues, suggesting that these animals suffered from an attentional
      disturbance. Interestingly, when rats received several training trials with the
      platform elevated, permitting them to develop the concept of facile escape, the
      performance of fast rats improved greatly. The performance disturbance in fast
      rats may reflect difficulties in forming a conceptual framework under conditions
      involving some degree of ambiguity, as well as greater distractibility by
      irrelevant cues. These various attributes of the fast rats may serve as a
      potentially useful animal model of disorders characterized by an attention
      deficit.

PMID- 12196603
TI  - Identification and characterization of the feeding circuit-activating peptides, a
      novel neuropeptide family of aplysia.
AB  - We use a multidisciplinary approach to identify, map, and characterize the
      bioactivity of modulatory neuropeptides in the circuitry that generates feeding
      behavior in Aplysia. Matrix-assisted laser desorption/ionization time-of-flight
      mass spectrometry of the cerebral-buccal connective (CBC), a nerve containing
      axons of many interneurons that control feeding behavior of Aplysia, was used to
      identify neuropeptides that may participate in generation and shaping of feeding
      motor programs. Using this functionally oriented search, we identified a novel
      family of peptides that we call the feeding circuit-activating peptides (FCAPs).
      Two peptides with masses identical to those observed in the CBCs (molecular
      weight 1387 and 1433) were purified from buccal ganglia and partially sequenced
      using mass spectrometry. The amino acid sequence was then used to clone the FCAP
      precursor, which encodes multiple copies of eight different FCAPs. The two FCAPs
      present in highest copy number correspond to those observed in the CBC. The
      distribution of FCAP expression was mapped using Northern analysis, whole-mount
      in situ hybridization, and immunocytochemistry. Consistent with our initial
      findings, FCAP-immunopositive axons were observed in the CBC. Furthermore, we
      found that FCAP was present in some cerebral-buccal and buccal-cerebral
      interneurons. As their name suggests, FCAPs are capable of initiating rhythmic
      feeding motor programs and are the first neuropeptides with such activity in this
      circuit. The actions of FCAPs suggest that these peptides may contribute to the
      induction and maintenance of food-induced arousal. FCAPs were also localized to
      several other neuronal systems, suggesting that FCAPs may play a role in the
      regulation of multiple behaviors.

PMID- 12196605
TI  - Facilitation of monosynaptic and complex PSPs in type I interneurons of
      conditioned Hermissenda.
AB  - Synaptic plasticity and intrinsic changes in neuronal excitability are two
      mechanisms for Pavlovian conditioning. Pavlovian conditioning of Hermissenda
      produces synaptic facilitation of monosynaptic medial B-medial A IPSPs and
      intrinsic changes in excitability of type A and B cells in isolated and intact
      sensory neurons of the conditioned stimulus (CS) pathway. Recently two types of
      interneurons that receive either excitatory or inhibitory monosynaptic or
      polysynaptic input from photoreceptors have been identified. On the basis of
      morphological and electrophysiological criteria, the interneurons have been
      classified as type I(e), I(i) (direct), and type II(e), II(i) (indirect). We have
      now examined synaptic facilitation of monosynaptic PSPs in type I(e) and I(i)
      interneurons after conditioning and pseudorandom control procedures. Here we
      report that CS-elicited spike activity is increased in type I(e) interneurons and
      decreased in type I(i) interneurons of conditioned animals relative to their
      respective baseline activity and pseudorandom control groups. Classical
      conditioning resulted in synaptic facilitation of type I(e) and I(i) monosynaptic
      PSPs elicited by lateral B spikes and enhancement of the amplitude of complex
      PSPs elicited by the CS. These results provide additional sites of plasticity in
      the neural circuit involved with the expression of learned behavior produced by
      Pavlovian conditioning of Hermissenda.

PMID- 12196606
TI  - Abnormal cerebellar signaling induces dystonia in mice.
AB  - Dystonia is a relatively common neurological syndrome characterized by twisting
      movements or sustained abnormal postures. Although the basal ganglia have been
      implicated in the expression of dystonia, recent evidence suggests that abnormal
      cerebellar function is also involved. In these studies, a novel mouse model was
      developed to study the role of the cerebellum in dystonia. Microinjection of low
      doses of kainic acid into the cerebellar vermis of mice elicited reliable and
      reproducible dystonic postures of the trunk and limbs. The severity of the
      dystonia increased linearly with kainate dose. Kainate-induced dystonia was
      blocked by the glutamatergic antagonist 1,2,3,4-tetrahydro-6-nitro-2,3-dioxo
      benzo[f]quinoxaline-7-sulfonamide and reproduced by domoic acid microinjection,
      suggesting that the induction of dystonia is dependent on glutamatergic
      activation in this model. The abnormal movements were not associated with kainate
      induced seizures, because EEG recordings showed no epileptiform activity during
      the dystonic events. Neuronal activation, as assessed by in situ hybridization
      for c-fos, revealed c-fos mRNA expression in the cerebellum, locus ceruleus, and
      red nucleus. In contrast, regions associated with epileptic seizures, such as the
      hippocampus, did not exhibit increased c-fos expression after cerebellar kainate
      injection. Furthermore, in transgenic mice lacking Purkinje cells, significantly
      less dystonia was induced after kainic acid injection, implicating Purkinje cells
      and the cerebellar cortex in this model of dystonia. Together, these data suggest
      that abnormal cerebellar signaling produces dystonia and that the cerebellum
      should be considered along with the basal ganglia in the pathophysiology of this
      movement disorder.

PMID- 12196608
TI  - Reconsidering health disparities.

PMID- 12196609
TI  - A call to action.

PMID- 12196610
TI  - Reducing health disparities through community-based research.

PMID- 12196611
TI  - A collaborative effort to enhance HIV/STI screening in five county jails.
AB  - Funding from the Centers for Disease Control and Prevention and the Health
      Resources and Services Administration (HRSA) supports collaborations among health
      departments (CA, FL, GA, IL, MA, NJ, NY), correctional facilities, and community
      based organizations to improve services to HIV-infected inmates, particularly as
      they return to the community. Additionally, HRSA funded the Evaluation and
      Program Support Center to guide the implementation of a multi-site evaluation of
      the Corrections Demonstration Project (CDP). The authors present a model approach
      to the problem of health disparities that involves forging collaborations among
      federal funders, public health departments, corrections, community-based
      organizations, and the scientific research community. They show how such
      collaboration can promote the reduction of racial/ethnic health disparities. The
      authors examined disease screening activities in five county jails. Screening for
      HIV and other sexually transmitted infections (STIs) was offered during the
      medical intake process and during HIV prevention education sessions. One thousand
      twenty inmates were tested from July 1, 2000, through December 31, 2000, for HIV
      infection, and 171 (17%) positive cases were identified (largely due to
      confirmatory testing). Of HIV-positive inmates, 83 (49%) were started on
      antiretroviral treatment. Additionally, 2,160 were tested for chlamydia, 1,327
      for gonorrhea (largely duplicated), and 937 (duplicated) for syphilis. Across all
      three STIs, 78% of those who tested positive were treated. The remaining 22%
      either declined treatment, were released prior to notification of results, or
      were released prior to starting treatment. The CDP offers a model approach for
      addressing the poor health status of members of racial/ethnic minority groups by
      developing collaborations between corrections, public health departments,
      community-based organizations, and academia. An outgrowth of this collaboration
      is the improved capacity to detect and treat disease, which is a necessary
      component of a comprehensive HIV risk reduction program.

PMID- 12196612
TI  - Collaboration among community members, local health service providers, and
      researchers in an urban research center in Harlem, New York.
AB  - The Urban Research Center at the Center for Urban Epidemiologic Studies brings
      together community members and researchers working in Harlem, New York. A
      Community Advisory Board (CAB) composed of community members, service providers,
      public health professionals, and researchers was formed to assist the Center's
      research and interventions and to guide community partnerships. Through a
      collaborative process, the CAB identified three public health problems-substance
      use, infectious diseases, and asthma-as action priorities. To deal with substance
      use, the Center created a Web-based resource guide for service providers and a
      "survival guide" for substance users, designed to improve access to community
      services. To deal with infectious diseases, the Center is collaborating with
      local community-based organizations on an intervention that trains injection drug
      users to serve as peer mentors to motivate behavior change among other injection
      drug users. To deal with asthma, the Center is collaborating with community child
      care providers on an educational intervention to increase asthma awareness among
      day care teaching staff, enhance communication between staff and families, and
      improve the self-management skills of children with asthma. The Center's
      experience has demonstrated that active communities and responsive researchers
      can establish partnerships that improve community health.

PMID- 12196613
TI  - Trust and collaboration in the prevention of sexually transmitted diseases.
AB  - High rates of sexually transmitted diseases (STDs) are sustained in communities
      by a relatively small group of people, referred to as the core of transmission.
      Definitions of the core vary but inevitably include people who are socially
      marginalized and who distrust people in authority, such as public health
      practitioners and university researchers. Having an effect on a marginalized
      group usually depends on effective collaboration with people they trust.
      Researchers from the University of North Carolina School of Public Health
      developed a trust-based collaboration with community members of a rural county in
      North Carolina to implement an STD prevention program that, in turn, relied on
      trust in local social networks. As part of the STD prevention demonstration
      project, the research team established a community resource group made up of
      local African Americans who helped design, implement, and evaluate the
      intervention. The group identified 21 women to whom others in the community
      turned for advice on sex and STDs. These women were trained as lay health
      advisors to disseminate information and skills for preventing STDs among their
      social networks. Through face-to-face structured interviews before and after the
      intervention, the authors measured improvements in STD treatment and prevention
      behaviors. The proportion of people practicing each of the targeted behaviors
      improved during the evaluation period. In addition to disseminating information
      through their own social networks, the lay health advisors demonstrated new
      skills and a desire to interact with local care providers to influence the
      provision of care for STDs for low-income African Americans in this county. Each
      participant in the collaboration played a role in establishing or building upon
      trust with others. These trusting relationships were critical for empowering a
      marginalized group at high risk for STDs.

PMID- 12196614
TI  - The East Side Village Health Worker Partnership: integrating research with action
      to reduce health disparities.
AB  - This article describes the work of the East Side Village Health Worker
      Partnership as a case study of an initiative that seeks to reduce the
      disproportionate health risks experienced by residents of Detroit's east side.
      The Partnership is a community-based participatory research and intervention
      collaboration among academia, public health practitioners, and the east side
      Detroit community. The Partnership is guided by a steering committee that is
      actively involved in all aspects of the research, intervention, and dissemination
      process, made up of representatives of five community-based organizations,
      residents of Detroit's east side, the local health department, a managed care
      provider, and an academic institution. The major goal of the East Side Village
      Health Worker Partnership is to address the social determinants of health on
      Detroit's east side, using a lay health advisor intervention approach. Data
      collected from 1996 to 2001 are used here to describe improvements in research
      methods, practice activities, and community relationships that emerged through
      this academic-practice-community linkage.

PMID- 12196615
TI  - Collaborative research and action to control the geographic placement of outdoor
      advertising of alcohol and tobacco products in Chicago.
AB  - Community activists in Chicago believed their neighborhoods were being targeted
      by alcohol and tobacco outdoor advertisers, despite the Outdoor Advertising
      Association of America's voluntary code of principles, which claims to restrict
      the placement of ads for age-restricted products and prevent billboard saturation
      of urban neighborhoods. A research and action plan resulted from a 10-year
      collaborative partnership among Loyola University Chicago, the American Lung
      Association of Metropolitan Chicago (ALAMC), and community activists from a
      predominately African American church, St. Sabina Parish. In 1997 Loyola
      University and ALAMC researchers conducted a cross-sectional prevalence survey of
      alcohol and tobacco outdoor advertising. Computer mapping was used to locate all
      4,247 licensed billboards in Chicago that were within 500- and 1,000-foot
      radiuses of schools, parks, and playlots. A 50% sample of billboards was visually
      surveyed and coded for advertising content. The percentage of alcohol and tobacco
      billboards within the 500- and 1,000-foot zones ranged from 0% to 54%. African
      American and Hispanic neighborhoods were disproportionately targeted for outdoor
      advertising of alcohol and tobacco. Data were used to convince the Chicago City
      Council to pass one of the nation's toughest anti-alcohol and tobacco billboard
      ordinances, based on zoning rather than advertising content. The ordinance was
      challenged in court by advertisers. Recent Supreme Court rulings made enactment
      of local billboard ordinances problematic. Nevertheless, the research, which
      resulted in specific legislative action, demonstrated the importance of linkages
      among academic, practice, and grassroots community groups in working together to
      diminish one of the social causes of health disparities.

PMID- 12196616
TI  - Behavioral interventions for the control of tuberculosis among adolescents.
AB  - OBJECTIVES: Activation of latent tuberculosis infection into tuberculosis disease
      (TB), the primary killer among infectious diseases worldwide, can be prevented
      with six months of anti-TB medication. A large percentage of adolescents started
      on medication, however, fail to complete their treatment. The authors developed
      and tested the effects of innovative educational strategies on infected
      adolescents at two health centers serving ethnically diverse populations.
      METHODS: The authors used a randomized experimental four-group design to assess
      the independent and combined effects of peer counseling and a participant-parent
      contingency contract intervention. RESULTS: A total of 794 adolescents were
      recruited into the study, for a 79% participation rate. The overall rate of
      treatment completion was 79.8%. Self-efficacy for medication-taking behavior at
      post-test correlated strongly with completion of care (R = 0.367, p = 0.002).
      Participants randomized to the peer counseling groups demonstrated significantly
      greater improvements in self-efficacy and mastery than the usual care control
      group. Based on the study results, continuing education seminars and workshops
      were implemented for TB control staff at the two health clinics and for all TB
      Control Division staff at the Los Angeles County Health Department. Educational
      materials and a training manual for enhancing completion of treatment of latent
      TB infection through tailored educational approaches were developed and
      disseminated to the clinics. CONCLUSIONS: Health education and incentives are
      helpful adjuncts to the completion of treatment for latent tuberculosis infection
      in adolescents.

PMID- 12196618
TI  - A collaborative program between a school of public health and a local health
      department to increase HIV testing of pregnant women.
AB  - OBJECTIVE: This study evaluates the effectiveness of a continuing medical
      education (CME) program that sought to increase HIV testing of women attending
      maternity clinics of the City of Houston Department of Health and Human Services
      (HDHHS). The CME program consisted of 14 training sessions given in 1995, 1996,
      1997, 1999, and 2000. Educational objectives included increasing patient
      knowledge of HIV perinatal testing, increasing patient appreciation of the
      importance of HIV testing, and developing staff skills in educating and
      counseling women to accept HIV testing during pregnancy. METHODS: The CME program
      was based on assessment of clinician learning needs and an algorithm of the
      testing process, both jointly developed by faculty from the University of Texas
      Health Science Center at Houston School of Public Health and HDHHS personnel. The
      algorithm was also used to assess the care delivered. The CME was evaluated by
      examining changes in the percentage of women tested in the maternity clinics.
      RESULTS: In 1995, the year before the education program, 5.7% of women seen in
      the maternity clinics were tested for HIV. After the program began, testing rates
      rose to 64.2% in 1996, 65.5% in 1997, and 43.3% in 1998. Given the decline in
      testing in 1998, additional CME sessions were conducted in 1999-2000. The rate of
      testing rose to 62.3% in 1999 and 76.5% in 2000. CONCLUSION: Cooperative planning
      between university and health department personnel can create CME programs that
      alter provider behaviors and service delivery patterns to increase HIV testing.
      Outcomes need to be regularly monitored, however, to determine the need for
      maintenance or performance reinforcement.

PMID- 12196617
TI  - A community-based collaboration to assess and improve medical insurance status
      and access to health care of Latino children.
AB  - OBJECTIVES: Despite eligibility for subsidized insurance, low-income Latino
      children are at high risk of being medically uninsured. The authors sought to
      understand and improve access to medical insurance for Latino children living in
      a California community of predominantly low-income immigrant families. METHODS:
      During the summer of 1999, trained women from the community conducted interviews
      in Spanish with 252 randomly selected mothers of 464 children younger than age
      19. Mothers provided information about family demographics, children's medical
      insurance, health care access, and experiences obtaining and maintaining
      children's insurance. RESULTS: Most children (83.3%) were eligible for subsidized
      medical insurance (48.4% Medi-Cal eligible; 35.0% Healthy Families eligible).
      Twenty-eight percent of eligible children were not enrolled. Non-enrolled
      eligible children were older (median age 7) than enrolled children (median age 4)
      and more likely to be born outside the U.S. (22.2%) than enrolled children
      (4.8%). Among children ages 3-18, those not enrolled were less likely to have
      visited a doctor in the past 12 months (58% compared to 78.7%) and less likely to
      have a usual source of care (96.3% compared to 99.5%). Mothers of non-enrolled
      children were more likely than mothers of enrolled children to have less than
      seven years of education (47.8% compared to 36.4%). Families with non-enrolled
      children were more likely to report out-of-pocket medical expenses (84.1%
      compared to 53%). Families with non-enrolled children were more likely to report
      barriers to the enrollment process, such as problems providing required documents
      (39.7% compared to 15.1%), problems understanding Spanish forms (19.4% compared
      to 8.9%), and confusing paperwork (39.7% compared to 24.7%). Most mothers (75.9%)
      reported that community organizations provided very useful help with children's
      insurance enrollment. Almost half (48.6%) preferred to receive enrollment
      assistance from community organizations. Only 43.3% of mothers had heard of the
      Healthy Families program. CONCLUSIONS: To reach the majority of uninsured Latino
      children, community-based outreach and insurance application assistance are
      crucial. Most important, the process of applying for and maintaining coverage in
      Medi-Cal or Healthy Families must be simplified.

PMID- 12196619
TI  - Improving knowledge of the prostate cancer screening dilemma among African
      American men: an academic-community partnership in Washington, DC.
AB  - OBJECTIVE: Studies have shown that African American men are at greater risk than
      other men for prostate cancer in terms of both incidence and mortality. At the
      same time, the utility of screening asymptomatic men for prostate cancer remains
      controversial. The combination of high incidence and high mortality with the
      uncertain benefits of screening poses a difficult problem for African American
      men. This study was part of an ongoing project that sought to develop and
      evaluate health education materials designed to help African American men make an
      informed decision about prostate cancer screening. The project represented a
      collaboration between the Most Worshipful Prince Hall Grand Lodge of the District
      of Columbia and the Lombardi Cancer Center of Georgetown University. METHODS: The
      authors conducted eight focus groups with 44 members of the Prince Hall Masons.
      The focus groups covered men's understanding of prostate cancer screening and
      their preferences for methods of health education. RESULTS: Participants
      demonstrated a high level of awareness of the availability of prostate cancer
      screening, a low awareness of the screening controversy, and a desire for
      detailed epidemiologic information and information about the benefits and
      limitations of screening. The preferred forms of educational materials were video
      and print-based materials, which the research team has recently developed.
      CONCLUSIONS: These findings demonstrate the feasibility of developing an academic
      community collaboration with the goal of improving a health-related problem in
      the African American community. A randomized trial is underway to evaluate the
      impact of the video and print education materials.

PMID- 12196620
TI  - Is a general women's health promotion program as effective as an HIV-intensive
      prevention program in reducing HIV risk among Hispanic women?
AB  - OBJECTIVE: This study aimed to assess whether participants in an HIV-intensive
      prevention program and participants in a general women's health promotion program
      reported greater HIV risk-reduction than participants in a wait-list control
      group immediately following program participation and at three-month follow-up.
      METHODS: The authors studied 162 Hispanic women ages 18 to 35 years, most of them
      immigrants. Three-fourths of the sample (74%) reported earning less than $800 a
      month, 29% did not have a high school degree, and 90% had children. Data were
      gathered through surveys at baseline, at intervention completion, and at three
      month follow-up. Information was collected on sociodemographics, HIV risk
      factors, and risk behaviors. Crude and adjusted (for demographics and dose)
      logistic regression analyses were used to assess program effects on participants'
      risk reduction. RESULTS: Crude logistic regression analyses reveal that both
      programs resulted in increased condom use at post-test and follow-up. Only
      participants in the HIV-intensive prevention program reported increased safer sex
      negotiation at post-test and follow-up, however, and only participants in the
      women's health promotion program reported increased HIV testing at post-test.
      CONCLUSION: Both interventions increased condom use. The HIV-intensive prevention
      program appeared to be more effective in promoting safer sex negotiation, and the
      women's health promotion program appeared more effective in promoting HIV
      testing. The findings suggest that both approaches may be viable ways to package
      HIV prevention for short-term behavior change in this population.

PMID- 12196621
TI  - Low-income minority women at risk for cervical cancer: a process to improve
      adherence to follow-up recommendations.
AB  - OBJECTIVE: The Houston Department of Health and Human Services (HDHHS) has a
      centralized process for notifying and setting up follow-up appointments for women
      with abnormal Pap smears who are clients of HDHHS health centers. Faculty and a
      student from the University of Texas School of Public Health and HDHHS personnel
      jointly conducted a study to evaluate the process and performance of the system.
      METHODS: The study examined two subpopulations: women with atypical squamous
      cells of undetermined significance or low-grade squamous intraepithelial lesions
      (ASCUS/LGSIL) and women with high-grade squamous intraepithelial lesions or
      atypical glandular cells of undetermined significance (HGSIL/AGCUS). A
      retrospective study was conducted of data on women attending eight HDHHS clinics
      during the period from February 1996 through August 2000. Records of 1,216 women
      referred for evaluation of abnormal Pap smears were reviewed. Process
      effectiveness was measured by the number of successful contacts made and the
      number of appointments set up. Performance was measured by compliance with
      referral appointments. Predictors included race/ethnicity, age, co-existence of a
      sexually transmitted disease, number of prior referrals, type of patient visit,
      and health center attended. RESULTS: HDHHS staff successfully notified 95.6% of
      women with ASCUS/LGSIL and 97.9% of women with HGSIL/AGCUS. Using performance
      criteria as outcome measures, high-risk women requiring targeted interventions
      were identified. Overall, 84.2% of women scheduled appointments. Among those with
      ASCUS/LGSIL, women identified as African American were 53% less likely to accept
      an appointment and 45% less likely to show up for the appointment than those
      identified as Hispanic or "other." Age and type of patient visit appeared to be
      significantly associated with patient compliance behavior. CONCLUSION: The study
      describes the effectiveness of a centralized patient follow-up process for women
      at risk for cervical cancer.

PMID- 12196623
TI  - Culture, race and ethnicity: disparities in mental health.

PMID- 12196622
TI  - Addressing children's oral health inequalities in Northern Ireland: a research
      practice-community partnership initiative.
AB  - OBJECTIVE: Northern Ireland has a high prevalence of childhood dental caries,
      reflecting heavy consumption of cariogenic snack foods. To develop a policy to
      promote and facilitate healthier eating, researchers, practitioners, and the
      school community formed a partnership, together creating the Boost Better Breaks
      (BBB) school-based policy. The policy was developed with and supported by
      dieticians, health promotion officers, teachers, school meal advisors, and local
      suppliers of school milk. Eighty percent of primary schools and preschool groups
      within the Southern Health and Social Services Board are involved in the program,
      which permits the consumption of only milk and fruit at break time. METHODS: The
      authors assessed the effectiveness of the partnership using data from its first
      two years. RESULTS: Results of the first two years of evaluation are positive.
      Initial findings indicate that the program had a positive effect in increasing
      the mean number of sound teeth in children attending schools in areas in which
      socioeconomic conditions are poor. CONCLUSION: This initiative suggests that
      collaboration can facilitate improvement in children's dental health and that
      careful targeting of the policy to schools in poor areas has the potential to
      narrow disparities.

PMID- 12196625
TI  - Building chronic disease epidemiology capacity in a state health department: a
      partnership with a school of public health.

PMID- 12196628
TI  - The semaphorin receptor plexin-B1 signals through a direct interaction with the
      Rho-specific nucleotide exchange factor, LARG.
AB  - Semaphorins are axon guidance molecules that signal through the plexin family of
      receptors. Semaphorins also play a role in other processes such as immune
      regulation and tumorigenesis. However, the molecular signaling mechanisms
      downstream of plexin receptors have not been elucidated. Semaphorin 4D is the
      ligand for the plexin-B1 receptor and stimulation of the plexin-B1 receptor
      activates the small GTPase RhoA. Using the intracellular domain of plexin-B1 as
      an affinity ligand, two Rho-specific guanine nucleotide exchange factors,
      leukemia-associated Rho GEF (LARG; GEF, guanine nucleotide exchange factors) and
      PSD-95/Dlg/ZO-1 homology (PDZ)-RhoGEF, were isolated from mouse brain as plexin
      B1-specific interacting proteins. LARG and PDZ-RhoGEF contain several functional
      domains, including a PDZ domain. Biochemical characterizations showed that the
      PDZ domain of LARG is directly involved in the interaction with the carboxy
      terminal sequence of plexin-B1. Mutation of either the PDZ domain in LARG or the
      PDZ binding site in plexin-B1 eliminates the interaction. The interaction between
      plexin-B1 and LARG is specific for the PDZ domain of LARG and LARG does not
      interact with plexin-A1. A LARG-interaction defective mutant of the plexin-B1
      receptor was created and was unable to stimulate RhoA activation. The data in
      this report suggest that LARG plays a critical role in plexin-B1 signaling to
      stimulate Rho activation and cytoskeletal reorganization.

PMID- 12196629
TI  - Cytochrome c folding pathway: kinetic native-state hydrogen exchange.
AB  - Native-state hydrogen exchange experiments under EX1 conditions can distinguish
      partially unfolded intermediates by their formation rates and identify the amide
      hydrogens exposed and protected in each. Results obtained define a cytochrome c
      intermediate seen only poorly before and place it early on the major unfolding
      pathway. Four distinct unfolding steps are found to be kinetically ordered in the
      same pathway sequence inferred before.

PMID- 12196630
TI  - Regulation of V(D)J recombination: a dominant role for promoter positioning in
      gene segment accessibility.
AB  - Antigen receptor gene assembly is regulated by transcriptional promoters and
      enhancers, which control the accessibility of gene segments to a lymphocyte
      specific V(D)J recombinase. However, it remained unclear whether accessibility
      depends on the process of transcription itself or chromatin modifications that
      accompany transcription. By using T cell receptor beta substrates that integrate
      stably into nuclear chromatin, we show that promoter location, rather than germ
      line transcription or histone acetylation, is a primary determinant of
      recombination efficiency. These spatial constraints on promoter positioning may
      reflect an RNA polymerase-independent mechanism to target adjacent gene segments
      for chromatin remodeling events that facilitate rearrangement.

PMID- 12196631
TI  - Mechanism by which 2,2,2-trifluoroethanol/water mixtures stabilize secondary
      structure formation in peptides: a molecular dynamics study.
AB  - Molecular dynamics simulation techniques have been used to investigate the effect
      of 2,2,2-trifluoroethanol (TFE) as a cosolvent on the stability of three
      different secondary structure-forming peptides: the alpha-helix from Melittin,
      the three-stranded beta-sheet peptide Betanova, and the beta-hairpin 41-56 from
      the B1 domain of protein G. The peptides were studied in pure water and 30%
      (vol/vol) TFE/water mixtures at 300 K. The simulations suggest that the
      stabilizing effect of TFE is induced by the preferential aggregation of TFE
      molecules around the peptides. This coating displaces water, thereby removing
      alternative hydrogen-bonding partners and providing a low dielectric environment
      that favors the formation of intrapeptide hydrogen bonds. Because TFE interacts
      only weakly with nonpolar residues, hydrophobic interactions within the peptides
      are not disrupted. As a consequence, TFE promotes stability rather than inducing
      denaturation.

PMID- 12196632
TI  - Heritable chromatin structure: mapping "memory" in histones H3 and H4.
AB  - Telomeric position effect in Saccharomyces cerevisiae is a chromatin-mediated
      phenomenon in which telomere proximal genes are repressed (silenced) in a
      heritable, but reversible, fashion. Once a transcriptional state (active or
      silenced) is established, however, there is a strong tendency for that state to
      be propagated. Twenty-five years ago, H. Weintraub and colleagues suggested that
      such heritability could be mediated by posttranslational modification of
      chromatin [Weintraub, H., Flint, S. J., Leffak, I. M., Groudine, M. & Grainger,
      R. M. (1977) Cold Spring Harbor Symp. Quant. Biol. 42, 401-407]. To identify
      potential sites within the chromatin that might act as sources of "memory" for
      the heritable transmission, we performed a genetic screen to isolate mutant
      alleles of the histones H3 and H4 genes that would "lock" telomeric marker genes
      into a silenced state. We identified mutations in the NH(2)-terminal tail and
      core of both histones; most of the amino acid changes mapped adjacent to lysines
      that are known sites of acetylation or methylation. We developed a method using
      MS to quantify the level of acetylation at each lysine within the histone H4
      NH(2)-terminal tail in these mutants. We discovered that each of these mutants
      had a dramatic reduction in the level of acetylation at lysine 12 within the
      histone H4 tail. We propose that this lysine serves as a "memory mark" for
      propagating the expression state of a telomeric gene: when it is unacetylated,
      silent chromatin will be inherited; when it is acetylated an active state will be
      inherited.

PMID- 12196633
TI  - Transitive functional annotation by shortest-path analysis of gene expression
      data.
AB  - Current methods for the functional analysis of microarray gene expression data
      make the implicit assumption that genes with similar expression profiles have
      similar functions in cells. However, among genes involved in the same biological
      pathway, not all gene pairs show high expression similarity. Here, we propose
      that transitive expression similarity among genes can be used as an important
      attribute to link genes of the same biological pathway. Based on large-scale
      yeast microarray expression data, we use the shortest-path analysis to identify
      transitive genes between two given genes from the same biological process. We
      find that not only functionally related genes with correlated expression profiles
      are identified but also those without. In the latter case, we compare our method
      to hierarchical clustering, and show that our method can reveal functional
      relationships among genes in a more precise manner. Finally, we show that our
      method can be used to reliably predict the function of unknown genes from known
      genes lying on the same shortest path. We assigned functions for 146 yeast genes
      that are considered as unknown by the Saccharomyces Genome Database and by the
      Yeast Proteome Database. These genes constitute around 5% of the unknown yeast
      ORFome.

PMID- 12196634
TI  - Cloning the vaccinia virus genome as a bacterial artificial chromosome in
      Escherichia coli and recovery of infectious virus in mammalian cells.
AB  - The ability to manipulate the vaccinia virus (VAC) genome, as a plasmid in
      bacteria, would greatly facilitate genetic studies and provide a powerful
      alternative method of making recombinant viruses. VAC, like other poxviruses, has
      a linear, double-stranded DNA genome with covalently closed hairpin ends that are
      resolved from transient head-to-head and tail-to-tail concatemers during
      replication in the cytoplasm of infected cells. Our strategy to construct a
      nearly 200,000-bp VAC-bacterial artificial chromosome (BAC) was based on
      circularization of head-to-tail concatemers of VAC DNA. Cells were infected with
      a recombinant VAC containing inserted sequences for plasmid replication and
      maintenance in Escherichia coli; DNA concatemer resolution was inhibited leading
      to formation and accumulation of head-to-tail concatemers, in addition to the
      usual head-to-head and tail-to-tail forms; the concatemers were circularized by
      homologous or Cre-loxP-mediated recombination; and E. coli were transformed with
      DNA from the infected cell lysates. Stable plasmids containing the entire VAC
      genome, with an intact concatemer junction sequence, were identified. Rescue of
      infectious VAC was consistently achieved by transfecting the VAC-BAC plasmids
      into mammalian cells that were infected with a helper nonreplicating fowlpox
      virus.

PMID- 12196636
TI  - Brain death.

PMID- 12196635
TI  - The antiangiogenic activity of cleaved high molecular weight kininogen is
      mediated through binding to endothelial cell tropomyosin.
AB  - Conformationally altered proteins and protein fragments derived from the
      extracellular matrix and hemostatic system may function as naturally occurring
      angiogenesis inhibitors. One example of such a protein is cleaved high molecular
      weight kininogen (HKa). HKa inhibits angiogenesis by inducing apoptosis of
      proliferating endothelial cells, effects mediated largely by HKa domain 5.
      However, the mechanisms underlying the antiangiogenic activity of HKa have not
      been characterized, and its binding site on proliferating endothelial cells has
      not been defined. Here, we report that the induction of endothelial cell
      apoptosis by HKa, as well as the antiangiogenic activity of HKa in the chick
      chorioallantoic membrane, was inhibited completely by antitropomyosin monoclonal
      antibody TM-311. TM-311 also blocked the high-affinity Zn2+-dependent binding of
      HKa to both purified tropomyosin and proliferating endothelial cells. Confocal
      microscopic analysis of endothelial cells stained with monoclonal antibody TM
      311, as well as biotin labeling of cell surface proteins on intact endothelial
      cells, revealed that tropomyosin exposure was enhanced on the surface of
      proliferating cells. These studies demonstrate that the antiangiogenic effects of
      HKa depend on high-affinity binding to endothelial cell tropomyosin.

PMID- 12196637
TI  - Resuscitation of sudden cardiac death: a mandate for neurology and emergency
      medicine.

PMID- 12196638
TI  - Using bone marrow stromal cells for treatment of stroke.

PMID- 12196639
TI  - "Out, damned spot! out, I say!...": issues related to prion decontamination.

PMID- 12196640
TI  - Practice parameter: evaluation of children and adolescents with recurrent
      headaches: report of the Quality Standards Subcommittee of the American Academy
      of Neurology and the Practice Committee of the Child Neurology Society.
AB  - OBJECTIVE: The Quality Standards Subcommittee of the American Academy of
      Neurology and the Practice Committee of the Child Neurology Society develop
      practice parameters as strategies for patient management based on analysis of
      evidence. For this parameter, the authors reviewed available evidence on the
      evaluation of the child with recurrent headaches and made recommendations based
      on this evidence. METHODS: Relevant literature was reviewed, abstracted, and
      classified. Recommendations were based on a four-tiered scheme of evidence
      classification. RESULTS: There is inadequate documentation in the literature to
      support any recommendation as to the appropriateness of routine laboratory
      studies or performance of lumbar puncture. EEG is not recommended in the routine
      evaluation, as it is unlikely to define or determine an etiology or distinguish
      migraine from other types of headaches. In those children undergoing evaluation
      for recurrent headache found to have a paroxysmal EEG, the risk for future
      seizures is negligible; therefore, further investigation for epilepsy or
      treatments aimed at preventing future seizures is not indicated. Obtaining a
      neuroimaging study on a routine basis is not indicated in children with recurrent
      headaches and a normal neurologic examination. Neuroimaging should be considered
      in children with an abnormal neurologic examination or other physical findings
      that suggest CNS disease. Variables that predicted the presence of a space
      occupying lesion included 1) headache of less than 1-month duration; 2) absence
      of family history of migraine; 3) abnormal neurologic findings on examination; 4)
      gait abnormalities; and 5) occurrence of seizures. CONCLUSIONS: Recurrent
      headaches occur commonly in children and are diagnosed on a clinical basis rather
      than by any testing. The routine use of any diagnostic studies is not indicated
      when the clinical history has no associated risk factors and the child's
      examination is normal.

PMID- 12196641
TI  - Randomized clinical trial of magnesium, diazepam, or both after out-of-hospital
      cardiac arrest.
AB  - OBJECTIVE: To evaluate the feasibility, safety, and efficacy of interventions
      aimed at improving neurologic outcome after cardiac arrest. METHODS: The authors
      conducted a double-blind, placebo-controlled, randomized clinical trial with
      factorial design to see if magnesium, diazepam, or both, when given immediately
      following resuscitation from out-of-hospital cardiac arrest, would increase the
      proportion of patients awakening, defined as following commands or having
      comprehensible speech. If the patient regained a systolic blood pressure of at
      least 90 mm Hg and had not awakened, paramedics injected IV two syringes stored
      in a sealed kit. The first always contained either 2 g magnesium sulfate (M) or
      placebo (P); the second contained either 10 mg diazepam (D) or P. Awakening at
      any time by 3 months was determined by record review, and independence at 3
      months was determined by telephone calls. Over 30 months, 300 patients were
      randomized in balanced blocks of 4, 75 each to MD, MP, PD, or PP. The study was
      conducted under waiver of consent. RESULTS: Despite the design, the four
      treatment groups differed on baseline variables collected before randomization.
      Percent awake by 3 months for each group were: MD, 29.3%; MP, 46.7%; PD, 30.7%;
      PP, 37.3%. Percent independent at 3 months were: MD, 17.3%; MP, 34.7%; PD, 17.3%;
      PP, 25.3%. Significant interactions were lacking. After adjusting for baseline
      imbalances, none of these differences was significant, and no adverse effects
      were identified. CONCLUSIONS: Neither magnesium nor diazepam significantly
      improved neurologic outcome from cardiac arrest.

PMID- 12196642
TI  - Human marrow stromal cell therapy for stroke in rat: neurotrophins and functional
      recovery.
AB  - OBJECTIVE: To test the effect of i.v.-injected human bone marrow stromal cells
      (hMSC) on neurologic functional deficits after stroke in rats. METHODS: Rats were
      subjected to transient middle cerebral artery occlusion and IV injected with 3 x
      10(6) hMSC 1 day after stroke. Functional outcome was measured before and 1, 7,
      and 14 days after stroke. Mixed lymphocyte reaction and the development of
      cytotoxic T lymphocytes measured the immune rejection of hMSC. A monoclonal
      antibody specific to human cellular nuclei (mAb1281) was used to identify hMSC
      and to measure neural phenotype. ELISA analyzed neurotrophin levels in cerebral
      tissue from hMSC-treated or nontreated rats. Bromodeoxyuridine injections were
      used to identify newly formed cells. RESULTS: Significant recovery of function
      was found in rats treated with hMSC at 14 days compared with control rats with
      ischemia. Few (1 to 5%) hMSC expressed proteins phenotypic of brain parenchymal
      cells. Brain-derived neurotrophic factor and nerve growth factor significantly
      increased, and apoptotic cells significantly decreased in the ischemic boundary
      zone; significantly more bromodeoxyuridine-reactive cells were detected in the
      subventricular zone of the ischemic hemisphere of rats treated with hMSC. hMSC
      induced proliferation of lymphocytes without the induction of cytotoxic T
      lymphocytes. CONCLUSION: Neurologic benefit resulting from hMSC treatment of
      stroke in rats may derive from the increase of growth factors in the ischemic
      tissue, the reduction of apoptosis in the penumbral zone of the lesion, and the
      proliferation of endogenous cells in the subventricular zone.

PMID- 12196643
TI  - Risk factors for subclinical carotid atherosclerosis in healthy men.
AB  - BACKGROUND AND OBJECTIVE: Ultrasound-detected carotid artery intima-media
      thickness (IMT) is regarded as a valid index of atherosclerosis. Cross-sectional
      studies have been helpful in establishing determinants of IMT, but the long-term
      relationship between cardiovascular risk factors and subclinical atherosclerosis
      in a low-risk population has not been thoroughly evaluated. METHODS: A cohort of
      483 military aviators, officially considered as fit for flying and therefore
      normotensive, was included in the study. All subjects underwent baseline
      examination with measurement of cardiovascular risk factors (body mass index,
      blood pressure, physical working capacity, cigarette smoking, and levels of
      cholesterol, high-density lipoprotein cholesterol, triglycerides, and gamma
      glutamyltransferase) and carotid ultrasonography at the end point after 10 years
      of follow-up. RESULTS: Age, cigarette smoking, and blood pressure were
      independent long-term predictors of IMT. After adjustment for age, cigarettes
      smoked daily at baseline, categorized in units of five cigarettes each
      (regression coefficient in mm, 0.057 [95% CI: 0.029 to 0.085]; p < 0.0001), and
      systolic blood pressure (regression coefficient in mm, 0.007 [95% CI: 0.003 to
      0.010], p < 0.0001) were the only predictors of IMT. Physical working capacity
      was not associated with IMT. CONCLUSION: Even in normotensive individuals,
      systolic blood pressure is a strong predictor of early carotid atherosclerosis.

PMID- 12196644
TI  - Homocysteine, MTHFR 677C-->T polymorphism, and risk of ischemic stroke: results
      of a meta-analysis.
AB  - BACKGROUND: Data are conflicting concerning risk for ischemic stroke associated
      with hyperhomocyst(e)inemia (hyper-Hcy) and a common polymorphism in the gene
      encoding 5,10-methylenetetrahydrofolate reductase (MTHFR 677C-->T), which
      predisposes to hyper-Hcy in vivo. METHODS: Search of MEDLINE, Science Citation
      Index, and abstracts of conference proceedings revealed relevant articles.
      Exposure was defined as follows: 1) prevalence of hyper-Hcy; 2) absolute
      difference in the mean Hcy concentration between subjects with and without
      ischemic stroke; and 3) the MTHFR TT genotype frequency. Outcome was defined as
      ischemic stroke with or without neuroimaging. Inclusion criteria were
      retrospective and prospective studies with reported odds ratios (OR) or hazard
      ratios (HR) or arithmetic mean Hcy levels. Exclusion criteria were absence of OR
      or HR, outcome defined as carotid atherosclerosis or intima-media thickening,
      stroke in patients younger than 18 years old, and studies in languages other than
      English. Statistical analyses for between-study heterogeneity and pooled risk
      estimates were performed using Stata software (Stata Corporation, College
      Station, TX). RESULTS: Among 16 studies (1,487 stroke and 2,554 nonstroke cases),
      the pooled mean Hcy level in patients with ischemic stoke was 2.32 micromol/L
      (95% CI, 1.6 to 3.04; p < 0.001) greater than that in those without ischemic
      stroke. Among 14 included studies (1,769 stroke and 7,400 nonstroke cases), the
      pooled OR estimate of ischemic stroke associated with hyper-Hcy was 1.79 (95% CI,
      1.61 to 2.0; p < 0.001). Among 19 included studies (2,788 stroke and 3,962
      nonstroke cases), the OR associated with the TT genotype was 1.23 (95% CI, 0.96
      to 1.58; p = 0.1). CONCLUSION: These data support an association between mild-to
      moderate hyper-Hcy and ischemic stoke. The MTHFR TT genotype may have a small
      influence in determining susceptibility to ischemic stoke.

PMID- 12196645
TI  - Mortality in patients with dementia after ischemic stroke.
AB  - OBJECTIVE: Although dementia is typically considered to be a consequence of a
      variety of neurologic diseases, it can also serve as a risk factor for other
      adverse outcomes. The authors investigated dementia as a predictor of long-term
      survival among patients with ischemic stroke. METHODS: Neurologic,
      neuropsychological, and functional assessments were administered to 453 patients
      (mean age +/- SD, 72.0 +/- 8.3 years) 3 months after ischemic stroke. The authors
      diagnosed dementia in 119 (26.3%) of the patients using modified Diagnostic and
      Statistical Manual of Mental Disorders, Revised 3rd Edition, criteria requiring
      deficits in memory and two or more additional cognitive domains as well as
      functional impairment. Dementia as a predictor of long-term survival during up to
      10 years of follow-up was then investigated. RESULTS: The mortality rate was
      15.90 deaths per 100 person-years among patients with dementia and 5.37 deaths
      per 100 person-years among nondemented patients. A Cox proportional hazards
      analysis found that the relative risk (RR) of death was increased in association
      with dementia (RR = 2.4; 95% CI = 1.6 to 3.4), adjusting for the following: a
      major hemispheral stroke syndrome (RR = 1.4); a middle cerebral artery territory
      index stroke (RR = 1.7); a Stroke Severity Scale score of > or = 4, representing
      more severe stroke (RR = 1.8); atrial fibrillation (RR = 1.8); congestive heart
      failure (RR = 2.2); recurrent stroke occurring during follow-up (RR = 3.9); and
      demographic variables. The risk of death increased in association with the
      severity of dementia, but it did not differ by dementia subtype. CONCLUSIONS:
      Dementia is a significant independent risk factor for reduced survival after
      ischemic stroke, adjusting for other recognized predictors of mortality. The
      authors hypothesize that patients with dementia are at an elevated risk of
      mortality because of their increased burden of cerebrovascular disease, a
      tendency toward undertreatment for stroke prophylaxis among clinicians, or
      patient noncompliance with treatment regimens.

PMID- 12196646
TI  - Sporadic Creutzfeldt-Jakob disease and surgery: a case-control study using
      community controls.
AB  - BACKGROUND: The cause of sporadic Creutzfeldt-Jakob disease (CJD) is unknown.
      Previous studies found a link with a history of surgery but had methodologic
      problems. OBJECTIVE: To help elucidate medical and associated risk factors for
      sporadic CJD as part of the 1993 to 1995 European Union collaborative studies of
      CJD. METHODS: Medical and associated risk factors from 326 patients with sporadic
      CJD, taken from population-based studies performed between 1993 and 1995 in
      France, Germany, the Netherlands, and the UK, were compared with 326 community
      controls recruited by telephone in 2000. RESULTS: A history of surgery was
      significantly associated with the risk of sporadic CJD (odds ratio [OR]: 1.8; 95%
      CI: 1.2 to 2.6), which was not dependent on the number of surgical procedures,
      and was stronger in females (OR: 2.5; 95% CI: 1.5 to 4.0). Gynecologic (OR: 1.5;
      95% CI: 1.0 to 2.3) and "other" operations (any operation other than neurologic,
      eye, ear, gallbladder, gastrointestinal, and gynecologic operations,
      tonsillectomy, and appendectomy) (OR: 1.5; 95% CI: 1.1 to 2.1) were associated
      with risk of CJD. Tonsillectomy (OR: 0.3; 95% CI: 0.2 to 0.5) and appendectomy
      (OR: 0.6; 95% CI: 0.4 to 0.8) were observed less frequently in cases. An
      increased risk was also found with a history of ear piercing in females (OR: 1.6;
      95% CI: 1.1 to 2.5) and psychiatric visit(s) (OR: 2.6; 95% CI: 1.5 to 4.3).
      CONCLUSIONS: These results support the hypothesis that cases of sporadic CJD may
      result from hitherto unrecognized surgical contamination events. However, because
      of the limits of the study design, the rarity of the disease, and the potential
      for bias, the results should be interpreted with caution.

PMID- 12196647
TI  - Evidence for additional genetic risk indicators of relapse-onset MS within the
      HLA region.
AB  - BACKGROUND: Human leukocyte antigen (HLA)-DR2 carriership is associated with an
      increased risk for MS. Genome searches using microsatellite markers have
      consistently shown that additional genetic factors contribute to susceptibility
      for MS. OBJECTIVE: To identify loci within the HLA region that predispose to
      relapse-onset MS independently of HLA-DR2. METHOD: A case-control study involving
      159 patients with definite relapse-onset MS and 273 control subjects was
      conducted. Six highly polymorphic microsatellite markers encoded within the HLA-C
      to DR region, that is, D6S1014, D6S273, TNFa, MIB, C1_2_5, and C1_3_2, three
      single-nucleotide tumor necrosis factor (TNF) promoter gene polymorphisms at
      positions -238, -308, and -376, and HLA-DR2 carriership were typed. RESULTS:
      These data confirmed the well-known association between the HLA-DR2 haplotype and
      relapse-onset MS, yielding an odds ratio (OR) of 3.6 (95% CI: 2.4 to 5.4; p <
      0.0001). Multivariate analyses revealed that C1_3_2*354 was also associated with
      an increased risk for developing relapse-onset MS independently of HLA-DR2 (OR:
      2.0; 95% CI: 1.2 to 3.1; p = 0.004). This allele is encoded within an ancestral
      haplotype that is highly linked to HLA-DR3. The joint effect of this ancestral
      haplotype and HLA-DR2 resulted in an OR of 8.7 (95% CI: 2.7 to 29; p < 0.0001) to
      develop relapse-onset MS. In addition, a protective risk factor was found:
      carriers of TNFa*107 had a 0.5-fold lower risk to develop relapse-onset MS (95%
      CI: 0.3 to 0.9; p = 0.026). CONCLUSION: Within the HLA region, other loci besides
      HLA-DR2 haplotype modulate susceptibility for relapse-onset MS.

PMID- 12196648
TI  - Intrathecal IgM synthesis predicts the onset of new relapses and a worse disease
      course in MS.
AB  - BACKGROUND: The authors have recently described that intrathecal IgM synthesis
      (ITMS) correlates with a higher disability in patients with clinically definite
      MS (CDMS). OBJECTIVE: To follow-up a group of patients with MS in the initial
      stages of the disease to evaluate if the presence of ITMS correlates with a worse
      evolution. METHODS: Oligoclonal IgM bands were performed in 22 patients with MS
      with a mean of 1.14 months of evolution. Patients were followed for a period
      ranging from 6 to 36 months (mean, 21.4 months). During follow-up, time to
      conversion to CDMS, number of relapses, and changes in Expanded Disability Status
      Scale (EDSS) score were evaluated. RESULTS: Patients were divided into two groups
      according to the presence (Group 1, 10 patients) or absence (Group 2, 12
      patients) of ITMS. No clinical differences were observed between the groups at
      inclusion in the study. During the follow-up, the probability of conversion to
      CDMS was greater in Group 1 (90% of the patients had converted to CDMS after 8
      months of follow-up) than in Group 2 (51% of patients had converted to CDMS after
      36 months of follow-up) (p = 0.0001). Patients from Group 1 had more relapses
      (mean, 2.0) than those from Group 2 (mean, 0.58) (p = 0.02). At the end of the
      study, patients from Group 1 had higher EDSS scores (mean, 1.70) than those from
      Group 2 (mean, 0.79) (p = 0.02). CONCLUSION: The presence of oligoclonal IgM
      bands in CSF can be a prognostic marker in the early phases of MS.

PMID- 12196649
TI  - Transcranial magnetic stimulation for the treatment of seizures: a controlled
      study.
AB  - OBJECTIVE: To perform a controlled trial of transcranial magnetic stimulation
      (TMS). METHODS: Twenty-four patients with localization-related epilepsy were
      randomized to blinded active or placebo stimulation. Weekly seizure frequency was
      compared for 8 weeks before and after 1 week of 1-Hz TMS for 15 minutes twice
      daily. RESULTS: When the 8-week baseline and post-stimulation periods were
      compared, active patients had a mean seizure frequency reduction of 0.045 +/-
      0.13 and sham-stimulated control subjects -0.004 +/- 0.20. Over 2 weeks, actively
      treated patients had a mean reduction in weekly seizure frequency of 0.16 +/-
      0.18 and sham-stimulated control subjects 0.01 +/- 0.24. Neither difference was
      significant. CONCLUSION: The effect of TMS on seizure frequency was mild and
      short lived.

PMID- 12196650
TI  - Sustained cholinesterase inhibition in AD patients receiving rivastigmine for 12
      months.
AB  - OBJECTIVE: To study the long-term dual inhibitory effects of rivastigmine on
      acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) in patients with
      AD. METHODS: Eleven patients with mild AD received rivastigmine for 12 months.
      Cholinesterase (ChE) activities in the CSF and plasma were assessed
      colorimetrically. Immunoblot analysis was used to evaluate AChE isoforms.
      Neuropsychiatric tests were performed throughout the study. RESULTS: At 12
      months, the mean dose of rivastigmine was 8.6 mg/d and specific activities of ChE
      in the CSF were lower than baseline values (by 36% for AChE and 45% for BuChE),
      correlating with parallel reductions in the plasma (27% for AChE and 33% for
      BuChE). The reduction of specific activities in the CSF, but not in the plasma,
      appeared to be dependent on the dose and duration of treatment. Scores of some of
      the neuropsychological tests associated with memory and attention were correlated
      with both plasma and CSF AChE and BuChE inhibition for up to 6 months. Immunoblot
      analysis revealed up-regulation of the "read-through" AChE isoform (AChE-R),
      whereas levels of the synaptic isoform were unchanged. CONCLUSIONS: Rivastigmine
      causes persistent inhibition of AChE and BuChE in CSF as well as plasma. The
      persistent CSF inhibition contrasts with earlier findings after long-term
      treatment by the reversible ChE inhibitor tacrine, which demonstrated increased
      AChE activity in the CSF but not in the blood. Rivastigmine's effects on the
      preferential up-regulation of the AChE-R isoform may have a favorable effect on
      disease stabilization.

PMID- 12196651
TI  - Primary care expenditures before the onset of Alzheimer's disease.
AB  - OBJECTIVE: To investigate primary care expenditures in the period before
      diagnosis of AD. METHODS: In a population-based sample of Medicare enrollees in
      New York City, person-level 1996 Medicare claims, summed over primary care
      encounters, were examined for people who developed AD in 1997 to 1998 and those
      who did not. RESULTS: People who developed AD were more likely to use Medicare
      outpatient and ambulatory care 1 to 2 years before diagnosis. Compared with
      respondents who did not develop AD, the excess cost for men was $1,167 (85%
      higher) and for women $239 (26% higher). Among elderly people > or = 75 years in
      the United States, the prodromal period of AD was associated with an excess
      Medicare-based primary care cost of $128.5 to $194.7 million. CONCLUSION: In
      addition to huge costs associated with AD after diagnosis, prediagnosis costs are
      an unrecognized source of expenditures related to the disease.

PMID- 12196653
TI  - Clinical and genetic heterogeneity in benign hereditary chorea.
AB  - BACKGROUND: Benign hereditary chorea (BHC) is an autosomal dominant disorder that
      can be distinguished from Huntington disease by its early onset, stable or only
      slightly progressive course, and absence of mental deterioration. The variation
      in clinical features is such that its very existence has been doubted. The
      authors recently described the localization of a gene responsible for BHC on
      chromosome 14q in a large Dutch family. OBJECTIVE: To report results of extensive
      clinical and linkage analyses for this Dutch family and six other families with
      BHC. RESULTS: Three of the seven families had linkage to a region on chromosome
      14q13.1-q21.1. HOMOG analysis showed odds of 10 x 10(11) in favor of locus
      heterogeneity. Haplotype analyses for the linked families resulted in a reduction
      of the critical interval for the BHC gene to 8.4 cM between marker D14S49 and
      marker D14S278. Clinically, these three families had a homogeneous picture with
      early-onset chorea, sometimes accompanied by slight ataxia in walking, but
      without dystonia, myoclonic jerks, or dysarthria. The severity of the choreatic
      movements tended to abate in adolescence or early adulthood. In the unlinked
      families, symptoms and signs were more heterogeneous as to age at onset and the
      occurrence of myoclonic jerks or dystonia. CONCLUSIONS: BHC is a clinically and
      genetically heterogeneous disorder, with one well-defined clinical syndrome
      mapping to chromosome 14q.

PMID- 12196654
TI  - REM sleep behavior disorder and REM sleep without atonia in Parkinson's disease.
AB  - OBJECTIVE: To determine the frequency of REM sleep behavior disorder (RBD) among
      patients with PD using both history and polysomnography (PSG) recordings and to
      further study REM sleep muscle atonia in PD. BACKGROUND: The reported occurrence
      of RBD in PD varies from 15 to 47%. However, no study has estimated the frequency
      of RBD using PSG recordings or analyzed in detail the characteristics of REM
      sleep muscle atonia in a large group of unselected patients with PD. METHODS:
      Consecutive patients with PD (n = 33) and healthy control subjects (n = 16) were
      studied. Each subject underwent a structured clinical interview and PSG
      recording. REM sleep was scored using a method that allows the scoring of REM
      sleep without atonia. RESULTS: One third of patients with PD met the diagnostic
      criteria of RBD based on PSG recordings. Only one half of these cases would have
      been detected by history. Nineteen (58%) of 33 patients with PD but only 1 of 16
      control subjects had REM sleep without atonia. Of these 19 patients with PD, 8
      (42%) did not present with behavioral manifestations of RBD, and their cases may
      represent preclinical forms of RBD associated with PD. Moreover, the percentage
      of time spent with muscle atonia during REM sleep was lower among patients with
      PD than among healthy control subjects (60.1% vs 93.2%; p = 0.003). CONCLUSIONS:
      RBD and REM sleep without atonia are frequent in PD as shown by PSG recordings.

PMID- 12196655
TI  - Early-onset ataxia with ocular motor apraxia and hypoalbuminemia: the aprataxin
      gene mutations.
AB  - BACKGROUND: Early-onset ataxia with hypoalbuminemia is regarded as a variant form
      of Friedreich ataxia in Japan. Early-onset ataxia with hypoalbuminemia and ataxia
      with ocular motor apraxia have been considered as the same clinical entity
      because of the recent identification of a common mutation in the aprataxin gene.
      A new clinical entity named early-onset ataxia with ocular motor apraxia and
      hypoalbuminemia (EAOH) has been proposed to explain these two diseases.
      OBJECTIVE: To disclose the clinical features of EAOH and to identify the
      mutations in the aprataxin gene in six patients in four Japanese families with
      EAOH. METHODS: The clinical features, laboratory findings, sural nerve biopsy
      results, and brain MRI or CT findings for these patients were evaluated, and
      molecular analysis was performed, which involved sequencing of the aprataxin gene
      directly or use of the subcloning method. RESULTS: Cerebellar ataxia and
      peripheral neuropathy were noted in all six patients. Ocular motor apraxia was
      observed in five patients; two of these patients had obvious head thrust.
      Choreiform movements of the limbs and mental deterioration were observed in five
      patients. Although foot deformity was noted in five patients, kyphoscoliosis was
      noted only in one patient. In all patients, hypoalbuminemia and
      hypercholesterolemia were evident, and brain MRI or CT showed marked cerebellar
      atrophy. Nerve biopsy revealed depletion of large myelinated fibers in three of
      the five patients examined. Molecular analysis of the aprataxin gene revealed an
      insertion mutation (insT at nt167) and two missense mutations (A-to-G transition
      at nt80 and C-to-T transition at nt95, the former being novel). CONCLUSION: We
      found clinical heterogeneity in the patients with EAOH in this study. With the
      disease course, the choreiform movements tended to reduce in degree, and
      hypoalbuminemia became evident. Molecular analysis identified one insertion and
      two missense mutations including a novel missense one, which was located at a
      highly conserved amino acid residue in the aprataxin gene product.

PMID- 12196656
TI  - Narrowing in on the causative defect of an intriguing X-linked myopathy with
      excessive autophagy.
AB  - BACKGROUND: X-Linked myopathy with excessive autophagy (XMEA) is a childhood
      onset slowly progressive disease of skeletal muscle with no cardiac, nervous
      system, or other organ involvement. Pathology is distinctive: membrane-bound
      autophagic vacuoles, multifold reduplication of the basement membrane, and
      intense deposition of membrane attack complex and calcium at the myofiber
      surface. XMEA has been linked to the most telomeric 10.5 cM of Xq28. The authors
      now report identification of new families, refinement of the locus, mapping of
      genes to the region, and screening of candidate genes for mutations. METHODS AND
      RESULTS: Seven new families were ascertained, including an American family with
      XMEA. Using 11 new microsatellite genetic markers, the authors fine-mapped a
      recombination in this family and a common ancestral haplotype in two French
      families, which localized the gene in a 4.37-Mb region. Sequence data were
      assembled from public and private databases and a near-continuous sequence
      derived for the entire region. With this sequence, a gene map of 82 genes and 28
      expressed sequence tag clusters was constructed; to date, 12 candidate genes have
      been screened for mutations. CONCLUSIONS: This study doubles the number of
      reported families with XMEA and more firmly establishes its distinctive
      clinicopathologic features. It also advances the search for the XMEA causative
      defect by reducing the disease locus to approximately half its previous size,
      assembling an almost complete sequence of the refined region, identifying all
      known genes in this sequence, and excluding the presence of mutations in 10% of
      these genes.

PMID- 12196657
TI  - Acute confusional state following liver transplantation for alcoholic liver
      disease.
AB  - BACKGROUND: Neurologic complications occur in 10% to 20% of patients after liver
      transplantation. OBJECTIVE: To assess postoperative neurologic complications in
      relation to increased use of liver transplantation for alcoholic liver disease.
      METHODS: Neurologic complications in 40 patients who received liver
      transplantation for alcoholic liver disease were compared with those in 47
      patients who had transplantation for hepatitis C. All patients were older than 50
      years and received transplants between 1990 and 2000. RESULTS: Acute confusion
      for 3 or more days occurred in 48% of the patients with alcoholic liver disease
      but in only 6% of those with hepatitis C (p < 0.0001). Neurotoxicity related to
      calcineurin inhibitor medication occurred in 7% of the alcohol group and 15% of
      the hepatitis C group (p = 0.33). Critical illness polyneuropathy and myopathy
      were noted in 10% of the patients with alcoholism and 2% of the patients with
      hepatitis C (p = 0.18). A shorter duration of sobriety within the alcohol group
      was associated with acute confusional state (p = 0.02). An increased preoperative
      level of ammonia in serum was a risk factor for post-transplantation acute
      confusional state (p = 0.001). Patients with postoperative acute confusional
      state had a longer hospital stay (p = 0.0002). CONCLUSIONS: An acute confusional
      state occurred in more than half the patients with transplantation for alcoholic
      liver disease. Increased pretransplantation serum level of ammonia and shorter
      duration of sobriety were risk factors in these patients.

PMID- 12196658
TI  - Parry-Romberg syndrome with migraine and intracranial aneurysm.
AB  - Parry-Romberg syndrome or progressive facial hemiatrophy (PFH) is a rare disease
      of unknown etiology characterized by atrophy of the skin and subcutaneous tissue
      on one side of the face. The authors present the case of a 32-year-old woman with
      PFH who had migraine and an intracranial aneurysm. The findings support the
      hypothesis that the disease could be related to a neural crest migration
      disorder, from which both fronto-nasal mass and cranial vessels take origin.

PMID- 12196659
TI  - Pilot trial of albuterol in spinal muscular atrophy.
AB  - The aim of this pilot study was to evaluate the effect of albuterol in children
      with spinal muscular atrophy (SMA). Thirteen patients (five with SMA II and eight
      with SMA III) were given oral albuterol for 6 months. There was a significant
      increase in myometry, forced vital capacity, and lean body mass between the
      baseline and the 6-month assessments (p < 0.05). Albuterol may have a beneficial
      effect in patients with SMA without causing any significant adverse effects.
      Larger randomized, placebo-controlled trials are needed to confirm this
      observation.

PMID- 12196660
TI  - Comparison of sensory testing on different toe surfaces: implications for
      neuropathy screening.
AB  - Successful screening for neuropathy in patients with diabetes is available using
      the 10 g Semmes-Weinstein monofilament (Mid-Delta Health Systems, Inc., Belzoni,
      MS) (touch/pressure sensation) and the Neurothesiometer (Horwell Scientific,
      London, UK; vibration perception threshold). In healthy volunteers and patients
      with a broad range of diabetic sensorimotor neuropathy, we show that the
      predictive value of either test for diabetic sensorimotor neuropathy depends on
      the toe surface tested. These results establish the importance of standardized
      screening methods for diabetic sensorimotor neuropathy in the clinic and in
      clinical research trials.

PMID- 12196661
TI  - Mutations of the slow muscle alpha-tropomyosin gene, TPM3, are a rare cause of
      nemaline myopathy.
AB  - The alpha-tropomyosin-3 (TPM3) gene was screened in 40 unrelated patients with
      nemaline myopathy (NM). A single compound heterozygous patient was identified
      carrying one mutation that converts the stop codon to a serine and a second
      splicing mutation that is predicted to prevent inclusion of skeletal muscle exon
      IX. TPM3 mutations are a rare cause of NM, probably accounting for less than 3%
      of cases. The severity of cases with TPM3 mutations may vary from severe
      infantile to late childhood onset, slowly progressive forms.

PMID- 12196662
TI  - Asymptomatic cores and paracrystalline mitochondrial inclusions in CADASIL.
AB  - Three siblings with genetically assessed cerebral autosomal dominant arteriopathy
      with subcortical infarcts and leukoencephalopathy (CADASIL) with core-like
      lesions and mitochondrial abnormalities in muscles are described. Involvement of
      the Ryanodine receptor 1 gene was excluded. In the current cases, the relation
      between molecular genetic lesion and muscle fiber abnormalities remains to be
      determined, but the Notch3 gene may influence mitochondrial metabolism.

PMID- 12196663
TI  - Lamin A/C mutations with lipodystrophy, cardiac abnormalities, and muscular
      dystrophy.
AB  - Mutations in the lamin A/C gene are found in Emery-Dreifuss muscular dystrophy,
      limb girdle muscular dystrophy with cardiac conduction disturbances, dilated
      cardiomyopathy with conduction system disease, and familial partial
      lipodystrophy. Cases with lamin A/C mutations presenting with lipodystrophy in
      combination with cardiac and/or skeletal muscle abnormalities are described.

PMID- 12196664
TI  - Irreversible damage to the spinal cord following spinal anesthesia.
AB  - The authors report five patients with damage to the distal spinal cord following
      spinal anesthesia. The patients developed leg weakness and sensory disturbance.
      MRI of the lumbosacral spine showed an abnormal area of high signal within the
      conus medullaris in all patients. Symptoms and signs persisted at 1- to 2.5-year
      follow-ups. Incorrect needle placement and type of needle used are possible
      factors leading to spinal cord injury.

PMID- 12196665
TI  - CSF tau protein phosphorylated at threonine 231 correlates with cognitive decline
      in MCI subjects.
AB  - In this longitudinal study of 77 patients with mild cognitive impairment (MCI),
      the authors analyzed whether levels of tau protein phosphorylated at threonine
      231 (p-tau(231)) in CSF correlate with progression of cognitive decline. High CSF
      p-tau(231) levels at baseline, but not total tau protein levels, correlated with
      cognitive decline and conversion from MCI to AD. Independently, old age and APOE
      epsilon 4 carrier status were predictive as well. Our data indicate that an
      increased p-tau(231) level is a potential risk factor for cognitive decline in
      patients with MCI.

PMID- 12196666
TI  - Valproate embryopathy in three sets of siblings: further proof of hereditary
      susceptibility.
AB  - The fetal valproate syndrome (FVS) is characterized by distinctive facial
      appearance, major and minor malformations, and developmental delay. Generally,
      only a small proportion of prenatally exposed children are affected. The authors
      describe three families in whom the occurrence of FVS in all the siblings
      strongly suggests hereditary susceptibility to valproic acid-induced adverse
      outcome. The risk for recurrence in a subsequent pregnancy may be high and should
      be taken into account in the counseling of parents and in considering drug
      treatment.

PMID- 12196667
TI  - Temporal lobectomy for epilepsy: recovery of the contralateral hippocampus
      measured by (1)H MRS.
AB  - (1)H MRS imaging was obtained from 10 patients with mesial temporal lobe epilepsy
      before and after surgery. After surgery, metabolic recovery in the contralateral
      hippocampus was detected. Preoperatively, reduced N-acetylaspartate (p < 0.04)
      increased after surgery nonsignificantly to equal control values. Cholines
      increased after surgery (p < 0.02) and creatine-phosphocreatine showed a trend to
      higher values. The results suggest that the contralateral hippocampus is affected
      by repeated seizure activity in the ipsilateral hippocampus, rather than presence
      of bilateral mesial temporal sclerosis.

PMID- 12196668
TI  - Interferon beta but not glatiramer acetate therapy aggravates headaches in MS.
AB  - Type and frequency of headaches during immunomodulatory therapy in MS were
      determined in 167 consecutive patients. In a prospective group of 65 patients
      beginning interferon beta therapy, headache frequency and duration increased in
      18% of all and in 35% of patients with pre-existing headache by more than 50%
      during the first 6 months. In two retrospective groups, increased headache
      frequency was reported by 34% of 53 patients on interferon beta, but by only 6%
      of 49 patients during at least 6 months of glatiramer acetate therapy.

PMID- 12196669
TI  - Increased CSF hypocretin-1 (orexin-A) in restless legs syndrome.
AB  - Hypocretin-1 levels were increased in evening CSF samples from subjects with
      restless legs syndrome, indicating altered hypocretin transmission in this sleep
      disorder. Increases in CSF hypocretin-1 levels were most striking in patients
      with early-onset restless legs syndrome.

PMID- 12196670
TI  - Orbital infarction after cocaine use.

PMID- 12196672
TI  - Abnormal cortical development shown by 3D MRI in Prader-Willi syndrome.

PMID- 12196671
TI  - Cluster-like headache associated to a foreign body in the maxillary sinus.

PMID- 12196673
TI  - Alpha-synuclein studies are negative in postencephalic parkinsonism of von
      Economo.

PMID- 12196674
TI  - Unusual entrapment neuropathy in a golf player.

PMID- 12196675
TI  - Quantitative functional measures in MS: what is a reliable change?

PMID- 12196676
TI  - Randomized trial of vigabatrin in patients with infantile spasms.

PMID- 12196677
TI  - Normal IPT and IBZM SPECT in drug naive and levodopa-treated idiopathic restless
      legs syndrome.

PMID- 12196678
TI  - A diffusion-weighted MRI study of acute ischemic distal arm paresis.

PMID- 12196679
TI  - Cerebral vasoconstriction and stroke after use of serotonergic drugs.

PMID- 12196680
TI  - Hypotension and cognitive impairment: selective association in patients with
      heart failure.

PMID- 12196681
TI  - Face modules, face network: the cognitive architecture of the brain revealed
      through studies of face processing.

PMID- 12196682
TI  - Current perspectives in management of chronic asthma in children.

PMID- 12196683
TI  - Early neonatal hyperbilirubinemia using first day serum bilirubin level.
AB  - OBJECTIVE: To evaluate the predictive value of total serum bilirubin (TSB) < or
      =6 mg/dl at 24 +/- 6 hr postnatal age in identifying near term and term infants,
      who do not develop hyperbilirubinemia subsequently. DESIGN: Prospective study.
      SETTING: Tertiary care hospital. METHODS: All healthy neonates with gestation >
      or =35 weeks, in absence of significant illness or Rh hemolysis were included.
      TSB was estimated at 24 +/- 6 hr by micromethod using spectrophotometry. Infants
      were followed up clinically every 12 hr till discharge and then after 48 hr. TSB
      level was estimated again whenever clinical suspicion of jaundice exceeded 10
      mg/dl. Primary outcome was defined as presence of hyperbilirubinemia (TSB > or=
      17 mg/dl) till day five of age. RESULTS: Of the 220 infants, 213 (96.8%) were
      followed up. All infants were exclusively breastfed. Mean age at bilirubin
      estimation was 24.7 +/- 1.9 hr with mean TSB of 5.9 +/- 1.8 mg/dl. Clinically
      detectable jaundice was present in 164 (77%) and hyperbilirubinemia occurred in
      22 (10.3%) infants. A TSB level of < or = 6 mg/dl at 24 +/- 6 hr was present in
      136 (63.8%) infants and only one infant developed hyperbilirubinemia subsequently
      (probability < 1%). In the remaining 77 (36.1%) infants, with TSB >6 mg/dl,
      subsequent hyperbilirubinemia developed in 21 (27.2%) (sensitivity 95%,
      specificity 70.6%, positive predictive value 27.2%, negative predictive value
      99.3%, likelihood ratio of positive test 3.23 and likelihood ratio of negative
      test 0.07). Babies with TSB levels higher than 6 mg/dl had a significant risk of
      developing hyperbilirubinemia (relative risk 38; 95% confidence interval 6-1675).
      CONCLUSION: A TSB level of < or = 6 mg/dl at 24 +/- 6 hr of life predicted
      neonates who would not develop hyperbilirubinemia.

PMID- 12196684
TI  - Asthma and the school going child.

PMID- 12196685
TI  - Cytokine production by peripheral blood mononuclear cells from patients with
      juvenile idiopathic arthritis.

PMID- 12196686
TI  - Comparison of HemoCue method with cyanmethemoglobin method for estimation of
      hemoglobin.

PMID- 12196687
TI  - Clinical characteristics [correction of characterstics] and outcome of children
      and adolescents with conversion disorder.

PMID- 12196688
TI  - Central venous catheter colonization and related bacteremia in pediatric
      intensive care unit.

PMID- 12196689
TI  - Cerebro-oculo-facio-skeletal syndrome in a neonate.

PMID- 12196690
TI  - Sinus histiocytosis with massive lymphadenopathy in children.

PMID- 12196691
TI  - Renal failure from obstructive fungal mycetoma and fungal sepsis in an infant.

PMID- 12196692
TI  - Hyperekplexia: a non-epileptic startle disorder.

PMID- 12196693
TI  - Shigella septicemia.

PMID- 12196694
TI  - Metatropic dystrophy.

PMID- 12196695
TI  - Labial fusion.

PMID- 12196696
TI  - Ehler-Danlos syndrome.

PMID- 12196697
TI  - HBV carrier rate in India.

PMID- 12196699
TI  - Neonatal hyperbilirubinemia.

PMID- 12196700
TI  - Neonatal hyperbilirubinemia.

PMID- 12196702
TI  - Consensus statement on the management of UTI.

PMID- 12196704
TI  - Formula milks: contamination, toxicity and physiological imbalances.

PMID- 12196705
TI  - Necessity to establish new risk assessment and risk communication for human fetal
      exposure to multiple endocrine disruptors in Japan.
AB  - Our recent study clearly shows that fetuses are exposed to multiple chemicals
      including endocrine disruptors in Japan. Although the embryo and fetus stages are
      the most sensitive period to chemicals in humans' life cycle, the health effects
      of the chemicals such as endocrine disruptors to them are largely unknown. The
      conventional risk assessment method cannot assess the risk to fetuses precisely.
      Now we need a new risk assessment, in which the target is fetuses and not the
      adults, in addition to the conventional risk assessment. At the same time, we
      also need a new strategy to practically eliminate the risk for the future
      generations. To make the strategy effective, we suggest a new approach to reduce
      the risk and avoid the possible adverse health effects, using primary, secondary
      and tertiary preventions as they are used in public health. We also suggest a new
      concept of "pre-primary prevention" to reduce the risk for fetuses. Furthermore,
      to make this method even more practical, we suggest a new risk communication
      method. In this paper, we present a framework of risk avoidance of multiple
      chemical exposure to fetuses.

PMID- 12196706
TI  - Developmental toxicity of estrogenic chemicals on rodents and other species.
AB  - Antenatal sex-hormone exposure induces lesions in mouse reproductive organs,
      which are similar to those in humans exposed in utero to a synthetic estrogen,
      diethylstilbestrol. The developing organisms including rodents, fish and
      amphibians are particularly sensitive to exposure to estrogenic chemicals during
      a critical window. Exposure to estrogens during the critical period induces long
      term changes in reproductive as well as non-reproductive organs, including
      persistent molecular alterations. The antenatal mouse model can be utilized as an
      indicator of possible long-term consequences of exposure to exogenous estrogenic
      compounds including possible environmental endocrine disruptors. Many chemicals
      released into the environment potentially disrupt the endocrine system in
      wildlife and humans, some of which exhibit estrogenic activity by binding to the
      estrogen receptors. Estrogen responsive genes, therefore, need to be identified
      to understand the molecular basis of estrogenic actions. In order to understand
      molecular mechanisms of estrogenic chemicals on developing organisms, we are
      identifying estrogen responsive genes using cDNA microarray, quantitative RT-PCR,
      and differential display methods, and genes related to the estrogen-independent
      vaginal changes in mice induced by estrogens during the critical window. In this
      review, discussion of our own findings related to endocrine distuptor issue will
      be provided.

PMID- 12196707
TI  - Endocrine disruptor issues in Japan.
AB  - Monitoring of environmental chemicals in Japan has revealed that several
      endocrine active chemicals are in river water, sediments, and wildlife as well as
      in the human umbilical cord. In 2001, risk assessments of tributyltin and
      nonylphenol have been conducted by the Ministry of the Environment, Japan. Risk
      assessments of di(2-ethylhexyl)phthalate and di-isononyl phthalate have also been
      performed by the Ministry of Health, Labour and Welfare using a toxicological
      point of view in 2001. In this review, an overview of recent progress in
      endocrine disruptor research in Japan will be provided.

PMID- 12196708
TI  - Enrichment of fetal cells from maternal blood by magnetic activated cell sorting
      (MACS) with fetal cell specific antibodies: one-step versus two-step MACS.
AB  - We report here the results of fetal cell enrichment from maternal blood in 58
      pregnant women by the use of magnetic activated cell sorting (MACS) with
      erythroblast-specific and/or maternal cell specific antibodies. Two approaches
      were compared; one-step MACS to enrich CD71+ (a membrane-bound marker) or GPA+
      (another marker, glycophorin A) fetal cells versus two-step MACS to deplete CD14+
      maternal cells and subsequently to enrich fetal (CD71+ or GPA+) cells. The
      existence of fetal cells was ensured by both FISH with Y-specific probes and
      karyotyping of respective amniotic and/or chorionic vullus cells, the results
      being applied for comparison of detection rate for XY fetuses between the two
      MACS procedures. In 24 (38.8%) of the 58 blood samples examined, Y-positive cells
      were observed by FISH, whereas there were 38 true XY fetuses later confirmed by
      karyotyping, including two cases of 47,XY,+21. On the other hand, in Y-negative
      cells by FISH, there were two cases of 47,XX,+18. The average number of cells
      sorted did not differ among one-step MACS procedures with anti-CD14, anti-CD71
      and anti-GPA antibodies. With the latter, 12 (75%) of 16 Y-positive fetuses were
      detected, while only one (20%) of 5 Y-positive fetuses was detected by two-step
      MACS with anti-CD14/anti-GPA antibodies. The detection rate significantly varied
      (p = 0.0024) between the two procedures, although the numbers of cases examined
      were small. There was no statistical difference (p > 0.05) between one-step and
      two-step MACS with other combinations of antibodies. These findings indicate that
      one-step MACS using the anti-GPA antibody is more effective than two step MACS
      for enrichment of fetal cells from maternal blood.

PMID- 12196709
TI  - A selective loss of small-diameter myelinated optic nerve axons in rats
      prenatally exposed to ethanol.
AB  - Pregnant rats were fed an ethanol-containing liquid diet between gestational days
      10 and 21. The optic nerves of their litters at 49 days of age were examined
      using quantitative stereological procedures. Cross-sectional areas of the optic
      nerve in ethanol-exposed rats were significantly smaller than those in controls.
      This was reflected in the reduced number of myelinated fibers, but not of non
      myelinated fibers. The size distribution histogram indicated a decreased number
      of small axonal-diameter myelinated fibers in ethanol-exposed rats. The results
      suggested optic nerve hypoplasia in ethanol-exposed rats characterized by a
      selective loss of small-diameter myelinated fibers.

PMID- 12196710
TI  - The initial development of motor neurons in the neural tube of rat embryos.
AB  - The time of origin of motor neurons and their distribution in the spinal cord was
      studied in rat embryos by combining whole-embryo culture and the Islet-1
      immunostaining technique. Cells immunostained for Islet-1 appeared in the trunk
      neural tube by 27 hours (corresponding to E10.625) in culture of E9.5 embryos, at
      which time the cell number of the neural tube in a transverse section was about
      200. When the neural tube retarded developmentally by lithium treatment, the time
      of appearance of the motor neurons was delayed to 33 hours in culture
      (corresponding to E10.875), but the cell number of the neural tube was about 200.
      After the initial appearance of motor neurons in the ventral aspect of the neural
      tube, they distributed in a group in the periphery of the basal plate by 48 hours
      (corresponding to E11.5) in culture, although in the retarded neural tube the
      number of motor neurons was small and they did not form a cluster. The percentage
      of Islet-1-positive cells at the point of the same cell number of the trunk
      neural tube in the transverse section was higher in the retarded embryos than in
      controls. These results suggest that motor neurons begin to appear when the cell
      number of the neural tube in the transverse section becomes about 200 and their
      initial development is more stable than overall neural tube development.

PMID- 12196712
TI  - A case of midline cervical cleft.
AB  - Midline cervical cleft is a rare congenital developmental anomaly of the ventral
      neck. Less than 100 cases have been reported in published journals to date
      (Ayache et al., 1997). It is usually found as congenital scar-like skin defect or
      cord-like contractive abnormality of the skin at the ventral neck. Unlike "median
      cervical cyst" or "lateral cervical cyst"  midline cervical cleft usually has no
      anatomical association with the hyoid bone. We will present a case of midline
      cervical cleft without fistula but with very small protuberant tissue. The
      subject was operated at the age of 5 months. We will discuss the clinical aspect
      and surgical management of this infrequent anomaly.

PMID- 12196711
TI  - Perinatal development of the rat hip joint with restrained fetal movement.
AB  - We compared the structures of the femoral head (FH) of neonates between normal
      and operated legs with restrained fetal movement using an exo utero technique. At
      embryonic day (E) 16.5, one hind limb was sutured onto the embryonic membrane and
      the fetuses were allowed to develop exo utero until the term (E22.5). There was
      no significant difference in the largest diameter of the FH between the non
      operated and operated side FH in the operated neonates and the FH of the non
      operated neonates. By scanning electron microscopy, roughness and collagen fiber
      bundles, which were detected on the surface of the operated side FH at E18.5,
      disappeared at E22.5. However, the operated side FH was deformed and the surface
      cell arrangement was more irregular than that of the controls at E22.5 by light
      microscopy. These results suggest that the abnormality of cell arrangement caused
      by the restraint of fetal movement may induce the deformity and irregularity of
      the FH surface, although this operation may not disturb the basic cellular
      activities such as cell proliferation as well as the secretion of cartilage ma
      trix and collagen fibers. To further investigate the recovery process in the
      operated newborns after releasing the restraint, we bred them artificially for a
      considerable period after birth. The operated side FH surface of the neonate bred
      for 45 hours was smoother than that at E22.5 and similar to that of the non
      operated side FH. This result suggests that the proper movement of the
      extremities after birth may recover the deformity caused by restrained fetal
      joint movement.

PMID- 12196713
TI  - Results of questionnaires concerning breast cancer surgery in Japan: an update in
      2000.

PMID- 12196714
TI  - A survival benefit from locoregional therapy: implication for Halsted's
      hypothesis.

PMID- 12196715
TI  - The role of neoadjuvant chemotherapy for breast cancer treatment.
AB  - Neoadjuvant chemotherapy has become popular, especially for patients with
      advanced breast cancer. The pros and cons of neoadjuvant chemotherapy for
      treating breast cancer patients are reviewed. The advantages of neoadjuvant
      chemotherapy are 1) overall survival and recurrence-free survival rate are the
      same as post-operative chemotherapy, 2) serves as an in vivo sensitivity test, 3)
      increases the rate of breast conserving therapy, 4) facilitates the study of
      cancer biology. On the other hand, the disadvantages of neoadjuvant chemotherapy
      are 1) it modifies the stage, 2) treatment delay of PD cases, 3) residual
      intraductal component may be left behind after breast conserving surgery, 4)
      there are some cases of over-treatment. Combination chemotherapy is one possible
      way to increase the pathological CR rate, although the optimal order and cycles
      have not been determined. To avoid residual cancer cells after breast conserving
      surgery, the shrinkage pattern should be evaluated by MRI. Core needle biopsy
      should be performed before neoadjuvant chemotherapy to avoid over-treatment. It
      is essential to develop more effective regimens and stratify patients based on
      predictive factors.

PMID- 12196716
TI  - Efficacy of 3D-MR mammography for breast conserving surgery after neoadjuvant
      chemotherapy.
AB  - BACKGROUND: One of the main roles of neoadjuvant chemotherapy for breast cancer
      is to shrink large tumors to increase patient eligibility for breast conserving
      surgery. Three dimensional MR Mammography (3D-MRM) can detect tumor extension
      more accurately compared with mammography and Ultrasonography (US). Therefore,
      the shrinkage pattern observed on 3D-MRM was analyzed with regard to several
      pathological factors. METHODS: A total of 27 breast cancer cases were examined by
      3D-MRM before and after neoadjuvant chemotherapy. The volume reduction and
      shrinkage patterns were assessed and compared with the pathological diagnosis.
      RESULTS: There were two shrinkage patterns. Twelve of 25 evaluable breast cancers
      (48%) showed a concentric shrinkage pattern while 13 cases (52%) showed a
      dendritic shrinkage pattern. The cases with concentric shrinkage were good
      candidates for breast conserving surgery, But tumors showing dendritic shrinkage
      often had positive margins necessitating mastectomy. Pathologically, tumors with
      a papillotubular pattern, Estrogen receptor (ER) positivity, low nuclear grade
      and c-erbB 2 negativity tended to show dendritic shrinkage. CONCLUSIONS: 3D-MRM
      is a useful modality for evaluating whether breast conserving surgery can be
      safely done in the neoadjuvant setting.

PMID- 12196717
TI  - Breast-conserving treatment after neoadjuvant chemotherapy in large breast
      cancer.
AB  - Several recent trials have demonstrated that neoadjuvant chemotherapy can allow
      more patients to successfully undergo breast-conserving treatment (BCT), and does
      not confer a survival disadvantage compared with standard adjuvant chemotherapy.
      In addition, the pathological response of primary breast tumors to neoadjuvant
      chemotherapy appears to be a surrogate marker for patient outcome. In our series,
      during the period from May 1995 to December 2000, 86 patients with tumors between
      3.1 and 6.0 cm in diameter received epirubicin-based neoadjuvant chemotherapy.
      There were 55 (64.0%) responders and ultimately 64 patients (74.4%) were treated
      with BCT. The margin positive rate was 14.1%(9/64), similar to the rate after BCT
      for early-stage breast cancers, the largest diameter of which was smaller than 3
      cm. At a median follow-up of 30 months, only 3 patients in the BCT group have
      developed local recurrence; the local recurrence rate appears to be comparable to
      that after BCT for early stage breast cancers. Long term follow-up is required,
      however, to establish whether this procedure is a safe alternative to mastectomy
      for patients with large breast cancers.

PMID- 12196718
TI  - Analysis of gene expression involved in brain metastasis from breast cancer using
      cDNA microarray.
AB  - BACKGROUND: Brain metastases occur in 15% to 30% of breast cancer patients,
      usually as a late event. The patterns of metastases to different organs are
      determined by the tumor cell phenotype and interactions between the tumor cells
      and the organ environment. METHODS: We investigated the gene expression profile
      occurring in brain metastases from a breast cancer cell line. We used cDNA
      microarrays to compare patterns of gene expression between the mouse breast
      cancer cell line Jyg MC (A) and a subline that often metastasis to brain, (B).
      RESULTS: By Microarray analysis about 350 of 21,000 genes were significantly up
      regulated in Jyg MC (B). Many candidate genes that may be associated with the
      establishment of brain metastasis from breast cancer were included.
      Interestingly, we found that the expression of astrocyte derived cytokine
      receptors (IL-6 receptor, TGF-beta receptor and IGF receptor) were significantly
      increased in Jyg MC (B) cells. These results were confirmed by RT-PCR.
      CONCLUSIONS: These results suggest that cytokines produced by glial cells in vivo
      may contribute, in a paracrine manner, to the development of brain metastases
      from breast cancer cells.

PMID- 12196719
TI  - Mutation analysis of the mel-18 gene that shows decreased expression in human
      breast cancer cell lines.
AB  - BACKGROUND: Mammalian mel-18 is a member of the polycomb group, and it acts as a
      transcriptional repressor with DNA binding activity. Murine mel-18 negatively
      regulates the cell cycle through the c-myc/cdc25 cascade, and mice
      haploinsufficient for mel-18 develop mammary gland tumors. In addition, the human
      homolog of mel-18 is located at 17q, on which candidate tumor suppressor genes
      for breast cancer have been suggested for a long time. These observations
      indicate that the mel-18 gene may be a tumor suppressor gene for breast cancer.
      To investigate this possibility, we examined the expression of mel-18 mRNA in
      human breast cancer cell lines and searched for mel-18 gene mutations in sporadic
      and familial breast cancers. METHODS: The expression of mel-18 mRNA was examined
      in five breast cancer cell lines by RT-PCR, and somatic and germline mutations of
      the mel-18 gene were analyzed by the PCR-SSCP and sequence methods in 48 sporadic
      breast cancers, including 16 cases with loss of heterozygosity (LOH) at the mel
      18 locus, and in 23 cases from 18 breast cancer families, respectively. RESULTS:
      We found that most cell lines examined here showed decreased expression of mel-18
      mRNA, however, no alteration other than a single nucleotide change that did not
      lead to amino acid alteration in one patient was identified. CONCLUSION: Our
      results reveal that mel-18 gene mutations are exceedingly rare in human breast
      cancers, and a reduction of mel-18 expression in human breast cancer cell lines
      would support a role for mel-18 haploinsufficiency in breast carcinogenesis.

PMID- 12196720
TI  - In vitro regulation of vascular endothelial growth factor by estrogens and
      antiestrogens in estrogen-receptor positive breast cancer.
AB  - BACKGROUND: The effects of antiestrogens on angiogenesis in breast cancer are not
      fully defined. In this study we investigated the in vitro effects of
      antiestrogens at different concentrations on vascular endothelial growth factor
      (VEGF) production in estrogen receptor (ER)-positive breast cancer cells.
      METHODS: The dose-dependent effects of 17beta-estradiol (E2), 4-hydroxytamoxifen
      (4OHT), and ICI182,780 were analyzed both with reference to growth rates and VEGF
      protein production using enzyme-linked immunosorbent assay (ELISA) in MCF-7
      cells. RESULTS: E2 stimulated both the growth rates and VEGF production of MCF-7
      cells in the same manner. Although 4OHT stimulated the growth rates as an
      agonistic effect in an estrogen-free media at levels ranging from 1 nM to 1 micro
      M, it did not stimulate VEGF expression at the same levels except for at 1 micro
      M. Although 4OHT had a weak agonistic effect on VEGF production at 1 micro M in
      an estrogen-free media, it significantly inhibited E2-stimulated VEGF production
      at the same level. A cytotoxic effect was observed with 10 micro M 4OHT that
      paradoxically caused a prominent increase in VEGF production. ICI182,780 had no
      significant effects on the growth rates or VEGF production in this cell line.
      CONCLUSIONS: These results support the hypothesis that tamoxifen could inhibit
      angiogenesis induced by estrogens in ER-positive breast cancer cells.

PMID- 12196721
TI  - Histological and immunohistochemical analysis of apocrine breast carcinoma.
AB  - BACKGROUND: There are few data regarding the biological characteristics of
      apocrine breast carcinoma in the literature due to its rarity and controversy
      over its definition. We analyzed the histopathological characteristics and tumor
      biology of apocrine breast carcinomas with regard to histological grade, p53,
      HER2, bcl-2, MIB-1 and hormone receptor status. PATIENTS AND METHODS: A
      consecutive series of 24 female apocrine breast carcinoma patients were the
      primary source of these retrospective data. Background factors including
      histological grade, nodal status and lymphatic invasion by tumor cells were
      analyzed. Immunohistochemical staining for p53, HER2, MIB-1, bcl-2, estrogen
      receptor (ER) and progesterone receptor (PR) was carried out on formalin-fixed,
      paraffin embedded specimens. RESULTS: Older age and postmenopausal status were
      observed more frequently in patients with apocrine breast carcinoma than those
      with invasive ductal carcinoma. Apocrine breast carcinoma also showed relatively
      lower histological grade than invasive ductal carcinoma. Nuclear accumulation of
      p53, HER2 overexpression, bcl-2 and MIB-1 index were observed in 29% (7/24),
      33%(8/24), 25%(6/24) and 29% (7/24) of cases, respectively. Positivity for ER and
      PR was present in 17% (4/24) and 17% (4/24) of cases, respectively. CONCLUSIONS:
      Apocrine breast carcinoma tended to show low MIB-1 index, low bcl-2 expression
      and low positive rate of hormone receptors. There was no correlation between the
      three types of apocrine carcinoma and the positivity rate of p53, HER2, bcl-2,
      MIB-1 and hormone receptor status.

PMID- 12196722
TI  - UCN-01 (7-hydroxystaurosporine) inhibits the growth of human breast cancer
      xenografts through disruption of signal transduction.
AB  - BACKGROUND: 7-Hydroxystaurosporine (UCN-01), originally isolated as a
      phospholipid-dependent protein kinase C inhibitor, has been shown to have
      antitumor activity against several human cancer cell lines. UCN-01 inhibits cell
      cycle progression from the G1 to S phase by inhibition of cyclin-dependent kinase
      (CDK) activity and induction of intrinsic CDK inhibitor protein, leading to
      dephosphorylation of retinoblastoma (Rb) protein. MATERIALS AND METHODS: The
      antitumor activity of UCN-01 has been investigated against three human breast
      carcinoma strains serially transplanted into nude mice, including estrogen
      dependent MCF-7, Br-10, and estrogen-independent MX-1. When the inoculated tumors
      started growing exponentially, UCN-01 (7.5 mg/kg) was administered
      intraperitoneally on five consecutive days a week for 2 weeks. The antitumor
      effect was evaluated as the lowest T/C ratio (%) during the experiments, where T
      was the relative mean tumor weight of the treated group and C was that of the
      control group. At the end of UCN-01 administration expression of p21, a protein
      of the CDK inhibitor family, and phosphorylated and dephosphorylated Rb protein
      was detected by Western blotting using treated and control tumors. RESULTS: UCN
      01 had activity against MCF-7 and Br-10, with the lowest T/C ratios of 25.0% and
      27.0%, respectively, while MX-1 was resistant to UCN-01 with a T/C ratio of
      65.9%. The antitumor spectrum of UCN-01 was different from that of other
      conventional agents such as doxorubicin and cyclophosphamide which were
      ineffective against Br-10 but were active against MX-1. Although p21 was induced
      in three tested strains by UCN-01, little dephosphorylated Rb protein was
      expressed in MX-1 compared with Br-10 and MCF-7 (in vitro). CONCLUSION: UCN-01
      appeared to be a promising agent for the treatment of breast cancer, with a
      different mode of action and antitumor spectrum from other currently available
      antitumor drugs.

PMID- 12196723
TI  - Histological subtypes of ductal carcinoma in situ of the breast.
AB  - BACKGROUND: It has become common to divide ductal carcinoma in situ (DCIS) of the
      breast into two main groups, comedo or noncomedo by tumor morphology. But
      noncomedo DCIS can be further stratified into several morphological patterns that
      exhibit several different growth patterns and most DCIS lesions have more than
      one pattern. In this study, DCIS elements were classified by morphological
      pattern and the association between predominant or recessive elements of DCIS
      lesions and clinicopathological findings was evaluated. METHODS: DCIS lesions
      from 46 patients were studied regarding the histological architectural patterns:
      comedo, cribriform, papillary, solid and micropapillary. The predominant
      architectural pattern which comprised more than 50% of the cells of the cancerous
      lesion was defined as the major element of the tumor and minor elements consisted
      of less than 50% but more than 25% of cells comprising the tumor. RESULTS: Of 24
      tumors containing a comedo pattern as the major or minor element, 9 (38%) had
      microscopic intraductal spread over 2 cm and 11 (46%) had involvement of lobules,
      which was significantly higher than that observed in other types. Of 20 tumors
      containing a cribriform pattern as the major or minor element, 8 (40%) had
      microscopic intraductal spread over 2 cm and 9 (45%) had involvement of lobules,
      which was significantly higher than that seen in other types. Of 10 tumors
      containing a papillary type as the major or minor element, 5 (50%) had discrete
      multicentric lesions in the ipsilateral or contralateral breast, which was
      significantly higher than that seen in other types. CONCLUSIONS: DCIS lesions
      containing a comedo or cribriform element are more likely to have microscopic
      spread and involvement of lobules and DCIS lesions containing a papillary element
      are likely to be multicentric, whether the pattern are predominant in the tumor
      or not.

PMID- 12196724
TI  - False-positive helical CT findings of multifocal and multicentric breast cancer:
      is attenuation of tumor useful for diagnosing enhanced lesions?
AB  - OBJECTIVE: To analyze helical CT false-positive multifocal breast cancers and to
      assess the relevance of the attenuation of tumors for diagnosing enhanced
      lesions. METHODS: Helical CT studies of 156 invasive breast cancers before breast
      conserving surgery were examined. A lesion was defined as positive if focal
      enhancement was detected by CT within 100 seconds after contrast material
      administration. The attenuation and enhancement percent ratio [(post-contrast
      value/pre-contrast value)%] were obtained. Attenuation of false-positive and
      malignant lesions was compared. RESULTS: Helical CT enabled the detection of all
      156 invasive tumors with 95 intraductal tumor extensions. The sensitivity and
      specificity of multifocal/multicentric disease detection by helical CT were 69%
      and 90%, respectively. False-positive multifocal/multicentric findings were
      obtained in 11 (7%) of 156 cases. The mean value of the enhancement percent ratio
      of the index tumors was 237%. Significant differences in the attenuation on post
      contrast enhanced scans between the enhanced lesions (index tumors; mean, 82 HU),
      the true-positive multifocal/multicentric lesions (mean, 73 HU), the false
      positive multifocal/multicentric lesions (mean, 87 HU) and normal breast tissue
      (mean, 32 HU) were found (p<0.0001). The attenuation of the true-positive
      multifocal/multicentric lesions on post-contrast enhanced scans was significantly
      less than that of the false-positive multifocal/multicentric lesions (p=0.03).
      CONCLUSION: Attenuation of tumor is not useful for differential diagnosis of
      enhanced lesions on helical CT of the breast. The presence of enhancement alone
      does not always indicate a malignant lesion.

PMID- 12196725
TI  - MR-axillography oriented surgical sampling for assessment of nodal status in the
      selection of patients with breast cancer for axillary lymph nodes dissection.
AB  - BACKGROUND: We have reported that magnetic resonance axillography (MR
      axillography) is the best method for assessing lymph node size and representing
      the relation of the lymph node to normal anatomy. METHODS: The four largest nodes
      on MR-axillography were sampled in 62 consecutive patients with breast cancer
      undergoing axillary clearance. Axillary clearance yielded a mean of 17.0 (range 5
      28) nodes. RESULTS: A method of preliminary sampling of four nodes in the axilla
      oriented by MR-axillography was assessed in all cases, 22 of whom were
      histologically node positive. Based on the sampled nodes, lymph node metastases
      were detected in 20 of 22 (91%) of the node-positive patients. Based on the
      sampled nodes, of the 19 patients with macrometastatic nodes, lymph node
      metastases were detected in all 19 (100%), but only in 1 of the 3 (33%) patients
      with only one micrometastatic node. CONCLUSIONS: This experience indicates that
      sampling the four largest nodes by MR-axillography orientation accurately
      identifies patients with macrometaststic nodes. This result may be comparable to
      that of surgical sampling performed by the most skilled surgeons.

PMID- 12196726
TI  - Concordance in pathological response to neoadjuvant chemotherapy between invasive
      and noninvasive components of primary breast carcinomas.
AB  - BACKGROUND: Invasive breast carcinomas are composed of invasive and noninvasive
      components in varying proportions and sometimes the two components show different
      histopathological responses to chemotherapy, however there has been no study as
      yet comparing the pathological response to chemotherapy of invasive and
      noninvasive components. PATIENTS AND METHODS: A consecutive series of 100 women
      neoadjuvant chemotherapy with doxorubicin and docetaxel every three weeks before
      surgery. After the chemotherapy, surgically resected specimens were studied
      histologically according to the criteria of the Japanese Breast Cancer Society.
      RESULTS: Five cases (5/100; 5%) were determined to show Grade 3 pathological
      response, and 28 cases (28/100; 28%) showed Grade 2 response. There were 6 Grade
      3 (6/96; 6%) and 18 Grade 2 (18/96; 19%) invasive component cases. There were 7
      Grade 3 (7/82; 9%) and 18 Grade 2 (18/82; 22%) cases showing pathological
      response in the noninvasive component. With regard to pathological response,
      there was a strong correlation between the invasive and noninvasive components
      (p<0.001). There was also a correlation in pathological response between the
      invasive component and axillary lymph nodes in individual cases (p=0.02). There
      was no correlation between the response of the noninvasive component and axillary
      lymph nodes. By multivariate analysis, the overall primary tumor response was
      reflected by the histological response of the invasive component in the primary
      breast carcinoma. CONCLUSION: We suggest that the pathological response of the
      invasive component of breast carcinoma should be evaluated, which might provide
      more accurate information for prognosis and treatment decisions.

PMID- 12196728
TI  - Case reports of malignant mucocele-like lesions.
AB  - Mucocele-like lesions (MLL) of the breast have been reported as extremely rare as
      well as benign, but now it is believed they can be both malignant and benign.
      This paper describes two cases of malignant MLL, both subjected to
      immunohistochemical staining. Case 1: A 42-year-old woman with multiple malignant
      MLLs without evidence of a mass at presentation to our hospital after biopsy, but
      whose ultrasonogram showed small multiple hypoechoic lesions. Case 2: A 70-year
      old woman, whose left breast cancer was found on routine mammography after
      modified radical mastectomy for right breast cancer. Pathologically, MLL with
      intraductal carcinoma was diagnosed. Case 1 underwent two lumpectomies in 3
      years, but even now new lesions have developed. However, the patient refused to
      have another operation. C-erbB2 was negative in both cases. When malignant MLL is
      histologically of low grade, excisional biopsy is sufficient for a single MLL
      with intraductal carcinoma, while it may be necessary to perform a subcutaneous
      mastectomy for multiple lesions.

PMID- 12196727
TI  - A case of pulmonary metastasis from breast cancer following an 18-year disease
      free interval that responded to tamoxifen treatment.
AB  - A 61-year-old woman was admitted to our hospital with an abnormal shadow on chest
      roentgenogram. She had undergone a radical mastectomy for right breast cancer 18
      years previously. Since pleural dissemination was noted at the time of
      thoracotomy, only tumor biopsy was performed. Although a decisive diagnosis could
      not be obtained histologically, the tumor resembled breast cancer and the
      estrogen receptor status was positive. She underwent post-operative chemotherapy
      and tamoxifen treatment. After tamoxifen treatment, complete response was
      observed. The patient is now doing well without recurrence about 10 years after
      thoracotomy. Based on the clinical course, we obtained both a definitive
      diagnosis and complete remission.

PMID- 12196730
TI  - Why are helicopters so expensive? Part 4.

PMID- 12196731
TI  - Air medical transport of a pediatric patient with a pulmonary artery catheter and
      inhaled nitric oxide.

PMID- 12196735
TI  - Do consortiums work?

PMID- 12196737
TI  - Flight crews' use of digital cameras.

PMID- 12196738
TI  - Aftermath.

PMID- 12196739
TI  - Life beyond MUDPILES.

PMID- 12196740
TI  - Air transport of the IABP patient. Intra-Aortic Balloon Pump.
AB  - The intra-aortic balloon pump (IABP) has evolved into an easily transported,
      computer-driven device for invasively assisting circulation. This article reviews
      the use of the IABP during interfacility patient transport by air. Air transport
      of the IABP-dependent patient creates unique clinical, logistical, and technical
      challenges. We review the function and clinical application of IABP in various
      air transport conditions. We also identify the complications of intra-aortic
      balloon pumping, such as hemorrhage, loss of trigger signals, cardiac arrest, and
      atmospheric pressure changes, and offer solutions. The effective clinical use of
      IABP in the air transport environment involves more than familiarity with the
      device and implications for its use; rapid identification of problems and
      implementation of solutions are required for successful transport and patient
      outcomes.

PMID- 12196741
TI  - The molecular basis of hereditary palmoplantar keratodermas.
AB  - In recent years, the gene defects causing many types of hereditary palmoplantar
      keratoderma have been discovered. These genes encode a variety of proteins
      involved in the terminal differentiation of keratinocytes and the formation of
      the cornified cell envelope. In this article, we review the molecular defects
      underlying various palmoplantar keratodermas with particular attention to the
      role of these molecules in the terminal differentiation of palmoplantar
      epidermis. Of the proteins involved in keratodermas, loricrin, keratins, and
      desmosomal proteins provide the protein structure of the cornified cell envelope.
      Connexins form intercellular gap junctions, which regulate ionic calcium signals
      necessary for the expression of the proteins that form the cornified cell
      envelope. Cathepsins likely mediate enzymatic processes necessary for the
      formation and dissolution of the cornified cell envelope. The clinical phenotypes
      produced by various mutations affecting these proteins are discussed vis-a-vis
      data from genetic, cellular, and molecular experiments.

PMID- 12196742
TI  - The antimicrobial peptide LL-37 is expressed by keratinocytes in condyloma
      acuminatum and verruca vulgaris.
AB  - BACKGROUND: LL-37 is a peptide belonging to the cathelicidin family of
      antimicrobial peptides. Recent investigations have suggested that the expression
      of antimicrobial peptides is an important mechanism for resistance to microbial
      infection. OBJECTIVE: The aim of this study was to determine whether LL-37 is
      expressed in papillomavirus-infected epidermis from patients with condyloma
      acuminatum or verruca vulgaris. METHODS: Biopsy specimens from 3 patients with
      condyloma and 2 patients with verruca vulgaris and 6 normal skin samples were
      studied by immunostaining with an antibody specific to LL-37 and control rabbit
      serum. Western blots were performed on skin extracts from normal skin and
      verrucae. RESULTS: A large increase in the expression of LL-37 was seen within
      keratinocytes of all involved samples and in the extracts of verrucae analyzed by
      Western blot. CONCLUSION: This study shows the antimicrobial peptide LL-37 is
      induced within the epidermis during the development of verruca vulgaris. This
      expression represents a previously unknown immunologic response to papillomavirus
      infection and may represent an important step in the pathogenesis of this
      disorder.

PMID- 12196743
TI  - Penile lesions and human papillomavirus in male sexual partners of women with
      cervical intraepithelial neoplasia.
AB  - BACKGROUND: Genital human papillomavirus infection (HPV) is causally associated
      with cervical carcinomas and premalignant lesions. Limited information is
      available about the prevalence of HPV and penile lesions in male sexual partners
      of women with cervical intraepithelial neoplasia (CIN). OBJECTIVE: The aim of
      this study was to identify the presence of penile lesions and HPV in penile
      scrapings from male sexual partners of women with CIN. METHODS: One hundred
      seventy-five male sexual partners of women with CIN were screened by peniscopy
      after acetowhite staining and HPV testing on penile scrapings. RESULTS: Penile
      lesions were seen in 68% of the male sexual partners. More than one lesion type
      was diagnosed in 15%. Flat lesions, papular lesions, and condylomata acuminata
      were seen in 83%, 29%, and 4%, respectively. HPV was detected in 59% of the
      penile scrapings, containing mainly oncogenic HPV types. When penile lesions were
      present at peniscopy, 67% of penile scrapings were positive for HPV, whereas 37%
      were HPV-positive when no lesions were visible. CONCLUSIONS: Penile lesions are
      frequently found in sexual partners of women with CIN. Most of these lesions are
      subclinical (ie, only visible after acetowhite staining) and are often associated
      with the presence of high-risk HPV, indicating that male sexual partners of women
      with CIN might constitute a reservoir for high-risk HPV.

PMID- 12196744
TI  - Treatment of pemphigus with intravenous immunoglobulin.
AB  - BACKGROUND: Intravenous immunoglobulin (IVIg) has recently been advocated as a
      treatment for pemphigus, but the results of published studies are in conflict.
      This study was conducted to re-examine the effectiveness of IVIg for the
      immediate control of active disease and to study the mechanisms of its action.
      METHODS: Six patients with active pemphigus vulgaris unresponsive to conventional
      therapy with high doses of corticosteroids were treated with IVIg (400 mg/kg per
      day for 5 days) and concurrently given cyclophosphamide (100-150 mg/d). The
      primary end points were healing of skin lesions and changes in the level of
      intercellular antibodies and steroid dose. RESULTS: New lesions ceased to form
      within 1 week of initiating IVIg therapy, and within 2 weeks the extent of
      existing skin lesions was reduced by 80% or more in all but one patient. Within 3
      weeks, steroid doses were reduced by an average of 41%. The improvement was more
      rapid than that in patients previously treated with similar doses of steroids and
      cytotoxic agents at the same institution. Clinical improvement was associated
      with a rapid decline in pemphigus antibodies whose levels decreased by 72% within
      1 week of initiation of IVIg therapy. The rapidity and extent of this decline
      were similar to those achieved with intensive plasmapheresis. The decline was not
      due to blocking the synthesis or the immunologic activity of intercellular
      antibodies by IVIg, suggesting that it resulted from increased immunoglobulin
      catabolism. CONCLUSIONS: These results indicate that IVIg can effectively and
      rapidly control active pemphigus unresponsive to conventional therapy and suggest
      that the mechanism of its action is decreasing serum levels of intercellular
      antibodies.

PMID- 12196745
TI  - Total skin electron radiation in the management of mycosis fungoides: Consensus
      of the European Organization for Research and Treatment of Cancer (EORTC)
      Cutaneous Lymphoma Project Group.
AB  - Radiotherapy has been successfully implemented in the treatment of mycosis
      fungoides (MF) for almost a century. With the development of the modern linear
      accelerator, it has become possible to treat extended areas of the skin with
      accelerated electrons. Total skin electron beam radiation (TSEB) has been in use
      for several decades, and a number of technical modifications have been made with
      the goals of optimizing dose distribution and improving clinical outcome.
      Emerging evidence from recent studies suggests an association between TSEB
      techniques and efficacy in the treatment of MF. Based on this evidence, the
      European Organization for Research and Treatment of Cancer Cutaneous Lymphoma
      Project Group, in association with experts from radiotherapy centers in North
      America, has reached a consensus on acceptable methods and clinical indications
      for TSEB in the treatment of MF. The aims of this report are to enhance
      accessibility of this highly efficacious treatment modality to patients with MF
      and to provide a point of reference for further clinical research.

PMID- 12196746
TI  - Acquired elastotic hemangioma: A clinicopathologic variant of hemangioma.
AB  - BACKGROUND: In recent years, many new cutaneous vascular proliferations have been
      described. This is partly due to the current epidemic of AIDS, which has forced
      dermatopathologists to establish the diagnosis of the earliest patch-stage
      lesions of AIDS-related Kaposi's sarcoma and some of the recently described
      cutaneous vascular proliferations that may histopathologically mimic lesions of
      early Kaposi's sarcoma. OBJECTIVE: This article reports the clinical,
      histopathologic, and immunohistochemical findings in 6 cases of a
      clinicopathologic variant of cutaneous hemangioma, which we have named acquired
      elastotic hemangioma. METHODS: Six cases of acquired elastotic hemangioma were
      studied from clinical, histopathologic, and immunohistochemical standpoints. The
      histopathologic differential diagnosis with other similar cutaneous vascular
      proliferations is discussed. RESULTS: Acquired elastotic hemangioma appears on
      the sun-damaged skin of the dorsal aspect of the forearms or on the lateral
      aspects of the neck of middle-aged or elderly women. Clinically, lesions present
      as solitary erythematous plaques with variable morphology and in only some cases
      have a clearly angiomatous appearance. On histopathologic examination, acquired
      elastotic hemangioma is characterized by a band-like proliferation of capillary
      blood vessels involving the superficial dermis and arranged horizontally parallel
      to the epidermis. CONCLUSION: Acquired elastotic hemangioma is a distinctive
      clinicopathologic variant of hemangioma that should be differentiated from other
      cutaneous vascular proliferations. On histopathologic examination, it is
      characterized by capillary proliferation involving the dermis.

PMID- 12196747
TI  - A randomized clinical trial of 5% topical minoxidil versus 2% topical minoxidil
      and placebo in the treatment of androgenetic alopecia in men.
AB  - BACKGROUND: Topical minoxidil solution 2% stimulates new hair growth and helps
      stop the loss of hair in individuals with androgenetic alopecia (AGA). Results
      can be variable, and historical experience suggests that higher concentrations of
      topical minoxidil may enhance efficacy. OBJECTIVE: The purpose of this 48-week,
      double-blind, placebo-controlled, randomized, multicenter trial was to compare 5%
      topical minoxidil with 2% topical minoxidil and placebo in the treatment of men
      with AGA. METHODS: A total of 393 men (18-49 years old) with AGA applied 5%
      topical minoxidil solution (n = 157), 2% topical minoxidil solution (n = 158), or
      placebo (vehicle for 5% solution; n = 78) twice daily. Efficacy was evaluated by
      scalp target area hair counts and patient and investigator assessments of change
      in scalp coverage and benefit of treatment. RESULTS: After 48 weeks of therapy,
      5% topical minoxidil was significantly superior to 2% topical minoxidil and
      placebo in terms of change from baseline in nonvellus hair count, patient rating
      of scalp coverage and treatment benefit, and investigator rating of scalp
      coverage. Hair count data indicate that response to treatment occurred earlier
      with 5% compared with 2% topical minoxidil. Additionally, data from a patient
      questionnaire on quality of life, global benefit, hair growth, and hair styling
      demonstrated that 5% topical minoxidil helped improve patients' psychosocial
      perceptions of hair loss. An increased occurrence of pruritus and local
      irritation was observed with 5% topical minoxidil compared with 2% topical
      minoxidil. CONCLUSION: In men with AGA, 5% topical minoxidil was clearly superior
      to 2% topical minoxidil and placebo in increasing hair regrowth, and the
      magnitude of its effect was marked (45% more hair regrowth than 2% topical
      minoxidil at week 48). Men who used 5% topical minoxidil also had an earlier
      response to treatment than those who used 2% topical minoxidil. Psychosocial
      perceptions of hair loss in men with AGA were also improved. Topical minoxidil
      (5% and 2%) was well tolerated by the men in this trial without evidence of
      systemic effects.

PMID- 12196748
TI  - Pityriasis rubra pilaris in children.
AB  - BACKGROUND: Pityriasis rubra pilaris (PRP) is an uncommon dermatosis in children.
      Few long-term studies on the treatment and prognosis of PRP in children have been
      performed. OBJECTIVE: Our purpose was to retrospectively review the clinical
      course and treatment of all cases of PRP in children 19 years or younger who were
      seen at the Mayo Clinic. METHODS: The clinical courses of the 30 patients with
      PRP seen at the Mayo Clinic between 1975 and 1997 were reviewed. RESULTS: The
      most common presenting form of PRP in children is the type III juvenile form
      (Griffiths' criteria). Treatment ranged from topical steroids, tar, and
      ultraviolet B to systemic retinoids and methotrexate. The best response was
      obtained with isotretinoin; 5 of 6 patients showed 90% to 100% clearing within 6
      months of treatment. Follow-up information was obtained by questionnaire and was
      available for 83% of patients. Overall, 43% had 90% to 100% resolution of their
      disease, 23% had a moderate response (30%-90% improvement), and 17% had a poor
      response (<30% improvement). One patient reported spontaneous resolution.
      Seventeen percent of those who had total clearing had recurrence of PRP within 1
      year. CONCLUSION: PRP in children is a noninherited dermatosis with no sex
      predilection, occurring mainly in the type III classic juvenile form. Retinoids
      should be considered as first-line treatment for PRP. Recurrence rate, previously
      thought to be rare, was about 17% in our population.

PMID- 12196749
TI  - Imiquimod 5% cream for the treatment of superficial basal cell carcinoma: a
      double-blind, randomized, vehicle-controlled study.
AB  - BACKGROUND: Imiquimod 5% cream may provide an effective nonsurgical treatment for
      superficial basal cell carcinoma (sBCC) based on results of previous studies.
      OBJECTIVE: The objective of this phase II dose-response study was to explore
      various dosing regimens using imiquimod 5% cream for sBCC to find the most
      effective frequency of dosing with tolerable side effects. METHODS: Patients (n =
      128) were dosed twice daily, once daily, 5 times a week, or 3 times a week in
      this 12-week, randomized, double-blind, vehicle-controlled study. At 6 weeks
      after treatment, the entire tumor area was clinically evaluated, excised, and
      examined exhaustively for histologic evidence of residual sBCC. RESULTS: Complete
      response rates were 100% (10/10), 87.1% (27/31), 80.8% (21/26), and 51.7% (15/29)
      for patients in the twice daily, once daily, 5 times a week, and 3 times a week
      imiquimod groups, respectively, and 18.8% (6/32) in the vehicle group.
      CONCLUSION: Imiquimod 5% cream was effective in the treatment of sBCC. Daily or 5
      times a week dosing for 12 weeks demonstrated high efficacy results with
      acceptable safety profiles.

PMID- 12196750
TI  - Efficacy of a low-dose oral contraceptive containing 20 microg of ethinyl
      estradiol and 100 microg of levonorgestrel for the treatment of moderate acne: A
      randomized, placebo-controlled trial.
AB  - BACKGROUND: Acne is a multifactorial disease in which androgens appear to play an
      important role. A low-dose oral contraceptive containing 20 microg of ethinyl
      estradiol and 100 microg of levonorgestrel (EE/LNG) has been shown to improve
      biochemical markers of androgenicity. Lowering bioavailable androgens may improve
      acne. OBJECTIVE: The aim of this study was to evaluate the efficacy and safety of
      a low-dose oral contraceptive containing 20 microg of EE and 100 microg of LNG
      for the treatment of moderate acne. METHODS: In a randomized, double-blind,
      placebo-controlled clinical trial, healthy female subjects (n = 371; >/=14 years
      old) with regular menstrual cycles and moderate facial acne were randomly
      assigned to receive EE/LNG or placebo for 6 cycles of 28 days. Acne lesion counts
      and clinician global assessment were performed at the end of each cycle. Patient
      self-assessments were collected and biochemical markers of androgenicity were
      also measured. RESULTS: At the end of the study, the number of inflammatory and
      total lesions was significantly lower with EE/LNG compared with placebo (P <.05).
      Patients in the EE/LNG group also had significantly better scores for clinician
      global and patient self-assessments than those in the placebo group (P <.05).
      Biochemical markers of androgenicity improved during EE/LNG treatment compared
      with placebo and baseline values. CONCLUSION: A low-dose oral contraceptive
      containing EE/LNG is effective and safe for the treatment of moderate acne.

PMID- 12196751
TI  - Medium-dose ultraviolet A1 therapy for pityriasis lichenoides et varioliformis
      acuta and pityriasis lichenoides chronica.
AB  - BACKGROUND: Ultraviolet A1 (340-400 nm) was found to be effective in the
      treatment of cutaneous T-cell-mediated diseases. OBJECTIVE: The purpose of the
      present study was to assess the efficacy of UVA1 phototherapy for pityriasis
      lichenoides et varioliformis acuta (PLEVA) and pityriasis lichenoides chronica
      (PLC). METHODS: Eight patients (3 with PLEVA and 5 with PLC) received 60 J/cm(2)
      UVA1 daily until remission. Four patients also had lesions inaccessible to UVA1
      that were used as control lesions. Immunocytologic studies of skin infiltrates
      and circulating T cells were done. RESULTS: Six patients showed complete clinical
      and histologic recovery. Two patients with PLC had a partial improvement.
      Unirradiated control lesions never improved. Serious short-term adverse effects
      were not encountered. No effects on circulating lymphocytes were reported.
      CONCLUSION: UVA1 therapy is an effective and well-tolerated treatment for PLEVA
      and PLC. The therapeutic activity seems to be related to direct effects on
      cutaneous inflammatory infiltrates because the lesions in nonexposed cutaneous
      areas did not respond.

PMID- 12196752
TI  - Itraconazole therapy for white piedra affecting scalp hair.
AB  - BACKGROUND: Treatment of white piedra remains an area of therapeutic frustration.
      Several topical and systemic antifungal agents have failed to eradicate the
      fungus and prevent disease recurrence. Itraconazole is a safe and effective
      systemic antifungal agent for various superficial and deep mycotic infections of
      the skin and hair. In vitro studies have shown significant antifungal activity
      against Trichosporon beigelii. OBJECTIVE: Our study was intended to assess the
      efficacy of itraconazole in the treatment of uncomplicated white piedra affecting
      the scalp hair. METHODS: The study was designed as an open trial involving 12
      female patients with white piedra of the scalp hair. They were administered oral
      itraconazole 100 mg once daily until culture negativity was achieved; they were
      then followed up for 3 months. RESULTS: Eleven patients (91.67%) showed disease
      remission after 8 weeks of treatment. One patient (8.33%) showed no improvement,
      and the disease recurred in 2 patients (16.67%) after completion of therapy. No
      significant side effects were noted.

PMID- 12196753
TI  - Prognostic factors for life expectancy in nonagenarians with nonmelanoma skin
      cancer: implications for selecting surgical candidates.
AB  - BACKGROUND: Controversy exists over surgical intervention for nonmelanoma skin
      cancer in the very elderly. OBJECTIVE: We sought to define variables that are
      prognostic for survival in the elderly after surgery for skin cancer. METHODS: We
      reviewed 99 charts of nonagenarians who had Mohs micrographic surgery for
      nonmelanoma skin cancer and recorded data on comorbid conditions and date of
      death. Comorbid conditions were quantified by the Charlson index. RESULTS:
      Patients with Charlson scores of zero (no comorbidities) had a statistically
      significant longer survival than patients with Charlson scores of >/=3 (multiple
      comorbidities). Women survived longer than men at both 1 and 5 years. No patient
      died within 30 days of operation. CONCLUSION: Charlson scores of >/=3 in
      nonagenarians predict shorter survival. Although this parameter may predict
      shorter survival when skin cancer surgery is considered in a cohort of elderly
      patients, it remains difficult to predict accurately the survival of individual
      patients with scores >/=3.

PMID- 12196754
TI  - Warty dyskeratoma--"follicular dyskeratoma": analysis of clinicopathologic
      features of a distinctive follicular adnexal neoplasm.
AB  - BACKGROUND: The clinicopathologic spectrum of warty dyskeratoma (WD) is not well
      characterized and the pathogenesis of this unusual lesion is still unclear.
      OBJECTIVE: We reviewed the clinical and histopathologic spectrum of WD and
      investigated a possible involvement of human papillomavirus (HPV) infection in
      onset of this lesion. METHODS: A total of 46 cases of WD were analyzed clinically
      and histopathologically. Polymerase chain reaction (PCR) analysis for HPV-DNA was
      performed in 13 lesions of WD. RESULTS: A total of 46 lesions of WD from 45
      patients (M/F ratio, 1:1.8; mean age 59.8 years, median 61 years, age range 3-88
      years) presented as solitary papules or small nodules on the head and neck (32
      cases), trunk (9 cases), lower extremities (4 cases), and upper extremities (1
      case). One patient had 2 lesions. No patient had clinical signs of Darier's or
      Grover's disease. Histopathologically on scanning magnification, lesions showed
      mainly 3 architectural patterns, namely, cup-shaped (29 cases), cystic (6 cases),
      and nodular (2 cases). In 9 cases, a combination of two of these morphologic
      patterns was observed. Characteristically, the epithelial component in all WDs
      displayed foci of acantholytic dyskeratosis. Variable features suggestive of
      follicular differentiation toward the infundibular portion of a normal hair
      follicle were also observed, including a focal contiguity to pilosebaceous units
      in most cases (63%), and the presence of small infundibular cystic structures in
      a subset of lesions (46%). The majority of lesions (83%) also revealed a
      hyalinized or fibrous stroma with intrastromal clefts. PCR analysis for HPV-DNA
      performed in 13 cases inclusive of all representative architectural patterns was
      negative. CONCLUSION: We conclude that WD shows a wider spectrum of morphologic
      features than previously recognized. Despite some histopathologic similarities to
      viral warts, WD is not a manifestation of HPV infection. On the other hand, the
      majority of these lesions display overall histopathologic features consistent
      with a follicular adnexal neoplasm. On the basis of this finding, we propose the
      alternative term follicular dyskeratoma to better reflect the distinctive
      features of this peculiar lesion.

PMID- 12196755
TI  - Eccrine angiomatous hamartoma.
AB  - Four patients with eccrine angiomatous hamartoma are described. Blue-purple
      color, enlarging size, location on an extremity, pain, and hypertrichosis were
      common features and aided differentiation from other vascular anomalies and
      hamartomas of childhood. None of our patients experienced lesional hyperhidrosis,
      and simple excision alleviated pain.

PMID- 12196756
TI  - Medical pearl: DHA application for camouflaging segmental vitiligo and piebald
      lesions.

PMID- 12196757
TI  - Surgical pearl: punch technique to improve granulation over exposed tendons in
      chronic wounds.

PMID- 12196758
TI  - Congenital Spitz nevus clinically mimicking melanoma.
AB  - The differentiation between atypical variants of Spitz nevus and melanoma is
      often difficult given the many clinical and histopathologic similarities between
      the two. We report a case of an infant with a congenital scalp lesion exhibiting
      clinical features of melanoma, including variegation and regression of
      pigmentation and a rapidly changing appearance. Histologic examination of the
      excised lesion revealed a benign congenital Spitz nevus. This case emphasizes the
      need for clinical and histologic correlation in determining the benign or
      malignant nature of atypical pigmented lesions in infants.

PMID- 12196759
TI  - Extensive Riga-Fede disease of the lip and tongue.
AB  - Riga-Fede disease presents in early infancy and is characterized by firm,
      verrucous plaques arising on the oral mucosal surfaces. These histologically
      benign lesions occur as a result of repetitive trauma of the oral mucosal
      surfaces by the teeth. Early recognition of this entity is important, because it
      may be the presenting sign of an underlying neurologic disorder. We report the
      case of a 10-month-old boy with extensive Riga-Fede disease involving the lip and
      tongue that prompted a diagnosis of congenital autonomic dysfunction with
      universal pain loss.

PMID- 12196760
TI  - Acrokeratoelastoidosis.
AB  - Acrokeratoelastoidosis is a genodermatosis characterized by firm papules or
      plaques on the sides of the hands and feet. Although poorly understood, the
      lesions may result from an abnormality in the secretion or excretion of elastic
      material by fibroblasts in the dermis. In this report, we will present a patient
      with this rare condition and review the clinical and histopathologic features,
      cause, and differential diagnosis.

PMID- 12196761
TI  - Heparin-induced thrombocytopenia: a complication in extracorporeal
      photochemotherapy (photopheresis).

PMID- 12196762
TI  - Photoeruption in a patient treated with capecitabine (Xeloda) for metastatic
      breast cancer.

PMID- 12196763
TI  - Friction hypermelanosis: other variants.

PMID- 12196764
TI  - Safety considerations in the treatment of dermatophytosis.

PMID- 12196765
TI  - Treating keratosis pilaris.

PMID- 12196766
TI  - N-docosanol (Abreva) for herpes labialis: problems and questions.

PMID- 12196767
TI  - The yield of lower endoscopy in patients with constipation: survey of a
      university hospital, a public county hospital, and a Veterans Administration
      medical center.
AB  - BACKGROUND: The role of endoscopy in the evaluation of constipation is
      controversial. The aim of this study was to clarify the yield of lower endoscopy
      in patients with constipation. METHODS: Endoscopic databases from 3 diverse
      hospitals were searched for procedures with constipation as an indication.
      Detection of neoplasia was the main outcome of interest. RESULTS: Among 19,764
      sigmoidoscopies or colonoscopies, constipation was a procedure indication for 563
      patients (mean age 61 [16] years, 52% women); 58% had procedure indications in
      addition to constipation. Colorectal cancer was diagnosed in 8 (1.4%), adenomas
      in 82 (14.6%), and advanced lesions (cancer or adenoma with malignancy, high
      grade dysplasia, villous features, or size > or = 10 mm) in 24 (4.3%). In the 358
      patients who underwent colonoscopy, cancer was detected in 1.7%, adenomas in
      19.6%, and advanced lesions in 5.9%. Two patients with cancer were less than 50
      years of age. In as many as 6 patients with cancer, the tumor may have caused
      partial obstruction. CONCLUSIONS: The range of neoplasia in patients with
      constipation evaluated with lower endoscopy was comparable with what would be
      expected in asymptomatic subjects undergoing colorectal cancer screening.
      Although chronic constipation alone may not be an appropriate indication for
      lower endoscopy, age-appropriate colorectal cancer screening should be pursued
      when patients with constipation seek medical care.

PMID- 12196768
TI  - Total colonic dye-spray increases the detection of diminutive adenomas during
      routine colonoscopy: a randomized controlled trial.
AB  - BACKGROUND: Small adenomas may be missed during colonoscopy, but chromoscopy has
      been reported to enhance detection. The aim of this randomized-controlled trial
      was to determine the effect of total colonic dye spray on adenoma detection
      during routine colonoscopy. METHODS: Consecutive outpatients undergoing routine
      colonoscopy were randomized to a dye-spray group (0.1% indigo carmine used to
      coat the entire colon during withdrawal from the cecum) or control group (no
      dye). RESULTS: Two hundred fifty-nine patients were randomized, 124 to the dye
      spray and 135 to the control group; demographics, indication for colonoscopy, and
      quality of the preparation were similar between the groups. Extubation from the
      cecum took a median of 9:05 minutes (range: 2:48-24:44 min) in the dye-spray
      group versus 4:52 minutes (range: 1:42-15:21 min) in the control group (p <
      0.0001). The proportion of patients with at least 1 adenoma and the total number
      of adenomas were not different between groups. However, in the dye-spray group
      significantly more diminutive adenomas (<5 mm) were detected proximal to the
      sigmoid colon (p = 0.026) and more patients were identified with 3 or more
      adenomas (p = 0.002). More non-neoplastic polyps were detected throughout the
      colon in the dye-spray group (p = 0.003). There were no complications.
      CONCLUSIONS: Dye-spray increases the detection of small adenomas in the proximal
      colon and patients with multiple adenomas, but long-term outcomes should be
      studied to determine the clinical value of these findings.

PMID- 12196769
TI  - Tattoo of colonic neoplasms in 113 patients with a new sterile carbon compound.
AB  - BACKGROUND: Endoscopic marking of intestinal lesions is essential when difficulty
      is anticipated with subsequent localization during surgical resection or
      postpolypectomy surveillance. The most commonly used indelible marker has been
      India ink, which must be diluted and sterilized, a cumbersome process. SPOT, a
      prepackaged, sterile Food and Drug Administration-approved formulation of pure
      carbon particles in suspension, eliminates the need for preinjection preparation.
      METHODS: Ten patients with colonic polyps deemed endoscopically unresectable or
      malignant-appearing had the area surrounding the lesions injected with SPOT and
      subsequently underwent surgical resection. An additional 103 patients underwent
      colonoscopic injection with SPOT and were followed endoscopically or underwent
      surgery at another hospital. RESULTS: The SPOT injection sites were visible to
      the surgeons in all 10 cases. On histopathologic evaluation, none of the
      resection specimens exhibited necrosis or abscess formation. In total, there were
      118 SPOT injections in 113 patients; none had fever, abdominal pain, or any other
      signs or symptoms of inflammation develop. In the nonoperated group, 42 patients
      subsequently underwent colonoscopies at our institution, and in all cases stains
      were readily identifiable at the injection sites. CONCLUSIONS: SPOT is a safe and
      effective marker for use at colonoscopy when surgical resection is anticipated.
      It is also useful for endoscopic follow-up of patients who have not undergone
      surgery.

PMID- 12196770
TI  - The role of colonoscopy in the diagnosis of appendicitis in patients with
      atypical presentations.
AB  - BACKGROUND: Acute appendicitis is one of the most common causes of acute abdomen.
      Despite recent advances in radiologic imaging, the diagnosis of acute
      appendicitis may be difficult on occasion. The aims of this study were to
      describe the colonoscopic features of appendicitis and to determine whether
      colonoscopy can be used as an adjunct for the diagnosis of appendicitis in
      patients with atypical presentations. METHODS: The colonoscopic findings in 21
      patients (14 men, 7 women; average age 55 years) with a colonoscopic or
      histopathologic diagnosis of appendicitis were analyzed retrospectively.
      Colonoscopy was performed because diagnoses suggested by CT were other than acute
      appendicitis (11 patients), and/or the presenting clinical features were atypical
      for acute appendicitis with the duration of symptoms being 10 days or longer (17
      patients). RESULTS: The colonoscopic diagnosis was acute appendicitis for all 21
      patients. Seventeen underwent appendectomy, the diagnosis being verified in all
      cases. Of the 4 patients whose symptoms improved without appendectomy, 3 were
      considered to have acute appendicitis because pus was seen to drain from the
      appendiceal orifice at colonoscopy. A definite diagnosis could not be made in the
      remaining 1 patient. Therefore, the diagnosis of appendicitis was considered
      confirmed in 20 of 21 patients. Colonoscopic findings in these 20 patients
      included hyperemia (15) and bulging (18) at the appendiceal orifice area with
      surrounding mucosal edema (19), and drainage of pus from the appendiceal orifice
      (7). CONCLUSION: Colonoscopy may be useful in the diagnosis of appendicitis when
      the clinical presentation is atypical for appendicitis and/or imaging studies are
      nondiagnostic.

PMID- 12196771
TI  - Capsule endoscopy in the evaluation of patients with suspected small intestinal
      bleeding: Results of a pilot study.
AB  - BACKGROUND: A video capsule has been developed to acquire photographic images of
      the small intestine during normal peristaltic motion. METHODS: Patients between
      21 and 80 years of age referred for enteroscopy because of obscure GI bleeding
      were offered entry into a trial in which they would undergo both capsule
      endoscopy and subsequent push enteroscopy. Results of capsule examinations were
      compared with push enteroscopy findings. Capsule endoscopy was performed with the
      Given M2A video capsule system. RESULTS: Twenty-one patients (12 women, 9 men,
      average age 61 years) were enrolled, all of whom completed the study. A bleeding
      site was found in 11 of 20 patients during capsule endoscopy. No additional
      intestinal diagnoses were made by enteroscopy. The yield of push enteroscopy in
      the evaluation of obscure bleeding was 30% (6/20), the yield of capsule endoscopy
      55% (11/20). This difference did not reach statistical significance (p = 0.0625).
      Capsule endoscopy found a distal source of bleeding in 5 of 14 patients who had
      normal push enteroscopic examinations. Patients preferred capsule endoscopy to
      enteroscopy. CONCLUSIONS: This pilot study demonstrates that capsule endoscopy
      provides excellent visualization of the small intestine, is well tolerated by
      patients, and is safe. Capsule endoscopy identified small intestinal bleeding
      sites beyond the range of push enteroscopy.

PMID- 12196772
TI  - Comparison of EUS and magnifying colonoscopy for assessment of small colorectal
      cancers.
AB  - BACKGROUND: Prediction of invasion depth and lymph node metastasis is mandatory
      when local treatment is considered for small colorectal cancer. The aim of this
      study was to compare the accuracy of EUS with a catheter probe (probe-EUS) and
      magnifying colonoscopy for prediction of invasion depth and lymph node metastasis
      for small colorectal cancer. METHODS: Small colorectal cancers were imaged by
      both probe-EUS and magnifying colonoscopy. Invasion depth by probe-EUS was
      determined by the presence or absence of distortion of the third sonographic
      layer. Findings by magnifying colonoscopy were divided into regular, distorted,
      and amorphous patterns. Histopathologically, depth of invasion was classified as
      intramucosa/slight or deep invasion. Findings by probe-EUS and magnifying
      colonoscopy were compared with respect to deep invasion and lymph node
      metastasis. RESULTS: There were 22 small colorectal cancers with
      intramucosa/slight invasion and 28 with deep invasion. Four of 30 cancers had
      associated lymph node metastasis. Accuracy for depth of invasion was 91.8% for
      probe-EUS and 63.3% in magnifying colonoscopy, the difference being statistically
      significant (p = 0.0013). Negative predictive value of probe-EUS for deep
      invasion was higher than that for magnifying colonoscopy (respectively, 90.9% vs.
      54.1%) in the population studied (prevalence deep invasion 56%). The accuracy for
      lymph node metastasis was 24.1% for probe-EUS and 72.4% for magnifying
      colonoscopy, the difference being statistically significant (p < 0.001). Positive
      predictive value for lymph node metastasis was higher when the amorphous pattern
      was noted by magnifying colonoscopy compared with the positive predictive value
      for deep invasion by probe-EUS (respectively, 33.3% vs. 8.7%) in the population
      studied (prevalence lymph node metastasis 13.3%). CONCLUSIONS: Probe-EUS is
      superior to magnifying colonoscopy for determination of invasion depth in small
      colorectal cancer. Magnifying colonoscopy may be predictive of lymph node
      metastasis, thereby suggesting that the procedures provide complementary
      information with respect to the decision for local versus surgical therapy.

PMID- 12196774
TI  - Peroral cholangioscopic treatment of hepatolithiasis: Long-term results.
AB  - BACKGROUND: Peroral cholangioscopic lithotomy is an effective treatment for
      extrahepatic bile duct stones. However, an evaluation of the usefulness and long
      term results of peroral cholangioscopic lithotomy for hepatolithiasis has not
      been reported. The aim of this study was to evaluate the usefulness and long-term
      results of peroral cholangioscopic lithotomy for hepatolithiasis. METHODS: From
      August 1987 to July 1998, 36 consecutive patients underwent peroral
      cholangioscopic lithotomy for hepatolithiasis; 34 were followed for a mean of 93
      months (range, 14 to 164 months). RESULTS: The rate of complete stone removal was
      64%; the morbidity rate was 2.8%. The recurrence rate for patients in whom stones
      were completely removed was 21.7%. Two patients (5.9%) had cholangiocarcinoma
      develop during follow-up. CONCLUSION: Although incomplete stone removal and
      recurrence are common, peroral cholangioscopic lithotomy is a sufficiently safe
      and effective method for the treatment of hepatolithiasis.

PMID- 12196773
TI  - Biliary decompression by nasobiliary catheter or biliary stent in acute
      suppurative cholangitis: a prospective randomized trial.
AB  - BACKGROUND: Endoscopic drainage has replaced emergent surgery for biliary
      decompression in patients with acute cholangitis. The aim of this study was to
      prospectively compare the efficacy of the nasobiliary catheter and indwelling
      stent as temporary measures for biliary decompression in acute suppurative
      cholangitis caused by bile duct stones. METHODS: Over a 60-month period, 79
      patients with acute cholangitis who required emergent endoscopic drainage were
      recruited. Indications for urgent drainage included any one of the following:
      temperature greater than 39 degrees C, septic shock with systolic blood pressure
      less than 90 mm Hg, increasing abdominal pain, and impaired level of
      consciousness. Patients who had previously undergone sphincterotomy or had
      coexisting intrahepatic duct stones were excluded. After successful bile duct
      cannulation, patients were randomized to receive either a nasobiliary catheter or
      indwelling stent without sphincterotomy for biliary decompression. Outcome
      measures included procedure time, complications, clinical response, and patient
      discomfort (scored with a 10-cm, unscaled visual analog score). RESULTS: Of the
      79 patients, 5 were excluded because of previous sphincterotomy and intrahepatic
      duct stones, 40 were randomized to receive a nasobiliary catheter (NBC group),
      and 34 to receive indwelling stent (stent group). Demographic data were similar
      between the groups. All procedures were successful in the NBC group; there was
      one failure in the stent group. The mean (SD) procedure time was similar (NBC
      group 14.0 [9.3] minutes vs. stent group 11.4 [7.2] min). There were 2 ERCP
      related complications in the NBC group. Four patients pulled out the nasobiliary
      catheter and one catheter became kinked. One stent occluded. There was a
      significantly lower mean (SD) patient discomfort score on day 1 after the
      procedure in the stent group (stent group 1.8 [2.6] vs. NBC group 3.9 [2.7]; p =
      0.02 t test). The overall mortality rate was 6.8% (2.5% NBC group vs. 12% stent
      group). CONCLUSION: Endoscopic biliary decompression by nasobiliary catheter or
      indwelling stent was equally effective for patients with acute suppurative
      cholangitis caused by bile duct stones. The indwelling stent was associated with
      less postprocedure discomfort and avoided the potential problem of inadvertent
      removal of the nasobiliary catheter.

PMID- 12196775
TI  - Evaluation of indeterminate bile duct strictures by intraductal US.
AB  - BACKGROUND: Cholangiography and tissue sampling (brush cytology, biopsy) are the
      standard nonsurgical techniques for determining whether a bile duct stricture is
      benign or malignant. The aim of this study was to determine whether intraductal
      US is of assistance in distinguishing benign from malignant biliary strictures.
      METHODS: A retrospective review was undertaken of 30 patients with indeterminate
      bile duct strictures who underwent ERCP and tissue sampling from September 1999
      to November 2000. A 20 MHz over-the-guidewire intraductal US catheter probe was
      used during ERCP for further examination of the strictures. Final diagnoses of
      malignant strictures (18 patients) were confirmed histopathologically;
      confirmation of benign stricture (12 patients) was based on negative tissue
      sampling plus extended clinical follow-up. RESULTS: Based on retrospective
      blinded review, the diagnosis by ERCP was correct in 67% of patients, by tissue
      sampling in 68%, by combined ERCP/tissue sampling in 67%, and by intraductal US
      in 90% (p = 0.04 vs. ERCP/tissue sampling) of cases. No complication of
      intraductal US or ERCP was recorded. CONCLUSIONS: Intraductal US is safe and can
      improve on the ability at ERCP to distinguish benign from malignant biliary
      strictures.

PMID- 12196776
TI  - Endoscopic cystenterostomy of nonbulging pancreatic fluid collections.
AB  - BACKGROUND: A prerequisite for endoscopic drainage of pancreatic fluid
      collections without EUS is the presence of a visible bulge in the GI wall. Our
      experience with endoscopic cystostomy of nonbulging pancreatic fluid collections
      is described. METHODS: Thirty-three patients underwent 34 endoscopic attempts at
      transmural drainage of nonbulging pancreatic fluid collections over a 2-year
      period. The etiology of the nonbulging pancreatic fluid collections was chronic
      pancreatitis in 26 cases and acute pancreatitis in 7. Indications for drainage
      included one or more of the following: abdominal pain, infection, biliary
      obstruction, and external fistula. The diameter of the collections ranged from 20
      to 160 mm (median 52 mm). RESULTS: Thirty-two of 34 drainage attempts were
      successful (94%). Eighteen cystostomies were performed under fluoroscopy alone
      and 14 by EUS together with fluoroscopy. Procedure-related complications occurred
      with 3 of 34 attempts (8%). Surgery was not required for treatment of the
      complications and there were no deaths from the procedure. Follow-up was
      available for 31 patients (median 21 months, range 9 to 40 months). One
      nonbulging pancreatic fluid collections recurred 7 months after drainage.
      CONCLUSIONS: Endoscopic cystenterostomy of nonbulging pancreatic collections is
      feasible, and the results of the procedure are similar to those of
      cystenterostomy for bulging collections.

PMID- 12196777
TI  - Long-term outcome after endoscopic mucosal resection in patients with esophageal
      squamous cell carcinoma invading the muscularis mucosae or deeper.
AB  - BACKGROUND: Endoscopic mucosal resection is recommended for squamous cell
      carcinoma of the esophagus confined to the lamina propria. However, endoscopic
      mucosal resection is often performed in patients with tumors that invade the
      muscularis mucosa or upper submucosa to minimize surgical invasiveness, despite
      the increased risk of lymph node metastasis. This study prospectively evaluated
      long-term outcome in such patients. METHODS: Twenty-six consecutive patients with
      squamous cell esophageal carcinoma invading the muscularis mucosa or submucosa
      who underwent endoscopic mucosal resection from June 1992 through March 2000
      (extended endoscopic mucosal resection group) were studied. As control group, 44
      consecutive patients with esophageal carcinoma invading the muscularis mucosae or
      upper third of the submucosa and no preoperative evidence of lymph node
      metastasis who underwent esophagectomy during the same period (surgical resection
      group) were studied. RESULTS: Overall survival rates at 5 years in the extended
      endoscopic mucosal resection group and surgical resection group were,
      respectively, 77.4% and 84.5%. There was no significant difference between
      survival distributions. Cause-specific survival rates at 5 years in extended
      endoscopic mucosal resection and surgical resection groups were, respectively,
      95.0% and 93.5%. Survival curves for the groups were similar. CONCLUSION:
      Although patients were not randomized to extended endoscopic mucosal resection or
      surgical resection in this study, the results suggest that endoscopic mucosal
      resection may be safe and effective for management of squamous cell esophageal
      carcinoma invading the muscularis mucosae or upper submucosa.

PMID- 12196778
TI  - Potential impact of preoperative EUS on esophageal cancer management and cost.
AB  - BACKGROUND: The purpose of this study was to determine the relative proportions
      of esophageal cancer stages in a group of patients referred for preoperative EUS,
      to determine the proportions of EUS stage 1 and 4 tumors that would not be
      treated with combined modality therapy, and to estimate the impact of the EUS
      diagnosis of these stages on costs. METHODS: A large national endoscopic database
      was reviewed retrospectively to identify cases of esophageal cancer in which
      there was a referral for preoperative staging with EUS. Data were analyzed as to
      demographics, histology and tumor stage by EUS according to the American Joint
      Commission for Cancer tumor node metastasis classification system for esophageal
      cancer. Cost estimates were based on Medicare reimbursement rates and published
      figures. RESULTS: Of 188 EUS procedures done for preoperative staging of
      esophageal cancer (82% men, mean age 66.5 years), the histopathologic types of
      cancer were: adenocarcinoma, 107; squamous cell carcinoma, 39; and unknown
      histology, 42. Numbers and proportions of patients by American Joint Commission
      for Cancer group stage based on 162 procedures for which complete staging
      information was available are as follows: Stage I, 23 patients (14%); Stage II,
      51 (31%); Stage III, 69 (43%); and Stage IV, 19 (12%). Therefore, for every 100
      patients staged before surgery with EUS (cost $63,420), 14 patients with Stage I
      disease would be spared neoadjuvant chemoradiotherapy (saving $122,192) and 12
      patients with Stage IV cancer would be spared surgery (saving $285,600) for an
      average cost savings of $3443 per patient. CONCLUSION: Preoperative staging of
      esophageal cancer with EUS identifies a significant proportion of patients (26%
      in this series) with stage I and IV tumors who may be spared combined modality
      therapy with an associated potential for cost savings.

PMID- 12196779
TI  - Clinical utility of EUS-guided fine-needle aspiration of mediastinal masses in
      the absence of known pulmonary malignancy.
AB  - BACKGROUND: Mediastinal masses represent a diagnostic challenge because of their
      proximity to numerous critical structures, difficulty of access for tissue
      sampling, and myriad potential pathologic etiologies. A large, single-center
      experience with EUS-guided fine-needle aspiration (EUS-FNA) in the diagnosis of
      non-lung cancer-related mediastinal masses is presented. METHODS: An EUS database
      was reviewed and all cases of mediastinal mass or lymphadenopathy encountered
      between 1994 and 1999 were included. Final diagnoses were determined by EUS-FNA
      cytology and clinical follow-up. RESULTS: Forty-nine patients were identified (27
      women, 22 men; mean age 58.1 years, range 30-89 years). A malignant process was
      diagnosed in 22 cases (45%) and a benign process in 24 (49%). The EUS-FNA
      specimen was nondiagnostic in 3 cases (6%). An accurate diagnosis was made in 46
      of the 49 patients (94%). No complication was noted. CONCLUSIONS: EUS-FNA is a
      minimally invasive technique that facilitates detection and tissue sampling of
      mediastinal masses. It is a safe procedure that can be performed with the patient
      under conscious sedation in an outpatient setting.

PMID- 12196780
TI  - Bacteria-free rinse water for endoscope disinfection.
AB  - BACKGROUND: Most breaches of endoscope disinfection result from inadequate manual
      cleaning or improper use of disinfectants. This is a description of how a quality
      assurance program identified rinse water as a source of bacterial contamination
      and how it facilitated the introduction of a novel means of delivering rinse
      water of high purity. METHODS: Between 1996 and 2001, weekly samples were
      obtained from accessory and suction channels of endoscopes as well as the
      internal chambers of automated washing machines. Samples were processed for
      routine bacterial and mycobacterial culture. RESULTS: Bacteria were isolated in
      8.7% of samples collected between 1996 and 1998. Of 36 positive samples, 20 (54%)
      were Pseudomonas sp. Analysis of rinse water from pipework downstream from
      filters demonstrated high growth of Pseudomonas sp, suggesting biofilm within
      piping was contaminating rinse water. A system of hot water flushing of pipework
      was developed that maintains a temperature above 60 degrees C for 60 minutes on a
      daily basis. This resulted in a consistently low level of bacterial
      contamination. CONCLUSION: This report demonstrates the value of a quality
      assurance program for endoscope disinfection and shows how rinse water may
      contaminate disinfected endoscopes. A system of hot water purging of the rinse
      water delivery system markedly reduces this contamination.

PMID- 12196781
TI  - Celiac disease for the endoscopist.

PMID- 12196782
TI  - Metastatic malignant melanoma.

PMID- 12196783
TI  - Aorto-esophageal fistula.

PMID- 12196784
TI  - Rectal ulcer mimicking mucosal prolapse syndrome.

PMID- 12196785
TI  - Recurrent sigmoid volvulus.

PMID- 12196786
TI  - Gastric polypoid signet ring cell carcinoma.

PMID- 12196787
TI  - Vanishing gastric tumor.

PMID- 12196788
TI  - An open pilot study of the effects of a human fibrin glue for endoscopic
      treatment of patients with acute bleeding from gastric varices.
AB  - BACKGROUND: Optimal treatment for gastric variceal bleeding remains to be
      determined. The use of conventional sclerosing agents is associated with high
      rates of recurrent bleeding. Other agents, such as cyanoacrylate, have
      significant complication rates and can damage endoscopic equipment. The risk of
      prior-associated disease has caused concern regarding the use of bovine thrombin.
      METHODS: Beriplast-P (human thrombin) forms a fibrin clot at the needle tip
      immediately upon injection through a double lumen needle. In 10 patients with
      gastric variceal bleeding, a median dose of 6 mL of Beriplast-P was injected into
      gastric varices. OBSERVATIONS: Immediate hemostasis was achieved in 7 of 10
      patients (70%) with a single injection. At a median follow-up of 8 months, there
      was no recorded episode of recurrent bleeding from gastric varices. CONCLUSIONS:
      These results suggest that Beriplast-P is useful in the treatment of gastric
      variceal bleeding. Refinements in the design of the injection needle may improve
      the efficacy of this novel therapy.

PMID- 12196789
TI  - Overtube-assisted ERCP in patients with altered gastric and esophageal anatomy.
AB  - INTRODUCTION: ERCP has been a significant advance in the diagnosis and treatment
      of pancreatic and biliary diseases. However, anatomic variations may prevent
      successful ERCP. METHODS: Advancement of a duodenoscope during ERCP was impeded
      in 4 patients by anatomic alterations of the esophagus and/or the stomach. The
      overtube, 80 cm length, was used to allow passage of a duodenoscope to the
      papilla. RESULTS: All overtube assisted ERCP procedures were completed
      successfully and included sphincterotomy (2), bile duct stone extraction (2), and
      placement of a metal expandable stent (1). CONCLUSION: Use of an overtube allows
      safe and successful passage of a duodenoscope in patients with anatomic
      alterations of the esophagus and/or the stomach.

PMID- 12196790
TI  - Use of a phased vector array US catheter for EUS.
AB  - BACKGROUND: Existing EUS catheter probes have limited depth of penetration and
      lack color flow and Doppler capabilities. This study prospectively assessed the
      feasibility and safety of using a phased vector array US catheter in the human GI
      tract. METHODS: Eleven patients underwent EUS with a steerable 9F phased vector
      array catheter. Images obtained with the catheter were compared with standard EUS
      images. RESULTS: The GI wall layers were equally well imaged with the catheter
      compared with standard echoendoscopes in 90% of the cases. Images of the liver,
      spleen, pancreatic parenchyma, and pancreatic duct were of equal quality and
      resolution with both techniques in the majority of patients. Some deeper
      structures and blood vessels were better visualized with the catheter. No
      complications were encountered. CONCLUSION: The steerable phased vector array US
      catheter is a safe device when used in the GI tract and offers images comparable
      with those obtained with a dedicated echoendoscope. Further studies are needed to
      determine the accuracy of tumor staging and clinical utility of this device.

PMID- 12196791
TI  - Dissolution of blood clots in the biliary ducts with a thrombolytic agent infused
      through nasobiliary catheter.

PMID- 12196792
TI  - Gastric pancreatic rest leading to pyogenic liver abscess.

PMID- 12196793
TI  - Intraductal mucinous papillary tumor and pyloric gland adenoma of the pancreas.

PMID- 12196794
TI  - Embryonal rhabdomyosarcoma in a 3-year-old child diagnosed at ERCP: case report
      and review.

PMID- 12196795
TI  - Iatrogenic Chilaiditi's syndrome.

PMID- 12196796
TI  - EUS-guided fine-needle aspiration of a renal mass: an alternative method for
      diagnosis of malignancy.

PMID- 12196797
TI  - Capsule endoscopy: the voyage is fantastic--will it change what we do?

PMID- 12196798
TI  - Small bowel endoscopy.

PMID- 12196799
TI  - Colonoscopy preparation: is there still room for senna?

PMID- 12196800
TI  - Difficulties encountered when using ERCP-based tissue sampling techniques to
      establish a diagnosis.

PMID- 12196801
TI  - Use of the intramural incision technique to retrieve a fractured biliary tube.

PMID- 12196802
TI  - Crossing the pond.

PMID- 12196803
TI  - Pursuing commitments.

PMID- 12196804
TI  - Regenerating nerves follow the road more traveled.

PMID- 12196805
TI  - Synaptic vesicle fusion and synaptotagmin: 2B or not 2B?

PMID- 12196806
TI  - Auditory space processing: here, there or everywhere?

PMID- 12196809
TI  - [CONSENSUS IN GASTROENTEROLOGY]

PMID- 12196810
TI  - [CLINICAL PATHOLOGICAL FEATURES AND SURVIVAL RATE FACTORS IN COMPLICATED PRIMARY
      GASTROINTESTINAL CANCERS]
AB  - This study evaluated 115 patients with complicated primary gastrointestinal
      cancers which underwent surgical resection at Belen Hospital, Trujillo, Per ,
      since 1966 to 1996, with the aim to determine their clinical-pathological
      features and to identify some prognostic factors that influenced five-year
      survival rate in those complicated with obstruction. Median age was 55 19 years
      (range, 4 to 91 years) and the male: femaleratio was of 1.5: 1. Abdominal pain
      was the most common symptom (100%). The most frequent complication was
      obstruction (72%), followed by perforation (17%) and massive haemorrage (11%).
      The gastric adenocarci noma was most frequently associated w th obstruction and
      massive haemorrage; whilst perforation ocurred meanly in small bowei neoplasms,
      especially in lymphomas. Five year survival rate in the total series was of 13%,
      and this was greater in those cases with obstruction. In patients with gastric
      outlet obstructive syndrome the tumor size (p<0.05) and macroscopic type (p<0.05)
      were factors related with the 5 - year - survival rate and in those with
      intestinal obstruction by colon cancer prognostic factors were the tumor size
      (p<0.05) and the clinical stage (p<0.05). We concluded that an early diagnosis in
      these patients is very important to define an opportune surgical treatment.

PMID- 12196811
TI  - [COMPARATIVE STUDY OF ALBENDAZOLE VERSUS NITROFURANS AND NITROIMIDAZOLES IN THE
      TREATMENT OF GIARDIASIS IN CHILDREN]
AB  - A prospective, longitudinal, comparative, open and aleatory study in Jaen
      (Cajamarca--Peru), was performed during November 1997 and January of 1998. The
      objective was to demonstrate the efficacy and tolerance of Albendazol compared
      with Metronidazol, Furazolidona, Tinidazol and Secnidazol in the treatment of
      giardiasis in children. 79 children with giardiasis, confirmed by parasitologic
      studies were evaluated and distributed randorrily for aleatory code in A,B,C,D
      and E groups. The A group received Albendazol (5 days), the B group Metronidazol
      (10 days), the C group Furazolidona (10 days), the D group Tinidazol (1 d a) and
      the E group Secnidazol (1 d a); Clinical controls and coproparasitologic studies
      were performad during and after the treatment. The cl nical efficacy in the
      groups was of 100% and the efficacy coproparas tological of 94.1% with
      Albendazol, 93.3% with Secnidazol and 100% with Metronidazol. Furazolidona and
      Tinidazol. The global efficacy was excel lent with Al bendazol in 64,7% and in
      less than 40% with the other drugs, being the biggest pharmacological tolerance
      with Albendazol (82,3%) and Secnidazol (80%). We conclude that Albendazol is as
      effective as Metronidazol, Furazolidona, Tinidazol and Secnidazol but faster in
      eradicating the Giardia lambila in children and with better tolerance that
      Metronidazol, Furazolidona and Tinidazol. We consider necessary to control
      Epidemiological factor associated, to eradicate the parasite permanently.

PMID- 12196812
TI  - [PREVALENCE OF HBsAg AND anti-HBs CARRIERS IN PREGNANT WOMEN WHO RESIDE IN
      DIFFERENT ENDEMIC AREAS LOCATED IN CENTRAL-SOUTHERN DEPARTAMENTS OF PERU]
AB  - The present study was performed to estimate the prevalence of HBV in pregnant
      women (mean age among groups 25,0 6,9) who live in areas of different endemicity,
      and located in the Departments of Lima, Junin, Apurimac, and Ayacucho in Peru.
      All studies were carried out using radioimmunological techniques. In the
      Instituto Materno Perinatal in Lima, located in a low endemical area, 2086
      pregnant women whose ages ranged between 14 and 44 years were evaluated (for
      laboratory tests) at their first prenatal examination. A prevalence of 9,38%
      (HbsAG+), 0,38% (Ratio), and 3,18% (HBsAg+, anti-HBsAg+) was found, corresponding
      to 107 HBsAg+ pregnant women whose treated newborn wouId prevent the HBV chronic
      infection of approximate 21 newborn each year. 63% HBsAg+ pregnant women were
      born in Departments other than Lima. In the Hospital de Apoyo La Merced, located
      in Chanchamayo, Junin, which is a medium endemic area, 217 pregnant women whose
      ages ranged between 14 and 48 years were evaluated. The prevalence found in this
      Hospital was of 1,38% (HBsAg+), 1,2% (Ratio), and 17,8% (HBsAg+, anti-HBs+). All
      positive HBsAg were negative for HBeAg. The projection of results corresponded to
      a total of 9 HbsAg+ pregnant women and 2 newborn preventive of chronic disease
      per year. In the Guillermo D az de la Vega Hospital in Abancay, Apurimac, located
      in a medium to high endemic area, 221 pregnant women whose ages ranged between 15
      and 46 years were evaluated. A prevalence of 1,36% (HBsAg+), 1,0% (Ratio), and
      36,16% (HBsAg+, anti-HBs+) was found. All positive HBsAg were negative for HBeAg.
      Projected results corresponded to a total of 37 HBsAg+ pregnant carriers and 7
      newborn preventive of chronic disease per year. The Hospital General de Huanta,
      in Ayacucho, located in a high endemicity area, presented a prevalence of 3,2%
      (HBsAg+), 1,9% (Ratio), and 76,2% (HBsAg+, anti-HBs+) from 126 pregnant women
      evaluated with ages between 15 and 48 years old. These results gave a total
      projection per year of 39 HBsAg+ pregnant women and 8 newborn preventive of
      chronic hepatic disease. Among a total of 4 positive HBsAg cases, 3 positive
      pregnant women were studied for HBeAg. All 3 were negative. These results
      establish the prevalence of HbsAg and antiHBs in pregnant women from different
      endemical areas with significant prevalence in the Departments of Ayacucho
      (Huanta), and Apurimac (Abancay). They also contribute towards the costbenefit
      analysis for the prevention of HBV chronic infection.

PMID- 12196813
TI  - [ULCERATIVE COLITIS: A 52 YEARS RETROSPECTIVE STUDY]
AB  - We present a retrospective study on 74 patients with inespecific chronic
      ulcerative colitis according to diagnostic criteria. The higher incidence was
      present in patients between 30 and 40 years old. The most frequent symptom was
      diarrhea (95%), abdominal pain (79%), rectal bleeding (87%), rectal tenesmus
      (50%), weight loss (36%), and fever (18%). In relation to the degree of severity,
      we found that 33,7% suffered mild symptoms, 46,6% had moderate symptoms, while
      17,7% suffered severe symptoms. The endoscopic findings were: 93,2% friability,
      90,5% hyperemia, and 84,4% granulatio. Mortality was of 6,7%. We concluded that
      this disease is rare in Peru. The related mortailty is low, symptoms are mostly
      moderate, and no association with cancer of colon was evidenced.

PMID- 12196814
TI  - [NUTRITIONAL CONSIDERATIONS AND MANAGEMENT OF SHORT BOWEL SYNDROME]
AB  - Few conditions pose as great a challenge, in terms of long term nutritional care,
      as short bowel syndrome (SBS). Despite the complexity of care which children with
      SBS require, the great improvement in the prognosis and outcome over the past few
      decades can be attributed, in great measure, to advancements in both parenteral
      and enteral nutrition support. Most children can maintain normal growth and
      development while intestinal adaptation occurs, and ultimately achieve
      independence from parenteral nutrition. This review focuses on the nutritional
      consequences of severe malabsorption clinical problems which influence
      nutritional status, and parenteral and enteral nutritional recommendations. The
      importance of aggressive and persistant efforts with enteral feeding as a primary
      therapy to enhance bowel adaptation and tominimize complications is emphasized.

PMID- 12196815
TI  - [HEPATIC AMYLOIDIOSIS: REPORT OF ONE CASE]
AB  - We present a case of a 62-year old patient with systemic amyloidosis. The
      conclusive diagnosis was made by liver biopsy. The most important features of the
      disease, diagnosis, treatment, and prognosis were reviewed. We emphasize the
      importance of clinical acumen for diagnosis.

PMID- 12196816
TI  - [DUCLOS LHERMITE DISEASE: REPORT OF ONE CASE AND LITERATURE REVIEW]
AB  - Lhermitte-Duclos disease (also known as dysplastic gangliocytoma of the
      cerebellum) is an unusual disorder, is now known to occur in young patients as a
      manifestation of Cowden disease. We report the case of a young male, 31 years
      old, with this unusual disease who was sugically treated for the neurologic
      neoplasia. And submitted to colonoscopic polypectomy for the hamartomatous
      colonic polyps.

PMID- 12196817
TI  - [Characteristics of polymorphism of 129th amino acid in PRNP among Han and Uighur
      Chinese].
AB  - BACKGROUND: An amino acid polymorphism for Met to Val has been identified at PrP
      codon 129 from different human races. In this study,the characteristics of
      polymorphism of PRNP 129th amino acid in Han and Uighur Chinese have been
      investigated. METHODS: Human DNAs were extracted from peripheral lymphocytes and
      PrP gene fragments were amplified with a specific PCR protocol. The distribution
      of 129th amino acid in PRNP was determined by a PCR-RFLP and the results were
      analyzed with software SAS for Windows 6.12. RESULTS: The frequencies of the
      allele 129 Met and 129 Val were 97.0% and 3.0% in Han Chinese, whereas 91.4% and
      8.6% in Uighur Chinese. The frequency of 129 M/M phenotypes in Han Chinese was
      significantly higher than that in Uighur Chinese (P=0.0490). Comparing the
      phenotype distributions of codon 129 of Han Chinese with that of Japanese and
      Caucasian, there was significant difference with Caucasian (P=0.0005),but there
      was no difference with Japanese (P=0.5040). CONCLUSIONS: The polymorphism of
      129th amino acid in PRNP of Han Chinese is similar to Japanese, but different
      from Uighur Chinese.

PMID- 12196819
TI  - [Association between NS5A gene sequence and response to interferon therapy in
      chronic hepatitis C patients in Shanghai].
AB  - BACKGROUND: To elucidate relationship between amino acid sequence of non
      structural protein 5A (NS5A) and outcome of HCV (1 b) patients after interferon
      (IFNa) therapy. METHODS: Sera of 24 patients were collected before, during and
      after IFNa therapy. Pretreatment RNA levels and the sequences of HCV NS5A
      interferon sensitivity determining region (ISDR) were determined. NS5A full
      length sequences of 5 HCV isolates from 3 patients with different response types
      were also analyzed. Phylogenetic tree analysis and protein secondary structure
      prediction were undertaken. RESULTS: Pretreatment RNA levels of sustained
      response group were significantly lower than that of non-response group and
      relapse group (4.50X104 copies/ml versus 1.82X107 copies/ml, P < 0.01).ISDR
      sequences of NS5A from pretreatment sera were compared with HCV-J strain
      (prototype). Thirteen of 24 isolates were wild type,11 of 24 were intermediate
      type and none of them was mutant type. 3 of 6 sustained responders were infected
      with wild-type isolates, the rest with intermediate type isolates. Phylogenetic
      tree based on NS5A full-length sequences classified 5 isolates with 3 different
      response types into 3 groups. Non-response isolates belonged to the same group as
      HCV-J. Secondary structure prediction of 5 isolates revealed significant
      differences existing in 2 255- 2 289. This region was partly overlapped with PKR
      binding domain. CONCLUSIONS: Low HCV RNA levels in serum are associated with
      favorable outcome of IFNa therapy. ISDR sequence alone could not predict outcome
      of IFN treatment. Combination of determination of HCV RNA levels in serum with
      sequence analysis of PKR-binding domain may be helpful in predicting the efficacy
      of IFN therapy.

PMID- 12196818
TI  - [Expression of the main structural antigen VP6 of human rotavirus by recombinant
      adenovirus and immune responses induced in vivo].
AB  - BACKGROUND: Constructing replication defective recombinant adenovirus vector
      expressing the group specific antigen VP6 of human rotavirus and studying the
      immune responses induced in vivo. METHODS: The cDNA of full length VP6 was
      inserted into the adenovirus vector pShuttle-CMV, and recombinant adenovirus
      genome DNA was obtained through homological recombination in E.coli,then the
      recombinant adenovirus was gained after transfecting 293 cell line with the
      genome DNA. Gene integration of VP6 in resultant adenovirus was confirmed by PCR
      and Southern blot, respectively gene expression was confirmed in 293 cells by
      Western blot. BALB/c mice were immunized intranasally(inl)and orally(ora),
      respectively, to test the immunization effects of the adenovirus. RESULTS:
      Recombinant adenovirus named rvAd-VP6 was obtained. The cDNA of VP6 was
      integrated in the adenovirus and was able to be expressed in 293 cells stably.
      The systemic immune responses to rotavirus VP6 could be induced effectively in
      both oral and intranasal group, the titer of serum IgG antibody in the two group
      of mice were 1?1 000 and 1?10 000-1?100 000, respectively. In addition to IgG,
      the serum IgA specific to VP6 could also be detected at a titer of 1?10-1?100.
      Secretory IgA(sIgA) was detected in both lung lavage fluid and intestinal
      homogenate when administered intranasally to BALB/c mice, whereas only found in
      intestinal homogenate in the oral group. The results indicated that the
      immunization efficacy of intranasal inoculation was superior to that of oral
      inoculation. CONCLUSIONS: The recombinant adenovirus vector expressing human
      rotavirus VP6 was successfully constructed, its ability to induce immune
      responses has laid a solid foundation for the development of rotavirus
      genetically engineering vaccine against rotavirus infection.

PMID- 12196820
TI  - [HIV-1 integrase enzyme linked immunosorbent assay and inhibitors].
AB  - BACKGROUND: To establish an ELISA method for detecting the activity of HIV-1
      integrase and screening of inhibitors. METHODS: HIV recombinant plasmid
      F185K/C280S IN1-288 was transformed into the E.coli strain BL21(DE3) integrase
      with a histag was induced by adding isopropyl-?-D?thiogalactopyranoside (IPTG)and
      purified by nickel affinity chromatography. The synthesized donor substrate
      oligonucleotide representing the HIV-1 U5LTR was immobilized onto covalink
      polystyrene microtiter plates, and a synthesized biotinlated 20 bp
      oligonucleotide was used as the target substrate. The products were detected and
      quantified using a colorimetic avidin?linked alkaline phosphatase reporter
      system,and identified by 32? autoradiography. Some natural products and
      chemically synthesized compounds were screened for HIV-1 integrase inhibitors.
      RESULTS: The purified integrase was identified by SDS?PAGE and showed integration
      activity by ELISA and?32P radioisotopic assay.?Coefficients of variation (CV)of
      ELISA in a lot and among the lots were 4.63% and 5.89% respectively, the mean of
      P/N was 2.836 0.161 under the optimal experimental condition. Some plant extracts
      were found as potent integrase inhibitors. The IC50s for CEH and CEHL were (20.41
      5.68)?g/ml and (7.56 1.86)?g/ml respectively. CONCLUSIONS: The authors have
      established a simple and rapid ELISA method with stable repeatability for
      detecting integrase activity, which can be used for screening and studying of
      specific inhibitors of HIV-1 integrase.

PMID- 12196821
TI  - [Modification of HPV type 16 E6 and E7 genes, and analysis of stability and
      immunogenicity of the modified proteins].
AB  - BACKGROUND: To select the mutants of HPV type 16 E6 and E7 genes suitable for
      construction of vaccine for treatment of cervical cancer. METHODS: E6 and E7
      genes were modified by site-directed mutagenesis. Several recombinant vaccina
      viruses were constructed by inserting the E6 or E7 mutants into the genome of
      vaccina virus Tiantan strain and employed to study their antigenicity. RESULTS:
      Western blot assay showed that the E6 ?mutant? with substitution of Gly for Leu
      at amino acid site 50 and E7 mutant with substitution of Gly for Cys-24 and Glu
      26 had no effect on their stability and antigenicity, but change of the Cys at
      position 91 of E7 dramatically reduced its stability and antigencity. Conclusion
      The results confirmed that the Zinc-finger structure at the E7 C-terminal? plays
      an important role in the integrity and stability of E7 protein.

PMID- 12196822
TI  - [Relationship between diversity of hepatitis C virus quasispecies and viremia,
      activity of liver disease and response to interferon therapy].
AB  - BACKGROUND: To determine the relationship between diversity of hepatitis C virus
      quasispecies and viremia, activity of liver disease and response to interferon
      therapy. METHODS: HCV quasispecies heterogeneity in 68 patients with chronic
      hepatitis C were detected by single stranded conformational polymorphism (SSCP)
      analysis of the HCV E2 hypervaribale region 1 (HVR1); of these, 48 were
      subsequently treated with interferon-alpha for 6 months. RESULTS: HVR1 was
      amplified in 61 patients. The average number of SSCP bands was 6.2+/-2.4.
      Quasispecies heterogeneity significantly correlated with serum HCV RNA levels
      (P<0.01), but not with serum ALT, AST levels and histological activity index
      (P>0.05). Of the patients who received interferon therapy, 43 were HVR1 positive.
      Patients who gained sustained response (n=11) had lower pre-treatement
      quasispecies heterogeneity (3.3+/-1.2) compared to those who had complete end-of
      treatment response (ETR) with relapse (6.3+/-2.2, n=12, P<0.5) or no response
      (8.0+/-3.3, n=20, P<0.01). At the end of treatment, HVR1 could still be detected
      in 16 patients. The number of quasispecies heterogeneity in these patients
      decreased to 3.4+/-1.2, which was significantly lower than that in the patients
      who didn't receive interferon therapy (6.8+/-2.5, P<0.01). Of these 16 patients,
      10 had change in quasispecies patterns. CONCLUSIONS: Increased quasispecies
      heterogeneity can cause high HCV viremia, but it is not related to severity of
      liver disease. Quasispecies heterogeneity is another marker to predict the
      response to interferon-alpha in patients with chronic hepatitis C.

PMID- 12196823
TI  - [Mutation of LoopAB in HuIFN 1c/86D and enhancement of antiviral activity].
AB  - BACKGROUND: Based on the earlier mapping of the epitope recognized by
      neutralizing antibody, the authors directly replaced binding domain of IFN in AB
      loop for enhancement of biological activity. METHODS: Two unique restriction
      sites (EcoR? and BsE?) were created into region flanking LoopAB. Casette
      mutagesis, restriction enzyme digestion, DNA sequencing, antiviral activity assay
      and antiproliferative activity assay have been used in the project. RESULTS: The
      mutated residues M31?D,D32?P of LoopAB in parent IFN were produced. The
      recombinant phagemid pCANTAB5E/3132IFN 1c/86D and expression plasmid PBV322
      132IFN 1c/86D were constructed respectively by replacing the corresponding LoopAB
      with DNA fragment mutated in the residues M31?D,D32?P, which have been confirmed.
      The recombinant protein has been expressed in E.coli JM103. The crude 3132IFN
      1c/86D has been assayed on human WISH cells challenged with VSV and on HeLa cells
      by colorimetric MTT. 3132IFN 1c/86D showed 8-old antiviral activity compared to
      that of parent IFN 1c/86D, while IFN?induced growth inhibition of both types had
      no difference. CONCLUSIONS: The authors concluded that a mutant IFN with enhanced
      antiviral activity can be obtained via a targeted replacement of receptor binding
      domain in AB-loop.

PMID- 12196824
TI  - [Expression of IL-6 in recombinant non-replicating vaccinia virus and studying
      its effects on immunogenicity].
AB  - BACKGROUND: To investigate expression of IL-6 in non?replicating vaccinia virus
      and its immune effects on recombinant virus. METHODS: The recombinant non
      replicating vaccinia virus RVJ123 delta CK11 beta 75IL6 was constructed with
      non?replicating vaccinia virus vector pNEOCK11beta75IL6 and replicating vaccinia
      virus RVJ123. In animal model, immunization with the recombinant virus was
      carried out and its immune response was studied. RESULTS: The recombinant virus
      could express IL-nd HBsAg simultaneously. Southern blot analysis demonstrated
      that the genes between vaccinia virus Hind? C and K fragments were deleted and IL
      6 gene was integrated stably. Given intranasal inocula of the virus to immunize
      BALB/c mouse and New Zealand Rabbit, the elevated anti-HBsAg IgA and IgG antibody
      secreting cells in mouse lung lymphoid to vectors expressing IL-6 was at about
      two?fold higher level than those elicited by control virus at day 14 after
      immunization. Authors also could detect elevated anti-HBsAg IgA and IgG antibody
      conversion in mouse serum and lung fluid, rabbits serum, lung fluid, saliva,
      vagina and nasal washing samples. CONCLUSIONS: IL-6 expressed by non-replicating
      recombinant vaccinia virus could enhance the induced?immune effects, it could
      serve as the effective adjuvant for recombinant vector vaccine.

PMID- 12196825
TI  - [Characterization of genome of A/Guangzhou/333/99(H9N2) virus].
AB  - BACKGROUND: To understand the characterization of genome of a strain of avian
      influenza A H9N2 virus repeatedly isolated from a child with influenza illness.
      Thereafter to reveal the origin of this H9N2 virus. METHODS: Viruses were passed
      in embryonated hen eggs and virion RNA was extracted from allantoic fluid and
      reverse transcribed to synthesize cDNA. cDNA was amplified by PCR and the PCR
      product was purified with a purification kit. Afterwards RNA sequence analysis
      was performed by dideoxynucleotide chain termination and a cloning method.
      Finally, phylogenetic analysis of the sequencing data was performed with MegAlign
      (Version 1.03) and Editseg (Version 3.69) softwares. RESULTS: Genome of
      A/Guangzhou/333/99 (H9N2) virus was closely related to avian influenza A H9N2
      virus, but obvious difference from that of A/Duck/Hong Kong/Y439/97(H9N2) virus,
      as well as its genome did not include any RNA segment derived from human
      influenza A virus. However, the genes encoding the HA,NA,NP and NS proteins of
      A/Guangzhou/333/99 virus were derived from those of G9 lineage virus, the rest
      genes encoding the M and three polymerase (PB2,PB1 and PA) proteins were derived
      from G1 lineage strain. CONCLUSIONS: A/Guangzhou/333/99 virus was a reassortant
      derived from reassortment betweenG9 and G1 lineages of avian influenzaA(H9N2)
      viruses. Therefore, the most possibility is that it is derived from avian
      influenza A virus directly. The results do not only demonstrate that avian
      influenza A (H9N2) virus could infect men, but also firstly prove that the
      genetic reassortment could be occurred between different genetic lineages of
      avian influenza A (H9N2) viruses in the nature.

PMID- 12196826
TI  - [Long-term efficacy and persistence of Chinese infants after receiving only
      active plasma-derived hepatitis B vaccine].
AB  - BACKGROUND: To determine the long-term efficacy and persistence of Chinese
      infants after receiving only active plasma-derived hepatitis B vaccine, and to
      evaluate if providing booster vaccination after basic hepatitis B immunization is
      necessary. METHODS: Infants who were born in 1986-1988 in four demonstrative
      hepatitis B immunization trial areas of Hunan, Guangxi, Hebei and Shanghai after
      receiving only active plasma-derived hepatitis B vaccination, had been randomly
      followed up for 15 years. HBsAg,anti-HBs and anti-HBc in 21 680 person-times were
      tested using commercial SPRIA kits. RESULTS: Prevalence of HBV carriers was less
      than 1.66% among all children vaccinated with only active plasma-derived
      hepatitis B vaccine in 4 clinical trial areas. Prevalence of HBsAg did not
      increase with years after vaccination,90%(95% Cl:83.1%-97.2%) effectiveness of
      hepatitis B vaccine persisted for 15 years in preventing chronic HBV infection.
      Carriage, HBV infection and efficacy were not different among all age groups
      (P>0.05). Seroprotection rate (anti-HBs?10 mIU/ml) and quantity of anti-HBs were
      significantly decreased with years after vaccination. Seroprotection rates of
      anti-HBs were 40%-50% and 30%-42% during the 9th-10th year and the 13th-14th ear
      of vaccination, respectively. Titer of anti-HBs declined?by 90% after 14 years.
      CONCLUSIONS: These results showed that long-term efficacy of only active plasma
      derived hepatitis B vaccination, which was not affected by decline in
      seroprotection rate and titer of anti-HBs. For children and adults whose immune
      status is normal, booster doses of vaccine are not recommended.

PMID- 12196827
TI  - [Expression and antigenicity analysis of hepatitis G virus NS5 gene].
AB  - BACKGROUND: To determine the antigenicity of HGV NS5 recombinant proteins
      expressed in E.coli. METHODS: HGV NS5a,NS5b and core/NS5b fusion genes were
      cloned into pThioC vector. Three expression plasmids were transformed into
      JM109(DE3) competent cells then expressed with induction by IPTG. Western blot
      and ELISA were used to determine the antigenicity after the three recombinant
      proteins were purified. RESULTS: After identification by restriction enzyme and
      sequencing, it was confirmed that the expressed was target proteins espected.
      Purified expression proteins were found strongly immunoreactive among anti HGV
      positive sera by Western blot and ELISA. Compared with mixed recombinant antigen
      (including core, NS5a synthetic peptide and NS3 recombinant proteins), in the 22
      positive sera detected with mixed antigen, 68%(15/22), 90%(20/22) and 73%(16/22)
      were positive by P5a,P5b and Pc?5b antigens; In the 70 negative samples with
      mixed antigen, 7%(5/70), 1%(1/70) and 6%(4/70) were positive by P5a, P5b and
      Pc?5b antigens. The positive alone was found among RTPCR positive specimen using
      these recombinant antigens. CONCLUSIONS: NS5 gene expressed in E.coli?which
      couldn't be covered with other regions of antigens was one of the essential
      epitopes to HGV immunologic diagnosis.

PMID- 12196828
TI  - [Transcriptional activation function of hepatitis B virus Pre S1 protein in
      yeast].
AB  - BACKGROUND: To explore the feasibility of cloning of the hepatocyte receptor
      interacting with the Pre S1 protein of HBV by two hybrid system. METHODS: Yeast
      expression plasmids encoding fusion proteins of full length or portions of Pre S1
      of HBV and DNA binding domain of yeast protein GAL4 were constructed and used to
      transform yeast reporter strain SFY526. Reporter gene product ?galactosidase
      activity was assayed as a measure of transcription activation in yeast. Mammalian
      expression plasmid encoding fusion proteins of full length Pre S1 and DNA binding
      domain of GAL4 was constructed and used to cotransfect hepatoma cell line Huh?7
      together with CAT reporter plasmid. Cell extracts were assayed for CAT activity
      by thin?layer chromatography. RESULTS: The fusion proteins of full length Pre S1
      protein and GAL4 DNA binding domain present transcriptional activation function
      in yeast. The transcription activating sequence is localized to the 21 to 47
      amino acids of Pre S1 protein Fusion proteins of full length Pre S 1 and GAL 4
      DNA binding domain do not show transcriptional activation function in mammalian
      cells. CONCLUSION: The transcriptional activating sequence of HBVPre S1 protein
      in yeast overlaps the hepatocyte receptor binding site. The transcriptional
      activation function of HBV Pre S1 protein in yeast may prevent researchers?from
      using yeast two hybrid system to clone HBV receptor interacting with Pre S1
      protein. However, the Pre S1 protein does not show transcriptional activation
      function in mammalian cells. Mammalian two?hybrid system may be a practical
      method to clone the HBV hepatocyte receptor interacting with Pre S1 protein.

PMID- 12196829
TI  - [Treatment of severe viral hepatitis with artificial liver support system].
AB  - BACKGROUND: To investigate the method and therapeutic efficacy of artificial
      liver support system (ALSS) in treatment of severe viral hepatitis. METHODS: A
      total of 83 patients including 66 with severe viral hepatitis were treated with
      ALSS using Baxter-550 artificial kidney and Biologic-DT system. RESULTS: The
      levels of mean bilirubin, ALT, AST, BUN, Cr and endotoxin was significantly
      decreased after the treatment. Of the 66 patients?with severe viral hepatitis,
      31(47.0%) had improvement in symptoms and 35 (53.0%) died or left hospital. In
      the control group,50(27.6%) out of the 181 had improvement in symptoms and
      131(72.4%) died or left hospital. CONCLUSIONS: ALSS could exert certain
      therapeutic effects on severe viral hepatitis.

PMID- 12196830
TI  - [Detection of the HBV DNA with Sybr green 1 realtime polymerase chain reaction].
AB  - BACKGROUND: To search a novel sensitive, specific and lower cost method
      applicable for quantitative analysis of the hepatitis B virus DNA extensively.
      METHODS: Quantitative analysis of the DNA from 100 sera by real-time PCR with
      Sybr green 1. The results of Sybr's assay were compared with the results obtained
      with Taqman's fluorescent quantitative assay. RESULTS: Taqman real-time PCR could
      help evaluate the level of virus reliably. The results of Sybr's assay were in
      agreement with the Taqman's assay, but detection rate was lower. CONCLUSIONS:
      Sybr green 1 real-time PCR appeared to be convenient and cheap, but detection
      rate was lower.

PMID- 12196831
TI  - [Construction and expression of recombinant retrovirus vector carrying HBV
      vector].
AB  - BACKGROUND: To explore the possibility of using retrovirus vector to carry HBV
      vector, and to prove that replication defective HBV could be normally packaged.
      METHODS: Two kinds of full length of mutant HBV gene, which express dominant
      negative mutants, were inserted into retrovirus vector. After recombinant
      retroviruses were harvested, they were used to infect Hep G2 and 2.2.15 cell
      line. Then the expression of HBV core antigen in the Hep G2 cell was examined by
      immune fluorescence, and the existence of recombinant HB virion in the culture
      medium was examined by PCR. RESULTS: High titer of recombinant retroviruses were
      obtained in the culture medium of transfected PA317 cell line. Core antigen was
      detectable in the recombinant retrovirus infected Hep G2 cell. Recombinant HB
      virion was detectable in the culture medium of recombinant retrovirus infected
      2.2.15 cell. CONCLUSIONS: The results suggested that recombinant retrovirus could
      carry HBV vector and express HBV products. When structural protein is offered by
      wt-HBV, the recombinant retrovirus may function as HBV vector, therefore it could
      be used in anti?HBV gene therapy.

PMID- 12196832
TI  - [Influence of labeled primer and labeled dUTP assays on the signal intensity of
      the chip for the detection of HBV gene polymorphism].
AB  - BACKGROUND: To evaluate the influence of assays with primer labeled with
      fluorochrome (Cy5) and dUTP labeled with Cy5 on the signal intensity of the chip
      for detection of hepatitis B virus (HBV) gene polymorphism. METHODS: The P-region
      and pre-C/C-region of HBV gene were amplified by polymerase chain reaction (PCR)
      with Cy5 labeled primer or Cy5 labeled dUTP. The amplicons of the two assays were
      hybridized with chips, scanned and analyzed by computer software for the
      detection of HBV gene polymorphism. RESULTS: The signal intensity of assay with
      Cy5 labeled dUTP was slightly higher than that of assay with Cy5 labeled primer,
      but non?specific signal intensity of the assay with Cy5 labeled dUTP was higher.
      The result of 42 samples showed that there was no significant difference between
      the two assays, and that both had a good repeatability and CV value (15%-20%).
      CONCLUSIONS: The assay with Cy5 labeled primer may replace the assay with Cy5
      labeled dUTP as a routine method to detect HBV gene polymorphism, and it is
      simpler and cheaper.

PMID- 12196834
TI  - [Functional effects of dendritic cells transfected with Epstein-Barr virus latent
      membrane protein 2A recombinant adenovirus].
AB  - BACKGROUND: To study the effects of dendritic cells (DC) transfected with
      recombinant adenovirus encoding Epstein-Barr virus(EBV)latent membrane protein
      2A(LMP2A)gene, and to provide evidence for further investigation on the
      therapeutic vaccine against EBV-associated malignancies. METHODS: DCs were
      transfected with EBV-LMP2A recombinant adenovirus (Ad5-LMP2A), which was
      generated by homologous recombination. The expression of LMP2A protein on mature
      DC transfected with Ad5-LMP2A at different multiplicity of infection(MOI)was
      analyzed by fluorescence activated cell sorting(FACS), and the dead cells were
      counted by trypan blue staining. The alteration of surface markers on mature DC
      including CD1a, CD83, CD40, CD80, HLA?DR was detected by means of FACS before and
      after transfection. Meanwhile, the functions including stimulating allogenetic T
      cells reaction and expressing IL12 P40 mRNA on transfected DC were measured by
      methods of 3H-thymidine uptake and fluorescent semi?quantitative polymerase chain
      reaction (PCR), respectively. RESULTS: About 80% mature DC expressed LMP2A
      protein and >92% cells were viable after transfection at the MOI of 200 No.
      significant changes in the surface markers and the cytomorphology of mature DCs
      were detected during the transfection. Transfected DC still have strong potential
      to stimulate the proliferation of allogenetic T cells and to express IL-12 P40
      mRNA. CONCLUSION: EBV-LMP2A gene,which was carried by adenovirus vectors, could
      be transferred into DC with high efficiency. The function of mature DC was not
      affected significantly by the transfection of Ad5-LMP2A.

PMID- 12196833
TI  - [Cloning and expression of simplex herpes virus ? US4 fragment].
AB  - BACKGROUND: To get early laboratory study of type specific antigenicity of herpes
      simplex virus II. METHODS: PCR and prokaryotic expression technique. RESULTS:
      Herpes simplex virus II type specific gene fragment was expressed in E.coli and
      the products can be used as specific antigen for the detection of anti?HSV in the
      recovery sera. CONCLUSIONS: Cloning and express of HSVII type specific antigen
      found the basis for developing specific diagnosis methods and vaccine of HSV.

PMID- 12196835
TI  - [Cloning and expression of HSV-I, II type-common antigen gD in Escherichia coli].
AB  - BACKGROUND: To clone the type common antigen gD of human herpes simplex virus I,
      II (HSV-I, II), the authors constructed recombinant expression vector Pmal-c2/gD
      and induced to express the fusion protein MBP-gD. METHODS: The authors extracted
      HSV DNA,amplified gD gene by PCR assay and directly cloned it into prokaryotic
      expression vector pMAL-c2, then transformed it into E.coli DH5alpha. After proved
      to be correct by PCR, double enzyme digestion and sequencing, the fusion protein
      is induced to express by IPTG and detected by both Western blot and ELISA.
      RESULTS: The constructed expression vector pMAL-c2/gD can be expressed with high
      efficiency. The product expressed was about 35.5% of the total bacterium proteins
      by SDS?PAGE analysis and was found nearly 39% as soluble protein,61% as inclusion
      in cytoplasm. CONCLUSIONS: The authors constructed recombinant expression vector
      pMAL-c2/gD, the Western blotting result showed that the recombinant protein could
      be identified with gD specific monoclonal antibody DL6. Therefore the protein was
      of natural antigenic structure of gD.

PMID- 12196836
TI  - [The relationship of cervical cancer with pathogen infectious, cytokine and Se].
AB  - BACKGROUND: To identify the relationship of cervical cancer with pathogen
      infectious, cytokine and Se. METHODS: On the one hand regarded tissues of the
      carcinoma of the uterine cervix with 195 cases as the experimental group and
      ordinary cervical tissues with 75 cases as the control group. Polymerase chain
      reaction (PCR) to detect them. On the other hand applied ELISA to detect cytokine
      IL-2R, TNF and fluorescent luminosity technique to detect element Se in the
      serums. RESULTS: In the experimental group those infected pathogen were 166 cases
      (85.1%), In all of pathogen HPV 16,18,35 type were 60 cases (30.8%), HSV 2 were
      60 cases (30.8%), While those ordinary tissues infected pathogen were 15 cases
      (20 0%),in the contrast group. HPV 16,18,35 type and HSV 2 mere 4.0% and 6.7%
      respectively,(P<0.001). In the serums of effective 62 experimental objects IL-2R
      (x=356.44 U/ml) and TNF (x=373.48 pg/ml) were much high than them in the serums
      of effective 36 contrast objects (P<0.001). But Se (x=0.058 mg/ml) was lower than
      it in the serums of contrast objects (P<0.05). CONCLUSIONS: The occurrence of
      carcinoma of the uterine cervix is closely connected with infection of HPV
      16,18,35 and HSV2, high level of cellular factors IL-2R, TNF and low level of
      element Se.

PMID- 12196837
TI  - [Expression, purification and diagnostic application of EBV TK kinase].
AB  - BACKGROUND: To find a rapid and sensitive method for early diagnosis of
      nasopharyngeal carcinoma by using EBV TK kinase. METHODS: Prokaryotic expression
      plasmid pRSETTK was constructed. EBV TK kinase was highly expressed in E.coil
      BL21 (DE3). The authors identified specificity of TK kinase by Western blot, then
      used purified TK kinase in ELISA to detect the IgG antibody in the serum of NPC
      patients. RESULTS: Specific IgG antibody against TK kinase was found in the serum
      of NPC patients. The specificity and sensitivity of TK kinase were both 100% in
      Western blot and were 98.0% and 93.4% respectively in ELISA. CONCLUSIONS: The EBV
      TK kinase showed high specificity and sensitivity in ELISA, therefore it can be
      used for early diagnosis of NPC

PMID- 12196838
TI  - [Detection of human cytomegalovirus infection by FQ-PCR technique and its
      application in the diagnosis and treatment of HCMV infected children].
AB  - BACKGROUND: To detect quantitatively HCMV DNA in peripheral blood leukocytes to
      monitor the status of HCMV infection, evaluate the effectiveness of antiviral
      treatment with ganciclovir (GCV) combined with intravenous immunoglobulin (IVIG)
      and find out the relationship among the HCMV DNA levels, the state of infection
      and the clinical outcome.The long-term goal of the study was to establish a
      molecular diagnostic standard for HCMV infection in children. METHODS: 45 cases
      of suspected HCMV-infected children were examined by PCR, ELISA and fluorescent
      quantitative (FQ)-PCR, respectively. Twenty five HCMV hepatitis cases of the 45
      were randomly assigned to a treated group or a control group. Both groups were
      treated with prednisone, glucurone, Luminal and Xiaoyanlidanpian. But the treated
      group was given with GCV+IVIG in addition. Each infant of the two groups was
      checked with FQ-PCR at the five time points. RESULTS: The positive rates of PCR,
      ELISA and FQ-PCR were 60.00%, 33.33% and 66.67%,their sensitivities were 84.38%,
      46.88% and 93.75%, respectively. There was no significant difference in viral DNA
      copy numbers between the two groups before being treated (P>0.05), but there was
      significant difference between HCMV hepatitis and normal infants (P<0.001).
      Although viral load of both groups decreased in both groups, the viral load of
      the treated group decreased more significantly. The level of HCMV DNA fell to 103
      copies/ml at second time point while that of the control group fell to the same
      level after third time point. The differences between the two groups at each time
      point were statistically significant (P<0.001). The results of 135 person times
      testing indicated that 103 copies/ml of FQ-PCR can be taken as a critical value
      for prediction of active HCMV infection. CONCLUSIONS: FQ-PCR may be one of the
      effective methods for diagnosis of HCMV disease; it can offer a key index in the
      diagnosis of HCMV active infection; dynamic detection of HCMV viral load can play
      a role not only in monitoring antiviral therapy, but also in evaluating the
      development and prognosis of HCMV disease.

PMID- 12196839
TI  - Smoking cessation in pregnancy: are we doing enough?

PMID- 12196840
TI  - Effects of cancer treatment on reproduction and fertility.
AB  - OBJECTIVE: (1) To review the effects of cancer treatment on reproduction and
      fertility in both women and men and (2) to review current and new techniques that
      could be used to preserve fertility and hormone production in women who have
      undergone cancer treatment. DATA SOURCES: Entries to MEDLINE and CANCERLIT
      through to October 2001 were searched for evidence relevant to this article.
      METHODS OF STUDY SELECTION: This document is primarily based on large
      retrospective cohort series and case reports, as no randomized trials were
      available. TABULATION, INTEGRATION, AND RESULTS: The first part of this review
      article focuses on the effects of radiation and chemotherapy on reproductive
      function and innovative medical and surgical techniques employed to minimize
      these effects. The second part of this article describes conservative methods of
      managing cervical, endometrial, and ovarian cancer for women who wish to preserve
      their fertility. CONCLUSIONS: Over the last decade, there has been a trend toward
      trying to preserve reproductive function in young patients with malignancy.
      Information acquired over the last century on the reproductive effects of
      radiation and chemo-therapy has enabled us to tailor our treatment of various
      malignancies affecting young patients. As we learn more about the biology and
      clinical behaviour of gynaecologic malignancies, we are able to modify surgical
      management to preserve fertility in select cases. All of these trends are in
      keeping with our goal to optimize quality of life in cancer care without
      compromising safety or survival.

PMID- 12196841
TI  - The role of serum uric acid as a prognostic indicator of the severity of maternal
      and fetal complications in hypertensive pregnancies.
AB  - OBJECTIVE: To examine whether an elevated serum uric acid level in hypertensive
      pregnant women is a useful prognostic indicator of severe hypertension;
      hemolysis, elevated liver enzymes, low platelets (HELLP) syndrome; and small for
      gestational age (SGA) infants. METHODS: A total of 459 women newly diagnosed with
      hypertension in pregnancy were categorized into "gestational hypertension" and
      "hypertension with proteinuria (preeclampsia)" groups. Their serum uric acid
      levels were correlated with the development of HELLP syndrome, severity of
      hypertension, and incidence of SGA newborns (< 10th percentile birth weight).
      HELLP syndrome was divided into 3 classes depending on the severity of the
      thrombocytopenia. Prior to this study, serum uric acid levels had been measured
      in a group of normotensive women. Mean and standard deviation of serum uric acid
      levels for each group were compared using analysis of variance and student t
      tests, where necessary. RESULTS: Significant elevation in serum uric acid levels
      over normotensive pregnant women (285 +/- 72 micromol/L) was observed in both the
      gestational hypertensive group (341 +/- 83 micromol/L) and the preeclamptic group
      (384 +/- 93 micromol/L) of women (p < 0.001 and p < 0.05 respectively). Serum
      uric acid levels were also significantly elevated (p < 0.001) in women with
      gestational hypertension with HELLP syndrome (382 +/- 78 micromol/L) compared to
      those without HELLP syndrome (330 +/- 80 micromol/L). Preeclamptic women with
      HELLP syndrome (412 +/- 99 micromol/L) also demonstrated elevated uric acid
      levels (p < 0.05) over those without HELLP syndrome (374 +/- 87 micromol/L).
      However, the level of uric acid did not predict the severity of HELLP syndrome.
      The presence of SGA infants in the gestational hypertensive group was not
      associated with increased uric acid levels. CONCLUSION: Uric acid levels,
      although significantly elevated in women with gestational hypertension and
      preeclampsia as compared to normotensive pregnant women, are not good prognostic
      indicators of the severity of the maternal or fetal complications.

PMID- 12196842
TI  - Influence of aboriginal and socioeconomic status on birth outcome and maternal
      morbidity.
AB  - OBJECTIVE: To assess the association of Aboriginal and socioeconomic status with
      birth outcome and maternal morbidity in Alberta. METHODS: A retrospective cohort
      study using Alberta health service and vital statistics data from 1997 to 2000.
      Aboriginal women registered with the Department of Indian and Northern
      Development (DIAND) were linked to a personal health number. Low socioeconomic
      status was defined as either receiving subsidization for the Alberta Health Care
      Insurance premium or receiving welfare. RESULTS: Women registered with DIAND and
      women receiving subsidy or welfare were younger, more often unmarried, smoked
      more, consumed more alcohol, and abused more illicit drugs than other women in
      Alberta during the time period studied. Fewer women registered with DIAND and
      women receiving subsidy or welfare had physician prenatal visits, attended
      prenatal classes, had forceps or vacuum deliveries, and more of these women
      frequently had gestation ages less than 37 weeks. Women registered with DIAND had
      more deliveries in smaller, non-metropolitan facilities; and more of these women
      delivered outside their region of residence; more had longer lengths of hospital
      stay; more mothers and neonates were re-admitted to hospital within 28 days of
      discharge after delivery; fewer delivered small for gestational age neonates;
      fewer delivered neonates with birth weight less than 2500 g, but more delivered
      neonates with birth weight greater than 4000 g. There were fewer Caesarean
      sections in women registered with DIAND (OR = 0.84, 95% CI 0.76-0.93) and in
      women receiving subsidy or welfare (OR = 0.88, 95% CI 0.82-0.93). CONCLUSION:
      Women receiving subsidy or welfare and women registered with DIAND had many
      demographic similarities and generally had worse maternal and neonatal outcomes
      than other women in Alberta. Medical system interaction may be different for
      these two groups of women than it is for other women in Alberta.

PMID- 12196843
TI  - History of the Atlantic Society of Obstetricians and Gynaecologists.
AB  - The origins and development of the Atlantic Society of Obstetricians and
      Gynaecologists from 1961-2001 is outlined.

PMID- 12196844
TI  - Cystic fibrosis carrier testing in pregnancy in Canada.
AB  - OBJECTIVE: To assess the role of cystic fibrosis (CF) testing within the Canadian
      health care environment. METHODS: The Genetics and Maternal Fetal Medicine
      Committees of the Society of Obstetricians and Gynaecologists of Canada (SOGC)
      reviewed Preconception and Prenatal Carrier Screening for Cystic Fibrosis
      Clinical and Laboratory Guidelines produced by the American College of
      Obstetricians and Gynecologists (ACOG) and the American College of Medical
      Genetics (ACMG) and other educational material from ACOG and ACMG. RESULTS:
      Background information related to cystic fibrosis, genetic mutation analysis, and
      one large clinical cystic fibrosis screening trial are reviewed. EVIDENCE: The
      quality of evidence reported in this document has been described using the
      Evaluation of Evidence criteria outlined in the report of the Canadian Task Force
      on the Periodic Health Exam. RECOMMENDATIONS: 1. CF testing in pregnancy is
      indicated for individuals who may be at increased risk for CF due to
      considerations of family history or clinical manifestations. (II-2A). 2. Before
      CF screening could be undertaken, each province/territory would have to review
      the ethnic diversity of its reproductive population to ensure that CF screening
      would be appropriate. (III-C). 3. Screening of all women during pregnancy for CF
      carrier status cannot be recommended at this time. (III-C).

PMID- 12196845
TI  - SOGC president's inaugural address.

PMID- 12196846
TI  - Referral patterns for gynaecologic cancers and precancerous conditions.
AB  - OBJECTIVES: (1) To determine a gynaecologist's preference for delivering primary
      surgical care to women with gynaecologic cancer or precancerous conditions; (2)
      to determine referral patterns for gynaecologic cancers and precancerous
      conditions; (3) to outline barriers to the current gynaecologic oncology service
      provision in Ontario; (4) to understand, from a gynaecologist's perspective, the
      acceptable waiting times from referral to subspecialty consultation; and (5) to
      determine a gynaecologist's interest in following patients after more specialized
      management for gynaecologic cancer. METHODS: The survey instrument was designed
      and pretested. The survey was mailed to 541 gynaecologists in Ontario. RESULTS:
      The response rate was 49.4%. Of the gynaecologists who responded, 75.3% trained
      in Ontario; 57.3% had community-based practices; and 55% indicated they
      surgically treated women with invasive cancers. The invasive cases treated most
      commonly were endometrial cancer (96.4%), followed by ovarian cancer (86.1%).
      Ninety-one percent of gynaecologists referred their patients to the closest
      cancer centre with a gynaecologic oncologist on staff. Seventy-five percent of
      gynaecologists were interested in delivering follow-up care for women who had
      treatment for cancer, provided that follow-up guidelines were made available.
      CONCLUSION: Gynaecologists were interested in providing follow-up care to women
      who received cancer care by subspecialists. Gynaecologists requested continuing
      education on gynaecologic cancers and guidelines for follow-up care. Issues
      surrounding the process of referral and communication with gynaecologists were
      seen as areas for improvement. The results of this survey will be pivotal in
      setting goals for a provincial gynaecologic oncology program.

PMID- 12196847
TI  - Oral contraceptives as anti-androgenic treatment of acne.
AB  - Although acne is seldom associated with high serum levels of androgens, it has
      been shown that female acne patients have definite increases in ovarian and
      adrenal androgen levels when compared to appropriate controls. As shown in
      several pilot and in multiple open and comparative studies, oral contraceptives
      (OCs) are effective in causing a significant regression of mild to moderate acne.
      These results have been confirmed by multicentre randomized trials where low-dose
      OCs did not cause side effects different from those of the placebo-controlled
      group. The beneficial effect of OCs is related to a decrease in ovarian and
      adrenal androgen precursors; to an increase in sex hormone-binding globulin
      (SHBG), which limits free testosterone; and to a decrease in 3a-androstenediol
      glucuronide conjugate, the catabolite of dihydrotestosterone (DHT) formed in
      peripheral tissues. The estrogen-progestin combination containing cyproterone
      acetate (CPA) is particularly effective in treating acne, since this progestin
      also has a direct peripheral anti-androgenic action in blocking the androgen
      receptor. Only two open studies and one randomized study on small numbers of
      patients have reported some efficacy of spironolactone used alone or in
      combination with an OC in the treatment of acne. The new non-steroidal anti
      androgens flutamide and finasteride are being evaluated for the treatment of
      hirsutism. Oral antibiotics are prescribed to patients with inflammatory lesions,
      where they are effective in decreasing the activity of microbes, the activity of
      microbial enzymes, and leukocyte chemotaxis. Concomitant intake of an OC and an
      antibiotic usually prescribed for acne does not impair the contraceptive efficacy
      of the OC. A second effective contraceptive method should be used whenever there
      would be decreased absorption or efficacy of the OC (digestive problems,
      breakthrough bleeding), lack of compliance and use of a type or dose of
      antibiotic different from that usually prescribed for acne.Overall, the various
      approaches for the treatment of acne depend on the needs of the patient and on
      the therapeutic objectives. Low-dose OCs are effective in improving acne and have
      side effects similar to placebo. They can be used alone or in combination with
      other anti-acne agents. The physician prescribing an OC as an anti-androgen
      intervention should take into account the multiple factors involved in acne and
      be familiar with current non-hormonal agents for treating mild to moderate acne.
      Individuals presenting with moderate to severe acne, or not responding to an
      estrogen-progestin combination, should be referred to a dermatologist.

PMID- 12196848
TI  - Use of low molecular weight heparin in acute venous thromboembolic events in
      pregnancy.
AB  - OBJECTIVE: To compare the maternal and neonatal outcomes arising from the use of
      low molecular weight heparin (LMWH) or unfractionated heparin (UFH) in the
      treatment of acute venous thromboembolism (VTE) in pregnancy. STUDY DESIGN: A
      retrospective review of the charts of all women treated for acute VTE in
      pregnancy at the Ottawa Hospital from January 1990 to December 1999. RESULTS:
      Twenty-three cases were identified, of which 11 were treated with LMWH and 12
      with UFH. Maternal and fetal outcomes were similar between the two groups.
      Hospital length of stay was shorter in the LMWH group. There was no difference in
      delivery management between the two groups. There was minor bleeding in 2 women
      in the UFH group and none in the LMWH group. There was one recurrent VTE during
      treatment in each of the groups. CONCLUSION: There is no difference in
      complication rate between LMWH and UFH in the treatment of acute VTE in
      pregnancy.

PMID- 12196849
TI  - What women want: don't call us clients,and we prefer female doctors.
AB  - OBJECTIVE: To determine the descriptive word for women that women attending
      obstetrical and gynaecological clinics deemed most suitable and whether the women
      preferred to be cared for by male or female practitioners. METHODS: A
      questionnaire administered to 200 women attending specialty antenatal and general
      gynaecology clinics. RESULTS: Those attending the antenatal clinic chose as
      follows: "patient" (63.5%), "mother" (18%), "pregnant woman" (13.5%), "woman"
      (3%), and "client" (2%). Physician preference was: female (52.5%), male (1.5%),
      and either (46%). In the gynaecology clinic the choice was "patient" (68.5%);
      "woman" (24%); "client," "consumer," or "customer" (7.5%). Physician preference
      was: female (54.5%), male (2%), and either (43.4%). CONCLUSION: The descriptive
      word "patient" was the first choice of women attending antenatal and gynaecology
      clinics. The commercial words "client," "consumer," and "customer" were the least
      favoured. Given a choice, more than half of the women preferred to see a female
      physician, and preferred to be described as patients.

PMID- 12196850
TI  - Fertility following laparoscopic removal of rudimentary horn with an ectopic
      pregnancy.
AB  - BACKGROUND: Rudimentary horn pregnancies are rare. Although there have been
      previous reports of laparoscopic management, reports of successful pregnancies
      following previous excision of rudimentary horn were not found. Laparotomy
      remains the more common approach. CASE PRESENTATION: We report the story of a
      woman found to have a rudimentary horn pregnancy who chose to be managed
      laparoscopically, and subsequently became pregnant and delivered a viable term
      infant 15 months following laparoscopic surgery. DISCUSSION: The laparoscopic
      approach proffers decreased hospital stay, operating time, and potential for
      adhesions and is thus an important option for treatment of rudimentary horn
      pregnancies.

PMID- 12196851
TI  - Hormone replacement therapy and cardiovascular disease.

PMID- 12196852
TI  - Providing opinion for medico-legal cases.
AB  - This Committee Opinion outlines the guiding principles and a format for the
      physician who is requested to provide a peer opinion for a medico-legal case. The
      format allows for completeness, uniformity, and consistency in the preparation of
      expert opinions given in medico-legal cases. This Committee Opinion outlines the
      different elements that should enable lawyers and the courts to assess the weight
      of the opinion, its factual basis, and the reasons for opinions expressed.

PMID- 12196854
TI  - Bone densitometry: applications and limitations.
AB  - Osteoporosis is clinically diagnosed in its advanced stages, usually following a
      fracture. Accurate, precise, and noninvasive skeletal assessment is now possible
      for early detection of osteoporosis at a preclinical stage. Currently, the gold
      standard in bone mass measurement and fracture prediction is dual energy X-ray
      absorptiometry (DEXA) of the hip and spine. Exponential increases in fracture
      risk have been observed with small decreases in bone mineral density. Bone
      mineral density (BMD) should be considered in conjunction with independent
      clinical risk factors for fracture, including: low body weight, history of
      postmenopausal fracture, family history of fracture, and poor neuromuscular
      function. The World Health Organization (WHO) diagnostic criteria for
      osteoporosis and osteopenia are appropriate for postmenopausal Caucasian women
      and are applicable to DEXA assessments at the hip, spine, or forearm. This review
      explores the relationship between BMD and fracture risk, the principles of bone
      densitometry interpretation, and the applications as well as the limitations of
      DEXA technology, and presents cases illustrating common errors seen in the
      interpretation of DEXA studies.

PMID- 12196855
TI  - The impact of parity on the incidence of HELLP syndrome and small for gestational
      age infants in hypertensive pregnant women.
AB  - OBJECTIVES: To determine whether maternal and fetal complications such as HELLP
      (hemolysis, elevated liver enzymes, low platelets) syndrome and the incidence of
      small for gestational age infants in women with preeclampsia and gestational
      hypertension differ with both gravidity and parity. STUDY DESIGN: The charts of
      441 hypertensive women, 182 with preeclampsia and 259 with gestational
      hypertension, presenting for delivery at B.C. Women's Hospital were
      retrospectively reviewed. Multiple clinical parameters, including gestational age
      at presentation, the incidence of small for gestational age (SGA) infants, HELLP
      syndrome, and the severity of pre-eclampsia, were compared among three groups of
      women: (A) primigravid primiparous, (B) multigravid primiparous, and (C)
      multiparous. Mean values between the groups were compared using analysis of
      variance with pair-wise comparison using the Tukey test. RESULTS: The incidence
      of HELLP syndrome among the women with preeclampsia was similar in groups A and B
      (35% and 50%, respectively), but significantly lower (p < 0.012) in group C
      (19%). The incidence of small for gestational age infants among the women with
      preeclampsia was similar for groups A, B, and C (27%, 31%, and 19%,
      respectively). In the gestational hypertensive group the incidence of SGA infants
      was similar for groups A, B, and C (14%, 11%, and 12% respectively). CONCLUSIONS:
      The preeclamptic primigravid primiparous and multigravid primiparous groups
      behaved similarly in their clinical expression of hypertensive complications but
      differed from the multiparous group by having a higher incidence of HELLP
      syndrome. The incidence of complications in hypertensive pregnant women varied by
      parity but not by gravidity. The gestational hypertensive groups did not differ
      in their clinical expression of hypertensive complications.

PMID- 12196856
TI  - Cervical cancer during pregnancy.
AB  - Cervical cancer is one of the most devastating conditions that can complicate a
      pregnancy. Stage for stage, treatment for squamous cell cervical cancer is the
      same as that given in the non-pregnant patient. Radical surgery is the treatment
      of choice for the early stages of the disease. Although a planned delay in
      therapy may be considered for up to 20 weeks, for stages IA and IB1, it should be
      implemented cautiously and with the patient's full awareness of the risks. If
      delay is considered for higher stages, the patient must be aware of the paucity
      of data to support this plan. Chemoradiation is the standard treatment for
      advanced cancer of the cervix. When acceptable fetal maturity has been reached, a
      classical Caesarean section is usually performed prior to definitive treatment.

PMID- 12196857
TI  - Hemorrhagic shock.
AB  - OBJECTIVE: To review the clinical aspects of hemorrhagic shock and provide
      recommendations for therapy. OPTIONS: Early recognition of hemorrhagic shock and
      prompt systematic intervention will help avoid poor outcomes. OUTCOMES: Establish
      guidelines to assist in early recognition of hemorrhagic shock and to conduct
      resuscitation in an organized and evidence-based manner. EVIDENCE: Medline
      references were sought using the MeSH term "hemorrhagic shock." All articles
      published in the disciplines of obstetrics and gynaecology, surgery, trauma,
      critical care, anesthesia, pharmacology, and hematology between 1 January 1990
      and 31 August 2000 were reviewed, as well as core textbooks from these fields.
      Selected references from these articles and book chapters were also obtained and
      reviewed. The level of evidence has been determined using the criteria described
      by the Canadian Task Force on the Periodic Health Examination. RECOMMENDATIONS:
      1. Clinicians should be familiar with the clinical signs of hemorrhagic shock.
      (III-B) 2. Clinicians should be familiar with the stages of hemorrhagic shock.
      (III-B) 3. Clinicians should assess each woman's risk for hemorrhagic shock and
      prepare for the procedure accordingly. (III-B) 4. Resuscitation from hemorrhagic
      shock should include adequate oxygenation. (II-3A) 5. Resuscitation from
      hemorrhagic shock should include restoration of circulating volume by placement
      of two large-bore IVs, and rapid infusion of a balanced crystalloid solution. (I
      A) 6. Isotonic crystalloid or colloid solutions can be used for volume
      replacement in hemorrhagic shock (I-B). There is no place for hypotonic dextrose
      solutions in the management of hemorrhagic shock (I-E). 7. Blood component
      transfusion is indicated when deficiencies have been documented by clinical
      assessment or hematological investigations (II-2B). They should be warmed and
      infused through filtered lines with normal saline, free of additives and drugs
      (II-3B). 8. Vasoactive agents are rarely indicated in the management of
      hemorrhagic shock and should be considered only when volume replacement is
      complete, hemorrhage is arrested, and hypotension continues. They should be
      administered in a critical care setting with the assistance of a
      multidisciplinary team. (III-B) 9. Appropriate resuscitation requires ongoing
      evaluation of response to therapy, including clinical evaluation, and
      hematological, biochemical, and metabolic assessments. (III-B) 10. In hemorrhagic
      shock, prompt recognition and arrest of the source of hemorrhage, while
      implementing resuscitative measures, is recommended. (III-B)VALIDATION: These
      guidelines have been reviewed by the Clinical Practice Obstetrics Committee and
      approved by Executive and Council of the Society of Obstetricians and
      Gynaecologists of Canada. SPONSORS: The Society of Obstetricians and
      Gynaecologists of Canada.

PMID- 12196858
TI  - Hormone replacement therapy and breast cancer, revisited.

PMID- 12196859
TI  - Metformin and polycystic ovary syndrome: a literature review.
AB  - Polycystic ovary syndrome (PCOS) is a common endocrine condition that affects
      women of reproductive age. Anovulation, menstrual irregularities, hirsutism, and
      infertility are common clinical presentations. Long-term health concerns such as
      type II diabetes mellitus and, possibly, cardiovascular disease, have been linked
      to PCOS. Metformin, an oral hypoglycemic agent, has been recently advocated as
      treatment for some women with PCOS due to the association of PCOS with
      hyperinsulinemia. Metformin is utilized as sole therapy for ovulation induction
      as well as in combination with traditional ovulation-induction therapies. This
      review identified 23 prospective studies addressing the effects of metformin on
      PCOS. Because of the heterogeneity of the published reports, only a qualitative
      assessment of the data was possible. Review of this literature confirms a
      beneficial role of metformin in reducing insulin resistance in some women with
      PCOS. Other favourable biochemical effects include reduced free testosterone
      levels and increased sex hormone-binding globulin (SHBG). Metformin may improve
      menstrual regularity, leading to spontaneous ovulation, and improve ovarian
      response to conventional ovulation-induction therapies. There is, however, little
      evidence supporting the use of metformin to facilitate weight reduction, or
      improve serum lipids or hirsutism. Further evaluation is required to define the
      long-term effectiveness of metformin, who will benefit from metformin treatment,
      and the optimal duration of metformin therapy.

PMID- 12196860
TI  - Nitroglycerin as a uterine relaxant: a systematic review.
AB  - OBJECTIVE: To evaluate the effectiveness of nitroglycerin as a uterine relaxant
      for preterm labour, fetal extraction at Caesarean section, external version,
      embryo transfer, cervical dilation for first trimester pregnancy termination, and
      primary dysmenorrhea. DESIGN: A systematic review of randomized control trials
      (RCTs) of nitroglycerin in obstetrics and gynaecology. METHODS: We searched
      PubMed (1966-2001), the Cochrane Controlled Trials Register, and the
      International Journal of Obstetric Anesthesia using text terms
      quot:nitroglycerin," "glyceryl trinitrate," "uterus," "uterine," and
      "relaxation." The last search was conducted in January 2001. References from
      review articles and abstracts from major scientific meetings (1997-2000) were
      reviewed for relevant publications. RCTs comparing nitroglycerin to either
      placebo or another therapeutic intervention (ritodrine, magnesium sulphate, and
      prostaglandin) and whose quality score was equal to or greater than 2 were
      included (Class I evidence as described in the Report of the Canadian Task Force
      on the Periodic Health Exam). RESULTS: Sixty articles were retrieved of which 13
      were RCTs. Nitroglycerin was more effective for arresting preterm labour than
      placebo but not more effective when compared to ritodrine or magnesium.
      Nitroglycerin was not superior to placebo for uterine relaxation for either fetal
      extraction at Caesarean section or for external version. There were no
      differences in ease of embryo transfers when nitroglycerin spray was compared to
      placebo. In first trimester pregnancy terminations, less force was required to
      dilate the cervix when nitroglycerin was compared to no treatment. The incidence
      of preeclampsia was not reduced by nitroglycerin but fewer complications were
      noted when compared to the placebo group. In patients with primary dysmenorrhea,
      nitroglycerin significantly decreased pain. CONCLUSION: Although nitroglycerin is
      widely used, its superiority over currently used tocolytic agents is unproven.
      (Class C recommendation) Nitroglycerin has been demonstrated to decrease pain
      associated with dysmenorrhea. (Class A recommendation)

PMID- 12196861
TI  - Introducing printed postpartum orders for measles-mumps-rubella vaccination: a
      qualitative study.
AB  - OBJECTIVE: After introducing printed postpartum orders at our centre, we observed
      a large increase in measles-mumps-rubella (MMR) vaccination of susceptible women.
      The objective of this study was to ascertain factors responsible for the success
      of our approach and to identify potential obstacles so as to facilitate the
      implementation of similar policies at other hospitals. METHODS: For this
      qualitative study, taped semi-structured interviews were carried out with
      physicians, nurses, and a ward clerk regarding their views on postpartum MMR
      vaccination and on various aspects of implementing a printed postpartum order
      sheet that included MMR vaccination of susceptible women. Interviews were
      transcribed and the responses classified by theme. Thematic analysis was used to
      identify strengths and weaknesses of this approach. RESULTS: Following
      implementation of printed postpartum orders that included MMR vaccination of
      susceptible women, the proportion of eligible women vaccinated increased from
      12.1 to 81.7% (risk ratio 6.8, 95% confidence interval [CI] 3.3, 13.7). While the
      physician and nursing staff broadly supported this initiative, we identified the
      need for changes in obstetrical care and documentation: most importantly, a
      comprehensive protocol with supporting information and guidelines should be
      provided for postpartum nurses; and a system must be in place to ensure that the
      completed antenatal record, including screening test results, be available in the
      expected hospital of delivery by the late second trimester. CONCLUSION:
      Previously undocumented claims that standing orders for postpartum MMR
      vaccination will increase the rate of vaccination of susceptible women have now
      been substantiated at one centre. Nevertheless, careful infrastructure and
      systems changes are required to ensure implementation of such orders.

PMID- 12196862
TI  - The syndromic approach to treatment of sexually transmitted diseases in low
      income countries: issues, challenges, and future directions.
AB  - BACKGROUND: Sexually transmitted diseases (STDs) are a major cause of adult
      morbidity worldwide. In 1991, the World Health Organization (WHO) introduced the
      concept of the "syndromic approach" to managing sexually transmitted diseases in
      low-income countries, however, there has been some controversy regarding the
      ongoing use of this approach. OBJECTIVES: (1) To understand the use of the
      syndromic approach to managing sexually transmitted diseases in low-income
      countries, and to determine if evidence supports its continued use. (2) To help
      Canadian doctors understand the past STD management of immigrant patients from
      low-income countries, and evaluate the direct effect (if any) of such medical
      practices to the patient's health and perception of health in Canada. METHODS:
      Medline was searched under the key words "sexually transmitted diseases,"
      "developing nations," and "syndrome," as well as "algorithms," "prevention and
      control," and "WHO." Research articles and data were also accessed from the Web
      sites of WHO, UNAIDS, Reproductive Health Online (JHSPH), and the Centers for
      Disease Control and Prevention (USA). Data were selected based on the relevance
      to the topic, and research articles assessed from a methodological perspective.
      Most research articles were of Level II-2 evidence or lower as described using
      the Evaluation of Evidence criteria outlined in the Report of the Canadian Task
      Force on the Periodic Health Exam. RESULTS: In resource-poor countries, the use
      of the syndromic approach is appropriate for high-risk groups and for symptomatic
      individuals. However, it is still a poor screening approach when applied to
      asymptomatic cases, particularly in women. Risk scoring and simple laboratory
      tests help to increase the algorithmic sensitivity of the syndromic approach.
      CONCLUSION: Syndromic management involves making clinical decisions based on a
      patient's symptoms and signs. Until inexpensive, simple, and accurate STD
      diagnostics are developed and made available for use in low-income countries, a
      modified syndromic approach is the most feasible method of STD management in
      these countries. It is useful for Canadian physicians to be aware of this
      approach especially when caring for women from these countries.

PMID- 12196863
TI  - [Workshop on mental preparation and stress management: experience of residents
      finishing in obstetrics and gynecology].
AB  - The objective of this article is to report the experience of three graduating
      residents in Obstetrics and Gynecology at Laval University who were participants
      in a course on mental preparation and stress management. The students concluded
      that the experience has been very useful in preparation for the final specialty
      examination. They recommend that such a program be systematically evaluated
      before it is integrated in the residency program.

PMID- 12196864
TI  - Acquired hemophilia a presenting as a bleeding diathesis in a postpartum patient:
      diagnosis and management.
AB  - Antibodies against Factor VIII (FVIII) can develop in non-hemophiliac patients,
      causing the rare condition of acquired hemophilia. In 7.3% of the patients, the
      FVIII inhibitors appear either during pregnancy or in the postpartum period. In
      this case report, we present a non-hemophiliac patient, who presented five months
      postpartum with intermittent heavy vaginal bleeding, easy bruising, hemarthrosis,
      and recurrent frank hematuria. The woman presented to the emergency room with
      hematuria. Coagulation screening tests showed a prolonged APTT. Using a standard
      diagnostic algorithm, a Factor VIII inhibitor was detected. The treatment, cause
      of disease, and prognosis of this woman is presented in this paper as well as a
      literature review of acquired hemophilia A associated with pregnancy.

PMID- 12196865
TI  - Gestational trophoblastic disease.
AB  - OBJECTIVE: To provide standards for the diagnosis and treatment of patients with
      hydatidiform mole and gestational trophoblastic tumours (GTT). OPTIONS:
      Prognostic factors useful for treatment decisions in GTT are defined with
      patients classified as low-, medium-, and high-risk groups. OUTCOMES: Improved
      mortality and morbidity. EVIDENCE: Evidence was gathered using Medline for
      relevant studies and articles from 1980 to 2001 with specific reference to
      diagnosis, treatment options, and outcomes. The quality of evidence of
      Recommendations has been described using the Evaluation of Evidence criteria
      outlined in the Report of the Canadian Task Force on the Periodic Health Exam.
      RECOMMENDATIONS: 1. Suction curettage is the preferred method of evacuation of
      the hydatidiform mole (III-C). Post-operative surveillance with hCG assays is
      essential (II-3B). 2. Low-risk patients with both non-metastatic and metastatic
      disease should be treated with single-agent chemotherapy, either methotrexate or
      dactinomycin (II-3B). 3. Medium-risk patients should usually be treated with
      multi-agent chemotherapy, either MAC or EMA (III-C); single-agent chemotherapy
      may also be used (III-C). 4. High-risk patients should be treated with multi
      agent chemotherapy EMA/CO, with selective use of surgery and radiotherapy (II
      3B). Salvage chemotherapy with EP/EMA and surgery should be employed in resistant
      disease (III-C). 5. Placental site trophoblastic tumour that is non-metastatic
      should be treated with hysterectomy (III-C). Metastatic disease should be treated
      with chemotherapy, most commonly EMA/CO (III-C).6. Women should be advised to
      avoid pregnancy until hCG levels have been normal for six months following
      evacuation of a molar pregnancy and for one year following chemotherapy for
      gestational trophoblastic tumour. The combined oral contraceptive pill is safe
      for use by women with GTT (III-C). VALIDATION: These guidelines have been
      reviewed and approved by the Policy and Practice Guidelines Committee of the
      Society of Obstetricians and Gynaecologists of Canada (SOGC), the Gynaecologic
      Oncologists of Canada (GOC), the Society of Canadian Colposcopists (SCC), and by
      Executive and Council of the SOGC. SPONSOR: The Society of Obstetricians and
      Gynaecologists of Canada.

PMID- 12196866
TI  - Eyes and ears, hopes and fears.

PMID- 12196867
TI  - Utilization of preoperative urodynamic studies by Canadian gynaecologists.
AB  - OBJECTIVES: (1) To determine the proportion of Canadian gynaecologists who have
      urodynamic studies (UDS) readily available; (2) to assess the preoperative UDS
      utilization patterns of Canadian gynaecologists in various clinical scenarios of
      stress urinary incontinence (SUI). METHODS: A mail survey was sent to all 1266
      obstetrician/gynaecologist members of the Society of Obstetricians and
      Gynaecologists of Canada (SOGC), as part of an international survey with the
      U.K., U.S.A., New Zealand, and Australia. Survey questions included geographic
      availability of UDS and specific types of urodynamics testing available.
      Utilization of urodynamics prior to anti-incontinence surgery was assessed in
      four clinical scenarios: (A) a history of uncomplicated primary stress urinary
      incontinence, (B) a history of mixed stress and urgency incontinence, (C) stress
      incontinence with a history of straining to void, and (D) recurrent stress
      incontinence. RESULTS: Of the 1266 surveys mailed, 230 (18%) were returned. Forty
      four of the respondents did not manage incontinent women. Of the 186 respondents
      who did, 27% reported a special interest or additional postgraduate training in
      urogynaecology, and 73% were general gynaecologists. UDS were available in the
      same centre or city to 79% of respondents. For uncomplicated primary stress
      incontinence, 47% would always obtain preoperative UDS, 42% would not, and 11%
      would only if UDS were readily available. For the total group of respondents, in
      scenario A 47% would always obtain preoperative UDS, 42% would not, and 11% would
      only if UDS were readily available. Among general gynaecologists, in scenario A,
      if UDS were available in their city or centre of practice, 54% would always
      obtain preoperative UDS, as compared to 5% by general gynaecologists who did not
      have UDS available in their city or centre of practice. CONCLUSION: The data
      collected in this survey are compromised because of the low response rate.
      However, most (79%) of the respondents who manage women with urinary incontinence
      had access to urodynamics in the same centre or city. The utilization of
      urodynamics prior to surgical treatment of uncomplicated primary pure stress
      incontinence varies depending on the availability of such testing. An
      uncomplicated history of primary SUI and decreased availability of testing were
      two factors seen to have an effect of decreasing utilization of preoperative UDS.
      Hospital management did not always comply with SOGC guidelines for preoperative
      testing for SUI. Updating and dissemination of these guidelines is necessary to
      ensure "best" practice and highest quality of care for all women with SUI in
      Canada.

PMID- 12196868
TI  - Multiple versus single courses of antenatal corticosteroids for preterm birth: a
      pilot study.
AB  - OBJECTIVES: (1) To determine the feasibility of a multicentre, randomized, double
      masked, placebo-controlled trial to investigate the effects of multiple courses
      of antenatal corticosteroids (ACS), more than 7 days following the initial course
      of ACS therapy, on perinatal or neonatal mortality or neonatal morbidity. (2) To
      determine the risk of complications that would require discontinuation of ACS
      therapy. (3) To determine if multiple courses of ACS have an effect on the
      concentrations of plasma cortisol and adrenocorticotropin hormone (ACTH) in cord
      blood and in maternal blood immediately following delivery, compared to a single
      course of ACS. METHODS: Women at 24 to 30 weeks' gestation, at continued
      increased risk of preterm birth 7 or more days following a single course of ACS,
      were randomized to receive weekly courses of betamethasone or placebo until 33
      weeks' gestation or delivery. RESULTS: Women were recruited at two hospitals in
      Toronto from 01 September 1999 to 31 August 2000. Of the 78 women who were
      approached and were eligible for the study, 12 (15%) were recruited and 66 (85%)
      refused to participate. Of the 66 refusals, 38 (58%) did not feel their
      physicians were supportive of the study, 10 (15%) did not want to be randomized,
      and 4 (6%) had other personal reasons for refusing to enter the trial. Fourteen
      women (21%) had physicians who did not allow them to join the study. The lack of
      physician support was due to concerns related to the potential adverse effects of
      multiple courses of ACS. There were no complications requiring discontinuation of
      ACS. Plasma cortisol and ACTH concentrations in cord and maternal blood taken
      after delivery were not significantly different between ACS and placebo groups.
      CONCLUSION: A multicentre randomized controlled trial is required to determine
      the benefits and risks of multiple versus a single course of ACS. If the study
      protocols are supported by physicians and their patients, a multicentre
      randomized controlled trial is feasible.

PMID- 12196869
TI  - Do we use too much antenatal betamethasone?
AB  - OBJECTIVE: To review and rationalize the liberal use of antenatal betamethasone
      in the setting of threatened preterm birth. STUDY DESIGN: A retrospective review
      was performed using the charts of all patients at Ste-Justine Hospital, Montreal
      QC, who received antenatal betamethasone between 01 April 1997 and 31 March 1998.
      Initial treatment consisted of 2 doses of 12 mg IM given 24 hours apart. Repeat
      doses of 12 mg weekly were administered at the discretion of the treating
      physician. Optimal antenatal betamethasone therapy was defined as delivery within
      1 week of initial treatment, prior to 34 weeks. Aside from number and timing of
      doses, other factors analyzed included: gestational age at admission and
      delivery, diagnosis associated with threatened preterm birth (PTB), number of
      hospital admissions, and delay between re-admission and delivery. RESULTS: Of the
      334 patients identified, 82 (25%) received optimal treatment. Of the remaining
      252 patients, 204 (81%) received repeat doses. In the repeat dose group, 112
      (55%) women delivered after 34 weeks, while 70 of the 92 remaining patients were
      hospitalized until delivery. The other 22 patients who received serial doses were
      discharged at least once prior to delivery; of these patients, 8 were re-admitted
      more than 24 hours pre-delivery (i.e., adequate time for re-treatment), while 14
      were not, but only 6 of these were delivered urgently. Thus, a maximum of 60
      patients (25% of repeat doses) could potentially have benefited from this
      approach. Of the 48 patients not receiving repeat doses, 37 (77%) delivered after
      34 weeks. Five remained hospitalized, and 6 were discharged prior to delivery and
      re-admitted (2 patients > 24 hr and 4 patients < 24 hr from delivery). This
      represented a potential underutilization of betamethasone by 3% (11/334) of the
      patients, but only 1.8% (6/334) were of less than 32 weeks' gestation.
      CONCLUSION: This study demonstrated the difficulty in predicting which of the
      patients presenting with threatened preterm birth would actually go on to deliver
      during the window of benefit of antenatal betamethasone therapy. Our desire to
      permit all premature fetuses to profit from the positive effects of this therapy
      must be balanced by a reserve in exposing too many to too much. Use of antenatal
      betamethasone in our unit has significantly decreased since this review.

PMID- 12196870
TI  - Fetal health surveillance in labour.
AB  - OBJECTIVE: This guideline defines the standards pertaining to the application and
      documentation of fetal surveillance in labour that will decrease the incidence of
      birth asphyxia while maintaining the lowest possible rate of obstetrical
      intervention. Both high- and low-risk obstetrical populations are considered. It
      is intended that this guideline could be used by all persons providing
      intrapartum care in Canada, including nurses, physicians, and midwives. OPTIONS:
      Consideration has been given to methods of fetal surveillance currently available
      in Canada, including intermittent auscultation, electronic fetal monitoring
      (alone and when paired with vibro-acoustic or scalp stimulation and fetal scalp
      blood sampling), the "admission strip," computerized heart rate analysis, fetal
      oxygen saturation monitoring, fetal electrocardiogram analysis, and near-infrared
      spectroscopy. OUTCOMES: Short- and long-term outcomes were considered that may
      indicate the presence of birth asphyxia. The associated rates of operative or
      other labour interventions were also considered. EVIDENCE: A comprehensive review
      of randomized controlled trials performed from 1995 to date and a search of the
      literature using Medline and the Cochrane Database of all new studies on fetal
      surveillance. The level of evidence has been determined using the criteria
      described by the Canadian Task Force on the Periodic Health Examination.
      RECOMMENDATIONS: Part I: Standard Fetal Surveillance in Labour 1. Women in active
      labour should receive continuous close support from an appropriately trained
      professional. One-to-one nursing is recommended. (I-A)2. Intermittent
      auscultation following an established protocol of surveillance and response
      (Figure 1) is the preferred method of fetal surveillance in healthy pregnancies
      in the active phase of labour. (I-A). 3. Labour induction requires close
      monitoring of uterine activity and fetal heart rate. (III-B). 4. In the presence
      of abnormal fetal heart rate characteristics detected by intermittent
      auscultation and unresponsive to resuscitative measures, increased surveillance
      by continuous electronic fetal monitoring or fetal scalp sampling or delivery
      should be instituted. (I-A). 5. Continuous intrapartum electronic fetal
      monitoring is recommended: a) for pregnancies where there is an increased risk of
      perinatal death, cerebral palsy, or neonatal encephalopathy (III-C) b) when
      oxytocin is being used for augmentation of labour (1-A) c) when oxytocin is being
      used for induction of labour (III-C). 6. With respect to continuous electronic
      fetal monitoring, all professionals must be familiar with the paper speed used in
      each case to avoid misinterpretation. The correct time should be recorded on the
      electronic fetal monitoring record. (III-C). 7. Electronic fetal monitoring
      records should be inspected and documented every 15 minutes in the active phase
      of labour and at least every 5 minutes in the second stage of labour. (III-C). 8.
      The timing of electronic fetal monitoring patterns should be determined in
      association with uterine contractions. The contraction frequency, duration,
      intensity, and resting tone should be assessed and documented. Abdominal
      palpation, a tocodynamometer, or an intrauterine pressure catheter may be used to
      facilitate the assessment. (III-C). 9. Practitioners should use standard
      terminology when describing fetal heart rate characteristics of an electronic
      fetal monitoring record. (III-C)10. Fetal scalp blood sampling is recommended in
      association with electronic fetal monitoring patterns that are uninterpretable or
      non-reassuring, such as sustained minimal or absent variability, uncorrectable
      late decelerations, increasing fetal tachycardia, and abnormal FHR
      characteristics on auscultation. (II-3B). 11. The limited knowledge available on
      the use of labour admission tests warrants further research to establish the
      usefulness of this screening approach. (III-C)Part II: New Technologies for Fetal
      Surveillance in Labour. 12. The use of computer-based algorithms alone to
      interpret fetal heart rate patterns is not recommended as a standard of care at
      the present time. (III-D). 13. Fetal pulse oximetry as an adjunct to electronic
      fetal heart monitoring in patients with non-reassuring FHR status is not
      recommended as a standard of care at the present time. (III-D)14. ST waveform
      analysis technology is under development but is not recommended as a standard of
      care at this time. (III-C)15. Near-infrared spectroscopy as an adjunct to
      electronic fetal monitoring is currently not recommended as there is insufficient
      evidence to assess its efficacy in fetal surveillance. (III-D)16. Further study
      of fetal pulse oximetry, ST waveform analysis, and near-infrared technology in
      clinical research settings is encouraged. (III-B)VALIDATION: This guideline was
      reviewed by the SOGC Clinical Practice Obstetrics Committee, Maternal Fetal
      Medicine Committee, and ALARM Committee, as well as by the Canadian Medical
      Protective Association. SPONSOR: The Society of Obstetricians and Gynaecologists
      of Canada.

PMID- 12196871
TI  - There is no gene for the human spirit.

PMID- 12196872
TI  - Laparoscopic bowel injuries: forty litigated gynaecological cases in Canada.
AB  - OBJECTIVE: To review the clinical circumstances and the clinical and legal
      outcomes of 40 laparoscopic bowel injuries that were litigated in Canada. DESIGN:
      Retrospective review of 40 litigated cases of laparoscopic bowel injury, from
      1990 to the end of 1998, provided by the Canadian Medical Protective Association
      (CMPA). MEASUREMENTS AND MAIN RESULTS: The laparoscopy was performed for
      diagnosis (n = 13), tubal occlusion (n = 15), and as an operative therapeutic
      procedure (n = 12). Injuries were related to the initial peritoneal entry in 22
      (55%) women (19 during the closed technique and 3 with the open technique). Of
      these, the injury was due to the primary trocar (n = 17), scalpel (n = 1), Veress
      needle (n = 1), Veress needle or undetermined (n = 2), and fascial suture (n =
      1). The small bowel was injured in 9 of 11 entries by the trocar during
      diagnostic laparoscopy and in 6 of 14 tubal occlusions. Five injuries in the
      tubal occlusion group were attributed to "cautery." The injury was recognized
      intra-operatively in 55% of cases. The clinical outcome was uncomplicated in 85%
      of patients. There was no difference in clinical outcome between small versus
      large bowel injuries and between intra-operative versus post-operative diagnosis
      of the injury. The litigation outcome was favourable to the physician in 75% of
      cases. Recognition was delayed in 45% of cases and this was associated with 67%
      of the litigation outcomes unfavourable to physicians. CONCLUSIONS: (1) The
      initial laparoscopic entry into the peritoneal cavity remains the major
      contributor to bowel injury in laparoscopic surgery. (2) The open (Hasson)
      technique does not prevent bowel injuries. (3) Delayed recognition was a major
      factor in assessment of liability.

PMID- 12196873
TI  - Maternal cell contamination of amniotic fluid samples obtained by open needle
      versus trocar technique of amniocentesis.
AB  - OBJECTIVE: To determine the incidence of maternal cell contamination (MCC) in the
      open-needle amniocentesis sampling technique compared with the trocar-in-place
      technique. METHODS: A retrospective analysis was conducted on 2,498 mid-trimester
      amniocenteses performed in two tertiary care centres in Canada. The University of
      Alberta centre used the open-needle (without the trocar) technique and the
      University of British Columbia centre used the standard (with the trocar in
      place) technique. Data were gathered regarding the nature of the amniotic fluid,
      number of needle passes, amniocentesis results, and the occurrence of maternal
      cell contamination. The statistical analysis used logistic regression, and
      controlled for the potential confounders of bloody fluid taps and requirement for
      more than one needle insertion. RESULTS: The incidence of maternal cell
      contamination was 1.16% with the open-needle technique and 0.78% with the
      standard trocar-in-place technique (p < 0.315), with a power of 42%. CONCLUSION:
      The data suggested there is no significant increase in maternal cell
      contamination with the open-needle versus trocar-in-place techniques of
      amniocentesis. However, the small sample size, combined with the low prevalence
      of the outcome of interest (MCC), provides insufficient power to draw firm
      conclusions about the difference in MCC between the two techniques.

PMID- 12196874
TI  - Canadian physicians' role in contraception from the 19th century to now.
AB  - Birth control techniques were widely available in 19th-century Canada, despite
      the fact that they were illegal. Most physicians remained silent about
      contraception, with a small minority vocally opposed to the practice of birth
      control. Canadian physicians were influenced by the social, economic, legal, and
      political values of their time, and their support of birth control initially
      lagged far behind public interest and need. At later points in Canadian medical
      history, physicians actively supported increased access to contraceptive
      services, and played a significant role in the legalization of contraception in
      this country. The Canadian birth control movement made tremendous strides in the
      1930s with the dissemination of contraceptive information to the public and the
      opening of the first public birth control clinic. The Canadian Medical
      Association supported contraceptive practice as part of preventive medicine in
      the 1930s, and the legalization of contraception in the early and mid 1960s.
      Contraception was formally legalized in Canada in 1969 and has become a
      significant aspect of medical practice. In Canada, current medical controversies
      in contraception include issues of public education, advertising, contraceptive
      research, and the integration of contraception with other aspects of reproductive
      and sexual health in medical practice.

PMID- 12196875
TI  - Benign multicystic mesothelioma: a case report.
AB  - Benign multicystic mesothelioma (also known as multilocular peritoneal inclusion
      cyst) is a rare lesion found on any abdominal peritoneal surface that occurs most
      frequently in premenopausal women. We report the case of a 36-year- old woman,
      who presented with a history of generalized abdominal pain, intermittent
      abdominal bloating, and episodes of loose stools. A pelvic ultrasound revealed a
      complex cystic mass with fine internal septations. The patient was managed by
      laparotomy with removal of mass, total abdominal hysterectomy, bilateral salpingo
      oophorectomy, omentectomy, and multiple peritoneal biopsies. Final pathology
      revealed benign multicystic mesothelioma. Although mesothelioma is a rare tumour,
      it is important for all gynaecologists to recognize its existence, the appearance
      of this lesion, and its generally benign course. This is especially important as
      it occurs in young women where fertility considerations must be part of the
      discussion of any pelvic surgery.

PMID- 12196876
TI  - Fetal health surveillance in labour.
AB  - OBJECTIVE: This guideline defines the standards pertaining to the application and
      documentation of fetal surveillance in labour that will decrease the incidence of
      birth asphyxia while maintaining the lowest possible rate of obstetrical
      intervention. Both high- and low-risk obstetrical populations are considered. It
      is intended that this guideline could be used by all persons providing
      intrapartum care in Canada, including nurses, physicians, and midwives. OPTIONS:
      Consideration has been given to methods of fetal surveillance currently available
      in Canada, including intermittent auscultation, electronic fetal monitoring
      (alone and when paired with vibro-acoustic or scalp stimulation and fetal scalp
      blood sampling), the "admission strip," computerized heart rate analysis, fetal
      oxygen saturation monitoring, fetal electrocardiogram analysis, and near-infrared
      spectroscopy. OUTCOMES: Short- and long-term outcomes were considered that may
      indicate the presence of birth asphyxia. The associated rates of operative or
      other labour interventions were also considered. EVIDENCE: A comprehensive review
      of randomized controlled trials performed from 1995 to date and a search of the
      literature using Medline and the Cochrane Database of all new studies on fetal
      surveillance. The level of evidence has been determined using the criteria
      described by the Canadian Task Force on the Periodic Health Examination.
      RECOMMENDATIONS: Part I: Standard Fetal Surveillance in Labour 1. Women in active
      labour should receive continuous close support from an appropriately trained
      professional. One-to-one nursing is recommended. (I-A) 2. Intermittent
      auscultation following an established protocol of surveillance and response
      (Figure 1) is the preferred method of fetal surveillance in healthy pregnancies
      in the active phase of labour. (I-A) 3. Labour induction requires close
      monitoring of uterine activity and fetal heart rate. (III-B) 4. In the presence
      of abnormal fetal heart rate characteristics detected by intermittent
      auscultation and unresponsive to resuscitative measures, increased surveillance
      by continuous electronic fetal monitoring or fetal scalp sampling or delivery
      should be instituted. (I-A) 5. Continuous intrapartum electronic fetal monitoring
      is recommended: a) for pregnancies where there is an increased risk of perinatal
      death, cerebral palsy, or neonatal encephalopathy (III-C) b) when oxytocin is
      being used for augmentation of labour (1-A) c) when oxytocin is being used for
      induction of labour (III-C). 6. With respect to continuous electronic fetal
      monitoring, all professionals must be familiar with the paper speed used in each
      case to avoid misinterpretation. The correct time should be recorded on the
      electronic fetal monitoring record. (III-C) 7. Electronic fetal monitoring
      records should be inspected and documented every 15 minutes in the active phase
      of labour and at least every 5 minutes in the second stage of labour. (III-C) 8.
      The timing of electronic fetal monitoring patterns should be determined in
      association with uterine contractions. The contraction frequency, duration,
      intensity, and resting tone should be assessed and documented. Abdominal
      palpation, a tocodynamometer, or an intrauterine pressure catheter may be used to
      facilitate the assessment. (III-C) 9. Practitioners should use standard
      terminology when describing fetal heart rate characteristics of an electronic
      fetal monitoring record. (III-C) 10. Fetal scalp blood sampling is recommended in
      association with electronic fetal monitoring patterns that are uninterpretable or
      non-reassuring, such as sustained minimal or absent variability, uncorrectable
      late decelerations, increasing fetal tachycardia, and abnormal FHR
      characteristics on auscultation. (II-3B) 11. The limited knowledge available on
      the use of labour admission tests warrants further research to establish the
      usefulness of this screening approach. (III-C) Part II: New Technologies for
      Fetal Surveillance in Labour 12. The use of computer-based algorithms alone to
      interpret fetal heart rate patterns is not recommended as a standard of care at
      the present time. (III-D) 13. Fetal pulse oximetry as an adjunct to electronic
      fetal heart monitoring in patients with non-reassuring HR status is not
      recommended as a standard of care at the present time. (III-D) 14. ST waveform
      analysis technology is under development but is not recommended as a standard of
      care at this time. (III-C) 15. Near-infrared spectroscopy as an adjunct to
      electronic fetal monitoring is currently not recommended as there is insufficient
      evidence to assess its efficacy in fetal surveillance. (III-D) 16. Further study
      of fetal pulse oximetry, ST waveform analysis, and near-infrared technology in
      clinical research settings is encouraged. (III-B) VALIDATION: This guideline was
      reviewed by the SOGC Clinical Practice Obstetrics Committee, Maternal Fetal
      Medicine Committee, and ALARM Committee, as well as by the Canadian Medical
      Protective Association. SPONSOR: The Society of Obstetricians and Gynaecologists
      of Canada.

PMID- 12196877
TI  - New opportunities to preserve fertility in cancer treatment.

PMID- 12196878
TI  - Ultrasonographic assessment of endometrial thickness: a review.
AB  - Measurement of endometrial thickness with ultrasonography is a modality commonly
      used today. Its clinical importance and applications extend throughout the phases
      of the reproductive lives of women. In premenopausal women, endometrial thickness
      is used to monitor infertility treatment, while in postmenopausal women with
      abnormal uterine bleeding it is useful as an initial investigation for
      endometrial hyperplasia or cancer. Moreover, endometrial thickness can vary with
      the menstrual cycle and with the use of hormone replacement therapy or selective
      estrogen receptor modulators. In this review, the use of ultrasound to measure
      both the premenopausal and postmenopausal endometrium is discussed.

PMID- 12196879
TI  - Birth weight by gestational age for Albertan liveborn infants, 1985 through 1998.
AB  - OBJECTIVES: (1) To provide percentile tables and graphs of birth weight by
      gestational age and by gender, for singleton and twin liveborn neonates. (2) To
      determine changes in birth weight relative to gestational age over the study
      period. METHODS: Data on 556,775 singletons and 12,125 twins, born alive in
      Alberta from 1985 through 1998, were obtained from Alberta Registries - Vital
      Statistics. Mean birth weights for individual and grouped years were compared by
      independent two-tailed t-tests. Linear trends in birth weight over the 14-year
      period were obtained using one-way analyses of variance. RESULTS: Four tables and
      corresponding graphs showing birth weight for gestational age by gender for 21
      through 44 completed weeks gestation provide data for the 1st to 99th percentile.
      Changes in birth weight for the combined gestational ages included an increase
      for singletons (male, F 17.6, p < 0.001; female, F 53.3, p < 0.001), and a
      decrease for female twins (F 5.8, 0.004). The increase for singletons was seen at
      38 through 42 weeks gestation for both genders. No change occurred under 38 weeks
      except in singleton females of 33 to 35 weeks with a decrease in birth weight
      observed from 2636 +/- 539 g, 1985 to 2576 +/- 479 g, 1998; t 2.5, p = 0.002.
      CONCLUSIONS: The graphs and tables established in this study represent a specific
      geographic area and population. They may be relevant as a reference for other
      geographic regions and populations. The clinical significance of the observed
      increased birth weight among term, but not preterm newborns, requires critical
      evaluation.

PMID- 12196880
TI  - Randomized controlled trial of rectal misoprostol versus oxytocin in third stage
      management.
AB  - OBJECTIVE: To compare rectal misoprostol with oxytocin for routine management of
      the third stage of labour. STUDY DESIGN: A total of 240 parturient women were
      randomized, at three University of Toronto teaching hospitals, to receive either
      rectal misoprostol (400 microg) after delivery of the infant or parenteral
      oxytocin (5 units i.v. or 10 units i.m.) with the delivery of the anterior
      shoulder, when possible, or 5 units i.v. or i.m after the delivery of the
      placenta. The primary outcome measure was change in hemoglobin (Delta[Hgb]) from
      admission in early labour to day one postpartum. SETTING: The labour ward of
      three University of Toronto teaching hospitals: St. Michael's, Toronto General,
      and Mount Sinai. POPULATION: Labouring women either nulliparous or multiparous
      with no known risk for excessive third stage blood loss; vertex presentation; no
      previous Caesarean delivery; induced, spontaneous, or augmented labour. RESULTS:
      No difference in Delta[Hgb] was observed between the two groups; the Delta[Hgb]
      in the oxytocin and misoprostol groups were 1.43 g/L (95% confidence interval
      [CI], 1.2-1.6 g/L) and 1.59 g/L (95% CI, 1.4-1.8 g/L) respectively (p = 0.35).
      Secondary outcome measures (excessive third stage bleeding, duration of third
      stage of labour, need for manual removal of the placenta or the need for
      additional oxytocics) did not differ between the two groups. CONCLUSION: Rectal
      misoprostol is of equivalent efficacy to parenteral oxytocin for the prevention
      of primary postpartum hemorrhage. Rectal misoprostol is an appropriate uterotonic
      agent for routine management of the third stage of labour.

PMID- 12196881
TI  - Human embryonic stem cell lines: the ethics of derivation.
AB  - In Canada it is permissible to proceed with stem cell research using human
      embryos created by in vitro fertilization (IVF) provided: these were originally
      created for infertility treatment; they are no longer required for such
      treatment; and there is an appropriate consent for their research use. As such,
      IVF human embryos in excess of clinical need are a valuable resource for
      embryonic stem cell researchers. A point often overlooked, however, is that these
      excess IVF human embryos are also a scarce resource. Their scarcity suggests the
      need to develop sound policies and procedures, in a timely and coordinated
      fashion, to ensure that the few human embryos available for embryonic stem cell
      research are not used in less important research endeavours or used when other
      biological materials are appropriate. Injudicious use of the few human embryos
      available for research use may risk the following consequences: no ongoing
      research in Canada to derive human embryonic stem cell lines; a reliance on the
      importation of stem cell lines from other countries for any research on the use
      of embryonic stem cells; and pressure from Canadian researchers to remove the
      prohibition on the purposeful creation of human embryos for research use.

PMID- 12196882
TI  - Breast cancer, pregnancy, and breastfeeding.
AB  - OBJECTIVE: The primary objective of this guideline is to provide Canadian
      physicians up-to-date, accurate information and recommendations regarding: i)
      impact of pregnancy and lactation on risk of breast cancer; ii) prognosis of
      breast cancer diagnosed during pregnancy and lactation; iii) risk of recurrence
      of breast cancer with the occurrence of subsequent pregnancies; iv) feasibility
      of breastfeeding and its impact on the prognosis of women with breast cancer.
      OPTIONS: This guideline reviews evidence on whether pregnancy and breastfeeding
      change the lifetime risk for breast cancer in women, and whether breast cancer
      diagnosed during pregnancy or during lactation has a different prognosis. It
      offers the clinician advice on the diagnostic options to help identify breast
      cancer in pregnancy and/or during lactation, and offers evidence-based
      recommendations in managing an ongoing pregnancy and/or lactation when treatment
      for breast cancer is being planned. It also offers recommendations to clinicians
      in counselling their patients regarding future pregnancy and future breastfeeding
      for women who have been treated for breast cancer. OUTCOMES: These guidelines
      should help physicians counsel patients using evidence-based recommendations.
      These recommendations may also improve the prognosis of patients diagnosed with
      breast cancer during pregnancy and lactation, or of those patients who had breast
      cancer and are contemplating future pregnancies. EVIDENCE: A Medline search was
      carried out for all publications from 1990 through 2000, in the English language,
      related to breast cancer and pregnancy in terms of diagnosis, prognosis, and
      treatment, as well as for breast cancer and breastfeeding, with particular focus
      on impact of treatment of breast cancer on lactation and prognosis of breast
      cancer after lactation. The authors submitted the manuscript for review to
      members of the Breast Disease Committee, who also validated the levels of
      evidence. The final manuscript was submitted to the SOGC Council for approval and
      dissemination. The levels of evidence for recommendations have been determined
      using the criteria described by the Canadian Task Force on the Periodic Health
      Examination. BENEFITS, HARMS, AND COSTS: Canadian physicians will be able to
      counsel their patients on the impact of pregnancy and lactation on a woman's
      lifetime risk for breast cancer. Physicians and patients will be empowered to
      decide how to manage pregnancy and lactation when breast cancer is diagnosed in
      pregnancy, and to appreciate the ramifications of reproduction and breastfeeding
      after breast cancer. This guideline identifies areas where good evidence is
      lacking and advocates research in those areas. RECOMMENDATIONS: Women should be
      counselled regarding their risk for breast cancer and be informed that: 1. There
      is good evidence that there is a transient increase in risk of breast cancer in
      the first three to four years after delivery of a singleton baby (II-2B).
      Subsequently, their lifetime risk seems lower than that of women who remain
      nulliparous (II-2B). 2. There is good evidence that the risk for premenopausal
      breast cancer is reduced with lactation (II-2A). This protective effect seems to
      be best for women who had extended periods of breastfeeding during their lifetime
      (ll-2B). Women with familial risks could potentially benefit most from
      breastfeeding (II-2C). Since breast milk is the ideal nutrient for the newborn,
      and since breastfeeding is a modifiable risk factor, all women should be
      encouraged to breastfeed their children (II-2A). 3. All women should be
      encouraged to practice breast self-examination in pregnancy and during lactation
      (II-2B). Clinicians should screen all pregnant patients for breast cancer with
      thorough breast examination early in pregnancy (III-B). The clinician is advised
      to examine the breast in the postpartum period if the woman is not breastfeeding.
      The obstetrician is advised to examine the breast at any time in the postpartum
      period if the woman presents with breast symptoms (III-B). 4. Physicians should
      be encouraged to use ultrasltrasonography, mammography, needle aspiration, or
      breast biopsies to assess suspicious breast masses in pregnancy and during
      lactation, in the same timely fashion as for non-pregnant or non-lactating women
      (II-2A). Interruption of lactation during investigation is not necessary, nor is
      it recommended unless nuclear studies are entertained (III-B). 5. Once breast
      cancer is diagnosed, a multidisciplinary approach should be taken. This includes
      the obstetrician, surgeons, medical and radiation oncologists, and breast cancer
      counsellors (II-2A). 6. In early pregnancy, the patient should be counselled
      regarding the effect of proposed therapy on the fetus and on overall maternal
      prognosis. Termination of pregnancy should be discussed, but the patient should
      be counselled that prognosis is not altered by termination of pregnancy. Women
      should be advised that premature menopause may result from breast cancer
      treatments, especially if chemotherapy is given to patients who are past the age
      of 30. (II-2C) 7. Up until now, modified radical mastectomy was the cornerstone
      of surgical treatment of breast cancer during pregnancy. Adjuvant chemotherapy
      should be entertained and, if required, administered without delay. The patient
      should be counselled regarding the effect of chemotherapy on the fetus and/or the
      future reproductive potential of the patient (II-2B). In the third trimester, the
      risks and benefits of early delivery versus continuation of pregnancy, and the
      effect of chemotherapy on the fetus, should be addressed (II-2B). Women
      undergoing chemotherapy or tamoxifen treatment should not breastfeed (III-B). 8.
      Women treated for breast cancer and who wish to become pregnant should be
      counselled that pregnancy is possible and does not seem to be associated with a
      worse prognosis for their breast cancer (II-3C). However, they should be made
      aware that the evidence to support such advice is relatively poor. 9. Since most
      breast cancer recurrences appear within two to three years after initial
      diagnosis, patients should be advised to postpone pregnancy for three years (III
      C). If a patient has axillary node involvement, the recommendation to defer
      pregnancy should be extended to five years, but this recommendation is based on
      opinion only (III-C). Prior to attempting pregnancy, a breast cancer survivor
      should be referred for a full oncologic evaluation. 10. There is no evidence that
      breastfeeding increases the risk of breast cancer recurring or of a second breast
      cancer developing, nor that it carries any health risk to the child. Women
      previously treated for breast cancer, who do not show any evidence of residual
      tumour, should be encouraged to breastfeed their children (III-B). VALIDATION:
      Level of evidence, quality of research in the recruited publications, and ensuing
      recommendations were reviewed and discussed by members of the SOGC Breast Disease
      Committee as well as by a member of the Gynaecological Oncology Committee.
      External reviewers with expertise in the area were also solicited for comments
      and criticism.

PMID- 12196883
TI  - More than a brief and shining moment, Mr. Romanow.

PMID- 12196884
TI  - Toward a family-building approach to donor insemination.
AB  - Donor insemination (DI) is the oldest and simplest method of "treating" male
      infertility. The medical profession, prospective parents, legislators, and
      society in general are increasingly recognizing that providing DI services
      involves far more than facilitation of conception. This paper explores a
      multidisciplinary family-building approach to DI as an alternative to a treatment
      of-infertility approach, and describes the need to provide patients with a
      broader and deeper preparation for this special type of parenthood. The short
      term medical ease of the procedure is contrasted with the complexity and
      seriousness of the long-term social and psychological issues generated for the
      gamete provider, the recipient couple, and the offspring by the secrecy
      surrounding the procedure.

PMID- 12196885
TI  - Solvent abuse in pregnancy: a perinatal perspective.
AB  - OBJECTIVE: To review the scope and sequelae of solvent abuse in women presenting
      to a Manitoba teaching hospital. METHODS: Fifty-six patient charts with a
      diagnosis of solvent abuse in pregnancy were identified through computer search
      in the medical records of Winnipeg Health Sciences Centre, General Hospital.
      These charts were reviewed and data obtained from birthing records and associated
      pediatric charts. RESULTS: Renal tubular acidosis was diagnosed in three patients
      (5.3%). Two patients (3.6%) had adverse neurological sequelae. One patient was
      diagnosed with brain damage, including expressive aphasia. Twelve patients
      (21.4%) delivered preterm infants. Nine infants (16.1%) had major anomalies.
      Seven infants (12.5%) had fetal alcohol syndrome (FAS)-like facial features. Six
      neonates (10.7%) had hearing loss. CONCLUSION: Substance abuse in pregnancy is
      associated with severe maternal and neonatal sequelae. Physicians must be aware
      of this increasing problem in the obstetrical population and assistance should be
      offered to each woman, ideally before a woman becomes pregnant, but at least at
      the first contact a pregnant woman makes with the health care community.

PMID- 12196886
TI  - Endometriosis causing cyclic compression of the right external iliac vein with
      cyclic edema of the right leg and thigh.
AB  - A case report of endometriosis encircling the right external iliac vein, causing
      catamenial edema of the right leg and thigh, is presented. Successful surgical
      treatment is described. A literature review of extraperitoneal endometriosis will
      further the reader's awareness of unusual presentations of endometriosis.

PMID- 12196887
TI  - SOGC clinical guidelines. Hysterectomy.
AB  - OBJECTIVE: To identify the indications for hysterectomy, preoperative assessment,
      and available alternatives required prior to hysterectomy. Patient self-reported
      outcomes of hysterectomy have revealed high levels of patient satisfaction. These
      may be maximized by careful preoperative assessment and discussion of other
      treatment choices. In most cases hysterectomy is performed to relieve symptoms
      and improve quality of life. The patient's preference regarding treatment
      alternatives must be considered carefully. OPTIONS: The areas of clinical
      practice considered in formulating this guideline are preoperative assessment
      including alternative treatments, choice of method for hysterectomy, and
      evaluation of risks and benefits. The risk-to-benefit ratio must be examined
      individually by the woman and her health practitioners. OUTCOMES: Optimizing the
      decision-making process of women and their caregivers in proceeding with a
      hysterectomy having considered the disease process, and available alternative
      treatments and options, and having reviewed the risks and anticipated benefits.
      EVIDENCE: Using Medline, PubMed, and the Cochrane Database, English language
      articles were reviewed from 1996 to 2001 as well as the review published in the
      1996 SOGC guidelines. The level of evidence has been determined using the
      criteria described by the Canadian Task Force on the Periodic Health Examination.
      BENEFITS, HARMS, AND COSTS: Hysterectomy is the treatment of choice for certain
      gynaecologic conditions. The predicted advantages must be carefully weighed
      against the possible risks of the surgery and other treatment alternatives. In
      the properly selected patient, the result from the surgery should be an
      improvement in the quality of life. The cost of the surgery to the health care
      system and to the patient must be interpreted in the context of the cost of
      untreated conditions. The approach selected for the hysterectomy will impact on
      the cost of the surgery. RECOMMENDATIONS: Benign Disease 1. Leiomyomas: For
      symptomatic fibroids, hysterectomy provides a permanent solution to menorrhagia
      and the pressure symptoms related to an enlarged uterus. (I-A) 2. Abnormal
      uterine bleeding: Endometrial lesions must be excluded and medical alternatives
      should be considered as a first line of therapy. (III-B) 3. Endometriosis:
      Hysterectomy is often indicated in the presence of severe symptoms with failure
      of other treatments and when fertility is no longer desired. (1-B) 4. Pelvic
      relaxation: A surgical solution usually includes vaginal hysterectomy, but must
      include pelvic supporting procedures. (II-B) 5. Pelvic pain: A multidisciplinary
      approach is recommended, as there is little evidence that hysterectomy will cure
      chronic pelvic pain. When the pain is confined to dysmenorrhea or associated with
      significant pelvic disease, hysterectomy may offer relief. (II-C) Preinvasive
      Disease 1. Hysterectomy is usually indicated for endometrial hyperplasia with
      atypia. (I-A) 2. Cervical intraepithelial neoplasia in itself is not an
      indication for hysterectomy. (I-B) 3. Simple hysterectomy is an option for
      treatment of adenocarcinoma in situ of the cervix when invasive disease has been
      excluded. (I-B) Invasive Disease 1. Hysterectomy is an accepted treatment or
      staging procedure for endometrial carcinoma. It may play a role in the staging or
      treatment of cervical, epithelial ovarian, and fallopian tube carcinoma. (I-A)
      Acute Conditions 1. Hysterectomy is indicated for intractable postpartum
      hemorrhage when conservative therapy has failed to control bleeding. (II-B) 2.
      Tubo-ovarian abscesses that are ruptured or do not respond to antibiotics may be
      treated with hysterectomy and bilateral salpingo-oophorectomy in selected cases.
      (I-C) 3. Hysterectomy may be required for cases of acute menorrhagia refractory
      to medical or conservative surgical treatment. (II-C) Other Indications 1.
      Consultation with an oncologist or geneticist is recommended when considering
      hysterectomy and prophylactic oophorectomy for a familial history of ovarian
      cancer. (III-C) Surgical Approach 1. The vaginal route shoe should be considered
      as a first choice for all benign indications. The laparoscopic approach should be
      considered when it reduces the need for a laparotomy. (III-B) VALIDATION: Medline
      searches were performed in preparing this guideline with input from experts in
      their field across Canada. The guideline was reviewed and accepted by SOGC
      Council and Executive. SPONSOR: The Society of Obstetricians and Gynaecologists
      of Canada.

PMID- 12196889
TI  - The changing face of Canadian dermatology.
AB  - BACKGROUND: In 1986, Cosmair Canada, agent of the L'Oreal Group, sponsored a
      survey among Canadian dermatologists to measure the perceptions, attitudes,
      expectations, and needs of dermatologists regarding cosmetology. Fifteen years
      later, a new survey among Canadian dermatologists, again sponsored by L'Oreal,
      tries to capture the evolution and new trends. OBJECTIVES: This survey tries to
      capture the perceptions, attitudes, and expectations of Canadian dermatologists
      regarding cosmetology. METHODS: A questionnaire was sent to 394 members of the
      Canadian Dermatology Association; 99 responded (25%). The questionnaire, had 21
      questions regarding cosmetology, future trends in Canadian dermatology, and how
      dermatologists acquire the information required for their practice. RESULTS: More
      than ever, dermatologists are asked to deal with maintaining healthy, youthful
      skin. Cosmetology is a greater part of everyday practice. Laser and cosmetic
      dermatology will become more important in the future. CONCLUSIONS: Dermatologists
      are asked to provide information on the maintenance of healthy, young-looking
      skin and feel they need more information relating to cosmetology

PMID- 12196888
TI  - SOGC clinical practice guidelines. Hirsutism: evaluation and treatment.
AB  - OBJECTIVES: To review the etiology, evaluation, and treatment of hirsutism.
      EVALUATION: A thorough history and physical examination plus selected laboratory
      evaluations will confirm the diagnosis and direct treatment. TREATMENT:
      Pharmacologic interventions can suppress ovarian or adrenal androgen production
      and block androgen receptors in the hair follicle. Hair removal methods and
      lifestyle modifications may improve or hasten the therapeutic response. OUTCOMES:
      At least six to nine months of therapy are required to produce improvement in
      hirsutism. EVIDENCE: The quality of evidence reported in this guideline has been
      determined using the criteria described by the Canadian Task Force on the
      Periodic Health Examination. RECOMMENDATIONS: Hirsutism can be slowly but
      dramatically improved with a three-pronged approach to treatment: mechanical hair
      removal, suppression of androgen production, and androgen receptor blockade.
      Lifestyle changes including weight loss and exercise will lower serum androgen
      levels and improve self-esteem. The patient should be educated regarding
      associated health problems or long-term medical consequences of hyperandrogenism,
      including obesity, irregular menses, anovulation, infertility, pregnancy-induced
      hypertension, diabetes, hyperlipidemia, hypertension, and heart disease.

PMID- 12196890
TI  - Paraneoplastic pemphigus: a refractory autoimmune mucocutaneous disease.
AB  - BACKGROUND AND OBJECTIVE: We report on a 42-year-old man with Stage IIA non
      Hodgkin's lymphoma who developed a severe mucocutaneous blistering eruption. His
      diagnosis, paraneoplastic pemphigus, was based on clinical, histological, and
      immunofluorescence findings and confirmed by immunoprecipitation. Despite maximal
      therapy with plasmapheresis, corticosteroids, and mycophenolate mofetil and the
      subsequent addition of cyclophosphamide and cyclosporine, the condition was
      fatal. CONCLUSION: This case illustrates the refractory nature of this disease
      and the inadequacy of existing therapies.

PMID- 12196891
TI  - Nonpsoriatic uses of calcipotriol.
AB  - BACKGROUND: Calcipotriol is a synthetic vitamin D3 analog that binds to vitamin D
      receptors in epidermal cells. In vitro studies have shown that calcipotriol
      stimulates terminal cell differentiation and has antiproliferative effects. In
      vivo, calcipotriol has been shown to reduce the number of cycling epidermal
      cells. Calcipotriol also has less effect on calcium metabolism than calcitriol,
      which is the natural, bioactive, 1,25-dihydroxyvitamin D3. OBJECTIVE: These
      properties make calcipotriol an ideal candidate for the topical treatment of
      hyperproliferative skin disorders. While it has been approved for topical use in
      psoriasis, its potential for use in other dermatological disorders has not yet
      been fully investigated. CONCLUSION: This survey of the literature suggests that
      calcipotriol may show promise in the treatment of other conditions involving
      abnormal keratinization and hyperproliferation of epidermal cells. While some of
      these disorders are rare, and therefore difficult to study, further study into
      the nonpsoriatic uses of calcipotriol may be rewarding.

PMID- 12196892
TI  - A 10-year prospective study of patients with skin cancer.
AB  - BACKGROUND AND OBJECTIVE: To determine the incidence of new skin cancer formation
      in people who have had a nonmelanoma skin cancer (NMSC) removed. METHODS: A
      prospective study of Australian outpatients with histologically confirmed
      nonmelanoma skin cancer (NMSC). RESULTS: Four hundred eighty-one patients were
      entered in the study and 300 were followed for at least 10 years. Another skin
      cancer developed in 67.8% and multiple skin cancers (three or more) in 51.8%. A
      logistical regression analysis found that the main risk factors for new skin
      cancer formation were male sex and if the patient had multiple skin cancers. A
      squamous cell carcinoma (SCC) developed in 36% during the study and a melanoma in
      4.7% of men and 2.1% of women. Men who had a NMSC were 8 times more likely than
      the general population to develop a melanoma while women with NMSC were 4 times
      more likely. Three patients died of metastatic SCC and one of metastatic melanoma
      during the followup period. A multivariate analysis showed that multiple skin
      cancer formation was the main risk factor for SCC or melanoma formation.
      CONCLUSION: Patients with NMSC require careful followup as they have an increased
      risk of new cancer formation. Those with multiple skin cancer merit particularly
      careful followup as all develop another NMSC within 10 years and have a
      significantly increased risk of developing SCC or melanoma.

PMID- 12196893
TI  - HLA haplotypes and class II molecular alleles in Argentinian patients with
      pemphigus vulgaris.
AB  - BACKGROUND: Pemphigus is a group of chronic blistering autoimmune diseases of
      which pemphigus vulgaris (PV) is the more frequent clinical form. The association
      of PV with the HLA serotypes suggests that there is a genetic predisposition to
      the disease. OBJECTIVES: To determine the frequency of class I and class II HLA
      antigens and the allelic variants of the class II HLA antigens, DR and DQ, in
      patients with PV and to determine the relative risk. METHODS: An observational,
      prospective, transverse, and controlled study carried out between 1995 and 1999.
      Forty-seven patients with a diagnosis of PV and a control sampling of 199
      unselected individuals from the same ethnic group were included. The HLA alleles
      were determined by polymerase chain reaction. RESULTS: No significant
      associations were detected between HLA A, B, or C and our patients. The DR and DQ
      molecular alleles positively associated with PV were two different haplotypes:
      DRb1* 0402/DQb1* 0302 and DRb1* 1401/DQb1* 0503. CONCLUSIONS: In patients with
      the haplotype DRb1* 0402/DQb1* 0302 the affectation of 10%-30% of the corporal
      surface prevailed (ACS). In patients with DRb1* 1401/DRQb1* 0503, involvement of
      <10% of the ACS prevailed.

PMID- 12196894
TI  - von Willebrand Factor expression in a Shiga toxin-mediated primate model of
      hemolytic uremic syndrome.
AB  - von Willebrand Factor (vWF) is stored and released from activated or damaged
      endothelial cells and platelets, and its multimers have considerable
      prothrombotic properties. To investigate the role of vWF in the pathogenesis of
      post-diarrheal (D+) hemolytic uremic syndrome (HUS), we used a baboon model to
      study vWF expression following the intravenous administration of 100 ng/kg of
      Shiga toxin 1 (Stx 1), given either as a single dose, or as four divided doses,
      with and without lipopolysaccharide (LPS). vWF antigen was measured in plasma and
      urine obtained at 0, 12, 24, 36, 48, and 60 h by enzyme-linked immunosorbent
      assay (ELISA), and immunohistochemical expression of vWF in renal tissue obtained
      at autopsy was quantified by image analysis. Animals that received the single
      dose of Stx 1, or the four divided doses of Stx 1 plus LPS uniformly developed
      HUS, but those that received divided doses of Stx 1 without LPS, or LPS alone did
      not. Plasma vWF levels rose significantly in animals that received LPS, with or
      without Stx 1; but not in those that received Stx 1 alone. Urine vWF levels were
      generally undetectable. vWF expression was greater in renal tissue of animals
      that developed HUS than in those that did not, and was seen in both glomeruli,
      and, especially, peritubular capillaries. Since HUS developed in animals that did
      not experience a rise in plasma vWF levels, it does not appear that LPS-mediated
      systemic vWF release is essential to the pathogenesis of HUS in our model. The
      renal tissue findings, however, suggest a role for Stx-mediated intrarenal vWF
      release in the acute nephropathy of D+ HUS.

PMID- 12196895
TI  - Laparoscopic excision of a Brunner's gland hamartoma of the duodenum.
AB  - Brunner's gland hamartoma (adenoma) was first described in 1876. It is a rare
      hamartomatous lesion, with only 100 cases reported in the world literature.
      Treatment has been by endoscopic snaring. Open surgical excision was reserved for
      cases where snaring had failed. We report a case of a Brunner's gland hamartoma
      (2.4 cm) that was successfully resected by laparoscopic techniques. Postoperative
      hospital stay was brief (2 days), and there were no complications. This is the
      second reported case to be resected laparoscopically.

PMID- 12196896
TI  - Advanced bladder cancer...where are we now and where are we going?

PMID- 12196897
TI  - Chemotherapy in the post-MVAC era: the case for adjuvant chemotherapy.
AB  - Radical cystectomy for muscle invasive and locally advanced bladder cancer is the
      standard treatment modality in most of the Western industrialised countries.
      Rates of perioperative mortality from radical cystectomy have decreased to less
      than 2% over the past two decades due to advances in surgical technique and
      perioperative care. However, at least 40% of patients with pT3 bladder cancer and
      70% of patients with lymph node-positive disease develop tumour recurrence after
      radical treatment within the first 5 years when treated with radical cystectomy
      alone. After the efficacy of combination chemotherapy for metastatic urothelial
      cancer using methotrexate, vinblastine, adriamycin and cisplatin (MVAC) was first
      described in 1985, several cisplatin-based systemic regimens have been
      investigated as adjunctive treatment before or after therapy for locally advanced
      bladder cancer by radical surgery or radiation therapy. Three randomised studies
      have reported superior results of postoperative adjuvant systemic chemotherapy
      compared to radical cystectomy alone for locally advanced bladder cancer. All
      three studies demonstrated a significant survival benefit for bladder cancer
      patients receiving adjuvant combination therapy. Studies have been criticised for
      small patient numbers and statistical shortcomings. New effective antineoplastic
      agents, such as paclitaxel and gemcitabine, have evolved during the past decade
      as promising substances for the treatment of urothelial cancer. This article
      reviews adjuvant studies from the era of MVAC combination chemotherapy, as well
      as contemporary studies that discuss new antineoplastic agents for systemic
      adjuvant chemotherapy of locally advanced bladder cancer.

PMID- 12196898
TI  - Contemporary cystectomy and urinary diversion.
AB  - Radical cystectomy has emerged as the standard therapy for patients with invasive
      bladder cancer. Controversy is related to the indication, i.e. a low or high
      threshold. Meticulous pelvic lymphadenectomy can cure 20%-30% of patients with
      lymph node metastases, particularly those with limited node involvement.
      Unilateral nerve-sparing surgery is feasible in most patients without
      compromising oncological outcome and, besides erectile function, has an impact on
      the continence status after orthotopic bladder substitution. The excellent local
      control rates following radical cystectomy indicate that the weight of the
      problem in the future lies in reducing distant metastases. Orthotopic bladder
      substitution with a low-pressure ileal reservoir is currently the preferred
      method to reconstruct the lower urinary tract for both sexes following
      cystectomy. Long-term experience with follow-ups exceeding 10 years demonstrates
      a sustained favourable voiding outcome with slightly increasing incontinence
      rates as patients age.

PMID- 12196899
TI  - New drugs and new approaches for the treatment of metastatic urothelial cancer.
AB  - The median survival of patients with metastatic bladder cancer treated with M-VAC
      is approximately 1 year and long-term survival occurs in a small proportion of
      patients. Recent efforts to improve the outcome of patients with metastatic
      transitional cell carcinoma have focused on identifying new drugs with single
      agent activity and on their incorporation into platinum-based combination
      regimens. Paclitaxel, docetaxel, ifosfamide and gemcitabine are among the most
      active new agents. A large number of phase I-II trials have evaluated these
      agents in two- and three-drug combination regimens. The response proportion
      observed with these combinations varies considerably and median survival times
      range from 8 to 20 months. A better understanding of the molecular biology of
      bladder cancer will undoubtedly influence the selection of new therapeutic
      modalities. Molecular targeted small molecule therapy and monoclonal antibodies
      have begun to dominate contemporary studies. Whether or not this approach to
      therapy will lead to better results must still be determined.

PMID- 12196900
TI  - The role of chemotherapy and radiation in organ-preservation strategies for
      muscle-invasive bladder cancer.
AB  - Radical cystectomy with pelvic lymph node dissection has been accepted as the
      standard treatment for muscle-invasive bladder cancer. Radiation therapy and
      chemotherapy are increasingly being implemented in bladder-preservation protocols
      to provide an alternative treatment to cystectomy. We review experience with
      radiation and chemotherapy in treating bladder cancer and their use in bladder
      preservation protocols. Multimodality organ-sparing treatment strategies offer
      overall survival rates comparable to radical cystectomy and pelvic lymph node
      dissection in selected cases. However, bladder-preservation techniques risk local
      recurrence of potentially aggressive tumors whose long-term effect on cancer
      specific survival has not been fully characterized. No improvement in quality of
      life has clearly been demonstrated with bladder-preservation regimens. Bladder
      preservation protocols are costly and require precise coordination of multiple
      specialists as well as strict, life-long patient compliance. Bladder-preservation
      protocols should only be performed at tertiary care centers with experience in
      their administration and be limited to patients desiring an alternative
      cystectomy or who are not surgical candidates.

PMID- 12196901
TI  - Management of locally advanced bladder cancer: early vs deferred chemotherapy.
AB  - Locally advanced bladder cancer is associated with a high risk of local
      recurrence and distant metastases. Clinical and pathologic variables have been
      useful in predicting outcome in patients with muscle-invasive bladder cancer.
      Recently, a number of molecular prognostic markers have been identified that help
      predict tumor aggressiveness, response to chemotherapy, and survival.
      Transitional cell carcinoma is a chemosensitive tumor. The early use of
      chemotherapy to reduce the risk of recurrence and improve survival has been the
      focus of many randomized clinical trials. Unfortunately, the majority of studies
      have failed to show a survival advantage for chemotherapy-treated patients. Well
      designed prospective trials that target high-risk patients, defined by clinical,
      pathological, and molecular features, and incorporate new more tolerable
      chemotherapeutic agents are needed to clarify the benefit of early chemotherapy.

PMID- 12196902
TI  - Surgical bladder preserving strategies in the treatment of muscle-invasive
      bladder cancer.
AB  - Single modality bladder-sparing therapy for muscle-invasive bladder cancer,
      including transurethral resection (TUR), partial cystectomy, systemic
      chemotherapy or radiotherapy, have been demonstrated to result in insufficient
      local control of the primary tumour, as well as decreased long-term survival in
      the patients when compared to radical cystectomy. Therefore, multimodality
      treatment protocols that aim at bladder preservation and involve all of the
      aforementioned approaches have been established. Arguments for combining systemic
      chemotherapy with radiation are to sensitise tumour tissue to radiotherapy and to
      eradicate occult metastases that have already developed in as many as 50% of
      patients at the time of first diagnosis. It has been shown that the clinical
      outcome observed with this approach approximates that after radical cystectomy.
      Additionally, a substantial number of patients survive with an intact bladder.
      However, bladder-sparing approaches are costly, and require close co-operation
      between different clinical specialists as well as careful follow-up. The good
      long-term results that are observed after cystectomy and the creation of an
      orthotopic neobladder make the substantial advantage of a bladder preservation
      strategy questionable when the patient's quality of life is addressed.
      Additionally, bladder-sparing therapy-related side effects might result in an
      increased morbidity and mortality in those patients who need to undergo surgery
      due to recurrent or progressive disease. Multimodality bladder-sparing treatment
      is a therapeutic option that can be offered to the patient at centres that have a
      dedicated multidisciplinary team at their disposal. However, radical cystectomy
      remains the standard of care for muscle-invasive bladder cancer.

PMID- 12196903
TI  - Prognostic markers in muscle invasive bladder cancer.
AB  - Current tumor, node, and metastasis (TNM) staging and grading systems are
      insufficient to accurately predict the evolution of most invasive bladder cancers
      irrespective of treatment. Predicting which invasive tumors will or will not
      recur or metastasize early is crucial in order to dictate initial therapy and to
      better counsel the patient. A need for tumor markers that could be incorporated
      into clinical practice to add prognostic information to the conventional TNM and
      grading systems in terms of treatment response and prognosis is crucial. This
      review provides an update on the most promising reported single markers and
      pathways, including the cell cycle markers p53, p21 and p27, and potential
      targets for novel therapies, such as cyclooxygenase 2 (COX 2) and factors of
      angiogenesis. The critical steps remain the availability of large and well
      characterized data sets to validate the combination of markers, as well as high
      throughput methods to study tumor molecular fingerprints, such as DNA
      microarrays.

PMID- 12196904
TI  - Effects of thermal injury on skeletal metabolism in two strains of mice.
AB  - Long-term growth retardation occurs in children and osteopenias occur among
      children and adults who have been burned or suffer other injuries that result in
      a systemic inflammatory response. The purpose of this study was to define some of
      the growth, and to determine cancellous and cortical bone changes that occur
      following thermal injury in several contrasting strains of mice. Male C3H/HeN and
      Balb/c mice were given about a 20% total body thermal injury and 10 days later
      skeletal tissues were collected. The bone ash weights of the burned animals from
      both strains were less than their sham controls. In both strains, cancellous bone
      volumes were less in the burned animals than in their respective sham or baseline
      control groups. The loss of bone was particularly evident in the secondary
      spongiosa regions and also included a decrease in trabecular thickness and
      connectivity and an increase in trabecular separation. Longitudinal
      (endochondral) growth was suppressed in the burn animals. In the burned animals,
      indices of cancellous bone formation were substantially reduced whereas those in
      cortical bone were essentially nonexistent. The numbers of osteoclasts were
      increased in cancellous bone, and endocortical eroded surface was increased in
      the burn animals. These data show that there are rapid and profound changes in
      skeletal growth and metabolism in an experimental model of thermal injury. In
      general, a greater relative response was observed in the Balb/c vs. the C3H/HeN
      strain. Thermal injury resulted in a rapid and dramatic suppression of bone
      formation and endochondral growth with increased bone resorption in both
      cancellous and cortical bone.

PMID- 12196905
TI  - Vitamin D deficiency in guinea pigs: exacerbation of bone phenotype during
      pregnancy and disturbed fetal mineralization, with recovery by 1,25(OH)2D3
      infusion or dietary calcium-phosphate supplementation.
AB  - Vitamin D (D) deficiency during human pregnancy appears to disturb fetal growth
      and mineralization, but fetal development is normal in D-deficient rats and
      vitamin D receptor gene-ablated mice. We used the guinea pig model to investigate
      maternal and fetal effects of D deficiency. Pregnant (Pr) and nonpregnant (NPr)
      animals were fed a D-replete (+D) or D-deficient diet (-D) for 8 weeks. We
      further studied whether the effects of a -D diet are reversed by continuous
      1,25(OH)2D3 infusion (-D+1,25) and/or by a lactose-, Ca- and P-enriched D
      deficient diet (-D+Ca/P). Bone analyses included histomorphometry of the proximal
      tibiae, dual-energy X-ray absorptiometry (DXA), and quantitative computed
      tomography (QCT) of the femora. Depletion of 25(OH)D3 and 1,25(OH)2D3 levels and
      the D-deficiency syndrome were more severe in pregnant animals. Indeed, Pr/-D but
      not NPr/-D guinea pigs were hypophosphatemic, and showed robust increases in
      growth plate width and osteoid surface and thickness; in addition, bone mineral
      density on DXA was lower in Pr/-D animals only, which was exclusively in cortical
      bone on QCT. Bone phenotype was partly normalized in Pr/-D+1,25 and Pr/-D+Ca/P
      animals. Compared with +D fetuses, -D fetuses had very low or undetectable
      25(OH)D3 and 1,25(OH)2D3, were hypercalcemic and hypophosphatemic, and had lower
      osteocalcin levels. In addition, body weight and total body bone mineral content
      were 10-15% lower; histomorphometry showed hypertrophic chondrocyte zone
      expansion and hyperosteoidosis. 1,25(OH)2D3 levels were restored in -D+1,25
      fetuses, and the phenotype was partially corrected. Similarly, the fetal +D
      phenotype was rescued in large part in -D+Ca/P fetuses, despite undetectable
      circulating 25(OH)D3 and 1,25(OH)2D3. We conclude that pregnancy markedly
      exacerbates D deficiency, and that augmenting Ca and P intake overrides the
      deleterious effects of D deficiency on fetal development.

PMID- 12196906
TI  - Complexity and pharmacogenomics.

PMID- 12196908
TI  - Mapping zip codes in human vasculature.

PMID- 12196909
TI  - Bioinformatics in a post-genomics world--the need for an inclusive approach.

PMID- 12196910
TI  - Clinical significance of prognostic and predictive markers in colorectal cancer.

PMID- 12196911
TI  - Monoamine transporter gene structure and polymorphisms in relation to psychiatric
      and other complex disorders.
AB  - The norepinephrine, dopamine and serotonin transporters (NET, DAT and SERT,
      respectively), limit cellular signaling by recapturing released neurotransmitter,
      and serve as targets for antidepressants and drugs of abuse, emphasizing the
      integral role these molecules play in neurotransmission and pathology. This has
      compelled researchers to search for polymorphisms in monoamine (MA) transporter
      genes. Studies support linkage and association of MA transporter genetic
      variation in psychiatric and other complex disorders. Understanding the
      contribution of MA transporter polymorphisms to human behavior, disease
      susceptibility and response to pharmacotherapies will involve further progress in
      linkage and association that will be aided by both definition of highly selective
      phenotypes and utilization of a large number of polymorphic markers. The
      relationship of polymorphisms to alterations in transport capacity, likely a
      complex interaction, involving genetic background, disease state, and medication,
      will elucidate the means by which MA transporter genetic variability contributes
      to our individuality.

PMID- 12196912
TI  - Efficient discovery of single-nucleotide polymorphisms in coding regions of human
      genes.
AB  - Single nucleotide polymorphisms in protein coding regions (cSNPs) are of great
      interest for their effects on phenotype and potential for mapping disease genes.
      We have identified 5,400 novel exonic SNPs from alignments of public EST data to
      the draft human genome sequence, and approximately 12,000 more novel exonic SNPs
      from EST cluster alignments. We found 82% of the genomic-aligned SNPs and 63% of
      the EST-only SNPs to be detectably polymorphic in 20 Finnish DNA samples. 37% of
      the SNPs mapped to known protein coding regions, yielding 6,500 distinct, novel
      cSNPs from the two datasets. These data reveal selection against mutations that
      alter protein structure, and distinct classes of genes under strongly positive
      vs. negative pressure from natural selection for amino acid replacement (detected
      by K(A)/K(S)ratio). We have searched these cSNPs for compatibility with the amino
      acid profile at each site and structural impact on protein core stability.

PMID- 12196913
TI  - Differential metabolism of alprazolam by liver and brain cytochrome (P4503A) to
      pharmacologically active metabolite.
AB  - Cytochrome P450 (P450) is a superfamily of enzymes which mediates metabolism of
      xenobiotics including drugs. Alprazolam, an anti-anxiety agent, is metabolized in
      rat and human liver by P4503A1 and P4503A4 respectively, to 4-hydroxy alprazolam
      (4-OHALP, pharmacologically less active) and alpha-hydroxy alprazolam (alpha
      OHALP, pharmacologically more active). We examined P450 mediated metabolism of
      alprazolam by rat and human brain microsomes and observed that the relative
      amount of alpha-OHALP formed in brain was higher than liver. This
      biotransformation was mediated by a P450 isoform belonging to P4503A subfamily,
      which is constitutively expressed in neuronal cells in rat and human brain. The
      formation of larger amounts of alpha-OHALP in neurons points to local modulation
      of pharmacological activity in brain, at the site of action of the anti-anxiety
      drug. Since hydroxy metabolites of alprazolam are hydrophilic and not easily
      cleared through blood-CSF barrier, alpha-OHALP would potentially have a longer
      half-life in brain.

PMID- 12196914
TI  - Pharmacogenomic analysis: correlating molecular substructure classes with
      microarray gene expression data.
AB  - Genomic studies are producing large databases of molecular information on cancers
      and other cell and tissue types. Hence, we have the opportunity to link these
      accumulating data to the drug discovery processes. Our previous efforts at
      'information-intensive' molecular pharmacology have focused on the relationship
      between patterns of gene expression and patterns of drug activity. In the present
      study, we take the process a step further-relating gene expression patterns, not
      just to the drugs as entities, but to approximately 27,000 substructures and
      other chemical features within the drugs. This coupling of genomic information
      with structure-based data mining can be used to identify classes of compounds for
      which detailed experimental structure-activity studies may be fruitful. Using a
      systematic substructure analysis coupled with statistical correlations of
      compound activity with differential gene expression, we have identified two
      subclasses of quinones whose patterns of activity in the National Cancer
      Institute's 60-cell line screening panel (NCI-60) correlate strongly with the
      expression patterns of particular genes: (i) The growth inhibitory patterns of an
      electron-withdrawing subclass of benzodithiophenedione-containing compounds over
      the NCI-60 are highly correlated with the expression patterns of Rab7 and other
      melanoma-specific genes; (ii) the inhibitory patterns of indolonaphthoquinone
      containing compounds are highly correlated with the expression patterns of the
      hematopoietic lineage-specific gene HS1 and other leukemia genes. As illustrated
      by these proof-of-principle examples, we introduce here a set of conceptual tools
      and fluent computational methods for projecting directly from gene expression
      patterns to drug substructures and vice versa. The analysis is presented in terms
      of the NCI-60 cell lines and microarray-based gene expression patterns, but the
      concept and methods are broadly applicable to other large-scale pharmacogenomic
      database sets as well. The approach (SAT for Structure-Activity-Target) provides
      a systematic way to mine databases for the design of further structure-activity
      studies, particularly to aid in target and lead identification.

PMID- 12196917
TI  - Immunohistochemical markers of cell immortality.

PMID- 12196916
TI  - Functional analysis of RUNX2 mutations in Japanese patients with cleidocranial
      dysplasia demonstrates novel genotype-phenotype correlations.
AB  - Cleidocranial dysplasia (CCD) is an autosomal dominant heritable skeletal disease
      caused by heterozygous mutations in the osteoblast-specific transcription factor
      RUNX2. We have performed mutational analysis of RUNX2 on 24 unrelated patients
      with CCD. In 17 patients, 16 distinct mutations were detected in the coding
      region of RUNX2: 4 frameshift, 3 nonsense, 6 missense, and 2 splicing mutations,
      in addition to 1 polymorphism. The missense mutations were all clustered within
      the Runt domain, and their protein products were severely impaired in DNA binding
      and transactivation. In contrast, two RUNX2 mutants had the Runt domain intact
      and remained partially competent for transactivation. One criterion of CCD, short
      stature, was much milder in the patients with the intact Runt domain than in
      those without. Furthermore, a significant correlation was found between short
      stature and the number of supernumerary teeth. On the one hand, these genotype
      phenotype correlations highlight a general, quantitative dependency, by skeleto
      dental developments, on the gene dosage of RUNX2, which has hitherto been
      obscured by extreme clinical diversities of CCD; this gene-dosage effect is
      presumed to manifest on small reductions in the total RUNX2 activity, by
      approximately one-fourth of the normal level at minimum. On the other hand, the
      classic CCD phenotype, hypoplastic clavicles or open fontanelles, was invariably
      observed in all patients, including those with normal height. Thus, the
      cleidocranial bone formation, as mediated by intramembranous ossification, may
      require a higher level of RUNX2 than does skeletogenesis (mediated by
      endochondral ossification), as well as odontogenesis (involving still different
      complex processes). Overall, these results suggest that CCD could result from
      much smaller losses in the RUNX2 function than has been envisioned on the basis
      of the conventional haploinsufficiency model.

PMID- 12196915
TI  - Neocentromeres: role in human disease, evolution, and centromere study.
AB  - The centromere is essential for the proper segregation and inheritance of genetic
      information. Neocentromeres are ectopic centromeres that originate occasionally
      from noncentromeric regions of chromosomes. Despite the complete absence of
      normal centromeric alpha-satellite DNA, human neocentromeres are able to form a
      primary constriction and assemble a functional kinetochore. Since the discovery
      and characterization of the first case of a human neocentromere in our laboratory
      a decade ago, 60 examples of constitutional human neocentromeres distributed
      widely across the genome have been described. Typically, these are located on
      marker chromosomes that have been detected in children with developmental delay
      or congenital abnormalities. Neocentromeres have also been detected in at least
      two types of human cancer and have been experimentally induced in Drosophila.
      Current evidence from human and fly studies indicates that neocentromere activity
      is acquired epigenetically rather than by any alteration to the DNA sequence.
      Since human neocentromere formation is generally detrimental to the individual,
      its biological value must lie beyond the individual level, such as in karyotype
      evolution and speciation.

PMID- 12196919
TI  - Immunohistochemical detection of telomerase reverse transcriptase in colorectal
      adenocarcinoma and benign colonic mucosa.
AB  - Telomerase activity (TA) is increased in human cancers and cell lines and is
      thought to contribute to their immortality. High TA has been found to correlate
      with aggressive tumor behavior. The aim of this study was to determine whether
      increased TA in colorectal carcinoma (CRC) correlates with survival. Formalin
      fixed and paraffin-embedded tissue sections from 82 CRC and 6 cases of benign
      colon with diverticulosis were immunohistochemically stained for telomerase
      reverse transcriptase (TRT) using the immunoperoxidase method. The percentage of
      positive nuclei was determined for each case. Survival analysis was performed
      using the Kaplan-Meier method. TRT immunoreactivity was always nuclear. In normal
      colonic mucosa, TRT immunoreactivity was detected in the bottom of crypts.
      However, in normal colon adjacent to CRC, telomerase immunoreactivity was
      detected throughout the length of the crypts, including the upper third, and
      frequently in the surface epithelium. Telomerase immunoreactivity in more than
      25% of the cancer cell nuclei was associated with significantly poorer patient
      survival (P = 0.0081). We conclude that increased TA in CRC, as demonstrated by
      TRT immunostaining, is associated with poorer survival, and that TA is present in
      normal colonic mucosa and is increased in colonic mucosa near CRC. Additional
      studies with larger patient samples and multivariate analysis are needed to
      determine whether TRT expression is an independent prognostic factor in CRC.

PMID- 12196918
TI  - Expression of apoptosis-related proteins in Barrett's metaplasia-dysplasia
      carcinoma sequence: a switch to a more resistant phenotype.
AB  - Barrett's esophagus, or columnar-lined esophagus (CLE), is a premalignant
      disorder in which the stratified squamous epithelium is replaced by metaplastic
      epithelium. To gain more insight into the process of carcinogenesis in CLE, we
      studied several factors involved in the apoptotic pathway in biopsies with
      gastric metaplasia (GM), intestinal metaplasia (IM), dysplasia, and/or
      adenocarcinoma. Immunohistochemistry was performed for Fas, Bcl-2, Bax, Bcl-xl,
      inducible nitric oxide synthase (iNOS), and cyclooxygenase 2 (COX-2). Fas
      staining was positive in the epithelium of all biopsies from patients with CLE
      but negative in normal gastric mucosa. Fas staining was positive in all tumor
      cells of the 8 cases containing adenocarcinoma. Bcl-2 was positive in lamina
      propria immune cells of all specimens. Bax staining was positive in the
      epithelium of all biopsies, including tumor cells. Bcl-xl was positive in
      dysplasia and tumor cells, but negative in 8 of 17 biopsies containing IM. iNOS
      was positive in 20 of 21 biopsies with IM and in 4 of 8 dysplasia biopsies. COX-2
      was positive in 7 of 8 adenocarcinomas. We conclude that the apoptotic balance in
      the transformation from IM to adenocarcinoma switches to an antiapoptotic
      phenotype because of increased Bcl-xl expression and decreased Bax expression.
      Fas can be used as a marker for the differentiation of gastric mucosa and
      metaplasia in the esophagus. iNOS is highly positive in CLE-associated intestinal
      metaplasia. COX-2 is negative in nonmalignant CLE. Therefore, pharmacologic
      inhibition of COX-2 activity is unlikely to be effective in the preventing CLE
      associated adenocarcinoma. There was no clear correlation between iNOS expression
      and activation of proapoptotic and antiapoptotic genes.

PMID- 12196920
TI  - Expression of human telomerase RNA component and telomerase reverse transcriptase
      mRNA in atypical adenomatous hyperplasia of the lung.
AB  - It has been suggested that atypical adenomatous hyperplasia (AAH) may be a
      precursor of peripheral adenocarcinoma of the lung. Telomerase is a
      ribonucleoprotein enzyme that synthesizes telomeric DNA onto chromosomal ends.
      Its activity is believed to be crucial for cellular immortality, and it is
      thought to participate in the development of most human cancers. However, little
      is known about the regulation of telomerase in AAH. We investigated the
      expression of human telomerase RNA component (hTERC) and telomerase reverse
      transcriptase (hTERT) mRNA using in situ hybridization in surgically resected
      formalin-fixed, paraffin-embedded specimens: 29 AAHs (with 11 lesions interpreted
      as low-grade AAH and 18 as high-grade AAH) and 40 peripherally located
      nonmucinous bronchioloalveolar carcinomas (NMBACs) measuring < or = 20 mm in
      greatest diameter. Positive expressions of hTERC and hTERT mRNA were recognized
      in 27.3% and 27.3% of low-grade AAHs, 72.2% and 77.8% of high-grade AAHs, and
      97.5% and 97.5% of NMBACs, respectively. Statistically, significant differences
      in both expressions could be shown between low-grade AAH and high-grade AAH and
      between high-grade AAH and NMBAC. Thus, in terms of the incidence of these
      expressions, high-grade AAH was intermediate between low-grade AAH and NMBAC and
      tended to be closer to NMBAC. These results suggest that high-grade AAH may be a
      precursor lesion of peripherally located NMBAC.

PMID- 12196921
TI  - Expression of mos in astrocytic tumors and its potential role in neoplastic
      progression.
AB  - The c-mos gene and its protein product mos, components of the mitogen-activated
      protein kinase transduction pathway, are known to be involved in the control of
      meiosis and mitosis. Apart from a study on lung carcinomas, there is little
      information about its role in human neoplasia. The aim of this study was to
      investigate expression of mos in astrocytic tumors and to correlate it with
      accumulation of p53. We studied expression of mos in 62 cases of supratentorial
      astrocytic tumor. Intracytoplasmic immunostaining for mos was found in 28 (45%)
      cases: 3 of 20 (15%) grade 2 astrocytomas, 9 of 20 (45%) grade 3 anaplastic
      astrocytomas, and 16 of 22 (73%) glioblastomas. Immunopositivity for mos
      correlated significantly (P < 0.01) with tumor grade but not with p53 expression.
      In contrast to the findings in relation to lung tumors, immunopositivity for mos
      in astrocytic tumors did not predict recurrence-free or overall survival time.
      Cytoplasmic immunostaining was observed in scattered large cortical neurons
      adjacent to tumors, possibly due to stress-induced abortive entry into the cell
      cycle. The correlation of mos immunopositivity with tumor grade may reflect the
      expansion of more malignant mos-positive clones. This study provides evidence
      that mos may be involved in the neoplastic progression of a proportion of
      astrocytic tumors.

PMID- 12196922
TI  - Prognostic significance of cyclooxygenase-2 pathway and angiogenesis in head and
      neck squamous cell carcinoma.
AB  - Prostaglandins play a critical role in tumor development and growth by regulating
      numerous biologic processes, including tumor angiogenesis, with clear prognostic
      and therapeutic implications. The aim of this study was to investigate the
      prognostic relevance of cyclooxygenase-2 (COX-2) pathway activation in head and
      neck squamous cell carcinoma (HNSCC). COX-2 activity was analyzed in 52
      consecutive patients by assessing protein expression and prostaglandin E(2)
      (PgE(2)) levels and was then correlated to vascular endothelial growth factor
      (VEGF) expression and tumor angiogenesis. We evaluated the prognostic impact of
      these parameters by Kaplan-Meier and Cox survival analysis. COX-2 expression by
      tumor cells was closely correlated to VEGF expression and to tumor
      vascularization. According to Kaplan-Meier analysis, patients with COX-2 tumor
      overexpression and with higher PgE(2) tumor levels had significantly shorter
      overall survival estimates (P = 0.022 and P = 0.033, respectively). Analogously,
      patients with more-vascularized tumors had worse survival than those with less
      vascularized cancers (P = 0.032). Cox multivariate analysis demonstrated that the
      most significant prognostic factors were presence of lymph node metastasis, tumor
      vascularization, COX-2 protein expression, and PgE(2) tumor levels. This study
      demonstrates a close correlation between COX-2 pathway, VEGF expression, and
      tumor angiogenesis in HNSCC. In addition, COX-2 overexpression and higher tumor
      vascularization appear to predict a shorter survival in patients with head and
      neck cancer.

PMID- 12196923
TI  - Molecular and genetic abnormalities in radial scar.
AB  - Hyperplasia of usual type (HUT) may be an early precursor of breast carcinoma and
      has been shown to contain molecular and genetic abnormalities previously seen in
      more advanced breast lesions, such as allelic imbalance (AI) and coexpression of
      estrogen receptor-alpha (ER) and the proliferation marker Ki67. We have examined
      hyperplastic and other areas from within radial scar (RS) for such abnormalities,
      to explore whether such regions of RS are similar at the molecular and genetic
      level to histologically similar lesions found independent of RS. Abnormal
      expression of ER and Ki67 in hyperplastic foci and other histologically distinct
      areas within RS was detected by dual-label immunofluorescence. Subtle differences
      in expression patterns were seen compared to similar lesions outside RS, with a
      lower overall level of ER overexpression in HUT within RS (P = 0.0012) and less
      evidence of the abnormal ER association with Ki67 (P = 0.004). AI of chromosome
      16q and 8p was detected in RS, indicating that at least some areas of RS are
      clonal and neoplastic, but no clear relationship to ER dysregulation was found.
      Different genetic losses seen in microdissected areas of the same RS indicated
      clonal differences between these areas. The role of RS as a marker of malignancy
      and relative risk of breast cancer remains uncertain. Nonetheless, here we
      provide evidence that some molecular and genetic changes that occur to a greater
      degree in breast cancer and some premalignant breast lesions are present in a
      minority of RS.

PMID- 12196924
TI  - Expression of RB2/p130 tumor-suppressor gene in AIDS-related non-Hodgkin's
      lymphomas: implications for disease pathogenesis.
AB  - In this study we examined 21 cases of AIDS-related lymphomas for genomic
      organization and expression of RB2/p130 oncosuppressor gene and compared the
      results with the proliferative features of these neoplasms. We found no mutations
      in the RB2/p130 gene and unusually high percentages of cells expressing nuclear
      pRb2/p130 in tumors with a high proliferative activity, such as AIDS-related
      lymphomas. These findings might suggest that a molecular mechanism usually
      observed in viral-linked oncogenesis could be involved. We performed in vitro and
      in vivo binding assays to investigate whether the human immunodeficiency virus
      (HIV) gene product Tat and Rb2/p130 could interact. The results of these assays
      revealed that the HIV-1 Tat protein binds specifically to pRb2/p130. This may
      result in the inactivation of its oncosuppressive properties and the induction of
      genes needed to proceed through the cell cycle including p107, cyclin A, and
      cyclin B. Using single-cell polymerase chain reaction (PCR) assay, we found HIV-1
      DNA in the neoplastic cells of only 2 of the 21 cases examined, whereas PCR on
      whole tissue revealed HIV-1 DNA in all of the cases. Furthermore, a diffuse and
      nuclear stain was observed in tissue sections with anti-Tat monoclonal antibody.
      These findings are in accordance with the notion that soluble Tat protein could
      function as a biologically active extracellular protein released by infected
      cells and taken up readily by uninfected B cells. In conclusion, our results seem
      to suggest that pRb2/p130 oncosuppressor protein may be a target in the
      interaction between the HIV-1 gene products and host proteins.

PMID- 12196926
TI  - Inverse relationship between matrilysin expression and proliferative activity of
      cells in advanced gastric carcinoma.
AB  - Matrilysin is known to play an important role in tumor invasion, but it is not
      known yet whether there is a direct relationship between matrilysin expression
      and cell proliferation. Therefore, we compared expression of matrilysin with
      expression of Ki-67, a marker of cell proliferation, at different tumor areas in
      130 advanced gastric carcinomas. Both matrilysin and Ki-67 were distributed
      heterogeneously in tumor tissue. Matrilysin frequently was expressed at the
      invasive front, whereas Ki-67-positive cells frequently were located both at the
      tumor surface and in central tumor cell nests. The patterns of gastric cancer
      cell invasion into the surrounding tissues are described as alpha-infiltration,
      beta-infiltration, and gamma-infiltration, respectively, according to the
      guidelines of the Japanese Research Society for Gastric Cancer Study. The mean
      matrilysin labeling index (LI) of gamma-infiltration tumors at the invasive front
      was significantly greater than that of alpha- and beta-infiltration tumors (P
      =.01). In contrast to the matrilysin LI, the mean Ki-67 LI of gamma-infiltration
      tumors was significantly lower than that of alpha- and beta-infiltration tumors
      (P =.02). Moreover, Ki-67 antigen was absent in matrilysin-positive tumor cells
      and vice versa. We concluded that matrilysin expression was related inversely
      with proliferative activity of tumor cells and that matrilysin expression could
      possibly serve as a useful marker of tumor invasion.

PMID- 12196925
TI  - Focal follicular features in tonsillar diffuse large B-cell lymphomas: follicular
      lymphoma with diffuse areas or follicular colonization.
AB  - Focal follicular features in diffuse large B-cell lymphomas (DLBCLs) are bound to
      raise the question of follicular lymphoma (FL) with diffuse areas, because the
      diagnosis of FL is based on the presence of follicular areas, even though focal.
      We report 7 cases of primary tonsillar DLBCLs with focal follicular features that
      presented with morphologic, immunohistochemical, and biological features distinct
      from those of FL. Histologically, these tumors were characterized by involvement
      of pericryptal follicles with adjacent dominant diffuse areas. Monomorphous large
      tumor cells were evenly spaced with abundant, often clear cytoplasm, and blastoid
      nuclei often with a delicate nuclear membrane. Importantly, residual germinal
      centers (GCs) were present in the form of either an intrafollicular GC remnant or
      an isolated GC in the midst of diffuse tumor. An extrafollicular and/or
      parafollicular growth pattern was also observed. Bcl-6 staining revealed a
      predominantly sporadic occurrence of Bcl-6(+) cells, comprising <50% of tumor
      cells, and none displayed diffusely dense collections (>75%) of Bcl-6(+) tumor
      cells characteristic of the GC or FL. Staining for CD10 was negative in 6 cases.
      Five of 7 patients were younger than 60, the median age of other patients with
      primary tonsillar DLBCL. No extratonsillar involvement was seen at 18 months
      after diagnosis. After chemotherapy or radiotherapy, complete remission was
      achieved with ease in all patients, but 2 patients who were treated with
      chemotherapy alone relapsed at 24 and 30 months. In conclusion, tonsillar DLBCL
      includes a small (10%) but distinct subgroup that warrants distinction from FL
      with predominant diffuse areas or de novo DLBCL. It appears that the focal
      follicular features in tonsillar DLBCL likely represent follicular colonization
      of marginal zone B-cell lymphoma, probably high-grade, if the possibility of FL
      is excluded.

PMID- 12196927
TI  - Overexpression of gamma-glutamylcysteine synthetase in human malignant
      mesothelioma.
AB  - Mesothelioma is a fatal tumor resistant to all treatment modalities for reasons
      that are still unresolved. Glutathione (GSH)-associated pathways are induced by
      oxidants and cytotoxic drugs, and they are also involved in the progression and
      resistance of some tumor cells in vitro. The rate-limiting enzyme in GSH
      biosynthesis is gamma-glutamylcysteine synthetase (gamma GCS). However, the
      expression of this enzyme has not been systematically investigated in malignant
      tumors, and there are no studies of gamma GCS in biopsy specimens of malignant
      mesothelioma. We investigated the immunohistochemical distribution and expression
      of both subunits of gamma GCS in healthy pleural mesothelium, pleural
      mesothelioma tumor biopsy samples (34 cases), and mesothelioma cells in culture
      (7 cell lines). Nonmalignant mesothelium showed no immunoreactivity for either
      subunit in any of the cases. The heavy (catalytic) subunit of gamma GCS was
      highly immunostained in 29 and weakly positive in 5 cases. High-moderate and weak
      immunoreactivity of the light (regulatory) subunit of gamma GCS was found in 15
      and 7 tumors, respectively, whereas 12 cases showed no reactivity. There was no
      correlation with either catalytic or regulatory subunit expression and patient
      survival. There was, however, a significant correlation between the heavy chain
      and multidrug resistance protein (MRP) 2 (P =.048), whereas no correlation was
      observed between the light chain and MRP1 or MRP2. Treatment of cultured
      mesothelioma cells with buthionine sulfoximine (BSO), to inhibit gamma GCS,
      significantly potentiated cisplatin-induced cytotoxicity mainly by nonapoptotic
      mechanism when assessed by counting the living cells, TUNEL (terminal
      deoxytransferase-mediated dUTP nick-end labeling) assay, and caspase-3 cleavage.
      In conclusion, gamma GCS is highly positive in most cases of malignant
      mesothelioma and may play an important role in the primary drug resistance of
      this tumor in vivo.

PMID- 12196928
TI  - Inadequate formalin fixation decreases reliability of p27 immunohistochemical
      staining: probing optimal fixation time using high-density tissue microarrays.
AB  - Immunohistochemical analysis of molecular targets in clinical tissues is
      increasingly becoming central to our ability to render diagnoses, to predict
      prognosis, to select patients for appropriate therapies, and to provide surrogate
      end points for therapeutic monitoring. For example, reduction of
      immunohistochemical staining for the cyclin-dependent kinase inhibitor p27(Kip1)
      has been proposed as a potential prognostic biomarker in prostate, breast, and
      gastrointestinal tumors. We observed that with our standard formalin fixation in
      rapidly processed (same-day) radical prostatectomy specimens, there is often a
      gradient of p27(Kip1) staining in normal prostate epithelium, with more staining
      near the periphery and less staining toward the center of the sample. This raised
      the hypothesis that the reliability of staining for p27(Kip1) is decreased in
      inadequately fixed tissues. The implications of this, if true, are that many
      studies using p27(Kip1) for prognostic purposes may be subject to unpredictable
      artifacts, and hence unreliable results, if the fixation of the specimens is not
      well controlled. The objectives of the present study were (1) to formally test
      the hypothesis that inadequate fixation time is responsible for apparent loss of
      p27(Kip1) nuclear staining and (2) to test a recently proposed method for
      improving the uniformity of immmunohistochemical staining using formalin
      injection. Prostate tissue sections from radical prostatectomy specimens were
      either processed immediately (zero time fixation) or fixed for 1, 2, 3, or 8 days
      in 10% neutral buffered formalin before processing into paraffin. To assure
      identical antigen retrieval and immunohistochemical staining conditions for
      specimens fixed for different lengths of time, 2 high-density tissue microarrays
      (TMAs), containing 564 tissue samples (0.6 mm in diameter) were constructed.
      Based on an estimate of the percentage of nuclei in normal prostatic epithelial
      secretory cells with strong staining, quality of p27(Kip1) staining was graded in
      a blinded fashion with respect to fixation time. There was a significant increase
      in the percentage of cores that were scored as "strong" as fixation time
      increased from 0 (same-day processing) to 1 or more days (P <.0001).
      Interestingly, even at 8 days of fixation, there was excellent staining that was
      superior to the same-day processing. Based on these results, we conclude the
      following: (1) for large clinical specimens that have been fixed briefly to
      decrease diagnostic turn-around time, the reliability of interpretation of
      immunohistochemical staining may be quite limited; (2) for p27(Kip1), decreased
      antigen staining as a result of the widely held concept of "overfixation" is much
      less of a problem than "underfixation"; (3) formalin injection produces a marked
      improvement in staining for several markers, including p27(Kip1); and (4) high
      density TMAs, which assure identical test conditions, provide an excellent
      platform on which to evaluate the effects of tissue fixation on
      immunohistochemical staining.

PMID- 12196929
TI  - Atypical epithelial proliferations in acquired renal cystic disease harbor
      cytogenetic aberrations.
AB  - Acquired renal cystic disease (ARCD) complicating end-stage renal failure confers
      an increased risk for renal cell carcinoma, and atypical epithelial proliferation
      in the cysts may represent the precursor lesion. In this report we used an
      interphase cytogenetic technique to analyze the karyotypic features of various
      forms of atypical epithelial proliferations in a patient with ARCD. Both kidneys
      harbored numerous simple and atypical cysts. In addition, papillary tufts and a
      hitherto undescribed cribriform epithelial proliferation were found in the right
      kidney. The left kidney contained a 10-mm renal cell carcinoma with features
      indeterminate between clear cell and papillary types. There was gain of
      chromosome 7 in the papillary tufts; gain of chromosomes 7 and 17 in the
      cribriform lesion; gain of chromosomes 7, 12, 17, 20, and Y in the atypical
      cysts; and gain of chromosomes 7, 12, 17, and 20 in the renal cell carcinoma.
      These chromosomal aberrations suggest that atypical epithelial proliferations in
      ARCD represent early neoplastic lesions.

PMID- 12196930
TI  - Adult-type hepatocellular carcinoma in the center of a fibrolamellar
      hepatocellular carcinoma.
AB  - A large hepatic tumor was detected in the noncirrhotic liver of a 27-year-old
      female patient. The tumor was radiologically characterized by a peripheral mass
      encircling a central ovoid tumor, and was resected by an extended right
      hemihepatectomy. Histologic examination revealed that the peripheral and major
      component of the tumor represented a fibrolamellar hepatocellular carcinoma,
      whereas the central, well-demarcated tumor was a less well-differentiated adult
      type hepatocellular carcinoma completely encircled by the former. Cells of the
      peripheral tumor mass abundantly expressed cytokeratin-7, typically present in
      the fibrolamellar variant, whereas no cytokeratin-7 immunoreactivity was found in
      the central tumor. To our knowledge, this is the first reported case of a not
      admixed but clearly separated evolution of these 2 histologic patterns within the
      same tumor, and suggests that the 2 types of hepatocellular carcinoma may share a
      common pathogenic pathway.

PMID- 12196931
TI  - T-cell blast crisis of chronic myelogenous leukemia manifesting as a large
      mediastinal tumor.
AB  - We report an unusual case of T-cell blast crisis of chronic myelogenous leukemia
      (CML) with a clinical presentation more typical of de novo T-cell lymphoblastic
      lymphoma. The patient was a 32-year-old man who presented with acute superior
      vena cava syndrome 19 months after an initial diagnosis of CML and 5 months after
      allogeneic bone marrow transplantation. The tumor was composed of primitive
      lymphoid cells expressing CD2, CD3, CD4, CD5, CD7, CD8, and CD10. Although the
      clinical features were more typical of acute lymphoblastic leukemia/lymphoma,
      fluorescence in situ hybridization analysis showed the bcr-abl fusion gene within
      blastic tumor cells. This finding confirmed that the mass represented a blastic
      transformation of CML. We use the unusual features of the current case and the
      previous reports to suggest that the development of T-cell blast crisis of CML is
      dependent on the presence of both marrow and extramedullary disease and a
      mechanism to evade apoptosis.

PMID- 12196932
TI  - Working in clients' homes: the impact on the mental health and well-being of
      visiting home care workers.
AB  - The purpose of this paper is to examine the effects of working in clients' homes
      on the mental health and well-being of visiting home care workers. This paper
      reports the results of a survey of 674 visiting staff from three non-profit home
      care agencies in a medium-sized city in Ontario, Canada. Survey results are also
      complimented by data from 9 focus groups with 50 employees. For purposes of this
      study, home care workers include visiting therapists, nurses, and home support
      workers. Mental health and well-being is measured by three dependent variables:
      stress; job stress; and intrinsic job satisfaction. Multiple least squared
      regression analyses show several structural, emotional, physical, and
      organizational working conditions associated with the health and well-being of
      visiting home care workers. Overall, results show that workload, difficult
      clients, clients who take advantage of workers, sexual harassment, safety
      hazards, a repetitious job, and work-related injuries are associated with poorer
      health. Being fairly paid, having good benefits, emotional labour, organizational
      support, control over work, and peer support are associated with better health.
      Results suggest that policy change is needed to encourage healthier work
      environments for employees who work in clients' homes.

PMID- 12196933
TI  - Development of a tool for assessment and care planning for dementia-related
      problem behaviors in home and community-based services programs: the Problem
      Behavior Inventory.
AB  - OBJECTIVE: To describe development, validity, and application of the Problem
      Behavior Inventory (PBI), a tool to assess dementia-related problem behaviors
      (DRPBs) in community-based populations. DATA SOURCES AND STUDY SETTING:
      Demographic, contact, and disease-specific data were extracted from client files
      from a Medicaid-funded home and community-based services program. Primary
      caregivers completed standard surveys relating to the care recipients' memory,
      mood, and behaviors. The client (care recipient) completed the Mini-Mental Status
      Exam (MMSE). STUDY DESIGN: Cognitively impaired clients, enrolled in the
      Community Care Services Program (CCSP) during a reference month, and their
      primary caregivers, were identified by CCSP case managers for participation in
      the study. Primary caregivers completed the Revised Memory and Behavior Problem
      Checklist (RMBPC). Clients screening positive for the presence of DRPBs based on
      caregiver responses to the RMBPC were then assessed using the Problem Behavior
      Inventory (PBI). PRINCIPLE FINDINGS: Within the CCSP sample, the most prevalent
      behavior was appearing sad or depressed (67%), while the most frequent behavior
      was seeking attention, occurring at least daily in 58% of the group. The most
      bothersome behaviors were being sexually inappropriate, wandering, and
      misbehaving in public. Examination by behavior category (physical, verbal, mood,
      etc.) revealed a strong relationship between level of bother and behavior
      frequency. Frequency of verbal behaviors was positively related to MMSE scores,
      whereas frequency of ADL-related behaviors was inversely related to MMSE scores.
      Bother scores were not associated with MMSE scores. CONCLUSIONS: This study
      documents that the PBI is a valid, useful, and feasible tool for assessing DRPBs
      in community populations. Case managers using the PBI can determine specific
      problem behavior areas among client populations and for individual clients and
      institute client-specific interventions to address each issue.

PMID- 12196934
TI  - Home health and home care in Massachusetts after the Balanced Budget Act of 1997:
      implications of cost containment pressures for service authorizations.
AB  - This paper explores the response of the Massachusetts state-funded home care
      program for the elderly when its clients encountered barriers to the receipt of
      home health services because of HMO enrollment and the implementation of the
      Balanced Budget Act of 1997. Clients of three regional case management agencies
      serving the Massachusetts state home care program whose home care services were
      interrupted because of hospitalization between January 1 and April 30, 1999 and
      whose services were resumed after they returned home were studied. Detailed data
      are reported that show how the long-term personal assistance services provided
      through the state program were often complemented by temporary home health
      services after elders returned home. The multivariate analysis revealed that the
      authorization of state-funded personal care services was keyed to the status of
      home health aide services. After hospitalization, the presence of a home health
      aide reduced the likelihood of authorization of personal care. At final
      assessment, the situation was reversed, that is, the withdrawal of a home health
      aide increased the likelihood of authorization of personal care. The findings
      suggest that more restrictive Medicare reimbursement policies for home health
      services led to greater state expenditures for personal care services. In other
      words, less generous Medicare financing shifted a greater portion of the burden
      of financing home care to the state of Massachusetts. These findings raise
      important policy questions about the balance of responsibility between the
      federal government and states to provide financing of home care services for the
      elderly.

PMID- 12196935
TI  - Chinese Dementia Specialist Education Program: training Chinese American health
      care professionals as dementia experts.
AB  - A Chinese Dementia Specialist Education Program (CDSEP) was launched in the
      Greater Boston Area to educate Chinese American health care providers who lacked
      adequate dementia education and services. This program trained bilingual health
      care providers to identify, assess and serve people with dementia and their
      families, and raised dementia awareness in Chinese American communities. The ten
      month follow-up survey documented that the sixteen graduates helped over 70
      families and held 76 workshops and formal and informal discussions, reaching over
      400 people. The CDSEP demonstrates that a "Train the Trainer" model is an
      effective approach for building dementia care capacity in community-based
      agencies, increasing outreach to people with dementia and their families, and for
      raising dementia awareness in bilingual and minority communities.

PMID- 12196936
TI  - BNAs: novel nucleic acid analogs with a bridged sugar moiety.
AB  - This article deals with our recent studies on the synthesis of BNAs (Bridged
      Nucleic Acids), novel nucleic acid analogs bearing a preorganized sugar
      conformation by a bridged structure. Duplex- and triplex-forming abilities of the
      BNA modified oligonucleotides are also described.

PMID- 12196937
TI  - First structural characterization of core modified 10,15-meso aryl
      azuliporphyrins: observation of C-H...pi interaction between pyrrole beta-CH and
      mesityl ring.
AB  - First successful syntheses and structural characterization of new core modified
      meso aryl azuliporphyrins by a simple [3 + 1] methodology are reported.

PMID- 12196938
TI  - Fusion and planarization of a quinoidal porphyrin dimer.
AB  - The crystal structure, near-infrared spectrum and electrochemistry of a quinoidal
      triply-linked porphyrin dimer are compared with those of its singly-linked
      precursor; fusing the two porphyrins planarizes the pi-system and reduces the
      optical HOMO-LUMO gap while increasing the gap between the first oxidation and
      reduction potentials.

PMID- 12196939
TI  - C-H...pi interactions in the low-temperature crystal structures of alpha,omega
      unsaturated linear hydrocarbons.
AB  - The low-temperature crystal structures of 1,7-octadiene (C8H14), 1,9-decadiene
      (C10H18), 1,7-octadiyne (C8H10) and 1,9-decadiyne (C10H14), determined following
      in situ crystal growth from the liquid, reveal the role of C-H...pi interactions
      in alpha,omega-unsaturated linear hydrocarbons in the solid state.

PMID- 12196940
TI  - Homochiral 3D lanthanide coordination networks with an unprecedented 4(9)6(6)
      topology.
AB  - Homochiral 3D metal-organic open frameworks based on enantiopure atropisomeric
      dicarboxylic acid bridging ligands and dilanthanide secondary building units
      exhibit an unprecedented 4(9)6(6) topology, and possess ethoxy-protected BINOL
      functionalities that are pointing toward the open channels.

PMID- 12196941
TI  - Interaction between tetrathiafulvalene carboxylic acid and ytterbium DO3A:
      solution state self-assembly of a ternary complex which is luminescent in the
      near IR.
AB  - Tetrathiafulvalene carboxylate associates with the charge neutral complex,
      Yb.DO3A, in methanolic solution to give rise to a novel ternary species; the
      tetrathiafulvalene unit transfers energy to the lanthanide, causing luminescence
      from the Yb metal, indicating for the first time that an electron donor
      chromophore can act as an efficient sensitiser in a self-assembled system
      containing a lanthanide acceptor.

PMID- 12196942
TI  - Synthesis of an ordered macroporous carbon with 62 nm spherical pores that
      exhibit unique gas adsorption properties.
AB  - An ordered macroporous carbon with 62 nm spherical pores was synthesized using
      colloidal-crystal templating and found to exhibit unique gas adsorption
      properties that have been so far attributed to adsorption in mesopores (size
      below 50 nm).

PMID- 12196943
TI  - Formation of a tris-capsule and a tris-carceplex from a cyclic six-bowl assembly.
AB  - A macrocycle composed of six cavitands was assembled into a tris-capsule and a
      tris-carceplex, each of which encapsulates three guest molecules.

PMID- 12196944
TI  - Ligand trans-effect: using an old concept as a novel approach to bis(dipolar) NLO
      phores.
AB  - In plane parallel arrangement and enhancement of NLO-activity are observed upon
      coordination of heteroditopic dipoles containing a phosphole ring on square
      planar d8-palladium centre.

PMID- 12196945
TI  - The first molybdenum dioxo compounds with eta 2-pyrazolate ligands: crystal
      structure and oxo transfer properties.
AB  - Molybdenum dioxo compounds [MoO2Cl(eta 2-pz)] and [MoO2(eta 2-pz)2] with pz = eta
      (2)-3,5-di-tert-butylpyrazolate have been synthesized; crystallographic data,
      catalytic activity, and oxo transfer properties are described.

PMID- 12196946
TI  - Heterosupramolecular photocatalysis: oxidation of organic compounds in nanospaces
      between surfactant bilayers formed on TiO2.
AB  - A heterosupramolecular photocatalyst consisting of TiO2 and a cationic surfactant
      bilayer formed on the surface has achieved a very high level of activity in the
      oxidation of 2-naphthol through the cooperation of the inorganic and organic
      components.

PMID- 12196947
TI  - Enantiomeric partitioning using fluorous biphase methodology for lipase-mediated
      (trans)esterifications.
AB  - Lipase-catalysed (trans)esterification reactions in homogenous perfluorocarbon
      hydrocarbon solvents enabled direct enantiomeric partitioning (up to 95% ee) of
      the products by liquid-liquid separation.

PMID- 12196948
TI  - A new one-pot three-component condensation reaction for the synthesis of 2,3,4,6
      tetrasubstituted pyridines.
AB  - The one-pot three-component condensation of a beta-ketoester, ammonia and an
      alkynone in the presence of a Bronsted or Lewis acid or Amberlyst 15 ion exchange
      resin provided 2,3,6-trisubstituted or 2,3,4,6-tetrasubstituted pyridines
      directly in good yield and with total regiocontrol.

PMID- 12196949
TI  - New direct hydroxylation of benzene with oxygen in the presence of hydrogen over
      bifunctional ion-exchange resins.
AB  - Benzene was hydroxylated directly to phenol with oxygen in the presence of
      hydrogen over Pt/Pd containing acid resins such as Amberlyst and Nafion/silica
      composites; over the latter materials the best results were obtained.

PMID- 12196950
TI  - Thia-calix[n]pyridines, synthesis and coordination to Cu(I,II) ions with both N
      and S donor atoms.
AB  - The novel thia-calix[n]pyridines (n = 3, 4, 6) coordinated to copper ions through
      nitrogen and sulfur atoms to give multinuclear complexes whose structures have
      been determined by X-ray crystallography and NMR spectra.

PMID- 12196951
TI  - Synthesis and coordination chemistry of a water-soluble verdazyl radical.
      structures and magnetic properties of M(H2O)2(vdCO2)(2).2H2O (M = Co, Ni; vdCO2 =
      1,5-dimethyl-6-oxo-verdazyl-3-carboxylate).
AB  - The synthesis of a verdazyl radical with a carboxylate substituent renders the
      radical highly soluble in water, thereby permitting the aqueous synthesis of
      Ni(II) and Co(II) verdazyl complexes which have been structurally and
      magnetically characterized.

PMID- 12196952
TI  - Supramolecular acid/base catalysis via multiple hydrogen bonding interaction.
AB  - 2-Ureidoisocytosine bearing a phosphonium ion functionality self-assembles in an
      anti-parallel manner, to exhibit a cooperative acid/base catalysis for the ring
      opening reaction of an epoxide.

PMID- 12196953
TI  - A convergent approach to 3-substituted-5-methoxyindoles. Application to the
      synthesis of melatonin [correction].
AB  - A convergent, radical based synthesis of 5-methoxyindoles including melatonin is
      described.

PMID- 12196954
TI  - Membrane disruption ability of facially amphiphilic helical peptides.
AB  - A helical 14-residue peptide containing four polar, but uncharged, benzo-21-crown
      7 side-chains aligned along one face induces significantly more vesicle leakage
      than analogous 21-mer or 7-mer peptides.

PMID- 12196955
TI  - An oxynitride, TaON, as an efficient water oxidation photocatalyst under visible
      light irradiation (lambda < or = 500 nm).
AB  - Under visible light irradiation (lambda = 420-500 nm), a tantalum oxynitride,
      TaON, functions as a stable and very efficient photocatalyst for oxidation of
      water into O2 with a sacrificial electron acceptor (Ag+).

PMID- 12196956
TI  - Nanoporous zeolite film electrodes.
AB  - Nanoporous and oriented zeolite A films have been synthesized on tin oxide
      substrates. The films can be modified to reject or pass molecular oxygen to an
      underlying electrode; films such as these show great promise for template
      assisted growth of nanostructures.

PMID- 12196957
TI  - Through-bond phosphorus-phosphorus connectivities in crystalline and disordered
      phosphates by solid-state NMR.
AB  - 2D 31P refocused INADEQUATE NMR experiments have been used to determine through
      bond P-O-P connectivities in crystalline and disordered phosphates.

PMID- 12196958
TI  - Synthesis of single crystal BaWO4 nanowires in catanionic reverse micelles.
AB  - High aspect-ratio, single crystal BaWO4 nanowires with diameters as small as 3.5
      nm and lengths up to more than 50 microns were synthesized in catanionic reverse
      micelles formed by an equimolar mixture of two surfactants: undecylic acid and
      decylamine.

PMID- 12196959
TI  - Alternate assemblies of thionine and Au-nanoparticles on an amino functionalized
      surface.
AB  - Photoactive and electroactive thionine dyes have been introduced in high-surface
      area surface-confined Au-nanoparticle superstructures by layer-by-layer
      deposition techniques.

PMID- 12196960
TI  - Nanostructured zeolite 4A molecular sieving air separation membranes.
AB  - A novel membrane forming strategy is reported to probe the intrinsic O2/N2
      selectivity of zeolite 4A membrane and to fabricate highly selective
      nanocomposite membranes by using a nanocrystal-derived hierarchical porous
      zeolite 4A membrane whose non-zeolitic mesoporsity is filled with a nonpermeable
      polymer material (polyfurfuryl alcohol).

PMID- 12196961
TI  - First syntheses of two quinoline alkaloids from the medicinal herb Ruta
      chalepensis via cyclization of an o-iodoaniline with an acetylenic sulfone.
AB  - The first syntheses of two quinoline alkaloids found in the medicinal herb Ruta
      chalepensis are reported via the conjugate addition of an o-iodoaniline to an
      acetylenic sulfone, followed by Pd-catalyzed carbonylation, intramolecular
      acylation of the corresponding sulfone-stabilized carbanion, and reductive
      desulfonylation.

PMID- 12196962
TI  - Triphenylmethyldifluoramine: a stable reagent for the synthesis of gem
      bis(difluoramines).
AB  - The conversion of ketones into geminal bis(difluoramines) can be achieved under
      mild two-phase reaction conditions by employing triphenylmethyldifluoramine as an
      in situ source of difluoramine.

PMID- 12196963
TI  - Unusual hydration behavior of dielectric loss in KA zeolite.
AB  - Two relaxations measured in dehydrated KA zeolite showed different hydration
      behaviors; the higher frequency relaxation shifted to higher frequency with
      increasing hydration whereas the lower frequency relaxation shifted to lower
      frequency; the latter behavior being contrary to present theory.

PMID- 12196964
TI  - Anion recognition and redox sensing amplification by self-assembled monolayers of
      1,1'bis(alkyl-N-amido)ferrocene.
AB  - Surface pre-organisation within robust amidoferrocene self-assembled monolayers
      can be exploited in the selective electrochemical sensing of anions in both
      organic and aqueous media.

PMID- 12196965
TI  - Sustained drug release on temperature-responsive poly(N-isopropylacrylamide)
      integrated hydroxyapatite.
AB  - A hybrid temperature-responsive hydroxyapatite-poly(N-isopropylacrylamide) (HAP
      PNIPAAm) gel has been synthesized by the interpenetration of PNIPAAm into a
      sintered HAP disk through a radical-initiated polymerization of NIPAAm monomers
      under N2 atmosphere, and shows sustained positive thermo-responsive drug release
      profile over a month at PBS buffer.

PMID- 12196966
TI  - Combinatorial approach for the hydrothermal syntheses of open-framework zinc
      phosphates.
AB  - Applying a combinatorial strategy, new zinc phosphates with interesting framework
      architectures have been hydrothermally synthesized and their structures solved by
      single-crystal X-ray diffraction analysis.

PMID- 12196967
TI  - Synthesis of open-ended MoS2 nanotubes and the application as the catalyst of
      methanation.
AB  - We report the synthesis of open-ended MoS2 nanotubes and their application as the
      catalyst for methanation of carbon monoxide with hydrogen. Because the catalysis
      of the methanation reaction occurs at relatively low temperatures, such nanotubes
      may provide new solutions toward harnessing the environmental load caused by CO
      emission.

PMID- 12196968
TI  - Two-dimensional materials based on trans-[FeII(CN)4(CO)2]2- building blocks;
      first structural evidence for a hydrated metal carbonyl ligation.
AB  - Analogues to the Hofmann-type clathrates have been characterized using trans
      [FeII(CN)4(CO)2]2- as the building blocks.

PMID- 12196969
TI  - Room temperature ionic liquids based on small aliphatic ammonium cations and
      asymmetric amide anions.
AB  - The asymmetric amide anion (CF3SO2-N(-)-COCF3) has excellent abilities to lower
      both the melting points and viscosities of room temperature ionic liquids (RTILs)
      combining with small aliphatic ammonium cations that have not yet been reported
      to form RTILs.

PMID- 12196970
TI  - HgH4 and HgH6: further candidates for high-valent mercury compounds.
AB  - Mercury tetrahydride (D4h) is calculated to have similar bond lengths and
      vibrational frequencies as the already known HgH2 and to lie energetically 200 kJ
      mol-1 above HgH2 + H2, in a local well, about 40 kJ mol-1 below a transition
      state.

PMID- 12196971
TI  - Diameter selective charge transfer in p- and n-doped single wall carbon nanotubes
      synthesized by the HiPCO method.
AB  - The unusually broad diameter distribution of single wall carbon nanotubes
      (SWCNTs) in a HiPCO derived sample made it possible to observe for the first time
      a selective loss of Raman resonances corresponding to large diameter tubes upon
      both p- (FeCl3) and n-type (K) doping.

PMID- 12196972
TI  - Multi-temporal self-organizations in 1,3-O,O'-bis(dodecyl)calix[4]arene.
AB  - After heat erases the order in 1,3-O,O'-bis(dodecyl)calix[4]arene, it self
      organizes the phenyl units into a rigid calix bowl first at T2 = 111 degrees C,
      followed by the formation of all-trans alkyl chains at T1 = 62 degrees C, which
      eventually yields a stable cone-shaped structure at room temperature.

PMID- 12196973
TI  - Monitoring the differential ordering of enantiomers included into cyclodextrins
      through deuterium NMR in lyotropic liquid crystals.
AB  - Deuterium NMR in an aqueous non-chiral liquid crystal allows the discrimination
      of enantiomers through their ordering inside beta-cyclodextrins.

PMID- 12196974
TI  - A total synthesis of phomactin A.
AB  - A total synthesis of phomactin A (1) based on a Cr(II)/Ni(II) macrocyclisation
      from the aldehyde vinyl iodide 11, leading to 12, followed by elaboration of the
      epoxyketone 16, which then undergoes spontaneous pyran-hemiacetal formation on
      deprotection, is described.

PMID- 12196975
TI  - Synthesis of open-framework zinc phosphates from organophosphorus amides.
AB  - The use of hexamethylphosphoramide as a single source of amine and phosphorus has
      made it possible to synthesize new three-dimensional zinc phosphate frameworks
      under solvothermal conditions.

PMID- 12196976
TI  - Sonoluminescence quenching by organic acids in aqueous solution: pH and frequency
      effects.
AB  - The quenching of sonoluminescence from aqueous solutions by acrylic and
      methacrylic acids is dependent on whether the acid is ionised in solution, as
      controlled by the pH, but also by the frequency of ultrasound used.

PMID- 12196977
TI  - DNA oxidation by peroxo-chromium(v) species: oxidation of guanosine to
      guanidinohydantoin.
AB  - Reactions of peroxo-chromium(v) complexes with DNA afforded mainly guanine
      oxidation yielding, a four-electron oxidation product, guanidinohydantoin, and
      exhibited extensive base labile strand scission.

PMID- 12196978
TI  - Preparation of 2,4-bis(2,4,6-tri-tert-butylphenyl)-1,3-diphosphacyclobutenes from
      2-(2,4,6-tri-tert-butylphenyl)-1-phosphaethyne and alkyllithiums.
AB  - 2-(2,4,6-Tri-tert-butylphenyl)-1-phosphaethyne was allowed to react with 0.5 eq.
      of alkyllithium to afford 2,4-bis(2,4,6-tri-tert-butylphenyl)-1,3
      diphosphacyclobutenes through an intramolecular cyclisation of a 1,3
      diphosphabuta-1,3-diene intermediate.

PMID- 12196979
TI  - Direct visualization of layer-by-layer self-assembled multilayers of
      organometallic polymers.
AB  - Direct visualization of organometallic-organic and novel all-organometallic
      multilayer superlattices prepared by layer-by-layer assembly of cationic/anionic
      polyferrocenylsilane and anionic polystyrene sulfonate polyelectrolytes using a
      gold coating/transmission electron microscopy (TEM) technique is reported.

PMID- 12196980
TI  - Development of new acid-functionalized resins for combinatorial synthesis on
      solid supports.
AB  - New methods for the synthesis of acid-functionalized polystyrene and TentaGel
      resins are described; these methods serve to overcome problems with currently
      available resins and will be instrumental in spurring the use of carboxylic acid
      resins in solid phase chemistry.

PMID- 12196981
TI  - Bridgehead alkylated 2-thiaadamantanes: novel markers for sulfurisation processes
      occurring under high thermal stress in deep petroleum reservoirs.
AB  - Two bridgehead-alkylated 2-thiaadamantanes (1,5-dimethyl and 1-methyl) have been
      identified in petroleum; these compounds give clues to sulfurisation processes
      affecting petroleum which has undergone high thermal stress.

PMID- 12196982
TI  - Asymmetric reduction of azirines; a new route to chiral aziridines.
AB  - The first enantioselective reduction of aromatic 2H-azirines yields aziridines in
      up to 70% ee, using the aminoalcohol-[RuCl2(p-cymene)]2 catalyzed asymmetric
      transfer hydrogenation reaction.

PMID- 12196983
TI  - Novel synthesis of fused isoxazolidines via a palladium catalysed allene
      insertion-intramoleculer 1,3-dipolar cycloaddition cascade reaction.
AB  - A one pot, three component palladium catalysed allenation of aryl iodides, in
      combination with a nitrone cycloaddition, leads to formation of fused
      isoxazolidines, creating two rings, two stereocentres and one tetrasubstituted
      carbon centre.

PMID- 12196984
TI  - Structure and reactivity of a novel parallel thiosulfito (SSO2-S:S') rhodium
      dinuclear complex.
AB  - The parallel thiosulfite ligand (SSO2) in a rhodium complex, which is formed by
      oxygenation of a bridging disulfide, is converted to a bridging hydrocarbyl
      thiolate ligand and sulfur dioxide gas by the reaction with hydrocarbyl halides.

PMID- 12196985
TI  - Microwave-assisted simple ion-exchange of ZSM-5-type zeolites with copper ions
      and their specific adsorption properties for N2 molecules at room temperature.
AB  - Copper ion-exchanged ZSM-5 samples, prepared using an easy method that takes
      advantage of microwaves, exhibit a quite peculiar adsorption feature for
      dinitrogen molecules, in that a large volume of chemisorbed N2 was detected, even
      at room temperature, and the specificity of the adsorption properties was
      clarified by comparing with the properties of samples prepared by an ordinary ion
      exchange method.

PMID- 12196986
TI  - Biosynthesis inspired Diels-Alder route to pyridines: synthesis of the 2,3
      dithiazolylpyridine core of the thiopeptide antibiotics.
AB  - Reaction of serine derived 1-alkoxy-2-azadienes with dehydroalanine derived
      dienophiles results in Diels-Alder reaction and aromatisation to give 2,3,6
      trisubstituted pyridines, thereby establishing the viability of the proposed
      biosynthetic route to the pyridine ring of the thiopeptide antibiotics originally
      proposed by Bycroft and Gowland.

PMID- 12196987
TI  - A novel regiospecific N to O-methyl transferase activity in the biotransformation
      of a thebaine derivative with Cunninghamella echinulata NRRL 1384.
AB  - A novel regiospecific N- to O-methyl transfer reaction has been characterised in
      the biotransformation of an N-CD3-thebaine derivative with the fungus
      Cunninghamella echinulata NRRL 1384.

PMID- 12196988
TI  - Synthesis of novel C2-aryl pyrrolobenzodiazepines (PBDs) as potential antitumour
      agents.
AB  - Three novel C2-aryl substituted pyrrolobenzodiazepines (PBDs) have been
      synthesised and evaluated in a number of cell lines revealing selective
      cytotoxicity at the sub-nanomolar level towards melanoma and ovarian cancer cell
      lines.

PMID- 12196989
TI  - A liquid-phase peptide synthesis in cyclohexane-based biphasic thermomorphic
      systems.
AB  - Combinations of typical organic solvents composed of cyclohexane and qualified
      aprotic polar organic solvents were found to realize an effective, biphasic
      thermomorphic system in arbitrary ratios of upper and lower phases that enable a
      practical application of a liquid-phase peptide synthesis.

PMID- 12196990
TI  - Dendritic cavitands: preparation and electrochemical properties.
AB  - A new series of dendrimers containing a central cavitand core with four appended
      Frechet-type dendrons, linked to the core through 4,4'-bipyridinium (viologen)
      subunits, have been synthesized, characterized and their electrochemical
      properties investigated using cyclic voltammetric measurements.

PMID- 12196991
TI  - Isolation of a new mixed valence Pt molecular oxide using phosphine as protecting
      group.
AB  - A novel tetranuclear mixed valence cationic Pt molecular oxide
      [((Me3P)2Pt)3Pt(OH)6]4+ is obtained by reacting H2Pt(OH)6 and (Me3P)2Pt2+, whose
      NMR spectra suggest the existence of another species in solution that may serve
      as a starting point for further synthesis of Pt molecular oxides.

PMID- 12196992
TI  - Tandem isomerization/Claisen transformation of allyl homoallyl and diallyl ethers
      into gamma,delta-unsaturated aldehydes with a new three component catalyst
      Ru3(CO)12/imidazolinium salt/Cs2CO3.
AB  - The three component catalyst Ru3(CO)12/1,3-bis(2,6
      diisopropylphenyl)imidazolinium chloride/Cs2CO3 (molar ratio 1:3:6) successively
      promotes both allyl to vinyl isomerization and Claisen rearrangement from allyl
      homoallyl and diallyl ethers to selectively afford gamma,delta-unsaturated
      aldehydes.

PMID- 12196993
TI  - Simplified synthesis of micropore-free mesoporous silica, SBA-15, under microwave
      hydrothermal conditions.
AB  - Synthesis of micropore-free hydrothermally stable mesoporous silica SBA-15 has
      been accomplished by templating a silica precursor (sodium
      silicate/tetraethylorthosilicate) with pluroni123 copolymer (EO20PO70EO20; M.W.
      5,800) in the presence of cosolvent (ethanol) using a minimum salt (sodium
      chloride) content, under microwave-hydrothermal conditions at 373 K in 120 mins.

PMID- 12196994
TI  - La2MgGeO6: a novel Ge based perovskite synthesised under ambient pressure.
AB  - In this communication we report the synthesis and structural characterisation of
      the new perovskite phase La2MgGeO6, which is the first example of a Ge based
      perovskite phase synthesised at ambient pressure.

PMID- 12196995
TI  - Effective recognition of H2PO4- by a new series of dendrimers functionalized with
      ferrocenyl-urea termini.
AB  - A new series of dendrimers with poly(propylene imine) backbones and 4, 8, 16, or
      32 peripheral ferrocenyl-urea groups were prepared and characterized; their
      voltammetric behavior in DMSO solution was very sensitive to the presence of
      hydrogenphosphate anions at submillimolar concentration levels.

PMID- 12196996
TI  - Fabrication of Au(111) single-crystal nanoisland-arrayed electrode ensembles by
      template-directed seeding growth.
AB  - A new and simple approach for preparation of Au(111) single-crystal nanoisland
      arrayed electrode ensembles, based on fine colloidal Au monolayer-directed
      seeding growth, is reported.

PMID- 12196997
TI  - Light mediated cofactor recycling system in biocatalytic asymmetric reduction of
      ketone.
AB  - Reduction of an artificial ketone by Synechococcus elongatus PCC 7942 proceeds
      smoothly by the aid of light. The efficiency of the reaction is very high since
      the coenzyme NADPH is regenerated by using light energy.

PMID- 12196999
TI  - A rapid method of synthesizing the layered titanosilicate JDF-L1.
AB  - A rapid procedure for synthesis of highly crystalline and pure samples of JDF-L1
      without using organics are reactants or templates is described and indexation of
      the powder X-ray diffraction pattern of this phase is presented.

PMID- 12196998
TI  - Synthesis of a porphyrin-labelled carboranyl phosphate diester: a potential new
      drug for boron neutron capture therapy of cancer.
AB  - A boron-rich, water-soluble porphyrin conjugate was synthesized by coupling of
      two carboranyl alcohols with 2-chlorophenoxyphosphorus dichloride, followed by
      conjugation to an amine-functionalized tetraphenyl-porphyrin via an amide
      linkage.

PMID- 12197000
TI  - A new supramolecular system of racemic-bis-beta-naphthol, benzoquinone and
      aromatic hydrocarbon, which shows high molecular recognition ability.
AB  - Racemic-bis-beta-naphthol, benzoquinone and aromatic hydrocarbons formed a new
      three component supramolecular system as black crystals. X-ray analysis of the
      crystals shows that (+)- and (-)-bis-beta-naphthol and benzoquinone form a
      quinhydrone-type crystalline lattice with aromatic stacking and hydrogen bonding
      in which the third aromatic hydrocarbon component is accommodated. As the cavity
      created has a definite shape and size, only hydrocarbons which fit the cavity are
      selectively included.

PMID- 12197001
TI  - High resolution imaging of functional group distributions on carbon surfaces by
      tapping mode atomic force microscopy.
AB  - Here we report, for the first time, the high resolution imaging of hydrophilic,
      polar functional group distributions on flat carbon surfaces by phase contrast in
      noncontact tapping mode AFM.

PMID- 12197002
TI  - 1,5-Bis(benzothiazolyl)-3-thiapentane and its asymmetric dinuclear Ag(I) complex
      with three distinct intermolecular-stacking interactions.
AB  - Synthesis of a dibenzothiazole thioether ligand that coordinates Ag(I) yielding
      an asymmetric dinuclear complex with three unique intermolecular pi-stacking
      interactions, which influence the first coordination spheres of the silver
      centers, is reported.

PMID- 12197003
TI  - The chair of anatomy in the Faculty of Medicine at Strasbourg: 350th anniversary
      of its foundation (1652-2002).

PMID- 12197004
TI  - Vascularization of the palate in maxillary osteotomies: anatomical study.
AB  - Le Fort 1 maxillary osteotomy carries a risk of injury to the descending palatine
      arteries which vascularize the bulk of the mucosa of the bony palate. Some
      authors believe that injury to these arteries in the greater palatine canal is
      intrinsic to the procedure without any consequence for the trophicity of the
      mucosa or bony palate. In order to assess the risk of injury to the descending
      palatine arteries during such surgery, and to demonstrate the supplementary
      vascularization which would avoid ischemia of the palate, we carried out a study
      of the vascularization of the palate on 11 fresh cadavers. We used intra-arterial
      injection of colored latex and dissection of the vessels running to the palate.
      The study was done without osteotomy in the first subject, after a Le Fort 1
      osteotomy in the five following subjects and after a Le Fort 1 osteotomy and
      ligation of the two descending palatine arteries in the last five subjects. Our
      results show that injury of the descending palatine arteries is not intrinsic to
      the procedure in spite of mobilization of the palatine plateau. When the
      descending palatine arteries are ligated there is diminution in coloration of the
      mucosa of the bony palate but there is substitution by the arteries vascularizing
      the soft palate, essentially the ascending palatine artery and the pharyngeal
      branch arising from the ascending pharyngeal artery. However, this substitute
      vascularization has individual variations.

PMID- 12197005
TI  - Innervation of the abductor digiti minimi muscle of the human foot: anatomical
      basis of the entrapment of the abductor digiti minimi nerve.
AB  - The origin, relationships and innervation of the abductor digiti minimi muscle
      were determined in 145 human feet, from formaldehyde-fixed cadavers. The muscle
      arises from both processes of the calcaneal tuberosity, from the plantar
      aponeurosis and from the septum which separates it from the flexor digitorum
      brevis muscle. The nerve to the abductor digiti minimi muscle arises next to the
      origin of the lateral plantar nerve, close to the abductor hallucis muscle, and
      descends becoming closely related to the medial face of the calcaneus and the
      deep face of the abductor hallucis muscle. Then, it passes inferiorly through the
      origin of the quadratus plantae muscle and later divides into two branches for
      the two heads of the muscle.

PMID- 12197006
TI  - Size of the collateral intercostal artery in adults: anatomical considerations in
      relation to thoracocentesis and thoracoscopy.
AB  - No detailed descriptions exist of the collateral intercostal artery which can
      provide an accurate anatomical basis for ensuring a low rate of vascular
      complications during thoracocentesis and thoracoscopy. Consequently the present
      study was undertaken to provide information on the origin, size and topographic
      relationships of the collateral intercostal artery. Ninety cadaveric adult
      intercostal spaces were dissected using standard procedures. The collateral
      intercostal arteries were exposed throughout their full length and measured at
      the points within the intercostal spaces considered to be the most important for
      clinical purposes. The posterior intercostal arteries and their collateral
      branches were observed to decrease in size from posterior to anterior; however,
      no significant differences were present in their size in the first four
      intercostal spaces. Based on these findings the usual thoracocentesis or
      thoracoscopy technique, in which it is recommended that puncture is done as close
      as possible to the superior margin of the inferior rib, may lead to collateral
      intercostal artery laceration and considerable bleeding. A subtle, but important,
      modification to this technique is suggested aimed at achieving safer access to
      the intercostal space. In the modified technique, the puncture should be made in
      the middle of the intercostal space, thereby reducing the possibility of
      laceration of the collateral intercostal artery.

PMID- 12197007
TI  - Microvascularization of the mucocutaneous junction of the nose.
AB  - The aim of this study was to describe the microvascularization of the area of
      junction located between the integuments of the nasal ala and the respiratory
      mucosa. This study is part of an overall study on the microvascularization of the
      mucocutaneous junctions of the head. It was undertaken on histological or
      clarified sections of noses from fetuses, newborns and adults whose vascular
      system was injected with Indian ink agar. The mucocutaneous junction of the nose
      shows similarities with the mucocutaneous junction of the oral cavity. Under a
      well-defined avascular and thick epithelium lies a vascular papillary network
      with typical loops less high than in the lips. The angioarchitectonics of
      superficial and deep vascular reticular networks is similar to that of the lips
      but they are less dense.

PMID- 12197008
TI  - Pubourethral ligaments in women: anatomical and clinical aspects.
AB  - The anatomy and histological structure of the proximal (PPUL), distal (DPUL) and
      intermediate (IPUL) pubourethral ligaments in women was examined to improve the
      understanding of their roles in female urethral physiology. An anatomical study
      of the pelvis was carried out in 10 adult female cadavers (60-102 years), the
      pelvis being removed and frozen prior to dissection. The pubourethral ligaments
      (PUL) were dissected in sagittal sections in seven specimens and in a frontal
      section in one specimen; the remaining two pelves were dissected using a
      hypogastric approach. The location, insertion, direction and histological
      structure of the ligamentous structures were studied. The PUL were identified in
      all 10 dissections, being paired, symmetrical, pearly-white, fibrous and
      resistant to stretching. The bony (parietal) insertion was variable on the
      posterior surface of the pubis, while the visceral insertion was located on the
      dorsal aspect of the proximal third of the urethra and neck of the bladder for
      the PPUL and on the distal third of the urethra for the DPUL. Histologically, the
      ligaments were composed of dense collagen fibres and bundles of axially
      orientated smooth muscle fibres. The PPUL was closely associated with the
      sphincter urogenitalis muscle, whereas the DPUL appeared to reinforce the role of
      the compressor urethra. It is suggested that the PUL plays an effective role in
      passive and active suspension of the urethra. The pubourethral ligaments are a
      constant anatomical entity which should be spared in urethral surgery in women in
      order to ensure an intact urogenital sphincter.

PMID- 12197009
TI  - Topographical analysis of lymphatic pathways from the meso- and hypopharynx based
      on minute cadaveric dissections: possible application to neck dissection in
      pharyngeal cancer surgery.
AB  - To facilitate the development of new operative procedures for pharyngeal cancer,
      it is important to understand the precise location of the lymph nodes and their
      pathways. Minute dissection of 22 neck-halves (11 adult cadavers) was undertaken
      to determine the location and topographical relationships of the lymphatics of
      the pharynx. Four groups of lymph nodes on the drainage pathways from the meso-
      and hypopharynx to the internal jugular nodes were classified according to their
      topographical relationships to the carotid arteries: lateral pharyngeal, superior
      thyroid, lateral retropharyngeal and medial retropharyngeal nodes. Lymphatics
      from the mesopharynx passed laterally to lateral pharyngeal or jugulodigastric
      nodes or slightly upward to lateral retropharyngeal nodes. Lymphatic drainage
      from the hypopharynx was multidirectional with the pathways being classified as
      follows: ascending pathway to the lateral pharyngeal and lateral retropharyngeal
      nodes, lateral pathway to the internal jugular chain, and descending pathway
      connecting to the uppermost vessels ascending from the recurrent laryngeal nerve
      chain. In addition, a contralateral pathway was found originating from the
      hypopharynx extending to the contralateral internal jugular chain. These findings
      provide valuable information for comparison with CT and MRI studies, as well as
      with clinicopathological data, to clarify the precise mode of metastasis in head
      and neck cancers. These results are also applicable to neck dissection in meso-
      and hypopharyngeal cancers.

PMID- 12197010
TI  - Double tendons at the distal attachment of the extensor hallucis longus muscle.
AB  - The distal attachments of the extensor hallucis longus (EHL) tendons in 47
      amputated legs and in eight cadavers were examined. The EHL had two tendons in 34
      of the amputated legs and bilaterally in five cadavers. The lateral tendon was
      inserted to the middle of the dorsal aspect of the base of the distal phalanx of
      the hallux and the medial tendon to the medial side of the insertion of the
      lateral tendon. The length and thickness of these two tendons were measured and
      compared in order to obtain data for using these tendons in tendon repair and
      hallux varus corrections by autogenous tendon transfer surgery. Additionally, on
      the right foot of one of the cadavers, it was observed that the extensor hallucis
      brevis tendon united with the lateral tendon of the EHL. We recommend that foot
      ankle surgeons be aware of the various accessory EHL tendons and their potential
      use in problematic cases.

PMID- 12197011
TI  - Lumbar hernia: anatomical route assessed by computed tomography.
AB  - Lumbar hernia is classically described as arising from the superior (Grynfeltt's)
      lumbar triangle or the inferior (Jean-Louis Petit's) lumbar triangle. The present
      anatomical study based on a computed tomography examination performed in a
      patient with lumbar hernia, has led to the suggestion that lumbar hernias cross
      the lumbar wall through a musculoaponeurotic tunnel, whose deep and superficial
      openings are the superior and inferior lumbar triangles, respectively.

PMID- 12197013
TI  - A detailed anatomical description of the subvastus region and its clinical
      relevance for the subvastus approach in total knee arthroplasty.
AB  - The subvastus region and its anatomical contents are important when performing a
      total knee replacement via a subvastus approach. Thirty-two human cadaver thighs
      were studied to provide a detailed anatomical description of the subvastus region
      and its contents, namely the descending genicular artery and its branches, and
      the saphenous nerve proximally. In 24 specimens the descending genicular artery
      arose from the femoral artery and divided into osteoarticular and saphenous
      branches, while in eight specimens it was absent. The osteoarticular and
      saphenous branches arose independently from the femoral artery. On the basis of
      these distribution patterns nine variations with regard to the number and origin
      of the muscular, musculoarticular and saphenomusculoarticular branches arising
      from these vessels could be identified. The musculoarticular branch should be
      preserved wherever possible; however, if it must be sacrificed to improve
      exposure of the knee joint via a proximal extension of the incision, the passage
      of the saphenous nerve and the saphenous branch through the vastoadductor
      membrane are additional structures which must be considered. The proximal
      limitation for the mobilisation is the adductor hiatus, with further mobilisation
      increasing the risk of damaging the femoral artery and vein.

PMID- 12197012
TI  - Anatomy of verbal memory: a functional MRI study.
AB  - The recent advent of new functional neuroimaging techniques such as functional
      magnetic resonance imaging (fMRI) makes it possible to examine cerebral
      activations in healthy individuals. In the present study, we attempted to examine
      the anatomical distribution of neocortical and mediotemporal activations in
      control subjects during episodic memory tasks over 24 h. BOLD (blood oxygenation
      level-dependent) fMRI data were collected from 10 control subjects. Twenty-two
      contiguous images covering the whole brain were acquired using an EPI echoplanar
      sequence. Subjects were instructed to learn a list of 17 words, and to recall it
      immediately and after a 24-h interval. Individual and group analyses were
      performed using SPM96. The results demonstrated that a similar left occipito
      temporofrontal network was activated during both immediate and 24-h-delayed
      retrieval conditions. In addition, the 24-h-delayed retrieval also activated a
      larger parietal region and the right hippocampus. These findings suggest that
      fMRI is a reliable method with which to perform anatomical studies.

PMID- 12197014
TI  - Clinical implications of left ovarian vein incomplete duplicity with embryonic
      intersubcardinal anastomosis-derived branches.
AB  - During the dissection of a female human cadaver a case of a duplex ovarian vein
      was observed. It was unique in its upper course where it anastomosed with an
      inferior polar renal vein, which in turn was linked to an upper polar renal vein
      by means of a joining branch. It is hypothesised that this represent a persistent
      link between the left subcardinal vein and the left sacrocardinal vein, together
      with some branches of a venous net, which represent the embryological
      intersubcardinal anastomosis. The gonadal vein arises from the distal (or
      postrenal) left subcardinal vein portion; the left renal vein develops from the
      intersubcardinal anastomosis. The venous net derived from the intersubcardinal
      anastomosis may represent a bypass system in cases of left renal vein occlusion.
      Left gonadal vein duplicity may also play an important role in the anatomical
      basis of idiopathic left ovarian vein syndrome or left varicocele, and can lead
      to mistakes being made during venous sclerotherapy.

PMID- 12197015
TI  - Multiple variations in the azygos venous system: a preaortic interazygos vein and
      the absence of hemiazygos vein.
AB  - Multiple variations of the azygos venous system were detected during routine
      dissection. The hemiazygos vein was underdeveloped. On the left side of the
      thorax, posterior intercostal veins between the 8th and 11th intercostal spaces
      and the subcostal vein drained into the azygos vein independently. In addition,
      the posterior 4th, 5th, 6th and 7th intercostal veins united and formed two
      superior and inferior trunks. The superior common trunk, at the level of the T4
      vertebra, crossed the vertebral column obliquely, lying anterior to the aorta and
      posterior to the esophagus, opening into the azygos vein at the level of the T4
      vertebra. The other structures in this part were normal. There were different
      courses of the azygos vein system. This variation is important in mediastinal
      surgery and also in the interpretation of radiographs.

PMID- 12197016
TI  - The third occipital condyle, a constituent part of a median occipito-atlanto
      odontoid joint: a case report.
AB  - A compound conjunction between basiocciput, atlas (anterior arch), and dens of
      axis (odontoid process) was found incidentally during routine dissection of the
      head of an 83-year-old man. According to the patient's history, no neck
      disability had been recorded. A median saw-cut of the head-and-neck conjunction
      revealed that the basion was anteriorly reinforced by an osseous pillar 4 mm in
      length and 3 mm in width. Such a formation is known as a third occipital condyle
      (condylus tertius, CT). In our case it exhibited one surface oriented in an
      anterior-inferior direction and articulating with the superior border of the
      anterior arch of the atlas, and another surface oriented in a posterior-inferior
      direction and articulating with the superior portion of the dens of axis. The
      dens of axis itself articulated with the anterior arch of the atlas, forming the
      (normal) median atlanto-axial joint. Post-mortem computed tomography and post
      mortem histological examination completed the investigation. The cartilage of the
      articular compartment between the CT and the anterior arch of the atlas and the
      related anterior fibrous disc exhibited severe arthrosis. The findings were
      discussed in the light of developmental and comparative anatomy.

PMID- 12197017
TI  - Anatomical variations of the inguinal nerves and risks of injury in 110 hernia
      repairs.
AB  - The aim of this study was to identify the anatomical variations in the inguinal
      course of the ilioinguinal nerve (IIN) and the iliohypogastric nerve (IHN) during
      operative repair of inguinal hernias. A consecutive series of 110 primary
      inguinal hernias were repaired by the mesh technique. Particular attention was
      paid to early identification and recording of the course of both the IIN and IHN
      and preserving them throughout the operative procedure. The course of both nerves
      was found to be consistent with that described in anatomical texts in only 46 of
      110 explorations (41.8%). The course of one or both nerves was found to be a
      variant in the other 64 of 110 (58.2%) explorations and often rendered them
      susceptible to injury. These variations included: (1) acute infero-lateral
      angulation of the IIN at its exit behind the superficial inguinal ring (SIR)
      fibers in 20 of 64 cases; (2) similar direction of the IIN but in a plane
      superficial to the external oblique aponeurosis (EOA) and proximal to the SIR in
      18 of 64 cases; (3) a single stem for both nerves over the spermatic cord in 24
      of 64 cases, with variation in the subsequent course; (4) absence of one or both
      nerves in 8 of 64 cases; (5) accessory IIN or IHN in 3 of 64 cases; and (6)
      aberrant origin of the IIN from the genitofemoral nerve (GFN) in 2 of 64 cases.
      None of 68 of 105 patients seen at 3 months postoperatively (compliance rate 65%)
      complained of sensory disturbances or pain in a dermatome distribution of the IIN
      or IHN. It is concluded that anatomical variations in the inguinal course of the
      IIN and the IHN are extremely common but readily identifiable. Their early
      identification and preservation is likely to abolish, or considerably decrease,
      the incidence of postoperative sensory changes and/or neuralgia pain.

PMID- 12197018
TI  - Study of the relationship between the suprascapular artery and the brachial
      plexus.
AB  - The literature concerning the relationship of the suprascapular artery with the
      brachial plexus is quite limited. The aims of this study were to investigate the
      different types of relationships between the suprascapular artery and the
      brachial plexus trunks and to try to clarify their prevalence in the European
      population. Our study involved the dissection of 100 upper extremities from
      adults, all of European origin (55 women, 45 men). In the classic description,
      the suprascapular artery passes in front of the brachial plexus (group A) in the
      majority of cases, then behind the omohyoid before reaching the superior border
      of the scapula. There are two other types of relationship with the brachial
      plexus: the suprascapular artery can pass between the trunks of the brachial
      plexus (group B) or the artery can pass behind the brachial plexus (group C). To
      our knowledge there has been only one study on the subject, carried out by Kosugi
      et al. Our results show a not inconsiderable number of variations in the
      relationships between the suprascapular artery and the brachial plexus (29%).
      Although no differences were noted between the sexes, a significant number of
      individual variations were revealed by the comparative study of dissections
      performed on both upper extremities of the same individual. Our results suggest
      that new studies are required to complete these initial anatomical results
      observed on a small sample of subjects of European origin. The French version of
      this article is available in the form of electronic supplementary material and
      can be obtained by using the Springer LINK server located at
      http://dx.doi.org/10.1007/s00276-002-0026-5.

PMID- 12197019
TI  - Nervous branch passing through an accessory canal in the sphenozygomatic suture:
      the temporal branch of the zygomatic nerve.
AB  - A nervous branch which passes through a small canal in the sphenozygomatic suture
      is sometimes observed during dissection. To examine the origin, course and
      distribution of this nervous branch, 42 head halves of 21 Japanese cadavers (11
      males, 10 females) and 142 head halves of 71 human dry skulls were used. The
      branch was observed in seven sides (16.7%); it originated from the communication
      between the lacrimal nerve and the zygomaticotemporal branch of the zygomatic
      nerve or from the trunk of the zygomatic nerve. In two head halves (4.8%), the
      branch pierced the anterior part of the temporalis muscle during its course to
      the skin of the anterior part of the temple. The small canal in the suture was
      observed in 31 head halves (21.8%) of the dry skulls. Although this nervous
      branch is inconstantly observed, it should be called the temporal branch of the
      zygomatic nerve according to the constant positional relationship to the sphenoid
      and zygomatic bones. According to its origin, course and distribution, this
      nervous branch may be considered to be influential in zygomatic and retro-orbital
      pain due to entrapment and tension from the temporalis muscle and/or the narrow
      bony canal. The French version of this article is available in the form of
      electronic supplementary material and can be obtained by using the Springer LINK
      server located at http://dx.doi.org/10.1007/s00276-002-0027-4.

PMID- 12197020
TI  - A beaklike bony extension of the medial aspect of the greater sciatic notch: a
      radiographic appearance sexually influenced.
AB  - The bony pelvis provides more obvious sex differences than any other bone in the
      human skeleton. This study evaluates a bony extension of the medial aspect of the
      greater sciatic notch, which extends caudad to the arcuate line as seen on pelvic
      radiographs. A total of 2620 randomly selected supine pelvic radiographs
      (anteroposterior view) of adult females and males were reviewed. The subjects
      belonged to a central Anatolian population and their age ranged between 18 and 77
      years in females and between 18 and 81 years in males. Only 22 (1.7%) of the 1337
      female pelvic radiographs showed a bony extension, whereas 882 (68.8%) of the
      males had one. All these bony extensions were bilateral and symmetric. The
      results were statistically significant (P < 0.001). We assert that this
      radiographic appearance is a male characteristic.

PMID- 12197021
TI  - An MRI study of the meniscofemoral and transverse ligaments of the knee.
AB  - Our aim was to assess the anatomic localization, dimensions and incidence of the
      transverse and meniscofemoral ligaments, which can show anatomic variations or be
      mistaken for some pathologic conditions. In 100 healthy subjects (52 female, 48
      male) whose ages ranged from 12 to 84 years, sagittal and coronal magnetic
      resonance images of the knee were obtained. There was at least one anterior or
      posterior meniscofemoral ligament in 82 cases. The anterior meniscofemoral
      ligament was present in 8 of the female and 4 of the male subjects. The posterior
      meniscofemoral ligament was found in 20 female and 22 male subjects. Both the
      anterior and posterior meniscofemoral ligaments were present in 15 female and 13
      male subjects. The transverse ligament of knee was encountered in 19 female and
      12 male subjects. In the females, average lengths of the anterior and posterior
      meniscofemoral ligaments were 9.87 +/- 4.79 mm and 25.60 +/- 5.50 mm,
      respectively. The corresponding values in the males were 11.11 +/- 2.57 mm and
      28.80 +/- 5.49 mm, respectively. In the females, average width of the anterior
      and posterior meniscofemoral ligaments were 2.45 +/- 1.02 mm and 2.30 +/- 1.15
      mm, respectively. The corresponding values in the males were 2.52 +/- 0.87 mm and
      2.30 +/- 1.15 mm, respectively. On MRI assessment, in order to differentiate
      intra-articular lesions such as osteochondral and meniscal fragments or
      pseudotear of the lateral meniscus from the normal ligamentous anatomy of knee,
      the orientation and characteristic localization of the meniscofemoral ligaments
      should be taken into account. The French version of this article is available in
      the form of electronic supplementary material and can be obtained by using the
      Springer LINK server located at http://dx.doi.org/10.1007/s00276-002-0023-8.

PMID- 12197022
TI  - Multiple arterial variation of the human upper limb.
AB  - A case report of multiple variations involving the arteries of the upper limb in
      a single cadaver is presented. In addition to the proximal origin of the arteries
      unusual arterial patterns on both the right and left sides were present. On the
      right side, the subscapular artery gave rise to a large posterior circumflex
      humeral artery in addition to the thoracodorsal and circumflex scapular arteries.
      On the left side, the radial and ulnar arteries arose from the brachial artery at
      the level of arm, with their origins being opposite to the usual arrangement.
      There was an arciform anastomosis between the radial and ulnar arteries, with the
      radial recurrent artery arising from the concavity of the arch. The course of
      both the radial and ulnar arteries was normal at the wrist and hand, except for
      the absence of the first palmar metacarpal artery and an early bifurcation of the
      second palmar metacarpal artery. The French version of this article is available
      in the form of electronic supplementary material and can be obtained by using the
      Springer LINK server located at http://dx.doi.org/10.1007/s00276-002-0011.

PMID- 12197023
TI  - High duplication of the internal jugular vein: clinical incidence in the adult
      and surgical consequences, a report of three clinical cases.
AB  - Duplication of the internal jugular vein (IJV) is a rare malformation. Three
      intraoperative cases are reported. In our personal experience, the clinical
      incidence of the anomaly is approximately 4 per 1,000 unilateral neck
      dissections. The venous duplication is at a variable height, affecting the
      superior part of the IJV. The lateral branch of the accessory nerve (XI) always
      passes medially to the anterior vein and laterally to the posterior vein, between
      the venous duplication. This is most often unilateral but sometimes bilateral.
      The IJV may be normal, dilated or ectatic. The discovery of this anatomical
      variation has practical implications during cervical lymph node clearance, either
      functional or radical, during oncological surgery necessitating viewing the IJV
      and its affluents and the lateral branch of the accessory nerve. The
      embryological explanation suggests a topographical "conflict" between the
      development of the IJV and the lateral branch of the accessory nerve. The French
      version of this article is available in the form of electronic supplementary
      material and can be obtained by using the Springer LINK server located at
      http://dx.doi.org/10.1007/s00276-002-0020-y.

PMID- 12197024
TI  - Anatomical study of the blood supply of the coxal bone: radiological and clinical
      application.
AB  - The aim of this work was to study the arterial blood supply of the coxal bone in
      order to optimize radiological embolization and to minimize the risk of
      postoperative osteonecrosis. Ten fresh cadavers were dissected after intra
      arterial injection of colored resin. All the collateral vessels running to this
      bone were described and counted. On 25 dry bones, the vascular foramina were
      measured with the aid of a millimetric gauge and a vascular map was created. The
      posterior part of the ilium appears to be twice as well vascularized as the
      anterior part. Fractures of the posterior arch of the pelvis are theoretically
      more hemorrhagic. The presence of the iliolumbar artery in contact with the
      sacroiliac joint increases the risk with open book or shearing fractures. The
      artery of the ischium, a collateral of the pudendal artery, supplies the
      posterior and lateral parts of the acetabulum and the artery of the roof of the
      acetabulum, its superior and lateral parts. The branches of the anterior and
      posterior divisions of the obturator artery supply the superior part of the
      surroundings of the obturator foramen and the antero-inferior and postero
      inferior parts of the acetabulum. The Kocher approach may injure the artery of
      the ischium. Letournel's extended lateral approach and Mears' triradiate approach
      may injure the artery of the ischium and the artery of the roof of the
      acetabulum. The risk of osteonecrosis appears to be theoretically increased if
      one adds an endopelvic approach. The anterior approach to the acetabulum appears
      to be that which theoretically leads to the least devascularization. The French
      version of this article is available in the form of electronic supplementary
      material and can be obtained by using the Springer Link server located at
      http://dx.doi.org/10.1007/s00276-002-0029-2.

PMID- 12197025
TI  - The cutaneo-lymph node flap of the superficial circumflex artery.
AB  - Upper limb lymphoedema and associated radiation-damaged chest wall are
      complications occurring after breast cancer treatment. Previous anatomical and
      clinical studies have demonstrated the usefulness of inguinal lymph node
      autotransplantation in managing lymphoedema. The present anatomical study is a
      complement to previous studies about the cutaneous inguinal flap. It has
      demonstrated the feasibility of using a free inguinal cutaneo-lymph node flap
      supplied by the superficial circumflex iliac artery. The useful vascularized
      abdominal skin area ranged from 176 to 288 cm2 and was contained within a
      vascularized skin area extending up to 928 cm2. However, the vascularization
      never extended widely beyond the abdominal midline line. Although it mainly
      remains unilateral, this flap combining skin and lymph nodes may help in the
      management of lymphoedema and chest wall damage when they occur simultaneously as
      complications of breast cancer treatment. The French version of this article is
      available in the form of electronic supplementary material and can be obtained by
      using the Springer LINK server located at http://dx.doi.org/10.1007/s00276-002
      0024-7.

PMID- 12197026
TI  - Intramuscular distribution of nerves in the human triceps surae muscle:
      anatomical bases for treatment of spastic drop foot with botulinum toxin.
AB  - Recent progress has been made in selective functional treatment of hypertonia of
      spastic origin by local injection of botulinum toxin into the muscles responsible
      for equinus foot dynamic deformation. The technical aspect of the intervention
      requires a strategy adapted to the individual patient. Good practice is founded
      on precise knowledge of the intramuscular nerve distribution of end plate zones,
      since the target organ of the toxin is the motor end plate. Knowledge about the
      location of motor end plates, which differs according to the structure of the
      muscle in question, remains rather poor. Through macroscopic and stereoscopic
      microscopic dissection of the nerve courses in the triceps surae muscular group
      in 40 legs, we have ascertained in more detail the distribution of motor end
      plates, which appear to be more numerous in certain zones of the muscle bellies.
      These zones were measured morphometrically and divided into segments which are
      expressed in percentages of a standard leg length. We maintain that these zones
      are the injection sites most likely to guarantee the best treatment efficacy.

PMID- 12197027
TI  - Microvascularization of the mucocutaneous junction of the eyelid in fetuses and
      neonates.
AB  - The aim of this study was to specify the microvascularization of the junctional
      region between the integuments of the superficial surface of the free margin of
      the eyelid and the palpebral conjunctival mucosa. The study was carried out using
      histological or transparified slices of upper and lower eyelids taken from
      fetuses and neonates, in which the vascular system was injected with agarized
      China ink. The mucocutaneous junction of the eyelid is located at the posterior
      border of the free margin and extends to its deep surface. It has vascular
      similarities to the oral cavity and the nasal pyramid. Under a thickened
      avascular epithelium, there is a papillary network composed of characteristic
      loops that are less raised than in the lips but more developed than in the nose.
      The superficial and deep vascular reticular networks are comparable in
      fundamental arrangement to those of other junctional zones. Thus, the palpebral
      mucocutaneous junction shows cutaneous-type microvascularization, just like the
      other junctional zones of the head.

PMID- 12197029
TI  - Medicare. Policy or politics?

PMID- 12197028
TI  - Cost containment. Up and away.

PMID- 12197030
TI  - Quality of care. Intensivist pain.

PMID- 12197031
TI  - Practice what you preach?

PMID- 12197032
TI  - Finance. Seeking disclosure.

PMID- 12197033
TI  - 1Q[3a]. Are CON laws relevant again as niche facilities multiply?

PMID- 12197034
TI  - 9/11/02. Select where you'll observe this day with care.
AB  - This may be one anniversity best marked by staying at home, not out of fear of
      terror ro frustration over security hassels, but to stand in pride and solidarity
      among those we love.

PMID- 12197035
TI  - Navigating the niche. Three markets respond to the influx of specialty facilities
      -Indianapolis, Phoenix, Columbus.
AB  - Specialty centers that focus on lucrative services such as cardiology and
      orthopedics pose a challenge to full-service hospitals in already crowded health
      care markets. We examine how hospitals in three markets have responded, from
      aggressively working to keep niche facilities from gaining a foothold to
      partnering with physicians on their own centers.

PMID- 12197038
TI  - Calming the IT seas. New alliance to guide health care toward technology
      standards.
AB  - Thirty-five founding members have launched the National Alliance for Health
      Information Technology to develop voluntary interoperability standards for IT. In
      the process, the alliance hopes to encourage the health care industry to pick up
      the pace in adopting new technologies that will improve quality and operating
      performance.

PMID- 12197039
TI  - The health care workforce. State-by-state numbers and initiatives.
AB  - As the shortage of health care workers intensifies, its impact is becoming more
      and more obvious. From overcrowded emergency departments to the cancellation of
      elective surgeries, providers and others are starting to recognize the effect on
      patient care, and to realize that the situation is likely to get worse before it
      gets better. H&HN examines the distribution of the health care workforce
      throughout the United States, the extent of the shortage in certain professions
      and how some states are responding.

PMID- 12197040
TI  - The American Hospital Quest for Quality Prize.
AB  - Improving the quality and safety of health care requires dedicated leadership and
      the involvement of everyone who affects care within an organization, from
      trustees and administrators to physicians, nurses and frontline staff. To honor
      organizations that have made exceptional improvements in quality and patient
      safety, the American Hospital Association, along with McKesson Corp. and McKesson
      Foundation, established The American Hospital Quest for Quality Prize: honoring
      leadership and innovation in patient care quality, safety and commitment. The
      award recognizes hospitals and health systems that have created measurable and
      sustainable quality and patient safety programs. Among other things, the
      organization must have a blame-free work environment and systems in place to help
      identify actual and potential adverse events and solutions to improve them. As
      the winner of the inaugural Quest for Quality Prize, Missouri Baptist Medical
      Center, Town and Country, Mo., received $75,000 to further its safety and quality
      efforts. Two finalists--Children's Hospitals and Clinics, Minneapolis/St. Paul,
      Minn., and Fairview Hospital, Great Barrington, Mass.--each received a $12,500
      award. A Citation of Merit was presented to Brigham and Women's Hospital, Boston.

PMID- 12197044
TI  - Real people. When hospital trustees speak, lawmakers listen to a community
      perspective.
AB  - Because they have no economic stake in the hospitals they serve, trustees can be
      most effective in bringing the community's health care perspective to their
      legislators' attention.

PMID- 12197045
TI  - [Petroleum chemical plant of Porto Marghera: epidemiology and prevention].

PMID- 12197046
TI  - [Preventing Alzheimer's disease through a change in diet: a feasible research].

PMID- 12197047
TI  - [Western diet and Alzheimer's disease].
AB  - Alzheimer Disease, characterised by a global impairment of cognitive functions,
      is more and more common in Western societies, both because of longer life
      expectancy and, probably, because of increasing incidence. Several hints suggest
      that this degenerative disease is linked to western diet, characterised by
      excessive dietary intake of sugar, refined carbohydrates (with high glycaemic
      index), and animal product (with high content of saturated fats), and decreased
      intake of unrefined seeds--cereals, legumes, and oleaginous seeds--and other
      vegetables (with high content of fibres, vitamins, polyphenols and other
      antioxidant substances, phytoestrogens) and, in several populations, of sea food
      (rich in n-3 fatty acids). It has been hypothesised, in fact, that AD, may be
      promoted by insulin resistance, decreased endothelial production of nitric oxide,
      free radical excess, inflammatory metabolites, homocysteine, and oestrogen
      deficiency. AD, therefore, could theoretically be prevented (or delayed) by
      relatively simple dietary measures aimed at increasing insulin sensitivity
      (trough reduction of refined sugars and saturated fats from meat and dairy
      products), the ratio between n-3 and n-6 fatty acids (e.g. from fish and
      respectively seed oils), antioxidant vitamins, folic acid, vitamin B6,
      phytoestrogens (vegetables, whole cereals, and legumes, including soy products),
      vitamin B12 (bivalve molluscs, liver), and Cr, K, Mg, and Si salts. This
      comprehensive improvement of diet would fit with all the mechanistic hypotheses
      cited above. Several studies, on the contrary, are presently exploring
      monofactorial preventive strategies with specific vitamin supplementation or
      hormonal drugs, without, however, appreciable results.

PMID- 12197048
TI  - [Supply of outpatient care in the Lazio region: geographic distribution and
      characteristics of outpatient clinics].
AB  - Outpatient care accounts every year for a large share of the National Health Fund
      spending, however characteristics of supply have not been thoroughly
      investigated. Objective of the study is the description of the outpatient care
      system of Lazio region and of the main characteristics of outpatient clinics,
      through indicators obtained using data from the Outpatient Care Information
      System (SIAS) for 1999. Outpatient clinics were classified into three categories:
      ASL managed clinics, private clinics and hospital trusts. Absolute and relative
      density of supply (respectively DAO and DRO) were used as indicators of clinics
      distribution in the regional area. Number of specialties, average procedure
      weight and volume of procedures performed were used as indicators of complexity.
      Absolute density of supply (DAO = n. of dispatch points/population) is generally
      high, and a large and statistically significant variability is observed (p <
      0.001). The relative density (i.e. the correlation coefficient between DAO and
      population density) is positive overall (r = 0.43), but it is higher within the
      private sector (r = 0.62) independently from provider category. Statistically
      significant differences were observed among categories of providers in terms of
      average number of specialties (ASL managed: 9.9; private clinics: 1.7; hospital
      trusts: 16.1), average weight (ASL managed: 1.1; private clinics: 0.9; hospital
      trusts: 1.3) and average volume of procedures supplied (ASL managed: 35.000;
      private clinics: 59.000; hospital trusts: 282.000). The administrative SIAS
      database was a useful tool to define indicators aimed at describing
      characteristics of the outpatient care system, although these results must be
      confirmed with a higher and more homogeneous level of coverage.

PMID- 12197049
TI  - [Malignant mesothelioma in Emilia-Romagna: incidence and asbestos exposure].
AB  - This paper describes the activity, the sources of informations, methods and
      results of the "Emilia-Romagna Mesothelioma Registry" (ReM). The Registry started
      in 1996 and collects all cases of Malignant Mesothelioma (MM) occurring in Emilia
      Romagna. 323 new cases (225 males and 98 females) have been detected during the
      period 1996-2001. Most cases (n = 286) concerned pleura. Other observed
      localizations were: peritoneum (n = 30), tunica vaginalis testis (n = 4) and
      pericardium (n = 3). Most of the cases were reported by the Institutes of
      Pathology and Occupational Health and by the Safety Services (respectively the
      62% and the 18%). 87% of all the cases were histologically, 8% TC, 4%
      radiologically and only 1% clinically confirmed. The regional incidence rate (for
      10(5) person-years, age standardized on the 1991 Italian population), has been
      estimated to be 1.98 in males and 0.88 in females. The highest rates were
      registered in Piacenza and Reggio Emilia province among men and Reggio Emilia and
      Ravenna province among women. 72% of cases have been classified as exposed to
      asbestos (64% occupationally and 8% as domestic/environmentally exposed).

PMID- 12197050
TI  - [Malignancies among adolescents and young adults in the province of Trieste,
      Italy, 1972-1993].
AB  - We analysed incidence, survival and mortality from cancer among people aged 15-24
      years resident in the province of Trieste, Italy, during 1972-1993, and evaluated
      the quality of the local diagnostic facilities and of the care provided by local
      hospital departments. We compared the results with those previously published on
      childhood cancer. We recorded 118 new cases of cancer (96% microscopically
      verified) corresponding to a rate, age-standardized to the world population, of
      162.3 (standard error SE = 15.0) per million person-years. The diagnostic group
      with the highest rate was that of carcinomas (54.5; SE = 8.7; 40 cases). The
      diagnosis was reached at hospitals in the province of Trieste for 107 cases, with
      a median time of nine days (25th-75th percentile = 5-23) between admission and
      diagnosis. Among patients with leukaemias, lymphomas and brain tumours, this
      interval was longer than in children affected by the same neoplasms. One girl
      with cancer of the uterine cervix refused all treatment. The therapy of the other
      117 cases were co-ordinated by 29 different departments of hospitals located in
      Trieste for 86 cases, in other Italian hospitals for 26 cases and in European
      hospitals for five cases. On the other hand, out of 123 childhood cancers 107
      were co-ordinated by three departments in Trieste, seven by other Italian
      hospitals and nine by foreign hospitals. The 10-year survival probabilities of
      children with acute lymphoblastic leukaemia and non-Hodgkin lymphomas were higher
      than those of patients aged 15-24 years: 66.7% (SE = 9.1) vs 14.3% (SE = 13.2)
      and 77.8% (SE = 13.9) vs 40.0% (SE = 21.9), respectively.

PMID- 12197051
TI  - [Human papillomavirus: a vaccine against cervical carcinoma uterine].
AB  - Human papillomavirus (HPV) has been identified in fewer than 20 years as the
      central cause of cervical carcinoma and one of the most powerful known human
      carcinogens. At least 20 different types of HPV have been associated with
      relative risks of approximately 100 for both squamous-cell carcinoma and the
      rarer adenocarcinoma of the cervix uteri. Cytologic screening programs have
      contributed to the decline of cervical cancer mortality in Europe and the United
      States. Long-term screening programs remain, however, outside the reach of the
      poorest countries, where 80% of deaths for cervical carcinoma occurs. More than
      20 different types of prophylactic and/or therapeutic vaccines against HPV are
      being evaluated in clinical or preclinical studies. One such type, a prophylactic
      vaccine based on the marked immunogenicity and safety of the empty viral capsid,
      will start being evaluated in 2002 in 3 phase-III randomized studies, mostly in
      the United States and Latin America. The International Agency for Research on
      Cancer and World Health Organization are planning, in parallel with the studies
      above, a double blind randomized phase IV study of approximately 40,000
      adolescent and young women in Asia. Such study, which should include a cluster
      randomization (by village of birth); a comparison with another vaccine (rather
      than with placebo); and, possibly, the inclusion of adolescents and young adults
      of male sex. Such trial may accelerate by many years the availability of an anti
      HPV vaccine among populations at highest risk for cervical carcinoma.

PMID- 12197052
TI  - [PCB contamination: Brescia (Northern Italy) is more polluted than Seveso].

PMID- 12197053
TI  - [Freedom of choice: an unconditional value?].

PMID- 12197054
TI  - [How the protection of health and safety changes in the workplace].

PMID- 12197055
TI  - [Screening mammography: are epidemiology and common sense compatible?].

PMID- 12197056
TI  - [Epidemiology: a discipline for the professional profile of the organization of
      the national health system. The opinion of the Italian Association of
      Epidemiology].

PMID- 12197057
TI  - A failure of public trust.

PMID- 12197058
TI  - Assessment and treatment of scoliosis.

PMID- 12197059
TI  - Key developments in paediatrics.

PMID- 12197060
TI  - Managing ADHD, autistic spectrum and tic disorders.

PMID- 12197061
TI  - Integrating appraisal, revalidation and PDPs.

PMID- 12197062
TI  - Alice Munro's "Fits": secrets, mystery, and marital relations.

PMID- 12197063
TI  - The ghost in the mother: strange attractors and impossible mourning.

PMID- 12197064
TI  - "Every man kills the thing he loves": object-use and potential space in the
      Winter's Tale.

PMID- 12197065
TI  - Aloneness with aesthetic pleasure: a developmental step reflected in memory and
      dream.

PMID- 12197066
TI  - Misreading Cressida.

PMID- 12197067
TI  - Single bead parallel synthesis and screening.
AB  - Microstructured silicon wafers were employed as miniaturized solid-phase reaction
      vessels as well as miniaturized micro titer plates. Employing piezoelectric drop
      on-demand liquid jets, a combinatorial library of 256 Peptides was synthesized on
      single beads. The synthesis protocol was associated to the location in the
      silicon nano-well arrangement. Products were photolytically cleaved in the same
      well that was used for synthesis and subsequently interrogated for thrombin
      inhibition in a homogeneous competition assay. The assay procedure was based on
      drop-on-demand liquid delivery and laser induced fluorescence imaging. The novel
      format proved useful for the integration of both synthesis and screening into one
      platform, a prerequisite for an iterative, evolutionary approach towards drug
      discovery.

PMID- 12197069
TI  - Solid-phase synthesis of tetrahydro-1,4-benzodiazepin-2-one derivatives.
AB  - An efficient method for solid-phase construction of tetrahydro-1,4-benzodiazepin
      2-one scaffold is described. Polymer-bound 4-(bromomethyl)-3-nitrobenzoic acid
      was reacted with alpha-amino acid methyl esters, followed by nitro group
      reduction and hydrolysis. Subsequent intramolecular cyclization and alkylation at
      N(4) afforded the structurally diverse products in high yields and excellent
      purities.

PMID- 12197068
TI  - Identification of peptides that neutralize bacterial endotoxins using beta
      hairpin conformationally restricted libraries.
AB  - Bacterial endotoxins are the major mediator of septic shock; therefore, endotoxin
      neutralizing molecules could have biomedical applications. The septic shock
      cascade relies in a series of molecular recognition processes. The large contact
      surface described for the interacting macromolecules, in most cases, prevents the
      identification of small molecules that could modulate such recognition events.
      Here we report on a beta-hairpin conformationally restricted combinatorial
      library that has been generated and screened towards the identification of new
      peptides that neutralize bacterial endotoxins. Starting with a de novo designed
      linear peptide that shows a beta-hairpin structure population of around 30%,
      (Ramirez-Alvarado, M., Blanco, F. J. and Serrano, L. Nat. Struc. Biol., 7, 604
      612 (1996)), we selected four positions to build up a combinatorial library of
      20(4) sequences. Deconvolution of the library reduced such a sequence complexity
      to 8 defined sequences. The newly identified peptides have a biological activity
      equivalent to that reported for peptides derived from natural endotoxin-binding
      proteins.

PMID- 12197071
TI  - Mining combinatorial data in protein sequences and structures.
AB  - Combinatorial searches of structural and physical chemical properties involving
      the components of libraries of dipeptide, tripeptide and tetra peptide fragments
      were carried out in the Protein Data Bank and the SwissProt databases. The
      properties investigated are structural propensities, co localization of peptide
      fragments in protein sequences, interactions between peptide fragments in close
      structural proximity and the participation of physical chemical profiles in the
      distribution of structural motifs among peptide fragments. The results obtained
      for each combinatorial search in the study are classified according to the
      structural motifs alpha-helix, beta-sheet, reverse turn I and reverse turn II.
      The application of combinatorial data mined in protein databases to the design of
      new peptide libraries is discussed. The present findings have implications for
      the study of protein structure which are also discussed.

PMID- 12197070
TI  - Identification of selective inhibitors of acetylcholinesterase from a
      combinatorial library of 2,5-piperazinediones.
AB  - The potentiation of central cholinergic activity has been proposed as a
      therapeutic approach for improving cognitive function in patients with
      Alzheimer's disease. Increasing the acetylcholine concentration in brain by
      modulating acetylcholinesterase (AChE) activity is among the most promising
      strategies. We have used a combinatorial approach to identify different 2,5
      piperazinediones (DKP) with AChE inhibitory activity. Our goal was to find
      inhibitors exhibiting high AChE/BuChE (butyrylcholinesterase) selectivity, in
      order to reduce the undesirable side effects elicited by most of the inhibitors
      that have been developed to date. Screening of a DKP library constructed on solid
      phase using the multiple parallel synthesis format, resulted in the
      identification of several compounds with moderate efficacy on AChE. In
      particular, DKP-80 had an IC50 = 2.2 microM with no significant inhibitory
      activity on BuChE. Moreover, estimated values of Clog P and log BB for the most
      active compounds fulfilled the bioavailability requirements for enzyme inhibitors
      acting on the central nervous system. In order to understand the inhibitory
      properties of the ligand at the molecular level, molecular dynamics simulations
      were computed on DKP-80 complexed to AChE, and the most relevant binding
      interactions of this inhibitor to the active center of the enzyme were
      characterized. Overall the present results indicate that the DKP-based compounds
      identified are novel AChE inhibitors which may be considered likely lead
      compounds for further development of drug candidates against Alzheimer's disease.

PMID- 12197073
TI  - Solid phase vs. solution phase differential behavior: formation of a salicylate
      structure from a malondialdehyde moiety.
AB  - Treatment of 2, solid supported synthetic equivalent of 3-formylchromone (4), and
      ethyl acetoacetate affords the salicylate structure 8 instead of the previously
      reported isophtalate 7. This is the first formation of a salicylate by a double
      carbonyl condensation of a malondialdehyde moiety ever reported.

PMID- 12197072
TI  - New approach for preparation of 2,3,7-trisubstituted 3,4-dihydroisoquinolinone
      libraries on solid phase.
AB  - In an attempt to prepare 7-substituted 3,4-dihydroisoquinolinone family of
      compounds, we observed an unexpected decarboxylation. The reaction of 4
      nitrohomophthalic anhydride with a Schiff base formed on solid support leads to
      the formation of core structure. LC-MS and 1H NMR analysis confirmed the
      structure of unexpected intermediate. A library of 38,400 compounds was produced
      using this new synthetic approach.

PMID- 12197074
TI  - Multicriteria analysis of environmental quality in Taipei: public preferences and
      improvement strategies.
AB  - The public preferences for environmental quality should be a primary
      consideration of planners and decision-makers in environmental systems planning.
      In the first stage of multicriteria analysis, a multi-attribute evaluation model
      for determining public preferences is formulated. The environmental indices are
      defined for a comparison of environmental quality in different metropolitan
      districts. The public preferences of the environmental quality in Taipei are
      obtained using the weighted average rating method. The results indicate air
      quality and noise pollution as main public concern. In the second stage of
      multicriteria analysis, strategies are proposed to improve the air quality, and
      criteria are established. The experts evaluated all alternative strategies
      according to the criteria. The alternatives are ranked applying the compromise
      ranking method.

PMID- 12197075
TI  - A comparison of different biogeographical classifications of Europe, Great
      Britain and Spain.
AB  - Various biogeographical and bioclimatic classifications of a number of regions,
      countries and continents have been created to meet different objectives. A policy
      maker might ask the question 'why is there no single accepted classification and
      how do the different classifications compare with one another?' In order to
      answer these two questions three classifications created by different methods for
      Great Britain and two for Spain are compared using the Kappa statistic. All of
      the classifications were created from data on cellular grids with a set window
      size. Further non-statistical comparisons are made with other classifications.
      The biogeographic classifications studied in this paper produced three different
      types of zone: those that were always identified whatever the method; those that
      were broadly similar but where the boundaries differed; and those that were
      unique to a particular classification. These different types of zone are likely
      to exist for any comparison between classifications of a particular region. The
      extent of the geographic window from which data were obtained had a major effect
      on the classification of grid cells at the edges of the window. For example, the
      few grid cells in the south of England, with characteristics of continental
      Europe, are not detected if data from Great Britain alone are used for the
      classification. We conclude that the data window should always be larger than the
      area for which the classification is being made. The objective Kappa statistic,
      although useful, was not capable of discerning similarities and dissimilarities
      that appear obvious to the subjective human eye. Although the details of the
      classifications differed there were broad similarities between the
      classifications and these differences reflect important divisions along major
      environmental axes that have been inferred by earlier biogeographers. As the
      divisions are real there is a sound basis for their use in future land use or
      environmental policy.

PMID- 12197076
TI  - Restoring fire as an ecological process in shortgrass prairie ecosystems: initial
      effects of prescribed burning during the dormant and growing seasons.
AB  - Prior to Anglo-European settlement, fire was a major ecological process
      influencing the structure, composition and productivity of shortgrass prairie
      ecosystems on the Great Plains. However during the past 125 years, the frequency
      and extent of grassland fire has dramatically declined as a result of the
      systematic heavy grazing by large herds of domestic cattle and sheep which
      reduced the available levels of fine fuel and organized fire suppression efforts
      that succeeded in altering the natural fire regime. The greatly diminished role
      of recurrent fire in these ecosystems is thought to be responsible for
      ecologically adverse shifts in the composition, structure and diversity of these
      grasslands, leading specifically to the rise of ruderal species and invasion by
      less fire-tolerant species. The purpose of this study was to evaluate the
      ecological effects of fire season and frequency on the shortgrass prairie and to
      determine the means by which prescribed fire can best be restored in this
      ecosystem to provide the greatest benefit for numerous resource values. Plant
      cover, diversity, biomass and nutrient status, litter cover and soil chemistry
      were measured prior to and following fire treatments on a buffalograss-blue grama
      shortgrass prairie in northeastern New Mexico. Dormant-season fire was followed
      by increases in grass cover, forb cover, species richness and concentrations of
      foliar P, K, Ca, Mg and Mn. Growing-season fire produced declines in the cover of
      buffalograss, graminoids and forbs and increases in litter cover and levels of
      foliar P, K, Ca and Mn. Although no changes in soil chemistry were observed, both
      fire treatments caused decreases in herbaceous production, with standing biomass
      resulting from growing-season fire approximately 600 kg/ha and dormant-season
      fire approximately 1200 kg/ha, compared with controls approximately 1800 kg/ha.
      The initial findings of this long-term experiment suggest that dormant-season
      burning may be the preferable method for restoring fire in shortgrass prairie
      ecosystems where fire has been excluded for a prolonged time period.

PMID- 12197077
TI  - The use of choice experiments in the analysis of tourist preferences for
      ecotourism development in Costa Rica.
AB  - Many nations promote nature-based tourism in order to promote the dual goals of
      nature conservation and income generation. To be most effective in providing
      services that facilitate achievement of these goals, decision makers will need to
      understand and incorporate tourist preferences for nature appreciation,
      infrastructure, use restrictions, and other attributes of national parks and
      protected areas. This paper presents the use of choice experiments as a mechanism
      to analyze preferences of national and international tourists in relation to the
      development of Barva Volcano Area in Costa Rica. In this section of the Braulio
      Carrillo National Park, managers are faced with an immediate need to plan for
      greatly increased visitation rates due to a new road, which will greatly improve
      access. Choice sets were developed in collaboration with park managers. A survey
      was conducted of 171 Costa Rican and 271 foreign tourists who visited Poas
      Volcano, a well-visited alternative site to Barva Volcano. Survey data was
      analyzed using conditional multinomial logit models. Results of the study
      demonstrate, that both sets of tourists preferred: (i) improved infrastructure;
      (ii) aerial trams with observation towers and picnic areas; (iii) more
      information; and (iv) low entrance fees. Foreign tourists demonstrated strong
      preferences for the inclusion of restrictions in the access to some trails,
      whereas Costa Ricans did not show any significant preference for restrictions.
      Marginal willingness-to-pay for greater information was estimated to be $1.54 for
      foreign tourists and $1.01 for Costa Rican visitors. The study concludes that
      choice experiments are a useful tool in the analyses of tourist preferences for
      the development of protected areas in developing countries.

PMID- 12197078
TI  - Environmental management of small-scale and artisanal mining: the Portovelo
      Zaruma goldmining area, southern Ecuador.
AB  - This paper considers technical measures and policy initiatives needed to improve
      environmental management in the Portovelo-Zaruma mining district of southern
      Ecuador. In this area, gold is mined by a large number of small-scale and
      artisanal operators, and discharges of cyanide and metal-laden tailings have had
      a severe impact on the shared Ecuadorian-Peruvian Puyango river system. It is
      shown to be technically possible to confine mining waste and tailings at a
      reasonable cost. However, the complex topography of the mining district forces
      tailings management to be communal, where all operators are connected to one
      central tailings impoundment. This, in turn, implies two things: (i) that a large
      number of operators must agree to pool resources to bring such a facility into
      reality; and (ii) that miners must move away from rudimentary operations that
      survive on a day-to-day basis, towards bigger, mechanized and longer-term
      sustainable operations that are based on proven ore reserves. It is deemed
      unlikely that existing environmental regulations and the provision of technical
      solutions will be sufficient to resolve the environmental problems. Important
      impediments relate to the limited financial resources available to each
      individual miner and the problems of pooling these resources, and to the fact
      that the main impacts of pollution are suffered downstream of the mining district
      and, hence, do not affect the miners themselves. Three policy measures are
      therefore suggested. First, the enforcement of existing regulations must be
      improved, and this may be achieved by the strengthening of the central authority
      charged with supervision and control of mining activities. Second, local
      government involvement and local public participation in environmental management
      needs to be promoted. Third, a clear policy should be defined which promotes the
      reorganisation of small operations into larger units that are strong enough to
      sustain rational exploration and environmental obligations. The case study
      suggests that mining policy in lesser-developed countries should develop to
      enable small-scale and artisanal miners to form entities that are of a
      sufficiently large scale to allow adequate and cost-effective environmental
      protection.

PMID- 12197079
TI  - An ecosystem approach to population management of ungulates.
AB  - Harvest objectives for wild ungulates have traditionally been based on population
      models that do not consider ecosystem effects of ungulate herbivory, nor
      interactions between native and domestic ungulate species. There is a need for
      ecosystem models to allow wildlife managers to evaluate potential ecosystem
      effects of management scenarios. The utility of the SAVANNA simulation model for
      estimating elk population objectives within an ecosystem context was demonstrated
      for North Park, Colorado, USA. Effects of different elk population levels were
      evaluated for range condition, elk and cattle forage, elk and cattle condition,
      forage and condition of mule deer and moose, plant production, and plant
      community composition. Analyses were based on 30-year simulation runs using
      variable, historical weather. Another set of analyses utilized stochastic weather
      patterns. For management scenarios using the historical climate pattern,
      increasing elk populations caused biomass reductions of palatable plant species,
      particularly on areas of high winter density, where mean leaf biomass of
      palatable shrubs declined from 26.97 g/m2 at 0 elk to 20.82 g/m2 at 4000 elk
      (3.73 elk/km2), a 23% decline. At population levels of 5000 elk (4.68 elk/km2) or
      greater, elk body condition declined sharply following a severe winter. The
      availability of palatable browse on critical winter range was likely the limiting
      factor. However, when random climate patterns were simulated for the same
      scenarios, the threshold level for density-dependent effects varied with climate,
      ranging from 2000 to 10,000 elk. We suggest that elk population levels from 4000
      to 5000 animals represent a conservative population objective for the North Park
      elk herd. Also, increasing elk population levels appears to intensify
      intraspecific competition among elk, far more than interspecific competition with
      cattle. Resolution of elk-cattle conflicts is likely to be facilitated by
      managing elk distribution, rather than overall elk population levels.

PMID- 12197081
TI  - Habitat suitability modelling for calcareous grassland restoration on the South
      Downs, United Kingdom.
AB  - The South Downs Area of Outstanding Natural Beauty, UK, is an internationally and
      nationally important landscape, which contains a significant proportion (28%) of
      the southeast of England's calcareous grassland resource. The traditional
      calcareous grassland habitats characteristic of the downland landscape have
      suffered significant losses since the Second World War, and the remaining sites
      are small, fragmented and confined to the more marginal areas, often steeper
      slopes. The re-creation and restoration of these species rich grasslands has
      become a central aim of national and regional conservation organisations,
      however, the methods and mechanism by which restoration sites could be identified
      has not been clarified. The purpose of this work was to study the landscape
      characteristics of the calcareous grassland systems, and by use of GIS-based
      modelling approaches identify those sites on the downland most suited to the re
      establishment and expansion of calcareous grasslands. Using a weighted scoring
      approach, a GIS-based Habitat Suitability Model is developed for use as a tool to
      support strategic landscape evaluation and to provide a method of identifying
      sites for targeted restoration. The approach models the relationship between
      specific grassland communities and topographic variables, and is applied to the
      South Downs landscape in order to predict the nature of grassland communities
      likely to result from restoration efforts at specific sites.

PMID- 12197080
TI  - Factors influencing fire behaviour in shrublands of different stand ages and the
      implications for using prescribed burning to reduce wildfire risk.
AB  - Fire behaviour under experimental conditions is described in nine Mediterranean
      gorse shrublands ranging from 3-12 years of age with different fuel loads.
      Significant differences in the fire-line intensity, fuel load and rate of fire
      spread have been found to be related to the stage of development of the
      communities. Fire spread is correlated with fuel moisture using multiple
      regression techniques. Differences in fuel moisture between mature and young
      communities under moderate weather conditions have been found. The lower moisture
      content identified in the mature shrubland is due both to the decreasing moisture
      content of senescent shrubland in some species, mainly in live fractions of Ulex
      parviflorus Pour. fuel, and to a substantial increase in dead fuel fractions with
      low percentages of moisture content. The result is that the older the shrubland
      is, the greater will be the decrease in the total moisture content of the
      vegetation. In these moderate weather conditions, the fire intensity of the
      mature community was as high as the maximum intensity recommended for prescribed
      fires. This fact seems to indicate that, even under moderate conditions,
      prescribed burning as an alternative management tool in the mature shrubland must
      always take into account fuel control; on the other hand, this technique could be
      applied more easily when the shrubland is at an intermediate growth stage (4-5
      years of age). Therefore, more frequent low-intensity prescribed fires are
      indicated to abate the risk of catastrophic fire.

PMID- 12197082
TI  - [Familial combined hyperlipemia in childhood].

PMID- 12197083
TI  - [Compliance with nebulized therapy in childhood].
AB  - While in the past diagnostic and therapeutic means were rather limited, nowadays
      doctors have a vast and valid selection of both at their disposal which, if used
      correctly, are able to successfully treat various pathologies. It is for this
      reason that the paediatrician undertakes to give patients--and above all their
      parents--all the correct information regarding their treatment and/or lifestyle
      in order to obtain the best possible therapeutic results as well as optimum
      health conditions. However, despite efforts on the part of the paediatrician, the
      parents and even the patients themselves, much of what is advised is often partly
      ignored, forgotten or incorrectly implemented, whether intentionally or by
      mistake. In essence, the compliance to advice given is often inadequate
      especially in more serious conditions such as asthma. All of these problems are
      mainly due to the fact that communication is more than often poor, despite the
      primary role it plays in the compliance to treatment and its correct
      implementation. Such impaired communication is usually caused by a sense of
      wanting to do things quickly on the part of the doctor, the patient and/or the
      family. Moreover, it must also be said that nowadays patients above all are
      impatient and the desire to recover is rarely equal to the commitment shown
      towards treatment. All of this obviously has negative affects on our patients'
      health conditions as well as on health care costs. Frequently failures and no
      significant reduction in mortality due to asthma, especially during adolescence
      when interpersonal relationships are more difficult, are a reality. Moreover,
      this reality strongly suggests that, despite doctors' competence and progress in
      both therapy and technology which permit the administration of simple to use
      medicines such as aerosols, greater commitment is required in order to obtain
      better results which are consistent with the current availability of such
      technological and therapeutic measures.

PMID- 12197084
TI  - [Solitary kidney].
AB  - A functionally solitary kidney may be the consequence of renal agenesis,
      dysplasia, or surgical procedures. Compensatory hypertrophy and physiologic
      mechanisms intervene to preserve renal function. The authors discuss the
      physiopathology of solitary kidney in several clinical conditions.

PMID- 12197085
TI  - [Influence of the early renal status on natural history of vesico-ureteral reflux
      diagnosed in the first six month of life].
AB  - INTRODUCTION: Ultrasonographic and radionuclide imaging of kidney in presence of
      major vesicoureteric reflux, diagnosed in the first months of life, reflects a
      congenital anomaly of development of ureteric bud and metanephric blastema, more
      than a parenchymal damage secondary to superimposed infections. These lesions are
      mainly observed in male infants affected by reflux and referred on the basis of a
      prenatal diagnosis. The impact of therapy on these kidneys is still debated.
      PATIENTS AND METHODS: Among 273 pediatric patients with VUR observed between 1991
      and 2000, 48 cases have been selected where a reflux grade III or greater had
      been diagnosed within the first six months of life. Cause of admission was
      prenatal diagnosis in 29 cases and recurrent infection in 19. Reflux was
      bilateral in 30 patients. Cases of VUR associated to other urological or
      neurological anomalies were excluded. A complete ultrasonographic, cystographic
      and radionuclide study was performed in all patients included in the present
      study within the fourth month of life. Mean Follow up lasted 17 months. Renal
      damage was graded by ultrasonography and DMSA renal scan on the basis or of a
      reduction in total kidney size and a poor radionuclide uptake either of an
      altered renal profile associated to focal defects of uptake. RESULTS: Resolution
      of reflux within the mean follow up period, was observed in 16 patients, even
      with high grade VUR, whenever major renal lesions were absent or focal. When
      severe renal damage was initially demonstrated the expectancy of reduction or
      resolution of VUR was significantly reduced and surgical option was considered.
      CONCLUSIONS: Among patients with major VUR diagnosed in the first months of life,
      early renal status affects prognosis more than the severity of reflux.

PMID- 12197086
TI  - [Retrospective analysis of Henoch-Schonlein purpura in children: diagnostic
      difficulties and renal outcome].
AB  - OBJECTIVE: To assess clinical presentation, diagnostic difficulties, natural
      history and prognostic indicators of renal involvement of Henoch Schonlein
      Purpura, a ten-years retrospective analysis of all patients case records was
      performed. METHODS: After a variable interval of 1 to 10 years following the
      vasculitic episode all the children came to the outpatient clinic for history
      taking, clinical examination, blood pressure measurements, urine analysis and
      renal function assessment. RESULTS: 54 children, mean age 5.9 +/- 2.5, were
      identified. The purpuric rash was associated with arthritis in 46 patients (85%),
      abdominal pain in 28 (51.8%), temperature > 38 degrees C in 11 (20%). The
      purpuric rash was present at on presentation in 39 subjects (72%) whereas in 15
      children (28%) it followed the subsequent signs or symptoms that were arthritis
      in 8 (53.3%), joint pain in 2 (13.3%), abdominal pain in 5 (30.3%). Abdominal
      pain was the only symptom of presentation in 5 patients; two of them underwent
      surgical laparotomy.

PMID- 12197087
TI  - [One stop surgery in pediatric surgery. Preliminary report].
AB  - The One-Stop Surgery (OSS) is a new method of Day Surgery, which combines
      preoperative evaluation and subsequent operation into one visit. This report
      describes the initial experience of the authors. Referring physicians were
      informed by fax about method and selected surgical procedures. Included form
      helped them to gain anamnestic data and to inform parents about preoperative
      fast. Form was then sent back by fax to the pediatric surgeon and
      anesthesiologist who determined the patient suitability and scheduled the day of
      the surgery. At hospital admission, if the diagnosis was confirmed and no
      anesthesiologic contraindications were discovered, the patient underwent the
      prescheduled surgical procedure and was discharged as a day case. Another form
      containing informations about home postoperative care and telephone numbers for
      emergency call was gave to the parents. From November 2000 through February 2001
      43 patients, aged from 2 to 7 years, underwent one-stop surgical procedure:
      central venous catheter removal (n = 16), umbilical (n = 2) and inguinal (n = 10)
      hernia repair, prepuce dorsal slit (n = 15). Recovery of all patient was
      uneventful. None of them called during the period considered necessary for
      postoperative follow-up. Decreased costs and increased satisfaction of the
      patients and parents are the most important advantages of the OSS. Potential
      disadvantages are a not appropriate indication for the planned procedure and/or
      an anesthesiologic contraindication at hospital admission. It could involve a
      waste of human and financial resources and an useless psychologic stress for the
      family. Authors conclude it is not advisable the OSS use on a large scale without
      a sound experience in pediatric Day Surgery.

PMID- 12197088
TI  - [Varicocele at a prepubertal age. Adolescent varicocele].
AB  - Varicocele is a dilatation of the spermatic veins, particularly on the left side,
      and represents one of the most frequent causes of male infertility. Its frequency
      in pre-adolescence varies from 10% to 15%. Even today varicocele pathogenesis is
      not clear. In the period from August 1990 to August 1999, 35 males between 10 and
      16 years of age were treated surgically in our Institution via interruption of
      the internal spermatic vein using Palomo's technique. Patients that reached the
      age of 18 after surgery have had a spermiogramm. The problem of varicocele
      therapy in pre-adolescence has not yet been resolved with regard to surgical
      therapy and follow-up.

PMID- 12197089
TI  - Bronchoscopy in newborns with esophageal atresia.
AB  - The aim was to evaluate the influence of rigid laryngotracheo-bronchoscopy in
      newborns with oesophageal atresia (OA) and tracheoesophageal fistula (TOF) in
      preventing complications, improving diagnosis and surgical treatment. Among 76
      consecutive newborns, received in the Paediatric Intensive Care Unit (PICU) from
      January 1990 to September 2001 with prenatal o perinatal suspected OA, forty-five
      had one or more other congenital anomalies. They were divided in I Montreal's
      risk group for 73.7% (56) and in the II one for 26.3% (20). Endoscopic procedure
      was performed in the operating room with Storz's rigid ventilating bronchoscope
      just before surgery, in all babies. With bronchoscopic examination we were able
      to identify the level, number and size of TOF and to visualise anatomical
      variants in 76 children. 15 children with OA had a gasless abdomen, but an upper
      pouch fistula was found only in three cases. In another four cases bronchoscopy
      confirmed the diagnosis of an "H" fistula and cervical surgical approach was
      established. One case had only oesophageal stenosis. 56 patients had fistula in
      lower pouch and in the last 38 cases we proceeded with selective transtracheal
      fistula incannulation and then we provided gastric drainage. One quadriforcation,
      2 triforcations, 3 aberrant right upper lobe bronchi, 1 congential subglottic
      stenosis and 1 associated with a congenital subglottic stenosis and 1 left main
      bronchus agenesia were detected. No complications were correlated to the
      procedure and no babies had early pneumonia. Continuous feeding was achieved in
      70 out of 76 patients: 46 primary anastomosis with 12 staged repairs (OA I and II
      type long gap), 4 resections of TEF, 8 oesophagocoloplasty. Nine babies (11.8%)
      did not survive. Clinical follow-up was possible in all the survivors. Mortality
      rate in the high-risk patients with OA remains high because of the many
      complications that may occur. Tracheal endoscopy is useful in improving the
      diagnostic approach and to prevent pulmonary complications. Fistula incannulation
      minimizes the risk of gastric distension and its detrimental effect on
      ventilation, helping the surgeon to identify TEF easily and quickly. Moreover,
      the endoscopic approach offers obvious advantages for the anaesthesiologist and
      the surgeon and has proven, in our experience, to be effective.

PMID- 12197090
TI  - [Chronic idiopathic gastric volvulus in children].
AB  - OBJECTIVE: We report clinical, radiograpic and instrumental data about 18 cases
      of gastric chronic idiopathic volvulus observed since 1997 to june 2000. METHOD:
      All cases diagnosed by barium meal, performed for vomiting or after a pHmetric
      esophageal monitoring, in cases of atipical symptoms of gastroesophageal reflux
      disease. RESULTS: All patients underwent a conservative treatment (antireflux
      position and procinectics): 5 recovered after 1 year of treatment and 13 were
      operated on because they did not improve during medical therapy or relapsed after
      the end of conservative treatment. CONCLUSION: Abnormal position of the stomach
      is not an absolute indication for surgical treatment. When medical treatment does
      not obtain improvement in symptoms, surgical option has to be discussed.

PMID- 12197091
TI  - [Familial transient red cell aplasia from parvovirus B-19 infection].
AB  - In our Paediatric Clinic we observed a case of transient aplastic crisis caused
      by Parvovirus B19 in a child and his mother, both affected by spherocytic
      haemolytic anemia. Anti-Parvovirus IgM antibody titre and viral search by PCR
      were positive. Anemia was treated with transfusion of concentrated red blood
      cells. In case of a family onset of hyperacute anemia it is necessary to consider
      a bone marrow aplastic crisis of the red series, induced by Parvovirus B19,
      especially if there is notice of an ongoing outbreak of erythema infectiosum.

PMID- 12197092
TI  - [Jacopo's chest (bad history of a pleural empyema). A case report].
AB  - We present a case of pleural empyema, occurred in a healty 7 years boy. He was
      admitted to our hospital because of a lobare pneumonitis. The patient was
      administered with a 2 degrees generation Cefalosporine given intramuscularly and
      with Corticosteroid (1 mg/kg/die). After an initial improvement of his clinical
      conditions, he got worse so that he underwent a TC scan which showed the presence
      of a left pleural empyema requiring the insertion of an intercostal tube drainage
      followed by an intervention of decortication. The boy had some evidence of a
      staphylococcal etiology such as the evolution in empyema itself, the augmentation
      of antistafilolisinic title found during the illness, and the typical finding of
      blebs on chest radiograph. As cultures from both blood and drainage liquid
      samples remained sterile, we were unable to demonstrate a clear bacterial
      etiology of the empyema. It remains doubtful if corticosteroid administration
      could contribute to the severity of the pneumonia evolution.

PMID- 12197093
TI  - [Torsion of a wandering spleen: ultrasonography and computer tomography in
      conservative treatment. A case report].
AB  - Torsion of the vascular pedicle in a wandering spleen is treated conservatively
      in most of the cases whenever irreversible necrosis of the organ is not occurred.
      A case, in a 10 years old boy, is reported. The patient was admitted for acute
      abdominal pain and was investigated by ultrasounds, which showed an ectopic
      enlarged spleen at the left flank, without any sign of parenchymal necrosis. A
      spiral contrast enhanced angio-CT scan confirmed the diagnosis and demonstrated
      multiple ischemic lesions of splenic pulp mainly at the lower pole. The child was
      treated with splenopexy followed by un uneventful recovery. CT scan study in
      cases of torsion of a wandering spleen is of great help in confirming clinical
      and ultrasonographic diagnosis and in demonstrating the amount of ischemic lesion
      of the organ before surgical exploration.

PMID- 12197094
TI  - [Urologic malformation and renal dysplasia: new knowledge].

PMID- 12197096
TI  - After the fall. New thinking to make skyscrapers safer.

PMID- 12197097
TI  - Defense tech. Training for terror.

PMID- 12197095
TI  - Unsettled air. The unknown health effects of the towers' collapse.

PMID- 12197099
TI  - Real time.

PMID- 12197098
TI  - Biotech. The terminator's back.

PMID- 12197100
TI  - That mysterious flow.

PMID- 12197102
TI  - How to build a time machine.

PMID- 12197101
TI  - A hole at the heart of physics.

PMID- 12197103
TI  - Times of our lives.

PMID- 12197104
TI  - Remembering when.

PMID- 12197105
TI  - Clocking cultures.

PMID- 12197106
TI  - A chronicle of timekeeping.

PMID- 12197107
TI  - Ultimate clocks.

PMID- 12197108
TI  - Epizootiology of Syphacia obvelata from a domestic mouse population on the
      subantarctic Kerguelen Archipelago.
AB  - The effects of abundance, age, and sex of feral domestic mice Mus musculus
      domesticus on infections with the nematode parasite Syphacia obvelata were
      analyzed during a long-term study of the mouse population on Guillou Island (1.45
      km2), a part of the subantarctic Kerguelen Archipelago. The population dynamics
      of the nematode did not follow the variation in host abundance. However,
      depending on the year, differences in pinworm abundance were found between the
      age classes and sex. Such patterns suggest that parasitic infections may have
      been modulated by host-intrinsic factors, e.g., either by the way of innate or
      adaptive immunity, rather than extrinsic factors, e.g., host abundance.

PMID- 12197109
TI  - Can helminth community patterns be amplified when transferred by predation from
      intermediate to definitive hosts?
AB  - Helminth communities in definitive hosts are formed by the acquisition of packets
      of larvae arriving each time an intermediate host is consumed. It is thus
      possible that associations between parasite species or other aspects of community
      structure get transferred from intermediate to definitive hosts. Earlier computer
      simulations showed that associations between 2 parasite species, in particular
      positive associations, could be transferred up the food chain. Here, we alter
      some of the assumptions of previous models and generate new simulations of
      several ways in which source infracommunities in intermediate hosts can be
      transferred to target infracommunities in definitive hosts. In particular, we
      introduced nonrandom selection of intermediate hosts by predatory definitive
      hosts, to mimic the phenomenon of host manipulation by parasites; this consisted
      in biasing predation toward intermediate hosts harboring a certain parasite
      species. Overall, our results show that positive covariances between 2 parasite
      species can not only be transferred but can also be amplified during transmission
      to definitive hosts; significant covariance between parasite species can even
      appear in the definitive hosts when none existed in the intermediate hosts.
      Negative covariance was not as readily transferred to definitive hosts and
      amplified, in part because of properties of the presence-absence covariance
      index. Amplification of covariance results from intermediate host manipulation as
      well as from other processes taking place during transmission. These results
      suggest that the patterns of association between helminth species in definitive
      hosts cannot be taken to reflect the processes acting inside those hosts: they
      may simply be inherited, with amplification, from intermediate hosts.

PMID- 12197110
TI  - First record of Neoergasilus japonicus (Poecilostomatoida: Ergasilidae), a
      parasitic copepod new to the Laurentian Great Lakes.
AB  - The parasitic copepod Neoergasilus japonicus, native to eastern Asia, was first
      collected from 4 species of fish (fathead minnow, Pimephales promelas; largemouth
      bass, Micropterus salmoides; pumpkinseed sunfish, Lepomis gibbosus; and yellow
      perch, Perca flavescens) in July 1994 in Saginaw Bay, Lake Huron, Michigan.
      Further sampling in the bay in 2001 revealed infections on 7 additional species
      (bluegill, Lepomis macrochirus; carp, Cyprinus carpio; channel catfish, Ictalurus
      punctatus; goldfish, Carassius auratus; green sunfish, Lepomis cyanellus; rock
      bass, Ambloplites rupestris; and smallmouth bass, Micropterus dolomieu). An
      additional 21 species examined in 2001 were devoid of the parasite. A limited
      collection of fish from Lake Superior (n = 8) and Lake Michigan (n = 46) in 1994
      showed no infection. Neoergasilus japonicus is most frequently found attached to
      the dorsal fin and, in decreasing frequency, on the anal, tail, pelvic, and
      pectoral fins. Prevalence generally ranged from 15 to 70 and intensity from 1 to
      10. The greatest number of copepods on a single host was 44. The copepod
      Neoergasilus japonicus appears to disperse over long distances rather quickly,
      spreading across Europe in 20 yr and then moving on to North America over a span
      of 10 yr. Its main vehicle of transport and introduction into the Great Lakes is
      probably exotic fish hosts associated with the fish-culture industry.

PMID- 12197111
TI  - Immuno-electron microscopic observation of Plasmodium berghei CTRP localization
      in the midgut of the vector mosquito Anopheles stephensi.
AB  - The subcellular localization of Plasmodium berghei circumsporozoite protein and
      thrombospondin-related adhesive protein (PbCTRP) in the invasive stage ookinete
      of P. berghei was studied in the midgut of Anopheles stephensi by immuno-electron
      microscopic observations using polyclonal antibodies and immuno-gold labeling.
      PbCTRP was found to be associated with the micronemes of a mature ookinete
      throughout the movement from the endoperitrophic space to the basal lamina of the
      midgut epithelium. PbCTRP was also observed in the electron-dense area outside
      the ookinete, which might have been secreted from the apical pore. PbCTRP is
      found most abundantly at the site of contact between the apical end of an
      ookinete and the basal lamina of an epithelial cell. These results suggest that
      PbCTRP functions as an adhesion molecule for ookinete movement into the midgut
      lumen and epithelial cell and for ookinete association with the midgut basal
      lamina and transformation into an oocyst.

PMID- 12197112
TI  - Investigation of diversity and isotypes of the beta-tubulin cDNA in several small
      strongyle (Cyathostominae) species.
AB  - The diversity of the beta-tubulin cDNAs of the cyathostominae and the occurrence
      of further isotypes were examined in adult worms isolated from an anthelmintic
      naive horse. cDNAs encoding beta-tubulin from Cyathostomum catinatum,
      Cylicocyclus nassatus, Cylicocyclus insigne, Cylicocyclus radiatus, Cylicocyclus
      elongatus, Cyathostomum coronatum, and Cyathostomum pateratum were characterized
      using specific primers developed from the cDNA sequence of Cc. nassatus. The cDNA
      sequences span 1,429 bp and show identities ranging from 95.6 to 100%. The
      deduced protein sequences span 448 amino acids and were 98-100% identical. The
      amino acid sequences of the 7 species varied within and between species at 10
      positions. A 3' Rapid Amplification of cDNA ends using a degenerate forward
      primer was carried out with cDNA from Cy. pateratum, Cy. coronatum, Cy.
      catinatum, and Cc. nassatus to investigate the occurrence of further beta-tubulin
      isotypes. The expected polymerase chain reaction (PCR) product of 400 bp,
      including 306 bp of coding sequence, was amplified, as was an additional fragment
      of 600 nucleotides in the case of Cy. pateratum, Cy. coronatum, and Cy.
      catinatum. Sequencing of the PCR products revealed no evidence for the existence
      of a second beta-tubulin isotype in cyathostomes. The variation in size was
      caused by a length polymorphism within the 3' untranslated region, and 2
      functional mRNAs seem to be transcribed from the same gene.

PMID- 12197113
TI  - One season of pasture exposure fails to induce a protective resistance to
      cyathostomes but increases numbers of hypobiotic third-stage larvae.
AB  - The development of acquired resistance to cyathostome challenge after 1 season's
      exposure to a cyathostome-contaminated pasture was investigated using 17 parasite
      naive ponies, which were 2-3 yr of age. These were divided into 3 groups: 1 to
      graze a cyathostome-contaminated pasture for 4 mo (exposed ponies), 1 to graze a
      "clean" pasture not previously grazed by parasitized animals (nonexposed ponies),
      and 1 group to remain in the barn under helminth-free conditions (parasite-free
      ponies). After pasture exposure all ponies were housed in stalls in the barn
      dewormed with ivermectin (200 micrograms/kg) and oxibendazole (100 mg/kg), a
      treatment that eliminated most cyathostomes encysted in the mucosa as well as all
      luminal parasites, on the basis of necropsies of 5 animals, after 17 days.
      Remaining ponies were challenged with 100,000 cyathostome-infective third-stage
      larvae (L3) per os 3 wk after anthelmintic treatment. Necropsies were performed 7
      wk after the challenge. Total cyathostome burdens (luminal plus encysted stages)
      were not significantly different among any of the groups. However, a
      significantly higher percentage of hypobiotic early L3 (EL3) and a lower
      percentage of adults were found in exposed ponies. This observation supports the
      hypothesis that resistance acquired through exposure promotes cyathostome
      hypobiosis. This increase in EL3 in exposed ponies was associated with a
      significant increase in weight of cecum and ventral colon biopsies.

PMID- 12197114
TI  - Effect of vaccinations with recombinant fusion proteins on Ancylostoma caninum
      habitat selection in the canine intestine.
AB  - Laboratory dogs were vaccinated subcutaneously with 3 different recombinant
      fusion proteins, each precipitated with alum or calcium phosphate. The vaccinated
      dogs were then challenged orally with 400 third-stage infective larvae (L3) of
      the canine hookworm, Ancylostoma caninum. The 3 A. caninum antigens selected were
      Ac-TMP, an adult-specific secreted tissue inhibitor of metalloproteases; Ac-AP,
      an adult-specific secreted factor Xa serine protease inhibitor anticoagulant; and
      Ac-ARR-1, a cathepsin D-like aspartic protease. Each of the 3 groups comprised 6
      male beagles (8 +/- 1 wk of age). A fourth group comprised control dogs injected
      with alum. All of the dogs vaccinated with Ac-TMP or Ac-APR-1 exhibited a
      vigorous antigen-specific antibody response, whereas only a single dog vaccinated
      with Ac-AP developed an antibody response. Dogs with circulating antibody
      responses exhibited 4.5-18% reduction in the numbers of adult hookworms recovered
      from the small intestines at necropsy, relative to alum-injected dogs. In
      contrast, there was a concomitant increase in the number of adult hookworms
      recovered from the colon. The increase in colonic hookworms was as high as 500%,
      relative to alum-injected dogs. Female adult hookworms were more likely to
      migrate into the colon than were males. Anti-enzyme and anti-enzyme inhibitor
      antibodies correlated with an alteration in adult hookworm habitat selection in
      the canine gastroinntestinal tract.

PMID- 12197115
TI  - Characterization of an outbred pregnant mouse model of Neospora caninum
      infection.
AB  - Fetal loss and vertical transmission of Neospora caninum were evaluated in
      outbred Quackenbush (Qs) mice with respect to dose of parasites, N. caninum
      isolate, and route of injection. Mice were infected with NC-Liverpool or NC-SweB1
      at day 5 or 8 of pregnancy with doses of 10(4), 10(6), or 10(7) parasites,
      through either a subcutaneous or intraperitoneal injection. Polymerase chain
      reaction was used to detect N. caninum in the brains of offspring, and enzyme
      linked immunosorbent assay was used to analyze the maternal immune response.
      Vertical transmission occurred in mice given 10(6) NC-Liverpool at day 5 during
      gestation, and a significant (P < 0.05) maternal antibody response was observed
      in mice infected with NC-Liverpool or NC-SweB1 at days 5 and 8 of gestation. This
      study shows that outbred Qs mice are a useful model for the study of vertical
      transmission associated with N. caninum, as they display less clinical disease
      and pathogenesis than inbred mice and have large litters, which is advantageous
      when studying maternal transmission.

PMID- 12197116
TI  - Antigenic significance of a Trypanosoma rangeli sialidase.
AB  - The Trypanosoma rangeli-secreted sialidase was purified by bovine submaxillary
      gland mucin-sepharose affinity chromatography. In immunoblotting analysis,
      antibodies raised against this molecule recognized polypeptides of 73 kDa in T.
      rangeli medium supernatant (TrSialr) and of 70 kDa in the cell lysates of T.
      rangeli (TrSials) and T. cruzi (TcSialL) epimastigotes. TrSialr, TrSials, and
      TcSialL were subjected to proteolytic cleavage with papain; the resultant peptide
      pattern displayed differences in the immunoblotting profiles. TrSials was
      purified by immunoprecipitation, and this protein band was recognized by sera
      from T. cruzi-infected chronic mice and Chagas' disease patients. In contrast,
      TrSialr was not recognized by these sera. The antibodies from the infected mice
      also recognized a band of 70 kDa present in the medium. These preliminary
      observations imply that the released and somatic sialidases are partially
      different molecules, with probably different biological roles. The related
      proteins recognized in T. rangeli and T. cruzi epimastigotes share many antigenic
      characteristics but have some structural differences, probably related to their
      function in the parasitic cell. On the basis of the strong antigenicity of
      TrSials, this molecule is proposed as the antigen for the detection of antibodies
      arising during T. cruzi infection.

PMID- 12197117
TI  - Superoxide anion in Anopheles albimanus hemolymph and midgut is toxic to
      Plasmodium berghei ookinetes.
AB  - The mechanisms of Plasmodium spp. elimination in resistant mosquitoes are not
      completely understood. Some resistant anopheline strains are able to melanize
      Plasmodium spp. ookinetes in their midguts. Because quinoid compounds are potent
      catalysts for free radical generation and because these radicals can be generated
      in association with melanogenesis, it is probable that they play an important
      role in the elimination of parasites. The production of the superoxide anion (O
      2) in the hemolymph and midgut of Anopheles albimanus female mosquitoes and its
      cytotoxic effect on Plasmodium berghei ookinetes were analyzed. Ookinetes
      inoculated into the hemocoel of A. albimanus were covered with melanin and then
      encapsulated by hemocytes within 1 hr. The presence of O-2 in midguts and in
      hemolymph obtained by perfusion was verified by the reduction of 3-(4,5
      dimethylthiazolil-2)-2,5-diphenyl tetrazolium bromide. O-2 was generated in the
      hemolymph obtained by perfusion and midguts only in the presence of
      dihydroxyphenylalanine (L-DOPA), and this reaction was inhibited by superoxide
      dismutase (SOD). Plasmodium berghei ookinetes exposed to hemolymph plus L-DOPA
      were killed in vitro, but addition of SOD prevented their killing.
      Prophenoloxidase transcripts were not observed in midgut epithelium, suggesting
      that toxic compounds may be imported from the hemolymph. These results suggest
      that A. albimanus hemolymph and midguts produce O-2 that may limit Plasmodium
      spp. parasite development.

PMID- 12197118
TI  - The effect of aggregative overwintering on an insect sexually transmitted
      parasite system.
AB  - In contrast to the extensively studied sexually transmitted diseases (STDs) of
      humans, little is known of the ecology or evolutionary biology of sexually
      transmitted parasites in natural systems. This study of a sexually transmitted
      parasite on an insect host augments our understanding of both the parasite's
      population dynamics and virulence effects. The impact of overwintering was
      assessed on the prevalence of the parasitic mite Coccipolipus hippodamiae on the
      two-spot ladybird, Adalia bipunctata. First, the effect of infection on host
      survival was examined during the stressful overwintering period. Box experiments
      in the field revealed that the infected ladybirds, especially males, are less
      likely to survive overwintering. The study provides the first evidence that the
      parasite harms males and suggests revisions of theories on the adaptive virulence
      of sexually transmitted parasites. It also indicates the importance of using a
      range of experimental conditions because virulence can be dependent on host
      condition and sex. Box experiments were also used to examine whether transmission
      of the parasite occurs within overwintering aggregations. These revealed that
      substantial transmission does not occur in aggregations and that transmission is
      predominantly sexual. Overall, the virulence effects and the lack of transmission
      mean that the overwintering period acts to diminish parasite prevalence and will
      retard the spring epidemic associated with host reproductive activity.

PMID- 12197119
TI  - Tachyzoite-induced life cycle of Toxoplasma gondii in cats.
AB  - The tachyzoite-induced cycle of Toxoplasma gondii was studied in 46 cats.
      Tachyzoites of the M-7741 or Me-49 strain of T. gondii were administered orally
      to cats by pouring into the mouth or by stomach tube, or by intraintestinal
      inoculation. Ten weaned cats that had been inoculated with tachyzoites directly
      in the intestine were killed 1, 3, 6, 9, 12, 15, 18, or 25 days later, and their
      tissues were studied histologically and bioassayed in mice. Toxoplasma gondii was
      demonstrable in the blood of 8 cats and in other tissues of all these 10. Four
      out of five 1- to 8-day-old cats fed tachyzoites by stomach tube became infected
      with T. gondii, and 1 became ill because of toxoplasmosis. All 19 weaned cats fed
      tachyzoites (poured into the mouth) became infected, and 6 died of acute
      toxoplasmosis 9-15 days after being fed T. gondii. Six out of 12 weaned cats fed
      tachyzoites by stomach tube became infected but were asymptomatic. Overall, 12
      out of 26 cats observed for 19 days or more shed oocysts with a prepatent period
      (pp) of 19 days or more, with the sole exception of 1 cat that shed oocysts with
      a pp of 5 days. Enteroepithelial stages of T. gondii were not found in any cat
      before oocysts were shed. Cats shed up to 360 million oocysts in a day, and
      oocysts were shed for 4-6 days.

PMID- 12197120
TI  - Effects of freeze-thaw events on the viability of Cryptosporidium parvum oocysts
      in soil.
AB  - The effects of freeze-thaw events on the inactivation of Cryptosporidium parvum
      oocysts in soil were examined. Oocysts were inoculated into distilled water in
      microcentrifuge tubes or into chambers containing soil the water content of which
      was maintained at 3%, 43%, or 78% of the container capacity. The chambers and
      tubes were then embedded in 3 soil samples from different aspects of a hillside
      landscape (Experiments 1 and 2) and in 3 distinct soil types (Experiment 3) and
      frozen at -10 C. Containers were thawed every 3 days for a period of 24 hr in 1-9
      freeze-thaw cycles over 27 days (Experiments 1 and 2) and 2-5 freeze-thaw cycles
      over 15 days (Experiment 3). Oocyst viability was measured using the fluorescent
      dyes 4'6-diaminidino-2-phenylindole and propidium iodide. Inactivation rates were
      greater in soils than in water and greater in dry soil than in moist and wet
      soils. Soil type showed no effect on inactivation. Oocysts subjected to freeze
      thaw cycles had inactivation rates not significantly different from those of
      oocysts subjected to -10 C under static conditions. The results indicated that
      99% of oocysts exposed to soils that are frozen at -10 C will become inactivated
      within 50 days whether or not freeze-thaw cycles occur.

PMID- 12197122
TI  - Component community of larval trematodes in the mudsnail Hydrobia ventrosa:
      temporal variations in prevalence in relation to host life history.
AB  - Temporal variations in the prevalence of larval trematodes in the short-lived
      prosobranch mudsnail Hydrobia ventrosa (Montagu) were investigated in relation to
      host life history and season for 4 successive years in temperate windflats of the
      southern Baltic Sea. The component community of trematode larvae in H. ventrosa
      comprises at least 10 species; families (and species) represented include
      Notocotylidae (1), Echinostomatidae (1 or 2), Heterophyidae (2), Monorchidae (1),
      Microphallidae (3 or 4), Psilostomatidae (1), and Hemiuridae (1). The notocotylid
      Paramonostomum alveatum was the most prevalent species, followed by the
      microphallids Maritrema subdolum and Microphallus sp. Trematode prevalence in H.
      ventrosa fluctuated seasonally. Prevalence usually peaked in summer between July
      and September-October and decreased in late winter-early spring. This seasonal
      change is chiefly explained by the life history patterns of the semelparous snail
      host. Hydrobia ventrosa has a maximum life span of about 2 yr and reproduces
      between June and November of its second calendar year. The first trematode
      infections appeared annually in May when the most abundant cohort of H. ventrosa,
      the second-calendar-year snails, mature. The prevalence continued to increase
      until August-September, throughout the reproductive period of the second-calendar
      year snails, Prevalence decreased during winter, when most of the second-calendar
      year snails died after reproduction. On the basis of longterm laboratory
      experiments, it has been shown that the late autumn-winter mortality was not the
      result of trematode infections. Seasonal patterns of prevalence were similar
      among the trematode species except for the monorchid Asymphylodora demeli, the
      only one using fish definitive hosts. Species-specific differences in the
      seasonal occurrence of prepatent infections and the predominance of certain
      larval stages in winter are interpreted as different strategies of the trematode
      species to survive the harsh winter conditions, or to survive the death of the
      first intermediate host in autumn-winter, or both.

PMID- 12197121
TI  - Reproducible infection of intact Aotus lemurinus griseimembra monkeys by
      Plasmodium falciparum sporozoite inoculation.
AB  - Aotus lemurinus griseimembra is considered one of the best nonhuman primate
      species for malarial studies because of its susceptibility to infection by
      Plasmodium falciparum asexual blood stages. However, reproducible transmission of
      infective P. falciparum sporozoites by mosquito inoculation has been difficult to
      achieve even in splenectomized monkeys. Characterization of an Aotus-P.
      falciparum cyclical transmission model has become a top priority as a result of
      the significant progress toward the development of preerythrocytic malaria
      vaccines. Herein, we describe a reproducible model developed using intact A.
      lemurinus griseimembra monkeys intravenously inoculated with sporozoites from a
      monkey-adapted P. falciparum (Santa Lucia) strain and a wild Falciparum-Cali
      Colombia-4 (FCC-4) strain. Sporozoites were obtained by salivary gland dissection
      of laboratory-reared Anopheles albimanus mosquitoes. Parasitemia was monitored by
      thick-smear microscopy, parasite lactate dehydrogenase (pLDH) determination, and
      mosquito xenodiagnosis. The last method proved to be the most sensitive method
      for monitoring parasitemias. Infection with the Santa Lucia strain showed a mean
      prepatent period of 16 days (range 6-21 days), whereas infection with the wild
      FCC-4 strain resulted in a 24-day prepatent period. Mean peak parasite density
      was approximately 900 parasites/microliter for both parasite strains. The
      prepatent period, the peak of parasitemia, and the duration of patency were
      independent of the size of the sporozoite inoculum and the presence of spleen in
      the host. This model is being successfully used to test the protective efficacy
      of P. falciparum preerythrocytic vaccine candidates.

PMID- 12197123
TI  - Response of intestinal epithelial cells to Trichuris suis excretory-secretory
      products and the influence on Campylobacter jejuni invasion under in vitro
      conditions.
AB  - We previously developed a swine animal model in which natural host resistance to
      Campylobacter jejuni is altered by experimental infection with low numbers of the
      nematode Trichuris suis. Pigs naturally colonized with C. jejuni experience
      colitis because of the invasion of the bacterium approximately 21 days after
      exposure to T. suis. To better understand the mechanism of T. suis-dependent C.
      jejuni colitis, we evaluated the effects of T. suis excretory-secretory products
      (ESPs) on intestinal epithelial cells (IECs) and the influence of ESP on C.
      jejuni invasion in IECs under in vitro conditions. Viability assays revealed a
      dose-dependent cytotoxic response in ESP-treated IECs, particularly IPEC-1 and
      INT407 cells. Transepithelial electrical resistance dropped significantly in IPEC
      1 cells treated on apical and basolateral surfaces, but not in those treated only
      on apical surfaces. Using the gentamicin-killing assay, reduced numbers of
      intracellular C. jejuni were recovered from IECs treated with ESP at 1 mg
      protein/ml concentration. This observation can be at least partially explained by
      a novel antibacterial activity in ESP. Contrary to our hypothesis, ESP at
      subtoxic concentrations did not enhance invasion. In addition to mechanical
      damage from worms, these results suggest that soluble products released by T.
      suis contribute to IEC damage at the site of worm attachment.

PMID- 12197124
TI  - Rhabdochona guerreroensis n. sp. (Nematoda: Rhabdochonidae) from the intestine of
      the gobiid Sicydium multipunctatum from fresh waters in Mexico.
AB  - Rhabdochona guerreroensis n. sp. is described on the basis of specimens recovered
      from the intestine of Sicydium multipunctatum (Regan) (Gobiidae, Perciformes)
      from 2 localities in Mexico. This species is characterized by 12 teeth in the
      prostom (occasionally 11), asymmetrical numbers of postanal papillae, a broad
      distal tip of the larger (left) spicule with a small bifurcation covered by
      narrow cuticular membrane, a smaller (right) spicule with a dorsal barb on its
      distal tip, and filamented eggs.

PMID- 12197125
TI  - Clitellocephalus americanus n. gen., n. sp. (Apicomplexa: Eugregarinida:
      Gregarinidae) from Cratacanthus dubius (Coleoptera: Carabidae: Harpalinae) in the
      Nebraska sandhills and Clitellocephalus ophoni n. comb. (Apicomplexa:
      Eugregarinida: Gregarinidae) from Ophonus pubescens (Coleoptera: Carabidae:
      Harpalinae) in Sete, France.
AB  - Clitellocephalus americanus n. gen., n. sp. (Apicomplexa: Eugregarinida:
      Gregarinidae) is described from Cratacanthus dubius (Coleoptera: Carabidae)
      collected from Keith County in the Sandhills of western Nebraska.
      Clitellocephalus ophoni n. comb. is redescribed using original type material from
      Ophonus pubescens (Coleoptera: Carabidae) collected in Sete, France.
      Clitellocephalus n. gen. is distinguished by a deltoid epimerite with an internal
      anterior obconoid structure and a basal toroidal vacuole, which is retained in
      gamonts. Protomerites are broadly elliptical to cylindrical; deutomerites are
      narrowly obovate. Association is precocious, caudofrontal, and biassociative,
      with the satellite protomerite engulfing the posterior end of the primite
      deutomerite to form an interlock. Gametocysts are spherical. Sporoducts are
      present but reduced and irregular in number. Oocysts are dolioform, dehiscing in
      chains. The species described herein are differentiated by their overall size and
      relative proportion of cellular structures.

PMID- 12197127
TI  - Procamallanus (Spirocamallanus) chetumalensis n. sp. (Nematoda: Camallanidae)
      from the Mayan sea catfish, Ariopsis assimilis, off the Caribbean coast of
      Mexico.
AB  - Procamallanus (Spirocamallanus) chetumalensis n. sp. is described from the
      stomach and intestine of the Mayan sea catfish Ariopsis assimilis (Gunther,
      1864), from the Bay of Chetumal, Quintana Roo, Mexico. It is characterized by
      bifurcate deirids; males have 3 pairs of preanal papillae, 6 pairs of postanal
      papillae, 2 pairs of transverse elongate adanal papillae surrounding the cloacal
      aperture, wide caudal alae, spicules of unequal length, and a gubernaculum, and
      females have a rounded tail bearing a digit-like process terminating in 2 spines.
      This is the seventh Procamallanus (Spirocamallanus) species reported from fishes
      in Mexico and the first one recorded in sea catfishes of the Ariidae.

PMID- 12197128
TI  - Molecular phylogenetic analysis of the avian malarial parasite Plasmodium
      (Novyella) juxtanucleare.
AB  - Plasmodium (Novyella) juxtanucleare is a widely distributed parasite that
      primarily infects chickens (Gallus gallus domesticus). All species of Novyella
      are characterized by very small schizonts, which in the case of P. juxtanucleare
      are always found juxtaposed to the erythrocyte nucleus, hence its name. Nearly
      complete small-subunit ribosomal RNA sequences have been obtained from 2 isolates
      of this species, and comparisons with other Plasmodium species have been made.
      Phylogenetic analysis reveals that this parasite is closely related to other
      avian-infecting Plasmodium species and that molecular relationships among the
      avian-infecting plasmodia do not correspond to their morphology-based subgeneric
      classifications.

PMID- 12197126
TI  - Identification of Taenia asiatica in China: molecular, morphological, and
      epidemiological analysis of a Luzhai isolate.
AB  - Multiple analysis has characterized a recently described tapeworm of people,
      Taenia asiatica, in mainland China. Six adult tapeworms collected from people of
      the Zhuang minority residing in the southern part of China (Luzhai isolate) were
      comparatively analyzed with other tapeworms from people: T. asiatica (n = 2,
      South Korea), T. saginata (n = 1, Poland; n = 1, Korea), and T. solium (n = 1,
      People's Republic of China). Experimental infections with eggs from the Luzhai
      isolate in pigs and cattle produced cysticerci, each with a hookletless scolex
      and with wartlike formations on the external surface of the bladder wall. There
      were rostellar protrusions in the scolices of adult worms. Random amplified
      polymorphic DNA analysis using 3 arbitrary primers produced bands identical to
      those of the Korean T. asiatica. Conversely, T. saginata and T. solium exhibited
      different banding patterns. Phylogenetic relationships inferred from the complete
      nucleotide sequences of the internal transcribed spacer 2 placed the Chinese
      tapeworms consistently within the T. asiatica clade by 96% bootstrapping value in
      the maximum likelihood analysis, 96% in maximum parsimony, and 100% in neighbor
      joining. These collective data demonstrate that T. asiatica is sympatrically
      distributed with the other 2 species of Taenia in the human host in mainland
      China.

PMID- 12197129
TI  - Neophilometroides n. gen. (Nematoda: Philometridae) for Philometroides caudatus
      Moravec, Scholz and Vivas-Rodriguez, 1995, with erection of Neophilometroidinae
      n. subfam.
AB  - A detailed examination (including scanning electron microscopy) of newly
      collected nematode specimens (subgravid females) referable to Philometroides
      caudatus Moravec, Scholz and Vivas-Rodriguez, 1995, from the swimbladder of the
      pimelodid catfish, Rhamdia guatemalensis, in the Papaloapan River in Tlacotalpan,
      State of Veracruz, Mexico, as well as the paratype specimens of this species,
      revealed the presence of a small buccal capsule armed with peribuccal teeth in
      the female. Because of this unique morphological feature within the
      Philometridae, and considering other taxonomically important characters such as
      the structure of the male tail and the shape of the anterior end of the esophagus
      in the gravid female, Neophilometroidinae n. subfam, and Neophilometroides n.
      gen. are proposed to accommodate this species. Philometra paraguayensis Petter,
      1995, is transferred to Neophilometroides as N. paraguayensis (Petter, 1995) n.
      comb. Newly collected specimens are briefly described and illustrated.

PMID- 12197130
TI  - Hepatozoon species (Apicomplexa: Hepatozoidae) of the corn snake, Elaphe guttata
      (Serpentes: Colubridae) and the pigmy rattlesnake, Sistrurus miliarius barbouri
      (Serpentes: Viperidae) in south Florida.
AB  - Hepatozoon guttata n. sp. is described from the corn snake (Elaphe guttata
      guttata) from south Florida. Gamonts average 14.6 x 4.6 (13-17 x 3.5-6) and are
      not recurved, with nucleus situated in the second quarter of the gamont.
      Erythrocyte cytoplasm rarely appears partially dehemoglobinized. The infected
      cells are usually distorted and are longer than the uninfected erythrocytes but
      do not differ in width; nuclei are smaller in length and width than those of
      uninfected cells. Sporogony in Aedes aegypti occurs within the head and the
      thorax but rarely in the abdomen. Oocysts are spherical to usually ovoid, 87.2 x
      75.9 (45-155 x 40-152.5) and contain on average 7.1 (2-32) sporocysts. Sporocysts
      are spherical to ovoid, 34.8 x 31.0 (20-55 x 17.5-47.5), with 45.7 (14-89)
      sporozoites contained within. The pigmy rattlesnake (Sistrurus miliarius
      barbouri) in south Florida is parasitized by H. sistruri n. sp. Gamonts average
      14.1 x 5.6 (12.6-15.8 x 4.7-6.3) in breadth and are not recurved, with the
      nucleus always situated in the second quarter of the gamont commonly at the
      midbody. Erythrocyte cytoplasm is not dehemoglobinized. The infected cells are
      always distorted and similar in length to the uninfected cells but with greater
      width and enlarged nuclei. Sporogony in A. aegypti occurs within head, thorax,
      and abdomen. Oocysts are spherical to usually ovoid, 163.6 x 154.7 (92-245 x 82
      240) and contain 27.4 (12-42) sporocysts. Sporocysts are round to usually ovoid,
      39.7 x 33.5 (25-50 x 20-50), with 45.7 (19-70) sporozoites.

PMID- 12197131
TI  - The status of Haemogregarina mansoni Sambon and Seligmann from Zamenis
      flagelliformis Laurenti.
AB  - Haemogregarina mansoni Sambon and Seligmann 1907, a parasite of the coachwhip
      snake (Masticophis flagellum) is redescribed on the basis of sporogonic stages
      obtained in the experimental vector Aedes aegypti and designated as Hepatozoon
      mansoni from hosts collected in north Florida. Gamonts average 14.7 x 4.7 (13-16
      x 4-6) and are not recurved, with nuclei situated in the second quarter of the
      gamont. Erythrocyte cytoplasm is often thin, appearing partially
      dehemoglobinized, or contracted into a central mass with infected erythrocytes
      always distorted, longer, and more slender than uninfected cells. Sporogony
      occurred within the head and thorax of A. aegypti. Oocysts were spherical to
      ovoid, 144.2 x 126.1 (79-198 x 69-178), containing on average 29.2 (7-64)
      sporocysts. Sporocysts were spherical to ovoid, 33.1 x 29.8 (19-48 x 18-44), with
      20.2 (12-32) sporozoites contained within. Experimental infection in Tantilla
      relicta produced gamonts that did not differ from those in M. flagellum, but
      dehemoglobinization and cytoplasmic contraction of the host erythrocyte did not
      occur, and persistent merogonic stages were not present in the tissues.

PMID- 12197132
TI  - Efficacy of oral sulfadimethoxine against two gregarine parasites,
      Protomagalhaensia granulosae and Gregarina cubensis (Apicomplexa: Eugregarinida),
      infecting the Death's Head cockroach, Blaberus discoidalis.
AB  - Gregarines are common parasites of insects in culture, but no effective
      chemotherapeutic or prophylactic control protocol has been demonstrated.
      Sulfadimethoxine was administered in 5- and 7-day treatments to Death's Head
      cockroaches (Blaberus discoidalis) infected with Gregarina cubensis and
      Protomagalhaensia granulosae to test the efficacy of this sulfonamide against
      gregarine infection. Sulfadimethoxine significantly reduced the mean intensity of
      both G. cubensis and P. granulosae. Sulfadimethoxine treatment reduced gregarine
      intensity by 80% to 85% but had no significant effect on gametocyst production,
      suggesting that sulfonamide toxicity is directed primarily at sporozoites,
      trophozoites, and perhaps young gamonts. The possible use of sulfadimethoxine to
      produce gregarine-free insect cultures and the potential utility of gregarines as
      target organisms for screening pharmacologically active compounds for use against
      other intestinal apicomplexans are discussed.

PMID- 12197133
TI  - Examination of attachment and survival of Toxoplasma gondii oocysts on
      raspberries and blueberries.
AB  - The consumption of Toxoplasma gondii oocysts on fresh produce may be a means of
      its transmission to humans. Cats shed T. gondii oocysts, which contaminate
      produce directly or contaminate water sources for agricultural irrigation and
      pesticide and fertilizer applications. Cyclospora cayetanensis is a related
      coccidial parasite, and outbreaks of diarrhea caused by C. cayetanensis have been
      associated with the ingestion of contaminated raspberries. The oocysts of these
      coccidians are similar in size and shape, indicating that they may attach to and
      be retained on produce in a similar manner. In the present study the attachment
      and survival of T. gondii oocysts on 2 structurally different types of berries
      were examined. Raspberries and blueberries were inoculated individually with 1.0
      x 10(1) to 2.0 x 10(4) oocysts of sporulated T. gondii. Berries inoculated with
      2.0 x 10(4) oocysts were stored at 4 C for up to 8 wk. Oocyst viability and
      recovery were analyzed by feeding processed material to mice. Mice fed T. gondii
      inoculated berries stored at 4 C for 8 wk developed acute infections. In other
      experiments mice fed raspberries inoculated with > or = 1.0 x 10(1) oocysts
      became infected, whereas only mice fed blueberries inoculated with > or = 1.0 x
      10(3) oocysts became infected. This study demonstrates that T. gondii oocysts can
      adhere to berries and can be recovered by bioassays in mice and that raspberries
      retain more inoculated oocysts than do blueberries. The results suggest that T.
      gondii may serve as a model for C. cayetanensis in food safety studies.

PMID- 12197134
TI  - Total anaerobiosis during in vitro culture in conventional cell culture media is
      required for retaining infectivity of Trichinella spiralis L1 larvae.
AB  - The infectivity of Trichinella spiralis L1 larvae was examined in Swiss CD-1 mice
      after their maintenance in conventional cell culture media under different
      atmospheric conditions. Larvae isolated from the infected mouse carcasses were
      cultured for 24 hr in Roswell Park Memorial Institute (RPMI) medium, minimum
      essential medium (MEM), 199 medium, and Hank's balanced salt solution (HBSS)
      medium under anaerobic, microaerobic, and 5% CO2 conditions. Only those larvae
      maintained under anaerobiosis in all media retained their infectivity in mice.
      The larvae maintained microaerobically and under 5% CO2 lost more of their
      infectivity when cultured in RPMI medium and MEM (> 96%) than in 199 and HBSS (>
      78%).

PMID- 12197135
TI  - Comparison of the significance of CD4+ and CD8+ T lymphocytes in the protection
      of mice against Encephalitozoon cuniculi infection.
AB  - The role of T lymphocyte subpopulations in the protection against intraperitoneal
      (i.p.) and peroral Encephalitozoon cuniculi infections was compared in adoptive
      transfer experiments using severe combined immunodeficient mice. Whereas CD8+ T
      cell-depleted, but not CD4+ T cell-depleted, BALB/c splenocytes failed to protect
      the mice against i.p. infection, only SCID mice reconstituted with both CD4+ T
      lymphocyte- and CD8+ T lymphocyte-depleted splenocytes succumbed to peroral
      infection. The results indicate that whereas CD8+ T cells are critical for the
      protection against an i.p. E. cuniculi infection, both CD4+ and CD8+ T lymphocyte
      subpopulations play a substantive protective role in a peroral infection, i.e.,
      natural route of infection.

PMID- 12197136
TI  - Introduction of the exotic tick Amblyomma hebraeum into Florida on a human host.
AB  - A resident of Florida returned from a short visit to southern Africa to find a
      male Amblyomma hebraeum tick attached to the skin behind her knee. Amblyomma
      hebraeum is a major vector of 2 pathogens that cause important diseases in
      southern Africa, heartwater of ruminants and African tick-bite fever of humans.
      The tick was tested by polymerase chain reaction assay for evidence of infection
      with Cowdria ruminantium and Rickettsia africae (the causative agents of heart
      water and African tick-bite fever, respectively) and was found to be negative for
      both agents. This is the second record of the exotic tick, A. hebraeum, being
      introduced into the United States on a human host.

PMID- 12197137
TI  - Prevalence of Toxoplasma gondii antibodies in domestic cats from rural Ohio.
AB  - Antibodies to Toxoplasma gondii were determined in serum samples from 275
      domestic cats from a mobile spay and neuter clinic from 8 counties in Ohio. The
      modified agglutination test incorporating whole formalinized tachyzoites and
      mercaptoethanol was used to determine antibodies. Antibodies to T. gondii were
      found in 133 (48%) out of 275 cats: in titers of 1:25 in 24, 1:50 in 37, and
      1:500 or more in 72. The highest prevalence (62% of 78) was in outdoor cats. The
      prevalence of T. gondii antibodies in 48% of cats suggests wide-spread
      contamination of the rural environment with oocysts.

PMID- 12197138
TI  - Microplate method for obtaining Leishmania clonal populations.
AB  - The various clinical expressions observed in human leishmaniases result from
      complex host-parasite relationships in which the biodiversity of the parasite is
      a determining factor. Because Leishmania strains isolated from humans are
      composed of heterogeneous populations, it is crucial to use clonal lineages for
      studies on the characterization of these parasites. Presently, techniques used
      for cloning Leishmania spp. parasites are time-consuming and show poor
      efficiency. Here, a method developed in 96-well microplates is described, which
      allows one to rapidly obtain numerous clones of Leishmania in the most versatile
      and efficient way. The technique may be useful for cloning various protozoa as
      well as Leishmania spp.

PMID- 12197139
TI  - Development and evaluation of an enzyme-linked immunosorbent assay with
      recombinant SAG2 for diagnosis of Toxoplasma gondii infection in cats.
AB  - Cats are pivotal in the transmission of Toxoplasma gondii. To develop a sensitive
      and specific serodiagnostic method for feline toxoplasmosis, surface antigen 2
      (SAG2) of T. gondii was expressed in Escherichia coli and its diagnostic
      potential evaluated in an enzyme-linked immunosorbent assay (ELISA). The ELISA
      with recombinant SAG2 (rSAG2) was able to differentiate very clearly between sera
      from cats experimentally infected with T. gondii and sera from normal cats. Serum
      samples collected from domestic cats in Japan were investigated by the ELISA, and
      the results were compared with those of a commercially available latex
      agglutination test (LAT) kit. Of the 192 samples screened, 42 (21.9%) were
      positive by ELISA. Among the 42 ELISA-positive samples, 39 were positive by LAT.
      There was a significant correlation between ELISA and LAT titers. All the 150
      ELISA-negative samples were negative by LAT. These results indicate that the
      ELISA with rSAG2 expressed in E. coli should be a useful method for detection of
      T. gondii infection in cats.

PMID- 12197140
TI  - Efficient polymerase chain reaction detection of the second internal transcribed
      spacer of mucosa-derived larvae is dependent on the larval extraction method.
AB  - Methods for estimating abundance of arrested gastrointestinal larvae in large
      mammal hosts by digestion of the gastrointestinal mucosa are well established.
      The effects of digestion on the success of species identification using the
      polymerase chain reaction (PCR) are, however, unknown. In this study, the
      relationship between numerical recovery of arrested larvae and the success of PCR
      typing for the second internal transcribed spacer of ribosomal genes was
      characterized. Fresh and prefrozen mucosa of 4 sheep yielded very similar rates
      of recovery and PCR detection. When sheep mucosa were digested with neutral N
      acetyl cysteine, recovery increased, whereas PCR detection remained constant (60
      80%) with digest duration (1-16 hr). In contrast, when sheep and Svalbard
      reindeer mucosa were digested with acid-pepsin, recovery increased, whereas PCR
      detection declined to 0 with digest duration. Thus, to optimize recovery and PCR
      analysis of arrested gastrointestinal nematode larvae, acid-pepsin digestion of 1
      2 hr for PCR detection and 16 hr for recovery, or neutral N-acetyl cysteine
      digestion of 8-16 hr for both assays, should be used.

PMID- 12197141
TI  - Gynandromorphism in Amblyomma cajennense and Rhipicephalus sanguineus (Acari:
      Ixodidae).
AB  - During a survey of ticks on horses in November 2000, at the University of Sao
      Paulo farm in Pirassununga county, Sao Paulo, Brazil, 1 gynandromorph of
      Amblyomma cajennense was collected from a naturally infested horse. In another
      survey on dogs in March 2001, in the urban area of Monte Negro, Rondonia, Brazil,
      a gynandromorph of Rhipicephalus sanguineus was collected from a naturally
      infested dog. Both specimens are described and classified as perfect bipartite
      protogynanders.

PMID- 12197142
TI  - Effects of gamma radiation on viability of Encephalitozoon spores.
AB  - Spores of Encephalitozoon cuniculi, E. hellem, and E. intestinalis harvested from
      cultured mammalian cells were suspended in deionized water, exposed to gamma
      irradiation at doses of 0-3.0 kGy, and then tested for infectivity by inoculating
      spores into monolayer cultures of Madin-Darby bovine kidney cells. The cultures
      were examined for developing microsporidia 4 days later. As the dosage level of
      radiation increased, corresponding decreases were observed in the number of
      developing microsporidia for all 3 species. For E. cuniculi and E. intestinalis,
      100% inhibition of development was observed after exposure to 1.5 and 2.0 kGy,
      respectively. Although development of E. hellem was greatly inhibited (97.6%
      inhibition) after exposure to 3.0 kGy, complete inhibition was not obtained.
      These findings provide a baseline for investigating the dose levels required to
      render food products safe when kept under varying temperature, moisture, and
      other storage conditions.

PMID- 12197143
TI  - Reproductive strategies of the seabird tick Ixodes uriae (Acari: Ixodidae).
AB  - Ixodes uriae is a common ectoparasite of colonial seabirds in the circumpolar
      areas of both hemispheres. Despite its potential effects on host population
      dynamics and its role as a vector of pathogens, little is known about the
      reproductive strategies of this tick under natural conditions. Multiple mating of
      engorged females has been recorded in several instances, but the resulting
      paternity of offspring and its potential evolutionary significance have never
      been evaluated. Here, the paternity of offspring produced by females collected in
      the field was determined by using 5 polymorphic microsatellite markers. The
      results indicate that multiple mating in I. uriae can lead to multiple paternity
      in broods and, given the life history of this parasite, may be related to the
      adaptive benefits of producing genetically diverse offspring. Copulations took
      place both before and after the female's blood meal, but most successful
      fertilizations seemed to occur before engorgement. This suggests that the mating
      strategies of this tick may have evolved in response to local environmental
      constraints and, in particular, to the availability of conspecific ticks.

PMID- 12197144
TI  - Nonrandom association patterns in parasite infections caused by the host life
      cycle: empirical evidence from Kudoa camarguensis (Myxosporea) and Aphalloides
      coelomicola (Trematoda).
AB  - Pomatoschistus microps is 1 of the most common fish species inhabiting
      Mediterranean coastal lagoons. This small species uses an early maturation and a
      short life span to occupy sites subject to high variability in environmental
      factors. During monthly investigations on a P. microps population of the Vaccares
      Lagoon from March 1993 to December 1997, 2 conspicuous parasites were noticed.
      The digenean Aphalloides coelomicola was harbored in the abdominal cavity of the
      fish, whereas the myxosporean Kudoa camarguensis was found in the muscle tissues.
      Monthly peaks of prevalence occurred at the same period for both parasites, and a
      positive correlation (permutation test and Janson and Vegelius correlation) was
      observed between their occurrences among sampled fish. These results suggest that
      this positive association is related to a third common factor, i.e., their host's
      life cycle.

PMID- 12197145
TI  - A comparative analysis of PCR-based detection methods for avaian malaria.
AB  - Here, 4 polymerase chain reaction (PCR) assays are compared to test for the
      presence of avian malaria, including both the Plasmodium and Haemoproteus genera,
      in 29 different species of African rainforest birds. Two of these PCR assays use
      primer sets that amplify fragments of the cytochrome b (cyt b) gene of
      Plasmodium; the other 2 target the 18S ribosomal subunit gene. These PCR assays
      were performed using genomic DNA extracted from blood and subsequently compared
      with the results obtained by microscopic examination of blood smears taken from
      the same individuals. The 2 primer sets amplifying the cyt b gene were found to
      perform more reliably than those that target the 18S rRNA gene and yielded a
      substantial number of positive samples that were undetected by blood smear
      analysis. Of all the individuals screened by PCR, 40% tested positive for avian
      malaria, whereas 27% tested positive by blood smear analysis. Although sequence
      variation in the parasites may prohibit the specific alignment of primers and the
      subsequent PCR amplification of some individuals, PCR, once optimized, is faster,
      cheaper, and more reliable than blood smear analysis for large-scale screening.

PMID- 12197146
TI  - Allozyme markers for the identification of Lecithochirium rufoviride and
      Lecithochirium furcolabiatum (Trematoda: Hemiuridae), parasites of Conger conger
      and Anguilla anguilla from Atlantic Spanish waters.
AB  - The allozyme variation between 2 sympatric populations of Lecithochirium
      furcolabiatum and L. rufoviride was examined with the aim to investigate if the
      2, morphologically similar, helminths are reproductively distinct. Three enzyme
      loci, Gpd, Pgm-1, and Idh were found to be diagnostic for the 2 species. These
      results support the conclusion that the worms are different biological species.
      Only the Gpi and Gdh loci showed no differences. Marked genetic subdivision was
      detected at the Idh locus in the L. rufoviride population. Given that the
      genotypic distribution at Pgm-I showed no significant deviations from Hardy
      Weinberg expectations, it does not appear that the absence of heterozygotes for
      Idh was caused by the reproductive structure of the population. Although there
      are several other possible reasons for the deficiency of heterozygotes in natural
      populations, the existence of a new noninterbreeding group within the population
      studied constitutes a plausible explanation.

PMID- 12197148
TI  - Open dialogues with good and poor outcomes for psychotic crises: examples from
      families with violence.
AB  - In Open Dialogue the first treatment meeting occurs within 24 hr after contact
      and includes the social network of the patient. The aim is to generate dialogue
      to construct words for the experiences embodied in the patient's psychotic
      symptoms. All issues are analyzed and planned with everyone present. A dialogical
      sequence analysis was conducted comparing good and poor outcomes of first-episode
      psychotic patients. In good outcomes, the clients had both interactional and
      semantic dominance, and the dialogue took place in a symbolic language and in a
      dialogical form. Already at the first meeting, in the good outcome cases, the
      team responded to the client's words in a dialogical way, but in the case with
      the poor outcome, the patient's reflections on his own acts were not heard.

PMID- 12197147
TI  - Lung-stage protein profile and antigenic relationship between Ascaris
      lumbricoides and Ascaris suum.
AB  - The protein profile and antigenic properties of lung-stage larvae of Ascaris
      lumbricoides and A. suum were studied using 2-dimensional electrophoresis and
      immunoblot analysis, respectively. The protein profiles of the 2 parasites were
      identical except for the presence of only 1 major protein spot specific for each.
      There was a complete cross-reactivity between the 2 parasites at the
      immunological level, and no specific antigen was recognized using specific
      antibody raised against the 2 parasites in rabbits.

PMID- 12197149
TI  - Listening with integrity: the dialogical stance of Jaakko Seikkula.

PMID- 12197150
TI  - In the space between people: Seikkula's open dialogue approach.

PMID- 12197152
TI  - "Languaging" factors affecting clients' acceptance of forgiveness intervention in
      marital therapy.
AB  - Forgiveness is a significant intervention for healing interpersonal injury. Yet
      therapists do not often use forgiveness intervention. Employing a semantic
      perspective and a survey design (n = 307), this study investigated whether the
      language used to rationalize forgiveness intervention (set at five levels:
      personal growth, relationship reconciliation, spiritual issue, others' growth,
      and pardoning/condoning) may affect its acceptability. Gender, problem type, and
      choice were also included in the analyses. Overall, forgiveness was found to be
      an acceptable intervention. A pardoning/condoning rationale led to significantly
      lower acceptability ratings. Other results are discussed. We conclude that
      therapists should be less apprehensive about using forgiveness, but need to
      inform themselves better concerning its purpose, process, and articulation.

PMID- 12197153
TI  - Marital distress, co-occurring depression, and marital therapy: a review.
AB  - This article reviews several factors that contribute to marital distress and co
      occurring depression and also reviews empirically supported therapies. Gender
      contributes to marital distress and depression but does not appear to be the
      cause of either. Marital distress and depression appear to have bidirectional
      influence on each other. The depressed spouse's depression has a marked impact on
      the marital adjustment of the nondepressed spouse. Both marital distress and
      depression appear to be chronic. It is recommended that treatment be designed to
      help couples be supportive of each another, to adapt, and to cope with the
      depressive symptoms within the framework of their ongoing marital relations.

PMID- 12197154
TI  - Couple dynamics and attributions when one partner has an acquired hearing loss:
      implications for couple therapy.

PMID- 12197155
TI  - Walls and bridges: how coupled gay men and lesbians manage their
      intergenerational relationships.
AB  - Eighty respondents in 20 gay male and 20 lesbian couples were interviewed in
      depth to determine the nature and influences of their intergenerational
      relationships. Most respondents reported that their partner relationships were
      not affected by parental disapproval. Both the lesbian and gay male participants
      assertively defended the emotional, intergenerational boundaries around their
      unions. However, the gay men emphasized the importance of independence from their
      parents, whereas the lesbians sought harmonious intergenerational connections.
      The findings suggest how Bowen's ideas about intergenerational relationships may
      need to be modified to reflect the gender-specific ways coupled gay men and
      lesbians manage their family relationships.

PMID- 12197156
TI  - Caregiving role affects family relationships of African American grandmothers as
      new mothers again: a phenomenological perspective.
AB  - Currently, African American grandmothers are becoming caregivers to grandchildren
      whose parents, for various reasons, are not providing them with adequate care.
      Replacing their adult children, as parents, while continuing to mother them along
      with caring for grandchildren are essential components of this complex situation.
      A part of the findings from this qualitative study of the experience of
      grandmother caregivers indicated that family relations are affected with their
      grandchildren, the parents of their grandchildren, and their other adult
      children. Implications for culturally sensitive, family-centered clinical
      practice and future research are discussed.

PMID- 12197157
TI  - Parents' and children's perceptions of family processes in inner-city families
      with delinquent youths: a qualitative investigation.
AB  - This study explored youths' and parents' perceptions of family interaction
      processes as well as the broader social and cultural factors that influence
      family functioning in a multiethnic sample of inner-city families with delinquent
      youth. In-depth interviews were conducted with 61 male youths and 33 parents
      predominantly from minority families. Guided by an ecological framework,
      qualitative data analyses were employed to explore individual and contextual
      factors that were perceived either to foster or to impede individual and family
      functioning. Findings supported previous empirical research highlighting the
      importance of family interaction processes in the lives of delinquent youths.
      Analysis of parent and youth data revealed important relationships among the
      individual, family, and community domains. The emphases placed on these
      interrelationships, however, varied in distinct and notable ways for parents and
      youths. The implications of these divergent patterns for family-level
      interventions are addressed.

PMID- 12197158
TI  - Events and experiences impacting the development of clinical self confidence: a
      study of the first year of client contact.
AB  - Research was conducted to identify the events and experiences influencing the
      development of clinical self-confidence during the first year of client contact
      for beginning marriage and family therapists. Thirty-nine recent graduates of a
      master's degree training program participated in a semistructured interview in
      which they were asked to describe the influences on their clinical self
      confidence. Through qualitative analysis, four event and experience categories
      emerged as exerting the most influence on confidence at this stage of
      professional development: supervision, contact with clients, contact with peers,
      and personal life stress. The authors recommend providing strength-focused
      supervision, acknowledging the effects of client contact, encouraging peer
      contact, and attending to personal life stress.

PMID- 12197159
TI  - Multi-stage augmentation of a narrow lip by the V-Y advancement.
AB  - The author describes in the present article a possible surgical procedure using
      multistage V-Y shift for the correction of narrow lips. His work is based on long
      lasting experience assembled during surgery of facial clefts and corrections of
      post-traumatic conditions. He emphasizes some advantages of the described
      procedures and the importance of carefully selected indications for its
      application.

PMID- 12197160
TI  - The role of plastic surgery in the complex treatment of breast tumours (review of
      indications and operations).
AB  - The indications and possibilities of plastic surgery are detailed for the
      treatment of benign and malignant breast tumours and precancerous. The necessity
      of perfect surgical technique and results is emphasized with regard to the
      somatopsychosocial response of these operations.

PMID- 12197161
TI  - Early and late fatal complications of inhalation injury.
AB  - Severe inhalation injury causes a substantial deterioration in the prognosis and
      increases the general mortality of patients with extensive burns. Recently, in
      particular due to the development of invasive monitoring of patients and
      effective treatment of acute burn shock, we encounter with increasing frequency
      patients who survive the acute stage, including complications such as ARDS, and
      reach the stage of late complications. The latter include tracheooesophageal
      fistulas that develop on the basis of pressure ulcers and chondromalacia, usually
      at the site of the balloon of the tracheostomic cannula, and the overproduction
      of fibrous tissue in the area of the airways which leads to the development of
      stenosis, pulmonary fibrosis and bronchiectasia. Frequently, different early and
      late complications combine.

PMID- 12197162
TI  - Successful treatment of a critically burnt neonate (case-report).
AB  - In a health institution in 2000, a premature neonate suffered critical burns. In
      the submitted case-report the authors describe the successful treatment of this
      quite exceptional case. Indirectly, they thus also draw attention to the very
      positive role played by interdisciplinary collaboration under such unusual
      circumstances.

PMID- 12197163
TI  - Quality of prehospital management of patients with burn injuries--a retrospective
      study.
AB  - The authors evaluate the quality of burn patient management prior to admission to
      a specialized department. The most frequent mistake was found to be inadequate
      airway management (no intubation) and a lack of an i.v. line and volume
      resuscitation. These problems could be seen especially in the patients admitted
      to the specialized department as secondary transfers, following initial treatment
      in another healthcare facility. Prehospital care of the patients admitted as
      primary transfers was found to be satisfactory in the majority of cases. The
      authors conclude that some mistakes in diagnosis may be caused by the development
      of the burn over time as well as by the fact that certain clinical experience is
      necessary for determining the correct diagnosis. The predominant cause of
      inadequate management in patients with severe thermal injuries is underestimating
      the severity of the injury and ignorance of the possible consequences of
      inadequate management of the patients for transfer.

PMID- 12197164
TI  - The most frequent problems in the initial stage of burn management.
AB  - On the basis of three case reports discussed in the article, the authors
      demonstrate the most frequent serious drawbacks occurring in the initial stage of
      care of severely burned patients. The first case report highlights the importance
      of correct determination of the extent of the burn trauma, which should be
      correctly assessed by every first contact physician. The second case report
      demonstrates the need for adequate management of patients with severe burn trauma
      (especially airway management and i.v. establishment). In the third case (a
      little baby) again the need for correct patient assessment, timely airway
      management and beginning of resuscitation and especially of appropriate and
      immediate transfer of the burned patient to the specialized burn facility are
      highlighted.

PMID- 12197165
TI  - [Do not undervalue Czech scientific literature].

PMID- 12197166
TI  - [Blunt injuries of the iliac artery--case reports].
AB  - The authors describe three patients with blunt injuries of the iliac artery. They
      mention the causes and mechanism of their development, symptomatology, diagnosis
      and treatment. They draw attention to early diagnosis and an active approach;
      they discuss the type of vascular prosthesis and mention alternative therapeutic
      procedures. In all patients surgical treatment (resection and prosthesis of the
      affected part) led to favourable long-term results.

PMID- 12197167
TI  - [Injuries of extremity blood vessels, personal experience and results].
AB  - The authors evaluated the results achieved in 47 patients with injuries of the
      acral vesels where they performed a total of 50 vascular operations during the
      five-year period from 1998-2001. 21.3% injuries were part of multiple injuries.
      The mean period of hospitalization was 14.7 days. The 30-day mortality was 6.4%
      and the morbidity 12.8%. The upper extremity was saved in all instances (100%),
      the lower extremity in 77.3% of the injured. The reason for high amputations of
      the lower extremity were most frequently injuries of the popliteal artery
      associated with skeletal injury and extensive contusion of the soft tissues of
      the extremity. The authors discuss the optimal diagnostic and therapeutic
      procedures in injuries of the acral vessels. They emphasize a multidisciplinary
      approach without delay with early, frequently during the primary operation
      indicated fasciotomy, to prevent the development of compartment syndrome. The
      order of operations in concurrent injuries of the acral skeleton depends on the
      stage of ischaemia, type of injury and solution of the skeletal fractures. This
      type of injury frequently calls for repeated redressing in the operation theatre
      with repeated necrectomies of soft tissues to prevent infection which may prove
      fatal for the extremity. Injuries of the acral vessels should be nowadays treated
      in specialized departments with a 24-hour diagnostic and therapeutic
      traumatological service which comprises a highly specialized team of vascular
      surgeons.

PMID- 12197168
TI  - [AESOP 3000--computer-assisted surgery, personal experience].
AB  - At present the most widely used system of CAS is a vocally controlled manipulator
      of the laparoscope AESOP 3000 (Automated Endoscopic System for Optimal
      Positioning) which makes it possible to implement some operations without the
      assistance of another surgeon ("Solo-surgery"). Because of financial costs the so
      far little used equipment ZEUS or DA VINCI are already "master-slave" systems
      with several robot arms where the surgeon operates by means of manipulators in
      the controlling unit without direct contact with the patient. At the First
      Surgical Clinic, General Faculty Hospital and First Medical Faculty Charles
      Universitx the authors use the robot system AESOP 3000 since March 2000, in
      particular in laparoscopic gastric banding on account of obesity, in laparoscopic
      cholecystectomies, laparoscopic gastroenteroanastomoses and operations in the
      area if the hiatus. This system made it possible to reduce the number of
      assisting physicians. E.g. in gastric banding one assistant is sufficient, in
      laparoscopic cholecystectomy it is possible to operate only with a suture nurse.
      The application of AESOP is particularly useful in laparoscopic appendectomies
      and inguinal hernioplasties where it makes possible so-called "solo-surgery" or
      "one man surgery". No doubt, it is however necessary to have the possibility to
      call immediately another doctor to the operation theatre in case of necessary
      conversion of laparoscopy of laparotomy. The authors did not record any case of
      unwanted movement of the robot arm or another serious technical problem. As
      compared with a manually guided laparoscope during the use of AESOP the number of
      unwanted or inadequate shifts of the optical equipment or its angular rotation
      decreased considerably.

PMID- 12197169
TI  - [Care of ostomies and of patients with ostomies].
AB  - Patients with stomas have better care than ten years ago. Care is available to
      everyone who needs it and improved recently very rapidly and markedly in the
      Czech Republic. The authors describe briefly the history and present structure of
      stoma care.

PMID- 12197170
TI  - [Surgical treatment of renal carcinoma and thrombosis of the inferior vena cava].
AB  - INTRODUCTION: In Slovakia every year some 600 renal carcinomas are diagnosed.
      This number includes 5 to 10% carcinomas with a tumours thrombus is the renal
      vein or inferior vena cava. The objective of the present work is to describe
      diagnostic and surgical methods is patients with this disease. MATERIAL AND
      METHODS: The authors describe the surgical procedures, depending on the level of
      the tumours thrombus in the inferior vena cava in a group of 22 patients operated
      at the Urological department of the F. D. Roosevelt Hospital in Banska Bystrica
      in 1997 to 2001. RESULTS: In all 22 patients the tumours thrombus was removed
      along with the tumours kidney. In two instances the thrombus reached as far as
      the right atrium and in 4 patients with a tumours thrombus in a subdiaphragmatic
      position extracorporeal circulation was used. There was no death in conjunction
      with the surgical operation. There was one complication caused by haemorrhage
      which called for surgical revision. Eight patients died during the investigation
      period as a result of a relapse and generalization of the disease. CONCLUSION:
      Based on the authors' experience and data in the literature the authors recommend
      surgery of the kidney with a tumours thrombus of the inferior vena cava as safe
      treatment in special hospital departments.

PMID- 12197171
TI  - [Fournier's gangrene].
AB  - The authors present their own experiences with diagnostics and treatment of men
      with necrotising fasciitis of the scrotum (Fournier's gangrene). During 1995-2001
      8 men were treated for the above diagnosis at the Clinic of Urology, Faculty
      Hospital in Hradec Kralove. Six cases were patients with diabetes type II, in one
      patient we found during basic examinations a large tumour of the sigmoid and one
      patient was 7 days after total scrotal orchiectomy (because of prostatic
      adenocarcinoma). Repeated open revision under general anaesthesia was performed
      in all men with necessary necrectomy, testicles were intact (except a patient
      after orchiectomy). The infection was spread into the hypogastric area in two
      patients and in one patient spontaneous rupture of bulbar urethra occurred. By a
      combination of antibiotic therapy and repeated necrectomies, open wound healing
      and wet compresses we achieved cure of infection and granulations, which made
      final scrotal plastic surgery possible. From microbiological point of view it was
      mixed aerobic and anaerobic flora.

PMID- 12197172
TI  - [Surgical myocardial revascularization in a female patient with bilateral
      occlusion of the common carotid arteries].
AB  - Concurrent stenosis of the coronary and carotid circulation is one of the most
      serious disease. The authors describe the case of a 74-year old female patient
      with ischaemic heart disease with concurrent bilateral occlusion of the common
      carotid arteries. Surgical revascularization of the myocardium was made using
      extracorporeal circulation under general normothermia with protection of the
      heart muscle from ischaemia by the method of warm blood cardioplegia. In the
      discussion the authors analyze contemporary possibilities of surgical treatment
      of ischaemic disease (MIDCAB, OPCAB, operations with extracorporeal circulation)
      and emphasize the advantages and risks of different procedures.

PMID- 12197173
TI  - [Pneumoperitoneum without perforation of the digestive tract].
AB  - The authors present an account on 9 patients who were detected in their
      department during the nine-year period from 1991-2000 with the finding of
      pneumoperitoneum where perforation of the digestive tract was not proved. In 4 of
      them (44%) conservative treatment was used, in the remaining 5 patients (56%) the
      condition called for surgical revision. The latter was made as an acute operation
      in four patients because of signs of peritoneal irritation, in one only after 4
      days because of suspected tumours intestinal disease. As to the site of the
      assumed source of the non-perforation pneumoperitoneum we included 6 of them into
      the group abdominal area, (1x pneumatosis cystoides intestinalis, 1x aerogenic
      infection from a perforated abscess of the right liver lobe, 2x microtraumas of
      the wall of the cardio-esophageal transition with massive vomiting, 1x
      microtraumas of the lesser curvature of the stomach during extreme distension of
      the stomach after incorrect intubation and resuscitation, 1x passage of gas
      through the inflamed distended colonic wall in colitis), two patients into the
      thoracic area (1x in conjunction with pneumothorax, 1x with hydrothorax), 1
      patient in the urogenital area (by the gynaecological route after repeated coitus
      and orogenital practices). The authors summarize on the basis of data in the
      literature and their own experience diagnostic and therapeutic possibilities of
      this relatively rare finding.

PMID- 12197174
TI  - [Problems due to workload after surgical treatment of carpal tunnel syndrome].
AB  - The authors present a group of patients operated on account of the carpal tunnel
      syndrome in 1998-2000 at the Neurosurgical department in Pardubice. The group
      comprised 37 patients. 15 men and 22 women. The main objective of the
      retrospective investigation was to assess the period of work incapacity and asset
      of the operation from the aspect to proceed with the usual workload. The authors
      also tried to evaluate the effect of age, sex, occupation, preoperative clinical
      and electromyographic finding on the resulting effect of the operation. The
      period of work incapacity after one operation was 114 days. 84% patients returned
      to their original job. In 11% it was necessary to enlist in different work and a
      disability pension was granted to 5% patients. The discussion is focused on the
      period of work incapacity, enlistment in work, the effect of operation on the
      patients complaints and the objective finding as regards the lesion of fibres of
      the median nerve and also on the asset of EMG in the diagnosis and postoperative
      follow up.

PMID- 12197175
TI  - [Feeding jejunostomy and protective ileostomy in acute necrotizing pancreatitis].
AB  - The authors emphasize the complexity of the problem of treating acute necrotizing
      pancreatitis. On their own group of 52 operated patients during 1995-2000 they
      present the gradual, in 2000 dramatic, improvement of results in which
      participate in addition to modern therapeutic procedures also the concentrated
      interest in the problem and the personal experience of the surgeons.

PMID- 12197176
TI  - Resistant malaria in KwaZulu-Natal.

PMID- 12197177
TI  - Pregnancy and the PPS.

PMID- 12197178
TI  - HIV testing for rapists.

PMID- 12197179
TI  - Generic substitution of anti-arrhythmic drugs.

PMID- 12197181
TI  - Cash without capacity--the AIDS dilemma.

PMID- 12197180
TI  - Bone densitometry--role of quantitative computed tomography.

PMID- 12197182
TI  - Sibongile Manana determined to lose GRIP.

PMID- 12197183
TI  - Public drug shortages compromise care.

PMID- 12197184
TI  - Maternity hospital check-ups improve.

PMID- 12197185
TI  - 'PIL' dispensing regulations coming up.

PMID- 12197186
TI  - SAMA ethical guidelines on HIV research, education, prison life and public
      campaigns.

PMID- 12197187
TI  - The national telemedicine system in South Africa--an overview and progress
      report.

PMID- 12197188
TI  - Radiation risk in paediatric CT.

PMID- 12197189
TI  - The sexual and psychological implications of hysterectomy.

PMID- 12197190
TI  - Small-bowel strictures and perforation in tuberculosis.

PMID- 12197191
TI  - Choice of diuretics for treatment of essential hypertension.

PMID- 12197192
TI  - Mutations in prothrombin and factor V genes do not contribute significantly to
      placental vasculopathy in a high-risk patient cohort in South Africa.

PMID- 12197193
TI  - Trypanosomiasis--an unusual cause of reversible multiple organ dysfunction in
      South Africa.

PMID- 12197194
TI  - Symptoms of the bite of an orb-web spider Araneus apricus (Araneae: Araneidae).

PMID- 12197195
TI  - Comparison of indapamide and low-dose hydrochlorothiazide monotherapy in black
      patients with mild to moderate hypertension.
AB  - OBJECTIVES: To assess, using ambulatory blood pressure monitoring (ABPM), the
      antihypertensive efficacy of hydrochlorothiazide 12.5 mg and indapamide 2.5 mg
      given as a monotherapy over 3 months to black patients with mild to moderate
      essential hypertension. DESIGN: Single-centre, prospective, randomised open pilot
      study in three phases: (i) 1-week drug-free washout period; (ii) 2-week placebo
      run-in phase; and (iii) 3-month prospective open-label active treatment period.
      RESULTS: Forty-two black patients with mean daytime diastolic BP (DBP) > or = 90
      mmHg and < or = 115 mmHg (mean age 57 +/- 11 years, 28 women/14 men) were
      enrolled into the study. Overall, a profound and sustained BP reduction was
      achieved with indapamide at 3 months (N = 20). The 24-hour BP decreased from 150
      +/- 17/94 +/- 6 mmHg to 130 +/- 19/82 +/- 9 mmHg (P < 0.0001 for systolic BP
      (SBP) and DBP at 3 months versus baseline); the mean daytime BP decreased from
      155 +/- 15/98 +/- 6 mmHg to 134 +/- 18/87 +/- 10 mmHg (P < 0.0001 for SBP and DBP
      at 3 months versus baseline). The overall control (mean daytime DBP < 90 mmHg)
      and response (decrease in daytime DBP > or = 10 mmHg) rates achieved with
      indapamide were 10/20 (50%) and 13/20 (65%), respectively. In contrast,
      monotherapy with hydrochlorothiazide resulted in more modest BP reduction and
      control and response rates at 3 months (N = 22). The 24-hour BP decreased from
      147 +/- 14/94 +/- 7 mmHg to 139 +/- 19/88 +/- 2 mmHg (P < 0.05 for DBP at 3
      months versus baseline, P = NS for SBP); the mean daytime BP decreased from 151
      +/- 14/98 +/- 5 mmHg to 144 +/- 16/93 +/- 10 mmHg (P < 0.05 for DBP at 3 months
      versus baseline, P = NS for SBP). The corresponding control and response rates
      were 7/22 (32%) and 8/22 (36%). Both hydrocholorothiazide and indapamide caused
      significant hypokalaemia. CONCLUSIONS: Monotherapy with indapamide is associated
      with greater BP reduction and control and response rates than monotherapy with
      low-dose hydrochlorothiazide and may be an appropriate choice of antihypertensive
      diuretic therapy in black South African patients with mild to moderate
      hypertension.

PMID- 12197196
TI  - Diabetes in rural South Africa--an assessment of care and complications.
AB  - OBJECTIVES: To describe the diabetic population under care of the public health
      sector in a district in rural KwaZulu-Natal, to assess the nature of their care,
      their glycaemic control and the extent of their complications. SUBJECTS AND
      METHODS: Two hundred and fifty-three diabetic patients consecutively attending
      clinics for review were interviewed and examined, and where available a 12-month
      retrospective review of clinical records was performed. Random blood glucose,
      haemoglobin A1c (HbA1c) and urine albumin/creatinine ratio were assayed. RESULTS:
      Acceptable glycaemic control (HbA1c < 2% above normal population range) was found
      in only 15.7% of subjects (95% confidence interval (CI): 11.4-20.8%). Mean HbA1c
      was 11.3%. The prevalence of hypertension (blood pressure > or = 160/95 mmHg
      and/or prescribed antihypertensive medication) was 65.4% (CI: 59.0-71.1%). Of 129
      patients who were prescribed antihypertensives, 14.0% (CI: 8.5-21.2%) were
      normotensive (< 140/90 mmHg). Severe obesity was present in 36.5% (CI: 30.4
      42.9%). Rates of attendance for review and compliance with diabetic medications
      were high. Blood glucose monitoring was not regularly performed and medications
      were rarely modified. Complications were common and mostly undiagnosed.
      Retinopathy of any grade was found in 40.3% of patients (CI: 33.2-50.9%) and was
      severe enough to warrant laser photocoagulation in 11.1% (CI: 8.5-21.2%).
      Microalbuminuria was found in 46.4% (CI: 40.0-53.0%) and foot abnormalities
      attributable to diabetes in 6.0% (CI: 3.4-9.7%). CONCLUSIONS: Care and control of
      diabetes in this rural community is suboptimal. There is a need for primary care
      staff to focus on modifying prescriptions in the face of poor blood glucose
      control and/or uncontrolled hypertension. Additional training and support for
      nursing staff and education for patients will be central to achieving this level
      of intervention.

PMID- 12197197
TI  - The South African Community Epidemiology Network on Drug Use (SACENDU) project,
      phases 1-8--cannabis and Mandrax.
AB  - OBJECTIVE: To provide community-level public health surveillance information on
      cannabis and Mandrax (methaqualone) use and associated health and social
      consequences. DESIGN: A descriptive, epidemiological study of cannabis and
      Mandrax supply and demand indicators based on data gathered from multiple
      sources, including specialist treatment centres, trauma units, police records,
      and quantitative and qualitative studies of school students, sex workers, persons
      attending rave clubs, and arrestees. Networks were established at five sentinel
      sites to facilitate the collection, interpretation, and dissemination of data.
      RESULTS: Supply and demand indicators point to the widespread use of cannabis and
      Mandrax and significant increases in white pipe-related health and social
      problems. There has been an increase in the demand for treatment related to
      cannabis/Mandrax use, a high proportion of patients in trauma units who test
      positive for cannabis and/or Mandrax, and a high proportion of cannabis and
      Mandrax-positive arrestees. Although the use of cannabis is predominantly a male
      phenomenon and is widespread among young people, it occurs in all sectors of
      South African society. Mandrax users tend to be young, male, and coloured.
      CONCLUSIONS: Cannabis and Mandrax use has a number of implications for health and
      social policy, including the need to develop protocols for the identification and
      management of cannabis/Mandrax-positive trauma patients and arrestees. The study
      points to the need for further monitoring of cannabis and Mandrax use and the
      negative consequences associated with their use.

PMID- 12197198
TI  - Toxicological screening for drugs of abuse in samples adulterated with household
      chemicals.
AB  - OBJECTIVES: Urine samples that tested positive for two drugs of abuse, namely
      cannabis and methaqualone, were reassayed in the presence or absence of common
      household chemicals: Jik (sodium hypochlorite), Dettol (chloroxylenol), G-cide
      Plus (glutaraldehyde), Perle Hand Soap, ethanol, isopropanol and peroxide (20
      volumes). These chemicals are frequently used for the adulteration of urine
      samples. SETTING: Department of Pharmacology, University of Stellenbosch.
      METHODS: Household chemicals, at three different concentrations, were added to
      urine samples that tested positive for methaqualone and cannabis. Samples were
      reanalysed on an ETS Plus Analyser (Syva Company, San Jose, Ca.) using Emit drugs
      of-abuse urine test reagents. RESULTS: Most of the chemicals tested influenced
      the outcome of positive toxicological screening results for these drugs. G-cide
      (glutaraldehyde) and Perle Hand Soap had the largest effect (false-negative) on
      the methaqualone test. Dettol (chloroxylenol) and Perle Hand Soap had the largest
      effect on the cannabis test. Higher concentrations of the adulterant were not
      always an indication of the extent of modification of the test result. The
      addition of certain chemicals (ethanol, isopropanol and peroxide) to the urine
      samples tested for methaqualone interfered with the test to such an extent that
      it gave invalid test results.

PMID- 12197199
TI  - Prevalence of childhood disability in rural KwaZulu-Natal.
AB  - OBJECTIVE: To determine the prevalence of disability in children under 10 years
      of age in the Manguzi subdistrict, in order to inform the development of an
      appropriate rehabilitation service. SETTING: Twelve areas within the rural
      Manguzi subdistrict of the Jozini-Uthungulu district in the far north-east of
      KwaZulu-Natal. DESIGN: A descriptive study in two stages. The first stage
      identified children under the age of 10 years reported with a disability. For
      this stage, 12 community health workers (CHWs) were trained to use a validated
      '10-question' screening tool with probes, adapted to include the under-2-year age
      group. The second stage involved confirmation of actual disability by the Manguzi
      rehabilitation team. RESULTS: A total of 2,036 children were screened. Of these
      children, 168 were reported with a disability giving an overall rate of 83/1,000
      (95% confidence interval (CI): 71-95). The overall confirmed prevalence rate for
      children with disabilities under 10 years was 60/1,000 (95% CI: 50-71). The most
      prevalent disabilities were mild perceptual or learning disability (17/1,000),
      followed by cerebral palsy (10/1,000), hearing loss (10/1,000), moderate to
      severe perceptual disability (6/1,000) and seizure disorders (4/1,000).
      CONCLUSION: The prevalence of disabilities among children aged under 10 years is
      high. This has major implications for health, rehabilitation, welfare and
      educational services in rural areas. These implications must be addressed in
      order to develop appropriate rehabilitation services for children in rural areas.

PMID- 12197200
TI  - Snake and staff symbolism, and healing.
AB  - Since time immemorial the snake has been venerated as an enigmatic creature with
      supernatural powers. As a snake and staff symbol it is also traditionally
      associated with the healing arts, either as the single-snake emblem of Asklepios,
      or as the double-snake emblem (caduceus) of Hermes. The mythological basis for
      this symbolism is reviewed. The Asklepian emblem has been associated with health
      care since the 5th century BC, when Asklepios became accepted by the Greeks as
      the god of healing. Whether he was also an historical figure as healer in earlier
      ages is less certain. The origin of the double-snake emblem is shrouded in the
      mists of antiquity. In classical times it became the herald's wand of Hermes,
      messenger of the gods who guided departed souls to the underworld, and was seen
      as protector of travellers, shepherds and merchants. In the latter capacity
      Hermes also conveyed a negative connotation as protector of thieves. During the
      Middle Ages the caduceus became a symbol of the healing sciences (pharmacy and
      alchemy in particular), and today, although mythologically incorrect, it is in
      common usage in the health care field.

PMID- 12197201
TI  - [Immigrations from the perspective of demography. Impact on health].
AB  - Spain has been a crossroads, for confrontation and peaceful living-together. The
      problems arising from immigration as a mass phenomenon are characteristic of the
      present times. Variables which define the immigration phenomenon are the
      attraction to the economically developed countries with an active labour market,
      while it is inversely related to the distance from the departure countries. The
      phenomenon is also modified by positive influences as the common language, and by
      negative factors as the political or social instability. The aging of the
      populations in developed countries, and the need of labour market, stimulate the
      immigration phenomenon, which may affect to 2.3% of the population. The
      reproductive capacity of the population depends not only on biological
      determinants but also on the heterogeneous culture of immigration, because
      immigrants are candidates to become stable members of society. There is a logic
      of discrimination of those which are different. Thus, we need a legislation to
      establish their rights and duties, as well as an integration policy to favour the
      cultural diversity.

PMID- 12197202
TI  - [Epidemiology of hypertension in the elderly population of Spain].
AB  - About 68% of the Spanish elderly are hypertensives (> or = 140/90 mmHg). About
      65% are aware hypertensives, 55% are treated with antihypertensives, and only 16%
      are controlled. Among treated hypertensives, systolic control (32%) is much lower
      than diastolic control (82.3%). Control is lower in males, the oldest, and those
      of lowest educational level. About 57% of uncontrolled treated hypertensives are
      undergoing monotherapy. Losing weight is the least followed advice. Overall,
      hypertension is an important public health problem in the Spanish elderly.

PMID- 12197203
TI  - [HELLP syndrome and hemorrhagic gestosis].
AB  - In the year 1817, Charlotte daughter of Georges IV and princess of Wales, died on
      an unknown condition with uteroplacental hemorrhage and fetal death called at the
      time "Uteroplacental Apoplexy" and later "Abruptio Placentae". This affection was
      described in the classical books as an hemorrhagic complication of labor. In 1961
      we have at first related the Abruptio with acute toxemia (preeclampsia) and have
      proposed the term "Gestosis hemorragica" to design it. In 1982 Weinstein has
      described the called HELLP syndrome (Hemolysis, Elevated liver Enzymes, at Low
      Platelets) which basically is the same pathological picture as the described by
      us as "hemorrhagic toxemia". The aim of the paper is to demonstrate the identity
      of both syndromes and to claim for the priority of our definition.

PMID- 12197204
TI  - [Sanitary interest of carbonic, carbogaseous or acidulated waters].
AB  - The intention of this Communication is to highlight the main characteristics of
      the carbonic, carbogaseoses or acidulated waters of the Spanish legislation, as
      therapeutics agent as well as bottled drinking waters. These waters stimulate the
      secretion and motility of the digestive apparatus and if they are given by oral
      way in a correct amount, they have diuretic effects. In balneation they also
      introduce a vasodilatation, effect due to the penetration of the gas carbonic
      into the skin and its contact with the vascular walls, but this practice is not
      common in Spain.

PMID- 12197205
TI  - [Obstructive sleep apnea syndrome].
AB  - The obstructive sleep apnea syndrome (OSAS) is caused by an intermittent and
      repetitive obstruction of the upper respiratory tract during sleep, which leads
      to a complete (apnea) or partial (hypopnea) block of air flow. It is quite
      prevalent, being seen in 4-6% of males and 2% of females. Structural
      abnormalities present in the upper respiratory tract and obesity are the
      fundamental etiological factors. Clinical manifestations are due to sleep
      fragmentation and oxygen desaturation which cause the apnea. Day hypersomnia,
      snoring and episodes of apnea described by the spouse are the three basic
      symptoms. The diagnosis is based on polysomnography, which can be substituted for
      a night cardiorespiratory polygraphy. It has an important morbimortality rate,
      mainly due to traffic and labor accidents, ischemic heart disease and chronic
      respiratory failure. The treatment is multifactorial. First, eliminating alcohol
      and hypnotic drugs. Obesity, which is almost always present, must also be
      corrected. Structural abnormalities of the upper respiratory tract may require a
      surgical solution. The treatment preferred nowadays is the application of a nasal
      continuous positive airway pressure (CPAP) while the patient is asleep. It should
      be considered for those symptomatic patients with an apnea-hypopnea index over
      30, or if the index is below 30, than when a respiratory insufficiency or
      cardiovascular risk factors are present. In some cases surgical procedures may be
      considered, such as uvulopalatopharyngoplasty.

PMID- 12197206
TI  - [The conceptual revolutions about nature as imposed by 20th century physics].
AB  - A catalogue is offered of the thirteen conceptual--and observational--revolutions
      which took place in twentieth century Physics, those which should be considered
      the most revelant for their significance in the scientific and philosophical
      thought about Nature as established along that century. The are organized in the
      three areas where they were originated: Relativity, Quantum Physics and
      Cosmology. Several of these conceptual revolutions appeared in Physics
      explicitly, while the rest only happened to arise in a latent way. The ones and
      the others are remarked in this contribution with philosophical expressions and
      through the world horizon, a perspective which opens in a general manner each
      revolution to the whole of the scientific and philosophical of the past century.

PMID- 12197207
TI  - [Vascular canals. A model for the mandibular condyle growth].
AB  - The vascular or cartilage canals of the mandibular condyle were studied in human
      fetuses, whose ages extended from the 9th to the 13th week of development. The
      vascular canals are firstly constituted by an invagination of mesenchimal cells
      which is in connection with the mesenchimal layer of the condyle envelope. During
      the 11th week of development a vessel penetrates in the invaginations. In the
      12th and 13th weeks, the canals show a clearly defined pattern: some of them are
      located in the anterointernal region of the condyle, being those associated with
      the insertion of the lateral pterygoid muscle; two or three can be seen in the
      posterointernal region, whereas only one vascular canal, but th-e biggest one, is
      located in the posteroexternal region. This well defined disposition is related
      with the direction of the condylar growth during this period of the development.

PMID- 12197208
TI  - [Eugenio Gutierrez, count of San Diego, and his contribution to Spanish
      gynecology (150 years from his birth)].
AB  - The author presents the history of E. Gutierrez Gonzalez, born in Santander,
      Cantabria (Spain). He analyses Dr. Gutierrez's work and his contribution to the
      study of gynaecology as a new speciality in Spain. Gutierrez belonged to the
      positivist movement (1850-1914) when general surgery experienced a considerable
      boom with the arrival of antiseptics, asepsis and anesthesia. For 34 years, he
      was in charge of the Gynaecology Surgery Service in "El Instituto Rubio" of
      Madrid and doctor of the Royal House. There were also other relevant doctors at
      that time: Alonso Rubio, Fargas Roca, Recasens Girol in Gynaecology, and San
      Martin, Ribera and Cardenal in General Surgerie.

PMID- 12197209
TI  - [Biological security confronting bioterrorism].
AB  - A review is made on Biosecurity at both local and global level in relationship
      with Bioterrorism as a real threat and its control and prevention. The function
      of the network of High Security Laboratories around the world able to make
      immediate diagnosis, research on vaccines, fundamental and urgent epidemiological
      studies, conform a steady basis to control natural infections and also the
      possible bioterrorism attacks.

PMID- 12197210
TI  - [Cloning and stem cells. Social, ethical and moral impact].
AB  - Stem cells are non-specialised cells, but capable to develop into differenciated
      (or specialised) cells, that maintain a specific function until they die. Stem
      cells are obtained from blastocysts. Despite of their therapeutic potential,
      their origin has generated much controversy and confrontation because of ethical
      (and moral.) reasons. However, stem cells can also be supplied by adult cells,
      that are present in the tissue in a quiescient stage, waiting for the appropriate
      signals to develop into differenciated cells. This type cells is an alternative
      source for stem cells, and their utilization for medical treatment of
      degenerative diseases presents no ethical problems.

PMID- 12197211
TI  - Norwalk-like virus-associated gastroenteritis in a large, high-density encampment
      -Virginia, July 2001.

PMID- 12197212
TI  - National, state, and urban area vaccination coverage levels among children aged
      19-35 months--United States, 2001.

PMID- 12197213
TI  - Impact of vaccine shortage on diphtheria and tetanus toxoids and acellular
      pertussis vaccine coverage rates among children aged 24 months--Puerto Rico,
      2002.

PMID- 12197215
TI  - Contrast of response to dacarbazine, mitomycin, doxorubicin, and cisplatin (DMAP)
      plus GM-CSF between patients with advanced malignant gastrointestinal stromal
      tumors and patients with other advanced leiomyosarcomas.
AB  - BACKGROUND: Previous observations have suggested that leiomyosarcomas, and
      especially gastrointestinal leiomyosarcomas, may be less responsive to cancer
      chemotherapy than other histologic types of non-osseous sarcomas; however, this
      difference has not been characterized well until quite recently, with the
      recognition of the special identity of gastrointestinal stromal tumors (GIST).
      Prior to the general acceptance of this new histologic classification, we decided
      to study patients with gastrointestinal leiomyosarcomas in concert with other
      leiomyosarcomas for relative responsivity to a combination cytotoxic regimen
      developed specifically for leiomyosarcomas. PATIENTS AND METHODS: Adult patients
      with advanced leiomyosarcomas received intravenous chemotherapy as outpatients
      with dacarbazine 750 micrograms/m2, mitomycin 6 mg/m2, doxorubicin 40 mg/m2, and
      cisplatin 60 mg/m2 on day 0, with granulocyte macrophage colony stimulating
      factor (GM-CSF, sagramostim) 250 mcg/m2 given s.c. every 12 hr on days -6 to -3
      and on days 1-14 of each 4-week treatment cycle. Our original plan to escalate
      dacarbazine doses to 1000 mg/m2 following cycle one was abandoned after the first
      six patients because of toxicity. RESULTS: We studied 21 patients with GIST and
      18 patients with other types of leiomyosarcomas, for a total of 131 treatment
      cycles, with a median of four cycles per patient in each of the two groups of
      patients. Toxicity was significant, with 33% having grade 3 vomiting at some time
      during treatment. Grade 3 leukopenia occurred in 42%, and grade 3
      thrombocytopenia was observed in 68% of our patients. In one patient, grade 4
      pulmonary toxicity developed during the fourth cycle, and this was considered a
      major factor in her death. Objective tumor regression was observed in one of 21
      (1.8%) (95%CI = 0-14.5%) GIST and in 11 of 18 (61%) (95%CI = 38-84%) other
      leiomyosarcomas, including eight of 10 uterine cases. In five cases, we
      interrupted chemotherapy to attempt complete surgical excision of residual tumor,
      and four of the patients were rendered apparently free of disease. Median
      survivals for the two groups have been similar with 16.7 months (95%CI = 8.8-27.5
      months) for the GIST and 17.5 mos (95%CI = 10.9-35.3%) for the other
      leiomyosarcomas. Three patients with uterine leiomyosarcomas are still alive more
      than 2 years after completing this chemotherapy and subsequent secondary surgical
      excision (+/- irradiation) and two of them are free of disease. CONCLUSIONS:
      While this regimen is ineffective against GIST, its value against uterine
      leiomyosarcomas deserves further study in a larger population.

PMID- 12197216
TI  - Remission and survival following monthly intraarterial cisplatinum in
      nonresectable hepatoma.
AB  - PRECIS: Intraarterial delivery of 50 mg/m2 cisplatinum on a monthly basis is a
      well-tolerated regimen for patients with nonresectable hepatoma. The selective
      uptake of cisplatinum delivered intraarterially suggests other selective
      intraarterial protocols would be of use in regional cancers treated with
      cisplatinum. BACKGROUND: Sixty-seven patients with nonresectable hepatoma were
      treated with hepatic artery infusions (HAI) of 50 mg/m2 cisplatinum on a monthly
      basis. METHODS: Forty-eight patients received an initial course of whole liver
      external radiation with intravenous (i.v.) cisplatinum 50 mg/m2. Nineteen
      patients did not receive radiation and received HAI cisplatinum only. All
      patients then received HAI cisplatinum at 50 mg/m2 on a monthly basis. Six
      patients were given a tracer dose of radioactive 195m cisplatinum for
      quantitation by the HAI and i.v. routes. RESULTS: Monthly HAI cisplatinum was
      well tolerated and could be repeated indefinitely. Median survival for primarily
      treated nonresectable hepatomas was 12 months [alpha fetoprotein (AFP) elevated]
      and 17.5 months (AFP negative). Radioactive cisplatinum given by HAI yielded 34
      55% tumor uptake of cisplatinum vs. < 5% by i.v. delivery. CONCLUSIONS: Hepatic
      intraarterial cisplatinum at 50 mg/m2 is a well-tolerated monthly regimen for
      patients with nonresectable hepatoma.

PMID- 12197217
TI  - Clinical characteristics and treatment results of LMB/LMT regimen in children
      with non-Hodgkin's lymphoma.
AB  - Lymphomas are the second most common cancers after leukemias seen in children in
      Turkey, although they rank third in many western countries. Ninety-seven patients
      with newly diagnosed, untreated non-Hodgkin's lymphoma, between April 1994 and
      December 1997, were included in this study. Modified lymphoma malign B (LMB) and
      lymphoma malign T (LMT) regimens were used for treatment of B- and T-cell
      disease, respectively. Ten (10.3%), 68 (70.1%), and 19 (19.6%) patients had stage
      II, III, and IV disease, respectively. Forty-eight, 19, 15, 9, 5, and 1 patients
      had tumors at abdominal, mediastinal, disseminated, head and neck, extranodal,
      and peripheral nodal locations, respectively. Seventy-two patients were treated
      with LMB89 regimen and 25 were treated with LMT89 regimen. Thirty-four patients
      had tumor lysis at diagnosis, and 9 patients required dialysis. Objective
      response rates were 75% for patients treated by LMB regimen and 92% for those
      treated by LMT regimen. Two-year overall survival rates were 90, 66.1, and 50.8%
      for patients with stage II, III, and IV disease, respectively. Two-year overall
      survival rates were 64.2% for LMB-treated patients and 70.8% for LMT-treated
      patients. Poor response at the end of cytoreductive treatment and age younger
      than 4 years were poor prognostic factors. Pediatric lymphomas could be treated
      safely and effectively by LMB and LMT regimens.

PMID- 12197218
TI  - Phase I trial of oral estramustine and 3-hr infusional paclitaxel for the
      treatment of hormone refractory prostate cancer.
AB  - PRECIS: Estramustine 600 mg/m2 can be administered safely with 225 mg/m2 of
      paclitaxel if administered as a 3-hr infusion for the treatment of hormone
      refractory prostate cancer. Significant anti-tumor activity has been reconfirmed
      despite the change in schedule of administration of the paclitaxel. PURPOSE: This
      phase I study was conducted to identify the maximum tolerated dosage of
      paclitaxel administered as a 3-hr infusion combined with a stable dosage of
      estramustine capsules daily in men with hormone refractory prostate cancer. A
      secondary endpoint was to assess anti-tumor efficacy in this targeted patient
      population. PATIENTS AND METHODS: Twenty-six male patients, all with hormone
      refractory prostate cancer were enrolled in this trial. Estramustine was
      administered at a dosage of 600 mg/m2 daily, and paclitaxel was dose-escalated in
      cohorts from 125 to 250 mg/m2 administered as an infusion over 3 hr every 21
      days. Patients were treated until maximum response was achieved, or toxicity or
      progressive disease precluded further treatment. Toxicity to determine maximum
      tolerated dose was assessed only during the first 3-week cycle. RESULTS: The
      maximum tolerated dose of paclitaxel on this schedule was 225 mg/m2 based on
      unacceptable dose-limiting fatigue observed at the next higher dosage level.
      Other grade 3 or 4 events included myelosuppression, left ventricular
      dysfunction, elevated liver function tests, deep venous thrombosis, vomiting, and
      development of depression. Using a response criteria of prostate specific antigen
      decline of > 50% persisting for a minimum of 6 weeks, eight of 26 patients
      responded (30.8%). Two of seven patients with documented soft-tissue disease
      experienced > 50% reductions in size of lesions or number of sites. The median
      response duration was 6 months, and the median survival time was 16 months.
      CONCLUSION: The recommended phase II dose of paclitaxel is 225 mg/m2 when
      administered over 3 hr in combination with estramustine. This regimen has an
      acceptable toxicity profile, is a convenient schedule, and results in significant
      antitumor activity even in a heavily pre-treated population of patients.

PMID- 12197219
TI  - Phase I study of sequential administration of topotecan and 5-fluorouracil in
      patients with advanced malignancies.
AB  - Topotecan is a topoisomerase-I inhibitor, a drug that stabilizes a covalent
      complex of enzymes and causes strand cleavage of DNA. 5-Fluorouracil (5FU) is an
      antimetabolite that interferes with DNA synthesis. Preclinical studies using
      human cancer cell line models have shown potential therapeutic synergy between
      these two drugs by showing the maximum cytolytic effect using sequential 5FU
      followed by topotecan. In the current study, 5FU was used at a fixed dose of 375
      mg/m2 given intravenously for five consecutive days on a 28 day cycle. Topotecan
      was dose-escalated in cohorts of patients from 0.5 to 1.0 mg/m2 given
      intravenously for 5 days after the 5FU dose. Eleven patients were entered at
      different dose levels. Both hematological and gastrointestinal toxicity were dose
      limiting. Diarrhea was the dose-limiting toxicity at the dose of 0.75 mg/m2 of
      topotecan. Two cases of grade 4 neutropenia were also observed at this dose
      level. One patient with small cell lung cancer had a complete response, while one
      patient with metastatic colorectal cancer had a partial remission. Three other
      patients had stable disease, lasting between 6 and 8 months. Overall, the regimen
      was well tolerated. A phase II study using a dose of 5FU at 375 mg/m2 followed by
      topotecan at 0.75 mg/m2 intravenously over 5 days every 28 days is recommended.

PMID- 12197220
TI  - Influence of cigarette smoking on prostaglandin synthesis and cyclooxygenase-2
      gene expression in human urinary bladder cancer.
AB  - The present study examines the effect of tobacco smoking on the expression of
      cyclooxygenase (COX)-2 gene, COX enzymatic activity and prostaglandin (PG)
      synthesis in urothelial mucosal tissues from patients with bladder cancer and
      from normal individuals. The detection frequency of COX-2 mRNA was 2-fold higher
      in bladder cancer patients compared to controls and it was accompanied by a
      significantly increased COX enzymatic activity and PGE2 synthesis (p < 0.05).
      Smokers, in both control and patients groups, had higher COX-2 expression, COX
      activity, and PGE2 synthesis compared to the nonsmokers (p < 0.05). The number of
      cigarettes smoked in the cases, but not controls, correlated well with COX
      enzymatic activity (r = 0.42, p = 0.016). The observed over-expression of COX-2
      gene in human urinary bladder and the concomitant increases in PG synthesis may
      explain, at least in part, the mechanism by which cigarette smoking influences
      the development of urothelial neoplasia.

PMID- 12197221
TI  - Selective induction of colon cancer cell apoptosis by 5-fluorouracil in humans.
AB  - To assess the mechanism of action of 5-fluorouracil (5-FU) apoptosis (AI) and
      proliferation (PI) indices were determined histochemically in colon carcinoma and
      normal colon tissue of 7 patients treated preoperatively with 5-FU (300 mg/m2/day
      for 5 days) and 11 controls. 5-Fluorouracil induced apoptosis selectively in
      malignant colonocytes (AI in 5-FU-group: 0.126 +/- 0.016 [mean +/- SEM] vs. 0.065
      +/- 0.012 in controls; P < 0.05), but not in normal colonocytes. 5-Fluorouracil
      had no effect on the PI of either normal or malignant colonocytes. 5-Fluorouracil
      induced apoptosis did not correlate with clinical outcome at 24 months. We
      conclude that 5-FU: (a) induces apoptosis selectively in colon cancer cells,
      while it spares the normal colonic mucosa, and (b) has no effect on colonocyte
      proliferation under the conditions of our protocol. This effect of 5-FU may
      contribute to its chemotherapeutic activity in human colon cancer.

PMID- 12197222
TI  - Premedication strategy for weekly paclitaxel.
AB  - PURPOSE: Dexamethasone and histamine antagonists have been employed commonly as
      premedications for prophylaxis of hypersensitivity reactions (HSRs) to
      paclitaxel. Frequent premedications for weekly administration of paclitaxel are
      associated with added side-effects and extra cost. We analyzed our experience of
      HSRs to paclitaxel administered every 3-4 weeks, and designed a treatment
      algorithm to eliminate premedications in a majority of patients receiving weekly
      paclitaxel. PATIENTS AND METHODS: The incidence of HSRs was analyzed
      retrospectively in patients who received 3-hr infusions of paclitaxel (135-225
      mg/m2) every 3-4 weeks in our institution over a period of 5 years. On the basis
      of the results of this analysis, we designed a premedication schema for patients
      receiving weekly paclitaxel, 50-90 mg/m2/week, as follows: Thirty minutes prior
      to the first weekly dose of paclitaxel, patients received intravenously (i.v.)
      dexamethasone (10 mg), diphenhydramine (25 mg), and cimetidine (300 mg). If no
      HSRs occurred, all premedications were deleted for subsequent weekly paclitaxel
      doses. For patients who experienced HSRs, 20 mg of dexamethasone was given orally
      12 and 6 hr prior to re-challenge with paclitaxel in addition to diphenhydramine
      and cimetidine. RESULTS: Over a period of 5 years, 358 patients received 1608 3
      hr infusions of paclitaxel (135-225 mg/m2). Hypersensitivity reactions, which
      occurred exclusively during the first cycle of paclitaxel administration, were
      observed in 14 patients. Of these 14 patients, 11 were successfully retreated
      with paclitaxel without HSRs, two had recurrent HSRs upon paclitaxel re
      challenge, and one refused further treatment. These observations indicate that
      HSRs to paclitaxel occurred in 4% of patients upon first exposure, that most of
      these patients can be retreated successfully with paclitaxel without recurrent
      HSRs, and that if no HSRs occur during the first cycle, HSRs are unlikely to
      occur with subsequent paclitaxel administration. The premedication schema was
      applied to 30 patients receiving 205 one-hr infusions of weekly paclitaxel. Using
      this premedication strategy, no HSRs have been observed during the initial or
      subsequent administration of paclitaxel. CONCLUSION: We conclude that this
      premedication strategy is feasible and worthy of further study for patients
      receiving weekly paclitaxel.

PMID- 12197223
TI  - Feasibility trial of methotrexate-paclitaxel as a second line therapy in advanced
      urothelial cancer.
AB  - To evaluate the clinical value of the concurrent use of methotrexate administered
      immediately before paclitaxel, we investigated the efficacy and toxicity of this
      two-drug combination administered as palliative second line therapy in patients
      with advanced urothelial cancer. The design of the schedule and sequence used was
      based on our previous preclinical data from a comparative study on sequential
      combinations of paclitaxel and methotrexate in a human bladder cancer cell line.
      As a confirmation study, we further extended our analysis of in vitro synergism.
      Twenty patients with advanced transitional cell carcinoma of the urinary tract
      previously treated with platinum-based therapy, with adequate renal function and
      a performance status > or = 60 were considered eligible. They received therapy
      with methotrexate 30 mg/m2 administered as an intravenous bolus, followed
      immediately by paclitaxel 175 mg/m2 given as a 3-hr infusion, both on day 1 every
      21 days. Therapy was given on a compassionate-use basis until either disease
      progression was documented or the patient became intolerant to therapy. In vitro
      data were further analyzed using the median-effect principle and the combination
      index method. Twenty patients with metastatic (16 patients) or locally advanced
      disease (four patients) received a median of three cycles of therapy. Of the 19
      patients assessable for response, there were six partial responses and seven
      disease stabilizations with no complete responses. Median duration of response
      was 3 months (range, 2-7) and median survival was 5 months. Three patients
      developed grade 3-4 neutropenia, one patient had grade 3 anemia, four patients
      had grade 2-3 sensory neuropathy, and three patients had myalgias. Eighteen
      patients developed alopecia. Gastrointestinal toxicity was mild. One patient died
      after the first cycle due to pulmonary thrombo-embolism and could not be
      evaluated for response. The synergistic in vitro effect of the concurrent
      combination was confirmed in analyses performed under mutually exclusive and
      mutually nonexclusive criteria. In conclusion, the combination of methotrexate
      and paclitaxel at this dose and sequence is feasible and active as a palliative
      therapy in patients with advanced urothelial cancer previously treated with
      platinum-based therapies. This schedule merits further investigation in a phase
      II trial.

PMID- 12197224
TI  - Aberrant p53 staining does not predict cisplatin resistance in locally advanced
      non-small cell lung cancer.
AB  - Cisplatin based chemotherapies have increased the survival in nonsmall cell lung
      cancer. A mechanism for identifying tumors resistant to cisplatin would be useful
      in avoiding unnecessary toxicity of platinum regimens. Mutation of p53 has been
      shown to induce chemotherapy resistance in vitro. We hypothesized that tumors
      staining for p53 would be resistant to cisplatin. In Cancer and Leukemia Group B
      protocol 8935, patients with stage IIIA (N2 node positive) nonsmall cell lung
      cancer received chemotherapy followed by surgery, then post-operative
      chemotherapy and/or radiation. All patients underwent pre-treatment staging
      mediastinoscopy. Twenty-five out of forty-nine pre-treatment mediastinal lymph
      node specimens stained positively for p53. Positive staining did not correlate
      with response to chemotherapy or survival. It did predict a slightly higher
      complete or partial resection rate compared to negative staining (76 vs. 45%) (p
      = 0.042). A trend toward longer median survivals was seen in patients with
      positive p53 staining. This study does not support the ability of p53 staining to
      predict chemotherapy resistance.

PMID- 12197225
TI  - Phase II trial of pegylated-liposomal doxorubicin (Doxil) in mesothelioma.
AB  - Pegylated-liposomal doxorubicin (Doxil) is a form of liposomal doxorubicin in
      which the liposomes are coated with methoxypoly(ethylene glycol), resulting in a
      diminished uptake by the reticuloendothelial system, a longer half-life in blood,
      and a different toxicity profile than nonpegylated liposomes. A phase II study of
      Doxil in mesothelioma was performed. The initial dose per course was 55 mg/m2
      every 4 weeks with dose modification based on mucositis and hand-foot syndrome
      (the main limiting toxicities). Treatment was generally well tolerated. Of 73
      evaluable treatment courses in 15 patients, toxicities were mild and similar to
      previous reports, but dose reduction was common. No definite cardiac toxicity was
      observed. Fourteen patients were evaluable for response; four of the 15 patients
      treated responded meaningfully. These data suggest that pegylated-liposomal
      doxorubicin has activity in mesothelioma, and that this treatment is associated
      with modest toxicity.

PMID- 12197226
TI  - Frequency of proliferation, apoptosis, and their ratio during rat colon
      carcinogenesis and their characteristic pattern in the dimethylhydrazine-induced
      colon adenoma and carcinoma.
AB  - The imbalance between the cell proliferation and cell loss plays a crucial role
      in the carcinogenesis and tumor progression. However, the direction of these
      changes is still the matter of discussion. Thus, the aim of this study was to
      evaluate the proliferative activity, apoptotic activity, and
      proliferation/apoptosis ratio (P/A) assessed every 6 weeks in the colonic
      epithelium during 21 weeks of dimethylhydrazine (DMH) treatment in male Wistar
      rats. Moreover, it is necessary to answer the question whether these analyzed
      parameters correlate with the grade of differentiation or dysplasia of the
      induced tumors. It was found that DMH administration enhanced the proliferation
      in week 12 and 18 when compared with week 6. The proliferation in the control
      group did not change during the study. Up to week 12 of the experiment, there
      were no statistically significant differences between proliferative activity in
      the control and DMH-treated groups. In week 18, the proliferation in DMH-treated
      group was higher than in the control group. At all time points of the study, the
      apoptotic activity in the DMH-treated groups was significantly higher than in
      controls and in both groups, they dropped during the study. In the control group,
      apoptotic activity decreased in week 18 and was lower in comparison to that in
      week 6 and 12. In the group treated with DMH, apoptosis dropped at week 12 and
      was lower than in week 6. The P/A ratio did not change during the study in the
      control group, but increased in the DMH-treated group. After 21 weeks of DMH
      administration, 28 cases of colon adenocarcinoma and nine cases of colon adenoma
      were obtained and classified according to the WHO classification (1989) for human
      colon tumors. The adenocarcinomas were divided into four groups: well,
      moderately, poorly differentiated, and signet-ring cell carcinoma. The colon
      adenomas were divided into three groups: adenoma with mild, moderate, and severe
      grade of dysplasia. The proliferative activity in signet-ring cell carcinoma was
      significantly smaller than in well, moderately, and poorly differentiated
      adenocarcinoma and apoptotic activity was smaller than in well-differentiated
      adenocarcinoma. A weak (statistically nonsignificant) negative correlation was
      also observed between the proliferative and apoptotic activity in adenocarcinoma
      or adenoma and their grade of dedifferentiation or dysplasia, respectively.

PMID- 12197228
TI  - Fluorine-18 FDG-PET in detecting local recurrence and distant metastases in
      breast cancer--Taiwanese experiences.
AB  - Fluorine-18 fluorodeonyglucose positron emission tomography (FDG-PET) was used to
      detect local recurrence, axillary lymph node (LN) involvement and distant
      metastases in patients with breast cancer. Thirty-six female patients with breast
      cancer s/p operation underwent FDG-PET studies. Findings were confirmed by
      histology following surgery and/or biopsy or negative follow-up results over a
      period of at least one year. In the evaluation of local recurrence, the
      diagnostic sensitivity, specificity, and accuracy of FDG-PET was 100, 96.8, and
      97.2%, respectively. In the evaluation of axillary LN involvement, sensitivity,
      specificity, and accuracy was 80, 100, and 97.2%, respectively. In the evaluation
      of distant metastases, the diagnostic sensitivity, specificity, and accuracy was
      83.3, 85.2, and 84.4%, respectively. The FDG-PET is a useful diagnostic tool in
      detecting local recurrence, axillary LN involvement, and distant metastasis.

PMID- 12197227
TI  - Evaluation of the epidoxorubicin--formaldehyde conjugate, epidoxoform, in a mouse
      mammary carcinoma model.
AB  - This study was conducted to evaluate the toxicity and efficacy of Epidoxoform, a
      prodrug of the active metabolite of epidoxorubicin, in a mouse model of mammary
      carcinoma. A dose escalation trial established a maximal tolerated dose of 20
      mg/kg given intraperitoneally (i.p.) to 6-8 week old female C3 HeJ mice. Two days
      following injection of 10(6) Gollin-B mouse mammary tumor cells into the mammary
      fat pad, Epidoxoform was given and tumor growth compared to mice treated
      similarly with the maximum tolerated dose of epidoxorubicin and untreated
      controls. In all efficacy trials, a significant difference was found for tumor
      volume between Epidoxoform and epidoxorubicin treated mice and controls. In mice
      treated with a two-dose regimen, significantly increased efficacy was also found
      between Epidoxoform compared to epidoxorubicin. Epidoxoform appears to be
      efficacious in this model of mammary carcinoma, with improved efficacy over the
      parent compound epidoxorubicin. Further evaluation of this analogue appears
      warranted.

PMID- 12197229
TI  - Bcl-2 and androgen receptor gene expression in androgen-independent subclone
      derived from mouse androgen-dependent cells.
AB  - We investigated bcl-2 and androgen receptor (AR) expression in an androgen
      independent subline derived from mouse androgen-dependent mammary carcinoma
      cells. The androgen-independent SCAI cells were subcloned by cultivating androgen
      dependent SC2G cells in serum-free, androgen-free conditions. The growth of the
      SCAI cells was not affected by testosterone. Western blot analysis showed greater
      expression of Bcl-2 protein in SCAI cells than in SC2G cells. A four-day culture
      with 4 microM antisense oligonucleotide complementary to mouse bcl-2
      significantly decreased the viability of SCAI cells, when compared with sense
      control. The amount of the AR-mRNA expression in SCAI cells was slightly weaker.
      Direct sequence analysis showed no mutations in the AR of either androgen
      dependent or -independent cells. These data indicate that the increased
      expression of Bcl-2 protein plays an important role in acquiring tolerance for
      the testosterone ablation, although it is not related to AR gene alteration.

PMID- 12197230
TI  - Apoptosis in lymphocytic leukemias and lymphomas.
AB  - Most current classifications of lymphoid neoplasms define the tumors based on the
      cell of origin, phenotype, genetic abnormalities, and clinical features. Here it
      is proposed that human lymphocytic tumors can be categorized based on the
      propensity and capacity of the tumor cells to undergo apoptosis. The first
      category is defined by malignant cells that are resistant to apoptosis due to
      expression of anti-apoptotic factors such as bcl-2 and cellular inhibitors of
      apoptosis (IAPs). These tumors would include CLL and follicular lymphomas, as
      well as some malignancies in which the tumor cells are infected by viruses that
      co-opt cell survival pathways, such as human T-cell leukemia/lymphoma virus
      (HTLV)-1. The second category, in which the malignant cells are apoptosis-prone,
      would include tumors arising in the context of impaired cytotoxic T-cell
      function. These neoplasms would include some human immunodeficiency virus (HIV)
      related lymphomas such as Burkitt's lymphoma, and post-transplantation lymphomas.
      The third category would include neoplasms of intermediate sensitivity to
      apoptosis, some of which are associated with infection such as mucosa-associated
      lymphoid tissue (MALT) lymphomas of the stomach. Although this classification is
      tentative, it should evolve in parallel with our understanding of pathogenic
      mechanisms in lymphoid neoplasia, and provides a novel framework with which to
      consider the appropriateness of specific therapeutic strategies. Distinctions
      among lymphocytic tumors in terms of the likelihood of response to therapies such
      as antisense to bcl-2 related proteins, inhibitors of NF-kappa B activity, and
      new approaches aimed at bolstering the host's immune response, would cross
      standard classifications based on the T or B-cell origin of the tumor cells.

PMID- 12197231
TI  - Primary splenic lymphoma: report of 10 cases using the REAL classification.
AB  - Primary splenic lymphoma (PSL) is rare with a reported incidence of less than 1%.
      Diffuse large cell pathology has been reported in 22-33% of the cases and is felt
      to have a poor outcome. We report our experience in patients with PSL seen at
      Mount Sinai Medical Center during the years 1994-1999. Our objective was to
      evaluate staging (using the Ahmann and Kehoe criteria), prognosis using the
      International Prognostic Index (IPI), and pathology using the Revised European
      American Lymphoma Classification (REAL) classification. Ten patients were
      identified. Eight of the 10 patients had diffuse large cell lymphoma (DLCL).
      Using the IPI, four patients were categorized as low risk, three as
      low/intermediate risk, and three as high risk. The only two deaths occurred in
      the high-risk group. Lymph node involvement beyond the splenic hilum seen by
      imaging studies represents an advanced non-Hodgkin's lymphoma and should be
      included no longer in the staging of PSL. Nine of the 10 underwent a splenectomy.
      Eight of the nine patients received chemotherapy following splenectomy. Seven of
      the nine patients remained in remission from 1 to 19 years. Splenectomy followed
      by combination chemotherapy, results in excellent long-term survival in PSL.

PMID- 12197233
TI  - Therapy of melanoma with allogeneic melanoma lysates alone or with interferon
      alfa.

PMID- 12197232
TI  - Embolization of uterine artery in terminal stage cervical cancers.
AB  - Ligation of the hypogastric artery has been a standard and effective procedure in
      controlling massive bleeding in advanced cervical carcinoma. The authors wanted
      to demonstrate the selective use of embolization of hypogastric or uterine artery
      to achieve the same end result--the stoppage of vaginal bleeding. In a number of
      cases, surgical approach may not be appropriate either because of the critically
      ill patient or because of the highly deformed pelvic anatomy due to radiotherapy
      or to the recurrence of cancerous tissue. As an alternative therapy, we used
      selective embolization of the uterine artery in eight patients. In all the
      patients, embolization served to control bleeding. As the bleeding was brought
      under control, a gradual recovery of the patient was generally observed. The most
      common side-effect was temporary severe pain related to ischemia of tumoral
      tissue. Embolization may be regarded as an effective procedure, which can be used
      to control massive bleeding in selected cervical cancer patients.

PMID- 12197234
TI  - Cervical intraepithelial neoplasia: an overview of diagnosis and management.

PMID- 12197235
TI  - Diagnostic workup of neoplastic lesions in the cirrhotic liver: the case for
      minimizing invasive diagnostic studies.

PMID- 12197236
TI  - The development of aggressive cancer: a possible role for sphingolipids.

PMID- 12197237
TI  - Organization, function, and accomplishments of the Gynecologic Oncology Group.

PMID- 12197239
TI  - Local treatment of brain tumors with targeted chimera cytotoxic proteins.
AB  - High-grade astrocytomas (HGA) are the most prevalent brain tumors that represent
      a unique pharmaceutical challenge. Their cerebral localization and characteristic
      features of tumor progression primarily dictate this challenge. Targeted chimera
      conjugate/fusion cytotoxic proteins have become the newest class of investigative
      drug candidates for the treatment of HGA due to their inherent properties that
      are compatible with drug deliveries to brain tumors. A conjugate of a human
      transferrin with bacterial toxin, Diphtheria toxin, has shown clinical efficacy
      in Phase I and II trials when administered intratumorally through convection
      enhanced delivery. This immunotoxin belongs to the first group of immunotoxins
      that started to live up to early expectations. Other anti-brain tumor cytotoxins
      have entered or will enter the clinic shortly. The clinical applicability of
      targeted bacterial toxin-containing cytotoxins in the treatment of brain tumors
      warrants further development and careful clinical evaluation.

PMID- 12197238
TI  - Defining clinically meaningful outcomes in the evaluation of new treatments for
      oral mucositis: oral mucositis patient provider advisory board.
AB  - Oral mucositis (OM)-related outcomes constituting a meaningful clinical advance
      in bone marrow transplant patients were considered by an interdisciplinary panel.
      Meaningful outcomes are essential in product development for OM, a condition
      without effective prevention or treatment. The most important outcomes to
      measure, the feasibility of measuring these in a clinical trial, and clinically
      meaningful differences in these outcomes were determined by the panel. Most
      important are reduction in oral pain and use of opioid analgesics, improvement in
      oral intake and quality of life, and reduction of hospitalization duration.
      Reduction in the severity of OM measured by an objective evaluation of oral
      mucosa could provide insight regarding the biologic activity of an intervention.
      Further data are required to define the precise relationship between reduction in
      visible OM and improvement in outcome. Minimally, clinical trials for OM should
      assess oral pain, opioid use, oral intake, and include objective assessment of
      OM.

PMID- 12197240
TI  - Multidisciplinary management of soft-tissue sarcomas.

PMID- 12197241
TI  - Chemokines and cancer.

PMID- 12197242
TI  - Thalidomide: an old drug with new clinical applications.

PMID- 12197243
TI  - Estramustine plus a taxane for advanced prostate cancer: the new standard
      therapy?

PMID- 12197244
TI  - Defining clinically meaningful outcomes in the evaluation of new treatments for
      oral mucositis: a commentary.

PMID- 12197245
TI  - GIST 1, chemotherapy 0, with a brand new hitter up next.

PMID- 12197246
TI  - Salvage therapy for platinum-refractory urothelial cancer: designing new clinical
      trials.

PMID- 12197247
TI  - Chemokines: small, but powerful regulators of the immune system--potential anti
      tumor targets and reagents.

PMID- 12197248
TI  - Stable disease in mesothelioma: a therapeutic achievement?

PMID- 12197249
TI  - Frontline--writing psychoanalytic case reports: safeguarding privacy while
      preserving integrity.

PMID- 12197250
TI  - Mortal gifts: a two-part essay on the therapist's mortality. Part I: untimely
      loss.
AB  - The absence of theoretical and practical provisions for the patient whose
      therapist dies or becomes seriously ill reflects underlying problems regarding
      termination. Therapy is unique among human intimacies in that its goal is
      separation, a paradox that informs both the near-silence of early termination
      theory and the confusion in more recent writing. The therapist's emotional
      involvement must be understood through the therapeutic relationship as part of
      "mortal" life, that is, as a specialized category within ordinary human
      interactions. The profession has neglected the therapist's mortality, in
      figurative as well as literal senses. This neglect, a covert grandiosity, is the
      "Olympian Delusion." On one level, inadequate termination theory underlines
      failure to confront the therapist's mortality; more profoundly, failure to
      confront the therapist's mortality underlies deficiencies in termination theory.
      The mystique of the superhuman therapist can lead to a professional reticence
      that is less than fully human, abrogating the patient's right to a decent, human
      leave taking.

PMID- 12197252
TI  - Historicity, humility, and the analytic exercise reply to commentaries by Drs.
      Palombo and Horner.

PMID- 12197251
TI  - Behind, beneath, above, and beyond: the historical unconscious.
AB  - The unconscious is more than a collection of intrapsychic and interpersonal
      variables. On a broader level, it reflects a complex, historically woven tapestry
      of moral and ethical values, beliefs, and assumptions. A particular historical
      context provides an experiential and interpretive template that conditions the
      boundary between what is conscious and unconscious. Beyond the scope of
      explicitly inherited values, beliefs, and assumptions is what the historical
      unconscious comprises. It lingers at the very edge of our conscious experience,
      behind, beneath, above, and beyond everything that is spoken or unspoken, enacted
      or restrained, imagined or suppressed.

PMID- 12197253
TI  - Primal scene derivatives in the work of Yukio Mishima: the primal scene fantasy.
AB  - This article discusses the preoccupation with fire, revenge, crucifixion, and
      other fantasies as they relate to the primal scene. The manifestations of these
      fantasies are demonstrated in a work of fiction by Yukio Mishima. The Temple of
      the Golden Pavillion. As is the case in other writings of Mishima there is a
      fusion of aggressive and libidinal drives and a preoccupation with death. The
      primal scene is directly connected with pyromania and destructive "acting out" of
      fantasies. This article is timely with regard to understanding contemporary
      events of cultural and national destruction.

PMID- 12197254
TI  - Afterword to Krazy: George Herriman's Krazy Kat cartoon and its appeal to E. E.
      Cummings.
AB  - George Herriman's "Krazy Kat," a linguistically innovative and trenchant comic
      strip that appeared in newspapers from 1916-1944, attracted the attention of our
      major American poet, e. e. cummings, who wrote a foreword to a collection of the
      strips and admired it for its transcendent celebration of love over egoism in a
      triadic relationship, its scorn of politics, and its brick-throwing irreverence.
      Similarities between Cummings's and Herriman's work include language play,
      humorous voices, examinations of dimensions of empathy and theory of mind,
      musicality, and humanistic religiosity.

PMID- 12197255
TI  - Psychoanalytic peregrinations. II: Psychoanalysis as science and art.
AB  - The foundations of psychoanalytic clinical practice involve the role of fantasy,
      creativity, and imagination as well as the natural science aspects of
      psychoanalysis. There is a common ground for psychoanalytic technique and we
      should not in a "politically correct" manner, as is so popular today, abandon the
      philosophical or Platonic foundationalism that lies at the basis of Freud's
      psychoanalytic practices. Although it is a "politically incorrect" view, a
      reasonable degree of objectivity and scientific validity is attainable by the
      relatively neutral psychoanalyst, using both natural science observations as well
      as introspection and hermeneutics. Furthermore, since psychoanalysis is
      fundamentally a creative activity, the roots of creativity require exploration
      and careful study. Subjective and first person methodologies such as Freud's
      psychoanalysis and phenomenology cannot be ignored in our search for the core of
      the self of each of our patients.

PMID- 12197256
TI  - Revisiting Fromm's passions as presaging contemporary views of affect and
      dissociation.
AB  - Fromm viewed intrapsychic dynamic processes as having their origin in a
      generalized organic life force that gets transformed into psychic energy called
      passions. He is acknowledged as one of the most original, creative writers of the
      mid-20th century whose fertile mind and humanistic sensibilities synthesized the
      domains of psychoanalysis, social philosophy, and politics. His unyielding belief
      that the development of the individual psyche is inseparable from its two-way
      interaction with a lived relational and cultural context presaged the evolution
      of the relational perspective in psychoanalysis, and his concept of passions
      foreshadowed contemporary neuroscientific theories of affect and its role in
      intrapsychic life and self-identity formation. Damasio's theory of emotions is
      reviewed as a specific example of the current revamping of psychoanalytic theory
      as bottom-up information processing, that is, the integrating and synthesizing of
      affective experience and memory (preverbal mentalization) as fueling the creation
      of a narrative self. Fromm's discussions of dissociation are linked both to
      Damasio's core self experiences and to Bromberg's conceptualization of
      psychoanalysis of dissociative experience as a process of "standing in the
      spaces." And finally, Fromm's descriptions of psychoanalysis as an art are linked
      to Schon's action-oriented theory of practical knowledge.

PMID- 12197257
TI  - Heroin addiction: the needle as transitional object.
AB  - The etiology of heroin addiction is examined from the perspective of object
      relations, one psychoanalytic model among many that can offer fruitful
      understanding. Material is drawn from the literature and from a case example. The
      major specific focus is on the needle as a transitional object in patients who
      have experienced early childhood deprivation and separation trauma.

PMID- 12197258
TI  - Lupus cerebritis: a case study.
AB  - Nervous system involvement in systemic lupus erythematosus (SLE) occurs in 24%
      50% of all patients in the United States at some time during the course of their
      illness. Lupus cerebritis with associated headache, seizures, stroke, and chorea
      is just one of a wide array of central nervous system disorders SLE patients can
      develop. It also is one of the most difficult manifestations of lupus to
      diagnose. Advances in imaging and laboratory analysis have contributed to an
      earlier and more specific diagnosis of lupus cerebritis. Despite improvements in
      the ability to treat SLE, management of nervous system manifestations remains
      unsatisfactory. Controversy exists as to the best approach for treatment. Newer
      combination therapies based on anecdotal evidence are suggested.

PMID- 12197259
TI  - Predictors of burden for caregivers of patients with Parkinson's disease.
AB  - Parkinson's disease (PD) is a chronic, progressive neurological disease that
      affects an estimated 1 million Americans each year. Its progressive nature leads
      to increased burden for the caregiver. This study explored factors that
      contribute to the perception of burden in caregivers of individuals with PD using
      a cross-sectional design. The sample consisted of 41 caregivers who were married
      to or cohabitating with individuals with PD. Questionnaires were mailed to
      spousal caregivers and returned via mail. Burden was determined by utilizing the
      Zarit Burden Inventory. The independent variables that were measured were
      activities of daily living (ADLs), perceived social support, psychological well
      being, and marital satisfaction. All four factors were found to significantly
      predict perceived burden. Multiple regression analysis showed that ADLs and
      perceived social support were significant predictors of caregiver burden,
      accounting for 44.3% of the variance. The implication for healthcare
      professionals is that they should provide information on PD symptom management,
      thus promoting independence in performing ADLs, identifying appropriate resources
      to reduce caregiver burden, and using support groups.

PMID- 12197260
TI  - A descriptive study of cognitive status in acute motor stroke.
AB  - Stroke, or brain attack, is the third leading cause of death in the United States
      and a leading cause of disability in the rapidly aging population. Cognitive
      status after one particular type of brain attack, motor stroke, has received
      minimal attention. Intact cognition assists in recovery following stroke;
      therefore, cognitive status is of great interest to clinicians and researchers.
      The purpose of this study, part of a larger study of functional recovery
      following motor stroke, was to describe the cognitive status of 100 patients
      during the acute phase of care. Cognitive status was measured using two
      instruments: the Mini-Mental State Examination and the Neurobehavioral Cognitive
      Status Examination (NCSE). This study provides a rich description of the
      cognitive status of a group of individuals who suffered a motor stroke.
      Clinicians, including neuroscience nurses, need to use appropriate tools (such as
      the NCSE) to assess for and address specific cognitive deficits in the areas of
      memory and constructional ability and to recognize similarities following motor
      stroke.

PMID- 12197261
TI  - Central neurocytoma: a case study.
AB  - Central neurocytoma (CN) is a rare intraventricular brain tumor that affects
      young adults. Just over 100 cases of CN have been reported since it was first
      described in 1982. It accounts for less than 1% of all central nervous system
      neoplasms. It is characterized by cystic spaces and intratumoral calcification.
      The tumor is generally hypervascular. Patients generally present with signs and
      symptoms of noncommunicating hydrocephalus such as headache, visual disturbances
      such as blurry vision and visual field deficit, and nausea or vomiting or both.
      Gross total surgical resection is the treatment of choice for CN. Other treatment
      modalities such as radiation therapy, radiosurgery, and chemotherapy may offer
      adjunctive or alternative treatment for residual or recurrent CN. The clinical
      outcome is generally good.

PMID- 12197262
TI  - Double-blind, randomized, controlled trial of local anesthetic use for iliac
      crest donor site pain.
AB  - Autogenous iliac crest bone grafts are often used for persons undergoing anterior
      cervical fusion (ACF). Study findings have shown that pain at the iliac crest
      donor site can often be more severe than that at the primary operation site. A
      method used to eliminate pain after bone harvesting involves infiltration of a
      local anesthetic directly into the site. This study examined the efficacy of
      local anesthetic infiltration in the control of donor site pain, utilizing a
      randomized, double-blind, placebo-conrolled design. All participants received
      standard postoperative intravenous and oral analgesic. Those in the study group
      also received six injections of bupivacaine hydrochloride 0.25% into the donor
      site, while participants in the placebo group received normal saline injections.
      Participants receiving bupivacaine (n = 14) consistently reported lower hip pain
      scores than participants receiving the placebo (n = 8), with significant
      differences noted 3 hours after the first and second doses of the study drug. The
      bupivacaine group's mean morphine intake for the first 24 hours after surgery was
      found to be lower (32 mg; placebo 44 mg), whereas participants younger than 49
      years who received bupivacaine were found, on average, to have stayed in the
      hospital one day less (3.6 days) than placebo group participants (4.5 days).
      Younger participants receiving bupivacaine required less morphine and had, on
      average, a reduced length of stay. The clinical implication of using local
      anesthetic for the relief of donor site pain suggests that it is a safe and
      efficacious technique.

PMID- 12197263
TI  - Issues of consent and data collection in vulnerable populations.

PMID- 12197264
TI  - Mercury exposure and early effects: an overview.
AB  - OBJECTIVES: This paper was given as a keynote address at the conference on The
      Assessment of the Effects Due to Low Doses of Inorganic Mercury following
      Environmental and Occupational Exposures: Human and in vitro Studies on the
      Specific Mechanisms of Toxicity in Gargnano, Italy, in September 2001. METHODS:
      The most relevant literature over the past 40 years has been reviewed, and in
      particular, the proceedings of the World Health Organisation conferences on the
      health effects of inorganic and organic mercury exposure have been considered.
      RESULTS: In an uncontaminated environment the general population is exposed to
      mercury vapour from the atmosphere and from dental amalgam, while the diet,
      mainly from fish, is the principal source for methyl mercury absorption. Mercury
      vapour release from amalgam fillings increases with chewing, with absorption and
      uptake by the brain and kidneys. Infants exposed to phenyl mercury from treated
      diapers and young children ingesting mercurous chloride in teething powders have
      developed acrodynia (pink disease), and Kawasaki disease and the use of mercurial
      skin lightening creams has been followed by the development of the nephrotic
      syndrome. Both mercury compounds and mercury vapour have given rise to contact
      dermatitis in the general population. Epidemics of mercury poisoning have
      followed release of mercury into the environment from industrial activity, with
      uptake of methyl mercury from fish eating in Minamata Bay and uptake of both
      inorganic and methyl mercury following release of mercury vapour and deposition
      into waterways from gold recovery procedures in the Amazon basin. The ingestion
      of wheat and barley seed treated with an alkyl mercury fungicide for sowing, by a
      largely illiterate population in Iraq, led to a major outbreak of poisoning with
      a high fatality rate. Following exposure to mercury vapour, the earliest
      clinically observed adverse effects at urine mercury levels of the order of 30
      100 mg/g creatinine, are objectively detectable tremor, psychological disorder
      and impaired nerve conduction velocity in sensitive subjects, with subjective
      symptoms of irritability, fatigue and anorexia. At these and at lower levels,
      proteinuria has also been observed. Both glomerular and tubular damage may occur
      at exposure levels lower than those giving rise to central nervous system
      effects. An immunological effect has also been observed in studies on clinically
      asymptomatic workers with low level exposure. CONCLUSIONS: As mercury can give
      rise to allergic and immunotoxic reactions which may be genetically regulated, in
      the absence of adequate dose-response studies for immunologically sensitive
      individuals, it has not been possible to set a level for mercury in blood or
      urine below which mercury related symptoms will not occur.

PMID- 12197265
TI  - [Introduction: scope and purpose of the multicenter project " Assessment of
      effects due to low doses in inorganic mercury following environmental and
      occupational exposure: human and in vitro studies on specific toxicity
      mechanisms"].
AB  - The principal aims of the project financed by the Italian Ministry of University
      and Scientific and Technological Research were: to verify if at the current limit
      values early biological effects can be demonstrated; to identify the levels of
      internal dose that can cause early effects; to evaluate the non-occupational
      factors that can contribute to the levels of internal dose. In particular, the
      mercury intake derived from dental amalgams and fish consumption was considered.
      The internal dose was measured with the traditional biological indicators
      (urinary and blood mercury) and with the speciation of a large percentage of
      biological samples by ICP-MS. The central nervous system, neuroendocrine
      function, kidney and the immune system were considered as target organs and were
      examined using previously standardized indicators of effects. Two groups of
      subjects were included in the study: workers with occupational exposure to
      inorganic mercury in different industrial settings and control subjects
      identified from the general population. The first group was characterized by an
      exposure level to inorganic mercury clearly below the current limit values;
      whereas the HgU levels of a relevant number of control subjects were similar to
      those measured in the exposed subjects. The in vitro studies covered several
      issues: the percutaneous absorption of mercury using skin derived from human post
      mortem samples in a standardized model; the release of the metal from dental
      amalgams in different physiological conditions of the oral cavity; the effects of
      increasing doses of mercury chloride on tubular renal cells. The project was
      realized with the cooperation of seven Research Units from six Italian
      Universities. Researchers belonging to Departments of Occupational Medicine,
      Industrial Hygiene, General Pathology, Biochemistry, Odontology, and
      Biostatistics were involved to achieve a multidisciplinary approach. The results
      of this research project are described and discussed in the following papers.

PMID- 12197267
TI  - [Urinary and blood markers of internal mercury dose in workers from a chlorakali
      plant and in subjects not occupationally exposed: relation to dental amalgam and
      fish consumption].
AB  - OBJECTIVES: The aim of this paper was both to evaluate the internal dose of Hg in
      occupationally exposed workers (35 Chloralkali workers) compared to that of non
      occupationally exposed controls (40 workers of the same plant of Portotorres and
      22 residents on the island of Carloforte, usual consumers of local fish, mostly
      tuna fish with relatively high Hg levels) and to assess the relevance of
      environmental and individual exposure factors linked to lifestyle, sea fish
      consumption and amalgam fillings. METHODS: All subjects filled out a
      questionnaire concerning the working history and lifestyle. The amalgam fillings
      area was measured by medical inspection using a standardised schedule attached to
      the questionnaire. Mercury in urine (HgU) was measured in all cases, while in a
      subgroup of our study total blood mercury (HgB) and its organic and inorganic
      component were also assessed. Furthermore, for 8 of the Carloforte group mercury
      in hair was also available. RESULTS: Values of urinary mercury excretion of the
      Chloralkali workers were significantly higher (median value of 15.4, range 4.8
      35.0 micrograms/g creatinine, 94.3% of the cases having values > 5 micrograms/g
      creatinine) than those observed both among the reference group (median value of
      1.9, range 0.4-5.6 micrograms/g creatinine, 12.5% of the cases having values a
      little greater than 5 micrograms/g creatinine) and among the residents in
      Carloforte (median value of 6.5, range 1.8-21.5 micrograms/g creatinine, 59.1% of
      the cases having values > 5 mcg/g creatinine). The HgU values observed in this
      group were in turn significantly higher than those of the non occupationally
      exposed workers living near Sassari (p = 0.03). Only in this last group were the
      HgU concentrations statistically significantly related to the extension of the
      amalgam fillings area (Pearson r = 0.53, p < 0.01). In the Carloforte group HgU
      was significantly related to the number of fish meal consumed per week (Pearson r
      = 0.48, p < 0.02). HgB (median value of 5.9, range 3.4-21.6 micrograms/l) as well
      as its inorganic component (median value of 2.4, range 1.8-4.6 micrograms/l) were
      significantly higher in the Chloralkali group compared to the other two groups.
      In all cases of the Carloforte group the ratio between the organic component and
      the total HgB was higher than 85%, while this ratio was significantly lower in
      the other two groups. The relationship between HgU and HgB was statistically
      significant, considering both total blood mercury and the inorganic and the
      organic components separately. A statistically significant relationship between
      the sea fish consumption per week and both total HgB (Pearson r = 0.82) and the
      organic component in this matrix (Pearson r = 0.84, p < 0.001) was observed among
      16 non-occupationally exposed subjects. However, the significant relationship
      between organic blood mercury and sea fish consumption was almost entirely
      supported by the data observed in the Carloforte group. Total hair mercury levels
      analysed in 8 subjects of the Carloforte group were high (median value of 9.6,
      range 1.4-34.5 micrograms/g) and significantly related to sea fish consumption,
      and to both the individual Hg urinary excretion (Pearson r = 0.83) and to the
      organic component of blood mercury (Pearson r = 0.87). CONCLUSIONS: According to
      several experimental human and animal trials and to some recent studies on
      methylmercury toxicokinetic models, our results suggest that the organic
      compounds absorbed by usual sea fish consumption may be partially demethylated,
      increasing the inorganic Hg concentration in the kidney and consequently its
      urinary excretion, as was observed in the Carloforte group.

PMID- 12197266
TI  - [Evaluation of the dose of mercury in exposed and control subjects].
AB  - OBJECTIVES: The aim of this paper was to analyse the concentrations of HgU and
      HgB in three different groups: 122 workers exposed, 18 workers formerly exposed
      and 196 subjects not occupationally or environmentally exposed to mercury.
      METHODS: All the subjects filled out a questionnaire concerning personal data,
      lifestyle, occupational or non-occupational exposure to Hg and medical history.
      The amalgam fillings area was measured by a standardised method. RESULTS: Urinary
      mercury excretion was significantly greater in the group of the exposed workers
      respect to the group of subjects not occupationally exposed (Median value of 8.3
      micrograms/g creatinine and the 5 degrees and 95 degrees percentile respectively
      of 2.66 e 23.50 micrograms/g creatinine against Median value of 1.2 micrograms/g
      creatinine and the 5 degrees and 95 degrees percentile respectively of 0.18 and
      5.42 micrograms/g creatinine). U-Hg in formerly exposed workers were comparable
      to U-Hg in non-occupationally exposed subjects, with a median value of 1.6
      micrograms/g creatinine. B-Hg values were similar in the three groups: the median
      value was 3.1 micrograms/l in the non-occupationally exposed, 4.0 micrograms/l in
      the exposed workers and 3.9 micrograms/l in the past exposed. These value were
      not significantly different. Among the considered variables (amalgam fillings,
      fish consumption, age, sex, alcohol intake, chewing-gum and smoking) dental
      amalgam and fish consumption were significantly related with the Hg urinary
      excretion and the B-Hg levels. This is particularly true considering the subjects
      altogether: for the exposed workers, indeed, the occupational exposure was the
      most relevant variable. CONCLUSIONS: The results of the present research
      confirmed that the U-Hg excretion in non-occupationally exposed subjects is
      influenced by amalgam dental fillings. Furthermore, in our study Hg urinary
      excretion was significantly related with fish consumption. This fact can be
      explained, according to several recent experimental human and animal trials,
      considering that methylmercury contained in fish is partially converted, through
      breakage of the carbon-Hg bond, into Hg inorganic forms, which accumulate in the
      kidney and have a urinary excretion pathway.

PMID- 12197268
TI  - [Evaluation of sources of mercury absorption through studying urinary mercury
      levels in the general population].
AB  - OBJECTIVES: The number of instances where mercury exposure is possible outside
      the workplace are numerous, with the main source being amalgam dental fillings
      and diet. It is also possible to envisage environmental exposure in subjects
      resident in areas where there is existing environmental contamination. This is
      probably what happened in Tuscany where past mining activity in the Monte Amiata
      area may have been the cause. This study estimated the concentration of urinary
      mercury (HgU) in non-occupationally exposed subjects from southern Tuscany, with
      the aim of evaluating the sources of mercury absorption in the general
      population. METHODS: A questionnaire aimed at collecting specific information on
      factors which might influence the uptake of mercury was used. 164 subjects were
      studied: 82 subjects (41 males, 41 females) came from the Monte Amiata area and
      the other 82 (41 males, 41 females) from the Province of Siena. In this way it
      was possible to evaluate the elements associated with everyday life which may
      have influenced the presence of the metal in the urine. Since the distribution of
      the variables cannot be assumed multivariate normal as usual, a recently-proposed
      method based on a permutation procedure was adopted that allows the analysis of
      the variables as well as the single marginal analyses, without assuming any model
      for the distribution of variables. RESULTS AND CONCLUSIONS: The results showed
      significantly lower levels of HgU in the subjects from the Monte Amiata area.
      Highly significant differences were demonstrated in the population which was sub
      divided according to number and surfaces of amalgam fillings, use of contact
      lenses and type of water drunk (p < 0.001). Correlations between the levels of
      HgU and the investigated variables were not observed. It was confirmed that
      mercury uptake is simultaneously influenced by many factors. Probably the
      presence of higher levels of mercury in the environment in the Monte Amiata area
      is a factor of minor importance compared to others, especially the number of
      amalgam fillings, in determining mercury absorption in the general population.

PMID- 12197269
TI  - [Renal effects of low doses of mercury].
AB  - OBJECTIVES: The present study was aimed at investigating early markers of renal
      damage and dysfunction in subjects exposed to low doses of mercury from different
      sources. Different groups of subjects were examined with urinary Hg excretion
      (HgU) ranging from 0.1 to 35.0 micrograms/g creatinine: 122 occupationally
      exposed workers, 22 subjects living in a non-polluted area, but consuming large
      amounts of tuna and sword fish, and 197 controls. METHODS: Several markers of
      renal changes were measured in urine (albumin, fibronectin, beta 2-microglobulin,
      retinol-binding protein, tubular antigens, N-acetyl-beta-D-glucosaminidase
      activity) and serum (beta 2-microglobulin and cystatin C). Serum autoantibodies
      towards collagen, laminin and tubular antigens were assessed in subjects with
      abnormal renal markers. The role of glutathione-S-tranferases GSTT1 and GSTM1
      polymorphisms in the inter-individual variability of biological response to Hg
      was also investigated. RESULTS: Renal markers were not correlated with HgU. None
      of such markers differed significantly between exposed workers and controls,
      except for urinary beta 2-microglobulin, which was decreased in Hg-exposed
      workers (GM = 55.8 vs 86.6 micrograms/g creatinine), in the absence of any
      changes in serum concentration. Subjects usually eating tuna and sword fish
      showed an increased urinary excretion of beta 2-microglobulin, albumin and
      fibronectin. Serum titres of auto-antibodies did not differ between the groups.
      Neither in controls nor in exposed workers were the observed differences modified
      by the GSTM1 and GSTT1 genotypes. CONCLUSION: The present study did not provide
      evidence of any changes in kidney integrity and function in subjects exposed to
      very low levels of inorganic Hg resulting in urinary Hg lower than 35
      micrograms/g creatinine. Nor did we obtain evidence of Hg-induced autoimmunity
      towards kidney components. The potential modifying role of GST polymorphisms
      could not be clarified in the absence of effects associated with exposure to the
      risk factor, i.e., to inorganic Hg. Preliminary data suggesting nephrotoxic
      effects of organic Hg from a diet rich in large fish resulting in increased
      levels of both blood and urinary Hg--which however did not exceed 20 micrograms/g
      creatinine--deserves further investigation.

PMID- 12197270
TI  - [Neurotoxic effect of exposure to low doses of mercury].
AB  - OBJECTIVES: To assess early effects on the Central Nervous System due to
      occupational exposure to low levels of inorganic mercury (Hg) in a multicenter
      nationwide cross-sectional study, including workers from chloro-alkali plants,
      chemical industry, thermometer and fluorescent lamp manufacturing. The
      contribution of non-occupational exposure to inorganic Hg from dental amalgams
      and to organic Hg from fish consumption was also considered. METHODS:
      Neuropsychological and neuroendocrine functions were examined in a population of
      122 workers occupationally exposed to Hg, and 196 control subjects, not
      occupationally exposed to Hg. Neuropsychological functions were assessed with
      neurobehavioral testing including vigilance, motor and cognitive function, tremor
      measurements, and with symptoms concerning neuropsychological and mood
      assessment. Neuroendocrine functions were examined with the measurement of
      prolactin secretion. The target population was also characterized by the surface
      of dental amalgams and sea fish consumption. RESULTS: In the exposed workers the
      mean urinary Hg (HgU) was 10.4 +/- 6.9 (median 8.3, geometric mean 8.3, range 0.2
      35.2) micrograms/g creatinine, whereas in the control group the mean HgU was 1.9
      +/- 2.8 (median 1.2, geometric mean 1.2, range 0.1-33.2) micrograms/g creatinine.
      The results indicated homogeneous distribution of most neurobehavioral parameters
      among exposed and controls. On the contrary, finger tapping (p < 0.01) and the
      BAMT (Branches Alternate Movement Task) coordination test (p = 0.05) were
      associated with occupational exposure, indicating an impairment in the exposed
      subjects. Prolactin levels resulted significantly decreased among the exposed
      workers, and inversely related to HgU on an individual basis (p < 0.05). An
      inverse association was also observed between most neuropsychological symptoms
      and sea fish consumption, indicating a "beneficial effect" from eating sea fish.
      On the contrary, no effects were observed as a function of dental amalgams.
      CONCLUSIONS: In conclusion, this study supports the finding of early alterations
      of motor function and neuroendocrine secretion at very low exposure levels of
      inorganic Hg, below the current ACGIH BEI and below the most recent exposure
      levels reported in the literature.

PMID- 12197271
TI  - [Neuroendocrine and neurobehavioral effects associated with exposure to low doses
      of mercury from habitual consumption of marine fish].
AB  - OBJECTIVES: To evaluate neuroendocrine and neurobehavioral effects possibly
      associated with increased dietary intake of organic mercury (Hg), a group of 22
      subjects living on the island of Carloforte (south-west Sardinia) was examined,
      who were regular consumers of tuna fish with relatively high Hg content. This
      group, never exposed occupationally to either Hg or to other neurotoxic
      substances, was compared with 22 age-matched controls employed at a chemical
      plant in Portotorres (northern Sardinia). METHODS: Hg in urine (HgU) and serum
      prolactin (PRL) were measured in all cases, whereas measurements of total (HgB)
      and organic blood mercury were available only for 10 subjects from Carloforte and
      6 controls. Data about working history and lifestyle (education, smoking habit,
      alcohol and sea fish consumption) were collected by an interviewer using a
      standardised questionnaire. Neurotoxic symptoms were evaluated by a self
      administered questionnaire, whereas a test battery, including some computerised
      tests of the Swedish Performance Evaluation System (SPES) to assess vigilance and
      psychomotor performance, some tests on motor coordination (Luria-Nebraska and
      Branches Alternate Movement Task) and one memory test for numbers (Digit Span)
      was administered to assess neurobehavioral changes associated with exposure to
      dietary intake of organic mercury. In all cases, characteristics of hand tremor
      were evaluated by the CATSYS System 7.0. RESULTS: HgU values were significantly
      higher in the Carloforte group (median 6.5, range 1.8-21.5 micrograms/g
      creatinine) compared with controls (median 1.5, range 0.5-5.3 micrograms/g
      creatinine). Serum PRL was significantly higher among subjects from Carloforte
      and correlated with both urine and blood Hg levels. The scores of each item of
      the questionnaire investigating neurological symptoms were not statistically
      different in the two groups. In some tests of the SPES battery (Color Word
      Vigilance, Digit Symbol and Finger Tapping) the performance of the Carloforte
      group was significantly worse than that of controls, whereas in the other
      neurobehavioral tests poorer performances by the Carloforte group were not
      statistically significant. None of the tremor parameters was significantly
      different comparing the two groups. Multivariate analysis--controlling for
      education level and other covariates--carried out for the Symbol-Digit Reaction
      Time and for the Branches Alternate Movement Task (BAMT) showed that organic Hg
      concentration in blood was the most significant factor negatively affecting
      individual performance in these tests. Serum PRL was correlated with some
      neurobehavioral tests (Digit Symbol, Finger Tapping and BAMT). CONCLUSIONS: Some
      of the neurobehavioral tests were sensitive enough to discriminate groups with
      different Hg body burden, even in the low-dose range. However, the pattern of
      results suggests adverse neurobehavioral effects, especially on psycho-motor
      coordination, with a significant dose-effect relationship, mostly associated with
      long-term exposure to low levels of organic mercury due to the usual consumption
      of large fish with relatively high levels of Hg in the flash.

PMID- 12197273
TI  - [Adaptation of the TriTEST TM for the investigation of blood samples for a
      multicenter study taken to a single laboratory].
AB  - BACKGROUND: Immunotoxicological studies in humans are usually carried out via the
      determination of some selected immune parameters in subjects occupationally
      and/or environmentally exposed to immunotoxic substance. One of the most often
      measured parameters is the determination of lymphocyte subsets, which needs to be
      carried out in a very short time (a few hours) after blood collection. This is
      the major problem limiting the determination of lymphocyte subpopulations in
      field studies, where samples are usually collected directly at the workplace, and
      very often at the end of the workshift. Unfortunately, these collection
      modalities significantly prolong the time between collection and analysis. The
      problem is more evident in multicentric studies, where a further problem is
      represented by the time needed to send samples to the laboratory. OBJECTIVE:
      Since an immune evaluation was planned, including the determination of lymphocyte
      subpopulations CD4 (T-helper), CD8 (T-suppressor cytotoxic) and CD16/CD56
      (natural killer) in the project "Assessing health effects in man from exposure to
      low doses of inorganic mercury in environmental and occupational settings", a
      method was developed for performing cytofluorimetric analysis in "field studies".
      METHODS: The method is based on commercially-available kits, and involves in loco
      treatment. Whole blood is labeled with monoclonal antibodies, and fixed samples
      immediately after collection. After the treatment, the samples are ready for flow
      cytometric analysis, which may be performed after a two-day period from sample
      collection. RESULTS AND CONCLUSION: The method described is adequate for
      immunotoxicity testing in field studies because it prolongs the maximum latency
      time from collection and cytofluorimetric analysis up to 48 hours. A second
      interesting characteristic of the method is the possibility of using whole blood,
      without any need of either complex manipulations or particular equipment.

PMID- 12197272
TI  - [Immunologic effects of exposure to low levels of inorganic mercury].
AB  - OBJECTIVE: The immune system is a target for the toxic effects of inorganic
      mercury, both in humans and animals. In humans it has been observed that
      occupational and environmental exposure to inorganic mercury may cause both
      clinical (autoimmunity, hypersensitivity) and subclinical effects (cellular and
      humoral immunologic variable modifications). To obtain a better definition of
      these effects with respect to the exposure levels, a multicentre study was
      performed on 117 workers exposed to very low doses of inorganic mercury and 172
      subjects from the general population of the same geographical area with
      environmental exposure to mercury from dental amalgams and dietary fish intake.
      RESULTS: The white blood cell count was included in the normality range for all
      subjects and there was no difference between exposed and non exposed subjects.
      The immunologic variables studied showed an increase of the CD4+ and CD8+ number
      in exposed workers compared to non-exposed subjects, with a statistically
      significance only for CD4+, while no difference was observed regarding CD4+,
      CD8+, NK+ percentage and CD4+/CD8+ ratio. A significative decrease of serum IL-8
      and an inverse correlation between serum levels of this cytokine and HgU were
      observed in exposed workers compared to non exposed subjects. No association
      between immunologic variables and both dental amalgams and dietary fish intake
      was found in subjects not occupationally exposed to inorganic mercury.
      DISCUSSION: The decrease in IL-8 serum levels observed in exposed workers might
      suggest an immunosuppressive effect of occupational exposure to very low doses of
      inorganic mercury. This result suggests the need to revise of current HgU BEI
      after further definition of its prognostic significance.

PMID- 12197274
TI  - [Evaluation of the neurotoxic and nephrotoxic effects following long-term
      exposure to metallic mercury in employed at a chlorine/sodium-hydroxide plant].
AB  - OBJECTIVES: Within the frame work of a wide multicentre study, a sub-study was
      developed in order to explore the occurrence of early effects on the central
      nervous system, on the kidney and on the neuro-immune system in the workers of a
      chloro-alkali production plant exposed to metallic mercury at airborne
      concentration levels lower than 0.025 mg/m3 (TLV-TWA). They were compared to a
      control population of employees of the same huge petrochemical plant with
      different job that did not implicate exposure to mercury vapors. Specifically,
      the study aimed at revealing the occurrence of early effects on the central
      nervous system related with mercury exposure, as can be assessed through
      neurophysiological and neurobehavioral tests. METHODS: The excretion of urinary
      mercury was measured by atomic absorption spectrometry. The study of renal
      function was assessed by measurement of the urinary excretion of some high and
      low molecular weight protein markers (albumin, beta 2-microglobulin, retinol
      binding protein, fibronectin, specific proximal tubule brush border antigens, N
      acetyl-beta-D-glucosaminidase). The neurobehavioral status of the study subjects
      was assessed by means of several test parameters (Simple Reaction Time, Color
      Word Vigilance Test, Symbol Digit, Finger Tapping, Mood Scale of Kjellberg and
      Iwanowski, Subjective symptoms questionnaire (QSS), Luria Nebraska Motor Scale,
      Branches Alternate Movement Task and Tremometry). RESULTS: The values of urinary
      excretion averaged 12 +/- 8 micrograms Hg/g of creatinine for the exposed workers
      group (n = 38), while for the reference group (n = 34 cases) urinary excretion
      was statistically lower, averaging 4 +/- 6 micrograms Hg/g of creatinine. Neither
      the parameters selected for the assessment of renal functions, nor those chosen
      to probe the neurobehavioral status of the probands revealed statistically
      reliable differences between the group of exposed workers (length of exposure:
      range 1-34 years) and the control group. Nevertheless, some minor but still
      statistically reliable correlations were found between some neurobehavioral
      parameters and some demographic variables describing the whole group of tested
      workers, but not to the level of occupational exposure to mercury. CONCLUSIONS:
      The results of the study confirm the lack of toxic effects of clinical importance
      on the central nervous system and on the kidney for values of mercury urinary
      excretion lower than the suggested index of biological exposure (IBE) of 35
      micrograms Hg/gram of creatinine.

PMID- 12197275
TI  - [Use of regression analysis in the study of the association between different
      mercury exposure routes and some functional variables].
AB  - AIMS: The "Mercury Multicentric Project" data-set was analysed with the aim to
      identify a group of biological variables associated with different types of Hg
      exposure (occupational exposure, fish dietary intake, exposure due to amalgam
      restorations). The distribution of socio-demographic, biological and surrogate
      outcome variables was rather different among the collaborating Units. METHODS:
      Mixed linear models (MLM) were used to overcome the problems related to the
      heterogeneity of variances among Units. MLM are a generalization of the standard
      linear models, the generalization being that the data are permitted to exhibit
      correlation and non constant variability. MLM therefore provide with the
      flexibility of modelling not only the means of the dependent variable, but also
      their variances and co-variances as well. This allows to represent the total
      variability of the dependent variable as a sum of two components: the first
      attributable to the Units and the other one to the random error. RESULTS AND
      CONCLUSIONS: A set of biological variables significantly associated with at least
      one of the Hg exposure variables or with the HgU/creatinine ratio (as surrogate
      variable for Hg exposure) was identified by means of MLM. This set includes beta
      2-MG, sIL8, CD4+, sPRL, FT dominant, BAMT, and some variables related to
      neurological behaviour. An extension of this analysis will be performed with a
      structural equations approach in order to study the dose-response relationships
      among the various variables according to a hierarchical path defined on
      biological basis. One of the possible simplified general models including all the
      selected variables is described.

PMID- 12197276
TI  - Synthesis of the results of studies performed on subjects exposed to low doses of
      mercury.

PMID- 12197278
TI  - [In vitro study of transcutaneous inorganic mercury absorption from solid soil].
AB  - OBJECTIVES: Skin is such an important route of absorption of mercury compounds
      that the ACGIH has assigned them a skin notation. Soil has been recognised as a
      potential source of exposure to chemical contaminants. It therefore seems
      advisable to establish maximum daily exposure levels for mercury in soil. In the
      past, areas adjacent to certain industries and smelters were heavily contaminated
      by mercury. For example, on Monte Amiata in Tuscany, which was an important
      mercury mining and production centre in the past, several areas have been
      polluted. To understand the dermal uptake of chemicals bound to soil and dust,
      information on the pure substance is helpful but does not seem sufficient. Other
      factors must be accounted for, that can easily be reproduced and controlled in in
      vitro experiments. METHODS: Using an in vitro diffusion cell system and human
      skin, we studied percutaneous penetration of mercury chloride (HgCl2) at
      different concentrations, with particular emphasis on skin absorption from soil.
      The test apparatus consisted of a flow-through diffusion cell system. Dermotomed
      human cadaver skin was used as the membrane, while the receiving liquid was a
      saline solution with 6% PEG-20 oleyl-ether and gentamycin sulphate. Mercury
      chloride was applied at two different concentrations using a buffered solution
      and soil as vehicles. RESULTS AND CONCLUSIONS: Increments of percentage of
      absorption at the different hours were found to be significantly lower in the
      cells where the higher concentration of mercury chloride was applied. In the
      receiving fluid of cells where soil was used as vehicle, the concentration of
      mercury was always below the detection limit. Skin contamination with soil
      containing inorganic mercury does not seem to be a dermal risk.

PMID- 12197277
TI  - [In vitro study of the nephrotoxic mechanism of mercuric chloride].
AB  - OBJECTIVES: Mercury (Hg), one of the most diffused and hazardous organ-specific
      environmental contaminants, exists in a wide variety of physical and chemical
      states, each of which with unique characteristics of target organ specificity.
      Exposure to Hg vapour and to organic mercurials specifically affects the CNS,
      while the kidney is the target organ for inorganic Hg compounds. Despite the
      increasing number of studies, the molecular bases of the nephrotoxic potential of
      Hg has not, up to now, been clarified, even if there is evidence suggesting that
      the ability of the metal to interact with proteins (thiol groups) or to generate
      oxygen radicals may play a major role. Within this context, the aim of the
      present study was to investigate, in vitro, the mechanism(s) of the early
      nephrotoxic potential of mercury chloride (HgCl2), one of the most diffused and
      biologically active mercury (Hg2+) compounds. For this purpose, two kidney
      derived in vitro systems (the MDCK and the LLC-PK1 cell lines) were tested for
      their sensitivity to the salt, and MDCK was chosen as the most suitable in vitro
      model for our study. As possible biological markers of the organ-specific
      toxicity of the metal we analysed: i) critical biochemical parameters related to
      oxidative stress conditions (effect of Hg2+ on the anti-oxidant status of the
      cell), and ii) gap-junctional function (GJIC). METHODS: Classical toxicity tests
      (MTT and NR) were used for assessing the sensitivity (IC50) of LLP-CK1 and MDCK
      cell lines to the mercuric salt. Complete solubilisation of the salt in the
      culture media was verified by inductively coupled plasma mass spectrometry (ICP
      MS). The influence of the metal on cell growth rate and viability were evaluated
      by conventional proliferation assays. For the following mechanistic studies,
      cells were exposed for different time periods (4 to 72 hours) to non-cytotoxic
      (0.1-50 microM) HgCl2 concentrations. The biochemical analysis of the pro-oxidant
      properties of the mercuric compound was performed by the measurement of anti
      oxidant cellular defences against H2O2 [catalase (Cat), glutathione peroxidase
      (Gpx), and total glutathione (GSH)]. The influence of the metal on the GJIC
      capacity of MDCK cells was assessed by the "microinjection/dye-coupling" assay.
      RESULTS: Among the two kidney-derived in vitro systems, MDCK cell line was the
      most specifically sensitive to the toxic effect of HgCl2: it was, consequently,
      chosen as a "tubular cell model" for the following experimental steps. Tested for
      various time periods at increasing concentrations, the HgCl2 effect on MDCK cell
      proliferation and viability was found to be time- and dose-related. For
      concentrations < or = 50 microM, HgCl2 inhibits MDCK cell growth rate, being this
      effect significant (> 50% in respect to untreated controls) from the 24th from
      the beginning of the treatment, while, for concentrations > 50 microM, the metal
      causes cell death. Concerning the influence of HgCl2 on MDCK anti-oxidant
      defences, the most interesting results were obtained by analysing the influence
      of the mercury salt on the GSH cell content and Gpx activity. Both were, in fact,
      significantly affected by the presence of the mercury ion. HgCl2 also induced a
      rapid, dose- and time-related inhibitory effect on the GJIC capacity of the
      cells. CONCLUSIONS: Even if further investigations are needed to better clarify
      the possible causal relationship between our findings, they indicate that: a)
      MDCK cells represent a suitable in vitro model for the study of Hg
      nephrotoxicity; b) GJIC function is, among those considered in our study, one of
      the most sensitive biological endpoints for investigating the mechanism(s) of
      Hg2+ specific toxicity.

PMID- 12197281
TI  - [Surgical management of trauma: from the "golden hour" to the "Golden Day"].
AB  - The treatment of the "trauma" has individualized objective therapeutic to reach
      in the first phase of clinical management defined by Mattox in the concept of the
      Golden Hour, that consist to transport the patient to the fittest hospital and to
      recognize and to treat the priorities "ABCDE", identifies in ATLS Guideline. The
      evolution of the organization for the treatment of the trauma has developed the
      concept of Trauma System to whose apex there are of the structures devoted define
      Trauma Center, with specificity of structures and functions, personal devoted
      fully grown with a specific run. In the Trauma Center is possible to get a
      therapeutic planning according to the priorities of the case in few times so that
      to not only achieve the objective to treat in emergency the vital lesions, but to
      do the necessary treatments precociously to prevent the compliances of the
      patient, that is checked in environment then multidisciplinary intensive care.
      This systematic treatment by objective it allows to identify some Guideline of
      surgical treatment for priority in once defined Golden Day.

PMID- 12197279
TI  - [In vitro study of amalgam corrosion].
AB  - AIMS: In the dental field, the aim of the research was to evaluate, through a
      standardized system, the factors influencing the corrosion of dental alloys in
      different clinical conditions with various types of amalgams and/or solution
      parameters. METHODS: A 6-hole corrosion cell was used according to ASTM G5-95
      protocol. RESULTS AND CONCLUSIONS: It is well known that free surface corrosion
      is uncommon in the oral cavity in the case of most dental alloys. But localized
      corrosion, either as pitting or as crevice corrosion, might occur. The clinical
      conditions affecting amalgam corrosion may be detectable in localized corrosion,
      in particular because of cathodic/anodic surface behaviour coupling.

PMID- 12197280
TI  - [Evaluation of the effects following low doses of inorganic mercury from
      environmental and occupational exposures].
AB  - AIMS: This paper reviews the studies, both in vivo and in vitro, carried out for
      the project on low-dose effects of inorganic mercury, financed by the Italian
      Ministry of Universities and Scientific and Technological Research. RESULTS,
      COMMENTS AND PROPOSAL: The results offer both innovative aspects and potential
      practical applications. Particular attention is drawn to the reliability of
      biomarkers of exposure [mercury in urine (HgU) and blood (HgB), possibility of
      speciation] as well as to the availability of guidance values for risk assessment
      (reference value, action level, biological threshold value). In the general
      population, HgU and HgB levels are significantly related to the presence of
      dental amalgams and to fish consumption; nevertheless, such exposure levels do
      not elicit adverse health effects on renal, immune and nervous functions,
      according to the markers evaluated in the studies. The present biological
      threshold values for occupational exposure appear adequate to prevent health
      effects, considering the immune system, kidney and central nervous system as the
      target organs. However, possible effects of low doses of mercury on immune and
      neuroendocrine functions should be further examined; moreover, consideration
      should be given to the risk of consuming fish species with high Hg content,
      particularly concerning the renal and central nervous system effects. Finally,
      further studies should be planned on other potentially important effects, that
      could not be considered in this study, such as those on prenatal development, the
      cardiovascular system and the thyroid gland.

PMID- 12197282
TI  - [Reoperations in lung surgery].
AB  - A second thoracotomy in patients who have undergone previous chest surgery can be
      performed soon or immediately after the first operation and is usually aimed at
      resolving severe or even life-threatening postoperative complications. Late
      reoperations, on the other hand, are either performed to resolve complications of
      previous surgery or to remove second primary lung tumors (SPLCs) or metastases.
      The most exacting reoperation in this context is completion pneumonectomy, which
      is particularly indicated in the case of failure of the residual lobe to re
      expand after primary surgery; it is also used for--rarely occurring--fistulas of
      the lobar bronchi and for new ipsilateral primary lung tumors. This type of
      surgery is technically complicated and has been associated, in our experience and
      that of others, with a certain mortality. Technically less difficult is a second
      ipsilateral thoracotomy for exploratory purposes or minor parenchymal resection,
      and the same is true of contralateral lobar or sublobar resections. Lastly,
      Abruzzini's operation, for fistulas of the primary bronchus, is relatively
      complicated but often leads to good results; we have performed 15 such operations
      with only one death occurring due to acute myocardial infarction.

PMID- 12197283
TI  - Malignant thymoma invading pulmonary artery. Changing treatment options.
AB  - BACKGROUND: Curative treatment of malignant thymoma is resection; however, this
      may be precluded by invasion of vital organs. PATIENTS AND METHODS: Two patients
      with extensive intrathoracic spread of thymoma (Stages III and IV A) are
      presented. Treatment involved a combination of resection, radiotherapy and
      chemotherapy. RESULTS: One patient survived 9 years, 4 months, but eventually
      died of metastatic spread; the other one is well and without evidence of disease
      30 months after treatment. CONCLUSIONS: Thymoma is a slow-growing tumor.
      Successful surgical treatment in advanced cases is possible, if aided by
      radiotherapy and chemotherapy. The adjuvant therapy converts a non-resectable
      tumor to a resectable one.

PMID- 12197284
TI  - [Neurogenic tumors of the mediastinum].
AB  - Neurogenic neoplasms represent approximately 20% of the space-occupying lesions
      in the mediastinum. They are primary tumors originating from structures belonging
      to the peripheral or sympathetic nervous system, they are most commonly diagnosed
      in subjects in the age range between 10 and 30 years. Benign forms are
      significantly more frequent than malignant forms, an observation that was
      confirmed by our own experience; whether these tumors have a predilection for the
      male or female sex cannot be concluded from the various case series studied to
      date. Surgical resection can be considered the treatment of choice on the basis
      of the long-term results, which are greatly satisfactory in benign tumors and
      encouraging in the malignant variants.

PMID- 12197285
TI  - [Aneurysms of the superior mesenteric artery].
AB  - Splanchnic arteries aneurysmatic pathology is rare, even if, in the last decades
      it has been noticed an increase of its incidence, owing to the worldwide use of
      the recent diagnostic tools as echography, TC, MR and angiography. Among visceral
      aneurysms those of the superior mesenteric artery (SMA) range the 5.5-8%. In the
      majority of cases SMA aneurysms are of mycotic etiology (60%), of atherosclerotic
      ones are less frequent, even if their incidence has increased in the last
      decades. Other causes are exceptional. Dimensions are generally moderate (1-3
      cm.), yet aneurysms of a significant diameter, ranging from 4 to 8 cm., are
      reported in the most recent literature. Aneurysms can be symptomatic with
      abdominal upper quadrants pain, due to the compressive mass effect on the
      contiguous structures. In some cases typical signs of claudication abdominis are
      present. A pulsating epi-mesogastric abdominal mass is present in the 50% of
      subjects. In the 20% of the cases the patients come to medical attention
      presenting a situation of hemorrhagic shock for aneurysmatic rupture in the
      peritoneal cavity, or in the digestive tract, considering also the possibility of
      a thrombosis with consequent acute bowel ischemia. Urgent surgical operations,
      when possible, imply an high mortality rate. For these reasons, there is
      indication of elective surgery for all SMA aneurysms, both symptomatic and of
      occasional finding. The performable surgical techniques are: proximal and distal
      ligation, with or without aneurysmectomy, that is the most utilized because
      commonly performed during emergency operations. This technique requires the
      presence of a sufficient collateral vascular supply. Endoaneurysmorraphy can be
      performed only in the case of mild-dimension saccular aneurysms.
      Revascularization techniques through substitution or by-pass are mandatory in
      managing voluminous mass aneurysms. It is reported a case of SMA aneurysm of
      exceptional dimensions (diameter approximatively 10 cm.) that for its enormous
      volume substituted completely the mesenteric axis, involving the origin of the
      jejuno-ileal and ileo-colic branches. In this case it has been mandatory the
      performing of the aorto-mesenteric by-pass technique, distally patch modelled and
      sutured to the residual posterior SMA wall, on the purpose to allow the
      revascularization of the emerging jejunal arteries and adapted to the residual
      distal stump to irrorate ileo-colic branches.

PMID- 12197286
TI  - [Billiopancreatic diversion with preservation of the duodenal bulb and transitory
      gastroplasty in the treatment of morbid obesity. Our experience].
AB  - We present our experience in malabsorbitive procedure in bariatric surgery based
      on Biliopancreatic Diversion (BPD) with transitory gastroplasty. Since 1995 we
      operated on 74 patients with BPD coupled with gastroplasty which is transitory
      due to the presence of a band in polidioxanone (PDS). The technique, proposed by
      Vassallo et al. in 1992, involve the respect of the duodenal bulb (5 centimeter
      from the pylorous) making an end-to-side duodeno-ileal isoperistaltic
      anastomosis. The initial excess weight loss was satisfactory (69.8% +/- 11.4%
      after 1 year) and it kept being stable during all the follow-up (75.2% +/- 6.4%
      after 5 years). The mortality was absence. We didn't observe ipoalbuminemia,
      diarrhea or halitosis in any patients. Only 1 patient (1.3%) developed an
      anastomotic ulcer. After 5 years follow-up we observed 2 cases (12.5%) of chronic
      hypochromic anemia and 1 case (6.2%) of hypocalcemia. We didn't perform any
      restorative operation. We consider this technique a good malabsortive procedure
      able to obtain a satisfactory and stable weight loss, with a low incidence of
      complications. Moreover it could be applied in patients previously treated by an
      ineffective gastroplasty.

PMID- 12197287
TI  - [Use of abdominal wall retractor Laparo Tenser in gasless laparoscopic
      cholecystectomy].
AB  - High pressure CO2-peritoneum for laparoscopic surgery is not indicated in
      patients with impairment of cardiorespiratory and renal function and in high risk
      patients and in obesity. On the other site the uncontrolled abdominal
      insufflation and the blind insertion of the first trocar in patients with
      extended intraperitoneal adhesions, often cause bleeding and the intestinal loops
      dislocation, and can determine visceral lesions. In these patients gasless
      technique with an abdominal laparolifter can be employed. We report an experience
      of 36 patients undergoing laparoscopic cholecystectomy by a subcutaneous planar
      retractor. It was observed a good operative exposure in 83.3%; the surgery was
      safely performed in 88.8%. Two suprafascial hematoma related to the insertion of
      the needles of the Laparo Tenser occurred. A regular post-operative discharge was
      observed in 84.4%. These good results supports the extension of the laparoscopic
      approach for the cholecystectomy to complicated or to high risk patients.

PMID- 12197288
TI  - Efficacy and safety of elective laparoscopic cholecystectomy in elderly: a case
      controlled comparison with the open approach.
AB  - BACKGROUND: Minimally invasive laparoscopic surgery is the method of choice for
      the surgical treatment of gallbladder disease. However, surgery of the biliary
      tract in the elderly is often associated with high morbidity and mortality.
      PATIENTS AND METHOD: To evaluate the efficacy and safety of the laparoscopic
      cholecystectomy in the elderly with symptomatic, uncomplicated gallbladder
      disease, we retrospectively compared the records of 24 consecutive patients over
      70 years of age with symptomatic uncomplicated gallbladder disease, who underwent
      elective laparoscopic cholecystectomy, with a similar cohort of patients who
      underwent elective open cholecystectomy for the same indications. RESULTS: In the
      laparoscopic group we found a significantly low incidence of postoperative
      complications, low analgesics and antibiotics administration, rapid recovery,
      short length of stay and considerable cost savings. CONCLUSION: We conclude that
      elective laparoscopic cholecystectomy in elderly with uncomplicated gallbladder
      disease is safe and effective and we suggest that it may become the surgical
      procedure of choice.

PMID- 12197289
TI  - [Course and natural history of idiopathic ulcerative proctitis in adults].
AB  - BACKGROUND AND AIMS: Epidemiological studies have shown that ulcerative proctitis
      represents 25-55% of ulcerative colitis. In western countries, the incidence of
      ulcerative proctitis has been increased, while the incidence of more extensive
      colitis remained unchanged. Compared with extensive ulcerative colitis, the
      idiopathic proctitis seems to be a benign disease, with an extension to proximal
      segments in less than 30% of cases, low surgical and cancer risk. On the basis of
      epidemiological studies, not confirmed by endoscopic and histological features,
      it has been hypothesized that ulcerative colitis and proctitis could represent
      two different clinical entities. The aim of the study was to evaluate some
      clinical and demographic features related to the two different localizations,
      colitis and proctitis, in the attempt to clarify the above mentioned issues.
      METHODS: Demographic data of 156 patients observed in our institution from 1982
      to 1999, were retrospectively analysed. Diagnosis, extension and severity of
      ulcerative procto-colitis were based on endoscopic and histological criteria.
      Local and systemic symptoms, extraintestinal manifestations, surgical and cancer
      risk, were also recorded. RESULTS AND CONCLUSIONS: Ulcerative proctitis has shown
      to be a benign disease, with a prevalence of local symptoms, less systemic and
      extraintestinal manifestations, and low endoscopic grades of activity.
      Furthermore no surgical intervention and cancer development were recorded.
      Extension to proximal segments was observed in 10.25% of cases. Young age of
      onset of symptoms,-smoking and appendectomy were associated to an higher risk of
      extension of the disease.

PMID- 12197291
TI  - [Emergency surgery of colorectal cancer in patients older than 80 years of age].
AB  - AIM: In elderly people colorectal cancer has an high incidence of emergency
      presentation. In this article we report our experience on colorectal emergency
      surgery for cancers in patients older than 80 yrs. METHODS: From October 1995 to
      December 2000 323 patients were submitted to emergency surgical procedure for
      colorectal cancer at the Dpt of Emergency Surgery of University of Bologna. 37
      (11%) subjects were over 80 years of age. A retrospective analysis was performed:
      the data collected included the mode of presentation of the patients, the
      location and Dukes' classification of the tumors, the incidence of radical and
      palliative operations, the causes of death and 30-day mortality. RESULTS: The
      most common emergency presentation was an intestinal occlusion (21 cases); the
      other different presentations were peritonitis (7 cases) and hemorrhage (9
      cases). 22 patients underwent resection of the primary growth and anastomosis and
      11 subjects had palliative intervention by creating a stoma only or bypass
      anastomosis without resection, 2 patients had an explorative laparotomy and 2
      were inoperable. Our overall postoperative mortality was 14.2% and we registered
      1 anastomotic leakage. DISCUSSION AND CONCLUSIONS: Emergency surgery for
      colorectal cancer in patients over 80 years of age can be performed safely
      without restrictions related to the age.

PMID- 12197290
TI  - [Aspects of the complications after restorative proctocolectomy in the treatment
      of ulcerative colitis. Review of the literature and personal experience].
AB  - PURPOSE: Analysis of complications and causes of failure after stapled
      restorative proctocolectomy with ileal J pouchanal anastomosis in patients with
      ulcerative colitis is presented. PATIENTS AND METHODS: The procedure was
      performed in 28 patients, 19 males (68%) and 9 females (32%); diverting ileostomy
      was always performed. RESULTS: There was no perioperative mortality. The overall
      morbidity rate was 31%. Six patients (21%) had pelvic abscess, 2 (7%) pelvic
      hematoma, 4 patients (14%) presented ileo-anal anastomotic stricture, 1 patient
      (3.6%) had pouch-vaginal fistula, three patients (11%) presented intestinal
      obstruction and 7 (25%) pouchitis. Reoperation was necessary in patients with
      small bowel obstruction and with pouch-vaginal fistula. Septic complications and
      pouchitis were resolved with medical treatment. Stenosis of the anastomosis
      required anal dilation. No patient underwent pouch excision for pouch failure.
      CONCLUSION: The main significant complications of ileal pouch-anal anastomosis
      for ulcerative colitis were pelvic sepsis, intestinal obstruction and pouchitis.
      Our results suggest that the use of stapling technique is safer and has fewer
      early septic complications and sepsis-related pouch removals. Success in ileo
      anal construction increases with experience. The selection of patients with
      exclusion of Crohn disease, a correct surgical timing, a carefully technique, a
      delayed ileostomy closure and a low pre and postoperative regimen of steroids are
      important factors of success.

PMID- 12197292
TI  - [Hemorrhoidectomy with stapler vs. traditional hemorrhoidectomy: comparative
      outcome of 2 groups of patients].
AB  - Authors compare the results of two groups of patients, with III and IV degree
      haemorrhoids. The first group (48 patients) were treated with traditional
      surgery, open or closed. The second group (42 patients) treated with stapling
      haemorrhoidectomy. The groups were compared in order to determine if a true
      advantage exists regarding post-operative pain and functional recovery. Authors
      conclude that stapler haemorrhoidectomy, is somehow better in reducing the pain
      and offers a quick functional recovery. But the technique must be adopted in
      selected patients with mucosal prolapse, when the haemorrhoidal plexus is below
      the dentate line. In those cases, with inveterate mucosal prolapse, and thickened
      external fibrous tissue, or an irreducible prolapse of the external haemorrhoidal
      plexus, the choice must be carefully evaluated.

PMID- 12197293
TI  - Surgical conservative treatment for Bauhin's syndrome.
AB  - BACKGROUND AND STUDY AIMS: Hypertrophy of ileocaecal sphincter seems to be the
      basic etiological factor of Bauhin's valve syndrome (BVS). In the rare literature
      all cases are treated by means of an hemicolectomy. A patient with Bauhin's valve
      syndrome is described, whose pathologic characteristics were hypertrophy of
      ileocaecal sphincter and a circular submucosal lipoma on the caecal side of the
      valve. Lipomata, although uncommon, may arise throughout the whole
      gastrointestinal tract, mostly asymptomatic, and submucosal layer is most
      frequently involved than subserosal one. More than two-thirds of gut lipoma are
      found in the large bowel, where they represent the most common benign lesion
      after adenoma. PATIENTS AND METHODS: A 36 year old woman suffering from periodic
      upper abdominal pain, nausea and diarrhea, was submitted to an explorative
      surgical procedure, after imaging study of the bowel showed only an indistict
      mass in the caecum. Though a caecotomy a dissection of an hypertrophic and
      swollen portion of the ileocaecal valve was performed, saving the ileo-caecal
      sphincter. The residual mucosal margins were sutured, the last tract of the ileum
      was fixed to the caecum, completing with a caecorrhaphy and appendectomy.
      RESULTS: Normal post-operative period, discharging the patient after few days.
      Since the operation all symptoms disappeared, and after four years there is a
      total well-being of the patient with complete disappearance of the former
      symptoms. CONCLUSIONS: If the BVS is only due to a lipomatous hypertrophy of the
      mucosa and submucosa of ileo-caecal valve, hemicholectomy seems to be not
      justified: it is an exceedingly invasive procedure for a non-malignant disease.
      It is important a throughout radiological diagnosis and a caecotomy direct
      control during an operative exploration for a correct surgical choice.

PMID- 12197294
TI  - [Objectives of a bloodless surgery program. A comparative study (major surgery
      vs. minor-medium surgery) in 51 Jehova's Witnesses patients].
AB  - AIM: The purpose of this retrospective review of the charts of 51 Jehovah's
      Witness patients, who underwent surgery without blood transfusions, was to
      compare two study groups (major surgery vs minor-medium surgery). METHODS: We
      compared the following variables: age, sex, length of stay, type of surgical
      operation, use of intraoperative red cell salvaging devices, hemodilution, number
      of drainages and their stay, postoperative blood loss, complications, need of
      reoperation and mortality rate. Between medical variables we focused on blood
      production therapy and nutritional support (administration of iron, folate,
      erythropoietin and albumin) and blood tests (at the first day of admission;
      intraoperative; at the first postoperative day; at the discharge). RESULTS: In
      the two study groups, we detected statistically significant differences in the
      following variables: total of postoperative blood loss (p < 0.00001),
      complications rate (p = 0.0122) and in Hgb values (intraoperative: p = 0.0197; at
      the first postoperative day: p = 0.0028; at the discharge: p = 0.0100).
      DISCUSSION: The aims of a bloodless surgery program are: 1) minimize blood loss,
      reducing iatrogenic anemia and intraoperative hemorrhage loss; 2) maximize blood
      production by administration of erythropoietin, iron and folate; 3) maximize
      cardiac output by alternatives to blood transfusions, as crystalloids, colloids
      and blood substitutes; 4) increase oxygen content; 5) decrease metabolic rate. We
      focused on advantages and disadvantages of the suggested procedures. Most
      interesting techniques are the normovolemic hemodilution and the intraoperative
      red cell salvaging devices, indispensable in emergency. CONCLUSIONS: A close team
      work between surgeons, anesthesiologists and hematologists is determinant in a
      reference center that guarantees experience, organization, professionality,
      respect for the patients' will and, above all, low morbidity and mortality rates,
      as those reported by our series.

PMID- 12197295
TI  - [Use of the Dynamic Stent in the palliation of carinal and distal tracheal
      stenosis].
AB  - Satisfactory palliation of the lesions involving the carinal region is difficult
      to achieve because the stenting is conducted in an unsuitable anatomy, in highly
      symptomatic patients. During the period 1987-2000 we performed 785 operative
      rigid bronchoscopies in 524 patients, 184 of whom received a respiratory stent.
      The stenting of the carinal region was carried out in 27 patients with the use of
      the Frietag Dynamic stent. In this group of patients indication for stenting was
      as follows:--advanced lung cancer (22);--esophageal cancer invading the lower
      trachea (1);--severe tracheobronchomalacia (2);--postintubation stenosis of the
      lower trachea (2). No perioperative mortality was observed. All patients
      experienced symptomatic improvement. Follow-up ranged from 1 to 60 months: all
      neoplastic patients died for advanced disease without significant respiratory
      problems with a median survival of 5.6 months; three patients treated for benign
      diseases are still alive at 2, 31 and 65 months from stent deployment. No major
      complications were observed: in two patients the stent was removed after few days
      due to mucous retention; furthermore we observed symptomatic respiratory
      infections caused by a residual space between the tracheal wall and the
      prosthesis in other two patients with severe COPD. Dynamic stent is to be
      considered the stent of choice for palliation of the carinal region because it is
      effective and well tolerated with a low complications rate. The main limitations
      of such prosthesis are the shortness of the right bronchial branch and the size,
      sometimes inadequate.

PMID- 12197296
TI  - [Aneurysms of the visceral arteries: report of 5 cases].
AB  - Visceral artery aneurysms are uncommon and usually result from atherosclerosis,
      periarteritis nodosa and fibromuscular dysplasia. Hepatic artery aneurysms were
      detected in two patient, splenic artery aneurysms in three. In four patients
      rupture occurred. In the two patients with hepatic artery aneurysm hemobilia from
      arterial rupture into the common bile duct and intraperitoneal bleeding in lesser
      sac was assessed. Ruptured aneurysms of the splenic artery with free
      intraperitoneal bleeding occurred in two patients, one patient had an
      asymptomatic splenic artery aneurysm. In four patients the diagnosis was made by
      contrast-TC and/or celiac and mesenteric angiography. In four patients excision
      of the aneurysm was successfully performed. One patient with ruptured hepatic
      artery aneurysm and in which resection and revascularization was made died.

PMID- 12197297
TI  - Analysis of data with excess zeros.
AB  - This paper is an introduction to a set of papers on two-part models that were
      presented at the 2000 Joint Statistical Meetings of American Statistical
      Association, International Biometric Society (ENAR), International Biometric
      Society (WNAR), Institute of Mathematical Statistics, and Statistical Society of
      Canada. The second part of the paper summarizes results of a study of the size
      and power of two-part models. It proposes that two-part models are a useful
      alternative to the t-test and the Wilcoxon test.

PMID- 12197298
TI  - Repeated measures with zeros.
AB  - Consider repeated measures data with many zeros. For the case with one grouping
      factor and one repeated measure, we examine several models, assuming that the
      nonzero data are roughly lognormal. One of the simplest approaches is to model
      the zeros as left-censored observations from the lognormal distribution. A random
      effect is assumed for subjects. The censored model makes a strong assumption
      about the relationship between the zeros and the nonzero values. To check on
      this, you can instead assume that some of the zeros are 'true' zeros and model
      them as Bernoulli. Then the other values are modeled with a censored lognormal. A
      logistic model is used for the Bernoulli p, the probability of a true nonzero.
      The fit of the pure left-censored lognormal can be assessed by testing the
      hypothesis that p is 1, as described by Moulton and Halsey. The model can also be
      simplified by omitting the censoring, leaving a logistic model for the zeros and
      a lognormal model for the nonzero values. This is approximately equivalent to
      modeling the zero and nonzero values separately, a two-part model. In contrast to
      the censored model, this model assumes only a slight relationship (a covariance
      component) between the occurrence of zeros and the size of the nonzero values.
      The models are compared in terms of an example with data from children's private
      speech.

PMID- 12197299
TI  - Mixture models for quantitative HIV RNA data.
AB  - Clinical investigators are increasing their use of quantitative determinations of
      HIV viral load in their study populations. The distributions of these measures
      may be highly skewed, left-censored, and with an extra spike below the detection
      limit of the assay. We recommended use of a mixture model in this situation, with
      two sets of explanatory covariates. We extend this model to incorporate multiple
      measures across time, and to employ shared parameters as a way of increasing
      model efficiency and parsimony. Data from a cohort of HIV-infected men are used
      to illustrate these features, and simulations are performed to assess the utility
      of shared parameters.

PMID- 12197300
TI  - Inferences about population means of health care costs.
AB  - The analysis of health care costs is complicated by the skewed and
      heteroscedastic nature of their distribution with possibly additional zero
      values. Statistical methods that do not adjust for these features can lead to
      incorrect conclusions. This paper reviews recent developments in statistical
      methods for the analysis of health care costs; our focus is on population means.

PMID- 12197301
TI  - Analysis of repeated measures data with clumping at zero.
AB  - Longitudinal or repeated measures data with clumping at zero occur in many
      applications in biometrics, including health policy research, epidemiology,
      nutrition, and meteorology. These data exhibit correlation because they are
      measured on the same subject over time or because subjects may be considered
      repeated measures within a larger unit such as a family. They present special
      challenges because of the extreme non-normality of the distributions involved. A
      model for repeated measures data with clumping at zero, using a mixed-effects
      mixed-distribution model with correlated random effects, is presented. The model
      contains components to model the probability of a nonzero value and the mean of
      nonzero values, allowing for repeated measurements using random effects and
      allowing for correlation between the two components. Methods for describing the
      effect of predictor variables on the probability of nonzero values, on the mean
      of nonzero values, and on the overall mean amount are given. This interpretation
      also applies to the mixed-distribution model for cross-sectional data. The
      proposed methods are illustrated with analyses of effects of several covariates
      on medical expenditures in 1996 for subjects clustered within households using
      data from the Medical Expenditure Panel Survey.

PMID- 12197302
TI  - Understanding protein folding with energy landscape theory. Part I: Basic
      concepts.

PMID- 12197303
TI  - A review of DNA sequencing techniques.
AB  - The four best known DNA sequencing techniques are reviewed. Important practical
      issues covered are read-length, speed, accuracy, throughput, cost, as well as the
      automation of sample handling and preparation. The methods reviewed are: (i) the
      Sanger method and its most important variants (enzymic methods); (ii) the Maxam &
      Gilbert method and other chemical methods; (iii) the Pyrosequencing method--DNA
      sequencing in real time by the detection of released pyrophosphate (PPi); and
      (iv) single molecule sequencing with exonuclease (exonuclease digestion of a
      single molecule composed of a single strand of fluorescently labelled
      deoxynucleotides). Each method is briefly described, the current literature is
      covered, advantages, disadvantages, and the most suitable applications of each
      method are discussed.

PMID- 12197304
TI  - Max Perutz (1914-2002).

PMID- 12197305
TI  - Web alert. The chemistry of drug design and lead optimization.

PMID- 12197306
TI  - Osteoporosis: challenges and new opportunities for therapy.
AB  - Osteoporosis is a chronic disease that affects a large number of both men and
      women and is characterized by a decrease in bone mass, as well as weakened bones.
      It causes a significant amount of morbidity and mortality in patients and is
      often only diagnosed after a fracture occurs. This review will highlight recent
      advances in the development of novel anabolic approaches for treatment of
      osteoporosis, such as parathyroid hormone (PTH), calcium sensing receptor
      modulators, statins and prostanoid receptor agonists. Selected antiresorptive
      targets (cathepsin K inhibitors and vitronectin receptor antagonists) will also
      be surveyed.

PMID- 12197307
TI  - Recent advances in the discovery of small molecule histone deacetylase
      inhibitors.
AB  - The reversible acetylation of lysine amino groups in nuclear histones is an
      important mechanism by which gene expression is regulated, and may act by
      disrupting higher order chromatin structure. In normal cells, the competing
      activities of two enzyme classes, the histone acetyl transferases (HATs) and
      histone deacetylases (HDACs), result in cell-specific patterns of gene
      expression. Aberrant patterns of histone acetylation have been linked to cancer,
      and natural and synthetic HDAC inhibitors (HDAIs) have shown antiproliferative
      effects on tumor cells in culture. Thus, there has been an increasing interest in
      histone deacetylase inhibitors as novel anticancer agents, with clinical
      investigation underway for several molecules. This review summarizes recent
      progress in the development of new HDAIs and their reported activities.

PMID- 12197308
TI  - Recent advances in the development of small molecule inhibitors of PTP1B for the
      treatment of insulin resistance and type 2 diabetes.
AB  - Protein tyrosine phosphatases (PTPs) are a large family of diverse molecules that
      play an important role in both activating and attenuating a wide variety of
      cellular responses. One of these phosphatases, protein tyrosine phosphatase 1B
      (PTP1B), is clearly involved in attenuating insulin signaling, and much effort
      has been devoted towards the development of inhibitors of this enzyme as a
      therapeutic approach to treat insulin resistance and type 2 diabetes. This review
      will focus on recent advances in the development of small molecule inhibitors for
      PTP1B and the challenges for generating selective molecules. This review is
      largely limited to papers published within the last two years, since a review on
      this subject was published recently in this journal.

PMID- 12197309
TI  - Recent advances in the development of gamma-secretase inhibitors.
AB  - Alzheimer's disease is a neurodegenerative disorder that exerts a huge
      psychological and social toll in modern societies. The current hypothesis for the
      cause of this illness is that it is the result of aberrant production of beta
      amyloid (A beta) and plaque deposition in the brain of affected individuals. New
      therapeutic interventions seek to stop or even reverse the course of the disease
      by inhibiting this aggregation or reducing A beta formation. The use of
      inhibitors of gamma-secretase, a key enzyme in the production of A beta, is
      currently undergoing preclinical and clinical evaluation. Small molecule
      inhibitors which demonstrate efficacy in reducing A beta burden in mice have thus
      been recently discovered. This review summarizes the development of such
      inhibitors in light of our current understanding of the function of gamma
      secretase. It also provides an evaluation of the therapeutic potential for this
      class of compounds with the recent discovery of other biochemical pathways
      associated with gamma-secretase, such as Notch signaling.

PMID- 12197310
TI  - Drug discovery and development using chemical genomics.
AB  - Now that the human genome is completely sequenced, it is important to convert
      this wealth of knowledge to therapeutic drugs. It is documented that there are
      approximately 30,000 genes in the human genome that may code for approximately
      100,000 proteins. Traditionally, the drug development process starts with a
      protein target, taking approximately eight to ten years for a drug to pass all
      the critical steps of testing before reaching the market. If this situation
      continues it will take several decades before all potential drug targets are
      tested and developed. Chemical genomics is a new paradigm in which chemistry is
      utilized early in the development process along with other tools such as
      genomics, proteomics, combinatorial chemistry and cell-based screening to
      accelerate the drug development process. Utilizing chemical genomics not only
      reduces the risk of drug failure but it can increase the number of potential
      targets for drug development.

PMID- 12197311
TI  - Chemical genomics: bridging the gap between the proteome and therapeutics.
AB  - Technical advances in the areas of DNA sequencing and bioinformatics in the past
      decade have led to the industrialization of the gene discovery process and the
      sequencing of the human genome. This sequence now provides a wealth of potential
      targets for the development of new therapeutics to treat human diseases. New
      technologies are now required to validate the roles that these genes play in
      human diseases and to discover new drugs at the scale and scope of the genome.
      This review describes the role that genomics has played in the discovery of
      disease targets and the opportunity that chemical genomics offers to validate
      these targets and discover small molecule ligands through an industrialized
      process that complements the genome.

PMID- 12197312
TI  - Guiding molecules towards drug-likeness.
AB  - This review discusses computational methods for the prediction of drug-likeness.
      The coverage of published works include the assessment of historical practices of
      lead generation and optimization, surveys of the properties of known drugs and
      their constituent fragments and scaffolds, methods for delineating drug space,
      optimization techniques for simultaneously enhancing multiple properties and drug
      like characteristics, similarity metrics and the application of more advanced
      pattern recognition algorithms for the prediction of drug-likeness. Areas which
      could be improved in this field are the scope of the datasets used to build
      models, the chemical interpretability of models, the use of multivariate
      optimization methods for drug design and the application of underappreciated
      statistical methods proven to work in other fields.

PMID- 12197313
TI  - Designing selective COX-2 inhibitors: molecular modeling approaches.
AB  - Molecular modeling approaches have been successfully used to gain insight into
      the molecular mechanism of selective cyclooxygenase-2 (COX-2) inhibition. These
      approaches are based on X-ray structure data and results from structure-activity
      relationships and site-directed mutagenesis experiments. The recognition process
      of substrates and inhibitors by COX isoenzymes can be visualized by applying
      algorithms to describe local properties on the enzyme surface, thus allowing key
      differences in structure to be studied that may confer differential sensitivity
      to inhibitors. The virtual screening techniques for COX isoenzymes are rapidly
      improving, and the search for new selective COX-2 inhibitors has been stimulated
      by the tremendous success of meloxicam, celecoxib and rofecoxib in the
      pharmaceutical market and their potential use in new indications.

PMID- 12197314
TI  - Microsomal triglyceride transfer protein (MTP) inhibitors: discovery of
      clinically active inhibitors using high-throughput screening and parallel
      synthesis paradigms.
AB  - The inhibition of microsomal triglyceride transfer protein (MTP) blocks the
      hepatic secretion of very low density lipoproteins (VLDL) and the intestinal
      secretion of chylomicrons. Consequently, this mechanism provides a highly
      efficacious pharmacological target for the lowering of low density lipoprotein
      (LDL) cholesterol and reduction of postprandial lipemia. The combination of these
      effects could afford unprecedented benefit in the treatment of atherosclerosis
      and consequent cardiovascular disease. The promise of this therapeutic target has
      attracted widespread interest in the pharmaceutical industry. Independent efforts
      have yielded strikingly similar series of lipophilic amide inhibitors. The way in
      which the evolutionary paths of distinct inhibitor series have tended to converge
      through the course of robotics-assisted synthesis efforts is illustrated with
      candidates from Bristol-Myers Squibb and Pfizer. Hanging in the balance with the
      exceptional potency of the compounds presented are the potential adverse effects
      due to blockage of intestinal fat absorption and hepatic lipid secretion. Finding
      a degree of efficacy that can be safely tolerated defines the dilemma surrounding
      the advancement of these compounds to clinical practice.

PMID- 12197315
TI  - New developments in chemical library synthesis. Norbornenyl tags for use in phase
      switching, sequestration, capture-release and soluble support applications.
AB  - A new, general chemical library purification platform is reviewed. This platform
      makes broad use of (oxa)norbornenyl-tagged reactants, reagents, catalysts,
      sequestration-enabling reagents and scavengers, in combination with Grubbs
      catalyst-mediated ring-opening metathesis polymerization (ROMP) reactions as an
      in situ polymerization purification technique. Extensions of this platform
      involve the use of preformed ROMP supports in synthesis, and polystyrene
      supported Grubbs catalysts, which perform in a boomerang fashion.

PMID- 12197316
TI  - Recent advances in chemical library synthesis methodology.
AB  - The first part of this review highlights recent advances in polymer-supported
      reagents, catalysts, reactants and sequestrants. Particular attention is given to
      recent advances in polymer-supported oxidants, transition metal catalysts and
      polymer-supported reactants, including acyl groups, guanidinyl groups, alkyl
      groups and various classes of nucleophiles. This second part of the review
      highlights recent advances made in the areas of chemical tagging and phase
      trafficking techniques, all of which have enabled further advances in the
      methodology of solution-phase chemical library synthesis.

PMID- 12197317
TI  - Solid-phase compound library synthesis in drug design and development.
AB  - This article is a subjective review of the literature between December 2000 and
      January 2002 related to the solid-phase synthesis of compound libraries for drug
      discovery and development. Examples of libraries yielding active compounds across
      a range of biological targets are presented, together with synthetic details
      where this is deemed of sufficient note. Background to the biological target and
      any structure-activity relationship, which can be discerned within members of a
      library series, is also discussed. A brief overview of new developments in solid
      phase technology that is likely to impact upon drug discovery is also included.

PMID- 12197318
TI  - Membrane array technology for drug discovery.
AB  - Lipid membrane arrays are a new technology emerging at the interface of materials
      science and cell biology. A defining feature of the membrane array architecture
      is the naturally fluid and functional state of the lipid bilayer membrane, which
      is maintained in an array of discrete corrals on a solid substrate. Solid
      supported membrane arrays are beginning to find important applications in
      academic research. Recent developments in membrane array manufacturing are
      positioning this technology to make the transition into industrial drug discovery
      programs.

PMID- 12197319
TI  - Using X-ray crystallography in drug discovery.
AB  - One of the most dramatic benefits of using crystallography in drug discovery has
      been the development of the structure-based drug design (SBDD) cycle: structure,
      analysis, synthesis, testing and back to structure. This review covers recent
      examples of SBDD to illustrate how this design cycle has evolved from its early
      implementation. The dimension of the cycle has increased to include the
      consideration of structures related to the target, optimization of global drug
      parameters and binding affinity. Other technologies, such as combinatorial
      chemistry and virtual screening, have been integrated into the design cycle. In
      addition, novel new ways of directly using the crystal have been developed.

PMID- 12197320
TI  - Recent trends in microwave-assisted synthesis.
AB  - Microwave-assisted organic synthesis streamlines a wide variety of reactions that
      require thermal reaction conditions. The popularity of this method has made an
      impact among synthetic chemists, greatly increasing the productivity of many
      medicinal chemistry laboratories and allowing difficult synthetic transformations
      to be achieved under milder conditions. This field is rapidly growing, and a
      number of comprehensive accounts and significant achievements have been published
      recently. This review will focus on some emerging key areas.

PMID- 12197321
TI  - NMR-based approaches for lead discovery.
AB  - NMR methods have long been used for studying molecular interactions. In the last
      few years, various NMR approaches have been developed to aid lead discovery.
      These involve different NMR screening methods to identify initial compounds,
      which often bind only weakly (in the micro- to millimolar range) to the drug
      target. Intelligent and focused follow-up strategies enable the development of
      these compounds into potent, submicromolar drug-like inhibitors for use as leads
      in drug discovery projects. NMR can be used as both a remarkably reliable
      screening tool and a structural tool; thus, this technique has unique
      opportunities for lead discovery.

PMID- 12197322
TI  - Anaemia among young male workers in Alexandria, Egypt.
AB  - In a cross-sectional survey, we investigated exposure to and the presence of
      factors associated with anaemia, such as socioeconomic conditions, dietary
      habits, intestinal parasitic infections and lead among 355 young male workers (7
      19 years of age) employed in private workshops. Of the total study sample, 44.5%
      (158 participants) were found to be anaemic. The major risk factors for anaemia
      were multiple parasitic infection, high intensity of parasitic (Ascaris
      lumbricoides) infection and drinking tea soon after a meal. A significantly lower
      prevalence of anaemia was noted after Ramadan; it appeared to be the main factor
      associated with the presence or absence of anaemia and warrants further
      attention.

PMID- 12197323
TI  - Anaemia among Egyptian adolescents: prevalence and determinants.
AB  - We aimed to estimate the nationwide prevalence of anaemia among adolescents in
      Egypt and to study possible risk factors. A cross-sectional approach was used.
      Blood samples were collected from 1980 adolescents for haemoglobin estimation.
      The overall prevalence of anaemia was 46.6%, most of which was mild or moderate,
      with severe cases in less than 1.0% of the sample. Gender difference was almost
      nonexistent. A significant inverse relationship was observed between the level of
      anaemia and age (especially among boys), socioeconomic level and educational
      level. Anaemia was more prevalent in rural areas and in Upper (southern) Egypt.
      Anaemia is a major public health problem among Egyptian adolescents and wide
      scale public health education is warranted.

PMID- 12197324
TI  - Induction of leukaemia in chloramphenicol-treated toads.
AB  - Chloramphenicol has been associated with the development of aplastic anaemia. As
      it is still widely used in Egypt, we studied its effect on 100 Egyptian toads
      (Bufo regularis) given a dose of chloramphenicol of 5 mg/40 g body weight for 12
      weeks. We found it induced numerous, severe ultrastructural changes in almost all
      types of leukocytes. These changes were similar to those induced by the chemical
      carcinogen 7,12-dimethylbenz(a)anthracene in 100 toads used as the carcinogen
      control group, and similar to those in leukocytes reported in humans with
      leukaemia. We recommend regulations be applied on the use of this antibiotic in
      countries where it is still widely used.

PMID- 12197325
TI  - Diabetic ketoacidosis in southern Jordan: five-year experience.
AB  - All cases of diabetic ketoacidosis admitted to Prince Zaid Hospital between 1993
      and 1997 were analysed for precipitating causes and outcome. Of 167 cases, 89
      were male and 78 female, with a mean age of 38 years. It was the initial
      presentation of diabetes mellitus in 21% of the patients. Infection and
      noncompliance were the leading precipitating causes but no cause was found in 14%
      of the patients. The mortality rate was 4.8%. Educating the public and patients
      about diabetic complications and therapy is the key to prevention of diabetic
      ketoacidosis.

PMID- 12197326
TI  - Prevalence of diabetes mellitus and impaired glucose tolerance in a rural
      Palestinian population.
AB  - The prevalence of diabetes mellitus and impaired glucose tolerance was
      investigated in a cross-sectional population-based study in a rural Palestinian
      population of 500 females and males aged 30-65 years. The prevalence of diabetes
      was 9.6% and 10.0% in females and males respectively. The prevalence of impaired
      glucose tolerance was 8.6%; 10.3% in females, 6.2% in males. The prevalence of
      total glucose intolerance (diabetes mellitus + impaired glucose tolerance) was
      18.4%. Our study provides the first baseline data on diabetes mellitus and
      impaired glucose tolerance in Palestine. The results indicate a high prevalence
      of glucose intolerance, information that is essential for the implementation of
      national planning and service provision.

PMID- 12197327
TI  - Study of cardiovascular disease risk factors among urban schoolchildren in
      Sousse, Tunisia.
AB  - To assess the risk to Tunisian children of cardiovascular diseases (CVD), we
      undertook an epidemiological survey of 1569 urban schoolchildren from Sousse.
      Prevalence rates for the following CVD risk factors were determined:
      hypertension, hypercholesterolaemia and other lipid disorders, obesity and
      tobacco consumption. Hypertension and hypertriglyceridaemia showed no
      statistically significant difference by sex. Hypercholesterolaemia, high levels
      of low-density lipoprotein cholesterol and obesity were all significantly higher
      for girls than boys. Smoking was significantly higher among boys. The relatively
      low CVD risk factor profile of Tunisian schoolchildren should be encouraged in
      adulthood and a school heart health programme should be established.

PMID- 12197328
TI  - Predictive models for mortality and length of hospital stay in an Egyptian burns
      centre.
AB  - Our aim was to obtain a statistical profile of survivors and deaths among burn
      victims and to develop predictive models for mortality and length of hospital
      stay. All patients admitted to the Burns Unit of Alexandria Main University
      Hospital over a 1-year period were included. Of 533 cases, mean length of
      hospital stay was 15.5 +/- 21.6 days and the mortality rate was 33%. Total
      surface area burnt, inhalation burns, age, sex, depth and degree of burn wounds
      were the significant independent predictors of mortality in multiple logistic
      regression analysis. The significant independent predictors of the length of
      hospital stay were clothing ignition, total surface area burnt, sex, degree and
      depth of burn and inhalation burns.

PMID- 12197329
TI  - DNA proliferative index as a marker in Iraqi aneuploid mammary carcinoma.
AB  - This study estimated nuclear DNA ploidy and DNA proliferative indices (PI) in
      mammary ductal carcinomas from 120 Iraqi female patients. Of the examined
      specimens, 82.7% were aneuploid. DNA ploidy correlated significantly with
      histological grade and estrogen receptor content of the primary neoplasm. In
      aneuploid carcinomas, high PI showed a clearer association than aneuploidy with
      menopausal status and progesterone receptor content of the tumour. PI and
      percentage aneuploidy were higher in larger tumours; nodal status showed no
      association with these cytometric findings. Using PI, patients classified as
      having Auer aneuploid carcinomas can be divided into subsets with different
      tumour characteristics, thus improving the selection of those whose high risk,
      node-negative presentation makes them candidates for adjuvant systemic therapy.

PMID- 12197330
TI  - Clinical performance of intrauterine device TCu-380 A in Benghazi, Libyan Arab
      Jamahiriya.
AB  - The study examined the reproductive and health profile of Benghazi women using
      intrauterine contraceptive devices (IUDs) and evaluated one such device, the TCu
      380 A. An historical longitudinal study was carried out using data from the
      Fertility Regulation Clinic, Keish Polyclinic, Benghazi. The subjects were 457
      women registered for TCu-380 A insertion between 1995 and 1998, who had been
      under follow-up for at least 6 months. The majority were Libyan (87.8%), aged 20
      29 years (63.4%), of parity 1-6 (67.1%), non-lactating (64.3%) and with normal
      delivery at last conception (95.1%). Half had a chronic disease. The cumulative
      36-month follow-up of those using TCu-380 A revealed an effectiveness rate of
      99.8%, a continuation rate of 96.1% and complications in 3.5%. TCu-380 A appears
      to be an effective, durable and safe IUD.

PMID- 12197331
TI  - Ultrasonography versus radiography in the diagnosis of maxillary sinusitis.
AB  - Water's view plain film radiography was compared with ultrasonography in the
      diagnosis of acute maxillary sinusitis in 50 patients at the Radiology Department
      of King Hussein Medical Centre in Jordan with clinical diagnosis of acute
      sinusitis. Ultrasound showed 100% concordance with plain radiographs reported as
      showing complete opacifications or an air fluid level, the only reliable plain
      film indicator of an inflamed antrum. We conclude that ultrasonography, which is
      non-ionizing, can provide an alternative to plain radiography in the initial
      investigation of maxillary sinusitis.

PMID- 12197332
TI  - Noncommunicable diseases among the Bahraini population: a review.
AB  - The review investigates changes in the morbidity and mortality due to
      noncommunicable diseases in the Bahraini population and looks at the conditions
      which may have contributed to them in the 1980s and 1990s. Data were extracted
      from the Ministry of Health annual health reports and the 1981 and 1991 censuses
      and other relevant published papers. Government strategies for the control of
      noncommunicable diseases and the promotion of healthy lifestyles are outlined.

PMID- 12197333
TI  - Review of leprosy cases in Benghazi, Libyan Arab Jamahiriya, 1994-98.
AB  - A descriptive study was conducted using case records from the Leprosy Clinic,
      Benghazi for the period 1994-98. A constant decline in the number of leprosy
      cases registered for multidrug treatment (MDT) was observed, from 18 in 1994 to 4
      in 1998. The ratio of multibacillary to paucibacillary cases was 1.3:1. Most of
      the patients were young male adults who were socially and economically
      productive. An hypopigmented patch was the most common lesion present on easily
      accessible sites. Early registration, compliance with MDT and follow-up will
      enhance the cure rate and lead to a reduction in disability rates. Despite
      elimination surveillance for new leprosy cases is essential.

PMID- 12197334
TI  - HIV infection in patients with tuberculosis in Baghdad (1996-98).
AB  - A three-staged prospective study involving 430 patients with tuberculosis was
      conducted at the Tuberculosis Institute, Baghdad during 1996-98. Of the 430
      patients, 270 were males, 370 patients were diagnosed as pulmonary tuberculosis
      and 60 patients had extrapulmonary tuberculosis. Considering some risk factors
      for human immunodeficiency virus (HIV) infection, 11 patients had tattoos, 13
      were prisoners and 5 were barbers. All the patients were tested for HIV infection
      and all were negative.

PMID- 12197335
TI  - Antibiotic resistance of Moroccan strains of Salmonella enteritidis isolated
      between 1996 and 1997.
AB  - Antimicrobial resistance is a worldwide problem. The antibiotic resistance of
      Moroccan strains of Salmonella enteritidis was investigated from 1996 to 1997. A
      total of 51 strains were collected within this period, 31 derived from human
      sources and 20 from food. Of the 31 human strains, 10 were resistant to
      antibiotics; 4 were resistant to two or more antibiotics. Of the 20 food strains,
      11 were resistant to antibiotics; 6 were resistant to two or more antibiotics.
      The results are similar to those obtained from strains isolated from other
      Mediterranean countries.

PMID- 12197337
TI  - Gallstone ileus in the Jordanian Royal Medical Services in a 10-year period.
AB  - Six patients (5 women and 1 man, with a median age of 71 years) were operated on
      for gallstone ileus in the 10-year period 1988-98. The diagnosis was made before
      operation in 2 patients. The obstructing stones were located in the terminal
      ileum in 3 patients and in the proximal ileum or jejunum in 3 patients.
      Choledochoduodenal fistula was present in all patients. A single-stage procedure
      (removal of the impacted stone, fistula repair and cholecystectomy) was performed
      in 1 patient, enterolithotomy alone in 4 patients and resection of part of the
      intestine where the stone was impacted with primary anastomosis performed in 1
      patient. In the postoperative period, 2 patients developed infection of the wound
      and 2 patients developed deep vein thrombosis; 1 of these died of pulmonary
      embolism.

PMID- 12197336
TI  - Hepatitis B surface antigen and anti-hepatitis C antibodies among blood donors in
      the Islamic Republic of Iran.
AB  - We determined the prevalence rate of hepatitis B surface antigen (HBsAg) and anti
      hepatitis C virus antibodies (anti-HCV) among 7897 healthy voluntary blood donors
      in Shiraz, Islamic Republic of Iran. Sera were examined for HBsAg and anti-HCV
      antibodies using a second-generation enzyme-linked immunosorbent assay. Positive
      sera for HBsAg were found in 85 (1.07%) of the individuals and anti-HCV
      antibodies were found in 47 (0.59%). We compared our results with those of other
      studies and conclude that the prevalence rate of HBsAg in our area has decreased
      in the last 2 decades; from being an area of high prevalence, it is now one with
      moderate-to-low prevalence. Since there are few reports on the seroepidemiology
      of hepatitis C in the Islamic Republic of Iran, we could not assess the changes
      in prevalence of hepatitis C.

PMID- 12197338
TI  - Incidence of Rhesus isoimmunization in Rhesus-negative mothers in Ramadi, Iraq,
      in the mid-1990s.
AB  - This work was carried out in Ramadi, Iraq over the period 1993 to 1997. Of 487
      rhesus (Rh)-negative mothers tested and followed up, 172 were primigravida, 1.7%
      of whom were Rh-isoimmunized. The frequency of isoimmunization increased with
      increasing number of pregnancies (4.9% for second pregnancies to 45.4% for fifth
      pregnancies). Comparison of our results with other earlier studies shows that the
      incidence of Rh-isoimmunization in our study was considerably greater than the
      others.

PMID- 12197339
TI  - Who uses the emergency room services?
AB  - This study aimed to clarify whether patients attending an emergency room
      generally had non-urgent problems. A study was made of 2841 patients attending
      the emergency room of Prince Zaid Ben Al-Hussein military hospital (south Jordan)
      over a 1-month period using data from the registration book. Patients were
      classified into four classes of urgency (life-threatening, urgent, non-urgent,
      trivial). The attendees were mainly children (26.4%). The admission rate was 3.2%
      and non-urgent conditions accounted for 91% of cases. Much of the use of
      emergency services was found to be inappropriate, a situation which should be
      changed.

PMID- 12197340
TI  - Pulmonary alveolar microlithiasis: an overlooked disease in Iraq.

PMID- 12197341
TI  - Tuberculous abscesses of the quadriceps femoris muscle without osseous
      involvement.

PMID- 12197342
TI  - Evaluation of the routine hepatitis B immunization programme in Palestine, 1996.
AB  - The objectives of this study were to evaluate routine hepatitis B immunization in
      Palestine. Blood samples of 119 children (89 fully immunized and 30 non
      immunized) were analysed. The protective antibody levels among immunized children
      were greater than the non-immunized children. Antibody levels among the immunized
      children were lower in the older age group (> 36 months), but no sex differences
      in antibody level were apparent. Thus, hepatitis B immunization had an excellent
      impact on preventing hepatitis B transmission (85% preventive). The non
      responders constituted 14.6% of the sample, which is higher than other studies.

PMID- 12197343
TI  - Hepatic fibrosis due to fascioliasis and/or schistosomiasis in Abis 1 village,
      Egypt.
AB  - An epidemiological study of fascioliasis and/or schistosomiasis was conducted in
      Abis 1 village. Stool specimens were collected from 2492 individuals and
      examined. Fascioliasis, alone or combined with schistosomiasis, was more
      prevalent among children aged between 5 years and 15 years than in adults. Serum
      procollagen III peptide (PIIIP) levels were determined as an indicator of active
      fibrosis, and liver histopathology and ultrasonography used as indicators of
      established fibrosis. PIIIP levels were significantly higher in children than in
      adults, and in mixed infections than in fascioliasis alone. In adults, fibrosis
      around granulomata detected by histopathology and grade 3 periportal fibrosis
      detected by sonography were encountered more frequently in dual than in single
      infections.

PMID- 12197344
TI  - Childhood visceral leishmaniasis complicated by bacterial infections.
AB  - Bacterial superinfection is one of the major complications leading to death in
      patients with visceral leishmaniasis. We studied the frequency and type of
      bacterial infection in 54 patients admitted to hospital with visceral
      leishmaniasis. The patients were children who ranged in age from 3 1/2 months to
      7 years. Bacterial infections were found in 22 (41%) of the patients. Bacteria
      were isolated in patients with pneumonia, septicaemia, otitis media, urinary
      tract infections and skin infections. Enterobacteriaceae were the most common
      bacterial agents isolated. In infants with visceral leishmaniasis, fatal
      bacterial infections can be accompanied by nonspecific signs and symptoms. Thus,
      it is important to initiate antibiotic treatment early.

PMID- 12197345
TI  - Cutaneous leishmaniasis in the Libyan Arab Jamahiriya: a study of the Yafran
      area.
AB  - We studied 445 cases of cutaneous leishmaniasis in the Yafran area during the
      period February 1991 to December 1992. The highest incidence rates were recorded
      at the end of the transmission seasons in two peaks, one in November 1991 and the
      second in December 1992. The ratio of infected males to females was 1.85:1.00.
      The highest rate of infection was found among people 11-20 years of age. This
      indicates that the disease is not new in the Yafran area.

PMID- 12197346
TI  - Comparison between Toxoplasma gondii DNA and specific immunoglobulins during
      pregnancy.
AB  - Early diagnosis of toxoplasmosis in pregnant women can be of great help in early
      intervention and prevention of congenital disorders that usually lead to fetal
      death. The purpose of the present study was to evaluate nested PCR amplification
      of the B1 gene of Toxoplasma gondii before and after treatment and in comparison
      to serological follow-up during treatment. The efficiency of treatment on the
      bases of PCR detection of T. gondii DNA was statistically significant, while it
      was insignificant when anti-toxoplasma specific IgM and IgG antibodies were used.
      PCR detection of T. gondii DNA when performed on whole blood is a rapid,
      sensitive and specific diagnostic procedure and is a valuable tool for
      establishing the diagnosis of T. gondii infection in women before or during
      pregnancy.

PMID- 12197347
TI  - Detection of Cryptosporidium parvum antigen by co-agglutination test and ELISA.
AB  - Confirmation of the presence of Cryptosporidium in environmental samples is
      laborious, costly and often difficult. We report here a simple and economic slide
      agglutination test (co-agglutination test) for detecting cryptosporidial antigen
      in stool, serum and water. The results show that as a screening method co
      agglutination is clearly superior to enzyme-linked immunosorbent assay (ELISA)
      and modified Ziehl-Neelsen staining, although ELISA is more accurate. The co
      agglutination test is recommended for application as a new tool for detecting
      cryptosporidial antigen in large-scale epidemiological surveys.

PMID- 12197348
TI  - Coccidial infection in immunosuppressed mice: prophylaxis and treatment with
      dehydroepiandrosterone.
AB  - Cryptosporidiosis and toxoplasmosis are diseases caused by opportunistic
      coccidial parasites that can lead to life-threatening infection in
      immunocompromised patients. We evaluated dehydroepiandrosterone as prophylaxis
      and therapy in immunosuppressed mice infected with Cryptosporidium parvum and
      avirulent Toxoplasma gondii. Mice were infected with either Cryptosporidium
      oocysts or Toxoplasma cysts. Assessment was by mortality rates, parasitic counts
      and electron microscopic studies. Mortality rates were significantly reduced in
      all treated groups. A significant reduction in the cryptosporidial oocyst count
      in stool and intestinal villi and in Toxoplasma cysts in the brains of infected
      mice was observed in all the groups. The effect of the drug was greater when
      given prior to infection.

PMID- 12197349
TI  - Specific IgG avidity in acute and chronic human fascioliasis.
AB  - The detection of IgG avidity in sera is potentially useful in the diagnosis of
      acute and chronic infection. We studied IgG avidity in 31 patients with
      fascioliasis, with the aim of evaluating the clinical application of this test to
      confirm the diagnosis of incubating cases and to distinguish between acute and
      chronic cases. Of the 31 cases, 13 were incubating and had a mean avidity index
      of 57.28 +/- 5.79%. The 18 chronic cases had an avidity index of 68.80 +/- 8.92%.
      The difference was highly significant. We conclude that IgG avidity is a reliable
      means of identifying the stage of fascioliasis and suggest a cut-off point of
      59.90% to distinguish between acute and chronic infection.

PMID- 12197350
TI  - Effects of single-dose praziquantel on morbidity and mortality resulting from
      intestinal schistosomiasis.
AB  - The long-term effect of single-dose praziquantel on morbidity and mortality from
      Schistosoma mansoni was investigated in surveys in 1987 and 1994 in central
      Sudan. Prevalence of infection dropped from 53% to 34%, and intensity of
      infection (> or = 400 eggs/g of faeces) from 31% to 18%. There was a reduction in
      hepatomegaly and hepatosplenomegaly, although splenomegaly alone was unchanged.
      Prevalence of periportal fibrosis decreased from 14% to 10%. Endoscopic
      investigation of patients with fibrosis showed a reduction in oesophageal varices
      from 47% to 30%. Mortality due to bleeding varices was high (community-wide, up
      to 11/100 infected patients with bleeding). Thus praziquantel mass treatment can
      be spaced to a much longer period, reducing the expense of treatment, delivery
      and distribution.

PMID- 12197352
TI  - Antimalarials prescribing patterns in Gezira State: precepts and practices.
AB  - A longitudinal pharmacoepidemiological study on prescribing patterns of
      antimalarials was conducted in Gezira State, Sudan. Different core drug
      prescribing indicators were identified, measured and correlated. Chloroquine and
      quinine were the most frequently prescribed antimalaria drugs but in 44.7% of
      cases, the dosage was inappropriate and did not conform to standard regimens. Due
      to variable and unmonitored patterns of drug resistance, most medical
      practitioners in Sudan tend to follow their own protocols to treat severe cases
      of malaria rather than conforming to standard regimens. We attribute the
      emergence of a high rate of resistance to malaria chemotherapy to such practices.
      We recommend interventions to ensure rational prescribing, and call for the
      formulation of a national antimalarial drugs policy.

PMID- 12197351
TI  - Epidemiological study of heterophyiasis among humans in an area of Egypt.
AB  - We aimed to determine the prevalence and intensity of infection of heterophyiasis
      among inhabitants of El-Meaddeya, Egypt. A cross-sectional stool examination
      survey was performed on 430 randomly chosen households, comprising 2219
      individuals. The overall prevalence of parasitic infection was 84.7%. Ascariosis
      was the most common (67.6%), followed by trichuriosis (49.7%) and heterophyiasis
      (33.8%). The prevalence and intensity of infection of heterophyiasis were most
      common in people 15-45 years, and greater in females than males. The highest
      intensity of infection was detected among fishermen. Intrafamilial aggregation of
      cases of heterophyiasis was identified.

PMID- 12197353
TI  - Staphylococcus aureus as a paradigm of a persistent problem of bacterial multiple
      antibiotic resistance in Abha, Saudi Arabia.
AB  - We reviewed the microbiology laboratory records of Abha Maternity Hospital, Saudi
      Arabia for 1996 and 1998 to assess multiple antibiotic resistance, using
      Staphylococcus aureus as a paradigm. A total of 587 and 485 strains were isolated
      in 1996 and 1998 respectively. In 1996, over 60.0% were resistant to five of the
      nine antibiotics tested; in 1998, over 55.0% were resistant to six antibiotics.
      In both years, 71.0% were methicillin-resistant S. aureus. Over 85.0% of all
      strains were multiresistant. Although over 100 types of resistance patterns were
      detected, more than half of the strains displayed fewer than 15 types. The
      strains most frequently isolated were considered hospital strains, which
      accounted for most infections.

PMID- 12197354
TI  - Acute respiratory infections in primary health care centres in northern Saudi
      Arabia.
AB  - This study was carried out in the northern region of Saudi Arabia during 1419 AH
      (1998 AD). A random sample of 1200 prescriptions was analysed to determine the
      magnitude of factors associated with acute respiratory infections (ARI) and their
      treatment. ARI were diagnosed in more than one-third of the prescriptions
      analysed, of which upper respiratory infections accounted for 65.8%, and
      pneumonia less than 1%. The prevalence of ARI was significantly higher in urban
      areas, among children, among males and during the colder seasons of the year.
      Antibiotics were prescribed for 87.8% of patients. This study reinforces the need
      to implement forthwith the Saudi national programme for diagnosis and treatment
      of ARI.

PMID- 12197355
TI  - Ringworm of the scalp in primary-school children in Alexandria: infection and
      carriage.
AB  - A total of 510 children from a primary school in Alexandria were examined for
      tinea capitis, and samples were taken from their scalps. Specimens were examined
      by direct microscopy and were cultured. Diagnosis was by clinical and mycological
      findings. Clinical evidence of pediculosis capitis was found in 54.1% of
      children, more commonly in girls. Dermatophytes were isolated from 7.4% of scalp
      samples (2.9% confirmed cases, 4.5% carriers). A further 2% were suspected cases
      as they were negative by mycology. Most of the children were under 10 years and
      none was aware of having the infection. All isolates were identified as
      Trichophyton violaceum.

PMID- 12197356
TI  - Cost-effectiveness and efficacy of CHROMagar Candida medium in clinical
      specimens.
AB  - CHROMagar Candida is a new medium for the differential isolation and
      identification of certain clinically important Candida species. This study
      evaluated the cost-effectiveness of this medium compared with conventional
      methods. Thirty reference strains, 158 clinical specimens and 105 stock cultures
      were investigated. Specimens were cultured on CHROMagar Candida medium and on
      Sabouraud chloramphenicol agar. Identification was by conventional methods on
      Sabouraud agar and appearance of colonies on CHROMagar Candida medium. CHROMagar
      Candida correctly identified isolates of C. albicans, C. tropicalis and C.
      krusei. It was superior in detecting mixed cultures. A comparison of time and
      cost was carried out. CHROMagar Candida provides a simple, accurate and cost
      effective method for identifying some clinically important Candida species.

PMID- 12197357
TI  - Biochemical effects of vinyl chloride monomer on the liver of occupationally
      exposed workers.
AB  - We investigated the effects of vinyl chloride monomer exposure on the liver of 86
      workers by measuring beta-glucuronidase, arylsulfatase A, adenosine deaminase, 5'
      nucleotidase and routine liver function enzymes in the sera of the workers. In 21
      of them, three or more of these parameters were raised, with a significant
      decrease in the level of blood glutathione and a significant increase in the
      enzyme activity level of glutathione S-transferase. Of these 21 workers, 14 had
      fatty liver infiltration, 8 of whom were also suffering from liver enlargement.
      Also, 4 workers had liver enlargement without fatty infiltration and 3 had
      enlarged spleens. The study highlights the need for vigilance in environmental
      monitoring and medical surveillance of workers exposed to this chemical.

PMID- 12197358
TI  - [Oral health behavior in students in north Lebanon].
AB  - We conducted a study of the state of oral health among 600 twelve-year-old
      schoolchildren in North Lebanon. We assessed the range of behaviours linked to
      dental health: dental hygiene, eating habits, use of fluoride and use of dental
      health services. Half of the students brushed their teeth at least once a day.
      For 74% of the children, it was mainly their mothers who taught them how to brush
      their teeth. Toothbrushes and toothpaste were used by 75% of the children. About
      82% had heard of fluoride but only 58% understood its usefulness. Four out of
      five children drank sugared drinks on a daily basis and 83% said that they had
      never been to the dentist. The information can serve as a basis for the
      development and implementation of health promotion and education programmes for
      oral health within schools.

PMID- 12197359
TI  - Measurement of the mandibular dental arch in Baghdad patients.
AB  - We measured the dental arch of 220 Baghdad patients (120 females and 100 males)
      attending the University of Baghdad Dental Clinic. Alginate impressions were
      taken from which stone casts were made. Specified points were noted on the casts
      and length and width measurements were taken. We found that the length
      measurements were smaller than the width measurements indicating an ovoid shape
      of arch. Also, the size of male arches was greater than those of females.

PMID- 12197360
TI  - Oral health practices and dental caries among Libyan pupils, Benghazi (1993-94).
AB  - We investigated the oral health practices and prevalence of dental caries among
      Libyan pupils (6-12 years), by studying 389 boys and 373 girls selected randomly
      from 11 public primary schools in three different residential areas indicating
      different socioeconomic levels. In all, 321 (42.1%) pupils did not brush their
      teeth, with significant differences in the different areas. The prevalence of
      dental caries was 61.9%, with no significant sex difference. At 12 years, the
      decayed, missing and filled teeth index was 1.63, the average decay per child was
      1.26 and the prevalence of dental caries was 50%, but the filling needs met was
      0.01. Health education programmes to improve oral hygiene practices should be
      considered.

PMID- 12197361
TI  - A proposal for writing and appraising case reports.

PMID- 12197362
TI  - The maternity care data project.

PMID- 12197363
TI  - Assisted hatching in assisted reproduction.

PMID- 12197364
TI  - Enhancement of the perception of systemic pain in women with vulvar vestibulitis.
AB  - OBJECTIVE: The aim of this study was to determine whether the characteristics of
      systemic pain perception and anxiety differ between women with vulvar
      vestibulitis and healthy women. DESIGN: Case control study. SETTING: Tertiary
      care hospital. POPULATION: Forty-four women with vulvar vestibulitis and 41
      healthy women participated in the study. METHODS: First, the women's state and
      trait anxiety was evaluated. Thereafer, heat pain stimuli were applied to the
      women's forearm and the pain and unpleasantness thresholds, as well as magnitude
      estimation of perceived intensity and unpleasantness of suprathreshold stimuli,
      were assessed. Finally, blood pressure was measured before, during and after a
      heat stimulus of 46 degrees C. MAIN OUTCOME MEASURES: Pain threshold and
      suprathreshold, and anxiety levels of women with vulvar vestibulitis. RESULTS:
      Women with vulvar vestibulitis had a higher anxiety state (40.0 [12.8] vs 34.1
      [10.8], P = 0.044), a higher anxiety trait (42.1 [10.2] vs 35.6 [7.5], P =
      0.005), a lower pain threshold (42.2 degrees C [2.5] vs 43.6 degrees C [1.9], P =
      0.006), a lower unpleasantness threshold (40.2 degrees C [2.9] vs 41.7 degrees C
      [2.3], P = 0.023), a higher magnitude estimation of suprathreshold pain at 47
      degrees C (88.3 [14.9] vs 70.8 [14.9], P = 0.0001) and at 48 degrees C (96.1
      [7.3] vs 84.6 [14.8], P < 0.0001), a higher scoring of tonic pain perception
      (65.2 [17.3] vs 53.0 [18.6], P = 0.006) and a higher increase in systolic blood
      pressure during tonic pain stimuli (4.6 [9.6] vs -2.1 [8.7] mmHg, P = 0.005).
      CONCLUSION: Women with vulvar vestibulitis have an enhanced systemic pain
      perception and are more anxious.

PMID- 12197365
TI  - Microvascular changes in the peripheral microcirculation of women with chronic
      pelvic pain due to congestion.
AB  - OBJECTIVE: Pelvic venous congestion is a common finding in women with chronic
      pelvic pain. While the pathophysiology of this condition is poorly understood,
      there are clear indications that it involves vascular dysfunction. The present
      studies sought abnormalities in microvascular function in these patients. DESIGN:
      Prospective longitudinal study. SETTING: A teaching hospital tertiary referral.
      POPULATION: Eighteen women with pelvic congestion and 13 normal women. METHODS:
      Parameters of microcirculatory function were measured in the calves of women
      using venous congestion plethysmography during the midfollicular and midluteal
      phases of the menstrual cycle. The women with pelvic congestion were studied
      again after treatment for the condition. MAIN OUTCOME MEASURES: Isovolumetric
      venous pressure, microvascular filtration capacity and limb blood flow. RESULTS:
      Of the measured parameters of microvascular function, only isovolumetric venous
      pressure (Pvi) was significantly higher in women with congestion when compared to
      the controls during the same phase of the cycle. There were no menstrual cycle
      related differences in any of the other measured parameters in either patients or
      controls. Following successful treatment for the condition, values of Pvi in
      women with pelvic congestion were significantly reduced, achieving a level
      similar to that observed in the controls. CONCLUSION: The observed changes in Pvi
      suggest that this parameter is intimately associated with the pathophysiology of
      pelvic congestion. The increase in Pvi, without alterations in other measured
      microvascular parameters, may be attributable to systemic increases in
      postcapillary resistance secondary to neutrophil activation. These findings
      support the notion of systemic microvascular dysfunction in these women.

PMID- 12197366
TI  - A randomised, double-blind trial comparing raloxifene HCl and continuous combined
      hormone replacement therapy in postmenopausal women: effects on compliance and
      quality of life.
AB  - OBJECTIVE: To compare continuous combined hormone replacement therapy (ccHRT) and
      raloxifene with respect to compliance and quality of life, which were predefined
      secondary endpoints of a large, prospective study designed to investigate the
      uterine effects of both treatments. DESIGN: Double-blind, randomised controlled
      trial of six-month duration. SETTING: One hundred and twenty-nine gynaecology
      hospital departments, clinics or practices specialised in women's healthcare,
      located in Europe, South Africa and Israel. POPULATION: Healthy postmenopausal
      women (n = 1008). MAIN OUTCOME MEASURES: Changes in quality of life using the
      Women's Health Questionnaire (WHQ) and compliance using a compliance
      questionnaire and pill count. Adverse event and early discontinuation rates and
      satisfaction with treatment using a visual analogue scale (VAS). RESULTS: Women
      taking raloxifene reported greater satisfaction with their treatment as assessed
      on the VAS (P = 0.004), and a lower proportion, as compared with ccHRT, reported
      being worried by the treatment (9.6% vs 20.2%, P < 0.01). Women taking ccHRT
      reported greater deterioration in scores from the WHQ for depressed mood and
      menstrual symptoms than those taking raloxifene (P < 0.01). For memory, vasomotor
      symptoms and sexual behaviour, the ccHRT group reported significantly greater
      mean improvements (P < 0.05). Over half (58.8%) of those taking raloxifene
      noticed no effect, 37.7% felt better and 3.4% felt worse as measured using the
      compliance questionnaire. Fifty percent of the women taking ccHRT felt better,
      37.8% noticed no effect but over 10% felt worse. More women on raloxifene (94.6%)
      than on ccHRT (85.9%) reported that they were taking their double-blinded
      medication regularly (P < 0.01). CONCLUSIONS: A lower rate of adverse event
      related discontinuations, the lack of negative effects on quality of life and a
      smaller proportion of women being worried by the drug treatment were associated
      with higher treatment satisfaction and better compliance in postmenopausal women
      taking ccHRT or raloxifene.

PMID- 12197367
TI  - Effects of tibolone and continuous combined hormone replacement therapy on
      bleeding rates, quality of life and tolerability in postmenopausal women.
AB  - OBJECTIVE: To compare the effects of tibolone and conjugated equine oestrogens
      continuously combined with medroxyprogesterone acetate on bleeding rates, quality
      of life (QoL) and tolerability. DESIGN: A double-blind, randomised comparative
      trial. SETTING: Thirty-seven centres in six European countries. POPULATION: Five
      hundred and one postmenopausal women, under 65 years of age with an intact
      uterus. INTERVENTIONS: For 12 months, women received daily treatment with
      tibolone 2.5 mg (n = 250), or conjugated equine oestrogens 0.625 mg continuously
      combined with medroxyprogesterone acetate 5 mg (CEE-MPA, n = 251). MAIN OUTCOME
      MEASURES: The primary outcome was vaginal bleeding rate during cycles 4-6. The
      secondary outcomes were vaginal bleeding rate during cycles 1-3, 7-9 and 10-13,
      cumulative bleeding rate, QoL, wellbeing, climacteric symptoms, urogenital
      complaints and tolerability. RESULTS: Treatment with tibolone led to a
      significantly lower bleeding rate during cycles 4-6 compared with CEE-MPA (15.0%
      vs 26.9%; P = 0.004); there was a similar difference during cycles 1-3. Both
      treatments improved QoL, wellbeing, climacteric symptoms and urogenital
      complaints. By intent-to-treat analysis, tibolone significantly improved sexual
      drive, interest and/or performance, compared with CEE-MPA at 12 months (P =
      0.017). Although both treatments were well tolerated, there was a significantly
      lower incidence of breast tenderness with tibolone than CEE-MPA (2.4% vs 17.1%; P
      < 0.001). CONCLUSION: The vaginal bleeding rate during cycles 4-6 was
      significantly lower in women using tibolone. Both treatments improved QoL,
      wellbeing, climacteric symptoms and urogenital symptoms. Breast tenderness was
      significantly less frequent with tibolone.

PMID- 12197368
TI  - The risk of preterm delivery in women from different ethnic groups.
AB  - OBJECTIVE: To examine whether routinely measured variables explained the
      increased risk of preterm delivery in some UK ethnic groups. DESIGN: Cross
      sectional study of deliveries recorded in the Child Health Record System.
      SETTING: North Birmingham, UK. POPULATION: All North Birmingham women delivering
      singletons, 1994-1997 inclusive. METHOD: Logistic regression. MAIN OUTCOME
      MEASURES: Odds ratio (OR) and 95% confidence interval (CI) for preterm delivery,
      defined as less than 37 weeks, less than 34 weeks and less than 28 weeks,
      unadjusted and adjusted for maternal age, an area-based socio-economic status
      measure, and marital status, year of birth, fetal sex and past obstetric history.
      RESULTS: For Afro-Caribbean women, the ORs (95% CIs) were: for delivery less than
      37 weeks, 1.44 (1.26-1.64) unadjusted and 1.22 (1.07-1.41) adjusted; for delivery
      less than 34 weeks, 1.55 (1.25-1.92) unadjusted and 1.29 (1.02-1.61) adjusted;
      for delivery less than 28 weeks, 1.66 (1.08-2.55) unadjusted and 1.32 (0.84-2.06)
      adjusted. For African women, the risk of delivery less than 37 weeks was not
      significantly raised; for delivery less than 34 weeks, the OR (95% CI) was 1.88
      (0.99-3.58) unadjusted and 1.78 (0.93-3.40) adjusted; for delivery less than 28
      weeks, the OR (95% CI) was 4.02 (1.60-10.12) unadjusted and 4.10 (1.66-10.16)
      adjusted. In Afro-Caribbeans, deprivation and marital status explained the
      differences between the unadjusted and adjusted ORs. There was a linear relation
      between deprivation and preterm delivery for all ethnic groups, except for
      Asians. CONCLUSIONS: Factors associated with deprivation and marital status
      explain about half of the excess of preterm births in Afro-Caribbeans, but not
      Africans. The risk of preterm delivery might not be related to deprivation in
      Asians.

PMID- 12197369
TI  - Sterilisation during unplanned caesarean sections for women likely to have a
      completed family--should they be offered? Experience in a country with limited
      health resources.
AB  - OBJECTIVE: To determine if it is proper to give a woman of higher parity who
      needs at short notice a caesarean section the option of a tubal ligation. DESIGN:
      Retrospective study. SETTING: Maternity unit of a tertiary hospital in Bulawayo,
      Zimbabwe. POPULATION: Women of higher parity who were delivered by an emergency
      caesarean section, by an elective caesarean section or vaginally and who had been
      asked or not asked whether they wanted a tubal ligation. METHODS: A postal
      questionnaire and visits to the participants. MAIN OUTCOME MEASURES: Satisfaction
      with (in)fertility after having had, or not had, the option of a tubal ligation
      with the last delivery. RESULTS: In women who had an emergency caesarean section
      and who were successfully followed up, 301/418 (72.0%) had been offered a tubal
      ligation and 241/301 (80.1%) accepted. Of the 301 women, 269 (89.4%) were happy
      with the outcome. Thirty-two women were unhappy (of whom 6 had tubal ligation, 24
      had declined a sterilisation and in 2 cases the doctor forgot to do the
      sterilisation). Of the 117/418 women not offered a tubal ligation, 75/117 (64.1%)
      regretted not having had one. The relative risk of being unhappy with the
      consequences of not being offered tubal ligation compared with being given this
      option was 6.0 (95% CI 4.2-8.6, P < 0.001). Tubal ligations performed during
      emergency caesarean sections had no higher regret rate (2.5%) in this setting
      than those performed during elective caesarean sections (3.2%) and not much
      higher than postpartum sterilizations (0.5%). Women who did not have a tubal
      ligation during an emergency caesarean section regretted this (56.4%)
      significantly more often than women who did not have a tubal ligation with an
      elective caesarean section (34.6%) or after vaginal delivery (45.0%) (P < 0.01
      and P < 0.02, respectively). CONCLUSIONS: We found no evidence that the need to
      take an urgent decision resulted in more regret following tubal ligation. Women
      were far more likely to regret declining a tubal ligation (40%) than regret
      accepting one (2.5%). In this setting, some women are more likely to die of the
      next pregnancy than to regret an emergency tubal ligation.

PMID- 12197370
TI  - Vitamin D deficiency in pregnant women from a non-European ethnic minority
      population--an interventional study.
AB  - OBJECTIVE: To determine the vitamin D status of pregnant women from non-European
      ethnic minorities in South Wales. DESIGN: Prospective study. SETTING: Llandough
      Hospital, Cardiff, South Wales. SAMPLE: One hundred and sixty pregnant women from
      a non-European ethnic minority population in South Wales. METHODS: Biochemical
      screening of vitamin D status was carried out at the first antenatal visit. Women
      found to be deficient in vitamin D were subsequently supplemented and vitamin D
      status was rechecked at delivery. MAIN OUTCOME MEASURE: Vitamin D status at
      delivery. RESULTS: Eighty of 160 women had a vitamin D level below 8 ng/mL at
      their first antenatal visit and were treated with oral vitamin D. Factors that
      could influence vitamin D status such as religion, fluency in English and
      dressing habits did not appear to have any effect, although a higher proportion
      of women who had lived in Britain for longer than three years had subnormal
      vitamin D levels. In 58 of those checked at delivery, the mean plasma vitamin D
      level increased from 6 to 11 ng/mL although the mean parathyroid hormone level
      was unchanged. CONCLUSION: In view of the high incidence of subnormal vitamin D
      levels in women from ethnic minorities, we recommend biochemical screening of
      these women in early pregnancy, with subsequent supplementation where indicated.

PMID- 12197371
TI  - Maternal smoking during pregnancy and nicotine and cotinine concentrations in
      maternal and neonatal hair.
AB  - OBJECTIVE: Conflicting data have been reported in the association between
      maternal smoking and adverse effects during pregnancy and in neonates. Some
      studies, conducted on a limited number of patients have evaluated maternal
      consumption and fetal exposure by measuring nicotine and cotinine in the hair.
      Our aims were to evaluate the relationship among maternal cigarette consumption,
      fetal smoking exposure and outcome of pregnancy in a population of pregnant women
      who smoked. DESIGN: Mothers smoking during pregnancy were included at their first
      prenatal visit and followed prospectively. Maternal data (demographic variables,
      obstetrical history and cigarette consumption), neonatal data and birth
      indicators (number of weeks of gestation, type of delivery, weight) were
      collected. Hair samples from the mothers and the babies were collected at birth.
      SETTING: The present study was conducted in the Department of Obstetrics of the
      University Hospital Robert Debre in Paris. POPULATION: A total of 254 women
      smokers were included in the study and 182 mother/neonate pairs were analyzed
      after exclusion of 50 babies whose hair samples were inadequate and 22 for
      various other reasons. METHODS: Nicotine and cotinine concentrations in the
      maternal and neonatal hair were measured at birth by radio-immunoassay. MAIN
      OUTCOME MEASURES: Cigarette consumption was based on self reporting and
      quantified each trimester. It was expressed more precisely during the third
      trimester by the mean number per cigarette per day. Nicotine and cotinine
      concentrations in the maternal and neonatal hair at birth were also analysed.
      RESULTS: Nicotine and cotinine concentrations in maternal hair were associated
      with cigarette consumption during the third trimester of pregnancy (P < 0.003 and
      P < 0.01, respectively). In neonates, only cotinine concentrations were
      associated to maternal cigarette consumption (P < 0.0001). This association
      remained significant in a multivariate analysis, which included maternal cotinine
      hair concentrations and the ethnic group. CONCLUSIONS: Our results have shown a
      strong relationship between maternal cigarette consumption and fetal exposure to
      smoking measured by cotinine concentrations in neonatal hair. Further studies are
      required to look for associations between fetal exposure and adverse pregnancy
      outcome.

PMID- 12197372
TI  - Cystic fibrosis and pregnancy. Report from French data (1980-1999).
AB  - OBJECTIVE: To study the consequences of pregnancy on women affected by cystic
      fibrosis and to clarify the impact of the disease on maternal and newborn health.
      DESIGN: Retrospective study. SETTING: Pregnancy survey from the French Cystic
      Fibrosis Registry. POPULATION: Women with cystic fibrosis having a pregnancy
      between 1980 and 1999. METHODS: During the 1980-1999 period, 90 pregnancies in 80
      French female patients were registered in the pregnancy survey of the French
      Cystic Fibrosis Registry. General and clinical data before pregnancy were noted.
      Outcome of the pregnancy was described. Variations of pulmonary function and body
      weight during pregnancy were evaluated. Comparison between a group of pregnant
      women and a group of non-pregnant cystic fibrotic women of same age and genotype,
      followed in the same care centre network, was made. MAIN OUTCOME MEASURES:
      Spirometric and nutritional parameters, vital status and perinatal health
      indicators. RESULTS: The outcome was identified for 75 cases: 64 delivered babies
      (45 at term and 10 prematurely, prematurity rate: 18%), 10 abortions (five
      spontaneous and five therapeutic or medical), and one maternal death during
      pregnancy. The proportion of newborns with low weight was 29.8%. Mean maternal
      weight gain during pregnancy was 5.5 kg. Four affected children were diagnosed
      after birth. A decline in the forced expiratory volume in one second (FEV1) and
      forced vital capacity was observed between the beginning of pregnancy and the
      year following the delivery. However, no significant difference was found when
      comparing the variation in the pulmonary function during pregnancy between cases
      and controls. Moreover, the pulmonary status before pregnancy was better than the
      status of non-pregnant women. Among 12 deaths recorded after pregnancy, only
      three happened in the year following the pregnancy. All three women had an FEV1 <
      50% before pregnancy. CONCLUSION: Pregnancy only has a slight adverse effect on
      maternal health if the women are in good general condition before starting
      pregnancy. Women with a better health status are more inclined to initiate and
      successfully complete a pregnancy. Complete collaboration between cystic fibrosis
      practitioners and obstetricians should be observed to allow women to deliver
      children in the best conditions.

PMID- 12197373
TI  - Charts of fetal size: limb bones.
AB  - OBJECTIVE: To construct new size charts for all fetal limb bones. DESIGN: A
      prospective, cross sectional study. SETTING: Ultrasound department of a large
      hospital. SAMPLE: 663 fetuses scanned once only for the purpose of the study at
      gestations between 12 and 42 weeks. METHODS: Centiles were estimated by combining
      separate regression models fitted to the mean and standard deviation, assuming
      that the measurements have a normal distribution at each gestational age. MAIN
      OUTCOME MEASURES: Determination of fetal limb lengths from 12 to 42 weeks of
      gestation. RESULTS: Size charts for fetal bones (radius, ulna, humerus, tibia,
      fibula, femur and foot) are presented and compared with previously published
      data. CONCLUSIONS: We present new size charts for fetal limb bones which take
      into consideration the increasing variability with gestational age. We have
      compared these charts with other published data; the differences seen may be
      largely due to methodological differences. As standards for fetal head and
      abdominal measurements have been published from the same population, we suggest
      that the use of the new charts may facilitate prenatal diagnosis of skeletal
      dysplasias.

PMID- 12197375
TI  - Active labour is associated with increased oxidisibility of serum lipids ex vivo.
AB  - OBJECTIVE: As a first step towards evaluating the role of oxidative stress in the
      process of labour, we tested whether term labour is associated with increased
      oxidisibility of maternal serum lipids. DESIGN: A controlled prospective study.
      SETTING: Tertiary care centre. POPULATION: Twenty healthy women in active labour
      and 20 healthy pregnant women not in labour (controls) matched for maternal and
      gestational age. METHODS: Venous blood was drawn from women in both groups. Serum
      levels of lipid peroxidation products and the kinetics of copper-induced
      oxidation ex vivo were monitored spectroscopically at 37 degrees C by continuous
      recording of absorbance at 245 nm. MAIN OUTCOME MEASURES: Oxidative stress
      parameters. RESULTS: The initial optical density (OD) at 245 nm, attributed to
      preformed dienic hydroperoxides and 7-keto-cholesterol (main products of lipid
      peroxidation), was higher in the labouring group than in the controls (1.30 +/-
      0.11 vs 1.18 +/- 0.09, OD 245 nm, respectively, P < 0.001). The lag phase,
      reflecting resistance of serum lipids to oxidation, was significantly shorter in
      the labouring group than in the controls (43.2 +/- 1.4 vs 56.2 +/- 4.7 min,
      respectively, P = 0.01). CONCLUSION: High levels of serum hydroperoxides and
      decreased resistance of serum lipids to copper-induced peroxidation ex vivo
      suggest labour to be associated with high oxidative stress. Whether oxidative
      stress is involved in initiating the labour process or is consequent awaits
      further studies.

PMID- 12197374
TI  - Flow-mediated dilatation of the brachial artery in pregnancy at high altitude.
AB  - OBJECTIVE: Pregnancy at high altitude has been associated with increased
      prevalence of pre-eclampsia and reduced maternal oestrogen levels, factors that
      have been associated with endothelial dysfunction. The aim of this study was to
      examine the effect of high altitude (4370 m above sea level) on endothelial
      function during pregnancy as assessed by a non-invasive method. DESIGN: Cross
      sectional study. SETTING: Two maternity units providing routine antenatal care:
      one at high altitude (District General Hospital--IPSS in Cerro de Pasco, Peru)
      and one at sea level (Instituto Materno-Perinatal in Lima, Peru). POPULATION:
      Sixty pregnant women at 6-42 weeks of gestation resident at high altitude (Cerro
      de Pasco, Peru, 4370 m above sea level) and 54 at sea level (Lima, Peru).
      Comparisons were performed also in 11 and 14 non-pregnant women at each altitude,
      respectively. METHODS: Endothelial function was assessed by flow-mediated
      dilatation of the brachial artery using high-resolution ultrasound. MAIN OUTCOME
      MEASURES: Differences in flow mediated dilatation of the brachial artery in two
      groups of pregnant women, one at high altitude and one at sea level. RESULTS:
      Both at high altitude and sea level flow-mediated dilatation of the brachial
      artery increased in the first two trimesters to levels 32% higher than non
      pregnant controls. However, in the third trimester, flow-mediated dilatation of
      the brachial artery was lower than non-pregnant levels. Resting vessel size
      increased during pregnancy by 15% compared with non-pregnant controls at term,
      with no difference between the two populations at high and low altitude.
      Pregnancy at high altitude, compared with sea level, was associated with 59%
      lower baseline blood flow and 76% higher reactive hyperaemia. Similarly, non
      pregnant controls at high altitude compared with sea level demonstrated similar
      flow-mediated dilatation of the brachial artery and 40% lower resting blood flow
      of the brachial artery. However, the difference in reactive hyperaemia did not
      reach statistical significance. CONCLUSION: These data suggest that, during
      pregnancy at high altitude, endothelial function, as assessed by flow-mediated
      dilatation of the brachial artery, is not impaired.

PMID- 12197376
TI  - Alteration of anal sphincter morphology following vaginal delivery revealed by
      multiplanar anal endosonography.
AB  - OBJECTIVE: To assess morphologic change in the anal sphincters in the absence of
      endosonographic evidence of trauma after vaginal delivery. DESIGN: Prospective
      observational study. SETTING: District general hospital. POPULATION:
      Consecutively booked nulliparous pregnant women attending antenatal clinic.
      METHODS: All women were examined using three-dimensional anal endosonography,
      simple manometry and had questionnaire assessment of incontinence before and
      after delivery. MAIN OUTCOME MEASURES: Components of the anal canal were measured
      in the axial, sagittal and coronal planes and paired pre- and post-delivery
      examinations were compared. Any changes were related to changes in continence and
      anal canal manometry. RESULTS: Twenty-two women had a vaginal delivery and no
      endosonographic evidence of perineal trauma after delivery. After delivery, there
      was significant shortening of the length of the anterior external anal sphincter
      [EAS] (mean 21.7 vs 20.5 mm, P = 0.02) when measured in the sagittal plane, which
      increased in anterior angulation with respect to the axis of the anal canal (10
      degrees vs 13.8 degrees, P = 0.03). In the axial plane, no change was seen in the
      thickness of any of the sphincter components after delivery. None of these
      morphologic changes correlated with changes in manometry or continence score.
      CONCLUSIONS: Anal sphincter morphology changes after an otherwise atraumatic
      vaginal delivery. This change does not correlate with any functional symptoms.

PMID- 12197378
TI  - High transduction efficiency of circulating first trimester fetal mesenchymal
      stem cells: potential targets for in utero ex vivo gene therapy.
AB  - We recently reported the existence of fetal mesenchymal stem cells in first
      trimester fetal blood. Here we demonstrate that fetal mesenchymal stem cells from
      as early as eight weeks of gestation can be retrovirally transduced with 99%
      efficiency without selection. Circulating fetal mesenchymal stem cells are known
      to readily expand and differentiate into multiple tissue types both in vitro and
      in vivo, and might be suitable vehicles for prenatal gene delivery. With advances
      in early fetal blood sampling techniques, we suggest that genetic disorders
      causing irreversible damage before birth could be treated in utero in the late
      first/early second trimester by genetically manipulated autologous fetal stem
      cells.

PMID- 12197377
TI  - Autofluorescence spectroscopy for the diagnosis of cervical intraepithelial
      neoplasia.
AB  - OBJECTIVE: To assess the feasibility of autofluorescence spectroscopy in the
      diagnosis of cervical intraepithelial neoplasia (CIN) using broadband light
      excitation. DESIGN: Feasibility study. SETTING: Colposcopy clinic of an
      university hospital. POPULATION: Sixty-eight patients at risk for CIN. METHODS:
      After excitation with a broadband light between 375 and 440 nm, spectral
      distribution of native tissue fluorescence (autofluorescence) was acquired from
      685 cervical sites for the localisation and differentiation of CIN, and compared
      with colposcopically directed biopsy and human papillomavirus (HPV) DNA testing.
      MAIN OUTCOME MEASURE: Detection of CIN. RESULTS: The evaluation of spectral
      measurements revealed significantly lower autofluorescence values for CIN 3
      lesions compared with normal tissue (P < 0.001), and compared with CIN 1 or CIN 2
      (P < 0.002). High grade CIN lesions (CIN 2/3) presented with a significant
      reduced autofluorescence compared with CIN 1 (P < 0.002). Patients with a
      positive HPV DNA testing showed a significantly lower autofluorescence than
      patients tested negative for HPV DNA (P < 0.05). Severe inflammation such as
      chronic cervicitis may lead to false positive results. CONCLUSIONS:
      Autofluorescence spectroscopy represents an interesting approach for the
      detection of cervical neoplasia. Using an excitation wavelength band between 375
      and 440 nm, significant differences between normal and precancerous lesions of
      the cervix can be seen.

PMID- 12197379
TI  - Administration of low molecular weight heparin within two hours before caesarean
      section increases the risk of wound haematoma.
AB  - A retrospective analysis of the relation between time interval from prophylactic
      administration of low molecular weight heparin (LMWH) to delivery and the
      occurrence of wound haematoma was performed in all women, who had a caesarean
      section in 1998. After administration of LMWH within 2 hours of surgery, the
      percentage of women with a wound haematoma was significantly larger (12% vs 3%).
      Multivariate regression analysis, including other risk factors for wound
      haematoma, indicated administration of LMWH within 2 hours prior to delivery as
      the only statistically significant factor, which influenced the development of
      wound haematoma (odds ratio = 5.3, 95% CI = 1.2-22.8).

PMID- 12197380
TI  - Low dose 25 mg oestradiol implants and 1 mg norethisterone as continuous combined
      hormone therapy: a prospective study.
AB  - The anxiety regarding no-bleed regimens is that breakthrough bleeding and
      endometrial hyperplasia may occur. We aimed to demonstrate that 25 mg oestradiol
      implants can be adequately opposed by a low dose of progestogen protecting
      against osteoporosis. Twenty-two patients were recruited to the study. The mean
      age was 62 years and body mass index of 26.5. Median oestradiol rose from 77
      pmol/L at baseline to 275 pmol/L at one year. Median endometrial thickness
      remained unchanged at 4 mm and only two women withdrew with bleeding problems.
      There was one case of proliferative endometrium at one year--all others samples
      were either atrophic or secretory. Lumbar bone density (L2-L4) rose significantly
      from 0.939 to 0.992 g/cm2 (6%, P = 0.005) and the total femoral density rose from
      0.872 to 0.890 g/cm2 (+2.1%). Bone formation markers increased significantly
      (serum type 1 procollagen C terminal peptide, P1CP = 112-114, P = 0.0376) and
      bone resorption fell (serum type 1 collagen C terminal telopeptide, 1CTP = 3.0
      2.9, P = 0.2863). E25 implants and low dose progestogen appear to avoid
      endometrial hyperplasia and bleeding problems while increasing bone density.

PMID- 12197382
TI  - Combined B-lynch suture with intrauterine balloon catheter triumphs over massive
      postpartum haemorrhage.

PMID- 12197381
TI  - Plasma exchange in a woman with thrombotic thrombocytopenic purpura or severe pre
      eclampsia.

PMID- 12197383
TI  - Partial hydatidiform mole following intracytoplasmic sperm injection and assisted
      zona hatching.

PMID- 12197384
TI  - [Induction of the anti-meningitis immunity with synthetic peptides. III.
      Immunoactive synthetic fragments of NspA protein from Neisseria meningitidis].
AB  - Four potentially immunoactive peptide fragments of the NspA protein from the
      outer membrane of the bacterium Neisseria meningitidis were synthesized in order
      to create a synthetic vaccine against the meningococcal infection by the
      serogroup B bacterium. Mice of various lines were immunized with the free
      peptides nonconjugated with a protein carrier. All the synthetic peptides were
      shown to induce the production of the antipeptide antibodies in mice. A peptide
      capable of inducing a decrease in the number of bacteria in blood and the
      protection of infected animals from death was found in the experiments on the
      protection of the animals infected with two strains of the Neisseria meningitidis
      serogroup B. The English version of the paper: Russian Journal of Bioorganic
      Chemistry, 2002, vol. 28, no. 4; see also http://www.maik.ru.

PMID- 12197385
TI  - [Isolation, biological properties, and spatial structure of an antibiotic
      loloatin A].
AB  - Peptide antibiotic with cyanolytic activity was isolated from the IGM52 strain of
      the Brevibacillus laterosporus Gram-positive spore-forming bacteria. By 1H NMR
      spectroscopy, this antibiotic was identified as loloatin A, a cyclic decapeptide
      cyclo(-Asn-Asp-Tyr-Val-Orn-Leu-DTyr-Pro-Phe-DPhe-). The spatial structure of
      loloatin A in solution was determined. The English version of the paper: Russian
      Journal of Bioorganic Chemistry, 2002, vol. 28, no. 4; see also
      http://www.maik.ru.

PMID- 12197386
TI  - [Key amino acid residues responsible for the color of green and yellow
      fluorescent proteins from the coral polyp Zoanthus].
AB  - Site-directed mutagenesis was used to study the structural basis of color
      diversity of fluorescent proteins by the example of two closely related proteins
      from one organism (coral polyp Zoanthus sp.), one of which produces green and the
      other, yellow fluorescence. As a result, the following conversions of emission
      colors were performed: from yellow to green, from yellow to a dual color (yellow
      and green), and from green to yellow. The saltatory character of the spectral
      transitions and the manifestation of the dual-color fluorescence suggest that
      chemically different fluorophores are responsible for the green and yellow
      fluorescence. The simultaneous presence of three residues, Gly63, Lys65, and
      Asp68, is necessary for the efficient formation of the yellow rather than green
      fluorophore. The English version of the paper: Russian Journal of Bioorganic
      Chemistry, 2002, vol. 28, no. 4; see also http://www.maik.ru.

PMID- 12197387
TI  - [Characterization of urokinase type plasminogen activator modified by
      phenylglyoxal].
AB  - A chemical modification of single-chain urokinase-type plasminogen activator (scu
      PA) with phenylglyoxal under mild conditions resulted in the scu-PA derivatives
      with various numbers of the modified Arg residues. The study of properties of the
      resulting derivatives demonstrated that the modification of 4-12 Arg residues did
      not cause any loss of the activator, fibrinolytic, and potential amidase
      activities of the activator. The scu-PA with four modified Arg residues was found
      to be the most stable derivative in human blood plasma; it causes a more
      efficient lysis of plasma clots than the native activator. Three of four modified
      Arg residues are supposed to be within the 178RRHRGGS184 cluster, which was
      localized in the superficial loop of the scu-PA globule and was shown to interact
      with the complementary series of negatively charged residues in the molecule of
      the main plasma inhibitor PAI-1. The neutralization of positively charged Arg
      residues in this cluster decreases the affinity of scu-PA and the double chain
      urokinase-type plasminogen activator for PAI-1, which results in an enhancement
      of the stability in plasma and the fibrinolytic efficiency of the activator. The
      English version of the paper: Russian Journal of Bioorganic Chemistry, 2002, vol.
      28, no. 4; see also http://www.maik.ru.

PMID- 12197389
TI  - [Synthesis of nucleotide derivatives containing 1-(4-(3-(trifluoromethyl)-3H
      diazirin-3-yl)benzamido)-2,3-propanediol for photoaffinity modification of
      proteins and nucleic acid].
AB  - 1-(4-(3-(Trifluoromethyl)-3H-diazirin-3-yl)benzamido)-3-O-(4,4'- dimethoxytrityl)
      2,3-propanediol phosphoramidite was synthesized and used as a modified unit in
      the automatic synthesis of oligodeoxyribonucleotides. Pentadecathymidylates with
      various numbers of 2,3-propanediol moieties substituted with
      aryl(trifluoromethyl)diazirinyl (ATFMD) were obtained, and the thermal stability
      of their duplexes with (dA)15 were studied. One ATFMD-propanediol residue was
      shown to reduce the thermal stability of the duplex by 8-9 degrees C. The
      irradiation of the ATFMD-containing duplexes by UV light with the wavelength of
      350 nm was found to cause the cross-linking reaction of the ATFMD-containing
      strand with the complementary strand and the formation of the cross-linked
      duplexes. The photomodification efficiency was independent of the oligonucleotide
      sequence, with each ATFMD group providing for 5% cross-linking. The irradiation
      of an ATFMD-containing duplex, a substrate of the HIV-1 integrase, in the
      presence of this enzyme resulted in the covalent DNA-protein complex. The
      oligonucleotides with the 1-(4-(3-(trifluoromethyl)-3H-diazirin-3-yl)benzamido)
      2,3-propanediol moiety in their chains can be used for the photoaffinity
      modification of both nucleic acids and proteins that recognize them. The English
      version of the paper: Russian Journal of Bioorganic Chemistry, 2002, vol. 28, no.
      4; see also http://www.maik.ru.

PMID- 12197388
TI  - [Theoretical study of antagonists and inhibitors of mammalian adenosine
      deaminase. I. Adenosine and its aza- and deaza-analogs].
AB  - Aza- and deazaanalogues of adenosine, including their 1-protonated forms (except
      for that of 1-deazaadenosine), were studied by computer computation to find a
      relationship between their molecular structures and substrate properties for the
      mammalian adenosine deaminase. The atomic charge distribution and maps of the
      electrostatic potential around their van der Waals molecular surface were
      calculated for these compounds using the ab initio STO-3G method. The
      conformational studies were carried out by the MM+ method of molecular mechanics.
      The mechanism that determines the substrate selectivity of mammalian adenosine
      deaminase is discussed. The English version of the paper: Russian Journal of
      Bioorganic Chemistry, 2002, vol. 28, no. 4; see also http://www.maik.ru.

PMID- 12197390
TI  - [Cleavage of RNA in a hybrid duplex by E. coli ribonuclease H. III. Substrate
      characteristics of hybrid duplexes of RNA and oligodeoxyribonucleotides
      containing a bleomycin A5 residue].
AB  - The effect of the bleomycin A5 residue linked to four-, eight-, and twelve-mer
      oligodeoxyribonucleotides on the substrate properties of their tandem and
      continuous (with or without unmodified octanucleotide effectors) hybrid duplexes
      was studied using E. coli RNase H. The bleomycin derivatives of
      oligodeoxyribonucleotides were shown to form hybrid duplexes with practically the
      same thermostability as those formed by unmodified oligodeoxyribonucleotides. The
      RNA in the bleomycin-containing hybrid duplexes is cleaved by the E. coli RNase
      H; however, the initial hydrolysis rate (v0) is 2.6-3.4-fold reduced for the
      continuous duplexes. In the case of tandem hybrid complexes, the effect of
      bleomycin on v0 was less pronounced. We hypothesized that steric factors play a
      key role in the bleomycin inhibition and effectors probably determine the
      substrate properties of such hybrid complexes. Of all the tandem systems studied,
      the RNA duplex with the bleomycin-containing tetranucleotide flanked with two
      effectors displayed the best substrate properties. The English version of the
      paper: Russian Journal of Bioorganic Chemistry, 2002, vol. 28, no. 4; see also
      http://www.maik.ru.

PMID- 12197391
TI  - [Enhancer activity of solitary long terminal repeat of the human endogenous
      retrovirus of the HERV-K family].
AB  - The transient expression of the luciferase reporter gene helped us to detect a
      tissue-specific enhancer activity of the solitary extraviral long terminal repeat
      (LTR) of the human endogenous retrovirus K (HERV-K). The LTR was previously
      mapped to the 19q13.2 locus. It contains a number of potential regulatory
      elements including TATA box, binding sites for some nuclear factors, and a
      polyadenylation signal. However, an analysis of the genomic sequences close to
      the LTR did not reveal any known genes or the expressing marker sequences (EST),
      whose functioning could be regulated by this LTR. The enhancer activity can be
      preserved in the solitary LTR due to its involvement in a long-range control of
      genome functioning or by the absence of functional disruptive mutations within
      the human-specific LTR, because it is of a relatively young evolutionary age. The
      English version of the paper: Russian Journal of Bioorganic Chemistry, 2002, vol.
      28, no. 4; see also http://www.maik.ru.

PMID- 12197392
TI  - [A new KIAA1245 gene family with or without HERV-K LTRs in their introns].
AB  - A transcript containing the long terminal repeat (LTR) and the sequence
      homologous to the KIAA1245 mRNA fragment were revealed among the transcribed LTRs
      of human endogenous viruses of the K family in normal and tumor tissues. Ten
      other sequences with a high level of homology to the KIAA1245 mRNA were found in
      the GenBank. The intron-exon structures were determined for all the sequences,
      and their exon sequences were compared. The comparison showed that they differ
      both in the extent of the exon homology and in the presence or absence of the
      HERV-K LTR in the third intron. The revealed sequences form a new gene family
      that comprises at least four subfamilies. Two of these subfamilies have the LTR,
      and the other two do not. We showed by PCR that the LTR was integrated into the
      introns after the divergence of the orangutan evolutionary branch from other
      hominoids but before the divergence of the gorilla branch, i.e., 8-13 million
      years ago. The English version of the paper: Russian Journal of Bioorganic
      Chemistry, 2002, vol. 28, no. 4; see also http://www.maik.ru.

PMID- 12197393
TI  - [Expression of ouabain-sensitive H+,K+-ATPase catalytic subunit gene in the rat
      epidermis].
AB  - A comparative localization of Na+,K(+)-ATPase and ouabain-sensitive H+,K(+)
      ATPase in rat skin was performed using in situ RNA hybridization and
      immunohistochemistry. Na+,K(+)-ATPase was predominantly detected in the basal
      layer of epithelium, whereas the ouabain-sensitive H+,K(+)-ATPase, in the
      granular and prickle cell layers. The genes of these ATPases are thus expressed
      in epithelial cells at different stages of their development. The hypothesis was
      advanced that the ouabain-sensitive H+,K(+)-ATPase is involved in maintaining the
      skin pH value. The probes specific to the mRNAs of the full-size alpha-subunit of
      the ouabain-sensitive H+,K(+)-ATPase and its truncated form were used to
      establish a similar distribution of both mRNA variants in skin. The English
      version of the paper: Russian Journal of Bioorganic Chemistry, 2002, vol. 28, no.
      4; see also http://www.maik.ru.

PMID- 12197394
TI  - [Synthesis of triads based on deuteroporphyrin IX, naphthoquinone, and aromatic
      amino acids].
AB  - Two triad systems were synthesized from deuteroporphyrin IX by tethering 1,4
      naphthoquinone derivatives and aromatic amino acids to its propionic groups using
      the method of mixed anhydrides. Physicochemical characteristics of the triads
      were studied, and the pi-electron systems of their chromophores were shown to
      interact. The English version of the paper: Russian Journal of Bioorganic
      Chemistry, 2002, vol. 28, no. 4; see also http://www.maik.ru.

PMID- 12197395
TI  - [Novel biologically active polymer of 3-(3,4-dihydroxyphenyl)glyceric acid from
      two types of the comphrey Symphytum asperum and S. caucasicvum (Boraginoceae)].
AB  - Two high-molecular water-soluble preparations with high anticomplement and
      antioxidant activity were isolated from the roots of Symphytum asperum and S.
      caucasicum. Their main chemical constituent was found to be poly[oxy-1-carboxy-2
      (3,4-dihydroxyphenyl)ethylene] according to IR and NMR spectroscopy. The English
      version of the paper: Russian Journal of Bioorganic Chemistry, 2002, vol. 28, no.
      4; see also http://www.maik.ru.

PMID- 12197396
TI  - [Chemical ribonucleases. 4. Analysis of the fragment structure of chemical
      ribonucleases based on 1,4-diazabicyclo[2.2.2]octane].
AB  - Artificial ribonucleases of the ABLkCm series were synthesized. They consist of a
      lipophilic alkyl radical (Et, n-C14H29, or C15H31) A, an "RNA-binding domain" B
      (bisquaternary salt of 1,4-diazabicyclo[2.2.2]octane), a "catalytic domain" Cm
      [histamine (C1) or histidine (C3) residue], and a "linker" Lk that joins the
      "domains" B and Cm [here, k is the number of methylene units (one or three) in
      the linker]. The effect of the "domain structure" on the catalytic properties of
      the chemical ribonucleases was analyzed using seven compounds of this series
      (ABL1C1, ABL3C1, ABL3C3, AC1, AB, BL2, and BL3C3). The catalytic activity of the
      compounds was assessed in the reaction of hydrolysis of the in vitro transcripts
      of human tRNA(Lys) and yeast tRNA(Asp) under physiological conditions. It was
      shown that only chemical ribonucleases that involve all the fragments of the
      ABLkCm construct can hydrolyze the substrate tRNA at a high rate (90% of tRNA is
      hydrolyzed for 10 h at 37 degrees C). The activity of the compounds is largely
      determined by the presence of a long lipophilic radical linked to 1,4
      diazabicyclo[2.2.2]octane and a long linker, which joins the RNA-hydrolyzing and
      RNA-binding fragments. The results indicate an important role of hydrophobic
      interactions in the acceleration of the RNA hydrolysis reaction. The English
      version of the paper: Russian Journal of Bioorganic Chemistry, 2002, vol. 28, no.
      4; see also http://www.maik.ru.

PMID- 12197398
TI  - [Nutritional support and tumor diseases].
AB  - The evidence of the use of artificial nutrition in the patients suffering from
      malignant disease is inconsistent due to ethics and possible support of malignant
      cells by supplemented substrates. On the contrary, tumor cachexia from various
      causes is one of the most frequent manifestation of tumor. The indications and
      composition of artificial nutrition in the intensive care of patients suffering
      from tumors are discussed owing to the therapy.

PMID- 12197397
TI  - [1H-NMR analysis of self association of an antibiotic actinocyl-bis(3
      dimethylaminopropylamine) in water solutions].
AB  - The self-association of the synthetic antibiotic actinocyl-bis(3
      dimethylaminopropylamine) was studied in aqueous solution by one- and two
      dimensional 1H NMR spectroscopy at 500 MHz. The two-dimensional homonuclear
      correlation NMR techniques (TOCSY and ROESY) were used to completely assign all
      the proton signals of the antibiotic and to quantitatively analyze the mutual
      arrangement of the antibiotic molecules in their aggregates. The concentration
      and temperature dependences of proton chemical shifts were used to determine the
      equilibrium constants and the thermodynamic parameters (delta H and delta S) of
      the self-association, as well as the limiting values of proton chemical shifts in
      associates. The experimental results were analyzed using both the indefinite
      noncooperative and cooperative models of the molecular self-association. The
      calculated value of the cooperativity coefficient (sigma approximately 1.1) for
      our synthetic antibiotic confirmed a substantially lower anticooperative effect
      at the aggregation of its molecules in comparison with that of the antitumor
      antibiotic actinomycin D (sigma approximately 1.5). We calculated the most
      favorable structure of the dimeric associate of the synthetic antibiotic in
      aqueous solution and found that, like in the actinomycin D dimer, the
      antiparallel orientation of the phenoxazone chromophore planes of interacting
      molecules is characteristic of its dimer. The English version of the paper:
      Russian Journal of Bioorganic Chemistry, 2002, vol. 28, no. 4; see also
      http://www.maik.ru.

PMID- 12197399
TI  - [Chemotherapy of primary and secondary liver tumors].
AB  - Liver is the most common site of metastatic disease. Although primary liver
      tumors are relatively rare in the Czech Republic, liver tumors represent a
      frequently encountered problem because of high incidence of colorectal and
      pancreatic cancer. Regimens of systemic chemotherapy or biologic therapy are used
      for secondary liver tumors according the primary site. It was demonstrated in
      randomized clinical studies that some of these regimens significantly prolong
      survival. Although only palliative therapy is possible for most of the patients
      with liver metastases, resection should be considered in patients with isolated
      liver involvement. Liver resection represents a curative approach and long-term
      success seems to be enhanced by neoadjuvant (preoperative) chemotherapy or
      adjuvant (postoperative) hepatic arterial chemotherapy. Hepatic arterial
      chemotherapy is also effective in the palliative treatment of unresectable liver
      metastases. Although it is still uncertain whether hepatic arterial chemotherapy
      increases survival of patients compared to systemic chemotherapy, it may be
      regarded as the best available treatment in selected patients because of better
      palliation associated with higher objective response rate and less systemic
      toxicity. Along with systemic and hepatic arterial chemotherapy, other approaches
      are being currently investigated in the treatment of primary and secondary liver
      tumors, including the use of biologic agents, agents with non-cytotoxic mechanism
      of action, or chronomodulated chemotherapy.

PMID- 12197400
TI  - [Chemoprevention in oncology].
AB  - The importance of chemoprevention is increasing nowadays because these substances
      have important biological effects, e.g. anti-inflammatory, immunomodulating and
      immunostimulating, they influence blood pressure regulation, blood sugar and
      cholesterol levels. Their anticancerogenic effects are also important as nowadays
      with regard to the type of tumourous disease it is assumed that by
      chemoprevention it is possible to restrict the development of new oncological
      diseases within a range of 30-60%. The large number of oncological patients in
      the Czech Republic (260,000 in 1997) is associated also with an adverse incidence
      (58,000 in 1997). By application of findings of chemoprevention by dietary habits
      of the population the number of patients could be markedly reduced. A realistic
      assumption for our country is a reduction by at least 12,000-16,000 of newly
      diagnosed cases per year If it were possible to apply the outlined
      recommendations on a worldwide scale every year the prevalence of oncological
      diseases would decline by 3-5 million cases.

PMID- 12197401
TI  - [Ethical aspects of treatment in patients with advanced oncologic diseases].
AB  - Ethical aspects of treatment are discussed from the aspect of medical objectives
      and the doctor-patient relationship. The authors draws attention to various
      dangers of incorrect approaches which may ensue for the patient: unnecessary and
      excessively burdening antitumourous treatment, inadequate treatment--in
      particular of pain, queer views on palliative treatment, a paternalistic approach
      of the physician with insufficient respect for the patient's wishes, inadequate
      information provided to the patient, "abuse" of patients for different
      experimental treatments etc. The author discusses in detail the double effect
      principle and draws attention to classification of means into ordinary and
      extraordinary with regard to the patient's own evaluation.

PMID- 12197402
TI  - [Changes in hemostasis in malignant diseases].
AB  - Tumourous diseases are associated with haemorrhagic as well as thrombotic
      complications. The most frequent cause of haemorrhagic states in tumourous
      diseases is thrombocytopenic haemorrhage, consumption coagulopathy and activated
      fibrinolysis. Trousseau described in 1865 a mutual association between tumourous
      diseases and venous thromboembolism. As many as 15-20% patients with venous
      thromboembolism have an undetected malignity which is a prevalence of 2-3% in the
      population. From this ensues the relative risk of a newly diagnosed malignity
      which is higher during the first year after venous thromboembolism. The
      prevalence varies between 2% and 6%. Migrating thrombophlebitiis (saltans and
      migrans) are a relatively specific sign in tumours, in particular in pancreatic
      tumours. In the pathogenesis of venous thromboembolisms in tumourous diseases in
      particular the following factors play a part: elevated coagulation parameters,
      reduced fibrinolysis, frequent immobilization, surgical operations in the case
      history, chemotherapy, hormonal therapy and central venous catheters. The authors
      present a brief review of changes of haemostasis in tumourous diseases, their
      possible diagnosis and possible pharmacological prevention and treatment of
      thromboembolisms.

PMID- 12197403
TI  - [Disorders of the cardiovascular system during treatment of oncologic diseases].
AB  - The author presents a review of cardiovascular complications of anti-tumourous
      treatment. Cardiovascular toxicity is an interdisciplinary problem which can lead
      to serious complications of oncological treatment and considerably reduce its
      benefit for the patient. Cytostatics can produce a number of undesirable side
      effects such as arrhythmias, angina pectoris, acute myocardial infarction, sudden
      death, cardiac failure. The most serious cardiotoxicity is probably chronic
      cardiac failure after anthracycline treatment. Interest in the diagnosis,
      monitoring and treatment of cardiotoxicity was aroused by new findings of cardiac
      complications after some cytostatics, high dosage chemotherapy and
      transplantation of haematopoietic cells.

PMID- 12197404
TI  - [Puncture gastrostomy in oncologic patients].
AB  - Puncture gastrostomies--percutaneous endoscopic gastrostomy and radiologically
      assisted gastrostomy--are minimally invasive methods to ensure an approach for
      the administration of enteral nutrition. These methods replaced the insertion of
      tubes during surgery (surgical gastrostomy). Percutaneous endoscopic gastrostomy
      (PEG) is inserted by means of a gastroscope, usually by the pull method,
      radiologically assisted gastrostomy (RAG) is implemented after insufflation of
      the stomach by a thin tube directly across the abdominal wall by the push method.
      In oncological patients it is preferable to administer enteral nutrition via
      puncture gastrostomy in case of obstruction of the upper portion of the digestive
      tract (oral cavity, larynx, pharynx, oesophagus), in deglutition disorders caused
      by cerebral tumours or in order to improve the nutritional status of patients
      with tumour cachexia. In the authors group in 1995-2000 a total of 53 puncture
      gastrostomies were made in 53 patients, 37 men and 16 women, mean age 62 years
      (32-94 years, incl. 38 PEG and 15 RAG. In 30 patients the reason was obstruction
      of the upper digestive tract, in 11 patients impaired swallowing associated with
      a cerebral tumour and in 12 patients the cause was tumourous cachexia. Puncture
      gastrostomies are well tolerated by the attending staff and patients, in oncology
      they can be used for administration of enteral nutrition under hospital and
      domiciary conditions.

PMID- 12197405
TI  - [Prevalence of thyroid gland disorders in pregnant women in the West Bohemia
      Region during their 2nd trimester of pregnancy in the year 2000--pilot study].
AB  - The diagnostics and the treatment of the disorders of the thyroid gland in
      pregnancy belong to the most important topics for most endocrinologists in the
      whole world. Untreated or mistreated thyroid gland disorders may influence the
      course of pregnancy and development of the foetus and child. Autoimmune
      thyroiditis, hyperthyroidism and hypothyroidism represent the most common
      thyreopaties in pregnancy and that is why the aim of the study was to establish
      their prevalence in population of pregnant women of the West Bohemia region. In
      our study we assessed serum levels of thyrotropin (TSH), free tyroxin (fT4) and
      antithyroid peroxidase antibodies (antiTPO) in 650 pregnant women. Sera were
      acquired during routine blood sampling for Down syndrome screening in the 2nd
      trimester of pregnancy. In our group we found the prevalence of 1.5% of
      hypothyroidism and 9.4% of autoimmune thyroiditis and we revealed no case of
      thyrotoxicosis, only subnormal TSH in 2.3%.

PMID- 12197406
TI  - [Immunofluorescence determination using flow cytometry of platelet surface
      antigens in peripheral blood of healthy individuals (pilot study)].
AB  - The authors present normal values of selected constitutive and activating
      platelet surface antigens expression. The results were obtained by flow cytometry
      analysis after immunofluorescent staining of the peripheral whole blood specimens
      from 25 healthy adults. Data are presented as a mean value and standard deviation
      (SD) of percentage of positive labelled platelets: constitutively expressed
      molecules CD9: 94.97% (+/- 2.95), CD31: 92.78% (+/- 2.97), CD36: 90.98% (+/-
      5.25), CD41: 95.62% (+/- 2.23), CD42a: 94.98% (+/- 2.62), CD42b: 94.13% (+/-
      2.58), activation molecules CD62P: 0.45% (+/- 0.33), CD63: 0.32% (+/- 0.22). This
      study is the first report in Czech literature.

PMID- 12197407
TI  - [Chronic pancreatitis as a risk factor for pancreatic carcinoma].
AB  - Carcinoma of the pancreas is a very serious disease as regards early diagnosis,
      effective therapy and screening of the disease. Possible risk factors of
      development of carcinoma of the pancreas include chronic pancreatitis. In the
      submitted investigation the authors evaluated 213 patients under long-term (more
      than 5 years) dispensary care with the diagnosis of chronic pancreatitis. In
      these patients they proved unequivocally carcinoma of the pancreas on the
      background of chronic pancreatitis in 11 instances, incl. 71.8% where from the
      etiological aspect chronic alcoholic pancreatitis was involved. Practically all
      patients were smokers, incl. 8 who were regular smokers of more than 10
      cigarettes per day for a number of years. Carcinoma of the pancreas is a serious
      disease, patients with long-term chronic pancreatitis are at risk (prevalence of
      carcinoma 5.1) and within the framework of dispensary care they must be
      systematically examined with regard to possible malignant growth on the
      background of chronic pancreatitis.

PMID- 12197408
TI  - [Bone changes in multiple myeloma--current etiopathogenic, diagnostic and
      therapeutic aspects].
AB  - Myelomatous bone disease affects about 90% patients with multiple myeloma and
      solitary myeloma as well. In initial stage it is manifested as osteopenia with
      osteoporosis or osteolytic foci, pathologic fractures followed by neurologic
      complications. Ethiopathogenitically a role is played by cytokine interactions
      with local chemokines produced by myeloma cells and activated stromal and
      hemopoietic cells (osteoblasts, monocytes, macrophages) resp. From the TNF-alpha
      family glycoprotein complexes are liberated (RANK-L), which support activation
      and proliferation or are inhibitory (osteoprotegerins). Similarly in the family
      TGF-beta several izotypes of antiinflammatory cytokines are known (the most
      important is TGF-beta 1 and the morphogenetic protein-2), which have a
      fibrotizing effect in bones, because the produced osteoid is insufficiently
      mineralized. The effect is a pathologic remodelation of the skeleton. In the
      diagnosis of multiple myeloma the immunological knowledge is used in the initial
      diagnosis (immunophenotypization, follow up of TNF-alpha, TGF-beta 1, IL-1, IL-6
      etc). Important are also biochemistry values of increased osteoresorption
      (changes of calcium, parathormone, excretion of collagen fission products,
      osteocalcin, the bone alkaline phosphatase). In the following part the authors
      inform about favourable results of long-term treatment with bisphosphonates
      (Bonefos, Ibandronate) in combination with anti-tumor chemotherapy in 364
      patients. During a 15 years observation period median survival of 94 months with
      a 35% probability of 10 year survival was achieved with a significant decrease of
      bone complications in 58% compared to 14% in the placebo group.

PMID- 12197409
TI  - [Monitoring cardiotoxicity of anthracyclines in children and possibilities of its
      prevention].
AB  - Chemotherapy is the basic therapeutic method in pediatric oncology. Encouraging
      results of treatment of tumours in children may be adversely influenced by late
      side effects of cytostatics. Most serious is the late cardiotoxicity of
      anthracyclines. The authors analyzed and evaluated in a retrospective study
      clinical and laboratory findings in patients treated during childhood on account
      of malignity by chemotherapy containing anthracyclines, and focused their
      attention on late toxicity and evaluation of the effect of cardioprotection of
      dexrazoxane (ICRF-187, Cardioxane). The investigation comprised 73 patients aged
      15 +/- 4.7 years who were given a cumulative dose of anthracycline (doxorubicin
      or daunorubicin) 244 +/- 13 mg/m2 and were in long-term remission of the disease.
      The mean follow up period after terminated chemotherapy was 6.7 +/- 3.4 years.
      Cardioprotection was administered to 42%, to 58% it was not administered. The
      authors did not find a significant difference in the results of anthropometric,
      haematological and biochemical examinations in the two sub-groups. A decrease of
      the left ventricular ejection fraction below 50% was diagnosed in 4 patients (5%
      of the group) whereby two developed cardiomyopathies with the clinical picture of
      heart failure and one patient died due to progressive heart failure.
      Cardiotoxicity was diagnosed only in the sub-group without cardioprotection (9.5%
      of the sub-group). In patients without cardiotoxicity in the investigated sub
      groups no significant difference was found in the left ventricular ejection
      fraction at rest or after a stress (in dynamic stress echocardiography), in the
      tolerance of a stress and circulatory indicators. A significant and relatively
      close negative relationship was found between the administered cumulative dose of
      anthracyclines and the left ventricular ejection fraction at rest (r = -0.62, p <
      0.001) and after a stress (r = -0.64, p < 0.001). CONCLUSION: The finding of a 5%
      incidence of cardiac damage of the myocardium in the whole group after a
      relatively short period after termination of chemotherapy is sufficient reason
      for long-term cardiological and in particular echocardiographic follow up of
      patients treated in childhood on account of a malignity with anthracyclines and
      for a rational approach to the administration of cardioprotection.

PMID- 12197410
TI  - [The role of infection and inflammation in the pathogenesis of atherosclerosis].
AB  - Pathogenesis of the atherosclerotic process is deemed as multifactorial. To the
      most important risk factors, besides certain family predisposition, there belongs
      hypercholesterolemia, arterial hypertension, obesity, diabetes mellitus, smoking
      and others. In the last years there are more and more data about the role of
      inflammation and infection in the whole development of atherosclerosis. The
      witness for this hypothesis is the findings of high parameters of inflammation in
      involved vessels as well as in the blood of atherosclerosis suffering persons.
      Opinions about the inflammation theory appear from the 90th. Local sterile
      inflammation in the subendotelium of the middle and big arteries has been proved
      to consist of specific immune reaction (activation of the T-lymphocytes) as well
      as nonspecific characteristic by elevated monocytes in the artery wall during the
      whole process of atherogenesis. Inflammation in the plaque can trigger and hold
      several factors engaged in the atherosclerotic process, such as oxidized LDL
      cholesterol, elevated production of various superoxides, activated macrophages,
      activated T-lymphocytes, cytokines (IL-1, IL-6, interferon gamma) and lipoprotein
      Lp (a). In this inflammation process levels of CRP (acute phase protein),
      fibrinogen and erythrocyte sedimentation are elevated as a reaction of the
      organism to nonspecific chronic infections. Because of this it is thought that
      elevated fibrinogen and erythrocyte sedimentation are markers of the
      cardiovascular risk. Some papers deal with antiinflammatory effects of statins,
      because these lower CRP levels so they also lower atherosclerotic risk through
      not only lowering of cholesterol levels. Also asprine, as an antiinflammation
      agent, changing the CRP levels, would be of benefit for patients with vascular
      disease because its antiaggregation and antiinflammatory effects. ACE inhibitors
      are also antiinflamatory through blocking of tissue production of angiotensin II
      (artery wall and atherosclerotic plaque). Enzymatic inhibitors changing
      angiotensin can also have a partial antiinflammatory effect. The infection theory
      is supported also by tracing of some microorganisms in the atherosclerotic plaque
      or in the blood, as e.g. Helicobacter pylori or Chlamydia pneumoniae; to the
      autoimmune origin is indicated the presence of the specific immunity reaction
      against heat shock proteins (HSP) or oxidized LDL. This infection theory offers
      new therapy possibilities. Therefore eradication for example by antibiotics can
      lead to stabilization of the atherosclerotic plaque with positive consequences,
      as it was discovered by many studies.

PMID- 12197411
TI  - [Ethical questions in organ transplantation].
AB  - Increased numbers of organ transplantations entailed several ethical dilemmas.
      The principles of brain death, clinical signs and a confirmation tests are well
      established and accepted by the public. The transplantation society laid down the
      principles of organ allocation, but some ethical controversies may rise in the
      situation of the significant shortage of the donors. Even if the transplantation
      law exists, the ethical problems with the opting-in or the opting-out donation
      are still open to discussion. Also the problems associated with the organ
      shortage carry several ethical controversies. The tension between increasing
      demand and steady numbers of procured organs leads to the requirement of enough
      information. The general public must be informed about the results of the
      transplantations and about all the ethical aspect of the donation in order to
      achieve general support for the transplant program.

PMID- 12197412
TI  - [Portal vein thrombosis in a patient with hyperhomocysteinemia].
AB  - The authors present the case of a 18-year-old boy examined on account of
      accidentally detected splenomegaly and suspected venous convolute in the region
      of the porta hepatis. Coeliacography revealed cavernous reconstruction of the
      portal vein due to an old thrombosis and thrombosis of the lineal vein. At the
      time of assessment of this diagnosis the patient had no apparent risk factor for
      the development of venous thromboembolic disease. With regard to the serious
      character of the finding and the patients age later detailed haemocoagulation,
      biochemical and genetic examinations were made. The only risk factor for the
      development of thrombosis which was detected was medium severe
      hyperhomocysteinaemia (46.7 mumol/l) with C677T mutation in the gene for 5,10
      methylene tetrahydrofolate reductase in the homozygous state. Although
      hyperhomocysteinaemia was identified already in the past as an important risk
      factor for the development of venous thromboembolic disease, in the available
      literature so far no case of portal vein thrombosis was described in a patient
      with hyperhomocysteinaemia as the only apparent risk factor.

PMID- 12197413
TI  - [Intravascular ultrasound guided direct stent implantation in the treatment of
      significant stenosis of the left coronary artery].
AB  - The authors present the case of a 52-year-old patient with the symptomatology of
      unstable angina pectoris where they diagnosed a major stenosis of the trunk of
      the left coronary artery as the only significant lesion in the coronary
      circulation. The patient was successfully treated by means of an intravascular
      ultrasound--guided coronary stent implanted into the trunk of the left coronary
      artery. The authors discuss the possibilities and trends of contemporary
      catheterization treatment of major coronary affections.

PMID- 12197414
TI  - Bioavailability studies on fast release formulations of indomethacin.
AB  - Indomethacin-nicotinamide solid dispersions were prepared by fusion method. Drug
      carrier interaction in the liquid and solid states were studied using phase
      solubility data and differential scanning colorimetry (DSC). DSC revealed the
      formation of an eutectic mixture of indomethacin and nicotinamide. Tablets and
      capsules, formulated from the solid dispersions showed significantly better
      dissolution and enhanced absorption rate in human volunteers, compared to
      commercial capsule of indomethacin.

PMID- 12197415
TI  - New 3-pyridinecarbonitrile derivatives and their antimicrobial properties.
AB  - 2-Alkoxy-4,6-diaryl-3-pyridinecarbonitriles 2a-f were prepared through the
      reaction of 1,3-diaryl-2-propen-1-ones 1a-c with malononitrile in the appropriate
      alcohol in the presence of sodium. The reaction was assumed to take place through
      Michael addition followed by cyclization due to the alkoxide nucleophilic attack
      at one of the nitrile groups. This assumption was substantiated by isolation of
      the open-chain Michael adduct 4, followed by independent cyclization to the
      corresponding 2-alkoxy-3-pyridinecarbonitriles 2 upon treatment with the
      appropriate alcohol in the presence of sodium. Bromination of 4a,b with bromine
      in glacial acetic acid, afforded directly the corresponding 2-bromo-3
      pyridinecarbonitriles 6a,b. The latters readily underwent nucleophilic
      substitution with different amines. The antimicrobial properties of the prepared
      compounds against Gram positive, Gram-negative, acid-fast bacteria and yeast were
      screened. Many of the prepared compounds show remarkable antimicrobial activity.

PMID- 12197416
TI  - Epoxidation of some natural furocoumarins and furochromones using gamma-ray.
AB  - Epoxidation of imperatorin (1a) with m-chloroperbenzoic acid (mcpba) under the
      irradiation of gamma-ray gave a mixture of epoxide 3a and dioxofuran 4a. Whereas,
      alloimperatorin (1b) under the same condition obtained the epoxide 3b as a sole
      product. On the other hand, it was successfully epoxidized xanthotoxin (1c) with
      mcpba under the same condition as above. In addition, visnagin (2a) was
      epoxidized to give a mixture of epoxides 5a, 6a. While, khellin (2b) gave the
      epoxide 5b, no other products were observed.

PMID- 12197417
TI  - The synthesis of some triazolylphenothiazine derivatives and their antidepressant
      and anxiolytic activities.
AB  - 10-[2-(4-Amino-5-mercapto-1,2,4-triazol-3-yl)ethyl]phenothiazine was prepared
      starting from 3-(10-phenothiaziniyl)propionic acid. This new triazole was
      employed in the synthesis of some Schiff bases and N-bridged heterocycles. All
      the newly synthesized compounds were characterized by analytical, IR, 1H-NMR and
      MASS Spectral studies. Some of the newly synthesized compounds were screened for
      their antidepressant and anxiolytic activities.

PMID- 12197418
TI  - Synthesis and antiinflammatory activity of novel 3-(2,3-dimethyl-1-phenyl-4
      pyrazolon-5-yl)-4-thiazolidones.
AB  - New 3-(2,3-dimethyl-1-phenyl-4-pyrazolon-5-yl)-4-thiazolidones were synthesized.
      The structure of substances was supported by UV- and 1H-NMR spectra. Some
      compounds were tested in vivo for their antiinflammatory activity. Were confirmed
      previous results about structure-activity relationships.

PMID- 12197419
TI  - Accelerated stability of sulphamethoxazole microcapsules coated with Eudragit RS
      100 and Eudragit RL 100.
AB  - Eudragit is being used as coating material in Microencapsulation technique for
      sustained release microcapsule formulation. In the present study, we have
      concentrated in evaluating the stability parameters of the Sulphamethoxazole
      microcapsules coated with Eudragit RS 100 and RL 100. Two sets of sample were
      studied, the first set was stored at room temperature for ten years and the
      second set is freshly prepared one. The second set of samples was subjected to
      various storage conditions for a period of six months. The samples were analyzed
      for drug content, dissolution, surface properties and physical properties. It was
      found that 70% of the core material is still intact in the ten year old sample.
      Similarly, dissolution studies of the ten year old sample of sustained release
      microcapsule showed that the drug release ranges from 4% in the first hour to 65%
      at the end of 8th hour. Whereas, the drug release from the freshly prepared
      microcapsule (keeping the manufacturing parameters same as that followed for old
      sample) ranged from 25% in the first hour to 98% at the end of 8th hour. IR
      spectra of the freshly prepared microcapsules and that of the ten year old
      microcapsules were found to be identical which shows that no interaction has
      occurred between the coating polymer and core substance even after ten years.

PMID- 12197420
TI  - Buccoadhesive tablets for insulin delivery: in-vitro and in-vivo studies.
AB  - In the present work, insulin (6 U/kg) was formulated into bioadhesive buccal
      tablets using Carbopol 934, Hydroxypropyl cellulose (HPC) or Hydroxypopylmethyl
      cellulose (HPMC) and different absorption promoters. The effect of different
      ratios of HPC or HPMC to Carbopol on the rate of water uptake was studied. The
      axial and radial detachment force as well as the duration of adhesion of tablets
      to a porcine buccal tissues were also investigated. Furthermore the hypoglycemic
      effect of some formulations containing HPMC and Carbopol in different ratios with
      different additives and enhancers was studied using diabetic male beagle dogs.
      The rate of water uptake of tablets prepared with 3:1, 1:1 or 1:3 of HPC or HPMC:
      Carbopol was directly proportion to the Carbopol content of the tablet. The
      incorporation of enhancers (10%) to tablets prepared with HPMC: Carbopol of 1:1
      ratio did not affect to a great extent the rate of tablets hydration. On the
      other hand, coating one side of the tablet with 50 mg of the impermeable cutina
      led to a significant reduction in the rate of tablets' water uptake reaching 50%
      to 75% in comparison with the uncoated tablets. Carbopol had the most influential
      effect on both mucoadhesion force and duration followed by HPMC. Tablets prepared
      with 100% HPC completely eroded within 6 hours during the measurement of the
      duration of adhesion. The incorporation of Carbopol with this polymer
      significantly improved its mucoadhesion duration reaching more than 24 hours with
      the 1:3 HPC: Carbopol. Ten percent of either sodium salicylate (NaSal) or sodium
      deoxycholate (NaDC) did not affect the duration of mucoadhesion of tablets
      prepared with 1:1 HPMC: Carbopol while 10% of Witepsol or Cacao butter and 1% of
      polyoxyethylene-9-lauryl ether (POELE) significantly reduced it. Tablets made
      using a polymer mixture of HPMC: Carbopol 934, 1:3 resulted in improved
      pharmacodynamic parameters producing a relative hypoglycemia (RH) of 6.72%.
      Furthermore, tablets made using polymer mixture of HPMC: Carbopol 934 in a ratio
      of 1:1 and containing 1% POELE resulted in 26% reduction in plasma glucose levels
      and producing 9.42% RH. Inclusion of other promoters such as 10% sodium
      deoxycholate or 10% sodium salicylate gave rise to RH values of 7.93 and 8.65%
      respectively.

PMID- 12197421
TI  - The influence of physicochemical properties of amino acid on their release from
      the Zn(II)-amino acid complexes in suspension.
AB  - The release processes of selected amino acids, for the parenteral administration,
      from the Zn(II)-Amino acid complexes in suspension were investigated in vitro.
      The Zn(II)-Amino acid complex dissociated and Zn(II) ions and amino acid were
      released. Tyrosin, possessing the highest affinity vs. the Zn(II) was released
      from the complexes in a continuous (monotonous) manner. Histidine, cysteine and
      alanine were released in a pulsating manner. The molar ratio Zn(II)-Amino acid
      determined the release rate and the manner of pulsating or continuous release of
      amino acids studied. The lower the molar ratio Zn(II)-Amino acid was, the longer
      was the amino acid release time form the complex. Molecular weight of the amino
      acids and their affinity vs. Zn(II) considerably influenced the continuous
      release rate from the complex. The higher the molecular weight of an amino acid,
      the lower was its extent of the release from the complex. The amino acids
      possessing higher affinity vs. Zn(II) were more slowly released too. The slowest
      release was observed for tyrosine which possessed the aromatic chemical
      structure, and the quickest release was in the case of the aliphatic amino acid-
      alanine. The obtained complexes were characterised by the moderated release of
      the amino acids in vitro.

PMID- 12197423
TI  - Prescribing patterns analysis in Bulgaria.
AB  - This study was developed to assess the prescribing patterns in the reimbursable
      and non-reimbursable prescriptions during 1996-2000 and their relevance to
      morbidity patterns in Bulgaria. It was manually collected 2266 reimbursable and
      2330 non-reimbursable prescriptions with 4132 and 4291 prescribed drugs,
      respectively. The results shows that the leading causes for morbidity during 1995
      99 were respiratory tract diseases with 40% relative share, followed by nervous
      system diseases with 12% share, cardiovascular diseases 10% share, digestive
      tract diseases, genito-urinary, skin and subcutaneous tissue diseases. All
      mentioned groups of diseases together with injuries and poisoning perform 70% of
      the total morbidity of the population. The prevailing causes for the mortality of
      the population were found to be cardiovascular, respiratory tract diseases,
      injuries and poisoning. The analysis of the collected prescriptions evaluated as
      mot often prescribed cardiovascular drugs (35%), drugs acting on digestive system
      (18%), nervous system (12%), respiratory system (11%) and anti-infective drugs
      (10%). In spite of the relevance among the prescribing and morbidity a lot of
      other factors are considered to be important as reimbursement system, pricing,
      and legislation.

PMID- 12197422
TI  - Study of the stability of tablets containing 10 mg of policosanol as active
      principle.
AB  - The stability studies of tablets containing 10 mg of policosanol, a new
      cholesterol lowering drug, were conducted to predict an expiration date and to
      search the appearance of putative degradation products. All quality specification
      parameters such as colour, moisture content, hardness, disintegration,
      policosanol content and microbiological limits of the tablets were done. The
      effect of drastic treatments such as acid and basic hydrolysis, oxidative and
      photolytic degradation as well as thermolysis on such parameters was studied. In
      addition; studies under drastic conditions of storage (40 degrees C and 75% R.H.)
      and under ambient conditions of storage for climatic zones II and IV were
      performed. These studies demonstrate that these tablets are a stable
      pharmaceutical formulation, without significant changes on their quality criteria
      at the stressed conditions studied. The chromatographic profile of the samples
      after 9 months of thermal degradation shows chromatographic peaks that
      corresponds to the octacosanoyl, triacontanoyl and hexacosanoyl esters of
      palmitate and stearate, being the only degradation products observed on these
      studies.

PMID- 12197424
TI  - Antimicrobial activity of Verbascum macrurum Ten. (Scrophulariaceae).
AB  - The Author presents the results regarding the antibacterial action of extracts of
      Verbascum macrurum Ten.. The leaves of this species, gathered on the slopes of
      Mt. Matese, were ground and four extracts were made as follows: with
      dicholoromethane, ethonol and water (70:30 v/v), water and methanol. The
      antibacterial activity of each of the samples was tested and it is demonstrated
      that the extract with the ethanol/water was the most activity one.

PMID- 12197425
TI  - Evaluation of the sedative properties of the ethanolic root extract of
      Cissampelos mucronata.
AB  - The ethanolic root extract of Cissampelos mucronata was investigated for sedative
      activity. Phytochemical analysis indicated the presence of alkaloids:
      sterols/triterpenes, tannins, carbohydrates, glycosides, and flavonoids. Acute
      lethality test gave an LD50 of 282.84 mg/kg. The study of the effect of the
      extract on the behavioural pattern of mice showed changes indicative of central
      nervous system depression. The results further revealed that the extract
      progressively reduced ephedrine-induced spontaneous motor activity in rats, and
      prolonged pentobarbitone-sleeping time in mice. Pre-treatment of mice with the
      extract also protected 40% of the animals against pentylenetetrazole-induced
      convulsions. The mechanism of action is not precisely known but may probably be
      attributed to central nervous system depressant action.

PMID- 12197426
TI  - Antituberculosis agents. III. In vitro evaluation of antimycobacterial activity
      and cytotoxicity of some N-piperazinyl quinolone derivatives.
AB  - A series of N-[2-oxo-2-(4-substitutedphenyl)ethyl]piperazinyl quinolones(1a-e,2a
      e and 3a-c) and N-[2-hydroxyimino-2-(4-substitutedphenyl)ethyl]piperazinyl
      quinolones(1f-j,2f-j and 3d-f) were evaluated for antituberculosis activity
      against Mycobacterium tuberculosis H37R, using the BACTEC 460 radiometric system
      and BACTEC 12B medium. Active compounds were also screened by serial dilution to
      assess toxicity to a VERO cell line. Nine compounds were efficient
      antimycobacterial agents showing MIC values ranging from 0.78 to 6.25
      micrograms/ml. Generally, ciprofloxacin derivatives were more active than
      norfloxacin and enoxacin derivatives and the oxime analogues were less active
      than corresponding ketones. The most selective and less toxic compound 1a was
      tested for efficacy in vitro in TB-infected macrophage model (EC90 = 3.68
      micrograms/ml, EC99 = 9.18 micrograms/ml).

PMID- 12197427
TI  - The simultaneous combination of implants and tram flaps for an aesthetically
      pleasing breast.
AB  - In Taiwan, there have quite often been incidences when patients have had more
      abundant abdominal tissue to make a TRAM flap with a volume larger than the
      contralateral breast. In these situations, we usually recommend performing
      contralateral augmentation mammoplasty with a saline implant while undergoing
      TRAM flap reconstruction. From February 1997 to Mar 2001, 250 breast cancer
      patients underwent immediate pedicled TRAM flap reconstructions at Kaohsiung
      Medical University Hospital. Of these, 10 cases not only had TRAM flaps, but also
      simultaneous insertion of a prosthesis into the contralateral/bilateral breast to
      form a more pleasing breast mound. These were all saline implants. Each patient
      was young (aged 31-51 years) and had small to medium sized breasts. During the
      procedure, the implants were placed in a submuscular pocket formed by the
      pectoralis major muscle. There were no significant complications or failures. All
      breasts have remained soft and natural-looking during the follow-up period. Nine
      of 10 patients appreciated this procedure, and 8 of them would agree to convince
      other patients of the benefits of this operation. Using pedicled TRAM flaps and
      saline breast implants can achieve immediate breast reconstruction without the
      need for prolonged tissue expansion or an obvious back scar. Aesthetic results
      are excellent and the immediate use of an implant does not appear to pose a risk
      to the success of the pedicle transfer. It is a good alternative for breast
      cancer patients with previous hypoplasia of the breasts to achieve simultaneous
      therapeutic and cosmetic results.

PMID- 12197428
TI  - Bacteriology and antimicrobial susceptibility in biliary tract disease: an audit
      of 10-year's experience.
AB  - Cholelithiasis, choledocholithiasis and hepatolithiasis are common biliary tract
      diseases. These diseases may cause severe infection and/or sepsis. In addition to
      surgical treatments, prompt administration of appropriate antibiotic is important
      to control the biliary tract infection. The purpose of this study is to
      illustrate the bacteriology in biliary tract disease and provide information for
      antibiotic choices. From Jan 1991 to Aug 2000, 1394 patients including
      gallbladder (GB) stones, common bile duct (CBD) stones, intrahepatic duct (IHD)
      stones, GB polyps and biliary malignancy were subjects for this retrospective
      study. The overall positive rate of bile culture is 36% in this study while it
      was 25%, 66%, 67% and 9% for GB stones, CBD stones, IHD stones and biliary
      malignancy, respectively. A significantly higher (p = 0.001) positive culture
      rate was found for GB stones with acute cholecystits (47%) compared with that
      without inflammation (17%). Similarly, the culture rate for hepatolithiasis with
      acute cholangitis was higher than that without cholangitis (75% vs 51%, p =
      0.011). Long-term external biliary drainage in biliary malignancy increased the
      risk of bacterial culture rate. For gallstone diseases, the most common organisms
      cultured were Gram negative bacteria (74%), in which Escherichia coli (36%) and
      Klebsiella (15%) were most commonly found, followed by Gram positive (15%)
      bacteria such as Enterococcus (6%), Staphylcoccus (3%), Streptococcus (2%).
      Bacteroides (5%) and Clostridium (3%) were occasionally found anaerobes (9%).
      Polymicrobial infection was encountered in 19%, 31% and 29% for patients with GB
      stones, CBD stones and IHD stones, respectively; frequency of mixed aerobic and
      anaerobic infection was 7%, 12% and 9%. In the current study, ampicillin in
      combination with sulbactam and aminoglycoside is still a suggestive empirical
      therapy. Antibiotic treatment should be adjusted based on later bacteriological
      cultures and clinical condition.

PMID- 12197429
TI  - Effect and correlation of serum total IgE, eosinophil granule cationic proteins
      and sensitized allergens in atopic dermatitis patients with or without rhinitis.
AB  - To understand the relevance of serological parameters and eliciting allergens in
      the patients with atopic dermatitis (AD) and patients with atopic dermatitis in
      combination with rhinitis (ADR), we compared the serum total IgE, major basic
      protein (MBP) and eosinophil cationic protein (ECP) levels and identified the
      sensitized allergens in these two groups. The serum levels of total IgE, MBP and
      ECP were not significantly different in these two groups. Patients with ADR had a
      higher positive rate of aeroallergens including housedust, mite (D.F), mite (D.P)
      and cockroach than patients with AD. However, a high positive rate of seafood
      allergens (include crab, shellfish and shrimp) was observed in patients with AD.
      The serum IgE level correlated well with serum MBP level (r = 0.603, P = 0. 019)
      in patients with ADR. There was a strong correlation between serum MBP and ECP
      level (r = 0.773, P = 0.005) in patients with AD and in patients with ADR (r =
      0.721, P = 0.008). We also found that numbers of sensitized allergens correlated
      well with total IgE in patients with AD (r = 0.760, P = 0.001) and in patients
      with ADR (r = 0.487, P = 0.004). These results suggested that the aeroallergens
      are the most important allergens causing and aggravating atopic diseases in
      Taiwan. Seafood may play an important role in the pathogenesis of AD. We suggest
      the measurement of serum total IgE combined with Multiple Allergens Simultaneous
      Test-Chemiluminescent Assays(AST-CLA) test could be helpful in the diagnosis of
      atopic diseases.

PMID- 12197430
TI  - Cold effect on qt dispersion in healthy subjects.
AB  - Thirty-one healthy subjects, aged 35 +/- 6 (21 to 48) years, were included in the
      study to evaluate the effect of ice water immersion on QT dispersion. There was
      no difference in the age between females (n = 11) and males (n = 20). Baseline,
      stress (at the end of ice water immersion, 4 degrees C, for 3 minutes) and
      recovery 12-lead electrocardiograms (ECGs) were recorded on each subject. During
      the test, a significant variability developed in both the QT dispersion (52 +/-
      17, 68 +/- 25 and 59 +/- 21 ms; p = 0.015) and the corrected QT dispersion (56 +/
      17, 76 +/- 27 and 64 +/- 23 ms; p = 0.005), but not in the heart rate (74 +/-
      11, 76 +/- 9, and 74 +/- 9 bpm, respectively; p = 0.447). There was no inter-sex
      difference in the baseline heart rate or QT dispersion, or in their response to
      ice water immersion. Age significantly correlated with the variation of QT
      dispersion to ice water immersion (r = 0.380, p = 0.035). With 37 years of age as
      a separation point, the variation of QT dispersion to ice water immersion was
      more obvious in the older group (28 +/- 22 vs. 10 +/- 19 ms, p = 0.023). In
      conclusion, cold may increase QT dispersion in healthy subjects, with a more
      obvious effect in the older ones.

PMID- 12197431
TI  - Evaluation of muscle strength in patients with spinal muscular atrophy.
AB  - The first aim of this study was to evaluate the muscular strength in order to
      document the strength scores for patients with spinal muscular atrophy (SMA). The
      second aim was to analyze the differences in average strength score among the
      musculatures at various body parts. Twenty-five patients with type II SMA (mean
      age of 13.7 +/- 7.0 years) and 15 patients with type III SMA (mean age of 13.7 +/
      8.2 years) were enrolled to undergo a muscle strength evaluation using the
      method of manual muscle testing. For each patient, the strength of 71 muscle
      groups were graded using a numerical ordinal scale to obtain individual muscle
      group scores, average scores of the arms, legs, the musculatures around the
      limbs' joints, the arm flexors and extensors, and leg flexors and extensors. The
      data were analyzed using a statistic model of multivariate analysis of variance
      and paired t-test. All data were administrated respectively for type II and type
      III SMA. The results showed that in both types of patients, the trunk muscles and
      the musculatures around the hips possessed lower strength scores, whereas elbow
      flexors, wrist flexors and extensors, finger flexors, and diaphragms exhibited
      relatively higher strength scores. In type II SMA the average scores of the
      musculatures of the left side arms was lower than those of the right side at the
      joints of scapulas, elbows and wrists. Our data also showed the arm flexor scores
      were higher than the arm extensor scores in both types, whereas significant
      higher score of the leg flexor in comparison to the leg extensor was only found
      in the patients with type II SMA. The profiles of muscle strength and strength
      differences over various body parts in the patients with type II SMA as well as
      the type III SMA were obtained from this study.

PMID- 12197432
TI  - Mycotic aneurysm of thoracic aorta with aortoesophageal fistula mimicking the
      esophageal tumor with bleeding--a case report.
AB  - An aortoesophageal fistula is a rare but fatal disease, most commonly associated
      with thoracic aortic aneurysm. Early diagnosis and emergency surgical
      intervention are mandatory for survival. We reported a case of mycotic aneurysm
      of thoracic aorta with aortoesophageal fistula, presenting with intermittent
      hematemesis, tarry stool and sepsis. Initially, misdiagnosis of esophageal
      submucosal tumor with bleeding was made clinically and endoscopically. With
      contrast-enhanced spiral computed tomography (CT) scan the diagnosis was
      confirmed. The pathogenesis, clinical presentation, endoscopic feature and
      imaging findings were reviewed.

PMID- 12197433
TI  - Glomangioma at the cervical spine as an extradural dumbbell-shaped tumor--a case
      report.
AB  - A case of glomangioma located at an unusual site, the extradural space of the
      cervical spine, is presented. To our knowledge, this is the first case that has
      been identified at this location. Radiographic features of computed tomography
      (CT) and magnetic resonance (MR) image were collected as a dumbbell-shaped tumor
      at epidural space of the cervical spine. These features correspond with the
      histological findings.

PMID- 12197435
TI  - Suggestions for more effective rail crossing lights.

PMID- 12197434
TI  - Radiation retinopathy--a case report.
AB  - Radiation retinopathy is one of ocular complications in radiation therapy for
      many diseases. It is a slowly progressive, delayed-onset disease of retinal blood
      vessels. A 49 year-old Chinese female suffered from blurred vision for 2 years
      progressively. The best corrected visual acuity was 0.02 and 0.06 in her right
      and left eyes respectively. Ophthalmic fundus examination showed hard exudate,
      retinal hemorrhage, and macular edema in both her eyes. Tracing back her history,
      she had nasopharyngeal carcinoma and received irradiation treatment 11 years ago.
      She denied diabetic mellitus or other systemic disease. After laser
      photocoagulation treatment, she had better vision with the best corrected visual
      acuity 0.2 and 0.3 in her right and left eyes respectively 1 year later.

PMID- 12197436
TI  - Ergo, the Roller Mouse.

PMID- 12197437
TI  - The fast track to fire protection.

PMID- 12197438
TI  - Automated fire & safety inspections ... in your pocket.

PMID- 12197439
TI  - Fire precautions for welding.

PMID- 12197440
TI  - Current issues in confined spaces.

PMID- 12197441
TI  - Detection of drug abuse by health professionals.

PMID- 12197442
TI  - Atmospheric hazards in construction work.

PMID- 12197443
TI  - Re: OH&S article "stop the sacrifices" from June 2002 issue.

PMID- 12197444
TI  - Mirror, mirror on the wall, which enantiomer is fairest of them all?
AB  - Numerous psychotropic drugs exist as a mixture of 2 mirror-image stereoisomers of
      each other, each called an enantiomer and the mixture called a racemate. Often
      the drug can be improved when only 1 of the enantiomers is administered.

PMID- 12197446
TI  - Anger and aggression in psychiatric outpatients.
AB  - BACKGROUND: This study sought to evaluate the degree of anger and aggression
      experienced by psychiatric outpatients and to determine whether anger is as
      prominent an emotional state in these patients as are depression and anxiety. We
      also sought to determine which Axis I and Axis II disorders were associated with
      increased rates of subjective anger and aggressive behavior. METHOD: 1300
      individuals presenting to a psychiatric outpatient practice underwent
      semistructured interviews to evaluate current DSM-IV Axis I (N = 1300) and Axis
      II disorders (N = 687). Levels of subjective anger and aggression during the
      preceding week were assessed in each patient, and the odds ratios were calculated
      for each disorder. A multiple regression analysis was performed to determine
      which psychiatric disorders independently contributed to the presence of
      subjective anger and aggressive behavior. RESULTS: Approximately one half of our
      sample reported currently experiencing moderate-to-severe levels of subjective
      anger, and about one quarter had demonstrated aggressive behavior in the
      preceding week. This level of anger was found to be comparable to the levels of
      depressed mood and psychic anxiety reported by our sample. Major depressive
      disorder, bipolar I disorder, intermittent explosive disorder, and cluster B
      personality disorders independently contributed to the presence of both anger and
      aggression. CONCLUSION: Anger and aggression are prominent in psychiatric
      outpatients to a degree that may rival that of depression and anxiety; it is
      therefore important that clinicians routinely screen for these symptoms.

PMID- 12197445
TI  - Differential prescription of maintenance antipsychotics to African American and
      white patients with new-onset bipolar disorder.
AB  - BACKGROUND: Antipsychotic medications are commonly prescribed as maintenance
      pharmacotherapy for patients with bipolar disorder. However, double-blind,
      placebo-controlled studies have yet to demonstrate a significant prophylactic
      effect of maintenance antipsychotic use in bipolar disorder, and long-term use of
      antipsychotics may place the patient at risk for neuroleptic-induced tardive
      dyskinesia. African American patients may be at increased risk because excess
      antipsychotic prescription appears to be common in this population, although this
      issue has not been longitudinally studied in bipolar disorder. METHOD: Fifty
      eight patients meeting DSM-IV criteria for bipolar I disorder, with manic or
      mixed episode, were recruited at the time they were admitted for a first
      psychiatric hospitalization and then received longitudinal follow-up for up to 2
      years. Comparisons were made between African American (N = 24) and white (N = 34)
      patients in medications prescribed and medication compliance after controlling
      for differences in clinical course. RESULTS: The African American and white
      patient groups were similar demographically. After controlling for differences in
      clinical course, African Americans, compared with white patients, (1) received
      antipsychotics for a significantly greater percentage of follow-up time (F = 7.9,
      df = 1.52; p < .007), (2) were more likely to receive antipsychotics during
      periods without psychotic symptoms, and (3) were significantly more likely to
      receive conventional antipsychotics (chi 2 = 4.0, df = 1, p < .05). African
      Americans also demonstrated poorer treatment adherence, although that finding did
      not explain the differences in antipsychotic prescription. CONCLUSION: Even when
      demographically similar to white patients, African Americans with bipolar
      disorder may be more likely to receive maintenance antipsychotic treatment. The
      specific reasons for this finding are not clear, suggesting that studies are
      warranted that examine clinicians' rationale for differentially prescribing
      antipsychotics for African American and white patients during the early course of
      bipolar disorder.

PMID- 12197447
TI  - Sleep Dynamic Therapy for Cerro Grande Fire evacuees with posttraumatic stress
      symptoms: a preliminary report.
AB  - BACKGROUND: Sleep disturbance is common among disaster survivors with
      posttraumatic stress symptoms but is rarely addressed as a primary therapeutic
      target. Sleep Dynamic Therapy (SDT), an integrated program of primarily evidence
      based, nonpharmacologic sleep medicine therapies coupled with standard clinical
      sleep medicine instructions, was administered to a large group of fire evacuees
      to treat posttraumatic insomnia and nightmares and determine effects on
      posttraumatic stress severity. METHOD: The trial was an uncontrolled, prospective
      pilot study of SDT for 66 adult men and women, 10 months after exposure to the
      Cerro Grande Fire. SDT was provided to the entire group in 6, weekly, 2-hour
      sessions. Primary and secondary outcomes included validated scales for insomnia,
      nightmares, posttraumatic stress, anxiety, and depression, assessed at 2
      pretreatment baselines on average 8 weeks apart, weekly during treatment,
      posttreatment, and 12-week follow-up. RESULTS: Sixty-nine participants completed
      both pretreatment assessment, demonstrating small improvement in symptoms prior
      to starting SDT. Treatment and posttreatment assessments were completed by 66
      participants, and 12-week follow-up was completed by 59 participants. From
      immediate pretreatment (second baseline) to posttreatment, all primary and
      secondary scales decreased significantly (all p values < .0001) with consistent
      medium-sized effects (Cohen's d = 0.29 to 1.09), and improvements were maintained
      at follow-up. Posttraumatic stress disorder subscales demonstrated similar
      changes: intrusion (d = 0.56), avoidance (d = 0.45), and arousal (d = 0.69).
      Fifty-three patients improved, 10 worsened, and 3 reported no change in
      posttraumatic stress. CONCLUSION: In an uncontrolled pilot study, chronic sleep
      symptoms in fire disaster evacuees were treated with SDT, which was associated
      with substantive and stable improvements in sleep disturbance, posttraumatic
      stress, anxiety, and depression 12 weeks after initiating treatment.

PMID- 12197448
TI  - Combining antidepressants for treatment-resistant depression: a review.
AB  - OBJECTIVE: Many patients with depression remain poorly responsive to
      antidepressant monotherapy. One approach for managing treatment-resistant
      depression is to combine antidepressants and to capitalize on multiple
      therapeutic mechanisms of action. This review critically evaluates the evidence
      for efficacy of combining antidepressants. METHOD: A MEDLINE search of the last
      15 years (up to June 2001), supplemented by a review of bibliographies, was
      conducted to identify relevant studies. Criteria used to select studies included
      (1) published studies with original data in peer-reviewed journals, (2) diagnosis
      of depression with partial or no response to standard treatments, (3) any
      combination of 2 antidepressants with both agents used to enhance antidepressant
      response, (4) outcome measurement of clinical response, and (5) sample size of 4
      or more subjects. RESULTS: Twenty-seven studies (total N = 667) met the inclusion
      criteria, including 5 randomized controlled trials and 22 open-label trials. In
      the 24 studies (total N = 601) reporting response rates, the overall mean
      response rate was 62.2%. Methodological limitations included variability in
      definitions of treatment-resistant depression and response to treatment, dosing
      of medications, and reporting of adverse events. CONCLUSION: There is limited
      evidence, mostly in uncontrolled studies, supporting the efficacy of combination
      antidepressant treatment. Further randomized controlled trials with larger sample
      sizes are required to demonstrate the efficacy of a combination antidepressant
      strategy for patients with treatment-resistant depression.

PMID- 12197449
TI  - Selecting methodologies for the evaluation of differences in time to response
      between antidepressants.
AB  - BACKGROUND: The delay in the therapeutic effect of antidepressants is a
      considerable impediment to their successful clinical use, and attention has
      recently been focused on antidepressant drugs that may have a faster onset of
      action. DATA SYNTHESIS: Several methodologies exist for evaluating differences in
      time to response between antidepressants including the identification of the
      timepoint at which statistically or clinically significant differences between
      treatment groups emerge, pattern analysis, and survival analytical approaches.
      All have conceptual as well as practical advantages and disadvantages.
      CONCLUSION: The survival analytical approach is generally considered to be the
      most rigorous and sensitive in detecting differences in the speed of response of
      antidepressants, but the other methodologies provide useful information.

PMID- 12197450
TI  - Quetiapine addition to serotonin reuptake inhibitor treatment in patients with
      treatment-refractory obsessive-compulsive disorder: an open-label study.
AB  - OBJECTIVE: Although patients with obsessive-compulsive disorder (OCD) benefit
      from treatment with serotonin reuptake inhibitors (SRIs), it is estimated that
      40% to 60% of the patients remain unimproved. The objective of this study was to
      examine whether addition of the atypical antipsychotic quetiapine to SRIs is
      useful for patients with OCD who do not respond to SRI monotherapy. METHOD: Ten
      patients with OCD (DSM-IV criteria) who had not responded to at least 3 previous
      treatments with an SRI at maximum dose and duration were assigned to receive
      quetiapine in addition to an SRI for 8 weeks. Treatment response was assessed
      using the Yale-Brown Obessive-Compulsive Scale (YBOCS). RESULTS: Seven of 10
      patients responded to the quetiapine addition. The mean +/- SD baseline YBOCS
      score of 31.4 +/- 7.8 dropped to a mean of 20.8 +/- 8.4 at endpoint with a mean
      reduction of 35.4%. CONCLUSION: This is the first study to show that treatment
      refractory OCD patients may benefit from addition of quetiapine to ongoing SRI
      therapy.

PMID- 12197451
TI  - Citalopram treatment of compulsive shopping: an open-label study.
AB  - BACKGROUND: Compulsive shopping, a DSM-IV impulse-control disorder not otherwise
      specified, is characterized by preoccupation with shopping and inability to
      resist buying unneeded items, with resulting marked distress, social or
      occupational impairment, and financial and/or familial problems. Because an open
      label trial suggested that fluovaxamine, a selective serotonin reuptake inhibitor
      (SSRI), is effective for this disorder, we tested the effectiveness of the SSRI
      citalopram. METHOD: We enrolled adults meeting formal diagnostic criteria (as
      defined by McElroy and colleagues) in a 12-week open-label trial. We excluded
      subjects with obsessive-compulsive disorder, bipolar disorder, substance abuse or
      dependence, or psychotic disorders. Citalopram treatment was begun at 20 mg/day
      and increased every 2 weeks by 20 mg/day, absent marked response and limiting
      side effects, to 60 mg/day. At endpoint, all subjects were asked to give written
      informed consent for follow-up telephone interviews at 3-month intervals for 12
      months. RESULTS: We enrolled 24 subjects, 22 women and 2 men, whose mean +/- SD
      age was 43.7 +/- 8.1 years; most had been shopping compulsively for 2 decades or
      more. Citalopram (mean +/- SD endpoint dose = 35.4 +/- 21.4 mg/day) produced
      rapid, marked, sustained improvements on both the Yale-Brown Obsessive Compulsive
      Scale-Shopping Version and the Clinical Global Impressions-Improvement (CGI-I)
      scale in subjects with and without comorbid conditions. Seventeen subjects (71%)
      were responders, achieving ratings of much or very much improved on the CGI-I,
      including 2 of the 3 subjects who discontinued for adverse events (sedation or
      agitation). During a 6-month follow-up period, those continuing citalopram
      therapy were less likely to relapse than those discontinuing the medication.
      CONCLUSION: Citalopram appears to be a safe and effective treatment for
      compulsive shopping. Acute and long-term, double-blind, placebo-controlled trials
      of citalopram and other SSRIs for the treatment of this disorder are indicated.

PMID- 12197453
TI  - Identification of a claims data "signature" and economic consequences for
      treatment-resistant depression.
AB  - BACKGROUND: Major depressive disorder (MDD) is a debilitating condition with
      significant economic consequences. Conservative estimates indicate that between
      10% and 20% of all individuals with MDD are treatment resistant. The objectives
      for this study were (1) to use current treatment strategies identified in the
      literature to evaluate the validity of studying treatment-resistant depression
      (TRD) using claims data and (2) to estimate cost differences between TRD-likely
      and TRD-unlikely patients identified by use of treatment patterns. METHOD: The
      data source consisted of medical, pharmaceutical, and disability claims from a
      Fortune 100 manufacturer for 1996 through 1998 (N = 125,242 continuously enrolled
      beneficiaries between the ages of 18 and 64 years). The sample included
      individuals with medical or disability claims for MDD (NMDD = 4186). A treatment
      pattern algorithm was applied to classify adult MDD patients into TRD-likely
      (NTRD = 487) and TRD-unlikely groups. Resource utilization and costs were
      compared among TRD-likely and TRD-unlikely patients and a random sample of
      average beneficiaries (i.e., 10% of all beneficiaries) for 1998. RESULTS:
      Consistent with the epidemiologic literature, the algorithm classified 12% of the
      MDD sample as TRD-likely. Mean annual costs were $10,954 for TRD-likely patients,
      $5025 for TRD-unlikely patients, and $3006 for average beneficiaries. TRD-likely
      patients used almost twice as many medical services as did TRD-unlikely patients
      and incurred significantly greater indirect costs (p < .0001). CONCLUSION: It is
      feasible to use an administrative dataset to develop a claim-based treatment
      algorithm to identify TRD-likely patients. Resource utilization by TRD-likely
      patients was substantial, not only for direct treatment of depression but also
      for treatment of comorbid medical conditions. Additionally, TRD imposed on
      employers substantial indirect costs resulting from high rates of depression
      associated disability.

PMID- 12197452
TI  - Sexual function and satisfaction in the treatment of chronic major depression
      with nefazodone, psychotherapy, and their combination.
AB  - BACKGROUND: Changes in sexual interest/satisfaction and function are frequently
      associated with major depression and the use of some antidepressant treatments.
      This study compares the effects of antidepressant medication, psychotherapy, and
      combined treatment on sexual interest/satisfaction and function in patients with
      chronic major depression. METHOD: Outpatients with chronic forms of DSM-IV major
      depressive disorder (N = 681) were randomly assigned to 12 weeks of nefazodone,
      Cognitive Behavioral Analysis System of Psychotherapy (CBASP), or combined
      nefazodone/CBASP. The Modified Rush Sexual Inventory was used to assess sexual
      functioning, and the 24-item Hamilton Rating Scale for Depression was used to
      assess depressive symptoms. RESULTS: At baseline, 65% of men and 48% of women
      reported some sexual dysfunction. Statistically significant linear improvement in
      sexual interest/satisfaction was noted across all 3 treatment groups (p < .001).
      Additionally, significant improvement in sexual function was observed across all
      3 treatment groups on a composite measure of female sexual function (p < .001).
      Controlling for depressive symptoms and gender, combined treatment produced
      greater improvement in total sexual interest/satisfaction than CBASP alone (p =
      .007), but was not significantly different from nefazodone alone. Improvement in
      depressive symptoms was associated with improved sexual interest/satisfaction for
      men and women and, for men, improved sexual functioning. CONCLUSION: Chronic
      depression is associated with high rates of sexual dysfunction. Treatment with
      nefazodone, CBASP, and combined treatment improved sexual interest/satisfaction,
      with greatest improvement observed with combined treatment.

PMID- 12197454
TI  - Antidepressant medication management and Health Plan Employer Data Information
      Set (HEDIS) criteria: reasons for nonadherence.
AB  - BACKGROUND: While nationwide data have found that many patients do not meet the
      National Committee for Quality Assurance uniform standards for successful
      antidepressant treatment, reasons for this failure are not well understood. We
      examined the reasons for this failure through a systematic chart review. METHOD:
      A chart review was conducted on a random sample of 249 health maintenance
      organization patients who failed 1 or more of the 3 Health Plan Employer Data
      Information Set criteria (i.e., 3 follow-up visits or adequate duration of acute
      or continuation phase treatment). RESULTS: The most common reason for visits
      failure (N = 192) was that the patient restarted a previously prescribed
      successful antidepressant (N = 30, 16%). In 23 patients (12%), the patient had a
      visit with the prescribing provider, but mental health was not coded or
      documented in the case notes. Twenty-one percent (N = 40) were misclassified as
      not having 3 visits. The most common reasons for misclassification were mental
      health was discussed but not coded (N = 16, 8%) and wrong start dates due to use
      of medication samples (N = 10, 5%). Patient nonadherence was the most common
      reason for failure to meet adequate acute (N = 109) and continuation (N = 99)
      phase duration of treatment (13% and 24%, respectively); only 9% stopped taking
      medication in the acute phase due to side effects. Twenty-five percent of
      patients had told their doctor they were taking their medication while the
      pharmacy database found they were not. CONCLUSION: A large discrepancy between
      patients' actual and reported compliance was found and may in part account for
      physicians' inability to detect and thus address this issue. Patients' restarting
      a previous medication is common and warrants discussion regarding differential
      need for visit frequency.

PMID- 12197455
TI  - An open pilot study combining risperidone and a selective serotonin reuptake
      inhibitor as initial antidepressant therapy.
AB  - BACKGROUND: Atypical antipsychotics such as risperidone or olanzapine have been
      reported to be effective when added to a selective serotonin reuptake inhibitor
      (SSRI) in cases of depression in which treatment with an SSRI alone is not
      effective. It is possible that the combination of an SSRI and an atypical
      antipsychotic may be efficacious as an initial treatment for major depression.
      METHOD: Thirty-six subjects who fulfilled DSM-IV diagnostic criteria for major
      depressive disorder were given fluvoxamin, 50 or 75 mg/day, with risperidone, 0.5
      or 1 mg/day, at the start of treatment. The dose of fluvoxamine was increased to
      100 or 150 mg/day on the fourth day of the treatment and maintained thereafter.
      Hamilton Rating Scale for Depression (HAM-D) scores were obtained at base-line
      and every week for 6 weeks. Remission and response were defined, respectively, as
      > or = 75% and 50%-74% reduction from baseline in HAM-D score. RESULTS: Of 30
      subjects who completed the 6-week study, 23 (76%) achieved remission, 5 (17%)
      achieved response, and 2 (7%) were nonresponsive. Of the 6 patients who did not
      complete the study, 3 showed remission, 1 showed response, and 2 showed minimal
      or no response by the time of dropout. The reported adverse effects were mild,
      and none of the 36 subjects enrolled in the study manifested or reported
      extrapyramidal symptoms, nausea, or vomiting. CONCLUSION: The results suggest
      that the combination of risperidone and fluvoxamine from the beginning of
      antidepressant therapy enhances the therapeutic response rate in depression.

PMID- 12197456
TI  - Lamotrigine as an augmentation agent in treatment-resistant depression.
AB  - BACKGROUND: The anticonvulsant lamotrigine has been reported to be efficacious
      and well tolerated as monotherapy in the treatment of bipolar patients as well as
      in treatment-refractory bipolar disorder. However, there is a paucity of research
      on the use of lamotrigine as an augmentation agent in treatment-refractory
      unipolar major depressive disorder. METHOD: This study was a retrospective chart
      review on the efficacy of lamotrigine augmentation in 37 individuals diagnosed
      with chronic or recurrent major depressive disorder (DSM-IV) who had failed to
      respond adequately to at least 2 previous trials of antidepressants. Thirty-one
      patients who were on lamotrigine treatment for at least 6 weeks (6 discontinued
      prematurely due to adverse events) took a mean dose of 112.90 mg/day for a mean
      of 41.80 weeks. The primary efficacy parameter for this study was the Clinical
      Global Impressions scale, which was retrospectively applied. In addition, these
      data were supplemented by an analysis of prospectively rated Global Assessment of
      Functioning scores. RESULTS: On the basis of intent-to-treat analysis, response
      rates were as follows: 40.5% (15/37) much improved or very much improved, 21.6%
      (8/37) mildly improved, and 37.8% (14/37) unchanged. The percentage of patients
      who were rated much or very much improved and completed 6 weeks on the drug was
      48.4% (15/31). No differences were found in the doses of lamotrigine given to
      responders and nonresponders. CONCLUSION: Analyses revealed that lamotrigine
      treatment was most effective for patients who had been depressed for shorter
      periods of time and had failed fewer previous trials of antidepressants. Data
      also suggested a trend toward increased response for patients with comorbid
      anxiety disorders and/or chronic pain syndromes.

PMID- 12197457
TI  - Oxcarbazepine-induced syndrome of inappropriate secretion of antidiuretic
      hormone.

PMID- 12197458
TI  - The role of micronutrients as possible mood-stabilizing agents.

PMID- 12197459
TI  - Gabapentin and PTSD.

PMID- 12197460
TI  - Foreword: phase II of the genetics revolution: sophisticated issues for home and
      abroad.

PMID- 12197461
TI  - Protecting the endangered human: toward an international treaty prohibiting
      cloning and inheritable alterations.

PMID- 12197462
TI  - Any DNA to declare? Regulating offshore access to genetic enhancement.

PMID- 12197463
TI  - DNA-based identity testing and the future of the family: a research agenda.

PMID- 12197464
TI  - The routinization of prenatal testing.

PMID- 12197465
TI  - The genetic revolution at work: legislative efforts to protect employees.

PMID- 12197466
TI  - Genetics and privacy.

PMID- 12197467
TI  - Use and disclosure of health information in genetic research: weighing the impact
      of the new federal medical privacy rule.

PMID- 12197468
TI  - Informed consent in the military: fighting a losing battle against the anthrax
      vaccine.

PMID- 12197469
TI  - Arteriogenesis, a new concept of vascular adaptation in occlusive disease.
AB  - The formation of collateral arteries as a process adaptive to arterial occlusion
      is now called 'arteriogenesis' to emphasize the difference to angiogenesis, the
      formation of capillaries by sprouting from pre-existent ones (W. Schaper, I.
      Buschmann. Cardiovasc Res 1999; 43: 835-7; I. Buschmann, W. Schaper. J Pathol
      2000; 190: 338-42; D. Scholz et al. Virchows Arch 2000; 436: 257-70). The
      differences are that collaterals develop from pre-existing arterioles and that
      circulating monocytes adhere to endothelium that had been activated by the high
      shear stress generated by the large pressure differences between perfusion
      territories. Monocytes are the major producers of growth factors and of
      proteolytic enzymes that enable smooth muscle cells to migrate and divide. The
      nature of the growth factors remains uncertain. Neither FGF-1/2 nor VEGF is
      expressed on the transcriptional or translational level in collaterals proper and
      in the tissue surrounding them. Only FGF receptor 1 has a brief window of
      upregulation shortly after arterial occlusion. While transgenic overexpression of
      FGF-1 increases number and branching of arterioles, targeted disruption of FGF
      1/2 does not negatively influence arteriogenesis. Cytokines that attract
      monocytes or prolong the life span of monocytes (MCP-1, GM CSF) are strong
      arteriogenic factors. Collateral vessels exhibit the same morphology whether they
      had formed in the heart, limbs or brain or in dogs, rabbits or mouse. They are
      tortuous because they also increase lengthwise in a restricted space. In animals
      larger than the mouse, they develop an intima, and initially, many arterioles
      participate in arteriogenesis, but only a few mature into large arterial channels
      which, when arterial occlusion had proceeded slowly enough, can replace the
      occluded artery to a significant proportion. Therapy with a single growth factor
      in animals with occluded femoral arteries significantly increases the speed of
      arteriogenesis but does not significantly increase the level of adaptation. It
      appears that the mastergene for arteriogenesis still awaits discovery.

PMID- 12197470
TI  - Multiple angiogenesis stimulators in a single malignancy: implications for anti
      angiogenic tumour therapy.
AB  - Anti-angiogenesis is likely to develop into a novel therapeutic approach for
      patients with solid malignancies. Most current clinical trials evaluate anti
      angiogenic drugs aimed primarily against single angiogenesis stimulators. Here,
      we show that a single solid malignancy, i.e., a human embryonal rhabdomyosarcoma,
      produces in vivo at least three biologically active angiogenesis stimulators
      (vascular endothelial growth factor, basic fibroblast growth factor and
      interleukin-8). This suggests that tumour angiogenesis results from the activity
      of multiple, rather than a single angiogenesis stimulator(s). We, furthermore,
      show that a combination of anti-angiogenic drugs is more effective in inhibiting
      tumour-induced endothelial cell growth than a single agent. Our results imply
      that clinical anti-angiogenic strategies for the treatment of solid malignancies
      may be most effective when multiple rather than single antiangiogenic drugs are
      used.

PMID- 12197471
TI  - Statin-AE: a novel angiostatin-endostatin fusion protein with enhanced
      antiangiogenic and antitumor activity.
AB  - The combination of angiostatin and endostatin has been shown to have synergistic
      antiangiogenic and antitumor effects when the genes for these proteins are
      delivered to tumor cells by retroviral gene transfer. Here we report the
      construction of a murine angiostatin-endostatin fusion gene (Statin-AE) which
      shows enhanced antiangiogenic activity on human umbilical vein endothelial cell
      (HUVEC) tube formation in vitro compared with angiostatin or endostatin alone.
      Similarly, the fusion gene demonstrates antiangiogenic effects in vivo and
      antitumor activity in a B16F10 melanoma model when co-delivered by retroviral
      packaging cell inoculation in mice. The fusion gene demonstrates significantly
      greater inhibition of tumor growth compared with angiostatin, endostatin or the
      combination of genes.

PMID- 12197472
TI  - Fibrin fragment E stimulates the proliferation, migration and differentiation of
      human microvascular endothelial cells in vitro.
AB  - Various factors involved in haemostasis also regulate the development of new
      blood vessels by a process called angiogenesis. Enzymatic cleavage of fibrin
      yields a variety of fibrin degradation products, particularly in areas of intense
      angiogenesis such as in healing wounds and active atherosclerotic plaques. One of
      these, fibrin fragment E (FnE), is a potent angiogenic factor in the chick
      chorioallantoic membrane assay of angiogenesis. Here, we extend these studies to
      show that FnE stimulates the proliferation, migration and differentiation of
      human dermal microvascular endothelial cells (HuDMECs) in vitro, both in the
      absence and presence of such additional endothelial growth factors as vascular
      endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF). We
      also show that these stimulatory effects occur at concentrations of the protein
      known to be present in angiogenic tissues in vivo. FnE enhanced the angiogenic
      effects of VEGF or bFGF, indicating a possible synergy between the signalling
      pathways used by these three angiogenic factors.

PMID- 12197473
TI  - Effect of glycation on basic fibroblast growth factor induced angiogenesis and
      activation of associated signal transduction pathways in vascular endothelial
      cells: possible relevance to wound healing in diabetes.
AB  - Ineffectual wound healing in hyperglycaemic patients suffering from diabetes
      mellitus is characterised by a reduction in capillary reformation (angiogenesis).
      Basic fibroblast growth factor (FGF-2) is secreted by fibroblasts, macrophages
      and in particular endothelial cells (EC) in response to tissue injury and is
      important in promotion of neovascularisation. Recently, glycation of FGF-2 has
      been shown to significantly reduce its activity in vitro. We have examined the
      kinetics of FGF-2 glycation and compared its ability with that of native FGF-2 to
      activate mitogenesis, capillary formation and associated signal transduction in
      bovine aortic EC (BAEC). FGF-2 was exposed to 0.25 M glucose-6-phosphate (G-6-P)
      for 24-72 h and the degree of glycation determined by matrix assisted laser
      desorption ionisation mass spectrometry. Native FGF-2 was heterogeneous with Mw
      in the range 15,153.6-17,903 Da. After 24 h incubation with G-6-P there was
      evidence of glycation, and the mass increase corresponded to addition of 2.7 mol
      of G-6-P residues; after 48 h, 4 mol sugar was added and this increased to 8.7
      after 72 h. Dimerisation of FGF-2 was observed after 72 h of treatment. Induction
      of mitogenesis in BAEC was significantly reduced by 25%-40% after treatment for
      48-96 h with glycated (24 h) FGF-2 (gFGF-2; 100 pg/ml-5 ng/ml; P < 0.05), whilst
      capillary tubule formation was significantly reduced by between 60% and 90% (100
      pg/ml-1 ng/ml; P < 0.05) after 5 days compared to native FGF-2. Subsequent
      investigation of the signal transduction molecules associated with mitogenesis
      showed a reduction in FGF-2 induced tyrosine phosphorylated proteins of
      approximate Mw 20-150 kDa between 10 min and 24 h, in particular, mitogen
      activated protein kinase (MAPK)/early response kinase (ERK-1, ERK-2), after
      glycation. To determine the reason for reduced angiogenic activity of gFGF-2, we
      compared its binding characteristics to that of native FGF-2. Total binding of
      gFGF-2 to the cell surface was significantly reduced in BAEC analysed by FACS
      compared to native FGF-2 (P < 0.05). Further investigation using 125I-labelled
      differentially washed samples, demonstrated a significant reduction in gFGF-2
      binding to the high affinity tyrosine kinase receptor (46%) compared to native
      FGF-2. In summary, glycation of FGF-2 in vitro occurs rapidly within 24 h in the
      presence of elevated levels of G-6-P. Glycation caused a significant reduction in
      the ability of FGF-2 to bind to the tyrosine kinase receptor and activate signal
      transduction pathways responsible for both mitogenesis and capillary formation in
      BAEC. These results could help to explain the mechanism behind impaired wound
      healing in patients with diabetes mellitus.

PMID- 12197474
TI  - cDNA microarray analysis of the gene expression profile of VEGF-activated human
      umbilical vein endothelial cells.
AB  - Vascular endothelial growth factor (VEGF) is one of the most important factors
      that stimulate angiogenesis and vascular permeability. To clarify the role of
      VEGF, we analysed a human cDNA chip containing 7267 human genes to identify genes
      induced by VEGF in human umbilical vein endothelial cells (HUVECs). One hundred
      thirty-nine cDNAs, including ninety-nine previously known and forty poorly
      characterized or novel sequences, were increased more than two-fold by VEGF
      within twenty-four hours of stimulation. Among them, only five are known to
      regulate angiogenesis: cyclooxygenase 2 (COX2), heparin-binding epidermal growth
      factor-like growth factor, early growth response 1 (EGR 1), CYR61, and
      angiopoietin 2. Fifty-three genes induced within the first two hours were thought
      to be directly induced by VEGF. Of these, Down syndrome candidate region 1
      (maximum induction = 6.1-fold) was the most profoundly induced, followed by Mifl
      (KIAA0025; 5.5-fold), COX2 (4.7-fold), EGR 3 (3.7-fold), EGR 2 (3.2-fold),
      bactericidal/permeability-increasing protein (3.1-fold), and CD1B antigen, b
      polypeptide (3.1-fold). In addition to the genes mentioned above, there were many
      poorly characterized or novel genes induced by VEGF. Further analysis of these
      genes may aid in the elucidation of the molecular mechanisms of angiogenesis or
      vascular permeability stimulated by VEGF.

PMID- 12197475
TI  - Hirudo medicinalis: a new model for testing activators and inhibitors of
      angiogenesis.
AB  - An increasing body of evidence indicates that in the leech Hirudo medicinalis the
      angiogenic process is finely regulated and coordinated by the botryoidal tissue.
      In this paper we provide evidence on the involvement of botryoidal tissue cells
      in angiogenesis induced in H. medicinalis by a variety of stimuli including
      surgical wounds or the administration of modulators of neovascularization.
      Interestingly, we show that either human activators of vascular cell growth, or
      anti-angiogenic peptides like angiostatin and endostatin, or the drug mitomycin,
      can induce a prompt biological response in H. medicinalis. We show as well that
      angiogenesis in this invertebrate shares a surprising degree of similarity with
      neovascularization in vertebrates, both at the biochemical and cellular levels,
      because it involves similar growth factors/growth factor receptors, and relies on
      analogous cell-cell or cell-matrix interactions. For these reasons we suggest
      that H. medicinalis can be used as a reproducible model for testing activators or
      inhibitors of angiogenesis, and for investigating the biochemical,
      ultrastructural and cellular processes involved in new vessel formation.

PMID- 12197476
TI  - Distinct regulation of genes by bFGF and VEGF-A in endothelial cells.
AB  - A finely tuned balance of angiogenic inhibitors and inducers controls the
      activity of angiogenesis characterized by proliferation, migration and
      differentiation of endothelial cells. Among many angiogenic factors, basic
      fibroblast growth factor (bFGF) was first identified to be angiogenic whereas
      vascular endothelial growth factor A (VEGF-A) is an endothelial cell specific
      mitogen. In addition to being a specific mitogen, VEGF-A is also known as a
      vascular permeability factor. The majority of growth factors transduce their
      mitogenic signals from cell surface to nucleus where gene expression occurs.
      Whether these ligands utilize a distinct or a common molecular pathway to exert
      their biological effects on human endothelial cells remains elusive. We thus
      studied the expression profile of 884 human genes under the influence of either
      bFGF or VEGF-A alone in the context of human endothelial cells. A total of ninety
      four genes were differentially regulated by more than two folds. The expression
      patterns of 32 genes are similar between the treatment of either factor alone
      whereas those of the remaining 62 genes are only regulated by one but not the
      other factor. Their function in the control of angiogenesis will be discussed and
      apoptotic signaling in the regulation of angiogenesis is also implicated.

PMID- 12197477
TI  - Psychiatric reform in Europe. Proceedings of a conference. Bonn, Germany, 22-23
      November 2000.

PMID- 12197479
TI  - Anti-IgE antibody for the treatment of allergic asthma.

PMID- 12197480
TI  - Is BRCA1 associated with familial breast cancer in India?

PMID- 12197481
TI  - How much do we know about retinoid-regulated genes?

PMID- 12197482
TI  - Is p53 a breast cancer gene?

PMID- 12197483
TI  - A fly with an ointment: Bcl-2 as an anti-mutator in tumors.

PMID- 12197485
TI  - Apoptosis in colorectal tumors: does it help tumors metastasize?

PMID- 12197484
TI  - Chemotherapeutic targeting of p53.

PMID- 12197487
TI  - Anxiogenic, not psychotogenic, properties of the partial inverse benzodiazepine
      receptor agonist FG 7142 in man.

PMID- 12197490
TI  - ACOG committee opinion. Follow-up of abnormal screening mammography. Number 272,
      May 2002. American College of Obstetricians and Gynecologists.
AB  - Screening mammography facilitates the early diagnosis of breast carcinoma in
      women. Timely follow-up can optimize the diagnosis and treatment of women with
      abnormal screening test results. When test results reveal that additional studies
      are needed, no barriers should prohibit testing during the screening mammography
      visit.

PMID- 12197486
TI  - Is caspase-8 a neuroendocrine lung tumor suppressor?

PMID- 12197489
TI  - ACOG practice bulletin. Diagnosis and treatment of cervical carcinomas. Number
      35, May 2002. American College of Obstetricians and Gynecologists.
AB  - Invasive cervical carcinoma, once the most common reproductive-tract cancer in
      the United States, has recently fallen to the rank of third most common.
      Globally, cervical cancer is a major health problem, with a yearly incidence of
      371,000 cases and an annual death rate of 190,000. The International Federation
      of Gynecology and Obstetrics (FIGO) recently revised its staging criteria. In
      addition, new evidence has documented conclusively that survival rates for women
      with cervical cancer improve when radiotherapy is combined with cisplatin-based
      chemotherapy. This document will describe staging criteria and treatment for
      cervical carcinoma. For practical purposes, it will focus on the squamous and
      adenocarcinoma histologies only.

PMID- 12197491
TI  - ACOG committee opinion. Antenatal corticosteroid therapy for fetal maturation.
      American College of Obstetricians and Gynecologists.
AB  - The National Institute of Child Health and Human Development and the Office of
      Medical Applications of Research of the National Institutes of Health convened
      consensus conferences in 1994 and 2000 that recommended giving a single course of
      corticosteroids to all pregnant women between 24 and 34 weeks of gestation who
      are at risk of preterm delivery within 7 days. Because of insufficient scientific
      evidence, the consensus panel also recommended that repeat corticosteroid
      courses, including so-called "rescue therapy," should not be routinely used but
      should be reserved for women enrolled in clinical trials. Betamethasone and
      dexamethasone have been most widely studied and have generally been the preferred
      corticosteroids for antenatal treatment to accelerate fetal organ maturation. The
      American College of Obstetricians and Gynecologists' Committee on Obstetric
      Practice supports the conclusions of the consensus conferences.

PMID- 12197492
TI  - Deep brain stimulation for psychiatric disorders.

PMID- 12197493
TI  - A new mode of percutaneous upper thoracic phenol sympathicolysis: report of 50
      cases.

PMID- 12197494
TI  - Are nonfunctioning pituitary adenomas extending into the cavernous sinus
      aggressive and/or invasive?

PMID- 12197495
TI  - Remote cerebellar hemorrhage after supratentorial surgery.

PMID- 12197496
TI  - Management of spontaneous cerebellar hematomas: a prospective treatment protocol.

PMID- 12197497
TI  - Timing of aneurysm surgery in subarachnoid hemorrhage: a systematic review of the
      literature.

PMID- 12197498
TI  - Editorial: 100 years of epidemiology at the Pan American Health Organization.

PMID- 12197499
TI  - Case definition. Salmonellosis.

PMID- 12197500
TI  - Dengue in Brazil: current situation and prevention and control activities.

PMID- 12197501
TI  - Introduction to social epidemiology.

PMID- 12197502
TI  - A glossary for social epidemiology.

PMID- 12197503
TI  - Gene banks and blanket consent.

PMID- 12197504
TI  - The meaning of caring for patients on a long-term psychiatric ward as narrated by
      formal care providers.

PMID- 12197505
TI  - Visibility amplification of intestinal intraepithelial lymphocytes.

PMID- 12197507
TI  - Pathologic quiz case: quadriplegic patient with recurrent paraspinal mass.

PMID- 12197506
TI  - Pathologic quiz case: a pancreatic mass in a 44-year-old woman.

PMID- 12197508
TI  - Pathologic quiz case: a 68-year-old woman with bluish discoloration of the skin
      of the breast.

PMID- 12197509
TI  - Pathologic quiz case: a 9-year-old boy with headache, visual changes, and an
      occipital mass.

PMID- 12197510
TI  - Inhalation of anthrax: gross autopsy findings.

PMID- 12197511
TI  - "Ossifying-type" mammary calcifications.

PMID- 12197512
TI  - Transformation of follicular lymphoma to acute lymphoblastic leukemia.

PMID- 12197513
TI  - Biophysical limitation of cell elongation in cereal leaves.
AB  - Grass leaves grow from the base. Unlike those of dicotyledonous plants, cells of
      grass leaves expand enclosed by sheaths of older leaves, where there is little or
      no transpiration, and go through developmental stages in a strictly linear
      arrangement. The environmental or developmental factor that limits leaf cell
      expansion must do so through biophysical means at the cellular level: wall
      yielding, water uptake and solute supply are all candidates. This Botanical
      Briefing looks at the possibility that tissue hydraulic conductance limits cell
      expansion and leaf growth. A model is presented that relates pathways of water
      movement in the elongation zone of grass leaves to driving forces for water
      movement and to anatomical features. The bundle sheath is considered as a crucial
      control point. The relative importance of these pathways for the regulation of
      leaf growth and for the partitioning of water between expansion and transpiration
      is discussed.

PMID- 12197514
TI  - Secretory trichomes, a substitutive floral nectar source in Lundia A. DC.
      (Bignoniaceae), a genus lacking a functional disc.
AB  - This is the first report of corolla-borne secretory trichomes that substitute in
      role for a non-functional disc in a species of the neotropical genus Lundia A.
      DC. (Bignoniaceae). The floral biology and flowering phenology of Lundia cordata
      were investigated at two remnants of tropical rainforest in northeastern Brazil.
      This species is a typically omithophilous liana, with reddish, tubular, scentless
      flowers. The flowers are resupinate, protandrous and last for 2 d. There is a
      vestigial non-functional perigynous disc and nectar is secreted by glandular
      trichomes distributed along the internal surface of the corolla. The nectar is
      stored at the base of the corolla tube, thus showing secondary nectar
      presentation. The nectariferous trichomes are multi-cellular, uniseriate, with a
      basal foot cell rooting in the epidermis, one neck cell, and a glandular head
      with 13 cells on average. Three species of hummingbirds (Amazilia fimbriata,
      Eupetomena macroura and Phaethornis pretrei) serve as pollinators. Phaethornis
      ruber, Xylocopa bees, wasps and diurnal moths are considered nectar thieves.

PMID- 12197515
TI  - Nodule ultrastructure and initial growth of Anadenanthera peregrina (L.) Speg.
      var. falcata (Benth.) altschul plants infected with rhizobia.
AB  - The anatomy and ultrastructure of root nodules of Anadenanthera peregrina var.
      falcata (Leguminosae-Mimosoideae) were analysed, as was plant growth. To ensure
      that nodules developed, seedlings were inoculated with a mixture of six strains
      of rhizobia. Nodules were produced that differed in appearance-and probably also
      effectiveness-but their structure was similar and they showed characteristics
      typical of indeterminate nodules, such as persistent meristematic tissue and a
      gradient of cells at different stages of development. Many starch grains were
      present in inner cortex cells and interstitial cells of infected tissue. Infected
      cells were densely packed with bacteroids, which contained many poly-beta
      hydroxybutyrate granules. The high incidence of these granules, together with
      high levels of starch accumulation in interstitial cells, suggested low N2
      fixation efficiency of the rhizobia isolates used for inoculation. In the
      symbiosomes of early-senescent infected cells, reticulum-like structures, small
      vesicles and a fibrillar material were observed; these may be related to
      bacteroid degradation. In the cytoplasm of late-senescent infected cells, many
      vesicles and membrane-like structures were observed, probably associated with
      membrane degradation of bacteroids and peribacteroids. The total biomass of
      plants inoculated with rhizobia was low and their xylopodia and shoots had low
      levels of N compared with noninoculated plants fertilized with ammonium nitrate.
      However, inoculated plants did not show N-deficiency symptoms and grew better
      than non-inoculated plants without N fertilization. These growth results,
      together with ultrastructural observations of nodules, suggest that nitrogen
      fixation of rhizobia isolates associated with Anadenanthera peregrina var.
      falcata roots is poor.

PMID- 12197516
TI  - Quantifying above- and below-ground growth responses of the western Australian
      oil mallee, Eucalyptus kochii subsp. plenissima, to contrasting decapitation
      regimes.
AB  - Resprouting in the oil mallee, Eucalyptus kochii Maiden & Blakely subsp.
      plenissima Gardner (Brooker), involves generation of new shoots from preformed
      meristematic foci on the lignotuber. Numbers of such foci escalated from 200 per
      lignotuber in trees aged 1 year to 3,000 on 4- to 5-year-old trees. Removal of
      shoot biomass by decapitation 5 cm above ground in summer (February) or spring
      (October) resulted in initiation of 140-170 new shoots, but approx. 400 shoots
      were induced to form if crops of new shoots were successively removed until
      sprouting ceased and rootstocks senesced. Initially, the new shoot biomass of
      regenerating coppices increased slowly and the root biomass failed to increase
      appreciably until 1.7-2.5 years after cutting. Newly cut trees showed loss of
      fine root biomass, and structural roots failed to secondarily thicken to the
      extent shown by uncut trees. After 2 years, the biomass of shoots of coppiced
      plants was only one-third that of uncut control trees and shoot:root dry mass
      ratios of coppiced plants were still low (1.5-2.0) compared with those of the
      controls (average ratio of 3.1). Spring cutting promoted quicker and greater
      biomass recovery than summer cutting. Starch in below-ground biomass fell quickly
      following decapitation and remained low for a 12-18 month period. Utilization of
      starch reserves in naturally regenerating coppices was estimated to provide only
      a small proportion of the dry matter accumulated in new shoots. Results are
      discussed in relation to their impact on coppicing ability of the species under
      natural conditions or when successively coppiced for shoot biomass production.

PMID- 12197517
TI  - Phenotypic plasticity and integration in response to flooded conditions in
      natural accessions of Arabidopsis thaliana (L.) Heynh (Brassicaceae).
AB  - Flood response is a crucial component of the life strategy of many plants, but it
      is seldom studied in non-flooded tolerant species, even though they may be
      subjected to stressful environmental conditions. Phenotypic plasticity in
      reaction to environmental stress affects the whole plant phenotype and can alter
      the character correlations that constitute the phenotypic architecture of the
      individual, yet few studies have investigated the lability of phenotypic
      integration to water regime. Moreover, little has been done to date to quantify
      the sort of selective pressures that different components of a plant's phenotype
      may be experiencing under contrasting water regimes. Genetic differentiation and
      phenotypic plasticity at the single-trait and multivariate levels were
      investigated in 47 accessions of the weedy plant Arabidopsis thaliana, and the
      relationship of plastic characters to reproductive fitness was quantified.
      Results indicate that these plants tend to be highly genetically differentiated
      for all traits, in agreement with predictions made on the basis of environmental
      variation and mating system. Varied patterns of apparent selection under flooded
      and non-flooded conditions were also uncovered, suggesting trade-offs in
      allocation between roots and above-ground biomass, as well as between leaves and
      reproductive structures. While the major components of the plants' multivariate
      phenotypic architecture were not significantly affected by environmental changes,
      many of the details were different under flooded and non-flooded conditions.

PMID- 12197518
TI  - Nuclear DNA C-values in 30 species double the familial representation in
      pteridophytes.
AB  - Nuclear DNA C-values and genome size are important biodiversity characters with
      fundamental biological significance. Yet C-value data for pteridophytes, a
      diverse group of vascular plants with approx. 9000 extant species, remain scarce.
      A recent survey by Bennett and Leitch (2001, Annals of Botany 87: 335-345) found
      that C-values were reported for only 48 pteridophyte species. To improve
      phylogenetic representation in this group and to check previously reported
      estimates, C-values for 30 taxa in 17 families were measured using flow cytometry
      for all but one species. This technique proved generally applicable, but the ease
      with which C-value data were generated varied greatly between materials.
      Comparing the new data with those previously published revealed several large
      discrepancies. After discounting doubtful data, C-values for 62 pteridophyte
      species remained acceptable for analysis. The present work has increased the
      number of such species' C-values by 93 %, and more than doubled the number of
      families represented (from 10 to 21). Analysis shows that pteridophyte C-values
      vary approx. 450-fold, from 0-16 pg in Selaginella kraussiana to 72.7 pg in
      Psilotum nudum var. gasa. Superimposing C-value data onto a robust phylogeny of
      pteridophytes suggests some possible trends in C-value evolution and highlights
      areas for future work.

PMID- 12197519
TI  - Floral and vegetative morphometrics of five Pleurothallis (Orchidaceae) species:
      correlation with taxonomy, phylogeny, genetic variability and pollination
      systems.
AB  - Morphometric analyses of vegetative and floral characters were conducted in 21
      populations of five Pleurothallis (Orchidaceae) species occurring in Brazilian
      'campo rupestre' vegetation. A phylogenetic analysis of this species group was
      also carried out using nuclear ribosomal DNA internal transcribed spacers (ITS1
      and ITS2). Results of the ordination and cluster analyses agree with species'
      delimitation revealed by taxonomic and allozyme studies. The groups formed in
      ordination analysis correspond to the pollinator groups determined in a previous
      pollination study. Relationships among the species in the cluster analysis using
      only vegetative characters are similar to those found in a previous allozyme
      study, but those indicated by cluster analysis using only floral characters
      differ. These results support the hypothesis that floral similarities are due to
      convergence driven by similar pollination mechanisms, and therefore floral traits
      may not be good indicators of phylogenetic relationships in this group. The
      results of the phylogenetic analysis support this conclusion to some extent.
      There is no correlation between genetic (allozyme) and morphological variability
      in the populations nor in the way this variability is distributed among
      conspecific populations. We describe a new subspecies of Pleurothallis ochreata
      based on differences in vegetative and chemical characters as well as geographic
      distribution. Absence of differentiation in floral characters, attraction of the
      same pollinator species, interfertility and genetic similarity support the
      argument for subspecific rather than specific status.

PMID- 12197520
TI  - Assessment of the validity of the sections in Musa (musaceae) using AFLP.
AB  - Musa L. (Musaceae) is currently separated into five sections (Musa. Rhodochlamys,
      Callimusa, Australimusa and Ingentimusa) based on chromosome numbers and
      morphological characters. However, the validation of this classification system
      is questioned due to the common occurrence of hybridizations across sections and
      the system not accommodating anomalous species. This study employed amplified
      fragment length polymorphism (AFLP) in a phenetic examination of the
      relationships among four sections (material of sect. Ingentimusa was not
      available) to evaluate whether their genetic differences justify distinction into
      separate groups. Using eight primer combinations, a total of 276 bands was
      scored, of which 275 were polymorphic. Among the monomorphic bands, 11 unique
      markers were identified that revealed the distinct separation of the 11
      chromosome species from the 10-chromosome species. AFLP results suggest that
      species of sect. Rhodochlamys should be combined into a single section with
      species of sect. Musa, and likewise for species of sect. Australimnusa to be
      merged with those of sect. Callimusa.

PMID- 12197521
TI  - An investigation of the seasonal pattern of mannitol content in deciduous and
      evergreen species of the oleaceae growing in northern Sicily.
AB  - In several species of the Oleaceae, mannitol, already present at considerable
      levels, accumulates in response to stress. This family comprises both deciduous
      and evergreen species, and we investigated the role of mannitol in deciduous
      malacophyll and evergreen sclerophyll species growing under the same conditions
      in the field. The relationship between mannitol content and changes in rainfall
      or temperature was also studied. The mannitol content of leaves of Fraxinus ornus
      L., F. angustifolia Vahl., Olea europaea L. and Phillyrea media L. was determined
      by gas chromatography. Leaf samples were collected once a month for 1 year. In
      the two ash species, the seasonal pattern of mannitol content appeared the same:
      a gradual increase in spring, peaking in summer, followed by a gradual decrease.
      The mannitol content was similar in both species, ranging between 260 and 720
      micromol g(-1) d. wt. The seasonal pattern of mannitol content in Olea and
      Phillyrea was similar for both species, but unlike that of Fraxinus did not show
      a summer peak. Rainfall was negatively correlated with the seasonal increase of
      mannitol content in ash. Mannitol content increased gradually during drought,
      reaching a maximum value at the end of the dry season. Temperature did not have a
      direct influence on mannitol content. In Olea and Phillyrea, variations in
      mannitol content were poorly correlated with rainfall or temperature, indicating
      that mannitol does not have a primary role in the response of these species to
      the hot, dry summer conditions.

PMID- 12197522
TI  - Influence of litter and weather on seedling recruitment in a mixed oak-pine
      woodland.
AB  - The effects of regular litter removal and annual variation in temperature and
      precipitation on seedling recruitment of species differing in their seed size and
      mode of dispersal were studied in a 16-year (1984-1999) experiment in a mixed oak
      pine wood in southern Poland. Litter was the most important factor in determining
      spatial variability in seedling recruitment, whereas differences in climatic
      conditions among years, especially temperature fluctuations in late winter and
      early spring, determined the temporal variability in seedling recruitment.
      Compared with control plots, significantly more new individuals of bryophytes and
      seedlings as well as a number of new species of vascular plants were noted in the
      litter-removal plots over the 16-year study. Litter strongly impeded seedling
      emergence of small-seeded species. The negative effect of litter on seedling
      recruitment of large-seeded species and the recruitment of new shoots in species
      growing clonally was much weaker. There was a significant positive correlation
      between the numbers of seedlings in the litter-removal and control plots and
      temperatures in January to March. In the litter-removal plots this mainly
      affected small-seeded species. Seedling recruitment was less consistently related
      to variation in precipitation. Positive relationships were found only between the
      number of seedlings of large-seeded species in the litter-removal plots and
      precipitation in July of the current year and in September of the previous year,
      and between the number of seedlings in the control plots and precipitation in
      September and November of the previous year.

PMID- 12197523
TI  - Non-invasive localization of thymol accumulation in Carum copticum (Apiaceae)
      fruits by chemical shift selective magnetic resonance imaging.
AB  - Magnetic resonance imaging was used to localize the site of essential oil
      accumulation in fruit of Carum copticum L. (Apiaceae). A chemical shift method is
      described that utilized the spectral properties of the aromatic monoterpene
      thymol, the major component of the essential oil, to image thymol selectively.
      The presence of essential oil secretory structures in the fruit and an essential
      oil containing a high proportion of thymol were confirmed with optical microscopy
      and gas chromatography-mass spectrometry, respectively. Selective imaging of
      whole C. copticum fruits showed that thymol accumulation was localized to the
      secretory structures (canals) situated in the fruit wall. The technique was
      considered non-invasive as the seeds used in the imaging experiments remained
      intact and viable.

PMID- 12197524
TI  - Heat-tolerant flowering plants of active geothermal areas in Yellowstone National
      Park.
AB  - A broad survey of most of the major geyser basins within Yellowstone National
      Park (Wyoming, USA) was conducted to identify the flowering plants which tolerate
      high rhizosphere temperatures (> or = 40 degrees C) in geothermally heated
      environments. Under such conditions, five species of monocots and four species of
      dicots were repeatedly found. The predominant flowering plants in hot soils (>40
      degrees C at 2-5 cm depth) were grasses, primarily Dichanthelium lanuginosum.
      Long-term (weeks to months) rhizosphere temperatures of individual D. lanuginosum
      above 40 degrees C were recorded at several different locations, both in the
      summer and winter. The potential role of heat shock proteins (HSPs) in the
      apparent adaptation of these plants to chronically high rhizosphere temperatures
      was examined. Antibodies to cytoplasmic class I small heat shock proteins (sHSPs)
      and to HSP101 were used in Western immunoblot analyses of protein extracts from
      plants collected from geothermally heated soils. Relatively high levels of
      proteins reacting with anti-sHSP antibodies were consistently detected in root
      extracts from plants experiencing rhizosphere temperatures above 40 degrees C,
      though these proteins were usually not highly expressed in leaf extracts from the
      same plants. Proteins reacting with antibodies to HSP101 were also present both
      in leaf and root extracts from plants collected from geothermal soils, but their
      levels of expression were not as closely related to the degree of heat exposure
      as those of sHSPs.

PMID- 12197525
TI  - Structural and ultrastructural analysis of Solanum lycopersicoides protoplasts
      during diploid plant regeneration.
AB  - Light, fluorescence and electron microscopy were used to analyse the structural
      properties of protoplasts obtained from established suspension culture of Solanum
      lycopersicoides Dun, composed of meristematic cell aggregates. Four types of
      protoplasts were distinguished immediately after isolation: (1) mononuclear; (2)
      polynuclear, (3) anuclear and (4) homogeneous protoplasts. Only mononuclear
      protoplasts were capable of complete cell wall regeneration and mitotic division.
      Other types of protoplasts were eliminated during culture. Three phases were
      distinguished in the developing protoplast culture: (1) the elimination phase
      during which protoplasts damaged during isolation underwent complete degradation;
      (2) a phase of intense division during which both mitotic cell division and
      amitotic nuclear division took place; and (3) a stabilization phase leading to
      the formation of suspension culture. The cell suspension culture obtained from
      protoplasts was capable of regenerating diploid plants.

PMID- 12197526
TI  - Role of within-individual variation in capitulum size and achene mass in the
      adaptation of the annual Centaurea eriophora to varying water supply in a
      Mediterranean environment.
AB  - To clarify the adaptive value of variation in capitulum size and achene mass,
      plants of Centaurea eriophora were studied in a glasshouse and in a natural
      population. C. eriophora plants consist of a basal leaf rosette from which an
      erect stem grows, with lateral branches of various orders ending in capitula of
      different orders. Primary, secondary and tertiary capitula are comparable in size
      and they produce similar numbers of achenes, which are similar in weight (large
      achenes). These capitula are formed during April, May and early June, and
      constitute the normal or primary flowering. Following ripening of tertiary
      capitula, leaves senesce, but, later during June and the first half of July, a
      secondary flowering of a variable number of smaller capitula may occur if wet
      conditions persist for longer than usual. Plants that have almost senesced
      develop small lateral branches 1-2 cm long bearing a few small leaves and ending
      in a capitulum about half the diameter of capitula from the primary flowering
      period. The number of achenes produced in these capitula (small achenes) and
      their weight are 70 and 30% less, respectively, than those of capitula formed
      during primary flowering. These reductions appear to result from restricted
      availability of resources. Large and small achenes have similar dispersal
      characteristics and possess similar germination potential. However, large achenes
      produce seedlings that are capable of emerging from greater burial depths,
      providing the resulting plants with a potential advantage. The normal flowering
      period coincides with the optimum time of year for flowering and fruiting in the
      south of Spain, and only if rainfall lasts longer than usual does secondary
      flowering occur. Secondary flowering extends the normal flowering and fruiting
      periods, thereby providing a supplementary crop of smaller, yet viable, fruits.
      It can be considered to be an adaptive response to the unpredictable
      Mediterranean climate, optimizing the use of available resources.

PMID- 12197527
TI  - Programmed cell death during embryogenesis in maize.
AB  - Programmed cell death (PCD) in plants is considered an integral part of
      development. Evidence of DNA fragmentation, occurring at specific sites and times
      during embryo formation in maize (Zea mays L.), was obtained using terminal
      deoxyribonucleotidyl transferase-mediated dUTP-fluorescein nick end labelling
      (TUNEL) and by genomic DNA ladder detection. During the crucial period of
      elaboration of the primary shoot and root axis (14-20 d after pollination), TUNEL
      positive nuclei are present in the scutellum, coleoptile, root cap and
      principally in the suspensor. Additional evidence of a form of programmed cell
      death occurring in these tissues comes from the detection of a DNA ladder. Upon
      completion of the differentiation process, all embryonic cells are TUNEL
      negative, indicating that possible programmed cell death events during maize
      embryogenesis are confined to structures or organs that do not contribute to the
      adult plant body.

PMID- 12197528
TI  - Changes of morphogenic competence in mature Pinus sylvestris L. buds in vitro.
AB  - The effects of season and cold storage on morphogenic competence in mature Pinus
      sylvestris buds were investigated. Peroxidase and polyphenol oxidase activity
      were measured as markers of oxidative metabolism. No growth in vitro was observed
      on explants detached from the end of January until the beginning of March.
      Brachioblasts, each with a couple of needles, formed on 11% of the buds without
      macrostrobili that were detached in early April and introduced immediately into
      culture. Of the explants detached in late July, 15% formed shoots with
      brachioblasts and needles. The lowest activity of peroxidase and polyphenol
      oxidase in pine buds was observed from the end of April until the beginning of
      June when morphogenic competence of tissues started to increase. Development of
      bud explants detached in January was achieved by cold storage for 5 months. Low
      polyphenol oxidase and peroxidase activity coincided with increased morphogenic
      potential. Results suggest that reduced or stable activity of peroxidase and
      polyphenol oxidase is associated with an increased ability of tissues to start
      growth in vitro.

PMID- 12197530
TI  - Predicted LET-spectra of HZE-particles for the Free Flyer Biostack Experiment on
      the long duration exposure facility mission.
AB  - The LDEF (long duration exposure facility) mission, scheduled for a launch on the
      Space Shuttle in 1981, will fly for about 9 months in a near-earth orbit with an
      inclination angle of 28 degrees. In this flight the Free Flyer Biostack
      Experiment has the objective of measuring the biological effects of individual
      heavy ions from cosmic radiation (HZE particles). This paper presents results of
      a calculation of LET-spectra in free space and within the absorber of the
      experiment. The calculation considers the geomagnetic shielding of the space
      craft against charged particles with low energies and the disintegration of the
      heavy ions within the absorbing material by fragmentation. For this mission the
      LET spectra turn out to differ from those of previous experiments. The steepness
      of the spectra changes significantly with LET and also with depth of absorber.

PMID- 12197531
TI  - A sclerocorneal electrode for the study of the characteristics of primate vision
      under condition of space flight.
AB  - We describe here a physiologically nonirritating sclerocorneal lens electrode of
      special design for making reproducible, low noise electroretinographic recordings
      on frogs and the rhesus monkey. The apparatus should be particularly useful in
      studying the effect of space flight factors on these responses in man.

PMID- 12197529
TI  - Recent radiobiological findings from spaceflight and ground-based studies--an
      overview.
AB  - With respect to radiation standards for manned space flight, we wish to address
      ourselves to the following topics that we consider pertinent for a realistic
      assessment of the risk to man when exposed to ionizing radiation under space
      flight conditions: 1) prediction and measurement of the spectra of the physical
      traits of cosmic radiation as a function of orbital parameters and the mass
      shielding of the spacecraft; 2) synergistic or antagonistic modification of
      radiation effects by dynamic flight conditions and by the space environment; 3)
      production of biological damage becoming manifest only long after exposure,
      especially to the heavy ions; and 4) demonstration of possibly specific
      radiobiological mechanisms for the densely ionizing heavy-ion component of the
      cosmic radiation. Some recent work referring to these topics will be presented
      and discussed with emphasis on the high LET component of the cosmic radiation.

PMID- 12197532
TI  - [Preliminary study of vestibular balance in the primate under space flight
      conditions].

PMID- 12197533
TI  - Intestinal hydrogen and methane of men fed space diet.
AB  - Intestinal bacteria form two gases, hydrogen (H2) and methane (CH4), that could
      constitute a fire hazard in a closed chamber. So H2 and CH4 pass from the anus
      but these gases are also transported by the blood to the lungs and removed to the
      atmosphere. Several factors affect gas formation: 1) amount and kind of
      fermentable substrate; 2) abundance, types, and location of microflora; and 3)
      psychic and somatic conditions that affect the gut. We evaluated the first factor
      by studying men fed different diets and have also recorded influences of
      uncontrollable factors. One group of 6 men ate Gemini-type diet (S) and another
      received a bland formula (F), for 42 days. Breath and rectal gases were analyzed
      during the first and final weeks. Flatus gases varied widely within dietary
      groups but much more gas was generated with diet S than with F. In the first 12
      hour collection, subjects fed S passed 3 to 209 ml (ATAP) of rectal H2 (avg 52)
      and 24 to 156 ml (avg 69) from the lungs (assuming normal pulmonary ventilation).
      With F, these values were 0 to 3 ml (avg 1) and 6 to 36 ml (avg 20). Subjects
      were calmer during the second test. Gas production was lower with S than
      initially; F values were unchanged. Methane differed idiosyncratically,
      presumably due to differences in flora. Computed from 12-hour values, maximum
      potential daily H2 and CH4 are per man: for S, 730 ml and 382 ml; for F, 80 and
      222 ml. Volumes would be larger at reduced spacecraft and suit pressures.

PMID- 12197535
TI  - The problem of sterilizing a life-support system in biosatellite experiments over
      one year.
AB  - Special efforts are necessary to sterilize the life-support system for
      experimental animals in biosatellite experiments over one year. The energy
      requirements needed are relatively high and the energy which is available in
      biosatellites at the present time is a limiting factor, particularly in long-term
      experiments. It is shown that these difficulties are overcome by the selection of
      an appropriate experimental animal. Thus, it was possible to prepare a long-term
      satellite experiment.

PMID- 12197534
TI  - Current research on regenerative systems.
AB  - Multiple studies directed toward the development of a regenerative life support
      system have shown that easily synthesized organic compounds and microbiological
      materials are potentially capable of being used as foods for long-duration space
      missions. Animal feeding studies have supported these views. The organic
      compounds presently believed to offer the greatest potential are glycerol, simple
      glycerol derivatives such as triacetin, and formose sugars. Laboratory studies
      indicate that glycerol can be synthesized from formaldehyde which in turn is
      obtained by the direct catalytic oxidation of methane, a by-product of the
      Sabatier reaction used in spacecraft atmosphere control system. Formose sugars
      are derived from the self-condensation of formaldehyde. Mixtures of glycerol and
      triacetin have been shown to be suitable as a major component of diets fed to
      weanling rats for prolonged periods. These compounds do not exist as
      stereoisomers and therefore offer advantages over the formose sugars.
      Hydrogenomonas eutropha is the microbiological system under investigation. An
      automated system for the continuous autotrophic production of Hydrogenomonas
      bacteria is in operation, and the nutritional requirements for growth in the
      system using urea as a nitrogen source are being studied. Nutritional evaluation
      of Hydrogenomonas bacteria has shown they are capable of supplying the total
      protein requirement of growing rats for prolonged periods. The potential and
      problems of these regenerative systems and the prospects for the accomplishment
      of a totally regenerative food system will be discussed.

PMID- 12197536
TI  - Oxygen supply and carbon dioxide absorption in long-term life-support systems.
AB  - Long-term experiments with animals in space require a life-support system that
      provides optimal conditions of life at lowest energy demand. Experimental studies
      of different physicochemical and biological systems are compared. While such
      experiments are limited by energy requirements, it is possible to choose a
      certain system by comparing the exact energy balances of the different ecological
      systems.

PMID- 12197537
TI  - RBE values for fast neutrons in connection with estimates of the radiation burden
      in space.
AB  - Much data concerning radiation in space as a serious danger to astronauts can be
      obtained in laboratories on Earth. For different parameters we investigated the
      relative biological efficiency (RBE) of 14-MeV neutrons on mice, rats and guinea
      pigs (being wholly exposed). Also the mitosis inhibition for isolated cells was
      determined. The RBE values found were: for lethality in the LD50(30d)-region-
      about 2 (for mice, rats and guinea pigs); for reduction due to radiation of
      living weight of different animals--2 to 3; for reduction of small gut weight of
      rats and guinea pigs--2.5 and 2; for histological changes in blood and albumin
      serum (rats and guinea pigs)--about 2; for the highly sensible cells of the lense
      epithelium from eyes of rabbits--2.5; for the mitosis inhibition of HeLa cells-
      2.5. The apparatus for radiation tests is described and measuring methods are
      indicated. The radiation of the whole body of mice, rats and guinea pigs was
      determined by activating of MgCl2 solution filled into phantoms. By means of a
      computer, the depth-dose curve can be determined for larger biological objects.

PMID- 12197538
TI  - A radiation source for testing optical solar radiation effects.
AB  - This paper discusses the recent engineering developments incorporated in a new
      mercury injection lamp. The injection of mercury through one of the electrodes
      into the arc permits constructing a cooling system for electrodes and bulb. This
      results in a higher powered mercury lamp than previously known. The realized
      highest electrical input of 7.5 kw was given by our power supply; it is not the
      limitation of the lamp. To simulate solar radiation, it is necessary to have a
      lamp with a high radiance. The second interesting point is the variability of the
      spectral energy distribution. To improve the spectrum, perhaps to simulate solar
      spectral match, many elements can be added to the mercury. Most of the metals
      build fluid amalgams with mercury.

PMID- 12197539
TI  - Prediction of interindividual differences in radiosensitivity in mammals.
AB  - Prediction of individual radiosensitivity of mammals is of interest to
      radiobiology on the one hand and it is also important to the clinical use of
      radiation. The author has reported that there is a relationship between
      radiosensitivity in individual animals and its homeostatic activity that allows
      predicting individual radiosensitivity. In the present report, a phenomenon of
      metabolism was used to measure the homeostatic activity of an individual mouse
      DBA strain, 90 days old; that is, the metabolic rate was calculated from daily
      diet or water consumption, and body weight. Each mouse fasted completely for one
      day and the ratio between metabolic rates just before and just after the fast
      (value after fast/value before fast) was calculated to use as the index of
      homeostatic activity of each mouse. One week after fasting, the mice were exposed
      to X-rays of 500 R and the ratio of metabolic rates just before and just after
      exposure was calculated again. Ten days after exposure the mice were sacrificed
      and the spleens were fixed in Bouin's solution. After fixing, the splenic weight
      was measured and an endogenous spleen colony count (more than 1 mm diameter) was
      made, which was one response to radiation damage to the hematopoietic system. The
      results, summarized from several repeated experiments are given in the table
      below: [table: see text].

PMID- 12197540
TI  - Some results of radiobiological studies performed on Cosmos-110 biosatellite.
AB  - The experiment carried out on the Cosmos 110 biosatellite is a step further in
      radiobiological investigations performed in outer space and differs appreciably
      from flight experiments conducted on board the Vostok and Voskhod spacecraft. The
      difference lies, firstly, in the integral dose of cosmic radiation. According to
      the onboard dosimeter readings, it was 12 rad at an average dose rate of 500
      mrad/day during the biosatellite flight, whereas in previous biological flight
      experiments, as is well known, the total dose was below 80 mrad (on a five-day
      flight of Vostok 5) at a dose rate of 80 to 20 mrad/day. Secondly, during the
      biosatellite mission, cosmic radiation originated not from the primary cosmic
      radiation as was the case in the Vostok and Voskhod flights but mainly from the
      Earth's radiation belts. Thirdly, the duration of the Cosmos 110 flight was far
      longer than that of any previous mission: the effect of weightlessness lasted for
      about 22 days. The paper presents results of investigations performed on E. coli
      K-12 lambda lysogenic bacteria, Tradescantia microspores, dry seeds of higher
      plants, different Chlorella strains and an intact plant of Tradescantia paludosa.
      The biological effect of space flight factors was evaluated by various
      physiological, cytogenetic, genetic and microbiological techniques. Similar to
      previous experiments carried out on board the Vostok 3-6 spacecraft, tests with
      lysogenic bacteria revealed a statistically significant induction of moderate
      bacteriophage. The induction value was shown to lag behind the mission duration
      dependence level. This seems to be related to a change of inducibility properties
      of lysogenic bacteria and a reduction of the yield range of phages per bacterial
      cell. Other tests (duration of the latent period, formation pattern of phage
      components) indicated no significant differences between test and control objects
      (N.N. Zhukov-Verezhnikov, N.I. Rybakov, V.A. Kozlov et al.). A study of
      protective properties of chemical compounds of different types in relation to the
      bacteriophage induction demonstrated that preparations of the aminothiolic group
      produced a high antimutagenic effect (V.A. Kozlov, N.I. Rybakov et al.). A
      postflight cytological analysis of Tradescantia paludosa microspores indicated
      their changes of three types: chromosome aberrations, mitotic disturbances and
      disorders of growth processes in the cell. Examinations of dry seeds of wheat,
      barley, pine and other plants, as well as of Allium cepa bulbs, gave evidence of
      a diverse effect of space flight factors on both physiological processes and
      hereditary structures of the objects. In some cases an increased percentage of
      seed germination, stimulation of their growth and a significant increase of
      aberrations were found. An investigation of the occurrence frequency of visible
      mutations in reaction cell cultures of different Chlorella strains (LARG-1, LARG
      3 and others) showed no significant differences between the test and control
      material. Some cultures taken under a more detailed study indicated a delay with
      which cells entered the first sporulation and a greater amount of cells that
      divided into a lesser than usual number of autospores. In addition, test variants
      of the strains showed a slightly reduced survival of Chlorella cells. The
      reduction appeared to be statistically significant for the LARG-3 strain only
      (E.N. Vaulina et al.). A postflight examination of the appearance of the
      Tradescantia paludosa plant showed that it retained good turgor; its leaves were
      dark green and several bright flowers bloomed. No signs of its inhibition or
      etiolation were noted. As compared to the control, the test plant grew noticeably
      and the stem became crooked. Certain problems of biological indications of outer
      space are discussed.

PMID- 12197542
TI  - Studies of human adaptation to space flight effects under low-calorie diet
      conditions.
AB  - Experiments were performed to establish the activity and performance of man kept
      on a low-calorie (1800) diet and exposed to some space flight effects. The diet
      consisted of canned foods with an optimal proportion of basic nutrients and amino
      acids. Three series of experiments were carried out on 18 healthy male subjects.
      Each series involved pre- and post-test examinations and 15-day tests. The first
      series dealt with the effect of low-calorie diets as such; the second one covered
      the effect of low-calorie diets combined with bed rest; and the third series
      revealed the above effect aggravated by exposing test subjects to bed rest and
      acceleration. In the course of the experiments, the state of the central nervous
      and cardiovascular systems, the function of external respiration, the digestive
      function, the kinesthetic apparatus, metabolic processes and immunological
      resistance of the body were studied. In addition, test subjects underwent
      thorough clinical examinations. The paper presents results of the experiments.

PMID- 12197541
TI  - Discussion of a possible contamination of space with terrestrial life.
AB  - Theoretical considerations were made on what forces and energies affect a
      particle the size of a microorganism near the Earth and what conditions result
      for the particle. A transfer of terrestrial life to other celestial bodies seems
      impossible unless it is done by a spacecraft. This possibility cannot be excluded
      even after sterilization of the spacecraft on Earth, for in higher layers of the
      atmosphere the spacecraft could be contaminated again. In this case
      microorganisms would be subjected to a space flight where decompression is much
      slower initially than is the case on leaving the Earth's surface with the
      spacecraft. With these considerations, experiments on microorganisms were carried
      out in a vacuum chamber. For testing the effect of vacuum on the rate of
      desorption, mainly of water, measurement was made by a mass spectrometer. In the
      experiments the decompression rate was varied and different microbiological forms
      were used, namely, spores and vegetative cells of different cell wall structures.
      Further experiments in the ultrahigh-vacuum range are necessary and the problems
      involved are discussed.

PMID- 12197543
TI  - [A study on the size, location and medical function of the Jaedong Jejoongwon].
AB  - This is the study of Jaedong Jejoongwon, the first westernized hospital in Korea
      founded in 1885. To build the groundwork for study of Jejoongwon, its size,
      location, building structure, and medical functions were studied. At the same
      time, the history of Jejoongwon, particularly that of the time when there arose a
      need for its moving and expansion, was studied. Jaedong Jejoongwon was founded in
      a renovated building. The building was formerly owned by Hong Young-sik, who was
      killed while leading the Gapsinjungbyun. According to the existing block plan of
      Jaedong Jejoongwon, when it was opened in 1885, it was located in the place which
      later became a park. Nowadays this park is to northwest of the Constitutional
      Court. At that time, its size was about 600 p'yung. As the medical school was
      built, from end of 1885 to early 1886, Jejoongwon was expanded to north, and its
      size was enlarged to 862.16 p'yung. Jaedong Jejoongwon reflected the
      characteristics of western medical system. When it was opened in 1885, Jejoongwon
      consisted of a servants' room, an assistants' room, the outpatient clinic, the
      operation room (which was also used as the pharmacy), surgical wards, women's
      wards, and general wards. In 1886, as the number of patients was increased and
      medical school was opened, the function and the structure of hospital changed.
      The most significant change was that a new medical school building was built, as
      the nearby buildings were brought. The medical school consisted of the students'
      dormitory, a chemistry laboratory, and classrooms. Moreover, new functions were
      added to already-existed hospital building : a contagious ward, a waiting room
      for outpatients, an eye ward, a darkroom, a room for special diagnosis and
      treatment, and a vaccination room. Also, from the time when it was first opened,
      Jejoongwon needed the expansion, as too many patients came in and the medical
      education was started. Therefore, in the summer of 1886, Allen positively
      explored ways toward the hospital's moving. At last, in early 1887, Jaedong
      Jejoongwon moved to Kurigae on along with the development of medical education
      and medical treatment, shows how the modern medical system was formed and
      developed in Korea.

PMID- 12197544
TI  - [Development of National Institute of Health, Korea].
AB  - The National Institute of Health (NIH) under the Ministry of Health and Welfare
      of the Korean Government was established in 1963, integrating four institutes:
      National Institute of Health, National Chemical Laboratories, National Laboratory
      of Herb Medicine and National Institute of Public Health Training. The root,
      however, goes down to the Bacteriology Laboratory, opened in 1912 with the
      function for microbiological testing and pox vaccine development, which was
      absorbed into the former National Institute of Health in 1948 when the government
      of the Republic of Korea was inaugurated. The Institute opened a satellite
      office, the Masan Branch in 1977, and was further expanded, adding the Divisions
      of AIDS and Biotechnology in 1988. In 1996, as part of restructuring the
      Government organizations, Korea Food and Drug Administration (KFDA) ws founded by
      expanding the Toxicology Research Institute, to which all the functions of
      testing and certifying foods and drugs were transferred. Simultaneously, a new
      department, the Department of Biomedical science was organized, which currently
      consists of five divisions; the Divisions of Cancer Research, Degenerative
      Diseases, Cardiovascular Diseases, Metabolic Diseases and Genetic Diseases. In
      1999, in order to provide a rapid and effective disease control, the Department
      of Communicable Diseases was newly founded, merging the Division of Disease
      Control and Prevention from the Ministry of Health and Welfare. With these steady
      and significant changes, the NIH, together with the training of health manpower,
      has become the national organization for research, prevention and control of
      various diseases of public health importance in Korea.

PMID- 12197545
TI  - [The scenes of doctor-patient meeting in the contemporary Korean novels: chiefly
      on the basis of doctor's reading on patients].
AB  - "Medicine as an art" implies that there is something in medicine beyond the limit
      of science. The practice of medicine is far more than the simple application of
      scientific principles to a particular biologic aberration. The communication
      between a doctor and a patient is the core component of medical practice, but
      little attention has been generally drawn to it. This study shows three types of
      doctor's reading on 'patient' as an alternative model to see the doctor-patient
      communication on the basis of the concept of 'patient as a text' and Bakhtin's
      narrative theory. They are monologic, dialogic, and discontinuous readings. In
      monologic reading, the doctor has one - sidedly the whole power in communication
      and it reflects only the doctor's point of view. The doctor mainly concerns for
      the disease and its treatment. In the dialogic reading, the power of doctor
      patient is shared and their views are reflected each other The doctor should
      consider the patient as a human and understand his social and psychological
      surroundings. If the patient refuses to be treated, especially in the case of
      terminal cancer patient, he has nothing to do with his doctor. Therefore, the
      discontinuous reading can be applied and in result, no communication takes place
      between them. To evaluate the proposed types of the doctor's reading on patient,
      the three types can be applied to the scene of doctor-patient meeting in the
      novels. The meetings of lieutenant Sung and medical officers in Sending Back by
      Jung - In Suh are in accordance with the type of monologic reading. In Wan - Seo
      Park's Three Days in the Fall, the type of dialogic reading can be applied to
      that of the doctor I's lives with her patients. In Yong - Moon Chun's The Days of
      Dead Doctors, the type of discontinuous reading can be applied to the events
      between Haeng - Oh Kim and doctors in ICU. And the 3 parts of whose figure and
      relationship with Sorok Island have changed throughout the work. The doctors
      should have abundant experiences of life to make the dialogic reading possible.
      The dialogic reading can be realized, in its true sense, only if they see the
      patient not as a disease, but as a man and only if they make efforts to
      understand his circumstances.

PMID- 12197546
TI  - The Rx-to-OTC switch of Claritin, Allegra, and Zyrtec: an unprecedented FDA
      response to petitioners and the protection of public health.

PMID- 12197547
TI  - Heterotopic pregnancy at 16 weeks of gestation after in-vitro fertilization and
      embryo transfer.
AB  - We present an heterotopic pregnancy at 16 weeks of gestation following IVF/ET
      treatment with the ectopic pregnancy located in the left fallopian tube. Intra
      abdominal bleeding secondary to an heterotopic pregnancy, causing acute abdominal
      pain and hemorrhagic shock, should be included in the differential diagnosis even
      in the second trimester of pregnancy, especially in patients, achieving
      conception with the use of assisted reproduction techniques.

PMID- 12197548
TI  - Laparoscopic management of ovarian dermoid cysts. A series of 83 cases.
AB  - We did a retrospective survey of 83 patients who had laparoscopic removal of a
      benign dermoid cyst in our hospital since 1994. Preoperative transvaginal
      sonography led to the correct diagnosis in 57 cases (69%). In 59 cases cystectomy
      with ovarian conservation was performed; spillage of cyst contents occurred in 39
      cases (66%). Salpingo-oophorectomy was performed in 24 patients with spillage in
      8 cases (24%). The mean tumor size (n=83) was 4.5+/-1.6 cm and 4.9+/-2.8 cm for
      unspilled and spilled cysts, respectively. The tumor was placed in an endobag in
      62 cases. No intra- or postoperative complications occurred. No case of chemical
      peritonitis was noted.

PMID- 12197550
TI  - Normal nephrogenesis occurs in the early stage of bilateral multicystic
      dysplastic kidneys.
AB  - We present a case report about bilateral multicystic dysplastic kidneys (MCDKs).
      Pregnancy was terminated at 21 weeks' gestation and the fetus was examined by
      autopsy. The kidneys were replaced by many cysts and there was no parenchyma.
      However, on histological examination, there was normal nephrogenesis amid the
      cystic/dysplastic tissue. This suggests that normal nephrogenesis occurs before
      the secondary changes leading to MCDKs.

PMID- 12197549
TI  - The diagnostic challenge of peritoneal mesothelioma.
AB  - The differential diagnosis of diffuse malignant intraabdominal process in women
      may be a strenuous and long process. We report such a challenging, problematic
      case of peritoneal mesothelioma and present review of literature in search for
      best differentiating technique.

PMID- 12197551
TI  - Placental pathology in relation to the White's classification of diabetes
      mellitus.
AB  - The objective of this study was to investigate various macroscopic and
      microscopic features of the placenta in pregnancies complicated by diabetes
      according to White's classification. A total of 148 placentas were studied. Sixty
      five were from control patients and 83 from diabetic mothers. The diabetic
      mothers were further divided into three groups according to White's
      classification. There were 40 cases in White's group A and 36 cases in White's
      group B. There were 7 cases in White's groups C and D combined. Advanced maternal
      age and grandmultiparity were significantly higher in White A, White B and White
      C&D compared to the normal group. Mean weight of the mother was higher in White
      group A and group B compared to the control group and group C&D. The placental
      weight and neonatal weight were increased provided the diabetes was not
      complicated by vascular disease. With accompanying vascular disease the placental
      weight and neonatal weight were reduced compared to the controls. As a result of
      increased perinatal jeopardy the rate of operative delivery was higher in
      diabetic mothers. No major difference was observed in microscopic changes of
      placentas in different groups according to White's classification and the normal
      group.

PMID- 12197552
TI  - The effect of methyldopa treatment on uterine, umblical and fetal middle cerebral
      artery blood flows in preeclamptic patients.
AB  - The purpose of this study was to evaluate the efficacy of methyldopa in the
      treatment of preeclamptic patients. This study was performed on 24 preeclamptic
      women who were in between 25-36 weeks of gestational age. 24 healthy pregnant
      women were taken as control group. Before starting treatment, 24 preeclamptic
      patients were examined with Doppler ultrasound. Pulsatility index, resistance
      index, systolic/diastolic ratio of uterine, umblical and fetal middle cerebral
      arteries were measured. Preeclamptic patients were treated with totally 1 g
      methyldopa per day. After 7 d, patients were reexamined with Doppler ultrasound.
      The effect of methyldopa on uterine, umblical and fetal middle cerebral artery
      blood flows were detected. Only one control with Doppler ultrasound was done to
      the healthy pregnant women. Before methyldopa treatment to the preeclamptic
      women, pulsatility index (PI), resistance index (RI) and systolic/diastolic ratio
      (S/D) on uterine and umblical arteries were significantly higher than the control
      group. However, fetal middle cerebral artery (MCA) values were significantly
      lower than the control group. When Doppler results of preeclamptic patients
      before and after the methyldopa treatment were compared, no significant
      differences in terms of Pulsatility Index, Resistance IndexI and S/D ratio of
      umblical and fetal middle cerebral arteries were found. However, the results of
      uterine artery were significantly lower after the treatment in preeclamptic
      patients. Treatment with methyldopa lowered the uterine artery resistance in
      preeclamptic patients but did not effect the resistance of umblical and fetal
      middle cerebral artery.

PMID- 12197553
TI  - Changes of the electrical heart field and hemodynamic parameters in the 34th to
      40th weeks of pregnancy and after delivery.
AB  - We have studied changes of the electrical heart field resulting from the changed
      spatial position of the heart during the last period of pregnancy in healthy
      women. This was suggested to be a good model of electrocardiographic changes that
      could be found on patients suffering from obesity. The measured parameters of the
      electrical heart field were compared with hemodynamic parameters before and after
      delivery in the group of non-obese women with physiological pregnancy and in a
      group of healthy non-obese and non-pregnant women. Several significant changes of
      the electrical heart field were detected in the late pregnancy: increased heart
      rate, shortening of A-V conductance, prolongation of QT interval normalised for
      the heart rate and changes in the ventricular depolarisation and repolarisation
      patterns. Some of these changes are not fully restored in 4 days after delivery.
      Moreover, we have found an increased pump function of the left ventricle
      accompanied by decreased peripheral resistance in the group of pregnant women.
      Increased pump function was partially restored after delivery, peripheral
      resistance was not only restored, but it overshot to increased values. Persisting
      elevated heart rate with increased peripheral resistance suggested increased
      sympathetic activity after birth. Only some changes of electrical heart field
      could be explained by changed spatial arrangement of the chest organs during
      pregnancy and they must be considered in a complex consequence with changes in
      regulatory mechanisms.

PMID- 12197554
TI  - Comparison of dexa and ultrasonometry in the measurement of bone density.
AB  - The aim of our study was to evaluate the diagnostic agreement between
      quantitative sonography of the calcaneum (QUS) and dual energy X-ray
      absorptiometry (DEXA) of the spine and femur. 153 women enrolled in our study and
      were divided in three groups. Group A was composed of women aged between 45 and
      55, Group B of women of 56-66 and Group C of women 67-77. Mean height cm 164+/
      2.8; mean weight kg 68+/-3.2. The most concordant results were obtained in group
      B. This suggests that QUS screening for osteoporosis may be suitable for the
      "younger" perimenopausal patient.

PMID- 12197555
TI  - Increased frequency of abnormal Papanicolaou smears in adolescents.
AB  - Abnormal Papanicolaou smears has increased in adolescents. Our objective was to
      analyze the frequency of cervical intraepithelial neoplasia (CIN) in adolescents
      (< 20 years of age) over the last 12 years, comparing to adult (> or = 20 years
      of age). We studied 110,283 (10.85% of adolescents) reports from Papanicolaou
      smears between 1987 and 1999 in a public university hospital that has a screening
      program for cervical cancer prevention. The tests were divided into 3 periods
      (1987-1991, 1992-1995 and 1996-1999) for studying the evolution of frequencies.
      CIN I was more frequent among adolescents (1.73% vs. 0.99%) and CIN III and
      invasive cancer among adult women (0.62% vs. 0.05%, and 0.39% vs. 0.0083%,
      respectively). Between the periods 1987-1991 and 1996-1999 there was an increased
      in the frequency of CIN I among adolescents (from 0.78-2.17%) and adults (from
      0.72-1.16%); CIN II decreased among adult patients (from 0.52-0.28%) and tripled
      among adolescents over recent years (from 0.15-0.47%), and CIN III increased in
      both group, although without statistical significance. One case of invasive
      carcinoma among adolescents occurred in the period from 1996-1999. We strongly
      recommend the inclusion of adolescent populations in the screening programs, from
      the time that they begin sexual activity.

PMID- 12197556
TI  - A study of hysteroscopic metroplasty in 141 women with a septate uterus.
AB  - 141 patients who had a hysteroscopic septum resection of a partial uterine septum
      (class Vb, American Society for Reproductive Medicine, ASRM) were divided into
      two groups: Group I (69 patients) presented with infertility and Group II (72
      patients) with recurrent abortion. The mean+/-SD post-operative follow up period
      was 36+/-19.5 months. Thiry-six Group I patients (52.1%) and 38 Group II patients
      (52.7%) achieved pregnancy, with respective abortion rates of 20% and 25%.

PMID- 12197557
TI  - Postpartum bleeding and von Willebrand's disease.
AB  - We calculated the decreases in hemoglobin levels between the day of delivery and
      postpartum day 3 in all 3565 deliveries of the year 1997. Fourteen patients had a
      drop in hemoglobin level of more than 8% and were included in the study. Ten
      women without excessive bleeding served as a control group. In all women tested,
      plasma von willebrand factor antigen (vWF:Ag) correlated well with factor VIII:C
      activity, and both were within normal limits, so that we were able to exclude the
      presence of type I von willebrand's disease (vWD I). Two women in the excessive
      bleeding group were found to have an isolated decrease in coagulation factor
      activity. In one patient, factor XI:C and XII:C activities were reduced to 46%
      and 53% respectively, and APTT was prolonged to 48.5 seconds. In the other,
      factor VII:C activity had dropped to 69%, and Normotest results were only 62%.
      Ten of the 14 patients and 1 woman of the control group were diagnosed as having
      mild anemia. We conclude that investigations for vWD I should only be done in
      women with a previous history of abnormal bleeding.

PMID- 12197558
TI  - Malformations in newborn: results based on 30,940 infants and fetuses from the
      Mainz congenital birth defect monitoring system (1990-1998).
AB  - Prevalence rates of birth defects in the Federal Republic of Germany are
      informative to assess the general background risk of having a child with a birth
      defect. They provide basic figures to determine temporal and regional prevalence
      trends, to evaluate and initiate preventive measures and to initiate research
      projects. To avoid observer, definition and collection bias, active monitoring
      systems are required. Data collected in the active monitoring system of the Mainz
      Birth Defects Registry are presented. From 1990-1998, 30,940 live-births,
      stillbirths and abortions underwent standardized physical and sonographic
      examinations. Anamnestic data were collected from prenatal care records,
      maternity files and hospital records. Major malformations were diagnosed in 2144
      (6.9%) and mild errors of morphogenesis in 11,104 (35.8%) of all infants. Risk
      factors associated with the occurrence of major malformations were identified by
      comparing anamnestic data from infants with and without major malformations.
      Using multivariate regression models, statistically significant associations were
      established for 9 risk factors. Causally related risk factors were parents or
      siblings with malformations, parental consanguinity, more than 3 minor errors of
      morphogenesis in the proband, maternal diabetes mellitus and ingestion of
      antiallergic drugs in the first trimester of pregnancy. Conjunctional risk
      factors were polyhydramnios, oligohydramnios and gestational age <32 weeks at
      birth. Using these risk factors, populations at risk for the occurrence of major
      malformation can be identified.

PMID- 12197559
TI  - Identification of Chlamydia trachomatis DNA in human papillomavirus (HPV)
      positive women with normal and abnormal cytology.
AB  - Insofar as infection with human papillomavirus (HPV) and Chlamydia trachomatis
      (CT) are associated with cervical intraepithelial neoplasia (CIN), the aim of
      this study was to assess the correlation of HPV and CT infection in patients with
      normal or abnormal cytology. Endocervical samples from patients (n=121; mean age
      33.7+7.0) were assessed for HPV and CT DNA by PCR. While there was no
      statistically significant difference between HPV-positive (n=44) and HPV-negative
      (n=77) patients to age pregnancies, higher proportion of smokers, patients with
      multiple male sex partners, or with abnormal cytology was seen in HPV-positive
      vs. HPV-negative women, respectively. An infection rate of CT of 21/44 was seen
      in HPV-positive as compared to 11/77 in HPV-negative patients. Within HPV
      positive patients, there was no significant difference between CT-positive and CT
      negative patients with regards to the risk factors studied. Collectively, this
      suggests that a causal relationship between HPV and CT infection in the
      development of CIN disease.

PMID- 12197560
TI  - Clear cells carcinoma of fallopian tubes associated with tubal endometriosis.
      Case report and review.
AB  - Our case report describes a patient with clear cell fallopian tube carcinoma
      (histological grade 3; stage (FIGO): III c.) associated with an endometrial cyst
      of the tube wall.

PMID- 12197561
TI  - Parathyroid agenesis: prenatal ultrasonographic features and pathological
      findings.
AB  - We report a girl with parathyroid agenesis. The gross anomaly of the long bones
      was diagnosed prenatally by ultrasound. Pregnancy was terminated at 24 weeks of
      gestation. There were no other apparent system anomalies except parathyroid gland
      agenesis and long bone abnormalities. This case is the first reported case of
      parathyroid agenesis with normal thyroid glands and other systems.

PMID- 12197562
TI  - Small cell carcinoma of the endometrium with concomitant pelvic inflammatory
      disease.
AB  - BACKGROUND: Small cell carcinoma of the endometrium is a rare disease entity
      characterized by bulkiness and predisposition to necrosis. Clinical presentations
      include postmenopausal bleeding, lower abdominal mass, chronic abdominal pain and
      menorrhagia. We present a case of small cell carcinoma of the endometrium with
      concomitant pelvic inflammatory disease. The literature is also reviewed. CASE: A
      64 year old female presented was admitted with the principal complaints of fever,
      lower abdominal pain and malodorous vaginal discharge. Bimanual examination
      revealed cervical motion tenderness with a WBC of 9400 cells/microL and increased
      levels of neutrophils, band cells and C-reactive protein. Sonography revealed an
      adnexal echocomplex compatible with tubo-ovarian abscess. Culture of the vaginal
      discharge revealed the presence of E. coli. Symptoms persisted despite three days
      of antibiotics administration so a laparotomy was performed with a friable
      hemorrhagic uterus revealed and an area of necrosis evident in the left adnexa.
      Malignancy was confirmed from frozen section. Total abdominal hysterectomy, with
      bilateral salpingooophorectomy and optimal debulking, was performed. The final
      pathology report confirmed small cell carcinoma of the endometrium. CONCLUSION:
      Malignancy and pelvic inflammatory disease have overlapping clinical
      characteristics. Once pelvic inflammatory disease is suspected in a
      postmenopausal patient, malignancy should also be suspected, and a thorough
      examination and a tumor-marker analysis performed.

PMID- 12197564
TI  - Professionalism: reviving or redrawing the social contract?

PMID- 12197563
TI  - Uncomplicated pregnancy and normal singleton delivery after surgical excision of
      heterotopic (cornual) pregnancy following in vitro fertilization/embryo transfer.
AB  - A 39 year-old woman with previous salpingectomy developed a symptomatic
      heterotopic right cornual pregnancy identified by transvaginal ultrasonography at
      six weeks' gestation. The patient had previously undergone an ipsilateral partial
      salpingectomy, and the conception was established four months later after one
      cycle of controlled ovarian hyperstimulation, in vitro fertilization (IVF) and
      embryo transfer. We performed immediate surgical excision of the ectopic
      implantation with conservation of the intrauterine pregnancy. Progesterone was
      administered as 200 mg/d lozenge (troche) plus 200 mg/d rectal suppository,
      maintained from day of embryo transfer through the perioperative period and until
      11th gestational week. Following an uneventful obstetrical course, a healthy male
      infant was delivered by cesarean at term. In this report, we review the incidence
      and significance of heterotopic gestation in the context of IVF/embryo transfer.
      Risk factors for complex intra- and extra-uterine pregnancies are also outlined.
      Additionally, the clinical management of heterotopic pregnancy, including a novel
      approach to progesterone supplementation, is discussed.

PMID- 12197565
TI  - Anti-IgE in the real world.

PMID- 12197566
TI  - Distal lung inflammation in asthma.
AB  - OBJECTIVE: To review the role of distal lung inflammation in asthma. DATA SOURCES
      AND STUDY SELECTION: Selected peer-reviewed research publications retrieved from
      MEDLINE search. Search was restricted to English-language publications only.
      Included articles were selected for their relevance to pathophysiology,
      diagnosis, and treatment. Bibliographies of selected papers served as an
      additional source of considered publications. RESULTS: Inflammation in the small
      airways and alveolar tissue plays an important role in the clinical
      manifestations of asthma. Diagnostic modalities such as transbronchial biopsy and
      evolving radiologic techniques such as high-resolution computed tomography are
      improving our ability to evaluate this portion of the lung. New ultra-fine
      particle size metered-dose inhalers and oral agents such as cysteinyl leukotriene
      receptor antagonists offer new opportunities for treating small airways
      inflammation and need to be fully evaluated for their ability to target and treat
      distal lung inflammation. CONCLUSIONS: Distal lung inflammation is an important
      component of airway inflammation in asthma. New modalities for evaluating distal
      airway inflammation and for targeting the distal lung with inhaled and systemic
      drugs are rapidly expanding our knowledge of the clinical importance of distal
      lung inflammation and may ultimately be of critical importance in asthma therapy.

PMID- 12197567
TI  - Refractory atopic dermatitis treated with low dose cyclosporin.

PMID- 12197568
TI  - Omalizumab and the immune system: an overview of preclinical and clinical data.
AB  - OBJECTIVE: This review discusses the role of immunoglobulin (Ig)E in allergic
      disease, inhibition of IgE with omalizumab, and the consequences of IgE
      inhibition (both clinically and in terms of the effect on the immune system).
      DATA SOURCES: Relevant publications obtained from a literature review. STUDY
      SELECTION: Relevant publications on IgE, allergic disease, and anti-IgE were
      critically evaluated. RESULTS: IgE plays a key role in allergic diseases such as
      allergic asthma and allergic rhinitis. Its role in healthy individuals is less
      well defined. Treatment of allergic asthma and rhinitis with omalizumab, a
      humanized monoclonal anti-IgE antibody, causes a marked reduction in circulating
      free IgE levels. This has been shown to reduce symptoms and decrease the need for
      other medication in patients with these allergic diseases. Anti-IgE treatment
      with omalizumab did not cause any of the complications that might, in theory, be
      expected to result from reduction in circulating free IgE, such as adverse
      effects upon the immune system or other body systems. CONCLUSIONS: The limited
      clinical data currently available suggest that this novel method of treatment for
      allergic asthma and rhinitis seems to be both effective and well tolerated in
      clinical use.

PMID- 12197569
TI  - Impact of respiratory symptoms on health-related quality of life and medical
      resource utilization of patients treated by allergy specialists and primary care
      providers.
AB  - BACKGROUND: Respiratory symptoms associated with allergy and asthma cause
      substantial health care burden. OBJECTIVE: This observational pilot study
      compared internal medicine/family practice (IM/FP) and pediatric primary care
      providers with allergists in the diagnosis, treatment, and health-related quality
      of life (HRQL) outcomes of adults and children with respiratory symptoms.
      METHODS: Two allergists, 2 IM/FP, and 2 pediatricians enrolled 242 patients with
      respiratory symptoms ages 5 to 16 years old (n = 123) and 17 to 70 years old (n =
      119). HRQL questionnaires were completed at enrollment and quarterly for 1 year.
      The adult questionnaire included SF-36, respiratory symptom role productivity,
      ITG Asthma Short Form, and allergy symptom index (ASI) scales. The child
      questionnaire included CHQ-PF28, respiratory symptom family impact, ITG Child
      Asthma Short Form, and ASI scales. HRQL changes were evaluated over the study
      period. RESULTS: Adults treated by allergists reported significantly greater
      improvement in HRQL on 5 of 8 SF-36 scales, the respiratory symptom role
      productivity scale, 3 of 5 ITG Asthma Short Form scales, and 2 of 4 ASI scales
      compared with adults treated by an IM/FP (P < 0.05). Pediatric patients treated
      by allergists had significantly greater improvement on 3 of 15 CHQ-PF28 scales,
      the respiratory symptom family impact scale, and one ASI scale compared with
      patients treated by pediatricians (P < 0.05). CONCLUSIONS: Compared with patients
      treated by primary care physicians, patients treated by allergists reported
      greater improvement in HRQL in a number of scales. Additional research is
      required to further evaluate the impact of provider specialty and patterns of
      care on outcomes of respiratory symptoms patients.

PMID- 12197570
TI  - Factors associated with asthma in young Danish adults.
AB  - BACKGROUND: The prevalence of asthma appears to be increasing, but our knowledge
      about factors associated with asthma in young adults is limited. Factors
      associated with asthma were studied in 624 (66% of those invited) young Danish
      adults (aged 19 to 29 years). OBJECTIVE: The purpose of this study was to
      investigate the prevalence and predictors of asthma in young Danish adults.
      METHODS: Case history, including respiratory symptoms, smoking habits, education,
      and employment, was obtained by interview, and a questionnaire and was used to
      evaluate the presence or absence of asthma. Pulmonary function, beta2
      reversibility, airway responsiveness to histamine, and blood eosinophil count
      were measured using standard techniques. RESULTS: The lifetime prevalence of
      asthma in these young Danish adults was 17%, and the prevalence of current asthma
      was 9%. The proportion of current smokers was disturbingly high, 41%, and,
      further, the proportion of current smokers was significantly higher among those
      with asthma than among those without asthma (52% and 38%, respectively; P <
      0.01). Asthma was significantly associated with current smoking, with lower than
      predicted forced expiratory volume in 1 second, with lower than predicted ratio
      of forced expiratory volume in 1 second/forced vital capacity, atopy, higher
      eosinophil count, and higher degree of airway responsiveness to histamine. The
      proportion of subjects with no education after junior high school was higher
      among those with asthma than among those without asthma (P < 0.05). Further, 16
      of the 103 (16%) people with asthma had work-related worsening of their
      respiratory symptoms. CONCLUSIONS: The presence of current asthma was predicted
      by current smoking, lower level of lung function, less education, higher blood
      eosinophil count, and more pronounced airway responsiveness. Further, the
      proportion of current smokers was higher among asthmatic subjects than among
      nonasthmatic subjects. Greater efforts must be made to encourage young people
      with asthma not to smoke.

PMID- 12197571
TI  - Possible association between cockroach allergy and HLA class II antigens.
AB  - BACKGROUND: Susceptibility to the development of allergic diseases is known to be
      associated with genetic components, as well as environmental factors. Although
      the genetics of immunoglobulin E, atopy, and asthma are complex, genetic markers
      are needed to identify populations at risk and to plan intervention studies.
      OBJECTIVE: Human leukocyte antigen (HLA) class II genes play a major role in the
      control of immune response. We investigated the association between HLA class II
      alleles of DRB1 and DQB1 and the expression of atopy in cockroach-sensitive
      patients. METHODS: Levels of total and specific immunoglobulin E were determined.
      Skin prick tests were performed. HLA class II typing was performed by the
      Polymerase chain reaction with sequence-specific primers. Distribution of the HLA
      genotypes of 32 cockroach-positive atopic patients from the inner city were
      compared with those of 32 healthy, nonatopic controls of Turkish Caucasian
      origin. RESULTS: HLA class II gene analysis showed an increase of the HLA
      DRB1*0701 and HLA-DQB1*02 alleles in atopic patients compared with nonatopic
      controls (31.3% vs 3.1% and 50% vs 15.6%, Pc < 0.036 and Pc < 0.021,
      respectively). Conversely, HLA-DRB1*15 allele was encountered more frequently in
      the control subjects. An association between cockroach sensitivity and cutaneous
      reactivity to other aeroallergens was observed (P < 0.001). CONCLUSIONS: It is
      suggested that the higher frequencies of HLA-DRB1*0701 and HLA-DQB1*02 alleles
      are probably related to atopy rather than an association between class II
      antigens and cockroach allergy in this group of polysensitized, atopic
      individuals. Further studies may lead to a better understanding of the
      genetically determined susceptibility, and evaluate the individual effects of
      each locus (or allele) on sensitivity to specific allergens in the Turkish
      population.

PMID- 12197572
TI  - Establishing a model of seasonal allergic rhinitis and demonstrating dose
      response to a topical glucocorticosteroid.
AB  - BACKGROUND: Symptoms of seasonal allergic rhinitis may vary greatly. Hence, for
      research purposes, there is a need for disease-like models of allergic rhinitis.
      In a preliminary study, involving 7 days' challenge with allergen, promising
      symptom consistency was obtained and dose-response to a glucocorticosteroid
      could, in part, be demonstrated. OBJECTIVE: To establish this model of seasonal
      allergic rhinitis and test the hypothesis that mometasone furoate is more potent
      than budesonide as an antirhinitis drug. METHODS: Thirty-eight patients with
      seasonal allergic rhinitis received treatment with spray-formulations of placebo,
      budesonide 64 microg, budesonide 256 microg, and mometasone furoate 200 microg in
      a double-blind, crossover design. After 3 days' treatment, individualized nasal
      allergen-challenges were administered daily for 7 days while the treatment
      continued. Nasal symptoms and peak inspiratory flow (PIF) were recorded. RESULTS:
      During the last 3 days of allergen challenge without active treatment, consistent
      around-the-clock symptoms were recorded and recordings during these days were
      used in the analysis. With few exceptions the active treatments reduced nasal
      symptoms and improved nasal PIF (P values <0.001 to 0.05). Budesonide caused dose
      dependent improvements in evening symptoms, morning nasal PIF, and nasal PIF
      recorded 10 minutes after allergen-challenge (P values <0.05). Budesonide 256
      microg produced greater improvement than mometasone furoate 200 microg for nasal
      PIF 10 minutes after allergen-challenge (P < 0.05). CONCLUSION: The present
      allergen challenge method, producing consistent symptoms and nasal PIF data,
      emerges as a model of seasonal allergic rhinitis well suited for exploring
      potency and efficacy of drug intervention. The present data do not support the
      view that mometasone furoate is a more potent antirhinitis drug than budesonide.

PMID- 12197573
TI  - Clinical characteristics of patients with mustard hypersensitivity.
AB  - BACKGROUND: Although mustard is frequently consumed in Spain and elsewhere, only
      isolated case reports of mustard allergy have been reported. No large series of
      case studies have been published. OBJECTIVES: We sought to describe demographic,
      clinical, and immunologic characteristics of patients with mustard
      hypersensitivity and to determine whether any significant differences exist in
      age, sex, atopic family history, total immunoglobulin E (IgE) level, and specific
      IgE to mustard ratio among patients with differing characteristics. METHODS:
      Twenty-nine patients with a history of mustard allergy underwent skin prick tests
      with mustard, determination of total IgE, and evaluation of specific IgE to
      mustard. Skin prick tests with Lolium perenne, Olea europaea, and Artemisia
      vulgaris were done in patients with symptoms of pollinosis. The aforementioned
      variables were compared between various subgroups of patients for systemic versus
      local reactions to mustard, association versus no association with allergies to
      other vegetable foods, and association versus no association with pollinosis.
      RESULTS: The male:female ratio was 10:19. Skin prick tests to mustard were
      positive in all patients. The total IgE geometric mean was 189.3 kU/L. The
      specific IgE to mustard was positive in all patients (0.7 to > 100 kU/L). Of the
      29 patients, 19 (66%) had a systemic reaction after consumption of mustard, and
      10 (34%) had a local reaction; 14 (48%) had anaphylaxis. Fifteen patients (52%)
      had symptoms after ingestion of other vegetable foods, and 15 also had typical
      symptoms of pollinosis. No significant differences were found in age, sex, atopic
      family history, total IgE, and specific IgE to mustard between the various
      subgroups studied. CONCLUSIONS: Most study patients with mustard hypersensitivity
      had a systemic reaction and had associated pollinosis or allergy to other
      vegetable foods. Mustard sensitivity should be routinely tested in patients with
      idiopathic anaphylaxis.

PMID- 12197574
TI  - Effect of minocycline and doxycycline on IgE responses.
AB  - BACKGROUND: We have recently found that the tetracycline minocycline suppresses
      inflammatory responses in serum immunoglobulin (Ig)E-positive asthmatic patients,
      and that IgE levels can decrease in these patients. The mechanism by which
      minocycline suppresses these responses is unknown. OBJECTIVE: We have now
      investigated the ability of the tetracyclines, minocycline and doxycycline, to
      regulate IgE responses of peripheral blood mononuclear cells (PBMC) obtained from
      serum IgE-positive asthmatic patients. METHODS: The distributions of CD3+, CD4+,
      CD8+, and CD19+ lymphocytes in peripheral blood of serum IgE-positive asthmatic
      patients and IgE-negative nonasthmatic controls, and cytokine-specific mRNA
      expression by their PBMC were determined by flow cytometry (reverse transcriptase
      polymerase chain reaction). Serum Ig levels also were determined (nephelometry,
      fluoroenzymeimmunoassay, enzyme-linked immunoadsorbent assay; n = 7/group). PBMC
      (1.5 x 10(6)/mL) were cultured with anti-CD40 monoclonal antibody and recombinant
      human interleukin-4 in the presence/absence of minocycline or doxycycline (0.1 to
      10 microg/mL), and IgE levels in supernatants determined on days 0, 3, and 10
      (enzyme-linked immunoadsorbent assay). RESULTS: Asthmatic and nonasthmatic
      subjects had similar numbers of blood CD4+ T cells (779/mm3 +/- 73 and 766 +/-
      115, respectively) and CD19+ B-cells (239/mm3 +/- 35 and 379 +/- 95,
      respectively); however, CD8+ T cell numbers were decreased in asthmatic compared
      with nonasthmatic subjects (378/mm3 +/- 66 and 568 +/- 53, respectively; P =
      0.045). High IgE levels were detected in supernatants of asthmatic PBMC on day 10
      (28 ng/mL +/- 12), whereas control IgE levels did not change (<2.5 ng/mL). When
      either minocycline or doxycycline was included in culture, IgE production by
      asthmatic PBMC was strongly suppressed in dose-dependent fashion on day 10 (>80%
      with 10 microg/mL); control IgE did not change (<2.5 ng/mL). CONCLUSIONS: The
      results are consistent with the idea that the therapeutic benefits obtained by
      asthmatic patients from minocycline may, in part, result from IgE suppression.

PMID- 12197576
TI  - Mortality from asthma in children and young adults in Louisiana.
AB  - BACKGROUND: Asthma mortality rates have been increasing despite our improved
      understanding of the pathophysiology of asthma and advanced methods of treatment.
      Although there are many national studies of asthma mortality rates, few studies
      have concentrated on subnational regions such as individual states. OBJECTIVES:
      We sought to determine the trends in asthma mortality in children and young
      adults during the last 15 years in Louisiana. METHODS: Asthma mortality data were
      acquired from the Louisiana State Center for Health Statistics for the years 1983
      through 1997. All asthma deaths coded International Classification of Disease,
      Ninth Revision 493 were included in the data set along with year, sex, and rate
      characteristics. State population estimates obtained from the United States
      Bureau of Census for three 5-year periods (1983 to 1987, 1988 to 1992, and 1993
      to 1997) were used to calculate crude and adjusted mortality rates. These time
      periods were compared with one another and with the period 1983 to 1987, which
      was used as a baseline. RESULTS: For all residents, the mortality rate increased
      from 0.41 deaths per 100,000 persons during the 1983 to 1987 time period to 0.49
      and 0.63 deaths per 100,000 persons during 1988 to 1992 and 1993 to 1997 time
      periods, respectively. Mortality rates have increased in both the white and non
      white populations over the 15-year study period, with the most pronounced
      increases among the non-white population. CONCLUSION: Asthma mortality rates in
      Louisiana have increased, particularly among the non-white population, over the
      last 15 years, although the results are not statistically significant. When
      compared with other states, asthma mortality in Louisiana is lower than in the
      northeast and central north states.

PMID- 12197577
TI  - Chronic idiopathic urticaria: a family study.
AB  - BACKGROUND: Genetic factors play a pivotal role in the pathogenesis of many
      autoimmune disorders. Recent studies demonstrated that chronic idiopathic
      urticaria (CIU) is an autoimmune disease at least in a subset of patients, but
      familial studies have not yet been conducted. OBJECTIVE: To investigate the
      familial pattern of CIU. METHODS: One thousand three hundred eight adults with
      CIU (aged >12 years; male/female 388/920) seen during the last 10 years were
      thoroughly interviewed to ascertain the presence of CIU among first-degree
      relatives. Positive histories were confirmed by medical recordings. Proportions
      were compared with those expected in the general population on the basis of a
      0.1% prevalence of the disease. RESULTS: Fifty-six of 1,308 (4%) patients had a
      familial history of CIU affecting at least one first-degree relative. This number
      exceeded by approximately eight times the expected one (P < 0.001). Twenty-two of
      23 (96%) patients with a positive familial history were positive on autologous
      serum skin test (P < 0.01 by comparison with previous studies). CONCLUSION: The
      observation that CIU is much more frequent among first-degree relatives of
      affected individuals than in the general population suggests the existence of a
      genetic background for the disease and provides a clinical support to the
      reported association between CIU and human leukocyte antigen DR4. Ninety-six
      percent of patients with a positive familial history were positive on autologous
      serum skin test, a condition that has been associated with the presence of
      circulating histamine releasing factors, including anti-Fc epsilonRI or anti
      immunoglobulin E antibodies.

PMID- 12197575
TI  - One-year efficacy and safety of inhaled formoterol dry powder in children with
      persistent asthma.
AB  - BACKGROUND: The long-term efficacy and safety of formoterol dry powder capsules
      for inhalation in pediatric asthma have not previously been evaluated. OBJECTIVE:
      We examined the effectiveness of inhaled formoterol over a period of 12 months in
      asthmatic children who were still symptomatic despite anti-inflammatory
      treatment. METHODS: After a run-in period, 518 patients (5 to 12 years old) were
      randomized in a double-blind manner to receive 12 or 24 microg formoterol dry
      powder (Foradil, Novartis Pharma AG, Basel, Switzerland) or placebo twice daily
      for 12 months. The drug was administered by inhaler (Aerolizer, Novartis Pharma
      AG) and was given in addition to their anti-inflammatory treatment. The primary
      variable was the area under the curve for forced expiratory volume in 1 second
      measured over 12 hours after the morning dose of study medication. RESULTS: The
      area under the curve for forced expiratory volume in 1 second after the first
      dose of treatment and after 3 and 12 months of treatment was significantly
      greater for patients receiving formoterol 12 microg and 24 microg than for
      patients receiving placebo (all P < or = 0.0062). Compared with placebo, both
      doses of formoterol significantly improved morning and evening premedication peak
      expiratory flow rate (all P < 0.001). In the group treated with formoterol 24
      microg, median symptom score and median dose of rescue medication at night were
      lower than during the run-in period, whereas the opposite occurred in the placebo
      group. The incidence of hospitalizations for asthma was higher in the formoterol
      groups than in the placebo group. CONCLUSION: Our results indicate that, in
      asthmatic children who are still symptomatic despite anti-inflammatory therapy,
      the addition of formoterol consistently improves airflow obstruction and
      nocturnal symptoms and reduces the use of rescue medication. However, this
      treatment requires close disease monitoring to detect early signs of acute
      exacerbation.

PMID- 12197578
TI  - Glucoamylase: another fungal enzyme associated with baker's asthma.
AB  - BACKGROUND: Aspergillus-derived enzymes are widely used as dough additives in the
      baking industry. These enzymes may give rise to immunoglobulin (Ig)E-mediated
      sensitization and occupational asthma. Glucoamylase (or amyloglucosidase) is an
      important industrial enzyme obtained from Aspergillus niger and used to provide
      fermentable sugars for yeast to improve loaf volume and texture. OBJECTIVE: The
      aim of our study was to investigate the potential allergenic role of glucoamylase
      in baker's asthma. METHODS: We report four subjects with work-related allergic
      respiratory symptoms who were exposed to glucoamylase and other starch-cleaving
      enzymes used as baking additives. The causative role of glucoamylase in work
      related asthma was investigated by immunologic tests and specific inhalation
      challenges (SIC). Glucoamylase allergenic components were characterized by sodium
      dodecyl sulfate-polyacrylamide gel electrophoresis and immunoblotting. RESULTS:
      Skin prick tests to glucoamylase (10 mg/mL) gave a positive response in all
      patients. Further, a positive skin prick test to alpha-amylase was obtained in
      the four patients and to hemicellulase in two of them. SIC to glucoamylase
      elicited isolated early asthmatic responses in the three patients tested, and SIC
      to alpha-amylase elicited early asthmatic responses in two patients and a dual
      asthmatic response in another patient. Immunoblotting with glucoamylase showed
      several IgE-binding bands with molecular masses between 33 and 96 kD. IgE
      inhibition assays showed scarce to moderate allergenic cross-reactivity between
      glucoamylase and alpha-amylase. CONCLUSIONS: These bakers had developed IgE
      mediated occupational asthma to glucoamylase and alpha-amylase. Fungal
      glucoamylase is widely used as a baking additive and this enzyme may give rise to
      allergic respiratory reactions among exposed workers.

PMID- 12197579
TI  - Sensitization to recombinant Aspergillus fumigatus allergens in allergic fungal
      sinusitis.
AB  - BACKGROUND: Allergic bronchopulmonary mycosis is primarily caused by Aspergillus
      fumigatus. Despite similarities, allergic fungal sinusitis (AFS) is thought to be
      caused by various fungi. OBJECTIVE: Identify fungal elements in AFS allergic
      mucin and determine the prevalence of specific immunoglobulin (Ig)E to
      recombinant A. fumigatus allergens (rAsp) in AFS patients. METHODS: Allergic
      mucin from 17 definitive and 10 probable AFS patients were histologically
      examined for fungal elements. Sera from 18 definitive AFS patients, 10 probable
      AFS patients, 6 chronic sinusitis patients, and 5 A. fumigatus-allergic patients
      were tested for specific IgE to A. fumigatus and five rAsps. RESULTS: Ten of the
      17 definitive cases had hyphae morphologically resembling Aspergillus or Fusarium
      spp. One probable AFS patient had similar findings. Of definitive patients, 94%
      (17 of 18) showed A. fumigatus-specific IgE (> or = 0.35 kUa/L), and 67% were
      positive to one or more rAsp. Four of 10 probable patients demonstrated A.
      fumigatus-specific IgE, and 2 had IgE to one or more rAsp. The definitive group
      had greater mean A. fumigatus IgE (P < 0.05) versus the probable and chronic
      sinusitis groups. The definitive group's rate of IgE to the rAsps was
      statistically greater. All definitive patients with Aspergillus or Fusarium spp.
      in situ had A. fumigatus-specific IgE, and 7 of 10 had IgE to at least one rAsp.
      CONCLUSIONS: Most definitive AFS patients have A. fumigatus-specific IgE and many
      have specific IgE to rAsps. Many also demonstrate Aspergillus spp. or Fusarium
      spp. in situ. Findings suggests that A. fumigatus is an important causative agent
      in AFS in the southeast United States.

PMID- 12197580
TI  - Atrial fibrillation associated with anaphylaxis during venom and pollen
      immunotherapy.
AB  - BACKGROUND: Electrographic changes after insect stings have been reported both
      with and without systemic symptoms. To our knowledge, however, there have been no
      reported cases of arrhythmias in the maintenance phase of venom or pollen
      immunotherapy. OBJECTIVE: We report a case of a patient who developed paroxysmal
      atrial fibrillation after receiving venom and pollen immunotherapy. This patient
      was initially evaluated in an outpatient setting, and the events described
      occurred at an allergist's private office. We believe this is an atypical
      presentation and would be very pertinent to the practicing allergist. METHODS:
      This patient was under the care of a clinical allergist in a private practice
      with associations to a teaching hospital. Interventions were as described in the
      body of the paper, more specifically venom and pollen maintenance immunotherapy
      followed by two doses of 0.3 mL of 1:1,000 concentration epinephrine
      intramuscularly. RESULTS: Patient was found to be in atrial fibrillation along
      with systemic symptoms immediately after administration of immunotherapy. After
      epinephrine administration, patient converted back to normal sinus rhythm and
      systemic symptoms resolved. CONCLUSIONS: Atrial fibrillation is an atypical
      presentation of a systemic reaction to immunotherapy.

PMID- 12197581
TI  - Successful treatment of autoimmune chronic idiopathic urticaria with intravenous
      cyclophosphamide.
AB  - BACKGROUND: A 45-year-old woman presented with a 20-year history of chronic
      idiopathic urticaria (CIU) unresponsive to H1- and H2-antagonists and
      combinations of other anti-inflammatory agents but controlled with daily
      prednisone (35 mg) for more than 13 years. Intracutaneous testing to autologous
      serum revealed an 8 x 10-mm wheal/flare reaction consistent with the presence of
      anti-Fc epsilonRIalpha autoantibodies. These autoantibodies have been reported to
      be present in >45% of patients with CIU. Their functional role in the
      pathogenesis of CIU remains poorly understood. OBJECTIVE: Because of the
      therapeutic refractory nature of this patient's CIU requiring high doses of
      corticosteroids, it was decided to initiate treatment with intravenous
      cyclophosphamide (CTX) in an attempt to eradicate autoantibody-producing B
      lymphocyte clones. This therapeutic approach has been previously successful in
      other autoantibody-mediated disorders such as type II acquired angioedema and
      factor VIII deficiency. RESULTS: Initial treatment consisted of 500 mg CTX
      intravenously followed by increases of 100 mg every 2 weeks, with the maximum
      dose reaching 1,500 mg once a month, which represents approximately 20% of the
      dose administered during systemic cancer chemotherapy. Within 7 months there was
      a complete clinical remission and prednisone was discontinued. Repeat
      intracutaneous testing to autologous serum was negative, consistent with an
      abrogated autoantibody response. The patient has not experienced a recurrence of
      CIU at the time of this report. CONCLUSION: This index case suggests that
      intravenous CTX may be effective in alleviating autoantibody-associated CIU in
      corticosteroid-dependent patients refractory to conventional therapies.

PMID- 12197583
TI  - Blood tests for allergies.

PMID- 12197582
TI  - Immediate cutaneous hypersensitivity after treatment of tattoo with Nd:YAG laser:
      a case report and review of the literature.
AB  - BACKGROUND: To our knowledge this is the first reported case of an immediate
      cutaneous reaction to Q-switched neodymium:yttrium-aluminum-garnet (Nd:YAG) laser
      tattoo removal. A 26-year-old female presented with two 6-year-old tattoos placed
      at different times. These were of different colors and had remained entirely
      asymptomatic since placement. There was a Mardi Gras mask on her thigh and a
      Tasmanian devil on her chest. With laser treatment of the Tasmanian devil, she
      experienced no untoward effects. However, with treatment of the Mardi Gras mask
      tattoo, she developed an extensive urticarial and indurated reaction 30 minutes
      posttreatment. The identical reaction occurred twice with subsequent laser
      treatments. Dermatology consulted allergy to provide prophylaxis against possible
      systemic reaction with subsequent Nd:YAG laser therapy. The patient was treated
      with 3 days of prednisone, cetirizine, and ranitidine before subsequent laser
      treatments. Prophylactic treatment suppressed all subsequent reactions to laser
      therapy. RESULTS: Delayed hypersensitivity to tattoo pigments occurring days to
      weeks after placement is well documented. There are no previous reports of
      immediate hypersensitivity during placement or laser removal. However, there are
      two previous reports of local and systemic delayed reactions after laser therapy.
      CONCLUSIONS: As far as we know, this is the first case report of immediate
      hypersensitivity after Nd:YAG laser treatment of a tattoo. Prophylactic treatment
      with steroids and antihistamines prevented reactions with subsequent laser
      treatments. Reactions after laser removal are rare, but may increase as
      popularity of skin art increases with the need for subsequent removal.

PMID- 12197584
TI  - Redroot pigweed.

PMID- 12197585
TI  - The protective effects of community involvement for HIV risk behavior: a
      conceptual framework.
AB  - This paper presents a conceptual framework of the protective effects of community
      involvement in HIV/AIDS-related groups and organizations for HIV sexual risk
      behavior among gay and bisexual men. The framework delineates hypotheses for
      future research, and provides a guide for prevention programs based on the active
      and direct involvement of participants, particularly communities of color. The
      framework (1) argues that community involvement moderates the association between
      three socio-structural risk factors (i.e. poverty, homophobia and racism) and
      sexual risk behavior; (2) posits that community involvement in HIV/AIDS reduces
      sexual risk behavior via its effects on four mediating factors (i.e. peer norms,
      self-efficacy, positive self-identity and alienation); (3) proposes five socio
      cultural barriers to and facilitators of community involvement in HIV/AIDS (i.e.
      motives for participation, poverty, acculturation, stigma and perceived
      opportunities); and (4) addresses burnout as one potential negative consequence
      of community involvement in HIV/AIDS-related organizations and groups. The
      conceptual framework advances the understanding of HIV sexual risk behavior by
      integrating both its socio-structural risk and protective factors. It contributes
      to health education by specifying how interventions based on collective action
      (e.g. community involvement) for social change may be effective in generating
      healthy behaviors at individual and community levels.

PMID- 12197586
TI  - Behavior of caregivers to protect their infants from exposure to the sun in
      Queensland, Australia.
AB  - Exposure to the sun by infants has been demonstrated to increase the risk of the
      development of melanoma and other skin cancers later in life. A cohort of 508
      women who delivered healthy Caucasian babies were followed up at 1 year to
      determine their knowledge, attitudes and practices regarding sun protection
      towards themselves and their child. In addition, the 1-year-old infants were
      assessed by a trained nurse for the number of nevi they had on their skin.
      Results indicate caregivers reported a high level of sun-protection practices
      towards their child, with 93% of the caregivers reporting usually or always
      placing the child in the shade when going outside. Further, 81% of the caregivers
      reported usually or always placing a hat on the child, while 64% reported usually
      or always applying sunscreen to the child's exposed skin. Interestingly, only 61%
      of the caregivers reported that they stayed in the shade to reduce sun exposure
      and only 42% wore a hat when out in the sun. Mother's own personal sun-protection
      methods predicted the method of sun protection that she would most likely use for
      the child. While children appear to be reasonably protected from the sun, they
      are influenced by their mother's own behaviors.

PMID- 12197587
TI  - Learning the relationship between smoking, drinking alcohol and the risk of
      esophageal cancer.
AB  - This study examined the effect of outcome feedback on learning the multiplicative
      relationship between daily intakes of tobacco and alcohol, and the risk of
      esophageal cancer. In the first of two experiments, 65 French adults judged the
      risk of esophageal cancer associated with combinations of five levels of intake
      of tobacco and five of wine. They made these judgments both before and after
      learning sessions in which they were shown the actual risk for each vignette. In
      the second experiment, 35 French adults underwent the same testing and learning,
      and were re-tested twice 1 month later. The study hypotheses were supported.
      First, prior to the learning sessions, the participants used a subadditive rule
      to combine the perceived risk of esophageal cancer from smoking and drinking.
      Second, they learned after only one training session to change to the
      multiplicative rule that is consistent with epidemiological data. Third, this
      learning persisted for 1 month. This methodology may prove useful in correcting
      people's underestimation of their health risks.

PMID- 12197588
TI  - Schistosomiasis, helminth infection and health education in Tanzania: achieving
      behaviour change in primary schools.
AB  - Over a period of one school year a study was carried out into the feasibility and
      effectiveness of introducing active teaching methods into primary schools in
      Tanzania with a view to enhancing health education. The Lushoto Enhanced Health
      Education Project had as a focus personal hygiene with reference to the control
      of schistosomiasis and helminth infections. When a randomly selected group of
      children were compared with a comparison group there was evidence of changes in
      both knowledge and health-seeking behaviour. The passing of messages from
      children to the community met with mixed results. The observed changes were still
      evident over 1 year after the project had ended.

PMID- 12197589
TI  - Differences in impact between a family- versus an individual-based tailored
      intervention to reduce fat intake.
AB  - The present study investigates the impact of a tailored nutrition intervention on
      the reduction of fat intake and on psychosocial determinants of fat intake.
      Furthermore, differences in impact between a family-based intervention (tailoring
      two family members, one adult and one child, simultaneously) and an individual
      based intervention (tailoring one family member, one adult or one child) were
      studied. Analyses were conducted among 180 respondents, comparing 44 adolescents
      in the family condition with 50 adolescents in the individual condition and 44
      parents in the family condition with 40 parents in the individual condition.
      Respondents in both conditions reported positive reactions towards the tailored
      fat feedback letters. Tailored fat feedback resulted in significantly more
      positive psychosocial determinants of fat intake and, among respondents with high
      fat intake at baseline, in a significant decrease in percent energy from fat.
      Parents in the family-based intervention group reported higher social support
      scores at post-test. No differences in post-test fat intake were found between
      the two study conditions. It is concluded that the results further illustrate the
      potential of tailored fat feedback, but the results do not provide evidence for
      superiority of family-based tailoring above individual-based tailored
      interventions for fat. Further research may be aimed at investigating the impact
      of comprehensive tailored family interventions, in which more than two family
      members participate.

PMID- 12197590
TI  - Physical activity intervention: a transtheoretical model-based intervention
      designed to help sedentary young adults become active.
AB  - Physical activity levels in young adults are low. Research supports the use of
      the Transtheoretical Model of behaviour change (TM) in designing physical
      activity interventions. This study used a pre-post randomized control design to
      investigate the effectiveness of a self-instructional intervention for helping
      sedentary young adults to initiate physical activity. Post-intervention,
      significantly more of the experimental group (80%), in comparison to the control
      group (68%), improved their exercise stage of change (SOC) from baseline (P <
      0.05). Discriminant analyses revealed that discrimination between stage
      improvement/non-improvement was possible using the processes of change data.
      Stage improvers scored significantly higher on all of the behavioral and four out
      of five of the cognitive processes of change. For stage improvers, the processes
      of self-re-evaluation and self-liberation were most frequently used, whilst
      social liberation was used significantly more by the experimental than the
      control group. This inexpensive, self-instructional intervention, based on the TM
      and the 'active living message', is an effective method of assisting sedentary
      young adults to progress through the exercise SOC.

PMID- 12197591
TI  - Will the 'principles of effectiveness' improve prevention practice? Early
      findings from a diffusion study.
AB  - This study examines adoption and implementation of the US Department of
      Education's new policy, the 'Principles of Effectiveness', from a diffusion of
      innovations theoretical framework. In this report, we evaluate adoption in
      relation to Principle 3: the requirement to select research-based programs.
      Results from a sample of 104 school districts in 12 states indicate that many
      districts appear to be selecting research-based curricula, but that the quality
      of implementation is low. Only 19% of the responding district coordinators
      indicated that schools were implementing a research-based curriculum with
      fidelity. Common problems included lack of teacher training, lack of requisite
      materials, use of some but not all of the required lessons and teaching
      strategies, and failure to deliver lessons to age-appropriate student groups.
      This study represents the first attempt to assess the quality of implementation
      of research-based programs as required by the Principles of Effectiveness. We
      conclude that low levels of funding, inadequate infrastructure, decentralized
      decision making and lack of program guidance have contributed to the slow
      progress in improving school-based prevention.

PMID- 12197592
TI  - The effectiveness of school-based sex education programs in the promotion of
      abstinent behavior: a meta-analysis.
AB  - This review presents the findings from controlled school-based sex education
      interventions published in the last 15 years in the US. The effects of the
      interventions in promoting abstinent behavior reported in 12 controlled studies
      were included in the meta-analysis. The results of the analysis indicated a very
      small overall effect of the interventions in abstinent behavior. Moderator
      analysis could only be pursued partially because of limited information in
      primary research studies. Parental participation in the program, age of the
      participants, virgin-status of the sample, grade level, percentage of females,
      scope of the implementation and year of publication of the study were associated
      with variations in effect sizes for abstinent behavior in univariate tests.
      However, only parental participation and percentage of females were significant
      in the weighted least-squares regression analysis. The richness of a meta
      analytic approach appears limited by the quality of the primary research.
      Unfortunately, most of the research does not employ designs to provide conclusive
      evidence of program effects. Suggestions to address this limitation are provided.

PMID- 12197593
TI  - Esmolol protects the myocardium and facilitates direct version intracardiac
      operation with a beating heart.
AB  - In recent years there has been renewed interest in beating heart surgery using
      the ultra-active and selective beta1-blocker, esmolol. However, there has not
      been a report of its use in direct version intracardiac surgery with beating
      heart. Twenty-four patients undergoing elective direct version intracardiac
      surgery (mitral valve replacement) were divided randomly into 2 groups: control
      group (normothermia cardiopulmonary bypass (CPB) direct version intracardiac
      beating heart surgery) and esmolol group (normothermia CPB direct version
      intracardiac beating heart surgery and intravenous esmolol drip during CPB to
      maintain heart rate at 30-50 beats/min). Steady hemodynamic parameters were
      maintained in both groups; however, the doses of dopamine used in control group
      were larger than those for the esmolol group (p<0.01). The myocardial
      ultrastructure was well maintained in both group, but the scores for myocardial
      mitochondria, glycogen grading and counting and the amount of adenosine
      triphosphate were higher in the esmolol group (p<0.05). There was no significant
      change in the malondialdehyde level in either group (p>0.05). Using esmolol in
      direct version intracardiac beating heart surgery protects the myocardium and
      facilitates the operation.

PMID- 12197594
TI  - Cardioprotective effects of lowering oxygen tension after aortic unclamping on
      cardiopulmonary bypass during coronary artery bypass grafting.
AB  - The effect on myocardial reperfusion injury of reducing oxygen tension during
      reperfusion on cardiopulmonary bypass (CPB) in coronary artery bypass grafting
      (CABG) was examined at the same time as the influence of diltiazem during CPB was
      evaluated. A prospective, randomized trial evaluated the hemodynamic and
      myocardial metabolic recovery in 3 groups of patients undergoing elective CABG;
      subjects were randomly allocated on the basis of oxygen tension during
      reperfusion after aortic unclamping: group 1 (n=10) hyperoxic reperfusion (oxygen
      tension [PO2]=450-550 mmHg); group 2 (n=10): hyperoxic reperfusion and subsequent
      continuous infusion of diltiazem (0.5 microg/kg); group 3 (n=10): lowering
      reperfusate PO2 (PO2=200-250 mmHg). Hemodynamic and myocardial metabolic
      measurements were taken at 6 preset times: before starting the surgical procedure
      and at 30 min and 3, 9, 21, and 45 h after discontinuation of CPB. The cardiac
      index in the lowering reperfusate PO2 group was higher than that of the hyperoxic
      reperfusion groups at 30 min and 3 h after CPB, and malondialdehyde and troponin
      T were significantly lower at 30 min and 3 h, respectively. In comparison with
      the hyperoxic + diltiazem group, the hemodynamic and myocardial recovery in the
      lowering reperfusate PO2 group was improved for about 3 h after CPB. Reduced
      oxygen tension during reperfusion after aortic unclamping on CPB is more
      effective against myocardial injury than a calcium antagonist in the short term.
      It is a convenient and safe management technique that can reduce morbidity and
      mortality, especially in the severely compromised heart.

PMID- 12197595
TI  - Suppressive effect of the Gly389 allele of the beta1-adrenergic receptor gene on
      the occurrence of ventricular tachycardia in dilated cardiomyopathy.
AB  - Beta-1-adrenergic receptor (beta1-AR) blockers reduce both the incidence of
      sudden death and the ventricular volume in heart failure. In vitro, the Gly389
      variant of beta1-AR mediates less adenylyl cyclase activities than the Arg389
      variant, so Arg389Gly polymorphism was investigated with regard to the genesis,
      progression, or arrhythmogenesis of dilated cardiomyopathy (DCM). Allele and
      genotype frequencies of the Arg389Gly polymorphism were determined in 163 DCM
      patients and 157 age- and sex-matched controls. There were no differences in
      genotype and allele frequencies between patients and controls. Echocardiograms,
      left ventriculograms and 24h-Holter electrocardiograms were evaluated in the DCM
      patients and none of the clinical indices, other than ventricular tachycardia
      (VT), differed among the 3 genotypes. The Gly389 allele was more frequent in the
      VT(-) group than in the VT(+) group (0.46 vs 0.24, p=0.001). In univariate
      analysis, the odds ratio for VT in patients carrying 1 or 2 copies of the Gly389
      allele was 0.29 ([95% confidence interval, 0.13-0.64], p=0.002), when compared
      with the Arg389 homozygotes. The Gly389 variant supressed the occurrence of VT in
      DCM, suggesting that this allele confers a decreased risk of sudden death.

PMID- 12197596
TI  - Ultrasonic myocardial tissue characterization in patients with hypertrophic
      cardiomyopathy and pressure-overloaded hypertrophy by backscattered energy
      temporal analysis.
AB  - This study measured integrated backscatter (IB) values in the subendocardium and
      subepicardium of patients with hypertrophy using the newly developed
      Backscattered Energy Temporal Analysis (BETA) system, and evaluated the
      differences of acoustic properties according to etiology. Twenty-one patients
      with hypertrophic cardiomyopathy (HCM), 16 with pressure-overloaded hypertrophy
      (POH), and 21 controls were studied. M-mode formatted IB images were obtained
      using BETA and the region of interest (ROI), automatically divided into
      epicardial and endocardial halves of the myocardium, was placed in the
      ventricular septum and posterior wall. Values for the cyclic variation of IB
      (CVIB) in the entire ROI and in each half of the ROI were obtained. CVIB
      significantly decreased in the ventricular septum in HCM and POH compared with
      normal subjects, but there were no significant differences between HCM and POH.
      In the posterior wall, the CVIB was less in the subendocardium than in the
      epicardium in POH, and was also less than in normal subjects (7.0+/-1.7 dB vs
      8.6+/-1.9 dB and 8.8+/-2.1 dB, p<0.05, respectively). Separate ultrasonic tissue
      characterization of the subendocardium and subepicardium provides further
      etiological information of various heart diseases.

PMID- 12197598
TI  - Evidence of a cellular protective effect by antecedent angina independent of
      collateral flow recruitment during coronary angioplasty in humans.
AB  - The main aim of this study was to elucidate whether the beneficial effect of
      antecedent angina is a cellular protective effect or the result of an increase of
      collateral flow. Of 42 patients with angina who underwent percutaneous
      transluminal coronary angioplasty (PTCA) for proximal left anterior descending
      artery (LAD) stenosis, 22 had experienced antecedent anginal pain (AP) within 7
      days prior to PTCA. 99mTc-sestamibi was injected during balloon inflation, and
      quantitative analysis of ischemic severity during coronary occlusion was
      calculated (SS). An electrocardiogram was recorded during ballooning to calculate
      the sum of ST elevation (sumST). SumST was significantly reduced in patients with
      AP compared with patients without AP (1.88+/-0.89 mV vs 1.18+/-0.74 mV,
      p=0.0088); however, no difference was observed in defect severity. A close
      correlation was observed between SS and sumST in both groups. The multivariate
      regression model demonstrated that both a large SS (p<0.0001) and the absence of
      preceding AP (p=0.001) were significantly related to the elevation of sumST.
      Recent angina can render the myocardium more resistant to subsequent ischemia
      during angioplasty and is true preconditioning rather than simply an increase of
      flow.

PMID- 12197597
TI  - Coronary disease morphology and distribution determined by quantitative
      angiography and intravascular ultrasound--re-evaluation in a cooperative
      multicenter intravascular ultrasound study (COMIUS).
AB  - Although previous studies have demonstrated that even quantitative coronary
      angiography (QCA) can not provide accurate disease morphology, there has not been
      a systematic comparison of disease morphology determined by QCA and intravascular
      ultrasound (IVUS), particularly in Japanese patients. Therefore, the present
      study prospectively examined patients in a multicenter cooperative study. A total
      of 491 coronary sites from 562 patients (446 men, 116 women; mean age, 64+/-11
      years) who underwent coronary interventions were enrolled. The target lesions
      (>50% diameter stenosis) were evaluated pre-operatively by both QCA and IVUS
      operating at 30-40 MHz and the percent area stenosis, eccentricity index (EI) and
      lesion length were determined. The minimal (min) and maximal (max) distances from
      the center of the stenotic lesion to the outline of the vessel wall were
      measured, and the EI was calculated by the formula: [(max - min)/max]. By QCA,
      lesion length was determined by measuring the distance between the proximal and
      distal shoulders of the lesion. When the lesions were observed by IVUS with a
      motorized pull-back system, the length was calculated by multiplying the time for
      observation of the disease and 0.5 or 1 mm/s. Although the severity of the
      stenosis determined by QCA (86+/-10%, mean +/- SD) did not differ from that by
      IVUS (83+/-13%), there was no correlation between them (r=0.32, y=0.25x+65) and
      the correlation did not improve when lesions with remodeling, enlargement (n=176)
      or shrinkage (n=79) were omitted from the calculation. The EIs by QCA and IVUS
      were 0.51+/-0.26 and 0.52+/-0.22, respectively (NS), and there was no correlation
      between them (r=0.30, y=0.36x+33). However, when the lesions with remodeling were
      excluded, the correlation greatly improved (r=0.80, y=0.84x+10.6, p<0.05). Lesion
      length determined by QCA (12.4+/-6.1 mm) was significantly shorter than that by
      IVUS (16.3+/-8.9 mm, p<0.01). These results demonstrate that coronary angiography
      significantly misinterprets disease morphology in terms of severity, eccentricity
      and length, in part because of vessel remodeling that can be accurately
      determined only by IVUS.

PMID- 12197599
TI  - High incidence of device-related and lead-related complications in the dual
      chamber implantable cardioverter defibrillator compared with the single-chamber
      version.
AB  - Recently, the routine use of dual-chamber implantable cardioverter defibrillators
      (DC-ICD) has been advocated over the single-chamber version (SC-ICD), but there
      are few reports of the frequency of complications between the 2 types of ICDs.
      Between July 1997 and April 1999, 178 consecutive patients underwent implantation
      of either a transvenous SC-ICDs (n=104) or a DC-ICDs (n=74). Twelve (16%) of the
      74 patients with a DC-ICD had a total of 16 major complications compared with 6
      (6%) of the 104 patients with a SC-ICD (p=0.01). The 16 DC-ICD complications
      included atrial lead dislodgment (4), ventricular lead malfunction (4), and
      pocket infection/hematoma (3), and the 6 SC-ICD complications included
      ventricular lead dislodgment (2) and pocket hematoma (3). Patients with a DC-ICD
      had less left ventricular function (29% vs 35%, p=0.035) and a higher prevalence
      of non-ischemic cardiomyopathies (48% vs 28%, p=0.0076). In conclusion, the DC
      ICD may have a higher frequency of device- and lead-related major complications.

PMID- 12197600
TI  - Comparison of accelerometry and oxymetry for measuring daily physical activity.
AB  - To assess the validity of accelerometry in measuring daily physical activity, the
      energy consumption calculated by accelerometry, with respiratory gas analysis as
      a reference, was evaluated in 45 non-athletes during various exercise tests.
      Subjects were required to (1) walk on a treadmill ergometer at various speeds,
      (2) walk on a treadmill ergometer at a fixed speed and with a stride of 20% more
      or 20% less than that when walking freely, (3) walk on a treadmill ergometer at a
      fixed speed wearing either sneakers or leather-soled shoes, and (4) cycle on a
      bicycle ergometer. There were strong linear relationships between the
      measurements during the progressively graded treadmill test, with an overall
      Pearson correlation coefficient of 0.97. The mean estimated difference ranged
      from -0.77 to 0.27 kcal/min and the coefficients of variation from 13.2% to
      22.2%. However, the difference between the methods was not negligible for
      individual subjects. Accelerometry overestimated energy expenditure during short
      step walking, and underestimated it during long-step walking. No significant
      difference in energy expenditure was found according to the type of shoes worn.
      Cycling activity was not recorded by accelerometry. Accelerometry is a reasonably
      accurate and feasible method for evaluating the physical activities of non
      athletes, and could be a common tool for epidemiological research and health
      promotion despite its limitations.

PMID- 12197601
TI  - Combined coronary artery bypass grafting on the beating heart and abdominal
      aortic aneurysm repair.
AB  - Abdominal aortic aneurysm (AAA) is commonly associated with coronary artery
      disease (CAD). Eleven patients underwent the combined operation of coronary
      artery bypass grafting (CABG) on the beating heart and AAA repair: 10 underwent
      off pump CABG and 1 patient required centrifugal pump and pulmonary assist with
      closed circuit because of unstable hemodynamics. All cases were discharged
      without severe complications and with patent coronary bypass grafts.

PMID- 12197602
TI  - Comparison of the in vivo electrophysiological and proarrhythmic effects of
      amiodarone with those of a selective class III drug, sematilide, using a canine
      chronic atrioventricular block model.
AB  - Amiodarone effectively blocks both the sodium and calcium channels and beta
      adrenoceptors, in addition to blocking several potassium currents including IKr,
      IKs, Ito, IK1, IKACh and IKNa. The incidence of clinical torsade de pointes (TdP)
      associated with amiodarone has been reported to be low and the present study
      compared the proarrhythmic potential of amiodarone with that of a selective IKr
      channel blocker, sematilide, using a canine chronic atrioventrucular block model.
      Amiodarone or sematilide (3 and 30 mg/kg; n=4 for each group) was administered
      orally without anesthesia under continuous ECG monitoring. Both drugs prolonged
      the QT interval, although the onset was faster for sematilide. The high dose of
      sematilide induced TdP in 3 of 4 animals, which caused their death, but neither
      the low dose of sematilide nor the 2 dosages of amiodarone induced lethal
      ventricular arrhythmias. These results suggest that IKr channel inhibition by
      amiodarone with its additional ion channel blocking action may contribute to the
      prevention of TdP.

PMID- 12197603
TI  - Sheng-Mai-San is protective against post-ischemic myocardial dysfunction in rats
      through its opening of the mitochondrial KATP channels.
AB  - The present study used isolated rat hearts to investigate whether (1) Sheng-Mei
      San (SMS), a traditional Chinese formulation comprising Radix Ginseng, Radix
      Ophiopogonis and Fructus Schisandrae, is protective against post-ischemic
      myocardial dysfunction, and (2) whether the cardioprotective effect of SMS is
      related to scavenging of hydroxyl radicals and opening the mitochondrial KATP
      channels. The excised hearts of male Sprague-Dawley rats were perfused on a
      Langendorff apparatus with Krebs-Henseleit solution with a gas mixture of 95% O2
      and 5% CO2. Left ventricular end-diastolic pressure (LVEDP, mmHg), left
      ventricular developed pressure (LVDP, mmHg), +/-dP/dt (mmHg/s) and coronary flow
      (ml/min) were continuously monitored. All hearts were perfused for a total of 120
      min consisting of a 30-min pre-ischemic period followed by a 30-min global
      ischemia and 60-min reperfusion. Lactate, lactate dehydrogenase (LDH) and 2,5
      dihydroxybenzoic acid (2,5-DHBA) concentrations in the effluent were measured
      during reperfusion. Three days' treatment with SMS (1.67 ml/kg per day) inhibited
      the rise in LVEDP and improved the post-ischemic LVDP and +/-dP/dt significantly
      better than in the untreated control hearts during reperfusion. SMS increased the
      coronary flow at baseline, and during reperfusion. Pretreatment with 5
      hydroxydecanoic acid (5-HD), a mitochondrial KATP channel blocker, abolished the
      inhibition of the rise in LVEDP, the increase in coronary flow and the
      improvement in LVDP and +/-dP/dt induced by SMS. SMS significantly attenuated the
      concentrations of lactate, LDH and 2,5-DHBA during reperfusion, but the
      pretreatment with 5-HD restored them; 5-HD alone did not affect the
      concentrations. SMS improved the post-ischemic myocardial dysfunction through
      opening the mitochondrial KATP channels.

PMID- 12197604
TI  - Oozing-type of left ventricular rupture treated under percutaneous
      cardiopulmonary support without surgical repair.
AB  - A 65-year-old man was admitted to the National Defense Medical College Hospital
      for acute anterolateral myocardial infarction and cardiogenic shock. Emergency
      coronary angiography demonstrated occlusion of the proximal left anterior
      descending artery. Primary percutaneous transluminal coronary angioplasty (PTCA)
      was successfully performed with the support of intra-aortic balloon pumping
      (IABP) and medical treatment to stabilize the patient's blood pressure. On the
      second hospital day, the patient suffered cardiac tamponade. Pericardiocentesis
      showed bloody fluid and revealed that an oozing-type of left ventricular rupture
      had occurred after the myocardial infarction. Cardiogenic shock persisted after
      successful removal of the pericardial effusion. Although the heparinization
      required during percutaneous cardiopulmonary support (PCPS) can increase
      pericardial effusion, PCPS was initiated to correct the systemic hypoperfusion; a
      surgical team was on standby in case massive pericardial effusion resulted, but
      fortunately that did not occur, and cardiac function recovered. The patient was
      weaned successfully from PCPS and IABP and has remained in a satisfactory
      condition for over 1 year. PCPS contributed to the patient's recovery from
      cardiac shock and may have decreased the effusion from the oozing-type rupture by
      reducing ventricular wall tension.

PMID- 12197605
TI  - Interstitial pneumonia induced by ticlopidine.
AB  - A 67-year-old female non-smoker, who had been diagnosed with familial
      hypercholesterolemia associated with severe atherosclerosis of the coronary,
      carotid and vertebral arteries, developed interstitial pneumonia 4 months after
      initiating ticlopidine to inhibit platelet aggregation. The lymphocyte
      stimulation test by ticlopidine was positive and bronchoalveolar lavage fluid
      showed an increase in lymphocytes and a decrease in the CD4+/8+ ratio, suggesting
      potentially undesirable side effects of ticlopidine. Two months after ticlopidine
      therapy was discontinued and prednisolone therapy started, the interstitial
      pneumonia had almost completely resolved. Two patients, one with ticlopidine
      associated bronchiolitis obliterans organizing pneumonia and the other with
      pneumonia with multiple nodules, have been reported to date and the present
      patient is the third reported case of ticlopidine-induced pneumonia. The
      incidence of this side effect may not be so high because approximately 20 years
      have passed since ticlopidine was first marketed in Japan, but because the drug
      is now widely prescribed, this serious clinical side effect should be considered.

PMID- 12197606
TI  - Cerebral embolism in off-pump coronary artery bypass grafting.
AB  - A 64-year-old woman with a history of cerebral infarction from chronic occlusion
      of the middle cerebral artery presented with acute myocardial infarction. Double,
      off-pump coronary artery bypass grafting could not prevent stroke caused by
      atheroembolism from the ascending aorta. The risk of stroke from atheroembolism
      should be taken into consideration when planning coronary artery bypass grafting.

PMID- 12197608
TI  - Oral delivery of proteins: progress and prognostication.
AB  - The delivery of proteins has gained momentum with the development of
      biotechnology sector that provided large-scale availability of therapeutic
      proteins. The availability is mostly due to the advances in recombinant DNA
      technology. The low oral bioavailability, however, continues to be a problem for
      several proteins because of their large molecular size, low permeation through
      biological membranes, and susceptibility to molecular changes in both biological
      and physical environments. The demand for effective delivery of proteins by the
      oral route has brought a tremendous thrust in recent years both in the scope and
      complexity of drug delivery technology. The important therapeutic proteins and
      peptides being explored for oral delivery include insulin, calcitonin,
      interferons, human growth hormone, glucagons, gonadotropin-releasing hormones,
      enkephalins, vaccines, enzymes, hormone analogs, and enzyme inhibitors. This
      article reviews the progress in oral delivery of these proteins, provides
      comments on the strategies to improve their oral bioavailability, and highlights
      their current market trends.

PMID- 12197607
TI  - Coronary arteriovenous fistula presenting as chronic pericardial effusion.
AB  - In August 1998, the patient, a 75-year-old woman, was diagnosed with pericardial
      effusion (PE) during an investigation of cardiomegaly. The PE disappeared after
      the administration of diuretics, but in February 1999, shortness of breath and
      general fatigue developed, and PE was again present. Diagnostic
      pericardiocentesis revealed bloody fluid. Chest computed tomography revealed a
      markedly expanded and tortuous right coronary artery (RCA). Coronary angiography
      (CAG) confirmed a RCA-coronary sinus fistula, and there was a significant step-up
      of O2 saturation at the right atrium. Cardiac tamponade developed soon after CAG,
      so the patient underwent surgical closure of the CAVF. Although a bleeding point
      was not identified, the PE was disappeared after operation. Histopathologically,
      parts of the wall of the fistula were quite thin and erythrocytes and lymphocytes
      had infiltrated the pericardial space. The clinical course and the findings
      indicate that the CAVF caused chronic PE.

PMID- 12197609
TI  - Glycosylated cationic liposomes for cell-selective gene delivery.
AB  - Cationic liposomes have been considered as a potential nonviral vector for gene
      delivery because they possess low immunogenicity, unlike viral vectors. The gene
      transfer efficiency of cationic liposomes is lower than that ofviral vectors, but
      recent advances have shown that it is possible to enhance the gene expression
      levels of cationic liposomes. The main problem with cationic liposomes seems to
      be the lack of organ or cell selectivity because the lung has the highest level
      of gene expression after intravenous injection. Applying cell-specific targeting
      technology to liposomes would improve in vivo gene delivery and reduce any
      unexpected side effects. Both liver parenchymal and non-parenchymal cells
      exclusively express large numbers of high-affinity asialoglycoprotein and mannose
      receptors, respectively. Receptor-mediated gene delivery systems are able to
      introduce foreign DNA into specific cell types in vivo. However, we have
      confirmed that not only the nature of the ligands grafted to carriers but also
      the overall physicochemical properties of the complexes need to be optimized for
      effective cell-selective targeting of plasmid DNA. In this article, we attempt to
      evaluate a gene delivery system based on the physicochemical properties of
      plasmid DNA/glycosylated cationic complexes.

PMID- 12197610
TI  - Nanocapsule technology: a review.
AB  - Nanocapsules are submicroscopic colloidal drug carrier systems composed of an
      oily or an aqueous core surrounded by a thin polymer membrane. Two technologies
      can be used to obtain such nanocapsules: the interfacial polymerization of a
      monomer or the interfacial nanodeposition of a preformed polymer. This article is
      an extended review of these nanocapsule technologies and their applications for
      the treatment of various diseases (including cancer and infections).

PMID- 12197611
TI  - Gravimetric and spectrophotometric determination of some phenothiazine and
      imidazole derivatives in coated tablets and tablets.
AB  - Two drugs in the form of coated tablets: Promazin (promazine hydrochloride) (1)
      and Thioridazin (thioridazine hydrochloride) (2), and tablets Clotrimazolum
      (clotrimazole) (3) were assayed gravimetrically and spectrophotometrically in the
      same process using complexes with ammonium molybdate. Stoichiometry of these
      complexes was established by elemental analysis and analysis of the incineration
      residue (MoO3). The complexes were subsequently characterized using their IR and
      UV spectra and melting points. The active substances of the complexes were also
      determined spectrophotometrically. Using this method Beers Law was found to hold
      for the concentration ranges of 5-40 microg/ml (complex of 1), 5-60 (microg/ml
      (complex of 2) and 2-10 microg/ml (complex of 3). The method was validated in
      terms of precision, linearity, detection limit and quantification limit. The two
      methods of drug determination, used in a single analytical process verify each
      other.

PMID- 12197612
TI  - Infrared spectrum analysis of some flavonoids.
AB  - Infrared spectra of some flavonoids and quercetin and morin sulfonic derivatives
      were recorded. The spectral data of sodium salts of quercetin and morin sulfonic
      acids were interpreted as indicating the near position valency band of the
      carbonyl group in relation to its position in quercetin and morin. The distinct
      shift of this band in quercetin-5'-sulfonic acid (QSA) may probably be a result
      of the occurrence of an intramolecular proton transfer from the sulfonic -SO3H to
      the oxygen of -C=O group.

PMID- 12197613
TI  - Examination of iron (III) and hexacyanoferrate (III) ions as reagents for the
      spectrophotometric determination of promazine and perazine.
AB  - Iron (III) chloride and potassium hexacyanoferrate (III) have been tested as
      reagents for the determination of promazine hydrochloride and perazine. The
      methods are based on the oxidation of phenothiazines by FeCl3 and K3[Fe(CN)6] in
      perchloric acid medium. The optimal conditions for the formation of oxidation
      products of promazine and perazine were examined. The absorption spectra in the
      UV-VIS region were recorded.

PMID- 12197614
TI  - Reactivity of 5-nitro-2-furaldehyde in alkaline and acidic solutions.
AB  - 5-Nitro-2-furaldehyde (NFA) forms in alkaline solutions an anion of nitronic acid
      of (5-nitro-furan-2-yl)-methanediol. Upon acidification (5-nitro-furan-2-yl)
      methanediol (HNFA) appears with pKa=4.6. Then, in a novel irreversible redox ring
      opening reaction, nitrile oxide of alpha-ketoglutaconic acid is formed which
      hydrolyses in acidic solutions. With increasing pH it dimerizes to furoxane or
      polymerizes to hydraxamates. Some of the products were separated and identified
      by IR and NMR spectroscopy, confirmed by elemental analysis.

PMID- 12197615
TI  - Pharmaceutical availability of clobetasol-17-propionate from cream and ointment.
AB  - Kinetics of drug release from both compared preparations available as a cream and
      an ointment, was in vitro studied. A reversed-phase HPLC method was developed for
      the determination of clobetasol-17-propionate in lipophylic bases using
      clobetasol-17-butyrate as an internal standard. Analyses were performed using a
      C18 reversed-phase column with a mobile phase of methanol-water and ultraviolet
      detection at lambda=254 nm. The calibration curve was constructed for the
      concentration range 0.5-40.0 microg/ml. The method is simple, accurate and
      precise.

PMID- 12197616
TI  - Susceptibility to antibiotics and biochemical properties of Desulfovibrio
      desulfuricans strains.
AB  - Susceptibility to several antibiotics and biochemical properties of intestinal
      and soil strains of Desulfovibrio desulfuricans bacteria were investigated using
      the tests: ATB ANA, Sceptor Anaerobic MIC/ID and API ZYM. It was demonstrated
      that the D. desulfuricans strains were resistant to penicillin, cefoxitin,
      clindamycin, metronidazole, erythromycin, rifampicin and teicoplanin. The strains
      initially susceptible to imipenem became resistant to this drug following 72 h
      incubation with it. Of 25 analyzed antibiotics there was none that after 72 h
      action on the bacteria was effective in relation to all of the investigated
      strains. The differences in susceptibility of D. desulfuricans strains to
      antibiotics were not associated with the strains' biochemical properties.

PMID- 12197617
TI  - Potato starch derivatives with some chemically bound bioelements.
AB  - Metal alkoxides [Cr(III), Mg(II), Mo(V), V(III), and W(V)] taken in 1:1 equimolar
      proportions, calculated per one D-glucose unit, reacted with a pregelatinized
      starch in microwave assisted processes into the corresponding starch cationic
      metal derivatives. In each case, the crosslinking occurred as a consequence of
      the substitution of two alkoxide groups in the metal alkoxide reagents with two D
      glucose units. Involvement of the 6-CH2OH moiety of the D-glucose units in
      formation of the valence bond with the metal cation was the most likely, but the
      metal cation was additionally coordinated to the other hydroxyl groups of the D
      glucose units. Chromium(III) and vanadium(II) complexes hydrolysed in full by
      their contact with water, whereas the other metal complexes hydrolysed only in
      part.

PMID- 12197618
TI  - Technology and physico-chemical evaluation of solid ocular inserts containing
      sulfadicramide and hyaluronic acid.
AB  - Synthetic lipophilic membranes, containing sulfadicramide (SDC), disodium salt of
      hyaluronic acid and disodium salt of taurolithocholic acid were prepared as
      described (Furst et al.). Rate constants of SDC release from the above membranes
      and its apparent permeability coefficients through the comea isolated from the
      pig's eyes were determined.

PMID- 12197619
TI  - Triterpenes and sterols in the flowers and leaves of Prunus spinosa L.
      (Rosaceae).
AB  - From the flowers of Prunus spinosa L. a mixture of alpha- and beta-amyrine, a
      mixture of ursolic and oleanolic acids, ursolic acid, a mixture of beta
      sitosterol, gamma-sitosterol and stigmasterol and beta-sitosterol 3-O-beta-D
      glucopyranoside were isolated. Their structure was determined by spectroscopic
      methods (GC/MS, IR, 1H and 13C NMR). Chromatographic methods (GC, HPLC, TLC) were
      employed to determine the presence of the listed compounds in the leaves. Also,
      the content of beta-sitosterol, ursolic and oleanolic acids in the leaves and
      flowers of blackthorn was determined by GC/MSD method.

PMID- 12197621
TI  - Comparative studies and quantitative determination of flavonoid compounds in the
      flowers of some species of the Aquilegia L. genus.
AB  - The flowers of nine species of Aquilegia L. genus: A. hybrida Scott-Eliot, A.
      olympica Boiss., A. flabellata Sieb et Zucc., A. alpina L., A. atrata W.D.J.
      Koch, A. vitoleili L., A. caerulea James, A. canadensis L., A. pyrenaica D.C.,
      were co-chromatographed with the flavonoids and the extract from A. vulgaris L.
      The content of flavonoids in these species were determined by the Christ-Muller
      method.

PMID- 12197620
TI  - Densitometric analysis of kawain in kava-kava root extracts.
AB  - A thin layer chromatographic-densitometric method for the identification and
      determination of kawain in a mixture of kavalactones obtained from a methanol
      extract of kava-kava roots (Piper methysticum) was developed. The main compounds
      present in the extract were separated with good results using silica gel F 254
      coated TLC plates as the stationary phase and hexane-dioxane-butyl acetate
      ammonia 25% (7:2:3:0.5 v/v/v/v) as the mobile phase. The qualitative
      identification and quantitative measurement of kawain were obtained by UV
      measurements at lambda=250 nm. The described method demonstrates very high
      sensitivity with the limit of detection established at 20 ng. 99.38% of the
      kawain was recovered and the concentration range showed a linearity from 0.0005%
      to 0.004%. Under these conditions, the percent of kawain in the presence of other
      kavalactones in the prepared extracts (I-VII), was determined. Similar results
      were obtained for all extracts, with the kawain content ranging from 1.01% to
      1.16%.

PMID- 12197622
TI  - Study of interaction of gastrointestinal agents in the presence of cytoprotective
      drugs. Part II. In vitro study on the adsorption of selected spasmolytic drugs on
      sucralfate.
AB  - The subject of the research was the adsorption of selected musculotropic and
      cholinolytic spasmolytics on a cytoprotective drug--sucralfate. Adsorption
      evaluation was made by a static method, in vitro, the environment reaction, the
      concentrations of the tested drugs and the sucralfate form being taken into
      account. The obtained results prove that the analysed therapeutic substances are
      adsorbed on the sucralfate in all pH. The highest bonding capacity was observed
      in tests at pH=3.6, in the presence of sucralfate, which at this pH occurs in the
      form of suspension. The lowest capacity was at pH=1.5 in the presence of
      sucralfate in the paste form. In the group of the tested drugs, scopolamine
      butylbromide is adsorbed best, drotaverine hydrochloride little less and
      papaverine hydrochloride least of all.

PMID- 12197623
TI  - Tropane alkaloids in pharmaceutical and phytochemical analysis.
AB  - Alkaloids with tropane skeleton, present in many species of Solanaceae family,
      constitute important raw materials for variety of pharmaceutical preparations.
      Although basic facts concerning chemistry and pharmacology of these compounds
      date back to XIX century, the wealth of data, accumulated recently, has
      challenged many established opinions, particularly in the field of biogenesis.
      Advances in analytical techniques which made this progress possible are
      discussed, in reference to contemporary requirements for specification of active
      pharmaceutical ingredients.

PMID- 12197624
TI  - Effect of oestrogen replacement therapy on bone mass in post-menopausal
      Bangladeshi women.
AB  - The female population comprises 48.66% of our total population, of which 10.30%
      are above the age of 49, many of whom are post-menopausal. Menopause is
      associated with bone-loss and its consequences. Hormone replacement therapy
      (HRT), particularly replacement of estrogen, prevents bone-loss. We undertook
      this prospective case-controlled study to find out whether or not HRT is
      beneficial to our women. A total of 106 patients were studied, amongst them 60
      were cases and 46 were controls. The women in the first group were given either
      conjugated equine estrogen alone (surgical menopause group) or conjugated equine
      estrogen plus cyclical progesterone (natural menopause group). Results showed
      that there was 4.29% increase in bone mineral density in women who received
      hormone replacement therapy (HRT). This increase was 5.23% in early and 3.56% in
      late menopause group. Women with natural menopause gained more bone mass (4.22%)
      than women with surgical menopause (3.9%). Our results also showed that women who
      denied HRT (controls) lost bone mass (5.26%), the loss was more in those with
      surgical menopause (6.24%) than those with natural menopause (4.87%). Therefore
      it can be concluded that post-menopausal hormone replacement therapy prevents
      bone-loss. However, to evaluate the beneficial effect of long-term HRT, further
      studies with larger samples are recommended.

PMID- 12197625
TI  - Necrosectomy followed by closed cavity lavage for necrotising pancreatitis-
      report of three cases.
AB  - Necrotizing Pancreatitis is a life threatening condition involving pancreas,
      peripancreatic and retroperitoneal tissues. It's serious regional and systemic
      involvement causes multiple organ or system failure. Planned and carefully
      performed necresectomy followed by closed cavity lavage can significantly reduce
      the mortality and morbidity of this catastrophic condition. Meticulous
      preoperative resuscitation, preparation and operative necrosectomy followed by
      continuos irrigation in the postoperative period were done in three consecutive
      patients. The operative procedure including postoperative management and follow
      up is reported and analyzed.

PMID- 12197626
TI  - Inflammation and glandular proliferation in hyperplastic prostates: association
      with prostate specific antigen value.
AB  - A series of 73 cases of surgically resected prostatic tissue were histologically
      diagnosed as nodular hyperplasia, of which 10 (13.69%) cases had chronic
      prostatitis. The mean value of prostate specific antigen in prostatic hyperplasia
      without chronic prostatitis and prostatic hyperplasia with chronic prostatitis
      were 6.09 ng/ml and 13.61 ng/ml respectively. A statistically significant
      difference of prostate specific antigen level between these two groups were noted
      (P<.05). The degree of glandular proliferation in nodular hyperplasia was
      subjectively assessed and was recorded as mild, moderate or severe degree of
      proliferation. The mean value of prostate specific antigen were 3.28 ng/ml in
      patients with mild proliferation, 7.21 ng/ml in those with moderate proliferation
      and 14.78 ng/ml in those with severe proliferation. A significant association
      between prostate specific antigen level and degree of glandular proliferation was
      found (P<.05). Chronic prostatitis and glandular proliferation are the two
      important factors contributing to serum prostate specific antigen elevation in
      hyperplastic prostates.

PMID- 12197628
TI  - Dissecting the contradictory findings of angiotensin converting enzyme genetic
      polymorphism with blood pressure and hypertension.
AB  - The studies on the association of deletion/insertion (D/I) polymorphism of
      angiotensin converting enzyme (ACE) gene with blood pressure and hypertension
      reported contradictory results. We review the articles that considered blood
      pressure or hypertension as the main outcome measure to have an overview of the
      situation. There is heterogeneity of allele frequencies of ACE locus among ethnic
      groups. In descending order of D allele frequencies, ethnic groups are: Gulf
      Bedouin (0.657), Black (0.597), White (0.577), Chinese (0.400), Japanese (0.377),
      Bangladeshi (0.374) and Indian Sikh (0.373). Multiple studies were available for
      the Caucasians and Japanese with relatively large sample sizes. Three out of five
      studies in the Caucasians found association either in males or in females with
      blood pressure or hypertension. None of the three Japanese studies observed an
      association. So, ACE locus may be considered a marker for blood pressure or
      hypertension in the Caucasians but not in the Japanese. This racial difference is
      not surprising, because heterogenecity of ACE activity according to ACE genotypes
      has been reported among ethnic groups, and important differences in environmental
      factors persist. Studies in other populations were either small or sampling
      procedures were not adequately described. Given that the studies varied in
      designs, settings, sample size, and adjustment for confounding variables,
      adequately powered large-scale multicentre, multi-ethnic population-based studies
      using same method are required to resolve this contradiction.

PMID- 12197627
TI  - Correlation of ultrasonographic findings with ultrasound guided fine needle
      aspiration of liver lesion.
AB  - Ultrasonographic findings of liver were correlated with cytological findings in a
      series of 50 patients. Multiple lesions described by ultrasonography and
      suggested as HCC/TB were proved to be metastatic in 60% cases and hepatocellular
      carcinoma in 40% cases by cytological examination. Multiple lesions suggested as
      metastatic lesions in ultrasonography was proved as such by cytology in 83%
      cases. Solitary lesion suggested as neoplastic in ultrasonography was proved as
      such in cytology in 90% cases. Of the 2 patients suggested as diffuse parenchymal
      lesion revealed cytological findings of cirrhosis in one case and that of TB in
      other. Serum alpha-feto protein and Carcinoembryogenic antigen (CEA) was done in
      all the cases. Serum alpha-feto protein was higher in hepatocellular carcinoma
      and CEA was higher in metastatic lesions. Ultrasound guided fine needle
      aspiration of liver can play more role in diagnosis and classification of liver
      disease than ultrasonographic comment alone, as it requires greater degree of
      precision to reach diagnostic accuracy.

PMID- 12197629
TI  - Depression after stroke-analysis of 297 stroke patients.
AB  - Stroke is commonly followed by some form of psychiatric disturbance. Association
      and severity of depression at the 3rd and 12th months after stroke in patients
      and controls were compared. Two registers of stroke patients were maintained over
      2 years period in two different centers--one in Barisal Town and other in Mitford
      Hospital, Dhaka. A total of 297 first-ever strokes were registered. These
      patients were called back at the 3rd and 12th month interview and assessment.
      Beck's Depression Inventory (BDI), with 10 as the cut off point for depression,
      was applied to 161 of 212 survivors at the 3rd month and to 156 of 195 survivors
      at the 12th month. At the 3rd month, 41% of patients and 18% of controls were
      depressed (P<.001) and the difference was maintained at the 12th month 42% versus
      19% (P<.05). Univariate risk factors for depression at the 3rd month were female
      sex, severe prognostic score at the onset of stroke, age more than 70 years,
      family history of stroke and living alone after stroke. Depression was common
      among stroke survivors at the 3rd months and its rate did not decrease at 1 year
      follow-up. Depression could be decreased if post-stroke rehabilitation services
      are improved. After the development of depression earlier diagnosis and
      management help a lot to the patients and care givers.

PMID- 12197630
TI  - Immunophenotyping of leukocytes in peripheral blood of BALB/c mice infected with
      mouse herpesvirus isolate 72.
AB  - We characterized leukocytes in peripheral blood of BALB/c mice infected with
      mouse herpesvirus isolate 72 (MHV-72) representing an isolate of mouse
      herpesvirus strain 68 (MHV-68, species Murid herpesvirus 4, genus Rhadinovirus,
      subfamily Gammaherpesvirinae, family Herpesviridae) (van Regenmortel et al.,
      2000). In acute infection (up to day 30 post infection (p.i.)) the number of CD8+
      T cells increased, reaching a maximum at day 11 p.i. This increase correlated
      with that of CD4+ T, activated CD 19+ B and natural killer (NK) cells. At day 30
      p.i. the numbers of CD4+, CD8+, CD14+ and CD19+ cells decreased to normal values.
      A similar increase in the number of these cells was observed at day 730 p. i. In
      the course of persistent infection (after day 30 p.i.) some of the mice developed
      a leukemia-like syndrome characterized by an increase in the number of leukocytes
      and appearance of atypical, blastic immature forms of leukocytes. The latter
      forms of leukocytes were characteristic by an increased amount of argyrophilic
      proteins. These results show further similarities between MHV-72 (another isolate
      of MHV-68) and EBV infections and justify the use of MHV-68 or MHV-72 as an
      appropriate mouse model for the study of EBV infection of humans.

PMID- 12197631
TI  - Determination of genome size and restriction fragment length polymorphism of four
      Chinese rickettsial isolates by pulsed-field gel electrophoresis.
AB  - Pulsed-field gel electrophoresis (PFGE) was used to determine the genome size and
      the restriction fragment length polymorphism (RFLP) of four new Chinese isolates
      of spotted fever group (SFG) rickettsiae. The genome size of the isolates Ha-91,
      BJ-90, 054 and 036 was 1,253 kb, 1,236 kb, 1,272 kb, and 1,272 kb, respectively.
      The isolates 054 and 036 had identical RFLP profiles. All the isolates differed
      in the properties under study from the so far known SFG rickettsiae. The unique
      RFLP profiles of the isolates supported our opinion that they are new strains of
      SFG rickettsiae or even new species of SFG rickettsiae.

PMID- 12197632
TI  - Creutzfeldt-Jakob disease with E200K mutation in Slovakia: characterization and
      development.
AB  - Creutzfeldt-Jakob disease (CJD), the most important human prion disease, occurs
      in sporadic, iatrogenic and familial form. Except Slovakia and Israel, the
      recorded familial cases have never exceeded 10-15%. In the Slovak CJD group 95
      out of 136 CJD cases (74.2%) carried a CJD-specific mutation in the prion protein
      gene (PRNP) at codon 200 (mutation E200K). All CJD(E200K) patients carried a
      heterozygous E200K mutation within the alelle with methionine at codon 129. No
      more than 53.7% were typical familial cases. The penetrance of the E200K mutation
      in 1975-2000 was 59.5%. The distribution of codon 129 polymorphism showed 78.6%
      of methionine-homozygous and 21.4% of methionine/valine-heterozygous patients.
      Genetic analysis performed on 278 CJD patient relatives demonstrated the E200K
      mutation in 97 (34.8%) of healthy relatives tested. The E200K mutation carriers
      were methionine-homozygous in 64% and methionine/valine-heterozygous in 36%. The
      relatives without the mutation showed a 54.9% methionine homozygosity, 10.4%
      valine homozygosity and 34.7% methionine/valine heterozygosity. Analysis ofthe
      E200K carriers provided evidence that the methionine homozygosity is a CJD risk
      factor, more efficient in CJD patients than in asymptomatic relatives. Th
      influence of both the E200K mutation and methionine homozygosity at codon 129 was
      evident in the duration of the clinical stage of CJD and in the immunoreactivity
      pattern of PrP resistant to proteases (PrP(res)). In the CJD(E200K) methionine
      homozygous patients the mean duration ofthe disease was significantly shorter
      (3.7 +/- 2.0 months) than in the methionine/valine-heterozygous patients (7.84 +/
      7.3 months). Comparison of the PrP(res) positivity in the cerebellum of familial
      and sporadic CJD using specific polyclonal and monoclonal antibodies (MAbs) to
      PrP showed less conspicuous immune reaction in CJD(E200K) cases. Methionine
      homozygous CJD patients were characteristic mainly by synaptic pattern of
      staining, while methionine/valine-heterozygous patients by PrP(res) granules and
      plaque-like structures. Most of numerous plaque-like PrP(res) deposits were found
      in sporadic valine/valine-homozygous cases. Potential professional risk was
      excluded in health facility workers. The percentage of professions related to
      farming was significantly higher in CJD(E200K) (48%) and sporadic CJD (44%) cases
      as compared to the employed population (9%).

PMID- 12197633
TI  - Pathogenetic characterization of a mouse herpesvirus isolate Sumava.
AB  - BALB/c mice inoculated intranasally (i.n.) with the mouse herpesvirus isolate
      Sumava (MHV-Sumava) did not show apparent symptoms of illness. However, they
      showed an increase in the number of leukocytes and appearance of atypical
      leukocytes in peripheral blood. The infiltration of spleen with atypical cells
      resulted in splenomegaly. In the course of the infection the virus persisted in
      lungs, spleen, thymus, bone marrow, mammary glands, peritoneal macrophages and
      liver. We regard MHV-Sumava as one of the eight isolates of MHV-68 (a virus and
      species Murid herpesvirus 4, genus Rhadinovirus, subfamily Gammaherpesvirinae,
      family Herpesviridae (van Regenmortel et al., 2000)) so far obtained. MHV-Sumava
      differs from MHV-68, MHV-72 and MHV-76 in some virological and pathogenetical
      features.

PMID- 12197634
TI  - Evaluation of anew rapid whole-blood serological test for hepatitis c virus.

PMID- 12197635
TI  - Agents of Ehrlichia phagocytophila group and other microorganisms co-infecting
      ticks in southwestern Slovakia.

PMID- 12197636
TI  - Effect of anticoagulants on the susceptibility of Aedes aegypti mosquitoes to
      dengue virus infection.

PMID- 12197637
TI  - Parameters affecting partitioning of 6 PCB congeners in natural sediments.
AB  - Polychlorinated biphenyls (PCBs) released by bottom sediments were determined by
      experiments in which the sediments were artificially resuspended using sediment
      contaminated with PCBs in a particle entrainment simulator (PES). Sediment cores,
      spiked with PCBs, were collected from the Housatonic River in Connecticut and run
      in the PES at simulated shear stresses from 0 to 0.6 N m(-2). Experimental
      results from these simulations have shown that mean concentration of PCBs in the
      solid phase for sites with high volatile organic carbon (VOC) were significantly
      greater than samples with low VOC; the reverse was true for the water phase. In
      addition, on a mass load basis, the amount of PCBs found in sediment increased
      when shear stresses were increased from 0 to 0.6 N m(-2), beyond which shear
      stress did not affect mass loads in the water column. Partition coefficients (Kp)
      were determined from PES sediment and water data for the following congeners: PCB
      28, PCB 52, PCB 101, PCB 138, PCB 153, PCB 180. Kp was determined to be inversely
      proportional to total suspended solids (TSS), but directly proportional to
      chlorine content of the congener. Because of the strong influence of TSS and VOC
      concentrations on Kp values, agitation of samples using a PES better simulated
      real environmental conditions when compared to jar studies where no agitation was
      employed. Therefore, a device like the PES is more appropriate in obtaining Kp
      that would be found under real stream flow conditions when compared to the
      traditional way of measuring Kp using the jar study technique.

PMID- 12197639
TI  - The impact of handpump corrosion on water quality in rural areas of West African
      sub-region.
AB  - Water, even in its natural environment, contains some level of impurities. Water
      is nearly a universal solvent. It contains dissolved solids and gases, and hosts
      a number of micro-organisms. The exploitation of groundwater by means of
      boreholes for supplying small user groups and rural communities with water has
      been widely applied in certain parts of the world for several decades. In recent
      years this practice has spread all over the globe, and hundred of thousands of
      boreholes have been drilled to tap low-yield aquifers. It is evident that such
      boreholes require pumps for lifting the water. In developing countries these are
      usually handpumps, but solar as well as other systems with submersible pumps are
      also used, depending upon the energy sources available and the financial means of
      the beneficiaries. This article gives a general overview of groundwater quality
      with regard to its physico-chemical composition. The results presented originate
      from the experience gained from handpump equipped boreholes within the UNICEF
      through German Centre for Technical Education Transfer executed inter-regional
      UNDP-Handpumps Project in West African Regions. Particular attention is paid to
      presenting corrosion on the water quality of wells in terms of iron concentration
      and other parameters. Furthermore, the corrosion attack on galvanised iron, the
      effect of biofilms on the corrosion rate, and the difference between internal and
      external corrosion of rising mains are shown.

PMID- 12197638
TI  - Influence of aluminium on the restoration potential of a terrestrial vascular
      plant, Portulaca Oleracea L. as a biomonitoring tool of fresh water aquatic
      environments.
AB  - In the present study, the influence of aluminium on the regeneration potential of
      leaf and stem-cuttings of Portulaca oleracea was studied in order to identify a
      terrestrial plant species as an alternate biomonitoring tool of fresh water
      environment. The leaves and stem cuttings of the terrestrial plant, P. oleracea
      grew well in the distilled water producing adventitious and lateral roots. The
      aluminium treated leaves and stem cuttings showed a reduction in the growth of
      the adventitious and lateral roots and increase in the decay of leaves and stem
      cuttings with increasing aluminium concentration. The tolerance index calculated
      for the leaves and the stem cuttings showed that the leaves were more sensitive
      than stems to aluminium. Since all the parameters studied showed concentration
      dependent changes, the terrestrial plant, P oleracea can be considered a suitable
      'biomonitoring tool' of fresh water environment besides its usage in the Al
      toxicity testing.

PMID- 12197640
TI  - Selecting indicator species to monitor ecological integrity: a review.
AB  - We review critical issues that must be considered when selecting indicator
      species for a monitoring program that aims to maintain or restore ecological
      integrity. First, we examine the pros and cons of different management approaches
      on which a conservation program can be based and conclude that ecosystem
      management is most appropriate. We then identify potential indicators of
      ecological integrity at various levels of the ecosystem, with a particular
      emphasis on the species level. We conclude that, although the use of indicator
      species remains contentious, it can be useful if (1) many species representing
      various taxa and life histories are included in the monitoring program, (2) their
      selection is primarily based on a sound quantitative database from the focal
      region, and (3) caution is applied when interpreting their population trends to
      distinguish actual signals from variations that may be unrelated to the
      deterioration of ecological integrity. Finally, we present and discuss different
      methods that have been used to select indicator species.

PMID- 12197641
TI  - Joint versus separate estimation of state and change in category frequencies from
      repeat stratified two-phase sampling with a fallible classifier.
AB  - Joint maximum likelihood estimates (JML) of category frequencies and change from
      repeat stratified two-phase sampling surveys with a fallible classifier are often
      seriously biased and have large root mean square errors when they are obtained
      for small populations (<5,000) with three or more categories and a moderate to
      small phase II sample size (<1,000). JML estimates of state also depend on
      antecedent or posterior data, a recipe for inconsistency. In these situations, a
      separate maximum likelihood estimation (SML) of category frequencies at each
      survey date appears preferable. SML estimates of net change are obtained as the
      difference in states. SML standard errors of change are obtained via an estimate
      of the temporal correlation and variances of state. A bivariate binary logistic
      model of change provided the estimate of temporal correlation. SML generally
      outperformed JML significantly in terms of bias and root mean square errors in
      eight case studies.

PMID- 12197643
TI  - Optical generation of fuzzy-based rules.
AB  - In the last third of the 20th century, fuzzy logic has risen from a mathematical
      concept to an applicable approach in soft computing. Today, fuzzy logic is used
      in control systems for various applications, such as washing machines, train
      brake systems, automobile automatic gear, and so forth. The approach of optical
      implementation of fuzzy inferencing was given by the authors in previous papers,
      giving an extra emphasis to applications with two dominant inputs. In this paper
      the authors introduce a real-time optical rule generator for the dual-input fuzzy
      inference engine. The paper briefly goes over the dual-input optical
      implementation of fuzzy-logic inferencing. Then, the concept of constructing a
      set of rules from given data is discussed. Next, the authors show ways to
      implement this procedure optically. The discussion is accompanied by an example
      that illustrates the transformation from raw data into fuzzy set rules.

PMID- 12197642
TI  - Dissolved oxygen content as an index of water quality in San Vicente Bay, Chile
      (36 degrees 45'S).
AB  - The present report describes some effects of industrial and municipal effluents
      on the waters of San Vicente Bay. Analyses of the main substances contained in
      the fishing industry effluent suggest rating criteria based on the oxygen
      saturation of the water as an assessment of organic pollution. Six cruises were
      carried out throughout the Bay, from June to December 1996. Water samples were
      analyzed for dissolved oxygen, oil and grease content, and sediment samples for
      organic matter content. Water parameters (salinity, temperature) were used to
      characterize the Bay's hydrography, and to calculate values for oxygen
      saturation. The measurements demonstrated a local broad range of oxygen deficit,
      with a maximum of 45% in the winter to 95% in the spring. In November more than
      65% of the Bay's area showed oxygen deficits greater than 40%. Organic matter was
      unusually high in sediments along the northern sector of the Bay. The results
      suggest that the oxygen depletion was a representative parameter for establishing
      a relative scale of water quality in this Bay.

PMID- 12197644
TI  - Recognition of cuneiform inscription signs by use of a hybrid-optoelectronic
      correlator device.
AB  - A hybrid-optoelectronic correlator device and an algorithm are proposed for
      recognizing cuneiform inscription signs. The device is based on the extended
      correlator architecture with three liquid-crystal display(s) (LCD)s and three
      light detectors: one CCD camera for capturing the input image, oneLCD for
      displaying the input image, two LCDs for the complex correlation filter
      (amplitude and phase parts), and two detectors for measuring the total and peak
      intensities of the output correlation information. The recognition algorithm is
      designed to allow automatic as well as real-time processing. The recognition
      results are given for the cuneiform signs impressed on an original clay tablet.
      The investigated tablet (VAT 12890 of the Pergamon Museum, Berlin, Germany) was
      found in Bogazkoy (Hattusha) and dates from the 14th century B.C. It is a
      fragment of the Epic of Gilgamesh in the Akkadian language with a large number of
      the sign samples.

PMID- 12197645
TI  - Short-range synthetic aperture imaging at 633 nm by digital holography.
AB  - We present an active optical synthetic aperture-imaging system. A phase-step
      digital holographic setup is used as a wavefront sensor in the far field. The
      overlap of the holograms enables the estimation and compensation of their
      relative positions and phase with a speckle cross-correlation algorithm.
      Experimental results on a short-range synthetic aperture setup at 633 nm are
      presented that are based on 128 x 128 holograms. The synthesis is executed in one
      direction by means of rotation of the object. Test images show a significant gain
      of resolution in the synthesis direction. Processing errors are estimated through
      experiment. Random processing errors of a synthetic pupil composed of 33 merged
      holograms are negligible, but biases induced by unknown optical aberrations ofthe
      reference wave induce defocusing and astigmatism.

PMID- 12197646
TI  - Assessment of the Wiener-Retinex process.
AB  - We assess the performance of the Retinex transformation, the Wiener restoration,
      and the combined Wiener-Retinex process in the context of the end-to-end model of
      color visual-communication channels for near-surface acquisition. We extend the
      formulations of panchromatic imaging for the nonlinear Retinex transformation and
      the linear Wiener and Wiener-Retinex restoration filters to color imaging. We
      further assess the accuracy by which colors are restored in the cases of uniform
      and spatially varying irradiance levels, and the shadow depth for which color
      consistency is still possible with reasonable accuracy. Finally, we assess the
      sensitivity of these processes to perturbations in the visual channel, including
      the image-gathering design and the spatial support of the Retinex transformation.

PMID- 12197647
TI  - Digital restoration of defocused images in the wavelet domain.
AB  - Many cameras nowadays are equipped with an autofocus mechanism that attempts to
      take pictures at the best possible focus. However, there are situations in which
      the pictures are still out of focus, such as when the photographer has mistakenly
      focused at a wrong position or when the focusing region consists of objects of
      different depths and therefore confuses the autofocus system. With a digital
      camera, we can attempt to use digital image-restoration techniques to bring the
      pictures back into focus. We design an algorithm that restores the image by
      digitally enhancing the corresponding frequency bands. We employ the restoration
      in the wavelet domain so that this restoration scheme can be compliant with JPEG
      2000, which is positioned to succeed JPEG as the next image-compression standard
      and has the potential to be widely adopted by the digital photography industry
      owing to its many advanced features.

PMID- 12197648
TI  - Parallel image restoration with a two-dimensional likelihood-based algorithm.
AB  - We describe a pixelwise parallel algorithm for the restoration of images that
      have been corrupted by a low-pass optical channel and additive noise. This new
      algorithm is based on an iterative soft-decision method of error correction
      (i.e., turbo decoding) and offers performance on binary-valued imagery that is
      comparable to the Viterbi algorithm. We quantify the restoration performance of
      this new algorithm on random binary imagery for which it is superior to both the
      Wiener filter and the projection onto convex sets algorithms over a wide range of
      channels. For typical optical channels, the new algorithm is within 0.5 dB of the
      two-dimensional Viterbi restoration method [J. Opt. Soc. Am. A 17, 265 (2000)].
      We also demonstrate the extension of our new algorithm to correlated and gray
      scale images using vector quantization to mitigate the associated complexity
      burden. A highly parallel focal-plane implementation is also discussed, and a
      design study is presented to quantify the capabilities of such a VLSI hardware
      solution. We find that video-rate restoration on 252 x 252 pixel images is
      possible using current technology.

PMID- 12197649
TI  - Multiple-phase retrieval for optical security systems by use of random-phase
      encoding.
AB  - The technique of the multiple phase encoding for optical security and
      verification systems is presented in this paper. This technique is based on a 4-f
      optical correlator that is a common architecture for optical image encryption and
      verification systems. However, two or more phase masks are iteratively retrieved
      by use of the proposed multiple phases retrieval algorithm (MPRA) to obtain the
      target image. The convergent speed of the iteration process in the MPRA is
      significantly increased and the recovered image is much more similar to the
      target image than those in previous approaches. In addition, the quantization
      effects due to the finite resolution of the phase levels in practical
      implementation are discussed. The relationships between the number of phase masks
      and the quantized phase levels are also investigated. According to the simulation
      results, two and three phase masks are enough to design an efficient security
      verification system with 64 and 32 phase levels, respectively.

PMID- 12197650
TI  - Selective edge enhancement of images with an acousto-optic light modulator.
AB  - We show experimental results for image processing using an acousto-optic light
      modulator (AOLM) where the image can be edge enhanced with respect to the input
      object. We can select which edges are enhanced and the degree to which they are
      enhanced by changing the amplitude of the acoustic wave of the AOLM. We relate
      this technique to the fractional Hilbert transform and the fractional derivative
      image-processing operations and discuss its application to phase-only input
      images.

PMID- 12197651
TI  - Nonlinear estimation of spectral reflectance based on Gaussian mixture
      distribution for color image reproduction.
AB  - Nonlinear estimation method of spectral reflectance from camera responses is
      proposed. The proposed method minimizes the mean square error of spectral
      reflectance when the reflectance can be regarded as a random sequence of Gaussian
      mixture distribution. In computer simulations, 168 samples of spectral
      reflectance from a color chart are estimated from their image signals obtained by
      three- and six-band cameras. It is confirmed that the proposed method improves
      the accuracy in comparison with the conventional Wiener estimation method.

PMID- 12197652
TI  - Practical image encryption and decryption by phase-coding technique for optical
      security systems.
AB  - A method of image encryption and decryption is proposed for optical security
      systems. A phase-coded image to be encrypted together with a random phase pattern
      is Fourier transformed and the result of the complex-valued data is used as an
      encrypted pattern. The decryption is simply performed by an inverse-Fourier
      transform for the addition of the encrypted pattern and the Fourier transform of
      the random phase. The intensity of the inverse-Fourier transformed image gives
      the exact result forthe decryption. Further, the binarization of the encrypted
      pattern is performed for the easiness of the optical and electronic readout of
      the images, and it also gives rise to the enhancement of the degree of security
      for the encryption. The binary pattern is optimized by a statistical iteration
      technique and an excellent decryption image is obtained by the optimization.

PMID- 12197653
TI  - Theoretical analysis for three-dimensional integral imaging systems with double
      devices.
AB  - By adoption of double-device systems, integral imaging can be enhanced in image
      depth, viewing angle, or image size. Theoretical analyses are done for the double
      image-plane integral imaging systems. Both ray optics analysis and wave optics
      analysis confirm that the double-device integral imaging systems can pick up and
      display images at two separate image planes. The analysis results are also
      valuable in the understanding of the conventional integral imaging systems for
      image positions off the central depth plane.

PMID- 12197654
TI  - Real-time all-optical three-dimensional integral imaging projector.
AB  - We present an all-optical three-dimensional integral imaging projector. An
      optically addressed spatial-light modulator is used, which potentially provides
      better image resolution than the conventional CCD and liquid-crystal display
      pair. We present experimental results using a liquid-crystal light valve.

PMID- 12197655
TI  - New method for thermo-optical modeling in liquid crystals.
AB  - To investigate the thermo-optical effect in liquid crystal(s) (LC)s the
      statistical methods of experiment planning are applied. The experiment was
      conducted in accordance with the technique of orthogonal central compositional
      planning. In the course of the experiment, physical parameters (scanning
      velocity, laser beam intensity, LC temperature) have been varied on five levels.
      The obtained mathematical model describes the dependence of light-scattering
      texture dimensions in the LC layer onphysical parameters of information by thermo
      optical registration. Such a model allows us to determine the suitable function
      model to obtain the preset dimensions of the light-scattering texture in a LC
      layer.

PMID- 12197656
TI  - Fast surface profiler by white-light interferometry by use of a new algorithm
      based on sampling theory.
AB  - We propose a fast surface-profiling algorithm based on white-light interferometry
      by use of sampling theory. We first provide a generalized sampling theorem that
      reconstructs the squared-envelope function of the white-light interferogram from
      sampled values of the interferogram and then propose the new algorithm based on
      the theorem. The algorithm extends the sampling interval to 1.425 microm when an
      optical filter with a center wavelength of 600 nm and a bandwidth of 60 nm is
      used. The sampling interval is 6-14 times wider than those used in conventional
      systems. The algorithm has been installed in a commercial system that achieved
      the world's fastest scanning speed of 80 microm/s. The height resolution of the
      system is of the order of 10 nm for a measurement range of greater than 100
      microm.

PMID- 12197657
TI  - Effect of wave-number error on the computation of path-length delay in white
      light interferometry.
AB  - We analyze the error in computed optical path-length delay when using a phase
      shifting interferometry (PSI) algorithm with an error in the operating
      wavelength. The delay error decomposes into two terms. The first is the error in
      the conversion from a phase measurement to the delay because of the incorrect
      wavelength, and the second is the error made in the phase measurement itself that
      is due to the wavelength error. The most important aspect of this investigation
      is to ascertain this latter error. A general characterization is obtained, and a
      particularly simple formula is developed for the special case of least-squares
      estimation involving only the ratio of the wave-number error to the wave number
      and a multiplicative factor that is an a priori computable nonlinear function of
      the ratio of the modulator stroke length to the operating wavelength. Because the
      ultimate path-length error is a function of the two terms, a new set of PSI
      algorithms that compensate the computed phase error to cancel the conversion
      error is developed. Numerical simulations are presented to validate the analysis
      and establish the insensitivity of the new algorithms to wave-number error.

PMID- 12197658
TI  - Two-color photorefractive effect in Mg-doped lithium niobate.
AB  - The two-color photorefractive response of near stoichiometric lithium niobate
      (SLN) doped with Mg above a critical threshold has been investigated. Striking
      differences as compared with non Mg-doped material were observed: The
      intermediate level in the two-color writing process has approximately a two
      orders of magnitude longer lifetime in SLN:Mg than in nominally undoped SLN, the
      grating is written in a shallower level but can be fixed via a simple thermal
      process and complementary electron-hole gratings are formed. It is proposed that
      the Fe impurity level moves from below the small-polaron level in nonMgO-doped
      material to above it, resulting in the increased lifetime of the small polaron.
      These changes are associated with a shift of the Fe from a Li site to a Nb site.
      The two-color sensitivity is higher than in the absence of MgO but the dynamic
      range is much lower.

PMID- 12197659
TI  - Efficient computation of optical disk readout by use of the chirp z transform.
AB  - Computation of the readout signal of an optical disk involves Fourier transforms
      from the objective lens pupil to the disk and, after interaction with the disk,
      from the disk to the objective pupil. Traditionally, the complex two-dimensional
      Fourier transform is numerically evaluated as a two-dimensional fast Fourier
      transform. To obtain sufficient resolution in the involved planes, one must
      choose sampling grid sizes of typically 1,024 x 1,024 or higher, resulting in a
      substantial computation time if the calculation is to be repeated many times.
      Discussed is an alternative method for evaluating the Fourier transform, based on
      the chirp z transform, by which a considerable improvement in efficiency can be
      obtained without loss of accuracy.

PMID- 12197660
TI  - Adaptive beam steering implemented in a ferroelectric liquid-crystal spatial
      light-modulator free-space, fiber-optic switch.
AB  - Active alignment of a 1 x 8 free-space optical switch was studied experimentally.
      Optical signals, carried on single-mode fibers, were switched by a ferroelectric
      liquid-crystal-on-silicon spatial light modulator. Continuous measurement of the
      in-coupled power to the fibers provided feedback for the switch control. The
      switch automatically located and locked to the output fibers. An advantage with
      adaptive switches of a similar kind is relaxed geometrical tolerances in the
      switch assembly. Further, such switches can adapt to possible geometrical changes
      and light wavelength drift during operation.

PMID- 12197661
TI  - Optical true time delay for phased-array antennas: demonstration of a quadratic
      White cell.
AB  - We have demonstrated a proof-of-concept optical device that can produce true time
      delays for a phased-array radar. This device combines White cells of differing
      lengths with a spatial light modulator to select between the paths on multiple
      bounces of a given beam. The approach can handle thousands of light beams and
      produce hundreds of different delays. The number of delays is proportional to the
      square of the number of bounces.

PMID- 12197662
TI  - 3D hydrogen bond thermodynamics (HYBOT) potentials in molecular modelling.
AB  - A new approach is proposed to more accurately estimate the energies of H-bond
      interactions in three-dimensional (3D) molecular modelling. The approach is based
      on the use of H-bond acceptor and donor enthalpy factor values calculated by
      means of program HYBOT, the use of a sigmoid relationship to determine the
      optimum H-bond distances and established force-field methods to determine
      distance and angle dependencies. The base-pair interactions in a short A-form RNA
      double-helix are presented as an example of enthalpy calculations of hydrogen
      bonding for a model system.

PMID- 12197663
TI  - Further development and validation of empirical scoring functions for structure
      based binding affinity prediction.
AB  - New empirical scoring functions have been developed to estimate the binding
      affinity of a given protein-ligand complex with known three-dimensional
      structure. These scoring functions include terms accounting for van der Waals
      interaction, hydrogen bonding, deformation penalty, and hydrophobic effect. A
      special feature is that three different algorithms have been implemented to
      calculate the hydrophobic effect term, which results in three parallel scoring
      functions. All three scoring functions are calibrated through multivariate
      regression analysis of a set of 200 protein-ligand complexes and they reproduce
      the binding free energies of the entire training set with standard deviations of
      2.2 kcal/mol, 2.1 kcal/mol, and 2.0 kcal/mol, respectively. These three scoring
      functions are further combined into a consensus scoring function, X-CSCORE. When
      tested on an independent set of 30 protein-ligand complexes. X-CSCORE is able to
      predict their binding free energies with a standard deviation of 2.2 kcal/mol.
      The potential application of X-CSCORE to molecular docking is also investigated.
      Our results show that this consensus scoring function improves the docking
      accuracy considerably when compared to the conventional force field computation
      used for molecular docking.

PMID- 12197664
TI  - Molecular docking studies of a group of hydroxamate inhibitors with gelatinase-A
      by molecular dynamics.
AB  - We have performed docking and molecular dynamics simulations of hydroxamates
      complexed with human gelatinase-A (MMP-2) to gain insight into the structural and
      energetic preferences of these inhibitors. The study was conducted on a selected
      set of eleven compounds with variation in structure and activity. Molecular
      dynamics simulations were performed at 300 K for 100 ps with equilibration for 50
      ps. The structural analyses of the trajectories indicate that the coordinate bond
      interactions, the hydrogen bond interactions, the van der Waals interactions as
      well as the hydrophobic interactions between ligand and receptor are responsible
      simultaneously for the preference of inhibition and potency. The ligand
      hydroxamate group is coordinated to the catalytic zinc ion and form stable
      hydrogen bonds with the carbonyl oxygen of Gly 162. The P1' group makes extensive
      van der Waals and hydrophobic contacts with the nonpolar side chains of several
      residues in the S1' subsite, including Leu 197, Val 198, Leu 218 and Tyr 223.
      Moreover, four to eight hydrogen bonds between hydroxamates and MMP-2 are formed
      to stabilize the inhibitors in the active site. Compared with the P2' and P3'
      groups, the P1' groups of inhibitors are oriented regularly, which is produced by
      the restrain of the S1' subsite. From the relationship between the length of the
      nonpolar P1' group and the biological activity, we confirm that MMP-2 has a
      pocket-like S1' subsite, not a channel-like S1' subsite proposed by Kiyama
      (Kiyama, R. et al., J. Med. Chem. 42 (1999), 1723). The energetic analyses show
      that the experimental binding free energies can be well correlated with the
      interactions between the inhibitors and their environments, which could be used
      as a simple score function to evaluate the binding affinities for other similar
      hydroxamates. The validity of the force field parameters and the MD simulations
      can be fully testified by the satisfactory agreements between the experimental
      structure-activity relationship and the information from the structural and
      energetic analyses. The information generated from the predicted complexes should
      be useful for further work in the area of structure-based design of new
      compounds.

PMID- 12197665
TI  - Q-fit: a probabilistic method for docking molecular fragments by sampling low
      energy conformational space.
AB  - A new method is presented that docks molecular fragments to a rigid protein
      receptor. It uses a probabilistic procedure based on statistical thermodynamic
      principles to place ligand atom triplets at the lowest energy sites. The
      probabilistic method ranks receptor binding modes so that the lowest energy ones
      are sampled first. This allows constraints to be introduced to limit the depth of
      the search leading to a computationally efficient method of sampling low energy
      conformational space. This is combined with energy minimization of the initial
      fragment placement to arrive at a low energy conformation for the molecular
      fragment. Two different search methods are tested involving (i) geometric hashing
      and (ii) pose clustering methods. Ten molecular fragments were docked that have
      commonly been used to test docking methods. The success rate was 8/10 and 10/10
      for generating a close solution ranked first using the two different sampling
      procedures. In general, all five of the top ranked solutions reproduce the
      observed binding mode, which increases confidence in the predictions. A set of
      ten molecular fragments that have previously been identified as problematic were
      docked. Success was achieved in 3/10 and 4/10 using the two different methods.
      Again there is a high level of agreement between the two methods and again in the
      successful cases the top ranked solutions are correct whilst in the case of the
      failures none are. The geometric hashing and pose clustering methods are fast
      averaging approximately 13 and approximately 11 s per placement respectively
      using conservative parameters. The results are very encouraging and will
      facilitate the process of finding novel small molecule lead compounds by virtual
      screening of chemical databases.

PMID- 12197666
TI  - Effectiveness of graph-based and fingerprint-based similarity measures for
      virtual screening of 2D chemical structure databases.
AB  - This paper reports an evaluation of both graph-based and fingerprint-based
      measures of structural similarity, when used for virtual screening of sets of 2D
      molecules drawn from the MDDR and ID Alert databases. The graph-based measures
      employ a new maximum common edge subgraph isomorphism algorithm, called RASCAL,
      with several similarity coefficients described previously for quantifying the
      similarity between pairs of graphs. The effectiveness of these graph-based
      searches is compared with that resulting from similarity searches using BCI,
      Daylight and Unity 2D fingerprints. Our results suggest that graph-based
      approaches provide an effective complement to existing fingerprint-based
      approaches to virtual screening.

PMID- 12197667
TI  - Distribution and enzyme histochemical characterisation of mast cells in cats.
AB  - Mast cells from 15 different cat organs were examined in terms of distribution
      and protease activity. The number of mast cells in each site was found to vary
      when visualised by metachromatic staining using Alcian Blue. Enzyme histochemical
      analysis revealed the existence of two subtypes of mast cells. These were
      categorised based on protease content, i.e. whether the mast cells contained
      chymase or tryptase. Tryptase-positive mast cells were clearly identifiable in
      every organ examined, whereas chymase-containing mast cells were predominantly
      observed in the ear (skin), tongue, spleen, and submucosa of the stomach and
      rectum. The chymase-reactive cells were not detected in the heart, or in the
      muscularis or serosa of the duodenum, jejunum, ileum or rectum. In addition, we
      suggest the existence of another subtype of mast cell containing both chymase and
      tryptase and localised within the ear (skin), tongue, spleen and submucosa of the
      rectum.

PMID- 12197668
TI  - Increased density of glutamate receptor subunit 1 due to Cerebrolysin treatment:
      an immunohistochemical study on aged rats.
AB  - Glutamate receptor subunit 1 (GluR1) is one of the four possible subunits of the
      AMPA-type glutamate receptor. The integrity of this receptor is crucial for
      learning processes. However, reductions of GluR1 are noticeable in the
      hippocampal formation of patients suffering from Alzheimer's disease. Such
      degradations presumably result in an impaired synaptic communication and might be
      causally linked to the neurodegenerative process in this cognitive disorder. The
      peptidergic drug Cerebrolysin counteracts cognitive deficits of patients affected
      by Alzheimer's disease. These findings are supported by experiments revealing
      neuroprotective and neurotrophic capacities of the drug. In order to examine the
      effect of the drug on the density of GluR1 in hippocampal formation 24-month-old
      rats were treated with either Cerebrolysin or its peptide fraction E021, or
      saline as a control. Spatial navigation of the animals was tested in the Morris
      water maze. Rat brain slices were stained immunohistochemically with a GluR1
      specific antibody. GluR1 immunoreactivity was quantified using light microscopy
      and a computerised image analysis system. Cerebrolysin and E021 increased GluR1
      density in most measured regions of the hippocampal formation in a highly
      significant way. These results correlate with the behavioural outcome, revealing
      an improvement in learning and memory of these rats after treatment with
      Cerebrolysin and E021.

PMID- 12197669
TI  - Immunolocalization of centriole-associated striated rootlets in human
      submandibular gland cells with and without solitary cilia.
AB  - Using an antibody specific to striated rootlets, we investigated the
      immuolocalization of striated rootlets in cells constituting human submandibular
      glands. Striated rootlets were positively stained in all cell types constituting
      acini, intercalated ducts, striated ducts, and interlobular ducts, but their
      shapes were different. The mean lengths of striated rootlets were 1.46 +/- 0.49,
      3.15 +/- 1.35 and 3.99 +/- 1.02 microm in acinar secretory cells, myoepithelial
      cells, and columnar cells of the striated duct, respectively. The rootlets were
      the longest in columnar cells of the striated duct, in which paired centrioles
      were located in the apical cytoplasm away from nuclei. These findings suggest
      that striated rootlets play important roles in the positioning of centrioles in
      the cell. 2-8% of striated rootlets in myoepithelial cells were associated with
      solitary cilia, but they were not associated with solitary cilia in acinar cells
      and columnar cells of the striated duct. These observations suggest that striated
      rootlets may be associated with centrioles under normal physiological conditions,
      without formation of solitary cilia.

PMID- 12197670
TI  - The renal expression of heat shock protein 47 and collagens in acute and chronic
      experimental diabetes in rats.
AB  - Glomerulosclerosis and tubulointerstitial fibrosis are the main structural
      changes found in the later stages of diabetic nephropathy, which is clinically
      characterized by proteinuria, and progressive renal insufficiency. Heat shock
      protein (HSP) 47, a collagen-binding stress protein, has a specific role in the
      intracellular processing of procollagen molecules during collagen synthesis. It
      is implicated in the pathogenesis of various fibrotic diseases. However, the
      expression and significance of HSP47 in acute and chronic phases of diabetic
      nephropathy is not yet known. In this study, we studied the expression of HSP47
      in the kidneys obtained from streptozotocin-induced diabetic rats, in both short-
      and long-term diabetes. To determine the renal expression of HSP47, and collagens
      (type III and IV) in acute (days 1, 3 and 14) and chronic (weeks 4, 12 and 24)
      diabetes, we have performed a time-course study using streptozotocin-induced
      diabetic rats. The expression pattern of alpha-smooth muscle actin (to identify
      mesangial cell damage), vimentin (to identify tubular epithelial cell damage),
      and desmin (to identify glomerular epithelial cell damage) was also determined in
      kidneys of these diabetic rats. Antibodies specific for HSP47, type III and type
      IV collagens, alpha-smooth muscle actin, vimentin, and desmin were used to assess
      the relative expression of their proteins in paraffin-embedded kidney sections by
      immunohistochemistry. Compared to control rat kidneys, no significant changes in
      the expression of HSP47 was found in the kidneys of acute diabetic rats. However
      a significant increase in the expression of HSP47 was noted in the kidneys of
      chronic diabetic rats; increased expression of HSP47 correlated with an increased
      renal deposition of types III and IV collagens. Similarly, compared to kidneys of
      control and acute diabetic rats, an increased expression of alpha-smooth muscle
      actin (in mesangial cells), vimentin (in tubular epithelial cells), and desmin
      (in glomerular epithelial cells) was detected in the kidneys of chronic diabetic
      rats; by dual immunostaining, these phenotypically-altered renal cells in kidneys
      of chronic diabetic rats were found to be HSP47-producing cells. Importantly,
      HSP47 up-regulation coincided with the initiation and progression of renal
      fibrosis, as determined by the expression and deposition of collagens. Our
      results strongly support a pathological role for HSP47 in the later stages
      (sclerotic phase) of streptozotocin-induced diabetic nephropathy, which is
      associated with glomerulosclerosis and tubulointerstitial fibrosis.

PMID- 12197671
TI  - Immunohistochemical distribution of laminin-5 gamma2 chain and its developmental
      change in human embryonic and foetal tissues.
AB  - Immunohistochemical distribution of laminin gamma2 chain, a subunit of the
      basement membrane protein laminin-5, was examined in 19 cases of human embryos
      and foetuses ranging from 4 to 25 weeks of gestation. Laminin gamma2 was first
      detected in the basement membranes underlying ectodermal epithelial tissues, such
      as the skin and tooth, as early as 5-6 weeks of gestation. Between 6-7 and 12-13
      weeks, laminin gamma2 was detected in the basement membranes of various
      endodermal epithelial tissues, such as the bronchus, oesophagus, stomach,
      intestines, urinary bladder, gallbladder and hepatopancreatic duct. The
      deposition of laminin gamma2 in basement membrane was associated with the process
      of morphogenesis. In the small intestine, laminin gamma2 first appeared in the
      basement membrane of the primitive short villi, and its level gradually increased
      in the villus region but decreased in the cryptic region during the maturation of
      the organ. In addition, non-basement membrane immunoreactivity for laminin gamma2
      was detected in some mesoderm-derived tissues, such as the cartilage and skeletal
      and smooth muscle fibres. These results suggest a common role of laminin-5 and
      some specific roles of its gamma2 chain in the morphogenesis of human tissues.

PMID- 12197672
TI  - Vasoactive intestinal peptide stimulation modulates the expression of Bcl-2
      family members in the adrenal gland of the lizard Podarcis sicula.
AB  - The adrenal gland of the lizard Podarcis sicula is formed by a dorsal ribbon of
      chromaffin cells, generally defined as medullary tissue, arranged along a central
      part of steroidogenic cells considered as cortical tissue. These two tissues
      produce catecholamines and steroids as part of the hypothalamo-hypophyseal
      adrenal gland axis. Recent studies have demonstrated that Podarcis sicula adrenal
      gland is not only under hypothalamo-hypophyseal axis control but that several
      peptides may influence the physiological activity of the gland; among these,
      vasoactive intestinal peptide is able to enhance strongly both catecholamine and
      steroid hormone production. The aim of the present study was to verify whether
      vasoactive intestinal peptide administration could become deleterious. For this
      reason, we monitored the pattern of expression of two members of the Bcl-2
      family, Bcl-2 and Bax, in control and vasoactive intestinal peptide treated
      specimens. Furthermore, we also tested if peptide treatment induces apoptosis by
      TUNEL assay.

PMID- 12197673
TI  - Age-dependent expression of 8-hydroxy-2'-deoxyguanosine in human pituitary gland.
AB  - A major oxidative product, 8-hydroxy-2'-deoxyguanosine (8-OHdG) is involved in
      ageing, carcinogenesis, and different diseases. The expression of 8-OHdG in the
      human pituitary gland was investigated immunohistochemically using specimens from
      individuals aged 19-88 years. 8-OHdG was localized at the nuclei of the anterior
      lobar parenchymal cells of the pituitary gland. The number of cells positive for
      8-OHdG were counted, and the ratio of the positive cells to the total parenchymal
      cells was evaluated. The ratios increased in accordance with the ages of the
      individuals examined. Statistically, there was a significant correlation between
      the ages in years and the 8-OHdG positive ratios in the anterior lobar
      parenchymal cells (r = 0.757, p < 0.01). These findings indicate an age-dependent
      accumulation of 8-OHdG in the pituitary gland, which may also be related to the
      ageing of neuroendocrine systems as well.

PMID- 12197674
TI  - Distribution of acid phosphatases in the hypopharyngeal glands from workers,
      queens and males of a Brazilian stingless bee Scaptotrigona postica Latreille: an
      ultrastructural cytochemical study.
AB  - The present study reports the localization of acid phosphatase in the
      hypopharyngeal gland cells from workers (newly-emerged, nurse and forager),
      queens (newly-emerged and laying) and males (newly-emerged and mature for mating)
      of the Brazilian stingless bee, Scaptotrigona postica. The phosphatase activity
      varied in intensity and localization depending on the individual class,
      physiological age and the substrate used. In newly-emerged workers, the
      phosphatase-positive sites suggest the involvement of the enzyme with cellular
      differentiation that occurs in the presecretory phase, in nurse workers with
      protein synthesis and in forager workers with changes in cellular activity or
      glandular regression. In males mature for mating and laying queens, the positive
      sites are related to secretory activity, showing that the gland maintains some
      activity in spite of the regressive aspect. Of the substrates used, beta
      glycerophosphate gave the least specific localization.

PMID- 12197675
TI  - Histopathological alterations and induction of cytochrome P-450 1A in the liver
      and gills of the gilthead seabream (Sparus aurata) exposed to 2,3,7,8
      tetrachlorodibenzo-p-dioxin.
AB  - The toxicity of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) has been demonstrated
      in the seabream Sparus aurata specimens. Liver presented hepatocytic alterations,
      with an increase of lipid droplets and glycogen granules. Ultrastructural
      modifications of hepatocytes included RER fractionation, glycogen augmentation,
      as well as a rise in the number of lipid droplets, vacuoles and secondary
      lysosomes. In the gills, secondary lamellar epithelium showed hyperplasia,
      hypertrophy and lamellar fusion on the edge of the filaments. At the end of the
      exposure period (1 pg1(-1) TCDD for 20 days), some organelles in epithelial cells
      of the secondary lamellae and the tubular system of the chloride cells appeared
      altered. In the liver of TCDD-exposed specimens, immunoreactive cytochrome P-450
      1A was concentrated close to the cytoplasmic and nuclear membranes, and positive
      granules were also evident throughout cytoplasm of the hepatocytes. Significant
      cytochrome P-450 staining was especially evident in endothelium of the hepatic
      vascular system. At the beginning of the exposure (1 pg 1(-1) TCDD, for 5 and 10
      days), cytochrome P-450 immunostaining was observed in the cytoplasm of scarce
      hepatic cells and after 20 days of treatment, specific immunostained cytoplasmic
      granules were detected in most hepatocytes. In gills of TCDD-treated specimens,
      pillar-endothelial cells showed a cytochrome P-450 1A immunostaining concentrated
      close to the base of gill filaments and dispersed through the gill lamellae.
      There was also significant cytochrome staining of the endothelium of the
      branchial vascular system. However, no cytochrome immunoreactivity was observed
      in epithelial-respiratory cells.

PMID- 12197676
TI  - Behaviour of a somatotroph population under a growth hormone releasing peptide
      treatment.
AB  - In this investigation, we studied the effects of Momany peptide (GHRP-5), on
      somatotroph secretory activity. Acute and chronic administration of GHRP-5
      provokes a significant release of growth hormone that can be closely correlated
      with ultrastructural changes in somatotroph populations. After 3,5 and 7 days of
      GHRP-5 treatment, two somatotroph cell subpopulations coexist. One of them has an
      enhanced secretory activity and the other presents a quiescent appearance.
      Therefore, pituitary growth hormone content was not affected in the first seven
      days of GHRP-5 treatment. After 14 days, there was a significant depletion of
      growth hormone pituitary content coincident with the highest levels of serum
      growth hormone. These results concur with the surge of a new hyperactive
      somatotroph subtype characterised by numerous immature secretory granules that
      are discharged bypassing the maturation step. Acute and chronic treatments caused
      no changes in somatotroph cell density, the area immunostained for growth hormone
      and the levels of total mRNA for transcription factor pit-1. The results of
      pituitary cell cultures incubated with specific blockers for different signalling
      pathways demonstrated an involvement of the phospholipase C-inositol phosphate
      system in GHRP-5 stimulated somatotroph secretion. GHRP-5 treatment enhanced
      significantly the release of growth hormone, thereby eliciting ultrastructural
      modifications in somatotrophs that can be correlated with an increased secretory
      activity devoid of cell density changes.

PMID- 12197677
TI  - Corticotropin-releasing hormone-like immunoreactivity in the brain of the snake
      Bothrops jararaca.
AB  - The distribution of corticotropin-releasing hormone in the brain of the snake
      Bothrops jararaca was studied immunohistochemically. Immunoreactive neurons were
      detected in telencephalic, diencephalic and mesencephalic areas such as dorsal
      cortex, subfornical organ, paraventricular nucleus, recessus infundibular
      nucleus, nucleus of the oculomotor nerve and nucleus of the trigeminal nerve.
      Immunoreactive fibres ran along the hypothalamo-hypophysial tract to end in the
      outer layer of the median eminence and the neural lobe of the hypophysis. In
      general, immunoreactive fibres occurred in the same places of immunoreactive
      neurons. In addition, immunoreactive fibres were observed in the septum,
      amygdala, lamina terminalis, supraoptic nucleus, nucleus of the paraventricular
      organ, ventromedial hypothalamic nucleus and interpeduncular nucleus. These
      results indicate that, as for other vertebrates, corticotropin-releasing hormone
      in B. jararaca brain, besides being a releasing hormone, may also act as a
      central neurotransmitter and/or neuromodulator.

PMID- 12197678
TI  - Effects of multiple somatostatin treatment on rat gonadotrophic cells and
      ovaries.
AB  - The effect of multiple somatostatin (SRIH-14) treatment on the pituitary
      gonadotrophs, follicle stimulating harmone (FSH) and luteinizing harmone (LH),
      and ovaries of adult female Wistar rats was examined. Females received two 20
      microg/100 g body wt. doses daily subcutaneously, for five consecutive days. FSH
      and LH cells were studied using a peroxidase-antiperoxidase immunocytochemical
      procedure. Morphometry and stereology were used to evaluate changes in the number
      per unit area (mm2), cell volume and volume densities of LH- and FSH
      immunoreactive cells. Ovaries were analysed by simple point counting of follicles
      and corpora lutea. Follicles were divided by size according to the classification
      of Gaytan and Osman. Morphometric and stereological analysis of the pituitary
      showed that the number, volume and the volume density of FSH- and LH
      immunoreactive cells were decreased after multiple SRIH-14 treatment,
      particularly in the latter. In the ovary, SRIH-14 induced decreases in the number
      of healthy follicles in all phases of folliculogenesis and corpora lutea, but the
      large antral follicle stage was most affected. The number of atretic follicles
      was increased. It can be concluded that multiple SRIH-14 treatment markedly
      inhibited LH cells, but affected FSH cells as well. In the ovary, SRIH- 14 acted
      by inhibiting folliculogenesis and enhancing atretic processes.

PMID- 12197679
TI  - One conclusion may hide another.

PMID- 12197680
TI  - Butting heads over bicycle helmets.

PMID- 12197681
TI  - Butting heads over bicycle helmets.

PMID- 12197682
TI  - Butting heads over bicycle helmets.

PMID- 12197683
TI  - Interpreting the Quebec prostate cancer study.

PMID- 12197684
TI  - PSA screening: correlating noise with noise?

PMID- 12197685
TI  - Where there's a will, there's a way: a letter from the President of the CMA.

PMID- 12197686
TI  - Predictors of survival following in-hospital adult cardiopulmonary resuscitation.
AB  - BACKGROUND: This study was undertaken to provide up-to-date survival data for
      Canadian adult in-patients following attempted resuscitation from cardiac or
      respiratory arrest. We hope that objective data might encourage more meaningful
      dialogue between physicians, patients and their families regarding resuscitation
      wishes. METHODS: We reviewed all records of adult cardiopulmonary arrest that
      occurred between Jan. 1, 1997, and Jan. 31, 1999, at the 3 main teaching
      hospitals in Edmonton. We then abstracted data from the full inpatient medical
      records to describe patient characteristics, type of arrest and survival details.
      The family physicians of survivors were contacted to confirm the outcomes. We
      included only adults admitted to hospital but not to a critical care bed.
      RESULTS: There were 247 arrests during the study period; 143 (57.9%) were
      witnessed, and 104 (42.1%) were unwitnessed). Of the patients whose arrests were
      witnessed, 48.3% (95% confidence interval [CI] 39.8%-56.8%) were able to be
      resuscitated, 22.4% (95% CI 1 5.8%-30.1%) survived to hospital discharge, and
      18.9% (95% CI 12.8%-26.3%) were able to return home. Survival was highest after
      primary respiratory arrest and lowest after pulseless electrical activity or
      asystole. Of the patients with unwitnessed arrests, 21.2% (95% CI 13.8%-30.3%)
      were able to be resuscitated, but only 1 patient (1.0% [95% CI 0.0%-5.2%])
      survived to hospital discharge and was able to return home. This patient survived
      an unwitnessed respiratory arrest. No patient who had an unwitnessed cardiac
      arrest survived to discharge. Most of the respiratory arrests were witnessed
      (93.1%), and most of the pulseless electrical activity or asystole arrests were
      unwitnessed (54.6%). We did not find age or sex to be independent predictors of
      survival. However, the risk of not returning home was higher among patients whose
      arrest occurred between 2301 and 0700 than among those whose arrest was between
      0701 and 1500 (adjusted OR 3.2, 95% CI 1.0-10.1). Survival was significantly
      decreased after pulseless ventricular tachycardia or ventricular fibrillation
      arrest (adjusted OR 4.2, 95% CI 1.4-12.5) and even more so after pulseless
      electrical activity or asystole arrest (adjusted OR 21.0, 95% CI 6.2-71.7) than
      after respiratory arrest. INTERPRETATION: Overall, survival following
      cardiopulmonary resuscitation in hospital does not appear to have changed
      markedly in 40 years. The type of arrest is highly predictive of survival,
      whereas age and sex are not.

PMID- 12197687
TI  - Predictors of clustering of tuberculosis in Greater Vancouver: a molecular
      epidemiologic study.
AB  - BACKGROUND: The understanding of how tuberculosis is transmitted can be improved
      by combining DNA fingerprinting of Mycobacterium tuberculosis with conventional
      epidemiologic methods. We used such techniques to determine the predictors of
      clustering of identical isolates from tuberculosis patients in Vancouver.
      METHODS: We used the restriction fragment length polymorphism (RFLP) technique
      and, if necessary, spoligotyping to determine DNA patterns of M. tuberculosis
      isolates from all patients with newly diagnosed tuberculosis in Greater Vancouver
      reported to the Division of Tuberculosis Control from January 1995 to March 1999.
      Isolates were considered to be part of a cluster if they had an identical DNA
      pattern. We also collected demographic and epidemiologic data. Predictors
      associated with being in a cluster were analyzed in a multivariate logistic
      regression model. RESULTS: Isolates from 793 patients (430 men) were identified;
      137 (17.3%) were considered to be in clusters. After adjustment for multiple
      potential predictors, we found that the following patients were more likely to be
      part of a cluster: Canadian-born Aboriginals (v. foreign-born patients) (adjusted
      odds ratio [OR] 6.0, 95% confidence interval [CI] 3.0-11.7), Canadian-born non
      Aboriginals (v. foreign-born patients) (adjusted OR 3.6, 95% CI 2.1-6.3), and
      injection drug users (v. patients who did not inject drugs) (adjusted OR 3.9, 95%
      CI 1.9-8.1). Patients with a prior history of tuberculosis were less likely to be
      part of a cluster than were patients with no history of tuberculosis (adjusted OR
      0.3, 95% CI 0.1-0.8). INTERPRETATION: Our findings indicate the need to target
      groups at high risk of tuberculosis more aggressively to prevent transmission and
      to treat latent infection. DNA fingerprinting may be a useful adjunct to
      conventional epidemiologic methods to monitor the transmission of tuberculosis in
      an inner-city setting.

PMID- 12197688
TI  - Molecular epidemiology of tuberculosis in Montreal.

PMID- 12197689
TI  - Molecular epidemiology and the dynamics of tuberculosis transmission among
      foreign-born people.

PMID- 12197690
TI  - Hormone replacement therapy: a time for pause.

PMID- 12197691
TI  - Lessons from the Women's Health Initiative: primary prevention and gender health.

PMID- 12197692
TI  - The arrogance of preventive medicine.

PMID- 12197693
TI  - Retaining Canada's health care system as a global public good.

PMID- 12197694
TI  - Medical genetics: 2. The diagnostic approach to the child with dysmorphic signs.
AB  - Dysmorphology is the branch of clinical genetics in which clinicians and
      researchers study and attempt to interpret the patterns of human growth and
      structural defects. Reaching an accurate diagnosis for children with dysmorphic
      signs is important to their families, because it makes available all the
      accumulated knowledge about the relevant condition and may provide the family
      with the opportunity for interaction with patient or parent support groups. I
      show in this review that reaching a diagnosis in dysmorphology involves an
      approach that is not fundamentally different from that of other medical
      disciplines. Cytogenetic and molecular techniques continue to improve our ability
      to make precise syndrome diagnoses; however, these tests are expensive and should
      be used selectively.

PMID- 12197695
TI  - Genetics 101: cytogenetics and FISH.

PMID- 12197696
TI  - Antimicrobial resistance takes another step forward.

PMID- 12197697
TI  - Postmenopausal hormone replacement therapy for chronic disease prevention:
      results from the Women's Health Initiative trial.

PMID- 12197698
TI  - Tamoxifen for breast cancer prevention: safety warning.

PMID- 12197699
TI  - A woman with a mummified leg.

PMID- 12197705
TI  - Principles concerning physician information.

PMID- 12197703
TI  - Poverty leading cause of cardiovascular disease in Canada.

PMID- 12197706
TI  - Single-bubble sonochemiluminescence in aqueous luminol solutions.
AB  - Sonochemiluminescence (SCL) of luminol due to a single bubble is studied through
      spectral measurement. No SCL was observed from a stable single bubble that
      emitted high-intensity sonoluminescence (SL). In contrast, SCL was observed under
      conditions of an unstable dancing bubble, where a bubble grows and ejects tiny
      bubbles, making it "dance" by counteraction. Furthermore, SCL was observed from
      dancing bubbles even when SL was not observed, depending on the dissolved gas
      content. The instability of bubble collapse is the key parameter governing SCL.

PMID- 12197707
TI  - Photoinduced electron transfer in hydrogen-bonded oligo(p-phenylene vinylene)
      perylene bisimide chiral assemblies.
AB  - Well-defined chiral fibers incorporating hydrogen-bonded oligo(p-phenylene
      vinylene) donor and perylene bisimide acceptor chromophores have been realized by
      self-assembly. Upon photoillumination of these fibers electron-transfer takes
      place, leading to charge separation within the aggregated dyes.

PMID- 12197708
TI  - Fluorescent probes for cytochrome p450 structural characterization and inhibitor
      screening.
AB  - We have synthesized two luminescent probes (D-4-Ad and D-8-Ad) that target
      cytochrome P450cam. D-4-Ad luminescence is quenched by Forster energy transfer
      upon binding (Kd = 0.83 muM) but is restored when the probe is displaced from the
      active site by camphor. In contrast, D-8-Ad (Kd approximately 0.02 muM) is not
      displaced from the enzyme, even in the presence of a large excess of camphor. The
      2.2 A resolution crystal structure of the D-8-Ad:P450cam complex reveals
      extensive hydrophobic contacts between the probe and the enzyme, which result
      from the conformational flexibility of the B', F, and G helices. Probes with
      properties similar to those of D-4-Ad potentially could be useful for screening
      P450 inhibitors.

PMID- 12197709
TI  - A general mass spectrometry-based assay for the quantitation of protein-ligand
      binding interactions in solution.
AB  - A new method that utilizes matrix-assisted laser desorption/ionization (MALDI)
      mass spectrometry and exploits the hydrogen/deuterium (H/D) exchange properties
      of proteins was developed for measuring the thermodynamic properties of protein
      ligand complexes in solution. Dissociation constants (Kd values) determined by
      the method for five model protein-ligand complexes that included those with small
      molecules, nucleic acids, peptides, and other proteins were generally in good
      agreement with Kd values measured by conventional methods. Important experimental
      advantages of the described method over existing methods include: the ability to
      make measurements in a high-throughput and automated fashion, the ability to make
      measurements using only picomole quantitities of protein, and the ability to
      analyze either purified or unpurified protein-ligand complexes.

PMID- 12197710
TI  - Tris(eta4-naphthalene)- and tris(1-4-eta4-anthracene)tantalate(1-): first
      homoleptic arene complexes of anionic tantalum.
AB  - Reduction of tantalum pentachloride by 6 equiv of sodium naphthalene in 1,2
      dimethoxyethane provided, after recrystallization from tetrahydrofuran, 50-55%
      yields of yellow, pyrophoric [Na(THF)][Ta(C10H8)3]. The product was shown by 1H
      and 13C NMR spectra and an X-ray study (on the corresponding [Na(crypt
      2.2.2)]salt) to be tris(eta4-naphthalene)tantalate(1-), 1, the first homoleptic
      naphthalene complex of a third row (5d) transition metal. Salts of 1 react under
      mild conditions with excess CO (1 atm pressure, -60 degrees to +20 degrees C) and
      3 equiv of anthracene, C14H10 (20 degrees C), to give 99 and 52% yields of yellow
      [Ta(CO)6]- and orange [Ta(C14H10)3]-, (2), respectively. The latter is the first
      homoleptic anthracene complex of a group 5 element and only the third one known,
      the others being Cr(eta6-C14H10)2 and [Co(eta4-C14H10)2]-. NMR spectra and X-ray
      structural characterization, as the [Na(crypt 2.2.2)] salt, established 2 to be
      [Ta(1-4-eta4-C14H10)3]- and is very similar to 1 in solution and in the solid
      state. Salts of 2 also undergo facile ligand substitution reactions. For example,
      it reacts with 1,3,5,7-cyclooctatetraene, COT, at 20 degrees in THF to give high
      yields of the previously known [Ta(COT)3]-, which was structurally characterized
      as the Na(crypt 2.2.2)salt. One particularly important feature concerning 1 and 2
      is that they are the first available synthons for "naked" atomic Ta- and promise
      to be useful reagents for the general exploration of low-valent tantalum
      chemistry. Also, 1 and 2 represent the first homoleptic arene tantalum complexes
      to have been prepared by conventional syntheses. The only previously known
      substance of this class is the neutral bis(benzene)tantalum(0), which was
      accessed by the co-condensation of atomic tantalum and benzene vapor in a
      sophisticated (electron-gun furnace equipped) metal atom reactor.

PMID- 12197711
TI  - Structures of the muraymycins, novel peptidoglycan biosynthesis inhibitors.
AB  - The muraymycins, a family of nucleoside-lipopeptide antibiotics, were purified
      from the extract of Streptomyces sp. LL-AA896. The antibiotics were purified by
      chromatographic methods and characterized by NMR spectroscopy, degradation
      studies, and mass spectrometry. The structures of 19 compounds were established.
      The muraymycins constitute a new antibiotic family whose core structure contains
      a glycosylated uronic acid derivative joined by an aminopropane group to a
      hexahydro-2-imino-4-pyrimidylglycyl residue (epicapreomycidine) containing
      dipeptide that is further extended by a urea-valine moiety. Members of this
      family show broad-spectrum in vitro antimicrobial activity against a variety of
      clinical isolates (MIC 2 to >64 mug/mL). The muraymycins inhibited peptidoglycan
      biosynthesis. The fatty acid substituent and the presence or absence of the amino
      sugar play important roles in biological activity. One of the most active
      compounds, muraymycin A1, demonstrated protection in vivo against Staphylococcus
      aureus infection in mice (ED50 1.1 mg/kg).

PMID- 12197712
TI  - Site-specific discrimination of Cytosine and 5-methylcytosine in duplex DNA by
      Peptide nucleic acids.
AB  - For site-specific discrimination of cytosine (C) and 5-methylcytosine (mC) in
      duplex DNA, we developed a new method using peptide nucleic acids (PNAs). The
      combination of a PNA-assisted DNA displacement complex and a fluorescein-labeled
      probe oligomer allowed the detection of mC at the defined sites in target DNA
      using a restriction enzyme. After treatment of the complex with a restriction
      enzyme, strong fluorescence emission was observed for the complex containing C at
      the target site, whereas the fluorescence intensity for the complex containing mC
      was extremely weak.

PMID- 12197714
TI  - Theoretical interpretation of switching in experiments with single molecules.
AB  - Identifying the factors that trigger current-switching behavior of single
      molecules establishes the means by which it may be possible to tailor these
      molecules to perform as electronic devices. We provide a theoretical
      interpretation of switching observed in recent experiments with single molecules
      using quantum chemistry tools. We conclude that the switching observed in the
      experiment is mostly due to conformational changes and that some charge changes
      cannot be observed in STM experiments.

PMID- 12197713
TI  - Hydrogen exchange rates in proteins from water (1)H transverse magnetic
      relaxation.
AB  - Access to the fast exchange kinetics of labile protein hydrogens in solution is
      provided by exchange broadening of the water 1H NMR line. We analyzed the
      chemical shift modulation contribution of labile hydrogens in bovine pancreatic
      trypsin inhibitor (BPTI) to the transverse 1H spin relaxation rate, R2, of the
      bulk solvent. Both the experimental pH dependence and the CPMG dispersion of R2
      could be quantitatively accounted for on the basis of known chemical shifts,
      exchange rates, and ionization constants for BPTI. This analysis provided, for
      the first time, the hydrogen exchange rate constants for Lys and Arg side chains
      in a protein and pointed to an internal catalysis of the N-terminal amino protons
      in BPTI by a salt bridge. The method can be used for mapping the hydrogen
      exchange rates in protein solutions and biomaterials, which may be important for
      the control of relaxation-weighted contrast in biological MRI.

PMID- 12197715
TI  - Nanocluster with one missing core atom: a three-dimensional hybrid superlattice
      built from dual-sized supertetrahedral clusters.
AB  - In addition to having size-dependent properties, nanoclusters also behave like
      large pseudo-atoms and serve as building blocks for the construction of
      superlattices with properties that differ from either individual clusters or the
      bulk. While colloidal nanoparticles usually self-assemble into close-packed
      lattices, supertetrahedral clusters that are regular fragments of the zinc blende
      type lattice can form covalent lattices with large pore size and high pore
      volume. Unfortunately, the size of the known supertetrahedral cluster is still
      small, and only a few types are currently known. In addition, their superlattices
      invariably consist of clusters of identical size. Here we report an open
      framework sulfide (denoted as UCR-15) that extends the cluster size from 20 metal
      ions in a T4 supertetrahedron to 34 metal ions in a novel T5 supertetrahedron
      with a missing core atom, [In34S54]6-. T5 clusters are joined by smaller T3
      clusters (i.e., [In10S18]6-) to form an extended superlattice. UCR-15 is the
      first example of a covalent open framework built from supertetrahedral clusters
      of different sizes, thus revealing new possibilities in the construction of
      crystalline nanoporous semiconducting superlattices. It is proposed here that the
      formation of the dual-sized T3 and T5 hybrid framework is related to the host
      guest charge density matching.

PMID- 12197716
TI  - Fluorescence maxima of 10-methylacridone-metal ion salt complexes: a convenient
      and quantitative measure of lewis acidity of metal ion salts.
AB  - Aromatic carbonyl compounds such as 10-methylacridone form the Lewis acid
      complexes including paramagnetic and redox active Lewis acids. The fluorescence
      energies of the Lewis acid complexes are well correlated with the O2*--Lewis acid
      complexes derived from the gzz-values of the ESR spectra of the superoxide anion
      Lewis acid complexes, thus providing a quantitative measure of the Lewis acidity.

PMID- 12197717
TI  - Kinetic resolution of atropisomeric amides.
AB  - We have demonstrated the feasibility of the kinetic resolution of atropisomeric
      amides using the commercially avaliable AD-mix. To our knowledge, this
      methodology represents the first catalytic kinetic resolution of such compounds.
      Relative rates of up to 32 have been found for the kinetic resolution processes.
      We have also determined the barriers to rotation and half-lives of some of these
      amides. The half-lives range from 7 to 135 h at room temperature.

PMID- 12197718
TI  - Total synthesis of the antiviral glycolipid cycloviracin B.
AB  - The first total synthesis of the antiviral agent cycloviracin B1 (1) is described
      which provisionally establishes the hitherto unknown configuration of the chiral
      centers on the lateral fatty acid chains as (3R,19S,25R,3'R,17'S,23'R). Key steps
      en route to this glycolipid include a highly efficient template-directed
      macrodilactonization step for the formation of the lactide core followed by a two
      directional synthesis strategy for the completion of the fatty acid annexes. The
      latter comprises a modified Julia-Kocienski olefination carried out in the
      presence of the base-labile beta-hydroxyester moieties of the macrodiolide, as
      well as a titanium-catalyzed asymmetric addition of the dialkylzinc reagent 11
      controlled by cyclohexane-1,2-diamine bistriflate 12 for the formation of the
      chiral center at C-17' which is selectively glycosylated by taking recourse to
      the trichloroacetimidate method.

PMID- 12197719
TI  - CO(2) as a separation switch for ionic liquid/organic mixtures.
AB  - A novel technique to separate ionic liquids from organic compounds is introduced
      which uses carbon dioxide to induce the formation of an ionic liquid-rich phase
      and an organic-rich liquid phase in mixtures of methanol and 3-butyl-1-methyl
      imidazolium hexafluorophosphate ([C4mim][PF6]). If the temperature is above the
      critical temperature of CO2 then the methanol-rich phase can become completely
      miscible with the CO2-rich phase, and this new phase is completely ionic liquid
      free. Since CO2 is nonpolar, it is not equipped to solvate ions. As the CO2
      dissolves in the methanol/[C4mim][PF6] mixture, the solvent power of the CO2
      expanded liquid is significantly reduced, inducing the formation of the second
      liquid phase that is rich in ionic liquid. This presents a new way to recover
      products from ionic liquid mixtures and purify organic phases that have been
      contaminated with ionic liquid. Moreover, these results have important
      implications for reactions done in CO2/ionic liquid biphasic mixtures.

PMID- 12197720
TI  - New method of fluorination using potassium fluoride in ionic liquid:
      significantly enhanced reactivity of fluoride and improved selectivity.
AB  - We have found the new nucleophilic fluorination reaction of some halo- and
      mesylalkanes to the corresponding fluoroalkanes with KF in the presence of
      [bmim][BF4] under various reaction conditions. 2-(3
      Methanesulfonyloxypropoxy)naphthalene (1) was used as a model compound to
      optimize this fluorination reaction. Whereas the fluorination of the mesylate 1
      with KF in an organic solvent such as CH3CN at 100 degrees C occurred hardly even
      after 24 h, the same reaction in ionic liquids, [bmim][BF4], as a reaction
      solvent was completed within 1.5 h, affording the wanted product 2-(3
      fluoropropoxy)naphthalene 2a (85%) together with the alkene byproduct 2c (10%).
      Very interestingly, however, the addition of water (5 equiv) completely
      eliminated the formation of the undesired alkene 2c and thus gave higher yield of
      2a (92%, entry 2). The use of acetonitrile as a cosolvent did not affect the
      reactivity of the fluorination. The presence of a proper amount of cosolvent was
      rather desirable (94% yield of 2a). We performed fluorination reactions with
      other ionic liquids ([bmim][PF6], [bmim][SbF6], [bmim][OTf], and [bmim][N(Tf)2],
      and two other cosolvents, to find the optimal ionic liquid and cosolvent. Nine
      different compounds were examined, including the 10 g-synthesis of 2
      (fluoromethyl)naphthalene in 93% of isolated yield.

PMID- 12197721
TI  - Facile hydrometalation of alkynes by nido-1,2-(CpRuH)(2)B(3)H(7) yielding novel
      Ru-B edge-bridging alkylidenes. Stepwise conversion of HCtbd1;CC(O)OMe into nido
      1,2-(CpRuH)(2)-3-HOB-4-MeC-5-MeOC-BH(3), Cp = eta(5)-C(5)Me(5).
AB  - The reaction of the alkyne HCCC(O)OMe with 7 sep 1,2-(Cp*RuH)2B3H7 leads to
      hydroboration plus hydroruthenation to produce nido-1,3-mu-Me{C(O)OMe}C-1,2
      (Cp*Ru)2B3H7, a compound with an exocluster ruthenium-boron mu-alkylidene that
      exists in two isomeric forms. Both isomers undergo rearrangement with
      intramolecular chelation of the carbonyl oxygen at a boron site, thereby opening
      the cluster and generating arachno-2,3,-mu(C)-5-eta1(O)-Me{C(O)OMe}C-1,2
      (Cp*Ru)2B3H7. Further heating leads to deoxygenation of the carbonyl fragment by
      a boron center concurrent with insertion of the carbon atom into the
      metallaborane cage to give nido-1,2-(Cp*RuH)2-3-HOB-4-MeC-5-MeOC-BH3.

PMID- 12197722
TI  - New approach to the stereoselective synthesis of metalated dienes via an
      isomerization-elimination sequence.
AB  - Treatment of Cp2ZrBu2 with enol ether containing a remote double bond lead to
      conjugated metalated diene as single isomer via a tandem isomerization
      elimination sequence. 2-Arylsulfonyl 1,3-dienes can also be used as a source of
      dienyl zirconocene derivatives, and the stereochemistry of the diene is dependent
      on the transmetalation reaction.

PMID- 12197723
TI  - Electrochemical synthesis and characterization of conducting polymers in
      supercritical carbon dioxide.
AB  - This contribution reports the first synthesis of conducting polymers (CPs),
      specifically, polyaniline (PAn) and polypyrrole (PPy), in supercritical carbon
      dioxide (scCO2). CPs synthesized electrochemically in scCO2 were characterized
      with cyclic voltammetry (CV), four-point probe conductivity, scanning electron
      microscopy (SEM), and UV-vis spectroscopy. Preliminary data indicate that CPs
      synthesized by this method exhibit novel morphology and high conductivity
      comparable to that synthesized by traditional methods.

PMID- 12197725
TI  - A chiral acrylate equivalent for metal-free Diels-Alder reactions: endo-2
      acryloylisoborneol.
AB  - The principle of metal-free activation of enones toward the Diels-Alder reaction
      with dienes is demonstrated by exploiting the capability of Bronsted acids to
      activate alpha'-hydroxyenones through hydrogen bonding. The diastereoselective
      application of such a principle is nicely realized by using a newly designed
      family of camphor-based chiral enones, which upon catalytic action of either
      trifluoroacetic or triflic acid lead to the corresponding cycloadducts with high
      chemical and stereochemical efficiency.

PMID- 12197724
TI  - Concomitant C-ring Expansion and D-ring formation in lanosterol biosynthesis from
      squalene without violation of Markovnikov's rule.
AB  - A mechanism is proposed for the formation of the C and D rings of lanosterol from
      squalene on the basis of density functional calculations of a model
      cyclopentylcarbinyl carbocation. The mechanism involves the ring expansion of the
      cyclopentylcarbinyl carbocation to the six-membered ring C in concert with the
      formation of the D ring. The mechanism does not involve a violation of
      Markovnikov's rule as the earlier proposed mechanism does for the formation of
      rings C and D.

PMID- 12197726
TI  - Magneto-stimulated hydrodynamic control of electrocatalytic and
      bioelectrocatalytic processes.
AB  - Magnetic rotation of redox-functionalized magnetite particles leads to enhanced
      electrocatalysis and bioelectrocatalysis.

PMID- 12197727
TI  - Traveling fronts of copper deposition.
AB  - We report the experimental observation of traveling fronts during the electroless
      deposition of copper on passive steel substrates. The low-carbon steel samples
      are passivated in nitric acid prior to the plating experiment, thus creating a
      thin, protective oxide layer on the steel surface. The deposition experiments are
      carried out from slightly acidic (pH 3.2) copper sulfate solution and copper
      nitrate solution with the latter showing front propagation only in the presence
      of chloride ions. For up to 30 s, fronts propagate with constant velocities in
      the range from 0.5 to 5 mm/s depending on the experimental conditions. This phase
      of constant-speed propagation gives way to accelerating fronts and very rapid,
      spatially unstructured deposition. Front-mediated plating is observed over a wide
      range of cupric ion concentration and constitutes a striking and unexpected
      example for pattern formation in electrochemical systems.

PMID- 12197728
TI  - Skeletal reorganization of enynes to 1-vinylcycloalkenes catalyzed by GaCl(3).
AB  - The skeletal reorganization of enynes is achieved by the presence of GaCl3 as the
      catalyst. This reaction demonstrates the first example of the skeletal
      reorganization of enynes catalyzed by typical metal complexes. The process is
      simple and provides a diverse range of enynes in good to high yields. The
      reaction of enynes bearing a monosubstituent at the terminal olefinic carbon
      proceeds in a stereospecific manner with respect to the geometry of the olefin
      moiety. Enynes, bearing two substituents at the olefinic terminal carbon, undergo
      an efficient skeletal reorganization, these substrates having been known to be
      unsuitable substrates for the skeletal reorganization of enynes.

PMID- 12197729
TI  - Enantioselective synthesis of cyclopentenones via rhodium-catalyzed kinetic
      resolution and desymmetrization of 4-alkynals.
AB  - We have developed two new catalytic processes that provide efficient access to
      interesting chiral building blocks, cyclopentenones that bear tertiary and
      quaternary stereocenters, in high enantiomeric excess and very good yield.
      Structures such as these have potential utility in the synthesis of
      prostaglandins, pentenomycins, and related compounds.

PMID- 12197730
TI  - A highly enantioselective catalytic intramolecular Stetter reaction.
AB  - A family of chiral triazolium salts has been developed for inducing the
      asymmetric intramolecular Stetter reaction. The use of an aminoindanol-derived
      catalyst affords optimal results, with the product keto esters formed in 82-97%
      ee and very good chemical yield. Aromatic and aliphatic aldehydes are equally
      competent substrates for this reaction. The reaction conditions are reasonably
      mild and allow the isolation of the newly formed stereocenter without
      epimerization, although the presumed carbenic intermediates are strong bases.

PMID- 12197731
TI  - A new method for the preparation of silyl enol ethers from carbonyl compounds and
      (trimethylsilyl)diazomethane in a regiospecific and highly stereoselective
      manner.
AB  - The reaction of lithium (trimethylsilyl)diazomethane with aldehydes and ketones
      has been investigated, and it has been found that quenching at low temperature
      with MeOH followed by addition of Rh2(OAc)4 gave silyl enol ethers in high
      yields. Quenching with other electrophiles (e.g., deuterium, MeI) gave terminal
      and substituted silyl enol ethers with complete control over regio- and
      stereochemistry. The mechanism of this novel process has been mapped out through
      a combination of deuterium labeling, ReactIR, and isolation of reaction
      intermediates.

PMID- 12197732
TI  - Converting radical oligomers to a single product.
AB  - Atom-transfer radical oligomerizations of omega-alkenyl iodoacetates followed by
      rearrangemental deoligomerization via treatment with concentrated H2SO4 or
      heating led to the formations of gamma-lactones in high yield, demonstrating the
      important value of radical oligomers in organic synthesis.

PMID- 12197733
TI  - Multistep small-molecule synthesis programmed by DNA templates.
AB  - The translation of DNA sequences into synthetic products is a key requirement of
      our approach to evolving synthetic molecules through iterated cycles of
      translation, selection, and amplification. Here we report general linker and
      purification strategies for sequence-specific DNA-templated synthesis that
      collectively enable the product of a DNA-templated reaction to be isolated and to
      undergo subsequent DNA-templated reactions. Using these strategies, we have
      achieved the first multistep nucleic acid-templated small-molecule syntheses to
      generate two different molecules. In addition to representing a method for
      translating DNA templates sequence-specifically into corresponding multistep
      synthetic products, our findings also provide experimental support for previously
      proposed models invoking multistep nucleic acid-templated synthesis as mediating
      the prebiotic translation of replicable information into the earliest functional
      molecules.

PMID- 12197734
TI  - The electrophilic reactions of pentacyanonitrosylferrate(II) with hydrazine and
      substituted derivatives. Catalytic reduction of nitrite and theoretical
      prediction of eta(1)-, eta(2)-N(2)O bound intermediates.
AB  - The electrophilic reactivity of the pentacyanonitrosylferrate(II) ion,
      [Fe(CN)(5)NO](2)(-), toward hydrazine (Hz) and substituted hydrazines (MeHz, 1,1
      Me(2)Hz, and 1,2-Me(2)Hz) has been studied by means of stoichiometric and kinetic
      experiments (pH 6-10). The reaction of Hz led to N(2)O and NH(3), with similar
      paths for MeHz and 1,1-Me(2)Hz, which form the corresponding amines. A parallel
      path has been found for MeHz, leading to N(2)O, N(2), and MeOH. The reaction of
      1,2-Me(2)Hz follows a different route, characterized by azomethane formation
      (MeNNMe), full reduction of nitrosyl to NH(3), and intermediate detection of
      [Fe(CN)(5)NO](3)(-). In the above reactions, [Fe(CN)(5)H(2)O](3)(-) was always a
      product, allowing the system to proceed catalytically for nitrite reduction, an
      issue relevant in relation to the behavior of the nitrite and nitric oxide
      reductase enzymes. The mechanism comprises initial reversible adduct formation
      through the binding of the nucleophile to the N-atom of nitrosyl. The adducts
      decompose through OH(-) attack giving the final products, without intermediate
      detection. Rate constants for the adduct-formation steps (k = 0.43 M(-)(1) s(
      )(1), 25 degrees C for Hz) decrease with methylation by about an order of
      magnitude. Among the different systems studied, one-, two-, and multielectron
      reductions of bound NO(+) are analyzed comparatively, with consideration of the
      role of NO, HNO (nitroxyl), and hydroxylamine as bound intermediates. A DFT study
      (B3LYP) of the reaction profile allows one to characterize intermediates in the
      potential hypersurface. These are the initial adducts, as well as their
      decomposition products, the eta(1)- and eta(2)-linkage isomers of N(2)O.

PMID- 12197735
TI  - Absolute configurational assignments of secondary amines by CD-sensitive dimeric
      zinc porphyrin host.
AB  - A general chiroptical protocol for determination of absolute configuration of
      secondary amines including acyclic and cyclic aliphatic amines, aromatic amines,
      amino acids, and amino alcohols is described. The chiral substrate is linked to
      the achiral carrier moiety (3-N-Boc-amino-propyl-N-Boc-amino)acetic acid 1
      (BocHNCH(2)CH(2)CH(2)BocNCH(2)COOH), which after deprotection, yields a bidentate
      conjugate, capable of forming a 1:1 host/guest complex with dimeric zinc
      porphyrin host 2. As in the cases of primary amines and secondary alcohols
      reported earlier, the complexation of secondary amine conjugates to porphyrin
      tweezer host 2 represents a stereodifferentiating process, where the large (L)
      group at the stereogenic center (assigned on the basis of conformational energies
      A value) protrudes from the porphyrin binding pocket. This leads to formation of
      host/guest complexes with a preferred porphyrin helicity that exhibit intense
      exciton split CD spectra. It was found that the chiral sense of porphyrin twist
      is clearly controlled by the stereogenic center despite the Z/E conformational
      complexity around the tertiary amide bond of secondary amine conjugates that has
      greatly hampered previous configurational assignments. Thus, in cases where there
      is no ambiguity regarding the relative steric size of substituents, the observed
      CD couplet can be applied for straightforward assignment of absolute
      configurations. In addition, to extend the application to more difficult cases a
      molecular mechanics calculation approach using the Merck Molecular Force Field
      (MMFFs) was developed; this provides conformational information of host/guest
      complexes and leads to prediction of preferred porphyrin helicity independent of
      conformational A values. This chiroptical protocol in combination with molecular
      modeling represents a general method for configurational assignments of secondary
      amines.

PMID- 12197736
TI  - Insight into the mechanism of the asymmetric addition of alkyl groups to
      aldehydes catalyzed by titanium-BINOLate species.
AB  - The asymmetric addition of alkyl groups to aldehydes catalyzed by BINOLate
      titanium complexes has become the testing grounds to evaluate the potential of
      new BINOL-based ligands. We have investigated the mechanism of this reaction and
      report our findings here. Model systems for the open form of the catalyst,
      (BINOLate)[Ti(O-i-Pr)(3)](2), based on mono-oxygen-alkylated BINOL ligands have
      been examined. Comparison of the reactivity and enantioselectivity of the mono
      alkyl BINOL derivatives with those of BINOL indicate that the open form of the
      catalyst, (BINOLate)[Ti(O-i-Pr)(3)](2), is not active in the asymmetric addition
      reaction. Several BINOLate-titanium complexes have been synthesized and
      characterized by X-ray crystallography. These include the dinuclear
      (BINOLate)Ti(O-i-Pr)(2).Ti(O-i-Pr)(4), which contains a bridging naphtholate and
      isopropoxy group, trinuclear (BINOLate)Ti(O-i-Pr)(2).[Ti(O-i-Pr)(4)](2), and
      trimeric [(BINOL)Ti(O-i-Pr)(2)](3). The solid-state and solution structures
      reported here indicate that (BINOLate)Ti(O-i-Pr)(2) prefers to bind to titanium
      tetraisopropoxide rather than to itself, explaining why no nonlinear effects are
      observed in the catalytic reaction. Additionally, experimental evidence suggests
      that the BINOLate-titanium species responsible for the catalytic and
      stoichiometric asymmetric addition reactions are different, indicating that the
      proposed intermediate, (BINOLate)Ti(R)(aldehyde)(O-i-Pr), is not involved in
      either of these processes. Reactions were examined using different sources of the
      alkyl group [ZnMe(2) or MeTi(O-i-Pr)(3)]. Under similar conditions, it was found
      that the product ee's were the same, independent of whether ZnMe(2) or Me-Ti(O-i
      Pr)(3) was used as the source of the alkyl groups. This indicates that the role
      of the dialkylzinc is not to add the alkyl group to the carbonyl but rather to
      transfer the alkyl group to titanium. On the basis of these results, we
      hypothesize that the intermediate in the asymmetric addition involves
      (BINOLate)Ti(O-i-Pr)(2)(aldehyde).MeTi(O-i-Pr)(3).

PMID- 12197737
TI  - Metal-switching and self-inclusion of functional cavitands.
AB  - Cavitands bearing both eight (5) and two (13) metal-ligating
      carboxymethylphosphonate groups on their rims were synthesized by Arbuzov
      reaction of the corresponding bromoacetamido cavitands with trialkyl phosphites.
      These exist in the vase conformation in CDCl(3) and are stabilized by a cyclic
      seam of hydrogen bonds. This structure was also found in the solid state for the
      octabromoacetamide 4a and diphosphonate cavitand 13 by single-crystal X-ray
      analysis. Cavitands 5 and 13 form caviplexes in CDCl(3), CD(2)Cl(2), and alcohol
      solutions with adamantane derivatives 15a,b, quinuclidine 15d, ammonium and
      phosphonium salts 14, and drugs like ibuprofen 15c, all of which are stable on
      the NMR time scale at 295 K. NMR spectroscopy reveals that at 223 K
      octaphosphonate 5b exists in two forms: the major C(4)-symmetrical compound is
      filled with solvent while the minor species shows intramolecular inclusion of a
      dialkoxyphosphoryl group. In methanol-d(4) 5 and 13 exist in a lower symmetry
      vase conformation with self-inclusion of one alkyl group. Interaction of these
      complexes with La(OTf)(3) results in a change in the conformation of the cavitand
      from vase to kite with concomitant and quantitative release of the encapsulated
      guests. Two to three equivalents of the lanthanide salt per equivalent of
      cavitand 5a-d is necessary for the complete decomplexation of the included guest.
      The kite and the vase conformers equilibrate slowly on the NMR time scale at 295
      K. The addition of good ligands for metal cations (nitrate or CMPO calixarene 16)
      shifts the equilibrium to the vase-shaped caviplex and allows quantitative
      control of the binding and release of the guest. The lanthanide complexes of
      octaphosphonates 5 in methanol-d(4) are velcraplex-like dimers held together by
      four metal cations.

PMID- 12197738
TI  - The triplet-state lifetime of indole in aqueous and viscous environments:
      significance to the interpretation of room temperature phosphorescence in
      proteins.
AB  - The interpretation of room temperature phosphorescence studies of proteins
      requires an understanding of the mechanisms governing the tryptophan triplet
      state lifetimes of residues fully exposed to solvent and those deeply buried in
      the hydrophobic core of proteins. Since solvents exposed tryptophans are expected
      to behave similarly to indole free in solution, it is important to have an
      accurate measure of the triplet state lifetime of indole in aqueous solution.
      Using photon counting techniques and low optical fluence (J/cm(2)), we observed
      the triplet-state lifetime of aqueous, deoxygenated indole and several indole
      derivatives to be approximately 40 micros, closely matching the previous reports
      by Bent and Hayon based on flash photolysis (12 micros; Bent, D. V.; Hayon, E. J.
      Am. Chem. Soc. 1975, 97, 2612-2619) but much shorter than the 1.2 ms lifetime
      observed more recently (Strambini, G. B.; Gonnelli, M. J. Am. Chem. Soc. 1995,
      117, 7646-7651). However, we have now been able to reproduce the long lifetime
      reported by the latter workers for aqueous indole solutions and show that it
      likely arises from geminate recombination of the indole radical cation and
      solvated electron, a conclusion based on studies of the indole radical cation in
      water (Bent and Hayon, 1975). The evidence for this comes from a fast rise in the
      phosphorescence emission and measurements of a corresponding enhanced quantum
      yield in unbuffered solutions. This species can be readily quenched, and the
      corresponding fast rise disappears, leaving a monoexponential 40 micros decay,
      which we argue is the true indole triplet lifetime. The work is put in the
      context of room temperature phosphorescence studies of proteins.

PMID- 12197740
TI  - Modulation of tautomeric equilibria by ionic clusters. Acetylacetone in solutions
      of lithium perchlorate-diethyl ether.
AB  - Acetylacetone (2,4-pentanedione, 1) is a molecule whose tautomeric forms are in
      dynamic equilibrium. Concentrated salt solutions in nonaqueous solvents exert a
      remarkable influence on the keto-enol ratio of this beta-diketone. The keto
      content of 1 increases from 5% in pure diethyl ether to 84.5% in a 4.14 M lithium
      perchlorate-diethyl ether (LPDE) solution, a nearly 17-fold increase. The
      equilibrium expression, K = [keto]/[enol] = k(f)/k(r), exhibits a linear
      dependence on [LiClO(4)], with the formal order of participation of lithium ion
      in the equilibrium being 1.0. A kinetic analysis reveals that k(f) is independent
      of LPDE concentration, whereas k(r) displays an inverse dependence on salt
      concentration, indicating preferential coordination of the keto tautomer with
      Li(+). Although 1 exits as the enol in water only to the extent of 16%, the
      addition of lithium perchlorate further reduces this figure. In an aqueous 4.02 M
      LiClO(4) solution, acetylacetone enol accounts for only 4.6% of the total amount
      of 2,4-pentanedione present. It has also been found that acetylacetone itself is
      an excellent solvent for LiClO(4) as well as for NaClO(4) with solutions
      containing up to 7.5 M LiClO(4) attainable. The enol content of 1 decreases
      dramatically from 81% to 7.4% on going from the neat liquid to a solution of 6.39
      M LiClO(4) in acetylacetone.

PMID- 12197739
TI  - Long RNA dangling end has large energetic contribution to duplex stability.
AB  - Long terminal unpaired nucleotides known as dangling ends play interesting roles
      in biological systems. Previous studies, however, only dealt with the energy
      contributions of single dangling bases. The energy contributions of long dangling
      ends on the stability of duplexes have not been systematically studied. We now
      report a quantitative increase in stability of RNA-RNA and DNA-DNA duplexes
      containing a long dangling end. We found a larger enhancement of the stability by
      the long RNA dangling end of the RNA-RNA duplex than has been observed for the
      DNA duplexes. It is also found that structural stabilizations by long dangling
      ends seem to originate from the single-stranded stacking interactions of
      nucleotides. These results indicate that RNA stability can be achieved by
      increasing the length of the dangling end. The thermodynamic parameters of the
      long dangling ends are useful for designing ribozymes and antisense
      oligonucleotides, and for the prediction of the RNA secondary structure like the
      pseudoknot.

PMID- 12197741
TI  - Nanotubes from the self-assembly of asymmetric crystalline-coil
      poly(ferrocenylsilane-siloxane) block copolymers.
AB  - Block copolymers with a high asymmetry normally give spherical starlike micelles
      in a solvent selective for the longer block. We have discovered that samples of
      poly(ferrocenyldimethylsilane-b-dimethylsiloxane) (PFS-b-PDMS) with block ratios
      of 1:12 form nanotubes in n-hexane and n-decane, which are poor solvents for PFS.
      Two block copolymer samples PFS(40)-b-PDMS(480) (M(n) = 45 300, PDI = 1.01) and
      PFS(80)-b-PDMS(960) (M(n) = 90 500, PDI = 1.01) were synthesized by sequential
      anionic polymerization. When self-assembly occurs, the PFS blocks aggregate and
      crystallize to form a shell with a cavity in the middle of the tube, while the
      PDMS blocks form the corona. The nature of these structures was elucidated by
      conventional transmission electron microscopy and dark-field scanning
      transmission electron microscopy. Time- and temperature-dependence studies
      revealed that a variety of morphologies are formed initially depending on the
      conditions of sample preparation, but most of them eventually rearrange to form
      nanotubules. The lengths of the tubes can be varied with time and with the choice
      of solvents. We have been able to grow nanotubes with lengths reaching 0.1 mm.
      The presence of the hollow core was confirmed by trapping tetrabutyllead in the
      cavity and performing energy-dispersive X-ray measurements on the resulting
      structure.

PMID- 12197742
TI  - Callipeltoside a: total synthesis, assignment of the absolute and relative
      configuration, and evaluation of synthetic analogues.
AB  - The total synthesis of the novel antitumor agent callipeltoside A, as well as
      several analogues, is accomplished and allows assignment of the stereochemistry
      not previously established. A convergent strategy is employed wherein the target
      is dissected into three units-the core macrolactone, the sugar callipeltose, and
      a cyclopropyl bearing chain. The strategy for the synthesis of the macrolactone
      derives from employment of diastereoselective aldol reactions that emanate from
      an 11 carbon piece. The stereochemistry of the latter derives from the chiral
      pool and two asymmetric reactions-a ketone reduction using CBS-oxazaborolidine
      and a Pd catalyzed asymmetric allylic alkylation (AAA). The novelty of the latter
      protocol is its control of regioselectivity as well as absolute configuration.
      The trisubstituted olefin is generated using an alkene-alkyne coupling to create
      a trisubustituted olefin with complete control of geometry. The excellent chemo-
      and regioselectivity highlights the synthetic potential of this new ruthenium
      catalyzed process. The macrolactonization employs in situ formation of an
      acylketene generated by the thermolysis of a m-dioxolenone. Two strategies
      evolved for attachment of the side chain-one based upon olefination and a second
      upon olefin metathesis. The higher efficiency of the latter makes it the method
      of choice. A novel one pot olefin metathesis-Takai olefination protocol that
      should be broadly applicable is developed. The sugar is attached by a
      glycosylation by employing the O-trichloroacetimidate. This route provided both C
      13 epimers of the macrolactone by using either enantiomeric ligand in the Pd AAA
      reaction. It also provided both trans-chlorocyclopropane diastereomers of
      callipeltoside A which allows the C-20 and C-21 configuration to be established
      as S and R, respectively. The convergent nature of the synthesis in which the
      largest piece, the macrolatone, require only 16 linear steps imparts utility to
      this strategy for the establishment of the structure-activity relationship.
      Initial biological testing demonstrates the irrelevance of the chloro substituent
      and the necessity of the sugar.

PMID- 12197743
TI  - Synthesis, structure, and biological evaluation of novel N- and O-linked
      diinositols.
AB  - Several O-and N-linked inositols and/or aminoinositols have been prepared by
      iterative opening of epoxides and aziridines derived from homochiral
      cyclohexadiene cis-diols. The three inositols and their intermediate conduritols
      (conduramines) were tested against several glycosidases (alpha- and beta
      glucosidase, alpha- and beta-galactosidase, alpha- and beta-mannosidase) in an
      assay that measured the rate of hydrolysis of p-nitrophenolglycosides rather than
      the concentration of p-nitrophenolate. Somewhat surprisingly, the best inhibition
      was seen against beta-galactosidase with several of the compounds. The inositols
      linked through oxygen or nitrogen were subjected to calcium binding studies
      performed in NMR experiments. Detailed analysis of the title compounds by NMR
      spectroscopy has been performed, and full assignments were made. One of the
      attendant benefits of the preparation of these compounds has been expressed in
      the design and synthesis of new salen catalysts whose effectiveness has been
      compared with Jacobsen's catalyst in the epoxidation of styrene.

PMID- 12197744
TI  - Asymmetric synthesis of anti-homopropargylic alcohols from aldehydes and chiral
      sulfonimidoyl substituted bis(allyl)titanium complexes through generation and
      elimination of novel chiral alkylidenecarbene (dimethylamino)sulfoxonium ylides.
AB  - A new method for the asymmetric synthesis of anti-configured homopropargylic
      alcohols 1 is described, which features the addition of chiral sulfonimidoyl
      substituted bis(allyl)titanium complexes 3 to aldehydes, the methylation of
      sulfonimidoyl substituted homoallylic alcohols 2 at the N-atom, and the
      elimination of alkenyl (dimethylamino)sulfoxonium salts 7 with LiN(H)tBu. The
      reaction of isopropyl, cyclohexyl, and methyl substituted allylic titanium
      complexes 3a-c with benzaldehyde, p-bromobenzaldehyde, p-chlorobenzaldehyde, p
      methoxybenzaldehyde, (E)-3-phenylpropenal, and phenylpropynal afforded with high
      regio- and diastereoselectivities the anti-configured sulfonimidoyl substituted
      homoallylic alcohols 2a-j, respectively. Only one allylic unit of the titanium
      complexes 3a-c was transferred in the case of unsaturated aldehydes, and the
      starting allylic sulfoximines 2a-g were recovered in approximately 50% yield. The
      methylation of the silyl protected alkenyl sulfoximines 6a-j with Me(3)OBF(4)
      gave in practically quantitative yields the (dimethylamino)sulfoxonium salts 7a
      j, respectively. Salts 7a-e, 7g, 7h, and 7j delivered upon treatment with 2 equiv
      of LiN(H)tBu the enantio- and diastereomerically pure saturated and unsaturated
      alkynes 9a-e, 9g, 9h, and 9j, respectively, in high yields. Besides the alkynes
      the sulfinamide 8 (96% ee) was isolated. Aminosulfoxonium salts 9f and 9i, which
      carry a CC triple bond, also suffered an elimination under these conditions but
      did not yield the corresponding diynes. Elimination of salts 7a-e, 7g, 7h, and 7j
      proceeds most likely through deprotonation at the alpha-position with formation
      of the novel alkylidenecarbene aminosulfoxonium ylides 19a-e, 19g, 19h, and 19j,
      respectively. The ylides 19a-e, 19g, 19h, and 19j presumably eliminate
      sulfinamide 8 with generation of the chiral nonracemic (beta
      siloxyalkylidene)carbenes 20a-e, 20g, 20h, and 20j, which suffer a 1,2-H-shift
      with formation of alkynes 9. Support for the formation of the putative
      alkylidenecarbenes 20 as intermediates comes from the elimination of the beta
      methyl substituted aminosulfoxonium salt 24, which delivered the enantio- and
      diastereomerically pure 2,3-dihydrofuran derivative 28 upon treatment with
      LiN(H)tBu in high yield. Here, the putative (beta-siloxyalkylidene)carbene 26
      suffers a 1,5-O,Si bond insertion rather than a 1,2-Me shift. Methylation of the
      alkenyl sulfoximine 6a at the alpha-position with formation of 13 was achieved
      through deprotonation of the former with formation of the alpha-lithioalkenyl
      sulfoximine 11a and its treatment MeI. Reaction of the alpha-methylated alkenyl
      aminosulfoxonium salt 14a with LiNiPr(2) at low temperatures gave the enantio-
      and diastereomerically pure anti-configured homoallenylic alcohol derivative 15,
      while reaction of the salt with LiNiPr(2) or LiN(H)tBu at higher temperatures
      afforded the enantio- and diastereomerically pure nonterminal homopropargylic
      alcohol derivative 17. Deprotonation of the alkenyl (dimethylamino)sulfoxonium
      salts 7a and 7b with nBuLi afforded the novel alkylidenecarbene aminosulfoxonium
      ylides 19a and 19b, respectively, which upon treatment with MeI yielded the
      methylated aminosulfoxonium salts 14a and 14b, respectively.

PMID- 12197745
TI  - Stereoselective formal [3 + 3] cycloaddition approach to cis-1-azadecalins and
      synthesis of (-)-4a,8a-diepi-pumiliotoxin C. evidence for the first highly
      stereoselective 6pi-electron electrocyclic ring closures of 1-azatrienes.
AB  - Evidence is described here to support that a highly stereoselective 6pi-electron
      electrocyclic ring closure of 1-azatrienes is a key step in formal [3 + 3]
      cycloaddition or annulation reactions of chiral vinylogous amides with alpha,beta
      unsaturated iminium salts. This would represent the first highly stereoselective
      6pi-electron electrocyclic ring closure of 1-azatrienes. We have also
      unambiguously demonstrated that these specific ring closures are reversible,
      leading to the major diastereomer that is also thermodynamically more stable, and
      that a rotation preference likely also plays a role. A synthetic application is
      illustrated here to stereoselectively transform the resulting dihydropyridines to
      cis-1-azadecalins with unique anti relative stereochemistry at C2 and C2a,
      leading to synthesis of epi isomers of (-)-pumiliotoxin C.

PMID- 12197746
TI  - Solution-phase preparation of a 560-compound library of individual pure mappicine
      analogues by fluorous mixture synthesis.
AB  - Solution-phase mixture synthesis has efficiency advantages and favorable reaction
      kinetics. Applications of this technique, however, have been discouraged by the
      difficulty in obtaining individual, pure final products by using conventional
      separation and identification processes. Introduced here is a new strategy for
      mixture synthesis that addresses the separation and identification problems.
      Members of a series of organic substrates are paired with a series of fluorous
      tags of different chain lengths. The tagged starting materials are then mixed and
      taken through a multistep reaction process. Fluorous chromatography is used to
      demix the tagged product mixtures on the basis of the fluorine content of the
      tags to provide the individual pure components of the mixture, which are detagged
      to release the final products. The utility of fluorous mixture synthesis is
      demonstrated by the preparation of a 560-membered library of analogues of the
      natural product mappicine. A seven-component mixture is carried through a four
      step mixture synthesis (two one-pot and two parallel steps) to incorporate two
      additional points of diversity onto the tetracyclic core. Methods for analysis
      and purification of the intermediates are established for the quality control of
      the mixture synthesis.

PMID- 12197747
TI  - Atropselective macrocyclization of diaryl ether ring systems: application to the
      synthesis of vancomycin model systems.
AB  - Vancomycin is the last line of defense available in the clinic for treating
      multidrug-resistant bacterial infections. Vancomycin contains two 16-membered
      diaryl ether macrocycles, each of which contains a stereogenic axis across the
      diaryl ether linkage. Since an effective total synthesis of vancomycin requires
      that these stereogenic axes be formed in a stereoselective manner, we have
      developed an atropselective variation of the triazene mediated diaryl ether
      forming reaction. This variation introduced an energetic penalty into the
      transition state of the undesired atropisomer. This reaction is used to
      synthesize the C-O-D diaryl ether macrocycle found in vancomycin with high
      diastereoselectivity (de > 90%), providing the naturally occurring atropisomeric
      configuration.

PMID- 12197748
TI  - Investigations by (13)C NMR spectroscopy of ethene-initiated catalytic CO
      hydrogenation.
AB  - 13C NMR spectroscopy shows that the n-alkene and n-alkane products from the
      catalytic hydrogenation of CO in the presence of (13)C(2)H(4) probes over Ru/150
      degrees C, Co/180 degrees C, Fe/220 degrees C, or Rh/190 degrees C (1 atm,
      CO:H(2) 1:1, "mild conditions") contain terminal (13)CH(3)(13)CH(2)- units. This
      is consistent with their formation by a regiospecific polymerization of C(1)
      species derived from CO and initiated by (13)C(2)H(4). Although the activities
      toward individual products differed somewhat, similar distributions and similar
      product labeling patterns were obtained over all the four catalysts. 1-Butene and
      the higher 1-n-alkenes from all the catalysts were largely
      (13)CH(3)(13)CH(2)(CH(2))(n)()CH=CH(2) (n = 0-3), propene formed over Ru or Co
      was (13)CH(3)(13)CH=CH(2), while both (13)CH(3)(13)CH=CH(2) and
      (13)CH(2)=(13)CHCH(3) were formed over Fe or Rh. Comparison of the conclusions
      from these probe experiments with those from isotope transient experiments by
      other workers indicates that the ethene initiator does not significantly modify
      the course of the CO hydrogenation. The reaction products are largely kinetically
      determined, and the primary products are mainly linear 1-n-alkenes, while the n
      alkanes and 2-n-alkenes largely arise via secondary processes. Since the
      distribution of products and the labeling in them is so similar, it is concluded
      that one basic primary mechanism applies over all the four metals. Several
      different reaction paths involving a polymerization of surface methylene,
      [CH(2(ad))], have been proposed. Although the predictions based on several of
      these mechanisms agree with many of the results, the alkenyl + [CH(2(ad))]
      mechanism, initiated by a surface vinyl [CH(2)=CH((ad))], most easily
      accommodates the experimental evidence. An alternative path involving sequential
      addition of surface methylidyne and hydride either to a growing alkylidene chain
      (alkylidene + [CH(ad) + H(ad)]) or to an alkyl chain (alkyl + [CH((ad)) + H(ad)])
      has recently been proposed by van Santen and Ciobica. The [CH(2(ad))] mechanism
      offers an easier explanation for the formation of the various alkenes, the
      distribution of products, and of the initiation, while the [CH(ad) + H(ad)]
      mechanism can explain any n-alkanes formed as primary products and not derived
      from alkenes. At higher reaction temperatures over Ru and Co, considerable
      (13)C(1) incorporation (from natural abundance in the CO and from cleavage of the
      (13)C(2)H(4) probe) was found in all the hydrocarbons. Thus, at higher
      temperatures (13)C(1(ad)) in addition to (13)C(2(ad)) species participate in both
      chain growth and initiation. In summary, adsorbed CO is transformed very easily
      into surface C(1(ad)), probably [CH(2(ad))] in equilibrium with [CH((ad))+H(ad)],
      which act as the propagating species.

PMID- 12197749
TI  - Abnormal ligand binding and reversible ring hydrogenation in the reaction of
      imidazolium salts with IrH(5)(PPh(3))(2).
AB  - We show that imidazolium salts do not always give normal or even aromatic
      carbenes on metalation, and the chemistry of these ligands can be much more
      complicated than previously thought. N,N'-disubstituted imidazolium salts of type
      [(2-py)(CH(2))(n)(C(3)H(3)N(2))R]BF(4) react with IrH(5)(PPh(3))(2) to give N,C
      chelated products (n = 0, 1; 2-py = 2-pyridyl; C(3)H(3)N(2) = imidazolium; R =
      mesityl, n-butyl, i-propyl, methyl). Depending on the circumstances, three types
      of kinetic products can be formed: in one, the imidazole metalation site is the
      normal C2 as expected; in another, the metalation occurs at the abnormal C4 site;
      and in the third, C4 metalation is accompanied by hydrogenation of the
      imidazolium ring. The bonding mode is confirmed by structural studies, and
      spectroscopic criteria can also distinguish the cases. Initial hydrogen transfer
      can take place from the metal to the carbene to give the imidazolium ring
      hydrogenation product, as shown by isotope labeling; this hydrogen transfer
      proves reversible on reflux when the abnormal aromatic carbene is obtained as
      final product. Care may therefore be needed in the future in verifying the
      structure(s) formed in cases where a catalyst is generated in situ from
      imidazolium salt and metal precursor.

PMID- 12197750
TI  - A novel aryl amide-bridged ladderlike polymethylsiloxane synthesized by an amido
      H-bonding self-assembled template.
AB  - A novel soluble aryl amide-bridged ladderlike polymethylsiloxane (A-LPMS) was
      synthesized by stepwise coupling polymerization on the basis of amido H-bonding
      self-assembling template from monomer N,N'-bis(3-methyldiethoxylsilylpropyl)
      [4,4'-oxybis(benzyl amide)]. The monomer was prepared in a high yield by the
      hydrosilylation reaction of template agent N,N'-diallyl-[4,4'-oxybis(benzyl
      amide)] with methyldiethoxysilane in the presence of dicyclopentadienylplatinum
      dichloride (Cp(2)PtCl(2)) as catalyst. A variety of techniques including (1)H
      NMR, (13)C NMR, (29)Si NMR, FTIR, XRD, DSC, and, especially, static and dynamic
      light scattering and viscosimetry were combined to confirm the presence of the
      ordered ladderlike structure of polymer A-LPMS.

PMID- 12197751
TI  - Structure and properties of the dendron-encapsulated polyoxometalate
      (C(52)H(60)NO(12))(12)[(Mn(H(2)O))(3)(SbW(9)O(33))(2)], a first generation
      dendrizyme.
AB  - Combining analytical and theoretical methods, we present a detailed study of a
      heteropolytungstate cluster encapsulated in a shell of dendritically branching
      surfactants, namely (C(52)H(60)NO(12))(12)[(Mn(H(2)O))(3)(SbW(9)O(33))(2)], 3.
      This novel surfactant-encapsulated cluster (SEC) self-assembles spontaneously
      from polyoxometalate-containing solutions treated with a stoichiometric amount of
      dendrons. Compound 3 exhibits a discrete supramolecular architecture in which a
      single polyoxometalate anion resides in a compact shell of dendrons. Our approach
      attempts to combine the catalytic activity of polyoxometalates with the steric
      properties of tailored dendritic surfactants into size-selective catalytic
      systems. The structural characterization of the SEC is based on analytical
      ultracentrifugation (AUC) and small-angle neutron scattering (SANS). The packing
      arrangement of dendrons at the cluster surface is gleaned from molecular dynamics
      (MD) simulations, which suggests a highly porous shell structure due to the
      dynamic formation of internal clefts and cavities. From analysis of the MD
      trajectory of 3, a theoretical neutron-scattering function is derived that is in
      good agreement with experimental SANS data. Force field parameters used in MD
      simulations are partially derived from a quantum mechanical geometry optimization
      of [(Zn(H(2)O))(3)(SbW(9)O(33))(2)](12)(-), 2b, at the density functional theory
      (DFT) level. DFT calculations are corroborated by X-ray structure analysis of
      Na(6)K(6)[(Zn(H(2)O))(3)(SbW(9)O(33))(2)].23H(2)O, which is isostructural with
      the catalytically active Mn derivative 2a. The combined use of theoretical and
      analytical methods aims at rapidly prototyping smart catalysts ("dendrizymes"),
      which are structurally related to naturally occurring metalloproteins.

PMID- 12197752
TI  - Spectroscopic and electronic structure studies of the mu(4)-sulfide bridged
      tetranuclear Cu(Z) cluster in N(2)O reductase: molecular insight into the
      catalytic mechanism.
AB  - Spectroscopic methods combined with density functional calculations are used to
      develop a detailed bonding description of the mu(4)-sulfide bridged tetranuclear
      Cu(Z) cluster in N(2)O reductase. The ground state of Cu(Z) has the
      1Cu(II)/3Cu(I) configuration. The single electron hole dominantly resides on one
      Cu atom (Cu(I)) and partially delocalizes onto a second Cu atom (Cu(II)) via a
      Cu(I)-S-Cu(II) sigma/sigma superexchange pathway which is manifested by a Cu(II) 
      -> Cu(I) intervalence transfer transition in absorption. The observed excited
      state spectral features of Cu(Z) are dominated by the S --> Cu(I) charge-transfer
      transitions and Cu(I) based d-d transitions. The intensity pattern of individual
      S --> Cu(I) charge-transfer transitions reflects different bonding interactions
      of the sulfur valence orbitals with the four Cu's in the Cu(Z) cluster, which are
      consistent with the individual Cu-S force constants obtained from a normal
      coordinate analysis of the Cu(Z) resonance Raman frequencies and profiles. The
      Cu(I) d orbital splitting pattern correlates with its distorted T-shaped ligand
      field geometry and accounts for the observed low g( parallel ) value of Cu(Z) in
      EPR. The dominantly localized electronic structure description of the Cu(Z) site
      results from interactions of Cu(II) with the two additional Cu's of the cluster
      (Cu(III)/Cu(IV)), where the Cu-Cu electrostatic interactions lead to hole
      localization with no metal-metal bonding. The substrate binding edge of Cu(Z) has
      a dominantly oxidized Cu(I) and a dominantly reduced Cu(IV). The electronic
      structure description of Cu(Z) provides a strategy to overcome the reaction
      barrier of N(2)O reduction at this Cu(I)/Cu(IV) edge by simultaneous two-electron
      transfer to N(2)O in a bridged binding mode. One electron can be donated directly
      from Cu(IV) and the other from Cu(II) through the Cu(II)-S-Cu(I) sigma/sigma
      superexchange pathway. A frontier orbital scheme provides molecular insight into
      the catalytic mechanism of N(2)O reduction by the Cu(Z) cluster.

PMID- 12197754
TI  - Charge-transfer transitions in triarylamine mixed-valence systems: a joint
      density functional theory and vibronic coupling study.
AB  - A theoretical model is developed to describe the intramolecular transfer in
      organic mixed-valence systems. It is applied to rationalize the intervalence
      charge-transfer transitions in triarylamine mixed-valence compounds. The
      electronic coupling parameter is evaluated at the density functional theory (DFT)
      and time-dependent density functional theory (TD-DFT) levels. The shapes of the
      charge-transfer absorption bands are analyzed in the framework of a dynamic
      vibronic model. The influence on the optical properties of diagonal and
      nondiagonal vibronic couplings is discussed. Our results are compared to recent
      experimental data.

PMID- 12197753
TI  - Regioselective silylation of sugars through palladium nanoparticle-catalyzed
      silane alcoholysis.
AB  - Palladium(0)-catalyzed silane alcoholysis was applied to sugars for the first
      time using tert-butyldimethylsilane (TBDMS-H) and Ph(3)SiH as the silanes. The
      catalyst is a colloidal solution of Pd(0) generated in situ from PdX(2) (X = Cl(
      ), OAc(-)) and TBDMS-H in N,N-dimethylacetamide. The colloid has been
      characterized by dynamic light scattering and transmission electron microscopy
      and consists of catalytically highly active nanoparticles of approximately 2 nm
      diameter. The silane alcoholysis reaction is an effective method for the
      regioselective silylation of methyl and phenyl glycosides and generates hydrogen
      gas as the only side product. For many of the sugar substrates investigated, the
      distribution of regioisomers obtained is complementary to that of the traditional
      R(3)SiCl/base (base = pyridine, imidazole) methodology and gives convenient
      access to the 3,6- rather than the 2,6-silylated pyranosides, obtained as the
      main product by the silyl chloride method. The method also allows a selective
      axial silylation of levoglucosan and 1,3,5-O-methylidene-myo-inositol. In an
      attempt to rationalize the observed regioselectivities, ab initio predictions
      (HF/3-21G) have been made on the relative energies of some of the silylated
      products. They suggest that the observed regioselectivities do not reflect a
      kinetic vs thermodynamic product distribution but are induced by the silylation
      agent employed. Models for the possible origin of the observed regioselectivity
      in both silylation methods (silane- and silyl chloride-based) are discussed.

PMID- 12197755
TI  - Molecule-based room-temperature magnets: catalytic role of V(III) in the
      synthesis of vanadium-chromium Prussian blue analogues.
AB  - A new synthetic procedure to obtain vanadium-chromium Prussian blue analogues is
      presented, using controlled amounts of V(III) in solution during the synthesis.
      The vanadium and chromium oxidation states and the chemical environment of the
      metal ions in the solids are characterized by infrared and X-ray absorption
      spectroscopies. The presence of weak amounts of V(III) during the synthesis
      provides materials which are better organized and present reproducible Curie
      temperature and magnetization at saturation in agreement with the observed V/Cr
      stoichiometry.

PMID- 12197756
TI  - 13C and (15)N chemical shift tensors in adenosine, guanosine dihydrate, 2'
      deoxythymidine, and cytidine.
AB  - The (13)C and (15)N chemical shift tensor principal values for adenosine,
      guanosine dihydrate, 2'-deoxythymidine, and cytidine are measured on natural
      abundance samples. Additionally, the (13)C and (15)N chemical shielding tensor
      principal values in these four nucleosides are calculated utilizing various
      theoretical approaches. Embedded ion method (EIM) calculations improve
      significantly the precision with which the experimental principal values are
      reproduced over calculations on the corresponding isolated molecules with proton
      optimized geometries. The (13)C and (15)N chemical shift tensor orientations are
      reliably assigned in the molecular frames of the nucleosides based upon chemical
      shielding tensor calculations employing the EIM. The differences between
      principal values obtained in EIM calculations and in calculations on isolated
      molecules with proton positions optimized inside a point charge array are used to
      estimate the contributions to chemical shielding arising from intermolecular
      interactions. Moreover, the (13)C and (15)N chemical shift tensor orientations
      and principal values correlate with the molecular structure and the
      crystallographic environment for the nucleosides and agree with data obtained
      previously for related compounds. The effects of variations in certain EIM
      parameters on the accuracy of the shielding tensor calculations are investigated.

PMID- 12197757
TI  - Site of protonation of nicotine and nornicotine in the gas phase: pyridine or
      pyrrolidine nitrogen?
AB  - The gas-phase basicities (GBs) of nornicotine, nicotine, and model pyrrolidines
      have been measured by FT-ICR. These experimental GBs are compared with those
      calculated (for the two sites of protonation in the case of nicotine and
      nornicotine) at the B3LYP/6-311+G(3df,2p)//B3LYP/6-31G(d,p) level, or those
      estimated from substituent effects on the GBs of 2-substituted pyrrolidines, 2
      substituted N-methylpyrrolidines, and 3-substituted pyridines. It is found that,
      in contrast to the Nsp(3) protonation in water, in the gas phase nornicotine is
      protonated on the pyridine nitrogen, because the effects of an intramolecular
      CH.Nsp(3) hydrogen bond and of the polarizability of the 3-(pyrrolidin-2-yl)
      substituent add up on the Nsp(2) basicity, while the polarizability effect of the
      2-(3-pyridyl) substituent on the Nsp(3) basicity is canceled by its
      field/inductive electron-withdrawing effect. The same structural effects operate
      on the Nsp(3) and Nsp(2) basicities of nicotine, but here, the polarizability
      effect of the methyl group puts the pyrrolidine nitrogen basicity very close to
      that of pyridine. Consequently, protonated nicotine is a mixture of the Nsp(3)
      and Nsp(2) protonated forms.

PMID- 12197758
TI  - Multifrequency EPR study and density functional g-tensor calculations of
      persistent organorhenium radical complexes.
AB  - The dinuclear radical anion complexes [(mu-L)[Re(CO)(3)Cl](2)](*)(-), L = 2,2'
      azobispyridine (abpy) and 2,2'-azobis(5-chloropyrimidine) (abcp), were
      investigated by EPR at 9.5, 94, 230, and 285 GHz (abpy complex) and at 9.5 and
      285 GHz (abcp complex). Whereas the X-band measurements yielded only the
      isotropic metal hyperfine coupling of the (185,187)Re isotopes, the high
      frequency EPR experiments in glassy frozen CH(2)Cl(2)/toluene solution revealed
      the g components. Both the a((185,187)Re) value and the g anisotropy, g(1) -
      g(3), are larger for the abcp complex, which contains the better pi-accepting
      bridging ligand. Confirmation for this comes also from IR and UV/vis spectroscopy
      of the new [(mu-abcp)[Re(CO)(3)Cl](2)](o/)(*)(-)(/2)(-) redox system. The g
      values are reproduced reasonably well by density functional calculations which
      confirm higher metal participation at the singly occupied MO and therefore larger
      contributions from the metal atoms to the g anisotropy in abcp systems compared
      to abpy complexes. Additional calculations for a series of systems [(mu
      abcp)[M(CO)(3)X](2)](*)(-) (M = Tc or Re and X = Cl, and X = F, Cl, or Br with M
      = Re) provided further insight into the relationship between spin density
      distribution and g anisotropy.

PMID- 12197759
TI  - Role of the catalytic triad and oxyanion hole in acetylcholinesterase catalysis:
      an ab initio QM/MM study.
AB  - The initial step of the acylation reaction catalyzed by acetylcholinesterase
      (AChE) has been studied by a combined ab initio quantum mechanical/molecular
      mechanical (QM/MM) approach. The reaction proceeds through the nucleophilic
      addition of the Ser203 O to the carbonyl C of acetylcholine, and the reaction is
      facilitated by simultaneous proton transfer from Ser203 to His447. The calculated
      potential energy barrier at the MP2(6-31+G) QM/MM level is 10.5 kcal/mol,
      consistent with the experimental reaction rate. The third residue of the
      catalytic triad, Glu334, is found to be essential in stabilizing the transition
      state through electrostatic interactions. The oxyanion hole, formed by peptidic
      NH groups from Gly121, Gly122, and Ala204, is also found to play an important
      role in catalysis. Our calculations indicate that, in the AChE-ACh Michaelis
      complex, only two hydrogen bonds are formed between the carbonyl oxygen of ACh
      and the peptidic NH groups of Gly121 and Gly122. As the reaction proceeds, the
      distance between the carbonyl oxygen of ACh and NH group of Ala204 becomes
      smaller, and the third hydrogen bond is formed both in the transition state and
      in the tetrahedral intermediate.

PMID- 12197760
TI  - Chemical force spectroscopy in heterogeneous systems: intermolecular interactions
      involving epoxy polymer, mixed monolayers, and polar solvents.
AB  - We used chemical force microscopy (CFM) to study adhesive forces between surfaces
      of epoxy resin and self-assembled monolayers (SAMs) capable of hydrogen bonding
      to different extents. The influence of the liquid medium in which the experiments
      were carried out was also examined systematically. The molecular character of the
      tip, polymer, and liquid all influenced the adhesion. Complementary macroscopic
      contact angle measurements were used to assist in the quantitative interpretation
      of the CFM data. A direct correlation between surface free energy and adhesion
      forces was observed in mixed alcohol-water solvents. An increase in surface
      energy from 2 to 50 mJ/m(2) resulted in an increase in adhesion from 4-8 nN to
      150-300 nN for tips with radii of 50-150 nm. The interfacial surface energy for
      identical nonpolar surface groups of SAMs was found not to exceed 2 mJ/m(2). An
      analysis of adhesion data suggests that the solvent was fully excluded from the
      zone of contact between functional groups on the tip and sample. With a nonpolar
      SAM, the force of adhesion increased monotonically in mixed solvents of higher
      water content; whereas, with a polar SAM (one having a hydrogen bonding
      component), higher water content led to decreased adhesion. The intermolecular
      force components theory was used for the interpretation of adhesion force
      measurements in polar solvents. Competition between hydrogen bonding within the
      solvent and hydrogen bonding of surface groups and the solvent was shown to
      provide the main contribution to adhesion forces. We demonstrate how the trends
      in the magnitude of the adhesion forces for chemically heterogeneous systems
      (solvents and surfaces) measured with CFM can be quantitatively rationalized
      using the surface tension components approach. For epoxy polymer, inelastic
      deformations also contributed heavily to measured adhesion forces.

PMID- 12197761
TI  - 13C NMR investigation of solid-state polymorphism in 10-deacetyl baccatin III.
AB  - To investigate the origins of solid-state NMR shift differences in polymorphs,
      carbon NMR chemical shift tensors are measured for two forms of solid 10-deacetyl
      baccatin III: a dimethyl sulfoxide (DMSO) solvate and an unsolvated form. A
      comparison of ab initio computed tensors that includes and omits the DMSO
      molecules demonstrates that lattice interactions cannot fully account for the
      shift differences in the two forms. Instead, conformational differences in the
      cyclohexenyl, benzoyl, and acetyl moieties are postulated to create the
      differences observed. X-ray analysis of six baccatin III analogues supports the
      suggested changes in the cyclohexenyl and benzoyl systems. The close statistical
      match of the (13)C chemical shifts of both polymorphic forms with those
      calculated using the X-ray geometry of 10-deacetyl baccatin III supports the
      contention that the B, C, and D rings are fairly rigid. Therefore, the observed
      tensor differences appear to arise primarily from conformational variations in
      ring substituents and the cyclohexenyl ring.

PMID- 12197763
TI  - Ultrafast UV pump/IR probe studies of C-H activation in linear, cyclic, and aryl
      hydrocarbons.
AB  - The photochemical C-H activation reactions of eta(3)-TpRh(CO)(2) (Tp = HB-Pz(3),
      Pz = 3,5-dimethylpyrazolyl) and CpRh(CO)(2) (Cp = C(5)H(5)) have been studied in
      a series of linear, cyclic, and aromatic hydrocarbon solvents on a femtosecond to
      microsecond time scale. These results have revealed that the structure of the
      hydrocarbon substrate affects the final C-H bond activation step, which is in
      accordance with the known preference of bond activation toward primary C-H sites.
      In the case of aromatic C-H activation, the reaction is divided into parallel
      channels involving sigma- and pi-solvated intermediates. Results for the
      analogous CpRh(CO)(2) molecule have shown that the coordination of the
      cyclopentadienyl ligand does not play a direct role in the dynamics of the
      reaction, in contrast to the C-H activation mechanism observed in eta(3)
      TpRh(CO)(2) studies.

PMID- 12197762
TI  - A nanoscale optical biosensor: sensitivity and selectivity of an approach based
      on the localized surface plasmon resonance spectroscopy of triangular silver
      nanoparticles.
AB  - Triangular silver nanoparticles ( approximately 100 nm wide and 50 nm high) have
      remarkable optical properties. In particular, the peak extinction wavelength,
      lambda(max) of their localized surface plasmon resonance (LSPR) spectrum is
      unexpectedly sensitive to nanoparticle size, shape, and local ( approximately 10
      30 nm) external dielectric environment. This sensitivity of the LSPR lambda(max)
      to the nanoenvironment has allowed us to develop a new class of nanoscale
      affinity biosensors. The essential characteristics and operational principles of
      these LSPR nanobiosensors will be illustrated using the well-studied biotin
      streptavidin system. Exposure of biotin-functionalized Ag nanotriangles to 100 nM
      streptavidin (SA) caused a 27.0 nm red-shift in the LSPR lambda(max). The LSPR
      lambda(max) shift, DeltaR/DeltaR(max), versus [SA] response curve was measured
      over the concentration range 10(-)(15) M < [SA] < 10(-)(6) M. Comparison of the
      data with the theoretical normalized response expected for 1:1 binding of a
      ligand to a multivalent receptor with different sites but invariant affinities
      yielded approximate values for the saturation response, DeltaR(max) = 26.5 nm,
      and the surface-confined thermodynamic binding constant K(a,surf) = 10(11) M(
      )(1). At present, the limit of detection (LOD) for the LSPR nanobiosensor is
      found to be in the low-picomolar to high-femtomolar region. A strategy to amplify
      the response of the LSPR nanobiosensor using biotinylated Au colloids and thereby
      further improve the LOD is demonstrated. Several control experiments were
      performed to define the LSPR nanobiosensor's response to nonspecific binding as
      well as to demonstrate its response to the specific binding of another protein.
      These include the following: (1) electrostatic binding of SA to a nonbiotinylated
      surface, (2) nonspecific interactions of prebiotinylated SA to a biotinylated
      surface, (3) nonspecific interactions of bovine serum albumin to a biotinylated
      surface, and (4) specific binding of anti-biotin to a biotinylated surface. The
      LSPR nanobiosensor provides a pathway to ultrasensitive biodetection experiments
      with extremely simple, small, light, robust, low-cost instrumentation that will
      greatly facilitate field-portable environmental or point-of-service medical
      diagnostic applications.

PMID- 12197764
TI  - Statistical and theoretical investigations on the directionality of nonbonded
      S...O interactions. Implications for molecular design and protein engineering.
AB  - Weak nonbonded interactions between a divalent sulfur (S) atom and a main-chain
      carbonyl oxygen (O) atom have recently been characterized in proteins. However,
      they have shown distinctly different directional propensities around the O atom
      from the S...O interactions in small organic compounds, although the linearity of
      the C-S...O or S-S...O atomic alignment was commonly observed. To elucidate the
      observed discrepancy, a comprehensive search for nonbonded S.O interactions in
      the Cambridge Structural Database (CSD) and MP2 calculations on the model
      complexes between dimethyl disulfide (CH(3)SSCH(3)) and various carbonyl
      compounds were performed. It was found that the O atom showed a strong intrinsic
      tendency to approach the S atom from the backside of the S-C or S-S bond (in the
      sigma(S) direction). On the other hand, the S atom had both possibilities of
      approach to the carbonyl O atom within the same plane (in the n(O) direction) and
      out of the plane (in the pi(O) direction). In the case of S...O(amide)
      interactions, the pi(O) direction was significantly preferred as observed in
      proteins. Thus, structural features of S...O interactions depend on the type of
      carbonyl groups involved. The results suggested that S.O interactions may control
      protein structures to some extent and that the unique directional properties of
      S...O interactions could be applied to molecular design.

PMID- 12197765
TI  - Hydrogen bonding in high-resolution protein structures: a new method to assess
      NMR protein geometry.
AB  - An analysis of backbone hydrogen bonds has been performed on nine high-resolution
      protein X-ray crystal structures. Backbone hydrogen-bond geometry is compared in
      the context of X-ray crystal structure resolution. A strong correlation between
      the hydrogen-bond distance, R(HO), and the hydrogen-bond angle, theta(NHO), is
      observed when the X-ray crystal structure resolution is <1.00 A. Ab initio
      calculations were performed to substantiate these results. The angle and distance
      limits found in our correlation for the backbone hydrogen-bond geometry can be
      used to evaluate the quality of protein structures and for further NMR structure
      refinement.

PMID- 12197766
TI  - Bladder carcinoma cell line ECV304 is not a model system for endothelial cells.

PMID- 12197768
TI  - A method for purifying enteric glia from rat myenteric plexus.
AB  - The enteric nervous system is a large and complex division of the peripheral
      nervous system. The glia associated with it share some characteristics with the
      olfactory-ensheathing glia, astrocytes and Schwann cells. To facilitate studies
      of rat enteric glia, we have developed a method for preparing them in large
      quantities with a high degree of homogeneity. The enteric glia were isolated from
      the small intestine of Wistar rats by enzymatic digestion with dispase. The cell
      isolate was added to a mitotically arrested layer of 3T3 cells. Subsequent
      separation of the enteric glia from the 3T3 cells was done enzymatically, with
      unavoidable loss of many enteric glia and potential contamination of enteric glia
      cultures with the 3T3 cells. Therefore, 3T3 cells were cultured in Nunc 0.2
      microm tissue culture inserts that could be readily removed from the wells when
      no longer needed. There was no loss of the enteric glia. The cultures consisted
      entirely of GFAP-labeled cells, presumptive enteric glia. This method permits the
      culturing of large numbers of highly purified enteric glia without the use of
      expensive growth factors and complement-mediated cytolysis.

PMID- 12197769
TI  - Spontaneous differentiation of porcine and bovine embryonic stem cells (epiblast)
      into astrocytes or neurons.
AB  - The culture of porcine or bovine epiblasts, i.e., embryonic stem cells, on STO
      feeder cells resulted in their spontaneous differentiation into multiple cell
      types that were subsequently isolated as separate cell lines. Some of these cell
      lines were "neuron-like" in morphology. Immunofluorescent analysis of two porcine
      epiblast-derived cell lines demonstrated that the cells were positive for the
      expression of vimentin and the glial fibrillary acidic protein (GFAP). Because of
      their stellate morphology and lack of neurofilament expression, it is possible
      that the cells are type 2 astrocytes. Similar analysis of a bovine epiblast
      derived cell line showed that the cells were positive for vimentin but that they
      did not express GFAP. However, a few cells within the population expressed
      neurofilaments and alpha-internexin. It is possible that the bovine cells are
      neural precursor cells. The results confirm and extend the demonstrated in vitro
      pluripotency of porcine and bovine epiblast cultures and provide evidence for an
      in vitro model of embryonic neuroectoderm development.

PMID- 12197770
TI  - The specificity of phenotypic induction of mouse and human stem cells by
      signaling complexes.
AB  - Controlling the specific differentiation of stem cells (SCs) is a goal sought by
      many because of the benefits it would yield for repair or replacement of damaged
      tissues and organs. We report the discovery of signaling complexes and describe
      their use in predictably guiding the differentiation of mouse and human SCs. The
      signaling complexes (Signal-plexes [S-ps]) induce mouse and human SCs to express
      specific phenotypes. The S-ps have been used to identify a new source of human
      SCs (Hu abba-1) and have been shown to induce differentiation of multiple tissue
      specific phenotypes selectively in mouse pluripotent embryonic cells as well as
      in Hu abba-1 cells. Endocrine and exocrine pancreas, liver, lung, kidney, heart,
      cartilage, bone, and other cell types have been induced in SCs by S-ps, as shown
      by morphology, immunostaining, enzyme-linked immunosorbent assay, and reverse
      transcriptase-polymerase chain reaction analysis.

PMID- 12197771
TI  - Lipotropes regulate bcl-2 gene expression in the human breast cancer cell line,
      MCF-7.
AB  - Lipotropes, a methyl group containing nutrients, including choline, methionine,
      folic acid, and vitamin B(12), are essential nutrients for humans. They are
      important methyl donors that interact in the metabolism of one-carbon units and
      are essential for the synthesis and methylation of deoxyribonucleic acid. The
      purpose of this study was to examine the effects of excess lipotropes on the
      growth of a human breast cancer cell line, MCF-7, and normal mammary cells, MCF
      10A, in culture. Both cell lines were grown in basal culture medium for 24 h and
      then switched to medium supplemented with 50 times the amount of each lipotrope
      as basal culture medium (control). Although there were no significant differences
      in growth between treatments in either cell line, gene array and Northern
      analysis revealed that expression of bcl-2 was decreased in lipotrope-treated MCF
      7 cells. The ability to induce tumor cell death could have many uses in the
      prevention and treatment of cancer. Bcl-2 regulates apoptosis and has been shown
      to directly affect the sensitivity of cancer cells to chemotherapy agents, and it
      is suggested that strategies designed to block Bcl-2 might prove useful in
      sensitizing tumor cells to chemotherapy-induced apoptosis. This study shows that
      although excess lipotropes do not inhibit the growth of breast cancer cells, they
      can down-regulate the bcl-2 gene, suggesting that lipotropes may increase the
      susceptibility of breast cancer cells to anticancer drugs.

PMID- 12197772
TI  - Isolation and culture of rat microvascular endothelial cells.
AB  - The purpose of this study is to identify the separation techniques that result in
      pure cultures of rat microvascular endothelial cells (MECs). A multistep process
      is used to optimize the separation of the cells from rat epididymal fat pads,
      obtaining as pure a culture as possible within a relatively short processing
      time. The process initially employs the digestion, filtration, and density
      gradient separation steps. We further describe the use of an attachment phase
      that allows the differential adherence of contaminating cell types.
      Immunomagnetic purification is the final step in the process and is performed
      using anti-PECAM-1 (CD31) monoclonal antibody-labeled DynaBeads.

PMID- 12197773
TI  - A countermeasure to ameliorate immune dysfunction in in vitro simulated
      microgravity environment: role of cellularnucleotide nutrition.
AB  - Considerable evidence suggests that space travelers are immunosuppressed,
      presumably by microgravity environmental stresses, putting them at risk for
      adverse effects, such as opportunistic infections, poor wound healing, and
      cancer. The purpose of this study was to examine the role and mechanisms of
      nucleotide (NT) supplementation as a countermeasure to obviate immunosuppression
      during space travel. The in vitro rotary cell culture system, a bioreactor (BIO),
      was used to simulate the effect of microgravity and to isolate the neuroendocrine
      effects inherent to in vitro models. The splenocytes from normal mice were
      cultured in BIO and control tissue culture (TC) flasks with and without
      phytohemagglutinin (PHA) for mitogen assays. The culture medium was then
      supplemented with various concentrations of a nucleosides-nucleotides mixture (NS
      + NT), inosine, and uridine. Cytokines interleukin (IL)-1beta, IL-2, IL-3, tumor
      necrosis factor-alpha, and interferon (IFN)-gamma were measured from the
      supernatant by enzyme-linked immunosorbent assay. In the PHA-stimulated cultures
      the cellular proliferation in the BIO was significantly decreased as compared
      with the TC flask cells. BIO-cultured cells in the presence of NS + NT maintained
      mitogen responses similar to the control TC flask cells. The maintenance of the
      mitogen response in BIO was observed by the supplementation of uridine and not of
      inosine. These results are in agreement with our earlier results from unit
      gravity experiments that showed that pyrimidines are more effective in pleiogenic
      immunoprotection to hosts. Cytokines IL-1beta, IL-2, and IFN-gamma in the BIO
      supernatants of cells cultured in the presence of NS + NT had a significantly
      higher response than the control vessel. Thus, supplemental NT, especially
      pyrimidines, can confer immune protection and enhance cytokine responses during
      space travel.

PMID- 12197775
TI  - An in vitro model of the back of the eye for studying retinal pigment epithelial
      choroidal endothelial interactions.
AB  - At the back of the eye, the outermost cell layer of the retina, the pigmented
      epithelium, lies against a basement membrane that is adjacent to the choroidal
      vessels that supply the outer sensory retina. During pathogenesis, these
      interfaces become damaged, and the homeostatic balance between the retinal
      pigment epithelium (RPE) and the choroidal vessels becomes disrupted, leading to
      choroidal neovascularization and blindness. To study the cell interactions at the
      back of the eye, we have used a coculture system in which a stable RPE monolayer
      has been cultured on a transwell insert and placed over a collagen gel sandwich
      into which choroidal endothelial cells (CECs) have been seeded. RPE cells have
      been stimulated by an inflammatory cytokine, interleukin-1 (IL-1beta), and the
      ability of the underlying choroidal endothelium to form vascular tubes has been
      tested. IL-1beta stimulation of the RPE insert increased the number of tubes
      formed by CECs in the gel as early as 3 d. By 7 d, tubes began to regress. Both
      IL-8 and monocyte chemotactic protein-1 (MCP-1) were found to be secreted in
      greater amounts in stimulated RPE. Because MCP-1 is also a chemokine for
      monocytes, which in turn secrete angiogenic factors, monocytes were added to the
      upper surface of the choroidal gel sandwich and then incubated with the
      stimulated RPE insert as above. By day 7, more tubes formed and there was no
      regression over the experimental time period. The versatility of this model has
      been illustrated in that both RPE and CECs can be cultured in a more natural
      construct and their molecular interactions tested by physiologically altering one
      cell type and not the other.

PMID- 12197774
TI  - Characterization of glucose transport by cultured rabbit kidney proximal
      convoluted and proximal straight tubule cells.
AB  - Rabbit kidney proximal convoluted tubule (RPCT) and proximal straight tubule
      (RPST) cells were independently isolated and cultured. The kinetics of the sodium
      dependent glucose transport was characterized by determining the uptake of the
      glucose analog alpha-methylglucopyranoside. Cell culture and assay conditions
      used in these experiments were based on previous experiments conducted on the
      renal cell line derived from the whole kidney of the Yorkshire pig (LLC-PK1).
      Results indicated the presence of two distinct sodium-dependent glucose
      transporters in rabbit renal cells: a relatively high-capacity, low-affinity
      transporter (V(max) = 2.28 +/- 0.099 nmoles/mg protein min, Km = 4.1 +/- 0.27 mM)
      in RPCT cells and a low-capacity, high-affinity transporter (V(max) = 0.45 +/-
      0.076 nmoles/mg protein min, K(m) = 1.7 +/- 0.43 mM) in RPST cells. A relatively
      high-capacity, low-affinity transporter (V(max) = 1.68 +/- 0.215 nmoles/mg
      protein min, Km = 4.9 +/- 0.23 mM) was characterized in LLC-PK1 cells. Phlorizin
      inhibited the uptake of alpha-methylglucopyranoside in proximal convoluted,
      proximal straight, and LLC-PK1 cells by 90, 50, and 90%, respectively. Sodium
      dependent glucose transport in all three cell types was specific for hexoses.
      These data are consistent with the kinetic heterogeneity of sodium-dependent
      glucose transport in the S1-S2 and S3 segments of the mammalian renal proximal
      tubule. The RPCT-RPST cultured cell model is novel, and this is the first report
      of sodium-dependent glucose transport characterization in primary cultures of
      proximal straight tubule cells. Our results support the use of cultured
      monolayers of RPCT and RPST cells as a model system to evaluate segment-specific
      differences in these renal cell types.

PMID- 12197777
TI  - Regression models for overdispersed jejunal surviving crypts data.
AB  - The dose-response model concerns to establish a relationship between a dose and
      the magnitude of the response produced by the dose. A common complication in the
      dose-response model for jejunal crypts cell surviving data is overdispersion,
      where the observed variation exceeds that predicted from the binomial
      distribution. In this study, two different methods for analyzing jejunal crypts
      cell survival after regimens of several fractions are contrasted and compared.
      One method is the logistic regression approach, where the numbers of surviving
      crypts are predicted by the logistic function of a single dose of radiation. The
      other one is the transform-both-sides approach, where the arcsine transformation
      family is applied based on the first-order variance-stabilizing transformation.
      This family includes the square root, arcsine, and hyperbolic arcsine
      transformations, which have been used for Poisson, binomial, and negative
      binomial count data, as special cases. These approaches are applied to a data set
      from radiobiology. Simulation study indicates that the arcsine transformation
      family is more efficient than the logistic regression when there exists moderate
      overdispersion.

PMID- 12197776
TI  - Rb localization and phosphorylation kinetics correlate with the cellular
      phenotype of cultured breast adenocarcinoma cells.
AB  - Retinoblastoma protein (Rb) expression has been correlated with state of
      differentiation, proliferation rate, and metastatic potential in breast
      adenocarcinomas and established cell lines. These observations, based on
      immunoreactivity of total Rb rather than hypophosphorylated protein, do not
      address the relationship between functional Rb and indicators of an aggressive
      transformed cellular phenotype. We hypothesized that the distribution of
      functional Rb and the kinetics of Rb phosphorylation would differ between cell
      lines representing immortalized mammary epithelium (MCF10A), differentiated
      nonmetastatic mammary adenocarcinoma (MCF-7), and poorly differentiated, highly
      metastatic mammary adenocarcinoma (MDA-MB-231) and that these differences would
      be informative of the cellular phenotype. Direct immunofluorescence microscopy
      was used to compare qualitatively the subcellular localization of total and
      hypophosphorylated Rb protein in synchronized and asynchronous cells. This
      technique was also used to quantitatively assess the amounts of
      hypophosphorylated Rb throughout the cell cycle in these representative cell
      lines. Total Rb stained more prominently than hypophosphorylated Rb in the
      nucleus of all asynchronous cells. Rb phosphorylation was more rapid in MCF-7
      cells than in MCF10A cells, whereas Rb dephosphorylation appeared deregulated in
      MDA-MB-231 cells. We conclude that assessment of hypophosphorylated Rb may be
      more useful than assessment of total Rb for the evaluation of transformed breast
      adenocarcinoma phenotypes.

PMID- 12197780
TI  - Good science or good marketing?

PMID- 12197781
TI  - Nonalcoholic fatty liver disease: relationship to insulin sensitivity and
      oxidative stress. Treatment approaches using vitamin E, magnesium, and betaine.
AB  - Nonalcoholic steatotic hepatitis (NASH), the most prevalent form of progressive
      liver disease in the United States, is considered to be a manifestation of
      insulin resistance syndrome. There is increasing evidence that steatosis in NASH
      is a result of the pathology in fat metabolism occurring in obesity and insulin
      resistance. For steatosis to progress to necroinflammation and fibrosis, however,
      the theory of mitochondrial oxidative-stress induced cellular damage is receiving
      wide acceptance. Treatment approaches that address these etiologies are reviewed:
      betaine, magnesium, and vitamin E.

PMID- 12197782
TI  - Autism, an extreme challenge to integrative medicine. Part: 1: The knowledge
      base.
AB  - Autism, archetype of the autistic spectrum disorders (ASD), is a
      neurodevelopmental disorder characterized by socially aloof behavior and
      impairment of language and social interaction. Its prevalence has surged in
      recent years. Advanced functional brain imaging has confirmed pervasive
      neurologic involvement. Parent involvement in autism management has accelerated
      understanding and treatment. Often accompanied by epilepsy, cognitive deficits,
      or other neurologic impairment, autism manifests in the first three years of life
      and persists into adulthood. Its etiopathology is poorly defined but likely
      multifactorial with heritability playing a major role. Prenatal toxic exposures
      (teratogens) are consistent with autism spectrum symptomatology. Frequent
      vaccinations with live virus and toxic mercurial content (thimerosal) are a
      plausible etiologic factor. Autistic children frequently have abnormalities of
      sulfoxidation and sulfation that compromise liver detoxification, which may
      contribute to the high body burden of xenobiotics frequently found. Frequent
      copper-zinc imbalance implies metallothionein impairment that could compound the
      negative impact of sulfur metabolism impairments on detoxification and on
      intestinal lining integrity. Intestinal hyperpermeability manifests in autistic
      children as dysbiosis, food intolerances, and exorphin (opioid) intoxication,
      most frequently from casein and gluten. Immune system abnormalities encompass
      derangement of antibody production, skewing of T cell subsets, aberrant cytokine
      profiles, and other impairments consistent with chronic inflammation and
      autoimmunity. Coagulation abnormalities have been reported. Part 2 of this review
      will attempt to consolidate progress in integrative management of autism, aimed
      at improving independence and lifespan for people with the disorder.

PMID- 12197778
TI  - Sphingosine-1-phosphate stimulates human Caco-2 intestinal epithelial
      proliferation via p38 activation and activates ERK by an independent mechanism.
AB  - Sphingosine-1-phosphate (S-1-P) has been identified as an extracellular mediator
      and an intracellular second messenger that may modulate cell motility, adhesion,
      proliferation, and differentiation and cancer cell invasion. Widely distributed,
      S-1-P is most abundant in the intestine. Although S-1-P is likely to modulate
      various intracellular pathways, activation of the mitogen-activated protein
      kinases (MAPKs) such as extracellular signal-regulated kinase 1 (ERK1), ERK2, and
      p38 is among the best-characterized S-1-P effects. Because the MAPKs regulate
      proliferation, we hypothesized that S-1-P might stimulate intestinal epithelial
      cell proliferation by MAPK activation. Human Caco-2 intestinal epithelial cells
      were cultured on a fibronectin matrix because fibronectin is an important
      constituent of the gut mucosal basement membrane. We assessed ERK1, ERK2, and p38
      activation by Western blotting with antibodies specific for their active forms
      and proliferation by Coulter counting at 24 h. Specific MAP kinase kinase (MEK)
      and p38 inhibitors PD98059 (20 microM) and SB202190 and SB203580 (10 and 20
      microM) were used to probe the role of ERK and p38 in S-1-P-mediated
      proliferation. Three or more similar studies were pooled for the analysis. S-1-P
      stimulated Caco-2 proliferation and dose-responsively activated ERK1, ERK2, and
      p38. Proliferation peaked at 5 microM, yielding a cell number 166.3 +/- 2.7% of
      the vehicle control (n = 6, P < 0.05). S-1-P also maximally stimulated ERK1,
      ERK2, and p38 at 5 microM, to 164.4 +/- 19.9%, 232.2 +/- 38.5%, and 169.2 +/-
      20.5% of the control, respectively. Although MEK inhibition prevented S-1-P
      activation of ERK1 and ERK2 and slightly but significantly inhibited basal Caco-2
      proliferation, MEK inhibition did not block the S-1-P mitogenic effect. However,
      pretreatment with 10 microM SB202190 or SB203580 (putative p38 inhibitors)
      attenuated the stimulation of proliferation by S-1-P. Twenty micromolars of
      SB202190 or SB203580 completely blocked the mitogenic effect of S-1-P. Ten to
      twenty micromolars of SB202190 and SB203580 also dose-dependently ablated the
      effects of 5 microM S-1-P on heat shock protein 27 accumulation, a downstream
      consequence of p38 MAPK activation. Consistent with the reports in some other
      cell types, S-1-P appears to activate ERK1, ERK2, and p38 and to stimulate
      proliferation. However, in contrast to the mediation of the S-1-P effects in some
      other cell types, S-1-P appears to stimulate human intestinal epithelial
      proliferation by activating p38. ERK activation by S-1-P is not required for its
      mitogenic effect.

PMID- 12197783
TI  - Soy and its isoflavones: a review of their effects on bone density.
AB  - Menopausal hormone decline contributes significantly to the risk of osteoporosis.
      Therapies for treating osteoporosis, such as hormone replacement therapy
      (estrogen or combination estrogen-progestins), inhibit bone resorption. Both
      animal and human studies demonstrate phytoestrogenic soy isoflavones favorably
      impact bone health. The exact mechanism is still unclear. Additional research is
      needed to determine if isoflavones are an effective alternative to hormone
      replacement therapy for the prevention and treatment of osteoporosis. This paper
      reviews in vitro, animal, and human studies involving isoflavones and bone
      health.

PMID- 12197784
TI  - Effect of ceramic-impregnated "thermoflow" gloves on patients with Raynaud's
      syndrome: randomized, placebo-controlled study.
AB  - OBJECTIVE: To determine the efficacy of ceramic impregnated gloves in the
      treatment of Raynaud's syndrome. DESIGN: Double-blind, placebo-controlled study.
      SETTING: Teaching hospital outpatient clinic. PARTICIPANTS: Ninety-three patients
      meeting the "Pal" criteria for Raynaud's syndrome. INTERVENTIONS: Treatment
      period of three months with use of ceramic-impregnated gloves. MAIN OUTCOME
      MEASURES: Primary end points: Pain visual analogue scale ratings and diary;
      Disabilities of the Arm, Shoulder, Hand questionnaire; Jamar grip strength;
      Purdue board test of hand dexterity. Secondary end points: Infrared skin
      temperature measurements; seven-point Likert scale rating of treatment. RESULTS:
      In 60 participants with complete data, improvements were noted in the visual
      analogue scale rating (p=0.001), DASH score (p=0.001), Jamar grip strength
      (p=0.002), infrared skin fingertip temperature (p=0.003), Purdue hand dexterity
      test (p=0.0001) and the Likert scale (p=0.001) with ceramic gloves over the
      placebo cotton gloves. CONCLUSION: The ceramic-impregnated "thermoflow" gloves
      have a clinically important effect in Raynaud's syndrome.

PMID- 12197785
TI  - Calcium-D-glucarate.
AB  - Calcium-D-glucarate is the calcium salt of D-glucaric acid, a substance produced
      naturally in small amounts by mammals, including humans. Glucaric acid is also
      found in many fruits and vegetables with the highest concentrations to be found
      in oranges, apples, grapefruit, and cruciferous vegetables. Oral supplementation
      of calcium-D-glucarate has been shown to inhibit beta-glucuronidase, an enzyme
      produced by colonic microflora and involved in Phase II liver detoxification.
      Elevated beta-glucuronidase activity is associated with an increased risk for
      various cancers, particularly hormone-dependent cancers such as breast, prostate,
      and colon cancers. Other potential clinical applications of oral calcium-D
      glucarate include regulation of estrogen metabolism and as a lipid-lowering
      agent.

PMID- 12197786
TI  - Lactobacillus sporogenes.
AB  - Lactobacillus sporogenes is a gram-positive, spore-forming, lactic-acid producing
      bacillus. It was originally isolated and described in 1933. The organism requires
      a complex mixture of organic substrates for growth, including fermentable
      carbohydrates and peptides. It has been used clinically for gut dysbiosis,
      hyperlipidemia, aphthous stomatitis, and vaginitis.

PMID- 12197787
TI  - Obesity, nutrition, and physical activity--call for papers.

PMID- 12197788
TI  - "Home-Sick": the effect of a child's environment on health.

PMID- 12197789
TI  - The evaluation of young febrile children for occult bacteremia: time to
      reevaluate our approach?

PMID- 12197790
TI  - Hospitalists and residency medical education: measured improvement.

PMID- 12197791
TI  - Lead poisoning and asthma: an examination of comorbidity.
AB  - OBJECTIVES: To determine the comorbidity of lead poisoning and asthma in urban
      children, and to examine associated clinical factors. METHODS: One-hundred-one
      patients at an inner-city clinic with blood lead levels (BLLs) of 25 microg/dL or
      higher (> or =1.2 micromol/L) (BLL25 group) were randomly selected from a
      tracking lead database and matched on age, sex, and primary language to 101
      randomly selected patients with a first BLL recorded in the database of lower
      than 5 microg/dL (<0.2 micromol/L) (BLL5 group) and no subsequent BLLs of 10
      microg/dL or higher (> or =0.5 micromol/L). Medical records were reviewed to
      determine diagnosis or symptoms of asthma or wheezing at any visit, immunization
      status, and number of visits. Analyses for matched pairs were conducted. RESULTS:
      The BLL25 and BLL5 groups did not differ on age at diagnostic BLL (26.6 months vs
      24.2 months), sex (54% male), or language (12% Spanish). The BLL25 and BLL5
      groups had a similar number of subjects with a diagnosis of asthma (6% vs 11%;
      odds ratio, 0.5; 95% confidence interval, 0.2-1.6); 26% of BLL25 and 34% of BLL5
      subjects had either a diagnosis or symptoms of asthma or wheezing (odds ratio,
      0.7; 95% confidence interval, 0.4-1.3). Subjects with BLL25 were more likely to
      have delayed immunization and a first clinic visit when older than subjects with
      BLL5. CONCLUSIONS: There was no increased likelihood of asthma diagnosis or
      symptoms among young children with lead poisoning. Children with lead poisoning
      also had delayed medical care. These data may help guide interventions aimed at
      preventing or reducing the impact of lead poisoning and asthma.

PMID- 12197792
TI  - Validity of children's food portion estimates: a comparison of 2 measurement
      aids.
AB  - BACKGROUND: Policy and clinical decisions regarding children's nutrition are
      often based on dietary intake estimates from self-reports. The accuracy of these
      estimates depends on memory of both the type of food eaten and the amount
      consumed. Although children's self-reports of food intake are widely used, there
      is little research on their ability to estimate food portions. OBJECTIVE: To
      assess the validity of children's estimates of the food portions they consume by
      means of 2 types of measurement aids: standard 2-dimensional food portion visuals
      and manipulative props. DESIGN: Randomized controlled trial. PARTICIPANTS: Fifty
      four African American girls aged 8 to 12 years. MAIN OUTCOME MEASURES: Girls were
      served a standard meal and actual intake was assessed by weighing food portions
      before and after the meal. On completion of the meal, dietitians collected food
      recalls and portion size estimates from the girls by means of both manipulative
      props and 2-dimensional food portion visuals, administered in a randomized order.
      RESULTS: Absolute value percentage differences between actual and estimated grams
      of food consumed averaged 58.0% (SD, 102.7%) for manipulative props and 32.8%
      (SD, 72.8%) for 2-dimensional food portion visuals. Spearman correlations between
      actual and estimated intakes with both portion size measurement aids were high
      (range, r = 0.56 to 0.79; all P<.001), with the exception of bread intake (r =
      0.16, P =.43). Correlations with actual intakes did not differ significantly
      between the 2 methods. CONCLUSIONS: Children's self-reported portion size
      estimates are appropriate for ranking children's relative intakes, but they
      result in sizable errors in quantitative estimates of food and energy intakes.
      Caution should be used in interpreting quantitative dietary intake estimates
      derived from children's self-reports.

PMID- 12197793
TI  - Effectiveness of an asthma management program for pediatric members of a large
      health maintenance organization.
AB  - OBJECTIVE: To assess the impact of an asthma management program on the dispensing
      of inhaled corticosteroids, hospitalizations, and emergency department (ED)
      visits on children, adolescents, and young adults. DESIGN: We used medical record
      and pharmacy data for the 18 months after initiation of a pilot asthma management
      program. Two intervention offices were matched with 2 control offices on
      pediatric volume, number of pediatricians or family practitioners, and specialist
      availability. SETTING: Primary care offices at Kaiser Permanente Colorado, in
      Denver and Boulder. PATIENTS: We identified 298 patients, 18 years or younger,who
      were listed in an asthma registry between February 1 and July 31, 1997, as having
      moderate or severe asthma. INTERVENTION: The Kaiser Permanente Colorado Asthma
      Care Management Program is an outpatient-based program that provides
      comprehensive evaluation, education, and follow-up to patients identified from an
      asthma registry or referred by providers. MAIN OUTCOME MEASURES: The proportion
      of patients who received more than 1 dispensing of inhaled corticosteroid during
      the observation period. Additional outcomes measured the proportion of patients
      with 1 or more hospitalizations or ED visits. RESULTS: A significantly greater
      proportion of patients from the intervention group received more than 1
      dispensing of inhaled corticosteroid compared with controls (relative risk [RR],
      1.41; 95% confidence interval [CI], 1.08-1.72). We found no significant
      difference in the proportion of patients who were hospitalized (RR, 1.37; 95% CI,
      0.48-3.71) or visited the ED (RR, 0.86; 95% CI, 0.49-1.40). CONCLUSIONS: The
      presence of an asthma management program may improve dispensing of inhaled
      corticosteroids to young patients with moderate or severe asthma, as recommended
      by national guidelines. This type of program may not have an effect on
      hospitalizations or ED visits.

PMID- 12197794
TI  - Effect of a pediatric hospitalist system on housestaff education and experience.
AB  - OBJECTIVE: To determine the effect of a pediatric hospitalist system on
      housestaff education and experience. SETTING: Free-standing academic children's
      hospital. Hospitalists were introduced in June 24, 1998, to supervise teaching
      and care on the general pediatric wards. METHODS: On 2 surveys, housestaff rated
      their skills, knowledge, and experiences on the wards (experiences survey), and
      the quality of teaching and supervision by attending physicians (attending
      survey). Responses before and after the introduction of the hospitalist system
      were compared using Wilcoxon nonparametric tests. RESULTS: Seventy-six (70%) of
      the 109 interns and 54 (62%) of the 87 senior residents responded to the
      experiences survey. Following introduction of the hospitalist system, the
      interns' mean overall rating of the general pediatrics wards rose from 4.1 to 4.7
      on a 5-point Likert scale (P =.01). Their ratings of comparison rotations did not
      change significantly. Interns' satisfaction with the educational experience (3.2
      to 3.5 of a 4-point Likert scale, P<.05), supervision, and quality of life on the
      pediatrics wards also improved significantly, as did their self-assessments of
      skills and knowledge related to general pediatrics training. Senior residents'
      ratings were generally unchanged. Three hundred seventy-one (63%) of the 593
      attending physicians' surveys were completed. Compared with nonhospitalist
      attendings, hospitalists were rated more effective role models (4.7 vs 4.5
      points, P<.05) and teachers (4.7 vs 4.4 points, P<.01). They were rated more
      knowledgeable (4.8 vs 4.5 of 5, P<.001) and accessible (4.7 vs 4.5 points,
      P<.05), involved housestaff more in the learning process (4.7 vs 4.4 points,
      P<.05), and gave better feedback (4.5 vs 4.2 points, P<.01). Hospitalists'
      bedside teaching, however, was rated lower (3.7 vs 4.2 points, P<.001).
      CONCLUSIONS: Overall, hospitalists were rated significantly higher as educators
      than were traditional attending physicians. Introduction of a hospitalist system
      was associated with improved intern experience and quality of life on general
      pediatrics wards, and with improved self-reported skills and knowledge in general
      pediatrics.

PMID- 12197795
TI  - The use of dextroamphetamine to treat obesity and hyperphagia in children treated
      for craniopharyngioma.
AB  - BACKGROUND: Obesity and attention difficulties are known complications following
      surgical treatment for craniopharyngioma. Treatments to date have been largely
      disappointing. OBJECTIVE: To examine the use of the central nervous system
      stimulant dextroamphetamine sulfate to regulate appetite and subsequent weight
      gain in children treated for craniopharyngioma. SETTING: A multidisciplinary
      clinic specializing in pediatric brain tumors. PATIENTS: Five consecutive
      patients with significant weight gain and poor attention following surgical
      treatment for craniopharyngioma were selected for the study. INTERVENTION:
      Children enrolled in the study were treated with dextroamphetamine, and growth,
      laboratory, and behavioral assessments were conducted for 24 months. RESULTS:
      Mean +/- SD body mass index (weight in kilograms divided by height in meters
      squared) increased from 21 +/- 3.5 before the operation to 32 +/- 2.8 by the
      start of the protocol. Body mass indices remained stable throughout the protocol.
      No changes were observed in insulin levels or caloric intake, but the children
      were more active when taking dextroamphetamine. Parents noted a significant
      improvement in hyperactivity (mean +/- SD, 1.2 +/- 0.4 to 0.6 +/- 0.2; P =.05),
      scored with the Conners Parent and Teacher Rating Scales. Teachers noted a
      similar improvement. CONCLUSIONS: During dextroamphetamine treatment, weight gain
      stabilized in children who had experienced obesity following surgical resection
      for craniopharyngioma. In addition, parents and teachers noted significant
      improvements in children's overall activity and attention. Further studies are
      needed to determine if the improvements are stable and if earlier intervention
      can prevent the initial obesity.

PMID- 12197796
TI  - Acute kidney failure: a pediatric experience over 20 years.
AB  - BACKGROUND: Acute kidney failure in children is a catastrophic, life-threatening
      event. OBJECTIVE: To compare and contrast 2 decades of data, analyzing the
      underlying causes, associated multiple organ system failures, outcome of dialysis
      procedures, and other variables of interest. DESIGN: Retrospective examination of
      clinical data collected between January 1, 1979, and December 31, 1998. SETTING:
      Regional health care center in the mid-Atlantic area. PARTICIPANTS: Two hundred
      twenty-eight patients, aged from 1 day to 18 years, had acute kidney failure and
      were referred to a pediatric nephrology service. MAIN OUTCOME MEASURES:
      Characteristics, percentage of mortality, intensive care unit admission,
      procedures, and other variables and causes of acute renal failure. RESULTS: The
      total number of cases analyzed represented 7% of all patients presented to the
      pediatric nephrology service. Sex distribution, ethnicity, and survival
      statistics were unchanged between both decades. The overall survival rate was
      73%. One hundred fifty-four patients (68%) were admitted to the pediatric
      intensive care unit. The following 106 acute extracorporeal procedures were
      performed on 93 patients (41%): 12 patients received extracorporeal membrane
      oxygenation, 52 patients underwent peritoneal dialysis, 32 underwent
      hemodialysis, 3 patients received continuous venovenous hemofiltration, and 7
      patients received continuous arteriovenous hemofiltration. Sepsis and burns,
      other leading causes of acute renal failure in the first decade, are replaced in
      the second decade by hematologic-oncologic complications and pulmonary failure.
      CONCLUSIONS: Acute kidney failure following repair of cardiac lesions remains
      unchanged as a leading risk factor of mortality in both decades. Three organ
      system failures were associated with more than a 50% mortality rate. Predialysis
      low serum albumin concentrations emerged as a significant copredictor of
      mortality.

PMID- 12197797
TI  - Pediatric and young adult exposure to chemiluminescent glow sticks.
AB  - BACKGROUND: Although chemiluminescent plastic rods, commonly called "glow sticks"
      or "light sticks," are typically considered to be minimally toxic or nontoxic,
      published data about exposure to these products are scarce. OBJECTIVES: To test
      our hypothesis that exposure to chemiluminescent products is unlikely to result
      in significant morbidity or mortality and to describe factors associated with
      exposure by reviewing reports to our urban poison control center of human
      exposure to chemiluminescent products. METHODS: Pediatric and young adult
      exposure to chemiluminescent products reported between January 1, 2000, and April
      1, 2001, to our poison control center were evaluated with regard to demographic
      group, type of product involved, circumstances of exposure, symptoms, and
      management. RESULTS: Reported routes of exposure (n = 118) included ingestion (n
      = 108), ocular (n = 9), and dermal exposure (n = 1). Only patients exposed to
      chemiluminescent fluid from a leaking container reported symptoms (n = 27).
      Symptoms were limited to transient irritation of the exposure site, and no
      systemic toxicity occurred. All adults (n = 4) inadvertently ruptured or
      swallowed intact light sticks while at a dance club or dance party. Most exposure
      and all adult exposure occurred on holidays or weekends. CONCLUSIONS: Most
      incidences of exposure to chemiluminescent products involve asymptomatic
      ingestion of fluid that leaks from glow sticks or ingestion of an intact glow
      stick. Symptoms occur after exposure to chemiluminescent fluid and consist of
      transient irritation at the site of exposure. The clustering of reported exposure
      on weekends and in dance clubs and parties coupled with a lack of occupational or
      workplace exposure suggest that recreational use is a major contributory factor.
      Exposure to chemiluminescent products infrequently resulted in symptoms and the
      symptoms reported were minor. Exposure to chemiluminescent products as described
      is unlikely to cause significant morbidity or mortality.

PMID- 12197798
TI  - Utility of the serum C-reactive protein for detection of occult bacterial
      infection in children.
AB  - OBJECTIVE: To assess the utility of serum C-reactive protein (CRP) as a screen
      for occult bacterial infection in children. METHODS: Febrile children ages 3 to
      36 months who visited an urban children's hospital emergency department and
      received a complete blood cell count and blood culture as part of their
      evaluation were prospectively enrolled from February 2, 2000, through May 30,
      2001. Informed consent was obtained for the withdrawal of an additional 1-mL
      aliquot of blood for use in CRP evaluation. Logistic regression and receiver
      operator characteristic (ROC) curves were modeled for each predictor to identify
      optimal test values, and were compared using likelihood ratio tests. RESULTS: Two
      hundred fifty-six patients were included in the analysis, with a median age of
      15.3 months (range, 3.1-35.2 months) and median temperature at triage 40.0
      degrees C (range, 39.0 degrees C-41.3 degrees C). Twenty-nine (11.3%) cases of
      occult bacterial infection (OBI) were identified, including 17 cases of
      pneumonia, 9 cases of urinary tract infection, and 3 cases of bacteremia. The
      median white blood cell count in this data set was 12.9 x 10(3)/ micro L
      [corrected] (range, 3.6-39.1 x10(3)/ micro L) [corrected], the median absolute
      neutrophil count (ANC) was 7.12 x 10(3)/L [corrected] (range, 0.56-28.16
      x10(3)/L) [corrected], and the median CRP level was 1.7 mg/dL (range, 0.2-43.3
      mg/dL). The optimal cut-off point for CRP in this data set (4.4 mg/dL) achieved a
      sensitivity of 63% and a specificity of 81% for detection of OBI in this
      population. Comparing models using cut-off values from individual laboratory
      predictors (ANC, white blood cell count, and CRP) that maximized sensitivity and
      specificity revealed that a model using an ANC of 10.6 x10(3)/L [corrected]
      (sensitivity, 69%; specificity, 79%) was the best predictive model. Adding CRP to
      the model insignificantly increased sensitivity to 79%, while significantly
      decreasing specificity to 50%. Active monitoring of emergency department blood
      cultures drawn during the study period from children between 3 and 36 months of
      age showed an overall bacteremia rate of 1.1% during this period. CONCLUSIONS: An
      ANC cut-off point of 10.6 x10(3)/L [corrected] offers the best predictive model
      for detection of occult bacterial infection using a single test. The addition of
      CRP to ANC adds little diagnostic utility. Furthermore, the lowered incidence of
      occult bacteremia in our population supports a decrease in the use of diagnostic
      screening in this population.

PMID- 12197799
TI  - Behavioral correlates of television viewing in primary school children evaluated
      by the child behavior checklist.
AB  - BACKGROUND: Television is a source from which children gain information about
      life and experience different types of behavior. The Child Behavior Checklist
      (CBCL) has not been used thoroughly to evaluate the behavioral effects of
      television viewing on children. OBJECTIVE: To examine the competency and problem
      behavior correlates of television viewing in school-aged children using the CBCL.
      DESIGN: Cross-sectional survey. SETTING: Two randomly selected grade schools, one
      from a high-income district and the other from a low-income district.
      PARTICIPANTS: Students in grades 2 and 3 and their parents. MAIN OUTCOME
      MEASURES: A questionnaire on children's time spent watching television and
      engaging in other daily activities and the CBCL were sent to the parents of 888
      second- and third-grade students. RESULTS: Results of the questionnaire reported
      that the overall mean +/- SD daily television viewing time was 2.5 +/- 1.3 hours.
      Overall television viewing time had a negative correlation with social and school
      achievement (r = -0.17, P<.001 and r = 0.11, P =.03, respectively) subscale
      scores. Withdrawn (r = 0.11, P =.004), social problem (r = 0.14, P =.001),
      thought problem (r = 0.11, P =.03), attention problem (r = 0.20, P<.001),
      delinquent behavior (r = 0.12, P<.001), aggressive behavior (r = 0.22, P<.001),
      and externalization (r = 0.19, P<.001) subscales and total problem (r = 0.15,
      P<.001) scores were positively correlated with time spent watching television.
      Stepwise logistic regression analysis revealed that the only significant
      variables associated with a risk of watching television for more than 2 hours
      were age, gender, social subscale, and attention problem subscale scores of the
      CBCL. CONCLUSION: As evaluated by the CBCL, television viewing time is positively
      associated with social problems, delinquent behavior, aggressive behavior,
      externalization, and total problem scores. Older age, male gender, and decreasing
      social subscale and increasing attention problem subscale scores on the CBCL
      increases the risk of watching television for more than 2 hours.

PMID- 12197800
TI  - Determinants of mother-to-infant human immunodeficiency virus 1 transmission
      before and after the introduction of zidovudine prophylaxis.
AB  - BACKGROUND: Randomized controlled trials have demonstrated that zidovudine
      therapy decreases the mother-to-infant transmission of human immunodeficiency
      virus 1 (HIV-1). Data from large observational studies may provide further
      important findings on the effectiveness at the population level of combined
      treatments in decreasing transmission. OBJECTIVE: To evaluate time trends in
      prophylactic interventions and the determinants of transmission both before and
      after the introduction of antiretroviral prophylaxis, and in treated and
      untreated mother-infant pairs after 1995. DESIGN AND SETTING: Analysis of
      prospective data on 3770 children born to HIV-1-infected women between 1985 and
      1999 and reported to the Italian Register for HIV Infection in Children. MAIN
      OUTCOME MEASURES: Logistic regression random effects models were used to estimate
      crude and adjusted odds ratios for several factors potentially influencing
      vertical transmission for 2 periods-1985 through 1995 (January 1, 1985, through
      December 31, 1995) and 1996 through 1999 (January 1, 1996, through December 31,
      1999), and between treated and untreated children after 1995. RESULTS: The
      transmission rate was 15.5% in the 1985-1995 period and 5.8% in the 1996-1999
      period. By 1999, prophylactic interventions had greatly increased. Antiretroviral
      treatment (ART) usage was 89.9%, (55.1% combination ART) and the elective
      cesarean delivery rate was 81.3%. In multivariate analysis, only elective
      cesarean delivery was associated with a lower risk of mother-to-infant
      transmission before 1995. After 1995, nonbreastfeeding and receipt of ART were
      protective whereas elective cesarean delivery was not significantly protective in
      multivariate analysis. Transmission risk was reduced by 76% with an incomplete
      zidovudine regimen, 88% with a complete regimen, and 93% when the mother received
      combination ART. In the 1996-1999 period, the transmission rate for
      nonbreastfeeding mother-infant pairs was 8.6% with elective cesarean delivery,
      4.4% with any ART, and 2.4% with these interventions combined. CONCLUSION:
      Prophylactic interventions, and in particular ART, reduced perinatal HIV-1
      transmission at a population level in Italy.

PMID- 12197801
TI  - Estimates of the incidence and costs associated with handlebar-related injuries
      in children.
AB  - BACKGROUND: The US Consumer Product Safety Commission is considering handlebar
      regulation regarding impact performance to address the risk of abdominal and
      pelvic organ injuries in bicyclists. OBJECTIVE: To provide national estimates of
      incidence and costs of handlebar-related abdominal and pelvic organ injuries.
      DESIGN AND SETTING: Censuses of hospital discharge data from 19 states were
      extrapolated to determine national estimates. The percentage of abdominal and
      pelvic injuries associated with handlebars was estimated based on a case series
      from a pediatric trauma center. Costs were estimated using standard methods.
      PARTICIPANTS: All subjects younger than 20 years treated as inpatients and
      discharged from acute care hospitals for non-motor vehicle bicycle-related injury
      in 19 states in 1997 and at a pediatric trauma center located in one of the
      states between January 1, 1996, and December 31, 2000. MAIN OUTCOME MEASURES:
      Incidence of bicycle-related handlebar abdominal and pelvic organ injury, total
      hospital charges, lifetime medical payments, lifetime productivity loss, and
      lifetime monetized quality-adjusted life-years. RESULTS: An estimated 1147
      subjects (95% confidence interval, 1082-1215; 1.49 per 100 000 subjects 19 years
      and younger) in the United States had serious non-motor vehicle-involved bicycle
      related abdominal or pelvic organ injury leading to hospitalization in 1997, and
      886 (95% confidence interval, 828-944; 1.15 per 100 000 subjects 19 years and
      younger) of these injuries likely were associated with handlebars. The estimated
      national costs associated with handlebar-related abdominal and pelvic organ
      injuries were $9.6 million in total hospital charges, $10.0 million in lifetime
      medical costs (including claims processing), $11.5 million in lifetime
      productivity losses, and $503.9 million in lifetime monetized quality-adjusted
      life-years. CONCLUSIONS: Handlebar-related abdominal and pelvic organ injuries
      pose a serious health risk to children and result in substantial health care
      costs. Requirements for safer handlebar designs may provide one avenue to achieve
      a health and economic benefit.

PMID- 12197802
TI  - The effectiveness of child-resistant packaging for aspirin.
AB  - OBJECTIVE: To evaluate the effectiveness of child-resistant packaging in reducing
      the mortality rate from the unintentional ingestion of aspirin for children
      younger than 5 years. DESIGN: Estimates of the annual aspirin-related mortality
      rate for children younger than 5 years in the United States were developed for
      the 1958-1990 study period. A multivariate negative binomial regression model was
      then used to estimate the independent effect of the packaging requirements on the
      child mortality rate during the postintervention period. The analysis controlled
      for changes in the per capita use of aspirin, long-term safety trends, and other
      extraneous and potentially confounding factors that may have affected the aspirin
      related child mortality rate. MAIN OUTCOME MEASURE: Estimated percentage
      reduction in the child mortality rate associated with the use of child-resistant
      packaging. RESULTS: After controlling for covariates, the use of child-resistant
      packaging was associated with a 34% reduction in the aspirin-related child
      mortality rate. This mortality rate reduction equates to the prevention of about
      90 child deaths during the 1973-1990 postregulatory study period. CONCLUSIONS:
      Child-resistant packaging has been effective in reducing aspirin-related child
      poisonings. However, because its effectiveness is only partial, further poison
      prevention strategies should be developed and instituted.

PMID- 12197803
TI  - A prospective multicenter study of patient factors associated with hospital
      admission from the emergency department among children with acute asthma.
AB  - BACKGROUND: Recent studies show that objective measures such as peak flow rates
      are strongly associated with asthma admission among adults. OBJECTIVE: To
      identify factors associated with admission among children. METHODS: We performed
      a prospective cohort study as part of the Multicenter Airway Research
      Collaboration. Patients aged 2 to 17 years who presented to the emergency
      department (ED) with acute asthma underwent a structured interview in the ED and
      another by telephone 2 weeks later. The study was performed at 44 EDs in 18 US
      states and 4 Canadian provinces. The decision to admit was made at the discretion
      of the treating physician. Univariate analysis of risk factors for admission was
      followed by multivariate logistic regression. RESULTS: Of the 1178 eligible
      subjects, 275 (23%; 95% confidence interval, 21%-26%) were admitted or placed
      into ED observation units. A multivariate model that included 12 characteristics
      measured at presentation and during the ED stay was associated with an area under
      the receiver operating characteristic curve of 0.91. Demographic factors were not
      independently associated with admission. Severity of symptoms (odds ratio, 1.3)
      and intensity of therapy both before and during ED visit correlated with the
      likelihood of admission. Previous admission for asthma (P =.02) and recent use of
      inhaled corticosteroids (P =.04) also were associated with admission. Peak flows
      were associated with admission but were infrequently (23% overall) measured.
      CONCLUSION: Hospitalization for asthma exacerbation in children is primarily
      associated with clinical indicators in the ED and with historical factors such as
      previous asthma admission or intubation, recent use of corticosteroids, and
      comorbidity.

PMID- 12197804
TI  - Bilateral upper limb weakness and stridor.

PMID- 12197805
TI  - Effectiveness of clinician training in smoking cessation counseling.

PMID- 12197806
TI  - Autonomic seizures and autonomic status epilepticus specific to childhood.

PMID- 12197807
TI  - Peak flow meter use is not where emphasis should be placed.

PMID- 12197809
TI  - Growth hormone therapy in children with idiopathic short stature.

PMID- 12197812
TI  - Children with type 1 diabetes: where are we at?

PMID- 12197813
TI  - Potential pitfalls of healthcare performance indicators.

PMID- 12197814
TI  - Malaria vaccines.

PMID- 12197815
TI  - Hepatitis C-related discrimination in healthcare. Report of the Third
      Australasian Conference on Hepatitis C, Melbourne, March 202.

PMID- 12197816
TI  - Predictors of glycaemic control and hypoglycaemia in children and adolescents
      with type 1 diabetes from NSW and the ACT.
AB  - OBJECTIVES: To audit glycaemic control and incidence of severe hypoglycaemia in
      children and adolescents with type 1 diabetes in New South Wales (NSW) and the
      Australian Capital Territory (ACT). DESIGN: A multicentre, population-based,
      cross-sectional study from 1 September to 31 December, 1999. PARTICIPANTS: 1190
      children and adolescents aged 1.2-15.8 years with type 1 diabetes, identified
      from three hospital-based paediatric diabetes units, four private city-based
      paediatric practices and 18 regional outreach clinics in NSW and the ACT. MAIN
      OUTCOME MEASURES: HbA(1c) level and incidence of severe hypoglycaemia (defined by
      unconsciousness or seizures). RESULTS: The response rate was 67% (1190 of a
      target group of 1765). The median HbA(1c) level was 8.2% (interquartile range,
      7.6%-9.1%). Significant predictors of HbA1c level in a multiple regression model
      were duration (b = 0.05; 95% CI, 0.02-0.07) and insulin dose/kg (b = 0.46; 95%
      CI, 0.27-0.66). At least one episode of severe hypoglycaemia in the previous
      three months was reported in 6.7%, and the rate of severe hypoglycaemia was
      36/100 patient-years. Significant predictors of hypoglycaemia in a Poisson
      regression model were younger age (P = 0.03), male sex (P = 0.04), longer
      diabetes duration (P = 0.02), and > 3 daily insulin injections (P = 0.02), but
      not HbA(1c) level. Children with diabetes had higher BMI standard deviation
      scores compared with population standards, and those in the highest quartile of
      BMI standard deviation score were younger, had shorter diabetes duration and had
      higher HbA(1c) level. CONCLUSIONS: Many children and adolescents with type 1
      diabetes have suboptimal glycaemic control, placing them at high risk of
      developing microvascular complications. Those with longer diabetes duration are
      at increased risk of suboptimal glycaemic control and severe hypoglycaemia and
      should be targeted for interventional strategies.

PMID- 12197817
TI  - Factors associated with severity of hepatic fibrosis in people with chronic
      hepatitis C infection.
AB  - OBJECTIVE: To determine factors associated with hepatic fibrosis development in
      people with chronic hepatitis C virus (HCV) infection. METHODS: As a requirement
      for access to interferon therapy through the S100 scheme in Australia, individual
      pretreatment demographic and clinical information was collected on 2986 patients
      from 61 hospital-based liver clinics from 1 October 1994 through 31 December
      1996. Patients with both a hepatic fibrosis score and an estimated duration of
      HCV infection (910) were divided into 540 with no or minimal hepatic fibrosis
      (stage 0-1) and 370 with moderate to severe hepatic fibrosis (stage 2-3). Seven
      factors were examined: age at HCV infection, sex, ethnicity, source of infection,
      duration of infection, alcohol intake, and mean ALT level. A further analysis was
      performed for all 1135 patients with a hepatic fibrosis score disregarding age at
      and duration of HCV infection. RESULTS: In multivariate analysis, four factors
      were significantly associated with moderate to severe hepatic fibrosis: age at
      infection (OR, 2.33 for age 31-40 years, 5.27 for age > 40 years, and 0.20 for
      age < 15 years, compared with 15-20 years); duration of infection (OR, 1.44 for
      11-20 years, 2.74 for 21-30 years, and 8.71 for > 30 years, compared with < 11
      years); alcohol intake in previous six months (OR, 1.51 for any intake, compared
      with none); and mean ALT level (OR, 1.81 for 2-3 times, 2.27 for > 3 times,
      compared with 1.5-2 times the upper limit of normal). In the analysis
      disregarding age at HCV infection and duration of HCV infection, older age was
      strongly associated with moderate to severe hepatic fibrosis (OR, 2.32 for age 36
      40 years, 2.46 for age 41-50 years, 7.87 for age 51-60 years, and 7.15 for age >
      60 years, compared with 16-30 years). There was no association in either analysis
      with sex or source of HCV infection. CONCLUSION: These factors may assist in
      targeting patients for both liver biopsy-based investigation and therapeutic
      intervention.

PMID- 12197818
TI  - Increase in presentations and procedure rates for hyperparathyroidism in Northern
      Sydney and New South Wales.
AB  - OBJECTIVE: To examine changes in presentation of primary hyperparathyroidism and
      rates of parathyroidectomy in Northern Sydney (the Northern Sydney Area Heath
      Service) and New South Wales (NSW). DESIGN: Retrospective case series January
      1962 - December 2001 and audit of the NSW Department of Health inpatient database
      (1993-1999). SETTING: University of Sydney Endocrine Surgical Unit, Royal North
      Shore Hospital. PARTICIPANTS: 1613 patients undergoing parathyroidectomy during
      the study period. MAIN OUTCOME MEASURES: Age-standardised parathyroidectomy rates
      and indications for surgical intervention. RESULTS: The age-standardised rates of
      parathyroidectomy for primary hyperparathyroidism in women have increased
      significantly in Northern Sydney from 0.14 cases per 100,000 in 1976 to 7.7 cases
      per 100,000 in 1996 (P < 0.001). In NSW there has been an increase in
      parathyroidectomy rates in women from 5.1 cases per 100,000 in 1993 to 12.3 cases
      per 100,000 in 1998 (P < 0.001). Osteoporosis was the most common overall
      indication for surgery in Northern Sydney, accounting for 27% of all cases. The
      proportion of cases presenting with osteoporosis increased significantly from 4%
      in 1962-1980 to 34% over the past decade (P < 0.001). CONCLUSIONS: The rate of
      parathyroidectomy procedures has increased markedly in Northern Sydney and in
      NSW. The investigation of osteoporosis has led to the diagnosis of primary
      hyperparathyroidism in an increasing proportion of cases and has contributed to
      the growing surgical referral rates.

PMID- 12197819
TI  - Quality of care provided by general practitioners using or not using Division
      based diabetes registers.
AB  - OBJECTIVE: To compare the quality of care provided by general practitioners
      participating in diabetes shared-care registers with that provided by GPs not
      using registers. DESIGN: Cross-sectional comparison using Health Insurance
      Commission (HIC) data for patients attending the GPs. PARTICIPANTS AND SETTING:
      155 GPs using diabetes registers, 459 GPs not using registers, and their patients
      with diabetes (as identified by HIC criteria). The study analysed data for the
      period January 1996 to December 1998 and was based on Divisions of General
      Practice within the South Western Sydney Area Health Service. MAIN OUTCOME
      MEASURES: Frequency of visits to GPs and tests ordered within each of six six
      month periods. RESULTS: GPs using the registers had more patients with diabetes,
      and saw those patients more frequently, than GPs not using registers. "Register"
      GPs also ordered tests (for HbA(1c) and microalbuminuria) more frequently than
      "non-register" GPs. CONCLUSION: GPs who participated in diabetes registers were
      more likely to provide patient care that more closely adhered to evidence-based
      guidelines than those who did not. Further research is needed to determine
      whether this was the result of characteristics of the GPs themselves, or their
      practices, or a was a consequence of their participation.

PMID- 12197820
TI  - Surgery dot.com: the quality of information disseminated by Web-based waiting
      time information services.
AB  - OBJECTIVES: To assess Web-based waiting time information services to identify how
      they aimed to meet the information needs of patients and general practitioners,
      and to evaluate how well waiting time information was presented. DESIGN: A cross
      sectional survey of six government websites in English-speaking countries with
      publicly funded hospitals. Sites were evaluated on the clarity of instructions
      about how their information should be used, and the accuracy of the statistics
      they contained was assessed indirectly using methodological criteria. RESULTS:
      The services were judged to encourage GPs and patients to use the statistics to
      avoid surgical units with long waiting times, but overall advice was poor.
      Services did not state whether the statistics predicted expected waiting times,
      and just one stated that the statistics were only intended as a guide. Statistics
      were based on different types of data, and derived at different levels of
      aggregation, raising questions of accuracy. Most sites explained waiting list
      terms, but provided inadequate advice on the uncertainty associated with making
      statistical inferences. CONCLUSIONS: GPs and patients should use Web-based
      waiting time information services cautiously because of a lack of guidance on how
      to appropriately interpret the presented information.

PMID- 12197821
TI  - Determining the sample size in a clinical trial.

PMID- 12197822
TI  - Should we debrief and counsel people who have had psychological shock?

PMID- 12197823
TI  - Cocaine use and cardiovascular complications.
AB  - In Australia, the lifetime use of cocaine is rising, with 3% of the population
      aged over 14 using cocaine in 1991, increasing to 4.5% in 1998, and cocaine use
      accounting for 10% of all deaths secondary to illicit drug use in 1998. Cocaine
      is prepared from the leaves of the plant Erythroxylon coca, and is available as
      cocaine hydrochloride (a water-soluble powder or granule which can be taken
      orally, intravenously or intranasally) and as "freebase" or "crack" cocaine (heat
      stable, melting at high temperatures, thus allowing it to be smoked). Acute
      myocardial infarction (AMI) is the most commonly reported cardiac consequence of
      cocaine misuse, usually occurring in men who are young, fit and healthy and who
      have minimal, if any, risk factors for cardiovascular disease. The mechanism by
      which cocaine induces AMI is largely not understood. Cocaine effect should be
      seriously considered in any young patient with minimal risk factors for cardiac
      disease presenting with AMI, dilated cardiomyopathy, myocarditis or cardiac
      arrhythmias.

PMID- 12197824
TI  - Medical professionalism in the new millennium: a physicians' charter.

PMID- 12197825
TI  - Treatment for hot flushes in women receiving tamoxifen.

PMID- 12197826
TI  - 10: Herpes simplex and varicella-zoster virus infections.
AB  - Any new patient with suspected genital herpes should have diagnostic testing with
      virus identification. Type-specific serological tests that distinguish between
      antibodies for type 1 and type 2 herpes simplex virus (HSV) may be useful to
      determine previous exposure but cannot be used to diagnose recurrences of genital
      herpes. Initial episodes of genital herpes usually require antiviral therapy,
      while recurrences may be treated with continuous antiviral suppression (if
      frequent) or episodic therapy; patient counselling and education (including how
      to recognise lesions) are essential. Topical or systemic therapy is available for
      initial and recurrent non-genital herpes simplex. Primary varicella infection
      (chickenpox) and herpes zoster (shingles) are usually diagnosed clinically, but
      can be confirmed by detection of varicella-zoster virus antigens or nucleic acid
      from swabs of lesions or by antibody tests. Antiviral therapy should be
      considered in chickenpox if disease is complicated or the patient is
      immunocompromised. In herpes zoster, antiviral therapy should be given within 72
      hours of onset to patients aged over 50 years or with severe pain or neurological
      abnormalities to reduce the likelihood and duration of postherpetic neuralgia.
      The availability of effective antiviral therapy makes early diagnosis vital

PMID- 12197827
TI  - Postoperative serious adverse events in a teaching hospital.

PMID- 12197828
TI  - Acute community-acquired meningitis and encephalitis.

PMID- 12197829
TI  - Short-term effectiveness of bupropion for assisting smoking cessation in general
      practice.

PMID- 12197830
TI  - Thalidomide and cancer.

PMID- 12197831
TI  - Surgeons' views about colorectal cancer screening before and after national
      guidelines.

PMID- 12197833
TI  - Low rate of compliance with ergocalciferol therapy in vitamin-D-deficient
      patients with hip fracture.

PMID- 12197834
TI  - Characterization of the human topoisomerase IIbeta (TOP2B) promoter activity:
      essential roles of the nuclear factor-Y (NF-Y)- and specificity protein-1 (Sp1)
      binding sites.
AB  - Eukaryotic topoisomerase II (topo II) catalyses topological genomic changes
      essential for chromosome segregation, chromatin reorganization, DNA replication
      and transcription. Mammalian topo II exists as two isoforms, designated alpha and
      beta. Human topo IIalpha is an important cancer drug target, and an established
      determinant of drug sensitivity and resistance. Human topo IIbeta is also the
      target of anticancer drugs but its role in drug resistance is less clear. The two
      human topo II proteins are encoded by the TOP2A and TOP2B genes, respectively,
      which despite their highly conserved structural organization, are subject to
      distinctly different modes of regulation. In the present study, we have cloned
      and characterized the human TOP2B promoter containing a 1.3 kb fragment of the 5'
      flanking and untranslated region (-1067 to +193). We found that the promoter
      activity of this TOP2B fragment was constant throughout the cell cycle, in
      contrast to the activity of the proximal promoter of TOP2A which was low in
      resting cells and enhanced during proliferation. Analyses of 5'-serially and
      internally deleted luciferase reporter constructs revealed that 80% of the TOP2B
      promoter activity could be attributed to the region between -533 and -481.
      Mutational analyses of putative regulatory elements indicated that two inverted
      CCAAT boxes (ICBs) within this region were essential for TOP2B promoter activity
      and gel mobility-shift assays indicated these sites bound the transcription
      factor nuclear factor-Y (NF-Y). Co-transfection experiments using a dominant
      negative form of subunit A of NF-Y suggested that TOP2B promoter activity
      required direct interaction of NF-Y with the ICBs. In addition, a specificity
      protein-1 (Sp1)-binding GC box located just upstream of the ICBs was shown to
      contribute to TOP2B promoter activity in a synergistic manner with the ICBs. Our
      results suggest that the binding sites for NF-Y and Sp1 are critical for TOP2B
      transcription.

PMID- 12197835
TI  - Dual role for mitogen-activated protein kinase (Erk) in insulin-dependent
      regulation of Fra-1 (fos-related antigen-1) transcription and phosphorylation.
AB  - Insulin regulates the activity of the AP-1 (activator protein-1) transcriptional
      complex in several cell types. One component of the AP-1 complex is the
      transcription factor Fra-1 (fos-related antigen-1), and we have demonstrated
      previously that insulin stimulates the expression of Fra-1 mRNA in CHO.T cells
      [Griffiths, Black, Culbert, Dickens, Shaw, Gillespie and Tavare (1998) Biochem.
      J. 335, 19-26]. Here we demonstrate that insulin stimulates the activity of a fra
      1 promoter linked to a luciferase reporter gene, indicating that the ability of
      insulin to induce expression of Fra-1 mRNA is due, at least in part, to an
      increase in gene transcription. Furthermore, we found that insulin induces the
      serine phosphorylation of Fra-1 and reduces its mobility during SDS/PAGE as a
      result of phosphorylation. The ability of insulin to induce the accumulation of
      Fra-1 mRNA, stimulate the fra-1 promoter and stimulate phosphorylation of Fra-1
      all require the mitogen-activated protein (MAP) kinase cascade, which leads to
      the activation of extracellular-signal-regulated kinase (Erk) 1/2. Consequently,
      our results demonstrate that the Erk cascade plays a dual role in the co
      ordinated regulation of the transcription and the phosphorylation of Fra-1 by
      insulin.

PMID- 12197837
TI  - Review article: biological agents in the treatment of Crohn's disease.
AB  - The main aim of the management of Crohn's disease is to reduce inflammation.
      Current approaches with corticosteroids, immunosuppressive agents, mesalazine and
      antibiotics have limited therapeutic benefit for many patients. Considerable
      progress has been made with regard to our knowledge of the basic mechanisms of
      the disease, which is associated with immunological imbalance characterized by an
      excess of pro-inflammatory cytokines. Recent advances in bio-technology have led
      to the development of many new therapeutic agents, so-called biological agents,
      which selectively target single key processes involved in the pathogenesis of the
      disease. A growing number of biological agents are under investigation in both
      randomized controlled trials and uncontrolled studies. The aim of this review is
      to provide the clinician with an insight into the randomized controlled trials
      published in the literature on the use of biological agents in the treatment of
      Crohn's disease.

PMID- 12197836
TI  - A lysophosphatidic acid analogue is revealed as a potent inhibitor of
      phosphatidylcholine synthesis, inducing apoptosis.
AB  - A previous study demonstrated that cross-desensitization experiments performed
      with the lysophosphatidic acid (LPA) analogues (R)- and (S)-N-palmitoyl
      norleucinol 1-phosphate (PNPAs) inhibited LPA-induced platelet aggregation
      without any stereospecificity. Here we report opposite biological effects of the
      two enantiomers on mitogenesis of IMR-90 fibroblasts in relation to their
      respective metabolism. (R)PNPA was proliferative, while (S)PNPA induced apoptosis
      by specifically inhibiting phosphatidylcholine biosynthesis at the last step of
      the CDP-choline pathway controlled by cholinephosphotransferase. This effect was
      not direct but required dephosphorylation of PNPAs by ecto-lipid phosphate
      phosphatase before cellular uptake of the generated N-palmitoyl-norleucinols
      (PNOHs). Inhibition of cholinephosphotransferase by the derivative (S)PNOH was
      confirmed by an in vitro assay. (S)PNPA proapoptotic effects led us to clarify
      the mechanism linking cholinephosphotransferase inhibition to apoptosis. Three
      proapoptotic responses were observed: the activation of caspase-3, the production
      of ceramides from newly synthesized pools (as demonstrated by the inhibitor
      Fumonisin B1) and finally the activation of stress-activated protein kinase, p38
      and c-Jun N-terminal kinases 1/2, as a result of ceramide increase. Thus our data
      demonstrate that synthetic analogues of LPA might display stereospecific effects
      leading to apoptosis independently of classical LPA-activated pathways.

PMID- 12197838
TI  - Review article: lactose--a potential prebiotic.
AB  - Lactose maldigestion, which affects a large majority of the world's population,
      has been mostly linked with uncomfortable symptoms. In addition, dairy
      consumption is variably blamed or recommended for a number of ill effects. There
      is, however, emerging evidence that certain lactic acid-producing bacteria, which
      selectively consume prebiotics, may be beneficial against some lower intestinal
      diseases. Lactose maldigestion and lactose should perhaps be re-evaluated as a
      potential provider of such a prebiotic. This historical and observational review
      discusses lactose and argues the opinion that it has prebiotic potential.
      Moreover, in maldigesters, natural ingestion or lack thereof may be relevant in
      the pathogenesis of diseases such as colorectal cancer and inflammatory bowel
      diseases.

PMID- 12197839
TI  - The quality of life in patients with Crohn's disease.
AB  - BACKGROUND: Health-related quality of life studies provide insight into the
      influence of Crohn's disease on patients' lives, and the potential impact on
      professional and personal productivity. AIM: To compare health-related quality of
      life in Crohn's disease patients with that in other patients and healthy
      controls, and between medically and surgically treated Crohn's disease patients,
      and to correlate health-related quality of life with Crohn's disease activity.
      METHODS: An expanded MEDLINE search of full length, English language, adult
      Crohn's disease studies from January 1966 to September 2000 was performed. The
      key words utilized were: 'Quality of Life', 'Health Status' or 'Health Related
      Quality of Life' and 'Crohn's' or 'Inflammatory Bowel Disease'. RESULTS: A total
      of 258 articles were identified; 236 subsequently were excluded, leaving 22 for
      analysis. Compared with Crohn's disease patients, the health-related quality of
      life was better in healthy controls and in ulcerative colitis patients (except
      pre-colectomy), but similar to or worse than that in many other medical
      conditions. The health-related quality of life was directly correlated with
      Crohn's disease activity, and was worse in active disease than in remission. The
      health-related quality of life was improved only in the short term in surgically
      vs. medically treated Crohn's disease patients. CONCLUSIONS: Health-related
      quality of life analysis provides important insights into the impact of Crohn's
      disease, and should be included in clinical trials. Researchers, clinicians and
      other health care providers need to be cognizant of the impact of the health
      related quality of life upon patients' lives.

PMID- 12197840
TI  - Meta-analysis: combination therapy with interferon-alpha 2a/2b and ribavirin for
      patients with chronic hepatitis C previously non-responsive to interferon.
AB  - BACKGROUND: The efficacy of interferon-alpha plus ribavirin treatment for
      patients not responding to interferon monotherapy is not well established. AIM:
      To assess the efficacy and safety of combination therapy with interferon-alpha
      2a/2b plus ribavirin by performing a meta-analysis of randomized clinical trials.
      METHODS: A systematic search of electronic databases for randomized clinical
      trials of interferon-alpha 2a/2b plus ribavirin was conducted independently by
      two investigators. Data abstraction was performed. The primary end-point was a
      sustained virological response. Estimates of the common odds ratio were
      calculated using a random effects model. RESULTS: Of the 127 identified studies,
      46 were considered for evaluation and 10 were included (1728 patients). The
      pooled sustained virological response was 12.6% (95% CI, 9.5-16.3%) for
      combination therapy vs. 2% (95% CI, 0.9-4.0%) for interferon monotherapy, with a
      common odds ratio of 5.49. Higher doses of interferon, a longer duration of
      therapy (48 weeks) and genotypes other than 1 and 4 were associated with an
      improvement in response. More side-effects and discontinuations were observed
      with combination therapy than with interferon monotherapy. CONCLUSIONS: Non
      responders to interferon may benefit from re-treatment with combination therapy,
      especially from a 48-week regimen.

PMID- 12197841
TI  - Meta-analysis: ribavirin-induced haemolytic anaemia in patients with chronic
      hepatitis C.
AB  - AIM: To use meta-analysis to study the risk of anaemiarelated to ribavirin
      therapy for chronic hepatitisC. METHODS: The MEDLINE database up to January 2001
      was searched for randomized controlled trials of ribavirin (monotherapy or
      combined with interferon) for chronic hepatitis C. The outcomes evaluated were
      withdrawal from the study due to anaemia, ribavirin dosage reduction due to a
      decrease in haemoglobin and haemoglobin levels below 10 g/dL. RESULTS: Based on
      17 studies, the overall risk difference (ribavirin vs. no ribavirin) for anaemia
      was 0.09 [95% confidence interval (CI), 0.04-0.13]. Two Asian studies reported
      risk differences of 0.29 and 0.22, greater than the pooled risk difference of
      0.07 (95% CI, 0.03-0.12) for 15 non-Asian studies. The risk associated with 1 g
      or more of ribavirin per day was higher (risk difference, 0.09; 95% CI, 0.04
      0.14) than that for 0.8 g of ribavirin per day (risk difference, 0.01; 95% CI, -
      0.04-0.06). CONCLUSIONS: Chronic hepatitis C patients treated with 1 g or more of
      ribavirin per day were at a higher risk of developing anaemia. Reported risks
      were higher among Asian studies, which may be due to differences in study
      entrance criteria, dosage titration strategy or ethnic vulnerability.

PMID- 12197842
TI  - Premature discontinuation of interferon plus ribavirin for adverse effects: a
      multicentre survey in 'real world' patients with chronic hepatitis C.
AB  - BACKGROUND: Interferon-alpha plus ribavirin therapy for chronic hepatitis C is
      associated with adverse effects that lead to therapy discontinuation in up to 27%
      of patients in randomized controlled trials. AIM: To examine the causes and
      predictive factors for therapy discontinuation in patients treated in current
      clinical practice. METHODS: We retrospectively enrolled 441 consecutive patients,
      scheduled to receive interferon-alpha + ribavirin for chronic hepatitis C, in
      five centres. Patients had been treated with 3 or 6 MU interferon-alpha three
      times a week plus ribavirin, 800-1200 mg daily, for 6 or 12 months. RESULTS: One
      hundred and eight [24.5%; confidence interval (CI), 20.5-28.8%] patients failed
      to finish combination therapy because of adverse events. The discontinuation rate
      was higher during the first 6 months of treatment; anaemia was an important cause
      (36.1% of discontinuations); unexplained lipothymia resulted in discontinuation
      in 11 patients. Female gender [hazard ratio (HR) = 1.85; CI, 1.17-2.92], an
      interferon-alpha dose > 15 MU/week (HR = 1.79; CI, 1.12-2.86) and no previous
      interferon-alpha treatment (HR = 1.63; CI, 1.04-2.57) were independent factors
      associated with discontinuation. The simultaneous presence of these factors
      identified patients at high risk for discontinuation [odds ratio (OR) = 10; CI,
      3.98-25.13]. CONCLUSIONS: The study identified some predictive factors for
      adverse event-related discontinuation, which may improve the safety profile and
      effectiveness of interferon-alpha + ribavirin combination therapy in chronic
      hepatitis C.

PMID- 12197843
TI  - A randomized placebo-controlled trial of simethicone and cisapride for the
      treatment of patients with functional dyspepsia.
AB  - AIM: To compare the efficacy of simethicone with placebo and the prokinetic
      cisapride in patients with functional dyspepsia. METHODS: One hundred and eighty
      five patients with functional dyspepsia were randomized and treated in a double
      dummy technique with simethicone (105 mg t.d.s.), cisapride (10 mg t.d.s.) or
      placebo (t.d.s.). The primary outcome measure was the O'Brien global measure of
      the patients' rating of 10 upper gastrointestinal symptoms (graded as absent = 0,
      moderate = 1, severe = 2 or very severe = 3). Outcome measures were assessed at
      baseline and after 2, 4 and 8 weeks of treatment (intention-to-treat). RESULTS:
      At 2, 4 and 8 weeks, treatment with simethicone and cisapride yielded
      significantly (all P values < 0.0001) better improvement of symptoms compared to
      placebo. Simethicone was significantly better than cisapride after 2 weeks (P =
      0.0007), but the differences were not statistically significant after 4 and 8
      weeks. Patients treated with simethicone judged the efficacy of their treatment
      as very good in 46% of cases, compared to 15% and 16% receiving cisapride and
      placebo, respectively. CONCLUSIONS: Simethicone and cisapride were significantly
      better than placebo for symptom control in patients with functional dyspepsia
      after 2, 4 and 8 weeks of treatment. Simethicone was also superior to the
      prokinetic cisapride in the first 2 weeks of treatment.

PMID- 12197844
TI  - Naloxone treatment for irritable bowel syndrome--a randomized controlled trial
      with an oral formulation.
AB  - BACKGROUND: Opioids change gut motility and secretion, causing delayed intestinal
      transit and constipation. Endorphins play a role in the constipation troubling
      some patients with irritable bowel syndrome; hence naloxone, an opioid
      antagonist, may have a therapeutic role. AIM: To assess the efficacy and safety
      of an oral formulation of naloxone in irritable bowel syndrome patients with
      constipation. METHODS: A randomized, double-blind, placebo-controlled trial was
      performed. Patients fulfilling the Rome II criteria for irritable bowel syndrome
      (constipation-predominant and alternating types) were randomized to receive 8
      weeks of treatment with naloxone capsules, 10 mg twice daily, or identical
      placebo. RESULTS: Twenty-eight patients entered the study, which was completed by
      25. 'Adequate symptomatic relief' was recorded in six of 14 on naloxone and three
      of 11 on placebo. Whilst the differences were not significant, improvements in
      severity gradings and mean symptom scores for pain, bloating, straining and
      urgency to defecate were greater with naloxone than placebo for all parameters.
      In addition, quality of life assessments improved to a greater extent in patients
      taking naloxone. CONCLUSIONS: Preliminary results suggest that naloxone is well
      tolerated and beneficial in patients with irritable bowel syndrome and
      constipation. A larger clinical trial is needed to provide sufficient statistical
      power to assess efficacy.

PMID- 12197845
TI  - The effect of baclofen on gastro-oesophageal reflux, lower oesophageal sphincter
      function and reflux symptoms in patients with reflux disease.
AB  - BACKGROUND: Baclofen decreases gastro-oesophageal reflux episodes in healthy
      subjects by reducing the incidence of transient lower oesophageal sphincter
      relaxations. AIM: To investigate the effect of baclofen on reflux symptoms,
      oesophageal pH and lower oesophageal sphincter manometry in patients with gastro
      oesophageal reflux disease. METHODS: A double-blind, placebo-controlled, two-way
      crossover design was used to study the effect of baclofen on heartburn and
      regurgitation 3 h after a provocation test meal in 37 patients with gastro
      oesophageal reflux disease. Additionally, in 20 of these patients, the effect of
      baclofen on oesophageal pH, transient lower oesophageal sphincter relaxations and
      basal lower oesophageal sphincter pressure was studied. RESULTS: Baclofen
      significantly decreased the acid reflux time and the incidence of gastro
      oesophageal reflux episodes (8.3 +/- 8.8% vs. 12.4 +/- 12.0%, P = 0.03 and 10.9
      +/- 7.3 per 3 h vs. 18.7 +/- 12.4 per 3 h). The incidence of transient lower
      oesophageal sphincter relaxations was significantly lower with baclofen than with
      placebo (15.1 +/- 6.4 per 3 h vs. 22.8 +/- 5.4 per 3 h, P < 0.0001). Lower
      oesophageal sphincter pressure and the percentage of transient lower oesophageal
      sphincter relaxations associated with reflux were not affected by baclofen. No
      significant effect on symptom scores was observed. CONCLUSIONS: Baclofen
      decreases post-prandial acid reflux in patients with gastro-oesophageal reflux
      disease by reducing the incidence of transient lower oesophageal sphincter
      relaxations. No effect of a single dose of baclofen on reflux symptoms could be
      demonstrated in this 3-h post-prandial study.

PMID- 12197846
TI  - Dynamics of Helicobacter pylori infection in early childhood in a high-risk group
      living in Germany: loss of infection higher than acquisition.
AB  - BACKGROUND: The dynamics of Helicobacter pylori infection in early childhood are
      not yet well understood. AIM: To conduct a prospective study in a population of
      children known to be at high risk of H. pylori infection to elucidate the
      incidence and loss of infection in childhood. METHODS: Asymptomatic Turkish
      children [aged 1 (n = 56 children), 2 (n = 55 children) and 4 years (n = 69
      children)] at baseline, on whom participating paediatricians had performed
      routine health screening examinations between September 1997 and October 1998,
      were included in the study. A follow-up was performed about 1 year later. The
      infection status was defined by means of an antigen-based stool assay. RESULTS:
      In total, for 137 of 180 (76%) children, follow-up information was available. At
      baseline examination, the prevalence of infection in children with follow-up
      information was 27%[95% confidence interval (CI), 20-35%]. The incidence of H.
      pylori infection among previously uninfected children was 7% (95% CI, 3-14%) and
      the loss of infection among previously infected children was 35% (95% CI, 20-54%)
      during follow-up. CONCLUSIONS: This prospective cohort study in a high-risk group
      of children living in Germany showed that H. pylori colonization may often not
      persist at an early age. Furthermore, the use of penicillins and macrolides may
      be associated with the loss of infection at an early age.

PMID- 12197848
TI  - Foetal intrauterine growth restrictions with Helicobacter pylori infection.
AB  - BACKGROUND: Helicobacter pylori infection has been associated with growth
      restriction in young children. AIM: To determine whether there is an association
      between H. pylori infection and intrauterine growth restriction. METHODS: Four
      hundred and forty-eight consecutive pregnant women (aged 15-44 years), attending
      for routine examinations in the third trimester, were enrolled. Clinical,
      demographic and previous obstetric data, as well as smoking history, were
      collected. At delivery, the weight, height, gender and status of the neonate were
      recorded; intrauterine growth restriction was defined if the birth weight was
      below the 10th percentile according to the gestational age for infants born in
      Australia. RESULTS: Eighty-nine (20%) women were seropositive for H. pylori. The
      prevalence of H. pylori was significantly lower in Caucasians (17%) vs. non
      Caucasians (42%, P < 0.0001). There were 34 (7.5%) cases of intrauterine growth
      restriction (7% Caucasians, 16% Asians, 12% Aborigines and 0% Pacific Islanders).
      Intrauterine growth restriction was more common in H. pylori-seropositive women
      than in H. pylori-seronegative women [13.5% vs. 6%; odds ratio (OR) = 2.41; 95%
      confidence interval (CI), 1.14-5.08; P = 0.018]. A multiple logistic regression
      model revealed that smoking (OR = 3.55; 95% CI, 1.62-7.79; P = 0.002), maternal
      height (OR = 0.48; 95% CI, 0.28-0.80; P = 0.005) and H. pylori seropositivity (OR
      = 2.59; 95% CI, 1.12-5.95; P = 0.025) were all independent risk factors for
      intrauterine growth restriction. CONCLUSIONS: H. pylori infection in pregnant
      women may affect foetal intrauterine growth.

PMID- 12197847
TI  - Impact of supplement with Lactobacillus- and Bifidobacterium-containing yogurt on
      triple therapy for Helicobacter pylori eradication.
AB  - AIM: To test whether supplements of Lactobacillus- and Bifidobacterium-containing
      yogurt (AB-Yogurt) affect the success of Helicobacter pylori eradication.
      METHODS: One hundred and sixty H. pylori-infected patients were randomized into a
      triple-plus-yogurt group or a triple-only group, receiving 1 week of triple
      therapy with and without supplements of AB-Yogurt, respectively. In the triple
      plus-yogurt group, AB-Yogurt was continued for 4 weeks after triple therapy.
      Eight weeks later, patients were assessed for the success of H. pylori
      eradication. The stool samples of 22 randomly selected patients, 11 from each
      group, were provided on enrolment, at the first week and at the fifth week for
      evaluation of the percentage of Bifidobacterium in anaerobes. RESULTS: By
      intention-to-treat analysis, the triple-plus-yogurt group had a higher H. pylori
      eradication rate than the triple-only group (91% vs. 78%, P < 0.05). The per
      protocol H. pylori eradication rates were similar for both groups (93.5% vs. 89%,
      P = N.S.). Only patients supplemented with AB-Yogurt showed restoration of the
      percentage of Bifidobacterium in the anaerobes of stools at the fifth week to the
      level in the stools on enrolment. CONCLUSIONS: Supplement with AB-Yogurt can
      improve the intention-to-treat eradication rates of H. pylori, and can restore
      the depletion of Bifidobacterium in stools after triple therapy.

PMID- 12197849
TI  - Effects of enteric-coated, low-dose aspirin on parameters of platelet function.
AB  - BACKGROUND: Aspirin is widely used as an anti-thrombotic drug; however, it has
      been suggested that enteric-coated formulations of aspirin may be less
      bioavailable and less effective as anti-thrombotic agents. AIM: To assess the
      effect of a formulation of enteric-coated, low-dose (81 mg) aspirin on serum
      generated thromboxane B2 and platelet aggregation in healthy subjects. METHODS:
      Twenty-four subjects participated in a double-blind, randomized, placebo
      controlled, parallel-group, multiple-dose study. Twelve subjects in each of two
      groups received a daily oral dose of enteric-coated aspirin (81 mg) or matching
      placebo for 7 days. Serum thromboxane B2 and platelet aggregation (using 1 mm
      arachidonic acid and 1 microg/mL collagen as agonists) were measured 1-3 days
      prior to day 1, on day 1 (prior to therapy) and 4 h after the last dose on day 7.
      RESULTS: After seven daily doses of enteric-coated aspirin, the mean percentage
      inhibition from baseline of ex vivo generated serum thromboxane B2 was 97.4%,
      compared with a 7.8% increase after placebo treatment. The mean percentage
      inhibition of arachidonic acid- and collagen-induced platelet aggregation was
      97.9% and 70.9%, respectively, following enteric-coated aspirin, compared with -
      1.0% and 2.7%, respectively, after placebo. CONCLUSIONS: The anti-platelet
      effects of multiple, daily, low-dose aspirin (as assessed by inhibition of serum
      thromboxane B2 and platelet aggregation) are not adversely affected by enteric
      coating.

PMID- 12197850
TI  - Depression in Parkinson's disease.

PMID- 12197851
TI  - SSRIs vs. TCAs in the treatment of panic disorder: a meta-analysis.
AB  - OBJECTIVE: To compare the short-term efficacy of selective serotonin reuptake
      inhibitors (SSRIs) vs. tricyclic antidepressants (TCAs) in the treatment of panic
      disorder (PD) a meta-analysis was conducted. METHOD: Included were 43 studies (34
      randomized, nine open), pertaining to 53 treatment conditions, 2367 patients at
      pretest and 1804 at post-test. Outcome was measured with the proportion of
      patients becoming panic-free, and with pre/post Cohen's d effect sizes,
      calculated for four clinical variables: panic, agoraphobia, depression, and
      general anxiety. RESULTS: There were no differences between SSRIs and TCAs on any
      of the effect sizes, indicating that both groups of antidepressants are equally
      effective in reducing panic symptoms, agoraphobic avoidance, depressive
      symptomatology and general anxiety. Also the percentage of patients free of panic
      attacks at post-test did not differ. The number of drop-outs, however, was
      significantly lower in the group of patients treated with SSRIs (18%) vs. TCAs
      (31%). CONCLUSION: SSRIs and TCAs are equal in efficacy in the treatment of panic
      disorder, but SSRIs are tolerated better.

PMID- 12197852
TI  - Differential effectiveness of newer and older antidepressants appears mediated by
      an age effect on the phenotypic expression of depression.
AB  - OBJECTIVE: A possible mechanism whereby the serotonin reuptake inhibitor (SSRI)
      antidepressants may not (overall) be as effective as the tricyclic (TCA)
      antidepressants is explored. METHOD: Clinical psychiatrists rated the
      effectiveness of past antidepressant medications in a clinical panel study of
      patients with a major depressive disorder, with 200 having previously received a
      TCA and 219 an SSRI. RESULTS: Analyses indicated decreased SSRI effectiveness
      with age in those with the melancholic subtype. TCA effectiveness appeared
      uninfluenced by age and depressive subtype. CONCLUSION: Findings suggest why the
      broader-based TCAs may be more effective than the SSRIs in implicating age and
      depressive subtype influences.

PMID- 12197853
TI  - Relationship between perfectionism, personality disorders and agoraphobia in
      patients with panic disorder.
AB  - OBJECTIVE: In earlier reports, we found that perfectionism might be involved in
      the development and/or maintenance of agoraphobia in panic disorder. The present
      report extends this work by examining the relationship between perfectionism and
      comorbidity with personality disorders in panic disorder patients with
      agoraphobia (PDA) and those without agoraphobia (PD). METHOD: We examined
      comorbidity of personality disorders by Structured Clinical Interview for DSM-III
      R Personality Disorders (SCID-II) and assessed perfectionism using
      multidimensional perfectionism scale in 56 PDA and 42 PD patients. RESULTS: The
      PDA group met criteria for at least one personality disorder significantly more
      often than the PD group. With stepwise regression analyses, avoidant and
      obsessive-compulsive personality disorders emerged as significant indicators of
      perfectionism in patients with panic disorder. CONCLUSION: These findings suggest
      that perfectionism in panic disorder patients may be more common in those with
      comorbid personality disorders, and may be an important target for preventive and
      therapeutic efforts.

PMID- 12197854
TI  - Personality features of patients with mixed and pure manic episodes.
AB  - OBJECTIVE: To test the hypothesis that patients with a mixed manic episode show
      different personality features than patients with a pure manic episode. METHOD:
      Sixteen patients with a mixed manic episode (broad criteria) and 26 patients with
      a pure manic episode were assessed with diagnostic interviews (SCID I/II) as well
      as instruments for depression, mania and personality. RESULTS: Even after
      controlling for age as well as depression and mania score at assessment, no
      differences between the two groups emerged concerning either personality features
      as assessed with the NEO-five-factor inventory (NEO-FFI) or personality
      disorders. CONCLUSION: We found no difference between patients with mixed mania
      and patients with pure mania concerning their personality features. Possible
      reasons for this are being discussed.

PMID- 12197855
TI  - Childhood maltreatment and personality disorders in adult patients with binge
      eating disorder.
AB  - OBJECTIVE: To examine the association between retrospective reports of different
      types of childhood maltreatment and current personality disorders (PDs) in
      patients with binge eating disorder (BED). METHOD: A total of 116 consecutive out
      patients with DSM-IV BED were assessed with diagnostic interviews and completed
      the Childhood Trauma Questionnaire to assess childhood maltreatment in five
      domains (emotional abuse, physical abuse, sexual abuse, emotional neglect and
      physical neglect). RESULTS: Eighty-two percent of patients reported some form of
      childhood maltreatment and 30% met criteria for at least one PD. Emotional abuse
      was significantly associated with cluster C PD overall and specifically with
      avoidant PD. CONCLUSION: Reports of emotional abuse - but not other forms of
      maltreatment - were associated with greater likelihood of a PDs in patients with
      BED.

PMID- 12197856
TI  - Temperament, character, and personality disorders: etiologic, diagnostic,
      treatment issues.
AB  - OBJECTIVE: In this paper, we explore the underlying dimensional structure of
      personality disorder, propose a novel approach to its diagnosis, and outline our
      concepts of its etiology and treatment based on the seven factor psychobiological
      model of temperament and character. METHOD: Temperament and character traits were
      evaluated in a consecutive series of 109 psychiatric out-patients, with or
      without personality disorder and varying mood and anxiety states. RESULTS: Low
      scores on character dimensions consistently correlated with high symptom counts
      for personality disorder. Each subtype of personality disorder created a unique
      combination of correlations with the four temperament traits. CONCLUSION:
      Temperament and Character Inventory (TCI) temperament and character traits
      efficiently diagnose personality disorder and differentiate its individual
      subtypes. Character traits are used to diagnose the presence and the severity of
      personality disorder, whereas temperament traits are used for differential
      diagnosis. The distinction between temperament and character provides an
      attractive theoretical basis for etiological postulates and treatment of
      personality disorder.

PMID- 12197857
TI  - Markers for depression in Parkinson's disease.
AB  - OBJECTIVE: To assess whether general risk factors for depression are also markers
      of depression in patients with Parkinson's disease (PD) and to identify
      additional disease-specific markers. METHOD: A two-step logistic regression was
      performed on data from 161 consecutively referred PD patients, 40 of whom
      suffered from major depressive disorder. A first logistic model was created with
      five general risk factors for depression. Next, five potential disease-specific
      markers were added to see whether this would improve the model. RESULTS: The
      logistic model of general risk factors for depression also predicted depression
      in PD patients. A family history of depression was the most important marker.
      'Right-sided onset' was the only disease-specific marker that improved the model.
      CONCLUSION: Established risk factors for depression in the general population are
      also markers of depression in PD. The importance of correcting for general risk
      factors for depression in the search for disease-specific risk factors is
      stressed.

PMID- 12197858
TI  - Major depressive disorder in Parkinson's disease: a register-based study.
AB  - OBJECTIVE: To investigate whether patients with Parkinson's disease (PD) were at
      an increased risk of developing major depression compared with patients having
      other medical illnesses with a comparable degree of disability. METHOD: Case
      register linkage study of Danish Psychiatric Central Register (DPCR)and Danish
      National Hospital Register (DNHR). Three study cohorts were identified: all
      patients with PD, osteoarthritis, and diabetes. The rate of discharge diagnosis
      of depression on re-admission was estimated using competing risks models in
      survival analyses. The rates for patients with PD were compared with those of
      patients with osteoarthritis, and diabetes. RESULTS: The study sample identified
      211 245 patients in the hospital registers with one of the index diagnoses. An
      increased incidence of developing depression was found for women and men
      throughout their lifetime when this incidence was compared with the control
      groups. CONCLUSION: The findings support the hypothesis that depression in
      patients with PD is a consequence of brain dysfunction.

PMID- 12197859
TI  - Obstetrical complications and the development of postpartum depressive symptoms:
      a prospective survey of the MATQUID cohort.
AB  - OBJECTIVE: To prospectively investigate in a cohort of pregnant women the
      association between obstetrical complications (OCs) and depressive symptomatology
      in the early postpartum period. METHOD: A total of 441 pregnant women attending
      the State Maternity Hospital in Bordeaux were interviewed during the third
      trimester of pregnancy, then at 3 days and 6 weeks after birth. Maternal
      depression was assessed using the Edinburgh Postnatal Depression Scale (EPDS).
      Data on a large range of pregnancy, delivery and neonatal somatic adverse events
      were collected by interviewing the mothers. Data on OCs were rated using the
      McNeil-Sjostrom scale for OCs. A dimensional definition of postnatal depression
      (EPDS summary score 6 weeks after delivery) was used to explore the relationships
      between OCs and early postnatal depressive symptoms. RESULTS: Exposure to severe
      OCs during pregnancy was associated with more intense depressive symptoms in the
      early postnatal period, independently from demographic characteristics, marital
      adjustment, parity, and a history of depressive or anxiety disorder during
      pregnancy (adjusted B=0.16, 95% CI 0.007, 0.30, P=0.04). No association was found
      between the severity of postnatal depressive symptoms and labour/delivery or
      neonatal complications. CONCLUSION: Severe pregnancy complications may increase
      the severity of postnatal depressive symptoms by acting as acute or chronic
      stressors during pregnancy. The links between OCs, maternal psychopathology, and
      child development, need to be explored further.

PMID- 12197860
TI  - Magnetic motor threshold and response to TMS in major depressive disorder.
AB  - OBJECTIVE: The aim of this study was to examine motor threshold (MT) during
      treatment with transcranial magnetic stimulation (TMS). METHOD: The TMS was
      administered to 46 patients with depression and 13 controls. TMS was performed at
      90% power of measured MT. The stimulation frequency was 10 Hz for 6 s, for 20
      trains, with 30 s inter-train intervals. The trial included 20 sessions. Patients
      and controls were assessed on various outcome measures. RESULTS: The MT values
      were comparable between patients and controls. Neither demographic nor clinical
      variables were factors in determining MT. MT was not shown to have any predictive
      value regarding outcome of treatment. CONCLUSION: In this study, MT at baseline
      or changes in MT during the treatment period were not able to discriminate
      between patients and controls and were not found to have any predictive value
      with regard to treatment outcome.

PMID- 12197861
TI  - Relative increase in choline in the occipital cortex in chronic fatigue syndrome.
AB  - OBJECTIVE: To test the hypothesis that chronic fatigue syndrome (CFS) is
      associated with altered cerebral metabolites in the frontal and occipital
      cortices. METHOD: Cerebral proton magnetic resonance spectroscopy (1H MRS) was
      carried out in eight CFS patients and eight age- and sex-matched healthy control
      subjects. Spectra were obtained from 20 x 20 x 20 mm3 voxels in the dominant
      motor and occipital cortices using a point-resolved spectroscopy pulse sequence.
      RESULTS: The mean ratio of choline (Cho) to creatine (Cr) in the occipital cortex
      in CFS (0.97) was significantly higher than in the controls (0.76; P=0.008). No
      other metabolite ratios were significantly different between the two groups in
      either the frontal or occipital cortex. In addition, there was a loss of the
      normal spatial variation of Cho in CFS. CONCLUSION: Our results suggest that
      there may be an abnormality of phospholipid metabolism in the brain in CFS.

PMID- 12197862
TI  - Out-patient behaviour therapy in alcoholism: treatment outcome after 2 years.
AB  - OBJECTIVE: The main aim of the study was the evaluation of out-patient
      behavioural approaches in alcohol dependence. Additionally, the persistence of
      treatment effects and the impact of psychiatric comorbidity in long-term follow
      up was examined. METHOD: A total of 120 patients were randomly assigned to non
      specific supportive therapy or to two different behavioural therapy programmes
      (coping skills training and cognitive therapy) each comprising 26 weekly
      sessions; the follow-up period lasted 2 years. RESULTS: Patients undergoing
      behavioural therapy showed a consistent trend towards higher abstinence rates;
      significant differences between the two behavioural strategies could not be
      established. Moreover, the results indicate a reduced ability of cognitive
      impaired patients to cope with short-time abstinence violations and at a reduced
      benefit from behavioural techniques for patients with severe personality
      disorders. CONCLUSION: Behavioural treatment yielded long-lasting effects and met
      high acceptance; yet, still in need of improvement is the development of specific
      programmes for high-risk patients.

PMID- 12197863
TI  - Motivational interviewing among psychiatric in-patients with substance use
      disorders.
AB  - OBJECTIVE: There were three aims of the present study: 1) to document patterns of
      substance misuse among psychiatric in-patients with comorbid alcohol and other
      drug (AOD) use; 2) to examine associations among psychiatric and substance use
      diagnoses and readiness to change; and 3) to evaluate the effectiveness of an
      opportunistic motivational interview on engagement in a Specialist Substance
      Misuse Service (SSMS). METHOD: One hundred and sixty subjects were randomly
      assigned to receive either a motivational interview or no intervention. RESULTS:
      Overall, 66.3% of subjects met intervention threshold for cannabis, 60.6% for
      alcohol and 22.5% for amphetamines. There was a bimodal distribution of stage of
      change for cannabis use which was associated with age, with precontemplation
      being associated with older age and less frequent use. Attendance at the SSMS was
      low and unrelated to intervention status. CONCLUSION: A different approach to
      treatment is recommended, including early intervention among cannabis users.

PMID- 12197864
TI  - The effect of alcohol consumption on cost of care in severe psychotic illness: a
      report from the UK700 study.
AB  - OBJECTIVE: Alcohol misuse in psychotic patients is common and leads to poor
      treatment outcome. This study examines the relationship between alcohol
      consumption and cost of care in patients with a severe psychotic illness. METHOD:
      Patient care was evaluated over 2 years for 708 patients. Patient reported
      alcohol consumption was evaluated at initial interview. The outcome measure was
      cost of care over 2 years. RESULTS: There was no difference in mean cost of care
      between non-drinkers, moderate and heavy drinkers. Increased alcohol consumption
      (measured as a continuous variable, adjusted for baseline characteristics) was
      associated with lower cost of care. CONCLUSION: Heavier alcohol consumers did not
      incur more treatment costs and may, indeed, cost less than other patients. This
      may reflect higher levels of drinking being associated with better overall
      functioning, poorer engagement with services or exclusion from services.

PMID- 12197866
TI  - Bioterrorism: how serious is the threat?

PMID- 12197867
TI  - Biological warfare in a historical perspective.
AB  - There are some early examples of biological warfare (BW), but in modern times it
      was used first for sabotage by Germany during WWI. Development of biological
      weapons on a military significant scale was initiated in several countries in the
      period between the world wars. During WWII, several countries had active programs
      such as the USA, UK, Canada, Germany, Japan and the Soviet Union. It was only
      Japan that on a fairly large scale used BW. The US program continued until 1969,
      when President Nixon took a decision to end it in connection with signing the
      BTWC. The Soviet Union had also continued its program after the war, and this was
      enhanced after signing the BTWC: in the 1980s the program consisted of around
      fifty facilities and involved around 60,000 people. The Soviet Union produced and
      maintained a large stockpile of BW-agents. After the collapse of the Soviet
      Union, and due to pressure from USA and UK, President Yeltsin issued a decree in
      1992 banning continued offensive BW activity. However, there are still concerns
      of residual activity in Russia. Another program of concern is the Iraqi BW
      program. After 10 years of UN inspections that were stopped in 1998, there are
      still many unanswered questions concerning the BW program. There was also a
      covert BW-program in South Africa that was terminated around 1993. There have
      also been a number of allegations of alleged use or possession. In addition,
      there are indications that 10-12 states are now trying to acquire BW, and this
      assessment is based on intelligence information, mainly from the USA. For example
      Iraq, North Korea, Iran, Syria, Sudan and Libya. Another aspect is the strong
      driving force of technology developments to promote this type of program, opening
      new risks for future potential military misuse.

PMID- 12197868
TI  - Laboratory diagnosis and biosafety issues of biological warfare agents.
AB  - Bioterrorism events have been rare until recently. Many clinical laboratories may
      not be familiar with handling specimens from a possible bioterrorism attack.
      Therefore, they should be aware of their own responsibilities and limitations in
      the handling and treatment of such specimens, and what to do if they are
      requested to process clinical samples. The Centers for Disease Control and
      Prevention has developed the Laboratory Response Network to provide an organized
      response system for the detection and diagnosis of biological warfare agents
      based on laboratory testing abilities and facilities. There are potentially many
      biological warfare agents, but probably a limited number of agents would be
      encountered in case of an attack, and their identification and laboratory safety
      will be discussed.

PMID- 12197869
TI  - Bacillus anthracis and antibacterial agents.
AB  - Anthrax is one of the oldest threats to humankind, and remains endemic in animals
      in many parts of the world. Human cases are infrequent, and some result from
      biological warfare. This review summarizes the current knowledge on the
      antibacterial activity of available antibiotics. For potential use in the most
      severe cases of anthrax, antibacterials need to exhibit potent in vitro activity,
      intracellular bioactivity, and suitable locations in lymph nodes. In animal
      models, it has been shown that doxycycline and fluoroquinolones are the most
      active compounds. There is a lack of data for animal models for macrolides and
      ketolides, some of them exhibiting good in vitro activity. However, systemic
      anthrax (inhalation or gastrointestinal) is mainly due to anthrax toxin, and
      therapy directed against intoxication is needed as basic treatment.

PMID- 12197870
TI  - Anthrax in Europe: its epidemiology, clinical characteristics, and role in
      bioterrorism.
AB  - In the 2001 bioterrorist attack in the United States, in which at least 22 cases
      of anthrax occurred, there was initial uncertainty as to whether the index case
      was acquired from natural sources, and many of the additional cases posed
      diagnostic challenges to clinicians unfamiliar with the disease. The existence in
      Europe of terrorist groups with demonstrated violent tendencies suggests Europe
      is not immune to bioterrorist attack, and the same epidemiological and clinical
      confusion could happen here. Bacillus anthracis is distributed widely in the
      soils of Europe and foci of animal disease occur, notably in southern and eastern
      Europe. Sporadic human cases occur in these areas, and occasional additional
      cases have been acquired from contaminated, imported materials or acquired in
      countries outside of Europe, where anthrax may be common. Depending upon the
      intent of a bioterrorist, illness-caused B. anthracis could take one of several
      clinical forms-inhalational, cutaneous or gastrointestinal-and each would pose
      diagnostic difficulties. Understanding the epidemiologic, pathophysiologic and
      bioterrorism principles of anthrax are the clinician's best means of early
      detection of cases.

PMID- 12197871
TI  - Anthrax, tularemia, plague, ebola or smallpox as agents of bioterrorism:
      recognition in the emergency room.
AB  - Bioterrorism has become a potential diagnostic consideration in infectious
      diseases. This article reviews the clinical presentation and differential
      diagnosis of potential bioterrorist agents when first presenting to the hospital
      in the emergency room setting. The characteristic clinical features of inhalation
      anthrax, tularemic pneumonia, plague pneumonia, including laboratory and
      radiographic finding, are discussed. Ebola vieus and smallpox are also discussed
      as potential bioterrorist-transmitted infections from the clinical and
      epidemiologic standpoint. In addition to the clinical features of the infectious
      diseases mentioned, the article discusses the infectious disease control and
      epidemiologic implications of these agents when employed as bioterrorist agents.
      The review concludes with suggestions for postexposure prophylaxis and therapy.

PMID- 12197872
TI  - Smallpox--eradicated, but a growing terror threat.
AB  - Smallpox is a disease that followed humanity for thousands of years up until 30
      years ago. It was possible to eradicate, because an effective live vaccine from
      crossreacting vaccinia could be developed. Twenty years have passed since
      vaccinations stopped and very few people are protected against the disease today.
      Variola today has become an object of discussion due to the possibility that it
      can be used as a bioweapon. Due to the number of complications that can be
      expected a general vaccination is probably not possible. Research is ongoing to
      develop new vaccines. Many countries are improving their capabilities to respond
      to a renewed threat of a smallpox epidemic.

PMID- 12197873
TI  - A procedure for differentiating between the intentional release of biological
      warfare agents and natural outbreaks of disease: its use in analyzing the
      tularemia outbreak in Kosovo in 1999 and 2000.
AB  - The events of 11 September and the subsequent anthrax outbreaks in the USA have
      opened the world's eyes to the threat posed by terrorist groups, criminal
      organizations and lone operators who will stop at nothing to achieve their goals.
      The open or covert use of pathogens and toxins as biological warfare agents can
      no longer be ruled out. Against this background, the appearance of an unusual
      disease must be studied in order to clarify whether it is a natural or
      artificially caused occurrence. This issue was recently raised in discussions
      with local representatives and relief organizations during a tularemia epidemic
      in Kosovo from October 1999 to May 2000. This paper will present a procedure
      which attempts to use certain criteria to identify or rule out the use of
      biological warfare agents in the event of an unusual outbreak of disease. Data
      and findings gathered by routine epidemiologic and microbiological studies often
      provide only an indirect answer to this problem. For this reason, various
      criteria were formulated and points allocated to represent their importance,
      allowing us to deduce in a semiquantitative manner the degree of possibility of
      an artificial genesis of outbreaks. The significance and characterization of each
      criterion are discussed. An analysis of the tularemia epidemic in Kosovo based on
      the procedure described here indicates that a deliberate release of the causative
      agent of tularemia, Francisella tularensis, as a biological warfare agent is
      doubtful. In this paper, an approach is described to discriminate between the
      intentional use of biological warfare agents and natural outbreaks of infectious
      diseases. The developed model is flexible and considers the political, military
      and social analysis of the crisis-afflicted region, the specific features of the
      pathogen, and the epidemiologic and clinical characteristics of the epidemic.

PMID- 12197874
TI  - Biological weapons and bioterrorism preparedness: importance of public-health
      awareness and international cooperation.
AB  - Biological weapons and biological terrorism have recently come into focus due to
      the deliberate release of Bacillus anthracis via mail delivered in the USA. Since
      the 1930s, biological weapons have been developed in a number of countries. In
      1975, the Biological and Toxin Weapons Convention entered into force; this
      prohibits the use of these weapons and has been signed by a large majority of
      countries (144). Unfortunately, several countries failed to respect this treaty.
      The Soviet Union continued and expanded its biological weapons program, and after
      the Gulf War it was revealed that Iraq also had an extensive biological weapons
      program. Large-scale deliberate release of, Bacillus anthracis, for example, or
      an epidemic following a release of smallpox virus, would have a devastating
      effect. This has motivated the world community to strengthen the Biological and
      Toxin Weapons Convention with a control mechanism which has, as yet, not been
      successful. Sweden, like other countries, is enhancing its preparedness with
      regard to stocks of antibiotics and vaccines, related to these improving the
      diagnostics these and similar agents, and is setting up an epidemiologic task
      force that can be used in infectious disease emergencies such as the deliberate
      release of biological warfare agents. International cooperation in this area has
      to be enhanced, not least in the European Union.

PMID- 12197875
TI  - Challenges associated with creating a pharmaceutical stockpile to respond to a
      terrorist event.
AB  - The Centers for Disease Control and Prevention (CDC) was called into action to
      develop a National Pharmaceutical Stockpile (NPS). The NPS was created to respond
      to terrorism events involving blast, chemical and biological agents. There are
      many challenges associated with creating, managing and using such an asset. This
      paper provides a helpful background for clinicians and those planning to develop
      pharmaceutical and/or medical materiel stockpiles for national use. It also
      describes major challenges and offers suggestions for meeting those challenges.

PMID- 12197876
TI  - Problems associated with potential massive use of antimicrobial agents as
      prophylaxis or therapy of a bioterrorist attack.
AB  - In addition to the direct sanitary damage of a terrorist attack caused by
      biological weapons, the consequences of the massive stockpiling and consumption
      of antimicrobial agents in order to treat or prevent the disease under a
      potential epidemic due to pathogenic bacteria must also be considered. Bacillus
      anthracis, Francisella tularensis and Yersinia pestis are the bacteria most
      likely to be used as terrorist weapons. Tetracyclines, quinolones and
      aminoglycoside are the antibiotics of choice against these microorganisms. The
      recent terrorist attack with anthrax spores in the USA caused a substantial
      increase in the sales of ciprofloxacin, as thousands of citizens received
      antibiotic prophylaxis for either confirmed or suspected exposure to anthrax, and
      many others stockpiled antibiotic supplies at their homes under a panic scenario.
      The massive consumption of antimicrobial drugs may lead to the selection of
      antibiotic resistant strains, and to the appearance of undesirable side effects,
      such as anaphylaxis or teratogenesis. National health authorities must develop
      realistic protocols in order to detect, treat and prevent mass casualties caused
      by biological weapons. An antibiotic stockpile has to be planned and implemented,
      and home stockpiling of antibiotics must be strongly discouraged.

PMID- 12197877
TI  - High-dose intravenous immunoglobulin (hdIVIg) in the treatment of autoimmune
      blistering disorders.

PMID- 12197878
TI  - The strength of the OVA-induced airway inflammation in rats is strain dependent.
AB  - To examine the influence of genetics on the OVA-induced allergic inflammatory
      response in lungs we compared rats that are genetically Th2-predisposed (Brown
      Norway, inbred) or not genetically predisposed (Sprague Dawley, outbred). Rats
      were sensitized with ovalbumin (OVA) and challenged four weeks later with OVA
      aerosol. Eighteen hours after challenge, lung tissue was studied for evaluation
      of numbers of eosinophils, neutrophils, macrophages and mast cells, as well as
      for expression of P-selectin, E-selectin, intercellular adhesion molecule-1 (ICAM
      1) and vascular cell adhesion molecule-1 (VCAM-1) on endothelial cells. From a
      separate portion of the pulmonary tissue, leucocytes were isolated to analyse
      numbers of IFNgamma and IL-4 producing cells (ELISPOT assay) and frequencies of T
      cell subsets and B cells. We found increased numbers of eosinophils and
      neutrophils in the lung, an increased number of IL-4 producing cells in lung cell
      isolates and increased levels of serum (OVA- specific)-IgE in both rat strains.
      In addition, expression of E-selectin and ICAM-1 was up regulated in both rat
      strains whereas expression of VCAM-1 was only up regulated in the BN rat.
      Although the 'allergic' Th2 response to OVA was detectable in both rat strains,
      it was more pronounced in the BN rat than in the SD rat. However, the SD rat,
      which is not predisposed to respond in either a Th2 or Th1-like way, appeared
      capable of mounting an allergic response to OVA. This suggests that other factors
      than genetic contribute to allergic disease.

PMID- 12197879
TI  - Simultaneous activation of natural killer T cells and autoantibody production in
      mice injected with denatured syngeneic liver tissue.
AB  - Denatured syngeneic liver tissue prepared by mechanical procedures was
      intraperitoneally injected into adult C57BL/6 mice. In parallel with a decrease
      in the total number of lymphocytes in the liver, spleen, and thymus from days 1-7
      after the injection, the proportion of the CD4+NK1.1+CD3(int) subset of these
      cells (i.e. natural killer T or NKT cells) increased in the liver. Even the
      absolute number of these NKT cells increased in the liver on days 14 and 21. In
      response to the injection of denatured liver tissue, tissue damage was induced in
      the liver, as shown by elevated levels of serum transaminases and hepatocyte
      degeneration observed by electron microscopy. Sera obtained on days 7 and 14
      contained autoantibodies including anti-DNA antibodies. The proportion of
      CD1d(high)B cells in the liver was found to decrease on days 1-7. In other words,
      denatured liver tissue stimulated both NKT cells and certain B cells in the
      liver. These results suggest that liver lymphocytes might contain not only
      autoreactive T cells (e.g. CD3(int) or NKT cells) but also some B cells (e.g. B-1
      cells) which produce autoantibodies and that the denatured tissue had the
      potential to stimulate these lymphocytes and to evoke an autoimmune-like state.

PMID- 12197880
TI  - The Th2-response in mercuric chloride-induced autoimmunity requires continuing
      costimulation via CD28.
AB  - Mercuric chloride (HgCl2)-induced autoimmunity in Brown Norway (BN) rats is a
      highly polarized polyclonal Th2-driven autoimmune response with increased IgE
      production, lymphoproliferation, vasculitis and proteinuria. The increase in
      serum IgE concentration is clearly measurable by day 4 after the first HgCl2
      injection and peaks between days 15 and 20. Treatment with CD80 and CD86
      antibodies prior to administration of HgCl2 completely suppresses the autoimmune
      process. To determine whether interruption of CD28 signalling after initial
      stimulation of the Th2-response would be suppressive, antibody treatment was
      delayed. BN rats were given 5 doses of HgCl2 subcutaneously on alternate days.
      CD80 and CD86 antibodies, or an isotype control, were given daily for 3 days and
      then on alternate days until day 12 commencing either on the day of the first
      HgCl2 injection (day 0) or on days 4 or 8. Treatment from day 0 reduced serum IgE
      concentrations to below baseline (median 9.34 microg/ml on day 0 versus 4.6
      microg/ml, on day 5, P = 0.03) suggesting that ongoing costimulation via CD28 is
      required to maintain basal serum IgE production. Delaying treatment until day 4
      or day 8 after the first HgCl2 injection resulted in significant inhibition of
      IgE secretion, lymphoproliferation, and vasculitis, although less markedly than
      when treatment was commenced on day 0. These data indicate that CD28-mediated
      costimulation is not only required for the initiation of the Th2-response but is
      required for maintenance of a maximal response, making this an attractive
      therapeutic target for antibody-mediated autoimmune diseases.

PMID- 12197881
TI  - Temporary restoration of immune response against Toxoplasma gondii in HIV
      infected individuals after HAART, as studied in the hu-PBMC-SCID mouse model.
AB  - We studied immune reconstitution against the parasite T. gondii in HIV-infected
      patients treated for 1 years with highly active antiretroviral therapy (HAART).
      We used SCID mice, humanized with peripheral blood mononuclear cells (PBMC) from
      patients, which were then infected with T. gondii cysts. Mice humanized with PBMC
      from patients before the start of HAART were highly susceptible to infection. In
      contrast, mice humanized with PBMC from patients who had received HAART for 6
      months displayed higher survival rates, correlating with lower intracerebral
      parasite loads. However, this resistance was lost during follow up because mice
      humanized with PBMC from patients treated with HAART for 12 months survived for
      no longer than mice that had not been humanized. Specific lymphocyte
      proliferation assays showed that the increase in proliferative response depended
      on treatment duration and that HAART induced changes in IFN-gamma secretion in
      the presence of Toxoplasma antigens. Thus, our results indicate partial immune
      reconstitution against T. gondii in HIV-infected patients following HAART,
      possibly due to changes in the patterns of specific IFN-gamma production and
      redistribution of functional memory CD4+ cells.

PMID- 12197882
TI  - Inhibition of human natural killer cell activity by cereulide, an emetic toxin
      from Bacillus cereus.
AB  - The lipophilic toxin, cereulide, emitted by emetic food poisoning causing strains
      of Bacillus cereus, is a powerful mitochondria toxin. It is highly lipophilic and
      rapidly absorbed from the gut into the bloodstream. We tested how this toxin
      influences natural killer (NK) cells, which are important effectors in defence
      against infections and malignancy. Cereulide inhibited cytotoxicity and cytokine
      production of natural killer cells, caused swelling of natural killer cell
      mitochondria, and eventually induced natural killer cell apoptosis. The
      suppressive effect on cytotoxicity was fast and toxic concentration low, 20-30
      microg/l. As the emesis causing concentration of cereulide is around 10 microg/kg
      of total body mass, our results suggest that emesis causing or even lower doses
      of cereulide may also have a systemic natural killer cell suppressive effect.

PMID- 12197883
TI  - Novel promiscuous HLA-DQ HIV Nef peptide that induces IFN-gamma-producing memory
      CD4+ T cells.
AB  - We describe the highly conserved sequence 56-68 of the HIV Nef protein as the
      first promiscuous HLA-DQ HIV-derived peptide. The Nef peptide exhibits an albeit
      rare capacity to bind 6 different HLA-DQ molecules whereas no binding is observed
      with the 10 HLA-DR molecules tested. In agreement with these data, after
      immunization with the Nef peptide, HLA-DQ transgenic Abeta degrees mice display a
      vigorous cellular and humoral response while the specific immune response of HLA
      DR expressing mice is minimal. The promiscuous potentiality of the Nef 56-68
      peptide in humans has been confirmed by ex vivo immunization experiments with
      CD4+ T cells from 14 healthy donors expressing different HLA genotypes. Nef 56-68
      specific CD4+ T cells rapidly acquire a memory cell phenotype and are
      characterized by the preferential usage of the TCR Vbeta 6.1 gene segment and
      predominant production of IFN-gamma. Taken together, these data indicate that the
      Nef 56-68 peptide constitutes an attractive component of vaccines aiming at
      inducing or enhancing HIV-specific T cell immunity.

PMID- 12197884
TI  - Respiratory syncytial virus induces prostaglandin E2, IL-10 and IL-11 generation
      in antigen presenting cells.
AB  - Bronchiolitis caused by respiratory syncytial virus (RSV) infection is a major
      cause of hospitalization in children under 1 years of age. The disease
      characteristically does not induce protective immunity. However, a mononuclear
      peribronchiolar and perivascular infiltrate during RSV infection is suggestive of
      an immune-mediated pathogenesis. Macrophages and dendritic cells (DCs) play an
      essential role in the initiation and maintenance of immune response to pathogens.
      To analyse interactions of RSV and immune cells, human cord blood derived
      macrophages and dendritic cells were infected with RSV. Both cells were found to
      be infected with RSV resulting in the activation of macrophages and maturation of
      dendritic cells as reflected by enhanced expression of several surface antigens.
      In the next set of experiments, generation of mediators was compared between
      cells infected with RSV, parainfluenza (PIV3) and influenza virus as well as
      ultracentrifuged virus free supernatant. Whereas the supernatant did not induce
      release of mediators, all three live virus infections induced IL-6 production
      from macrophages and DC. Influenza virus infection induced predominantly IL-12
      p75 generation in DC. In contrast, RSV induced strong IL-11 and prostaglandin E2
      release from both macrophages and DCs. In addition, RSV but not influenza and
      parainfluenza virus induced a strong IL-10 generation particularly from
      macrophages. Since IL-10, IL-11 and PGE2 are known to act immunosuppressive
      rather than proinflammatory, these mediators might be responsible for the delayed
      protective RSV specific immune response.

PMID- 12197885
TI  - IL-10 enhances B-cell IgE synthesis by promoting differentiation into plasma
      cells, a process that is inhibited by CD27/CD70 interaction.
AB  - Interleukin-10 (IL-10) is a major regulatory cytokine of inflammatory responses
      that is considered to play an important role in specific immunotherapy. However,
      whether IL-10 enhances or inhibits B-cell IgE production has remained a matter of
      contention. To clarify the effect of IL-10 on IgE synthesis in the presence of IL
      4 and CD40 signalling, we examined B-cell proliferation, germline epsilon
      transcripts and plasma cell differentiation. In addition, the effect of CD27
      signalling on IgE synthesis in the presence of IL-10, IL-4 and CD40 signalling
      was investigated. IL-10 facilitated the production of IgE in mononuclear cells
      and highly purified B-cells, enhanced B-cell proliferation and, most importantly,
      promoted the generation of plasma cells. However, IL-10 did not enhance
      expression of germline epsilon transcripts. The addition of CD27 signalling
      through the use of CD32-CD27 ligand (CD70) double transfectants significantly
      diminished the B-cell proliferation, IgE synthesis and plasma cell
      differentiation enhanced by IL-10. IL-10 enhances B-cell IgE production by
      promoting differentiation into plasma cells. CD27/CD70 interactions under IL-10
      and sufficient CD40 cosignalling exert the opposite effect on IgE synthesis. The
      results of this study indicate that precautions are critical when planning
      immunotherapy using IL-10 in IgE-related allergic diseases.

PMID- 12197886
TI  - Generation of a recombinant Fab antibody reactive with the Alzheimer's disease
      related Abeta peptide.
AB  - A recombinant Fab antibody, designated 1E8-4b, which reacts with the Alzheimer's
      disease (AD)-related Abeta peptides, Abeta[1-40], Abeta[1-42] and Abeta[1-43] has
      been developed. The 1E8-4b Fab was constructed by cloning the V(H)C(H1) and
      V(L)C(L) domains from the parent hybridoma 1E8 antibody, reported previously to
      recognize these Abeta peptides. Briefly, a C-terminal Flag tag sequence was
      incorporated into this construct, which was ligated into the vector pHFA2 and
      expressed in Escherichia coli. Following purification on an M2 anti-Flag affinity
      column, the 1E8-4b recombinant Fab antibody was shown to bind plaques within
      sections of brain tissue from CERAD-defined AD patients by immunohistochemistry.
      ELISA, epitope mapping and immunoblotting confirmed the recognition of the Abeta1
      40/42/43] peptides by the 1E8-4b Fab. The 1E8-4b Fab did not recognize APP695 or
      APP770 which contain the Abeta sequence. The Abeta specificity of the recombinant
      1E8-4b Fab antibody was identical to the parent 1E8 monoclonal antibody.

PMID- 12197887
TI  - Immunosuppressive properties of human amniotic membrane for mixed lymphocyte
      reaction.
AB  - The combination of allograft limbal transplantation (ALT) and amniotic membrane
      transplantation (AMT) has been applied in the treatment of severe ocular surface
      diseases. The beneficial effect of this combination has been thought to result
      from possible immunosuppressive ability of amniotic membrane (AM). However, the
      mechanisms of any such ability remain unknown. In this study, we investigated
      whether human AM has the ability to suppress allo-reactive T cell responses in
      vitro. For mixed lymphocyte reaction (MLR), lymphocytes isolated from lymph nodes
      of C57BL/6 mice (Mls1b, Vbeta6+) were cultured with irradiated splenocytes from
      DBA/2 mice (Mls1a, Vbeta6-) with or without human AM. For carboxyfluorescein
      diacetate succinimidyl ester (CFSE) experiments, responder lymph node cells were
      labelled with a stable intracellular fluorescent dye and cultured with irradiated
      stimulator cells. The ratio of responder Vbeta6+ T cells was then determined by
      FACS analysis, and the division profiles of responder Vbeta6+ T cells were
      analysed by CFSE content. Furthermore, Th1 and Th2 cytokine synthesis by allo
      reactive T cells in MLR culture supernatants was determined by enzyme-linked
      immunosorbent assay (ELISA). Addition of AM to the MLR culture resulted in the
      significant inhibition of thymidine incorporation compared with control culture
      lacking AM. The population of responder CD4+Vbeta6+ T cells was significantly
      reduced in the AM-treated culture in comparison to control. CFSE analysis
      revealed less division and lower proliferation of responder CD4+Vbeta6+ T cells
      in cultures with AM than without. In addition, allo-rective T cell synthesis of
      both Th1 (IL-2 and IFNgamma) and Th2 (IL-6 and IL-10) type cytokine was
      significantly decreased in the presence of AM. These results indicate that human
      AM has the ability to suppress allo-reactive T cells in vitro. This inhibitory
      effect likely contributes to the success of the ALT-AMT combination.

PMID- 12197888
TI  - T-cell reactivity to glutamic acid decarboxylase in stiff-man syndrome and
      cerebellar ataxia associated with polyendocrine autoimmunity.
AB  - Antibodies to glutamic acid decarboxilase (GAD-Abs) are present in the serum of
      60-80% of newly diagnosed type 1 diabetes (DM1) patients and patients with
      autoimmune polyendocrine syndrome (APS) associated with DM1. Higher titre of GAD
      Abs are also present in the serum of 60% of patients with stiff-man syndrome
      (SMS) and all reported patients with cerebellar ataxia associated with
      polyendocrine autoimmunity (CAPA). Several studies suggest that GAD-Abs may play
      a critical role in the pathogenesis of SMS and CAPA but little is known about T
      cell responsiveness to GAD-65 in these neurological diseases. To analyse cell
      mediated responses to GAD, we studied the peripheral blood lymphocyte
      proliferation and cytokine responses to recombinant human GAD-65 in 5 patients
      with SMS, 6 with CAPA, 9 with DM1, 8 with APS and 15 control subjects. GAD-65
      specific cellular proliferation was significantly higher in SMS than in CAPA,
      DM1, APS or controls. In contrast, only T cells from CAPA patients showed a
      significantly high production of interferon-gamma after GAD stimulation, compared
      to all other patients and controls. No differences were found for IL-4
      production. These results suggest that, despite similar humoral autoreactivity,
      cellular responses to GAD are different between SMS and CAPA, with a greater
      inflammatory response in CAPA, and this difference may be relevant to the
      pathogenesis of these diseases.

PMID- 12197889
TI  - Role of reactive oxygen species in neutrophil apoptosis following ingestion of
      heat-killed Staphylococcus aureus.
AB  - Neutrophils, short-lived leucocytes that die by apoptosis, play an important role
      in the first stage of defense against bacterial infections. It has been reported
      that phagocytosis of intact bacteria or Candida albicans can accelerate
      neutrophil apoptosis. However, the mechanism of phagocytosis-mediated neutrophil
      apoptosis is not well characterized. In this study, we evaluated whether
      ingestion of heat-killed Staphylococcus aureus (S. aureus) enhances neutrophil
      apoptosis and whether this type of apoptosis is mediated by oxidative stress by
      using antioxidants and polymorphonuclear leucocytes (PMNs) from patients with
      chronic granulomatous disease (CGD). Co-culture of PMNs with varying doses of S.
      aureus resulted in accelerated PMN death in a dose- and time-dependent manner.
      Increased PMN apoptosis was observed by both Annexin V and PI staining. Similar
      results were observed in PMNs of CGD patients. Dimethyl sulphoxide (DMSO, an OH*
      scavenger) did not significantly inhibit either S. aureus-ingested PMN apoptosis
      or spontaneous PMN apoptosis. On the other hand glutathione (GSH, an H2O2
      scavenger) significantly inhibited both types of apoptosis. Our findings suggest
      that oxygen-independent pathways may mainly operate in the process of
      phagocytosis-induced apoptosis.

PMID- 12197890
TI  - Long-term serological evaluation of patients with cystic echinococcosis treated
      with benzimidazole carbamates.
AB  - Seeking better immunological markers indicating the long-term outcome of cystic
      echinococcosis (CE) after chemotherapy we studied 23 patients receiving
      albendazole, clinically followed for 8 years, and grouped ultrasonographically
      according to therapeutic outcome. Antibody responses against a partially purified
      fraction of hydatid fluid (HFF) and antigen B (AgB) were evaluated by indirect
      haemagglutination (IHA), ELISA and immunoblotting (IB). Although IHA titres
      varied over the course of treatment, differences in mean antibody titres to HFF
      between groups were significant only at 4 years (P = 0.031). IgG isotype
      expression remained unchanged during follow-up whereas IgE expression decreased
      in patients with cured or stable disease. AgB disclosed higher IgG4 expression (P
      < 10(-4); P = 0.025) and lower IgG1 expression than HFF (P < 10(-4); P = 0.022).
      IHA antibody titres were higher in patients with progressive than in those with
      cured or stable disease, even in those with the same cyst type. ELISA isotype
      profiles differed between groups, particularly for type CE 3, 4 and 5 cysts:
      higher serum IgG1 and IgG3, lower IgG4 and IgE in patients with cured or stable
      disease. Although combined serological testing provides scarce information on the
      long-term outcome of CE after chemotherapy it may be useful for reviewing in a
      retrospective study the outcome of a cyst and for assessing the host-parasite
      relationship.

PMID- 12197891
TI  - Allo-immunization elicits CCR5 antibodies, SDF-1 chemokines, and CD8-suppressor
      factors that inhibit transmission of R5 and X4 HIV-1 in women.
AB  - Studies in humans suggest that allo-immunization induces CC-chemokines, CD8
      suppressor factors (SF) and anti-HIV immunity. Here we report that allo
      immunization with unmatched leucocytes from partners of women with recurrent
      spontaneous abortion elicits specific antibodies to the CCR5 receptor. Such
      antibodies inhibit replication of M-tropic HIV-1 (R5) and MIP-1beta-mediated
      chemotaxis. These CCR5 antibodies were also found in the sera of multiparous
      women that were naturally immunized by semi-allogeneic fetal antigens. The
      specificity of these antibodies was demonstrated by adsorption with CCR5
      transfected HEK-293 cells, a baculovirus CCR5 preparation and a peptide of the
      2nd extra-cellular loop of CCR5. Allo-immunization also stimulated increased
      concentrations of the CXC chemokine, SDF-1alpha and CD8-SF that inhibit T-tropic
      HIV-1 (X4) replication. We suggest that allo- immunization may elicit (a) CC
      chemokines, CCR5 antibodies and CD8-SF that inhibit M-tropic HIV-1 infection and
      (b) the CXC chemokine SDF-1alpha and CD8-SF that inhibit T-tropic HIV-1
      infection.

PMID- 12197892
TI  - Atypical X-linked SCID phenotype associated with growth hormone
      hyporesponsiveness.
AB  - Severe combined immunodeficiency (SCID) is a heterogeneous group of disorders
      characterized by defect of T- and B-cell immunity. In many cases of autosomal
      recessive SCID, thus far described, the molecular alteration involves genes
      encoding for molecules that participate in the signal transduction. We report on
      a patient affected by a combined immunodeficiency, characterized by severe T-cell
      functional impairment, in spite of a close to normal number of circulating mature
      type T and B cells. NK cells were absent. Associated with the immunodeficiency,
      this patient also showed short stature characterized by very low growth velocity,
      delayed bone age and absence of increase of the plasma levels of Insulin growth
      factor-I (IGF-I) after growth hormone (GH) in vivo stimulation indicating
      peripheral hyporesponsiveness to GH. Evaluation of the protein tyrosine
      phosphorylation events occurring following either T-cell receptor (TCR) or GH
      receptor (GHR) triggering revealed striking abnormalities. No molecular
      alteration of GHR gene was found, thus suggesting the presence of postreceptorial
      blockage. Mutational screening and expression analysis failed to reveal any
      molecular alteration of JAK2 and STAT 5 A/B genes thus ruling out the involvement
      of these genes in the pathogenesis of this form of SCID. Mutational analysis of
      IL2Rgamma chain gene revealed the presence of a L183S missense mutation, thus
      indicating an atypical and a more complex clinical presentation of this X-linked
      form of SCID. At our knowledge, this is the first report on the GH
      hyporesponsiveness in this disease.

PMID- 12197894
TI  - Systemic treatment with anti-CD40 antibody stimulates Langerhans cell migration
      from the skin.
AB  - Epidermal Langerhans cells (LCs) play a pivotal role in the initiation of
      cutaneous immune responses. The maturation of LCs and their migration from the
      skin to the T cell areas of draining lymph nodes are essential for the delivery
      and presentation of antigen to naive T cells. CD40, which acts as a costimulatory
      molecule, is present on LCs and the basal layer of keratinocytes in the skin. We
      show here that systemic treatment of mice with anti-CD40 antibody stimulates the
      migration of LCs out of the epidermis with a 70% reduction in LC numbers after 7
      days, although changes in LC morphology are detectable as early as day 3. LC
      numbers in the epidermis returned to 90% of normal by day 21. As well as
      morphological changes, LC showed up-regulated levels of Class II and ICAM-1, with
      only minimal changes in CD86 expression 3 days following anti-CD40 treatment.
      Despite increased levels of Class II and ICAM-1, epidermal LC isolated from anti
      CD40 treated mice were poor stimulators of a unidirectional allogeneic mixed
      leucocyte reaction (MLR), as were epidermal LC isolated from control mice. These
      results indicate that CD40 stimulation is an effective signal for LC migration,
      distinct from maturation of immunostimulatory function in the epidermis, which is
      not altered. These observations may have important implications for the mechanism
      of action of agonistic anti-CD40 antibodies, which have been used as an adjuvant
      in models of infection and experimental tumours and the primary immunodeficiency
      Hyper IgM syndrome caused by deficiency of CD40 ligand.

PMID- 12197893
TI  - T-cells in the cerebrospinal fluid express a similar repertoire of inflammatory
      chemokine receptors in the absence or presence of CNS inflammation: implications
      for CNS trafficking.
AB  - It is believed that chemokines and their receptors are involved in trafficking of
      T-cells to the central nervous system (CNS). The aim of the current study was to
      define the expression on cerebrospinal fluid (CSF) T-cells of six chemokine
      receptors associated with trafficking to sites of inflammation. Flow cytometry
      was used to detect chemokine receptor expression. We observed that CD3+T-cells in
      the CSF express a restricted array of inflammatory chemokine receptors,
      specifically CXCR3, CCR5 and CCR6, but little CCR1-3. This repertoire was
      independent of the presence of CNS inflammation, since comparable findings were
      obtained in patients with multiple sclerosis (MS) and individuals with non
      inflammatory neurological diseases. The enrichment of CCR5+T-cells in the CSF
      could largely be explained by higher frequency of CD4+/CD45RO+T-cells in this
      compartment. In contrast, CD4+/CD45RO+T-cells expressing CXCR3 were significantly
      enriched in CSF as compared with blood. Similar levels of CCR6+/CD3+T-cells were
      observed in blood and CSF, while levels of CCR2+/CD3+T-cells were lower in CSF
      than in blood. The CSF was virtually devoid of CCR5+/CXCR3- T-cells, suggesting
      that the expression of CCR5 alone is not sufficient for the trafficking of CD3+T
      cells to the CSF. We hypothesize that CXCR3 is the principal inflammatory
      chemokine receptor involved in intrathecal accumulation of T-cells in MS. Through
      interactions with its ligands, CXCR3 is proposed to mediate retention of T-cells
      in the inflamed CNS.

PMID- 12197895
TI  - Autoantibodies in vitiligo patients are not directed to the melanocyte
      differentiation antigen MelanA/MART1.
AB  - Recent studies have demonstrated the presence of circulating MelanA (MART1)
      specific cytotoxic T lymphocytes in a significant number of vitiligo patients
      when compared to control subjects. High levels of the skin-homing receptor
      cutaneous lymphocyte-associated antigen were expressed on the T cells and their
      frequency correlated with the extent of depigmentation and disease activity in
      the vitiligo patients. The present study was designed to examine vitiligo patient
      sera for the presence of autoantibodies to MelanA. The incidence of
      autoantibodies to MelanA in patients with vitiligo (n = 51) and in healthy
      individuals (n = 20) was examined using a radiobinding assay with 35S]-labelled
      MelanA and using Western blot analysis with a glutathione S-transferase (GST)
      MelanA fusion protein. Autoantibodies to MelanA could not be detected in any of
      the vitiligo patient sera or control sera analysed using either of these
      detection systems. It is therefore possible that MelanA only induces cellular
      rather than humoral autoreactivity in vitiligo.

PMID- 12197896
TI  - Treatment of oral pemphigoid with intravenous immunoglobulin as monotherapy. Long
      term follow-up: influence of treatment on antibody titres to human alpha6
      integrin.
AB  - SUMMARY: Oral pemphigoid (OP) is a chronic autoimmune disease, involving the oral
      cavity, characterized by a homogenous linear deposition of immunoglobulins,
      complement, or both along the basement membrane zone (BMZ) and a subepithelial
      blister formation. The alpha6/beta4 heterodimer is an integrin family of adhesion
      receptors, which mediates basal cell to matrix interactions. Recent evidence
      suggests a pathophysiologic role for antibodies against human alpha6 integrin in
      blister formation in OP, in organ culture studies. Fifty percent of OP patients
      have been reported to experience disease progression to involve other mucosal
      tissues, including the eye and larynx. To prevent this extension of disease,
      systemic therapy with systemic corticosteroids, dapsone, and immunosuppressive
      agents has been recommended. The use of intravenous immunoglobulin (IVIg) in the
      treatment of pemphigoid has been recently described. In this study, we present
      the use of IVIg, in a group of seven patients, with severe OP, in whom systemic
      conventional treatment was contraindicated. To determine the influence of
      treatment on antibodies to human alpha6 integrin in OP, seven patients with OP
      treated with IVIg therapy and a comparable control group of seven patients with
      OP, treated with conventional therapy, were evaluated at monthly intervals, for a
      12 consecutive month treatment period. An effective clinical response was
      observed in all seven patients treated with IVIg therapy, after a mean treatment
      period of 4.5 months. IVIg therapy induced a prolonged and sustained clinical
      remission in all seven patients after a mean treatment period of 26.9 months. A
      statistically significant difference was observed in the quality of life pre- and
      post-IVIg therapy (P < 0.001). Both the study and the control groups had a very
      similar initial serological response to treatment. A statistically significant
      reduction in the antibody titres was observed after four months of treatment, in
      both groups (P = 0.015). Thereafter, patients treated with IVIg therapy had a
      faster rate of decline in the antibody titres, and the difference in the rate of
      decline between the study and control groups became statistically significant
      after six months of treatment (P = 0.03). The use of IVIg therapy resulted in
      reduction of antialpha6 antibody titres and in inducing and maintaining both a
      sustained, clinical and serological remission.

PMID- 12197897
TI  - Activation of pulmonary T cells in corticosteroid-resistant and -sensitive
      interstitial pneumonitis in dermatomyositis/polymyositis.
AB  - To study the activation states and cytokine profiles of pulmonary T cells in
      corticosteroid-resistant and corticosteroid-sensitive interstitial pneumonitis
      (IP) in dermatomyositis (DM)/polymyositis (PM), we examined the activation
      markers and cytokine profiles of T cells in bronchoalveolar lavage fluids (BALF)
      from patients with IP in DM/PM before prednisolone therapy and then compared the
      activation states of T cells according to the therapeutic response of IP to
      prednisolone therapy. CD25+ CD4+ T cells in BALF were significantly increased in
      both corticosteroid-resistant and corticosteroid-sensitive IP in DM/PM as
      compared with those in controls without IP. Furthermore, CD25+ CD4+ T cells in
      BALF were significantly more increased in corticosteroid-resistant IP than those
      in cortico teroid- sensitive IP. Moreover, CD25+ CD8+ T cells in BALF were
      significantly increased only in corticosteroid-resistant IP, but not in
      corticosteroid-sensitive IP or controls without IP. IFN-gamma mRNA was detected
      in BALF T cells in corticosteroid-resistant and corticosteroid-sensitive IP but
      not in controls without IP, whereas IL-4 mRNA was virtually undetected in BALF T
      cells in both the IP groups. However, there were no significant differences in
      CD4/CD8 ratio of BALF T cells, HLA-DR+ BALF T cells or CD25+ and HLA-DR+
      peripheral blood T cells between the two IP groups. These results indicate that
      activated Th1-type pulmonary T cells play an important role in the development of
      corticosteroid- resistant IP in DM/PM and that the increase in CD25+ CD8+ T cells
      in BALF is a useful indicator for corticosteroid-resistant IP in DM/PM and hence
      may be an indicator for early use of cyclosporin.

PMID- 12197898
TI  - In vivo activated T cells in rheumatoid synovitis. Analysis of Th1- and Th2-type
      cytokine production at clonal level in different stages of disease.
AB  - T-cell cytokines play a crucial role in the pathogenesis and progression of
      rheumatoid arthritis (RA). Their detection in the joint, however, is impaired by
      the complex network present in the synovium. Although many synovial T cells show
      signs of previous activation, only a few express interleukin (IL)-2 receptor,
      marker of recent activation. The aim of this study was to analyse the cytokine
      production by in vivo activated (IL-2R +) T cells from RA at different stages of
      the disease. For this purpose, T cells were isolated from peripheral blood and
      synovial fluid of four patients with active RA, two at the onset of the disease,
      one in the early phase during treatment, one in long-lasting chronic phase. One
      patient was studied at the onset of the disease and 52 months later. Cells were
      initially expanded with a low dose of IL-2, cloned and analysed for cytokine
      production. The results showed a strong predominance of T helper (Th) 1 clones in
      the blood and a slight prevalence of Th0 clones in the joint of all the four
      patients. Interferon-gamma and IL-2 production was higher in the long-lasting RA,
      whereas IL-4 synthesis was prevalent in early RA. Enrichment in IL-10-producing
      clones was present only in the joint of the untreated patients. The longitudinal
      study confirmed the differences in cytokine production between early and late
      phases of disease. These data confirm that RA is mainly a Th1-driven condition.
      However, in vivo activated synovial T cells produce also Th2-type anti
      inflammatory cytokines, such as IL-4 and IL-10. The synthesis of both cytokines
      is a feature of the very early phase of RA, although the selective recruitment of
      IL-10-producing T cells is quickly lost.

PMID- 12197899
TI  - Intramolecular epitope spreading among anti-caspase-8 autoantibodies in patients
      with silicosis, systemic sclerosis and systemic lupus erythematosus, as well as
      in healthy individuals.
AB  - Dysregulation of apoptosis through the Fas-Fas ligand pathway is relevant in
      autoimmune disease onset. We recently reported elevated serum levels of sFas in
      patients with silicosis, systemic sclerosis (SSC) and systemic lupus
      erythematosus (SLE), and proposed a block of apoptosis in the pathogenesis. The
      disturbance of apoptosis in lymphocytes including autoreactive clones could
      induce autoantibody production. Since autoantibodies directed against unknown
      antigens are present in the sera of these patients, the sera samples were
      examined for the presence of autoantibodies directed to caspase-8. Using Western
      blotting, autoantibodies against caspase-8 were detected in healthy individuals
      and in over 60% of patients. Using epitope mapping employing 12 amino acid
      polypeptides with SPOTs system, a minimum of 4 epitopes and a maximum of 13 were
      found, which implied that epitope spreading was in progress. It is noteworthy
      that two important catalytic cystein residues were included within the epitopes;
      firstly the active site cystein Cys287, and secondly Cys360 located in the unique
      pentapeptide motif QACQG. Using recombinant human caspase-8 linked protein chip
      array, autoantibodies were identified and molecular weight determined. The
      antibodies were mainly IgG; 80% were subclass IgG1(lambda); 20% were IgG4(kappa).
      Despite the ratio of human light chain kappa:lambda = 2:1, the predominance of
      IgG1(lambda) is noticeable. Anti-caspase-8 autoantibodies are detectable in
      healthy individuals and in patients suffering silicosis, SSc or SLE. A few
      epitopes were detected in healthy individuals compared to those suffering
      autoimmune diseases, indicating the intramolecular epitope spreading.
      Relationship of autoantibodies and the clinical background of the patients
      requires clarification.

PMID- 12197903
TI  - Genomics of Helicobacter pylori.
AB  - During this review period, we have definitely entered into the genomic era. The
      Helicobacter pylori studies reported here illustrate the use of most of the
      technologies currently available to globally interrogate the genome of a
      pathogen. Global analysis of the gene content of H. pylori strains gives insight
      into the extent of its genetic diversity and its in vivo evolution. Our
      understanding of the particularities of H. pylori as a gastric pathogen
      colonizing a unique niche has been improved by studies aimed at: (i) the
      identification of H. pylori-specific genes; (ii) the establishment of
      correlations between the presence of one or a group of genes (or proteins) with
      clinical outcome; and (iii) the analysis of global regulatory circuits or
      responses to the extracellular signals. The response of host cells to H. pylori
      infection will be developed in the chapter 'H. pylori and gastric malignancies'
      by Sepulveda and Coehlo. Despite our knowledge of the H. pylori genome, the
      function of about one third of its total proteins is still unknown. Functional
      genomics are straightforward approaches for the identification of new gene
      functions or metabolic pathways as well as for the understanding of cellular
      processes and the detection of new virulence factors. In silico studies combined
      with experimental work will undoubtedly continue to develop. To date, the
      expansion of proteomics with refinements in mass spectrometry technology has
      illustrated that through immunoproteomics and comparative studies, relevant novel
      antigens can be identified. Genomics not only provides invaluable information on
      H. pylori but also opens new perspectives for diagnostic or therapeutic
      applications.

PMID- 12197900
TI  - Interference of PR3-ANCA with the enzymatic activity of PR3: differences in
      patients during active disease or remission of Wegener's granulomatosis.
AB  - Anti-neutrophil cytoplasmic antibodies (ANCA) against proteinase 3 (PR3) are
      strongly associated with Wegener's granulomatosis (WG) and are thought to be
      involved in its pathogenesis. Levels of PR3-ANCA do not always correspond to
      clinical disease activity. To investigate the relationship between functional
      effects of PR3-ANCA and disease activity, we tested the effect of IgG samples
      from sera of 43 WG patients, taken during active disease or remission, for their
      capacity to interfere with the proteolytic activity of PR3. Furthermore,
      longitudinal sera of seven WG patients were included. The enzymatic activity of
      PR3 was determined (1) with casein or with a small synthetic substrate and (2) by
      complexation of PR3 with alpha1-antitrypsin (alpha1-AT). With a fixed
      concentration (100 microg/ml) of IgG, PR3-ANCA from patients during an active
      phase of WG had a higher inhibitory capacity towards the proteolytic activity of
      PR3 and complexation of PR3 with alpha1-AT than did PR3-ANCA from WG patients
      during remission. However, the number of PR3-ANCA units that gave 50% inhibition
      of the PR3 enzymatic activity and its complexation with alpha1-AT was lower for
      patients during remission than for patients during an active phase of WG,
      indicating a stronger inhibitory capacity at a molar base. In conclusion, PR3
      ANCA from patients during remission had a relatively higher inhibitory capacity
      towards the enzymatic activity of PR3 than PR3-ANCA from patients during an
      active phase. This may indicate that during active disease the ANCA titre is
      increased, but the number of active ANCA molecules that recognize the enzyme
      inhibiting epitopes is not increased.

PMID- 12197904
TI  - Epidemiology and diagnosis of Helicobacter pylori infection.
AB  - There have been no major breakthroughs in the field of epidemiology and diagnosis
      of Helicobacter pylori infection over the last year, thus for this reason, these
      two topics will be treated in the same chapter. Information on the incidence of
      infection, as in the study of Malaty et al. are now being published from long
      term cohort follow-ups. The route of transmission of H. pylori remains
      controversial, with circumstantial evidence for infection via exposure to
      animals, contaminated water supplies and oral reservoirs being reported. The
      value of citric acid to improve urea breath test (UBT) results has been
      documented. A novel stool test has been released on the market and we are
      awaiting more information, while detection of antibodies in urine gave
      satisfactory results. However, the most interesting data comes from the study of
      McColl et al. who clearly proved on a large sample and a 1-year follow-up that
      the 'test and treat' strategy using UBT, as proposed in the Maastricht Consensus
      Report, is definitely the method to use.

PMID- 12197905
TI  - Pathogenesis of Helicobacter pylori infection.
AB  - Five years after publication of the complete genome sequence of Helicobacter
      pylori, research interest is shifting from the descriptive association of
      virulence factors with clinical outcome in infected patients to the molecular
      mechanisms of virulence factor action. This is particularly noticeable for VacA
      and CagA, for both of which detailed understanding of the interaction with host
      signalling pathways has accumulated over the last year. The role of H. pylori
      Lewis antigens for clinical outcome was further substantiated. Various strategies
      of H. pylori to fool or evade the human immune system are described, which all
      lead to the dysfunction of specific compartments of the host cellular immune
      system. Finally, a number of animal models indicate that inflammation is a key
      factor for gastric carcinogenesis, which is finally supported by a large
      prospective study identifying corpus atrophy and intestinal metaplasia as
      precancerous conditions.

PMID- 12197906
TI  - Helicobacter pylori inflammation and immunity.
AB  - Gastric inflammation is a significant contributor to the disease process
      associated with Helicobacter pylori infection. It appears that both bacterial
      genes and differential host responses make interrelated contributions to
      gastritis and disease outcome after H. pylori infection. While the cag
      pathogenicity island (PAI) continues to be a focus for much of this investigation
      on the bacterial side, other bacterial genes/proteins are certainly important as
      well. On the host cell side, significant progress is being made defining the
      eucaryotic signaling cascades induced after host cells interact with H. pylori.
      The role of host cell cytokines, gastric acid, and mast cells is also being
      actively studied. Prospects for control of H. pylori associated disease continue
      to include vaccination. The mechanism(s) for vaccine-mediated control of H.
      pylori infection and disease remain ill-defined but recent evidence from animal
      models suggests that the inflammatory response may be involved. Manipulating the
      host response to H. pylori infection in humans to take advantage of the possible
      beneficial effects of inflammation, while minimizing its detrimental effects is a
      significant challenge for the future.

PMID- 12197907
TI  - Helicobacter pylori and nonmalignant disease.
AB  - Helicobacter pylori eradication has become the recognized standard and widely
      adopted therapy to cure peptic ulcer disease. Other H. pylori associated
      conditions with potential benefit from eradication therapy are still subject to
      clinical investigations. The current state of evidence for these indications is
      summarized in this article. For NSAID associated peptic ulcer disease the current
      evidence needs to be grouped in three subsets of clinical conditions: a) H.
      pylori eradication for prevention of ulcers before starting NSAIDs therapy is
      advisable; b) eradication during PPI treatment for NSAID associated active ulcer
      shows no advantage on healing; and c) eradication alone is not sufficient for
      secondary prevention of ulcer complications induced by NSAID, however it appears
      to protect from further episodes of aspirin induced bleeding. In nonulcer
      dyspepsia the latest Cochrane collaboration review supports a small benefit in
      favour of H. pylori eradication. New insight in the relationship of H. pylori
      with GERD is provided from clinical trials which show that H. pylori eradication
      does not influence the clinical course of patients with reflux esophagitis.
      Finally important new data are presented regarding the management of dyspepsia at
      the primary care level with the confirmation that the H. pylori 'test and treat'
      strategy in the appropriate setting is more cost-effective than endoscopy.

PMID- 12197908
TI  - Helicobacter pylori and gastric malignancies.
AB  - The epidemiological link of Helicobacter pylori and gastric carcinoma was
      confirmed and the reported rate of gastric carcinoma development in the Japanese
      population with H. pylori gastritis was 2.9% during a 7.8-year period. Studies
      showed that gastric atrophy and intestinal metaplasia may partially regress after
      H. pylori eradication, but whether this will result in a decrease in the
      development of malignant lesions remains to be confirmed in large studies. Little
      progress was made towards the identification of criteria applicable to
      individualized populations that would benefit from H. pylori screening and
      surveillance of gastric malignancy. Studies of low-grade MALT lymphoma reported
      clinical and molecular features that may be useful to identify cases that may be
      responsive to H. pylori eradication therapy, namely evaluation of lymphoma stage
      by EUS and t(11;18). The role of H. pylori eradication therapy in high-grade MALT
      lymphoma needs to be evaluated in larger prospective studies. The application of
      methods of global analysis of gene expression (microarray studies) resulted in
      the explosion of information on the molecular pathways activated by H. pylori in
      gastric epithelial cells. New pathways that may play an important role in H.
      pylori carcinogenesis have been discovered in several studies.

PMID- 12197909
TI  - Helicobacter pylori: the challenge in therapy.
AB  - For the therapeutic management of Helicobacter pylori infection, the Maastricht 2
      2000 Consensus Report have introduced the concept of the 'treatment package' that
      considers first- and second-line eradication therapies together. According to
      this consensus statement, the first-line therapy for H. pylori eradication is a
      combination of the proton pump inhibitors (PPI) or ranitidine bismuth citrate
      (RBC) and claritromycin plus either amoxicillin or metronidazole. The second-line
      treatment is suggested to be PPI-quadruple therapy for a minimum of 7 days. If
      bismuth compounds are not available, PPI-based triple therapy will have to be
      used as a second-line treatment only after susceptibility testing. Since no
      considerable progress has been made during the past year in treatment regimens,
      there is still a need for new compounds that are specific for H. pylori, which
      could constitute future therapies.

PMID- 12197910
TI  - Helicobacter pylori infection in pediatrics.
AB  - In the past year the main interest was focused on the role of family for
      transmission of Helicobacter pylori to children; the evaluation of noninvasive
      diagnostic tests, especially in young children; extra-intestinal clinical
      manifestations; the lack of consensus on treatment; and the problem of high
      resistance of the microorganism to antibiotics.

PMID- 12197911
TI  - Helicobacter pylori infection in geriatrics.
AB  - The prevalence of Helicobacter pylori infection increases with age worldwide.
      However, the percentage of H. pylori-positive elderly patients who are tested and
      treated for their infection remains very low. We now have data that demonstrate
      the benefit of curing H. pylori infection in elderly patients with H. pylori
      associated peptic ulcer disease and severe chronic gastritis. Furthermore, the
      cure of H. pylori may prevent progression of intestinal metaplasia and gastric
      atrophy. Studies are needed to clarify the role of eradication for elderly
      patients who have nonulcer dyspepsia, gastroesophageal reflux disease and who use
      nonsteroidal anti-inflammatory drugs. H. pylori infection may be easily diagnosed
      by histological evaluation, rapid urease test or culture performed on gastric
      biopsies taken during endoscopy. However, the biopsy site must be carefully
      selected in elderly patients. For noninvasive monitoring of H. pylori infection
      after treatment, the 13C-urea breath test has significantly higher accuracy than
      serology in the elderly. The role of the H. pylori stool antigen test in old age
      still needs to be clarified. One-week PPI-based triple therapy regimens including
      clarithromycin, amoxycillin and/or nitroimidazoles are highly effective and well
      tolerated in elderly patients. Low doses of both PPIs and clarithromycin (in
      combination with standard doses of amoxycillin or nitroimidazoles) are
      sufficient. Antibiotic resistance and low compliance are the main factors related
      to treatment failure at any age.

PMID- 12197923
TI  - End-stage renal disease in the developing world.

PMID- 12197912
TI  - Extragastric Helicobacter species.
AB  - The genus Helicobacter has expanded at a rapid pace and no fewer than 31 species
      have been named since the proposal of the genus in 1989. Of these 31 species, 22
      are principally associated with extragastric niches and there is increasing
      interest in the role of these taxa in diseases of humans and animals. Substantial
      evidence attests to certain species playing a role in the pathogenesis of
      enteric, hepatic and biliary disorders and some taxa demonstrate zoonotic
      potential. The importance of extragastric Helicobacters is likely to be an
      important topic for research in the near future. Here, important papers published
      in the field this last year are reviewed.

PMID- 12197924
TI  - Overview: end-stage renal disease in the developing world.
AB  - Although the vast majority of patients with end-stage renal disease (ESRD)
      worldwide live in what is called the developing world, little is known about its
      epidemiology and management. With the current paucity of credible and adequately
      representative registries, it is justified to resort to innovative means of
      obtaining information. In this attempt, world-renowned leading nephrologists in
      10 developing countries collaborated in filling a 103-item questionnaire
      addressing epidemiology, etiology, and management of ESRD in their respective
      countries on the basis of integrating available data from different sources.
      Through this joint effort, it was possible to identify a number of important
      trends. These include the expected high prevalence of ESRD, despite the limited
      access to renal replacement therapy, and the dependence of prevalence on wealth.
      Glomerulonephritis, rather than diabetes, remains as the main cause of ESRD with
      significant geographical variations in the prevailing histopathological types.
      The implementation of different modalities of renal replacement therapy (RRT) is
      inhibited by the lack of funding, although governments, insurance companies, and
      donations usually constitute the major sponsors. Hemodialysis is the preferred
      modality in most countries with the exception of Mexico where chronic ambulatory
      peritoneal dialysis (CAPD) takes the lead. In several other countries, dialysis
      is available only for those on the transplant waiting list. Dialysis is
      associated with a high frequency of complications particularly HBV and HCV
      infections. Data on HIV are lacking. Aluminum intoxication remains as a major
      problem in a number of countries. Treatment withdrawal is common for
      socioeconomic reasons. Transplantation is offered to an average of 4 per million
      population (pmp). Recipient exclusion criteria are minimal. Donor selection
      criteria are generally loose regarding tissue typing, remote viral infection,
      and, in some countries, blood-relation to the recipient in live-donor
      transplants. Cadaver donors are accepted in many countries participating in this
      survey. Treatment outcomes with different RRT modalities are, on the average,
      inferior to the internationally acknowledged standards largely due to infective
      and cardiovascular complications.

PMID- 12197925
TI  - End-stage renal disease and its treatment in Venezuela.
AB  - In Venezuela there are 3234 new cases (132 per million population [pmp])
      requiring renal replacement therapy each year, and only 40% of these are admitted
      to the different modalities of dialysis. In the year 2000, there were 195
      patients pmp in chronic hemodialysis (4700 patients). Diabetes, glomerular
      diseases, and hypertension account for more than 60% of the patients in chronic
      dialysis. Gross mortality in hemodialysis is around 20%, and cardiovascular
      causes are the primary cause of death (39.5%). Hospital admission in the dialysis
      patients amounts to 4.6 days/patient/year. Rehabilitation is inadequate. Only 45%
      of the dialysis patients report normal home or work activities. Transplantation
      in Venezuela has a general graft survival rate of 83% at 1 year (90% for living
      related grafts) and 50% (64% for living related grafts) at 10 years. Future
      tendencies include emphasis in preventive strategies, including early detection
      and treatment of diabetes and hypertension, as well as efforts to increase the
      rate of renal transplantation.

PMID- 12197926
TI  - Peritoneal dialysis in the developing world: the Mexican scenario.
AB  - In the developing countries it is not possible to determine the total amount of
      money spent in the treatment of chronic diseases, and the practice of renal
      replacement therapies faces many obstacles. In Mexico, the introduction of
      continuous ambulatory peritoneal dialysis and continuous cycling peritoneal
      dialysis (CCPD) achieved very good results. Unfortunately, renal disease still
      affected as much as 95% of chronic renal failure patients and it became a
      disaster with an annual mortality rate higher than 60%. This was known as the
      Mexican Model which failed in establishing peritoneal dialysis as the only
      procedure for treating patients. In order to avoid a similar scenario with the 2
      replacement therapies, we created the Official Norm for hemodialysis, and now we
      are experimenting with an increase from 5% to 20% of hemodialysis patients who
      are receiving therapy, principally in private units that attend Social Security
      patients. In addition, the government has established a Council for
      Transplantation that acts as a regulatory board. In other words, we are in the
      process of making chronic renal diseases a priority within the National Program.

PMID- 12197927
TI  - Comorbidities in patients with end-stage renal disease in developing countries.
AB  - Patients with end-stage renal disease (ESRD) who are on renal replacement therapy
      (RRT) usually have a certain number of comorbid factors. Cardiovascular diseases
      are the most common comorbidities and the most common causes of mortality in ESRD
      patients. Noncardiovascular comorbid factors including nutrition also have impact
      on survival of ESRD patients on RRT. There are scarce data regarding comorbidity
      in developing countries. Available data have shown that hypertension, diabetes,
      and various cardiovascular disorders are the leading comorbidities. Improvement
      in outcome for ESRD patients would depend on improving quality in RRT as well as
      a better understanding and management of comorbid conditions.

PMID- 12197928
TI  - Nutritional problems associated with end-stage renal disease in the developing
      world.
AB  - Protein-energy malnutrition is a major problem in dialysis patients. There is
      increased morbidity and mortality in dialysis patients with malnutrition. There
      are very few published studies on nutritional parameters and adequacy of dialysis
      from the developing world and especially from Africa. There was a significant
      improvement in neuromuscular function and nutrition in 22 hemodialysis patients
      in Egypt with optimization of dialysis dose and nutritional status. In a study of
      82 continuous ambulatory peritoneal dialysis (CAPD) patients in Durban, South
      Africa, there was a reduction in the number of hospital admissions in adequately
      dialyzed patients (achieving Kt/V of >2.1). In another study of 84 CAPD patients
      from the same center, 76.2% of patients were assessed as being malnourished, with
      loss of appetite being an important etiological factor. Strategies to optimize
      dialysis dose, together with services of a renal dietician, will assist in
      improving the nutrition of patients with chronic renal failure.

PMID- 12197929
TI  - Anemia and end-stage renal disease in the developing world.
AB  - In developing countries, multiple comorbidities such as malnutrition,
      parasitoses, and hemoglobinopathies contribute to the aggravation of anemia
      observed in patients with end-stage renal diseases. We analyze here the results
      of a retrospective evaluation of red-cells indices and iron parameters conducted
      at the end of December 2000 in 304 prevalent Tunisian patients (sex ratio, 1.05;
      mean age, 53.7 years) receiving chronic hemodialysis for a median duration of
      49.6 months (range, 1.6 to 278). Anemia, observed in 87.8% of patients, was
      normochromic and normocytic in 73% of cases. Only 2% of patients had microcytic
      and hypochromic anemia. Iron deficiency was observed in 21.6% of anemic patients.
      The mean rate of hemoglobin was significantly higher in men and in patients with
      polycystic kidney disease as the cause of renal failure. There was a positive
      correlation between hemoglobin values and the quality of dialysis. Only 10.8% of
      patients were on recombinant human erythropoietin (rHuEPO) and 38% required
      regular transfusions. We conclude that anemia observed in our patients had, in
      most cases, the characteristics of renal anemia and could be attributed to a
      deficit of renal production of erythropoietin. However, for financial reasons,
      prescription of rHuEPO is rather restrictive and blood transfusion remains
      largely used. The nephrology community and dialysis providers should increase
      their efforts to improve the anemia care of dialyzed patients in developing
      countries.

PMID- 12197930
TI  - Hypertension and end-stage renal disease in the developing world.
AB  - Hypertension is an important primary etiology of end-stage renal disease as well
      as a major factor responsible for progression of renal disease due to other
      causes. Multiple genetic and environmental factors are responsible for the
      variable prevalence of hypertension in various parts of the world. Although the
      frequency of hypertension awareness and control is very modest in the developing
      world, nephroangiosclerosis seems to be more common in the developed countries.
      Factors responsible for this discrepancy as well as various strategic measures to
      control hypertension and its impact on renal disease are discussed.

PMID- 12197931
TI  - Renal osteodystrophy in developing countries.
AB  - There are distinct differences between developing and developed countries
      regarding the pathogenesis and management of renal osteodystrophy. Such
      differences are due to ethnic factors, dialysis quality, types of membranes,
      dialysate water, lack of technical facilities to perform bone biopsies, beta2
      microglobulin, aluminium and strontium toxicity, and iron overload as well as
      economic factors hampering the use of effective yet more expensive phosphate
      binders and active vitamin D. The prevalence of renal osteodystrophy in
      developing countries is higher than in developed countries. It ranges from 24.4%
      to 63%. Aluminium related bone disease is a common cause. High strontium levels
      and iron overload in developing countries play a major role in the development of
      renal bone disease among dialysis patients.

PMID- 12197932
TI  - Posttransplant infections in the tropical countries.
AB  - Over half of all renal transplant recipients in the tropical countries develop a
      serious infection at some point in the posttransplant period and 20% to 40% of
      them succumb to these infections. Many of these infections are endemic to the
      region. A multitude of factors including unhygienic conditions, hot and humid
      climate, late presentation, lack of knowledge about the spectrum of organisms in
      these areas, scanty diagnostic techniques, and high cost of lifesaving
      antimicrobial agents contribute to this dismal outcome. Tuberculosis is observed
      in 10% to 15% of transplant recipients. Pleuropulmonary disease is most frequent,
      but the commonly employed tests are seldom helpful in the diagnosis.
      Bronchoalveolar lavage is very sensitive in early detection of this infection and
      allows timely institution of specific therapy. Hepatitis virus infections are
      generally acquired before transplant, and viral replication is accelerated under
      the effect of immunosuppressive therapy leading to chronic liver disease.
      Cytomegalovirus (CMV) disease has shown a fourfold increase after introduction of
      cyclosporine to the immunosuppressive regimes at our center. Coinfection with
      other bacteria or fungi is frequent in CMV-infected allograft recipients.
      Opportunistic fungal infections are seen in less than 10% of allograft
      recipients, but this figure is likely an underestimate. The frequently
      encountered fungal infections include Candida, Aspergillus, Cryptococcus, and
      Mucor. Fungal infections carried a high mortality of over 65% at our center. The
      protean manifestations of the opportunistic infections and nonavailability of
      sensitive diagnostic tests in most centers in the underdeveloped countries often
      delay the diagnosis and institution of therapy.

PMID- 12197933
TI  - Malignant tumors after renal transplantation.
AB  - The rate of certain malignancies in renal transplant recipients is 14 to 500
      times higher than the rate in the general population. The reported prevalence
      rates for malignant tumors in various kidney recipient series range from 4% to
      18% with an average of 6%. The tumors occur in patients who are younger than
      individuals affected in the general population, and the incidence rates rise with
      each year after transplantation. Since 1975, we have recorded 52 cases of
      malignancy development in 50 (3.7%) patients who were treated with P + AZA, P +
      CsA + AZA, or P + CsA + MMF therapy (P, prednisolone; AZA, azathioprine; CsA,
      cyclosporin A; MMF, mycophenolate mofetil). In this article, 50 renal transplant
      recipients who developed malignancy and were followed by the Transplantation
      Center at Baskent University Faculty of Medicine were analyzed. Analysis revealed
      that patients who received CsA had a higher incidence of Kaposi's sarcoma than
      those who received the standard regimen. Regarding other tumor types, our results
      showed no statistical differences among the incidence rates in the different
      treatment groups.

PMID- 12197934
TI  - Recruiting the community for supporting end-stage renal disease management in the
      developing world.
AB  - Although the incidence of new end-stage renal disease (ESRD) patients in Pakistan
      is estimated at 100 patients per million (ppm), the prevalence of those alive on
      renal replacement therapy (RRT) is around 40 ppm, reflecting the severe shortage
      of facilities. A national program was launched in 1998 to provide free RRT, but
      the funds were extremely limited, leading to the flourishing of suboptimal
      treatment in private dialysis and transplant centers. The Sindh Institute of
      Urology and Transplantation (SIUT), started as a small unit in 1975, took the
      lead in recruiting nongovernmental funds for RRT. Through the devotion of several
      groups, it was possible to raise funds from individuals, pharmaceutical firms,
      and other organizations, which permitted the development of SIUT into an
      independent, large, and fully equipped institution that provides free RRT
      including dialysis and transplantation to many thousands of patients. This
      prompted the government to increase its contributions to encourage SIUT to pursue
      its unique path.

PMID- 12197935
TI  - Numerical investigation of the effect of blade geometry on blood trauma in a
      centrifugal blood pump.
AB  - Fluid dynamic forces in centrifugal blood pump impellers are of key importance in
      destruction of red blood cells (RBCs) because high rotational speed leads to
      strong interaction between the impeller and the RBCs. In this paper, three
      dimensional models of five different blade geometries are investigated
      numerically using the commercial software CFX-TASCflow, and the streaklines of
      RBCs are obtained using the Lagrangian particle tracking method. In reality, RBCs
      pass through the pump along complicated paths resulting in a highly irregular
      loading condition for each RBC. In order to enable the prediction of blood damage
      under the action of these complex-loading conditions, a cumulative damage model
      for RBCs was adopted in this paper. The numerically simulated percent hemoglobin
      (%HB) released as RBCs traversed the impeller and volute was examined. It was
      observed that the residence time of particles in the blade passage is a critical
      factor in determining hemolytic effects. This, in turn, is a function of the
      blade geometry. In addition, it was observed that the volute profile is an
      important influence on the computed HB% released.

PMID- 12197936
TI  - Coronary artery bypass grafting in patients on chronic hemodialysis: diabetic
      nephropathy versus nondiabetic nephropathy.
AB  - Patients with both end-stage renal disease and diabetes mellitus carry an
      increased risk of coronary atherosclerosis. This study was performed to evaluate
      the perioperative and remote outcome of diabetic nephropathy patients on
      hemodialysis undergoing coronary artery bypass grafting (CABG). We
      retrospectively analyzed the results of CABG performed between September 1, 1993
      and August 31, 2001. Preoperative, perioperative, and follow-up data of patients
      with hemodialysis primarily due to diabetic nephropathy (Group D, n = 31, 22
      males and 9 females with a mean age of 60.1 +/- 6.6) were collected and compared
      to patients with hemodialysis primarily due to nondiabetic nephropathy (group N,
      n = 21, 17 males and 4 females with a mean age of 60.9 +/- 11.2). Preoperative
      risk factors between the 2 groups were not significantly different. The mean
      number of distal anastomoses was 2.5 +/- 1.2 in Group D and 2.5 +/- 1.0 in Group
      N (p = not significant [NS]). All patients received at least 1 internal mammary
      artery graft. There was 1 in-hospital death in each group. Postoperative
      recovery, mortality, and morbidity were not significantly different between the
      two groups. At the mean follow-up of 2.7 years, the actuarial 3 year survival
      rate was 72.8% in Group D and 78.7% in Group N (p = NS). The actuarial 3 year
      cardiac event-free rate was 79.7% in Group D and 74.7% in Group N (p = NS). CABG
      for hemodialysis patients can be performed with acceptable risks. Diabetic
      nephropathy has no impact on early or remote patient outcomes among patients on
      hemodialysis.

PMID- 12197937
TI  - Chordal-sparing mitral valve replacement using artificial chordae tendineae for
      rheumatic mitral stenosis: experience of the "oblique" method.
AB  - Chordal-sparing mitral valve replacement (CSMVR) has been proven to be beneficial
      for postoperative left ventricular (LV) function. In patients with mitral
      stenosis, however, diseased chordae tendineae (CT) often have to be replaced
      using artificial CT to achieve CSMVR. Previously, we reported that resusupension
      of artificial CT in an oblique direction enhances systolic LV function. Among 40
      consecutive patients with mitral valve replacement (MVR), 17 (4 men and 13 women;
      mean age 66.5 years) with rheumatic mitral stenosis underwent CSMVR with oblique
      resuspension. Echocardiography was done before the operation, early (mean 25
      days) after the operation, and at a late stage (mean 14 months). There was no
      mortality or major morbidity. LV ejection fraction late after the operation (68
      +/- 8%) was better than that in the early period (61 +/- 8%, p < 0.01), and
      comparable to the preoperative level (65 +/- 9%). The oblique method may help to
      improve the results of MVR.

PMID- 12197938
TI  - Artificial mimicking of physiological active transport by a membrane co-cultured
      with two different cells: hepatic origin HepG2 and renal origin PCTL-MDR.
AB  - We designed a membrane culture unit on which 2 different cell lines were co
      cultured to achieve selective and active transport of toxins. Hepatic origin
      HepG2 and renal origin multidrug-resistant gene-transduced proximal convoluted
      tubular cell line (PCTL-MDR) were cultured on the opposite sides of an expanded
      polytetrafluoroethylene membrane. The activity of testosterone hydroxylation by
      original HepG2 was very low; however, the cytochrome p450 (CYP) 3A4-transduced
      recombinant HepG2 metabolized the substrate efficiently. Testosterone added into
      the outer medium was hydrolyzed by HepG2, and the metabolites were preferentially
      transported to the inner medium by PCTL-MDR. [3H]-digoxin and [14C]-inulin were
      added to the outer medium; the digoxin was transported from the outer to inner
      space through the cell monolayer but the inulin was not, suggesting that the
      membrane actively transported only the substrate of the channel protein, MDR. The
      cells were irradiated (10 Gy) to prevent a membrane leak due to overgrowth. The
      irradiation did not induce apoptosis but resulted in long-lasting membrane
      function without leakage. The membrane co-cultured with hepatic and renal origin
      cells will enable a novel hemofiltration system with selective and active
      transport activities.

PMID- 12197939
TI  - The alphabet of research on pulsatile and nonpulsatile (continuous flow)
      perfusion during chronic support.

PMID- 12197943
TI  - Pryogen retention by highly permeable synthetic membranes during in vitro
      dialysis.

PMID- 12197941
TI  - Determination of arterial blood ammonia in uremic patients before and after
      hemodialysis using three different ammonia methods.

PMID- 12197944
TI  - A new automated method for the determination of the Total Antioxidant Capacity
      (TAC) of human plasma, based on the crocin bleaching assay.
AB  - BACKGROUND: Antioxidant molecules, which scavenge free radical species to prevent
      or delay oxidative damage of important macromolecules, membrane lipids and
      lipoproteins, are prevalent in plasma and other biological fluids. Among them,
      bilirubin, uric acid and protein thiols are the major endogenous antioxidants,
      while vitamins C and E, as well as a number of food-derived (poly)aromatic
      substances, belonging to stilbens, flavonoids and phenolic acids, are the main
      classes of nutritional antioxidants. Assays for total antioxidant capacity in
      plasma differ in their type of oxidation source, target and measurement used to
      detect the oxidized product. METHODS: In the present work we present an automated
      assay for the estimation of blood total antioxidant capacity (TAC assay), based
      on the crocin bleaching (oxidation) method. This method was adapted on a modern
      autoanalyzer, was linear over a wide range of values (0-3 mmol/L), and performed
      using an end point measurement. RESULTS: The TAC method presented a linear
      correlation with another automated commercial Total Antioxidant Status (TAS)
      test. Detection of the interference of different metabolites revealed a
      significant participation of TAC from uric acid, bilirubin, albumin, a minor
      interference from ascorbic acid, and no interference from hemoglobin. TAC was not
      modified by two freeze/thawing cycles, and was stable in samples stored at room
      temperature for 4 hours. K-EDTA and heparin were the best anticoagulants, while
      citrate decreased TAC by 20%. Reference values derived from samples of normal
      blood donors was 1.175 PlusMinus; 0.007 mmol/L (mean PlusMinus; SEM), while a
      diet rich in antioxidants more than doubled this value. CONCLUSIONS: The proposed
      TAC assay, is fully automated, stable and reliable, and could be of value in the
      estimation of the AC of plasma. It is further proposed to calculate the
      antioxidant capacity of plasma after a subtraction of all interference deriving
      from endogenous and/or exogenous metabolites. The antioxidant capacity of plasma
      thus calculated can be used as a useful indicator of the antioxidant value of
      foods and beverages in the daily diet.

PMID- 12197945
TI  - Short-term LDL cholesterol-lowering efficacy of plant stanol esters.
AB  - BACKGROUND: The short-term cholesterol-lowering efficacy of plant stanol esters
      has been open to debate, and the data from different clinical studies with
      hypercholesterolemic subjects are variable, partly due to lack of systematic
      studies. Therefore, we investigated the time in days needed to obtain the full
      cholesterol-lowering effect of stanol esters in hypercholesterolemic subjects.
      METHODS: Eleven mildly to moderately hypercholesterolemic subjects consumed
      stanol ester margarine (2.0 g/day of stanols) as a part of their habitual diet
      for 14 days and the changes in serum lipid values were measured three times at 4,
      8 and 15 days after the initiation of test margarine consumption (0 day). The
      returning of serum lipid concentrations to baseline was measured two times after
      2 or 3 days and after 7 days of the end of the test margarine consumption.
      RESULTS: Serum LDL cholesterol concentrations were reduced from 0 day (4.51 +/-
      0.66 mmol/l) by 3.5% (P = ns), 9.9% (p < 0.05) and 10.2% (P < 0.05) at 4, 8 and
      15 days, respectively. Serum campesterol/total cholesterol ratio, an indirect
      marker of intestinal cholesterol absorption, was significantly reduced on day 4
      already. After ending the stanol ester use serum cholesterol concentrations began
      to return rapidly and after 7 days serum LDL cholesterol was 5.3% less than the
      initial value (P = ns). CONCLUSION: The specific effect of plant stanol esters on
      serum LDL cholesterol can fully be obtained within 1-2 weeks of the use of plant
      stanol ester-enriched margarine.

PMID- 12197946
TI  - Response of regional brain glutamate transaminases of rat to aluminum in protein
      malnutrition.
AB  - BACKGROUND: The mechanism of aluminum-induced neurotoxicity is not clear. The
      involvement of glutamate in the aluminium-induced neurocomplications has been
      suggested. Brain glutamate levels also found to be altered in protein
      malnutrition. Alterations in glutamate levels as well as glutamate-alpha
      decarboxylase in different regions of rat brain has been reported in response to
      aluminum exposure. Thus the study of glutamate metabolising enzymes in different
      brain regions of rats maintained on either normal or restricted protein diet may
      be of importance for understanding the neurotoxicity properties of aluminium.
      RESULTS: Dietary protein restrictions does not have an significant impact on
      regional aluminum content of the brain. The interaction of aluminum intoxication
      and protein restriction is significant in the thalamic area and the midbrain
      hippocampal region in cases of glutamate oxaloacetate transaminase. In the case
      of glutamate pyruvate transaminase, this interaction is significant only in
      thalamic area. CONCLUSION: The metabolism of amino acids, as indicated by
      activities of specific transaminases, of brain is altered in response to aluminum
      exposure. These alterations are region specific and are dependent on dietary
      protein intake or manipulation of the brain amino acid homeostasis.

PMID- 12197947
TI  - Diversity and abundance of bacteria in an underground oil-storage cavity.
AB  - BACKGROUND: Microorganisms inhabiting subterranean oil fields have recently
      attracted much attention. Since intact groundwater can easily be obtained from
      the bottom of underground oil-storage cavities without contamination by surface
      water, studies on such oil-storage cavities are expected to provide valuable
      information to understand microbial ecology of subterranean oil fields. RESULTS:
      DNA was extracted from the groundwater obtained from an oil-storage cavity
      situated at Kuji in Iwate, Japan, and 16S rRNA gene (16S rDNA) fragments were
      amplified by PCR using combinations of universal and Bacteria-specific primers.
      The sequence analysis of 154 clones produced 31 different bacterial sequence
      types (a unique clone or group of clones with sequence similarity of > 98). Major
      sequence types were related to Desulfotomaculum, Acetobacterium, Desulfovibrio,
      Desulfobacula, Zoogloea and Thiomicrospira denitrificans. The abundance in the
      groundwater of bacterial populations represented by these major sequence types
      was assessed by quantitative competitive PCR using specific primers, showing that
      five rDNA types except for that related to Desulfobacula shared significant
      proportions (more than 1%) of the total bacterial rDNA. CONCLUSIONS: Bacteria
      inhabiting the oil-storage cavity were unexpectedly diverse. A phylogenetic
      affiliation of cloned 16S rDNA sequences suggests that bacteria exhibiting
      different types of energy metabolism coexist in the cavity.

PMID- 12197955
TI  - Women of color and end-of-life care.

PMID- 12197956
TI  - Misclassification of racial/ethnic minority deaths: the final colonization.

PMID- 12197957
TI  - Continuing increases in sexual risk behavior and sexually transmitted diseases
      among men who have sex with men: San Francisco, Calif, 1999-2001, USA.

PMID- 12197959
TI  - What's a cigarette company to do.

PMID- 12197960
TI  - Indigenous health: fulfilling our obligation to future generations.

PMID- 12197961
TI  - Health and indigenous people: recommendations for the next generation.

PMID- 12197962
TI  - The data are in: health matters in welfare policy.

PMID- 12197963
TI  - Improving the health of future generations: the Canadian Institutes of Health
      Research Institute of Aboriginal Peoples' Health.
AB  - In the past and in the present, research studies and media reports have focused
      on pathology and dysfunction in aboriginal communities and have often failed to
      present a true and complete picture of the aboriginal experience. The Canadian
      Institutes of Health Research Institute of Aboriginal Peoples' Health is a
      national strategic research initiative led by both the aboriginal and research
      communities. This initiative aims to improve aboriginal health information,
      develop research capacity, better translate research into practice, and inform
      public health policy with the goal of improving the health of indigenous peoples.

PMID- 12197964
TI  - Perspectives on American Indian health.
AB  - American Indians and Alaska Natives continue to experience significant
      disparities in health status compared with the US general population and now are
      facing the new challenges of rising rates of chronic diseases. The Indian health
      system continues to try to meet the federal trust responsibility to provide
      health care for American Indians and Alaska Natives despite significant
      shortfalls in funding, resources, and staff. New approaches to these Indian
      health challenges, including a greater focus on public health, community-based
      interventions, and tribal management of health programs, provide hope that the
      health of Indian communities will improve in the near future.

PMID- 12197965
TI  - The melting ice cellar: what native traditional knowledge is teaching us about
      global warming and environmental change.
AB  - Environmental problems have often been observed by Alaska Native communities
      decades before they have been confirmed by scientific research.

PMID- 12197966
TI  - The history of uranium mining and the Navajo people.
AB  - From World War II until 1971, the government was the sole purchaser of uranium
      ore in the United States. Uranium mining occurred mostly in the southwestern
      United States and drew many Native Americans and others into work in the mines
      and mills. Despite a long and well-developed understanding, based on the European
      experience earlier in the century, that uranium mining led to high rates of lung
      cancer, few protections were provided for US miners before 1962 and their
      adoption after that time was slow and incomplete. The resulting high rates of
      illness among miners led in 1990 to passage of the Radiation Exposure
      Compensation Act.

PMID- 12197967
TI  - Public health service dentist examines an Alaska native child, 1951.

PMID- 12197968
TI  - Occupational injury and illness surveillance: conceptual filters explain
      underreporting.
AB  - Occupational health surveillance data are key to effective intervention. However,
      the US Bureau of Labor Statistics survey significantly underestimates the
      incidence of work-related injuries and illnesses. Researchers supplement these
      statistics with data from other systems not designed for surveillance. The
      authors apply the filter model of Webb et al. to underreporting by the Bureau of
      Labor Statistics, workers' compensation wage-replacement documents, physician
      reporting systems, and medical records of treatment charged to workers'
      compensation. Mechanisms are described for the loss of cases at successive steps
      of documentation. Empirical findings indicate that workers repeatedly risk
      adverse consequences for attempting to complete these steps, while systems for
      ensuring their completion are weak or absent.

PMID- 12197969
TI  - Improving the health of workers in indoor environments: priority research needs
      for a national occupational research agenda.
AB  - Indoor nonindustrial work environments were designated a priority research area
      through the nationwide stakeholder process that created the National Occupational
      Research Agenda. A multidisciplinary research team used member consensus and
      quantitative estimates, with extensive external review, to develop a specific
      research agenda. The team outlined the following priority research topics:
      building-influenced communicable respiratory infections, building-related
      asthma/allergic diseases, and nonspecific building-related symptoms; indoor
      environmental science; and methods for increasing implementation of healthful
      building practices. Available data suggest that improving building environments
      may result in health benefits for more than 15 million of the 89 million US
      indoor workers, with estimated economic benefits of $5 to $75 billion annually.
      Research on these topics, requiring new collaborations and resources, offers
      enormous potential health and economic returns.

PMID- 12197970
TI  - Changes in use of health insurance and food assistance programs in medically
      underserved communities in the era of welfare reform: an urban study.
AB  - OBJECTIVES: The purpose of this study was to assess changes in health insurance
      and food assistance enrollment following passage of the Personal Responsibility
      and Work Opportunity Reconciliation Act of 1996. METHODS: Extant data sources
      were used to calculate changes in Temporary Assistance for Needy Families (TANF),
      Medicaid, and Food Stamp program enrollment in medically underserved Manhattan
      communities after 1996. RESULTS: Dramatic declines in TANF enrollment were
      accompanied by declines in Food Stamp program enrollment and a deceleration in
      Medicaid enrollment among several communities. CONCLUSIONS: As the Personal
      Responsibility and Work Opportunity Reconciliation Act comes up for
      reauthorization later in 2002, policymakers should revise legislation so that
      needy families do not lose health insurance or food assistance support.

PMID- 12197971
TI  - Relationships between welfare status, health insurance status, and health and
      medical care among children with asthma.
AB  - OBJECTIVES: This study evaluated the relationships between health insurance and
      welfare status and the health and medical care of children with asthma. METHODS:
      Parents of children with asthma aged 2 to 12 years were interviewed at 6 urban
      clinical sites and 2 welfare offices. RESULTS: Children whose families had
      applied for but were denied welfare had more asthma symptoms than did children
      whose families had had no contact with the welfare system. Poorer mental health
      in parents was associated with more asthma symptoms and higher rates of health
      care use in their children. Parents of uninsured and transiently insured children
      identified more barriers to health care than did parents whose children were
      insured. CONCLUSIONS: Children whose families have applied for welfare and
      children who are uninsured are at high risk medically and may require additional
      services to improve health outcomes.

PMID- 12197972
TI  - Employment barriers among welfare recipients and applicants with chronically ill
      children.
AB  - OBJECTIVES: This study evaluated the association of chronic child illness with
      parental employment among individuals who have had contact with the welfare
      system. METHODS: Parents of children with chronic illnesses were interviewed.
      RESULTS: Current and former welfare recipients and welfare applicants were more
      likely than those with no contact with the welfare system to report that their
      children's illnesses adversely affected their employment. Logistic regression
      analyses showed that current and former receipt of welfare, pending welfare
      application, and high rates of child health care use were predictors of
      unemployment. CONCLUSIONS: Welfare recipients and applicants with chronically ill
      children face substantial barriers to employment, including high child health
      care use rates and missed work. The welfare reform reauthorization scheduled to
      occur later in 2002 should address the implications of chronic child illness for
      parental employment.

PMID- 12197974
TI  - Welfare to work? Impact of maternal health on employment.
AB  - OBJECTIVES: This study investigated whether health problems among poor mothers of
      chronically ill children affect their ability to obtain and maintain employment.
      METHODS: Mothers of children with chronic illnesses were surveyed at clinical and
      welfare agency sites in San Antonio, Tex. RESULTS: There were distinct health
      differences according to mothers' TANF and employment status. Mothers without
      TANF experience reported better physical and mental health and less domestic
      violence and substance use than did those who had TANF experience. Those not
      currently working had higher rates of physical and mental health problems.
      CONCLUSIONS: Poor maternal health is associated with need for cash assistance and
      health insurance. Policymakers must recognize that social policies promoting
      employment will fail if they do not address the health needs of poor women and
      children.

PMID- 12197973
TI  - Chronic illness among poor children enrolled in the temporary assistance for
      needy families program.
AB  - OBJECTIVES: This study assessed chronic child illness among recipients of
      Temporary Assistance for Needy Families (TANF) benefits and poor families not
      receiving benefits. METHODS: Data from the 1998 National Health Interview Survey
      were used to examine chronic child illness, enrollment in TANF, health insurance
      status, and selected access indicators. RESULTS: One quarter of TANF-enrolled
      children had chronic illnesses. Unenrolled children were 3 times as likely as
      TANF-enrolled children to be uninsured. Among the chronically ill, 31.7% of
      unenrolled and 14.3% of enrolled children experienced gaps in insurance coverage
      that were associated with access barriers. CONCLUSIONS: Welfare policies should
      consider the effects of chronic illness and gaps in insurance coverage on the
      health of poor children.

PMID- 12197975
TI  - Improving cancer incidence estimates for American Indians and Alaska Natives in
      the Pacific Northwest.

PMID- 12197976
TI  - Self-reported vs administrative race/ethnicity data and study results.

PMID- 12197977
TI  - Syphilis control among incarcerated men who have sex with men: public health
      response to an outbreak.

PMID- 12197978
TI  - Intake of soft drinks, fruit-flavored beverages, and fruits and vegetables by
      children in grades 4 through 6.

PMID- 12197979
TI  - Effect of low medical literacy on health survey measurements.

PMID- 12197980
TI  - Avoidable mortality in the United States and Canada, 1980-1996.

PMID- 12197981
TI  - Trends in diabetes prevalence among American Indian and Alaska native children,
      adolescents, and young adults.
AB  - OBJECTIVES: This study determined trends in diabetes prevalence among young
      American Indians and Alaska Natives. METHODS: American Indian and Alaska Native
      children (< 15 years), adolescents (15-19 years), and young adults (20-34 years)
      with diabetes were identified from the Indian Health Service (IHS) outpatient
      database. The population living within IHS contract health service delivery areas
      was determined from census data. RESULTS: From 1990 to 1998, the total number of
      young American Indians and Alaska Natives with diagnosed diabetes increased by
      71% (4534 to 7736); prevalence increased by 46% (6.4 per 1000 to 9.3 per 1000
      population). Increases in prevalence were greater among adolescents and among
      young men. CONCLUSIONS: Diabetes should be considered a major public health
      problem among young American Indians and Alaska Natives.

PMID- 12197982
TI  - Perinatal and infant health among rural and urban American Indians/Alaska
      Natives.
AB  - OBJECTIVES: We sought to provide a national profile of rural and urban American
      Indian/Alaska Native (AI/AN) maternal and infant health. METHODS: In this cross
      sectional study of all 1989-1991 singleton AI/AN births to US residents, we
      compared receipt of an inadequate pattern of prenatal care, low birthweight (<
      2500 g), infant mortality, and cause of death for US rural and urban AI/AN and
      non-AI/AN populations. RESULTS: Receipt of an inadequate pattern of prenatal care
      was significantly higher for rural than for urban mothers of AI/AN infants (18.1%
      vs 14.4%, P </=.001); rates for both groups were over twice that for Whites
      (6.8%). AI/AN postneonatal death rates (rural = 6.7 per 1000; urban = 5.4 per
      1000) were more than twice that of Whites (2.6 per 1000). CONCLUSIONS:
      Preventable disparities between AI/ANs and Whites in maternal and infant health
      status persist.

PMID- 12197983
TI  - Effectiveness of a worksite intervention to reduce an occupational exposure: the
      Minnesota wood dust study.
AB  - OBJECTIVES: This study assessed the effectiveness of an intervention to reduce
      wood dust, a carcinogen, by approximately 26% in small woodworking businesses.
      METHODS: We randomized 48 businesses to an intervention (written recommendations,
      technical assistance, and worker training) or comparison (written recommendations
      alone) condition. Changes from baseline in dust concentration, dust control
      methods, and worker behavior were compared between the groups 1 year later.
      RESULTS: At follow-up, workers in intervention relative to comparison businesses
      reported greater awareness, increases in stage of readiness, and behavioral
      changes consistent with dust control. The median dust concentration change in the
      intervention group from baseline to follow-up was 10.4% (95% confidence interval
      = -28.8%, 12.7%) lower than the change in comparison businesses. CONCLUSIONS: We
      attribute the smaller-than-expected reduction in wood dust to the challenge of
      conducting rigorous intervention effectiveness research in occupational settings.

PMID- 12197985
TI  - National health insurance, physician financial incentives, and primary cesarean
      deliveries in Taiwan.
AB  - OBJECTIVES: Taiwan's National Health Insurance Program (NHI) was implemented on
      March 1, 1995. This study analyzed the influences of the Case Payment method of
      reimbursement for inpatient care and of physician financial incentives on a
      woman's choice for primary cesarean delivery. METHODS: Logistic regressions were
      used to analyze 11 788 first-time deliveries in a nonprofit hospital system
      between March 1, 1994, and February 29, 1996. RESULTS: After implementation of
      the NHI's Case Payment scheme, the likelihood that a woman would choose primary
      cesarean delivery increased by four to five times compared with the choice
      behavior of uninsured individuals prior to NHI (P <.0001). CONCLUSION: Out-of
      pocket payment discourages the selection of primary cesarean delivery. No robust
      statistics were found relating physician financial incentives to delivery choice.

PMID- 12197984
TI  - The influence of chronic respiratory conditions on health status and work
      disability.
AB  - OBJECTIVES: This study examined the impact of asthma and chronic obstructive
      pulmonary disease (COPD) on health status and work disability. METHODS: We used
      data from a population-based sample of 3805 California adults. RESULTS: Compared
      with adults with no chronic health conditions, adults with COPD or asthma had a
      greater risk of self-reported diminished general health (odds ratio [OR] = 10.95;
      95% confidence interval [CI] = 6.31, 19.0 and OR = 3.92; 95% CI = 2.31, 6.65,
      respectively). Respondents with COPD or asthma also had worse mental health
      status, as indicated by a greater risk of depressive symptoms (OR = 10.05; 95% CI
      = 5.29, 19.08 and OR = 2.59; 95% CI = 1.33, 5.04). COPD was associated with
      reduced current employment (OR = 0.41; 95% CI = 0.24, 0.71). CONCLUSIONS: Asthma
      and COPD are associated with poor health status and greater work disability.

PMID- 12197986
TI  - Suicide and marital status in the United States, 1991-1996: is widowhood a risk
      factor?
AB  - OBJECTIVES: This study examined whether marital status is associated with suicide
      rates among various age, sex, and racial groups, in particular with widowhood
      among young adults of both sexes. METHODS: US national suicide mortality data
      were compiled for the years 1991-1996, and suicide rates were broken down by
      race, 5-year age groups, sex, and marital status. RESULTS: Data on suicide rates
      indicated an approximately 17-fold increase among young widowed White men (aged
      20-34 years), a 9-fold increase among young widowed African American men, and
      lesser increases among young widowed White women compared with their married
      counterparts. CONCLUSIONS: National data suggest that as many as 1 in 400 White
      and African American widowed men aged 20-35 years will die by suicide in any
      given year (compared with 1 in 9000 married men in the general population).

PMID- 12197988
TI  - Glutathione in kwashiorkor.

PMID- 12197989
TI  - Predicting obesity in adults from childhood and adolescent weight.

PMID- 12197987
TI  - The social-environmental context of violent behavior in persons treated for
      severe mental illness.
AB  - OBJECTIVES: This study examined the prevalence and correlates of violent behavior
      by individuals with severe mental illness. METHODS: Participants (N = 802) were
      adults with psychotic or major mood disorders receiving inpatient or outpatient
      services in public mental health systems in 4 states. RESULTS: The 1-year
      prevalence of serious assaultive behavior was 13%. Three variables-past violent
      victimization, violence in the surrounding environment, and substance abuse
      showed a cumulative association with risk of violent behavior. CONCLUSIONS:
      Violence among individuals with severe mental illness is related to multiple
      variables with compounded effects over the life span. Interventions to reduce the
      risk of violence need to be targeted to specific subgroups with different
      clusters of problems related to violent behavior.

PMID- 12197990
TI  - Tolerable upper intakes for dietary iron set by the US Food and Nutrition Board.

PMID- 12197991
TI  - Do body iron stores increase the risk of developing coronary heart disease?

PMID- 12197992
TI  - Bioconversion of vaccenic acid to conjugated linoleic acid in humans.
AB  - BACKGROUND: Vaccenic acid (11-trans octadecenoic acid; VA), a major trans fatty
      acid in the fat of ruminants, is produced in the rumen and converted in tissues
      to rumenic acid (9-cis, 11-trans octadecenoic acid; RA), an isomer of conjugated
      linoleic acid, by Delta(9)-desaturase. There are indications that this conversion
      also occurs in humans. OBJECTIVE: The aim of this controlled intervention was to
      study the conversion of VA to RA in humans after consumption of diets with
      increasing amounts of VA. DESIGN: Thirty healthy subjects consumed a baseline
      diet rich in oleic acid for 2 wk. The subjects were then divided into 3 groups (n
      = 10 per group) and provided a diet containing 1.5, 3.0, or 4.5 g VA/d for 9 d.
      All diets contained equal amounts of macronutrients and differed only in their
      fatty acid compositions. The fats were mixed into conventional foods, and nearly
      all food was provided during the study. RESULTS: The proportion of VA in serum
      total fatty acids increased 94%, 307%, and 620% above baseline with the 1.5-, 3.0
      , and 4.5-g diets, respectively. This was associated with a linear increase in
      the proportion of RA. The conversion rate was 19% on average, with significant
      interindividual differences with all 3 intakes of VA. The urinary excretion of 8
      iso-prostaglandin F(2alpha) increased in all groups (P < 0.001). CONCLUSIONS: The
      results quantify the desaturation of VA to RA in humans. Conversion is likely to
      contribute significantly to the amount of RA available to the body, and dietary
      intakes of VA should thus be taken into account when predicting RA status.

PMID- 12197994
TI  - Snacks consumed in a nonhungry state have poor satiating efficiency: influence of
      snack composition on substrate utilization and hunger.
AB  - BACKGROUND: Several epidemiologic studies suggest that snacking may play an
      etiologic role in obesity. OBJECTIVE: We assessed the behavioral and metabolic
      consequences of a high-carbohydrate (HC) or high-protein (HP) snack consumed 215
      min after lunch, thereby investigating ways that snacking in a nonhungry state
      could be involved in the etiology of obesity. DESIGN: Eight lean young men
      attended 3 sessions (basal, HP snack, and HC snack) in a counterbalanced order
      with 2 wk between sessions. During all sessions, subjects were time-blinded while
      we measured the temporal pattern of plasma glucose, insulin, and fatty acid
      concentrations; hunger ratings; substrate oxidation; and energy expenditure from
      215 min after the beginning of lunch until the spontaneous dinner request.
      RESULTS: Compared with the basal (no snack) session, the HP snack delayed the
      spontaneous dinner request (by 38 +/- 16 min, P < 0.05) but the HC snack did not.
      Energy and macronutrient intakes at dinner were unaffected by both snacks. After
      the HP snack, plasma fatty acid concentrations were lower (P < 0.05), but glucose
      and insulin were unchanged compared with the basal session. After the HC snack,
      plasma glucose and insulin concentrations were higher and plasma fatty acid
      concentrations were lower than those in the basal session (P < 0.05 for both).
      Both snacks promoted carbohydrate utilization (P < 0.05), and the HC snack
      depressed fat oxidation (P < 0.05). CONCLUSION: This study showed that a snack
      consumed in a satiety state has poor satiating efficiency irrespective of its
      composition, which is evidence that snacking plays a role in obesity.

PMID- 12197995
TI  - Predicting total energy expenditure from self-reported dietary records and
      physical characteristics in adult and elderly men and women.
AB  - BACKGROUND: Energy requirements and nutrient intakes are commonly estimated from
      self-reported dietary records, but such estimation has proven to be unreliable.
      When energy intakes determined from dietary records are compared with energy
      expenditures measured with the use of doubly labeled water, the former
      consistently underestimate energy requirements and have a high degree of
      variability. OBJECTIVE: The objective of this study was to reduce the bias and
      variability of self-reported dietary records through the use of stepwise multiple
      regression analysis to develop models that relate energy expenditure measured
      with the use of doubly labeled water to energy intake from dietary records, sex,
      and fat-free mass (or weight and height). DESIGN: Data from 54 healthy adult men
      and women were used to develop these models. RESULTS: Fat-free mass, energy
      intake, and sex accounted for 86% of the variability in energy expenditure,
      whereas energy intake, sex, height, and weight accounted for 83%. When the model
      relating fat-free mass, energy intake, and sex to energy expenditure was tested
      on published data, it reduced the bias and variability of self-reported dietary
      records from -17 +/- 27% to 3 +/- 16%. When the model relating energy intake,
      sex, weight, and height to energy expenditure was tested on published data, it
      reduced the bias and variability of self-reported dietary records from -19 +/-
      25% to -0.3 +/- 19%. CONCLUSION: Results from this study indicate that a simple
      relation can be used to correct self-reported dietary records to estimated energy
      requirements.

PMID- 12197993
TI  - Effect of protein source on resistive-training-induced changes in body
      composition and muscle size in older men.
AB  - BACKGROUND: Aging is associated with reductions in muscle mass and strength, but
      nutrition and exercise interventions can delay this progression and enhance the
      quality of life. OBJECTIVE: We examined whether the predominant source of protein
      consumed by older men influenced measures of muscle size and strength, body
      composition, resting energy expenditure, and skeletal muscle creatine
      concentrations in response to 12 wk of resistive training. DESIGN: After
      consuming a lactoovovegetarian (LOV) diet for 2 wk, 21 men aged 65 +/- 5 y were
      randomly assigned to either consume a beef-containing (BC) diet (n = 10) or to
      continue the LOV diet (n = 11) throughout resistive training. The BC diet
      included 0.6 g protein. kg(-1). d(-1) from beef and the LOV diet included 0.6 g
      protein. kg(-1). d(-1) from textured vegetable protein (soy) sources. The
      remaining protein in the diets came from self-selected LOV sources. RESULTS: The
      mean total protein intake for both groups ranged from 1.03 to 1.17 g. kg(-1). d(
      1) during the intervention. Men in both groups had improvements (14-38%) in
      maximal dynamic strength of all the muscle groups trained with no significant
      difference between groups. With resistive training, cross-sectional muscle area
      of the vastus lateralis increased in both groups (4.2 +/- 3.0% and 6.0 +/- 2.6%
      for the LOV and BC groups, respectively) with no significant difference between
      groups. Body composition, resting energy expenditure, and concentrations of
      muscle creatine, phosphocreatine, and total creatine did not differ significantly
      between groups or change over time. CONCLUSIONS: These data suggest that
      increases in muscle strength and size were not influenced by the predominant
      source of protein consumed by older men with adequate total protein intake.

PMID- 12197996
TI  - Whole-grain intake and the risk of type 2 diabetes: a prospective study in men.
AB  - BACKGROUND: Certain dietary components may play a role in the prevention of type
      2 diabetes. OBJECTIVE: We examined prospectively the associations between whole-
      and refined-grain intake and the risk of type 2 diabetes in a large cohort of
      men. DESIGN: Men from the Health Professionals Follow-up Study without a history
      of diabetes or cardiovascular disease in 1986 (n = 42898) were followed for </=12
      y. Intakes of whole and refined grains, measured every 4 y by use of food
      frequency questionnaires, were used to predict subsequent type 2 diabetes risk
      through multivariate analysis. RESULTS: We ascertained 1197 cases of incident
      type 2 diabetes. After adjustment for age; physical activity; cigarette smoking;
      alcohol consumption; family history of diabetes; and fruit, vegetable, and energy
      intakes, the relative risk of type 2 diabetes was 0.58 (95% CI: 0.47, 0.70; P for
      trend < 0.0001) comparing the highest with the lowest quintile of whole-grain
      intake. The association was moderately attenuated when additionally adjusted for
      body mass index (relative risk: 0.70; 95% CI: 0.57, 0.85; P for trend = 0.0006).
      Intake of refined grains was not significantly associated with risk of type 2
      diabetes. After further adjustment for magnesium intake, cereal fiber intake, and
      glycemic load, the association between whole grains and type 2 diabetes was
      attenuated and the trend no longer significant. CONCLUSIONS: In men, a diet high
      in whole grains is associated with a reduced risk of type 2 diabetes in men that
      may be mediated by cereal fiber. Efforts should be made to replace refined-grain
      with whole-grain foods.

PMID- 12197997
TI  - Resting energy expenditure in diabetic and nondiabetic patients with liver
      cirrhosis: relation with insulin sensitivity and effect of liver transplantation
      and immunosuppressive therapy.
AB  - BACKGROUND: Hypermetabolism, insulin resistance, and diabetes are common in
      patients with liver cirrhosis. OBJECTIVE: We assessed whether diabetes and
      insulin resistance influence postabsorptive energy homeostasis in these patients
      and whether liver transplantation (LTx) and immunosuppressive drugs affect these
      relations. DESIGN: Twenty-six patients with liver cirrhosis (16 with and 10
      without diabetes) were studied with an insulin clamp and indirect calorimetry.
      Eleven of these subjects were studied 9 mo after LTx to longitudinally assess its
      effects. To cross-sectionally explore a longer follow-up period, we studied 65
      patients 6, 14, and 32 mo after LTx. Seven patients with chronic uveitis
      (receiving immunosuppressive therapy) and 20 healthy subjects served as control
      subjects. RESULTS: Diabetic and nondiabetic patients with cirrhosis had insulin
      resistance (S(I(clamp)); P < 0.03) and higher measured resting energy expenditure
      (REE) as a percentage of predicted REE than did healthy subjects (107.6 +/- 1.8%
      compared with 97.4 +/- 2.3%; P < 0.03), and these 2 alterations were associated
      (R(2) = 0.119, P = 0.0002). The longitudinal study showed an improvement in the 2
      variables after LTx, but full restoration was not achieved. The cross-sectional
      analysis confirmed this observation in patients studied 6 mo (n = 28) after LTx.
      In patients studied 14 (n = 21) and 32 mo (n = 16) after LTx, S(I(clamp)) and
      measured REE as a percentage of predicted REE were not significantly different
      from those in control subjects. CONCLUSIONS: In patients with liver cirrhosis,
      higher-than-normal postabsorptive REE was associated with insulin resistance
      regardless of diabetes. This abnormality persisted in patients studied 6-9 mo
      after LTx but improved simultaneously with the improvement in insulin sensitivity
      thereafter.

PMID- 12197998
TI  - Effects of vitamin C and vitamin E on in vivo lipid peroxidation: results of a
      randomized controlled trial.
AB  - BACKGROUND: Lipid peroxidation may be important in the pathogenesis of
      atherosclerosis, particularly in its earliest stages. Evidence predominantly from
      in vitro studies suggests that antioxidant vitamins can prevent lipid
      peroxidation and that vitamin C and vitamin E have synergistic effects. However,
      in vivo evidence in support of these hypotheses is sparse. OBJECTIVE: The
      objective was to determine the effects of vitamin C and vitamin E, alone or in
      combination, on in vivo lipid peroxidation. DESIGN: We conducted a placebo
      controlled, 2 x 2 factorial trial of vitamin C (500 mg ascorbate/d) and vitamin E
      (400 IU RRR-alpha-tocopheryl acetate/d) supplementation in 184 nonsmokers. The
      mean duration of supplementation was 2 mo. The outcome measures were changes from
      baseline in urinary 8-iso-prostaglandin F(2alpha), urinary malondialdehyde + 4
      hydroxyalkenals, and serum oxygen-radical absorbance capacity. RESULTS: The
      within-group mean changes (and 95% CIs) in urinary 8-iso-prostaglandin F(2alpha)
      (pg/mg creatinine) were 9.0 (-125.1, 143.1), -150.0 (-275.4, -24.6), -141.3 (
      230.5, -52.1), and -112.5 (-234.8, 9.8) in the placebo, vitamin C alone, vitamin
      E alone, and vitamins C + E groups, respectively. No synergistic effect of these
      2 vitamins on urinary 8-iso-prostaglandin F(2alpha) was observed (P = 0.12).
      Neither vitamin had an effect on urinary malondialdehyde + 4-hydroxyalkenals.
      Vitamin C, but not vitamin E, increased serum oxygen-radical absorbance capacity
      (P = 0.01). CONCLUSIONS: Supplementation with vitamin C or vitamin E alone
      reduced lipid peroxidation to a similar extent. Supplementation with a
      combination of vitamins C and E conferred no benefit beyond that of either
      vitamin alone.

PMID- 12197999
TI  - Zinc absorption from a low-phytic acid maize.
AB  - BACKGROUND: Phytic acid reduction in cereal grains has been accomplished with
      plant genetic techniques. These low-phytic acid grains provide a strategy for
      improving the mineral (eg, zinc) status in populations that are dependent on
      grains, including maize (Zea mays L.), as major dietary staples. OBJECTIVE: The
      objective was to compare the fractional absorption of zinc from polenta prepared
      from maize low in phytic acid with that prepared from a wild-type isohybrid maize
      (control) after short-term consumption by adults whose habitual diet is low in
      phytic acid. DESIGN: Healthy adults served as their own control subjects in a
      crossover design. All meals on 1 d consisted of polenta prepared from a low
      phytic acid maize homozygous for the recessive low phytic acid 1-1 (lpa1-1). On
      the preceding or following day, all meals consisted of polenta prepared from a
      sibling isohybrid homozygous wild-type maize with a "normal" phytic acid content.
      The low-phytic acid maize contained approximately 60% less phytic acid than did
      the wild-type maize. All test meals were extrinsically labeled with zinc stable
      isotope tracers. The fractional absorption of zinc was determined on the basis of
      fecal enrichment. RESULTS: The molar ratios of phytic acid to zinc in the polenta
      prepared from lpa1-1 maize and the wild-type maize were 17:1 and 36:1,
      respectively. The corresponding fractional absorptions of zinc were 0.30 +/- 0.13
      and 0.17 +/- 0.11, respectively (P < 0.005). CONCLUSION: Substitution of a low
      phytic acid grain in a maize-based diet is associated with a substantial increase
      in zinc absorption.

PMID- 12198000
TI  - Flavonoid intake and risk of chronic diseases.
AB  - BACKGROUND: Flavonoids are effective antioxidants and may protect against several
      chronic diseases. OBJECTIVE: The association between flavonoid intake and risk of
      several chronic diseases was studied. DESIGN: The total dietary intakes of 10 054
      men and women during the year preceding the baseline examination were determined
      with a dietary history method. Flavonoid intakes were estimated, mainly on the
      basis of the flavonoid concentrations in Finnish foods. The incident cases of the
      diseases considered were identified from different national public health
      registers. RESULTS: Persons with higher quercetin intakes had lower mortality
      from ischemic heart disease. The relative risk (RR) between the highest and
      lowest quartiles was 0.79 (95% CI: 0.63, 0.99: P for trend = 0.02). The incidence
      of cerebrovascular disease was lower at higher kaempferol (0.70; 0.56, 0.86; P =
      0.003), naringenin (0.79; 0.64, 0.98; P = 0.06), and hesperetin (0.80; 0.64,
      0.99; P = 0.008) intakes. Men with higher quercetin intakes had a lower lung
      cancer incidence (0.42; 0.25, 0.72; P = 0.001), and men with higher myricetin
      intakes had a lower prostate cancer risk (0.43; 0.22, 0.86; P = 0.002). Asthma
      incidence was lower at higher quercetin (0.76; 0.56, 1.01; P = 0.005), naringenin
      (0.69; 0.50, 0.94; P = 0.06), and hesperetin (0.64; 0.46, 0.88; P = 0.03)
      intakes. A trend toward a reduction in risk of type 2 diabetes was associated
      with higher quercetin (0.81; 0.64, 1.02; P = 0.07) and myricetin (0.79; 0.62,
      1.00; P = 0.07) intakes. CONCLUSION: The risk of some chronic diseases may be
      lower at higher dietary flavonoid intakes.

PMID- 12198001
TI  - Independent effects of residual renal function and dialysis adequacy on dietary
      micronutrient intakes in patients receiving continuous ambulatory peritoneal
      dialysis.
AB  - BACKGROUND: Dialysis patients are at risk of vitamin and mineral deficiencies,
      not only because of losses during chronic hemodialysis or peritoneal dialysis but
      also because of low intakes. OBJECTIVE: The objective was to determine the
      importance of urea clearance (calculated as K(t)/V) and residual renal function
      (RRF) in predicting micronutrient intakes in a large cohort of patients receiving
      continuous ambulatory peritoneal dialysis (CAPD). DESIGN: We conducted a survey
      of dietary intakes in 242 CAPD patients and divided them into 3 groups according
      to their weekly urea clearance and RRF: WD group (n = 84), a urea clearance >/=
      1.7 and a glomerular filtration rate (GFR) >/= 1 mL x min(-1) x 1.73 m(-2); DD
      group (n = 71), a urea clearance >/= 1.7 and a GFR < 1 mL x min(-1) x 1.73 m(-2);
      and ID group (n = 87), a urea clearance < 1.7. RESULTS: Most of the patients had
      intakes of water-soluble vitamins and minerals that were lower than the
      recommended dietary allowance; most intakes were significantly higher in the WD
      group than in the DD and ID groups, except those of niacin and calcium. After
      age, sex, body weight, and the presence of diabetes were controlled for, total
      weekly urea clearance and the GFR (but not peritoneal dialysis urea clearance)
      were significantly associated with intakes of vitamins A and C, the B vitamins,
      and minerals (calcium, phosphate, iron, and zinc). Low intakes of vitamins and
      minerals with low RRF and urea clearance were the result of reduced overall food
      intakes, except for thiamine, vitamin B-6, and folic acid, which were deficient
      in the diet. CONCLUSIONS: Supplementation with most water-soluble vitamins and
      minerals, including iron and zinc, should be considered in CAPD patients,
      especially those with low RRF and low urea clearance. The optimal dose needs to
      be determined.

PMID- 12198002
TI  - Iron bis-glycine chelate competes for the nonheme-iron absorption pathway.
AB  - BACKGROUND: The enterocytic absorption pathway of the food fortificant iron bis
      glycine chelate has been the subject of controversy because it is not clear
      whether that substance uses the classic nonheme-iron absorption pathway or a
      pathway similar to that of heme absorption. OBJECTIVE: The objective was to study
      the absorption pathway of iron bis-glycine chelate in human subjects. DESIGN:
      Eighty-five healthy adult women were selected to participate in 1 of 6 iron
      absorption studies. Study A involved the measurement of the dose-response curve
      of the absorption of ferrous sulfate (through a nonheme-iron absorption pathway);
      study B involved the competition of iron bis-glycine chelate with ferrous sulfate
      for the nonheme-iron absorption pathway; study C involved the measurement of the
      dose-response curve of heme-iron absorption; study D involved the competition of
      iron bis-glycine chelate with hemoglobin for the heme-iron absorption pathway;
      and studies E and F were the same as studies A and B, except that the iron bis
      glycine chelate was encapsulated in enteric gelatin capsules so that it would not
      be processed in the stomach. RESULTS: Iron from the bis-glycine chelate competed
      with ferrous sulfate for the nonheme-iron absorption pathway. Iron from the bis
      glycine chelate also competed with ferrous sulfate for absorption when liberated
      directly into the intestinal lumen. Iron from the bis-glycine chelate did not
      compete with heme iron for the heme-iron absorption pathway. CONCLUSION: The iron
      from iron bis-glycine chelate delivered at the level of the stomach or duodenum
      becomes part of the nonheme-iron pool and is absorbed as such.

PMID- 12198003
TI  - Dietary and circulating antioxidant vitamins in relation to carotid plaques in
      middle-aged women.
AB  - BACKGROUND: The results of the few studies conducted on the relation between
      antioxidant vitamins and carotid atherosclerosis have been inconclusive.
      OBJECTIVE: We evaluated the association between preclinical carotid
      atherosclerosis, as determined by high-resolution B-mode ultrasound, and both the
      intake amounts and plasma concentrations of antioxidant vitamins. DESIGN: Among
      5062 participants in Progetto Atena, a population-based study on the etiology of
      cardiovascular disease and cancer in women, 310 women were examined by B-mode
      ultrasound to detect early signs of carotid atherosclerosis. The participants
      answered a food-frequency questionnaire, and their plasma concentrations of
      vitamin E, vitamin A, and carotenoids were measured. None of the women took
      vitamin supplements. RESULTS: The occurrence of atherosclerotic plaques at the
      carotid bifurcation was inversely associated with tertiles of vitamin E intake;
      the test for a linear trend across tertiles was significant (P < 0.05).
      Similarly, the ratio of plasma vitamin E to plasma cholesterol was inversely
      related to the presence of plaques at the carotid bifurcation; the test for a
      linear trend across tertiles was significant (P < 0.02). No association was found
      between the intake of other antioxidant vitamins (vitamins A and C and
      carotenoids) or their plasma concentrations and the presence of carotid plaques.
      CONCLUSIONS: An inverse association was found between both the intake amount and
      plasma concentration of vitamin E and preclinical carotid atherosclerosis in
      middle-aged women. This association was independent of other cardiovascular risk
      factors, was not related to vitamin supplements, and supports the hypothesis that
      low vitamin E intake is a risk factor for early atherosclerosis.

PMID- 12198004
TI  - Pharmacokinetics of the glucuronide and sulfate conjugates of genistein and
      daidzein in men and women after consumption of a soy beverage.
AB  - BACKGROUND: The soy isoflavones genistein and daidzein are found in blood and
      tissues as aglycones, glucuronides, and sulfates. Isoflavone conjugates may serve
      as sources of aglycones at specific target tissues and may have bioactivity. Yet,
      very little is known about the plasma pharmacokinetics of isoflavone conjugates
      after soy ingestion. OBJECTIVE: The objective of this study was to determine the
      plasma pharmacokinetics of glucuronide and sulfate conjugates of genistein and
      daidzein in humans after the consumption of a drink made with soy-protein
      isolate. DESIGN: Six men and 6 women ( +/- SD age: 40.8 +/- 3 y) consumed a soy
      protein-isolate drink. The pharmacokinetics of isoflavone glucuronide and sulfate
      conjugates were studied with the use of beta-glucuronidase (EC 3.2.1.31) and
      sulfatase (EC 3.1.6.1) digestion and liquid chromatography-mass spectrometry.
      RESULTS: Glucuronides of genistein and daidzein made up a significantly lower
      percentage (P < 0.05) of the total isoflavone concentration in plasma (48% and
      33%, respectively) than in urine. The percentages of sulfates of genistein and
      daidzein in plasma (8% and 26%, respectively) were 2- to 6-fold those in urine (P
      < 0.05). Approximately 30% of the total genistein or daidzein was comprised of
      mixed conjugates (one glucuronide and one sulfate). For daidzein sulfate,
      genistein sulfate, daidzein glucuronide, and genistein glucuronide, the time to
      peak (t(max)) was 4.5, 4.5, 4.5, and 6.0 h, respectively, and the apparent half
      life (t(1/2 lambdaz)) was 3.1, 5.7, 3.2, and 8.4 h, respectively. CONCLUSIONS:
      These data suggest that there are significant differences in the pharmacokinetics
      of sulfate and glucuronide conjugates of isoflavones. This may have important
      implications for the meal frequency and maintenance of target tissue bioactivity
      required to elicit potential health benefits.

PMID- 12198005
TI  - Macular pigment density in relation to serum and adipose tissue concentrations of
      lutein and serum concentrations of zeaxanthin.
AB  - BACKGROUND: Macular pigment (MP), concentrated in the central area of the retina,
      contains the carotenoids lutein and zeaxanthin. A low MP density could be a risk
      factor for age-related macular degeneration. Little information is available
      regarding MP density in relation to serum lutein and zeaxanthin and adipose
      lutein concentrations in a general population. OBJECTIVE: The objective was to
      investigate the associations between MP density and serum lutein, serum
      zeaxanthin, and adipose lutein, taking into account potential confounders in a
      population. DESIGN: Volunteers (n = 376) aged 18-75 y were recruited. In a cross
      sectional design, serum (n = 376) and adipose tissue (n = 187) were analyzed for
      carotenoids, and MP density was measured by spectral fundus reflectance. RESULTS:
      Mean MP density in the total study group was 0.33 +/- 0.15. MP density was 13%
      higher in men than in women (P < 0.05). Serum and blood concentrations of alpha
      tocopherol, vitamin C, and all carotenoids except lycopene were significantly
      higher in women. Adipose lutein concentrations were also significantly higher in
      women than in men. Regression models showed a positive significant association
      between MP density and serum lutein, serum zeaxanthin, and adipose lutein
      concentrations in men after adjustment for age, but no relation in women. In men,
      serum lutein remained significantly associated with MP density after adjustment
      for age, total cholesterol, body mass index, and smoking. CONCLUSION: The
      associations between MP density and serum lutein, serum zeaxanthin, and adipose
      lutein concentrations are stronger in men than in women.

PMID- 12198006
TI  - Zinc supplementation as adjunct therapy in children with measles accompanied by
      pneumonia: a double-blind, randomized controlled trial.
AB  - BACKGROUND: Zinc deficiency, common in developing countries, is associated with
      decreased immunocompetence. Zinc supplementation benefits children with acute and
      persistent diarrhea and prevents pneumonia. Most deaths from vaccine-preventable
      diseases are from measles and whooping cough; pneumonia is the most common
      complication of measles and often the proximate cause of related deaths.
      OBJECTIVE: We evaluated the effect of zinc supplementation on episodes of illness
      in children with measles accompanied by pneumonia. DESIGN: In a double-blind,
      randomized controlled trial, children aged 9 mo-15 y who were admitted to the
      Infectious Diseases Hospital in Calcutta with clinically severe measles
      accompanied by pneumonia and who had been ill for </= 7 d were randomly assigned
      to receive zinc (20 mg, in elemental form as acetate, twice daily for 6 d) or a
      placebo. All patients received standard treatment with antibiotics and an initial
      100 000-IU dose of vitamin A (as palmitate) by mouth. RESULTS: Time-to-event
      analysis using the Cox proportional hazards model (42 in the zinc group and 43 in
      the placebo group) showed that the time needed for the resolution of fever and
      tachypnea, the return of appetite, and the achievement of a "much improved" or
      "cured" status was not different between the 2 groups. A high proportion of
      children had low serum retinol and zinc concentrations. Improvement in serum zinc
      and retinol concentrations after 6 d of treatment was not different between the 2
      groups. CONCLUSION: Children with severe measles accompanied by pneumonia treated
      with antibiotics and vitamin A did not show any additional benefit from also
      receiving a zinc supplement.

PMID- 12198007
TI  - Higher maternal plasma docosahexaenoic acid during pregnancy is associated with
      more mature neonatal sleep-state patterning.
AB  - BACKGROUND: The effect of docosahexaenoic acid (DHA) on the developing fetal
      central nervous system (CNS) and related functional outcomes in infancy remain
      unexplored. Sleep and wake states of newborns provide a tool for assessing the
      functional integrity of the CNS. OBJECTIVE: We investigated whether CNS integrity
      in newborns, measured with sleep recordings, was associated with maternal
      concentrations of long-chain polyunsaturated fatty acids, especially DHA. DESIGN:
      Plasma phospholipid fatty acid concentrations were measured in 17 women at
      parturition. On postpartum day 1 (P1) and day 2 (P2), a pressure-sensitive pad
      under the infants' bedding recorded body movements and respiratory patterns to
      measure sleep and wake states. RESULTS: Maternal plasma phospholipid DHA ranged
      from 1.91% to 4.5% by wt of total fatty acids. On the basis of previously
      published data and the median DHA concentration, the women were divided into 2
      groups: high DHA (> 3.0% by wt of total fatty acids) and low DHA (</= 3.0% by wt
      of total fatty acids). Infants of high-DHA mothers had a significantly lower
      ratio of active sleep (AS) to quiet sleep (QS) and less AS than did infants of
      low-DHA mothers. Furthermore, the former infants had less sleep-wake transition
      and more wakefulness on P2. Correlations of maternal DHA status with infant sleep
      states were consistent with these data. Also, the ratio of maternal n-6 to n-3
      fatty acids on P1 was inversely associated with QS and positively associated with
      arousals in QS. On P2, maternal n-6:n-3 was positively associated with AS, sleep
      wake transition, and AS:QS. CONCLUSION: The sleep patterns of infants born to
      mothers with higher plasma phospholipid DHA suggest greater CNS maturity.

PMID- 12198008
TI  - The pregnancy-related decrease in fasting plasma homocysteine is not explained by
      folic acid supplementation, hemodilution, or a decrease in albumin in a
      longitudinal study.
AB  - BACKGROUND: Fasting plasma total homocysteine (tHcy) decreases during pregnancy.
      Previous reports suggested that this is due to folic acid supplementation,
      hemodilution, or a decrease in albumin. However, these hypotheses have not been
      tested in a longitudinal study. OBJECTIVE: We investigated the relation between
      pregnancy-related physiologic changes and tHcy in a group of healthy women who
      were either unsupplemented or supplemented with folic acid. DESIGN: In a
      longitudinal study from preconception throughout pregnancy, we studied 54
      unsupplemented women and 39 women who were supplemented with folic acid during
      the second or third trimester of pregnancy. tHcy, hematocrit, and serum albumin
      were determined preconceptionally and at 8, 20, and 32 wk of pregnancy. RESULTS:
      For the entire group, geometric mean tHcy concentrations at preconception (8.2
      micro mol/L) were significantly greater (P < 0.001) than those at 8 wk of
      pregnancy (6.4 micro mol/L). When the unsupplemented and supplemented groups were
      regarded separately, geometric mean tHcy concentrations at preconception were
      significantly greater than those at 20 (5.22 and 4.18 micro mol/L, respectively)
      and 32 (5.16 and 4.42 micro mol/L, respectively) wk of pregnancy (P < 0.001 for
      both). Mean reductions from preconception concentrations at 8, 20, and 32 wk of
      pregnancy were significantly greater (P < 0.001) for tHcy (-11.5%, -25.5%, and 
      24.5%, respectively) than for hematocrit (-1.9%, -4.2%, and -4.3%, respectively)
      or serum albumin (-1.1%, -9.8%, and -13.4%, respectively). There was no
      correlation between changes in either hematocrit or serum albumin and changes in
      tHcy. CONCLUSIONS: This study refutes the previous explanations for the reduction
      in plasma tHcy known to occur in pregnancy, namely, folic acid supplementation,
      hemodilution, and a decrease in serum albumin. We suggest that the changes may be
      endocrine-based.

PMID- 12198009
TI  - Growth of healthy infants and the timing, type, and frequency of complementary
      foods.
AB  - BACKGROUND: Growth patterns of exclusively and predominantly breast-fed infants
      differ from those of non-breast-fed infants, but less is known about associations
      among growth patterns and different durations of exclusive breast-feeding and the
      types and frequency of complementary foods. OBJECTIVE: We examined these
      associations, particularly between 4 and 6 mo of age, using data from a unique
      longitudinal 7-country study. DESIGN: Data from the World Health Organization
      Multinational Study of Breast-feeding and Lactational Amenorrhea on infants
      living in generally favorable environments were used. Multilevel analyses
      described growth and the relation between growth and variables related to
      feeding. RESULTS: Small differences in growth that were statistically significant
      but probably not biologically important were noted among infants in whom
      complementary foods were introduced at different times. Weight gain was more
      sensitive to feeding frequencies than were gains in length, but the cumulative 10
      wk differences were small. The most extreme differences were equivalent to
      approximately 10 centiles of the weight and height distributions at 6 mo of age.
      CONCLUSIONS: These results do not provide compelling evidence of benefit or risk
      related to growth and the timing of introduction of complementary foods at any
      specific time between 4 and 6 mo of age. Thus, postnatal growth appears to not be
      sensitive to the differential timing of introduction of complementary foods nor
      to differential types and frequencies of complementary foods in healthy infants
      living in environments without major economic constraints and low rates of
      illness. These results, however, may not indicate growth differences in
      populations living in poor environments.

PMID- 12198010
TI  - Anthropometric assessment of muscularity during growth: estimating fat-free mass
      with 2 skinfold-thickness measurements is superior to measuring midupper arm
      muscle area in healthy prepubertal children.
AB  - BACKGROUND: Anthropometric measurements are widely used to determine body
      composition, especially in children. OBJECTIVE: Our aim was to compare 2 of the
      simplest anthropometry-based equations available for determining nutritional
      status and muscularity in children and adolescents, examined in relation to other
      methodologically independent muscle variables. DESIGN: Midupper arm muscle area
      (UAMA) and fat-free mass (FFM) according to the equations of Slaughter et al (Hum
      Biol 1988;60:709-23), as well as separate biochemical, physical, and radiologic
      muscle variables, were determined cross-sectionally in 91 males and 91 females
      aged 6-18 y. The ability of UAMA and FFM to estimate muscularity, as measured by
      24-h creatinine excretion, grip force, and peripheral quantitative computer
      tomography analysis of forearm muscle, was compared after dividing the study
      population into prepubertal and pubertal groups. RESULTS: Before puberty,
      correlations of all 3 muscularity variables were higher with FFM than with UAMA
      in both males and females. Multiple regression analyses confirmed FFM to be the
      predominant predictor, with partial R(2) >/= 0.68 (P < 0.001). However, in
      puberty, FFM did not consistently show this major influence. Only before puberty
      did FFM provide a significantly better fit (P < 0.05) than did UAMA for 2 of the
      3 muscularity variables in each sex. CONCLUSIONS: The FFM estimate proved to be
      the better predictor for muscularity in healthy prepubertal children and is on a
      par with UAMA during puberty. FFM can be recommended as a simple anthropometric
      method to assess nutritional status before puberty, at least in healthy children.

PMID- 12198011
TI  - Response of splanchnic and whole-body leucine kinetics to treatment of children
      with edematous protein-energy malnutrition accompanied by infection.
AB  - BACKGROUND: Although the reduction in whole-body protein turnover and net protein
      loss induced by protein-energy malnutrition (PEM) has been well documented, it is
      unclear whether the protein-sparing mechanisms elicited by chronically inadequate
      intakes of dietary protein and energy are affected by the protein catabolic
      response to infection. OBJECTIVE: The objective of this study was to determine
      whether the presence of infection alters the PEM-induced reduction in whole-body
      protein metabolism. DESIGN: We determined whole-body leucine kinetics in 4 boys
      and 3 girls aged 6-15 mo with edematous PEM and infection approximately 3 d after
      admission (study 1), when they were both infected and malnourished; approximately
      11 d after admission (study 2), when infection had resolved but they were still
      anthropometrically malnourished; and at recovery (study 3), when weight-for
      length was at least 90% of that expected. RESULTS: The children had significantly
      less leucine flux in both study 1 and study 2 than they had in study 3. There
      were no significant differences in the amount of leucine released from protein
      breakdown or used for protein synthesis between study 1 and study 2. There were
      no significant differences in leucine balance or in either the amount or
      percentage of enteral leucine extracted by the splanchnic tissues among the 3
      studies. CONCLUSIONS: When subjects are in the fed state, severe PEM induces a
      marked reduction in whole-body protein synthesis and breakdown rates, and the
      presence of infection does not alter this adaptation and hence the overall
      protein balance. A corollary is that children with severe PEM do not mount a
      protein catabolic response to infection.

PMID- 12198012
TI  - Age and copper intake do not affect copper absorption, measured with the use of
      65Cu as a tracer, in young infants.
AB  - BACKGROUND: Copper homeostasis involves a high degree of regulation in which
      changes in absorption and biliary excretion are the main mechanisms. Whether
      neonates and small infants can make these changes efficiently is unknown.
      OBJECTIVE: We evaluated the effect of age and copper intake on copper absorption
      in infants during the first 3 mo of life. DESIGN: Thirty-nine healthy infants (19
      infants aged 1 mo and 20 infants aged 3 mo) were selected. One-half of the
      subjects were randomly assigned to receive oral supplementation of 80 mg Cu (as
      copper sulfate). kg body wt(-1). d(-1) for 15 d. At the end of the trial, copper
      absorption was measured by using orally administered (65)Cu as a tracer and fecal
      monitoring of recovered (65)Cu. RESULTS: Mean (+/- SD) copper absorption at 1 mo
      of age was 83.6 +/- 5.8% and 74.8 +/- 9.1% for the unsupplemented and
      supplemented infants, respectively. The corresponding figures at 3 mo of age were
      77.6 +/- 15.2% and 77.7 +/- 11.3%. A two-way analysis of variance showed that
      age, copper supplementation, and the interaction between age and copper
      supplementation did not have a significant effect on copper absorption. There was
      an inverse correlation between total fecal copper and the percentage of (65)Cu
      absorption (r = -0.50, P < 0.003). CONCLUSION: Copper absorption in young infants
      is high but does not respond to copper intake within the range tested.

PMID- 12198013
TI  - Cysteine supplementation improves the erythrocyte glutathione synthesis rate in
      children with severe edematous malnutrition.
AB  - BACKGROUND: Children with severe edematous malnutrition have higher than normal
      oxidant damage and lower concentrations of the antioxidant reduced glutathione
      (GSH), which are associated with slower synthesis of GSH and with low extra- and
      intracellular concentrations of the precursor amino acid cysteine. OBJECTIVE: We
      tested whether early dietary supplementation with cysteine could restore a normal
      GSH concentration and synthesis rate in these children. DESIGN: Erythrocyte
      cysteine and GSH concentrations and the fractional and absolute synthesis rates
      of GSH were measured in 2 groups of 16 edematous malnourished children, 10 boys
      and 6 girls aged 6-18 mo, at 3 times after hospital admission: at approximately 2
      d (period 1), when they were malnourished and infected; at approximately 11 d
      (period 2), when they were malnourished but cleared of infection; and at
      approximately 50 d (period 3), when they had recovered. Supplementation with
      either 0.5 mmol. kg(-1). d(-1) N-acetylcysteine (NAC group) or alanine (control
      group) started immediately after period 1 and continued until recovery. RESULTS:
      From period 1 to period 2 the concentration and the absolute synthesis rate of
      GSH increased significantly (P < 0.05) in the NAC group but not in the control
      group. The increases in the GSH concentration and synthesis rate were
      approximately 150% and 510% greater, respectively, in the NAC group than in the
      control group. The increases in the NAC group were associated with a significant
      effect of supplement (P < 0.03) on erythrocyte cysteine concentration.
      CONCLUSION: These results suggest that the GSH synthesis rate and concentration
      can be restored during the early phase of treatment if patients are supplemented
      with cysteine.

PMID- 12198014
TI  - Predicting overweight and obesity in adulthood from body mass index values in
      childhood and adolescence.
AB  - BACKGROUND: The Centers for Disease Control and Prevention (CDC) introduced the
      clinical use of the body mass index (BMI; in kg/m(2)) in growth charts for young
      males and females. OBJECTIVE: This study updates our previous report with the use
      of new CDC BMI charts and definitions of adult overweight and obesity to predict
      adult overweight or obesity. DESIGN: Logistic models were fitted to relate adult
      overweight and obesity to childhood and adolescent BMI values at each age for 166
      males and 181 females in the Fels Longitudinal Study and were applied to predict
      adult overweight and obesity at the 75th, 85th, and 95th percentiles on the CDC
      charts of childhood and adolescent BMI. RESULTS: A child or adolescent with a
      high BMI percentile on the CDC BMI-for-age growth charts has a high risk of being
      overweight or obese at 35 y of age, and this risk increases with age. For
      example, the probability of adult obesity at the 85th percentile for young males
      was </=20% to 17 y of age and 20-59.9% afterward; the corresponding probability
      for young females was 20-39.9% to 18 y of age and 40-59.9% afterward. CONCLUSION:
      Our clinically applicable method assigns a child's or adolescent's BMI value to a
      group with a known probability of overweight or obesity in adulthood.

PMID- 12198015
TI  - Plasma cholecystokinin is associated with subjective measures of satiety in
      women.
AB  - BACKGROUND: Cholecystokinin is associated with satiety. Fat stimulates
      cholecystokinin release, and fiber appears to prolong cholecystokinin elevation
      during the alimentary period. OBJECTIVE: We tested whether adding fiber or fat to
      a low-fat, low-fiber meal increases cholecystokinin release and enhances
      subjective measures of satiety and whether the cholecystokinin response
      correlates with subjective measures of satiety. DESIGN: Three isoenergetic
      breakfast meals were tested in a randomized crossover design: low fiber, low fat;
      high fiber, low fat; and low fiber, high fat. Blood samples were drawn from
      fasted subjects (7 men and 8 women) before and at different time points after
      test meal consumption for 6 h. Plasma was analyzed for cholecystokinin, insulin,
      glucose, and triacylglycerols. Visual analogue scales were used to assess
      subjects' hunger, desire to eat, fullness, and prospective consumption. RESULTS:
      In the women, the meals higher in fiber or in fat resulted in greater feelings of
      satiety and in significantly higher cholecystokinin responses than did the low
      fat, low-fiber meal. In the men, the increase in cholecystokinin concentration
      did not differ between meals, but the 2 low-fat meals elicited a greater feeling
      of satiety than did the high-fat meal. The insulin response was significantly
      higher for the low-fiber, low-fat meal than for the other 2 meals, and the
      triacylglycerol response was greatest for the high-fat, low-fiber meal.
      CONCLUSION: In women, the feeling of satiety caused by cholecystokinin release is
      enhanced by increasing either the fiber or fat content of a low-fat, low-fiber
      meal.

PMID- 12198016
TI  - Generation of protein adducts with malondialdehyde and acetaldehyde in muscles
      with predominantly type I or type II fibers in rats exposed to ethanol and the
      acetaldehyde dehydrogenase inhibitor cyanamide.
AB  - BACKGROUND: Alcoholic myopathy is known to primarily affect type II muscle fibers
      (glycolytic, fast-twitch, anaerobic), whereas type I fibers (oxidative, slow
      twitch, aerobic) are relatively protected. OBJECTIVE: We investigated whether
      aldehyde-derived adducts of proteins with malondialdehyde and acetaldehyde are
      formed in muscle of rats as a result of acute exposure to ethanol and
      acetaldehyde. The differences between type I muscle, type II muscle, and liver
      tissue were also assessed. DESIGN: The formation and distribution of
      malondialdehyde- and acetaldehyde-protein adducts were studied with
      immunohistochemistry in soleus (type I) muscle, plantaris (type II) muscle, and
      liver in 4 groups of rats. The different groups were administered saline
      (control), cyanamide (an acetaldehyde dehydrogenase inhibitor), ethanol, and
      cyanamide + ethanol. RESULTS: Treatment of rats with ethanol and cyanamide +
      ethanol increased the amount of aldehyde-derived protein adducts in both soleus
      and plantaris muscle. The greatest responses in malondialdehyde-protein and
      acetaldehyde-protein adducts were observed in plantaris muscle, in which the
      effect of alcohol was further potentiated by cyanamide pretreatment.
      Malondialdehyde- and acetaldehyde-protein adducts were also found in liver
      specimens from rats treated with ethanol and ethanol + cyanamide; the most
      abundant amounts were found in rats given cyanamide pretreatment. CONCLUSIONS:
      Acute ethanol administration increases protein adducts with malondialdehyde and
      acetaldehyde, primarily in type II muscle. This may be associated with the
      increased susceptibility of anaerobic muscle to alcohol toxicity. Higher
      acetaldehyde concentrations exacerbate adduct formation, especially in type II
      predominant muscles. The present findings are relevant to studies on the
      pathogenesis of alcohol-induced myopathy.

PMID- 12198017
TI  - Children who avoid drinking cow milk have low dietary calcium intakes and poor
      bone health.
AB  - BACKGROUND: Information concerning the adequacy of bone mineralization in
      children who customarily avoid drinking cow milk is sparse. OBJECTIVE: The
      objective was to evaluate dietary calcium intakes, anthropometric measures, and
      bone health in prepubertal children with a history of long-term milk avoidance.
      DESIGN: We recruited 50 milk avoiders (30 girls, 20 boys) aged 3-10 y by
      advertisement. We measured current dietary calcium intakes with a food-frequency
      questionnaire and body composition and bone mineral density with dual-energy X
      ray absorptiometry and compared the results with those of 200 milk-drinking
      control children. RESULTS: The reasons for milk avoidance were intolerance (40%),
      bad taste (42%), and lifestyle choice (18%). Dietary calcium intakes were low
      (443 +/- 230 mg Ca/d), and few children consumed substitute calcium-rich drinks
      or mineral supplements. Although 9 children (18%) were obese, the milk avoiders
      were shorter (P < 0.01), had smaller skeletons (P < 0.01), had a lower total-body
      bone mineral content (P < 0.01), and had lower z scores (P < 0.05) for areal bone
      mineral density at the femoral neck, hip trochanter, lumbar spine, ultradistal
      radius, and 33% radius than did control children of the same age and sex from the
      same community. The z scores for volumetric (size-adjusted) bone mineral density
      (g/cm(3)) were -0.72 +/- 1.17 for the lumbar spine and -0.72 +/- 1.35 for the 33%
      radius (P < 0.001). Twelve children (24%) had previously broken bones.
      CONCLUSIONS: In growing children, long-term avoidance of cow milk is associated
      with small stature and poor bone health. This is a major concern that warrants
      further study.

PMID- 12198018
TI  - Bone mineral contents and plasma osteocalcin concentrations of Gambian children
      12 and 24 mo after the withdrawal of a calcium supplement.
AB  - BACKGROUND: Our randomized, placebo-controlled supplementation study of 160 rural
      Gambian children aged 8.3-11.9 y showed that an increase in calcium intake of 714
      mg/d for 12 mo resulted in a 5% increase in forearm bone mineral acquisition and
      a 22% decrease in plasma osteocalcin concentration, a bone formation marker, but
      had no effect on height or bone dimensions. OBJECTIVE: We investigated whether
      these results were sustained after supplement withdrawal. DESIGN: All
      participants were followed up 12 (FU1) and 24 (FU2) mo after supplementation
      ended. Bone mineral content (BMC), bone mineral density (BMD), and BMC adjusted
      for bone width, body weight, and height (size-adjusted BMC) were measured at the
      midshaft and distal radius. Plasma osteocalcin concentration was measured at FU1.
      RESULTS: At follow-up, the calcium group had greater bone mineral status than did
      the placebo group at the midshaft radius (mean difference +/- SE), FU1: BMC (4.7
      +/- 1.6%; P = 0.004), BMD (5.1 +/- 1.1%; P </= 0.0001), size-adjusted BMC (5.0 +/
      1.1%; P </= 0.0001); FU2: BMC (3.8 +/- 1.6%; P = 0.02), BMD (2.7 +/- 1.3%; P =
      0.04), size-adjusted BMC (2.5 +/- 1.3%; P = 0.06). Similar differentials were
      observed at the distal radius but were not significant. No significant
      differences in plasma osteocalcin concentrations (FU1: -0.5 +/- 6.5%; P = 0.9)
      were observed between groups. CONCLUSION: Although some of the effects of calcium
      supplementation were still evident at follow-up, further studies are required to
      determine whether short-term increases in calcium intake have lasting benefits
      for Gambian children.

PMID- 12198019
TI  - Extra dietary copper inhibits LDL oxidation.

PMID- 12198020
TI  - Dietary treatment of iron deficiency?

PMID- 12198022
TI  - Population estimates of folate intake from food analyses.

PMID- 12198024
TI  - Lessons learned in iron intervention trials.

PMID- 12198026
TI  - Anesthetic-induced immobility: neuronal nicotinic acetylcholine receptors are no
      longer in the picture.

PMID- 12198027
TI  - Low utility of dobutamine stress echocardiograms in the preoperative evaluation
      of patients scheduled for noncardiac surgery.
AB  - In this study, we examined the utility of preoperative dobutamine stress
      echocardiograms (DSE) obtained for 85 patients in accordance with guidelines
      published by the American College of Cardiology (ACC) and the American Heart
      Association (AHA). The medical record of each patient was reviewed to identify
      the clinical criteria that indicated the need for a DSE, the DSE results,
      therapeutic interventions rendered as a result of the DSE, and any perioperative
      cardiac morbidity. The DSE was positive for inducible ischemia in 4 patients
      (4.7%), negative in 74 (87.1%), and nondiagnostic in 7 (8.2%). DSEs that were
      obtained for 48 patients because of a history of diabetes mellitus, mild angina,
      or "minor clinical predictors" produced only negative results. Of the four
      patients with positive DSE results, three underwent coronary angiography, and one
      of those three underwent bypass grafting before surgery. An additional 29
      patients received a preoperative DSE but were excluded from the study because the
      criteria for ordering the DSE did not meet the ACC/AHA guidelines. No patient had
      any perioperative morbidity related to myocardial ischemia. The total patient
      charge for the 85 DSEs obtained at our institution was US$104,635. Use of the
      ACC/AHA guidelines for preoperative DSEs does not appear to be cost-effective.
      However, the current algorithm could be significantly improved by altering the
      criteria for obtaining preoperative DSEs. IMPLICATIONS: This study was a
      retrospective review of 85 patient charts that found a low cost-effectiveness of
      using American College of Cardiology/American Heart Association guidelines for
      obtaining preoperative dobutamine stress echocardiograms. Suggested modifications
      of these guidelines should improve their specificity with no loss in sensitivity.

PMID- 12198028
TI  - Is there a long-term predictive value of intraoperative low-dose dobutamine
      echocardiography in patients who have coronary artery bypass graft surgery with
      cardiopulmonary bypass?
AB  - In patients with coronary artery disease, chronic regional left ventricular
      systolic dysfunction at rest may be caused by hibernating or by infarcted
      myocardium. Intraoperative low-dose dobutamine (LDD) echocardiography reliably
      predicts the immediate recovery of regional myocardial function after coronary
      artery bypass graft (CABG) surgery. We sought to determine whether intraoperative
      LDD echocardiography would also predict recovery of regional function after 1 yr.
      Twenty-five patients with coronary artery disease who underwent CABG surgery with
      intraoperative LDD echocardiography were evaluated 1 yr later with a follow-up
      transthoracic echocardiogram. The covariates of left ventricular ejection
      fraction, old myocardial infarction, and diabetes mellitus were considered in an
      analysis of regional wall motion (RWM). A 16-segment model and a 1-5-point
      scoring system were used to evaluate 350 myocardial segments. Multiple logistic
      regression analysis was performed to determine whether response to intraoperative
      LDD echocardiography (5 microg. kg(-1). min(-1)) predicted changes in regional
      function at 1 yr. A segment was defined as stunned if the RWM score obtained
      during LDD infusion deteriorated after cardiopulmonary bypass but recovered in
      the 1-yr follow-up echocardiogram. A response to intraoperative LDD predicted
      changes in regional function at 1 yr. The overall odds of improvement in regional
      function were 2.22 times greater (95% confidence interval = 1.29, 3.82; P =
      0.0039) with a positive response to intraoperative LDD. The positive predictive
      value of intraoperative LDD echocardiography for improvement in myocardial
      function was 0.81 and the negative predictive value was 0.34. The predictive
      values did not vary with the examined covariates. Of segments with unexpected
      deterioration of RWM immediately after cardiopulmonary bypass, 87% recovered at
      the time of the 1-yr follow-up echocardiogram. Contractile reserve demonstrated
      by intraoperative LDD echocardiography predicts regional function at 1 yr;
      however, the test cannot predict which segment will not recover. Most of
      unexpected regional ventricular systolic dysfunction immediately after CABG
      surgery can be attributed to myocardial stunning. IMPLICATIONS: In patients
      undergoing coronary artery bypass graft surgery, intraoperative low-dose
      dobutamine echocardiography has only limited value for the prediction of regional
      myocardial function at 1 yr. Small-dose dobutamine echocardiography predicts
      regional myocardial function at 1 yr when baseline regional wall motion
      abnormalities improve with dobutamine; however, the test cannot be used to
      predict which segment will not recover at 1 yr.

PMID- 12198029
TI  - Mitral flow propagation velocity identifies patients with abnormal diastolic
      function during coronary artery bypass graft surgery.
AB  - Flow propagation velocity (Vp) is a new method of assessing left ventricular (LV)
      diastolic (D) function that seems to be insensitive to heart rate and preload
      changes. We hypothesized that Vp <50 cm/s identifies patients with D dysfunction
      and that Vp provides an assessment of D function when standard Doppler techniques
      are uninterpretable. We conducted a prospective Doppler echocardiographic
      assessment of D function in 63 patients undergoing coronary artery bypass graft
      surgery. Doppler derivatives of mitral inflow and pulmonary vein flow profiles as
      well as isovolumic relaxation time were compared with Vp before and after
      cardiopulmonary bypass. A Valsalva maneuver was used to decrease preload. All
      patients with D dysfunction had Vp <50 cm/s. A Valsalva maneuver did not affect
      Vp. Vp remained a reliable measure of LV D function when mitral flow profiles
      could not be determined because of changes in heart rate and rhythm. LV filling
      patterns did not change significantly after cardiopulmonary bypass. We conclude
      that Vp is a simple measure of D function during coronary artery bypass graft
      surgery that correlates with standard, load-dependent Doppler echocardiographic
      techniques to identify D dysfunction. Vp <50 cm/s identifies abnormal D function
      in this patient population. IMPLICATIONS: Mitral propagation velocity (Vp) is a
      simple, reproducible measure of diastolic function during coronary artery bypass
      graft surgery that correlates with standard Doppler echocardiographic techniques
      to identify dysfunction in the setting of a rapid heart rate or variable preload.
      Vp <50 cm/s identifies abnormal diastolic function in this patient population.

PMID- 12198030
TI  - Ketamine attenuates neutrophil activation after cardiopulmonary bypass.
AB  - Surgery is associated with activation of neutrophils and their influx into
      affected tissue. The pathogenic role of superoxide production generated by
      activated neutrophils has been documented repeatedly. Ketamine suppresses
      neutrophil oxygen radical production in vitro. In the present study, we compared
      the effect of adding small-dose ketamine to opioids during the induction of
      general anesthesia on superoxide production by neutrophils after coronary artery
      bypass grafting (CABG). Thirty-five patients undergoing elective CABG were
      randomized to one of two groups and prospectively studied in a double-blinded
      manner. The patients received either ketamine 0.25 mg/kg or a similar volume of
      saline in addition to large-dose fentanyl anesthesia. Blood samples were drawn
      before the operation, immediately after cardiopulmonary bypass, 24 and 48
      postoperative h, and on postoperative Days 3-6. Functional capacity of
      neutrophils was assessed by superoxide generation after stimulation with phorbol
      12-myristate 13-acetate, opsonized zymosan, or formyl-methionyl-leucyl
      phenylalanine. The addition of small-dose ketamine to general anesthesia
      attenuates increased production of the superoxide anion (O2-) by neutrophils
      without chemical stimulation and after stimulation with phorbol 12-myristate 13
      acetate, formyl-methionyl-leucyl-phenylalanine, and opsonized zymosan for 4-6
      days after CABG. In addition, ketamine attenuated the percentage of neutrophils
      on postoperative Days 2-6. In the Control group, superoxide production
      significantly increased compared with the baseline value. By contrast, in the
      Ketamine group, this difference was not significant. IMPLICATIONS: In a
      randomized, double-blinded, prospective clinical study, we compared the effect of
      adding small-dose ketamine to opioids during general anesthesia on superoxide
      production and showed that ketamine suppressed the increase of superoxide anion
      production by neutrophils after coronary artery bypass grafting.

PMID- 12198031
TI  - The incidence and outcome of ventricular arrhythmias after noncardiac thoracic
      surgery.
AB  - Atrial arrhythmias are common after thoracic surgery, but the incidence and
      significance of ventricular arrhythmias early after such surgery are not well
      established. Our goal was to determine the incidence and outcome of this
      complication from a continuing prospective database in 412 patients who had
      lobectomy (n = 243) or pneumonectomy (n = 169) and were continuously monitored
      with Holter recorders for 72-96 h postoperatively. The primary end point of the
      study was the occurrence of ventricular tachycardia (VT) defined as three or more
      consecutive wide complexes. Sixty-one of 412 patients (15%) developed 1 or more
      episode of VT. There were no episodes of sustained (>30 s) VT and no patient
      required treatment for hemodynamic compromise associated with any VT episode.
      Patients with VT had a more frequent incidence of a preoperative left bundle
      branch block (P = 0.01) but did not differ in other clinical characteristics,
      operative data, or core temperature on arrival to the postanesthesia care unit,
      when compared with those without VT. Patients who developed VT had significantly
      more atrial premature contractions (P < 0.001), ventricular premature
      contractions (P < 0.001), ventricular couplets (P < 0.001), and postoperative
      atrial fibrillation, 21 of 61 (34%) versus 58 of 351 (17%), P = 0.001, than those
      without VT, respectively. Multivariate logistic regression analysis revealed that
      only postoperative atrial fibrillation occurrence was independently associated
      with VT (relative risk 2.6, 95% confidence intervals 1.4 to 4.8, P = 0.002). We
      conclude that nonsustained VT after noncardiac thoracic surgery occurs frequently
      but is not associated with poor outcome. The strong association of atrial and
      ventricular arrhythmogenesis with VT suggests that vagal withdrawal and/or
      adrenergic hyperactivity may have a role in precipitating these events in the
      early postoperative period. IMPLICATIONS: In 412 patients, we determined that the
      incidence of nonsustained ventricular tachycardia after major thoracic surgery is
      15% and is not associated with poor outcome.

PMID- 12198032
TI  - The pharmacokinetics and tolerability of an intravenous infusion of the new
      hydroxyethyl starch 130/0.4 (6%, 500 mL) in mild-to-severe renal impairment.
AB  - Hydroxyethyl starches (HES) are almost exclusively excreted glomerularly, in part
      after hydrolysis by amylase. HES 130/0.4 (Voluven; Fresenius Kabi Deutschland
      GmbH, Bad Homburg, Germany) was developed to improve pharmacokinetics whereas
      preserving the efficacy of volume effect. We studied the dependency of
      pharmacokinetics of HES 130/0.4 on renal function. Nineteen volunteers with
      stable, non-anuric renal dysfunction, ranging from almost normal creatinine
      clearance (CL(cr)) to severe renal impairment (mean CL(cr): 50.6 mL. min(-1).
      1.73 m(-2)), were given a single infusion of 500 mL 6% HES 130/0.4 over 30 min.
      HES plasma concentrations were determined until 72 h, urinary excretion until 72
      96 h. CL(cr) had been obtained at least twice before and twice after dosing.
      Standard pharmacokinetic calculations and regression analysis were performed.
      Area under the time concentration curve (AUC(0-inf)) clearly depended on renal
      function comparing subjects with CL(cr) < 50 with those with CL(cr) > or =50
      (ratio 1.73). Peak concentration (C(max), 4.34 mg/mL) as well as terminal half
      life (16.1 h, model independent) were not affected by renal impairment. At CL(cr)
      > or =30, 59% of the drug could be retrieved in urine, versus 51% at CL(cr) 15
      <30. The mean molecular weight of HES in plasma was 62,704 d at 30 min, showing
      lower values with increased renal impairment (P = 0.04). Pre-dose amylase
      concentrations inversely correlated with baseline CL(cr). Residual HES plasma
      concentrations after 24 h were small in all subjects (< or =0.6 mg/mL). We
      conclude that HES 130/0.4 (500 mL 6%) can be safely administered to patients even
      with severe renal impairment, as long as urine flow is preserved, without plasma
      accumulation. IMPLICATIONS: Dependency of the pharmacokinetics of hydroxyethyl
      starch 130/0.4 on renal function was studied. The area under the time
      concentration curve increased moderately with more severe renal dysfunction;
      however, small plasma concentrations were observed after 24 h. Terminal half-life
      and peak concentration remained unaffected by renal impairment.

PMID- 12198033
TI  - Thoracic cavity irrigation: an unusual cause of acute ST segment increase.
AB  - IMPLICATIONS: We describe an unusual case of acute ST segment increase secondary
      to warm saline thoracic cavity irrigation during thoracotomy. Temperature
      mediated alteration of myocyte repolarization should be considered in addition to
      myocardial ischemia when ST segment changes occur.

PMID- 12198034
TI  - Anesthesia for a patient with catecholaminergic polymorphic ventricular
      tachycardia.
AB  - IMPLICATIONS: A patient with catecholaminergic polymorphic ventricular
      tachycardia required anesthesia for implantation of a defibrillator. The
      diagnostic criteria, treatment, and anesthetic considerations for this rare,
      familial dysrhythmia are described.

PMID- 12198035
TI  - Airway obstruction associated with transesophageal echocardiography in a patient
      with a giant aortic pseudoaneurysm.
AB  - IMPLICATIONS: Airway compression from insertion of a transesophageal
      echocardiography (TEE) probe has been mostly limited to pediatric patients. We
      present a case of TEE-associated airway obstruction in an adult patient
      undergoing surgery for repair of a giant ascending aortic pseudoaneurysm.

PMID- 12198036
TI  - Insertion of the transesophageal echocardiography probe via endoscopy mask.
AB  - IMPLICATIONS: Transesophageal echocardiography (TEE) has not been used during
      airway manipulation to assess the occasional occurrence of hemodynamic
      instability that occurs especially in cardiac patients. We describe a new
      technique using an endoscopy mask to perform TEE monitoring during airway
      manipulation with a large concentration of supplemented oxygen.

PMID- 12198037
TI  - A subclavian artery injury, secondary to internal jugular vein cannulation, is a
      predictable right-sided phenomenon.
AB  - IMPLICATIONS: Internal jugular vein cannulation is a frequently performed
      procedure. We present a case with a review of the literatures of subclavian
      artery injury secondary to this procedure, recognizing that this complication may
      be a right-sided phenomenon secondary to its unique anatomical layout.

PMID- 12198038
TI  - Left atrial compression by a pericardial hematoma presenting as an obstructing
      intracavitary mass: a difficult differential diagnosis.
AB  - IMPLICATIONS: The differential diagnosis of extracavitary, intramural and
      intracavitary disease may be difficult. An extrinsic compression of the left
      atrium by a dissecting pericardial hematoma was misdiagnosed as an intracavitary
      mass, by echocadiography and computer tomography. This case emphasizes the
      importance of patient history and clinical setting.

PMID- 12198039
TI  - Contralateral tension pneumothorax during one-lung ventilation for lobectomy:
      diagnosis aided by fiberoptic bronchoscopy.
AB  - IMPLICATIONS: Tension pneumothorax during one-lung ventilation can be a life
      threatening emergency. Clinical diagnosis may be confusing in the operative
      setting. We present a case in which fiberoptic bronchoscopy excluded tube
      malpositioning and lead us to the diagnosis of a tension pneumothorax.

PMID- 12198040
TI  - Nonhalogenated anesthetic alkanes and perhalogenated nonimmobilizing alkanes
      inhibit alpha(4)beta(2) neuronal nicotinic acetylcholine receptors.
AB  - The nonhalogenated anesthetic alkanes, cyclopropane and butane, do not enhance
      gamma-aminobutyric acid-elicited GABAergic currents, suggesting that these agents
      produce anesthesia via interactions with other molecular targets. Perhalogenated
      nonimmobilizing alkanes, such as 1,2-dichlorohexafluorocyclobutane and 2,3
      dichlorooctafluorobutane, also fail to enhance GABAergic currents, but display
      specific behavioral effects that are distinct from those of structurally similar
      anesthetics. At concentrations predicted to be anesthetic, 1,2
      dichlorohexafluorocyclobutane and 2,3-dichlorooctafluorobutane produce amnesia
      but fail to produce immobility. Neuronal nicotinic acetylcholine (nACh) receptors
      are sensitive to many anesthetics and are thought to have an important role in
      learning and memory. We postulated that neuronal nACh receptors might mediate the
      common amnestic action of nonhalogenated and perhalogenated alkanes. To test the
      hypothesis that neuronal nACh receptors have a role in mediating the behavioral
      effects of general anesthetics and nonimmobilizers, we quantified the inhibitory
      potencies of nonhalogenated anesthetic alkanes and perhalogenated nonimmobilizing
      alkanes on currents mediated by alpha(4)beta(2) neuronal nACh receptors. Our
      studies reveal that anesthetics and nonimmobilizers significantly inhibit
      alpha(4)beta(2) neuronal nACh receptors at concentrations that suppress learning
      and with potencies that correlate with their hydrophobicities. These results
      support the hypothesis that alpha(4)beta(2) neuronal nACh receptors mediate the
      amnestic actions of alkanes but not their immobilizing actions. IMPLICATIONS: The
      results of this study suggest that the immobilizing actions of general
      anesthetics do not result from the inhibition of alpha(4beta2) neuronal nicotinic
      acetylcholine receptors. However, the inhibition of neuronal nicotinic
      acetylcholine receptors may account for the amnestic activities of general
      anesthetics and nonimmobilizers.

PMID- 12198041
TI  - Mice with glycine receptor subunit mutations are both sensitive and resistant to
      volatile anesthetics.
AB  - We used two mouse lines with glycine receptor mutations to determine whether
      glycine receptors might play an important role in anesthetic responses in vivo.
      Spastic (spA) mutants were slightly more sensitive (P = 0.02) to enflurane in the
      loss-of-righting reflex assay (50% effective concentration [EC(50)] = 1.17 +/-
      0.06 atm for controls versus 0.97 +/- 0.06 atm for spA) but were also
      substantially more resistant (P = 0.01) to enflurane in the tail clamp assay
      (EC(50) = 1.96 +/- 0.10 atm for controls versus 2.58 +/- 0.25 atm for spA). spA
      mice were also more sensitive to halothane (P < 0.001) in the loss-of-righting
      reflex assay (EC(50) = 0.81 +/- 0.03 atm for controls versus 0.57 +/- 0.04 atm
      for spA), but the responses of mutant and control mice to tail clamp in the
      presence of halothane were similar. Spasmodic control and mutant mice did not
      differ in their responses to the two drugs. Sleep time was substantially longer
      in both mutant mouse lines after injection of three hypnotics (midazolam,
      pentobarbital, and ethanol). Our results suggest a complex involvement of
      glycinergic pathways in mediating anesthetic responses. Greater sensitivity to
      the hypnotic effect of enflurane, halothane, midazolam, pentobarbital, and
      ethanol in mutant mice with diminished glycinergic capacity suggests that
      glycinergic activity is inversely related to hypnosis, whereas resistance to
      enflurane in the tail clamp assay suggests that glycinergic activity potentiates
      the minimum alveolar anesthetic concentration response. Halothane seems to share
      some, but not all, of enflurane's mechanisms, indicating that not all volatile
      anesthetics modulate glycinergic pathways equally. IMPLICATIONS: We tested two
      mouse lines with glycine receptor mutations to determine whether glycine
      receptors might play an important role in anesthetic responses in vivo. Both
      sensitivity and resistance to common anesthetics were observed in mutant mice,
      depending on the behavioral end-point evaluated.

PMID- 12198042
TI  - The effect of isoflurane on neutrophil selectin and beta(2)-integrin activation
      in vitro.
AB  - Isoflurane is reported to reduce ischemia-reperfusion injury. Lower expression of
      CD11b may be responsible for attenuated postischemic neutrophil adhesion to
      vascular endothelium. However, neutrophil adhesion to vascular endothelium is a
      multistep process involving several selectins and beta(2)-integrins. Therefore,
      we assessed whether isoflurane affects the activation of the selectins P-selectin
      glycoprotein ligand-1 (PSGL-1) and L-selectin and the beta(2)-integrins CD11a and
      CD11b. Whole blood was incubated for 60 min with 0.5 or 1 minimum alveolar
      anesthetic concentration (MAC) isoflurane. After incubation, neutrophils were
      activated with N-formyl-methionyl-leucyl-phenylalanine (FMLP) or phorbol-12
      myristate-13-acetate (PMA). Activation of adhesion molecules was evaluated via
      flow cytometry, and 1 MAC isoflurane reduced the expression of CD11a in the
      unstimulated samples. After stimulation with FMLP and PMA, shedding of L-selectin
      was lower in the presence of isoflurane. Furthermore, 1 MAC isoflurane reduced
      FMLP-induced activation of CD11a and CD11b compared with unexposed blood samples.
      These results demonstrate that isoflurane affects the activation of three
      adhesion molecules involved in the multistep process of neutrophil recruitment.
      First, isoflurane inhibits the activation of L-selectin, which mediates the
      neutrophil tethering and rolling on the vascular endothelium. Second, isoflurane
      attenuates the activation of both beta(2)-integrins-CD11a and CD11b-which mediate
      firm adhesion and transendothelial migration. IMPLICATIONS: Adhesion of
      neutrophils to endothelial cells in reperfusion injury is mediated by different
      adhesion molecules. This study indicates that the inhibiting effect of isoflurane
      on neutrophil recruitment may be mediated by a decreased activation of the L
      selectin and by attenuation of the activation of the beta(2)-integrins CD11a and
      CD11b.

PMID- 12198043
TI  - Pharmacokinetic/pharmacodynamic modeling of rocuronium in myasthenic patients is
      improved by taking into account the number of unbound acetylcholine receptors.
AB  - Patients with myasthenia gravis are more sensitive than healthy patients to
      nondepolarizing neuromuscular blocking drugs. We performed a
      pharmacokinetic/pharmacodynamic modeling study of rocuronium in eight myasthenic
      patients and eight matched control patients. Patients were anesthetized with
      propofol and sufentanil and a mixture of nitrous oxide/oxygen.
      Mechanomyographical monitoring of the adductor pollicis was applied. Rocuronium
      was infused at a rate of 25 micro g. kg(-1). min(-1) in myasthenic patients and
      116.7 micro g. kg(-1). min(-1) in control patients and was terminated at 70%
      neuromuscular block. Arterial blood samples were drawn during onset and offset of
      the block and for 4 h after the administration of rocuronium. Plasma
      concentrations were determined by high-performance liquid chromatography.
      Pharmacokinetic/pharmacodynamic modeling was performed by using the Sheiner model
      and the unbound receptor model (URM), which takes into account the number of
      unbound acetylcholine receptors. The effective concentration at 50% effect and
      the steepness of the concentration-effect relationship were significantly
      decreased in myasthenic patients. Both the URM and the Sheiner model provided an
      adequate fit in myasthenic patients. The acetylcholine receptor concentration was
      significantly decreased in myasthenic patients. The URM explains the observed
      differences in time course and potency, whereas the Sheiner model does not.
      IMPLICATIONS: We performed a pharmacokinetic/pharmacodynamic modeling study in
      myasthenic patients and control patients. The unbound receptor model, which takes
      into account the number of unbound acetylcholine receptors in the biophase, was
      introduced and compared with the model proposed by Sheiner.

PMID- 12198044
TI  - Propofol-sufentanil anesthesia for thyroid surgery: optimal concentrations for
      hemodynamic and electroencephalogram stability, and recovery features.
AB  - Hypnotics and opioids interact synergistically to block responses to surgery and
      different dose combinations may be used to provide adequate anesthesia. In this
      study, we sought to determine the optimal concentrations of propofol and
      sufentanil, given by target-controlled infusions, to ensure hemodynamic
      stability, adequate hypnosis (assessed by electroencephalogram bispectral index),
      and fast recovery for a moderately painful operation. Forty-five patients, ASA
      physical status I or II, undergoing thyroidectomy, were randomly assigned to a
      sufentanil target concentration (STC) that was maintained throughout surgery
      (0.1, 0.2, or 0.3 ng/mL). The propofol target concentration was adjusted to keep
      mean arterial blood pressure within 30% of a reference value, and bispectral
      index between 40 and 60. Adequate anesthesia was obtained in all groups.
      Hypertension and clinically dangerous movements were more frequent with the small
      STC, and hypotension requiring treatment was more frequent with the large STC.
      Propofol target concentration during surgery decreased significantly with
      increasing STC (median at thyroid removal 5.0, 4.0, and 2.5 microg/mL,
      respectively) as well as the propofol consumption (740, 668, 474 mg/h). The 0.3
      ng/mL STC significantly delayed the return of spontaneous breathing.
      IMPLICATIONS: Given as a target-controlled infusion for thyroid surgery,
      sufentanil 0.3 ng/mL for intubation and 0.2 ng/mL during surgery, combined with
      propofol 4 microg/mL (corresponding to a maintenance infusion rate of
      approximately 7-10 mg. kg(-1). h(-1)), is recommended to ensure both optimal
      intraoperative stability and fast recovery.

PMID- 12198045
TI  - The use of magnesium sulfate to prevent pain on injection of propofol.
AB  - IMPLICATIONS: Magnesium sulfate, 2.48 mmol, injected 20 s before the
      administration of propofol significantly reduced the incidence of pain caused by
      a propofol injection and may be useful in minimizing this common side effect.

PMID- 12198046
TI  - Issues in the design and interpretation of minimum alveolar anesthetic
      concentration (MAC) studies.
AB  - IMPLICATIONS: The two experimental designs (quantal and bracketing) used for
      population minimum alveolar anesthetic concentration studies give equivalent
      results. An expression relating variability in terms of Hill coefficients and SD
      is presented. Evolutionary implications of low population variability in
      anesthetic phenotypes is discussed.

PMID- 12198047
TI  - Factors associated with successful tracheal intubation of children with
      sevoflurane and no muscle relaxant.
AB  - Better definition of end points required to achieve successful tracheal
      intubation after induction with sevoflurane could improve patient care. The
      authors therefore designed a study that could determine, with meaningful
      confidence intervals, the time required to successfully intubate 80% of children
      by using 8% inspired sevoflurane and no muscle relaxant. We hypothesized that the
      time required could vary by age or body mass index. One-hundred fifty-three ASA
      physical status I or II patients received induction with 8% sevoflurane in 60%
      nitrous oxide with discontinuation of nitrous oxide 1 min after the start of the
      induction. The time until laryngoscopy remained close to the time required to
      achieve 80% successful intubation by varying induction time according to the
      success rate in each group of five patients. A probit model of induction time and
      age found that both were predictive of successful intubation (P values of 0.006
      and 0.02, respectively). The induction times needed to achieve 80% successful
      intubation were 137 s (95% confidence interval, 94.6-159 s) and 187 s (153-230 s)
      for ages 1-4 yr and 4-8 yr, respectively. The persistence of spontaneous
      ventilation at the time of laryngoscopy, despite attempts to control ventilation,
      was associated with poor intubation conditions (P < 0.001). IMPLICATIONS: To
      successfully intubate 80% of children by using sevoflurane and no muscle
      relaxant, induction times of 137 and 187 s were needed in children of 1-4 yr and
      4-8 yr, respectively.

PMID- 12198048
TI  - Colobronchial fistula in a pediatric patient: diagnostic value of isolated single
      lung ventilation and intraoperative use of high frequency oscillatory
      ventilation.
AB  - IMPLICATIONS: We describe the anesthetic management of a pediatric patient who
      underwent thoracotomy repair of a colobronchial fistula. Single-lung ventilation
      confirmed the diagnosis and the position of the fistula. In addition, the
      intraoperative use of high frequency oscillatory ventilation in combination with
      conventional ventilation of the nonoperative side is described.

PMID- 12198049
TI  - The use of transesophageal echocardiography to facilitate removal of a thoracic
      nail.
AB  - IMPLICATIONS: Transesophageal echocardiography may be useful in guiding detection
      and removal of thorax penetrating objects and for the monitoring of complications
      after removal of such objects.

PMID- 12198050
TI  - Pain as a factor complicating recovery and discharge after ambulatory surgery.
AB  - Pain complicates the recovery process after ambulatory surgery. We surveyed 175
      ambulatory surgery patients to determine pain severity, analgesic use,
      relationship of pain to duration of recovery, and the relative importance of
      various factors to predicting these outcomes. Multivariate regression analysis
      was used to determine unique contributions of predictor variables to outcome.
      Surgical procedures included knee arthroscopy (n = 50), hernia surgery (n = 25),
      pelvic laparoscopy (n = 25), transvaginal uterine surgery (n = 25), surgery for
      breast disease (n = 25), and plastic surgery (n = 25). Maximum pain (on a scale
      of 0-10) varied from 2.3 +/- 0.5 to 5.1 +/- 0.5 (mean +/- SE), depending on
      surgical procedure; 24% of patients had pain scores of > or =7, and 24% were
      delayed in Phase 1 recovery by pain. Pain scores were lower if local anesthetic
      or ketorolac was administered intraoperatively (22% and 26% respectively).
      Fentanyl dose during recovery correlated with maximum pain scores; fentanyl dose
      was 42% less if ketorolac was administered intraoperatively. In females, the
      recovery fentanyl dose increased in proportion to the intraoperative fentanyl
      dose. The maximum pain score was predictive of total recovery time (135, 172, and
      212 min of recovery for maximum pain scores of 0-3, 4-6, and 7-10, respectively;
      P < 0.001). We conclude that improvements in pain therapy are warranted to
      improve patient comfort and to expedite recovery. IMPLICATIONS: Moderate to
      severe pain is common after ambulatory surgery and is a frequent cause of delayed
      discharge. Postoperative pain, opioid-related side effects, and time to discharge
      were less when nonsteroidal antiinflammatory drugs or local anesthetics were used
      intraoperatively to prevent pain before patient awakening.

PMID- 12198051
TI  - A novel ambulatory intravenous holder: preliminary findings.
AB  - IMPLICATIONS: Many devices serve as portable systems for IV equipment but are
      expensive and use complex electronic controls. We present a novel device to
      facilitate safe ambulation of IV-dependent patients. This device was effective in
      delivering required therapeutic flow rates over time periods desired for
      unattended operation.

PMID- 12198052
TI  - Bispectral index in patients with target-controlled or manually-controlled
      infusion of propofol.
AB  - In this prospective, randomized study we compared bispectral index (BIS),
      hemodynamics, time to extubation, and the costs of target-controlled infusion
      (TCI) and manually-controlled infusion (MCI) of propofol. Forty patients
      undergoing first-time implantation of a cardioverter-defibrillator were included.
      Anesthesia was performed with remifentanil (0.2-0.3 micro g. kg(-1). min(-1)) and
      propofol. Propofol was used as TCI (plasma target concentration, 2.5-3.5 micro
      g/mL; n = 20) or MCI (3.0-4.0 mg. kg(-1). h(-1); n = 20). BIS, heart rate, and
      arterial blood pressure were measured at six data points: T1, before anesthesia;
      T2, after intubation; T3, after skin incision; T4, after first defibrillation;
      T5, after third defibrillation; and T6, after extubation. There were no
      significant hemodynamic differences between the two groups. BIS was significantly
      lower at T3 and T4 in the TCI group than in the MCI group. The mean dose of
      propofol was larger in TCI patients (5.8 +/- 1.4 mg. kg(-1). h(-1)) than in the
      MCI patients (3.7 +/- 0.6 mg. kg(-1). h(-1)) (P < 0.05), whereas doses of
      remifentanil did not differ. Time to extubation did not differ between the two
      groups (TCI, 13.7 +/- 5.3 min; MCI, 12.3 +/- 3.5 min). One patient in the MCI
      group had signs of intraoperative awareness without explicit memory after first
      defibrillation (BIS before shock, 49; after shock, 83). Costs were significantly
      less in the MCI group (34.83 US dollars) than in the TCI group (39.73 US
      dollars). BIS failed to predict the adequacy of anesthesia for the next painful
      stimulus. IMPLICATIONS: In this prospective, randomized study, bispectral index
      (BIS), hemodynamics, time to extubation, and costs of target-controlled infusion
      (TCI) and manually-controlled infusion of propofol were compared. TCI increased
      the amount of propofol used. BIS failed to predict the adequacy of anesthesia for
      the next painful stimulus.

PMID- 12198053
TI  - Clinical application of acoustic reflectometry in predicting the difficult
      airway.
AB  - Acoustic reflectometry, a noninvasive test that produces a length versus cross
      sectional area map of the airway, has been used to identify difficult-to
      tracheally intubate patients in a small retrospective case-control study. A
      critical airway volume of 40.2 mL separated those patients whose tracheas were
      impossible to intubate from those who were easily intubated. To determine if this
      technology was applicable for prospectively predicting difficult intubation and
      difficult ventilation in routine clinical practice, we performed a double
      blinded, prospective cohort study. Our a priori hypothesis was that small airway
      volumes in adults (<40.2 mL) would predict absolute inability to intubate. We
      conclude that by use of acoustic reflectometry, there was no relationship between
      inability to intubate, poor glottic visualization, and multiple laryngoscopies
      with airway volume. IMPLICATIONS: Acoustic reflectometry, a noninvasive test that
      uses sound to produce a length versus cross-sectional area map of the airway, was
      not able to predict inability to intubate, poor glottic visualization, and
      multiple laryngoscopies.

PMID- 12198054
TI  - Small carbon monoxide formation in absorbents does not correlate with small
      carbon dioxide absorption.
AB  - In this study we sought to determine whether an absorbent in which little carbon
      monoxide (CO) forms has a correspondingly small capacity to absorb carbon dioxide
      (CO(2)). Completely dried samples (600 g) of Baralyme (A), Dragersorb 800 (B),
      Dragersorb 800 Plus (C), Intersorb (D), Spherasorb (E), LoFloSorb (F), Superia
      (G), and Amsorb (H) were exposed to a flow of 0.5% (A-H; n = 4-5) and 4%
      isoflurane (F-H; n = 3) in pure oxygen at 5 L/min for 60 min. Downstream CO
      concentration, temperature, and isoflurane concentration were recorded every 60 s
      to calculate CO formation and isoflurane loss. The CO(2) absorption capacity of
      each brand was determined by passing 5.1% CO(2) in oxygen (flow, 250 mL/min)
      through untreated samples (30 g; n = 5) until the outlet CO(2) concentration
      reached 0.5%. CO formation was largest in absorbents containing potassium
      hydroxide (A and B) and negligible in absorbents not containing any alkali
      hydroxide (F-H). The outlet temperature correlated with CO formation, but the
      isoflurane loss did not. The duration of CO(2) absorption also did not correlate
      with CO formation. We conclude that absorbents that allow only very little CO
      formation are not necessarily poor CO(2) absorbents. IMPLICATIONS: In an in vitro
      study, carbon dioxide (CO(2)) absorption capacity and possible carbon monoxide
      (CO) formation were tested in different absorbent brands. Absorbents with very
      small CO formation are not necessarily poor CO(2) absorbents.

PMID- 12198055
TI  - The use of a uniquely designed anesthetic scavenging hood to reduce operating
      room anesthetic gas contamination during general anesthesia.
AB  - Numerous studies have suggested that chronic exposure to trace levels of
      anesthetic gas is harmful to operating room (OR) personnel. In the delivery of
      pediatric general anesthesia, an uncuffed endotracheal tube (ETT) is normally
      used which can result in considerable volatile anesthetic and nitrous oxide
      contamination of the OR. In this report, we present a method to reduce exposure
      to these anesthetic gases by means of an anesthetic scavenging hood (ASH). The
      ASH was used on six pediatric patients undergoing general endotracheal anesthesia
      via an uncuffed ETT. Measurements of all ambient gas levels were made 6 in.
      horizontally from the patient's ear and 6 in. from the table surface. The
      application of the vacuum source to the ASH resulted in a very significant (P <
      0.01, paired t-test) decrease in levels of ambient anesthetic gas, with no
      measurable change in ventilatory variables or changes in body temperature (P >
      0.05, paired t-test). Discontinuation of the vacuum force to the ASH resulted in
      a marked increase in ambient levels of anesthetic gas. We conclude that the ASH
      is extremely effective in reducing waste anesthetic gas associated with
      anesthesia administered via an uncuffed ETT. The ASH may be a valuable and cost
      effective addition in the OR for both reducing ambient anesthetic waste gas
      levels and conserving patient heat. IMPLICATIONS: Chronic exposure to trace
      levels of anesthetic gas is harmful to operating room personnel, especially in
      the delivery of pediatric general anesthesia via an uncuffed endotracheal tube.
      The anesthetic scavenging hood is a cost-effective and efficient method to reduce
      these waste anesthetic gases, and it offers patient heat conservation.

PMID- 12198056
TI  - Intrathecal magnesium prolongs fentanyl analgesia: a prospective, randomized,
      controlled trial.
AB  - Magnesium is a noncompetitive, N-methyl-D-aspartate receptor antagonist that does
      not effectively cross the blood-brain barrier when given IV. Intrathecal
      magnesium potentiates opioid antinociception in rats, and the safety of
      intrathecal magnesium has been demonstrated in animals. This is the first
      prospective human study evaluating whether intrathecal magnesium could prolong
      spinal opioid analgesia. Fifty-two patients requesting analgesia for labor were
      randomized to receive either intrathecal fentanyl 25 micro g plus saline or
      fentanyl 25 micro g plus magnesium sulfate 50 mg as part of a combined spinal
      epidural technique. The duration of analgesia of the intrathecal drug combination
      was defined by the time of patient request for additional analgesia. There was
      significant prolongation in the median duration of analgesia (75 min) in the
      magnesium plus fentanyl group compared with the fentanyl alone group (60 min).
      There was no associated increase in adverse events in the group that received
      intrathecal magnesium. Larger doses of intrathecal magnesium were not studied in
      this group of patients because of the limitations on cephalad spread when
      hyperbaric solutions are injected in the sitting position. Our data indicate that
      intrathecal magnesium prolongs spinal opioid analgesia in humans and suggest that
      the availability of an intrathecal N-methyl-D-aspartate antagonist could be of
      clinical importance for pain management. IMPLICATIONS: Magnesium occurs naturally
      in the spinal cord and blocks the NMDA glutamate channel. In animal studies,
      intrathecal magnesium sulfate improves spinal morphine analgesia. For patients
      receiving spinal analgesia for labor, the addition of magnesium sulfate to the
      opioid fentanyl prolonged analgesia with no increase of side effects.

PMID- 12198057
TI  - The influence of parecoxib, a parenteral cyclooxygenase-2 specific inhibitor, on
      the pharmacokinetics and clinical effects of midazolam.
AB  - Parecoxib, a parenteral cyclooxygenase-2 inhibitor, is undergoing clinical
      development as an analgesic/antiinflammatory drug for perioperative use.
      Parecoxib, an inactive prodrug, is hydrolyzed in vivo to valdecoxib, a substrate
      for hepatic cytochrome P450 (CYP) 3A4. Thus, potential exists for interactions
      with other CYP3A4 substrates. In this investigation, we determined the influence
      of parecoxib on the pharmacokinetics and clinical effects of midazolam, a CYP3A4
      substrate, in volunteers. This was a randomized, balanced crossover, placebo
      controlled, double-blinded clinical investigation. Twelve healthy subjects aged
      23-41 yr were studied after providing IRB-approved informed consent. Midazolam
      0.07 mg/kg IV infusion was administered 1 h after placebo (control) or parecoxib
      40 mg IV. Venous midazolam concentrations were determined by using liquid
      chromatography-mass spectrometry/mass spectrometry assay. Pharmacokinetic
      variables were determined by noncompartmental analysis. Pharmacodynamic
      measurements included clinical end-points, cognitive function (memory; digit
      symbol substitution tests), subjective self-assessment of recovery (visual analog
      scales), and bispectral index. Midazolam plasma concentrations were similar
      between placebo and parecoxib-treated subjects. No differences were found in
      midazolam pharmacokinetics (maximal observed plasma concentration, clearance,
      elimination half-life, volume of distribution) or pharmacodynamics (clinical end
      points, digit symbol substitution tests, memory, visual analog scales, bispectral
      index). Single-bolus parecoxib does not alter the pharmacokinetics or
      pharmacodynamics of midazolam infusion. Parecoxib did not affect CYP3A4 activity
      as assessed using midazolam clearance as the in vivo probe. IMPLICATIONS:
      Parecoxib, a parenteral cyclooxygenase-2 inhibitor intended for perioperative use
      as an analgesic/antiinflammatory drug, is a substrate for hepatic cytochrome P450
      3A4. The potential for a drug interaction with midazolam, an in vivo CYP3A4
      probe, was tested in healthy volunteers. Single-bolus parecoxib does not alter
      the pharmacokinetics or pharmacodynamics of midazolam.

PMID- 12198059
TI  - The prediction of defibrillation outcome using a new combination of mean
      frequency and amplitude in porcine models of cardiac arrest.
AB  - We estimated the predictive power with respect to defibrillation outcome of
      ventricular fibrillation (VF) mean frequency (FREQ), mean peak-to-trough
      amplitude (AMPL), and their combination. We examined VF electrocardiogram signals
      of 64 pigs from 4 different cardiac arrest models with different durations of
      untreated VF, different durations of cardiopulmonary resuscitation, and use of
      different drugs (epinephrine, vasopressin, N-nitro-L-arginine methyl ester, or
      saline placebo). The frequency domain was restricted to the range from 4.33 to 30
      Hz. In the 10-s epoch between 20 and 10 s before the first defibrillation shock,
      FREQ and AMPL were estimated. We introduced the survival index (SI; 0.68 Hz(-1).
      FREQ + 12.69 mV(-1). AMPL) by use of multiple logistic regression. Kruskal-Wallis
      nonparametric one-way analysis was used to analyze the different porcine models
      for significant difference. The variables FREQ, AMPL, and SI were compared with
      defibrillation outcome by means of univariate logistic regression and receiver
      operating characteristic curves. SI increased predictive power compared with AMPL
      or FREQ alone, resulting in 89% sensitivity and 86% specificity. The
      probabilities of predicting defibrillation outcome for FREQ, AMPL, and SI were
      0.85, 0.89 and 0.90, respectively. FREQ, AMPL, and SI values were not sensitive
      in regard to the four different cardiac arrest models but were significantly
      different for vasopressin and epinephrine animals. IMPLICATIONS: We present a
      retrospective data analysis to evaluate the predictive power of different
      ventricular fibrillation electrocardiogram variables in pigs with respect to
      defibrillation outcome. We showed that our combination of variables leads to an
      improved forecast, which may help to reduce harmful unsuccessful defibrillation
      attempts.

PMID- 12198058
TI  - Combination spinal analgesic chemotherapy: a systematic review.

PMID- 12198060
TI  - Prehospital analgesia with acupressure in victims of minor trauma: a prospective,
      randomized, double-blinded trial.
AB  - Untreated pain during the transportation of patients after minor trauma is a
      common problem in emergency medicine. Because paramedics usually are not allowed
      to perform invasive procedures or to give drugs for pain treatment, a
      noninvasive, nondrug-based method would be helpful. Acupressure is a traditional
      Chinese treatment for pain that is based on pain relief followed by a short
      mechanical stimulation of specific points. Consequently, we tested the hypothesis
      that effective pain therapy is possible by paramedics who are trained in
      acupressure. In a double-blinded trial we included 60 trauma patients. We
      randomly assigned them into three groups ("true points," "sham-points," and "no
      acupressure"). An independent observer, blinded to the treatment assignment,
      recorded vital variables and visual analog scales for pain and anxiety before and
      after treatment. At the end of transport, we asked for ratings of overall
      satisfaction. For statistical evaluation, one-way analysis of variance and the
      Scheffe F test were used. P < 0.05 was considered statistically significant.
      Morphometric and demographic data and potential confounding factors such as age,
      sex, pain, anxiety, blood pressure, and heart rate before treatment did not
      differ among the groups. At the end of transport we found significantly less
      pain, anxiety, and heart rate and a greater satisfaction in the "true points"
      groups (P < 0.01). Our results show that acupressure is an effective and simple
      to-learn treatment of pain in emergency trauma care and leads to an improvement
      of the quality of care in emergency transport. We suggest that this technique is
      easy to learn and risk free and may improve paramedic-based rescue systems.
      IMPLICATIONS: We tested, in a double-blinded manner, the hypothesis that
      acupressure could be an effective pain therapy in minor-trauma patients. Our
      results show that acupressure is an effective and simple-to-learn treatment of
      pain in emergency medical care and can improve the quality of care.

PMID- 12198061
TI  - The dose-sparing effect of clonidine added to ropivacaine for labor epidural
      analgesia.
AB  - To determine the effects of clonidine with ropivacaine during epidural labor
      analgesia, we studied 66 nulliparous women in early active labor. Women were
      randomized to receive ropivacaine 0.1% 8 mL plus 75 microg of clonidine (Group
      1), ropivacaine 0.2% 8 mL plus 0.5 mL of NaCl 0.9% (Group 2), or ropivacaine 0.2%
      8 mL plus 75 microg of clonidine (Group 3) 5 min after a bupivacaine 7.5 mg with
      epinephrine 15 microg test dose. Upon request, additional analgesia with
      ropivacaine 0.1% 8 mL followed by ropivacaine 0.2% 8 mL/h was administered. With
      clonidine, duration of analgesia was increased (132 +/- 48 min [Group 1] and 154
      +/- 42 min [Group 3] versus 91 +/- 44 min [Group 2]; P < 0.05), and total
      ropivacaine dose over the first 4 h was significantly reduced (40.5 +/- 15 mg
      [Group 1] and 47.0 +/- 16 mg [Group 3] versus 72.5 +/- 18 mg [Group 2]; P <
      0.01). The incidence of more profound motor block was more frequent in Group 2 (P
      < 0.05). Although there was a trend for more women receiving clonidine to require
      ephedrine for treatment of hypotension, this did not seem to have an impact on
      fetal outcome or incidence of cesarean deliveries for nonreassuring fetal heart
      rate tracings. This study demonstrates the dose-sparing effect of clonidine when
      added to ropivacaine. IMPLICATIONS: The effect of adding 75 microg of clonidine
      to ropivacaine for epidural labor analgesia was studied. Clonidine increased
      analgesia duration and produced dose sparing compared with ropivacaine alone.
      Despite a tendency for hypotension in women receiving clonidine, there was no
      apparent effect on delivery mode or neonatal outcome.

PMID- 12198062
TI  - The effect of clonidine on the minimum local analgesic concentration of epidural
      ropivacaine during labor.
AB  - On the basis of the determination of minimum local analgesic concentration
      (MLAC), ropivacaine has been demonstrated to be less potent than bupivacaine
      during the first stage of labor. In this study we assessed the effect of
      clonidine on the MLAC of ropivacaine. Seventy-seven parturients of mixed parity
      requesting epidural analgesia for labor (cervical dilation, 3-7 cm) were included
      in the study. They received an epidural bolus of either ropivacaine (n = 30),
      ropivacaine plus clonidine 30 microg (n = 28), or ropivacaine plus clonidine 60
      microg (n = 19) in the second part of the study. The concentration of the
      ropivacaine solution was determined by the response of the previous parturient in
      that group by using an up-down sequential allocation. A visual analog pain score
      of < or =10 mm within 30 min after the epidural bolus (20 mL) was considered an
      effective response. An effective result directed a 0.01% wt/vol decrement for the
      next patient. An ineffective result directed a 0.01% wt/vol increment. The MLAC
      of ropivacaine was 0.097% wt/vol (95% confidence interval, 0.085%-0.108%). It was
      unaffected by a 30-microg dose of epidural clonidine (0.081% [0.045%-0.117%]) but
      was significantly decreased by a 60-microg clonidine dose (0.035% [0.024%
      0.046%]) (P < 0.001). This study documents a decrease in the MLAC of ropivacaine
      by clonidine, significant for a 60- microg dose. IMPLICATIONS: Epidural
      ropivacaine potency in labor can be increased by the addition of epidural
      clonidine. This study demonstrates that 60 microg of epidural clonidine
      significantly decreases the minimum local analgesic concentration of ropivacaine
      during the first stage of labor but is associated with sedation.

PMID- 12198063
TI  - A randomized controlled trial examining the effect of naproxen on analgesia
      during the second day after cesarean delivery.
AB  - Whereas nonsteroidal antiinflammatory drugs augment spinal morphine on Day l, the
      analgesia gained by simply combining these drugs with conventional "on request"
      oral regimens on Day 2 is less clear. In this trial, we randomized 80 women
      undergoing elective cesarean delivery with spinal morphine (0.2 mg) to receive
      naproxen (500 mg) or placebo every 12 h after surgery. Both groups received
      conventional therapy with acetaminophen with codeine (on request) and rescue IM
      opioids. Incision pain on sitting (IPS), incision pain at rest, uterine cramping,
      and gas pain were evaluated with visual analog scales (0-100). Worst interval
      pain (0-10), analgesic use, and side effects were measured over 72 h. At 36 h
      (primary outcome), naproxen use was associated with reductions in IPS (38.2 +/-
      26.0 versus 51.4 +/- 25.7; P = 0.05), incision pain at rest, uterine cramping,
      and worst interval pain scores. Clinically modest, statistically significant
      reductions in IPS (P = 0.0001) and opioid use were found over time (P < 0.0l).
      Reductions in the incidence of inadequate analgesia and improvements in overall
      pain relief (P = 0.0006) on Day l did not persist on Day 2 (overall pain relief,
      P = 0.057; inadequate analgesia, 24% naproxen versus 27% controls; P = 1.00). The
      addition of regular doses of naproxen to conventional oral pain therapy after
      cesarean delivery leads to reductions in IPS at 36 h and pain over Day 2 but does
      not reduce the incidence of inadequate analgesia. IMPLICATIONS: This randomized
      trial suggests that adding regular doses of naproxen to conventional "on request"
      acetaminophen and codeine therapy provides small reductions in pain on the second
      day after cesarean delivery. The greatest effects occur at 36 h, when pain peaks.

PMID- 12198064
TI  - The analgesic efficacy of bilateral combined superficial and deep cervical plexus
      block administered before thyroid surgery under general anesthesia.
AB  - In this study we evaluated the analgesic efficacy of combined deep and
      superficial cervical plexus block in patients undergoing thyroidectomy under
      general anesthesia. For this purpose, 39 patients undergoing elective thyroid
      surgery were randomized to receive a bilateral combined deep and superficial
      cervical block (14 mL per side) with saline (Group 1; n = 13), ropivacaine 0.5%
      (Group 2; n = 13), or ropivacaine 0.5% plus clonidine 7.5 microg/mL (Group 3; n =
      13). Deep cervical plexus block was performed with a single injection (8 mL) at
      the C3 level. Superficial cervical plexus block consisted of a subcutaneous
      injection (6 mL) behind the lateral border of the sternocleidomastoid muscle.
      During surgery, the number of additional alfentanil boluses was significantly
      reduced in Groups 2 and 3 compared with Group 1 (1.3 +/- 1.0 and 1.1 +/- 1.0 vs
      2.6 +/- 1.0; P < 0.05). After surgery, the opioid and non-opioid analgesic
      requirements were also significantly reduced in Groups 2 and 3 (P < 0.05) during
      the first 24 h. Except for one patient in Group 3, who experienced transient
      anesthesia of the brachial plexus, no side effect was noted in any group. We
      conclude that combined deep and superficial cervical plexus block is an effective
      technique to alleviate pain during and immediately after thyroidectomy.
      IMPLICATIONS: Combined deep and superficial cervical plexus block is an effective
      technique to reduce opioid requirements during and after thyroid surgery.

PMID- 12198065
TI  - Prophylactic IM small-dose phenylephrine blunts spinal anesthesia-induced
      hypotensive response during surgical repair of hip fracture in the elderly.
AB  - In a double-blinded, placebo-controlled, randomized study, we evaluated the
      effect of prophylactic IM phenylephrine at doses of 1.5 and 3 mg on hyperbaric
      tetracaine spinal anesthesia-induced hypotension in 90 normotensive and
      hypertensive patients aged >65 yr undergoing surgery for hip fracture. Thirty
      normotensive patients received 1.5 or 3 mg of phenylephrine IM (N/P-1.5 and N/P
      3.0 groups; n = 15 in each), whereas controls received saline (N/C group; n =
      15), and 45 hypertensive patients were treated in a similar manner (H/P-1.5, H/P
      3.0, and H/C groups; n = 15 in each). All groups had a peak sensory block height
      of T9, with a range of T8 to T10. The incidence of hypotension (>25% decrease in
      mean arterial blood pressure [MAP] from baseline) was significantly lower in the
      patients who received phenylephrine 1.5 or 3 mg than in the controls, both in the
      normotensive and hypertensive groups (P < 0.01). The N/P-3.0 and N/P-1.5 groups
      and the H/P-3.0 group had significantly lower percentage reductions in MAP (P <
      0.05) and required significantly smaller doses of rescue IV ephedrine (P < 0.05)
      than did the N/C group or the H/C group. The H/P-1.5 group also required
      significantly less rescue IV ephedrine (P < 0.05), although it was not sufficient
      to significantly attenuate the percentage decrease in MAP compared with that in
      the H/C group. Bradycardia (heart rate <50 bpm) as an adverse effect after IM
      administration of phenylephrine was not observed in any of the groups.
      Hypertension (MAP >20% increase from baseline) after medication occurred in the
      N/P-3.0 and H/P-3.0 groups, but not in the N/P-1.5 and H/P-1.5 groups. We
      conclude that prophylactic IM injection of 1.5 mg of phenylephrine is a safe
      (defined as the inhibition of bradycardia and hypertension) and effective means
      of reducing the incidence of hypotension associated with spinal anesthesia in
      normotensive and hypertensive elderly patients. IMPLICATIONS: We evaluated the
      efficacy and safety of small-dose IM phenylephrine for prophylaxis against spinal
      anesthesia-induced hypotension in normotensive and hypertensive elderly patients.
      Phenylephrine 1.5 mg IM was effective for reducing the incidence of hypotension
      and avoided adverse effects.

PMID- 12198066
TI  - Transient neurologic syndrome in a patient receiving hypobaric lidocaine in the
      prone jack-knife position.
AB  - IMPLICATIONS: The occurrence of transient neurologic symptoms after hypobaric
      lidocaine spinal anesthesia has not been reported, and may suggest sciatic
      stretch with neural ischemia rather than maldistribution as the cause of this
      syndrome.

PMID- 12198067
TI  - Shearing of a peripheral nerve catheter.
AB  - IMPLICATIONS: We report a previously undescribed complication of peripheral nerve
      catheter placement. The catheter was sheared when its stylet was removed with the
      placement needle still in the tissues. The lost distal fragment was identified
      with computed tomography scanning.

PMID- 12198068
TI  - Unsolicited paresthesias with nerve stimulator: case reports of four patients.
AB  - IMPLICATIONS: Unsolicited paresthesias may occur when a nerve stimulator is used
      and may indicate valid proximity to the nerve. This phenomenon suggests that
      nerve stimulator use does not protect against unplanned direct contact with
      peripheral nerves during performance of a nerve block on an obtunded patient.

PMID- 12198069
TI  - Comparing methods of administering high-frequency jet ventilation in a model of
      laryngotracheal stenosis.
AB  - We administered high-frequency jet ventilation (HFJV) to a tracheal-lung model
      with connectors of internal diameter 2.5-8.5 mm to simulate ventilation through
      varying degrees of laryngotracheal stenosis. With reductions in diameter, end
      expiratory pressure (EEP) and peak inspiratory pressure (PIP) increased. During
      supraglottic, translaryngeal, and transtracheal HFJV, respectively, EEP was > or
      =10 mm Hg at diameters narrower than 5.5, 4.0, and 3.5 cm, and PIP was >20 mm Hg
      at diameters narrower than 5.5, 3.5, and 3.0 cm. EEP and PIP were greater during
      supraglottic HFJV than during translaryngeal and transtracheal HFJV (P < 0.01).
      At diameters of <3.5 and 4.0 cm, respectively, PIP and EEP increased and were
      significantly greater (P < 0.01) during translaryngeal HFJV than during
      transtracheal HFJV. In a second experiment, the degree of ventilation and air
      entrainment was assessed by administering nitrous oxide 4 L/min to the model.
      Nitrous oxide concentrations were significantly (P < 0.01) smaller and nitrogen
      concentrations were significantly (P < 0.01) larger during supraglottic HFJV than
      either translaryngeal or transtracheal HFJV. The larger EEP and PIP associated
      with supraglottic HFJV may be attributable to increased ventilation and air
      entrainment compared with translaryngeal and transtracheal HFJV. IMPLICATIONS:
      Ventilatory driving pressure during supraglottic high-frequency jet ventilation
      may be reduced to minimize high airway pressures and hence the potential for
      pulmonary barotrauma in patients with laryngotracheal stenosis.

PMID- 12198070
TI  - A comparison of the laryngeal mask airway ProSeal and the laryngeal tube airway
      in paralyzed anesthetized adult patients undergoing pressure-controlled
      ventilation.
AB  - We compared the laryngeal mask airway ProSeal (PLMA) and the laryngeal tube
      airway (LTA), two new extraglottic airway devices, with respect to: 1) insertion
      success rates and times, 2) efficacy of seal, 3) ventilatory variables during
      pressure-controlled ventilation, 4) tidal volume in different head/neck
      positions, and 5) airway interventional requirements. One-hundred-twenty
      paralyzed anesthetized ASA physical status I and II adult patients were randomly
      allocated to the PLMA or LTA for airway management. A standardized anesthesia
      protocol was followed by two anesthesiologists experienced with both devices. The
      criteria for an effective airway included a minimal expired tidal volume of 6
      mL/kg during pressure-controlled ventilation at 17 cm H(2)O with no oropharyngeal
      leak or gastric insufflation. First attempt success rates at achieving an
      effective airway were similar (PLMA: 85%; LTA: 87%), but after 3 attempts,
      success was more frequent for the PLMA (100% versus 92%, P = 0.02). Effective
      airway time was similar. Oropharyngeal leak pressure was larger for PLMA at 50%
      maximal recommended cuff volume (29 +/- 7 versus 21 +/- 6 cm H(2)O, P < 0.0001),
      but was similar at the maximal recommended cuff volume (33 +/- 7 versus 31 +/- 8
      cm H(2)O). Tidal volumes (614 +/- 173 versus 456 +/- 207 mL, P < 0.0001) were
      larger and ETCO(2) (33 +/- 9 versus 40 +/- 11 mm Hg, P = 0.0001) lower for the
      PLMA. The number of airway interventions was significantly less frequent for the
      PLMA. Airway obstruction was more common with the LTA. When comparing mean tidal
      volumes in different head/neck positions, the quality of airway was unchanged in
      56 of 60 patients (93%) with the PLMA and 42 of 55 (76%) with the LTA (P = 0.01).
      The PLMA offers advantages over the LTA in most technical aspects of airway
      management in paralyzed patients undergoing pressure-controlled ventilation.
      IMPLICATIONS: The laryngeal mask airway ProSeal offers advantages over the
      laryngeal tube airway in most technical aspects of airway management in paralyzed
      patients undergoing pressure-controlled ventilation.

PMID- 12198071
TI  - Myoclonic seizure in the postanesthesia care unit after thoracic laminectomy.
AB  - IMPLICATIONS: We report a patient who developed myoclonic seizure in the
      postanesthesia care unit after thoracic laminectomy. Expeditious diagnostic
      evaluation of unrecognized dura tear during surgery must be instituted
      immediately to avoid untoward sequelae. Specific treatment in addition to
      supportive care is required if the diagnosis is to be clearly identified.

PMID- 12198072
TI  - Evaluation of a new posterior subgluteus approach to sciatic nerve.

PMID- 12198073
TI  - Is beta-blockade a confounding variable?

PMID- 12198074
TI  - Successful use of laryngeal mask airway for a patient with tracheal stenosis with
      tracheobronchopathia osteochondroplastica.

PMID- 12198075
TI  - Pharmacokinetics of transdermal fentanyl.

PMID- 12198076
TI  - Infection after radial artery catheterization.

PMID- 12198077
TI  - Central venous access in morbidly obese patients.

PMID- 12198078
TI  - Intra-aircraft patient transport.

PMID- 12198079
TI  - A further consideration on Mallampati class and laryngoscopy grade.

PMID- 12198080
TI  - Brachial plexus infraclavicular block success rate and appropriate endpoints.

PMID- 12198081
TI  - A high-risk endotracheal tube exchanger.

PMID- 12198082
TI  - Placing central venous catheters: gold standard for adult and silver standard for
      pediatric patients?

PMID- 12198083
TI  - Precipitation of protamine by cefazolin.

PMID- 12198084
TI  - Addition of anesthesia patient simulator is an improvement to evaluation process.

PMID- 12198085
TI  - B vitamins and nitrous oxide.

PMID- 12198086
TI  - Setting the stage for molecular dissection of the regulatory components of BK
      channels.

PMID- 12198087
TI  - Coupling between voltage sensor activation, Ca2+ binding and channel opening in
      large conductance (BK) potassium channels.
AB  - To determine how intracellular Ca(2+) and membrane voltage regulate the gating of
      large conductance Ca(2+)-activated K(+) (BK) channels, we examined the steady
      state and kinetic properties of mSlo1 ionic and gating currents in the presence
      and absence of Ca(2+) over a wide range of voltage. The activation of unliganded
      mSlo1 channels can be accounted for by allosteric coupling between voltage sensor
      activation and the closed (C) to open (O) conformational change (Horrigan, F.T.,
      and R.W. Aldrich. 1999. J. Gen. Physiol. 114:305-336; Horrigan, F.T., J. Cui, and
      R.W. Aldrich. 1999. J. Gen. Physiol. 114:277-304). In 0 Ca(2+), the steady-state
      gating charge-voltage (Q(SS)-V) relationship is shallower and shifted to more
      negative voltages than the conductance-voltage (G(K)-V) relationship. Calcium
      alters the relationship between Q-V and G-V, shifting both to more negative
      voltages such that they almost superimpose in 70 microM Ca(2+). This change
      reflects a differential effect of Ca(2+) on voltage sensor activation and channel
      opening. Ca(2+) has only a small effect on the fast component of ON gating
      current, indicating that Ca(2+) binding has little effect on voltage sensor
      activation when channels are closed. In contrast, open probability measured at
      very negative voltages (less than -80 mV) increases more than 1,000-fold in 70
      microM Ca(2+), demonstrating that Ca(2+) increases the C-O equilibrium constant
      under conditions where voltage sensors are not activated. Thus, Ca(2+) binding
      and voltage sensor activation act almost independently, to enhance channel
      opening. This dual-allosteric mechanism can reproduce the steady-state behavior
      of mSlo1 over a wide range of conditions, with the assumption that activation of
      individual Ca(2+) sensors or voltage sensors additively affect the energy of the
      C-O transition and that a weak interaction between Ca(2+) sensors and voltage
      sensors occurs independent of channel opening. By contrast, macroscopic I(K)
      kinetics indicate that Ca(2+) and voltage dependencies of C-O transition rates
      are complex, leading us to propose that the C-O conformational change may be
      described by a complex energy landscape.

PMID- 12198089
TI  - Na+ block and permeation in a K+ channel of known structure.
AB  - The effects of intracellular Na(+) were studied on K(+) and Rb(+) currents
      through single KcsA channels. At low voltage, Na(+) produces voltage-dependent
      block, which becomes relieved at high voltage by a "punchthrough" mechanism
      representing Na(+) escaping from its blocking site through the selectivity
      filter. The Na(+) blocking site is located in the wide, hydrated vestibule, and
      it displays unexpected selectivity for K(+) and Rb(+) against Na(+). The voltage
      dependence of Na(+) block reflects coordinated movements of the blocker with
      permeant ions in the selectivity filter.

PMID- 12198088
TI  - Calcium-activated K+ channels of mouse beta-cells are controlled by both store
      and cytoplasmic Ca2+: experimental and theoretical studies.
AB  - A novel calcium-dependent potassium current (K(slow)) that slowly activates in
      response to a simulated islet burst was identified recently in mouse pancreatic
      beta-cells (Gopel, S.O., T. Kanno, S. Barg, L. Eliasson, J. Galvanovskis, E.
      Renstrom, and P. Rorsman. 1999. J. Gen. Physiol. 114:759-769). K(slow) activation
      may help terminate the cyclic bursts of Ca(2+)-dependent action potentials that
      drive Ca(2+) influx and insulin secretion in beta-cells. Here, we report that
      when [Ca(2+)](i) handling was disrupted by blocking Ca(2+) uptake into the ER
      with two separate agents reported to block the sarco/endoplasmic calcium ATPase
      (SERCA), thapsigargin (1-5 microM) or insulin (200 nM), K(slow) was transiently
      potentiated and then inhibited. K(slow) amplitude could also be inhibited by
      increasing extracellular glucose concentration from 5 to 10 mM. The biphasic
      modulation of K(slow) by SERCA blockers could not be explained by a minimal
      mathematical model in which [Ca(2+)](i) is divided between two compartments, the
      cytosol and the ER, and K(slow) activation mirrors changes in cytosolic calcium
      induced by the burst protocol. However, the experimental findings were reproduced
      by a model in which K(slow) activation is mediated by a localized pool of
      [Ca(2+)] in a subspace located between the ER and the plasma membrane. In this
      model, the subspace [Ca(2+)] follows changes in cytosolic [Ca(2+)] but with a
      gradient that reflects Ca(2+) efflux from the ER. Slow modulation of this
      gradient as the ER empties and fills may enhance the role of K(slow) and [Ca(2+)]
      handling in influencing beta-cell electrical activity and insulin secretion.

PMID- 12198090
TI  - Calmodulin binding to the 3614-3643 region of RyR1 is not essential for
      excitation-contraction coupling in skeletal myotubes.
AB  - Calmodulin is a ubiquitous Ca(2+) binding protein that modulates the in vitro
      activity of the skeletal muscle ryanodine receptor (RyR1). Residues 3614-3643 of
      RyR1 comprise the CaM binding domain and mutations within this region result in a
      loss of both high-affinity Ca(2+)-bound calmodulin (CaCaM) and Ca(2+)-free CaM
      (apoCaM) binding (L3624D) or only CaCaM binding (W3620A). To investigate the
      functional role of CaM binding to this region of RyR1 in intact skeletal muscle,
      we compared the ability of RyR1, L3624D, and W3620A to restore excitation
      contraction (EC) coupling after expression in RyR1-deficient (dyspedic) myotubes.
      W3620A-expressing cells responded normally to 10 mM caffeine and 500 microM 4
      chloro-m-cresol (4-cmc). Interestingly, L3624D-expressing cells displayed a
      bimodal response to caffeine, with a large proportion of cells ( approximately
      44%) showing a greatly attenuated response to caffeine. However, high and low
      caffeine-responsive L3624D-expressing myotubes exhibited Ca(2+) transients of
      similar magnitude after activation by 4-cmc (500 microM) and electrical
      stimulation. Expression of either L3624D or W3620A in dyspedic myotubes restored
      both L-type Ca(2+) currents (retrograde coupling) and voltage-gated SR Ca(2+)
      release (orthograde coupling) to a similar degree as that observed for wild-type
      RyR1, although L-current density was somewhat larger and activated at more
      hyperpolarized potentials in W3620A-expressing myotubes. The results indicate
      that CaM binding to the 3614-3643 region of RyR1 is not essential for voltage
      sensor activation of RyR1.

PMID- 12198091
TI  - Comparison of simulated and measured calcium sparks in intact skeletal muscle
      fibers of the frog.
AB  - Calcium sparks in frog intact skeletal muscle fibers were modeled as
      stereotypical events that arise from a constant efflux of Ca(2+) from a point
      source for a fixed period of time (e.g., 2.5 pA of Ca(2+) current for 4.6 ms; 18
      degrees C). The model calculates the local changes in the concentrations of free
      Ca(2+) and of Ca(2+) bound to the major intrinsic myoplasmic Ca(2+) buffers
      (troponin, ATP, parvalbumin, and the SR Ca(2+) pump) and to the Ca(2+) indicator
      (fluo-3). A distinctive feature of the model is the inclusion of a binding
      reaction between fluo-3 and myoplasmic proteins, a process that strongly affects
      fluo-3's Ca(2+)-reaction kinetics, its apparent diffusion constant, and hence the
      morphology of sparks. DeltaF/F (the change in fluo-3's fluorescence divided by
      its resting fluorescence) was estimated from the calculated changes in fluo-3
      convolved with the microscope point-spread function. To facilitate comparisons
      with measured sparks, noise and other sources of variability were included in a
      random repetitive fashion to generate a large number of simulated sparks that
      could be analyzed in the same way as the measured sparks. In the initial
      simulations, the binding of Ca(2+) to the two regulatory sites on troponin was
      assumed to follow identical and independent binding reactions. These simulations
      failed to accurately predict the falling phase of the measured sparks. A second
      set of simulations, which incorporated the idea of positive cooperativity in the
      binding of Ca(2+) to troponin, produced reasonable agreement with the
      measurements. Under the assumption that the single channel Ca(2+) current of a
      ryanodine receptor (RYR) is 0.5-2 pA, the results suggest that 1-5 active RYRs
      generate an average Ca(2+) spark in a frog intact muscle fiber.

PMID- 12198092
TI  - Mechanism of tacrine block at adult human muscle nicotinic acetylcholine
      receptors.
AB  - We used single-channel kinetic analysis to study the inhibitory effects of
      tacrine on human adult nicotinic receptors (nAChRs) transiently expressed in HEK
      293 cells. Single channel recording from cell-attached patches revealed
      concentration- and voltage-dependent decreases in mean channel open probability
      produced by tacrine (IC(50) 4.6 microM at -70 mV, 1.6 microM at -150 mV). Two
      main effects of tacrine were apparent in the open- and closed-time distributions.
      First, the mean channel open time decreased with increasing tacrine concentration
      in a voltage-dependent manner, strongly suggesting that tacrine acts as an open
      channel blocker. Second, tacrine produced a new class of closings whose duration
      increased with increasing tacrine concentration. Concentration dependence of
      closed-times is not predicted by sequential models of channel block, suggesting
      that tacrine blocks the nAChR by an unusual mechanism. To probe tacrine's
      mechanism of action we fitted a series of kinetic models to our data using
      maximum likelihood techniques. Models incorporating two tacrine binding sites in
      the open receptor channel gave dramatically improved fits to our data compared
      with the classic sequential model, which contains one site. Improved fits
      relative to the sequential model were also obtained with schemes incorporating a
      binding site in the closed channel, but only if it is assumed that the channel
      cannot gate with tacrine bound. Overall, the best description of our data was
      obtained with a model that combined two binding sites in the open channel with a
      single site in the closed state of the receptor.

PMID- 12198093
TI  - The effects of polarizing current on nerve terminal impulses recorded from
      polymodal and cold receptors in the guinea-pig cornea.
AB  - It was reported recently that action potentials actively invade the sensory nerve
      terminals of corneal polymodal receptors, whereas corneal cold receptor nerve
      terminals are passively invaded (Brock, J.A., S. Pianova, and C. Belmonte. 2001.
      J. Physiol. 533:493-501). The present study investigated whether this functional
      difference between these two types of receptor was due to an absence of voltage
      activated Na(+) conductances in cold receptor nerve terminals. To address this
      question, the study examined the effects of polarizing current on the
      configuration of nerve terminal impulses recorded extracellularly from single
      polymodal and cold receptors in guinea-pig cornea isolated in vitro. Polarizing
      currents were applied through the recording electrode. In both receptor types,
      hyperpolarizing current (+ve) increased the negative amplitude of nerve terminal
      impulses. In contrast, depolarizing current (-ve) was without effect on polymodal
      receptor nerve terminal impulses but increased the positive amplitude of cold
      receptor nerve terminal impulses. The hyperpolarization-induced increase in the
      negative amplitude of nerve terminal impulses represents a net increase in inward
      current. In both types of receptor, this increase in inward current was reduced
      by local application of low Na(+) solution and blocked by lidocaine (10 mM). In
      addition, tetrodotoxin (1 microM) slowed but did not reduce the hyperpolarization
      induced increase in the negative amplitude of polymodal and cold nerve terminal
      impulses. The depolarization-induced increase in the positive amplitude of cold
      receptor nerve terminal impulses represents a net increase in outward current.
      This change was reduced both by lidocaine (10 mM) and the combined application of
      tetraethylammomium (20 mM) and 4-aminopyridine (1 mM). The interpretation is that
      both polymodal and cold receptor nerve terminals possess high densities of
      tetrodotoxin-resistant Na(+) channels. This finding suggests that in cold
      receptors, under normal conditions, the Na(+) conductances are rendered inactive
      because the nerve terminal region is relatively depolarized.

PMID- 12198094
TI  - Regulation of murine airway surface liquid volume by CFTR and Ca2+-activated Cl-
      conductances.
AB  - Two Cl(-) conductances have been described in the apical membrane of both human
      and murine proximal airway epithelia that are thought to play predominant roles
      in airway hydration: (1) CFTR, which is cAMP regulated and (2) the Ca(2+)
      activated Cl(-) conductance (CaCC) whose molecular identity is uncertain. In
      addition to second messenger regulation, cross talk between these two channels
      may also exist and, whereas CFTR is absent or defective in cystic fibrosis (CF)
      airways, CaCC is preserved, and may even be up-regulated. Increased CaCC activity
      in CF airways is controversial. Hence, we have investigated the effects of CFTR
      on CaCC activity and have also assessed the relative contributions of these two
      conductances to airway surface liquid (ASL) height (volume) in murine tracheal
      epithelia. We find that CaCC is up-regulated in intact murine CF tracheal
      epithelia, which leads to an increase in UTP-mediated Cl(-)/volume secretion.
      This up-regulation is dependent on cell polarity and is lost in nonpolarized
      epithelia. We find no role for an increased electrical driving force in CaCC up
      regulation but do find an increased Ca(2+) signal in response to mucosal
      nucleotides that may contribute to the increased Cl(-)/volume secretion seen in
      intact epithelia. CFTR plays a critical role in maintaining ASL height under
      basal conditions and accordingly, ASL height is reduced in CF epithelia. In
      contrast, CaCC does not appear to significantly affect basal ASL height, but does
      appear to be important in regulating ASL height in response to released agonists
      (e.g., mucosal nucleotides). We conclude that both CaCC and the Ca(2+) signal are
      increased in CF airway epithelia, and that they contribute to acute but not basal
      regulation of ASL height.

PMID- 12198095
TI  - Movement and crevices around a sodium channel S3 segment.
AB  - Voltage sensing is due mainly to the movement of positively charged S4 segments
      through the membrane electric field during changes of membrane potential. The
      roles of other transmembrane segments are under study. The S3 segment of domain 4
      (D4/S3) in the sodium channel Na(v)1.4 carries two negatively charged residues
      and has been implicated in voltage-dependent gating. We substituted cysteines
      into nine putative "high impact" sites along the complete length of D4/S3 and
      evaluated their accessibilities to extracellular sulfhydryl reagents. Only the
      four outermost substituted cysteines (L1433C, L1431C, G1430C, and S1427C) are
      accessible to extracellular sulfhydryl reagents. We measured the voltage
      dependent modification rates of the two cysteines situated at the extreme ends of
      this accessible region, L1433C and S1427C. Independent of the charge on the
      sulfhydryl reagents, depolarization increases the reactivity of both of these
      residues. Thus, the direction of the voltage dependence is opposite to that
      expected for a negatively charged voltage sensor, namely an inward translational
      movement in response to depolarization. Intrinsic electrostatic potentials were
      probed by charged sulfhydryl reagents and were either negative or positive,
      respectively, near L1433C and S1427C. The magnitude of the electrostatic
      potential near S1427C decreases with depolarization, suggesting that the
      extracellular crevice next to it widens during depolarization. S1427C experiences
      44% of the electric field, as probed by charged cysteine reagents. To further
      explore movements around D4/S3, we labeled cysteines with the photoactivatable
      cross-linking reagent benzophenone-4-carboxamidocysteine methanethiosulfonate and
      examined the effects of UV irradiation on channel gating. After labeling with
      this reagent, all accessible cysteine mutants show altered gating upon brief UV
      irradiation. In each case, the apparent insertion efficiency of the
      photoactivated benzophenone increases with depolarization, indicating voltage
      dependent movement near the extracellular end of D4/S3.

PMID- 12198097
TI  - Health-related social control within older adults' relationships.
AB  - This study examined the size and composition of older adults' social control
      networks and investigated behavioral and affective responses to the experience of
      social control. Social control in the health domain refers to regulatory attempts
      by others (direct), and feelings of obligation and responsibility to others
      (indirect), that encourage engagement in a healthy lifestyle. Participants were
      181 adults aged 65-80 years who completed a mail survey. On average, older adults
      reported having 3-5 people in their social network who exerted a positive
      influence on their health behaviors, with the size and composition of this
      network varying somewhat by marital and parental statuses. Social control was
      associated with both positive and negative behavioral and affective responses,
      depending on both the type of social control (direct vs indirect) and level of
      relationship satisfaction. Results indicate the importance of better
      understanding the conditions under which social relationships have beneficial
      versus detrimental effects on the well-being of older adults.

PMID- 12198096
TI  - The role of NH2-terminal positive charges in the activity of inward rectifier
      KATP channels.
AB  - Approximately half of the NH(2) terminus of inward rectifier (Kir) channels can
      be deleted without significant change in channel function, but activity is lost
      when more than approximately 30 conserved residues before the first membrane
      spanning domain (M1) are removed. Systematic replacement of the positive charges
      in the NH(2) terminus of Kir6.2 with alanine reveals several residues that affect
      channel function when neutralized. Certain mutations (R4A, R5A, R16A, R27A, R39A,
      K47A, R50A, R54A, K67A) change open probability, whereas an overlapping set of
      mutants (R16A, R27A, K39A, K47A, R50A, R54A, K67A) change ATP sensitivity.
      Further analysis of the latter set differentiates mutations that alter ATP
      sensitivity as a consequence of altered open state stability (R16A, K39A, K67A)
      from those that may affect ATP binding directly (K47A, R50A, R54A). The data help
      to define the structural determinants of Kir channel function, and suggest
      possible structural motifs within the NH(2) terminus, as well as the relationship
      of the NH(2) terminus with the extended cytoplasmic COOH terminus of the channel.

PMID- 12198098
TI  - Ethnic variation in the impact of negative affect and emotion inhibition on the
      health of older adults.
AB  - The relations between patterns of emotional experience, emotion inhibition, and
      physical health have been little studied in older adults or ethnically diverse
      samples. Testing hypotheses derived from work on younger adults, the authors
      examined the relations between negative affect and emotion inhibition and that of
      illness (hypertension, respiratory disease, arthritis, and sleep disorder) in a
      sample (N = 1,118) of community-dwelling older adults from four ethnic groups:
      U.S.-born African Americans, African Caribbeans, U.S.-born European Americans,
      and Eastern European immigrants. Participants completed measures of stress,
      lifestyle risk factors, health, social support, trait negative emotion, and
      emotion inhibition. As expected, the interaction of ethnicity with emotion
      inhibition, and, to a lesser extent, negative affect, was significantly related
      to illness, even when other known risk factors were controlled for. However, the
      relations among these variables were complex, and the patterns did not hold for
      all types of illness or operate in the same direction across ethnic groups.
      Implications for emotion-health relationships in ethnically diverse samples are
      discussed.

PMID- 12198099
TI  - Longitudinal benefit of positive self-perceptions of aging on functional health.
AB  - We examined whether those with more positive self-perceptions of aging (older
      individuals' beliefs about their own aging) report better functional health over
      an 18-year period than do those with more negative self-perceptions of aging. We
      found that those with more positive self-perceptions of aging in 1975 reported
      better functional health from 1977 to 1995, when we controlled for baseline
      measures of functional health, self-rated health, age, gender, race, and
      socioeconomic status. We also demonstrated that perceived control partially
      mediates the relationship between self-perceptions of aging and functioning. The
      sample consisted of 433 participants in the Ohio Longitudinal Study of Aging and
      Retirement, a community-based study of individuals aged 50 and older, who were
      interviewed in 6 waves. Our study suggests that the way in which individuals view
      their own aging affects their functional health.

PMID- 12198100
TI  - Longitudinal predictors of proactive goals and activity participation at age 80.
AB  - This study investigated longitudinal predictors of proactive goals and activity
      participation at age 80 among members of the Terman Study of the Gifted. The
      participants were 242 individuals between the ages of 75 and 84 (M = 79.53) who
      responded to questionnaires in 1992, 1972, and 1950. Proactive goals included
      goals for involvement and achievement. Activity participation included
      intellectual, cultural, and social service activities. LISREL 8 was used to test
      an integrative longitudinal latent variable model of the associations among the
      variables. The results showed that purposiveness at age 40 predicted proactive
      goals at age 80 indirectly through satisfaction with cultural life and service to
      society measured at age 60. Satisfaction with culture and service at age 60 was
      related to activity participation at age 80 through proactive goals. Women rated
      proactive goals as more important to them and indicated greater participation in
      the activities in this study than did men, but the structural equation model was
      invariant across the two groups. The results are discussed in terms of
      contemporary research and theory concerning the self-concept and life span
      development.

PMID- 12198101
TI  - The adaptiveness of selection, optimization, and compensation as strategies of
      life management: evidence from a preference study on proverbs.
AB  - Proverbs were used to examine whether laypeople's conceptions of or preferences
      for life-management strategies are consistent with the model of selection,
      optimization, and compensation (SOC model). The SOC model posits that there are
      three fundamental processes of life management: selection, optimization, and
      compensation. In two studies (N = 64; N = 131), young (19-32 years) and older
      adults (59-85 years) were asked to match proverbs to sentence stems indicative of
      life-management situations. Of the proverbs, half reflected one component of SOC
      and half alternative, non-SOC life-management strategies. SOC-related and
      alternative proverbs were matched on familiarity, understandability, and
      meaningfulness. Two main results were obtained: Young and older adults chose
      proverbs reflecting SOC (a) more frequently and (b) faster than alternative
      proverbs. Study 3 (N = 60, 19-32 year-old participants) ruled out that these
      results were due to an artifact resulting from a stronger, purely semantic
      relationship of the specific sentence stems with the SOC-related proverbs.
      Studies 4 (N = 48 younger and older adults) and 5 (N = 20 younger adults) were
      conducted to test discriminant validity. In contrast with tasks involving long
      term goal orientation and success, there were no preferences for SOC-related
      proverbs for life contexts involving relaxation or leisure. Taken together,
      results of these studies indicate that individuals, when asked to choose between
      alternative proverbs characterizing ways of managing life, prefer SOC-related
      proverbs.

PMID- 12198102
TI  - Disconfirmation of person expectations by older and younger adults: implications
      for social vigilance.
AB  - The research examined whether age-related cognitive declines affect performance
      when people form impressions of others. The results from Experiment 1 showed that
      young and old participants who held positive expectancies about an individual
      spent more time processing and had better memory for information that was
      inconsistent rather than consistent with their expectancies. But participants who
      held negative expectancies tended to focus on information that was consistent
      rather than inconsistent with their expectancies. In Experiment 2 the task was
      made more demanding by limiting the amount of time participants had to form their
      impressions. Under these conditions, older participants who had positive
      expectations showed deficits in memory for negative information compared with
      young participants. As expected, both groups performed similarly when they held
      negative expectancies for the target. The results suggest that although both
      older and younger adults process social information similarly under self-paced
      conditions, older adults may be at a disadvantage processing negative information
      about positively characterized individuals when the context in which impression
      formation occurs is cognitively demanding.

PMID- 12198103
TI  - Psychological well-being of Black and White grandmothers raising grandchildren:
      examination of a two-factor model.
AB  - A theoretical model predicting the positive and negative affect of caregiving
      grandmothers was tested with a sample of 867 grandmothers caring for a grandchild
      in households that did not include either of the grandchild's parents. Results
      confirm that the principles guiding a two-factor model of psychological well
      being operate at the level of subjective role appraisals. Unique predictors of
      positive and negative affect as well as unique predictors of caregiving
      satisfaction and burden were identified. The stability of the model for Black and
      White grandmothers highlights the similarity of the experience across race.

PMID- 12198104
TI  - Behavioral change in persons with dementia: relationships with mental and
      physical health of caregivers.
AB  - The purpose of this study was to examine the effects that changes in behavioral
      and psychological symptoms of dementia of persons with Alzheimer's disease have
      on their caregivers' mental health and physical health. The research design was a
      prospective, longitudinal follow-up study conducted in a major medical center and
      in participants' homes. Longitudinal analysis linking change in behavior to
      caregiver outcomes was based on 64 cases. Care recipients were assessed at the
      time of diagnosis with the Mini-Mental State Examination (MMSE). To provide
      information on the care recipient's behaviors, caregivers participated in an
      interview with the Modified Neuropsychiatric Inventory at diagnosis and at follow
      up. Caregivers also completed a battery of established instruments to measure
      stress appraisal, mental health, and perceptions of their physical health at
      follow-up. Results showed that increases in problem behaviors among persons
      living with dementia, along with residence status, were significant predictors of
      caregivers' mental health and also their physical health. However, these
      relationships were mediated through stress appraisal. Variables such as MMSE
      score of the person with dementia, number of years caregiving, relationship
      status, and education level were not significant predictors of caregivers' health
      when behavior change was in the model.

PMID- 12198105
TI  - Timed-event sequential analysis of agitation in nursing home residents during
      personal care interactions with nursing assistants.
AB  - Computer-assisted behavioral observation data were collected from 66 nursing home
      residents while they received assistance during personal care routines from a
      certified nursing assistant (CNA). Data were collected both before and after a
      comprehensive behavior-management and communication-skills training program was
      delivered to the nursing staff. A total of 30 residents showed 6 or more episodes
      of disruptive vocalization or other forms of agitation during baseline
      observations, and timed-event sequential analysis methods were used to test
      whether certain CNA behaviors either elicited or prevented onsets of agitation in
      these 30 residents. Simple verbal prompts used by CNAs during personal care
      routines before staff training were found to elicit agitation onset ( p =.03),
      whereas positive statements to the resident were found to reduce the likelihood
      of agitation onset (p =.02). In a previous analysis of the effects of staff
      training, we found that rates of resident agitation were significantly lower
      after training compared with baseline and that CNAs increased their rates of
      positive statements to residents. In the present study, timed-event sequential
      analyses indicated that the verbal prompts used by CNAs during personal care
      routines were no longer associated with an increased rate of resident agitation
      after staff training among the 20 residents who showed 6 or more episodes of
      agitation both before and after staff training. These findings suggest that the
      staff training program improved the quality of CNA verbal prompts. The sequential
      analysis of observational data provides an important method for studying
      interpersonal interactions, including those of nursing home residents and the
      nursing staff who care for them.

PMID- 12198106
TI  - A comprehensive strategy for developing closed-ended survey items for use in
      studies of older adults.
AB  - OBJECTIVE: The purpose of this study is to describe the development and
      implementation of a nine-step strategy for devising closed-ended survey questions
      that assess religion in late life. The intent was to illustrate one way in which
      qualitative and quantitative methods could be combined in the same study.
      METHODS: The following methods and procedures were developed to create closed
      ended questions: Focus groups, in-depth interviews, input from ongoing
      quantitative studies, input from an expert panel, cognitive interviews, a
      quantitative pretest, a nationwide random probability sample of elderly people,
      and rigorous empirical psychometric testing. Three hundred ninety-nine older
      people took part in the first seven steps, and 1,500 elders participated in the
      nationwide survey. RESULTS: Approximately 175 closed-ended survey items were
      developed assessing 14 different major dimensions of religion. In the process,
      practical solutions to a number of problems encountered in implementing the nine
      step strategy are discussed. DISCUSSION: The item development strategy may serve
      as a template that can be used to improve the quality of closed-ended survey
      items that assess a wide range of topics in social gerontology.

PMID- 12198107
TI  - Impact of differential item functioning on age and gender differences in
      functional disability.
AB  - OBJECTIVES: Estimates of group differences in functional disability may be biased
      if items exhibit differential item functioning (DIF). For a given item, DIF
      exists if persons in different groups do not have the same probability of
      responding, given their level of disability. This study examines the extent to
      which DIF affects estimates of age and gender group differences in disability
      severity among adults with some functional disability. METHODS: Data came from
      the 1994/1995 National Health Interview Survey Disability Supplement. Analyses
      focused on 5,750 adult respondents who received help or supervision with at least
      one of 11 activities of daily living/instrumental activities of daily living
      tasks. We estimated gender and age group (18-39, 40-69, and 70+) differences in
      disability, using multiple-indicator/multiple-cause models, which treat
      functional disability as a latent trait. RESULTS: Nine items manifested
      significant DIF by age or gender; DIF was especially large for "shopping" and
      "money management." Without adjusting for DIF, middle-aged persons were less
      disabled than elderly men, and women were less disabled than men among nonelderly
      persons. After adjusting for DIF, middle-aged persons did not differ from elderly
      persons, and gender differences within age groups were not significant.
      DISCUSSION: Comparisons of disability across sociodemographic groups need to take
      DIF into account. Future research should examine the causes of DIF and develop
      alternative question wordings that reduce DIF effects.

PMID- 12198108
TI  - The effect of older people's economic resources on care home entry under the
      United Kingdom's long-term care financing system.
AB  - OBJECTIVE: To determine how older people's economic resources affect their
      likelihood of care home entry in the United Kingdom. METHODS: In 1988, income,
      home ownership, and health data were collected for 1,425 people aged 75+.
      Participants received up to five subsequent health assessments before the study
      endpoint (1999), in which care home entry was also recorded. Care home entry was
      identified from death certificates for those who died. Using proportional hazards
      regression, the effect of home ownership and income on the risk of care home
      entry was estimated, controlling for predisposing, enabling, and need factors,
      and health service utilization. RESULTS: Age, living alone, activities of daily
      living restriction, cognitive impairment, poor/fair self-perceived health, and
      contact with services increased the risk of care home entry. Home ownership
      decreased it. Gender was not a significant predictor of care home entry once
      other factors were controlled for, and no significant effect was found for
      income. DISCUSSION: UK public authorities can require older home owners to use
      the value of their homes to pay for institutional but not community-based care,
      thus producing a financial incentive to place home owners in institutional
      settings. However, we find that home ownership reduces the likelihood of care
      home entry, suggesting that other factors dominate the decision process.

PMID- 12198109
TI  - Old age mortality in Japan: does the socioeconomic gradient interact with gender
      and age?
AB  - OBJECTIVES: There is limited knowledge concerning how the effects of
      socioeconomic status (SES) on mortality interact with gender and age. In
      addition, current studies are largely based on data from the Western nations. The
      validity of prior observations needs to be further evaluated. This research
      examines socioeconomic inequalities in old age mortality in Japan, with a special
      emphasis on how inequalities interact with gender and age. METHODS: Data came
      from a 5-wave panel study of a national probability sample of 2,200 elderly
      Japanese conducted between 1987 and 1999. Hazard rate models involving time
      varying covariates were used to ascertain the direct and indirect effects of SES.
      In addition, interaction effects involving SES variables with age and gender were
      evaluated. RESULTS: In contrast to prior findings from the Western developed
      nations, there is an educational crossover effect on mortality among older men,
      in that, at advanced age, those with less education live longer than those with
      higher education. On the other hand, there is some evidence that educational
      differences in the risk of dying tend to converge in the 70-79 age group. More
      interestingly, there is a crossover in the effect of education among the 80 and
      older age group. DISCUSSION: The observation that educational crossover exists
      only among elderly men may be because of gender and SES differences in causes of
      death, morbidity, and health behavior. On the other hand, possible explanations
      for age differences in the educational crossover include selective survival and
      cohort effects.

PMID- 12198110
TI  - Social factors and mortality in the old-old in Israel: the CALAS study.
AB  - OBJECTIVES: Using a theoretical framework that divided social factors measures
      into structure, function, and social engagement, this study determined those
      aspects of social networks most significantly associated with 8-year, all-cause
      mortality among the old-old in Israel. METHODS: Jews (n = 1,340) aged 75-94
      living in Israel on January 1, 1989, were randomly selected from the National
      Population Register; stratified by age, sex, and place of birth; and interviewed
      in person. Mortality was determined according to the National Death Registry
      (December 1997). RESULTS: After controlling for sociodemographics and measures of
      health, cognitive status, depressive symptoms, and physical function, the
      measures of social engagement that explicitly involved others were associated
      with a lower risk of mortality. No measure of the function of the social network
      was associated with risk of mortality. Living in the community without a spouse
      and with a child and living in an institution were significantly associated with
      a higher risk of mortality. DISCUSSION: The finding that participating in
      activities with people outside of the immediate family is associated with a lower
      risk of death has practical implications for helping the aging population and
      their families in their decision-making process. Lack of support for the
      hypothesis that those with more social support would show reduced risk of
      mortality may indicate that the positive effect of perceiving support and the
      negative effect of needing support may cancel each other out and result in no
      perceived effect. In this population, the association between socioeconomic
      status (SES) and the risk of mortality seems to be expressed through the living
      arrangements, with the sick and frail, both in institutions (higher SES) and in
      the community with a child or other (lower SES), having a higher risk of
      mortality. These findings are consistent with the use of children as a substitute
      for institutionalization, and imply that at least some cohabitation was the
      caretaking solution for the noninstitutionalized old-old who were of low SES,
      frail, and close to death.

PMID- 12198111
TI  - Methionine 35 oxidation reduces fibril assembly of the amyloid abeta-(1-42)
      peptide of Alzheimer's disease.
AB  - The major component of amyloid plaques in Alzheimer's disease (AD) is Abeta, a
      small peptide that has high propensity to assemble as aggregated beta-sheet
      structures. Using three well established techniques for studying amyloid
      structure, namely circular dichroism, thioflavin-T fluorescence, and atomic force
      microscopy, we demonstrate that oxidation of the Met-35 side chain to a
      methionine sulfoxide (Met-35(ox)) significantly hinders the rate of fibril
      formation for the 42-residue Abeta-(1-42) at physiological pH. Met-35(ox) also
      alters the characteristic Abeta fibril morphology and prevents formation of the
      protofibril, which is a key intermediate in beta-amyloidosis and the associated
      neurotoxicity. The implications of these results for the biological function and
      role of Abeta with oxidative stress in AD are discussed.

PMID- 12198112
TI  - PEN-2 is an integral component of the gamma-secretase complex required for
      coordinated expression of presenilin and nicastrin.
AB  - The Alzheimer disease-associated presenilin (PS) proteins apparently provide the
      active site of gamma-secretase, an unusual intramembrane-cleaving aspartyl
      protease. PSs principally occur as high molecular weight protein complexes that
      contain nicastrin (Nct) and additional so far unidentified components. Recently,
      PEN-2 has been implicated in gamma-secretase function. Here we identify PEN-2 as
      a critical component of PS1/gamma-secretase and PS2/gamma-secretase complexes.
      Strikingly, in the absence of PS1 and PS1/PS2, PEN-2 levels are strongly reduced.
      Similarly, PEN-2 levels are reduced upon RNA interference-mediated down
      regulation of Nct. On the other side, down-regulation of PEN-2 by RNA
      interference is associated with reduced PS levels, impaired Nct maturation, and
      deficient gamma-secretase complex formation. We conclude that PEN-2 is an
      integral gamma-secretase complex component and that gamma-secretase complex
      components are expressed in a coordinated manner.

PMID- 12198113
TI  - Regulation of DNA methylation in human breast cancer. Effect on the urokinase
      type plasminogen activator gene production and tumor invasion.
AB  - Urokinase-type plasminogen activator (uPA) is a member of the serine protease
      family and can break down various components of the extracellular matrix to
      promote growth, invasion, and metastasis of several malignancies including breast
      cancer. In the current study we examined the role that the DNA methylation
      machinery might be playing in regulating differential uPA gene expression in
      breast cancer cell lines. uPA mRNA is expressed in the highly invasive, hormone
      insensitive human breast cancer cell line MDA-MB-231 but not in hormone
      responsive cell line MCF-7. Using methylation-sensitive PCR, we show that 90% of
      CpG dinucleotides in the uPA promoter are methylated in MCF-7 cells, whereas
      fully demethylated CpGs were detected in MDA-MB-231 cells. uPA promoter activity,
      which is directly regulated by the Ets-1 transcription factor, is inhibited by
      methylation as determined by uPA promoter-luciferase reporter assays. We then
      tested whether the state of expression and methylation of the uPA promoter
      correlates with the global level of DNA methyltransferase and demethylase
      activities in these cell lines. We show that maintenance DNA methyltransferase
      activity is significantly higher in MCF-7 cells than in MDA-MB-231 cells, whereas
      demethylase activity is higher in MDA-MB-231 cells. We suggest that the
      combination of increased DNA methyltransferase activity with reduced demethylase
      activity contributes to the methylation and silencing of uPA expression in MCF-7
      cells. The converse is true in MDA-MB-231 cells, which represents a late stage
      highly invasive breast cancer. The histone deacetylase inhibitor, Trichostatin A,
      induces the expression of the uPA gene in MDA-MB-231 cells but not in MCF-7
      cells. This supports the hypothesis that DNA methylation is the dominant
      mechanism involved in the silencing of uPA gene expression. Taken together, these
      results provide insight into the mechanism regulating the transcription of the
      uPA gene in the complex multistep process of breast cancer progression.

PMID- 12198114
TI  - Constitutively active NFkappa B is required for the survival of S-type
      neuroblastoma.
AB  - The NFkappaB transcription factors can both promote cell survival and induce
      apoptosis depending on cell type and context. Neuroblastoma (NB) cells display
      two predominant culture phenotypes identified as N- and S-types. Malignant S-type
      cells express neither high levels of MYCN nor Bcl-2, suggesting that other
      survival mechanisms are important. We characterized NFkappaB activity in S-type
      cells and determined its role in their survival. S-type lines (SH-EP1 and SK-N
      AS) were treated with pyrrolidine dithiocarbamate (PDTC), a NFkappaB inhibitor,
      or l-1-tosylamido-2-phenylethyl chloromethyl ketone (TPCK), a serine protease
      inhibitor that blocks IkappaBalpha degradation. Both agents induced cell death,
      suggesting that constitutive NFkappaB activity is required for survival. The
      transient expression of a super-repressor IkappaBalpha mutant killed S-type
      cells. The inhibition of NFkappaB produced an apoptotic response characterized by
      the collapse of the mitochondrial transmembrane electrochemical gradient, caspase
      9 activation, and apoptotic DNA changes. Constitutive NFkappaB DNA binding
      activity specifically involving p65 and p50 was demonstrated in S- but not N-type
      cells by electromobility supershift and gene reporter assays. This study
      demonstrates a role for NFkappaB in the survival of S-type NB tumor cells and
      suggests that NFkappaB activity and function differ according to NB tumor cell
      phenotype.

PMID- 12198115
TI  - Differences in apparent pore sizes of low and high voltage-activated Ca2+
      channels.
AB  - Pore size is of considerable interest in voltage-gated Ca(2+) channels because
      they exemplify a fundamental ability of certain ion channels: to display large
      pore diameter, but also great selectivity for their ion of choice. We determined
      the pore size of several voltage-dependent Ca(2+) channels of known molecular
      composition with large organic cations as probes. T-type channels supported by
      the Ca(V)3.1, Ca(V)3.2, and Ca(V)3.3 subunits; L-type channels encoded by the
      Ca(V)1.2, beta(1), and alpha(2)delta(1) subunits; and R-type channels encoded by
      the Ca(V)2.3 and beta(3) subunits were each studied using a Xenopus oocyte
      expression system. The weak permeabilities to organic cations were resolved by
      looking at inward tails generated upon repolarization after a large depolarizing
      pulse. Large inward NH(4)(+) currents and sizable methylammonium and
      dimethylammonium currents were observed in all of the channels tested, whereas
      trimethylammonium permeated only through L- and R-type channels, and
      tetramethylammonium currents were observed only in L-type channels. Thus, our
      experiments revealed an unexpected heterogeneity in pore size among different
      Ca(2+) channels, with L-type channels having the largest pore (effective diameter
      = 6.2 A), T-type channels having the tiniest pore (effective diameter = 5.1 A),
      and R-type channels having a pore size intermediate between these extremes. These
      findings ran counter to first-order expectations for these channels based simply
      on their degree of selectivity among inorganic cations or on the bulkiness of
      their acidic side chains at the locus of selectivity.

PMID- 12198116
TI  - Activation of Gz attenuates Rap1-mediated differentiation of PC12 cells.
AB  - We previously identified a specific activation-dependent interaction between the
      alpha subunit of the heterotrimeric G protein, G(z), and a regulator of Rap1
      signaling, Rap1GAP (Meng, J., Glick, J. L., Polakis, P., and Casey, P. J. (1999)
      J. Biol. Chem. 274, 36663-36669). We now demonstrate that activated forms of
      Galpha(z) are able to recruit Rap1GAP from a cytosolic location to the membrane.
      Using PC12 cells as a model for neuronal differentiation, the influence of G(z)
      activation on Rap1-mediated cell differentiation was examined. Introduction of
      constitutively-activated Galpha(z) into PC12 cells markedly attenuated the
      differentiation process of these cells induced by a cAMP analogue. Treatment of
      PC12 cells expressing wild type Galpha(z) with a specific agonist to the
      alpha(2A)-adrenergic receptor also attenuated cAMP-induced PC12 cell
      differentiation, demonstrating that receptor-mediated activation of G(z) was also
      effective in this regard. Furthermore, activation of G(z) decreased the ability
      of the cAMP analogue to trigger both Rap1 and extracellular-regulated kinase
      (ERK) activation. Differentiation of PC12 cells induced by nerve growth factor
      (NGF) is also thought to be a Rap1-mediated process, and G(z) activation was
      found to attenuate this process as well. Rap1 activation, ERK phosphorylation,
      and PC12 cell differentation induced by NGF treatment were all significantly
      attenuated by either transfection of constitutively activated Galpha(z) or
      receptor-mediated G(z) activation. Based on these findings, a model is proposed
      in which activation of G(z) results in recruitment of Rap1GAP to the membrane
      where it can effectively down-regulate Rap1 signaling. The implications of these
      findings in regard to a possible role for G(z) in neuronal development are
      discussed.

PMID- 12198117
TI  - Sex-specific gene regulation. The Doublesex DM motif is a bipartite DNA-binding
      domain.
AB  - Sex-specific gene expression in Drosophila melanogaster is regulated in part by
      the Doublesex (DSX) transcription factor. Male- and female-specific splicing
      isoforms share a novel DNA-binding domain, designated the DM motif. This domain
      is conserved among a newly recognized family of vertebrate transcription factors
      involved in developmental patterning and sex determination. The DM motif consists
      of an N-terminal zinc module and a disordered C-terminal tail, hypothesized to
      fold on specific DNA binding as a recognition alpha-helix. Truncation of the tail
      does not perturb the structure of the zinc module but impairs DNA binding and DNA
      dependent dimerization. Chemical protein synthesis and alanine scanning
      mutagenesis are employed to test the contributions of 13 side chains to specific
      DNA binding. Selected arginine or lysine residues in the zinc module were
      substituted by norleucine, an isostere that maintains the aliphatic portion of
      the side chain but lacks a positive charge. Arginine or glutamine residues in the
      tail were substituted by alanine. Evidence is obtained that both the zinc module
      and C-terminal tail contribute to a bipartite DNA-binding surface. Conserved
      arginine and glutamine residues in the tail are required for high affinity DNA
      recognition, consistent with its proposed role as a nascent recognition alpha
      helix.

PMID- 12198118
TI  - Two-step membrane binding by Equinatoxin II, a pore-forming toxin from the sea
      anemone, involves an exposed aromatic cluster and a flexible helix.
AB  - Equinatoxin II (EqtII) belongs to a unique family of 20-kDa pore-forming toxins
      from sea anemones. These toxins preferentially bind to membranes containing
      sphingomyelin and create cation-selective pores by oligomerization of 3-4
      monomers. In this work we have studied the binding of EqtII to lipid membranes by
      the use of lipid monolayers and surface plasmon resonance (SPR). The binding is a
      two-step process, separately mediated by two regions of the molecule. An exposed
      aromatic cluster involving tryptophans 112 and 116 mediates the initial
      attachment that is prerequisite for the next step. Steric shielding of the
      aromatic cluster or mutation of Trp-112 and -116 to phenylalanine significantly
      reduces the toxin-lipid interaction. The second step is promoted by the N
      terminal amphiphilic helix, which translocates into the lipid phase. The two
      steps were distinguished by the use of a double cysteine mutant having the N
      terminal helix fixed to the protein core by a disulfide bond. The kinetics of
      membrane binding derived from the SPR experiments could be fitted to a two-stage
      binding model. Finally, by using membrane-embedded quenchers, we showed that
      EqtII does not insert deeply in the membrane. The first step of the EqtII binding
      is reminiscent of the binding of the evolutionarily distant cholesterol-dependant
      cytolysins, which share a similar structural motif in the membrane attachment
      domain.

PMID- 12198119
TI  - Differential cytostatic and apoptotic effects of ecteinascidin-743 in cancer
      cells. Transcription-dependent cell cycle arrest and transcription-independent
      JNK and mitochondrial mediated apoptosis.
AB  - We have found that ecteinascidin-743 (ET-743) inhibited cell proliferation at 1
      10 ng/ml, leading to S and G(2)/M arrest and subsequent apoptosis, and induced
      early apoptosis without previous cell cycle arrest at 10-100 ng/ml in cancer
      cells. ET-743-mediated apoptosis, did not involve Fas/CD95. ET-743 induced c-Jun
      NH(2)-terminal kinase (JNK) and caspase-3 activation, and JNK and caspase
      inhibition prevented ET-743-induced apoptosis. ET-743 failed to promote apoptosis
      in caspase-3-deficient MCF-7 cells, further implicating caspase-3 in its
      proapoptotic action. Overexpression of bcl-2 by gene transfer abrogated ET-743
      induced apoptosis, but cells underwent cell cycle arrest. ET-743 triggered
      cytochrome c release from mitochondria that was inhibited by Bcl-2
      overexpression. Inhibition of transcription or protein synthesis did not prevent
      ET-743-induced apoptosis, but abrogated ET-743-induced cell cycle arrest.
      Microarray analyses revealed changes in the expression of a small number of cell
      cycle-related genes (p21, GADD45A, cyclin G2, MCM5, and histones) that suggested
      their putative involvement in ET-743-induced cell cycle arrest. These data
      indicate that ET-743 is a very potent anticancer drug showing dose-dependent
      cytostatic and proapoptotic effects through activation of two different signaling
      pathways, namely a transcription-dependent pathway leading to cell cycle arrest
      and a transcription-independent route leading to rapid apoptosis that involves
      mitochondria, JNK, and caspase-3.

PMID- 12198120
TI  - Ectopic expression of necdin induces differentiation of mouse neuroblastoma
      cells.
AB  - Necdin is expressed predominantly in postmitotic neurons, and ectopic expression
      of this protein strongly suppresses cell growth. Necdin has been implicated in
      the pathogenesis of Prader-Willi syndrome, a human neurodevelopmental disorder
      associated with genomic imprinting. Here we demonstrate that ectopic expression
      of necdin induces a neuronal phenotype in neuroblastoma cells. Necdin was
      undetectable in mouse neuroblastoma N1E-115 cells under undifferentiated and
      differentiated conditions. N1E-115 cells transfected with necdin cDNA showed
      morphological differentiation such as neurite outgrowth and expression of the
      synaptic marker proteins synaptotagmin and synaptophysin. In addition, Western
      blot analysis of the retinoblastoma protein (Rb) family members Rb, p130, and
      p107 revealed that necdin cDNA transfectants contained an increased level of p130
      and a reduced level of p107, a pattern seen in differentiated G(0) cells. The
      transcription factors E2F1 and E2F4 physically interacted with necdin via their
      carboxyl-terminal transactivation domains, but only E2F1 abrogated necdin-induced
      growth arrest and neurite outgrowth of neuroblastoma cells. Overexpression of
      E2F1 in differentiated N1E-115 cells induced apoptosis, which was antagonized by
      co-expression of necdin. These results suggest that necdin promotes the
      differentiation and survival of neurons through its antagonistic interactions
      with E2F1.

PMID- 12198121
TI  - Loss of pentameric symmetry of C-reactive protein is associated with delayed
      apoptosis of human neutrophils.
AB  - Human neutrophil granulocytes die rapidly, and their survival is contingent upon
      rescue from programmed cell death by signals from the environment. Here we report
      that a novel signal for delaying neutrophil apoptosis is the classic acute phase
      reactant, C-reactive protein (CRP). However, this anti-apoptotic activity is
      expressed only when the cyclic pentameric structure of CRP is lost, resulting in
      formation of modified or monomeric CRP (mCRP), which may be formed in inflamed
      tissues. By contrast, native pentameric CRP and CRP peptides 77-82, 174-185, and
      201-206 failed to affect neutrophil apoptosis. The apoptosis delaying action of
      mCRP was markedly attenuated by an antibody against the low affinity IgG immune
      complex receptor (CD16) but not by an anti-CD32 antibody. mCRP evoked a transient
      concurrent activation of the extracellular signal-regulated kinase (ERK) and
      phosphatidylinositol 3-kinase/Akt signaling pathways, leading to inhibition of
      caspase-3 and consequently to delaying apoptosis. Consistently, pharmacological
      inhibition of either ERK or Akt reversed the anti-apoptotic action of mCRP;
      however, they did not produce additive inhibition. Thus, mCRP, but not pentameric
      CRP or peptides derived from CRP, promotes neutrophil survival and may therefore
      contribute to amplification of the inflammatory response.

PMID- 12198122
TI  - Constitutive activation and transgenic evaluation of the function of an
      arabidopsis PKS protein kinase.
AB  - A novel family of SOS2 (salt overly sensitive 2)-like protein kinase genes
      (designated PKSes) have been recently identified in Arabidopsis. The biochemical
      characteristics as well as in vivo roles of most of the PKSes are unclear at
      present. In this work, we isolated and characterized one of the PKSes, PKS18.
      PKS18 was expressed in leaves of mature Arabidopsis plants. The glutathione S
      transferase (GST)-PKS18 fusion protein was inactive by itself in substrate
      phosphorylation. An activation loop Thr(169) to Asp mutation, however, highly
      activated this kinase in vitro (designated PKS18T/D). Kinase activity of the
      PKS18T/D preferred Mn(2+) to Mg(2+). The activated kinase showed a substrate
      specificity, and high catalytic efficiency for a peptide substrate p3 and for
      ATP. Interestingly, PKS18T/D transgenic plants were hypersensitive to the
      phytohormone abscisic acid (ABA) in seed germination and seedling growth, whereas
      silencing the kinase gene by RNA interference (RNAi) conferred ABA-insensitivity,
      indicating the involvement of PKS18 in plant ABA signaling.

PMID- 12198123
TI  - Insertion and assembly of human tom7 into the preprotein translocase complex of
      the outer mitochondrial membrane.
AB  - Tom7 is a component of the translocase of the outer mitochondrial membrane (TOM)
      and assembles into a general import pore complex that translocates preproteins
      into mitochondria. We have identified the human Tom7 homolog and characterized
      its import and assembly into the mammalian TOM complex. Tom7 is imported into
      mitochondria in a nucleotide-independent manner and is anchored to the outer
      membrane with its C terminus facing the intermembrane space. Unlike studies in
      fungi, we found that human Tom7 assembles into an approximately 120-kDa import
      intermediate in HeLa cell mitochondria. To detect subunits within this complex,
      we employed a novel supershift analysis whereby mitochondria containing newly
      imported Tom7 were incubated with antibodies specific for individual TOM
      components prior to separation by blue native electrophoresis. We found that the
      120-kDa complex contains Tom40 and lacks receptor components. This intermediate
      can be chased to the stable approximately 380-kDa mammalian TOM complex that
      additionally contains Tom22. Overexpression of Tom22 in HeLa cells results in the
      rapid assembly of Tom7 into the 380-kDa complex indicating that Tom22 is rate
      limiting for TOM complex formation. These results indicate that the levels of
      Tom22 within mitochondria dictate the assembly of TOM complexes and hence may
      regulate its biogenesis.

PMID- 12198124
TI  - Alternative splicing and interaction with di- and polyvalent cations control the
      dynamic range of acid-sensing ion channel 1 (ASIC1).
AB  - Homomeric acid-sensing ion channel 1 (ASIC1) can be activated by extracellular
      H(+) in the physiological pH range and may, therefore, contribute to
      neurotransmission and peripheral pain perception. ASIC1a and ASIC1b are
      alternative splice products of the ASIC1 gene. Here we show that both splice
      variants show steady-state inactivation when exposed to slightly decreased pH,
      limiting their operational range. Compared with ASIC1a, steady-state inactivation
      and pH activation of ASIC1b are shifted to more acidic values by 0.25 and 0.7 pH
      units, respectively, extending the dynamic range of ASIC1. Shifts of inactivation
      and activation are intimately linked; only two amino acids in the ectodomain,
      which are exchanged by alternative splicing, control both properties. Moreover,
      we show that extracellular, divalent cations like Ca(2+) and Mg(2+) as well as
      the polyvalent cation spermine shift the steady-state inactivation of ASIC1a and
      ASIC1b to more acidic values. This leads to a potentiation of the channel
      response and is due to a stabilization of the resting state. Our results indicate
      that ASIC1b is an effective sensor of transient H(+) signals during slight
      acidosis and that, in addition to alternative splicing, interaction with di- and
      polyvalent cations extends the dynamic range of ASIC H(+) sensors.

PMID- 12198125
TI  - Proteolytic activation of protein kinase C-epsilon by caspase-mediated processing
      and transduction of antiapoptotic signals.
AB  - Several novel protein kinase C (PKC) isozymes have been identified as substrates
      for caspase-3. We have previously shown that novel PKCepsilon is cleaved during
      apoptosis in MCF-7 cells that lack any functional caspase-3. In the present
      study, we show that in vitro-translated PKCepsilon is processed by human
      recombinant caspase-3, -7, and -9. Tumor necrosis factor-alpha (TNF) triggered
      processing of PKCepsilon to a 43-kDa carboxyl-terminal fragment, and cell
      permeable caspase inhibitors prevented TNF-induced processing of PKCepsilon in
      MCF-7 cells. PKCepsilon was cleaved primarily at the SSPD downward arrow G site
      to generate two fragments with an approximate molecular mass of 43 kDa. It was
      also cleaved at the DDVD downward arrow C site to generate two fragments with
      molecular masses of 52 and 35 kDa. Treatment of MCF-7 cells with TNF resulted in
      the activation of PKCepsilon, and mutation at the SSPD downward arrow G (D383A)
      site inhibited proteolytic activation of PKCepsilon. Overexpression of wild-type
      but not dominant-negative PKCepsilon in MCF-7 cells delayed TNF-induced
      apoptosis, and mutation at the D383A site prevented antiapoptotic activity of
      PKCepsilon. These results suggest that cleavage of PKCepsilon by caspase-7 at the
      SSPD downward arrow G site results in the activation of PKCepsilon. Furthermore,
      activation of PKCepsilon was associated with its antiapoptotic function.

PMID- 12198126
TI  - Structure, stability, and aggregation of paired helical filaments from tau
      protein and FTDP-17 mutants probed by tryptophan scanning mutagenesis.
AB  - By using tryptophan scanning mutagenesis, we observed the kinetics and structure
      of the polymerization of tau into paired helical filaments (PHFs) independently
      of exogenous reporter dyes. The fluorescence exhibits pronounced blue shifts due
      to burial of the residue inside PHFs, depending on Trp position. The effect is
      greatest near the center of the repeat domain, showing that the packing is
      tightest near the beta-structure inducing hexapeptide motifs. The tryptophan
      response allows measurement of PHF stability made by different tau isoforms and
      mutants. Unexpectedly, the stability of PHFs is quite low (denaturation half
      points approximately 1.0 m GdnHCl), implying that incipient aggregation should be
      reversible and that the observed high stability of Alzheimer PHFs is due to other
      factors. The stability increases with the number of repeats and with tau mutants
      promoting beta-structure, arguing for a gain of toxic function in frontotemporal
      dementias. Fluorescence resonance energy transfer (FRET) was used to analyze the
      distances of Tyr(310) to tryptophans in different positions. The degree of FRET
      in the soluble protein was position-dependent, with highest signals within the
      second and third repeats but low or no signals further away. In PHFs most mutants
      showed FRET, indicating that tight packing results from assembly of tau into
      PHFs.

PMID- 12198127
TI  - Benzoate X receptors alpha and beta are pharmacologically distinct and do not
      function as xenobiotic receptors.
AB  - The Xenopus benzoate nuclear hormone receptors, BXRalpha and BXRbeta, share 82%
      identity within their ligand-binding domains and are classified as members of the
      NR1I2 subfamily that includes the mammalian steroid and xenobiotic receptor,
      SXR/PXR. Although alkyl benzoates have been identified as endogenous ligands, the
      exact role of the benzoate receptors in amphibian physiology has not been
      established. In this report, we show that BXRalpha and BXRbeta are
      pharmacologically distinct from each other: BXRalpha is more promiscuous than
      BXRbeta with respect to both ligand specificity and co-activator recruitment.
      BXRalpha can be transactivated by a number of benzoate derivatives including 4
      amino-butylbenzoate (4-ABB), 4-hydroxy-butylbenzoate (4-HBB), 3-hydroxy ethyl
      benzoate (3-HEB), and benzyl benzoate, but only 4-HBB acts as an agonist for both
      receptors. Furthermore, BXRalpha-specific agonists such as 4-ABB, chlorpyrifos,
      and trifluralin act as antagonists on BXRbeta. BXRs are widely distributed in
      adult tissues but do not show any enrichment in liver and intestine, major sites
      of SXR/PXR expression that are critical in xenobiotic metabolism. Neither BXR
      shows the broad specificity toward steroids or xenobiotics exhibited by SXR/PXR.
      Therefore, we conclude that the BXRs are pharmacologically distinct from each
      other and unlikely to serve as xenobiotic sensors.

PMID- 12198128
TI  - Hormonal regulation of cystathionine beta-synthase expression in liver.
AB  - Homocysteine metabolism is altered in diabetic patients. Cystathionine beta
      synthase (CBS), a key enzyme involved in the transsulfuration pathway, which
      irreversibly converts homocysteine to cysteine, catalyzes the condensation of
      serine and homocysteine to cystathionine. Studies in streptozotocin-induced
      diabetic rats have shown that CBS enzyme activity is elevated in the liver but
      not in the kidney, and this effect is reversed by insulin treatment. To determine
      whether these effects resulted from alterations at the level of gene
      transcription, CBS mRNA was measured in diabetic and insulin-treated diabetic
      rats. CBS mRNA levels were found to be markedly higher in streptozotocin-induced
      diabetic rat livers; these were reduced by insulin administration. In H4IIE
      cells, a rat hepatoma cell culture model, glucocorticoids increased the cellular
      levels of CBS enzyme protein and CBS mRNA; insulin inhibited this stimulatory
      effect. Treatment with insulin also decreased CBS levels in HepG2 cells, a human
      hepatoma cell line. Nuclear run-on experiments in the rat cells confirmed that
      stimulation of CBS gene expression by glucocorticoids and the inhibition by
      insulin occurred at the transcriptional level. Transient transfections of HepG2
      cells with a CBS-1b promoter luciferase reporter construct showed that the
      promoter activity was decreased by 70% after insulin treatment. These results
      show that insulin has a direct role in regulating homocysteine metabolism.
      Altered insulin levels in diseases such as diabetes may influence homocysteine
      metabolism by regulating the hepatic transsulfuration pathway.

PMID- 12198129
TI  - Aminoacylation of the N-terminal cysteine is essential for Lol-dependent release
      of lipoproteins from membranes but does not depend on lipoprotein sorting
      signals.
AB  - Lipoproteins are present in a wide variety of bacteria and are anchored to
      membranes through lipids attached to the N-terminal cysteine. The Lol system of
      Escherichia coli mediates the membrane-specific localization of lipoproteins.
      Aspartate at position 2 functions as a Lol avoidance signal and causes the
      retention of lipoproteins in the inner membrane, whereas lipoproteins having
      residues other than aspartate at position 2 are released from the inner membrane
      and localized to the outer membrane by the Lol system.
      Phospholipid:apolipoprotein transacylase, Lnt, catalyzes the last step of
      lipoprotein modification, converting apolipoprotein into mature lipoprotein. To
      reveal the importance of this aminoacylation for the Lol-dependent membrane
      localization, apolipoproteins were prepared by inhibiting lipoprotein maturation.
      Lnt was also purified and used to convert apolipoprotein into mature lipoprotein
      in vitro. The release of these lipoproteins was examined in proteoliposomes. We
      show here that the aminoacylation is essential for the Lol-dependent release of
      lipoproteins from membranes. Furthermore, lipoproteins with aspartate at position
      2 were found to be aminoacylated both in vivo and in vitro, indicating that the
      lipoprotein-sorting signal does not affect lipid modification.

PMID- 12198130
TI  - Phosphorylation of Nrf2 at Ser-40 by protein kinase C regulates antioxidant
      response element-mediated transcription.
AB  - Nrf2, a basic leucine zipper transcription factor, is an essential activator of
      the coordinated transcription of genes encoding antioxidant enzymes and phase II
      detoxifying enzymes through the regulatory sequence termed antioxidant response
      element (ARE). Recently we reported evidence for the involvement of protein
      kinase C (PKC) in phosphorylating Nrf2 and triggering its nuclear translocation
      in response to oxidative stress. We show here that phosphorylation of purified
      rat Nrf2 by the catalytic subunit of PKC was blocked by a synthetic peptide
      mimicking one of the potential PKC sites. Accordingly, Nrf2 bearing a Ser to Ala
      mutation at amino acid 40 (S40A) could not be phosphorylated by PKC. The S40A
      mutation did not affect in vitro binding of Nrf2/MafK to the ARE. However, it
      partially impaired Nrf2 activation of ARE-driven transcription in a reporter gene
      assay when Keap1 was overexpressed. In vitro transcribed/translated Keap1 could
      be coimmunoprecipitated with Nrf2. Phosphorylation of wild-type Nrf2 by PKC
      promoted its dissociation from Keap1, whereas the Nrf2-S40A mutant remained
      associated. These findings together with our prior studies suggest that the PKC
      catalyzed phosphorylation of Nrf2 at Ser-40 is a critical signaling event leading
      to ARE-mediated cellular antioxidant response.

PMID- 12198132
TI  - The phox homology (PX) domain-dependent, 3-phosphoinositide-mediated association
      of sorting nexin-1 with an early sorting endosomal compartment is required for
      its ability to regulate epidermal growth factor receptor degradation.
AB  - Recent studies have shown that phox homology (PX) domains act as phosphoinositide
      binding motifs. The majority of PX domains studied show binding to
      phosphatidylinositol 3-monophosphate (PtdIns(3)P), an association that allows the
      host protein to localize to membranes of the endocytic pathway. One issue,
      however, is whether PX domains may have alternative phosphoinositide binding
      specificities that could target their host protein to distinct subcellular
      compartments or allow their allosteric regulation by phosphoinositides other than
      PtdIns(3)P. It has been reported that the PX domain of sorting nexin 1 (SNX1)
      specifically binds phosphatidylinositol 3,4,5-trisphosphate (PtdIns(3,4,5)P(3))
      (Zhong, Q., Lazar, C. S., Tronchere, H., Sato, T., Meerloo, T., Yeo, M.,
      Songyang, Z., Emr, S. D., and Gill, G. N. (2002) Proc. Natl. Acad. Sci. U. S. A.
      99, 6767-6772). In the present study, we have shown that whereas SNX1 binds
      PtdIns(3,4,5)P(3) in protein:lipid overlay assays, in liposomes-based assays,
      binding is observed to PtdIns(3)P and phosphatidylinositol 3,5-bisphosphate
      (PtdIns(3,5)P(2)) but not to PtdIns(3,4,5)P(3). To address the significance of
      PtdIns(3,4,5)P(3) binding, we examined the subcellular localization of SNX1 under
      conditions in which plasma membrane PtdIns(3,4,5)P(3) levels were significantly
      elevated. Under these conditions, we failed to observe association of SNX1 with
      this membrane. However, consistent with the binding to PtdIns(3)P and
      PtdIns(3,5)P(2) being of more physiological significance was the observation that
      the association of SNX1 with an early endosomal compartment was dependent on a 3
      phosphoinositide-binding PX domain and the presence of PtdIns(3)P on this
      compartment. Finally, we have shown that the PX domain-dependent/early endosomal
      association of SNX1 is important for its ability to regulate the targeting of
      internalized epidermal growth factor receptor for lysosomal degradation.

PMID- 12198131
TI  - Mitochondrial transcription factor A and its downstream targets are up-regulated
      in a rat hepatoma.
AB  - Mitochondrial transcription factor A is a key regulator involved in mitochondrial
      DNA transcription and replication. In a poorly differentiated rat hepatoma,
      Morris hepatoma 3924A, the mRNA and protein levels of this factor were elevated
      about 10- and 11-fold, respectively, relative to the host liver. The mRNA levels
      for the hepatoma cytochrome c oxidase I, II, and NADH dehydrogenase 5, 6, the
      downstream targets of Tfam, were augmented 10-, 8-, 5-, and 3-fold, respectively.
      Interestingly, Tfam was also found in the hepatoma nucleus. The mRNA levels for
      nuclear respiratory factor 1 and 2 (NRF-1 and -2), the proteins that are known to
      interact with specific regulatory elements on human TFAM promoter, were 5- and 3
      fold higher, respectively, in the hepatoma relative to the host liver. Unlike the
      human promoter, the rat Tfam promoter did not form a specific complex with the
      NRF-1 in the liver or hepatoma nuclear extracts, which is consistent with the
      absence of an NRF-1 consensus sequence in the proximal rat promoter. A single
      specific complex formed between the rat promoter and the NRF-2 protein was
      comparable in the two extracts. The DNA binding activity of Sp1 in the hepatoma
      nuclear extract was 4-fold greater than that in the liver extract. In vivo
      genomic footprinting showed occupancy of NRF-2 and Sp1 consensus sites on the
      promoter of rat Tfam gene. Tfam was also up-regulated in other hepatoma cells.
      Together, these results show up-regulation of Tfam in some tumors, particularly
      the liver tumors. Further, the relatively high level of Sp1 binding to the
      promoter in the hepatoma could play a major role in the up-regulation of Tfam in
      these tumor cells.

PMID- 12198133
TI  - Identification and characterization of a cDNA encoding a dolichyl pyrophosphate
      phosphatase located in the endoplasmic reticulum of mammalian cells.
AB  - The CWH8 gene in Saccharomyces cerevisiae has been shown recently (Fernandez, F.,
      Rush, J. S., Toke, D. A., Han, G., Quinn, J. E., Carman, G. M., Choi, J.-Y.,
      Voelker, D. R., Aebi, M., and Waechter, C. J. (2001) J. Biol. Chem. 276, 41455
      41464) to encode a dolichyl pyrophosphate (Dol-P-P) phosphatase associated with
      crude microsomal fractions. Mutations in CWH8 result in the accumulation of Dol-P
      P, deficiency in lipid intermediate synthesis, defective protein N-glycosylation,
      and a reduced growth rate. A cDNA (DOLPP1, GenBank accession number AB030189)
      from mouse brain encoding a homologue of the yeast CWH8 gene is now shown to
      complement the defects in growth and protein N-glycosylation, and to correct the
      accumulation of Dol-P-P in the cwh8Delta yeast mutant. Northern blot analyses
      demonstrate a wide distribution of the DOLPP1 mRNA in mouse tissues.
      Overexpression of Dolpp1p in yeast, COS, and Sf9 cells produces substantial
      increases in Dol-P-P phosphatase activity but not in dolichyl monophosphate or
      phosphatidic acid phosphatase activities in microsomal fractions. Subcellular
      fractionation and immunofluorescence studies localize the enzyme encoded by
      DOLPP1 to the endoplasmic reticulum of COS cells. The results of protease
      sensitivity studies with microsomal vesicles from the lpp1Delta/dpp1Delta yeast
      mutant expressing DOLPP1 are consistent with Dolpp1p having a luminally oriented
      active site. The sequence of the DOLPP1 cDNA predicts a polypeptide with 238
      amino acids, and a new polypeptide corresponding to 27 kDa is observed when
      DOLPP1 is expressed in yeast, COS, and Sf9 cells. This study is the first
      identification and characterization of a cDNA clone encoding an essential
      component of a mammalian lipid pyrophosphate phosphatase that is highly specific
      for Dol-P-P. The specificity, subcellular location, and topological orientation
      of the active site described in the current study strongly support a role for
      Dolpp1p in the recycling of Dol-P-P discharged during protein N-glycosylation
      reactions on the luminal leaflet of the endoplasmic reticulum in mammalian cells.

PMID- 12198134
TI  - Ribosomal proteins at the stalk region modulate functional rRNA structures in the
      GTPase center.
AB  - Replacement of the L10.L7/L12 protein complex and L11 in Escherichia coli
      ribosomes with the respective rat counterparts P0.P1/P2 and eukaryotic L12 causes
      conversion of ribosomal specificity for elongation factors from prokaryotic
      elongation factor (EF)-Tu/EF-G to eukaryotic EF (eEF)-1alpha/eEF-2. Here we have
      investigated the effects of protein replacement on the structure and function of
      two rRNA domains around positions 1070 and 2660 (sarcin/ricin loop) of 23 S rRNA.
      Protein replacement at the 1070 region in E. coli 50 S subunits was demonstrated
      by chemical probing analysis. Binding of rat proteins to the 1070 region caused
      increased accessibility of the 2660 and 1070 regions to ligands for eukaryotic
      ribosomes: the ribotoxin pepocin for the 2660 region (E. coli numbering), anti-28
      S autoantibody for the 1070 region, and eEF-2 for both regions. Moreover, binding
      of the E. coli L10.L7/L12 complex and L11 to the 1070 region was shown to be
      responsible for E. coli ribosomal accessibility to another ribotoxin,
      gypsophilin. Ribosomal proteins at the 1070 region appear to modulate the
      structures and functions of the 2660 and 1070 RNA regions in slightly different
      modes in prokaryotes and eukaryotes.

PMID- 12198135
TI  - An iron-responsive element type II in the 5'-untranslated region of the
      Alzheimer's amyloid precursor protein transcript.
AB  - Iron-responsive elements (IREs) are the RNA stem loops that control cellular iron
      homeostasis by regulating ferritin translation and transferrin receptor mRNA
      stability. We mapped a novel iron-responsive element (IRE-Type II) within the 5'
      untranslated region (5'-UTR) of the Alzheimer's amyloid precursor protein (APP)
      transcript (+51 to +94 from the 5'-cap site). The APP mRNA IRE is located
      immediately upstream of an interleukin-1 responsive acute box domain (+101 to
      +146). APP 5'-UTR conferred translation was selectively down-regulated in
      response to intracellular iron chelation using three separate reporter assays
      (chloramphenicol acetyltransferase, luciferase, and red fluorescent protein
      reflecting an inhibition of APP holoprotein translation in response to iron
      chelation. Iron influx reversed this inhibition. As an internal control to ensure
      specificity, a viral internal ribosome entry sequence was unresponsive to
      intracellular iron chelation with desferrioxamine. Using RNA mobility shift
      assays, the APP 5'-UTRs, encompassing the IRE, bind specifically to recombinant
      iron-regulatory proteins (IRP) and to IRP from neuroblastoma cell lysates. IRP
      binding to the APP 5'-UTR is reduced after treatment of cells with
      desferrioxamine and increased after interleukin-1 stimulation. IRP binding is
      abrogated when APP cRNA probe is mutated in the core IRE domain (Delta4
      bases:Delta83AGAG86). Iron regulation of APP mRNA through the APP 5'-UTR points
      to a role for iron in the metabolism of APP and confirms that this RNA structure
      can be a target for the selection of small molecule drugs, such as
      desferrioxamine (Fe chelator) and clioquinol (Fe, Cu, and Zn chelator), which
      reduce Abeta peptide burden during Alzheimer's disease.

PMID- 12198136
TI  - Diffusion of tricarboxylic acid cycle enzymes in the mitochondrial matrix in
      vivo. Evidence for restricted mobility of a multienzyme complex.
AB  - It has been proposed that enzymes in many metabolic pathways, including the
      tricarboxylic acid cycle in the mitochondrial matrix, are physically associated
      to facilitate substrate channeling and overcome diffusive barriers. We have used
      fluorescence recovery after photobleaching to measure the diffusional mobilities
      of chimeras consisting of green fluorescent protein (GFP) fused to the C terminus
      of four tricarboxylic acid cycle enzymes: malate dehydrogenase, citrate synthase,
      isocitrate dehydrogenase, and succinyl-CoA synthetase. The GFP-enzyme chimeras
      were localized selectively in the mitochondrial matrix in transfected Chinese
      hamster ovary (CHO) and COS7 cells. Laser photobleaching using a 0.7-microm
      diameter spot demonstrated restricted diffusion of the GFP-enzyme chimeras.
      Interestingly, all four chimeras had similar diffusional characteristics,
      approximately 45% of each chimera was mobile and had a diffusion coefficient of 4
      x 10(-8) cm(2)/s. In contrast, unconjugated GFP in the mitochondrial matrix
      (targeted using COX8 leader sequence) diffused freely (nearly 100% mobility) with
      a greater diffusion coefficient of 20 x 10(-8) cm(2)/s. The mobility of the GFP
      enzyme chimeras was insensitive to substrate source, ATP depletion, or inhibition
      of the adenine nucleotide translocase. These results indicate similar mobility
      characteristics of unrelated tricarboxylic acid cycle enzymes having different
      sizes and physical properties, providing biophysical evidence for a diffusible
      multienzyme complex in the mitochondrial matrix.

PMID- 12198137
TI  - Bcl-XL protects BimEL-induced Bax conformational change and cytochrome C release
      independent of interacting with Bax or BimEL.
AB  - The Bcl-2 homology (BH) 3-only pro-apoptotic Bcl-2 family protein Bim plays an
      essential role in the mitochondrial pathway of apoptosis through activation of
      the BH1-3 multidomain protein Bax or Bak. To further understand how the BH3-only
      protein activates Bax, we provide evidence here that BimEL induces Bax
      conformational change and apoptosis through a Bcl-XL-suppressible but
      heterodimerization-independent mechanism. Substitution of the conserved leucine
      residue in the BH3 domain of BimEL for alanine (M1) inhibits the interaction of
      BimEL with Bcl-XL but does not abolish the ability of BimEL to induce Bax
      conformational change and apoptosis. However, removal of the C-terminal
      hydrophobic region from the M1 mutant (M1DeltaC) abolishes its ability to
      activate Bax and to induce apoptosis, although deletion of the C-terminal domain
      (DeltaC) alone has little if any effect on the pro-apoptotic activity of BimEL.
      Subcellular fractionation experiments show that the Bim mutant M1DeltaC is
      localized in the cytosol, indicating that both the C-terminal hydrophobic region
      and the BH3 domain are required for the mitochondrial targeting and pro-apoptotic
      activity of BimEL. Moreover, the Bcl-XL mutant (mt1), which is unable to interact
      with Bax and BimEL, blocks Bax conformational change and cytochrome c release
      induced by BimEL in intact cells and isolated mitochondria. BimEL or Bak-BH3
      peptide induces Bax conformational change in vitro only under the presence of
      mitochondria, and the outer mitochondrial membrane fraction is sufficient for
      induction of Bax conformational change. Interestingly, native Bax is attached
      loosely on the surface of isolated mitochondria, which undergoes conformational
      change and insertion into mitochondrial membrane upon stimulation by BimEL, Bak
      BH3 peptide, or freeze/thaw damage. Taken together, these findings indicate that
      BimEL may activate Bax by damaging the mitochondrial membrane structure directly,
      in addition to its binding and antagonizing Bcl-2/Bcl-XL function.

PMID- 12198138
TI  - Caspase-11 gene expression in response to lipopolysaccharide and interferon-gamma
      requires nuclear factor-kappa B and signal transducer and activator of
      transcription (STAT) 1.
AB  - Murine caspase-11, together with caspase-1, is essential for the production of IL
      1beta in response to lipopolysaccharide (LPS). In most cells, caspase-11 is only
      expressed upon induction with pro-inflammatory stimuli. To understand how caspase
      11 expression is transcriptionally regulated, we isolated the caspase-11 gene
      promoter by genome walking and investigated the mechanisms regulating caspase-11
      gene expression in macrophages that are treated with LPS and interferon-gamma.
      Transient transfections with caspase-11 promoter-luciferase reporter constructs
      and deletion/mutation analysis revealed an essential role for NF-kappaB binding
      in the up-regulation of caspase-11 in response to LPS. In the case of interferon
      gamma stimulation, signal transducer and activator of transcription 1 binding to
      the caspase-11 promoter could be shown to be required for caspase-11 expression.

PMID- 12198139
TI  - Analysis of the Munc18b-syntaxin binding interface. Use of a mutant Munc18b to
      dissect the functions of syntaxins 2 and 3.
AB  - Munc18b is a mammalian Sec1-related protein that is abundant in epithelial cells
      and regulates vesicle transport to the apical plasma membrane. We constructed a
      homology model of Munc18b in complex with syntaxin 3 based on the crystal
      structure of the neuronal Sec1.syntaxin 1A complex. In this model we identified
      all residues in the interface between the two proteins that contribute directly
      to the interaction and mutagenized residues in Munc18b to alter its binding to
      syntaxins 1A, 2, and 3. The syntaxin-binding properties of the mutants were
      tested using an in vitro assay and by a co-immunoprecipitation approach employing
      Munc18b expressed in CHO-K1 cells. Three Munc18b variants, W28S, S42K, and E59K,
      were generated that are defective in binding to all three syntaxins. A fourth
      mutant protein, S48D, shows abolishment of syntaxin 3 interaction but binds
      syntaxin 2 at normal and syntaxin 1A at mildly reduced efficiency. Over
      expression of Munc18b S48D inhibited transport of influenza hemagglutinin to the
      apical surface of Madin-Darby canine kidney II cells, which express syntaxin 2
      abundantly, but not of Caco-2 cells, in which syntaxin 3 is the major apical
      target SNARE (soluble NSF (N-ethylmaleimide sensitive factor) attachment protein
      receptors). This suggests that, although syntaxin 3 is the main target SNARE
      operating in exocytic transport to the apical plasma membrane in certain
      epithelial cell types, syntaxin 2 may play an important role in this trafficking
      route in others.

PMID- 12198140
TI  - Altering the substrate specificity of cephalosporin acylase by directed evolution
      of the Beta -subunit.
AB  - Using directed evolution, we have selected an adipyl acylase enzyme that can be
      used for a one-step bioconversion of adipyl-7-aminodesacetoxycephalosporanic acid
      (adipyl-7-ADCA) to 7-ADCA, an important compound for the synthesis of
      semisynthetic cephalosporins. The starting point for the directed evolution was
      the glutaryl acylase from Pseudomonas SY-77. The gene fragment encoding the beta
      subunit was divided into five overlapping parts that were mutagenized separately
      using error-prone PCR. Mutants were selected in a leucine-deficient host using
      adipyl-leucine as the sole leucine source. In total, 24 out of 41 plate-selected
      mutants were found to have a significantly improved ratio of adipyl-7-ADCA versus
      glutaryl-7-ACA hydrolysis. Several mutations around the substrate-binding site
      were isolated, especially in two hot spot positions: residues Phe-375 and Asn
      266. Five mutants were further characterized by determination of their Michaelis
      Menten parameters. Strikingly, mutant SY-77(N266H) shows a nearly 10-fold
      improved catalytic efficiency (k(cat)/K(m)) on adipyl-7-ADCA, resulting from a
      50% increase in k(cat) and a 6-fold decrease in K(m), without decreasing the
      catalytic efficiency on glutaryl-7-ACA. In contrast, the improved adipyl/glutaryl
      activity ratio of mutant SY-77(F375L) mainly is a consequence of a decreased
      catalytic efficiency toward glutaryl-7-ACA. These results are discussed in the
      light of a structural model of SY-77 glutaryl acylase.

PMID- 12198141
TI  - The crystal structure of the quorum sensing protein TraR bound to its autoinducer
      and target DNA.
AB  - The quorum sensing system allows bacteria to sense their cell density and
      initiate an altered pattern of gene expression after a sufficient quorum of cells
      has accumulated. In Agrobacterium tumefaciens, quorum sensing controls conjugal
      transfer of the tumour- inducing plasmid, responsible for plant crown gall
      disease. The core components of this system are the transcriptional regulator
      TraR and its inducing ligand N-(3-oxo-octanoyl)-L-homoserine lactone. This
      complex binds DNA and activates gene expression. We have determined the crystal
      structure of TraR in complex with its autoinducer and target DNA (PDB code 1h0m).
      The protein is dimeric, with each monomer composed of an N-terminal domain, which
      binds the ligand in an enclosed cavity far from the dimerization region, and a C
      terminal domain, which binds DNA via a helix-turn-helix motif. The structure
      reveals an asymmetric homodimer, with one monomer longer than the other. The N
      terminal domain resembles GAF/PAS domains, normally fused to catalytic signalling
      domains. In TraR, the gene fusion is between a GAF/PAS domain and a DNA-binding
      domain, resulting in a specific transcriptional regulator involved in quorum
      sensing.

PMID- 12198142
TI  - Acid-induced movements in the glycoprotein shell of an alphavirus turn the spikes
      into membrane fusion mode.
AB  - In the icosahedral (T = 4) Semliki Forest virus, the envelope protomers, i.e. E1
      E2 heterodimers, make one-to-one interactions with capsid proteins below the
      viral lipid bilayer, transverse the membrane and form an external glycoprotein
      shell with projections. The shell is organized by protomer domains interacting as
      hexamers and pentamers around shell openings at icosahedral 2- and 5-fold axes,
      respectively, and the projections by other domains associating as trimers at 3-
      and quasi 3-fold axes. We show here, using cryo- electron microscopy, that low
      pH, as occurs in the endosomes during virus uptake, results in the relaxation of
      protomer interactions around the 2- and the 5-fold axes in the shell, and
      movement of protomers towards 3- and quasi 3-fold axes in a way that reciprocally
      relocates their putative E1 and E2 domains. This seemed to be facilitated by a
      trimerization of transmembrane segments at the same axes. The alterations
      observed help to explain several key features of the spike-mediated membrane
      fusion reaction, including shell dissolution, heterodimer dissociation, fusion
      peptide exposure and E1 homotrimerization.

PMID- 12198144
TI  - A dynamically localized histidine kinase controls the asymmetric distribution of
      polar pili proteins.
AB  - Each cell division in Caulobacter crescentus is asymmetric, yielding a swarmer
      cell with several polar pili and a non-piliated stalked cell. To identify factors
      contributing to the asymmetric biogenesis of polar pili, cytological studies of
      pilus assembly components were performed. We show here that the CpaC protein,
      which is thought to form the outer membrane pilus secretion channel, and its
      assembly factor, CpaE, are localized to the cell pole prior to the polymerization
      of the pilus filament. We demonstrate that the PleC histidine kinase, a two
      component signal transduction protein shown previously to localize to the
      piliated cell pole before and during pilus assembly, controls the accumulation of
      the pilin subunit, PilA. Using an inactive form of PleC (PleCH610A) that lacks
      the catalytic histidine residue, we provide evidence that PleC activity is
      responsible for the asymmetric distribution of CpaE and itself to only one of the
      two cell poles. Thus, a polar signal transduction protein controls its own
      asymmetric location as well as that of a factor assembling a polar organelle.

PMID- 12198143
TI  - A mitochondrial specific stress response in mammalian cells.
AB  - Cells respond to a wide variety of stresses through the transcriptional
      activation of genes that harbour stress elements within their promoters. While
      many of these elements are shared by genes encoding proteins representative of
      all subcellular compartments, cells can also respond to stresses that are
      specific to individual organelles, such as the endoplasmic reticulum un folded
      protein response. Here we report on the discovery and characterization of a
      mitochondrial stress response in mammalian cells. We find that the accumulation
      of unfolded protein within the mitochondrial matrix results in the
      transcriptional upregulation of nuclear genes encoding mitochondrial stress
      proteins such as chaperonin 60, chaperonin 10, mtDnaJ and ClpP, but not those
      encoding stress proteins of the endoplasmic reticulum. Analysis of the chaperonin
      60/10 bidirectional promoter identified a CHOP element as the mitochondrial
      stress response element. Dominant-negative mutant forms of CHOP and
      overexpression of CHOP revealed that this transcription factor, in association
      with C/EBPbeta, regulates expression of mitochondrial stress genes in response to
      the accumulation of unfolded proteins.

PMID- 12198145
TI  - Glycolysis modulates trypanosome glycoprotein expression as revealed by an RNAi
      library.
AB  - RNA interference (RNAi) is a powerful tool for identifying gene function in
      Trypanosoma brucei. We generated an RNAi library, the first of its kind in any
      organism, by ligation of genomic fragments into the vector pZJMbeta. After
      transfection at approximately 5-fold genome coverage, trypanosomes were induced
      to express double-stranded RNA and screened for reduced con canavalin A (conA)
      binding. Since this lectin binds the surface glycoprotein EP-procyclin, we
      predicted that cells would lose affinity to conA if RNAi silenced genes affecting
      EP-procyclin expression or modification. We found a cell line in which RNAi
      switches expression from glycosylated EP-procyclins to the unglycosylated GPEET
      procyclin. This switch results from silencing a hexokinase gene. The relationship
      between procyclin expression and glycolysis was supported by silencing other
      genes in the glycolytic pathway, and confirmed by observation of a similar
      upregulation of GPEET- procyclin when parental cells were grown in medium
      depleted of glucose. These data suggest that T.brucei 'senses' changes in glucose
      level and modulates procyclin expression accordingly.

PMID- 12198147
TI  - Initial steps of Shigella infection depend on the cholesterol/sphingolipid raft
      mediated CD44-IpaB interaction.
AB  - Shigellosis is an acute inflammatory bowel disease caused by the enteroinvasive
      bacterium SHIGELLA: Upon host cell-Shigella interaction, major host cell
      signalling responses are activated. Deciphering the initial molecular events is
      crucial to understanding the infectious process. We identified a molecular
      complex involving proteins of both the host, CD44 the hyaluronan receptor, and
      Shigella, the invasin IpaB, which partitions during infection within specialized
      membrane microdomains enriched in cholesterol and sphingolipids, called rafts. We
      also document accumulation of cholesterol and raft-associated proteins at
      Shigella entry foci. Moreover, we report that Shigella entry is impaired after
      cholesterol depletion using methyl-beta-cyclodextrin. Finally, we find that
      Shigella is less invasive in sphingosid-based lipid-deficient cell lines,
      demonstrating the involvement of sphingolipids. Our results show that rafts are
      implicated in Shigella binding and entry, suggesting that raft-associated
      molecular machineries are engaged in mediating the cell signalling response
      required for the invasion process.

PMID- 12198146
TI  - p11, an annexin II subunit, an auxiliary protein associated with the background
      K+ channel, TASK-1.
AB  - TASK-1 belongs to the 2P domain K+ channel family and is the prototype of
      background K+ channels that set the resting membrane potential and tune action
      potential duration. Its activity is highly regulated by hormones and
      neurotransmitters. Although numerous auxiliary proteins have been described to
      modify biophysical, pharmacological and expression properties of different
      voltage- and Ca2+-sensitive K+ channels, none of them is known to modulate 2P
      domain K+ channel activity. We show here that p11 interacts specifically with the
      TASK-1 K+ channel. p11 is a subunit of annexin II, a cytoplasmic protein thought
      to bind and organize specialized membrane cytoskeleton compartments. This
      association with p11 requires the integrity of the last three C-terminal amino
      acids, Ser-Ser-Val, in TASK-1. Using series of C-terminal TASK-1 deletion mutants
      and several TASK-1-GFP chimeras, we demonstrate that association with p11 is
      essential for trafficking of TASK-1 to the plasma membrane. p11 association with
      the TASK-1 channel masks an endoplasmic reticulum retention signal identified as
      Lys-Arg-Arg that precedes the Ser-Ser-Val sequence.

PMID- 12198148
TI  - Leishmania LPG3 encodes a GRP94 homolog required for phosphoglycan synthesis
      implicated in parasite virulence but not viability.
AB  - Leishmania promastigotes express an abundant cell surface glycoconjugate,
      lipophosphoglycan (LPG). LPG contains a polymer of the disaccharide-phosphate
      repeat unit Galbeta1,4Manalpha1-PO4, shared by other developmentally regulated
      molecules implicated in parasite virulence. Functional complementation of a
      Leishmania donovani LPG-defective mutant (OB1) accumulating a truncated LPG
      containing only the Manalpha1-PO4 residue of the first repeat unit identified
      LPG3, the Leishmania homolog of the mammalian endoplasmic reticulum (ER)
      chaperone GRP94. LPG3 resembles GRP94, as it localizes to the parasite ER, and
      lpg3(-) mutants show defects including down-regulation of surface GPI-anchored
      proteins and mild effects on other glycoconjugates. LPG3 binds cellular proteins
      and its Leishmania infantum GRP94 ortholog is highly immunogenic, suggesting a
      potential role in directing the immune response. However, null lpg3(-) mutants
      grow normally, are completely defective in the synthesis of phosphoglycans, and
      the LPG3 mRNA is regulated developmentally but not by stress or heat. Thus the
      role of LPG3/GRP94 in Leishmania metabolism differs significantly from other
      eukaryotes. Like the other glycoconjugate synthetic pathways in this parasite,
      its activity is focused on molecules implicated in virulence rather than
      viability.

PMID- 12198149
TI  - Dissociation of the dimeric SecA ATPase during protein translocation across the
      bacterial membrane.
AB  - The ATPase SecA mediates post-translational translocation of precursor proteins
      through the SecYEG channel of the bacterial inner membrane. We show that SecA, up
      to now considered to be a stable dimer, is actually in equilibrium with a small
      fraction of monomers. In the presence of membranes containing acidic
      phospholipids or in certain detergents, SecA completely dissociates into
      monomers. A synthetic signal peptide also affects dissociation into monomers. In
      addition, conversion into the monomeric state can be achieved by mutating a small
      number of residues in a dimeric and fully functional SecA fragment. This
      monomeric SecA fragment still maintains strong binding to SecYEG in the membrane
      as well as significant in vitro translocation activity. Together, the data
      suggest that the SecA dimer dissociates during protein translocation. Since SecA
      contains all characteristic motifs of a certain class of monomeric helicases, and
      since mutations in residues shared with the helicases abolish its translocation
      activity, SecA may function in a similar manner.

PMID- 12198151
TI  - Suppression of the STK15 oncogenic activity requires a transactivation
      independent p53 function.
AB  - Using a transactivation-defective p53 derivative as bait, STK15, a centrosome
      associated oncogenic serine/threonine kinase, was isolated as a p53 partner. The
      p53-STK15 interaction was confirmed further by co-immunoprecipitation and GST
      pull-down studies. In co-transfection experiments, p53 suppressed STK15-induced
      centrosome amplification and cellular transformation in a transactivation
      independent manner. The suppression of STK15 oncogenic activity by p53 might be
      explained in part by the finding that p53 inhibited STK15 kinase activity via
      direct interaction with the latter's Aurora box. Taken together, these findings
      revealed a novel mechanism for the tumor suppressor function of p53.

PMID- 12198150
TI  - Vesicle transmembrane potential is required for translocation to the cytosol of
      externally added FGF-1.
AB  - Externally added fibroblast growth factor-1 (FGF-1) is capable of crossing
      cellular membranes to reach the cytosol and the nucleus in a number of cell
      types. We have monitored the translocation of the growth factor by two methods:
      phosphorylation of FGF-1, and prenylation of an FGF-1 mutant that contains a C
      terminal prenylation signal. Inhibition of endosomal acidification by ammonium
      chloride or monensin did not block the translocation of FGF-1, whereas
      bafilomycin A1, a specific inhibitor of vacuolar proton pumps, blocked
      translocation completely. A combination of ionophores expected to dissipate the
      vesicular membrane potential (valinomycin plus monensin) also fully inhibited the
      translocation. The inhibition of translocation by bafilomycin A1 was overcome in
      the presence of monensin or nigericin, while ouabain blocked translocation under
      these conditions. The data indicate that translocation of FGF-1 to cytosol occurs
      from the lumen of intracellular vesicles possessing vacuolar proton pumps, and
      that a vesicular membrane potential is required. Apparently, activation of
      vesicular Na+/K+-ATPase by monensin or nigericin generates a membrane potential
      that can support translocation when the proton pump is blocked.

PMID- 12198153
TI  - Interaction between domains of a plant NBS-LRR protein in disease resistance
      related cell death.
AB  - Many plant disease resistance (R) genes encode proteins predicted to have an N
      terminal coiled-coil (CC) domain, a central nucleotide-binding site (NBS) domain
      and a C-terminal leucine-rich repeat (LRR) domain. These CC-NBS-LRR proteins
      recognize specific pathogen-derived products and initiate a resistance response
      that often includes a type of cell death known as the hypersensitive response
      (HR). Co-expression of the potato CC-NBS-LRR protein Rx and its elicitor, the PVX
      coat protein (CP), results in a rapid HR. Surprisingly, co-expression of the LRR
      and CC-NBS as separate domains also resulted in a CP-dependent HR. Likewise, the
      CC domain complemented a version of Rx lacking this domain (NBS- LRR).
      Correspondingly, the LRR domain interacted physically in planta with the CC-NBS,
      as did CC with NBS-LRR. Both interactions were disrupted in the presence of CP.
      However, the interaction between CC and NBS-LRR was dependent on a wild-type P
      loop motif, whereas the interaction between CC-NBS and LRR was not. We propose
      that activation of Rx entails sequential disruption of at least two
      intramolecular interactions.

PMID- 12198152
TI  - Timing of APC/C substrate degradation is determined by fzy/fzr specificity of
      destruction boxes.
AB  - The anaphase promoting complex/cyclosome (APC/C), activated by fzy and fzr,
      degrades cell cycle proteins that carry RXXL or KEN destruction boxes (d-boxes).
      APC/C substrates regulate sequential events and must be degraded in the correct
      order during mitosis and G(1). We studied how d-boxes determine
      APC/C(fzy)/APC/C(fzr) specificity and degradation timing. Cyclin B1 has an RXXL
      box and is degraded by both APC/C(fzy) and APC/C(fzr); fzy has a KEN box and is
      degraded by APC/C(fzr) only. We characterized the degradation of substrates with
      swapped d-boxes. Cyclin B1 with KEN was degraded by APC/C(fzr) only. Fzy with
      RXXL could be degraded by APC/C(fzy) and APC/C(fzr). Interestingly, APC/C(fzy)-
      but not APC/C(fzr)-specific degradation is highly dependent on the location of
      RXXL. We studied degradation of tagged substrates in real time and observed that
      APC/C(fzr) is activated in early G(1). These observations demonstrate how d-box
      specificities of APC/C(fzy) and APC/C(fzr), and the successive activation of
      APC/C by fzy and fzr, establish the temporal degradation pattern. Our
      observations can explain further why some endogenous RXXL substrates are degraded
      by APC/C(fzy), while others are restricted to APC/C(fzr).

PMID- 12198154
TI  - Caspase-10 is recruited to and activated at the native TRAIL and CD95 death
      inducing signalling complexes in a FADD-dependent manner but can not functionally
      substitute caspase-8.
AB  - The involvement of the death adaptor protein FADD and the apoptosis-initiating
      caspase-8 in CD95 and TRAIL death signalling has recently been demonstrated by
      the analysis of the native death-inducing signalling complex (DISC) that forms
      upon ligand-induced receptor cross-linking. However, the role of caspase-10, the
      other death-effector-domain-containing caspase besides caspase-8, in death
      receptor signalling has been controversial. Here we show that caspase-10 is
      recruited not only to the native TRAIL DISC but also to the native CD95 DISC, and
      that FADD is necessary for its recruitment to and activation at these two protein
      complexes. With respect to the function of caspase-10, we show that it is not
      required for apoptosis induction. In addition, caspase-10 can not substitute for
      caspase-8, as the defect in apoptosis induction observed in caspase-8-deficient
      cells could not be rescued by overexpression of caspase-10. Finally, we
      demonstrate that caspase-10 is cleaved during CD95-induced apoptosis of activated
      T cells. These results show that caspase-10 activation occurs in primary cells,
      but that its function differs from that of caspase-8.

PMID- 12198155
TI  - An inositol 1,4,5-trisphosphate receptor-dependent cation entry pathway in DT40 B
      lymphocytes.
AB  - We examined the roles of inositol 1,4,5-trisphosphate (IP3) receptors (IP3R) in
      calcium signaling using DT40 B lymphocytes, and a variant lacking the three IP3R
      isoforms (IP3R-KO). In wild-type cells, B cell receptor (BCR) stimulation
      activates a cation entry route that exhibits significantly greater permeability
      to Ba2+ than does capacitative calcium entry. This cation entry is absent in IP3R
      KO cells. Expression of the type-3 IP3R (IP3R-3) in the IP3R-KO cells rescued not
      only agonist-dependent release of intracellular Ca2+, but also Ba2+ influx
      following receptor stimulation. Similar results were obtained with an IP3R-3
      mutant carrying a conservative point mutation in the selectivity filter region of
      the channel (D2477E); however, an IP3R-3 mutant in which this same aspartate was
      replaced by alanine (D2477A) failed to restore either BCR-induced Ca2+ release or
      receptor-dependent Ba2+ entry. These results suggest that in DT40 B lymphocytes,
      BCR stimulation activates a novel cation entry across the plasma membrane that
      depends upon, or is mediated by, fully functional IP3R.

PMID- 12198156
TI  - Defects in cytokinesis, actin reorganization and the contractile vacuole in cells
      deficient in RhoGDI.
AB  - Rho GDP-dissociation inhibitors (RhoGDIs) modulate the cycling of Rho GTPases
      between active GTP-bound and inactive GDP-bound states. We identified two RhoGDI
      homologues in DICTYOSTELIUM: GDI1 shares 51-58% similarity to RhoGDIs from
      diverse species. GDI2 is more divergent (40-44% similarity) and lacks the N
      terminal regulatory arm characteristic for RhoGDI proteins. Both are cytosolic
      proteins and do not relocalize upon reorganization of the actin cytoskeleton.
      Using a two-hybrid approach, we identified Rac1a/1b/1c, RacB, RacC and RacE as
      interacting partners for GDI1. Cells lacking GDI1 are multinucleate, grow slowly
      and display a moderate pinocytosis defect, but rates of phagocytosis are
      unaffected. Mutant cells present prominent actin-rich protrusions, and large
      vacuoles that are continuous with the contractile vacuole system. The actin
      polymerization response upon stimulation with cAMP was reduced, but the motile
      behavior toward the chemoattractant was unaffected. Our results indicate that
      GDI1 plays a central role in the regulation of signal transduction cascades
      mediated by Rho GTPases.

PMID- 12198157
TI  - A cell-cell signaling peptide activates the PlcR virulence regulon in bacteria of
      the Bacillus cereus group.
AB  - PlcR is a pleiotropic regulator that activates the expression of genes encoding
      various virulence factors, such as phospholipases C, proteases and hemolysins, in
      Bacillus thuringiensis and Bacillus cereus. Here we show that the activation
      mechanism is under the control of a small peptide: PapR. The papR gene belongs to
      the PlcR regulon and is located 70 bp downstream from plcR. It encodes a 48-amino
      acid peptide. Disruption of the papR gene abolished expression of the PlcR
      regulon, resulting in a large decrease in hemolysis and virulence in insect
      larvae. We demonstrated that the PapR polypeptide was secreted, then reimported
      via the oligopeptide permease Opp. Once inside the cell, a processed form of
      PapR, presumably a pentapeptide, activated the PlcR regulon by allowing PlcR to
      bind to its DNA target. This activating mechanism was found to be strain
      specific, with this specificity determined by the first residue of the penta
      peptide.

PMID- 12198158
TI  - A novel cGMP signalling pathway mediating myosin phosphorylation and chemotaxis
      in Dictyostelium.
AB  - Chemotactic stimulation of Dictyostelium cells results in a transient increase in
      cGMP levels, and transient phosphorylation of myosin II heavy and regulatory
      light chains. In Dictyostelium, two guanylyl cyclases and four candidate cGMP
      binding proteins (GbpA- GbpD) are implicated in cGMP signalling. GbpA and GbpB
      are homologous proteins with a Zn2+-hydrolase domain. A double gbpA/gbpB gene
      disruption leads to a reduction of cGMP-phosphodiesterase activity and a 10-fold
      increase of basal and stimulated cGMP levels. Chemotaxis in gbpA(-)B(-) cells is
      associated with increased myosin II phosphorylation compared with wild-type
      cells; formation of lateral pseudopodia is suppressed resulting in enhanced
      chemotaxis. GbpC is homologous to GbpD, and contains Ras, MAPKKK and Ras-GEF
      domains. Inactivation of the gbp genes indicates that only GbpC harbours high
      affinity cGMP-binding activity. Myosin phosphorylation, assembly of myosin in the
      cytoskeleton as well as chemotaxis are severely impaired in mutants lacking GbpC
      and GbpD, or mutants lacking both guanylyl cyclases. Thus, a novel cGMP
      signalling cascade is critical for chemotaxis in Dictyostelium, and plays a major
      role in myosin II regulation during this process.

PMID- 12198159
TI  - Tyrosine 221 in Crk regulates adhesion-dependent membrane localization of Crk and
      Rac and activation of Rac signaling.
AB  - The adaptor protein CrkII plays a central role in signal transduction cascades
      downstream of a number of different stimuli. We and others have previously shown
      that CrkII mediates attachment-induced JNK activation, membrane ruffling and cell
      motility in a Rac-dependent manner. We report here that cell attachment leads to
      tyrosine phosphorylation of CrkII on Y221, and that CrkII-Y221F mutant
      demonstrates enhanced association with the Crk-binding partners C3G and paxillin.
      Despite this enhanced signaling complex formation, CrkII-Y221F fails to induce
      JNK and PAK activation, membrane ruffling and cell migration, suggesting that it
      is defective in activating Rac signaling. Wild-type CrkII has no effect on
      adhesion-induced GTP loading of Rac, but its expression results in enhanced
      membrane localization of Rac, which is known to be required for Rac signaling. In
      contrast, CrkII-Y221F is deficient in enhancing membrane localization of Rac.
      Mutations in Rac and CrkII-Y221F that force membrane targeting of these molecules
      restore Rac signaling in adherent cells. Together, these results indicate that
      the Y221 site in CrkII regulates Rac membrane translocation upon cell adhesion,
      which is necessary for activation of downstream Rac signaling pathways.

PMID- 12198160
TI  - Ca2+-dependent block of CREB-CBP transcription by repressor DREAM.
AB  - The calcium-binding protein DREAM binds specifically to DRE sites in the DNA and
      represses transcription of target genes. Derepression at DRE sites following PKA
      activation depends on a specific interaction between alphaCREM and DREAM. Two
      leucine-charged residue-rich domains (LCD) located in the kinase-inducible domain
      (KID) and in the leucine zipper of alphaCREM and two LCDs in DREAM participate in
      a two-site interaction that results in the loss of DREAM binding to DRE sites and
      derepression. Since the LCD motif located within the KID in CREM is also present
      in CREB, and maps in a region critical for the recruitment of CBP, we
      investigated whether DREAM may affect CRE-dependent transcription. Here we show
      that in the absence of Ca2+ DREAM binds to the LCD in the KID of CREB. As a
      result, DREAM impairs recruitment of CBP by phospho CREB and blocks CBP-mediated
      transactivation at CRE sites in a Ca2+-dependent manner. Thus, Ca2+-dependent
      interactions between DREAM and CREB represent a novel point of cross-talk between
      cAMP and Ca2+ signalling pathways in the nucleus.

PMID- 12198161
TI  - Lymphatic endothelial reprogramming of vascular endothelial cells by the Prox-1
      homeobox transcription factor.
AB  - Lymphatic vessels are essential for fluid homeostasis, immune surveillance and
      fat adsorption, and also serve as a major route for tumor metastasis in many
      types of cancer. We found that isolated human primary lymphatic and blood
      vascular endothelial cells (LECs and BECs, respectively) show interesting
      differences in gene expression relevant for their distinct functions in vivo.
      Although these phenotypes are stable in vitro and in vivo, overexpression of the
      homeobox transcription factor Prox-1 in the BECs was capable of inducing LEC
      specific gene transcription in the BECs, and, surprisingly, Prox-1 suppressed the
      expression of approximately 40% of the BEC-specific genes. Prox-1 did not have
      global effects on the expression of LEC-specific genes in other cell types,
      except that it up-regulated cyclin E1 and E2 mRNAs and activated the cyclin e
      promoter in various cell types. These data suggest that Prox-1 acts as a cell
      proliferation inducer and a fate determination factor for the LECs. Furthermore,
      the data provide insights into the phenotypic diversity of endothelial cells and
      into the possibility of transcriptional reprogramming of differentiated
      endothelial cells.

PMID- 12198162
TI  - Structure and function of the BAH-containing domain of Orc1p in epigenetic
      silencing.
AB  - The N-terminal domain of the largest subunit of the Saccharomyces cerevisiae
      origin recognition complex (Orc1p) functions in transcriptional silencing and
      contains a bromo-adjacent homology (BAH) domain found in some chromatin
      associated proteins including Sir3p. The 2.2 A crystal structure of the N
      terminal domain of Orc1p revealed a BAH core and a non-conserved helical sub
      domain. Mutational analyses demonstrated that the helical sub-domain was
      necessary and sufficient to bind Sir1p, and critical for targeting Sir1p
      primarily to the cis-acting E silencers at the HMR and HML silent chromatin
      domains. In the absence of the BAH domain, approximately 14-20% of cells in a
      population were silenced at the HML locus. Moreover, the distributions of the
      Sir2p, Sir3p and Sir4p proteins, while normal, were at levels lower than found in
      wild-type cells. Thus, in the absence of the Orc1p BAH domain, HML resembled
      silencing of genes adjacent to telomeres. These data are consistent with the view
      that the Orc1p-Sir1p interaction at the E silencers ensures stable inheritance of
      pre-established Sir2p, Sir3p and Sir4p complexes at the silent mating type loci.

PMID- 12198163
TI  - A cell type-specific allele of the POU gene Oct-6 reveals Schwann cell autonomous
      function in nerve development and regeneration.
AB  - While an important role for the POU domain transcription factor Oct-6 in the
      developing peripheral nerve has been well established, studies into its exact
      role in nerve development and regeneration have been hampered by the high
      mortality rate of newborn Oct-6 mutant animals. In this study we have generated a
      Schwann cell-specific Oct-6 allele through deletion of the Schwann cell-specific
      enhancer element (SCE) in the Oct-6 locus. Analysis of mice homozygous for this
      allele (deltaSCE allele) reveals that rate-limiting levels of Oct-6 in Schwann
      cells are dependent on the SCE and that this element does not contribute to Oct-6
      regulation in other cell types. We demonstrate a Schwann cell autonomous function
      for Oct-6 during nerve development as well as in regenerating nerve.
      Additionally, we show that Krox-20, an important regulatory target of Oct-6 in
      Schwann cells, is activated, with delayed kinetics, through an Oct-6-independent
      mechanism in these mice.

PMID- 12198164
TI  - TIS7 interacts with the mammalian SIN3 histone deacetylase complex in epithelial
      cells.
AB  - The mammalian SIN3 complex consists of histone deacetylases (HDAC1, HDAC2),
      several known proteins (SAP30, N-CoR) and as yet unidentified proteins. Here we
      show that the mouse tetradecanoyl phorbol acetate induced sequence 7 (TIS7)
      protein is a novel transcriptional co-repressor that can associate with the SIN3
      complex. We have identified tis7 as a gene that is up-regulated upon loss of
      polarity in a mouse mammary gland epithelial cell line expressing an estrogen
      inducible c-JunER fusion protein. In unpolarized cells, TIS7 protein levels
      increase and TIS7 translocates into the nucleus. Overexpression of tis7 causes
      loss of polarity and represses a set of genes, as revealed by cDNA microarray
      analysis. We have shown that TIS7 protein interacts with several proteins of the
      SIN3 complex (mSin3B, HDAC1, N-CoR and SAP30) by yeast two-hybrid screening and
      co-immunoprecipitations. TIS7 co-immunoprecipitated HDAC complex is enzymatically
      active and represses a GAL4-dependent reporter transcription. The transcriptional
      repression of endogenous genes by tis7 overexpression is HDAC dependent. Thus, we
      propose TIS7 as a transcriptional co-repressor affecting the expression of
      specific genes in a HDAC activity-dependent manner during cell fate decisions,
      e.g. scattering.

PMID- 12198165
TI  - The chromatin remodeling complex NoRC targets HDAC1 to the ribosomal gene
      promoter and represses RNA polymerase I transcription.
AB  - Mammalian chromatin remodeling complexes are involved in both activation and
      repression of transcription. Here, we show that NoRC, a SNF2h- containing
      nucleolar chromatin remodeling complex, represses ribosomal gene transcription.
      NoRC-mediated rDNA silencing was alleviated by trichostatin A, indicating that
      histone deacetylation is causally involved in silencing. Chromatin
      immunoprecipitation experiments demonstrate that overexpression of TIP5, the
      large subunit of NoRC, mediates deacetylation of nucleosomes in the vicinity of
      the rDNA promoter. Protein-protein interaction assays reveal association of TIP5
      with the histone deacetylase HDAC1 in vivo and in vitro. Deletion of the C
      terminal PHD finger and bromodomain abolishes the interaction of TIP5 and HDAC1,
      and abrogates transcriptional repression. The results suggest that NoRC silences
      the rDNA locus by targeting the SIN3 corepressor complex to the rDNA promoter,
      thereby establishing a repressed chromatin structure.

PMID- 12198166
TI  - Crystal structures of transcription factor NusG in light of its nucleic acid- and
      protein-binding activities.
AB  - Microbial transcription modulator NusG interacts with RNA polymerase and
      termination factor rho, displaying striking functional homology to eukaryotic
      Spt5. The protein is also a translational regulator. We have determined crystal
      structures of Aquifex aeolicus NusG showing a modular design: an N-terminal RNP
      like domain, a C-terminal element with a KOW sequence motif and a species
      specific immunoglobulin-like fold. The structures reveal bona fide nucleic acid
      binding sites, and nucleic acid binding activities can be detected for NusG from
      three organisms and for the KOW element alone. A conserved KOW domain is defined
      as a new class of nucleic acid binding folds. This module is a close structural
      homolog of tudor protein-protein interaction motifs. Putative protein binding
      sites for the RNP and KOW domains can be deduced, which differ from the areas
      implicated in nucleic acid interactions. The results strongly argue that both
      protein and nucleic acid contacts are important for NusG's functions and that the
      factor can act as an adaptor mediating indirect protein-nucleic acid
      associations.

PMID- 12198167
TI  - Structure of Alba: an archaeal chromatin protein modulated by acetylation.
AB  - Eukaryotic DNA is packaged into nucleosomes that regulate the accessibility of
      the genome to replication, transcription and repair factors. Chromatin
      accessibility is controlled by histone modifications including acetylation and
      methylation. Archaea possess eukary otic-like machineries for DNA replication,
      transcription and information processing. The conserved archaeal DNA binding
      protein Alba (formerly Sso10b) interacts with the silencing protein Sir2, which
      regulates Alba's DNA binding affinity by deacetylation of a lysine residue. We
      present the crystal structure of Alba from Sulfolobus solfataricus at 2.6 A
      resolution (PDB code 1h0x). The fold is reminiscent of the N-terminal DNA binding
      domain of DNase I and the C-terminal domain of initiation factor IF3. The Alba
      dimer has two extended beta-hairpins flanking a central body containing the
      acetylated lysine, Lys16, suggesting three main points of contact with the DNA.
      Fluorescence, calorimetry and electrophoresis data suggest a final binding
      stoichiometry of approximately 5 bp DNA per Alba dimer. We present a model for
      the Alba-DNA interaction consistent with the available structural, biophysical
      and electron microscopy data.

PMID- 12198168
TI  - MicroRNA maturation: stepwise processing and subcellular localization.
AB  - MicroRNAs (miRNAs) constitute a novel, phylogenetically extensive family of small
      RNAs ( approximately 22 nucleotides) with potential roles in gene regulation.
      Apart from the finding that miRNAs are produced by Dicer from the precursors of
      approximately 70 nucleotides (pre-miRNAs), little is known about miRNA
      biogenesis. Some miRNA genes have been found in close conjunction, suggesting
      that they are expressed as single transcriptional units. Here, we present in vivo
      and in vitro evidence that these clustered miRNAs are expressed polycistronically
      and are processed through at least two sequential steps: (i) generation of the
      approximately 70 nucleotide pre-miRNAs from the longer transcripts (termed pri
      miRNAs); and (ii) processing of pre-miRNAs into mature miRNAs. Subcellular
      localization studies showed that the first and second steps are compartmentalized
      into the nucleus and cytoplasm, respectively, and that the pre-miRNA serves as
      the substrate for nuclear export. Our study suggests that the regulation of miRNA
      expression may occur at multiple levels, including the two processing steps and
      the nuclear export step. These data will provide a framework for further studies
      on miRNA biogenesis.

PMID- 12198170
TI  - Discrimination between mono- and trimethylated cap structures by two isoforms of
      Caenorhabditis elegans eIF4E.
AB  - Primitive eukaryotes like Caenorhabditis elegans produce mRNAs capped with either
      m(7)GTP or m(3)(2,2,7)GTP. Caenorhabditis elegans also expresses five isoforms of
      the cap-binding protein eIF4E. Some isoforms (e.g. IFE-3) bind to m(7)GTP
      Sepharose exclusively, whereas others (e.g. IFE-5) bind to both m(7)GTP- and
      m(3)(2,2,7)GTP-Sepharose. To examine specificity differences, we devised
      molecular models of the tertiary structures of IFE-3 and IFE-5, based on the
      known structure of mouse eIF4E-1. We then substituted amino acid sequences of IFE
      5 with homologous sequences from IFE-3. As few as two changes (N64Y/V65L)
      converted the cap specificity of IFE-5 to essentially that of IFE-3. Molecular
      dynamics simulations suggested that the width and depth of the cap-binding cavity
      were larger in IFE-5 than in IFE-3 or the N64Y/V65L variant, supporting a model
      in which IFE-3 discriminates against m(3)(2,2,7)GTP by steric hindrance.
      Furthermore, the affinity of IFE-5 (but not IFE-3) for m(3)(2,2,7)GTP was
      reversibly increased when thiol reagents were removed. This was correlated with
      the formation of a disulfide bond between Cys-122 and Cys-126. Thus, translation
      of m(3)(2,2,7)GTP-capped mRNAs may be regulated by intracellular redox state.

PMID- 12198169
TI  - Two classes of short interfering RNA in RNA silencing.
AB  - RNA silencing is a eukaryotic genome defence system that involves processing of
      double-stranded RNA (dsRNA) into 21-26 nt, short interfering RNA (siRNA). The
      siRNA mediates suppression of genes corresponding to the dsRNA through targeted
      RNA degradation. In some plant systems there are additional silencing processes,
      involving systemic spread of silencing and RNA-directed
      methylation/transcriptional suppression of homologous genomic DNA. We show here
      that siRNAs produced in plants from a green fluorescent protein (GFP) transgene
      are in short (21-22 nt) and long (24-26 nt) size classes, whereas those from
      endogenous retroelements are only in the long class. Viral suppressors of RNA
      silencing and mutations in Arabidopsis indicate that these classes of siRNA have
      different roles. The long siRNA is dispensable for sequence-specific mRNA
      degradation, but correlates with systemic silencing and methylation of homologous
      DNA. Conversely, the short siRNA class correlates with mRNA degradation but not
      with systemic signalling or methylation. These findings reveal an unexpected
      level of complexity in the RNA silencing pathway in plants that may also apply in
      animals.

PMID- 12198171
TI  - 4-thio-U cross-linking identifies the active site of the VS ribozyme.
AB  - To identify nucleotides in or near the active site, we have used a circularly
      permuted version of the VS ribozyme capable of cleavage and ligation to
      incorporate a single photoactive nucleotide analog, 4-thio- uridine, immediately
      downstream of the scissile bond. Exposure to UV light produced two cross-linked
      RNAs, in which the 4-thio-uridine was cross-linked to A756 in the 730 loop of
      helix VI. The cross-links formed only under conditions that support catalytic
      activity, suggesting that they reflect functionally relevant conformations of the
      RNA. One of the cross-linked RNAs contains a lariat, indicative of intramolecular
      cross-linking in the ligated RNA; the other is a branched molecule in which the
      scissile phosphodiester bond is cleaved, but occupies the same site in the
      ribozyme-substrate complex. These are the two forms of the RNA expected to be the
      ground state structures on either side of the transition state. This localization
      of the active site is consistent with previous mutational, biochemical and
      biophysical data, and provides direct evidence that the cleavage site in helix I
      interacts with the 730 loop in helix VI.

PMID- 12198172
TI  - The scavenger mRNA decapping enzyme DcpS is a member of the HIT family of
      pyrophosphatases.
AB  - We recently demonstrated that the major decapping activity in mammalian cells
      involves DcpS, a scavenger pyrophosphatase that hydrolyzes the residual cap
      structure following 3' to 5' decay of an mRNA. The association of DcpS with 3' to
      5' exonuclease exosome components suggests that these two activities are linked
      and there is a coupled exonucleolytic decay-dependent decapping pathway. We
      purified DcpS from mammalian cells and identified the cDNA encoding a novel 40
      kDa protein possessing DcpS activity. Consistent with purified DcpS, the
      recombinant protein specifically hydrolyzed methylated cap analog but did not
      hydrolyze unmethylated cap analog nor did it function on intact capped RNA.
      Sequence alignments of DcpS from different organisms revealed the presence of a
      conserved hexapeptide, containing a histidine triad (HIT) sequence with three
      histidines separated by hydrophobic residues. Mutagenesis analysis revealed that
      the central histidine within the DcpS HIT motif is critical for decapping
      activity and defines the HIT motif as a new mRNA decapping domain, making DcpS
      the first member of the HIT family of proteins with a defined biological
      function.

PMID- 12198173
TI  - Functional cloning of BRF1, a regulator of ARE-dependent mRNA turnover.
AB  - To identify regulators of AU-rich element (ARE)-dependent mRNA turnover we have
      followed a genetic approach using a mutagenized cell line (slowC) that fails to
      degrade cytokine mRNA. Accordingly, a GFP reporter construct whose mRNA is under
      control of the ARE from interleukin-3 gives an increased fluorescence signal in
      slowC. Here we describe rescue of slowC by a retroviral cDNA library. Flow
      cytometry allowed us to isolate revertants with reconstituted rapid mRNA decay.
      The cDNA was identified as butyrate response factor-1 (BRF1), encoding a zinc
      finger protein homologous to tristetraprolin. Mutant slowC carries frame-shift
      mutations in both BRF1 alleles, whereas slowB with intermediate decay kinetics is
      heterozygous. By use of small interfering (si)RNA, independent evidence for an
      active role of BRF1 in mRNA degradation was obtained. In transiently transfected
      NIH 3T3 cells, BRF1 accelerated mRNA decay and antagonized the stabilizing effect
      of PI3-kinase, while mutation of the zinc fingers abolished both function and ARE
      binding activity. This approach, which identified BRF1 as an essential regulator
      of ARE-dependent mRNA decay, should also be applicable to other cis-elements of
      mRNA turnover.

PMID- 12198175
TI  - Recombination-dependent mtDNA partitioning: in vivo role of Mhr1p to promote
      pairing of homologous DNA.
AB  - Yeast mhr1-1 was isolated as a defective mutation in mitochondrial DNA (mtDNA)
      recombination. About half of mhr1-1 cells lose mtDNA during growth at a higher
      temperature. Here, we show that mhr1-1 exhibits a defect in the partitioning of
      nascent mtDNA into buds and is a base-substitution mutation in MHR1 encoding a
      mitochondrial matrix protein. We found that the Mhr1 protein (Mhr1p) has activity
      to pair single-stranded DNA and homologous double-stranded DNA to form
      heteroduplex joints in vitro, and that mhr1-1 causes the loss of this activity,
      indicating its role in homologous mtDNA recombination. While the majority of the
      mtDNA in the mother cells consists of head-to-tail concatemers, more than half of
      the mtDNA in the buds exists as genome-sized monomers. The mhr1-1 deltacce1
      double mutant cells do not maintain any mtDNA, indicating the strict dependence
      of mtDNA maintenance on recombination functions. These results suggest a
      mechanism for mtDNA inheritance similar to that operating in the replication and
      packaging of phage DNA.

PMID- 12198174
TI  - Enhanced repair of cyclobutane pyrimidine dimers and improved UV resistance in
      photolyase transgenic mice.
AB  - During evolution, placental mammals appear to have lost cyclobutane pyrimidine
      dimer (CPD) photolyase, an enzyme that efficiently removes UV-induced CPDs from
      DNA in a light-dependent manner. As a consequence, they have to rely solely on
      the more complex, and for this lesion less efficient, nucleotide excision repair
      pathway. To assess the contribution of poor repair of CPDs to various biological
      effects of UV, we generated mice expressing a marsupial CPD photolyase transgene.
      Expression from the ubiquitous beta-actin promoter allowed rapid repair of CPDs
      in epidermis and dermis. UV-exposed cultured dermal fibroblasts from these mice
      displayed superior survival when treated with photoreactivating light. Moreover,
      photoreactivation of CPDs in intact skin dramatically reduced acute UV effects
      like erythema (sunburn), hyperplasia and apoptosis. Mice expressing the
      photolyase from keratin 14 promoter photo reactivate CPDs in basal and early
      differentiating keratinocytes only. Strikingly, in these animals, the anti
      apoptotic effect appears to extend to other skin compartments, suggesting the
      presence of intercellular apoptotic signals. Thus, providing mice with CPD
      photolyase significantly improves repair and uncovers the biological effects of
      CPD lesions.

PMID- 12198177
TI  - Meeting report: the next interleukin?
AB  - A report of the meeting "Third International Conference on Osteopontin and
      Related Proteins", San Antonio, TX, USA, 10 to 12 May 2002. At a recent meeting,
      the structure and biology of the cytokine osteopontin were discussed. The
      molecule is essential for cellular immune responses and for the remodeling of
      cardiovasculature and bone. Osteopontin is extensively modified by
      posttranslational modifications, the consequences of which are only beginning to
      be understood. In disease, the expression of osteopontin by cancers may enhance
      their malignant phenotype, possibly reflecting the ability of the cytokine to
      induce cell migration after ligation of integrins and CD44 variants. A gene
      family with osteopontin as a member has been characterized.

PMID- 12198178
TI  - Confirming specificity of RNAi in mammalian cells.
AB  - RNA interference (RNAi) is a process of sequence-specific gene silencing. Recent
      advances in the understanding of RNAi have provided practical tools to silence
      gene expression in mammalian cells, opening new possibilities for studying the
      functions of genes and proteins. It is important to ensure that an observed
      effect of RNAi is due to silencing of the intended target. Indeed, it is possible
      that an siRNA may silence more than one messenger RNA that is homologous in the
      region complementary to the siRNA. Considering that we know little about how RNAi
      works in mammalian cells, other artifacts may be yet to be recognized. Thus, we
      suggest approaches to rescue the effect of RNAi by ectopically expressing the
      protein of interest. These approaches involve introducing silent mutations into
      the complementary DNA of the protein and targeting RNAi to the untranslated
      regions of the gene.

PMID- 12198176
TI  - Interference of papillomavirus E6 protein with single-strand break repair by
      interaction with XRCC1.
AB  - XRCC1 protein is required for the repair of DNA single-strand breaks and genetic
      stability, and is essential for viability in mammals. XRCC1 functions as a
      scaffold protein by interacting and modulating polypeptide components of the
      single-strand break repair machinery, including AP endonuclease-1, DNA ligase
      IIIalpha, poly (ADP-ribose) polymerase, DNA polymerase beta and human
      polynucleotide kinase. We show here that the E6 protein of human papillomavirus
      type 1, 8 and 16 directly binds XRCC1. When tested in CHO derived XRCC1 'knock
      out' EM9 cells, co-expression of human papillomavirus 16 E6 with human XRCC1
      reduced the ability of the latter protein to correct the methyl methane sulfate
      sensitivity of XRCC1 mutant CHO cell line EM9. These data identify a novel link
      between small DNA tumour viruses and DNA repair pathways, and suggest a novel
      explanation for the development of genomic instability in tissue cells
      persistently infected with papillomaviruses.

PMID- 12198179
TI  - Mutagenesis and repair by low doses of alpha radiation in mammalian cells.
AB  - Low doses of alpha radiation in basements have been causally implicated in lung
      cancer. Previous studies have concentrated on high dose effects, for which no
      significant repair was found. In the present study, the methodology for measuring
      mutation by quantitating mitotic breaks and gaps was found to be applicable to G2
      phase Chinese hamster ovary cells irradiated with 10-50 cGy of alpha radiation.
      The mutation yield in such cells closely resembles that of gamma irradiation.
      Caffeine, which inhibits repair, produces the same straight line increase of
      alpha and gamma mutation yields plotted against the dose. In the absence of
      caffeine, the repair of alpha radiation lesions is almost twice as great as for
      gamma radiation. Mitotic index changes substantiate these interpretations. It is
      proposed that the higher ion density associated with alpha radiation may result
      in fewer lesions being missed by the repair processes. The quantitation of
      chromosomal lesions for G2 cells exposed to low doses of alpha radiation, gamma
      radiation, or chemical mutagens in the presence and absence of caffeine is a
      rapid and reproducible methodology. Protection from mutational disease in a
      fashion similar to the use of sanitation for infectious disease appears
      practical.

PMID- 12198180
TI  - Friction traced to the single atom.
AB  - Friction is caused by dissipative lateral forces that act between macroscopic
      objects. An improved understanding of friction is therefore expected from
      measurements of dissipative lateral forces acting between individual atoms. Here
      we establish atomic resolution of both conservative and dissipative forces by
      lateral force microscopy, presenting the resolution of atomic defects. The
      interaction between a single-tip atom that is oscillated parallel to an Si(111)
      (7 x 7) surface is measured. A dissipation energy of up to 4 eV per oscillation
      cycle is found. The dissipation is explained by a "plucking action of one atom on
      to the other" as described by G. A. Tomlinson in 1929 [Tomlinson, G. A. (1929)
      Phil. Mag. 7, 905-939].

PMID- 12198181
TI  - Pyrimethamine and WR99210 exert opposing selection on dihydrofolate reductase
      from Plasmodium vivax.
AB  - Plasmodium vivax is a major public health problem in Asia and South and Central
      America where it is most prevalent. Until very recently, the parasite has been
      effectively treated with chloroquine, but resistance to this drug has now been
      reported in several areas. Affordable alternative treatments for vivax malaria
      are urgently needed. Pyrimethamine-sulfadoxine is an inhibitor of dihydrofolate
      reductase (DHFR) that has been widely used to treat chloroquine-resistant
      Plasmodium falciparum malaria. DHFR inhibitors have not been considered for
      treatment of vivax malaria, because initial trials showed poor efficacy against
      P. vivax. P. vivax cannot be grown in culture; the reason for its resistance to
      DHFR inhibitors is unknown. We show that, like P. falciparum, point mutations in
      the dhfr gene can cause resistance to pyrimethamine in P. vivax. WR99210 is a
      novel inhibitor of DHFR, effective even against the most pyrimethamine-resistant
      P. falciparum strains. We have found that it is also an extremely effective
      inhibitor of the P. vivax DHFR, and mutations that confer high-level resistance
      to pyrimethamine render the P. vivax enzyme exquisitely sensitive to WR99210.
      These data suggest that pyrimethamine and WR99210 would exert opposing selective
      forces on the P. vivax population. If used in combination, these two drugs could
      greatly slow the selection of parasites resistant to both drugs. If that is the
      case, this novel class of DHFR inhibitors could provide effective and affordable
      treatment for chloroquine- and pyrimethamine-resistant vivax and falciparum
      malaria for many years to come.

PMID- 12198182
TI  - Biosynthesis of terpenes: studies on 1-hydroxy-2-methyl-2-(E)-butenyl 4
      diphosphate reductase.
AB  - Earlier in vivo studies showed the involvement of IspH protein in the conversion
      of 1-hydroxy-2-methyl-2-(E)-butenyl 4-diphosphate into isopentenyl diphosphate
      (IPP) and dimethylallyl diphosphate (DMAPP). We have demonstrated now that cell
      extract of an Escherichia coli strain engineered for hyperexpression of the ispH
      (lytB) gene catalyzes the in vitro conversion of 1-hydroxy-2-methyl-2-(E)-butenyl
      4-diphosphate into IPP and DMAPP. The reaction requires NADH, FAD, divalent
      cations (preferably Co2+), and probably one or more as-yet-unidentified proteins.
      The low intrinsic catalytic activities of wild-type E. coli cell extract and
      isolated chromoplasts of red pepper (Capsicum annuum) are enhanced by the
      addition of purified recombinant IspH protein.

PMID- 12198183
TI  - Role of the C-terminal propeptide in the activity and maturation of gamma 
      interferon-inducible lysosomal thiol reductase (GILT).
AB  - gamma-Interferon-inducible lysosomal thiol reductase (GILT) is constitutively
      expressed in antigen-presenting cells. GILT facilitates unfolding of endocytosed
      antigens in MHC class II-containing compartments by enzymatically reducing
      disulfide bonds. The enzyme is synthesized as a 35-kDa precursor. Although a
      fraction of the precursor is secreted as a disulfide-linked dimer, the majority
      is directed via the mannose-6-phosphate receptor pathway to endocytic
      compartments where its N- and C-terminal propeptides are cleaved to generate the
      30-kDa mature form. Both precursor and mature GILT reduce disulfide bonds with an
      acidic pH optimum. In this report, we show that the cysteine residues in the C
      terminal propeptide, Cys-211 and Cys-222, serve key structural roles. Mutation of
      Cys-222 abolishes disulfide-linked dimerization of precursor GILT and decreases
      the efficiency of GILT maturation. Mutation of Cys-211 results in both impaired
      intracellular maturation and loss of enzymatic activity of the precursor form at
      an acidic pH. A similar phenotype was obtained upon mutation of Cys-200, which is
      retained in the mature form. Cys-200 and Cys-211 seem to form a disulfide bond
      that links the propeptide and the mature enzyme until reduction in the lysosome.
      This disulfide bridge is essential for stability of the enzyme at low pH and for
      its proper maturation in vivo.

PMID- 12198184
TI  - Evidence for van der Waals adhesion in gecko setae.
AB  - Geckos have evolved one of the most versatile and effective adhesives known. The
      mechanism of dry adhesion in the millions of setae on the toes of geckos has been
      the focus of scientific study for over a century. We provide the first direct
      experimental evidence for dry adhesion of gecko setae by van der Waals forces,
      and reject the use of mechanisms relying on high surface polarity, including
      capillary adhesion. The toes of live Tokay geckos were highly hydrophobic, and
      adhered equally well to strongly hydrophobic and strongly hydrophilic,
      polarizable surfaces. Adhesion of a single isolated gecko seta was equally
      effective on the hydrophobic and hydrophilic surfaces of a microelectro
      mechanical systems force sensor. A van der Waals mechanism implies that the
      remarkable adhesive properties of gecko setae are merely a result of the size and
      shape of the tips, and are not strongly affected by surface chemistry. Theory
      predicts greater adhesive forces simply from subdividing setae to increase
      surface density, and suggests a possible design principle underlying the
      repeated, convergent evolution of dry adhesive microstructures in gecko, anoles,
      skinks, and insects. Estimates using a standard adhesion model and our measured
      forces come remarkably close to predicting the tip size of Tokay gecko seta. We
      verified the dependence on size and not surface type by using physical models of
      setal tips nanofabricated from two different materials. Both artificial setal
      tips stuck as predicted and provide a path to manufacturing the first dry,
      adhesive microstructures.

PMID- 12198185
TI  - Aberrant expression of the light-inducible and circadian-regulated APRR9 gene
      belonging to the circadian-associated APRR1/TOC1 quintet results in the phenotype
      of early flowering in Arabidopsis thaliana.
AB  - Several Arabidopsis genes have been proposed to encode potential clock-associated
      components, including the Myb-related CCA1 and LHY transcription factors and a
      member (APRR1/TOC1) of the family of pseudo-response regulators. We previously
      showed that transcripts of the APRR1/TOC1 family genes each start accumulating
      after dawn rhythmically and sequentially at intervals in the order of APRR9-
      >APRR7-->APRR5-->APRR3-->APRR1/TOC1, under the conditions of continuous light.
      Nevertheless, no evidence has been provided that each member of the APRR1/TOC1
      quintet, except for APRR1/TOC1, is indeed relevant to the mechanisms underlying
      circadian rhythms. Here we attempt to provide such evidence by characterizing
      transgenic plants that aberrantly (or constitutively) express the APRR9 gene in a
      manner independent of circadian rhythms. The resulting APRR9-ox plants showed
      intriguing phenotypes with regard to circadian rhythms, in two aspects. First,
      the aberrant expression of APRR9 resulted in a characteristic phenotype with
      regard to transcriptional events, in which short-period rhythms were commonly
      observed for certain circadian-regulated genes, including CCA1, LHY, APRR1/TOC1,
      other APRR1/TOC1 members, ELF3, and CAB2. With regard to biological consequences,
      such APRR9-ox plants flowered much earlier than wild-type plants, in a manner
      independent of photoperiodicity (or under short-day conditions). These results
      suggest that APRR9 (and perhaps other members of the APRR1/TOC1 quintet) must
      also be taken into consideration for a better understanding of the molecular
      mechanisms underlying circadian rhythms, and also underlying control of the
      flowering time through the photoperiodic long-day pathway.

PMID- 12198186
TI  - Identification of K(+) channels in the plasma membrane of maize subsidiary cells.
AB  - The stomatal complex of Zea mays consists of two guard cells with the pore in
      between them and two flanking subsidiary cells. Both guard cells and subsidiary
      cells are important elements for stoma physiology because a well-coordinated
      transmembrane shuttle transport of potassium and chloride ions occurs between
      these cells during stomatal movement. To shed light upon the corresponding
      transport systems from subsidiary cells, subsidiary cell protoplasts were
      enzymatically isolated and in turn, analyzed with the patch-clamp technique.
      Thereby, two K(+)-selective channel types were identified in the plasma membrane
      of subsidiary cells. With regard to their voltage-dependent gating behavior, they
      may act as hyperpolarization-dependent K(+) uptake and depolarization-activated
      K(+) release channels during stomatal movement. Interestingly, the K(+) channels
      from subsidiary cells and guard cells similarly responded to membrane voltage as
      well as to changes in the K(+) gradient. Further, the inward- and outward
      rectifying K(+) current amplitude decreased upon a rise in the intracellular free
      Ca(2+) level from 2 nM to the micro M-range. The results indicate that the plasma
      membrane of subsidiary cells and guard cells has to be inversely polarized in
      order to achieve the anti-parallel direction of K(+) fluxes between these cell
      types during stomatal movement.

PMID- 12198187
TI  - The novel symbiotic phenotype of enhanced-nodulating mutant of Lotus japonicus:
      astray mutant is an early nodulating mutant with wider nodulation zone.
AB  - We have isolated a novel enhanced-nodulating mutant astray (Ljsym77) from Lotus
      japonicus. The name astray derives from the non-symbiotic phenotype of this
      mutant, agravitropic lateral roots that go "astray" against gravity. In this
      report we evaluated the symbiotic aspects of this mutant in detail. The astray
      mutant developed approximately twice the number of nodules on a wider area of
      roots compared with the wild type. Furthermore, the astray mutant demonstrated
      early initiation of nodule development, which is an unprecedented symbiotic
      phenotype. The astray seedlings showed normal sensitivity to the general
      inhibitors of nodulation such as ethylene and nitrate. These results indicate
      that the astray mutant is distinct from the hypernodulating mutants reported
      previously, and that the ASTRAY gene acts as an early and negative regulator in
      the cascade of nodule development.

PMID- 12198188
TI  - Blue light inactivates plasma membrane H(+)-ATPase in pulvinar motor cells of
      Phaseolus vulgaris L.
AB  - Unilateral blue light irradiation induces bending of pulvini of Phaseolus
      vulgaris towards the source of light. The pulvinar bending is caused by a
      decrease in turgor pressure of motor cells that are irradiated with blue light.
      Decrease in the turgor pressure is caused by the net efflux of K(+) and counter
      anions, accompanying membrane depolarization. In the present study the effect of
      blue light on the activity of plasma membrane H(+)-ATPase was studied in relation
      to the membrane depolarization. The activity of the plasma membrane H(+)-ATPase
      was measured using protoplast suspensions prepared from laminar pulvini from
      primary leaves. A pulse of blue light under continuous red light irradiation
      induced both a transient increase in the external pH and transient inhibition of
      the vanadate-sensitive ATPase. Continuous blue light irradiation under continuous
      red light irradiation induced both a sustained increase in the external pH and
      sustained inhibition of the vanadate-sensitive ATPase. These results show that
      blue light inhibits the activity of the plasma membrane H(+)-ATPase. Inactivation
      of the plasma membrane H(+)-ATPase supports the membrane depolarization induced
      by the blue light irradiation.

PMID- 12198189
TI  - Isolation and characterization of triacontanol-regulated genes in rice (Oryza
      sativa L.): possible role of triacontanol as a plant growth stimulator.
AB  - Triacontanol (TRIA) is a saturated long-chain alcohol that is known to have a
      growth promoting activity when exogenously supplied to a number of plants. In
      this study, dry weight, protein and chlorophyll contents of rice seedlings were
      increased by foliar application of TRIA. Leaf net photosynthesis rate (Pn) was
      increased very quickly and persistently at a given photon flux density (PFD). The
      TRIA-regulated genes in rice were isolated from cDNA library by differential
      screening with probes generated from the forward- and reverse-suppression
      subtractive hybridization (SSH) populations and confirmed by Northern blot.
      Sequence analysis revealed that most of the up-regulated genes encoded the
      photosynthetic and photorespiratory proteins. Two down-regulated genes were
      identified as those encoding an ABA- and stress-related protein and a wounding
      related protein. These results suggested that TRIA up-regulated the
      photosynthesis process and suppressed stresses in rice plants. Time-course
      profiles of expression of rbcS isogenes suggested the complex mechanisms involved
      in the regulation of photosynthesis promoted by TRIA.

PMID- 12198190
TI  - Contrasting effects of UV-A and UV-B on photosynthesis and photoprotection of
      beta-carotene in two Dunaliella spp.
AB  - Photosynthetic and antioxidant responses following exposure to either ultraviolet
      A or ultraviolet-B were contrasted in two species of the unicellular green alga,
      DUNALIELLA: Species selection was based on the ability of Dunaliella bardawil
      (UTEX 2538) to accumulate inter-thylakoid beta-carotene when subjected to
      environmental stress while Dunaliella salina (UTEX 200) lacks this ability. Cells
      were cultured in high and low levels of visible light (150 and 35 micro mol
      photons m(-2 )s(-1), respectively) and then either ultraviolet-A (320-400 nm) or
      ultraviolet-B (290-320 nm) was added to visible light for 24-h exposure. A
      potassium chromate solution was found to be an ideal screen for removal of
      ultraviolet-A and ultraviolet-C from ultraviolet-B radiation. There were no
      significant changes in photosynthetic or antioxidant parameters following
      exposure to ultraviolet-B. Ultraviolet-A exposure significantly decreased
      photosynthetic parameters (>70% decrease in Fv/Fm and the ratio of light-limited
      to light-saturated photosynthesis in low beta-carotene cells) and resulted in 50%
      increases in ascorbate peroxidase activity and ascorbate concentrations. The
      results suggest exposure to ultraviolet-A (but not ultraviolet-B) directly
      affects photosynthesis, observed as a loss of photosystem II electron transport
      efficiency and increased radical formation. This research indicates that the
      accumulated beta-carotene in D. bardawil prevents UV-related photosynthetic
      damage through blue-light/ultraviolet-A absorption (supported by trends observed
      for antioxidant enzyme responses).

PMID- 12198191
TI  - Functional analysis of water channels in barley roots.
AB  - We identified three genes homologous to water channels in the plasma membrane
      type subfamily from roots of barley seedlings. These genes were designated
      HvPIP2;1, HvPIP1;3, and HvPIP1;5 after comparison to Arabidopsis aquaporins.
      Competitive reverse transcription (RT)-PCR was applied in order to distinguish
      and to quantify their transcripts. The HvPIP2;1 transcript was the most abundant
      among the three in roots. Salt stress (200 mM NaCl) down-regulated HvPIP2;1
      (transcript and protein), but had almost no effect on the expressions of
      HvPIP1;3, or HvPIP1;5. Approximately equal amounts of the transcripts of the
      three were detected in shoots, and salt stress enhanced the expression of
      HvPIP2;1 but not of HvPIP1;3, or HvPIP1;5. HvPIP2;1 protein was confirmed to be
      localized in the plasma membrane. Functional expression of HvPIP2;1 in Xenopus
      oocytes confirmed that HvPIP2;1 encoded an aquaporin that transports water. This
      water permeability was reduced by HgCl(2), which is a typical water channel
      inhibitor. This activity was not modified by some inhibitors against protein
      kinase and protein phosphatase.

PMID- 12198192
TI  - High level expression of chorismate pyruvate-lyase (UbiC) and HMG-CoA reductase
      in hairy root cultures of Lithospermum erythrorhizon.
AB  - Shikonin, a red naphthoquinone pigment, is produced by cell cultures of
      Lithospermum erythrorhizon (Boraginaceae). It is biosynthetically derived from
      two key precursors, 4-hydroxybenzoate (4HB) and geranyldiphosphate (GPP). The
      bacterial ubiC gene, encoding chorismate pyruvate-lyase (CPL) which converts
      chorismate to 4-hydroxybenzoate, was expressed in L. erythrorhizon under the
      control of the strong (ocs)(3)mas-promoter. This introduced an efficient
      biosynthetic pathway to 4HB, i.e. a one-step reaction from chorismate, in
      addition to the endogeneous multi-step phenylpropanoid pathway. Feeding
      experiments with [1,7-(13)C(2)]shikimic acid showed that in the most active
      transgenic line, 73% of 4HB was synthesized via the genetically introduced
      pathway. However, there was no correlation between CPL activity and 4HB glucoside
      or shikonin accumulation in the transgenic lines. HMG-CoA reductase (HMGR) is
      involved in the biosynthesis of GPP in L. erythrorhizon. Two forms of HMGR1 of
      Arabidopsis thaliana were expressed in Lithospermum under control of the
      (ocs)(3)mas promoter. Only moderate increases in enzyme activity were obtained
      with the complete enzyme, but high activity was achieved using the soluble
      cytosolic domain of HMGR1. Shikonin accumulation remained unchanged even upon
      high expression of soluble HMGR.

PMID- 12198194
TI  - Hyperosmotic stress induces formation of tubulin macrotubules in root-tip cells
      of Triticum turgidum: their probable involvement in protoplast volume control.
AB  - Treatment of root-tip cells of Triticum turgidum with 1 M mannitol solution for
      30 min induces microtubule (Mt) disintegration in the plasmolyzed protoplasts.
      Interphase plasmolyzed cells possess many cortical, perinuclear and endoplasmic
      macrotubules, 35 nm in mean diameter, forming prominent arrays. In dividing cells
      macrotubules assemble into aberrant mitotic and cytokinetic apparatuses resulting
      in the disturbance of cell division. Putative tubulin paracrystals were
      occasionally observed in plasmolyzed cells. The quantity of polymeric tubulin in
      plasmolyzed cells exceeds that in control cells. Root-tip cells exposed for 2-8 h
      to plasmolyticum recover partially, although the volume of the plasmolyzed
      protoplast does not change detectably. Among other events, the macrotubules are
      replaced by Mts, chromatin assumes its typical appearance and the cells undergo
      typical cell divisions. Additionally, polysaccharidic material is found in the
      periplasmic space. Oryzalin and colchicine treatment induced macrotubule
      disintegration and a significant reduction of protoplast volume in every
      plasmolyzed cell type examined, whereas cytochalasin B had only minor effects
      restricted to differentiated cells. These results suggest that Mt destruction by
      hyperosmotic stress, and their replacement by tubulin macrotubules and putative
      tubulin paracrystals is a common feature among angiosperms and that macrotubules
      are involved in the mechanism of protoplast volume regulation.

PMID- 12198193
TI  - Expression of mangrove allene oxide cyclase enhances salt tolerance in
      Escherichia coli, yeast, and tobacco cells.
AB  - To analyze the mechanisms of salt tolerance in the mangrove plant, Bruguiera
      sexangula, functional screening for cDNAs encoding proteins essential for salt
      tolerance was performed using Escherichia coli as the host organism. A
      transformant expressing a protein homologous to Lycopersicon (tomato) allene
      oxide cyclase (AOC) displayed enhanced salt tolerance. However, this unusual
      trait is not conferred by Lycopersicon AOC or its Arabidopsis homolog. Analysis
      of the functional region revealed a sequence of only 70 amino acids, which
      contains an unusual sequence that is essential for the salt-tolerant phenotype.
      On the basis of its unusual function, the mangrove AOC homolog is designated
      "mangrin". Furthermore, expression of mangrin driven by the GAL1 promoter and the
      35S cauliflower mosaic virus (CaMV) promoter in Saccharomyces cerevisiae and
      tobacco cell lines, respectively, also gave rise to enhanced salt tolerance.
      Mangrin transcripts increased in cultured B. sexangula cells in response to salt
      stress. We propose that mangrin plays an important role in the salt-tolerance
      mechanism of B. sexangula, and that the biosynthesis of mangrin might be an
      effective means of enhancing salt tolerance in higher plants.

PMID- 12198195
TI  - AtMRD1 and AtMRU1, two novel genes with altered mRNA levels in the methionine
      over-accumulating mto1-1 mutant of Arabidopsis thaliana.
AB  - The mto1-1 mutant of Arabidopsis thaliana over-accumulates soluble methionine
      (Met) up to 40-fold higher than that in its Col-0 wild type. In order to identify
      genes regulated by altered Met concentrations, microarray analysis of gene
      expression in young rosettes and developing siliques of the mto1-1 mutant were
      performed. Expression of selected genes was then examined in detail in three
      developmental stages of the mto1-1 mutant using a combination of Northern
      hybridisation analysis and real-time PCR. Eight genes were identified that had
      altered mRNA accumulation levels in the mto1-1 mutant compared to that in wild
      type plants. Three of the genes have known roles in plant development unrelated
      to amino acid biosynthesis. One other gene up-regulated specifically in mto1-1
      rosettes shared similarity with the embryo-specific protein 3 (ATS3). Two novel
      genes, referred to as AtMRD1 and AtMRU1, were also identified that were expressed
      in a developmental manner in wild-type Col-0 and do not share sequence similarity
      with genes of known function. AtMRD1 was strongly down-regulated in both rosette
      and young silique tissues of the mto1-1 mutant. AtMRU1 was up-regulated
      approximately 3-fold in young mto1-1 rosettes and exhibited a developmental
      response to the mto1-1 mutation.

PMID- 12198196
TI  - Protection of the oxygen-evolving machinery by the extrinsic proteins of
      photosystem II is essential for development of cellular thermotolerance in
      Synechocystis sp. PCC 6803.
AB  - The oxygen-evolving machinery of photosystem II in cyanobacteria is associated
      with three extrinsic proteins: the manganese-stabilizing protein, cytochrome
      c(550), and PsbU. To elucidate the effect of the presence of these extrinsic
      proteins on the stabilization of the oxygen-evolving machinery against high
      temperature stress, we inactivated the genes for these proteins individually in
      Synechocystis sp. PCC 6803 by targeted mutagenesis. The thermal stability of the
      oxygen-evolving machinery decreased in all mutated cells but the extent of the
      susceptibility to heat inactivation varied between the photosystems lacking the
      different extrinsic proteins. Cells that lacked either the manganese-stabilizing
      protein or cytochrome c(550) were unable to enhance the thermal stability of the
      oxygen-evolving machinery and, moreover, failed to increase cellular
      thermotolerance when grown at moderately high temperatures. Our findings indicate
      that the three extrinsic proteins stabilize the oxygen-evolving machinery
      independently against high-temperature stress and that the thermal stability of
      the machinery influences cellular thermotolerance.

PMID- 12198197
TI  - Resistance of transgenic tobacco seedlings expressing the Agrobacterium
      tumefaciens C58-6b gene, to growth-inhibitory levels of cytokinin is associated
      with elevated IAA levels and activation of phenylpropanoid metabolism.
AB  - We previously reported that the Agrobacterium tumefaciens C58-6b gene confers
      resistance to growth-inhibitory levels of exogenously applied N(6)-benzyladenine
      (BA, cytokinin) in transgenic tobacco (Nicotiana tabacum) seedlings. Here, we
      found that intracellular levels of indoleacetic acid (IAA, auxin) increased in
      transgenics but declined in wild-type seedlings upon BA treatment. Since
      exogenously supplied 1-naphthalene acetic acid (NAA), a stable synthetic auxin,
      counteracted the growth inhibition of wild-type seedlings by BA, we suggest that
      BA-induced growth inhibition in wild-type seedlings occurs, at least in part, as
      a result of intracellular IAA deficiency. Further HPLC analysis of cell extracts
      from BA-treated seedlings revealed that a fluorescent compound, later identified
      as the phenylpropanoid, scopolin, and the major phenolic compound, chlorogenic
      acid, accumulated earlier in transgenics than in wild-type seedlings. Gene
      transcripts encoding phenylalanine ammonia-lyase, cinnamate 4-hydroxylase, and 4
      coumarate:CoA ligase, which are responsible for the early steps of
      phenylpropanoid biosynthesis, accumulated earlier and to higher levels in
      transgenics than in wild-type seedlings as determined by Northern hybridization
      analysis, thus accounting for the early accumulation of scopolin and chlorogenic
      acid in transgenics. As some phenolic compounds, including chlorogenic acid and
      scopoletin (aglycon of scopolin) are suggested to inhibit IAA catabolism, we
      further propose that C58-6b gene expression protects IAA from degradation by
      inducing the early phenylpropanoid pathway.

PMID- 12198199
TI  - Transcriptional regulation of a rice mitogen-activated protein kinase gene,
      OsMAPK4, in response to environmental stresses.
AB  - Mitogen-activated protein kinase (MAPK) cascades play important roles in signal
      transduction of extracellular stimuli in eukaryotes. However, stimulatory signals
      for plant MAPKs have not been well elucidated. Here, a cDNA clone, termed Oryza
      sativa MAPK4 (OsMAPK4), from rice encoding a protein that showed homology with
      the eukaryotic MAPKs was isolated. According to the phylogenetic analysis,
      OsMAPK4 belongs to subgroup IV MAPK in plants. OsMAPK4 transcripts were expressed
      strongly in mature leaves and weakly in young leaves and panicles. The gene was
      also differentially expressed in roots at different developmental stages. In
      addition, the mRNA level of OsMAPK4 was up-regulated under sugar starvation, high
      salinity and cold treatments. These results suggest that this OsMAPK4 functions
      not only in developmental programs but also in stress-signaling pathways.

PMID- 12198198
TI  - Cyclic electron flow within PSII functions in intact chloroplasts from spinach
      leaves.
AB  - Using thylakoid membranes, we previously demonstrated that accumulated electrons
      in the photosynthetic electron transport system induces the electron flow from
      the acceptor side of PSII to its donor side only in the presence of a pH gradient
      ((Delta)pH) across the thylakoid membranes. This electron flow has been referred
      to as cyclic electron flow within PSII (CEF-PSII) [Miyake and Yokota (2001) Plant
      Cell Physiol. 42: 508]. In the present study, we examined whether CEF-PSII
      operates in isolated intact chloroplasts from spinach leaves, by correlating the
      quantum yield of PSII [Phi(PSII)] with the activity of the linear electron flow
      [V(O(2))]. The addition of the protonophore nigericin to the intact chloroplasts
      decreased Phi(PSII), but increased V(O(2)), and relative electron flux in PSII
      [Phi(PSII) x PFD] and V(O(2)) were proportional to one another. Phi(PSII) x PFD
      at a given V(O(2)) was much higher in the presence of (Delta)pH than that in its
      absence. These effects of nigericin on the relationship between Phi(PSII) x PFD
      and V(O(2)) are consistent with those previously observed in thylakoid membranes,
      indicating the occurrence of CEF-PSII also in intact chloroplasts. In the
      presence of (Delta)pH, CEF-PSII accounted for the excess electron flux in PSII
      that could not be attributed to photosynthetic linear electron flow. The activity
      of CEF-PSII increased with increased light intensity and almost corresponded to
      that of the water-water cycle (WWC), implying that CEF-PSII can dissipate excess
      photon energy in cooperation with WWC to protect PSII from photoinhibition under
      limited photosynthesis conditions.

PMID- 12198200
TI  - The role of genetic susceptibility in diabetic nephropathy: evidence from family
      studies.

PMID- 12198201
TI  - A KQ121 variant in the PC-1 gene and diabetic nephropathy: discrepant results
      between North and South Europe.

PMID- 12198202
TI  - Why is blood pressure control unsatisfactory--or is it?

PMID- 12198203
TI  - Initiation of dialysis--is the problem solved by NECOSAD?

PMID- 12198204
TI  - Management of patients with advanced secondary hyperparathyroidism: the Japanese
      approach.

PMID- 12198205
TI  - Uraemic pruritus--new perspectives and insights from recent trials.

PMID- 12198206
TI  - Management of the infant with end-stage renal failure.

PMID- 12198207
TI  - Cyclosporine A up-regulates the expression of TGF-beta1 and its receptors type I
      and type II in rat mesangial cells.
AB  - BACKGROUND: Chronic cyclosporine A (CsA) nephropathy is a well described side
      effect of CsA treatment. CsA has been shown to induce the synthesis of
      extracellular matrix (ECM) proteins in mesangial cells (MCs) in vitro, and
      glomerulosclerosis in vivo. Transforming growth factor-beta1 (TGF-beta1) is a
      potent stimulus for the synthesis of ECM proteins in MCs. We investigated whether
      CsA up-regulates the expression of TGF-beta1 and its receptors type I (TbetaR-I)
      and type II (TbetaR-II) in cultured rat MCs, and whether this effect translates
      into enhanced matrix protein accumulation. METHODS: Resting MCs were incubated in
      the presence or absence of CsA and anti-TGF-beta1 antibodies. Time- and
      concentration-dependent expression of TGF-beta1, TbetaR-I and TbetaR-II were
      measured at both the mRNA (competitive reverse transcription PCR) and protein
      level (enzyme-linked immunosorbent assay (ELISA) and western blotting).
      Fibronectin (FN) and plasminogen activator inhibitor type-1 (PAI-1) synthesis
      were measured by ELISA. RESULTS: Compared with untreated controls, CsA stimulated
      mRNA production of TGF-beta1 (maximum at 72 h, 500 ng/ml CsA: 2.1+/-0.5-fold,
      P<0.001) and TbetaR-II (maximum at 72 h, 1000 ng/ml CsA: 2.4+/-0.4-fold, P<0.005)
      time- and dose-dependently. TbetaR-I mRNA concentrations remained unchanged.
      Protein concentrations were analysed at 96 h: TGF-beta1, 220+/-32 vs 86+/-24
      pg/ml, P<0.001 (500 ng/ml CsA vs control); TbetaR-I, 2.0+/-0.5-fold, P<0.005
      (1000 ng/ml CsA vs control); TbetaR-II, 2.5+/-0.7-fold, P<0.05 (1000 ng/ml CsA vs
      control). CsA (500 ng/ml) also enhanced the production of FN (1.6-fold, P<0.05)
      and PAI-1 (2.0-fold, P<0.05). Co-incubation with neutralizing anti-TGF-beta1
      antibodies reduced (P<0.05) CsA-induced expression of TbetaR-I (1.0+/-0.1-fold),
      TbetaR-II (1.3+/-0.1-fold) and PAI-1 (1.3-fold), but not FN production (1.6
      fold). CONCLUSIONS: Pharmacologically relevant concentrations of CsA time- and
      dose-dependently up-regulate the expression of TGF-beta1 and, via autocrine
      mechanisms, its receptors type I and II in rat MCs. Whereas up-regulation of PAI
      1 is mediated by TGF-beta1, up-regulation of FN is-at least in part-either
      directly induced by CsA or mediated by factors other than TGF-beta1.

PMID- 12198208
TI  - The effect of endothelin antagonists on renal ischaemia-reperfusion injury and
      the development of acute renal failure in the rat.
AB  - BACKGROUND: It is recognized that endothelins are released in response to
      hypoperfusion and anoxia of the kidney and may be responsible for the consequent
      deterioration in renal function. This study examined the ability of a non
      selective (SB209670) and ET(A)-selective (UK-350,926) endothelin antagonist to
      attenuate ischaemia-induced renal failure in unilaterally nephrectomized rats.
      METHODS: The animals were anaesthetized, drug infusion commenced, and the renal
      artery occluded for 30 min. The endothelin antagonists were given for 30 min
      before, during, and 60 min after the ischaemic period, at 10, 30 and 100 micro
      g/kg/min or for 60 min after the start of reperfusion. RESULTS: On day 1,
      following 30 min renal artery occlusion, there was a 95% reduction in glomerular
      filtration rate, an 8-10-fold increase in plasma creatinine, and 10-15-fold
      increases in fractional excretions of sodium and potassium, which were partially
      resolved on day 3 and normalized on day 8. The lowest dose of SB209670 was
      without effect on the renal functional responses but they were blunted (all
      P<0.05) by the highest dose. At 30 and 100 micro g/kg/min UK-350,926, the
      decreases in renal function subsequent to the ischaemic challenge were
      attenuated. Administration of UK-350,926 at 100 micro g/kg/min for 1 h starting
      60 min after the start of reperfusion, had no effect on the magnitude of the
      renal disturbances over the first 3 days. CONCLUSIONS: The data show that both
      the ET(A)/ET(B) and selective ET(A)-receptor antagonist ameliorated the ischaemia
      reperfusion injury when given in the peri-ischaemic period but not when the ET(A)
      receptor antagonist was given for 60 min at 100 micro g/kg/min after the
      ischaemic period.

PMID- 12198209
TI  - Glomerular changes in microscopic haematuria, studied by quantitative
      immunoelectron microscopy and in situ zymography.
AB  - BACKGROUND: Haematuria of glomerular origin, even if mild, implies the
      development of defects in the glomerular basement membrane (GBM). In diseases
      where there is no infiltration of leukocytes into the glomerulus-such as thin
      basement membrane disease (TBMD) and histologically mild cases of IgA nephropathy
      (IgAN)-the mechanism by which such defects form is unclear. METHODS: Frozen renal
      tissue from 18 cases of TBMD, 18 of mild IgAN and 18 cases with no detectable
      abnormality were studied: (i) by quantitative in situ zymography, to estimate the
      activity of glomerular collagenases; and (ii) by quantitative immunoelectron
      microscopy to estimate the amount of major basement membrane proteins per unit
      length and per unit area of glomerular basement membrane. RESULTS: Cases of IgAN
      showed considerably more glomerular collagenase activity than normal (P=0.001).
      Thin basement membrane disease showed no difference in collagenase activity. A
      count of LCA-positive cells in glomeruli confirmed that the IgAN cases did not
      show glomerular leukocyte infiltration. Conversely, cases of IgAN showed no
      difference in GBM composition from normal, nor was any difference in GBM
      thickness detected in this group. However, cases of TBMD showed considerably less
      laminin (P=0.0008), fibronectin (P=0.002) and type VI collagen (P=0.0005) per
      unit length of basement membrane. Collagen IV showed a smaller reduction per unit
      length (P=0.01), but unlike the other protein studies it appeared to be present
      in higher concentration per unit area (P=0.03), suggesting that it is more
      'compact' in TBMD disease. CONCLUSIONS: Two distinct mechanisms of haematuria
      seem to be involved in these two conditions. In IgAN there is increased activity
      of enzymes that can degrade GBM, probably reflecting mesangial cell activation.
      In TBMD an abnormal composition of the thinned GBM is confirmed. When considered
      with published reports of genetic abnormalities in TBMD, these results raise the
      possibility of an abnormal interaction between collagen IV and laminin.

PMID- 12198210
TI  - Frequency of renal pathology in Spain 1994-1999.
AB  - BACKGROUND: There are not enough large epidemiological population-based studies
      of biopsy-proven nephropathies with detailed clinical and histopathological data.
      METHODS: The Glomerulonephritis Registry of the Spanish Society of Nephrology has
      obtained data from 7016 patients with biopsied renal diseases between 1994 and
      1999, investigating prevalence, incidence and clinical and histopathological
      data. Biopsies of transplant kidneys have not been considered. RESULTS: The
      observed biopsy rate for all ages is 4.8 per 100 000 inhabitants. A male
      predominance is seen for all age groups. The most common clinical syndrome at any
      age is nephrotic syndrome. The prevalence of hypertension is higher in adults and
      elderly patients. The most common pathologies are IgA nephropathy, focal
      glomerulosclerosis, membranous nephropathy and lupus nephritis. The mean annual
      incidence (per million of population) of the most common nephropathies is IgA
      nephropathy 7.9, focal segmental glomerulosclerosis 6.4, membranous nephropathy
      6.2, lupus nephritis 5.6, minimal-change disease 4.8, nephroangiosclerosis 4.6,
      vasculitis 4.3, membranoproliferative glomerulonephritis 3.6 and amyloidosis 3.3.
      In children, the most frequent causes are minimal-change disease, IgA nephropathy
      and focal glomerulosclerosis. In adults, the most common diagnoses are IgA
      nephropathy, lupus nephritis, and focal glomerulosclerosis. In elderly patients,
      the most frequently reported pathologies are vasculitis, membranous nephropathy
      and amyloidosis. Membranous nephropathy has increased in incidence in recent
      years. CONCLUSIONS: We provide representative population-based descriptive data
      on native biopsy-proven renal diseases in Spain.

PMID- 12198211
TI  - Prognostic factors in mesangioproliferative glomerulonephritis.
AB  - BACKGROUND: The aim of our study was to examine patients with
      mesangioproliferative glomerulonephritis (MPGN), with or without glomerular IgA
      deposits, and to analyse the effect of different clinical and histopathological
      variables at the time of biopsy on progression to end-stage renal failure (ESRF)
      and death. METHODS: We retrospectively examined 273 patients who got this
      diagnosis in Norway from April 1988 to December 1990 after a renal biopsy. All
      patients were followed for a median duration of 34.8 months (0.8-68 months).
      RESULTS: The mean age at the time of biopsy was 40+/-17 years (range 1.1-79
      years). Glomerular IgA deposits were present in 45% of the patients; IgA deposits
      did not affect prognosis. Three years after the time of biopsy, 7% had developed
      ESRF (chronic dialysis treatment or kidney transplantation) and 8% had died. By
      Kaplan-Meier analyses, the following clinical variables indicated progression to
      ESRF: increased serum creatinine, proteinuria > or =1 g/24 h, systolic blood
      pressure (BP) > or =160 mmHg, diastolic BP > or =90 mmHg, serum albumin <35 g/l,
      presence of urinary granular casts and age > or =60 years. Morphological
      variables indicating progression to ESRF were presence of focal mesangial
      sclerosis, focal glomerular crescents or necroses, benign nephrosclerosis and
      increased interstitial score. In the multivariable analysis, the following
      variables indicated progression to ESRF: increased serum creatinine (P<0.001),
      decreased serum albumin (P<0.05), increased diastolic BP (P<0.05), low age
      (P<0.05) and increased interstitial score (P<0.001). CONCLUSIONS: It is possible
      from clinical and histopathological variables to identify low-risk and high-risk
      patients at the time of biopsy. There is, however, considerable convergence. A
      major new observation is the finding of young age, decreased serum albumin and
      the presence of urinary granular casts as important clinical risk factors.
      Interstitial damage was the most important histopathological predictor of ESRF.

PMID- 12198212
TI  - Epithelial Ca(2+) channel (ECAC1) in autosomal dominant idiopathic
      hypercalciuria.
AB  - BACKGROUND: The epithelial Ca(2+) channel (ECaC) exhibits the defining properties
      for being the gatekeeper in 1,25-dihydroxyvitamin D(3)-regulated Ca(2+)
      (re)absorption. Its recently cloned human orthologue (ECaC1) could, therefore,
      represent a crucial molecule in human disorders related to Ca(2+)-wasting such as
      idiopathic hypercalciuria (IH). METHODS: Fifty-seven members of nine families
      with IH were investigated. Phenotyping was performed by measurements of urinary
      Ca(2+) excretion, while other underlying disorders were appropriately excluded.
      Initially, the recently suggested locus for kidney stone-associated
      hypercalciuria on chromosome 1q23.3-q24 was investigated. Next, direct mutation
      analysis of all 15 exons of the ECAC1 gene and 2.9 kb upstream from the start
      codon was performed. hECaC1, heterologously expressed in human embryonic kidney
      293 cells, was characterized by patch-clamp analysis. RESULTS: The mode of
      inheritance in the studied pedigrees is consistent with an autosomal dominant
      trait. Haplotype analysis did not implicate a role of the locus on chromosome 1.
      The coding sequence of the ECAC1 gene was not different between the affected and
      the non-affected family members. In the 5'-flanking region, three single
      nucleotide polymorphisms were encountered, but these polymorphisms were observed
      regardless of the affection status of the screened family members. Patch-clamp
      analysis of hECaC1 was performed as the putative pore region contains four non
      conserved amino acid substitutions compared with the other species. This analysis
      revealed the distinctive properties of ECaC, including a high Ca(2+) selectivity,
      inward rectification, and Ca(2+)-dependent inactivation. CONCLUSION: These
      results do not support a primary role for hECaC1 in IH in nine affected families.
      Because of the heterogeneity of the disease, however, the involvement of ECaC1 in
      other subtypes of IH cannot be excluded and needs further investigation. The
      electrophysiological properties of hECaC1 further substantiate its prime role in
      Ca(2+) (re)absorption.

PMID- 12198213
TI  - Incidence of anaemia, and use of epoetin therapy in pre-dialysis patients: a
      prospective study in 403 patients.
AB  - BACKGROUND: Recent American and European guidelines recommend that epoetin
      therapy should be considered whenever the blood haemoglobin (Hb) level is <10-11
      g/dl in dialysis patients and in pre-dialysis patients. Thus, data on the current
      prevalence of anaemia with respect to the degree of chronic renal insufficiency
      are needed in order to determine the potential indications of epoetin therapy in
      the pre-dialysis period. METHODS: We prospectively studied 403 consecutive
      ambulatory pre-dialysis patients whose serum creatinine (Scr) was 200 micro mol/l
      or more at their first passage at our out-patient clinic between January 1 and
      June 30, 1999. Hb and Scr values were determined at each visit until June 30,
      2000, or until the start of maintenance dialysis. Patients had a clinical and
      laboratory evaluation every 2-3 months, and monthly when treated with epoetin.
      RESULTS: The mean (+/-SD) age of patients was 60.9+/-17.2 years at presentation.
      The Hb level was <11 g/dl in 62% of patients with Scr > or =400 micro mol/l, and
      in 58% of patients with an estimated creatinine clearance (Ccr) <20 ml/min/1.73
      m(2). The proportion of anaemic patients was higher for any given Ccr value in
      females than in males. A total of 136 patients were treated with epoetin during
      the observation period. At the start of epoetin, their mean Hb value was 9.5+/
      0.6 g/dl and Ccr level 13.9+/-4.9 ml/min/1.73 m(2). Among the 123 patients who
      began maintenance dialysis therapy during the observation period, 85 (or 69%)
      received epoetin therapy before the start of dialysis. Their mean Hb value at the
      start of dialysis was 10.8+/-1 g/dl compared with 10.5+/-1.1 g/dl in the 41
      dialysed patients who did not require epoetin therapy during the pre-dialysis
      period. CONCLUSIONS: Based on the data gained in a large cohort of patients
      receiving regular pre-dialysis nephrological care, the proportion of subjects
      with a Hb level <11 g/dl may be estimated at approximately 60% when the Ccr is
      <20 ml/min/1.73 m(2). If the Hb level is to be maintained at no less than 11
      g/dl, at least two-thirds of patients at this advanced stage of chronic renal
      failure should require pre-dialysis epoetin therapy.

PMID- 12198214
TI  - The contradiction of stable body mass despite low reported dietary energy intake
      in chronic haemodialysis patients.
AB  - BACKGROUND: Dietary energy intake (DEI) is reported to be below recommended
      values in a large proportion of stable chronic haemodialysis patients, while
      energy requirement appears not to be very different from that in healthy
      subjects. Nevertheless, body mass has often been reported to be stable over time.
      We hypothesized that underestimation of habitual DEI by self-reporting of food
      intake could explain the contradiction of a neutral energy balance despite an
      apparently insufficient DEI. METHODS: In a group of 38 adequately dialysed
      haemodialysis patients the values of self-reported DEI and body mass assessed by
      anthropometry were analysed over a 40-week study period. In the total group, body
      mass increased over time at a DEI of 29+/-5 kcal/kg of desirable body weight per
      day. Self-reported DEI was factored by an estimate of the patient's basal
      metabolic rate (BMR) to arrive at a DEI/BMR ratio. A total energy expenditure
      (TEE) of at least 1.27 times the BMR is presumed to be required to maintain body
      weight over time. A DEI that is lower than this minimum value of TEE in patients
      with stable body mass over time strongly suggests underreporting of habitual DEI.
      RESULTS: In 61% of the patients the DEI/BMR ratio was below 1.27. In these
      patients, body weight increased significantly over time, despite a DEI/BMR ratio
      of only 1.06+/-0.15. Body mass index correlated inversely with total DEI (r=
      0.39, P<0.05) and the DEI/BMR ratio (r=-0.60, P<0.001), indicating that self
      reported DEI was lowest in overweight patients. CONCLUSIONS: These observations
      suggest that the contradiction of a stable body mass over time despite an
      apparently insufficient DEI in haemodialysis patients is mainly explained by an
      underestimation of habitual DEI from self-reported food intake.

PMID- 12198215
TI  - Effects of haemodialysis on maximum P wave duration and P wave dispersion.
AB  - BACKGROUND: Analysing a 12-lead surface electrocardiogram (ECG), the inter-lead
      variability of the P wave interval, i.e. P wave dispersion, is defined as the
      difference between the maximum and the minimum P wave duration. Our aim was to
      assess the effect of haemodialysis on P wave duration and dispersion in non
      diabetic patients with end-stage renal failure on chronic haemodialysis. METHODS:
      Twenty-eight patients (14 men and 14 women, mean age 58+/-16 years, average
      duration of dialysis 4.5+/-2.8 years) were examined. Prior to haemodialysis,
      echocardiography (M-mode and two-dimensional) was performed. Haemodialysis
      sessions were carried out with polysulfone dialysers and bicarbonate dialysate
      fluids. Twelve-lead ECGs were recorded at the beginning, 15 and 30 min after
      starting dialysis, at the end, and 2 h after completion of each session. Ionic
      parameters were checked during the study. P wave durations were measured with
      calipers in three consecutive complexes of each lead by one observer. RESULTS: P
      maximum was 58+/-16 ms at the beginning, and showed an increase by the end of
      dialysis to 98+/-8.9 ms (P<0.0001). Pre-dialysis P dispersion was 23+/-10 ms and
      increased to 41+/-16 ms by the end of the sessions (P<0.0001). In patients with a
      left atrial diameter larger than 45 mm, P dispersion increased from 23+/-11 to
      53+/-10 ms (P<0.0003) by the end of the sessions. CONCLUSIONS: According to our
      results, ionic imbalance and dialysis itself may cause changes in P duration and
      dispersion simultaneously.

PMID- 12198216
TI  - Electrocardiography is unreliable in detecting potentially lethal hyperkalaemia
      in haemodialysis patients.
AB  - BACKGROUND: It is speculated, but unconfirmed, that the usual
      electrocardiographic manifestations of hyperkalaemia are less frequent and less
      pronounced in persons with end-stage renal disease (ESRD) than in those with
      normal renal function. We studied 74 consecutively selected stable haemodialysis
      patients to determine the prevalence of electrocardiographic changes of
      hyperkalaemia in stable persons with ESRD receiving haemodialysis. METHODS: Pre
      dialysis serum potassium concentration and other electrolytes were measured and
      simultaneous 12-lead electrocardiogram obtained. RESULTS: The 74 study subjects
      (45 men, 29 women) comprised 63 blacks (85%), four Hispanics (6%), four whites
      (6%), and three Asians (4%) of mean+/-standard deviation age 55.5+/-14.7 years.
      Mean pre-dialysis potassium concentration was 4.9+/-0.71 mEq/l (range 3.3-6.7).
      No study subject evinced arrhythmia or any of the typical electrocardiographic
      changes associated with hyperkalaemia. There was no significant difference in T
      wave amplitude (F statistic=2.1; P=0.11) or T wave to R wave ratio (F
      statistic=2; P=0.12) between quartiles of serum potassium concentration. Also, T
      wave amplitude was equivalent in patients with serum potassium concentration >5.5
      mEq/l (7.1+/-4.1 mm) or < or =5.5 mEq/l (5.2+/-3.5 mm) (P=0.13). Linear
      regression analysis showed that the total serum calcium concentration had an
      inverse relation with T wave amplitude (P=0.03) after adjustment for other
      factors (a high total serum calcium concentration was associated with a low T
      wave amplitude). CONCLUSION: Haemodialysis patients with hyperkalaemia may not
      exhibit the usual electrocardiographic sequella of hyperkalaemia, possibly due in
      part to fluctuations in serum calcium concentration. Thus, the absence of
      electrocardiographic changes in hyperkalaemic haemodialysis patients should be
      interpreted with caution.

PMID- 12198217
TI  - A prospective study of combination therapy for hyperphosphataemia with calcium
      containing phosphate binders and sevelamer in hypercalcaemic haemodialysis
      patients.
AB  - INTRODUCTION: Hyperphosphataemia is predictive of death, in haemodialysis (HD)
      patients. Sevelamer is a mineral-free phosphate binder not limited by the
      hypercalcaemia often encountered when utilizing calcium-containing phosphate
      binders. Highly positive calcium balance is associated with ectopic calcification
      and potentially accelerated vascular disease. Unfortunately, exclusive use of
      sevelamer entails a large cost differential, limiting its use in many centres. We
      report on a strategy of partial replacement of calcium with sevelamer for the
      management of hyperphosphataemia in hypercalcaemic chronic HD patients. METHODS:
      We identified 23 HD patients with serum calcium >2.6 mmol/l. Dietary phosphate
      and calcium intake were assessed and baseline serum calcium, phosphate and 1alpha
      calcidol and elemental calcium dose recorded. Fifty per cent of this initial
      calcium dose was exchanged for sevelamer. Vitamin D doses were left unchanged. If
      serum calcium was still >2.6 mmol/l after 4 weeks a further 50% of calcium was
      exchanged. If serum phosphate was >2 mmol/l the sevelamer dose was increased by
      25%. The patients were followed up for a further 4 weeks. RESULTS: Seven patients
      complained of gastrointestinal intolerance of sevelamer. Serum calcium fell from
      a mean value of 2.8+/-0.04 (2.64-3.54) mmol/l to 2.56+/-0.03 (2.4-2.9) mmol/l,
      P<0.0005. The hypercalcaemic percentage of patients fell from 100 to 26%. Mean
      serum phosphate was not significantly changed, 1.59+/-0.1 (0.57-2.6) mmol/l to
      1.63+/-0.11 (0.55-2.68) mmol/l, 17-22% of patients having serum phosphate >2
      mmol/l. Serum intact parathyroid hormone increased from 166+/-47 (12-933) ng/l to
      276+/-104 (20-1013) ng/l, P=0.02. Mean sevelamer dose was 2.77+/-0.36 (0-5.6) g
      per day. Elemental calcium dose fell from 2.05+/-0.23 (0.5-4.5) g to 1.03+/-0.1
      (0.5-2.5) g, P<0.0001. CONCLUSION: A regimen based on the combination of
      sevelamer and calcium is capable of effectively managing hyperphosphataemia,
      without hypercalcaemia, in the majority of hypercalcaemic HD patients. Such a
      minimally calcaemic approach might reduce the financial burden of sevelamer
      therapy, and enable a wider range of patients to be treated.

PMID- 12198218
TI  - CAHP-210 dialyzer influence on intra-dialytic vancomycin removal.
AB  - BACKGROUND: Vancomycin is often administered during the last hour of
      haemodialysis because it was not removed significantly by older hemodialyzers.
      However, newer higher permeability hemodialyzers remove vancomycin, although the
      amount removed varies considerably between dialyzers. The purpose of this study
      was to determine the apparent amount of vancomycin removed during the last hour
      of haemodialysis with a CAHP-210 hemodialyzer. METHODS: Eight subjects with end
      stage renal disease (ESRD) received i.v. vancomycin 15 mg/kg after their regular
      haemodialysis session ended. Serum samples for the determination of vancomycin
      concentrations were obtained serially for 44 h. After a 3-week washout, the study
      was repeated with the vancomycin infused during the last hour of their regular
      haemodialysis session using a CAHP-210 hemodialyzer. Vancomycin concentrations
      were determined by the Enzyme Multiplied Immunoassay Technique. Differential
      equations describing a two-compartment open infusion model were fitted to the
      serum concentration vs time data and pharmacokinetic parameters and apparent
      vancomycin removal was estimated. RESULTS: The median age and weight of the
      subjects were 52 years (range 37-71) and 75.6 kg (range 37.6-89.8), respectively.
      The apparent vancomycin intra-dialytic removal was 0.24 (range -0.07-0.35), which
      was statistically significantly different from zero. CONCLUSIONS: Vancomycin
      administered during the last hour of CAHP-210 dialysis results in 24% less
      vancomycin exposure than when administered post-haemodialysis. This intra
      dialytic drug loss should be accounted for when dosing vancomycin in this manner.

PMID- 12198219
TI  - Patient-related and centre-related factors influencing technique survival of
      peritoneal dialysis in The Netherlands.
AB  - BACKGROUND: Although technique failure occurs relatively frequently in peritoneal
      dialysis (PD), few data have been published on differences in technique failure
      between centres. METHODS: Using data from RENINE, the comprehensive dialysis
      registry of The Netherlands, we analysed PD technique failure rates in the period
      1994-1999, with life table methods and Cox multiple regression analysis. Patient
      age, sex, and the presence or absence of diabetes were included in the analysis,
      as well as time of initiation of PD and the following centre characteristics:
      number of PD patients treated in the centre and percentage of patients on PD.
      RESULTS: Technique failure was higher in older patients: 2-year technique
      survival was 75% in those younger than 45 years, 68% in the group aged 45-64
      years, and 60% in those over 64 years (P<0.0001). Sex and diabetes made no
      difference in technique survival. Mean annual technique failure rates varied
      greatly between centres (10-59%) and correlated with the number of patients on PD
      in the centre (r=-0.396, P=0.009) and with the fraction of patients on PD (r=
      0.410, P=0.006). Low technique survival rates occurred mainly in centres with
      less than 20 patients on PD: relative risk for technique failure 1.68 as compared
      with larger centres. Patients starting PD in the period 1997-1999 had better
      technique survival than those starting in 1994-1996 (P=0.001). CONCLUSION: PD
      technique survival in The Netherlands has increased in recent years. Having less
      than 20 PD patients in a centre or having a small fraction of patients on PD
      carries an increased risk of technique failure. The variability in PD technique
      survival between centres indicates that in many centres further improvements
      should be possible.

PMID- 12198220
TI  - Uncontrolled hypertension due to volume overload contributes to higher left
      ventricular mass index in CAPD patients.
AB  - BACKGROUND: Hypertension (HT) is common in patients on continuous ambulatory
      peritoneal dialysis (CAPD) and is responsible for increased cardiovascular
      morbidity and mortality. In this study, we aimed to determine the prevalence of
      'uncontrolled HT' during background therapy in CAPD patients by using office
      measurements and ambulatory blood pressure monitoring (ABPM). We further
      determined whether intravascular volume status, assessed by inferior vena cava
      diameter (IVCD) index, contributes to higher blood pressure (BP) and increased
      left ventricular mass index (LVMI). METHODS: Seventy-four CAPD patients were
      included in the final analysis. All patients underwent echocardiographic
      examination and received ABPM. Patients undergoing CAPD were categorized into two
      groups: 'uncontrolled HT' (Group A) and 'normotensive and controlled HT' (Group
      B). Intravascular volume status was determined using the IVCD index and
      collapsibility index (CI) on the same day as ABPM. RESULTS: The prevalence of HT
      was 84% when using office measurements and 82% when using daytime ABPM. Daytime
      BP was 147/92 mm Hg by office measurements and 145/91 mm Hg by ABPM (P>0.05). The
      prevalence of 'uncontrolled HT' measured by ABPM was 73% (n=54). Patients with
      uncontrolled HT (Group A) were taking more antihypertensive medications than
      patients with 'normotension and controlled HT' (Group B, n=20; 1.0+/-0.8 vs 0.5+/
      0.7, P=0.008). The IVCD index was higher in Group A than in Group B (9.2+/-2.1 vs
      7.7+/-1.9 mm/m(2), P=0.007). There was no correlation between IVCD index and
      office BP, ABPM measurements or LVMI. The LVMI was also higher in Group A than in
      Group B (145+/-39 vs 118+/-34 g/m(2), P<0.01). Stepwise multiple regression
      analysis revealed that 24 h diastolic BP and haemoglobin were independent
      determinants of LVMI. CONCLUSION: Uncontrolled HT on background therapy is highly
      prevalent among volume overloaded CAPD patients. Further long-term prospective
      studies examining effects of salt restriction and ultrafiltration on BP control
      and left ventricle wall thickness are warranted.

PMID- 12198221
TI  - Erythropoietin therapy may retard progression in chronic renal transplant
      dysfunction.
AB  - BACKGROUND: Recent data suggests that erythropoietin therapy may actually retard
      the progression of chronic kidney disease (CKD). Transplant recipients with
      evidence of chronic allograft dysfunction could respond in a similar manner to
      erythropoietin. METHODS: We evaluated 166 individuals who initiated
      erythropoietin therapy after at least 18 days of transplant function. One hundred
      and nine individuals received erythropoietin between days 18 and 294 of
      transplant function (group 1-early epoietin alfa) while 57 individuals received
      erythropoietin on or after day 294 of transplant function (group 2-late epoietin
      alfa). The slope of serum creatinine (Scr) (Deltaslope Scr) prior to and
      following the start of erythropoietin therapy and calculated glomerular
      filtration rates (GFR) were used to assess renal function over time. RESULTS: The
      average haematocrit rose 6.6% in group 1 patients and 2.1% in group 2 patients
      during the first 100 days of erythropoietin therapy. The Deltaslope Scr was not
      significantly altered in group 1 patients. However, for group 2 individuals who
      continued to have graft function (n=35), the Deltaslope Scr became negative
      during erythropoietin treatment. This indicated a deceleration in the rate of
      loss of renal function (day 200 Deltaslope Scr -0.0033, P=0.00091; day 300
      Deltaslope Scr -0.0014, P=0.05; day 400 Deltaslope Scr -0.0066, N.S., P=0.066).
      GFR remained stable in both cohorts. Finally, group 2-late epoietin alfa patients
      treated with erythropoietin demonstrated a marked trend towards longer graft
      survival than a group of similar control patients (N.S., P=0.064). CONCLUSIONS:
      The data in a group of renal transplant recipients with chronic allograft
      dysfunction reinforce data from the CKD realm suggesting that erythropoietin may
      be of benefit in slowing the rate of loss of function over time. However, this
      renal response is not evident in all patients. Prospective studies of
      erythropoietin or erythropoietin-like medications are warranted in this
      population to better discriminate those who may respond well to administration of
      these drugs.

PMID- 12198222
TI  - Homocysteine, nutritional status and insulin in renal transplant recipients.
AB  - BACKGROUND: Hyperhomocysteinemia is an independent risk factor for the
      development of cardiovascular conditions in chronic stable renal-transplant
      recipients (RTR). Major determinants of plasma total homocysteine (tHcy) in RTR
      are renal function and folate levels. The data dealing with the possible
      regulation of the tHcy metabolism by insulin and nutritional status is
      conflicting in non-transplant populations. METHODS: We examined the relationship
      between tHcy, insulin and nutritional status in 103 chronic, stable RTR.
      Demographic, clinical, and biochemical parameters were assessed for each patient.
      RESULTS: Mean tHcy was 19.7+/-9.2 micro mol/l (range 8.6-53). The tHcy was
      strongly related to creatinine clearance (r=0.55, P<0.0001). Fasting tHcy levels
      were negatively related to folate concentrations (r=-0.32, P=0.01). There was a
      positive relationship between tHcy and LDL-cholesterol (r=0.34, P=0.03) and a
      significant negative correlation between tHcy and insulin (r=-0.38, P=0.01).
      Fasting tHcy concentrations were significantly higher in the lower quartile of
      insulin concentration than in the upper quartile (27.7+/-12.7 vs 15.9+/-9.5,
      P=0.01). In multivariate analysis, tHcy was associated with serum creatinine
      (P=0.001), insulin (P=0.02) and folate concentration (P=0.03). Patients with the
      highest IGF-1 concentration had lower tHcy than patients with the lowest IGF-1
      concentration (16.8+/-5.7 vs 23.3+/-11 micro mol/l, P=0.01). CONCLUSION: We
      observed an inverse relationship between insulin and tHcy in chronic, stable RTR.

PMID- 12198223
TI  - Kidney transplantation in type 2 diabetic patients: a comparison with matched non
      diabetic subjects.
AB  - BACKGROUND: Because they generally are older and frequently have co-morbidities,
      patients with type 2 diabetes mellitus and end-stage renal disease seldom are
      selected for renal transplantation. Thus, information on transplantation results
      from controlled studies in this high-risk category of patients is scarce. We have
      compared the results of kidney transplantations in type 2 diabetic patients with
      carefully matched non-diabetic subjects. METHODS: All first cadaveric renal
      transplants performed in type 2 diabetic patients from January 1, 1988 to
      December 31, 1998 in our centre were included. Non-diabetic controls were
      individually matched with diabetic patients with respect to year of
      transplantation, sex, age, selected immunological parameters, and graft cold
      ischaemia. RESULTS: We included 64 type 2 diabetic and 64 non-diabetic patients
      who were followed for a mean period of 37+/-27 and 41+/-31 months, respectively,
      after renal transplantation. Patient survival at 1 and 5 years post-transplant
      was 85 and 69 vs 84 and 74% (P=0.43, NS), while graft survival rates censored for
      patient death were 84 and 77 vs 82 and 77% for diabetic and non-diabetic
      subjects, respectively (P=0.52, NS). With graft survival results not censored for
      death with functioning graft, no significant change was seen (diabetic vs non
      diabetic group: 77 and 54 vs 73 and 61%, P=0.19, NS). Age, but not the presence
      of diabetes, was the only factor significantly affecting patient survival when
      both patient groups were pooled. With regard to post-transplant complications
      requiring hospitalization, there was a significant difference only in the number
      of patients who had amputations (diabetic vs non-diabetic group: 8 vs 0, P=0.01).
      CONCLUSIONS: Patient and graft survival after kidney transplantation was similar
      in type 2 diabetic and matched non-diabetic subjects, with more amputations
      occurring in the diabetic group. Thus, at a single-centre level renal
      transplantation results almost equivalent to those in non-diabetic patients may
      be achieved in type 2 diabetes mellitus.

PMID- 12198225
TI  - Efficacy of haemodiafiltration treatment with PEPA dialysis membranes in plasma
      free light chain removal in a patient with primary amyloidosis.

PMID- 12198224
TI  - Interleukin-6 is an independent predictor of mortality in patients starting
      dialysis treatment.
AB  - BACKGROUND: The mortality rate is high among end-stage renal disease (ESRD)
      patients, and recent evidence suggests that this may be linked to inflammation.
      The activity of interleukin-6 (IL-6) and its soluble receptor (sIL-6R) are
      markedly up-regulated in ESRD patients, and plasma IL-6 levels predict outcome in
      haemodialysis (HD) patients. However, it has not been established whether
      elevated plasma IL-6 also predicts outcome in ESRD patients treated by peritoneal
      dialysis (PD), and how it relates to the data on HD patients. The predictive
      power of sIL-6R levels on outcome is also unknown in this patient population.
      METHODS: To determine whether or not plasma IL-6 and sIL-6R predict patient
      survival, we studied 173 ESRD patients (62% males, 53+/-1 years of age) near the
      initiation of dialysis treatment (99 PD, 74 HD patients). The patients were
      followed for a mean period of 3.1+/-0.1 years (range 0.1-7.1 years) and were
      stratified at the start of dialysis treatment according to age, gender, presence
      of cardiovascular disease, malnutrition (determined by subjective global
      assessment), diabetes mellitus, and IL-6 and sIL-6R plasma levels. RESULTS: A
      significantly different (P<0.0001) mortality rate was observed in different
      groups when patients were divided into quartiles according to IL-6 levels.
      Furthermore, the same differences were observed, less notably however, for sIL-6R
      (P<0.05). When patients were stratified according to IL-6 quartiles and analysed
      separately according to the different initial treatment groups, a similar profile
      of survival was observed for PD (P<0.01) and HD (P<0.05) patients. In a Cox
      proportional hazard model adjusting for the impact of age, malnutrition, diabetes
      mellitus and male gender, log IL-6 values were independently associated with poor
      outcome (P<0.05). CONCLUSIONS: The present study demonstrates that the strong
      predictive value of elevated IL-6 levels for poor outcome in ESRD patients is
      similar in both HD and PD patients starting treatment.

PMID- 12198226
TI  - Multifocal transitional cell carcinoma associated with renal cell carcinoma in a
      patient on long-term haemodialysis.

PMID- 12198227
TI  - Recurrence of familial interstitial nephritis following renal transplantation.

PMID- 12198228
TI  - A woman with increasing weakness of the legs and irregular heartbeat who took her
      husband's medication.

PMID- 12198229
TI  - Post-partum 'acute renal failure'.

PMID- 12198230
TI  - Liquid test and sudden death in dialysis patients.

PMID- 12198231
TI  - Persistent macroscopic haematuria in thin membrane nephropathy.

PMID- 12198232
TI  - Determination of parathyroid hormone levels in fine needle aspirates of ectopic
      parathyroid glands.

PMID- 12198233
TI  - Late referral of patients with chronic renal insufficiency: do we nephrologists
      need to change our strategy?

PMID- 12198234
TI  - Does peritoneal dialysis predispose a diabetic patient to icodextrin-induced
      peritonitis?

PMID- 12198236
TI  - Glucocorticoid receptors in hippocampal neurons that do not engage proteasomes
      escape from hormone-dependent down-regulation but maintain transactivation
      activity.
AB  - The glucocorticoid receptor (GR) protein is subjected to hormone-dependent down
      regulation in most cells and tissues. This reduction in receptor levels that
      accompanies chronic hormone exposure serves to limit hormone responsiveness and
      operates at transcriptional, posttranscriptional, and posttranslational levels.
      The ability of glucocorticoid hormones to trigger GR down-regulation may be not
      universal, particularly in mature and developing neurons in which conflicting
      results regarding hormone control of GR protein have been reported. We find that
      endogenous GR is not down-regulated in the HT22 mouse hippocampal cell line and
      in primary hippocampal neurons derived from embryonic rats. Because GR has the
      capacity to be ubiquitylated in HT22 cells, receptor down-regulation must be
      limited by defects in either targeting of polyubiquitylated receptor to the
      proteasome or processing of the targeted receptor by the proteasome. Despite the
      lack of GR down-regulation in the HT22 cells, glucocorticoid-induced
      transcription from transiently transfected templates is attenuated upon prolonged
      hormone treatment. This termination of GR transactivation is not due to
      inefficient nuclear import or nuclear retention of the receptor. Furthermore, GR
      efficiently exports from HT22 cell nuclei in hormone-withdrawn cells, indicating
      that the receptor has access to both nuclear and cytoplasmic degradation
      pathways. Our results suggest that appropriate maturation of proteasomal
      degradative or targeting activities may be required, particularly in hippocampal
      neurons, for hormone-dependent down-regulation of GR.

PMID- 12198238
TI  - Ubc6p and ubc7p are required for normal and substrate-induced endoplasmic
      reticulum-associated degradation of the human selenoprotein type 2 iodothyronine
      monodeiodinase.
AB  - The type 2 monodeiodinase (D2) is an endoplasmic reticulum-resident membrane
      selenoprotein responsible for catalyzing the first step in thyroid hormone
      action, T(4) deiodination to T(3). Its short half-life is due to ubiquitination
      and proteolysis by proteasomes, a mechanism that is accelerated by D2 interaction
      with T(4). To identify proteins involved in D2 ubiquitination, a FLAG-tagged
      selenocystine133-to-Cys mutation of the human D2 (CysD2) was created and
      expressed in Saccharomyces cerevisiae using the GAL1 gene promoter. CysD2
      activity was detected in the microsomes, indistinguishable from transiently
      expressed CysD2 in vertebrate cells. Treatment with 100 mg/ml cycloheximide or 30
      micro M T(4) caused rapid loss of CysD2 (t(1/2) = approximately 30 min). Clasto
      lactacystin beta-lactone not only increased galactose-inducible CysD2 but also
      stabilized CysD2 in the presence of cycloheximide or T(4). Immunoprecipitation
      with anti-FLAG antibody combined with Western analysis with antiubiquitin
      revealed that CysD2 is heavily ubiquitinated. Expression of CysD2 in yeast
      strains that lack the ubiquitin conjugases Ubc6p or Ubc7p stabilized CysD2 half
      life by markedly reducing CysD2 ubiquitination, whereas no difference was
      detected in Ubc1p-deficient mutants. Similarly, expression of CysD2 in UBC6 and
      UBC7 mutants also impaired the substrate-induced loss of CysD2 activity and
      protein. In conclusion, Ubc6p and Ubc7p are required for normal and substrate
      induced ubiquitination and proteolysis of D2.

PMID- 12198239
TI  - The mineralocorticoid receptor may compensate for the loss of the glucocorticoid
      receptor at specific stages of mammary gland development.
AB  - To study the role of glucocorticoid receptor (GR) at different stages of mammary
      gland development, mammary anlage were rescued from GR-/- mice by transplantation
      into the cleared fat pad of wild-type mice. In virgin mice, GR-/- outgrowths
      displayed abnormal ductal morphogenesis characterized by distended lumena,
      multiple layers of luminal epithelial cells in some regions along the ducts, and
      increased periductal stroma. In contrast, the loss of GR did not result in overt
      phenotypic changes in mammary gland development during pregnancy, lactation, and
      involution. Surprisingly, despite the known synergism between glucocorticoids and
      prolactin in the regulation of milk protein gene expression, whey acidic protein
      and beta-casein mRNA levels were unaffected in GR-/- transplants as compared with
      wild-type transplants. That mineralocorticoid receptor (MR) might compensate for
      the loss of GR was suggested by the detection of MR in the mammary gland at d 1
      of lactation. This hypothesis was tested using explant cultures derived from the
      GR-/- transplants in which the mineralocorticoid fludrocortisone was able to
      synergistically induce beta-casein gene expression in the presence of prolactin
      and insulin. These studies suggest that MR may compensate for the absence of GR
      at some, but not at all stages of mammary gland development.

PMID- 12198240
TI  - CPAP is a novel stat5-interacting cofactor that augments stat5-mediated
      transcriptional activity.
AB  - Stat5, a member of the signal transducer and activators of transcription (Stat)
      protein family, is a primary mediator of prolactin (PRL) signaling in the mammary
      gland. There are two distinct Stat5 genes, Stat5a and Stat5b. The Stat5a isoform
      has been demonstrated to have an essential role in mammary epithelial
      differentiation, whereas Stat5b is required for dimorphic sexual growth. To
      search for proteins that interact with the C terminus of Stat5a, a highly
      divergent region amongst Stat family members, we performed a yeast two-hybrid
      screen of HBL100 and primary breast adenocarcinoma libraries. This led to the
      identification of a protein that had previously been isolated as a centrosomal
      P4.1-associated protein (CPAP). CPAP was shown to specifically interact with
      Stat5a and Stat5b but not with Stat1 or Stat3. Both the tyrosine phosphorylated
      and unphosphorylated forms of Stat5, as well as Stat5a/Stat5b heterodimers, could
      associate with CPAP. CPAP was expressed in human breast cancer cell lines and the
      developing mammary gland as well as in other tissues. Indirect immunofluorescence
      and cellular fractionation studies revealed that CPAP was predominantly
      cytoplasmic, with low levels in the nucleus. Nuclear levels of CPAP increased
      substantially upon activation of the PRL pathway, most likely reflecting
      cotranslocation of this protein with activated Stat5. Furthermore, CPAP was found
      to augment Stat5-mediated transcription. Thus, we have identified CPAP as a novel
      coactivator of Stat5 proteins in the PRL (and probably other) pathways.

PMID- 12198241
TI  - Persistent parity-induced changes in growth factors, TGF-beta3, and
      differentiation in the rodent mammary gland.
AB  - Epidemiological studies have repeatedly demonstrated that women who undergo an
      early first full-term pregnancy have a significantly reduced lifetime risk of
      breast cancer. Similarly, rodents that have previously undergone a full-term
      pregnancy are highly resistant to carcinogen-induced breast cancer compared with
      age-matched nulliparous controls. Little progress has been made, however, toward
      understanding the biological basis of this phenomenon. We have used DNA
      microarrays to identify a panel of 38 differentially expressed genes that
      reproducibly distinguishes, in a blinded manner, between the nulliparous and
      parous states of the mammary gland in multiple strains of mice and rats. We find
      that parity results in the persistent down-regulation of multiple genes encoding
      growth factors, such as amphiregulin, pleiotrophin, and IGF-1, as well as the
      persistent up-regulation of the growth-inhibitory molecule, TGF-beta3, and
      several of its transcriptional targets. Our studies further indicate that parity
      results in a persistent increase in the differentiated state of the mammary gland
      as well as lifelong changes in the hematopoietic cell types resident within the
      gland. These findings define a developmental state of the mammary gland that is
      refractory to carcinogenesis and suggest novel hypotheses for the mechanisms by
      which parity may modulate breast cancer risk.

PMID- 12198242
TI  - Evidence for a regulatory role of inducible cAMP early repressor in protein
      kinase a-mediated enhancement of vitamin D receptor expression and modulation of
      hormone action.
AB  - Parathyroid hormone (PTH) or activators of protein kinase A (PKA) up-regulate the
      vitamin D receptor (VDR) and augment the induction by 1,25-dihydroxyvitamin D(3)
      of the expression of target genes (24-hydroxylase and osteopontin) in
      osteoblastic cells. To understand regulatory mechanisms involved, we asked
      whether the inducible cAMP early repressor (ICER), which serves as a dominant
      negative regulator of cAMP-induced transcription in other endocrine systems, may
      similarly play a role in modulation of vitamin D hormone action. In this study we
      demonstrate that PTH or 8-bromo-cAMP rapidly induces ICER mRNA and protein in
      osteoblastic cells. In UMR 106 osteoblastic cells transfected with an expression
      vector containing the ICER II-gamma coding sequence, cAMP or PTH enhancement of
      1,25-dihydroxyvitamin D(3)-induced osteopontin and 24-hydroxylase mRNA and
      transcription is inhibited. The vitamin D response element is sufficient for the
      PKA enhancement of VDR-mediated transcription and is also sufficient to observe
      the inhibitory effect of ICER. Our data indicate that the mechanism of the
      inhibitory effect of ICER involves an inhibition of PKA-induced VDR
      transcription, and this inhibition may be mediated in part by binding of ICER to
      a cAMP response element-like sequence in the VDR promoter. This study provides
      evidence for the first time that ICER has a key regulatory role in the PKA
      enhancement of VDR transcription and therefore in the cross-talk between the PKA
      signaling pathway and the vitamin D endocrine system.

PMID- 12198243
TI  - The small heterodimer partner interacts with the liver X receptor alpha and
      represses its transcriptional activity.
AB  - The small heterodimer partner SHP (NR0B2) is an unusual nuclear receptor that
      lacks the typical DNA binding domain common to most nuclear receptors. SHP has
      been reported to act as a corepressor for several nuclear receptors, but its
      exact mechanism of action is still elusive. Here we show that SHP can interact
      with the liver X receptors LXRalpha (NR1H3) and LXRbeta (NR1H2), as demonstrated
      by glutathione-S-transferase pull-down assays, mammalian two-hybrid, and
      coimmunoprecipitation experiments. In transfection assays, SHP inhibits the
      expression of an artificial reporter driven by an LXR-response element and
      represses the transcriptional activation by LXR of the human ATP-binding cassette
      transporter 1 (ABCA1) promoter. Treatment of Caco-2 cells with bile acids, which
      activate farnesoid X receptor and subsequently induce SHP, leads to the
      repression of the human ABCG1 gene, an established LXR target gene. These results
      demonstrate that SHP is able to interact with LXR and to modulate its
      transcriptional activity.

PMID- 12198244
TI  - Differential expression of thyroid hormone receptor isoforms dictates the
      dominant negative activity of mutant Beta receptor.
AB  - Mutations in the thyroid hormone receptor beta gene (TRbeta) cause resistance to
      thyroid hormone (RTH). Genetic analyses indicate that phenotypic manifestation of
      RTH is due to the dominant negative action of mutant TRbeta. However, the
      molecular mechanisms underlying the dominant negative action of mutants and how
      the same mutation results in marked variability of resistance in different
      tissues in vivo are not clear. Here we used a knock-in mouse (TRbetaPV mouse)
      that faithfully reproduces human RTH to address these questions. We demonstrated
      directly that TRbeta1 protein was approximately 3-fold higher than TRalpha1 in
      the liver of TRbeta(+/+) mice but was not detectable in the heart of wild-type
      and TRbetaPV mice. The abundance of PV in the liver of TRbeta(PV/PV) was more
      than TRbeta(PV/+) mice but not detectable in the heart. TRalpha1 in the liver was
      approximately 6-fold higher than that in the heart of wild-type and TRbetaPV
      mice. Using TR isoforms and PV-specific antibodies in gel shift assays, we found
      that in vivo, PV competed not only with TR isoforms for binding to thyroid
      hormone response elements (TRE) but also competed with TR for the retinoid X
      receptors in binding to TRE. These competitions led to the inhibition of the
      thyroid hormone (T(3))-positive regulated genes in the liver. In the heart,
      however, PV was significantly lower and thus could not effectively compete with
      TRalpha1 for binding to TRE, resulting in activation of the T(3)-target genes by
      higher levels of circulating thyroid hormones. These results indicate that in
      vivo, differential expression of TR isoforms in tissues dictates the dominant
      negative activity of mutant beta receptor, thereby resulting in variable
      phenotypic expression in RTH.

PMID- 12198245
TI  - Episodic activation of the rat GnRH promoter: role of the homeoprotein oct-1.
AB  - Recent reports demonstrate that the rat GnRH promoter is activated in an episodic
      fashion in immortalized GnRH neurons, but little information is available on
      molecular processes that contribute to this phenomenon. In this study, we
      dissected the regions of the rat GnRH promoter that mediate these effects by
      testing a series of 5' deletion luciferase reporter constructs on the pattern of
      photonic emissions from single, living GT1-7 GnRH neuronal cells. Deletion
      analysis revealed that the region -2012/-1597 that contains the neuron-specific
      enhancer (NSE) was required for the elaboration of pulses of GnRH promoter
      activity. The importance of this region was supported by observations that
      episodic reporter activity could be transferred to a neutral nonpulsatile
      promoter (Rous sarcoma virus, RSV(180)). Immunoneutralization of Oct-1 as well as
      mutation of an octamer binding site located at -1787/-1783 (AT-a site) blocked
      the pulsatile GnRH promoter activity in GT1-7 neuronal cells. Taken together, our
      findings indicate that episodic GnRH gene expression is a promoter-dependent
      phenomenon, which is mediated by Oct-1 interaction with regulatory elements in
      the NSE region.

PMID- 12198246
TI  - Identification of the RUSH consensus-binding site by cyclic amplification and
      selection of targets: demonstration that RUSH mediates the ability of prolactin
      to augment progesterone-dependent gene expression.
AB  - RUSH-1alpha(beta) transcription factors were cloned by recognition site screening
      with an 85-bp region (-170/-85) of the rabbit uteroglobin gene. Deletion analysis
      showed this region was essential to prolactin (PRL) action, but conclusions were
      limited by the complexity of the large deletion. Cyclic amplification and
      selection of targets (CASTing) was used to identify the RUSH-binding site (-126/
      121). Endometrial nuclear proteins were incubated with a pool of degenerate
      oligonucleotides and immunoprecipitated with RUSH-1alpha(beta) antibodies. Bound
      DNA was amplified by PCR. The consensus motif (MCWTDK) was identified after five
      rounds of CASTing, authenticated by CASTing with RUSH-1alpha-specific antibodies
      and recombinant protein, and refined with EMSA. Dissociation rate constants (K(d)
      = 0.1-1.0 nM; r = 0.99) revealed high-affinity binding. Chromatin
      immunoprecipitation confirmed in vivo binding of RUSH to the transcriptionally
      active uteroglobin promoter. CASTing also revealed RUSH-GATA transcription factor
      interactions. Endometrial GATA-4 expression is progesterone dependent (Northern
      analysis) and preferentially localized in the epithelium (in situ hybridization).
      Although physically affiliated with RUSH, uterine forms of GATA-4 were not
      required for RUSH-DNA binding. Site-directed mutagenesis and transient
      transfection assays showed the RUSH motif mediates the ability of PRL to augment
      progesterone-dependent uteroglobin transcription. RUSH is central to the
      mechanism whereby PRL augments progesterone-dependent gene transcription.

PMID- 12198247
TI  - Angiotensin II subtype 2 receptor activation inhibits insulin-induced
      phosphoinositide 3-kinase and Akt and induces apoptosis in PC12W cells.
AB  - In the present study, we identified novel negative cross-talk between the
      angiotensin II subtype 2 (AT2) receptor and insulin receptor signaling in the
      regulation of phosphoinositide 3-kinase (PI3K), Akt, and apoptosis in rat
      pheochromocytoma cell line, PC12W cells, which exclusively express AT2 receptor.
      We demonstrated that insulin-mediated insulin receptor substrate (IRS)-2
      associated PI3K activity was inhibited by AT2 receptor stimulation, whereas IRS-1
      associated PI3K activity was not significantly influenced. AT2 receptor
      stimulation did not change insulin-induced tyrosine phosphorylation of IRS-2 or
      its association with the p85alpha subunit of PI3K, but led to a significant
      reduction of insulin-induced p85alpha phosphorylation. AT2 receptor stimulation
      increased the association of a protein tyrosine phosphatase, SHP-1, with IRS-2.
      Moreover, we demonstrated that AT2 receptor stimulation inhibited insulin-induced
      Akt phosphorylation and that insulin-mediated antiapoptotic effect was also
      blocked by AT2 receptor activation. Overexpression of a catalytically inactive
      dominant negative SHP-1 markedly attenuated the AT2 receptor- mediated inhibition
      of IRS-2-associated PI3K activity, Akt phosphorylation, and antiapoptotic effect
      induced by insulin. Taken together, these results indicate that AT2 receptor
      mediated activation of SHP-1 and the consequent inhibition IRS-2-associated PI3K
      activity contributed at least partly to the inhibition of Akt phosphorylation,
      thereby inducing apoptosis.

PMID- 12198248
TI  - The effect of suppressor of cytokine signaling 3 on GH signaling in beta-cells.
AB  - GH is an important regulator of cell growth and metabolism. In the pancreas, GH
      stimulates mitogenesis as well as insulin production in beta-cells. The cellular
      effects of GH are exerted mainly through activation of the Janus kinase-signal
      transducer and activator of transcription (STAT) pathway. Recently it has been
      found that suppressors of cytokine signaling (SOCS) proteins are able to inhibit
      GH-induced signal transduction. In the present study, the role of SOCS-3 in GH
      signaling was investigated in the pancreatic beta-cell lines RIN-5AH and INS-1 by
      means of inducible expression systems. Via stable transfection of the beta-cell
      lines with plasmids expressing SOCS-3 under the control of an inducible promoter,
      a time- and dose-dependent expression of SOCS-3 in the cells was obtained. EMSA
      showed that SOCS-3 is able to inhibit GH-induced DNA binding of both STAT3 and
      STAT5 in RIN-5AH cells. Furthermore, using Northern blot analysis it was shown
      that SOCS-3 can completely inhibit GH-induced insulin production in these cells.
      Finally, 5-bromodeoxyuridine incorporation followed by fluorescence-activated
      cell sorting analysis showed that SOCS-3 inhibits GH-induced proliferation of INS
      1 cells. These findings support the hypothesis that SOCS-3 is a major regulator
      of GH signaling in insulin-producing cells.

PMID- 12198250
TI  - Induction of cyclooxygenase-2 gene in pancreatic beta-cells by 12-lipoxygenase
      pathway product 12-hydroxyeicosatetraenoic acid.
AB  - Cyclooxygenase-2 (COX-2) gene and 12-lipoxygenase (12-LO) gene are preferentially
      expressed over other types of cyclooxygenase and lipoxygenase in pancreatic beta
      cells. Inhibition of either COX-2 or 12-LO can prevent cytokine-induced
      pancreatic beta-cell dysfunction as defined by inhibition of glucose-stimulated
      insulin secretion. As cellular stress induces both genes and their respective end
      products in pancreatic beta-cells, we evaluated the role of 12
      hydroxyeicosatetraenoic acid (HETE) on COX-2 gene expression, protein expression,
      and prostaglandin E2 (PGE2) production. We demonstrate that 12-HETE significantly
      increases COX-2 gene expression and consequent product formation, whereas a
      closely related lipid, 15-HETE, does not. In addition, IL-1beta-stimulated
      prostaglandin E2 production is completely inhibited by a preferential
      lipoxygenase inhibitor cinnaminyl-3,4-dihydroxy-alpha-cyanocinnamate. We then
      evaluated IL-1beta-induced PGE2 production in islets purified from control
      C57BL/6 mice and 12-LO knockout mice lacking cytokine-inducible 12-HETE. IL-1beta
      stimulated an 8-fold increase in PGE2 production in C57BL/6 islets but failed to
      stimulate PGE2 in 12-LO knockout islets. Addition of 12-HETE to 12-LO knockout
      islet cells produced a statistically significant rise in PGE2 production.
      Furthermore, 12-HETE, but not 15-HETE, stimulated COX-2 promoter and activator
      protein-1 binding activity. These data demonstrate that 12-HETE mediates cytokine
      induced COX-2 gene transcription and resultant PGE2 production in pancreatic beta
      cells.

PMID- 12198249
TI  - Glucagon-like peptide-1 inhibits pancreatic ATP-sensitive potassium channels via
      a protein kinase A- and ADP-dependent mechanism.
AB  - Glucagon-like peptide-1 (GLP-1) elicits a glucose-dependent insulin secretory
      effect via elevation of cAMP and activation of protein kinase A (PKA). GLP-1
      mediated closure of ATP-sensitive potassium (K(ATP)) channels is involved in this
      process, although the mechanism of action of PKA on the K(ATP) channels is not
      fully understood. K(ATP) channel currents and membrane potentials were measured
      from insulin-secreting INS-1 cells and recombinant beta-cell K(ATP) channels. 20
      nM GLP-1 depolarized INS-1 cells significantly by 6.68 +/- 1.29 mV. GLP-1 reduced
      recombinant K(ATP) channel currents by 54.1 +/- 6.9% in mammalian cells
      coexpressing SUR1, Kir6.2, and GLP-1 receptor clones. In the presence of 0.2 mM
      ATP, the catalytic subunit of PKA (cPKA, 20 nM) had no effect on SUR1/Kir6.2
      activity in inside-out patches. However, the stimulatory effects of 0.2 mM ADP on
      SUR1/Kir6.2 currents were reduced by 26.7 +/- 2.9% (P < 0.05) in the presence of
      cPKA. cPKA increased SUR1/Kir6.2 currents by 201.2 +/- 20.8% (P < 0.05) with 0.5
      mM ADP present. The point mutation S1448A in the ADP-sensing region of SUR1
      removed the modulatory effects of cPKA. Our results indicate that PKA-mediated
      phosphorylation of S1448 in the SUR1 subunit leads to K(ATP) channel closure via
      an ADP-dependent mechanism. The marked alteration of the PKA-mediated effects at
      different ADP levels may provide a cellular mechanism for the glucose-sensitivity
      of GLP-1.

PMID- 12198251
TI  - Conformational constraint of mammalian, chicken, and salmon GnRHs, but not GnRH
      II, enhances binding at mammalian and nonmammalian receptors: evidence for
      preconfiguration of GnRH II.
AB  - Mammalian GnRH (mGnRH) is believed to interact with mGnRH type I receptors in a
      beta-II' turn conformation involving residues 5-8. This conformation can be
      constrained by substitution of a D-amino acid at position 6 or by a lactam ring
      involving residues 6 and 7, thereby increasing receptor binding affinity. It has
      been proposed that this is not the case for non-mGnRH receptors. However, we show
      that this conformational constraint increases the binding affinity of mammalian,
      chicken, and salmon GnRH for the chicken and catfish receptors, as well as for
      the mouse receptor. Therefore, we conclude that the beta-II' turn conformation
      enhances ligand binding for non-mGnRH as well as mGnRH type I receptors. In
      contrast, most substitutions of a D-amino acid in position 6 have limited effect
      on binding affinity for GnRH II. We suggest that this ligand is preconfigured
      through intramolecular interactions, which accounts for its high binding affinity
      and total conservation of primary structure over 500 million years of evolution.

PMID- 12198252
TI  - The cyclin D1 and cyclin A genes are targets of activated PTH/PTHrP receptors in
      Jansen's metaphyseal chondrodysplasia.
AB  - Jansen's metaphyseal chondrodysplasia (JMC) is an autosomal dominant disorder
      characterized by short-limbed dwarfism, delayed ossification, and hypercalcemia.
      Activating mutations in the PTH/PTHrP receptor have been identified as the
      molecular cause of this disorder. Although these mutations have been shown to
      increase cAMP accumulation, little is known about possible target genes of the
      downstream signaling pathways that may contribute to the pathogenesis of the
      disease. Here we demonstrate that JMC mutations of the PTH/PTHrP receptor induce
      activation of the cyclin D1 and cyclin A promoters in primary mouse chondrocytes
      and rat chondrosarcoma cells. Induction of cyclin D1 expression is required for
      stimulation of E2F-dependent transcription by mutant receptors. Activation of the
      cyclin D1 and cyclin A promoters requires a functional cAMP response element in
      both genes. Inhibition of protein kinase A or the transcription factor cAMP
      response element binding protein blocks the stimulation of both promoters by
      mutant receptors, whereas inhibition of activating transcription factor 2, c-Fos,
      or c-Jun has only minor effects. In summary, our data suggest that stimulation of
      cell cycle gene expression and cell cycle progression by mutant PTH/PTHrP
      receptors contribute to the pathogenesis of JMC.

PMID- 12198255
TI  - Blaming tobacco's victims.

PMID- 12198256
TI  - Philip Morris changes its name, but not its harmful practices.
AB  - After spending more than $250 million on an advertising campaign to improve its
      name and reputation, Philip Morris has abruptly shifted course and decided
      instead to change its corporate name-to The Altria Group, Inc.

PMID- 12198257
TI  - Italy: court's expert panel condemns tobacco.

PMID- 12198258
TI  - Hong Kong: Marlboro tries it on (the pack).

PMID- 12198259
TI  - Europe: Rodin's non-thinker.

PMID- 12198260
TI  - South Asia: the party goes on.

PMID- 12198261
TI  - PM: "We agree that our brands cause lung cancer in smokers".

PMID- 12198262
TI  - Togo: mobile frenzy as Bond goes in for the kill.

PMID- 12198263
TI  - Smoke in the machine: industry's nervous puff over Tobacco Control report.

PMID- 12198264
TI  - The Circumlocution Hall of Fame: and the winner is.

PMID- 12198265
TI  - Hair as a biomarker for exposure to tobacco smoke.
AB  - This article provides an overview of the hair nicotine biomarker for assessment
      of exposure to tobacco smoke, with emphasis on environmental tobacco smoke (ETS).
      Measurement of nicotine in hair can be an informative tool for research looking
      at ETS and related illnesses. There are still unresolved issues in relation to
      this biomarker such as influence of hair treatment, hair colour, and growth rate
      on nicotine levels in hair, which need to be addressed in order to further refine
      this biomarker for exposure assessment. Nevertheless, hair nicotine promises to
      be a valid and reliable measure of longer term exposure that can be readily
      applied in epidemiological studies of exposure to tobacco smoke, and more
      specifically ETS, and its risk to health.

PMID- 12198266
TI  - Enhancing the effectiveness of tobacco package warning labels: a social
      psychological perspective.
AB  - OBJECTIVE: To outline social psychological principles that could influence the
      psychosocial and behavioural effects of tobacco warning labels, and to inform the
      development of more effective tobacco warning labels. DATA SOURCES: PsycInfo and
      Medline literature searches and expert guided selection of principles and
      theories in social psychology and of tobacco warning labels, including articles,
      books, and reports. CONCLUSIONS: Tobacco warning labels represent a potentially
      effective method of influencing attitudes and behaviours. This review describes
      social psychological principles that could be used to guide the creation of more
      effective warning labels. The potential value of incorporating warning labels
      into a broader public health education campaign is discussed, and directions for
      future research are suggested.

PMID- 12198267
TI  - Tobacco point of sale advertising increases positive brand user imagery.
AB  - OBJECTIVES: To determine the potential impact of point of sale advertising on
      adolescents so as to inform changes to the Tobacco Control Act. DESIGN:
      Participants were randomly assigned to one of two conditions. In the control
      condition, students were exposed to a photograph of a packet of cigarettes; in
      the intervention condition, students were exposed to an ad for cigarettes,
      typical of point of sale advertising posters. All students then rated the brand
      user on a set of 12 bipolar adjectives. Two brands were used in the study: Benson
      & Hedges, and Marlboro. SUBJECTS: One hundred year (grade) 6 and 7 students (age
      range 10-12 years), from four Western Australian metropolitan primary schools,
      participated in the study. RESULTS: In a majority of the brand user descriptions,
      the cigarette advertisements increased brand user imagery in a positive way,
      especially for Benson & Hedges. For example, participants viewing the Benson &
      Hedges advertisement, as distinct from those viewing the Benson & Hedges pack
      only, were more likely to describe the Benson & Hedges user as relaxed,
      interesting, cool, rich, adventurous, and classy. Relative to the Marlboro pack
      only, the Marlboro ad increased positive perceptions of the Marlboro user on
      adventurous, interesting, and relaxed. CONCLUSIONS: The results presented here
      support restrictions being placed on advertising at point of sale, since such ads
      have the potential to increase positive brand user imagery directly in the
      situation where a product purchase can take place, and hence the potential to
      increase the likelihood of impulse purchasing.

PMID- 12198268
TI  - Public opinion on smoke-free policies in restaurants and predicted effect on
      patronage in Hong Kong.
AB  - BACKGROUND: The Hong Kong government has proposed legislation for smoke-free
      policies in all restaurants and bars. This is opposed by certain sections of the
      catering industry. OBJECTIVE: To assess public opinion on smoke-free restaurants
      and to estimate changes in patronage. DESIGN: A population based, cross sectional
      random digit dialling telephone survey conducted from November 1999 to January
      2000. SETTING AND PARTICIPANTS: 1077 randomly selected subjects age 15 years or
      over (response fraction of 81.6%). RESULTS: 68.9% (95% confidence interval (CI)
      66.2% to 71.7%) supported a totally smoke-free policy in restaurants. Experiences
      of discomfort or symptoms from second hand smoke in restaurants were common. The
      majority (77.2%, 95% CI 74.7% to 79.7%) anticipated no change in their frequency
      of use of restaurants after a smoke-free policy. Increased use was predicted by
      19.7% (95% CI 17.3% to 22.1%) of respondents, whereas 3.2% (95% CI 2.2% to 4.4%)
      stated that they would dine out less often. In multivariate analyses, non-smokers
      (adjusted odds ratio (OR) 4.9), people who ate three times or less per week in
      restaurants as compared to those who ate >10 times per week (OR 2.1), those who
      had previous experience of discomfort from exposure to passive smoking in
      restaurants (OR 2.8), or who had avoided restaurants in the past because of
      smoking (OR 1.9), were more likely to support a totally smoke-free policy in
      restaurants. Smoke-free policies do not appear to have an adverse effect on
      restaurants, and may increase business by a considerable margin. CONCLUSION: This
      comprehensive survey-the first in Asia-shows strong community support for smoke
      free dining and predicts an overall increase in the patronage of restaurants
      after the introduction of legislation for totally smoke-free restaurants.

PMID- 12198269
TI  - Targeting of Asian Americans and Pacific Islanders by the tobacco industry:
      results from the Minnesota Tobacco Document Depository.
AB  - OBJECTIVE: The study objective was to review internal tobacco industry documents
      written between 1985 and 1995 regarding the Asian American and Pacific Islander
      (AAPI) population in the USA. These documents detail opportunities and barriers
      to promotion of tobacco products, as viewed by the tobacco industry and its
      market research firms. DATA SOURCES: /methods: Researchers reviewed tobacco
      industry documents from the document depository in Minneapolis, Minnesota and the
      tobacco industry's website, The Tobacco Archive, in a systematic fashion. A
      combined technique was employed using title keywords, dates, and names to search
      the 4(b) index. FINDINGS: A review of internal tobacco company documents reveal
      that during the late 1980s, the industry and its market research firms recognised
      the importance of the AAPI community as a potential business market. Documents
      describe the population growth in this community, the high prevalence of smoking
      in countries of origin, high purchasing power of AAPI immigrants, cultural
      predisposition to smoking, opportunities afforded by the high proportion of
      retail businesses under AAPI ownership, barriers to developing the AAPI market,
      comprehensive campaigns, and political and lobbying efforts. Comprehensive
      campaigns were designed to integrate promotion efforts in AAPI consumer, retail,
      and business communities. CONCLUSIONS: The documents show that the tobacco
      industry developed specific promotion strategies to target the AAPI population.
      Tobacco control initiatives in the AAPI group have been slower to develop than in
      other targeted ethnic groups, and may benefit by increased awareness of industry
      methods to promote tobacco use.

PMID- 12198270
TI  - Tobacco smoking in Tanzania, East Africa: population based smoking prevalence
      using expired alveolar carbon monoxide as a validation tool.
AB  - OBJECTIVES: To describe the prevalence of tobacco smoking in an urban East
      African population while using a simple validation procedure to examine the
      degree of under reporting in men and women. DESIGN: A cross sectional population
      based study in adults (15 years and over) with sampling from a well maintained
      census register. SETTING: Ilala Ilala, a middle income district of Dar es Salaam,
      Tanzania. SUBJECTS: An age and sex stratified random sample of 973 men and women.
      MAIN OUTCOME MEASURES: Self reported smoking status with correction by exhaled
      alveolar carbon monoxide (EACO). RESULTS: From the 605 participants (response
      rate 67.9%) age standardised (new world population) smoking prevalence, based on
      questionnaire and EACO, was 27.0% (95% confidence interval (CI) 20.8% to 33.2%)
      in males and 5.0% (95% CI 2.8% to 7.2%) in females. The age specific prevalence
      of smoking was highest in the age group 35-54 years (34.3%) for men and in the
      over 54 years group (16%) for women. Of those classified as smokers, 7.3% of men
      and 27.3% of women were reclassified as current smokers based on EACO (> or = 9
      parts per million), after they had reported themselves to be an ex- or non-smoker
      in the questionnaire. CONCLUSIONS: The data suggest: (1) high rates of smoking
      among men in an urban area of East Africa; and (2) the importance of validating
      self reports of smoking status, particularly among women.

PMID- 12198271
TI  - Case studies in international tobacco surveillance: cigarette smuggling in
      Brazil.
AB  - OBJECTIVE: This article is the first in a series of international case studies
      developed by the American Cancer Society to illustrate use of publicly available
      surveillance data for regional tobacco control. DESIGN: A descriptive analysis of
      Brazil and Paraguay cigarette production and trade data from official sources.
      METHODS: Per capita cigarette consumption for Brazil and its neighbour was
      calculated from 1970 to 1998 using data on production, imports, and exports from
      NATIONS, the National Tobacco Information Online System. RESULTS: A 63% decrease
      was observed in the estimate of per capita consumption of cigarettes in Brazil
      between 1986 and 1998 (from 1913 cigarettes per person in 1986 to 714 cigarettes
      per person in 1998) and a 16-fold increase in Paraguay was observed during the
      same period (from 678 cigarettes per person in 1986 to 10 929 cigarettes per
      person in 1998). Following Brazil's 1999 passage of a 150% cigarette export tax,
      cigarette exports fell 89% and Brazil's estimated per capita consumption rose to
      1990 levels (based on preliminary data). Per capita consumption in Paraguay also
      fell to 1990 levels. CONCLUSIONS: These trends coincide with local evidence that
      large volumes of cigarettes manufactured in Brazil for export to Paraguay are
      smuggled back and consumed as tax-free contraband in Brazil. It is hoped that
      this case study will draw wider public attention to the problems that smuggling
      presents for tobacco control, help identify other countries confronting similar
      issues, and stimulate effective interventions.

PMID- 12198272
TI  - Association between exposure to environmental tobacco smoke and the development
      of acute coronary syndromes: the CARDIO2000 case-control study.
AB  - OBJECTIVE: To investigate the association between environmental tobacco smoke
      (ETS) exposure (at least 30 minutes a day) and the risk of developing acute
      coronary syndromes (ACS). DESIGN AND SETTING: The CARDIO2000 is a case-control
      study which was conducted in Greece from 2000 to 2001. Cases included 847
      individuals with a first event of ACS and 1078 cardiovascular disease-free
      controls. Cases and controls were frequency matched on age (within three years of
      age), sex, and region. MAIN OUTCOME MEASURES: ACS was defined as a diagnosis of
      first acute myocardial infarction or unstable angina. Main independent variable:
      Exposure to ETS was measured by self report as follows: after the second day of
      hospitalisation for the cases, and at the entry for the controls, participants
      were asked whether they were currently exposed to tobacco smoke from other people
      (home and/or work) for more than 30 minutes a day. The responses were categorised
      into three levels: no exposure, occasional exposure (< 3 times per week), and
      regular exposure. In addition participants were asked how many years they had
      been exposed. Because these were self reported assessments and prone to bias, the
      results were compared to reports obtained from subjects' relatives or friends,
      using the Kendal's tau coefficient that showed high agreement. RESULTS: 731 (86%)
      of the patients and 605 (56%) of the controls reported current exposure of 30
      minutes per day or more to ETS. Among current non-smokers, cases were 47% more
      likely to report regular exposure to ETS (odds ratio (OR) 1.47, 95% confidence
      interval (CI) 1.26 to 1.80) compared to controls. Exposure to ETS at work was
      associated with a greater risk of ACS compared to home exposure (+97% v +33%).
      The risk of ACS was also raised in active smokers (OR 2.83, 95% CI 2.07 to 3.31)
      regularly exposed to ETS. CONCLUSIONS: This study supports the hypothesis that
      exposure to ETS increases the risk of developing ACS. The consistency of these
      findings with the existing totality of evidence presented in the literature
      supports the role of ETS in the aetiology of ACS.

PMID- 12198273
TI  - Online sales: profit without question.
AB  - OBJECTIVES: To examine the ease with which underage smokers can purchase
      cigarettes online using money orders and to evaluate the effectiveness of
      internet filtering programs in blocking access to internet cigarette vendors
      (ICVs). DESIGN: Four young people purchased 32 money orders using 32 different
      names to buy one carton of cigarettes for each named individual. Each money order
      was subsequently mailed to a different ICV in the USA. No age related information
      accompanied these online orders. Two internet filtering programs ("Bess" and
      filtertobacco.org) were tested for their relative efficacy in blocking access to
      ICV sites. RESULTS: Of the 32 orders placed, four orders never reached the
      intended ICV. Of the remaining 28 orders, 20 (71%) were filled despite a lack of
      age verification. Only four (14%) of the orders received were rejected because
      they lacked proof of age. "Bess" blocked access to 84% and filtertobacco.org to
      94% of the ICV sites. CONCLUSIONS: Although underage smokers can easily purchase
      cigarettes online using money orders, access to these sites can be largely
      blocked if appropriate filtering devices are installed.

PMID- 12198275
TI  - Young adults' opinions of Philip Morris and its television advertising.
AB  - OBJECTIVE: To determine what young people think about the tobacco company Philip
      Morris and how it affects their evaluations of the company's new television
      advertising. DESIGN: Data were gathered in the context of a controlled experiment
      in which participants saw four Philip Morris ads about youth smoking prevention,
      four Philip Morris ads about charitable works, or four Anheuser-Busch ads about
      preventing underage drinking (the control group). Knowledge and opinion of Philip
      Morris were measured before ad exposure. SETTING: A California state university
      in the San Francisco Bay area. SUBJECTS: A convenience sample of undergraduates
      (n = 218) aged 18-25 years. MAIN OUTCOME MEASURES: Advertising evaluation
      measured by 12 semantic differential scales. RESULTS: A little more than half of
      the students knew that Philip Morris is a tobacco company. Neither this knowledge
      nor students' smoking status was related to their opinion of the company. Philip
      Morris ads were rated less favourably by students who were aware that the sponsor
      is a tobacco company than by students who were unaware. CONCLUSIONS:
      Advertisements designed to discredit the tobacco industry typically avoid
      references to specific companies. This study suggests that such counter
      advertising would benefit from teaching audiences about the industry's corporate
      identities.

PMID- 12198276
TI  - Is smoking a communicable disease? Effect of exposure to ever smokers in school
      tutor groups on the risk of incident smoking in the first year of secondary
      school.
AB  - OBJECTIVE: To estimate the effect of joining a first year secondary school tutor
      group with a high prevalence of ever smoking on the risk of incident smoking in
      schoolchildren. DESIGN: Cross-sectional questionnaire survey. SETTING: 10
      randomly selected secondary schools in Nottinghamshire, UK. PARTICIPANTS: Pupils
      in years (grades) 7-11 (aged 11-16 years). MAIN OUTCOME MEASURE: Incident smoking
      in the first year of secondary education, defined as pupils who reported smoking
      their first cigarette during year 7. RESULTS: Of 6522 pupils (75% of those
      eligible) who completed the questionnaire, 17% were current smokers and 49% had
      ever smoked, of whom 23% had started smoking in year 7. Incident smoking in year
      7 was more common in girls, in children with parents or siblings who smoke, and
      in more deprived children, and was independently increased in relation to the
      proportion of ever smokers in the year 7 tutor group joined by the child
      (adjusted odds ratio of incident smoking for a child joining a year 7 tutor group
      in the highest relative to the lowest quartile of ever smoking prevalence 1.45,
      95% confidence interval (CI) 1.11 to 1.89). Exposure to ever smokers in year 7
      tutor groups also accounted for most of the increased risk of incident smoking
      associated with socioeconomic deprivation. CONCLUSIONS: The risk of incident
      smoking in children entering secondary education is independently increased by
      exposure to other ever smokers in school tutor groups. Incident smoking in
      adolescents is thus to some extent a communicable disorder, and may be partly
      preventable by policies that reduce exposure to smoking at school.

PMID- 12198274
TI  - Development of symptoms of tobacco dependence in youths: 30 month follow up data
      from the DANDY study.
AB  - OBJECTIVE: To determine if there is a minimum duration, frequency or quantity of
      tobacco use required to develop symptoms of dependence. DESIGN AND SETTING: A
      retrospective/prospective longitudinal study of the natural history of tobacco
      dependence employing individual interviews conducted three times annually in two
      urban school systems over 30 months. Detailed histories of tobacco use were
      obtained including dates, duration, frequency, quantity, patterns of use, types
      of tobacco, and symptoms of dependence. PARTICIPANTS: A cohort of 679 seventh
      grade students (age 12-13 years). MAIN OUTCOME MEASURES: The report of any of 11
      symptoms of dependence. RESULTS: Among 332 subjects who had used tobacco, 40%
      reported symptoms, with a median latency from the onset of monthly smoking of 21
      days for girls and 183 days for boys. The median frequency of use at the onset of
      symptoms was two cigarettes, one day per week. The report of one or more symptoms
      predicted continued smoking through the end of follow up (odds ratio (OR) 44, 95%
      confidence interval (CI) 17 to 114, p < 0.001). CONCLUSIONS: Symptoms of tobacco
      dependence commonly develop rapidly after the onset of intermittent smoking,
      although individuals differ widely in this regard. Girls tend to develop symptoms
      faster. There does not appear to be a minimum nicotine dose or duration of use as
      a prerequisite for symptoms to appear. The development of a single symptom
      strongly predicted continued use, supporting the theory that the loss of autonomy
      over tobacco use begins with the first symptom of dependence.

PMID- 12198278
TI  - Exposure to teachers smoking and adolescent smoking behaviour: analysis of cross
      sectional data from Denmark.
AB  - OBJECTIVE: To determine whether adolescent smoking behaviour is associated with
      their perceived exposure to teachers or other pupils smoking at school, after
      adjustment for exposure to smoking at home, in school, and best friends smoking.
      DESIGN: Logistic regression analysis of cross sectional data from students in
      Denmark. SUBJECTS: 1515 grade 9 students (mean age 15.8) from 90 classes in 48
      Danish schools. OUTCOME MEASURE: Self reported smoking behaviour; daily smoking
      and heavy smoking, defined as those smoking more than 20 cigarettes per week.
      RESULTS: Of the students in this study, 62% of boys and 60% of girls reported
      being exposed to teachers smoking outdoors on the school premises. The proportion
      of boys and girls reporting to have been exposed to teachers smoking inside the
      school building were 86% and 88%, respectively. Furthermore, 91% of boys and 92%
      of girls reported that they had seen other students smoking outdoors on the
      school premises. Adolescents' perceived exposure to teachers smoking outdoors on
      the school premises was significantly associated with daily smoking, having
      adjusted for sex, exposure to teachers smoking indoors at school and pupils
      smoking outdoors at school, as well as the smoking behaviour of mother, father,
      and best friend (odds ratio (OR) 1.8, 95% confidence interval 1.2 to 2.8).
      Adolescents' perceived exposure to teachers smoking inside the school building
      was not associated with daily smoking (OR 0.9, 95% CI 0.5 to 1.6) and perceived
      exposure to pupils smoking outdoors was not associated with daily smoking
      (adjusted OR 1.5, 95% CI 0.5 to 4.4). There were similar findings with heavy
      smoking as the outcome variable. CONCLUSIONS: Teachers smoking during school
      hours is associated with adolescent smoking. This finding has implications for
      future tobacco prevention strategies in schools in many countries with liberal
      smoking policies where it might provide support for those working to establish
      smokefree schools.

PMID- 12198280
TI  - Tobacco use among youth: a cross country comparison.
AB  - OBJECTIVE: The Global Youth Tobacco Survey (GYTS) is a worldwide collaborative
      surveillance initiative that includes governments and non-governmental
      organisations under the leadership of the World Health Organization/Tobacco Free
      Initiative (WHO/TFI) and the US Centers for Disease Control and Prevention/Office
      on Smoking and Health (CDC/OSH). The GYTS was developed to enhance the capacity
      of countries to design, implement, and evaluate tobacco control and prevention
      programmes. METHODS: The GYTS employs a standard methodology where self
      administered questionnaires, consisting of a set of core questions, are completed
      by a representative school based sample of students primarily between the ages of
      13-15 years. RESULTS: Data are presented from 75 sites in 43 countries and the
      Gaza Strip/West Bank region. Current use of any tobacco product ranges from 62.8%
      to 3.3%, with high rates of oral tobacco use in certain regions. Current
      cigarette smoking ranges from 39.6% to less than 1%, with nearly 25% of students
      who smoke, having smoked their first cigarette before the age of 10 years. The
      majority of current smokers want to stop smoking and have already tried to quit,
      although very few students who currently smoke have ever attended a cessation
      programme. Exposure to advertising is high (75% of students had seen pro-tobacco
      ads), and exposure to environmental tobacco smoke (ETS) is very high in all
      countries. Only about half of the students reported that they had been taught in
      school about the dangers of smoking during the year preceding the survey.
      CONCLUSIONS: Global youth tobacco use is already widespread throughout the world,
      but there is great variation among nations. Valid and reliable data on the extent
      of youth tobacco use, and correlates of use, are essential to plan and evaluate
      tobacco use prevention programmes. The GYTS has proven the feasibility of an
      inexpensive, standardised, worldwide surveillance system for youth tobacco use.
      The GYTS will be expanded to the majority of countries in the next few years, and
      can serve as a baseline for monitoring and evaluating global and national tobacco
      control efforts.

PMID- 12198283
TI  - BAT flouts tobacco-free World Cup policy.
AB  - In Malaysia, British American Tobacco flouted the World Cup of football's no
      tobacco ruling

PMID- 12198281
TI  - The shredding of BAT's defence: McCabe v British American Tobacco Australia.
AB  - On 11 April 2002, a Victorian supreme court jury ordered British American Tobacco
      Australia to pay Rolah McCabe $A700 000 in damages. Rolah McCabe is a 51 year old
      woman dying of lung cancer. She is the first smoker ever in Australia to obtain a
      damages verdict against the tobacco industry

PMID- 12198285
TI  - Events of 11 September 2001 significantly reduced calls to the New Zealand
      Quitline.

PMID- 12198286
TI  - Big Mac index of cigarette affordability.

PMID- 12198287
TI  - Studying the Hungarian anti-smoking movement.

PMID- 12198288
TI  - Is it time to abandon youth access programmes?

PMID- 12198289
TI  - Health messages on smoking and breastfeeding in maternity hospitals of Eastern
      Europe.

PMID- 12198290
TI  - Filter vent blocking.

PMID- 12198291
TI  - Tobacco industry documents: comparing the Minnesota Depository and internet
      access.

PMID- 12198293
TI  - Flat bulk-solvent model: obtaining optimal parameters.
AB  - A bulk-solvent correction is regularly used for macromolecular refinement. The
      flat model of the bulk solvent is considered to be the most reliable. It is shown
      that the standard procedure does not always result in the optimal values of the
      bulk-solvent correction parameters. A method to obtain the best values for
      parameters k(sol) and B(sol) of the flat-solvent model is discussed. The values
      of correctly determined parameters for crystallographic structures deposited in
      the Protein Data Bank are clustered around k(sol) = 0.35 e A(-3) and B(sol) = 46
      A(2), which have a reasonable physical meaning. Such a distribution allows the
      use of these mean values of solvent parameters for many practical applications
      when refined parameters cannot be obtained, especially when an atomic model in
      the unit cell is not yet known.

PMID- 12198294
TI  - Analysis of quinazoline and pyrido[2,3-d]pyrimidine N9-C10 reversed-bridge
      antifolates in complex with NADP+ and Pneumocystis carinii dihydrofolate
      reductase.
AB  - Structural studies of two ternary complexes of Pneumocystis carinii dihydrofolate
      reductase (pcDHFR) with the cofactor NADP(+) and potent antifolates, the N9-C10
      reversed-bridge inhibitor 2,4-diamino-6-[N-(2',5'-dimethoxybenzyl)-N
      methylamino]quinazoline (1) and its 3',5'-dimethoxypyrido[2,3-d]pyrimidine analog
      (2), were carried out. Data for the monoclinic crystals were refined to 1.90 A
      resolution for the complex with (1) (R = 0.178) and to 2.1 A resolution for the
      complex with (2) (R = 0.193). The effect of the N9-C10 reversed-bridge geometry
      is to distort the bridge from coplanarity with the pyrido[2,3-d]pyrimidine or
      quinazoline ring system and to twist the C10 methylene conformation toward a
      gauche conformation. This change also influences the conformation of the
      methoxybenzyl ring, moving it away from a trans position. This change places the
      5'-methoxy group deeper within the hydrophobic pocket made by Ile65, Pro66 and
      Phe69 of the pcDHFR active site. These results also revealed the first
      observation of an unusual conformation for the reversed-bridge geometry (C5-C6-N9
      C10 torsion angle) in antifolate (2). The electron density is consistent with the
      presence of two models (conformers 2-1 and 2-2) that result from inversion of the
      geometry at N9. The four examples of N9-C10 reversed-bridge antifolates cluster
      in two conformations, with the structure of quinazoline (1) similar to that
      previously reported for its 2',5'-dimethoxypyrido[2,3-d]pyrimidine analog (3).
      The two conformers of (2) differ from these and each other by a twisted-bridge
      geometry that results in the dimethoxybenzyl ring occupying the same
      conformational space. Conformer 2-2 also has the N9-C10 reversed bridge
      perpendicular to the pyrido[2,3-d]pyrimidine plane, in contrast to the gauche
      trans conformation normally observed. As a result of these changes, the N9 methyl
      probes conformational space in the active site not normally occupied by
      antifolate structures. The N9 methyl of conformer 2-2 makes close contacts to the
      conserved Leu25 as well as the hydroxyl O atoms of the nicotinamide ribose and
      Ser64, whereas the other three reversed-bridge conformers make weak hydrophobic
      contacts with Ile123, Thr61 and Ile65. These antifolates are ten times more
      selective for pcDHFR than the C9-N10 bridge parent trimetrexate. However,
      pyrido[2,3-d]pyrimidines (2) and (3) are three times more selective for pcDHFR
      than quinazoline (1) is for rat liver DHFR. These data suggest that the loss of
      hydrogen-bonding interactions with N8 is more important to potency than the
      interactions of the methoxybenzyl substituents.

PMID- 12198295
TI  - Structure of cyclized green fluorescent protein.
AB  - Crystals of cyclic green fluorescent protein (cGFP) engineered by the previously
      reported split intein technology [Iwai et al. (2001), J. Biol. Chem. 276, 16548
      16554] were obtained and the structure was solved using molecular replacement.
      Although the core of the protein can unambiguously be fitted from the first to
      the last residue of the genuine sequence, the electron density in the region of
      the linker peptide is rather poor owing to the high water content of the
      crystals. Therefore, it is concluded that this part of the protein is highly
      disordered in the present structure and is very flexible. This is supported by
      the absence of crystal contacts in the linker-peptide region and the fact that
      the core of the protein exhibits a very similar conformation to that known from
      other GFP structures, thereby not implicating any constraints arising from the
      presence of the artificial linker. Nevertheless, the density is consistent with
      the loop being intact, as confirmed by mass spectroscopy of dissolved crystals.
      The present structure contains an antiparallel cGFP dimer where the dimer
      interface is clearly different from other crystal structures featuring two GFP
      molecules. This adds further support to the fact that the cylinder surface of GFP
      is rather versatile and can employ various polar and non-polar patches in protein
      protein interactions.

PMID- 12198296
TI  - Metal binding to porcine pancreatic elastase: calcium or not calcium.
AB  - Porcine pancreatic elastase has been crystallized at slightly acidic pH under two
      similar but slightly different conditions. Diffraction data were collected at a
      wavelength of 1.5 A to a maximum resolution of 1.7 A. Both difference electron
      density maps and anomalous difference electron-density maps suggest that in
      crystals grown from a sodium sulfate solution PPE binds Na(+) in its metal
      binding site. In contrast, PPE binds Ca(2+) in crystals grown from a solution
      containing sodium citrate and calcium chloride. This observation is in
      contradiction to most PPE structures reported in the PDB. In addition to the
      metal-binding site, up to three other binding sites, which appear to be anion
      binding sites, could be identified based on the observed anomalous intensity
      differences.

PMID- 12198297
TI  - Xenon derivatization of halide-soaked protein crystals.
AB  - Crystals of porcine pancreatic elastase can be derived by soaking in high
      molarity bromide solutions. These crystals, either in a glycerol-based
      cryoprotectant solution or in paraffin oil, can be subsequently pressurized under
      a xenon atmosphere to incorporate xenon. When paraffin oil is used, a larger
      number of bromide ions are observed on the protein surface. Intensity data
      collected to lower energy than the bromine absorption edge can be used to
      determine the xenon position and the resultant phase information can be used to
      determine the bromine substructure from data collected to higher energy than the
      bromine absorption edge. The method would appear to have general applicability
      where large substructures need to be determined.

PMID- 12198298
TI  - Nonlinear temperature dependence of the crystal structure of lysozyme:
      correlation between coordinate shifts and thermal factors.
AB  - The static and dynamic structures of human lysozyme at seven different
      temperatures ranging from 113 to 178 K were investigated by normal-mode
      refinement of the cryogenic X-ray diffraction data collected from a single
      crystal. Normal-mode refinement decomposes the mean-square fluctuations of
      protein atoms from their average position into the contributions from the
      internal degrees of freedom, which change the shape of the protein structure, and
      those from the external degrees of freedom, which generate rigid-body motions in
      the crystal. While at temperatures below 150 K the temperature dependence of the
      total mean-square fluctuations shows a small gradient similar to that predicted
      theoretically by normal-mode analysis, at temperatures above 150 K there is an
      apparent inflection in the temperature dependence with a higher gradient. The
      inflection in the temperature dependence at temperatures above 150 K occurs
      mostly in the external degrees of freedom. Possible causes for the dynamic
      transition are discussed with respect to the crystal packing and physicochemical
      properties of crystalline water.

PMID- 12198299
TI  - Advantages of high-resolution phasing: MAD to atomic resolution.
AB  - The structure of the endoglucanase A from Clostridium thermocellum CelA was re
      solved by three-wavelength MAD. Experimental phases were obtained in the
      resolution range 25-1.0 A. Various structure-solution approaches were tested in
      order to quantify the contribution of each wavelength. Two-wavelength MAD phasing
      was sufficient to obtain excellent experimental phases. SAD at the remote
      wavelength also resulted in interpretable maps. The three-wavelength MAD electron
      density map was of excellent quality: for parts of the structure, atom types and
      bond types could be easily assigned. Double bonds in peptide links and side
      chains could be located owing to their increased electron density indicating
      their pi character. Comparison with a previously determined structure of CelA at
      1.65 A showed that, apart from a few additional multiple conformers and
      differently oriented side chains, major differences occur at the protein-solvent
      interface. A complete additional solvent shell could be observed and the inner
      shells have been completed. The high accuracy of the structure allowed
      unambiguous assignment of the protonation state for the active-site catalytic
      carboxylates.

PMID- 12198301
TI  - Atomic resolution structure of squash trypsin inhibitor: unexpected metal
      coordination.
AB  - CMTI-I, a small-protein trypsin inhibitor, has been crystallized as a 4:1 protein
      zinc complex. The metal is coordinated in a symmetric tetrahedral fashion by
      glutamate/glutamic acid side chains. The structure was solved by direct methods
      in the absence of prior knowledge of the special position metal centre and
      refined with anisotropic displacement parameters using diffraction data extending
      to 1.03 A. In the final calculations, the main-chain atoms of low B(eq) values
      were refined without restraint control. The two molecules in the asymmetric unit
      have a conformation that is very similar to that reported earlier for CMTI-I in
      complex with trypsin, despite the Met8Leu mutation of the present variant. The
      only significant differences are in the enzyme-binding epitope (including the
      Arg5 residue) and in a higher mobility loop around Glu24. The present crystal
      structure contains organic solvent molecules (glycerol, MPD) that interact with
      the inhibitor molecules in an area that is at the enzyme-inhibitor interface in
      the CMTI-I-trypsin complex. A perfectly ordered residue (Ala18) has an unusual
      Ramachandran conformation as a result of geometrical strain introduced by the
      three disulfide bridges that clamp the protein fold. The results confirm
      deficiencies of some stereochemical restraints, such as peptide planarity or the
      N-C(alpha)-C angle, and suggest a link between their violations and hydrogen
      bonding.

PMID- 12198300
TI  - The 1.45 A resolution structure of the cryptogein-cholesterol complex: a close-up
      view of a sterol carrier protein (SCP) active site.
AB  - Cryptogein is a small 10 kDa elicitor produced by the phytoparasitic oomycete
      Phytophthora cryptogea. The protein also displays a sterol carrier activity. The
      native protein crystallizes in space group P4(1)22, with unit-cell parameters a =
      b = 46.51, c = 134.9 A (diffraction limit: 2.1 A). Its complex with cholesterol
      crystallizes in space group C222(1), with unit-cell parameters a = 30.96, b =
      94.8, c = 65.3 A and a resolution enhanced to 1.45 A. The large inner non
      specific hydrophobic cavity is able to accommodate a large variety of 3-beta
      hydroxy sterols. Cryptogein probably acts as a sterol shuttle helping the
      pathogen to grow and complete its life cycle.

PMID- 12198303
TI  - Crystallization and preliminary X-ray studies of cold-active protein-tyrosine
      phosphatase of Shewanella sp.
AB  - Cold-active protein-tyrosine phosphatase (PTPase) of Shewanella sp. was
      expressed, purified and crystallized using the hanging-drop vapour-diffusion
      method at two different pH values (4.6 and 8.5). Both crystals are orthorhombic
      and belong to space group P2(1)2(1)2(1), with unit-cell parameters a = 56.4, b =
      76.8, c = 81.0 A (pH 8.5) and a = 57.1, b = 77.0 and c = 81.5 A (pH 4.6).
      Diffraction data to 1.82 A for the pH 8.5 crystal and 2.33 A for the pH 4.6
      crystal were collected on a multiwire area detector using a rotating-anode X-ray
      generator.

PMID- 12198302
TI  - Adenovirus proteinase: crystallization and preliminary X-ray diffraction studies
      to atomic resolution.
AB  - Adenovirus proteinase (AVP) is required for the synthesis of infectious virus and
      is a target for antiviral therapy. The enzyme requires two viral cofactors for
      activation: pVIc, an 11-amino acid peptide, and the viral DNA. The structure of
      the enzyme in the absence of cofactors has not been observed. Single crystals of
      AVP were obtained via microseeding using the hanging-drop vapour-diffusion method
      with sodium acetate and sodium citrate as precipitants. At the National
      Synchrotron Light Source at Brookhaven National Laboratory, the native crystal
      diffracted to a resolution of 0.98 A and an isomorphous heavy-atom derivative
      diffracted to 1.9 A. Comparison of the structure of AVP with that of the AVP-pVIc
      complex should reveal the structural basis of activation of the enzyme by pVIc.

PMID- 12198304
TI  - Crystallization and preliminary X-ray diffraction studies of the peptide
      methionine sulfoxide reductase B domain of Neisseria meningitidis PILB.
AB  - Peptide methionine sulfoxide reductases (Msr) are ubiquitous enzymes that
      catalyse the reduction of free and protein-bound methionine sulfoxide back to
      methionine via sulfenic acid chemistry. Two classes of Msrs, MsrA and MsrB, have
      been described. The fact that the two Msrs display opposite stereoselectivities
      and have no sequence identity suggests that there is no structural similarity
      between the two classes. No three-dimensional structure of a MsrB is known. In
      the present report, the MsrB subdomain of Neisseria meningitidis PILB was used to
      grow orthorhombic crystals by the hanging-drop vapour-diffusion technique. The
      crystals belong to space group P2(1)2(1)2(1), with unit-cell parameters a = 44.0,
      b = 118.6, c = 138.5 A. Crystals of selenomethionine-substituted MsrB were grown
      under the same conditions in order to use the MAD method for structure
      determination. Three diffraction data sets at 1.8 A resolution were collected.
      The positions of the Se atoms were determined and should result in a full
      structure determination.

PMID- 12198305
TI  - Crystallization and preliminary X-ray analysis of an R-2-hydroxypropyl-coenzyme M
      dehydrogenase.
AB  - The R-2-hydroxypropyl-coenzyme M (2-mercaptoethanesulfonate) dehydrogenase is a
      key enzyme in the microbial conversion of propylene to the central metabolite
      acetoacetate. This enzyme is an interesting member of the NAD(P)H-dependent short
      chain dehydrogenase/reductase (SDR) family of enzymes, being one of a pair of
      homologous dehydrogenases that act in concert in a single pathway to convert the
      R- and S-enantiomers of hydroxypropyl-coenzyme M to the achiral ketopropyl
      coenzyme M product. Crystallization trials have revealed that the highest
      diffraction quality crystals (better than 2.0 A resolution) could be achieved
      when the reaction substrates were added to the enzyme in a stoichiometric excess
      prior to crystallization.

PMID- 12198306
TI  - Isolation, purification and preliminary X-ray characterization of Cpn60-2 (65 kDa
      heat-shock protein) from Mycobacterium tuberculosis.
AB  - Cpn60-2 is a member of a unique family of putative molecular chaperones
      homologous to GroEL (Cpn60) but of unknown function and found only in
      Mycobacterium tuberculosis and closely related species. Cpn60-2 has mainly been
      studied for its strong immunogenity. Here, the purification, crystallization and
      preliminary crystallographic analysis of M. tuberculosis Cpn60-2 are reported.
      The crystals belong to space group P2, with unit-cell parameters a = 57, b =
      115.5, c = 81.5 A, beta = 95.5 degrees, and contain a dimer in the asymmetric
      unit. The crystals diffract to 4.0 A using a Cu rotating-anode X-ray generator.

PMID- 12198307
TI  - Preliminary X-ray crystallographic analysis of a soluble form of MntC, a
      periplasmic manganese-binding component of an ABC-type Mn transporter from
      Synechocystis sp. PCC 6803.
AB  - Manganese is recruited in microorganisms by way of ABC-type transporter systems.
      Here, the expression, purification and preliminary crystallographic analysis of a
      soluble form of the MntC solute-binding protein component of the MntABC manganese
      import system from the cyanobacterium Synechococystis sp. PCC 6803 is reported.
      The protein (321 amino-acid residues) was expressed exclusively in inclusion
      bodies, which required unfolding and refolding in the presence of manganese prior
      to purification. The purified protein was crystallized in the presence of PEG and
      zinc. The crystals belong to space group P6(2)22, with unit-cell parameters a = b
      = 128.1, c = 90.0 A and a single molecule in the asymmetric unit. The crystals
      diffract to 2.6 A under cryoconditions using synchrotron radiation.

PMID- 12198308
TI  - Crystallization and preliminary crystallographic studies of pyridoxal kinase from
      sheep brain.
AB  - Pyridoxal kinase (ATP:pyridoxal 5'-phosphotransferase; EC 2.7.1.35) is a key
      enzyme in the transformation of vitamin B(6) to pyridoxal-5'-phosphate. Pyridoxal
      5'-phosphate is the crucial cofactor required by numerous enzymes involved in the
      metabolism of amino acids and the synthesis of many neurotransmitters. Pyridoxal
      kinase from sheep brain was crystallized in an orthorhombic form using the
      hanging-drop vapour-diffusion method with sodium citrate as the precipitant. The
      crystals belong to space group P2(1)2(1)2(1), with unit-cell parameters a = 59.8,
      b = 94.4, c = 128.2 A, and diffract to a resolution of 2.1 A. Crystals were
      transferred into a soaking liquid without citrate and two heavy-atom derivatives
      were prepared.

PMID- 12198309
TI  - Crystallization and preliminary crystallographic analysis of a D-aminoacylase
      from Alcaligenes faecalis DA1.
AB  - D-Aminoacylases catalyze the hydrolysis of N-acyl-D-amino acids into D-amino
      acids with the aid of zinc ions. The first D-aminoacylase crystal from
      Alcaligenes faecalis has been obtained in hanging drops at pH 5.6 by the vapour
      diffusion method using 30% polyethylene glycol 4000 as precipitant. It belongs to
      space group P2(1)2(1)2(1), with unit-cell parameters a = 60.2, b = 76.6, c =
      135.3 A. Reflections to 1.2 A resolution are observable. An initial atomic model
      with 472 residues has been built based on SeMet SAD data at 1.8 A resolution.
      Unexpectedly, the structure revealed a novel metal centre in the amidohydrolase
      superfamily.

PMID- 12198310
TI  - Crystallization and preliminary crystallographic study of a ternary complex
      between the T4 phage beta-glucosyltransferase, uridine diphosphoglucose and a DNA
      fragment containing an abasic site.
AB  - A base-flipping phenomenon has been established for DNA methyltransferases and
      for DNA base-excision repair glycosylases and is likely to prove general for
      enzymes that need access to DNA bases to undergo chemical reaction. T4 phage beta
      glucosyltransferase (BGT) is a good candidate for this novel mechanism. In order
      to confirm this, BGT was crystallized with an abasic site-containing DNA and
      uridine diphosphoglucose (UDP-glucose). The crystallization strategy is
      described. A complete data set was collected at 1.8 A resolution on a Cu Kalpha
      rotating-anode X-ray source. Molecular replacement was performed and the initial
      electron-density maps clearly show bound DNA.

PMID- 12198311
TI  - Crystallization and preliminary X-ray diffraction studies of the complete modular
      endolysin from Cp-1, a phage infecting Streptococcus pneumoniae.
AB  - Endolysin from the phage Cp-1 (Cpl-1) cleaves the glycosidic beta1,4-bonds
      between the N-acetylmuramic acid and the N-acetylglucosamine of the pneumococcal
      cell wall. Cpl-1 has been crystallized using the hanging-drop vapour-diffusion
      method at 291 K. Diffraction-quality orthorhombic crystals of the native protein
      were obtained only after addition of the detergent n-decyl-beta-D-maltoside.
      Crystals belong to space group C222(1), with unit-cell parameters a = 77.949, b =
      95.782, c = 129.282 A. Diffraction data to a resolution of 2.1 A were collected
      at a synchrotron facility.

PMID- 12198312
TI  - Spore-coat laccase CotA from Bacillus subtilis: crystallization and preliminary X
      ray characterization by the MAD method.
AB  - Bacterial endospores are highly resistant structures that allow survival for long
      periods of time in adverse environments. The spore-forming Gram-positive
      bacterium Bacillus subtilis synthesizes a coat around the endospore during
      development composed of several assembled polypeptides. The role of these
      components of the spore coat remains unclear; however, some of them appear to be
      enzymes possibly involved in the assembly process or in the final properties of
      the spore. The outer spore-coat protein CotA is a 65 kDa polypeptide showing a
      high degree of sequence similarity with copper-dependent oxidases, including
      fungal and plant laccases, ascorbate oxidase and CueO from Esherichia coli. CotA
      has been recently characterized as a copper-dependent laccase. Unlike previously
      reported laccases, CotA shows increased thermostability. Here, the
      crystallization of a recombinant CotA protein produced in E. coli and the
      preliminary characterization of the crystals is reported. Structure solution by
      the MAD method at the copper K edge is also reported.

PMID- 12198313
TI  - Crystallization and preliminary X-ray analysis of a xylanase from the
      psychrophile Pseudoalteromonas haloplanktis.
AB  - The 46 kDa xylanase from the Antarctic microorganism Pseudoalteromonas
      haloplanktis is an enzyme that efficiently catalyzes reactions at low
      temperatures. Here, the crystallization of both the native protein and the SeMet
      substituted enzyme and data collection from both crystals using synchrotron
      radiation are described. The native data showed that the crystals diffract to 1.3
      A resolution and belong to space group P2(1)2(1)2(1), with unit-cell parameters a
      = 50.87, b = 90.51, c = 97.23 A. SAD data collected at the peak of the selenium
      absorption edge proved to be sufficient to determine the heavy-atom configuration
      and to obtain electron density of good quality.

PMID- 12198314
TI  - Purification, crystallization and initial crystallographic analysis of RNA
      polymerase holoenzyme from Thermus thermophilus.
AB  - RNA polymerase holoenzyme from Thermus thermophilus, consisting of six protein
      subunits (alpha(2), beta, beta', omega and sigma(70)) and having a total
      molecular mass of about 450 kDa, was purified and crystallized by the hanging
      drop vapour-diffusion technique under mild near-physiological conditions. The
      crystals diffract beyond 3 A resolution. Careful analysis of diffraction data
      revealed that the crystals belong to space group P3(2), with unit-cell parameters
      a = b = 236.35, c = 249.04 A, and have perfect twinning along the threefold axis.
      A complete data set at 3 A resolution was collected and an unambiguous molecular
      replacement solution was found using the structure of T. aquaticus RNA polymerase
      core enzyme as a search model. The refinement of structure and model building of
      the sigma(70) subunit is now in progress.

PMID- 12198315
TI  - Crystallization and preliminary X-ray data of a bifunctional peroxiredoxin from
      poplar.
AB  - Two variants (wild type and V152C mutant) of a bifunctional poplar peroxiredoxin
      have been overexpressed in Escherichia coli cells. The two recombinant enzymes
      were purified and crystallized using the hanging-drop vapour-diffusion technique.
      Data sets were collected to 1.62 and 2.48 A resolution using X-ray synchrotron
      source radiation from two crystal forms of wild-type peroxiredoxin which belonged
      to the monoclinic space group P2(1) (with unit-cell parameters a = 59.26, b =
      68.80, c = 75.71 A, beta = 93.45 degrees ) and to the orthorhombic space group
      P2(1)2(1)2 (with unit-cell parameters a = 64.70, b = 130.73, c = 35.59 A),
      respectively. Data were also collected to 2.17 A resolution using a home X-ray
      source from a V152C peroxiredoxin crystal which belongs to the triclinic space
      group (P1), with unit-cell parameters a = 36.65, b = 41.53, c = 58.06 A, alpha =
      70.52, beta = 93.45, gamma = 64.31 degrees. Phases have been obtained using
      molecular replacement with the structure of human peroxiredoxin V (PDB code 1hd2)
      as a search model. Refinement of the structures is in progress.

PMID- 12198316
TI  - Cloning, purification, crystallization and preliminary X-ray analysis of DOS heme
      domain, a new heme oxygen sensor in Escherichia coli.
AB  - The heme-containing PAS domain of the direct oxygen-sensor protein (DOS(H)), a
      bona fide oxygen-sensor protein, has been cloned from Escherichia coli strain K12
      and successfully purified. The oxidized form of this protein was crystallized by
      the hanging-drop method with a PEG 8000-based precipitant. Preliminary X-ray
      diffraction studies of the PAS-domain crystal show that it belongs to the
      orthorhombic space group P2(1)2(1)2(1), with unit-cell parameters a = 46.1, b =
      68.1, c = 82.6 A. A complete diffraction data set was collected to 1.9 A for MAD
      phasing. The electron-density map shows two molecules in an asymmetric unit and a
      unique six-coordination of the heme iron.

PMID- 12198317
TI  - Crystallization and preliminary X-ray study of recombinant betaine-homocysteine S
      methyltransferase from rat liver.
AB  - Betaine-homocysteine S-methyltransferase is one of the three enzymes involved in
      homocysteine catabolism. It uses betaine as the methyl donor to convert
      homocysteine into methionine, also producing dimethylglycine. Recombinant BHMT
      from rat liver was crystallized by the vapour-diffusion method in both native and
      seleniomethionyl-labelled forms. Crystals belong to space group P2(1), with unit
      cell parameters a = 57.8, b = 149.3, c = 96.2 A, beta = 92.9 degrees. Data from
      native, seleniomethionine-labelled and two heavy-atom derivatives were collected
      using synchrotron sources. Self-rotation function and sedimentation-velocity
      experiments suggest that the enzyme is tetrameric with 222 symmetry.

PMID- 12198318
TI  - Mechanisms of action of novel cardiotonic agents.
AB  - Regulation of myocardial contractility by cardiotonic agents is achieved by an
      increase in intracellular Ca2+ mobilization (upstream mechanism), an increase in
      Ca2+ binding affinity to troponin C (central mechanism), or facilitation of the
      process subsequent to Ca2+ binding to troponin C (downstream mechanism). cAMP
      mediates the regulation induced by Ca2+ mobilizers such as beta-adrenoceptor
      agonists and selective phosphodiesterase III inhibitors acting through the
      upstream mechanism. These agents act likewise on the central mechanism to
      decrease Ca2+ sensitivity of troponin C in association with the cAMP-mediated
      phosphorylation of troponin I. In addition to such a well-known action of cAMP,
      recent experimental findings have revealed that Ca2+ sensitizers, such as
      levosimendan, OR-1896, and UD-CG 212 Cl, require the cAMP-mediated signaling for
      induction of Ca2+ sensitizing effect. These agents shift the [Ca2+] -force
      relationship to the left, but their positive inotropic effect (PIE) is inhibited
      by carbachol, which suppresses selectively the cAMP-mediated PIE. These findings
      imply that cAMP may play a crucial role in increasing the myofilament Ca2+
      sensitivity by cross-talk with the action of individual cardiotonic agents. No
      clinically available cardiotonic agents act primarily via Ca2+ sensitization, but
      the PIE of pimobendan and levosimendan is partly mediated by an increase in
      myofilament Ca2+ sensitivity. Evidence is accumulating that cardiotonic agents
      with Ca2+ sensitizing action are more effective than agents that act purely via
      the upstream mechanism in clinical settings. Further clinical trials are required
      to establish the effectiveness of Ca2+ sensitizers in long-term therapy for
      congestive heart failure patients.

PMID- 12198319
TI  - Time-dependent cardioprotection with calcium antagonism and experimental studies
      with clevidipine in ischemic-reperfused pig hearts: part II.
AB  - The intracellular calcium level is increased during ischemia and early
      reperfusion. The aim of this study was to study the role of the calcium influx in
      the development of myocardial ischemic and reperfusion injury during the early
      and late phases of ischemia and during early reperfusion. An ultrashort-acting
      calcium antagonist, clevidipine, was used as a tool for this investigation.
      Pentobarbital-anesthetized pigs were subjected to 45 minutes of LAD occlusion
      followed by 240 minutes of reperfusion. In the first set of experiments,
      clevidipine (0.3 nmol/kg per minute) was infused over 5 minutes into the ischemic
      myocardium via a catheter in the LAD, starting at 5, 35, or 44 minutes following
      the onset of ischemia (n = 6 in each group). The area at risk and the infarct
      size were determined after 240 minutes of reperfusion by staining with Evans blue
      dye and triphenyl tetrazolium chloride (TTC), respectively. In a second set of
      experiments, two groups of animals (n = 6 in each) were subjected to the same
      periods of ischemia and reperfusion; one group received no infusion during
      ischemia, whereas the other group received vehicle infusion during a 5-minute
      period between 5 and 10 minutes of ischemia. In the first set of experiments,
      there were no significant differences between the groups with regard to
      hemodynamic variables. The area at risk expressed as a percentage of the left
      ventricle was of similar magnitude in all three clevidipine-treated groups (about
      18%). The infarct size, expressed as a percentage of the area at risk, was
      significantly smaller in pigs given clevidipine after 5 minutes (58 +/- 17%; p <
      0.01) and after 44 minutes (42 +/- 6%; p < 0.01) of ischemia than in pigs
      receiving clevidipine after 35 minutes of ischemia (85 +/- 4%). The difference in
      infarct size between pigs given clevidipine after 5 or 44 minutes of ischemia was
      not significant. In the second set of experiments, there was a similar area at
      risk and no significant difference in infarct size between the noninfusion group
      and the 5-minute vehicle infusion group, indicating that the LAD infusion per se
      did not affect infarct size. The present results demonstrate that blockade of
      calcium influx by the short-acting dihydropyridine calcium antagonist clevidipine
      during the early phase of ischemia and at the time of reperfusion, but not during
      a late phase of ischemia, limits infarct size induced by ischemia and
      reperfusion. This indicates that the pathophysiological importance of calcium
      influx varies according to the different phases of myocardial ischemia and
      reperfusion.

PMID- 12198321
TI  - Melatonin potentiates phenylephrine-stimulated intracellular Ca2+ transient in
      smooth muscle cell of large arteries of chick embryo.
AB  - In the current study we first characterized the properties of the 2
      [125I]iodomelatonin binding in pulmonary artery and aorta of chick embryo, and
      then determined the location of the binding site with autoradiography. Receptor
      binding assays were used using 2-[125I]iodomelatonin as ligand. The binding was
      stable, saturable, specific and reversible. Scatchard anlaysis revealed an
      equilibrium binding constant (Kd) of 27.12 +/- 1.34 pM and a maximum binding
      capacity (Bmax) of 1.93 +/- 0.19 fmol/mg protein (n = 5). Guanosine 5'-O-(3
      thiotriphosphate) (GTPgammaS) increased the Kd, but reduced the Bmax, indicating
      the binding being coupled to a G-protein. Autoradiography revealed the binding
      sites in the smooth muscle layer. To delineate the physiological function of
      melatonin in the large artery of the chick embryo, we determined the
      intracellular calcium ([Ca2+]i) in smooth muscle cells of the aorta with
      spectrofluorometry, using fura 2-AM as calcium indicator. Melatonin at 10(-8) to
      10(-5), which itself had no effect, potentiated the stimulating effect of 0.1
      microM phenylephrine, a selective agonist of alpha -adrenoceptor, on [Ca2+]i. In
      conclusion, specific binding of 2-[125I]iodomelatonin and physiological response
      to melatonin suggest the existence of melatonin receptor in the smooth muscle of
      large arteries of the chick embryo. Melatonin potentiates the effects of alpha1
      adrenergic stimulation.

PMID- 12198320
TI  - Anti-ischemic compound KC 12291 prevents diastolic contracture in isolated atria
      by blockade of voltage-gated sodium channels.
AB  - Several lines of evidence support a fundamental role for voltage-gated sodium
      channels in mediating ischemic Na rise. We examined the effect of the novel anti
      ischemic compound KC 12291 on veratridine-stimulated and lysophosphatidylcholine
      (LPC)-induced sustained sodium current (I(NAL)) mediated by sodium channels in
      isolated myocytes obtained from guinea-pig atria, by using the whole-cell patch
      clamp technique. We also analyzed the effect of KC 12291 on veratridine- and LPC
      induced contractures in isolated guinea-pig atria. Veratridine as well as LPC
      increased I(NAL) measured at 20 ms of a 2 s pulse evoked from -100 to -30 mV
      (47.5 and 12 pA/pF in the presence of 40 microM veratridine and 10 microM LPC,
      respectively, vs. 6.7 pA/pF under control conditions). A significant reduction by
      KC 12291 in the quantity of charge carried by veratridine-stimulated I(NAL) in
      the range of test potentials between -50 mV and +10 mV was observed and similar
      effects were obtained on LPC-induced I(NAL). Thus, the quantity of charge carried
      by LPC-induced I(NAL) over a 2 s pulse to -30 mV was reduced by 48% in the
      presence of 10 microM KC 12291 vs. a reduction by 50% of veratridine-stimulated
      I(NAL) at the same test potential. Veratridine- and LPC-induced submaximal
      contractures in isolated atria were significantly inhibited by KC 12291 in a
      concentration-dependent manner, with an IC of 0.55 microM and 0.79 microM,
      respectively. The data indicate that veratridine- and LPC-induced increases in
      diastolic tension are inhibited by KC 12291 by a mechanism that involves blockade
      of voltage-gated sodium channels mediating sustained sodium current.

PMID- 12198322
TI  - Chronic mu-opioid receptor stimulation alters cardiovascular regulation in
      humans: differential effects on muscle sympathetic and heart rate responses to
      arterial hypotension.
AB  - In opioid addicted patients, respiratory regulation adapts allowing intake of
      otherwise lethal dosages of opioids. In contrast, little is known about
      cardiovascular regulation during chronic opioid receptor stimulation. We
      previously demonstrated that chronic mu-opioid receptor stimulation by methadone
      decreases resting muscle sympathetic activity (MSA). However, for short-term
      control of arterial blood pressure autonomic responses to arterial hypotension
      may be of greater importance. Accordingly, we tested the hypothesis that chronic
      opioid receptor stimulation attenuates muscle sympathetic and heart rate
      responses to arterial hypotension. Ten young patients (mean +/- SD, 30 years +/-
      6) with a long history of mono-opioid addiction and under oral methadone
      substitution therapy (54 mg d(-1) +/- 31) for 12 months (+/-20) were studied.
      Peroneal MSA (microneurography) and heart rate responses to hypotensive
      challenges (sodium nitroprusside) were assessed in the awake state and compared
      with those of 10 matched healthy subjects. Effects of mu-opioid receptor blockade
      by naloxone (12.4 mg i.v.) were determined during propofol anesthesia. Chronic mu
      opioid receptor stimulation markedly decreased the MSA response to hypotension (
      0.5 units mm Hg(-1) +/- 0.2 vs. -2.0 +/- 1.8; p = 0.01) compared with healthy
      subjects despite similar arterial blood pressure and heart rate at rest. In
      contrast, the heart rate response to hypotension did not differ between addicted
      patients (6 ms mm Hg(-1) +/- 2) and healthy subjects (7 ms mm Hg(-1) +/-4).
      Opioid receptor blockade during propofol anesthesia markedly increased the MSA
      response to hypotension even beyond awake values (-1.2 units mm Hg(-1) +/- 1.1; p
      = 0.02 vs. awake) while the heart rate response remained unchanged. Thus, chronic
      mu-opioid receptor stimulation 1) results in uncompensated depression of
      cardiovascular sympathetic neural regulation, and 2) exerts differential effects
      on efferent sympathetic nerve activity to muscle and on heart rate control in
      response to arterial hypotension.

PMID- 12198323
TI  - Restored capillary density in spared myocardium of infarcted rats improves
      ischemic tolerance.
AB  - Myocardial infarction (MI)-induced hypertrophy is associated with a decreased
      capillary density, which may negatively affect ischemic tolerance of the spared
      myocardium. The current study investigated the effects of moxonidine, a centrally
      acting sympatholytic, on left ventricular (LV) hypertrophy and capillary density
      in relation to sensitivity to ischemia in infarcted hearts. Infarcted rats were
      randomized to receive 3 or 6 mg/kg/d of moxonidine from 1 to 21 days after MI. LV
      hypertrophy after MI was indicated by increased ventricular to body weight ratio
      and was significantly inhibited by moxonidine. Histologic analysis revealed that
      MI-induced concentric hypertrophy of the spared myocardium, as indicated by
      almost double cross-sectional area of Gomori-stained myocytes, was completely
      prevented by 6 mg/kg/d of moxonidine. This effect was accompanied by a a restored
      number of lectin-stained capillaries per tissue area. However, capillary-to
      myocyte ratio was similar in all groups. LV dysfunction after MI, measured in
      isolated perfused hearts, was confirmed by decreased LV systolic pressure and
      +dP/dtmax and was not affected by moxonidine. Low-flow ischemia, induced by
      lowering perfusion pressure from 85 to 15 mm Hg for 30 min, resulted in a further
      reduction of cardiac perfusion compared with sham rats, which was normalized with
      6 mg/kg/d of moxonidine. Ischemic sensitivity in MI hearts, as reflected by
      increased maximal coronary flow during reperfusion, was reduced with moxonidine.
      This was further supported by substantially lower purines and lactate
      concentrations in the coronary effluent during ischemia. These results indicate
      that moxonidine-induced prevention of hypertrophy may preserve capillary density
      without affecting capillary number, thereby improving ischemic tolerance of the
      spared myocardium.

PMID- 12198324
TI  - Angiotensin II type 1 receptor blockade restores nitric oxide-dependent renal
      vascular responses in renovascular hypertension.
AB  - It was previously reported that enhancement of renal vascular responses to
      angiotensin II in hypertensive rats is related to decreased release of nitric
      oxide. Thus, it was suggested that impairment of nitric oxide synthesis during
      development of hypertension is related to a decreased nitric oxide synthase mRNA
      expression by an angiotensin II-dependent mechanism. The current study evaluated
      whether the blockade of angiotensin II type 1 receptor during the development of
      hypertension restored nitric oxide synthase mRNA expression, nitric oxide
      synthesis, and nitric oxide-dependent modulation of angiotensin II
      vasoconstrictor effects. It was shown that losartan treatment prevented increased
      vascular responses to angiotensin II in hypertensive rats and that this effect
      was associated with restoration of nitric oxide synthase mRNA expression and
      nitric oxide synthase activity. Furthermore, angiotensin II-dependent nitric
      oxide release in hypertensive rats was potentiated by losartan treatment.
      Angiotensin II (1 microg) released renal nitrites by 485 +/- 178, 470 +/- 150,
      185 +/- 45, and 515 +/- 100 nmol/ml/30 s in the kidneys from normotensive,
      losartan-treated normotensive rats, hypertensive, and losartan-treated
      hypertensive rats, respectively. The data suggest that during development of
      hypertension, angiotensin II downregulates nitric oxide synthase mRNA expression,
      blunting nitric oxide vasodilatory tone and increasing vascular sensitivity to
      vasoconstrictor agents in the renal circulation.

PMID- 12198325
TI  - Dose-dependent prevention of fibrosis in aorta of salt-loaded stroke-prone
      spontaneously hypertensive rats by combined delapril and indapamide treatment.
AB  - Combined treatment with the angiotensin-converting enzyme (ACE) inhibitor
      delapril and the diuretic indapamide prevented vascular damage in vital organs of
      salt-loaded stroke-prone spontaneously hypertensive rats (SHRsp). Whether the
      changes occurring after long-term hypertension could also be modulated in large
      arteries was investigated. Two-month-old SHRsp were salt loaded and treated with
      the drug regimen until they reached 50% mortality or around midlife. In a first
      experiment, delapril (12 mg/kg) and indapamide (1 mg/kg) were administered daily
      separately or in combination. In the second dose-finding experiment, delapril (6,
      3, 1.5 mg/kg) and indapamide (0.5, 0.25, 0.125 mg/kg) in decreasing dose
      combinations were analyzed. Ultrastructural, histomorphometric, and biochemical
      studies were performed on the thoracic aorta. When compared with delapril (12
      mg/kg) or indapamide (1 mg/kg) administered individually for 5 months, the
      combination 12 + 1 mg/kg was able to prevent the increase in extracellular matrix
      deposition observed in other treatment groups, as assessed by histomorphometry or
      4-OH-proline biochemical determination. In the second experiment, a half-dose
      (delapril 6 mg/kg + indapamide 0.5 mg/kg) combination was similarly effective in
      counteracting fibrosis, but the other doses progressively failed. In the first
      experiment, the combination had a stabilizing effect on hypertension and
      stimulated diuresis. In the second experiment, arterial blood pressure values and
      sodium balance were not consistently affected by the treatments that antagonized
      fibrosis (i.e., delapril 6 mg/kg + indapamide 0.5 mg/kg and, less efficiently,
      delapril 3 mg/kg + indapamide 0.25 mg/kg). These results suggest that indapamide
      interacts with ACE inhibitors to limit aortic fibrosis independent of any well
      established mechanism.

PMID- 12198326
TI  - Dietary phytoestrogens and their synthetic structural analogues as calcium
      channel blockers in human platelets.
AB  - Phytoestrogens have been shown to inhibit platelet activation by blocking
      platelet calcium channels. This study examined the effect of several synthetic
      derivatives of trans-resveratrol, genistein, and daidzein on platelet free
      intracellular calcium ([Ca2+]i) elevation in thrombin-activated platelets and the
      possible mechanisms of this inhibitory effect. Studies were conducted on fresh
      human platelets from healthy volunteers. The fluorescent dye fura-2 was used to
      monitor [Ca2+]i in platelets. At 10 microM-resveratrol, triacetyl-trans
      resveratrol, and trimethoxy-trans-resveratrol produced, respectively, 57 +/- 4%,
      40 +/- 4%, and 21 +/- 1% inhibition; genistein, acetylgenistein, and
      dihydrogenistein produced 51 +/- 10%, 26 +/- 7%, and 16 +/- 2% inhibition,
      respectively; daidzein and diacetyldaidzein produced 56 +/- 5% and 45 +/- 10%
      inhibition of thrombin-induced [Ca2+]i elevation. The inhibitory effect was
      immediate and appeared to directly affect the calcium influx channels.
      Phytoestrogen action on [Ca2+]i did not cause alteration in nitric oxide
      signaling. Tyrosine phosphorylation was not involved in the inhibition of [Ca2+]i
      elevation by phytoestrogens, because the percent inhibition produced by the
      tyrosine kinase inhibitor genistein and its inactive analogue daidzein on
      thrombin-induced and thapsigargin-induced [Ca2+]i elevation was not significantly
      different for either compound at any concentration tested. Structure-activity
      relationship studies on this limited set of compounds reveal the requirements for
      the stilbene pharmacophore for the calcium-blocking activity.

PMID- 12198327
TI  - Effects of chronic subdepressor dose of angiotensin II type 1 receptor antagonist
      on endothelium-dependent vasodilation in patients with congestive heart failure.
AB  - Angiotensin II type 1 receptor antagonist (AIIRA) has been reported to improve
      exercise capacity and prognosis in patients with congestive heart failure (CHF).
      However, the effects of AIIRA on peripheral endothelium-dependent and 
      independent vasodilation remain undefined in this disorder. This study examined
      the effects and the mechanism of chronic AIIRA therapy on peripheral vasomotion
      in CHF. Twenty-six patients with CHF were recruited for this study. In protocol
      1, 20 patients with CHF were randomly assigned into a losartan (AIIRA) group (n =
      10) and a placebo group (n = 10). Forearm blood flow (FBF; ml/min per 100 ml
      tissue) changes induced by intra-arterial infusion of acetylcholine, sodium
      nitroprusside, and synthetic angiotensin II were determined by plethysmography
      before and 3 months after administration of a subdepressor dose of AIIRA or
      placebo. The goal of protocol 2 was to determine whether the effect of AIIRA is
      due to a nitric oxide-dependent mechanism in the remaining subset of the CHF
      group (n = 6). In this group, FBF responses to acetylcholine were examined with
      and without coadministration of a nitric oxide synthase inhibitor (N(G)
      monomethyl->L-arginine; >L-NMMA) either before and 3 months after AIIRA therapy.
      No significant differences were found in changes in systemic blood pressure and
      basal FBF among patient groups during the study period. In protocol 1, although
      in both groups FBF responses induced by sodium nitroprusside as well as
      angiotensin II remained constant throughout the study, acetylcholine-induced FBF
      response was significantly enhanced in the losartan group (p < 0.05) but not in
      the placebo group. In protocol 2, acetylcholine-induced FBF response without >L
      NMMA was significantly enhanced after AIIRA administration (p < 0.05), whereas
      this augmentation effect was diminished under >L-NMMA coinfusion. In conclusion,
      selective administration of an AIIRA for 3 months improves peripheral endothelium
      dependent dilation in patients with CHF. This mechanism may be independent of
      direct AIIRA effects and may be due, in part, to increased bioavailability of
      nitric oxide.

PMID- 12198328
TI  - Susceptibility to cardiac ischemia/reperfusion injury is modulated by chronic
      estrogen status.
AB  - The purpose of this study was to test whether the susceptibility of the heart to
      ischemia/reperfusion injury is modulated by the chronic estrogen status, i.e.,
      increased with estrogen deficiency and attenuated by pharmacologic estrogen
      supplementation. In addition, the study tested whether estrogen-dependent changes
      in mechanical function are associated with alterations of cardiac high-energy
      phosphate metabolism. Rats were ovariectomized, not ovariectomized, or
      ovariectomized and treated with subcutaneous estrogen pellets (1.5 mg/21 d) (n =
      8-11 per group). Three weeks later, hearts were isolated and perfused
      isovolumically under constant perfusion pressure conditions. Hearts were
      subjected to 15 min of total global ischemia (37 degrees C) and 30 min of
      reperfusion. Simultaneous [31P] nuclear magnetic resonance spectra were recorded
      throughout this protocol to monitor changes in ATP, phosphocreatine, and
      inorganic phosphate content. Whereas preischemic values for heart rate, end
      diastolic pressure, and coronary flow were not different among groups, left
      ventricular developed pressure was slightly but significantly decreased in the
      estrogen-treated group (p < 0.05). However, treated hearts showed improved
      recovery of left ventricular developed pressure on reperfusion (89 +/- 4% in
      control rats, 70 +/- 8% in ovariectomized hearts, and 114 +/- 9% of preischemic
      values in estrogen-treated rats). However, changes in ATP, phosphocreatine, and
      inorganic phosphate during ischemia were as previously described and were
      unaffected by chronic estrogen status. In conclusion, in the isolated buffer
      perfused rat heart, estradiol treatment caused improved functional recovery after
      ischemia/reperfusion injury. This improvement, however, did not include
      preservation of high-energy phosphate metabolism. Other potential mechanisms
      include an anti-oxidant activity of 17beta-estradiol-and estrogen-induced
      alterations in glucose metabolism.

PMID- 12198329
TI  - Cardioprotection from ischemia/reperfusion induced by red wine extract is
      mediated by K(ATP) channels.
AB  - The objective was to analyze the mechanism of the protection induced by a
      nonalcoholic extract of red wine (RWE) on ischemia/reperfusion injury. Isovolumic
      perfused rat hearts were exposed after stabilization to a 20-min global ischemic
      period followed by 30 min of reperfusion in absence and presence of RWE infused
      prior to ischemia and early in reperfusion. In other hearts, 5-hydroxydecanoate
      (5-HD, 100 microM), a selective mitochondrial K(ATP) blocker, chelerythrine (1
      microM), a protein kinase C blocker, or >L(G)-nitro->L-arginine methyl ester (>L
      NAME), a nitric oxide synthase inhibitor, was administered prior to RWE infusion.
      Left ventricular developed pressure (LVDP), +dP/dtmax, and left ventricular end
      diastolic pressure (LVEDP) were used to assess myocardial function. The lactate
      dehydrogenase release during reperfusion was measured. After the ischemic period,
      LVDP decreased to 61 +/- 4% and +dP/dtmax to 62 +/- 5% of baseline values at the
      end of reperfusion. The infusion of RWE resulted in a complete recovery of
      systolic function (LVDP = 102 +/- 4%; +dP/dtmax = 101 +/- 4%) and in an
      attenuation of the increase of LVEDP (20 +/- 3 mm Hg versus 42 +/- 4 mm Hg, p <
      0.05). The treatment with RWE did not produce lactate dehydrogenase release
      during reperfusion. 5-HD and chelerythrine completely abolished the protection
      induced by RWE (mechanical and enzymatic). >L-NAME partially abolished the
      systolic improvement induced by RWE but returned lactate dehydrogenase loss to
      ischemic control values. The diastolic protection afforded by RWE was not altered
      by >L-NAME. These data are the first demonstration that mitochondrial K channels
      and nitric oxide are involved in the protection against ischemia/reperfusion
      conferred by a nonalcoholic RWE.

PMID- 12198330
TI  - Characterization of Ca2+ channels involved in endothelin-1-induced contraction of
      rabbit basilar artery.
AB  - This study attempted to characterize Ca2+ channels involved in endothelin-1
      induced contraction of rabbit basilar artery using whole-cell patch-clamp and
      measurement of intracellular free Ca2+ concentration. Endothelin-1 activates two
      types of Ca2+-permeable nonselective cation channels (NSCC-1 and NSCC-2) and a
      store-operated Ca2+ channel (SOCC) in addition to the voltage-operated Ca2+
      channel (VOCC). These channels can be discriminated using Ca2+ channel blockers,
      SK&F 96365 and LOE 908. Tension study was conducted to clarify the Ca2+ channels
      involved in endothelin-1-induced contraction of basilar artery. Endothelin-1
      induced basilar artery contraction is fully dependent on extracellular Ca2+
      influx. Based on sensitivity to nifedipine, an L-type VOCC blocker, VOCCs have a
      minor role in endothelin-1-induced contraction. Both LOE 908 and SK&F 96365
      inhibit endothelin-1-induced contraction in a concentration-dependent manner, and
      their combination abolished it. The median inhibitory concentrations of these
      blockers for endothelin-1-induced contraction correlated well with those of the
      endothelin-1-induced [Ca2+]i responses. Thus, the inhibitory action of these
      blockers on endothelin-1-induced contraction may be mediated by blockade of NSCC
      1, NSCC-2, and the SOCC. Extracellular Ca2+ influx through NSCC-1, NSCC-2, and
      SOCC may be essential for endothelin-1-induced basilar artery contraction.

PMID- 12198332
TI  - Endothelial and neuronal functions in cerebral and temporal arteries from monkeys
      fed a high-cholesterol diet.
AB  - Modifications by hyperlipidemia of endothelium-dependent and -independent
      relaxations were evaluated in cerebral and temporal arteries from control and
      hyperlipidemic (high cholesterol-fed) monkeys. Histologically atherosclerotic
      lesions were not observed in either group. Relaxations induced by histamine,
      abolished by N(G)-nitro->L-arginine (>L-NA), were significantly potentiated in
      the hyperlipidemic monkey cerebral arteries, compared with those in the arteries
      from control monkeys. Treatment with superoxide dismutase did not affect the
      histamine-induced relaxation. Conversely, endothelium-dependent relaxations
      induced by A23187, Ca2+ ionophore, in cerebral arteries did not differ between
      control and hyperlipidemic monkeys. In temporal arteries, relaxations by
      acetylcholine and A23187 did not differ between control and hyperlipidemic
      monkeys. Endothelium-dependent and -independent relaxations by adenosine
      diphosphate in cerebral and temporal arteries were not affected by
      hyperlipidemia. Endothelium-independent relaxations by exogenously applied nitric
      oxide did not differ in the arteries from control and hyperlipidemic monkeys.
      Nicotine-induced relaxations in cerebral arteries, which were mediated with
      nitric oxide released from nitroxidergic (nitrergic) nerves, and the contractions
      caused by nicotine in temporal and mesenteric arteries treated with >L-NA did not
      differ between control and hyperlipidemic monkeys. It is concluded that long
      exposure to hyperlipidemia did not affect endothelial functions of monkey middle
      cerebral and temporal arteries but enhanced nitric oxide-mediated relaxations
      caused by histamine, possibly due to upregulation of endothelial histamine
      receptor-mediated functions in the cerebral arteries. The nitroxidergic
      (nitrergic) and adrenergic nerve functions do not seem to be affected by
      hyperlipidemia.

PMID- 12198331
TI  - Chronic infusion of beta-adrenoceptor antagonist and inverse agonists decreases
      elevated protein kinase A activity in transgenic mice with cardiac-specific
      overexpression of human beta 2-adrenoceptor.
AB  - Neutral antagonists and inverse agonists can produce different cellular responses
      in some systems. The effects of chronic (14-day) infusion of three ligands, ICI
      118,551, carvedilol, and alprenolol were examined in cardiac tissue from wild
      type and transgenic mice with cardiac-specific overexpression of the human beta2
      adrenoceptor. These ligands vary in their negative efficacy at the human beta2
      adrenoceptor, with two (ICI-118,551 and carvedilol) behaving as inverse agonists
      and one (alprenolol) behaving as a neutral antagonist. Cardiac tissue from the
      transgenic mice exhibited elevated levels of protein kinase A activity and G
      protein receptor kinase-2. Fourteen-day infusions of the three ligands lowered
      the elevated levels of protein kinase A activity of the transgenic hearts to
      control levels. Alprenolol and carvedilol also decreased G protein receptor
      kinase-2 amounts to control levels. The left atria from transgenic mice exhibited
      an impaired inotropic response to histamine relative to responses of wild-type
      mice atria. Infusions of the inverse agonists and a neutral antagonist at the
      beta2-adrenoceptor significantly restored the impaired histamine response.
      Restoration of protein kinase A activity and the impaired histamine responses in
      the atria from transgenic mice can be observed following 14-day infusions of both
      a neutral antagonist and inverse agonists. The reversal of the effects of the
      transgene by both inverse agonists and a neutral antagonist suggests that agonist
      occupancy, and not spontaneous activity, of the beta2-adrenoceptor is producing
      the elevated protein kinase A activity and the impaired histamine response.

PMID- 12198333
TI  - Endothelium-dependent hyperpolarization to acetylcholine in carotid artery of
      guinea pig: role of lipoxygenase.
AB  - This study was designed to determine whether lipoxygenase-dependent metabolites
      of arachidonic acid are involved in the endothelium-dependent hyperpolarization
      of the guinea pig carotid artery. The membrane potential of vascular smooth
      muscle cells was measured with intracellular microelectrodes and potassium
      channels were studied on freshly isolated cells with the patch-clamp technique.
      Acetylcholine-induced hyperpolarizations were not affected by arachidonyl
      trifluoromethyl ketone (AACOCF3), quinacrine (phospholipase A inhibitors), or
      eicosatetraenoic acid (nonspecific inhibitor of lipoxygenase, cytochrome P450,
      and cyclooxygenase). In contrast, cinnamyl-3,4 dihydroxy-alpha-cyanocinnamate
      (CDC) and AA861 (lipoxygenase inhibitors) as well as 1-(6-(17beta-3-methoxyestra
      1,3,5(10)-trien-17-yl)amino) hexyl)-1H-pyrrole-2,5-dione (U-73122) (phospholipase
      C inhibitor) produced a significant inhibition of the hyperpolarization. An
      opener of intermediate conductance calcium-activated potassium channels, 1-ethyl
      2-benzamidazolinone (1-EBIO), induced a hyperpolarization that was unaffected by
      AACOCF3, CDC, AA861, or U-73122 but was inhibited by charybdotoxin. (+/-)12
      hydroxy-eicosatetraenoic acid (12-HETE) and 12(S)-hydroperoxy-eicosatetraenoic
      acid (12(S)-HpETE) did not induce any significant changes in membrane potential.
      CDC inhibited the voltage-gated potassium current and increased the large
      conductance calcium-activated potassium current whereas AA861 inhibited both
      potassium currents. These results confirm that, in the isolated carotid artery of
      the guinea pig, stimulation of endothelial muscarinic receptors involves
      phospholipase C activation and indicate that the activation of phospholipase A2
      and the release of lipoxygenase metabolites is unlikely to explain endothelium
      dependent hyperpolarization.

PMID- 12198334
TI  - N(G)-nitro-L-arginine methyl ester-induced hypertension and natriuretic peptide
      gene expression: inhibition by angiotensin II type 1 receptor antagonism.
AB  - This study examined the role of angiotensin II in the increase of blood pressure,
      activation of cardiac natriuretic peptide gene expression, left ventricular
      hypertrophy, and vascular changes in nitric oxide-deficient hypertension. N(G)
      nitro->L-arginine methyl ester (>L-NAME, 20 mg/kg/d), angiotensin II type 1
      receptor (AT ) antagonist losartan (20 mg/kg/d), or their combination were
      administered orally for 8 weeks in Wistar rats. >L-NAME elevated systolic blood
      pressure, which reached its maximum within 4 weeks (200 +/- 4 mm Hg). Despite
      hypertension, >L-NAME administration for 8 weeks did not induce left ventricular
      hypertrophy. Losartan treatment significantly decreased the development of
      hypertension induced by >L-NAME and decreased left ventricular hypertrophy in
      untreated rats. In contrast, losartan did not prevent the hypertrophic remodeling
      of the mesenteric resistance arteries induced by >L-NAME. >L-NAME treatment
      increased ventricular atrial natriuretic peptide (ANP) and B-type natriuretic
      peptide (BNP) mRNA levels and immunoreactive BNP levels significantly. Losartan
      therapy decreased the >l-NAME-induced ventricular ANP gene expression by 69% (p <
      0.05) and also reduced ventricular BNP mRNA levels so that it did not differ from
      control. Losartan treatment alone decreased ventricular immunoreactive ANP and
      BNP levels by 30% (p < 0.05). These results show that ventricular ANP and BNP
      gene expression are dissociated from the increased ventricular mass in nitric
      oxide deficiency-induced hypertension. Results suggest that >l-NAME-induced
      hypertension and the associated activation of ventricular ANP and BNP gene
      expression are, at least in part, mediated by angiotensin II, whereas the
      resistance vessel hypertrophy following nitric oxide synthase inhibition is
      angiotensin II independent.

PMID- 12198335
TI  - Chronopharmacology of cardiovascular therapy.

PMID- 12198336
TI  - The white-coat effect is associated with increased blood pressure reactivity to
      physical activity.
AB  - OBJECTIVE: The aim of this study was to test the hypothesis that blood pressure
      (BP) reactivity to the stress of a clinic visit, the so-called white-coat effect,
      is associated with increased BP reactivity to physical activity. DESIGN: Patients
      referred to our clinic for assessment of hypertension prospectively underwent 24
      h ambulatory BP monitoring and simultaneous actigraphy. METHODS: The difference
      between mean clinic BP and mean daytime ambulatory BP was considered to be a
      measure of the white-coat effect. Presence or absence of a white-coat effect
      (clinic-daytime difference > 0 mmHg) was added to a mixed model regression of BP
      on mean activity score for the 10-min interval preceding BP measurement. RESULTS:
      The group (n = 421) was heterogeneous in age, gender, mean 24-h BP and use of
      antihypertensive medications. A total of 259 patients had a systolic white-coat
      effect; for diastolic BP there were 264. Female patients exhibited a
      significantly larger white-coat effect. Coefficients for the regressions of both
      systolic and diastolic blood pressure on physical activity levels were
      significantly higher in those who had a white-coat effect. CONCLUSIONS: These
      data suggest increased BP reactivity to activity in those with a white-coat
      effect. Patients with a prominent white-coat effect may experience greater BP
      load during normal daily activities as a consequence of increased BP reactivity.
      In patients with white-coat hypertension, this may contribute to target-organ
      damage.

PMID- 12198337
TI  - Quality control of the blood pressure phenotype in the European Project on Genes
      in Hypertension.
AB  - OBJECTIVES: In the European Project on Genes in Hypertension (EPOGH) standardized
      epidemiological methods were used to determine complex phenotypes consisting of
      blood pressure (BP) in combination with other traits. In this report, we present
      the quality control of one of the BP phenotypes. METHODS: In seven European
      countries eight different research groups recruited random samples of nuclear
      families. Trained observers measured the BP five times consecutively with the
      participants in the seated position at each of two separate home visits, 1 to 3
      weeks apart, according to the guidelines of the British Hypertension Society.
      Quality assurance and quality control of this BP phenotype were implemented
      according to detailed instructions defined in the protocol of the EPOGH study.
      RESULTS: On 31 August 2001, BP measurements of 2476 subjects were available for
      analysis. Fewer BP readings than the five planned per visit occurred in one of
      the eight centres, but only in 0.4% of the home visits. Across centres the
      relative frequency of identical consecutive readings for systolic or diastolic
      blood pressure varied from 0 to 6%. The occurrence of odd readings ranged from 0
      to 0.1%. Of the 49,488 systolic and diastolic BP readings, 24.0% ended on a zero
      (expected 20%). In most EPOGH centres there was a progressive decline in the BP
      from the first to the second home visit. Overall, these decreases averaged 2.36
      mmHg [95% confidence interval (CI): 1.98-2.74, P < 0.001] for systolic BP and
      1.74 mmHg (95% CI: 1.46-2.02, P < 0.001) for diastolic BP. CONCLUSIONS: Quality
      assurance and control should be planned at the design stage of a project
      involving BP measurement and implemented from its very beginnings until the end.
      The procedures of quality assurance set up in the EPOGH study for the BP
      measurements resulted in a well-defined BP phenotype, which was consistent across
      centres.

PMID- 12198338
TI  - The correlation between isolated interventricular septal hypertrophy and 24-h
      ambulatory blood pressure monitoring in apparently healthy air crew.
AB  - BACKGROUND: Interventricular septal (IVS) hypertrophy is considered to affect
      prognosis in hypertensive patients. However, the natural history of isolated
      septal hypertrophy, identified by echocardiography in otherwise healthy subjects
      is not well defined. METHODS: The study population included 51 apparently healthy
      pilots with septal hypertrophy (septal thickness > 11 mm) defined by routine
      echocardiography, with a calculated normal left ventricular (LV) mass. All pilots
      underwent casual blood pressure (BP) measurements and a 24-h ambulatory BP
      monitoring (ABPM). Hypertension (HTN) was defined as a casual measurement of >
      140/90 mmHg. RESULTS: The mean age of the pilots was 38 +/- 11 years and the body
      mass index (BMI) 26.3 kg/m(2). The 17 pilots found to be hypertensive had a
      higher septal thickness than the 34 counterparts with normal BP measurements
      (13.8 +/- 2.0 mm versus 12.6 +/- 1.7 mm, P < 0.04, respectively). The mean
      ambulatory daytime systolic and diastolic BP were higher in comparison to non
      hypertensive pilots (142 +/- 6.2 versus 128 +/- 5.0 mmHg, P < 0.0001 for systolic
      BP and 91 +/- 5.3 versus 78 +/- 4.1 mmHg, P = 0.001 for diastolic BP),
      respectively. The adjusted relative risk (RR) of a subject with an IVS thickness
      P > 12 mm to be hypertensive by ABPM was 3.12 (95% confidence interval 1.04-9.37,
      P < 0.02). CONCLUSIONS: Isolated IVS hypertrophy, even in the presence of normal
      LV mass is associated with HTN. Screening healthy subjects at risk for
      hypertension by echocardiography enables one to identify those who should be
      closely monitored, using among others, ABPM.

PMID- 12198339
TI  - Assessment of repeatability and correlates of arterial compliance.
AB  - OBJECTIVES: The aim of these studies was to assess repeatability of large (C1)
      and small (C2) arterial elasticity indices over various time intervals using the
      HDI/Pulsewave CR-2000 Research CardioVascular Profiling System (Hypertension
      Diagnostics, Inc., Eagan, Minnesota, USA). Non-invasive hemodynamic parameters
      using this device were compared to invasive measurements. METHODS: After a 5-min
      period of rest, 31 healthy hospital employees underwent cardiovascular profiling
      on two occasions within 1 h apart. Another 59 healthy hospital employees
      underwent cardiovascular profiling on two occasions, an average 52 days apart. An
      additional group of 23 patients underwent right and left heart catheterizations
      for routine clinical indications and hemodynamic assessment was performed
      invasively and non-invasively. RESULTS: For short-term repeatability, the mean
      difference of C1 was +0.25 +/- 2.83 ml/mmHg x 10 (P = NS) and C2 was -0.14 +/-
      1.86 ml/mmHg x 100 (P = NS). For intermediate test repeatability, the mean
      difference of C1 was -0.415 +/- 2.97 ml/mmHg x 10 (P = NS) and C2 was -0.19 +/-
      2.67 ml/mmHg x 100 (P = NS). In the invasive protocol, both aortic diastolic
      blood pressure (-4.74 +/- 9.7 mmHg) and systemic vascular resistance (-194 +/-
      264 dyne x s x cm(-5)) were significantly lower invasively. CONCLUSIONS:
      Measurements with the HDI/Pulsewave CR-2000 Research CardioVascular Profiling
      System are repeatable over both a short and intermediate period of observation.
      Furthermore, non-invasive hemodynamic parameters reasonably agree with invasive
      measurements.

PMID- 12198340
TI  - Validation of the Omron HEM-907 device for blood pressure measurement.
AB  - BACKGROUND: The aim of this study was to validate the Omron HEM-907 blood
      pressure (BP) measuring device according to the international validation
      protocol. DESIGN: The international validation protocol is divided into two
      phases: the first phase is performed on 15 selected subjects and if the device
      passes this phase, 18 more subjects are selected making a total number of 33
      subjects on which the final validation is performed. METHODS: For each subject,
      BP measurements were performed simultaneously by two trained observers using
      mercury sphygmomanometers alternately with the Omron HEM-907 device. In all, 99
      measurements were obtained for comparison. The difference between the BP value
      given by the device and that obtained by the two observers (mean of the two
      observers) was calculated for each measure. RESULTS: The difference between the
      two observers was -1 +/- 2 mmHg for the systolic BP (SBP) and for the diastolic
      BP (DBP). The Omron HEM-907 passed the first phase of the validation process. For
      the second phase, the average differences between the device and mercury
      sphygmomanometer readings were -1 +/- 7 and -5 +/- 6 mmHg for SBP and DBP
      respectively. Readings for the HEM-907 device differed by less than 5 mmHg for 61
      of the systolic readings and 52 of the diastolic readings; by less than 10 mmHg
      for 85 of the systolic readings and 85 of the diastolic readings; and by less
      than 15 mmHg for 94 of the systolic readings and 96 of the diastolic readings.
      CONCLUSIONS: The Omron HEM-907 device passes the two phases of the international
      validation protocol.

PMID- 12198341
TI  - Validation of the A&D UA-631 (UA-779 Life Source) device for self-measurement of
      blood pressure and relationship between its performance and large artery
      compliance.
AB  - OBJECTIVES: To determine the accuracy of the UA-631 (UA-779 Life Source for the
      American market) blood pressure monitor developed by the A&D Company (Toshimi-ku,
      Tokyo, Japan). DESIGN: Device evaluation was performed using a new protocol
      proposed by the Working Group on blood pressure monitoring of the European
      Society of Hypertension (ESH). Monitor performance was assessed in relation to
      subjects' gender, age, skinfold thickness, arm circumference, BMI, and elasticity
      index of large (C1) and small (C2) arteries. METHODS: The A&D recorder was
      assessed according to the various phases of the protocol. Sequential readings
      were taken for the main validation test. Outcome was classified according to the
      criteria of ESH recommendations, which are based on four zones of accuracy
      differing from the mercury standard by 5, 10, 15 mmHg, or more. RESULTS: The main
      validation test was performed in 66 subjects for a total of 198 device
      measurements. The A&D monitor passed all three phases both for systolic and
      diastolic blood pressure (SBP and DBP). Mean blood pressure difference between
      device and observers was 2 +/- 5 mmHg for SBP and 1 +/- 3 mmHg for DBP. The
      absolute discrepancy between device and observers (4 +/- 4 mmHg for SBP, and 2 +/
      2 mmHg for DBP) was related to age (negatively) and to C1 (positively), but in a
      multivariable regression analysis only C1 remained a significant independent
      predictor of the absolute device-observer discrepancy. CONCLUSIONS: These data
      show that the A&D UA-631 device satisfies the new recommended ESH accuracy levels
      for both SBP and DBP. Its performance seems to be better in subjects with stiffer
      arteries.

PMID- 12198342
TI  - World Trade Center disaster effect on blood pressure.

PMID- 12198343
TI  - Backspatter on the firearm and hand in experimental close-range gunshots to the
      head.
AB  - The deposition of backspatter on the firearm or person shooting can greatly
      assist the reconstruction of shooting incidents. Backspatter was investigated in
      experimental transverse gunshots (9-mm Luger) to the heads of calves (n = 9) from
      shooting distances of 0 to 10 cm. The firearms were examined with a magnifying
      glass; the surgical gloves and the right sleeve worn by the person shooting were
      examined with a stereomicroscope. On the firearms, backspatter of blood was found
      in five of the nine cases, and one or both gloves showed bloodspatter deposits in
      six and the right sleeves in four cases. Most droplets were 1 to 3 mm and
      circular or elongated. In addition, a fine spray of tiny blood deposits was
      present on the firearm and textiles in four cases. The distribution of the
      droplets on the firearms varied: the areas included regions shielded by prominent
      parts, and the droplets were predominantly located on the extensor side of the
      fingers and the radial aspect of the hands and sleeves. Backspatter of tiny bone
      fragments was recovered from the firearm and sleeve in only one case, but tissue
      (bone, fat, muscle, skin) was present on the ground in front of the entrance
      wound in seven cases. A careful investigation, including appropriate lightning
      and magnification, is necessary for reliable statements concerning the absence of
      backspatter or the extent of backspatter present.

PMID- 12198344
TI  - The seromuscular tear and other intestinal lesions in the seatbelt syndrome: a
      clinical and pathologic study of 29 cases.
AB  - The authors describe the clinical and pathologic findings in 29 patients with
      injuries from motor vehicle accidents. The seromuscular tear (SMT), the hallmark
      intestinal injury of the seatbelt syndrome, is an unambiguous lesion similar in
      all segments of bowel and is caused by a tear that separates the inner muscularis
      from the submucosa. It is characterized by (1) a wedge that strips the submucosa
      from the inner circular muscle; (2) a bending retraction of the torn muscularis
      toward the uninvolved bowel wall; (3) mucosal-submucosal fold effacement, causing
      the mucosa-submucosa bridge spanning the tear to become paper thin; and (4) the
      vulnerability of this bridge to ischemia that in 35% of the tears studied
      culminated in incipient or frank perforations and/or gangrene. Large SMTs,
      particularly the circumferential degloving type, are most prone to develop these
      complications. These findings militate against the idea that the SMT is a trivial
      lesion. The SMT occurred in 90% of patients in this report and accounted for 65%
      of all intestinal lesions. Seventy-three percent of the tears developed in the
      colon, and one third of all SMTs occurred in the sigmoid colon. Two thirds of all
      intestinal and mesenteric injuries clustered in three sites: the ileocecal
      region, the sigmoid colon, and the jejunum. Perforations were the principal
      lesion in the jejunum and SMTs at the other two locations. Ninety percent of
      patients experienced two or more intestinal lesions. This suggests the
      simultaneous action of different traumatic mechanisms on the bowel and its
      mesenteries in seatbelted persons who are in motor vehicle accidents.

PMID- 12198345
TI  - High-speed documented experimental gunshot to a skull-brain model and radiologic
      virtual autopsy.
AB  - The authors documented and evaluated experimental gunshots to a skull-brain model
      with high-speed photography and subsequent radiographic examination for
      comparison of the morphologic findings in the model. The artificial skull was a
      polyurethane ball constructed in layers, with a porous diploe sandwiched between
      a tabula externa and a tabula interna. The brain itself was simulated with
      gelatin 10% at 4 degrees C, a material well known in wound ballistics. Gunshots
      were fired at the model from a distance of 10 m and documented with high-speed
      photography (up to 50 million frames/sec). Subsequently, a complete examination
      of the artificial skull was performed, including spiral computed tomography (with
      two-dimensional and three-dimensional reconstructions) and classic skull autopsy.
      The high-speed photographs clearly showed the dynamic development of the skull
      fracture system from an external perspective. The subsequent radiographic
      examination of the entire head volume created two-dimensional reformations in any
      plane and three-dimensional reconstructions of the gunshot injury of the
      polyurethane skull-brain model, especially the wound channel and the fracture
      system. Thanks to the model and high-speed photographs, the dynamic development
      of the morphology of a gunshot wound could be documented and studied. The data
      from computed tomography, using two-dimensional and three-dimensional
      postprocessing with a perspective view, were very similar to those from classic
      head autopsy, but derived in a hands-off and nondestructive manner. This
      examination method leads the way to radiographic digital autopsy or virtual
      autopsy.

PMID- 12198346
TI  - Open revolver cylinder at the suicide death scene.
AB  - Revolvers with an open cylinder were found at three death scenes of apparently
      self-inflicted gunshot wounds. All three handguns were Smith & Wesson.38 or.357
      revolvers. Investigation revealed that firing the gun with the thumb on the
      cylinder release latch could disengage the cylinder. A combination of gravity and
      recoil impact against the thumb would open the cylinder and even allow the casing
      and the unspent cartridges to fall from the gun, creating a confusing death
      scene.

PMID- 12198347
TI  - Asphyxial suicide with helium and a plastic bag.
AB  - Suicide by helium inhalation inside a plastic bag has recently been publicized by
      right-to-die proponents in "how to" print and videotape materials. This article
      reports a suicide performed according to this new and highly lethal technique,
      which is also a potentially undetectable cause of death. Toxicology information
      could not determine helium inhalation, and drug screening did not reveal data of
      significance. The cause of death could be determined only by the physical
      evidence at the scene of death. Helium inhalation can easily be concealed when
      interested parties remove or alter evidence. To ensure that their deaths are not
      documented as suicide, some individuals considering assisted suicide may choose
      helium methods and assistance from helpers. Recent challenges to Oregon's
      physician-assisted suicide law may increase interest in helium instead of
      barbiturates for assisted suicide.

PMID- 12198348
TI  - Diagnostic problems associated with cadaveric trauma from animal activity.
AB  - Analysis of a series of deaths between 1986 and 2001 resulting from natural
      disease, accidents, suicides, and homicide, where postmortem animal activity had
      traumatized bodies, was undertaken at the Forensic Science Center in Adelaide to
      demonstrate the range of lesions that may occur and problems in interpretation
      that result. Tissue damage had been caused by a variety of animals, including fly
      larvae, ants, birds, dogs, rodents, sea lice, and sharks. Postmortem animal
      activity had disguised injuries, modified wounds, and created the appearances of
      inflicted injury. Problems with identification occurred after postmortem facial
      trauma, and loss of organ parenchyma had interfered with, or precluded, the
      precise determination of the manner of death in some cases. Specific kinds of
      tissue and organ damage may occur after death, necessitating careful assessment
      of lesions in a search for characteristic features of animal activity. The
      pattern of lesions may enable identification of the particular species of animal
      involved.

PMID- 12198349
TI  - Recovery of a mummified pregnant woman from a 55-gallon drum more than 30 years
      after her death.
AB  - The body of a 28-year-old near-term pregnant woman was found in a 55-gallon steel
      drum in a crawl space under a house more than 30 years after her disappearance
      and death. At autopsy the body was remarkably well preserved and mummified, as
      was that of a male fetus. The decedent had 10 scalp lacerations and multiple
      comminuted depressed skull fractures and had died as a result of blunt force head
      trauma.

PMID- 12198350
TI  - Murder-suicide in New Hampshire, 1995-2000.
AB  - Combined murder-suicide is defined as homicide(s) followed by the perpetrator's
      suicide within 1 week of the homicide(s). This phenomenon is observed worldwide
      with generally similar incidence rates. The authors report data from New
      Hampshire, a population distinguished from those in previous United States
      studies by its location, racial homogeneity, nonurban character, and low homicide
      rate. Sixteen murder-suicide events occurred in New Hampshire between October
      1995 and October 2000. This represents an incidence of 0.26 per 100000 person
      years, a rate similar to previously reported values. Murder-suicide events
      accounted for 14.7% of all homicides in the state, higher than previous studies
      but not unexpected in view of the state's lower homicide rate. Most perpetrators
      were male (94%), and most victims were female (88%), often in a spousal or
      consortial relationship. Firearms accounted for the majority of deaths. Various
      cofactors are examined, and a comparison of two recently proposed classification
      systems is discussed.

PMID- 12198351
TI  - Estimation of body exposure to explosion.
AB  - An ordnance-disposal expert was killed while disposing of a cache of explosives.
      The likely position of the body was reconstructed by modeling the explosion as an
      omnidirectional emission of particles from a model of the explosion site and
      noting the distribution of particles on a model of a human. The applications and
      limitations of this method in reconstructing the events and correlation with the
      injuries noted at autopsy are discussed.

PMID- 12198352
TI  - Pulmonary embolism: a rare cause of sudden infant death.
AB  - Pulmonary embolism can be observed at any age, but it occurs very rarely in the
      infant. The authors report the case of a 12-month-old boy who suddenly died
      during clinical improvement of gastroenteritis associated with otitis. Autopsy
      showed signs of dehydration and acute left pulmonary embolism, which was the
      cause of death. Thrombosis of the inferior vena cava extending into renal veins
      was seen. In this case, plasma hyperosmolality caused by dehydration might have
      favored the formation of venous thromboses. The various risk factors of pulmonary
      embolism in the child are discussed, including genetic factors.

PMID- 12198353
TI  - Self-strangulation: an uncommon but not unprecedented suicide method.
AB  - The authors report two cases of self-strangulation in which the investigators had
      initially suspected homicide but eventually deemed the cases to be suicide. Self
      strangulation may be mistaken for homicide because it is widely believed to be
      impossible to carry out this act without assistance. An accurate medicolegal
      evaluation of the circumstances, a thorough postmortem examination, and
      methodical inspection of the site are extremely important in such cases. It is
      equally important to examine the knot or other means used to exert pressure on
      the neck and to document its position. Finally, to gain a full understanding of
      these unusual cases, close collaboration between the two different fields,
      investigative and medicolegal, is essential.

PMID- 12198354
TI  - Immunohistochemical study of basic fibroblast growth factor and vascular
      endothelial growth factor expression for age determination of cutaneous wounds.
AB  - The authors investigated the expression of basic fibroblast growth factor (bFGF)
      and vascular endothelial growth factor (VEGF) during skin wound healing using
      immunohistochemical techniques. After a full-thickness incision was made on the
      dorsal skin, mice were killed 0.5, 1, 3, 8, 24, 72, 144, or 240 hours after
      incision, and the wound was excised. To evaluate the influences of postmortem
      degeneration, cutaneous wound excision was performed 1 to 5 days after the mice
      were killed. The excised wounds were stained by the conventional streptoavidin
      biotinylated peroxidase complex method, using specific antibodies, and the ratio
      of the number of positive cells to total cells was determined. Expression of bFGF
      was detected in the nuclei of epidermal cells and fibroblasts in the early 0.5-
      to 1-hour phases and the late 24- to 144-hour phases. Expression of VEGF was
      detected in the cytoplasm of epidermal cells in the 24- to 144-hour phases.
      Immunoreactivity of both cytokines was detected 1 day post mortem and was
      especially well preserved in the fibroblasts. Time-dependent expression of both
      factors suggested that they would be useful markers for the determination of
      wound age. However, bFGF should be superior to VEGF because of its earlier
      expression and because of its more persistent expression in dermal fibroblasts
      with increasing postmortem interval.

PMID- 12198355
TI  - Chelating resin-based extraction of DNA from dental pulp and sex determination
      from incinerated teeth with Y-chromosomal alphoid repeat and short tandem
      repeats.
AB  - A procedure utilizing Chelex 100, chelating resin, was adapted to extract DNA
      from dental pulp. The procedure was simple and rapid, involved no organic
      solvents, and did not require multiple tube transfers. The extraction of DNA from
      dental pulp using this method was as efficient, or more so, than using proteinase
      K and phenol-chloroform extraction. In this study, the Chelex method was used
      with amplification and typing at Y-chromosomal loci to determine the effects of
      temperature on the sex determination of the teeth. The extracted teeth were
      incinerated in a dental furnace for 2 minutes at 100 degrees C, 200 degrees C,
      300 degrees C, 400 degrees C, and 500 degrees C. After the isolation of DNA from
      the dental pulp by the Chelex method, alphoid repeats, and short tandem repeats,
      the human Y chromosome (DYZ3), DYS19, SYS389, DYS390, and DYS393 could be
      amplified and typed in all samples incinerated at up to 300 degrees C for 2
      minutes. The DYS389 locus in some samples could not be amplified at 300 degrees C
      for 2 minutes. An autopsy case is described in which genotypings of DYS19,
      DYS390, and DYS393 from dental pulp obtained from a burned body were needed. The
      data presented in this report suggest that Chelex 100-based DNA extraction,
      amplification, and typing are possible in burned teeth in forensic autopsy cases.

PMID- 12198356
TI  - Personal identification from human remains by mitochondrial DNA sequencing.
AB  - The authors report four cases in which severely damaged human remains were
      identified by mitochondrial DNA (mtDNA) sequencing. Degraded DNA was extracted
      from highly adipoceratous tissues using the phenol-chloroform method and
      polymerase chain reaction amplified for sequencing of two hypervariable regions,
      hypervariable region 1 and hypervariable region 2, of mitochondrial DNA. They
      also sequenced these regions of blood samples that were obtained from the
      presumptive mother or sister of the human remains. The sequencing results were
      compared with each other and with the Anderson's sequence. It was concluded from
      the sequence data that a lower part of a body in case 1 and some organs in case 2
      were from the same woman, and a human head in case 3 and a female body in case 4
      were from the relative of a presumptive mother and a sister, respectively.

PMID- 12198357
TI  - Penetration of a piece of World War II rifle grenade initially suspected as a
      stab wound.
AB  - The authors report the case of a 58-year-old man found dead by his son in the
      forest where he had gone to cut wood for winter. Initial examination showed an
      upper left laterocervical wound compatible with a stab wound. Radiography and
      autopsy performed the next day showed a piece of metal located in the left part
      of the occipital bone, associated with a half-ring fracture of the occipital bone
      and consequent diffuse subarachnoid hemorrhage. Death was attributed to a spinal
      shock after impact at the cervicocephalic junction. Investigators returned to the
      scene and found a few more metal elements and also a 20-cm deep and 40-cm wide
      crater underneath a fire the deceased had set. Army experts concluded that the
      metal pieces belonged to an ATM 9 antitank rifle grenade used by the U.S. Army
      during World War II. Death was considered accidental, the deceased having
      unfortunately set a fire over the grenade.

PMID- 12198358
TI  - Fatal splenic arterial aneurysmal rupture associated with chronic pancreatitis.
AB  - Splenic arterial aneurysms (SAA) are rare and are usually atherosclerotic and/or
      related to pregnancy. Because pregnancy is the most important predisposing
      factor, the strong predilection of SAA for women is not surprising. The authors
      report a case of SAA rupture in a man with chronic pancreatitis as the
      predisposing factor. A 56-year-old man with abdominal pain and hematemesis was
      resuscitated and underwent endoscopy, but he died 18 hours later of massive
      hematemesis before definitive surgery could be carried out. At autopsy, there was
      chronic pancreatitis with fibrous adhesions tethering the tail of the pancreas,
      spleen, and posterior wall of the stomach together. The SAA was indented into the
      posterior wall of the stomach, into which it had ruptured from without. He also
      had alcoholic cirrhosis but no esophageal varices or conventional gastric ulcers.
      Other important predisposing factors such as abdominal trauma, infective
      endocarditis, polyarteritis nodosa, and segmental medial arteriopathy were
      absent. Histologic examination confirmed the rupture of the SAA. The SAA had
      Monckeberg medial calcinosis but little evidence of atherosclerosis. The well
      documented complications of acute and chronic pancreatitis include shock,
      abscess, pseudocyst formation, and duodenal obstruction. This report describes
      the rare complication of SAA rupture, which may be fatal.

PMID- 12198359
TI  - Determination of sex from the clavicle and scapula in a Guatemalan contemporary
      rural indigenous population.
AB  - The clavicle has been described as a useful bone for the metric determination of
      sex of human skeletal remains in a contemporary, predominantly white, North
      American forensic sample. In this article, measurements of clavicle and scapula
      are provided for a contemporary Guatemalan rural indigenous sample of forensic
      origin. Maximum length and circumference at midshaft of the clavicle, and height
      and width of the glenoid fossa of the scapula, were measured in 35 female and 62
      male clavicles, and in 38 female and 65 male scapulae. Discriminant function
      analysis was used to study sexual dimorphism in this population with a
      classification purpose. Leave-one-out method (jackknife) matrices produced
      classification success rates ranging from 85.6% to 94.8%. A comparison with the
      North American forensic sample showed low percentages of correctly sexed
      Guatemalan male clavicles, ranging from 29.4% to 54.9%. The choice of an
      appropriate standard for the metric determination of sex is a crucial step in
      forensic anthropology.

PMID- 12198360
TI  - Sudden death in an infant resulting from torsion of the uterine adnexa.
AB  - A 2-month-old infant girl died suddenly as a result of torsion of the uterine
      adnexa. The infant was found unresponsive in bed and was pronounced dead shortly
      after her arrival at a hospital. There were no antecedent signs of illness. At
      autopsy, the right ovary and right fallopian tube were twisted and were dark
      purple, swollen, and necrotic. The right ovary was enlarged by a follicle cyst 4
      cm in diameter, which likely precipitated the torsion. The mechanism of death was
      unclear but may have resulted from the release of cytokines produced in response
      to necrotic adnexal tissue. Fatal uterine adnexal torsion has been reported
      rarely in infants; in all those cases there were antecedent symptoms. Torsion of
      the uterine adnexa should be included in the differential diagnosis of sudden
      death in infancy.

PMID- 12198361
TI  - Coma blisters in a case of fatal theophylline intoxication.
AB  - A case of fatal poisoning caused by theophylline toxicity (serum level 127 micro
      g/ml) is presented. At external examination, skin blisters on regions exposed to
      pressure were distinctive. Histologic examination demonstrated subepidermal
      bullae with eosinophilic necrosis of the eccrine sweat gland coil but no
      epidermal necrosis, vascular changes, or inflammatory infiltrate. To the authors'
      knowledge, this is the first description of coma blisters in a case of
      theophylline intoxication.

PMID- 12198362
TI  - Suicide by self-immolation in Durban, South Africa: a five-year retrospective
      review.
AB  - Self-immolation is an uncommon method of suicide, and its occurrence in South
      Africa is thus far unknown. This study aimed to determine the prevalence of self
      immolation deaths and to establish a profile of these cases and the circumstances
      under which this condition occurs. A 5-year (1996-2000) retrospective review at a
      mortuary in Durban, South Africa, was conducted. Data were obtained from the
      Department of Forensic Medicine, the Medical Research Council's National Injury
      Mortality Surveillance System, and police and hospital records. During the study
      period, there were 12339 nonnatural deaths, of which 696 (5.6%) were suicides.
      Self-immolation accounted for 69 (0.6%) of all nonnatural deaths and 69 (9.9%) of
      all suicides. The subjects had a mean age of 31.2 years and were predominantly
      female (76.8%) and black (81.2%). The mean burn surface area was 63.3%, and the
      mean injury severity score was 36.9. Accelerant use was documented in 53 (76.8%)
      of cases, and paraffin was preferred. All cases occurred indoors. The proportion
      of suicides due to self-immolation in our study is excessive when compared with
      international studies that report figures between 0.9% and 2.2% of suicides.
      Additional studies are necessary to further elucidate the reasons for this
      discrepancy.

PMID- 12198363
TI  - A review of methadone deaths in Jefferson County, Alabama.
AB  - Interpretation of the concentration of a drug is more difficult when a
      combination of drugs is present in a decedent's blood. An increase in deaths
      resulting from co-intoxication with methadone and a benzodiazepine led the
      authors to perform a retrospective study of cases examined at the Jefferson
      County Coroner/Medical Examiner Office. They found 101 deaths wherein methadone
      was detected in the blood. Based on the drugs detected in the blood, these 101
      cases were grouped into four categories: (1) pure methadone intoxication, (2)
      intoxication with methadone and benzodiazepine, (3) intoxication with methadone
      and other drugs excluding benzodiazepine, and (4) intoxication with methadone,
      benzodiazepines, and other drugs. Methadone was the sole intoxicant in 15 cases,
      with a mean concentration of 0.27 mg/L. Benzodiazepines were the most frequently
      detected co-intoxicant (60 of 101 cases). Benzodiazepine was the only co
      intoxicant in 30 cases, and the mean methadone concentration in those 30 cases
      was 0.599 mg/L. Higher levels of methadone may occur in acute intoxication with
      methadone and benzodiazepine because benzodiazepines compete with methadone for
      methadone receptors. Higher levels of methadone may occur with chronic abuse of
      methadone and benzodiazepines because over time, benzodiazepines inhibit the
      hepatic enzymes that metabolize methadone.

PMID- 12198364
TI  - Cerivastatin and gemfibrozil-induced cardiac rhabdomyolysis.

PMID- 12198367
TI  - Role of endotoxin in NF-kappaB activation by ethanol in rat hepatocytes.
AB  - BACKGROUND: Endotoxin plays an important role in the progression of alcoholic
      liver injury. However, the role of endotoxin in acute activation of NF-kappaB by
      ethanol remains unclear. METHODS: In primary rat hepatocyte cultures treated with
      ethanol and/or endotoxin, the DNA-binding activity of NF-kappaB in the nuclear
      extract was estimated by electrophoretic mobility shift assay. After pretreatment
      of a CYP2E1 inhibitor, 4-methyl pyrazole or diallyl sulfide, NF-kappaB activity
      was also measured in the same manner. RESULTS: Ethanol or endotoxin caused
      activation of NF-kappaB in primary rat hepatocytes. Taking 50 mM of ethanol and
      endotoxin together raised the rapid increase in NF-kappaB activation, but both
      100 mM of ethanol and endotoxin treatment reduced the increase. Addition of
      diallyl sulfide decreased the activity at rapid phase but increased it after 60
      min, whereas addition of 4-methyl pyrazole caused no change of the activity at
      rapid phase but raised it after 60 min. Pretreatment with both endotoxin and a
      CYP2E1 inhibitor raised the activation of NF-kappaB constantly after ethanol
      addition. These findings suggest that endotoxin plays a critical role in the
      metabolism-independent activation of NF-kappaB by ethanol. CONCLUSIONS: Endotoxin
      raised metabolism-independent activation of NF-kappaB by high ethanol in rat
      hepatocytes.

PMID- 12198366
TI  - Investigation of quantitative trait loci in the CCKAR gene with susceptibility to
      alcoholism.
AB  - BACKGROUND: Cholecystokinin (CCK) plays an important role in the function of the
      central nervous system by interacting with dopamine and other neurotransmitters.
      We previously reported genetic variations in the promoter and coding regions of
      the CCKA receptor (CCKAR), CCKBR, and CCK genes and a possible association
      between polymorphisms of the CCKAR gene and alcoholism. In this study,
      association analyses were re-examined between the polymorphisms of the promoter
      region of the CCKAR gene and patients with alcohol withdrawal symptoms, in
      addition to patients with alcoholic liver injury. METHODS: A total of 131
      Japanese male patients with alcohol withdrawal symptoms, 70 Japanese patients
      with alcoholic liver injury, and 98 age-matched Japanese male controls
      (nonhabitual drinkers) were examined using polymerase chain reaction-based single
      strand conformational polymorphism and sequencing analyses. RESULTS: Significant
      differences between patients with hallucination and controls were found in the
      allele frequencies at the -388 and -85 loci of the CCKAR gene (p = 0.0095, p =
      0.0087, respectively), but these differences were not significant after
      Bonferroni correction for multiple testing. In contrast, the frequency of the
      homozygous genotype -85CC was significantly higher in hallucination-positive
      patients than in controls (p = 0.0031) and in patients with hallucination
      accompanying delirium tremens than in controls (p = 0.0022), and these
      differences were significant after Bonferroni correction. CONCLUSIONS: The data
      from the case control suggest that polymorphisms of the promoter region of the
      CCKAR gene do not play a major role in the pathogenesis of alcohol withdrawal
      symptoms or alcoholic liver injury. However, a significant association was found
      between polymorphism at the -85 locus of the CCKAR gene and patients with
      hallucination, and especially patients with hallucination accompanying delirium
      tremens.

PMID- 12198368
TI  - Assessment of a difference in ALDH2 heterozygotes and alcoholic liver injury.
AB  - We have speculated that the degree of liver dysfunction in alcoholic liver
      disease with ALDH2*1/2*2 may be less pronounced than that with ALDH2*1/2*1. In
      the present study, outpatients with alcoholic liver injury were examined for
      ALDH2 genotype and biochemical data. The number of patients was 29 cases of
      nonspecific changes, 16 cases of fatty liver, 5 cases of liver fibrosis, and 44
      cases of liver cirrhosis. Biochemical data were evaluated with ALDH2
      heterozygotes data obtained by PCR-SSCP. The ALDH2*1/2*1 and ALDH2*1/2*1
      genotypes accounted for 90% and 10%, respectively. As for ALDH2*1/2*2, there were
      three patients with nonspecific changes, three with fatty liver, one with liver
      fibrosis, and two with liver cirrhosis. In alcoholic liver disease patients, when
      the ALDH2*1/2*2 genotype was compared with the ALDH2*1/2*1 genotype with
      biochemical data, the gamma-GTP value in patients with ALDH2*1/2*2 was
      significantly higher than with ALDH2*1/2*1 ( < 0.005). When the frequency of
      ALDH2 genotype was determined in patients with alcoholic liver injury, ALDH2
      heterozygotes accounted for 15% for the non-cirrhosis group, and 5% for the
      cirrhotic group. When a relationship between the amount of ethanol intake and
      biochemical data were determined in patients with alcoholic liver injury who have
      ALDH2 heterozygotes, the glutamic oxaloacetic transaminase (GOT) and gamma-GTP
      values were significantly higher at an ethanol intake amount of ethanol more than
      100 g per day than intake less than 100 g per day ( < 0.05). The alcoholic
      patients with ALDH2*1/2*2 drink a slight amount of ethanol, the liver injury is
      found to be stronger than those with ALDH2*1/2*1 when they drink more than 100 g
      ethanol per day.

PMID- 12198369
TI  - Tandem repeat polymorphism of the CYP2E1 gene: an association study with
      esophageal cancer and lung cancer.
AB  - BACKGROUND: Cytochrome P-450 (CYP) enzymes have been shown to play important
      roles in chemical carcinogenesis. Reports have indicated that polymorphism in
      CYP1A1, CYP1A2, CYP2A6, CYP2E1, and CYP2D6 are associated with an altered risk of
      developing cancers of the lung, bladder, liver, and colon. CYP2E1 plays an
      important role in alcohol metabolism and participates in the metabolic activation
      of various carcinogens, such as N-nitrosodimethylamine. Recently, we found
      repeated sequences that consist of four alleles (A1, A2, A3, and A4) and six
      genotypes (A1/A2, A2/A2, A2/A3, A2/A4, A3/A4 and A4/A4) of the CYP2E1 gene. In
      the present study, we investigated whether these polymorphisms are associated
      with lung cancer and esophageal cancer. METHODS: DNA was isolated from blood
      samples of 192 healthy control subjects, 85 patients with lung cancer, and 82
      patients with esophageal cancer in Japanese males. DNA samples were amplified by
      polymerase chain reaction in the 5'-flanking region of the CYP2E1 gene and in
      exon 12 in the ALDH2 gene. The tandem repeat polymorphisms were examined using
      DNA fragment analysis. Missense mutations in exon 12 of the ALDH2 gene were
      examined using fluorescence-based single strand conformational change
      polymorphism analysis. Written informed consent was obtained from all the
      subjects. RESULTS: In the CYP2E1 gene 5'-flanking region polymorphism, patients
      with esophageal cancer showed significantly higher frequency of the A4/A4
      genotype compared with the control subjects (p = 0.02), but no difference was
      found in patients with lung cancer. The frequencies of the mutant ALDH2*2 allele
      were significantly higher in patients with esophageal cancer (27.7%) than in
      healthy control subjects (7.3%; p< 0.0001; habitual alcohol drinkers).
      CONCLUSIONS: The distribution of genotypes and allele frequencies of the tandem
      repeats of the 5'-flanking region of the CYP2E1 gene was significantly different
      in patients with esophageal cancer.

PMID- 12198371
TI  - Up-regulation of transferrin receptor expression in hepatocytes by habitual
      alcohol drinking is implicated in hepatic iron overload in alcoholic liver
      disease.
AB  - BACKGROUND: Hepatic iron overload is often seen in alcoholic liver disease (ALD).
      We previously reported that the expression of 4-hydroxy-2-nonenal-protein
      adducts, which is a lipid peroxidative product and can be used as a marker of
      radical-mediated cellular damage, was increased in iron-overloaded hepatocytes
      with ALD. However, the mechanism of hepatic iron overload in ALD has not been
      clarified. In this study, to elucidate the mechanism of hepatic iron overload in
      ALD, we immunohistochemically investigated the expression of transferrin receptor
      (TfR), which mainly acts for cellular iron uptake. METHODS: Hepatic tissues were
      obtained from 31 patients with ALD and 5 normal livers by percutaneous needle
      biopsy under laparoscopy or ultrasound guidance. Chemical detection of hepatic
      iron accumulation was performed by Perls' Prussian blue stain.
      Immunohistochemical detection of TfR expression was done using human monoclonal
      anti-TfR antibody (TR104) according to the avidin-biotin complex method with
      alkaline phosphatase. RESULTS: Excess iron accumulation was found in 22 hepatic
      tissues with ALD but not in any normal hepatic tissues. TfR expression was
      increased in hepatocytes of 18 hepatic tissues with ALD but was not detected in
      any normal hepatic tissues. The mean duration of abstinence of patients who
      demonstrated positive TfR expression in hepatocytes was significantly shorter
      than that of patients who demonstrated negative TfR expression (positive: 14
      days; negative: 30 days). However, total ethanol consumption, daily ethanol
      intake, and serum aspartate aminotransferase and gamma-glutamyl transpeptidase
      values on admission were not significantly correlated with TfR expression in
      hepatocytes. CONCLUSIONS: The up-regulation of TfR expression in hepatocytes is
      implicated in hepatic iron overload in ALD, and habitual alcohol drinking is an
      important factor for the induction of TfR expression.

PMID- 12198370
TI  - Influence of moderate drinking on purine and carbohydrate metabolism.
AB  - BACKGROUND: We examined the influences of a moderate intake level of three types
      of alcoholic beverages--beer, whisky, and Shochu (Japanese distilled liquor)--on
      purine and carbohydrate metabolism and excretion in healthy male volunteers,
      concerning (1) the extent of contribution of purine bodies contained in beer to
      uric acid metabolism and (2) a comparison between two types of distilled spirits
      with (whisky) and without (Shochu) aging in oak wood barrel storage. METHODS:
      Three sets of studies were conducted in which 10 to 13 healthy adult men were
      instructed to drink three types of alcoholic beverages at a slightly higher level
      (0.8 ml of ethanol equivalent/kg body weight) than moderate drinking
      (approximately 30.4 ml or less for men). A low purine beer was test-manufactured
      by treating nucleosides that were contained in wort and remained in beer with
      purine nucleoside phosphorylase derived from Ochrobacterium anthropi, thereby
      converting them into corresponding purine bases that were easily assimilated by
      beer yeast. RESULTS: Although beer intake enhanced the level of serum uric acid
      by 13.6%, blood glucose by 26.7%, and insulin level by 5.1-fold, drinking a
      moderate level of distilled liquor (whisky, Shochu) did not increase the serum
      uric acid level or the other two parameters. The serum uric acid level observed
      after drinking beer with a purine body concentration reduced by 28% (68% in
      nucleosides and purine bases) was almost identical to the level observed after
      drinking regular beer. Whisky has been found to have a property that decreases
      the serum uric acid level. Excretion of uric acid from blood is increased by 27%
      after drinking whisky. CONCLUSIONS: Moderate drinking of distilled liquors did
      not enhance serum uric acid level, blood glucose, or insulin level in healthy
      male subjects. Increased serum uric acid after beer intake could not be explained
      mostly with their purine body congeners. Whisky showed the eliminative property
      in serum uric acid through excretion of it from blood to urine. At a moderate
      drinking level, beer and whisky have different effects on purine metabolism or
      excretion.

PMID- 12198372
TI  - Acetaldehyde-induced growth retardation and micro-heterogeneity of the sugar
      chain in transferrin synthesized by HepG2 cells.
AB  - BACKGROUND: A carbohydrate-deficient transferrin (CDT) is the most useful marker
      of alcohol abuse; however, the mechanism of production and the pathophysiologic
      roles of CDT remain obscure. The effects of alcohol and its metabolites on growth
      and proliferation, transferrin synthesis, and phosphomannomutase enzyme activity
      in a human hepatoblastoma, HepG2, were examined. METHODS: HepG2 cells were
      treated with either ethanol at 80 mM or acetaldehyde at 400 microM. Transferrin
      secreted by the cells was prepared from conditioned culture medium by single-step
      immunoaffinity column chromatography using a goat-specific antibody against human
      transferrin. Phosphomannomutase and some related enzyme activities in the cell
      extracts were determined. Reverse transcription-polymerase chain reaction
      analysis of phosphomannomutase mRNA expression was also determined in HepG2
      cultured with or without acetaldehyde (400 microM). RESULTS: HepG2 cells usually
      synthesized and secreted transferrin with three separated bands: main broad bands
      estimated to be 78 to 82 kDa, 75 kDa, and 72 kDa. The last two bands were
      compatible with part or the entire N-glycans-deficient transferrin (CDT) from
      alcoholic liver damage. Increased secretion of CDT from HepG2 correlated well
      with the extent of growth retardation to the level of confluent cell density. The
      activity of phosphomannomutase also decreased with prolongation of cellular
      doubling time. Furthermore, acetaldehyde treatment at 400 microM accelerated the
      inhibitory effect of cell growth compared with nontreated cells, and this
      condition facilitated CDT secretion from HepG2 cells. Determination of the enzyme
      activity and mRNA expression indicated that acetaldehyde showed competitive type
      inhibition of phosphomannomutase activity but not suppression of
      phosphomannomutase gene expression. CONCLUSIONS: By culturing HepG2 cells with
      acetaldehyde containing media, growth inhibition-dependent increase of CDT showed
      good correlation with reduced enzyme activity of phosphomannomutase. Acetaldehyde
      facilitated growth retardation, inhibition of phosphomannomutase activity, and
      increased secretion of CDT. The HepG2 cell line is useful as an in vitro model to
      investigate the pathophysiologic state of alcoholic liver damage and mechanisms
      of production as well as the physiologic role of CDT.

PMID- 12198373
TI  - Ethanol-induced Cas tyrosine phosphorylation and Fyn kinase activation in rat
      brain.
AB  - BACKGROUND: Tyrosine phosphorylation signaling has been reported to be involved
      in regulatory mechanisms of ethanol-induced modulation of the central nervous
      system. METHODS: We investigated the effect of ethanol administration on tyrosine
      phosphorylation signaling in rat brain and also examined the possible involvement
      of Fyn kinase in the process. RESULTS: Immunoprecipitation experiments showed
      that Crk-associated substrate (Cas) was tyrosine-phosphorylated in response to
      ethanol administration. Fyn kinase was shown to be activated by ethanol
      administration and to phosphorylate Cas on tyrosine residue in vitro.
      Furthermore, Fyn kinase was co-localized with Cas in rat cerebellum and cerebral
      cortex. CONCLUSIONS: Cas was tyrosine-phosphorylated in rat brain by ethanol
      administration, and Fyn kinase was most likely involved in the process.

PMID- 12198374
TI  - Ethanol-induced augmentation of annexin IV expression in rat C6 glioma and human
      A549 adenocarcinoma cells.
AB  - BACKGROUND: We previously reported that the amount of annexin IV significantly
      increased in the postmortem brains of alcoholics compared with controls. To
      investigate further whether ethanol directly affects cellular expression of
      annexins in a cell, we used cell lines and compared the amounts of annexins
      between ethanol-exposed and control cells. METHODS: Two kinds of cells (rat
      glioma C6 cells and human adenocarcinoma A549 cells) were used in the present
      study. Western blot analysis was performed to quantify expressed amounts of
      annexins using anti-annexin I, IV, and V antibodies. The mitochondrial enzyme
      (dehydrogenase) and caspase 3 activities were measured to assess cell damage
      (apoptosis) by ethanol. RESULTS: Expressive augmentation of annexin IV was shown
      in both C6 and A549 cells after a 5-hr exposure to 200 mM of ethanol, whereas
      amounts of annexins I and V were not changed. Both the mitochondrial
      dehydrogenase and caspase 3 activities were altered under the same conditions in
      C6 cells, indicating the induction of cell damage (apoptosis), whereas both of
      these enzyme activities were unchanged in A549 cells under the same conditions.
      CONCLUSIONS: The amount of annexin IV seemed to increase before the induction of
      cell damage by ethanol. Annexin IV might be one of the specific markers for the
      effect of ethanol.

PMID- 12198375
TI  - Michaelis-Menten elimination kinetics of acetaldehyde during ethanol oxidation.
AB  - BACKGROUND: Acetaldehyde (AcH) is a toxic metabolite of ethanol (EtOH). The
      pharmacokinetics of blood AcH during EtOH oxidation was studied with or without
      the administration of aldehyde dehydrogenase 2 inhibitor (cyanamide) in rabbits.
      METHODS: An bolus of EtOH saline solution (0.25, 0.5, 1.0, 1.5, and 2.0 g/kg) was
      injected intravenously. Cyanamide was administered intraperitoneally (25 mg/kg
      body weight) to the cyanamide-treated group. Blood EtOH and AcH concentrations
      were measured by using head-space gas chromatography. RESULTS: In the control
      group, the first peak of the blood AcH appeared immediately and the second
      elevation appeared 1 to 4 hr after administration at a high EtOH dose. The blood
      AcH levels other than the second elevation part were significantly correlated to
      the blood EtOH levels. In the cyanamide-treated group, a peak and a plateau
      formed at the time corresponding to the second peak in the control group. The
      peak and plateau concentration of AcH increased markedly. We attempted
      simultaneous curve fitting, using the five blood EtOH and AcH concentration-time
      curves, to determine the pharmacokinetic model. Consequently, the AcH elimination
      was best described by a Michaelis-Menten kinetic model in both groups.
      CONCLUSIONS: The blood AcH profile was suggested to consist of the first and
      second components that are related to the blood EtOH concentration itself and the
      metabolic formation of AcH, respectively. With higher EtOH doses or aldehyde
      dehydrogenase 2 inhibition, the second component becomes prominent as a result of
      the capacity-limited property of the metabolism of AcH, which is described by
      Michaelis-Menten elimination kinetics.

PMID- 12198376
TI  - Outcomes of small nodular lesions in heavy drinkers.
AB  - BACKGROUND: Increased detection of nodular lesions in patients not yet
      definitively diagnosed with hepatocellular carcinoma (HCC) has occurred with the
      use of advanced imaging techniques. In heavy drinkers, decrease in the size of
      nodular lesions during on-going observation, and negation of diagnoses of HCC
      after surgical resection have been reported, suggesting the need for caution in
      diagnosis in such cases. METHODS: The subjects were eight heavy drinkers with
      small nodular lesions, 20 mm or less in diameter. All patients were male, with a
      mean age of 53 years. Five had single and three had multiple nodular lesions.
      Five of the eight patients were followed up for more than 4 years after an
      initial biopsy, while three patients were recent cases. Of the three recent
      cases, two were positive for antibody to hepatitis C virus (HCV) and two had
      hypervascular nodular lesion. Biopsies were performed percutaneously, under
      ultrasonography, for histological diagnosis of all cases, and the recent cases
      were also assessed using a variety of imaging techniques. RESULTS: On initial
      biopsy, no atypism (NO) was found in two patients, and borderline lesions
      (Border) were present in six patients. Of the five cases followed up long-term,
      only one of the two with NO progressed to HCC, and the three with Border showed
      disappearance, decrease, and no change, respectively, during the follow-up
      period. Of the three recent cases, no changes in size or morphology as revealed
      by imaging were observed following biopsy. CONCLUSIONS: In heavy drinkers, no
      fixed relationship was observed between initial biopsy finding and clinical
      course, suggesting that indication for biopsy requires reassessment, refinement,
      and discussion. Furthermore, tumor staining may occur in hyperplastic nodules,
      which are histologically similar to early HCC by needle biopsy, and care needs to
      be exercised for diagnosis in heavy drinkers.

PMID- 12198377
TI  - Increase of rat alcohol drinking behavior depends on the age of drinking onset.
AB  - BACKGROUND: Although alcohol drinking onset in younger people is associated with
      an increased risk of alcohol-related injuries, other factors, such as habituation
      and susceptibility to alcohol, in the process of aging have not been adequately
      examined in animal models. In the present study, we determined whether age of
      drinking onset affected alcohol drinking behavior and led to alcohol tolerance in
      experimental animals, and extrapolated some of the findings to human alcohol
      drinking patterns. METHODS: In the first experiment, 18 rats that were naive to
      alcohol were tested at the age of 1, 4, and 10 months with 4 hr of access to 10%
      (v/v) alcohol. After the time access tests, these animals (1, 4, and 10 months of
      age) were housed individually and given free access to 10% alcohol solution and
      tap water. At 3 and 6 months later, all rats that had experienced alcohol
      drinking were studied for the voluntary consumption of the alcohol solution,
      alcohol preference, under the two-bottle method in a second experiment. RESULTS:
      In the 4-hr alcohol-access test, alcohol intake (g/kg/hr) was significantly
      increased at 0.5 and 1 hr in 1- and 4-month-old naive rats compared with 10-month
      old naive rats. The daily alcohol intake (g/kg/day) of rats with drinking onset
      at 1 month of age was significantly increased at 3 and 6 months after the
      voluntary alcohol consumption. The daily alcohol intake in the rats with drinking
      onset at 4 months of age was significantly increased at 6 months only. However,
      the daily alcohol intake did not change in the rats with drinking onset at 10
      months of age through the alcohol preference test. CONCLUSIONS: Alcohol drinking
      behavior in experimental animals depends on the age of alcohol drinking onset.

PMID- 12198378
TI  - Estriol enhances lipopolysaccharide-induced increases in nitric oxide production
      by Kupffer cells via mechanisms dependent on endotoxin.
AB  - BACKGROUND: Estriol causes sensitization of Kupffer cells to lipopolysaccharide
      (LPS) via mechanisms dependent on gut-derived LPS. Accordingly, this study
      examines the effect of estriol treatment on nitric oxide (NO) production from
      Kupffer cells. METHODS: Rats were given estriol (20 mg/kg body weight)
      intraperitoneally, and Kupffer cells were isolated 24 hr later. Some rats were
      treated for 4 days with 150 mg/kg/day of polymyxin B and 450 mg/kg/day of
      neomycin to prevent growth of intestinal bacteria, the primary source of
      endotoxin in the gastrointestinal tract. After addition of LPS, NO production by
      Kupffer cell was detected using a fluorescence indicator, DAF-2. RESULTS: Twenty
      four hours after estriol administration, LPS-induced NO production by Kupffer
      cells was enhanced as compared with control Kupffer cells. Sterilization of the
      gut with antibiotics blocked this enhancement. CONCLUSIONS: Estriol treatment in
      vivo enhances LPS-induced NO production in Kupffer cells.

PMID- 12198379
TI  - Oral contraceptives worsen endotoxin-induced liver injury in rats.
AB  - BACKGROUND: Oral contraceptives are widely used; however, these drugs
      occasionally cause liver injury. Recently, it was reported that estriol worsens
      alcoholic liver injury by the mechanism involving activation of Kupffer cells as
      a result of gut-derived endotoxin. However, the relationship between oral
      contraceptives and endotoxin-induced liver injury has not been elucidated. Here
      we show that oral contraceptives sensitize Kupffer cells via a mechanism
      dependent on increased gut permeability to endotoxin. METHODS: Female Wistar rats
      (200-250 g) were given intraperitoneally a combination of estradiol (35 ng/kg of
      17 alpha-Ethynylestradiol) and progesterone (2 microg/kg of Norethindrone), each
      dose being similar to that contained in oral contraceptives (EP treatment). After
      24 hr, a sublethal dose of lipopolysaccharide (LPS; 5 mg/kg) was injected via the
      tail vein. In some experiments, antibiotics (150 mg/kg/day of polymyxin B and 450
      mg/kg/day of neomycin) were administered orally for 4 days before EP treatment.
      Gut permeability was measured in isolated segments of ileum by translocation of
      horseradish peroxidase. Kupffer cells were isolated and cultured in RPMI 1640 +
      10% fetal bovine serum for 24 hr. After addition of LPS (100 ng/ml) to the
      culture medium, intracellular calcium concentration ([Ca2+](i) ) was measured
      with fura-2. RESULTS: Liver histology in rats given EP treatment
      intraperitoneally followed by an injection of LPS (5 mg/kg) 24 hr later revealed
      pronounced liver damage with massive necrosis. Whereas mean values of alanine
      aminotransferase (ALT) in the control, nontreated rats were 30 +/- 6 IU/liter,
      ALT increased to 75 +/- 21 IU/liter 24 hr after LPS injection. This increase was
      aggravated 6-fold (483 +/- 118 IU/liter; p< 0.05) by EP treatment. The EP
      treatment-induced increase in ALT was completely blocked by antibiotics (82 +/-
      26 IU/liter; p< 0.05). Gut permeability was increased approximately 10-fold with
      EP treatment. This increase in gut permeability was not altered by treatment with
      nonabsorbable antibiotics. In isolated Kupffer cells, LPS increased [Ca2+](i) of
      Kupffer cells in control rats from basal levels (36 +/- 8 nmol/liter) to 100 +/-
      8 nmol/liter. In contrast, the LPS-induced [Ca2+](i) elevation was approximately
      3-fold greater in the group given EP treatment before 24 hr (305 +/- 17
      nmol/liter; p< 0.05). This increase was also blocked completely by treatment with
      antibiotics (128 +/- 13 nmol/liter). Similar results were obtained for LPS
      induced tumor necrosis factor-alpha production by Kupffer cells from either
      control or EP treatment group. The increased tumor necrosis factor-alpha
      production as a result of EP treatment was blocked completely by antibiotics.
      CONCLUSIONS: These results indicate that EP treatment in vivo sensitizes Kupffer
      cells to LPS via a mechanism dependent on the portal increase of gut-derived
      endotoxin. This event suggests that oral contraceptives exacerbate alcoholic
      liver injury.

PMID- 12198380
TI  - Long-term ethanol feeding enhances susceptibility of the liver to orally
      administered lipopolysaccharides in rats.
AB  - BACKGROUND: Endotoxin has been implicated in the pathogenesis and progression of
      alcoholic liver disease. However, it is still unclear how long-term ethanol
      feeding affects absorption of endotoxin from the intestine and susceptibility of
      the liver to gut-derived endotoxin. The object of this study was to determine the
      effect of long-term ethanol feeding on hepatic susceptibility to orally
      administered endotoxin. METHODS: Male Wistar rats that weighed approximately 150
      g were pair-fed with an ethanol-containing liquid diet or a control diet for 35
      days. In some experiments, 0, 10, or 20 mg/kg of lipopolysaccharides (LPS) was
      added to the liquid diet for 7 days beginning on day 29. On day 36, the animals
      were killed for blood biochemistry and histologic examination of the liver. We
      also determined plasma endotoxin levels after 20 mg/kg of LPS administration
      using a gastric tube. In another set of experiments, we determined intestinal
      permeability using FD4 (fluorescein isothiocyanate-labeled dextran with an
      average molecular weight of 4000 D). RESULTS: With 10 mg/kg of LPS, serum alanine
      aminotransferase (ALT) and alkaline phosphatase (ALP) levels were significantly
      increased in the ethanol-fed rats but not in controls. After 20 mg/kg of LPS
      administration, more substantial increases in serum ALT and ALP levels were
      observed in ethanol-fed rats as compared with control diet-fed rats. Plasma
      endotoxin levels in long-term ethanol-fed rats were higher than those in control
      rats after intragastric administration of high-dose endotoxin (20 mg/kg).
      Furthermore, intestinal permeability to FD4 was increased by long-term ethanol
      administration. CONCLUSIONS: Long-term ethanol feeding increases intestinal
      permeability to and absorption of endotoxin, which can sequentially enhance
      hepatic susceptibility to orally administered endotoxin. This model has potential
      as a subclinical experimental model for the study of alcoholic liver disease.

PMID- 12198382
TI  - Experimental studies on the relationship between immune responses and liver
      damage induced by ethanol after immunization with homologous acetaldehyde
      adducts.
AB  - BACKGROUND: It has been considered that acetaldehyde (AcH) adducts induce liver
      injury through an immune response. Previous experimental studies showed that
      hepatic necrosis, inflammatory cell infiltration, and hepatic fibrosis were
      induced in guinea pigs immunized with heterologous human AcH adducts and ethanol
      feeding. AcH modification of foreign protein may markedly increase immunogenicity
      of the protein itself, leading to enhanced formation of immune complex and
      possible liver injury. The present study investigated whether immune responses
      and alcoholic liver disease would be induced in mice by immunization with mouse
      albumin-AcH adducts and ethanol feeding. METHODS: 6B6 mice were divided into six
      groups with or without immunization and ethanol feeding. Mice were immunized with
      mouse albumin-AcH adducts three times at 2-week intervals and fed ethanol for 10
      weeks. The stimulation index of [(3)H]thymidine uptake into lymphocytes cultured
      with mouse albumin or mouse albumin-AcH adducts was measured. Histologic findings
      of the liver were examined, and the plasma levels of aspartate transaminase and
      alanine aminotransferase were also measured. RESULTS: The stimulation index was
      increased remarkably in ethanol-fed mice that were immunized with mouse albumin
      AcH adducts. However, neither inflammatory cell infiltration nor hepatic necrosis
      was observed in the liver. There were also no differences in the plasma
      activities of aspartate transaminase and alanine aminotransferase between the
      group of mice regardless of ethanol feeding or immunization. CONCLUSION: Although
      marked immune responses were observed, no liver damage was induced by long-term
      ethanol feeding in our mouse model using AcH-homologous albumin adducts. These
      results suggest that homologous protein adducts may not induce liver injury by
      long-term ethanol feeding or may have lower immunogenicity than heterologous
      protein adducts. These results also suggest that nonreduced AcH adducts and/or a
      larger amount of ethanol may be needed for liver injury in this model.

PMID- 12198381
TI  - Effect of alcohol on the secretion of tumor necrosis factor-alpha by macrophages
      in the presence of rat serum.
AB  - BACKGROUND: It is suggested that endotoxin, proinflammatory cytokines, and
      lipopolysaccharide-binding protein (LBP) play an important role in the
      development of alcoholic liver disease. Our previous study showed that splenic
      macrophages were important for endotoxin uptake and excessive production of tumor
      necrosis factor (TNF) in rats given large amounts of alcohol. To determine the
      pathophysiological roles of macrophages in alcoholic liver disease, we examined
      the effect of ethanol on TNF-alpha secretion of rat Kupffer cells, alveolar
      macrophages, and peritoneal macrophages in the presence or absence of LBP.
      METHODS: Kupffer cells, alveolar macrophages, and peritoneal macrophages were
      isolated from male Sprague Dawley rats. After the preculture in the medium
      containing 0, 10, 50, and 100 mmol/liter of ethanol, TNF-alpha secretion by these
      cells incubated with 100 ng/ml of endotoxin in the presence or absence of LBP (1%
      rat serum) was determined. RESULTS: In the absence of LBP, an addition of ethanol
      to the medium suppressed TNF-alpha secretion of alveolar macrophages. Kupffer
      cells and peritoneal macrophages were less affected. Addition of LBP led to
      marked enhancement (7- to 24-fold) of TNF-alpha secretion of macrophages either
      with or without ethanol in the medium. Although ethanol tended to suppress TNF
      alpha secretion of these cells, alveolar macrophages were less affected in the
      presence of LBP. CONCLUSIONS: Serum LBP enhances the secretion of TNF-alpha by
      macrophages. Alveolar macrophages may be important for excessive production of
      TNF-alpha in chronic alcoholics with endotoxemia.

PMID- 12198383
TI  - Significant correlation between insulin resistance and serum gamma-glutamyl
      transpeptidase (gamma-GTP) activity in non-drinkers.
AB  - To understand the significance of elevated serum gamma-GTP levels, factors
      relevant to the serum gamma-GTP level were studied using data of health check-ups
      for the employees of a Japanese corporation. The gamma-GTP level was positively
      correlated with levels of various liver function tests including aspartate
      aminotransferase (AST) and alanine aminotransferase (ALT). Except for them, the
      gamma-GTP level was positively correlated with levels of insulin resistance, uric
      acid, total cholesterol, triglyceride, and body mass index. The correlation
      between the gamma-GTP level and LDL cholesterol was also observed only when
      subjects who drank more than 5 times a week were selectively studied. When non
      drinkers and opportunity drinkers were selectively studied, 63.6% of subjects
      whose gamma-GTP level was more than 120 IU/liter showed elevated insulin
      resistance levels. Multiple factors including insulin resistance may affect serum
      gamma-GTP activity in clinical subjects.

PMID- 12198384
TI  - Regional cerebral blood flow measured by the resting and vascular reserve (RVR)
      method in chronic alcoholics.
AB  - It has been reported that cerebral blood flow is decreased in chronic alcoholics
      without neurological diseases. We performed SPECT by the resting and vascular
      reserve (RVR) method in 11 chronic alcoholics (mean age 59.1 +/- 10.4, all males)
      and 11 age-matched healthy controls (mean age 58.8 +/- 10.1, all males). The
      resting and vascular reserve (RVR) method is a consecutive (99m)Tc-ECD SPECT
      study before and after acetazolamide administration with adjunctive radionuclide
      angiography, which is easy to perform for a routine clinical study and quite
      useful for evaluating regional cerebral blood flow and the cerebrovascular
      response to acetazolamide. Regional cerebral blood flows in almost all regions in
      the alcoholic group were lower than those in the control group. However, there
      were no significant differences in increased rates of blood flow in response to
      acetazolamide in almost all regions between the chronic alcoholic group and the
      control group. In both groups, the increased rates of blood flow in response to
      acetazolamide in the supratentorial region, cerebellum, and brain stem were 30
      40%, 20-25%, and 42-48%, respectively. The cerebrovascular response to
      acetazolamide in chronic alcoholics was not impaired, therefore the reduction of
      brain metabolism may be one of the important factors causing the decreased
      cerebral blood flow in chronic alcoholics.

PMID- 12198385
TI  - Alcohol-induced up-regulation of fibrinolytic activity and plasminogen activators
      in human monocytes.
AB  - BACKGROUND: Moderate alcohol consumption is associated with reduced risk for
      coronary heart disease. This may due, in part to increased fibrinolysis.
      Monocytes synthesize fibrinolytic proteins, tissue plasminogen activator (t-PA),
      urokinase plasminogen activator (u-PA), and their receptors. These studies were
      carried out to determine the effect of low alcohol on monocyte fibrinolytic
      activity and PA messenger RNA (mRNA) synthesis. METHODS: Peripheral blood
      monocytes and U937 cells were incubated in absence/presence of low alcohol (0.1%,
      v/v) for various times (0-1 hr), followed by incubations in the absence of
      alcohol (0-24 hr) before measurement of fibrinolytic activity and PA mRNA levels
      (reverse transcriptase polymerase chain reaction). RESULTS: Brief exposure (15
      min, 4 degrees C) of U937 cells to low alcohol resulted in an approximately 2- to
      3-fold increase (269.0 +/- 5.6 fmol/1 x 10 cells versus 656.0 +/- 94.0 fmol/1 x
      10 cells) in fibrinolytic activity. Preincubation of U937 cells and peripheral
      blood monocytes in low alcohol (1 hr, 37 degrees C) followed by incubation in the
      absence of alcohol (24 hr) resulted in a sustained approximately 4- to 5-fold
      increase (414.0 +/- 174.7 vs. 965.33.0 +/- 104.8 fmol/1 x 10 cells) and an
      approximately 3- to 4-fold (20.5 +/- 2.14 vs. 74 +/- 2.28 fmol/2 x 10 cells,
      respectively) increase in fibrinolytic activity. Preincubation of monocytes with
      low alcohol (1 hr, 37 degrees C) followed by incubation in the absence of alcohol
      (6 hr) resulted in an approximately 5- to 6-fold (0.06 +/- 0.02 vs. 0.42 +/-
      0.02) and an approximately 2- to 3-fold (0.89 +/- 0.04 vs. 2.07 +/- 0.29)
      increase in t-PA and u-PA mRNA (reverse transcriptase polymerase chain reaction;
      PA/glyceraldehyde-3-phosphate dehydrogenase ratio), respectively. CONCLUSIONS:
      These data suggest that low alcohol exerts a rapid, direct, and sustained effect
      on monocyte fibrinolytic activity, which may be, due in part, to increased
      monocyte t-PA/u-PA expression. These data provide a feasible molecular mechanism
      by which alcohol effects on monocyte fibrinolysis may contribute to the
      cardioprotective benefit associated with moderate alcohol consumption.

PMID- 12198386
TI  - Myocardial effects of ethanol consumption in the rat with streptozotocin-induced
      diabetes.
AB  - BACKGROUND: Rats with streptozotocin (STZ)-induced diabetes exhibit alterations
      in cardiac function, ventricular remodeling, and changes in cell signaling, which
      includes protein kinase C (PKC) isoforms. Moderate consumption of ethanol has a
      beneficial effect on cardiovascular outcomes in the general population, an effect
      that has recently been found to extend to patients with diabetes mellitus. We
      studied the effect of low-dose ethanol consumption on cardiac function, geometry,
      and PKC isoforms in the rat with STZ-induced diabetes. METHODS: Four groups of
      rats were studied over 8 to 10 weeks: control, STZ-induced diabetes, 12% (v/v)
      ethanol consumption, and STZ-induced diabetes plus 4% (v/v) ethanol consumption.
      Invasive hemodynamic measurements were performed; myocardial tissue was obtained
      for analysis for total PKC and cytosolic and membrane protein content of PKC
      alpha, PKC-delta, and PKC-epsilon, and two-dimensional and M-mode echocardiograms
      were obtained. RESULTS: Compared with rats with diabetes alone, consumption of 4%
      ethanol prevented the decrease in left ventricular dP/dt seen with diabetes
      alone, as well as the increase in left ventricular internal dimension. Up
      regulation of PKC-alpha, -delta, and -epsilon occurring in the diabetic animals
      was also prevented by ethanol consumption, whereas ethanol alone had no effect on
      PKC isoform pattern. CONCLUSIONS: These data suggest that STZ-induced cardiac
      remodeling and dysfunction are associated with increases in PKC activity,
      particularly PKC-alpha, -delta, and -epsilon, and that consumption of ethanol can
      prevent these changes.

PMID- 12198387
TI  - Alcohol consumption is associated with enrichment of high-density lipoprotein
      particles in polyunsaturated lipids and increased cholesterol esterification
      rate.
AB  - BACKGROUND: Alcohol consumption is associated with high levels of high-density
      lipoproteins (HDLs). Moreover, changes in the fatty acid patterns of red blood
      cell phospholipids and plasma lipids have been observed in drinkers. The
      objectives of this study were to characterize the composition of HDL particles
      with respect to lipid molecular species in regular wine drinkers and to assess
      the functional properties of those HDLs as regards key steps of reverse
      cholesterol transport. METHODS: Forty-six subjects were recruited in the frame of
      a population study performed in Toulouse, southern France, and a nutritional
      investigation, including daily alcohol consumption, was performed. Subjects were
      sorted according to their daily alcohol intake (0, < or =35, and >35 g/day),
      mostly as red wine. The plasma HDL fraction was isolated, and neutral lipid
      molecular lipids and phospholipid fatty acids were analyzed by gas liquid
      chromatography. Efflux of cellular cholesterol and rates of cholesterol
      esterification and cholesteryl ester transfers between lipoproteins were assayed
      in a cell-plasma incubation system. RESULTS: Wine drinking, at 47 g/day, was
      associated with an increase in HDL cholesterol and apolipoprotein A-I, but not
      with triglycerides. Isolated HDL displayed a 27% increase in all cholesteryl
      ester molecular species. The particles were also enriched in unsaturated
      phospholipids and, particularly, in those containing arachidonic (+30%) and
      eicosapentaenoic (+90%) acids. The plasma cholesterol esterification rate,
      reflecting lecithin cholesterol acyl transferase activity on HDL, was found to be
      higher (+27%) in drinkers than in nondrinkers, whereas the rate of cellular
      cholesterol efflux to plasma was identical. CONCLUSIONS: Regular wine consumption
      is associated with high levels of polyunsaturated lipids in HDL and with
      increases in the cholesterol esterification rate.

PMID- 12198388
TI  - The relationship between hippocampal acetylcholine release and cholinergic
      convulsant sensitivity in withdrawal seizure-prone and withdrawal seizure
      resistant selected mouse lines.
AB  - BACKGROUND: The septo-hippocampal cholinergic pathway has been implicated in
      epileptogenesis, and genetic factors influence the response to cholinergic
      agents, but limited data are available on cholinergic involvement in alcohol
      withdrawal severity. Thus, the relationship between cholinergic activity and
      responsiveness and alcohol withdrawal was investigated in a genetic animal model
      of ethanol withdrawal severity. METHODS: Cholinergic convulsant sensitivity was
      examined in alcohol-naive Withdrawal Seizure-Prone (WSP) and-Resistant (WSR)
      mice. Animals were administered nicotine, carbachol, or neostigmine via timed
      tail vein infusion, and the latencies to onset of tremor and clonus were recorded
      and converted to threshold dose. We also used microdialysis to measure basal and
      potassium-stimulated acetylcholine (ACh) release in the CA1 region of the
      hippocampus. Potassium was applied by reverse dialysis twice, separated by 75
      min. Hippocampal ACh also was measured during testing for handling-induced
      convulsions. RESULTS: Sensitivity to several convulsion endpoints induced by
      nicotine, carbachol, and neostigmine were significantly greater in WSR versus WSP
      mice. In microdialysis experiments, the lines did not differ in basal release of
      ACh, and 50 mM KCl increased ACh output in both lines of mice. However, the
      increase in release of ACh produced by the first application of KCl was 2-fold
      higher in WSP versus WSR mice. When hippocampal ACh was measured during testing
      for handling-induced convulsions, extracellular ACh was significantly elevated
      (192%) in WSP mice, but was nonsignificantly elevated (59%) in WSR mice.
      CONCLUSIONS: These results suggest that differences in cholinergic activity and
      postsynaptic sensitivity to cholinergic convulsants may be associated with
      ethanol withdrawal severity and implicate cholinergic mechanisms in alcohol
      withdrawal. Specifically, WSP mice may have lower sensitivity to cholinergic
      convulsants compared with WSR because of postsynaptic receptor desensitization
      brought on by higher activity of cholinergic neurons.

PMID- 12198389
TI  - Diurnal effects of acute and chronic administration of ethanol on sleep in rats.
AB  - BACKGROUND: Disturbances in sleep patterns are a complicating factor in recovery
      from alcoholism. The effects of acute and chronic alcohol treatments on sleep in
      rats were determined. METHODS: Adult male Sprague-Dawley rats were acclimated to
      a temperature-controlled chamber, and electromyograms and electroencephalograms
      (EEGs) were obtained during 23-hr recording sessions. Time spent in rapid eye
      movement sleep (REMS) and non-REM sleep (NREMS), EEG slow-wave activity (SWA)
      during NREMS, a spectral analysis of the EEG by fast Fourier transform, and brain
      temperatures were determined. RESULTS: Acute exposure to alcohol (2.3 and 3.0
      g/kg) by gastric intubation at the beginning of dark onset produced an increase
      in NREMS and a suppression of SWA. Spectral analysis revealed that during the
      first 4 hr there was a small increase in very-low-frequency bands (0.5-2 Hz),
      with a suppression of higher-frequency bands. This was followed by a suppression
      of low-frequency bands. A dose of 3.0 g/kg at light onset caused an increase in
      NREMS and a suppression of SWA. Spectral analysis revealed a suppression of low
      frequency bands throughout the first 12 hr of recording but no change on high
      frequency bands with light-onset alcohol. Chronic treatment with alcohol (6%
      alcohol in a liquid diet with pair-fed isocaloric controls) for 3 weeks produced
      an increase in NREMS and a decrease in EEG power density in frequency bands above
      2 Hz. Chronic alcohol also reduced the circadian variation of REMS, an effect
      that showed a rebound 1 week after the alcohol treatment was terminated. Two
      weeks after the alcohol treatment was stopped, NREMS and REMS values returned to
      baseline. CONCLUSIONS: These results demonstrate differences in the effect of
      acute alcohol on sleep depending on the time of administration and demonstrate
      that distinct alterations in sleep patterns are induced by chronic treatments in
      as little as 3 weeks.

PMID- 12198391
TI  - Differences in the responses of the pituitary beta-endorphin and cardiovascular
      system to ethanol and stress as a function of family history.
AB  - BACKGROUND: Genetic and environmental factors, such as stress, are important for
      the initiation and maintenance of heavy drinking, whereas beta-endorphin may be
      important in controlling alcohol consumption. These studies investigated the
      response of pituitary beta-endorphin to stress and the effect of alcohol on the
      stress response in subjects at low (LR) and high (HR) risk of alcoholism, as
      determined from their family history. METHODS: Twenty LR and 20 HR subjects were
      exposed to stress 30 min after ingestion of either a placebo or an alcohol drink.
      Plasma beta-endorphin was measured before and for 4 hr after the drink. Changes
      in the concentration of plasma beta-endorphin after ingestion of the placebo or
      alcohol drink alone served as controls to compare the stress-induced changes.
      Pulse and diastolic and systolic blood pressure were also measured. RESULTS: HR
      subjects presented higher baseline values of pulse and systolic blood pressure
      and lower plasma beta-endorphin than LR subjects. Stress induced a small increase
      in cardiovascular activity, whereas alcohol induced a stronger stimulation.
      Alcohol before stress did not prevent the stress-induced increase in
      cardiovascular activity. Stress, but not alcohol, increased the plasma beta
      endorphin concentration. LR subjects presented a higher stress-induced increase
      in plasma beta-endorphin and a faster recovery than HR subjects. Alcohol before
      stress attenuated the stress-induced increase in plasma beta-endorphin in both LR
      and HR subjects. This attenuation was stronger in LR subjects. CONCLUSIONS: Thus,
      there are differences in the response of beta-endorphin to stress and the effect
      of ethanol on stress responses as a function of a family history of alcoholism.

PMID- 12198390
TI  - Heart rate and motor-activating effects of orally self-administered ethanol in
      alcohol-preferring (P) rats.
AB  - BACKGROUND: Autonomic and behavioral arousals often accompany reinforcement.
      Additionally, contextual cues associated with alcohol consumption elicit
      increases in heart rate in alcoholics. This study examined changes in heart rate
      (HR) and motor activity before and during limited-access to ethanol, saccharin,
      or water in adult male alcohol-preferring (P) rats. METHODS: Adult male P rats
      were implanted with radiotelemetric transmitters to measure HR and motor
      activity. The experiment involved placing the animals in a test chamber for a 90
      min pretest period, with water available. Thereafter, the animals were given a 90
      min test session with access to one of three test solutions: water, 0.0125%
      saccharin, or 15% (v/v) ethanol (EtOH). After a week of habituation (water served
      as the test solution for all three groups), the animals were given their
      respective test solution for 3 weeks. RESULTS: Analyses of HR revealed that the
      saccharin and EtOH groups had significantly higher HR than the water group during
      the pretest period of the third test week. Both the saccharin and EtOH groups had
      significantly higher HR than the water group during the test period of all three
      test weeks. Analyses of motor activity revealed that the EtOH group displayed
      higher motor activity than the water and saccharin groups during the pretest
      period of the third test week. CONCLUSIONS: The data indicate that oral self
      administration of EtOH enhances behavioral and autonomic activation, compared
      with saccharin or water, in adult male P rats and support previous observations
      that changes in HR can be used as an index of reinforcement. Additionally, it
      seems that the behavioral and autonomic activation elicited by EtOH self
      administration can be conditioned to the environment in which EtOH was self
      administered. These findings parallel reports on cued reactivity (behavioral and
      autonomic activation) in alcoholics exposed to alcohol-associated stimuli.

PMID- 12198392
TI  - Nitrendipine blocks the nociceptive effects of chronically administered ethanol.
AB  - BACKGROUND: Calcium channel blockers prevent the development of tolerance to
      ethanol and prevent seizures and other signs of ethanol withdrawal. Calcium
      channels may also mediate the development of tolerance to the antinociceptive
      effects of ethanol. METHODS: A radiant-heat tail-flick assay was used to assess
      the effects of nitrendipine, a dihydropyridine L-type calcium channel blocker, on
      ethanol-induced changes in nociception in rats. Chronic effects of ethanol were
      tested in four groups of rats, which received 10 days of exposure to a liquid
      diet. The groups received twice-daily injections of saline or nitrendipine (1, 5,
      or 10 mg/kg). Tail-flick latencies were measured on days 0 (baseline), 2, 4, 6,
      8, and 10 and at 12 hr after removal of the liquid diet. RESULTS: Chronic
      exposure to ethanol produced maximal levels of antinociception by day 4 of
      exposure. The observed level of antinociception gradually decreased to baseline
      levels by day 8. Marked decreases in tail-flick latencies below baseline
      (hyperalgesia) were observed during ethanol withdrawal. Repeated administration
      of nitrendipine blocked the antinociceptive effects of chronic ethanol and
      prevented the hyperalgesia produced by ethanol withdrawal. The highest dose of
      nitrendipine (10 mg/kg, twice daily) reduced consumption of the ethanol diet.
      CONCLUSIONS: L-type calcium channel blockers block hyperalgesia during ethanol
      withdrawal and may mediate, at least in part, the antinociceptive effects of
      chronic ethanol.

PMID- 12198393
TI  - An evaluation of relations among antisocial behavior, psychopathic traits, and
      alcohol problems in incarcerated men.
AB  - BACKGROUND: The association between antisocial behavior and alcohol problems is
      well established, but the role that psychopathic traits and other factors such as
      drinking patterns and motives and family history play in this relationship has
      not been subjected to much empirical scrutiny. METHODS: A large sample (n=329) of
      male Federal Correctional Institution inmates participated in structured
      interviews designed to permit diagnosis of antisocial personality disorder and to
      assess facets of psychopathic personality as defined by the Hare Psychopathy
      Checklist-Revised. Prisoners also completed self-report questionnaires that
      addressed alcohol use, drinking problems, motives for drinking, and paternal
      alcoholism history. RESULTS: Analyses revealed that the relation between
      antisocial behavior and alcohol problems was moderated by scores on the emotional
      detachment component of psychopathy, and that self-descriptions of drinking for
      the purpose of coping with negative emotions mediated the positive relation
      between antisociality and self-reported alcohol problems. CONCLUSIONS: These
      findings highlight complexities in the link between antisociality and drinking
      problems and encourage consideration of distinct facets of psychopathy to enhance
      understanding of it. They further suggest possible mechanisms (e.g., paternal
      alcoholism history, coping motives) that may contribute to the development and
      maintenance of alcohol problems in criminal populations.

PMID- 12198394
TI  - Cortisol dysregulation and cognitive impairment in abstinent male alcoholics.
AB  - BACKGROUND: Alcoholics have impaired cortisol response to stress, indicating
      dysregulation in the extrahypothalamic systems responsible for activating
      cortisol secretion in response to stressor exposure. There is a growing
      literature indicating a relationship between hypothalamic-pituitary
      adrenocortical axis activity and neurocognitive functioning. This study examined
      the hypothesis that dysregulation of the hypothalamic-pituitary-adrenocortical
      axis may be associated with some neuropsychological impairments in alcoholics.
      METHODS: Serum cortisol was obtained during cognitive testing and after exposure
      to cold pressor and mental arithmetic stress in 48 male alcoholics abstinent for
      32 +/- 6.7 days and in 30 controls; cortisol was also obtained from 18 of the
      alcoholic patients during withdrawal. Neurocognitive tasks included the Wechsler
      Memory Scale and Wisconsin Card Sorting Test. Relationships among alcoholics'
      cognitive test scores, cortisol levels, and drinking practices were examined by
      correlation and regression analyses. RESULTS: Verbal memory deficits were more
      severe in alcoholics who had more withdrawals and ingested a higher typical
      quantity of alcohol during the prior year ( p< 0.05). Higher levels of cortisol
      during withdrawal, an index of withdrawal severity, were associated with more
      errors on the Wisconsin Card Sorting Test ( p< 0.005). As previously reported,
      the alcoholics had lower cortisol levels after stress compared with controls.
      Lower poststress cortisol levels were associated with poorer logical memory on
      the Wechsler Memory Scale and more errors on the Wisconsin Card Sorting Test ( p<
      0.05). Among controls, memory deficits occurred only in relation to higher
      poststress cortisol levels. CONCLUSIONS: Poorer cognitive performance in
      alcoholics was related to more withdrawals, heavier alcohol consumption, and
      higher cortisol levels during a recent withdrawal. Alcoholics' cognitive
      impairment was also related to attenuated stress cortisol responses. Altered
      stress regulation of the hypothalamic-pituitary-adrenal axis should be studied
      further as a potential factor related to impaired cognitive function in
      recovering alcoholics.

PMID- 12198395
TI  - Disruption of maternal behavior by alcohol intoxication in the lactating rat: a
      behavioral and metabolic analysis.
AB  - BACKGROUND: Preweanling rats exhibit clear behavioral signs of distress after
      interacting with an alcohol-intoxicated dam. Interestingly, behavioral reactivity
      of infants to the experience of alcohol in the nursing context decreases as a
      function of repeated alcohol administrations to the mother. In this study,
      maternal activities were examined when dams were exposed to repeated
      administrations of a subnarcoleptic alcohol dose. Maternal changes in alcohol
      metabolism were also analyzed as a function of repeated exposures to the drug.
      METHODS: During postpartum days 3, 5, 7, 9, 11, and 13, nursing dams received an
      intragastric administration of either 2.5 g/kg of alcohol or water. Maternal
      behaviors were evaluated (experiment 1). Blood alcohol levels (BALs) of the dams
      were determined on postpartum day 16 after all mothers received either an
      intragastric (experiment 2) or an intraperitoneal (experiment 3) dose of alcohol.
      The doses used (2.5 g/kg intragastrically and 1.5 g/kg intraperitoneally) were
      chosen because they promote similar peak BALs in dams naive to alcohol. RESULTS:
      Maternal behaviors were strongly affected by the state of intoxication.
      Nevertheless, these disruptions clearly subsided with progression of alcohol
      related experiences (experiment 1). Chromatographic analysis of alcohol
      metabolism indicated the development of tolerance in dams that had prior
      experience with alcohol (experiment 2). Changes in BALs as a function of prior
      experience with alcohol seemed related to first-pass alcohol metabolism rather
      than hepatic oxidative processes of the drug (experiments 2 and 3). CONCLUSIONS:
      When the dam first experiences a moderate state of alcohol intoxication, maternal
      behaviors are uniformly disrupted. Subsequent exposures to alcohol lead to
      maternal metabolic tolerance. In conjunction with previous studies, these data
      indicate that infantile reactivity to alcohol is dependent on how the members of
      the dam/pup dyad express or perceive ethanol's postabsorptive effects.

PMID- 12198396
TI  - Carbohydrate-deficient transferrin and gamma-glutamyltransferase for the
      detection and monitoring of alcohol use: results from a multisite study.
AB  - BACKGROUND: The purpose of this article is to evaluate the biological marker of
      heavy alcohol use, carbohydrate-deficient transferrin (CDT), in contrast to the
      older and more widely used gamma-glutamyltransferase (GGT) for the detection and
      monitoring of heavy alcohol use. METHODS: In this report, CDT and GGT sensitivity
      and specificity for heavy alcohol intake are examined in a large multisite study
      in which 444 recently admitted inpatient alcoholics were compared with 204
      matched social drinker controls. In addition, changes in these biomarkers were
      evaluated during an initial abstinence period and biweekly over 14 weeks of
      monitoring to compare changes in CDT and GGT during continued abstinence or
      relapse. RESULTS: CDT and GGT were comparable in identifying heavy alcohol
      consumption in men, but GGT appeared to be better for women. For both genders,
      when these markers were combined, there was better sensitivity than when used
      alone. CDT and GGT both decreased during 4 weeks of abstinence. When we used a
      30% increase from baseline abstinent levels as an indicator, CDT appeared
      marginally better than GGT at indicating relapse in men but not in women. For men
      in particular, relapse over the course of the study was best identified by
      evaluating changes (30% increase) in both markers simultaneously. CONCLUSIONS:
      These results support the utility of CDT, especially when used in conjunction
      with GGT, as an aid in detecting and monitoring heavy alcohol consumption.

PMID- 12198397
TI  - Co-occurrence of obsessive-compulsive personality traits in young and middle-aged
      Japanese alcohol-dependent men.
AB  - BACKGROUND: Previous studies may have underestimated the potential importance of
      the prevalence of obsessive-compulsive traits among persons with alcoholism.
      Although many studies have examined the characteristics of young alcoholics
      compared with middle-aged alcoholics, none has compared the prevalence of
      obsessive-compulsive traits in young and middle-aged alcoholics. METHODS: This
      study compared the prevalence of obsessive-compulsive traits (Leyton Obsessional
      Inventory) and depressive symptoms (Zung Self-Rating Depression Scale) among
      young (n=41) and middle-aged (n=34) hospitalized Japanese male alcoholics and in
      young (n=28) and middle-aged (n=25) nonalcoholic subjects. RESULTS: Both young
      and middle-aged male alcoholics reported more obsessive-compulsive personality
      traits and depressive symptoms than their comparison groups. However, the
      alcoholic subjects' obsessive-compulsive personality traits were not related to
      their level of depressive symptoms. CONCLUSIONS: Young and middle-aged male
      Japanese alcoholics have more obsessive-compulsive personality traits than
      nonalcoholic males of similar ages. Their alcohol-related psychological and
      behavioral characteristics may derive, in part, from their obsessive-compulsive
      symptoms.

PMID- 12198398
TI  - Coping among individuals seeking private chemical dependence treatment: gender
      differences and impact on length of stay in treatment.
AB  - BACKGROUND: Length of stay in treatment and coping skills are both predictive of
      chemical dependence and abuse treatment outcomes. However, little is known about
      whether coping strategies are related to length of stay in treatment. Because
      predictors of length of stay in treatment vary by gender, it also may be
      reasonable to expect gender differences in coping strategies as well as in the
      relationship between coping and LOS in treatment. METHODS: We examined gender
      differences in baseline coping strategies, and coping strategies as predictors of
      length of stay in treatment, among 747 (433 men, 314 women) individuals who
      entered chemical dependence and abuse treatment in a private, managed care
      facility. RESULTS: Women reported using more emotional discharge (behavioral
      attempts to reduce tension by expression of negative feelings), cognitive
      avoidance (cognitive attempts to avoid thinking realistically about the problem),
      resigned acceptance (cognitive attempts to react to the problem by accepting it),
      and seeking support/guidance (behavioral attempts to seek information, guidance,
      or support). Gender differences for emotional discharge disappeared after we
      controlled for depressive symptom and drug problem severities. Greater use of
      seeking alternative rewards (behavioral attempts to get involved in substitute
      activities and create new sources of satisfaction), less use of emotional
      discharge, and older age were significant predictors of longer length of stay,
      with no gender differences found. CONCLUSIONS: This study provides evidence for
      identifying and decreasing the use of emotional discharge early in treatment,
      possibly through the use of intervention strategies such as anger management,
      cognitive restructuring, or motivational interviewing, as well as encouraging an
      increase in participation in alternative activities.

PMID- 12198399
TI  - Serum sialic acid as a marker of alcohol consumption: effect of liver disease and
      heavy drinking.
AB  - BACKGROUND: Serum sialic acid (SA) has been suggested as a new marker of alcohol
      consumption. There are, however, only a few studies on the clinical value of such
      measurements. The relationship between serum SA and liver disease is also
      unknown. METHODS: We determined serum SA concentrations in a sample of 51
      alcoholics and 20 healthy controls by using high-performance liquid
      chromatography with an anion-exchange column and pulsed amperometric detection.
      The alcoholic sample included 32 patients with liver disease, the severity of
      which was assessed by previously established combined clinical, laboratory, and
      morphological indices. In addition, there were 19 heavy drinkers without
      significant liver disease despite a well documented history of excessive alcohol
      consumption. RESULTS: The (mean +/- SD) SA concentrations (1.449 +/- 0.3019
      mmol/liter) were significantly higher in the alcoholics than in the healthy
      controls (1.154 +/- 0.1702 mmol/liter). With the optimal cutoff limit for serum
      SA (1.425 mmol/liter), a specificity of 1.00 and sensitivity of 0.51 were
      obtained. The diagnostic accuracy of serum SA according to receiver operating
      characteristic analysis was good, with the area under the curve being 0.805
      (0.052). Unlike the traditional serum markers of alcohol consumption (gamma
      glutamyl transferase, carbohydrate-deficient transferrin, and aspartate amino
      transferase), serum SA was not found to be different between the alcoholics with
      or without liver disease. CONCLUSIONS: Our study suggests that serum SA is a
      sensitive marker of excessive alcohol consumption. Such measurements may also
      prove to be of value in conditions in which the results of the traditional
      markers reflect the severity of liver disease rather than alcohol consumption.

PMID- 12198400
TI  - Executive dysfunction and clinical outcome in chronic alcoholics.
AB  - BACKGROUND: The purpose of this study was to investigate which of 12
      neuropsychological tests predict alcoholic patients' alcohol-specific and/or
      alcoholic-nonspecific outcome. Our hypothesis was that the ecologically valid
      neuropsychological tests that measure executive function are better predictors of
      alcoholics' functional outcome. METHODS: We administered 12 neuropsychological
      tests to chronic alcoholics. Included in the tests were tasks of Reaction Time,
      Symbol Digit Modalities, Figure Position, Digit Span, Block Design, Trail Making,
      and six subtests of a battery called the Behavioral Assessment of the
      Dysexecutive Syndrome (BADS). Previous investigators have suggested that the BADS
      has ecological validity. Twenty-two male alcoholics were compared with 15
      nonalcoholic control subjects on these neuropsychological measures 7 weeks after
      detoxification. Two functional outcome indices, i.e., resumption of drinking and
      occupation, were evaluated 18 months after discharge. RESULTS: The total profile
      score and the score on three of the six subtests of the BADS were lower in
      alcoholics than in nonalcoholic controls. Alcoholics' performance on the BADS
      predicted alcohol-nonspecific outcome (occupation) but not alcohol-specific
      (drinking) outcome. In contrast, other neuropsychological tests did not predict
      either of the two outcome indices. CONCLUSIONS: The BADS total profile score is
      related to alcohol-nonspecific outcome but not to alcohol-specific outcome.

PMID- 12198402
TI  - 4-hydroxynonenal detoxification by mitochondrial glutathione S-transferase is
      compromised by short-term ethanol consumption in rats.
AB  - BACKGROUND: 4-Hydroxynonenal (HNE), a toxic lipid peroxidation product, has been
      implicated in mitochondrial damage in rat liver by ethanol consumption. The
      present study assessed the effects of short-term in vivo ethanol exposure on HNE
      detoxification by mitochondrial glutathione S-transferase (GST). METHODS: Male
      Sprague Dawley rats were administered 5 doses of ethanol (4 g/kg) at 12 hr
      intervals by gavage. Pair-fed rats that received isocaloric dextrose instead of
      ethanol served as controls. Mitochondrial and submitochondrial fractions were
      prepared from the livers. Mitochondrial contents of HNE and HNE-glutathione
      conjugate were measured by high-performance liquid chromatography. GST isoforms
      were identified by Western blots in submitochondrial fractions. RESULTS: Whereas
      there was an 80% increase in mitochondrial HNE content after ethanol consumption,
      there was a 42% decrease in the content of HNE-glutathione conjugate, compared
      with controls (p< 0.05). After ethanol exposure, the GST activities toward HNE in
      intact mitochondria and in the membranous fraction were decreased by 37% and 45%
      (p< 0.05), respectively, whereas that in the aqueous fraction was unchanged.
      Kinetic analysis of HNE conjugation by the membrane-associated GST showed that
      ethanol decreased the V(max) nearly by half (p< 0.05), whereas it did not affect
      the K(m). HNE conjugation by the aqueous GST demonstrated a higher K(m) than that
      of the membrane-associated GST, although its kinetics were not significantly
      altered by ethanol. Immunochemical analysis with Western blots demonstrated that
      both the membranous and the aqueous fractions of mitochondria contain GST-alpha
      and GST-mu isoforms, whereas GST-pi was absent. CONCLUSIONS: HNE detoxification
      by mitochondrial GST is compromised by short-term ethanol consumption, which may
      contribute to elevated mitochondrial HNE content and hence its toxicity in the
      ethanol-exposed liver.

PMID- 12198401
TI  - Glutathione replacement preserves the functional surfactant phospholipid pool
      size and decreases sepsis-mediated lung dysfunction in ethanol-fed rats.
AB  - BACKGROUND: Alcohol abuse increases the incidence of acute respiratory distress
      syndrome (ARDS). Previous evidence from our laboratory links ethanol-mediated
      glutathione depletion to impaired surfactant production by alveolar epithelial
      cells in vitro and to endotoxin-mediated edematous injury in isolated lungs ex
      vivo. ARDS patients have an imbalance between the inactive small aggregate (SA)
      and the bioactive large aggregate (LA) forms of surfactant phospholipid (as
      reflected by increased SA/LA ratios). Therefore, we hypothesized that ethanol
      ingestion, via glutathione depletion, could alter surfactant phospholipid
      distribution between LA and SA forms and thereby exacerbate sepsis-mediated lung
      dysfunction in vivo. METHODS: Rats fed an isocaloric diet with or without ethanol
      (36% total calories) for 6 weeks were made septic via cecal ligation and
      perforation. Some ethanol-fed rats had their diets supplemented with the
      glutathione precursor procysteine (>L-2-oxothiaxolidine-4-carboxylate). Sepsis
      physiology was assessed by determining respiratory rates, arterial blood
      pressures, and plasma lactate levels, and lung dysfunction was assessed by
      determining lung lavage fluid protein levels (index of alveolar
      endothelial/epithelial barrier disruption), arterial hypoxemia (index of impaired
      gas exchange) and surfactant phospholipid SA and LA fractions (index of the
      alveolar epithelium's ability to maintain a functional surfactant pool during
      sepsis). RESULTS: Ethanol ingestion decreased (p< 0.05) lung lavage fluid
      glutathione levels, and this defect was prevented by procysteine. Although
      ethanol ingestion had no effect (p< 0.05) on any of the indices of sepsis, it
      increased (p< 0.05) lung lavage fluid protein levels, worsened hypoxemia, and
      decreased the functional (LA) surfactant phospholipid pool after sepsis, all of
      which was prevented by procysteine. CONCLUSIONS: Ethanol ingestion, via
      glutathione depletion, increased sepsis-mediated lung dysfunction, and these
      effects could contribute to the increased risk of ARDS seen in alcoholic
      patients.

PMID- 12198403
TI  - Accentuated decrease in social interaction in rats subjected to repeated ethanol
      withdrawals.
AB  - BACKGROUND: Previous work has shown that repeated withdrawals from chronic
      ethanol exposure can kindle seizures in rodents. In this article, the effects of
      a three-cycle model of ethanol exposure and withdrawal on the social interaction
      test of anxiety are summarized. METHODS: Rats were exposed to ethanol (7% or
      4.5%) diets over three periods of 5 days, with 2 days of withdrawal between
      cycles. Between 5 and 6 hr after the ethanol was removed, pairs of rats were
      placed in open field chambers for the assessment of social interaction behavior
      and locomotor activity. RESULTS: After the third cycle of ethanol (7%)
      presentation, both male and female rats exhibited lower social interaction
      behavior (more anxiety) and activity than after a single cycle. Rats exposed to a
      similar amount of ethanol but tested while ethanol was still available did not
      exhibit a reduction in social interaction. The decrease in social interaction was
      still present for up to 24 hr but had disappeared by 48 hr after ethanol was
      withdrawn. When rats were allowed 8 or 16 days to recover from the effects of the
      three-cycle protocol, a further exposure to 5 days of 7% ethanol diet resulted in
      a reduction in social interaction on withdrawal similar to that seen from the
      three-cycle protocol. In contrast, rats exposed continuously to 7% ethanol diet
      for 15 consecutive days exhibited higher levels of social interaction when
      maintained on control diet for 8 or 16 days and then reexposed to ethanol. Rats
      that were exposed to the three-cycle protocol and allowed 32 days to recover
      before being reexposed to ethanol still had a partial deficit in social
      interaction. Finally, animals subjected to repeated withdrawals from 4.5% ethanol
      exhibited a reduction in social interaction without a change in activity after
      the final withdrawal from ethanol, whereas rats exposed continuously to a 4.5%
      ethanol diet did not exhibit a reduction in social interaction or activity.
      Neither blood ethanol concentrations nor changes in body weight could account for
      these behavioral differences. CONCLUSION: Repeated withdrawal from ethanol can
      lead to accentuated or more persistent anxiety-like behavior in rats, as
      indicated by a decrease in social interaction. The withdrawal-induced decrease in
      locomotor activity is not accentuated by repeated withdrawals. This model of
      repeated withdrawals from ethanol may prove useful in defining the neurochemical
      basis of this accentuation.

PMID- 12198404
TI  - The effects of chronic alcohol consumption and exercise on the skeleton of adult
      male rats.
AB  - BACKGROUND: Lifestyle factors are known to affect skeletal development and
      integrity. Specifically, running has been reported to increase risk of fatigue
      fractures, whereas chronic alcohol consumption has been shown to reduce bone
      formation and bone mass. The combined effect of exercise and alcohol on the
      skeleton has yet to be explored, although alcohol consumption is common among
      certain physically active populations (e.g., military recruits, college
      athletes). It was hypothesized that chronic alcohol consumption would accentuate
      the inherent risk associated with endurance running exercise. METHODS: Six-month
      old male Sprague Dawley rats were assigned to one of five groups: baseline,
      exercise-alcohol diet, exercise-normal diet, sham-alcohol diet, and sham-normal
      diet. Alcohol-fed rats (35% caloric intake) received a liquid diet ad libitum.
      Normal animals were pair-fed the identical diet with a maltose dextrin caloric
      substitute. Exercise was conducted on a motorized treadmill 5 days/wk for 16
      weeks. Sham rats were placed on a stationary treadmill for matching time periods.
      Fluorochrome labels were administered 3 days before baseline and at 10 and 2 days
      before animals were killed. Heart, soleus, and rectus femoris muscles were wet
      weighed to assess the effects of training. Tibiae were collected for static and
      dynamic histomorphometric measurements on cancellous and cortical bone. RESULTS:
      Muscle weights were larger in the exercised rats versus the sham rats. Alcohol
      had no significant effect on skeletal muscle weight but did result in larger
      heart weights in both alcohol-treated groups. Cancellous and periosteal bone
      formation rates were significantly decreased in the alcohol-fed rats versus rats
      on the normal diet and were associated with a significant reduction in trabecular
      thickness in the tibial metaphysis. Cortical and cross-sectional areas were also
      significantly lower in the alcohol-fed groups compared with the non-alcohol-fed
      groups. Exercise had no significant effect on cancellous or cortical bone
      measurements. CONCLUSIONS: Chronic alcohol consumption significantly reduced bone
      formation. Exercise had no effect on the bone and did not attenuate any of the
      negative effects of alcohol. The results suggest that alcohol consumption weakens
      the skeleton and increases the incidence of endurance-exercise-related bone
      injuries. Thus, individuals who are participating in endurance exercise and
      consuming alcohol may be at greater risk for exercise-related skeletal injuries.
      Further investigation of the potential for alcohol to induce detrimental effects
      on the hearts of individuals participating in endurance exercise is indicated.

PMID- 12198405
TI  - Brain catalase inhibition blocks ethanol-related decrease of blood luteinizing
      hormone levels in mice.
AB  - BACKGROUND: It has been demonstrated that ethanol decreases blood luteinizing
      hormone (LH) levels in rodents. This effect seems to be produced by the capacity
      of ethanol to release beta-endorphins from the hypothalamic arcuate nucleus and,
      in a second step, by a mu-receptor-mediated inhibitory effect of these peptides
      on hypothalamic LH-releasing hormone-synthesizing neurons. However, it has been
      reported that, in primary hypothalamic cultures, the ethanol-produced beta
      endorphin release is mediated by the enzyme catalase. Therefore, the aim of this
      study was to assess whether catalase inhibition modifies ethanol effects on blood
      LH levels. METHODS: Swiss albino mice were pretreated with the catalase inhibitor
      3-amino-1,2,4-triazole (AT; 0.0-0.5 g/kg) and, 3.5 hr later, saline, ethanol (2.5
      g/kg), or morphine (30 mg/kg) was administered. Blood samples were collected 2 hr
      after ethanol administration, and LH levels were immunoenzymatically assayed.
      RESULTS: The catalase inhibitor AT dose-dependently blocked the ethanol-produced
      decrease in blood LH levels without altering those observed after saline or
      morphine administration. This effect was highly correlated with the decrease in
      brain catalase activity produced by AT. CONCLUSIONS: These results show an
      antagonistic effect between AT and ethanol on blood LH levels and suggest a role
      of brain catalase activity on this effect of ethanol. Data are discussed in terms
      of a possible functional relationship between brain catalase and beta-endorphins
      in the mediation of some of the psychopharmacological consequences observed after
      ethanol administration.

PMID- 12198406
TI  - Effects of ethanol and transforming growth factor beta (TGF beta) on neuronal
      proliferation and nCAM expression.
AB  - BACKGROUND Developmental events targeted by ethanol are cell proliferation,
      neuronal migration, and neurite outgrowth; the latter processes being mediated by
      neural cell adhesion molecule (nCAM). TGFbeta1 affects all three of these events.
      Therefore, the effects of ethanol on transforming growth factor (TGF) beta1
      mediated activities in neocortical neurons in vitro were examined. METHODS
      Primary cultures of cortical neurons were obtained from 16-day-old fetuses and
      were treated with TGFbeta1 (0 or 10 ng/ml) and ethanol (0 or 400 mg/dl) for 48
      hr. The effects of these substances on cell numbers, [ H]thymidine incorporation,
      and the expression of nCAM were determined. RESULTS Both cell growth (the change
      in cell numbers over time) and cell proliferation were inhibited by TGFbeta1 and
      ethanol. The action of these two anti-mitogenic factors was additive. In
      contrast, TGFbeta1 also promoted the expression of three isoforms of nCAM.
      Likewise, ethanol also up-regulated nCAM expression. On the other hand, ethanol
      blocked TGFbeta1-mediated nCAM expression, particularly of the 120 and 180 kDa
      isoforms. CONCLUSIONS TGFbeta ligands inhibit neuronal proliferation and
      stimulate the expression of cell adhesion proteins that promote the movement of
      postmitotic neurons and process outgrowth. Ethanol alters these phenomena as
      well. Thus, in neurons, as in astrocytes, TGFbeta1 and ethanol may interact.

PMID- 12198407
TI  - Ethanol induces morphological and dynamic changes on in vivo and in vitro neural
      crest cells.
AB  - BACKGROUND: Fetal alcohol syndrome (FAS) is an embryopathology related to
      maternal alcohol drinking. The information concerning the factors involved in the
      prenatal mechanisms of ethanol action at the cellular and molecular levels is
      scarce. Because several abnormal changes in FAS involve regions colonized by cell
      lineages derived from neural crest cells (NCCs), it is reasonable to propose that
      epigenetic alteration of this cell population can represent an important
      component of the etiopathogeny. The aim of this work was to evaluate the direct
      effect of ethanol on a chick embryo model, as well as on in vitro NCC morphology
      and dynamic behavior. METHODS: After ethanol treatment, in ovo or cultured chick
      embryos were used to determine the anatomical development of and to quantify the
      migratory parameters and apoptosis of NCCs. Scanning electron microscopy was
      performed on ethanol-perfused (and control) cultures of cephalic and trunk NCCs;
      the actin cytoskeleton was evaluated, and morphometric and dynamic parameters
      were determined after time-lapse videorecording. Recovery capacity after ethanol
      treatment was also determined. RESULTS: Chick embryos submitted to conditions
      sufficient to induce FAS in mammals displayed developmental disruptions
      frequently accompanied by cephalic/facial anomalies. In vitro studies also
      indicated that cephalic and trunk NCCs exposed to ethanol exhibited significant
      and permanent changes regarding cell shape, surface morphology, apoptotic cell
      death, cytoskeleton, and distance and velocity traveled, as well as an abnormal
      pattern of migration. CONCLUSIONS: Taking into account that even a limited period
      of abnormal behavior may imply serious consequences in the final cues of an
      embryonic cell population, our results indicate that the biological effects of
      ethanol on early development-even during a short time-could induce permanent
      ontogenetic perturbations of NCCs, with potentially dramatic effects on embryonic
      morphogenesis. These results support an important participation of NCCs in the
      etiopathogeny of FAS.

PMID- 12198408
TI  - Self-reported subjective perception of intoxication reflects family history of
      alcoholism when breath alcohol levels are constant.
AB  - BACKGROUND: The premise of this study is that the increased familial risk for
      alcoholism is associated with genetic determinants of the response to alcohol,
      characterized by sensitivity and adaptation. Following a single administration,
      sensitivity is the initial response to alcohol, expressed as the change in
      dependent measures from baseline. Adaptation of dependent measures within a
      single exposure to alcohol can be expressed as acute tolerance (recovery of
      dependent measures toward baseline values) or sensitization (movement of
      dependent measure further away from baseline values). This study tested the
      hypothesis that family history-positive (FHP) subjects are more sensitive and
      more adaptive to alcohol compared with family history-negative (FHN) subjects.
      METHODS: The initial response and development of adaptation to alcohol were
      assessed by using self-reported subjective perceptions during a breath alcohol
      concentration (BrAC) clamp of 60 mg%. The Biphasic Alcohol Effects Scale, the
      Sensation Scale and a visual analog scale of intoxication were acquired at
      baseline, after the BrAC clamp was established, and after maintenance of the
      clamp for 105 min. RESULTS: FHP subjects were more sensitive to alcohol compared
      with FHNs, as evidenced by greater changes in feelings of intoxication when the
      BrAC clamp was initially achieved. While the clamp was maintained, the FHP
      subjects adapted to the effects of alcohol and their perceptions of intoxication
      became indistinguishable from those of the FHN subjects. The FHP subjects had
      developed acute tolerance to alcohol, whereas the FHN subjects did not. Other
      self-reported perceptions of alcohol's effects did not distinguish between the
      groups. CONCLUSIONS: A differential family history of alcoholism was reflected in
      self-reported subjective perceptions of intoxication when the brain's exposure to
      a specified concentration of alcohol was held constant (BrAC of 60 mg%). FHP
      subjects reported greater intoxication after alcohol and subsequently developed
      acute tolerance to alcohol compared with FHN subjects.

PMID- 12198409
TI  - Administration of low doses of MK-801 during ethanol withdrawal in the developing
      rat pup attenuates alcohol's teratogenic effects.
AB  - BACKGROUND: Alcohol exposure during development can produce severe and long
      lasting central nervous system damage and consequent behavioral alterations.
      Recent evidence suggests that NMDA receptor-mediated excitotoxicity during
      periods of withdrawal may contribute to this damage. We have demonstrated that
      blocking the NMDA receptor with MK-801 during alcohol withdrawal can attenuate
      ethanol's adverse effects on behavioral development in the rat. This study
      examined the dose dependency of MK-801's ability to mitigate ethanol's
      teratogenic effects. METHODS: Neonatal rat pups were exposed to 6.0 g/kg of
      ethanol in a binge-like manner on postnatal day (PD) 6, a period of brain
      development equivalent to a portion of the human third trimester. Alcohol
      administration was accomplished with an artificial rearing procedure. Twenty-one
      hours after ethanol treatment, pups were injected intraperitoneally with one of
      four doses of MK-801 (0.05, 0.1, 0.5, or 1.0 mg/kg) or saline vehicle. An
      artificially reared control and a normally reared control group were included. On
      PD 18-19, activity level was monitored, and on PD 40-42, serial spatial
      discrimination reversal learning was assessed. RESULTS: Alcohol exposure on PD 6
      produced significant increases in activity level and deficits in reversal
      learning. These alcohol-induced behavioral alterations were significantly
      attenuated in subjects treated with one of the three lower doses (0.05-0.5 mg/kg)
      of MK-801 during withdrawal. The performance of ethanol-exposed subjects treated
      with the high dose of MK-801 (1.0 mg/kg) did not differ from that of the Ethanol
      Only group. CONCLUSIONS: These data suggest that alterations in NMDA receptor
      activation during alcohol withdrawal contribute to the neuropathology and
      consequent behavioral alterations associated with developmental alcohol exposure.
      These data have important implications for pregnant women and newborns undergoing
      ethanol withdrawal.

PMID- 12198410
TI  - Unilateral fusion of the frontosphenoidal suture: a rare cause of synostotic
      frontal plagiocephaly.
AB  - Unilateral coronal synostosis is the common appellation for premature, one-sided
      fusion of the frontoparietal suture-the most common cause of synostotic frontal
      plagiocephaly. However, frontal asymmetry can also result from isolated fusion
      across the anterior cranial base without involvement of the frontoparietal
      suture. This article describes three patients with localized synostosis of the
      frontosphenoidal suture, the medial extension of the coronal ring. Two patients
      were initially misdiagnosed as having unilateral coronal synostosis and the other
      as having deformational frontal plagiocephaly. The patients had variable frontal
      flattening, with depression and recession of the ipsilateral orbital rim. The
      nasal root was midline or slightly deviated to the contralateral side. The
      sagittal position of the ipsilateral malar eminence was slightly retruded in one
      patient and symmetric in the other two. The auricular position was symmetric in
      the sagittal plane for all patients. In all three patients, computed tomography
      examination demonstrated a patent frontoparietal suture and fusion of the
      frontosphenoidal suture (basilar hemicoronal ring). Two patients had involvement
      of contiguous sutures: one had fusion extending to the sphenoethmoidal suture and
      the other's involved part of the sphenozygomatic suture. The sagittal suture was
      midline in all patients. In summary, synostotic frontal plagiocephaly denotes a
      relatively broad phenotypic spectrum that includes unilateral coronal synostosis
      and more isolated fusions in the basilar coronal ring. The physical findings
      resulting from frontosphenoidal synostosis are unique, yet careful evaluation
      will minimize confusion with other causes of asymmetric frontal flattening.
      Proper diagnosis necessitates awareness of this uncommon entity and requires
      focused computed tomographic assessment.

PMID- 12198411
TI  - Incorporation of titanium mesh in orbital and midface reconstruction.
AB  - Several authors have demonstrated the safety and effectiveness of titanium in
      orbital reconstruction. One question posed by clinicians is what happens to large
      pieces of titanium in communication with the paranasal sinuses or nasal-oral
      pharyngeal area. This question becomes increasingly relevant as titanium is used
      to reconstruct extensive defects for which the destruction of bony architecture
      requires the placement of mesh in proximity to these areas. The objective of this
      study was to examine the gross and histologic soft-tissue response to large
      segments of titanium mesh in the setting of orbital and midface reconstruction,
      particularly when exposed to the nasal-oral-pharyngeal area and paranasal
      sinuses. In this study, large segments of titanium mesh were used in eight
      patients to reconstruct orbital and midface defects, with direct communication
      between the mesh and nasal-oral-pharyngeal area and paranasal sinuses. Four
      patients had suffered self-inflicted gunshot wounds; as a result, much of their
      midface was missing, including the inferior and medial orbital floor, maxilla,
      nose, naso-orbital-ethmoid complex, and hard palate. Extensive sheets of titanium
      mesh were used to reconstruct their medial and inferior orbital walls, nasal
      bridge, and maxilla. In the fifth patient, titanium mesh was used to reconstruct
      the maxilla after resection of a squamous cell carcinoma of the nasolacrimal
      duct. In the sixth and seventh patients, mesh was used to reconstruct the nasal
      bridge after severely comminuted nasal fractures resulted in the loss of bone and
      mucosa. Finally, the eighth patient had titanium mesh used to replace cocaine
      induced bone loss involving the left medial orbital floor and wall and part of
      the maxilla. On gross examination by either endoscopy or direct inspection, all
      eight patients had rapid soft-tissue incorporation of the titanium mesh. Initial
      examination typically revealed budding of soft tissue through mesh interstices,
      followed by progressive incorporation. One patient's mesh was covered in only 15
      days. Two patients underwent biopsies of this newly formed soft tissue. One had
      biopsies performed at 3, 15, and 31 months after the original operation. Biopsy
      examination at 3 months revealed incorporation of the titanium with fibrous soft
      tissue covered by ciliated respiratory epithelium, goblet cells, and squamous
      epithelium with metaplasia. In addition, the dense, acute inflammation present at
      3 months evolved into mild, chronic inflammation at 31 months. The second patient
      had a single biopsy 4 months after secondary orbital reconstruction for delayed
      enophthalmos. Biopsy examination revealed a fibrous soft-tissue sheath lined by
      squamous epithelium with metaplasia. Again, mild chronic inflammation was present
      within the soft tissue. This study provides evidence of titanium's compatibility
      with soft tissue. The mesh underwent progressive incorporation with soft tissue
      that was then resurfaced by indigenous cells, including respiratory epithelia and
      goblet cells. This phenomenon occurred despite communication with the nasal-oral
      pharyngeal area and paranasal sinuses.

PMID- 12198413
TI  - Combined otoplasty technique: chondrocutaneous conchal resection as the
      cornerstone to correction of the prominent ear.
AB  - The failure to correctly analyze the complex deformity that comprises the
      prominent ear is the most common cause of the undesired surgical result.
      Recognizing conchal hypertrophy as one of the leading causes of the prominent ear
      deformity has led to a versatile and reproducible otoplasty technique that is
      easily modified to the common side-to-side variation in deformity. From January
      of 1993 to August of 2000, chondrocutaneous conchal resection has been used as
      the cornerstone to a combined sequence of maneuvers in otoplasty. The operation
      was performed on 47 patients (40 bilateral cases and 7 unilateral), and the total
      number of ears operated on was 87. There were three complications requiring
      revision surgery, and follow-up periods ranged from 6 months to 7 years, with all
      patients achieving a satisfactory result. Detailed methods of chondrocutaneous
      conchal resection along with the sequence of the authors' combined otoplasty
      techniques are presented.

PMID- 12198415
TI  - The timing of neovascularization in fingertip replantation by external bleeding.
AB  - To overcome venous congestion in fingertip replantation with no venous
      anastomosis, the authors have used a salvage procedure that consists of
      continuous external bleeding through a stab incision on the paraungual area and
      dripping a heparinized saline solution at the incision site to maintain external
      bleeding. Because this method requires continuous bleeding for a certain period
      of time, it may be a great burden on the patient; therefore, it is most important
      to minimize the duration of bleeding. Many authors have studied the timing of the
      new venous channel formation of the flap. However, to our knowledge, a study on
      fingertip replantations has not yet been performed. From June of 1985 to November
      of 1999, the authors performed fingertip replantations on 144 fingers of 137
      patients using our salvage procedure at Korea University Guro Hospital. Among the
      144 fingers, 101 fingers of 96 patients were successfully transplanted, including
      those with partial necrosis. The authors reviewed the medical records of these
      101 fingers retrospectively; they compared and analyzed the necessary duration of
      external bleeding according to sex, age, level of injury, cause of amputation,
      and the type of injury. The average period of the salvage procedure was 7.6 days.
      Regarding age, the shortest period (5.5 days) was required for patients younger
      than 10 years. On the basis of the types of injuries, the duration of bleeding
      was shortest for the guillotine injury group (5.9 days) compared with crush (8.2
      days) or avulsion (8.0 days) injuries. Sex and level of injury did not make much
      difference in the duration of the procedure.

PMID- 12198416
TI  - The role of intrinsic muscle flaps of the foot for bone coverage in foot and
      ankle defects in diabetic and nondiabetic patients.
AB  - Local muscle flaps, pioneered by Ger in the late 1960s, were extensively used for
      foot and ankle reconstruction until the late 1970s when, with the evolution of
      microsurgery, microsurgical free flaps became the reconstructive method of
      choice. To assess whether the current underuse of local muscle flaps in foot and
      ankle surgery is justified, the authors identified from the Georgetown Limb
      Salvage Registry all patients who underwent foot and ankle reconstruction with
      local muscle flaps and microsurgical free flaps from 1990 through 1998. By
      protocol, flap coverage was the reconstructive choice for defects with exposed
      tendons, joints, or bone. Local muscle flaps were selected over free flaps if the
      defect was small (3 x 6 cm or less) and within reach of the local muscle flap.
      During the same time frame, the authors performed 45 free flaps (96 percent
      success rate) in the same areas when the defects were too large or out of reach
      of local muscle flaps. Thirty-two consecutive patients underwent local muscle
      flap reconstruction for 19 diabetic wounds and 13 traumatic wounds. All wounds,
      after debridement, had exposed bone at their base, with osteomyelitis being
      present in 52 percent of the diabetic wounds and in 70 percent of the nondiabetic
      wounds. Wounds were located in the hindfoot (47 percent), midfoot (44 percent),
      and ankle (9 percent). Vascular disease was more prevalent in the diabetic group,
      in which 42 percent of the affected limbs required revascularization procedures
      before reconstruction (versus 7 percent in the nondiabetic group). Subsequently,
      83 total operations were required to heal the wounds, of which 46 percent were
      limited to debridement only. Thirty-four pedicled muscle flaps were used: 19
      abductor digiti minimi (56 percent), nine abductor hallucis (26 percent), three
      extensor digitorum brevis (9 percent), two flexor digitorum brevis (6 percent),
      and one flexor digiti minimi (3 percent). An additional skin graft for complete
      coverage was required in 18 patients (53 percent). One patient died and one flap
      developed distal necrosis, for a 96 percent success rate. The complication rate
      was 26 percent and included patient death, dehiscence, and partial flap or split
      thickness skin graft loss. Twenty-nine of the 32 wounds healed. One patient died
      in the postoperative period; in two others the wounds failed to heal and required
      below-knee amputations, for an overall limb salvage rate of 91 percent. Diabetes
      did not significantly affect healing and limb salvage rates. Diabetes, however,
      did affect healing times (twofold increase), length of stay (2.7 times as long),
      and long-term survival (63 percent survival in diabetic patients versus 100
      percent in the trauma group). Local muscle flaps provide a simpler, less
      expensive, and successful alternative to microsurgical free flaps for foot and
      ankle defects that have exposed bone (with or without osteomyelitis), tendon, or
      joint at their base. Diabetes does not appear to adversely affect the
      effectiveness of these flaps. Local muscle flaps should remain on the forefront
      of possible reconstructive options when treating small foot and ankle wounds that
      have exposed bone, tendon, or joint.

PMID- 12198418
TI  - A classification system and reconstructive algorithm for acquired vaginal
      defects.
AB  - Although multiple flaps have been used for vaginal reconstruction, a logical
      approach to reconstruction of these often complex defects has not been described.
      The objective of this study was to establish a classification system for acquired
      vaginal defects and to develop a reconstructive algorithm derived from this
      system. This study is a retrospective review of a 7-year experience with 51 flaps
      in 37 consecutive vaginal reconstructions. Twenty-two partial defects and 15
      circumferential defects were reconstructed in 35 patients. Average patient age
      was 48 years (range, 19 to 69 years). Of the 22 patients with partial vaginal
      defects, six involved primarily the anterior and lateral wall and 16 the
      posterior vaginal wall. Among the 15 patients with circumferential defects, four
      included only the upper two-thirds of the vagina and 11 encompassed the entire
      vagina. On the basis of these defects, a classification system was developed.
      Partial defects involving the anterior or lateral vaginal wall were classified as
      type IA defects and were reconstructed primarily with pedicled Singapore
      fasciocutaneous flaps. Partial defects involving the posterior wall were
      classified as type IB and were reconstructed with pedicled rectus abdominis
      myocutaneous flaps. Circumferential defects involving the upper two-thirds of the
      vagina were classified as type IIA defects and were reconstructed with a rolled
      rectus flap or, less commonly, sigmoid colon (one patient). Total circumferential
      defects, type IIB, were reconstructed largely with bilateral gracilis flaps. Six
      patients had major complications, including one perioperative death, one complete
      flap loss, one partial flap loss, and three pelvic abscesses. Three patients had
      minor complications that included delayed wound healing and donor-site infection.
      Vaginal defects can be categorized into one of four types on the basis of the
      location and extent of resection. Flap selection is determined on the basis of
      the type of defect. Using this algorithm, immediate vaginal reconstruction with
      pedicled regional flaps can be performed with minimal patient morbidity and few
      surgical complications.

PMID- 12198419
TI  - Simultaneous GDNF and BDNF application leads to increased motoneuron survival and
      improved functional outcome in an experimental model for obstetric brachial
      plexus lesions.
AB  - Motoneurons of the neonate rat respond to proximal axonal injury with morphologic
      and functional changes and ultimately with neuronal death. Recent studies showed
      that both glial cell-line-derived neurotrophic factor (GDNF) and brain-derived
      neurotrophic factor (BDNF) reduce induced degeneration of motoneurons after
      axotomy and avulsion. Whether rescued motoneurons are functionally intact has
      been argued. In the present investigation, the authors have used a proximal crush
      lesion of the brachial plexus in neonatal rats as the experimental model of
      neuronal injury. This allowed the authors to study the effects of trophic factor
      administration on injured motoneurons and the relationship between motoneuron
      survival and extremity function. Trophic factors were locally released by small
      polymer implants in a low-dose slow-release mode. Six groups of 10 animals were
      prepared: BDNF, GDNF, GDNF/BDNF, control, sham, and normals. The number of
      surviving motoneurons was determined by retrograde tracer techniques using
      Fluorogold and Fastblue. Extremity function was quantitatively evaluated with
      functional muscle testing at day 56. The results of this study demonstrate that
      trophic factors applied separately had no effect, whereas combined trophic factor
      application (GDNF/BDNF group) had a dramatic rescue effect on motoneuron survival
      as compared with the control groups, which also effected significantly greater
      strength. The authors conclude that a combination of trophic factors leads to
      enhanced motoneuron survival, with improved voluntary function as the animal
      enters adulthood so that exogenous trophic support of motoneurons might have a
      role in the treatment of all types of severe neonatal plexopathies, maintaining
      the viability of motoneurons until reconstructive surgery provides them with a
      pathway for regeneration and endogenous trophic support.

PMID- 12198420
TI  - The dual role of perichondrium in cartilage wound healing.
AB  - Cartilage structures from the head and neck possess a certain but limited
      capacity to heal after injury. This capacity is accredited to the perichondrium.
      In this study, the role of the inner (cambium) and the outer (fibrous) layers of
      the perichondrium in cartilage wound healing in vitro is investigated. For the
      first time, the possibility of selectively removing the outer perichondrium layer
      is presented. Using rabbit ears, three different conditions were created:
      cartilage explants with both perichondrium layers intact, cartilage explants with
      only the outer perichondrium layer dissected, and cartilage explants with both
      perichondrium layers removed. The explants were studied after 0, 3, 7, 14, and 21
      days of in vitro culturing using histochemistry and immunohistochemistry for Ki
      67, collagen type II, transforming growth factor beta 1 (TGFbeta1), and
      fibroblast growth factor 2 (FGF2). When both perichondrium layers were not
      disturbed, fibrous cells grew over the cut edges of the explants from day 3 of
      culture on. New cartilage formation was never observed in this condition. When
      only the outer perichondrium layer was dissected from the cartilage explants, new
      cartilage formation was observed around the whole explant at day 21. When both
      perichondrium layers were removed, no alterations were observed at the wound
      surfaces. The growth factors TGFbeta1 and FGF2 were expressed in the entire
      perichondrium immediately after explantation. The expression gradually decreased
      with time in culture. However, the expression of TGFbeta1 remained high in the
      outer perichondrium layer and the layer of cells growing over the explant. This
      indicates a role for TGFbeta1 in the enhancement of fibrous overgrowth during the
      cartilage wound-healing process. The results of this experimental in vitro study
      demonstrate the dual role of perichondrium in cartilage wound healing. On the one
      hand, the inner layer of the perichondrium, adjacent to the cartilage, provides
      (in time) cells for new cartilage formation. On the other hand, the outer layer
      rapidly produces fibrous overgrowth, preventing the good cartilage-to-cartilage
      connection necessary to restore the mechanical function of the structure.

PMID- 12198421
TI  - Radiotherapy: effects on expanded skin.
AB  - Although the combination of radiation and tissue expansion has been associated
      with a significant rate of complications, the specific pathophysiology has yet to
      be clearly elucidated. The objective of this study was to develop a model to
      identify and examine specific histologic changes associated with tissue expansion
      and irradiation. Rectangular 50-cc silicone tissue expanders were placed
      subcutaneously over the midline dorsum of 18 adult New Zealand white rabbits.
      Preoperative radiographic dosimetry demonstrated that the radiation portal was
      away from vital intraabdominal structures. The expanders were inflated with 10 cc
      of saline every other day for a total of 80 cc. Expanders were left in place for
      2 to 3 weeks to allow fibrovascular capsule formation. The rabbits were then
      divided into three groups (six rabbits per group), each receiving one of three
      nonfractionated doses of radiation (20, 25, or 35 Gy). Half of the expanded skin
      was irradiated using a single dose, and the other half served as a nonirradiated
      control. Capsules and skin were harvested 6 weeks after the delivery of
      radiation, allowing the beginning of chronic radiation changes to occur. Using
      hematoxylin and eosin staining, histomorphometric analysis was performed. The
      data were analyzed using Student's test. Although irradiation did not affect
      dermal thickness, it did cause a statistically significant increase in epidermal
      thickness. At 20, 25, and 35 Gy the increase in epidermal thickness was 43, 90,
      and 130 percent, respectively. Although significant epidermal changes could be
      identified, capsular and dermal alterations were not evident. Further studies
      evaluating the long-term effects of alterations in capsular formation caused by
      radiation may be required.

PMID- 12198422
TI  - Unilateral cleft lip complicated by a hemangioma.

PMID- 12198423
TI  - Vascularized iliac bone flap used for sternum reconstruction after resection of
      chondrosarcoma.

PMID- 12198424
TI  - Short inframammary scar mammaplasty with an upper and lower pole-encircling skin
      resection: the bipolar technique.

PMID- 12198425
TI  - Current approach to radial nerve paralysis.
AB  - LEARNING OBJECTIVES: After studying this article, the participant should be able
      to: 1. Identify all potential points of radial nerve compression and other likely
      causes of radial nerve injury. 2. Accurately diagnose both surgical and
      nonsurgical causes of radial nerve paralysis. 3. Define a safe and effective
      approach to the surgical release and reconstruction of the radial nerve. Radial
      nerve paralysis, which can result from a complex humerus fracture, direct nerve
      trauma, compressive neuropathies, neuritis, or (rarely) from malignant tumor
      formation, has been reported throughout the literature, with some controversy
      regarding its diagnosis and management. The appropriate management of any radial
      nerve palsy depends primarily on an accurate determination of its cause,
      severity, duration, and level of involvement. The radial nerve can be injured as
      proximally as the brachial plexus or as distally as the posterior interosseous or
      radial sensory nerve. This article reviews the etiology, prognosis, and various
      treatments available for radial nerve paralysis. It also provides a new
      classification system and treatment algorithm to assist in the management of
      patients with radial nerve palsies, and it offers a simple, five-step approach to
      radial nerve release in the forearm.

PMID- 12198426
TI  - The giving tree in plastic surgery.

PMID- 12198427
TI  - Indications and use of composite grafts in 100 consecutive secondary and tertiary
      rhinoplasty patients: introduction of the axial orientation.
AB  - The fragile alar rims are complex structures whose specialized and supportive
      skin ensures the competence of the external valves and the patency of the inlets
      to the nasal airways. A chart review was performed of 100 consecutive secondary
      or tertiary rhinoplasty patients in whom the author had placed composite grafts
      before February 1999. Follow-up continued for at least 12 months. In 94 percent
      of the patients, composite grafts were harvested from the cymba conchae by
      removing the cartilage with its adherent anterior skin. In 6 percent of the
      patients, independently indicated alar wedges supplied the grafts. Six patients
      required secondary procedures to thin the alar rims, but such revisions have not
      been necessary since primary contouring of the cartilaginous graft component was
      instituted. Three auricular donor-site complications (one keloid, two thickened
      graft contours) were successfully revised through office procedures. Prior
      cosmetic rhinoplasty in a patient with normal alar cartilage anatomy exceeded all
      other etiologies as the cause of the deformity for which composite grafts were
      indicated (50 percent). The second most common etiology was deformity from prior
      rhinoplasty in a patient with alar cartilage malposition (33 percent of
      patients). Congenital deformities (7 percent of patients), trauma (6 percent),
      and prior tumor ablation (4 percent) comprised the remaining etiologies.
      Composite grafts were used most frequently to correct alar notching or asymmetry
      in rim height (43 percent of patients) or to provide an increase in apparent or
      real nasal length (28 percent). External valvular incompetence (14 percent of
      patients), nostril or vestibular stenosis (11 percent), or combined vestibular
      stenosis and lateral alar wall collapse (4 percent) were less common indications.
      Most composite grafts were oriented in the coronal plane (parallel to the alar
      rims). However, nostril or vestibular stenosis was corrected by sagittally placed
      composite grafts, and a third orientation (axial plane), to the author's
      knowledge not described previously, was used in patients with combined nostril
      stenoses and flattening of the alar walls. In this secondary rhinoplasty series,
      iatrogenic alar rim deformities or stenoses following cosmetic rhinoplasty
      dominated other causes requiring composite graft reconstruction (83 percent of
      patients). Of these 83 patients, 39.7 percent had preexisting alar cartilage
      malpositions, further supporting the importance of making accurate anatomical
      diagnosis part of every preoperative rhinoplasty plan.

PMID- 12198428
TI  - Anatomicohistologic study of the retaining ligaments of the face and use in face
      lift: retaining ligament correction and SMAS plication.
AB  - Plastic surgeons have sought to improve nasolabial folds, jowls, jaw lines, and
      cervical contour with face-lifting procedures that are abundant in the
      literature. The retaining ligaments of the face support facial soft tissue in
      normal anatomic position, resisting gravitational change. As this ligamentous
      system attenuates, facial fat descends into the plane between the superficial and
      deep facial fascia, and the stigmata of facial age develop. In this study,
      surgical correction of the retaining ligaments and plication of the superficial
      musculoaponeurotic system (SMAS) to reposition the structures that have descended
      with gravitation are discussed. The anatomy of the facial retaining ligaments was
      studied in 22 half-faces of 11 fresh cadavers, and the localization, extension,
      and width of the ligaments were examined macroscopically and histologically.
      Surgical correction of the retaining ligaments and plication of the SMAS have
      been accomplished in 27 face-lift patients with this anatomicohistologic study
      taken into consideration. There was hematoma in one patient at the cheek region
      and a permanent dimple caused by postoperative edema in two patients, with a
      localization of one zygomatic and two parotidomasseteric ligaments. In one
      patient, hypesthesia in the mandibular nerve region was seen, which remitted at
      14 weeks. There were no other complications, and with a follow-up of 24 months,
      excellent aesthetic results and a high level of patient satisfaction were
      encountered.

PMID- 12198430
TI  - A new dressing for laser-treated areas.
AB  - Contemporary studies and observations have left no doubt that occlusive dressings
      are superior to open treatment after laser resurfacing. The currently available
      occlusive dressings, however, are time-consuming to apply, often dislodge shortly
      after application, and most require reapplication. The authors report a cross
      sectional observational study of patients who were treated with a new dual
      silicone-based dressing (DiamondSeal) after full-face laser resurfacing, with or
      without rhytidectomy. Patients who previously underwent similar surgeries and who
      were treated with a popular occlusive tape dressing (Flexzan) acted as historic
      controls. A combination of two silicones produced a gel-like silicone admixture
      that was spread evenly over the laser-treated areas. The silicone gel solidified
      into a flexible membrane and remained on the patient's face for 5 days.
      Questionnaires were sent to patients who were treated with the silicone dressing
      and those who were treated with a currently popular occlusive dressing. When the
      attributes of these dressings were compared, the superiority of the silicone
      dressing approached statistical significance ( = 0.08). The majority of patients
      treated with the silicone dressing (71 percent) had a positive experience with
      this dressing, stating they would repeat the experience if necessary. Only 54
      percent of patients with a tape dressing were willing to repeat their experience
      ( = 0.18). The major advantages of this dressing, noted from the surgeon's
      perspective, were the speed with which the mask was applied; the ease of
      application, without the need for templates; the acceptable cure duration,
      allowing spontaneous contouring of the silicone along facial contours; the simple
      tailoring of the dressing; the reduced need for and minimal time for
      reapplication; and the paucity of complications.

PMID- 12198431
TI  - Laboratory and histopathologic comparative study of internal ultrasound-assisted
      lipoplasty and tumescent lipoplasty.
AB  - Despite the advantages of using internal ultrasound-assisted lipoplasty instead
      of the classic tumescent lipoplasty, such as reduced bleeding and tissue damage,
      the authors found no objective or comparative study of these techniques in
      humans. For this reason, they conducted a clinical study to determine the amount
      of bleeding and tissue damage caused by each of the techniques. A simple clinical
      assay was accomplished at the Jalisco Plastic Surgery Institute on seven female
      patients scheduled for abdominal lipectomy. Two similar sections of the surgical
      area were marked for lipoplasty techniques: classic tumescent lipoplasty on one
      side and internal ultrasound-assisted lipoplasty on the other. Both areas were
      treated simultaneously by surgeons experienced in each technique. Laboratory
      tests and histologic studies were performed on the aspirated material and the
      manipulated tissue, respectively. The fluids sent to the laboratory were analyzed
      to determine the amount of bleeding and tissue damage. In the laboratory, the
      degree of lesion and tissue damage was evaluated in the dermis, nerves, blood
      vessels, and adipose cells. With internal ultrasound-assisted lipoplasty,
      indicators of tissue damage such as glutamic oxalacetic transaminase, pyruvic
      oxalacetic transaminase, cholinesterase, and myoglobin showed higher values than
      with tumescent lipoplasty. The same was found for hemoglobin levels and in the
      histologic data indicative of tissue damage; both values were statistically
      significant at < 0.001. Internal ultrasound-assisted lipoplasty was not
      demonstrated to be more innocuous or to have a selective effect in adipose cells,
      and it generally resulted in more tissue damage and bleeding than the classic
      tumescent technique.

PMID- 12198435
TI  - Health care isn't for everybody.

PMID- 12198434
TI  - Apollo revisited, revisited.

PMID- 12198433
TI  - Gonzalez-Ulloa's Manifesto on aesthetic surgery.
AB  - The realization that the proper development of aesthetic surgery was hindered by
      a bias against such practice by departmental heads and editors of medical
      journals led Dr. Mario Gonzalez-Ulloa from Mexico to formulate a "Manifesto" on
      this speciality in the 1960s. This Manifesto has been of utmost importance to our
      speciality because it served to disseminate responsible opinion concerning
      aesthetic surgery among specialists. Although the bare text of the Manifesto was
      published in 1966, its content has so far been lost to future generations of
      plastic surgeons. Because its place in the history of aesthetic plastic surgery
      needs to be acknowledged, Gonzalez-Ulloa's Manifesto is presented and discussed
      here.

PMID- 12198436
TI  - Hydroxyapatite.

PMID- 12198437
TI  - Comments regarding NLite.

PMID- 12198439
TI  - Another practical method for arm restraint in children with cleft lip/palate.

PMID- 12198440
TI  - Neurothekeoma in a burned extremity.

PMID- 12198442
TI  - Significance of residual tumor cells after re-excision of incompletely excised
      basal cell carcinomas.

PMID- 12198441
TI  - Superior ulnar collateral artery or superficial ulnar artery: does it make a
      difference?

PMID- 12198443
TI  - Simple methods of preventing microvascular free flap failure.

PMID- 12198444
TI  - The multipurpose syringe: finger splints.

PMID- 12198445
TI  - The role of tissue expansion in the management of large congenital pigmented nevi
      of the forehead in the pediatric patient.

PMID- 12198447
TI  - Early return to normal activities after breast augmentation.

PMID- 12198446
TI  - Chronic facial edema caused by multiple bee stings: effective treatment with
      liposuction.

PMID- 12198448
TI  - Pseudofolliculitis of the neck and the shoulder: a new effective treatment with
      alexandrite laser.

PMID- 12198449
TI  - Radial forearm osteocutaneous flap for mandibular reconstruction.

PMID- 12198450
TI  - Squamous carcinoma arising from chronic pilonidal disease.

PMID- 12198451
TI  - Dual plane breast augmentation: avoiding pectoralis major displacement.

PMID- 12198452
TI  - A critical analysis of the Roelfsema and Cobben severity score in EEC syndrome.

PMID- 12198453
TI  - Prefabrication of thin flap using fascia.

PMID- 12198454
TI  - Textured silicone breast implants.

PMID- 12198455
TI  - Muscle-based gene therapy and tissue engineering for treatment of growth plate
      injuries.
AB  - Growth plate injuries may lead to a progressive angular deformity or longitudinal
      growth disturbance. The authors investigated the feasibility of gene therapy and
      tissue engineering based on autologous muscle-and adenoviral-mediated gene
      transfer of insulin-like growth factor-1 (IGF-1) and bone morphogenetic protein-2
      (BMP-2) to treat tibial physeal defects in rabbits. The medial half of the left
      proximal tibial growth plate was completely excised in 44 6-week-old New Zealand
      white rabbits. Four experimental groups were created: no treatment (I),
      autologous muscle interposition (II), autologous muscle interposition injected
      with adIGF-1 (III), and autologous muscle interposition injected with adBMP-2
      (IV). Radiographic and histologic assessments were obtained postoperatively.
      Significant tibial shortening and a compact osseous bridge were observed in
      groups I and IV. Growth plates remained open in groups II and III. This
      experiment demonstrates that IGF-1 had a supportive effect on physeal
      chondrocytes, while BMP-2 caused increased osteogenic activity in the injured
      growth plates.

PMID- 12198456
TI  - Role of magnetic resonance imaging in the assessment of pediatric cervical spine
      injuries.
AB  - The purpose of this study was to determine the role of magnetic resonance imaging
      (MRI) in the evaluation of children with suspected cervical spine injury (CSI).
      The authors studied 237 consecutive children, 74 of whom were evaluated by MRI
      based on a trauma protocol of the authors' institution. The criteria for MRI
      were: (1) an obtunded or nonverbal child suspected of having CSI, (2) equivocal
      plain films, (3) neurologic symptoms without radiographic findings, or (4) an
      inability to clear the cervical spine within 3 days, based on testing. The
      average age of the evaluated children was 8 years. MRI confirmed the plain
      radiography diagnosis in 66% of children and altered the diagnosis in 34%. MRI is
      valuable in the evaluation of potential CSI, especially in obtunded children or
      children with equivocal plain radiographs.

PMID- 12198457
TI  - Definition of two types of anterior superior iliac spine avulsion fractures.
AB  - Fractures of the anterior superior iliac spine (ASIS) in adolescents are usually
      due to avulsion of the sartorius origin from the ASIS; however, the authors here
      report a second type due to avulsion of the tensor fascia lata origin. Eight
      patients were identified with ASIS avulsion fractures. Type II sartorius avulsion
      fracture was due to sprinting in various sports (n = 6). The fragment was smaller
      and displaced anteriorly. Type II tensor fascia lata avulsion fractures were due
      to swinging a baseball bat. The two muscular males were both injured during the
      initial phase of batting. The bony fragment was much larger and displaced
      laterally as confirmed by three-dimensional computed tomography scans.

PMID- 12198458
TI  - Chronic radial head dislocation in children, Part 1: pathologic changes
      preventing stable reduction and surgical correction.
AB  - The pathologic changes in 15 elbows of 14 children (2 bilateral congenital, 12
      unilateral posttraumatic, mean age 9.5 years) with radial head dislocation
      unreduced for at least 3 months (range 3-180 months) and their open treatment
      were reviewed. Common dysplastic changes observed in both congenital and
      posttraumatic groups included large deformed radial heads, slender radial necks,
      and ulnar bowing. Changes were bilateral and symmetrical in the congenital group.
      In traumatic dislocations, patients with more severe deformities had longer
      delays from time of injury to time of reduction. Persistent pain, limitation of
      motion, and deformity were unacceptable symptoms to both patients and their
      parents, prompting surgical intervention. To produce a smooth rotational arc for
      the radius and maintain it in stable reduction, restoration of the congruency of
      the capitello-radioulnar joint and correction of the various dysplastic changes
      were mandatory during open reduction.

PMID- 12198459
TI  - Chronic radial head dislocation in children, Part 2: results of open treatment
      and factors affecting final outcome.
AB  - Fifteen elbows (3 congenital, 12 traumatic) in 14 children (mean age 9.5 years)
      with chronic radial head dislocation for at least 3 months (range 3-180 months)
      underwent radial head-sparing reconstructive surgery and were followed up at an
      average of 43.5 months postoperatively (range 12-105 months). At follow-up, the
      patients were evaluated radiographically and clinically using range-of-motion
      measurements and an elbow performance score based on four parameters (deformity,
      pain, motion, function). Ten cases had excellent results, two had good results,
      two had fair results, and one case had poor results. Scores at follow-up were
      evaluated with seven preoperative factors. Among those, the degree of
      preoperative carrying angle asymmetry associated with flexion contracture
      correlated significantly with the elbow scores. The most common complication was
      loss of pronation. The authors advocate radial head reduction and reconstruction
      in chronic radial head dislocations in children after obtaining informed consent
      from patient and parents.

PMID- 12198460
TI  - Surgical treatment of posttraumatic radioulnar synostosis in children.
AB  - The authors describe two children who underwent surgical treatment of radioulnar
      synostosis. One case involved simple excision; the other, excision and
      interposition of Gore-Tex vascular graft material. In a review of the literature,
      no other report of the latter type of surgical treatment was found. A discussion
      of the literature concerning this rare complication in children and the current
      surgical treatment options are included.

PMID- 12198461
TI  - Femoral head deformity in Catterall groups III and IV Legg-Calve-Perthes disease:
      magnetic resonance image analysis in coronal and sagittal planes.
AB  - The authors investigated the deformity of the cartilaginous femoral head in 30
      patients who had unilaterally affected Catterall groups III and IV Legg-Calve
      Perthes disease. The extent of collapse and the sphericity of cartilaginous head
      were determined using coronal and sagittal magnetic resonance images. The maximal
      femoral head collapse was larger in the sagittal plane than in the coronal plane;
      however, the instant radii of curvature varied significantly more in the coronal
      plane than in the sagittal plane. These data suggest that the sphericity of the
      femoral head is better maintained, despite a more extensive collapse, in the
      sagittal plane. The authors assume that the physiologic, wider range of hip
      motion in the sagittal plane in daily life helps to maintain the sphericity of
      the femoral head in the sagittal plane by a molding mechanism. These observations
      support the current concept of containment and motion therapy.

PMID- 12198462
TI  - Natural history of hips with borderline acetabular index and acetabular dysplasia
      in infants.
AB  - Management of clinically stable hips with an increased age-related acetabular
      index (AI) remains controversial. The authors' purpose was to document the
      natural history of such hips. Sixty-eight clinically stable hips with an
      increased age-related AI were followed up for a mean of 9.5 years. Four patterns
      of evolution were observed: type 1 (25 hips) had rapid progression to normal
      range in the first 2 years; type 2 (19 hips) had slow improvement, with AI values
      reaching the normal range between 4 and 11 years; type 3 (20 hips) had improved
      hip morphology with persistence of minor deviations from the normal values; and
      type 4 (4 hips) showed no improvement. Initially, none of the hips with type 1,
      2, or 3 pattern showed radiologic signs of displacement; in contrast, all our
      type 4 hips were radiologically eccentered. Clinically stable and radiologically
      well-centered hips with an increased age-related AI improved spontaneously
      without treatment. For these cases, clinical and radiologic follow-up is all that
      is needed.

PMID- 12198463
TI  - Three-year prospective study of developmental dysplasia of the hip at birth:
      should all dislocated or dislocatable hips be treated?
AB  - This article presents a 3-year prospective study that includes 103 consecutive
      patients (137 hips) diagnosed with developmental dysplasia of the hip (DDH) at
      birth. Treatment was started after 2 weeks only if the hips had not stabilized
      spontaneously. Sonographic studies were first used when clinical stability was
      confirmed to ensure a true concentric hip reduction. The authors conclude that
      most patients with DDH at birth (73.8%) do not need treatment at that time,
      presenting with normal hips at the end of follow-up. When instability was still
      present after 2 weeks and a splint was applied (26.2%), there were no significant
      hip differences when compared with a control group of 50 patients (69 hips) who
      underwent treatment in the first days of life. With this approach, the authors
      could safely reduce the number of patients to be treated, the amount of
      sonographic studies, and consequently the final cost of the whole treatment.

PMID- 12198464
TI  - Acetabular protrusion in osteogenesis imperfecta.
AB  - The charts and radiographs of 79 patients with osteogenesis imperfecta (OI)
      actively followed at the authors' institution were reviewed to determine the
      incidence of acetabular protrusion (AP) in OI and to evaluate the clinical
      consequences of this pelvic deformity. All 79 patients had iliac crest bone
      biopsy and pelvic radiographs. They were subdivided into OI type 1, 3, and 4,
      according to the Sillence classification, and type 5, according to Glorieux. AP
      was measured on pelvic radiographs, using the center-edge angle of Wiberg and the
      acetabular ilioischial line. Twenty-six patients (33%) had radiologic evidence of
      AP, with the highest incidence in OI type 3 (69%) and OI type 5 (54%). Only 3 of
      these 24 patients (13%) had medical problems that could be related to AP: severe
      constipation and hip ankylosis. The authors conclude that in this series of 79
      patients with OI, AP is not uncommon and in rare cases may lead to severe medical
      complications.

PMID- 12198465
TI  - Deformity correction of knee and leg lengthening by Ilizarov method in
      hypophosphatemic rickets: outcomes and significance of serum phosphate level.
AB  - The authors evaluated 14 patients with hypophosphatemic rickets who underwent
      correction of a knee deformity along with a leg lengthening by the Ilizarov
      method. Deformity correction alone was performed in 8 femora and 4 tibiae
      fibulae, and concomitant deformity correction and limb lengthening (>1.0 cm) in 9
      femora and 19 tibiae-fibulae. The healing index correlated with the biochemical
      parameters. Knee deformities were satisfactorily corrected in all patients except
      one. There was a statistically significant negative correlation between the
      healing index and the serum phosphate level: those who had a serum phosphate
      level higher than 2.5 mg/dL showed a relatively rapid regenerate bone healing
      compared with those with less than 2.5 mg/dL. The authors conclude that a serum
      phosphate level of 2.5 mg/dL as a cut-off point should be considered in deciding
      whether deformity correction alone or with a concomitant leg lengthening should
      be undertaken.

PMID- 12198466
TI  - Management of childhood chronic tibial osteomyelitis with the Ilizarov method.
AB  - The efficacy of the Ilizarov method in the management of the long bone defect is
      well established. There have been rare reports about the use of the Ilizarov
      method in the bone defect caused from childhood osteomyelitis. In this article,
      the authors present results of seven patients with childhood chronic hematogenous
      osteomyelitis of the tibia who were treated with the Ilizarov method. The
      treatment protocol also included sequestrectomy and debridement, appropriate
      antibiotic therapy, and bifocal treatment with the Ilizarov method. The mean age
      was 7.2 years old (range 6-8). After sequestrectomy and debridement, all cases
      were classified as B1 infected pseudoarthrosis according to Paley's criteria. All
      patients had active infection at the beginning of the treatment. The mean bone
      defect was 7.4 cm (range 3.5-12). Follow-up time was 4.6 years (range 2.7-5.8).
      At the time of fixator extraction, complete consolidation was obtained in all the
      patients. Healing index was 32.3 days/cm (range 28-44). Bone grafting was not
      required at the docking site in any of the patients. Functional and radiologic
      results were judged excellent according to Paley's criteria in all patients at
      the last follow-up. This study indicates that the bifocal method of the Ilizarov
      treatment is the best alternative for the bone defect caused by chronic
      hematogenous osteomyelitis in children.

PMID- 12198467
TI  - Recurrence of varus deformity after proximal tibial osteotomy in Blount disease:
      long-term follow-up.
AB  - In a retrospective review of 74 tibial osteotomies performed for Blount disease,
      the patients were divided into three groups based on age and treatment. Group A
      (26 osteotomies), 4 years old or younger, and group B (34 osteotomies), older
      than 4 years, were treated the same with osteotomy and crossed pins. Group C (14
      osteotomies), older than 4 years, was treated with osteotomy and external
      fixator. At 6 years of follow-up, the recurrence of varus deformity was 46%, 94%,
      and 72% in groups A, B, and C, respectively. There was no correlation between
      recurrence of varus deformity and preoperative deformity angle or degree of
      surgical correction. Fixation with crossed pins or external fixator was not a
      factor. Surgery at 4 years old or younger and correction of the postoperative
      deformity angle in valgus may obviate recurrence of varus deformity in Blount
      disease at long-term follow-up.

PMID- 12198468
TI  - Complications of tibial osteotomies in children with comorbidities.
AB  - Tibial osteotomies in children have been associated with a number of
      complications. A retrospective review of 116 children who had 129 tibial
      osteotomies was performed to assess these complications at our institution.
      Results showed that there were 35 cases of wound problems, 6 cases of
      recurrence/reoperation, 5 cases of delayed union, 2 cases with transient peroneal
      nerve palsy, 1 case of nonunion, and 1 case of mal-union. Patients having certain
      comorbidities had a higher frequency of complications. There were no significant
      differences between the location of the tibial osteotomy (proximal or distal) and
      the incidence of complication. External fixation was associated with a lower
      incidence of complications than the use of pins and casting. Although our results
      demonstrate an overall low complication rate, there is a significant association
      between complications and comorbid conditions. This highlights the need to
      recognize comorbidities preoperatively and the potential of increased
      postoperative complications.

PMID- 12198469
TI  - Radiographic assessment of bone formation in tibia during distraction
      osteogenesis.
AB  - The radiologic appearance of bone formation during limb lengthening is used to
      judge the competence of the underlying biologic process and predict the likely
      time to healing. Interpretation is, however, based upon subjective parameters
      that have never been clearly defined. Thirty anteroposterior radiographs from
      pediatric tibial lengthenings were classified by four pairs of surgeons using a
      three-part system. Across the group, interobserver consistency showed
      considerable variation for all parameters tested. Pairwise analysis indicated
      that the surgeons directly involved in limb lengthening procedures agreed better
      than those whose practice was of a different nature. A second series of
      radiographs contained 12 radiographs with a satisfactory and 12 with a poor bone
      healing index (BHI). These radiographs were digitized, and an interobserver study
      showed significantly improved observer concordance if the images were enhanced.
      No feature was associated with a 100% chance of a satisfactory outcome, but
      certain appearances in the regenerate were associated with a better BHI than
      others.

PMID- 12198470
TI  - Physiologic weight-bearing and consolidation of new bone in a rat model of
      distraction osteogenesis.
AB  - To evaluate the effect of weight-bearing on consolidation of the regenerate in
      distraction osteogenesis, unilateral femoral lengthenings were performed in two
      groups of rats. In the first group (n = 19) unrestricted weight-bearing was
      permitted postoperatively, while in the second (n = 18) weight-bearing was
      prevented via a through-knee amputation. In both groups the distraction protocol
      involved a 3-day latency period, four daily 0.5-mm lengthenings, and 35 days of
      consolidation. Healing was evaluated with serial radiographs (days 0, 7, 14, 28,
      and 35) and at sacrifice with measurement of ash weight, quantitative histology,
      and mechanical testing. Histomorphometry revealed that the callus in the weight
      bearing animals was significantly larger than in the non-weight-bearing animals,
      primarily due to increases in periosteal and interzone new bone; there was no
      significant increase in cartilage formation. Weight-bearing had no significant
      effect on the stiffness, strength, or mineral content of the regenerate. These
      findings suggest that weight-bearing may be capable of influencing consolidation
      of the regenerate in distraction osteogenesis. Additional studies will be
      required to determine the optimal loading for new bone formation.

PMID- 12198471
TI  - Hip displacement in spastic cerebral palsy: repeatability of radiologic
      measurement.
AB  - Radiologic measures of migration percentage (MP) and acetabular index (AI) taken
      from plain radiographs of the pelvis are the most commonly used tools for
      determining hip displacement and management options in children with cerebral
      palsy and spastic hip disease. This study determined interrater and intrarater
      reliability of MP and AI on pelvic radiographs chosen to represent a wide range
      of age (11 months to 8 years 5 months), MP (0%-56%), and AI (9 degrees -33
      degrees ). The study demonstrated that an experienced rater would be expected to
      measure MP on a single radiograph to within +/-5.8% of the true value and a
      change in MP between two radiographs taken at different times to within +/-8.3%
      of the true value. Similarly for AI, the measurement error for a typical rater
      would be within +/-2.6 degrees on a single reading and +/-3.7 degrees if
      recording change between two occasions. The authors believe that the results
      indicating true change are acceptable in clinical practice, provided treatment
      decisions are based on a series of radiographs taken at 6-month intervals,
      methods and training are standardized, and consistent raters are used.

PMID- 12198472
TI  - Untreated hip dislocation in cerebral palsy.
AB  - The purpose of this study was to evaluate the problems associated with hip
      dislocation in adults with cerebral palsy. Twenty-nine subjects with dislocated
      hips and no prior hip surgery were identified. There were a total of 38
      dislocated hips. Age range was 21 to 52 years (average 34). Seven dislocated hips
      (18%) were definitely painful and four hips (11%) produced only mild or
      intermittent pain. Twenty-seven hips (71%) were not painful. The seven painful
      hips underwent proximal femoral resection, resulting in excellent range of motion
      and no pain. In conclusion, for established nonpainful hip dislocation in the
      severely involved spastic quadriplegic patient, aggressive surgical treatment
      should be undertaken only after careful consideration of the natural history. If
      a dislocated hip becomes painful in adulthood or develops an adduction
      contracture interfering with perineal care, a proximal femoral resection can be
      performed with reliably good success.

PMID- 12198473
TI  - Rectus and hamstring surgery in cerebral palsy: a gait analysis study of results
      by functional ambulation level.
AB  - The purpose of this study is to determine if children more severely involved with
      cerebral palsy respond as well to rectus transfer and hamstring surgery as those
      with less severe involvement. Ninety-nine children were classified as independent
      community ambulators, crutch/walker-dependent community ambulators, or
      household/exercise ambulators. Maximum knee extension in stance and total range
      of knee motion in gait increased following surgery in all groups. Peak knee
      flexion in swing was maintained in the independent group only, but timing of knee
      flexion in swing improved in all groups. All groups showed increases in stride
      length, and the household/exercise group also showed an increase in walking
      speed. Four of 39 crutch/walker-dependent community ambulators and 13 of 21
      household/exercise ambulators progressed to the next higher functional ambulation
      group.

PMID- 12198474
TI  - Natural progression of gait in children with cerebral palsy.
AB  - Twenty-eight children with cerebral palsy had two gait analyses an average of 4.4
      years apart with no surgical intervention between the tests. The effects of
      growth and age were examined using three-dimensional kinematics, temporal and
      stride parameters, and clinical examination measures. Kinematic changes showed
      decreases in hip, knee, and ankle sagittal plane ranges of motion (ROM), peak hip
      flexion in swing, and peak knee flexion over time. Temporal and stride parameters
      showed declines in timing of toe off, cadence, and walking velocity. Clinical
      measures showed declines in hip abduction ROM (knees flexed and extended),
      popliteal angle, and sagittal plane ankle ROM (knees flexed and extended).
      Overall results showed that gait function in these individuals with cerebral
      palsy decreased longitudinally with respect to temporal/stride measures, passive
      ROM, and kinematic parameters compared with a group of individuals who had had
      orthopaedic intervention.

PMID- 12198475
TI  - Neurologic risk management in scoliosis surgery.

PMID- 12198476
TI  - Clinical analysis of short stature.

PMID- 12198477
TI  - Fracture stability after pinning of displaced supracondylar distal humerus
      fractures in children.

PMID- 12198481
TI  - TAGging the target for damage control.

PMID- 12198480
TI  - Retaining your identity under stress.

PMID- 12198482
TI  - Chaperones and transcriptional regulation by nuclear receptors.

PMID- 12198483
TI  - A P-type ion pump at work.

PMID- 12198484
TI  - Picture story. Double, double coils or trouble.

PMID- 12198485
TI  - Molecular dynamics simulations of biomolecules.
AB  - Molecular dynamics simulations are important tools for understanding the physical
      basis of the structure and function of biological macromolecules. The early view
      of proteins as relatively rigid structures has been replaced by a dynamic model
      in which the internal motions and resulting conformational changes play an
      essential role in their function. This review presents a brief description of the
      origin and early uses of biomolecular simulations. It then outlines some recent
      studies that illustrate the utility of such simulations and closes with a
      discussion of their ever-increasing potential for contributing to biology.

PMID- 12198486
TI  - Cellvibrio japonicus alpha-L-arabinanase 43A has a novel five-blade beta
      propeller fold.
AB  - Cellvibrio japonicus arabinanase Arb43A hydrolyzes the alpha-1,5-linked L
      arabinofuranoside backbone of plant cell wall arabinans. The three-dimensional
      structure of Arb43A, determined at 1.9 A resolution, reveals a five-bladed beta
      propeller fold. Arb43A is the first enzyme known to display this topology. A long
      V-shaped surface groove, partially enclosed at one end, forms a single extended
      substrate-binding surface across the face of the propeller. Three carboxylates
      deep in the active site groove provide the general acid and base components for
      glycosidic bond hydrolysis with inversion of anomeric configuration.

PMID- 12198487
TI  - DNA binding is required for the apoptogenic action of apoptosis inducing factor.
AB  - The execution of apoptosis or programmed cell death comprises both caspase
      dependent and caspase-independent processes. Apoptosis inducing factor (AIF) was
      identified as a major player in caspase-independent cell death. It induces
      chromatin condensation and initial DNA cleavage via an unknown molecular
      mechanism. Here we report the crystal structure of human AIF at 1.8 A resolution.
      The structure reveals the presence of a strong positive electrostatic potential
      at the AIF surface, although the calculated isoelectric point for the entire
      protein is neutral. We show that recombinant AIF interacts with DNA in a sequence
      independent manner. In addition, in cells treated with an apoptotic stimulus,
      endogenous AIF becomes co-localized with DNA at an early stage of nuclear
      morphological changes. Structure-based mutagenesis shows that DNA-binding
      defective mutants of AIF fail to induce cell death while retaining nuclear
      translocation. The potential DNA-binding site identified from mutagenesis also
      coincides with computational docking of a DNA duplex. These observations suggest
      that AIF-induced nuclear apoptosis requires a direct interaction with DNA.

PMID- 12198488
TI  - The structural basis for specificity in human ABO(H) blood group biosynthesis.
AB  - The human ABO(H) blood group antigens are produced by specific
      glycosyltransferase enzymes. An N-acetylgalactosaminyltransferase (GTA) uses a
      UDP-GalNAc donor to convert the H-antigen acceptor to the A antigen, whereas a
      galactosyltransferase (GTB) uses a UDP-galactose donor to convert the H-antigen
      acceptor to the B antigen. GTA and GTB differ only in the identity of four
      critical amino acid residues. Crystal structures at 1.8-1.32 A resolution of the
      GTA and GTB enzymes both free and in complex with disaccharide H-antigen acceptor
      and UDP reveal the basis for donor and acceptor specificity and show that only
      two of the critical amino acid residues are positioned to contact donor or
      acceptor substrates. Given the need for stringent stereo- and regioselectivity in
      this biosynthesis, these structures further demonstrate that the ability of the
      two enzymes to distinguish between the A and B donors is largely determined by a
      single amino acid residue.

PMID- 12198491
TI  - Lon protease preferentially degrades oxidized mitochondrial aconitase by an ATP
      stimulated mechanism.
AB  - Mitochondrial aconitase is sensitive to oxidative inactivation and can aggregate
      and accumulate in many age-related disorders. Here we report that Lon protease,
      an ATP-stimulated mitochondrial matrix protein, selectively recognizes and
      degrades the oxidized, hydrophobic form of aconitase after mild oxidative
      modification, but that severe oxidation results in aconitase aggregation, which
      makes it a poor substrate for Lon. Similarly, a morpholino oligodeoxynucleotide
      directed against the lon gene markedly decreases the amount of Lon protein, Lon
      activity and aconitase degradation in WI-38 VA-13 human lung fibroblasts and
      causes accumulation of oxidatively modified aconitase. The ATP-stimulated Lon
      protease may be an essential defence against the stress of life in an oxygen
      environment. By recognizing minor oxidative changes to protein structure and
      rapidly degrading the mildly modified protein, Lon protease may prevent extensive
      oxidation, aggregation and accumulation of aconitase, which could otherwise
      compromise mitochondrial function and cellular viability. Aconitase is probably
      only one of many mitochondrial matrix proteins that are preferentially degraded
      by Lon protease after oxidative modification.

PMID- 12198492
TI  - Imaging actin and dynamin recruitment during invagination of single clathrin
      coated pits.
AB  - As a final step in endocytosis, clathrin-coated pits must separate from the
      plasma membrane and move into the cytosol as a coated vesicle. Because these
      events involve minute movements that conventional light microscopy cannot
      resolve, they have not been observed directly and their dynamics remain
      unexplored. Here, we used evanescent field (EF) microscopy to observe single
      clathrin-coated pits or vesicles as they draw inwards from the plasma membrane
      and finally lose their coats. This inward movement occurred immediately after a
      brief burst of dynamin recruitment and was accompanied by transient actin
      assembly. Therefore, dynamin may provide the trigger and actin may provide the
      force for movement into the cytosol.

PMID- 12198493
TI  - Filamin is essential in actin cytoskeletal assembly mediated by p21-activated
      kinase 1.
AB  - The serine/threonine kinase p21-activated kinase 1 (Pak1) controls the actin
      cytoskeletal and ruffle formation through mechanisms that are independent of
      GTPase activity. Here we identify filamin FLNa as a Pak1-interacting protein
      through a yeast two-hybrid screen using the amino terminus of Pak1 as a bait.
      FLNa is stimulated by physiological signalling molecules to undergo
      phosphorylation by Pak1 and to interact and colocalize with endogenous Pak1 in
      membrane ruffles. The ruffle-forming activity of Pak1 is functional in FLNa
      expressing cells but not in FLNa-deficient cells. In FLNa, the Pak1-binding site
      involves tandem repeat 23 in the carboxyl terminus and phosphorylation takes
      place on serine 2152. The FLNa-binding site in Pak1 is localized between amino
      acids 52 and 132 in the conserved Cdc42/Rac-interacting (CRIB) domain;
      accordingly, FLNa binding to the CRIB domain stimulates Pak1 kinase activity. Our
      results indicate that FLNa may be essential for Pak1-induced cytoskeletal
      reorganization and that the two-way regulatory interaction between Pak1 and FLNa
      may contribute to the local stimulation of Pak1 activity and its targets in
      cytoskeletal structures.

PMID- 12198494
TI  - Microscopic analysis of polymerization dynamics with individual actin filaments.
AB  - The polymerization-depolymerization dynamics of actin is a key process in a
      variety of cellular functions. Many spectroscopic studies have been performed in
      solution, but studies on single actin filaments have just begun. Here, we show
      that the time course of polymerization of individual filaments consists of a
      polymerization phase and a subsequent steady-state phase. During the steady-state
      phase, a treadmilling process of elongation at the barbed end and shortening at
      the pointed end occurs, in which both components of the process proceed at
      approximately the same rate. The time correlation of length fluctuation of the
      filaments in the steady-state phase showed that the polymerization
      depolymerization dynamics follow a diffusion (stochastic) process, which cannot
      be explained by simple association and dissociation of monomers at both ends of
      the filaments.

PMID- 12198495
TI  - Reaper-mediated inhibition of DIAP1-induced DTRAF1 degradation results in
      activation of JNK in Drosophila.
AB  - Although Jun amino-terminal kinase (JNK) is known to mediate a physiological
      stress signal that leads to cell death, the exact role of the JNK pathway in the
      mechanisms underlying intrinsic cell death is largely unknown. Here we show
      through a genetic screen that a mutant of Drosophila melanogaster tumour-necrosis
      factor receptor-associated factor 1 (DTRAF1) is a dominant suppressor of Reaper
      induced cell death. We show that Reaper modulates the JNK pathway through
      Drosophila inhibitor-of-apoptosis protein 1 (DIAP1), which negatively regulates
      DTRAF1 by proteasome-mediated degradation. Reduction of JNK signals rescues the
      Reaper-induced small eye phenotype, and overexpression of DTRAF1 activates the
      Drosophila ASK1 (apoptosis signal-regulating kinase 1; a mitogen-activated
      protein kinase kinase kinase) and JNK pathway, thereby inducing cell death.
      Overexpresson of DIAP1 facilitates degradation of DTRAF1 in a ubiquitin-dependent
      manner and simultaneously inhibits activation of JNK. Expression of Reaper leads
      to a loss of DIAP1 inhibition of DTRAF1-mediated JNK activation in Drosophila
      cells. Taken together, our results indicate that DIAP1 may modulate cell death by
      regulating JNK activation through a ubiquitin#150;proteasome pathway.

PMID- 12198496
TI  - The semaphorin 4D receptor controls invasive growth by coupling with Met.
AB  - Semaphorins are cell surface and soluble signals that control axonal guidance.
      Recently, semaphorin receptors (plexins) have been discovered and shown to be
      widely expressed. Their biological activities outside the nervous system and the
      signal transduction mechanism(s) they utilize are largely unknown. Here, we show
      that in epithelial cells, Semaphorin 4D (Sema 4D) triggers invasive growth, a
      complex programme that includes cell#150;cell dissociation, anchorage-independent
      growth and branching morphogenesis. Interestingly, the same response is also
      controlled by scatter factors through their tyrosine kinase receptors, which
      share striking structural homology with plexins in their extracellular domain. We
      found that in cells expressing the endogenous proteins, Plexin B1 (the Sema 4D
      Receptor) and Met (the Scatter Factor 1/ Hepatocyte Growth Factor Receptor)
      associate in a complex. In addition, binding of Sema 4D to Plexin B1 stimulates
      the tyrosine kinase activity of Met, resulting in tyrosine phosphorylation of
      both receptors. Finally, cells lacking Met expression do not respond to Sema 4D
      unless exogenous Met is expressed. This work identifies a novel biological
      function of semaphorins and suggests the involvement of an unexpected signalling
      mechanism, namely, the coupling of a plexin to a tyrosine kinase receptor.

PMID- 12198497
TI  - MOR1/GEM1 has an essential role in the plant-specific cytokinetic phragmoplast.
AB  - MOR1 is a member of the MAP215 family of microtubule-associated proteins and is
      required to establish interphase arrays of cortical microtubules in plant cells.
      Here we show that MOR1 binds microtubules in vivo, localizing to both cortical
      microtubules and to areas of overlapping microtubules in the phragmoplast.
      Genetic complementation of the cytokinesis-defective gemini pollen 1-1 (gem1-1)
      mutation with MOR1 shows that MOR1 (which is synonymous with the protein GEM1) is
      essential in cytokinesis. Phenotypic analysis of gem1-1 and gem1-2, which
      contains a T-DNA insertion, confirm that MOR1/GEM1 is essential for regular
      patterns of cytokinesis. Both the gem1-1 and gem1-2 mutations cause the
      truncation of the MOR1/GEM1 protein. In addition, the carboxy-terminal domain of
      the protein, which is absent in both mutants, binds microtubules in vitro. Our
      data show that MOR1/GEM1 has an essential role in the cytokinetic phragmoplast.

PMID- 12198498
TI  - Proteasome subunit Rpn1 binds ubiquitin-like protein domains.
AB  - The yeast protein Rad23 belongs to a diverse family of proteins that contain an
      amino-terminal ubiquitin-like (UBL) domain. This domain mediates the binding of
      Rad23 to proteasomes, which in turn promotes DNA repair and modulates protein
      degradation, possibly by delivering ubiquitinylated cargo to proteasomes. Here we
      show that Rad23 binds proteasomes by directly interacting with the base
      subcomplex of the regulatory particle of the proteasome. A component of the base,
      Rpn1, specifically recognizes the UBL domain of Rad23 through its leucine-rich
      repeat-like (LRR-like) domain. A second UBL protein, Dsk2, competes with Rad23
      for proteasome binding, which suggests that the LRR-like domain of Rpn1 may
      participate in the recognition of several ligands of the proteasome. We propose
      that the LRR domain of Rpn1 may be positioned in the base to allow the cargo
      proteins carried by Rad23 to be presented to the proteasomal ATPases for
      unfolding. We also report that, contrary to expectation, the base subunit Rpn10
      does not mediate the binding of UBL proteins to the proteasome in yeast, although
      it can apparently contribute to the binding of ubiquitin chains by intact
      proteasomes.

PMID- 12198499
TI  - Subnuclear shuttling of human telomerase induced by transformation and DNA
      damage.
AB  - The telomerase ribonucleoprotein complex caps chromosome ends by adding telomeric
      repeats. Here we show that catalytically active human telomerase has a regulated
      intranuclear localization that is dependent on the cell-cycle stage,
      transformation and DNA damage. In primary cell lines, low expression of a fusion
      protein of green fluorescent protein and telomerase reverse transcriptase (GFP
      hTERT) increases telomerase activity and stabilizes the maintenance of telomere
      length. Confocal microscopy shows that the release of telomerase to the
      nucleoplasm from sequestration at nucleolar sites is enhanced at the expected
      time of telomere replication. By contrast, in tumour and transformed cells, there
      is an almost complete dissociation of telomerase from nucleoli at all stages of
      the cell cycle. Transfection of the simian virus 40 genome into a primary cell
      line is sufficient to mobilize telomerase from nucleoli to the nucleoplasm.
      Conversely, ionizing radiation induces the reassociation of telomerase with
      nucleoli in both primary and transformed cells. These findings show that
      transformation and DNA damage have opposite effects on the cellular regulation of
      active telomerase, affecting the enzyme's access to both telomeric and
      nontelomeric substrates.

PMID- 12198500
TI  - Invasive cell migration is initiated by guided growth of long cellular
      extensions.
AB  - The migration of border cells during Drosophila melanogaster oogenesis is a
      simple and powerful system for studying invasive cell migration in vivo. Border
      cells are somatic cells that delaminate from the follicular epithelium of an egg
      chamber and invade the germ line cluster. They migrate between the nurse cells to
      reach the oocyte, using DE-cadherin for adhesion to the substratum. Border cells
      take approximately 6 h to migrate a distance of 100 microm. The migration is
      guided by EGFR (epidermal growth factor receptor) and PVR (platelet-derived
      growth factor (PDGF)/vascular endothelial growth factor (VEGF) receptor). Here,
      we show that a single long cellular extension (LCE), several cell diameters in
      length, is formed at the initiation of migration. The LCE may function as a
      'pathfinder' in response to guidance cues. LCE growth requires directional
      guidance signals and specific adhesion to the substratum. Interference with actin
      myosin interactions allows continued LCE growth while preventing translocation of
      the cell bodies. We discuss similarities between LCEs and axons and the use of
      LCE-like structures as a general mechanism for initiating invasive migration in
      vivo.

PMID- 12198503
TI  - Clones: oddities or businesses?

PMID- 12198504
TI  - Web extends to bottom of the world.

PMID- 12198507
TI  - US prepares ground for security clampdown.

PMID- 12198505
TI  - Central Europe braced for tide of pollution in flood aftermath.

PMID- 12198508
TI  - Pike pests ravage Alaska's salmon.

PMID- 12198509
TI  - Fraud inquiry leaves online paper in the ether.

PMID- 12198510
TI  - French agency plans biomedical reformation.

PMID- 12198511
TI  - Hologram technique to flush out features of bog body.

PMID- 12198513
TI  - Almost human...

PMID- 12198514
TI  - Fire from ice.

PMID- 12198515
TI  - Vaccines should be kept even if polio is wiped out.

PMID- 12198516
TI  - Arp2/3 plays no role in muscle contraction.

PMID- 12198517
TI  - Thriving UCSF needs all the space it can get.

PMID- 12198519
TI  - Seeing stars.

PMID- 12198518
TI  - Efforts to revive Serbian science.

PMID- 12198525
TI  - A lethal side-effect.

PMID- 12198527
TI  - Birth of a Solar System.

PMID- 12198528
TI  - Unveiling an ocean phantom.

PMID- 12198526
TI  - Inside the professionals.

PMID- 12198531
TI  - Crossing the highway.

PMID- 12198529
TI  - Apoptosis: sculpture of a fly's head.

PMID- 12198532
TI  - Harnessing hydrogen.

PMID- 12198533
TI  - The molecules of forgetfulness.

PMID- 12198534
TI  - Widespread local house-sparrow extinctions.
AB  - House-sparrow populations have declined sharply in Western Europe in recent
      decades, but the reasons for this decline have yet to be identified, despite
      intense public interest in the matter. Here we use a combination of field
      experimentation, genetic analysis and demographic data to show that a reduction
      in winter food supply caused by agricultural intensification is probably the
      principal explanation for the widespread local extinctions of rural house-sparrow
      populations in southern England. We show that farmland populations exhibit fine
      level genetic structuring and that some populations are unable to sustain
      themselves (sinks), whereas others act as sources.

PMID- 12198535
TI  - Cognitive change and the APOE epsilon 4 allele.
AB  - There is a marked variation in whether people retain sufficient cognitive
      function to maintain their quality of life and independence in old age, even
      among those without dementia, so it would be valuable to identify the
      determinants of normal age-related cognitive change. We have retested non
      demented 80-year-olds who were participants in the Scottish Mental Survey of
      1932, and find that the variation in their non-pathological cognitive change from
      age 11 to 80 is related to their apolipoprotein E (APOE) genotype. This effect of
      the APOE epsilon 4 allele on normal cognitive ageing may be mediated by a
      mechanism that is at least partly independent of its predisposing effect towards
      Alzheimer's disease.

PMID- 12198536
TI  - Fast heating scalable to laser fusion ignition.
AB  - Rapid heating of a compressed fusion fuel by a short-duration laser pulse is a
      promising route to generating energy by nuclear fusion, and has been demonstrated
      on an experimental scale using a novel fast-ignitor geometry. Here we describe a
      refinement of this system in which a much more powerful, pulsed petawatt (10(15)
      watts) laser creates a fast-heated core plasma that is scalable to full-scale
      ignition, significantly increasing the number of fusion events while still
      maintaining high heating efficiency at these substantially higher laser energies.
      Our findings bring us a step closer to realizing the production of relatively
      inexpensive, full-scale fast-ignition laser facilities.

PMID- 12198537
TI  - Tumorigenesis: RAF/RAS oncogenes and mismatch-repair status.
AB  - Genes of the RAF family encode kinases that are regulated by Ras and mediate
      cellular responses to growth signals. Activating mutations in one RAF gene, BRAF,
      have been found in a high proportion of melanomas and in a small fraction of
      other cancers. Here we show that BRAF mutations in colorectal cancers occur only
      in tumours that do not carry mutations in a RAS gene known as KRAS, and that BRAF
      mutation is linked to the proficiency of these tumours in repairing mismatched
      bases in DNA. Our results not only provide genetic support for the idea that
      mutations in BRAF and KRAS exert equivalent effects in tumorigenesis, but also
      emphasize the role of repair processes in establishing the mutation spectra that
      underpin human cancer.

PMID- 12198538
TI  - Coordination of circadian timing in mammals.
AB  - Time in the biological sense is measured by cycles that range from milliseconds
      to years. Circadian rhythms, which measure time on a scale of 24 h, are generated
      by one of the most ubiquitous and well-studied timing systems. At the core of
      this timing mechanism is an intricate molecular mechanism that ticks away in many
      different tissues throughout the body. However, these independent rhythms are
      tamed by a master clock in the brain, which coordinates tissue-specific rhythms
      according to light input it receives from the outside world.

PMID- 12198539
TI  - Open channel structure of MscL and the gating mechanism of mechanosensitive
      channels.
AB  - Mechanosensitive channels act as membrane-embedded mechano-electrical switches,
      opening a large water-filled pore in response to lipid bilayer deformations. This
      process is critical to the response of living organisms to direct physical
      stimulation, such as in touch, hearing and osmoregulation. Here, we have
      determined the structural rearrangements that underlie these events in the large
      prokaryotic mechanosensitive channel (MscL) using electron paramagnetic resonance
      spectroscopy and site-directed spin labelling. MscL was trapped in both the open
      and in an intermediate closed state by modulating bilayer morphology. Transition
      to the intermediate state is characterized by small movements in the first
      transmembrane helix (TM1). Subsequent transitions to the open state are
      accompanied by massive rearrangements in both TM1 and TM2, as shown by large
      increases in probe dynamics, solvent accessibility and the elimination of all
      intersubunit spin-spin interactions. The open state is highly dynamic, supporting
      a water-filled pore of at least 25 A, lined mostly by TM1. These structures
      suggest a plausible molecular mechanism of gating in mechanosensitive channels.

PMID- 12198540
TI  - A short timescale for terrestrial planet formation from Hf-W chronometry of
      meteorites.
AB  - Determining the chronology for the assembly of planetary bodies in the early
      Solar System is essential for a complete understanding of star- and planet
      formation processes. Various radionuclide chronometers (applied to meteorites)
      have been used to determine that basaltic lava flows on the surface of the
      asteroid Vesta formed within 3 million years (3 Myr) of the origin of the Solar
      System. Such rapid formation is broadly consistent with astronomical observations
      of young stellar objects, which suggest that formation of planetary systems
      occurs within a few million years after star formation. Some hafnium-tungsten
      isotope data, however, require that Vesta formed later (approximately 16 Myr
      after the formation of the Solar System) and that the formation of the
      terrestrial planets took a much longer time (62(-14)(+4504) Myr). Here we report
      measurements of tungsten isotope compositions and hafnium-tungsten ratios of
      several meteorites. Our measurements indicate that, contrary to previous results,
      the bulk of metal-silicate separation in the Solar System was completed within
      <30 Myr. These results are completely consistent with other evidence for rapid
      planetary formation, and are also in agreement with dynamic accretion models that
      predict a relatively short time (approximately 10 Myr) for the main growth stage
      of terrestrial planet formation.

PMID- 12198541
TI  - Rapid accretion and early core formation on asteroids and the terrestrial planets
      from Hf-W chronometry.
AB  - The timescales and mechanisms for the formation and chemical differentiation of
      the planets can be quantified using the radioactive decay of short-lived
      isotopes. Of these, the (182)Hf-to-(182)W decay is ideally suited for dating core
      formation in planetary bodies. In an earlier study, the W isotope composition of
      the Earth's mantle was used to infer that core formation was late (> or = 60
      million years after the beginning of the Solar System) and that accretion was a
      protracted process. The correct interpretation of Hf-W data depends, however, on
      accurate knowledge of the initial abundance of (182)Hf in the Solar System and
      the W isotope composition of chondritic meteorites. Here we report Hf-W data for
      carbonaceous and H chondrite meteorites that lead to timescales of accretion and
      core formation significantly different from those calculated previously. The
      revised ages for Vesta, Mars and Earth indicate rapid accretion, and show that
      the timescale for core formation decreases with decreasing size of the planet. We
      conclude that core formation in the terrestrial planets and the formation of the
      Moon must have occurred during the first approximately 30 million years of the
      life of the Solar System.

PMID- 12198543
TI  - Near-infrared sensitivity enhancement of photorefractive polymer composites by
      pre-illumination.
AB  - Among the various applications for reversible holographic storage media, a
      particularly interesting one is time-gated holographic imaging (TGHI). This
      technique could provide a noninvasive medical diagnosis tool, related to optical
      coherence tomography. In this technique, biological samples are illuminated
      within their transparency window with near-infrared light, and information about
      subsurface features is obtained by a detection method that distinguishes between
      reflected photons originating from a certain depth and those scattered from
      various depths. Such an application requires reversible holographic storage media
      with very high sensitivity in the near-infrared. Photorefractive materials, in
      particular certain amorphous organic systems, are in principle promising
      candidate media, but their sensitivity has so far been too low, mainly owing to
      their long response times in the near-infrared. Here we introduce an organic
      photorefractive material -- a composite based on the poly(arylene vinylene)
      copolymer TPD-PPV -- that exhibits favourable near-infrared characteristics. We
      show that pre-illumination of this material at a shorter wavelength before
      holographic recording improves the response time by a factor of 40. This process
      was found to be reversible. We demonstrate multiple holographic recording with
      this technique at video rate under practical conditions.

PMID- 12198542
TI  - Metal-insulator transition in chains with correlated disorder.
AB  - According to Bloch's theorem, electronic wavefunctions in perfectly ordered
      crystals are extended, which implies that the probability of finding an electron
      is the same over the entire crystal. Such extended states can lead to metallic
      behaviour. But when disorder is introduced in the crystal, electron states can
      become localized, and the system can undergo a metal-insulator transition (also
      known as an Anderson transition). Here we theoretically investigate the effect on
      the physical properties of the electron wavefunctions of introducing long-range
      correlations in the disorder in one-dimensional binary solids, and find a
      correlation-induced metal-insulator transition. We perform numerical simulations
      using a one-dimensional tight-binding model, and find a threshold value for the
      exponent characterizing the long-range correlations of the system. Above this
      threshold, and in the thermodynamic limit, the system behaves as a conductor
      within a broad energy band; below threshold, the system behaves as an insulator.
      We discuss the possible relevance of this result for electronic transport in DNA,
      which displays long-range correlations and has recently been reported to be a one
      dimensional disordered conductor.

PMID- 12198544
TI  - Hydrogen from catalytic reforming of biomass-derived hydrocarbons in liquid
      water.
AB  - Concerns about the depletion of fossil fuel reserves and the pollution caused by
      continuously increasing energy demands make hydrogen an attractive alternative
      energy source. Hydrogen is currently derived from nonrenewable natural gas and
      petroleum, but could in principle be generated from renewable resources such as
      biomass or water. However, efficient hydrogen production from water remains
      difficult and technologies for generating hydrogen from biomass, such as
      enzymatic decomposition of sugars, steam-reforming of bio-oils and gasification,
      suffer from low hydrogen production rates and/or complex processing requirements.
      Here we demonstrate that hydrogen can be produced from sugars and alcohols at
      temperatures near 500 K in a single-reactor aqueous-phase reforming process using
      a platinum-based catalyst. We are able to convert glucose -- which makes up the
      major energy reserves in plants and animals -- to hydrogen and gaseous alkanes,
      with hydrogen constituting 50% of the products. We find that the selectivity for
      hydrogen production increases when we use molecules that are more reduced than
      sugars, with ethylene glycol and methanol being almost completely converted into
      hydrogen and carbon dioxide. These findings suggest that catalytic aqueous-phase
      reforming might prove useful for the generation of hydrogen-rich fuel gas from
      carbohydrates extracted from renewable biomass and biomass waste streams.

PMID- 12198545
TI  - Pfiesteria shumwayae kills fish by micropredation not exotoxin secretion.
AB  - Pfiesteria piscicida and P. shumwayae reportedly secrete potent exotoxins thought
      to cause fish lesion events, acute fish kills and human disease in mid-Atlantic
      USA estuaries. However, Pfiesteria toxins have never been isolated or
      characterized. We investigated mechanisms by which P. shumwayae kills fish using
      three different approaches. Here we show that larval fish bioassays conducted in
      tissue culture plates fitted with polycarbonate membrane inserts exhibited
      mortality (100%) only in treatments where fish and dinospores were in physical
      contact. No mortalities occurred in treatments where the membrane prevented
      contact between dinospores and fish. Using differential centrifugation and
      filtration of water from a fish-killing culture, we produced 'dinoflagellate',
      'bacteria' and 'cell-free' fractions. Larval fish bioassays of these fractions
      resulted in mortalities (60-100% in less than 24 h) only in fractions containing
      live dinospores ('whole water', 'dinoflagellate'), with no mortalities in 'cell
      free' or 'bacteria'-enriched fractions. Videomicrography and electron microscopy
      show dinospores swarming toward and attaching to skin, actively feeding, and
      rapidly denuding fish of epidermis. We show here that our cultures of actively
      fish-killing P. shumwayae do not secrete potent exotoxins; rather, fish mortality
      results from micropredatory feeding.

PMID- 12198546
TI  - Protein phosphatase 1 is a molecular constraint on learning and memory.
AB  - Repetition in learning is a prerequisite for the formation of accurate and long
      lasting memory. Practice is most effective when widely distributed over time,
      rather than when closely spaced or massed. But even after efficient learning,
      most memories dissipate with time unless frequently used. The molecular
      mechanisms of these time-dependent constraints on learning and memory are
      unknown. Here we show that protein phosphatase 1 (PP1) determines the efficacy of
      learning and memory by limiting acquisition and favouring memory decline. When
      PP1 is genetically inhibited during learning, short intervals between training
      episodes are sufficient for optimal performance. The enhanced learning correlates
      with increased phosphorylation of cyclic AMP-dependent response element binding
      (CREB) protein, of Ca(2+)/calmodulin-dependent protein kinase II (CaMKII) and of
      the GluR1 subunit of the AMPA receptor; it also correlates with CREB-dependent
      gene expression that, in control mice, occurs only with widely distributed
      training. Inhibition of PP1 prolongs memory when induced after learning,
      suggesting that PP1 also promotes forgetting. This property may account for
      ageing-related cognitive decay, as old mutant animals had preserved memory. Our
      findings emphasize the physiological importance of PP1 as a suppressor of
      learning and memory, and as a potential mediator of cognitive decline during
      ageing.

PMID- 12198547
TI  - Shh and Gli3 are dispensable for limb skeleton formation but regulate digit
      number and identity.
AB  - Most current models propose Sonic hedgehog (Shh) as the primary determinant of
      anteroposterior development of amniote limbs. Shh protein is said to be required
      to direct the formation of skeletal elements and to specify digit identity
      through dose-dependent activation of target gene expression. However, the
      identity of genes targeted by Shh, and the regulatory mechanisms controlling
      their expression, remain poorly understood. Gli3 (the gene implicated in human
      Greig cephalopolysyndactyly syndrome) is proposed to negatively regulate Shh by
      restricting its expression and influence to the posterior mesoderm. Here we
      report genetic analyses in mice showing that Shh and Gli3 are dispensable for
      formation of limb skeletal elements: Shh(-/-) Gli3(-/-) limbs are distally
      complete and polydactylous, but completely lack wild-type digit identities. We
      show that the effects of Shh signalling on skeletal patterning and ridge
      maintenance are necessarily mediated through Gli3. We propose that the function
      of Shh and Gli3 in limb skeletal patterning is limited to refining autopodial
      morphology, imposing pentadactyl constraint on the limb's polydactyl potential,
      and organizing digit identity specification, by regulating the relative balance
      of Gli3 transcriptional activator and repressor activities.

PMID- 12198548
TI  - T-cell engagement of dendritic cells rapidly rearranges MHC class II transport.
AB  - Assembly of major histocompatibility complex (MHC) molecules, which present
      antigen in the form of short peptides to T lymphocytes, occurs in the endoplasmic
      reticulum; once assembled, these molecules travel from the endoplasmic reticulum
      to their final destination. MHC class II molecules follow a route that takes them
      by means of the endocytic pathway, where they acquire peptide, to the cell
      surface. The transport of MHC class II molecules in 'professional' antigen
      presenting cells (APCs) is subject to tight control and responds to inflammatory
      stimuli such as lipopolysaccharide. To study class II transport in live APCs, we
      replaced the mouse MHC class II gene with a version that codes for a class II
      molecule tagged with enhanced green fluorescent protein (EGFP). The resulting
      mice are immunologically indistinguishable from wild type. In bone-marrow-derived
      dendritic cells, we observed class II molecules in late endocytic structures with
      transport patterns similar to those in Langerhans cells observed in situ. We show
      that tubular endosomes extend intracellularly and polarize towards the
      interacting T cell, but only when antigen-laden dendritic cells encounter T cells
      of the appropriate specificity. We propose that such tubulation serves to
      facilitate the ensuing T-cell response.

PMID- 12198549
TI  - Dendritic cell maturation triggers retrograde MHC class II transport from
      lysosomes to the plasma membrane.
AB  - Central to the initiation of immune responses is recognition of peptide antigen
      by T lymphocytes. The cell biology of dendritic cells makes them ideally suited
      for the essential process of antigen presentation. Their life cycle includes
      several stages characterized by distinct functions and mechanisms of regulation.
      Immature dendritic cells synthesize large amounts of major histocompatibility
      complex class II molecules (MHC II), but the alpha beta-dimers are targeted to
      late endosomes and lysosomes (often referred to as MHC class II compartments)
      where they reside unproductively with internalized antigens. After exposure to
      microbial products or inflammatory mediators, endocytosis is downregulated, the
      expression of co-stimulatory molecules is enhanced, and newly formed immunogenic
      MHC II-peptide complexes are transported to the cell surface. That these MHC II
      molecules reach the surface is surprising, as the lysosomes comprise the terminal
      degradative compartment of the endocytic pathway from which exogenous components
      generally cannot be recovered intact. Here we have visualized this pathway in
      live dendritic cells by video microscopy, using cells expressing MHC II tagged
      with green fluorescent protein (GFP). We show that on stimulation, dendritic
      cells generate tubules from lysosomal compartments that go on to fuse directly
      with the plasma membrane.

PMID- 12198551
TI  - Reverse engineering of the giant muscle protein titin.
AB  - Through the study of single molecules it has become possible to explain the
      function of many of the complex molecular assemblies found in cells. The protein
      titin provides muscle with its passive elasticity. Each titin molecule extends
      over half a sarcomere, and its extensibility has been studied both in situ and at
      the level of single molecules. These studies suggested that titin is not a simple
      entropic spring but has a complex structure-dependent elasticity. Here we use
      protein engineering and single-molecule atomic force microscopy to examine the
      mechanical components that form the elastic region of human cardiac titin. We
      show that when these mechanical elements are combined, they explain the
      macroscopic behaviour of titin in intact muscle. Our studies show the functional
      reconstitution of a protein from the sum of its parts.

PMID- 12198550
TI  - A chromatin remodelling complex that loads cohesin onto human chromosomes.
AB  - Nucleosomal DNA is arranged in a higher-order structure that presents a barrier
      to most cellular processes involving protein DNA interactions. The cellular
      machinery involved in sister chromatid cohesion, the cohesin complex, also
      requires access to the nucleosomal DNA to perform its function in chromosome
      segregation. The machineries that provide this accessibility are termed chromatin
      remodelling factors. Here, we report the isolation of a human ISWI (SNF2h)
      containing chromatin remodelling complex that encompasses components of the
      cohesin and NuRD complexes. We show that the hRAD21 subunit of the cohesin
      complex directly interacts with the ATPase subunit SNF2h. Mapping of hRAD21,
      SNF2h and Mi2 binding sites by chromatin immunoprecipitation experiments reveals
      the specific association of these three proteins with human DNA elements
      containing Alu sequences. We find a correlation between modification of histone
      tails and association of the SNF2h/cohesin complex with chromatin. Moreover, we
      show that the association of the cohesin complex with chromatin can be regulated
      by the state of DNA methylation. Finally, we present evidence pointing to a role
      for the ATPase activity of SNF2h in the loading of hRAD21 on chromatin.

PMID- 12198552
TI  - Methods for structural and functional analysis of an RNA hexamer of bacterial
      virus phi29 DNA packaging motor.
AB  - During multiplication and maturation, the lengthy genomic DNA of dsDNA viruses is
      translocated with remarkable velocity into a limited space within the procapsid
      and packaged to crystalline density. A viral DNA-packaging motor accomplishes
      this energy consuming motion task. An RNA molecule of bacterial virus phi29 has
      been found to be a vital component of the DNA-packaging motor. Six pRNAs form a
      hexagonal complex to gear the DNA translocating machine using a mechanism similar
      to the driving of a bolt with a hex nut. Sequential action of six RNA molecules
      to drive the motor is similar to the consecutive firing of six cylinders of a car
      engine. This article reviews the structure of pRNA to demonstrate that its
      structure plays a vital role in its function, and focuses on methods and unique
      approaches that lead to the elucidation of pRNA structure.

PMID- 12198553
TI  - [Application of bio-mass spectrometry in cellular signal transduction].
AB  - The quickly developing techniques of biological mass spectrometry (bio-MS) in
      recent years realized the high throughput identification of proteins by
      determining the accurate mass values of trypsin digested peptides and the
      randomly selected peptide sequence tags, and have been successfully used in the
      studies of protein interactions and post-translational modification such as the
      phosphorylation. Compared to the conventional approaches, the above techniques
      can identify all the phosphorylated proteins (including their phosphorylated
      amino acid sites) involved in a multi-signal pathway in a single experiment, and
      they have been developed into a hot-spot of proteomics. The three strategies for
      the application of bio-MS in the above fields are briefly reviewed.

PMID- 12198554
TI  - In vivo CTL immunity can be elicited by OVA-linker-beta2m fusion protein.
AB  - To study the effect of OVA-linker-beta2m fusion protein as an immunogen to induce
      CTL mediated immune response in mice. The beta2m gene was amplified by PCR.
      OVA(257-264) peptide sequence and an 8-amino acid linker were added to the COOH
      terminus of beta2m gene, and then cloned into pE42b(+) vector. After that, gene
      expression, protein purification and refolding were conducted. Then the protein
      product was used as an immunogen to induce an efficient CTL mediated immune
      response in vivo. Specific CTL responses were demonstrated by H-2K(b)-OVA
      tetramer staining and cytotoxicity assay. Extracelluar IFN-gamma was also
      quantitatively analyzed. The results showed that specific CTL response could be
      induced in vivo by OVA-linker-beta2m fusion protein. Generation of terameric
      peptide-MHC complexes in vitro is a powerful tool to stain specific CTL.

PMID- 12198555
TI  - [Cloning of Candida albicans CaBEM1 and its role in filamentous growth of
      Saccharomyces cerevisiae].
AB  - The pathogenic fungus Candida albicans has a dimorphic transition in various
      environmental conditions. Many regulatory factors and several transduction
      pathways have been identified in controlling filamentous growth. G(1) cyclins
      Cln1 and Cln2 have been reported as involved in the control of morphogenesis in
      Saccharomyces cerevisiae. Diploid cln1/cln1 and cln2/cln2 strains completely lost
      the ability to form pseudohyphae. A C. albicans genomic DNA library was
      introduced into cln1/cln1   and cln2/cln2 mutants to screen genes which could
      complement its filamentous growth defect. In this screening a BEM1 homolog,
      CaBEM1, was identified. The CaBEM1 gene has an ORF of 1 899 bp, encoding a
      putative protein of 632 amino acids. The CaBem1 protein shares highest homology
      in amino acids with Bem1 (38%) of S. cerevisiae and Scd2 (32%) of
      Schizosaccharomyces pombe. Sequence analysis showed that the CaBem1 contains two
      N-terminal SH3 domains, a PX domain and a C-terminal PB1 domain. It is believed
      these domains are required for binding to proteins involved in polarized growth
      in S. cerevisiae and S. pombe. Ectopic expression of the CaBEM1 gene in diploid
      S. cerevisiae suppressed defects in filamentous growth of some mutants under
      nitrogen starvation conditions. This suppression bypassed MAPK pathway and
      cAMP/PKA pathway in filamentous growth. These results suggest that the CaBem1
      protein may be a downstream component of these two signal transduction pathways
      of filament formation.

PMID- 12198556
TI  - [Identification of functional region of helicase gene promoter in Bombyx mori
      nuclear polyhedrosis virus].
AB  - DNA helicases are essential for replication of baculoviruses. It was found that
      the helicase gene promoter of Bombyx mori nuclear polyhedrosis virus, including
      510 bp upstream of ATG, had both early and late RNA initiation sites and could be
      recognized by cellular RNA polymerase. Transient expression assays in uninfected
      Sf-21 cells indicated that the helicase gene promoter could be classified as a
      delayed-early gene promoter. Deletion analysis by PCR showed that the regulation
      region of its basic transcription was mainly within -510 to -410 bp upstream of
      ATG. However, the basic activity was still detected with a deletion to -98 bp
      relative to ATG. In the presence of viral factors, deletion between -510 to -410
      bp relative to ATG did not significantly reduce the promoter activity compared to
      the full-length promoter (510 bp). The remarkable reduction in the promoter
      activity was observed with continuous deletions. It suggests, therefore, that cis
      acting elements responsive to viral factors are mainly located within the range
      of -410 to -309 bp upstream of ATG.

PMID- 12198557
TI  - [Self-aggregation of the structural protein encoded by rice ragged stunt
      Oryzavirus genome segment 8].
AB  - Rice ragged stunt oryzavirus (RRSV) is a member of the genus oryzavirus within
      the family Reoviridae. Its genome consists of ten segments of dsRNA. The
      functions of all products encoded by these viral genome segments, except one
      encoded by S9, have not yet been elucidated. In the present study, the ORF of S 8
      of RRSV-Philippines isolate was sequenced and expressed in E. coli. The 67 kD
      product of S8 could be self-cleaved into two fragments with molecular weights of
      43 kD and 26 kD. Western blotting indicated that both 67 kD and 43 kD products
      were major structural proteins of the virus. It was also found that the 67 kD
      protein could self  aggregate into aggregates with higher sedimentation rate in
      sucrose gradients during centrifugation. Moreover, the self-aggregation process
      could be accelerated by the complex of S6 product and genome dsRNAs of RRSV.
      These results suggest that the S8 products, 67 kD or 43 kD, may be the structural
      components of the viral inner-capsid.

PMID- 12198558
TI  - [Restin expressed in vivo suppresses the growth of tumors in nude mice].
AB  - Restin, a homologous protein of endostatin (62% homology), is the NC domain of
      collagen XV at C-terminal. The recombinant restin expressed in E. coli had the
      ability to suppress the proliferation of bovin aortic endothelial cells and cause
      apoptosis. In this report, mouse restin gene was fused with a sequence of  human
      plasminogen signal peptide by PCR and cloned into eukaryotic expression vector
      pCDNA3. The plasmid containing restin gene was named pCDNAXV and was transfected
      into human hepatoma cell line Bel7404. Stable transfected clones were screened
      and expression of restin was confirmed by RT-PCR and Western blot. The
      proliferated cells were injected subcutaneusly into nude mice. The growth of
      tumors formed by cells transfected with restin gene was much slower than that of
      control group. These results indicated that the expressed restin in vivo could
      suppress the growth of tumor, and this suppression might be achieved by
      restraining angiogenesis since the restin had no effect on the proliferation of
      tumor cells. At the same time, this report provided a new method to investigate
      the effect of anti-angiogenetic proteins on the tumor growth.

PMID- 12198560
TI  - [Redox properties and conformational changes of DsbA protein from Escherichia
      coli periplasm].
AB  - DsbA protein, a disulfide bond enzyme in Escherichia coli periplasm, catalyzes
      mainly disulfide bond formation of proteins. Site-directed mutagenes is combined
      with Trp-analog labeling technique was used to investigate the redox properties
      and conformational changes of DsbA. The results show that: (1) DsbA, as an
      oxidase, can catalyze disulfide bond formation efficiently. The reduced form is
      more stable than the oxidized form, suggesting that the strong oxidizing force of
      DsbA comes from the tense conformation of the oxidized form. (2) The alteration
      of local environment around Trp(76) between redox forms is responsible for the
      special fluorescence phenomenon of DsbA. (3) The result from (19)F-NMR study
      provides further evidence that the local conformation of Trp(76) is dramatically
      affected during the transformation of redox forms, but that of Trp(126) remains
      unaffected.

PMID- 12198559
TI  - [Isolation and identification of proteins with anti-tumor and fibrinolysogen
      kinase activities from Eisenia foetida].
AB  - Proteins from Eisenia foetida possess many biological activities. A group of
      proteins precipitated by ethanol were isolated and purified by Sephadex G-75 and
      HiPrep 16/60 DEAE columns, then identified by one- or two- dimensional
      electrophoresis and mass spectrometry. 2D gel experiments displayed that the pI
      of proteins from Eisenia foetida  were mainly from 3.0 to 4.0. Anti-tumor and
      kinase activities were determined by in vitro experiments. The enthanol fraction
      D2(8) showed both of the activities. These ethanol-precipitated proteins were
      identified further by native polyacrylamide electrophoresis, the protein spots
      were cut off from gels and digested by trypsin, the peptide mass fingerprints
      (PMFs) were determined by mass spectrometry. PMF, molecular weight, amino acid
      composition and N-terminus of 6 proteins were characterized, and band 9 was
      identified as D2(8). The results suggested that there exist proteins in Eisenia
      foetida possessed both anti-tumor and fibrinolysogen kinase activities. These
      methods can be used for identification of the natural bioactive proteins.

PMID- 12198561
TI  - [Purification and partial biochemical characterization of phenoloxidase from
      Penaeus chinensis].
AB  - Using L-DOPA as a probe, phenoloxidase (PO) from Penaeus chinensis hemolymph was
      purified by gel-filtration and ion-exchange chromatography, and characterized in
      terms of its molecular weight and enzymatic properties in this study. It was
      found that prophenoloxidase (proPO) isolated as monomeric protein had a molecular
      weight of 87.5 kD, and a 77 kD phenoloxidase molecule was often contained in
      preparations. The 87.5 kD proPO had a very low enzymatic activity on 0.02 mmol/L
      L-DOPA, whereas the 77 kD PO had a very high enzymatic activity on L-DOPA.
      Enzymatic activity of PO against L-DOPA was optimal at pH 6.0, temperature of 40
      degrees, and with an apparent K(m) value of 1.99 mmol/L. The PO activity was
      extremely sensitive to ascorbic acid, cysteine and dithiothreitol, very sensitive
      to thio urea, however not sensitive to sodium sulfite, citric acid and benzoic
      acid, confirmed that it was a phenoloxidase, combined with its specific oxidase
      activity on substrate of monophenol and L-DOPA, indicate that it was a tyrosinase
      type phenoloxidase. This enzyme is very sensitive to EDTA and metal ions, its
      activity is strongly enhanced by Mg(2+) and strongly inhibited by Cu(2+), which
      indicates that this PO is probably a kind of metalloenzyme.

PMID- 12198562
TI  - [Expression, purification and characterization of human prorelaxin-like-protein
      H2 in Escherichia coli].
AB  - The cDNA gene encoding human prorelaxin H2 was subcloned from plasmid pMAL p2X
      hRLX H2 into the EcoRI and BamHI sites of prokaryotic expression vector pBV220,
      resulting in the recombinant plasmid pBV220-hPRLX H2, which was subsequently
      transformed into Escherichia coli DH5arg;. The target gene was highly expressed
      in the form of inclusion body by thermoinduction at 42 degrees. Recombinant human
      Met-prorelaxin-like-protein H2 was refolded in vitro, purified by Sephadex G-75
      gel filtration chromatography and reverse phase fast protein liquid
      chromatography. The yield was approximately 2-3 mg/L. The purified recombinant
      human Met-prorelaxin-like-protein H2 was shown to be a single band by 15% SDS
      PAGE and gave correct amino acid composition of Met-prorelaxin. Molecular weight
      of the purified recombinant human Met-prorelaxin-like-protein H2 was measured to
      be 18 390.4 (calculated theoretical value 18 392.3) by matrix assisted laser
      desorption ionization time-of-flight mass spectroscopy.

PMID- 12198563
TI  - [Screening and identification of tumor related genes in early stages of
      transformed NIH3T3 cells associated with overexpressed PTPalpha].
AB  - An inducible-PTPalpha expression system was used to screen differential
      expression genes in NIH3T3 cells overexpressing PTPalpha, which could be used as
      a model for studying mechanism of tumorigenesis at early stage. After PTPalpha
      induction for 24 h, 65 differential bands were obtained, among which, there were
      29 known genes, 12 known EST, 6 novel EST by bioinformatic analysis. Functions of
      the known genes were related to signal transduction, structural/adhesion, energy
      metabolism, transcription/translation, ribosome and apoptosis. The differential
      expression of the genes coding for G protein, TCR, Trx-related protein, caveolin
      1 was verified by RT-PCR and Northern blot. The results showed that the
      expression of numerous genes was changed after the induction of PTPalpha for 24
      h, these genes are related to many cellular physiological functions, and some of
      them play important roles in the early stage of tumorigenesis. The results
      provide basis for further exploring the molecular mechanism of tumorigenesis and
      these genes may well be candidate targets for gene therapy.

PMID- 12198564
TI  - [Generation and analysis of a repeat DNA fragment of SeMNPV by serial undiluted
      passage in Se301 insect cells].
AB  - Two major clades, designated Groups I and II, of nucleopolyhedroviruses (NPVs)
      from insect hosts have been previously identified. In order to gain insight into
      DNA replication of Spodoptera exigua multicapsid nucleopolyhedrovirus (SeMNPV,
      Groups II), the essential cis-acting DNA segments were studied. A strain, named
      Se-4, was plaque-purified from SeMNPV isolate US1. PCR, ELT-PCR and REN showed
      that Se-4 was genetically relatively homogeneous and retained the full-length of
      a hypervariable region which is usually prone to deletion from SeMNPV genome. To
      study the stability of this isolate in vitro, Se-4 was serially passaged in the
      Se301 cell line up to 10 times without dilution. Intracellular viral DNA
      extracted from every passage was analyzed by REN. A novel 3.5 kb PstI fragment
      was observed in passage 7 and the relative intensities of the bands increased
      with subsequent passages. In passage 10, the molar ratio of the fragment was much
      higher than those of any other viral DNA fragments. This fragment was thus
      expected to contain an important cis-acting element for SeMNPV DNA replication.
      The fragment was cloned and sequenced and it was found that it overlapped 3 525
      bp with the published SeMNPV genome sequence (GenBank AF169823), from 81 014 nt
      to 84 538 nt. The region contained the SeMNPV non-hr origin (ori) of DNA
      replication and some ORFs including partial vlf-1, partial p26, Se84 as well
      asSe83, Se85, Se86, which are unique to SeMNPV. As compared to Autographa
      californica MNPV (Groups I), which also generated hypermolar DNA fragments
      containing the non-hr ori by serial undiluted passage in IPLB-SF-21 cell culture,
      our results provided in vitro evidence that the non-hr ori may also play an
      important role in the viral infection cycle of Groups II NPVs.

PMID- 12198565
TI  - [Determination of the D- and L-configurations of amino deoxy sugars by (S)-TBMB
      carboxylic acid, a fluorescent chiral derivatization reagent].
AB  - D- and L- amino sugars were coupled with (S)-TBMB   (S)-TBMB = (S)-2-tert-butyl-2
      methyl-1, 3-benzodioxole  carbonyl chloride, a fluorescent chiral reagent,
      followed by per-O-acetylation. The reactions yielded diastereomeric per-O
      acetylated   N-(S)-TBMB carbonyl amino sugars. Their (1)HNMR signals, especially
      the strong singlet peaks of tert-Bu and Me groups were diagnostic for the
      determination of the D-, L- configurations of amino sugar. Furthermore, a simple
      and highly sensitive method for the determination of the D-, L- configuration of
      amino deoxy sugars was developed based on the same fluorescent labeling method
      and reverse phase HPLC. The total time in analysis is less than two hours and the
      detection limit of the method is 0.2 picomolar.

PMID- 12198566
TI  - [The mechanism of interferon-gamma increases growth hormone expression in rat
      pituitary GH(3) cells].
AB  - The method of luciferase reporter gene was used to investigate the effect of
      interferon-gamma (IFN-gamma) on the activity of human growth hormone (hGH) gene
      promoter in rat pituitary GH(3) cells, to elucidate the post-receptor signal
      transduction pathway and the key promoter sequence which mediated the action of
      IFN-gamma. The luciferase expression plasmid pGL(3)-484-Luc containing hGH gene
      promoter (-484-2 bp) and luciferase reporter gene were transfected alone or
      cotransfected with pituitary specific transcription factor Pit-1 expression
      plasmid (PcDNA-Pit-1-cDNA) or Pit-1 antisense oligonucleotide (Pit-1 OND) into
      rat GH(3) cells. The changes of luciferase expression in the GH(3) cells were
      determined, after treatment with IFN-gamma or IFN-gamma plus inhibitors of
      intracellular signaling pathways, to observe the effect of IFN-gamma and these
      inhibitors on the activity of hGH gene promoter. The various deletion constructs
      of Luc reporter: pGL(3)-380-Luc, pGL(3)-250-Luc, pGL(3)-132-Luc and pGL(3)-66
      Luc, which contained the -380-2 bp, -250-2 bp, -132-2 bp and -66-2 bp sequences
      of hGH gene promoter, respectively, were transfected into GH(3) cells, then the
      changes of luciferase expression in the GH(3) cells were assayed, after treatment
      with IFN-gamma, to find out the key sequence which mediated the action of IFN
      gamma. Our results showed that IFN-gamma (10(5) u/L, 10(6) u/L) could increase
      luciferase expression in GH(3)cells transfected with pGL(3)-484-Luc alone, the
      maximal action being 131% of the control (P<0.001). Among the inhibitors of
      intracellular signaling transduction pathways, only mitogen activated protein
      kinases (MAPK) inhibitor PD98059 (40 micromol/L) could completely blocked the
      stimulatory effect of IFN-gamma on hGH gene promoter activity. Pit-1
      overexpression or inhibited Pit-1 expression, both had no effect on IFN-gamma
      induced hGH gene promoter activity. When various deletion constructs of Luc
      reporter were transfected into GH(3) cells, only pGL(3)380-Luc and pGL(3)250-Luc
      still responded to IFN-gamma. In conclusion, IFN-gamma could increase the
      activity of hGH gene promoter in rat pituitary GH(3) cells. This stimulatory
      effect of IFN-gamma may be associated with the intracellular MAPK signaling
      pathway and with -252--132 bp sequence in hGH gene promoter, but had no
      relationship with pituitary specific transcription factor Pit-1.

PMID- 12198567
TI  - [Enhancement by hypoxia of antisense VEGF(165) gene expression in esophageal
      cancer cells].
AB  - To demonstrate effects of antisense VEGF(165) to suppress esophageal cancer cells
      and to improve efficacy of the gene therapy of tumor by using hypoxic
      environment, hypoxia response element (HRE) was cloned from promoter of VEGF by
      PCR and employed to construct an eukaryotic expression vector containing
      luciferase and antisense VEGF(165) by using recombinant DNA techniques. The
      recombinant vectors were transfered into esophageal cancer cells by lipofectin
      methods, and hypoxia inducible reporter gene expression was determined by
      luminometer and the expression of antisense VEGF was evaluated indirectly by
      ELISA that detected of VEGF. The esophageal cells tansfected by antisense
      VEGF(165) gene were transplanted into nude mice, in order to evaluate the
      suppressive effect of antisense VEGF(165). Our results showed that, in vitro,
      hypoxia increased expression of reporter gene to 3 780 % and enhanced greatly
      expression of antisense VEGF. In vivo, the growth of esophageal cancer cells
      transfected by antisense VEGF in the vector containing HRE was suppressed more
      significantly, with suppression rate being 71.1%, than that by the vector without
      HRE, whose inhibiting rate 56.1%. It was concluded that antisense VEGF(165)
      suppressed significantly growth of esophageal cancer, and by using a gene
      expression vector containing HRE, the expression of target genes could be
      regulated autonomously by hypoxic environment of tumor and the efficiency of gene
      therapy could be greatly improved.

PMID- 12198568
TI  - [Nano-ESI-MS/MS identification on apoptosis qssociated proteins induced by
      inhibiting ubiquitin-proteasome pathway].
AB  - CapLC-ESI-MS/MS and nano-ESI-MS/MS techniques were used to identify the apoptosis
      associated proteins induced by inhibiting the ubiquitin-proteasome pathway in
      Mo7e leukaemic cells. In 2-DE, spot H was found to initiate its overexpression at
      2 h after the inhibition and reached its peak at 6 h. It was identified as Rho
      GDI beta protein after the tandem mass spectrum and after the sequence of its
      tryptic peptides were obtained by the ESI-MS/MS techniques. It was not revealed
      by peptide mass fingerprint using MALDI-TOF-MS. Other two spots induced by the
      inhibition appeared close to spot H were also revealed identical to Rho GDI brg;,
      possibly due to unknown modifications.

PMID- 12198569
TI  - [In vitro selection and affinity function of the aptamers to Bacillus anthracis
      spores by SELEX].
AB  - To obtain oligonucleotide aptamers, specifically binding to Bacillus anthracis
      spores, and to find the relationship between the structures and the affinities,
      and to determine whether the aptamers can be used as a novel molecule for spore
      detection, a synthetic 35 mer random DNA library was subjected to 18 rounds of
      selection by using SELEX (systematic evolution of ligands by exponential
      enrichment) protocol against spores of Bacillus anthracis vaccine strain A. 16R.
      The selected aptamers were cloned and sequenced. Software packages CLUSTALX (1.8)
      and DNASIS v2.5 were employed to analyze the conserved sequences and second
      structures of the aptamers, respectively. Affinities of aptamers to the spores
      were visualized by biotin streptavidin horseradish peroxidase system. DAB was
      used to visualize signals, as an assay method. A membrane-based hybrid sandwich
      assay was developed for detecting Bacillus anthracic spores by using a 5'
      biotinylated ssDNA aptamers and anti-spore antibodies. PCR amplification band
      pattern of the first round selection was different from that of the ninth round.
      The binding assay demonstrated that the affinity of the eighteenth round pool
      increased thirty-seven folds more than that of the first round pool. The
      affinities of the aptamers were different: the highest A at 450 nm was 1.20, and
      the lowest was 0.20. The secondary structure analysis revealed possible stem-loop
      and hairpin structures for binding to the spores. The colorimetry on the immuno
      membrane got the best signal with a ratio of 16 microgram aptamer to 4x10(7)
      spores. A set of aptamers with considerable binding affinity to Bacillus
      anthracis spores was successfully selected from the initial random ssDNA pool.
      The stem-loop and hairpin at 5' end of the aptamers worked as the main motif in
      the interaction between oligonucleotides and spores, while the neighbor bases of
      the triple structure might affect the stability. Therefore ssDNA aptamers seem to
      be a type of potential diagnostic molecule.

PMID- 12198570
TI  - [Long-term outcome of gfp gene modified human RPE xenografts into the subretinal
      space of rabbits].
AB  - The possibility of delivery genes to retina by using retinal pigment epithelium
      (RPE) transplantation was investigated. Cultured human adult RPE cells were
      transfected with retrovirus encoding green fluorescent protein (GFP), then GFP
      expressing RPE cells were transplanted into the subretinal space of rabbits
      through pars plana vitrectomy under microscopy. The transplant sites were
      examined in vivo by ophthalmoscope for fluorescence. The animals were
      euthanatized at 1, 2, 3, 4, 6, 10, 11, 14, 18, 20, 23, 24, 25, 33, 54 weeks,
      respectively, and the retinas were studied histologically, including epi
      fluorescent microscopy, confocal microscopy and transmission electron microscopy.
      The GFP-expressing transplant could be followed in the living retina up to 21
      days by ophthalmoscope. The epi-fluorescent microscopy examination disclosed
      survival of the transplanted cells in 1 year with continual and significant GFP
      expression. It was observed the transplanted hRPE-gfp cells were not only present
      at transplant sites but spread over two to three quarters of retina. Generally,
      RPE xenografts integrated individually into host RPE in a regular cobblestones
      arrangement or formed a monolayer sheet between host RPE and neural retina. It
      was observed that intravitreal injection of FK-506 weekly improved the survival
      of RPE xenografts and reduced the infiltration of mononuclear microphages and
      lymphocytes in choroids from 1 through 14 weeks after transplantation. The
      results demonstrate a long-term survival of gene modified human RPE xenografts
      into the subretinal space of rabbits and support the feasibility of this approach
      for delivery genes to retina.

PMID- 12198571
TI  - Comparison of 5-aminolevulinic acid and its hexylester mediated photodynamic
      action on human hepatoma cells.
AB  - 5-Aminolevulinic acid (ALA) is a precursor to heme synthesis pathway and
      currently used to induce endogenous protoporphyrin IX (PpIX, a potent
      photosensitizer) for photodynamic therapy of cancer. ALA has, however, a limited
      ability to cross cellular membranes due to its low lipid solubility. The use of
      lipophilic ALA esters may increase cellular uptake, which results in an enhanced
      PpIX synthesis. In the present study, a comparison of ALA and its hexyl ester (He
      ALA) was made in the QGY human hepatoma cell line with respect to PpIX production
      and its photocytotoxicity. The fluorescence emission spectrum of the cells
      incubated with He-ALA was identical to that of PpIX, indicating that He-ALA could
      induce PpIX in the cells. Fluorescence images demonstrated that the He-ALA
      induced PpIX was localized in the cytoplasm of the cells. Moreover, a similar
      amount of Pp IX was found in the cells incubated with 0.2 mmol/L He-ALA or 2
      mmol/L ALA and a similar level of cell survival was reached following light
      exposure. These results suggest that He-ALA is much more efficient at producing
      PpIX and photocytotoxicity than ALA itself in the cells.

PMID- 12198572
TI  - Molecular cloning and characterization of human DDX36 and mouse Ddx36 genes, new
      members of the DEAD/H box superfamily.
AB  - With the strategy of homologue molecular cloning using the sequence of the
      maleless gene (mle) of Drosophila, the novel homologous human and mouse genes
      with longer DNA/RNA helicase box (DEAD/DEAH box), named DDX36 and Ddx36 genes,
      respectively, were cloned as new members of the DEAD/H box superfamily. The
      predicted protein encoded by human DDX36 gene has a sequence identity of 37% and
      similarity of 58% with the MLE protein of Drosophila and 91% and 94% with the
      predicted protein encoded by mouse Ddx36 gene, respectively. Northern blotting of
      DDX36 shows a single strong signal of 3.8 kb in the hybridization pattern in
      human testis but no or very weak signal in other tissues. The DDX36 gene is
      mapped to chromosome 3q25.1-3q25.2, in which 26 exons and 25 introns have been
      identified. DDX36 and Ddx36 genes may be involved in sex development,
      spermatogenesis and male reproduction.

PMID- 12198573
TI  - The assignment of the reactive sites of the double-headed arrowhead proteinase
      inhibitor A and B.
AB  - The arrowhead proteinase inhibitor A and B (APIA and APIB) are double-headed and
      multifunctional. Both their primary structure and cDNA sequence have been
      elucidated. To locate the possible reactive site residues Lys(44), Arg(76) and
      Arg(87) of APIB predicted according to the sequence comparison with other
      proteinase inhibitors, the above residues were substituted with Pro by site
      directed mutagenesis respectively, and the mutated genes were expressed in the
      yeast secretion system. The mutant K(44)P-APIB displayed the same inhibitory
      activity as APIB does, while the mutants R(76)P-APIB and R(87)P-APIB could only
      inhibit one molecule, instead of two molecules of trypsin, indicating that
      Arg(76) and Arg87 but not Lys(44) are the two reactive sites of APIB. In order to
      further confirm this result, more mutants of APIB (K(44)P-R(76)P-APIB, K(44)P
      R(87)P-APIB,  R(76)P-R(87)P-APIB) were designed, in each mutant only one of the
      three possible reactive sites remained unchanged. Both the mutants K(44)P-R(76)P
      APIB and K(44)P-R(87)P-APIB could only inhibit one molecule of trypsin, while
      R(76)P-R(87)P-APIB could no longer inhibit trypsin intensively, thus the residues
      Arg(76) and Arg(87) are definitely the reactive sites of APIB. Their K(i) were
      measured to be 0.39 nmol/L and 0.47 nmol/L, respectively. The mutant R(87)L-APIB
      lost about half activity towards trypsin but could inhibit one molecule of
      chymotrypsin as the wide type APIA did, indicating that Leu(87) was the reactive
      site towards trypsin but could inhibit one molecule of APIA for inhibiting
      chymotrypsin.

PMID- 12198574
TI  - [Identification of a snoRNA47 gene cluster in Oryza sativa].
AB  - Small nucleolar RNAs (snoRNAs) are required for ribose 2'-O-methylation of
      eukaryotic ribosomal RNA. By researching in international rice genome databases,
      a snoRNA gene cluster, consisting of three box C/D snoRNA gene candidates, was
      found on chromosome 6. All of snoRNA coding sequences in this cluster exhibited
      the characteristic structure of box C/D antisense snoRNA. They shared conserved
      box C and box D motifs, a stable terminal stem formed by a 4-6 nt-long inverted
      repetition sequence located upstream of box C and downstream of box D. All
      candidates had a 12 nt-long sequence complementary to the region from 621 nt to 6
      32 nt in rice 18 S rRNA (nt numbering according to GenBank accession No. X00755),
      and might mediate the ribose 2'-O-methylation of A(623) in rice 18 S rRNA.
      Comparison of these sequences showed that these three rice snoRNAs were homologue
      of yeast snR47. These three rice snoRNAs were named as OSsnR47.1, OSsnR47.2 and
      OSsnR47.3, respectively. Primer extension assay showed that these three snoRNAs
      were transcribed in vivo and determined the 5' ends of each snoRNA. RT-PCR
      detected transcripts containing linked snoRNA47s and this suggested that the
      snoRNAs encoded in the cluster might be transcribed as a polycistronic transcript
      under the control of a single upstream promoter. The gene sequences encoding
      these three snoRNAs had been deposited in GenBank under accession number of
      AF453504  AF453503 an d AF453502.

PMID- 12198575
TI  - [Preparation of polyacrylamide gel electrophoresis for human chorionic
      gonadotropin chimeric peptide 12 expressed in E. coli].
AB  - In recent years, development of chimeric peptide (CP) immunogens is a trend in
      the vaccinological field. The CPs contain a B cell epitope(s) of target antigen
      and a promiscuous self - or foreign- T cell epitope(s). However, such constructed
      CPs were all expressed in prokaryotic or eukaryotic systems at lower levels. To
      purify the human chorionic gonadotropin (hCG) CP12 expressed in E. coli at the
      level of about 1% of the total cell proteins, an improved method of preparative
      gel polyacrylamide gel electrophoresis (PAGE) was developed. The important
      improvement to routine preparative PAGE involves: (1) running reversed
      electrophoresis by rearranging the gel- carrying plate when the bromophenol blue
      band arrived at 1-1.5 centimeter from the bottom of the gel; (2) making a
      collecting trough between the gel and a dialytic membrane that was used to
      isolate the upper tank buffer. About 8 fractions were collected at regular
      intervals of 15 minutes after bromophenol blue running out of gel. And then 0.2
      ml was taken from each fraction and the protein was precipitated by sequentially
      adding trichloroacetic acid and acetone. Each sample was dissolved in 20 microL
      sample buffer and analyzed and identified by SDS-PAGE and Western blotting. As a
      result, the hCG CP12 expression product with 95% relative homogeneity was
      harvested at a 50-100 microgram level after a single-step purification of this
      preparative PAGE, with respect to the sample which contained 3-4 mg of cell
      proteins.

PMID- 12198576
TI  - [Expression, refolding and biological activity of recombinant type-I
      metalloproteinase acutolysin a from Agkistrodon acutus].
AB  - Type-I snake venom metalloproteinase acutolysin A gene was cloned into the
      prokaryotic expression vector pBAD/gIIIA and the resulting recombinant plasmid
      pDS was obtained. By the induction with 0.02% L-(+)-arabinose, the recombinant
      metalloproteinase was expressed in insoluble inclusion body in E. coli TOP10 and
      reached up to 5%--10% of total bacterial proteins. The recombinant
      metalloproteinase has an additional sequence of N-terminal 22 amino acids and C
      terminal 8 amino acids (housing 6 histidines), both of which derived from the
      vector. The purified inclusion body was solubilized by 8 mol/L urea or 6 mol/L
      guanidine-HCl and the denatured soluble recombinant metalloproteinase was allowed
      to refold in vitro. Western blotting and ELISA obviously showed that the
      renatured recombinant metalloproteinase possessed strong immune reactivity very
      closely related to natural acutolysin A. Animal experiments showed that the
      refolded recombinant metalloproteinase had an obvious hemorrhagic activity.
      Except PMSF, 1 mmol/L EDTA, 1 mmol/L EGTA, and 3 mmol/L imidazole could inhibit
      the hemorrhagic activity of the recombinant and the natural metalloproteinases to
      different extent. Based on the investigations of others and our experimental
      results, the hemorrhagic mechanism of snake metalloproteinases was discussed.

PMID- 12198577
TI  - Epithelioid gastrointestinal stromal tumor of the stomach with liver metastases
      in a 12-year-old girl: aspiration cytology and molecular study.
AB  - Gastrointestinal stromal tumor (GIST), a stromal tumor of the gastrointestinal
      tract defined as CD117 (c-kit)-positive neoplasm, occurs primarily in adults.
      GIST with CD117 (c-kit) mutation and certain cytogenetic abnormalities is
      associated with malignancy, though a definite relationship between prognosis and
      molecular alterations remains to be elucidated. We report the cytologic features
      of an epithelioid GIST arising in the stomach of a child and metastatic to the
      liver, and the molecular mutational analysis of both the primary gastric tumor
      and the liver metastasis. Literature of pediatric GISTs was also reviewed. Fine
      needle aspiration of the liver metastasis, processed by Ultrafast Papanicolaou
      stain, showed fragments of cohesive small epithelioid cells with bland oval
      nuclei and unipolar cytoplasm transected by capillaries. Immunohistochemically,
      all nodules in the stomach and liver expressed CD117 (c-kit). Interestingly, some
      of the gastric tumor clusters were uniformly CD34 positive, whereas others were
      uniformly CD34 negative, suggesting heterogeneity of tumor clones. The presence
      of neurosecretory granules further subtyped the tumor into gastric autonomic
      nerve tumor (GANT). Molecular mutational analysis, performed in both the gastric
      tumor and the liver metastasis, showed no sequence abnormality in exons 9, 11,
      and 13 of CD117 (c-kit). Cytogenetic study revealed normal karyotype. These
      features might suggest a different molecular mechanism leading to malignancy in
      certain GISTs arising in children.

PMID- 12198578
TI  - Biological monitoring of midwives' exposure to N(2)O using the Bio-VOC breath
      sampler.
AB  - The use of exhaled breath as a biological monitoring tool is still not widely
      used. Although there are now commercially available kits, there are limited data
      on biological guidance values for all but a few substances for breath monitoring.
      The study investigated the possibility of using an indirect breath sampler to
      measure the levels of nitrous oxide in the exhaled breath of midwives at a
      midpoint during their shift. Levels of nitrous oxide in the exhaled breath were
      measured at (0-727 ppm) with a mean level of 64 ppm. The correlation between the
      established personal environmental monitoring and exhaled breath monitoring was
      generally poor as was the correlation between duration of nitrous oxide exposure
      and levels in the exhaled breath. Clearly the use of exhaled breath as a tool for
      biological monitoring is more appropriate than other invasive procedures. The
      breath sampler used has been a readily acceptable tool for occupational hygiene
      monitoring in a busy hospital ward.

PMID- 12198579
TI  - Accuracy of self-reported pesticide use duration information from licensed
      pesticide applicators in the Agricultural Health Study.
AB  - Epidemiologists frequently rely on self-reported information regarding a variety
      of exposures including smoking history, medication use, and occupational exposure
      because other sources of information are either unavailable or difficult to
      obtain. One way to evaluate the accuracy of self-reported information is through
      logic checks using other sources. To assess the quality of the self-reported
      pesticide product use history of 57,311 licensed pesticide applicators in the
      Agricultural Health Study (AHS), we compared the self-reported decade of first
      use and total years of use to the year the pesticide active ingredient was first
      registered for use. We obtained pesticide active ingredient registration
      information from the United States Environmental Protection Agency (USEPA) and
      other publicly available sources for the 52 pesticides on the AHS initial
      questionnaires administered from 1994 to 1997. Based on the registration year, we
      assessed 19 pesticides for potential inaccuracies regarding duration of use or
      decade of first use. When calculating potential total years of use, we did not
      consider the impact of chemicals being removed from the market, since the
      possibility for continued use existed. The majority of respondents provided
      plausible responses for both decade of first use and total duration of use. On
      average, 1% of the subjects overestimated total possible duration of use, ranging
      from less than 1% for carbofuran and chlorpyrifos to 5% for imazethapyr. Decade
      of first use was also reasonably reported, although more subjects did not report
      decade of first use than duration of use, with an average of 6% of subjects
      missing decade information for an individual chemical. For subjects who reported
      a decade of first use, 98% gave plausible responses on average, with
      overestimates highest for cyanazine, introduced in 1971 (6% reported earlier
      use), and chlorimuron ethyl, introduced in 1985 (7% reported earlier use). This
      analysis provided the opportunity to consider only one source of potential
      overreporting of exposure, and while underreporting may have also occurred, we
      cannot evaluate its role nor the balance between these potential inaccuracies.
      While we are unable to validate directly the accuracy of a respondent's use of
      pesticides, this analysis suggests that participants provide plausible
      information regarding their pesticide use.

PMID- 12198580
TI  - Temporal trends in human TCDD body burden: decreases over three decades and
      implications for exposure levels.
AB  - Data on lipid levels of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) in the general
      population in the United States, Canada, Germany, and France over the past 30
      years were compiled from the literature. Mean lipid levels of TCDD exhibited a
      steady decrease by nearly a factor of 10 over this time period, with lipid
      adjusted TCDD levels in 2000 about 2 parts per trillion (ppt). Pharmacokinetic
      modeling using a one-compartment model indicated that absorbed intake levels of
      TCDD must have decreased by more than 95% from levels in 1972 to result in the
      observed decrease in human lipid levels, with the bulk of this decrease occurring
      before 1980. Based on this modeling and the pharmacokinetic properties of TCDD in
      humans, we conclude that mean levels of TCDD in the general population are likely
      to decrease further over the next 15 years, to between 0.5 and 1 ppt, even if
      intake levels do not decrease further. Fewer data over a shorter time period are
      available for other dioxin and furan congeners in human lipid, but these data
      indicate substantial decreases as well, with general population TEQ lipid levels
      currently at least fourfold lower than in 1970 and still decreasing. Food
      sampling data are limited, but support these trends.

PMID- 12198581
TI  - Sampling private wells at past homes to estimate arsenic exposure: a methodologic
      study in New England.
AB  - We are conducting a collaborative, population-based case-control study in Maine,
      New Hampshire, and Vermont to investigate the reasons for the elevated bladder
      cancer mortality in northern New England. Arsenic in drinking water is one of the
      primary exposures under investigation. To estimate subjects' lifetime exposure to
      waterborne arsenic, it will be necessary to obtain water samples from private
      wells that subjects used in the past. We conducted a methodologic study to assess
      the feasibility of locating and sampling from private wells at subjects' past
      residences. Ninety-eight New Hampshire residents (mean age 67 years) completed a
      questionnaire requesting the complete address, dates of occupancy, and drinking
      water sources for each home lived in since birth. An interviewer then asked
      subjects for more detailed information about each home to assist in a field
      search of past homes in the three-state study area of Maine, New Hampshire, and
      Vermont. Fifty-eight of the 98 subjects indicated that they had used a total of
      103 private wells in 95 previous homes located in these three states. We
      conducted a field search to locate these 95 homes, visited town offices to find
      the properties on tax maps and obtain the current owners' names and addresses,
      attempted to obtain permission from the current owners to sample the wells, and
      collected water samples. In all, 48 (47%) of the 103 past wells in the study area
      were sampled successfully. The remaining wells were not sampled because the homes
      were not located (22%) or had been demolished (2%), permission to sample the
      wells was not obtained (17%), the wells had been destroyed (7%) or could not be
      found on the grounds of the residence (3%), or for other reasons (2%). Various
      approaches for improving the success rates for sampling water from private wells
      are discussed, as is the use of predictive modeling to impute exposures when
      sampling is not feasible.

PMID- 12198582
TI  - A longitudinal study of mortality and air pollution for Sao Paulo, Brazil.
AB  - We study the effects of various air-pollution variables on the daily death counts
      for people over 65 years in Sao Paulo, Brazil, from 1991 to 1993, controlling for
      meteorological variables. We use a state space model where the air-pollution
      variables enter via the latent process, and the meteorological variables via the
      observation equation. The latent process represents the potential mortality due
      to air pollution, and is estimated by Kalman filter techniques. The effect of air
      pollution on mortality is found to be a function of the variation in the sulphur
      dioxide level for the previous 3 days, whereas the other air-pollution variables
      (total suspended particulates, nitrogen dioxide, carbon monoxide, ozone) are not
      significant when sulphur dioxide is in the equation. There are significant
      effects of humidity and up to lag 3 of temperature, and a significant seasonal
      variation.

PMID- 12198583
TI  - Glass-based radon-exposure assessment and lung cancer risk.
AB  - Lung cancer risk estimation in relation to residential radon exposure remains
      uncertain, partly as a result of imprecision in air-based retrospective radon
      exposure assessment in epidemiological studies. A recently developed methodology
      provides estimates for past radon concentrations and involves measurement of the
      surface activity of a glass object that has been in a subject's dwellings through
      the period for exposure assessment. Such glass measurements were performed for
      110 lung cancer subjects, diagnosed 1985 to 1995, and for 231 control subjects,
      recruited in a case-control study of residential radon and lung cancer among
      never-smokers in Sweden. The relative risks (with 95% confidence intervals) of
      lung cancer in relation to categories of surface-based average domestic radon
      concentration during three decades, delimited by cutpoints at 50, 80, and 140 Bq
      m(-3), were 1.60 (0.8 to 3.4), 1.96 (0.9 to 4.2), and 2.20 (0.9 to 5.6),
      respectively, with average radon concentrations below 50 Bq m(-3) used as
      reference category, and with adjustment for other risk factors. These relative
      risks, and the excess relative risk (ERR) of 75% (-4% to 430%) per 100 Bq m(-3)
      obtained when using a continuous variable for surface-based average radon
      concentration estimates, were about twice the size of the corresponding relative
      risks obtained among these subjects when using air-based average radon
      concentration estimates. This suggests that surface-based estimates may provide a
      more relevant exposure proxy than air-based estimates for relating past radon
      exposure to lung cancer risk.

PMID- 12198584
TI  - Risks to the public from historical releases of radionuclides and chemicals at
      the Rocky Flats Environmental Technology Site.
AB  - This paper summarizes the methods and results of estimating risks of cancer
      incidence resulting from plutonium, carbon tetrachloride, and beryllium releases
      from operations at the Rocky Flats Environmental Technology Site, near Denver,
      Colorado, from 1953 through 1989. The key findings show that people who lived
      near the facility were exposed to plutonium mainly through inhalation during
      routine operations, from a major fire in 1957, and from plutonium resuspended
      from contaminated soil from an outdoor drum storage area, called the 903 Area.
      Results were presented for five exposure scenarios that were location
      independent. Individuals described by the laborer scenario received the highest
      risk of all scenarios considered. Upper bound (95th percentile) incremental
      lifetime cancer incidence risks for the laborer scenario were in about the 10(-4)
      range (1 chance in 10,000) for developing cancer from Rocky Flats plutonium
      releases during a lifetime. At the 5th percentile level, the maximum cancer risk
      was about 10(-7) (1 chance in 10 million) for developing cancer during a
      lifetime. Estimated cancer risks at the 95th percentile level are within the
      range of for acceptable risks established by the US Environmental Protection
      Agency of 10(-6) to 10(-4). Carbon tetrachloride was found to be the chemical
      that presented the highest risk to the public. The 5th and 95th percentile risk
      values for exposure to carbon tetrachloride were 9.2x10(-7) and 2.5x10(-5),
      respectively.

PMID- 12198585
TI  - Questionnaire assessment of nonoccupational pesticide exposure in epidemiologic
      studies of cancer.
AB  - Pesticides have been examined in epidemiologic studies as environmental risk
      factors for cancer, in part, due to the identification of carcinogenic properties
      of some of these chemicals using animal models. Although the majority of these
      epidemiologic studies have focused on occupational pesticide exposure,
      nonoccupational pesticide exposure has also been investigated. The objective of
      this paper is to review the methodological issues of nonoccupational pesticide
      exposure assessment, including identifying the methods that have been used to
      assess self-reported nonoccupational pesticide exposure in epidemiologic studies
      of cancer, and discussing the strengths and limitations of the current
      methodology as well as possible enhancements that could be incorporated into
      future investigations. Issues of exposure assessment that will be reviewed
      include specificity, recall, and characteristics of pesticide exposure.
      Additionally, sources of nonoccupational pesticide exposure other than
      residential will be briefly reviewed.

PMID- 12198586
TI  - Investigation of deaths in an area of groundnut plantations in Casamance, South
      of Senegal after exposure to Carbofuran, Thiram and Benomyl.
AB  - Between May and October 2000, the Regional Health Office of Kolda Region in the
      south of Senegal, West Africa, reported an epidemic of an unknown illness
      characterized by thoracic pain, dyspnea and edemas of limb and face. The epidemic
      covered a radius of approximately 40 km (24 miles) between the districts of Kolda
      and Sedhiou in Kolda Region. Cases were mostly men whose age ranged between 12
      and 60 years old. Investigation revealed that they had been exposed to pesticides
      distributed by the government to groundnut farmers. The signs and symptoms
      suggested intoxication with carbamates, carbofurans, and possibly thiram,
      contained in the pesticides distributed with the groundnut seeds. Government
      distribution created an excessive use of pesticides in the farms, and
      consequently an overexposure of the subjects who handled the seeders, especially
      young males but also a small proportion of women who worked in the groundnut
      fields. Many of these subjects, not accustomed to handle pesticides, came to
      overestimate the quantity of product to fill the seeder. It should be noted that
      the policy of distribution of pesticides in Senegal, which presents risk of
      poisoning, was not systematically accompanied by sufficient information on the
      danger of the products and of certain precautions that should be taken during
      their use.

PMID- 12198588
TI  - [Prevention of pre-eclampsia by low-dose acetylsalicylic acid--a critical
      appraisal].
AB  - Pre-eclampsia has been shown to be associated with platelet activation and
      excessive release of vasoconstricting thromboxane preceding the onset of the
      disease. Low-dose acetylsalicylic acid (ASA) substantially inhibits thromboxane
      formation and may thus prevent pre-eclampsia from developing. In agreement with
      this hypothesis early randomised trials reported on promising reductions in pre
      eclampsia risk and possible fetal growth retardation. Subsequent multicentre
      trials during the nineties failed to confirm a large benefit, which may in part
      be explained by late initiation of treatment, low dosages, low patient compliance
      and wide inclusion of women with concomitant disorders such as chronic
      hypertension, diabetes mellitus and kidney disease. A recent systematic review of
      all randomised trials showed an acceptable safety profile and a significant but
      only moderate reduction in the risk of pre-eclampsia regardless of gestation at
      trial entry or dose of ASA. There is now growing evidence that the earlier ASA
      treatment is started, the greater the reduction in the risk of pre-eclampsia is.
      Moreover, ASA has much stronger effects at higher (80 - 150 mg/day) than at lower
      doses in the protection against pre-eclampsia and the prevention of severe fetal
      growth retardation. No clinically important effects, however, have been found in
      patients with chronic hypertension, kidney disease or diabetes mellitus. In
      contrast, low dose ASA (100 mg/day) might benefit women with unfavourable
      obstetric history, in particular those with severe fetal growth retardation or
      pre-eclampsia with onset at < 32 weeks. The crucial time for starting treatment
      may be before 16 weeks and daily ingestion before bedtime appears useful. To
      start low-dose ASA at 20 - 24 weeks gestation seems only justified in women with
      abnormal uterine Doppler flow.

PMID- 12198589
TI  - [Syphilis in pregnancy].
AB  - Syphilis, a sexually transmitted infection, has a major impact on the disease
      burden worldwide. Globally, an estimated 12 million new cases of sexually
      acquired syphilis occurred in 1997. Developing countries in Africa, Southeast
      Asia and regions of the former Soviet Union are mainly affected. With rising
      numbers of human immunodeficiency virus-infected pregnant women and an increase
      in gonorrhoea in some areas, the incidence of syphilis is expected to increase
      again. As a consequence of migration from Eastern bloc countries to Europe after
      the breakdown of the former Soviet Union, the resurgence of syphilis will also
      affect Germany. Therefore, we present the clinical picture of syphilis as well as
      review the current recommendations of the German STD Society, the Centers of
      Disease Control (CDC), USA, and the Clinical Effectiveness Group (CEG), England,
      for diagnosis and treatment of syphilis with special emphasis on pregnancy.
      Considering the current epidemiological situation, physicians should include
      syphilis in their differential diagnosis. Although recommended therapy regimens
      differ, penicillin is the treatment of choice. Pregnant patients who are allergic
      to penicillin should be desensitized and treated with penicillin. Early
      recognition and timely treatment of syphilis are essential to prevent or treat
      potentially fatal fetal infection.

PMID- 12198590
TI  - [Associations between birth weight and placental volume in the first trimester].
AB  - INTRODUCTION: Associations between the size of the placenta and birth weight have
      been described before. This connection has also been found in (sonographically
      estimated) second trimester placental size. The aim of this study was to find out
      if there are any differences in first trimester placental volume between various
      birth weight groups. METHODS: Placental volume was obtained from non-smoking
      women at the end of the first trimester during a period of eight months. After
      birth, the newborns were divided into four groups: below the 10th, 10th to 50th
      50th to 90th and above the 90th centile. As is known from previous research,
      placenta size changes in proportion to crown-rump-length. Therefore, the medians
      of the "placenta quotients" (placental volume/CRL) of each group were compared in
      order to correct for differences in gestational age. RESULTS: Data from 1476
      pregnancies could be evaluated. The overall median of the placenta quotient was
      0.98. It was 0.85 in the group below the 10th, 0.92 between 10th and 50th, 1.02
      between 50th and 90th and 1.10 above the 90th centile (p < 0.0001, median test).
      DISCUSSION: The finding of associations between early pregnancy placental size
      and birth weight at term gives hope for the development of new diagnostic methods
      for the recognition of placenta-associated problems. Further research is required
      to estimate the clinical possibilities for the detection of pregnancies at risk
      of severe growth retardation and other conditions.

PMID- 12198591
TI  - [Neonatal ultrasonographic cerebral findings: association with risk factor for
      cerebral palsy].
AB  - BACKGROUND: Is it possible to identify patients with cerebral palsy (CP) with
      postnatal ultrasound scan? Which risk factors are associated with an increased
      risk of CP?. PATIENTS AND METHODS: The data of 37 children with CP, who were
      sonographically investigated during the first 24 hours of life were analyzed
      retrospectively. The data of 21 preterm infants with gestational age </= 32 wk
      were compared with the data of 59 without CP. RESULTS: A tetraparesis was found
      in 15/21 of preterm babies </= 32 wk, a hemiparesis in 4/8 of premature infants
      >/= 33 wk and in 5/8 of the mature babies. The mature babies had prenatal brain
      atrophy or hypoxic-ischaemic cerebral lesions. Cytomegaly and encephalitis were
      detected in two babies. Immature babies >/= 33 wk showed prenatal porencephaly or
      encephalomalacia after asphyxia. Premature babies </= 32 wk had cystic
      periventricular leucomalacia (n=12) or cerebral haemorrhage (n=3); 3 babies had
      meningitis. Only two prematures </= 32 wk with mild CP had inconspicuous
      ultrasound scans. Factors associated with cerebral palsy were: cystic
      periventricular leucomalacia (OR 24,89; 95 % CI: 5,85 - 105,87), cerebral atrophy
      (OR 4,84; 95 % CI: 1,61 - 14,51), fetal hypoxia (CTG) - (OR 4,78; 95 % CI: 1,31 -
      17,45), abruptio placentae (OR 4,32; 95 % CI: 1,16 - 16,13), anemia after birth
      (OR 18,13; 95 % CI: 1,97 - 166,43), abnormal neurological behavior at term (OR
      14,00; 95 % CI: 3,29 - 59,55). CONCLUSION: Cerebral ultrasound scan after birth
      is a useful method detect for cerebral lesions in patients with CP-risks.

PMID- 12198592
TI  - [Management of patients with Type 2B von Willebrand's disease during delivery and
      puerperium].
AB  - Von Willebrand's disease (VWD) is the most common congenital haemorrhagic
      diathesis inherited as an autosomal dominant trait, with a prevalence estimated
      to be 1 - 2 %. In subtype 2B an abnormally structured von-Willebrand factor (VWF)
      leads to an increased binding of VWF molecules to normal platelets, which
      regularly results in thrombocytopenia in pregnancy. Only few systematic
      observations in patients with type 2B VWD in the perinatal period have been
      reported in the literature. Six spontaneous deliveries in two sisters with type
      2B VWD are reported. The first patient did not show any bleeding complications in
      five vaginal deliveries without any factor replacement therapy. The second
      patient showed a massive haemorrhage on the third postpartum day after
      administration of factor VIII-VWF concentrate replacement therapy (Haemate(R)
      HS), only on the day of delivery. No neonatal complications were reported. The
      clinical management of pregnancy, delivery and puerperium in patients with type
      2B VWD requires close collaboration of experienced obstetricians, haematologists,
      anaesthesiologists and paediatricians. During labour and delivery, but especially
      in puerperium, there is a significantly increased risk for haemorrhage. Vaginal
      delivery is generally safe, but the incidence of postpartum haemorrhage is 30 %.
      These bleedings may be extremely severe. The danger of postpartum bleeding
      complications cannot be predicted with certainty, neither by past history of
      bleeding episodes or haematological laboratory tests of VWF activity levels.
      Hence, in all patients factor VIII-VWF concentrate replacement therapy should be
      initiated already in the first stage of labour. Post partum replacement therapy
      along with effective uterotonic therapy should be continued at least for seven
      days. With this treatment bleeding problems may be largely prevented. The
      decision to perform epidural block in labour and delivery must be assessed
      depending on individual risk factors.

PMID- 12198593
TI  - [Ovarian hyperstimulation syndrome in preterm infants].
AB  - Ovarian cysts are a relatively frequent finding in fetuses and neonates. In
      preterm infants, a simultaneous occurrence of estradiol-producing ovarian cysts
      and edematous swelling of the vulva, the thighs and the lower abdominal wall was
      described by Sedin and co-workers in 1985 for the first time. This ovarian
      hyperstimulation syndrome occurred at a postconceptional age that slightly
      preceded the expected time of delivery. We report on four extremely low birth
      weight infants who were observed in the neonatal ward with ovarian cysts and
      stimulation of the external and internal genitalia, beginning at a
      postconceptional age of 35 to 39 weeks. The serum concentration of estradiol was
      within or above the range of the preovulatory peak of adults in all patients.
      Other causes of edema in preterm infants were excluded. The findings receded
      during 5 - 9 weeks. It is supposed, that in some cases the physiologically high
      concentration of gonadotropins in preterm infants stimulates the ovaries to
      produce ovarian cysts as well as to secrete high amounts of estradiol. This
      induces a transient stimulation of the external and internal genitalia as in
      idiopathic or transient precocious puberty.

PMID- 12198594
TI  - [Newborn with phocomelia and thrombocytopenia. Case report].
AB  - Associated malformations and symptoms may be decisive in the differential
      diagnosis of neonatal phocomelia. We report on a neonate with phocomelia,
      petechiae and thrombocytopenia. This constellation is typical for the phocomelia
      thrombocytopenia-syndrome, a variant of the thrombocytopenia-absent radius-(TAR)
      syndrome. During the neonatal period platelet transfusions were necessary.
      Relevant bleeding and development delays were not evident until the age of seven
      months. Cardinal symptoms of the TAR syndrome are bilaterally absent radius and
      neonatal thrombocytopenia. The patient presented with phocomelia of the upper
      extremities which occurs in only 5 - 10 % of the patients with TAR syndrome.
      Further abnormalities include additional bone and joint disorders and
      haematopoietic problems, such as thrombocytopenia. Bleeding episodes mainly occur
      in the first year of life, hence platelet transfusions may be necessary during
      this period. A new experimental approach is the Interleukin-6-mediated
      stimulation of thrombopoiesis. Usually platelet counts reach normal values in
      adults. The main problem remains a satisfactory management of various limb
      defects.

PMID- 12198596
TI  - Transcriptional suppression of the estrogen receptor by truncated estrogen
      receptor-alpha.
AB  - The estrogen receptor (ER) is composed of six major functional domains - the A/B
      domain as the activation function 1 domain, domain C as the DNA-binding domain,
      domain D as a hinge domain, and domain E/F as the ligand-dependent
      transcriptional domains. A novel protein (designated as SRB-RGS) that interacted
      with domains C and D of ER alpha (ER alpha C/D) repressed the transcriptional
      activity of ER alpha. In this study, we have examined whether ER alpha C/D
      releases transcriptional suppression of ER alpha by intrinsic SRB-RGS. The
      expression vector of ER alpha C/D was transfected to the human cancer cell, KPL
      1, which expressed the intrinsic ER. Unexpectedly, transcriptional suppression of
      ER by ER alpha C/D was observed. COS-7 cells, which have no intrinsic ER, showed
      a similar suppression of ER alpha by co-transfection of ER alpha and ER alpha
      C/D. The DNA-binding and the estrogen-binding activities of ER alpha decreased on
      co-transfection of ER alpha C/D, suggesting a decrease in the receptor protein
      itself. It is likely that the degradation of ER by co-transfection caused the
      transcriptional suppression of the ER.

PMID- 12198595
TI  - Testosterone and prolactin regulation of metabolic genes and citrate metabolism
      of prostate epithelial cells.
AB  - The control and alteration of key regulatory enzymes is a determinant of the
      reactions and pathways of intermediary metabolism in mammalian cells. An
      important mechanism in the metabolic control is the hormonal regulation of the
      genes associated with the transcription and the biosynthesis of these key
      enzymes. The secretory epithelial cells of the prostate gland of humans and other
      animals possess a unique citrate-related metabolic pathway regulated by
      testosterone and prolactin. This specialized hormone-regulated metabolic activity
      is responsible for the major prostate function of the production and secretion of
      extraordinarily high levels of citrate. The key regulatory enzymes directly
      associated with citrate production in the prostate cells are mitochondrial
      aspartate aminotransferase, pyruvate dehydrogenase, and mitochondrial aconitase.
      Testosterone and prolactin are involved in the regulation of the corresponding
      genes associated with these enzymes (which we refer to as "metabolic genes"). The
      regulatory regions of these genes contain the necessary response elements that
      confer the ability of both hormones to control gene transcription. In this
      report, we describe the role of protein kinase c (PKC) as the signaling pathway
      for the prolactin regulation of the metabolic genes in prostate cells.
      Testosterone and prolactin regulation of these metabolic genes (which are
      constitutively expressed in all mammalian cells) is specific for these citrate
      producing cells. We hope that this review will provide a strong basis for future
      studies regarding the hormonal regulation of citrate-related intermediary
      metabolism. Most importantly, altered citrate metabolism is a persistent
      distinguishing characteristic (decreased citrate production) of prostate cancer
      (PCa) and also (increased citrate production) of benign prostatic hyperplasia
      (BPH). An understanding of the role of hormonal regulation of metabolism is
      essential to understanding the pathogenesis of prostate disease. The
      relationships described for the regulation of prostate cell metabolism provides
      insight into the mechanisms of hormonal regulation of mammalian cells in general.

PMID- 12198597
TI  - Effects of dietary cholesterol on pyroglutamyl aminopeptidase activity in mouse
      frontal cortex, pituitary, and adrenal glands.
AB  - Pyroglutamyl aminopeptidase (pGluAP) is an omega peptidase that hydrolyzes
      biologically active peptides, such as thyrotropin-releasing hormone (TRH), with
      neuronal and extraendocrine functions. We analyzed the effects of a cholesterol
      enriched diet on soluble and membrane-bound pGluAP activity in frontal cortex,
      pituitary and adrenal glands of male and female mice using fluorimetric assays.
      Significant increases were observed in soluble pGluAP activity in the frontal
      cortex and adrenal glands in males and in the pituitary in females. Membrane
      bound pGluAP activity was increased in the frontal cortex and pituitary of males
      and females after the mice were fed a cholesterol-enriched diet. These increases
      may produce changes in the metabolism of endogenous substrates, including TRH,
      which may be related to alterations in its neuromodulator functions and to the
      possible relationship between TRH and other neurotransmitter systems.

PMID- 12198598
TI  - Varying additive effects of bromocriptine with two somatostatin analogs in
      cultures of GH-secreting adenomas.
AB  - In this study, we have investigated the effect of combined treatment using two
      somatostatin analogs, lanreotide or octreotide, with bromocriptine on GH release
      in cultures of GH-secreting pituitary tumors. Sixteen acromegalic patients were
      included in the study. All patients had been treated with lanreotide prior to the
      surgery. Five patients (31.2 %) reached GH levels below 2.0 microg/l and normal
      IGF-I levels according to age and sex after lanreotide treatment. A positive
      correlation was observed between the lanreotide-induced inhibition of GH release
      in vitro and serum GH decrease after lanreotide treatment (r = 0.52; p = 0.03).
      Combined treatment significantly inhibited GH release in vitro in 8 of the 16
      tumors (50 %). However, only 5 (31.2 %) of the respective patients had been
      resistant to presurgical treatment with lanreotide. Three of these 5 patients
      (18.7 %) responded to a BC concentration similar to that achieved with
      therapeutic doses, and in 2 patients only when a pharmacological dose of BC was
      used in the combined treatment. The additive effect was observed with the
      combination of lanreotide and BC in 6 tumors and with octreotide and BC in 3.
      Only one tumor showed simultaneous response to both types of combination. These
      results suggest that the additive effect under the combined treatment might be
      found between 18 and 30 % of patients who are resistant to these drugs, and that
      different combinations of somatostatin analogs and dopamine agonists should be
      tested in resistant patients.

PMID- 12198599
TI  - Stimulatory effects of LH on release of melatonin and activities of its
      synthesizing enzymes NAT and HIOMT in organ-cultured pineal glands of female
      rats.
AB  - The pineal hormone melatonin (N-acetyl-5-methoxytryptamine) exerts
      antigonadotropic effects in some mammalian species. To evaluate the effect of
      luteinizing hormone (LH) on melatonin release and its synthesizing enzyme
      activities in pineal glands, pineals of adult female rats undergoing diestrus
      were organ-cultured in a medium containing 10(-12), 10(-10) or 10(-8) M LH for 6
      h. Melatonin release increased significantly in pineals cultured with 10(-12) and
      10(-10) M LH, as compared to control values. Similarly, the activity of
      arylalkylamine N-acetyltransferase (NAT), the key regulatory enzyme in melatonin
      biosynthesis, was significantly higher in pineals cultured with 10(-12) and 10(
      10) M LH for 6 h, while LH at 10(-8) M had no effect. Although LH at 10(-10) M
      increased pineal hydroxyindole-O-methyltransferase (HIOMT) activity, which
      catalyzes the final step of melatonin biosynthesis, LH at 10(-12) and 10(-8) M
      had no effect. These results demonstrate that at relatively low physiological
      levels, LH stimulates pineal melatonin synthesis and release, mainly by
      increasing NAT activity.

PMID- 12198600
TI  - The effects of surgically removing subcutaneous fat on the metabolic profile and
      insulin sensitivity in obese women after large-volume liposuction treatment.
AB  - The aim of this study was to identify the effects of surgically removing
      subcutaneous fat on the metabolic profile and insulin sensitivity in obese women
      after large-volume liposuction treatment. An open clinical trial with a non
      intervention parallel group was carried out on 12 young, obese women. After
      randomization, six volunteers were selected to the surgical intervention
      consisting of large-volume liposuction; the other six women were considered as
      the non-intervention group. Metabolic profiles and insulin tolerance tests to
      assess insulin sensitivity were performed on all volunteers before intervention
      or non-intervention and 21 - 28 days afterwards. There were a significant
      decrease in glucose (4.9 +/- 0.4 vs. 4.6 +/- 0.2 mmol/l, p < 0.05) and uric acid
      (250.8 +/- 56.2 vs. 224.0 +/- 53.4 micromol/l, p < 0.05) levels after
      liposuction; insulin sensitivity improved after the surgical intervention (4.3 +/
      0.9 vs. 5.3 +/- 0.8 %/min, p = 0.046). In conclusion, surgical removal of
      subcutaneous fat by large-volume liposuction led to an improvement in insulin
      sensitivity and a decrease in glucose and uric acid concentrations.

PMID- 12198601
TI  - Acceleration by fructose of the ATP-sensitive K(+) channel-independent pathway of
      glucose-induced insulin secretion.
AB  - The mechanism with which fructose augments glucose-induced insulin secretion is
      still unclear. The present study was aimed at examining whether the ketohexose
      potentiates the ATP-sensitive K(+) channel-independent pathway of glucose-induced
      insulin secretion and, if so, how this happens. When isolated rat islets were
      depolarized by incubating them with 50 mM KCl in the presence of 150 microM
      diazoxide (an opener of ATP-sensitive K(+) channels), 10 mM glucose plus 20 mM
      fructose elicited significantly higher insulin secretion than 10 mM glucose
      alone, whereas 20 mM fructose alone did not stimulate insulin secretion. The
      fructose 1,6-bisphosphate and inositol trisphosphate contents were markedly
      higher in islets incubated with glucose plus fructose than in islets incubated
      with glucose alone. The results demonstrate that fructose has the ability to
      potentiate the ATP-sensitive K(+) channel-independent pathway of glucose-induced
      insulin secretion. The increase in fructose 1,6-bisphosphate content induced by
      the co-presence of fructose with glucose, resulting in the rise in inositol
      trisphosphate content, is likely to be one of the signals involved in the
      fructose potentiation of glucose-induced insulin secretion.

PMID- 12198602
TI  - Antibodies to bovine beta-casein in diabetes and other autoimmune diseases.
AB  - Cow's milk is thought to be an environmental trigger for autoimmune response in
      Type 1 diabetes. In the present study, our aim was to investigate the antibody
      response to bovine beta-casein in different immune- and non-immune-mediated
      diseases and to establish whether such an antibody response is specific to Type 1
      diabetes. We measured antibodies to bovine beta-casein using an enzyme-linked
      immunosorbent assay in a total of 519 sera from subjects as follows: 71 patients
      with Type 1 diabetes, 33 patients with coeliac disease, 100 patients with latent
      autoimmune diabetes in adults (LADA), 50 patients with autoimmune thyroid disease
      (ATD), 50 patients with Type 2 diabetes, 24 patients with multiple sclerosis
      (MS), and 3 different groups of controls (n = 191). Significantly increased
      levels of antibodies to beta-casein were found in patients with Type 1 diabetes,
      coeliac disease and in LADA compared to age-matched controls (p = 0.01, p = 0.02
      and p = 0.01, respectively). No differences were observed in beta-casein antibody
      titres between patients with other disease conditions (MS, and ATD) and age
      matched controls. The highest antibody response to beta-casein in Type 1 diabetic
      patients and in patients with coeliac disease could reflect the gut mucosal
      immune disorders common to Type 1 diabetes and coeliac disease. Furthermore, the
      elevated beta-casein antibody levels found in LADA patients suggest that the
      antibody response to this protein may be relevant in autoimmune diabetes.

PMID- 12198603
TI  - High concentrations of procalcitonin but not mature calcitonin in normal human
      milk.
AB  - Procalcitonin (PCT) is one of the precursors in the synthesis of calcitonin in
      thyroidal C-cells and other neuroendocrine cells. PCT and other calcitonin
      precursors in serum are present at less than 50 pg/ml in healthy individuals, but
      are highly elevated in serum where conditions leading to systemic inflammatory
      response syndrome or sepsis prevail. We measured PCT concentrations in milk and
      serum samples taken from 9 healthy women after delivery. PCT concentrations were
      below 10 pg/ml in serum samples, but were more than 100 times as high in the
      corresponding milk samples. PCT in milk reached a maximum within the early days
      after delivery, with a median peak concentration of 2310 pg/ml (range 223 - 4224
      pg/ml) at day one and 2442 pg/ml (range 952 - 4488 pg/ml) at day two, then
      declining over the next days to a median concentration of 747 pg/ml (range 443 -
      1656 pg/ml) at day 10 (p = 0.012, by Friedman ANOVA). PCT values reached a steady
      state of 504 pg/ml median value. Mature calcitonin values measured in parallel
      with a specific assay were not above the normal range of 10 pg/ml in any samples
      measured. The strong discrepancy between serum and milk PCT suggests that PCT
      (but not mature calcitonin) is synthesised in the breast of healthy mothers after
      delivery. The precise mechanism and the physiological relevance are unclear.
      Since PCT levels increase drastically in serum from patients suffering from
      sepsis and related conditions, and since PCT has been ascribed a pro-inflammatory
      function, we propose that milk PCT might contribute to the activation of the
      developing neonatal immune system. Similar speculations were proposed for a
      variety of other pro-inflammatory cytokines, which had comparable kinetics in
      human milk.

PMID- 12198604
TI  - Concentration and composition of free ceramides in human plasma.

PMID- 12198605
TI  - Sexual history and Epstein-Barr virus infection.
AB  - To determine the role of sexual contact in transmission of Epstein-Barr virus
      (EBV) and occurrence of infectious mononucleosis (IM), a cross-sectional study
      was undertaken of EBV serologic testing and histories of IM and sexual behavior
      among 1006 new students at Edinburgh University. Prevalence of EBV seropositivity
      was significantly greater among women (79.2%) than among men (67.4%; P<.001) and
      among those who had ever been sexually active (82.7%) than among those who had
      not (63.7%; P<.001). Having a greater number of sex partners was a highly
      significant risk factor for EBV seropositivity. Two thirds of IM cases, but only
      a tenth of asymptomatic primary EBV infections, were statistically attributable
      to sexual intercourse. The findings suggest that EBV transmission occurs during
      sexual intercourse or closely associated behaviors. Transmission in this way
      appears to account for most cases of IM but for only a minority of cases of
      asymptomatic EBV infection, which mainly occur at younger ages.

PMID- 12198606
TI  - Risk factors for subsequent cervicovaginal human papillomavirus (HPV) infection
      and the protective role of antibodies to HPV-16 virus-like particles.
AB  - A high incidence of initial infection with human papillomavirus (HPV) was
      previously reported in a cohort of 608 women monitored at 6-month intervals for 3
      years. Risk factors for subsequent infections with different HPV types and
      whether antibodies against HPV-16 virus-like particles (VLPs) protected against
      these infections were examined. Subsequent infections with HPV are very common.
      Seventy percent of women acquired a different HPV type within 24 months of the
      initial infection. Risk factors included being nonwhite, having an increased
      number of male sex partners, and having had a new male sex partner. Use of oral
      contraceptive pills was protective. A sustained high level of IgG antibody to HPV
      16 VLPs was associated with reduced risk for subsequent infection with HPV-16 and
      its genetically related types (i.e., HPV-31, -33, -35, -52, and -58).

PMID- 12198607
TI  - Facilitation of cell adhesion by immobilized dengue viral nonstructural protein 1
      (NS1): arginine-glycine-aspartic acid structural mimicry within the dengue viral
      NS1 antigen.
AB  - Dengue virus infection causes life-threatening hemorrhagic fever. Increasing
      evidence implies that dengue viral nonstructural protein 1 (NS1) exhibits a
      tendency to elicit potentially hazardous autoantibodies, which show a wide
      spectrum of specificity against extracellular matrix and platelet antigens. How
      NS1 elicits autoantibodies remains unclear. To address the hypothesis that NS1
      and matrix proteins may have structural and functional similarity, cell-matrix
      and cell-NS1 interactions were evaluated using a cell-adhesion assay. The present
      study showed that dengue NS1 immobilized on coverslips resulted in more cell
      adhesion than did the control proteins. This cell adhesion was inhibited by
      peptides containing arginine-glycine-aspartic acid (RGD), a motif important for
      integrin-mediated cell adhesion. In addition, anti-NS1 antibodies blocked RGD
      mediated cell adhesion. Although there is no RGD motif in the NS1 protein
      sequence, these data indicate that RGD structural mimicry exists within the NS1
      antigen.

PMID- 12198608
TI  - Genotype mixtures of hepatitis B virus in patients treated with interferon.
AB  - Little is known about coinfection among several hepatitis B virus (HBV)
      genotypes, although previous reports of recombination and genotype shifts
      indicate that this should occur. In the present study, we designed a method to
      identify mixtures of genotype A and another genotype, regardless of whether one
      of them predominates. Using this method, signs of genotypic coinfection were
      found in 20 (67%) of 30 hepatitis B e antigen-positive patients treated with
      interferon (IFN). In 8 of these patients, coinfection or genotype shifts were
      detectable by direct sequencing or standard preS genotyping. In most of these
      cases, genotype changes were detected after a >2-log decrease or increase of the
      HBV DNA level. The presence of genotype mixtures did not significantly influence
      IFN response. Because quasi-species selection may occur at or shortly after
      transmission, patients might acquire HBV infection from subjects who appear to be
      infected with a different genotype. This should be considered when tracing the
      source of HBV infection.

PMID- 12198609
TI  - Analysis and characterization of antiviral drug-resistant cytomegalovirus
      isolates from solid organ transplant recipients.
AB  - The development of cytomegalovirus (CMV) disease and subsequent emergence of drug
      resistant strains was examined in a large group of solid organ transplant
      recipients; drug-resistant CMV was detected in a total of 30 transplant
      recipients (20 lung, 5 kidney, 4 heart, and 1 liver). Drug resistance was
      confirmed both phenotypically and genotypically. The sequences of drug-resistant
      CMV strains from the same patient differed from drug-susceptible baseline
      sequences only at single sites previously confirmed to confer drug resistance. At
      least 1 isolate from each patient had a mutation in the UL97 phosphotransferase
      coding sequence. Mutations in the DNA polymerase gene were found in 6 of 38
      sequenced strains. Lung transplant recipients had the highest incidence of drug
      resistant virus: of the 30 patients, 28 were CMV-seronegative transplant
      recipients of CMV-seropositive organs, which strongly supports the premise that
      drug resistance is most prevalent in that transplant population.

PMID- 12198610
TI  - Association of hypercoagulable states and increased platelet adhesion and
      aggregation with bacterial colonization of intravenous catheters.
AB  - Bacterial adherence to intravenous catheters may be mediated, in part, by
      adherence to coagulation proteins and platelets. The possibility that catheter
      infection is associated with gene polymorphisms that cause hypercoagulability or
      increased platelet stickiness was examined. Among patients with infected
      catheters, there was no increase in the frequency of polymorphisms that increase
      coagulability, including factor V Leiden R506G, factor II (prothrombin) G20210A,
      and methylenetetrahydrofolate reductase C677T, compared with control subjects.
      The incidence of polymorphisms of the platelet beta(3) integrin among patients
      with infected catheters was also similar to that among control subjects. The C/D
      heterozygote of the variable number tandem repeat polymorphism and the C/T
      heterozygote of the KO polymorphism of glycoprotein Ibalpha were more frequent
      among patients with infected catheters than they were among control subjects. In
      a small proportion of patients, a genetic predisposition to platelet stickiness
      may be associated with infection of intravenous catheters, but in the majority, a
      recognized genetic tendency to hypercoagulability or platelet stickiness does not
      underlie infection.

PMID- 12198611
TI  - Characterization of a novel chemotactic factor for neutrophils in the bronchial
      secretions of patients with cystic fibrosis.
AB  - Chronic airway inflammation is a hallmark of cystic fibrosis (CF). Biological
      products with chemotactic activity are essential for neutrophil recruitment to
      sites of inflammation. The presence of a factor with chemotactic activity higher
      than that of interleukin (IL)-8 in the bronchial secretions of patients with CF
      has recently been reported. This article reports that the chemotactic activity of
      this factor remained unaffected by a variety of physical treatments and could be
      distinguished from those of IL-8, formylmethionylleucylphenylalanine, leukotreine
      B4, and platelet-activating factor. The factor induced chemotaxis and
      chemokinesis locomotion of neutrophils, and its chemotactic activity was
      sensitive to pertussis toxin and thapsigargin. Semipurified preparation of the
      chemotactic factor increased transiently intracellular Ca(2+) concentration but
      failed to stimulate the release of neutrophil primary granules and the production
      of superoxide, suggesting that the semipurified chemotactic factor is a Ca(2+)
      dependent chemoattractant of neutrophils, acting via pertussin toxin-sensitive G
      protein-coupled surface receptors, that directs neutrophil movement toward the
      airway epithelium.

PMID- 12198612
TI  - Disease severity in a murine model of lyme borreliosis is associated with the
      genotype of the infecting Borrelia burgdorferi sensu stricto strain.
AB  - The pathogenicity of Borrelia burgdorferi sensu stricto clinical isolates
      representing 2 distinct ribosomal DNA spacer restriction fragment-length
      polymorphism genotypes (RSTs) was assessed in a murine model of Lyme disease. B.
      burgdorferi was recovered from 71.5% and 26.6% of specimens from mice infected
      with RST1 and RST3 isolates, respectively (P<.0001). The average ankle diameter
      and histologic scores for carditis and arthritis were significantly higher after
      2 weeks of infection among mice infected with RST1 isolates than among those
      infected with RST3 isolates (P<.001). These clinical manifestations were
      associated with larger numbers of spirochetes in target tissues but not with the
      serum sensitivity of the individual isolates. Thus, the development and severity
      of disease in genetically identical susceptible hosts is determined mainly by the
      pathogenic properties of the infecting B. burgdorferi isolate. The RST1 genotype
      is genetically homogeneous and thus may represent a recently evolved clonal
      lineage that is highly pathogenic in humans and animals.

PMID- 12198613
TI  - Association between elevated neutrophil defensin levels and endometritis.
AB  - The role of host defenses in the pathogenesis of pelvic inflammatory disease
      (PID) remains largely uncharacterized. The antimicrobial peptides defensins are
      important components of innate host defense. To explore the relationship between
      neutrophil defensins and upper genital tract infection, 377 women who were at
      risk for PID were enrolled in a study. Women infected with Neisseria gonorrhoeae,
      Trichomonas vaginalis, or Chlamydia trachomatis had higher median levels of
      neutrophil defensins (human neutrophil peptides 1-3) in the vagina than did
      uninfected women. Neutrophil defensins were strongly associated with the presence
      of endometritis after the analysis was controlled for the presence of sexually
      transmitted diseases. Vaginal neutrophils were associated with endometritis only
      in the presence of elevated defensin levels, which highlights the importance of
      neutrophil activation, rather than the presence of neutrophils alone, in this
      inflammatory process. Neutrophil defensins appear to participate in the host
      defense in ascending pelvic infection and the pathogenesis of PID.

PMID- 12198614
TI  - Toll-like receptor 2-deficient mice are highly susceptible to Streptococcus
      pneumoniae meningitis because of reduced bacterial clearing and enhanced
      inflammation.
AB  - Toll-like receptor-2 (TLR2) mediates host responses to gram-positive bacterial
      wall components. TLR2 function was investigated in a murine Streptococcus
      pneumoniae meningitis model in wild-type (wt) and TLR2-deficient (TLR2(-/-))
      mice. TLR2(-/-) mice showed earlier time of death than wt mice (P<.02). Plasma
      interleukin-6 levels and bacterial numbers in blood and peripheral organs were
      similar for both strains. With ceftriaxone therapy, none of the wt but 27% of the
      TLR2(-/-) mice died (P<.04). Beyond 3 hours after infection, TLR2(-/-) mice had
      higher bacterial loads in brain than did wt mice, as assessed with luciferase
      tagged S. pneumoniae by means of a Xenogen-CCD (charge-coupled device) camera.
      After 24 h, tumor necrosis factor activity was higher in cerebrospinal fluid of
      TLR2(-/-) than wt mice (P<.05) and was related to increased blood-brain barrier
      permeability (Evans blue staining, P<.02). In conclusion, the lack of TLR2 was
      associated with earlier death from meningitis, which was not due to sepsis but to
      reduced brain bacterial clearing, followed by increased intrathecal inflammation.

PMID- 12198615
TI  - Kinetics of delayed-type hypersensitivity to tuberculin induced by bacille
      Calmette-Guerin vaccination in northern Malawi.
AB  - During 1986-1989, a bacille Calmette-Guerin (BCG) vaccine trial was carried out
      in northern Malawi. The effects of age, sex, and prevaccination delayed-type
      hypersensitivity (DTH) on the time course of the DTH response over 1-36 months
      after vaccination were studied in 2418 persons. DTH response increased rapidly,
      to peak at 31-90 days after vaccination, when most persons had a measurable
      response. This was followed by a marked decline by 181-365 days, particularly in
      those <15 years old at vaccination, followed by a more gradual decline.
      Prevaccination DTH was the single best predictor of postvaccination DTH. BCG
      induced DTH responsiveness appears to decline more rapidly in tropical than in
      temperate environments. This may reflect high prevalence of exposure to other
      infections, which induce a Th2 bias or compete for "space" within the T
      lymphocyte compartment. The inability of some persons to mount a persistent DTH
      response probably reflects genetic background and/or environmental exposure
      history.

PMID- 12198616
TI  - Functional properties of the T cell receptor repertoire in responding to the
      protective domain of heat-shock protein 60 from Histoplasma capsulatum.
AB  - Cells expressing the T cell receptor beta-chain variable region (Vbeta) 6
      constitute the majority of T cells responding to the protective domain (F3) of
      heat-shock protein 60 from Histoplasma capsulatum. This subset of cells exhibits
      a T helper type 1 (Th1) profile and is pivotal in protection. In this study,
      additional F3-reactive T cell lines were generated, leading to the discovery of a
      Th2 line. Vbeta usage by clones was more diverse than has been previously
      recognized. Nearly all Th2 clones expressed Vbeta8.1/8.2, whereas Th1 clones
      expressed Vbeta11 or Vbeta6. In adoptive transfer studies, only the Vbeta6(+) Th1
      clone prolonged survival; all Th2 clones accelerated mortality. The ameliorative
      effect of the Vbeta6(+) Th1 clone was abrogated by treatment with monoclonal
      antibody to interferon-gamma. Neutralization of interleukin-4 reversed the
      shortened survival of mice to which the Vbeta6(+) Th2 clone was administered.
      Thus, F3-mediated protection is confined to a defined Vbeta population, but
      exacerbation of disease is mediated by multiple Vbeta families.

PMID- 12198617
TI  - Experimental chemotherapy against Trypanosoma cruzi infection: essential role of
      endogenous interferon-gamma in mediating parasitologic cure.
AB  - Studies in humans and in experimental models suggest the involvement of the
      immune system for efficacy of drug treatment against protozoan parasites. This
      study tested this hypothesis by using various cytokine and inducible nitric oxide
      synthase (iNOS) knockout (KO) mice infected with Trypanosoma cruzi and treated
      with benznidazole. In contrast with the 100% parasitologic cure rate achieved in
      wild-type animals, benznidazole failed to cure 100%, 42%, 35%, and 28% of
      interferon-gamma, interleukin-12 (protein 40), protein 55-tumor necrosis factor
      receptor, and iNOS KO mice, respectively. These results suggest that activation
      of the immune system by the parasite and endogenous interferon-gamma play a major
      role in the efficacy of benznidazole against infection with T. cruzi.

PMID- 12198618
TI  - Cytomegalovirus (CMV) virus load kinetics to predict recurrent disease in solid
      organ transplant patients with CMV disease.
AB  - Despite standard therapy, cytomegalovirus (CMV) disease recurs in a significant
      proportion of organ transplant recipients. The kinetics of CMV load in response
      to therapy may allow early prediction of recurrence. CMV loads were obtained at
      regular intervals after starting ganciclovir therapy in 52 transplant recipients
      with CMV disease. Virus load kinetics were analyzed using decay curves to assess
      viral dynamics, including half-life and time to viral clearance. Recurrent CMV
      disease occurred in 12 (23%) of 50 patients. The time period to viral clearance
      was longer among patients with recurrence of CMV disease (P=.002), and lack of
      clearance was also associated among patients with disease recurrence (P<.001).
      Viral kinetics followed a logarithmic decay curve expressed by the equation
      y=y(0)e(-ax). Virus load half-life was 8.8 days among patients with recurrence
      versus 3.17 days among patients without recurrence (P=.001). This was not
      explainable by detectable ganciclovir resistance. CMV load kinetics are useful
      for identifying, at a very early stage, patients who are more likely to have
      recurrence.

PMID- 12198619
TI  - Immune-globulin prophylaxis of respiratory syncytial virus infection in patients
      undergoing stem-cell transplantation.
AB  - Thirty-two patients undergoing allogeneic hematopoietic stem-cell transplantation
      were given respiratory syncytial virus (RSV) immune globulin (RSVIG) at the time
      of transplantation and again 3 weeks later. Antibody titers to RSV, human
      parainfluenza virus 3, measles, and influenza H1N1, H3N2, and B were measured
      prior to administration of RSVIG and 6 more times over the course of the
      subsequent 6 weeks. Baseline antiviral titers and increases in antibody after
      administration of RSVIG were extremely variable for all the viruses. In 18
      patients in whom the baseline titers of antibody titers to RSV-F protein were
      1:640-1:2048, there was a 7.7-fold initial increase in these titers after the
      first dose of RSVIG, compared with a 2.1-fold increase in 14 patients with
      baseline titers of 1:4096-1:20,840; increases in titers of antibody against the
      other viruses after the first dose of RSVIG reflected similar variability. The
      subset of patients with the lowest titers appear to receive the greatest benefit
      from administration of RSVIG.

PMID- 12198620
TI  - Correlation between respiratory syncytial virus genotype and severity of illness.
AB  - Respiratory syncytial virus (RSV) causes seasonal outbreaks of respiratory tract
      infections, but the viral factors associated with virulence remain unknown. To
      determine whether RSV genotype correlated with severity of illness, isolates were
      characterized by phylogenetic analysis of the RSV G gene, and a composite score
      was used to quantify severity of illness. During the 1998-1999 and 1999-2000
      winter seasons, 137 subgroup A and 84 subgroup B isolates were identified. The
      severity of illness caused by subgroup A isolates did not differ from that caused
      by subgroup B isolates (P=.086). However, the GA3 clade was associated with
      significantly greater severity of illness, compared with clades GA2 (P=.004) and
      GA4 (P=.016). In a subpopulation of patients < or =24 months old who had no known
      risk factors for severe RSV disease, clade GA3 was again associated with greater
      severity of illness, compared with clade GA2 (P=.018). Severity of RSV infection
      is associated with RSV genotype.

PMID- 12198621
TI  - Human leukocyte antigen-B8-DR3 is a more important risk factor for severe Puumala
      hantavirus infection than the tumor necrosis factor-alpha(-308) G/A polymorphism.
AB  - The tumor necrosis factor (TNF)-alpha(-308) G/A polymorphism (TNF-2) is in
      linkage disequilibrium with the human leukocyte antigen (HLA)-B8-DR3 haplotype.
      Both factors have been associated with severe Puumala hantavirus-induced
      nephropathia epidemica (NE). To examine which part of this extended haplotype
      might show the strongest association with the outcome of NE, the HLA-B, HLA-DRB1,
      and TNF-alpha(-308) alleles in 116 hospital-treated patients with NE were
      analyzed. The findings pointing to clinically severe NE were strongly associated
      with HLA-B8-DR3 haplotype. There was a trend toward severe disease in persons
      positive for TNF-2. This was probably due to strong linkage disequilibrium with
      HLA-B8-DR3, since there were no differences in the clinical severity of NE when
      TNF-2-positive/B8-DR3-negative persons were compared with TNF-2-negative/B8-DR3
      negative persons. It is concluded that the HLA-B8-DR3 haplotype is an important
      contributor to the course of NE. The data indicate that the TNF-2 allele is not
      an independent risk factor for severe NE but a passive component in the extended
      haplotype.

PMID- 12198622
TI  - Acute human immunodeficiency virus replication causes a rapid and persistent
      impairment of Vgamma9Vdelta2 T cells in chronically infected patients undergoing
      structured treatment interruption.
AB  - T cells expressing Vgamma9Vdelta2 display lytic and proliferative responses
      against human immunodeficiency virus (HIV)-infected cells and release antiviral
      soluble factors. Chronic HIV-positive patients have deep changes in the
      composition and function of the circulating gammadelta T cell pool that are
      restored by highly active antiretroviral therapy (HAART). gammadelta T cells were
      analyzed during the rapid plasma HIV RNA rebound in HIV-infected patients
      undergoing structured treatment interruption (STI). A loss in circulating
      Vgamma9Vdelta2 T cells was observed, indicating that acute HIV replication may
      influence Vgamma9Vdelta2 homeostasis. These cells were lost among CD45RA(-)CD27(
      ) Vgamma9Vdelta2 T cell effectors, and a significant unresponsiveness, measured
      as antigen-driven interferon-gamma production, was observed during STI. After
      HAART resumption and consequent inhibition of HIV replication, Vgamma9Vdelta2 T
      cell reactivity was restored both quantitatively and functionally. These
      observations indicate that Vgamma9Vdelta2 T cells are activated early after
      active HIV replication but are rapidly lost when viremia is not controlled.

PMID- 12198623
TI  - Effect of prolonged discontinuation of successful antiretroviral therapy on CD4+
      T cell decline in human immunodeficiency virus-infected patients: implications
      for intermittent therapeutic strategies.
AB  - This study evaluates the change in CD4(+) T cell counts among patients who
      achieved complete viral suppression and subsequently discontinued highly active
      antiretroviral therapy (HAART). We included 72 human immunodeficiency virus (HIV)
      1-infected patients with plasma HIV RNA loads of <500 copies/mL for at least 3
      months who then discontinued therapy for at least 12 weeks. The median CD4(+) T
      decay while off HAART was 16 cells/mm(3)/month (interquartile range, -6 to -34
      cells/month). The mean follow-up after therapy ended was 45 weeks. The slope of
      the CD4(+) T cell decay was inversely correlated with the increase of CD4(+) T
      cells while receiving HAART, baseline virus load, CD4(+) T cell count at the time
      therapy was discontinued, age, and duration HIV RNA levels were undetectable. In
      a multiple regression analysis model, the increase of CD4(+) T cells while
      receiving therapy and age were independently associated with the rate of CD4(+) T
      cell loss.

PMID- 12198624
TI  - Seroepidemiologic studies of serotype VIII group B Streptococcus in Japan.
AB  - Levels of antibody to serotype VIII group B Streptococcus (GBS) were surveyed in
      serum samples from 583 pregnant women, from 461 neonates born to these women, and
      from 4 mother-and-neonate pairs with early-onset serotype VIII sepsis.
      Colonization by serotype VIII GBS was associated with significantly higher serum
      concentrations of serotype-specific antibodies (geometric mean [GM], 5.53 micro
      g/mL), compared with both noncolonization (1.53 micro g/mL) and colonization with
      other serotypes (2.19 micro g/mL). There was excellent correlation between
      antibody levels in mothers and those in their neonates. The prevalence of
      positive antibody levels, when arbitrarily defined, according to antibody levels
      in neonatal sepsis (GM, 0.49 micro g/mL) as >1.0 micro g/mL, was 58% of all
      pregnant women and 85% of the women colonized by serotype VIII. This high
      serotype prevalence may explain, at least in part, why serotype VIII causes early
      onset neonatal disease at rates lower than those which would be expected on the
      basis of its prevalence in mothers in Japan who are colonized by GBS.

PMID- 12198626
TI  - Coccidioidomycosis outbreak among United States Navy SEALs training in a
      Coccidioides immitis-endemic area--Coalinga, California.
AB  - An outbreak of coccidioidomycosis among 22 Navy SEALs occurred during training
      exercises in Coalinga, California. Ten (45%) of the 22 men had serologic evidence
      of acute coccidioidomycosis, the highest attack rate ever reported for a military
      unit. All case patients were symptomatic, and 50% had abnormal chest radiographs.
      There were no cases of dissemination and no deaths to date. Coccidioidomycosis
      continues to be a threat to military members and civilians who reside or train in
      areas where Coccidioides immitis, the causative agent, is endemic.

PMID- 12198625
TI  - Uropathogenic Escherichia coli as agents of diverse non-urinary tract
      extraintestinal infections.
AB  - Escherichia coli isolates from 3 consecutively encountered patients with serious,
      invasive, non-urinary tract extraintestinal infections (pneumonia, deep surgical
      wound infection, and vertebral osteomyelitis with associated
      epidural/psoas/iliacus abscesses) were characterized, using molecular methods, as
      to extended virulence genotype and phylogenetic background. All 3 isolates
      exhibited virulence genotypes and genomic profiles characteristic of specific
      familiar virulent clones of extraintestinal pathogenic E. coli (ExPEC), which
      traditionally have been regarded primarily as uropathogenic or as associated with
      meningitis. These included E. coli O1/O2:K1:H7, E. coli O18:K1:H7, and a recently
      described E. coli O11/O17/O77:K52:H18 clonal group (clonal group A). These
      findings demonstrate the extraintestinal pathogenic versatility of ExPEC clones,
      which supports the use of an inclusive designation for such strains and suggests
      the possibility of cross-syndrome protective interventions. They also provide
      novel evidence that multidrug-resistant epidemic clonal group A can cause
      extraintestinal infections other than uncomplicated urinary tract infections and
      can cause them in hosts other than young women.

PMID- 12198627
TI  - Vaccination of corticosteroid immunosuppressed mice against invasive pulmonary
      aspergillosis.
AB  - Invasive pulmonary aspergillosis is an emerging devastating infection in the
      immunocompromised host that is treated with corticosteroids for neoplastic
      disease or for organ transplantation. By use of a model of invasive pulmonary
      aspergillosis in corticosteroid-treated CF-1 mice, prior infection and 2
      Aspergillus fumigatus vaccine preparations (sonicate and filtrate) administered
      intranasally and subcutaneously were tested for efficacy in protecting against
      subsequent lethal A. fumigatus infection. The mortality rates were as follows:
      control subjects, 100%; prior infection, 12.5%; sonicate administered
      intranasally, 29%; sonicate given subcutaneously, 0%; filtrate given
      intranasally, 75%; and filtrate given subcutaneously, 50%. Prior infection and A.
      fumigatus sonicate vaccine administered by 2 routes protected corticosteroid
      treated animals against subsequent lethal invasive pulmonary aspergillosis. The
      sonicate vaccine was more protective, but the subcutaneous route was more
      effective.

PMID- 12198628
TI  - Trypanosoma cruzi parasitemia in chronic Chagas disease: comparison between human
      immunodeficiency virus (HIV)-positive and HIV-negative patients.
AB  - This study evaluated Trypanosoma cruzi parasitemia in persons with chronic Chagas
      disease, compared the parasitemia in human immunodeficiency virus (HIV)-positive
      and -negative subjects, and, for HIV-positive subjects, analyzed the association
      between parasitemia and occurrence of acquired immunodeficiency syndrome-defining
      illnesses, CD4 cell counts, HIV loads, and antiretroviral therapy. In total, 110
      adults with chronic Chagas disease (29 HIV positive, 81 HIV negative) were
      studied. T. cruzi parasitemia was evaluated by xenodiagnosis, blood culture, and
      direct microscopic examination of blood. T. cruzi parasitemia was detected
      significantly more frequently in HIV-positive than in HIV-negative subjects (odds
      ratio, 12.3; 95% confidence interval, 3.7-41.2). HIV-positive patients also had
      higher levels of parasitemia. No statistically significant association was seen
      between parasitemia and the variables of interest among the HIV-positive
      subjects.

PMID- 12198629
TI  - Evidence of endogenous reactivation of tuberculosis after a long period of
      latency.

PMID- 12198630
TI  - Recurrent urinary tract infections: relapses or reinfections?

PMID- 12198631
TI  - Editorial: the coming revolution in the treatment of prostate cancer patients.

PMID- 12198632
TI  - Hormonal therapy of prostate cancer.
AB  - In the 60 years since Huggins first demonstrated the hormone dependency of
      prostate cancer, the introduction of various means of hormonal manipulation has
      resulted in modest achievements. Orchiectomy reduced testosterone but was
      irreversible and associated with reduced quality of life. Diethylstilbestrol
      (DES) represented the first alternative to surgical castration. However,
      cardiovascular adverse events severely limited its use. The luteinizing hormone
      releasing hormone (LHRH) agonists offered true medical castration but suffered
      from problems of testosterone surge and tumor flare. The introduction of
      antiandrogens in combination with LHRH agonists appears on meta-analysis not to
      have improved survival and has implications for the cost and convenience of
      therapy, as well as added toxicity. Gonadotropin-releasing hormone (GnRH)
      antagonists offer for the first time a truly rapid medical means of reducing
      testosterone and also suppress follicle-stimulating hormone (FSH). However, the
      clinical benefit of this new class of drugs remains to be evaluated.

PMID- 12198634
TI  - Therapeutic considerations for patients with high-risk, nonmetastatic, prostate
      cancer.
AB  - The management of patients with high-risk, early-stage, prostate cancer
      represents a major challenge to all disciplines involved in the treatment of this
      common malignant neoplasm. Definition of the natural history of this disease,
      including the identification of key prognostic factors, in addition to the
      availability of active systemic therapeutic modalities for patients with advanced
      disease, are among the basic requirements that allow for early intervention in
      high-risk patients. Emerging new antiprogression approaches, targeted at various
      known stages of the metastatic cascade with the potential benefit of altering the
      natural history of early prostate cancer are attractive alternatives for early
      interventions with innovative programs. Studies on the natural history of
      patients with evidence of biochemical relapse following local treatment provide
      the basis for appropriate estimation of the risk ratio for development of
      clinical metastasis and selection of candidates for aggressive implementation of
      early treatment. The study of new candidate biomarkers of disease activity should
      be included in the context of clinical trials. Genotypic and phenotypic
      characterization of patients in clinical trials may enhance future therapeutic
      prospects in this disease.

PMID- 12198633
TI  - Neoadjuvant strategies for prostate cancer prior to radical prostatectomy.
AB  - Although definitive therapy with either radical prostatectomy or radiation
      therapy can be effective, the optimal treatment for prostatic adenocarcinoma
      remains controversial. Patients may be at significant risk for primary treatment
      failure even with apparent clinically localized disease. Thus, there has been
      increased interest in initial multimodal therapy in order to maximize the
      potential for cure. Neoadjuvant hormonal therapy prior to radical prostatectomy
      has been used for several decades and a large body of literature discusses its
      use; nevertheless, the current data suggest that it only decreases rates of
      positive surgical margins without improving prostate-specific antigen (PSA)-free
      or disease-free survival. Novel neoadjuvant hormonal and chemotherapeutic
      regimens are under investigation and may improve outcomes for patients undergoing
      radical prostatectomy.

PMID- 12198635
TI  - Secondary hormonal manipulation of prostate cancer.
AB  - Prostate cancer is the second leading cause of cancer mortality among men in
      Western countries. The initial treatment of advanced prostate cancer is
      suppression of testicular androgen production by medical or surgical castration,
      but nearly all men with metastases will develop disease progression. Patients
      with hormone-resistant prostate cancer (HRPC) have a median survival of
      approximately 18 months, and no therapy has yet demonstrated a definitive
      survival advantage. However, in the past several years, a number of promising new
      treatment strategies have emerged. One of the most important new treatment
      strategies involves secondary hormonal manipulation after the failure of primary
      androgen deprivation. This approach is predicated on the recognition that HRPC is
      a heterogeneous disease, and some patients may respond to alternative hormonal
      interventions despite the presence of castrate levels of testosterone.

PMID- 12198636
TI  - Chemotherapy for androgen-independent prostate cancer.
AB  - While men with metastatic prostate cancer frequently show a good initial response
      to androgen ablation, few options have been available for progressive hormone
      refractory prostate cancer, and survival following chemotherapy has not exceeded
      9 to 12 months. The combination of prednisone and mitoxantrone has significant
      palliative effects on bone pain but does not extend survival. The combination of
      estramustine phosphate (EMP) with the taxanes paclitaxel or docetaxel produces
      greater than additive cytotoxicity in vivo, and phase I and II studies of taxane
      based therapy demonstrate improved survival in hormone-refractory prostate cancer
      compared to historical controls. Docetaxel appears to have relatively high
      activity as a single agent and in combination with EMP. Further studies are
      needed to clarify the optimum dose of EMP, taking into account potential
      cardiovascular toxicity. Phase III studies of its combination with docetaxel are
      in progress.

PMID- 12198637
TI  - What is the role of nondrug methods in the nursing care of patients with acute
      pain?

PMID- 12198638
TI  - Pain problems in young adults and pain reduction strategies.
AB  - The purpose of this study was to survey young adults about their pain and pain
      treatments to identify ways to decrease risk for chronic pain. The sample
      consisted of 89 young adults between the ages of 18 and 25 who had experienced
      some pain during the past month and who did not have a chronic condition commonly
      associated with a pain problem. Community dwelling young adults were screened for
      eligibility and administered the Brief Pain Inventory Short Form (BPI-SF) during
      a face-to-face interview. They were asked to describe the intensity of their pain
      during the past month using the 0 to 10 numeric scales from the BPI-SF. A pilot
      study supported these methods. Participants reported their worst pain as M = 6.5
      (SD = 1.71), their average pain as M = 4.1 (SD = 1.85), and their least pain
      intensity as M = 1.8 (SD = 1.68). They reported 20 different self-treatments for
      their pain. Although 56.2% used nonopioid analgesics, 22.5% used no pain
      treatments. Participants reported 61.3% pain relief from self-treatments. Young
      women used analgesics more often than young men (64.9% and 40.6%, respectively,
      Chi;(2) [1] = 4.91, p <.03). Pain moderately interfered with their mood (M = 4.1;
      SD = 3.00) and general lives (M = 3.9; SD = 2.42). Identifying young adults at
      risk for chronic pain provides the first step in educating them about effective
      ways to prevent chronic pain. Results from this study provide some initial
      groundwork for educational interventions to prevent chronic pain in young adults.

PMID- 12198639
TI  - The effects of a pain management education program on the knowledge level and
      attitudes of clinical staff.
AB  - Two of the most important variables in effective pain management are the
      knowledge level and attitudes of the clinical staff at the bedside. Gaps in
      knowledge or uninformed attitudes can prevent optimal pain management. A baseline
      survey of staff knowledge and attitudes can guide educational and other process
      improvement efforts. Improvements can then be quantified. A multidisciplinary and
      multifaceted approach to pain management can improve the knowledge and attitudes
      of bedside clinicians.

PMID- 12198640
TI  - From chronic pain patient to peer: benefits and risks of volunteering.
AB  - Peer volunteers have been used as cost-effective adjuncts to professional
      services in other settings and populations, but not a heterogeneous sample of
      patients with chronic pain. This study evaluated the transition from "patient" to
      "peer," identifying possible benefits or harm associated with volunteering. Peers
      provided descriptive data and questionnaires, including measures of pain,
      disability, self-efficacy, and depression before and after three periods: as a
      patient, during training, and while volunteering. Average pain intensity scores
      declined while participants were patients (7.1 to 4.2), rose slightly (5.8)
      before training, and dropped again after training and volunteering (4.3 and 3.6,
      respectively). A similar pattern was noted for disability. Depression scores
      continued to decline after initially dropping, and self-efficacy scores remained
      stable after the initial 40% rise as a patient. Two themes, "making a connection"
      and "a sense of purpose," emerged from the narrative data. Descriptive data
      provided further support that volunteering benefited both patients and peers.
      This study supports the viability of using peer volunteers for clinical or
      research endeavors. Improvements in pain, disability, and depression were
      reported immediately after training and after volunteering for several months
      without evidence of harm. Despite encountering challenges, the rewards of this
      altruistic endeavor outweighed any frustrations experienced by volunteers with
      chronic pain.

PMID- 12198641
TI  - The pain experience of adolescents after acute blunt traumatic injury.
AB  - Because little is known about adolescent pain, in particular pain after blunt
      traumatic injury, a descriptive exploratory approach was used to examine the pain
      experience of adolescents after acute blunt traumatic injury in three contexts:
      at the scene of the accident, in the emergency department, and in the hospital
      setting. For the 13 adolescents (11-17 years) who experienced multiple sites of
      blunt unintentional injury, the majority recalled their worst pain at the scene
      and in the emergency department, with high, intense pain persisting into the
      hospital setting. Regardless of the context, adolescents recalled multiple
      aspects of their pain experience. Study findings have implications for the
      understanding and management of adolescent pain resulting from blunt traumatic
      injury.

PMID- 12198643
TI  - Ursodeoxycholic acid in cholestatic liver disease: mechanisms of action and
      therapeutic use revisited.
AB  - Ursodeoxycholic acid (UCDA) is increasingly used for the treatment of cholestatic
      liver diseases. Experimental evidence suggests three major mechanisms of action:
      (1) protection of cholangiocytes against cytotoxicity of hydrophobic bile acids,
      resulting from modulation of the composition of mixed phospholipid-rich micelles,
      reduction of bile acid cytotoxicity of bile and, possibly, decrease of the
      concentration of hydrophobic bile acids in the cholangiocytes; (2) stimulation of
      hepatobiliary secretion, putatively via Ca(2+)- and protein kinase C-alpha
      dependent mechanisms and/or activation of p38(MAPK) and extracellular signal
      regulated kinases (Erk) resulting in insertion of transporter molecules (e.g.,
      bile salt export pump, BSEP, and conjugate export pump, MRP2) into the
      canalicular membrane of the hepatocyte and, possibly, activation of inserted
      carriers; (3) protection of hepatocytes against bile acid-induced apoptosis,
      involving inhibition of mitochondrial membrane permeability transition (MMPT),
      and possibly, stimulation of a survival pathway. In primary biliary cirrhosis,
      UDCA (13-15 mg/kg/d) improves serum liver chemistries, may delay disease
      progression to severe fibrosis or cirrhosis, and may prolong transplant-free
      survival. In primary sclerosing cholangitis, UDCA (13-20 mg/kg/d) improves serum
      liver chemistries and surrogate markers of prognosis, but effects on disease
      progression must be further evaluated. Anticholestatic effects of UDCA have also
      been reported in intrahepatic cholestasis of pregnancy, liver disease of cystic
      fibrosis, progressive familial intrahepatic cholestasis, and chronic graft-versus
      host disease. Future efforts will focus on definition of additional clinical uses
      of UDCA, on optimized dosage regimens, as well as on further elucidation of
      mechanisms of action of UDCA at the molecular level.

PMID- 12198644
TI  - Virahep-C.

PMID- 12198645
TI  - Differentiated properties of hepatocytes induced from pancreatic cells.
AB  - Transdifferentiation of pancreas to liver is a well-recognized phenomenon and has
      been described in animal experiments and human pathology. We recently produced an
      in vitro model for the transdifferentiation (or conversion) of the pancreatic
      cell line AR42J-B13 to hepatocytes based on culture with dexamethasone (Dex). To
      determine whether the hepatocytes express markers of hepatic intermediary
      metabolism and detoxification, we investigated the patterns of expression of
      glucokinase, cytochrome P450s CYP3A1 and CYP2B1/2, testosterone/4-nitrophenol
      uridine diphosphate glucuronosyltransferase (UDPGT), and aryl sulfotransferase.
      All were expressed. We also determined the expression of 2 enzymes involved in
      ammonia detoxification: carbamoylphosphate synthetase I (CPS I) and glutamine
      synthetase (GS). These enzymes are normally strictly compartmentalized in liver
      in a wide periportal pattern and the last downstream perivenous hepatocytes,
      respectively. Following culture with Dex, CPS I and GS are expressed in 2
      different cell populations, suggesting that both periportal and perivenous
      hepatocytes are induced. We also produced a reporter assay based on the
      activation of green fluorescent protein (GFP) by the transthyretin (TTR) promoter
      or glucose-6-phosphatase (G6Pase) promoter. After culture with Dex, transfected
      cells begin to express GFP, showing that hepatic promoters are activated in
      concert with the induction of the hepatocyte phenotype. Lastly, we examined the
      stability of the hepatic phenotype and found that some cells still express liver
      markers (transferrin or albumin) up to 14 days after removal of Dex. In
      conclusion, these results suggest that pancreatic hepatocytes produced by this
      method may offer an alternative model to primary cultures of hepatocytes for the
      study of liver function.

PMID- 12198646
TI  - Delayed liver regeneration in peroxisome proliferator-activated receptor-alpha
      null mice.
AB  - Peroxisome proliferator chemicals, acting via the peroxisome proliferator
      activated receptor-alpha (Pparalpha), are potent hepatic mitogens and carcinogens
      in mice and rats. To test whether Pparalpha is required for hepatic growth in
      response to other stimuli, we studied liver regeneration and hepatic gene
      expression following partial hepatectomy (PH) of wild-type and Pparalpha-null
      mice. Pparalpha-null mice had a 12- to 24-hour delay in liver regeneration
      associated with a delayed onset and lower peak magnitude of hepatocellular DNA
      synthesis. Furthermore, these mice had a 24-hour lag in the hepatic expression of
      the G(1)/S checkpoint regulator genes Ccnd1 and cMyc and increased expression of
      the IL-1beta cytokine gene. Hepatic expression of Ccnd1, cMyc, IL-1r1, and IL-6r
      was induced in wild-type mice, but not Pparalpha-null mice, after acute exposure
      to the potent Pparalpha agonist Wy-14,643, indicating a role for Pparalpha in
      regulating the expression of these genes. Expression of the fatty acid omega
      hydroxylase gene Cyp4a14, a commonly used indicator gene for Pparalpha
      activation, was strongly induced in wild-type mice after hepatectomy, suggesting
      that altered hepatocyte lipid processing may also contribute to the impaired
      regeneration in mice lacking the Pparalpha gene. In conclusion, liver
      regeneration in Pparalpha-null mice is transiently impaired and is associated
      with altered expression of genes involved in cell cycle control, cytokine
      signaling, and fat metabolism.

PMID- 12198647
TI  - Pretreatment with FK506 up-regulates insulin receptors in regenerating rat liver.
AB  - This report examines the effect of FK506 pretreatment on liver insulin receptor
      expression in partially (70%) hepatectomized rats. FK506 pretreatment led to an
      increased insulin receptor number 24 hours after hepatectomy, detected by means
      of insulin binding and cross-linking procedures. This increase was related to
      enhanced insulin receptor expression determined by in vitro mRNA translation and
      Western blot techniques. We also tested the functionality of the expressed
      insulin receptors by [(3)H] thymidine incorporation into DNA in insulin
      stimulated hepatocytes. The results show that FK506 pretreatment elicits an
      increase in the amount of insulin receptor alpha-subunits as measured by Western
      blot. Maximum alpha-subunit expression recorded 24 hours after surgery was
      preceded by increased insulin receptor mRNA levels, which were detected 6 hours
      after hepatectomy. Moreover, in FK506-pretreated rat hepatocytes, obtained from
      remnant livers 24 hours after partial hepatectomy (PH), the increase in insulin
      receptor number was associated with improved sensitivity to the hormone. However,
      in both experimental groups (FK506-pretreated and nonpretreated rats), the
      sensitivity of hepatocytes toward epidermal growth factor (EGF) showed no
      significant change, which suggests a specific effect of FK506 on insulin receptor
      expression. In conclusion, our findings suggest that FK506 pretreatment induces
      insulin receptor expression in regenerating rat liver and promotes liver
      regeneration in hepatectomized rats.

PMID- 12198648
TI  - Preconditioning protects liver and lung damage in rat liver transplantation: role
      of xanthine/xanthine oxidase.
AB  - This study was designed to evaluate whether ischemic preconditioning could confer
      protection against liver and lung damage associated with liver transplantation.
      The effect of preconditioning on the xanthine/xanthine oxidase (XOD) system in
      liver grafts subjected to 8 and 16 hours of cold ischemia was also evaluated.
      Increased xanthine levels and marked conversion of xanthine dehydrogenase (XDH)
      to XOD were observed after hepatic cold ischemia. Xanthine/XOD could play a role
      in the liver and lung damage associated with liver transplantation. This
      assumption is based on the observation that inhibition of XOD reduced
      postischemic reactive oxygen species (ROS) generation and hepatic injury as well
      as ensuing lung inflammatory damage, including neutrophil accumulation, oxidative
      stress, and edema formation. Ischemic preconditioning reduced xanthine
      accumulation and conversion of XDH to XOD in liver grafts during cold ischemia.
      This could diminish liver and lung damage following liver transplantation. In the
      liver, preconditioning prevented postischemic ROS generation and hepatic injury
      as well as the injurious effects in the lung following liver transplantation.
      Administration of xanthine and XOD to preconditioned rats led to hepatic ROS and
      transaminase levels similar to those found after reperfusion and abolished the
      protective effect of preconditioning on the lung inflammatory damage. In
      conclusion, ischemic preconditioning reduces both liver and lung damage following
      liver transplantation. This endogenous protective mechanism is capable of
      blocking xanthine/XOD generation in liver grafts during cold ischemia.

PMID- 12198649
TI  - Blockade of the L-arginine/NO synthase pathway worsens hepatic apoptosis and
      liver transplant preservation injury.
AB  - Organ graft preservation injury is a major problem complicating liver
      transplantation. The L-arginine/nitric oxide pathway has protective effects in
      several models of liver injury. The purpose of this study was to evaluate the
      role of the L-arginine/NO synthase (NOS) pathway on liver preservation injury and
      to characterize endogenous inducible NOS (iNOS) expression. Orthotopic liver
      transplantation was performed with 18-hour University of Wisconsin preservation
      solution in syngeneic rats. Recipient rats were either untreated or treated with
      L-arginine, D-arginine, nonspecific NOS inhibitor N(G)-nitro-L-arginine methyl
      ester (L-NAME), or iNOS selective inhibitor L-N(6)-(1-imino-ethyl)lysine (L-NIL)
      after revascularization. As early as 1 hour following reperfusion, circulating
      arginine levels decreased 10-fold and ornithine levels increased 4-fold. A
      corresponding increase in arginase I protein was detected in serum. To address
      the profound arginine deficiency, we supplemented recipients with arginine after
      transplantation. L-arginine (but not D-arginine) supplementation significantly
      reduced preservation injury 12 hours after reperfusion, suggesting that the
      protective effect of L-arginine was mediated through the generation of NO. iNOS
      protein expression peaked in the liver 6 to 12 hours following reperfusion.
      Blockade of the L-arginine/NO pathway with L-NAME significantly increased
      necrotic and apoptotic cell death in the transplanted graft. Addition of the iNOS
      selective inhibitor L-NIL mildly increased liver transaminase levels and also
      increased apoptosis in the liver graft. In conclusion, transplant recipients are
      profoundly arginine deficient postreperfusion due to arginase release. L-Arginine
      supplementation and NO synthesis decrease necrotic and apoptotic cell death and
      ameliorate liver transplant preservation injury.

PMID- 12198650
TI  - Cell adhesion regulates platelet-derived growth factor-induced MAP kinase and PI
      3 kinase activation in stellate cells.
AB  - The biologic effects of growth factors are dependent on cell adhesion, and a
      cross talk occurs between growth factors and adhesion complexes. The aim of the
      present study was to evaluate the influence of cell adhesion on the major
      intracellular signaling pathways elicited by platelet-derived growth factor
      (PDGF) in hepatic stellate cells (HSC). PDGF signaling was investigated in an
      experimental condition characterized by lack of cell adhesion for different
      intervals of time. Basal and PDGF-induced focal adhesion kinase (FAK) tyrosine
      phosphorylation was maintained in a condition of cell suspension for 2, 4, and 6
      hours, whereas it was completely lost after 12 and 24 hours. We examined MAP
      kinase activity at 2 and 24 hours, corresponding to the higher and lower levels
      of FAK phosphorylation. In these experiments, MAP kinase activity correlated with
      FAK phosphorylation. Stimulation with PDGF was able to cause Ras-GTP loading only
      in adherent cells. The ability of PDGF to induce phosphatidylinositol 3-kinase
      (PI 3-K) activity was abrogated in cells maintained in suspension. The Ser473
      phosphorylation of Akt was only marginally affected by the lack of cell adhesion.
      We then evaluated the association of FAK with c-Src. This association was found
      to be cell adhesion dependent, and it did not appear to be dependent from
      phosphorylated FAK. These changes in PDGF-induced intracellular signaling were
      associated with a remarkable reduction of PDGF-proliferative potential in
      nonadherent cells, although no marked differences in the apoptotic rate were
      observed. In conclusion, these results suggest that cell adhesion differentially
      regulates major signaling pathways activated by PDGF in HSC.

PMID- 12198651
TI  - Effect of tauroursodeoxycholic acid on endoplasmic reticulum stress-induced
      caspase-12 activation.
AB  - Activation of death receptors and mitochondrial damage are well-described common
      apoptotic pathways. Recently, a novel pathway via endoplasmic reticulum (ER)
      stress has been reported. We assessed the role of tauroursodeoxycholic acid
      (TUDCA) in inhibition of caspase-12 activation and its effect on calcium
      homeostasis in an ER stress-induced model of apoptosis. The human liver-derived
      cell line, Huh7, was treated with thapsigargin (TG) to induce ER stress. Typical
      morphologic changes of ER stress preceded development of apoptotic changes,
      including DNA fragmentation and cleavage of poly (adenosine diphosphate-ribose)
      polymerase (PARP), as well as activation of caspase-3 and -7. Elevation of
      intracellular calcium levels without loss of mitochondrial membrane potential
      (MMP) was shown using Fluo-3/Fura-red labeling and flow cytometry, and confirmed
      by induction of Bip/GRP78, a calcium-dependent chaperon of ER lumen. These
      changes were accompanied by procaspase-12 processing. TUDCA abolished TG-induced
      markers of ER stress; reduced calcium efflux, induction of Bip/GRP78, and caspase
      12 activation; and subsequently inhibited activation of effector caspases and
      apoptosis. In conclusion, we propose that mitochondria play a secondary role in
      ER-mediated apoptosis and that TUDCA prevents apoptosis by blocking a calcium
      mediated apoptotic pathway as well as caspase-12 activation. This novel mechanism
      of TUDCA action suggests new intervention methods for ER stress-induced liver
      disease.

PMID- 12198652
TI  - Hyperosmolarity triggers CD95 membrane trafficking and sensitizes rat hepatocytes
      toward CD95L-induced apoptosis.
AB  - The effect of hyperosmolarity on CD95 membrane targeting and CD95 ligand (CD95L)
      induced apoptosis was studied in rat hepatocytes. CD95 showed a predominant
      intracellular localization in normoosmotically exposed rat hepatocytes, whereas
      hyperosmotic exposure induced, within 1 hour, CD95 trafficking to the plasma
      membrane followed by activation of caspase-3 and -8. Hyperosmotic CD95 membrane
      targeting was sensitive to inhibition of c-Jun-N-terminal kinase (JNK), protein
      kinase C (PKC), and cyclic adenosine monophosphate, but not to inhibition of
      extracellular regulated kinases (Erks) or p38 mitogen activated protein kinase
      (p38(MAPK)). Hyperosmotic CD95 targeting to the plasma membrane was dose
      dependently diminished by glutamine or taurine, probably caused by an
      augmentation of volume regulatory increase. Despite CD95 trafficking to the
      plasma membrane and caspase activation, hyperosmolarity per se did not induce
      apoptosis. Hyperosmolarity, however, sensitized hepatocytes toward CD95L-induced
      apoptosis, as assessed by annexin V staining and terminal deoxynucleotidyl
      transferase-mediated X-dUTP nick-end labeling (TUNEL) assay. This sensitization
      was abolished when hyperosmotic CD95 membrane trafficking was prevented by cyclic
      adenosine monophosphate, PKC, or JNK inhibition, whereas these effectors had no
      effect on CD95L-induced apoptosis in normoosmotically exposed hepatocytes. CD95L
      addition under normoosmotic conditions caused CD95 membrane trafficking, which
      was sensitive to JNK inhibition, but not to cyclic adenosine monophosphate or
      inhibition of PKC, Erks, and p38(MAPK). In conclusion, multiple signaling
      pathways are involved in CD95 membrane trafficking. Hyperosmotic hepatocyte
      shrinkage induces CD95 trafficking to the plasma membrane, which involves JNK-,
      PKA-, and PKC-dependent mechanisms and sensitizes hepatocytes toward CD95L
      mediated apoptosis.

PMID- 12198653
TI  - Apoptosis of human hepatic myofibroblasts promotes activation of matrix
      metalloproteinase-2.
AB  - Liver fibrosis is potentially reversible after removal of the injurious agent.
      Fibrosis resolution is characterized by apoptosis of hepatic myofibroblasts and
      degradation of extracellular matrix components. Matrix metalloproteinase-2 (MMP
      2) is involved in matrix remodeling. In the liver, it is synthesized by
      myofibroblasts, secreted as a proenzyme, and activated by membrane type-MMPs (MT
      MMP) such as MT1-MMP. The goal of this work was to determine whether apoptosis
      induction in human hepatic myofibroblasts modulates the gene expression of MMP-2
      and/or its activation by MT1-MMP. Induction of apoptosis by cytochalasin D or
      C(2)-ceramide did not modulate MMP-2 mRNA expression. In contrast, apoptosis was
      associated with marked activation of pro-MMP-2, as shown by gelatin zymography,
      which revealed the presence of the 59-kd active form, whereas untreated cells
      only expressed the 66-kd proform. SB-203580, a specific inhibitor of p38 (MAPK),
      selectively abrogated both C(2)-ceramide-induced apoptosis and pro-MMP-2
      activation. Apoptosis-induced pro-MMP-2 activation was inhibited by the tissue
      inhibitors of metalloproteinases (TIMP)-2 but not by TIMP-1, implying involvement
      of an MT-MMP-mediated process. Induction of apoptosis by cytochalasin D and C(2)
      ceramide upregulated MT1-MMP protein expression and MT1-MMP mRNA expression. In
      conclusion, apoptosis of hepatic myofibroblasts induces pro-MMP-2 activation
      through increased MT1-MMP expression. HEPATOLOGY 2002;36:615-622.)

PMID- 12198654
TI  - Demonstration of direct lineage between hepatocytes and hepatocellular carcinoma
      in diethylnitrosamine-treated rats.
AB  - The question whether hepatocellular carcinoma (HCC) arises from dedifferentiation
      of mature hepatocytes or from proliferation of liver stem cells is still debated.
      In the present study, we used retroviral-mediated genetic labeling to investigate
      the fate of mature hepatocytes in rats after administration of diethylnitrosamine
      (DEN). Mature hepatocytes were genetically labeled by intravenous injection of
      retroviral vectors containing the Escherichia coli beta-galactosidase gene
      coupled to a nuclear localization signal (nls-LacZ) 1 day after partial
      hepatectomy. Liver biopsies performed after completion of hepatic regeneration
      showed that 18.3% of hepatocytes expressed the nls-LacZ transgene. Rats were then
      treated with DEN in drinking water for 12 weeks and sacrificed between 98 and 151
      days after the onset of DEN administration. Clones of beta-galactosidase positive
      cells were observed, half of which (53%) also expressed the placental form of
      glutathione-S-transferase (GSTp), a marker of preneoplastic cells. HCCs of
      various sizes expressing GSTp were present in all animals. Careful examination of
      90 HCCs revealed that 16 (17.7%) also expressed nls-LacZ. This figure precisely
      matched the proportion of labeled hepatocytes before DEN treatment (18.3%). In
      conclusion, a random clonal origin of HCC from mature hepatocytes is seen in the
      DEN model of hepatocarcinogenesis.

PMID- 12198655
TI  - Expression and regulation of gap junctions in rat cholangiocytes.
AB  - Hepatocytes and other digestive epithelia exchange second messengers and
      coordinate their functions by communicating through gap junctions. However,
      little is known about intercellular communication in cholangiocytes. The aim of
      this study was to examine expression and regulation of gap junctions in
      cholangiocytes. Connexin expression was determined by confocal immunofluorescence
      in rat bile ducts and in normal rat cholangiocyte (NRC) cells, a polarized
      cholangiocyte cell line. Intercellular Ca(2+) signaling was monitored by
      fluorescent microscopy. Microinjection studies assessed regulation of gap
      junction permeability in NRC cells and in SKHep1 cells, a liver-derived cell line
      engineered to express connexin 43. Immunochemistry showed that cholangiocytes
      from normal rat liver as well as the NRC cells express connexin 43. Localization
      of apical, basolateral, and tight junction proteins confirmed that NRC cells are
      well polarized. Apical exposure to ATP induced Ca(2+) oscillations that were
      coordinated among neighboring NRC cells, and inhibition of gap junction
      conductance desynchronized the Ca(2+) oscillations. NRC cells transfected with a
      connexin 43 antisense were significantly less coupled. Transcellular dye
      spreading was inhibited by activation of protein kinase A or protein kinase C.
      The same was observed in transfected SKHep1 cells, which expressed only connexin
      43. Rat cholangiocytes and NRC cells express connexin 43, which permits
      synchronization of Ca(2+) signals among cells. Permeability of connexin 43-gap
      junctions is negatively regulated by protein kinases A and C. In conclusion,
      cholangiocytes have the capacity for intercellular communication of second
      messenger signals via gap junctions in a fashion that is under hormonal control.

PMID- 12198656
TI  - Insulin inhibits secretin-induced ductal secretion by activation of PKC alpha and
      inhibition of PKA activity.
AB  - Insulin stimulates canalicular bile flow by interaction with hepatocytes. Insulin
      regulates the function of a number of epithelia through activation and membrane
      translocation of Ca(2+)-dependent PKC isoforms. No information exists regarding
      insulin regulation of ductal bile secretion. The aim of the study was to
      determine the role and mechanisms of action of insulin in the regulation of
      cholangiocyte secretion in BDL rats. We determined the subcellular localization
      of insulin receptor in cholangiocytes. We measured the effect of insulin on (1)
      secretin-stimulated cAMP levels in cholangiocytes and duct expansion in
      intrahepatic bile duct units (IBDUs) in the absence or presence of BAPTA/AM, H7
      or rottlerin and (2) bile flow. We evaluated (1) if insulin effects are
      associated with activation of PKC alpha and (2) if activation of PKC causes
      inhibition of secretin-stimulated cAMP levels and PKA activity. We found insulin
      receptors only in the apical domain of cholangiocytes. Insulin inhibited secretin
      induced choleresis and secretin-stimulated cholangiocyte cAMP levels. Insulin
      inhibited secretin-induced secretion in IBDUs when applied at the basolateral
      membrane or microinjected into IBDU lumen. Insulin inhibitory effects on
      cholangiocyte secretion were blocked by BAPTA/AM and H7. Insulin induced
      activation of PKC alpha, which decreased secretin-stimulated cAMP and PKA
      activity. In conclusion, insulin inhibited secretin-induced ductal secretion of
      BDL rats through activation of PKC and inhibition of secretin-stimulated cAMP and
      PKA activity. In conclusion, insulin counter-regulates cholangiocyte secretory
      processes in the BDL model, which is characterized by cholangiocyte
      proliferation.

PMID- 12198657
TI  - Novel fibrinogen gamma375 Arg-->Trp mutation (fibrinogen aguadilla) causes
      hepatic endoplasmic reticulum storage and hypofibrinogenemia.
AB  - The proposita and her sister had chronically elevated liver function test
      results, and needle biopsy specimens showed scattered eosinophilic inclusions
      within the hepatocytes. On immunoperoxidase staining, the inclusions reacted
      strongly with anti-fibrinogen antisera; on electron-microscopic (EM) examination,
      the material appeared confined to the endoplasmic reticulum (ER) and was densely
      packed into tubular structures with a swirling fingerprint appearance.
      Coagulation investigations showed low functional and antigenic fibrinogen
      concentrations that were indicative of hypofibrinogenemia. Amplification and DNA
      sequencing showed a heterozygous CGG-->TGG mutation at codon 375 of the
      fibrinogen gamma chain gene. This novel gamma375 Arg-->Trp substitution
      segregated with hypofibrinogenemia in 3 family members and was absent from 50
      normal controls. When purified plasma fibrinogen chains were examined by sodium
      dodecyl sulfate/polyacrylamide gel electrophoresis, reverse-phase chromatography,
      electrospray ionization mass spectrometry, and isoelectric focusing, only normal
      gamma chains were detected. In conclusion, we propose that this nonconservative
      mutation causes a conformational change in newly synthesized molecules and that
      this provokes aggregation within the ER and in turn causes the observed
      hypofibrinogenemia. Whereas the mutation site, gamma375, is located in the gammaD
      domain at the jaws of the primary E-to-D polymerization site, purified plasma
      fibrinogen showed normal polymerization, supporting our contention that molecules
      with variant chains never reach the circulation but accumulate in the ER.

PMID- 12198658
TI  - Serum phosphate is an early predictor of outcome in severe acetaminophen-induced
      hepatotoxicity.
AB  - Hypophosphatemia is frequently observed in acetaminophen-induced hepatotoxicity
      and may be involved in the pathogenesis of hepatic failure. The aim of the study
      was to evaluate the prognostic value of serial measurements of serum phosphate in
      patients with severe acetaminophen poisoning. Prospectively, serial measurements
      of serum phosphate were performed in 125 patients with severe acetaminophen
      poisoning. The optimum threshold value of serum phosphate to discriminate
      nonsurvivors was identified. Prognostic value and speed of identification were
      compared with those of the King's College Hospital (KCH) criteria. Phosphate
      concentrations were significantly higher in nonsurvivors than in survivors at 48
      to 72 hours after overdose (mean 2.65 +/- 1.18 mmol/L vs. 0.68 +/- 0.22 mmol/L, P
      <.001) as well as 72 to 96 hours after overdose (2.12 +/- 0.22 mmol/L vs. 0.59 +/
      0.23 mmol/L, P <.001). A threshold phosphate concentration of 1.2 mmol/L at 48
      to 96 hours after overdose had sensitivity 89%, specificity 100%, accuracy 98%,
      positive predictive value 100%, and negative predictive value 98%. The phosphate
      criteria had higher sensitivity, accuracy, and positive and negative predictive
      values than the KCH criteria, and it identified patients significantly earlier
      after transferal [median 1 hour (range 1-38 hours) vs. 12 hours (2-192 hours), P
      <.05, respectively]. In nonsurvivors, the degree of hyperphosphatemia correlated
      with renal dysfunction (R =.55; P =.02). In conclusion, hyperphosphatemia after
      acetaminophen overdose is seen exclusively in nonsurvivors, which makes it a
      highly specific as well as sensitive predictor of nonsurvival. We propose that
      hyperphosphatemia is caused by renal dysfunction in the absence of hepatic
      regeneration, as the latter appears to be associated with lowering of serum
      phosphate.

PMID- 12198659
TI  - Endoscopic ligation compared with sclerotherapy for bleeding esophageal varices
      in children with extrahepatic portal venous obstruction.
AB  - Endoscopic sclerotherapy is an effective treatment for bleeding esophageal
      varices, but it is associated with significant complications. Endoscopic
      ligation, a new form of endoscopic treatment for bleeding varices, has been shown
      to be superior to sclerotherapy in adult patients with cirrhosis. To determine
      the efficacy and safety of endoscopic sclerotherapy and ligation, the 2 methods
      were compared in a randomized control trial in 49 children with extrahepatic
      portal venous obstruction who had proven bleeding from esophageal varices. Twenty
      four patients were treated with sclerotherapy and 25 with band ligation. No
      significant differences were found between the sclerotherapy and ligation groups
      in arresting active index bleeding (100% each) and achieving variceal eradication
      (91.7% vs. 96%, P =.61). Band ligation eradicated varices in fewer endoscopic
      sessions than did sclerotherapy (3.9 +/- 1.1 vs. 6.1 +/- 1.7, respectively, P
      <.0001). The rebleeding rate was significantly higher in the sclerotherapy group
      (25% vs. 4%, P =.049), as was the rate of major complications (25% vs. 4%, P
      =.049). After eradication, esophageal variceal recurrence was not significantly
      different in patients treated by ligation than by sclerotherapy (17.4% vs. 10%, P
      =.67). In conclusion, variceal band ligation in children is a safe and effective
      technique that achieves variceal eradication more quickly, with a lower
      rebleeding rate and fewer complications compared with sclerotherapy.

PMID- 12198660
TI  - Noninvasive prediction of cirrhosis in C282Y-linked hemochromatosis.
AB  - The aim of the present study was to examine the predictive accuracy of
      noninvasive clinical and biochemical variables associated with cirrhosis among
      patients with C282Y homozygous hemochromatosis. Sixteen clinical and laboratory
      variables were recorded at the time of diagnosis in 193 Canadian C282Y homozygous
      patients. All patients underwent percutaneous liver biopsy and 27 (14%) had
      biopsy specimen-proven cirrhosis. Prediction of cirrhosis was assessed first by
      univariate regression analysis. Variables significantly related to cirrhosis were
      then evaluated by stepwise linear multivariate regression. Receiver operating
      characteristic curve analysis of the most informative variables from multivariate
      analysis was then used to devise a clinically applicable index for the
      noninvasive prediction of cirrhosis. This index was then validated in 162 C282Y
      homozygous patients in France. Ferritin, blood platelets, and aspartate
      transaminase (AST) level were selected for the clinical index. The combination of
      ferritin levels of 1,000 microg/L or greater, platelet levels of 200 x 10(9)/L or
      less, and AST levels above the upper limit of normal led to a correct diagnosis
      of cirrhosis in 77% of Canadian patients. In the French patients, this led to a
      correct diagnosis of cirrhosis in 90%. In conclusion, in C282Y homozygous
      patients, a combination of easily measured laboratory variables (ferritin,
      platelets, AST) can be used to make the diagnosis of cirrhosis in approximately
      81% of cases, reducing the need for liver biopsy.

PMID- 12198661
TI  - Bacterial motif DNA as an adjuvant for the breakdown of immune self-tolerance to
      pyruvate dehydrogenase complex.
AB  - Bacterial DNA containing unmethylated CpG dinucleotide motifs is
      immunostimulatory to mammals, skewing CD4(+) T-cell responses toward the Th1
      phenotype. Autoreactive T-cell responses seen in primary biliary cirrhosis (PBC)
      are typically of the Th1 phenotype, raising the possibility that bacterial DNA
      might play a role in the generation of pathologic autoimmunity. We therefore
      studied the effects of CpG motif-containing oligodeoxynucleotides (ODN) on
      responses to pyruvate dehydrogenase complex (PDC, the autoantigen in PBC) in a
      murine model. Sensitization of SJL/J mice with non-self-PDC has been shown to
      result in induction of autoreactive T-cell responses to PDC sharing
      characteristics with those seen in patients with PBC. Administration of CpG ODN
      to SJL/J mice at the time of sensitization with PDC resulted in a significant
      skewing of splenic T-cell response to self-PDC, with significant augmentation of
      the Th1 cytokine response (interleukin [IL] 2 and interferon [IFN] gamma) and
      reduction of the Th2 response (IL-4 and IL-10). In fact, CpG ODN seemed to be
      more effective at biasing the response phenotype and as effective at inducing
      liver histologic change as complete Freund's adjuvant (CFA), the standard
      adjuvant used for induction of Th1 responses in murine autoimmune and infectious
      immunity models. In conclusion, our findings raise the possibility that bacteria
      play a role in the development of autoimmunity (in PBC at least) through the
      potential of their DNA to shift the T-cell responses toward the phenotype
      associated with autoimmune damage. Moreover, this study suggests caution in the
      therapeutic use of CpG ODN as vaccine adjuvants.

PMID- 12198662
TI  - A randomized placebo-controlled study of long-acting octreotide for the treatment
      of advanced hepatocellular carcinoma.
AB  - Although various types of treatment of hepatocellular carcinoma (HCC) have been
      tried, the prognosis remains dismal, especially in patients with advanced stage
      of the disease. Somatostatin analogues exert antitumor effects. HCC have been
      shown to exhibit somatostatin receptors. The present randomized placebo
      controlled study aimed at examining the efficacy of long-acting octreotide
      (Sandostatin LAR) for the treatment of advanced HCC. Seventy patients were
      randomized to receive a 2-week course of 250 microg short-acting octreotide twice
      daily followed by Sandostatin LAR 30 mg injection once every 4 weeks for 6 doses
      (n = 35) or placebo (control group) (n = 35). The clinical and laboratory
      parameters were monitored. There was no difference in the cumulative survival
      between the Sandostatin LAR-treated group compared with the control group [median
      survival 1.93 months vs. 1.97 months, respectively, P = NS (log-rank test)].
      There was no tumor regression and no reduction of alpha-fetoprotein (AFP) levels
      in patients receiving Sandostatin LAR treatment. There was no improvement of
      quality of life assessed by Karnofsky performance score. In conclusion,
      Sandostatin LAR monotherapy did not have survival benefit in our selected group
      of patients with advanced HCC. Further studies should be performed in patients
      with less advanced disease and/or different etiology to evaluate its benefit.

PMID- 12198663
TI  - Altered expression of E-cadherin in hepatocellular carcinoma: correlations with
      genetic alterations, beta-catenin expression, and clinical features.
AB  - E-cadherin is a key cell adhesion protein implicated as a tumor/invasion
      suppressor in human carcinomas and a binding partner of beta-catenin, which plays
      a critical role in Wnt signaling and in tumorigenesis. Here we report genetic and
      expression studies of E-cadherin and beta-catenin in hepatocellular carcinoma
      (HCC). Immunohistochemical analysis of E-cadherin expression in 37 HCCs and
      adjacent nontumor tissues revealed important variations among tumor samples,
      ranging from complete or heterogeneous down-regulation in 35% of cases to marked
      overexpression in 40% of tumors. Loss of E-cadherin expression was closely
      associated with loss of heterozygosity (LOH) at the E-cadherin locus and
      methylation of CpG islands in the promoter region (P <.002), predominantly in
      hepatitis B virus (HBV)-related tumors (P <.005). No mutation of the E-cadherin
      gene could be detected in the tumors examined, suggesting the requirement for
      reversible mechanisms of E-cadherin down-regulation. In most HCCs, including E
      cadherin-positive and -negative cases, beta-catenin was strongly expressed at the
      cell membrane and nuclear accumulation of the protein was correlated with the
      presence of mutations in the beta-catenin gene itself, but not with E-cadherin
      loss. At difference with a number of epithelial cancers, vascular invasion was
      frequently noted in HCCs showing enforced expression of the membranous E
      cadherin/beta-catenin complex. In conclusion, these data support the notion that
      E-cadherin might play diverse and seemingly paradoxic roles in HCC, reflecting
      specific requirements for tumor growth and spread in the liver environment.

PMID- 12198664
TI  - Preemptive use of lamivudine reduces hepatitis B exacerbation after allogeneic
      hematopoietic cell transplantation.
AB  - Exacerbation of hepatitis B virus (HBV) is a serious cause of morbidity and
      mortality in hepatitis B surface antigen (HBsAg)-positive patients undergoing
      transplantation. Our aim was to evaluate the effectiveness of lamivudine to
      prevent hepatitis due to exacerbation of HBV in HBsAg-positive patients treated
      with allogeneic hematopoietic cell transplantation. We studied 20 consecutive
      HBsAg-positive recipients of allogeneic hematopoietic cell transplantation who
      received lamivudine 100 mg daily starting one week before transplantation until
      week 52 after transplantation (group 1). Serial serum alanine aminotransferase
      and HBV DNA levels were measured before and after transplantation at 4- to 8-week
      intervals for the first year and then 4- to 12-week intervals. Their virologic
      and clinical outcomes were compared with 20 case-matched recipients who did not
      receive any antiviral therapy to HBV (anti-HBV) before and after hematopoietic
      cell transplantation (group 2). After transplantation, 9 patients (45%) in group
      2 and one patient (5%) in group 1 had hepatitis due to exacerbation of HBV (P
      <.008), with 3 hepatic failures in group 2 and none in group 1. The one-year
      actuarial probability of survival without hepatitis due to exacerbation of HBV
      was higher in group 1 than group 2 (94.1% vs. 54.3%, P =.002). By multivariate
      Cox analysis, preemptive use of lamivudine effectively reduced hepatitis due to
      exacerbation of HBV (adjusted hazards ratio, 0.09; P =.021). In conclusion,
      preemptive lamivudine reduced HBV exacerbation. The use of lamivudine with other
      immunosuppressive regimens to prevent exacerbation of HBV should be further
      explored.

PMID- 12198665
TI  - Inhibitory activity of dioxolane purine analogs on wild-type and lamivudine
      resistant mutants of hepadnaviruses.
AB  - To design combination strategies for chronic hepatitis B therapy, we evaluated in
      vitro the inhibitory activity of 4 nucleoside analogs, (-)FTC, L-FMAU, DXG, and
      DAPD, in comparison with lamivudine (3TC) and PMEA. In a cell-free assay for the
      expression of wild-type duck hepatitis B virus (DHBV) reverse transcriptase, DAPD
      TP was found to be the most active on viral minus strand DNA synthesis, including
      the priming reaction, followed by 3TC-TP, (-)FTC-TP, and DXG-TP, whereas L-FMAU
      TP was a weak inhibitor. In cell culture experiments, important differences in
      drug concentration allowing a 50% inhibition of viral replication or polymerase
      activity (IC50s) were observed depending on the cell type used, showing that
      antiviral effect of nucleoside analogs may depend on their intracellular
      metabolism. IC50s obtained for wild-type DHBV replication in primary duck
      hepatocytes were much lower than with DHBV transfected LMH cells. IC50s were also
      significantly lower in the 2.2.1.5 and HepG2 cells compared with HBV transfected
      HuH7 cells. Moreover, L-FMAU inhibited preferentially HBV plus strand DNA
      synthesis in these cell lines. The antiviral effect of these inhibitors was also
      evaluated against 3TC-resistant mutants of the DHBV and HBV polymerases. These
      mutants were found to be cross resistant to (-)FTC. By contrast, the double DHBV
      polymerase mutant was sensitive to DXG-TP and DAPD-TP. Moreover, both purine
      analogs remained active against DHBV and HBV 3TC-resistant mutants in transfected
      LMH and HepG2 cells, respectively. In conclusion, the unique mechanism of action
      of these new inhibitors warrants further evaluation in experimental models to
      determine their capacity to delay or prevent the selection of drug resistant
      mutants.

PMID- 12198666
TI  - Rapid detection of hepatitis B virus mutations using real-time PCR and melting
      curve analysis.
AB  - Current methods of detecting hepatitis B virus (HBV) mutations are time
      consuming, labor intensive, and not suitable for screening large numbers of
      samples. In the present study, we documented the advantages of a system that
      exploits differences in thermal stability between perfect match and mismatch
      hybrids, and thereby distinguishes between wild-type and mutants. Hybridization
      probes were designed complementary to specific wild-type HBV sequences in surface
      (S), precore, and basal core promoter (BCP) regions of the HBV genome (nt 587,
      1896, and 1762/1764, respectively). Two probes were designed for each mutation:
      anchor probes were 3' labeled with fluorescein and sensor probes, 5' labeled with
      LC-Red 640, and 3' phosphorylated. Temperatures for each probe melted from
      amplification products were then determined in a melting program. Sera from 12
      patients, each containing identified HBV mutants (6 S-escape, 1 precore, 1 BCP,
      and 4 mixed precore and BCP), and 5 control sera from patients with wild-type
      virus were analyzed. Genomic sequences of mutant and wild-type viruses were
      confirmed by direct sequencing. Real-time polymerase chain reaction (PCR) with
      fluorescent hybridization probes accurately identified each mutant and wild-type
      genome. Melting temperatures obtained from probe-product duplexes for the 3
      mutants were distinguished from wild-type (>4.0 degrees C, minimal) within 45
      minutes. The sensitivity of the system was 100 copies/mL and as few as 5% of
      mutant among wild-type virus were detected. In conclusion, real-time PCR with
      fluorescent hybridization probes is a specific, sensitive, quantitative, and
      rapid means of detecting clinically relevant HBV mutants.

PMID- 12198667
TI  - Steatosis in chronic hepatitis C: relative contributions of obesity, diabetes
      mellitus, and alcohol.
AB  - Steatosis has emerged as a histologic finding of importance to the progression of
      hepatitis C virus (HCV)-associated liver disease. However, most studies of HCV
      associated steatosis have excluded alcohol drinkers and individuals with diabetes
      and thus have not addressed the relative contribution of known causes of
      steatosis to liver injury in HCV-associated disease. To address this issue, we
      studied 297 consecutive patients with HCV who met inclusion criteria. Alcohol
      consumption, demographics, and serologic tests were correlated with degrees of
      steatosis and fibrosis on liver biopsy. Liver biopsy specimens were also examined
      for evidence of significant alcohol or nonalcoholic steatohepatitis (NASH)
      injury. In univariate analysis, steatosis correlated with type 2 diabetes
      mellitus (P =.005) and body mass index (BMI) (P =.0001) but not with the
      intensity of alcohol intake (in grams per day). In multivariate analysis, BMI (P
      =.0002) and genotype 3a infection (P =.02) were independent predictors of
      steatosis. When patients with risk factors for NASH were excluded, genotype 3a
      infection was the only independent predictor of steatosis. Steatosis (P =.04) and
      inflammation (P <.0001) scores on liver biopsy were the only independent
      predictors of fibrosis. Significant alcohol or NASH injury was found in only 6%
      of biopsy specimens. In conclusion, steatosis in HCV infection is associated with
      risk factors for NASH, particularly obesity, rather than alcohol consumption.

PMID- 12198668
TI  - Opportunities for prevention: hepatitis C prevalence and incidence in a cohort of
      young injection drug users.
AB  - The objective of this study was to compare sociodemographic, drug, and sexual
      risk characteristics between hepatitis C virus (HCV) baseline positive and
      negative young (13-24 years) injection drug users (IDUs) and to determine
      prospective risk factors for HCV seroconversion among the youth. Data were
      collected through the Vancouver Injection Drug Users Study (VIDUS). To date, more
      than 1,400 Vancouver-area IDUs have been enrolled and followed up; 234 were aged
      24 years and younger. Semiannually, participants have completed an interviewer
      administered questionnaire and have undergone serologic testing for human
      immunodeficiency virus (HIV) and HCV. Univariate and multivariate logistic
      regression analyses were undertaken to investigate predictors of baseline HCV
      positivity. In the multivariate analyses, Cox regression models with time
      dependent covariates were used to identify predictors of HCV seroconversion. Of
      the 232 young injectors, 107 (46%) were HCV positive at baseline and a further 37
      HCV seroconverted during the study period for an incidence rate of 37.3 per 100
      person-years. Baseline positivity was associated with Aboriginal ancestry, older
      age, greater number of years injecting drugs, recent incarceration, sex trade
      work, more than 100 lifetime sexual partners, a previous sexually transmitted
      disease, living in the IDU epicenter, and injection more than once per day of
      heroin, cocaine, and speedball. Factors independently associated with HCV
      seroconversion were having a partner who uses injection drugs, requiring help to
      inject, and injection of cocaine more than once daily. In conclusion, unlike
      older IDUs, more than one half of young injectors were HCV negative at
      recruitment. Thus, there is a window of opportunity for prevention. However, the
      incidence rate of HCV among these young IDUs is alarming, suggesting that the
      opportunity to intervene is exceedingly small.

PMID- 12198670
TI  - Ca2+: the clue to hepatitis B virus X protein function?

PMID- 12198669
TI  - The dynamics of T-lymphocyte responses during combination therapy for chronic
      hepatitis C virus infection.
AB  - Hepatitis C virus (HCV) readily sets up a persistent infection and is a major
      cause of liver disease worldwide. Interferon alfa and ribavirin therapy lead to
      sustained clearance of virus in 31% to 64% of patients with type 1 and non-type 1
      genotypes, respectively. It is not clear to what extent these drugs act directly
      to reduce HCV replication, or indirectly via host immune responses, and what
      evoked immune responses are associated with clinical outcome. We have examined
      prospectively 15 patients with chronic HCV infection before, during, and after
      combination therapy. Quantitative assays for HCV antigen-specific CD4+ and CD8+ T
      cell responses, and flow cytometric assays for analysis of the phenotype of T
      cells, in addition to viral sequencing of core protein, were performed throughout
      the treatment and follow-up period over 18 months. We found enhancement of
      proliferative T-cell responses during therapy. Proliferative responses are
      strikingly heterogeneous in terms of specificity, kinetics, and magnitude.
      Proliferative responses are often not associated with interferon-gamma release. T
      cell responses are rarely sustained irrespective of treatment outcome and this is
      not due to the evolution of new immune escape variants. T-cell responses tend to
      peak late in the course of treatment. In conclusion, combination therapy for HCV
      has a transient effect on host virus-specific T cells in the blood. Induction of
      sustained T-cell responses may require additional immune modulation later in
      therapy.

PMID- 12198671
TI  - Reading between the lines: evidence for a new hepatitis C virus protein.

PMID- 12198672
TI  - Xanthine oxidase-induced oxidant stress during hepatic ischemia-reperfusion: are
      we coming full circle after 20 years?

PMID- 12198673
TI  - Hemolysis in Gilbert's syndrome.

PMID- 12198675
TI  - Prevalence and clinical relevance of anti-soluble liver antigen (SLA) antibodies
      in autoimmune hepatitis.

PMID- 12198677
TI  - Quality of life with pegylated interferon therapy for hepatitis C.

PMID- 12198678
TI  - International hepatology.

PMID- 12198682
TI  - The thin red line.

PMID- 12198685
TI  - AGA a key to HELP committee passage of colorectal cancer screening expansion.
      American Gastroenterological Association.

PMID- 12198686
TI  - NIH set to expand digestive diseases study section.

PMID- 12198687
TI  - AGA research policy initiatives.

PMID- 12198689
TI  - The real meaning of translational research.

PMID- 12198688
TI  - Increased need for PhDs in gastrointestinal research.

PMID- 12198690
TI  - Image of the month. Pyogenic liver abscess complicated by bronchial fistula.

PMID- 12198691
TI  - Paradoxical coexpression of proinflammatory and down-regulatory cytokines in
      intestinal T cells in childhood celiac disease.
AB  - BACKGROUND & AIMS: Specific T-lymphocyte reactions are central in the
      pathogenesis of celiac disease, an inflammatory small-bowel enteropathy caused by
      a permanent intolerance to gluten. To delineate local T-lymphocyte responses to
      gluten, the cytokine expression in jejunal T lymphocytes of pediatric celiac
      patients with active disease, i.e., untreated and gluten-challenged celiac
      patients, was determined and compared with that of treated, symptom-free celiac
      patients and controls. METHODS: Biopsy samples were collected from celiac
      patients and controls. Intraepithelial and lamina propria T lymphocytes were
      isolated separately, and the cytokine messenger RNA levels were determined by
      using quantitative real-time reverse-transcription polymerase chain reaction.
      Interferon (IFN)-gamma and interleukin (IL)-10 were determined at the protein
      level by immunohistochemistry. RESULTS: Active celiac disease was characterized
      by distortions in cytokine expression by T lymphocytes, with highly significant
      increases of IFN-gamma and IL-10 but no concomitant increases in tumor necrosis
      factor alpha, transforming growth factor beta1, or IL-2 and no induction of IL-4.
      A marked shift of IFN-gamma and IL-10 production from the lamina propria to the
      epithelium was characteristic of active celiac disease, and as many as one fourth
      of the intraepithelial lymphocytes expressed IFN-gamma. Intraepithelial T
      lymphocytes in treated, symptom-free celiac patients still had increased IFN
      gamma levels compared with controls. CONCLUSIONS: In celiac patients, gluten
      intake seems to cause an overreaction in intraepithelial T lymphocytes, with
      uncontrolled production of IFN-gamma and IL-10. This may cause both recruitment
      of intraepithelial lymphocytes and a leaky epithelium, leading to a vicious
      circle with amplified immune activity and establishment of intestinal lesions.

PMID- 12198692
TI  - Mutations in NOD2 are associated with fibrostenosing disease in patients with
      Crohn's disease.
AB  - BACKGROUND & AIMS: The clinical manifestations of Crohn's disease (CD) are
      diverse, ranging from fibrostenosing small-bowel disease to colon-predominant
      inflammation. These distinctions may represent genetic, immunologic, and
      microbial heterogeneity. NOD2 gene mutations in CD have been described recently
      and may alter innate immune responses. We hypothesized that NOD2 mutations may be
      associated with distinct phenotypic expressions of CD. METHODS: Two cohorts of
      consecutively identified patients referred to an inflammatory bowel disease
      center (n = 142 collected between 1993 and 1996; n = 59 collected between 1999
      and 2001) were genotyped for 3 single nucleotide variants of NOD2-R675W, G881R,
      and 3020insC-and phenotyped for disease behavior, disease location, and serum
      immune markers. RESULTS: Univariate analysis showed that CD-associated NOD2
      variants were significantly associated with fibrostenosing disease in each cohort
      (P = 0.049 and P = 0.002, respectively). When both cohorts were analyzed
      together, the association between NOD2 variants and fibrostenosing disease was
      more significant (P = 0.001). These relationships were observed in both Jews and
      non-Jews. Forty-six percent of patients with fibrostenosing disease carried at
      least 1 of these alleles, compared with only 23.5% of patients without
      fibrostenosing disease (odds ratio, 2.8; 95% confidence interval, 1.6-5.2).
      Multivariate and conditioning analyses showed a primary association between NOD2
      allelic variants and fibrostenosing disease, but not with small-bowel disease.
      CONCLUSIONS: In this description of a genotype/phenotype correlation in CD
      patients and NOD2 variants, data suggest that variation in this gene contributes
      to the occurrence of fibrostenotic CD of the small bowel.

PMID- 12198694
TI  - Meigs of Meigs' syndrome.

PMID- 12198693
TI  - Selected loss of tolerance evidenced by Crohn's disease-associated immune
      responses to auto- and microbial antigens.
AB  - BACKGROUND & AIMS: Previous studies in Crohn's disease suggest global loss of
      tolerance with sonicated bacteria preparations containing hundreds of antigens.
      Monoassociation studies show that a solitary bacterium can induce colitis in one
      animal model, whereas another is responsible in other models. Among patients with
      Crohn's disease, serum responses have been documented to microbial and
      autoantigens (antibodies to the Escherichia coli outer-membrane porin C and the
      Pseudomonas fluorescens-associated sequence I2, antisaccharomyces cerevisiae
      antibody (ASCA), and perinuclear antineutrophil cytoplasmic antibodies). Our aim
      was to determine whether there are heterogeneous responses to these specific
      antigens. METHODS: Sera from 330 Crohn's patients were analyzed. Immunoglobulin A
      enzyme-linked immunosorbent assays to ASCA, outer-membrane porin C, or I2 and
      immunoglobulin G enzyme-linked immunosorbent assay to ASCA and ANCA determined
      the presence and level of antibodies. Perinuclear antineutrophil cytoplasmic
      antibodies were determined by immunofluorescence. RESULTS: ASCA was detected in
      56% of patients; 55% were seroreactive to outer-membrane porin C, 50% were
      seroreactive to I2, and 23% were perinuclear antineutrophil cytoplasmic antibody
      positive. Eighty-five percent responded to at least 1 antigen; only 4% responded
      to all 4. Among microbial antigens, 78% responded to at least 1, and 57% were
      double positive, but only 26% responded to all 3. The level of response was
      stable over time and with change in disease activity. Among patients with the
      same qualitative antigen-response profiles, quantitative response differed.
      Cluster analysis of these antibody responses yielded 4 groups: ASCA, outer
      membrane porin C/I2, perinuclear antineutrophil cytoplasmic antibodies, or no/low
      response. CONCLUSIONS: Rather than global loss of tolerance, there seem to be
      patient subsets with differing responses to selected microbial and autoantigens.

PMID- 12198695
TI  - Lipid-induced intestinal gas retention in irritable bowel syndrome.
AB  - BACKGROUND & AIMS: We hypothesized that lipids, which induce various motor and
      sensory effects on the gut, modulate intestinal gas dynamics and that alteration
      of this regulatory mechanism may result in impaired gas transit in patients with
      irritable bowel syndrome (IBS). METHODS: In 45 healthy subjects and 30 patients
      with IBS, evacuation of gas infused into the jejunum (at 12 mL/min) was measured
      for 2 hours. The effect of simultaneous duodenal perfusion of lipids at 0
      kcal/min (saline), 0.5 kcal/min, and 1 kcal/min was tested in groups of 15
      subjects each. RESULTS: In healthy subjects, duodenal lipids at 1 kcal/min but
      not at 0 kcal/min or 0.5 kcal/min produced significant gas retention (281 +/- 53
      mL vs. 22 +/- 64 mL at 0 kcal/min and -65 +/- 72 mL at 0.5 kcal/min; P < 0.05 for
      both). Patients with IBS exhibited gas retention during saline perfusion (259 +/-
      85 mL at 0 kcal/min; P < 0.05 vs. healthy subjects) and were hypersensitive to
      duodenal lipids (505 +/- 61 mL retention at 0.5 kcal/min; P < 0.05 vs. saline and
      vs. healthy subjects). The "gas plus lipids" challenge test discriminated
      patients with 100% sensitivity and 93% specificity. CONCLUSIONS: Physiologic
      concentrations of intestinal lipids exert an inhibitory control on intestinal gas
      transit, and this mechanism is up-regulated in patients with IBS. Hence, impaired
      gas propulsion, shown by the gas challenge test, may be useful as a diagnostic
      test if replicated in a larger series of patients.

PMID- 12198696
TI  - Predictors of response to infliximab in patients with Crohn's disease.
AB  - BACKGROUND & AIMS: Identifying predictors of response to infliximab in Crohn's
      disease may lead to better selection of patients for this therapy. METHODS: One
      hundred patients with either inflammatory or fistulous Crohn's disease and at
      least 3 months of follow-up after infliximab infusion were evaluated. Clinical
      response and duration of response were the primary outcome measures. RESULTS: For
      inflammatory disease, 73% of nonsmokers, compared with 22% of smokers, responded
      to infliximab (P < 0.001). Among patients taking concurrent immunosuppressives,
      74% responded to infliximab compared with 39% not taking any immunosuppressives
      (P = 0.007). Prolonged response (duration >2 months) was achieved in 59% of
      nonsmokers compared with 6% of smokers (P < 0.001) and in 65% of patients on
      immunosuppressives compared with 18% not on immunosuppressives (P < 0.001). For
      fistulous disease, overall response rates were not different between nonsmokers
      and smokers, but nonsmokers had a longer duration of response (P = 0.046).
      Concurrent use of immunosuppressive medications had no effect on rate or duration
      of response. Multivariable logistic regression analysis confirmed the harmful
      effect of smoking and the beneficial effect of immunosuppressive use on response
      in patients with inflammatory disease. The same analysis for fistulous disease
      did not show an association between smoking or concurrent immunosuppressive use
      and response to infliximab. CONCLUSIONS: In patients with inflammatory disease,
      nonsmoking and concurrent immunosuppressive use are associated with higher rates
      of response and longer duration of response to infliximab. In patients with
      fistulous Crohn's disease, nonsmoking is associated with longer duration of
      response to infliximab.

PMID- 12198697
TI  - Uveitis and erythema nodosum in inflammatory bowel disease: clinical features and
      the role of HLA genes.
AB  - BACKGROUND & AIMS: There are few systematic studies on the natural history or
      immunogenetic associations of erythema nodosum (EN) or ocular inflammation in
      inflammatory bowel disease (IBD), but they are reportedly more common in patients
      with other extraintestinal manifestations (EIMs), particularly arthritis.
      Immunogenetic associations have previously been described in IBD arthritis and in
      EN associated with sarcoidosis. This study examined the clinical features and HLA
      B, DR, and tumor necrosis factor alpha (TNF-alpha) associations of ocular
      inflammation and EN and their clinical and immunogenetic relationship to
      arthritis in IBD. METHODS: Details of EN and ocular inflammation were gathered by
      case-note review and questionnaire in 976 ulcerative colitis patients and 483
      Crohn's patients. Sequence-specific PCR typing for polymorphisms in HLA-B, DR,
      and TNF-alpha was performed in 39 EN and 40 ocular patients. Results were
      compared with 490 IBD controls without EIMs, 38 patients with type 1 and 31 with
      type 2 peripheral arthritis, and 16 AS patients. RESULTS: EN and ocular
      inflammation were more common in women, were associated with IBD relapse, and
      recurred in approximately 30% of patients. They occurred more commonly with
      arthritis and AS than expected by chance. Ocular inflammation was strongly
      associated with HLA-B*27, B*58, and HLA-DRB1*0103. There is a weak association
      between EN and HLA-B*15 but a strong association with the -1031 TNF-alpha.
      CONCLUSIONS: EN, uveitis, and arthritis associated with IBD occur together
      commonly. They are associated with genes in the HLA region, and linkage
      disequilibrium between these genes may account for the clinical picture of
      overlapping but independent clinical manifestations.

PMID- 12198698
TI  - Determinants of early mortality in patients with decompensated chronic hepatitis
      B treated with antiviral therapy.
AB  - BACKGROUND & AIMS: Chronic hepatitis B is a leading cause of death worldwide. To
      identify patients who might require urgent liver transplantation despite
      antiviral therapy, we investigated the determinants of early mortality in a large
      cohort of patients with decompensated chronic hepatitis B treated with
      lamivudine. METHODS: One hundred fifty-four North American patients with
      decompensated chronic hepatitis B received lamivudine for a median of 16 months.
      Univariate and multivariate Cox regression modeling was used to develop a model
      of 6-month mortality. RESULTS: A biphasic survival pattern was observed, with
      most deaths occurring within the first 6 months of treatment (25 of 32, 78%)
      because of complications of liver failure. The estimated actuarial 3-year
      survival of patients who survived at least 6 months was 88% on continued
      treatment. In multivariate modeling, elevated pretreatment serum bilirubin and
      creatinine levels as well as the presence of detectable hepatitis B virus (HBV)
      DNA (by the bDNA assay) pretreatment were significantly associated with 6-month
      mortality. An equation approximating the probability of early mortality was
      developed from these variables. CONCLUSIONS: Our data demonstrate a distinct
      alteration in the slope of the survival curve after 6 months of lamivudine
      treatment for decompensated chronic hepatitis B. An equation consisting of 3
      widely available pretreatment laboratory parameters was developed that can be
      used to predict the likelihood of early death in patients receiving lamivudine
      for decompensated chronic hepatitis B. These observations may help identify
      patients who can be stabilized with suppressive antiviral therapy vs. those who
      require urgent liver transplantation.

PMID- 12198699
TI  - Banding ligation versus nadolol and isosorbide mononitrate for the prevention of
      esophageal variceal rebleeding.
AB  - BACKGROUND & AIMS: beta-blockers and banding ligation are effective in the
      prevention of variceal rebleeding. However, the relative efficacy and safety
      remains unresolved. METHODS: One hundred twenty-one patients with a history of
      esophageal variceal bleeding were enrolled. Patients were randomized to undergo
      regular endoscopic variceal ligation (EVL group, 60 patients) until variceal
      obliteration, or drug therapy by using nadolol plus isosorbide mononitrate (N+I
      group, 61 patients) during the study period to prevent rebleeding. RESULTS: After
      a median follow-up period of 25 months, recurrent upper gastrointestinal bleeding
      developed in 23 patients in the EVL group and 35 patients in the N+I group (P =
      0.10). Recurrent bleeding from esophageal varices occurred in 12 patients (20%)
      in the EVL group and 26 patients (42%) in the N+I group (relative risk = 0.45;
      95% confidence interval, 0.24-0.85). The actuarial probability of rebleeding from
      esophageal varices was lower in the EVL group (P = 0.01). The multivariate Cox
      analysis indicated that the treatment was the only factor predictive of
      rebleeding. Treatment failure occurred in 8 patients (13%) in the EVL group and
      17 patients (28%) in the N+I group (P = 0.01). Fifteen patients in the EVL group
      and 8 patients of the N+I group died (P = 0.06). Complications occurred in 17% of
      the EVL group and in 19% of the N+I group (P = 0.6). CONCLUSIONS: Our trial
      showed that ligation was more effective than nadolol plus isosorbide-5
      mononitrate in the prevention of variceal rebleeding, with similar complications
      in both treatment modalities. However, there is no significant difference in the
      survival rate between the 2 groups.

PMID- 12198700
TI  - Primary prophylaxis of variceal hemorrhage: a randomized controlled trial
      comparing band ligation, propranolol, and isosorbide mononitrate.
AB  - BACKGROUND & AIMS: This randomized controlled trial compared variceal band
      ligation (VBL), propranolol (PPL), and isosorbide-5-mononitrate (ISMN) in the
      prevention of first esophageal variceal bleed. METHODS: Over a 6-year period, 172
      patients with cirrhosis, grade II or III esophageal varices that had never bled,
      were recruited; 44 into VBL, 66 into PPL, and 62 into ISMN. Baseline patient
      characteristics: age, 55 +/- 11 years; Child-Pugh score, 8 +/- 2; 65% alcohol
      induced cirrhosis; follow-up period, 19.7 +/- 17.6 months (range, 0.13-72.1
      months), were comparable in the 3 groups. RESULTS: On intention-to-treat
      analysis, variceal bleeding occurred in 7% of patients randomized to VBL, 14% to
      PPL, and 23% to ISMN. The 2-year actuarial risks for first variceal bleed were
      6.2% (95% confidence interval [CI], 0.0%-15.0%) for VBL, 19.4% (95% CI, 0.1%
      32.4%) for PPL, and 27.7% (95% CI, 14.2%-41.2%) for ISMN. A significant number of
      patients reported side effects with drug treatment (45% PPL and 42% ISMN vs. 2%
      VBL; P = 0.00), resulting in withdrawal from treatment in 30% of PPL and 21% of
      ISMN patients. There were no statistically significant differences in mortality
      rates in the 3 groups. In as-treated analysis, there was a statistically
      significant difference in actuarial risk for bleeding at 2 years between VBL and
      ISMN (7.5%, 95% CI, 2.5%-10.6% vs. 33.0%, 95% CI, 15%-49%, respectively, log rank
      test P = 0.03) but not between VBL and PPL. CONCLUSIONS: VBL was equivalent to
      PPL and superior to ISMN in preventing first variceal bleed. The side-effect
      profile for pharmacotherapy was considerable.

PMID- 12198701
TI  - The utility of radiological imaging in nonalcoholic fatty liver disease.
AB  - BACKGROUND & AIMS: This prospective study evaluates the role of radiological
      modalities in establishing the diagnosis of nonalcoholic steatohepatitis (NASH).
      METHODS: Consecutive patients with biopsy-proven nonalcoholic fatty liver disease
      (NAFLD) were enrolled (2000-2001). Patients with other liver diseases and
      significant alcohol consumption (>20 g/day) were excluded. Clinicodemographic
      data were gathered at the time of liver biopsy. Each biopsy specimen was assessed
      by a hepatopathologist. Each patient underwent a limited abdominal
      ultrasonography (US), computerized tomography (CT), and magnetic resonance
      imaging (MRI). Films were interpreted by a radiologist who used a predetermined
      radiological protocol. Each radiological study was reread by the same radiologist
      and a second radiologist. RESULTS: Patients with NASH had greater aspartate
      aminotransferase levels (P = 0.03), greater ferritin levels (P = 0.05), more
      hepatocyte ballooning (P < 0.0001), and more fibrosis (P = 0.002). None of the
      radiological features distinguished between NASH and other types of NAFLD. No
      radiological modality detected the presence of hepatocyte ballooning, Mallory's
      hyaline, or fibrosis, which are important features in the diagnosis of NASH. The
      presence of >33% fat on liver biopsy was optimal for detecting steatosis on
      radiological imaging. CONCLUSIONS: Differences between NASH and nonprogressive
      NAFLD were not apparent with any radiological modality. Of the pathologic
      features important for establishing the diagnosis of NASH, only the severity of
      steatosis was reflected in these radiological modalities. Good intraobserver
      agreement was evident for each modality (US, CT, and MRI) that was superior to
      interobserver agreement.

PMID- 12198702
TI  - The APC tumor suppressor controls entry into S-phase through its ability to
      regulate the cyclin D/RB pathway.
AB  - BACKGROUND & AIMS: APC gene mutation is an early alteration in most colorectal
      tumors. In an attempt to determine its role in tumor development, we asked
      whether reintroducing wild-type APC into colorectal cancer cells with mutant APC
      affected cell cycle progression. METHODS: Using transient transfection, a plasmid
      containing the APC complementary DNA and DNA encoding the green fluorescent
      protein was expressed in SW480 cells. In addition, several other constructs were
      co-expressed with APC to determine their combined effects. RESULTS: We report
      that colorectal cancer cell lines transfected with wild-type APC arrest in the
      G(1)- phase of the cell cycle and that this arrest is abrogated by cotransfecting
      constitutively active beta-catenin or cyclin D1 and cMYC together. This APC
      induced cell cycle arrest involves the disruption of beta-catenin-mediated
      transcription and depends on components of the G(1)/S regulatory machinery, as
      overexpression of E1a or E2F-1, -2, or -3 overrides the G(1) arrest. Consistent
      with this, APC transfection inhibits RB phosphorylation and reduces levels of
      cyclin D1. CONCLUSIONS: Our results suggest that APC functions upstream of RB in
      the G(1)/S regulatory pathway, cyclin D1 and cMYC affect APC-mediated arrest
      equivalently to oncogenic beta-catenin, and most colon tumors disrupt control of
      G(1)/S progression by APC mutation.

PMID- 12198703
TI  - JunD stabilization results in inhibition of normal intestinal epithelial cell
      growth through P21 after polyamine depletion.
AB  - BACKGROUND & AIMS: Normal intestinal mucosal growth requires cellular polyamines
      that regulate expression of various genes involved in cell proliferation, growth
      arrest, and apoptosis. We have recently shown that growth inhibition after
      polyamine depletion is associated with an increase in JunD/AP-1 activity in
      normal intestinal epithelial cells (IEC-6 line). The current study tests the
      hypothesis that polyamine depletion-induced JunD/activator protein 1 (AP-1)
      activity results from the activation of junD gene expression and plays a critical
      role in regulation of intestinal epithelial cell growth. METHODS: The junD gene
      transcription was examined by nuclear run-on assays, and messenger RNA (mRNA)
      stability was measured by determination of JunD mRNA half-life. Functions of JunD
      were investigated by using JunD antisense oligodeoxyribonucleotides and transient
      transfection with the junD-expressing vector. RESULTS: Depletion of cellular
      polyamines by DL-alpha-difluoromethylornithine (DFMO) induced levels of JunD mRNA
      and protein, which was associated with an increase in G(1) phase growth arrest.
      Polyamine depletion did not increase the rate of junD gene transcription but
      significantly increased the stability of JunD mRNA. Decreasing JunD protein by
      using JunD antisense oligomers promoted cell growth in polyamine-deficient cells.
      Growth arrest following polyamine depletion also was accompanied by increases in
      both p21 expression and its promoter activity. Treatment with JunD antisense
      oligomers inhibited the p21 promoter and prevented the increase in p21 expression
      in the presence of DFMO. Ectopic expression of the wild-type junD increased p21
      promoter activity and inhibited epithelial cell growth. CONCLUSIONS: Polyamines
      negatively regulate junD gene expression posttranscriptionally, and increased
      JunD/AP-1 inhibits intestinal epithelial cell proliferation at least partially
      through the activation of p21 promoter.

PMID- 12198704
TI  - Fas/CD95 is required for gastric mucosal damage in autoimmune gastritis.
AB  - BACKGROUND & AIMS: Experimental autoimmune gastritis (EAG), characterized by a
      gastric mononuclear cell infiltrate, mucosal cell damage, and autoantibodies to
      parietal cell-associated H(+)/K(+) adenosine triphosphatase, is a model for human
      autoimmune gastritis that leads to pernicious anemia. Previous in vitro studies
      have implicated Fas/CD95 in initiating damage to gastric mucosal cells in humans
      and an animal model of autoimmune gastritis. Here we used 2 in vivo animal models
      to examine the role of Fas in the development of mucosal cell damage in
      autoimmune gastritis. METHODS: We initiated EAG in BALB/cCrSlc mice by neonatal
      thymectomy and examined for Fas expression in the gastric mucosa by
      immunohistochemistry. To address the in vivo relevance of Fas in mucosal injury,
      we examined the stomachs and sera of BALB/cCrSlc lpr/lpr mice subjected to
      neonatal thymectomy and BALB/cCrSlc nu/nu lpr/lpr mice transferred with
      lymphocytes from gastritic BALB/cCrSlc mice. RESULTS: Fas expression was up
      reguiated in parietal cells of mice with EAG. Neonatally thymectomized lpr/lpr
      mice were resistant to developing destructive gastritis compared with
      heterozygous and wild-type littermates. Nu/nu Fas-sufficient mice transferred
      with lymphocytes from thymectomized lpr/lpr mice developed destructive gastritis.
      Nu/nu lpr/lpr mice transferred with lymphocytes from gastritic mice developed a
      nondestructive gastritis. CONCLUSIONS: The observations that Fas is up-regulated
      in gastric parietal cells of mice with EAG and that Fas-deficient mice are
      resistant to development of destructive gastritis provide compelling evidence
      that Fas is required in vivo for development of gastric mucosal cell damage in
      autoimmune gastritis.

PMID- 12198705
TI  - HMGB1 B box increases the permeability of Caco-2 enterocytic monolayers and
      impairs intestinal barrier function in mice.
AB  - BACKGROUND & AIMS: High mobility group (HMG) B1 is a nonhistone nuclear protein
      that was recently identified as a late-acting mediator of lipopolysaccharide
      induced lethality in mice. The proinflammatory actions of HMGB1 have been
      localized to a region of the molecule called the B box. METHODS: To determine
      whether HMGB1 or B box are capable of causing derangements in intestinal barrier
      function, we incubated cultured Caco-2 human enterocytic monolayers with
      recombinant human HMGB1 or a 74-residue truncated form of the protein consisting
      of the B box domain. RESULTS: Both HMGB1 and B box increased the permeability of
      Caco-2 monolayers to fluorescein isothiocyanate-labeled dextran (FD4) in a time-
      and dose-dependent fashion. The increase in permeability was reversible following
      removal of the recombinant protein. Exposure of Caco-2 cells to B box resulted in
      increased expression of inducible nitric oxide synthase messenger RNA and
      increased production of NO. When we used various pharmacologic strategies to
      inhibit NO production or scavenge NO or peroxynitrite (ONOO(-)), we abrogated B
      box-induced hyperpermeability. Administration of B box to wild-type mice
      increased both ileal mucosal permeability to FD4 and bacterial translocation to
      mesenteric lymph nodes. These effects were not observed in inducible nitric oxide
      synthase knockout mice. CONCLUSIONS: These data support the view that HMGB1 and B
      box are capable of causing alterations in gut barrier function via a mechanism
      that depends on the formation of NO and ONOO(-).

PMID- 12198706
TI  - Celiac lesion T cells recognize epitopes that cluster in regions of gliadins rich
      in proline residues.
AB  - BACKGROUND & AIMS: Celiac disease is a gluten-induced enteropathy that shows a
      strong association with HLA-DQ2 and -DQ8. Gluten-specific T cells, invariably
      restricted by DQ2 or DQ8, can be isolated from celiac lesions. Such gut-derived T
      cells have a preference for recognition of gluten that has been specifically
      deamidated by tissue transglutaminase. Only a few gliadin T-cell epitopes have
      been identified by earlier work. The aim of this study was to perform a
      systematic characterization of DQ2-restricted T-cell epitopes in alpha- and gamma
      gliadins. METHODS: Epitopes were identified by mass spectrometry analysis of
      peptide fragments of recombinant gliadins and by use of synthetic peptides.
      RESULTS: We identified several new gamma-gliadin epitopes and an additional alpha
      gliadin epitope. Interestingly, these and the previously identified epitopes are
      not randomly scattered across the gliadins but cluster in regions of the proteins
      with high content of proline residues. CONCLUSIONS: Several DQ2-restricted T-cell
      epitopes exist in gliadin that are located in regions rich in proline. This
      likely reflects epitope selection at the levels of digestive and antigen
      presenting cell processing, transglutaminase-mediated deamidation, and/or peptide
      binding to DQ2.

PMID- 12198707
TI  - The type of sodium-coupled solute modulates small bowel mucosal injury, transport
      function, and ATP after ischemia/reperfusion injury in rats.
AB  - BACKGROUND & AIMS: Gastrointestinal function may be impaired after severe injury,
      hampering tolerance to enteral nutrition. The purpose of this study was to
      determine how different sodium-coupled solutes modulate gut function after
      ischemia/reperfusion (I/R) in a rodent model. METHODS: At laparotomy, rats had
      jejunal sacs filled with (glucose + alanine), glucose, glutamine, alanine, or
      mannitol (osmotic control), followed by superior mesenteric artery clamping for
      60 minutes and 30 minutes of reperfusion. After reperfusion, sacs were harvested
      for morphologic examination, adenosine triphosphate (ATP) assay, or mounted in an
      Ussing chamber. RESULTS: Small intestinal epithelial absorptive capacity, as
      assessed by changes in short-circuit current in response to glucose, after gut
      I/R, was decreased by alanine or (glucose + alanine) but not glucose or glutamine
      alone and correlated with changes in tissue ATP. Gut I/R caused a significant
      morphologic injury that was worsened by alanine or (glucose + alanine) but
      lessened by glucose or glutamine alone. CONCLUSIONS: During gut I/R, alanine can
      enhance gut injury, deplete energy (ATP), and impair gut absorption, whereas
      glucose or glutamine is protective against injury and can maintain absorptive
      capacity and ATP. These results suggest that solutes (such as alanine), which
      further stress an already metabolically stressed bowel, should be cautiously
      administered to critically ill patients whereas those solutes that contribute to
      energy production (such as glucose and glutamine) may be safely continued.

PMID- 12198708
TI  - Expression of human intestinal mucin is modulated by the beta-galactoside binding
      protein galectin-3 in colon cancer.
AB  - BACKGROUND & AIMS: Alterations in the production of the beta-galactoside binding
      protein galectin-3 and of MUC2 intestinal mucin have been independently
      correlated with the malignant behavior of human colon cancer cells. MUC2 mucin is
      a major ligand for galectin-3, and colon cancer cells that differ quantitatively
      in MUC2 expression may also vary in expression of galectin-3. The current study
      was designed to investigate the relationship between galectin-3 production and
      MUC2 mucin synthesis by human colon cancer cells. METHODS: The effect of galectin
      3 on MUC2 mucin production was assessed by stable transfection of sense and
      antisense galectin-3 expression constructs under the control of constitutive or
      tetracycline-inducible promoters into human colon cancer cells. Galectin-3 and
      MUC2 expression were determined by fluorescence-activated cell sorter (cell
      surface galectin-3), Western and Northern analysis (galectin-3, MUC2), and gel
      filtration of secreted high-weight glycoprotein (MUC2). In vitro results were
      confirmed in vivo by analysis of cecal xenografts in athymic mice. RESULTS: Colon
      cancer cells with high levels of galectin-3 also had high levels of MUC2 mucin,
      whereas those with low galectin-3 levels had low MUC2 levels. Alterations in
      galectin-3 levels by expression of sense or antisense galectin-3 constructs
      resulted in parallel alterations of MUC2 protein and RNA. Induction of antisense
      to galectin-3 in vivo was associated with decreases in both galectin-3 and MUC2
      protein in cecal xenografts. CONCLUSIONS: The beta-galactoside binding protein
      galectin-3 modulates the expression of its major ligand MUC2 mucin in human colon
      cancer cells. This may have important implications for understanding the role of
      galectin-3 in colon cancer metastasis.

PMID- 12198709
TI  - Coupling of M2 muscarinic receptor to L-type Ca channel via c-src kinase in
      rabbit colonic circular smooth muscle.
AB  - BACKGROUND & AIMS: The L-type Ca(2+) channel is a major pathway for Ca(2+) influx
      in colonic smooth muscle and is modulated by endogenous levels of nonreceptor
      tyrosine kinase, c-src. Tyrosine kinases are also activated by G-protein-coupled
      receptors (GPCR). This study determined whether muscarinic receptor couples to
      Ca(2+) channels via c-src kinase. METHODS: Currents were measured in rabbit
      colonic smooth muscle cells and in transfected HEK293 cells by patch-clamp
      technique. Tyrosyl phosphorylated proteins were detected by Western blots and the
      interaction of c-src with the c-terminus of alpha subunit of Ca(2+) channel was
      determined by a GST pull-down assay. RESULTS: Methacholine (10 micromol/L)
      enhanced Ca(2+) channel currents by 30% under conditions whereby the M(3)
      receptor pathway was blocked by either 4-DAMP or by intracellular dialysis with
      anti-Galphaq antibody. Similar effects were observed by blocking intracellular
      Ca(2+) release with heparin. Enhancement was abolished by intracellular anti
      Galphai antibody and by the c-src inhibitor, PP2 but unaffected by the inactive
      analog PP3. Immunoblot with anti-src antibody revealed increased src
      phosphorylation by muscarinic receptor stimulation. Purified c-src directly
      associated with the c-terminus of alpha1c subunit of the Ca(2+) channel. In M(2)
      receptor transfected HEK293 cells, currents were enhanced 2-fold by carbachol.
      CONCLUSIONS: These studies demonstrate stimulation of Ca(2+) current in colonic
      smooth muscle cells by M2 receptor coupled to Galphai-G protein and c-src
      activation. They also suggest a central role of c-src kinase in the cross-talk
      between tyrosine kinase receptor and GPCR.

PMID- 12198710
TI  - Hepcidin expression inversely correlates with the expression of duodenal iron
      transporters and iron absorption in rats.
AB  - BACKGROUND & AIMS: Hepcidin is an antimicrobial peptide thought to be involved in
      the regulation of intestinal iron absorption. To further investigate its role in
      this process, we examined hepatic and duodenal gene expression in rats after the
      switch from a control diet to an iron-deficient diet. METHODS: Adult rats on an
      iron-replete diet were switched to an iron-deficient diet and the expression of
      iron homeostasis molecules in duodenal and liver tissue was studied over 14 days.
      Intestinal iron absorption was determined at these same time-points by measuring
      the retention of an oral dose of (59)Fe. RESULTS: Iron absorption increased 2.7
      fold within 6 days of switching to an iron-deficient diet and was accompanied by
      an increase in the duodenal expression of Dcytb, divalent metal transporter 1,
      and Ireg1. These changes precisely correlated with decreases in hepatic hepcidin
      expression and transferrin saturation. No change in iron stores or hematologic
      parameters was detected. CONCLUSIONS: This study showed a close relationship
      between the expression of hepcidin, duodenal iron transporters, and iron
      absorption. Both hepcidin expression and iron absorption can be regulated before
      iron stores and erythropoiesis are affected, and transferrin saturation may
      signal such changes.

PMID- 12198712
TI  - Emerging concepts in colorectal neoplasia.
AB  - An understanding of the mechanisms that explain the initiation and early
      evolution of colorectal cancer should facilitate the development of new
      approaches to effective prevention and intervention. This review highlights
      deficiencies in the current model for colorectal neoplasia in which APC mutation
      is placed at the point of initiation. Other genes implicated in the regulation of
      apoptosis and DNA repair may underlie the early development of colorectal cancer.
      Inactivation of these genes may occur not by mutation or loss but through
      silencing mediated by methylation of the gene's promoter region. hMLH1 and MGMT
      are examples of DNA repair genes that are silenced by methylation. Loss of
      expression of hMLH1 and MGMT protein has been demonstrated immunohistochemically
      in serrated polyps. Multiple lines of evidence point to a "serrated" pathway of
      neoplasia that is driven by inhibition of apoptosis and the subsequent
      inactivation of DNA repair genes by promoter methylation. The earliest lesions in
      this pathway are aberrant crypt foci (ACF). These may develop into hyperplastic
      polyps or transform while still of microscopic size into admixed polyps, serrated
      adenomas, or traditional adenomas. Cancers developing from these lesions may show
      high- or low-level microsatellite instability (MSI-H and MSI-L, respectively) or
      may be microsatellite stable (MSS). The suggested clinical model for this
      alternative pathway is the condition hyperplastic polyposis. If colorectal cancer
      is a heterogeneous disease comprising discrete subsets that evolve through
      different pathways, it is evident that these subsets will need to be studied
      individually in the future.

PMID- 12198711
TI  - Caspase 9-dependent killing of hepatic stellate cells by activated Kupffer cells.
AB  - BACKGROUND & AIMS: Hepatic stellate cells play an important role in liver
      fibrogenesis, and hepatic stellate cell death may be involved in the termination
      of this response. METHODS: Molecular mechanisms of hepatic stellate cell killing
      were studied in hepatic stellate cell/Kupffer cell cocultures. RESULTS:
      Lipopolysaccharide stimulation of hepatic stellate cell/Kupffer cell cocultures,
      but not of hepatic stellate cell monocultures, induced profound alterations of
      hepatic stellate cell morphology and hepatic stellate cell death. Kupffer cell
      induced hepatic stellate cell killing required hepatic stellate cell/Kupffer cell
      contacts and was prevented by dexamethasone, prostaglandin E(2), tumor necrosis
      factor-related apoptosis-inducing ligand (TRAIL) receptor 2 antagonists, and down
      regulation of receptor-interacting protein, but not by antioxidants, tumor
      necrosis factor receptor, or CD95 antagonists. Hepatic stellate cell death was
      characterized by activation of caspases 3, 8, and 9, terminal deoxynucleotidyl
      transferase-mediated deoxyuridine triphosphate nick-end labeling negativity, lack
      of gross calcium overload, and TRAIL trafficking to the plasma membrane.
      Inhibition of caspase 9, but not of caspases 3, 8, or 10, prevented hepatic
      stellate cell death. Lipopolysaccharide induced a dexamethasone- and
      prostaglandin E(2)-sensitive expression of TRAIL in Kupffer cells. TRAIL
      receptors 1 and 2, FLIP (caspase 8-inhibitory protein), and receptor-interacting
      protein were up-regulated during hepatic stellate cell transformation; however,
      TRAIL addition did not induce hepatic stellate cell death. Hepatic stellate cell
      susceptibility toward Kupffer cell-induced death paralleled receptor-interacting
      protein and TRAIL-receptor expression levels. CONCLUSIONS: Activated Kupffer cell
      can effectively kill hepatic stellate cell by a caspase 9- and receptor
      interacting protein-dependent mechanism, possibly involving TRAIL. The data may
      suggest a novel form of hepatic stellate cell death.

PMID- 12198713
TI  - Joint statement on missions and submissions of papers to AGA journals.

PMID- 12198714
TI  - American Gastroenterological Association medical position statement on Obesity.

PMID- 12198715
TI  - AGA technical review on obesity.

PMID- 12198716
TI  - Much to do about gas.

PMID- 12198717
TI  - APC as a checkpoint gene: the beginning or the end?

PMID- 12198718
TI  - Celiac disease pathogenesis: the plot thickens.

PMID- 12198719
TI  - And now...fattening the lower esophageal sphincter.

PMID- 12198720
TI  - More than food trafficks into the esophagus.

PMID- 12198721
TI  - Viral discrimination and subversion of host defense at the epithelial gateway.

PMID- 12198726
TI  - Celiac disease-like abnormalities in IBS: wrong title or wrong disease?

PMID- 12198722
TI  - In search of vulcan: Where are all the iron men (and women)?

PMID- 12198728
TI  - Gastric surgery and Barrett's esophagus.

PMID- 12198729
TI  - Discussion on preoperative prevalence of Barrett's esophagus in esophageal
      adenocarcinoma: a systemic review.

PMID- 12198731
TI  - Mucosal flora in inflammatory bowel disease: Intraepithelial bacteria or
      endocrine epithelial cell secretory granules?

PMID- 12198733
TI  - "High-grade MALT" vs. diffuse large B cell lymphoma.

PMID- 12198736
TI  - Love and sexuality in aging.

PMID- 12198737
TI  - The Aging Male.

PMID- 12198738
TI  - Investigation, treatment and monitoring of late-onset hypogonadism in males.
      Official recommendations of ISSAM. International Society for the Study of the
      Aging Male.

PMID- 12198739
TI  - Health-related quality of life in old age: preliminary report on the male
      perspective.
AB  - Health-related quality of life is a key element of successful aging. With life
      expectancy increasing, postmenopausal estrogen/gestagen replacement therapy has
      been under discussion for some time with the aim of achieving a higher quality of
      life in old age. For a long time, the relevance of hormonal aging was only
      discussed with reference to women; however, more recent work deals with concepts
      that affect both sexes. According to recent studies, numerous symptoms and
      complaints which may impair quality of life, can be attributed to hormonal
      changes in old age in both women and men. The majority of age-related complaints,
      such as a decline in physical performance, decreased sexual activity and a
      deterioration of general well-being, are strongly reminiscent of the symptoms of
      classical pituitary disorders in adulthood. Since the early 1990s, scientific
      studies have also been investigating the influence of hormone 'replacement' in
      elderly men, using, for example, growth hormones. However, until now there has
      been no suitable measure for assessing the quality of life specifically in
      elderly men. In a research project aimed at developing a questionnaire (the VITA
      questionnaire), roughly equal numbers of elderly men and women were asked about
      their subjective health and quality of life. It was found that men assessed their
      health-related quality of life very positively in a number of different
      dimensions of the questionnaire. In the present article the individual aspects of
      the quality of life of men are described and examples of gender-related
      differences are presented and discussed.

PMID- 12198740
TI  - Estradiol in elderly men.
AB  - The role of estrogens in male physiology has become more evident, as a
      consequence of the discovery of human models of estrogen deficiency such as
      estrogen resistance or aromatase deficiency. In males, testosterone is the major
      source of plasma estradiol, the main biologically active estrogen, only 20% of
      which is secreted by the testes. Plasma estrone, 5% of which is converted to
      plasma estradiol, originates from tissue aromatization of, mainly adrenal,
      androstenedione. The plasma concentration of estradiol in males is 2-3 ng/dl and
      its production rate in blood is 25-40 micrograms/24 h; both of these values are
      significantly higher than in postmenopausal women. Plasma levels of estradiol do
      not necessarily reflect tissue-level activity as peripherally formed estradiol is
      partially metabolized in situ; thus, not all enters the general circulation, with
      a fraction remaining only locally active. Of the factors influencing plasma
      estradiol levels, plasma testosterone is a major determinant. However, the age
      associated decrease in testosterone levels is scarcely reflected in plasma
      estradiol levels, as a result of increasing aromatase activity with age and the
      age-associated increase in fat mass. Free and bioavailable estradiol levels do
      decrease modestly with age as does the ratio of free testosterone to free
      estradiol, the latter testifying to the age-associated increased aromatization of
      testosterone. Estradiol levels are highly significantly positively related to
      body fat mass and more specifically to subcutaneous abdominal fat, but not to
      visceral (omental) fat. Indeed, aromatase activity in omental fat is only one
      tenth of the activity in gluteal fat. Estrogens in males play an important role
      in the regulation of the gonadotropin feedback, several brain functions, bone
      maturation, regulation of bone resorption and in lipid metabolism. Moreover, they
      affect skin metabolism and are an important factor determining sex interest in
      man.

PMID- 12198741
TI  - What's new on the dental scene? Browsing through the dental literature.

PMID- 12198742
TI  - Anterior crowding--just an esthetic problem?
AB  - BACKGROUND: One frequent late sequel of frontal crowding is the development of
      gingival recessions manifesting themselves especially at rotated anterior teeth.
      MATERIAL: This correlation is discussed with regard to the literature and to the
      authors' own clinical findings and experimental studies. RESULTS: According to
      present-day knowledge the following statements can be made: In cases with frontal
      crowding the tangential stiffening of the anterior teeth is inadequate. Thus
      translatory and rotational force components resulting from the elastic
      deformation of the mandible under functional loading effect the movement of
      rotated front teeth during maximum jaw opening and mandibular protrusion. Also
      tongue thrusting and frontolateral bruxism lead to force vectors in vestibular
      direction affecting the delicate periodontal tissues. These statements are
      confirmed by the authors' own in-vivo experimental studies measuring the amount
      of tooth displacement during test persons' functional movements. Furthermore, in
      the long-term anterior crowding will mostly trigger incorrect anterior guidance,
      i.e. guidance predominantly by the rotated or ectopically positioned front tooth
      with subsequent overloading of the antagonist. CONCLUSION: Orthodontic therapy of
      frontal crowding is not just an esthetic problem but can be of special importance
      in the prevention of stress-related reactions in the masticatory system.

PMID- 12198743
TI  - Curvature morphology of the mandibular dentition and the development of concave
      convex vertical stripping instruments.
AB  - Radii for concave-convex vertical stripping instruments can be derived from
      measurements of the natural curvature morphology in the horizontal contact area
      of the mandibular dentition. The concave-convex adjustment of contacts in the
      anterior dental arch with a newly developed set of concave-convex stripping
      instruments should enable orthodontic crowding problems to be alleviated
      biomechanically.

PMID- 12198744
TI  - Study of the extent of torque, protrusion and intrusion of the incisors in the
      context of Class II, division 2 treatment in adults.
AB  - AIM: The aim of this study was to analyze the relative contribution of torque and
      protrusion to the change in incisor inclination in the treatment of Class II,
      Division 2 malocclusion with fixed appliances. Furthermore, the extent of incisor
      intrusion was to be evaluated. The second part of the study was aimed at
      documenting the stability of the therapeutic outcome in terms of inclination and
      intrusion within the framework of a follow-up examination. PATIENTS AND METHOD:
      The study sample comprised 25 adult patients, and the follow-up sample eleven
      patients. The intrusion and change in inclination of the incisors as well as
      their stability were analyzed by evaluating and superimposing lateral
      cephalograms taken before and after treatment as well as after retention.
      RESULTS: Although the mean value of inclination at the end of the therapy was in
      accordance with the standard value (102 degrees), there was a marked
      interindividual variation. In the maxilla, the mean torque component was 58%, and
      the mean protrusion component 42%. In the mandible, the torque: protrusion ratio
      was 37%:63%. The mean intrusion was 1 mm in both dental arches. The follow-up
      examination showed that the intrusion was relatively stable. In cases where the
      change in inclination relapsed, the ratio of protrusion to torque was almost
      equal to that previously used to induce the change during the course of
      treatment. CONCLUSION: It is concluded that therapy with torque movement and
      intrusion offers a more stable result in adults than protrusion movement alone.

PMID- 12198745
TI  - Dental arches and occlusion in bilateral cleft lip and palate patients after two
      different routines for palatal surgery.
AB  - BACKGROUND: Delayed hard palate repair (DHPR) is believed by many researchers to
      improve maxillary growth and facial appearance in patients born with cleft lip
      and palate. However, only few studies dealing with the midfacial growth outcome
      after this type of surgery in bilateral cleft patients have been published.
      PATIENTS AND METHOD: The purpose of this retrospective study was to compare long
      term results of maxillary morphology, dental arches and occlusion in two groups
      of patients with bilateral cleft lip and palate. The palatal surgery differed
      between the two groups, particularly with respect to the timing of hard palate
      repair. The DHPR group (n = 16) underwent soft palate closure at 12 months and
      hard palate repair at around 8 years, whereas the early palatal repair group
      (EPR) (n = 12) had completed two-stage palatal closure during the first year of
      life. These latter subjects had undergone more traditional palatal surgery with
      vomer flaps for repair of the anterior part and push-back closure for the
      posterior part of the cleft. Surgery was performed in both groups by the same
      surgical team at Sahlgrenska University Hospital, Goteborg, Sweden. Dental casts
      were used to analyze the pre- and postoperative maxillary morphology, dental arch
      dimensions, and occlusion of both samples, which were followed longitudinally
      from infancy to early adulthood. RESULTS: Differences recorded in both maxillary
      growth and occlusion were generally in favor of the DHPR group. However, major
      intragroup variations and relatively small sample sizes precluded statistical
      verification of the differences, except for development during the early stages.

PMID- 12198746
TI  - Cephalometric analysis in patients with obstructive sleep apnea. Part II:
      Prognostic value in treatment with a mandibular advancement device.
AB  - BACKGROUND: The mandibular advancement device (MAD) is accepted as an additional
      treatment option for snoring and mild obstructive sleep disorders. Its
      therapeutic efficacy can only be verified through nocturnal polysomnography with
      the appliance in situ. The relevance of the craniofacial skeletal and soft-tissue
      structures as an etiological cofactor is controversial. While the lateral
      cephalogram of the facial skeleton is of no direct diagnostic relevance, it
      remains unclear to what extent cephalometric assessment can provide prognostic
      information to better ensure treatment success with an MAD. METHODS AND RESULTS:
      This study is based on the evaluation of 57 patients diagnosed
      polysomnographically with obstructive sleep apnea (OSA). The patients were
      treated primarily with a modified activator; after 6-12 weeks, control
      polysomnography was carried out in the sleep laboratory. The cephalometric
      variables were analyzed using a multivariate regression procedure with the
      response variable of treatment outcome. In addition to a horizontal craniofacial
      morphology, the downward and forward posture of the hyoid is a prognostic
      variable for effective therapy with an MAD.

PMID- 12198747
TI  - Orthodontic soldering techniques: aspects of quality assurance in the dental
      laboratory.
AB  - BACKGROUND: In Germany, the dental technician is required by the Medical Products
      Act (MPG) to produce workpieces of high safety and quality and to document these
      properties. Soldering continues to be the prevailing joining technique in the
      dental laboratory, although problems arise from the susceptibility to corrosion
      and the low strength of soldered joints. This study aimed to reveal sources of
      defects in dental laboratory workpieces in order to achieve optimization in terms
      of quality assurance. MATERIAL AND METHODS: The joints were produced by various
      dental technicians using three different soldering techniques. These joining
      techniques were investigated for their quality and their corrosion properties
      during immersion in ferric chloride, orthodontic appliance cleanser, and
      artificial saliva. Observance of the soldering instructions by the dental
      technicians was checked. Corrosion attack was confirmed by scanning electron
      microscopy and by measuring the ion concentrations of copper, silver and zinc in
      the corrosive agents, using atomic emission spectroscopy with stimulation by
      inductively coupled plasma (ICP-AES analysis). RESULTS AND DISCUSSION: Incomplete
      filling of the soldering gap, porosities resulting from the production process,
      poor corrosion properties, and in particular a high variability of the measured
      values point to insufficient reliability of two soldering techniques. Variations
      in quality were also detected among the technicians' modes of operation.
      CONCLUSION: The analyses confirm the need for quality assurance of soldering
      techniques and for increased support for alternative joining techniques such as
      laser welding in the future. The results of the studies on laser welding are
      presented in a separate publication.

PMID- 12198748
TI  - Bilateral open bite in dicygotic twins. A combined orthodontic-prosthetic
      approach.
AB  - CASE REPORT: Dizygotic twins, male, 25 years of age, required treatment for an
      identical orthodontic diagnosis. DIAGNOSIS: Class III malocclusion with mesial
      molar relation and frontal edge-to-edge bite, lyrate upper dental arch, grouped
      cross-bite and bilateral open bite in the molar and bicuspid region, retention
      and lingual inclination respectively of the lower left second bicuspid, mesial
      inclination of both lower first molars. The severity of the malocclusion differed
      in the two brothers. THERAPY: Orthodontic treatment was successful concerning the
      transversal expansion and alignment of the maxillary dental arch, the functional
      relation of the anterior teeth, the transversally correct relation of the upper
      and lower dental arches and, following surgical removal of the lower second
      bicuspids, the reduction of crowding in the lower arch. An attempt was made to
      upright the molars in the mandibular arch and to close the lateral open bite by
      means of vertical elastics. However, the 10-month period of resistance to the
      therapy suggested, after a tongue protrusion habit had been ruled out, a
      diagnosis of ankylosis. Further orthodontic treatment was renounced and a
      prosthetic solution was pursued instead: the teeth in infraocclusion were treated
      with full ceramic overlays and, in the regions with residual gaps, with pontics
      (Empress II, Ivoclar, Schaan, Liechtenstein), after minimally invasive
      preparation (confined to removal of existing fillings). CONCLUSION: This case is
      particularly interesting because the infrapositioned molars in both brothers were
      very likely due to ankylosis, suggesting a genetic cause.

PMID- 12198749
TI  - When wheezing may not mean asthma. Other common and uncommon causes to consider.
AB  - Establishing that wheezing is not due to asthma requires attention to the
      patient's history, physical examination results, and response to therapy. If the
      diagnosis of asthma is questionable, appropriate pulmonary function tests should
      be performed to firmly establish or refute that the wheezing is due to asthma. If
      asthma is not the cause, other entities need to be considered so that
      inappropriate therapy is not prescribed.

PMID- 12198750
TI  - Patient notes: antibiotic resistance.

PMID- 12198751
TI  - The new cholesterol guidelines. Applying them in clinical practice.
AB  - In 2001, the National Institutes of Health released the third report of the
      National Cholesterol Education Program (NCEP) Expert Panel on Detection,
      Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment
      Panel III). Compared with previous cholesterol guidelines, the new guidelines
      contain several significant changes in treatment recommendations for patients
      with hyperlipidemia. In this article, Dr Pearlman reviews the latest guidelines
      and offers case examples that demonstrate how to incorporate the recommendations
      routinely into clinical practice.

PMID- 12198752
TI  - Understanding the Mediterranean diet. Could this be the new "gold standard" for
      heart disease prevention?
AB  - The traditional Mediterranean diet as outlined in this article is an ideal eating
      pattern for prevention of cardiovascular disease. The essence of this diet is the
      use of natural, whole foods and the avoidance of highly processed ones. We
      believe that current understanding and scientific evidence are adequate to
      recommend this diet widely as a practical, effective, and enjoyable strategy--the
      new "gold standard"--in heart disease prevention.

PMID- 12198753
TI  - Raising the bar in research ethics.

PMID- 12198754
TI  - Bacteria as agents of biowarfare. How to proceed when the worst is suspected.
AB  - Recognition of an increasing incidence of uncommon pneumonias with a high
      mortality rate, clusters of cases, or a high incidence of pet illnesses or death
      should alert medical personnel to the possibility of terrorism with bacteriologic
      agents. Prompt reporting of such unusual occurrences to the local health
      department is of paramount importance for early identification of cases,
      treatment initiation, and institution of preventive measures.

PMID- 12198755
TI  - Defending against viruses in biowarfare. How to respond to smallpox,
      encephalitides, hemorrhagic fevers.
AB  - The threat of bioterrorism with use of viruses is increasing. Smallpox,
      encephalitis, and hemorrhagic fevers are the most likely diseases to result from
      viral deployment. It is critical that all healthcare professionals become
      familiar with the clinical presentation, diagnosis, management, and prevention of
      these diseases. Awareness and preparedness are instrumental in reducing viral
      transmission and improving survival of the victims.

PMID- 12198756
TI  - When biotoxins are tools of terror. Early recognition of intentional poisoning
      can attenuate effects.
AB  - Toxin-mediated diseases have made humans ill for millennia. They also have been
      used in beneficial ways. Unfortunately, the use of biological agents as weapons
      of terror has now been realized, and separating naturally occurring disease from
      bioterroristic events has become an important public health goal. The key to
      timely identification of such attacks relies on education of primary care
      physicians, first responders, and public health officials. We must remain
      vigilant to unusual case presentations or clusters of similar cases and report
      them immediately to public health authorities.

PMID- 12198757
TI  - Image understanding methods in biomedical informatics and digital imaging.
AB  - This paper will present new possibilities for the application of image
      recognition methods and AI application in biomedical informatics as well as
      semantically oriented analysis of 2D images of coronary arteries originating from
      coronography examinations. In particular this paper presents the possibilities
      for computer analysis and recognition of local stenoses of the lumen of coronary
      arteries via the application of syntactic methods of pattern recognition. Such
      stenoses are the result of the appearance of arteriosclerosis plaques, which in
      consequence lead to different forms of ischemic cardiovascular diseases. Such
      diseases may be seen in the form of stable or unstable disturbances of heart
      rhythm or infarction. Analysis of the correct morphology of these artery lumina
      is made possible with the application of syntactic analysis and pattern
      recognition methods, in particular with the attribute, context-free grammar of
      look-ahead LR(1) type.

PMID- 12198758
TI  - Methodology used for "software for automated linkage in Italy" (SALI).
AB  - Linkage of epidemiological registries can provide cost-effective information on
      the associations between different diseases or exposures in the population under
      study and on completeness of surveillance system databases. We describe the
      program SALI (software for automated linkage in Italy) aimed at matching
      individual records from medium-sized registries (in the order of 100,000
      records), where the desired outcome is to miss as few links as possible and,
      because of low link-likelihood (< 1%), a manual revision of matched pairs is
      feasible. SALI, developed in CA-Clipper language, uses registry files in dBase
      format. It requires only name, surname, and date of birth as key fields, and it
      allows for spelling errors in Italian or other Latin languages through a specific
      algorithm. Furthermore, a double-blind procedure ensures data confidentiality.
      The main linkage procedure is based on four stages, two automatic ones, and two
      where the operator can decide through specific windows whether to accept stage
      selected matches. SALI takes into account possible errors in key fields thus
      reducing false negatives. It was used to solve the problem of linkage between
      AIDS and cancer registries in Italy. It can be used with every IBM-compatible
      computer system, assuring uniquely high portability.

PMID- 12198759
TI  - Comparing the similarity of time-series gene expression using signal processing
      metrics.
AB  - Many algorithms have been used to cluster genes measured by microarray across a
      time series. Instead of clustering, our goal was to compare all pairs of genes to
      determine whether there was evidence of a phase shift between them. We describe a
      technique where gene expression is treated as a discrete time-invariant signal,
      allowing the use of digital signal-processing tools, including power spectral
      density, coherence, and transfer gain and phase shift. We used these on a public
      RNA expression set of 2467 genes measured every 7 min for 119 min and found 18
      putative associations. Two of these were known in the biomedical literature and
      may have been missed using correlation coefficients. Digital signal processing
      tools can be embedded and enhance existing clustering algorithms.

PMID- 12198760
TI  - High-performance implementation and analysis of the Linkmap program.
AB  - Linkage analysis uses information from family pedigrees to map genes and locate
      disease genes on particular chromosomes. A recombination fraction denoted as
      theta is estimated as a measure of crossing over between two loci. Genetic
      linkage calculations are very time-consuming particularly for large family
      pedigrees, a large number of theta values, and an increased number of markers.
      This paper reports the implementation of a dynamic master-slave scheme for the
      parallelization of the Linkmap program on a high-performance cluster such as the
      Origin 2000 (O2K) consisting of 56 R12000 processors. The Linkmap program is one
      of four programs in the LINKAGE/FASTLINK legacy package widely used by the
      medical research community. Implementations issues are addressed and results are
      compared with previous results on a cluster of DEC Alphas, and with the
      sequential execution on the O2K machine.

PMID- 12198761
TI  - Representing patient preference-related concepts for inclusion in electronic
      health records.
AB  - In recent years shared decision making between patients and their health care
      providers and the inclusion of patient preferences in patient care have been, in
      theory, embraced as models for good clinical practice. Patients' experiences,
      values, and preferences are increasingly acknowledged as important pieces of
      evidence for appropriate health care decision making. To effectively use
      information about patient preferences in patient care, this information, which is
      gathered through a process of preference elicitation, needs to be integrated with
      other types of information, e.g., diagnoses, treatments, and patient status
      indicators within the context of a longitudinal electronic health record. This
      integration requires that patient preference-related concepts be represented
      nonambiguously and in a manner that renders them suitable for computer rather
      than human processing. In this article, the authors describe important patient
      preference-related concepts and illustrate the use of the LOINC semantic
      structure as a terminology model to create fully specified names for a sample of
      15 preference elicitations from 8 published research articles.

PMID- 12198762
TI  - Medical informatics and bioinformatics: European efforts to facilitate synergy.
AB  - Over the past decade there have been several attempts to rethink the basic
      strategies and scope of medical informatics. Meanwhile, bioinformatics has only
      recently experienced a similar debate about its scientific character. Both
      disciplines envision the development of novel diagnostic, therapeutic, and
      management tools, and products for patient care. A combination of the expertise
      of medical informatics in developing clinical applications and the focused
      principles that have guided bioinformatics could create a synergy between the two
      areas of application. Such interaction could have a great influence on future
      health research and the ultimate goal, namely continuity and individualization of
      health care. This article summarizes current activities related to facilitating
      synergy between medical informatics and bioinformatics, emphasizing activities in
      Europe while relating them to efforts in other parts of the world. The report
      provides examples of the analysis that European investigators are carrying out,
      aiming to propose new ideas for collaborations between medical informatics and
      bioinformatics researchers in a variety of areas.

PMID- 12198763
TI  - Modeling medical prognosis: survival analysis techniques.
AB  - Medical prognosis has played an increasing role in health care. Reliable
      prognostic models that are based on survival analysis techniques have been
      recently applied to a variety of domains, with varying degrees of success. In
      this article, we review some methods commonly used to model time-oriented data,
      such as Kaplan-Meier curves, Cox proportional hazards, and logistic regression,
      and discuss their applications in medical prognosis. Nonlinear, nonparametric
      models such as neural networks have increasingly been used for building
      prognostic models. We review their use in several medical domains and discuss
      different implementation strategies. Advantages and disadvantages of these
      methods are outlined, as well as pointers to pertinent literature.

PMID- 12198764
TI  - B16F10 melanoma cell colonization of mouse lung is enhanced by partial
      pneumonectomy.
AB  - Surgical resection of lung tissue is employed clinically as a therapy for
      pulmonary metastases; however, local cancer recurrence is a frequent post
      surgical complication. In a variety of small mammals, left pneumonectomy (PNX)
      initiates rapid compensatory hyperplasia of the remnant lung lobes restoring
      normal tissue mass, structure and function. Post-PNX compensatory lung growth is
      known to promote lung tumor formation in carcinogen-treated mice. The present
      study tests the hypothesis that PNX enhances experimental metastasis to lung.
      C57B1/6 mice subjected to PNX were given an intravenous injection of B16F10
      melanoma cells at various stages of compensatory lung growth. Animals injected
      with B16F10 cells during the linear phase of the response had 77% to 260% more
      pulmonary metastases than mice subjected to thoracotomy (P < 0.01). Moreover,
      measurements of tumor area (mm2) revealed that PNX mice harbored a substantially
      larger lung tumor burden than control animals. Normalization of the tumor cell
      inoculum to lung mass yielded similar results. PNX had no effect on growth of sub
      cutaneous B16F10 melanoma tumors, suggesting that experimental melanoma
      metastasis was enhanced by local alterations in the lung microenvironment. These
      results suggest (1) that PNX is a relevant model in which to investigate
      mechanisms of local cancer recurrence and, (2) melanoma cell metastatic potential
      is influenced, at least in part, by local factors modified during post-PNX
      compensatory lung growth.

PMID- 12198766
TI  - Protein expression profile of primary human squamous cell lung carcinomas
      indicative of the incidence of metastases.
AB  - The purpose of this investigation was to evaluate firstly whether different
      protein expression patterns exist in primary squamous cell lung carcinomas of
      patients with and without lymph node involvement and secondly, whether or not
      different patterns exist in tumours with positive lymph nodes. For this reason,
      formalin-fixed, paraffin-embedded specimens from 130 patients with squamous cell
      lung carcinomas were analyzed by immunohistochemistry. In a first step, proteins
      were selected which showed a relationship to lymph node involvement. The
      expression of JUN, ERBB2, MYC, cyclin D, PCNA, bFGF, VEGF and Hsp70 proteins
      revealed a positive correlation to lymph node involvement. In contrast, caspase
      3, Fas ligand, Fas/CD95, and PAI showed an inverse correlation to lymph node
      involvement. In a second step, these parameters were further analyzed by
      hierarchical cluster analyses. The resulting clusters were correlated to patients
      with or without lymph node involvement. The data show that different protein
      expression patterns exist between primary squamous cell lung carcinomas with and
      without lymph node involvement and within carcinomas with lymph node involvement.
      The data suggest that various metastasis profiles exist.

PMID- 12198765
TI  - Correlation between extent of osteolytic damage and metastatic burden of human
      breast cancer metastasis in nude mice: real-time PCR quantitation.
AB  - Orthotopic or intracardiac injection of human breast cancer cell lines into
      immunocompromised mice allows study of the molecular basis of breast cancer
      metastasis. We have established a quantitative real-time PCR approach to analyze
      metastatic spread of human breast cancer cells inoculated into nude mice via
      these routes. We employed MDA-MB-231 human breast cancer cells genetically tagged
      with a bacterial beta-galactosidase (Lac-Z) retroviral vector, enabling their
      detection by TaqMan real-time PCR. PCR detection was linear, specific, more
      sensitive than conventional PCR, and could be used to directly quantitative
      metastatic burden in bone and soft organs. Attesting to the sensitivity and
      specificity of the PCR detection strategy, as few as several hundred metastatic
      MDA-MB-231 cells were detectable in 100 microns segments of paraffin-embedded
      lung tissue, and only in samples adjacent to sections that scored positive by
      histological detection. Moreover, the measured real-time PCR metastatic burden in
      the bone environment (mouse hind-limbs, n = 48) displayed a high correlation to
      the degree of osteolytic damage observed by high resolution X-ray analysis (r2 =
      0.972). Such a direct linear relationship to tumor burden and bone damage
      substantiates the so-called 'vicious cycle' hypothesis in which metastatic tumor
      cells promote the release of factors from the bone which continue to stimulate
      the tumor cells. The technique provides a useful tool for molecular and cellular
      analysis of human breast cancer metastasis to bone and soft organs, can easily be
      extended to other cell/marker/organ systems, and should also find application in
      preclinical assessment of anti-metastatic modalities.

PMID- 12198767
TI  - A new liver metastatic and peritoneal dissemination model established from the
      same human pancreatic cancer cell line: analysis using cDNA macroarray.
AB  - To elucidate the mechanisms of metastasis, we established two sublines HPC-1H5
      with a highly liver metastatic cell line and HPC-1P5a with a highly peritoneal
      disseminating cell line, which were sequentially selected from the parental
      pancreatic cancer cell line HPC-1. Using these three cell lines, we investigated
      several biological properties and mRNA levels of differentially-expressed genes
      involved in cancer metastasis by cDNA macroarray. Microscopic findings for the
      three cell lines were the same. The tumorigenicity, in vitro growth ability,
      motile activity, adhesive activity and the production of IL-8 of metastatic
      sublines were higher than those of parental HPC-1 cells. Particularly, HPC-1H5
      cells showed clearly higher levels of IL-8 expression and tumors of HPC-1H5 cells
      grew faster and bigger than those of HPC-1P5a cells. In cDNA macroarray analysis
      of HPC-1H5 cells, 22 genes were up-regulated and 44 genes were down-regulated
      compared with parental HPC-1 cells. In HPC-1P5a cells, 9 genes were up-regulated
      and 28 genes were down-regulated compared with parental HPC-1 cells. This study
      provides a demonstration of global gene expression analysis of pancreatic cancer
      cells with liver metastasis and peritoneal dissemination. Furthermore, our
      results provide a new insight into the study of liver metastasis and peritoneal
      dissemination of human pancreatic cancer.

PMID- 12198768
TI  - Overexpression of c-erbB-2 protein correlates with chromosomal gain at the c-erbB
      2 locus and patient survival in advanced colorectal carcinomas.
AB  - Overexpression of the c-erbB-2 protein (also called HER-2/neu) is observed in a
      variety of malignancies including colorectal cancer (CRC). In this study we aimed
      to evaluate the rate of c-erbB-2 overexpression in our tumor collection and to
      clarify its correlation with the chromosomal status at the c-erbB-2 locus in CRC.
      Additionally we correlated the c-erbB-2 overexpression and the chromosomal gain
      of 17q with patient survival. Seventy-four specimens were analyzed
      immunohistochemically using a polyclonal c-erbB-2 antibody (DAKO) and the
      staining was scored according to the Clinical Trial Assay recommendations (0-3+).
      Of these, 45 cases were analyzed by comparative genomic hybridization (CGH) and
      immunohistochemistry (IHC). Overexpression was observed in 51% of the cases
      (score > or = 2). Chromosomal gains at the c-erbB-2 locus were clearly correlated
      with overexpression of the gene (P = 0.0009). Furthermore Kaplan-Meier analysis
      showed that overexpression of c-erbB-2 was significantly associated with poor
      survival and thus could serve as a prognostic marker. We conclude that c-erbB-2
      is related with tumor progression in CRC which can be observed on protein level
      and reflects chromosomal gain at the locus at 17q.

PMID- 12198769
TI  - Protein phosphatase-2A modulates the serine and tyrosine phosphorylation of
      paxillin in Lewis lung carcinoma tumor variants.
AB  - Cellular adhesion and motility, processes regulated by focal adhesion assembly
      and disassembly, can influence a tumor cell's ability to metastasize. Focal
      adhesion dynamics are, in turn, influenced by the serine and tyrosine
      phosphorylation state of paxillin. Using Lewis lung carcinoma (LLC) tumor
      variants, this study shows the importance of the serine/threonine protein
      phosphatase-2A (PP-2A) in maintaining adherence and restricting tumor cell
      motility, and modulating the serine and tyrosine phosphorylation of paxillin.
      Treating non-metastatic LLC-C8 tumor variants with okadaic acid to inhibit PP-2A
      activity resulted in cell rounding and increased motility. These effects on
      motility and adherence were accompanied by increased serine and decreased
      tyrosine phosphorylation of paxillin. These results suggest PP-2A regulation of
      paxillin phosphorylation may have a role in controlling tumor cell adherence and
      motility.

PMID- 12198770
TI  - Gene transduction of NK4, HGF antagonist, inhibits in vitro invasion and in vivo
      growth of human pancreatic cancer.
AB  - In this study, we investigated the therapeutic effects of adenovirally-mediated
      transfer of the sequence of NK4, an antagonist for hepatocyte growth factor
      (HGF), against human pancreatic carcinoma. HGF has been implicated to play an
      important role in invasion and metastasis of various human cancers through tumor
      stromal interactions. Although NK4 has been shown to block the metastatic
      behavior of cancer cells, problems with cellular delivery of NK4 must be
      addressed before it can be used for clinical trials. The effects of NK4 gene
      transduction mediated by recombinant adenovirus (Ad-NK4) were evaluated in a
      human pancreatic cancer cell line (SUIT-2) by in vitro scattering assays,
      invasion assays, and subcutaneous transplantation in nude mice. NK4 transduction
      markedly inhibited scattering and invasion of SUIT-2 cells stimulated by HGF
      without affecting cell proliferation in vitro. Furthermore, Ad-NK4 significantly
      inhibited the growth of tumors transplanted to nude mice. The tumor reduction
      induced by Ad-NK4 was associated with a decreased number of blood vessels
      surrounding the tumors. These findings suggest that Ad-NK4 gene therapy may be a
      unique and promising strategy for the treatment of pancreatic cancer.

PMID- 12198771
TI  - Involvement of tumor cell integrin alpha v beta 3 in hematogenous metastasis of
      human melanoma cells.
AB  - Early metastasis is the primary cause of death in melanoma patients. The adhesion
      receptor integrin alpha v beta 3 contributes to tumor cell functions that are
      potentially involved in melanoma growth and metastasis. We tested whether
      integrin alpha v beta 3 supports metastasis of human melanoma cells when injected
      into the bloodstream of immune deficient mice. Comparing variants of the same
      melanoma cell type that expressed either alpha v beta 3, alpha IIb beta 3 or no
      beta 3 integrin, we found that only alpha v beta 3 strongly supported metastasis.
      Inhibition of tumor cell alpha v beta 3 function reduced melanoma metastasis
      significantly and prolonged animal survival. To understand mechanisms that allow
      alpha v beta 3, but not alpha IIb beta 3 to support melanoma metastasis, we
      analyzed proteolytic and migratory activities of the melanoma cell variants.
      Melanoma cells expressing alpha v beta 3, but not those expressing alpha IIb beta
      3 or no beta 3 integrin, produced the active form of metalloproteinase MMP-2 and
      expressed elevated mRNA levels of MT1-MMP and TIMP-2. This indicates an
      association between alpha v beta 3 expression and protease processing.
      Furthermore, alpha v beta 3 expression was required for efficient melanoma cell
      migration toward the matrix proteins fibronectin and vitronectin. The results
      suggest that expression of integrin alpha v beta 3 promotes the metastatic
      phenotype in human melanoma by supporting specific adhesive, invasive and
      migratory properties of the tumor cells and that the related integrin alpha IIb
      beta 3 cannot substitute for alpha v beta 3 in this respect.

PMID- 12198772
TI  - Decreased expression of intercellular adhesion molecule-1 (ICAM-1) and urokinase
      type plasminogen activator receptor (uPAR) is associated with tumor cell
      spreading in vivo.
AB  - The development of an effective antitumor immune response to control tumor growth
      is influenced by the tumor cell itself and/or by the tumor microenvironment.
      Tumor invasion and tumor cell spreading require a finely tuned regulation of the
      formation and loosening of adhesive contacts of tumor cells with the
      extracellular matrix (ECM). In our laboratory, a rat tumor cell line derived from
      a spontaneous rat sarcoma revealed, by flow cytometry, a high frequency of
      intercellular adhesion molecule-1 (ICAM-1, 70.1 +/- 8.7%) and urokinase-type
      plaminogen activator receptor (uPAR, 51.2 +/- 5.2%) positive cells, while a weak
      expression of MHC class II (IA, 2.2 +/- 0.2% and IE, 17.4 +/- 3.7%) and B7 (12.1
      +/- 2.2%) antigens was detected. In our tumor experimental model, after
      implantation of tumor cells, visible tumor masses were present at days 5-7 with a
      relatively fast tumor growth until day 15 (progressive phase) followed by a
      suppression of the tumor growth (regressive phase). Here we present data that
      correlates a significant decrease in the frequency of ICAM-1 and uPAR expressing
      tumor cells with the appearance of tumor cells in sites distant from that of the
      primary tumor. In addition we describe the development of a cellular immune
      response which controls the tumor progression and is associated with an increase
      in the expression of major histocompatibility complex (MHC) class II IA antigen
      during tumor development. The histological examination at tumor progressive and
      regressive time points revealed the relevant presence of polymorphonuclear
      neutrophils (PMNs) evidencing colliquative necrosis in tumor growth areas. Taken
      together, these results support the idea that the balance between adhesive
      interactions, proteolytic activity and tumorigenicity may lead to a tumor
      invasive phenotype.

PMID- 12198773
TI  - Differential expression of CD44(S) and variant isoforms v3, v10 in three
      dimensional cultures of mouse melanoma cell lines.
AB  - Multi-cellular spheroids (MCS) generated from tumor cells serve as excellent in
      vitro models for understanding the mechanisms of tumor progression and micro
      metastasis. We have compared the expression of molecular markers with reference
      to their growth as conventional adherent monolayers (2-D) and anchorage
      independent cultures (3-D) using two mouse melanoma cell lines, B16F10 and Clone
      M3. The two cell lines differed in their ability to form spheroids with respect
      to their aggregation potential, with B16F10 forming large clusters compared to
      Clone M3. A panel of molecular markers comprising cell adhesion molecules, cyclin
      dependent kinase inhibitors and members of the cadherin-catenin complex were
      analyzed by flow cytometry in 2-D and 3-D cultures. There was a distinct
      difference in the patterns of expression of CD44(S) and variant isoforms v3, v10
      in spheroids compared to cells grown as monolayers in both cell lines. Also,
      there was an increase in cells positive for CDK inhibitor p27 in 3-D cultures
      from the B16F10 cell line. The expression of alpha and gamma catenin was down
      regulated in spheroids. As these molecules are implicated in the regulation of
      cell proliferation, alterations in the expression of these molecules in 3-D
      cultures compared to their 2-D counterparts suggests the importance of spheroids
      as experimental model for tumorigenesis.

PMID- 12198775
TI  - On the nature of implicit categorization.
AB  - Current categorization models disagree about whether people make a priori
      assumptions about the structure of unfamiliar categories. Data from two
      experiments provided strong evidence that people do not make such assumptions.
      These results rule out prototype models and many decision bound models of
      categorization. We review previously published neuropsychological results that
      favor the assumption that category learning relies on a procedural-memory-based
      system, rather than on an instance-based system (as is assumed by exemplar
      models). On the basis of these results, a new category-learning model is proposed
      that makes no a priori assumptions about category structure and that relies on
      procedural learning and memory.

PMID- 12198774
TI  - Negative correlation between the ratio of Bax to Bcl-2 and the size of tumor
      treated by culture supernatants from Kupffer cells.
AB  - Kupffer cells play an important role in keeping liver from occurrence of tumors.
      Apoptosis is thought to be a major mechanism responsible for the anti-tumor
      function of Kupffer cells. Previous studies have mainly concentrated on the
      direct contact and interaction between Kupffer cells and tumor cells. The present
      experiment is to investigate the apoptotic pathway in tumor induced by culture
      supernatant from activated Kupffer cells. The levels of Bax, Bcl-2 and iNOS were
      analyzed in an in vivo mouse tumor model, which was treated with culture
      supernatant from activated Kupffer cells. The results showed that the expression
      of Bax significantly increased while the expression of Bcl-2 decreased when tumor
      cells were treated with culture supernatants from activated Kupffer cells. The
      alteration of Bax and Bcl-2 levels resulted in an increase in the ratio of Bax to
      Bcl-2, which had negative correlation with the size of tumor and positive
      correlation with the expression of iNOS. The expression of TNF alpha and the
      occurrence of apoptosis were also increased in tumor treated with culture
      supernatants from activated Kupffer cells, compared with those which received no
      treatment. In conclusion, culture supernatants from activated Kupffer cells were
      able to change the balance between Bax and Bcl-2 in favor of the former. The
      ratio of Bax to Bcl-2 is a useful index to evaluate tumor apoptosis induced by
      Kupffer cells. Our experiment also suggests that alteration of the ratio of Bax
      to Bcl-2 may result from increased levels of iNOS and TNF alpha.

PMID- 12198776
TI  - Sparkling at the end of the tongue: the etiology of tip-of-the-tongue
      phenomenology.
AB  - The tip-of-the-tongue experience (TOT) is the phenomenological experience that a
      currently inaccessible word is stored in memory and will be retrieved. TOTs
      appear to be a universal experience that occurs frequently in everyday life,
      making the TOT an ideal case study in human phenomenology. This paper considers
      TOTs in light of Tulving's (1989) challenge to the doctrine of concordance, which
      is the assumption that behavior, cognition, and phenomenology are correlated, if
      not caused by identical processes. Psycholinguistic and memory theories,
      consistent with concordance, argue for direct access, or the view that TOTs and
      word retrieval are caused by the same retrieval processes. The metacognition view
      challenges concordance and views TOTs as an inference based on nontarget
      information that is accessible to rememberers. Current data, reviewed here,
      suggest that TOTs are caused via direct access and through inferential processes.
      Dissociations between TOTs and retrieval suggest that the causes of TOT
      phenomenology and the processes of retrieval are not identical.

PMID- 12198777
TI  - A front end to a theory of picture recognition.
AB  - We describe the results of four picture-recognition memory experiments in which
      we systematically manipulated four variables: stimulus duration, stimulus
      contrast, the duration of a blank gap between successive presentations of the
      same stimulus, and the presence or absence of a noise mask that immediately
      followed stimulus offset. The patterns of obtained data confirmed a simple
      extension of a theory previously used to account for digit recall data. This
      theory consists of a low-pass linear-filter front end that generates a sensory
      response from the physical stimulus, followed by an information-sampling process
      whose instantaneous sampling rate is based in part on the sensory response
      magnitude. The data confirm both qualitative and quantitative theoretical
      predictions, some of which were previously untestable in digit recall tasks
      because of ceiling effects that were not present in our picture-recognition
      tasks. We describe the role of our theory within the broader family of picture
      memory theories, and we briefly discuss our theory's unification of two salient
      facets of visual behavior: information acquisition on the one hand, and
      phenomenological appearance on the other hand.

PMID- 12198779
TI  - Recovery from one-trial overshadowing.
AB  - Prevailing models of associative learning can all account for multitrial
      overshadowing. However, they fail to account for one-trial overshadowing, which
      is ordinarily explained in terms of distraction of the subject by the more
      salient of two simultaneously trained cues from the less salient cue, which
      interferes with associative acquisition. In the present study, we demonstrate
      that recovery from overshadowing can be obtained through two techniques that have
      previously been found to restore responding to overshadowed cues in multitrial
      training situations. Specifically, recovery from one-trial overshadowing was
      obtained by extinguishing the overshadowing stimulus and also by administering a
      posttraining reminder treatment consisting of brief exposure to the overshadowed
      cue. The similarity of these observations to those in multitrial overshadowing
      suggests that one-trial and multitrial overshadowing arise from a common
      underlying mechanism and further augments the view that all cue competition is
      due (at least in part) to a failure to express acquired information, rather than
      to a failure to learn.

PMID- 12198780
TI  - The attentional blink with targets in different spatial locations.
AB  - When two targets (T1 and T2) are displayed in rapid succession, accuracy of T2
      identification varies as a function of the temporal lag between the targets
      (attentional blink, AB). In some studies, performance has been found to be most
      impaired at Lag 1--namely, when T2 followed T1 directly. In other studies, T2
      performance at Lag 1 has been virtually unimpaired (Lag 1 sparing). In the
      present work, we examined how Lag 1 sparing is affected by attentional switches
      between targets displayed in the same location or in different locations. We
      found that Lag 1 sparing does not occur when a spatial shift is required between
      T1 and T2. This suggests that attention cannot be switched to a new location
      while the system is busy processing another stimulus. The results are explained
      by a modified version of an attentional gating model (Chun & Potter, 1995;
      Shapiro & Raymond, 1994).

PMID- 12198778
TI  - The role of US signal value in contingency, drug conditioning, and learned
      helplessness.
AB  - In Pavlovian conditioning, organisms can learn that a conditioned stimulus (CS)
      signals the delivery of an unconditioned stimulus (US). The present paper first
      reviews research showing that organisms can also learn that a stimulus, normally
      considered to be a US, signals the delivery of another US. Second, the paper
      shows how such signal value may contribute to three conditioning phenomena that
      are of interest to many psychologists: contingency, drug conditioning, and
      learned helplessness. In addition to showing how such signal value may contribute
      to these three phenomena, suggestions for further research, as well as current
      gaps in the knowledge base, are outlined.

PMID- 12198781
TI  - Response times to Ehrenstein illusions of varying subjective magnitude:
      complementarity of psychophysical measures.
AB  - The following experiments investigate the effects of contrast polarity, inducer
      spacing, and inducer type on three dependent variables measuring the perception
      of an illusory surface in Ehrenstein figures: subjective magnitude, response
      time, and frequency of perception. It was found that response time generally
      decreased when the other two behavioral indicators increased. However, it was
      also shown that subjective magnitude provided more discriminating measures of
      relatively strong illusory percepts, whereas frequency of perception and response
      time provided more discriminating measures of relatively weak illusory percepts.
      The findings generally confirm earlier work on the effect of inducer spacing and
      contrast polarity on the perceived strength of brightness illusions, and in
      particular reveal the complementarity of subjective magnitude, response time, and
      frequency of perception as critical measures of configurational effects in the
      perceptual processing of these phenomena.

PMID- 12198782
TI  - Do images involuntarily trigger search? A test of Pillsbury's hypothesis.
AB  - Pillsbury (1908) suggested that deciding to search for something in a scene
      consists of nothing more than forming a visual image of the target. If so,
      imaging should trigger search even when it would be more advantageous not to
      search. Subjects were cued to form an image of a specified object (e.g., tiger)
      and to press a key when they had done so. This initiated the presentation of a
      sequence of pictures, with a single target digit interspersed; the subject's task
      was to report this digit. The sequence contained a picture of the same type of
      object that the subject had just imaged (e.g., a tiger), either before or after
      the target digit. If this picture was detected involuntarily, an attentional
      blink should have impaired digit detection when the picture preceded the digit.
      This was confirmed in two experiments, even when instructions specifically
      encouraged subjects to discard the image and to avoid searching for it. The
      results support Pillsbury's hypothesis.

PMID- 12198784
TI  - A position-sensitive Stroop effect: further evidence for a left-to-right
      component in print-to-speech conversion.
AB  - In the classical Stroop effect, response times for naming the color in which a
      word is printed are affected by the presence of semantic, phonological, or
      orthographic relationships between the stimulus word and the response word. We
      show that color naming responses are faster when the printed word shares a
      phoneme with the color name to be produced than when it does not, in conditions
      where there is no semantic relationship between the printed word and the color
      name. This result is compatible with a variety of computational models of
      reading. However, we also found that these effects are much larger when it is the
      first phoneme that the stimulus and response share than when it is the last. Our
      data are incompatible with computational models of reading in which the
      computation of phonology from print is purely parallel. The dual route cascaded
      model computational model of reading, which has a lexical route that operates in
      parallel and a nonlexical route that operates serially letter by letter,
      successfully simulates this position-sensitive Stroop effect. The model also
      successfully simulates the "onset effect" in masked priming (Forster & Davis,
      1991) and the interaction between the regularity effect and the position in a
      word of a grapheme-phoneme irregularity (Rastle & Coltheart, 1999b)--effects
      which, we argue, arise for the same reason as the position-sensitive Stroop
      effect we report.

PMID- 12198783
TI  - Unconsciously controlled processing: the Stroop effect reconsidered.
AB  - The Stroop effect is widely considered to be compelling evidence that an acquired
      skill such as reading is "automatic" in the sense that lexical/semantic analyses
      of single words cannot be prevented, even when they are irrelevant and harmful to
      the task at hand. This view is challenged by a series of three experiments in
      which the presence/absence of a Stroop effect depends on (1) whether all of the
      target elements are colored or not, in conjunction with (2) whether the target
      and the spatially distinct color word distractor belong to the same domain or
      not. A framework is offered in which domain-specific encoding algorithms play a
      major role. Skilled word recognition is typically unconscious, but is
      characterized better as contextually controlled, rather than "automatic."

PMID- 12198785
TI  - Sex differences in visuospatial working memory: components of cognitive
      processing.
AB  - Numerous studies have shown that sex differences in visuospatial tasks vary in
      size and direction depending on the nature of the task, with large differences
      favoring males on tasks that require transformations in visuospatial working
      memory. The cognitive processes underlying these differences were investigated
      using laboratory tasks developed by Dror and Kosslyn (1994). Four cognitive
      components of visuospatial working memory were assessed--image generation,
      maintenance, scanning, and transformation--in an attempt to identify the
      components that would show differential effects for females and males. The image
      generation task required retrieval of shape information from long-term memory,
      generation of a visual image in working memory, and utilization of the
      information about the shape in a decision task. The image maintenance task
      required only the latter two processes. The information processing demands
      required by scanning and rotation tasks came from the need to transform the
      visual image so that it could be used in decision making. Males responded more
      quickly on all four tasks (ds between .63 and .77), with no between-sex
      differences in accuracy. We concluded that speed of processing is central to
      understanding sex differences in visuospatial working memory. We discuss
      implications of these findings for performance on real-world visuospatial tasks.

PMID- 12198786
TI  - Memory for psychophysical scaling judgments.
AB  - In three experiments, we examined memory for responses and stimuli experienced in
      a single direct psychophysical scaling session in which subjects made absolute
      magnitude estimations of the loudnesses of pure tones. Recall of scaling
      responses was found to be accurate for the softest and loudest stimuli, but
      systematically greater than actual judgments for the intermediate stimulus
      amplitudes, yielding distorted psychophysical functions for the recall data which
      nonetheless had the same power function exponent as that for the judged stimuli.
      Also, memory for the range of stimulus amplitudes was fairly accurate, but
      subjects could not distinguish between judged and nonjudged amplitudes within
      that range. The results are consistent with the role of extreme stimuli as
      anchors for judgment, and indicate that memories for these stimuli and responses
      made to them can be expected to influence future scaling judgments. These results
      also are consistent with the uncertainty hypothesis of mnemophysics.

PMID- 12198787
TI  - Primacy and recency in primed free association and associative cued recall.
AB  - Two experiments compared the serial positions of primed words in an implicit free
      association test with words recalled in a cued recall test. In both tests, weakly
      or strongly related word pairs were studied, and the first words of each pair
      formed the test cues. In the implicit test, weakly related words pairs showed
      primacy and extended recency effects but strongly related word pairs did not. In
      the explicit test, both weakly and strongly related word pairs showed primacy and
      extended recency effects. These functional dissociations between implicit and
      explicit memory tests indicate that strongly related word pairs are encoded
      together because they have unitized memory representations that function as
      integrated units without requiring any additional associative links to be made,
      but that an additional system or process is required to strengthen weakly related
      word pairs during encoding. In addition, a further additional system or process
      is accessed by explicit retrieval.

PMID- 12198788
TI  - Literal and figurative interpretations are computed in equal time.
AB  - The time courses for constructing literal and figurative interpretations of
      simple propositions were measured with the response signal, speed-accuracy
      tradeoff procedure. No differences were found in comprehension speed for literal
      and figurative strings in a task that required judging whether a string of words
      was meaningful. Likewise, no differences were found in processing speed for
      nonsense and figurative strings in a task that required judging whether a string
      of words was literally true. Figurative strings were less likely to be judged
      meaningful than were literal strings and less likely to be rejected as literally
      true than were nonsense strings. The absence of time-course differences is
      inconsistent with approaches to figurative processing that contend that a
      figurative interpretation is computed after an anomalous literal interpretation.
      The time-course profiles suggest that literal and figurative interpretations are
      computed in equal time but that the meaning of the latter is less constrained
      than that of the former.

PMID- 12198789
TI  - Learning categories at different hierarchical levels: a comparison of category
      learning models.
AB  - Three formal models of category learning, the rational model (Anderson, 1990),
      the configural-cue model (Gluck & Bower, 1988a), and ALCOVE (Kruschke, 1992),
      were evaluated on their ability to account for differential learning of
      hierarchically structured categories. An experiment using a theoretically
      challenging category structure developed by Lassaline, Wisniewski, and Medin
      (1992) is reported. Subjects learned one of two different category structures.
      For one structure, diagnostic information was present along a single dimension (1
      D). For the other structure, diagnostic information was distributed across four
      dimensions (4-D). Subjects learned these categories at a general or at a specific
      level of abstraction. For the 1-D structure, specific-level categories were
      learned more rapidly than general-level categories. For the 4-D structure, the
      opposite result was observed. These results proved highly diagnostic for
      evaluating the models--although ALCOVE provided a good account of the observed
      results, the rational model and the configural-cue model did not.

PMID- 12198790
TI  - Can a machine tickle?
AB  - It has been observed at least since the time of Aristotle that people cannot
      tickle themselves, but the reason remains elusive. Two sorts of explanations have
      been suggested. The interpersonal explanation suggests that tickling is
      fundamentally interpersonal and thus requires another person as the source of the
      touch. The reflex explanation suggests that tickle simply requires an element of
      unpredictability or uncontrollability and is more like a reflex or some other
      stereotyped motor pattern. To test these explanations, we manipulated the
      perceived source of tickling. Thirty-five subjects were tickled twice--once by
      the experimenter, and once, they believed, by an automated machine. The reflex
      view predicts that our "tickle machine" should be as effective as a person in
      producing laughter, whereas the interpersonal view predicts significantly
      attenuated responses. Supporting the reflex view, subjects smiled, laughed, and
      wiggled just as often in response to the machine as to the experimenter. Self
      reports of ticklishness were also virtually identical in the two conditions.
      Ticklish laughter evidently does not require that the stimulation be attributed
      to another person, as interpersonal accounts imply.

PMID- 12198791
TI  - Strength of context does modulate the subordinate bias effect: a reply to Binder
      and Rayner.
AB  - Using a self-paced reading task, Kellas, Martin, Yehling, Herman, and Vu (1995)
      demonstrated that strength of context can modulate the effects of meaning
      frequency. Binder and Rayner (1998) initially replicated the results, using eye
      tracking methodology. On further examination of the stimuli, Binder and Rayner
      eliminated 43% of the stimulus set and found that context strength failed to
      modulate meaning frequency. Binder and Rayner's initial replication of Kellas et
      al. and the convergence of results between their two main experiments established
      the validity of self-paced reading as a measure of on-line reading, when compared
      with eye-tracking methodology. However, their central conclusion, that context
      strength cannot modulate the subordinate bias effect, is open to question. In
      this commentary, we examine the criteria adopted to exclude items from our
      homonym set and discuss the issue of local versus published norms. We also
      discuss the issue of context strength, as related to the specific rating
      procedures employed. Finally, we conclude that strong context can, in fact,
      eliminate the subordinate bias effect and that the context-sensitive model can
      more fully account for the available data on lexical ambiguity resolution.

PMID- 12198792
TI  - Germs in space. Joshua Lederberg, exobiology, and the public imagination, 1958
      1964.
AB  - Under the leadership of Joshua Lederberg, some American biologists and chemists
      proposed exobiology as the most legitimate program for space research. These
      scientists used the fear of contamination--of earth and other planets--as a
      central argument for funding "nonpolitical," "scientifically valid" experiments
      in extraterrestrial life detection. Exobiology's resemblance to popular science
      fiction narratives presented a significant challenge to its advocates' scientific
      authority. Its most practical applications, moreover, bore an unseemly
      resemblance to the United States Army's research on biological weapons. At the
      same time that exobiologists wanted to use the media to attract support for their
      program, they had to monitor their statements carefully in order to maintain
      their view of exobiology as a peaceful, scientifically valid research program. In
      examining how exobiology's creators positioned their work in comparison to other
      space sciences as well as science fiction, this case study highlights how
      cultural and political imperatives entered science through practice and narrative
      during the Cold War.

PMID- 12198793
TI  - Natural history of parasitic disease. Patrick Manson's philosophical method.
AB  - A distinct British approach to disease in the tropics has been identified in the
      recent historiography of colonial medicine: Mansonian tropical medicine, named
      after Sir Patrick Manson (1844-1922), the founder of the London School of
      Tropical Medicine. This essay examines Manson's study of filariasis (infection
      with the filarial nematode worm) and argues that his conceptual tools and
      research framework were derived from contemporary natural history. It
      investigates Manson's training in natural history at the University of Aberdeen,
      where some of his teachers were closely associated with transcendental biology.
      The concepts of perfect adaptation and the harmony of nature were crucial to the
      formulation of his research problematic. This essay demonstrates that
      biogeographical concepts played an important part in Manson's research
      methodology. It also investigates how Manson's natural historical approach
      contributed to the making of so-called Mansonian tropical medicine.

PMID- 12198794
TI  - Nuclear democracy. Political engagement, pedagogical reform, and particle physics
      in postwar America.
AB  - The influential Berkeley theoretical physicist Geoffrey Chew renounced the
      reigning approach to the study of subatomic particles in the early 1960s. The
      standard approach relied on a rigid division between elementary and composite
      particles. Partly on the basis of his new interpretation of Feynman diagrams,
      Chew called instead for a "nuclear democracy" that would erase this division,
      treating all nuclear particles on an equal footing. In developing his rival
      approach, which came to dominate studies of the strong nuclear force throughout
      the 1960s, Chew drew on intellectual resources culled from his own political
      activities and his attempts to reform how graduate students in physics would be
      trained.

PMID- 12198795
TI  - Processing human brain tissue for in situ hybridization with radiolabelled
      oligonucleotides.

PMID- 12198796
TI  - In situ hybridization of astrocytes and neurons cultured in vitro.

PMID- 12198797
TI  - In situ hybridization on organotypic slice cultures.

PMID- 12198798
TI  - Quantitative analysis of in situ hybridization histochemistry.

PMID- 12198799
TI  - Non-radioactive in situ hybridization using alkaline phosphatase-labelled
      oligonucleotides.

PMID- 12198800
TI  - Combining non-radioactive in situ hybridization with immunohistological and
      anatomical techniques.

PMID- 12198801
TI  - Non-radioactive in situ hybridization: simplified procedures for use in whole
      mounts of mouse and chick embryos.

PMID- 12198802
TI  - In situ hybridization with oligonucleotide probes.

PMID- 12198803
TI  - Cryostat sectioning of brains.

PMID- 12198805
TI  - Processing retinal tissue for in situ hybridization.

PMID- 12198804
TI  - Processing rodent embryonic and early postnatal tissue for in situ hybridization
      with radiolabelled oligonucleotides.

PMID- 12198806
TI  - Processing the spinal cord for in situ hybridization with radiolabelled
      oligonucleotides.

PMID- 12198807
TI  - Introduction: studying gene expression in neural tissues by in situ
      hybridization.

PMID- 12198808
TI  - Neurofilaments in diabetic neuropathy.
AB  - This review discusses the role of abnormal neurofilament (NF) expression,
      processing, and structure as an etiological factor in diabetic neuropathy.
      Diabetic sensory and autonomic neuropathy in humans is associated with a spectrum
      of structural changes in peripheral nerve that includes axonal degeneration,
      paranodal demyelination, and loss of myelinated fibers-- the latter is probably
      the result of a dying-back of distal axons. NF filaments are composed of three
      subunit proteins, NFL, NFM, and NFH, and are major constituents of the axonal
      cylinder. It is clear that any abnormality in synthesis, delivery, or processing
      of these critical proteins could lead to severe impairments in axon structure and
      function. This article describes mechanisms of synthesis, phosphorylation, and
      delivery of NF and discusses how these processes may be abnormal in diabetics.
      The pathological alterations in the ganglion and preipheral nerve that occur in
      sensory and autonomic neuropath will be outlined and related to possible abnormal
      processing of NF. A major focus is the role or aberrant NF phosphorylation and
      its possible involvement in the imparied delivery of NF to the distal axon.
      Identification of stress-activated protein kinases (SAPKs) as NF kinases is
      discussed in detail and it is proposed that hyperglycemia-induced activation of
      SAPKs may be a primary etiological event in diabetic neuropathy.

PMID- 12198809
TI  - Apoptosis in diabetic neuropathy.
AB  - It has been proposed that apoptotic death of some sensory neurons and Schwann
      cells occurs in, and may be causal for, diabetic neuropathy (DN). Some
      tantalizing but incomplete evidence for this has emerged from studies of rat
      models of diabetes and in vitro studies of sensory and sympathetic neurons and
      Schwann cells exposed to very high concentrations of glucose. This article
      reviews the evidence and suggests that most studies to date are far from being
      conclusive. Hence there is room for proper studies of apoptosis in DN, as such
      studies may reveal hitherto unexplored drug targets that may improve management
      of the disease.

PMID- 12198810
TI  - Nerve and ganglion blood flow in diabetes: an appraisal.
AB  - Vasa nervorum, the vascular supply to peripheral nerve trunks, and their
      associated cell bodies in ganglia have unique anatomical and physiological
      characteristics. Several different experimental approaches toward understanding
      the changes in vase nervorum following injury and disease have been used.
      Quantative techniques most widely employed have been microelectrode hydrogen
      clearance palarography and [14C]iodoantipyrine autoradiographic distribution,
      whereas estimates of red blood cell flux using a fiber-optic laser Doppler probe
      offer real time data at different sites along the nerve trunk. There are
      important caveats about the use of these techniques, their advantages, and their
      limitations. Reports of nerve blood flow require careful documentation of
      physiological variables, including mean arterial pressure and nerve temperature
      during the recordings. Several ischemic models of the peripheral nerve trunk have
      addressed the ischemic threshold below which axonal degeneration ensues (<
      5ml/100 g/min). Following injury, rises in local blood flow reflect acitons of
      vasoactive peptides, nitric oxide, and the development of angiogenesis. In
      experimental diabetes, a large number of studies have documented reductions in
      nerve blood flow and tandem corrections of nerve blood flow and conduction
      slowing. A significant proportions, however, of the work can be criticized on the
      basis of methodology and interpretation. Similarly, not all work has confirmed
      that reductions of nerve blood flow are an invariable feature of experimental or
      human diabetic polyneuropathy. Therefore, while there is disagreement as to
      whether early declines in nerve blood flow "account" for diabetic polyneuropathy,
      there is unquestioned eveidence of early microangiopathy. Abnormalities of vase
      nervorum and micorvessels supplying ganglia at the very least develop parallel to
      and together with changes in neurons, Schwann cells, and axons.

PMID- 12198811
TI  - Potential mechanisms of neuropathic pain in diabetes.
AB  - Abnormal sensations and pain are features of approximately 10% of all cases of
      diabvetic neuropathy and can cause marked diminution in the quality of life for
      these patients. The quality and distribution of pain are variable, although
      descriptions of burning pain in the hands and feet are commonly reported. Like
      other neuropathic pain states, painful diabetic neuropathy has an unknown
      pathogenesis and, in many cases, is not alleviated by nonsteriodal anti
      inflammatory drugs or opiates. In the last decase, a number of behavioral and
      physiologic studies have revealed indices of sensory dysfunction in animal models
      of diabetes. These include hyperalgesia to mechanical and noxious chemical
      stimuli and allodynia to light touch. Animal models of painful diabetic
      neuropathy have been used to investigate the therapeutic potential of a range of
      experimental agents and also to explore potential etiologic mechanisms. There is
      relatively little evidence to suggest that the peripheral sensory nerves of
      diabetic rodents exhibit spontaneous activity or increased responsiveness to
      peripheral stimuli. Indeed, the weight of eveidence suggests that sensory input
      to the spinal cord is decreased rather than increased in diabetic rodents.
      Aberrant spinal or supraspinal modulation of sensory processing may therefore be
      involved in generating allodynia and hyperalgesia in these models. Studies have
      supported a role for spinally mediated hyeralgesia in diabetic rats that may
      reflect either a response to diminished peripheral input or a consequence of
      hyperglycemia on local or descending modulatory systems. Elucidating the affects
      of diabetes on spinal sensory processing may assist development of novel
      therapeutic strategies for preventing and alleviating painful diabetic
      neuropathy.

PMID- 12198812
TI  - Electrophysiologic measures of diabetic neuropathy: mechanism and meaning.
AB  - Whole nerve electrophysiologic procedures afford a battery of measures that can
      provide a noninvasive and objective index of the onset and progression of
      diabetic polyneuropathy (DPN). Advances in physiologic procedures, digital
      hardware, and mathematical models have allowed assessment of activity in slower
      conducting fibers, as well as measures that reflect changes in refractory periods
      and threshold excitability. These expanded options can augment standard measures
      of maximal conduction velocity and compound amplitude and greatly enhance the
      sensitivity of whole nerve measure to both structural (e.g. demyelination) and
      "nonstructural" (e.g. redistribution of ion channels) deficits associated with
      DPN. The mechanisms underlying the physiologic events in DPN are multifactorial
      and their sequence in complex, with different mechanisms contributing to change
      at overlapping, but distinct points in the progression. Factors influencing early
      change in velocity may differ from those contributing to chronic deficits and
      these mechanisms may also differ in their response to various putative therapies.
      This review attempts to summarize the pattern of whole nerve electrophysiologic
      change associated with DPN, outlines the strengths and limitations of the various
      measures that are feasible, and discusses the specific impact of know
      pathophysiologic mechanisms on these end points.

PMID- 12198813
TI  - Neuropathology and pathogenesis of diabetic autonomic neuropathy.
AB  - Autonomic neuropathy is a significant complication of diabetes resulting in
      increased patient morbidity and mortality. A number of studies, which have shown
      correspondence between neuropathologic findings in experimental animals and human
      subjects, have demonstrated that axonal and dendritic pathology in sympathetic
      ganglia in the absence of significant neuron loss represents a neuropathologic
      hallmark of diabetic autonomic neuropathy. A recurring theme in sympathetic
      ganglia, as well as in the pot-ganglionic autonomic innervation of various end
      organs, is the involvement of distal portions of axons and nerve terminals by
      degenerative or dystrophic changes. In both animals and humans, there is a
      surprising selectivity of the diabetic process for subpopulations of autonomic
      ganglia, nerve terminals within sympathetic ganglia and end organs, from end
      organ to end organ, and between vascular and other targets within individual end
      organs. Although the involvement or autonomic axons in somatic nerves may reflect
      an ischemic pathogenesis, the selectivity of the diabetic process confounds
      simple global explanations of diabetic autonomic neuropathy as the result of
      diminished blood flow with resultant tissue hypoxia. A single unifying
      pathogenetic hypothesis has not yet emerged from clinical and experimental animal
      studies, and it is likely that diabetic autonomic neuropathy will be shown to
      have multiple causative mechanisms, which will interact to result in the variety
      of presentations of autonomic injury in diabetes. Some of these mechanisms will
      be shared with aging changes in the autonomic nervous system. The role of various
      neurotrophic substances and the polyol pathway in the pathogenesis and treatment
      of diabetic neuropathy likely represents a two-edged sword with both salutary and
      exacerbating effects. The basic neurobiologic process underlying the diabetes
      induced development of neuroaxonal dystrophy, synaptic dysplasia, defective
      axonal regeneration, and alterations in neurotrophic substance may be
      mechanistically related.

PMID- 12198814
TI  - Role of the Schwann cell in diabetic neuropathy.
AB  - The relationships among Schwann cells, axons, and the perineurial barrier
      emphasize the key role Schwann cells play in normal functions of the nerve.
      Schwann cells are responsible for action potential velocity through insulation of
      axons, maintenance of axonal caliber, and correct localization of Na+ channels;
      immunological and funcitonal integrity of the nerve through the perineurial blood
      nerve-barrier; and effective nerve regeneration. In diabetic neuropathy, many of
      these facets of nerve function are defective. Hypoxia, hyerglycemia, and
      increased oxidative stress contribute directly and indirectly to Schwann cell
      dysfunction. The results include impaired paranodal barrier function, damaged
      myelin, reduced antioxidative capacity, and decreased neurotrophic support for
      axons. This chapter discusses the role of the Schwann cell in the normal or
      regenerating nerve nad in the altered metabolic conditons of diabetes.

PMID- 12198815
TI  - How does glucose generate oxidative stress in peripheral nerve?
AB  - Diabetes-associated oxidative stress is clearly manifest in peripheral nerve,
      dorsal root, and sympathetic ganglia of the peripheral nervous system and
      endothelial cells and is implicated in nerve blood flow and conduction deficits,
      impaired neurotrophic support, changes in signal transduction and metabolism, and
      morphological abnormalities characteristic of peripheral diabetic neuropathy
      (diabetic peripheral neuropathy). Hyperglycemia has a key role in oxidative
      stress in diabetic nerve, whereas the contribution of other factors, such as
      endoneurial hypoxia, transition metal imbalance, and hyperlipidemia, has not been
      rigorously proven. It has been suggested that oxidative stress, particularly
      mitochondrial superoxide production, is responsible for sorbitol pathway
      hyperactivity, nonenzymatic glycation/glycooxidation, and activation of protein
      kinase C. However, this concept is not supported by in vivo studies demonstrating
      the lack of any inhibition of the sorbitol pathway activity in peripheral nerve,
      retina, and lens by antioxidants, including potent superoxide scavengers. Its has
      been also hypothesized that aldose reductase (AR) detoxifies lipid peroxidation
      products, and therefore, the enzyme inhibition in diabetes is detrimental rather
      than benefical. However, the role for AR in lipid peroxdation product metabolism
      has never been demonstrated in vivo, and the effects of aldose reductase
      inhibitors and antioxidants on diabetic peripheral neuropathy are unidirectional,
      i.e., both classes of agents prevent and correct functional, metabolic,
      neurotrophic, and morphological changes in diabetic nerve. Growing evidence
      indicates that AR has a key role in oxidative stress in the peripheral nerve and
      contributes to superoxide production by the vascular endothelium. The potential
      mechanisms of this phenonmenon are discussed.

PMID- 12198816
TI  - Polyol pathway and diabetic peripheral neuropathy.
AB  - This chapter critically examines the concept of the polyol pathway and how it
      relates to the pathogenesis of diabetic peripheral neuropathy. The two enzymes of
      the polyol pathway, aldose reductase and sorbitol dehydrogenase, are reviewed.
      The structure, biochemistry, physiological role, tissue distribution, and
      localization in peripheral nerve of each enzyme are summarized, along with
      current informaiton about the location and structure of their genes, their
      alleles, and the possible links of each enzyme and its alleles to diabetic
      neuropathy. Inhibitors of pathway enzyme and results obtained to date with
      pathway inhibitors in experimental models and human neuropathy trials are updated
      and discussed. Experimental and clinical data are analyzed in the context of a
      newly developed metabolic odel of the in vivo relationship between nerve sorbitol
      concentration and metabolic flux through aldose reuctase. Overall, the data will
      be interpreted as supporting the hypothesis that metabolic flux through the
      polyol pathway, rather than nerve concentration of sorbitol, is the predominant
      polyol pathway-linked pathogeneic factor in diabetic preipheral nerve. Finally,
      key questions and future directions for bsic and clinical research in this area
      are considered. It is concluded that robust inhibition of metabolic flux through
      the polyol pathway in peripheral nerve will likely result in substantial clinical
      benefit in treating and preventing the currently intractable condition of
      diabetic peripheral neuropathy. To accomplish this, it is imperative to develop
      and test a new generation of "super-potent" polyol pathway inhibitors.

PMID- 12198818
TI  - Nerve growth factor for the treatment of diabetic neuropathy: what went wrong,
      what went right, and what does the future hold?
AB  - Since their discovery in the 1950s, neurotrophic factors have raised expectations
      that their clinical application to neurodegenerative diseases might provide an
      effective therapy for what are now untreatable conditions. Nerve growth factor
      (NGF) was the first neurotrophic factor to be discovered and was one of the
      earliest to proceed to clinical trials. NGF, which is selectively trophic for
      small fiber sensory and sympathetic neurons, was selected as a potential theraphy
      for diabetic polyneuropathy becaus of the serious consequences associated with
      degeneration of those neuronal populations in this condition. In addition,
      evidence shows that reduced availability of NGF may contribute to the
      pathogenesis of diabetic neuropathy, and animal models of neuropathy respond to
      the exogenous administration of NGF. Two sets of phase II clinical trails
      suggested that recombinant human NGF (rhNGF) administration was effective at
      ameliorating the symptoms associated with both diabetic polyneuropathy and HIV
      related neuropathy. These early studies,  however, revealed that painful side
      effects were dose limiting for NGF. A large-scale phase III clinical trail of
      1019 patients randomized to receive either rhNGF or palcebo for 48 weeks failed
      to confirm the earlier indications of efficacy. Among the explanations offered
      for the discrepancy between the two sets of trails was a robust palcebo effect,
      inadequate dosage, different study populatioms, and changes to the formulation of
      rhNGF for the phase III trail. As a  result of the phase III outcome, Genentech
      has decided not to proceed with further development of  rhNGF.

PMID- 12198817
TI  - Glycation in diabetic neuropathy: characteristics, consequences, causes, and
      therapeutic options.
AB  - Glycation is the nonenzymatic reaction of glucose, alpha-oxoaldehydes, and other
      saccharide derivatives with proteins, nucleotides, and lipids. Early glycation
      adducts (fructosamines) and advanced glycation adducts (AGEs) are formed.
      "Glycoxidation" is a term used for glycation processes involving oxidation.
      Sural, peroneal, and saphenous nerves of human diabetic subjects contained AGEs
      in the perineurium, endothelial cells, and pericytes of endoneurial microvessels
      and in myelinated and unmyelinated fibres localized to irregular aggregates in
      the cytoplasm and interstitial collagen and basement membranes. Pentosidine
      content was increased in cytoskeletal and myelin protein extracts of the sural
      nerve of human subjects and cytoskeletal proteins of the sciatic nerve of
      streptozotocin-induced diabetic rats. AGEs in the sciatic nerve of diabetic rats
      were decreased by islet transplantation. Improved glycemic control of diabetic
      patients may be expected to decrease protein glycation in the nerve. Protein
      glycation may decrease cytoskeletal assembly, induce protein aggregation, and
      provide ligands for cells surface receptors. The receptor for advanced glycation
      and products (RAGE) was expressed in peripheral neurons. It is probable that high
      intracellular glucose concentration is an important trigger for increased
      glycation, leading to increased formation of methylglyoxal, glyoxal, and 3
      deoxyglucosone that glycate proteins to form AGEs intracellularly and
      extracellularly. Oxidative stress enhances these processes and is, in turn,
      enhanced by AGE/RAGE interactions. An established therapeutic strategy to prevent
      glycation is the use of alpha-oxoaldehyde scavengers. Available therapeutic
      options for trial are high-dose nicotinamide and thiamine therapies to prevent
      methylglyoxal formation. Future possible therapeutic strategies are RAGE
      antagonists and inducers of the enzymatic antiglycation defense. More research is
      required to understand the role of glycation in the development of diabetic
      neuropathy.

PMID- 12198819
TI  - Angiotensin-converting enzyme inhibitors: are there credible mechanisms for
      beneficial effects in diabetic neuropathy?

PMID- 12198820
TI  - Clinical trials for drugs against diabetic neuropathy: can we combine scientific
      needs with clinical practicalities?
AB  - Diabetic neuropathy is a chronic progressive disease accounting for considerable
      morbidity and reduced quality of life among patients with diabetes. Accumulating
      evidence suggests that the clinical and neurophysiological markers used to assess
      neuropathy not only predict the development of neuropathic foot ulceration, one
      of the most common causes for hospital admission and lower limb amputations, but
      are also predictors of increased mortality in diabetic patients. In addition to
      metabolic control, drug treatment of both incipient and clinically manifest
      diabetic neuropathy will be necessary for the years to come. Because 1-2% of the
      whole population in western societies may be affected, the search for effective
      drug treatment  is not only a very important goal for the patient suffering from
      diabetic neuropathy and for the practicing physician, but also an  economic task
      for both the health care systems and pharmaceutical companies. The validity of
      inferences about the clinical consequences of the use of any given agent to
      induce a specific pharmacologic effect will depend not only on the extent to
      which it affects the targeted biological phenomenon, but also on the extent to
      which all of the actions of the agent have been defined and the extent to which
      all affect the entire organism, alone and in concert.  The ultimate test of the
      usefulness of a drug or device depends on the determination of outcomes, ideally
      in randomized clinical trials (RCTs) of sufficient scope and duration. The
      efficacy and safety of a variety of drugs based on the different pathogenetic
      hypotheses proposed have been evaluated in RCTs since the 1970s. However, the
      quality of RCTs published between 1981 and 1992 that evaluated the effects of
      medical treatment in diabetic polneuropathy was poor. Adequate designs for RCTs
      in diabetic neuropathy must consider the following criteria: type and stage of 
      neuropathy, homogeneity of the study population, outcome measures
      (neurophysiological markers, intermediate clinical end points, ultimate clinical
      outcomes, quality of life), natural history, sample size, study duration,
      reproducibility of neurophysiological and intermediate end points, nonspecific
      effects of treatment, measures of treatment effect, the extent to which the
      overall trail result applies to individual patients (external validity), and the
      reporting of the RCTs. Trials focusing preferentially on patients with mild or
      moderate early stages of neuropathy over long periods of  3-5 years aimed at
      slowing or prevention, rather than reversal, using end point measures that have
      clinical and prognostic significance are most likely to produce meaningful
      results.

PMID- 12198821
TI  - Protein kinase C changes in diabetes: is the concept relevant to neuropathy?
AB  - Protein kinase C (PKC) comprises a superfamily of isoenzymes, many of which are
      activated by 1,2-diacylglycerol (DAG) in the presence of phosphatidylserine. In
      order to be capable of DAG activation, PKC must first undergo a series of
      phosphorylation at three conserved sites. PKC isoforms phosphorylate a wide
      variety of intracellular target proteins and have multiple functions in signal
      transduction-mediated cellular regulation. An elevation in DAG levels and an
      increase in composite PKC activity and/or certain isoforms occurs in several
      nonneural tissues from diabetic animals, including the vasculature. The ability
      of isoform-specific PKC inhibitors to antagonize diabetes-induced abnormalities
      has implicated altered PKC beta activity in the onset of several diabetic
      complications, In contrast to many other tissues, DAG levels fall in diabetic
      nerve and a consistent pattern of change in PKC activity has not been observed.
      Treatments that alter PKC activity affect nerve Na+, K+-ATPase activity, but the
      mechanism involved is not well understood, Inhibition of PKC beta in diabetic
      rats appears to correct reduced nerve blood flow and decreased nerve conduction
      velocity. These and other findings indicate that changes in the neurovasculature
      exert adverse effects during the pathogenesis of diabetic neuropathy. Still
      unresolved is a clear-cut role for PKC in the development of abnormalities in
      neural cell metabolism. Further progress will depend on a more complete
      understanding of the functions of individual PKC isoforms in nerve. Future
      investigation could focus profitably on biochemical processes in nerve cells that
      modulate PKC activity and that are altered in diabetes, such as vascular
      endothelial growth factor levels and production of reactive oxygen species
      arising from oxidative stress.

PMID- 12198822
TI  - Are mitogen-activated protein kinases glucose transducers for diabetic
      neuropathies?

PMID- 12198823
TI  - [Acute appendicitis in children: serious complications when treatment is
      delayed].
AB  - Three children, two boys aged 9 and 6 and a 12-year-old girl, had diffuse
      abdominal complaints, diarrhoea and a (sub)febrile temperature for several days.
      On admission, they were found to have a perforated inflamed appendix and
      peritonitis. Following asystole, intra-abdominal abscesses and an enterocutaneous
      fistula, the oldest boy showed good recovery after a hospital stay of two months;
      the girl recovered after one month in hospital following a psoas muscle abscess
      and two episodes of constrictive pericarditis with threatened tamponade. The
      younger boy was dead on arrival at the hospital. Appendicitis is not always easy
      to diagnose. An atypical presentation, very often with diarrhoea, can result in
      diagnostic delay. Early surgical consultation is mandatory in a child with
      progressive abdominal pain.

PMID- 12198824
TI  - [An analysis of cases of missed acute appendicitis: for the time being there is
      no basis for a better policy].
AB  - Case reports of patients with acute appendicitis that was not recognised in time
      highlight the probability and the implications of significant complications.
      Early surgical treatment is dependent on early diagnosis, and this is usually the
      domain of general practice. With regard to the missed cases, it is important to
      see them in proper perspective: appendicitis is present in only a minority of all
      presentations of abdominal pain. General practitioners should refer 'liberally'
      in case of even minor signs or symptoms, so that appendicitis will be missed only
      in cases with a highly atypical presentation. It is important to realise that
      this happens, but it is not possible to draw conclusions from it that can serve
      as a guide to routine practice, as referral of all presentations of abdominal
      pain would be undesirable. There is a need to test the added value of diagnostic
      procedures like CRP and echography. However, until there is evidence that this
      could change the practice in atypical cases, practitioners can do no better than
      to reflect upon their faults.

PMID- 12198825
TI  - ['Survival of the fittest': effect of regular physical exercise on health and
      life expectancy].
AB  - According to the 'Australian burden of disease study', physical inactivity
      appears to be a leading risk factor in the population at large, accounting for no
      less than 6.7% of the total loss of disability-adjusted life years. In women it
      is even the most important risk factor. Regular physical mobility and exercise
      can reduce this negative influence. The effects are: improvement of
      cardiovascular fitness, prevention of coronary events, and the reduction of
      excess mortality. The mortality risk may be reduced by 47% by physical activity,
      depending on the energy expenditure. Especially the studies of the last two years
      have so convincingly proven a robust effect of daily physical exercise that on
      this point permissiveness is no longer acceptable in the advice to the population
      at large.

PMID- 12198826
TI  - [Acute cardiovascular complications of vigorous physical exertion by untrained
      persons].
AB  - Physical exertion has paradoxical effects: regular physical activity offers
      protection against cardiovascular diseases, but, on the other hand, it has been
      shown that strenuous exercise can provoke coronary heart disease and sudden
      death. The risks of vigorous exertion apply particularly to untrained individuals
      and persons with a sedentary lifestyle. Physical exertion can cause a myocardial
      infarction or sudden death in people who were considered perfectly healthy before
      this event. In most cases, the mechanism of this is probably a rupture at the
      site of a vulnerable atherosclerotic plaque, with local activation of
      coagulation. Disturbances in cardiac rhythm may also be a cause of these
      complications.

PMID- 12198827
TI  - [From gene to disease; unconjugated hyperbilirubinemia: Gilbert's syndrome and
      Crigler-Najjar types I and II].
AB  - Gilbert's syndrome consists of a mild unconjugated hyperbilirubinemia occurring
      in the absence of liver disease or haemolysis. Total plasma bilirubin can be as
      high as 80 mumol/l and mild intermittent jaundice does occur. The inheritance
      pattern is probably autosomal recessive. It has been estimated that some 10-15%
      of the Western population suffers from Gilbert's syndrome. Bilirubin
      uridinediphosphate-glucuronosyltransferase (UGT1A1) is the only enzyme involved
      in the conjugation of bilirubin. In patients with Gilbert's syndrome, hepatic
      glucuronidation by UGT1A1 is reduced to about 30% of normal. In Western
      populations a variant TATAA element in the upstream promotor region of the UGT1A1
      gene is firmly associated with the disease. Crigler-Najjar types I and II are
      autosomal recessive disorders associated with near (type II) or complete absence
      (type I) of UGT1A1 enzyme activity. There is a persistent unconjugated
      hyperbilirubinemia (range 300-850 mumol/l) with the plasma concentrations being
      higher in type I than in type II. Genetic mutations in exon 1-5 cause both
      Crigler-Najjar type I and type II.

PMID- 12198828
TI  - [Diagnostic image (100). A man with migrating joint complaints. Tophaceous gout].
AB  - An 80-year-old man using diuretics for chronic cardiac failure was diagnosed with
      tophaceous gout.

PMID- 12198829
TI  - [Acute respiratory distress syndrome more frequently diagnosed in intensive care
      patients in the Netherlands than would occur according to internationally
      established criteria].
AB  - OBJECTIVE: To determine the agreement of the diagnosis 'acute respiratory
      distress syndrome' (ARDS) established by intensive care (IC) specialists, with
      that according to internationally accepted objective criteria. DESIGN:
      Descriptive inventory. METHOD: All 119 hospitals in the Netherlands with an IC
      department were asked to participate; 34 did (29%). On 3 consecutive days, IC
      specialists completed a case-record form concerning the respiratory status and
      additional treatment of all of their patients. In the case of mechanical
      ventilation, the specialist could indicate whether ARDS or another condition was
      the cause of the respiratory insufficiency. In addition to this, objective data
      were requested so that the investigators could establish whether there was ARDS
      on the basis of the North American-European Consensus Conference (NAECC) criteria
      and the less generally accepted 'Lung injury score' (LIS > or = 2.5). RESULTS: Of
      the 266 patients about whom a case record form was returned, 151 were
      mechanically ventilated. ARDS was diagnosed in 36 of these patients according to
      the IC specialists, in 24 according to the NAECC and in 20 according to the LIS
      criteria (p < 0.05 versus IC specialists). The chance-corrected agreement (kappa)
      between the diagnoses by IC specialists and the NAECC criteria was 0.34 (p <
      0.001) and between the IC specialists and the LIS 0.44 (p < 0.001). The kappa
      between the NAECC and the LIS diagnoses was 0.42 (p < 0.001). Using NAECC and/or
      LIS criteria as the golden standard, a correct ARDS diagnosis was made by the IC
      specialists in the case of 20 patients, a false-positive diagnosis in the case of
      16 patients and a false-negative diagnosis in the case of 13 patients.
      CONCLUSION: In this investigation, the diagnosis of ARDS was more frequently
      established than would occur according to the NAECC criteria.

PMID- 12198830
TI  - [Intestinal parasites in African asylum seekers: prevalence and risk factors].
AB  - OBJECTIVE: To determine the prevalence of potentially pathogenic intestinal
      parasites in asylum seekers coming from a highly endemic area, and to identify
      groups of asylum seekers from Africa with a high risk of an intestinal parasitic
      infestation which is potentially harmful of their own health or that of those in
      their vicinity. DESIGN: Prospective. METHOD: In the period January 1996-May 1999,
      956 asylum seekers from Africa were checked for intestinal parasites by means of
      a stool examination within one month of arriving in the Netherlands. Independent
      variables for data analysis were sex, age and area of origin. RESULTS: Pathogenic
      intestinal parasites were found in 40.6% of the 956 African asylum seekers coming
      from areas south and east of the Sahara. Double-infection was found in 9.5% and
      triple-infection in 0.9% of the study population. The most common pathogenic
      parasite was Trichuris trichiura (13.6%) followed by Entamoeba histolytica/dispar
      (8.8%), hookworms (7.8%), Schistosoma (7.0%) and Giardia lamblia (5.0%). G.
      lamblia was the most commonly found potentially pathogenic parasite in children
      less than 13 years old (19.0%). In the population from Western Africa, 15.6% had
      a hookworm and 12.8% a Schistosoma. Both these helminthic infestations were three
      times as prevalent in men as in women. CONCLUSION: Sex, age and area of origin
      were important indicators for the species of parasite. On the basis of this, risk
      groups can be selected for screening for potentially pathogenic intestinal
      parasites.

PMID- 12198831
TI  - [Prolonged diarrhea and weight loss after a biking trip from Tibet to Nepal:
      infection with Cyclospora].
AB  - A 39-year-old man, who had made a cycling tour from Tibet to Nepal, visited the
      outpatients' clinic one month later because of prolonged diarrhoea, abdominal
      complaints and serious weight loss. Parasitological examination of the stool
      revealed oocysts of Cyclospora cayetanensis and the patient was treated with
      trimethoprim-sulfamethoxazole (co-trimoxazole) with good result. C. cayetanensis
      has only recently been discovered as a protozoal cause of diarrhoea. Infections
      are primarily reported from areas with a low hygienic standard e.g. Central and
      South America, the Indian subcontinent (Nepal), Indonesia and South-East Asia.
      Clinical symptoms of infection are diarrhoea (usually watery), abdominal cramps
      and discomfort. The infection can have a prolonged course. Diagnosis is made by
      parasitological examination of the stool (one should be cautious not to confuse
      with cryptosporidia) and treatment with trimethoprim-sulfamethoxazole is
      effective.

PMID- 12198832
TI  - [The relationship between asthma and chronic obstructive and restrictive
      pulmonary diseases; lessons from the past century].
AB  - The so-called 'Dutch hypothesis' (Fletcher) which describes chronic obstructive
      (restrictive) pulmonary disease (CO(R)PD) as a consequence of complicated
      childhood asthma (from 1900-1960) is well-founded. It can explain many aspects of
      the ever changing pattern of asthma and COPD in the Western world. Severe
      respiratory disease in children during the first part of the 20th century was
      primarily the result of respiratory complications of measles and whooping cough,
      and caused a high mortality in children below the age of two years. Gradually
      more children survived and a picture of the complications was formed: chronic
      bronchitis and bronchiectasis. In 1939 it was suggested that this happened mainly
      in children with asthmatic predisposition and this pattern was documented in
      detail in the post World War II period. After 1970 the complications virtually
      disappeared as a result of vaccination and improved therapy. Consequently,
      bronchiectasis and cor pulmonale became rare and CO(R)PD became COPD, the old-age
      form of asthma. There has also been a marked increase in asthma after childhood
      over the past 30 years. The double role of obstruction-provoking and anti
      obstructive (and asthma-masking) infections plays an important role in this
      respect. The old picture from the fifties in the Western world still prevails in
      developing countries. Prevention of this 'old COPD' must consist of vaccination
      against measles and whooping cough (and possibly also against respiratory
      syncytial virus), and treatment of asthma.

PMID- 12198833
TI  - [One hundred years of the Netherlands Association of Surgeons. I. Introduction].

PMID- 12198834
TI  - [The Dutch College of General Practitioners' 'Irritable bowel syndrome'
      standard].

PMID- 12198835
TI  - [The Dutch College of General Practitioners' 'Irritable bowel syndrome'
      standard].

PMID- 12198836
TI  - [Pilot study of hypovitaminosis D in apparently healthy veiled Turkish women:
      severe vitamin D deficiency in 82%].

PMID- 12198837
TI  - Continuous permeation of analytes through a thin poly(dimethylsiloxane) membrane
      followed by sorbent trapping for their gas chromatographic monitoring.
AB  - Parameters that affect the permeation of analytes across a thin (0.025 mm) flat
      membrane of polysiloxane in a membrane and trap interface coupled to a gas
      chromatograph are examined taking into account a mechanism of mass transport for
      porous and nonporous materials and the permeation of carrier gas in the direction
      opposite to that of the analytes. The best permeation rate was reached with
      hydrogen as carrier gas at a flow-rate between 3 and 5 ml/min, an agitation of
      analytes outside the membrane above 0.4 m/s and thin membrane. The parameters
      that affect the residual diffusion time of analytes in membrane were also
      examined. A practical application of the thin membrane in membrane and trap
      interface was demonstrated by gas chromatographic monitoring of six volatile
      organic compounds in air. The limit of detection is at the nmol/ml level
      depending on the time of trapping and the parameters that affect the permeation
      through the membrane.

PMID- 12198838
TI  - Dynamic microwave-assisted extraction coupled on-line with solid-phase
      extraction: determination of polycyclic aromatic hydrocarbons in sediment and
      soil.
AB  - This paper describes a new extraction tool for the determination of polycyclic
      aromatic hydrocarbons (PAHs) in soil and sediment samples, using dynamic
      microwave-assisted extraction combined with solid-phase extraction (DMAE-SPE).
      The critical variables for DMAE-SPE are investigated and optimized in an
      experimental design. The technique proved to be fast, accurate and able to yield
      quantitative extraction of PAHs from naturally contaminated sediment and soil
      samples. The set-up is fully automated and features monitored extraction, which
      facilitates rapid optimization of the method. In addition, only small quantities
      of solvent and sample are required.

PMID- 12198839
TI  - Retention of alkali, alkaline earth and transition metals on an itaconic acid
      cation-exchange column. Eluent pH, ionic strength and temperature effects upon
      selectivity.
AB  - The unusual selectivity of a methylene succinic (itaconic) acid modified
      polymeric column was investigated for the separation of alkali, alkaline earth,
      transition and heavy metals employing non-chelating inorganic eluents. The
      retention of selected metal ions on the column was investigated with simple HNO3
      eluents and eluents prepared from KNO3 and KCl salts of varying pH (adjusted
      using HNO3). From these studies both the effect of eluent ionic strength and pH
      upon retention was evaluated for the itaconic acid stationary phase. The results
      obtained showed that despite slow exchange kinetics causing poor efficiencies,
      acceptable baseline separations of selected alkaline earth and transitions could
      be obtained under optimum conditions (the baseline separation of Mg(II), Ca(II),
      Mn(II), Cd(II), Zn(II) and Co(II) was possible using a 15 mM KNO3-5 mM KCl eluent
      at pH 3.50 in under 25 min). The use of an simple ionic strength step gradient
      was shown that facilitated the addition of Pb(II) to the above group of metal
      ions. An investigation into the effect of temperature upon peak efficiency and
      retention showed increased column temperature could be used to improve the
      resolution of closely eluting metal ions such as Ca(II) and Sr(II) and Ca(II) and
      Mn(II).

PMID- 12198840
TI  - Preparative isolation of polyphenolic compounds from Vitis vinifera by
      centrifugal partition chromatography.
AB  - This study deals with a centrifugal partition chromatography developed for the
      separation of phenolic compounds from Vitis vinifera. EtOAc grape seed extracts
      were separated using the solvent system hexane-ethyl acetate-ethanol-water
      (1:8:2:7; v/v) in two fractions: one containing about 75% of flavanol monomers
      (catechin and epicatechin) corresponding to 18% of crude extract and another
      fraction B-type dimers (22% of crude extract). From the stalk extracts, we could
      separate stilbenoid compounds (resveratrol and its oligomers; 12% of crude
      extract) which were eluted in less than 30 min from flavanols (which required a
      few hours of additional elution). Using the same solvent system but in different
      ratios (4:5:3:3; v/v), we isolated the trans-resveratrol (7@1000; 90% purity).

PMID- 12198841
TI  - Simple method for reversed-phase high-performance liquid chromatographic analysis
      of fungal pigments in fruit-bodies of Boletales (Fungi).
AB  - A reversed-phase HPLC method has been developed for the analysis of hydroxylated
      pulvinic acid derivatives which are responsible for the pigmentation of fruit
      bodies belonging to the order Boletales (Fungi). Variegatic, xerocomic and
      atromentic acid as well as variegatorubin were detected and separated in
      methanolic extracts of Boletus permagnificus and Xerocomus parasiticus, and the
      pigment profile of these species was compared. The identity of the pigments was
      confirmed by means of LC-atmospheric pressure chemical ionization (APCI) mass
      spectrometry.

PMID- 12198842
TI  - Analysis of ergosteroids. VIII: Enhancement of signal response of neutral
      steroidal compounds in liquid chromatographic-electrospray ionization mass
      spectrometric analysis by mobile phase additives.
AB  - The signal response of moderately polar to nonpolar neutral steroidal compounds
      in positive ion mode was significantly improved in electrospray ionization mode
      by addition of volatile organic acids (trifluoroacetic acid, acetic and formic)
      at concentrations much lower than those normally employed for high-performance
      liquid chromatographic separations of ionic compounds. Each of the three acids
      enhanced the sensitivity, the order being: formic acid (approximately 50-200 ppm,
      v/v) > acetic acid (100-500 ppm) > trifluoroacetic acid (5-20 ppm). Higher
      concentrations caused decrease in the sensitivity. The extent of increase in the
      sensitivity was compound specific and also depended on the nature of organic
      modifier present in the mobile phase. Acetic acid was the acid of choice for the
      'wrong-way-round' ionization of sulfate conjugates. The postcolumn addition of
      silver nitrate produced highly stable (M + Ag)+ adducts with concomitant increase
      in signal response and reduction in baseline noise.

PMID- 12198843
TI  - Method based on solid-phase microextraction--high-performance liquid
      chromatography with UV and electrochemical detection to determine estrogenic
      compounds in water samples.
AB  - We determined a group of estrogenic compounds by solid-phase microextraction
      (SPME) coupled to high-performance liquid chromatography (HPLC) with both
      ultraviolet (UV) and electrochemical detection (ED). A modified liquid
      chromatograph was used. Polyacrylate fibers (85 microns) were used to extract the
      analytes from the aqueous samples. Dynamic and static modes of desorption were
      compared and the variables affecting both absorption and desorption processes in
      SPME-HPLC were optimized. Static desorption gave the best recoveries and peak
      shapes. The performance of the SPME-HPLC-UV-ED method was checked with river
      water and wastewater. The method enabled estrogenic compounds to be determined at
      low-microgram l-1 levels in real water samples. Limits of detection were between
      0.3 and 1.1 micrograms l-1 using UV detection and between 0.06 and 0.08 microgram
      l-1 using ED. beta-Estradiol was found in samples from a wastewater treatment
      plant at concentrations between 1.9 and 2.2 micrograms l-1.

PMID- 12198844
TI  - Determination of chiral sulfoxides in plasma by normal-phase liquid
      chromatography-atmospheric pressure chemical ionization mass spectrometry.
AB  - A sensitive and specific assay has been developed and validated for the
      separation of a chiral sulfoxide drug candidate with simultaneous determination
      of the corresponding sulfide and sulfone in plasma by normal-phase LC-MS-MS.
      Separation was achieved on a Chiralpak AD (100 x 2.1 mm) column with a 2-propanol
      hexane (80:20) mobile phase within 7 min. Aqueous mobile phase (2-propanol-10 mM
      ammonium acetate, 75:25) was added post-column prior to introduction into the
      heated nebulizer interface of a Sciex API 3 plus mass spectrometer, to avoid the
      explosion hazard of hexane-containing mobile phases in the presence of a corona
      discharge. The linear range of this assay was 5-2500 ng/ml. The accuracy and
      precision of the chiral sulfoxides, the sulfide and the sulfone were within +/-
      15% across the linear range. The limit of quantitation for each component was 5
      ng/ml based on the extraction of 0.25 ml plasma. The recovery for each component
      was between 82 and 120%. This assay was sufficiently sensitive and specific to
      support pre-clinical development studies in rats, dogs and monkeys.

PMID- 12198845
TI  - Size-exclusion chromatography in 1,1,1,3,3,3-hexafluoro-2-propanol.
AB  - 1,1,1,3,3,3-Hexafluoroisopropanol is re-examined as an eluent for size-exclusion
      chromatography (SEC) of polyesters, nylons, and other polar polymers. It is shown
      that anomalous SEC behavior reported in previous literature can be eliminated by
      adding 0.01 M tetraethylammonium nitrate to the eluent. The eluent modifier does
      not affect the solution viscosity or root-mean-square radii of moderately polar
      polymers such as polyesters and nylons, but it does decrease these quantities for
      more polar polymers such as poly(ethylene oxide) and poly(2-vinylpyridine). More
      important, this salt appears to minimize repulsive interactions with styrene
      divinylbenzene column packings that have contributed to non-ideal size-exclusion
      behavior. As a result, conditions are established that satisfy universal
      calibration.

PMID- 12198846
TI  - Effect of the counter-anion type and concentration on the liquid chromatography
      retention of beta-blockers.
AB  - Analysis of beta-blockers, basic pharmaceutical compounds with pKa values greater
      than 8.5, in reversed-phase HPLC can sometimes be challenging in terms of
      selection of the mobile phase pH, buffer concentration, and acidic modifier. The
      effect of the type and concentration of various mobile phase additives on the
      reversed-phase HPLC retention of these compounds was studied. HPLC analysis was
      performed at a mobile phase pH of 3 ensuring the protonation of the beta
      blockers. It was found that at increasing perchlorate anion concentration at a
      constant mobile phase pH the retention factor for all beta-blocker compounds
      studied increased to varying degrees. The relative increase in the retention was
      attributed to ion interaction with the anionic mobile phase additive. Similar
      trends were observed when other types of inorganic salts such as NaH2PO4, NaPF6,
      NaBF4, and CF3CO2Na were employed. Differences in selectivity of the beta
      blockers were obtained at a constant pH and an equimolar concentration of the
      different additives throughout the whole concentration range studied.

PMID- 12198847
TI  - Determination of Penicillium mycotoxins in foods and feeds using liquid
      chromatography-mass spectrometry.
AB  - New LC-MS (full scan) and LC-MS-MS (selected ion reaction monitoring) methods for
      the simultaneous determination of mycophenolic acid, griseofulvin, roquefortine
      C, chaetoglobosin B, verruculogen and penitrem A, and other Penicillium derived
      mycotoxins in food and feed samples are described. The methodologies involve
      sample extraction with acetonitrile-water, defatting with hexane and
      quantification using LC-MS with atmospheric pressure chemical ionisation or LC-MS
      MS. Detector responses, for each of the methods and mycotoxins, were found to be
      linear over the range 10-1000 ng of mycotoxin/g of extracted food mixture
      material. The mean recoveries (n = 3 to 6) of the mycotoxins from spiked food
      mixture samples determined using MS and MS-MS detection were 87-116 and 91-112%,
      respectively, for mycophenolic acid, 104-109 and 91-112%, respectively, for
      griseofulvin, 70-85 and 75-110%, respectively, for roquefortine C, 94-109 and 81
      116%, respectively, for chaetoglobosin B, 110-115 and 90-106%, respectively, for
      verruculogen and 78-97 and 99-108%, respectively, for penitrem A. RSDs varied
      from 5.6% at the 1000 ng/g level to 23.1% at the 10 ng/g level. The limits of
      detection for the mycotoxins using MS and MS-MS were 70 and 10 ng/g,
      respectively, for mycophenolic acid, 10 and 5 ng/g, respectivley, for
      griseofulvin, 50 and 20 ng/g, respectively, for roquefortine C, 25 and 20 ng/g,
      respectively, for chaetoglobosin B, 25 and 20 ng/g, respectively, for
      verruculogen and 10 and 5 ng/g, respectively, for penitrem A.

PMID- 12198848
TI  - Inverse gas chromatographic measurement of solubility parameters in liquid
      crystalline systems.
AB  - Inverse gas chromatography, (IGC), has been used to measure interaction
      parameters in two low-molar-mass liquid crystals and a polymer substituted with
      the same mesogenic group. Solubility parameters have been calculated. The IGC
      method is shown to be applicable to this class of compounds and to give
      meaningful values over a range of temperatures.

PMID- 12198849
TI  - Determination of pyrethroid residues in tobacco and cigarette smoke by capillary
      gas chromatography.
AB  - The extraction of fenpropathrin, cyhalothrin, cypermethrin, fenvalerate and
      deltamethrin from tobacco (Nicotina tobaccum) and cigarette smoke condensate with
      acetone, followed by partition of resulting acetone mixture with petroleum ether,
      was investigated and found suitable for capillary gas chromatography (GC) residue
      analysis. Florisil column clean-up was found to provide clean-up procedure for
      tobacco and cigarette smoke condensate permitting analysis to < or = 0.01
      microgram.g-1 for most of the pyrethroids by GC with a 63Ni electron capture
      detector (GC-ECD). Quantitative determination was obtained by the method of
      external standards. Cigarettes made from flue-cured tobacco spiked with different
      amounts of pyrethroids were used and the pyrethroid levels in mainstream smoke
      were determined. For all the pyrethroid residues, 1.51-15.50% were transferred
      from tobacco into cigarette smoke.

PMID- 12198850
TI  - Determination of organochlorine pesticides in ground water using solid-phase
      microextraction followed by dual-column gas chromatography with electron-capture
      detection.
AB  - A rapid, sensitive, convenient, and highly quality-assured method is presented
      for the determination of 19 organochlorine pesticides (OCPs) in small samples (10
      ml) of ground water. Samples are initially fortified with 2,4,5,6-tetrachloro-m
      xylene (surrogate) and decachlorobiphenyl (retention time marker), then extracted
      with a 30-micron thickness polydimethylsiloxane solid-phase microextraction
      fiber. The analytes collected are thermally desorbed in a heated gas
      chromatographic inlet, separated using independent fused-silica capillary columns
      ("primary" and "confirmatory"), and detected using electron-capture detection.
      Two independent statistical procedures were used to evaluate the detection
      limits, which typically range between 10 and 40 ng l-1, for these analytes.
      Method performance was also evaluated using two additional protocols employing
      "performance evaluation" samples, in which authentic ground water samples were
      fortified to ca. 100 ng l-1 in each of at least six OCPs. The method satisfies
      additional strict criteria based on uniformity of fiber performance and minimal
      degradation of the thermally-sensitive analytes endrin and DDT.

PMID- 12198851
TI  - Capillary electrophoresis in aqueous-organic media. Ionic strength effects and
      limitations of the Hubbard-Onsager dielectric friction model.
AB  - The mobilities of three aromatic sulfonates, ranging in charge from -1 to -3,
      were investigated by capillary electrophoresis using buffers containing 0 to 75%
      ethanol or 2-propanol. Absolute mobilities were determined by extrapolation of
      the effective mobilities to zero ionic strength according to the Pitts' equation.
      For all buffers studied, ions of higher charge experienced larger ionic strength
      effects. The resulting ionic strength-induced selectivity alterations were more
      dramatic when organic solvents were present in the media. Furthermore, for
      different organic modifier types and contents, the magnitude of the ionic
      strength effect was governed to a large extent by the 1/(eta epsilon 1/2)
      dependence in the electrophoretic effect of the Pitts' equation. Addition of
      ethanol or 2-propanol to the electrophoretic media resulted in changes in the
      absolute mobilities of the ions. These solvent-induced mobility changes are
      attributed to dielectric friction. As predicted by the Hubbard-Onsager model,
      dielectric friction increased with increasing organic content and with increasing
      analyte charge. As a result, dramatic changes in the relative absolute mobilities
      were observed, such as a reversal in migration order between sulfonates of -1 and
      -3 charge in 75% 2-propanol. Within the alcohols, the Hubbard-Onsager model was
      successful at predicting the relative mobility trends upon changing solvent.
      However, the relative trends observed between acetonitrile-water and alcohol
      water media were not consistent with the model. This may be explained by the
      continuum nature of the model, whereby the different ion-solvent interactions
      characteristic to each solvent class are not taken into account.

PMID- 12198852
TI  - Application of a contactless conductometric detector for the simultaneous
      determination of small anions and cations by capillary electrophoresis with dual
      opposite end injection.
AB  - A contactless conductometric detection (CCD) system for capillary electrophoresis
      (CE) with a flexible detection cell was applied for the simultaneous
      determination of small anions and/or cations in rain, surface and drainage water
      samples. The applied frequency, the amplitude of the input signal, the
      electrolyte conductivity and electrode distance were found to be the most
      significant factors affecting the detection sensitivity. 2-(N
      Morpholino)ethanesulfonic acid/histidine-based (MES/His) electrolytes were used
      for direct conductivity detection of anions and cations, while ammonium acetate
      was selected for indirect conductivity determination of alkylammonium salts. For
      the simultaneous separation procedure, involving dual-opposite end injection, an
      electrolyte consisting of 20 mM MES/His, 1.5 mM 18-crown-6 and 20 microM
      cetyltrimethylammonium bromide provided baseline separation of 13 anions and
      cations in less than 6 min. The detection limits achieved were 7-30 micrograms/l
      for direct conductometric detection of various common inorganic cations and
      anions, excluding F- (62 micrograms/l) and H2PO4- (250 micrograms/l), and 35-178
      micrograms/l for indirect conductometric detection of alkyl ammonium cations. The
      developed electrophoretic method with conductometric detection was compared to
      ion chromatography.

PMID- 12198853
TI  - Use of capillary electrophoresis and laser-induced fluorescence for attomole
      detection of amino acids.
AB  - A capillary electrophoresis and laser-induced fluorescence (CE-LIF) method was
      developed to identify and quantitate at amol (10(-18)) concentration. Amino acids
      were derivatized with 3-(4-carboxybenzoyl)-2-quinoline-carboxaldehyde prior to CE
      LIF analysis. The assay was developed by varying the sodium borate concentration,
      buffer pH, operating voltage, and operating temperature. A run buffer system
      containing 6.25 mM borate, 150 mM sodium dodecyl sulfate, and 10 mM
      tetrahydrofuran (pH 9.66) at 25 degrees C, and 24 kV provided analysis conditions
      for a high-resolution, sensitive, and repeatable assay of amino acids. The rate
      of derivatization, stability of the labeled amino acids, and amino acid
      quantitation varied for each amino acid. Amino acids were detected with greater
      efficiency by this method than automated HPLC amino acid analysis. The
      repeatability of the assay ranged from 0.3 to 0.9% within a day and 0.7 to 1.5%
      between analysis days. Bacterial amino acid utilization in a chemically defined
      medium was successfully monitored using this method. This work defines a
      sensitive and repeatable method for the detection of amino acids during bacterial
      metabolism.

PMID- 12198854
TI  - Study on protein adsorption kinetics to a dye-ligand adsorbent by the pore
      diffusion model.
AB  - Adsorption kinetics of bovine serum albumin (BSA) and bovine hemoglobin (bHb) to
      Cibacron Blue 3GA (CB) modified Sepharose CL-6B has been studied. The effects of
      liquid-phase ionic strength and CB coupling density on the uptake rates of these
      two proteins in Tris-HCl buffer (pH 7.5) were evaluated by effective pore
      diffusivity derived from a pore diffusion model. The results showed that despite
      their similar molecular masses and sizes, the effects of aqueous-phase ionic
      strength and CB density on the effective pore diffusivities of BSA and bHb were
      distinctly different. The effective pore diffusivity of BSA to CB-Sepharose
      increased significantly with decreasing CB density and increasing liquid-phase
      ionic strength. This was considered due to the decrease in electrostatic
      repulsion between the BSA and CB molecules of like charge. That is, the increase
      in ionic strength and the decrease in CB coupling density reduced the
      electrostatic hindrance effect on BSA diffusion to CB-Sepharose, facilitating the
      hindered pore diffusion. In contrast, because of the higher isoelectric point of
      bHb (7.0) compared to BSA (4.7), bHb suffered little electrostatic hindrance
      effect during its diffusion to CB-Sepharose. Therefore, the effective pore
      diffusivity of bHb was unchanged with the change in liquid-phase ionic strength
      and CB coupling density.

PMID- 12198855
TI  - Enthalpic interactions in size exclusion chromatography of pullulan and cellulose
      in LiCL-N,N-dimethylacetamide.
AB  - Enthalpic phenomena were shown to contribute to the size exclusion separation
      mechanisms during chromatographic analysis of solutions of pullulan and cellulose
      in LiCl-N,N-dimethylacetamide (LiCl-DMAc) solvent and eluent. The effect of LiCl
      concentration in the sample solutions and the effect of temperature were of the
      same order of magnitude for both pullulan and cellulose samples. This led to
      systematic errors in the determination of mean molecular mass in the range of
      tens of percent, depending on the chromatographic conditions and on the molecular
      mass of the analyte. The systematic error is much higher than the random errors;
      the typical values of the latter being up to a few percent (RSD). Low column
      temperature and a higher content of LiCl in the sample solution led to lower
      determined mean molecular mass values. This can be explained by a decrease in the
      interactions between dissolved macromolecules, although polymer-stationary phase
      interactions should also be taken into account. Furthermore, the cellulose
      stability in solution was determined: the zero order random degradation constant
      being k = 6.9 x 10(-8) mol mol-1 monomer day-1.

PMID- 12198856
TI  - Retention of ionizable compounds in high-performance liquid chromatography. 14.
      Acid-base pK values in acetonitrile-water mobile phases.
AB  - Linear relationships between sspKa values in acetonitrile-water mixtures and
      wwpKa values in pure water have been established for five families of compounds:
      aliphatic carboxylic acids, aromatic carboxylic acids, phenols, amines, and
      pyridines. The parameters (slope and intercept) of the linear correlations have
      been related with acetonitrile-water composition. The proposed equations allow
      accurate estimation of the pKa values of any member of the studied families at
      any acetonitrile-water composition up to 60% of acetonitrile in volume (100% for
      pyridines). Conversely, the same equations can be used to estimate aqueous pKa
      values from chromatographic pKa values obtained from any acetonitrile-water
      mobile phase between the composition range studied. Estimation of pKa values have
      been tested with chromatographic literature data.

PMID- 12198857
TI  - Characterisation of reversed-phase stationary phases for the liquid
      chromatographic analysis of basic pharmaceuticals by thermodynamic data.
AB  - This paper describes the characterisation of reversed-phase liquid chromatography
      (RPLC) columns using thermodynamic measurements. Retention versus 1/T data were
      used to construct Van't Hoff plots. The slope of these plots indicates the
      standard enthalpy of transfer of the analyte from the mobile to the stationary
      phase. The standard entropy can be calculated from the intercept. Van't Hoff
      plots were linear for the investigated RPLC columns, meaning that for basic
      analytes over the temperature range studied no changes in the retention mechanism
      occurred. Enthalpies and entropies of transfer of basic analytes from the mobile
      to the stationary phase revealed information about the types of interaction of
      protonated and neutral compounds with the stationary phases. However, a clear
      view using the present set of basic compounds on how these thermodynamic data may
      explain the observed substantial differences in peak symmetry cannot be given. It
      is considered that addition of N,N-dimethyloctylamine (DMOA) to the eluent will
      results in a dynamically coating of the stationary phase. Addition of DMOA to the
      eluent resulted for protonated basic compounds in a reduction of both enthalpy
      and entropy. In practice, with DMOA in the eluent symmetrical peaks were
      obtained. It is assumed that this is due to blocking residual silanols and/or ion
      exclusion effects.

PMID- 12198858
TI  - Fluidisation and dispersion behaviour of small high density pellicular expanded
      bed adsorbents.
AB  - The fluidisation and dispersion properties of various agarose-based expanded bed
      matrices--small high density stainless steel cored prototypes and standard
      commercial types--were studied in 1-cm diameter expanded bed contactors in which
      fluid entering the column base is locally stirred. In all cases, fluidisation
      behaviour was poorly predicted from the Richardson-Zaki correlation, with
      experimentally determined values of the expansion index being considerably higher
      than the theoretical values. The resons for these discrepancies are discussed in
      detail and the validity of applying this widely used correlation for
      characterisation of expanded bed systems is questioned. Residence time
      distribution studies using acetone tracers, demonstrated that in comparison to
      existing commercial supports, the small pellicular prototype materials generally
      possessed far superior hydrodynamic properties, which augurs well for their
      future employment in expanded bed chromatographic separations.

PMID- 12198859
TI  - Organic modifiers for the separation of organic acids and bases by liquid
      chromatography.
AB  - A straight-chain alcohol or diol additive in the mobile phase was used to modify
      and improve the HPLC separation of organic acids and bases. Incorporation of 2% 1
      butanol, 1% 1,2-hexanediol, or 0.25% 1,2-octanediol into an aqueous mobile phase
      greatly improved the separation of alkane carboxylic acids on a silica C18
      column, both in terms of separation time and peak shape. When 1.5% 1-hexanol,
      0.09% 1-decanol or 0.01% 1-dodecanol was added to an acetonitrile-water (30:70)
      mobile phase, much sharper peaks and better resolution were obtained for aromatic
      bases separated on an underivatized polystyrene-divinylbenzene column. The mobile
      phase additive is believed to coat the stationary phase surface by a dynamic
      equilibrium. The coated surface is more hydrophilic and facilitates the efficient
      partitioning of analytes between the mobile and stationary phases.

PMID- 12198860
TI  - Energetic heterogeneity of the surface of a molecularly imprinted polymer studied
      by high-performance liquid chromatography.
AB  - The influence of thermal annealing on the surface homogeneity of a polymer
      imprinted against L-phenylalanine anilide (LPA) was examined using high
      performance liquid chromatography (HPLC) for the measurement of the adsorption
      isotherms. The isotherms obtained for LPA and for its enantiomer, D-phenylalanine
      anilide (DPA) were fitted to the Freundlich (F) equation which accounts for the
      energetic heterogeneity of the surface with a separate parameter. Changes in the
      adsorptive properties of the polymer produced by thermal annealing were deduced
      by comparing the heterogeneity parameters given by the nonlinear regression.
      These changes were also illustrated by deriving the isosteric heats of adsorption
      as functions of the amounts adsorbed and by calculating the associated affinity
      distributions. This latter technique involves an application of the affinity
      spectrum (AS) combined with the F adsorption model. The plausibility and accuracy
      of the combination is discussed. It is shown that the derivation of the
      amplitudes of the affinity distributions from the F parameters is inaccurate,
      making difficult the proper estimate of the changes in the total population of
      adsorption sites. In contrast, the AS method gives correct estimates of the
      parameter that characterizes the slope of the affinity distributions. The results
      derived from the three sets of results (F model parameters, isosteric heats of
      adsorption, AS + F method) show consistently that annealing reduces the energetic
      heterogeneity of the polymer surface for both LPA and DPA. In practice, however,
      the improvement of the polymer performance in HPLC is relatively limited.

PMID- 12198861
TI  - Biomechanical influences of head posture on occlusion: an experimental study
      using finite element analysis.
AB  - The biomechanical influences of head posture on the cervical column and
      craniofacial complex during masticatory simulation were quantified using three
      dimensional (3D) finite element analysis (FEA). Three types of finite element
      model (FEM) were designed to examine relationships between the position of the
      head and malocclusion. Model A was constructed to have a standardized cervical
      column curve, model B a forward inclined posture, and model C a backward inclined
      posture. The results of the spinal displacements revealed that model B moved in a
      forward direction and model C in a backward direction during masticatory
      simulation. The stress distributions on the cervical column (C1-C7) for models A,
      B, and C showed differences; stress converged at the atlas in model A, high-level
      stresses were observed at the spinous processes of C6 and C7 in model C, and the
      stress converged at the anterior edge in the vertebral body of C4 of model B.
      Stress distribution on the occlusal plane and maxillofacial structure did not
      show absolute differences among the three models. Alteration of head posture was
      directly related to stress distribution on the cervical column, but may not
      always directly influence the occlusal state.

PMID- 12198862
TI  - Correlation between facial morphology, mouth opening ability, and condylar
      movement during opening-closing jaw movements in female adults with normal
      occlusion.
AB  - The aim of this study was to investigate the relationship between parameters of
      facial morphology, maximal voluntary mouth opening ability, and condylar
      movements in 21 adult females, aged between 20 and 24 years. The subjects had a
      normal occlusion without sign or symptoms of temporomandibular joint (TMJ)
      dysfunction. Mandibular movements were recorded using an opto-electric jaw
      movement recording system with six degrees of freedom under a series of maximal
      mouth opening-closing movements. Maximal jaw opening and coincident condylar
      movement were measured three-dimensionally. The mean values of the incisor and
      condylar path were 41.1 +/- 3.5 mm (range 35.6-50.9 mm) and 12.8 +/- 2.8 mm
      (range 8.1-19.2 mm), respectively. Although the positive correlation between
      maximal jaw opening and facial morphology was significant, none of the variables
      significantly differed between the value of the condylar path and facial
      morphology. The length of the path of maximum incisor movement and the condylar
      path during mandibular movement also did not correlate. Stepwise multiple
      regression analysis indicated a positive association between the maximal length
      of the incisor path and the cephalometric value of mandibular ramus inclination
      (R2 value was 0.369). The results of this study suggest that facial morphology
      size has a limited effect on maximal voluntary mandibular opening and condylar
      movements in normal adult female subjects.

PMID- 12198863
TI  - Chair-side procedure for connecting transpalatal arches with palatal implants.
AB  - The present investigation examined a chair-side procedure for connecting a
      transpalatal arch (TPA) with palatal implants, which does not involve any
      laboratory work. This new technique was compared with the standard procedure in
      terms of the number of steps, the time required, and the cost. The total chair
      side time needed with the standard procedure was 38 minutes, with the material
      costs amounting to [symbol: see text] 159.6. With the chair-side procedure the
      total time required was 55 minutes, and the cost of the material totalled
      [symbol: see text] 34.1. The chair-side procedure was derived from orthodontic
      treatment concepts and is independent of laboratory input. Its major advantage is
      that it does not require transfers, which necessitate additional steps. These
      steps, which are inevitable with the standard procedure, resulted in an
      unexpectedly high cost level and increased the total cost. The difference in the
      cost of the material between the two procedures amounted to [symbol: see text]
      125.5 and timewise the difference was 17 minutes. Whilst TPA-implant connections
      can be made with both the standard and chair-side procedures, the standard
      procedure, although taking considerably less chair-side time, was four times more
      expensive than the chair-side procedure.

PMID- 12198864
TI  - The efficacy of anterior repositioning splint therapy studied by magnetic
      resonance imaging.
AB  - Magnetic resonance images (MRIs) were obtained of 52 temporomandibular joints
      (TMJs) of 30 patients with TMJ disease, before insertion of an anterior
      repositioning splint. Ten TMJs showed a normal disc-condyle relationship.
      Pathological findings were partial or complete anterior disc displacement with
      disc reduction (n = 18), without (n = 7), or with partial reduction (n = 4) or
      non-reducing joints combined with osteoarthrosis (n = 13). Associated clinical
      findings were joint clicking, painful TMJ movements with or without condyle
      limitation, deviation, or crepitus. The clinical evaluation when compared with
      the MRIs correlated in 75 per cent of cases. Immediate post-insertion MRIs showed
      recapture of discs with a protrusive splint in 15 out of 18 reducing
      displacements. Recapture of the disc was seen in only two out of four joints with
      anterior disc displacement with partial disc reduction. There was no recapture in
      non-reducing joints. In severe cases of internal derangement with a wide range of
      disc displacement combined with changes of the osseous joint surfaces, the
      recapturing of the articular disc with an anterior repositioning appliance was
      unsuccessful (0 of 13). The follow-up for pain relief after one week showed a
      significant reduction of symptoms, despite the fact that recapture of the
      dislocated disc occurred in only 17 of the 42 pathological TMJs. The possibility
      for disc recapture depends on the disc-condyle position and configuration, the
      integrity of the posterior attachment, and the degree of degenerative changes of
      the intra-articular structures, such as osteophytosis, condylar erosion, or
      flattening of the articular disc. This diagnostic information influences the
      method of treatment of TMJ disorders. In non-reducing joints or in the later
      stages of internal derangement of the TMJ, it is not possible to achieve a normal
      disc-condyle relationship using protrusive splints.

PMID- 12198865
TI  - Cranial base considerations between apnoeics and non-apnoeic snorers, and
      associated effects of long-term mandibular advancement on condylar and natural
      head position.
AB  - One hundred consecutively medically referred patients (58 apnoeic and 42
      asymptomatic snorers) were reviewed cephalometrically at six-monthly intervals (6
      30 months) following treatment for obstructive sleep apnoea (OSA) and/or habitual
      snoring by mandibular advancement. Eighty-seven males and 13 females (mean age 49
      years, SD 8.5, range 33-74) were included in this study. Reference points and
      planes in the cranial base, nasopharynx, and mandibular condyle were digitized
      with a Reflex Metrograph and their means converted to linear and angular
      measurements. No statistically significant differences were observed between the
      apnoeic and non-apnoeic groups in either their skeletal or cranial base
      measurements. All linear cranial base dimensions were, however, reduced in the
      apnoeic group, with the exception of the distance (S-SE). Following mandibular
      advancement, statistically significant changes were observed in vertical condylar
      position (Cd-vert) with changes occurring at 6 (P < 0.012), 18 (P < 0.043), and
      24 months (P < 0.007). No changes in horizontal condylar position (Cd-horiz) were
      found. Significant changes were observed in natural head position (NHP) with a
      reduction from an extended (NSL-vert 99.7 degrees) to a more upright NHP (NSL
      vert 93.0, P < 0.001).

PMID- 12198866
TI  - Periodontal 5'-deiodination on forced-induced root resorption--the protective
      effect of thyroid hormone administration.
AB  - The present investigation was designed to study the protective effect given by
      thyroid hormone (TH) on root resorption: (1) whether intra-peritoneal versus oral
      TH administration had the same efficiency; and (2) whether this effect involved
      local or systemic mechanisms. For this purpose, circulating T3 levels, systemic
      alkaline phosphatase (APase) activity, and 5'deiodinase (5'D) activity were
      evaluated in the periodontal area of 80 Sprague-Dawley rats, 8 weeks of age, in
      which orthodontic appliances had been inserted. The results showed that TH
      treated animals (intra-peritoneal or oral) had significantly less force-induced
      root resorptive lesions compared with a control group, without apparent changes
      in T3 or APase levels, and that periodontal remodelling was accompanied by a
      significant increase in local T3 generation as a result of T4 deiodination. This
      5'D activity was higher in those animals that received exogenous TH. These
      results suggest that this protective TH mechanism may be achieved at a local
      level and that administration of low doses of TH may play a protective role on
      the root surface either during orthodontic treatment or in those patients that
      present spontaneous root resorptive lesions.

PMID- 12198867
TI  - Fluoride-releasing elastomeric ligatures assessed with the in situ caries model.
AB  - The in situ caries model was used to assess the clinical benefit of fluoride
      releasing elastomeric ligatures. The design of the experiment was a longitudinal,
      prospective, randomized, crossover clinical trial. Fourteen individuals starting
      orthodontic treatment with fixed appliances were recruited. Three in situ enamel
      specimens, with preformed subsurface carious lesions, were prepared for each
      patient, from human premolars. Two were placed in customized holders and one was
      retained as a control specimen. A crossover design was used so that patients had
      two experimental periods of six weeks with either fluoridated or non-fluoridated
      elastomerics, and a washout between. Elastomerics were randomly allocated at the
      first visit and one enamel specimen was placed at the beginning and collected at
      the end of each experimental period. The specimens were sectioned and ground to
      100 microns, and transverse microradiography was carried out. They were analysed
      using dedicated computer software. The outcome measure was the change in the
      parameters of the pre-formed carious lesion, expressed as mineral loss (delta Z),
      lesion depth (ld), lesion width (lw), and ratio (delta Z/ld) between the three
      specimens. The mean mineral loss (vol %.micron) for the control specimen was
      403.7 (+/- 139.5), compared with 599.3 (+/- 515.4) for the non-fluoridated
      ligatures and 477.2 (+/- 298.4) for the fluoridated ligatures. A one-factor
      within subjects ANOVA showed no statistical difference between the groups (P =
      0.376). Fluoride-releasing ligatures do not provide a significant anti-cariogenic
      benefit in patients undergoing orthodontic treatment. This may be due to the
      short-term nature of the fluoride release. However, they might affect the local
      environment surrounding the bracket.

PMID- 12198868
TI  - Floating norms and post-treatment overbite in open bite patients.
AB  - In this study, the clinical significance of three floating norm systems, the
      Bergen Box (BB), the Segner-Hasund Harmonybox 1 and 2 (SHH1 and SHH2), as well as
      the influence of treatment modalities for predicting results of an open bite
      treatment were investigated. In the BB and SHH1, patients with a steep mandibular
      plane angle or a skeletal open bite configuration (O1mand, O1mandmax, O1max, or
      N1mand) were considered 'high risk', while in the SHH2, only the configurations
      O1mand and O1mandmax were considered high risk. All other configurations were
      designated 'low risk'. It was postulated that in high risk patients, the overbite
      was likely to relapse into an open bite after retention. Cephalograms of 83 open
      bite patients taken before treatment (T1) and at the end of retention (T2) were
      studied. Patients designated as low risk generally had a normal overbite at T2
      after treatment, regardless of which box was used. The risk configurations of the
      SHH1 and SHH2 at T1 were significant predictors of the overbite at T2, the first
      being slightly better compared with the SHH2. The main clinical values of the
      SHH1 and SHH2 are strongly supported by the relatively good success rate in
      distinguishing a low-risk configuration. Reliable prediction of the treatment
      results of high-risk patients with risk configurations according to the SHH is
      improved by evaluating treatment modalities. The posterior bite splint seemed to
      have a bite opening effect, while a bite closing effect was associated with the
      use of a removable retention appliance.

PMID- 12198869
TI  - Changes in alveolar morphology during open bite treatment and prediction of
      treatment result.
AB  - It has been postulated that dentoalveolar height is enlarged by a compensation
      mechanism in long face subjects. In this study, dentoalveolar composition was
      studied in 83 open bite patients. It was found that increases in overbite during
      treatment coincided with vertical lengthening of the symphysis, which exceeded
      increments in lower face height. This vertical growth coincided mainly with an
      increase in the area of the symphysis. Furthermore, a retrusion of the maxillary
      incisors enhanced bite deepening. Stability of the overbite during the retention
      period was studied in a subset of 22 patients. It was found that retrusion of the
      maxillary incisors during treatment led to a more stable overbite during the
      retention period. Vertical lengthening of the symphysis relative to the increase
      in lower face height seemed to enhance bite opening during retention. Prediction
      of the overbite may be reliable, if a re-evaluation of the patients takes place
      during active treatment. The angle NTGoGn had a substantial predictive value
      (multiple R = 0.46) for post-treatment overbite. It is concluded that in open
      bite patients, a dentoalveolar compensation mechanism results in a stable
      overbite at the end of treatment by enlarging symphysial height through a
      moderate increase in symphysial volume. In addition, retrusion of the maxillary
      incisors contributes to overbite reduction. However, an excessive increase in
      vertical height of the symphysis relative to lower face height may relapse after
      active treatment. For prediction of the post-treatment overbite, the angle NTGoGn
      may be used, although a re-evaluation during treatment is recommended.

PMID- 12198870
TI  - Vertical changes following orthodontic extraction treatment in skeletal open bite
      subjects.
AB  - The purpose of this investigation was to assess the vertical changes occurring in
      skeletal open bite patients treated orthodontically with different extraction
      patterns. The study was conducted using lateral cephalometric radiographs taken
      before and after treatment. Fifteen patients who had an anterior open bite (AOB)
      only were treated with first premolar extractions (Group E4). Seventeen patients
      with an AOB extending to the posterior teeth were grouped according to the
      extractions: extraction of second premolars (Group E5) and first molars (Group
      E6). Cephalometric data were analysed according to the 'two-factor experiment
      with a repeated measure on one factor' model. The treatment group factor had
      three levels, E4, E5, and E6, and the time factor two levels, pre- and post
      treatment. The differences between the pre- and post-treatment periods were
      statistically significant for all the cephalometric variables (P < 0.001, P <
      0.0001), except for ANS-Me/Na-Me. The time and group interaction were found to be
      statistically significant for the variables where the time factor is important,
      such as SN-GoGn angle, SGn-NBa angle, ANS-Me dimension, Na-Me dimension, forward
      movement of the maxillary and mandibular molars, and the distance to the
      mandibular plane of the lower molars. The severity of vertical dysplasia did not
      change in group E4. Generally, however, within the appropriate indications,
      extraction of the second premolars or the first molars led to a closing rotation
      of the mandible in subjects with a skeletal AOB extending to the posterior teeth.

PMID- 12198871
TI  - [Bacterial meningitis: anticipating threatening complications. Brain in a vise
      grip].

PMID- 12198872
TI  - [Therapeutic angiogenesis awakens hope. New blood vessels for arterial occlusive
      disease patients? (interview by Dr. Judith Neumaier)].

PMID- 12198873
TI  - [The anti-obesity drug sibutramine for overweight diabetic patients. "Blood
      pressure is not elevated")].

PMID- 12198874
TI  - [Reflux, smoking, alcohol. Approach to prevention of esophageal carcinoma].
AB  - In western industrialized countries, esophageal cancer is a rare entity. While
      smoking and alcohol are the major risk factors for squamous cell carcinoma, the
      most important etiological factor for adenocarcinoma is Barrett's esophagus
      caused by gastro-esophageal reflux. Over the past few decades there has been a
      dramatic increase in the incidence of adenocarcinoma. The prognosis for both
      types of esophageal cancer is poor, with a 5-year survival rate of < 10%. Only
      early stages have a good prognosis. While prevention of squamous cell carcinoma
      is limited to avoiding drinking and smoking, prevention of adenocarcinoma
      requires endoscopic surveillance of Barrett's esophagus and the treatment of any
      dysplasia arising in it.

PMID- 12198875
TI  - [Peptic stenosis, motility disorder or carcinoma. What is ate the bottom of
      dysphagia?].
AB  - Dysphagia is the characteristic cardinal symptom of diseases of the esophagus.
      Etiologically, consideration must first be given to carcinoma of the esophagus.
      Among the cancers affecting this organ, adenocarcinoma of the distal part of the
      esophagus is the most common. The most important differential diagnosis in
      patients who have difficulty swallowing is peptic stricture of the distal
      esophagus arising from long-standing reflux disease. Further possible causes are
      motility disorders of the esophagus including, in particular, achalasia and--more
      rarely--diverticula, foreign bodies, membranes or rings, benign tumors or
      extraluminal processes.

PMID- 12198876
TI  - [Esophageal carcinoma in an advanced stage. The value of surgery plus
      radiochemotherapy].

PMID- 12198877
TI  - [National practice guideline for diabetes. Managing your diabetic patient
      properly].

PMID- 12198879
TI  - [Fit instead of fat. Exercise as therapy for overweight hypertensive patients].

PMID- 12198878
TI  - [No grounds for Barrett hysteria. Current monitoring strategies are adequately
      reliable].

PMID- 12198880
TI  - [My child stutters! Which speech disorders are to be treated by a specialist?].
AB  - The etiology of stuttering is multifactorial. Developmental disturbances in
      "speech flow" usually clear up within six months. However, inappropriate
      reactions on the part of the child's surroundings (parents, unqualified
      physicians), but also psychosocial problems, may consolidate the disorder.
      Chronic stuttering may, under certain circumstances have far-reaching
      consequences for communication and social behavior, and even impact negatively on
      the victim's subsequent occupational life. A qualified diagnostic work-up leading
      to appropriate early pedaudiological and logopedic therapeutic measures can
      prevent this negative development.

PMID- 12198881
TI  - [Flatulence, meteorism, fullness. Plant cocktail calms the irritated stomach].

PMID- 12198882
TI  - [Diabetes mellitus, smoking, alcohol drinking, hypercholesterolemia. Screening of
      these stroke risk factors?].

PMID- 12198883
TI  - [What is the significance of this nodule? "Pea" in the hand dorsum].

PMID- 12198884
TI  - [A disease management program since July 1. But only on a trial basis].

PMID- 12198885
TI  - [How sick your patients are. Every fifth patient is a diabetic, every second
      patient is hypertensive].

PMID- 12198886
TI  - [The result of neglected or erroneous treatment. Mentally handicapped by hay
      fever].

PMID- 12198887
TI  - [Fixed combination of AT1 blocker and diuretic. Stroke preventive combination for
      hypertension].

PMID- 12198888
TI  - [A new synthetic coagulation inhibitor. Only half as many thromboembolisms].

PMID- 12198890
TI  - [Inadequate blood glucose control with oral antidiabetic drugs. Early conversion
      to insulin].

PMID- 12198889
TI  - [Osteoporosis therapy. A comparison of bisphosphonates].

PMID- 12198891
TI  - [Cardiac protection by beta-1 selective beta blocker. Still better in the 3rd
      generation?].

PMID- 12198893
TI  - [Ambient air and human health in Samara Region].

PMID- 12198892
TI  - [Ambient air pollution and human health in the town of Nizhnekamsk].
AB  - The paper gives hygienic characteristics of ambient air pollution and examines
      human health in the town of Nizhnekamsk. There are worse demographic indices. In
      the structure of morbidity, respiratory diseases make up the largest proportion
      (44.4%), injuries and poisoning rank next (16.9%), skin and skin fate occupy the
      third place (5.4%). There are the highest morbidity rates in the polluted areas
      of the town. In these areas, respiratory allergoses (preasthma and bronchial
      asthma) occur more frequently than in the controls.

PMID- 12198894
TI  - [Comprehensive hygienic assessment of the environment and human health in the
      Primor'e Territory].
AB  - The study has used mathematical and statistical analysis of causal relationships
      of human health and forming environmental factors in the Primorye Territory. A
      scheme has been development for integral assessment of the anthropoecological
      system as the human environment and human health. The Primorye Territory has been
      divided by the degree of environmental tension. The priority environmental
      factors on morbidity in the Territory have been determined.

PMID- 12198895
TI  - [Impact of lead-induced environmental pollution on children's health in
      Mongolia].
AB  - Studies were undertaken to evaluate lead-induced environmental pollution in the
      urban and rural areas of Mongolia. There was a correlation between blood lead
      levels in children and the lead pollution of air, soil, snow cover, which is well
      known to affect children's morbidity.

PMID- 12198896
TI  - [Hygienic assessment of the results of the "Pure Air" programme].

PMID- 12198897
TI  - [Formation of organochlorine compounds in the chlorination of water containing
      industrial contaminants: Experimental assessment and forecasting].
AB  - The hazard of GSS production from commercial chemicals was evaluated during water
      chlorination by analyzing the results of experimental study of chlorination of
      chemicals from different classes. Structural fragments were found, their presence
      in the molecule determined the capacity of a substance to undergo intensive
      transformation to form GSS. The regularities that associates the structure of a
      substance with the rate of chlorination were detected. Some theoretical
      approaches to the determination of the ability of chemical to chlorinate are
      outlined.

PMID- 12198898
TI  - [Perspectives of improvement of water disinfection technology in superficial
      sources].

PMID- 12198899
TI  - [Topical problems of improvement of sanitary and epidemiological surveillance in
      environmental hygiene].

PMID- 12198900
TI  - [Smoking: Epidemiology and prevention].
AB  - The paper presents data available in the literature and the author's own data on
      the spread of smoking in different age and social groups.

PMID- 12198901
TI  - [Use of geoinformational systems for epidemiological studying malignant laryngeal
      neoplasms in Krasnoyarsk].
AB  - This paper shows it possible to use geoinformational systems for mapping and
      analyzing medical statistical data on those with malignant laryngeal neoplasms.
      The fact that the distribution of the patients can be shown on the map of a town
      in relation to the location of their houses (if they have an address) allows
      differentiation of the ecological living conditions of these patients, which in
      turn makes it possible to put not only high morbidity areas on the map of a town,
      but also to consider the characteristics of the environment in these areas.

PMID- 12198902
TI  - [On systemic training of preventive medical specialists under the present
      conditions].
AB  - The results of a systemic approach to training the students of the Faculty of
      Preventive Medicine, I. P. Pavlov Ryazan State Medical University during the
      reorganization of higher medical education in the country, which covered pre
      higher higher, and post-higher education are presented. Prehigher education on
      the basis of school and the university assumes that students will obtain extended
      theoretical and practical skills in chemistry, anatomy, and biology. Higher
      education at the stage of propedeutic hygiene forms in students ideas of the
      significance of environmental factors for human health, the threshold of their
      action, and sanitary standardization.

PMID- 12198903
TI  - [Changes in psychophysiological variables in students during examinations].
AB  - Current psychological tests and classic methods for recording and calculating
      autonomic correlates were used to study changes in students' psychophysiological
      indices during examinations. During this period, the students were found to
      develop emotional stress characterized by a complex of psychophysiological and
      autonomic changes. The nature and direction of the latter were determined by the
      individual and typological properties the examinees, by the significance of the
      emotional and stress situation of the autonomic nervous system and its
      responsiveness.

PMID- 12198904
TI  - [Hygienic value of glycosylates from the Brassica family plants].

PMID- 12198906
TI  - [Time course of changes in the development of preschool children in Krasnoyarsk].
AB  - To study the time course of changes in the growth and development in children,
      the indices of physical and biological development were studied in 1935 children
      aged 3 to 7 years who went to the preschoolchildren's establishments in
      Kransnoyarsk in 1989-1990 and 1999-2000. There were increases in the number of
      children with intrauterine hypotrophy and in that of preschoolchildren with
      retarded biological development. In the pattern of disharmonious variants of
      physical development there was a rise in the proportion of obese children and a
      reduction in that of lean children. These trends suggest that there are negative
      changes in the growth and development of children in Kransnoyarsk.

PMID- 12198905
TI  - [Role of social and biological factors in the formation of health in preschool
      children].
AB  - To study the influence of social and hygienic factors on the health and physical
      development of children aged 4-7 years in Kazan, they underwent a comprehensive
      medical examination and the sociological characteristics of their parents were
      analyzed. The health and harmony of physical development in children were found
      to be largely associated with by their parents' education, age, marital status,
      by the quality of child care, and with the time the children began visiting
      preschool educational establishments. Thus, the questionnaire data suggest that
      sociohygienic and biomedical factors unfavourably influence the health and
      physical development of preschool children.

PMID- 12198907
TI  - [Changes in short-term memory in young schoolchildren during studies].
AB  - Daily variations in short-term visual and hearing memory were found in 8-10-year
      old children. It was ascertained that they were not optimized with the learning
      time in most children. In 70% of the children, individual daily variations in
      short-term memory of all modalities were asynchronous. In these children, the
      mean daily volume of short-term hearing memory was much more than that of short
      term visual one. The girls could reproduce the greater volume of visual
      information than could be boys.

PMID- 12198908
TI  - [Health and physical activity in adolescents of today].
AB  - The results of clinical and epidemiological studies conducted by the researchers
      of Research Institute of Hygiene and Care of Children and Adolescents, Health
      Research Center, Russian Academy of Medical Sciences, are indicative of a
      substantial deterioration of health in adolescents in the late 20th century.
      Inactivity typical for young people of today has been found to be a major risk
      factor of cardiovascular functional disorders and metabolic osteopathies whose
      prevalence has increased among adolescents. There is evidence for that there is
      an association of low activity with the occurrence of calcium homeostatic
      disorders that result in osteomuscular diseases, cardiovascular functional
      disorders, deteriorated physical development, decreased functional (force)
      capacities of the growing organism in adolescents. In addition to inactivity,
      excessive exercise experienced by young athletes also causes marked disorders, in
      girls in particular.

PMID- 12198910
TI  - [Children's health in the petroleum region of the Republic of Tatarstan].
AB  - The paper provides a comprehensive assessment of the ecological situation of the
      most polluted town of the petroleum region. In-depth studies were made in 309
      children aged 4-6 years from 4 children's preschool establishments. It was found
      that only 37.5% of the preschool children were apparently healthy, allergic
      diseases were detected in 27.2% of the children, cardiovascular ones were found
      in 18.8% of the examinees. Eighteen of the 309 children were classified as
      frequently ill. The physical development of children in the polluted area was
      less than that in the controls.

PMID- 12198909
TI  - [Somatic and functional potential in schoolchildren in relation to different
      motor activity patterns].

PMID- 12198911
TI  - [The electric properties of fiber surface and the toxicity of asbestos].
AB  - Thermal treatment, autoclaving and their combination yielded 3 samples of
      chrysotile-asbestos. With these, as compared with parent Type PRZh-1-50 Bazhenov
      chrysotile, the structure of fibers deteriorated and the number of negative
      discharges increased in the first two samples; the superficial structure
      substantially increased and the number of positive centers greatly decreased in
      the third sample. The ratio of positive to negative centers was less in all
      treated samples than that in the parent one, it decreased particularly during
      combined treatment. In this sample, hemolytic and mutagenic activity and
      cytotoxicity were substantially decreased; carcinogenic activity was greatly
      decreased (by 4 times) (as shown by the pleural mesothelioma indication test
      during intrapleural administration to rats). Thermal treatment and autoclaving
      insignificantly lowered the hemolytic activity and mutagenicity; carcinogenicity
      of these samples was much less (by 2.3 and 2 times) than that of parent
      chrysotile.

PMID- 12198913
TI  - [Current methods for studying the impact of environmental pollution on the immune
      system].

PMID- 12198912
TI  - [Hygienic assessment of components of smoking fume].
AB  - Analyzing the chemical composition of smoking fume has indicated that maximum
      allowable concentrations (MACs) have been established for 50 of 400 well-known
      compounds, working area MACs were standardized for 42 of the 50 compounds, the
      maximum single and daily average concentrations were standardized for 34 and 30
      compounds, respectively. All standards were established for 25 compounds. Despite
      the fact that there a large list of MACs, it is difficult to calculate the
      objective hygienic risk of smoking smoke since 32 compounds are contained in
      traces. Hygienic assessment of fume discharges from the smoking chamber by taking
      into account their mass and MACs demonstrated that phenols, carbonyl compounds,
      acids, and benz(a)pyrene which should be used to work out the unified hygienic
      standard are of the greatest importance.

PMID- 12198914
TI  - [Methods for studying the composition of transformation products of
      organophosphorus compounds in the ambient air].

PMID- 12198915
TI  - [Gas chromatographic determination of 2-chlorophenol traces in biological
      fluids].

PMID- 12198916
TI  - [Potentialities of low-frequency conductometry in the assessment of mineral
      waters].

PMID- 12198917
TI  - [The specific features of radio-ecological monitoring data].

PMID- 12198918
TI  - [Sociohygienic monitoring in the solution of strategic tasks of the environment
      and human health].

PMID- 12198919
TI  - Chronic obstructive pulmonary disease surveillance--United States, 1971-2000.
AB  - PROBLEM/CONDITION: Chronic obstructive pulmonary disease (COPD) includes chronic
      bronchitis and emphysema but has been defined recently as the physiologic finding
      of nonreversible pulmonary function impairment. This surveillance summary reports
      trends in different measures of COPD during 1971-2000. REPORTING PERIOD COVERED:
      This report presents national data regarding objectively determined COPD (1971
      1994); COPD-associated activity and functional limitations (1980-1996); self
      reported COPD prevalence, COPD physician office and hospital outpatient
      department visits, COPD hospitalizations, and COPD deaths (1980-2000); and COPD
      emergency department visits (1992-2000). DESCRIPTION OF SYSTEMS: CDC's National
      Center for Health Statistics (NCHS) conducts the National Health Interview Survey
      annually, which includes questions concerning COPD and activity limitations. NCHS
      collects physician office-visit data in the National Ambulatory Medical Care
      Survey, emergency department and hospital outpatient department data in the
      National Hospital Ambulatory Medical Care Survey, hospitalization data in the
      National Hospital Discharge Survey, and death data in the Mortality Component of
      the National Vital Statistics System. Data regarding pulmonary function were
      obtained from the National Health and Nutrition Examination Surveys (NHANES) I
      (1971-1975) and III (1988-1994), and data regarding functional limitation were
      obtained from NHANES III, Phase 2 (1991-1994). RESULTS: During 2000, an estimated
      10 million U.S. adults reported physician-diagnosed COPD. However, data from
      NHANES III estimate that approximately 24 million U.S. adults have evidence of
      impaired lung function, indicating that COPD is underdiagnosed. During 2000, COPD
      was responsible for 8 million physician office and hospital outpatient visits,
      1.5 million emergency department visits, 726,000 hospitalizations, and 119,000
      deaths. During the period analyzed, the most substantial changes was the increase
      in the COPD death rate for women, from 20.1/100,000 in 1980 to 56.7/100,000 in
      2000, compared with the more modest increase in the death rate for men, from
      73.0/100,000 in 1980 to 82.6/100,000 in 2000. In 2000, for the first time, the
      number of women dying from COPD surpassed the number of men dying from COPD
      (59,936 versus 59,118). Another substantial change observed is that the
      proportion of the population aged < 55 years with mild or moderate COPD, on the
      basis of pulmonary function testing, decreased from 1971-1975 to 1988-1994,
      possibly indicating that the upward trends in COPD hospitalizations and mortality
      might not continue. INTERPRETATION: COPD is a major cause of morbidity,
      mortality, and disability in the United States. Despite its ease of diagnosis,
      COPD remains an underdiagnosed disease, chiefly in its milder and more treatable
      form.

PMID- 12198920
TI  - [Fungal esophagitis].
AB  - The gastrointestinal mucosa is one of the principal portal of entry in systemic
      fungal infections. Esophagitis is the most frequent among the fungal infections
      of the gastrointestinal tract. The etiologic factors of fungal infections are
      various Candida species, most frequently Candida albicans. Due to the large
      number of asymptomatic patients, great attention should be paid to the
      predisposing factors (AIDS, cancer, antibiotic or steroid therapy). The diagnosis
      is based on the endoscopic picture, microscopic examination and culture of the
      mucosal brushings, and histological examination of the esophageal mucosa. The
      treatment is based on azol derivates, mainly fluconazole. In fluconazole
      resistant cases amphotericin B is the drug of choice. The rare complications are
      perforation, bleeding and stricture.

PMID- 12198921
TI  - [Ultrasound diagnosis of focal intrauterine lesions].
AB  - OBJECTIVE: To compare the efficacy of the conventional grey-scale real time
      ultrasound, color Doppler ultrasound (color flow mapping) and hysteroscopy in the
      diagnosis of circumscript intrauterine lesions, such as endometrial polyps and
      submucosal myomas. METHODS: Preoperative transvaginal ultrasound data of 124
      patients with focal intrauterine lesions, as confirmed by operative hysteroscopy,
      were elaborated. Using grey-scale ultrasound the detailed endometrial morphology,
      with color Doppler the vascularization pattern of the endometrium was examined.
      The ultrasound diagnosis, the hysteroscopic diagnosis and the histological
      diagnosis were matched and the sensitivity of conventional grey-scale ultrasound,
      color Doppler ultrasound and hysteroscopy were calculated. Age, menstrual and
      fertility status, medication and symptoms (abnormal bleeding) of patients were
      also evaluated. RESULTS: Of the 124 removed lesions the histological examination
      confirmed 114 endometrial polyps and 10 leiomyomas. Conventional grey-scale
      ultrasound was performed at 79 patients (TVS group), while 45 patient were
      examined by color Doppler ultrasound (TVCD group). In the TVS group the
      intrauterine lesion was detected in 59 cases, and the origin was also correctly
      diagnosed in 48 cases. In the TVCD group 42 lesions were detected, and the
      ultrasound diagnosis was consistent with the histological diagnosis in 41 cases.
      At hysteroscopy 118 endometrial polyps and 6 myoma were described. In this
      material the sensitivity of conventional transvaginal grey-scale ultrasound, the
      color Doppler ultrasound, and hysteroscopy in the detection of circumscript
      intrauterine lesions was 0.74, 0.93 and 1, respectively; in the diagnosis of the
      intrauterine lesion was 0.66, 0.91 and 0.97, respectively. Statistically
      significant differences were found between the ultrasound detection rates (p <
      0.05) and between the diagnosis rates (p < 0.01) of the TVS and the TVCD group.
      Abnormal menopausal bleeding, recurrent bleeding, infertility, and tamoxifen
      therapy were present with high frequency in clinical data. CONCLUSION:
      Visualization of the feeding vessels using color or power Doppler ultrasound
      imaging improves the detection rate and the ultrasound diagnosis of the
      circumscript intrauterine lesions, approaching the sensitivity of hysteroscopy.
      First line application is recommended for patients at risk, such as infertility,
      recurrent postmenopausal bleeding, or for patients receiving long term tamoxifen.

PMID- 12198922
TI  - [Aortic root replacement with pulmonary allograft (Ross procedure) in children.
      Early results].
AB  - INTRODUCTION: For infants and children with congenital aortic valve disease root
      replacement with pulmonary allograft (Ross procedure) is the preferred method of
      choice. PATIENTS/RESULTS: The authors have successfully applied this operation in
      12 children (age range from 2.5 to 17 years--mean 9 years, body weight from 12 to
      58 kg--mean 46 kg), one of whom has also required a Konno extension for long
      segment left ventricular outflow tract obstruction. The operation was complicated
      by early postoperative endocarditis in one case, and the child required redo
      homograft root replacement on the ninth postoperative day. All patients,
      including this one survived, and are doing well at present. CONCLUSIONS: In the
      Hungarian literature this is the first report on the Ross and Konno procedure in
      children. On the basis of our excellent early results, Ross procedure is the
      method of choice in aortic valve disease in children.

PMID- 12198923
TI  - [The role of focal infections in the pathogenesis of diseases].
AB  - Focal infections have a definite role in various infectious complications. They
      may cause local propagation, systemic infection (sepsis) and metastatic
      infections. In such complications eradication of focal infections may have a
      curative and/or preventive effect. Such a role of focal infections in diseases of
      immunopathological origin cannot be proven. In these disorders the persistence of
      focal infection is not necessarily required for the progression of the disease,
      and eradication of focal infection(s) has no curative effect. There are no
      sufficient evidence favouring a connection between dental, tonsillar, and
      urogenital focal infections and allergic or autoimmune diseases. We also lack
      evidence that eradication of focal infections, apart from rare instances, might
      influence the prognosis of such patients.

PMID- 12198924
TI  - [Endoscopic removal of a toothbrush from a 13-year-old girl's stomach].
AB  - A case of a 13-year-old girl is reported. She swallowed her toothbrush
      accidentally, the surgeon suggested the endoscopic examination. The teen-age,
      well-developed girl did not have complaints, there were five hours between the
      accident, and the starting of the examination. After the pharynx anaesthetization
      by Lidocaine spray, the endoscopy was performed by a video endoscope of GIF-130
      type. The brush was found in the stomach, but its handle went through the
      pylorus. Injury was not found on the esophagus and stomach mucosa. The patient
      and her mother were fully informed, and for their request, the removal of the
      toothbrush was attempted by using grasping forceps and polypectomy snare. It
      lasted nearly forty minutes and was ensured by the intensive care. The procedure
      was successful, the patient who tolerated it well, left the hospital after
      observation, without complaints.

PMID- 12198925
TI  - ["Peer review" in the Lakartidningen. Competent and unbiased, but should openness
      be also included?].

PMID- 12198926
TI  - [Drug withdrawal--clinically important but practically difficult].

PMID- 12198927
TI  - [Political work to reduce the use of tobacco is not easy. "If tobacco was a
      medication it would no longer be available on the market"].

PMID- 12198928
TI  - [Peer review: a closed system in need of reform].
AB  - Peer review is the process by which experts assess the quality of manuscripts
      submitted for publication in scientific journals. During the last decade, this
      system for quality control has been debated a lot and investigated
      scientifically. By now, there is a widespread consciousness among scientists
      regarding the deficiencies of this system for quality control. It is slow,
      expensive, subjective, prone to bias and easily abused. To comply with its
      important function, the peer review system has to be reformed. The most important
      reforms would be to make it an open process--that is, the removal of the
      anonymity of the reviewing experts, and to oblige all parties in the publication
      process, authors, editors, reviewers, to declare potential conflicts of interest.

PMID- 12198929
TI  - [Debate on peer review. Report from an international congress on peer review].

PMID- 12198930
TI  - [Swedish physicians smoke least in all the world. A new study of smoking habits
      and attitudes to tobacco].
AB  - Since 1969, studies of Swedish doctors' tobacco habits and attitudes have been
      carried out regularly every fifth year. The present investigation was made in
      2001 in the form of a questionnaire distributed to a random sample of 5% of
      Swedish doctors (n = 1,367). The response rate was 80%. The proportion of daily
      smokers was 6%, a figure that had not changed since 1996. More doctors had never
      smoked (44% compared with 38% in 1996). Most smokers were found among
      psychiatrists and surgeons (10%). The use of oral snuff had increased to 16%
      among male and 5% among female doctors (compared with 9% and 3% in 1996). About
      50% of the doctors believed that the use of snuff increased the risk of
      hypertension, angina pectoris, myocardial infarction and oral cancer. Protection
      of health was the main reason for not smoking (98%). An overall majority (92%) of
      doctors advise patients with lung diseases and pregnant women not to smoke, and
      only a few (16%) never give advice about smoking cessation to smokers with non
      smoking related diseases. Many doctors do not allow smoking in their homes (69%)
      and ask for smoke free hotel rooms (82%). The doctor as a role model for patients
      was regarded as important by 71%. The number of smokers in the general Swedish
      population was as low as 19% in 2001, achieving the WHO goal for the year 2000.
      The low, unchanged level of 6% of doctors who smoke daily indicates that it might
      be possible to achieve a target level of 5-10% among the general population. The
      slowly increasing use of snuff requires further studies.

PMID- 12198931
TI  - [Oocyte donation to be legalized in Sweden. Excellent results reported from other
      countries].
AB  - Oocyte donation is an effective solution for treating infertile women whose
      ovaries are non-functional. This infertility condition is known as premature
      ovarian failure and is most commonly caused by genetic or autoimmune diseases,
      chemo- or radiotherapy, severe endometriosis and ovarian cancer. Oocyte donation
      also benefits those women who have functional ovaries yet respond poorly to
      ovarian hyperstimulation for in vitro fertilisation. Not only does oocyte
      donation provide healthy oocytes to infertile women, it also allows any genetic
      diseases of the recipient to be avoided. The process is simple beginning with
      ovarian hormonal stimulation of the donor followed by trans-vaginal oocyte
      retrieval. The mature oocytes are then fertilised with the sperm of the
      recipient's partner and the resulting embryo is transferred to the uterus two to
      five days later. Careful counselling of all parties involved is necessary before
      commencing treatment. International experience using oocyte donation has been
      excellent revealing normal, healthy relationships between the children and their
      families. Until now, oocyte donation has been illegal in Sweden, yet on 25th
      April 2002 the Swedish Parliament accepted a change in the law regarding assisted
      reproduction. According to this new law, oocyte donation will be permitted in
      Sweden from the beginning of January 2003 providing new hope for infertile
      couples.

PMID- 12198932
TI  - [Evidence-based health care requires knowledge of cost-effectiveness].

PMID- 12198933
TI  - [Difficult standpoints to be taken by the committee of costs and subsidies].

PMID- 12198935
TI  - [Epidemiology versus clinical trial. A five-round-match on scientific
      reliability].

PMID- 12198934
TI  - [Health economic evaluation of recommended drug treatment].

PMID- 12198936
TI  - [Did medicine professor Roberg draw the first portrait of Linne?].

PMID- 12198937
TI  - [To be sick-listed or to take responsibility for own work capacity?].

PMID- 12198939
TI  - [What is the idea of IPULS, Institute of Professional Development of Physicians
      in Sweden and its activities?].

PMID- 12198938
TI  - [Legal rights connected to current involuntary treatment must be surveyed].

PMID- 12198940
TI  - [Standpoint or a miswording?].

PMID- 12198941
TI  - [The "Kalla fakta-debate". The TV decided to broadcast only "correct" answers].

PMID- 12198942
TI  - [Health benefits of change-overt to snuff].

PMID- 12198943
TI  - [Outlook on mankind and ignorance concerning mobility services].

PMID- 12198944
TI  - [Physicians and politics in 1940s--threats of strikes resulted in living wages].

PMID- 12198945
TI  - Symptomatic vertebral hemangioma: the treatment of 23 cases and a review of the
      literature.
AB  - It is the purpose of this study to analyze a group of 23 patients affected with
      hemangioma in one or more metameres of the vertebral column. On the basis of
      clinical examination and instrumental testing in time (minimum follow-up 12
      months, maximum 217 months) the following treatment options are discussed:
      medical treatment and clinical monitoring closer in time; palliative surgical
      treatment whether or not associated with embolization of vascular afferences of
      the lesion and adjuvant treatment; intralesional surgical treatment whether or
      not associated with embolization of the vascular afferences of the lesion and
      adjuvant treatment. Skeletal hemangioma is a hamartomatous proliferation of
      vascular tissue, more precisely of endothelial tissue. This is demonstrated by
      its anatomical identity with other tissues and the existence of exceptional
      skeletal and multiple tissue hemangiomatosis that begin during childhood.
      Hemangioma is the benign tumor that is most frequently localized in the spine,
      involving about 10% of the world population, as reported in the literature on
      autoptic studies. It is often a solitary lesion, usually localized in the
      vertebral body, although it may extend to the posterior arch. There is
      predilection for the thoracic region of the spine, while it less frequently
      occurs in the cervical and lumbar spines. Generally, it remains asymptomatic
      throughout the entire life of the subject, so much so that it is often difficult
      to establish the onset of the lesion. Symptomatic hemangiomas (less than 1% of
      all hemangiomas) are those that are accidentally discovered via radiograms; they
      are most often observed during adult age. The most common treatment used for
      vertebral hemangioma associated with pain is radiotherapy, even if clinical
      observation represents a reasonable choice. Surgical treatment, preceded when
      possible by embolization of the vascular afferences of the lesion, is often
      associated with radiation therapy in cases where there is neurologic compression
      in addition to pain. It was the purpose of this study to analyze the long-term
      results obtained in a group of 23 patients affected with symptomatic vertebral
      hemangioma.

PMID- 12198946
TI  - Chondrosarcoma of the ribs and sternum. Considerations on 20 cases treated.
AB  - Over the last 20 years at the Rizzoli Orthopaedic Institute in Bologna 20 cases
      of chondrosarcoma (CS) of the thoracic wall (14 males, 6 females, mean age 49
      years) have been submitted to surgery. Localization was costal in 11 cases,
      costosternal in 3, sternal in 3, costovertebral in 3. The most frequent
      histological variety was central with 15 observations. All of the cases were
      treated surgically. Exeresis was wide in 14 cases, marginal in 6. Reconstruction
      of the thoracic wall took place either by direct suturing or (14 cases) using
      prosthetic materials (Marlex mesh, 1 or 2 shapeable metal plates). Of the 20
      cases treated, 16 patients are still alive (80%) with a mean survival rate of
      33.5 months and a mean reduction in the postoperative ventilative index of
      function of less than 10%. The results obtained lead us to believe that surgical
      treatment involving wide exeresis is adequate, and the reconstruction method
      using Marlex mesh and metal plates is reliable.

PMID- 12198947
TI  - Shoulder prosthesis in reconstruction of the scapulohumeral girdle after wide
      resection to treat malignant neoformation of the proximal humerus.
AB  - Progress in preoperative chemotherapy and radiation therapy, both intra- and
      postoperative, has in time allowed for an increase in indications for shoulder
      implant surgery in malignant tumors, thus drastically reducing the number of
      amputations. The use of prostheses, particularly those of the more recent
      generation, respond to the needs to overcome the limits of loss of movement, as
      long as good anatomical reconstruction of the soft tissues, the premise for good
      functional and cosmetic recovery, is also possible. The current tendency is that
      of using modular shoulder prostheses that provide a wide variety of sizes. This
      type of prosthesis has surpassed custom made prostheses in terms of simplicity,
      adaptability and economy. The use of cementation in stabilization of the
      intramedullary stem has made them more stable even in the long term, allowing for
      early rehabilitation. The main problem in reconstruction with a prosthesis is the
      quantity of residual muscular tissue (deltoideus, extrarotators) and the
      stabilization system of the same to the prosthesis in order to avoid dislocation,
      which constitutes the main complication. It is the purpose of this study to
      present the clinical and functional results obtained in 23 implants carried out
      for primary malignant neoformation of the upper limb. The implants studied were
      of three types (custom made, modular in Cr-Co-Mb and Ti-Al-Va). The results
      reported show how a shoulder prosthesis can obtain good functional results,
      particularly when a part of the activator muscles of the shoulder such as the
      deltoideus and the extrarotators is preserved. When the contrary is true, the
      results obtained are modest because the prosthesis acts as a simple spacer.

PMID- 12198948
TI  - Lumbar disc herniation and cauda equina syndrome. Considerations on a pathology
      with different clinical manifestations.
AB  - The authors describe six cases of cauda equina syndrome (CES) with different
      clinical manifestations, etiopathogenetic causes, and degrees of disc prolapse.
      In three of the cases, the clinical onset was dramatic and acute, in the others
      it was a hemisyndrome (with acute onset in only 1 case). The site of the disc
      prolapse was L4-L5 in 3 patients, L3-L4 in 2 patients, and L5-S1 in 1 patient.
      The authors emphasize the need for the early recognition of the syndrome with a
      careful clinical examination and history of the patient, as well as timely
      treatment within 24 hours. For the sake of prevention, and particularly when the
      hernia is large, the authors suggest monitoring of the stability of the residual
      disc during surgery and postoperatively the use of a brace for at least one
      month.

PMID- 12198949
TI  - Hip arthroplasty in coxarthrosis secondary to Paget's disease.
AB  - A total of 5 hip arthroplasties implanted between 1997 and 2000 in 5 patients
      affected with coxarthrosis secondary to Paget's disease were reviewed. The
      quality of the pagetic bone (sclerotic and very vascularized) resulted in a
      slightly longer amount of time required for surgery because of the difficulty
      preparing prosthetic placement and intra- and postoperative blood loss exceeding
      the norm. Complications were not observed. Clinical results were good in 100% of
      cases. Radiographically, 2 stems were assembled in varus.

PMID- 12198950
TI  - Marchetti-Vicenzi nailing of humeral shaft fractures.
AB  - Between 1995 and 1999, 46 acute nonpathological humeral shaft fractures were
      treated with retrograde Marchetti-Vicenzi humeral nailing. The mean healing time
      of all fractures was 10.8 weeks. Forty-five fractures (97.9%) united primarily,
      and one needed bone grafting (2.1%). Function of the shoulder was excellent in 35
      patients (76.1%) and moderate in 11 (23.9%). Elbow function was also excellent in
      35 patients and moderate in 11. Global functional results were excellent in 16
      patients (34.8%), good in 22 (47.8%) and fair in 8 (17.4%). There were 4 cases of
      10 degrees varus malunion (8.6%), one case of 15 degrees varus malunion (2.1%),
      and one case of 15 degrees anterior angulation malunion (2.1%). These malunions
      were clinically well tolerated. Four patients required removal of the nail
      because of posterior elbow pain. Retrograde Marchetti-Vicenzi nailing is an
      acceptable alternative for the treatment of acute humeral shaft fractures with a
      low complication rate.

PMID- 12198951
TI  - Posterolateral instability of the elbow.
AB  - The authors describe a rare case of recurrent posterior post-traumatic
      subdislocation of the elbow in a male aged 40 years. From a clinical point of
      view, it is a highly disabling condition, due to lesion of the ulnar portion of
      the radial collateral ligament. It is produced at minimum degrees of flexion
      movement in the elbow and depending on the entity of capsuloligamentous injury it
      may occur with episodes of instability, recurrent subdislocation or recurrent
      dislocation. Treatment is surgery and capsuloligamentous reconstruction according
      to the Osborne-Cotteril method, which has allowed for very satisfactory results
      to be obtained.

PMID- 12198952
TI  - Primary osteogenic sarcoma of the clavicle. Case report.
AB  - The clavicle is an unusual site for any primary bone tumor, including osteogenic
      sarcoma. The authors report the case of a young girl aged 13 years who was
      affected with primary osteogenic sarcoma of the right clavicle, and who was
      treated by preoperative and postoperative chemotherapy and radical clavicle
      excision, including the acromioclavicular and the sternoclavicular joints.

PMID- 12198953
TI  - Suitability of orthopaedic day surgery in Emilia-Romagna.
AB  - The Emilia-Romagna Regional Authority has encouraged the development of day
      surgery practice in this healthcare program. This study analyzes the results of
      the program, with particular attention to the field of orthopaedics, with the aim
      of defining the type of operations that can be carried out in day surgery. There
      has been a marked increase in the rate of day surgery operations in all fields of
      surgery on the whole. However, in orthopaedics, the average rate was lower than
      the general trend. On the other hand, there has been an increased use of day
      surgery for some types of operations not included in those indicated by the
      region. Results of the data analyzed suggest that the use of day surgery for
      orthopaedics can be extended, and so can the regional indications for operations
      that can be performed by this method of treatment.

PMID- 12198954
TI  - Acid-induced cloud point extraction and preconcentration of polycyclic aromatic
      hydrocarbons from environmental solid samples.
AB  - The effectiveness of the acid-induced phase separation of anionic surfactants
      (acid-induced cloud point extraction, ACPE) to extract polycyclic aromatic
      hydrocarbons (PAHs) from different environmental samples (soils, sediments and
      sludges), prior to chromatographic analysis, was evaluated. Variables affecting
      the ACPE efficiency were optimised using a natural matrix (a harbour sediment,
      CRM 535). Temperature, surfactant concentration and stirring were of primary
      importance to maximise recovery, whereas temperature and surfactant/hydrochloric
      acid concentration influenced the volume of the surfactant-rich phase and
      therefore the preconcentration factor achieved. The optimal conditions (2% sodium
      dodecanesulphonate (SDoS), 4.2 M HCl, 60 degrees C, 1 h) were applied to the
      extraction of PAHs from various matrices and the ACPE recoveries compared to
      certified results from Soxhlet extractions. Recoveries obtained for four to five
      aromatic ring PAHs ranged from 71 to 98%. Uncertainties obtained using ACPE were
      similar to or lower than those provided for the certified values. The volume of
      the extracts ranged from 1 to 2 ml. The method did not require additional clean
      up or preconcentration steps.

PMID- 12198955
TI  - Automated capillary liquid chromatography for simultaneous determination of
      neuroactive amines and amino acids.
AB  - A method for the separation and quantitative determination of neuroactive amino
      acids (aspartate, glutamate, citrulline, arginine, glycine, taurine, gamma
      aminobutyric acid) and neuroactive amines (noradrenaline, dopamine and serotonin)
      in a single chromatographic analysis is presented. The method is based on pre
      column derivatization with o-phthalaldehyde and tert.-butyl thiol, on-column
      preconcentration and separation using 50 microns I.D. packed capillary columns,
      and detection by amperometry. Mass limits of detection are 80-900 amol for all
      neurotransmitters with RSDs of 0.71 and 4.6% or better for retention time and
      peak area, respectively. The method was demonstrated by application to the
      determination of neurotransmitters in microdialysis samples collected from
      striatum of live rats and tissue samples extracted from butterfly brains.

PMID- 12198956
TI  - Capillary electrophoresis with amperometric detection of curcumin in Chinese
      herbal medicine pretreated by solid-phase extraction.
AB  - In the present study, curcumin from Chinese herbal medicine turmeric was
      determined by capillary electrophoresis with amperometric detection (CE-AD)
      pretreated by a self-designed, simple, inexpensive solid-phase extraction (SPE)
      cartridge based on the material of tributyl phosphate resin. An average
      concentration factor of 9 with the recovery of > 80% was achieved when applied to
      the analysis of curcumin in extracts of tumeric. Under the optimized CE-AD
      conditions: a running buffer composed of 15 mM phosphate buffer at a pH 9.7,
      separation voltage at 16 kV, injection for 6 s at 9 kV and detection at 1.20 V,
      CE-AD with SPE exhibited low detection limit as 3 x 10(-8) mol/l (S/N = 3), high
      efficiency of 1.0 x 10(5) N, linear range of 7 x 10(-4) -3 x 10(-6) mol/l (r =
      0.9986) for curcumin extracted from light petroleum. The method developed
      resulted in enhancement of the detection sensitivity and reduction of
      interference from sample matrix in complicated samples and exhibited the
      potential application for routine analysis, especially in food, because a
      relatively complete process of sample treatment and analysis was described.

PMID- 12198957
TI  - Effects of temperature and flow regulated carbon dioxide cooling in
      longitudinally modulated cryogenic systems for comprehensive two-dimensional gas
      chromatography.
AB  - Two different modes of temperature regulation in longitudinally modulated
      cryogenic systems (LMCSs) for comprehensive two-dimensional gas chromatography
      (GC x GC) were compared. Carbon dioxide was used as coolant. In the first mode of
      operation, the temperature of the trap was regulated to pre-set temperature using
      a digital temperature controller ("the constant temperature mode"). In the
      second, the temperature was regulated to a fixed negative offset to the oven
      temperature by using a constant flow of CO2 ("the constant flow mode"). A number
      of problems were occasionally observed using the constant temperature mode: (1)
      severe band broadening of high boiling analytes in the second dimension; (2) non
      Gaussian reconstructed first-dimension peak profiles; (3) high background due to
      modulation of first-dimension column bleed. It was concluded that these problems
      were associated with inefficient solute remobilization at low LMCS trap
      temperatures (1 and 2) or large trap temperature fluctuations (3). These problems
      could be avoided or significantly reduced by using the constant flow mode. Best
      results were obtained as the trap temperature was kept about 70 degrees C below
      the oven temperature.

PMID- 12198958
TI  - Influence of chromatographic conditions on separation in comprehensive gas
      chromatography.
AB  - Comprehensive gas chromatography (GC x GC) is now established as a powerful
      technique, which offers unprecedented separation power. For complex samples, the
      distribution of peaks in the two-dimensional (2D) space still may need to be
      optimised. Since temperature (T) is a critical variable, and compounds can be
      shifted in relative positions on column 1 arising from temperature program rate
      (rT) changes, and since retention in the second dimension, D2 (2tR) is likewise
      affected by the prevailing T (elution temperature; Te), then any factors which
      alter Te will affect the extent of separation in D2. Since temperature program
      and carrier gas velocity rate will affect the Te of the solutes, these two
      factors are considered in this paper. Apart from these two parameters, results of
      different stationary phase choice for the second dimension column as well as the
      second dimension column length are reported. rT is found to have the most
      profound impact on the Te of solutes and will be more likely to cause an
      inversion of elution order if such behaviour can occur. Peak widths and 2tR
      increase with a decrease in Te. On the other hand, flow-rate has less impact on
      peak widths and 2tR although Te is affected by a change in flow-rate. Specific
      solute-stationary phase interactions will cause the elution order of certain
      solutes to be altered, and may be observed when a different stationary phase is
      employed as the second column, depending on the solute-stationary phase
      separation mechanism. Experiments conducted on different second dimension column
      length showed that although a longer column will lead to better separations, wrap
      around may confound the separation process and may cause the solutes from
      sequential modulation events to co-elute. Thus a suitable second dimension column
      phase and length must be employed in order to obtain good separation. The factors
      investigated in this study will cause different extents of changes in the solute
      elution order and solute separations, and will affect the 2D contour
      presentation.

PMID- 12198959
TI  - Characterization of polyarylamide fibers by inverse gas chromatography.
AB  - Two types of commercial polyaramide fibers have been characterized by inverse gas
      chromatography. Using the fibers as stationary phases, adsorption isotherms for
      nonane, decane and undecane were obtained. Specific surface areas and isosteric
      heats of adsorption were also obtained by this method. Experimental results have
      been discussed as a function of hydrocarbon--fiber interaction and fiber
      crystallinity.

PMID- 12198960
TI  - Chemometric detection of thermally degraded samples in the analysis of drugs of
      abuse with gas chromatography-Fourier-transform infrared spectroscopy.
AB  - We present a chemometric procedure for the identification of the reference
      standard chromatographic peak in cases where the GC-FTIR analysis of commercial
      standards results in the appearance of more than one peak in the GC chromatogram.
      The procedure has been designed for phenethylamines, which represent the class
      with the largest number of individual molecules on the illicit drug market, and
      which are abused for their stimulant and/or hallucinogenic effects. The
      similarity between their vapor-phase FTIR spectra was modeled using principal
      component analysis (PCA), and class identity was assigned on the basis of soft
      independent modeling of class analogy (SIMCA). Additional peaks could be assigned
      to impurities in the standards, but most often they were artifacts formed during
      the GC-FTIR analysis of thermolabile or chemically unstable compounds. The latter
      case is illustrated by the identification of the reference standard
      chromatographic peak and FTIR spectrum of the potent psychotropic amphetamine
      derivative N-methyl-1-(3,4-methylenedioxyphenyl)-2-butanamine (MBDB), and by the
      elucidation of the chemical changes that occur in the molecule of MBDB due to
      thermal degradation.

PMID- 12198961
TI  - Sensitive indoor air monitoring of monoterpenes using different adsorbents and
      thermal desorption gas chromatography with mass-selective detection.
AB  - A simple method using active trapping on adsorbents and thermal desorption
      followed by GC-MS analysis was developed for the indoor air monitoring of
      monoterpenes. The study was carried out using a dynamically generated atmosphere
      consisting of 11 monoterpenes: camphene, camphor, delta 3-carene, 1,8-cineol,
      limonene, linalool, alpha-pinene, beta-pinene, alpha-terpinene, gamma-terpinene,
      fenchyl alcohol. The influence of the different adsorbents Tenax TA, Tenax GR,
      Carbosieve SIII, Chromosorb 106 on the yield of six selected monoterpenes at
      indoor air concentrations was studied. The adsorbent Tenax GR gave relatively the
      best yields followed by Tenax TA. Detection limits of approximately 1 microgram
      m3 were determined with Tenax GR for most of the monoterpenes.

PMID- 12198962
TI  - Development of an analytical methodology for sarin (GB) and soman (GD) in various
      military-related wastes.
AB  - The Army requires analytical methods that can detect chemical agents down to the
      low part-per-billion (ppb) levels in their waste streams in order to meet various
      state regulations regarding the classification of hazardous waste. Analytical
      methods were developed for the measurement of sarin (GB) and soman (GD) at ppb
      levels that involved preconcentration of relatively large volumes (40-150
      microliters) of a chloroform extract onto a sorbent cartridge, followed by
      thermal desorption and analysis by GC-flame photometric detection. Certified
      reporting limits (CRLs) achieved with these methods ranged from 8.3 to 19 ppb for
      GB and from 1.8 to 5.3 ppb for GD in the three matrices screened. Method
      detection limits (MDLs) achieved with these methods ranged from 1.7 to 8.2 ppb
      for GB and from 0.39 to 1.2 ppb for GD. The methods are capable of achieving
      lower CRLs and MDLs with only minor modification.

PMID- 12198963
TI  - Analysis of organotin compounds by grignard derivatization and gas chromatography
      ion trap tandem mass spectrometry.
AB  - The determination of organotin compounds in water using gas chromatography-tandem
      mass spectrometry (GC-MS-MS) is described. Several organotin derivatives were
      synthesized by the reaction of organotin chlorides with Grignard reagents such as
      methyl-, propyl- and pentylmagnesium halides. After the optimization of the GC-MS
      MS conditions, several derivatizations with the Grignard reagents were compared
      by evaluating the molar responses and volatilities of the derivatives and
      derivatization yields. As a result, the derivatizing reagent of choice is
      pentylmagnesium bromide. Calibration curves for the mono-, di- and tributyltins
      and mono-, di- and triphenyltins with pentylmagnesium bromide were linear in the
      range of 0.5-100 pg of Sn. The instrumental detection limits of six organotins
      ranged from 0.20 to 0.35 pg of Sn. The recovery tests from water samples (500 ml)
      were performed by using sodium diethyldithiocarbamate (DDTC) as a complexing
      reagent. Except for monophenyltin, the absolute recoveries of organotins from
      pure water at 200 ng of Sn/l were satisfactory. The recoveries calibrated by
      surrogate compounds (perdeuterated organotin chlorides) ranged from 71 to 109%.
      The method detection limits ranged from 0.26 to 0.84 pg of Sn (500-ml sample).
      This method was applied to the recovery of organotins from river water and
      seawater. The calibrated recoveries were between 90 and 122%.

PMID- 12198964
TI  - Rapid estimation of octanol-water partition coefficients using synthesized
      vesicles in electrokinetic chromatography.
AB  - Vesicle electrokinetic chromatography (VEKC) using vesicles synthesized from the
      oppositely charged surfactants cetyltrimethylammonium bromide (CTAB) and sodium
      octyl sulfate (SOS) and from the double-chained anionic surfactant bis(2
      ethylhexyl)sodium sulfosuccinate (AOT) was applied to the indirect measurement of
      octanol-water partition coefficients (log Po/w). A variety of small organic
      molecules with varying functional groups, pesticides, and organic acids were
      evaluated by correlating log Po/w and the logarithm of the retention factor (log
      k') and comparing the calibrations. A linear solvation energy relationship (LSER)
      analysis was conducted to describe the retention behavior of the vesicle systems
      and compared to that of octanol-water partitioning. The solute hydrogen bond
      donating behavior is slightly different with the vesicle interactions using CTAB
      SOS vesicles as compared to the octanol-water partitioning model. The AOT vesicle
      and octanol-water partitioning systems showed similar partitioning
      characteristics. VEKC provides rapid separations for determinations of log Po/w
      in the range of 0.5 to 5 using CTAB-SOS vesicles and 0 to 5.5 using AOT vesicles.

PMID- 12198965
TI  - Theoretical study of incomplete sampling of the first dimension in comprehensive
      two-dimensional chromatography.
AB  - The process of regularly transferring material from the primary column to the
      secondary column is critical in producing comprehensive two-dimensional
      separations. A series of calculations have been performed to determine how
      sampling period, duty cycle, and sampling phase affect (1) the fraction of
      material transferred from the primary column to the secondary column, (2) the
      accuracy of primary retention time determination, and (3) the effective peak
      width along the primary retention axis. The results demonstrate that
      comprehensive two-dimensional separations can be produced without a substantial
      loss in quantitative precision and with only a moderate loss in primary column
      resolution if the sampling period is less than 1.5 times the primary peak
      standard deviation. The quantitative precision of total peak areas (for duty
      cycles less than 1.0) and primary retention time determination are rapidly
      reduced as the sampling period is increased above 1.5 times the primary peak
      standard deviation.

PMID- 12198966
TI  - Colominic acid: a novel chiral selector for capillary electrophoresis of basic
      drugs.
AB  - We introduced colominic acid as a new chiral selector for capillary
      electrophoresis of basic drugs. Use of a low concentration phosphate buffer
      containing this polysaccharide and a Polybrene/colominic acid double coated
      capillary allowed excellent separation of the enantiomers of primaquine,
      chloroquine and tryptophan. Other drugs giving partial enantioseparation include
      laudanosine and salbutamol. Capillary coating with Polybrene followed by
      colominic acid eliminated the problems of peak tailing and low reproducibility of
      migration time in uncoated capillaries. The optimum pH was in the acidic region
      but varied among drugs. A low capillary temperature of 16 degrees C and a
      colominic acid concentration of 9 w/v% are recommended for practical analysis of
      these drugs. Colominic acid preparations having higher molecular masses gave
      better enantioseparation, and N-acetylneuraminic acid, the component
      monosaccharide, did not give any enantioseparation.

PMID- 12198967
TI  - Electrophoretic studies on the chelating tendency of bioactive sulphur-containing
      amino acids. The metal-methylcysteine-cysteine system.
AB  - Stability constants of binary Fe(III)-methylcysteine, Cr(III)-methylcysteine and
      mixed Fe(III)-methylcysteine-cysteine, Cr(III)-methylcysteine-cysteine complexes
      have been determined by paper electrophoresis at 0.1 M ionic strength and a
      temperature of 35 degrees C. The stability constants of Fe(III)-methylcysteine
      cysteine and Cr(III)-methylcysteine-cysteine mixed complexes were found to be
      6.00 +/- 0.07 and 5.05 +/- 0.15 (logarithm of stability constant values),
      respectively.

PMID- 12198968
TI  - Purification of icariin from the extract of Epimedium segittatum using high-speed
      counter-current chromatography.
AB  - Icariin was purified from the extract of Epimedium segittatum by high-speed
      counter-current chromatography with a two-phase solvent system composed of n
      hexane-n-butanol-methanol-water (1:4:2:6, v/v). We used two multilayer coil
      planet centrifuges with different capacities. A 300 mg amount of the extract was
      separated using a semipreparative instrument equipped with a 230-ml capacity
      column to yield 103 mg of icariin at 86.2% purity. An 8 g amount of the extract
      was separated with a large preparative instrument equipped with a 2460-ml
      capacity column to produce 2.45 g of icariin at 85.7% purity. From these
      fractions over 98% pure icariin was obtained by recrystallization with water.

PMID- 12198970
TI  - Analysis of diffusion models for protein adsorption to porous anion-exchange
      adsorbent.
AB  - The ion-exchange adsorption kinetics of bovine serum albumin (BSA) and gamma
      globulin to an anion exchanger, DEAE Spherodex M, has been studied by batch
      adsorption experiments. Various diffusion models, that is, pore diffusion,
      surface diffusion, homogeneous diffusion and parallel diffusion models, are
      analyzed for their suitabilities to depict the adsorption kinetics. Protein
      diffusivities are estimated by matching the models with the experimental data.
      The dependence of the diffusivities on initial protein concentration is observed
      and discussed. The adsorption isotherm of BSA is nearly rectangular, so there is
      little surface diffusion. As a result, the surface and homogeneous diffusion
      models do not fit to the kinetic data of BSA adsorption. The adsorption isotherm
      of gamma-globulin is less favorable, and the surface diffusion contributes
      greatly to the mass transport. Consequently, both the surface and homogeneous
      diffusion models fit to the kinetic data of gamma-globulin well. The adsorption
      kinetics of BSA and gamma-globulin can be very well fitted by parallel diffusion
      model, because the model reflects correctly the intraparticle mass transfer
      mechanism. In addition, for both the favorably bound proteins, the pore diffusion
      model fits the adsorption kinetics reasonably well. The results here indicate
      that the pore diffusion model can be used as a good approximate to depict protein
      adsorption kinetics for protein adsorption systems from rectangular to linear
      isotherms.

PMID- 12198971
TI  - Combination of linear solvent strength model and quantitative structure-retention
      relationships as a comprehensive procedure of approximate prediction of retention
      in gradient liquid chromatography.
AB  - Quantitative structure-retention relationships (QSRR) combined with the linear
      solvent strength (LSS) model are demonstrated to provide approximate predictions
      of gradient reversed-phase high-performance liquid chromatography (HPLC)
      retention time for any structurally defined analyte on a once characterized
      column. The approach requires at first the determination of retention times for a
      predesigned model series of 15 analytes in two gradient runs. Then by employing
      the LSS theory a given HPLC system of interest is quantitatively characterized.
      Structure of the model analytes is next described quantitatively by means of
      three structural descriptors from standard molecular modeling: total dipole
      moment, electron excess charge of the most negatively charged atom and water
      accessible molecular surface area. With those data the general QSRR equations are
      derived which describe gradient retention times of the model analytes in the
      specific column/eluent system. Having now the structural descriptors for any
      analyte to be chromatographed in such a characterized HPLC system, one employs
      respective general QSRR equations to calculate its expected gradient retention
      time at given gradient conditions by means of appropriate LSS equations.
      Additionally, the chromatographic parameters log kw and S can be calculated and
      retention coefficients corresponding to chosen isocratic conditions evaluated.
      The approach provides retention predictions which can be treated as a first
      approximation of actual data. Predictions are not yet precise enough for
      practical separation purposes but can be of use in rational modification of
      analytical conditions aimed at optimization of separations.

PMID- 12198969
TI  - Preparative isolation and purification of calycosin from Astragalus membranaceus
      Bge. var. mongholicus (Bge.) Hsiao by high-speed counter-current chromatography.
AB  - Calycosin was purified from an ethyl acetate extract of the root of Astragalus
      membranaceus Bge. var. mongholicus (Bge.) Hsiao by high-speed counter-current
      chromatography. The separation was performed in two steps with a two-phase
      solvent system composed of n-hexane-chloroform-methanol-water (1:3:3:2, v/v).
      From 200 mg of the crude extract, 14.8 mg of calycosin was obtained at over 99%
      purity as determined by HPLC analysis, and its chemical structure was confirmed
      by MS, 1H and 13C nuclear magnetic resonance.

PMID- 12198972
TI  - Application of the general rate model and the generalized Maxwell-Stefan equation
      to the study of the mass transfer kinetics of a pair of enantiomers.
AB  - The general rate model of chromatography can be coupled with the generalized
      Maxwell-Stefan equation that describes the surface diffusion flux. The resulting
      model is useful to describe the behavior of two enantiomers during their
      separation on chiral phases, cases in which the mass transfer kinetics is known
      to be sluggish. A case in point is the modeling of the elution profiles of the
      racemic mixture of the two enantiomers of 1-phenyl-1-propanol on cellulose
      tribenzoate coated on silica, a popular chiral stationary phase. The competitive
      equilibrium isotherm behavior of the two enantiomers on the chiral stationary
      phase was described using the competitive Toth isotherm model. An excellent
      agreement between the experimental and the calculated profiles was observed in
      the whole range of experimental conditions investigated, at low and high column
      loadings.

PMID- 12198973
TI  - Chromatographic characteristics of cholesterol-imprinted polymers prepared by
      covalent and non-covalent imprinting methods.
AB  - Cholesterol-imprinted polymers were prepared in bulk polymerization by the
      methods of covalent and non-covalent imprinting. The former involved the use of a
      template-containing monomer, cholesteryl (4-vinyl)phenyl carbonate, while the
      latter used the complexes of template and functional monomer, methacrylic acid or
      4-vinylpyridine prior to polymerization. Columns packed with these molecularly
      imprinted polymers (MIPs) were all able to separate cholesterol from other
      steroids. For different combinations of cholesterol and beta-estradiol
      concentrations in a total of 1 g/l, the peak retention times for both compounds
      were nearly constant. The adsorption capacity for cholesterol onto the MIPs was
      found to significantly depend on the use of functional monomers, but the
      selectivity factors were only slightly different from each other at 2.9 to 3.2
      since the separation was all based on the specific binding of cholesterol to
      recognition sites formed on the imprinted polymers. The capacity factors for
      cholesterol were determined to be 3.5, 4.0 and 3.1, respectively, for covalently
      imprinted, 4-vinylpyridine-based, and methacrylic acid-based non-covalently
      imprinted polymers. However, the covalently imprinted polymer was found to have a
      higher adsorption capacity for cholesterol and about fivefold higher
      chromatographic efficiency for cholesterol separation, in comparison with non
      covalently imprinted polymers. The use of covalent imprinting significantly
      reduced the peak broadening and tailing. This advantage along with constant
      retention suggests that the covalently imprinted polymer has potential for
      quantitative analysis.

PMID- 12198974
TI  - Development of a high-performance liquid chromatography carbon column based
      method for the fractionation of dioxin-like polychlorinated biphenyls.
AB  - A method to separate polychlorinated biphenyls (PCBs) by using high-performance
      liquid chromatography (HPLC) was developed. The HPLC column was packed with Amoco
      PX-21 activated carbon dispersed on octadecylsilane (ODS). The separation was
      carried out by gradient elution with n-hexane-dichloromethane and toluene in the
      forward direction followed by reversed elution with toluene. The results show
      that this HPLC method is useful for the separation of PCBs according to the
      number of substituted ortho chlorine atoms attached to the biphenyl structure.
      Average recoveries for a number of individual di-ortho PCBs, mono-ortho PCBs, and
      non-ortho PCBs in three selected elution windows were 97, 92, and 96%,
      respectively. Clophen A50, a herring sample, and a cod liver oil sample were
      fractionated on the column and the analytical results are compared with data from
      the literature. The method presented here is useful for quantitative separations
      of mono-ortho PCBs as well as non-ortho PCBs which have been assigned toxic
      equivalency factors by the World Health Organisation.

PMID- 12198975
TI  - Determination of metribuzin and major conversion products in soils by microwave
      assisted water extraction followed by liquid chromatographic analysis of
      extracts.
AB  - A multiresidue method developed for the analysis of metribuzin and its major
      conversion products, deaminometribuzin (DA), diketometribuzin (DK) and
      deaminodiketometribuzin (DADK), in soils is presented. The method is based on
      microwave-assisted water extraction (MAWE) of soils using 10 mM phosphate buffer,
      pH 7 as extractant and analysis of aqueous extracts by HPLC-diode array
      detection. MAWE operational parameters were optimized with respect to extraction
      efficiency of the target compounds from soils with 1.5 and 3.5% organic matter
      content. Recoveries of all solutes above 80% were obtained from soils with 1.5%
      organic matter content; respective LOD and LOQ levels were determined at 5 and 10
      micrograms/kg. In soils with organic matter content 3.5%, recoveries of all
      solutes were lower (< 70%) and the respective LOD and LOQ values were determined
      at 10 and 50 micrograms/kg. However, recoveries of fresh and aged residues, the
      latter weathered under cold storage conditions, were not statistically different
      for both types of soils.

PMID- 12198976
TI  - High-performance liquid chromatography--mass spectrometry and electron-capture
      dissociation tandem mass spectrometry of osteocalcin. Determination of gamma
      carboxyglutamic acid residues.
AB  - Two mass spectrometry methods, high-performance liquid chromatography combined on
      line with electrospray ionization mass spectrometry (HPLC-ESI-MS) and electron
      capture (EC) dissociation tandem mass spectrometry (MS-MS), were applied for
      structural analysis of bovine and human osteocalcins. Osteocalcin contains gamma
      carboxyglutamic acid (Gla) residues, which bind metal ions, among its amino
      acids. Ethylenediaminetetraacetic acid (EDTA) was added to all samples in order
      to chelate bound metal ions. After elimination of interfering metal ions MS
      spectra became uncomplicated to interpret. EDTA is incompatible with ESI and it
      was removed from samples using either on-line HPLC or micropurification method.
      The number of Gla residues varies in osteocalcin. These subforms, which contain
      different amounts of Gla residues, were separated using the HPLC-ESI-MS method.
      In order to determine locations of Gla residues in human osteocalcin, which
      contained two Gla residues, dissociation MS-MS method was successfully applied.

PMID- 12198978
TI  - Orthodontic therapy.

PMID- 12198977
TI  - Treating periodontal disease.

PMID- 12198979
TI  - A second opinion.

PMID- 12198980
TI  - Dental implant success.

PMID- 12198981
TI  - Amalgam restorations.

PMID- 12198982
TI  - In your dental practice, is dental amalgam still the restorative material of
      choice?

PMID- 12198984
TI  - Maryland adults' perspectives on oral cancer prevention and early detection.
AB  - OVERVIEW: In any given 12-month period, Maryland ranks 27th among all states and
      the District of Columbia in estimated new cases of oral cancer. The state also
      has the seventh highest overall mortality rate for oral cancer. Because of
      earlier research indicating that Maryland adults had little knowledge and many
      misconceptions about oral cancer, the authors undertook a study to obtain in
      depth information from Maryland adults 40 years of age or older on oral cancer,
      oral cancer examinations and factors associated with having an oral cancer
      examination. METHODS: The authors conducted a qualitative descriptive study using
      information gathered from three focus groups consisting of nine, 10 and seven
      adults respectively, and which met at two locations. The authors hired a private
      focus group research firm, which randomly selected participants from a telephone
      list of local residents. A professionally trained moderator conducted all focus
      groups using a semistructured interview guide. RESULTS: Participants were struck
      by the fact that they rarely hear about this type of cancer. Many said that they
      never had had an oral cancer examination and did not know there was such a thing.
      Many participants also reported that they likely would be more comfortable
      discussing oral cancer with their physicians than with their dentists.
      CONCLUSIONS: These findings provide additional in-depth insights to earlier work
      about Maryland adults' oral cancer knowledge, opinions and practices. The state
      plans to use this information to develop educational materials and interventions
      for the public to promote oral cancer prevention and early detection in Maryland.
      CLINICAL IMPLICATIONS: Extensive public education about oral and pharyngeal
      cancers should be provided in dental offices and clinics, as well as in mass
      media of all types. More clinicians should include comprehensive oral cancer
      screenings in their oral examinations, and they should explain to patients what
      they are doing when they provide these screenings.

PMID- 12198983
TI  - Selecting new drugs for pain control: evidence-based decisions or clinical
      impressions?
AB  - BACKGROUND: Selecting drugs for pain control in dentistry should be based on
      scientific research rather than clinical impressions. This article highlights the
      scientific attributes of analgesic medications that make them practical for
      treating postoperative dental pain. METHODS: This article is based on a review of
      the general characteristics of double-blind, controlled clinical studies compared
      with clinical observation in dental practice. The literature reviewed included
      all recent published clinical studies in refereed journals pertinent to the use
      of rofecoxib, a selective cyclo-oxygenase-2, or COX-2, inhibitor, in treating
      postoperative dental pain. The author focuses on some pharmacokinetic parameters
      of this agent as they compare with those of nonselective COX-2 inhibitors used to
      control dental pain. (The other selective COX-2 inhibitors, celecoxib and
      valdecoxib, do not carry label indications for short-term management of
      postoperative pain.) RESULTS: The findings of this literature review show that
      the COX-2-selective inhibitor rofecoxib is no more effective than conventional,
      nonselective, nonsteroidal anti-inflammatory drugs, or NSAIDs, for the relief of
      postoperative dental pain. Rofecoxib does, however, have the disadvantage of
      requiring rescue medication from a different class of drugs in a significant
      number of patients. CONCLUSIONS: The currently available COX-2-selective
      inhibitors do not replace conventional NSAIDs for the short-term treatment of
      postoperative dental pain. However, they are useful for treating chronic pain
      conditions because they produce fewer adverse effects when taken long-term than
      do conventional NSAIDs. CLINICAL IMPLICATIONS: Selecting drugs for the short-term
      relief of postoperative dental pain should be based on a careful assessment of
      all relevant pharmacological characteristics of a given agent, especially those
      related to maximum dosage, duration of action and efficacy.

PMID- 12198985
TI  - Oral cancer knowledge, risk factors and characteristics of subjects in a large
      oral cancer screening program.
AB  - BACKGROUND: Screening people who are at high risk of developing oral cancers is a
      promising tool for decreasing morbidity and mortality attributable to this
      cancer. METHODS: A consortium led by the New York University College of Dentistry
      conducted a three-day oral cancer screening during June 1999. As part of the
      screening intake, the authors conducted a survey to assess the sociodemographic
      characteristics, level of knowledge of risk factors and predictors of oral cancer
      awareness among the subjects. The authors performed bivariate and multivariate
      analyses using two indicators of oral cancer awareness as dependent variables.
      RESULTS: The 803 subjects were racially and ethnically diverse, 66 percent were
      40 years of age or older, 43 percent had a history of smoking, and 9 percent were
      likely to have had a history of alcohol abuse. Race/ethnicity, education level
      and knowledge of risk factors for oral cancer were predictors of awareness of an
      oral cancer examination, whereas only knowledge and possible history of alcohol
      abuse were predictors of having a history of examinations. CONCLUSIONS: This
      screening program attracted a diverse sample of people at high risk of developing
      oral cancer due to smoking and likely history of alcohol abuse. Consistent with
      other national and international studies, the authors found a lack of knowledge
      of the risk factors associated with oral cancer and a low rate of histories of
      oral cancer examinations among the subjects. CLINICAL IMPLICATIONS: Oral cancer
      screening programs represent potential opportunities not only for early detection
      of oral cancer but to raise awareness and educate the public about the disease.

PMID- 12198986
TI  - Desmoplastic variant of ameloblastoma: report of two cases and review of the
      literature.
AB  - BACKGROUND: The desmoplastic ameloblastoma exhibits important differences in
      anatomical distribution, histologic appearance and radiographic findings compared
      with the classic type of ameloblastoma. The purpose of this article is to assist
      the dental community in better understanding this variation in odontogenic tumor.
      CASE DESCRIPTIONS: The authors present two cases of desmoplastic variant of
      ameloblastoma localized in the anterior portion of the jaw. The tumors were
      expansile, destructive and painless. The radiographic findings showed diffuse,
      mixed (radiopaque/radiolucent) lesions with cortical bone destruction. Block
      excision was performed in both cases. Follow-up examination one and two years
      later disclosed no recurrence of tumor. CLINICAL IMPLICATIONS: The desmoplastic
      variant of ameloblastoma tends to infiltrate between bone trabeculae. Curettage
      leaves islands of tumor within bone, which later manifest as recurrences.
      Therefore, block excision is the most widely used treatment to avoid recurrence.

PMID- 12198987
TI  - Incidence of tooth sensitivity after home whitening treatment.
AB  - BACKGROUND: A potential side effect of dentist-dispensed home tooth-whitening
      systems is tooth sensitivity. The authors conducted a randomized prospective
      double-blind study to determine the incidence of tooth sensitivity after home
      whitening treatment. METHODS: Fifty adult subjects used a gel containing 15
      percent carbamide peroxide and 0.11 percent fluoride ion; an additional 50 adult
      subjects used a placebo gel daily for four weeks. Each subject's plaque index
      score, gingival recession status, caries status, current dentifrice and smoking
      history were recorded at baseline. The researchers evaluated sensitivity weekly
      by interview for four weeks. RESULTS: Fifty-four percent of subjects in both test
      and control groups reported mild sensitivity; 10 percent of test subjects and 2
      percent of control subjects reported moderate sensitivity; 4 percent of test
      subjects and no control subjects reported severe sensitivity. Sensitivity
      decreased with time; by the second week, no severe sensitivity was reported, and
      by the fourth week, no moderate sensitivity was reported. The authors found a
      statistically significant positive correlation between reported sensitivity and
      gingival recession. They found no statistically significant correlations between
      sensitivity and any of the other recorded parameters. CONCLUSIONS: Mild tooth
      sensitivity can be expected in approximately one-half of patients who undergo
      home whitening treatment using the gel studied. Approximately 10 percent of
      patients may experience moderate sensitivity, and 4 percent of patients may
      experience severe sensitivity for one to two weeks. Patients with gingival
      recession appear more likely to experience tooth sensitivity during home
      whitening treatment. CLINICAL IMPLICATIONS: Patients considering home whitening
      treatment should be advised that mild tooth sensitivity is a common side effect
      and that severe tooth sensitivity occasionally occurs. If gingival recession is
      present, the probability of tooth sensitivity increases, and tooth sensitivity
      tends to decrease as treatment progresses.

PMID- 12198988
TI  - The use of low-molecular-weight heparins in outpatient oral surgery for patients
      receiving anticoagulation therapy.
AB  - BACKGROUND: When planning oral surgery, dentists occasionally will have patients
      who first need to have their anticoagulation regimen altered. To minimize the
      side effects and not adversely affect the patient's health, therapeutic
      anticoagulation should be interrupted for as short a time as possible. Low
      molecular-weight heparins, or LMWHs, recently have emerged as an alternative in
      the management of patients whose anticoagulant status should not be modified for
      lengthy periods. CASE DESCRIPTION: A 72-year-old man, who had a history of deep
      venous thrombosis, needed to have 19 teeth extracted and an alveoloplasty
      performed. An LMWH was substituted for warfarin a few days before surgery, and it
      was withheld from the patient for only a few hours the day of the surgery.
      CLINICAL IMPLICATIONS: LMWHs are administered on an outpatient basis and do not
      require hospitalization, as does unfractionated heparin. As a result, they are
      more cost-effective and offer greater convenience than heparin therapy. Depending
      on the procedure and the degree to which patients are medically compromised,
      dentists may not feel comfortable treating patients who continuously receive
      anticoagulation therapy. As a result, patients' physicians may prescribe LMWH
      injections to be administered by patients, family members or caregivers to more
      safely manage the patients' care during oral surgery. As part of the health care
      team, dentists must be familiar with LMWH and its use to help guide patients
      safely through treatment.

PMID- 12198989
TI  - Treatment of patients who have type 1 diabetes mellitus: physiological
      misconceptions and infusion pump therapy.
AB  - BACKGROUND: This article reviews the unique physiology of patients who have type
      1 diabetes mellitus (insulin-dependent diabetes mellitus, or IDDM); allays some
      common physiological misconceptions; and updates dental practitioners on the
      emerging technology of insulin infusion pump therapy, now available to patients
      who have type 1 diabetes mellitus. DESCRIPTION: The authors review the physiology
      of stress and describe the dawn phenomenon. They also describe insulin infusion
      pump therapy, as well as its advantages and disadvantages, to familiarize
      dentists with new technologies in caring for patients who have diabetes.
      Emergencies that may present themselves as a result of these advances in
      biotechnology are discussed. CLINICAL IMPLICATIONS: Dental practitioners who
      treat patients who have IDDM need to have a solid foundation in the basic medical
      sciences and emerging biomedical technology as they each relate to diabetes.
      Practitioners must become familiar with infusion pump therapy, not only for cases
      of medical emergencies, but also to customize treatment for patients who have
      diabetes. Practitioners also need to remain up to date in the rapidly changing
      realm of caring for people who have diabetes.

PMID- 12198990
TI  - The dental work force in Wisconsin: ten-year projections.
AB  - BACKGROUND: The national dentist-to-population ratio is expected to decline
      during the next decade. The Wisconsin Dental Association undertook a study to
      determine the impact of this decline on the future supply of and demand for
      dental care in Wisconsin. METHODS: Using state and national data, the researchers
      estimated the number of dentists leaving and entering the state for the years
      2001 through 2010. Then, using multivariate regression equations, the researchers
      estimated expected changes in dentists' productivity, the growth of the Wisconsin
      population and increases in utilization of dental services for the next 10 years.
      From these data, they determined the number of dentists needed in 2010 to
      maintain the current level of access. They assessed several strategies for
      increasing the number of dentists in the state. RESULTS: Wisconsin will have 297
      fewer dentists in 2010 than it did in 2000. However, with increases in dentists'
      productivity of 1.8 percent per year, a slowly growing Wisconsin population (0.42
      percent per year) and modest increases in utilization (0.82 percent per year),
      Wisconsin will need only 194 additional dentists to maintain current levels of
      access to care. The authors examined several options for increasing the number of
      dentists and their productivity, including increasing the number of Wisconsin
      (vs. out-of-state) students enrolled at Marquette University School of Dentistry,
      Milwaukee, employing more auxiliaries and using risk-based scheduling for recall
      patients. CONCLUSIONS: Wisconsin will have fewer dentists in 2010 than in 2000,
      but current levels of access can be maintained by implementing modest changes in
      the selection of dental students at Marquette, in the use of dental auxiliaries
      and in patient scheduling. CLINICAL IMPLICATIONS: With the national dentist-to
      population ratio declining, each state should assess how its supply and demand
      for dental care will change in the next 10 years. If substantial supply-and
      demand imbalances exist, options for correcting the imbalances need to be
      considered.

PMID- 12198991
TI  - A prosthesis for achieving dry-field isolation of molars with short clinical
      crowns.

PMID- 12198992
TI  - Future of dentistry: dental practice issues. Interview.

PMID- 12198993
TI  - Supreme Court upholds Illinois law requiring independent review of some HMO
      coverage decisions.

PMID- 12198994
TI  - Solving the frustrations of crown cementation.
AB  - Restoration cementation is a routine procedure, but it commonly is accomplished
      improperly. In this article, I have discussed several of the most frequently
      occurring problems with restoration cementation and have made suggestions about
      how to prevent them.

PMID- 12198995
TI  - Bone-grafting materials. Their uses, advantages and disadvantages.

PMID- 12198996
TI  - For the dental patient.... Tooth-colored fillings.

PMID- 12198997
TI  - Minimal acceptable care as a vital component to Missouri's trauma system.
AB  - Immediate attention to life-threatening injuries and expeditious transfer of
      major and complex wounds to tertiary care trauma centers are the cornerstones of
      any trauma system. Rapid assessment and "minimalization" of care should be the
      buzz-word of rural (Level III) and suburban (Level II) trauma centers in order to
      provide quickest treatment of injuries by timely referral of patients for
      definitive attention. This concept is called minimal acceptable care and may
      serve to improve patient outcome by reducing the interval to ultimate treatment
      and avoidance of duplication of services.

PMID- 12198998
TI  - Factors associated with screening for colorectal cancer in a population-based
      sample.
AB  - The results of this study shed light on groups of people with shared
      characteristics that may be at higher risk for colorectal cancer incidence and
      mortality based on non-compliance with recommended screening tests. The study
      showed Missouri has a slightly different pattern of colorectal cancer screening
      prevalence than the US. Public health efforts need to promote colorectal
      screening to at-risk Missourians, and should consider strategies that encourage
      jointly screening for various chronic diseases.

PMID- 12198999
TI  - Does payment improve follow-up of pelvic inflammatory disease?
AB  - In order to determine whether a monetary incentive would increase clinic follow
      up rates in patients treated for pelvic inflammatory disease (PID) in the
      emergency department (ED), a randomized, prospective study was undertaken.
      Comparison was made between groups offered $5.00 plus transportation costs and
      groups offered transportation costs only. Follow-up rates were low in the
      experimental and control groups, and not statistically different. We conclude
      that a $5.00 incentive does not increase follow-up rates after ED treatment of
      PID.

PMID- 12199000
TI  - Pediatric research: the role of the institutional review board.

PMID- 12199001
TI  - Workforce development: a quick fix or a collaborative process?

PMID- 12199003
TI  - A multicentre retrospective audit of outcome of patients undergoing curative
      resection for rectal cancer.
AB  - AIM: This study describes the outcome of patients with rectal cancer treated in
      four New Zealand public hospitals before the advent of specialised colorectal
      units in order to provide a baseline against which any changes in management can
      be measured. METHODS: A retrospective review of case notes of patients who
      underwent resection of rectal cancer with curative intent over a period of 7-10
      years up to 1995 in Christchurch, Wellington, Nelson, and Masterton Public
      Hospital's, was undertaken. Patients were identified from hospital records using
      a combination of methods (pathology data bases, clinical case mix data, operating
      logs and audit data). Metastatic disease was considered to be present if
      confirmed on histology or the clinical course of the patient was consistent with
      metastatic disease. Patients were excluded if there was perioperative evidence of
      metastatic disease or if they had transanal excision. Previously published
      results from Auckland and Dunedin Hospitals are compared. RESULTS: 524 patients
      with rectal cancer were identified who had undergone surgery with curative intent
      in the four hospitals. The overall permanent stoma rate was 37%. The overall 30
      day mortality was 2.9%, five-year survival was 63% and local recurrence at five
      years was 26%. CONCLUSION: While low perioperative mortality and good long-term
      survival were achieved, there were high rates of local recurrence. These data are
      a baseline against which the impact of new approaches to curative resection for
      rectal cancer can be measured.

PMID- 12199002
TI  - Geographically separate outbreaks of shigellosis in Auckland, New Zealand, linked
      by molecular subtyping to cases returning from Samoa.
AB  - AIM: To investigate simultaneous outbreaks of Shigella sonnei gastroenteritis
      occurring in February 2001 at a health camp for socially deprived children and an
      elderly care facility. METHODS: Those with symptoms were interviewed using a
      standardised questionnaire. Cases were defined as having at least three loose
      stools over a 24 hour period and stool samples requested. A case-control study
      investigating routes of transmission was performed at the health camp.
      Environmental investigations of food safety and hygiene were conducted at each
      facility. RESULTS: At the camp, 15 (37%) students and 15 (28%) staff met case
      criteria. Contact with human faeces (OR 4.0; 95% confidence interval 1.0-16.3; p
      = 0.05) and, for staff, eating camp food (OR 6.9; 1.0-5.0; p = 0.06) were shown
      to be independent risk factors for illness. At the elderly care facility, four
      (19%) residents and four (25%) staff met case criteria. Molecular subtyping
      confirmed that the outbreaks were related to each other and to other cases in
      travellers returning from Samoa to Auckland and other New Zealand cities over a
      four month period. CONCLUSION: Molecular subtyping is of considerable use in
      communicable disease investigation, providing strong evidence for links between
      outbreaks. With expanded technological capability, New Zealand could perform
      routine molecular subtyping of selected organisms to improve the detection and
      the investigation of regional and inter-regional outbreaks of infection.

PMID- 12199004
TI  - Leg ulcers in New Zealand: age at onset, recurrence and provision of care in an
      urban population.
AB  - AIM: To describe the age at onset, recurrence rate, and provision of care for
      people with leg ulcers in New Zealand. METHODS: Between 1997 and 1998, people
      with current leg ulcers were identified from the North Auckland and Central
      Auckland health districts via notification from relevant health professionals and
      by self-referral. All ulcer types were investigated. Identified cases, aged
      between 40 and 99 years and on the general electoral roll, were interviewed as
      part of a case-control study. Descriptive information relating to interviewed
      cases is presented. RESULTS: 241 people with leg ulcers were interviewed. The
      average age was 75 years and almost 60% were women. The average age at ulcer
      onset was 65 years, 59% of people had recurrent ulcers, and 24% had been
      hospitalised in the last five years because of their leg ulcers. Those people
      with recurrent leg ulcers had lived with their condition for an average of
      fifteen years, with an average time to healing for their last ulcer of thirteen
      months. Treatment of this condition was largely community-based, with 136
      different treatment options employed. CONCLUSIONS: Leg ulceration remains a
      chronic and recurring condition, with substantial practice variation in terms of
      treatment. Urgent attention needs to be given to the management of leg ulcer
      patients in this country, particularly given that New Zealand has a rapidly
      ageing population.

PMID- 12199005
TI  - Mandibular advancement splint improves indices of obstructive sleep apnoea and
      snoring but side effects are common.
AB  - AIM: To assess the efficacy of a mandibular advancement splint (MAS) in the
      treatment of obstructive sleep apnoea syndrome (OSAS). METHODS: Nineteen patients
      using a MAS for symptomatic OSAS underwent polysomnography, with MAS use
      randomised to one half of the night. Indices of snoring and OSAS were compared.
      Side effects, compliance and treatment response were evaluated by questionnaire.
      RESULTS: Use of the MAS improved total respiratory disturbance index (RDI) from
      22.2 +/- 19.8 (SD) events per hour to 16.5 +/- 21.4/hr (p = 0.03), supine RDI
      (30.8 +/- 23.8/hr to 18.8 +/- 22.1/hr, p = 0.01), arousal index (25.2 +/- 18.9/hr
      to 19.3 +/- 14.2/hr, p = 0.01) and snoring intensity (52.7 +/- 4.1 to 50.7 +/-
      2.7 dB, p = 0.02) but not total snore frequency (p > 0.05). Using
      polysomnographic criteria, MAS treatment was completely successful in four (21%)
      patients, partially successful in ten (52.6%) and a failure in five (26.3%).
      Treatment over a median of 6.5 weeks (range 2-48) was perceived as beneficial by
      ten of eleven partners. Fifteen patients (79%) reported side effects, 9 (46%) did
      not use the device every night and four (21%) used the device less than three
      nights per week. CONCLUSION: The use of the MAS resulted in significant
      reductions in indices of OSAS and snoring. However, a significant number of
      patients had difficulty tolerating and regularly using the device.

PMID- 12199006
TI  - Diaphragm disease of the large bowel due to non steroidal anti inflammatory
      drugs.

PMID- 12199007
TI  - Hodgkin's disease following methotrexate therapy for rheumatoid arthritis.

PMID- 12199008
TI  - References in medical advertising--too often a blend of fact and fiction?

PMID- 12199009
TI  - Specialisation within the speciality of general surgery; can the potential
      advantages be realised?

PMID- 12199010
TI  - Challenges for District Health Boards as needs assessors.
AB  - DHBs face the foregoing challenges in the current and future environment, as they
      take on democratic representation for the population, particularly in health
      needs assessment, consultation, prioritization and health service purchasing.
      Need and objectives must be clearly defined at an early stage in the context of
      resource constraints and timeframes that will challenge the ability of Boards to
      conduct needs assessments. Consultation with the community and other, expert
      groups must inform needs assessments. But it is not clear how the prioritization
      process will work, particularly regarding the ability of local agendas for
      purchasing of health services that complement the national agenda. Recent health
      crises have shown that DHBs, without Government support, cannot easily meet such
      challenges in the new decentralised environment. Consideration must therefore be
      given to how these identified challenges for DHBs as needs assessors can best be
      met.

PMID- 12199011
TI  - Ending the patient relationship.

PMID- 12199012
TI  - Thiopurine methyltransferase activity and azathioprine.

PMID- 12199013
TI  - Cultural sensitivity.

PMID- 12199014
TI  - A cheap medication for smoking cessation.

PMID- 12199016
TI  - Electronic communication with general practice.

PMID- 12199015
TI  - Chairman of Canterbury DHB comments on Auckland editorial.

PMID- 12199018
TI  - Cancer flourishes.

PMID- 12199019
TI  - Asthma: more than mites?

PMID- 12199020
TI  - Simple, effective ear syringing.

PMID- 12199021
TI  - Conduct unbecoming inappropriate examination.

PMID- 12199022
TI  - Conduct unbecoming--obstetric care.

PMID- 12199023
TI  - Taking care of teens.

PMID- 12199024
TI  - The challenge of adolescence.

PMID- 12199025
TI  - Dealing with diabetes.

PMID- 12199026
TI  - Not for adults only.

PMID- 12199027
TI  - Plugging gaps in adolescent health care.

PMID- 12199028
TI  - The evolving role of the primary care practitioner in adolescent depression
      screening and treatment.
AB  - Increasing rates of depression in adolescents coupled with a decrease in the
      availability of psychiatric care has created the need for primary care physicians
      to become proficient in the screening and first-line treatment of mental and
      emotional disorders in their adolescent patients. This paper reviews the
      epidemiology and natural course of depression in adolescents, the health care
      climate changes leading to a decrease in the availability of psychiatric care in
      the community, and the role of the primary care practitioner in screening for and
      treating depression in the adolescent patient. In addition, screening tools and
      specific pharmacotherapeutic approaches are discussed.

PMID- 12199029
TI  - Health care of youth in corrections.
AB  - The number of juveniles in correctional facilities is growing. These youth tend
      to have significant medical and mental health problems, yet they are underserved
      with respect to health care. Health care providers can work to improve the health
      status of incarcerated youth by pushing for improved funding of and standards for
      their health care and for their increased access to care while they are in
      correctional facilities and after they are released. This article presents a
      summary of statistics about the rates of youth incarceration and about the health
      status of such youth. It also offers recommendations for improving the health
      care of juveniles involved with the justice system.

PMID- 12199030
TI  - Integrated planning for disaster. A model for Minnesota hospitals.

PMID- 12199031
TI  - Relocation requires the three Ps: planning, patience, and persistence.

PMID- 12199032
TI  - Approach to chronic illness: the physician's plight.

PMID- 12199033
TI  - Physicians square off against powerful opponent.

PMID- 12199034
TI  - A voice for teens.

PMID- 12199035
TI  - Truth and memory.

PMID- 12199036
TI  - Avoiding inappropriate medication use by the elderly: a stepwise approach.

PMID- 12199037
TI  - [What is a "true" threatened premature labor?].

PMID- 12199038
TI  - [Alternatives to amniocentesis for maternal age].
AB  - Screening strategies of Down's syndrome should be re-evaluated. Amniocentesis for
      advanced maternal age has been proposed in the 70's because no other screening
      test was available. Maternal serum screening and first trimester nuchal
      translucency are now well validated, including in women over 38. The sequential
      and independent use of different screening tests leads to a dramatic increase of
      the false positive rate and thus of iatrogenic fetal losses. Maternal age remains
      the major risk factor for chromosomal anomalies, but it should be included in
      risk calculation strategies (ideally combining serum screening and nuchal
      translucency), and not taken as an isolated information. These screening
      strategies require strict quality control and audit, which is currently better
      achieved with serum screening than ultrasound screening. A complete information
      about Down's syndrome screening strategies should be given to women, regardless
      of their age, and their personal choice should be respected. For women of
      advanced maternal age, a policy of selective rather than routine amniocentesis is
      likely to reduce the risk of iatrogenic fetal loss and yet to allow for a
      reasonable sensitivity.

PMID- 12199039
TI  - [Marfan syndrome and pregnancy. Apropos of 4 cases].
AB  - OBJECTIVES: To create a follow-up protocol for pregnant patients with Marfan
      syndrome. PATIENTS AND METHODS: We retrospectively reviewed the charts of
      patients who delivered in the Jeanne de Flandre University Hospital between June
      1996 and June 1999. Four pregnant patients with Marfan syndrome were identified.
      RESULTS: Three of these patients had Bentall procedure. One of them had vaginal
      delivery and the two others underwent cesarean section. One of these two patients
      developed aortic valve thrombus at 14 weeks of amenorrhea. The fourth patient did
      not have surgery and had two vaginal deliveries. DISCUSSION: According to our
      results and after reviewing literature pregnant patients with Marfan syndrome
      were divided into two groups. The 1st group was comprised of patients who
      underwent Bentall procedure. The 2nd one was comprised of patients who did not
      undergo any surgical procedure. The possibility of vaginal delivery for patients
      who underwent Bentall procedure (one case) and the interest of Propanolol and
      anticoagulant treatment are emphasized. CONCLUSION: The multivariant approach of
      pregnant patients with Marfan syndrome is stressed out with special reference to
      the potential complications of this syndrome such as aortic dissection and to the
      problems related to the anticoagulant treatment.

PMID- 12199040
TI  - [Insertion of a sub-urethral sling through the obturating membrane for treatment
      of female urinary incontinence].
AB  - OBJECTIVE: The use of a TVT device has been for a few years the operation most
      often performed to treat female urinary incontinence. One of the most frequent
      complications of this surgery is bladder perforation. MATERIAL AND METHODS: To
      prevent this complication we use the way initially suggested by Delorme, in which
      the two ends of the sling were passed through the obturating membrane and the
      muscles which cover it, by circumventing the ischiopubic bone with Emmet needle
      introduced from outside to inside. RESULTS: No bladder perforation was noted
      among the first 71 operated patients. For the first 68 patients re-examined 6 to
      12 weeks after the surgery, two patients had improved and 64 were totally cured.
      CONCLUSION: The effectiveness of this method is the same as that of the
      traditional method.

PMID- 12199041
TI  - [Prognosis and fertility after conservative treatment for ovarian tumors of
      limited malignity: review of 68 cases].
AB  - The aim of this retrospective study was to evaluate the rate of recurrence and
      the reproductive outcome after surgical conservative treatment of low malignant
      ovarian tumors (LMOT). MATERIAL AND METHODS: Sixty-eight patients with 50 Stage I
      LMOT and 18 LMOT with peritoneal implants treated conservatively at institut
      Gustave-Roussy, between January 1969 and December 2000. Fifty-nine patients had
      an unilateral adnexectomy (associated twelve times with a contralateral
      cystectomy), Seven had a bilateral cystectomy and two an unilateral cystectomy.
      Five patients received adjuvant therapy. RESULTS: With a median follow-up of 71.5
      months, 16 patients recurred and one had evolutive peritoneal disease. The
      histologic pattern of ovarian recurrences was always of borderline type. The
      histologic patterns of peritoneal recurrence was similar to those initially
      diagnosed except in one case. Peritoneal implants, exophytic tumor and serous
      type tumor were significatively associated with a higher 5-year recurrence rate.
      Recurrence was more frequent after cystectomy than unilateral adnexectomy (p =
      0.13). None of patients treated conservatively recurred under the form of ovarian
      carcinoma. None patient died of tumor. Nineteen patients experienced 26
      pregnancies: 24 were spontaneous in a median delay of 19 months. Seven infertile
      patients underwent ovarian stimulation. None recurred after infertility
      treatments. The 2-year and 5-year cumulative pregnancy rate were respectively
      41.9% and 59.8%. Four patients experienced a pregnancy after a conservative
      treatment of their recurrence. CONCLUSION: Despite a high recurrence rate,
      especially in stage II and III serous LMOT, conservative treatment of LMOT does
      not affect survival and should be considered in young patients. Such treatment is
      not advised in case of invasive peritoneal implants. Spontaneous pregnancy rate
      is good but the frequent infertility associated with these tumors can afterwards
      require ovarian stimulation. Limited number of stimulation cycles is acceptable
      in such patients.

PMID- 12199042
TI  - [Vaginal leiomyosarcoma. Apropos of 2 cases and review of the literature].
AB  - The leiomyosarcoma of the vagina is extremely rare. This paper reports two
      observations treated at the Ibn Rochd oncology center of Casablanca. The first
      patient was 32 years old, and presented a tumor of 15 cm to the detriment of the
      posterior wall of the vagina. The treatment consisted of a large exeresis of the
      tumor followed by postoperative radiotherapy. After 50 months, she is still
      alive. The second patient who was 42 years old, had a 10 cm tumor of the
      posterior wall of the vagina. A tumorectomy was realized and then the patient was
      not heard of. The evolution was marked by the appearance of pulmonary metastasis
      and a palliative chemotherapy was prescribed. This patient is deceased after 31
      months. Seventy-five cases only are described in the literature. The surgery is
      the basic treatment whereas radiotherapy is still discussed. The prognosis of
      these tumors remains linked especially to the histological rank.

PMID- 12199043
TI  - [Sex differences in adolescent care requests].
AB  - Care requests and attitude to health are different according to individual's
      gender. Epidemiological data concerning teenagers show how these differences
      rapidly occur during puberty and seem to take a part in the global sexualization
      process, specific of this period of life. Female teenagers express more important
      expectations and needs than their male fellows. They take more medical advice,
      have several complaints, take more drugs, although consulting grounds and somatic
      pathologies are appreciably the same for both sexes. Concerning mental diseases,
      the situation is even more obvious. Feminine over-representation, appearing in a
      spectacular manner during adolescence, is rather linked to the kind of disorders
      than to a purely quantitative discrepancy: depressive tendency, suicide attempts,
      eating disorders are obviously feminine, whereas boys are mainly found on the
      side of behaviour disorders, acted violence, accidents, suicide with an important
      over-mortality. These differences according to the subjects' sex should be known
      for the clinical presentation and the encountered risks assessment to improve the
      evaluation, the prevention and the taking charge of teenagers health needs.

PMID- 12199044
TI  - [Polycystic ovary syndrome: recent genetic contributions].
AB  - Polycystic ovary syndrome is the most common endocrine disorder in women of
      reproductive age. It is characterized by hyperandrogenism, chronic anovulation
      and it is often associated with hyperinsulinemia, insulin resistance and
      dyslipidaemia. The pathophysiology of polycystic ovary syndrome seems to
      implicate primary defects in ovarian steroidogenesis, influenced by environment,
      insulin action and obesity. Polycystic ovary syndrome is probably both a
      multigenetic and environmental disease. Knowing the genes of polycystic ovary
      syndrome would be helpful to develop therapeutics and prevention. Genes of
      gonadotrophins, steroid hormone synthesis and insulin resistance seem not to be
      directly involved, except perhaps the CYP 11 a gene. On the other hand,
      identification of the signal transduction pathways involved in these genes may
      provide valuable information that can be applied to other clinical manifestations
      of polycystic ovary syndrome (follicular growth arrest, insulin resistance,
      obesity and endometrial cancer...).

PMID- 12199045
TI  - [Analytical choices for biological tests in thrombotic pathology].
AB  - The knowledge of genetic and occurred risk factors allows us to propose
      laboratory investigations in patients with thromboembolism (TE) to evaluate the
      risk for recurrence. Beside coagulation inhibitor deficiencies accounting for
      less than 10% of cases, factor V Leiden and prothrombin G20210A mutations are
      found in around 30% and 10% respectively. Increased factor VIII and
      hyperhomocysteinemia resulting from interaction of genetic factors and
      environmental factor are also risk factors for TE. Finally, antiphospholipid
      antibodies, a complex family of antibodies recognizing various phospholipid or
      phospholipid binding proteins, are also associated with TE.

PMID- 12199046
TI  - [Contraception at 40].
AB  - During forty, fertility decreases but the risk of spontaneous pregnancy is not
      negligible, so contraception for forty years old women remains necessary. Several
      contraceptive methods are available: local contraception, intra-uterine devices,
      hormonal contraception. Progestogen-only pills, microdosed and continuously
      administered are to be avoided at this time of life because they can result in
      hyperestrogenic adverse events. Progestin implants are interesting if the woman
      presents contraindication with estrogens or if she is non compliant with oral
      contraceptives. Oral contraceptive use is associated with numerous benefits
      during forty: it controls properly cycles and menstruations, it decreases bone
      loss and it decreases gynaecological disorders and risk of endometrial and
      ovarian cancer... But cardiovascular risk (venous and arterial thrombo-embolism)
      remains increased, whatever oral contraceptive is used, second or third
      generation, and in spite of lower dose of ethinylestradiol, even if a trend
      towards the decrease of this risk is observed. Contraindication for one kind of
      oral contraceptive means contraindication for all oral contraceptives and
      necessarily bare respect of this. These contraindications led to contraceptive
      use of progestin with antigonadotropic activity; however if pregnane derivatives
      are devoid of any deleterious metabolic effects, they have no indication for
      contraception in their marketing authorization.

PMID- 12199047
TI  - [What is the current reasoning for cerclage? For a wide application of cerclage].

PMID- 12199048
TI  - [What is the current reasoning for cerclage? For a limited application of
      cerclage].

PMID- 12199049
TI  - [Standards, options and recommendations for the management of patients with
      invasive cancer of the cervix uterus (non-metastatic stage), abridged version].

PMID- 12199050
TI  - [Response of the members of the committee apropos the debate between J. Lansac
      and J. Cohen. Robespierre and Mirabeau. Gynecol Obstet Fertil 2002; 30: 539-43 ].

PMID- 12199051
TI  - [In response to the article by S. Uzan. What purpose does the National Counsel of
      Universities serve? Gynecol Obstet Fertil 2002; 30: 355-7].

PMID- 12199052
TI  - [In response to the article by P. This and C. Cormier. Approach of menopause in
      the woman at risk for breast cancer. Gynecol Obstet Fertil 2002; 30: 101-3].

PMID- 12199053
TI  - [In response to the article by R. Wainer. Smoking and ovarian fertility. Gynecol
      Obstet Fertil 2001; 29: 881-7].

PMID- 12199054
TI  - [In response to the article by M. Canis et al. Laparoscopy and cancer in
      gynecology. Should it be debated again or only convince the disbelievers? Gynecol
      Obstet Fertil 2001; 29: 913-8].

PMID- 12199055
TI  - [Conditional discrimination using 3-dimensional objects by a chimpanzee (Pan
      troglodytes): tests for derived stimulus relations].
AB  - A female chimpanzee (Pan troglodytes) was trained on the conditional
      discrimination task using 3-dimensional objects under a face-to-face experimental
      setting. In Experiment 1, the subject was required to pick up the correct
      comparison object, take it to the sample object, and construct a new paired
      object with a specific action. After acquisition of the task, derived stimulus
      relations (associative symmetry) were tested. The subject showed a significant
      emergence of symmetry only when the spatial arrangements of stimuli were changed
      between the baseline and test trials. In Experiment 2, the subject was tested
      under the condition where the action to constructed paired-object was common to
      all stimuli. The subject showed significant above-chance performance in the
      transitivity test, but not in the symmetry tests. The present results are
      generally consistent with previous studies in chimpanzees that show weak evidence
      for the emergence of symmetry.

PMID- 12199056
TI  - [Boundary extension as the effects of scene context on picture-memory].
AB  - Boundary extension is a picture-memory phenomenon that viewers remember seeing
      wider-angle view than was actually depicted in a photography. To explain boundary
      extension, Intraub, Bender and Mangels (1992) proposed the scene context
      hypothesis that boundary extension is due to viewer's expectancy of scene
      continuity outside the camera's field of view. The present study tested this
      hypothesis. Experiment 1 replicated the phenomenon of boundary extension. In
      Experiment 2, a retention interval did not have much effects on this distortion.
      Experiment 3 revealed that the occurrence of boundary extension was affected by
      activation of scenic representation that would have existed outside the picture
      frame. These results supported the scene context hypothesis.

PMID- 12199058
TI  - [Relationship between anxiety and physical traits of facial expressions].
AB  - The purpose of this study is to investigate correlations between anxiety and
      physical traits of facial expressions. In this study, subjects were divided into
      two groups on the basis of MAS (manifest anxiety scale), and were taken pictures
      under three different conditions. In Analysis I, we examined how facial
      expressions differ between high-anxiety and low-anxiety groups. The results
      showed that facial expressions differed between two groups especially in mouth,
      left half of the face, and asymmetry of the face. In Experiment I and II, we
      investigated whether human beings could identify one's anxiety trait and apparent
      anxiety in facial expressions only on the basis of its facial expressions. The
      results showed that one's anxiety trait and apparent anxiety could be detected
      through the mouth. From these results, human beings can recognize one's anxiety
      through its facial expressions.

PMID- 12199057
TI  - [Effects of the speech rate on speakers' personality-trait impressions].
AB  - This study found non-linear functional relations between speech-rate and
      impressions of speakers' personality-traits. University students (N = 376)
      evaluated speakers' personality impressions for speech sounds that were converted
      at different speech-rates from the original utterance spoken by four Japanese and
      four native English speakers. A short version of the Big Five Scale based on the
      five-factor model of personality was used. Factor analysis showed that listeners
      recognized each personality-trait independently through speech sounds, and that
      speech-rate affected personality impressions of speakers differently depending on
      the traits. Multiple regression analysis revealed that quadratic regression
      equations could provide good approximations of personality-trait values, and all
      the non-linear relationships were described fairly well. The locations of the
      peaks and the spread of the quadratic functions vary from trait to trait. The
      complex metamorphosis of personality impressions via speech-rate converted sounds
      can be inferred by combining those five curves. Finally, participants showed more
      sensitive responses to Japanese speakers than to English speakers.

PMID- 12199059
TI  - [Structure of guilt eliciting situations in Japanese adolescents].
AB  - The aim of the present study was to specify guilt eliciting situations for
      Japanese adolescents, and examine the relationship between guilt-proneness in the
      situations and personality traits. With an open-ended questionnaire, 315 guilt
      experiences were collected and categorized into 37 situations. Situational Guilt
      Inventory (SGI) for the 37 was developed and administered to 500 Japanese
      adolescents. Factor analysis found four factors: hurting others, inconsiderate to
      others, acting selfishly, and debt feeling toward others. SGI scores had positive
      correlations with private and public self-consciousness and depression. However,
      correlations with the Big Five were low, none higher than .2, except those with
      conscientiousness. The factors were similar to those of Dimension of Conscience
      Questionnaire (DCQ; Gore & Harvey, 1995) and Situational Guilt Scale (SGS; Klass,
      1987), except that they do not have the fourth: debt feeling. These results
      showed some characteristics of guilt among Japanese people, as well as
      reliability of the inventory.

PMID- 12199060
TI  - [On the nature and origin of 'nigate'].
AB  - This study examined the nature and origin of 'sense of nigate,' which is an
      awkward and uncomfortable feeling one has toward specific, relatively few others,
      especially in a interpersonal situation. Study 1 investigated its nature with a
      questionnaire administered to company employees (200 men and 45 women) and
      undergraduates (243 men and 205 women). Two factors were found for the sense:
      troublesomeness and apprehension. It should be noted that apprehension was lower
      for management than non-management workers. This tendency was due to the worker
      position, rather than his/her age. In Study 2, self-monitoring scale (Lennox &
      Wolfe, 1984) was administered to 60 high school students (12 men, 47 women, and
      one unknown), to investigate the origin of the sense. As predicted, sense of
      nigate had a negative correlation with the ability to modify self-presentation,
      and positive one with the sensitivity to expressive behavior in others.

PMID- 12199061
TI  - [Comparison of railway employees and college students as evaluator of vibration
      discomfort].
AB  - Typically, vibration discomfort of railway cars was studied with railway
      employees as evaluator, because of their availability and interest, as well as
      various study requirements. However, it has not been shown that employees are
      appropriate for the task. In this study, railway employees were compared with
      college students in order to find how their ratings compared with those by
      ordinary passengers. An experiment was conducted in a running train, and 41
      persons participated; about a half were railway employees and the other college
      students who were invited as non-specialists. Their task was to rate vibration
      discomfort on a scale of 1 to 4, continuously at an interval of 5 seconds.
      Results indicated that employee ratings showed smaller individual differences and
      in general were more cautious than the student ratings.

PMID- 12199062
TI  - [Visual representation for object recognition and visuomotor control: an
      evaluation using two orientation matching tasks].
AB  - This study examined effects of binocular information on visual orientation
      perception and visuomotor control of a hand using two tasks in which observers
      matched the orientation of two rods. On the perceptual matching task, they were
      asked to make a visual judgment of the orientation of two rods. On the motor
      (preshaping) task, they were asked to move a rod which they can not see by their
      hands so as to match the orientation of the presented rod. Decrement in
      availability of binocular cues produced considerable disruptions on the motor
      task, while did less disruptions on the perceptual matching task. Hence binocular
      information seemed to play a critical role on the motor task. These results are
      consistent with recent suggestions that visual perception and visually guided
      motor control should be mediated by separate visual pathways.

PMID- 12199063
TI  - [Possibility of solving complex problems by recursive thinking].
AB  - This study examined the ability in recursive thinking to solve problems. To think
      recursively is one of the most effective ways to break up large and complex
      problems into smaller ones. This study prepared two problems with the same tail
      recursion: The "Guess-the-Number game" and the "Hat puzzle (Wise men puzzle)."
      Because participants (N = 35) were not familiar with recursive thinking, they
      learned how to think recursively in the Guess-the-Number game. Then, we tested
      whether they could solve the Hat puzzle recursively. The results show that two
      thirds of the participants could solve the problem recursively, even if the size
      of the problem increased. Furthermore, their solution times had differed between
      correct and incorrect answers. This suggests that the difference reflected a
      "saving" of effort for problem solving.

PMID- 12199064
TI  - [Effect of increased task procedures on correlation dimensions of the
      electroencephalogram].
AB  - Changes in correlation dimensions of the electroencephalogram (EEG) were examined
      in three different tasks. These three tasks differed from each other with respect
      to the number of procedures. In the present experiment, left-hand movement and
      mental arithmetic were controlled, respectively, during an auditory linguistic
      task. Subjects were 13 healthy right-handed males. EEG signals from eight
      electrode sites were analyzed and the correlation dimensions were obtained. In
      addition, the relative power was obtained for the alpha band. An increase in the
      number of procedures yielded high dimensionality on the occipital EEG. In
      contrast, left-hand movement had no significant effect on EEG dimensions over the
      motor area. The relative power of the alpha band was seen to decrease in all
      channels as the number of procedures increased. The fact that changes in EEG
      dimensions did not necessarily exhibit a simple correspondence to changes in
      alpha wave activity was also discussed.

PMID- 12199065
TI  - [Collage work characteristics and personality].
AB  - The purpose of this study was to investigate the relationship between personality
      and characteristics in collage work. Seventy undergraduates filled the Yatabe
      Guilford (YG) personality test and produced a piece of collage work. The YG
      personality types were not different in terms of collage work characteristics.
      However, emotional adaptation and introvert/extrovert scores were reflected in
      the number of cuttings used in the piece. General activity score was reflected in
      the number of vehicle pictures used. Those who used an eye picture had a tendency
      to be depressed and lacking in confidence. Those who used a "stone circle"
      picture tended to be more emotionally adapted and extroverted. The results
      suggested a possibility that personality traits were reflected in specific
      characteristics in collage work.

PMID- 12199066
TI  - [Basis for indicators of acid-base status of blood and metabolic processes in
      rats under hibernation and under trivial analgesia for foreleg amputation].
AB  - The article deals with some data on investigation of the blood acid-base balance
      main blood indices and metabolic processes in the rats organism under the
      artificial hibernation and trivial anesthesia at the foreleg amputation. This
      model of the artificial hibernation was shown as capable to be promising the hard
      and complicated operative intrusions in the organism.

PMID- 12199067
TI  - [Correction by nicotinamide and nicotinoyl-GABA of dopamine metabolism in rat
      brain in experimental Parkinson's disease].
AB  - It was established, that serotonin and dopamine content and dopamine uptake by
      brain nerve endings under experimental parkinsonism are decreased. Nicotinamide
      nicotinoyl-GABA administration leads to normalization these parameters. It was
      shown that NAm was more effective on serotonin content while nicotinoyl-GABA on
      dopamine one. Dopamine uptake was impaired at experimental parkinsonism and
      partially was normalized by incubation with NAD (10(-6) M). Thus, NAm, nicotinoyl
      GABA and NAD are involved in the regulation of brain neurotransmission under
      experimental parkinsonism and can be useful in treatment of Parkinson's disease.

PMID- 12199069
TI  - [Activity of nitric oxide synthase, poly-(ADP-ribose)-polymerase, protein kinase
      C, protein kinase ASK 1 and internucleosome fragmentation of DNA in HER-2 cells
      during molybdenum-induction of xanthine oxidase].
AB  - It was established that Mo-dependent induction of xanthine oxidase activity
      caused the decrease of NO aerobic oxidation products as well as S-nitrosothiols
      concentrations in the HEP-2 cells. The ASK 1 activity in these cells strongly
      increased and respectively poly-(ADP-ribose)-polymerase as well as protein kinase
      C activities evidently decreased. The internucleosomal DNA fragmentation in the
      Mo treated cells increased.

PMID- 12199068
TI  - [The role of xanthine oxidase in the cytotoxic action of nitrates and nitrites].
AB  - It is established, that in rat organism nitrites and nitrates can be restored in
      nitrogen oxide due to nitrate and nitrite reductase activity of xanthine oxidase
      system. The rat thymocytes were shown in the experiment in vitro to have nitrate
      reductase activity, which was activated by hypoxanthine and inhibited by
      allopurinol. As a result of thymocytes apoptosis, provoked by papaverine, there
      is an essential increase of nitrate reductase activity of xanthine oxidase. The
      comparative research of thymocytes destruction character under the action of
      sodium nitroprusside (NP), N-nitrosodimethylamine (NDMA), NaNO2 and NaNO3 has
      been revealed, that their cytotoxicity, is dose-dependent and it decreases in
      order of these compounds mentioning. Synergism is revealed at the action on
      thymocytes of NP combined with sodium nitrite. These data as the results of
      investigation of EPR-spectrometry as well as use of thymocytes, containing a trap
      -complex of diethyldithiocarbamate-iron (DETK-Fe), allow to assume, that
      cytotoxic effect of NP is caused by the action of liberated from it. Cytotoxic
      action of nitrate is connected with reducibility to nitrite which influences on
      the cells independently, and nitrite action doesn't depend on its transformation
      to NO. The death of thymocytes caused by N-nitrosodimethylamine is not a result
      of its denitrozation.

PMID- 12199070
TI  - [Acid-base homeostasis of the newborn calf].
AB  - Homeostasis of acid-base condition in newborn calves is ensured with metabolic,
      respiration--excretion and buffer systems, which allows for fast adaptation of
      animals to new living condition.

PMID- 12199071
TI  - [Effect of quercetin on some indicators of the proteinase-proteinase inhibitor
      system in rats upon administration of cobalt chloride to them].
AB  - The results of quercetin effect on some changes of proteinase--proteinase
      inhibitor system parameters in rats under cobalt chloride injection are shown. It
      was established that preliminary quercetin administration prevened neutral
      proteinase activation and alpha-2-macroglobulin activity decreasing after 2 h of
      cobalt chloride influence.

PMID- 12199073
TI  - [Erythrocyte membrane fatty acids in ischemic heart disease].
AB  - The erythrocyte ghosts fatty acid composition of 27 patients with coronary artery
      disease (CAD) and 6 healthy people were investigated. Patients suffering from CAD
      were divided in two groups. The first group was matched by 18 patients with CAD
      and essential hypertension (EH) and 9 patients with CAD without EH. Significant
      decrease of the levels of some saturated fatty acids such as palmitic, stearic
      and begenic acids in the erythrocyte ghosts of the patients with CAD without EH
      was established among the major changes of the erythrocyte ghosts fatty acid
      composition. At the same time the amount, of arachidonic acid increased by 74%
      and docosahexaenoic acid--by 5.7 times. The content of miristic, palmitic and
      stearic acids was also diminished in patients with CAD and EH. The percent of
      arachidonic acid was elevated by 51% and docosatrienic acid--by 94%. It is
      notable that the quantity of docosahexaenoic acid did not change markedly if
      copmare to healthy people but was fallen for 5 times if compare to patients with
      CAD without EH. It was suggested that the lack of adaptive changes in erythrocyte
      ghosts omega-3 fatty acids of patients with CAD and EH was an important factor
      which could rise the risk of heart attack development.

PMID- 12199072
TI  - [Activity of cytochrome P-450 aromatase, nitric oxide synthase and level of S
      nitrosothiols in rat ovaries and uterus under oxidative stress caused by cobalt
      chloride].
AB  - Cytochrome P-450 aromatase and nitric oxide syntase activities were established
      to decrease in the ovaries and uteri of CoCl2 injected Wistar female rats.
      Respectively the S-nitrosothiols concentration was also decreased. The quantity
      of malonic dialdehyde was increased in the ovaries and uteri of rats injected by
      CoCl2. It's assumed that reactive oxygen species formed by CoCl2 inhibit the
      activities of aromatase and nitric oxide syntase as haem ligands and inhibitors
      of it's biosynthesis.

PMID- 12199075
TI  - [Anaerobic catabolism of protein in fish].
AB  - It has been accepted that in animals proteins are catabolized by aerobically.
      However, at description of anaerobic metabolism in fish the term "anaerobic
      protein oxidation" is intensively used. This work analyzes the metabolic pathways
      showing that protein metabolism in anaerobic conditions is not real oxidation,
      but it is just redistribution of oxidation levels between parts of molecules of
      amino acids. The process may create preconditions for recovery from anoxia. We
      mean the increase of lipid reserves. If just carbohydrates are metabolized,
      because of reductive equivalents deficiency this way cannot be realized, but at
      simultaneous protein catabolism this system is redox balanced. If amino acids are
      metabolized to lipids and ammonium and carbon dioxide are excreted from the
      organism, general level of organism oxidation is increased, because the most
      oxidized amino acid part is excreted in environment.

PMID- 12199074
TI  - [Phenomenologic mechanokinetic model of Ca2+-dependent contraction-relaxation of
      smooth muscle].
AB  - Phenomenological mechanokinetic model of the smooth muscle contraction response
      that based on the idea of separate contraction and relaxation phases additivity
      realizing in the Ca(2+)-dependent "parallel" dynamic regime was elaborated and
      tested in the biophysical tensometrical experiment. This model application may be
      perspective for the further development of conceptions concerning kinetic and
      energetic regularities of muscle contraction and its quantitative
      characteristics.

PMID- 12199076
TI  - [Endogenous factors in regulating Na+,K+-ATPase in small intestinal mucosa].
AB  - In the combination of gel- and ion exchange chromatography low-molecular weight
      (Mm < 1000 Da) fractions of tissue extracts of small intestine epithelium with
      high activity towards the Na+,K(+)-ATP-ase were obtained. The influence of these
      fractions on the Na+, K(+)-ATP-ase of small intestine epithelium and rat renal
      cortex is studied and discussed.

PMID- 12199077
TI  - [Identification and characterization of "basal" Ca2+-independent Mg2+-dependent
      ATP-hydrolase enzymatic activity in smooth muscle cell plasma membrane
      fractions].
AB  - It is shown, that for correct definition of "basal" Ca(2+)-independent Mg(2+)
      dependent ATPase ac-activity (10-13 mmol Pi/hour on 1 mg of protein) in a
      fraction of uterus smooth muscle cell plasma membranes is necessary to use in
      medium without calcium of an incubation not only EGTA and digitonin--of the
      factor of infringement in activity by this subcellular structure, but inhibitors
      of others Mg(2+)-dependent ATP-hydrolyse enzymatic systems localized as in plasma
      membrane (Na+, K(+)-ATPase) and in others subcellular frames, first of all, in
      mitochondria (Mg(2+)-ATPase) and endoplasmic reticulum (transport Ca2+, Mg(2+)
      ATPase). In the case of a sacolemal fraction of a smooth muscle the contribution
      of others Mg(2+)-dependent ATP-hydrolyse systems in a common enzymatic hydrolysis
      ATP, which unconnected to functioning "basal" Ca(2+)-independent Mg(2+)-dependent
      ATPase, is very appreciable and achieves 35%. The researches, carried out in the
      frameworks of definition of initial velocity of enzymatic reaction, have enabled
      to define its some properties--cationic and anionic specificity, and also
      sensitivity to action of some inhibitors. It has appeared, that the "basal"
      Ca(2+)-independent Mg(2+)-dependent ATP-hydrolyse reaction is nonspecific rather
      both in relation to cations of divalent metals Me2+, and cations of monovalent
      metals and anions, which were utilized for support of ionic strength. The cations
      La--antagonist of cations Ca--practically did not influence enzymatic activity.
      The non-specific inhibitors transport of ATPases--p-chloromercuribenzoate, o
      vanadate and eosine Y with a various degree of efficiency inhibited "basal"
      Ca(2+)-independent Mg(2+)-dependent ATP-hydrolyse reaction. On the basis of the
      analysis of the own and literary data the conclusion is made that "basal" Ca(2+)
      independent Mg(2+)-dependent ATPase of a smooth muscle cell plasma membrane is
      considerably less sensitive to action of nonspecific inhibitors of the Ca(2+)
      transporting systems, than these systems.

PMID- 12199078
TI  - [Interaction of alkaline earth and transition metals with Na+/Ca2+-plasma
      membrane exchanger in secretory cells of the gastric gland].
AB  - Investigation of Na(+)-dependent Ca2+ uptake into the secretory cells of isolated
      gastric glands from guinea pig with the use of calcium isotope (45Ca2+) has been
      performed. The presence of Na+/Ca(2+)-exchanger in the cells membrane was
      established. Ca2+ uptake into the cells through Na+/Ca(2+)-exchanger was
      competitively inhibited by the number of alkaline earthy and transient metals"
      cations. Potency of inhibition increases in such an order (Ki, mM): Ba2+ (117.7)
      < Sr2+ (53.4) < < Mn2+ (15.2) < < Co2+ (12.8) < Cd2+ (8.6). By one-factor
      dispersion analysis it was shown that potency of inhibition depends on ionic
      radii and hydration enthalpy of metals" cations (hx2 = 93.93-94.15%) and also on
      stability constants of their complexes with oxygen-containing bioligands (acetic,
      aspartic and glutamic acid) (hx2 = 82.32-82.47%). Dependence of inhibitory
      constants from ionic radii is most adequately described by the parabolic
      equation, such dependence from hydration enthalpy and stability constants with
      oxygen-containing bioligands--by exponential or multiplicative equations. The
      conclusion has been made that velocity of Ca2+ transport through Na+/Ca(2+)
      exchanger and potency of its inhibition by metals" cations is determined by the
      interaction between energy of their interaction with cation-binding sites of
      transport system and energy of hydration. Energetics of such interactions mainly
      depends on the steric conformity between the metal cation and cation-binding
      sites of the exchanger.

PMID- 12199079
TI  - [Photopolymers as an immobilized matrix in biosensing].
AB  - Biosensors are perspective devices for analysis of substances in chemistry,
      biological chemistry, medicine, biotechnology and also for environment status
      monitoring. Their advantages are compact size, short time of analysis, display
      high response and simplicity in usage. The working characteristics of biosensors
      often depend on efficacy of a biological stuff immobilization on the surface of
      transducer. In this context there is a need for development of immobilization
      methods capable to provide for execution of the following demands: 1)
      compatibility of this process with technology of building transducer; 2)
      simplicity in fulfillment, cheapness and expressness at manufacture of
      biomembranes; 3) ability to provide the maximal safety of a biological stuff
      activity and its high adhesion to a surface of transducer; 4) reproducibility at
      serial application and capacity of standardizing. Usage of photocrosslinked and
      photopolymerized compound at the immobilization of a biological stuff allows to
      provide execution of the listed above demands. The present review is devoted to
      features of application of the given class of compound at building of biosensors.

PMID- 12199080
TI  - [Effect of tocopherol and tocopherol quinone complexes with proteins on activity
      of leukotriene B4 lipoxygenase].
AB  - While estimating the effect of tocopherol, tocopherylquinone and their complexes
      with the tocopherol-binding proteins from the rat liver cytosole on arachidonate
      5-lipoxygenase from peritoneal-lymphocytes and soybean linoleate-5-lipoxygenase
      alpha-tocopherol and especially its complex with tocopherol-binding protein was
      defined to inhibit the activity of both vegetative- and animal nature
      lipoxygenase.

PMID- 12199081
TI  - [Effect of growth regulators on peroxidation processes in corn seedlings under
      salt stress].
AB  - The intensification of lipid free radical oxidation processes and active oxygen
      spicies accumulation in roots and leaves of corn seedlings has been studied by
      chemiluminescence method. 10-days exposition on 0.1 M NaCl decreased their growth
      and influenced on peroxidation intensivity. The maximum of H2O2-initiated
      chemiluminescence in roots was noted at 9th hour whereas in leaves it was
      demonstrated at 48th hour of salt exposition. The effect of seeds treatment by
      synthetic growth regulators methiur and ivin on seedlings growth and peroxidation
      processes in seedlings has been studied. Under salt stress condition both
      substances intensified seedling growth and decreased initiated chemiluminescence
      level. Antioxidative effect of methiur has been more pronounced in roots whereas
      ivin one in leaves. Practical using of these growth regulators for salt-tolerance
      increasing of plants has been suggested.

PMID- 12199082
TI  - Recognition modes of hypoxanthine, xanthine and their derivatives by amino acid
      carboxylic group: UV spectroscopic and quantum chemical data.
AB  - UV absorption spectra of Hyp, Xan, their nucleosides and methyl derivatives were
      studied in anhydrous dimethylsuloxide and the changes in these spectra on the
      interactions with neutral and deprotonated carboxylic groups of amino acids were
      traced. By the semiempirical quantum-chemical method MNDO/H it was shown, that
      interaction with carboxylate-ion fixes Hyp as the rare N7H enolic tautomer and
      converts Xan into its N9H diketo tautomeric form with a probable admixture of the
      N7H O6-enolic form. Significant changes in the UV spectra of Xan, m3Xan, m9Xan
      and X under interaction with carboxylate-ion are determined by essential
      contribution to complex formation of proton transfer from bases to ligands, m9Xan
      and X proving to be slightly protonated even by the solvent. The methylation of
      the N7 position in m7I and m7X was established to result in the practical absence
      of their interactions with carboxylate-ion and initiation of a new ability of
      forming complex with the neutral carboxylic group. Substitution of the C8H group
      by N in 8-azaXan does not change the interaction specificity of the base with two
      forms of carboxylic group.

PMID- 12199083
TI  - [Specificity of antibodies to diphtheria toxin subunits in children with various
      forms of diphtheria infections].
AB  - In order to study the specificity of serum antibodies to separate subunits of
      diphtheria toxin, SDS-electrophoresis of diphtheria toxin preliminary
      disintegrated on the subunits via trypsin treatment was performed, followed by
      immunoblotting assay. 86 blood serum samples of children with diphtheria carriers
      of toxigenic and non-toxigenic strains of Corynebacterium diphtheriae as well as
      children with other infectious diseases similar to diphtheria in their clinical
      manifestation, and healthy ones immunized with DTP-vaccine were tested. A special
      computer program was written and applied for results processing and assumption.
      The data obtained showed that there were particular differences in frequency of
      predominating the antibodies to one or another subunit of diphtheria toxin among
      various groups of the children. We consider that the different specificity of
      antibodies of sick children and children-carriers is capable to predetermine the
      different course of infectious process.

PMID- 12199084
TI  - [Use of cooperative monoclonal antibodies in immunoenzyme analysis for
      determining human tumor necrosis factor].
AB  - A cooperative sandwich enzyme immunoassay (EIA) based on the newly produced pair
      of cooperative monoclonal antibodies (mAbs) against human tumor necrosis factor
      (TNF) was developed and characterized. It was found that, when used
      simultaneously, cooperative mAbs was capable to bind TNF from its preformed
      complexes with soluble TNF receptors (sTNF-R), thus providing the effective TNF
      detection in ex vivo samples by the respective one-step cooperative EIA. While
      demonstrating typical analytical characteristics regarding variability, dynamic
      range and specificity, a cooperative EIA offers an advantageous combination of
      high sensitivity (< 2 pg/ml) and short-time TNF capture protocol (1 hour).
      Application of cooperative EIA for TNF detection in clinical samples has
      demonstrated an increased serum TNF levels in patients with the mixed connective
      disease and infectious endocarditis that positively correlated with severity of
      systemic inflammatory reactions. Production and EIA application of cooperative
      mAbs would be promising in development of standardized and clinically applicable
      immunoassays for cytokines.

PMID- 12199085
TI  - Isolation and immunochemical characterization of immunoglobulin-binding factor
      from bovine peripheral blood lymphocytes.
AB  - The shedding of immunoglobulin-binding factor (IBF) has been studied in
      peripheral blood lymphocytes during 1 h incubation at 37 degrees C. IBF was
      detectable in the incubating medium on the basis of their ability to bind
      immunoglobulin G (IgG) specifically. IBF was affinity purified on Sepharose beads
      coated with bovine IgG, fluoresceinated and identified by their biological
      activities, i.e., for binding immunoglobulin-binding factor labeled with
      fluoresceinizothiocyanate (FITC-IBF) to erythrocytes coated with purified
      antibodies (EAIgG) by fluorometric binding assay. The effect of various pH,
      temperatures and proteolytic enzymes on the binding properties of FITC-IBF to
      EAIgG was also studied. We showed that IBF are sensitive to pronase E, higher
      temperature and pH.

PMID- 12199086
TI  - [Effect of L-arginine and N(omega)-nitro-L-arginine on oxidative phosphorylation
      and lipid peroxidation in rats with various tolerance to hypoxia under stressful
      conditions].
AB  - The influence of L-arginine (600 mg/kg) and NO-synthase blocator N omega-nitro-L
      arginine L-NNA (35 mg/kg) on processes of ADP-stimulated respiration (under using
      0.35 mM succinate, 1 mM alpha-ketoglutarate, 2 mM pyruvate, 2 mM glutamate, 2 Mm
      malate and succinate dehydrohenase blocator--2 mM malonate as substrates of
      oxidation), lipid peroxidation (concentration of DK and MDA), activities of
      succinate dehydrohenase and aminotransferases in rats tissues with different
      resistance to hypoxia under stress conditions have been investigated. It have
      been shown that the energy metabolism indices (respiration rate and efficiency of
      phosphorilation ADP/O) are higher in high resistent (HR) animals in the control
      group. Stress causes the increase of ADP-stimulated respiration in low resistent
      (LR) under succinate oxidation and decrease of NADPH-dependent utilization,
      indicative of more effort of energy system in LR animals. Stress conditions are
      connected with the increase of lipid peroxidation products in blood both in LR
      and in HR animals, though in hepar their concentration change unimportantly.
      Injection of L-arginine decreases aerobic component of energy metabolism on the
      background decreasing aminotransferases ways of oxidation and succinate
      dehydrohenase activity. L-arginine causes decrease of lipid peroxidation products
      in LR, in HR the same effect reaches by L-NNA injection. The has been made
      conclusion about tight correlation between energy metabolism, processes of lipid
      peroxidation with resistance to hypoxia and functioning of nitric oxide cycle
      under stress conditions.

PMID- 12199087
TI  - [Effect of gamma-radiation on contents of lipid peroxidation products in animal
      blood].
AB  - The dynamics of malonic dialdehyde (MD) dependence in the blood serum of Vistar
      line male rats on the intensity of irradiation after a total single irradiation
      with 60Co gamma-quantums in 1.0 and 5.0 Gy doses (during 30 days); 9.0 Gy (during
      15 days) were studied. The MD contents values both in the norm and in 0.5, 1, 2,
      4, 6, 8, 10, 15, 20 and 30 days after irradiation are given. The experimental
      data demonstrated the different sensitivity of the final LPO parameters to the
      doses of 1.0, 5.0, 9.0 Gy radiation depending on the dose power, the changes of
      these parameters being kept for a long time after irradiation.

PMID- 12199088
TI  - [5'-Nucleotidase and adenosine deaminase activity in the rat brain upon prolonged
      effect of low radiation doses].
AB  - The effect of combined low radiation doses (0.2-50.8 cGy) on the 5'-nucleotidase
      and adenosine deaminase activities in the rat hypothalamus, hippocamp and
      cerebral cortex during 45, 120 and 365 days was examined. It has been shown that
      the changes in the 5'-nucleotidase activity of the hypothalamus and hippocamp
      have a phase character. The direction of the changes in enzyme activity of the
      hypothalamus and hippocamp adenosine forming was dependent on the zone stay
      period and had the exactly opposite character depending on the early and
      prolonged stay period in the zone. 5'-nucleotidase activity was changed under the
      influence of mean and lesser doses with an increase of the zone stay period. No
      changes in the 5'-nucleotidase activity of the cerebral cortex were noted. No
      changes in the hypothalamic adenosine deaminase activity of rats that stayed in a
      zone during 45 days were revealed; under the effect of mean dose during 120 days
      the activity decreased and also in case of a higher dosage during one year. The
      adenosine deaminase activity in animal hippocamp decreased in rats only under the
      influence of the lesser dose, for 45-day period. The decrease in adenosine
      deaminase activity of the cerebral cortex that was noted under the effect of all
      the three doses during 45 days, the higher and mean doses during 120 days
      disappeared in a year.

PMID- 12199089
TI  - Dynamics of the changes in homogenate respiratory activity after rat whole liver
      storage at 4 degrees C.
AB  - Homogenate respiratory activity was studied after different storage terms of the
      whole rat liver at 4 degrees C in sucrose-based solution and following
      normothermic reperfusion. Preservation of homogenate respiratory activity in all
      metabolic states after normothermic reperfusion of the control liver (60 min, 4
      degrees C) is shown. Further storage (6 and 24 hrs) of isolated liver under the
      mentioned above conditions strengthens the substrate respiration of homogenate
      both after storage and after normothermic reperfusion. At the same time oxidative
      phosphorylation does not practically change. No change was noted in respiratory
      activity in the states 3, 4ADP and 3DNP after 24 hrs of liver storage in respect
      of a previous term. Following normothermic liver reperfusion contributes to a
      statistically true reduction of mentioned parameters of respiration, that
      correlates with a decrease in the degree of respiration and phosphorylation
      coupled of the studied system.

PMID- 12199090
TI  - Comparative study of the topographic localization of NADPH diaphorase positive
      cells in the rabbit and pheasant thymuses.
AB  - Nicotinamide adenine dinucleotide hydrogen phosphatediaphorase (NADPHd)
      histochemistry was used as a marker for nitric oxide synthase (NOS). In the
      rabbit thymus, NADPHd staining was observed between the capsule and
      corticomedullary junction in radially oriented blood vessels in the cortex. The
      outer surface of the thymic lobule and interlobular septa showed adipocytes
      clumped together. There was a high density of NADPHd positive cells in the
      medulla, without a sharp boundary in corticomedullary space. In addition to
      radially oriented blood vessels in the cortex, they were also found as solitary
      profiles with well stained walls in the medulla. Neuronal plexuses were localized
      in perivascular topography. In the pheasant thymus, NADPHd positive cells were
      present as clusters which were distributed in the medulla and the corticomedullar
      area. NADPHd positive nerve fibres were localized in perivascular topography.

PMID- 12199091
TI  - The effect of CoCl2 on xanthine oxidase, nitric oxide synthase, and protein
      kinase C activity as well as cytochrome P450 1A1, 1A2 and 1B1 quantities in rat
      liver.
AB  - Established that CoCl2 induced oxidative stress activates xanthine oxidase,
      inhibit nitric oxide synthase and cytochrome P450 in the rat liver in vivo. The
      concentration of S-nitrosothiols was respectively decreased and PKC was
      activated. The quantities of general cytochrome P450 as well as its 1A1, 1A2 and
      1B1 isoforms were decreased.

PMID- 12199093
TI  - [Lipoxygenase inhibitors induce rat hepatocyte apoptosis in primary culture].
AB  - Arachidonic acid metabolites have been shown to have a wide range of effects on
      cell proliferation and viability. In this study, the effects of lipoxygenase (LO)
      inhibitors nordihydroguaiaretic acid (NDGA) and caffeic acid (CA) on the
      viability of cultured rat hepatocytes (HC) were investigated. As a result,
      treatment with NDGA and CA for 4 h and 24 h decreased ALT release from HC and
      increased a number of apoptotic cells. Apoptosis inducing effects of general LO
      inhibitor NDGA were more pronounced, than those of 5-LO inhibitor CA. The results
      suggest that lipoxygenase pathway of arachidonic acid metabolism, in particular 5
      LO, is essential regulator of hepatocyte survival and apoptosis.

PMID- 12199092
TI  - [Antioxidant and anti-inflammatory effect of "vitalong" in hyperlipidemia in
      rats].
AB  - In experiment on model of the lipidemia in rats the efficiency of new antioxidant
      drug "Vitalong" was studied. The researches have shown that the drug brakes
      derivation of free radicals, increases activity of a superoxide scavenger, has
      antiinflammatory and adaptogenic operation. Vitalong prevents activation of
      serumal elastasa, locking thus destructive link of the atherogenesis. Ukrainian
      Ministry of Health permits the drug as a preventive means.

PMID- 12199094
TI  - Microanalysis of proteins and peptides.

PMID- 12199095
TI  - [Effect of ethanol on intracellular Ca2+ metabolism].
AB  - The aim of this review is to summarize current thinking on ethanol effects on the
      Ca2+ homeostasis in the excitable tissue cells. It has been shown that acute
      exposure to ethanol decreases cytoplasmic Ca2+ concentration due to Ca2+ channels
      inhibition and Ca2+ pumps activation. Whereas chronic exposure to ethanol
      increases the intracellular Ca2+ concentration in cells due to activation of
      passive Ca2+ transport systems and inhibition of energy-dependent Ca2+ transport
      systems. The emphasis is place on a possible role of pharmacologic agents that
      preserve Ca2+ homeostasis in protecting against ethanol-induced diseases.

PMID- 12199096
TI  - [Plant sulfolipids].
AB  - Plant sulpholipid, sulphoquinovosyl diacylglycerol (SQDG), represents about 12%
      of the lipid mass in higher plants and as the lipid with net negative charge is
      capable to play a specific role in the structural organisation of the membrane.
      SQDG appears to be concentrated mainly in the plant chloroplasts, as in envelope
      so and in lamellar membranes; higher plant chloroplasts are considered to be
      completely autonomous for SQDG synthesis both the DAG moiety and the head group.
      The possible pathway of SQDG biosyntheses and functions are discussed.

PMID- 12199097
TI  - [Calcium-dependent association of membrane rafts].
AB  - The plasma membrane of eucariotic cells is composed from spatially distinct
      regions enriched in sphingomyelin and cholesterol (so called membrane rafts),
      which are surrounded by glycerophospholipid milieu. The ability of these regions
      (membrane microdomains) to recruit specific enzymes and structural proteins
      results in spatial segregation of elements of different signaling systems. To the
      great extent, such segregation is a result of membrane raft association. Our
      results demonstrate that association of individual rafts is a controlled process,
      which is regulated, as many other biological processes, by Ca2+. Annexin II, a
      member of phospholipid-binding protein family, interacts with preparations of
      membrane rafts in a Ca(2+)-dependent manner thus resulting in reversible raft
      association. Occurring in the presence of physiologically relevant calcium
      concentrations these interactions may play a role in regulation of smooth muscle
      contraction.

PMID- 12199098
TI  - [Cationic specificity of a Ca2+-accumulating system in smooth muscle cell
      mitochondria].
AB  - In the experiments conducted with application of an isotopic technique (45Ca2+)
      on the myometrium cells suspension treated by digitonin solution (0.1 mg/ml) some
      properties of Ca ions accumulation system in the mitochondria--cationic and
      substrate specificity as well as effects of Mg2+ and some other bivalent metals
      ions on the Ca2+ accumulation velocity have been estimated. Ca ions accumulation
      from the incubation medium containing 3 mM sodium succinate Na, 2 mM Pi (as
      potassium K(+)-phosphate buffer, pH 7.4 at 37 degrees C), 0.01 mM (40CaCl2 +
      45CaCl2) and 100 nM thapsigargin--selective inhibiting agent of endoplasmatic
      reticulum calcium pump were demonstrated as detected just only in presence of Mg,
      while not Ni, Co or Cu ions. The increase of Mg2+ concentration from 1 x 10(-6)
      to 10(-3) M induced the ATP dependent transport activation in the myometrium
      mitochondria. Under [Mg2+] increase till 40 mM this cation essentially decreased
      Ca2+ accumulation (by 65% from the maximal value). The optimum for Ca2+ transport
      in the myometrium cells suspension is Mg2+ 10 mM concentration. Ka activation
      apparent constant along Mg2+ value (in presence 3 mM ATP and 3 mM sodium
      succinate) is 4.27 mM. The above listed bivalent metals decreased Mg2+, ATP
      dependent accumulation of calcium, values of inhibition apparent constants for
      ions Co2+, Ni2+ and Cu2+ were--2.9 x 10(-4) M, 5.1 x 10(-5) M and 4.2 x 10(-6) M
      respectively. For Mg2+, ATP-dependent Ca2+ transport in the uterus myocytes
      mitocondria a high substrate specificity is a characteristic phenomenon in
      elation to ATP: GTP, CTP and UTP practically fail to provide for Ca accumulation
      process.

PMID- 12199099
TI  - [Generation of proton motive force (Delta mu H+) in Neisseria gonorrhoeae cells].
AB  - The value of the proton motive force in the gonococci cells under incubation
      medium pH changing from 5 to 8 was equal to 183-192 mB. The membrane potential
      changed in the limits from 103 to 145 mB, while the hydrogen ions concentration
      gradient (delta pH) from 47 to 90 mB. The character of phenyldicarbaundecaborane
      absorption by the N. gonorrhoeae vesicules displays the presence of two membrane
      potential generators presence: respiratory chain and H(+)-ATPase. It is shown,
      that the inhibitors of the energy processes KCN, DCCD, CCF cause the suppression
      of proton motive force generators and membrane potential dissipation It is
      marked, that in the gonococci strains resistant to antibiotics the membrane
      potential is higher, than at the sensitive ones.

PMID- 12199100
TI  - [Role of iodothyronine-deiodinase in thyroid hormone mechanisms in animal and
      human cells].
AB  - New data concerning molecular structure, localization and functions of
      iodothyronine deiodinases in animal and human organisms are reviewed in the
      article. Mechanisms of 5- and 5'-deiodination of thyroid hormones by
      intracellular iodothyronine deiodinases are considered, the role of these enzymes
      in the processes of biologically active iodothyronine formation and thyroid
      hormone inactivation are shown. The data which suggest functioning iodothyronine
      5'-deiodinases in the cells of haemopoietic and lymphopoietic systems, and
      connection between the rate of enzyme expression and cell differentiation level
      are adduced. Participation of thyroid hormones and other factors in the
      regulation of expression and functional activities of iodothyronine-5'
      deiodinases in the cells is discussed. The important role of iodothyronine
      deiodinases in mechanisms of optimization of intracellular thyroid status in
      altered physiological state of organism, during ontogenesis and in pathological
      conditions is considered.

PMID- 12199101
TI  - [Regulation of fibroblast adhesion by polyreactive antibodies].
AB  - The effect of polyreactive antibodies on fibroblast adhesion was studied. Dose
      dependent decrease of adhesion was found at the stage of adhesive complex
      formation. A possible mechanism of this effect was determined as a steric
      influence on integrin agregation and clastering.

PMID- 12199102
TI  - [Effect of HIV antigen glycoproteins and morphine on accompanying reactions of
      liberating Ag+-sensitive SH-containing nonprotein compounds in the "antigen
      antibody" interaction].
AB  - The interaction of blood serum immunoglobulins of M, G, and A classes of the
      donors with monospecific serums (MSS)-anti-IgM, anti-IgG and anti-IgG was
      established to be associated by Ag(+)-sensitive-SH containing non protein
      compounds release. This phenomenon formation should be related to a parallel
      running associated reaction mediated by conformational and/or some other changes
      of immunoglobulins macrostructure under highly specific intermolecular
      interaction with adequate MSS in the reactive mixtures. As a rule these processes
      are associated by the break and reduction of mixed disulphide bounds between
      thiol containing nonprotein compounds and proteins. HIV antigen glycoproteins and
      morphine preliminary introduced into the analogic reactive mixtures were found to
      block this phenomenon. If in these reactive mixtures the serums including three
      serotypes hepatitis B virus antigen is introduced this phenomenon is preserved.
      This effect of HIV antigen glycoproteins and morphine could be explained by their
      direct and/or mediated influence on the immunoglobulins macrostructure. As a
      result of the latter the immunoglobulins structure-functional status is
      infringed, being indirectly evidenced by absence of the associated reaction of
      release Ag(+)-sensitive-SH containing non protein compounds in the reactive
      mixtures. The processes presented are capable to play an essential role in
      formation of polyclonal gammapathy under HIV-infection.

PMID- 12199103
TI  - [Activity and properties of phosphofructokinase from while muscle of the horse
      mackerel Trachurus mediterraneus during simulation due to swimming].
AB  - The activity and properties of phosphofructokinase (PFK) in tissues of horse
      mackerel which was swimming at burst regimen for 5 min and at cruiser one for 60
      min have been investigated. In white muscle the PFK activity increased 1.6-fold
      after burst swimming and Hill's coefficient rose as well and decreased 3-fold
      after cruiser one. Swimming did not change the half-maximal saturation constant
      for both substrates and inhibition constants for ATP and citrate. In the
      preparations from white muscle of fish which were stimulated by burst swimming
      the PFK activity at physiological pH values (6.0-7.0) was higher comparing with
      one from the control group and after cruiser swimming. Incubation of preparations
      at 45 degrees C decreased the activity of PFK in control and cruiser swimming
      groups (to 61-67% of initial level) and increased it after burst swimming (1.3
      fold). The mechanisms involving in stable modification of PFK under different
      swimming regimens are discussed.

PMID- 12199104
TI  - [Effect of ethanol on ATP-hydrolase activity of myometrial actomyosin].
AB  - In order of estimating some regularities of ethanol effective action on the
      uterus smooth muscles contractile proteins the effects of spiritus introduced
      into incubation medium on myometrium actomyosine ATP-hydrolase activity and
      superprecipitation was studied. ATP-hydrolase activity was displayed as more
      sensitive to ethanol action; its dependence on ethyl spiritus concentration had
      three-phase character expressed in two inhibiting and one activating sites. While
      defining the kinetic parameters of ATP hydrolysis reaction catalysed by uterus
      myometrium the correlation between inhibition the ATP-hydrolase activity of
      myometrium contractile complex under introducing into incubation medium 2%
      ethanol and decreasing the affinity of actomyosine to Mg2+ was made; the highest
      activating effect of ethanol on ATP-hydrolase activity of actomyosine complex in
      the presence of 8% ethanol correlated with increasing the affinity of actomyosine
      to Mg2+ and ATP.

PMID- 12199105
TI  - [Intermittent hypoxic training and L-arginine as corrective agents for myocardial
      energy supply under acute hypoxia].
AB  - It NO has been shown play to the primary role in several mitochondrial functions.
      Our aim for this study was to investigate whether exogenous NO (L-arginine) or NO
      blocker L-NNA modulated the adaptive reactions of rat myocardial tissue
      respiration on intermittent hypoxic training (IHT). In the control rats an acute
      hypoxic test (inhalation of 7% O2, 30 min) provoked sharp augmentation of ADP
      stimulated tissue respiration with the increase of respiratory coefficient and
      phosphorylation rate, the decrease of O2 uptake efficacy and switching the energy
      supply to succinate oxidation pathway. The same hypoxic test but following 14
      days of IHT (11% O2, 15-min sessions with 15 min rest intervals, 5 times daily)
      produced a stimulation of oxidative phosphorylation with primary activation of
      NAD-dependent pathway, the marked increase of ADP/O ratio. The combination of IHT
      with L-arginine treatment (600 mg/kg intraperitoneally, daily before IHT
      sessions) provoked the decrease of tissue oxygen consumption in comparison with
      untrained animals. L-arginine effects abolished by the NO-synthase blocker L-NNA.
      Its effects on mitochondrial function deals with succinic acid inhibition
      utilizatin (increasing level ADP/O) and activation NADH-dependent oxidation. We
      conclude that the combination of IHT with NO-precursor treatment was capable to
      increase significantly the tolerance to episodes of acute hypoxia.

PMID- 12199107
TI  - [Relative reactivity of thiamine monophosphate and thiamine diphosphate upon
      interaction with alkaline phosphatase].
AB  - Reactivity of thiamin monophosphate (TMP) as calf intestinal alkaline phosphatase
      substrate in model transformations is lower comparing with thiamin diphosphate
      (TDP) reactivity. Under these conditions alkaline phosphatase catalyzes TDP, ADP
      and AMP hydrolysis approximately at same rate. It was shown that TDP competes
      with p-nitrophenyl phosphate more effectively than TMP for the binding in the
      active site. At pH 8.5 and 30 degrees C Km values are as follows: (5.2 +/- 1.6) x
      10(-3) M for TMP and (3.0 +/- 0.8) x 10(-4) M for TDP. Under the same conditions
      the Vmax/Km value for TDP hydrolysis is 53 times higher than the one for
      corresponding reaction of TMP. It was suggested that positively charged
      thiazolium ion of TMP interacts with the nearest environment at the active center
      and by this way reduces enzyme activity.

PMID- 12199108
TI  - [Effect of the substances "Ammivit" and "cerloplasmin" on lipid peroxidation
      products level and of antioxidant system indicators under irradiation].
AB  - It has been shown, that the total X-ray irradiation in the dozes of 0.5 and 1 Gy
      influences on the content of lipid peroxidation products and enzymatic activity
      of antioxidant system in rat spleen and thymus cells. The influence of
      preparations "AMMIVIT" and "Ceruloplasmin" on these processes is investigated
      also. So, the animals feeding by the vitamin concentrate "AMMIVIT" have lead to
      increase of MDA level (a final product of lipid peroxidation) and the
      overactivity of some antioxidant enzymes in rat spleen and thymus cells.
      Injection of the preparation "Ceruloplasmin" to experimental animals up 1 hour
      before the irradiation has normalized LPO intensity and activity of AO enzymes.

PMID- 12199106
TI  - Antioxidative effect of ursodeoxycholic acid in the liver of rats with oxidative
      stress caused by gamma-irradiation.
AB  - We studied effects of ursodeoxycholic acid (UDCA) (10 and 100 mg/kg b.w.) on the
      free radical generation, lipid peroxidation and the antioxidant defense system in
      the liver of rats with oxidative stress caused by gamma-irradiation. Both doses
      of UDCA normalized the liver parameters enhanced by gamma-irradiation: the
      content of superoxide anion and carbonyl-containing products of lipid
      peroxidation (alkanals, alkenals, alkadienals and ketones), the superoxide
      dismutase activity and the chemiluminescence enhanced by luminol. Only the
      highest dose of UDCA (100 mg/kg b.w.) decreased the chemiluminescence enhanced by
      lucigenin in liver microsomes and the hydroxyalkenals content in the liver. UDCA
      prevented reduced glutathione depletion caused by gamma-irradiation, whereas
      glutathione-related enzyme activities did not change under the influence of both
      the UDCA doses as well as gamma-irradiation. Thus, the data obtained suggest that
      UDCA is a metabolite having the sufficiently effective antioxidant properties.

PMID- 12199109
TI  - [The role of respiratory quinolone in treatment of respiratory tract infections:
      focusing on gatifloxacin].

PMID- 12199110
TI  - [Phototoxicity studies of pazufloxacin mesilate, a novel parenteral quinolone
      antimicrobial agent--in vitro and in vivo studies].
AB  - Phototoxicity of pazufloxacin mesilate (PZFX mesilate), a novel parenteral
      quinolone antimicrobial agent, were evaluated in vitro and in vivo studies. In
      vitro, phototoxicity for cultured cells of PZFX, which is active principle of
      PZFX mesilate, was studied, and stability for long-wavelength ultraviolet (UVA)
      was examined. In vivo, phototoxicity tests in guinea pigs and rats, and
      photoallergenicity tests in guinea pigs were conducted. In the phototoxicity test
      on cultured cells, CHL/IU cells were irradiated UVA of 300-3000 mJ/cm2 in the
      presence of PZFX, ofloxacin (OFLX), lomefloxacin (LFLX) or sparfloxacin (SPFX) at
      10 micrograms/mL. Phototoxic potencies for cultured cells of the quinolones
      tested were SPFX > LFLX > OFLX > PZFX. In addition, changes in ultraviolet
      absorption spectrum and residual rate of PZFX, OFLX, LFLX and SPFX were examined
      after UVA irradiation of 300-3000 mJ/cm2 to each solution. PZFX was stable for
      UVA compared with OFLX and LFLX. In the phototoxicity test of guinea pigs, each
      quinolone was administered intraperitoneally daily for 7 days, and UVA of about
      11 J/cm2 was irradiated at 30 minutes after the last administration. Dose levels
      of each quinolone were 65 and 130 mg/kg of PZFX mesilate (dose levels converted
      to PZFX: 50 and 100 mg/kg), 50 and 100 mg/kg of nalidixic acid (NA), 100 mg/kg of
      OFLX, enoxacin (ENX), ciprofloxacin (CPFX), LFLX and SPFX. Grade of skin reaction
      (erythema) at 24 hours after UVA irradiation decreased in the order: SPFX > CPFX
      > NA > ENX = OFLX > LFLX > PZFX mesilate. Thus, PZFX mesilate was found to have
      the weakest phototoxicity. In the maximum plasma concentration of quinolones from
      0.5 to 2.5 hours after administration, corresponding to the time of UVA
      irradiation, the concentration of the group administered PZFX mesilate was about
      4.1 times higher than that of CPFX group, and about 1.3 times higher than that of
      SPFX group. The area under the blood concentration-time curve (AUC0.5-2.5) of the
      group administered PZFX mesilate was the same as that of SPFX group, and about
      3.2 times larger than that of CPFX group. These data showed that phototoxicity of
      PZFX mesilate was also weaker than that of CPFX or SPFX in consideration of
      AUC0.5-2.5. In the phototoxicity test of rats injected intravenously, no
      phototoxicity was observed at 130 mg/kg of PZFX mesilate. In the
      photoallergenicity test of guinea pigs, no photoallergenicity was observed by
      PZFX mesilate. As mentioned above, from in vitro studies PZFX was found to be
      stable for UVA irradiation compared with OFLX and LFLX, and phototoxicity for
      cultured cells of PZFX was weaker than that of SPFX, LFLX or OFLX. In addition,
      from in vivo studies phototoxicity of PZFX mesilate was found to be weaker than
      that of NA, OFLX, ENX, CPFX, LFLX or SPFX, and no photoallergenicity was
      observed. Therefore, photosensitive potency of PZFX mesilate might be less than
      that of other quinolones.

PMID- 12199112
TI  - [Evaluation of the Rapid Lumi 'Eiken' using chemiluminescent assay for rapid
      antimicrobial susceptibility testing].
AB  - One hundred ninety eight clinical isolates, including Enterobacteriaceae (70
      strains), Pseudomonas aeruginosa (20 strains), Acinetobacter baumannii (10
      strains), staphylococci (50 strains), enterococci (20 strains), Streptococcus
      pneumoniae (15 strains) and Haemophilus influenzae (13 strains) were tested for
      their antimicrobial susceptibilities by using the Rapid Lumi 'Eiken' (RL). As a
      reference method, broth microdilution method according to the National Committee
      for Clinical Laboratory Standards was used. Then, each MIC obtained by both of
      these methods was compared. In order to improve the discrepancy between MICs
      obtained by both methods, modification of the RL method was studied. All MICs
      using the RL method were obtained with an incubation period of 4 hours. The
      essential agreement (to within one twofold dilution) between MICs obtained by
      both methods was 82%. The false susceptible in the RL method test results (very
      major error) and the false resistant in the RL tests (major error) were 0.9% and
      2.3%, respectively. The agreement of interpretive category (that is, when the
      categories obtained by both methods are in perfect agreement) was 89%. Proteus
      spp. and A. baumannii showed low essential agreements, 59% and 46% respectively.
      The differences were resulted from the RL method's MICs being higher than the
      reference method. In order to improve the difference between both methods, the RL
      method's procedure was modified in the inoculum size (10(6) CFU/mL to 10(5)
      CFU/mL), the menadione concentration (5 mg/L to 25 mg/L) and the interpretive
      criteria for Enterobacteriaceae and A. baumannii. As the results of the
      modification, the essential agreement in Proteus spp. and A. baumannii increased
      to 82% and 81%, respectively, and there was no significant change in the other
      species of Enterobacteriaceae. In the case of the modified RL method to
      Enterobacteriaceae and A. baumannii, the essential agreement, the very major
      error, the major error and the agreement of interpretive category of all 198
      strains were 87%, 1.4%, 1.5% and 90%, respectively. In conclusion, with only 4
      hour incubation period, the RL method based on chemiluminescent assay gave
      reliable susceptibility testing among the most clinically important bacteria.
      Although several tests showed low essential agreement, it was possible to improve
      by use of the modified RL method. The Rapid Lumi 'Eiken' will provide useful
      information for choosing the most effective antibiotic for primary treatment to
      bacterial infections.

PMID- 12199111
TI  - [Drug interactions between nonsteroidal anti-inflammatory drug and pazufloxacin
      mesilate, a new quinolone antibacterial agent for intravenous use: convulsions in
      mice after intravenous or intracerebroventricular administration].
AB  - Convulsant activity of pazufloxacin mesilate (PZFX mesilate), a new quinolone
      antibacterial agent for intravenous use, in combination with nonsteroidal anti
      inflammatory drug (NSAID) was investigated in mice after intravenous or
      intracerebroventricular administration. Following results were obtained. 1. In
      combination with 4-biphenylacetic acid (BPAA) at an oral dose of 100 mg/kg, PZFX
      mesilate did not induce any convulsions at intravenous doses up to 200 mg/kg.
      Reference quinolones induced convulsions at the following intravenous doses:
      Enoxacin (ENX), 3.13 mg/kg or more; norfloxacin (NFLX) and lomefloxacin (LFLX),
      6.25 mg/kg or more; ciprofloxacin (CPFX), 50 mg/kg or more; sparfloxacin (SPFX)
      and temafloxacin (TMFX), 100 mg/kg or more; fleroxacin (FLRX), 200 mg/kg. 2. PZFX
      mesilate at an intravenous dose of 50 mg/kg did not induce convulsions in mice
      after oral administration of any of 14 kinds of NSAIDs. It induced convulsions at
      200 mg/kg in combination with aspirin at an oral dose of 600 mg/kg, while it did
      not with the other 13 kinds of NSAIDs. 3. Convulsion-inducing dose of PZFX
      mesilate after intracerebroventricular administration was 100 mg/body, which was
      higher than those of reference quinolones (NFLX, CPFX, ENX, LFLX, TMFX,
      levofloxacin, ofloxacin, FLRX and SPFX) and beta-lactam antibiotics (penicillin
      G, cefazoline, imipenem/cilastatin and panipenem/betamipron). In addition,
      concurrent dosing of BPAA (1 microgram/body) did not reduce the convulsion
      inducing dose of PZFX mesilate. These results suggest that PZFX mesilate has
      remarkably weak convulsant activity.

PMID- 12199113
TI  - [In vitro resistance acquisition in Mycoplasma gallisepticum against ofloxacin,
      tylosin and spectinomycin].
AB  - To clarify a mechanism of acquired resistance of two Mycoplasma gallisepticum
      (MG) strains against ofloxacin (OFLX) along with tylosin (TS) and spectinomycin
      (SPCM) as the controls, in vitro resistance acquisition test was carried out for
      10 subcultures of each strain with increasing the amount of antimicrobials, and
      maximum growth allowance concentrations (MAC) in 10th and primary subcultures
      were compared. Acquisition of resistance in the strains against OFLX was moderate
      and MAC of the 10th subculture increased twice for one strain and 16 times for
      another one as compared to that of their primary subcultures. Acquisition of
      resistance in the strains against TS was also moderate and MAC of the 10th
      subculture increased 8 times for both strains as compared to that of the primary
      subcultures. Acquisition of resistance against SPCM was quite different between
      the strains. Namely the MAC of one strain increased 512 times, while another one
      did not acquire any resistance.

PMID- 12199114
TI  - [Microbiological and clinical studies of Haemophilus influenzae isolated at
      Kitakyushu Municipal Medical Center from 1996 through 1999].
AB  - Epidemiological and microbiological studies were carried out using 575 strains of
      Haemophilus influenzae isolated from clinical specimens at Kitakyushu municipal
      medical center from January 1996 through December 1999. The strains isolated
      multiply were excluded. The strains of H. influenzae did not increase for 4
      years, and were detected more in summer season, peaked in July, and less in
      winter season. Like the cases of Streptococcus pneumoniae, most (91.8%) of the
      strains was detected in the specimens from the respiratory tract, and also they
      were isolated mainly from infants under 4-years old (25.6%) and adults over 65
      years old (24.2%) MICs of 7 antimicrobial agents, such as ampicillin (ABPC),
      sulbactam/ABPC, cefaclor, imipenem, panipenem, meropenem (MEPM), and levofloxacin
      (LVFX) were determined using broth microdilution methods. Among 575 strains of H.
      influenzae isolated from clinical specimens, 51 ABPC-resistant strains (8.9%)
      produced beta-lactamase, and 67 strains (11.6%) were beta-lactamase negative
      ampicillin resistant H. influenzae. The ABPC-resistant strains existed in 20.5%.
      Both of MEPM and LVFX showed excellent antimicrobial activity against H.
      influenzae including ABPC-resistant strains. Four cases of meningitis were
      reviewed. All of H. influenzae isolated possessed type b capsular antigen. All
      patients recovered by appropriate antimicrobial treatment. But one adult patient
      developed serious sequela.

PMID- 12199115
TI  - [Studies on allosamidin and aflastatin, novel inhibitors of important metabolic
      pathways, from microorganisms].

PMID- 12199116
TI  - [The effects of erythromycin and its derivative on the activation of
      transcription factors in human bronchial epithelial cells].

PMID- 12199117
TI  - [Development of the screening system for the bacterial type III secretion
      apparatus inhibitor].

PMID- 12199118
TI  - [Population pharmacokinetics of antibiotics in neonates].

PMID- 12199119
TI  - The intra- and inter-examiner reliability of quantitative light-induced
      fluorescence (QLF) analyses.
AB  - OBJECTIVE: To assess the reliability of the analysis stage of quantitative light
      induced fluorescence (QLF). The QLF analysis involves subjective input from the
      user and this study examines the influence of this on the reproducibility of the
      QLF data. METHOD: QLF images were taken of 20 human molar teeth that had been
      previously subjected to a demineralizing solution (phosphoric acid 37%) to create
      artificial white spot lesions on their buccal surfaces. Following examination of
      the images, 16 were chosen to represent a range of lesion size and severity.
      Three copies were made of the images and each was allocated a different filename.
      10 examiners in three centres were asked to analyse each of the 16 images on
      three occasions, with at least seven days between each attempt. Simple
      instructions describing the analysis procedure were supplied and examiners were
      asked to adhere to these directions. Examiners were asked to rate each of the 16
      teeth on their first attempt both quantitatively (5 point scale) and
      qualitatively in terms of difficulty of analysis. Data reported were the delta Q
      at 5% threshold for each tooth on each of three attempts. RESULTS: Using ANOVA
      and paired t-tests to detect statistical differences, the three attempts of each
      examiner were used to determine intra-examiner reliability. Only one examiner (a
      novice at the technique) demonstrated differences between all three attempts and
      two demonstrated difference between one attempt. When the mean scores were
      compared to determine the inter-examiner reliability, only one examiner's results
      were statistically different when compared with two others. CONCLUSION: This
      study has demonstrated that the analysis stage of QLF is reliable between
      examiners and within multiple attempts by the same examiner, when analysing in
      vitro lesions. Novices at the technique should be trained before analysing
      experimental data.

PMID- 12199120
TI  - Outreach teaching: is this the future for dental education?
AB  - Increasingly clinical teaching for all health professionals is moving out of
      teaching hospitals and into community settings. A recent workshop reviewed the
      place of outreach teaching in undergraduate dental education. This paper defines
      outreach teaching in terms of its main components; identifies its benefits for
      different stakeholders; sets out what is required to make it work; and looks at
      current trends offering opportunities for expansion.

PMID- 12199121
TI  - Are we older and wiser?

PMID- 12199122
TI  - Gloves and aloe vera.

PMID- 12199123
TI  - Spontaneous regression of bilateral dentigerous cysts.

PMID- 12199124
TI  - Confidential medical history?

PMID- 12199125
TI  - Prescribing anomalies.

PMID- 12199126
TI  - Ethics in aesthetics.

PMID- 12199127
TI  - Crowns and other extra-coronal restorations: porcelain laminate veneers.
AB  - Porcelain veneers are resin-bonded to the underlying tooth and provide a
      conservative method of improving appearance or modifying contour, without
      resorting to a full coverage crown. The porcelain laminate veneer is now a
      frequently prescribed restoration for anterior teeth. The sums spent by the
      Dental Practice Board on this type of treatment increased from quarter of a
      million pounds in 1988/89 to over seven million in 1994/95, representing some
      113,582 treatments. Since that time the number has stabilised at over 100,000
      veneers prescribed each year. The objective of this paper is to give a practical
      guide on providing these restorations.

PMID- 12199128
TI  - A 10-year retrospective audit of consecutively completed orthodontic treatments
      in a general dental practice and a hospital orthodontic department.
AB  - During 1993 and 1994, the author took part in the South West Orthodontic Clinical
      Assistant Training Programme and worked as a part-time Clinical Assistant in the
      Orthodontic Department of the Royal United Hospital, Bath. Following the clinical
      assistantship the author continued to treat patients in the hospital department
      but under a General Dental Services contract number. This paper is a personal
      clinical audit of all the orthodontic cases completed within the GDS by the
      author since 1990, both in general practice in Westbury, Wiltshire and at the
      Royal United Hospital (RUH), Bath. The aim of the audit was to evaluate the
      effectiveness of orthodontic treatment carried out by the author, both in general
      dental practice and in a hospital orthodontic department, and to compare
      treatment outcomes with other published results.

PMID- 12199129
TI  - Sialolithiasis: an unusually large submandibular salivary stone.
AB  - Salivary gland calculi account for the most common disease of the salivary
      glands. The majority of sialoliths occur in the submandibular gland or its duct
      and are a common cause of acute and chronic infections. This case report
      describes a patient presenting with an unusually large submandibular gland
      sialolith, the subsequent patient management, the aetiology, diagnosis and
      various treatment modalities available for management of salivary gland calculi
      depending on their site and size.

PMID- 12199130
TI  - The fate of 1,587 unrestored carious deciduous teeth: a retrospective general
      dental practice based study from northern England.
AB  - OBJECTIVE: To investigate the outcome of non-restoration of carious deciduous
      teeth by means of a retrospective analysis of clinical case notes of children
      regularly attending two general dental practices and receiving preventive care.
      DESIGN: Using a carefully defined protocol the fate of deciduous teeth diagnosed
      as carious into dentine but symptomless and left unrestored was determined from
      the sequential examination of the clinical records of 481 children attending at
      least annually. RESULTS: The age at initial diagnosis of carious teeth ranged
      from 1-12 years with the majority of cavities (1,005) presenting by 6 years of
      age. In all, 1,587 teeth were followed until loss from the mouth. Of these, 190
      (12%) were extracted because of pain and a further 60 (4%) became painful and
      were treated, leaving 1,337 (84%) that remained symptomless until being lost. Of
      the 1,337 symptomless teeth, 178 were extracted under general anaesthesia at the
      same time as painful ones. The final group of 1,159 (74%) teeth were exfoliated
      without causing pain after a mean survival time of 1,332 days. Excluding from the
      analysis the 178 extracted, but symptomless teeth, leaves a total of 1,409 teeth
      of which 18% gave pain and were extracted or treated and the remaining 82%
      exfoliated. The strongest determinant of pain was age on diagnosis, the other
      factors being tooth type and extent of the cavity when first seen. The carious
      teeth most likely to cause symptoms were found to be molars that developed
      cavities with pulpal involvement by the age of 3 years, 34% of which caused pain.
      In contrast, those least likely to cause pain were carious molar teeth presenting
      without pulpal involvement after 8 years, only 6% of which produced symptoms.
      CONCLUSION: In these patients, the majority of unrestored carious deciduous teeth
      remain symptomless until shed. The results provide evidence to aid the treatment
      planning of carious deciduous teeth in children regularly receiving regular
      preventive dental care.

PMID- 12199131
TI  - Visual scanning of faces in autism.
AB  - The visual scanpaths of five high-functioning adult autistic males and five adult
      male controls were recorded using an infrared corneal reflection technique as
      they viewed photographs of human faces. Analyses of the scanpath data revealed
      marked differences in the scanpaths of the two groups. The autistic participants
      viewed nonfeature areas of the faces significantly more often and core feature
      areas of the faces (i.e., eyes, nose, and mouth) significantly less often than
      did control participants. Across both groups of participants, scanpaths generally
      did not differ as a function of the instructions given to the participants (i.e.,
      "Please look at the faces in any manner you wish." vs. "Please identify the
      emotions portrayed in these faces."). Autistic participants showed a deficit in
      emotion recognition, but this effect was driven primarily by deficits in the
      recognition of fear. Collectively, these results indicate disorganized processing
      of face stimuli in autistic individuals and suggest a mechanism that may subserve
      the social information processing deficits that characterize autism spectrum
      disorders.

PMID- 12199132
TI  - Asperger syndrome: tests of right hemisphere functioning and interhemispheric
      communication.
AB  - The primary aim of this investigation was to assess to what extent Rourke's
      (1989, 1995) nonverbal learning disabilities syndrome (NLD) model resembles the
      pattern of assets and deficits seen in people with Asperger syndrome (AS). NLD
      can be characterized by a cluster of deficits primarily affecting nonverbal
      aspects of functioning, in the presence of proficiency in single word reading and
      a superior verbal memory. The neurological underpinnings of this syndrome may be
      dysfunction of white matter affecting right hemisphere functioning and
      interhemispheric communication. To explore this hypothesis, eight participants
      with AS (ages 10 to 41 years) were assessed in the following areas: the
      pragmatics of language and communication, verbal and visual memory, visual
      spatial abilities, and bimanual motor skills. Results confirmed the close
      similarity in the neuropsychologic profiles of NLD and AS.

PMID- 12199133
TI  - The facilitation of social-emotional understanding and social interaction in high
      functioning children with autism: intervention outcomes.
AB  - This study evaluated the effectiveness of a 7-month cognitive behavioral
      intervention for the facilitation of the social-emotional understanding and
      social interaction of 15 high-functioning children (8 to 17 years old) with
      autism. Intervention focused on teaching interpersonal problem solving, affective
      knowledge, and social interaction. Preintervention and postintervention measures
      included observations of social interaction, measures of problem solving and of
      emotion understanding, and teacher-rated social skills. Results demonstrated
      progress in three areas of intervention. Children were more likely to initiate
      positive social interaction with peers after treatment; in particular, they
      improved eye contact and their ability to share experiences with peers and to
      show interest in peers. In problem solving after treatment, children provided
      more relevant solutions and fewer nonsocial solutions to different social
      situations. In emotional knowledge, after treatment, children provided more
      examples of complex emotions, supplied more specific rather then general
      examples, and included an audience more often in the different emotions. Children
      also obtained higher teacher-rated social skills scores in assertion and
      cooperation after treatment. The implications of these findings are discussed in
      terms of the effectiveness of the current model of intervention for high
      functioning children with autism.

PMID- 12199134
TI  - Depression in persons with autism: implications for research and clinical care.
AB  - Although several studies have investigated the occurrence of medical and
      neurological conditions in persons with autism, relatively few reports have
      focused on the phenomenology and treatment of psychiatric disorders in this
      population. There is emerging evidence that depression is probably the most
      common psychiatric disorder that occurs in autistic persons. In this review, we
      examine the factors that influence the presence of depression in this population,
      such as the level of intelligence, age, gender, associated medical conditions,
      and the role of genetic factors and life events. We discuss the various forms of
      treatment available and highlight the need for early detection.

PMID- 12199135
TI  - Parent and professional agreement on cognitive level of children with autism.
AB  - The aim of the study was to compare the extent of agreement between parents and
      professional evaluators regarding the cognitive level of children with autism. We
      sought to determine the degree of parent and standardized test agreement about
      the child's cognitive level for children at different levels of cognitive
      functioning. Information regarding parental view of cognitive levels was
      collected from the questionnaires used during the initial evaluation. These
      levels were compared with age equivalencies obtained by professionals from
      standardized intellectual measures. Significant difference between parental
      perception and professional assessment of the child's cognitive level was found.
      In addition, there was significant correlation between the level of agreement and
      cognitive functioning; agreement increased as the level of cognitive functioning
      increased.

PMID- 12199136
TI  - Sensitivity and specificity of the autism diagnostic inventory-telephone
      screening in Spanish.
AB  - We report on the development in Argentina of a screening questionnaire for autism
      administered over the telephone. The Autism Diagnostic Inventory-Telephone
      Screening in Spanish (ADI-TSS) is based on the Autism Diagnostic Interview
      Revised (ADI-R), keeping its structure but including fewer questions, which were
      rephrased to assess them over the telephone. The ADI-TSS went through different
      versions, with each modification gaining in reliability. The final version of the
      ADI-TSS could be assessed in 20 to 40 minutes and demonstrated a high validity
      (using the ADI-R as the diagnostic gold-standard), high intrarater and interrater
      reliability (as measured with intraclass correlations), and high internal
      consistency (as measured with Cronbach's alpha). The validity of the ADI-TSS
      remained high when used by a health-related professional without formal training
      in the assessment of autistic patients. We believe the ADI-TSS is useful in field
      research studies as a screening instrument for patients with a potential
      diagnosis of autism, although future validation studies should include larger
      samples.

PMID- 12199138
TI  - Brief report: attention differences in Asperger syndrome.

PMID- 12199137
TI  - Lateralization in individuals with high-functioning autism and Asperger's
      disorder: a frontostriatal model.
AB  - Neurobiological and behavioural studies of possible left hemisphere dysfunction
      in autism have generated conflicting results. Left hemisphere dysfunction may
      manifest in autism only in tasks that invoke executive functions. Moreover, left
      hemisphere dysfunction may underpin autism but not Asperger's disorder. We thus
      aimed to systematically investigate reports of anomalous lateralization in
      individuals with high-functioning autism and Asperger's disorder. Two of the
      tasks were sensitive to executive dysfunction: a serial choice reaction-time task
      and a Posner-type paradigm; the remaining tasks instead investigated aspects of
      perceptual lateralisation. Compared with age- and IQ-matched controls, the autism
      group displayed deficiencies in right hemispace (and by implication, left
      hemisphere) performance on both executive function tasks; however, this group
      demonstrated normal lateralization effects on the nonexecutive, visual-perceptual
      tasks. In contrast, the Asperger's disorder group showed similar laterality
      effects to their age- and IQ-matched controls on both executive and nonexecutive
      function tasks. The etiological relevance of this neurobehavioral dissociation
      between high-functioning autism and Asperger's disorder was discussed; in
      particular, it was suggested that the period where dominance shifts from right to
      left hemisphere is important in whatever process might dictate the emergence of
      either autism or Asperger's disorder.

PMID- 12199139
TI  - Brief report: immune factors in autism: a critical review.
AB  - Pervasive developmental disorders represent a group of neurodevelopmental
      disorders that affect children early in their development. Autistic disorder is
      the best described of these disorders, yet even this term covers a broad group of
      clinical presentations. Various immune system abnormalities, including
      autoimmunity and defects in different subsets of immune cells, have been reported
      in children with autistic disorder, suggesting that immune factors may play a
      role in the development of autism. Based on anecdotal observation, vaccination
      was proposed to cause autism in some children, but several controlled studies
      have failed to support this claim. Intravenous immunoglobulin infusions has been
      tested as immunotherapy for autism, although the preliminary results are
      inconclusive and there is a risk of potentially fatal transmission of blood-borne
      pathogens. To examine this issue, intensive well-controlled epidemiological and
      bench studies need to be carried out in defined and carefully controlled study
      subjects to establish the cellular and molecular basis of autism, against which
      the effects of each proposed immune factor can be examined.

PMID- 12199140
TI  - Localization of human SMC1 protein at kinetochores.
AB  - Proper cohesion of sister chromatids is prerequisite for correct segregation of
      chromosomes during cell division. The cohesin multiprotein complex, conserved in
      eukaryotes, is required for sister chromatid cohesion. Human cohesion is composed
      of a stable heterodimer of the structural maintenance of chromosomes (SMC) family
      proteins, hSMC1 and hSMC3, and non-SMC components, hRAD21 and SA1 (or SA2). In
      yeast, cohesion associates with chromosomes from late G1 to metaphase and is
      required for the establishment and maintenance of both chromosome arm and
      centromeric cohesion. However, in human cells, the majority of cohesion
      dissociates from chromosomes before mitosis. Although it was recently shown that
      a small amount of hRAD21 localizes to the centromeres during metaphase, the
      presence of other cohesion components at the centromere has not been demonstrated
      in human cells. Here we report the mitosis-specific localization of hSMC1 to the
      kinetochores. hSMC1 is targeted to the kinetochore region during prophase
      concomitant with kinetochore assembly and remains through anaphase. Importantly,
      hSMC1 is targeted only to the active centromere on dicentric chromosomes. These
      results suggest that hSMC1 is an integral component of the functional kinetochore
      structure during mitosis.

PMID- 12199142
TI  - Identification and partial characterization of a new Ceratitis capitata-specific
      44-bp pericentromeric repeat.
AB  - Tandem satellite DNA repeats are often associated with centromeres. In spite of
      their importance in the organization of the centromere, they do not seem to be
      broadly conserved among species and their role is still unclear. Here we report
      the identification of a new 44-bp tandem pericentromeric repeat from the medfly,
      Ceratitis capitata. The repeat is specific to this insect and is not found in any
      of the other closely related species tested. It localizes in four out of its five
      autosomes and in the X chromosome. It is organized in long arrays, interspersed
      by transposable elements and other less well-defined sequence motifs.

PMID- 12199141
TI  - Cytogenetic characterization of telomeres in the holocentric chromosomes of the
      lepidopteran Mamestra brassicae.
AB  - Telomeres of the Mamestra brassica holocentric chromosomes were studied by
      Southern blotting, in-situ hybridization and Bal31 assay evidencing the presence
      of the telomeric (TTAGG)n repeat. Successively, molecular analysis of telomeres
      showed that TRAS1 transposable elements were present at the subtelomeric regions
      of autosomes but not in the NOR-bearing telomeres of the Z and W sex chromosomes.
      TRAS1 appeared to be transcriptionally active and non-methylated, as evaluated by
      RT-PCR and digestion with MspI and HpaII. Finally, dot-blotting experiments
      showed that the 2.8 +/- 0.5% of the M. brassicae genome consists of TRAS1.

PMID- 12199143
TI  - A centromeric satellite DNA may be involved in heterochromatin compactness in
      gobiid fishes.
AB  - Centromere and telomere composition and organization were studied in various
      gobiid species exhibiting and not exhibiting chromosome polymorphisms involving
      Robertsonian rearrangements. In Gobius cobitis, we isolated an AT-rich
      centromeric DNA satellite, designated pCOB, and found that several sequences
      contain adenine stretches, various CA/TG dinucleotide steps, and a sequence 76%
      homologous to the yeast CDE III centromeric sequence. All of these traits are
      generally considered important for centromeric function, and the hypothesis has
      been advanced that some are involved in the control of DNA curvature and thus in
      the degree of centromeric chromatin compactness. Based on these features, and on
      the fact that they are found only in the species not exhibiting Robertsonian
      biarmed chromosomes, a role for pCOB in preventing centric fusions has been
      hypothesized. Our data also suggest that, as in other species, the formation of
      Robertsonian biarmed chromosomes is accompanied by the loss of telomeric
      sequences.

PMID- 12199144
TI  - Active, but not inactive, human centromeres display topoisomerase II activity in
      vivo.
AB  - Eukaryotic centromeres are composed of centromere DNA and the multiple proteins
      directly or indirectly associated with it. One important DNA-binding protein in
      the centromere is DNA topoisomerase II (topo II). In the genome in general, topo
      II has two functions, one structural and one enzymatic, the latter catalyzing DNA
      strand-passage reactions. It has been demonstrated that topo II accumulates at
      centromeres during the first part of mitosis, and disappears again at anaphase,
      but it has not been clear whether it serves a structural or an enzymatic function
      at the centromere. To investigate this issue, we developed the topo II-induced
      self-primed in situ assay (Topo-SPRINS). In this assay, DNA breaks created by
      topo II are stabilized with the topo II inhibitor VM-26 in vivo, and used as
      'primers' for localized DNA synthesis in vitro. The assay revealed that topo II
      has enzymatic activity at mitotic centromeres and that the activity is relatively
      constant across centromeres. Furthermore, the activity was observed at a
      neocentromere, and, in multicentric chromosomes, the activity was restricted to
      the active centromere. The topo II activity is thus selectively present at
      functioning centromeres, indicating that it plays a role in mitotic centromere
      function.

PMID- 12199145
TI  - Cytogenetic differentiation of two sympatric tree shrew taxa found in the
      southern part of the Isthmus of Kra.
AB  - Sympatric populations of the genus Tupaia encompassing two cytotypes (cyt60, 2n =
      60 and cyt62, 2n = 62) were found in the southern part of the Isthmus of Kra (the
      middle region of the Malay Peninsula, Thailand). C-bands, location of rDNA, and
      location of non-essential telomeric repeats (TRs) were investigated in detail for
      23 animals captured in the area. Such chromosomal traits definitely reveal that
      two distinct cytotypes exist in the sympatric population, though the external
      morphological traits are similar. Hybrid cytotypes were not observed; thus, these
      two cytotypes appear to be genetically isolated sibling species. Chromosomal
      results compared with previous data, geographic distribution and morphological
      data observed with new insight suggest that, in the sympatric population, 'cyt60'
      represents members of Tupaia glis, while 'cyt62' identifies individuals of Tupaia
      belangeri. The cytogenetic information discovered in the present study offers new
      insight to morphological classification and, further, may provide substantial
      diagnostic characteristics for the distinction of tree shrew species.

PMID- 12199146
TI  - Crossing over as assessed by late recombination nodules is related to the pattern
      of synapsis and the distribution of early recombination nodules in maize.
AB  - Recombination nodules (RNs) are multicomponent proteinaceous ellipsoids found in
      association with the synaptonemal complex (SC) during prophase I of meiosis.
      Numerous early RNs (ENs) are observed during zygotene, and they may be involved
      in homologous synapsis and early events in recombination. Fewer late RNs (LNs)
      are observed during pachytene, and they occur at crossover sites. Here we
      describe the pattern of synapsis and the distribution of ENs and LNs in maize.
      Synapsis starts almost exclusively at chromosome ends, although later in zygotene
      there are many interstitial sites of synaptic initiation. ENs do not show
      interference, except possibly at distances < or = 0.2 micron. The frequency of
      ENs is higher on distal compared to medial SC segments, and the highest
      concentration of ENs occurs at synaptic forks. The number of ENs on an SC segment
      does not change during zygotene. These observations are interpreted to indicate
      that ENs are assembled at synaptic forks. Like ENs, LNs are more concentrated
      distally on bivalents but, unlike ENs, LNs show interference. A model is
      presented that relates the pattern of synapsis and ENs to the pattern of late
      nodules and crossing over.

PMID- 12199147
TI  - Arachidonic acid inhibition of muscarinic receptor-mediated nitric oxide
      production occurs at the level of calcium mobilization in Chinese hamster ovary
      cells.
AB  - Strong evidence supports that nitric oxide (NO) alters cell signaling pathways
      involving arachidonic acid (AA). Little is known, however, about the reciprocal
      modulation of nitrergic pathways by AA. The effects of exogenous AA on signal
      transduction of M1 muscarinic acetylcholine receptors were investigated in a
      model system of stably transfected Chinese hamster ovary cells. AA concentration
      dependently inhibited the effects of carbachol in producing NO (IC50 = 191
      microM) but did not alter inositol phosphate production or M1 receptor binding.
      AA inhibited both carbachol-induced transient and sustained increase in
      intracellular calcium concentration ([Ca2+]i; IC50 = 11 and 12 microM,
      respectively). Furthermore, AA-induced increase in [Ca2+]i cross-desensitizes
      with thapsigargin, but AA does not inhibit Ca(2+)-ATPase activity. These data
      support the concept that AA concentration-dependently inhibits receptor-mediated
      NO production at the level of calcium mobilization.

PMID- 12199148
TI  - An interaction between ATP and high K+: mutual impairment of ATP- and high K(+)
      evoked [Ca2+]i increase in NG 108-15 cells.
AB  - The interaction between ATP- and high K(+)-evoked increase in intracellular free
      calcium concentration ([Ca2+]i) was investigated to gain an insight into the
      mechanism of interaction of ATP with voltage-sensitive calcium channels. [Ca2+]i
      was measured in the neuronal model, neuroblastoma x glioma hybrid cells (NG 108
      15), using the fluorescence indicator fura-2. In the presence of 1.8 mM
      extracellular Ca2+, ATP induced a rapid, concentration-dependent increase in
      [Ca2+]i. High K+ (50 mM) evoked a [Ca2+]i rise from 109 +/- 11 nM to 387 +/- 81
      nM (n = 16). The application of either of these two [Ca2+]i-increase provoking
      agents in sequence with the other caused impairment of the latter effect. The
      mutual desensitization of the responses to ATP and high K+ strongly suggests that
      both agents rely at least in part on the same source of Ca2+ for elevation of
      [Ca2+]i in NG 108-15 cells.

PMID- 12199149
TI  - Effect of MPTP on Dopamine metabolism in Ames dwarf mice.
AB  - Hypopituitary dwarf mice exhibit a heightened antioxidative capacity and live
      extensively longer than age-matched controls. Importantly, dwarf mice resist
      peripheral oxidative stress induced by paraquat, and behaviorally, they maintain
      cognitive function and locomotor activity at levels above those observed in old
      wild-type animals. We assessed monoaminergic neurotransmitters in nigrostriatal
      tract and cerebellum after the administration of the dopaminergic neurotoxin,
      MPTP. There was no significant change in mitochondrial monoamine oxidase (MAO)-B
      and total MAO activity in the substantia nigra and nucleus caudatus putamen of
      wild-type and dwarf mice. Coenzymes Q-9 and Q-10 were present in similar
      quantities, as were dopamine, norepinephrine, and serotonin levels in the
      cerebellum and nigrostriatal tract. MPTP set off tremor, hind limb abduction, and
      straub tail behavior and induced significant dopamine depletion in the striatum
      of both dwarf and normal mice. This study shows that the MAO activity and the
      coenzyme content of dwarf mice are similar to those of their wild-type controls
      and hence susceptible to MPTP-induced toxicity.

PMID- 12199151
TI  - Depolarization-induced superoxide radical formation in rat hippocampal slices.
AB  - Glutamate is the major excitatory neurotransmitter in the brain. Activation of
      glutamatergic receptors induces neuronal depolarization, and if this activation
      is excessive, it can lead to cellular damage. Evidence for the participation of
      glutamatergic receptor systems in the production of oxygen free radicals in
      neuronal cells is accumulating. In the present study, we have kept hippocampal
      slices under depolarization conditions induced by including 50 mM K+ in
      artificial cerebrospinal fluid (dACSF) and followed superoxide radical formation.
      Superoxide radical formation was increased in dACSF-incubated hippocampal slices.
      We have also attempted to determine the relative contribution of agonist- and
      voltage-sensitive channels to superoxide radical formation by using their
      selective blockers. Superoxide radical formation was suppressed by MK 801,
      memantine, APV, CNQX, and TTX application to dACSF-incubated hippocampal slices.
      Similar studies on different experimental systems may help to unravel the
      underlying critical events and active mechanisms that may lead to superoxide
      radical generation and subsequent neuronal cell death.

PMID- 12199150
TI  - Caspase inhibition protects nerve terminals from in vitro degradation.
AB  - Caspase activation and apoptotic events may take place in terminal regions far
      removed from the cell body and contribute to synapse loss in neurodegenerative
      diseases. For examination of events in terminals, we have developed a cell-free
      assay using quantitative flow cytometric analysis (fluorescence-activated cell
      sorting) of neuronal particles in a P2 synaptosomal preparation (P-2) from rat
      brain as a model system. Staurosporine-induced loss of neuronal particles was
      blocked by nonselective caspase inhibition (z-VAD-fmk) and by calpain inhibition
      (calpain inhibitor II [ALLM]). Phosphatidylserine exposure was increased in the P
      2 by staurosporine treatment, and this increase was blocked by a peptide
      inhibitor of caspase-3-like activity (Ac-DEVD-CHO). Increased caspase activity in
      the crude synaptosomal fraction was confirmed by direct measurement with a
      fluorometric assay. These results indicate activation of both caspase and calpain
      in the P-2 fraction and suggest a role for these cysteine proteases in the in
      vitro degradation of nerve terminals.

PMID- 12199152
TI  - Phosphorylation state, solubility, and activity of calcium/calmodulin-dependent
      protein kinase II alpha in transient focal ischemia in mouse brain.
AB  - During and after middle cerebral artery occlusion in mice, CaMKII alpha protein
      was irreversibly translocated from the soluble to the Triton X-100-nonsoluble
      fraction. This decrease in solubility had a strong effect on activity: CaMKII
      alpha was almost completely inactivated after being translocated. Results from
      solubilization experiments suggest that different mechanisms underlie the
      conversion of CaMKII alpha protein from a soluble to a detergent nonsoluble form
      in ischemic as opposite to nonischemic tissue. Analysis of the phosphorylation
      state of CaMKII alpha revealed that in the total homogenate and the Triton X-100
      nonsoluble fraction, CaMKII alpha phosphorylated at only one site was the
      dominant phosphorylated form, whereas in the soluble fraction CaMKII
      phosphorylated at two sites was the predominant phosphorylated species.
      Investigation of the mechanisms underlying ischemia-induced changes in the
      solubility of CaMKII alpha could help to elucidate processes triggered by
      transient focal cerebral ischemia that lead to neuronal cell injury.

PMID- 12199153
TI  - Differential age-dependent trophic responses of nodose, sensory, and sympathetic
      neurons to neurotrophins and GDNF: potencies for neurite extension in explant
      culture.
AB  - The age-dependent trophic responses of sympathetic, sensory, and nodose neurons
      to the neurotrophins NGF, BDNF, and NT-3 and to glial cell line-derived
      neurotrophic factor (GDNF) were examined by an explant culture system. Superior
      cervical ganglia (SCG), dorsal root ganglia (DRG), and nodose ganglia (NG) were
      removed from rat embryos (E18), neonatals (< or = 1 day old), young adults (3-6
      months old), and aged adults (> 24 months old). The ganglia were cultured with
      and without each neurotrophic factor; the neurite extension and neurite density
      were then assessed. The SCG from rats of all ages were significantly influenced
      by NGF, NT-3, and GDNF; the effects of NT-3 and GDNF were reduced after
      maturation. The DRG from embryos and neonates were influenced by all neurotrophic
      factors; however, the effects of BDNF and NT-3 disappeared after maturation. The
      GDNF showed little effect on adult DRG and no effect on aged DRG. The effect of
      NGF was preserved over all ages of DRG. The NG from embryonic rats were
      significantly responsive to BDNF and GDNF; their effects decreased in the
      neonatal NG, but a minimum effect remained in the aged NG. These results indicate
      that age-dependent profiles of trophic effects differ extensively among the
      lineages of the peripheral nervous system and also among the individual
      neurotrophic factors.

PMID- 12199154
TI  - Relationship between oxidation of glutathione and reactive nitrogen species
      during the early-reperfusion phase of cerebral ischemia.
AB  - A timed profile of glutathione oxidation and reactive nitrogen species during
      reperfusion after cerebral ischemia in rat was obtained. Dialysate was collected
      every 25 min from a microdialysis probe inserted into the cerebral cortex before
      and after cerebral ischemia. NO2-, NO3-, and reduced and oxidized glutathione
      (GSH, GSSG) were detected by high-performance liquid chromatography. GSH and GSSG
      increased and reached a peak: 3408 +/- 1710% (mean +/- SE) at 25 min of
      reperfusion (P < 0.0001) and 329 +/- 104% at 50 min of reperfusion (P = 0.06),
      respectively. Oxidation ratio decreased from 0.82 +/- 0.04 to 0.42 +/- 0.07 (P <
      0.0001) at 25 min of reperfusion. NO3- levels significantly decreased (68.3 +/-
      9.1%) (P < 0.01) during ischemia and remained lower than the control value during
      reperfusion. NO2- levels did not significantly change. These data suggest that
      GSH releases during early phase of reperfusion and that its rapid oxidation
      contributes to prevent an increase in reactive nitrogen species.

PMID- 12199155
TI  - Acetyl-L-carnitine protects against amyloid-beta neurotoxicity: roles of
      oxidative buffering and ATP levels.
AB  - Acetyl-L-carnitine (ALCAR), normally produced in mitochondria, is a precursor of
      acetyl-CoA in the tricarboxylic (TCA) cycle. Since mitochondrial compromise and
      ATP depletion have been considered to play a role in neuronal degeneration in
      Alzheimer's disease (AD), we examined whether ALCAR attenuated oxidative stress
      and/or ATP depletion after exposure of cells to beta-amyloid (Abeta), a
      neurotoxic peptide that accumulates in AD brain. Differentiated SH-SY-5Y human
      neuroblastoma cells were exposed for 2-24 h to 20 microM Abeta in the presence
      and absence of 50 microM ALCAR. ALCAR attenuated oxidative stress and cell death
      induced by Abeta neurotoxicity. Abeta depleted ATP levels, suggesting Abeta may
      induce neurotoxicity in part by compromising neuronal energy. ALCAR prevented ATP
      depletion; therefore, ALCAR may mediate its protective effect by buffering
      oxidative stress and maintaining ATP levels.

PMID- 12199156
TI  - 3-nitropropionic acid-induced changes in bilayer fluidity in synaptosomal
      membranes: implications for Huntington's disease.
AB  - The use of 3-nitropropionic acid (3-NP) and other mitochondria inhibitors to
      effectuate animal models of Huntington's disease has been well established. 3-NP
      administration has been shown to lead to pathology similar to that of HD,
      including massive loss of striatal neurons associated with oxidative stress.
      Oxidative stress induced by 3-NP also extends to the cortex, an area where little
      neuron loss occurs. No mechanism as of yet accounts for selective loss of
      striatal neurons while sparing cortical neurons. In the present study, a
      nitroxide stearate lipid bilayer-specific spin-label was utilized to probe 3-NP
      induced fluidity changes in striatal and cortical synaptosomal membranes. In
      cortical synaptosomes, membrane fluidity increased in animals previously treated
      with 3-NP when compared to controls injected with saline vehicle, while in
      striatal synaptosomes, membrane fluidity decreased in animals treated with 3-NP
      when compared to controls. The results of the present study suggest that
      oxidatively-induced changes in membrane fluidity may be involved in mechanisms by
      which selective striatal neuronal loss occurs in this animal model of
      Huntington's disease.

PMID- 12199157
TI  - Ontogenetic study of the effects of energetic nutrients on amino acid metabolism
      of rat cerebral cortex.
AB  - We studied the effect of various energetic nutrients on metabolism of L-[U
      14C]leucine and [1-14C]glycine in cerebral cortex of rats at different ages. At
      gestational age, glucose and lactate stimulated protein synthesis from L-[U
      14C]leucine and [1-14C]glycine and from L-[U-14C]leucine, respectively; glucose,
      beta-OH-butyrate and lactate stimulated lipid synthesis from L-[U-14C]leucine. At
      10 days of age, glucose, mannose, and fructose stimulated protein synthesis, and
      glucose and mannose stimulated oxidation to CO2 as well as lipid synthesis from L
      [U-14C]leucine. In adult rats, glucose, mannose, and fructose stimulated protein
      synthesis from L-[U-14C]leucine and [1-14C]glycine; glutamine also markedly
      decreased the oxidation of L-[U-14C]leucine and [1-14C]glycine in 10-day-old and
      adult rats.

PMID- 12199158
TI  - Effects of chronic restraint stress on feeding behavior and on monoamine levels
      in different brain structures in rats.
AB  - Monoaminergic systems are important modulators of the responses to stress. Stress
      may influence feeding behavior, and the involvement of monoamines in the control
      of food intake is well recognized. We investigated the effects induced by chronic
      restraint stress, 1 h a day, for 40 days, on eating behavior and on monoamines in
      distinct brain structures. Increased consumption of sweet pellets, and not of
      peanuts, was observed. Dopamine (DA), serotonin (5-HT), and their metabolites
      were measured by HPLC-EC. After chronic restraint, the results observed were
      decreased 5-HT in hippocampus, with increased 5-HIAA/5-HT; decreased 5-HIAA
      levels in cortex; reduction in DA in hippocampus, and increased levels in
      amygdala and hypothalamus; HVA increased in cortex, as well as HVA/DA ratio,
      while DOPAC/DA decreased. HVA decreased in hypothalamus, as well as HVA/DA, and
      DOPAC/DA and HVA/DA decreased in the amygdala. These results suggest that
      restraint stress differentially affects the activity of central dopaminergic and
      serotonergic neurons, and this may be related to the effects observed in eating
      behavior.

PMID- 12199159
TI  - Changes of the level of G protein alpha-subunit mRNA by tolerance to and
      withdrawal from pentobarbital in rats.
AB  - Pentobarbital was continuously infused intracerebroventricularly (i.c.v.) at the
      rate of 300 micrograms/10 microliters/h for 7 days, and withdrawal from
      pentobarbital was rendered 24 h after the stopping of the infusion. To eliminate
      the induction of hepatic metabolism by systemic administration of pentobarbital,
      an i.c.v. infusion model of tolerance to and withdrawal from pentobarbital was
      used. Little is known about the functional modulation of the G protein alpha
      subunits at the molecular level. The effects of continuous infusion of
      pentobarbital on the modulation of G protein alpha-subunits mRNA were
      investigated by using in situ hybridization study. In situ hybridization showed
      that the level of G alpha s mRNA was increased in the septum and brainstem, and
      the level of G alpha o mRNA was elevated in the cortex during the pentobarbital
      withdrawal. The level of G alpha i mRNA was significantly elevated in almost all
      area of brain during the pentobarbital withdrawal. These results suggest that
      region-specific changes of G protein alpha-subunit mRNA were involved in the
      withdrawal from pentobarbital, whereas alpha-subunit is not so highly involved in
      the pentobarbital tolerance.

PMID- 12199160
TI  - Dry central perforation with tympanosclerosis and cholesteatoma.

PMID- 12199161
TI  - An unusual medial ostium of a concha bullosa of the middle turbinate.

PMID- 12199162
TI  - Right posthemorrhagic polyp with vocal fold varices.

PMID- 12199164
TI  - Extramedullary plasmacytoma in the nasal cavity.

PMID- 12199163
TI  - A case of normal ENG findings on air caloric stimulus that were not substantiated
      by water stimulus.

PMID- 12199165
TI  - Hiatal hernia.

PMID- 12199166
TI  - Rhinoscleroma.

PMID- 12199167
TI  - Adenoid cystic carcinoma of the paranasal sinuses or nasal cavity: a 40-year
      review of 35 cases.
AB  - We retrospectively reviewed 35 cases of adenoid cystic carcinoma that had
      originated in the minor salivary glands of the paranasal sinuses or nasal cavity.
      All patients had been seen at two tertiary-care referral centers in western New
      York State between 1960 and 2000. Twenty patients had been treated with surgery
      and adjuvant radiotherapy, 10 patients with surgery alone, three with
      radiotherapy alone, and two with concurrent radiotherapy and chemotherapy. During
      the study, 22 patients developed recurrent disease--11 locally; three distantly;
      seven locally and distantly; and one locally, regionally, and distantly. At the
      conclusion of the study, 14 patients were alive and disease-free, and eight were
      alive with disease; 10 patients had died with disease, and three had died of
      other causes with no evidence of disease. Adenoid cystic carcinoma of the
      paranasal sinuses or nasal cavity is an aggressive neoplasm that results in a
      high incidence of both local recurrence and distant metastasis, regardless of
      treatment modality. Most cases are ultimately fatal, although long disease-free
      intervals have been observed. A combination of surgery and radiotherapy offers
      these patients the best chance for disease control.

PMID- 12199168
TI  - A rare case of mucoepidermoid carcinoma of the nasal cavity.
AB  - Mucoepidermoid carcinoma of the nasal cavity is rare. We report the case of a 57
      year-old man who was evaluated for a rapidly enlarging subcutaneous mass on the
      nasal bridge. The tumor was diagnosed as a mucoepidermoid carcinoma. The patient
      underwent extensive surgical resection and postoperative radiotherapy, but 5
      months later he required orbital exenteration for persistent disease. Despite
      these radical measures, the patient died with persistent disease 9 months
      following the initial evaluation. The aggressive behavior of this tumor
      highlights the need for physicians to be aware of the differential diagnosis,
      symptoms, and signs of neoplasms that originate in the nasal cavity so that
      prompt treatment can be instituted.

PMID- 12199169
TI  - Philately and otolaryngology.

PMID- 12199170
TI  - Free-radical damage: a possible mechanism of laryngeal aging.
AB  - We conducted a study of lipid peroxidation as a marker of age-related free
      radical damage in the human larynx--the first study of its kind. A colorimetric
      assay for malondialdehyde (MDA) and 4-hydroxy-2-nonenal (4-HNE) was performed on
      extracts taken from thyroarytenoid muscle harvested from fresh cadaveric
      laryngeal specimens. Levels of MDA and 4-HNE were measured by spectrophotometry.
      Correlation studies were performed by linear regression analysis. We found that
      MDA levels in human thyroarytenoid muscle appeared to increase with age while 4
      HNE levels showed a slight decrease with age. Our findings are consistent with
      those of previous studies of other organ systems and indicate that there is a
      need for further study of free-radical damage and the effects of aging on the
      human larynx and on voice production.

PMID- 12199171
TI  - Temporary balloon occlusion and ethanol injection for preoperative embolization
      of carotid-body tumor.
AB  - We report on the preoperative embolization of a carotid-body paraganglioma by
      temporary balloon occlusion and ethanol injection. Complete devascularization was
      achieved without complication. Resection after a short postembolization interval
      required artery sacrifice. Histologic evaluation revealed that the tumor
      contained diffuse ethanol-induced microemboli. Compared with unembolized and
      polyvinyl-alcohol-embolized carotid-body paragangliomas, our technique resulted
      in no greater adverse effects on the tumor-vessel interface. This procedure is an
      effective and promising method of preoperative embolization of carotid-body
      tumors and warrants further experience and study. In this article, we also review
      the literature on carotid-body tumor embolization and ethanol embolization.

PMID- 12199172
TI  - Experience with stapedectomy in a developing country: a review of 200 cases.
AB  - Since stapedectomy was first performed in 1956, many innovations have been
      described. We retrospectively analyzed 200 cases of stapedectomy that had been
      performed with standard otologic instruments. Of the 200 patients, 54 (27.0%) had
      significant sensory deafness associated with footplate fixation. In most cases,
      the footplate was partially removed (stapedotomy group); in the remainder, the
      footplate was removed in its entirety or subtotally (stapedectomy group). Of the
      200 patients, 163 were available for short-term follow-up. The air-bone gap was
      closed to within 10 dB in roughly 83% of both groups. Although long-term follow
      up was possible in only a limited number of cases, we believe that an experienced
      otologist working with standard equipment and a basic operating microscope can
      obtain satisfactory stapedectomy results with minimal complications.

PMID- 12199173
TI  - Complete vascular ring detected by barium esophagography.
AB  - The diagnosis of a vascular ring can be made on the basis of characteristic
      findings on barium esophagography. We report a case of a double aortic arch in a
      9-month-old girl that was diagnosed in this manner, and we briefly review the
      anatomic characteristics of vascular rings.

PMID- 12199174
TI  - Effectiveness of nonsurgical office closure of tympanic membrane pars tensa
      perforations.
AB  - We report on our experience with nonsurgical office closure of tympanic membrane
      pars tensa perforations with the little-used but well-established Derlacki
      method, a procedure that had been in general use before the introduction of
      tympanoplasty more than a half century ago. We describe our results--including a
      success rate of 84.2%--in treating 81 perforations during the 6-year span from
      1996 through 2001.

PMID- 12199175
TI  - Cocaine-induced oronasal fistulas with external nasal erosion but without palate
      involvement.
AB  - The effects of chronic cocaine abuse have been widely described in the
      literature. Common complications include nasal septal perforation, saddle-nose
      deformity, and palatal perforation. Erosion of the external structures of the
      face has not been as extensively described, nor have oronasal fistulas that
      involve structures other than the hard or soft palate. In this article, we
      present the first reported case of cocaine-induced external nasal erosion that
      included multiple oronasal fistulas in the anterior gingival sulcus but did not
      involve the hard or soft palate. We stress the importance of a thorough history
      in such patients and consideration of all possible diagnoses, including drug
      abuse.

PMID- 12199176
TI  - First report of a lipoblastoma of the parapharyngeal space.
AB  - Lipoblastoma is a rare benign tumor that occurs primarily in children younger
      than 3 years of age. Fewer than 100 cases have been reported in the literature,
      and only eight cases have been previously reported in the head and neck; two of
      them occurred in the parotid region, where the differential diagnosis becomes
      quite extensive. We report a new case of head and neck lipoblastoma--one that
      occurred in the parapharyngeal space, a site that has not been previously
      reported. By doing so, we hope to promote awareness and consideration of
      lipoblastoma in the differential diagnosis of deep-parotid and parapharyngeal
      space neoplasms.

PMID- 12199177
TI  - Report of a rare case of trauma-induced thyroid storm.
AB  - Thyroid storm is a potentially life-threatening endocrinologic emergency
      characterized by an exacerbation of a hyperthyroid state. Several inciting
      factors can instigate the conversion of thyrotoxicosis to thyroid storm; trauma
      is one such trigger, but it is rare. Patients with thyroid storm can manifest
      fever, nervous system disorders, gastrointestinal or hepatic dysfunction (e.g.,
      nausea, vomiting, diarrhea, and/or jaundice), and arrhythmia and other
      cardiovascular abnormalities. Treatment of thyroid storm is multimodal and is
      best managed by the endocrinologist and medical intensivist. Initial medical and
      supportive therapies are directed at stabilizing the patient, correcting the
      hyperthyroid state, managing the systemic decompensation, and treating the
      underlying cause. Once this has been achieved, definitive treatment in the form
      of radioactive ablation or surgery should be undertaken. We describe a case of
      thyroid storm in a young man that was precipitated by a motor vehicle accident.

PMID- 12199178
TI  - Spontaneous sublingual hematoma as a complication of severe hypertension: first
      report of a case.
AB  - We describe what we believe is the first reported case of a sublingual hematoma
      secondary to severe hypertension. The patient, a 77-year-old woman, experienced a
      spontaneous hematoma of the floor of the mouth, tongue, and sublingual space that
      eventually caused an airway obstruction. We performed an emergency tracheostomy
      under local anesthesia and then evacuated the hematoma through an incision along
      the floor of the mouth. The patient recovered uneventfully.

PMID- 12199180
TI  - Chronic suppurative otitis media in indigenous populations: the Australian
      aborigine.

PMID- 12199179
TI  - Extragonadal germ-cell tumor: a rare differential diagnosis of a cervical lump in
      a young man.
AB  - In this case report, we discuss the potential diagnostic difficulty of
      identifying the cause or origin of a cervical swelling, a clinical situation
      often encountered in otolaryngology patients. A 30-year-old man came to us with a
      painless left cervical lump that he had noticed 8 weeks earlier. A series of
      examinations--including various biopsies, computed tomography, and extensive
      staging procedures--could not establish the diagnosis. We eventually identified
      the mass as an extragonadal germ-cell tumor. The diagnosis was established only
      after additional serologic testing and detection of tumor markers specific for
      extragonadal germ-cell tumor.

PMID- 12199181
TI  - Perioperative antibiotics in chronic suppurative otitis media.

PMID- 12199182
TI  - Topical and systemic treatment for chronic suppurative otitis media.

PMID- 12199183
TI  - Update on topical ototoxicity in chronic suppurative otitis media.

PMID- 12199184
TI  - Topical quinolones in the treatment of chronic suppurative otitis media and
      recurrent otorrhea.

PMID- 12199185
TI  - Otitis externa: a clinical overview.

PMID- 12199186
TI  - Update on cerumen and ceruminolytics.

PMID- 12199187
TI  - Post-tympanostomy tube otorrhea in children: a clinical overview.

PMID- 12199188
TI  - Prophylactic therapy for post-tympanostomy tube otorrhea.

PMID- 12199189
TI  - Chronic suppurative otitis media: a clinical overview.

PMID- 12199190
TI  - Digital processing of radiographic images for print publication.
AB  - Digital imaging of X-rays yields high quality, evenly exposed negatives and
      prints. This article outlines the method used, materials and methods of this
      technique and discusses the advantages of digital radiographic images.

PMID- 12199192
TI  - [Superficial bladder tumors. Report of the 2001 Congress of the French
      Association of Urology].

PMID- 12199191
TI  - Coffee stain technique.
AB  - Backgrounds prepared with coffee grounds and Conte dust produce many unexpected
      patterns. The technique adds interest to artwork and is equally good for a
      carefully prepared drawing as it is for a quick, casual sketch. A materials list
      is provided which includes a variety of surface choices. The article provides
      step-by-step directions for the preparation of an attractive coffee-stained
      background, gives detailed instructions describing how to transfer a sketch,
      offers tips for drawing with Conte and carbon pencils and tells how to apply
      highlights.

PMID- 12199193
TI  - To web or not to web, that is no longer a question. Or, what is a web-driven
      scientific publication good for?

PMID- 12199194
TI  - Protection against meningitis-associated central nervous system complications by
      uric acid.

PMID- 12199195
TI  - [History of infusions].

PMID- 12199196
TI  - Obtaining credit reports can be risky business.

PMID- 12199197
TI  - Interview with professor Bin Kroon.

PMID- 12199198
TI  - [Diagnosis and therapy of celiac disease in adolescence and adulthood].
AB  - The incidence of celiac disease has increased considerably during the last two
      decades. Celiac Disease is now diagnosed in adults at least as frequently as in
      children. A prevalence of about 1:200 seems reasonable in central Europe. Besides
      the typical symptomatic presentation, silent, latent and potential celiac disease
      are found. Oligo- to asymptomatic courses (silent celiac disease) are
      increasingly found in all age groups. Endomysial antibodies and tissue
      transglutaminase antibodies are sensitive and specific for about 95% of celiac
      patients. However, the final diagnosis is only done by a - mostly endoscopical -
      biopsy from the distal part of the duodenum, demonstrating hyperplastic villous
      atrophy of the mucosa with increased numbers of intraepithelial lymphocytes. The
      biopsies should be classified histologically according to the modified Marsh
      criteria. Increased prevalence in family members (10 to 15%) and in associated
      diseases (e.g. diabetes mellitus) lead to the recommendation of active screening
      in populations at risk. Although the clinical symptoms are rather variable and
      different, the response to a lifelong strict gluten free diet is nearly 100%. So
      called refractory celiac disease is very rare. There are numerous associated
      diseases as dermatitis herpetiformis, diabetes mellitus type I, thyroid and
      neurologic diseases. The most frequent complications are retardation of growth in
      childhood, early onset osteoporosis, and an increased risk of abortions. The most
      severe complication is intestinal lymphoma. Especially patients with late
      diagnosis and bad dietary adherence are at risk. A regular follow-up of patients,
      rather with antibody tests than with duodenal biopsies is recommended to test and
      secure dietary compliance.

PMID- 12199199
TI  - Further comments on the bioavailability of D4.

PMID- 12199201
TI  - Rising from the ashes: NIEHS awards post-WTC grants.

PMID- 12199200
TI  - Bad grades for school buses.

PMID- 12199202
TI  - Impingement of the supraceliac aorta after a gun shot wound.

PMID- 12199203
TI  - Traumatic left renal arterioureteral fistula.

PMID- 12199204
TI  - Immunogenicity of a recombinant fusion protein of tandem repeat epitopes of foot
      and-mouth disease virus type Asia 1 for guinea pigs.
AB  - In this study, the sequences of capsid protein VPI regions of YNAs1.1 and YNAs1.2
      isolates of foot-and-mouth disease virus (FMDV) were analyzed and a peptide
      containing amino acids (aa) 133-158 of VP1 and aa 20-34 of VP4 of FMDV type Asia
      I was assumed to contain B and T cell epitopes, because it is hypervariable and
      includes a cell attachment site RGD located in the G-H loop. The DNA fragments
      encoding aa 133-158 of VP1 and aa 20-34 of VP4 of FMDV type Asia 1 were
      chemically synthesized and ligated into a tandem repeat of aa 133-158-20
      approximately 34-133-158. In order to enhance its immunogenicity, the tandem
      repeat was inserted downstream of the beta-galactosidase gene in the expression
      vector pWR590. This insertion yielded a recombinant expression vector pAS1
      encoding the fusion protein. The latter reacted with sera from FMDV type Asia 1
      infected animals in vitro and elicited high levels of neutralizing antibodies in
      guinea pigs. The T cell proliferation in immunized animals increased following
      stimulation with the fusion protein. It is reported for the first time that a
      recombinant fusion protein vaccine was produced using B and T cell epitopes of
      FMDV type Asia 1 and that this fusion protein was immunogenic. The fusion protein
      reported here can serve as a candidate of fusion epitopes for design of a vaccine
      against FMDV type Asia 1.

PMID- 12199205
TI  - Selection and expression of peptides which can change the conformation of p20
      protein of rice stripe virus.
AB  - Phages with high affinity to the P20 protein of rice stripe virus (RSV) were
      enriched from phage-displayed random 12-mer peptide library after three rounds of
      phage display screening. Nine different peptides from the enriched library were
      selected by enzyme-linked immunosorbent assay (ELISA). The P20 protein from raw
      extracts of rice leaves infected with RSV could be detected by those 9 peptides
      displayed on the phage, which suggested that a peptide could be an effective tool
      for diagnosis of RSV in rice and planthopper. Circular dichroism (CD) spectra of
      P20 fusion proteins with the binding phages and non-binding phages showed that
      the conformation of P20 protein was changed after binding to each of the 9
      selected 12-mer peptides, which suggested that these peptides might disrupt the
      function of the P20 protein. Thereafter, those peptides might be used to develop
      plant resistance and disrupt virus transmission. Three of the 12-mer peptide
      genes were fused with the glutathione-S-transferase (GST) gene in the vector pGEX
      3X. The fusion proteins were obtained from an Escherichia coli expression system
      and purified. The fusion proteins might have a potential to develop a plant
      peptide-based resistance to its pathogens and virus diagnosis. It also provided a
      tool (i) to confirm the inhibition of the function of P20 protein by the fusion
      peptides in vivo, and (ii) to detect the function of P20 protein and the
      interaction between the virus and its vector.

PMID- 12199206
TI  - Computational analyses in cognitive neuroscience: in defense of biological
      implausibility.
AB  - Because cognitive neuroscience researchers attempt to understand the human mind
      by bridging behavior and brain, they expect computational analyses to be
      biologically plausible. In this paper, biologically implausible computational
      analyses are shown to have critical and essential roles in the various stages and
      domains of cognitive neuroscience research. Specifically, biologically
      implausible computational analyses can contribute to (1) understanding and
      characterizing the problem that is being studied, (2) examining the availability
      of information and its representation, and (3) evaluating and understanding the
      neuronal solution. In the context of the distinct types of contributions made by
      certain computational analyses, the biological plausibility of those analyses is
      altogether irrelevant. These biologically implausible models are nevertheless
      relevant and important for biologically driven research.

PMID- 12199207
TI  - Feature integration that routinely occurs without focal attention.
AB  - To analyze visual scenes, the visual system decomposes the visual scene into
      features that are processed in parallel by separate subsystems. Certain theories
      (Treisman, Wolfe) propose that these subsystems function independently before
      focal attention integrates their output. We describe a new paradigm-the gestalt
      detection task--that directly assesses the degree of preattentive dependence
      between any two subsystems. We present five experiments that test whether the
      subsystems that process form and color function independently in processing brief
      (and, therefore, preattentively processed) stimuli. Our data show that these two
      subsystems interact during the preattentive processing of feature-dependent
      information. They are synergistic when the information they receive is
      consistent; they are antagonistic when the information they receive is
      inconsistent.

PMID- 12199210
TI  - Fechnerian metrics in unidimensional and multidimensional stimulus spaces.
AB  - A new theory is proposed for subjective (Fechnerian) distances among stimuli in a
      continuous stimulus space of arbitrary dimensionality. Each stimulus in such a
      space is associated with a psychometric function that determines probabilities
      with which it is discriminated from other stimuli, and a certain measure of its
      discriminability from its infinitesimally close neighboring stimuli is computed
      from the shape of this psychometric function in the vicinity of its minimum. This
      measure of discriminability can be integrated along any path connecting any two
      points in the stimulus space, yielding the psychometric length of this path. The
      Fechnerian distance between two stimuli is defined as the infimum of the
      psychometric lengths of all paths connecting the two stimuli. For a broad class
      of models defining the dichotomy of response bias versus discriminability, the
      Fechnerian distances are invariant under response bias changes. In the case in
      which physically multidimensional stimuli are discriminated along some
      unidimensional subjective attribute, a systematic construction of the Fechnerian
      metric leads to a resolution of the long-standing controversy related to the
      numbers of just-noticeable differences between isosensitivity curves. It is
      argued that for unidimensional stimulus continua, the proposed theory is close to
      the intended meaning of Fechner's original theory.

PMID- 12199209
TI  - Assessing sensitivity in a multidimensional space: some problems and a definition
      of a general d'.
AB  - This article provides a formal definition for a sensivity measure, d'g between
      two multivariate stimuli. In recent attempts to assess perceptual representations
      using qualitative tests on response probabilities, the concept of a d' between
      two multidimensional stimuli has played a central role. For example, Kadlec and
      Townsend (1992a, 1992b) proposed several tests based on multidimensional signal
      detection theory that allow conclusions concerning the perceptual and/or
      decisional interactions of stimulus dimensions. One proposition, referred to as
      the diagonal d' test, relies on specific stimulus subsets of a feature-complete
      factorial identification task to infer perceptual separability. Also, Ashby and
      Townsend (1986), in a similar manner, attempted to relate perceptual independence
      to dimensional orthogonality in Tanner's (1956) model, which also involves d'
      between two multivariate signals. An analysis of the proposed d'g reveals
      shortcomings in the diagonal d' test and also demonstrates that the assumptions
      behind equating perceptual independence to dimensional orthogonality are too
      weak. This d'g can be related to a common measure of statistical distance,
      Mahalanobis distance, in the special case of equal covariance matrices.

PMID- 12199208
TI  - Visuospatial attention: beyond a spotlight model.
AB  - Much of the research in visual attention has been driven by the spotlight
      metaphor. This metaphor has been useful over many years for generating
      experimental questions in attention research. However, theories and models of
      visual selection have reached such a level of complexity that debate now centers
      around more specific questions about the nature of attention. In this review, the
      general question "Is visual attention like a spotlight?" is broken down into
      seven specific questions concerning the nature of visual attention, and the
      evidence relevant to each is examined. The answers to these specific questions
      provide important clues about why visual selection is necessary and what purpose
      attention plays in visual cognition.

PMID- 12199211
TI  - Response time distributions: some simple effects of factors selectively
      influencing mental processes.
AB  - When hypotheses about mental processing are tested with response times,
      inferences are often based on means, and occasionally on variance or skewness.
      Calculations on entire distributions of response times are more informative and
      can be conveniently carried out. Recently investigators have been updating
      procedures primarily based on means (such as additive factors tests) to
      procedures employing entire distribution functions. In one such advance, Nozawa
      and Townsend upgraded earlier tests of whether factors selectively influence
      serial or parallel processes, and whether parallel processes enter AND gates or
      OR gates. We discuss generalizations of the tests to complex arrangements of
      processes in networks. Results for a particularly difficult network, the
      Wheatstone bridge, are presented here. We use simulations to demonstrate the
      feasibility of the tests, and the possibility of mimicking.

PMID- 12199212
TI  - A note on the influence of grouping on illusory contours.
AB  - It is well known that dots superimposed on the Koffka cross change the shape of
      the illusory surface. It has been claimed, but never proved, that this effect is
      due to the shape of the virtual figure inwhich the dots organize. In this note it
      is proved that the shape of the virtual figure is indeed the crucial factor. In
      fact, the shape of the illusory surface changes if the way in which the dots
      organize is altered by adding other dots; if, then, the former organization is
      restored by adding further dots, the illusory shape is restored too, at least to
      a large extent.

PMID- 12199214
TI  - Sequential effects in auditory choice reaction time tasks.
AB  - This paper concerns sequential effects in choice reaction time tasks. Performance
      in two interleaved auditory tasks was examined, and two general types of
      sequential effects were revealed. First, a response repetition effect occurred:
      Subjects were facilitated in responding when both the stimulus and the response
      were immediately repeated. Generally, it appeared that subjects were operating
      according to the bypass rule--that is, repeat the response if the stimulus or
      some aspect thereof is repeated from the preceding trial; otherwise, change the
      response. In addition, the experiment also revealed a second type of sequential
      effect, known as a task-switching effect Subjects were overall slower to respond
      when the task changed between adjacent trials than when there was no task change.
      A final result was that subjects were markedly impaired when the stimulus changed
      but the same response had to be repeated. This finding has been reported
      elsewhere when purely visual tasks have been used. Hence, it seems that
      particular difficulties arise, in such sequential testing situations, when type
      distinct stimuli are grouped into the same response categories.

PMID- 12199213
TI  - Effects of attention on localization of stimuli in the visual field.
AB  - Subjects localized a small letter that appeared inside one of three large circles
      that was either validly or invalidly cued. The results indicated that, although
      unattended stimuli were localized fairly accurately, attention still improved
      localization. Moreover, the results revealed a greater dispersion of localization
      responses along the horizontal axis and also showed that mislocalization of
      attended peripheral stimuli is biased toward the periphery.

PMID- 12199215
TI  - Response conflict reverses priming: a replication.
AB  - Subjects named target words that followed a masked prime word of 33-msec
      (Experiments 1A and 1B) or 200-msec (Experiment 2) duration. The target word was
      either presented alone or accompanied by an interleaved distractor word. Targets
      presented alone were named more quickly following an identical prime than
      following an unrelated prime (repetition priming). In Experiment 1A, targets with
      distractors were named more slowly following an identical prime than following an
      unrelated prime (negative priming), replicating Milliken, Joordens, Merikle, and
      Seiffert (Psychological Review, 1998). In Experiments 1B and 2, repetition
      priming was reduced, although not reversed, for targets with distractors. The
      results of all three experiments are opposite to the usual finding of enhanced
      priming for perceptually degraded targets and suggest that response conflict
      engages retrospective mechanisms that counteract the facilitatory effects of
      priming.

PMID- 12199216
TI  - The role of familiarity in recognition.
AB  - The role of familiarity in recognition was investigated by having subjects study
      a list of stimuli, some of which had been presented earlier in the experiment.
      The number of positive responses, both to targets and distractors, increased as a
      result of this familiarization process. This familiarization process had a
      greater effect on false alarms than on hits, so that recognition accuracy was
      lower for familiar stimuli than for relatively novel stimuli. This pattern of
      results differs from that found in most experiments studying the effects of
      linguistic word frequency on recognition.

PMID- 12199217
TI  - Individual differences in imagination inflation.
AB  - Garry, Manning, Loftus, and Sherman (1996) found that when adult subjects
      imagined childhood events, these events were subsequentlyjudged as more likely to
      have occurred than were not-imagined events. The authors termed this effect
      imagination inflation. We replicated the effect, using a novel set of Life Events
      Inventory events. Further, we tested whether the effect is related to four
      subject characteristics possibly associated with false memory creation. The
      extent to which subjects inflated judged likelihood following imagined events was
      associated with indices of hypnotic suggestibility and dissociativity, but not
      with vividness of imagery or interrogative suggestibility. Results suggest that
      imagination plays a role in subsequent likelihood judgments regarding childhood
      events, and that some individuals are more likely than others to experience
      imagination inflation.

PMID- 12199218
TI  - Base-rate training without case cues reduces base-rate neglect.
AB  - Base-rate neglect is a persistent phenomenon in which subjects do not place
      sufficient weight on the probabilities of occurrence of relevant events. Two
      experiments with college students support the hypothesis that base-rate neglect
      may be minimized by providing base-rate training in the absence of case, or
      witness, cues, prior to introducing (or reintroducing) these cues. In Experiment
      1, the hypothesis was supported by both within-subjects and between-groups
      assessments; in Experiment 2, the hypothesis was supported while the effects of
      instructions and a correction procedure were found to be minimal. In Experiment
      1, but not in Experiment 2, training with case cues present also reduced base
      rate neglect, but this effect was not sufficient to account for the effect of cue
      absent base-rate training. Correction trials led some subjects to detect that the
      task contingencies were random; however, neither this nor actually telling
      subjects after the experiment that the task was indeed random led invariably to
      subjects' describing the optimal strategy (which was to choose the richer
      alternative exclusively).

PMID- 12199219
TI  - Asymmetries of comparison.
AB  - Tversky's (1977) seminal work on directionality injudgments of similarity
      demonstrated that people may not judge the similarity of A to B to be equal to
      the similarity of B to A. In a series of studies, we investigated comparison
      asymmetries. In Experiment 1, our aim was to extend Tversky's findings to a
      heterogeneous stimulus set, but no reliable asymmetries were observed. Experiment
      2 employed a variety of comparison judgments, and, although some of these
      measures showed asymmetries, we still failed to observe asymmetries in rated
      similarity. A final attempt to obtain asymmetries used direction as a within
      subjects factor, and for the first time, rating asymmetries were observed. Our
      data reinforce the idea of comparison asymmetries but suggest that similarity
      rating asymmetries are only observed under quite circumscribed conditions.

PMID- 12199220
TI  - Domain differences in absolute judgments of category membership: evidence for an
      essentialist account of categorization.
AB  - There has been some debate about the correspondence between typicality gradients
      and category membership. The present study investigates the relationship between
      these two measures in the domains of animals and artifacts. Forty-two adults
      judged the degree of typicality or category membership of 293 animals and
      artifacts. The subjects' tendency for animals, but not for artifacts, was to make
      more absolute ratings on category membership (i.e., judging exemplars as
      definitely members or definitely not members of their respective category) than
      on typicality. More importantly, at almost every level of typicality, subjects
      were more likely to make absolute judgments of category membership for animals
      than for artifacts. These results indicate that people treat category membership
      of animals as relatively absolute (which best fits an essentialist model of
      categorization) and treat category membership of artifacts as relatively graded
      (which best fits a prototype model of categorization). These domain differences
      add crucial supporting evidence for claims about the domain-specificity of
      essentialism.

PMID- 12199221
TI  - Only the shadower knows: comment on Hamburger and Slowiaczek (1996).
AB  - The phonological priming effect may reflect basic processes in spoken word
      perception and has thus been a central topic of recent research. In this journal,
      Hamburger and Slowiaczek (1996) reported phonological priming data collected in a
      shadowing task. They replicated a prior study (Slowiaczek & Hamburger, 1992), but
      added new procedures to minimize bias. After observing inhibitory priming in a
      "low-expectancy" condition, they concluded that facilitatory priming reflects
      perceptual/response bias, but that inhibitory priming reflects automatic
      processes of lexical access. This commentary critiques Hamburger and Slowiaczek's
      method and presents new data that demonstrate persistent biases in primed
      shadowing. I suggest that such biases reflect natural, context-sensitive
      listening strategies.

PMID- 12199222
TI  - The Minnesota Project: the influence of American medicine on the development of
      medical education and medical research in post-war Korea.

PMID- 12199223
TI  - [Dr. Yoo Suk-Chang as a physician].
AB  - Dr. Yoo Suk - Chang (1900 - 1972) has been praised for his contribution to the
      development of the Korean society as an educator and an agricultural reformer as
      well as a physician. This paper describes his medical career, mainly his
      contribution to establish and administrate the Min - Jung Hospital (The People's
      Hospital) and publish a medical paper entitled Bokun Sibo (The Doctors' News) in
      the Colonial Period. I appreciate such his effort as the embodiment of his idea,
      "medical care for his people" and the medical reform in that period. I think his
      services as a physician correspond well with the activities against Japanese
      imperialism in his early age and the contribution to the education and
      agricultural reform in his late age. I stress that his medical achievement should
      not be supposed to be only his own, because it is not possible without the help
      of all his supporter - colleagues and the people.

PMID- 12199224
TI  - Informed consent for research is related to basic legal rights of all
      individuals.

PMID- 12199225
TI  - New oversight agency proposed for human research subjects.

PMID- 12199226
TI  - University's Multiple Project Assurance (MPA) could be renewed for only short
      periods of time.

PMID- 12199227
TI  - Court said IRB had too much power to make consent decisions for minors.

PMID- 12199228
TI  - Are there no per se disabilities under the Americans with Disabilities Act? The
      fate of asymptomatic HIV disease.

PMID- 12199229
TI  - End-of-life decision making: what we don't know, we make up; what we do know, we
      ignore.

PMID- 12199230
TI  - Cross-cultural issues in medicine.
AB  - Physicians in Canada are often required to practise cross-cultural medicine. This
      often leads to difficult ethical situations. Many of our medical decisions are
      based on values and beliefs about health that are uniquely tied to our culture.
      Although the temptation to assume they are universal is powerful, even our most
      basic ethical principles can be challenged. Female circumcision provides an
      interesting example of a conflict between our sense of beneficence and the desire
      to respect patient autonomy. Further problems arise with different
      interpretations of concepts such as individual human rights, informed consent and
      the value of human life. Physicians must recognize the potential for such
      conflict and work to achieve a better understanding of the issues relevant to
      each cultural group.

PMID- 12199231
TI  - Human rights, doctors' rights, and patients' rights/Droits humains, droits des
      medicins et des malades.

PMID- 12199232
TI  - Should human cloning be permitted?

PMID- 12199233
TI  - Reproductive technology comes of age.

PMID- 12199234
TI  - A Jewish approach to assisted reproductive technologies.

PMID- 12199235
TI  - Essay: the issue of justice in reproductive matters.

PMID- 12199236
TI  - Economics versus ethics in reproductive medicine.

PMID- 12199237
TI  - The egg donor and surrogacy controversy: legal issues surrounding representation
      of parties to an egg donor and surrogacy contract.

PMID- 12199238
TI  - Considerations in surrogacy contracts.

PMID- 12199239
TI  - Family law conundrums in assisted reproduction.

PMID- 12199240
TI  - Community-based public health looks to law enforcement as a partner.

PMID- 12199241
TI  - Physician-assisted suicide--Michigan's temporary solution.

PMID- 12199242
TI  - The "non-declarant" in a PVS: adventures in Ohio's legal wonderland.

PMID- 12199243
TI  - Ethical and legal issues in the individual's right to die.

PMID- 12199244
TI  - Punishing assisted suicide: where legislators should fear to tread.

PMID- 12199245
TI  - The persecution and prosecution of Doctor Death and His Mercy Machine.

PMID- 12199246
TI  - "The legal response to assisted suicide".

PMID- 12199247
TI  - "The death of a person: ethics, the practice of medicine, and the law".

PMID- 12199248
TI  - Law reform.

PMID- 12199249
TI  - Hospice philosophy: an alternative to assisted suicide.

PMID- 12199250
TI  - Personal autonomy and physician-assisted suicide: the appropriate response to a
      modern ethical dilemma.

PMID- 12199251
TI  - The case against legal assisted suicide.

PMID- 12199252
TI  - State v. Chabot: a euthanasia case from the Netherlands.

PMID- 12199253
TI  - Extraterrestrial vestibular research, a new partial field of medical research
      into the human vestibular apparatus.
AB  - The first otologic professorial chair in the world was established by Politzer in
      Vienna as long ago as 1861. In 1914 an assistant of the 1st Vienna Ear Clinic
      with Politzer as its head, Barany, was awarded the Nobel Prize for Medicine for
      his fundamental investigations into the organ of equilibration and for his
      discovery of the caloric sensitivity of the semicircular canals. Since that time
      Barany is regarded as the founder of the physiology of the vestibular apparatus.
      During the period 1959 to 1963 a new conception of fundamental research into the
      vestibule was demanded and elaborated in Vienna with the postulate that, in all
      theoretical deliberations and practical experience, one should take into
      consideration that our experiments into the vestibule do not take place on a
      static platform but rather on a diversely moving one, namely the surface of the
      earth. This led to new findings in the field of research into the otolith
      apparatus. In 1962 it was discovered that the gravitation of the sun at the
      distance of earth-sun represents a supraliminal stimulus, namely both in the
      aphelion as well as in the perihelion position of the earth. In 1965 it was
      suggested in Vienna that a new branch of research into the vestibule should be
      established on an international level, the so-called extraterrestrial vestibular
      research. The importance of this new branch of research is discussed for all
      problems of orientation of human beings in space.

PMID- 12199254
TI  - In defense of whole-brain definitions of death.

PMID- 12199255
TI  - Medicine as a moral art: the Hippocratic philosophy of Herbert Ratner, M.D.

PMID- 12199256
TI  - Brain-based determination of death revisited.

PMID- 12199257
TI  - On artificial Martian conditions reproduced for microbiological research.
AB  - 1. It is of interest to investigate the behaviour of the terrestrial
      microorganisms under artificial Martian conditions. This will help to verify the
      hypothesis concerning a possibility of life on this planet. 2. An artificial
      climate chamber enables one to expose microbial cells to a simultaneous effect of
      such factors as temperature, pressure, gas composition and insolation: a)
      Temperature regime is maintained automatically by means of an electronic
      mechanical programme device. b) A sealed chamber insures a permanent gas mixture
      pressure equal to 0.1 atm. c)The spectral composition of light source is close to
      that of the sun spectrum. d)The chamber enables to expose microorganisms on
      membrane filters with diameter of 23 mm or in special quartz cells of the same
      diameter size. 3. The preliminary experiments have shown that not all the
      terrestrial forms of microorganisms do survive under artificial conditions of the
      Martian summer.

PMID- 12199258
TI  - Bacterial ecologies in limonite.
AB  - Limonite (Fe2O3 . nH2O) may be a constituent of the Martian surface. We have
      prepared culture media with ferric hydroxide as an electron acceptor. One medium
      contained ethanol, another gaseous hydrogen and carbon dioxide. Bacterial growth
      without light and oxygen suggests that ferric iron serves as a terminal
      respiratory electron acceptor. The oxidation of ferrous hydroxide may be carried
      out by photosynthetic bacteria. A ferrous-ferric couple may thus support
      bacterial respiration and photosynthesis in the absence of oxygen. This cycle may
      account for the dark markings of Mars.

PMID- 12199259
TI  - On the biological problems to be attacked with a series of U.S. satellites in
      1966.
AB  - In the opinion of interested biologists in the U.S. the search for
      extraterrestrial life is by far the outstanding biological task that can be
      undertaken with the new technology of spacecraft. And it is their hope that the
      bulk of the national effort put into biology in space will be directed towards
      the biological exploration of Mars. There are, however, many other issues that
      the biologist can and should pursue in orbiting laboratories, or satellites. 1)
      Some of these are in the areas of the cardiovascular and neurophysiology of
      primates, and derive their importance from the need to put man into the
      weightless state for prolonged durations. 2) Other questions, similarly prompted
      by the prospect of prolonged space flight, concern the radiation hazard. Many
      experiments are planned for a single satellite in which it is hoped to discover
      whether the weightless state significantly affects biological responses to
      radiation. If, as is expected, there is no synergism between weightlessness and
      radiation, it will be possible to pursue all other questions about radiation
      effects in space by experimentation on the ground. 3) Two other classes of
      questions that satellite experiments may answer have deeper roots in theoretical
      and cellular physiology. The first of these concerns weightlessness itself. A
      long list of experiments involving a diversity of material from animal eggs to
      higher plants will seek to determine whether or not the absence of a
      gravitational input to the system significantly affects its general performance.
      Special interest in the U.S. attaches to suggestions from ground based
      experiments that normal morphogenesis may fail in plant systems that are exposed
      to less than about 10(-5) g. 4) It is also hoped that satellite experiments will
      help resolve the long-standing debate on the cause of persistent daily
      rhythmicity in organisms. One school of workers in the U.S. continues to believe
      that such rhythmicity is caused by organisms sensing an unidentified physical
      variable with a 24 hr period and hence presumably caused by the earth's rotation.
      It is proposed to assay the persistence and stability of such rhythms in
      organisms orbiting the earth with a period of about 90 min. Persistence of the
      rhythm in such orbital conditions would dispose of the theory of external
      causation; failure of such rhythms to persist would, however, constitute strong
      though not crucial support in its favor.

PMID- 12199260
TI  - The NASA Biosatellite Program.
AB  - The United States Biosatellite Program includes critical and sophisticated
      experiments to study the effects of weightlessness and decreased gravity at the
      cellular, tissue, organ, and organism levels during orbital periods of 3 to 30
      days. The experiments involve a wide variety of plants and animals from single
      celled organisms to primates. The effects of weightlessness combined with a known
      source of radiation will be studied to determine if there are any antagonistic or
      synergistic genetic or somatic effects on various organisms. Experiments are
      included to study the effect of removal from the Earth's rotation in relation to
      biological rhythms of organisms. The experimental test organisms have been
      exposed to the simulated dynamic forces of launch and flight profiles.

PMID- 12199262
TI  - Oral transmucosal fentanyl: new preparation. For breakthrough cancer pain when
      morphine fails.
AB  - (1) Some cancer patients suffer occasional breakthrough pain despite well
      conducted opiate treatment, warranting the use of immediate-release oral
      morphine. (2) A fentanyl preparation for oral transmucosal administration has
      just been granted this indication in France. (3) The evaluation file mainly
      contains results from a randomised double-blind cross-over trial comparing
      transmucosal fentanyl with oral morphine tablets in cancer patients. It showed a
      small gain in terms of rapidity and efficacy of pain relief with fentanyl
      relative to morphine, but this was of dubious clinical relevance. (4) The adverse
      effects of oral transmucosal fentanyl are those of all opiates, such as
      drowsiness, dizziness, nausea, vomiting and confusion. (5) The oral transmucosal
      fentanyl preparation has the taste and appearance of a lollipop, and may
      therefore be attractive to children. The packaging seems to take this risk into
      account, but precautions must be taken to keep this treatment away from children,
      especially after opening. (6) Immediate-release oral morphine remains the
      standard treatment for breakthrough pain in patients receiving opiate therapy. If
      it is inadequate, oral transmucosal fentanyl may sometimes be slightly better.

PMID- 12199261
TI  - Trimetazidine: a second look. Still no efficacy in visual disorders.
AB  - (1) The current French indications for trimetazidine in loss of visual acuity and
      visual field disorders of presumed vascular origin cover a plethora of
      ophthalmological and neurological disorders. (2) The rare published clinical
      trials, all of which are flawed, fail to prove the efficacy of trimetazidine for
      these indications. (3) Data on adverse reactions to trimetazidine are inadequate.
      Rare but serious side effects cannot be ruled out. (4) Trimetazidine-based
      preparations are costly, especially given their doubtful benefit. (5) In
      practice, trimetazidine is no more than a placebo in its ophthalmological uses.
      In our opinion, the risk of side effects (albeit low) and the possibility that a
      trimetazidine prescription may reduce elderly patients' adherence to other, truly
      beneficial treatments, mean that prescribers should simply ignore these products.

PMID- 12199263
TI  - Selegiline: a second look. Six years later: too risky in Parkinson's disease.
AB  - (1) The reference treatment for Parkinson's disease is levodopa plus a peripheral
      dopadecarboxylase inhibitor (benserazide or carbidopa). (2) In 1996, selegiline,
      a type B MAOI marketed in France since 1988, saw its indications extended to
      cover single-agent therapy of early-stage Parkinson's disease, and in combination
      with levodopa, before onset of complications of levodopa therapy. The initial
      clinical file failed to show that selegiline had any benefit in these
      indications. (3) Now, in 2002, new data from trials involving hundreds of
      untreated patients show that selegiline postpones the need for levodopa therapy
      for a few months but fails to substantially alter the progression of Parkinson's
      disease. (4) A clinical trial and a retrospective epidemiological study of
      patients with advanced Parkinson's disease showed excess mortality on selegiline.
      (5) The side effects of selegiline are similar to those of other antiparkinsonian
      drugs and amphetamine. Notable side effects include cardiovascular problems
      (postural hypotension, atrial fibrillation and arterial hypertension). (6)
      Selegiline can cause a serotoninergic syndrome and arterial hypertension, so must
      not be combined with pethidine, tramadol, bupropion, sumatriptan, zolmitriptan or
      naratriptan. Concurrent treatment with serotonin reuptake inhibitor
      antidepressants should also be avoided. (7) Given the only moderate effects of
      selegiline in Parkinson's disease, and the possibility of a slight increase in
      mortality, there is no justification for prescribing this medication in patients
      with Parkinson's disease. (8) Whatever the stage of Parkinson's disease, there is
      no justification for starting patients on selegiline. Patients who are already
      taking selegiline should only continue to take it if they feel a clear benefit
      and are free from risk factors for early mortality, especially cardiovascular
      disease.

PMID- 12199264
TI  - Gabapentin: new indication. In postherpetic neuralgia when amitriptyline fails.
AB  - (1) Postherpetic pain is infrequent, but the incidence increases with age. (2)
      The reference treatment for postherpetic pain is oral amitriptyline or
      desipramine. (3) Gabapentin, an antiepileptic agent, is the first drug to be
      granted specific approval in France for the treatment of postherpetic pain. (4)
      In two placebo-controlled trials, gabapentin at a dose of between 1 800 and 3 600
      mg/day halved the intensity of pain in about one in three patients. In
      comparison, pain improved in about 50% of patients taking amitriptyline in
      clinical trials. (5) Both gabapentin and amitriptyline provoke sedation, but
      dizziness and peripheral oedema are more frequent on gabapentin, while atropinic
      effects predominate with amitriptyline. (6) Daily treatment is 10 times more
      costly in France. (7) In practice, the standard treatment of postherpetic pain
      remains oral amitriptyline or desipramine. Gabapentin is an alternative, given
      its different safety profile.

PMID- 12199265
TI  - NSAIDs and female infertility.
AB  - (1) There have been isolated reports of reversible female infertility linked to
      NSAIDs. The likely mechanism is ovulatory failure due to non rupture of mature
      follicles. (2) If a woman who presents with infertility is found to be taking a
      NSAID, the role of the drug should be considered before launching costly,
      invasive investigations or starting medically assisted reproduction.

PMID- 12199267
TI  - Side effects of levofloxacin.

PMID- 12199266
TI  - Venous thrombosis with cyproterone.
AB  - Do not use cyproterone-based pills as first-line oral contraceptive.

PMID- 12199268
TI  - Opacification of ocular implants.

PMID- 12199269
TI  - Hallucinations and Zolpidem.

PMID- 12199270
TI  - Death on bupropion (ex amfebutamone).

PMID- 12199271
TI  - Deaths linked to medical beds.

PMID- 12199272
TI  - Cardiac disorders and sibutramine.

PMID- 12199273
TI  - DHEA: the last elixir.
AB  - (1) DHEA, or dehydroepiandrosterone, is an adrenal steroid. Its physiological
      role is unclear, but it is known to be an intermediate in sex hormone synthesis.
      DHEA replacement therapy is not currently indicated in adrenal insufficiency. (2)
      Plasma DHEA levels are so low in most animal species that they are difficult to
      measure, hindering studies of the impact of DHEA on ageing. Most animal studies
      are based on administration of pharmacological doses. (3) Clinical data have been
      obtained in a very large number of observational studies, in which plasma
      concentrations of DHEA were measured in various situations. The only established
      fact is that circulating concentrations show wide interpersonal variability and a
      tendency to fall with age. Low DHEA levels have not so far been linked to any
      specific health disorders. (4) Clinical trials of DHEA have focused on cognitive
      function, well-being, libido, immunostimulation, etc. There is no proof that DHEA
      is beneficial in these areas. (5) The side effects of DHEA are linked to its
      androgenic effects (acne, hirsutism), its unfavourable effects on lipid
      metabolism (a cardiovascular risk factor), and a possible growth-stimulating
      effect on hormone-dependent malignancies (prostate, breast). (6) In practice,
      there is currently no scientific reason to prescribe DHEA for any purpose
      whatsoever.

PMID- 12199274
TI  - Stable severe asthma: vaccinate against influenza. Protect against exacerbation.
AB  - According to a study of nearly 2 000 asthmatic patients, influenza immunisation
      induces no serious short-term effects on respiratory function when the asthma is
      stable at the time of vaccination

PMID- 12199275
TI  - Repetitive publication.

PMID- 12199276
TI  - Oral pilocarpine: new preparation. Xerostomia after radiation therapy: moderately
      effective but costly.
AB  - (1) Dry mouth (xerostomia) is a frequent complication of radiation therapy for
      cancers of the ear nose and throat. Local measures such as saliva substitutes and
      anetholtrithione are either moderately effective, inadequately evaluated or
      little better than placebo. (2) Marketing authorization has been granted in
      France for an oral formulation of pilocarpine, an old parasympathomimetic agent,
      in the treatment of radiotherapy-induced xerostomia. (3) According to the results
      of two double-blind trials, pilocarpine (15-30 mg/day) improves symptoms in about
      50 % of patients, compared to improvement in 25% of patients taking placebo. The
      drug is slow to take effect and has little impact on daily life. It is not known
      whether pilocarpine helps prevent the complications of xerostomia. (4) Most
      adverse effects of pilocarpine are due to its parasympathomimetic effects, such
      as sweating, urinary frequency, flushing, rhinitis and nausea. Pilocarpine must
      therefore be used with caution in patients with asthma, cardiac arrhythmia,
      iridocyclitis, and closed-angle glaucoma. (5) In France, this pilocarpine
      formulation costs 18 times more than a preparation of pilocarpine 2% eye drops
      used orally (off licence). (6) In practice, patients needing symptomatic
      treatment of xerostomia after radiotherapy may benefit from oral pilocarpine but,
      given its limited efficacy and its adverse effects, other local treatments should
      be tried first.

PMID- 12199277
TI  - HIV-infected prisoners: what mental health services are constitutionally
      mandated?
AB  - State and federal correctional facilities currently have approximately 23,000
      inmates who are infected with human immunodeficiency virus (HIV). These inmates
      suffer from the same mental health disorders as uninfected inmates but are
      additionally subject to mental health problems uniquely related to their HIV
      infection. Many prison systems are struggling to provide minimal mental health
      care to uninfected inmates. How will prisoners address the additional mental
      health needs of the staggering number of inmates being diagnosed with AIDS and
      HIV? This article describes the type of mental health services that are
      constitutionally mandated and discusses whether and how prisons will have to
      respond to the distinct mental health issues related to HIV infection.

PMID- 12199278
TI  - Bioethics and the scientific challenge of the third millennium: to defend life,
      obey God and His natural laws.

PMID- 12199280
TI  - Human cloning: position paper of the Catholic Medical Association.

PMID- 12199279
TI  - An excessive claim: sterilization and immediate material cooperation.

PMID- 12199281
TI  - The use of painkillers at the end of life.

PMID- 12199282
TI  - In vitro fertilization: truth and consequences.

PMID- 12199283
TI  - Social attitudes and the Human Genome Project: ethical implications.

PMID- 12199284
TI  - Abortion: correct application of natural law theory.

PMID- 12199285
TI  - Methotrexate and tubal pregnancies: direct or indirect abortion?

PMID- 12199286
TI  - The grand tradition: can it endure?

PMID- 12199287
TI  - Early induction of labor: legal and ethical considerations.

PMID- 12199288
TI  - Reflection on cloning: a document of the Pontificia Academia pro Vita.

PMID- 12199289
TI  - GeneNest: automated generation and visualization of gene indices.

PMID- 12199290
TI  - Institutional review boards not sufficiently monitoring recruitment of human
      subjects.

PMID- 12199291
TI  - Subject's parents say federal protection office had inherent conflict of
      interest.

PMID- 12199292
TI  - Institutional review boards and institutions not doing enough to protect human
      subjects.

PMID- 12199293
TI  - New steps for protecting human subjects by AAMC.

PMID- 12199294
TI  - Choice in prenatal testing.

PMID- 12199295
TI  - Do no harm.

PMID- 12199296
TI  - The stem cell debate.

PMID- 12199297
TI  - Disability community and identity: perceptions of prenatal screening.

PMID- 12199298
TI  - The thermic effect of food and obesity: discrepant results and methodological
      variations.
AB  - Studies have yielded discrepant results concerning whether the thermic effect of
      food (TEF) is reduced in obesity. Methodological variations among published
      studies make understanding the discrepant results very difficult. Although
      methodological differences are often noted as contributing to the discrepant
      results, little work has been done to address these differences and standardize
      experimental protocols. This paper reviews 50 studies that have investigated TEF
      in obesity and focuses on factors related to experimental protocol and subject
      control that reportedly affect measurements of resting energy expenditure,
      postprandial energy expenditure, and the calculation of TEF.

PMID- 12199299
TI  - Assessment of infant feeding: the validity of measuring milk intake.
AB  - Accurate assessment of infant feeding is needed for clinical practice and
      research. We identified 32 studies that evaluated the validity of direct
      observation, test weighing, or doubly labeled water methods. Correlations with
      validation standards were highest for doubly labeled water and test weighing, and
      lowest for observation. Cost and availability of isotope may limit the doubly
      labeled water method to research studies, whereas observation may be useful for
      clinical practice. Test weighing could be applied to either setting, but it may
      be practical to sample less frequently over 24 hours. Validity results and
      intended use of the measurement should be considered when selecting a method.

PMID- 12199300
TI  - Small amounts of dietary fructose dramatically increase hepatic glucose uptake
      through a novel mechanism of glucokinase activation.
AB  - Glucokinase plays a major role in the control of hepatic glucose uptake and
      storage as glycogen. Small amounts of fructose-1-phosphate, in the presence of
      relatively high glucose levels, markedly stimulate glucokinase through a novel
      mechanism of regulation involving dissociation from a regulatory protein and
      translocation from the nucleus into the cytosol. Using this understanding of
      glucokinase regulation, a recent study demonstrated that very small amounts of
      fructose (infused into the duodenum) could increase hepatic glucose uptake and
      glycogen storage, and reduce peripheral glycemia and insulin levels in the dog.
      These results suggest that very small amounts of dietary fructose could be
      beneficial in type 2 diabetes.

PMID- 12199301
TI  - Three vitamins are involved in regulation of the circadian rhythm.
AB  - Photoreceptors in the eyes of mammals synchronize the innate circadian rhythm to
      the solar light-dark cycle. They differ from the photoreceptors serving vision in
      rods and cones of the retina and are located in the ganglion cells of the retina.
      They consist of melanopsin, a protein homologous to rhodopsin, with retinal as
      the light-sensitive prosthetic group; and cryptochromes 1 and 2, proteins
      combined with methenyltetrahydrofolate and flavin adenine dinucleotide, which
      function as blue light-sensitive photoreceptors.

PMID- 12199302
TI  - From the farm to the kitchen table: the negative impact of antimicrobial use in
      animals on humans.
AB  - Antimicrobials used as growth promotion agents in the livestock and poultry
      industries appear to result in the spread of drug-resistant pathogens to humans
      such as vancomycin-resistant enterococci, fluoroquinolone-resistant Campylobacter
      jejuni, and multidrug-resistant strains of Salmonella enterica. We present some
      epidemiologic evidence supporting this link and suggest that the use of
      antimicrobial agents for nontherapeutic purposes in food animals should be
      severely limited, if not banned altogether.

PMID- 12199303
TI  - Dissociated backward priming effects in lexical decision and pronunciation tasks.
AB  - Backward priming was examined at 150- and 500-msec prime-target stimulus onset
      asynchronies (SOAs) using visually presented primes and targets in lexical
      decision and pronunciation tasks. Two kinds of backward relations were used:
      compound items for which targets and primes formed a word in the backward
      direction (e.g., prime: HOP; target: bell), and noncompound items for which
      targets and primes did not form a word but were associatively related in the
      backward but not the forward direction (e.g., prime: BABY; target: stork).
      Results showed that backward priming effects were equivalent for compounds and
      noncompounds. However, for lexical decisions, backward priming occurred at both
      SOAs, whereas for pronunciation, it occurred only at the 150-msec SOA. We discuss
      how this SOA-dissociated backward priming effect in lexical decision and
      pronunciation tasks poses a serious challenge for all theories of semantic
      priming.

PMID- 12199304
TI  - Fluent and nonfluent forms of transfer in reading: words and their message.
AB  - In two experiments, we examined transfer to the reading of a normal text from a
      prior reading of that intact text or from a prior reading of a scrambled word
      version of the passage. In Experiment 1, we studied good and poor readers in
      Grade 4; in Experiment 2, high- and low-ability undergraduate readers. Good
      readers at both ages showed rereading benefits only when the prior reading was of
      the intact text, with no reliable benefit from experience with words only. The
      poorer readers showed reliable rereading benefits even when only the words, in a
      scrambled order, were read on the first encounter. The results are discussed in
      terms of two forms of transfer nonfluent reading transfer when attention must be
      focused on word recognition, and fluent rereading transfer when word recognition
      is skilled so that attention can be focused on text processing.

PMID- 12199305
TI  - Remember-know judgments can depend on how memory is tested.
AB  - Remember-know judgments reflect the subjective state of awareness that
      accompanies episodic memory retrieval. We tested an old-new recognition
      condition, an old-new recognition followed by remember-know judgment condition,
      and a simultaneous remember-know-new judgment condition. These three conditions
      were tested for both a short (1-sec) and a long (4.5-sec) study duration.
      Reassuringly, results from the first two conditions did not differ from each
      other. Results from the third condition, however, differed from those in the
      first two conditions at both long and short study durations. Simultaneous
      consideration of all three alternatives resulted in a markedly liberal response
      bias, both in recognition detection and in the ascriptions of remember and know
      judgments. Discussion of the results is framed in terms of the single-process
      signal detection models that have been proposed to account for these subjective
      states of awareness.

PMID- 12199306
TI  - The item and list methods of directed forgetting: test differences and the role
      of demand characteristics.
AB  - In directed forgetting, the item method presents instructions to remember or to
      forget individual items; the list method presents a single mid-list instruction
      to forget the first half of the list. Initial free recall was better for remember
      (R) words than for forget (F) words under both methods. Offered 50 cents for each
      additional F word, subjects could recall almost no more items, eliminating a
      demand characteristics explanation. On a yes/no recognition test, only the item
      method showed directed forgetting. Retrospective instruction identification was
      good except for F words under the list method, where performance was at chance.
      There was no evidence of speed-accuracy tradeoff on the recognition or
      instruction identification tests. These results bring together the major findings
      concerning directed forgetting and support a method-based theoretical
      distinction.

PMID- 12199307
TI  - Source attributions and false memories: a test of the demand characteristics
      account.
AB  - When lists of related words are presented to subjects, they sometimes recall or
      recognize nonpresented words related to those lists (critical lures). In fact,
      subjects sometimes claim to remember which of two speakers said the critical
      lures. We examined whether this finding could be accounted for by demand
      characteristics. If subjects' willingness to make source attributions to critical
      lures reflects experimental demand, one would predict that subjects should be
      willing to change and should havelittle confidence in these attributions.
      Subjects made more attributions, were less likely to change their attributions,
      and were more confident in their attributions for critical lures than for
      unrelated distractors. Subjects had even more confidence in the attributions that
      they made for words that had actually been presented, and they were even less
      likely to change these attributions. These findings suggest that false memories
      are quite compelling but that they are also subtly different from true memories.

PMID- 12199308
TI  - Fictional narratives change beliefs: replications of Prentice, Gerrig, and Bailis
      (1997) with mixed corroboration.
AB  - We report three exact replications of experiments aimed at iluminating how
      fictional narratives influence beliefs (Prentice, Gerrig, & Bailis, 1997).
      Students read fictional stories that contained weak, unsupported assertions and
      which took place either at their home school or at an away school. Prentice et
      al. found that students were influenced to accept the assertions, even those
      blatantly false, but that this effect on beliefs was limited to the away-school
      setting. We questioned the limiting of the narrative effect to remote settings.
      Our studies consistently reproduced the first finding, heightened acceptance of
      statements occurring in the conversations of narrative protagonists, but we
      failed to reproduce the moderating effect of school location. In an attempt to
      understand these discrepancies, we measured likely moderating factors such as
      readers' need for cognition and their extent of scrutiny of the narratives.

PMID- 12199309
TI  - Synchrony effects in cognition: the costs and a benefit.
AB  - The present study investigated whether younger and older adults' ability to
      inhibit distractors in a problem-solving task is affected by synchrony, or the
      match between circadian arousal periods and time of testing. Consistent with an
      inhibitory-deficit explanation of synchrony effects, both age groups showed
      heightened susceptibility to distraction at off-peak relative to peak times. In
      most instances, increased sensitivity to distraction disrupted problem-solving
      performance; however, when distracting material was related to task goals,
      individuals actually benefited from reduced inhibitory efficiency. The present
      data are also consistent with other research in showing that access to and
      production of well-learned or familiar responses are not vulnerable to synchrony
      effects.

PMID- 12199310
TI  - Timeless demonstrations of Parkinson's first law.
AB  - "Work expands so as to fill the time available for its completion," Parkinson's
      law, is an explanation classic that has survived without an artifact-free
      demonstration at the individual level. To evaluate Parkinson's law, undergraduate
      subjects expected to judge four sets of photos of faces with reference to a
      subjective criterion. The experimental subjects, who were told that the fourth
      set was canceled before they began work on the third set, dallied on the third
      set; that is, as compared with controls, they prolonged work. The cancellation
      dalliance effect was reobtained in two exact replications. It was obtained again
      in a fourth study, a conceptual replication wherein subjects processed negatively
      toned phrases against an objective criterion. The generalizability of the effect
      and explanations for it are discussed.

PMID- 12199311
TI  - The ideal free distribution in humans: an experimental test.
AB  - How the distribution of resources affects the spatial distribution of animals is
      a central concern of behavioral ecology. One influential model relating
      population dynamics to individual foraging behavior is that of ideal free
      distribution (Fretwell & Lucas, 1970). This model assumes foragers of equal
      competitive abilities, moving freely from one habitat to another, the choices
      made by each individual subject are supposed to equalize gains across habitats.
      The resulting distribution at the group level, or ideal free distribution, has
      been tested with various animal species. Here we report an experimental test with
      human subjects competing for money. The results approximate those predicted by
      the ideal free model, the degree of approximation being consistent with that
      obtained in other species. This similarity of results supports the application of
      behavioral ecology models to humanperformance.

PMID- 12199312
TI  - Individual and developmental differences in working memory across the life span.
AB  - The effects of secondary tasks on verbal and spatial working memory were examined
      in multiple child, young adult, and older adult samples. Although memory span
      increased with age in the child samples and decreased with age in the adult
      samples, there was little evidence of systematic change in the magnitude of
      interference effects. Surprisingly, individuals who had larger memory spans when
      there was no secondary task showed greater interference effects than their age
      mates. These findings are inconsistent with the hypothesis that age and
      individual differences in working memory are due to differences in the ability to
      inhibit irrelevant information, at least as this hypothesis is currently
      formulated. Moreover, our results suggest that different mechanisms underlie
      developmental and individual differences in susceptibility to interference across
      the life span. A model is proposed in which memory span and processing speed both
      increase with development but are relatively independent abilities within age
      groups.

PMID- 12199313
TI  - An associative theory of estimating past dates and past prices.
AB  - The theory-a location theory, in W. J. Friedman's (1993) terminology-assumes that
      time information such as the date of an event is increasingly likely to become
      unavailable with passing time. The theory suggests that when people are asked to
      date events whose time is unknown, they find and supply time information for the
      most similar event and context for which it is available. Simulations of the
      dating process were compared with experimental results and produced similar
      patterns of error and bias. The theory is extended to explain errors and biases
      in how people estimate past prices.

PMID- 12199316
TI  - Restricted attentional capacity between sensory modalities.
AB  - The purpose of the experiments was to demonstrate an attentional-blink (AB)
      effect in a visual second task following the processing of a simple auditory
      signal. Subjects monitored a stream of letters presented at the middle of a
      computer screen using rapid serial visual presentation for the presence of a
      visual target (an X or a Y). In experimental trials, the visual target followed a
      pure tone that required an immediate speeded-choice response. When the tone had
      to be processed, accuracy in the visual-encoding task suffered a marked and
      prolonged deficit that was timelocked to the onset of the tone. When the tone
      could be ignored or when no tone was presented, no deficit was observed in the
      visual task. The results demonstrate a cross-modal AB effect produced by a simple
      two-choice auditory discrimination task. The results are consistent with the view
      that at least part of the AB effect has a central, amodal, postperceptual locus.

PMID- 12199315
TI  - Theoretical and empirical review of multinomial process tree modeling.
AB  - We review a current and popular class of cognitive models called multinomial
      processing tree (MPT) models. MPT models are simple, substantively motivated
      statistical models that can be applied to categorical data. They are useful as
      data-analysis tools for measuring underlying or latent cognitive capacities and
      as simple models for representing and testing competing psychological theories.
      We formally describe the cognitive structure and parametric properties of the
      class of MPT models and provide an inferential statistical analysis for the
      entire class. Following this, we provide a comprehensive review of over 80
      applications of MPT models to a variety of substantive areas in cognitive
      psychology, including various types of human memory, visual and auditory
      perception, and logical reasoning. We then address a number of theoretical issues
      relevant to the creation and evaluation of MPT models, including model
      development, model validity, discrete-state assumptions, statistical issues, and
      the relation between MPT models and other mathematical models. In the conclusion,
      we consider the current role of MPT models in psychological research and possible
      future directions.

PMID- 12199314
TI  - Deficits in lexical and semantic processing: implications for models of normal
      language.
AB  - The investigation of language processing following brain damage may be used to
      constrain models of normal language processing. We review the literature on
      semantic and lexical processing deficits, focusing on issues of representation of
      semantic knowledge and the mechanisms of lexical access. The results broadly
      support a componential organization of lexical knowledge-the semantic component
      is independent of phonological and orthographic form knowledge, and the latter
      are independent of each other. Furthermore, the results do not support the
      hypothesis that word meaning is organized into modality-specific subcomponents.
      We also discuss converging evidence from functional imaging studies in relation
      to neuropsychological results.

PMID- 12199318
TI  - What kind of attention modulates the Stroop effect?
AB  - An intersection of three literatures (skilled word recognition, spatial
      attention, and the Stroop effect) is addressed in a series of four experiments.
      The results, in conjunction with other observations, are taken to suggest that
      (1) the default value for spatial attention in visual word recognition is
      distributed across the word, (2) precuing a single letter position serves to
      narrow the focus of spatial attention, and (3) this reduces or prevents
      activation in the word recognition system. Consequently, the Stroop effect is
      reduced in magnitude or eliminated, depending on details of the context. Contrary
      to the widespread view that it reflects automatic processing, the Stroop effect
      is better conceptualized as reflecting the action of default settings in the word
      recognition and attentional systems. Some relations between consciousness,
      context, and control are noted.

PMID- 12199317
TI  - A salient distractor does not disrupt conjunction search.
AB  - Leading theories of attention posit that bottom-up and top-down factors
      simultaneously affect attentional priority in visual search. Recent evidence,
      however, suggests that subjects may rely exclusively on top-down guidance when
      searching for a target defined by a specific known feature (Bacon & Egeth, 1994).
      In the present experiment, we addressed this issue in a conjunction search task.
      We investigated how searching for a green O among green Ts and red Os is affected
      by the presence of a distractor with a unique shape (green X), color (blue O), or
      both (blue X). We showed that the salient distractor does not disrupt performance
      on target-present trials, but produces a large interference on target-absent
      trials. We conclude that salience-based and top-down processes are alternative
      modes of guidance, rather than joint contributors in the allocation of
      attentional priority.

PMID- 12199320
TI  - Ki-67 antigen detection in unstained and destained cytologic samples.
AB  - OBJECTIVE: To evaluate the effect of different tissue preservation, fixation and
      staining procedures on the expression of proliferation-associated Ki-67 antigen
      in cytologic samples to establish an easy and uniform way to handle cytologic
      specimens with an automated staining technique. STUDY DESIGN: Multiple touch
      imprints were made from eight breast tumors. The specimens were treated according
      to different protocols, and Ki-67 nuclear expression was compared to that in the
      corresponding histologic sections. RESULTS: In the unstained specimens, air
      drying at room temperature for up to four months or ethanol spray fixation
      preserved the material and offered excellent results. Processing effectively
      removed previous stain without additional chemical destaining. Antigen retrieval
      was not achieved in the previously Giemsa stained imprints and was suboptimal in
      those stained according to Papanicolaou. CONCLUSION: Immunocytochemical detection
      of Ki-67 is recommended for previously unstained cytologic specimens.

PMID- 12199319
TI  - Statistical analysis of chemopreventive efficacy of vitamin A in sun-exposed,
      normal skin.
AB  - OBJECTIVE: To develop numeric, statistically secured measures of chemopreventive
      efficacy and to derive procedures with high sensitivity of detection. STUDY
      DESIGN: Karyometric features were computed for nuclei from the basal cell layer
      of biopsies taken from sun-exposed but histologically "normal" skin. Biopsies
      were collected from placebo-treated subjects and subjects treated for one year
      with daily, oral doses of 25,000, 50,000 and 75,000 IU of vitamin A. A total of
      22,600 nuclei were recorded from 113 cases, at baseline and after one year.
      RESULTS: Two numeric measures of chemopreventive efficacy were applied: a measure
      of nuclear abnormality and a measure based on discriminant function scores. Both
      showed statistically significant chemopreventive effects of vitamin A. Dose
      response curves were derived. A novel procedure, second order discriminant
      analysis, resulted in very high sensitivity for the detection of change in
      nuclear chromatin patterns. CONCLUSION: Karyometric analysis has increased in
      sensitivity such that changes on the order of 10%, found in only a low percentage
      of nuclei in a biopsy specimen, can be reliably documented. The methodology lends
      itself to cost-efficient screening of compounds for chemopreventive efficacy.

PMID- 12199322
TI  - Value of image cytometry in the subclassification of rhabdomyosarcoma.
AB  - OBJECTIVE: To test the discriminatory capability of nuclear features in the
      subclassification of rhabdomyosarcoma (RMS) and especially to differentiate
      embryonal from alveolar RMS. STUDY DESIGN: The study included 42 patients with
      RMS. We performed the analysis on Feulgen-stained filtrates of cell suspensions
      prepared from deparaffinized tissue sections. Image analysis was performed by an
      automated, high-resolution image cytometer on at least 200 nuclear images.
      Photometric, morphometric and nuclear texture features were analyzed. Probability
      density distributions were calculated for each nuclear feature of individual RMS
      subgroups and compared in order to detect possible differences. RESULTS: There
      were significant differences between embryonal and alveolar RMS in five nuclear
      features: DNA index, sphericity, elongation, low_DNA_area and fractall_area. We
      were able to differentiate between the two main RMS subgroups in 82% of cases on
      the basis of either sphericity or elongation alone, while the power of
      differentiation for texture features was 72-79%. CONCLUSION: Differentiation
      between embryonal and alveolar RMS using one nuclear feature is not an important
      adjunct to light microscopy. However, the possibility of using a combination of
      nuclear features would probably increase the discriminatory ability.

PMID- 12199321
TI  - Ki-67 and AgNOR proliferative markers as diagnostic adjuncts to fine needle
      aspiration cytology of thyroid follicular lesions.
AB  - OBJECTIVE: To differentiate hyperplastic nodules (HPN), follicular adenoma (FA)
      and follicular carcinoma (FCA) of the thyroid by cytomorphologic features
      combined with argyrophilic nucleolar organizer regions (AgNORs) and Ki-67
      proliferative markers on fine needle aspiration cytology. STUDY DESIGN:
      Cytomorphologic patterns, along with two proliferation markers, Ki-67 and AgNORs,
      in fine needle aspirates of 123 histologically confirmed cases of thyroid
      follicular lesions, including 39 hyperplastic nodules, 70 follicular adenomas and
      14 cases of follicular carcinomas, were recorded. RESULTS: Mean AgNOR (mAgNOR)
      counts and Ki-67 labelling index (LI) were consistently higher in FCA in
      comparison to FA and HPN irrespective of the cytologic patterns in fine needle
      aspiration smears. Between benign and malignant lesions, an overlap of 1.83% at
      the cutoff point of 4.0 was observed in cases of mAgNORs, whereas it was 11.09%
      at a cutoff of 5.0 in cases of Ki-67 LI. CONCLUSION: mAgNOR counting in fine
      needle aspiration smears is more sensitive, simple and cost effective as compared
      to Ki-67 LI for differentiating between benign and malignant thyroid follicular
      neoplasms.

PMID- 12199323
TI  - Gonadotropin-releasing hormone receptors in prostate tissue.
AB  - OBJECTIVE: To perform an immunohistochemical analysis of gonadotropin-releasing
      hormone receptors (GnRH-Rs) in archival prostate tissue. STUDY DESIGN: Thirteen
      benign prostatic hyperplasia (BPH) specimens from open surgery, 48 radical
      prostatectomy specimens (30 surgery only and 18 neoadjuvant hormone treatment and
      surgery) and 14 prostate needle biopsies were examined. The avidin-biotin
      peroxidase technique and monoclonal antibody A9E4 against the extracellular
      domain of GnRH-Rs were employed. Cases with > 5% immunoreactive cells (IR) were
      considered positive. RESULTS: The epitheliumfrom all 13 cases of BPH was
      immunoreactive. Most tumor cellsfrom biopsies were IR positive. Twenty-seven of
      30 surgery-only specimens were IR positive vs. 8/18 in the surgery and
      neoadjuvant hormone treatment group. CONCLUSION: GnRH-Rs have been
      histochemically demonstrated in normal lutenizing hormone/follicle-stimulating
      hormone pituitary cells. In cell lines LN-CaP and DU-145, Gn-RH-R was identical
      to that of the pituitary. GnRH-Rs in the prostate can be quite easily assessed
      immunohistochemically in archival tissue samples, and hormone treatment
      significantly decreases the immunoreactivity of GnRH-Rs in prostate cancer
      tissue. This strongly suggests that GnRH agonists bind to BPH and prostate cancer
      cells.

PMID- 12199324
TI  - Angiogenesis as an independent prognostic indicator in node-negative breast
      cancer.
AB  - OBJECTIVE: To quantitate tumor angiogenesis in carcinoma of the breast (stage
      T2N0M0) by computerized image analysis of CD-31-stained histologic sections and,
      keeping in view the heterogeneity of tumors, to assess which areas of
      neovascularization provide the best prognostic indicator. STUDY DESIGN: Thirty
      six cases of infiltrating duct carcinoma of the breast, stage T2N0M0, with follow
      up of five years, were analyzed. All cases had received uniform initial treatment
      in the form of mastectomy with axillary clearance and radiotherapy. Intratumoral
      microvessel density (IMD) counts were done on "hot spots" and "non-hot spots" on
      CD-31-stained sections using computerized image analysis. Angiogenesis was
      correlated with other variables, such as age, menopausal status, histologic grade
      and proliferative activity by univariate and multivariate analyses. RESULTS: Hot
      spot IMD counts were highly significant independent prognostic markers in
      univariate and multivariate analyses. Background vascularity of a tumor was of no
      value in prognosticating. CONCLUSION: In patients with node negative breast
      carcinoma, IMD counts in hot spots are an independent prognostic factor in
      disease-free and overall survival and can be used to separate out patients with
      T2N0M0 stage in need of systemic adjuvant therapy.

PMID- 12199325
TI  - Differentiating benign nevi from malignant melanoma using DNA microdensitometry
      and karyometry and maturation: a zonal comparison, correlation and multivariate
      analysis.
AB  - OBJECTIVE: To evaluate the diagnostic effectiveness of cytometric features of DNA
      microdensitometry, karyometry (nuclear morphometry) and maturation and their
      combinations in separating benign nevi from malignant melanomas. STUDY DESIGN:
      Tumor cells were measured from each of the superficial, middle and deep zones of
      81 melanocytic lesions using video image analysis for nuclear DNA content,
      chromatin compactness, and nuclear size and shape variables. There were 27 banal
      compound melanocytic nevi, 20 dysplastic compound nevi, 10 Spitz nevi and 24
      malignant melanomas (MM). Maturation of cells with depth into the dermis was also
      studied by comparing cells from superficial to deep zones. RESULTS: MM showed
      distinct characteristics of DNA microdensitometry, karyometry and maturation as
      compared to all groups of benign nevi. There were overall close correlations
      between nuclear DNA content variables and nuclear size parameters in the total
      group of 81 lesions. However, there were fewer significant correlations between
      the various indices in the group of melanomas alone. Using multivariate
      discriminant analysis, up to 97% of the lesions could be correctly separated as
      benign or malignant by a combination of five key microdensitometric, karyometric
      and maturation parameters. CONCLUSION: DNA microdensitometry, karyometry and
      maturation parameters have independent abilities in identifying individual
      malignant melanomas. Coevaluation of various cytometric features and maturation
      profiles offers better diagnostic ability in separating benign nevi from MM.

PMID- 12199326
TI  - Clinical predictors of mucormycosis in children with type 1 diabetes mellitus.
AB  - BACKGROUND: Mucormycosis is an acute, often rapidly fatal fungal infection that
      is an important cause of death in young patients with diabetes mellitus (DM) who
      have poor glycemic control and acute ketosis. Despite the importance of this
      condition, the clinical predictors of mucor infection are not well defined.
      METHODS: A retrospective chart review was carried out for five patients, age 14
      19 years, diagnosed with mucormycosis at the University of Florida between 1984
      and 1999. For the three patients for whom adequate information was available, two
      randomly selected, age-matched case controls were selected and compared to
      affected patients for the following variables: average HbA1c concentrations,
      number of missed clinic appointments, and the number of hospital and Diabetes
      Project Unit (DPU) admissions. RESULTS: HbA1c levels were similar in affected
      patients and controls, indicating glycemic control is not the principal factor
      predisposing to mucor infection. African-American race and poor compliance, as
      evidenced by poor clinic attendance, risk-taking behaviors and high admission
      rate to the DPU, were predictors of increased susceptibility to infection with
      mucormycosis.

PMID- 12199327
TI  - Continuous subcutaneous insulin infusion in the treatment of children and
      adolescents with type 1 diabetes mellitus.
AB  - Continuous subcutaneous insulin infusion (CSII) with a portable insulin pump has
      been used for several years in the treatment of adult patients with diabetes
      mellitus (DM). This treatment, however, has rarely been utilised in children and
      adolescents. We studied the use of CSII in 16 children and adolescents with type
      1 DM at Tampere and Kuopio University Hospitals between 1992 and 1997. The
      longest treatment periods are more than 4 years. The reasons for switching to
      CSII treatment and the goals achieved were evaluated. Glycaemic control before
      and during CSII treatment and the occurrence of hypoglycaemia and ketoacidosis
      were analysed. Compared with conventional insulin treatment, improved glycaemic
      control and a reduced frequency of hypoglycaemic events were achieved with CSII
      in those with particularly poor initial metabolic control (HbA1c >10.0%). The
      overall satisfaction with pump therapy was high in both patients and their
      families. According to our experience, CSII may be of benefit, especially in
      young infants with type 1 DM, but also in affected adolescents with unacceptable
      glycaemic control.

PMID- 12199328
TI  - Obesity and lipid profiles in children and adolescents.
AB  - Childhood obesity is associated with unfavorable lipid profile, suggesting that
      obese children should be screened for hypercholesterolemia. However, the
      prevalence of hypercholesterolemia in childhood obesity, and the effect of the
      degree of obesity on lipid profile, are unknown. Eighty-nine obese children and
      adolescents (BMI >85%, mean age 10.4 +/- 2.5 years) and 53 non-obese control
      children matched for age, gender and pubertal stage participated in the study.
      Early morning blood samples for serum lipids were collected in all children after
      a 12-h fast. Mean serum cholesterol and triglycerides (TG) levels were
      significantly higher (p <0.05) among the obese children (cholesterol: 175.2 +/-
      31.4 vs 143.3 +/- 24.3 mg/dl; TG: 122.8 +/- 69.7 vs 94.3 +/- 37.8 mg/dl in obese
      and control children, respectively). Among the obese children, 52% had elevated
      serum cholesterol levels (>170 mg/dl) compared to 16% in the controls. The degree
      of obesity (BMI 85-95% vs BMI >95%) had no effect on serum lipids. Unfavorable
      lipid levels were relatively common among obese children, suggesting that obesity
      should be considered a risk factor for hypercholesterolemia, and that screening
      obese children for hypercholesterolemia should be considered.

PMID- 12199329
TI  - Adolescent rickets in Saudi Arabia: a rich and sunny country.
AB  - In this retrospective study from Saudi Arabia, which is a rich and sunny country,
      we report our experience with 34 adolescents (20 females, 10 males) with rickets.
      The commonest cause was vitamin D deficiency (58.8%) followed by rickets due to
      low calcium intake (11.8%) and genetic causes, including possible 25-hydroxylase
      deficiency (8.8%). The etiology of nutritional rickets is multifactorial,
      including lack of sun exposure and inadequate calcium intake. The clinical
      symptoms were nonspecific and therefore cases in this country are either
      underdiagnosed or missed. Vitamin D deficient patients needed an average of 19
      months of treatment before recovery. High dose vitamin D plus calcium
      supplementation are recommended for treatment. Measures to prevent rickets in all
      age groups including adolescents are suggested. Further studies on nutritional
      and genetic forms of rickets are recommended.

PMID- 12199330
TI  - Iodine and selenium deficiency in school-children in an endemic goiter area in
      Turkey.
AB  - Endemic goiter is one of the most important health problems in Turkey. However,
      there are not enough studies associated with iodine and selenium status. This
      study was carried out to establish the effects of iodine and selenium levels on
      thyroid gland size and thyroid functions in 73 healthy school-children, 7-12
      years old (mean 9.56 +/- 1.77 years), 38 girls (52%) and 35 boys (48%), living in
      an endemic goiter area. Goiter was found in 32 of the children (43.8%) by
      palpation, and 56 of the children (76.7%) by ultrasonography. Mean serum T3 and
      TSH levels were in the upper limit of normal, and mean serum T4 levels were
      within the normal limits, but mean serum thyroglobulin levels were higher than
      the normal limits. Mean serum selenium level was 30.84 +/- 23.04 microg/l, and
      mean urinary iodine level was 3.91 +/- 3.77 microg/dl, appropriate for moderate
      iodine and selenium deficiency. Thyroid volumes of the children were negatively
      correlated with serum selenium levels, but there was no correlation with urinary
      iodine levels and thyroid hormones. In conclusion, school-children in this area
      had significant goiter problems, probably due to the iodine and selenium
      deficiencies.

PMID- 12199331
TI  - No seasonality of birth in children with type 1 diabetes mellitus in Ankara,
      Turkey.

PMID- 12199332
TI  - Growth retardation in children with IgA deficiency.
AB  - We evaluated the clinical and immunological manifestations of 14 children with
      IgA deficiency. Four of the patients were asymptomatic, and ten were symptomatic,
      with recurrent sinopulmonary infections, allergic disease, recurrent intestinal
      giardiasis or celiac disease. Growth retardation was the second important feature
      in our patients. One of the seven patients with growth retardation had partial
      growth hormone deficiency. The levels of serum IgG and IgM were high in five and
      three patients, respectively. Cellular immunity was normal.

PMID- 12199333
TI  - Intronic mutation in the growth hormone receptor gene in a Peruvian girl with
      Laron syndrome.

PMID- 12199334
TI  - Novel mutation involving the translation initiation codon of the growth hormone
      receptor gene (GHR) in a patient with Laron syndrome.
AB  - Laron syndrome (LS) or growth hormone (GH) insensitivity syndrome (GHIS) is an
      autosomal recessive disease due to molecular defects in the GH receptor gene
      (GHR). Most of the identified mutations are located on the extracelular domain of
      the receptor. We studied the GHR gene in a patient with LS and found a homozygous
      missense mutation in exon 2. The novel mutation is an A-->T transversion (ATG -
      >TTG) that abolishes the translation initiation codon of the GHR gene. This
      mutation is expected to prevent the translation of the protein. We present
      clinical, biochemical and molecular evidence of Laron syndrome as the result of a
      mutation (ATG-->TTG) in the codon for the initial methionine of the GHR gene.

PMID- 12199335
TI  - Molecular analysis of Frasier syndrome: mutation in the WT1 gene in a girl with
      gonadal dysgenesis and nephronophthisis.
AB  - The Wilms' tumor gene (WT1) encodes a protein that is believed to exert
      transcriptional and tumor-suppressor activities. Mutations in this gene have
      occasionally been associated with Wilms' tumor (<15% patients) and, more
      consistently, with three syndromes characterized by urogenital abnormalities
      (WAGR, Denys-Drash and Frasier syndromes). We report 17 years follow-up of a 29
      year-old phenotypic female with 46,XY karyotype, gonadal dysgenesis and
      nephronophthisis in order to identify possible germline alterations of the WT1
      gene. Frasier syndrome was suspected and confirmed by genetic analysis. Sequence
      analysis permitted the identification of an A40-->G mutation in position +5 in
      the donor splice site of intron 9. During surgery for streak gonads extirpation,
      a microscopic gonadoblastoma was found, a typical complication of Frasier
      syndrome.

PMID- 12199336
TI  - Growth and ovarian function in girls with 48,XXXX karyotype--patient report and
      review of the literature.
AB  - The loss of an X chromosome results in short stature and often in primary ovarian
      failure, but the effect of extra X chromosomes is less clear, especially in
      48,XXXX women. We report a girl with a 48,XXXX karyotype with tall stature (181.8
      cm), primary ovarian failure and low DHEAS levels. A review of the literature
      shows that, apart from an intellectual deficit, the phenotype is very
      heterogeneous. The few data that are available in the literature indicate that
      tall stature and primary ovarian failure are not essential characteristics of the
      48,XXXX phenotype.

PMID- 12199337
TI  - Cirrhotic outcome in patients with craniopharyngioma.

PMID- 12199338
TI  - Amative orientation: the hormonal hypothesis examined.
AB  - The hypothesis that human male and female amative orientation, arousal and
      courtship are sex-hormone dependent had as its precursor John Hunter's recorded
      but unpublished 18th century experiments of cross-sexed gonadal transplants in
      chicks. The hypothesis gained momentum in the 20th century after the discovery
      and eventual marketing of the sex hormones, and after the experimental
      demonstration by William C. Young that, in guinea-pigs, cross-sexed hormone
      administered prenatally influenced their subsequent male/female courtship and
      mating behavior. Comparatively and in review, human clinical syndromes of
      hypermasculinization and hypomasculinization do not disconfirm the hormonal
      hypothesis, but they do not adequately confirm it, either. They are compatible
      with the idea of a cofactor that governs whether amative orientation in practice,
      ideation and imagery is homosexual, heterosexual or bisexual.

PMID- 12199339
TI  - When should we measure growth hormone binding protein?

PMID- 12199340
TI  - Serum leptin and leptin binding activity in children and adolescents with
      hypothalamic dysfunction.
AB  - Marked disturbance in eating behaviour and obesity are common sequelae of
      hypothalamic damage. To investigate whether these were associated with
      dysfunctional leptin central feedback, we evaluated serum leptin and leptin
      binding activity in 37 patients (age 3.5-21 yr) with tumour or trauma involving
      the hypothalamic-pituitary axis compared with 138 healthy children (age 5.0-18.2
      yr). Patients were subdivided by BMI <2 SDS or > or = 2 SDS and healthy children
      and children with simple obesity of comparable age and pubertal status served as
      controls. Patients had higher BMI (mean 1.9 vs 0.2 SDS; p <0.001), a greater
      proportion had BMI > or = 2 SDS (54% vs 8%; p <0.001) and higher serum leptin
      (mean 2.1 vs 0.04 SDS; p <0.001) than healthy children. Serum leptin (mean 1.1 vs
      -0.1 SDS; p = 0.004) and values adjusted for BMI (median 0.42 vs 0.23
      microg/l:kg/m2; p = 0.02) were higher in patients with BMI <2 SDS. However, serum
      leptin adjusted for BMI was similar in patients with BMI > or = 2 SDS compared to
      corresponding controls (1.08 vs 0.95; p = 0.6). Log serum leptin correlated with
      BMI SDS in all subject groups but the relationship in patients with BMI <2 SDS
      was of higher magnitude (r = 0.65, slope = 0.29, p =0.05 for difference between
      slopes) than in healthy controls (r = 0.42, slope = 0.19). Serum leptin binding
      activity (median 7.5 vs 9.3%; p = 0.02) and values adjusted for BMI (median 0.28
      vs 0.48 % x m2/kg; p <0.001) were lower in patients than in healthy children. The
      markedly elevated leptin levels with increasing BMI in non-obese patients with
      hypothalamic-pituitary damage are suggestive of an unrestrained pattern of leptin
      secretion. This along with low leptin binding activity and hence higher free
      leptin levels would be consistent with central leptin insensitivity.

PMID- 12199341
TI  - Linear growth in children with congenital hypothyroidism detected by neonatal
      screening and treated early: a longitudinal study.
AB  - We performed a longitudinal study of a cohort of 74 children with congenital
      hypothyroidism (CH) detected by neonatal screening (Buenos Aires Province,
      Argentina) up to the age of 3 years old, in order to study linear growth and the
      relationship with the severity of CH at diagnosis. The mean age at diagnosis and
      the start of the treatment was 16.9 +/- 5.2 days. The patients were divided into
      group 1--severe CH (pretreatment T4 level <4 microg/dl) (n = 47)--and group 2-
      less severe CH (pretreatment T4 level > or = 4 microg/dl) (n = 27). Patients with
      CH treated early showed a sexually dimorphic pattern of growth: girls tended to
      be longer than boys at all ages. Boys showed some delay of growth during the
      first year. No difference was found in linear growth between the two groups
      (more/less severe CH). Height was normal in both sexes at the age of 3 years old.

PMID- 12199342
TI  - Systematic ultrasound screening as a significant tool for early detection of
      thyroid carcinoma in Belarus.
AB  - We report the results of ultrasound screening of the thyroid gland in 3,051
      Belarus children 4-14 years of age exposed to radioactive fallout due to the
      Chernobyl accident. Screening was performed in 1990, 1993 and 1998. The study
      demonstrated that with time the prevalence of thyroid nodules in this
      contaminated region increased from 1.2% to 3.5%, mostly due to pathologically
      verified nodular goiter and non-verified small solid nodules and cysts. In
      contrast, the prevalence of thyroid carcinoma decreased from 0.6% in 1990 to 0.3%
      in 1993. We found 15 patients with carcinoma. On analysis of the ultrasound
      pattern of all carcinomas, we observed nodular and diffuse variants. Thus, we can
      conclude that systematic ultrasound screening is useful for the early detection
      of thyroid carcinoma in the population of Belarus exposed to radiation due to the
      Chernobyl accident.

PMID- 12199343
TI  - Decreased cortisol secretion in nonclassical 21-hydroxylase deficiency before and
      during glucocorticoid therapy.
AB  - OBJECTIVE: The cortisol response in patients with nonclassical 21-hydroxylase
      deficiency (NC21OHD) was assessed before and during hydrocortisone therapy and
      the findings were related to genotype. DESIGN: Comparative study. METHODS: The
      study sample comprised 41 patients (10 males) with NC21OHD, divided into two
      groups according to the genetic analysis of the CYP21 gene: Group A carried two
      mild mutations (n = 29), and Group B were compound heterozygotes for one mild and
      one severe mutation (n = 12). The 250 microg short ACTH test was performed at
      diagnosis. To evaluate the degree of treatment-induced suppression of adrenal
      function, 31 patients also underwent the 1 microg/1.73 m2 ACTH test during
      hydrocortisone therapy. Basal and stimulated cortisol levels and the increment in
      cortisol response were compared between Groups A and B and between the whole
      patient sample and healthy controls (32 subjects for the 250 microg test and 29
      for the 1 microg/1.73 m2 test). RESULTS: The basal, stimulated, and incremental
      cortisol levels were similar in Groups A and B; therefore, all the patients were
      considered together. At diagnosis, the basal cortisol levels were similar in the
      patients and controls, but the stimulated and incremental cortisol levels were
      significantly lower in the patients (p <0.001 for both). During hydrocortisone
      therapy, the patients had slightly higher basal cortisol levels than the controls
      (p = 0.04), but significantly lower stimulated and incremental cortisol levels (p
      <0.001 for both). CONCLUSIONS: Cortisol levels in NC21OHD are similar in patients
      carrying two mild mutations and in compound heterozygotes for one mild and one
      severe mutation. Stimulated and incremental cortisol levels in response to the
      short ACTH test might be decreased not only during but also before hydrocortisone
      therapy. Therefore, coverage with a stress dose of hydrocortisone during serious
      intercurrent illness or surgery is recommended in patients with NC21OHD,
      especially those previously treated with corticosteroids.

PMID- 12199345
TI  - McCune-Albright syndrome: molecular genetics.
AB  - McCune-Albright syndrome (MAS) is a rare disorder characterized by the
      association of precocious puberty (mostly in girls), polyostotic fibrous
      dysplasia and cafe-au-lait pigmented skin lesions. In addition to this classical
      triad, several endocrine disorders, all due to autonomous hormonal
      hyperproduction, can also be associated, such as pituitary adenomas secreting
      growth hormone, hyperthyroid goiters, or adrenal hyperplasia. The distribution
      pattern of skin lesions and the sporadic character of MAS have led to the
      hypothesis that this syndrome is due to a dominant somatic mutation early in the
      course of development. Furthermore, the diverse endocrine hyperactivity syndromes
      observed in MAS have in common the involvement of cells that respond to
      extracellular signaling by activating the adenyl cyclase system. The
      identification of somatic mutations of the Gsalpha gene have shown that MAS is
      due to a post-zygotic activating mutation of the Gsalpha subunit leading to a
      mosaic distribution of cells bearing constitutively active adenyl cyclase
      activity. In all patients reported to date, the mutation is a substitution of the
      arginine residue at position 201 most often into histidine or cysteine. We
      present here some of the results we have obtained in studying 80 patients
      presenting one or several signs of MCA for identification of the Arg201 mutation.
      We used a PCR-based method that allows selective enrichment of mutated DNA. This
      study, and data in the literature during the last decade, has widened the
      definition of MAS. Affections as clinically different as somatotropic or
      thyrotropic adenomas, isolated polyostotic fibrous dysplasia, isolated peripheral
      precocious puberty and the classic McCune-Albright syndrome all appear to be
      elements of a wide spectrum of disease based on the same molecular defect. The
      developmental moment at which the mutation occurs determines both the number of
      tissues affected and the severity of expression. The application of tools from
      molecular genetics to the study of this syndrome confirms their essential
      contribution to a deeper understanding of endocrine pathologies.

PMID- 12199344
TI  - ABCC8 (SUR1) and KCNJ11 (KIR6.2) mutations in persistent hyperinsulinemic
      hypoglycemia of infancy and evaluation of different therapeutic measures.
AB  - Persistent hyperinsulinemic hypoglycemia of infancy (PHHI) can occur as a result
      of mutations in the subunits that form the ATP-sensitive potassium channel
      (K+ATP) in pancreatic beta-cells which play a major role in modulating insulin
      secretion from the beta-cells. Mutations have been shown in the genes for these
      subunits, namely for the plasma membrane sulfonylurea receptor (SUR1), ABCC8, and
      its associated inwardly rectifying potassium channel (KIR6.2) KCNJ11. Drugs which
      act on K+ATP channels, such as diazoxide, seem to need intact ABCC8 to be able to
      show their effects. Thus, it would be desirable to know the exact locus of the
      abnormality in the beta-cell to be able to choose the right therapeutic agent or
      to perform early pancreatectomy. The aim of this study was to search for the
      correlation between the mutations of the K+ATP channel and the outcome of
      therapeutic measures in patients with PHHI followed for a duration of 4 months to
      7.3 years. Thirteen patients (5 F, 8 M) with PHHI with a median age of 2.5 months
      (8 days-12.1 years) were included in the study. Therapy for PHHI was initiated
      either with diazoxide (n = 9) or with calcium channel blocker (n = 4) as the
      agent of first choice. Three patients unresponsive to drugs underwent 95%
      pancreatectomy. Mutation analysis was performed by polymerase chain reaction
      (PCR) and single strand conformation polymorphism (SSCP) in DNA samples extracted
      from patients' peripheral leukocytes. The PCR products were directly sequenced.
      Screening of ABCC8 and KCNJ11 for mutations revealed abnormalities in the ABCC8
      gene in three patients out of 13: homozygosity for the 155del1 mutation, compound
      heterozygosity for T267-->G/A4612-2-->G, and compound heterozygosity for G4310-
      >A/ R1494Q. No mutations in the KCNJ11 gene were identified. Of the three
      patients who underwent pancreatectomy, two had identified mutations and one did
      not have any known mutation. In two patients in whom hyperinsulinism recurred
      after surgery and in the rest of the children, therapy with either diazoxide or
      calcium channel blocker proved to be effective in controlling hypoglycemia over
      the follow-up period. Thus it may be concluded that mutations in the ABCC8 gene
      were not predictive of the response to drugs. Unidentified mutations in the K+ATP
      channels other than those screened or other functional abnormalities in these
      channels may account for the different therapeutic responses.

PMID- 12199346
TI  - Searching for Arg201 mutations in the GNAS1 gene in Italian patients with McCune
      Albright syndrome.
AB  - McCune-Albright syndrome (MAS) is a rare disease caused by somatic postzygotic
      mutations at Arg201 in the GNAS1 gene that encodes for the Gsalpha protein.
      Arg201 mutations are gain-of-function mutations in affected tissues (including
      bone, skin, endocrine glands and other tissues) that result in the activation of
      cAMP. We used a polymerase chain reaction(PCR)-based technique for the selective
      enrichment and analysis of the Arg201 mutant allele in 27 different tissues from
      24 Italian patients with one or more signs of MAS. Arg201 mutations were
      identified in 13 different tissues (48.1%) from 11 patients (45.8%). Mutation
      detection rates differed across the various types of tissue samples, and the
      mutation was not always found in every tissue sample from the same patient. To
      overcome problems in the analysis of mutations in somatic mosaicism, as occurs in
      MAS, a highly sensitive molecular technique should be applied, the most
      appropriate tissue source selected, and various affected tissues from the same
      patient analyzed.

PMID- 12199347
TI  - Premature thelarche and granulosa cell tumors: a search for FSH receptor and
      G5alpha activating mutations.
AB  - Activating mutations of the Gsalpha gene are responsible for McCune-Albright
      syndrome and have also been identified in sporadic tumors of the pituitary and
      thyroid. When associated with malignancy, activating Gsalpha mutations are known
      as gsp-oncogenes. We hypothesized that similar activating mutations might also
      account for some cases of premature thelarche and/ or granulosa cell tumors.
      Polymerase chain reaction and DNA sequencing was used to screen for activating
      mutations of Gsalpha genes in children with premature thelarche and in pathologic
      specimens from juvenile and adult granulosa cell tumors. Because these disorders
      involve over-activity of the FSH-signaling pathway, we also screened for
      activating mutations of the FSH receptor. No mutations were detected in either
      the Gsalpha or the FSHR fragment studied. Previously reported polymorphisms
      (Ser680Asn and Ala307Thr) of the FSHR were detected in 25/27 tumor samples and
      9/9 premature thelarche samples. We conclude that activating mutations in
      previously identified mutation 'hot-spots' in the Gsalpha and FSH receptor genes
      are probably not a major cause of premature thelarche or granulosa cell tumors.
      In contrast, polymorphisms of the FSH receptor are common.

PMID- 12199348
TI  - McCune-Albright syndrome--the German experience.
AB  - The classical McCune-Albright syndrome (MAS) consists of peripheral precocious
      puberty (PPP), fibrous bone dysplasia and cafe-au-lait spots. We conducted a
      survey among pediatric endocrinologists in Germany, Austria and Switzerland, most
      of them participating in the German Working Group for Pediatric Endocrinology
      (APE). Thirty-three physicians reported 58 patients. A detailed questionnaire
      yielded extensive data from 41 patients. Patients (36 females, 5 males) were
      diagnosed between the 4th week of life and 8 years. Symptoms included precocious
      puberty (37 patients), cafe-au-lait spots (35), fibrous bone dysplasia (32),
      hyperthyroidism (5), liver disease (5), phosphate wasting (4), GH hypersecretion
      (3), anemia in infancy (2), hyperprolactinemia (1), and Cushing's disease (1).
      Therapy of PPP included testolactone (15), tamoxifen (7), cyproterone acetate
      (CPA) (5), anastrozole (1) and exemestane (1). Testolactone, tamoxifen and CPA
      showed varying degrees of clinical remission; none was unanimously effective, but
      side effects were very rare. New aromatase inhibitors were not well validated in
      MAS. Eleven children received bisphosphonate therapy (pamidronate i.v. q 3
      months) for fibrous bone dysplasia. Pamidronate was well tolerated, and pain
      improved when present, but data on preventive effects are not yet available. In
      conclusion, this survey describes a large cohort of patients with MAS, many with
      severe clinical problems, including major physical handicaps. Our results show
      that there is no 'gold standard' for the therapy of PPP; tested treatment
      regimens are not ideal, and new aromatase inhibitors need to be evaluated in
      controlled studies. Pamidronate was well tolerated, but preventive effects on
      bone dysplasia have not yet been proven.

PMID- 12199349
TI  - Ovarian function in three female patients with McCune-Albright syndrome with
      persistent autonomous ovarian activity.
AB  - Autonomous ovarian activity persists throughout adolescence in some patients with
      McCune-Albright syndrome (MAS). There have been few studies of longitudinal
      assessment of ovarian function in these patients. We investigated the first
      morning voided urinary gonadotropin and ovarian steroid levels consecutively in
      three patients aged 3 to 7 years after withdrawal of therapy for precocious
      puberty. They had the triad of MAS with onset of menses within the first 3 years
      of life. Excessively elevated urinary estrogen levels with one or two peaks per
      cycle were found in all patients. In two patients, cafe-au-lait spots and
      dysplastic bones were located unilaterally. These two patients showed
      significantly increased urinary pregnanediol levels, suggesting ovulation, with
      low levels of gonadotropins in one patient and moderately low levels with an LH
      surge in the other. Thus, only a unilateral ovary was anticipated to be mutated
      with persistent autonomous ovarian activity. In the remaining patient with
      bilateral involvement of tissues, relatively high LH and low FSH levels
      throughout a cycle were found with no rise in urinary pregnanediol.

PMID- 12199350
TI  - Impact of endocrine hyperfunction and phosphate wasting on bone in McCune
      Albright syndrome.
AB  - Skin dysplasia, as cafe-au-lait spots, bone fibrous dysplasia and peripheral
      endocrinopathies are the main clinical features of McCune-Albright syndrome
      (MAS). This illness is due to activating mutations of the Gsalpha protein and is
      spread with a mosaic pattern in affected tissues that consist of intermixed areas
      of normal and mutated cells. Peripheral endocrine secretion, free of hypothalamic
      pituitary control, is the hallmark of the endocrine syndromes: precocious
      puberty, Cushing's syndrome, hyperthyroidism and gigantism/acromegaly. In
      addition, phosphate wasting as hyperphosphaturia is often present. The impact of
      hormonal hypersecretion and phosphate loss on the bones of patients with MAS is
      poorly understood both in normal and fibrous bone tissue. As hypercortisolism and
      hyperthyroidism increase bone resorption, hyperestrogenism and growth hormone
      hypersecretion stimulate bone growth and mineralization, and phosphate wasting
      reduces bone mineral content. All these actions can be exerted at varying times
      and degrees in a single patient on lesional and non-lesional bones. Sonographic
      evidence of multiple diffused hyperechogenic spots in the testes of patients with
      MAS do not seem to be related to alterations in calcium-phosphate metabolism but
      rather to zonal dysplasia/hyperplasia of testicular tissue.

PMID- 12199351
TI  - Use of bisphosphonates in children and adolescents.
AB  - The bisphosphonates are chemically simple compounds that have been used mainly
      for the treatment of osteoporotic conditions and for hypercalcaemia. They have
      had relatively limited use in children. Their action is principally to interfere
      with the activity of osteoclasts by causing apoptosis. Their use in children has
      been for problems of soft tissue calcification (e.g. idiopathic arterial
      calcification, myositis ossificans progressiva and dermatomyositis),
      hypercalcaemia (e.g. caused by malignancy, immobilisation or
      hyperparathyroidism), generalised bone disease (e.g. osteogenesis imperfecta,
      idiopathic juvenile osteoporosis and steroid-induced osteoporosis) and localised
      bone disease (e.g. Gaucher's disease and McCune-Albright syndrome). In general
      they cause few short-term side effects although the long-term side effects have
      yet to be determined, but are probably relatively unimportant. The
      bisphosphonates are likely to prove a useful addition to the armamentarium of
      treatment modalities for bone disease in children.

PMID- 12199352
TI  - Pamidronate treatment in bone fibrous dysplasia in children and adolescents with
      McCune-Albright syndrome.
AB  - Thirteen patients with McCune-Albright syndrome (MAS) and bone fibrous dysplasia
      (BFD) have been treated for 2-6 years with pamidronate, an aminobisphosphonate
      which inhibits osteoclastic function. MAS is a rare genetic condition caused by
      constitutive activating mutations of the Gs protein and manifests with skin
      dysplasia, bone fibrous dysplasia, and multiple endocrinopathies. Raised serum
      alkaline phosphatase and urinary hydroxyproline have been reported in these
      patients, indicating bone metabolic hyperactivity. Encouraging therapeutic
      results have been achieved with pamidronate, mainly in adults. In our study,
      treatment reduced bone pain, fracture rate and metabolic indices of bone
      turnover, in particular significantly decreased bone alkaline phosphatase and
      cross-links (Wilcoxon test; p <0.06), and increased bone mineral density (DEXA).
      Signs of healing, such as thickening of the cortical bone, were found in some
      patients. Three patterns of MRI were found: homogeneous hypointense fibrous
      tissue, 'dotted' hypointense fibrous tissue, and hyperintense cystic images.
      Pamidronate treatment can be considered a favorable therapeutic option for
      patients with MAS.

PMID- 12199353
TI  - Surgical treatment of fibrous dysplasia of bone in McCune-Albright syndrome.
AB  - Seven patients affected by McCune-Albright syndrome with polyostotic fibrous
      dysplasia were operated on either for fracture fixation or for correction of bone
      deformity. Ten femurs, three tibiae, and one humerus were stabilized by
      intramedullary titanium nailing with a modified unreamed femoral nail (UFN) and
      standard unreamed tibial (UTN) and humeral (UHN) nails. The age of the patients
      at operation ranged from 8 to 30 years, with an average of 17 years, and the
      length of follow-up ranged from 8 months to 4 years, with an average of 2 years.
      Before operation, each patient had suffered from a minimum of three fractures to
      a maximum of 12, with an average of six fractures. The femur was the most
      affected skeletal segment. Before surgery, two patients were wheelchair-dependent
      owing to their severe lower limb bone deformities. At follow-up, all the patients
      were painless and all were able to walk even though one had to wear a bilateral
      long leg brace and another had to ambulate with the aid of two crutches. No
      patient had had additional fractures after surgery. The main intra-operative
      technical problems of this demanding surgical procedure were: a) reaming of a new
      medullary canal through the fibrodysplastic bone; b) the amount of blood loss in
      femoral surgery that ranged from 800 to 2,500 ml.

PMID- 12199354
TI  - Effective aromatase inhibition by anastrozole in a patient with gonadotropin
      independent precocious puberty in McCune-Albright syndrome.
AB  - Testolactone is used to treat conditions with excessive estrogen synthesis, e.g.
      gonadotropin-independent precocious puberty in McCune-Albright syndrome (MAS).
      Unfortunately, daily treatment with testolactone requires 3 to 4 doses (10-20
      tablets) and even at these doses it is sometimes ineffective. We treated a
      patient with MAS (cafe-au-lait spots; thelarche at age 2- 6/12 yr; menarche at 5-
      5/12 yr; accelerated bone age [BA 10 yr]) with the highly selective aromatase
      inhibitor anastrozole (1 mg once per day). Tamoxifen 1 mg/kg per day was added
      for 1 year but was discontinued when an ovarian cyst developed with markedly
      elevated estradiol levels. Estradiol levels returned to normal after resuming
      anastrozole-only treatment and accelerated BA progressed only 6 months during 2
      1/2 years of treatment. The potent estrogen suppressive action and simple dosage
      regimen of anastrozole suggest it may be advantageous compared to other aromatase
      inhibitors such as testolactone or anti-estrogens.

PMID- 12199355
TI  - Molecular dynamics of polycrystalline cellobiose studied by solid-state NMR.
AB  - Molecular motions of polycrystalline cellobiose have been investigated by
      measuring proton spin-lattice relaxation times, T1 and T1rho, and the second
      moment, M2, in both protonated and D2O exchanged forms over the temperature range
      120-380 K. T1 relaxation is dominated by the motions of hydroxyl groups between
      150 and 380 K, characterised by an activation energy of about 8.74 kJ/mol,
      whereas T1rho relaxation is driven by the motions of the same groups between 120
      and 300 K. T1rho results suggest that hydroxyl groups have a distribution of
      dynamics. Motion of methylene groups was detected in the second-moment
      experiments at about 350 K, characterised by activation energy of about 40
      kJ/mol. Consideration of the calculated and observed rigid-lattice second moments
      suggests that the reported X-ray data are incorrect for the inter-proton distance
      on C6'. 13C CPMAS spectra of both protonated and deuterated cellobiose have also
      been measured. Spectra of the deuterated material showed the existence of a
      second crystalline form in addition to the normal form.

PMID- 12199358
TI  - Elemental quantitation of natural organic matter by CPMAS 13C NMR spectroscopy.
AB  - Cross-polarized magic-angle-spinning NMR (CPMAS-NMR) techniques are assumed to be
      only semi-quantitative in the assessment of carbon distribution in humic
      substances or natural organic matter, due to a number of interferences such as
      spinning side bands (SSB) in spectra, paramagnetic species in samples, and low or
      remote protonation of aromatic carbons. Fast rotor spin rates or direct
      polarization NMR techniques are normally applied to improve quantitative signal
      detectability. Variable contact time pulse sequences were used here to obtain
      CPMAS-NMR spectra of organic compounds of known structure and different humic
      substances. Integration of spectral areas, previously subtracted of SSB, and
      relative stoichiometric factors were used for mathematical elaboration to
      calculate the elemental content in samples. These values did not significantly
      differ from those obtained by direct determination of elemental content with
      quantitative elemental analysis. Our results showed that the carbon observed
      CPMAS-NMR provides a quantitative representation of the whole carbon content in
      humic substances.

PMID- 12199360
TI  - Solid-state 13C NMR study of poly(vinyl alcohol) gels.
AB  - Poly(vinyl alcohol) (PVA) with 55% and 61% syndiotacticity, and their related dry
      and hydrated gels obtained by two different freeze-thawing cycles have been
      investigated using the solid-state 13C CP-MAS NMR technique. From a comparative
      analysis of the spectra, evidence was obtained that the gelation process largely
      disrupts the intramolecular hydrogen-bonded network of the PVA. The addition of
      water to the dry gels favours their swelling, destroying intra-chain hydrogen
      bonds between hydroxyl groups as a function of the degree of tacticity and the
      gelation procedure, and promotes the formation of new networks of interchain
      hydrogen bonds. Information on the dynamics of the polymeric domains in the
      kilohertz range has been obtained from the analysis of the spin relaxation times
      T1rho(1H) and T1rho(13C) indicating that homogeneous arrangements of the
      amorphous or swollen polymeric chains exist, independent of the preparation
      method or the tacticity of the PVA chains.

PMID- 12199361
TI  - High-resolution solid-state 13C NMR studies of poly[(R)-3-hydroxybutyric] acid.
AB  - Solid poly[(R)-3-hydroxybutyric] acid was examined by high-resolution 13C MAS
      NMR, differential scanning calorimetry and infrared spectroscopy. The 13C methyl
      group resonance consists of three components: the rigid amorphous phase, the
      crystalline phase and the mobile amorphous phase. Spectral deconvolution, using
      the Lorentz function, reveals the relative amounts as 62% crystalline and 38%
      amorphous at 333 K, and 42% crystalline, 40% pure amorphous and 18% beta
      orthorhombic at 413 K. NMR indicates a large difference in molecular mobility
      between the crystalline and amorphous regions of the sample. Infrared
      spectroscopy shows that the stretching at 1725 cm(-1) (characteristic of the
      alpha-form) comes from the crystalline region, and the bands at 1744 cm(-1)
      (characteristic of the beta-form) and 1800 cm(-1) come from the amorphous region.

PMID- 12199362
TI  - Quarter milk somatic cell count in infected dairy cows: a meta-analysis.
AB  - The aim of this paper was to evaluate the effects associated with intramammary
      infection (IMI) by a bacterium or a group of bacteria (Staphylococcus aureus,
      Streptococcus agalactiae, Streptococcus dysgalactiae, Streptococcus uberis,
      coliforms, Staphylococci other than S. aureus, and Corynebacterium bovis) on the
      somatic cell count (SCC) in quarter milk of dairy cows. Papers selected for
      analysis had to provide SCC values associated with the natural infection in
      quarters by different bacteria. Sampling for measurement of SCC and determination
      of the infection had to be done on the same day. Only papers published in English
      or in French after 1971 were considered. Twenty-one papers fulfilled the
      selection criteria. The animals sampled, the measurement techniques for SCC and
      the bacteriological identification, as well as the definition of the infection,
      all differed widely among the selected studies. The meta-analysis method was used
      to estimate both the mean SCC (arithmetic and geometric) value and the average
      increase on SCC of each type of infection. The geometric mean SCC in
      bacteriologically negative quarters was 68 000 c/mL. In case of IMI, the retained
      SCC was 357 000, 857 000, 547 000, 1 024 000, 1 151 000, 138 000 and 105 000 c/mL
      in quarters infected by Staphylococcus aureus, Streptococcus agalactiae,
      Streptococcus dysgalactiae, Streptococcus uberis, coliforms, staphylococci other
      than S. aureus and Corynebacterium bovis, respectively. The variation factors
      that could influence these SCC values and the bacteriological results are
      discussed.

PMID- 12199363
TI  - Environmental and physico-chemical factors induce VBNC state in Listeria
      monocytogenes.
AB  - Investigations of bacterial survival in natural environments have indicated that
      some organisms lose culturability on appropriate media under certain conditions
      and yet still exhibit signs of metabolic activity and thus viability. This
      reproducible loss of culturability in many bacterial species led to the
      description of a "Viable But Non Culturable" (VBNC) state. The purpose of this
      article is to determine environmental and physico-chemical factors which induce
      the VBNC state in a food-borne pathogen that has become a public concern:
      Listeria monocytogenes. The factors, i.e. inoculum size, natural sunlight,
      temperature (4 degrees C or 20 degrees C), NaCl concentration (0% or 7%) and pH
      (5 or 6) were studied on 4 strains (LO28, ATCC 19115, Scott A, CNL 895807). The
      culturability of the starved cell suspension was determined in each condition
      tested by the spread plate count, and the cell activity was determined by the
      Direct Viable Count technique and CTC-DAPI double staining. A strain effect was
      found in different test conditions. For the LO 28 and ATCC 19115 strains, the
      VBNC state was very transient in certain conditions. For the other strains tested
      (Scott A, CNL 895807), the VBNC state was maintained throughout the observation
      period. In the dark, the incubation temperature was the main factor in the
      production of VBNC forms in L. monocytogenes. However, natural sunlight rapidly
      produced the VBNC state in L. monocytogenes cells in microcosm water. We conclude
      that because of its ubiquity and the factors studied which are met in the food
      industry, the presence of VBNC L. monocytogenes cells could pose a major public
      health problem since they cannot be detected by traditional culturing methods.
      Further investigations are needed to establish virulence before and after
      resuscitation of VBNC L. monocytogenes cells.

PMID- 12199364
TI  - Three-dimensional kinematics of the equine interphalangeal joints: articular
      impact of asymmetric bearing.
AB  - The objective of this study was to assess the effects of asymmetric placement of
      the foot on the three-dimensional motions of the interphalangeal joints. Four
      isolated forelimbs were used. Trihedrons, made of three axes fitted with
      reflective markers, were screwed into each phalanx. They allowed to establish a
      local frame associated with each bone and thus to define the spatial orientation
      of the phalanges. The limbs were then placed under a power press, and subjected
      to compression with gradually increasing force (from 500 to 6 000 N). The
      procedure was performed in neutral position and with the lateral or medial part
      of the foot raised by a 12 degrees wedge. Flexion, collateromotion (passive
      abduction/adduction) and axial rotation of the interphalangeal joints were
      measured using a cardan angle decomposition according to the principle of the
      "Joint Coordinate System" described by Grood and Suntay. Raising the lateral or
      medial part of the hoof induced collateromotion (about 5.6 degrees +/- 0.8) and
      axial rotation (about 6.5 degrees +/- 0.5) of the distal interphalangeal joint.
      The proximal interphalangeal joint underwent axial rotation (about 4.7 degrees +/
      0.5 at 6 000 N) and slight collateromotion. Both interphalangeal joints
      underwent collateromotion in the direction of the raised part of the foot (i.e.,
      narrowing of the articular space on the side of the wedge), whereas axial
      rotation occurred in the direction opposite to the raised part of the foot. These
      results confirm the functional importance of interphalangeal joint movements
      outside the sagittal plane. In particular they demonstrate the involvement of the
      proximal interphalangeal joint in the digital balance. These data are helpful for
      the identification of biomechanical factors that may predispose to
      interphalangeal joint injury. Also the data may be of use for the rational
      decision making with respect to exercise management and corrective shoeing of the
      lame horse.

PMID- 12199365
TI  - Differences in metabolic parameters and gene expression related to
      osteochondrosis/osteoarthrosis in pigs fed 25-hydroxyvitamin D3.
AB  - Osteochondrosis/osteoarthrosis (OC/OA) are common terms for various joint
      pathologies that occur in pigs. Pathologies that may contribute to these
      disorders have been described, but the primary cause(s) remain unknown. We
      hypothesised that as OC has some similarities to dyschondroplasia, which involves
      a failure of growth plate chondrocytes to fully differentiate and hypertrophy,
      treatment with 25-hydroxyvitamin D3 (25-D) might reduce the incidence and/or
      severity of lesions in pigs, as it does in chickens with dyschondroplasia.
      Control pigs were fed a commercial diet ad libitum. In the treated group this
      diet was supplemented with 25-D at 0.1 mg/kg. Ten pigs from each of the control
      and treated groups were sampled at 7, 12, 16 and 21 weeks. Treatment with 25-D
      had no effect on the incidence or severity of OC/OA lesions. Cartilage dry
      weight, total collagen content and proteoglycan content, and plasma levels
      oftotal calcium, inorganic phosphorous, vitamin C, insuline-like growth factor-I,
      parathyroid hormone and tumour necrosis factor alpha were unaffected by
      treatment. In addition, none of these parameters were correlated with the
      incidence or severity of OC/OA lesions. The mRNA expression levels of 21 out of
      23 genes assayed by RT-PCR were unaltered in articular cartilage from OA lesion
      samples as compared to normal articular cartilage. However, collagen type II was
      reduced and collagen type X increased in OA lesion and near lesion samples. These
      results suggest that OA in pigs may share some features of osteoarthritis in
      other mammalian species.

PMID- 12199366
TI  - Dot-enzyme linked immunosorbent assay as an alternative technique for the
      detection of bovine respiratory syncytial virus (BRSV) antibodies.
AB  - A dot-ELISA test for the detection of anti-BRSV antibodies is described. The
      objective of this study was the standardisation of a test as a fast, inexpensive
      and effective alternative to detect anti-BRSV antibodies. Its sensitivity,
      specificity and usefulness were compared to a commercial ELISA-kit and to the
      standard serum neutralisation (SN) test. The standardisation of the technique was
      done using nitrocellulose disks soaked with a viral sample isolated in Brazil,
      BRSV-25-BR. The best results were obtained when the disks were sensitised with a
      purified antigen at a concentration of 0.7 microg/disk and the bovine serum was
      diluted 1: 200. The experiment used 423 samples of bovine serum collected in the
      main cattle breeding centres in Brazil. The standard SN, dot-ELISA technique and
      commercial ELISA kits scored 67.8%, 71.8% and 72.3% of the samples as positive,
      respectively. When compared to the SN test, the standardised dot-ELISA and the
      commercial ELISA tests presented relative sensitivities of 92.3% and 91.6% and
      relative specificities of 71.3% and 68.4% respectively. The results demonstrated
      that the dot-ELISA test is adequate for the objectives proposed by this study,
      being easy to use and economically viable. Thus, this test represents an
      alternative for BRSV serological diagnosis in the substitution of SN and
      commercial ELISA tests, recommendable for utilisation in laboratories with few
      resources.

PMID- 12199367
TI  - Effect of diet on Shiga toxin-producing Escherichia coli (STEC) growth and
      survival in rumen and abomasum fluids.
AB  - The gastrointestinal tract of ruminants is the main reservoir for Shiga toxin
      producing Escherichia coli (STEC) strains, potentially pathogenic for humans. We
      used for the first timerumen fluid in which no exogenous carbon source or other
      supplement was added to compare acid resistance and growth of STEC in
      physiological physico-chemical conditions. We showed that acidic conditions
      resulting from the combination of high volatile fatty acid concentration and
      moderately acidic pH did not alter the survival of STEC, and that human non
      O157:H7 STEC isolates were able to persist in the rumen contents in spite of acid
      stress, low oxygen availability and nutrient deprivation, in the same manner as
      bovine STEC isolates do. Furthermore, our results support the hypothesis that a
      grain-rich diet may induce mechanisms of STEC acid resistance in the rumen that
      allow STEC survival in the abomasum.

PMID- 12199368
TI  - Bovine milk fat globules do not inhibit C5a chemotactic activity.
AB  - The C5a complement fragment is a potent inflammatory molecule but its
      contribution to the inflammatory response of the mammary gland remains uncertain.
      One of the unresolved questions is the possible interference of whole milk with
      C5a. In this study, the chemotactic activity ofpurifled bovine C5a was tested in
      the presence of whole or skimmed milk. Milk from healthy glands acted as a
      chemoattractant, which could mask any inhibitory effect on C5a activity. To
      circumvent milk activity, washed milk fat globules were incubated with optimal (1
      nM) or suboptimal (0.1 nM) concentrations of C5a, and the eventual
      chemoattractant activity was measured. There was no reduction in C5a-induced
      migration through a polycarbonate filter or shape-change of neutrophils. The
      concentrations of C5a determined by ELISA in the fluid phase were not reduced
      after incubation with the fat globules. It can be concluded that bovine milk fat
      globules do not trap or degrade C5a. Although these results do not explain the
      inhibitory effect of whole milk in the C5a-induced recruitment of neutrophils in
      milk, they suggest that milk does not inhibit the second major activity of C5a
      (apart from chemotaxis), i.e. the stimulation of phagocytic and bactericidal
      activities of neutrophils.

PMID- 12199369
TI  - Epidemiology of bovine tick-borne diseases in southern Italy.
AB  - This investigation was carried out in an area covering part of three southern
      Italian regions: Campania, Basilicata and Apulia. Eighty-one farms were involved
      using the formula suggested by Thrusfield; they were equally distributed over the
      area which was subdivided into 81 geo-referenced sub-areas. In May and June 1999
      from a total of 506 cattle, older than 18 months, blood-samples were taken and
      ticks were collected and identified. Serum samples were tested for antibodies of
      Bahesia bigemina, Babesia bovis and Anaplasma marginale with an ELISA technique.
      Eight farms (9.8%) out of the 81 examined were positive for B. bigemina only, 3
      (3.7%) for A. marginale only, and 70 (86.4%) for both. None of the animals of any
      farm was found to be positive for B. bovis. Out of the 506 sera tested, 117 (23.1
      %) were positive for B. bigemina only, 58 (11.5%) forA. marginale only and 250
      (49.4%) for both species; 81 (16.0%) were negative for all of them. Ticks were
      collected on animals on 62 (76.5%) out of the 81 farms. Adult ticks (1 410) were
      collected and identified; the highest number belonged to the Rhipicephalus bursa
      species (65.5%), followed by Rhipicephalus turanicus (8.6) and Haemaphysalis
      punctata (8.4). The results showed that B. bigemina, A. marginale and their
      potential vectors are common in the area examined and indicated that there is a
      risk for animals imported from tick-borne disease-free areas.

PMID- 12199370
TI  - Sheep as a new experimental host for Babesia divergens.
AB  - Babesia divergens was cultivated in sheep erythrocytes in RPMI 1640 supplemented
      with 10% Fetal Calf Serum (FCS) or sheep serum. In vitro cultures in sheep red
      blood cells were initiated with human erythrocytes infected in vitro with B.
      divergens Rouen 1987 or with gerbil blood infected with several isolates from
      bovine origin. After the first subcultures on sheep erythrocytes, a ten-fold
      multiplication of the parasites was obtained within 48 h. Erythrocytes from three
      splenectomized sheep were infected in vitro with B. divergens; when parasitaemia
      reached 10%, the animals were inoculated with homologous parasitized
      erythrocytes. All sheep expressed hyperthermia with a peak between the 6th and
      the 9th day post-infection (p-i) and a transitory parasitaemia 10 days p-i. In
      vitro primary cultures were performed on two of these sheep, demonstrating the
      parasite persistence at very low parasitaemia in the infected animals.
      Splenectomized sheep can be used as a new model for B. divergens chronic
      infection.

PMID- 12199371
TI  - The effect of jugular or abomasal infusion of amino acids on milk yield in
      lactating cows fed a protein deficient diet.
AB  - The influence of first-pass splanchnic metabolism was investigated by comparing
      the response of 5 lactating cows to an infusion of an amino acid mixture into the
      abomasum or a jugular vein over 5 d according to a complete block design. The
      basal diet and the amino acid infusion provided 71% and 14% of crude protein
      requirements, respectively. The jugular infusion increased (P = 0.01) milk yield
      by 0.80 kg in comparison to the abomasal infusion, but milk protein yield was not
      altered. The jugular infusion tended to increase (P = 0.06) the arterial
      concentration of total essential amino acids by 11% relatively to the abomasal
      infusion. Mammary plasma flow and net fluxes of amino acids and glucose were not
      affected by the infusion sites. Variations in essential amino acid concentrations
      suggest that splanchnic metabolism alters peripheral delivery of amino acids but
      the recirculation of amino acids within the animal decreased the impact of the
      first-pass splanchnic metabolism on lactational performances.

PMID- 12199372
TI  - Pre-implantational timetable of embryonal development of Myocastor coypus
      (Coypu).
AB  - The purpose of the present study was to determine the chronology of the pre
      implantation embryonic development in Myocastor coypus (coypu). It was carried
      out by daily colpocytological examination and controlled mating of 33 females.
      Oocytes and embryos were obtained by flushing from day 0 to day 10 post-coitus
      (p.c.). On day 1 p.c., oocytes predominated whereas on day 2 p.c. zygotes were
      predominant. The cleavage period was from day 3 to day 6 p.c.. Morulae were
      collected from day 6 to day 9 p.c., whereas blastocysts were collected on days 8
      and 9. From oviduct flushing, the embryos in the zygote stage and up to the
      morula stage with less than a 30-cell stage were recovered. Embryos in the morula
      stage with 30 or more cells and up to the growing blastocyst stage were collected
      from the flushing of hemiuteri.

PMID- 12199373
TI  - Dietary magnesium increases calcium absorption of ovine small intestine in vivo
      and in vitro.
AB  - The purpose of this study was to investigate whether or not an increase in
      dietary Mg intake increases Ca absorption in the ovine gastrointestinal tract. In
      an in vivo experiment, an increase in the infused MgCl2 level (0.0, 25.0 and 75.0
      mg Mg x kg BW(-1) x day(-1) with 75.0 mg Ca x kg BW(-1) x day(-1) as CaCl2) into
      the rumen for ten days significantly decreased fecal excretion but increased
      urinary excretion (P < 0.05) of Ca in five castrated male sheep. Apparent Ca
      absorption tended to increase (P = 0.067) whilst the retention and plasma
      concentration of Ca were not changed. In an in vitro experiment with isolated
      segments from the rumen, upper jejunum, cecum and upper colon under the presence
      of an electrochemical gradient, the mucosal to serosal Ca flux rate was
      significantly greater in the presence of 60.0 mM as compared with 1.2 mM MgCl2 (P
      < 0.05). From these results, we conclude that the mucosal Mg has the ability to
      increase the Ca absorption in the gastrointestinal tract in sheep when the
      dietary Mg level is raised.

PMID- 12199374
TI  - Effect of growth factors on proliferation, apoptosis and protein kinase A
      expression in cultured porcine cumulus oophorus cells.
AB  - The proliferation, apoptosis and protein kinase A (PKA) in porcine cumulus
      oophorus (CO) before and after 40 h of culture together with oocytes in the
      presence of IGF-I, IGF-II and EGF (all at 10 ng x mL(-1) medium) were compared.
      Cellular proliferation, apoptosis and PKA contents were evaluated by
      immunocytochemistry using specific antibodies against PCNA, TUNEL and catalytic
      (C-alpha) and regulatory (RI) subunits of PKA. The in-vitro culture of oocyte-CO
      complexes in a basal medium was accompanied by a decrease in the proportion of
      PCNA-positive CO cells (from 51 to 36%, p < 0.05). The addition of either IGF-I
      or EGF to the culture medium prevented this process and increased the
      proliferation rate (64 and 67% respectively, p < 0.001). During culture, the
      percentage of apoptotic (TUNEL-positive) CO cells increased from 42 to 57% (p <
      0.01). The addition of IGF-I or EGF resulted in the inhibition of apoptosis to 36
      and 12% respectively (p < 0.001). IGF-II and EGF reduced the amount of PKA
      catalytic subunits in the CO (percentage of cells with immunoreactive PKA
      catalytic subunits (28%, p < 0.05 and 27%, p < 0.05 respectively; versus control 
      41%), whilst the effect of IGF-I on this index was insignificant (31%). The
      expression of the PKA regulatory subunit was increased by EGF (51% compared with
      29% in the control, p < 0.05), but not by IGF-I or IGF-II (30 and 29%). Our
      observations demonstrate that 40 h of culture of porcine CO resulted in a
      decrease in the proliferation and development of apoptosis in CO cells. IGF-I or
      EGF can stimulate proliferation and inhibit apoptosis. The influence of growth
      factors on the PKA content of the CO suggests that cAMP/PKA may be a mediator of
      the action of growth factors on these cells. The differential effects of IGFs and
      EGF on the regulatory subunit of PKA may indicate differences between their
      mechanisms of action.

PMID- 12199375
TI  - Effects of high temperature on body temperature and hormonal adjustments in
      piglets.
AB  - Effects of a high (33 degrees C) or thermoneutral (23 degrees C) temperature on
      body temperature and endocrine parameters were studied in weaned piglets. Rectal
      and skin temperatures were measured in four ad libitum fed animals per
      temperature during three weeks. After this acclimation period, 11 blood samples
      were withdrawn on a 24-h period. Over the acclimation period, rectal and skin
      temperatures were 0.6 and 2.9 degrees C higher, respectively, at 33 degrees C
      than at 23 degrees C (P < 0.01), this change occurring from the 1st day at 23 or
      33 degrees C. A tendency of serum leptin concentrations to be lower after meals
      at 33 degrees C than at 23 degrees C was also displayed (P = 0.09). Plasmatic
      concentrations in Insulin-like growth factor I and thyroxine were decreased at 33
      degrees C relative to 23 degrees C (P < 0.01 and P < 0.06, respectively), and
      triiodothyronine concentrations tended to be lower at 33 degrees C than at 23
      degrees C (P = 0.1), which could account for the lower heat production and growth
      observed in pigs exposed to high temperatures.

PMID- 12199376
TI  - Growth and cell cycle regulation by isoflavones in human breast carcinoma cells.
AB  - The isoflavones daidzein and biochanin A induced a biphasic growth response in T
      47D human breast cancer cells. At growth stimulatory concentrations, daidzein
      increased the percentage of cells entering the S phase, while at a growth
      inhibitory concentration, daidzein obstructed the progression of the cell cycle
      in the G2/M phase. Biochanin A regulated the cell cycle progression in a similar
      manner and showed a delay in the progression from the S phase to the G2/M phase
      at growth inhibitory concentrations. The levels of a cell cycle regulatory
      protein, P53, in response to the treatment of isoflavones, were also determined.
      Cells that became de-attached and floated in the medium after treatment with
      growth inhibitory concentrations of daidzein or biochanin A, showed higher P53
      levels than cells that remained attached. These results suggest that daidzein and
      biochanin A influence T-47D cell proliferation and cell cycle progression, and
      that the underlying mechanisms might be associated with the P53 protein levels.

PMID- 12199377
TI  - Major constituents, leptin, and non-protein nitrogen compounds in mares'
      colostrum and milk.
AB  - Five Haflinger mares were hand-milked at 0 h (pre-suckle) and 6 h (postsuckle),
      12, 24, 48, 72 and 96 h after parturition. Total solids, protein, fat, lactose,
      calculated gross energy content, leptin and non-protein nitrogen components
      (urea, alpha-amino nitrogen, creatinine and allantoin) were determined. The
      levels of the major constituents differed significantly in pre-suckle colostrum
      from subsequent samples. Leptin levels were the highest in whole (9 ng x mL(-1)
      of immunoreactive human equivalent HE +/- 0.48 ng x mL(-1), SEM) and skimmed (7.8
      ng HE x mL(-1) +/- 0.52 ng x mL(-1), SEM) pre-suckle colostrum, declined sharply
      at 6 hours postpartum, and more slowly subsequently. Mean urea concentration was
      constant at around 5.0 mM, while a-amino N increased over the observation period
      and creatinine and allantoin decreased. These findings provide a further
      indication that mares' milk can be regarded as a functional food.

PMID- 12199378
TI  - Cryopreservation of bovine oocytes: is cryoloop vitrification the future to
      preserving the female gamete?
AB  - The cryoloop is a technique where a thin nylon loop is used to suspend a film of
      cryoprotectant containing the oocytes and directly immersing them in liquid
      nitrogen. 508 bovine oocytes were collected, of these 351 were cryopreserved by
      slow freezing using standard straws or a new vitrification method using our self
      constructed cryoloops and the remainder were controls. After thawing, the oocytes
      were inseminated by ICSI or standard IVF. The cryoloop vitrification method
      yielded a survival rate of 90.5% and the slow freezing technique a rate of 54.4%
      (p < 0.0001). When ICSI was performed, cryopreservation by the cryoloop
      vitrification method resulted in very similar cleavage rate to controls (16.0%
      vs. 17.3%) but slow freezing produced a slightly lower rate (9.4%). Cleavage
      rates after IVF in fresh oocytes was higher than the cryopreservation groups
      (49.5% vs. 15.4% and 25.8%), whereas after ICSI the rates were similar in all
      groups (17.3% vs. 9.4% and 16%). It is concluded that the new cryoloop
      vitrification technique followed by ICSI produce good embryo formation results
      and they could hold the future for effective oocyte cryopreservation.

PMID- 12199379
TI  - Lessons from a wedding.

PMID- 12199380
TI  - Use of bone graft substitutes in lower extremity reconstructive surgery.
AB  - Autologous iliac crest graft has been a standard source of supplementary bone for
      treating bony defects, fractures and arthrodeses. Bone graft substitutes have
      recently become widely available. This paper reports on the use of bone graft
      substitute in 28 patients that otherwise would have required an iliac crest
      graft. Twenty-four of the 28 operations were successful in the primary procedure
      with four patients requiring a second procedure that was then successful.

PMID- 12199381
TI  - Treatment of talar osteochondral lesions using local osteochondral graft.
AB  - Twelve patients with an osteochondral lesion of the talus were treated with
      excision of the lesions and local osteochondral autogenous grafting. The lesion
      was accessed through a replaceable bone block removed from the anterior tibial
      plafond. The graft was harvested from the medial or lateral talar articular facet
      on the same side of the lesion. The average age of the patients was 41 years and
      duration of symptoms was 90 months (ave.). There were six males and six females
      with the right talus involved in eight and the left in four patients. Graft sizes
      ranged from four to eight millimeters in diameter. There was a significant
      improvement in the AOFAS score from 64.4 (ave.) pre-operatively to 90.8 (ave.)
      postoperatively (p<0.0001), at a follow-up of 25.3 months (ave.). The AOFAS score
      was slightly higher in patients under 40 years of age and in those without pre
      existing joint arthritis. All patients were very satisfied with the procedure.
      Arthroscopy performed in two patients at six and 12 months following surgery
      showed good graft incorporation. No complications occurred at the donor site or
      the site of bone block removal on the distal tibia. The results show that stage
      III and IV talar osteochondral lesions can be accessed successfully excising a
      tibial bone block and using local autogenous osteochondral graft harvested from
      the ipsilateral talar articular facet.

PMID- 12199382
TI  - Keller resection arthroplasty for treatment of hallux valgus deformity: increased
      correction with fibular sesamoidectomy.
AB  - Thirty-eight patients (50 feet) were treated with Keller resection arthroplasties
      combined with fibular sesamoidectomies. Thirty-six patients were females (48
      feet) and two were males (two feet). Their ages ranged from 55 to 87 years and
      averaged 68.4 years. Preoperative metatarsophalangeal (MTP) angles averaged 34
      degrees (range, 10 to 55 degrees) and intermetatarsal (IM) angles averaged 15
      degrees (range, 8 to 27 degrees). All patients were evaluated at an average of
      three years after surgery. An average correction of 18 degrees in the MTP angle
      and 6 degrees in the IM angle were obtained. At follow-up, 76% of patients had no
      pain, 14% had mild pain, and 10% had moderate pain; 76% had no activity
      limitations, 22% had recreational limitations, and 2% had daily limitations.
      Ninety-five percent of patients were satisfied with the results of their surgery.

PMID- 12199383
TI  - The use of a 95 degree blade plate and a posterior approach to achieve
      tibiotalocalcaneal arthrodesis.
AB  - Various types of internal fixation have been used to achieve arthrodesis of both
      the ankle and subtalar joints. We have investigated the use of a standard 95
      degree angled blade plate as a method of more rigid internal fixation to achieve
      arthrodesis of these joints. The purpose of this retrospective study was to
      review our clinical and radiographic results in adults using a blade plate
      applied through a posterior approach to fuse the ankle and subtalar joints.
      METHODS: Between April 1995 and June 2000, 10 tibiotalocalcaneal arthrodeses were
      performed using a posterior approach and a blade plate for internal fixation.
      There were 10 adults (five men and five women) whose average age was 64 years
      (range, 42 to 80 years). The indication for the procedure was severe pain which
      was unresponsive to nonoperative management in patients with arthritic joints.
      Preoperative diagnoses included six patients with post-traumatic arthritis, two
      with primary degenerative arthritis, one with rheumatoid arthritis, and one with
      post-polio deformity. An average of 1.7 previous operations had been performed on
      the affected ankle. RESULTS: Clinical and radiographic follow-up was performed
      for all patients at an average of 37 months (range, 12 to 71 months)
      postoperatively. All 10 patients achieved a solid fusion. The mean time to
      radiographic fusion was 14.5 weeks (range, 9 to 26 weeks). The operation resulted
      in plantigrade feet in all patients with an average tibia-floor angle of 2.3
      degrees of dorsiflexion and an average of 5 degrees of hindfoot valgus. Patients
      had excellent pain relief, however function did not improve as much.
      Complications occurred in three patients. One patient required a small split
      thickness skin graft for wound healing, one experienced a transient posterior
      tibial nerve neuropraxia, and one developed a deep venous thrombosis in the
      nonoperative leg at six weeks postoperatively. Three patients required removal of
      the blade plate because of discomfort, which promptly cleared. CONCLUSIONS:
      Arthrodesis provides excellent pain relief for patients with painful arthritic
      deformities of the ankle and subtalar joints. Using a posterior approach, a blade
      plate for internal fixation and bone grafts resulted in a solid fusion for all
      our patients. This method is particularly effective in large patients with a mild
      moderate hindfoot deformity.

PMID- 12199384
TI  - Mechanical comparison of cyclic loading in five different first metatarsal shaft
      osteotomies.
AB  - The purposes of the current study were: 1. to analyze the relative fatigue
      endurance of five different first metatarsal shaft osteotomies (proximal
      crescentic, proximal chevron, Ludloff, Mau, and Scarf), as performed on sawbone
      models using the most common fixation techniques (part I); and 2. to compare the
      two more commonly used techniques (per part I results) in matched-pair cadaver
      specimens (part II). In part I, the proximal chevron and Mau osteotomies were
      significantly more stable (P < or = 0.005) than all other osteotomies except the
      Ludloff. In part II, there was no significant difference in fatigue endurance
      between the proximal chevron and Ludloff osteotomies.

PMID- 12199385
TI  - The first intermetatarsal angle in hallux valgus: an analysis of measurement
      reliability and the error involved.
AB  - In view of the importance placed on the first intermetatarsal angle in the
      assessment of surgical intervention in hallux valgus, we assessed the reliability
      with which one measures this angle. The study involved 10 observers of varying
      experience measuring the angle using a standard technique on 10 weightbearing AP
      X-rays of the foot on three separate occasions. The margin of error in measuring
      the angle was +/-3.60 degrees with a 95% confidence interval. Increasing and
      averaging the number of readings per observer or the readings of a number of
      observers, reduces the error. Experience doesn't improve reliability. In
      conclusion, improvement in the reliability of the measurements can be achieved by
      careful technique, performing the measurements at least twice, and averaging
      them.

PMID- 12199386
TI  - Intra- and inter-observer reliability of the distal metatarsal articular angle in
      adult hallux valgus.
AB  - There is some uncertainty as to whether the distal metatarsal articular angle
      (DMAA) is a real entity or just radiographic artifact and whether it can be
      reliably measured. If it is intrinsic to the bone, it should not change with bone
      position. If it is clinically useful, it should be reproducible. Pre-operative
      and post-operative radiographs of 32 patients undergoing a proximal bony
      procedure of the first ray were evaluated independently by three foot and ankle
      specialists in order to determine the intra and inter-observer reliability of the
      distal metatarsal articular angle (DMAA). In addition, the hallux valgus angle
      (HVA), intermetatarsal angle (IMA) and joint congruency/subluxation were
      determined. We used ANOVA (Scheffe's F-test) to determine reliability of the
      angular measurements; a p value of less than 0.05 indicates poor reliability and
      a p value of greater than 0.05 indicates reliability. Intra-observer reliability
      was good for all angular measurements (HVA, IMA, DMAA pre-op, and DMAA post-op)
      with p values ranging from 0.33 to 0.95. Inter-observer reliability of the HVA
      and IMA was good (p=0.63 and p=0.32). Inter-observer reliability of the pre-op
      DMAA approached statistically poor reliability (p=0.09) and the post-op DMAA
      reliability was poor (p=0.002). The DMAA reduced after the proximal procedure as
      measured by all observers, and averaged a reduction of 3.9 degrees. Weighted
      kappa analysis also revealed that there was poor agreement in the determination
      of congruency and subluxation (Kappa statistic ranged from 0.07 to 0.19). This
      study suggests that there may be limited value in the DMAA as a clinical measure
      as it varies with examiner and with the hallux valgus angle.

PMID- 12199387
TI  - Biomechanical evaluation of the efficacy of external stabilizers in the
      conservative treatment of acquired flatfoot deformity.
AB  - This study quantified and compared the efficacy of in-shoe orthoses and ankle
      braces in stabilizing the hindfoot and medial longitudinal arch in a cadaveric
      model of acquired flexible flatfoot deformity. This was addressed by combining
      measurement of hindfoot and arch kinematics with plantar pressure distribution,
      produced in response to axial loads simulating quiet standing. Experiments were
      conducted on six fresh-frozen cadaveric lower limbs. Three conditions were
      tested: intact-unbraced; flatfoot-unbraced; and flatfoot-braced. Flatfoot
      deformity was created by sectioning the main support structures of the medial
      longitudinal arch. Six different braces were tested including two in-shoe
      orthoses, three ankle braces and one molded ankle-foot orthosis. Our model of
      flexible flatfoot deformity caused the calcaneus to evert, the talus to
      plantarflex and the height of the talus and medial cuneiform to decrease.
      Flexible flatfoot deformity caused a pattern of medial shift in plantar pressure
      distribution, but minimal change in the location of the center of pressure.
      Furthermore, in-shoe orthoses stabilized both the hindfoot and the medial
      longitudinal arch, while ankle braces did not. Semi-rigid foot and ankle orthoses
      acted to stabilize the medial longitudinal arch. Based on these results, it was
      concluded that treatment of flatfoot deformity should at least include use of in
      shoe orthoses to partially restore the arch and stabilize the hindfoot.

PMID- 12199388
TI  - The impact of instrumented gait analysis on surgical planning: treatment of
      spastic equinovarus deformity of the foot and ankle.
AB  - BACKGROUND: Despite the logic behind instrumented gait analysis, its specific
      contribution to clinical and surgical decision making is not well known. Our
      purpose in this study was to determine the influence of gait analysis with
      dynamic electromyography upon surgical planning in patients with upper motor
      neuron syndrome and gait dysfunction. METHODS: Two surgeons prospectively
      evaluated 36 consecutive adult patients with a spastic equinovarus deformity of
      the foot and ankle. After an initial history and physical exam, each surgeon
      independently formulated a surgical plan. Surgical treatment options for each
      individual muscle/tendon unit crossing the ankle included lengthening, transfer,
      release or no surgery. After the initial clinical evaluation and surgical
      planning, all patients then underwent instrumented gait analysis collecting
      kinetic, kinematic and poly-EMG data using a standard protocol by a single
      experienced physiatrist. Each surgeon reviewed the gait studies and patients
      independently and again formulated a surgical plan. The surgical plans were
      compared for each surgeon before and after gait study. The agreement between the
      two surgeon's surgical plans was also compared before and after gait study. Each
      patient was evaluated for the clinical outcome of surgery. RESULTS: Overall a
      change was made in 64% of the surgical plans after the gait study. The frequency
      of changing the surgical plan was not significantly different between the more
      and less experienced surgeons. The agreement between surgeons increased from 0.34
      to 0.76 (p=0.009) after the gait study. The number of surgical procedures planned
      by each surgeon converged after the gait studies. Correction of the varus
      deformity was seen in all patients that underwent surgical treatment. CONCLUSION:
      Instrumented gait analysis alters surgical planning for patients with equinovarus
      deformity of the foot and ankle and can produce higher agreement between surgeons
      in surgical planning. CLINICAL RELEVANCE: The equinovarus deformity is due to a
      variety of deforming forces and a single, best operation does not exist to
      correct all equinovarus deformities. Rather, a muscle specific approach that
      identifies the deforming forces will produce the best outcomes when treating the
      spastic equinovarus deformity.

PMID- 12199389
TI  - Ruptured tibio-fibular syndesmosis: comparison study of metallic to bioabsorbable
      fixation.
AB  - The patients of this study come from a series of 43 consecutive ankle fracture
      patients with syndesmotic rupture operated on at our department. Of these
      patients, 18 were treated with bioabsorbable self-reinforced poly-L-lactide screw
      and 12 treated with metallic screw. All agreed to participate in this study. They
      were examined after a minimum follow-up period of 12 months. The patients were
      examined for measurements from ankle radiographic and computed tomography films,
      loaded dorsal range of movement of the ankle, and duration of sick leave.
      Subjective results were obtained by a constructed questionnaire. There were no
      significant differences between the patient groups in any of the parameters
      measured. We conclude that the fixation of a syndesmotic rupture can be done with
      a bioabsorbable self-reinforced poly-L-lactide screw.

PMID- 12199390
TI  - Continuous lateral sciatic blocks for acute postoperative pain management after
      major ankle and foot surgery.
AB  - We developed a continuous lateral sciatic nerve infusion technique for
      postoperative analgesia. METHODS: A 10-cm insulated Tuohy needle connected to a
      nerve stimulator was introduced posteriorly between the biceps femoris and vastus
      lateralis groove 10 cm cephalad from the tip of the patella. After proper
      positioning of the insulated needle, a 20-gauge catheter was placed in proximity
      to the sciatic nerve. RESULTS: Continuous lateral sciatic infusion of 0.2%
      ropivacaine was associated with a significant reduction of morphine consumption
      by 29% and 62% during postoperative days one and two, respectively, in patients
      who underwent open reduction and internal fixation of the ankle. CONCLUSION:
      Continuous lateral sciatic infusion of 0.2% ropivacaine represents an alternative
      for acute postoperative pain control after major ankle and foot surgery.

PMID- 12199391
TI  - An easy way of tensioning and securing a tendon to bone.

PMID- 12199392
TI  - Report of the AOFAS Outreach and Educational Fund's Overseas Fellowship to
      Vietnam, June 2-30, 2002.

PMID- 12199393
TI  - Sustaining a constant effort by the tongue and hand: effects of acute fatigue.
AB  - A constant-effort task was used previously as a potential assessment technique
      for fatigue. Participants sustained submaximal target effort levels with the
      tongue and hand against soft air-filled bulbs. For 80% of all trials, pressure
      decreased exponentially to a positive asymptote. In addition, pressure decreased
      faster when the muscles were fatigued than when they were rested. This study
      attempted to replicate the previous findings with new participants and to extend
      the findings to include surface electromyographic (EMG) data. Pressure and
      surface EMG signals were collected simultaneously while 10 neurologically normal
      young adults performed the constant-effort task at 50% of maximum pressure with
      the tongue and the hand. Eighty-one percent of the pressure data were modeled by
      a negative exponential equation with a nonzero asymptote. Seventy-three percent
      of the corresponding EMG data also fit this mathematical model. The pressure
      signals decayed more slowly than the corresponding EMG signals, particularly for
      the hand. After participants fatigued the tongue and hand with repeated brief
      maximal voluntary contractions, the time constants were reduced (rate of decay
      increased) for the tongue but not the hand. These results corroborate the
      previous finding that the time constant, determined from an exponential curve
      fitting procedure, is a replicable measure. Furthermore, the reduction in the
      time constant after inducing acute fatigue in the tongue was replicated, although
      this same relationship was not replicated for the hand. The EMG data suggest that
      decreases in neuromuscular drive, including increased early adaptation, motor
      unit derecruitment, and motor unit desynchronization, contributed to the decrease
      in pressure during the constant-effort task, especially after acute fatigue was
      induced. These observations support the hypothesis that the task reflects, at
      least in part, central fatigue processes.

PMID- 12199394
TI  - Voice amplification versus vocal hygiene instruction for teachers with voice
      disorders: a treatment outcomes study.
AB  - Voice problems are common among schoolteachers. This prospective, randomized
      clinical trial used patient-based treatment outcomes measures combined with
      acoustic analysis to evaluate the effectiveness of two treatment programs. Forty
      four voice-disordered teachers were randomly assigned to one of three groups:
      voice amplification using the ChatterVox portable amplifier (VA, n = 15), vocal
      hygiene (VH, n = 15), and a nontreatment control group (n = 14). Before and after
      a 6-week treatment phase, all teachers completed: (a) the Voice Handicap Index
      (VHI), an instrument designed to appraise the self-perceived psychosocial
      consequences of voice disorders; (b) a voice severity self-rating scale; and (c)
      an audiorecording for later acoustic analysis. Based on pre- and posttreatment
      comparisons, only the amplification group experienced significant reductions on
      mean VHI scores (p = .045), voice severity self-ratings (p = .012), and the
      acoustic measures of percent jitter (p = .031) and shimmer (p = .008). The
      nontreatment control group reported a significant increase in level of vocal
      handicap as assessed by the VHI (p = .012). Although most pre- to posttreatment
      changes were in the desired direction, no significant improvements were observed
      within the VH group on any of the dependent measures. Between-group comparisons
      involving the three possible pairings of the groups revealed a pattern of results
      to suggest that: (a) compared to the control group, both treatment groups (i.e.,
      VA and VH) experienced significantly more improvement on specific outcomes
      measures and (b) there were no significant differences between the VA and VH
      groups to indicate superiority of one treatment over another. Results, however,
      from a posttreatment questionnaire regarding the perceived benefits of treatment
      revealed that, compared to the VH group, the VA group reported more clarity of
      their speaking and singing voice (p = .061), greater ease of voice production (p
      = .001), and greater compliance with the treatment program (p = .045). These
      findings clearly support the clinical utility of voice amplification as an
      alternative for the treatment of voice problems in teachers.

PMID- 12199395
TI  - Speech synthesis using damped sinusoids.
AB  - A speech synthesizer was developed that operates by summing exponentially damped
      sinusoids at frequencies and amplitudes corresponding to peaks derived from the
      spectrum envelope of the speech signal. The spectrum analysis begins with the
      calculation of a smoothed Fourier spectrum. A masking threshold is then computed
      for each frame as the running average of spectral amplitudes over an 800-Hz
      window. In a rough simulation of lateral suppression, the running average is then
      subtracted from the smoothed spectrum (with negative spectral values set to
      zero), producing a masked spectrum. The signal is resynthesized by summing
      exponentially damped sinusoids at frequencies corresponding to peaks in the
      masked spectra. If a periodicity measure indicates that a given analysis frame is
      voiced, the damped sinusoids are pulsed at a rate corresponding to the measured
      fundamental period. For unvoiced speech, the damped sinusoids are pulsed on and
      off at random intervals. A perceptual evaluation of speech produced by the damped
      sinewave synthesizer showed excellent sentence intelligibility, excellent
      intelligibility for vowels in /hVd/ syllables, and fair intelligibility for
      consonants in CV nonsense syllables.

PMID- 12199396
TI  - Tongues and lips without jaws: a comparison of methods for decoupling speech
      movements.
AB  - Speech-related motions of small markers attached to the tongue, lower lip, and
      lower jaw of 44 normal young adult talkers of American English were analyzed to
      estimate the relative accuracy of selected methods for decoupling tongue and lip
      motions from ongoing jaw motion when all movements are originally measured
      relative to a common reference frame (such as the head). In general, results of
      the analysis show that a common "simple subtraction" method that ignores pitching
      rotation of the jaw yields larger errors in positions and speeds of decoupled
      tongue and lip markers than methods that do not ignore rotation. When the jaw is
      widely opened, is moving quickly, and/or when any decoupled marker is relatively
      far from the origin of a local coordinate system fixed to the jaw, positional and
      speed errors associated with the subtraction method can exceed 5 mm and 25 mm/s,
      respectively. We propose a simple procedure for estimating the pitching rotation
      of the jaw that can be applied when pitch cannot be measured. We then show that
      decoupled motions of tongue and lower lip markers based on estimated jaw rotation
      involve less error than those derived from any other decoupling method
      considered. Careful attention to processing methods should yield more accurate
      inferences about the nature and degree of coordination between speech-related
      movements of the tongue and lower lip that are decoupled from, and hence
      independent of, concurrent movements of the lower jaw.

PMID- 12199397
TI  - Articulatory control of vowel length for contiguous jaw cycles: the effects of
      speaking rate and phonetic context.
AB  - The current study examined contiguous cycles of jaw movement in order to
      determine if select suprasegmental manipulations operate globally across the
      entire utterance, while phonetic changes are more locally administered.
      Specifically, articulatory kinematics were examined to determine if intra- and
      inter-articulatory spatial and temporal organization across manipulations of
      speaking rate was maintained for both jaw cycles while differing between the two
      cycles for phonetic changes (i.e., in coda composition) specific to the second
      jaw cycle. Five normal speakers repeated the syllables /paep/, /paeps/, and
      /paepst/, embedded in the carrier phrase, "Now say again," using slow, normal,
      and fast speaking rates. Measures were made of the magnitude of jaw opening peak
      velocity and time to peak velocity, as well as of coarticulatory overlap and
      interarticulator timing, for the first jaw cycle (jaw lowering for /eI/ in "say"
      to the first /p/) and the second jaw cycle (jaw lowering for /ae/ to the second
      /p/). The current data indicate that, for intra-articulatory kinematics, the
      manipulation of phonetic context resulted in localized adjustments, whereas the
      manipulation of speaking rate was applied globally across the utterance.
      Conversely, for inter-articulatory kinematics, the upper lip-jaw synergy was
      reconfigured across the utterance for manipulations of speaking rate, whereas
      this synergy was maintained for localized manipulations in phonetic context.
      Results are discussed with respect to motor strategies being flexibly implemented
      as a result of contextual variation and speech rate.

PMID- 12199398
TI  - Coarticulation and formant transition rate in young children who stutter.
AB  - The purpose of this study was to assess anticipatory coarticulation and second
      formant (F2) transition rate (FTR) of speech production in young children who
      stutter (CWS) and who do not stutter (CWNS). Fourteen CWS and 14 age- and gender
      matched CWNS in three age groups (3-, 4-, and 5-year-olds) participated in a
      picture-naming task that elicited single-word utterances. The initial consonant
      vowel (CV) syllables of these utterances, comprising either bilabial [b m] or
      alveolar [d n s z] consonants and a number of vowels [i I e epsilon ae u o c aI
      av],were used for acoustic analysis. To assess coarticulation and speech movement
      velocity, the F2 onset frequency and F2 vowel target frequency (for
      coarticulation) and FTR (for speech movement velocity) were computed for each CV
      syllable and for each participant. Based on these measures, locus equation
      statistics of slope, y-intercept, and standard error of estimate as well as the
      FTR were analyzed. Findings revealed a significant main effect for place of
      articulation and a significantly larger difference in FTR between the two places
      of articulation for CWNS than for CWS. Findings suggest that the organization of
      the FTR production for place of articulation may not be as contrastive or refined
      in CWS as in CWNS, a subtle difficulty in the speed of speech-language
      production, which may contribute to the disruption of their speech fluency.

PMID- 12199399
TI  - Interaction of speech coders and atypical speech II: effects on speech quality.
AB  - We investigated how standard speech coders, currently used in modern
      communication systems, affect the quality of the speech of persons who have
      common speech and voice disorders. Three standardized speech coders (GSM 6.10 RPE
      LTP, FS1016 CELP, and FS1015 LPC) and two speech coders based on subband
      processing were evaluated for their performance. Coder effects were assessed by
      measuring the quality of speech samples both before and after processing by the
      speech coders. Speech quality was rated by 10 listeners with normal hearing on 28
      different scales representing pitch and loudness changes, speech rate, laryngeal
      and resonatory dysfunction, and coder-induced distortions. Results showed that
      (a) nine scale items were consistently and reliably rated by the listeners; (b)
      all coders degraded speech quality on these nine scales, with the GSM and CELP
      coders providing the better quality speech; and (c) interactions between coders
      and individual voices did occur on several voice quality scales.

PMID- 12199400
TI  - Self-esteem in children with specific language impairment.
AB  - The purpose of this preliminary study was to probe the self-perceptions of a
      group of children with specific language impairment (SLI) and their typically
      developing peers. A measure of self-esteem was administered to 46 children
      between the ages of 6 and 9 years old and 34 children between the ages 10 and 13.
      In the younger group, there were no statistically significant differences between
      children with SLI and typically developing children in the way they perceived
      themselves across domains of competence and acceptance. In the older group,
      children with SLI perceived themselves more negatively in scholastic competence,
      social acceptance, and behavioral conduct than did children with typical language
      development. Differences were evident in areas that were most affected by
      language impairment.

PMID- 12199401
TI  - Responding to joint attention and language development: a comparison of target
      locations.
AB  - This study examined the importance of target location (within vs. outside the
      visual field) on the relation between responding to joint attention and
      subsequent language development in 47 normally developing infants. The results
      supported a developmental progression in the infants' ability to locate targets
      from within to outside the visual field. In addition, individual differences in
      15-month-old infants' ability to correctly locate targets outside the visual
      field was a unique predictor of expressive language at 24 months. Infants'
      ability to locate targets outside the visual field may demonstrate increasing
      capacities for attention regulation, representational thinking, and social
      cognition that may facilitate language learning. The implications of this study
      are discussed with regard to the usefulness of measures of responding to joint
      attention for identifying early language and developmental delays.

PMID- 12199402
TI  - Profiles of grammatical morphology and sentence imitation in children with
      specific language impairment and Down syndrome.
AB  - The purpose of the present study was to examine the grammatical morphology and
      sentence imitation performance of two different groups of children with language
      impairment and to compare their performance with that of children learning
      language typically. Expressive use of tense-bearing and non-tense-related
      grammatical morphemes was explored. Children with specific language impairment
      (SLI), with Down syndrome (DS), and with typical language development (TL) were
      matched on mean length of utterance (MW). Performance was compared primarily on
      composite measures of tense, tense inflections, and non-tense morphemes, as well
      as on the Sentences subtest of the Wechsler Preschool and Primary Scale of
      Intelligence-Revised (WPPSI-R; D. Wechsler, 1989). Exploratory analyses were
      completed on a set of 11 individual grammatical morphemes as a follow-up to the
      principal analyses. As predicted, the children with SLI performed significantly
      more poorly than the children with TL on all three composite measures. In
      addition, the DS group exhibited significantly weaker performance than did the TL
      group on the tense inflections and non-tense morpheme composites. Although there
      were no statistically reliable differences between the SLI and DS groups on any
      morpheme measure, the groups were not comparably weak in their use of the regular
      post, -ed; the irregular third person singular morphemes (e.g., has, does); the
      present progressive, -ing; or the use of modals. The SLI and DS groups both
      performed more poorly than did the TL group on the sentence imitation task.

PMID- 12199403
TI  - Use of the language development survey (LDS) in a national probability sample of
      children 18 to 35 months old.
AB  - Data are reported from a national probability sample used to norm the Language
      Development Survey (LDS; L. Rescorla, 1989) and the Child Behavior Checklist for
      Ages 1 1/2-5 (CBCL/1 1/25; T. M. Achenbach & L. Rescorla, 2000). Participants
      were 278 children 18 to 35 months old who were highly diverse in socioeconomic
      status (SES), ethnic composition, and language background. Vocabulary scores
      increased markedly with age, were somewhat higher in girls, and were modestly
      correlated with SES. Children of non-Latino White ethnicity had significantly
      higher vocabulary scores and mean length of phrases than children of African
      American or "other" ethnicity (Hispanics/Asians/Native Americans/South
      Asians/mixed), even when SES was used as a covariate. Rate of language delay,
      using the cut-off of fewer than 50 words or no word combinations, was lower in
      the non-Latino White group (4%) than in the other two ethnicity groups (29% and
      24%). Correlations between LDS scores and problem scores on the CBCL/1 1/2-5 were
      low, indicating that language delay and emotional/behavior problems were not
      closely associated in this general population sample of children 18 to 35 months
      old.

PMID- 12199404
TI  - Production operations and the use of nonfinite verbs by children with specific
      language impairment.
AB  - Recent evidence from structural priming studies suggests that children with
      specific language impairment (SLI) are more likely to produce verb morphemes such
      as auxiliary is when their previous sentence contained an auxiliary than when it
      did not. The same paradigm was employed in the present study to determine whether
      failures to include auxiliary is might be due to prior use of nonfinite sentences
      (e.g., The mouse eating the cheese). Preschoolers with SLI and a group of younger
      normally developing children were more likely to produce auxiliary is to describe
      target pictures when the preceding sentence contained auxiliary are than when it
      contained past tense. Use of is in the target sentence was least likely when the
      preceding sentence was nonfinite. The implications of these findings for current
      accounts of SLI and current models of sentence production are discussed.

PMID- 12199405
TI  - Picture naming in early sequential bilinguals: a 1-year follow-up.
AB  - In a previous study, a cross-sectional approach was used to investigate
      developmental changes in basic-level lexical production and cognitive processing
      in early sequential bilinguals, exploring the effects of age and years of
      experience during single-language (Spanish or English) and mixed-language
      (alternating between Spanish and English) picture naming (K. Kohnert, E. Bates, &
      A. E. Hernandez, 1999). The current study reports on the performance, 1 year
      later, of a subgroup of these original study participants (n = 28; mean age =
      10.2 years) on the same experimental task. Overall, from Time 1 to Time 2
      testing, gains were greater in English than in Spanish and in the high
      competition mixed-language processing condition than in the single-language
      processing condition. These results reinforce previous findings of a shift toward
      greater strength in L2 with increasing age (and years of language experience), as
      well as the primary role of cognitive development in control of the dual-language
      system. In addition, examination of individual performance revealed a complex non
      monotonic pattern of L1-L2 change across time within an overall pattern of
      increasing speed, accuracy, and control of the dual-lexical system.

PMID- 12199406
TI  - Changes in hearing-aid benefit following 1 or 2 years of hearing-aid use by older
      adults.
AB  - This study reports the results of a large number of hearing-aid benefit measures
      obtained from 134 elderly hearing-aid wearers during the first year of hearing
      aid usage. Benefit measures were obtained after 1 month, 6 months, and 1 year of
      hearing-aid use by all participants. In addition, follow-up measurements of
      hearing-aid benefit were performed on 49 of these same hearing-aid wearers
      following 2 years of hearing-aid use. All participants in this study were fit
      binaurally with identical full-concha in-the-ear (ITE) hearing aids that used
      linear Class-D amplifiers with output-limiting compression. Benefit measures
      included several objective tests of speech recognition, as well as the subjective
      self-report scales of the Hearing Aid Performance Inventory (HAPI; B. E. Walden,
      M. E. Demorest, & E. L. Hepler) and the Hearing Handicap Inventory for the
      Elderly (HHIE; I. Ventry & B. Weinstein, 1982). Although group means changed only
      slightly over time for all of the benefit measures, significant differences were
      observed for some of the benefit measures, especially among the subjective, self
      report measures of benefit. In almost all of the cases exhibiting significant
      changes, performance was significantly worse (less benefit) at both the 6-month
      and 1-year post-fit interval compared to the measurements at 1 month post-fit. In
      general, the individual data from the 134 participants who were represented in
      the 1-year data set were consistent with the trends in the group data described
      above. Regarding longer term changes in benefit following 2 years of hearing-aid
      use, minimal changes were again observed. In all, there was little evidence for
      acclimatization of hearing-aid benefit in this study in either the group or the
      individual data.

PMID- 12199407
TI  - A comparison of the speech understanding provided by acoustic models of fixed
      channel and channel-picking signal processors for cochlear implants.
AB  - Vowels, consonants, and sentences were processed by two cochlear-implant signal
      processing strategies-a fixed-channel strategy and a channel-picking strategy-and
      the resulting signals were presented to listeners with normal hearing for
      identification. At issue was the number of channels of stimulation needed in each
      strategy to achieve an equivalent level of speech recognition in quiet and in
      noise. In quiet, 8 fixed channels allowed a performance maximum for the most
      difficult stimulus material. A similar level of performance was reached with a 6
      of-20 channel-picking strategy. In noise, 10 fixed channels allowed a performance
      maximum for the most difficult stimulus material. A similar level of performance
      was reached with a 9-of-20 strategy. Both strategies are capable of providing a
      very high level of speech recognition. Choosing between the two strategies may,
      ultimately, depend on issues that are independent of speech recognition-such as
      ease of device programming.

PMID- 12199408
TI  - Short-term auditory memory in children using cochlear implants and its relevance
      to receptive language.
AB  - The aim of this study was to assess auditory sequential, short-term-memory (SSTM)
      performance in young children using cochlear implants (CI group) and to examine
      the relationship of this performance to receptive language performance. Twenty
      four children, 5 to 11 years old, using the Nucleus 22-electrode cochlear
      implant, were tested on a number of auditory and visual tasks of SSTM. The
      auditory memory tasks were designed to minimize the effect of auditory
      discrimination ability. Stimuli were chosen that children with cochlear implants
      could accurately identify with a reaction time similar to that of a control group
      of children with normal hearing (NH group). All children were also assessed on a
      receptive language test and on a nonverbal intelligence scale. As expected,
      children using cochlear implants demonstrated poorer auditory and visual SSTM
      skills than their hearing peers when the stimuli were verbal or were pictures
      that could be readily labeled. They did not differ from their peers with normal
      hearing on tasks where the stimuli were less likely to be verbally encoded. An
      important finding was that the CI group did not appear to have a sequential
      memory deficit specific to the auditory modality. The difference scores (auditory
      minus visual memory performance) for the CI group were not significantly
      different from those for the NH group. SSTM performance accounted for significant
      variance in the receptive language performance of the CI group. However, a
      forward stepwise regression analysis revealed that visual spatial memory (one of
      the subtests of the nonverbal IQ test) was the main predictor of variance in the
      language scores of the children using cochlear implants.

PMID- 12199409
TI  - A comparison of learning curves in natural and synthesized speech comprehension.
AB  - This study examined the effect of listening practice on the ability of young
      adults to comprehend natural speech and DECtalk synthesized speech by having them
      perform a sentence verification task over a 5-day period. Results showed that
      response latencies of participants shortened in a similar fashion to sentences
      presented in both types of speech across the 5-day period, with latencies
      remaining significantly longer in response to DECtalk than to natural speech
      across the days. These results suggest that high-quality synthesized speech, such
      as DECtalk, can be useful in many human factors applications.

PMID- 12199410
TI  - HRT: forever or never?

PMID- 12199411
TI  - Clinical pearls: factors affecting reported contraceptive efficacy rates in
      clinical studies.
AB  - Current combination oral contraceptives (OCs) are among the most popular, safe,
      and effective methods of reversible contraception. There are, however, many
      factors that can affect contraceptive failure rates as reported in clinical
      trials, including subject characteristics, factors related to study methodology
      and data analysis, and publication biases. The variability of these factors among
      clinical trials makes meaningful comparisons of contraceptive efficacy data
      across studies difficult, if not misleading or erroneous. It is even more
      difficult to reconcile the differences between clinical trial efficacy rates and
      everyday use rates; for instance, the National Survey of Family Growth reported
      that the rate of OC failure is close to 8% in the United States, which is higher
      than rates reported in clinical trials. Thus, it is important for the clinician
      to consider the many factors that can influence reporting of contraceptive
      failure rates in clinical trials and be aware of the limitations in
      differentiating OCs on the basis of contraceptive efficacy derived from clinical
      trial data. Furthermore, clinical trial data may not accurately predict
      contraceptive efficacy in everyday use.

PMID- 12199412
TI  - The unspeakable illness: the work-up of female urinary incontinence.
AB  - The work-up for female urinary incontinence--i.e., diagnosis and, perhaps,
      initial therapy-is a rational, multi-step procedure, complicated by the reticence
      of patients concerning their problem (except when the chief complaint is
      interference with sexual relations). The chief causes of incontinence are
      (genuine) stress incontinence and overactive bladder (OABR, although there is a
      continuum between them. Diagnosis begins with a review of symptoms and thorough
      history-taking, followed by testing: a urination diary and in-office neurologic
      and gynecologic tests, preceded by a thorough physical examination including all
      relevant gynecologic and neurologic aspects, the latter centered around S2-4--the
      so-called Q-tip test. If tests are inconclusive, or if medical history is
      suggestive, the patient is referred to a urodynamic laboratory for multi-channel
      urodynamic testing and other tests requiring sophisticated urodynamic equipment.
      Treatment plans include pharmacologic therapy of OAB and surgery, but are often
      less drastic.

PMID- 12199413
TI  - Influence of number of pregnancies and total breast-feeding time on bone mineral
      density.
AB  - OBJECTIVE: To analyze how the number of pregnancies and total breast-feeding time
      influence bone mineral density. METHODS: 50 healthy women aged 35 to 40 years
      were studied. Weight, height, number of term pregnancies, time since last
      pregnancy and breast-feeding time were analyzed. They were divided in three
      groups as follows: I: nulligravidas; II: with term pregnancies, but no breast
      feeding; III: with term pregnancies, with breast-feeding. Bone absorptiometry was
      done on all, at lumbar column and femur. The WHO criteria were used to define
      osteopenia and osteoporosis. Comparison among the groups was done with Student's
      t-test for independent samples, and simple regression analysis was done for
      number of gestations, total breast-feeding time, time since last birth, and T
      score at lumbar column and femur. RESULTS: The women were divided as follows: 15
      in group I, 15 in group II, and 20 in group III. The average age was 37.7 +/- 1.5
      years. No differences were found among the three groups in analyzed variables,
      when comparing bone mineral density, T- and Z-scores in L1-L4 average, femoral
      neck, trochanter, and Ward's triangle. There was no correlation among the number
      of gestations, total breast-feeding time, time since last birth, or T-scores at
      lumbar column and femur. CONCLUSION: The number of pregnancies and breast-feeding
      time do not affect bone mineral density.

PMID- 12199414
TI  - Comparison of bone remodeling indicators in climacteric women.
AB  - OBJECTIVE: The objective was to study the polymorphism of collagen type 1 alpha 1
      (COL1 A1) gene as a genetic marker, the biochemical markers of formation
      (osteocalcin) and bone reabsorption (cross-links of pyridinoline-CTx), bone
      mineral density and bone ultrasonometry compared to bone densitometry (DEXA).
      METHOD: The study included 82 women ranging in age from 45 to 60 years,
      menopausal from 1 to 10 years. Polymorphism of COL1 A1 was assessed by PCR
      (polymerase chain reaction), by the specific allele technique. Bone formation
      markers were studied using an ELISA (Novocalcin and Active Crosslaps). A Hologic
      4500 A QDR (DEXA) densitometer and DBM Sonic 1200 IGEA ultrasonograph were
      employed. RESULTS: The bone reabsorption marker (cross-links of pyridinoline-CTx)
      demonstrated statistically significant negative correlation with bone mineral
      density (lumbar and femoral neck), while the bone formation marker (osteocalcin)
      did not display a correlation with bone mineral density. Bone ultrasonometry
      yielded a statistically significant positive correlation with bone densitometry.
      Collagen type 1 alpha 1 polymorphism was not identified by the technique
      employed. CONCLUSION: The bone reabsorption marker (cross-links of pyridinoline)
      and bone ultrasonometry and densitometry are measurements enabling evaluation of
      bone remodeling.

PMID- 12199415
TI  - Defining the high-risk nature of triplet pregnancies.
AB  - Triplet pregnancies are by nature rare. Assisted reproductive technologies have
      multiplied their rate of occurrence in the last two decades. Whether spontaneous
      or induced, triplet pregnancies present obstetric and neonatal-and then often
      lifelong-medical problems severalfold more often than singletons, or even twins.
      The major cause of problems for triplet gestations stems from preterm delivery
      and low birth weight.

PMID- 12199416
TI  - Acoustic radiation force impulse imaging of in vivo vastus medialis muscle under
      varying isometric load.
AB  - Acoustic Radiation Force Impulse (ARFI) imaging is a method for characterizing
      local variations in tissue mechanical properties. In this method, a single
      ultrasonic transducer array is used to both apply temporally short localized
      radiation forces within tissue and to track the resulting displacements through
      time. Images of tissue displacement immediately after force cessation, maximum
      tissue displacement, the time it takes for the tissue to reach its maximum
      displacement, and the recovery time constant of the tissue are generated from the
      ARFI data sets. The information in each of these images demonstrates good
      agreement with matched B-mode images. The study presented here was designed to
      evaluate the relationship between changes in these ARFI parameters with known
      tissue mechanical properties in vivo. Utilizing a modified Siemens Elegra scanner
      with a 75L40 transducer array, ARFI images of vastus medialis muscle were
      generated in three of the authors under four levels of activation (0, 5.7, 14.5,
      and 23.3 N-m). Four ARFI datasets were acquired for each loading condition. The
      observed trends were that displacement magnitude, the time it took for the tissue
      to reach its maximum displacement, and recovery time constant decreased with
      increasing load (i.e., increasing muscle stiffness). Significant differences were
      observed between load levels and subjects for all parameters (p<0.01). The
      results indicate that ARFI imaging may be capable of quantifying tissue stiffness
      in real-time measurements, although further investigation is required.

PMID- 12199417
TI  - Analysis of an adaptive strain estimation technique in elastography.
AB  - Elastography is based on the estimation of strain due to tissue compression or
      expansion. Conventional elastography involves computing strain as the gradient of
      the displacement (time-delay) estimates between gated pre- and postcompression
      signals. Uniform temporal stretching of the postcompression signals has been used
      to reduce the echo-signal decorrelation noise. However, a uniform stretch of the
      entire postcompression signal is not optimal in the presence of strain contrast
      in the tissue and could result in loss of contrast in the elastogram. This has
      prompted the use of local adaptive stretching techniques. Several adaptive strain
      estimation techniques using wavelets, local stretching and iterative strain
      estimation have been proposed. Yet, a quantitative analysis of the improvement in
      quality of the strain estimates overconventional strain estimation techniques has
      not been reported. We propose a two-stage adaptive strain estimation technique
      and perform a quantitative comparison with the conventional strain estimation
      techniques in elastography. In this technique, initial displacement and strain
      estimates using global stretching are computed, filtered and then used to locally
      shift and stretch the postcompression signal. This is followed by a correlation
      of the shifted and stretched postcompression signal with the precompression
      signal to estimate the local displacements and hence the local strains. As proof
      of principle, this adaptive stretching technique was tested using simulated and
      experimental data.

PMID- 12199419
TI  - Doppler angle estimation of pulsatile flows using AR modeling.
AB  - In quantitative ultrasonic flow measurements, the beam-to-flow angle (i.e.,
      Doppler angle) is an important parameter. An autoregressive (AR) spectral
      analysis technique in combination with the Doppler spectrum broadening effect was
      previously proposed to estimate the Doppler angle. Since only a limited number of
      flow samples are used, real-time two-dimensional Doppler angle estimation is
      possible. The method was validated for laminar flows with constant velocities. In
      clinical applications, the flow pulsation needs to be considered. For pulsatile
      flows, the flow velocity is time-varying and the accuracy of Doppler angle
      estimation may be affected. In this paper, the AR method using only a limited
      number of flow samples was applied to Doppler angle estimation of pulsatile
      flows. The flow samples were properly selected to derive the AR coefficients and
      then more samples were extrapolated based on the AR model. The proposed method
      was verified by both simulations and in vitro experiments. A wide range of
      Doppler angles (from 3o degrees to 78 degrees) and different flow rates were
      considered. The experimental data for the Doppler angle showed that the AR method
      using eight flow samples had an average estimation error of 3.50 degrees compared
      to an average error of 7.08 degrees for the Fast Fourier Transform (FFT) method
      using 64 flow samples. Results indicated that the AR method not only provided
      accurate Doppler angle estimates, but also outperformed the conventional FFT
      method in pulsatile flows. This is because the short data acquisition time is
      less affected by the temporal velocity changes. It is concluded that real-time
      two-dimensional estimation of the Doppler angle is possible using the AR method
      in the presence of pulsatile flows. In addition, Doppler angle estimation with
      turbulent flows is also discussed. Results show that both the AR and FFT methods
      are not adequate due to the spectral broadening effects from the turbulence.

PMID- 12199418
TI  - Guidance of cardiac pacemaker leads using real time 3D ultrasound: feasibility
      studies.
AB  - We investigated the feasibility of the guidance of pacemaker lead implantation
      using the pacemaker lead stylet as an acoustic wave-guide combined with real time
      3D ultrasound imaging. In one approach, with a 2.5 MHz transducer coupled to a
      stylet of a pacemaker lead, we used the stylet as a transmitter to track the
      vibrating tip in a 3D ultrasound scan. In another approach, we connected the
      stylet to a piezoelectric actuator vibrating in the range 0.5-5 kHz so that the
      tip of the stylet was imaged using the color Doppler feature of the real time 3D
      ultrasound scanner. In both approaches, tracking of the isolated stylet showed
      good accuracy. However, neither approach offered sufficient signal-to-noise ratio
      to detect the vibration within the lumen of an intact pacemaker lead.

PMID- 12199420
TI  - An efficient motion estimation and compensation method for ultrasound synthetic
      aperture imaging.
AB  - This paper describes a method for overcoming motion artifacts in synthetic
      aperture imaging. The method is based on a computer simulation study on the
      influence of target motion on synthetic aperture techniques. A region-based
      motion compensation approach is used in which only the axial motion is estimated
      and compensated for a given region of interest under the assumption that the
      whole ROI moves uniformly. The estimated axial motion is calculated with a
      crosscorrelation method at the point where the focused signal has the maximum
      energy within the ROI. We also present a method for estimating axial motion using
      the autocorrelation method that is widely used to estimate average Doppler
      frequency. Both computer simulations and in vivo experiments show that the
      proposed crosscorrelation-based method can greatly improve the spatial resolution
      and SNR of ultrasound imaging by implementing SA techniques for two-way dynamic
      focusing without motion artifacts. In addition, the autocorrelation-based motion
      compensation method provides almost the same results as the crosscorrelation
      based method, but with a dramatically reduced computational complexity.

PMID- 12199421
TI  - Static muscular load, an increasing hazard in modern information technology.

PMID- 12199422
TI  - Effect of mental and physical demands on muscular activity during the use of a
      computer mouse and a keyboard.
AB  - OBJECTIVES: This study explores the effects of mental and physical demands on
      muscular activity in the use of the mouse and keyboard in computer work in a time
      pressed situation. METHODS: Twelve female subjects performed a computer task with
      four combinations of two forms of input device (computer mouse and keyboard) and
      two levels of mental demand (with and without a color word test). The time
      available for response was limited. Performance and electromyography (EMG) were
      recorded for the forearm, shoulder, and neck muscles. RESULTS: The mean static
      muscular activity was 2-7% of the maximum EMG for the forearm and neck extensor
      muscles. All the muscles for which recordings were made showed increased muscular
      activity in the mentally demanding condition. The increase in the static muscular
      activity level varied from 0.3% of the maximum EMG for the right trapezius muscle
      to 2.6% for the extensor carpi ulnaris muscle. Significant differences in
      muscular activity between the use of a computer mouse and a keyboard were only
      found for the neck extensors; in the computer mouse condition there was a static
      EMG level of 3.5% for the maximum EMG, compared with 2.8% for the keyboard.
      CONCLUSIONS: Mental demands during computer work increased muscular activity in
      all of the recorded muscles. Increased muscular activity was found in the neck
      during the use of the mouse in comparison with the use of the keyboard; this
      phenomenon may be related to higher visual demands during the use of a mouse than
      with a keyboard. These findings may help explain the adverse effects of
      psychosocial work factors on the musculoskeletal system.

PMID- 12199423
TI  - High physical and psychosocial load at work and sickness absence due to neck
      pain.
AB  - OBJECTIVES: This study investigates the relationship between physical and
      psychosocial load at work and sickness absence due to neck pain. METHODS: A
      prospective cohort study with a follow-up period of 3 years (1994-1998) was
      performed among a working population. At the beginning of the study, physical
      load at work was quantified by means of video recordings. Work-related
      psychosocial variables were measured by means of the Job Content Questionnaire.
      The frequency of sickness absence due to neck pain with a minimal duration of 3
      days was assessed on the basis of company registrations during the follow-up
      period. Altogether 758 workers were included in the analyses. Possible
      confounding by individual characteristics, physical load, and psychosocial load
      was studied. RESULTS: Work-related neck flexion and neck rotation, low decision
      authority, and medium skill discretion showed statistically significant increased
      risks for sickness absence due to neck pain (adjusted rate ratios ranging from
      1.6 to 4.2). High quantitative job demands, low skill discretion, and low job
      security showed nonsignificant increased risks for sickness absence due to neck
      pain (adjusted rate ratios of 2.0, 1.6 and 1.7, respectively). Work-related
      sitting, conflicting job demands, supervisor support, and co-worker support did
      not increase sickness absence due to neck pain. CONCLUSION: Work-related neck
      flexion, neck rotation, low decision authority, and medium skill discretion are
      risk factors for sickness absence due to neck pain. There are indications that
      high job demands, low skill discretion, and low job security are also risk
      factors for sickness absence due to neck pain.

PMID- 12199424
TI  - Reliability assessment of a coding scheme for the physical risk factors of work
      related musculoskeletal disorders.
AB  - OBJECTIVES: This study assessed the reliability of a novel coding scheme for
      physical risk factors for musculoskeletal disorders reported to an occupational
      surveillance scheme. METHODS: Since 1997 new cases of musculoskeletal disease
      have been reported as part of a surveillance scheme by over 300 consultant
      rheumatologists in the United Kingdom; the rheumatologists also gave a short
      description of the tasks and activities they considered to be causal. With the
      use of a summary of the activities described, a coding scheme was developed
      comprising 16 categories of task codes and another 16 categories of movement
      codes. Four reviewers coded the work activities independently for 576 cases. The
      fourth rater coded the cases twice. With the use of a single summary kappa
      statistic and the matrix of kappa coefficients, both interrater reliability and
      intrarater reliability were assessed. RESULTS: The overall interrater agreement
      on the task codes was good (kappa = 0.73), with the best agreement for keyboard
      work (kappa = 0.96) and the worst for assembly work (kappa = 0.40, kappa = 0.37).
      The interrater agreement on movement codes was also good (kappa = 0.79), with the
      best agreement for kneeling (kappa = 0.94) and the worst for materials handling
      (kappa = 0.10). The intrarater agreement was somewhat better than the interrater
      agreement with both codes. CONCLUSIONS: The results suggest that the coding
      scheme was, on the whole, reliable for classifying the physical risk factors
      reported as causal.

PMID- 12199425
TI  - Job strain and major risk factors for coronary heart disease among employed males
      and females in a Swedish study on work, lipids and fibrinogen.
AB  - OBJECTIVES: The aim of this study was to analyze the relationship of job strain
      (high psychological job demands and low decision latitude) to hypertension, serum
      lipids, and plasmafibrinogen. METHODS: The study population consisted of employed
      persons between the ages of 15 and 64 years in the counties of Stockholm,
      Vasternorrland, and Jamtland, Sweden. The data collection was carried out during
      1992-1998. A total of 10,382 subjects participated in a medical examination and
      completed a questionnaire. RESULTS: No strong associations were found between job
      strain and plasma fibrinogen. The males reporting job strain had lower levels of
      total cholesterol and high-density lipoprotein cholesterol than the other males.
      Similar tendencies were found for the females. The females, but not the males,
      with job strain had an increased prevalence of hypertension when compared with
      the subjects with relaxed psychosocial work characteristics. In the subgroups of
      younger males and females an adverse association between job strain and the ratio
      between low-density and high-density lipoprotein cholesterol was noted.
      CONCLUSIONS: The results do not support the hypothesis that job strain has an
      adverse impact on serum total cholesterol and plasma fibrinogen levels. They
      suggest that an increased risk of coronary heart disease in association with job
      strain, if causal, is mediated by other factors, possibly partly by hypertension
      and low levels of high-density lipoprotein cholesterol.

PMID- 12199426
TI  - Sleep apnea and occupational exposure to solvents.
AB  - OBJECTIVES: The possible effects of exposure to neurotoxic substances such as
      gasoline, diesel fuel, paint, varnish, and solvents on the pathogenesis of
      obstructive sleep apnea were examined. METHODS: Four hundred and forty-three
      persons with incident obstructive sleep apnea were recruited within the framework
      of a case-referent study. A reference population (N=397) was included as the
      first reference group. In addition 106 patients whose sleep laboratory findings
      confirmed that they were not suffering from obstructive sleep apnea were then
      included as a second reference group. Data were gathered with a questionnaire
      which had to be filled out by the persons with obstructive sleep apnea (cases)
      and the referents themselves. In the assessment of occupational exposure the
      questionnaires were filled out by the subjects themselves, and a job-exposure
      matrix was also used. Data were analyzed using logistic regression to control for
      age, region, body mass index, cigarette smoking, and alcohol consumption.
      RESULTS: None of the exposures were statistically significantly associated with
      obstructive sleep apnea. There was no correlation with occupation. Only current
      activities in service occupations revealed an increased odds ratio, 1.6 (95%
      confidence interval 1.1-2.4). CONCLUSIONS: No suggestion was found of an
      association between exposure to solvents and obstructive sleep apnea.

PMID- 12199427
TI  - Airway responses of healthy farmers and nonfarmers to exposure in a swine
      confinement building.
AB  - OBJECTIVES: The objective of the study was to determine whether swine farmers
      continuously exposed to the farming environment react differently to acute
      exposure than previously unexposed nonfarmers. METHODS: Nine healthy nonfarmers,
      not previously exposed to a farming environment, and eight swine farmers were
      exposed in a swine confinement building for 3 hours while weighing pigs. Lung
      function measurements, methacholine challenge tests, and nasal lavages were
      performed before and after the exposure. Blood samples were drawn repeatedly
      during the exposure day. Differential cell counts and cytokine levels were
      analyzed in the nasal lavage fluid and blood. RESULTS: The exposure levels were
      the same in both groups. Bronchial responsiveness to methacholine increased by a
      median of 4.0 (25th-75th percentiles 2.2-10.1 among the nonfarmers) and 0.7 (25th
      75th percentiles 0.01-3.5 among the farmers) doubled concentration steps. The
      median serum levels of interleukin-6 increased from 3.8 (25th-75th percentiles <3
      5.8) ng/l to 23.7 (25th-75th percentiles 11.6-41.6) ng/l among the nonfarmers and
      from <3 to 3.8 (25th-75th percentiles 3.1-11.6) ng/l among the swine farmers
      after the exposure. Swine dust exposure induced a ninefold increase in the total
      cell counts in the nasal lavage fluid of the nonfarmers, but no significant
      increase among the swine farmers. CONCLUSIONS: The exposure altered lung function
      and bronchial responsiveness, as well as cell number and cytokines in blood and
      nasal lavage fluid in previously unexposed nonfarming subjects, whereas only
      minor alterations were found in the farmers. This finding suggests possible
      adaptation mechanisms in chronically exposed swine farmers.

PMID- 12199428
TI  - Occupational exposure to hairdressing chemicals and immunoglobulin E synthesis.
AB  - OBJECTIVE: This study assessed the effect of exposure to hairdressing chemicals
      on total and allergen-specific serum immunoglobulin E (IgE) in hairdressers.
      METHODS: The study was based on a questionnaire sent to 100 hairdressers (91%
      responding) and a reference group of 95 office workers (84% responding). The
      questionnaire sought information on allergy, respiratory symptoms during the past
      year, work conditions (exposure), and smoking habits. The hairdressers were
      divided into two groups, one of high exposure and another of low exposure. Total
      serum IgE and allergen-specific IgE towards the most prevalent airborne allergens
      were analyzed. RESULTS: The serum levels of total IgE were significantly higher
      among the highly exposed hairdressers than among the office workers. The
      prevalence of asthma-like respiratory symptoms during the past year was
      significantly higher among the highly exposed hairdressers than among the office
      workers. The total serum IgE level was significantly higher among the
      hairdressers than among the office workers (101 versus 51 IU/ml blood), but this
      difference disappeared after adjustment for age, atopy, and smoking. A total of
      5.5% of the hairdressers versus none of the office workers had specific serum IgE
      antibodies towards latex. There were no differences in general allergy
      (Phadiatop) among the hairdressers and office workers. CONCLUSIONS: Serum levels
      of total IgE were significantly higher among highly exposed hairdressers than
      among office workers. The relationship could not be completely explained by such
      covariables as age, smoking, or sensitization to latex allergens.

PMID- 12199430
TI  - Occupational dust exposure and the risk of laryngeal cancer in Turkey.
AB  - OBJECTIVES: A hospital-based case-referent study was conducted to identify
      occupational risk factors for laryngeal cancer. In a previous report an
      association was found between laryngeal cancer and occupations with potential
      dust exposure; a job-exposure matrix was developed to aid further evaluation of
      laryngeal cancer risks from five occupational dust exposures. METHODS: Among 7631
      cancer cases from the Okmeydani Hospital, Istanbul, between 1979 and 1984, 958
      larynx cancer cases were identified among men. After exclusions, 940 laryngeal
      cancer cases and 1519 referents were available. A standardized questionnaire was
      used to obtain basic information on the patients. Seven-digit standard
      occupational and industrial codes were created to classify the job and industrial
      titles. A job-exposure matrix was developed for occupational dusts, including
      silica, asbestos, wood, cotton, and grain, and age-, smoking-, and alcohol
      adjusted odds ratios (OR) and 95% confidence intervals (95% CI) were calculated
      to evaluate risks of laryngeal cancer. RESULTS: An excess of laryngeal cancer
      occurred for workers potentially exposed to silica and cotton dust, particularly
      for supraglottic cancer (OR 1.8, 95% CI 1.3-2.3, for silica and OR 1.6, 95% CI
      1.1-2.5, for cotton dust), and there was a significant dose-response relationship
      with silica exposure. No relationship was found between laryngeal cancer and
      asbestos, grain, or wood dust exposures. CONCLUSION: Laryngeal cancer, especially
      supraglottic tumors, is associated with silica and cotton dust exposures in
      Turkey.

PMID- 12199429
TI  - Occupation as a risk factor for uveal melanoma in Germany.
AB  - OBJECTIVE: This study explored occupational risks linked to uveal melanoma.
      METHODS: The analysis pooled data from two case-referent studies (hospital- and
      population-based) conducted in Germany between 1995 and 1998, with incident cases
      matched with several referents by age, gender, and region of residence. The
      subjects were contacted through personal or telephone interviews. Their exposure
      status was based on their occupational history. Dichotomous coding for the main
      task and categorization into different occupational classification systems was
      performed. Altogether of 118 cases and 475 referents were included. Adjusted odds
      ratios were calculated by conditional logistic regression. RESULTS: Relevant
      occupations included food, beverage, and tobacco processors [odds ratio (OR) 4.7,
      95% confidence interval (95% CI) 0.99-22.0] and miners (OR 2.3, 95% CI 0.92-5.99)
      among the men and station, engine and heavy equipment operators and freight
      handlers (OR 2.5, 95% CI 0.94-6.58) and medical, dental, pharmaceutical and
      veterinary workers (OR 2.1, 95% CI 0.71-6.02) among the women according to the
      International Standard Classification of Occupations, whereas, according to the
      European Industrial Classification, the relevant occupations were the food
      industry (OR 3.4, 95% CI 1.08-10.5) and the chemical and pharmaceutical industry
      (OR 2.8, 95% CI 1.01-7.78) among the men and machine production (OR 3.2, 95% CI
      0.96-10.7) and health and veterinary sector (OR 2.4, 95% CI 0.97-5.71) among the
      women. CONCLUSIONS: These analyses support the potential role of occupational
      exposure as a risk factor for uveal melanoma. The findings must be interpreted
      carefully since the exposure was assessed indirectly.

PMID- 12199431
TI  - Effectiveness of treatment with lincomycin hydrochloride and/or vaccination
      against Mycoplasma hyopneumoniae for controlling chronic respiratory disease in a
      herd of pigs.
AB  - A herd of pigs infected with Mycoplasma hyopneumoniae was used in a double-blind
      randomised trial to assess the effectiveness of three control strategies against
      chronic respiratory disease in growing-finishing pigs. One group of 61 pigs
      received 220 ppm lincomycin hydrochloride in the feed from day 71 to day 91, a
      second group was vaccinated against M. hyopneumoniae at four and 28 days of age,
      and a third group received both treatments; a fourth group was left untreated as
      a control. Throughout the nursery-finishing period (day 29 to slaughter) the
      average daily weight gain and feed conversion rate of all the treated groups were
      slightly better than in the controls, but there were no significant differences
      between them. There were no significant differences between the treated groups in
      terms of clinical signs, serology, pathology or mortality, which was very low
      throughout the trial.

PMID- 12199432
TI  - Colour-coded duplex sonography of the testes of dogs.
AB  - Colour-coded duplex sonography was used to examine the testes of 42 dogs whose
      testes were normal on clinical examination. With colour Doppler, the blood flow
      in the supratesticular region could be displayed clearly in 70 per cent of the
      cases, independent of the dog's age, bodyweight, pulse rate and the volume of its
      testes. The marginal artery could be displayed clearly in 56 per cent of the
      cases, and the clarity was correlated with bodyweight (P<0.001), testicular
      volume (P<0.001), and pulse rate (P<0.001). The intratesticular blood flow could
      not be discerned in 42 per cent of the cases. With pulsed Doppler, the mean
      resistive index (RI) in the supratesticular region was 0.57, and the mean
      pulsatility index (PI) was 1.00. In the marginal artery, the mean RI was 0.49,
      and mean PI was 0.78. In the intratesticular arteries, the mean RI was 0.47, and
      the mean PI was 0.75. At all three sites both indices were independent of age,
      bodyweight, pulse rate and testicular volume.

PMID- 12199433
TI  - Evaluation of copper sulphate, formalin and peracetic acid in footbaths for the
      treatment of digital dermatitis in cattle.
AB  - The efficacy of three non-antibiotic products (copper sulphate, formalin and
      peracetic acid) was compared with the efficacy of erythromycin, when the four
      substances were applied in footbaths for the treatment of cows with digital
      dermatitis. The cows were divided into four groups on the basis of their current
      housing and randomly allocated to one of the four treatments. Cattle allocated to
      the non-antibiotic treatments were footbathed daily for seven days, but the
      cattle treated with erythromycin were footbathed for two days only. Complete
      records were obtained for 252 lesions from 169 cows. There were significant
      reductions in the lesion scores of all four groups, but there was no significant
      effect of treatment and no significant interaction between treatment and time.

PMID- 12199434
TI  - Screening semen from koalas (Phascolarctos cinereus) for Chlamydia species by
      PCR.
AB  - Artificial insemination is a valuable method for facilitating genetic exchange
      between captive colonies of koalas (Phascolarctos cinereus) and for the
      maintenance of genetically important remnant populations. However, to reduce
      potential disease transmission, their semen needs to be screened for venereal
      diseases caused by organisms such as Chlamydia species. Semen samples from 11
      koalas, eight of them with clinical signs of cystitis, were examined for the
      presence of Chlamydia by an optimised PCR assay. Chlamydia was detected in semen
      from seven of the 11 animals.

PMID- 12199435
TI  - Tonsillar lesions in white-tailed deer (Odocoileus virginianus) naturally
      infected with Mycobacterium bovis.

PMID- 12199436
TI  - Identification of bovine viral diarrhoea virus 2 in cattle in Slovakia.

PMID- 12199437
TI  - Colic associated with a malformation of the ascending colon in a horse.

PMID- 12199438
TI  - Haemorrhagic fever, oedema and high mortality associated with FCV infection.

PMID- 12199439
TI  - Contagious bovine pleuropneumonia and vaccine strain T1/44.

PMID- 12199440
TI  - RCVS fees for 2003.

PMID- 12199441
TI  - Health and urban poverty.

PMID- 12199442
TI  - Health problems of street children in Eldoret, Kenya.
AB  - BACKGROUND: The street children phenomenon is an increasing problem in most
      cosmopolitan cities of the world including Eldoret, which is a fast growing town.
      With the growth of the town so is the increasing number of street children. It is
      therefore important to have baseline data on their health problems. OBJECTIVE: To
      determine the health problems of street children in Eldoret. DESIGN: A
      prospective and descriptive study. SETTING: Eldoret Town, Kenya. SUBJECTS:
      Eldoret street children aged 5-21 years. Type 1 street children were the "on" the
      street children who spent most of their time on the streets but went home in the
      evenings, type 2 were the "of" the street children who spent all their time in
      the streets and had severed their links with their families and did not have a
      home to go to, type 3 were abandoned children staying in a shelter and type 4
      were normal primary school children. RESULTS: One hundred and ninety one children
      were studied. There were 38, 47, 56 and 50 types 1, 2, 3 and 4 children,
      respectively. The most common symptom was cough (28.9%) while frequent diagnosis
      was upper respiratory tract infection (URTI) (12.1%) followed by skin disease
      (50.9%) as the leading disease category. The common drug of addiction was
      cigarette (37.6%) and none of the school children was taking any drug of
      addiction. The prevalence of disease was 467 per 1000 children. Type 2 street
      children had the highest prevalence of disease (833 per 1000 children). Shelter
      children had the least disease prevalence (474 per 1000). Factors determining
      prevalence of disease were the same as in normal children. The malnutrition rate
      was high with 31.1% and 41.9% of the children being stunted and underweight,
      respectively. Type 3 children had the highest rate of malnutrition with 51.8% and
      64.3% being stunted and underweight. CONCLUSION: Street children have a high
      incidence of childhood diseases. Factors determining occurrence of disease among
      street children are as in normal children. Respiratory and skin diseases were the
      leading causes of morbidity. Drug abuse was rampant among the street children but
      none of the school children abused any drug. Sexually transmitted infections were
      not prevalent. Most of the shelter children were malnourished. RECOMMENDATIONS:
      The government of Kenya should provide free health care for street children in
      public hospitals. Further studies should be carried out on the prevalence of
      sexually transmitted diseases based on laboratory testing and on the causes of
      the injuries suffered by the street children. The reasons for the poor
      nutritional status of the shelter children should be analysed and appropriate
      measures taken.

PMID- 12199443
TI  - Determinants of child mortality in a rural Ugandan community.
AB  - OBJECTIVE: To estimate the rate of and risk factors associated with child
      mortality in rural eastern Uganda. DESIGN: A community based cross-sectional
      study using the preceding birth technique--a robust method of obtaining
      information of survival of the previous child. SETTING: A rural district in
      Eastern Uganda. PARTICIPANTS: In total, 2888 multigravidae were interviewed in
      April and May 1999. MAIN OUTCOME MEASURE: Number of deaths among children born
      alive. RESULTS: The under-two child mortality rate was 108 per 1000 livebirths.
      The annual child mortality was 82 per 1000 child-years of risk. Child mortality
      was associated with low parental education, being born to adolescent mothers or
      mothers aged 35 or more. Unconditional logistic regression showed that children
      born to uneducated parents had a doubled risk of not celebrating their second
      birthday. It was three times more likely for a child to die in the neonatal
      period than in the first year of life. Child mortality risk decreased by 4% and
      6% for every year of education attained by mothers and fathers, respectively.
      Parity, residence and marital status were not associated with excess risk of
      child mortality. Seasonal mortality followed the El Nino rainfall pattern.
      Finally, there were geographical differences in child mortality although this was
      not statistically significant. CONCLUSION: Monitoring trends in child mortality
      at district level can be done using the preceding birth technique in antenatal
      settings. Maternal education, an important predictor of child survival should be
      included in routine data collection at clinics.

PMID- 12199444
TI  - Impact of health care financing reforms on the management of malaria in Ghana.
AB  - OBJECTIVE: To determine the impact of the introduction of the 'cash and carry'
      system on how health care providers manage malaria cases in Ghana. DESIGN: A
      cross sectional study of treatment patterns of cases of malaria. SETTING: Health
      services in Ghana changed significantly in 1992, from being virtually free to a
      'cash and carry' system in which all patients attending government health
      services had to pay in full for drugs and services. Staff of private companies
      and parastatal organisations continue to enjoy free health services at other
      clinics and hospitals. SUBJECTS: Prescriptions for 9539 cases diagnosed as having
      malaria at the out-patient departments (OPD) of eight health facilities four in
      the 'cash and carry' scheme and four outside this scheme were reviewed. RESULTS:
      The mean (SD) number of drugs prescribed per case of malaria was higher for the
      'cash and carry' group than for the 'free for service' group; 4.5+/-1.3 versus
      3.8+/-1.3 (p value <.001). Injection chloroquine was used more frequently in the
      'cash and carry' group than in the 'free service' group 56.4% and 28.6%
      respectively (p value <.001). Second-line antimalarial drugs were however, more
      often used in the 'free service' group 13.5% versus 7.3% (p value <.001). About
      30% of the 'cash and carry' group received antibiotics, compared with 15.5% of
      the 'Free Service' group. Logistic regression analysis showed that the modality
      of payment for services contributed significantly to whether a case of malaria
      was managed with more than three drugs, or received injection chloroquine or
      antibiotics or a non-steroidal anti-inflammatory drug. CONCLUSION: Evidence in
      this study suggests that health care providers tend to pay more attention in
      treating the symptoms of malaria in cases in which patients pay for service. This
      leads to unnecessarily high costs of care for the individual and the health
      system.

PMID- 12199445
TI  - Social support needs and adjustment of cancer patients.
AB  - BACKGROUND: Given the limited health care funds and increasing survival from
      cancer, services should be targeted to meet patients' post-treatment need.
      OBJECTIVES: To identify which of the needs that patients consider important;
      examine how they compare the role of the family, nurses and friends in meeting
      these needs; and assess the relationship between social support and adjustment to
      cancer. SETTING: Radiotherapy clinic, University College Hospital, Ibadan,
      Nigeria. DESIGN: Cross-sectional study. MEASUREMENTS: A 29-item needs
      questionnaire for assessing patients' expressed and perceived informational,
      physical (relief of pain), emotional and instrumental (economic) needs/support
      from family, friends and nurses; and indices of social adjustment (self-esteem,
      coping, acceptance). SUBJECTS: Seventy two (20 males and 52 females) consecutive
      attendees mean age, 41.1, SD 12.7. RESULTS: The highest needs expressed were
      physical (95.8%) and informational (81.7%), while emotional support was the most
      perceived as provided. Nurses and families were similarly perceived as
      significant providers of total social support, with nurses being identified as
      best providers of physical and instrumental support. Over 75% felt socially
      adjusted. Informational support was the most important predictor of social
      adjustment, while total social support predicted self-esteem. CONCLUSION: The
      findings support previous work indicating that clinicians should drop their
      reticence and provide adequate information to cancer patients and their
      relatives. Staff social support is appreciated by patients and is predictive of
      social adjustment. Policy makers should consider social welfare measures to
      relieve the burden of cancer on families.

PMID- 12199446
TI  - Antimicrobial resistance of bacterial organisms isolated from rats.
AB  - OBJECTIVE: To determine if antimicrobial resistance occurs in various bacterial
      species isolated from rats. METHOD: Two hundred and fifteen rats were trapped
      from areas in and around Nairobi, Kenya. They were sacrificed and their
      intestinal, liver and spleen specimens obtained. Various bacterial species were
      isolated from these specimens. The species were analysed for antimicrobial
      susceptibility to 12 commonly used antimicrobials using the disc diffusion
      technique. RESULTS: The bacterial species isolated included pathogenic and
      potentially pathogenic ones such as Escherichia coli 137, Salmonella typhimurium
      1, Klebsiella pneumoniae 2, Enterobacter cloacae 4, Enterobacter sakazakii 2,
      Citrobacter freundii 3, Morganella morganii (2), Pseudomonas aeruginosa 2 and
      Burkhoddria cepacia 6. Depending on the species, the resistance to the various
      antimicrobials were: 0-100% for cefotaxime, nalidixic acid, cefuroxime,
      tetracycline, chloramphenicol, co-amoxyclav, sulfamethoxazole, ampicillin,
      trimethoprim and cephradine, 0-66.6% for gentamicin and 0-25% for apramycin.
      CONCLUSION: The results showed that, rats from the study area harboured bacterial
      species with antimicrobial resistance. These micro-organisms may form an
      important reservoir for antibiotic resistance which could pose a public health
      hazard. Control of rat populations, better management of sewer systems and waste
      dumping sites are recommended in order to reduce occurrence of these drug
      resistance reservoirs.

PMID- 12199447
TI  - Follow up of oesophageal cancer therapy at the Kenyatta National Hospital,
      Nairobi.
AB  - OBJECTIVE: To determine the pattern of follow-up for oesophageal cancer patients
      following hospital discharge and reviewing followup results of the different
      treatment modalities with emphasis on oesophagectomies. DESIGN: A retrospective
      hospital based study covering the period January 1987 to January 2001. SETTING:
      Surgical outpatient clinic, Kenyatta National Hospital, Nairobi. MAIN OUTCOME
      MEASURES: Determination and the comparison of the one, two and three-year
      followup rates for the different treatment modalities and their median follow-up
      period in addition to reviewing the common variables associated with follow-up.
      RESULTS: The median followup for patients managed by oesophagectomy was 9.5
      months with a 43%, 22% and 10% one-, two- and three-year followup rates
      respectively. This compared to a median of two months and a 7% and 3% one-, and
      two- year followup rate for patients managed by intubation, and a 3-month median
      followup with a one- and two- year follow-up rate of 12% and 4% respectively for
      radiotherapy treated patients. Oesophagectomy patients had a better followup
      compared to intubations and radiotherapy (p<.00001). Oesophagectomy for stage T4
      tumours had an apparently better follow-up compared to both stage T1-3 tumours
      and patients managed with intubations (p=.002 and .02 respectively).

PMID- 12199448
TI  - The growing threat of arbovirus transmission and outbreaks in Kenya: a review.
AB  - OBJECTIVE: To review the trend in arbovirus outbreaks and activity in Kenya in
      the last ten years. DATA SOURCE: Published reports of past outbreak
      investigations and more recent data available at the Arbovirology and Viral
      haemorrhagic fevers reference centre, Centre for Virus Research, Nairobi. STUDY
      SELECTION: Past and recent outbreaks and active transmission reports of
      arboviruses of medical importance in Kenya including Yellow fever (YF), Rift
      Valley Fever (RVF), Dengue and Crimean Congo haemorrhagic fever. SYNTHESIS: Each
      of the viruses was reviewed providing critical information on classification,
      incidence, outbreak, and activity in Kenya, mode of transmission, recognition of
      cases, management and control. CONCLUSION: There is increased frequency of
      outbreaks and detection of arbovirus activity in humans and vectors in the last
      ten years including re-emergence of YF virus as a public health concern in Kenya.
      The importance of recognition of cases and diagnosis (especially in malaria
      endemic areas) is critical to management and control. Effective countrywide
      surveillance backed by diagnostic centres is highly recommended.

PMID- 12199449
TI  - Participation of primary school teachers in oral health education in Rungwe
      District, Tanzania.
AB  - BACKGROUND: Tanzanian primary school teachers have long been utilised as oral
      health educators but little is known about their level of participation.
      OBJECTIVES: To asses the participation of primary school teachers as general and
      oral health educators. DESIGN: Cross-sectional, using structured self
      administered questionnaires. SETTING: Rural and urban Primary Schools in Rungwe
      District, Mbeya Tanzania. PARTICIPANTS: Primary school teachers from 15 rural and
      4 urban schools. MAIN OUTCOME VARIABLES: Provision of oral health education.
      RESULTS: Teachers with primary education, who are teaching in lower grades were
      significantly more active in providing general and oral health education (OHE)
      than those with secondary education and who teach pupils in higher grades.
      CONCLUSION: Oral health education seems to be given mainly to primary school
      pupils in lower grades; teachers involved in oral health education provision were
      mainly female juniors in the profession and relatively young by age (below 40
      years old). RECOMMENDATION: There is a need for influencing teachers of pupils in
      higher grades and males to be involved in oral health education programmes
      throughout their teaching profession.

PMID- 12199450
TI  - Major obstetric interventions among encamped refugees and the local population in
      Turkana District, Kenya.
AB  - BACKGROUND: Maternal mortality in developing countries remains high due to lack
      of appropriate emergency obstetric care. Major obstetric intervention (MOI) rate
      can be used as an indicator of unmet obstetric needs and quality of care.
      OBJECTIVES: Identify indications for major obstetric interventions, determine MOI
      rates and assess extent of unmet obstetric need for women in Turkana district,
      Kenya. DESIGN: Descriptive bi-directional study. SETTING: Turkana district:
      Kakuma Refugee Camp, Kakuma Catholic Mission and Lodwar District Hospitals.
      SUBJECTS: Four thousand two hundred and eighty encamped refugee women and 7,630
      women from the host population delivering in Turkana district between January
      1995 and September 1999. DATA SOURCES: Maternity registers, inpatient case notes
      and theatre registers. MAIN OUTCOME MEASURES: Maternal mortality, perinatal
      mortality, major obstetric interventions, unmet obstetric need and length of
      stay. RESULTS: The subjects from the two study populations were similar with
      respect to age, parity and indications for surgical intervention. Caesarean
      section was the only major obstetric intervention. Overall, caesarean section
      rate was significantly higher among refugees than in the host population (3.1%
      versus 2.1%, p<0.01; CI 1.4-2.1). Maternal indications were the main reasons for
      c/s in both populations, with the c/s rate being higher for refugees than for
      local women (2.5% versus 1.7%). At least 0.8% of parturient women from the host
      population had unmet obstetric needs: this translates to 61 pregnant women who
      may have died or experienced birth-related complications over the study period.
      The mean length of hospital stay was much less for refugee women than for the
      host population (8.1 days versus 11.3 days). CONCLUSION: Encamped refugee women
      in Kakuma have better obstetric care than those from the host population, and the
      level of unmet obstetric needs in the district is high. This imbalance could be
      reduced through resource sharing and integration of refugee health care services
      with that for the host population.

PMID- 12199451
TI  - Dietary patterns and dental caries in nursery school children in Nairobi, Kenya.
AB  - OBJECTIVE: To determine the dietary patterns and the prevalence of dental caries
      among nursery school children in Nairobi. DESIGN: A cross-sectional study.
      SETTING: Nursery schools in Nairobi, Kenya. SUBJECTS: Three hundred and four
      nursery school-children (149 males and 155 females) aged 3-5 years were assessed
      in 1997. RESULTS: There was a high consumption of fruits, vegetables and milk on
      a daily basis. There was also a high consumption of snacks both at home and at
      school. About 96% of the children had been breastfed, while 41% had been bottle
      fed. The prevalence of dental caries was high at 63.5% and a mean decayed,
      missing and filled teeth index (dmft) of 2.95, with the d-component comprising
      96% of the total dmft. Only 1.3% of the children had filled teeth. Increasing age
      was the most predictive factor in dental caries. CONCLUSION: The high consumption
      of refined foods and snacks, as well as the high prevalence of dental caries
      raises a strong public health concern. It is recommended that dietary counselling
      and preventive oral health programmes should be initiated and the already
      existing ones strengthened and incorporated in primary healthcare programmes.
      There is also need for policy makers to come up with guidelines on advertisements
      promoting cariogenic snacks.

PMID- 12199452
TI  - Re: Medicine and literature: symposium in Nairobi on health-related fiction.

PMID- 12199453
TI  - Distant metastases from nasopharyngeal carcinoma at Kenyatta National Hospital,
      Nairobi.
AB  - OBJECTIVES: To determine the frequency and site of distant infraclavicular
      metastases of nasopharyngeal carcinoma (NPC), the stage of the primary tumour at
      presentation of metastasis and the histological trends. To determine if there is
      a correlation between the follow-up rate and different metastatic sites. DESIGN:
      A retrospective study. SETTING: Ear nose and throat surgical and radiotherapy
      clinics at Kenyatta National Hospital, Nairobi. SUBJECTS: Case notes,
      radiotherapeutic and laboratory records of patients presenting with NPC between
      January 1981 and December 1990. RESULTS: The frequency of distant NPC metastases
      was 14.6% and 92.3% manifested within 24 months of admission. It was most
      frequent in the males, a younger age group and early T1 disease. Bilaterality of
      the neck nodes had no relevance on metastatic rate. The bone (66.7%) was the most
      common distant metastatic destination followed by the liver (23.2%). Liver
      metastasis was associated with a shorter follow-up period. CONCLUSION: Apart from
      the late presentation of locoregional disease, the findings are similar to
      studies elsewhere. The preponderance of early primary disease in patients with
      distant metastasis need further appraisal as it preliminarily suggests existence
      of specific biological markers that favour metastases. This can only be done
      after recruiting more cases.

PMID- 12199454
TI  - Biochemical and molecular diagnosis of glutaric aciduria type 1 in a black South
      African male child: case report.
AB  - Glutaric aciduria type 1 (GA-1) is an inborn error of metabolism caused by a
      deficiency of the mitochondrial enzyme glutaryl-Co enzyme A dehydrogenase. GA-1
      is not uncommon amongst Caucasians but to the best of our knowledge, it has
      previously not been reported in black African children. We present a case of GA-1
      in a black South African boy who was referred to hospital at the age of five
      years and ten 10 months with dyskinesia and dystonia accompanied by chorea and
      athetosis. Radiological examination revealed enlarged basal cisterns with
      bilateral fluid collection around the sylvian fissures suggestive of GA-1.
      Analysis of urine showed raised levels of glutaric acid at 520 micromol/mmol
      creatinine (normal <2.0), 3-hydroxyglutaric acid at 113 micromol/mmol creatinine
      (normal <3.0) and a low blood carnitine level of 31.5 micromol/l (normal 35-84).
      A definitive diagnosis was reached through DNA analysis which revealed
      homozygosity for an A293T mutation in the glutaryl-Co-enzyme A dehydrogenase
      (GCDH) gene.

PMID- 12199455
TI  - An unusual origin of supernumerary renal arteries: case report.
AB  - Patent left and right supernumerary inferior polar renal arteries were found in a
      dissection room cadaver. Both arteries originated from the left common iliac
      artery. This is an unusual form of origin of these arteries in the presence of an
      apparently normal ascent and position of the two kidneys.

PMID- 12199456
TI  - Lichens as integrating air pollution monitors.
AB  - In this work an attempt to combine the results of lichen mapping with the
      quantitative levels of certain trace elements in Hypogymnia physodes (L.) Nyl.
      collected on a national scale is presented. An Index of Atmospheric Purity (IAP)
      was calculated using a simple method of mapping lichens based on the assessment
      of the cover and frequency of crustose, foliose and fruticose lichens on
      different tree species. For determination of trace elements in lichens k0
      instrumental neutron activation analysis was used. From the IAP results it can be
      concluded that the epiphytic lichen flora look quite poor with more than 70% of
      the territory in the fourth and third classes, which represent highly polluted
      and moderately polluted air. By comparing IAP results with elemental levels in H.
      physodes using multivariate statistical methods it was found that the elemental
      levels do not have a direct negative effect on the diversity of lichens but can
      help in identification of the type of possible pollution sources and their
      origin.

PMID- 12199457
TI  - Biomonitoring of trace element air pollution: principles, possibilities and
      perspectives.
AB  - This paper discusses the biomonitoring of trace element air pollution. Much
      attention is given to both lichens and mosses as the dominant plant species used
      in biomonitoring surveys. Biomonitoring is regarded as a means to assess trace
      element concentrations in aerosols and deposition. This implies that the monitor
      should concentrate the elements of interest and quantitatively reflect its
      elemental ambient conditions. Environmental impact on the biomonitor's behaviour
      is viewed as resulting in changes in the dose-response relationships. The current
      literature is briefly reviewed, for plant's behaviour modelling, for laboratory
      studies on physiological processes responsible for accumulation, retention and
      release, and for field work on quantification of dose-response relationships.
      Monitoring of elemental atmospheric availability is presented as deriving its
      relevance from presumed impact on both ecosystem performance and human health;
      source apportionment is regarded as an important parallel result for purposes of
      emission regulatory management. For source apportionment, the paper argues in
      favor of multi-elemental determinations, supplemented by information on organic
      compounds and elemental chemical forms. Furthermore, the discussion points
      towards more explicit coupling of biomonitoring data to knowledge and databases
      on both emission registration, ecosystem performance and human health. This means
      that multidisciplinary programs should be set up, which accommodate expert inputs
      from biomonitoring, emission control programs, analytical chemistry, ecology, and
      epidemiology.

PMID- 12199458
TI  - Air quality management in Portugal: example of needs and available tools.
AB  - The Framework Directive (FWD) and the proposed Daughter Directives are the newest
      legislative instruments concerning a new political strategy and air quality
      management approach for Europe. Additionally, the member countries of the United
      Nations Economic Commission for Europe have included the concepts of critical
      load and level for planning air pollution abatement strategies and as a base of
      international agreements concerning limitation of the emissions of air
      pollutants. These concepts imply an accurate knowledge about pollutants
      deposition fluxes. The paper describes the main needs and the tools available to
      define a strategy of air quality management in Portugal. Two study cases are
      presented: (1) extensive monitoring plan to assess the impact of an urban
      incinerator plant; and (2) contribution to a methodology to estimate critical
      levels for a coastal region in Portugal. These different approaches allowed
      illustrating the complexity of the implementation of an air pollution management
      strategy.

PMID- 12199459
TI  - Comparison between urban Toronto PM and selected materials: aerosol
      characterization using laser ablation/ionization mass spectrometry (LAMS).
AB  - Laser ablation/ionization mass spectrometry (LAMS) of particulate matter (PM) was
      undertaken on-line in order to extend and contrast PM characterization.
      Qualitative on-line LAMS results for certified materials and Toronto source
      materials demonstrated the versatility and limitations of the technique. The
      observation of organic and inorganic components of certified materials verified
      the proper working condition of the in-house on-line LAMS. Organic and inorganic
      components of Toronto source materials were also observed with the on-line LAMS.
      Common components identified from both types of materials were Na, Al, Ca, Fe,
      and K. Other recognized components were compared with marker elements reported
      for some common PM emission sources. An in-house off-line LAMS was used to
      analyze urban Toronto PM deposited on glass substrates, while the on-line LAMS
      analyzed individual urban Toronto PM particles that were introduced directly into
      the instrument. Scanning electron microscopy (SEM), X-ray spectrometry and
      inductively coupled plasma atomic emission spectrometry (ICP-AES) were used for
      confirmatory purposes. Organic and inorganic components of urban Toronto PM at
      their typical ng/m3 concentrations were successfully observed in mass spectra
      using both off-line LAMS and on-line LAMS. Identified ions unique to each
      analyzed material were compared to identified ions of urban Toronto PM. The
      ability of LAMS to analyze individual respirable PM particles (viz. < 2 microns),
      both for inorganic trace elements and for organic components, greatly extended
      our capability to characterize PM and also to achieve estimates of concentration
      contributions of each material.

PMID- 12199460
TI  - Determination of trace elements and evaluation of their enrichment factors in
      Himalayan lichens.
AB  - Within the framework of the Ev-K2-CNR research program of the Italian National
      Research Council a specific task project has been initiated for the
      identification of trace elements in lichens in remote high altitude areas. This
      is to evaluate the possibility of using lichens as biomonitors of trace elements
      of atmospheric pollution. In this preliminary study, more than 20 elements have
      been determined in some species of lichens collected at different altitudes (from
      1300 to 5000 m) in the region of the Sagarmatha National Park (Nepal). Samples of
      superficial soils were also collected and analyzed to calculate the trace element
      enrichment factors (EF) using scandium as a normalizing element. Most of the
      trace elements were determined by instrumental neutron activation analysis
      (INAA), while lead and cadmium measurements were carried out with electrothermal
      atomic absorption spectroscopy (ET-AAS). The EF values as well as the elemental
      concentrations are reported and discussed.

PMID- 12199461
TI  - The potential of lichens as long-term biomonitors of natural and artificial
      radionuclides.
AB  - Lichens were used as biomonitors of Chernobyl fallout 137Cs, of cosmogenic 7Be
      and of radioactive members of the natural uranium and thorium decay chains.
      Samples were taken from two locations in France, including lichens sampled at
      different distances of a coal fired power plant and close to a uranium ore
      processing waste disposal site. All samples were analyzed gamma-spectrometrically
      after equilibrium concentrations of short-lived isotopes had been attained.
      Activity concentrations of the members of the uranium and thorium decay chains in
      Parmelia sulcata sampled 1994 decrease with distance from the plant, whereas in
      lichens taken at the waste disposal site a decrease with time was observed.
      Comparison of 7Be activity concentrations measured in lichens with atmospheric
      deposition rates confirms that P. sulcata can be used as a quantitative
      biomonitor of radioactive trace substances. Retention half-lives calculated with
      a simple one-compartment model are 2.6 +/- 1.2 years for cesium, which was
      detected in all samples even more than a decade after the Chernobyl accident, and
      of 0.7 (+/- 0.1) to 3.3 (+/- 0.7) years for lead. Consequences of our results for
      model identifiability and parameter estimation of a two-compartment model are
      discussed.

PMID- 12199462
TI  - Translocation studies of 137Cs and 90Sr in bean plants (Phaseolus vulgaris):
      simulation of fallout.
AB  - In case of an accident at a nuclear power plant with liberation of radioactive
      material into the atmosphere, knowledge about the behavior of plant species when
      in contact with radionuclides is indispensable for safety reasons. The leaf-fruit
      translocation is an important route through which agricultural products are
      contaminated by radionuclides. To quantify the leaf-fruit translocation factors
      for 137Cs and 90Sr in common beans (Phaseolus vulgaris) an experiment was carried
      out in a greenhouse with a randomized block design. 137Cs activity was determined
      by gamma-ray spectrometry, while chemical separation followed by beta counting of
      90Y was used for 90Sr determination. The model applied for translocation
      indicated functional dependence between the moment of tracer application and the
      physiological development of the bean plant. Translocation factors obtained for
      137Cs and 90Sr were 0.16 and less than 0.005, respectively.

PMID- 12199463
TI  - Biomonitoring trace element atmospheric deposition using lichens in China.
AB  - Concentrations of 32 elements, Ag, As, Au, Ba, Ca, Ce, Co, Cr, Cs, Eu, Fe, Hf, K,
      La, Lu, Mo, Na, Nd, Ni, Rb, Sb, Sc, Se, Sm, Sr, Ta, Tb, Th, U, W, Yb, and Zn were
      determined by instrumental neutron activation analysis (INAA) in the early
      preserved epiphytic lichens (Parmotrema recticulatum) from the remote
      southwestern China area in the 1960s, 1980s and 1990s. The concentrations of Ag,
      As, Ce, Cr, Cs, Eu, Fe, Hf, La, Nd, Ni, Sc, Se, Sm, Tb, U, Yb and Zn were dropped
      down by the temporal prolongation. The elemental concentration levels obtained
      from the organisms indicate that the extent of heavy metal atmospheric deposition
      among the sampling sites has been declining during the past decades.

PMID- 12199464
TI  - A European survey of atmospheric heavy metal deposition in 2000-2001.
AB  - The background, administration and current status of the monitoring programme
      "European Survey of Atmospheric Heavy Metal Deposition" is described. All
      European states are invited to join the survey 2000-2001. The co-ordination and
      responsibility for the survey will gradually be transferred from the Nordic
      Council of Ministers to the International Cooperative Programme on Effects of Air
      Pollution on Natural Vegetation and Crops (ICP Vegetation).

PMID- 12199465
TI  - The Biological System of the Elements (BSE)--a brief introduction into historical
      and applied aspects with special reference on "ecotoxicological identity cards"
      for different element species (e.g. As and Sn).
AB  - There are different methods to estimate and predict effects of chemical elements
      and corresponding speciation forms in biochemistry and toxicology, including
      statements on essentiality and antagonisms. Two approaches are given here: (1)
      "identity cards" describing biologically fundamental aspects of element chemistry
      and (2) qualitative discussions which assume the existence of (indirect ways
      into) chemical autocatalysis to be essential for maintaining life and permitting
      reproduction. The latter method, developed by the present authors, draws upon
      Stoichiometric Network Analysis, a safe procedure for complexity reduction in
      feedback networks) and provides estimates of concentration regimes for different
      elements suitable for survival and reproduction. The biochemical hierarchy level
      considered here is that of (metallo-)proteins. Thermodynamic toxicity aspects are
      given in correlations with DMSO solvent affinities and thiocyanate bonding modes.
      Effects of antagonists and of ion substitution within metalloenzymes or of
      metabolic simplification can be dealt with, likewise increased sensitivities
      within symbiotic relationships and within carcinomas are explained which are
      relevant for environmental monitoring and tumour therapy, respectively.

PMID- 12199466
TI  - Internationally harmonized approach to biomonitoring trace element atmospheric
      deposition.
AB  - The International Atomic Energy Agency (IAEA) has been systematically supporting
      work on biomonitoring air pollution using plants since 1997. Such studies are
      presently being supported by the IAEA in 14 countries within a co-ordinated
      research project. The main emphasis of this project is on (1) identification of
      suitable biomonitors of atmospheric pollution for local and/or regional
      application, and (2) their validation for general environmental monitoring,
      whenever possible. Although the participants are using different plants as
      biomonitors in their research in geographically and climatically diverse parts of
      the world, they are harmonising sampling approaches and analytical procedures. In
      this paper, an overview of these activities is given, along with the details,
      where possible. In all of these activities, proficiency testing and analytical
      quality assurance are important issues, which merit special attention. Within the
      scope of an intercomparison exercise, two lichen materials were distributed among
      the participating laboratories and a proficiency test was organised. The results
      obtained proved satisfactory performance for most participating laboratories.

PMID- 12199468
TI  - Atmospheric quality and distribution of heavy metals in Argentina employing
      Tillandsia capillaris as a biomonitor.
AB  - The atmospheric quality and distribution of heavy metals were evaluated
      throughout a wide region of Argentina. In addition, the biomonitor performance of
      Tillandsia capillaris Ruiz & Pav. f. capillaris was studied in relation to the
      accumulation of heavy metals and to its physiologic response to air pollutants. A
      sampling area of 50,000 km2 was selected in the central region of the Argentine
      Republic. This area was subdivided into grids of 25 x 25 km. Pools of T.
      capillaris, where present, were collected at each intersection point. From each
      pool three sub-samples were analyzed independently. Furthermore, five replicates
      were collected at 20% of the points in order to analyze the variability within
      the site. The content of Co, Cu, Fe, Ni, Mn, Pb and Zn was determined by Atomic
      Absorption Spectrometry. Chemical-physiological parameters were also determined
      to detect symptoms of foliar damage. Chlorophylls, phaeophytins, hydroperoxy
      conjugated dienes, malondialdehyde and sulfur were quantified in T. capillaris.
      Some of these parameters were used to calculate a foliar damage index. Data sets
      were evaluated by one-way ANOVA, correlation analysis, principal component
      analysis and mapping. Geographical distribution patterns were obtained for the
      different metals reflecting the contribution of natural and anthropogenic
      emission sources. According to our results it can be inferred that Fe, Mn and Co
      probably originated in the soil. For Pb, the highest values were found in the
      mountainous area, which can be attributed to the presence of Pb in the granitic
      rocks. Ni showed mainly an anthropogenic origin, with higher values found in
      places next to industrial centers. For Zn the highest values were in areas of
      agricultural development. The same was observed for Cu, whose presence could be
      related to the employment of pesticides. The foliar damage index distribution map
      showed that the central and southeastern zones were the ones where the major
      damage in the bioindicator was found. The central zone coincides with the city of
      Cordoba whereas the southeastern area is strictly agricultural, so the high
      values found there could be related to the use of pesticides.

PMID- 12199467
TI  - Biological fluxes conversion and SXRF experiment with a new active biomonitoring
      tool for atmospheric metals and trace element deposition.
AB  - A new active biomonitoring tool, keeping alive mosses for 2 months, had
      demonstrated the buffering action of the water presence on the biological
      activity of three moss species (chlorophyll fluorescence induction method on
      Pleurozium schreberi, Scleropodium purum, Eurhynchium praelongum). The two more
      resistant mosses were exposed on four different sites with parallel exposure of
      monthly bulk collectors during three successive periods of 2 months. The coarse
      and sedimentable particles of bulk collectors were separated into different size
      classes (> 1 mm; 1000-200 microm; 200-40 microm; 40-20 microm). Dry depositions
      and mosses were analysed by Inductively Coupled Plasma Mass Spectrometry (ICP-MS)
      for a stock (microg g(-1)- fluxes (microg m(-2) t(-1)) conversion. The "moss
      plate" allowed relative site (Ba, Cs, Sb, Sr, U) and species (Pb, Sb, Ti, V)
      comparisons. Two months were enough for a significant enrichment (Ba, Cd, Pb, Sb,
      Ti, U, V). Good explicative models were elaborated for Ba, Pb, Sb and Ti (r2 >
      70%) including categorical (sites, moss species) and quantitative variables
      (fluxes of particles size classes). Entire and intact shoots of Scleropodium
      purum were analysed by detected synchrotron radiation induced X-ray fluorescence
      (SXRF). The in vivo distribution of the multi-elemental short term enrichment
      along the moss stem was mainly localized in the plant older parts (Pb, Ti, Cl,
      Se).

PMID- 12199469
TI  - Development and calibration of epiphytic lichens as saltfall biomonitors--dry
      deposition modelling.
AB  - Lichen transplants (Ramalina calicaris and Usnea spp.) were investigated as
      biomonitors of the atmospheric deposition of marine salt, and a calibration model
      was set up to predict the dry deposition of saline elements from the
      concentration of salt tracers in lichens. The study was performed in the
      Portuguese Atlantic coast, where a monthly transplantation program was run in two
      stations that show clear differences in terms of precipitation regimes. At both
      stations, dry deposition and precipitation records were kept for the whole
      duration of the program. General trends in results have indicated that rainwater
      may wash saline elements out of lichens, though such an effect does not appear to
      be linear. A multiple-regression approach was taken to look for a calibration
      between dry-deposition fluxes and lichen concentrations through a stepwise
      technique. The calibration model for data obtained in both stations features two
      break points that define precipitation ranges for low, moderate and heavy rain
      conditions. The results show that lichens can really be used to indicate the dry
      deposition of sea salt.

PMID- 12199470
TI  - An evaluation of olive-tree bark for the biological monitoring of airborne trace
      elements at ground level.
AB  - There is a need to start looking into the possibility of tree bark for
      biomonitoring. Bark from olive trees (Olea europaea Linn.) has been collected
      over an area in northwestern Portugal, featuring a blend of rural lands,
      industrial towns and coastal environments. Samples were analysed through INAA and
      PIXE for their elemental contents. Results from both techniques were reconciled
      and then compared with an extensive database on 46 trace elements in Parmelia
      spp. thalli from the same sites and mostly from the very bark substrates.
      Distribution-free, nonparametric statistics show that, despite signal magnitude,
      variation patterns of bark and lichen concentrations follow one another in a most
      significant way. Selected elements in bark also correlate to a superior extent.
      As far as this investigation goes, there is no reason whatsoever for discarding
      bark as an alternative to lower epiphytes.

PMID- 12199472
TI  - A comparative study for results obtained using biomonitors and PM10 collectors in
      Sado Estuary.
AB  - In 1996 a program was started, financed by the Environmental Ministry of Portugal
      and IAEA, aiming to study the inorganic atmospheric pollutant dispersion in Sado
      Estuary. Gent PM10 air samplers were used for air particulate matter sampling.
      Three sampling sites were chosen, forming a triangle around the fuel power
      station of Setubal. Transplants of Parmelia sulcata Taylor were suspended in
      nylon bags within a rectangle 15 km wide and 25 km long on a 2.5 x 2.5 km grid.
      Two sets of four transplants were hung in each of the 47 locations, one set
      facing the wind and the other set opposing the wind. The transplants were
      suspended in December 1997 for a 1-year period; every 3 months, one transplant of
      each set was collected. Both lichen transplants and PM10 filters were analysed by
      INAA and PIXE. A comparative study of results obtained for the two sampling
      procedures is presented in this work.

PMID- 12199471
TI  - Calibration of lichen transplants considering faint memory effects.
AB  - Biomonitoring, among other purposes, can be used as a tool to study the
      dispersion of trace elements through the atmosphere and back to the earth's
      surface again. In this sense it has been used for more than 20 years now. Yet,
      the calibration of biomonitors elemental contents against other atmospheric
      element dispersion variables like deposition or airborne concentration is still
      an open subject. The knowledge of a calibration nevertheless represents a
      qualitative improvement upon the use of biomonitors. Biomonitors elemental
      contents are usually assumed to depend in a linear way on the average values of
      atmospheric element dispersion variables, thus a linear regression is assumed to
      provide a good calibration. In this work: the element dispersion variables like
      deposition or airborne concentration will be referred in general as availability
      variables due to reasons that will be clarified; an uptake experiment using
      transplants of lichen Parmelia sulcata carried out in Portugal during a 2-year
      period (1994/1996) is described; and new concepts and calibration methods are
      presented. Lichen and aerosol samples were analysed by nuclear analytical
      techniques PIXE and INAA, and total deposition dry residue samples were analysed
      by ICP-MS. A database of roughly 70,000 values was thus created and biomonitor
      calibration carried out considering that biomonitors are not mechanical
      instruments but that they rather describe their exposure with a non-perfect
      memory. Data shows that surveying lichens four times within 1 year, with a period
      of 3 months in between sampling campaigns, allows the recovery of availability
      mean, maxima and standard deviation for many elements.

PMID- 12199473
TI  - Disability as difference.

PMID- 12199474
TI  - Varying degrees confuse the public and reduce credibility.

PMID- 12199475
TI  - Nursing students with learning disabilities.
AB  - Children with learning disabilities grow up to be adults with learning
      disabilities, who may go to nursing school. Nurse educators currently are faced
      with the same challenges as primary and secondary school teachers in meeting the
      education needs of individuals with learning disabilities. It is essential for
      nurse educators to be knowledgeable about learning disabilities, to understand
      the issues involved, and to use appropriate interventions to help these students
      succeed.

PMID- 12199476
TI  - Violence-related content in the nursing curriculum: a follow-up national survey.
AB  - Appropriate educational preparation about violence prevention, assessment, and
      treatment provides critical knowledge and skills that enable nurses to provide
      competent care to violence survivors. This follow-up national survey examined
      changes in the extent, placement, and faculty responsible for violence-related
      content in baccalaureate nursing curricula since the original 1995 survey was
      conducted. This national study used a 31-item mailed questionnaire that requested
      demographic information; data related to course content, clinical experiences,
      curriculum and faculty development, and curriculum evaluation; and
      recommendations. Usable questionnaires were returned from 395 (61%) of 648
      programs surveyed. Findings indicated content related to women, children, and
      suicide and self-destructive behavior was taught primarily in 2 to 4 hours; 46%
      of schools presented sexual and elder abuse content in 1 hour or in readings
      only; and related clinical experiences were primarily coincidental. The majority
      of schools (63%) reported no violence-related faculty development activities
      during the past 4 years despite previous indication of need. More than two thirds
      of programs (68%) did not systematically evaluate violence content, and 75% had
      not developed violence-focused student competencies. Although small gains were
      found in hours of presentation in some content, little has changed in the nursing
      curriculum overall. The significance of this study is related to the relevance of
      nursing education to preparing students and faculty to address the social and
      health problems of increasing violence and abuse.

PMID- 12199477
TI  - The Americans with Disabilities Act: effect on student admission and retention
      practices in California nursing schools.

PMID- 12199478
TI  - SIDS education in nursing and medical schools in the United States.
AB  - This study suggests there is a need to support the efforts already present to
      include SIDS in medical and nursing school curricula. Both programs have
      indicated a need for audiovisual and printed teaching materials. Consideration
      should be given to teaching materials that are easily updated such as computer
      generated materials because of the many rapid changes that take place in SIDS
      research. Currently, textbooks are the most common source of educational material
      used by students. Textbooks could be supplemented with information from recent
      journals and current Web sites. Facilitation of clinical contact with families
      affected by SIDS is important. The availability of local SIDS resources should be
      stressed to both medical and nursing programs as well as opportunities for
      nursing student involvement in the activities of SIDS organizations. While
      lectures are often the only feasible way to deliver SIDS content to large groups
      of students, interactive teaching strategies and involvement with bereaved
      families probably would increase learning beyond the basic level. Nursing schools
      as well as medical schools, confronted with the realities of decreased faculty
      time and budgets, face major challenges in developing case-based curricula that
      prepare students for the next century (Zimmerman et al., 1997). To address these
      needs, curriculum notes were developed by the Education Working Party of the SIDS
      Global Strategy Task Force under the direction of Professor John C. Vance and
      printed in February 1998. The curriculum is divided into seven modules that
      include content and questions as well as references on a variety of issues. A
      problem-based learning package is included and is becoming increasingly popular
      as a teaching strategy (Amos & White, 1998; David & Patel, 1995). There is one
      case each for medical and nursing students in the curriculum package. This
      curriculum can be accessed at www. sidsaustralia.org.au. Other useful Web sites
      include: www.sidsalliance.org. The SIDS Alliance Web site provides support to
      families and information about SIDS. www.sidscenter.org. The National SIDS
      Resource Center Web site provides information and technical assistance for
      parents and professionals on SIDS and related topics. www.aap.org. The American
      Academy of Pediatrics Web site provides guidelines on sleep position and infant
      sleeping environment. www.asipl.org. The Association of SIDS and Infant Mortality
      Programs Web site includes publications and position papers. Finally, many states
      have SIDS services provided by professional programs and parent organizations.
      Students have the opportunity to work with these organizations to provide
      bereavement services and risk-reduction education. The organizations listed above
      can be contacted for further information.

PMID- 12199479
TI  - Students' perceptions of change.

PMID- 12199480
TI  - Violence in society: nursing faculty respond to a health care epidemic.

PMID- 12199481
TI  - Nursing ethics and legal issues: an integrative approach in nursing education.

PMID- 12199482
TI  - A pilot study of teaching clinical decision making with the clinical educator
      model.

PMID- 12199483
TI  - Teaching nursing research using large data sets.

PMID- 12199484
TI  - A critical analysis of homicidal violence.

PMID- 12199485
TI  - Raising the profile of chronic obstructive pulmonary disease with healthcare
      decision-makers.

PMID- 12199486
TI  - Guidelines for the management of chronic obstructive pulmonary disease.
AB  - Chronic obstructive pulmonary disease (COPD) is a respiratory condition
      characterized by progressive decline in lung function. It imposes a considerable
      burden on patients, healthcare services and society that is likely to increase in
      the future. It is, therefore, important to ensure that this disease is managed as
      effectively as possible. In many therapeutic areas, management guidelines have
      been developed in an attempt to ensure that physicians are aware of optimal
      disease management and cost-effective use of healthcare resources. Such
      guidelines are usually prepared by consensus among clinical experts or following
      a systematic review of the evidence. However, there are a number of barriers to
      the implementation of treatment guidelines, including the sheer weight of
      guidelines in all therapeutic areas, a focus on scientific knowledge rather than
      on clinical practice, lack of trust in the recommendations, practical
      considerations (e.g. time, resources, budget) and failure to include the
      perspective of patients. The management guidelines most likely to be implemented
      are those that are quick and easy to use, relevant to the user's practice and
      from a credible source. In COPD, over 40 guidelines have been developed, mainly
      by local respiratory societies as a result of local expert consensus. The
      guidelines developed by the Global Initiative for Chronic Obstructive Lung
      Disease (GOLD) are evidence-based and have the backing of international experts.
      Local implementation plans have been developed to help ensure that GOLD
      recommendations are implemented in practice. In all COPD guidelines, however,
      lung function measures feature prominently with limited reference to outcome
      measures of interest to patients and healthcare payers (e.g. frequency of
      exacerbations requiring hospitalization). Low expectations among physicians and
      patients may also impair implementation. In conclusion, guidelines may improve
      the management of COPD, but the main challenge is to ensure implementation.

PMID- 12199487
TI  - Measuring the success of treatment for chronic obstructive pulmonary disease-
      patient, physician and healthcare payer perspectives.
AB  - The success of treatments for chronic obstructive pulmonary disease (COPD) is
      evaluated by measuring the impact on a range of health outcomes. However, outcome
      measures differ in their relative importance to the various stakeholder groups.
      Patients are most interested in the impact on quality of life and on mortality,
      while physicians also value information about the effect of treatments on lung
      function and disease progression. In contrast to patients and physicians,
      healthcare payers take a population perspective, and need to balance the health
      gains achieved and the costs of treatment. If the management of COPD is to be
      improved, it is important, first, to understand the outcomes of importance to
      each relevant stakeholder group, and then second, to refocus the measures in
      terms that all stakeholders can value.

PMID- 12199488
TI  - Obtaining evidence for use by healthcare payers on the success of chronic
      obstructive pulmonary disease management.
AB  - Healthcare payers make decisions on funding for treatments for diseases, such as
      chronic obstructive pulmonary disease (COPD), on a population level, so require
      evidence of treatment success in appropriate populations, using usual routine
      care as the comparison for alternative management approaches. Such health
      outcomes evidence can be obtained from a number of sources. The 'gold standard'
      method for obtaining evidence of treatment success is usually taken as the
      randomized controlled prospective clinical trial. Yet the value of such studies
      in providing evidence for decision-makers can be questioned due to the restricted
      entry criteria limiting the ability to generalize to real life populations,
      narrow focus on individual parameters, use of placebo for comparison rather than
      usual therapy and unrealistic intense monitoring of patients. Evidence obtained
      from retrospective and observational studies can supplement that from randomized
      clinical trials, providing that care is taken to guard against bias and
      confounders. However, very large numbers of patients must be investigated if
      small differences between drugs and treatment approaches are to be detected.
      Administrative databases from healthcare systems provide an opportunity to obtain
      observational data on large numbers of patients. Such databases have shown that
      high healthcare costs in patients with COPD are associated with co-morbid
      conditions and current smoking status. Analysis of an administrative database has
      also shown that elderly patients with COPD who received inhaled corticosteroids
      within 90 days of discharge from hospital had 24% fewer repeat hospitalizations
      for COPD and were 29% less likely to die during the 1-year follow-up period. In
      conclusion, there are a number of sources of meaningful evidence of the health
      outcomes arising from different therapeutic approaches that should be of value to
      healthcare payers making decisions on resource allocation.

PMID- 12199489
TI  - The burden of chronic obstructive pulmonary disease.
AB  - Chronic obstructive pulmonary disease (COPD) is a disease state characterized by
      chronic airflow limitation that is not fully reversible, with a precise
      definition varying between different management guidelines. The burden of COPD is
      considerable from all relevant viewpoints. From the perspective of society, the
      mortality is already considerable, and it is likely to increase from the sixth to
      the third most common cause of death worldwide by 2020. From the patient's
      perspective, COPD is responsible for disability that restricts many everyday
      activities, such as walking up stairs. The burden of COPD on physicians includes
      increasing consultations for the condition. From the perspective of healthcare
      payers, COPD represents an increasing burden, primarily due to the costs incurred
      when exacerbations require hospital treatment. Despite this considerable burden,
      there are many signs that the impact of COPD is not recognized. Research on COPD
      is currently underfunded in relation to the impact of the disease; patients only
      present late with symptoms; physicians may fail to diagnose the condition and
      healthcare payers may be failing to support treatment approaches that could
      reduce the number of costly hospital exacerbations. Reasons for this overall poor
      recognition of the burden of COPD include lack of recognition of the disease,
      difficulties in diagnosis, poor knowledge of COPD and nihilistic attitudes
      towards the condition and its treatment. Awareness of COPD could be improved with
      education of the public and healthcare professionals. Long-term epidemiological
      studies showing the impact on morbidity and mortality of different treatment
      approaches would also influence the setting of priorities by healthcare payers.

PMID- 12199490
TI  - Decision-making by healthcare payers.
AB  - Healthcare payers are faced with the need to allocate finite resources to
      maximize population health. To assist in decision-making, healthcare payers are
      increasingly using health outcomes information and economic analyses. Healthcare
      payers are often under pressure to make early decisions (around the time of
      product launch), when the evidence available is imperfect. They must also
      consider the equitable distribution of resources between therapeutic areas. Tools
      to help healthcare payers reach transparent and objective decisions include cost
      utility analysis and decision modelling. In practice, healthcare payers in
      different countries (for example, Ireland, France and Canada) vary in the
      approaches taken to reimbursement and formulary listing decisions. The key to
      decision-making among healthcare payers is the provision of appropriate evidence,
      comparing any new treatment approach to current best practice, in situations
      corresponding to real life. When data assumptions have to be made, these should
      be clearly stated with consideration of the impact of varying the assumptions.
      The impact on budgets should also be considered.

PMID- 12199491
TI  - Practical options for estimating cost of hospital inpatient stays.
AB  - Analysts often estimate the cost of hospital services by applying cost/charge
      (c/c) ratios from federal or state data sources to the charges provided on
      hospital discharge records. Recently, a number of sources of discharge data are
      not permitting the release of hospital identities. This study compares several
      sources of c/c data for use in the restricted environment. Accounting data from
      four state systems and from files of the federal Centers for Medicare and
      Medicaid Services (formerly HCFA) are employed. In one analysis hospitals are
      grouped by selected characteristics. C/c varies by state and characteristics.
      Some HCFA and state measures track each other closely. A wider analysis of
      hospital-specific data for 51 states offers a separate test and extension of the
      initial results. The study supports a practical policy option of releasing
      grouped c/c ratios attached to discharge records when identity must be masked.
      Key words: hospital cost, cost to charge ratios, privacy protections.

PMID- 12199492
TI  - Hospital nurse productivity.
AB  - Nurse staffing patterns have come under increased scrutiny as hospital managers
      attempt to control costs without harming service quality or staff morale. This
      study presents production function results from a study of nurse output during
      the period 1997-2000. The results suggest that productivity varies widely among
      hospitals as a function of staffing patterns, methods of organization, and the
      degree of reliance on nurse extender (NE) technicians. NEs can enhance the
      marginal value product of the most educated nurses as the registered nurses (RNs)
      concentrate their workday around patient care activities. The results suggest
      that nurse extenders free RNs from the burden of nonnursing tasks.

PMID- 12199493
TI  - Organizational rationality, performance, and social responsibility: results from
      the hospital industry.
AB  - Drawing on stakeholder theory and Weber's distinction between formal and
      substantive rationality, we posit that: (1) for-profit organizations manage
      stakeholders in ways that result in the organization being more efficient and
      less socially responsible than organizations that are not as profit oriented, and
      (2) organizations with major corporate relationships that are not local manage
      stakeholders in a manner that results in the organization being more efficient
      and less socially responsible than organizations without such arrangements. We
      test these hypotheses with 1994 data on 4,705 of the nation's short-term general
      hospitals using two measures of hospital efficiency and four measures of social
      responsibility. Results confirm that for-profit hospitals and hospitals lacking
      local ties are managing stakeholder relationships in ways that increases the
      efficiency of these hospitals but decreases their social responsiveness. We
      conclude by speculating that organizational efficiency and social responsibility
      may be inversely related and then summarize some of the academic, managerial, and
      policy implications, with emphasis on the implications for stakeholder theory.

PMID- 12199495
TI  - Allocating physicians' overhead costs to services: an econometric/accounting
      activity based-approach.
AB  - Using the optimizing properties of econometric analysis, this study analyzes how
      physician overhead costs (OC) can be allocated to multiple activities to maximize
      precision in reimbursing the costs of services. Drawing on work by Leibenstein
      and Friedman, the analysis also shows that allocating OC to multiple activities
      unbiased by revenue requires controlling for revenue when making the estimates.
      Further econometric analysis shows that it is possible to save about 10 percent
      of OC by paying only for those that are necessary.

PMID- 12199494
TI  - Pharmacy benefit management contracting: an assessment from a recent public
      sector procurement experience.
AB  - In order to contain the cost of pharmaceuticals while preserving access to
      medically necessary drugs, Georgia state government competitively selected a
      single vendor in May of 2000 to manage combined pharmacy benefits under all of
      the state's health programs. By initiating this procedure, it intended to
      maximize the state's purchasing power and improve efficiency while streamlining
      the administrative structure. Synthesizing information from the request for
      proposal (RFP) and technical proposals submitted by 11 pharmacy benefit managers
      (PBMs) in response, we describe a model of public sector PBM contracting approach
      and present an assessment of the industry's service capability and performance
      statistics. Payers who have been using PBM services may find it interesting to
      compare their experience with the recent Georgia experience. Those who are
      considering contracting with a PBM will find the assessment of the PBM industry
      timely and informative.

PMID- 12199496
TI  - Recruiting physicians and long-term viability: perspectives of physicians and
      practice managers.
AB  - As outcome measures become more informative, staffing by high quality physicians
      becomes more important to the competitive position of care providers. Success in
      physician recruiting is, therefore, a key to the long-term success and viability
      of care providers. Perceived problems in recruiting physicians led the Cincinnati
      Academy of Medicine to sponsor a study in the agreement between physician
      recruiters and physicians on the relative priority of factors affecting
      physicians' choices of practice location. The study found general agreementon
      mostof the 15 factors considered. Disagreementexisted, however, on the importance
      of salary and benefits and the importance of physicians' ability to make
      management decisions.

PMID- 12199497
TI  - Constraints on effectiveness of cyanogenic glycosides in herbivore defense.
AB  - Cyanogenesis is the process by which hydrogen cyanide is released from endogenous
      cyanide containing compounds. Many cyanogenic plants release HCN in sufficient
      quantities to be toxic and, as a result, tend to be avoided by herbivores.
      However, there are many exceptions with some herbivores either immune to the
      cyanogenic status of the plant, or in some cases attracted to cyanogenic plants.
      This has led to a certain degree of scepticism regarding the role of cyanogenic
      glycosides as defense compounds. In this review, we examine evidence showing that
      differences in the effectiveness of cyanogenic glycosides in deterring herbivory
      can usually be reconciled when the morphology, physiology, and behavior of the
      animals, together with the concentration of cyanogenic glycosides in the host
      plant, are taken into account. Cyanogenic glycosides are not effective against
      all herbivores, and not all cyanogenic plants release enough cyanide to be
      considered toxic. Nevertheless, they do form part of the broad spectrum of toxic
      and distasteful compounds that herbivores must accommodate if they are to feed on
      cyanogenic plants.

PMID- 12199498
TI  - (R)-(+)-palasonin, a cantharidin-related plant toxin, also occurs in insect
      hemolymph and tissues.
AB  - Gas chromatographic and mass spectroscopic analyses of extracts of cantharidin
      containing meloid, clerid, and staphylinid beetles revealed the presence of minor
      to significant amounts of palasonin, previously only known from seeds and fruits
      of the Indian shrub Buteafrondosa (Leguminaceae). Unlike (S)-(-)-palasonin (> 99%
      ee) from B. frondosa, the insects produce palasonin of low ee with the (R)-(+)
      enantiomer (0-50% ee) prevailing. The ee of palasonin from individual specimens
      of predatory insects (Trichodes apiarius), which acquire their chemical
      protection from cantharidin-producing insects, may vary considerably. The
      absolute configuration of (S)-(-)-palasonin, previously deduced from indirect
      chemical and spectroscopic methods, was confirmed by X-ray crystal structure
      analysis of a cyclic imide derived from (S)-(-)-palasonin and (S)-(-)- 1 -(4
      nitrophenyl)-ethylamine.

PMID- 12199499
TI  - Gut-based antioxidant enzymes in a polyphagous and a graminivorous grasshopper.
AB  - Graminivorous species of grasshoppers develop lethal lesions in their midgut
      epithelia when they ingest tannic acid, whereas polyphagous grasshoppers are
      unaffected by ingested tannins. This study tests the hypothesis that polyphagous
      species are defended by higher activities of antioxidant enzymes (constitutive or
      inducible) in their guts than are graminivorous species. Comparisons were made
      between four antioxidant enzymes: superoxide dismutase (SOD), catalase (CAT),
      ascorbate peroxidase (APOX), and glutathione transferase peroxidase (GSTPX).
      Enzyme activities were measured in the gut lumens and midgut tissues of
      Melanoplus sanguinipes (polyphagous) and Aulocara ellioti (graminivorous). The
      results of this study do not support the hypothesis that M. sanguinipes is better
      defended by antioxidant enzymes than is A. ellioti, nor are these enzymes more
      inducible in M. sanguinipes than in A. ellioti when insects consume food
      containing 15% dry weight tannic acid. Instead, tannic acid consumption reduced
      SOD, APOX, and GSTPX activities in both species. This study reports the first
      evidence that SOD is secreted into the midgut lumen in insects, with activities
      two- to fourfold higher than those found in midgut tissues. The spatial
      distribution of GSTPX and APOX activities observed in both species suggests that
      ingested plant antioxidant enzymes may function as acquired defenses in
      grasshoppers. In addition, the results of this study permit the first comparison
      between the antioxidant enzyme defenses of Orthoptera and Lepidoptera. Most
      notably, grasshoppers have higher SOD activities than caterpillars, but
      completely lack APOX in their midgut tissues.

PMID- 12199500
TI  - Dietary and developmental influences on induced detoxification in an oligophage.
AB  - Many plant secondary compounds induce detoxification activity in herbivorous
      insects. Although inducibility may be advantageous as a means of reducing costs
      associated with maintenance of metabolism, another benefit of inducibility is
      that it may allow insects to tailor their detoxification profiles to multiple
      substrate toxins in their diets. The parsnip webworm, Depressaria pastinacella,
      must contend with many types of furanocoumarins, toxins present in abundance in
      all of its host plants. Previous studies have documented that cytochrome P-450s
      are responsible for metabolism of furanocoumarins in this species and that this
      overall activity is inducible. In this study, we examined the effects of
      ingestion of single furanocoumarins on metabolism of multiple furanocoumarins and
      the ability of webworms to adjust their metabolism profiles to match artificial
      diets with furanocoumarin content differing qualitatively and quantitatively from
      the average content found in their principal host. That detoxification rates of
      newly molted sixth instars prior to feeding did not differ from those of actively
      feeding fifth or sixth instars suggests that constitutive activities of
      furanocoumarin-metabolizing enzymes are maintained in the absence of substrates.
      All of the induction assays in this study were performed with ultimate instars.
      Each of the furanocoumarins assayed was found to induce metabolism of five
      different furanocoumarin substrates; however, the induction profile was
      independent of the inducing agent. Consistent with this finding, webworms were
      incapable of matching their detoxification profiles to diets with different
      furanocoumarin compositions. Thus, the profile of detoxification within
      individuals of this species appears to be genetically fixed, although there is
      considerable variation in profiles among individuals.

PMID- 12199501
TI  - Effects of furanocoumarins on feeding behavior of parsnip webworms Depressaria
      pastinacella.
AB  - The parsnip webworm, Depressaria pastinacella, exhibits limited physiological
      resistance to furanocoumarin toxins in its principal host, the wild parsnip,
      Pastinaca sativa. These insects are typically found attacking individual plants
      low in furanocoumarins, relative to others within populations. They also feed
      preferentially on parthenocarpic fruits, which are lower in furanocoumarin
      content than are normal fruits. However, in a previous study with artificial
      diets, they did not appear to discriminate between high and low concentrations of
      furanocoumarins. In this study, the ability of webworms to distinguish between
      diets differing in furanocoumarin content was examined with an artificial diet
      containing wild parsnip and in green parsnip fruits with and without supplemental
      furanocoumarins. Larvae showed no preference for high or low furanocoumarin diets
      containing equal amounts of freeze-dried parsnip fruit powder. When given a
      choice between otherwise similar wild parsnip fruits, webworms strongly preferred
      fruits that were not augmented with furanocoumarins in one plant but showed no
      preference or only a weak preference for nonaugmented fruits in four other
      plants. In order to identify chemical constituents other than furanocoumarins
      that might determine feeding preferences, we compared the chemical profile of
      parthenocarpic fruits (which are preferred) to that of normal fruit. Octyl
      butyrate, a known deterrent to webworms, is highly correlated with furanocoumarin
      content, occurs in all plants, and differs significantly among normal and
      parthenocarpic fruit, suggesting that webworms may be able to avoid
      furanocoumarins by virtue of their behavioral response to octyl butyrate.

PMID- 12199502
TI  - Experimental studies of the host-finding behavior of Trogus pennator, a
      parasitoid of swallowtail butterflies.
AB  - The parasitic wasp Troguspennator (Hymenoptera: Ichneumonidae) attacks larvae in
      two genera of Papilionidae, Eurytides and Papilio, on plants in a variety of
      families. The female wasps' responses to food plants, feeding damage, and frass
      were examined in a series of experiments designed to test the hypothesis that
      parasitic wasps that specialize on host taxa and seek their hosts in a variety of
      habitats exhibit fixed responses to host-derived cues and more flexible responses
      to cues associated only with the hosts' food plants. Naive T pennator females
      showed no preferences when offered either a choice between two papilionid food
      plants or a choice between a food plant and a plant not used for food by
      Papilionidae. After experience with hosts in the presence of a particular food
      plant, however, wasps preferred that plant. Naive wasps did prefer plants damaged
      by host larvae over plants damaged by nonhost (saturniid) larvae and also
      preferred methylene chloride extracts of host frass over extracts of frass from
      saturniid larvae fed on the same plant species, results indicating that the
      responses of T. pennator females to host-derived cues are innate. The chemical
      compositions of the extracts of frass from several papilionid and one saturniid
      species were also examined, and the significance of the finding that no host
      specific patterns were detected among the major components of the extracts is
      discussed.

PMID- 12199503
TI  - Seed chemistry of Sophora chrysophylla (mamane) in relation to diet of specialist
      avian seed predator Loxioides bailleui (palila) in Hawaii.
AB  - This study describes the chemical ecology of a tritrophic interaction among
      species endemic to the island of Hawaii, USA: a tree (Sophora chrysophylla:
      mamane), an endangered bird (Loxioides bailleui; palila), and moth larvae (Cydia
      spp.). Palila and Cydia both specialize on the seed embryos of mamane but avoid
      eating the seed coats. Palila actively seek out and feed mamane embryos and Cydia
      larvae to their nestlings. Because mamane embryos contain potentially toxic
      levels of alkaloids, including broadly toxic quinolizidine alkaloids, and because
      insects often sequester alkaloids from their food plants, we focus on the
      questions of why palila forage upon mamane embryos and why they supplement their
      diet with Cydia larvae. Our data show that mamane embryos contain high amounts of
      potentially toxic alkaloids, but are well balanced nutritionally and contain
      lipids, carbohydrates, proteins, amino acids, and minerals at levels that are
      likely to be sufficient for maintenance and breeding. Mamane seed coats contain
      lower levels of alkaloids and nutrients, somewhat higher levels of phenolics, and
      much higher levels of nondigestible fiber. Taken together, these results suggest
      that palila have evolved tolerance to high levels of alkaloids and that they
      forage upon embryos primarily because of their availability in the habitat and
      high nutritional reward. Our data also suggest that Cydia are used by palila
      because they are readily accessible, nontoxic, and nutritious; the larvae
      apparently do not sequester alkaloids while feeding upon mamane seeds. Our
      results are interpreted with respect to the likelihood of current and historical
      coadaptive responses in this ecologically isolated and simplified island setting.

PMID- 12199504
TI  - A lectin-like wheat gene responds systemically to attempted feeding by avirulent
      first-instar Hessian fly larvae.
AB  - Through gene-for-gene interactions, wheat plants respond to specific biotypes of
      Hessian fly upon the initiation of first-instar larval feeding. Leaves of plants
      containing the H9 resistance gene responded to avirulent biotype L. larvae with
      rapid changes in the levels of several mRNA transcripts and initiation of an
      incompatible interaction. A low-copy gene, Hfr-1 (Hessian fly-response gene 1),
      responded with increased mRNA levels for two days before returning to
      preinfestation levels by day five. Hfr-1 mRNA was constitutively expressed in
      uninfested control plants as well as in plants infested with virulent larvae. The
      cDNA sequence was similar to a maize gene encoding a beta-glucosidase aggregating
      factor (BGAF), to jacalin-like mannose-binding lectins, and to several plant
      genes that respond to microbial infections. The potential roles of Hfr-1 in
      defending wheat against Hessian fly damage are discussed.

PMID- 12199505
TI  - Polymorphism in major urinary proteins: molecular heterogeneity in a wild mouse
      population.
AB  - Major urinary proteins (MUPs) are present in high levels in the urine of mice,
      and the specific profile of MUPs varies considerably among wild-caught
      individuals. We have conducted a detailed study of the polymorphic variation
      within a geographically constrained island population, analyzing the MUP
      heterogeneity by isoelectric focusing and analytical ion exchange chromatography.
      Several MUPs were purified in sufficient quantities for analysis by electrospray
      ionization mass spectrometry and MALDI-TOF mass spectrometry of endopeptidase Lys
      C peptide maps. The results of such analyses permitted the identification of
      three new MUP allelic variants. In each of these proteins, the sites of variation
      were located to a restricted segment of the polypeptide chain, projecting to a
      patch on the surface of the protein, and connected to the central lipocalin calyx
      through the polypeptide backbone. The restriction of the polymorphic variation to
      one segment of the polypeptide may be of functional significance, either in the
      modulation of ligand release or in communication of individuality signals within
      urinary scent marks.

PMID- 12199507
TI  - Comparative studies of female sex pheromone components and male response of the
      corn stalk borer Sesamia nonagrioides in three different populations.
AB  - Studies to determine possible differences in the pheromone communication system
      of three different populations of the corn stalk borer Sesamia nonagrioides
      (Lef.) in France. Spain. and Greece were carried out. The two main pheromone
      components (Z)-11-hexadecenyl acetate (Z11-16:Ac) and (Z)-11-hexadecenol (Z11
      16:OH), were detected in all analyses with very small differences in the three
      populations. Among the minor components, analyzed by GC-MS on concentrated gland
      extracts from French and Greek origin females, (Z)-l1-hexadecenal (Z11-16:Ald)
      was detected in minor amounts. Wind-tunnel and field studies revealed similar a
      male response in the three populations to pheromone glands extracts and synthetic
      pheromone regardless of the female/male origin. The results do not support the
      assumption of the existence of different pheromone types of the corn stalk borer
      S. nonagrioides due to geographic isolation.

PMID- 12199506
TI  - Heritable variation of sex pheromone composition and the potential for evolution
      of resistance to pheromone-based control of the Indian meal moth, Plodia
      interpunctella.
AB  - The short-term evolutionary effect of pheromone-based mating disruption on the
      mating ability of the Indian meal moth, Plodia interpunctella, was investigated.
      Three independent selection lines were established, and the mating ability of
      moths in plastic tents treated with high doses of pheromone and in control tents
      was compared for two consecutive generations. In addition, the heritability of
      the sex pheromone blend, measured as the ratio of two major pheromone components
      (Z,E)-9,12-tetradecadienyl acetate and (Z,E)-9,12-tetradecadienol, was estimated.
      Based on a mother-daughter regression analysis including 21 families, the
      heritability of the pheromone blend was 0.65 +/- 0.14, indicating a potential for
      evolutionary change of the character. However, no increase in mating ability of
      females in pheromone-treated tents or alteration of the pheromone blend was
      observed in any selection line when compared with control lines, indicating no or
      weak selection on the pheromone blend as well as other traits influencing mating
      ability of this species under the created mating disruption conditions. Factors
      contributing to the lack of selection effects are discussed.

PMID- 12199508
TI  - Sex attractants for moths of Vietnam: field attraction by synthetic lures baited
      with known lepidopteran pheromones.
AB  - Screening tests of synthetic lepidopteran sex pheromones were carried out at
      orchards in the Mekong Delta over an approximately two-year period starting from
      December 1998. Monoenyl acetates with a C10-C14 chain attracted six species
      distributed mainly in Southeast Asia: Adoxophyes privatana, Archips atrolucens,
      and Meridemisfurtiva in the Tortricidae family, and Argyrogramma signata.
      Spodoptera pectinicornis, and Zonoplusia ochreata in the Noctuidae family. These
      were in addition to three other noctuid species that had been attracted during
      previous field examinations within a temperate zone. Furthermore, male moths of
      three species belonging to the Cosmopterigidae, Gelechiidae, or Batrachedridae
      family were also caught by traps baited with acetates. Trienes with a C18-C21
      chain and their monoepoxides. which are stereotypes of pheromones secreted by
      females in the Geometridae family, failed to attract any geometrid male, but
      attracted three Noctuidae species and four Arctiidae species.

PMID- 12199509
TI  - Oligosaccharide composition and pheromonal activity of male tergal gland
      secretions of the German cockroach, Blattella gennanica (L.).
AB  - In the sequential courtship behavior of the German cockroach, Blattella germanica
      (Dictyoptera: Blattellidae), females feed on the tergal gland secretions from the
      male tergites. The phagostimulative components in the male secretions were
      composed of a complex mixture of oligosaccharides and phospholipids. Besides
      seven oligosaccharides previously identified, two new trisaccharides, O-alpha-D
      glucopyranosyl-(1 --> 6)-alpha-D-glucopyranosyl alpha-D-glucopyranoside and O
      alpha-glucopyranosyl-(1 --> 4)-O-alpha-glucopyranosyl-(1 --> 1)-myo-inositol,
      were characterized as the sugar components of the secretions. The activity of the
      sugar components was compared in combination with the lipid fraction. Individual
      oligosaccharides exhibited the activity either alone or synergistically with the
      phospholipids. A complex mixture of these primary substances in the tergal gland
      secretions, thus, serves as a pheromonal phagostimulant in the precopulatory
      behavior, strongly eliciting feeding response in the female cockroach.

PMID- 12199510
TI  - Attention versus competition.

PMID- 12199511
TI  - Distinguishing healthy from otosclerotic ears: effect of probe-tone frequency on
      static immittance.
AB  - The diagnostic utility of static immittance (SI) with respect to distinguishing
      healthy from otosclerotic ears was investigated at different probe-tone
      frequencies in 68 healthy ears and 36 ears with surgically confirmed
      otosclerosis. Because one effect of otosclerosis is to shift the resonant
      frequency of the middle ear to higher values as a result of increased stiffness
      of the middle ear system, it was hypothesized that SI measured at higher probe
      tone frequencies may provide a better distinction between healthy and
      otosclerotic ears. As expected, the results of this study indicate that SI
      measured at higher probe-tone frequencies is superior to a standard low probe
      tone in the detection of otosclerotic ears. Through systematic and objective
      comparisons of relevant probetone frequencies using both group statistics and
      test performance analysis, the present study suggests 630 Hz as an optimum probe
      tone frequency for measuring SI with respect to distinguishing healthy ears from
      otosclerotic ears.

PMID- 12199512
TI  - Performance of custom-fit versus fixed-format hearing aids for precipitously
      sloping high-frequency hearing loss.
AB  - This study compared the real-ear response provided by custom-fit hearing aids to
      the closest matching fixed-format disposable hearing aids in patients with
      precipitous high-frequency hearing loss. Laboratory and field measures of aided
      performance were obtained to compare patient performance with the custom-fit and
      fixed-format hearing aids. In addition, coupler versus real-ear response
      differences were compared for the two hearing aid types. The results revealed
      that relatively close approximations to the real-ear aided responses of the
      custom-fit instruments were possible for most participants using seven fixed
      acoustic formats. No significant differences in mean performance between the two
      instrument types were observed for aided speech recognition or field ratings of
      aided performance, although mean patient satisfaction was lower for the
      disposable hearing aids. The real-ear to coupler difference was greater for the
      disposable hearing aid than for the custom-fit instruments, presumably owing to
      its deeper insertion into the ear canal.

PMID- 12199513
TI  - Auditory brainstem response, middle latency response, and late cortical evoked
      potentials in children with learning disabilities.
AB  - Auditory evoked potentials (AEPs) and behavioral tests were used to evaluate
      auditory processing in 10 children aged 7 to 11 years who were diagnosed as
      learning disabled (LD). AEPs included auditory brainstem responses (ABRs), middle
      latency responses (MLRs), and late cortical responses (P1, N1, P2, P3). Late
      cortical responses were recorded using an active listening oddball procedure.
      Auditory processing disorders were suspected in the LD children after a
      psychologist found phonologic processing and auditory memory problems. A control
      group of 10 age- and gender-matched children with no hearing or reported learning
      difficulties was also tested. Teacher ratings of classroom listening and SCAN
      Competing Words and Staggered Spondaic Word scores were poorer in the LD
      children. There were minor ABR latency differences between the two groups. Wave
      Na of the MLR was later and Nb was smaller in the LD group. The main differences
      in cortical responses were that P1 was earlier and P3 was later and smaller in
      the LD group.

PMID- 12199514
TI  - Electrophysiologic correlates of attention versus distraction in young and
      elderly listeners.
AB  - This study examined the effects of selective attention versus stimulus
      competition on the late auditory evoked potential (LAEP) in 20 young and 20
      elderly listeners. In a series of test runs, different oddball tonal sequences
      were presented to one or both ears, and listeners were instructed to attend to
      tones at a specific target ear. Peak amplitudes were recorded for the N1, P2, and
      the early and late N2 components of the LAEP. Significant attention effects were
      found for all four components. N1 amplitudes increased significantly when
      participants attended to the target stimuli, whereas the amplitudes of P2, N2e,
      and N21 decreased. For all LAEP components except N21, the attention effect did
      not differ between young and elderly listeners. Significant competition effects
      also were found for all four components. Amplitudes were significantly larger in
      monaural than binaural conditions for all components except N21. The magnitude of
      this competition effect also was significantly larger for the young listeners
      than the elderly for all components except N1. These results suggest that the
      ability to attend selectively to sounds may be more resistant to normal aging
      than are effects related to stimulus competition.

PMID- 12199515
TI  - Seasonal effects on transient evoked otoacoustic emission screening outcomes in
      infants versus 6-year-old children.
AB  - The purpose of this study was to compare transient evoked otoacoustic emission
      (TEOAE) screening outcomes (pass/fail) across the seasons (spring, autumn, and
      winter) between infants and schoolchildren. A total of 526 infants (275 boys, 251
      girls) with a mean age of 2.0 months (SD = 0.38 months) and 975 schoolchildren
      (513 boys, 462 girls) with a mean age of 6.2 years (SD = 0.36 years) were
      screened using the ILO Otodynamics Quickscreen program. The same TEOAE pass/fail
      criterion was applied to the two groups. The results indicated a significant
      difference in pass rates between infants (91.2% of 1052 ears) and schoolchildren
      (86.0% of 1950 ears). A seasonal effect was found only for schoolchildren, with a
      significantly lower pass rate in winter than in spring or autumn. There was no
      difference in pass rates between spring and autumn. Implications for the seasonal
      effect on TEOAE screening outcomes for infants and schoolchildren are discussed.

PMID- 12199516
TI  - Involvement of homeobox genes in early body plan of monocot.
AB  - Homeobox genes are known as transcriptional regulators that are involved in
      various aspects of developmental processes in many organisms. In plants, many
      types of homeobox genes have been identified, and mutational or expression
      pattern analyses of these genes have indicated the involvement of several classes
      of homeobox genes in developmental processes. The fundamental body plan of plants
      is established during embryogenesis, whereas morphogenetic events in the shoot
      apical meristem (SAM) continue after embryogenesis. Knotted1-like homeobox genes
      (knox genes) are preferentially expressed in both the SAM and the immature
      embryo. Therefore, these genes are considered to be key regulators of plant
      morphogenesis. In this review, we discuss the regulatory role of knox genes and
      other types of homeobox genes in SAM establishment during embryogenesis and SAM
      maintenance after embryogenesis, mainly in rice.

PMID- 12199517
TI  - Non-coding ribonucleic acids--a class of their own?
AB  - Non-coding ribonucleic acids (RNAs) do not contain a peptide-encoding open
      reading frame and are therefore not translated into proteins. They are expressed
      in all phyla, and in eukaryotic cells they are found in the nucleus, cytoplasm,
      and mitochondria. Non-coding RNAs either can exert structural functions, as do
      transfer and ribosomal RNAs, or they can regulate gene expression. Non-coding
      RNAs with regulatory functions differ in size ranging from a few nucleotides to
      over 100 kb and have diverse cell- or development-specific functions. Some of the
      non-coding RNAs associate with human diseases. This chapter summarizes the
      current knowledge about regulatory non-coding RNAs.

PMID- 12199518
TI  - Three-dimensional progression of programmed death in the rice coleoptile.
AB  - Plant death during development is a highly orchestrated process at the cellular,
      tissue, organ, and whole-plant levels. The process toward death is endogenously
      programmed in plants. With our original approach called "three-dimensional
      analysis" using the rice coleoptile, we revealed detailed morphological
      alterations in the progression of senescence and programmed cell death involved
      in the air space (aerenchyma) formation at both tissue and cellular levels.
      Although these two types of cell death exhibited a distinct pattern of
      progression at the tissue level, the set of intracellular events was highly
      conserved. From those comprehensive investigations, we hypothesized that the
      identical program of death functions in each process of cell death, and that the
      initiation and progression of cell death is highly regulated by the environmental
      input.

PMID- 12199519
TI  - Telomeres in mammalian male germline cells.
AB  - Telomeres are terminal chromosomal domains that protect chromosome ends from
      degradation and fusion and promote complete replication of DNA. Telomeres are
      involved in the regulation of cellular replicative lifespan and tumorigenesis.
      These important functions of the telomeres have evoked high interest: numerous
      studies have resulted in a detailed description of telomere composition and
      structure in somatic cells. Much less is known about telomeres in germline cells.
      Emerging novel features and unique behavior of telomeres in the process of gamete
      differentiation suggest that they may have additional germline-specific
      function(s). This review describes recent studies revealing changes in the
      telomere organization in the course of differentiation from the germline stem
      cells to mature sperm in mammals. Similarities and differences between somatic
      and spermatogenic cells in telomere nuclear localization, protein composition,
      DNA length, telomerase activity, and chromatin structure are discussed. The
      exceptional features of the germline telomeres may be important for regulation of
      telomerase activity during spermatogenesis, homologous chromosome pairing during
      recombination, as well as for male pronucleus development and ordered chromosome
      withdrawal post-fertilization.

PMID- 12199520
TI  - Evolutionary aspects of cellular communication in the vertebrate hypothalamo
      hypophysio-gonadal axis.
AB  - This review emphasizes the comparative approach for developing insight into
      knowledge related to cellular communications occurring in the hypothalamus
      pituitary-gonadal axis. Indeed, research on adaptive phenomena leads to
      evolutionary tracks. Thus, going through recent results, we suggest that
      pheromonal communication precedes local communication which, in turn, precedes
      communication via the blood stream. Furthermore, the use of different routes of
      communication by a certain mediator leads to a conceptual change related to what
      hormones are. Nevertheless, endocrine communication should leave out of
      consideration the source (glandular or not) of mediator. Finally, we point out
      that the use of lower vertebrate animal models is fundamental to understanding
      general physiological mechanisms. In fact, different anatomical organization
      permits access to tissues not readily approachable in mammals.

PMID- 12199521
TI  - Improvements in the measurement of stool decay-accelerating factor in the
      detection of colorectal cancer.
AB  - We have previously developed an enzyme-linked immunosorbent assay (ELISA) to
      measure stool decay-accelerating factor (DAF) and found that stool DAF
      concentrations were significantly elevated in patients with colorectal cancer,
      suggesting that the measurement of stool DAF may be valuable for the detection of
      colorectal cancer. In order to refine the assay for the measurement of stool DAF,
      we investigated 1) effects of centrifugation of stool samples, 2) effects of
      detergents, and 3) adequate combination of various anti-DAF monoclonal antibodies
      for the ELISA system using only monoclonal antibodies. We found that high-speed
      centrifugation could be omitted and that only the removal of large undigested
      food residues by centrifugation of short duration in a low-speed benchtop
      microcentrifuge sufficed to adequately prepare the stool samples. Addition of 2
      detergents, octyl beta-glucoside and sodium deoxycholate, known to solubilize
      glycosyl-phosphatidylinositol-anchored proteins such as DAF, did not influence
      stool DAF values. By using 2 mouse anti-DAF monoclonal antibodies (clone 4F11 and
      1C6), we were able to achieve a stable ELISA for the measurement of stool DAF
      using a uniform source of antibodies. The results should allow us to consistently
      apply the DAF assay for routine use in the detection of colorectal cancer.

PMID- 12199522
TI  - Comparative morphological differences between umbilical cords from chronic
      hypertensive and preeclamptic pregnancies.
AB  - To compare morphological changes in the umbilical cords from chronic hypertensive
      and preeclamptic patients having normal or pathological umbilical artery Doppler
      ultrasonographic results. Umbilical cords from 34 normotensive, 31 chronic
      hypertensive and 70 preeclamptic women with normal and abnormal Doppler flow
      velocity waveforms (FVW) at 35-40 gestational weeks were studied. Morphological
      changes in the umbilical cords were examined on formalin-fixed, paraffin-embedded
      sections. The total umbilical cord area, total vessel area, and wall thickness of
      umbilical vessels were measured in systematic random samples using unbiased
      stereology methods. An ANOVA test was used for statistical analysis. In the
      chronic hypertensive and preeclamptic groups with normal Doppler FVW, the
      thickness of the umbilical cord vessels remained nearly constant, whereas both
      the total area and the lumen area were reduced. These changes correlate with the
      histopathological findings, suggesting a mainly vasoconstrictive effect. By
      contrast, analysis of the preeclamptic group with pathologic Doppler FVW showed a
      comparable reduction of all parameters of the umbilical cord. Histopathological
      findings were related to smaller, contracted smooth muscle cells of the vessel
      wall, which is suggestive of a predominant hypoplastic mechanism. As a result of
      reduced uteroplacental perfusion, fetal hypoxia and intrauterine growth
      retardation become unavoidable in preeclampsia. The histopathological changes in
      the umbilical cord between the chronic hypertensive and preeclamptic patients
      depend on the Doppler results. In conclusion, the umbilical artery Doppler FVW
      indices provide good values for predicting intrauterine growth retardation in
      preeclamptic patients.

PMID- 12199523
TI  - Identification of a target antigen recognized by a mouse monoclonal antibody to
      the bile canalicular surface of rat hepatocytes with a random phage display
      library.
AB  - We developed a monoclonal antibody (MoAb) (clone 5E8) against an antigen on the
      bile canalicular membrane of rat hepatocyte. By immunoblotting, MoAb 5E8 detected
      a band of 110 kD. In this study, we used the phage display technique to identify
      the target antigen recognized by MoAb 5E8. We screened a random phage display
      library expressing 12-mer peptide sequences and identified a peptide sequence,
      FHFNPYTGHPLT, as an epitope. We compared this peptide sequence with those of
      dipeptidyl peptidase IV (DPP IV, E.C.3.4.14.5) and Cell-CAM105, which proteins
      were located by a database search based on the information of tissue localization
      and approximate molecular weight of the MoAb 5E8 antigen, and sequence similarity
      with a region in DPP IV (amino acids 225-233) but not with Cell-CAM105 was found.
      In addition, we immunohistochemically stained various tissues (liver, small
      intestine, and kidney) of Japanese Fischer 344 rats, known to be deficient for
      DPP IV, with MoAb 5E8 and showed that the expression of MoAb 5E8 antigen was
      negligible or weak. In contrast, tissues sampled from the same organs of Sprague
      Dawley rats, known to express DPP IV, were positively stained. These findings
      suggest that the antigen recognized by MoAb 5E8 is DDPIV and its major epitope is
      located in amino acids at positions 225-233.

PMID- 12199524
TI  - Mutations in the hepatitis B virus preS2 region and abrogated receptor activity
      for polymerized human albumin.
AB  - The preS2 region of the hepatitis B virus (HBV) has been reported to have human
      polymerized albumin receptor (PAR) activity, which correlates with viral
      replication. Here, we studied the genomic sequence of the preS region from rare
      patients lacking PAR activity, despite active viral replication. PAR and DNA
      polymerase activity was identified in 178 HBe antigen-positive HBV carriers, and
      a significant correlation between 2 markers was shown, except in 2 hepatitis
      patients lacking PAR activity. Nucleotide sequences of the preS region of HBV
      from both patients were examined by direct sequencing of PCR products. In one
      patient, a 45-base deletion was found to overlap half of the putative polymerized
      human albumin binding site in the preS2 region. In the other patient, a point
      mutation at the first nucleotide of the start codon of the preS2 region of HBV
      was found. There was no such genomic change in the 3 control HBV sequences. These
      results indicate that the preS2 region is necessary for binding of polymerized
      human albumin, and this is the first report of naturally existing mutant virus
      with no or low PAR activity.

PMID- 12199525
TI  - Effects of phlebotomy on the growth of ferric nitrilotriacetate-induced renal
      cell carcinoma.
AB  - The ferric nitrilotriacetate-induced carcinogenesis model is unique in that
      reactive oxygen species-free radicals are involved in the carcinogenic process.
      But the effects of iron-withdrawal in the progression of renal cell carcinoma are
      not well understood. We performed repeated phlebotomies on animals that had been
      administered ferric nitrilotriacetate in the initiation stage of renal cell
      carcinoma (phlebotomy group), and compared the development of renal tumors with
      those not receiving repeated phlebotomies (non-phlebotomy group). Ferric
      nitrilotriacetate-treated male Wistar rats were randomly divided into 2 groups: a
      phlebotomy group (21 rats) and a non-phlebotomy group (17 rats). Ten age-adjusted
      normal rats were also observed as a normal group. Hematocrit was maintained under
      25% in the phlebotomy group. Hematocrit levels in the normal group and in the non
      phlebotomy group were not significantly different. As a result, the incidence of
      renal cell carcinoma was not significantly different between phlebotomy and non
      phlebotomy animals. However, the total weight of the renal cell carcinoma was
      significantly heavier in the animals from non-phlebotomy group than in those from
      the phlebotomy group (23.64 g +/- 18.54 vs. 54.40 g +/- 42.40, P < 0.05). The
      present study demonstrated that phlebotomy after the administration of ferric
      nitrilotriacetate did not reduce the incidence of renal cell carcinoma. In
      addition, we showed that iron withdrawal at the promotion stage of carcinogenesis
      will retard tumor growth.

PMID- 12199526
TI  - Localization of dynamin 2 in rat seminiferous tubules during the spermatogenic
      cycle.
AB  - Dynamin is a protein essential to endocytosis. Dynamin 2, a dynamin isoform, is
      expressed most intensely in testicular tissue; however, precise localization has
      never been studied. Therefore, we investigated the expression of dynamin 2 in rat
      testicular tissue using immunohistochemical methods, and discuss here the
      physiological function of this protein. Testicular tissues were obtained from
      Wistar rats at 10, 21 and 63 days of age. Immunohistochemistrical examination and
      Western blot analysis were conducted using dynamin 2 specific antibody. Western
      blot analysis showed that expression in 21- and 63-day-old rats was more intense
      than that in 10-day-old rats. Dynamin 2 expression was observed using
      immunohistochemical method in the seminiferous tubules of all rats. In the 63-day
      old rats, the expression was intense, especially in spermatids in the earlier
      maturation stages and in spermatocytes, and was observed in Sertoli cells.
      However, in spermatids, the expression gradually declined as spermatids matured
      to spermatozoa. In the 21-day-old rats, the expression was evident in
      spermatocytes and Sertoli cells, but that in the 10-day-old rats was weak.
      Intense expression of dynamin 2 during spermatogenesis suggests that this protein
      plays an important role in this process.

PMID- 12199527
TI  - Establishment of a novel collagenase perfusion method to isolate rat pancreatic
      stellate cells and investigation of their gene expression of TGF-beta1, type I
      collagen, and CTGF in primary culture or freshly isolated cells.
AB  - In studies of the pathogenesis of pancreatic fibrosis, pancreatic stellate cells
      (PSCs) have recently gained attention. In the present study, we established a new
      collagenase perfusion method through thoracic aorta cannulation to isolate PSCs,
      and we studied gene expression of TGF-beta1, type I collagen, and connective
      tissue growth factor using primary cultured PSCs. Our method facilitated PSC
      isolation, and by our new method, 4.3 +/- 1.2 x 10(6) PSCs were obtained from a
      rat. In comparing the expression of these genes with that of hepatic stellate
      cells (HSCs), we observed a similar pattern, although PSCs expressed type I
      collagen gene earlier than did HSCs. These results suggest that PSCs may play an
      important role in fibrosis of the pancreas, as HSCs do in liver fibrosis; in
      addition, PSCs may exist in a preactivated state or may be more easily activated
      than are HSCs. We also isolated the PSCs from a WBN/Kob rat, the spontaneous
      pancreatitis rat, and compared the gene expression with that from a normal rat.

PMID- 12199528
TI  - Gastric motility in patients with recurrent gastric ulcers.
AB  - The existence of abnormal gastric motility in gastric ulcer disease remains
      controversial. The aim of this study was to characterize gastric motility in
      patients with recurrent gastric ulcers. Studies were performed in 10 control
      subjects and in 24 patients with recurrent active gastric ulcer disease as
      diagnosed by gastrointestinal endoscopy. Gastric motility was evaluated by
      cutaneous electrogastrography (EGG) and by gastric semi-liquid meal emptying. The
      EGG was recorded before and after ingestion of a test meal containing 20 mg/kg of
      acetaminophen. Patients with a dominant EGG frequency of greater than 0.06 Hz
      were defined as tachygastria, while those with a frequency of less than 0.04 Hz
      were defined as bradygastria. A transient frequency decrease, called postprandial
      dip (PD), was identified visually. The degree of gastric emptying was determined
      from the serum acetaminophen concentration 45 minutes after the meal. Control
      subjects showed no irregularity in their dominant EGG frequency in tither fasting
      or postprandial states. PD was observed in 8 control subjects. In patients
      presenting with active gastric ulcers, abnormal patterns in the dominant EGG
      frequency (either as tachygastria or bradygastria) were observed in 14 of the 24
      patients when fasting and in 15 of them in the postprandial state. After
      successful treatment, the number of patients with abnormal patterns in their
      dominant EGG frequency remained unchanged, while PD was observed in 11 patients.
      No significant difference was observed in the EGG power ratio as a result of
      successful treatment. Gastric emptying was significantly delayed compared with
      controls in both the active and healed stages. These findings suggest that
      abnormal gastric motility, including gastric electrical abnormalities and delayed
      gastric emptying, plays an important role in the pathophysiology of recurrent
      gastric ulcers.

PMID- 12199529
TI  - Unaltered caffeine-induced relaxation in the aorta of stroke-prone spontaneously
      hypertensive rats (SHRSP).
AB  - Caffeine-induced relaxation was studied in aortic segments from Wistar Kyoto rats
      (WKY) and stroke-prone spontaneously hypertensive rats (SHRSP). Although
      acetylcholine-induced endothelium-dependent relaxation was impaired in
      preparations from SHRSP, the relaxation induced by caffeine was identical in both
      groups. In addition, caffeine-induced relaxation was not affected by removal of
      the endothelium in either group. The relaxation induced by N6,2'-O
      dibutyryladenosine 3':5'-cyclic monophosphate (db-cAMP), a membrane-permeable
      analog of adenosine 3':5'-cyclic monophosphate (cAMP), was identical in both
      groups. No significant difference was observed in the increase in cAMP content
      induced by caffeine in the aortic smooth muscle between the groups, although the
      basal content was significantly higher in preparations from SHRSP. These results
      suggest that the relaxation induced by caffeine in these preparations is brought
      about by its direct effect on smooth muscle and that the response of the smooth
      muscle to caffeine, including cAMP production, is not altered in preparations
      from SHRSP compared with those from WKY.

PMID- 12199530
TI  - Dual effects of cyclopiazonic acid on excitation of circular smooth muscle
      isolated from the guinea-pig gastric antrum.
AB  - The effects of cyclopiazonic acid (CPA), a known Ca2+-pump inhibitor at internal
      stores, were investigated on electrical responses of the membrane of smooth
      muscle cells in small segments (0.3-0.5 mm long) of circular smooth muscle
      isolated from the guinea-pig gastric antrum. In most preparations, the membrane
      was spontaneously active with the generation of unitary potentials and
      regenerative slow potentials. Low concentrations (< 1 microM) of CPA did not
      alter either the membrane potential or the amplitude and frequency of slow
      potentials. CPA at a concentration of 1 microM initially increased the frequency
      of slow potentials, but this was followed by a decrease in the frequency as a
      result of sustained exposure to CPA, with no alteration of either the membrane
      potential or the amplitude of slow potentials. Higher concentrations of CPA (2-5
      microM) depolarized the membrane and decreased the amplitude and frequency of
      slow potentials. CPA at higher than 10 microM abolished slow potentials with
      depolarization of the membrane. Intracellular electrical responses recorded
      simultaneously from paired cells were synchronized, indicating electrical
      coupling of the cells. Depolarization of the membrane with current stimuli
      through one electrode evoked regenerative slow potentials superimposed on the
      electrotonic potentials. The evoked slow potential had a refractory period of
      about 7 s. CPA (up to 10 microM) did not prevent the synchronization of paired
      cells. The refractory period for slow potentials was reduced by low
      concentrations of CPA (< 1 microM) and increased by higher concentrations of CPA
      (2-10 microM). These results suggest that lower concentrations of CPA produce
      excitatory actions on gastric smooth muscles due to a secondary effect of
      increased intracellular [Ca2+], while higher concentrations of CPA produce
      inhibitory actions as a result of reduced release of Ca2+ from depleted internal
      stores.

PMID- 12199531
TI  - Effects of flufenamic acid on smooth muscle of the carotid artery isolated from
      spontaneously hypertensive rats.
AB  - Endothelium-removed carotid artery strips from stroke-prone spontaneously
      hypertensive rats spontaneously developed a tonic myogenic contraction.
      Flufenamic acid reduced the resting tone observed during superfusion with
      Tyrode's solution, in a concentration-dependent manner. Flufenamic acid also
      inhibited contractions produced by high-K solutions in a concentration-dependent
      manner. The resting membrane potential of smooth muscle cells in the artery was
      around -32 mV, with occasional oscillatory potentials. Flufenamic acid
      hyperpolarized the membrane in a concentration-dependent manner. The voltage
      dependent outward currents recorded in isolated cells with micropipettes filled
      with high-K+ solution (holding potential, -60 mV) were enhanced by flufenamic
      acid and inhibited by tetraethylammonium. When the recording micropipette was
      filled with high Cs to inhibit the K+-current, depolarizing step pulses evoked
      nifedipine-sensitive inward currents. Flufenamic acid inhibited the inward
      currents. These results indicate that flufenamic acid inhibits the spontaneous
      active tone of the carotid artery by inhibiting L-type Ca2+-channels and possibly
      by membrane hyperpolarization through activation of the voltage-dependent K+
      channels.

PMID- 12199532
TI  - Positional relationships between the masticatory muscles and their innervating
      nerves with special reference to the masseter and zygomaticomandibularis in
      Suncus murinus.
AB  - In the present study, we investigated the structure and nerve innervation of the
      masseter, temporalis and zygomaticomandibularis of Suncus murinus which has no
      zygomatic arch. Detailed dissection of eight head halves of four S. murinus was
      performed. In S. murinus, small muscle bundle was observed to be adjoined with
      the lateral surface of the temporalis. This muscle bundle was completely
      separated from the masseter. Based on the positional relationships between the
      muscle bundle and supplying nerves, we conducted that the bundle corresponded to
      the zygomaticomandibularis of human described in our previous study (Shimokawa et
      al., 1999). In addition, some differences in the nerve distribution to the
      masticatory muscles were observed in S. murinus as compared with humans with
      respect to the following points: 1) The additional supplying branch to the
      masseter originated from the auriculo-temporal nerve: 2) The common trunk of the
      masseteric nerve and the nerve to the posterior part of the temporalis penetrated
      the superior head of the lateral pterygoid. A possible model to account for these
      differences based on the positional relationships among the muscles and supplying
      nerves is presented.

PMID- 12199533
TI  - Morphometric nerve fiber analysis of the human inferior alveolar nerve: lateral
      asymmetry.
AB  - We studied morphometric nerve fiber analysis and the lateral asymmetry of the
      inferior alveolar nerve (IAN). Human IANs were resected at the mandibular
      foramen. The preparation of sections involved fixation, washing, dehydration,
      embedding, sectioning and staining as described in our previous reports. We
      estimated the average total number of myelinated axons in the right IAN to be
      22,808, with an average transverse area of 37.6 microm2, an average perimeter of
      23.0 microm, and average circularity ratio of 0.85, with the same measurements in
      the left IAN being 24,289, 33.9 microm2, 21.6 microm, and 0.86, respectively.
      Morphological differences between the right and left side were analyzed by
      applying parametric tests (unpaired t-test) to all measured items. According to
      these results, the IAN did not demonstrate notable lateral asymmetry in any
      measured item. We considered that these results were caused by using subjects
      with the same dentulous condition in both sides.

PMID- 12199534
TI  - Vesicles in the subacrosomal space and partial diaphragms in the subacrosomal
      nuclear envelope of round spermatids of a rat injected intravenously with gold
      labeled-testosterone-bovine serum albumin conjugate: vesicular trafficking from
      acrosome to nucleus.
AB  - Colloidal gold labeled-testosterone-bovine serum albumin conjugate (testosterone
      BSA-gold) injected into the vascular system of rats is taken up by endocytosis
      into round spermatids. Based on observation of silver deposits indicating
      testosterone-BSA-gold with silver enhancement, we have suggested that
      testosterone-BSA-gold enters the nuclei through not only the postacrosomal
      nuclear envelope but also the subacrosomal nuclear envelope (SNE) via the
      acrosome (Nishimura and Nakano, 1997). However, it was unclear how testosterone
      BSA-gold in the acrosome entered the nucleoplasm. Spermatids showing silver
      deposits on the subacrosomal space were observed under electron microscope
      without silver enhancement, to clarify the courses of translocation. In the
      spermatids, vesicles with the gold particles were seen in the subacrosomal space.
      Some of the vesicles were in contact with the SNE. A part of the outer nuclear
      membrane projected into the space. Furthermore, local single-bilayer nuclear
      membranes, which seemed to partially lack nuclear lamina, were present in the
      SNE. These results indicate the possibility that the vesicles mediate the
      transport of testosterone-BSA-gold from acrosome to nucleus, and that the vesicle
      membrane fuses with not only the outer nuclear membrane but also a shared bilayer
      in the SNE.

PMID- 12199535
TI  - The effect of melatonin on morphological changes in liver induced by magnetic
      field exposure in rats.
AB  - In this study, we aimed to investigate the possible effect of melatonin on
      morphological changes in liver induced by magnetic fields exposure. Thirty albino
      young male Wistar Albino rats were used in the study. They were divided into 3
      groups. Control group (C) (n: 10) received daily intraperitoneal injections of
      saline (0.1 ml/100 g) containing 5% ethanol for two weeks. Only magnetic field
      exposed (MF) group (n: 10); only magnetic field exposed had daily intraperitoneal
      injections of physiologic saline (0.1 ml/100 g) containing 5% ethanol for two
      weeks. Magnetic field exposed and melatonin treated (MF+m) group (n: 10);
      melatonin was dissolved in ethanol with further dilution in physiological saline.
      The animals in this group were exposed magnetic fields for two weeks. The
      magnetic fields exposed animals had intraperitoneal single dose of 4 mg/kg
      melatonin (0.1 ml/100 g) at 10:00 o'clock daily for two weeks following magnetic
      fields exposure. We used commercial CB handheld portable transceiver, Midland
      (USA) labelled, of 4 Watts, 40 channel. This channel frequency has been measured
      27.17 MHz with frequency counter. According to the IRPA exposure standards; for
      27 MHz, for 6 min, exposure limit is 0.2 mW/cm2. This value is for General
      Public. For occupational exposure limit is 1 mW/cm2. We have to consider General
      Public exposure limit. Therefore our limit is 0.2 mW/cm2. In other words; in this
      study; our exposure is always over the recommended limit. All the animals were
      decapitated. Liver samples were fixed in buffered neutral formalin. Paraffin
      sections were dyed with hematoxylen-eosin. Sections were examined under light
      microscopy. In MF group; sinusoidal dilatations, mixed cell infiltrations noticed
      in the periportal area, necrosis and vacuoler degeneration were determined in
      liver samples. However, parenchymal and stromal structures were observed to be
      prevented partially from effects of magnetic fields in melatonin treated group.
      In conclusion, it is suggested that melatonin has a mild preventive effect on
      magnetic field exposed changes in liver tissue in the rats.

PMID- 12199536
TI  - Histoenzymology and morphometry of the masticatory muscles of tufted capuchin
      monkey (Cebus apella Linnaeus, 1758).
AB  - Samples of the anterior and posterior regions of the masseter and temporal
      muscles and of the anterior belly of the digastric muscle of 4 adult male tufted
      capuchin monkeys (Cebus apella) were removed and stained with HE and submitted to
      the m-ATPase reaction (with alkaline and acid preincubation) and to the NADH-TR
      and SDH reactions. The results of the histoenzymologic reactions were similar,
      except for acid reversal which did not occur in fibers of the fast glycolytic
      (FG) type in the mandibular locomotor muscles. FG fibers had a larger area and
      were more frequent in all regions studied. No significant differences in
      frequency or area of each fiber type were detected, considering the anterior and
      posterior regions of the masseter and temporal muscles. The frequency of fibers
      of the fast oxidative glycolytic (FOG) and slow oxidative (SO) types and of FOG
      area differed significantly between the anterior belly of the digastric muscle
      and the mandibular locomotor muscle. The predominance of fast twitch (FG and FOG)
      fibers and the multipenniform and bipenniform internal architecture of the
      masseter and temporal muscles, respectively, are characteristics that permit the
      powerful bite typical of tufted capuchin monkeys.

PMID- 12199537
TI  - Morphometrical study of the joint surface and capsule of the lumbar zygapophysial
      joint with special reference to their laterality.
AB  - Using 26 osteoligamentous lumbar vertebral columns (260 facets), we
      morphometrically investigated the cartilagenous joint surface, inner capsular
      surface and capsular thickness. We also examined whether the subcapsular pocket
      was present and, if present, how far it extended along the joint margin. The
      proportion of the inner capsular area in the total joint surface area in a facet
      (the capsular-joint surface ratio) was hypothesized to correspond to the
      potential looseness (or tightness) of the facet. The absolute data themselves
      seemed to be useful for better understanding of the joint morphology. However,
      further evaluations of the differences between segments, left/right differences,
      individual segmental fluctuation patterns and correlations between parameters
      provided a novel classification of specimens according to the hypothetical
      progress of joint degeneration. Criteria for the classification existed in 1) the
      laterality in parameters defined as more than 100% larger or smaller than the
      contralateral facet and 2) the drastic segmental difference in parameters over
      50% larger or smaller than the adjacent segment. Consequently, three types were
      identified: 1) outside of the criteria in both area and thickness (-/- type, 9 of
      26); 2) the criteria did not fit the area parameters but did fit the thickness
      parameters (-/+ type, 8); the criteria were filled in both categories of
      parameters (+/+ type, 9). Notably, in the +/+ types, the capsular thickness and
      capsular-joint surface ratio correlated significantly (p < 0.01), i.e., the
      hypothetical loose joint had a thick capsule. We speculated that early joint
      degeneration starts from the -/- type and advances via the -/+ type to the +/+
      type. Considerating these results, we recommended using MR imaging for detailed
      identification of laterality in the capsular thickness for low-back pain patients
      to discriminate candidates for future severe degenerative changes of the
      articular cartilage in the lumbar spine.

PMID- 12199538
TI  - Glaucoma: optometry helps relieve the pressure.

PMID- 12199539
TI  - An uncommon presentation of Bartonella-associated neuroretinitis.
AB  - BACKGROUND: This article documents a case of neuroretinitis initially presenting
      with ocular pain, 20/20 visual acuities, optic disc edema, and macular serous
      detachment without macular star formation in the absence of a history of exposure
      to pets or cats or symptoms suggestive of Bartonella infection. This initial
      clinical presentation appeared unilateral, but later became bilateral. CASE
      REPORT: Physical and neuroophthalmologic consultation, neuroimaging studies,
      blood chemistry, and serologic analysis were requested. Positive serologic (IGG)
      titers to Bartonella henselae and Bartonella quintana were detected. Treatment
      was instituted initially with oral tetracycline (250 mg) qid and subsequently
      with doxycycline (100 mg) bid and prednisone (20 mg) qd. CONCLUSION: Bartonella
      infection may cause optic disc edema and serous detachment without macular star
      formation. This presentation may occur without the generally characteristic signs
      and symptoms of Bartonella-associated neuroretinitis. A bilateral involvement may
      follow an initial unilateral presentation during the affliction period of this
      disorder.

PMID- 12199540
TI  - Glaucoma medical treatment--2002: does yearly cost now equal the year?
AB  - BACKGROUND: To review costs of the wide array of glaucoma medications available
      today as well as patient-assistance programs. METHODS: Potential yearly costs for
      current frequently used single and multiple drug therapies were determined,
      taking into account the actual (not labeled) volume of drops in the bottled
      medications. Alternative modes for obtaining medications, such as compassionate
      use programs, were also surveyed. RESULTS: "Maximum" medical therapy may cost
      over $2000 per year. Allergan, Ciba, Merck, Pharmacia-Upjohn, and Alcon offer
      patient-assistance programs of variable simplicity of use. DISCUSSION: The cost
      of maximum glaucoma medical therapy can assume a significant proportion of an
      elderly patient's yearly income.

PMID- 12199541
TI  - Visual performance and comfort with the Rose K lens for keratoconus.
AB  - PURPOSE: The "Rose K Lens for Keratoconus" is a proprietary rigid contact lens
      design that has been reported and marketed as a lens that provides better visual
      acuity and comfort than other rigid contact lens designs for keratoconus.
      METHODS: Twenty patients with keratoconus who were wearing rigid contact lenses
      were refitted into the Rose K lenses. Visual acuity measurements were taken with
      habitual lenses at the baseline visit and with the Rose K lenses at the
      completion of the study. Questionnaires were used to assess vision-specific
      quality of life, contact lens comfort, and self-reported assessment of vision.
      RESULTS: There were no statistically significant changes in high- or low-contrast
      visual acuity with the Rose K lenses. There was statistically significant
      improvement in self-reported assessment of vision and self-reported assessment of
      comfort in the eyes with more advanced keratoconus. At the conclusion of the
      study, 72% of patients preferred the Rose K lenses over their habitual lenses,
      and 87% reported that they would continue wearing the Rose K lenses. CONCLUSIONS:
      There was no difference in the visual acuity with the Rose K lenses compared with
      the patients' habitual lenses. Subjective assessment of vision and comfort
      indicate a statistical improvement for more advanced keratoconus with the Rose K
      lens. We could not rule out a placebo effect as a source of subjective
      improvement in vision and comfort. Nevertheless, the successful fit rate and
      patient preference demonstrate the usefulness of the Rose K lens in clinical
      practice.

PMID- 12199542
TI  - Assessing visual performance with progressive addition lenses.
AB  - PURPOSE: As a result of lens design limitations, progressive addition lenses
      (PAL's) present a limited field of view for tasks at intermediate distances, such
      as with computers. To assess whether this limitation results in diminished visual
      performance, PAL's were compared with single-vision lenses in four different
      types of reading tasks in a computer workplace environment. METHODS: Adult
      subjects performed four computer-based reading tasks using both single-vision
      lenses and PAL's at an intermediate distance of 64 cm. RESULTS: Single-vision
      lenses performed significantly better than PAL's in one task, with a trend for
      better performance in another task. There was no difference in performance for
      the remaining two tasks. CONCLUSIONS: Visual performance tests that involved
      stimuli subtending the widest visual angles and demanded more fixational shifts
      were more sensitive in discerning performance differences between the lens
      designs. In general, PAL's showed marginally diminished performance compared with
      single-vision lenses, presumably due to their restricted intermediate channel.

PMID- 12199543
TI  - Are high-pass resolution perimetry thresholds sampling limited or optically
      limited?
AB  - PURPOSE: It has been reported that high-pass resolution perimetry (HRP) provides
      a means of noninvasively determining retinal ganglion cell density. However,
      there is evidence to suggest that this may not be true. The purpose of the
      present study was to determine whether HRP thresholds are sampling limited, which
      is a necessary condition for being able to determine retinal ganglion cell
      density psychophysically. METHODS: This study measured resolution and detection
      performance for a range of grating-based stimuli under the testing conditions
      that HRP uses and compared these with performance of the ring stimulus. RESULTS:
      The results show that detection and resolution acuity under HRP test conditions
      were often equivalent, in accordance with previous investigations. However, the
      results also show that the thresholds underestimated the true level of resolution
      acuity in the periphery because increasing stimulus contrast increased
      performance. CONCLUSION: These findings suggest that HRP thresholds cannot be
      regarded as sampling limited, but rather they are optically limited. We therefore
      conclude that HRP thresholds cannot be regarded as a direct measure of the
      underlying ganglion cell density.

PMID- 12199544
TI  - Tilted power of thin lenses.
AB  - Tilting changes the effective power of a thin lens. Blendowske has recently
      provided an elegant matrix expression for the tilted power in the case of tilt
      about a vertical axis (faceform tilt). He makes use of what can be called a tilt
      matrix. He shows that the same expression holds in the case of tilt about a
      horizontal axis (pantoscopic tilt) if one makes use of a different tilt matrix.
      The purpose of this note is to derive a general tilt matrix that makes
      Blendowske's equation valid for tilt about any axis. The general tilt matrix
      reduces to the particular tilt matrices in the case of rotation about the
      horizontal and vertical axes. The lens may be stigmatic or astigmatic and may be
      in air or in some other medium.

PMID- 12199545
TI  - The measurement of vision disability.
AB  - The American Medical Association's (AMA) visual efficiency scale, a vision
      disability metric based on visual impairment measurements, was adopted in 1925.
      That scale was based on a 30-year history of theoretical models in vision
      economics, a misinterpretation of Snellen notation for visual acuity, and an
      erroneous application of Weber's psychophysical law. The AMA visual efficiency
      scale survived uncontested for 75 years. In 2001, the AMA adopted a new vision
      disability scale based on logarithmic transformations of visual acuity and visual
      field diameter. Like the earlier visual efficiency scale, the new scale is
      theoretical-it is not supported by any data that speak to the relationship
      between vision disability and visual impairments. Attempts to measure vision
      disability date to the early 1980s with the development of self-assessment visual
      function rating scale questionnaires. Nearly all of the questionnaires developed
      over the last 20 years use Likert scales, but use them incorrectly. The
      development of a vision disability metric based on Likert scaling parallels the
      historical development of other forms of measurement. A tutorial review of
      psychometrics-classical test theory, item response theory, and Rasch analysis
      shows how vision disability measurement scales can be estimated from Likert-type
      visual function rating scales. We conclude that preliminary data relating
      measures of vision disability to measures of visual acuity and visual fields
      support the new AMA vision disability scale.

PMID- 12199546
TI  - Exposure guidelines for low-frequency electric and magnetic fields: report from
      the Brussels workshop.
AB  - The EMF Exposure Guidelines Science Workshop was held to evaluate the information
      base for guidelines for electric and magnetic field exposures at extremely low
      frequencies, to identify research needs, and to discuss how best to apply
      scientific knowledge in developing exposure recommendations. Although the
      existing guideline values are based on electrostimulation of nerve and muscle
      tissues, guidelines must also consider controversial studies of potential health
      effects from chronic exposures at environmental levels that are far too weak to
      cause electrostimulation. The size of the safety factor applied in specifying
      exposure limits reflects a variety of factors that introduce uncertainties. These
      include confidence in existing dose-effect relationships, population diversity,
      the reliability and precision of techniques to control over-exposure, and
      completeness of the information base, particularly regarding long-term effects.
      Specific research questions that can change the level of uncertainty meaningfully
      were identified in these areas: biophysical mechanisms of electrostimulation; the
      range of thresholds throughout exposed populations; cancer causation in children
      and adults, including a possible role for contact currents; cognitive,
      behavioral, and physiological effects on the central nervous system; improved
      dosimetry; and better understanding of electromagnetic interference with
      implanted biomedical devices such as pacemakers, defibrillators, and
      physiological monitors. This report introduces ten papers from the workshop that
      address these and related topics in detail.

PMID- 12199547
TI  - Human body exposure to power lines: relation of induced quantities to external
      magnetic fields.
AB  - Induced electric field and corresponding current density values in various organs
      of the human body can be computed numerically using a heterogeneous, anatomically
      representative voxel model. Such computations are available for uniform magnetic
      fields of various directions with respect to the body. The highest exposure
      levels occur for non-uniform fields, most often in occupational settings. Various
      organ induced dosimetric measures of the induced quantities can also be computed,
      although the associated computational complexity and effort are greater than for
      uniform fields. A simplified method of estimation of the induced measures is
      described and validated. The method is based on evaluation of the external
      (exposure) magnetic flux density in locations corresponding to those occupied by
      various organs and dosimetry for the uniform fields. Computations of the external
      fields are relatively simple even for very complex geometries of current-carrying
      conductors. Computational methods are available for external fields. The external
      magnetic fields can also be measured. Detailed organ dosimetry is already
      published. In this contribution, the proposed simplified dosimetry is verified
      using accurate, numerically computed dosimetry for four non-uniform field
      exposure scenarios. For most dosimetric measures and organs, the proposed method
      gives conservative estimates. Only in rare cases when a large organ is in a weak
      exposure field compared to the whole-body average exposure, the induced
      dosimetric measures may be underestimated by up to 10%. Another exception is the
      maximum induced electric field in spatially distributed tissues such as bone
      marrow, muscle, or skin when a part of the limb is in a very strong magnetic
      field close to the conductor. However, both of these situations are easily
      recognizable from the mutual configuration of the human body and the current
      carrying conductors. Thus, additional corrections can be applied to the
      estimates.

PMID- 12199548
TI  - Neuroelectric mechanisms applied to low frequency electric and magnetic field
      exposure guidelines--part I: sinusoidal waveforms.
AB  - Electric and magnetic field exposure guidelines are developed from established
      mechanisms of bioelectric interaction. Such mechanisms involve phenomena of
      electrostimulation-the functional influence of applied electrical forces on nerve
      and muscle, and, at quasi-static frequencies, on magneto-dynamic mechanisms. The
      paper develops criteria of human reactions based on theoretical models with
      parametric values derived from experimental observations. These basic
      restrictions on electrostimulation effects are referenced to the induced in situ
      electric fields. Basic limitations are differentiated for induction in the heart,
      peripheral nerves, the extremities, and the central nervous system. The paper
      recommends maximum permissible exposure limits which account for (a) adverse
      reaction criteria, (b) statistical distribution of reaction thresholds, and (c)
      acceptability factors. From the basic limitations the paper further develops
      reference levels which apply to environmental electric or magnetic fields.

PMID- 12199549
TI  - Neuroelectric mechanisms applied to low frequency electric and magnetic field
      exposure guidelines--part II: non sinusoidal waveforms.
AB  - Standards for human exposure to electromagnetic fields typically express maximum
      permissible exposure limits as a function of frequency. Often, these limits have
      been derived from experiments or theoretical models involving sinusoidal
      waveforms. In many practical situations, however, the relevant waveforms of
      interest may not be sinusoidal, such as with waveforms having harmonic
      distortion, or with pulsed waveforms. This paper evaluates methods for applying
      sinusoidal exposure standards to non-sinusoidal waveforms in the frequency regime
      below a few MHz where electrostimulation is the dominant mechanism. Waveforms
      treated include those of a pulsed or mixed frequency variety. We evaluate
      acceptance criteria for mixed frequency exposure using summation formulae cited
      by IEEE C95.1, ICNIRP, and NRPB. This is carried out using a Fourier synthesis of
      various waveshapes. Also evaluated is an acceptance criterion based on the peak
      of the exposure waveform. Excitation thresholds are evaluated using a myelinated
      nerve model that accounts for the nonlinear electrodynamics of the neural
      membrane. It is shown that a method based on the peak and phase duration of the
      in situ field waveform provides a typically conservative test for compliance with
      non sinusoidal waveforms. An alternate method, based on amplitude summation of
      the Fourier components of the applied waveforms, can also provide a meaningful
      test, albeit a more conservative one.

PMID- 12199550
TI  - Weak electric field interactions in the central nervous system.
AB  - Exposure to extremely low frequency electric and magnetic fields will induce
      electric fields and currents within the body, but these are almost always much
      lower than those that can stimulate peripheral nerve tissue. Guidance on exposure
      to such fields has been published by NRPB and ICNIRP, which is based on the
      avoidance of acute effects in the central nervous system. Weak electric field
      effects, below action potential thresholds, have been demonstrated in vitro in
      brain slice preparations; thresholds can be estimated to be above about 1 mV mm(
      1) (around 100 mA m(-2), taking a brain tissue conductivity of around 0.1 S m(
      1)), depending on stimulus conditions. Some studies suggest possible effects at
      lower induced field strengths. The intact nervous system might be expected to be
      more sensitive to induced electric fields and currents than in vitro
      preparations, due to a higher level of spontaneous activity and a greater number
      of interacting neurons. There is good evidence that electrically excitable cells
      in the retina can be affected in vivo by induced currents as low as 10 mA m(-2).
      It has been suggested that induced current densities above 10 mA m(-2) may have
      effects on other central nervous system functions but few studies have been
      carried out. Further research in experimental animals using both in vitro and in
      vivo approaches is needed to clarify this issue.

PMID- 12199551
TI  - Health effects relevant to the setting of EMF exposure limits.
AB  - To date, electric and magnetic exposure limits for frequencies below 100 kHz have
      been based on vaguely defined neurobiological responses to electric fields
      induced in tissues in vivo by magnetic fields and on perceptual responses to
      external electric fields. Advances in tissue dosimetry, risk assessment methods,
      and biological research on stimulation thresholds and mechanisms are providing
      new bases for exposure limits. This paper reviews the historical basis for
      current electric and magnetic exposure limits in preparation for the development
      of the "next generation" of electric and magnetic occupational and public
      exposure guidelines. This is followed by an overview of reported neurobiological
      effects of electric and magnetic stimulation that should be considered in new
      exposure guidelines. For magnetic fields, there is stronger evidence for setting
      exposure limits to protect against adverse effects of nerve stimulation than for
      protecting against visual magnetophosphenes. Magnetophosphenes are not adverse,
      and the evidence that these perceptual responses of the eye are a precursor or
      surrogate for other adverse neurologic responses is weak. Rather than relying
      just on theoretical models to set exposure limits, data from human subjects
      exposed to pulsed magnetic fields should be used to estimate nerve stimulation
      thresholds. Such data can provide a solid basis for setting magnetic field
      exposure limits if uncertainties in the data and inter-individual variability are
      addressed. Research on sensory perception, spontaneous and evoked potentials, and
      epidemiologic studies of neuropsychiatric conditions in electric and magnetic
      exposed populations does not suggest a need for lower exposure limits. However, a
      report that a 60-mT magnetic field (below the threshold for peripheral nerve
      stimulation) produces prolonged alterations of brain excitability and
      "indisposure" of subjects should be investigated in future research.

PMID- 12199552
TI  - Candidate sites of action for microdosimetry associated with exposure to
      extremely-low-frequency magnetic fields, electric fields and contact currents.
AB  - Recent advances enable one to apply numerical techniques to anatomically-correct
      human models to compute current densities and electric fields in tissue due to
      exposure to electric fields, magnetic fields, or contact currents. These methods
      have proved to be informative in estimating exceedance of basic restrictions
      prescribed by exposure guideline organizations. To date, the analyses have been
      conducted with a resolution on the order of millimeters. However, these
      techniques have future roles to play at higher levels of resolution at those
      sites in target tissues suspected of transducing local electric fields into
      biological responses. Two specific cases in which high resolution
      "microdosimetry" would yield value involve (a) residential settings and childhood
      leukemia and (b) worker exposure and cardiovascular disease. Recent research
      suggests that residential contact currents on the order of microamperes can
      produce biologically significant dose (expressed as the local electric field) to
      the bone marrow of a child. Microdosimetry would focus on pluripotent progenitor
      cells resident in the marrow compartment, as well as anatomic features that
      distinguish a child's from an adult's marrow. Laboratory and epidemiologic
      research has suggested that magnetic field exposure may affect heart rate
      variability, a measure reflective of autonomic nervous system control of cardiac
      activity. Given the physical attributes of the central nervous system and the
      sites that could serve as substrates for field interactions, future
      microdosimetry addressing heart rate variability effects may be well-advised to
      focus on the electrically excitable dendritic arborizations of neurons. In both
      cases, microdosimetry will help shed light on primary interactions in tissue.

PMID- 12199553
TI  - Basic restrictions in EMF exposure guidelines.
AB  - Different bodies have set guidelines restricting exposure to electric and
      magnetic fields. The limits at power frequencies recommended by these guidelines
      and the scientific basis and rationale for setting them have been reviewed,
      starting with the WHO Environmental Health Criteria 69 on Magnetic Fields,
      published in 1987. These guidelines are all designed to limit the induced current
      density to 10 mA m(-2), sometimes reduced by an additional safety factor of five
      for the general public. While published guidelines have, to date, universally
      adopted a restriction based upon induced current density, the internal electric
      field is the more fundamental quantity in determining biological effects. It is
      recommended that consideration be given to using the internal electric field
      rather than current density in future guidelines. Those who are responsible for
      setting guidelines need good scientific information on which to be able to set
      their limits. While there is already a significant weight of scientific evidence
      upon which exposure restrictions can be based, there is a need for more research
      to reduce uncertainties and to enable greater precision in the setting of limits.
      Some suggestions for future research directions, particularly aimed at further
      understanding of the interaction of electric fields with the nervous system, are
      suggested in this paper and are developed more widely in the following papers
      covering the proceedings of the EPRI Guidelines Science Workshop held in Brussels
      in June 2000.

PMID- 12199554
TI  - Dealing with uncertainty in formulating occupational and public exposure limits.
AB  - Scientists are forced to address many sources of uncertainty in the setting of
      exposure limits. This paper discusses the rationale for some of the approaches
      that have been used for many years to address uncertainties encountered in the
      setting of occupational and public exposure limits to protect against non-cancer
      effects of chemicals. These approaches are quite different from the methodology
      that has been adopted for the setting of exposure limits to power-frequency
      electric and magnetic fields to avoid adverse effects of induced electric fields
      and currents. The limitations of the non-standard electric and magnetic fields
      guideline methodology are described. To address these limitations, a
      probabilistic approach to developing exposure limits for electric and magnetic
      fields has been proposed. As a demonstration, this approach has been applied to
      the estimation of magnetic field exposures that would not pose significant risks
      of cardiac stimulation from electric fields induced in the torso. The results of
      this probabilistic analysis demonstrate the importance of explicitly
      characterizing potential sources of uncertainty and variability. Furthermore, the
      use of fixed, single point estimates of dosimetric parameters by electric and
      magnetic fields guideline-setting organizations provides more than adequate
      protection to individuals from the risk of cardiac stimulation. The mean magnetic
      field level that would increase the risk of cardiac stimulation is shown by this
      approach to be about three times higher than is predicted by dosimetric formulas
      used by the ACGIH and ICNIRP. If input data for parameters affecting the risk of
      adverse effects with lower thresholds, i.e., nerve stimulation, are developed and
      validated, this method could be used in the setting of electric and magnetic
      fields standards based more strongly on quantitative assessments of experimental
      data.

PMID- 12199555
TI  - Assessing compliance with power-frequency magnetic-field guidelines.
AB  - Several organizations have established guidelines for occupational exposure to
      power-frequency magnetic fields. At 60 hertz, exposure limits are 1.0 millitesla
      (mT) for the American Conference of Governmental Industrial Hygienists, 0.42 mT
      for the International Committee on Non-ionizing Radiation Protection, and 1.6 mT
      for the National Radiation Protection Board guidelines. Adoption of the current
      guidelines as mandatory standards could dramatically affect electric-utility work
      practices. Two large personal-exposure monitoring projects have characterized
      exposures of overhead lineworkers and cable splicers while they perform various
      tasks near energized conductors. Personal exposure measurements indicate that
      these two groups are very likely the most highly exposed among utility workers
      and often experience fields above guideline levels. In addition, survey
      measurements in utility environments have identified locations where other
      workers may experience exposures at guideline levels. The nature of high-field
      exposure scenarios in the utility industry suggests a simple practical method for
      determining compliance with basic restrictions on internal induced current
      density [< 10 milliamperes per square meter (mA m(-2))] in the presence of fields
      that exceed limits to magnetic fields external to the body.

PMID- 12199556
TI  - A transmission utility's experience of applying EMF exposure standards.
AB  - Exposure standards for power-frequency electric and magnetic fields are often
      structured in terms of basic restrictions and investigation levels. For uniform
      exposures, investigation levels help the user operate within the standard without
      concern about exceeding the basic restriction. For non-uniform fields, however,
      numerical calculations of induced currents in the body may be necessary to
      determine compliance with the basic restriction. Utilities have strong incentives
      to apply exposure standards so that they do not impose unnecessary and
      unjustified constraints on their operations. They are therefore likely to be
      prepared to invest considerable effort in assessing compliance. However, the
      standards are based on round numbers, the values of tissue conductivity are not
      well characterized, and the calculations needed to apply the standards are still
      evolving. This suggests that, scientifically, this level of effort devoted to
      distinguishing compliant and non-compliant exposure scenarios is not justifiable.

PMID- 12199557
TI  - Matrix models of compartmental systems.

PMID- 12199558
TI  - Selective enrichment of low-abundance peptides in complex mixtures by elution
      modified displacement chromatography and their identification by electrospray
      ionization mass spectrometry.
AB  - Trace components were selectively enriched and detected in the tryptic digest of
      recombinant human growth hormone using elution-modified displacement
      chromatography, a hybrid technique combining features of elution and displacement
      chromatography. Based on the retention behavior of sample components in the
      elution mode, rapid and selective trace enrichment and high-resolution separation
      was achieved in a single step by utilizing appropriate combinations of an eluent
      such as aqueous acetonitrile with the displacer. Mass spectral and
      chromatographic analysis of displacement zones revealed up to 400-fold
      enhancement of the concentration of some low-abundance sample components.
      Potential application of this technique in proteomics to augment the sensitivity
      of LC-MS and 2-D gel electrophoretic approaches for the detection of biologically
      important low-abundance species is discussed.

PMID- 12199559
TI  - Application of natural receptors in sensors and assays.
AB  - Biosensors are analytical devices that use a biological or biologically derived
      material immobilized at a physicochemical transducer to measure one or more
      analytes. Although there are a large number of reviews on biosensors in general,
      there has been little systematic information presented on the application of
      natural receptors in sensor technology. This perspective discusses broadly the
      fundamental properties of natural receptors, which make them an attractive option
      for use as biorecognition elements in sensor technology. It analyses the current
      situation by reference to typical examples, such as the application of nicotinic
      acetylcholine receptor and G protein-linked receptors in affinity sensors and
      analyses the problems that need to be resolved prior to any commercialization of
      such devices.

PMID- 12199560
TI  - Molecular fluorescence, phosphorescence, and chemiluminescence spectrometry.

PMID- 12199562
TI  - Integrated microfluidic system enabling (bio)chemical reactions with on-line
      MALDI-TOF mass spectrometry.
AB  - A continuous flow micro total analysis system (micro-TAS) consisting of an on
      chip microfluidic device connected to a matrix assisted laser desorption
      ionization [MALDI] time-of-flight [TOF] mass spectrometer (MS) as an analytical
      screening system is presented. Reaction microchannels and inlet/outlet reservoirs
      were fabricated by powderblasting on glass wafers that were then bonded to
      silicon substrates. The novel lab-on-a-chip was realized by integrating the
      microdevice with a MALDI-TOFMS standard sample plate used as carrier to get the
      microfluidic device in the MALDI instrument. A novel pressure-driven pumping
      mechanism using the vacuum of the instrument as a driving force induces flow in
      the reaction microchannel in a self-activating way. Organic syntheses as well as
      biochemical reactions are carried out entirely inside the MALDI-MS ionization
      vacuum chamber and analyzed on-line by MALDI-TOFMS in real time. The
      effectiveness of the micro-TAS system has been successfully demonstrated with
      several examples of (bio)chemical reactions.

PMID- 12199561
TI  - High-throughput method for the production and analysis of large natural product
      libraries for drug discovery.
AB  - High-throughput methods were applied to the production, analysis, and
      characterization of libraries of natural products in order to accelerate the drug
      discovery process for high-throughput screening in the pharmaceutical and
      biotechnology industries. Library production integrates automated flash
      chromatography, solid-phase extraction, filtration, and high-throughput parallel
      four-channel preparative high-performance liquid chromatography to obtain the
      libraries in 96- or 384-well plates. Libraries consist of purified fractions with
      approximately one to five compounds per well. Libraries are analyzed prior to
      biological screening by a high-throughput parallel eight-channel liquid
      chromatography-evaporative light scattering detection-mass spectrometry system to
      determine the molecular weight, number, and quantity of compounds in a fraction.
      After biological screening, active fractions are rapidly purified at the
      microgram level and individual compounds are rescreened for confirmation of
      activity. Structures of active compounds are elucidated by NMR spectroscopy and
      mass spectrometry. Utilization of a novel microcoil probe allows NMR data to be
      gathered on 50 microg. As a demonstration, a library was made from the stem bark
      of Taxus brevifolia. Biological screening in the National Cancer Institute's in
      vitro panel of three cancer cell lines demonstrates that the process enables the
      discovery of active anticancer compounds not detected in the flash fractions from
      which the library originates.

PMID- 12199563
TI  - Recent advances in petroleum characterization by GC field ionization time-of
      flight high-resolution mass spectrometry.
AB  - Although mass spectrometry has been studied extensively in the past 50 years for
      analysis of petroleum and other fossil fuels, comprehensive characterization of
      total petroleum composition across a wide boiling range remains a challenge. In
      this work, we report our efforts in combining GC separation, field Ionization,
      and time-of-flight high-resolution mass spectrometry (GC-FI-TOF HRMS) for
      detailed analyses of petroleum products with a carbon number range of C6-C44. GC
      separates hydrocarbon molecules by boiling points. FI generates intact molecular
      ions for both aromatic and saturate petroleum molecules eluting from the GC. The
      elemental compositions of these molecular ions are consequently resolved and
      identified by TOF HRMS with a mass resolving power up to 7000 (M/deltaMfwhm) and
      mass accuracy of +/-3 mDa, which in turn yields chemical information
      (heteroatomic content, number of rings plus double bond, and carbon number) for
      the petroleum molecules. The ability to resolve sulfur-containing hydrocarbons is
      greatly enhanced because of the unique combination.

PMID- 12199565
TI  - Cell docking and on-chip monitoring of cellular reactions with a controlled
      concentration gradient on a microfluidic device.
AB  - We have developed a microfluidic device for on-chip monitoring of cellular
      reactions. The device consists of two primary analytical functions: control of
      cell transport and immobilization, and dilution of an analyte solution to
      generate a concentration gradient. In this device, a dam structure in parallel to
      the fluid flow was constructed for docking and alignment of biological cells,
      which allows the fragile cells to move in the microfluidic channels and to be
      immobilized with controllable numbers in desired locations. The cells docked on
      the parallel dam structure are exposed to minimal stress caused by fluidic
      pressure. Additionally, a network of microfluidic channels was designed to
      generate a concentration gradient by controlled fluid distribution and diffusive
      mixing. An analyte solution could be diluted to different gradients as a function
      of distance along the dam. We used the ATP-dependent calcium uptake reaction of
      HL-60 cells as a model for on-chip measurement of the threshold ATP concentration
      that induces significant intracellular calcium signal. The results have
      demonstrated the feasibility of using the microchip for real-time monitoring of
      cellular processes upon treatment of a concentration gradient of a test solution.
      The integration of cell manipulation and solution manipulation on a microchip
      allows the measurement of concentration-dependent biological responses within a
      confined microscale feature.

PMID- 12199564
TI  - A microfabrication-based dynamic array cytometer.
AB  - We have developed a microfabricated device for use in parallel luminescent single
      cell assays that can sort populations upon the basis of dynamic functional
      responses to stimuli. This device is composed of a regular array of noncontact
      single-cell traps. These traps use dielectrophoresis to stably confine cells and
      hold them against disrupting fluid flows. Using quantitative modeling, we have
      designed traps with a novel asymmetric extruded-quadrupole geometry. This new
      trap can be physically arrayed and electrically addressed, enabling our
      cytometer. Situating an array of these traps in a microchannel, we have
      introduced cells into the array and demonstrated observation of fluorescent
      dynamic responses followed by sorting. Such a device has potential for use in
      investigating functional processes, as revealed by temporal behavior, in large
      numbers of single cells.

PMID- 12199566
TI  - Electrochemical recognition of chiral species using quaternary ammonium
      binaphthyl salts.
AB  - The use of ephedrine-substituted quaternary ammonium binaphthyl salts as
      molecular receptors is demonstrated. The electrochemical oxidation of the
      receptor is affected by the binding of an analyte in solution. The binding site
      on the binaphthyl salt has been determined using computer modeling and confirmed
      using 1D and 2D NMR studies. It is shown that the sensitivity of the receptor is
      related to the size of the analyte. Axially chiral binaphthyl salts are shown to
      bind chiral analytes in a different manner and this is demonstrated using lactic
      and mandelic acid. The presence of a polar functional group on the analyte is
      also shown to have an effect on the guest-host interaction.

PMID- 12199567
TI  - Scanning electrochemical microscopy. 44. Imaging of horseradish peroxidase
      immobilized on insulating substrates.
AB  - Scanning electrochemical microscopy (SECM) was used to study horseradish
      peroxidase (HRP) immobilized with copolymer on insulating substrates (glass slide
      or polycarbonate membrane filter). Two methods were used to immobilize HRP: In
      the first, HRP was coimmobilized by cross-linking on a glass slide with a
      copolymer swelled in water to form a hydrogel; in the second, the same copolymer
      and avidin were coimmobilized on the glass slide and biotin-labeled HRP was
      conjugated to the avidin of the film. SECM was then used to detect the presence
      of the bound enzyme by observing the feedback current in a solution of
      benzoquinone and hydrogen peroxide, when hydroquinone was generated at the tip. A
      detection limit less than 7 x 10(5) HRP molecules within a approximately 7-microm
      diameter area was demonstrated.

PMID- 12199568
TI  - Imaging of freeze-fractured cells with in situ fluorescence and time-of-flight
      secondary ion mass spectrometry.
AB  - Bioanalytical imaging techniques have been employed to investigate cellular
      composition at the single-cell and subcellular regimes. Four imaging modes have
      been performed sequentially in situ to demonstrate the utility of a more
      integrated approach to imaging cells. The combination of bright-field, scanning
      ion, and fluorescence microscopy complements TOF-SIMS imaging of native
      biomolecules. Bright-field microscopy provides a blurred visualization of cells
      in frozen-hydrated samples, while scanning ion imaging provides a morphological
      view of freeze-fractured cells after TOF-SIMS analysis is completed. With the use
      of selective fluorescent labels, fluorescence microscopy allows single mammalian
      cells to be located in the complex ice matrix of freeze-fractured samples, a task
      that has not been routine with either bright-field or TOF-SIMS. A fluorescent
      label, DiI (m/z 834), that does not interfere with the mass spectra of membrane
      phosphatidylcholine, has been chosen for fluorescence and TOF-SIMS imaging of
      membrane phospholipids. In this paper, in situ fluorescence microscopy allows the
      distinction of single cells from ice and other sample debris, previously not
      possible with bright-field or scanning ion imaging. Once cells are located, TOF
      SIMS imaging reveals the localization of membrane lipids, even in the membrane of
      a single 15-microm rat pheochromocytoma cell. The utility of mapping lipids in
      the membranes of single cells using this integrated approach will provide more
      understanding of the functional role of specific lipids in functions of cellular
      membranes.

PMID- 12199569
TI  - Identification of cellular sections with imaging mass spectrometry following
      freeze fracture.
AB  - Freeze-fracture techniques have been used to maintain chemical heterogeneity of
      frozen-hydrated mammalian cells for static TOF-SIMS imaging. The effects the
      fracture plane has on scanning electron microscopy and dynamic SIMS images of
      cells have been studied, but the implications this preparation method has on
      static SIMS have not been addressed to date. Interestingly, the chemical
      specificity and surface sensitivity of TOF-SIMS have allowed the identification
      of unique sections of rat pheochromocytoma cells exposed to the sample surface
      during freeze fracture. Using the extensive chemical information of the fractured
      surface, cellular sections have been determined using TOF-SIMS images of water,
      sodium, potassium, hydrocarbons, phosphocholine, and DiI, a fluorescent dye that
      remains in the outer leaflet of the cell membrane. Higher amounts of potassium
      have been imaged inside a cell versus the surrounding matrix in a cross-fractured
      cell. In other fractures exposing the cell membrane, phosphocholine and DiI have
      been imaged on the outer leaflet of the cell membrane, while phosphocholine alone
      has been imaged on the inner leaflet. In this paper, we discuss how imaging mass
      spectrometry isused to uniquely distinguish three possible sections of cells
      obtained during freeze fracture. The identification of these sections is
      important in choosing cells with a region of interest, like the cell membrane,
      exposed to the surface for a more thorough investigation with imaging static TOF
      SIMS.

PMID- 12199570
TI  - Rational design of potentiometric trace level ion sensors. A Ag+-selective
      electrode with a 100 ppt detection limit.
AB  - Submicromolar to picomolar lower detection limits have recently been obtained
      with various polymer membrane ion-selective electrodes by minimizing biases due
      to ion fluxes through the membrane. For the best performance, the compositions of
      the membrane and inner solution should be optimized for each application. Given
      the number of parameters to be adjusted, it has been difficult to find the best
      parameters for a target sample. In this paper, a much simplified and more
      practical steady-state model of zero-current ion fluxes is derived, which is
      based on measurable parameters. The model allows one to predict achievable lower
      detection limits for a membrane with given selectivities. It can also be used to
      predict the optimal composition of the inner filling solution for the measurement
      of samples with a known, typical ionic background. Selectivity coefficients of
      monovalent and divalent analyte ions required for desired detection limits in
      drinking water are calculated. As an application of the proposed general recipe,
      a silver-selective electrode is developed on the basis of the ionophore O,O''
      bis[2-(methylthio)ethyl]-tert-butylcalix[4]arene. With the predicted optimal
      composition of the inner electrolyte, its lower detection limit is found to be
      10(-9) M or 100 ppt Ag+ with an ionic background of 10(-5) M LiNO3, which is very
      close to the expected value.

PMID- 12199571
TI  - Urea biosensors based on immobilization of urease into two oppositely charged
      clays (laponite and Zn-Al layered double hydroxides).
AB  - Enzyme-based field effect transistors (ENFETs) for urea determination were
      developed based on the immobilization of urease within two different clay
      matrixes, one cationic (Laponite) and the other anionic (layered double hydroxide
      (LDH)), cross-linked with glutaraldehyde. The biosensor based on the enzyme
      immobilized in Laponite shows a greater sensitivity and smaller dynamic linear
      range, because the enzymatic reaction is protected from the effect of the buffer
      capacity of the outer medium. The apparent Michaelis-Menten constant, Km(app), is
      quite similar for both biosensors. Inhibition of the enzyme by sodium tetraborate
      was investigated. Tetraborate acts as a competitive inhibitor for urease in the
      two different types of clay, the inhibitor effect being stronger for the
      LDH/urease biosensor. In particular, the maximum limit of the dynamic linear
      range extends from 1.4 mM in the absence of the inhibitor to 12 mM in the
      presence of 0.5 mM tetraborate. The Km(app) values in the presence of 0.5 mM
      tetraborate for Laponite and LDH biomembranes were 10 and 62 mM, respectively.
      Comparison of the inhibition constant values, Ki 0.16 and 0.05 mM for Laponite
      and LDH biosensors, respectively, clearly indicates a stronger enzyme-inhibitor
      interaction in the LDH/urease biomembrane.

PMID- 12199572
TI  - Square wave voltammetric detection of chemical DNA damage with catalytic poly(4
      vinylpyridine)-Ru(bpy)2(2+) films.
AB  - Reversible, catalytic films of poly(4-vinylpyridine)-Ru(bpy)2(2+) [PVP
      Ru(bpy)2(2+), bpy = 2,2'-bipyridine] on pyrolytic graphite (PG) electrodes were
      evaluated for the detection of damage to double-stranded (ds) DNA by using square
      wave voltammetry (SWV). Damage of both calf thymus and salmon testes ds-DNA in
      solution was induced by incubation of DNA at 37 degrees C with styrene oxide, the
      liver metabolite of styrene, and a suspected carcinogen. Both types of ds-DNA
      incubated in solution with saturated styrene oxide gave a linear increase in
      catalytic peak current up to 30 min, and an estimate of two damaged DNA bases in
      one thousand could be detected. The increase in catalytic current is attributed
      to better access of the catalyst redox sites to oxidizable bases in the damaged,
      partly unwound DNA. A self-contained "toxicity sensor" was also evaluated, which
      consisted of films of [PVP-Ru(bpy)2(2+)] on PG electrodes coated with films of ds
      DNA and polydiallyldimethylammonium polycations assembled layer-by-layer. These
      films also gave an increase in catalytic peak current upon incubation in
      saturated styrene oxide, and an estimate of 1 damaged base in 1000 could be
      detected. Control films or solutions of ds-DNA treated in buffer or buffer
      containing unreactive toluene resulted in no significant changes in the catalytic
      peak current with incubation time.

PMID- 12199573
TI  - Characterization of electrochemically deposited polypyrrole using magnetoelastic
      material transduction elements.
AB  - Magnetoelastic alloy films have been used as a working electrode in an
      electrochemical cell. This material allows magnetic interrogation of
      electrochemical deposition. This technique was used to monitor the
      electrochemical deposition of polypyrrole by multisweep (CV) and potentiostatic
      methods. Since the determination of the mass-sensitive magnetoelastic film's
      resonance frequency is based on magnetic transduction, an inherent advantage of
      this method is that it requires no electrical connections other than the working
      lead of the potentiostat. Increases in pyrrole deposition correlated with a
      decrease in the peak resonance frequency of the magnetoelastic alloy. This
      technique provides a novel approach by which one can monitor electrochemical
      processes.

PMID- 12199574
TI  - A chip-based electrophoresis system with electrochemical detection and
      hydrodynamic injection.
AB  - A simple capillary electrophoresis system in the planar format that uses a new,
      hydrodynamic injection principle is described. The system was realized with
      poly(dimethylsiloxane)-glass chips and microdisk electrodes for amperometric
      detection. Using a double-tee injector, no precise voltage control of the
      electrolyte reservoirs was needed, thus making the microchip CE system more user
      friendly. The analytical characteristics of chip-based CE-EC were evaluated using
      ascorbic acid as the model analyte. The reproducibility of migration time and
      signal height was expressed by relative standard deviations of 1.2% and 5.1%,
      respectively (n = 5). The limit of detection for ascorbic acid was approximately
      5 microM at a signal-to-noise ratio of 3. Practical application concerning the
      determination of physiologically relevant compounds such as noradrenaline and L
      dopa are discussed.

PMID- 12199575
TI  - Spectroscopic method for the determination of the ionic site concentration in
      solvent polymeric membranes and membrane plasticizers.
AB  - The built-in site density of either fixed sites or mobile hydrophobic ion sites
      determines whether a membrane is permselective for cations or anions of the
      sample. The molar ratio of the ionophore to the intrinsic or added ionic sites in
      an ion-selective membrane significantly influences the potentiometric response of
      ionophore-based electrodes. Consequently, full knowledge of the "site inventory"
      in an ion-selective membrane maybe essential when new, uncharacterized polymers
      or plasticizers are implemented for ion-selective electrode fabrication. A simple
      spectroscopic method was developed for the fast and accurate determination of the
      ionic site concentration (covalently attached functionalized groups or
      impurities) in plasticized polymeric membranes and membrane plasticizers. The
      method is based on the determination of the degree of protonation of hydrogen ion
      selective chromoionophores incorporated into these membranes or dissolved in the
      membrane plasticizers. In electroneutral membranes, the concentration of the
      positively charged, protonated ionophore and the total concentration of negative
      sites are equal. The method was applied for the determination of ionic sites
      (both positively and negatively charged) in PVC materials (different purity
      grade, and bearing various functional groups), polyurethanes (aliphatic,
      aromatic, and polycarbonate-based), and selected Fluka plasticizers (2
      nitrophenyl octyl ether and 2-ethylhexyl sebacate). The technique proved to be
      appropriate for fast quantification of ionic impurities in hydrophobic, optically
      transparent materials.

PMID- 12199576
TI  - Detection and identification of aqueous saccharides by using surface-enhanced
      Raman spectroscopy.
AB  - The sensitive detection and characterization of carbohydrates by means of a
      strategy based on surface-enhanced Raman spectroscopy is demonstrated. Spectra
      are obtained after injecting a small amount of saccharide solution onto a
      roughened silver substrate, with subsequent deposition of silver colloid. The
      sensitivity achieved by this two-step approach enables high-quality Raman spectra
      to be obtained for small amounts of aqueous saccharides (5 microL of a 10(-2) M
      solution) utilizing minimal laser power and small signal acquisition times (a few
      seconds). Spectral "fingerprints" obtained for seven structurally similar
      monosaccharides demonstrate clearly an effective means by which each sugar can be
      identified. The application to more complex analyses is demonstrated for
      monosaccharide mixtures and a disaccharide, whereby the SERS fingerprints aid in
      the determination of components.

PMID- 12199577
TI  - Single-pass attenuated total reflection Fourier transform infrared spectroscopy
      for the analysis of proteins in H2O solution.
AB  - The application of single-pass attenuated total reflection Fourier transform
      infrared (ATR-FT-IR) microscopy was investigated for secondary structure analysis
      of 15 representative proteins in H2O solution. This is the first reported
      application of single-pass ATR-FT-IR for protein analysis; thus, the method was
      validated using transmission FT-IR and multipass ATR-FT-IR as referee methods.
      The single-pass ATR-FT-IR technique was advantageous since the single-pass
      geometry permits rapid secondary structure analysis on small volumes of protein
      in H2O solution without the use of demountable thin path length sample cells.
      Moreover, the fact that H2O backgrounds were small allowed the simultaneous
      observation of the amide I-III, A, and B regions without having to perform H2O
      subtraction. A comparison of replicate protein spectra indicated that the single
      pass ATR-FT-IR method yields more reproducible data than those acquired by
      transmission FT-IR. The observed trends for the amide I-III and A bands obtained
      by single-pass ATR-FT-IR agreed with those in the literature for conventional
      transmission FT-IR.

PMID- 12199579
TI  - A photoinduced electron-transfer reagent for peroxyacetic acid, 4
      ethylthioacetylamino-7-phenylsulfonyl-2,1,3-benzoxadiazole, based on the method
      for predicting the fluorescence quantum yields.
AB  - To develop new photoinduced electron-transfer (PET) reagents, we established a
      method for predicting the fluorescence quantum yields (phi) of the benzofurazan
      compounds bearing an aliphatic substituent group having an n-electron. The PET
      process occurred sufficiently to reduce the phi values in the benzofurazan
      compounds bearing an aliphatic moiety, which had a high quenching ability. The
      quenching ability was estimated by the molecular orbital calculation and Stern
      Volmer plotting. The phi values of the benzofurazan compounds could be controlled
      by changing the quenching ability of a substituent group. We succeeded in
      designing a PET reagent for peroxyacetic acid (PAA), 4-ethylthioacetylamino-7
      phenylsulfonyl-2,1,3-benzoxadiazole (EPB), using the established method for
      predicting the phi values. EPB and its oxidized derivative were separated by
      reversed-phase HPLC and fluorometrically detected at 479 nm with excitation at
      362 nm. The attained detection limit for PAA was 105 fmol (S/N = 3) and the cross
      reactivity toward hydrogen peroxide was very low, indicating EPB is a highly
      sensitive and selective reagent for PAA.

PMID- 12199578
TI  - Enzymatic microreactor-on-a-chip: protein mapping using trypsin immobilized on
      porous polymer monoliths molded in channels of microfluidic devices.
AB  - Enzymatic microreactors have been prepared in capillaries and on microfluidic
      chips by immobilizing trypsin on porous polymer monoliths consisting of 2-vinyl
      4,4-dimethylazlactone, ethylene dimethacrylate, and acrylamide or 2-hydroxyethyl
      methacrylate. The azlactone functionalities react readily with amine and thiol
      groups of the enzyme to form stable covalent bonds. The optimized porous
      properties of the monoliths lead to very low back pressures enabling the use of
      simple mechanical pumping to carry out both the immobilization of the enzyme from
      its solution and the subsequent analyses of substrate solutions. The Michealis
      Menten kinetic characteristics of the reactors were probed using a low molecular
      weight substrate: N-alpha-benzoyl-L-arginine ethyl ester. The effects of
      immobilization variables such as the concentration of trypsin in solution and
      percentage of azlactone functionalities in the monolith, as well as the effect of
      reaction time on the enzymatic activity, and of process variables such as
      substrate flow velocity and residence time in the reactor, were studied in
      detail. The proteolytic activity of the enzymatic microreactor on chip was
      demonstrated at different flow rates with the cleavage of fluorescently labeled
      casein used as a substrate. The excellent performance of the monolithic
      microreactor was also demonstrated with the digestion of myoglobin at the fast
      flow rate of 0.5 microL/min, which affords a residence time of only 11.7 s. The
      digest was then characterized using MALDI-TOF MS, and 102 out of 153 possible
      peptide fragments were identified giving a sequence coverage of 67%.

PMID- 12199580
TI  - Calibration standardization algorithm for partial least-squares regression:
      application to the determination of physiological levels of glucose by near
      infrared spectroscopy.
AB  - Calibration standardization methodology for near-infrared (near-IR) spectroscopy
      is described for updating a partial least-squares calibration model to take into
      account changes in instrumental response. The guided model reoptimization (GMR)
      algorithm uses a transfer set of eight samples to characterize the new response
      and a database of previously acquired spectra used to develop the original
      calibration model. The samples in the transfer set need not have been measured
      under the old instrumental conditions, making the algorithm compatible with
      samples that change over time. The spectra comprising the transfer set are used
      to guide an iterative optimization procedure that (1) finds an optimal subset of
      samples from the original database to use in computing the updated model and (2)
      finds an optimal set of weights to apply to the spectral resolution elements in
      order to minimize the effects of instrumental changes on the computed model. The
      optimization relies on an alternating grid search and stepwise addition/deletion
      steps. The algorithm is evaluated through the use of combination region near-IR
      spectra to determine physiological levels of glucose in a synthetic biological
      matrix containing bovine serum albumin and triacetin in phosphate buffer. The
      ability to update a calibration to account for changes in the response of a
      Fourier transform spectrometer over four to six years is examined in this study.
      Separate spectral databases collected in 1994 and 1996 are used with a transfer
      set and separate test set of spectra collected in 2000. With the 1994 database,
      the standardization algorithm achieves a standard error of prediction (SEP) of
      0.69 mM for the 2000 test set. This compares favorably to SEP values > 2 mM when
      the original 1994 calibration model is used without standardization. A similar
      improvement in the prediction performance of the 2000 test set is obtained after
      standardization with the 1996 database (SEP = 0.70 mM).

PMID- 12199581
TI  - Batch-type chemiluminescence detection cell for sensitization and simplification
      of capillary electrophoresis.
AB  - A simple and convenient chemiluminescence detection cell was designed for
      capillary electrophoresis. The detection cell easily combined with capillary
      electrophoresis equipment. Luminol chemiluminescence was adapted for use with the
      detection cell. Detailed analysis and testing of the system revealed that luminol
      could be determined over a range of 2.5 x 10(-10)-6.5 x 10(-7) M (correlation
      coefficient, 0.999), with a detection limit (S/N = 3) of 2.5 x 10(-10) M (7
      amol). Furthermore, each component in a mixture of glycine, glycylglycine, and
      glycylglycylgycine, which were labeled with isoluminol isothiocyanate, was
      baseline separated and sensitively detected. Moreover, the stacking procedure was
      applied to postcolumn detection in capillary electrophoresis. When acetonitrile
      stacking was used under certain conditions in the present system,
      chemiluminescence intensities of luminol and labeled compounds were about 1 order
      of magnitude higher than those obtained without stacking. The detection limit for
      luminol was 1.5 x 10(-11) M (S/N = 3), representing the highest sensitivity of
      luminol yet reported. Finally, the effect of p-iodophenol as an enhancer of
      luminol chemiluminescence was examined under weak alkaline conditions. The
      chemiluminescence intensity of luminol was approximately 2 orders of magnitude
      higher than that in the unenhanced reaction. A preliminary immunoassay using
      horseradish peroxidase-labeled anti-mouse IgG was also developed.

PMID- 12199582
TI  - Surface modification of poly(dimethylsiloxane) microfluidic devices by
      ultraviolet polymer grafting.
AB  - Poly(dimethylsiloxane) (PDMS)-based microfluidic devices are increasing in
      popularity due to their ease of fabrication and low costs. Despite this, there is
      a tremendous need for strategies to rapidly and easily tailor the surface
      properties of these devices. We demonstrate a one-step procedure to covalently
      link polymers to the surface of PDMS microchannels by ultraviolet graft
      polymerization. Acrylic acid, acrylamide, dimethylacrylamide, 2-hydroxylethyl
      acrylate, and poly(ethylene glycol)monomethoxyl acrylate were grafted onto PDMS
      to yield hydrophilic surfaces. Water droplets possessed contact angles as low as
      45 degrees on the grafted surfaces. Microchannels constructed from the grafted
      PDMS were readily filled with aqueous solutions in contrast to devices composed
      of native PDMS. The grafted surfaces also displayed a substantially reduced
      adsorption of two test peptides compared to that of oxidized PDMS. Microchannels
      with grafted surfaces exhibited electroosmotic mobilities intermediate to those
      displayed by native and oxidized PDMS. Unlike the electroosmotic mobility of
      oxidized PDMS, the electroosmotic mobility of the grafted surfaces remained
      stable upon exposure to air. The electrophoretic resolution of two test peptides
      in the grafted microchannels was considerably improved compared to that in
      microchannels composed of oxidized PDMS. By using the appropriate monomer, it
      should be possible to use UV grafting to impart a variety of surface properties
      to PDMS microfluidics devices.

PMID- 12199583
TI  - Tandem mass spectrometry for structural characterization of proline-rich
      proteins: application to salivary PRP-3.
AB  - Proline-rich proteins (PRPs), including collagens, complement 1q, and salivary
      PRPs, are unusually difficult to sequence by mass spectrometry, due to the high
      efficiency of cleavage at the amide bond on the N-terminal of proline residues
      and the consequently low relative abundance of fragment arising from cleavages at
      other amide bonds. To fully characterize these proteins by mass spectrometry,
      specialized approaches to fragmentation are needed for the peptides with high
      proline content. Our work reported herein focused on the analysis of the set of
      peptides derived by tryptic cleavage of the salivary protein PRP-3. Two methods
      of fragmentation were compared: Collision-induced dissociation (CID) and electron
      capture dissociation (ECD). The data obtained demonstrated that ECD spectra of
      peptides containing more than 30% proline residues are simpler and easier to
      interpret than are CID spectra of those peptides. Factors that limit the two
      methods of fragmentation include the complexity of information contained in the
      CID spectra and the low efficiency of ECD processes. A complementary approach
      using both decomposition methods provides more complete and interpretable
      sequence information and yielded >93% sequence coverage for the 11-kDa PRP-3
      isolated from human saliva.

PMID- 12199584
TI  - Determination of lithium isotopic composition by thermal ionization mass
      spectrometry.
AB  - A mass spectrometric method has been proposed for the determination of the
      isotopic composition of lithium. It is based upon thermal ionization of LiOH
      loaded onto a single SiO2-coated Re filament. By this method, stable emissions of
      Li+ ion have been achieved for an extended period of time. The proposed method is
      capable of analyzing trace quantities (approximately 40 ng) of Li in the presence
      of sodium with an uncertainty of +/-0.000 25 (two standard deviations of the
      mean).

PMID- 12199585
TI  - Derivatization of ethinylestradiol with dansyl chloride to enhance electrospray
      ionization: application in trace analysis of ethinylestradiol in rhesus monkey
      plasma.
AB  - The extensive metabolism and administration of low doses of ethinylestradiol (EE)
      in preclinical animal species necessitates a sensitive analytical method to
      quantify the drug at low picogram-per-milliliter concentrations in biological
      matrixes. A highly sensitive and accurate method based on the derivatization of
      EE with dansyl chloride coupled with liquid chromatography/tandem mass
      spectrometry is described. The dansyl derivatization of EE introduced a basic
      secondary nitrogen into the molecule that was readily ionized in commonly used
      acidic HPLC mobile phases. The derivative showed an intense protonated molecular
      ion at m/z 530 under positive turbo ion spray ionization. The collision-induced
      dissociation of this ion formed a distinctive product at m/z 171, corresponding
      to the protonated 5-(dimethylamino)naphthalene moiety. The selected reaction
      monitoring, based on the m/z 530 --> 171 transition, was highly specific for EE,
      since no background signal was observed from blank plasma obtained from rhesus
      monkeys. The limit of detection, at a signal-to-noise ratio of 5, was 0.2 fg/mL
      EE spiked into blank plasma. This allowed for a lower limit of quantitation of 5
      pg/mL using a 50-microL plasma sample and 10-microL injection of dansylated
      derivative into the CTC-PAL Leap autosampler coupled to a Sciex API 4000 mass
      spectrometer. Using fast-gradient liquid chromatography, the analyte peak eluted
      at 1.6 min. The validation results showed high accuracy (% bias < 4) and
      precision (% CV < 7.5) at broad linear dynamic ranges (0.005-20 ng/mL), using
      deuterated EE as internal standard. Therefore, the facile dansyl derivatization
      coupled with tandem mass spectral analysis allowed the development of a highly
      sensitive and specific method for quantitation of trace levels of EE in the
      plasma of rhesus monkeys dosed orally and intravenously with EE.

PMID- 12199586
TI  - Resolution of 11,000 compositionally distinct components in a single electrospray
      ionization Fourier transform ion cyclotron resonance mass spectrum of crude oil.
AB  - Mass spectrometry is well-suited for complex mixture analysis, because unlike
      other types of spectroscopy, the number of mass spectral peaks per analyte is of
      order one. Here, we extend significantly the upper limit for the number of
      chemically distinct components resolved and identified in a single step.
      Specifically, electrospray selectively ionizes only the basic compounds (i.e., a
      small fraction of the entire chemical composition) in a sample of South American
      crude oil. Nevertheless, their positive ion Fourier transform ion cyclotron
      resonance mass spectrum (average mass resolving power of approximately 350,000
      from 225 to 1000 Da) contains more than 11,100 resolved peaks, of which >75% may
      be assigned to a unique elemental composition (CcHhOoNnS8). Mass scale expansion
      and graphical representations reveal increased heteroatom diversity, aromatic
      rings, and alkyl substitution with increased mass. These results set a new
      standard and illustrate the potential of high-resolution mass spectrometry for
      analysis of compositionally complex chemical mixtures.

PMID- 12199587
TI  - High-speed liquid chromatography by simultaneous optimization of temperature and
      eluent composition.
AB  - Clearly, a major trend in liquid chromatography is to increase its speed to make
      it faster. Improving throughput for routine analysis of pharmaceutical release
      samples and stability assays are all key motivations for improving separation
      speed. Recent work has focused on the theoretical benefits of temperature on
      speed in liquid chromatography. We have shown that the 5-10-fold decrease in
      eluent viscosity that comes from a temperature increase of 175 degrees C over
      ambient, and the concomitant increase in analyte diffusitivity, act to
      dramatically decrease the time needed to generate a theoretical plate. Lower
      viscosities at elevated temperatures decrease the pressure drop across the column
      and allow the use of higher linear velocities as the pump pressure limit is
      approached. Simultaneously, faster analyte diffusion at higher column temperature
      improves efficiency at high eluent velocity conditions compared to the efficiency
      at lower temperatures at the same velocity. We find that higher temperature plays
      a central role in improving speed. In this work, we show that when the percent
      organic modifier in the eluent and column temperature are adjusted to keep
      retention factors fixed, highly efficient, subminute separations can be routinely
      achieved when a hot column is used at the maximum system back pressure. We find
      that the best way to facilitate such an optimization, assuming constant
      selectivity, is to use a very retentive column so that one can work at both high
      temperature and high volume fraction of organic modifier to achieve the lowest
      possible eluent viscosity. We have also analyzed the effect that key extracolumn
      contributions have on column selection and system design.

PMID- 12199588
TI  - Regulation of protein binding toward a ligand on chromatographic matrixes by
      masking and forced-releasing effects using thermoresponsive polymer.
AB  - A novel concept of affinity regulation based on masking and forced-releasing
      effects using a thermoresponsive polymer was elucidated. Affinity chromatographic
      matrixes were prepared using either poly(glycidyl methacrylate-co-ethyleneglycol
      dimethacrylate) or poly(glycidyl methacrylate-co-triethyleneglycol
      dimethacrylate) beads immobilized with ligand molecule, Cibacron Blue F3G-A (CB),
      together with poly(N-isopropylacrylamide) (PIPAAm), a polymer with a cloud point
      of 32 degrees C. Two different lengths of spacer molecules were used for the
      immobilization of CB while maintaining the PIPAAm size constant. Chromatographic
      analyses using bovine serum albumin as a model protein showed a clear correlation
      between spacer length and binding capacity at temperatures lower than the lower
      critical solution temperature (LCST) of PIPAAm. The binding capacity under the
      LCST was significantly reduced only when the calculated spacer length was shorter
      than the mean size of the extended PIPAAm. Furthermore, the adsorbed protein
      could be desorbed (released) from the matrix surface by lowering the temperature
      to below the LCST while maintaining other factors such as pH and ion strength.
      Selective recovery of human albumin from human sera was demonstrated using this
      newly developed thermoresponsive affinity column.

PMID- 12199589
TI  - Stacking ionizable analytes in a sample matrix with high salt by a transient
      moving chemical reaction boundary method in capillary zone electrophoresis.
AB  - The paper presents a novel on-line transient moving chemical reaction boundary
      method (tMCRBM) for simply but efficiently stacking ionizable analytes in high
      salt matrix in capillary zone electrophoresis (CZE). The powerful function and
      stability of the tMCRBM are elucidated with the ionizable test analytes of L
      phenylalanine (Phe) and L-tryptophan (Trp) in the matrix with 85.6-165.6 mM
      sodium ion and further compared with the normal CZE of Phe and Trp samples
      dissolved in running buffer. The results verify that (1) the on-line tMCRBM mode
      can evidently increase separation efficiency, peak height, and resolution, (2)
      with the mode, the analytes in a 28-cm high-salt matrix plug can be stacked
      successfully and further separated well, (3) the values of relative standard
      deviation of peak height, peak area, and migrating time range from 3.9% to 6.1%;
      the results indicate the high stability of the technique of tMCRBM-CZE. The
      techniques implies obvious potential significance for those ionizable analytes,
      e.g., protein, peptide, and weak alkaline or acidic compound, in such matrixes as
      serum, urine, seawater, and wastewater, with high salt, which has a deleterious
      effect on isotachophoresis (ITP) and especially on electrostacking and field
      amplified sample injection (FASI). The mechanism of stacking of zwitterionic
      analytes in a high-salt matrix by the tMCRBM relies on non-steady-state
      isoelectric focusing (IEF) but not on transient ITP, electrostacking, and FASI.

PMID- 12199590
TI  - Enantiomer separation by countercurrent chromatography using cinchona alkaloid
      derivatives as chiral selectors.
AB  - Cinchona-derived anion-exchange-type chiral selectors have been adapted and
      employed in countercurrent chromatography (CCC) for the separation of enantiomers
      of N-derivatized amino acids and 2-aryloxypropionic acids. The accurate
      optimization of the enantioseparation in terms of solvent system composition, pH
      values, ionic strength, and CCC operating conditions was performed. A wide range
      of solvent mixtures was evaluated. Successful resolutions were achieved in
      systems such as ammonium acetate buffer/tert-amyl alcohol/methanol/heptane and
      especially ammonium acetate buffer/methyl isobutyl ketone or diisopropyl ether.
      Up to 300 mg (0.92 mmol) of N-(3,5-dinitrobenzoyl)-(+/-)-leucine was totally
      resolved in a single run using a 10 mM concentration of chiral selector in 122 mL
      of stationary phase. This amount could be increased up to 900 mg (2.77 mmol) when
      pH-zone-refining mode was applied. The results here presented account for the
      high potential of CCC as a preparative enantiomer separation technique.

PMID- 12199591
TI  - Characterization of overoxidized polypyrrole colloids imprinted with L-lactate
      and their application to enantioseparation of amino acids.
AB  - Overoxidized polypyrrole colloids imprinted with L-lactate were prepared to
      evaluate the performance of the overoxidation pseudo-template technique developed
      by the authors. A polypyrrole colloid that had been prepared from a mixture of
      monomer (pyrrole), dopant (L-lactate), steric stabilizer (poly(vinylpyrrolidone))
      and oxidizing agent (peroxodisulfate) was electrochemically overoxidized at +1.5
      V vs Ag/AgCl to create a complementary cavity for recognition of the molecules,
      which were structurally similar to dopant, through dedoping. As a target molecule
      for enantioselective uptake into the overoxidized colloid, we selected alanine,
      which is structurally different from the template (lactate) only in one side
      chain (alanine, -NH2; lactic acid, -OH). The overoxidized polypyrrole colloid
      showed higher affinity for L-alanine than for D-alanine, and an uptake ratio
      (L/D) of as high as 11 +/- 4 was observed under optimum conditions. Uptake
      reached equilibrium in 10 min, thanks to the high surface area and short
      diffusion length in the colloidal particle. Further, to confirm the
      complementarity of the cavity, the effect of side chain size on uptake of several
      alpha-amino acids was examined to indicate that the uptake amount decreased with
      increasing molecular volume of the L-amino acids.

PMID- 12199592
TI  - Insights into the cITP process using on-line NMR spectroscopy.
AB  - Recently, capillary isotachophoresis (cITP) has been coupled on-line with nuclear
      magnetic resonance (NMR) to enhance analysis of dilute charged analytes through
      sample concentration and separation. This study focuses on the unique detection
      capabilities of NMR to noninvasively examine the cITP process and obtain
      diagnostic information. With their enhanced mass sensitivity, microcoil NMR
      probes provide optimal detection for cITP/NMR. Whereas previous studies used
      deuterated buffers, a 1H NMR observable leading electrolyte, tetramethylammonium
      acetate, is employed here to better track cITP progression. Fortuitously, the 1H
      chemical shift of the acetate methyl resonance depends on pD. Hence, by using a
      calibration curve, the solution pD can be determined on-line during cITP.
      Similarly, intracapillary temperature can be measured in cITP/NMR by observing
      the HOD chemical shift. To obtain accurate chemical shift measurements, charge
      neutral tert-butyl alcohol is added to all cITP electrolyte solutions as an
      internal reference. As an ancillary benefit, line width measurements of the
      ubiquitous tert-butyl alcohol enable NMR spectral resolution to be examined
      throughout the experiment. Capable of providing quantitative results, NMR
      simultaneously determines the concentrations of the leading ion, sample, and
      counterion over the course of the cITP experiment.

PMID- 12199593
TI  - Band broadening in a microcapillary with a stepwise change in the zeta-potential.
AB  - In capillary zone electrophoresis (CZE), adsorption of charged analytes to walls
      has been observed to cause significant band broadening. The effect is believed to
      be due to modification of the flow pattern and the consequent Taylor dispersion
      caused by the alteration of the wall charge by the adsorbed analytes. Experiments
      using neutral (nonadsorbing) analytes in capillaries in which the zeta-potential
      has been deliberately altered in a controlled way by chemically coating a segment
      of the capillary have been performed by Towns and Regnier (Anal. Chem. 1992, 64,
      2473) in an effort to understand the mechanism of the band broadening. In this
      paper, the Taylor dispersion due to electroosmotic flow in such a partially
      coated capillary is calculated and compared to the experimental data. The
      theoretical predictions are found to be in excellent agreement with the data,
      thus supporting the hypothesis that the decreased resolution can be attributed to
      Taylor dispersion due to the induced pressure gradient brought about by the
      nonuniformity of the zeta-potential.

PMID- 12199594
TI  - Selective preconcentration and determination of chromium(VI) using a flat sheet
      polymer inclusion sorbent: potential application for Cr(VI) determination in real
      samples.
AB  - A method for sorption preconcentration of Cr(VI) from aqueous samples was
      developed using a polymer inclusion sorbent (PIS). The PIS used in this method
      was prepared by physical inclusion of Aliquat-336 in the matrix formed by
      cellulose triacetate and 2-nitrophenyl octyl ether. This sorbent was found to be
      stable, cost-effective, efficient for preconcentration of Cr(VI) present in the
      aqueous samples, and amenable to direct quantitative analysis of Cr(VI) held in
      it by neutron activation analysis and spectrophotometry. The quantifying of
      Cr(VI) in PIS by spectrophotometry was carried out by developing color directly
      on the PIS after reacting it with 1,5-diphenylcarbazide. The distinct color
      developed on the PIS even at very low concentrations of Cr(VI) suggests its
      possible use for field determination of Cr(VI). The composition of PIS was
      optimized to obtain maximum uptake of Cr(VI) without sacrificing uniformity in
      terms of thickness and distribution of ion-exchange sites, stability, and time
      required for quantitative sorption of Cr(VI) from aqueous samples. The Cr(VI)
      species held in the PIS, mainly HCrO4- and CrO4(2-), were found to vary as a
      function of pH of the aqueous samples from which Cr(VI) was preconcentrated. A
      close agreement was found in the abundances of Cr(VI) species held in the PIS
      with those reported in the literature for aqueous solutions at different pH. The
      variation of Cr(VI) species as a function of pH was found to have a significant
      impact on the tolerance to anions on the uptake of Cr(VI) in the PIS. The high
      selectivity of PIS toward Cr(VI) from aqueous solution at pH = 2 was explained on
      the basis of hydration of anions. The uptake of Cr(VI) was found to be fairly
      constant (88 +/- 3%) up to nearly complete exchange of counterions present in the
      PIS. The method developed in the present work was successfully used for the
      preconcentration of Cr(VI) from tap water and seawater samples containing low
      levels of Cr(VI).

PMID- 12199595
TI  - Pressurized hot water extraction with on-line fluorescence monitoring: a
      comparison of the static, dynamic, and static-dynamic modes for the removal of
      polycyclic aromatic hydrocarbons from environmental solid samples.
AB  - A comparison of the feasibility of the three operational modes of pressurized hot
      solvent extraction (PHSE) (namely, static, where a fixed extractant volume is
      used; dynamic, where the extractant continually flows through the sample; and
      static-dynamic mode, which consists of a combination of the two previous modes)
      for the extraction of polycyclic aromatic hydrocarbons (PAHs) from environmental
      solid samples (such as soil, sediment, trout, and sardine) has been performed. In
      all cases, a sodium dodecyl sulfate (SDS) aqueous solution was used as leaching
      agent. The use of a flow injection manifold between the extractor and a molecular
      fluorescence detector allowed real-time on-line fluorescence monitoring of the
      PAHs extracted from the samples, thus working as a screening system and providing
      qualitative and semiquantitative information on the target analytes extracted
      from both natural and spiked samples. The on-line monitoring option allowed the
      extraction kinetics to be monitored and the end of the leaching step to be
      determined independently of the sample matrix, thereby reducing extraction times.
      Efficiencies close to 100% have been provided by the three modes, which differ in
      the extraction time required for total removal of the target compounds. The time
      needed for the dynamic mode was shorter than that for the static mode. However,
      the establishment of a static extraction step prior to dynamic extraction was the
      key to shorten the time required for complete extraction. The method has been
      applied to a certified reference material (CRM 524, BCR, industrial
      soil/organics) for quality assurance/validation.

PMID- 12199596
TI  - Development of a direct assay for measuring intracellular AZT triphosphate in
      humans peripheral blood mononuclear cells.
AB  - Direct LC/MS/MS methods have recently been developed for measuring triphosphate
      anabolites of several nucleosidic reverse transcriptase inhibitor (NRTI) in
      peripheral blood mononuclear cells (PBMCs) from HIV-positive patients. Whereas
      AZT is one of the most-used NRTIs, no such method has been developed for AZT-TP,
      its active anabolite, mainly because of the presence of endogenous nucleotides
      that interfere with such an assay. In this paper, we first describe the
      development of two enzyme immunoassays (EIA) of AZT-TP in PBMCs: one directly
      measuring AZT-TP content; the other, measuring the nucleoside AZT after selective
      extraction of AZT-TP and dephosphorylation. The precision of these two assays was
      too low to achieve precise determination of AZT-TP in PBMC samples. Direct
      LC/MS/MS is not specific enough for AZT-TP, since at least two interfering
      endogenous nucleotides (same m/z ratio and fragment as well as retention time
      close to that of AZT-TP) are found in the intracellular medium of PBMCs. The off
      line combination of immunoaffinity extraction (IAE) and LC/MS/MS proved to be a
      successful strategy allowing without dephosphorylation appropriate specificity
      and sensitivity (limit of quantification established as 9.3 fmol/10(6) cells) to
      determine AZT-TP in PBMCs from 7 mL of blood of HIV-infected patients. Validation
      of this IAE-LC/MS/MS method demonstrated CV percent for repeatability and
      intermediate precision lower than 15%. More than 150 samples/week can be analyzed
      by one analyst, making this method suitable for routine analysis during clinical
      studies.

PMID- 12199597
TI  - Volume of pharmaceutical powders probed by frequency-domain photon migration
      measurements of multiply scattered light.
AB  - Using probability distribution analysis to describe the propagation of multiply
      scattered light between a point source and point detector located a known
      distance apart, mathematical expressions predicting the volume of sampled powder
      were determined for infinite and semi-infinite powder beds and then compared to
      experimental measurements of frequency-domain photon migration (FDPM). Our
      results show that the volume of powder sampled varies with optical properties
      and, when using FDPM techniques, with modulation frequency. For a typical
      measurement in lactose powder, the volume of powder sampled by multiply scattered
      light propagating between a 1000-microm-diameter point source and point detector
      pair separated by 8 mm is predicted to be 1.8 and 1.5 cm3 at modulated
      frequencies of 50 and 100 MHz, respectively. Experimental measurements in lactose
      powder confirm the predictions.

PMID- 12199598
TI  - High-efficiency nanoscale liquid chromatography coupled on-line with mass
      spectrometry using nanoelectrospray ionization for proteomics.
AB  - We describe high-efficiency (peak capacities of approximately 10(3)) nanoscale
      (using column inner diameters down to 15 microm) liquid chromatography
      (nanoLC)/low flow rate electrospray (nanoESI) mass spectrometry (MS) for the
      sensitive analysis of complex global cellular protein enzymatic digests (i.e.,
      proteomics). Using a liquid slurry packing method with carefully selected packing
      solvents, 87-cm-length capillaries having inner diameters of 14.9-74.5 microm
      were successfully packed with 3-microm C18-bonded porous (300-A pores) silica
      particles at a pressure of 18,000 psi. With a mobile-phase delivery pressure of
      10,000 psi, these packed capillaries provided mobile-phase flow rates as low as
      approximately 20 nL/min at LC linear velocities of approximately 0.2 cm/s, which
      is near optimal for separation efficiency. To maintain chromatographic
      efficiency, unions with internal channel diameters as small as 10 microm were
      specially produced for connecting packed capillaries to replaceable nanoESI
      emitters having orifice diameters of 2-10 microm (depending on the packed
      capillary dimensions). Coupled on-line with a hybrid-quadrupole time-of-flight MS
      through the nanoESI interface, the nanoLC separations provided peak capacities of
      approximately 10(3) for proteome proteolytic polypeptide mixtures when a positive
      feedback switching valve was used for quantitatively introducing samples. Over a
      relatively large range of sample loadings (e.g., 5-100 ng, and 50-500 ng of
      cellular proteolytic peptides for 14.9- and 29.7-microm-i.d. packed capillaries,
      respectively), the nanoLC/nanoESI MS response for low-abundance components of the
      complex mixtures was found to increase linearly with sample loading. The
      nanoLC/nanoESI-MS sensitivity also increased linearly with decreasing flow rate
      (or approximately inversely proportional to the square of the capillary inner
      diameter) in the flow range of 20-400 nL/min. Thus, except at the lower loadings,
      decreasing the separation capillary inner diameter has an effect equivalent to
      increasing sample loading, which is important for sample-limited proteomic
      applications. No significant effects on recovery of eluting polypeptides were
      observed using porous C18 particles with surface pores of 300-A versus nonporous
      particles. Tandem MS analyses were also demonstrated using the high-efficiency
      nanoLC separations. Chromatographic elution time, MS response intensity, and mass
      measurement accuracy was examined between runs with a single column (with a
      single nanoESI emitter), between different columns (same and different inner
      diameters with different nanoESI emitters), and for different samples (various
      concentrations of cellular proteolytic peptides) and demonstrated robust and
      reproducible sensitive analyses for complex proteomic samples.

PMID- 12199599
TI  - Characterization of polyesters prepared from three different phthalic acid
      isomers by CID-ESI-FT-ICR and PSD-MALDI-TOF mass spectrometry.
AB  - Polyesters prepared from the same diol, 2-butyl-2-ethyl-1,3-propanediol, but
      different phthalic acid isomers, phthalic, isophthalic, and terephthalic acid,
      were characterized by collision-induced dissociation electrospray ionization
      Fourier transform ion cyclotron resonance (CID-ESI-FT-ICR) and postsource-decay
      matrix-assisted laser desorption/ionization time-of-flight (PSD-MALDI-TOF) mass
      spectrometry. Sodiated dihydroxyl-terminated polyester oligomers containing five
      repeating units at m/z 1634 were selected as precursor ions for dissociation
      studies. Two main mechanisms occurred in the fragmentation of all of the
      polyesters, since dissociation of the oligomers was initiated by hydrogen
      rearrangement or transesterification reactions. Polyesters prepared from
      different phthalic acid isomers could be distinguished by their fragmentation
      behavior. Polyester prepared from phthalic acid was easily identified by using
      both CID-ESI-FT-ICR and PSD-MALDI-TOF mass spectrometry. However, distinguishing
      between the polyesters prepared from isophthalic and terephthalic acid succeeded
      marginally only with CID-ESI-FT-ICR mass spectrometry. Molecular dynamics
      calculations were used to obtain an idea of the fragmentation behavior of the
      polyesters. The low-energy structures of the precursor ions were determined, and
      the coordination of the oxygen atoms of the polyester oligomers to the sodium
      cation was examined more closely. Both the experimental and the theoretical
      studies showed that the sodium ion affinity of polyester changed with the
      phthalic acid isomer.

PMID- 12199600
TI  - Principles of surface-directed liquid flow in microfluidic channels.
AB  - To direct liquid flow inside microchannels, surface free energies were patterned
      by use of self-assembled monolayers (SAMs) in combination with either multistream
      laminar flow or photolithography. For the photolithographic method, two
      photocleavable SAMs were designed and synthesized. Carboxylic acid-terminated
      monolayers were obtained by photodeprotection, which was confirmed by contact
      angle and X-ray photoelectron spectroscopy. Using either of these patterning
      methods, we show that aqueous liquids flow only along the hydrophilic pathways
      when the pressure is maintained below a critical value; the liquids are referred
      to as being confined by virtual walls. Several principles of liquid flow in
      surface-patterned channels were derived analytically and verified experimentally.
      These principles include the maximum pressure that virtual walls can withstand,
      the critical width of the hydrophilic pathway that can support spontaneous flow,
      the smallest width of the liquid streams under an external pressure, the critical
      radius of curvature of turns that can be introduced into the hydrophilic pathway
      without liquid crossing the hydrophilic-hydrophobic boundary, and the minimal
      distance for two liquid streams to remain separated under the maximum pressure.
      Experimental results are in good agreement with the analytical predictions.

PMID- 12199602
TI  - Carbon nanotube scanning tunneling microscopy tips for chemically selective
      imaging.
AB  - Carboxyl-terminated single-walled carbon nanotubes (SWNTs) were successfully
      immobilized from solution phases onto the apexes of gold tips for scanning
      tunneling microscopy (STM). Gold STM tips were first modified with self-assembled
      monolayers of 4-mercaptobenzoic acid, and its carboxyl groups were used to anchor
      carboxylated SWNTs through Zn2+ ion-bridged coordination. These SWNT tips gave
      high-resolution STM images of a diether monolayer formed on the graphite surface.
      In addition and more importantly, the ether oxygens of the sample molecules were
      selectively observed as bright spots with the SWNT tips with significantly high
      reproducibility, which is due to the facilitation of electron tunneling through
      hydrogen bond interactions between the ether oxygens and carboxyl groups at the
      end of the SWNT tips.

PMID- 12199601
TI  - Potassium-selective atomic force microscopy on ion-releasing substrates and
      living cells.
AB  - A new method for simultaneous mapping of cell topography and ion fluxes was
      developed. A highly sensitive ion sensor system was generated by coating atomic
      force microscopy tips with a PVC layer containing valinomycin, an ionophore for
      potassium. The activity of specific ions was traced on artificial ion-releasing
      PVC substrates. A boundary potential was generated owing to the selective
      exchange of a specific ion between coated tip and ion-releasing substrate. The
      boundary potential was detectable as a force induced by ion-selective
      electrostatic interactions. The selectivity coefficient of valinomycin for
      potassium against sodium (K(K,Na)f) was -2.5 +/- 0.5. Potassium efflux was
      measured on living MDCK-F1 cells expressing BK(Ca) channels. We could demonstrate
      localized areas of high potassium concentrations at the cell surface. The
      potassium efflux could be reversibly inhibited by thapsigargin, which is known to
      inhibit the efflux of potassium from BK(Ca) channels by suppression of calcium
      ATPase.

PMID- 12199603
TI  - Mixing processes in a zigzag microchannel: finite element simulations and optical
      study.
AB  - A finite element model has been used in order to study the mixing process of
      species in a 100-microm-wide zigzag microchannel integrating a "Y" inlet
      junction. The distribution of the concentration was obtained by solving
      successively the Navier-Stokes equation and the diffusion-convection equation in
      the steady state form. Because of the large range of Reynolds numbers studied (1
      < Re < 800), the 2D diffusion-convection simulations are carried out with high
      diffusion coefficients. The results illustrated the effects of both flow rate and
      channel geometry on hydrodynamics and mixing efficiency. Below a critical
      Reynolds number of approximately 80, the mixing is entirely ensured by molecular
      diffusion. For higher Reynolds numbers, simulations revealed the mixing
      contribution of laminar flow recirculations. This effect increases for lower
      values of diffusion coefficients. Experimental studies on the mixing of species
      at different flow rates are reported showing the same hydrodynamic tendency.

PMID- 12199604
TI  - Elucidation of a polychlorinated bipyrrole structure using enantioselective GC.
AB  - A hexachloro congener (Q1-hex) of the natural heptachloro-1'-methyl-1,2'
      bipyrrole Q1 was recently observed as a byproduct of the Q1 synthesis. NMR
      investigation confirmed that Q1-hex has a proton on a carbon in beta-position to
      a nitrogen. Three isomers are possible that fulfill this prerequisite;
      unfortunately, however, the NMR data were not sufficient to distinguish among the
      three structural variants. Because only one isomer of Q1-hex is expected to be
      chiral, we utilized enantioselective gas chromatography and two chiral stationary
      phases to separate the atropisomers. Baseline separation of the Q1-hex
      atropisomers was obtained on 10% chemically bonded permethyl-beta-cyclodextrin.
      In the full-scan mode, it was found that Q1-hex was racemic and that both
      atropisomers had identical mass fragmentation patterns. Partial resolution of the
      Q1-hex atropisomers was obtained on 25% tert-butyldimethylsilylated beta
      cyclodextrin diluted in PS086. In concert with previous NMR data, these
      enantioseparations prove that the structure of Q1-hex is 2,3,3',4',5,5'
      hexachloro-1'-methyl-1,2'-bipyrrole (5). To our knowledge, this is the first gas
      chromatographic separation of atropisomers of an axially chiral 1,2'-bipyrrole
      derivative.

PMID- 12199605
TI  - Simultaneous multiple substrate tag detection with ESI-ion trap MS for in vivo
      bacterial enzyme activity profiling.
AB  - A bacterial identification method in which multiple enzyme activities are
      measured simultaneously and in vivo with electrospray ionization-mass
      spectrometry (ESI-MS) is described. Whole-cell bacteria are immobilized onto a
      filter support and incubated with a mixture of substrates. Each substrate is
      chosen to measure a specific enzyme activity of a targeted bacterium and to
      produce a tag of unique molecular weight. After a predetermined incubation time,
      the solution is filtered, and the supernatant consisting of a mixture of released
      tags and unhydrolyzed substrates is directly analyzed, without chromatographic
      separation, by ESI-MS. Bacteria remain viable on the filter for further analyses.
      The method was tested by measuring the aminopeptidase activity of the bacteria
      Escherichia coli, Bacillus subtilis, Bacillus cereus, and Pseudomonas aeruginosa.
      The resulting aminopeptidase enzyme profiles allowed the differentiation between
      the four bacteria tested. The method is rapid, since a multiplex advantage is
      realized when assaying for multiple enzymes, and it is amenable to automation via
      a flow injection analysis setup.

PMID- 12199608
TI  - Effect of immersion angle of a one-face sealed quartz crystal microbalance in
      liquid.
AB  - The effect of the immersion angle theta of the QCM in a liquid was investigated
      using the impedance analyzer. In the QCM, with the two faces in contact with a
      liquid, the resonant frequency shift deltaF was independent of theta and was
      dependent on only the number of faces in contact with a liquid. On the other
      hand, in the QCM, with the one face in contact with a liquid, it became clear
      that deltaF depended on theta and had the largest value at theta = 90 degrees and
      the smallest value at theta = 0 degrees. We also presented the simple model of
      deltaF in the QCM with the one face in contact with a liquid on the basis of
      experimental results.

PMID- 12199606
TI  - Partition coefficients of environmentally important phenols in a supercritical
      carbon dioxide-water system from cocurrent extraction without analysis of the
      compressible phase.
AB  - Partition coefficients of phenol, salicylic acid, and several environmentally
      important chloro- and nitrophenols in a supercritical CO2-water system were
      measured using direct cocurrent extraction of aqueous solutions of the individual
      solutes with CO2. Partitioning data on the nitrophenols and salicylic acid were
      obtained for the first time. To bypass the troublesome and error-prone analysis
      of the CO2-rich phase, the present method employed only the solute concentrations
      in the aqueous phase before and after extraction to determine the partition
      coefficient. Unlike most previous engineering studies of phenol partitioning in a
      CO2-water system, the concentrations of phenolic solutes approached infinite
      dilution in both phases. This makes the results relevant to analytical-scale SFE
      of environmental water samples with CO2. Because of effective infinite dilution
      of the solutes, the partition coefficients provide a direct measure of relative
      CO2-philicity/hydrophilicity of the individual phenols. Compared to the octanol
      water partition coefficients of substituted phenols, the CO2-water partition
      coefficients are more sensitive to substitution in the position neighboring the
      hydroxyl group.

PMID- 12199607
TI  - Functional screening of intracellular proteins in single cells and in patterned
      cell arrays using electroporation.
AB  - A tool for detection and characterization of intracellular enzyme-substrate and
      receptor-ligand interactions inside the cytoplasm of single targeted cells or
      small confined groups of cells is presented. Fluorogenic enzyme substrates and
      receptor ligands were rapidly delivered by electroosmosis and internalized by
      electroporation in cells using an electrolyte-filled capillary (EFC) biased at a
      high voltage. Specifically, alkaline phosphatase and proteases were detected in
      single NG108-15 cells using fluorescein diphosphate and casein BODIPY FL,
      respectively. The intracellular 1,4,5-inositol triphosphate (IP3) and ryanodine
      receptors were detected after EFC introduction of the selective receptor agonists
      IP3 and cyclic adenosine diphosphate ribose (cADPr), respectively. Receptor
      activation in both cases resulted in increased cytosolic concentrations of free
      calcium ions that were measured using the calcium-ion-selective probe, fluo-3.
      The effect of cADPr could be blocked by coadministration of the ryanodine
      receptor antagonist ruthenium red. Furthermore, electroporation of a plurality of
      cells grown in microwell structures (100 x 100 x 45 microm) molded in PDMS is
      demonstrated. The methods and systems described using an EFC for electroporation
      and delivery of protein markers, ligands, and substrates might be useful in high
      throughput screening of intracellular targets, with applications in proteomics
      and phenotype profiling, as well as in drug discovery.

PMID- 12199609
TI  - An eighteenth-century disease in the year 2001.

PMID- 12199610
TI  - Development of pediatric vaccine recommendations and policies.
AB  - A significant decrease in each vaccine-preventable disease has occurred since the
      introduction of the respective immunizations now included in the recommended
      childhood immunization schedule. The process through which a vaccine must travel
      from development to approval and implementation is complex. Hurdles include
      receiving approval from several advisory committees, government agencies, and
      professional organizations. At each step in the process, data regarding safety,
      immunogenicity, and efficacy are evaluated continuously and rigorously. Once a
      vaccine is approved by the Food and Drug Administration (FDA) and incorporated
      into the recommended childhood immunization schedule, continuing issues include
      those that deal with supply, safety, effectiveness, and financing. The logistics
      of development and implementation of pediatric vaccine recommendations and
      policies are reviewed.

PMID- 12199612
TI  - Hepatitis A vaccine.
AB  - Hepatitis A is an infectious disease frequently reported in the United States. An
      average of 26,000 cases were reported each year during 1980 to 1999; probably 3
      times as many occurred. Hepatitis A vaccines provide a powerful new prevention
      tool. The 2 inactivated hepatitis A vaccines available as pediatric and adult
      formulations in the United States and in many other countries are safe,
      immunogenic, and efficacious. A single dose provides excellent short-term
      protection; the second dose is thought to be important for long-term protection.
      Because hepatitis A virus (HAV) is excreted in high concentrations in the stool,
      the principal mode of transmission is person-to-person by the fecal-oral route,
      most commonly among household and sexual contacts of people with HAV infection.
      Children can be important in transmission because they frequently have
      unrecognized or asymptomatic infection. Implementation of recommendations for
      routine hepatitis A vaccination of children living in areas with consistently
      elevated hepatitis A rates appears to be resulting in dramatic declines in the
      overall incidence of the disease. Improved vaccination coverage and continued
      monitoring of incidence rates are needed to determine the overall long-term
      impact of this strategy.

PMID- 12199611
TI  - Pneumococcal vaccination of children.
AB  - Streptococcus pneumoniae is the most frequent cause of invasive bacterial
      infection in children younger than 2 years of age, reaching a peak incidence at 6
      to 12 months of age. Pneumococci also cause many cases of pneumonia, sinusitis,
      and otitis media. Incidence rates of invasive infection in children with sickle
      cell disease, acquired or congenital splenectomy, or human immunodeficiency virus
      infection are 20- to 100-fold higher than are those of healthy children during
      the first 5 years of life. Other healthy children, such as those of American
      Indian, Native Alaskan, or African American descent, also have high rates of
      invasive infection, and those children enrolled in out-of-home care may have
      modestly increased risks. Pneumococcal polysaccharide polyvalent vaccines have
      been available for more than 2 decades but are limited in their usefulness for
      children because of their inability to induce protective antibody responses in
      children younger than 2 years of age and lack of immunologic memory. In contrast,
      pneumococcal protein conjugate vaccines induce presumptive protective responses
      in infants younger than 6 months, and immunologic memory further enhances
      responses after booster doses are given. Currently, a single heptavalent
      pneumococcal protein conjugate vaccine is licensed for use in the United States
      and is recommended for routine administration to all children, beginning at 2
      months of age. It also is recommended for children between 24 and 59 months of
      age who are at high risk of acquiring invasive disease.

PMID- 12199613
TI  - Influenza vaccines in children.
AB  - Influenza is a common disease of childhood. Young children and children with high
      risk medical conditions are at increased risk of being hospitalized when infected
      with influenza virus. Children of all ages have excess physician visits and
      receive excess antibiotic prescriptions during influenza season. The safety,
      immunogenicity, and efficacy of influenza vaccines in children are described in
      this review. Clinical trials and postlicensure experience have demonstrated that
      trivalent inactivated influenza vaccine is well-tolerated in children. Efficacy
      of the inactivated vaccine also has been demonstrated in numerous clinical
      trials. In comparison to trivalent inactivated influenza vaccine, investigational
      cold-adapted, live-attenuated influenza vaccine (LAIV) has the advantage of an
      intranasal route of administration. A large clinical trial demonstrated the
      tolerability and efficacy of the trivalent live, attenuated product in children
      15 to 71 months of age. Pending information on safety and coadministration of
      this vaccine with other childhood vaccines will determine if it is licensed and
      recommended for use in children, including possible expanded indications for
      routine yearly administration to young children.

PMID- 12199614
TI  - Vaccines for the prevention of meningococcal disease in children.
AB  - Neisseria meningitidis is one of the most feared infections in pediatrics as the
      result of its rapid progression, high fatality rate, and frequent occurrence of
      sequelae. The 5 major meningococcal serogroups associated with disease are A, B,
      C, Y, and W-135. Currently available polysaccharide vaccines are effective in
      preventing disease caused by serogroups A, C, Y, and W-135 in older children and
      adults but do not elicit good long-term protection in young children. Vaccines
      that protect against serogroup B disease are still in development. As with the
      Haemophilus influenzae type b and pneumococcal polysaccharide vaccines,
      conjugation of the polysaccharide vaccine to a protein carrier dramatically
      changes vaccine characteristics, with resulting efficacy in infants. New
      meningococcal conjugate vaccines against serogroups A, C, Y, and W-135 are being
      developed. A serogroup C conjugate vaccine has been introduced successfully into
      the routine childhood schedule in the United Kingdom. New meningococcal conjugate
      vaccines are likely to have a dramatic effect on the burden of meningococcal
      disease within the next decade.

PMID- 12199615
TI  - The future of rotavirus vaccines.
AB  - In 1998, a simian-human reassortant rotavirus vaccine was licensed and
      recommended for routine use in children. Within 1 year, however, the vaccine was
      found to be a cause of intussusception, estimated to be approximately 1 case per
      10,000 immunized children, and the recommendations were withdrawn. Although the
      etiology and pathogenesis of vaccine-associated intussusception remain unclear,
      immunologic studies suggest several hypotheses. Development of new rotavirus
      vaccines necessitates the need for large, prelicensure, clinical trials to
      determine safety. Candidate vaccines currently in clinical trials include a
      bovine-human reassortant pentavalent vaccine and an attenuated human rotavirus
      monovalent vaccine. Important issues to be addressed include the acceptable, if
      any, degree of risk of developing intussusception and economic issues concerning
      the distribution of the vaccine in developing countries. The continuing interest
      of pharmaceutical companies in developing a safe and effective vaccine is
      encouraging, especially given the enormous burden of rotavirus disease in
      developing countries.

PMID- 12199616
TI  - Development of cytomegalovirus vaccines: prospects for prevention of congenital
      CMV infection.
AB  - Congenital cytomegalovirus (CMV) infection is an important cause of hearing,
      cognitive, and motor impairments that cannot be effectively prevented or treated
      by any current medical or public health interventions. A review of priorities for
      vaccine development by The Institute of Medicine of the National Academy of
      Sciences concluded that a vaccine to prevent congenital CMV infection should be a
      top priority for the United States. Evidence from clinical studies indicates that
      immunity to CMV can reduce the frequency and severity of disease. Laboratory
      investigations have identified structural and nonstructural CMV proteins that
      play a key role in eliciting protective immunity. The rationale for development
      of a CMV vaccine has been strengthened further by studies in experimental animals
      demonstrating the ability of immunization with subunit vaccines to prevent
      disease and transplacental transmission of virus. At least 4 CMV vaccines are in
      clinical trials, and advances in biotechnology are paving the way for additional
      novel vaccines.

PMID- 12199617
TI  - The science of evaluation of adverse events associated with vaccination.
AB  - All vaccines cause some adverse events; serious adverse events are rare. Causal
      associations between a vaccine and an adverse event rarely can be determined by
      specific tests such as identifying a vaccine agent in the affected tissue of
      patients. In the absence of such data, epidemiologic studies can be used to
      determine if the risk of the disorder is increased in vaccinated compared to
      unvaccinated individuals. Common mistakes include assuming a causal relationship
      based on a temporal association only or a series of affected patients. Careful
      studies have demonstrated that many hypothesized causal associations between
      vaccines and adverse events were not substantiated. False assumptions regarding
      causality are likely to occur for illnesses without a carefully defined etiology
      or pathogenesis.

PMID- 12199618
TI  - The challenge of vaccine safety.
AB  - Vaccines always will involve some risk, and risk always involves some public
      concern. Although the benefits of routine vaccination greatly outweigh any
      adverse effects, our consumer society seeks to eliminate all risk. The balance of
      risk and benefit appears to falter by the very success of preventing disease: in
      the immediate absence of the disease, the resolve to vaccinate waivers. We cannot
      expect the public to think in terms of the decision analyst and carefully weigh
      probability, risk, and benefit in a numerical fashion. In fact, the public's
      approach toward vaccination is varied and unscientific. Recognizing these
      challenges, we propose a program of continued vigilance by increasing our
      scientific base and methodology, improving vaccine safety communication through
      research and resources, maintaining a tolerance of conscientious objection as a
      safety valve for mandated routine vaccination in civilians, and calling for more
      research funding for the development of new vaccines.

PMID- 12199619
TI  - Samuel L. Katz: pioneer in development of and international advocate for
      vaccines.
AB  - Dr Samuel Katz has led an illustrious career in Pediatrics. This review
      chronicles his educational path and love of teaching, the creativity of his
      scientific approach, his outstanding performance as the beloved chairman of a
      large academic department of pediatrics, and his astonishing record both as the
      developer of vaccines at the bench and as an international advocate for
      vaccination of children. He has demonstrated a unique ability to make the world a
      better place for children and remains an inspiration to many.

PMID- 12199620
TI  - Polyunsaturated fatty acids (PUFA) and eicosanoids in human health and
      pathologies.
AB  - Linoleic and alpha-linolenic acids, obtained from plant material in the diet are
      the precursors in tissues of two families with opposing effects which are
      referred to as "essential fatty acids" (EFA): arachidonic acid (AA) and pentaene
      (eicosapentaenoic acid: EPA) and hexaene (docosahexaenoic acid: DHA) acids. The
      role of EFA is crucial, without a source of AA or compounds which can be
      converted into AA, synthesis of prostaglandins (PGs) by a cyclooxygenase (COX)
      enzyme would be compromised, and this would seriously affect many normal
      metabolic processes. COX, also known as prostaglandin endoperoxide synthase
      (Pghs) or as prostaglandin G/H synthase, is a key membrane bound enzyme
      responsible for the oxidation of AA to PGs. Two COX isoforms have been
      identified, COX-1 and COX-2 that form PGH2, a common precursor for the
      biosynthesis of thromboxane A2 (TxA2), prostacyclin (PGI2) and PGs (PGD2, PGE2,
      PGF2alpha. COX-1 enzyme is expressed constitutively in most cells and tissues.
      Its expression remains constant under either physiological or pathological
      conditions controlling synthesis of those PGs primarily involved in the
      regulation of homeostatic functions. In contrast, COX-2 is an intermediate
      response gene that encodes a 71-kDa protein. COX-2 is normally absent from most
      cells but highly inducible in certain cells in response to inflammatory stimuli
      resulting in enhanced PG release. PGs formed by COX-2 primarily mediate pain and
      inflammation but have multiple effects that can favour tumorigenesis. They are
      more abundant in cancers than in normal tissues from which the cancers arise. COX
      2 is a participant in the pathway of colon carcinogenesis, especially when
      mutation of the APC (Adenomatous Polyposis Coli) tumour suppressor gene is the
      initiating event. In addition, COX-2 up-regulation and elevated PGE2 levels are
      involved in breast carcinogenesis. It seems that there is a correlation between
      COX-2 level of expression and the size of the tumours and their propensity to
      invade underlying tissue. Inhibition by non-steroidal anti-inflammatory drugs
      (NSAIDs) of COX enzymes which significantly suppress PGE2 levels, reduced breast
      cancer incidence and protected against colorectal cancer. Therefore it is
      suggested that consumption of a diet enriched in n-3 PUFA (specifically EPA and
      DHA) and inhibition of COX-2 by NSAIDs may confer cardioprotective effects and
      provide a significant mechanism for the prevention and treatment of human
      cancers.

PMID- 12199621
TI  - Myeloma aetiology and epidemiology.
AB  - Recently there have been substantial improvements in our understanding of the
      biology of myeloma. These findings have important implications for aetiological
      studies aimed at defining the causative factors for myeloma. Myeloma is closely
      related to monoclonal gammopathy of unknown significance (MGUS), which is now
      recognized to be very common in the older population. The epidemiology of these
      conditions is presented and discussed in the context of the genetic factors
      governing both the risk of developing MGUS or of transformation to myeloma.
      Biological studies support a role for aberrant class switch recombination early
      in the natural history of myeloma suggesting that factors in the environment may
      interact with this mechanism to increase myeloma risk. Case-control and cohort
      studies have identified several known and suspected environmental exposures.
      These exposures include high doses of ionizing radiation, and occupational
      exposure in the farming and petrochemical industries. The data supporting these
      associations are presented and discussed in the context of the molecular
      mechanisms underlying these exposures. In particular DNA damage occurring as a
      consequence could readily interact with the class switch recombination process to
      increase the risk of chromosomal translocations, oncogene deregulation and
      malignant transformation. A further hypothesis, which has been extensively
      investigated, is the role of chronic immune/antigenic stimulation and the risk of
      myeloma. This concept is difficult to explain in the context of our current
      immunological concepts. The data supporting the association and how molecular
      epidemiological studies using genetic variants in cytokine genes are allowing us
      to revisit this concept are discussed in detail.

PMID- 12199622
TI  - Effect of nifedipine on the expression of p53 protein in rat gingiva.
AB  - The aim of the present study was to determine the profile of p53 protein
      expression in gingival tissues after treatment with nifedipine in rats. Rats were
      treated daily by gastric intubation with or without DMSO alone or DMSO-dissolved
      nifedipine at concentrations of 15, 30 or 60 mg/kg body weight for 1, 3 or 6
      week(s). Gingival width and height were measured macroscopically. Monoclonal
      antibodies recognizing both wild-type and mutant p53 protein were applied on
      paraffin-embedded gingival sections using microwave pretreatment and
      immunohistochemical methods. The gingival width and height were increased in the
      animals treated with nifedipine at concentrations of 30 and 60 mg/kg body weight.
      Increased gingival width and height were already seen in the animals treated with
      60 mg of nifedipine for 1 week, whereas treatments with 30 mg of nifedipine
      resulted in increased gingival width and height after treatment for at least 3
      weeks. The expression of p53 protein was elevated in the animals treated with 30
      or 60 mg of nifedipine. Treatments with nifedipine at the concentration of 60
      mg/kg body weight for 1 week induced the expression of p53 protein in the
      gingival tissues. Treatment with nifedipine in rats led to the inducement of
      gingival hyperplasia and increase in the numbers of p53-positive gingival
      epithelial cells by a dose and frequency dependent mechanism, suggesting that p53
      protein may play a crucial role in the regulation of nifedipine-induced gingival
      hyperplasia.

PMID- 12199623
TI  - Increased stiffness in common carotid artery in hyperthyroid Graves' disease
      patients.
AB  - The present study was undertaken to assess the effect of hyperthyroidism on
      stiffness in the common carotid artery (CCA) in patients with Graves' disease
      (GD) and elucidate the mechanism by which arterial stiffness is increased in
      hyperthyroidism. The arterial stiffness index beta (stiffness beta) was evaluated
      in the CCA using an ultrasonic phase-locked echo-tracking system. Stiffness beta
      was defined as the logarithm of the ratio of systolic to diastolic blood pressure
      divided by the fractional diameter increase during the cardiac cycle and thus
      established as a measure of arterial stiffness uninfluenced by the change in
      blood pressure. Seventy euthyroid GD patients were measured for CCA stiffness
      beta to determine its relationship to retinal blood flow and plasma levels of
      vascular injury markers. To investigate the effect of hyperthyroidism, 27 GD
      patients were measured for changes during antithyroid drug (ATD) therapy in
      stiffness beta and in hemodynamic parameters, retinal blood flow and plasma
      vascular injury markers. In euthyroid GD patients, stiffness beta in the CCA
      showed a significant and positive correlation with systolic blood pressure and
      pulse pressure, but not with peripheral blood flow in the central retinal artery.
      ATD therapy significantly reduced stiffness beta from 5.23 +/- 2.10 to 4.36 +/-
      1.48. The fractional reduction of stiffness beta during ATD therapy correlated
      significantly with reductions in pulse pressure and retinal blood flow, but not
      with the reductions in systolic and mean blood pressure, or any of the plasma
      injury markers. In summary, the significant increase in stiffness beta in the
      hyperthyroid state may reflect the harmful effect of hyperthyroidism on the
      arterial wall, which may in turn result from increased stroke volume.

PMID- 12199624
TI  - Preservation of myocardial energy status by bovine hemoglobin solutions during
      ischemia.
AB  - Compared to murine and human hemoglobin, bovine hemoglobin has a less exothermic
      oxygen binding and delivers oxygen even at low temperatures. This property could
      improve oxygen availability for myocytes during hypothermic arrest of hearts. The
      aim of this study was to evaluate the advantage of using cardioplegic solutions
      enriched with bovine hemoglobin when storing rat hearts. Hearts excised from rats
      after perfusion with different cardioplegic solutions (Celsior, Celsior plus 4%
      human hemoglobin, Celsior plus 4% and 8% bovine hemoglobin) were compared.
      Biopsies were obtained from the beating hearts before cardioplegic infusion and
      during a 48 h period of cold storage. Adenosine triphosphate, its catabolites and
      markers of oxidative stress were measured as indices of preservation. The results
      show that bovine hemoglobin-enriched solutions highly improve adenosine
      triphosphate content, decreasing its catabolites; no significant changes in
      antioxidant status were evident. The statistically significant difference was
      evident up to 6 h of storage. Doubling the concentration of bovine hemoglobin
      produces only slight improvement. Alternative hemoglobins with different
      properties may improve and prolong heart storage. As bovine hemoglobin delivers
      oxygen even at low temperatures, it improves energy content and anabolic
      reactions, without decreasing oxidative stress.

PMID- 12199625
TI  - The effect of high molecular weight dextran sulfate on the production of
      interleukin-8 in monocyte cell culture.
AB  - It has been demonstrated that high molecular weight dextran sulfate (HMDS) is
      involved in the activation of immune cells. We have shown that HMDS increases the
      concentration of interleukin (IL)-8 in the medium of monocyte cell culture, in a
      dose-dependent fashion, whereas under the same conditions, low molecular weight
      dextran sulfate (LMDS) does not exhibit any effect on IL-8 biosynthesis. The
      effect of HMDS on IL-8 production is additive to that of IL-1beta and tumor
      necrosis factor-a (TNFalpha). Flow cytometric analysis revealed the biosynthesis
      of IL-8 in monocytes incubated in the presence of the HMDS. We hereby postulate
      that HMDS induces IL-8 biosynthesis in monocyte cell culture.

PMID- 12199626
TI  - Regulation of elastase-type endopeptidase activity, MMP-2 and MMP-9 expression
      and activation in human dermal fibroblasts by fucose and a fucose-rich
      polysaccharide.
AB  - Tissue loss during ageing and age-dependent pathologies are the result of a
      disturbed regulation of proteolytic activities. Elastase-type endopeptidases,
      especially MMP-2 and -9, play an important role in this respect. Dermal
      fibroblast cultures and skin explant cultures were used in order to measure the
      efficiency of fucose and fucose-rich polysaccharides to downregulate the elastase
      type endopeptidase activity. Fucose and fucose-rich polysaccharides were shown to
      downregulate this elastase-type activity, the basic activity and also the
      hyaluronan or kappa-elastin-stimulated activity. In skin explant cultures, we
      could demonstrate that fucose and fucose-rich polysaccharides produced an
      inhibition of the activation of the pro-form to the active form of MMP-9. Here,
      we show that mono-, di-, oligo- and polysaccharides acting on the elastin-laminin
      receptor and/or on the fucose-mannose receptor are efficient inhibitors of such
      enzymes by downregulating elastase-type endopeptidase activity, both at the level
      of their biosynthesis and at the level of the activation of the pro-enzymes.
      Fucose and fucose-rich polysaccharide preparations were shown to be efficient
      modulators of MMP-2 and MMP-9, activity with potential therapeutic applications
      in age-related pathologies accompanied by tissue loss.

PMID- 12199627
TI  - Targeting vascular endothelial growth factor in colorectal cancer.
AB  - Recent trials have established the IFL combination (fluorouracil [5-FU],
      leucovorin, and irinotecan [CPT-11, Camptosar]) as a new standard first-line
      therapy for patients with metastatic colorectal cancer. Median survival for such
      patients treated with IFL still ranges from approximately 14 to 18 months,
      however, underscoring the need for new agents with novel mechanisms of action.
      Angiogenesis has become an attractive target for anticancer drug development,
      based on its important roles in tumor growth, invasion, and metastasis. A potent
      stimulus of angiogenesis is vascular endothelial growth factor (VEGF); two agents
      developed to inhibit VEGF activity, bevacizumab (Avastin) and SU5416, are in
      advanced clinical trials. Based on encouraging results in phase I and II trials
      with bevacizumab, a randomized trial of IFL with or without this monoclonal
      antibody is under way. Similarly, a randomized trial of 5-FU and leucovorin with
      or without the tyrosine kinase inhibitor SU5416 has recently completed accrual
      and results are pending. SU5416 is also being tested in a phase I/II trial
      combined with IFL. This article briefly reviews preclinical and clinical data
      leading to the current trials of these two agents in patients with colorectal
      cancer.

PMID- 12199628
TI  - Phase I trial of irinotecan and epirubicin in advanced cancer. Preliminary
      report.
AB  - Both irinotecan (CPT-11, Camptosar) and epirubicin (Ellence) are significant
      chemotherapeutic agents that are used in the management of many different
      cancers. Each agent works through the inhibition of topoisomerases, and
      inhibition of topoisomerases I and II may possibly result in significant clinical
      synergy. This phase I clinical study represents an investigation of the first
      combination of irinotecan and epirubicin in patients with advanced cancer.
      Standard phase I eligibility was utilized, and recruitment proceeded in cohorts
      of three with escalating doses of irinotecan and epirubicin. The treatments were
      given on days 1 and 8 of a 28-day cycle. Our initial cohort of patients developed
      significant myelosuppression that required a modification in the initial dose
      escalation scheme, and accrual to these lower doses is ongoing. Evidence of
      clinical activity has been observed. Accrual will continue until the maximum
      tolerated dose can be determined. Other schedules of the combination of
      irinotecan and epirubicin should be explored.

PMID- 12199629
TI  - Mitomycin as a modulator of irinotecan anticancer activity.
AB  - Irinotecan and mitomycin (Mutamycin) possess significant single-agent activity
      against several tumor types, and mitomycin activates topoisomerase I, the
      cellular target of irinotecan. We conducted a phase I dose-escalation study of
      irinotecan and mitomycin in 37 evaluable patients with solid tumors. Antitumor
      responses included 2 complete responses, 5 partial responses, 10 minor responses,
      and a CA 19-9 tumor marker response. Responders included 14 patients previously
      treated with chemotherapy for metastatic disease. No pharmacokinetic interaction
      between mitomycin and irinotecan was apparent when these agents were given 24
      hours apart. Responders (complete and partial responses) demonstrated the largest
      topoisomerase I induction 24 hours following mitomycin infusion. In addition,
      since maximum topoisomerase I up-regulation was reached 24 hours after
      administration of mitomycin, a delay in the administration of irinotecan after
      mitomycin appeared justified. Based on these encouraging phase I data, phase II
      clinical trials in breast and esophageal/gastroesophageal junction
      adenocarcinomas at the recommended doses and schedule are under way.

PMID- 12199630
TI  - Irinotecan in relapsed or refractory non-Hodgkin's lymphomas. Indications of
      activity in a phase II trial.
AB  - Because irinotecan (CPT-11, Camptosar) is a topoisomerase I inhibitor with a
      broad spectrum of antitumor clinical activity, we investigated its activity in
      relapsed or refractory non-Hodgkin's lymphomas (NHLs). Irinotecan at 300 mg/m2
      i.v. was administered every 21 days with intensive loperamide management of
      diarrhea. Responders received up to six treatment cycles. Of 44 registered
      patients, 32 are evaluable for response. Seventeen patients had received one
      previous regimen, and 15 patients had received two. Disease was refractory to the
      regimen preceding irinotecan in 12 patients. At baseline, serum lactate
      dehydrogenase levels were high in 47% (14/30), and beta-2-microglobulin levels
      were higher than 3.0 mg/L in 29% (8/28) of patients. Responses were seen in 12 of
      32 (38%) patients (95% confidence interval [CI] = 21%-56%). Response rates were
      43% for seven indolent (95% CI = 10%-82%), 0% for three mantle cell (95% CI = 0%
      71%), 44% for 18 relapsed aggressive (95% CI = 22%-69%), and 20% for five
      refractory aggressive NHLs (95% CI = 1%-72%). Grade 3/4 toxicities included
      myelosuppression, neutropenic fever, and diarrhea. Irinotecan appears active and
      relatively well tolerated in patients with relapsed aggressive or indolent NHL.
      Accrual to this study is continuing for better determination of response rates in
      all histologic subtypes of NHL.

PMID- 12199631
TI  - Influence of anticonvulsants on the metabolism and elimination of irinotecan. A
      North American Brain Tumor Consortium preliminary report.
AB  - The hepatic metabolism and biliary secretion of irinotecan (CPT-11, Camptosar)
      and metabolites is complex and involves cytochrome P450 isoenzymes,
      carboxylesterases, glucuronosyltransferase, and the ATP-dependent export pumps
      MRP-2 and MXR. Enzyme-inducing antiepileptic drugs (EIAEDs) such as phenytoin and
      carbamazepine are known to induce several of the metabolic pathways relevant to
      ininotecan 's elimination. The North American Brain Tumor Consortium phase I
      study is designed to determine the maximum tolerated dose and pharmacokinetics of
      irinotecan given every 3 weeks to patients who are receiving EIAEDs. The EIAEDs
      have altered both the pharmacokinetics and pharmacodynamics of irinotecan. Peak
      concentrations and the area under the plasma-time curves for both irinotecan and
      SN-38 were significantly decreased in patients receiving EIAEDs. The recommended
      phase II dose of irinotecan administered every 3 weeks is 750 mg/m2 for patients
      who have been receiving stable doses of EIAEDs.

PMID- 12199633
TI  - A conversation with Anthony R. Kovner on management research.

PMID- 12199632
TI  - Management training in long-term care.
AB  - The education of health care administrators faces its most dramatic change since
      the inception of the field. Recent discussions at the national level call for
      major overhaul of curricula and teaching modalities, including moving education
      to position students for evidence-based practice. This paper presents
      recommendations for incorporating training about chronic and long-term care into
      health care management curricula. It asserts that all health care management
      students should have a basic knowledge of the fundamental policy, operating, and
      financing principles of long-term care. The majority of people using the health
      care delivery system today, and increasingly in the future, suffer from chronic
      conditions. Long-term care services, although less expansive in structure, far
      outnumber acute care services and health plans. They will grow in the future to
      meet the portending demand. To maximize job opportunities and to optimize
      performance in any job, health care administrators need to know about the long
      term care delivery system. This paper delineates critical topics pertaining to
      long-term care, organized according to 11 fundamental management areas in which
      the field is developing core competencies. The contents were derived from a year
      long process of asking stakeholders in the various facets of long-term care what
      topics they thought were essential for administrators to know. The topics
      delineated in this document represent the consensus about essential knowledge
      that all health care administrators should have about long-term care, whether
      specializing in long-term care or following a more general management career. The
      education of health care administrators faces its most dramatic change since the
      inception ofthe field. Recent discussions at the national level call for major
      overhaul of curricula and teaching modalities, including moving education to
      position students to perform according to evidence-based practice. It is thus
      timely to consider content, as well as educational format. This paper presents
      recommendations for incorporating training about chronic and long-term care into
      health care administration curricula. It asserts that all health care
      administration students should have a basic knowledge of the fundamental policy,
      operating, and financing principles of long-term care.

PMID- 12199634
TI  - On the value of architecture and facility management in health administration
      education.
AB  - This article discusses the role and function of architecture and facility
      management in health administration education vis-a-vis an interdisciplinary set
      of courses taught in a graduate-level health administration program. These
      courses provide the future health care executive with theory and applied
      knowledge on a variety of topics. These include the history of health care
      facilities, issues in facility planning and management, principles of patient and
      staff-focused design, campus master planning, participatory methods to involve
      end users in the design of their work, and care settings. Additional skills
      acquired include an introduction to contract negotiations, the reading of
      technical documents such as blueprints, the post-occupancy assessment of
      facilities-in-use, and familiarity with future trends. Students address the topic
      of managerial ethics in relation to the built environment in some detail as a
      vehicle to illustrate the nature of key fine-grain issues of importance to the
      health administration scholar and professional. The discussion concludes with the
      presentation of a model curriculum in this subject area.

PMID- 12199635
TI  - A real-time case approach to teaching information systems in health services
      administration: hardwiring research to teaching.
AB  - The pace of change in the health policy and health administration environments
      supports the need for linking teaching and research. This article describes a
      successful effort to tap real-time synergies between faculty research on health
      care information systems development and teaching in health services
      administration. It describes the real-time case approach (RTCA), a highly
      interactive case method employed in teaching a graduate health management
      information systems course. The approach offers another alternative to the "teach
      the-text-and-lecture" model and adds important dimensions to the standard "case
      discussion" model. The article discusses the mechanics of implementing the RTCA,
      the instructor's role, and five cases used in the course. Among the benefits of
      the RTCA is that students place great reliance upon cases in interpreting other
      reading material, lectures, and discussion points in the course. Students are
      more likely to make theory connections to elements in one or more of the cases.
      Potential weaknesses include students' inhibitions to criticize and question key
      decision makers who they have met, as opposed to those who might appear in a
      fictional case. Also, some possible concession of comprehensiveness and time
      ordered treatment of information systems issues, as might be found in a written
      case study, is made in favor of the dynamics of information gathering,
      distillation, and integration by students in the real-time case environment.

PMID- 12199636
TI  - Health care partnerships in a new era.

PMID- 12199637
TI  - A new approach to assessing skill needs of senior managers.
AB  - Management of health care organizations must improve to meet the well-documented
      challenges of quality improvement and cost control. Other industries have
      developed the tools--entry education, mentoring, planned mid-career formal
      education and experience, and special programs for senior management. The purpose
      of this paper is to pilot test an alternative method to identify competencies and
      performance of health care executives. We propose using formal lists of
      technical, interpersonal, and strategic competencies and specific real events
      chosen by the respondent to identify and prioritize competencies. Results of a
      trial with 30 large health care system CEOs and 15 early careerists demonstrate
      that the method reveals useful depth and detail about managers' educational
      needs. The results suggest that current thinking about managerial education and
      learning patterns may be seriously inadequate in several respects. The continued
      improvement of U.S. health care is a pressing national concern. Quality of care
      is highly variable and substantially deficient in many institutions (Chassin and
      Galvin 1998; Committee on Quality of Health Care in America 2001). "Quality
      improvement should be the essential business strategy for healthcare in the 21st
      century (Kizer 2001)." Productivity improvements will be essential to balance
      cost pressures from an aging population and growing technology (Heffler, et al.
      2002). Skillful management is necessary to improve quality and productivity.
      Teams of dozens of caregivers are often required to improve a patient's health.
      The organizations that provide care have grown larger in response to the greater
      cost, complexity of operation and finance, and evidence of the success of scale
      in other industries. While many small professional practices, hospitals, and
      nursing homes remain, consolidation has created a few dozen provider and
      intermediary organizations exceeding a billion dollars a year in expenditures.
      These large health care organizations are, or should be, modern corporate
      organizations at least as effective as their counterparts in manufacturing,
      retailing, or finance. To achieve that goal, they will require managers with
      comparable ability, motivation, and preparation. The National Summit on The
      Future Of Health Management and Policy Education emphasized the development of
      "evidence-based management education" by identifying, prioritizing, and measuring
      mastery of specific skills, knowledge, and abilities (Griffith 2001). Faculty of
      Association of University Programs in Health Administration (AUPHA) are working
      with practitioners to identify and prioritize specific learning competencies at
      the graduate degree level. Their effort focuses on skills teachable in the
      classroom, and it is expected to lead to measured performance of graduate school
      cohorts (Griffith 2001). The purpose of this paper is to pilot test an
      alternative method to identify competencies and performance of health care
      executives. Although it deliberately draws competency elements from academic
      sources, it supplements the teachable skills approach with a questionnaire that
      asks practitioner respondents to identify the skills and knowledge necessary to
      manage a specific management event and to evaluate the performance of an
      anonymous colleague against these skills and knowledge.

PMID- 12199657
TI  - Whatever happened to shared decision-making?

PMID- 12199658
TI  - User involvement in clinical governance.
AB  - OBJECTIVES: To investigate the involvement of users in clinical governance
      activities within Primary Care Groups (PCGs) and Trusts (PCTs). Drawing on policy
      and guidance published since 1997, the paper sets out a framework for how users
      are involved in this agenda, evaluates practice against this standard and
      suggests why current practice for user involvement in clinical governance is
      flawed and why this reflects a flaw in the policy design as much as its
      implementation. DESIGN: Qualitative data comprising semi-structured interviews,
      reviews of documentary evidence and relevant literature. SETTING: Twelve
      PCGs/PCTs in England purposively selected to provide variation in size, rurality
      and group or trust status. PARTICIPANTS: Key stakeholders including Lay Board
      members (n = 12), Chief Executives (CEs) (n = 12), Clinical Governance Leads (CG
      leads) (n = 14), Mental Health Leads (MH leads) (n = 9), Board Chairs (n = 2) and
      one Executive Committee Lead. RESULTS: Despite an acknowledgement of an
      organizational commitment to lay involvement, in practice very little has
      occurred. The role of lay Board members in setting priorities and implementing
      and monitoring clinical governance remains low. Beyond Board level, involvement
      of users, patients of GP practices and the general public is patchy and
      superficial. The PCGs/PCTs continue to rely heavily on Community Health Councils
      (CHCs) as a conduit or substitute for user involvement; although their abolition
      is planned, their role to be fulfilled by new organizations called Voices, which
      will have an expanded remit in addition to replacing CHCs. CONCLUSIONS: Clarity
      is required about the role of lay members in the committees and subcommittees of
      PCGs and PCTs. Involvement of the wider public should spring naturally from the
      questions under consideration, rather than be regarded as an end in itself.

PMID- 12199659
TI  - Principles of distributive justice used by members of the general public in the
      allocation of donor liver grafts for transplantation: a qualitative study.
AB  - OBJECTIVE: To investigate the nature of public preferences in the allocation of
      donor liver grafts for transplantation. DESIGN: A qualitative study based upon
      the transcripts of four focus groups. SETTING: Derby, Derbyshire, UK.
      PARTICIPANTS: Twenty-two members of the public in the Derby locality, recruited
      to one of four focus groups through local community groups. MAIN OUTCOME
      MEASURES: The views of focus group members as to the importance (or otherwise) of
      several potential discriminating factors which could be used in the
      prioritization of patients on the waiting list for liver transplantation were
      ascertained. The factors included were expected post-transplant prognosis, the
      age of the patient, whether the patient was personally responsible for their
      illness, the time spent on the waiting list, re-transplantation or primary
      transplant and the social background of the patient. RESULTS AND CONCLUSIONS:
      Group members explored the criteria from a number of perspectives, and made some
      unexpected linkages between the criteria and wider moral principles. They did not
      come to firm conclusions about the relative desirability of the criteria, but
      their approach was notably flexible and thoughtful, with the exception of a few
      instances where they appeared to resort to arguments based on what is 'obvious'
      and 'natural'. The results of these discussions suggest that members of the
      public would be able and willing to respond positively to a more open and
      consultative system of donor liver prioritization than exists presently within
      the UK.

PMID- 12199660
TI  - Resource allocation, social values and the QALY: a review of the debate and
      empirical evidence.
AB  - Most health economists agree that public preferences should play a major role in
      setting criteria for distributing scarce resources. The quality-adjusted life
      year (QALY) is used as a preference-based measure for the outcome of health-care
      activities in health economic evaluative studies. Traditionally, health
      economists proposed maximizing the additional health gain in terms of QALYs so as
      to maximize social welfare. Evidence has grown however, that neither potential
      health gain as a single relevant determinant of value, nor the rule of maximizing
      this health gain are sufficient. Concerns about fairness and equity are also
      important to the public in distributional decisions. This paper reviews the
      debate on the role and limitations of the QALY in health-care priority setting
      and the empirical evidence surrounding it. A framework is used to systematically
      explore the available data on factors considered to be important to the public in
      health-care resource allocation, and to investigate how these fit with the
      implicit value judgements inherent in the original QALY formulation. Potential
      sources of social value are classified into (1) factors that relate to the
      characteristics of patients and (2) factors related to the characteristics of the
      intervention's effect on patients' health. As well as these main categories, the
      article considers preferences for distributional rules. Recent approaches that
      aim to capture public preferences more comprehensively and to better reflect the
      value attributed to different health-care programmes in economic evaluation
      methods are outlined briefly.

PMID- 12199661
TI  - A qualitative exploration of treatment decision-making role preference in adult
      asthma patients.
AB  - OBJECTIVES: To explore preferred treatment decision-making roles, and rationales
      for role preference, and to identify perceived facilitators to and barriers from
      attaining preferred role. DESIGN: Qualitative design. SETTING AND PARTICIPANTS:
      One secondary care and four primary care sites in North-west England. Purposive
      sample of 32 adult asthma patients with varied socio-economic backgrounds and
      disease severity. METHODS: Tape-recorded focused-conversation style interviews.
      Interview topic guide derived from the literature. Sort cards employed to provide
      the focus for exploration of role preferences. RESULTS: Active (n = 7),
      collaborative (n = 11) and passive (n = 14) decisional role preferences were
      identified. Respondents cited level of knowledge; trust; duration of condition;
      severity of condition at the decisional juncture; lifelong nature of asthma; a
      perception that 'it is my body'; characteristics of the individual and their
      response to health professionals as influencing role preference. Perceived
      facilitators and barriers to participation included condition-related knowledge,
      practical issues (e.g. lack of time during consultation) and clinicians'
      interpersonal skills. CONCLUSIONS: Most respondents wished to contribute to or
      feel involved in treatment decision-making, but not necessarily to control it.
      Some hindrances to participation would be amenable to intervention. The quality
      of the provider-patient relationship is central to facilitating participation.

PMID- 12199662
TI  - Responding to the active and passive patient: flexibility is the key.
AB  - BACKGROUND: Patients vary widely in their preferences and capacity for
      participation in medical decision-making. This study aimed to document oncologist
      responses to more extreme presentations and identify helpful and unhelpful
      strategies for clinicians. PATIENTS AND METHODS: A trained actor played the role
      of a patient with early stage breast cancer who was attending her first
      consultation with a medical oncologist. She adopted in random order two different
      consultation participation styles: that of a very anxious, active patient, and
      that of a depressed, passive patient. Medical consultations between the actor and
      16 medical oncologists were videotaped and then analysed qualitatively by two
      trained raters. RESULTS: Strategies that facilitated shared decision-making with
      both patient types and were positively endorsed by the actor/patient included
      explicit agenda-setting, active listening, checking understanding, endorsing
      question-asking, offering decisional delay, and non-verbal behaviours conveying
      empathy and warmth. Oncologists successfully negotiated with the active patient
      to share control of the consultation, and responded to emotional cues from the
      passive patient. Unhelpful strategies were also identified. CONCLUSIONS: Few
      clinicians receive training in responding to differing communication styles in
      their patients that could potentially cause conflict and hinder optimal treatment
      decision-making. This study suggests some useful strategies for oncologists to
      consider, to widen their behavioural repertoire in the cancer consultation.

PMID- 12199664
TI  - Patients' attitudes to medicines and expectations for prescriptions.
AB  - BACKGROUND: Recent research has shown that patients' expectations for
      prescriptions influence doctors' prescribing decisions, but little is known of
      the antecedents of these expectations. OBJECTIVES: To test earlier qualitative
      research about patients' views of medicines; to describe the demographic
      characteristics of those holding orthodox and unorthodox views of medicines; to
      investigate the relationship between patients' ideal and predicted expectations
      for prescriptions; and to determine the relative effects of attitudinal,
      demographic, organizational and illness variables on these expectations. DESIGN:
      Questionnaire survey of patients consulting general practitioners. SETTING AND
      PARTICIPANTS: A total of 544 patients and 15 doctors in four general practices.
      MAIN VARIABLES STUDIED: Patients' attitudes to medicines; patients' demographic
      characteristics; organizational variables; aspects of patients' presenting
      problems. OUTCOME MEASURES: Patients' ideal and predicted expectations for
      prescriptions. RESULTS: Orthodox and unorthodox attitudes to medicines can be
      measured quantitatively, and ethnicity was the only demographic variable
      associated with both. Ideal and predicted expectations for prescriptions were
      closely related to each other but differed in their antecedents. Both types of
      expectations were associated with attitudinal, demographic, organizational and
      illness variables. Ideal expectations were influenced by orthodox and unorthodox
      attitudes to medicines, while predicted expectations were only influenced by
      orthodox attitudes. CONCLUSIONS: Future studies of patients' expectations for
      health services should distinguish between ideal and predicted expectations, and
      should consider the range of possible influences on these expectations. In
      particular, the effect of the organization and context of health services should
      be investigated.

PMID- 12199663
TI  - The effect of qualitative vs. quantitative presentation of probability estimates
      on patient decision-making: a randomized trial.
AB  - BACKGROUND: Given the greater uncertainty surrounding probability estimates
      associated with qualitative (use of words or phrases) descriptions, the use of
      quantitative (numerical) information to communicate the risks and benefits of
      therapies is recommended but the impact of its use in decision aids is
      unexplored. OBJECTIVE: Using stroke prevention in atrial fibrillation as an
      example, to compare the impact of quantitative vs. qualitative descriptions of
      probability risk estimates in decision aids on the clinical decision-making
      process. DESIGN: Randomized trial with a 2 x 2 factorial design. SUBJECTS: A
      total of 198 volunteers aged 60-80 years. SETTING: Outpatient clinics of a
      university-affiliated, tertiary-care teaching hospital. METHODS: Participants
      were asked to imagine that they had atrial fibrillation, and using a decision
      aid, were then randomized to two ways of receiving pertinent risk information
      regarding the probability of stroke and major bleeding when taking warfarin,
      aspirin or no therapy: (1) quantitatively, in which the 2-year probabilities of
      stroke and major haemorrhage were presented both numerically and graphically with
      100 faces (e.g. 8 of 100), and (2) qualitatively in which these probabilities
      were presented with the use of verbal phrases (e.g. very low, moderate). OUTCOME
      MEASURES: Primary: decisional conflict. Secondary: participants' choices,
      knowledge and expectations of outcomes using qualitative and quantitative scales.
      RESULTS: Participants reviewing quantitative risk information scored better on
      the informed subscale of the decisional conflict scale (P < 0.05) and, as
      expected, were better able to estimate numerically their chance of stroke and
      bleeding when taking warfarin, aspirin or no medication. For the low risk arm,
      there were no significant differences in treatment choices for the qualitative
      and quantitative groups. For the moderate risk arm, treatment choices between the
      two groups were significantly different (P = 0.01), with those in the
      quantitative group more likely to make an actual choice and to choose therapies
      at the extremes of effectiveness (warfarin and no treatment). There were no
      significant differences between the quantitative and qualitative groups in their
      ability to rank-order their stroke risk when taking warfarin, aspirin and no
      treatment, overall knowledge about atrial fibrillation and its treatment, and
      other dimensions of decisional conflict (all P-values >0.05). CONCLUSIONS: For
      participants without the disease in question, this study found that providing
      sufficient quantitative risk information makes them feel more informed, which
      sometimes affects their treatment choices. Further studies are necessary to
      confirm these findings for patients making actual clinical decisions.

PMID- 12199665
TI  - Improving the quality of health information: the contribution of C-H-i-Q.
AB  - The quality of information should be the key driver in communicating health
      messages to the public. Staff at The Centre for Health Information Quality (C-H-i
      Q) have worked with an extensive list of partner organizations from a range of
      disciplines. These stakeholders express a desire to see improvement in the
      standards of patient information, and display a willingness to embrace new
      approaches in order to achieve change. The result is an increasingly significant
      contribution in the development of the information-exchange model of health-care,
      where the aim is to maximize public confidence in health information. Key
      activities include defining principles of quality assurance, engaging with
      stakeholders, and developing tools and training for producers and providers of
      health information.

PMID- 12199668
TI  - Guidelines for the diagnosis and management of von Willebrand disease in Italy.
AB  - von Willebrand disease (vWD) is a bleeding disorder caused by quantitative (type
      1 and 3) or qualitative (type 2) defects of von Willebrand factor (vWF). The
      molecular basis of type 2 and 3 vWD are now known and those of type 1 vWD are
      being understood. Phenotypic diagnosis is based on the measurements of plasma and
      platelet vWF, of the ability of vWF to interact with platelet receptors and the
      analysis of the multimeric structure of vWF. Due to the heterogeneity of vWF
      defects and the variables that interfere with vWF levels, a correct diagnosis of
      types and subtypes may sometimes be difficult but is very important for therapy.
      The aim of treatment is to correct the dual defects of haemostasis, i.e. abnormal
      intrinsic coagulation expressed by low levels of factor VIII (FVIII) and abnormal
      platelet adhesion. Desmopressin is the treatment of choice in patients with type
      1 vWD, who account for approximately 70% of cases, because it corrects FVIII-vWF
      levels and the prolonged bleeding time (BT) in the majority of these patients. In
      type 3 and in severe forms of type 1 and 2 vWD patients, desmopressin is not
      effective and it is necessary to resort to plasma concentrates containing FVIII
      and vWF. Treated with virucidal methods, these concentrates are effective and
      safe, but they cannot always correct BT defect. Platelet concentrates or
      desmopressin can be used as adjunctive treatments when poor correction of BT
      after plasma concentrate treatment is associated with continued bleeding.

PMID- 12199669
TI  - Efficacy and safety of a factor VIII-von Willebrand factor concentrate 8Y:
      stability, bacteriological safety, pharmacokinetic analysis and clinical
      experience.
AB  - The present study was undertaken to evaluate stability, pharmacokinetic profile
      and efficacy of continuous infusion of 8Y in patients with different types of von
      Willebrand disease (vWD). Following reconstitution, 8Y levels of von Willebrand
      factor ristocetin cofactor (vWF:Rco), vWF antigen and factor VIII coagulant
      activity (FVIII:C) decreased to about 80% of the baseline levels; addition of low
      molecular weight heparin decreased the level of FVIII:C even further.
      Reconstituted 8Y was found to be sterile for up to 6 days postreconstitution. Ten
      vWD patients (four with type 2A, three with type 3, two with type 1 and one with
      2N) underwent pharmacokinetic analysis. The recovery of vWF: RCo was
      significantly lower in patients with type 3 vWD (1.4 +/- 0.05% U(-1) kg(-1))
      compared with that of the patients with types 1 (2.3 +/- 0.52% U(-1) kg(-1)) or
      2A (2.0 +/- 0.06% U(-1) kg(-1)) vWD (P = 0.015). Type 3 vWD patients exhibited
      significantly higher vWF:RCo clearance (5.1 +/- 1.1 mL kg(-1) h(-1)) compared
      with that of patients with type 2A (2.8 +/- 0.7 mL kg(-1) h(-1)) and type 1 (2.6
      +/- 1.0 mL kg(-1) h(-1)) vWD (P = 0.028). Accordingly, terminal half-life was
      lower in patients with type 3 vWD (8.0 +/- 0.6 h(-1)) compared with type 2A (12.7
      +/- 5.9 h(-1)) or type 1 (14 +/- 1.2 h(-1)) vWD patients. Multimeric pattern of
      vWF from patients' plasma was similar to that of 8Y. In two patients treated with
      8Y by continuous infusion for prevention or treatment of bleeding haemostasis was
      achieved. Thus, 8Y is suitable and haemostatically effective for continuous
      infusion treatment in patients with vWD.

PMID- 12199670
TI  - Continuous factor VIII infusion therapy in patients with haemophilia A undergoing
      surgical procedures with plasma-derived or recombinant factor VIII concentrates.
AB  - We describe the experience of a single medical centre with continuous factor VIII
      (FVIII) infusion therapy in a cohort of patients undergoing elective surgery.
      Twenty-eight patients had a total of 45 procedures. Intraoperative haemostasis
      was considered excellent in all 45 cases. FVIII levels were maintained between
      46% and 191% of normal (median, 103%) for 2-7 days. Bleeding occurred after five
      procedures (11%) at times when factor VIII levels were within haemostatic range.
      No patient required reoperation to control bleeding. There were no cases of
      sepsis related to continuous infusion of factor VIII. We conclude that continuous
      infusion: (1) is a safe and effective means of replacement therapy in patients
      with haemophilia undergoing surgery; (2) provides easier monitoring and more
      constant coagulation factor levels; and (3) has the potential to decrease the
      cost of replacement therapy by reducing overall usage of product.

PMID- 12199671
TI  - MonoFIX-VF, a new mono-component factor IX concentrate: a single-centre
      continuous-infusion study.
AB  - MonoFIX-VF, a monocomponent factor IX concentrate, has replaced the use of
      Prothrombinex-HT as the treatment of choice for patients with factor IX
      deficiency in Australia. The haemostatic effect of MonoFIX-VF, administered by
      continuous infusion, was assessed in four subjects being treated for 10 bleeding
      episodes including five surgical procedures. MonoFIX-VF was found to be a safe
      and effective treatment for patients with haemophilia B.

PMID- 12199672
TI  - A blinded in vitro study with Refacto mock plasma samples: similar FVIII results
      between the chromogenic assay and a one-stage assay when using a higher cephalin
      dilution.
AB  - Assay of factor VIII (FVIII) in patient samples is routinely carried out using
      the one-stage assay rather than the chromogenic substrate assay. The introduction
      of new FVIII preparations for the treatment of haemophilia A, including
      immunopurified FVIII and particularly, recombinant FVIII (rFVIII) concentrates,
      has led to discrepancies between the results obtained with the two assays. In
      patients treated with rFVIII concentrates, FVIII levels measured with the one
      stage assay can be 20-50% lower than those measured with the chromogenic assay.
      In this study, the one-stage assay was performed with cephalin dilutions higher
      than those recommended by the manufacturer. B-domain-deleted recombinant FVIII,
      Refacto, was diluted to eight different concentrations, ranging from 1-100 IU dL(
      1), in FVIII-deficient plasma and the FVIII activity of the eight solutions was
      determined by the chromogenic method in a central laboratory. Aliquots were then
      assayed by the one-stage method in the four participating laboratories, using
      different dilutions of CK-Prest. When CK-Prest was reconstituted according to the
      manufacturer's recommendations (dilution 1 : 1), the difference between the one
      stage and chromogenic methods was close to 30%. CK-Prest cephalin dilutions of 1
      : 5 and 1 : 8 gave very similar results with the two methods, without increasing
      the interlaboratory coefficient of variation. These findings confirm the
      influence of phospholipids on the one-stage assay, particularly the importance of
      using a phospholipid concentration close to the physiological value in platelets.
      This modified one-stage method may therefore offer an alternative to the use of a
      concentrate-specific standard.

PMID- 12199673
TI  - Characterization of inhibitors to FVIII with an ELISA in congenital and acquired
      haemophilia A.
AB  - Different methods can be used for the detection and quantification of inhibitors
      or antibodies to coagulation factor VIII (FVIII). Traditionally, clotting assays
      have been used, in particular the Bethesda assay. These assays have, however,
      several shortcomings, due to the complex reaction kinetics of some inhibitors and
      a low sensitivity to low-titre antibodies. In addition, a universal FVIII
      inhibitor standard is lacking. Furthermore, clotting assays do not detect
      noninhibitory antibodies. Use of ELISAs has been described and FVIII from various
      commercially available FVIII concentrates has been used as target antigen in the
      assays. In the present study, we systematically explored the influence of
      different FVIII concentrates on the performance of an ELISA for detection of
      FVIII antibodies. The described ELISA was also used for further characterization
      of FVIII inhibitors in patients with acquired and congenital haemophilia A. We
      found that the source of FVIII had a substantial impact on the frequency of
      antibody detection. Albumin-free recombinant FVIII as target antigen gave the
      highest sensitivity for the assay, whereas plasma-derived concentrates containing
      a high level of von Willebrand factor (vWF) gave the lowest sensitivity.
      Presumably vWF interferes with the binding of antibodies to FVIII. We suggest
      that albumin-free recombinant FVIII should be used as target antigen when ELISAs
      are used for detection of FVIII antibodies.

PMID- 12199674
TI  - Efficacy of recombinant factor VIIa administered by continuous infusion to
      haemophilia patients with inhibitors.
AB  - We have prospectively monitored treatment of haemophilia patients with inhibitors
      by recombinant factor VIIa (rFVIIa) administered by continuous infusion to obtain
      more insight in the underlying factors of the clinical efficacy of this
      administration method. At present, 43 treatment episodes of 14 different Dutch
      haemophilia inhibitor patients are included in the database. Analysis of the data
      showed a discrepancy between the efficacy of rFVIIa continuous infusion treatment
      of acute and surgical bleeds in the oral cavity [one (14%) effective, two (29%)
      partially effective, four (57%) not effective] and other parts of the body [29
      (80%) effective, four (11%) partially effective, two (6%) not effective, one (3%)
      impossible to classify]. Patients who had acute or surgical oral cavity bleeds,
      uncontrolled by rFVIIa continuous infusion, reacted favourably to rFVIIa
      continuous infusion in other locations of the body. Acute bleeding episodes in
      the oral cavity, which could not be controlled by rFVIIa continuous infusion,
      stopped when the treatment regimen was switched to rFVIIa bolus injections.
      Finally, haemostatic control during dental extractions was excellent after the
      initial rFVIIa bolus injection preceding the continuous infusion, but rebleeds
      occurred in all patients within 48 h under rFVIIa continuous infusion coverage.
      These observations suggest that the efficacy of rFVIIa continuous infusion
      depends, at least in part, on the location of the body in which the bleeding
      occurs and that rFVIIa bolus injections are more effective than rFVIIa continuous
      infusion in the oral cavity. We hypothesize that the inability of rFVIIa
      continuous infusion treatment to sufficiently inhibit fibrinolysis is the
      underlying cause of the decreased efficacy of rFVIIa continuous infusion
      treatment in the oral cavity.

PMID- 12199675
TI  - Breastfeeding does not influence the development of inhibitors in haemophilia.
AB  - Our aim was to test the hypothesis that breastfeeding may reduce development of
      inhibitors in male infants with haemophilia by inducing an oral immune tolerance
      to factor VIII. To achieve that goal, we performed a structured epidemiological
      survey comprising all males born with severe haemophilia A (in all 100 patients,
      19 with inhibitors) or haemophilia B (in all 16 patients, six with inhibitors) in
      Sweden in 1980-99. Our results show no protective effect of breastfeeding.

PMID- 12199676
TI  - Factors predictive of death among HIV-uninfected persons with haemophilia and
      other congenital coagulation disorders.
AB  - Historically, the leading cause of death among persons with haemophilia and other
      congenital coagulation disorders was uncontrolled bleeding. Mortality was
      associated with severe deficiency of coagulation factors VIII or IX and
      especially with high-titre antifactor neutralizing antibodies (inhibitors). The
      catastrophic contamination of plasma donor pools with human immunodeficiency
      virus (HIV) resulted in acquired immunodeficiency syndrome replacing haemorrhage
      as the leading cause of death among persons with haemophilia. Rather little has
      been written, however, about mortality among those not infected with HIV. The
      objective of this study was to identify conditions associated with all-cause
      mortality among HIV-uninfected patients who were followed for a mean of 8.8 years
      in the Multicentre Hemophilia Cohort Study. Among the 364 children (mean age 8
      years), there were four deaths; two related to cancer, one to trauma, and the
      fourth to haemorrhage, end-stage liver disease and sepsis. Among the 387 HIV
      uninfected adults (mean age 35 years) there were 29 deaths, with haemorrhage the
      leading cause of death, followed by hepatic, stroke and cancer deaths. Prognostic
      factors for all-cause mortality among the adults included haemophilia Type A with
      neutralizing antibodies [age-adjusted relative rate (RR) 3.1, 95% confidence
      interval (CI) 1.4-6.9] and serologic evidence of both hepatitis B and C virus (RR
      4.1, 95% CI 0.97-17.6). Although hepatitis C viral load was slightly lower in
      patients with hepatitis B virus surface antigenaemia, it was unrelated to vital
      status. We conclude that causes of death and prognostic factors for current HIV
      uninfected haemophilia patients are similar to those noted before the HIV
      epidemic. Better understanding, prevention and control of neutralizing antibodies
      and hepatitis infections may substantially improve longevity for people with
      haemophilia.

PMID- 12199677
TI  - Significance of immune status, genotype and viral load in the severity of chronic
      hepatitis C in HIV infected haemophilia patients.
AB  - Chronic hepatitis C is associated with more severe liver disease in patients
      coinfected with HIV, but the pathogenic mechanism of this more aggressive course
      is still unclear. The aim of this study was to assess the relationship of HCV
      genotype, viral load and epidemiological factors with the histological severity
      of chronic hepatitis in haemophilia patients with HCV/HIV coinfection, taking
      into consideration the immune status of the patients. Twenty-one HIV/HCV
      coinfected haemophilia patients, with mean age +/- SD 35.7 +/- 8.7 years,
      underwent transcutaneous liver biopsy 6-15 years (median 12 years) after HIV and
      6-32 (median 21.5 years) years after HCV infection. Twelve patients were stage A
      (CDC), six stage B and three stage C. CD4 cells were < 50 microL(-1) in three
      patients (14.3%), 50-200 in 11(52.4%) and > 200 in 7(33.3%). Mean +/- SD log(10)
      HCV-RNA was 6.87 +/- 0.7 copies mL(-1) (range 5.4-7.9), and mean +/- SD log(10)
      HIV-RNA was 3.75 +/- 0.98 copies mL(-1) (range 2.7-6), at the time of liver
      biopsy. Minimal hepatitis was diagnosed in five patients (24%), mild in 10 (48%)
      and moderate in six (28%). Hepatitis stage 0-2 was found in seven cases (33%) and
      cirrhosis in six (29%). Statistical analysis showed a significant association of
      CD4 count < 50 with minimal hepatitis and of CD > 200 with mild and moderate
      hepatitis (P = 0.033). In addition, minimal hepatitis was found only in patients
      with stage C, while the majority of subjects with HIV stage A showed mild and
      moderate hepatitis (P = 0.003). Moreover genotype 1 was independently associated
      with advanced hepatitis stage (P = 0.04). No relationship was found between
      hepatitis severity, HIV or HCV RNA levels, patient's age and duration of HIV or
      HCV infection. Our results suggest that HCV/HIV coinfection may aggravate the
      course of hepatitis in the phase of immunocompetence, most probably through an
      immune mediated process. Genotype 1 seems to be associated with advanced liver
      disease.

PMID- 12199678
TI  - Cost related to replacement therapy during hospitalization in haemophiliacs with
      or without inhibitors: experience of six French haemophilia centres.
AB  - Replacement therapy in haemophiliacs has a major economic impact on health
      establishments. We assessed in this prospective study the cost of clotting factor
      concentrate therapy for haemophilia A or B patients. We compared the overall
      costs of treated patients with or without inhibitors. In six French haemophilia
      centres, 278 consecutive hospitalizations were collected and analysed between
      June 97 and June 99. Haemophilia must be considered as the main cost factor
      during hospitalization. The severity of bleeds and surgical procedures increase
      the total cost. Furthermore, the daily and total costs are closely linked to the
      presence or the absence of inhibitors. This study should enable the hospital
      administration to evaluate the necessary resources to the clotting factor therapy
      in haemophiliacs with or without inhibitors during hospitalization.

PMID- 12199679
TI  - Assessment of the carrier status by pedigree analysis in some families from
      India.
AB  - Pedigree analysis is an important tool to assess the carrier status of the
      females in the families of haemophiliac patients. A study was conducted on 85
      families, of which 75 were of haemophilia type A and 10 of haemophilia type B.
      The probability values of the females being carriers were calculated by the
      Bayesian method. The results revealed that 45 mothers were genetic obligate
      carriers and the remaining 40 probable, hence the transmission was of familial
      nature in 45 families, whereas the remaining 40 were categorized as isolated
      cases. The probability values of 425 females were calculated and a wide range of
      probability values ranging from 0.0295 to 1 was observed.

PMID- 12199680
TI  - Haemostasis: from bench to bedside.

PMID- 12199681
TI  - Anti-inhibitor coagulant complex for the rescue therapy of acquired inhibitors to
      factor VIII: case report and review of the literature.
AB  - A 62-year-old African-American man with a history of hypertension, asthma, and
      prostate cancer, but no prior history of haemophilia presented with gross
      haematuria following a motor vehicle accident. Coagulation studies revealed a
      prolonged partial thromboplastin time. Subsequent mixing study and factor
      analysis confirmed factor VIII (FVIII) deficiency. The patient subsequently
      developed a knee haemarthrosis associated with persistent haematuria and a
      profoundly elevated FVIII inhibitor titre. Fresh frozen plasma was initiated upon
      presentation. Once FVIII inhibitor was discovered, immunosuppressive agents were
      started. Concurrent treatment with acute bypass agents including porcine FVIII,
      and recombinant human factor VIIa (rFVIIa;NovoSeven), was also given. Ultimately,
      anti-inhibitor coagulant complex (Autoplex T) was administered, stabilizing the
      haematuria and haemarthrosis. There was no additional bleeding 6 months after the
      last dose of anti-inhibitor coagulant complex. This case is consistent with
      others in which anti-inhibitor coagulant complex therapy was used successfully to
      manage patients with serious acute bleeding problems who are found to have
      acquired inhibitors to factor VIII.

PMID- 12199682
TI  - Two patients with haemophilia and acute leukaemia.
AB  - Acute leukaemia is the commonest form of malignancy in childhood. The
      coincidental development of leukaemia in children or adults with haemophilia is
      extremely rare, although cases of leukaemia and other malignancies have been
      reported previously in HIV-positive subjects. Of a total of 440 people with
      haemophilia registered with our society, two were diagnosed with acute leukaemia
      last year. The development of leukaemia in a subject with haemophilia has
      previously been reported from our country in 1985, but the negative HIV status of
      these recent cases is very interesting. The first case involved a 14-year-old boy
      with moderate haemophilia A, who developed acute lymphoblastic leukaemia (ALL)
      [French-American-British (FAB) classification L2]. The second subject was a 16
      year-old boy who had moderately severe haemophilia A with no previous family
      history, and developed acute nonlymphocytic (myelomonocytic) leukaemia (FAB-M4).
      Both patients received conventional chemotherapy and this report discusses the
      potential problems in management of such cases, including diagnosis and
      administration of chemotherapy in subjects with a pre-existing haemorrhagic
      disorder. Extensive cutaneous and mucosal bleeding, as well as bleeds in joints
      previously affected by haemarthrosis and alterations of haematological values
      were all initially suggestive of the development of inhibitors against factor
      VIII, but the appearance of blasts in the peripheral blood and bone marrow led to
      the definitive diagnosis. The risk of bleeding, due to the combination of both
      leukaemia and the consequences of the chemotherapy, was overcome by the
      administration of coagulation factor concentrates (daily initially followed by
      prophylactic doses after successful induction of remission in both patients). The
      young patient with ALL is now receiving the maintenance phase of the Children's
      Cancer Study Group 1961 protocol and is in the 15th month of follow-up, without
      any complications. The other case relapsed in the seventh month, developing
      enterobacter sepsis, and died. An important lesson to be learnt from these cases
      is that the possible diagnosis of leukaemia should not be overlooked in a patient
      with haemophilia and severe haemorrhagic problems, if the first-line differential
      diagnosis of inhibitor development against factor VIII (or IX) has been excluded.

PMID- 12199683
TI  - Unusual presentation of factor XIII deficiency.
AB  - Factor XIII deficiency is a rare inherited bleeding disorder that is often
      difficult to diagnose. The standard screening tests are normal in these patients
      and their bleeding phenotype may be variable. We report the case of a 3-year-old
      girl who presented with an intracranial haemorrhage. Several confounding factors,
      such as the suspicion of an arteriovenous malformation and the development of a
      deep venous thrombosis, led to a delay in the diagnosis of factor XIII
      deficiency. Subsequently, her brother was also found to have severe factor XIII
      deficiency. This case highlights the importance of a detailed history and of
      screening families in which index cases have been identified. It should also
      remind physicians that bleeding disorders may have unusual presentations and
      should be sought when investigating unexplained bleeding.

PMID- 12199684
TI  - Approaches to successful total knee arthroplasty in haemophilia A patients with
      inhibitors.

PMID- 12199685
TI  - Desmopressin is not always effective in mild haemophilia A patients undergoing
      urological surgery: the need of standardized protocols.
AB  - Desmopressin may be an efficient haemostatic treatment for mild A haemophiliacs
      because its infusion raises plasma factor VIII level. We report the use of
      desmopressin in five mild haemophilia A patients undergoing urological surgery.
      They all received a preoperative infusion (0.3 microg kg(-1), i.v.) 1 h before
      incision followed by repeated injections at 12- or 24-h intervals according to
      the severity of the procedure. Nevertheless, four patients presented a
      postoperative bleeding requiring again surgery performed for 3 of them under
      clotting factor concentrate instead of desmopressin. The occurrence of
      haemorrhage was not always correlated with particularly low plasma factor VIII
      level. Surgical management of urological procedures with desmopressin in mild
      haemophilia A patients requires standardized protocols.

PMID- 12199686
TI  - Three novel point mutations causing haemophilia A.
AB  - Haemophilia A is an X-linked bleeding disorder caused by mutations in the factor
      VIII gene. In our efforts to elucidate molecular defects in the haemophilia A
      patients from the Republic of Macedonia, we employed nonradioactive single-strand
      conformation polymorphism analysis followed by direct sequencing, for identifying
      point mutations in the factor VIII gene. In the present study we report the
      detection of three novel missense mutations: Met19 --> Arg; Ala78 --> Pro and
      Cys2174 --> Gly, all causing haemophilia A.

PMID- 12199687
TI  - Life-threatening haemorrhage from a gastric Dieulafoy lesion in a child with
      haemophilia.

PMID- 12199688
TI  - Radial artery mycotic pseudoaneurysm in a haemophiliac: a potentially fatal
      complication of arterial catheterization.
AB  - We present a case of radial artery pseudoaneurysm formation in a haemophiliac
      patient, which developed after radial artery cannulation. Haematologists and
      anaesthetists should be aware of this potentially fatal condition.

PMID- 12199690
TI  - Haemophilia prophylactic treatment in Spain.

PMID- 12199689
TI  - Haemorrhage into a popliteal cyst: an unusual complication of haemophilia A.
AB  - A 7(1/2)-year-old boy with severe haemophilia A had increasing discomfort and
      pain in his left knee after sledding on ice and landing on his knees. Left knee
      pain persisted for days despite recombinant factor VIII replacement. Imaging
      studies showed that by day 10 a popliteal cyst had ruptured, with diffusion of
      blood into the calf muscles. This case illustrates another possible bleeding
      complication in patients with a bleeding disorder and a popliteal cyst.

PMID- 12199691
TI  - Mutation analysis is an essential strategy in the genetic counselling of sporadic
      haemophilia B families.

PMID- 12199693
TI  - Insufficient hydrogen-bond desolvation and prion-related disease.
AB  - A structuring and eventual exclusion of water surrounding backbone hydrogen bonds
      takes place during protein folding as hydrophobic residues cluster around such
      bonds. Taken as an average over all hydrogen bonds, the extent of desolvation is
      nearly a constant of motion, as revealed by re-examination of the longest all
      atom trajectory with explicit solvent [Y. Duan & P. A. Kollman (1998) Science
      282, 740]. Furthermore, this extent of desolvation is preserved across native
      soluble proteins, except for cellular prion proteins. Thus, a physico-chemical
      picture of prion-related disease emerges. The epitope for protein-X binding, the
      region undergoing vast conformational change and the trigger and locker for this
      change are inferred from the location of under-desolvated hydrogen bonds in the
      cellular prion protein.

PMID- 12199694
TI  - Identification and localization of glycine in the inner core lipopolysaccharide
      of Neisseria meningitidis.
AB  - The amino acid glycine is identified as a component of the inner core
      oligosaccharide in meningococcal lipopolysaccharide (LPS). Ester-linked glycine
      residues were consistently found by mass spectrometry experiments to be located
      on the distal heptose residue (HepII) in LPS from several strains of Neisseria
      meningitidis. Nuclear magnetic resonance studies confirmed and extended this
      observation locating the glycine residue at the 7-position of the HepII molecule
      in L3 and L4 immunotype strains.

PMID- 12199695
TI  - De-regulation of D-3-phosphoglycerate dehydrogenase by domain removal.
AB  - Escherichia coli 3-phosphoglycerate dehydrogenase (PGDH) catalyzes the first step
      in serine biosynthesis, and is allosterically inhibited by serine. Structural
      studies revealed a homotetramer in which the quaternary arrangement of subunits
      formed an elongated ellipsoid. Each subunit consisted of three domains:
      nucleotide, substrate and regulatory. In PGDH, extensive interactions are formed
      between nucleotide binding domains. A second subunit-subunit interaction occurs
      between regulatory domains creating an extended beta sheet. The serine-binding
      sites overlap this interface. In these studies, the nucleotide and substrate
      domains (NSDs) were subcloned to identify changes in both catalytic and physical
      properties upon removal of a subunit-subunit interface. The NSDs did not vary
      significantly from PGDH with respect to kinetic parameters with the exception
      that serine no longer had an effect on catalysis. Temperature dependent dynamic
      light scattering (DLS) revealed the NSDs aggregated > 5 degrees C before PGDH,
      indicating decreased stability. DLS and gel filtration studies showed that the
      truncated enzyme formed a tetramer. This result negated the hypothesis that the
      removal of the regulatory domain would create an enzyme mimic of the unregulated,
      closely related dimeric enzymes. Expression of the regulatory domain, to study
      conformational changes induced by serine binding, yielded a product that by CD
      spectra contained stable secondary structure. DLS and pulsed field gradient NMR
      studies of the regulatory domain showed the presence of higher oligomers instead
      of the predicted dimer. We have concluded that the removal of the regulatory
      domain is sufficient to eliminate serine inhibition but does not have the
      expected effect on the quaternary structure.

PMID- 12199696
TI  - NMR and MS evidences for a random assembled O-specific chain structure in the LPS
      of the bacterium Xanthomonas campestris pv. Vitians. A case of unsystematic
      biosynthetic polymerization.
AB  - Xanthomonas campestris pv. vitians is a Gram-negative plant-associated bacterium
      that acts as causative agent of bacterial leaf spot and headrot in lettuce. The
      lipopolysaccharide of this bacterium is suspected to be an important molecule for
      adhesion to and infection of the plants. The lipopolysaccharide has been isolated
      from the phenol phase and the O-specific chain characterized by compositional
      analysis, high field NMR and MALDI-TOF MS. It consists of a nonrepetitive
      branched polysaccharide with a rhamnan backbone to which Fuc3NAc is linked. The
      NMR and MS approach led to the characterization of the fine structure of the
      polymer, which is randomly assembled. The rhamnan backbone is built up of beta
      Rhap and alpha-Rhap, this last is present in one, two or three adjacent units and
      branched by an alpha-Fucp3NAc unit. This is a real case of a random constituted O
      specific chain, therefore biosynthetic studies towards the comprehension of this
      irregular biosynthesis are needed.

PMID- 12199697
TI  - A structural basis for the pH-dependence of cofilin. F-actin interactions.
AB  - A marked pH-dependent interaction with F-actin is an important property of
      typical members of the actin depolymerizing factor (ADF)/cofilin family of
      abundant actin-binding proteins. ADF/cofilins tend to bind to F-actin with a
      ratio of 1 : 1 at pH values around 6.5, and to G-actin at pH 8.0. We have
      investigated the mechanism for the pH-sensitivity. We found no evidence for pH
      dependent changes in the structure of cofilin itself, nor for the interaction of
      cofilin with G-actin. None of the actin-derived, cofilin-binding peptides that we
      had previously identified [Renoult, C., Ternent, D., Maciver, S.K., Fattoum, A.,
      Astier, C., Benyamin, Y. & Roustan, C. (1999) J. Biol. Chem. 274, 28893-28899]
      bound cofilin in a pH-sensitive manner. However, we have detected a
      conformational change in region 75-105 in the actin subdomain 1 by the use of a
      peptide-directed antibody. A pH-dependent conformational change has also been
      detected spectroscopically in a similar peptide (84-103) on binding to cofilin.
      These results are consistent with a model in which pH-dependent motion of
      subdomain 1 relative to subdomain 2 (through region 75-105) of actin reveals a
      second cofilin binding site on actin (centered around region 112-125) that allows
      ADF/cofilin association with the actin filament. This motion requires salt in
      addition to low pH.

PMID- 12199698
TI  - Swollenin, a Trichoderma reesei protein with sequence similarity to the plant
      expansins, exhibits disruption activity on cellulosic materials.
AB  - Plant cell wall proteins called expansins are thought to disrupt hydrogen bonding
      between cell wall polysaccharides without hydrolyzing them. We describe here a
      novel gene with sequence similarity to plant expansins, isolated from the
      cellulolytic fungus Trichoderma reesei. The protein named swollenin has an N
      terminal fungal type cellulose binding domain connected by a linker region to the
      expansin-like domain. The protein also contains regions similar to mammalian
      fibronectin type III repeats, found for the first time in a fungal protein. The
      swollenin gene is regulated in a largely similar manner as the T. reesei
      cellulase genes. The biological role of SWOI was studied by disrupting the swo1
      gene from T. reesei. The disruption had no apparent effect on the growth rate on
      glucose or on different cellulosic carbon sources. Non-stringent Southern
      hybridization of Trichoderma genomic DNA with swo1 showed the presence of other
      swollenin-like genes, which could substitute for the loss of SWOI in the
      disruptant. The swollenin gene was expressed in yeast and Aspergillus niger var.
      awamori. Activity assays on cotton fibers and filter paper were performed with
      concentrated SWOI-containing yeast supernatant that disrupted the structure of
      the cotton fibers without detectable formation of reducing sugars. It also
      weakened filter paper as assayed by an extensometer. The SWOI protein was
      purified from A. niger var. awamori culture supernatant and used in an activity
      assay with Valonia cell walls. It disrupted the structure of the cell walls
      without producing detectable amounts of reducing sugars.

PMID- 12199699
TI  - Structure and function of N-acetylglucosamine kinase. Identification of two
      active site cysteines.
AB  - N-Acetylglucosamine is a major component of complex carbohydrates. The mammalian
      salvage pathway of N-acetylglucosamine recruitment from glycoconjugate
      degradation or nutritional sources starts with phosphorylation by N
      acetylglucosamine kinase. In this study we describe the identification of two
      active site cysteines of the sugar kinase by site-directed mutagenesis and
      computer-based structure prediction. Murine N-acetylglucosamine kinase contains
      six cysteine residues, all of which were mutated to serine residues. The
      strongest reduction of enzyme activity was found for the mutant C131S, followed
      by C143S. Determination of the kinetic properties of the cysteine mutants showed
      that the decreased enzyme activities were due to a strongly decreased affinity to
      either N-acetylglucosamine for C131S, or ATP for C143S. A secondary structure
      prediction of N-acetylglucosamine kinase showed a high homology to glucokinase. A
      model of the three-dimensional structure of N-acetylglucosamine kinase based on
      the known structure of glucokinase was therefore generated. This model confirmed
      that both cysteines are located in the active site of N-acetylglucosamine kinase
      with a potential role in the binding of the transferred gamma-phosphate group of
      ATP within the catalytic mechanism.

PMID- 12199700
TI  - Prediction of protein structural class by amino acid and polypeptide composition.
AB  - A new approach of predicting structural classes of protein domain sequences is
      presented in this paper. Besides the amino acid composition, the composition of
      several dipeptides, tripeptides, tetrapeptides, pentapeptides and hexapeptides
      are taken into account based on the stepwise discriminant analysis. The result of
      jackknife test shows that this new approach can lead to higher predictive
      sensitivity and specificity for reduced sequence similarity datasets. Considering
      the dataset PDB40-B constructed by Brenner and colleagues, 75.2% protein domain
      sequences are correctly assigned in the jackknife test for the four structural
      classes: all-alpha, all-beta, alpha/beta and alpha + beta, which is improved by
      19.4% in jackknife test and 25.5% in resubstitution test, in contrast with the
      component-coupled algorithm using amino acid composition alone (AAC approach) for
      the same dataset. In the cross-validation test with dataset PDB40-J constructed
      by Park and colleagues, more than 80% predictive accuracy is obtained.
      Furthermore, for the dataset constructed by Chou and Maggiona, the accuracy of
      100% and 99.7% can be easily achieved, respectively, in the resubstitution test
      and in the jackknife test merely taking the composition of dipeptides into
      account. Therefore, this new method provides an effective tool to extract
      valuable information from protein sequences, which can be used for the systematic
      analysis of small or medium size protein sequences. The computer programs used in
      this paper are available on request.

PMID- 12199701
TI  - Identification of crucial residues for the antibacterial activity of the proline
      rich peptide, pyrrhocoricin.
AB  - Members of the proline-rich antibacterial peptide family, pyrrhocoricin,
      apidaecin and drosocin appear to kill responsive bacterial species by binding to
      the multihelical lid region of the bacterial DnaK protein. Pyrrhocoricin, the
      most potent among these peptides, is nontoxic to healthy mice, and can protect
      these animals from bacterial challenge. A structure-antibacterial activity study
      of pyrrhocoricin against Escherichia coli and Agrobacterium tumefaciens
      identified the N-terminal half, residues 2-10, the region responsible for
      inhibition of the ATPase activity, as the fragment that contains the active
      segment. While fluorescein-labeled versions of the native peptides entered E.
      coli cells, deletion of the C-terminal half of pyrrhocoricin significantly
      reduced the peptide's ability to enter bacterial or mammalian cells. These
      findings highlighted pyrrhocoricin's suitability for combating intracellular
      pathogens and raised the possibility that the proline-rich antibacterial peptides
      can deliver drug leads into mammalian cells. By observing strong relationships
      between the binding to a synthetic fragment of the target protein and
      antibacterial activities of pyrrhocoricin analogs modified at strategic
      positions, we further verified that DnaK was the bacterial target macromolecule.
      Inaddition, the antimicrobial activity spectrum of native pyrrhocoricin against
      11 bacterial and fungal strains and the binding of labeled pyrrhocoricin to
      synthetic DnaK D-E helix fragments of the appropriate species could be
      correlated. Mutational analysis on a synthetic E. coli DnaK fragment identified a
      possible binding surface for pyrrhocoricin.

PMID- 12199702
TI  - A novel tachykinin-related peptide receptor. Sequence, genomic organization, and
      functional analysis.
AB  - Structurally tachykinin-related peptides have been isolated from various
      invertebrate species and shown to exhibit their biological activities through a G
      protein-coupled receptor (GPCR) for a tachykinin-related peptide. In this paper,
      we report the identification of a novel tachykinin-related peptide receptor, the
      urechistachykinin receptor (UTKR) from the echiuroid worm, Urechis unitinctus.
      The deduced UTKR precursor includes seven transmembrane domains and typical sites
      for mammalian tachykinin receptors and invertebrate tachykinin-related peptide
      receptors. A functional analysis of the UTKR expressed in Xenopus oocytes
      demonstrated that UTKR, like tachykinin receptors and tachykinin-related peptide
      receptors, activates calcium-dependent signal transduction upon binding to its
      endogenous ligands, urechistachykinins (Uru-TKs) I-V and VII, which were isolated
      as Urechis tachykinin-related peptides from the nervous tissue of the Urechis
      unitinctus in our previous study. UTKR responded to all Uru-TKs equivalently,
      showing that UTKR possesses no selective affinity with Uru-TKs. In contrast, UTKR
      was not activated by substance P or an Uru-TK analog containing a C-terminal Met
      NH2 instead of Arg-NH2. Furthermore, the genomic analysis revealed that the UTKR
      gene, like mammalian tachykinin receptor genes, consists of five exons
      interrupted by four introns, and all the intron-inserted positions are completely
      compatible with those of mammalian tachykinin receptor genes. These results
      suggest that mammalian tachykinin receptors and invertebrate tachykinin-related
      peptide receptors were evolved from a common ancestral GPCR gene. This is the
      first identification of an invertebrate tachykinin-related peptide receptor from
      other species than insects and also of the genomic structure of a tachykinin
      related peptide receptor gene.

PMID- 12199703
TI  - A synthetic weak neurotoxin binds with low affinity to Torpedo and chicken alpha7
      nicotinic acetylcholine receptors.
AB  - Weak neurotoxins from snake venom are small proteins with five disulfide bonds,
      which have been shown to be poor binders of nicotinic acetylcholine receptors. We
      report on the cloning and sequencing of four cDNAs encoding weak neurotoxins from
      Naja sputatrix venom glands. The protein encoded by one of them, Wntx-5, has been
      synthesized by solid-phase synthesis and characterized. The physicochemical
      properties of the synthetic toxin (sWntx-5) agree with those anticipated for the
      natural toxin. We show that this toxin interacts with relatively low affinity
      (K(d) = 180 nm) with the muscular-type acetylcholine receptor of the electric
      organ of T. marmorata, and with an even weaker affinity (90 microm) with the
      neuronal alpha7 receptor of chicken. Electrophysiological recordings using
      isolated mouse hemidiaphragm and frog cutaneous pectoris nerve-muscle
      preparations revealed no blocking activity of sWntx-5 at microm concentrations.
      Our data confirm previous observations that natural weak neurotoxins from cobras
      have poor affinity for nicotinic acetylcholine receptors.

PMID- 12199705
TI  - Medium-chain dehydrogenases/reductases (MDR). Family characterizations including
      genome comparisons and active site modeling.
AB  - Completed eukaryotic genomes were screened for medium-chain
      dehydrogenases/reductases (MDR). In the human genome, 23 MDR forms were found, a
      number that probably will increase, because the genome is not yet fully
      interpreted. Partial sequences already indicate that at least three further
      members exist. Within the MDR superfamily, at least eight families were
      distinguished. Three families are formed by dimeric alcohol dehydrogenases (ADH;
      originally detected in animals/plants), cinnamyl alcohol dehydrogenases
      (originally detected in plants) and tetrameric alcohol dehydrogenases (originally
      detected in yeast). Three further families are centred around forms initially
      detected as mitochondrial respiratory function proteins, acetyl-CoA reductases of
      fatty acid synthases, and leukotriene B4 dehydrogenases. The two remaining
      families with polyol dehydrogenases (originally detected as sorbitol
      dehydrogenase) and quinone reductases (originally detected as zeta-crystallin)
      are also distinct but with variable sequences. The most abundant families in the
      human genome are the dimeric ADH forms and the quinone oxidoreductases. The
      eukaryotic patterns are different from those of Escherichia coli. The different
      families were further evaluated by molecular modelling of their active sites as
      to geometry, hydrophobicity and volume of substrate-binding pockets. Finally,
      sequence patterns were derived that are diagnostic for the different families and
      can be used in genome annotations.

PMID- 12199704
TI  - Localization of N-linked carbohydrate chains in glycoprotein ZPA of the bovine
      egg zona pellucida.
AB  - The zona pellucida, a transparent envelope surrounding the mammalian oocyte,
      consists of three glycoproteins, ZPA, ZPB and ZPC, and plays a role in sperm-egg
      interactions. In bovines, these glycoproteins cannot be separated unless the
      acidic N-acetyllactosamine regions of the carbohydrate chains are removed by endo
      beta-Galactosidase digestion. Endo-beta-Galactosidase-digested ZPB retains
      stronger sperm-binding activity than ZPC. It is still unclear whether ZPA
      possesses significant activity. Recently, we reported that bovine sperm binds to
      Man5GlcNAc2, the neutral N-linked chain in the cow zona proteins. In this study,
      we investigated the localization of the sperm-ligand active high-mannose-type
      chain and the acidic complex-type chains in bovine ZPA. Three N-glycopeptides of
      ZPA, containing an N-glycosylation site at Asn83, Asn191 and Asn527,
      respectively, were obtained from endo-beta-Galactosidase-digested ZPA. Of these
      glycosylation sites, only Asn527 is present in the ZP domain common to all the
      zona proteins. The carbohydrate structures of the N-linked chains obtained from
      each N-glycopeptide were characterized by two-dimensional sugar mapping analysis,
      while considering the structures of the N-linked chains of the zona protein
      mixture reported previously. Acidic complex-type chains were found at all three N
      glycosylation sites, while Man5GlcNAc2 was found at Asn83 and Asn191, but there
      was very little of this sperm-ligand active chain at Asn527 in the ZP domain of
      ZPA.

PMID- 12199707
TI  - X-ray crystallography, CD and kinetic studies revealed the essence of the
      abnormal behaviors of the cytochrome b5 Phe35-->Tyr mutant.
AB  - Conserved phenylalanine 35 is one of the hydrophobic patch residues on the
      surface of cytochrome b5 (cyt b5). This patch is partially exposed on the surface
      of cyt b5 while its buried face is in direct van der Waals' contact with heme b.
      Residues Phe35 and Phe/Tyr74 also form an aromatic channel with His39, which is
      one of the axial ligands of heme b. By site-directed mutagenesis we have produced
      three mutants of cyt b5: Phe35-->Tyr, Phe35-->Leu, and Phe35-->His. We found that
      of these three mutants, the Phe35-->Tyr mutant displays abnormal properties. The
      redox potential of the Phe35-->Tyr mutant is 66 mV more negative than that of the
      wild-type cyt b5 and the oxidized Phe35-->Tyr mutant is more stable towards
      thermal and chemical denaturation than wild-type cyt b5. In this study we studied
      the most interesting mutant, Phe35-->Tyr, by X-ray crystallography, thermal
      denaturation, CD and kinetic studies of heme dissociation to explore the origin
      of its unusual behaviors. Analysis of crystal structure of the Phe35-->Tyr mutant
      shows that the overall structure of the mutant is basically the same as that of
      the wild-type protein. However, the introduction of a hydroxyl group in the heme
      pocket, and the increased van der Waals' and electrostatic interactions between
      the side chain of Tyr35 and the heme probably result in enhancement of stability
      of the Phe35-->Tyr mutant. The kinetic difference of the heme trapped by the heme
      pocket also supports this conclusion. The detailed conformational changes of the
      proteins in response to heat have been studied by CD for the first time,
      revealing the existence of the folding intermediate.

PMID- 12199706
TI  - Inactivation of annexin II tetramer by S-nitrosoglutathione.
AB  - We investigated the effect of nitric oxide (NO) donors on the activities of
      annexin II tetramer (AIIt), a member of the Ca2+- dependent phospholipid-binding
      protein family. Incubation of purified AIIt with S-nitrosoglutathione (GSNO) led
      to the inhibition of AIIt-mediated liposome aggregation. This effect was dose
      dependent with an IC50 of approximately 100 micro m. Sodium nitroprusside,
      another NO donor also inhibited AIIt-mediated liposome aggregation, whereas
      reduced glutathione, nitrate, or nitrite had no effects. GSNO also inhibited AIIt
      mediated membrane fusion, but not the binding of AIIt to the membrane. GSNO only
      has a modest effect on liposome aggregation mediated by annexins I, III or IV.
      The binding of AIIt to the membrane protected the reactive sites of GSNO on AIIt.
      GSNO did not inhibit AIIt-mediated liposome aggregation in the presence of
      dithiothreitol. Taken together, our results suggest that GSNO inactivates AIIt
      possibly via S-nitrosylation and/or the formation of disulfide bonds.

PMID- 12199708
TI  - Pressure and heat inactivation of recombinant human acetylcholinesterase.
      Importance of residue E202 for enzyme stability.
AB  - The effects of pressure on structure and activity of recombinant human
      acetylcholinesterase (rHuAChE) were investigated up to a pressure of 300 MPa
      using gel electrophoresis under elevated hydrostatic pressure, fluorescence of
      bound 8-anilinonaphthalene-1-sulfonate (ANS) and activity measurements following
      exposure to high pressure. Study of wild-type enzyme and three single mutants
      (D74N, E202Q, E450A) and one sextuple mutant (E84Q/E292A/D349N/E358Q/E389Q/D390N)
      showed that pressure exerts a differential action on wild-type rHuAChE and its
      mutants, allowing estimation of the contribution of carboxylic amino acid side
      chains to enzyme stability. Mutation of negatively charged residues D74 and E202
      by polar side-chains strengthened heat or pressure stability. The mutation E450A
      and the sextuple mutation caused destabilization of the enzyme to pressure.
      Thermal inactivation data on mutants showed that all of them were stabilized
      against temperature. In conclusion, pressure and thermal stability of mutants
      provided evidence that the residue E202 is a determinant of structural and
      functional stability of HuAChE.

PMID- 12199709
TI  - Identification of two cysteine residues involved in the binding of UDP-GalNAc to
      UDP-GalNAc:polypeptide N-acetylgalactosaminyltransferase 1 (GalNAc-T1).
AB  - Biosynthesis of mucin-type O-glycans is initiated by a family of UDP
      GalNAc:polypeptide N-acetylgalactosaminyltransferases, which contain several
      conserved cysteine residues among the isozymes. We found that a cysteine-specific
      reagent, p-chloromercuriphenylsulfonic acid (PCMPS), irreversibly inhibited one
      of the isozymes (GalNAc-T1). Presence of either UDP-GalNAc or UDP during PCMPS
      treatment protected GalNAc-T1 from inactivation, to the same extent. This
      suggests that GalNAc-T1 contains free cysteine residues interacting with the UDP
      moiety of the sugar donor. For the functional analysis of the cysteine residues,
      several conserved cysteine residues in GalNAc-T1 were mutated individually to
      alanine. All of the mutations except one resulted in complete inactivation or a
      drastic decrease in the activity, of the enzyme. We identified only Cys212 and
      Cys214, among the conserved cysteine residues in GalNAc-T1, as free cysteine
      residues, by cysteine-specific labeling of GalNAc-T1. To investigate the role of
      these two cysteine residues, we generated cysteine to serine mutants (C212S and
      C214S). The serine mutants were more active than the corresponding alanine
      mutants (C212A and C214A). Kinetic analysis demonstrated that the affinity of the
      serine-mutants for UDP-GalNAc was decreased, as compared to the wild type enzyme.
      The affinity for the acceptor apomucin, on the other hand, was essentially
      unaffected. The functional importance of the introduced serine residues was
      further demonstrated by the inhibition of all serine mutant enzymes with
      diisopropyl fluorophosphate. In addition, the serine mutants were more resistant
      to modification by PCMPS. Our results indicate that Cys212 and Cys214 are sites
      of PCMPS modification, and that these cysteine residues are involved in the
      interaction with the UDP moiety of UDP-GalNAc.

PMID- 12199710
TI  - Polyamines interact with DNA as molecular aggregates.
AB  - New compounds, named nuclear aggregates of polyamines, having a molecular mass of
      8000, 4800 and < 1000 Da, were found in the nuclear extracts of several
      replicating cells. Their molecular structure is based on the formation of ionic
      bonds between polyamine ammonium and phosphate groups. The production of the 4800
      Da compound, resulting from the aggregation of five or more < 1000 Da units, was
      increased in Caco-2 cells treated with the mitogen gastrin. Dissolving single
      polyamines in phosphate buffer resulted in the in vitro aggregation of polyamines
      with the formation of compounds with molecular masses identical to those of
      natural aggregates. After the interaction of the 4800 Da molecular aggregate with
      the genomic DNA at 37 degrees C, both the absorbance of DNA in phosphate buffer
      and the DNA mobility in agarose gel increased greatly. Furthermore, these
      compounds were able to protect the genomic DNA from digestion by DNase I, a
      phosphodiesterasic endonuclease. Our data indicate that the nuclear aggregate of
      polyamines interacts with DNA phosphate groups and influence, more efficaciously
      than single polyamines, both the conformation and the protection of the DNA.

PMID- 12199711
TI  - Temperature and salts effects on the peptidase activities of the recombinant
      metallooligopeptidases neurolysin and thimet oligopeptidase.
AB  - We report the recombinant neurolysin and thimet oligopeptidase (TOP) hydrolytic
      activities towards internally quenched fluorescent peptides derived from the
      peptide Abz-GGFLRRXQ-EDDnp (Abz, ortho-aminobenzoicacid; EDDnp, N-(2,4
      dinitrophenyl) ethylenediamine), in which X was substituted by 11 different
      natural amino acids. Neurolysin hydrolyzed these peptides at R-R or at R-X bonds,
      and TOP hydrolyzed at R-R or L-R bonds, showing a preference to cleave at three
      or four amino acids from the C-terminal end. The kinetic parameters of hydrolysis
      and the variations of the cleavage sites were evaluated under different
      conditions of temperature and salt concentration. The relative amount of cleavage
      varied with the nature of the substitution at the X position as well as with
      temperature and NaCl concentration. TOP was activated by all assayed salts in the
      range 0.05-0.2 m for NaCl, KCl, NH4Cl and NaI, and 0.025-0.1 m for Na2SO4.
      Concentration higher than 0.2 N NH4Cl and NaI reduced TOP activity, while 0.5 N
      or higher concentration of NaCl, KCl and Na2SO4 increased TOP activity.
      Neurolysin was strongly activated by NaCl, KCl and Na2SO4, while NH4Cl and NaI
      have very modest effect. High positive values of enthalpy (DeltaH*) and entropy
      (DeltaS*) of activation were found together with an unusual temperature
      dependence upon the hydrolysis of the substrates. The effects of low temperature
      and high NaCl concentration on the hydrolytic activities of neurolysin and TOP do
      not seem to be a consequence of large secondary structure variation of the
      proteins, as indicated by the far-UV CD spectra. However, the modulation of the
      activities of the two oligopeptidases could be related to variations of
      conformation, in limited regions of the peptidases, enough to modify their
      activities.

PMID- 12199712
TI  - The lectin from leaves of Japanese cycad, Cycas revoluta Thunb. (gymnosperm) is a
      member of the jacalin-related family.
AB  - A novel lectin was isolated from leaves of the Japanese cycad, Cycas revoluta
      Thunb. (gymnosperm), and its characteristics including amino acid composition,
      molecular mass, carbohydrate binding specificity and partial amino acid sequences
      were examined. The inhibition analysis of hemagglutinating activity with various
      sugars showed that the lectin has a carbohydrate-binding specificity similar to
      those of mannose recognizing, jacalin-related lectins. Partial amino acid
      sequences of the lysylendopeptic peptides shows that the lectin might have a
      repeating structure and belong to the jacalin-related lectin family.

PMID- 12199713
TI  - Sendai virus N-terminal fusion peptide consists of two similar repeats, both of
      which contribute to membrane fusion.
AB  - The N-terminal fusion peptide of Sendai virus F1 envelope glycoprotein is a
      stretch of 14 amino acids, most of which are hydrophobic. Following this region,
      we detected a segment of 11 residues that are strikingly similar to the N
      terminal fusion peptide. We found that, when anchored to the membrane by
      palmitoylation of its N-terminus, this segment (WT-palm-19-33) induces membrane
      fusion of large unilamellar liposomes to almost the same extent as a segment that
      includes the N-terminal fusion peptide. The activity of WT-palm-19-33 was
      dependent on its specific sequence, as a palmitoylated peptide with the same
      amino-acid composition but a scrambled sequence was inactive. Interestingly, two
      mutations (G7A and G12A) known to increase F1- induced cell-cell fusion, also
      increased the homology between the N-terminal fusion peptide and WT-palm-19-33.
      The role of the amino-acid sequence on the fusogenicity, secondary structure, and
      mechanism of membrane fusion was analyzed by comparing a peptide comprising both
      homologous segments (WT 1-33), a G12A mutant (G12A 1-33), a G7A-G12A double
      mutant (G7A-G12A 1-33), and a peptide with a scrambled sequence (SC 1-33). Based
      on these experiments, we postulate that replacement of Gly 7 and Gly12 by Ala
      increases the alpha helical content of the N-terminal region, with a concomitant
      increase in its fusogenic activity. Furthermore, the dissimilar abilities of the
      different peptides to induce membrane negative curvature as well as to promote
      isotropic 31P NMR signals, suggest that these mutations might also alter the
      extent of membrane penetration of the 33-residue peptide. Interestingly, our
      results serve to explain the effect of the G7A and G12A mutations on the
      fusogenic activity of the parent F1 protein in vivo.

PMID- 12199714
TI  - Vibrio cholerae hemolysin. Implication of amphiphilicity and lipid-induced
      conformational change for its pore-forming activity.
AB  - Vibrio cholerae hemolysin (HlyA), a water-soluble protein with a native monomeric
      relative molecular mass of 65 000, forms transmembrane pentameric channels in
      target biomembranes. The HlyA binds to lipid vesicles nonspecifically and without
      saturation; however, self-assembly is triggered specifically by cholesterol. Here
      we show that the HlyA partitioned quantitatively to amphiphilic media
      irrespective of their compositions, indicating that the toxin had an amphiphilic
      surface. Asialofetuin, a beta1-galactosyl-terminated glycoprotein, which binds
      specifically to the HlyA in a lectin-glycoprotein type of interaction and
      inhibits carbohydrate-independent interaction of the toxin with lipid, reduced
      effective amphiphilicity of the toxin significantly. Resistance of the HlyA to
      proteases together with the tryptophan fluorescence emission spectrum suggested a
      compact structure for the toxin. Fluorescence energy transfer from the HlyA to
      dansyl-phosphatidylethanolamine required the presence of cholesterol in the lipid
      bilayer and was synchronous with oligomerization. Phospholipid bilayer without
      cholesterol caused a partial unfolding of the HlyA monomer as indicated by the
      transfer of tryptophan residues from the nonpolar core of the protein to a more
      polar region. These observations suggested: (a) partitioning of the HlyA to lipid
      vesicles is driven by the tendency of the amphiphilic toxin to reduce
      energetically unfavorable contacts with water and is not affected significantly
      by the composition of the vesicles; and (b) partial unfolding of the HlyA at the
      lipid-water interface precedes and promotes cholesterol-induced oligomerization
      to an insertion-competent configuration.

PMID- 12199715
TI  - Purification and partial characterization of seven glutathione S-transferase
      isoforms from the clam Ruditapes decussatus.
AB  - This paper deals with the purification and the partial characterization of
      glutathione S-transferase (GST) isoforms from the clam Ruditapes decussatus. For
      the first step of purification, two affinity columns, reduced glutathione (GSH)
      agarose and S-hexyl GSH-agarose, were mounted in series. Four affinity fractions
      were thus recovered. Further purification was performed using anion exchange
      chromatography. Seven fractions, which present a GST activity with 1-chloro-2,4
      dinitrobenzene (CDNB) as substrate, were collected and analyzed by RP-HPLC. Seven
      distinct GST isoforms were purified, six of them were homodimers, the last one
      was a heterodimer consisting of the subunits 3 and 6. Kinetic parameters were
      studied. Results showed that isoforms have distinct affinity and Vmax for GSH and
      CDNB as substrates. The catalytic activity of the heterodimer isoform appeared to
      be a combination of the ability of each subunit. The immunological properties of
      each purified isoform were investigated using three antisera anti-pi, anti-mu and
      anti-alpha mammalian GST classes. Three isoforms (3-3, 6-6 and 3-6) seem to be
      closely related to the pi-class GST. Both isoforms 1-1 and 2-2 cross-reacted with
      antisera to pi and alpha classes and the isoform 5-5 cross-reacted with the
      antisera to mu and pi classes. Subunit 4 was recognized by the three antisera
      used, and its N-terminal amino acid analysis showed high identity (53%) with a
      conserved sequence of an alpha/m micro /pi GST from Fasciola hepatica.

PMID- 12199716
TI  - Effects of a tryptophanyl substitution on the structure and antimicrobial
      activity of C-terminally truncated gaegurin 4.
AB  - Gaegurin 4 (GGN4), a 37-residue antimicrobial peptide, consists of two
      amphipathic alpha helices (residues 2-10 and 16-32) connected by a flexible loop
      region (residues 11-15). As part of an effort to develop new peptide antibiotics
      with low molecular mass, the activities of C-terminally truncated GGN4 analogues
      were tested. Delta24-37 GGN4, a peptide analogue with 14 residues truncated from
      the C-terminus of GGN4, showed a complete loss of antimicrobial activity.
      However, the single substitution of aspartic acid 16 by tryptophan (D16W) in the
      Delta24-37 GGN4 completely restored the antimicrobial activity, without any
      significant hemolytic activity. In contrast, neither the D16F nor K15W
      substitution of the Delta24-37 GGN4 allowed such a dramatic recovery of activity.
      In addition, the D16W substitution of the native GGN4 significantly enhanced the
      hemolytic activity as well as the antimicrobial activity. The structural effect
      of the D16W substitution in the Delta24-37 GGN4 was investigated by CD, NMR, and
      fluorescence spectroscopy. The results showed that the single tryptophanyl
      substitution at position 16 of the Delta24-37 GGN4 induced an alpha helical
      conformation in the previously flexible loop region in intact GGN4, thereby
      forming an entirely amphipathic alpha helix. In addition, the substituted
      tryptophan itself plays an important role in the membrane-interaction of the
      peptide.

PMID- 12199719
TI  - Postmarketing surveillance of new antiepileptic drugs: the tribulations of
      trials.

PMID- 12199717
TI  - A zymogen form of masquerade-like serine proteinase homologue is cleaved during
      pro-phenoloxidase activation by Ca2+ in coleopteran and Tenebrio molitor larvae.
AB  - To elucidate the biochemical activation mechanism of the insect pro-phenoloxidase
      (pro-PO) system, we purified a 45-kDa protein to homogeneity from the hemolymph
      of Tenebrio molitor (mealworm) larvae, and cloned its cDNA. The overall structure
      of the 45-kDa protein is similar to Drosophila masquerade serine proteinase
      homologue, which is an essential component in Drosophila muscle development. This
      Tenebrio masquerade-like serine proteinase homologue (Tm-mas) contains a trypsin
      like serine proteinase domain in the C-terminal region, except for the
      substitution of Ser to Gly at the active site triad, and a disulfide-knotted
      domain at the amino-terminal region. When the purified 45-kDa Tm-mas was
      incubated with CM-Toyopearl eluate solution containing pro-PO and other pro-PO
      activating factors, the resulting phenoloxidase (PO) activity was shown to be
      independent of Ca2+. This suggests that the purified 45-kDa Tm-mas is an
      activated form of pro-PO activating factor. The55-kDa zymogen form of Tm-mas was
      detected in the hemolymph when PO activity was not evident. However, when
      Tenebrio hemolymph was incubated with Ca2+, a 79-kDa Tenebrio pro-PO and the 55
      kDa zymogen Tm-mas converted to 76-kDa PO and 45-kDa Tm-mas, respectively, with
      detectable PO activity. Furthermore, when Tenebrio hemolymph was incubated with
      Ca2+ and beta-1,3-glucan, the conversion of pro-PO to PO and the 55-kDa zymogen
      Tm-mas to the 45-kDa protein, was faster than in the presence of Ca2+ only. These
      results suggest that the cleavage of the 55-kDa zymogen of Tm-mas by a limited
      proteolysis is necessary for PO activity, and the Tm-mas is a pro-PO activating
      cofactor.

PMID- 12199720
TI  - Effect of gabapentin on the anticonvulsant activity of antiepileptic drugs
      against electroconvulsions in mice: an isobolographic analysis.
AB  - PURPOSE: The objective of this study was the isobolographic evaluation of the
      interactions between the novel antiepileptic drug (AED) gabapentin (GBP) and a
      number of other AEDs against electroconvulsion-induced convulsions in mice.
      METHODS: Electroconvulsions were produced by means of an alternating current (ear
      clip electrodes, 0.2-s stimulus duration, tonic hindlimb extension taken as the
      end point). Adverse effects were evaluated with the chimney test (motor
      performance) and passive-avoidance task (long-term memory). Plasma levels of AEDs
      were measured by immunofluorescence or high-pressure liquid chromatography.
      RESULTS: GBP (< or =50 mg/kg) remained ineffective on the electroconvulsive
      threshold. According to the isobolographic analysis, GBP appears to act
      synergistically with carbamazepine, valproate, phenytoin, phenobarbital (PB),
      lamotrigine (LTG), and LY 300164. The pharmacokinetic events may be responsible
      for the interactions of GBP/PB and GBP/LTG, because only PB and LTG significantly
      elevated the plasma concentration of this AED. Conversely, GBP did not affect the
      plasma levels of other AEDs used in this study. No adverse effects were induced
      by combinations of GBP with these AEDs. CONCLUSIONS: The isobolographic analysis
      revealed that combinations of GBP with other AEDs generally results in
      synergistic (supraadditive) interactions.

PMID- 12199721
TI  - Effect of electrical stimulation of the nucleus of the solitary tract on the
      development of electrical amygdaloid kindling in the cat.
AB  - PURPOSE: This work analyzed the effect of electrical stimulation of the nucleus
      of the solitary tract (NTS) on the development of electrical amygdaloid kindling
      (AK) in freely moving cats. METHODS: Nine male adult cats with implanted
      electrodes in both amygdalae (basolateral nucleus), both lateral geniculate
      bodies, left NTS, and both prefrontal cortices were used. Electromyogram and
      electrooculogram also were recorded. The AK was performed every 24 h (1-s train,
      1-ms pulses, 60 Hz, 300-600 microA). The NTS was stimulated previously for 1 min
      (0.5-ms pulses, 30 Hz, 150-300 microA), just before the AK at 10:00 a.m., and
      then every 60 min, 4 times, from 11:00 a.m. to 2:00 p.m. On different days, all
      NTS stimulation was suspended, and AK was continued until stage VI kindling was
      reached. RESULTS: Behavioral changes produced by the stimulation of the NTS were
      blinking, immobility periods with upward sight, licking, and swallowing. Animals
      with simultaneous stimulation of NTS and AK did not reach stage VI, remaining in
      behavioral stages I-III. Stage VI was reached after NTS stimulation was
      intentionally suspended. The amplitude, duration, and the propagation of the
      amygdaloid afterdischarge did not exhibit progressive evolution during NTS
      stimulation. A regression analysis was performed between the number of days with
      only AK stimulation and days with simultaneous NTS stimulation, which showed a
      positive correlation (values of r = 0.84). CONCLUSIONS: Our results suggest that
      NTS stimulation interferes with the development of convulsive evolution and
      secondary generalization. This delay effect may be due to the activation of the
      locus ceruleus and some areas of the midbrain reticular formation, among other
      structures, which has been demonstrated to inhibit experimental convulsive
      seizures.

PMID- 12199722
TI  - Increased excitability and decreased sensitivity to GABA in an animal model of
      dysplastic cortex.
AB  - PURPOSE: Cortical dysplasia (CD) is associated with epilepsy in both the
      pediatric and adult populations. The mechanism underlying seizures with cortical
      malformations is still poorly understood. To study the physiology of dysplastic
      cortex, we developed an experimental model of CD. METHODS: Pregnant rats were
      given intraperitoneal injections of carmustine (1-3-bis-chloroethyl-nitrosourea;
      BCNU) on embryonic day 15 (E15). Cortical histology was examined in the resulting
      pups at P0, P28, and P60. In addition, evoked and spontaneous field potential
      recordings were obtained in cortical slices from adult control and BCNU-exposed
      rats. Finally, we used whole-cell recordings to compare physiologic properties of
      pyramidal neurons and gamma-aminobutyric acid (GABA) responses in control and
      BCNU-treated animals. RESULTS: Features characteristic of CD were found in the
      offspring, including laminar disorganization, cytomegalic neurons, and neuronal
      heterotopias. Dysplastic cortex also contained abnormal clusters of Cajal-Retzius
      (CR) cells and disruption of radial glial fibers, as demonstrated with
      immunohistochemistry. Under conditions of partial GABAA-receptor blockade with 10
      microM bicuculline methiodide (BMI), slices of dysplastic cortex demonstrated a
      significant increase in the number of spontaneous and evoked epileptiform
      discharges. Individual pyramidal neurons in dysplastic cortex were less sensitive
      to application of GABA compared with controls. CONCLUSIONS: BCNU exposure in
      utero produces histologic alterations suggestive of CD in rat offspring.
      Dysplastic cortex from this model demonstrates features of hyperexcitability and
      decreased neuronal sensitivity to GABA. Such physiologic alterations may underlie
      the increased epileptogenicity of dysplastic cortex.

PMID- 12199724
TI  - Gabapentin versus lamotrigine monotherapy: a double-blind comparison in newly
      diagnosed epilepsy.
AB  - PURPOSE: This randomised, double-blind study compared the newer antiepileptic
      drugs (AEDs) gabapentin (GBP) and lamotrigine (LTG) as monotherapy in newly
      diagnosed epilepsy. METHODS: Patients with partial seizures with and/or without
      secondary generalization or primary generalized tonic-clonic seizures were
      randomized to either GBP or LTG. During 2- and 6-week titration periods,
      respectively, GBP dosage reached 1,800 mg/day, and LTG, 150 mg/day. In the
      subsequent 24-week maintenance phase, the dose could be adjusted based on seizure
      control or adverse events between 1,200 and 3,600 mg/day for GBP and 100 and 300
      mg/day for LTG. The primary end point was time to exit, a composite of efficacy
      and tolerability. Evaluable patients were used for the primary efficacy analysis,
      whereas tolerability was examined on an intent-to-treat basis. RESULTS: A total
      of 309 patients was randomized, and 291 (148 GBP, 143 LTG) were included in the
      evaluable population. Nineteen patients in each group had an exit event. The
      median time to exit was 69 days for GBP and 48 days for LTG. The hazard ratio was
      estimated as 1.043 (90% confidence intervals, 0.602-1.809). Overall, 106 (71.6%
      of the evaluable population) GBP-treated and 96 (67.1%) LTG-treated patients
      completed the study. Of those, 80 (75.5%) patients taking GBP and 73 (76.0%)
      taking LTG remained seizure free during the final 12 weeks of treatment. Only 14
      (8.9%) GBP-treated patients and 15 (9.9%) LTG-treated patients withdrew because
      of study drug-related adverse events. CONCLUSIONS: GBP and LTG monotherapy were
      similarly effective and well tolerated in patients with newly diagnosed epilepsy.

PMID- 12199723
TI  - A postmarketing surveillance study of gabapentin as add-on therapy for 3,100
      patients in England.
AB  - PURPOSE: Our aim was to monitor the use of gabapentin (GBP) by patients
      prescribed this drug by primary care physicians in England soon after it was
      marketed in the United Kingdom. METHODS: A noninterventional observational cohort
      study was conducted by using the technique of prescription-event monitoring.
      Patients were identified from dispensed National Health Service prescriptions.
      Outcome data were obtained from questionnaires sent to the doctor approximately 6
      months after the initial prescription. These data included demographic
      information, events reported since starting GBP, and reason for stopping the
      drug, if it was stopped. Incidence rates were calculated for given periods for
      all events reported. Additional information was requested for selected events of
      medical interest, including pregnancies. Standardised mortality ratio (SMR) was
      calculated. RESULTS: The cohort comprised 3,100 patients, of whom 136 (4%) were
      children. The median duration of treatment was 8.1 months. The most frequently
      reported adverse events reported during the first month of treatment,
      drowsiness/sedation, dizziness, and malaise/lassitude, also were the commonest
      reasons for discontinuing GBP and reported as suspected adverse drug reactions
      (ADRs). There were no congenital anomalies in the 11 babies born to women who
      used GBP during the first trimester of pregnancy. Crude mortality rate was 5
      times that in general population but similar to that in other published studies.
      CONCLUSIONS: Neurologic-related events were the most frequently reported adverse
      events. They also were the commonest reasons for discontinuing treatment and
      reported as suspected ADRs. No previously unrecognised adverse events were
      detected in this large cohort of patients who were among the first treated with
      gabapentin in England.

PMID- 12199725
TI  - Neural networks underlying epileptic humming.
AB  - PURPOSE: Humming is a rare automatism occurring in partial seizures that has
      received little attention. Its study could shed light on the neural networks
      underlying melodic expression. In this study, we examined the
      anatomoelectroclinical correlates of humming during epileptic seizures METHODS:
      Three patients undergoing presurgical stereoelectroencephalography (SEEG) for
      medically intractable temporal lobe epilepsy were studied. Coherence analysis of
      SEEG activity was carried out to study the functional coupling of different
      regions of the brain, whereas time-frequency (TF) analysis was conducted to
      assess epileptic discharge patterns. Changes in coherence were studied to
      identify the neural structures/systems implicated in humming. RESULTS: Humming
      began after the onset of seizures generated in medial limbic regions of the
      temporal lobe. At seizure onset, coherence analysis showed an increase in
      amygdala-hippocampus coupling. Humming began after the onset of a rhythmic
      discharge over lateral regions of the superior temporal gyrus (STG). A highly
      significant increase in coherence was observed between prefrontal regions and the
      STG. TF analysis of the STG discharge showed a reproducible pattern with a single
      fundamental frequency and associated harmonics. This frequency was approximately
      6 Hz for two patients and 15 Hz for one patient. CONCLUSIONS: These findings
      suggest that the occurrence of humming during epileptic seizures of the temporal
      lobe is associated with activity in a neural network involving the STG and the
      inferior frontal gyrus.

PMID- 12199726
TI  - Interictal EEG abnormalities in patients with psychogenic nonepileptic seizures.
AB  - PURPOSE: To examine interictal EEG abnormalities in patients with psychogenic
      nonepileptic seizures (PNESs). METHODS: (a) Retrospective study of EEG reports of
      187 consecutive patients with PNES seen at the Department of Epileptology, Bonn,
      Germany; (b) Blinded, multirater comparison of EEGs of all PNES patients with no
      other clinically recognizable cause of EEG disturbance (n = 50) and healthy
      controls (n = 50). RESULTS: Of 187 consecutive patients with PNESs, 57 patients
      had PNESs and epilepsy (PNES+E), and 130 patients, PNESs alone. The diagnosis of
      additional epilepsy was based on ictal (video-) EEG or on the critical assessment
      of all clinical data by an experienced epileptologist. Retrospective review of
      all available EEG reports showed that 92.9% of patients in the PNES+E and 53.8%
      in the PNES-only group had one or more abnormal EEGs (median number of EEGs per
      patient, three; range, one to 42). In the PNES-only group, EEG changes were
      nonspecific in 42.3% of patients. Only 50 of 130 patients with PNESs alone had no
      other clinically recognizable cause of EEG disturbance and entered the controlled
      study. In this study, 18% of patients and 10% of controls had abnormal EEGs. The
      frequency of epileptiform EEG changes was similar to that in previous population
      studies in both groups (2.0%). CONCLUSIONS: PNESs often occur in patients with
      organic brain disease. Even in patients with PNESs alone and no clinically
      recognizable cause of EEG disturbance, nonspecific abnormalities are found 1.8
      times as often as in healthy controls. Interictal EEG changes are common in
      patients with PNESs and, in isolation, should not be interpreted as evidence of
      epilepsy.

PMID- 12199728
TI  - FDG-PET images quantified by probabilistic atlas of brain and surgical prognosis
      of temporal lobe epilepsy.
AB  - PURPOSE: This study evaluated the relation between hypometabolism, diagnosed by
      fluorodeoxyglucose positron emission tomography (FDG-PET), and the surgical
      outcome of a large and homogeneous series of cases of mesial temporal lobe
      epilepsy (mTLE), by using a probabilistic atlas of the human brain (statistical
      probabilistic anatomical maps: SPAM). METHODS: Ninety-five surgically proven
      intractable mTLE patients and 22 age-matched controls were spatially normalized
      to the average brain PET template of international consortium of brain mapping
      (ICBM). The diagnosis of mTLE was confirmed by the presence of hippocampal
      sclerosis on magnetic resonance imaging (MRI) and video-EEG monitoring. Counts
      from normalized PET images were multiplied by the probability from 98 volumes of
      interest (VOIs) of SPAM. Asymmetric indexes (AIs) reflecting the severity of
      hypometabolism were calculated by counts of selected 12 VOIs from SPAM images in
      both temporal lobes. Extent of hypometabolism was determined by the number of
      voxels showing decreased metabolism in each VOI segmented by SPAM. RESULTS: Of
      the 95 patients studied, 76 (80%) were seizure free, and 19 (20%) had
      postoperative seizures for the > or =2-year follow-up period. No significant
      association between the severity of hypometabolism in each VOI of the temporal
      lobe and surgical outcome was identified (p > 0.05). The number of voxels showing
      decreased hypometabolism was not significantly different between the good- and
      poor-outcome groups (p > 0.05). CONCLUSIONS: Our results demonstrated that focal
      severity and extent of hypometabolism quantified by a probabilistic atlas of
      brain were not related to the surgical outcome in mTLE patients who had
      hippocampal sclerosis on MRI. We should develop a more localized and specified
      anatomic map for mTLE for further results.

PMID- 12199727
TI  - A short-echo-time proton magnetic resonance spectroscopic imaging study of
      temporal lobe epilepsy.
AB  - PURPOSE: We used short-echo-time proton magnetic resonance spectroscopy imaging
      (MRSI) to study metabolite concentration variation through the temporal lobe in
      patients with temporal lobe epilepsy (TLE) with and without abnormal MRI.
      METHODS: MRSI was performed at TE = 30 ms to study 10 control subjects, 10
      patients with TLE and unilateral hippocampal sclerosis, and 10 patients with TLE
      and unremarkable MRI (MRI negative). We measured the concentrations of N-acetyl
      aspartate +N-acetyl aspartyl-glutamate (NAAt), creatine (Cr), choline (Cho),
      glutamate + glutamine (Glx), and myoinositol, in the anterior, middle, and
      posterior medial temporal lobe (MTL), and in the posterior lateral temporal lobe.
      Segmented volumetric T1-weighted MRIs gave the tissue composition of each MRSI
      voxel. Normal ranges were defined as the control mean +/- 3 SD. RESULTS: In the
      hippocampal sclerosis group, seven of 10 had abnormally low NAAt in the
      ipsilateral anterior MTL. In the MRI-negative group, four of 10 had low NAAt in
      the middle MTL voxel ipsilateral to seizure onset. Metabolite ratios were less
      sensitive to abnormality than was the NAAt concentration. Group analysis showed
      low NAAt, Cr, and Cho in the anterior MTL in hippocampal sclerosis. Glx was
      elevated in the anterior voxel contralateral to seizure onset in the MRI-negative
      group. Metabolite concentrations were influenced by voxel position and tissue
      composition. CONCLUSIONS: (a) Low NAAt, Cr, and Cho were features of the anterior
      sclerotic hippocampus, whereas low NAAt was observed in the MRI-negative group in
      the middle MTL region. The posterior temporal lobe regions were not associated
      with significant metabolite abnormality; (b) The two patient groups demonstrated
      different metabolite profiles across the temporal lobe, with elevated Glx a
      feature of the MRI-negative group; and (c) Voxel tissue composition and position
      influenced obtained metabolite concentrations.

PMID- 12199729
TI  - Quantitative analysis of benzodiazepine receptor in temporal lobe epilepsy:
      [(125)I]iomazenil autoradiographic study of surgically resected specimens.
AB  - PURPOSE: To evaluate the changes of the inhibitory neurotransmitter receptor
      system related to epileptogenesis by measuring central benzodiazepine receptors
      (BZDRs) in surgically resected specimens of temporal lobe epilepsy by using
      [(125)I]iomazenil autoradiography. METHODS: Surgically resected specimens were
      obtained from 66 temporal lobe epilepsy patients [51 with mesial temporal lobe
      epilepsy (MTLE) and 15 with non-MTLE] receiving no BZDs and seven MTLE patients
      receiving BZDs. BZDR densities in brain sections were measured by using
      [(125)I]iomazenil autoradiography. Cell densities were measured from cresyl
      violet-stained sections. RESULTS: Compared with non-MTLE patients, non-BZD
      treated MTLE patients showed remarkable reduction of BZDR density in the
      pyramidal cell region of cornu ammonis (CA) 1, CA3, and CA4, and a smaller but
      significant reduction in CA2 and the molecular and granule cell layers of dentate
      gyrus (mDG). In the MTLE group, the BZDR density in the mDG correlated with that
      in lateral cortex. Significant correlations between BZDR density and cell density
      were found in all hippocampal regions. A significant difference in BZDR
      density/cell-density ratio was observed in CA1 region between MTLE and non-MTLE.
      BZD-treated patients tended to have lower BZDR densities than did non-BZD-treated
      patients, although the differences did not reach significance. In all MTLE cases,
      [(123)I]iomazenil singlephoton emission computed tomography (SPECT) showed
      decreased BZDR binding in MTL. CONCLUSIONS: In MTLE, BZDR densities decreased
      parallel to reduction in cell density in most hippocampal subfields, but BZDR
      density appeared to decrease in excess of neuron loss in CA1. [(125)I]iomazenil
      SPECT might be useful for detecting in vivo changes of BZDR density.

PMID- 12199730
TI  - Prediction of seizure-onset laterality by using Wada memory asymmetries in
      pediatric epilepsy surgery candidates.
AB  - PURPOSE: Because the capacity of intracarotid amobarbital (Wada) memory
      assessment to predict seizure-onset laterality in children has not been
      thoroughly investigated, three comprehensive epilepsy surgery centers pooled
      their data and examined Wada memory asymmetries to predict side of seizure onset
      in children being considered for epilepsy surgery. METHODS: One hundred fifty-two
      children with intractable epilepsy underwent Wada testing. Although the type and
      number of memory stimuli and methods varied at each institution, all children
      were presented with six to 10 items soon after amobarbital injection. After
      return to neurologic baseline, recognition memory for the stimuli was assessed.
      Seizure onset was determined by simultaneous video-EEG recordings of multiple
      seizures. RESULTS: In children with unilateral temporal lobe seizures (n = 87),
      Wada memory asymmetries accurately predicted seizure laterality to a
      statistically significant degree. Wada memory asymmetries also correctly
      predicted side of seizure onset in children with extra-temporal lobe seizures (n
      = 65). Although individual patient prediction accuracy was statistically
      significant in temporal lobe cases, onset laterality was incorrectly predicted in
      < or =52% of children with left temporal lobe seizure onset, depending on the
      methods and asymmetry criterion used. There also were significant differences
      between Wada prediction accuracy across the three epilepsy centers. CONCLUSIONS:
      Results suggest that Wada memory assessment is useful in predicting side of
      seizure onset in many children. However, Wada memory asymmetries should be
      interpreted more cautiously in children than in adults.

PMID- 12199731
TI  - Sodium methohexital (brevital) as an anesthetic in the Wada test.
AB  - PURPOSES: We report our experience with sodium methohexital (Brevital) as an
      anesthetic used in the Wada test for language and memory in 86 epilepsy surgery
      patients (173 procedures). METHODS: The methods are compared with those of the
      more commonly used anesthetic sodium amobarbital (Amytal). RESULTS: Despite
      differences between the methohexital and amobarbital test protocols, the
      behavioral and neurologic effects of the two anesthetics are similar. Because of
      the brief duration of methohexital, two successive injections are made on each
      side rather than one, to lengthen the time available for testing both language
      and memory. Behavioral and EEG indices return to baseline more quickly and more
      completely with methohexital than with amobarbital, allowing several repetitions
      of the procedure without incremental drowsiness, and the total time taken for the
      procedure is less with methohexital than with amobarbital. CONCLUSIONS: The
      results of language and memory testing in the Wada test are equivalent for
      amobarbital and methohexital, except that methohexital has a briefer duration of
      action and is associated with less sedation.

PMID- 12199732
TI  - The neurodevelopmental impact of childhood-onset temporal lobe epilepsy on brain
      structure and function.
AB  - PURPOSE: To characterize the neurodevelopmental correlates of childhood-onset
      temporal lobe epilepsy on brain structure and cognition compared with late-onset
      chronic temporal lobe epilepsy and healthy controls. METHODS: Healthy controls (n
      = 62) and patients with early (n = 37) versus late (n = 16) age at onset of
      temporal lobe epilepsy were compared with high-resolution quantitative magnetic
      resonance imaging (MRI) volumetrics and comprehensive neuropsychological
      assessment. RESULTS: Patients with childhood-onset temporal lobe epilepsy (mean
      onset age, 7.8 years) exhibited widespread compromise in neuropsychological
      performance and substantial reduction in brain tissue volumes extending to
      extratemporal regions compared with healthy controls and late-onset temporal lobe
      epilepsy patients (mean onset age, 23.3 years). Most evident was reduced total
      white-matter volume among the childhood-onset patients. Reduction in brain tissue
      volume, especially total white-matter volume, was associated with significantly
      poorer cognitive status, attesting to the clinical significance of the volumetric
      abnormalities. CONCLUSIONS: Childhood-onset temporal lobe epilepsy appears to be
      associated with an adverse neurodevelopmental impact on brain structure and
      cognition that appears generalized in nature and especially evident in white
      matter tissue volume.

PMID- 12199733
TI  - Concomitant treatment with topiramate and ketogenic diet in pediatric epilepsy.
AB  - PURPOSE: Topiramate (TPM) is widely used as add-on therapy for epilepsy. TPM
      inhibits carbonic anhydrase, which may result in metabolic acidosis from
      decreased serum bicarbonate. The ketogenic diet (KGD) predisposes patients to
      metabolic acidosis, especially during induction. In children with refractory
      epilepsy, cotreatment with TPM and KGD may be considered, but special attention
      should be paid to the combined risks for metabolic acidosis and nephrolithiasis.
      We report our experience in 14 children cotreated with TPM and the KGD. METHODS:
      Medical records of 14 children cotreated with the KGD and TPM for medically
      refractory epilepsy were reviewed retrospectively. Bicarbonate levels were
      analyzed and correlated with clinical profiles, including duration of
      cotreatment, TPM dose, KGD ratio, and seizure control. RESULTS: Nine children had
      a <20% decrease in bicarbonate levels, from 5.3 to 12.3 mEq/L (mean, 7.6 mEq/L).
      Cotreatment was continued in all patients for duration of 33 to 544 days (seven
      had remained on cotreatment at the end of the study period), although two
      children required bicarbonate supplements to continue the KGD. No patient had
      nephrolithiasis. CONCLUSIONS: Although a large decrease in bicarbonate level
      occurred in the majority of children, the decrease appeared mostly at the time of
      KGD induction when added to prior TPM therapy. Bicarbonate levels should be
      monitored carefully with TPM and KGD cotreatment, and bicarbonate supplements
      given when symptomatic.

PMID- 12199734
TI  - Morbidity and accidents in patients with epilepsy: results of a European cohort
      study.
AB  - PURPOSE: To assess the risk of illnesses and accidents in patients with epilepsy
      and to evaluate the proportion of those risks attributable to epilepsy. METHODS:
      Nine hundred fifty-one referral patients with idiopathic, cryptogenic, or remote
      symptomatic epilepsy and 909 matched controls (relatives or friends) were
      followed up prospectively for 1-2 years in eight European countries (Italy,
      Germany, Holland, England, Portugal, Russia, Estonia, and Slovenia). Each patient
      and control received a diary to keep notes regarding any illness or accident.
      Patients with epilepsy specifically recorded relations with seizures. RESULTS:
      Six hundred forty-four patients recorded 2,491 illnesses compared with 1,665
      illnesses in 508 controls. The cumulative probability of illness in patients was
      49% by 12 months and 86% by 24 months (controls, 39 and 75%; p < 0.0001). One
      hundred ninety-nine patients and 124 controls had 270 and 140 accidents,
      respectively. The cumulative probability of accident in the cases was 17 and 27%
      by 12 and 24 months (controls, 12 and 17%; p < 0.0001). The chance of two or more
      illnesses or accidents was modestly but significantly greater in the patients.
      Illnesses and accidents were mostly trivial. Thirty percent of illnesses and 24%
      of accidents were seizure related. When illnesses and accidents related to
      seizures were excluded, the chance of illnesses and accidents was fairly similar
      in the two groups. CONCLUSIONS: Patients with idiopathic, cryptogenic, or remote
      symptomatic epilepsy have a moderately higher risk of illnesses and accidents
      than do the general population. With few exceptions, the events are trivial. When
      seizure-related events are excluded, patients with epilepsy are not at any
      significantly higher risk of illnesses and accidents.

PMID- 12199735
TI  - Principles of health-related quality of life: assessment in clinical trials.

PMID- 12199737
TI  - Valproate-induced encephalopathy: assessment with MR imaging and 1H MR
      spectroscopy.
AB  - The anticonvulsant agent valproate (VPA) may cause hyperammonemic encephalopathy.
      Magnetic resonance imaging (MRI) and proton MR spectroscopic (MRS) findings in a
      patient with VPA-induced hyperammonemic encephalopathy are described. MRI showed
      a metabolic-toxic lesion pattern with bilateral T2-hyperintense lesions in the
      cerebellar white matter and in the globus pallidus. MR spectroscopic findings
      were indistinguishable from hepatic encephalopathy with severe depletion of
      myoinositol and choline and with glutamine excess. N-Acetylaspartate levels were
      moderately decreased. Quantitative MRS gave detailed insight into alterations of
      brain metabolism in VPA-induced encephalopathy.

PMID- 12199736
TI  - Mild generalized epilepsy and developmental disorder associated with large inv
      dup(15).
AB  - PURPOSE: Several studies attempted to clarify the genotype-phenotype correlations
      in patients with inverted duplication of chromosome 15 [inv dup(15)], which is
      usually characterized by severe mental retardation and epilepsy in individuals
      with large duplications including the Prader-Willi/Angelman region. We report two
      patients with inv dup(15) who, in spite of a large duplication, had a mild
      phenotype including adult-onset epilepsy. This report may help to define the
      milder spectrum of the syndrome. METHODS: A 25-year-old girl with mild mental
      retardation had a 6-year history of absence seizures, with occasional head drop.
      Interictal EEG revealed diffuse spike-wave complexes. Epilepsy was well
      controlled by a combination of lamotrigine (LTG) and valproate (VPA). The other
      patient, a 27-year-old man with mild mental retardation, had a 5-year history of
      rare generalized tonic-clonic seizure during sleep, and frequent episodes of
      unresponsiveness, which appeared to be atypical absence seizures on video-EEG
      recordings. A combination of VPA and LTG led to a remarkable improvement,
      although no complete control. RESULTS: Molecular analysis revealed a large inv
      dup15 in both patients. CONCLUSIONS: The discrepancy between the mild phenotype
      and the severe chromosomal abnormality detected in these two patients further
      supports the notion that the site of breakpoint might be contributory to the inv
      dup(15) phenotype. Inv dup(15) should be considered in atypical cases of
      generalized epilepsy of adult onset without clear-cut etiology.

PMID- 12199738
TI  - Epileptic negative myoclonus in a newborn with hemimegalencephaly.
AB  - PURPOSE: We report the case of a male newborn with Ohtahara syndrome and right
      hemimegalencephaly who presented epileptic negative myoclonus in the first days
      of life. METHODS: Prolonged polygraphic studies were performed, as well as MRI
      and a full clinical examination. RESULTS: EEG showed a constant and nonreactive
      pattern of burst suppression. There were several kinds of electro-clinical
      seizures (generalized myoclonia, short atonias, typical spasm and tonic spasms)
      at the beginning of the EEG's burst. The periods of EMG silence, lasting less
      than 300 ms, were associated with stereotyped EEG transients. CONCLUSIONS:
      Epileptic negative myoclonus can be observed also in neonatal age. The short
      transient impairment of motor function observed in the newborn seems linked to
      the slow component of spike-wave discharge, but its mechanism is still not clear.

PMID- 12199751
TI  - Lobular carcinoma in situ and invasive cancer: the management controversy.

PMID- 12199752
TI  - Lobular carcinoma in situ and invasive cancer: the contralateral breast
      controversy.
AB  - We determined if the risk of relapse is increased in patients with the
      concomitant diagnosis of lobular carcinoma in situ (LCIS) and an invasive cancer,
      suggesting the need for a more aggressive surgical approach. A retrospective
      chart review was conducted from the University of Michigan's Cancer Registry of
      patients with LCIS and a simultaneous invasive cancer and patients with invasive
      cancer only diagnosed between 1981 and 1997. The two groups were compared
      statistically with the following variables: age at diagnosis, tumor stage,
      histopathologic type of cancer, type of surgery, first line of treatment, relapse
      status with dates, site of relapse, and vital status. Statistically significant
      differences were found in the distribution of age (mean p = 0.0484 and median p =
      0.0216), and histopathologic type of cancer (p < 0.0001). No significant
      difference was noted in the overall survival between the two groups (p = 0.511).
      There was also a significant difference in the relapse-free survival curves
      between the groups (p = 0.032). The risk of relapse was almost double (1.92) for
      the cancer-only patients relative to patients with LCIS as a histologic component
      of cancer. There was no significant increase in contralateral or ipsilateral
      breast recurrence for patients with LCIS and an invasive cancer compared to an
      invasive cancer alone. This lends support to the use of breast conservation
      therapy for invasive cancer patients with a histologic component of LCIS. The
      significant difference in the types of cancer may support the theory of genetic
      progression of LCIS to cancer, but clearly further data are required to prove
      this hypothesis.

PMID- 12199753
TI  - Large-needle core biopsy in atypical intraductal epithelial hyperplasia including
      immunohistochemical expression of high molecular weight cytokeratin: analysis of
      results of a single institution.
AB  - The diagnosis of atypical intraductal epithelial hyperplasia (AIDH) constitutes
      6.3% of the breast core biopsies performed at our institution. Seventy-nine cases
      that were diagnosed as AIDH on core biopsy and went through excisional biopsy
      were included. Sixty-four biopsies were performed by an image-guided 11-gauge
      vacuum device, 11 under sonographic guidance using 14-gauge needles and 4 by a
      sonographically guided 11-gauge vacuum device. The histopathology of the core
      biopsies and the surgical excisions were reviewed. Immunohistochemistry was
      performed on the consecutive sections of core biopsy specimens using high
      molecular weight cytokeratin (HMW-CK) (DAKO-Cytokeratin, 34betaE12). At
      interpretation of the stain, intensity and percentage of positive cells were
      taken into account. The immunoprofiles of AIDH were categorized into four groups
      showing negative (i.e., no staining) or low-, moderate-, high-, and very high
      intensity staining. Surgical excision of the 79 lesions revealed carcinoma in
      only 3 cases (4%)-two infiltrating carcinomas and one intraductal carcinoma
      residual AIDH in 44 cases (56%), and epithelial hyperplasia or other benign
      lesions without atypia in 32 cases (40%). The HMW-CK stain was performed
      retrospectively on all of the core biopsies and 66 of them contained residual
      areas with AIDH for staining. Forty-nine (74%) were CK negative or stained with
      low intensity, but 17 cases (26%) had a moderate- to high-intensity stain. Our
      study showed a lower incidence of carcinoma on surgical excision following core
      biopsy for AIDH than other studies. The HMW-CK stain helped to characterize the
      nature of the intraductal proliferation and to confirm the presence of atypia, as
      has been previously reported, but frequently was inconclusive. The low incidence
      of carcinoma brings into question the need for surgical excision of all cases of
      AIDH diagnosed by core biopsy.

PMID- 12199754
TI  - Three years of experience with advanced breast biopsy instrumentation (ABBI).
AB  - This article reports our experience using the advanced breast biopsy instrument
      (ABBI) system for excisional biopsy of mammographically visible nonpalpable
      breast lesions. Patients with nonpalpable mammographically detected breast
      lesions were evaluated as potential ABBI candidates. Selection criteria included
      noncystic lesions for which complete removal or large sampling was indicated,
      compressed thickness of the breast of more than 25 mm, and the patient's ability
      to lie prone for at least 1 hour. During the period August 1997-April 2000 (33
      months), 284 patients were found to be potential ABBI candidates. Sixteen
      patients were subsequently excluded. Biopsies using the ABBI system were
      performed in 268 cases, yielding an overall technical success rate of 94.4%. The
      mammographic abnormalities included mass in 125 cases (46.6%), mass with
      calcifications in 63 cases (23.5%), and microcalcifications without a mass in 80
      cases (29.8%). Histologically 56 specimens (20.9%) were malignant (mass in 30
      cases, mass with calcifications in 12, and microcalcifications in 14) and 212
      (79.1%) were benign. Carcinoma in situ was found in 17 cases (30.4%), invasive
      carcinoma in 35 cases (62.5%), tubular carcinoma in 2 cases (3.6%), metastatic
      intramammary lymph node of previously unknown malignant melanoma in 1 case, and
      malignant lymphoma in 1 case. Open reexcision was performed in 54 cases with
      primary breast cancer. The histologic investigation revealed that in 26 (48.15%)
      cases the mammographic lesion was completely excised and in 28 (51.85%) cases the
      margins involved malignant residue and/or other foci of carcinoma. There were
      complications in 17 cases: wound infection in 2, ecchymosis in 9, seroma in 5,
      and a large immediate hematoma in 1 patient. Only the latter patient required
      immediate revision and drainage; the remainder underwent successful conservative
      treatment. Most nonpalpable breast lesions, if selected properly, are accessible
      for ABBI procedure. The biopsy causes minimal complications and minimal
      distortion of the breast architecture. Should relumpectomy be needed after the
      ABBI procedure, the tunnel of the cannula path is easily recognized, leaving no
      need for needle localization.

PMID- 12199755
TI  - Relationship between serum prolactin levels and histology of benign and malignant
      breast lesions: a detailed study of 153 consecutive cases.
AB  - This study was aimed at investigating the relationship between serum prolactin
      levels and the morphology of operable female breast lesions. One hundred fifty
      three consecutive patients with operable benign and malignant breast lesions in
      whom preoperative serum prolactin levels had been determined were stratified into
      five groups according to their serum prolactin levels. The histologic findings in
      these groups were analyzed and compared. Most patients (93%) had serum prolactin
      levels within the normal limits. Of the 54 patients with benign lesions, only
      4(7%) had slightly elevated serum prolactin levels. Two of these patients had
      fibroadenomas, one had a phyllodes tumor and one had fibrocystic change. Of the
      99 patients with carcinoma, 7 (7%) had hyperprolactinemia. Five of the seven
      tumors were invasive and two were in situ. All seven tumors were of low or
      intermediate grade of malignancy. The two cases with the highest prolactin levels
      (3057 and 1822 mU/L) were both intermediate-grade ductal carcinoma in situ
      (DCIS). It is concluded that the great majority of patients presenting with
      operable breast lesions have normal serum prolactin levels, and that elevated
      levels, when present, occur with equal frequency in patients with benign and
      malignant breast lesions. Hyperprolactinemic patients presenting with carcinoma
      in this study, none of whom had a history of recent pregnancy or lactation,
      tended to have histologically low- or intermediate-grade tumors, but this needs
      to be confirmed by investigating more cases.

PMID- 12199756
TI  - Ectopic breast cancer: special treatment considerations in the postmenopausal
      patient.
AB  - A 70-year-old woman with congenital bilateral accessory nipples developed a
      clinical mass and pain in the left accessory breast tissue. Excision revealed a
      T2 invasive ductal carcinoma with an identifiable in situ component. No masses
      were present in the normal breast, and 9 years after surgery, radiation therapy,
      and tamoxifen there has been no recurrence either in the ipsilateral affected
      accessory or normal breast tissue.

PMID- 12199757
TI  - Nodular myofibroblastic stromal hyperplasia of the mammary gland as an accurate
      name for pseudoangiomatous stromal hyperplasia of the mammary gland.
AB  - Pseudoangiomatous stromal hyperplasia (PASH) of the mammary gland is a well-known
      benign localized form of stromal overgrowth with probable hormonal etiology. We
      describe the histologic findings and immunohistochemistry of two cases. Two
      women, 16 and 58 years old, presented with a breast mass and underwent surgical
      excision. Grossly, they consisted of a well-circumscribed, rubbery tissue with a
      solid white-tan homogeneous cut surface. One of the cases showed focal cystic
      areas. Histologically the lesion showed a proliferation of the collagenous stroma
      with varying degrees of density, and hyalinization with many pseudovascular slit
      like anastomosing spaces lined by spindle cells with scant cytoplasm and bland
      chromatin. The spindle cells lining the spaces were strongly reactive for
      vimentin and weakly reactive for CD34, actin, and desmin. They were negative for
      factor VIII, S-100, and pankeratin. In PASH, the "pseudoangiomatous" term
      describes a recognizable pattern but does not describe the tumor's histologic
      nature. We propose the name nodular myofibroblastic hyperplasia of the mammary
      stroma as a more accurate name.

PMID- 12199758
TI  - Lymphoma of the breast: clinical and radiologic features with pathologic
      correlation in 28 patients.
AB  - The objective of this study was to determine the clinical and radiologic findings
      of lymphoma involving the breast, separately evaluating primary and secondary
      forms. We retrospectively reviewed the medical reports of 28 patients with
      lymphoma of the breast: 12 patients with primary lymphoma and 16 with secondary
      lymphoma. In primary lymphoma, mammography revealed a solitary mass (58.3%),
      multiple unilateral masses (8.3%), unilateral diffuse involvement (25%), and
      bilateral diffuse involvement (8.3%). The margins of masses were irregular (50%),
      partially defined (37.5%), and well defined (12.5%). The mean diameter of the
      masses was 4.6 cm. In secondary lymphoma, mammography revealed multiple masses
      (56.2%), solitary masses (12.5%), and diffuse unilateral breast involvement
      (31.2%). Their margins were irregular (18.1%), partially defined (27.2%), and
      well-defined (54.5%). The mean diameter of the masses was 2.8 cm. Cytologic
      examination (n = 13) was demonstrative of lymphomatous involvement in all cases.
      We observed an association between high-grade types of malignancy and a diffuse
      pattern of radiologic breast involvement. Masses in primary disease tended to
      have less-defined margins and greater diameters than those observed in secondary
      cases. Cytologic examination proved to be a useful diagnostic procedure in the
      evaluation of secondary disease. The involvement of the breast in extranodal
      lymphomas does not seem to affect the prognosis of the disease.

PMID- 12199759
TI  - Axillary metastasis from a malignant mullerian mixed tumor.

PMID- 12199760
TI  - Giant mammary lipoma.

PMID- 12199761
TI  - Metastatic "borderline" papillary ovarian tumor in an intramammary lymph node.

PMID- 12199762
TI  - Lipomatous fibroadenoma.

PMID- 12199763
TI  - Percutaneous endoscopy of an intracystic papilloma of the breast.
AB  - We present a new endoscopic procedure for the evaluation of intracystic papilloma
      of the breast. We suggest that the method is a potential alternative to open
      surgery.

PMID- 12199764
TI  - Internal mammary sentinel node metastases in an otherwise lymph-node negative
      breast cancer patient.
AB  - A 35 year old woman with biopsy proved breast cancer was submitted for sentinel
      node (SN) biopsy. Preoperative lymphoscintigraphy displayed both axillary and
      internal mammary (IM) uptake foci consistent with SNs. Full axillary dissection
      was completed because of a greater-than 2 cm primary lesion. Two axillary SNs
      were excised. An IM SN was also excised through the second intercostal space,
      with the aid of the gamma probe. Fourteen axillary nodes, including SNs, were
      negative, whereas the IM SN harbored several metastatic implants. Implications
      for staging, prognosis and further therapy of such IM-only positive sentinel
      nodes are discussed.

PMID- 12199766
TI  - Breast cancer status in Greece: 35-years experience.

PMID- 12199765
TI  - Radiation-induced osteosarcoma of the chest wall.
AB  - A case of radiation-induced sarcoma of the chest wall is reported. Twenty-seven
      years 11 months after orthovoltage radiotherapy of the right breast a 69-year-old
      woman developed a radiation-induced osteosarcoma of the right thoracic wall.
      Initial diagnosis has been T-cell lymphoma of the skin. The right breast was
      irradiated with tangential fields and a total dose of 40 Gy, 2 Gy/day, 5 days a
      week. Orthovoltage treatment was performed in two courses of 20 Gy, 3 months
      apart. The clinical appearance of the secondary sarcoma was a diffuse infiltrated
      area in the irradiated breast which seemed to be fixed to the chest wall.
      Magnetic resonance imaging (MRI) demonstrated a mass in the right anterior
      thoracic wall which destroyed the fourth to the sixth rib. The tumor infiltrated
      the thoracic wall, including subcutaneous tissue and pericardium, as well as
      extending into the subphrenic space. Biopsy of the lesion revealed a poorly
      differentiated osteosarcoma. The patient's general condition precluded surgical
      or chemotherapeutic intervention; she died due to a cerebral stroke 6 months
      later. This case fulfilled all criteria for radiation-induced sarcoma, as there
      was a prior history of radiotherapy, latency period of several years, development
      of sarcoma within the irradiated field, and histologic confirmation of sarcoma.

PMID- 12199767
TI  - Incipient breast cancer epidemic in new zealand.

PMID- 12199769
TI  - Graft-versus-host disease: the face of the aggressor.

PMID- 12199768
TI  - Severe autoimmune neutropenia associated with bone marrow sea-blue histiocytosis.

PMID- 12199770
TI  - Fifty years of idiopathic thrombocytopenic purpura (ITP): management of
      refractory itp in adults.

PMID- 12199771
TI  - Translation of cure for acute lymphoblastic leukaemia to all children.

PMID- 12199772
TI  - Splenectomy in mantle cell lymphoma with leukaemia: a comparison with chronic
      lymphocytic leukaemia.
AB  - We reviewed data on 63 patients with mantle cell lymphoma (MCL) with leukaemia (n
      = 16) and chronic lymphocytic leukaemia (CLL, n = 47), splenectomized over a 10
      year period. Primary indications for surgery were cytopenia(s) or autoimmune
      phenomena and progressive or refractory disease with splenomegaly. The spleens
      removed were on average larger in MCL (median 2.6 kg) than in CLL (1.0 kg).
      Splenectomy improved the blood counts in 62% of patients with MCL and 47% with
      stage C CLL, both with cytopenias. The MCL patients showed a decrease in the
      leucocytosis (medians 60.3-29.1 x 10(9)/l before and after splenectomy), whereas
      there was an increase in the leucocytosis in CLL (medians 24.2-44 x 10(9)/l).
      With a median follow up post splenectomy of 10 months (range: < 1-128), 18
      patients (four MCL and 14 CLL) have not required further therapy for up to 66
      months. We conclude that splenectomy is a useful treatment in MCL and advanced
      CLL for the correction of cytopenias, reducing the leucocyte count and allowing
      prolonged periods of clinical remission without therapy. Differences seen between
      MCL and CLL in spleen size, and in response of the leucocytosis suggest a central
      role for the spleen in the evolution of MCL with leukaemia.

PMID- 12199773
TI  - Enhanced killing of B lymphoma cells by granulocyte colony-stimulating factor
      primed effector cells and Hu1D10--a humanized human leucocyte antigen DR
      antibody.
AB  - Antibody-based approaches have become a novel treatment modality for lymphoma
      patients. Humanized 1D10 (Hu1D10; Remitogen) is among the antibodies that are
      currently under evaluation in phase II clinical trials in lymphoma patients. The
      1D10 antibody is directed against a polymorphic epitope on the beta-chain of
      human leucocyte antigen (HLA) class II. We found expression of the 1D10 epitope
      on B cells and monocytes from approximately 50% of healthy donors. Analyses of
      1D10 expression on malignant cells revealed that approximately half of the HLA
      class II-positive haematological malignancies expressed the 1D10 epitope. In
      whole blood antibody-dependent cellular cytotoxicity (ADCC) assays, Hu1D10 was
      more effective than rituxan in killing malignant ARH-77 B cells. Interestingly,
      Hu1D10-mediated lymphoma cell lysis was significantly enhanced when blood from
      granulocyte colony-stimulating factor (G-CSF)-treated patients was compared with
      blood from healthy controls. Analyses of the relevant effector cell populations
      revealed that FcgammaRI (CD64)-positive polymorphonuclear cells were critical for
      enhanced Hu1D10-mediated lymphoma killing during G-CSF therapy, while the same
      effector cell population induced only marginal lysis with rituxan. Furthermore,
      Hu1D10 was highly effective in inducing apoptosis in primary lymphoma cells from
      B chronic lymphocytic leukaemia patients. These preclinical results form the
      basis for a phase I/II clinical trial of Hu1D10 in combination with G-CSF.

PMID- 12199774
TI  - CD40L stimulation enhances the ability of conventional metaphase cytogenetics to
      detect chromosome aberrations in B-cell chronic lymphocytic leukaemia cells.
AB  - Conventional metaphase cytogenetics underestimates the frequency of specific
      chromosome aberrations in B-cell chronic lymphocytic leukaemia (B-CLL) as a
      result of the very low proliferative activity of these cells in vitro. New
      molecular approaches, such as fluorescence in situ hybridization (FISH) or
      comparative genomic hybridization (CGH), may circumvent this problem, at least in
      part, but these techniques are either strongly dependent on the knowledge of
      candidate regions or detect only unbalanced aberrations. In the present study, we
      analysed 27 B-CLL peripheral blood samples by metaphase cytogenetics after CD40
      ligand (CD40L)-induced cell cycle stimulation. In comparison with the
      simultaneous use of B-cell mitogens such as 12-O-tetradecanoylphorbol-13-acetate
      (TPA), lipopolysaccharide (LPS) and pokeweed mitogen (PWM), CD40L stimulation of
      B-CLL cells induced a threefold increase in metaphases amenable to analysis by
      conventional cytogenetics. The analysis of these metaphases confirmed all genetic
      abnormalities detected by FISH. Moreover, CD40L-enhanced cytogenetics revealed
      complex karyotypic aberrations in 11 out of 27 patients (41%). In one case, a
      balanced translocation t(11;16)(p15;p13.1), so far unreported in B-CLL, was
      detected. Taken together, the results of our study show the potential of CD40L
      enhanced metaphase cytogenetics to detect more and new chromosome aberrations in
      B-CLL.

PMID- 12199775
TI  - Defective assembly of the B-cell receptor chains accounts for its low expression
      in B-chronic lymphocytic leukaemia.
AB  - B-cell chronic lymphocytic leukaemia (B-CLL) characteristically displays low
      amounts of B-cell receptor (BCR), which mainly consists of the heterodimer
      CD79a/CD79b bound non-covalently with the surface immunoglobulin (SIg). This
      heterodimer is required for SIg expression and BCR signalling. To better define
      the mechanisms related to low BCR expression, we have investigated transcription,
      protein synthesis, assembly and transport of the BCR in B-CLL cells. Our results
      demonstrated that: (1) there was no major defect in transcriptional expression of
      the B29 (CD79b) gene; (2) the BCR components were intracellularly detected, thus
      adequately synthesized, in almost all patients; (3) neither a genetic defect in
      the transmembrane region of SIg, which associated with CD79a/CD79b, nor a genetic
      abnormality in the chaperone protein calnexin that is involved in folding and
      assembly of the BCR were found; (4) a constant defect in the assembly of IgM and
      CD79b chains occurred leading to abnormal accumulation of both chains in
      different intracellular compartments; (5) in a majority of CLL patients all of
      the nascent IgM failed to be processed into mature chains and remained unsuitable
      for transport. These findings demonstrated that a post-transcriptional defect
      located at the BCR intracellular assembly and/or trafficking levels could be
      involved in its low surface expression in B-CLL.

PMID- 12199776
TI  - A descriptive study of randomized trials of treatments for childhood acute
      lymphoblastic leukaemia.
AB  - This report presents a historical and descriptive account of randomized trials in
      childhood leukaemia since the earliest such studies in the 1960s. It focuses on
      trials that began before 1988, making use of the register of trials developed for
      a systematic review of treatments for acute lymphoblastic leukaemia in children.
      The number of randomized trials starting each year increased from one or two in
      the 1960s to an annual average of five or six in the 1980s. However trials
      remained relatively small, with more than half of all randomizations accruing
      less than 200 patients and only five having more than 1000. Most trials were
      published more than once.

PMID- 12199777
TI  - Increased angiogenesis in bone marrow of children with acute lymphoblastic
      leukaemia has no prognostic significance.
AB  - The importance of angiogenesis for the growth and viability of solid tumours has
      been established. Similarly, prognostic information may be gained from the extent
      of angiogenesis in these tumours. Haematopoietic malignancies should have equal
      requirements for angiogenesis and important prognostic information may be derived
      from quantification of bone marrow angiogenic activity. We retrospectively
      investigated 82 bone marrow trephine biopsies from 41 children with acute
      lymphoblastic leukaemia (ALL) at diagnosis and following treatment. Nine normal
      bone marrow trephines from age-matched children were also analysed as controls.
      The microvessels were stained immunohistochemically with anti-Factor VIII-related
      antigen (antivWF) and antithrombomodulin (anti-THR). Angiogenesis was quantified
      manually by two independent observers and was highly reproducible (Pearson's r =
      0.91). Staining with anti-vWF and anti-THR was highly specific for microvessels
      and thetwo stains closely correlated (r = 0.68). Microvessel densities (MVD) at
      presentation were significantly increased in the majority of patients in
      comparison with controls (P < 0.0001) and MVD dropped towards normal in remission
      (P < 0.0001). Of interest, the difference in total vessel counts between
      leukaemic and normal/remission marrows was contributed solely by small
      microvessels. There was no significant difference in MVD at presentation or
      remission from children in poor prognostic groups or those who subsequently
      relapsed. Similarly, we could not find an association with age, sex, cytogenetic
      abnormality or disease phenotype.

PMID- 12199778
TI  - Risk-directed treatment of infant acute lymphoblastic leukaemia based on early
      assessment of MLL gene status: results of the Japan Infant Leukaemia Study
      (MLL96).
AB  - We studied the effectiveness of risk-directed therapy for infants younger than 13
      months of age with acute lymphoblastic leukaemia (ALL). Fifty-five infants were
      assigned to different treatment programs (from December 1995 to December 1998) on
      the basis of their MLL gene status at diagnosis. Forty-two cases (76.3%) had a
      rearranged MLL gene (MLL+) and were treated with remission induction therapy
      followed by sequential intensive chemotherapy, including multiple genotoxic
      agents (MLL9601 protocol). Haematopoietic stem cell transplantation (HSCT) was
      attempted if suitable donors were available. Thirteen infants (23.7%) were
      classified as MLL- and treated for 2.5 years with intensive chemotherapy for high
      risk B-ALL (MLL9602 protocol). Complete remission was induced in 38 of the 42
      infants (90.5%) with MLL+ ALL and in all 13 patients (100%) with MLL- disease. In
      the MLL+ subgroup, the estimated event-free survival (EFS) rate at 3 years post
      diagnosis was 34.0% +/- 7.5%, compared with 92.3% +/- 7.4% in the MLL- subgroup
      (overall comparison, P = 0.001 by log-rank analysis). Both age less than 6 months
      (hazard ratio = 6.87, 95% CI = 0.91-52.3; P = 0.013) and central nervous system
      (CNS) involvement at diagnosis (hazard ratio = 2.92 95% CI = 1.29-6.63; P =
      0.015) were significant independent predictors of an inferior outcome. These
      findings indicate a strategic advantage in classifying infant ALL as either MLL+
      or MLL- early in the clinical course and selecting therapy accordingly. Standard
      chemotherapy for high-risk B-lineage ALL appeared adequate for MLL- cases. Novel
      therapeutic initiatives are warranted for infants with MLL+ disease, particularly
      those with initial CNS leukaemic involvement or age less than 6 months, or both.

PMID- 12199780
TI  - The use of anti-T-cell receptor-Vbeta antibodies for the estimation of treatment
      success and phenotypic characterization of clonal T-cell populations in cutaneous
      T-cell lymphomas.
AB  - Sezary syndrome and Mycosis fungoides are the most common forms of cutaneous T
      cell lymphomas. To assess the response to different therapies especially in
      Sezary syndrome, it is helpful to monitor the percentage of circulating tumour
      cells in the blood. The use of T-cell receptor (TCR)-Vbeta specific monoclonal
      antibodies provides a suitable tool for detecting Sezary cells. In this study, we
      analysed the levels of clonal CD4+Vbeta+ cells of seven patients with various
      treatment modalities using flow cytometry and investigated the immunophenotype of
      the clonal cells by double staining with a panel of antibodies recognizing
      lymphatic surface markers. Additionally, a polymerase chain reaction-denaturing
      gradient gel electrophoresis assay was performed on clonal CD4+Vbeta2+ cells,
      showing that these cells carry a Vgamma10/11, JgammaP1/2 TCR rearrangement.
      Follow-up studies revealed close association of the Vbeta+ clone developmentwith
      the clinical response to different therapiesinsixpatients. Intwo cases, the
      CD4+Vbeta+ cells decreased accompanied by partial regression or even complete
      remission. In four cases, a stable or increasing clonal CD4+Vbeta+ population
      reflected well a stable or progressing course of the disease. Double staining of
      Vbeta+ cells revealed the following pattern, CD3+, CD5+, CD7+, CD28+, CD80-,
      CD86+ and human leucocyte antigen (HLA) class I+. In contrast, HLA-DR was
      heterogeneously expressed. We conclude that identification and monitoring of
      CD4+Vbeta+ clonal T cells by fluorescence-activated cell sorting with double
      staining is a suitable method to assess clinical responses to different
      therapies.

PMID- 12199779
TI  - Molecular characterization of a new recombination of the SIL/TAL-1 locus in a
      child with T-cell acute lymphoblastic leukaemia.
AB  - Deletions involving the SIL-TAL-1 locus are seen in 15% of T-acute lymphoblastic
      leukaemias (T-ALL). To date, seven deletions have been described, spreading over
      90 kb of chromosome 1, fusing SIL to the TAL-1 gene and resulting in over
      expression of TAL-1. During the diagnostic screening of the TAL-1 deletion in 176
      T-ALL patients, we identified one case showing a new SIL rearrangement. A novel
      fusion transcript was identified between the SIL exon 1a and an unknown sequence
      (633-cDNA). Polymerase chain reaction (PCR) screening of a human cDNA library
      confirmed the existence of this transcript. Using long-distance PCR on patient
      DNA, we obtained a genomic fragment containing SIL exon 1b, a portion of intron
      1b, an unknown sequence and the 633 sequence. Using DNA from healthy donors, a
      partial genomic map of 633-DNA was found to be identical to the restriction map
      of the PCR fragment amplified from patient DNA. To define the chromosomal origin
      of 633-DNA, a YAC human genomic library was screened. Two clones containing 633
      DNA were found, mapping to chromosomal region 1p32 and both contained SIL and TAL
      1 sequences. By searching GenBank, we identified PAC RP1-18D14 which contains
      SIL, TAL-1 and 633-DNA, confirming this novel rearrangement as a new deletion of
      the SIL/TAL-1 locus.

PMID- 12199781
TI  - Abnormal WT1 expression in the CD34-negative compartment in myelodysplastic bone
      marrow.
AB  - In normal bone marrow, WT1 expression is restricted to CD34+ cells. We assessed
      WT1 mRNA expression levels with quantitative, real-time reverse transcription
      polymerase chain reaction in normal, myelodysplastic (MDS) and secondary acute
      myeloid leukaemia (sAML) bone marrow subfractions, based on differentiation
      status. The highest WT1 expression was observed in the primitive CD34+ rhodamine
      123 (rho) dull cells, both in healthy donors and MDS or sAML patients. In
      contrast to normal CD34-negative bone marrow cells, WT1 was present in CD34
      negative bone marrow cells in 12 out of 13 MDS patients and two sAML samples.
      Further analysis of this aberrant WT1 expression was performed in the CD34
      negative subfractions of three MDS patients. In one of these, WT1 expression was
      found exclusively in the erythroid cells. This patient was completely transfusion
      dependent and showed morphological dyserythropoiesis. In another MDS patient, WT1
      expression was found in a non-erythroid compartment. We conclude that abnormal
      WT1 expression may contribute to the disturbed differentiation of haematopoietic
      cells in MDS patients.

PMID- 12199782
TI  - Methylation is an inactivating mechanism of the p16 gene in multiple myeloma
      associated with high plasma cell proliferation and short survival.
AB  - In order to gain further insights into the role of the p16 gene in cell cycle
      regulation and the prognostic implications of its inactivation, we investigated
      the methylation status of the p16 gene in 98 untreated patients using a
      polymerase chain reaction assay based on the inability of some restriction
      enzymes to digest methylated sequences. Forty-one patients showed a p16
      methylated gene (42%). The percentage of S-phase plasma cells (PC) in these
      patients was almost three times higher than in those with an unmethylated p16
      gene (4.16% +/- 3.37%vs 1.5% +/- 1.41%, P < 0.001). The presence of p16
      methylation also correlated with both elevated beta2-microglobulin serum levels
      and high C-reactive protein values. Patients with a p16 methylated gene had
      shorter overall and progression-free survival than those patients without p16
      methylation. However, this feature did not retain independent prognostic
      influence on multivariate analysis, probably due to its association with the S
      phase PC, which had more potent statistical significance in the Cox model. These
      findings showed methylation of the p16 gene was a frequent event inMM patients at
      diagnosis, and was associated with an increased proliferative rate of plasma
      cells and a poor prognosis, indicating an important role for p16 gene in the cell
      cycle regulation of multiple myeloma tumour cells, and thus in the clinical
      outcome of the disease.

PMID- 12199783
TI  - Both hypodiploidy and deletion of chromosome 13 independently confer poor
      prognosis in multiple myeloma.
AB  - Complete or partial deletion of chromosome 13 or translocations involving 13q
      (delta13) by conventional cytogenetic analysis confers a poor prognosis in
      multiple myeloma (MM) patients, even with timely application of tandem autologous
      transplants. It was recently suggested that the prognostic significance of
      delta13 is related to its frequent association with hypodiploidy but by itself
      does not have a poor prognostic significance. We therefore analysed our
      experience in 1475 consecutive MM patients in whom we intended treatment with
      tandem transplants after a melphalan-based conditioning regimen. Patients with
      abnormal cytogenetic analysis were grouped into hypodiploid/hypotetraploid,
      pseudodiploid and hyperdiploid groups, according to their modal chromosome
      number. Their event-free and overall survival were compared with those of
      patients with a normalkaryotype. Both hypodiploidy and delta13 were found to
      independently confer poor prognosis in MM patients. Furthermore, these parameters
      in combination with easily obtained pretransplant levels of beta-2 microglobulin
      and albumin define three groups of MM patients with clearly distinct outcomes.

PMID- 12199784
TI  - Intensive chemotherapy in patients with chronic myelogenous leukaemia (CML) in
      accelerated or blastic phase--a report from the Swedish CML Group.
AB  - In attempting to restore the chronic phase (CP) of chronic myelogenous leukaemia
      (CML), the Swedish CML group utilized an intensive chemotherapy protocol for 83
      patients (aged 16-79 years) in accelerated (AP, n = 22) or blastic phase (BC, n =
      61). Most patients received a combination of mitoxantrone (12 mg/m2/d) and
      etoposide (100 mg/m2/d) together with cytosine arabinoside (1 g/m2 b.i.d) for 4
      d. Overall, 39 patients (47%) achieved a second CP (CP2)/partial remission (PR).
      Responding patients < 65 years were eligible for ablative chemotherapy followed
      by an allogeneic (SCT) or a double autologous stem cell transplant (ASCT).
      Seventeen of 34 responders < 65 years failed to proceed to transplantation as a
      result of early disease progression (n = 15) or disease-related complications (n
      = 2). The remaining 17 patients underwent SCT (n = 9; including four unrelated
      donor SCT) or ASCT (n = 8). Only one of the eight ASCT patients had a second
      ASCT; the remaining seven failed because of progression (n = 5) or hypoplasia (n
      = 2). The median duration of CP2/PR was 6 months (range 1-72 months). Five
      patients achieved a longer CP2/PR than CP1. The 1 year survival was 70% for
      SCT/ASCT patients (median survival 21 months), 50% for responding patients
      overall, but only 7% for non-responders (P < 0.001). Three SCT/ASCT patients are
      long-term survivors (65+, 66+ and 73+ months). In conclusion, approximately half
      of the patients achieved a CP2/PR after intensive chemotherapy, with a clear
      survival advantage for responders vs non-responders. Subsequent SCT/ASCT was
      feasible for half of the responders (< 65 years), and one individual underwent
      double ASCT. Novel therapeutic options for CML patients in AP/BP are needed.

PMID- 12199786
TI  - Gene expression analysis of 1,25(OH)2D3-dependent differentiation of HL-60 cells:
      a cDNA array study.
AB  - The alterations in gene expression associated with 1,25(OH)2D3-induced
      differentiation of HL-60 cells were studied in order to identify potential
      targets for further investigation of the genetic basis of acute myeloid
      leukaemia. Atlas human haematology filters, including 406 genes (Clontech), were
      used to study gene expression in response to 1,25(OH)2D3 (concentration, 5 x 10-8
      mol/l) for 24 and 72 h. Compared with untreated cells, expression differences
      were found in 43 genes. Downregulated genes at both time-points were: IL2RA,
      CMYC, NPM, DEK, AF4, FLI1, htlf, MNDA, BCR, IKAROS, BPI and NFAT4. Upregulated
      genes at both time-points were IL1B, CD14 and MCL1. CD55, CD58, IRF2, CREB1,
      ATF4, RAC1, TIAR, KIAA0053, BAT2, BTK, RCK, EV12B and EDN were downregulated at
      24 h, while SPI1, MKK3, BTG1 and IL8 were upregulated. At 72 h the upregulated
      genes were IL1RA, IL2RG, CXCR4, SCYA1, SCYA3, SCYA4, SCYA5, SCYA22, ANX2, CD83
      and UPAR. cDNA array results were confirmed on randomly selected genes using
      quantitative real-time polymerase chain reaction for three upregulated (CXCR4,
      IL1B and CD14) and three downregulated (DEK, AF4 and FLI1) genes. Gene expression
      analysis after differentiation induction may provide a tool to study the roles of
      DEK, AF4 and FLI1 in cell proliferation and differentiation. To demonstrate the
      genes that initiate differentiation, sequential gene expression analysis has to
      be performed during the first 24 h of the differentiation process.

PMID- 12199785
TI  - Hodgkin and Reed-Sternberg cells express functional c-kit receptors and interact
      with primary fibroblasts from Hodgkin's disease-involved lymph nodes through
      soluble and membrane-bound stem cell factor.
AB  - Classic Hodgkin's disease (cHD) is a lymphoid neoplasia characterized by few
      malignant Hodgkin and Reed-Sternberg (H-RS) cells, embedded in an abundant
      background of non-tumour cells. We have previously demonstrated the expression in
      primary H-RS cells of the receptor tyrosine kinase (RTK) c-kit; here we describe
      its functional role in the cross-talk between H-RS cells themselves with
      neighbouring cell populations. In particular, we analysed the expression of c-kit
      and its ligand stem cell factor (SCF) in a panel of HD-derived cell lines and
      fibroblasts from HD-involved lymph nodes (HDF). While c-kit was expressed by HD
      derived cell lines, usually in the absence of SCF, this latter molecule, in its
      soluble and/or membrane-bound (mb) form, was in turn expressed at a high level by
      primary HDF. In vitro adhesion between HD-derived cell lines and HDF was mainly
      mediated by c-kit/SCF interactions, and this phenomenon was significantly
      inhibited by an excess of soluble SCF or by neutralizing anti-c-kit monoclonal
      antibodies. Furthermore, both soluble and mb-SCF increased growth and colony
      survival of HD-derived cell lines; these effects were significantly enhanced upon
      co-stimulation of H-RS cells with interleukin 9. Finally, soluble SCF was able to
      partially rescue H-RS cells from apoptosis induced by serum starvation. Taken
      together, our data indicated the expression of functional c-kit receptor by H-RS
      cells and suggests a role of SCF in the pathobiology of cHD.

PMID- 12199787
TI  - Sex ratios and the risks of haematological malignancies.
AB  - Although the sex of an individual confers one of the greatest of the known risks
      for contracting leukaemia and lymphomas, very little attention is paid to these
      risks. It is the purpose of this paper to stimulate further research in this
      area. The sex rate ratios are presented for the commoner haematological
      malignancies. The male excess in the lymphoid cancers is most marked in the
      youngest age group in non-Hodgkin's lymphoma and Hodgkin's disease, while acute
      lymphoblastic leukaemia shows equal sex ratios in the childhood peak. Both
      chronic lymphocytic leukaemia and lymphocytic lymphoma display an unusual
      pattern, hitherto undescribed, with a large male excess specific to the 40s and
      60s age groups. The myeloid sex ratios are all characterized by slight female
      excess in early adulthood followed by marked male excess. The reasons for these
      patterns are discussed.

PMID- 12199788
TI  - Effect of anti-CD20 (rituximab) on resistant thrombocytopenia in autoimmune
      lymphoproliferative syndrome.
AB  - Fas (CD95) plays an important role in apoptosis. Patients with defects in Fas
      have an autoimmune lymphoproliferative syndrome (ALPS) characterized by
      lymphadenopathy, autoimmune cytopenias and an increased incidence of lymphomas.
      There are approximately 70 known cases described worldwide. The autoimmune
      cytopenias are difficult to treat in this group. We describe a patient with a
      defect in the death domain of the FAS molecule who had autoimmune
      thrombocytopenia resistant to conventional therapy but which responded to a
      combination of rituximab and vincristine.

PMID- 12199789
TI  - Acquired trisomy 21 and distinct clonal evolution in acute megakaryoblastic
      leukaemia in young monozygotic twins.
AB  - An intrauterine origin of childhood acute lymphoblastic leukaemia (ALL) was
      proven by the identical clonotypic gene rearrangement in the concordant
      leukaemias of monozygotic twins, arising from a single clonogenic progeny. The
      monozygotic twins, presented at the age of 22 months with acute megakaryoblastic
      leukaemia (AML-M7) in one and myelodysplasia transformed to AML-M7 in the other.
      Leukaemic cells in both twins carried trisomy 21 and additional different clonal
      evolution changes of del(20q) in the first twin and trisomy 8 in the second. AML
      M7 of late infancy with trisomy 21 may be included in the leukaemias of
      intrauterine origin, possibly a result of genotoxic insult.

PMID- 12199790
TI  - Plasminogen activator inhibitor-1 is an independent diagnostic marker as well as
      severity predictor of hepatic veno-occlusive disease after allogeneic bone marrow
      transplantation in adults conditioned with busulphan and cyclophosphamide.
AB  - We attempted to identify the diagnostic markers and severity predictors of
      hepatic veno-occlusive disease (VOD) in 115 adult patients who were uniformly
      conditioned with busulphan and cyclophosphamide and who underwent allogeneic bone
      marrow transplantation (BMT). A diagnosis of VOD was made according to clinical
      criteria. Severity of VOD was classified as mild, moderate or severe. Various
      haemostatic parameters were determined at five time points (d -7, 0, 7, 14 and
      21). Using clinical and haemostatic parameters, we developed multivariate models
      to identify diagnostic markers as well as severity predictors of VOD. Of the 115
      patients included in the study, 50 (43.5%) developed VOD. Twenty-nine had mild
      VOD, 13 moderate and 8 severe. Multiple logistic regression models showed that
      plasminogen activator inhibitor-1 (PAI-1) antigen (P = 0.029), percentage change
      of body weight (P = 0.001) and bilirubin (P < 0.001) were independent marker
      variables for the occurrence of VOD, and PAI-1 antigen (P = 0.030) and bilirubin
      (P = 0.049) were independent marker variables for the occurrence of severe VOD.
      Our study suggests that PAI-1 antigen can be used as a diagnostic marker as well
      as a severity predictor of VOD after allogeneic BMT.

PMID- 12199791
TI  - CD34+-enriched peripheral blood progenitor cells from unrelated donors for
      allografting of adult patients: high risk of graft failure, infection and relapse
      despite donor lymphocyte add-back.
AB  - Fifty-one adults with haematological malignancies were transplanted with CD34+
      selected peripheral blood progenitor cells (PBPC) from unrelated donors. The
      conditioning protocol contained total body irradiation (n = 17) or combinations
      of busulphan and other alkylating agents (n = 34). Antithymocyte globulin was
      infused in all patients. The median number of CD3+ T cells infused with the graft
      after purification with the Isolex 300 system in the first cohort of 18 patients
      was 2.1 x 10(5)/kg. Prophylactic donor lymphocyte infusion (DLI) containing 1 x
      10(5) CD3+ T cells was performed on d 21 in the following 33 patients who had
      received PBPC purified by the CliniMACS system. Early graft failure occurred in
      8/51 patients (16%). After a median follow-up of 31 months (range 8-60), the
      probability of disease-free survival (DFS) was 36% for the whole group. Reasons
      for death were opportunistic infections (n = 15), graft-versus-host disease
      (GvHD, n = 7) and relapse (n = 4). Pre-transplant factors with significant impact
      on DFS were cytomegalovirus status and risk category of underlying disease. The
      occurrence of graft failure or GvHD was associated with poor outcome. Recipients
      of CD34+-selected PBPC from unrelated donors are at high risk of infectious
      complications, relapse and graft failure which cannot be prevented by early
      reinfusion of unmodified donor lymphocytes.

PMID- 12199792
TI  - Influence of post-transplant recombinant human granulocyte colony-stimulating
      factor administration on peritransplant morbidity in patients undergoing
      autologous stem cell transplantation.
AB  - This study evaluated of the effect of post-transplant recombinant human
      granulocyte colony-stimulating factor (rhG-CSF) administration on the parameters
      of peritransplant morbidity. Three sequential and consecutive cohorts of 20
      patients each received either post-transplant rhG-CSF at a dose of 5 micro g/kg/d
      i.v. in the morning, starting on d 0, d 5, or no rhG-CSF. Patients who received
      rhG-CSF starting on d 0 and 5 recovered granulocytes more rapidly than those not
      receiving rhG-CSF (P < 0.001 for ANC >or= 0.5 and 1 x 10(9)/l). RhG-CSF
      administration was not significantly associated with more rapid platelet
      engraftment. RhG-CSF administration starting on d 0 and 5 was significantly
      associated with a decreased duration of fever (P = 0.002 and 0.001 respectively),
      antibiotic administration (P < 0.001 and 0.006 respectively) and shorter
      hospitalization (P < 0.001 and 0.001 respectively) compared with the reference
      group. There was no difference between the d 0 and d 5 arms regarding the
      parameters of peritransplant morbidity. In conclusion, rhG-CSF administration was
      associated with a faster granulocyte recovery, shorter hospitalization, and
      shorter period of fever and non-prophylactic antibiotic administration. This
      study also showed that starting rhG-CSF administration on d 5 may be as effective
      as d 0 on the clinical outcome and may be an economical approach in routine
      clinical practice in this cost-conscious era.

PMID- 12199793
TI  - Thrombotic thrombocytopenic purpura after allogeneic stem cell transplantation: a
      survey of the European Group for Blood and Marrow Transplantation (EBMT).
AB  - A survey was carried out among the European Group for Blood and Marrow
      Transplantation (EBMT) centres to determine the incidence, risk factors,
      treatment and outcome of thrombotic thrombocytopenic purpura (TTP) following
      allogeneic haematopoietic stem cell transplantation. TTP was defined as the
      simultaneous occurrence of red cell fragmentation, laboratory findings of
      haemolysis, red cell transfusion requirement and de novo or persistent
      thrombocytopenia caused by consumption, in the absence of disseminated
      intravascular coagulation. Forty-five centres reported all patients (n = 406)
      transplanted between July and December 1996. Twenty-three patients developed TTP;
      the risk of developing TTP was 6.7% at 2 years (95% CI: 4.1% to 9.3%). The median
      time of onset was 44 d (range 13-319) post transplantation. Significant risk
      factors for the development of TTP were female gender (P = 0.005) and an
      unrelated donor (P = 0.046). To treat TTP, cyclosporin administration was
      discontinued in 10 cases, plasma exchanges were performed in five cases and 12
      patients received plasma infusions without plasma exchange. TTP resolved in 13 of
      the 23 patients (57%). The only factor predictive of resolution of TTP was the
      absence of nephropathy. Seven patients (30%) were alive at follow-up of 38-45
      months from the onset of TTP. Sixteen patients died; the causes were multiple,
      only three patients had TTP as a central factor. The median time to death was 41
      d (range 1-762 d) from the onset of TTP. TTP is a relatively frequent
      complication of allogeneic stem cell transplantation and it is associated with
      high mortality, though death is usually caused by multiple factors.

PMID- 12199794
TI  - Identification of early antigen BZLF1/ZEBRA protein of Epstein-Barr virus can
      predict the effectiveness of antiviral treatment in patients with post-transplant
      lymphoproliferative disease.
AB  - Epstein-Barr virus (EBV)-associated B-cell lymphoproliferations may arise in
      solid organ transplant recipients. In these patients, an insufficient control of
      EBV-infected B cells commonly occurs. Antiviral treatment against EBV may
      represent a causal, relatively low-toxic treatment option. Treatment with
      foscarnet, an inhibitor of viral-DNA polymerase, in three patients with EBV
      associated post-transplant lymphoproliferative disease (PTLD) after heart (n = 2)
      and heart/kidney transplantation (n = 1), who did not respond to, or were not
      eligible for reduction of immunosuppression, resulted in complete remission (48+,
      27 and 15 months respectively). Response of PTLD to antiviral treatment
      correlated with the expression of lytic phase antigen BZLF1/ZEBRA protein, an
      early antigen of lytic EBV-activity, in the biopsied PTLD specimens.

PMID- 12199795
TI  - The impact of transfusion of leucodepleted platelet concentrates on
      cytomegalovirus disease after allogeneic stem cell transplantation.
AB  - The impact of transfusion of leucodepleted platelet concentrates (PCs) on
      cytomegalovirus (CMV) disease was assessed in 215 allogeneic (145 unrelated and
      70 related donor) transplants over 3 years. In 43%, both donor and patient were
      CMV seronegative (CMV-/-). All received CMV-seronegative red cells and random
      leucodepleted PCs. No CMV disease occurred in any CMV-/- (low risk) transplant.
      CMV infection occurred in 31 seropositive patients (26%); 13 died and five deaths
      were attributable to CMV disease. When compared with historical controls, who
      received CMV-seronegative PCs, we found no difference in transfusion-acquired CMV
      in the current cohort.

PMID- 12199796
TI  - Treatment of high-risk acute myelogenous leukaemia by myeloablative
      chemoradiotherapy followed by co-infusion of T cell-depleted haematopoietic stem
      cells and culture-expanded marrow mesenchymal stem cells from a related donor
      with one fully mismatched human leucocyte antigen haplotype.
AB  - A 20-year-old woman with high-risk acute myelogenous leukaemia was transplanted
      with granulocyte colony stimulating factor (G-CSF)-mobilized peripheral blood
      CD34+ haematopoietic stem cells and bone-marrow-derived mesenchymal stem cells
      (MSC) from her human leucocyte antigen haplotype-mismatched father after
      myeloablative conditioning therapy. The patient engrafted rapidly and had no
      acute or chronic graft-versus-host disease. Since transplantation, the patient
      has shown an enduring trilineage haematological complete response without any
      evidence of leukaemia relapse at 31 months. We suggest that MSC can be used
      effectively for genetically haploidentical haematopoietic stem cell
      transplantation for acute leukaemia.

PMID- 12199797
TI  - Many alphaIIbbeta3 autoepitopes in chronic immune thrombocytopenic purpura are
      localized to alphaIIb between amino acids L1 and Q459.
AB  - In chronic immune thrombocytopenic purpura (ITP), autoantibodies bind to platelet
      surface proteins, particularly alphaIIb, resulting in platelet destruction by the
      reticulo-endothelial system. In order to better localize the autoepitopes on
      alphaIIb, we studied the binding of antibodies to Chinese hamster ovary (CHO)
      cells expressing either alphaIIbbeta3 or alphaIIb-alphavbeta3 chimaeras in which
      a segment of alphaIIb (either amino acids L1-Q459, L1-F223 or F223-Q459) was
      substituted for that portion of alphav. We evaluated platelet-associated
      autoantibodies from 14 ITP patients with alphaIIb-dependent antibodies. Ten of 14
      bound to alphaIIb (L1-Q459)-alphavbeta3, showing that autoepitopes were often
      localized to this region of alphaIIb. In addition, each of the autoantibodies
      binding to alphaIIb (L1-Q459)-alphavbeta3, also bound to CHO cells expressing
      either alphaIIb(L1-F223)-alphavbeta3 or alphaIIb(F223-Q459)-alphavbeta3). In two
      of the three eluates tested, > 95% of the autoantibody binding to alphaIIb could
      be adsorbed using CHO cells expressing any of the three chimaeras, showing that
      the epitope(s) have contact points on either side of amino acid F223; in the
      third eluate, only a portion ( approximately 40%) could be adsorbed by the
      chimaeric cell lines showing that, in this patient, an additional antibody was
      also present, directed to a site distal to amino acid Q459. The remaining four
      eluates bound to CHO cells expressing alphaIIbbeta3 but to none of the chimaeras,
      suggesting that these epitopes are also distal to amino acid Q459. We conclude
      that the binding of many anti-alphaIIbbeta3 autoantibodies is dependent on the
      presence of alphaIIb amino acids L1-Q459.

PMID- 12199798
TI  - Incidence and clinical relevance of heparin-induced antibodies in patients with
      deep vein thrombosis treated with unfractionated or low-molecular-weight heparin.
AB  - The frequency of heparin-induced thrombocytopenia (HIT) varies between different
      clinical treatment settings and remains unknown for patients treated with
      unfractionated (UFH) or low-molecular-weight heparin (LMWH) because of deep vein
      thrombosis. In this multicentre, open-label study, 1137 patients with deep vein
      thrombosis were randomly assigned to UFH for 5-7 d, reviparin, a LMWH, for 5-7 d
      (short-treated group) or reviparin for 28 d (long-treated group). Heparin
      platelet factor 4 antibodies (HPF4-A) were determined on d 5-7 and d 21. Heparin
      induced thrombocytopenia was defined by clinical evaluation. Two patients in the
      UFH group (incidence: 0.53%, 95% confidence interval (CI): 0.06-1.91) and two
      patients in the long-treated LMWH group (incidence: 0.53%, 95% CI: 0.06-1.92) had
      HIT, while no HIT was observed in the short-treated LMWH group. Pulmonary
      embolism developed in one of the HIT-patients, who had HPF4-A and was treated
      with UFH. On d 5-7 the incidence of HPF4-A was 9.1% in the UFH group, 2.8% in the
      short-treated LMWH group and 3.7% in the long-treated LMWH group, with a
      significant increase to 20.7% in the UFH group and to 7.5% in the long-treated
      LMWH group on d 21. Therefore the incidence of HPF4-A and heparin-induced
      thrombocytopenia was lower in patients treated with LMWH compared with UFH for
      the same duration of treatment.

PMID- 12199799
TI  - A Ser752-->Pro substitution in the cytoplasmic domain of beta3 in a Glanzmann
      thrombasthenia variant fails to prevent interactions between the alphaIIbbeta3
      integrin and the platelet granule pool of fibrinogen.
AB  - A Glanzmann thrombasthenia variant with a beta3 Ser752-->Pro cytoplasmic domain
      substitution has platelets that fail to aggregate or bind soluble fibrinogen (Fg)
      after activation. Despite this, Fg is normally present in the alpha-granules. We
      have used immunoelectron microscopy to examine the reactivity of Fg with the
      different pools of alphaIIbbeta3 in the patient's platelets. Immunogold labelling
      was performed on cryosections using an anti-ligand-induced binding site (LIBS)
      monoclonal antibody (mAb), which binds to alphaIIbbeta3 only when Fg is bound, or
      a mixture of two anti-receptor-induced binding site (RIBS) mAbs that specifically
      recognize receptor-bound Fg. Labelling of the alpha-granule membrane and channels
      of the surface-connected canalicular system in unstimulated platelets confirmed
      that the mutated alphaIIbbeta3 retains the capacity to transport Fg. When the
      patient's platelets were stimulated with ADP in the presence of Fg, as expected
      there was a much-decreased activation of surface-exposed alphaIIbbeta3. However,
      thrombin-induced activation was associated with both secretion and a rapid
      increase in the labelling of internal membrane systems by anti-RIBS and anti-LIBS
      mAbs, with mobilization of the internal Fg pool. Yet labelling on the surface of
      the patient's platelets was transient. Our studies implied that alphaIIbbeta3 in
      platelets may bind fibrinogen in different activation states and that this
      patient specifically lacked high-affinity binding.

PMID- 12199800
TI  - Enhancement of human platelet activation by the combination of low concentrations
      of collagen and rabbit anticardiolipin antibodies.
AB  - Low concentrations of collagen and anticardiolipin antibodies (ACLA), which were
      raised in rabbits by immunization with cardiolipin (CL), co-operatively activated
      human gel-filtrated platelets (GFP). GFP activated by adding ACLA 5 min prior to
      collagen (ACLA + Col) showed strong responses in cytosolic Ca2+ mobilization and
      cell aggregation; the responses decreased after 1 min, however, when collagen was
      added prior to ACLA (Col + ACLA). Col + ACLA was 30% less effective than the ACLA
      + Col in: (1) the phosphorylation of pleckstrin and myosin light chain; and (2)
      the secretion of alpha- and dense granules. Indomethacin inhibited Ca2+
      mobilization, pleckstrin phosphorylation and cell aggregation in platelets
      stimulated by ACLA + Col. The thromboxane B2 level in platelets induced by ACLA +
      Col was similar to that stimulated by low concentrations of collagen alone. ACLA
      + Col increased the activities of phospholipase C (PLC) as determined by
      formation of phosphatidic acid (PA), whereas indomethacin and adenosine 2',5'
      diphosphate, an antagonist of the ADP P2Y1 receptor, inhibited PA formation.
      These results suggest that ACLA, thromboxane A2 derived from the collagen pathway
      and secreted ADP co-operatively augment PLC activity and lead to platelet
      aggregation.

PMID- 12199801
TI  - X-linked thrombocytopenia in a girl.
AB  - We report X-linked thrombocytopenia (XLT) in a 6-year-old girl with petechiae and
      thrombocytopenia from the age of 3 months. Her 2-year-old brother was also
      diagnosed with XLT. The Wiskott-Aldrich syndrome protein (WASP) gene was detected
      as a replacement of +5th G to Aon intron 6 using sequence analysis, and the WASP
      expression levels in this patient were one-third those of a healthy control. The
      X-inactivation analysis of the patients lymphocytes showed a random pattern of X
      chromosome inactivation. To our knowledge, this is the first confirmed report of
      XLT in a female.

PMID- 12199802
TI  - Detection of lupus anticoagulant identifies patients with autoimmune haemolytic
      anaemia at increased risk for venous thromboembolism.
AB  - Venous thromboembolism (VTE) is a well-recognized complication of autoimmune
      haemolytic anaemia (AIHA), and is a major cause of morbidity and mortality in
      this disorder. However, the incidence, pathogenesis and risk-factors for VTE in
      AIHA remain poorly defined. Lupus anticoagulants (LA) and anticardiolipin (ACA)
      antibodies are autoantibodies directed against epitopes on prothrombin or beta2
      glycoprotein I (beta2-GPI). Both LA and ACA (together called antiphospholipid
      antibodies, APLA) are associated with VTE. We have prospectively studied the
      occurrence of VTE and APLA in 30 patients with AIHA. VTE was objectively
      documented in eight (27%) patients. APLA were detected in 19 (63%) patients with
      AIHA, of whom nine (30%) had a LA and 17 (57%) ACA. Seven patients had both LA
      and ACA. Among the eight patients with VTE, LA was detected in five (63%) and ACA
      in four (50%). There was a statistically significant association between presence
      of LA and occurrence of VTE (RR: 7.50, 95% CI: 1.25-45.2, P = 0.03). VTE is a
      frequent and life-threatening complication of AIHA. Detection of the lupus
      anticoagulant in patients with AIHA identifies individuals at significantly
      increased risk for VTE. Future studies should address the role of prophylactic
      anticoagulation in patients with AIHA.

PMID- 12199803
TI  - Gender-specific phenotypic expression and screening strategies in C282Y-linked
      haemochromatosis: a study of 9396 French people.
AB  - Most features of C282Y-linked haemochromatosis support the implementation of
      population screening of the disorder in Caucasians. However, the penetrance of
      C282Y homozygosity is poorly documented and the strategy for population screening
      remains debated. Nine thousand three hundred and ninety-six subjects (3367 men,
      aged 25-40 years, and 6029 women, aged 35-50 years), attending three Health
      Appraisal Centres, were genotyped and assessed with respect to clinical and
      biochemical signs of haemochromatosis. Discriminant, logistic regression and
      graphic analysis were used to predict homozygosity. Results were validated in 135
      homozygotes detected through other family and population studies. Fifty-four
      subjects (10 men and 44 women) were homozygous for C282Y. All men had abnormal
      iron status and most had mild clinical symptoms compatible with haemochromatosis.
      Identification of all homozygous men required a transferrin saturation (TS)
      threshold of 50% in the study group (90% specificity) and of 40% in the
      validation group. Homozygous women differed clinically from non-homozygotes for
      the presence of distal arthralgias only (18%vs 6%, P < 0.03). Thirteen (29%) were
      iron-deficient (serum ferritin < 13 micro g/l) and undetectable by biochemical
      tests. Although the population studied was not fully representative of the
      general population, our data strongly suggests that, in young men, large-scale
      screening for C282Y homozygosity is justified and can be achieved by using TS
      prescreening. However, in premenopausal women, large-scale screening remains to
      be justified with respect to the natural history of haemochromatosis and should
      be directly genotypic.

PMID- 12199804
TI  - Mutation spectrum in Australian pedigrees with hereditary hyperferritinaemia
      cataract syndrome reveals novel and de novo mutations.
AB  - Hereditary hyperferritinaemia-cataract syndrome (HHCS) (OMIM #600886) is a rare
      autosomal dominant condition identified by high serum ferritin levels with normal
      iron saturation and distinctive bilateral cataract. It may be misdiagnosed as
      haemochromatosis and such patients become anaemic as a result of inappropriate
      venesection. The elevated serum ferritin is due to a mutation in the iron
      responsive element (IRE) of the l-ferritin gene, resulting in excessive l
      ferritin production. We report the identification of three Australian pedigrees;
      one with a previously described mutation at position 40, a pedigree with a novel
      mutation at position 39 and an individual with a de novo mutation at position 32
      of the l-ferritin IRE.

PMID- 12199805
TI  - Treatment of life-threatening post-haemorrhagic anaemia with cell-free
      haemoglobin solution in an adolescent Jehovah's Witness.
AB  - Severe blood loss carries an increased risk of a fatal outcome in patients who do
      not consent to the use of blood products. For patients who base this decision on
      a religious belief system, such as the Jehovah's Witnesses, important
      distinctions may exist between the appropriateness of various blood products. We
      describe the first successful use of purified human cell-free haemoglobin
      solution in a paediatric patient, in this case in the management of life
      threatening anaemia in a 14-year-old female Jehovah's Witness with immune
      thrombocytopenia.

PMID- 12199806
TI  - Life-threatening human parvovirus B19 infection transmitted by intravenous immune
      globulin.
AB  - Infection of human parvovirus B19 (B19) is usually a self-limiting febrile
      illness, but can sometimes be life-threatening under certain circumstances, such
      as aplastic crisis in patients with haemolytic anaemia, hydrops fetalis in
      pregnant women and fulminant hepatitis. B19 can be transmitted through
      respiratory secretions, transplacentally and by transfusion of blood or blood
      products. In the present case, administration of intravenous immune globulin
      (i.v.Ig) transmitted B19 infection and consequently caused pure red cell aplasia
      and aggravation of hepatitis to fulminant hepatitis. Our case may raise important
      questions as to the safety of i.v.Ig and possible contamination by B19.

PMID- 12199807
TI  - Is there a relationship between in vitro drug resistance and level of minimal
      residual disease as detected by polymerase chain reaction at the end of induction
      therapy in childhood acute lymphoblastic leukaemia?

PMID- 12199808
TI  - Successful response to rituximab in a patient with pure red cell aplasia
      complicating chronic lymphocytic leukaemia.

PMID- 12199809
TI  - Long-term remissions with weekly chlorambucil therapy in patients with
      intermediate-risk chronic lymphocytic leukaemia.

PMID- 12199812
TI  - Diagnosis and management of multiple myeloma.

PMID- 12199810
TI  - Relative erythrocytosis.

PMID- 12199814
TI  - Constitutional pericentric inversion of chromosome 9 and haemopoietic stem cell
      transplantation: delayed engraftment.

PMID- 12199815
TI  - Change in serum procalcitonin (deltaPCT) predicts the clinical outcome of
      children admitted with febrile neutropenia.

PMID- 12199816
TI  - Helicobacter pylori infection and idiopathic thrombocytopenic purpura.

PMID- 12199817
TI  - Kilt syndrome?

PMID- 12199820
TI  - Are the adverse consequences of cannabis use age-dependent?

PMID- 12199821
TI  - Addiction treatment in the United States: early pioneers and institutions.

PMID- 12199822
TI  - Have we lost our way? The need for dynamic formulations of smoking relapse
      proneness.
AB  - Current smoking cessation treatments seem to differ from one another in the
      proportion of ex-smokers who survive the first few days of the quit attempt.
      After this initial effect, parallel relapse processes appear to unfold in all
      treatment groups; no available treatments seem to alter the nature of this late
      relapse process. True relapse prevention will require that we obtain a better
      understanding of the forces contributing to relapse across the span of the
      cessation attempt. A working model of dynamic relapse processes may be necessary
      before treatments can be improved. In this paper, we suggest that the conceptual
      model of relapse proneness (RP) described originally by the National Working
      Conference on Smoking Relapse can serve as an ecumenical organizational framework
      that may be used to integrate and conceptualize relapse data in ways that could
      generate new strategies for relapse research and inform treatment design. As an
      illustration, we sketch a preliminary model of RP which postulates that physical
      withdrawal, stressors/temptations, and cessation fatigue each make independent,
      time-shifted contributions to relapse risk. A new round of descriptive research
      focused on relapse proneness processes may be a prerequisite for improving
      existing smoking cessation interventions.

PMID- 12199824
TI  - Substance abuse and compromise of fathering.

PMID- 12199823
TI  - Substance abuse and fathering: adding poppa to the research agenda.
AB  - Although a number of socioeconomic forces have converged across cultures to make
      fathering one of the more prominent social issues of the new millennium, the
      status of substance-abusing men as fathers is rarely acknowledged in the
      conceptualization of public policy, service delivery or research focusing on the
      adverse consequences of drug and alcohol abuse. In this commentary, the authors
      call for the substance abuse research community to expand understanding of
      fathering occurring across cultures in the context of chronic substance abuse.
      Building upon research being undertaken with other populations of fathers, the
      authors argue there is need to clarify (a) the number of substance-abusing
      fathers, (b) patterns of reproduction among substance-abusing men, (c) ways in
      which substance abuse contributes to compromise of fathering, (d) ways in which
      compromise of fathering contributes to psychological distress in substance
      abusing men, (e) ways in which compromise of fathering affects developmental
      outcomes for children, and (f) ways in which clinical and preventive intervention
      might be used to minimize the harm associated with paternal substance abuse.

PMID- 12199825
TI  - Substance-abusing fathers: descriptive, process and methodological perspectives.

PMID- 12199826
TI  - Finding poppa in substance abuse research.

PMID- 12199828
TI  - Cannabis use and psychosocial adjustment in adolescence and young adulthood.
AB  - AIM: To examine the associations between frequency of cannabis use and
      psychosocial outcomes in adolescence/young adulthood. DESIGN: A 21-year
      longitudinal study of the health, development and adjustment of a birth cohort of
      1265 New Zealand children. MEASUREMENTS: Annual assessments of the frequency of
      cannabis use were obtained for the period from age 14-21 years, together with
      measures of psychosocial outcomes including property/violent crime, depression,
      suicidal ideation, suicide attempt and other illicit drug use. FINDINGS: The
      frequency of cannabis use was associated significantly with all outcomes, and
      particularly other illicit drug use. Statistical control for confounding by both
      fixed and time-dynamic factors substantially reduced the strength of association
      between cannabis use and outcome measures. Nevertheless, cannabis use remained
      significantly (P < 0.05) associated with all outcomes and particularly other
      illicit drug use, after adjustment for confounding. For the measures of crime,
      suicidal behaviours and other illicit drug use there was evidence of age related
      variation in the strength of association with cannabis use, with younger (14-15
      years old) users being more affected by regular cannabis use than older (20-21
      years old) regular users. However, the association between cannabis use and
      depression did not vary with age. CONCLUSIONS: Cannabis use, and particularly
      regular or heavy use, was associated with increased rates of a range of
      adjustment problems in adolescence/ young adulthood-other illicit drug use,
      crime, depression and suicidal behaviours-with these adverse effects being most
      evident for school-aged regular users. The findings reinforce public health
      concerns about minimizing the use of cannabis among school-aged populations.

PMID- 12199830
TI  - The social cost of illegal drug consumption in Spain.
AB  - AIMS: The objective of this study was to estimate the social cost of the
      consumption of illegal drugs in Spain. DESIGN: We performed a cost-of-illness
      study, using a prevalence approximation and a societal perspective. The
      estimation of costs and consequences referred to 1997. As direct costs we
      included health-care costs, prevention, continuing education, research,
      administrative costs, non-governmental organizations and crime-related costs. As
      indirect costs we included lost productivity associated with mortality and the
      hospitalization of patients. Estimation of intangible costs was not included.
      FINDINGS: The minimum cost of illegal drug consumption in Spain is 88,800 million
      pesetas (PTA) (467 million dollars). Seventy-seven per cent of the costs
      correspond to direct costs. Of those, crime-related costs represent 18%, while
      the largest part corresponds to the health-care costs (50% of direct costs). From
      the perspective of the health-care system, the minimum cost of illegal drug
      consumption is 44,000 million PTA (231 million dollars). The cost of illegal drug
      consumption represents 0.07% of the Spanish GDP. This gross figure compares with
      2250 million PTA (12.5 million dollars) invested in prevention programmes during
      the same year, and with 12,300 million PTA (68.3 million dollars) spent on
      specific programmes and resources for the drug addict population. CONCLUSIONS:
      Although there are limitations intrinsic in this type of study and the
      estimations obtained in the present analysis are likely to be an underestimate of
      the real cost of this condition, we estimate that illegal drug consumption costs
      the Spanish economy at least 0.2% of GDP.

PMID- 12199829
TI  - Does marijuana use have residual adverse effects on self-reported health
      measures, socio-demographics and quality of life? A monozygotic co-twin control
      study in men.
AB  - AIMS: To assess the effects of former heavy marijuana use on selected aspects of
      health. DESIGN: A monozygotic co-twin control design was used to compare the
      health of former heavy marijuana using male monozygotic twins to that of their co
      twins who never used marijuana significantly. SETTING: In-person survey and
      questionnaires. PARTICIPANTS: Fifty-six marijuana use discordant monozygotic twin
      pair members of the Vietnam Era Twin (VET) Registry. MEASUREMENTS: Current socio
      demographic characteristics; current nicotine and alcohol use; life-time nicotine
      and alcohol abuse/dependence; past 5-year physical and mental health services
      utilization; and health-related quality of life. FINDINGS: The mean number of
      days on which the marijuana user twin used marijuana in his life-time was 1085,
      while the non-marijuana user used marijuana a maximum of 5 days. Marijuana was
      last used a mean of 20 years previously. No significant differences were found
      between the former marijuana user twins and their siblings for current socio
      demographic characteristics; current nicotine or alcohol use; life-time nicotine
      or alcohol abuse/dependence; past 5-year out-patient or emergency room visits,
      hospitalizations or medication use for medical problems; past 5-year mental
      health out-patient use or hospitalizations; or health-related quality of life.
      CONCLUSIONS: Previous heavy marijuana use a mean of 20 years earlier by a group
      of men who reported no other significant illicit drug use does not appear to be
      associated with adverse socio-demographic, physical or mental health adverse
      effects. The conclusions of the study are limited by possible participation and
      recall biases, relatively small sample size and the absence of a physical health
      examination.

PMID- 12199831
TI  - Survey of doctors prescribing diamorphine (heroin) to opiate-dependent drug users
      in the United Kingdom.
AB  - AIM: To determine the scale and practice of diamorphine (heroin) prescribing for
      opiate dependence in the United Kingdom in 2000. DESIGN: Postal survey. SETTING:
      England, Scotland and Wales. PARTICIPANTS: One hundred and eleven of the 164
      doctors in the United Kingdom on the Home Office record as holding a licence to
      prescribe diamorphine (response rate 68%), and 59 of the 108 doctors in the
      United Kingdom eligible to hold a licence (working in drug clinics), but not
      doing so (response rate 54%). MEASUREMENTS: The characteristics of doctors (a)
      holding a licence and (b) currently prescribing; the number of opiate users
      receiving a prescription; current treatment delivery, clinical criteria for
      patient eligibility; and reasons for prescribing or not prescribing diamorphine.
      FINDINGS: Seventy of the 111 doctors actually held a licence. While the majority
      were consultant psychiatrists, five were general practitioners. Forty-six were
      currently prescribing to 448 patients. The majority of prescribers reported that
      they had not initiated a prescription for diamorphine but had inherited patients
      already receiving such a prescription. Most of those who prescribed considered
      that in selected cases it could produce clinical and social improvement. There
      were great variations in clinical criteria for patient eligibility, prescribing
      practice, daily dose prescribed (range 5-1500 mg) and the daily dose-equivalent
      of 100 mg methadone (range 50-900 mg). Many respondents cited lack of appropriate
      resources as a reason for not prescribing to more patients. Reasons for non
      prescribing varied from lack of resources to little evidence of its
      effectiveness. CONCLUSIONS: The prescribing of diamorphine to opiate dependent
      drug users remains rare in the United Kingdom. Not all eligible doctors seek a
      licence to prescribe, and not all those with licences actually prescribe it.
      There is no clear consensus on who should be treated with diamorphine and in what
      way.

PMID- 12199832
TI  - Cigarette smoking and attention to signals of reward and threat in the Stroop
      paradigm.
AB  - AIMS: To test the prediction arising from the incentive-sensitization model of
      addiction that when tested immediately after smoking, smokers will show
      heightened attention to words with appetitive and aversive motivational
      significance compared with their performance during acute abstinence. DESIGN:
      Twenty-one smokers were each tested twice, once just after smoking and once after
      overnight abstinence, on three versions of the modified Stroop task which
      required colour naming of words with either neutral, appetitive or aversive
      connotations. Ten non-smokers were tested once. SETTING: All participants were
      tested in a quiet experimental cubicle within the psychology department.
      PARTICIPANTS: Smokers comprised nine men and 12 women who had smoked at least 10
      cigarettes per day for the last 6 months; non-smokers comprised five men and five
      women who had never smoked. All were aged between 18 and 35 years. Three smokers
      were excluded from the analyses because their breath CO levels suggested they had
      not complied with the instructions to abstain on one occasion. MEASUREMENTS: A
      card-based, blocked, format was used for the modified Stroop task. Time to colour
      name the words of the three motivational types, the order of which was
      counterbalanced across participants, was recorded. FINDINGS: Smoking was
      associated with greater interference from both threat and appetitive words than
      from neutral words; during abstinence there was no differential effect of word
      type. Non-smokers performed more similarly to recent smokers. CONCLUSIONS: This
      pattern suggests suppression of normal motivational responding during abstinence.

PMID- 12199833
TI  - Assessing 'stage of change' in current and former smokers.
AB  - AIMS: The concept of 'stage of change' is widely used by researchers and
      clinicians in the field of smoking cessation. Our aim was to assess the validity
      of three staging questionnaires and of the concept of 'stage of change' itself.
      SETTING AND PARTICIPANTS: Survey on the Internet in 1025 ever smokers, retest
      after 8 days in 318 people (31%), follow-up after 32 days in 451 people (44%).
      MEASUREMENTS: Three measures of 'stage of change'. FINDINGS: Participants (83
      93%) were classified in the same stage by all pairs of questionnaires, and 15%
      changed stage during an interval of 8 days. Including quit attempts in the
      'preparation' stage had a large impact on stage distributions, because 18-24% of
      smokers who had decided to quit in the next 30 days were downgraded to the
      'contemplation' stage as they had not made a quit attempt in the previous year.
      The 'action' stage included 5-7% of occasional smokers. Quit attempts during the
      past 7 days and 30 days were better predictors of smoking cessation than quit
      attempts during the past 12 months. Baseline stage and a continuous measure of
      intention predicted smoking abstinence at follow-up. CONCLUSIONS: These results
      reflect theoretical and methodological problems with the concept of stage of
      change. 'Stage' covers four different variables: current behaviour, quit
      attempts, intention to change and time since quitting. These variables are
      combined in a somewhat haphazard manner, none of them is measured
      comprehensively, and intention and time are continuous variables categorized by
      arbitrary cutpoints. Measuring each of these four variables independently may be
      preferable to using an incomplete mix of these elements.

PMID- 12199834
TI  - The Alcohol, Smoking and Substance Involvement Screening Test (ASSIST):
      development, reliability and feasibility.
AB  - AIMS: The Alcohol, Smoking and Substance Involvement Screening Test (ASSIST) was
      developed for the World Health Organization (WHO) by an international group of
      substance abuse researchers to detect psychoactive substance use and related
      problems in primary care patients. This report describes the new instrument as
      well as a study of its reliability and feasibility. SETTING: The study was
      conducted at participating sites in Australia, Brazil, Ireland, India, Israel,
      the Palestinian Territories, Puerto Rico, the United Kingdom and Zimbabwe. Sixty
      per cent of the sample was recruited from alcohol and drug abuse treatment
      facilities; the remainder was drawn from general medical settings and psychiatric
      facilities. METHODS: The study was concerned primarily with test item
      reliability, using a simple test-retest procedure to determine whether subjects
      would respond consistently to the same items when presented in an interview
      format on two different occasions. Qualitative and quantitative data were also
      collected to evaluate the feasibility of the screening items and rating format.
      PARTICIPANTS: A total of 236 volunteer participants completed test and retest
      interviews at nine collaborating sites. Slightly over half of the sample (53.6%)
      was male. The mean age of the sample was 34 years and they had completed, on
      average, 10 years of education. RESULTS: The average test-retest reliability
      coefficients (kappas) ranged from a high of 0.90 (consistency of reporting 'ever'
      use of substance) to a low of 0.58 (regretted what was done under influence of
      substance). The average kappas for substance classes ranged from 0.61 for
      sedatives to 0.78 for opioids. In general, the reliabilities were in the range of
      good to excellent, with the following items demonstrating the highest kappas
      across all drug classes: use in the last 3 months, preoccupied with drug use,
      concern expressed by others, troubled by problems related to drug use,
      intravenous drug use. Qualitative data collected at the end of the retest
      interview suggested that the questions were not difficult to answer and were
      consistent with patients' expectations for a health interview. The data were used
      to guide the selection of a smaller set of items that can serve as the basis for
      more extensive validation research. CONCLUSION: The ASSIST items are reliable and
      feasible to use as part of an international screening test. Further evaluation of
      the screening test should be conducted.

PMID- 12199835
TI  - South of the border: a legal haven for underage drinking.
AB  - AIMS: The research describes the characteristics and motivations of youthful San
      Diego County residents who patronize the bars and nightclubs in Tijuana, Mexico.
      DESIGN: Two random-digit-dial surveys of San Diego County residents-one group
      aged 18-20 years and one aged 21-30 years-was conducted during a 2-year period.
      Those who reported having visited the bars in Tijuana in the last year were
      compared with those who had not. SETTING: All respondents were residents of San
      Diego County, California, USA. PARTICIPANTS: The study comprised 2200 youths
      between 18 and 30 years of age. MEASUREMENTS: The interview protocol included
      questions covering demographic characteristics, drinking and drug-use history,
      experience with Tijuana bars, and ratings of bar features in San Diego and
      Tijuana. FINDINGS: About half of the 18-20-year-olds and a third of the 21-30
      year-olds reported visiting bars in Tijuana at least once in the past 12 months.
      Race, age, gender, heavy drinking and drug-use history were significantly
      associated with visits to Tijuana bars. The price of alcohol and the perceived
      freedom to get drunk in Tijuana bars were considered attractive features leading
      to cross-border drinking. CONCLUSIONS: The features of the alcohol service in
      Mexican bars that attract youthful drinkers (low cost and liberal availability of
      alcohol, lack of formal controls, and presence of heavy drinkers) are similar to
      those present in other drinking locales that lead to drunkenness. Thus, a better
      understanding of the characteristics and motivations of the US youths patronizing
      bars in Tijuana can lead to improved interventions to reduce heavy, risky
      drinking.

PMID- 12199836
TI  - Operation safe crossing: using science within a community intervention.
AB  - AIMS: To evaluate a large drunk-driving enforcement program at the US/Mexican
      border to reduce the number of youths crossing the border to drink in Tijuana.
      This paper also describes the research data used to develop and manage the
      program. Data from a border breath-test survey were used to dramatize the problem
      and gain public support for action. The data were also used to help design the
      enforcement effort and measure progress in reducing the cross-border drinking
      problem. DESIGN: The number of news events generated around the occurrence of
      special enforcement efforts were used to measure project activity and to predict
      changes in the numbers of youths crossing into Mexico, their returning BACs and
      reductions in alcohol-related crashes during a 3-year period. SETTING: An urban
      county on the Mexican border. PARTICIPANTS: Underage youths aged 18-20 years and
      young adults aged 21-30 years residing in San Diego County. MEASUREMENTS:
      Immigration and Naturalization Services provided population counts of the number
      of individuals crossing each weekend night from Tijuana into the United States
      through the San Ysidro border facility. Breath-test surveys of a random sample of
      these returning crossers provided data on the number of US residents visiting
      bars and nightclubs in Tijuana and on alcohol consumption at Tijuana bars and
      nightclubs. Night-time had-been-drinking crash data involving young drivers in
      several California counties served as an outcome measure of public health and
      safety. FINDINGS: Analysis of data involving more than 2 million pedestrians
      returning from Tijuana indicated that the Operation Safe Crossing program reduced
      the number of late-night crossers by 31.6%. CONCLUSIONS: Effective use of data
      through media advocacy programs to support an enforcement effort can reduce
      alcohol-related crashes.

PMID- 12199837
TI  - Amphetamine usage and genital self-mutilation.
AB  - Amphetamine usage has been associated with addiction, psychosis and self
      injurious behavior. We report on two patients who severely and repeatedly
      mutilated their own genitalia while intoxicated on amphetamines and consider
      possible diagnostic etiologies.

PMID- 12199839
TI  - Is extinction in animals the same as abstinence in humans?

PMID- 12199838
TI  - Cue-exposure treatment: time for change.

PMID- 12199840
TI  - A cluster of nine overdoses (one fatal) related to methadone in the north of
      France: a lesson for drug policy in frontier regions.

PMID- 12199846
TI  - Spain: youth, leisure, and alcohol consumption.

PMID- 12199847
TI  - Do multiple blood transfusions predispose for a higher rate of non-blood-related
      infection complications?
AB  - Allogeneic transfusions of red blood cell (RBC) concentrates have been related to
      an increase in postoperative infections. Leukocytes present in RBC units might
      have deleterious effects on the receptor immune system, provoking a state of
      immunosuppression that favors the development of postoperative infections (TRIM
      effect). The bioactive substances released by leukocytes in a time-dependent
      form, accumulating in blood components during storage, might be responsible for
      the TRIM effect. Multiple observational studies with logistic regression have
      demonstrated a direct relationship between transfusion and infection. However,
      several factors related to surgical difficulty and patient illness severity might
      act as strong confounding variables on the relationship studied. Randomized
      controlled trials designed to establish a causal relationship between transfusion
      and infection have yielded contradictory results. While we await new studies,
      allogeneic transfusions should be considered as a possible risk factor for
      postoperative infection.

PMID- 12199848
TI  - The status of antimicrobial resistance of Helicobacter pylori in eastern Europe.
AB  - OBJECTIVE: To evaluate the primary, secondary and combined resistance to five
      antimicrobial agents of 2340 Helicobacter pylori isolates from 19 centers in 10
      countries in eastern Europe. METHODS: Data were available for centers in
      Bulgaria, Croatia, the Czech Republic, Estonia, Greece, Lithuania, Poland,
      Russia, Slovenia and Turkey. Susceptibility was tested by agar dilution (seven
      countries), E test (five countries) and disk diffusion (three countries) methods.
      Resistance breakpoints (mg/L) were: metronidazole 8, clarithromycin 1,
      amoxicillin 0.5, tetracycline 4, and ciprofloxacin 1 or 4 in most centers.
      Primary and post-treatment resistance was assessed in 2003 and 337 isolates
      respectively. Results for 282 children and 201 adults were compared. RESULTS:
      Primary resistance rates since 1998 were: metronidazole 37.9%, clarithromycin
      9.5%, amoxicillin 0.9%, tetracycline 1.9%, ciprofloxacin 3.9%, and both
      metronidazole and clarithromycin 6.1%. Isolates from centers in Slovenia and
      Lithuania exhibited low resistance rates. Since 1998, amoxicillin resistance has
      been detected in the southeastern region. From 1996, metronidazole resistance
      increased significantly from 30.5% to 36.4%, while clarithromycin resistance
      increased slightly from 8.9% to 10.6%. In centers in Greece, Poland, and
      Bulgaria, the mean metronidazole resistance was slightly higher in adults than in
      children (39% versus 31.2%, P > 0.05); this trend was not found for
      clarithromycin or amoxicillin (P > 0.20). Post-treatment resistance rates
      exhibited wide variations. CONCLUSIONS: In eastern Europe, primary H. pylori
      resistance to metronidazole is considerable, and that to clarithromycin is
      similar to or slightly higher than that in western Europe. Resistance to
      amoxicillin, ciprofloxacin and tetracycline was detected in several centers.
      Primary and post-treatment resistance rates vary greatly between centers.

PMID- 12199849
TI  - Klebsiella typing: pulsed-field gel electrophoresis (PFGE) in comparison with O:K
      serotyping.
AB  - OBJECTIVE: To compare pulsed-field gel electrophoresis (PFGE) typing and O:K
      serotyping of Klebsiella in two different epidemiological settings. METHODS: One
      hundred and four bacteremia isolates without known epidemiological relation and
      47 isolates from an outbreak in a neonatal intensive care unit (NICU) were K
      typed by countercurrent immunoelectrophoresis (CCIE), O-typed by an inhibition
      enzyme-linked immunosorbent assay method, and typed by pulsed-field gel
      electrophoresis (PFGE) using the restriction enzyme XbaI. RESULTS: Typing data
      for the 104 bacteremia isolates were compared with regard to typability, number
      of types, maximum number of isolates per type, and the Discriminative Index (DI).
      O-typing combined with K-typing (DI 0.98) as O:K-serotyping (DI 0.99) gave a very
      discriminative typing system, whereas O-typing alone was not very discriminative
      (DI 0.76). PFGE (DI 1.00) was a more discriminative typing method than O:K
      serotyping, as it could subdivide 13/22 O:K-serotypes into smaller groups.
      Isolates with the same PFGE-type had the same O:K-serotype, indicating that
      isolates with different O- and/or K-types could be expected to be of different
      PFGE-types. Typing of the 47 isolates from the outbreak in the NICU showed that
      38 isolates belonged to a single clone, and that during an epidemic limited in
      time and space, differences in the electrophoretic patterns of up to five bands
      between a parental pattern type and a subtype may be found in the PFGE profiles.
      CONCLUSIONS: Both O:K-serotyping and PFGE typing are highly discriminative typing
      methods. PFGE is the most discriminative method and is excellent for typing
      outbreaks with few isolates. If large numbers of isolates are to be typed, a more
      convenient strategy might be first to K- or O:K-serotype isolates followed by
      PFGE typing of possible identical isolates. Since K- or O:K-serotyping is a
      definitive typing method, while PFGE typing is a comparative one, PFGE cannot,
      for the time being, replace O:K-serotyping for surveillance purposes.

PMID- 12199850
TI  - Candidemia in French hospitals: incidence rates and characteristics.
AB  - OBJECTIVE: To determine the incidence of candidemia in French hospitals.
      MATERIALS AND METHODS: A representative sample of 25 French hospitals [nine
      teaching hospitals (TH), ten general hospitals (GH) and six cancer referral
      centers (CRC)] was randomly selected. The incidence rates of candidemia per
      number of admissions and per patient-days of hospitalization were determined and
      extrapolated to the national level. RESULTS: From January 1, 1995 to December 31,
      1995, the overall incidence rate per 1000 admissions was 0.29, ranging from
      0.71/1000 in CRC, to 0.17/1000 in GH. The overall incidence for 1000 patient-days
      was 0.035 and the highest incidence was also observed in CRC (0.116/1000),
      followed by TH (0.052/1000). Candida albicans (53%) was the most common species
      isolated, a central venous catheter (26%) was the most common portal of entry and
      50% of the candidaemic patients had a neoplasm. CONCLUSION: This study should
      enable us to optimize surveillance, prevention and treatment of these potentially
      life-threatening infections.

PMID- 12199851
TI  - Detection of toxin production in Clostridium difficile strains by three different
      methods.
AB  - OBJECTIVE: To compare two immunoassays for detection of toxins produced in vitro
      by isolates of Clostridium difficile with the standard tissue culture assay, to
      help in the diagnosis of C. difficile-associated diarrhoea. METHODS: Toxin
      production was investigated in 42 strains of C. difficile of various serotypes,
      ribotypes and S-protein types. These included strains from our laboratory
      collection, strains freshly isolated from stool specimens of patients suspected
      of suffering from C. difficile-associated disease or of carrying it
      asymptomatically, and one reference strain (NCTC 11223). Toxin was assayed by (i)
      a rapid slide immunoassay (C. difficile toxin A test, Clearview, Oxoid), (ii) an
      enzyme-linked microplate immunoassay (C. difficile toxin A/B test, Techlab), and
      (iii) a tissue culture assay. The rapid slide assay and the enzyme immunoassay
      were performed according to the manufacturers' recommendations. The tissue
      culture assay was performed using Vero cells. RESULTS: Thirty of the 42 strains
      (71%) were shown to be positive for toxin A by the slide immunoassay and 34 of
      the strains (81%) were found to be toxin A/B producers by the enzyme immunoassay.
      The same 34 strains that were positive in the enzyme immunoassay also produced
      toxin B (cytotoxin) in the tissue culture assay. The sensitivity, specificity,
      and positive and negative predictive values for the rapid slide immunoassay
      method were calculated to be 88.2%, 100.0%, 100.0% and 66.7%, respectively, when
      compared to tissue culture assay results as the reference method. These values
      for the enzyme immunoassay method were all 100.0%. In this study eight strains
      were found to be non-toxin-producing by all methods. It is possible that there
      were four strains that only produced toxin B (A- B+), and were missed by the
      rapid A-only assay. CONCLUSIONS: We can recommend the use of the Techlab A + B
      enzyme immunoassay for the detection of toxin production by C. difficile strains
      because of its high sensitivity and specificity, its ease of use, and its
      capability of detecting both A- and B-type toxins.

PMID- 12199853
TI  - Salmonella prosthetic joint septic arthritis.
AB  - We describe a case of Salmonella enteritidis infection of a prosthetic knee joint
      that was cured with ceftriaxone therapy for 6 weeks and replacement of the tibial
      component of the prosthesis. Eleven other cases of salmonella prosthetic joint
      infection have been reported in the English-language literature. Five infections
      occurred within 20 days of prosthesis placement, and seven occurred several
      months to years later; ten of 12 infections involved hip prostheses. Nine of 12
      patients who had prosthesis removal were cured of the infection. Two of the three
      patients with retention of the prosthesis required long-term suppressive
      antibiotic therapy.

PMID- 12199852
TI  - Molecular epidemiology of predominant clones and sporadic strains of methicillin
      resistant Staphylococcus aureus in Switzerland and comparison with European
      epidemic clones.
AB  - OBJECTIVE: To assess the molecular epidemiology and risk factors of predominant
      clones and sporadic strains of methicillin-resistant Staphylococcus aureus (MRSA)
      in Swiss hospitals and to compare them with European strains of epidemic clones.
      MATERIAL AND METHODS: One-year national survey of MRSA cases. Analysis of
      epidemiological and molecular typing data (PFGE) of MRSA strains. RESULTS: In
      1997, 385 cases of MRSA were recorded in the five Swiss university hospitals and
      in 47 community hospitals. Half of the cases were found in Geneva hospitals where
      MRSA was already known to be endemic. Molecular typing of 288 isolates (one per
      case) showed that 186 (65%) belong to four predominant clones, three of which
      were mostly present in Geneva hospitals. In contrast, the fourth clone (85 cases)
      was found in 23 hospitals (in one to 16 cases per hospital). The remaining 35% of
      the strains were clustered into 62 pulsed field gel electrophoresis types. They
      accounted for one to five patients per hospital and were defined as sporadic.
      Multivariate analysis revealed no independent risk factors for harboring a
      predominant versus a sporadic strain, except that transfer from a foreign
      hospital increases the risk of harboring a sporadic strain (OR, 42; 95% CI, 5
      360). CONCLUSION: While cases with predominant clones were due to the local
      spread of these clones, most sporadic cases appear to be due to the continuous
      introduction of new strains into the country. With the exception of a transfer
      from a hospital outside Switzerland, no difference in the clinical or
      epidemiological characteristics was observed between patients harboring a
      predominant clone and those with a sporadic strain.

PMID- 12199854
TI  - Cytomegalovirus DNA concentration in plasma predicts development of
      cytomegalovirus disease in kidney transplant recipients.
AB  - The clinical significance of cytomegalovirus (CMV) DNA detection in post-kidney
      transplantation infection surveillance was examined by comparing the performance
      of three assays for detection of CMV in blood: the test for CMV-pp65-antigen in
      leukocytes, which is routinely employed in our laboratory, the quantitative
      plasma CMV-DNA-polymerase chain reaction (PCR; Cobas Amplicor CMV Monitor test)
      and the qualitative plasma CMV-DNA-PCR (Amplicor CMV test). Thirteen kidney
      transplant recipients were monitored with serial samples taken over a period of 3
      months following transplantation. The quantitative CMV-PCR was the test with
      highest sensitivity, 95.9%, vs. 88.9% and 76.9% for the CMV-pp65 antigen assay
      and qualitative CMV-PCR, respectively. The virus load in the first positive
      specimens, assessed as DNA-copies/mL, was significantly associated with CMV
      disease because five of the six patients who developed disease, but only one of
      the seven who did not develop disease, had more than 3000 CMV-DNA-copies/mL. The
      number of CMV-pp65 antigen-positive cells in the first positive specimens did not
      have predictive value for development of CMV disease. Assessment of CMV in plasma
      by the quantitative CMV-PCR is especially useful since it has a high sensitivity
      and the amount of CMV DNA in plasma is a good predictor of CMV disease.

PMID- 12199855
TI  - Clinical microbiological case: chronic disseminated candidiasis unresponsive to
      treatment.

PMID- 12199856
TI  - Clinical microbiological case: fever and headache in a heavy consumer of
      eucalyptus extract.

PMID- 12199857
TI  - Effect of antioxidants on the immune response of Helicobacter pylori.
AB  - Antioxidants are substances capable of inhibiting oxidation. In chronic diseases,
      inflammatory response cells produce oxygen free radicals. Oxygen free radicals
      cause DNA damage, and this may lead to gene modifications that might be
      carcinogenic. Chronic Helicobacter pylori infection causes the production of DNA
      damaging free radicals. In recent years, various groups have studied the effects
      of antioxidants, especially on H. pylori-associated gastric cancer. In most of
      the studies, it has been shown that H. pylori infection does affect the level of
      antioxidants measured in the gastric juice, but there are also controversial
      results. Recent experimental studies, both in vivo and in vitro, have shown that
      vitamin C and astaxanthin, a carotenoid, are not only free radical scavengers but
      also show antimicrobial activity against H. pylori. It has been shown that
      astaxanthin changes the immune response to H. pylori by shifting the Th1 response
      towards a Th2 T-cell response. Very few experimental studies support the
      epidemiologic studies, and further studies are needed to describe the effect and
      the mechanism of antioxidants in the H. pylori immune response.

PMID- 12199861
TI  - Physiological aspects of xenotransplantation, 2001.

PMID- 12199862
TI  - Transgenic perspectives in xenotransplantation, 2001.

PMID- 12199863
TI  - Extracorporeal liver perfusion as hepatic assist in acute liver failure: a review
      of world experience.
AB  - BACKGROUND: There are almost no prospective, controlled and randomized clinical
      trials comparing different approaches towards hepatic assist. In order to create
      a basis for comparing the value of the existing different hepatic assist methods
      this article offers a systematic review of the world experience with allogeneic
      or xenogeneic extracorporeal liver perfusion (ECLP). METHODS: An Internet
      assisted search was conducted in the international literature published from 1964
      to 2000. Only articles with a clear description of methodology and outcome of
      patients were included. For multivariate analysis of variance the general linear
      method (GLM) procedure was used. Differences within the groups were analyzed by
      chi-square test. Data of 198 patients were included into the statistical analysis
      for systematic review. RESULTS: The long-term survival rate (SVR) of these
      patients was 26%, thus not exceeding published data concerning SVR under standard
      intensive care. Age below 40 years (P<0.029), coma stage lower than III-IV
      (P<0.003), total perfusion time over 10 hours (P<0.024), hepatitis B as cause for
      acute liver failure (ALF) (P<0.05) as well as use of baboon and human livers
      (P<0.02) were identified as independent positive prognostic markers for improved
      survival. ECLP as bridging therapy to liver transplantation was successful in 12
      of 14 patients. CONCLUSION: ECLP using pig livers did not surpass the success of
      conventional intensive care treatment. An additional effect of transgenic
      expression of human regulators of complement regulation in porcine livers has not
      yet been proven. ECLP with human livers not suitable for liver transplantation
      might prove effective and practicable for temporary hepatic support. Bridging to
      liver transplantation by long-term ECLP using porcine and human livers appears to
      have comparable efficacy as bioartificial support methods.

PMID- 12199864
TI  - Xenogeneic human NK cytotoxicity against porcine endothelial cells is
      perforin/granzyme B dependent and not inhibited by Bcl-2 overexpression.
AB  - Because of organ shortages in clinical allotransplantation, the potential of pig
      to-human xenotransplantation is currently being explored showing a possible
      critical role for natural killer (NK) cells in the immune response against
      xenografts. Therefore, we analyzed the cytotoxic pathways utilized by human
      natural killer cells (hNK) against porcine endothelial cells (pEC). Transmission
      electron microscopy of pEC cocultured with hNK cells showed both apoptotic and
      necrotic cell death, whereas soluble factors such as Fas ligand or TNFalpha did
      not induce apoptosis in pEC. NK lysis of pEC was abrogated by concanamycin A and
      ammonium chloride, reagents inhibiting the perforin/granzyme B (grB) pathway, but
      only partially blocked by caspase inhibition with z-VAD-fmk. Overexpression of
      bcl-2 protected pEC against apoptosis induced by staurosporine or actinomycin D,
      but failed to prevent hNK cell-mediated lysis. In conclusion, pEC are lysed in
      vitro by hNK cells via the perforin/grB pathway and are not protected from NK
      lysis by overexpression of bcl-2.

PMID- 12199865
TI  - Characterization of baboon anti-porcine IgG antibodies during acute vascular
      rejection of porcine kidney xenograft.
AB  - In the pig-to-baboon model, the removal of anti-porcine natural antibodies
      abrogates hyperacute vascular rejection (HAVR), but the xenograft then undergoes
      an acute vascular rejection (AVR) concomitantly to the appearance of newly formed
      anti-porcine antibodies. The use of anti-IgM monoclonal antibody (mAb) in baboons
      allowed to avoid HAVR of pig-to-baboon renal xenografts, but, at post-operative
      day 6, AVR occurred because of a rapid return of anti-porcine antibodies. The aim
      of this work was to characterize the anti-porcine antibodies during AVR. Sera
      from anti-IgM-treated animals were assessed prior to the graft and at the time of
      AVR by enzyme linked immunosorbent assay (ELISA) to determine anti-porcine
      antibodies concentration as well as the IgG subtypes. The same sera were tested
      on confluent cultures of porcine aortic endothelial cells (PAECs) to assess (i)
      the cytolytic complement-dependent activity and (ii) the E-selectin expression.
      The K affinity of anti-Gal IgG antibodies was measured by ELISA. Anti-porcine
      (Gal and non-Gal) IgG antibodies were tested on PAECs by flow cytometry to
      discriminate the presence of Gal epitopes from the recognition of other porcine
      epitopes. We found that both anti-porcine IgM and IgG antibodies presented a
      significantly increased cytolytic activity and E-selectin expression on PAECs
      during AVR. These characteristics are related to an important increase of the
      antibody (Ab) titer (especially anti-galactosyl) and a switch to anti-galactosyl
      IgG1 subclass production, whereas the K affinity remained unchanged. The
      deleterious effects of both IgM and IgG antibodies observed during AVR showed the
      crucial need for treatment controlling the cells producing anti-porcine
      antibodies.

PMID- 12199866
TI  - Human serum-induced porcine endothelial cell E-selectin expression is associated
      with IgG3 and IgM anti-Gal antibodies.
AB  - Naturally occurring anti-Galalpha1-3Gal (anti-Gal) antibodies and complement
      induce hyperacute rejection (HAR) of porcine organs transplanted to primates. If
      the hyperacute reaction is prevented, an acute vascular rejection (AVR) occurs
      within hours to few days. Antibodies are important for the development of AVR,
      whereas the role of complement is still not clarified. AVR is characterized by
      protein synthesis-dependent endothelial cell (EC) activation. In the present
      study we investigated the relation between EC activation as measured by E
      selectin expression, and the concentrations of anti-Gal antibodies of IgM, IgG
      and IgG subclasses in sera from 80 healthy blood donors selected on the basis of
      sex and age. There was a significant correlation between E-selectin expression
      and the concentration of IgG3 anti-Gal (r=0.39; P=0.019), which was not seen for
      the other IgG subclasses or for total IgG anti-Gal. A modest, but significant
      correlation was found between the concentration of IgM anti-Gal and E-selectin
      expression (r=0.38; P=0.040), but not between IgM and IgG3 anti-Gal. There was a
      large interindividual variation in anti-Gal antibodies, 50-fold for IgM and 70
      fold for IgG. Females had significantly higher concentrations of IgM anti-Gal
      than males (P=0.0006), which was explained by a substantial increase in IgM anti
      Gal concentration in younger women. The concentration of IgG anti-Gal and the
      degree of E-selectin expression did not differ between sex or age groups. In
      conclusion, the close correlation between anti-Gal antibodies of the potent
      complement activating IgG3 subclass and porcine EC activation, may imply that
      these antibodies play a role in EC activation characteristic of AVR.

PMID- 12199867
TI  - Results of crossmatch between chimpanzee lymphocytes and sera of highly
      sensitized potential renal transplant recipients.
AB  - BACKGROUND: We tested the hypothesis that patients with a high frequency of
      lymphocytotoxic antibodies against human cells are not highly sensitized to major
      histocompatibility complexes expressed by chimpanzee cells. METHODS: Sera from
      six "hopelessly" sensitized patients (percentage reactive antibodies (PRA) > 99%)
      on the renal transplant waiting list were crossmatched with peripheral blood
      lymphocytes from 10 chimpanzees. Lymphocytotoxic antibodies reacting with
      chimpanzee peripheral blood lymphocytes were identified. RESULTS: Three of the
      six patients with a high frequency of lymphocytotoxic antibodies against human
      cells had no xenospecific antibodies. CONCLUSION: Patients with a high frequency
      of lymphocytotoxic antibodies against human cells are not all panel-reactive to
      chimpanzees. Unilateral donor nephrectomy in non-human primates may offer an
      opportunity for safe expansion of the donor organ pool for these patients.

PMID- 12199868
TI  - Is exercise of value in the prevention of fragility fractures in men?
AB  - Exercise during growth seems to build a stronger skeleton resulting in a high
      peak bone mineral density (BMD) in men. Exercise during adulthood produces
      benefits in BMD or prevents bone loss, but the changes are of minor biological
      significance as regards fracture reduction. However, prospective intervention
      studies suggest exercise to improve muscle strength, co-ordination and balance,
      even in octogenarians--all traits possible to reduce the number of falls. It is
      virtually impossible to undertake a randomized blinded study of exercise with
      fracture as end point due to the large cohorts needed. Retrospective and
      prospective observational and case control studies suggest activity to be
      associated with reduced fracture risk. This may be correct, but consistently
      replicated sampling bias may produce the same observation. The Achilles heel of
      exercise is the cessation of physical activity. Biologically important benefits
      in BMD or improvement in muscle size and strength achieved by exercise during
      growth and young adulthood seem to be eroded in retirement, leaving virtually no
      remaining benefits in old age, the period when fragility fractures exponentially
      rise. On the contrary, continued exercise on a lower level may maintain some of
      the musculoskeletal benefit, but dose-response relationships need to quantified,
      as do the effects of exercise on bone size, shape, architecture and frequency of
      injurious falls. Absence of evidence is not evidence of absence of effect, but if
      we recommend exercise then should this be to children, adults, elderly men or men
      with fractures? What type of exercise? For how long? How many fewer fractures
      will result in the community from a community based exercise campaign like the
      anti-tobacco campaign? The higher level of proof, suggesting exercise to reduce
      spine and hip fractures must come from well designed and executed prospective
      randomized studies. Blinded studies obviously cannot be done but open trials can,
      and should be undertaken.

PMID- 12199869
TI  - Effects of montelukast on physical performance and exercise economy in adult
      asthmatics with exercise-induced bronchoconstriction.
AB  - Leukotriene antagonists are effective in the treatment of exercise-induced
      bronchoconstriction. Montelukast is a specific cysteinyl-leukotriene receptor1
      antagonist without known effects on the pulmonary vessels, which in theory should
      be advantageous with respect to gas exchange. In addition to lung function, we
      investigated the effects of montelukast on parameters of gas exchange and
      physical performance in 16 asthmatics with exercise-induced bronchoconstriction
      in a double-blind cross-over placebo-controlled study. Subjects were tested at an
      ambient temperature of -15 degrees C with a tread mill exercise protocol
      consisting of consecutive workloads of 80% V'O(2max) (6 min), rest (4 min), 60%
      V'O(2max) (6 min) and step increments of exercise until exhaustion. Montelukast
      reduced the maximum post-exercise fall in FEV1 (P < 0.01), improved the running
      time to exhaustion in 11 of 16 test subjects (one unchanged) (P = 0.03), and
      reduced the Borg score at exhaustion (P = 0.03) and the breathing frequency after
      3 min at 60% V'O(2max) (P = 0.03). V'(O2), V'CO(2), minute ventilation,
      ventilatory equivalents, respiratory exchange ratio, heart rate and oxygen pulse
      were not significantly different after montelukast and placebo. We conclude that
      montelukast has a beneficial effect on physical performance in most adults with
      exercise-induced asthma without any observed effect on gas-exchange parameters.

PMID- 12199870
TI  - Reliability of isokinetic supine bench press in healthy women using the Ariel
      Computerized Exercise System.
AB  - The aim of this study was to assess reliability of the Ariel Computerized
      Exercise System (ACES) "multifunction exerciser". Twenty-three healthy women
      completed three sets, three repetitions each, of maximal isokinetic supine bench
      press at two different velocities, slow (10/s) and moderate (25/s). The following
      performance parameters were studied: peak and average force, peak and average
      power, and total work. The experiment was repeated for two days. Intraclass
      correlation coefficients (ICC[2,1]) varied between 0.947 and 0.755 at 10
      degrees/s and between 0.861 and 0.654 at 25 degrees/s. The standard error of the
      measurement (SEM), the smallest detectable difference (SDD), and the coefficient
      of variation (CV) indicated that it is possible to achieve reliable and
      clinically relevant measurements with the ACES.

PMID- 12199871
TI  - Fluoroscopic validation of electrogoniometrically measured femorotibial
      translation in healthy and ACL deficient subjects.
AB  - Equipment which measure femorotibial motions indirectly by using a patellar pad
      are reported to have errors caused by deformation of soft tissues and slippage of
      the device. For the purpose of validation, the tibial translation in relation to
      the femur per degree of knee extension was estimated from the slope coefficients
      of the flexion-displacement curve, obtained by both fluoroscopic and
      electrogoniometric tests, in the knee of the dominant limb in healthy subjects
      and in both knees of patients with unilateral anterior cruciate ligament (ACL)
      deficiency. In addition, the anterior and posterior static knee laxity limits and
      the tibial resting position were evaluated. Within all knee groups, the tibia
      moved posteriorly in relation to the femur during extension. The measured
      movement was similar both with the electrogoniometer and with fluoroscopy thereby
      indicating that sagittal plane knee translation measurements with the CA-4000
      electrogoniometer are reliable and in good agreement with the X-ray measurements,
      even though the measurements were made separately. The ACL injured knees showed
      approximately 20% smaller posterior movement of tibia in relation to femur per
      degree change of knee extension than the non-injured or control knees (p < 0.05)
      and a more anterior resting position of the tibia relative to femur as compared
      to the contralateral healthy knee during knee laxity testing (p = 0.002).

PMID- 12199872
TI  - Self-reported hamstring injuries in student-dancers.
AB  - Dancing involves powerful movements as well as flexibility exercises, both of
      which may be related to specific injuries to the musculo-tendinosus tissue, e.g.,
      the hamstring muscle complex. In this study, the occurrence of acute and overuse
      injuries to the rear thigh in dancers was investigated retrospectively by means
      of a questionnaire. All but one (n = 98) of the student-dancers (age 17-25 years)
      at the Ballet Academy in Stockholm participated. The results demonstrated that,
      during the past 10 years, every third dancer (34%) reported that they had acute
      injuries and every sixth dancer (17%) had overuse injuries to the rear thigh.
      Most (91%) of the acute injuries were subjectively located to an area close to
      tuber ischiadicum. The majority (88%) stated that the acute injury occurred
      during slow activities in flexibility training, e.g., splits, and only a few
      (12%) in powerful movements. Continuing problems were reported by 70% of the
      acutely injured dancers. Many of the dancers neglected their acute injury (14 did
      not even stop the ongoing dance activity) and they also greatly underestimated
      the recovery time. Only 4 dancers (12%) received acute medical assistance. Thus
      the results, based on the recollection of the subjects, indicated that stretching
      could induce severe strain injuries to the proximal hamstrings in dancers.
      Extrapolating these results to the practice, it can be recommended that
      stretching exercises be executed with caution in connection with dancing sessions
      and training, and that, information about the seriousness and acute treatment of
      such injuries be added to the student-dancers' curriculum.

PMID- 12199873
TI  - Fracture-dislocation of the tarsal navicular in a soccer player.
AB  - We describe an unusual injury of the mid-tarsal region in a soccer goalkeeper.
      The injury occurred in a training game as a result of an abduction-plantar
      flexion. Radiographs showed a fracture-dislocation of the tarsal navicular. The
      patient was treated by closed reduction with percutaneous fixation using two
      Kirschner wires. The end-result was satisfactory but the patient felt pain in the
      mid-foot during and after sports activities and was unable to continue playing as
      a goalkeeper.

PMID- 12199874
TI  - The relationships between physical activity, health status and psychological well
      being of fertility-aged women.
AB  - The purpose of this investigation was to measure the association between leisure
      time physical activity and health status, mental health and depression. The
      participants were women aged 18-45. The data were collected using questionnaires
      that were mailed to 1200 women. The response rate was 55%. The questionnaire
      contained three instruments: the General Health Questionnaire (GHQ), the Health
      Questionnaire for Adults, and the Beck Depression Inventory (BDI). The results
      showed that 52.8% of the sample were physically inactive. Physically active women
      experienced better mental health (P < 0.05), less depression (P < 0.05) and they
      had better general health status (P < 0.005). Differences in the emotional state
      (GHQ score) and depression (BDI score) between active (participating in exercise
      3 or 1-2 times a week) and inactive women were significant (P < 0.05). Even a low
      level of physical activity (1-2 times per week) was positively related to women's
      mental health (P < 0.05).

PMID- 12199875
TI  - Eating disorder behavior in physically active Norwegian women.
AB  - Competitive female athletes may have higher risk of eating disorders (ED) than
      recreational athletes, in part because low body fat may be advantageous in
      sports. However, women who participate in sports or physical activities might
      also do this for weight reduction, altering body shape, and for other food
      related reasons. This study was conducted to evaluate the association between
      hours of leisure time physical activity (PA) and prevalence of ED, and whether
      the association between the Eating Disorders Inventory (EDI) scales and ED, as
      classified by the Survey of Eating Disorders (SED), was the same among women with
      high vs. low physical activity levels. The community-based study sample consisted
      of 898 female students aged 18-50 years. Subjects filled out the EDI, the SED,
      and a questionnaire concerning physical activity and demographic data. Physical
      activity was not associated with increased risk of having a SED-defined diagnosis
      of an ED or of having an EDI score greater than 40, which is sometimes used to
      define women at risk for having an eating disorder. Women with a SED-defined ED
      had higher scores on all subscales of the EDI, but did not differ with respect to
      age, BMI or hours of weekly activity. The strongest predictors of having a SED
      defined ED were body mass index (BMI), two EDI scales, drive of thinness and
      Bulimia Nervosa, with no differences between the two PA groups. Among women with
      a SED-defined ED, those with more than 5 h weekly PA did not differ from others
      with respect to scoring on the EDI or BMI. Results suggest that hours of physical
      activity may not increase risk of developing ED. Effective interventions are
      needed to help the growing numbers of persons with body-image and eating
      difficulties. For some, moderate physical training might be helpful.

PMID- 12199877
TI  - Evidence-based nursing: a defence.

PMID- 12199878
TI  - Methodological strategies for the identification and synthesis of 'evidence' to
      support decision-making in relation to complex healthcare systems and practices.
AB  - This paper addresses the limitations of current methods supporting 'evidence
      based health-care' in relation to complex aspects of care, including those
      questions that are best supported by descriptive or non-empirical evidence. The
      paper identifies some new methods, which may be useful in aiding the synthesis of
      data in these areas. The methods detailed are broadly divided into those that
      facilitate the identification of evidence and those that enable the
      interpretation of the data retrieved. To illustrate some of the issues involved,
      reference is made to a multimethod review recently completed by the authors,
      which aimed to identify factors that promote continuity in the transition from
      child to adult health and social care. It is argued that as healthcare
      organisations are becoming increasingly preoccupied with the evidence base of
      practice, such methods may help ensure that aspects of care and approaches that
      are outside the dominant pharmaco-medical domain maintain a prominent position on
      the healthcare agenda while remaining open to external scrutiny. Healthcare
      professionals who use such approaches need to know their relative utility and
      benefits to inform clinical decisions, so as to ensure that best practice is
      observed.

PMID- 12199879
TI  - Governing nursing conduct: the rise of evidence-based practice.
AB  - Drawing on the Foucauldian concept of 'governmentality' to analyse the evidence
      based movement in nursing, we argue that it is possible to identify the
      governance of nursing practice and hence nurses across two distinct axes; that of
      the political (governance through political and economic means) and the personal
      (governance of the self through the cultivation of the practices required by
      nurses to put evidence into practice). The evaluation of nursing work through
      evidence-based reviews provides detailed information that may enable governments
      to target and instruct nurses regarding their work in the interest of preserving
      the health of the population as a whole. Political governance of the nursing
      population becomes possible through centralised discursive mechanisms, such as
      evidence-based reviews that present nursing practice as an intelligible field
      whose elements are connected in a more or less systematic manner. The identity of
      the evidence-based nurse requires the modern nurse to develop new skills and
      attitudes. Evidence-based nursing is an emerging technology of government that
      judges nursing research and knowledge and has the capacity to direct nursing
      practice at both the political and personal level.

PMID- 12199880
TI  - The oil crisis, risk and evidence-based practice.
AB  - Evidence-based practice has risen to prominence over the last 20 years. Different
      professions have taken it up in different ways and for different purposes. It has
      been seen as holding both threats and advantages to professionalising endeavours
      and professional identity. It has engendered controversy but some criticisms of
      it have been unconvincing. It is possible to account for its rise as a response
      to tightening financial constraints on state spending in the west, as a sign of a
      culture increasingly concerned with risk, distrust of professionals and experts,
      as well as a way for professionals themselves to maintain control over their
      activity in the face of growing managerialism. This paper reviews the literature
      of some of the movement's proponents as well as criticism from various
      professional groups. It concludes that more useful than either arguing for or
      against it, is to understand the policy background and sociological reasons for
      its emergence and spread.

PMID- 12199881
TI  - Transformative unlearning: safety, discernment and communities of learning.
AB  - This paper aims to stimulate awareness about the intellectual and emotional work
      of 'unlearning' in knowledge workers in the emerging learning age. The importance
      of providing a safe space for dialogue to promote transformative learning,
      through building 'communities of learning', is highlighted. Unlearning is
      conceptualized within a transformative education paradigm, one whose primary
      orientation is discernment, a personal growth process involving the activities of
      receptivity, recognition and grieving. The author utilizes the metaphor of an
      unfolding spiral path to explore her experience of needing to 'unlearn' a trusted
      nursing practice prior to 'learning' new best caring practices related to infant
      sleep positions. Macro and micro approaches to facilitating unlearning in
      organizations, in learners and in nurses are suggested.

PMID- 12199882
TI  - Recognising relationships: reflections on evidence-based practice.
AB  - This paper argues for a broadening of the way evidence is developed and used in
      health-care. It contends that the current political and policy imperatives and
      the evidence-based practice movement are in direct tension with the other major
      ideological movements that promote patient-centred healthcare services. Nursing
      is affected by this tension because it is more naturally focused on relationships
      with clients to achieve health outcomes. The unresolved and mounting tension
      could be alleviated by embracing a broader definition of what counts as evidence
      and by focusing more on patient-centred healthcare methodologies and
      acknowledging the interdependency of distinct ways of generating new knowledge. A
      number of case studies are used to illustrate how research focusing on patient
      perspectives and nurses' response to patient experiences can improve the evidence
      base for nursing.

PMID- 12199883
TI  - High technology and nursing: ethical dilemmas nurses and physicians face on high
      technology units in Norway.
AB  - Results from two studies of ethical dilemmas nurses and doctors experience on two
      high-technology units are compared and discussed. The qualitative comparative
      methodology of grounded theory was used to generate theoretical frameworks
      grounded in the empirical realities of the units. The ethical dilemmas they faced
      were related to: treating the one vs. the common good; end of life questions; and
      resource allocations with inadequate staffing. Similarities were related to
      intensity and urgency of nursing care and patient treatment, clear nursing
      ideologies based on treating humans within a framework of hope, embracing
      technology and scarce resources. Differences between the two study units were
      patient diagnosis, hierarchical structure on one unit while one had a vertical
      structure and decision-making processes, and finally how nursing knowledge and
      autonomy were used. The two studies demonstrated that clinical, ethical and
      administrative interactions and decisions are highly compounded, stressful and
      intertwined.

PMID- 12199884
TI  - Exploring nursing expertise: nurses talk nursing.
AB  - It has become increasingly important for practitioners to articulate their
      expertise in modern healthcare settings that demand high levels of accountability
      and evidence-based practice. The material presented within this article has been
      interpreted drawing from discourse analysis1 to help explore the discourses that
      shape and influence understandings of nursing practice. What we present are
      extracts from four of the 35 participant nurses who applied to take part in the
      Royal College of Nursing Institute's Expertise in Practice (pilot) Project (EPP).
      The material presented is used to provide a starting point for exploring how
      nurses talk about and construct expertise in nursing practice. The four nurse
      participants' clinical practice areas cover palliative care, mental health,
      intensive care and fertility care. The material reveals high levels of intensity
      in the nurse-patient relationship, 'maverick' nursing practices and ongoing
      reflexivity. All of these aspects appear to capitalize on expertise as a
      'catalyst' that alters treatment pathways and maximizes patient-centred outcomes.
      Exploring a discourse of nursing expertise exposes the tacit situated nature of
      professional practice that is heterogeneous and most difficult to articulate and
      explain. It is proposed that expertise tends to be understood from traditional
      and dominant discourses of medicine, management and technology. Explaining
      expertise in practice exposes non-conventional practice that in itself can be
      isolating and challenging to the status quo of contemporary health-care.

PMID- 12199885
TI  - Agonizing care: care ethics, agonistic feminism and a political theory of care.
AB  - 'Care' is central to nursing theory and practice, and has been described in a
      variety of ways. Intense conversations about care have been developing in other
      fields of study as well, from the social sciences to the humanities. Care ethics
      has grown out of intellectual exchange between feminist thought, moral theory and
      the critique of traditional western political philosophy. However, care ethics is
      not without its critics, as these accounts of care have also sparked vigorous
      challenges. This paper traces the construct of care through nursing theory, care
      ethics, feminist critiques of moral and political theory and agonistic feminism
      to outline a set of problematics that a political theory of care should engage.
      It discusses how care is conventionally posited in more or less essentialist,
      universalizing and naturalizing terms. It introduces the ideas of feminist
      theorists who resist dichotomizing care and the political, and situate care in
      the context of power and politics. The tensions between care feminism and
      agonistic feminism are highlighted in order to explore the potential of
      theorizing both care and nursing in political terms.

PMID- 12199886
TI  - Using text as data and writing as the method of inquiry and discovery.

PMID- 12199888
TI  - The British Society of Paediatric Dentistry: 50 years of achievement.
AB  - This paper describes the origins of organizations for children's dentists in the
      UK, starting 50 years ago and culminating in the foundation of the British
      Society of Paediatric Dentistry. It focuses on some of the people who were
      instrumental in these developments and their relations with children's dentists
      worldwide.

PMID- 12199889
TI  - Evidence for reversal of the caries decline among Norwegian children.
AB  - OBJECTIVE: The purpose of the present study was to report on caries status and to
      explore possible reasons for changes in caries experience among 5- and 12-year
      old Norwegian children. DESIGN: National cross-sectional and time trend study.
      METHODS: Aggregated data from the Public Dental Services and from official
      statistics were used. Information was available on the total number of children,
      the proportion receiving treatment, sale of fluoride tablets, socio-economic
      background, caries prevalence and dmft/DMFT scores. RESULTS: The prevalence of
      caries among 5-year-olds reached a low of 30.4% in 1997 and increased to 38.9% in
      2000. The mean dmft scores increased from 1.1 to 1.5. Conversely, the prevalence
      of caries among 12-year-olds decreased from 55.4% in 1997 to 52.2% in 2000 and
      the mean DMFT score from 1.7 to 1.5. Bivariate analyses at county level revealed
      significant associations, which for the most part disappeared in multivariate
      analyses. The sale of fluoride tablets had a significant effect on caries
      prevalence among 5-year-olds in 1998, in 1999 and in 2000. Infant mortality was
      associated with the dmft score in 1999. The only consistently significant
      predictor of caries experience at 12 years of age was caries prevalence at age 5.
      CONCLUSIONS: There has been a highly significant increase in caries experience
      among 5-year-olds (P < 0.001) and a levelling off among 12-year-olds over the
      past 3 years. Considering the association between caries prevalence at age 5 and
      caries experience at 12 years of age, there is a need for reassessment of the
      caries preventive programmes for children in Norway.

PMID- 12199890
TI  - Diagnostic features and pedodontic-orthodontic management in dentinogenesis
      imperfecta type II: a case report.
AB  - Dentinogenesis imperfecta type II, also known as hereditary opalescent dentin, is
      an isolated inherited condition transmitted as an autosomal dominant trait
      affecting the primary and permanent dentition. The combined pedodontic
      orthodontic management of a 4-year-old child is described. Following orthodontic
      analysis to encourage a favourable growth outcome, treatment comprised
      restoration of the primary teeth with stainless steel crowns and composite
      crowns. Differential diagnosis and alternative therapies, including orthodontic
      considerations, are discussed.

PMID- 12199891
TI  - Feeding and oral hygiene habits of preschool children in Hong Kong and their
      caregivers' dental knowledge and attitudes.
AB  - OBJECTIVES: This study was designed to gather data on infant feeding habits and
      oral hygiene practices of Hong Kong preschool children, on the dental knowledge
      and attitudes of their caregivers and on the oral health status of the same group
      of children. DESIGN: Cross-sectional study. SAMPLE AND METHODS: Data was gathered
      for a total of 369 boys and 297 girls (207 1-year-olds, 269 2-year-olds and 190 3
      year-olds) with a mean age of 20.19 (+/- 0.38) months. Information related to
      children attending six randomly selected Maternity and Child Health Centres. It
      was obtained by examining the children and by interviewing the attending
      caregivers and completing a questionnaire. Each child was given an oral
      examination using a torch, disposable mirror and wooden tongue spatula. RESULTS:
      Only 7% of the children were exclusively breast-fed. More than 98% (656/666) of
      infants used a nursing bottle for at least some drinks. Over 62% (411/656) had
      used a nursing bottle to take fluids other than water and infant formula. At
      bedtime, 56% (361/656) were given a nursing bottle prior to sleep and 96%
      (340/361) of these bottles contained formula milk. Of these children, only 37%
      (131/361) finished the contents of the bottle before falling asleep. Over 73%
      (139/190) of the children continued to use a feeding bottle after 2 years of age.
      Non-nutritive sucking habits were practised by 35.6% (237/666) of the children.
      Visible plaque, on the labial surface of at least two maxillary incisors, was
      found in 19.5% (120/615) of the children. Oral cleansing habits were practised
      for 66.2% (441/666) of the children. Toothbrushing habits were reported for 42.3%
      (260/615) of the dentate children, of whom 19% (49/260) had their teeth brushed
      twice daily. Toothpaste was used by 49.23% (128/260) of the children and 57.3%
      (149/260) brushed their own teeth. Caries was seen in 7.6% of the infants
      (47/615). Of the caregivers, 67.7% said they did not think carious primary teeth
      needed to be restored. Among the mothers, 12.6% (43/342) did not know the oral
      condition of their child. Reportedly, 82% (417/510) and 87.5% (446/510) of the
      mothers had not received any oral health care information during the ante- or
      postnatal periods. Nearly all, 97%, of the respondents said that they would like
      to receive more information on oral health care.

PMID- 12199892
TI  - Unusual presentation of talon cusp: two case reports.
AB  - Talon cusp is an uncommon odontogenic anomaly comprising of an accessory cusp
      like structure, usually observed on the palatal surfaces of maxillary incisors.
      Two uncommon presentations of talon cusp, occurring on a mandibular incisor and
      on a supernumerary tooth in the maxilla, are reported.

PMID- 12199893
TI  - Multifactorial analysis of the aetiology of craniomandibular dysfunction in
      children.
AB  - OBJECTIVES: It is generally accepted that the aetiology of craniomandibular
      dysfunction (CMD) is multifactorial. Different types of malocclusion, oral
      parafunctions especially bruxism, trauma of the mandible or temporomandibular
      joint (TMJ) and emotional stress are known aetiologic factors. Research has been
      conducted into the relationship between each of these aetiologic factors and the
      signs and symptoms of CMD. However, such an approach does not control for the
      simultaneous effect of other factors responsible for the development of the
      dysfunction. The purpose of this study was to investigate the effect of each
      aetiologic factor on the signs and symptoms of CMD in children, controlling for
      the effect of all other known factors by means of a multifactorial analysis.
      METHODS: A sample of 314 children, aged 6-8 years, was examined clinically for
      signs of CMD and morphologic and functional malocclusion. Symptoms of CMD and
      oral parafunctions were recorded by the same investigator in an interview.
      Emotional stress was measured through urinary catecholamines including
      epinephrine, norepinephrine and dopamine, detected in a 24-h urine sample, using
      high performance liquid chromatography. A questionnaire was distributed to the
      parents to collect information regarding socioeconomic factors and the history of
      dentofacial injuries. A logistic multiple regression was carried out to estimate
      the partial effect of each aetiologic factor. A 95% probability level was used.
      RESULTS: Posterior crossbite with lateral shift significantly affected the
      probability of child developing deviation of the mandible on opening. Similarly,
      posterior crossbite and epinephrine had a significant impact on TMJ tenderness,
      overjet had an effect on clicking, clenching and biting of objects had an effect
      on muscle tenderness, and lip/cheek biting influenced dysfunctional opening. Of
      the symptoms reported, pain on wide opening was affected significantly by
      lip/cheek biting. CONCLUSION: On the basis of these results, it can be suggested
      that parafunctional and some structural and psychological factors may increase
      the probability of the child developing the signs and symptoms of CMD.

PMID- 12199894
TI  - Seminars on controversial issues. A review of the pharmacological approach to the
      management of dental anxiety in children.
AB  - This paper aims to review the existing literature on the pharmacology of a number
      of sedative drugs used in the management of dental anxiety in the conscious child
      patient. Pharmacological agents may be used as a complement to behavioural
      techniques to assist in the management of anxiety in some paediatric dental
      patients. Their use may also be especially indicated in children with
      disabilities. These agents are usually sedative in action and do not, in
      themselves, eliminate anxiety but merely enhance patient acceptance by reducing
      arousal and modifying anticipation of danger. The agents used are varied and
      diverse and include nitrous oxide, benzodiazepines and narcotics. Nitrous oxide
      has proved to be of particular value but carries a degree of risk for the
      operating staff. Amongst the benzodiazepines, Midazolam has been used more
      frequently in recent years. It may be given by a variety of routes, including
      intra-nasally. Dentists who employ sedative agents and techniques should be
      familiar with the pharmacology of the agents selected, be cognisant of the risks
      and benefits of the technique employed and be able to manage any adverse events
      that may arise through their use.

PMID- 12199895
TI  - The use of sedation while treating paediatric dental patients in Israel.

PMID- 12199896
TI  - Pharmacological approach to the management of dental anxiety in children-
      comments from a Scandinavian point of view.

PMID- 12199898
TI  - UK National Clinical Guidelines in Paediatric Dentistry. Managing anxious
      children: the use of conscious sedation in paediatric dentistry.

PMID- 12199900
TI  - Molecular diagnostics in rare syndromes.

PMID- 12199906
TI  - Epstein-Barr virus encoded nuclear protein EBNA-3 binds a novel human uridine
      kinase/uracil phosphoribosyltransferase.
AB  - BACKGROUND: Epstein-Barr virus (EBV) infects resting B-lymphocytes and transforms
      them into immortal proliferating lymphoblastoid cell lines (LCLs) in vitro. The
      transformed immunoblasts may grow up as immunoblastic lymphomas in immuno
      suppressed hosts. RESULTS: In order to identify cellular protein targets that may
      be involved in Epstein-Barr virus mediated B-cell transformation, human LCL cDNA
      library was screened with one of the transformation associated nuclear antigens,
      EBNA-3 (also called EBNA-3A), using the yeast two-hybrid system. A clone encoding
      a fragment of a novel human protein was isolated (clone 538). The interaction was
      confirmed using in vitro binding assays. A full-length cDNA clone (F538) was
      isolated. Sequence alignment with known proteins and 3D structure predictions
      suggest that F538 is a novel human uridine kinase/uracil
      phosphoribosyltransferase. The GFP-F538 fluorescent fusion protein showed a
      preferentially cytoplasmic distribution but translocated to the nucleus upon co
      expression of EBNA-3. A naturally occurring splice variant of F538, that lacks
      the C-terminal uracil phosphoribosyltransferase part but maintain uridine kinase
      domain, did not translocate to the nucleus in the presence of EBNA3. Antibody
      that was raised against the bacterially produced GST-538 protein showed
      cytoplasmic staining in EBV negative Burkitt lymphomas but gave a predominantly
      nuclear staining in EBV positive LCL-s and stable transfected cells expressing
      EBNA-3. CONCLUSION: We suggest that EBNA-3 by direct protein-protein interaction
      induces the nuclear accumulation of a novel enzyme, that is part of the
      ribonucleotide salvage pathway. Increased intranuclear levels of UK/UPRT may
      contribute to the metabolic build-up that is needed for blast transformation and
      rapid proliferation.

PMID- 12199908
TI  - Retrovirus-delivered siRNA.
AB  - BACKGROUND: The ability of transfected synthetic small interfering (si) RNAs to
      suppress the expression of specific transcripts has proved a useful technique to
      probe gene function in mammalian cells. However, high production costs limit this
      technology's utility for many laboratories and experimental situations. Recently,
      several DNA-based plasmid vectors have been developed that direct transcription
      of small hairpin RNAs, which are processed into functional siRNAs by cellular
      enzymes. Although these vectors provide certain advantages over chemically
      synthesized siRNAs, numerous disadvantages remain including merely transient
      siRNA expression and low and variable transfection efficiency. RESULTS: To
      overcome several limitations of plasmid-based siRNA, a retroviral siRNA delivery
      system was developed based on commerically available vectors. As a pilot study, a
      vector was designed to target the human Nuclear Dbf2-Related (NDR) kinase. Cells
      infected with the anti-NDR siRNA virus dramatically downregulate NDR expression,
      whereas control viruses have no effect on total NDR levels. To confirm and extend
      these findings, an additional virus was constructed to target a second gene,
      transcriptional coactivator p75. CONCLUSION: The experiments presented here
      demonstrate that retroviruses are efficient vectors for delivery of siRNA into
      mammalian cells. Retrovirus-delivered siRNA provides significant advancement over
      previously available methods by providing efficient, uniform delivery and
      immediate selection of stable "knock-down" cells. This development should provide
      a method to rapidly assess gene function in established cell lines, primary
      cells, or animals.

PMID- 12199907
TI  - The tripeptide FEG ameliorates systemic inflammatory responses to rat intestinal
      anaphylaxis.
AB  - BACKGROUND: Food allergies are generally associated with gastrointestinal upset,
      but in many patients systemic reactions occur. However, the systemic effects of
      food allergies are poorly understood in experimental animals, which also offer
      the opportunity to explore the actions of anti-allergic drugs. The tripeptide D
      phenylalanine-D-glutamate-Glycine (feG), which potentially alleviates the
      symptoms of systemic anaphylactic reactions, was tested to determine if it also
      reduced systemic inflammatory responses provoked by a gastric allergic reaction.
      RESULTS: Optimal inhibition of intestinal anaphylaxis was obtained when 100
      microg/kg of feG was given 20 min before the rats were challenged with antigen.
      The increase in total circulating neutrophils and accumulation of neutrophils in
      the heart, developing 3 h and 24 h, respectively, after antigen challenge were
      reduced by both feG and dexamethasone. Both anti-inflammatory agents reduced the
      increase in vascular permeability induced by antigen in the intestine and the
      peripheral skin (pinna), albeit with different time courses. Dexamethasone
      prevented increases in vascular permeability when given 12 h before antigen
      challenge, whereas feG was effective when given 20 min before ingestion of
      antigen. The tripeptide prevented the anaphylaxis induced up regulation of
      specific antibody binding of a cell adhesion molecule related to neutrophil
      activation, namely CD49d (alpha4 integrin). CONCLUSIONS: Aside from showing that
      intestinal anaphylaxis produces significant systemic inflammatory responses in
      non-intestinal tissues, our results indicate that the tripeptide feG is a potent
      inhibitor of extra-gastrointestinal allergic reactions preventing both acute (30
      min) and chronic (3 h or greater) inflammatory responses.

PMID- 12199909
TI  - Functional expression of NF1 tumor suppressor protein: association with keratin
      intermediate filaments during the early development of human epidermis.
AB  - BACKGROUND: NF1 refers to type 1 neurofibromatosis syndrome, which has been
      linked with mutations of the large NF1 gene. NF1 tumor suppressor protein,
      neurofibromin, has been shown to regulate ras: the NF1 protein contains a GTPase
      activating protein (GAP) related domain which functions as p21rasGAP. Our studies
      have previously demonstrated that the NF1 protein forms a high affinity
      association with cytokeratin 14 during the formation of desmosomes and
      hemidesmosomes in cultured keratinocytes. METHODS: The expression of NF1 protein
      was studied in developing human epidermis using western transfer analysis,
      indirect immunofluorescence, confocal laser scanning microscopy, immunoelectron
      microscopy, and in situ hybridization. RESULTS: The expression of NF1 protein was
      noted to be highly elevated in the periderm at 8 weeks estimated gestational age
      (EGA) and in the basal cells at 8-14 weeks EGA. During this period, NF1 protein
      was associated with cytokeratin filaments terminating to desmosomes and
      hemidesmosomes. NF1 protein did not display colocalization with alpha-tubulin or
      actin of the cytoskeleton, or with adherens junction proteins. CONCLUSIONS: These
      results depict an early fetal period when the NF1 tumor suppressor is abundantly
      expressed in epidermis and associated with cytokeratin filaments. This period is
      characterized by the initiation of differentiation of the basal cells, maturation
      of the basement membrane zone as well as accentuated formation of selected
      cellular junctions. NF1 tumor suppressor may function in the regulation of
      epidermal histogenesis via controlling the organization of the keratin
      cytoskeleton during the assembly of desmosomes and hemidesmosomes.

PMID- 12199910
TI  - Fast relapse and high drop out rate of 48 weeks daily interferon monotherapy in
      HIV-infected patients with chronic hepatitis C.
AB  - BACKGROUND: The standard of care for HCV Hepatitis is the combination of
      interferon (IFN) plus Ribavirin. In HIV patients the use of this combination
      therapy may induce drug interactions, and reduces the adherence to HAART. The aim
      of this study is to evaluate safety and efficacy of a 48 weeks daily dose IFN
      schedule. METHODS: We evaluated 50 coinfected patients; alpha IFN 2a was
      administered at a dose of 3 MU daily. The baseline values were the following :
      CD4+ 515 cells/mmc (mean); HIV-RNA <50 copies/ml in all patients; HCV-RNA 28, 3 x
      106 copies/ml. RESULTS: At 48 weeks, 10 patients (20%) achieved a biochemical and
      virological response according to an intention to treat analysis.Twenty four
      patients (48%) underwent a drop-out mainly by side effects related to overlapping
      toxicity of interferon and antiretroviral therapy. All the patients, who
      responded to the treatment, showed a fast relapse one month after the end of
      treatment. CONCLUSION: Although our results demonstrated a very poor outcome and
      a bad tolerance to interferon monotherapy, this approach should not be dropped
      out, mainly in patients at high risk for side effects and in those with cirrhosis
      who do not tolerate or are at increased risk for the use of ribavirin.

PMID- 12199912
TI  - Long-term experimental evolution in Escherichia coli. X. Quantifying the
      fundamental and realized niche.
AB  - BACKGROUND: Twelve populations of the bacterium, Escherichia coli, adapted to a
      simple, glucose-limited, laboratory environment over 10,000 generations. As a
      consequence, these populations tended to lose functionality on alternative
      resources. I examined whether these populations in turn became inferior
      competitors in four alternative environments. These experiments are among the
      first to quantify and compare dimensions of the fundamental and realized niches.
      RESULTS: Three clones were isolated from each of the twelve populations after
      10,000 generations of evolution. Direct competition between these clones and the
      ancestor in the selective environment revealed average fitness improvements of
      approximately 50%. When grown in the wells of Biolog plates, however, evolved
      clones grew 25% worse on average than the ancestor on a variety of different
      carbon sources. Next, I competed each evolved population versus the ancestor in
      four foreign environments (10-fold higher and lower glucose concentration, added
      bile salts, and dilute LB media). Surprisingly, nearly all populations were more
      fit than the ancestor in each foreign environment, though the margin of
      improvement was least in the most different environment. Most populations also
      evolved increased sensitivity to novobiocin. CONCLUSIONS: Reduced functionality
      on numerous carbon sources suggested that the fundamental niche of twelve E. coli
      populations had narrowed after adapting to a specific laboratory environment.
      However, in spite of these results, the same populations were competitively
      superior in four novel environments. These findings suggest that adaptation to
      certain dimensions of the environment may compensate for other functional losses
      and apparently enhance the realized niche.

PMID- 12199913
TI  - [Positron emission tomography in respiratory medicine].

PMID- 12199914
TI  - [Increased upper airway resistance syndrome: a specific diagnosis?].

PMID- 12199911
TI  - Telomere formation on macronuclear chromosomes of Oxytricha trifallax and O.
      fallax: alternatively processed regions have multiple telomere addition sites.
AB  - BACKGROUND: Ciliates employ massive chromatid breakage and de novo telomere
      formation during generation of the somatic macronucleus. Positions flanking the
      81-MAC locus are reproducibly cut. But those flanking the Common Region are
      proposed to often escape cutting, generating three nested macronuclear
      chromosomes, two retaining "arms" still appended to the Common Region. Arm-distal
      positions must differ (in cis) from the Common Region flanks. RESULTS: The Common
      Region-flanking positions also differ from the arm-distal positions in that they
      are "multi-TAS" regions: anchored PCR shows heterogeneous patterns of telomere
      addition sites, but arm-distal sites do not. The multi-TAS patterns are
      reproducible, but are sensitive to the sequence of the allele being processed.
      Thus, random degradation following chromatid cutting does not create this
      heterogeneity; these telomere addition sites also must be dictated by cis-acting
      sequences. CONCLUSIONS: Most ciliates show such micro-heterogeneity in the
      precise positions of telomere addition sites. Telomerase is believed to be
      tightly associated with, and act in concert with, the chromatid-cutting nuclease:
      heterogeneity must be the result of intervening erosion activity. Our "weak
      sites" hypothesis explains the correlation between alternative chromatid cutting
      at the Common Region boundaries and their multi-TAS character: when the chromatid
      breakage machine encounters either a weak binding site or a weak cut site at
      these regions, then telomerase dissociates prematurely, leaving the new end
      subject to erosion by an exonuclease, which pauses at cis-acting sequences;
      telomerase eventually heals these resected termini. Finally, we observe TAS
      positioning influenced by trans-allelic interactions, reminiscent of
      transvection.

PMID- 12199916
TI  - [Use and comprehensibility of statistical analysis in Archivos de
      Bronconeumologia (1970-1999)].
AB  - OBJECTIVES: To describe the type of statistical analysis used most often in
      original research articles published in Archivos de Bronconeumologia, and the
      evolution of statistical analysis over time in terms of complexity. To determine
      comprehensibility, taking bivariate analysis as the reference threshold. MATERIAL
      AND METHODS: All articles published in the original research section of Archivos
      de Bronconeumologia from 1970 through 1999 were reviewed manually. For each
      article we recorded the category or categories of statistical analysis and its
      comprehensibility (with a reference threshold set at category 7). We studied the
      following factors: year of publication, type of analysis, comprehensibility,
      maximum category achieved, subject area and number of authors. RESULTS: Eight
      hundred sixty original articles, with a mean 5 2 authors per article were
      examined. The maximum category reached was a mean 4.15 4.61. The three types of
      analysis used most often in all articles were category 1 (descriptive only) at
      49.4%, category 2 (t and z tests) at 26.4% and category 3 (bivariate tables) at
      19.1%. Among the more complex analytical categories, the most often used were
      analysis of variance (category 8) at 9%, survival analysis (category 16) at 6.2%,
      and non-parametric correlations at 3.4%. Comparing results by decade, the
      proportion of articles with only descriptive analysis fell from 74% in the
      seventies to 63.9% in the eighties and to 36.1% in the nineties (90s vs. 80s, p <
      0.05; 90s vs. 70s, p < 0.05; 80s vs. 70s, p < 0.05). The use of statistics from
      categories 3 and 6 increased (p < 0.05), and the use of the more complex
      categories 8, 10, 11 and 16 increased (p < 0.05). Comprehensibility decreased
      significantly to 68.1% in the 90s in relation to increased complexity of
      analysis. CONCLUSIONS: The complexity of statistical analysis in articles
      published in Archivos de Bronconeumologia increased over time, while
      comprehensibility decreased.

PMID- 12199915
TI  - [Smoking cessation and bupropion: anxiety and depression as predictors of
      therapeutic efficacy].
AB  - Smoking and depression are related. Bupropion, the first non-nicotinic drug that
      is an effective treatment in smoking cessation, is a tricyclic antidepressant
      that inhibits neuronal uptake of serotonin, dopamine and norepinephrine in the
      thalamic nuclei. OBJECTIVE: To assess if certain personality factors (anxiety or
      depression) might predict the efficacy of bupropion for smoking cessation.
      METHOD: The study was carried out in two smoking cessation clinics in Madrid and
      Barcelona. Fifty patients (21 men) declaring the desire to quit smoking were
      enrolled. Their mean age was 43.6 years (SD 8.75). The patients were treated with
      300 mg of bupropion per day for one month and expired CO was monitored for 6
      months. Personality factors were assessed on a hospital anxiety and depression
      scale (HADS). We evaluated whether there was a significant difference in HADS
      scores for patients who were still not smoking after 6 months and those who had
      not managed to quit. RESULTS: The 50 patients were smokers of a mean 39 packs per
      year (SD 17.82) and had mean scores of 7.4 (SD 4.15) for anxiety and 5.8 (SD
      3.93) for depression. Four patients (8%) were unable to complete the study. After
      one month, 28% of the patients smoked, after 3 months 56% smoked and after 6
      months 58% still smoked. The patients who smoked during the first month had
      higher depression scores than did the non-smokers (p = 0.03). After 3 and 6
      months the patients who had managed to continue not smoking were those who had
      higher anxiety scores than did those who still smoked (p = 0.0052 at 3 months and
      p = 0.017 at 6 months). CONCLUSION: Patients who responded better to treatment
      with bupropion after 6 months of follow-up were those with higher anxiety scores
      on the HADS. Depression levels influenced outcome only during the first month.

PMID- 12199917
TI  - [Hormone expression and opioid receptors in fetal and adult lung].
AB  - OBJECTIVES: To describe the cellular distribution and level of expression of
      certain hormones and opioid receptors during fetal development and in the lung of
      the healthy adult. METHOD: We sampled lung tissue from fetuses at three stages of
      development (pseudoglandular, canalicular and saccular) (3 samples per stage),
      from newborn infants (3), from 10-month-old infants (2) and from adults (3) who
      had died without lung disease. After specific immunohistochemical staining for
      hormones (calcitonin, parathormone, serotonin and adrenocorticotropic hormone -
      ACTH) and opioid receptors, we assessed the percentage of positive cells for each
      cell type in each sample. RESULTS: Serotonin is the first to appear
      (pseudoglandular stage in isolated neuroendocrine cells) and it disappears later.
      Calcitonin appears in the canalicular stage in neuroendocrine and lung cells.
      Expression is at its peak at birth and is less in the adult lung. We found no
      ACTH or parathormone production. Opioid receptors appear in the canalicular stage
      and peak at birth. In adult lung, bronchiolar muscle and mesothelial cells, only
      delta-type opioid receptors are present. CONCLUSIONS: Pulmonary hormone secretion
      is significant during fetal development and peaks at birth. Calcitonin is the
      main hormone produced in the fetal lung. Opioid receptors are present during
      fetal development in various types of cells and peak at birth. An understanding
      of the expression of active substances could have therapeutic relevance in
      certain conditions, such as bronchial asthma or respiratory distress syndrome in
      the child.

PMID- 12199918
TI  - [Role of flexible bronchoscopy in the re-expansion of persistent atelectasis in
      children].
AB  - OBJECTIVE: To evaluate the efficacy of flexible bronchoscopy plus bronchoalveolar
      lavage for the reexpansion of persistent atelectasis (course longer than 3 weeks)
      in children. PATIENTS AND METHODS: Retrospective review of the records of 83
      children who underwent flexible fiberoptic bronchoscopy plus bronchoalveolar
      lavage for persistent atelectasis. Three categories of evolution were established
      for radiologic assessment: a) full re-expansion (full improvement over the
      initial image); b) partial re-expansion (decreased atelectasis of between 50% and
      100%); and c) no change (if the decrease was less than 50% of the initial image).
      RESULTS: Endoscopy revealed mucus plugs in 54 patients (65%); bronchial
      malformations in 16 (19%); bronchial stenosis in 5 (6%); normal airways in 5 (6%)
      and other findings in 3 (4%). Radiologic changes after bronchoscopy showed full
      expansion for 34 patients (41%), partial re-expansion for 28 (34%) and no changes
      for 21 (25%). CONCLUSION: Flexible bronchoscopy plus bronchoalveolar lavage for
      the re-expansion of persistent atelectasis is useful in a high percentage of
      children.

PMID- 12199919
TI  - [Non-invasive ventilation in patients with severe hypercapnic encephalopathy in a
      conventional hospital ward].
AB  - OBJECTIVE: To report our experience with non-invasive ventilation (NIV) at two
      levels of pressure (Bi-PAP) on a general respiratory medicine ward with patients
      in hypercapnic impaired consciousness and/or coma who had not previously been in
      an intensive care unit (ICU). METHODS: This was a prospective study of 13
      patients, mean age 81 years (65-96), treated with NIV through a face mask. Ten
      had chronic obstructive pulmonary disease, with a mean FEV1 in stable condition
      of 35.2 14.6%. Glasgow scores upon admission were >/= 7. Arterial gases were
      monitored until suspension of NIV. RESULTS: After NIV for a mean 19 5 h/day in
      the first 48 hours and later of 6 1 h/day until a total of 74 9 h, 9 patients
      (69%) survived. The mean initial pH for these patients was 7.17 0.028 and the
      mean initial pCO2 was 101 9 mm Hg. In 7 cases (78%), coma was reversed in the
      first 48 h and a significant improvement in pH was observed in the 12-24 h
      analysis. Mean pH upon discharge was 7.44 0.013 and mean pCO2 was 54 2.8 mmHg.
      Four patients died, even though their initial or subsequent arterial gases at 12
      24 h were not significantly different from those of the survivors. CONCLUSION:
      NIV on a general respiratory medicine ward can offer an alternative to oro
      tracheal intubation for patients with hypercapnic impaired consciousness and/or
      coma who do not meet the criteria for admission to the ICU.

PMID- 12199920
TI  - [Multiresistant pathogens in cystic fibrosis].

PMID- 12199921
TI  - [New therapeutic targets and strategies in lung cancer].

PMID- 12199922
TI  - [Minimally invasive video thoracoscopic correction of pectus excavatum].
AB  - Pectus excavatum, the most common congenital deformity of the chest wall, has
      esthetic, psychological and social repercussions as well as a slight impact on
      pulmonary function. Treatment is surgical and is carried out for esthetic
      purposes in most cases. The most commonly applied surgical technique is based on
      the one originally described by Ravitch: sub-perichondrial, bilateral
      chondrectomy and sternal osteotomy. In 1997, however. Nuss described a minimally
      invasive approach to correction by means of a support bar. Our objective was to
      perform minimally invasive correction of pectus excavatum using a substernal
      extrapleural approach guided by video-assisted thoracoscopy. We treated three
      patients over 15 years of age without surgical complications. In all three cases,
      the minimally invasive technique corrected the pectus excavatum with excellent
      esthetic results. Both the path of insertion and duration were shorter with the
      described approach than with traditional surgery. Video images facilitated
      extrapleural insertion of the bar and minimized complications.

PMID- 12199924
TI  - [Dendriform pulmonary ossification associated with idiopathic pulmonary
      fibrosis].
AB  - Diffuse pulmonary ossification, a rare condition characterized by metaplastic
      ossification of the lung, is usually associated with diseases causing diffuse
      pulmonary lesions. Two types dendriform and nodular have been identified. In
      dendriform ossification, the less common type, osseous ramifications occur along
      the distal airways, with occasional islets of bone marrow. We report a case of
      diffuse dendriform pulmonary ossification associated with idiopathic pulmonary
      fibrosis. The diagnosis was based on histological examination, which demonstrated
      multiple nodules and ramified osseous spicules around the lung, mainly at the
      lower lobes, where the fibrotic lesions were also most evident.

PMID- 12199923
TI  - [Simultaneaous bilateral pulmonary metastasectomy of carcinoma of the sweat
      glands].
AB  - A 51-year-old woman with carcinoma of the right axillary sweat glands was treated
      by radical surgery and radiotherapy. Six years later she developed multiple
      bilateral lung metastases. Nine nodes were resected from both lungs using a
      clamshell approach (bilateral transsternal, anterolateral thoracotomy). After
      surgery, the patient received 6 cycles of adjuvant chemotherapy with cisplatin
      and 5-fluoruracil. Three years after treatment, no intrathoracic recurrences had
      occurred and the patient was asymptomatic, with good quality of life.

PMID- 12199925
TI  - [Giant chondrosarcoma of the chest wall].

PMID- 12199926
TI  - [Mycobacterium xenopi: a rare mycobacterium?].

PMID- 12199927
TI  - [Inhalation therapy without instruction: failure foreseen].

PMID- 12199928
TI  - [Multicenter prospective study of respiratory patient education and instruction
      in the use of inhalers (EDEN study)].
AB  - OBJECTIVES: To evaluate patients' knowledge of the inhalers they use and to
      assess the effect of knowledge acquired in an instruction session on correct
      technique. MATERIAL AND METHODS: Multicentric, prospective, descriptive study
      before and after one instruction session dealing with the technique to apply in
      using an inhaler: a pressurized canister, an inhalation chamber Autohaler, or one
      of two dry powder inhalers (the Turbuhaler or the Accuhaler). We studied 349
      patients who used their inhalers regularly to treat their respiratory diseases.
      After assessing their theoretical knowledge of the airways (common), of the
      particular device they used, and their inhalation technique, we gave instruction
      in correct technique. Both types of knowledge were then evaluated 2 and 8 months
      after instruction. RESULTS: Before instruction, common theoretical knowledge was
      3.2 (1) on a 6-point scale and knowledge of the device used was 2.7(1) on a 4
      point scale. Technique was assessed as 77 (21) on a 100-point scale. After
      instruction both theoretical knowledge and technique improved significantly.
      Common knowledge after instruction was assessed as 5.1 (1) at 2 months and 5.2
      (1) at 8 months; knowledge of the inhaler was 3.5 (0.6) and 3.6 (0.7),
      respectively. Technique was assessed at 95 (11) and 96 (11) at 2 and 8 months,
      respectively. CONCLUSIONS: The EDEN study demonstrates that knowledge of inhalers
      in a large sample of the population of respiratory disease patients in Spain,
      although acceptable, can be improved by an appropriate instruction program. After
      a standardized instruction program, correct use of all the inhalers studied was
      achieved. We believe that we thereby contribute to improving symptoms and quality
      of life of respiratory disease patients.

PMID- 12199929
TI  - [Usefulness of teaching how to manage the pressurized canister and the Turbuhaler
      system in hospitalized patients].
AB  - OBJECTIVE: [corrected] To assess knowledge of how to use a pressurized canister
      (PC) or Turbuhaler (TB) systems and to evaluate the usefulness of giving
      technical instruction to hospitalized patients, analyzing chronic obstructive
      pulmonary disease (COPD) patients according to degree of obstruction. METHOD: We
      evaluated the use of the PC by 107 consecutive patients and the TB by 79 patients
      upon their admission to the respiratory medicine ward, with reference to the
      guidelines of the Spanish Society of Respiratory Medicine and Thoracic Surgery.
      We then evaluated the usefulness of instruction PC or TB technique. We recorded
      age, sex, underlying respiratory disease, the patient's opinion and time in years
      the patient had been using the inhaler, FEV1, and technique upon admission and
      after instruction during the hospital stay. RESULTS: Only 19% of the patients
      used the PC and 32% of the TB patients used their inhaler correctly at first.
      After instruction, the rates of correct use improved to 42% and 70% for the PC
      and TB, respectively, over the course of an approximately 4-day hospital stay.
      Among the PC users, 77% believed they were performing the maneuver correctly. All
      steps for both inhalers improved, as the number of errors decreased, particularly
      errors considered most relevant (coordination of the trigger and inspiration from
      the PC or full expiration and breath holding with both systems). The number of
      correct techniques at the end of the study was similar for all levels of COPD
      obstruction, and particularly for those using the TB. CONCLUSIONS: Most patients
      admitted to our ward were unable to use either inhaler correctly, with incorrect
      use of the PC being particularly evident. It is possible to improve performance,
      however, if we take care to teach patients in short instruction sessions. This is
      true for all COPD patients, regardless of level of obstruction. Our results
      demonstrate that a program of instruction during a patient's hospital stay is
      both feasible and important.

PMID- 12199930
TI  - [Interleukin 10 and tumor necrosis factor alpha gene expression in respiratory
      and peripheral muscles. Relation to sarcolemmal damage].
AB  - BACKGROUND: Tumor necrosis factor alpha (TNF-alpha) has been implicated in loss
      of muscle mass in chronic obstructive pulmonary disease and other consumptive
      processes. TNF-alpha production would be related to inflammation arising from
      pulmonary disease itself or, alternatively, from smoking, and would be carried to
      the muscle through the blood stream. However, it has also been suggested that TNF
      alpha may be expressed directly in muscle tissue. Regardless the site of
      production of TNF-alpha, its relation to subsequent muscle damage is unclear.
      OBJECTIVE: We studied the expression of TNF-alpha and an interleukin inhibitor of
      its production (IL-10) in the main respiratory muscles and a peripheral muscle in
      the dog. METHOD: Nine young, male Beagle dogs were included. From all animals we
      obtained a biopsy of the diaphragm (Dph) and external intercostal (ExtI) muscles
      and a leg muscle (internal vastus of the quadriceps, IntV). TNF-alpha and IL-10
      gene expressions were measured through the analysis of messenger RNA levels,
      using reverse transcription and polymerase chain reaction. We also assessed
      sarcolemmal damage using intracellular fibronectin detection
      (immunohistochemistry). RESULTS: The expression of both cytokines showed wide
      interindividual variability. On the one hand, TNF-alpha (was very low in Dph and
      ExtI (0.02 0.03 and 0.05 0.06 a.u., respectively), but relatively high in the
      IntV (0.14 0.08 a.u.). IL-10 expression, on the other hand was low in the Dph
      (0.06 0.05 a.u.) and slightly higher in the ExtI (2.7 1.9 a.u., p < 0.01) and
      IntV (1.6 1.7 a.u.). Sarcolemmal damage was minimal in all three muscles and was
      related to TNF-alpha expression in the peripheral muscle (r = 0.682, p < 0.05).
      CONCLUSIONS: 1) TNF-alpha and IL-10 appear to be constitutively expressed within
      the skeletal muscle in dogs. 2) Basal TNF-alpha expression is lower in
      respiratory muscles than in peripheral muscles. 3) The expression in the latter
      is related to membrane damage.

PMID- 12199932
TI  - [Controversies in the use of beta-agonists in the treatment of acute asthma].

PMID- 12199931
TI  - [Prevalence of anti-smoking counseling in a primary care clinic: comparison of
      patient charts with patient reports].
AB  - OBJECTIVE: To estimate the prevalence of anti-tobacco counseling of smokers.
      DESIGN: Cross-sectional, descriptive study. SETTING: Primary care center.
      SUBJECTS: Random sample of 1,228 patients over 14 years of age who visited a
      doctor or nurse over the year prior to the study. MEASURES: 1) Telephone
      interview: age, sex, medical history, education, smoking status, number of
      cigarettes daily, frequency of visits to the doctor, receipt of anti-smoking
      advice, reason for seeking medical care, the type of professional who saw the
      patient and the patient's attitude toward the advice. 2) Patient chart: record of
      advice given. RESULTS: Five hundred sixty-three questionnaires were valid.
      Smokers made up 37% (95% CI 33%-41%) of the population, with a mean age of 33.37
      (18.14 years; 39.1% of men and 36.1% of the women smoked. The prevalence of anti
      smoking counseling according to the patient was 62.3% (95% CI: 56-69%). There was
      little agreement between counseling as reported by the patients and as recorded
      in the patient's chart (kappa index 0.149, p = 0.01). The mean age of patients
      advised to quit (34.8 + 10.89 years) was higher than that of those who did not
      receive advice to quit. Seventy percent of patients who came to the clinic more
      than 3 times per year reported having been advised to quit, whereas 50% of those
      who came fewer than 3 times per year were so advised. Among patients who were
      advised to quit, 78.3% said the advice came when they had come to the clinic
      about matters related to smoking. According to patients, advice was usually given
      by a doctor (76.7%). After being advised to quit, 32.55% of the smokers did so,
      6.2% of them for longer than 6 months. CONCLUSIONS: The percentage of smokers at
      our clinic is similar to that in the general population. The prevalence of anti
      smoking counseling reported by the user is greater than that reported in other
      studies, but can clearly be improved. Anti-smoking advice is underreported in our
      patient charts in comparison with patient reports. The patients who receive
      advice most often are those who come to the clinic frequently and those who come
      for smoking-related problems. Physicians are the professionals who most often
      advise patients on smoking.

PMID- 12199933
TI  - [The divine cork oak].

PMID- 12199934
TI  - [Pneumologists: Where are we going and where have we come from?].

PMID- 12199935
TI  - [Superior vena cava syndrome secondary to intracavitary implantation of a
      pacemaker].
AB  - The appearance of superior vena cava syndrome secondary to benign disease is
      rare, and it is extremely rare for this condition to develop as a result of the
      presence of intraluminal catheters. We report two cases of superior vena cava
      syndrome secondary to implantation of intracavitary pacemakers. We discuss
      different types of treatment.

PMID- 12199936
TI  - [Spontaneous, massive primary pneumothorax in both lungs].
AB  - Primary spontaneous pneumothorax in both lungs simultaneously is rare. We report
      the case of a 22-year-old man with no relevant medical history who came to the
      emergency room in critical condition after suffering simultaneous massive
      pneumothorax in both lungs. After a pleural drain was inserted in each
      hemithorax, elective surgery was prescribed because of the bilaterality and
      severity of the pneumothorax. Sequential video thoracoscopic surgery was
      performed in a single session, during which small blebs were identified at both
      lung vertices. The blebs were resected and pleural abrasion performed.
      Postoperative recovery was unremarkable. The patient was discharged four days
      after surgery. Five years later, the patient was asymptomatic, having experienced
      no recurrences.

PMID- 12199937
TI  - [Pleural empyema due to Salmonella enteritidis].

PMID- 12199938
TI  - [Iatrogenic pneumothorax caused by migration of a Kirschner needle].

PMID- 12199939
TI  - ['Narcolepsy, sleep apnea or inadequate diagnostic technology?].

PMID- 12199940
TI  - [Asthma and respiratory syncytial virus. Myth or reality?].

PMID- 12199941
TI  - [Prevention of cytomegalovirus in preterm neonates].

PMID- 12199942
TI  - [Prevalence of iron deficiency in healthy 12-month-old infants].
AB  - BACKGROUND: Iron deficiency is the most prevalent nutritional deficiency among
      infants in industrialized countries. There is ample documentation of both short-
      and long-term adverse effects of iron deficiency. OBJECTIVE: To study the
      prevalence of iron deficiency in 12-month-old infants and to investigate the
      influence of several factors (dietary, growth, etc.) on iron status. MATERIAL AND
      METHODS: A random sample of 94 healthy infants from a basic health district was
      studied. Maternal and perinatal variables, dietary intake and anthropometry were
      assessed at regular intervals from birth to the age of 12 months. Hemoglobin,
      mean corpuscular volume, transferrin saturation and serum ferritin were also
      evaluated. RESULTS: The prevalence of iron deficiency was 9.6 % and that of iron
      deficiency anemia was 4.3 %. Of the nine infants with iron deficiency, four had
      been breast-fed for more than 6 months with late introduction of complementary
      foods and another had not been fed an iron-fortified formula while the 85
      children without iron deficiency had received an appropriate diet (p < 0.05).
      Weight increase in the first year of life was significantly and positively
      correlated with hemoglobin and serum ferritin. CONCLUSIONS: Iron deficiency is
      relatively common in 12-month-old-infants but is limited to groups with
      inadequate feeding practices. Iron deficiency screening should be performed only
      in children with risk factors and/or inadequate diets.

PMID- 12199943
TI  - [Influence of gypsy ethnicity on hospital admission and diagnostic group among
      infants].
AB  - BACKGROUND: Some ethnic groups are thought to have greater resistance to disease.
      However, scientific studies of this phenomenon are lacking in our environment.
      OBJECTIVE: To study hospitalization rates and type of disease among infants
      according to ethnic group. MATERIAL AND METHODS: In 2000, 496 infants aged
      between 1 and 24 months were admitted to our hospital. Using ethnic group as a
      variable, 403 infants (81.25 %) were classified as non-gypsy and 93 (18.75 %) as
      gypsy. Demographic data were used to compare the variables of ethnicity and the
      main diagnostic group. Descriptive statistical analysis of the variables was
      performed. Differences were considered significant when p < 0.05. RESULTS: The
      gypsy group represented 6.51 % of the infant population but accounted for 18.75 %
      of infant admissions (p < 0.05). The gypsy group accounted for 54.83 % of
      readmissions compared with 20.80 % in the non-gypsy group (p < 0.001).
      Respiratory disease was more prevalent in the gypsy group (35.48 %) than in the
      non-gypsy group (22.58 %) (p < 0.05). However, digestive problems were more
      frequent in the non-gypsy group (34.73 %) than in the gypsy group (19.35 %) (p <
      0.05). No statistically significant differences were found in other diagnostic
      groups. CONCLUSION: The differences observed between demographic distribution and
      admission rate contradict the belief that members of the gypsy ethnic group show
      greater disease resistance. The differences in admission rate and diagnostic
      group may be due to socioeconomic, hygienic, health and educational differences
      between both groups. Differences in the prevalence of respiratory disease were
      probably due to overcrowding. Gypsy lifestyle in our population does not confer
      greater disease resistance.

PMID- 12199944
TI  - [Hospitalization rates in infants aged less than 1 year in Madrid and their
      relationship with socioeconomic indicators and infant mortality].
AB  - BACKGROUND: Hospital utilization represents a significant part of all the health
      services offered to the population. Previous studies have demonstrated
      considerable variability in hospital utilization among the pediatric population.
      OBJECTIVE: To describe hospitalization rates in infants aged less than 1 year in
      the municipal districts of the city of Madrid and to analyze their association
      with socioeconomic indicators and infant mortality. METHODS: Ecological study
      with the health district of the city of Madrid as the unit of analysis. The
      following variables were included: overall hospital discharge rates, ambulatory
      care sensitive condition (ACSC) discharge rates and infant mortality rates, as
      well as the percentages of university graduates, without primary education,
      unemployed, without telephone and without tap water. Correlation and multiple
      regression analysis were performed. RESULTS: The mean overall and ACSC discharge
      rates were 280.10 94.09 and 52.65 29.29. Their coefficient of variation was 32.47
      and 55.63. Discharge rates showed significant correlation with the percentage of
      unemployed (0.71), university graduates (-0.66) and those without primary
      education (0.88). ACSC rates were correlated with the percentage of unemployed
      (0.51) and of university graduates (-0.48). The variables included in the
      multiple lineal regression models were the percentage without primary education
      for discharge rates (R2 0.78; p < 0.0000) and the percentage of unemployed for
      ACSC rates (R2 0.26; p < 0.032). CONCLUSIONS: Overall and ACSC discharge rates in
      infants showed significant variation across the health district of the city of
      Madrid. These rates were significantly associated with socioeconomic indicators,
      but not with infant mortality.

PMID- 12199945
TI  - [Rickets in Asian immigrants].
AB  - Although rickets is considered to have practically disappeared in developed
      countries, there is increasing evidence of widespread vitamin D deficiency among
      immigrants. Many studies report rickets and osteomalacia in Asian infants,
      adolescents and pregnant women moving to developed countries with a cooler
      climate. The etiopathogenesis of this disorder of calcium and D vitamin
      metabolism depend mainly on environmental and sociocultural factors, associated
      with low exposure to sunlight and low calcium intake, among other dietary
      factors. Given the recent increase in the number of immigrants to Spain, the
      prevention and treatment of this disease in Asian children and adolescents should
      be reviewed.

PMID- 12199946
TI  - [Domestic humidifiers. What do we know about them?].
AB  - Popular opinion assumes that environmental humidity relieves the clinical
      symptoms of respiratory tract diseases. Various types of home humidifiers are
      available on the market. Parents buy them in the belief that they will improve
      their children's well-being but are usually unaware of whether these devices
      provide a real benefit. Pediatricians should bear the main responsibility in the
      task of informing and guiding families in the use of home humidifiers but general
      lack of knowledge on the subject and the scarcity of published data make this
      task difficult. The aim of this review is to increase general knowledge of home
      humidifiers. We describe what they are, their main types, their basic
      functioning, advantages and disadvantages and the importance of suitable
      maintenance. We define what environmental humidity means, how it can change
      according to temperature and how it can influence human health. Finally, we
      suggest that optimal relative humidity is approximately 40-60 % and that it
      should be measured before using a home humidifier.

PMID- 12199947
TI  - [High-frequency oscillatory ventilation in neonates].
AB  - High-frequency oscillatory ventilation (HFOV) may be considered as an alternative
      in the management of severe neonatal respiratory failure requiring mechanical
      ventilation. In patients with diffuse pulmonary disease, HFOV can applied as a
      rescue therapy with a high lung volume strategy to obtain adequate alveolar
      recruitment. We review the mechanisms of gas exchange, as well as the
      indications, monitoring and special features of the use HVOF in the neonatal
      period.

PMID- 12199948
TI  - [Perinatal cytomegalovirus infection in preterm infants].
AB  - OBJECTIVE: To study the incidence of perinatal cytomegalovirus infection in
      neonates admitted to our hospital in the last three years, as well as the mode of
      transmission, serologic and microbiologic data, and the clinical outcome of these
      infants. METHODS: We performed a retrospective study by reviewing the medical
      records of neonates with a diagnosis of cytomegalovirus infection. RESULTS:
      Twenty-four neonates received this diagnosis. Of these, 21 (85 %) were premature
      infants with a birthweight of less than 1500 gr, representing 6 % of all neonates
      with this birthweight hospitalized during the study period. The percentage of
      transfusion and breastfeeding was high (87 % and 91 %, respectively) and
      consequently the route of transmission could not be identified. Nine neonates (34
      %) presented associated hepatic dysfunction and three (12 %) developed severe
      disease requiring antiviral treatment. CONCLUSIONS: Perinatal cytomegalovirus
      infection is frequent in preterm infants and may be serious. It is important to
      detect cytomegalovirus infections and to develop preventive methods.

PMID- 12199949
TI  - [Deletion 11q23 --> qter (Jacobsen Syndrome) associated with duodenal atresia and
      annular pancreas].
AB  - Jacobsen syndrome is a rare chromosomal disorder due to terminal 11q deletion.
      Prominent features are growth and psychomotor retardation, trigonocephaly and a
      characteristic facial dysmorphism, but many different abnormalities have been
      reported. We present the case of a preterm male. Prenatal ultrasonography was
      suspicious for duodenal atresia. At birth, the boy presented the craniofacial
      features typical of Jacobsen syndrome, together with diffusely spread petechiae
      and talipes equinovarus. Hemogram revealed pancytopenia. Ultrasound examination
      showed left renal agenesis and confirmed the duodenal atresia. Cerebral computed
      tomography scan, electroencephalogram and cardiac studies showed no
      abnormalities. Annular pancreas was found during surgery to correct the duodenal
      atresia. The karyotype was 46,XY,del(11)(q23.2 --> qter), which confirmed
      Jacobsen syndrome.A wide spectrum of clinical features is described in Jacobsen
      syndrome, with phenotype-karyotype correlation. This is the first report of
      duodenal atresia and annular pancreas.

PMID- 12199950
TI  - [Practical guides to nutrition (VII). Functional bowel disorders (equivalent to
      irritable bowel syndrome)].

PMID- 12199951
TI  - [Rickets in Asian immigrants during puberty].
AB  - Rickets usually occurs in the first two years of life and in puberty since
      metabolic demand is increased due to rapid growth in these two critical periods
      of life, when peak bone mass is achieved. Rickets remains one of the most
      prevalent pediatric diseases in developing countries. Although it is considered
      to have disappeared in developed countries, there is increasing evidence of
      widespread vitamin D deficiency among immigrants. There are many reports on
      rickets and osteomalacia in Asian infants, adolescents and pregnant women moving
      from India, Pakistan and Bangladesh to developed countries with a cooler climate.
      We describe three teenagers of Pakistani origin. Clinical presentation included
      limb pains, muscular weakness, knock-knees and seizures. In all three patients,
      biochemical findings included hypocalcemia, raised serum parathormone and
      alkaline phosphatase, and reduced 25-hydroxy vitamin D concentrations. After
      vitamin D treatment and dietary counseling, biochemical findings returned to
      normal and their symptoms improved. Given the recent increase in the number of
      immigrants to Spain, this forgotten disease will probably reappear.

PMID- 12199952
TI  - [Autoimmune hemolytic anemia secondary to cytomegalovirus infection].

PMID- 12199953
TI  - [Polyarthritis and Mediterranean spotted fever].

PMID- 12199954
TI  - [High incidence of untreated decayed permanent teeth among teenagers at social
      risk].

PMID- 12199956
TI  - [Meconium perotonitis with spontaneous resolution].

PMID- 12199955
TI  - [The importance of placental examination. Apropos of a case of neonatal
      meningitis].

PMID- 12199957
TI  - [Infected abdominal cystic lymphangioma: an infrequent cause of acute abdomen].

PMID- 12199958
TI  - [Sinus histiocytosis with massive lymphadenopathy (SHML) with extranodal
      manifestations in an 8-year-old boy].

PMID- 12199959
TI  - [Treatment of pain in a case of osteogenesis imperfecta type III].

PMID- 12199960
TI  - [Erythematoviolaceous nodules and pneumonia].

PMID- 12199961
TI  - [Non-painful arm swelling].

PMID- 12199963
TI  - Allergy: prevention and its problems. The fourth prevention.

PMID- 12199964
TI  - The effect of dithiothreitol on VLA-4 detection in peripheral blood and induced
      sputum cells.
AB  - BACKGROUND: Induced sputum has been shown to be a reliable technique for
      investigating airway inflammation non-invasively. Flow cytometry could provide
      useful information in this area. However, the viscosity of the sample entails the
      use of a mucolytic agent. Dithiothreitol (DDT) is the most frequently used agent
      although it could affect detection of different inflammatory markers. METHODS: To
      measure the effect of DDT on the detection of certain adhesion molecules in
      eosinophils and lymphocytes, sputum was induced from seven non-smoking asthmatic
      and non-asthmatic subjects treated with 0.1 M DDT. The samples were analyzed by
      flow cytometry. Whole blood samples from the same subjects were also processed
      with DTT and analyzed by flow cytometry. RESULTS: Very late activated antigen-4
      (VLA-4) levels on eosinophils in intracellular and surface staining were much
      lower than expected. VLA-4 on lymphocytes was also altered but less so than on
      eosinophils. VLA-4 levels were also decreased on blood cells after DTT treatment.
      No abnormalities were found in the detection of CD29 on eosinophils and the beta7
      chain in lymphocytes. CONCLUSIONS: Flow cytometry could be used as a
      complementary method to induced sputum in the investigation of airway
      inflammation. However, DTT could interfere with the detection of some
      inflammatory markers, as is the case with VLA-4.

PMID- 12199965
TI  - CD34+ cells in peripheral blood of healthy human beings and allergic subjects:
      clue to acute and minimal persistent inflammation.
AB  - BACKGROUND: There is compelling evidence that hemopoietic precursor cells (HPC)
      play a crucial role in establishing cellular inflammation in allergic diseases.
      Increased levels of circulating CD34+ HPC committed to the myeloid lineage have
      been extensively reported in allergic rhinitis, asthma and eczema, whereas CD34+
      cells have been identified within the cellular infiltrates of tissues, at
      peripheral sites of inflammation. METHOD: We conducted a pilot study to evaluate
      CD34+ traffic in the peripheral blood of 22 consecutive patients (13 men and nine
      women; mean age 28.9 years), independently of treatment. The patients presented
      rhinitis, asthma, eczema, urticaria and adverse food reactions of suspected
      allergic origin. Allergic reactions were extrinsic in 18 patients and intrinsic
      in four. In 12 patients who underwent sublingual specific immunotherapy, CD34+
      cells were quantified at enrollment (T0), one year later (T1) and two years later
      (T2). The severity of symptoms was graded on a five-point scale (0 = absence of
      symptoms and 4 = severe symptoms). Twenty healthy human subjects (10 men and 10
      women; mean age 24.5 years) were evaluated as controls. To obtain information
      about the total amount of circulating HPC, independently of the lineage
      commitment (Lin+/-) and the degree of differentiation (CD34bright/dim), we used a
      modification of the Milan protocol of peripheral blood CD34+ cell estimation. The
      cells were analyzed using a BD FACScan or FACSCalibur and the results were
      expressed as the percentage of positive cells. RESULTS: CD34+ cell traffic in the
      control group was very low since all values were < 0.10 (median value: 0.03 %).
      Values in the patient group were increased in both extrinsic and intrinsic forms
      with a median value of 0.25 % (interquartile range: 0.13- 0.33 %). The
      relationship between CD34+ traffic and the severity score was highly significant
      (Spearman's rho = 0.954; test of Ho: CD34; independent score: Pr > t = 0.000).
      CONCLUSIONS: The data reported herein suggest that the method employed is
      effective in assessing acute allergic inflammation, as well as minimal persistent
      inflammation underlying an asymptomatic clinical condition. Evaluation of
      CD34bright/dim peripheral traffic, if confirmed by the outcomes of a multicenter
      study currently being planned together with traditional study of circulating IgE,
      could be a reliable non-invasive laboratory tool for monitoring allergic
      inflammation.

PMID- 12199966
TI  - Is Lolium pollen from an urban environment more allergenic than rural pollen?
AB  - BACKGROUND: Allergy to grass pollen is a highly prevalent allergic disease. Hay
      fever is more predominant in urban than in rural areas, despite the increasingly
      smaller areas of surrounding grassland. The effect of vehicle exhaust pollutants,
      mainly diesel particles, and other industrial sources of atmospheric pollution
      leading to plant damage has been implicated in this phenomenon. OBJECTIVE: This
      study compared the in vivo and in vitro allergenicity of pooled samples of Lolium
      perenne grass pollen harvested from 10 different urban areas with that of samples
      of the same pollen from 10 neighboring rural areas. METHODS: Lolium perenne
      pollen from different parts of a city and from a nearby rural area was harvested
      in 1999 and 2000 during the peak pollination period. Protein composition was
      compared by SDS-PAGE and in vivo and in vitro IgE-binding capacity was compared
      by skin-prick tests, RAST-inhibition and measurement of the major allergen, Lol p
      5. RESULTS: In the two years under study, urban samples contained approximately
      twice the protein content of the rural samples. Biological activity and Lol p 5
      content was higher in urban pollen than in rural pollen and showed differences in
      the two years under study. CONCLUSIONS: The protein content and allergenicity of
      Lolium perenne pollen was higher in urban areas than in rural areas. These
      differences might explain why allergy to grass pollen is more prevalent in urban
      areas. This finding should be taken into account in diagnosis, preventive
      measures and specific immunotherapy.

PMID- 12199967
TI  - Asthma attack severity and urinary concentration of eosinophil X protein in
      children.
AB  - OBJECTIVE: Determination of the urinary concentration of eosinophil protein X (U
      EPX) may objectively predict the severity and activity of asthma in children.
      METHODS: Concentrations of U-EPX in 80 non- atopic asthmatic children were
      compared with those in 25 healthy control children. The patients were studied
      during attacks and two weeks later. The severity of asthma attacks was determined
      according to a pre-existing score. U-EPX was measured by the specific
      radioimmunoassay technique (Pharmacia, Uppsala, Sweden). This measurement was
      correlated with the clinical and radiological investigations as well as with
      other variables such as blood oxygen saturation, peak expiratory rate and
      eosinophil count. RESULTS: U-EPX concentrations were significantly higher in all
      asthmatic children during attacks (139.6 11.7 microg/mmol of creatinine) than
      those in the control group (35.3 6.2 microg/mmol of creatinine) (p < 0.001). Two
      weeks after resolution of the exacerbation, U-EPX significantly decreased (66.5
      9.3 microg/mmol of creatinine) (p < 0.001). U-EPX concentrations were highest in
      patients with severe attacks (191.5 11.3 microg/mmol of creatinine) (p < 0.001).
      No statistically significant differences were found between mild (88.2 7.2
      microg/mmol of creatinine) and moderate attacks (119.6 8.5 microg/mmol of
      creatinine). At the two-week follow-up, U-EPX concentrations in patients with
      mild or moderate attacks was similar to those in controls but were persistently
      elevated in the subgroup with severe attacks (103.8 9.4 microg/mmol of
      creatinine) (p < 0.001). No significant correlation was found between U-EPX
      concentrations and blood oxygen saturation, peak expiratory rate or eosinophil
      count. CONCLUSION: A statistically significant correlation was found between U
      EPX concentrations and the severity of attacks in asthmatic children. This
      substance could be useful in quantifying bronchial inflammation. This result
      could further be used as a marker of severity of disease exacerbation and would
      not only facilitate early diagnosis and staging of inflammatory and allergic
      disorders but would also allow therapy and interventions to be monitored.

PMID- 12199968
TI  - Pollen and spores in the air of a hospital out-patient ward.
AB  - BACKGROUND: Aerobiological studies of interest to the allergy specialist are
      routinely carried out using information from outdoor traps. However, most of our
      time is spent indoors and it is often the content of this air that is responsible
      for allergic phenomena. MATERIAL AND METHODS: The air of a hospital outpatient
      ward was analyzed using two portable volumetric aerobiological traps, one at
      floor level and the other at a height of 1 meter. Both spores and pollen grains
      were counted and their values were compared with those outside the building.
      RESULTS AND CONCLUSIONS: Twenty types of pollen grains were found. Their
      concentrations ranged from 2.7 and 25.1 grains/m3, with the most frequent being
      (in order) grasses, evergreen oak (holm and cork oaks), water plantain, and
      olive. Twenty two different types of spores were found with concentrations of
      between 175.0 and 1395.8 spores/m3 and the most frequent were Cladosporium,
      Ustilago and basidiospores. No significant differences were found between the
      floor level and the meter-high measurements. Comparison with outdoor levels
      showed that the three most abundant pollen types were correlated, with a ratio of
      30:1 between indoor and outdoor levels. For the spores and fungi propagules, the
      indoor:outdoor ratio was highly variable, depending on the type. Thus, for
      Aspergillus-Penicillium spores, the concentration was even higher indoors than
      outdoors, although for most types, lower levels were found indoors, with a mean
      outdoor:indoor ratio of 4:1. We argue that this relationship reflects the
      presence of indoor spore sources. Rainfall was correlated with a decline in
      pollen levels and a rise in spore levels.

PMID- 12199969
TI  - Erythrodermia to pseudoephedrine in a patient with contact allergy to
      phenylephrine.
AB  - BACKGROUND: Phenylephrine and pseudoephedrine are sympathomimetic drugs belonging
      to the phenylamine family. Adverse cutaneous effects associated with these drugs
      have been reported but, in view of their frequent use, appear to be rare. The
      very close chemical structures of these drugs could explain potential cross
      reactions among them but the results reported in the literature are
      controversial. CASE REPORT: An 18-year-old woman developed blepharoconjunctivitis
      after application of phenylephrine and tropicamide eye drops. Four years after
      this reaction, she took 1 tablet of Narine (pseudoephedrine and loratadine) and 3
      4 hours later developed a generalized erythrodermic reaction. Cutaneous biopsy
      revealed hydropic changes in the basal layer and, in the dermis, moderate edema
      with slight perivascular lymphocyte and eosinophil infiltrates. Patch tests with
      European standard series, commercial eye drops, tropicamide, phenylephrine,
      pseudoephedrine and other sympathomimetic agents were applied to the patient's
      back. After 47 and 96 hours, only the patches with pseudoephedrine and
      phenylephrine were positive. CONCLUSIONS: We believe that our patient has
      presented two different reactions with different clinical outcome and
      histopathology, which are unlikely to be due to cross-reactivity between the
      drugs involved. We have found no similar coincidences reported int the
      literature.

PMID- 12199970
TI  - Anaphylaxis due to carrot as hidden food allergen.
AB  - Carrot is frequently involved in food allergies and oral allergy syndromes,
      usually in association with other foods. Nevertheless, carrot alone is rarely
      responsible for severe systemic reactions. We report a case of anaphylactic shock
      due to the inadvertent ingestion of carrot as a hidden allergen contained in an
      ice-cream. The etiological role of carrot in provoking the symptoms was
      thoroughly ascertained through appropriate in vivo and in vitro assays and by
      excluding, through double-blind placebo-controlled challenge, the involvement of
      other ingredients of the food. We highlight once again the harm and risks due to
      hidden food allergens contained in commercial preparations and the importance of
      thorough patient education and information.

PMID- 12199972
TI  - [Infective endocarditis: Are we managing our patients well?].

PMID- 12199971
TI  - Pressurised metered-dose inhalers (MDIs) versus dry powder inhalers devices
      (DPIs) to rapid-acting inhaled b2-agonists for asthma in children.
AB  - OBJECTIVE: To compare the clinical effectiveness of pressurized metered-dose
      inhalers (MDIs) with that of dry powder inhalers (DPIs) in delivering short
      acting b2-agonists in children with asthma. METHODS: Searches were performed in
      Medline (1997-March 2002), the Cochrane Library Database and the Embase reference
      lists of review articles and clinical trials. In addition, the international
      headquarters of b2-agonist manufacturers were contacted. We performed a review of
      randomized controlled trials. RESULTS: Ten randomized controlled trials were
      included. No differences in clinical effectiveness were found between MDIs and
      PDIs. Two studies reported that fewer adverse events occurred when the Turbuhaler
      was used. Two long-term studies in children found that children preferred the MDI
      to the Rotohaler. CONCLUSIONS: 1) In stable asthma, short-acting b2
      bronchodilators in standard MDIs are as effective as dry powder inhalers. 2)
      Pooling of results was limited by the small number of studies and therefore no
      overall conclusions could be drawn. 3) From the limited data available, we found
      little or no evidence for an additional clinical benefit of DPI devices over
      standard MDIs in children with asthma.

PMID- 12199973
TI  - [The registries of myocardial infarction: an opportunity for improvement. The
      PREVESE II Study].

PMID- 12199974
TI  - [Infectious endocarditis: degree of discordance between clinical guidelines
      recommendations and clinical practice].
AB  - INTRODUCTION AND OBJECTIVES: The present study was made to investigate the degree
      of discordance between the recommendations of clinical guidelines and actual
      practice in the care of patients with infectious endocarditis. MATERIAL AND
      METHODS: Data was gathered on 34 patients that were admitted to our hospital for
      native valve infection over a 4-year period. The degree of discordance (%) was
      obtained by comparing each clinical history with a catalog of 15 specific actions
      recommended in the clinical guidelines for four consecutive phases: pre
      diagnosis, hospital diagnosis, antibiotic treatment, and surgical treatment. A
      system was constructed, scoring each phase with the greatest detected error (on a
      severity scale of 0 to 8 points) and adding together the scores for the four
      phases. RESULTS: The mean degree of discordance was 30.5% (range, 0-66%). Scores
      of more than six points were clearly associated with an unfavourable evolution.
      CONCLUSIONS: The recommendations of clinical guidelines for infectious
      endocarditis are inadequately followed in practice, which can affect the course
      of the disease. It is necessary to increase adherence to clinical guidelines in
      practice, in order to improve the care of patients with this serious disease.

PMID- 12199975
TI  - [New data on secondary prevention of myocardial infarction in Spain. Results of
      the PREVESE II study].
AB  - Introduction and objectives. The PREVESE Study reported the situation of
      secondary prevention after myocardial infarction in Spain. Similar surveys
      conducted in Europe have also shown that the implementation of secondary
      prevention is not adequate. The aim of this second PREVESE study was to compare
      the situation in Spain four years after the first study.Patients and method. We
      included retrospectively 2,054 patients discharged after myocardial infarction
      from 74 Spanish hospitals. We studied the available information recorded in
      medical records after discharge, the prevalence of risk factors, procedures
      performed, and medical treatment before admission and at discharge. We compared
      the data collected with those from the first PREVESE study because the data
      collection methodology was similar.Results. The information recorded in the
      hospital medical records was satisfactory in relation to the most important risk
      factors (hypertension 94.8%; dyslipidemia and diabetes 97.9%; and smoking 89.2%).
      Compared with the previous study, there was a significant decrease in the
      percentage of smokers (46.1 vs. 35.4%). The echocardiogram was performed more
      frequently (60.1 vs. 85.6%) and there were also significant differences related
      to drug treatment at discharge, with an important increase in the prescription of
      beta-blockers (33.5 vs. 45.1%), ACE inhibitors (32.5 vs. 46.4%), and lipid
      lowering drugs (6.7 vs 30.5%).Conclusions. This study shows some improvement in
      the management of myocardial infarction patients after a four-year period, mainly
      due to more prescription of cardioprotective drugs at hospital discharge.

PMID- 12199976
TI  - [Does abciximab improve the prognosis of diabetics after percutaneous coronary
      intervention?].
AB  - INTRODUCTION AND OBJECTIVES: It is known that the outcome of percutaneous
      coronary intervention is worse in diabetics than in non-diabetics. The aim of our
      study was to determine whether abciximab therapy could improve clinical outcome
      in an unselected diabetic population that underwent percutaneous coronary
      interventions. MATERIAL AND METHODS: We analyzed retrospectively 198 diabetic
      patients who underwent PTCA from January 1997 to January 2000. Seventy-three
      patients (36.7%) were treated with abciximab and the remaining 125 patients
      (63.3%) did not receive abciximab. The mean follow-up was 12.6 months. The events
      considered were death, non-fatal myocardial infarction, any revascularization
      procedure (including the target vessel), and hospital admission for unstable
      angina. RESULTS: Patients who received abciximab had more frequent previous
      myocardial infarction (67.1 vs. 52.8%; p = 0.04), worse left ventricular function
      (0.53 vs. 0.59%; p = 0.02), more frequent angiographic thrombus (67.1 vs. 36.8%;
      p < 0.001), more complex lesions (B2/C) (76.4 vs. 55.8%; p = 0.004), and less
      frequent location in left anterior descending artery (34.2 vs. 60.8%; p = 0.002).
      The indication for PTCA in patients who received abciximab was most often related
      to myocardial infarction. There were no differences between the groups in sex,
      age and distribution of diabetes treatment. Events were more frequent in
      diabetics not treated with abciximab than in those who were treated with
      abciximab (38 vs. 22%; p < 0.037). The patients not treated with abciximab
      suffered more frequently target vessel revascularization (22.7 vs. 7.2%; p <
      0.007). There were no significant differences in the frequency of death or non
      fatal myocardial infarction, but hospital readmissions for unstable angina were
      significantly more frequent in diabetics not treated with abciximab (29.1 vs.
      15.9%; p = 0.045). Multivariate analysis identified abciximab as a predictor of
      the absence of complications during follow-up (OR: 0.45; p = 0.03). CONCLUSION:
      Abciximab treatment seems to reduce events in unselected diabetic patients
      undergoing percutaneous coronary intervention, particularly target vessel
      revascularization.

PMID- 12199977
TI  - [Prognostic value of persistent ST-segment elevation after successful primary
      angioplasty].
AB  - INTRODUCTION AND OBJECTIVES: A variable percentage of patients with myocardial
      infarction treated with successful primary angioplasty and restoration of
      coronary flow show persistent ST-segment elevation, probably due to inadequate
      cellular reperfusion. We studied if persistent ST-segment elevation was a
      predictor of worse prognosis. PATIENTS AND METHODS: We comparatively studied the
      clinical and angiographic results of 116 acute myocardial infarction patients
      after successful primary angioplasty, which were classified into two groups
      depending on the persistence (> 50%) or reduction (</= 50%) of ST-segment
      elevation between the electrocardiograms recorded before and after coronary
      angioplasty. RESULTS: In 96 patients (Group I) the ST-segment elevation improved
      after angioplasty and in 20 patients (Group II) there was no improvement.
      Baseline characteristics were similar in both groups except for Killip class 4,
      which was more prevalent in group II (7.2 vs. 25%; p = 0.01). There were no
      differences in the characteristics or results of the procedure. There was more
      myocardial damage in group II (CK 3,149 1,636 vs. 2,185 2,010 U/l; p = 0.02),
      associated with a more impaired left ventricular ejection fraction in the late
      angiographic control (47 16 vs 55 16%; p = 0.05). At a one-year follow-up the
      mortality was 8.3% in group I and 30% in group II (p = 0.01). CONCLUSIONS: The
      persistence of ST-segment elevation after successful primary angioplasty
      identifies a group of patients that may suffer an increased risk of adverse
      events in spite of good epicardial flow.

PMID- 12199978
TI  - [Short-term prognosis of patients admitted for probable acute coronary syndrome
      without ST-segment elevation. Role of new myocardial damage markers and acute
      phase reactants].
AB  - OBJECTIVES: The relative value of classic markers, myocardial damage variables,
      and levels of acute-phase reactants in establishing the pre-discharge prognosis
      of acute coronary syndrome without ST-segment elevation was analyzed. METHOD: We
      prospectively studied 385 consecutive patients admitted from our chest pain unit
      with a high-probability diagnosis of acute coronary syndrome without ST-segment
      elevation. The clinical and electrocardiographic data, myocardial damage markers
      (troponin I, CK-Mb mass, myoglobin), and acute-phase reactants (high-sensitivity
      C-reactive protein, fibrinogen) were recorded. RESULTS: During admission, 15
      deaths (3.9%) and 16 complicative infarctions (4.2%) occurred, for a total of 31
      major events (death and/or infarction: 8.1%). Age (p = 0.03), insulin-dependent
      diabetes (p = 0.009), and C-reactive protein (p = 0.05) were independently
      related to death. Fibrinogen was related to infarction (p = 0.01); by fibrinogen
      quartiles: 1.4%; 1.4%; 2.9%, and 11.7% (p = 0.02). Age (p = 0.01), insulin
      dependent diabetes (p = 0.02), and C-reactive protein (p = 0.04) were independent
      predictors of major events; by C-reactive protein quartiles: 1.4%; 5.5%; 5.4%,
      and 16.7% (p = 0.004). Troponin I was related to major events (p = 0.03), but it
      was not an independent predictor. CONCLUSIONS: Acute-phase reactants add
      independent information to clinical variables in the short-term risk
      stratification of patients with an acute coronary syndrome. The predictive power
      of troponins is lower than that of other variables.

PMID- 12199979
TI  - [Persistence of oxidative stress after heart transplantation: a comparative study
      of patients with heart transplant versus chronic stable heart failure].
AB  - INTRODUCTION AND OBJECTIVE: Chronic heart failure (CHF) is associated with
      oxidative stress. Heart transplantation, an important therapeutic alternative in
      these patients, could reduce oxidative stress by improving cardiac function. Our
      aim was to evaluate post-heart transplantation oxidative stress. PATIENTS AND
      METHOD: We studied three experimental groups: a) heart transplant recipients
      without evidence of rejection (n = 11); b) NYHA class III CHF patients (n = 19),
      and c) healthy control subjects (n = 14). Oxidative stress was assessed by
      measuring plasma malondialdehyde levels (MDA), and determining the enzymatic
      activities of glutathione peroxidase (GSH-Px), catalase (CAT), and superoxide
      dismutase (SOD). RESULTS: The demographic characteristics of the three groups
      were similar. Mean time from transplantation was 20.0 4.8 months. Mean MDA plasma
      levels in heart transplantation and CHF patients were significantly higher than
      in normal subjects (3.35 0.8; 3.27 1.7 y 0.9 0.3 microM, respectively). GSH-Px
      activity increased after transplantation compared to control subjects (0.40 0.06
      and 0.33 0.05 U/g Hb, respectively), but not the CHF group. A significant
      decrease in SOD activity was found in the heart transplant vs. CHF group (0.44
      0.1 vs. 0.87 0.6 U/mg Hb). There were no differences in CAT values between heart
      transplant and CHF patients. CONCLUSION: These findings demonstrated the presence
      of permanent oxidative stress in patients who have undergone heart
      transplantation, characterized by an increase in MDA and a decrease in SOD
      activity, despite an increase in GSH-Px activity.

PMID- 12199981
TI  - [Treatment of diabetes mellitus: general goals, and clinical practice
      management].
AB  - Diabetes mellitus is associated with a marked increased of cardiovascular events.
      The treatment strategy of diabetes has to be based on the knowledge of its
      pathophysiology. Thus, insulin is essential for treatment of type 1 diabetic
      patients because there is a defect in insulin secretion. However, treatment of
      type 2 diabetic patients is more complex because a defect in both insulin
      secretion and insulin action exists. Therefore, the treatment selection will
      depend on the stage of the disease and the individual characteristics of the
      patient. This article examines the general goals of the treatment and reviews the
      management of type 2 diabetes.

PMID- 12199980
TI  - [Effects of statins on angiogenesis and vasculogenesis].
AB  - Statins promote the proliferation, migration, and survival of endothelial cells
      and bone marrow-derived endothelial progenitor cells (angioblasts) by stimulating
      the serine/threonine protein kinase Akt (also known as protein kinase B) pathway.
      Like vascular endothelial growth factor (VEGF), the statins promote angiogenesis
      and vasculogenesis. Therefore, Akt activation may explain some of the beneficial
      effects of the statins, including postnatal neovascularization.

PMID- 12199982
TI  - [Purulent pericarditis with pneumopericardium caused by Streptococcus milleri].

PMID- 12199984
TI  - [Atrial hematoma in cardiac postoperative patients and the diagnostic use of
      transesophageal echocardiography].
AB  - The formation of atrial hematomas with a mass effect in patients who have
      undergone cardiac surgery originates a clinical and hemodynamic syndrome that is
      difficult to assess. Hypotension with high right atrial pressure and equalization
      of pulmonary wedge pressure is not always present due to the irregular
      distribution of the hematoma in cardiac chambers. Transesophageal
      echocardiography is a useful diagnostic procedure for atrial hematomas,
      differentiating them from other similar clinical and hemodynamic situations like
      left ventricular or prosthetic valve dysfunction. We present five clinical cases
      of patients who underwent cardiac surgery and presented atrial hematoma, right
      atrial in four and left atrial in one. All were diagnosed by transesophageal
      echocardiography. In one case magnetic resonance imaging was used.

PMID- 12199983
TI  - [Addition of an angiotensin II receptor blocker to maximal dose of ACE inhibitors
      in heart failure].
AB  - In heart failure, the benefits of adding angiotensin-receptor blockade to ACE
      inhibitors have been studied only with submaximal doses of ACE inhibitors. We
      included 20 patients (LVEF 24 7%, NYHA II-III), with no clinical or therapeutic
      variations in the previous three months, who were receiving maximal doses of ACE
      inhibitors. We added losartan 50 mg once a day. At six months, SBP decreased (115
      8 vs. 106 9 mmHg; p = 0.001), LVEF increased (24.4 7 vs. 34.1 7%; p < 0.001),
      ventricular end-diastolic volumes decreased (220 58 vs 190 46 ml; p = 0.007), and
      SPAP decreased (43 8 vs. 35 7 mmHg; p < 0.001). Seven patients improved one
      degree on the NYHA scale (p = 0.004), but VO2max did not change (20.8 5.2 vs.
      21.8 5.0 ml/kg/min, p = 0.120). Plasma levels of norepinephrine, at rest and
      maximal exercise, brain natriuretic peptide, and renin were similar. After
      maximum ACE inhibitor doses, the addition of losartan is safe and associated with
      an improvement in ventricular function and NYHA functional class, but with no
      change in neurohormonal status.

PMID- 12199985
TI  - [Diagnosis by magnetic resonance imaging of a case of intramural left atrial
      hematoma].
AB  - We report a case of spontaneous intramural left atrial hematoma with chest pain
      and pulmonary edema as the primary clinical manifestations. Echocardiographic
      techniques revealed obstruction of the left atrial cavity by cyst-like masses
      attached to the posterior and anterior atrial wall. A large intramural hematoma
      due to extensive atrial wall dissection was observed by magnetic resonance
      imaging. Surgery confirmed the diagnosis of intramural left atrial hematoma with
      no complications. We review the clinical and diagnostic profile of the three
      cases of spontaneous intramural left atrial hematoma reported in the world
      medical literature.

PMID- 12199986
TI  - [Acute myocardial failure in a young man: Q-fever myocarditis].
AB  - Coxiella burnetii myocarditis is a rare but severe clinical form of acute Q
      fever. We report the case of a 40-year-old man hospitalized for acute febrile
      syndrome. Forty-eight hours later, he presented dyspnea, orthopnea, and
      paroxysmal nocturnal dyspnea; cardiac auscultation revealed a third sound and
      echocardiography showed a diffusely hypokinetic and dilated left ventricle (30%
      ejection fraction). Serological studies showed antibodies against phase-II C.
      burnetii antigens (IgG titer 1:320 and IgM 1:50). The patient was treated with
      losartan, furosemide, and clarithromycin, resulting in rapid improvement. Six
      months after admission, the echocardiographic changes had completely disappeared.

PMID- 12199987
TI  - [Ventricular tachycardia and long QT associated with clarithromycin
      administration in a patient with HIV infection].
AB  - Prolongation of the QT interval is associated with a high risk of serious
      ventricular tachyarrhythmias, usually torsade de pointes (TdP) polymorphic
      ventricular tachycardia, although monomorphic ventricular tachycardia may also
      develop. Both congenital and acquired forms have been reported, acquired forms
      being much more prevalent. An association between human immunodeficiency virus
      (HIV) infection and a higher rate of dilated cardiomyopathy has also been
      recognized. The severity of immunodeficiency seems to influence both the
      incidence and severity of cardiomyopathy. A higher prevalence of QT prolongation
      has been reported among hospitalized HIV-positive patients with HIV infection,
      possibly related to drugs prescribed for such patients or to an acquired form of
      long QT syndrome arising from HIV infection. We report a case of QT prolongation
      and development of ventricular arrhythmia in one HIV patient that started with
      intravenous clarithromycin and cotrimoxazole therapy.

PMID- 12199988
TI  - [The Spanish Journal of Nuclear Medicine: from 1991 to 2000].
AB  - OBJECTIVE: To describe the articles published in "Revista Espanola de Medicina
      Nuclear" (REMN) from 1991 through 2000. MATERIAL AND METHODS: Five hundred and
      forty-two articles (originals, reviews, editorials, letters, clinical notes and
      images of interest) published in REMN during the past 10 years (1991-2000) were
      gathered. The following variables were assessed: topic, procedure, type of
      article, number of authors, Spanish region affiliation, country, number of pages
      and number of references. The results for the five year periods 1991-1995 and
      1996-2000 were also presented. RESULTS: Excluding the editorial contributions,
      the most dealt with topic was the osteoarticular system (14.9%), followed by the
      heart (14.2%), endocrinology (12.1%), gastroenterology (11.3%) and neurology
      (10,3%). One hundred and thirty articles were linked to oncology. Madrid (23.7%),
      Catalonia (22.5%), Andalucia (10.6%) and Aragon (10.1%) were the Spanish regions
      that made the most contributions. Conventional planar scintigraphic studies were
      the most used procedure (49.1%), followed by SPECT (16.6%). The countries that
      were represented most were Spain and Cuba, with 410 and 36 works, respectively.
      The global trend underwent little change in the above variables in the decade.
      The pages/paper index was 6.1 +/- 1.7 for original papers and 6.5 +/- 4.3 for
      reviews. The authors/paper index was 6.3 +/- 2.3 for original papers and 2.7 +/-
      2.1 for reviews. The references/paper index was 21.9 +/- 11.4 for original papers
      and 3+/- 1.1 39.6 for reviews. These three indexes increased in all sections
      between the periods 1991-1995 and 1996-2000. CONCLUSIONS: This survey shows
      subtle qualitative changes throughout the period analyzed. A quantitative
      increase in the scientific production in the REMN seems to exist. However, many
      factors must be considered in the final evaluation of these results and this
      remains beyond the scope of this descriptive work.

PMID- 12199989
TI  - [A matter of principles].

PMID- 12199990
TI  - [Prognostic factors of mortality during the episode of pneumonia due to
      Pneumocystis carinii in patients with HIV infection].
AB  - BACKGROUND: Despite a steady decrease in its incidence, pneumonia caused by
      Pneumocystis carinii (PCP) are still diagnosed, and they occur frequently in
      patients unaware of being infected with the human immunodeficiency virus (HIV).
      Since it is a disease with a high mortality risk, its early diagnosis and therapy
      would allow these patients to benefit from the advantages afforded Pneumocystis
      carinii, neumonia, infecciones oportunistas relacionadas con el sida,
      pronostico.by anti-retroviral therapy. PATIENTS AND METHODS: Retrospective study,
      in which all adult HIV infected patients with microbiologically demonstrated PCP
      diagnosed at two tertiary-level hospitals in our country between 1985 and 1996
      were included. The clinical records of patients were used as information source.
      The relative risks (RR) of death were estimated by the multivariant logistic
      regression. RESULTS: PCP was the first AIDS indicating disease in approximately
      70 % of cases. Thirteen percent of patients died during the episode. Patients
      aged over 45 years had a death RR during the episode of 3.15 (95 % CI from 0.8 to
      12.2); patients previously diagnosed of AIDS had a death RR of 3.4 (95 % CI from
      1.3 to 9), and those with an alveolar-arterial oxygen gradient (pA-aO2) > 50
      mmHg, a death RR of 3 (95% CI from 1.1 to 8). CONCLUSIONS: Factors independently
      related to survival to the PCP episode are age below 45 years, not to have had
      another AIDS indicating disease, and to have a pA-aO2 below 50 mmHg at diagnosis.

PMID- 12199991
TI  - [Prevalence of diabetes mellitus and glucose intolerance in the population aged
      30 to 75 years in Asturias, Spain].
AB  - OBJECTIVE: To know the prevalence of type 2 diabetes mellitus (DM2) and glucose
      intolerance (GIT) in the adult population in Asturias. METHODS: Population based,
      cross-sectional study. A total of 1,034 individuals (54,1%, women) aged 30-75
      years were randomly selected. Individuals responded to a questionnaire, underwent
      physical examination, and an oral glucose overload test; vein blood was extracted
      to determine both basal and 2-hour glucose levels. The diagnostic criteria set up
      by the World Health Organization in 1985 were used. RESULTS: The overall DM2
      prevalence was 9.9% (8.2% to 11.7%), known DM 4% (2.8% to 5.1%), unknown DM 5.9%
      (4.5% to 7.4%). The unknown diabetes/hnown diabetes ratio was 1.5/1. The
      prevalence of GIT was 13.3 % (11.3% to 15.2%). The prevalence of DM for the Segi
      population (30-64 years) was 8.2% among men and 5.2% among women. Factors
      independently associated with DM included age, increased blood pressure, family
      history of diabetes, obesity, and hypertriglyceridemia. CONCLUSION: The
      prevalence of DM2 in the adult population of Asturias (9.9%) is moderately high
      and similar to that observed in our country and other white populations in the
      world. More than half of patients with DM are unaware of their condition; thus,
      planning strategies for and early diagnosis would be helpful for the high risk
      populations.

PMID- 12199992
TI  - [Short-term and long-term evolution of deep vein thrombosis treated by a health
      care unit].
AB  - INTRODUCTION AND OBJECTIVES: Deep vein thrombosis (DVT) is a common disease, with
      a high risk of complications persisting for years. Until recently, the treatment
      of this condition was on an hospitalary basis. Nevertheless, there is growing
      evidence suggesting an adequate management on an ambulatory basis with low
      molecular weight heparin (LMWH). Based upon these observations, and observational
      study was performed to determine short-term ad long-term complications of DVT
      treated by a Home Care Unit (HCU). METHODS: A total of 125 patients diagnosed of
      DVT by means of Doppler echography were treated on an ambulatory basis with
      subcutaneous nadroparine followed by oral anticoagulants (OAC) or LMWH alone,
      when a contraindication for acenocumarol use was present. The characteristics of
      the study population and their risk factors were studied, as well as the presence
      of bleeding or relapse during the acute period. Once the acute period with
      surveillance and treatment by the DHU was over, patients were followed at the
      Outpatient Clinics of the Internal Medicine Department. At each visit, the long
      term complications were assessed: relapse, postflebitis syndrome (PFS), or death.
      RESULTS: The most common short-term complications were bleeding (3.2%) and
      relapse (7.3%). Eighteen percent of patients showed liver toxicity (increase of
      at least a 1.5 fold in the basal values of transaminases) secondary to the use of
      nadroparine. Nevertheless, this toxicity was mild in all cases and subsided when
      the medication was stopped. With a mean follow-up of 15.4 months, an overall
      16.5% of patients relapsed, 25.8 % of patients had a PFS, and 23.7% of patients
      died. Death was associated with the presence of some risk factors (32.7% versus
      7.69%; p = 0.004), and particularly when this risk factor was a tumor (75% versus
      12%; p < 0.001). CONCLUSIONS: Deep vein thrombosis is a condition associated with
      common complications, both in the acute period and in the long-term.
      Nevertheless, it can be treated safely and efficiently by a HCU. This disease is
      associated with a high risk of mortality, particularly because it is usually
      associated with severe diseases.

PMID- 12199994
TI  - [Asthma in the elderly].

PMID- 12199993
TI  - [Naltrexone use in the treatment of alcoholism in Spain].
AB  - To analyse the causes that prompted health care professionals to select
      naltrexone to treat alcoholism. One-year multicentric, prospective study
      conducted with 221 doctors specialized in alcoholism treatment and analysis of
      data derived from 1,396 patients attended. Naltrexone was not prescribed to 446
      patients. The medical barriers to the prescription of naltrexone included the
      mode of understanding alcoholism by doctors (20 % of doctors), patients
      reluctance to take naltrexone (26.9 % of patients), the presence of a concomitant
      condition (27.6 %) and barriers associated with health care system (6 % of
      patients). The logistic regression model explained why doctors tended not to
      prescribe naltrexone when patients had a long course of their disease or had
      previously received acamprosate.

PMID- 12199995
TI  - [Current strategies for the diagnosis and treatment of patients with sialorrhea].

PMID- 12199996
TI  - [Indications for laparoscopic surgery].

PMID- 12199997
TI  - [Medical professionalism in the new millennium: a medical statute].

PMID- 12199998
TI  - [Abdominal pain and fever in a 36-year old woman with a cystic tumor in the right
      abdomen].

PMID- 12199999
TI  - [Abdominal pain and flanck mass].

PMID- 12200000
TI  - [Acute back pain in a 74 year old woman].

PMID- 12200001
TI  - [Cerebral infarction of rare etiology in a young patient].

PMID- 12200002
TI  - [Relapse of a non-Hodgkin lymphoma in a central vein reservoir port-a-cath type].

PMID- 12200003
TI  - [C677TT mutation in methylentetrahydrofolate reductase, homocysteine and
      thrombophilia].

PMID- 12200004
TI  - [An exceptional presentation of SLE].

PMID- 12200005
TI  - [Involvement of pharmacoeconomic criteria for obtaining high-quality medical
      care].

PMID- 12200006
TI  - [Genotypic resistance of human immunodeficiency virus in patients with virologic
      failure].
AB  - BACKGROUND: The aim of the present study is to asses the prevalence of
      resistances in a group of patients with virological failure establishing the
      relationship between the appearance of mutations and the given antiretroviral
      therapy along with other variables used in these patients follow-up. PATIENTS AND
      METHOD: Samples belonging to 88 patients were selected either with viral load
      levels above 30.000 copies/ml after reaching undetectable viral load levels, or
      with persistently detectable levels above 1.000 copies/ml. Resistances were
      tested by means of Line Probe Assay (LiPA). The history of patients'
      antiretroviral treatments was reviewed. RESULTS: Mutations were observed in 52,6%
      of cases for reverse transcriptase (RT) an in 81,8% for the protease genes, being
      T215Y and V82A the most frequently detected ones. Mutations coferring resistance
      to the given antiretrovirals appeared in 33 cases. No statistical significance
      was observed between the presence of mutations and the administered therapy. In
      the multivariate analysis we found for LiPA RT a greater risk of appearance of
      mutations according to patient motility (OR = 4,0). CONCLUSIONS: the prevalence
      of resistance mutations in patients with virologic failure is placed around 50%
      in both genes. A consensus in the definition of virologic failure in HIV infected
      patients is urged.

PMID- 12200007
TI  - [Lung cancer and vegetable consumption in Asturias, Spain. A case control study].
AB  - BACKGROUND: Lung cancer in Asturias (Northern Spain) exceeds the Spanish average
      by 1.4 times. While the proportion of smokers is similar, consumption of
      vegetables is the lowest of Spain. The objective of the study was to examine the
      relationship between lung cancer and vegetable consumption in Asturias. PATIENTS
      AND METHOD: This was an incident, hospital-based, case-control study. Cases were
      newly diagnosed lung cancer patients and controls were patients from surgical
      wards. Diet habits were obtained by means of a food frequency questionnaire with
      one year recall time. Information was also sought on smoking, occupational
      exposure and demographic variables. RESULTS: 197 cases and 196 controls were
      included in the study. Those at the 80th percentile of cruciferous (e.g, cabbage,
      broccoli) consumption had half the risk of lung cancer, other than
      adenocarcinoma, as compared to those at the 20th percentile [OR = 0.47; 95% CI,
      0.23-0.95 in the crude analysis]. However, when adjusting for smoking and social
      class, the association was no longer significant, possibly due to a low power of
      the study. A high vegetable, vitamin A or betacarotene consumption was not
      associated with a lower risk of lung cancer. CONCLUSIONS: This study points
      towards a protective effect of cruciferous vegetables in lung cancer, other than
      adenocarcinoma. However, even in the case such a vegetable were protective, it
      could not explain by itself the existing differences in lung cancer rates between
      Asturias and the the rest of Spain.

PMID- 12200008
TI  - [Susceptibility to antifungal agents of Cryptococcus species of clinical
      interest].
AB  - BACKGROUND: Studies on the susceptability of Cryptococcus species to antifungal
      agents are scarce. METHOD: We investigate the susceptibility of 54 clinical and
      environmental strains from six different species using the Sensititre and the
      NCCLS methods. RESULTS: Environmental strains were less susceptible than clinical
      strains. We found MICs >= 64 mg/l for fluconazole, MICs >= 1 mg/l for
      itraconazole and MICs >= 32 mg/l for 5-fluorocytosine in C. albidus, C.
      neoformans and C. uniguttulatus. CONCLUSIONS: These findings point at the
      importance of determining the antifungal susceptibility of Cryptococcus species.

PMID- 12200009
TI  - [Clinical applications of erythropoietin: Impact on blood transfusion].

PMID- 12200010
TI  - [Prevalence of Helicobacter pylori infection in gastroesophageal reflux disease
      and Barretts esophagus].

PMID- 12200011
TI  - [Pharmacokinetic interactions between methadone and antiretroviral medication in
      HIV positive patients].

PMID- 12200012
TI  - [Multivariate models in biomedical research: criteria for the inclusion of
      variables].

PMID- 12200013
TI  - [Caracteristicas clinicoepidemiologicas de los pacientes recien diagnosticados de
      infeccion por el virus de la inmunodeficiencia humana].

PMID- 12200015
TI  - [mm Hg versus mmHg].

PMID- 12200016
TI  - [Atherosclerosis and anti-oxidized low density lipoprotein antibodies in an
      elderly population].
AB  - BACKGROUND: Antibodies to oxidized LDL (anti-OxLDL) have been found to be
      associated with atherosclerosis. The aim of the study was to evaluate the
      relationship between anti-OxLDL antibodies and atherosclerosis in the elderly.
      PATIENTS AND METHOD: We studied several risk factors and different clinical
      manifestations of atherosclerosis in 100 people older than 65 years and in 48
      healthy blood donor controls (age range: 20 to 55 years). Anti-OxLDL antibodies
      were measured by ELISA. RESULTS: Thirty-one percent of the patients tested
      positive for anti-OxLDL. This percentage increased in the group of subjects
      without any risk factor or clinical manifestation (66.6%) as it was the case of
      the mean optical density (O.D.) value (O.D. = 0.671 vs. 0.357 in our general
      geriatric population). Most of those with a proven atherosclerotic event tested
      negative for anti-OxLDL antibodies and a statistically significant difference was
      shown for those with a calcified aortic arch (P = 0.041, 95% CI 0.15-0.97). Mean
      value of risk factors and clinical manifestations was 3.50 among anti-OxLDL
      negative patients, whereas it was 2.51 in the anti-OxLDL-positive group (P =
      0.035, 95% CI 0.07-1.91). Actually, when more adverse effects were present,
      patients' trend to test negative for anti-OxLDL antibodies was higher. An inverse
      correlation was observed between anti-OxLDL titers and the relative risk of
      coronary heart disease (P = 0.020). CONCLUSIONS: The cause of the decrease of
      free anti-OxLDL antibodies in situations that lead to an oxidative stress is
      unknown but it may be explained by the formation of immunocomplexes in an effort
      to ease the clearance of oxidized substrates.

PMID- 12200017
TI  - [Megestrol acetate: a systematic review usefulness about the weight gain in
      neoplastic patients with cachexia].
AB  - BACKGROUND: The clinical efficacy of megestrol acetate in the treatment of
      cachexia in cancer patients has not been clearly demonstrated. A systematic
      review and meta-analysis have been performed to ascertain its effectiveness on
      weight gain in patients with cancer-associated cachexia. MATERIAL AND METHOD: A
      systematic review of randomized clinical trials comparing megestrol acetate with
      placebo in cancer patients was performed. The outcome measure used was weight
      gain expressed as the difference in weight at the outset compared with that at
      the end of treatment. Trials analyzed were those that allowed for this
      calculation, or those whose authors provided information for the above
      calculation. RESULTS: Patients treated with placebo had an average weight loss of
      1.090 kg (CI 95%, 1.620 to 0.561), whereas patients treated with megestrol
      acetate gained an average 0.423 kg (CI 95%, 0.078-0.769). A weight gain of 0.448
      kg (CI 95%, 0.021-0.874) was observed with acetate megestrol doses # 240 mg. No
      statistically significant effect was observed when using higher doses: 0.358 kg
      (CI 95%, 0.135-0.85). CONCLUSIONS: Megestrol acetate doses equal to or lower than
      240 mg/day lead to slight weight gain in patients with cancer-associated
      cachexia. The majority of studies have a low methodological quality. Further,
      well-designed studies comparing megestrol acetate with placebo are warranted.

PMID- 12200018
TI  - [Varicella and parvovirus B19 immunity among pregnant women in Gijon, Spain].
AB  - BACKGROUND: We aimed at determining the inmunological status regarding varicella
      and parvovirus B19 in pregnant women in Gijon, Spain, and its correlation with
      several clinical and epidemiological parameters. PATIENTS AND METHOD: Blood
      samples taken during the first trimester of pregnancy in the area of Gijon were
      analysed to determine the immunological status with respect to varicella and
      parvovirus B19. The study included 2 groups: 99 non-European (all tested for both
      varicella and parvovirus) and 2,188 Europeans (406 were randomly selected for
      varicella test and 287 for parvovirus test). All patients underwent a clinical
      epidemiological survey. RESULTS: With regard to varicella, while 89% of pregnant
      women aged 14 to 35 years displayed immunity, this percentage reached 100% in
      those older than 35 years. Sensitivity was 73.8%, specificity 74.4%, positive
      predictive value 96.6% and negative predictive value was 22.6%. As for parvovirus
      B19, immunity was observed in 59.9% of Europeans and 67.7% of non-Europeans,
      without significant differences in the analysed parameters. CONCLUSIONS:
      Susceptibility to infection by varicella among pregnant women younger than 36
      years reaches 10% in Gijon. Clinical surveys are useful to avoid a pre
      vaccination serological study in an already immune population. Just over one
      third of these pregnant women are susceptible to infection by parvovirus B19.

PMID- 12200019
TI  - [About Stockholm syndrome].

PMID- 12200020
TI  - [The model of biopsychosocial evolution].

PMID- 12200021
TI  - [Diet and cardiovascular disease].

PMID- 12200023
TI  - [Reactive arthritis following Mycoplasma pneumoniae infection].

PMID- 12200022
TI  - [Arthralgia and interstitial neuropathy in a 44-year-old woman].

PMID- 12200024
TI  - [Ca-125 as a tumor marker in a patient with non Hodgkins lymphoma].

PMID- 12200025
TI  - [Descending necrotizing mediastinitis: an unfrequent life-threatening
      complication].

PMID- 12200026
TI  - [Focal and diffuse nesidioblastosis].

PMID- 12200028
TI  - Age-associated biomarker profiles of human breast cancer.
AB  - To explore the hypothesis that aging not only increases breast cancer incidence
      but also alters breast cancer biology, we correlated patient age and diagnosis
      with tumor histology, stage and biomarkers independently determined from two
      different tumor archives: an American collection of approximately 800 paraffin
      embedded and immunohistochemically analyzed primary breast cancers, and an
      European collection of approximately 3000 cryobanked primary breast cancers
      analyzed by ligand-binding and enzyme immunoassay (EIA). The prognostic
      biomarkers chosen for comparison represented surrogate measures of tumor: (i).
      proliferation, growth and genetic instability (mitotic and apoptotic indices, Ki
      67/MIB-1-positivity, nuclear grade, p53-positivity), (ii). endocrine-dependence
      (estrogen receptor (ER), progesterone receptors (PR), pS2, Bcl2), (iii). growth
      factor receptor-dependence (ErbB2, EGFR/ErbB1), and (iv). angiogenic, invasive
      and proteolytic potential (uPA, PAI-1, Cathepsin D, VEGF). No biomarker
      reflecting tumor angiogenic, invasive or proteolytic potential showed a
      significant correlation with patient age at diagnosis. In contrast, significant
      inverse correlations (|r|>0.1; P< or =0.05) were observed for all measures of
      tumor growth and genetic instability as well as growth factor receptor
      overexpression (ErbB2 or EGFR positivity). Only one marker of endocrine
      dependence, ER expression, showed a significant positive correlation with patient
      age at diagnosis. In summary, these findings support the hypothesis that breast
      cancer biology is significantly affected by patient age. In particular, breast
      tumors arising in older patients have slower growth rates, are more likely to be
      ER-positive, and are less likely to be p53-positive, EGFR-positive or ErbB2
      positive.

PMID- 12200029
TI  - UVB-induced premature senescence of human diploid skin fibroblasts.
AB  - In this work, we show that repeated stresses with UVB (290-320 nm) induce stress
      induced premature senescence (SIPS) of skin human diploid fibroblasts (HDFs).
      HDFs at early cumulative population doublings were exposed three or five times to
      increasing subcytotoxic doses of UVB with one stress per day. After 2 days of
      recovery, several biomarkers of replicative senescence were established. First,
      there was an increase in the proportion of cells positive for senescence
      associated beta-galactosidase activity. Second, there was a loss of replicative
      potential as assessed by a very low level of [3H]-thymidine incorporation. Third,
      the steady-state level of the mRNA of three senescence-associated genes, i.e.
      fibronectin, osteonectin and SM22, was increased in HDFs at 72 h after three and
      five exposures to UVB. In conclusion, these results suggest that it is possible
      to induce SIPS in HDFs after repeated exposures to subcytotoxic doses of UVB.
      This model could be used to test whether HDFs in UVB-induced premature senescence
      are able to promote epithelial cell growth and tumorigenesis in skin, as shown
      recently with HDFs in H(2)O(2)-induced premature senescence.

PMID- 12200030
TI  - Molecular mechanisms linking calorie restriction and longevity.
AB  - Calorie-restricted feeding retards the rate of ageing in mammalian and
      invertebrate species. The molecular mechanisms underlying this effect include a
      lower rate of accrual of tissue oxidative damage that is associated with a
      significantly lower rate of mitochondrial free radical generation in rodent
      species. To identify the important sites of control and regulation for
      mitochondrial free radical generation during ageing and calorie-restricted
      feeding, metabolic control analysis is being applied to the study of
      mitochondrial bioenergetics. With ageing an increase in the mitochondrial proton
      leak is observed in mouse hepatocytes and in rat skeletal muscle. Limited data
      suggest that calorie-restricted feeding lowers the inner mitochondrial membrane
      potential and this may explain the reduced rate of free radical generation. A
      lowered unsaturation/saturation index is observed for mitochondrial membrane
      lipids in calorie-restricted rodents resulting in an altered membrane structure
      and function. Plasma concentrations of insulin and triiodothyronine are
      significantly lower under calorie-restricted feeding conditions and these
      hormones exert transcriptional control over desaturase enzymes that are important
      in the control of membrane lipid unsaturation. A loss of double bonds should make
      the mitochondrial membranes more resistant to peroxidation damage and would also
      reduce the proton conductance of the membrane, raising the membrane potential at
      a given respiration rate. This effect however, appears to be offset by other
      membrane changes that may include increased activity of uncoupling proteins.
      These unidentified adaptations increase the proton leak in calorie-restricted
      animals resulting in a lowering of the membrane potential and ROS generation.

PMID- 12200031
TI  - Copper homeostasis and aging in the fungal model system Podospora anserina:
      differential expression of PaCtr3 encoding a copper transporter.
AB  - Lifespan extension of Podospora anserina mutant grisea is caused by a loss-of
      function mutation in the nuclear gene Grisea. This gene encodes the copper
      regulated transcription factor GRISEA recently shown to be involved in the
      expression of PaSod2 encoding the mitochondrial manganese superoxide dismutase.
      Here we report the identification and characterization of a second target gene.
      This gene, PaCtr3, encodes a functional homologue of the Saccharomyces cerevisiae
      high affinity copper permease yCTR3. PaCtr3 is not expressed in the grisea mutant
      confirming the assumption that the extension of lifespan is primarily caused by
      cellular copper limitation and a switch from a cytochrome oxidase (COX)-dependent
      to and alternative oxidase (AOX)-dependent respiration. Transcript levels of
      PaCtr3 and PaSod2 respond to copper, iron, manganese and zinc. Transcription of
      PaCtr3 was found to be down-regulated during senescence of wild-type cultures
      suggesting that the intracellular copper concentration is raised in old cultures.
      A two hybrid analysis suggested that GRISEA acts as a homodimer. In accordance,
      an inverted repeat was identified as a putative binding sequence in the promoter
      region of PaCtr3 and of PaSod2. Finally, the expression of PaCtr3 in
      transformants of the grisea mutant led to lifespan shortening. This effect
      correlates with the activity of the copper-dependent COX demonstrating a strong
      link between copper-uptake, respiration and lifespan.

PMID- 12200032
TI  - Mitochondrial function and dysfunction in the cell: its relevance to aging and
      aging-related disease.
AB  - Mitochondria plays a complex multi-factorial role in the cell. In addition to
      their primary role in ATP generation, the organelles sequester calcium and both
      generate and detoxify reactive oxygen species. All these functions are intimately
      inter-linked through the central bioenergetic parameter of the proton
      electrochemical gradient across the inner mitochondrial membrane. Subtle changes
      in respiratory chain capacity, substrate supply, glutathione levels, cytoplasmic
      calcium and membrane potential occur in aging and in conditions predisposing
      towards neurodegenerative disease. These interactions are incompletely understood
      and in this review I present an overview of some of the current research in this
      area, and its possible relevance to aging and aging-related disease.

PMID- 12200033
TI  - Molecular changes accompanying senescence and immortalization of cultured human
      mammary epithelial cells.
AB  - Limits on the proliferative potential of cultured normal human cells may be
      consequences of pathways that exist to suppress tumorigenicity. Human mammary
      epithelial cells (HMEC) employ several mechanisms to prevent unlimited growth.
      One mechanism may be activated by stress, and is associated with upregulated
      expression of p16(INK4a). In serum-free medium, some HMEC arise spontaneously
      which do not express p16. These "post-selection" HMEC are capable of long-term
      proliferation, but ultimately cease growth when their telomeres become very
      short. As they approach a growth plateau, termed agonescence, post-selection HMEC
      populations accumulate chromosome abnormalities. In contrast to the crisis
      exhibited by cells lacking functional p53, agonescent cells can be maintained as
      viable cultures. Although transduction of hTERT, the catalytic subunit of
      telomerase, into post-selection cells can, by itself, efficiently produce
      immortality and avoid agonescence, the errors that produce telomerase
      reactivation during carcinogenesis are not known. The block to endogenous
      telomerase reactivation in HMEC is extremely stringent. However, if one
      predisposing error is present, the probability greatly increases that additional
      error(s) required for immortalization may be generated by genomic instability
      encountered during agonescence. In p53(+) HMEC immortalized after chemical
      carcinogen exposure, the events involved in overcoming agonescence can be
      temporally separated from activation of telomerase. We have used the term
      "conversion" to describe the gradual process that leads to telomerase activation,
      telomere length stabilization, decreased p57 (KIP2) expression, and increased
      ability to grow uniformly well in the presence or absence of TGF beta. In the
      presence of active p53, conversion may represent a rate-limiting step in immortal
      transformation.

PMID- 12200034
TI  - Animal models of oxidative stress, aging, and therapeutic antioxidant
      interventions.
AB  - Oxidative stress is a ubiquitous phenomena in all cell types, and it is primarily
      produced in mitochondria which are essential for multicellular life. Oxidative
      stress targets can be wide ranging and include nucleic acids and a variety of
      macromolecules. This review discusses the role of oxidative stress in the context
      of animal models, focusing in particular on animal models of aging, as well as
      the development of a new class of therapeutic small molecular weight antioxidants
      that have proven effective in extending the lifespan of a simple invertebrate
      nematode.

PMID- 12200035
TI  - Cancer and aging: a model for the cancer promoting effects of the aging stroma.
AB  - The incidence of cancer rises exponentially with age in humans and many other
      mammalian species. Malignant tumors are caused by an accumulation of oncogenic
      mutations. In addition, malignant tumorigenesis requires a permissive tissue
      environment in which mutant cells can survive, proliferate, and express their
      neoplastic phenotype. We propose that the age-related increase in cancer results
      from a synergy between the accumulation of mutations and age-related, pro
      oncogenic changes in the tissue milieu. Most age-related cancers derive from the
      epithelial cells of renewable tissues. An important element of epithelial tissues
      is the stroma, the sub-epithelial layer composed of extracellular matrix and
      several cell types. The stroma is maintained, remodeled and repaired by resident
      fibroblasts, supports and instructs the epithelium, and is essential for
      epithelial function. One change that occurs in tissues during aging is the
      accumulation of epithelial cells and fibroblasts that have undergone cellular
      senescence. Cellular senescence irreversibly arrests proliferation in response to
      damage or stimuli that put cells at risk for neoplastic transformation. Senescent
      cells secrete factors that can disrupt tissue architecture and/or stimulate
      nearby cells to proliferate. We therefore speculate that their presence may
      create a pro-oncogenic tissue environment that synergizes with oncogenic
      mutations to drive the rise in cancer incidence with age. Recent evidence lends
      support to this idea, and suggests that senescent stromal fibroblasts may be
      particularly adept at creating a tissue environment that can promote the
      development of age-related epithelial cancers.

PMID- 12200036
TI  - From the Hayflick mosaic to the mosaics of ageing. Role of stress-induced
      premature senescence in human ageing.
AB  - The Hayflick limit-senescence of proliferative cell types-is a fundamental
      feature of proliferative cells in vitro. Various human proliferative cell types
      exposed in vitro to many types of subcytotoxic stresses undergo stress-induced
      premature senescence (SIPS) (also called stress-induced premature senescence-like
      phenotype, according to the definition of senescence). The known mechanisms of
      appearance the main features of SIPS are reviewed: senescent-like morphology,
      growth arrest, senescence-related changes in gene expression, telomere
      shortening. Long before telomere-shortening induces senescence, other factors
      such as culture conditions or lack of 'feeder cells' can trigger either SIPS or
      prolonged reversible G(0) phase of the cell cycle. In vivo, 'proliferative' cell
      types of aged individuals are likely to compose a mosaic made of cells
      irreversibly growth arrested or not. The higher level of stress to which these
      cells have been exposed throughout their life span, the higher proportion of the
      cells of this mosaic will be in SIPS rather than in telomere-shortening dependent
      senescence. All cell types undergoing SIPS in vivo, most notably the ones in
      stressful conditions, are likely to participate in the tissular changes observed
      along ageing. For instance, human diploid fibroblasts (HDFs) exposed in vivo and
      in vitro to pro-inflammatory cytokines display biomarkers of senescence and might
      participate in the degradation of the extracellular matrix observed in ageing.

PMID- 12200037
TI  - Clusterin/apolipoprotein J in human aging and cancer.
AB  - Clusterin/Apolipoprotein J (ApoJ) is a heterodimeric highly conserved secreted
      glycoprotein being expressed in a wide variety of tissues and found in all human
      fluids. Despite being cloned since 1989, no genuine function has been attributed
      to ApoJ so far. The protein has been reportedly implicated in several diverse
      physiological processes such as sperm maturation, lipid transportation,
      complement inhibition, tissue remodeling, membrane recycling, cell-cell and cell
      substratum interactions, stabilization of stressed proteins in a folding
      competent state and promotion or inhibition of apoptosis. ApoJ gene is
      differentially regulated by cytokines, growth factors and stress-inducing agents,
      while another defining prominent and intriguing ApoJ feature is its upregulation
      in many severe physiological disturbances states and in several neurodegenerative
      conditions mostly related to advanced aging. Moreover, ApoJ accumulates during
      the viable growth arrested cellular state of senescence, that is thought to
      contribute to aging and to tumorigenesis suppression; paradoxically ApoJ is also
      upregulated in several cases of in vivo cancer progression and tumor formation.
      This review focuses on the reported data related to ApoJ cell-type and signal
      specific regulation, function and site of action in normal and cancer cells. We
      discuss the role of ApoJ during cellular senescence and tumorigenesis, especially
      under the light of the recently demonstrated various ApoJ intracellular protein
      forms and their interaction with molecules involved in signal transduction and
      DNA repair, raising the possibility that its overexpression during cellular
      senescence might cause a predisposition to cancer.

PMID- 12200038
TI  - The variability of the mitochondrial genome in human aging: a key for life and
      death?
AB  - The impressive performance of the research in mitochondrial genetics and human
      aging in the last decade outlines a new scenery in which the inherited variation
      of the mitochondrial genome (mtDNA) may play a role in rate and quality of aging.
      This variation in humans was initially looked at as nearly neutral, and useful
      just for the reconstruction of human population history. However, recent data
      suggest that different mtDNA molecules are qualitatively different from each
      other. The aim of this paper is to discuss current ideas on the relationships
      among mitochondrial function, mtDNA inherited variation, and aging. The main
      processes where the mitochondrion is involved and the importance these processes
      have on aging and death of individuals will be described. A possible connection
      between programmed death phenomena (mitoptosis, apoptosis, phenoptosis) and rate
      and quality of aging will be discussed. Finally, the possible role played in
      these processes by the mtDNA germline variation will be explored.

PMID- 12200039
TI  - Impairment of proteasome structure and function in aging.
AB  - Damage to macromolecules, and in particular protein, implicated in the cellular
      degeneration that occurs during the aging process, is corroborated by the
      accumulation of oxidative end-products over time. Oxidized protein build up is
      commonly seen as a hallmark of cellular aging. Protein turnover is essential to
      preserve cell function and the main proteolytic system in charge of cytosolic
      protein degradation is the proteasome. The proteasome is a multi-catalytic
      proteolytic complex, which recognizes and selectively degrades oxidatively
      damaged and ubiquitinated proteins. One of the hypothesis put forward to explain
      the accumulation of altered proteins is the decrease of proteasome activity with
      age. Indeed, accumulation of altered protein can be explained by increased
      protein alteration, decreased protein degradation or the combination of both. A
      short description of proteasome structure and of its role in cellular functions
      is first given. Then, accumulation of damaged protein is presented with emphasis
      on the pathways implicated in the formation of altered proteins. Finally,
      evidence for an age-related impairment of proteasome structure and function that
      has been reported by different groups is provided in the light of proteasomal
      dysfunction induced upon oxidative stress. It is now clear that proteasome
      activity is declining with age and that the loss in proteasome activity during
      aging is dependent of at least three different mechanisms: decreased proteasome
      expression; alterations and/or replacement of proteasome subunits and formation
      of inhibitory cross-linked proteins. However, it is also clear that events
      leading to the age- and disease-related loss of proteasome function have not yet
      been fully characterized.

PMID- 12200040
TI  - Senescence and epigenetic dysregulation in cancer.
AB  - Mammalian cells have a finite proliferative lifespan, at the end of which they
      are unable to enter S phase in response to mitogenic stimuli. They undergo
      morphological changes and synthesize an altered repertoire of cell type-specific
      proteins. This non-proliferative state is termed replicative senescence and is
      regarded as a major tumor suppressor mechanism. The ability to overcome
      senescence and obtain a limitless replicative potential is called
      immortalization, and considered to be one of the prerequisites of cancer
      formation. While senescence mainly represents a genetically governed process,
      epigenetic changes in cancer have received increasing attention as an alternative
      mechanism for mediating gene expression changes in transformed cells. DNA
      methylation of promoter-containing CpG islands has emerged as an epigenetic
      mechanism of silencing tumor suppressor genes. New insights are being gained into
      the mechanisms causing aberrant methylation in cancer and evidence suggests that
      aging is accompanied by accumulation of cells with aberrant CpG island
      methylation. Aberrant methylation may contribute to many of the physiological and
      pathological changes associated with aging including tumor development. Finally,
      we describe how genes involved in promoting longevity might inhibit pathways
      promoting tumorigenesis.

PMID- 12200041
TI  - LAG1 puts the focus on ceramide signaling.
AB  - Longevity-assurance gene 1 (LAG 1) is a yeast longevity gene. Homologues of the
      Lag 1 protein can be found throughout phylogeny, although sequence similarity is
      very limited. The Lag 1 protein is located in the endoplasmic reticulum (ER),
      where it helps to accelerate the transport of glycosylphosphatidylinositol (GPI)
      anchored proteins to the Golgi. This function of Lag 1 p results from its
      participation in ceramide synthesis. Thus, Lag 1 p and its homologues are likely
      to play a role in ceramide signaling, which affects growth, proliferation, stress
      resistance, and apoptosis. This provides a wide range of physiologic processes
      through which Lag 1 p may impinge upon life span.

PMID- 12200042
TI  - Premature aging in RecQ helicase-deficient human syndromes.
AB  - The RecQ family of DNA helicases have potential roles in DNA repair, replication
      and/or recombination pathways. In humans, a defect in the RecQ family helicases
      encoded by the BLM, WRN and RECQ4 genes gives rise to Bloom's (BS), Werner's (WS)
      and Rothmund-Thomson (RTS) syndromes, respectively. These disorders are
      associated with cancer predisposition and/or premature aging. In Bloom's
      syndrome, affected individuals are predisposed to many types of cancer at an
      early age. Werner's syndrome is a premature aging disorder with a complex
      phenotype, which includes many age-related disorders that develop from puberty,
      including greying and thinning of the hair, bilateral cataract formation, type II
      diabetes mellitus, osteoporosis and atherosclerosis. The phenotype of Rothmund
      Thomson syndrome patients also consists of some features associated with
      premature aging, as well as predispositon to certain cancers. Here, we discuss
      the molecular basis of these RecQ helicase-deficient disorders.

PMID- 12200043
TI  - +1 Proteins and aging.
AB  - Molecular misreading is an expression used to describe errors in RNA that lead to
      the translation of mutated proteins. We have shown that dinucleotide deletions
      (delta GA, delta GU) are introduced in simple sequence repeats (e.g. GAGAG) of
      mRNA. If the resulting mutant transcripts escape RNA quality control systems,
      they are translated into +1 proteins. If functional domains are located
      downstream of the frameshift site, the result will be a protein with either a
      partial or complete loss of function. A clear example is ubiquitin(+1) (UBB(+1)),
      which has lost its capacity to ubiquitinate, i.e. tagging proteins destined for
      proteasomal degradation. This is an important step in regulating the degradation
      of misfolded proteins and transcription factors. In fact, UBB(+1) seems to block
      the proteasome. UBB(+1) and other proteins accumulate in the neuropathological
      hallmarks of Alzheimer's disease (AD), which suggests a causal relationship. We
      have hypothesized that quality control mechanisms for both transcripts and
      proteins work less efficiently during aging. In this manner +1 proteins may
      become manifest and contribute to age-related diseases.

PMID- 12200044
TI  - Introduction: a simple observation.

PMID- 12200045
TI  - Insights into antigen processing gained by direct analysis of the naturally
      processed class I MHC associated peptide repertoire.
AB  - MHC class I molecules are responsible for the presentation of antigenic peptides
      to CD8+ T lymphocytes. Based on their relatively promiscuous binding of peptides,
      these molecules display information derived from a large fraction of proteins
      that are made inside the cell. This review describes our characterization of the
      peptides comprising this repertoire, with particular attention given to their
      complexity and quantities, their post-translational modification, and the
      pathways leading to their expression.

PMID- 12200046
TI  - To DRiP or not to DRiP: generating peptide ligands for MHC class I molecules from
      biosynthesized proteins.

PMID- 12200047
TI  - The importance of the proteasome and subsequent proteolytic steps in the
      generation of antigenic peptides.
AB  - Three different proteolytic processes have been shown to be important in the
      generation of antigenic peptides displayed on MHC-class I molecules. The great
      majority of these peoptides are derived from oligopeptides produced during the
      degradation of intracellular proteins by the ubiquitin-proteasome pathway. Novel
      methods were developed to follow this process in vitro. When pure 26S proteasomes
      degrade the model substrate, ovalbumin, they produce the immunodominant peptide,
      SIINFEKL, occasionally, but more often an N-extended form of SIINFEKL. Interferon
      gamma stimulates antigen presentation in part by inducing new forms of the
      proteasome that are more efficient in antigen presentation, and in vitro these
      immunoproteasomes specifically produce more of the N-extended versions of
      SIINFEKL. In addition, gamma-interferon induces a novel 26S complex containing
      the 19S and 20S particles and the proteasome activator, PA28, which we show
      cleaves proteins in distinct ways. In vivo studies established that proteasomal
      cleavages produce the C-termini of antigenic peptides, but not their N-termini,
      which can be formed efficiently by aminopeptidases that trim longer proteasomal
      products to the presented epitopes. gamma-interferon stimulates this trimming
      process by inducing in the cytosol leucine aminopeptidase and a novel
      aminopeptidase in the ER. Peptides released by proteasomes, including antigenic
      peptides, are labile in cytosolic extracts, and most of the longer proteasome
      products are rapidly cleaved by the cytosolic enzyme, thymet oligopeptidase
      (TOP). If cells express large amounts of TOP, class I presentation decreases, and
      if TOP is inhibited, presentation increases. Thus, peptide degradation in the
      cytosol appears to limit the efficiency of antigen presentation.

PMID- 12200048
TI  - The role of the proteasome activator PA28 in MHC class I antigen processing.
AB  - The proteasome system is the major source for the generation of viral antigens
      and tumor antigens presented by major histocompatibility complex class I (MHC
      class I) molecules. A specific feature of the proteasomal antigen processing
      machinery is that five of its components are inducible by IFN-gamma. Two of these
      are the alpha and beta subunits of the proteasome activator PA28. Our results
      show that PA28 selectively up-regulates the presentation of viral MHC class I
      epitopes and that down regulation PA28 in tumor cells results in impaired
      presentation of a human TRP2 tumor antigen.

PMID- 12200049
TI  - MHC class I antigen processing regulated by cytosolic proteolysis-short cuts that
      alter peptide generation.
AB  - Cytotoxic T lymphocyte (CTL)-mediated immune responses rely on the efficiency of
      MHC class I ligand generation and presentation by antigen presenting cells
      (APCs). Whereas the abnormal expression of MHC molecules and transporters
      associated with antigen processing (TAPs) are commonly discussed as factors that
      modulate antigen presentation, much less is known about possible regulatory
      mechanisms at the level of proteolysis responsible for the generation of
      antigenic peptides. The ubiquitin-proteasome system is recognized as the major
      component responsible for this process in the cytosol and its activity can be
      regulated by cytokines, such as IFN-gamma. However, new evidence suggests the
      involvement of other proteases that can contribute to cytosolic proteolysis and
      therefore, to the quality and quantity of antigen production. Here, we review
      recent findings on an increasing number of proteolytic enzymes linked to antigen
      presentation, and we discuss how regulation of cytosolic protease activities
      might have implications for immune escape mechanisms that could be used by tumor
      cells and pathogens.

PMID- 12200050
TI  - Antigen degradation or presentation by MHC class I molecules via classical and
      non-classical pathways.
AB  - Major histocompatibility complex (MHC) class I molecules usually present
      endogenous peptides at the cell surface. This is the result of a cascade of
      events involving various dedicated proteins like the peptide transporter
      associated with antigen processing (TAP) and the ER chaperone tapasin. However,
      alternative ways for class I peptide loading exist which may be highly relevant
      in a process called cross-priming. Both pathways are described here in detail.
      One major difference between these pathways is that the proteases involved in the
      generation of peptides are different. How proteases and peptidases influence
      peptide generation and degradation will be discussed. These processes determine
      the amount of peptides available for TAP translocation and class I binding and
      ultimately the immune response.

PMID- 12200051
TI  - Beyond the proteasome: trimming, degradation and generation of MHC class I
      ligands by auxiliary proteases.
AB  - The proteasome is now recognized to be implicated in the generation of the vast
      majority of MHC class I ligands. Moreover, it is probably the only cytosolic
      protease generating their carboxyterminals. However, solid evidence documents a
      role of additional and only partly identified proteases in MHC class I antigen
      processing. Cytosolic tripeptidyl peptidase (TTP II) may be able to carry out
      some functions normally ascribed to the proteasome, including that of generating
      antigenic peptides. Several cytosolic enzymes, including bleomycin hydrolase (BH)
      and puromycin-sensitive aminopeptidase (PSA), but especially the IFNgamma
      inducible leucyl aminopeptidase (LAP), can trim the aminoterminal ends of class I
      ligands. The vast majority of cytosolic peptides is degraded, a process likely to
      limit antigen presentation, in which thimet oligopeptidase (TOP) may play an
      important role. Proteolytic activity in the secretory pathway, though much more
      limited than in the cytosol, also contributes to class I antigen presentation.
      Signal peptide fragments and peptides at the carboxyterminal end of various
      proteins targeted to the endoplasmic reticulum can be highly efficient TAP
      independent class I ligands. However, an as yet unidentified luminal trimming
      aminopeptidase may eventually turn out to play the most important role for class
      I ligand generation in the secretory pathway. Defining the extent of the
      involvement of cytosolic and luminal peptidases in class I antigen processing
      will be a challenging task for the future.

PMID- 12200052
TI  - Tapasin-the keystone of the loading complex optimizing peptide binding by MHC
      class I molecules in the endoplasmic reticulum.
AB  - MHC class I molecules are loaded with peptides that mostly originate from the
      degradation of cytosolic protein antigens and that are translocated across the
      endoplasmic reticulum (ER) membrane by the transporter associated with antigen
      processing (TAP). The ER-resident molecule tapasin (Tpn) is uniquely dedicated to
      tether class I molecules jointly with the chaperone calreticulin (Crt) and the
      oxidoreductase ERp57 to TAP. As learned from the study of a Tpn-deficient cell
      line and from mice harboring a disrupted Tpn gene, the transient association of
      class I molecules with Tpn and TAP is critically important for the stabilization
      of class I molecules and the optimization of the peptide cargo presented to
      cytotoxic T cells. The different functions of molecular domains of Tpn and the
      highly coordinated formation of the TAP-associated peptide loading complex will
      also be discussed in this review.

PMID- 12200053
TI  - Multiple proteases process viral antigens for presentation by MHC class I
      molecules to CD8(+) T lymphocytes.
AB  - Recognition by CD8(+) cytotoxic T lymphocytes of any intracellular viral protein
      requires its initial cytosolic proteolytic processing, the translocation of
      processed peptides to the endoplasmic reticulum via the transporters associated
      with antigen processing, and their binding to nascent major histocompatibility
      complex (MHC) class I molecules that then present the antigenic peptides at the
      infected cell surface. From initial assumptions that the multicatalytic and
      ubiquitous proteasome is the only protease capable of fully generating peptide
      ligands for MHC class I molecules, the last few years have seen the
      identification of a number of alternative proteases that contribute to endogenous
      antigen processing. Trimming by non-proteasomal proteases of precursor peptides
      produced by proteasomes is now a well-established fact. In addition, proteases
      that can process antigens in a fully proteasome-independent fashion have also
      been identified. The final level of presentation of many viral epitopes is
      probably the result of interplay between different proteolytic activities. This
      expands the number of tissues and physiological and pathological situations
      compatible with antigen presentation, as well as the universe of pathogen-derived
      sequences available for recognition by CD8(+) T lymphocytes.

PMID- 12200054
TI  - Alternative processing of endogenous or exogenous antigens extends the
      immunogenic, H-2 class I-restricted peptide repertoire.
AB  - We investigated the murine, MHC class I-restricted cytotoxic T lymphocyte (CTL)
      response to a viral antigen delivered by different vaccination strategies to
      either the endogenous, or an alternative exogenous processing pathway. The
      immunization techniques used primed distinct (though overlapping) repertoires of
      CTL epitopes. In vitro studies revealed evidence for the generation of
      immunogenic, L(d)- and K(b)-binding peptides from endocytosed, exogenous antigen
      by alternative (endolysosomal) processing. Endogenous antigens expressed by DNA
      vaccines as a stress protein-associated fusion proteins gains access from the
      cytosol to endolysosomal processing. Hence, exogenous as well as endogenous
      protein antigens can gain access to alternative processing pathways and can give
      rise to an extended repertoire of antigenic epitopes. These studies indicate
      novel ways for the rational design of vaccine candidates that can prime CTL
      responses.

PMID- 12200055
TI  - The guardians at the gate.

PMID- 12200056
TI  - Probing the roles of mast cells and basophils in natural and acquired immunity,
      physiology and disease.

PMID- 12200057
TI  - Cancer immunotherapy: novel strategies and clinical experiences.

PMID- 12200063
TI  - Adoptive transfer of T-cell immunity: gene transfer with MHC-restricted
      receptors.

PMID- 12200065
TI  - NK cells: a lesson from mismatched hematopoietic transplantation.
AB  - The past ten years have witnessed dramatic progress in our understanding of how
      natural killer (NK) cells function, their role in innate defenses and their
      possible exploitation in therapy. This article traces the major advances in these
      formerly mysterious cells, from the 'missing self' hypothesis and the first
      discovery of HLA-class I-specific inhibitory receptors to a recent major
      breakthrough that highlighted important perspectives and major expectations
      regarding the cure of life-threatening leukemias. The key role of 'alloreactive'
      NK cells in eradicating acute myeloid leukemias and in preventing both graft
      rejection and graft-versus-host disease, might lead to a true revolution in bone
      marrow transplantation. Thus, it might now be possible to search for appropriate
      HLA class I mismatches to set NK cells in action.

PMID- 12200066
TI  - Immature, semi-mature and fully mature dendritic cells: which signals induce
      tolerance or immunity?
AB  - Dendritic cells (DCs) are currently divided into tolerogenic immature and
      immunogenic mature differentiation stages. However, recent findings challenge
      this model by reporting mature DCs as inducers of regulatory CD4+ T cells in
      vivo. This implies that decisive tolerogenic and immunogenic maturation signals
      for DCs might exist. Closer inspection reveals that tolerance is observed when
      partial- or semi-maturation of DCs occurs, whereas only full DC maturation is
      immunogenic. The decisive immunogenic signal seems to be the release of
      proinflammatory cytokines from the DCs. Moreover, the semi-mature DC phenotype is
      comparable to steady-state migratory veiled DCs within the lymphatics, which seem
      to continuously tolerize lymph node T cells against tissue-derived self-antigens
      or apoptotic cells.

PMID- 12200067
TI  - Pathogen-specific regulatory T cells provoke a shift in the Th1/Th2 paradigm in
      immunity to infectious diseases.
AB  - Current dogma suggests that immunity to infection is controlled by distinct type
      1 (Th1) and type 2 (Th2) subpopulations of T cells discriminated on the basis of
      cytokine secretion and function. However, a further subtype of T cells, with
      immunosuppressive function and cytokine profiles distinct from either Th1 or Th2
      T cells, termed regulatory T (Tr) cells has been described. Although considered
      to have a role in the maintenance of self-tolerance, recent studies suggest that
      Tr cells can be induced against bacterial, viral and parasite antigens in vivo
      and might prevent infection-induced immunopathology or prolong pathogen
      persistence by suppressing protective Th1 responses. These observations have
      significant implications for our understanding of the role of T cells in immunity
      to infectious diseases and for the development of new therapies for immune
      mediated disorders.

PMID- 12200068
TI  - STI and beyond: the prospects of boosting anti-HIV immune responses.
AB  - Twenty years into the HIV epidemic, highly active antiretroviral therapy (HAART)
      represents the only effective intervention to control HIV-1 disease progression.
      However, the prospect of life-long treatment with HAART is challenging given
      cumulative drug toxicities, difficulties with adherence to complicated regimens
      and the looming emergence of drug-resistant viruses. The challenges are even
      greater in resource-poor settings where costs and logistical problems with
      delivery represent formidable obstacles. Alternative approaches to long-term
      control of viral replication and disease progression are clearly needed.

PMID- 12200069
TI  - Staphylococcal vaccines.
AB  - Vaccination has proved relatively unsuccessful against the common mammalian
      commensal bacteria Staphylococcus, despite almost a century of experimentation.
      Recent progress in clinical trials, animal models and molecular laboratories
      offers hope that these organisms might be partially or wholly controlled by
      augmenting host responses.

PMID- 12200073
TI  - High and low hemoglobin glycation phenotypes in type 1 diabetes: a challenge for
      interpretation of glycemic control.
AB  - This study tested the hypothesis that there are consistent individual differences
      in the relationship between glycated hemoglobin (HbA1c) and mean blood glucose
      (MBG) levels in individuals with similar preceding blood glucose levels. Blood
      glucose data were collected for up to 2.3 years by 128 children and adolescents
      with type 1 diabetes. HbA1c values were date-matched with MBG levels calculated
      from an average of 85 self-monitored blood glucose measurements collected in the
      previous 30 days. There was significant linear correlation between MBG and HbA1c
      (HbA1c=0.027xMBG+5.8, n=682, r=.71, P<.0001) but also wide variability in the
      population HbA1c response to MBG. We calculated a hemoglobin glycation index
      (HGI=observed HbA1c-predicted HbA1c) to quantify the magnitude and direction of
      the difference between each patient's set of observed and predicted HbA1c
      results. Likelihood ratio tests and t statistics showed that mean HGI were
      significantly different among individuals, and that 29% of the patients had HbA1c
      levels that were statistically significantly higher or lower than predicted by
      the regression equation. The observed individual differences in the relationship
      between MBG and HbA1c were not related to erythrocyte age and there was no
      evidence of analytical artifact. We interpret these results as possible evidence
      of high and low hemoglobin glycation phenotypes within the population. We
      conclude that MBG and HbA1c are not necessarily interchangeable estimates of
      glycemic control and that hemoglobin glycation phenotype may be important for the
      clinical assessment of diabetic patients.

PMID- 12200074
TI  - Mechanisms of inhibitory activity of the aldose reductase inhibitor, epalrestat,
      on high glucose-mediated endothelial injury: neutrophil-endothelial cell adhesion
      and surface expression of endothelial adhesion molecules.
AB  - BACKGROUND: We have previously reported that endothelial cells cultured in the
      presence of high concentrations of glucose (27.8 and 55.5 mM) exhibited enhanced
      neutrophil adhesion through increased expression of endothelial adhesion
      molecules via the activation of a protein kinase C (PKC)-dependent pathway. We
      also found that the aldose reductase inhibitor, epalrestat, inhibited these
      events, but the mechanisms for this inhibition remained unclear. In this study,
      we further investigated the inhibitory mechanisms of epalrestat with reference to
      PKC activation and nitric oxide (NO) production. METHODS: Human umbilical vein
      endothelial cells (HUVECs) were cultured for 48 h in glucose-rich medium and
      neutrophils from healthy volunteers were then added and allowed to adhere for 30
      min. Adhered neutrophils were quantified by measuring myeloperoxidase (MPO)
      activity and surface expression of endothelial adhesion molecules was determined
      by enzyme immunoassay. RESULTS: Culture in the presence of a high concentration
      of glucose (27.8 mM for 48 h) increased neutrophil-endothelial cell adhesion and
      surface expression of intercellular adhesion molecule-1 (ICAM-1), P-selectin, and
      E-selectin on endothelial cells. These phenomena were significantly inhibited by
      epalrestat (10 microM), while NO synthase (NOS) inhibitors reduced the inhibitory
      effects of this compound. In contrast, 10 nM phorbol 12-myristate 13-acetate
      (PMA), a PKC activator, showed similar effects as high glucose, and these effects
      were also inhibited by epalrestat. CONCLUSIONS: Our data suggested that
      epalrestat inhibited high glucose-mediated neutrophil-endothelial cell adhesion
      and expression of endothelial adhesion molecules not only through inhibition of a
      PKC-dependent pathway, but also through increased endothelial NO production.

PMID- 12200075
TI  - Determinants and estimation of healing times in diabetic foot ulcers.
AB  - AIMS: To assess the wound size reduction and time course for healing and to
      establish equations to predict the time course of wound healing in neuropathic,
      neuroischemic, and ischemic diabetic foot ulcers. METHODS: This prospective study
      evaluates wound healing over at least a 10-week period in 31 Type 1 or Type 2
      diabetic patients with plantar foot ulcers. Thirteen consecutive diabetic
      patients with neuropathic foot ulceration, 10 consecutive diabetic patients with
      neuroischemic ulceration, and 8 diabetic patients with peripheral occlusive
      vascular disease were selected for the study. All patients received identical
      ulcer wound care including use of proper footwear, non-weight-bearing limb
      support, use of appropriate antibiotics, debridement, tight control of serum
      glucose levels, and careful monitoring of the ulcer. Ulcer healing was assessed
      by planimetric measurement of the wound area every second week until wound
      healing. The time course of wound healing was calculated by the daily wound
      radius reduction. RESULTS: The wound area (mean+/-S.E.) in the patients with
      neuropathic foot ulceration was 61.2+/-17.1 at the beginning and 3.2+/-1.5 mm(2)
      after 70 days (P=.005). The wound radius decreased by 0.045 mm (95% confidence
      interval [CI] 0.039-0.055) per day, with most of the wound healing being achieved
      between the first and seventh week of ulcer care. The average healing time was
      77.7 (95% CI 62-93) days. In the neuroischemic group, the initial average wound
      area was 26.6+/-7.0 mm(2), and 6.25+/-1.7 mm(2) after 10 weeks (P=.007). The
      wound radius reduction was 0.019 mm/day (95% CI 0.017-0.023) with an average
      healing time of 123.4 (95% CI 101-145) days. The diabetic patients with
      peripheral occlusive vascular disease had an average wound size of 32.6+/-13.1 at
      the beginning and 23.9+/-10.7 mm(2) after 70 days of ulcer care (P=.06). The
      daily wound radius reduction was 0.0065 mm (95% CI 0.0039-0.0091). Average ulcer
      duration was 133 (95% CI 116-149) days, but three of eight patients achieved no
      wound healing. CONCLUSIONS: Providing standard care, the time course of wound
      healing in diabetic foot ulcers is predominantly determined by etiologic factors,
      and less by wound size. Taking wound etiology and wound radius into account, the
      expected healing time can reliably be estimated in neuropathic and neuroischemic
      ulcers.

PMID- 12200076
TI  - Leukocyte-endothelial cell adhesion molecule 1 (LECAM-1) polymorphism is
      associated with diabetic nephropathy in type 2 diabetes mellitus.
AB  - BACKGROUND/AIMS: Glomerular infiltration with monocytes/macrophages has been
      implicated in the pathogenesis of diabetic nephropathy. In this study, we
      evaluated the relationship between the genetic polymorphism in leukocyte
      endothelial adhesion molecule-1 (LECAM-1) and diabetic nephropathy in patients
      with type 2 diabetes mellitus. METHODS: We determined the frequency of the LECAM
      1 P213S genotype in 102 diabetic patients with diabetic nephropathy, 90 diabetic
      patients with no evidence of diabetic nephropathy, and 200 healthy control
      individuals. RESULTS: The frequency of the LECAM-1 213PP genotype and P allele in
      patients with diabetic nephropathy was significantly higher than that in patients
      without nephropathy (genotype 68% vs. 53%, chi(2)=6.78, P=.034; allele 83% vs.
      72%, chi(2)=6.26, P=.012). The LECAM-1 P213 genotype was associated with a 1.86
      fold increased risk for nephropathy independently of other risk factors.
      CONCLUSION: The data suggest that the LECAM-1 213PP genotype is a genetic risk
      factor for the development of nephropathy in type 2 diabetes mellitus.

PMID- 12200077
TI  - Absence of otoacoustic emissions in insulin-dependent diabetic patients: is there
      evidence for diabetic cochleopathy?
AB  - In order to evaluate cochlear function in Type 1 diabetes mellitus, this study
      analyses otoacoustic emissions (OAEs) on normal hearing subjects with diabetes
      and on controls. Patients with Type 1 diabetes (n=60), with a mean age of 31+/
      6.23 years, mean disease duration of 17.5+/-8.9 years, and mean HbA1c of 8.1+/
      1.8%, of whom 43% had signs of retinopathy and 28% had clinical signs of
      neuropathy, were studied. All patients underwent an OAE analysis and brainstem
      evoked potentials. Fifty-eight normal volunteers were used as controls for the
      OAE analysis. Seventeen patients (28.3%) had no OAEs in at least one ear and 10%
      in both ears. The mean intensity of the response was lower in diabetic subjects
      [7.1+/-4.4 vs. 10.9+/-9.3 dB SPL (sound pressure level)] than in controls. The
      cochlear impairment was over 5 dB for the 1-kHz frequency, which is the critical
      level for speech understanding. These findings suggest that cochleopathy can be
      detected in a relatively high proportion of subjects with Type 1 diabetes in
      spite of a normal audiometric hearing threshold.

PMID- 12200078
TI  - Usefulness of captopril renography to predict the benefits of renal artery
      revascularization or captopril treatment in hypertensive patients with diabetic
      nephropathy.
AB  - This retrospective study aimed to use captopril renography (CR) for predicting
      the benefits of captopril treatment in hypertensive patients with diabetic
      nephropathy. CR was utilized in 60 hypertensive patients with diabetic
      nephropathy for detecting the probability of renovascular hypertension (RVH) and
      predicting the benefits of renal artery revascularization or captopril treatment.
      Ten of the 60 patients showed a high probability of RVH with marked changes of
      the renogram curve after an oral intake of 50-mg captopril compared to baseline
      findings. All of the 10 patients confirmed significant main renal artery stenosis
      in all of them, bilaterally in four patients and unilaterally in the remaining
      six patients by renal angiographic findings. After successful revascularization,
      blood pressure was well controlled and renal function was preserved in all of the
      10 patients. The other 50 patients showed a low or intermediate probability of
      RVH with normal findings or unchanged on CR after 50-mg captopril. Then,
      captopril alone or combination treatment started and continued on 50 patients.
      After monitoring for at least 6 months, blood pressure was well controlled and
      renal function was preserved in all the 50 patients on captopril treatment. We
      conclude that CR should be considered as the standard diagnostic criteria of RVH
      and may be helpful in predicting the beneficial impact of captopril treatment in
      hypertensive patients with diabetic nephropathy.

PMID- 12200079
TI  - Evidence of impaired gallbladder function in patients with non-insulin-dependent
      diabetes mellitus by quantitative cholescintigraphy.
AB  - Non-insulin-dependent diabetes mellitus (NIDDM) is considered to predispose
      impaired gallbladder function and an increased prevalence of gallbladder disease.
      The aim of this study was to evaluate the gallbladder function of patients with
      NIDDM by quantitative technetium-99m-labeled imino-diacetic acid analogue (Tc-99m
      DISIDA) cholescintigraphy. One hundred and forty-five NIDDM patients (100 males,
      45 females; age: 58.7+/-9.5 years) with the absence of autonomic or peripheral
      neuropathy and without gallbladder or liver disorders were enrolled in this
      study. The patients were categorized by blood sugar control (HbA(1c)> or =10% as
      a poor blood sugar control group and HbA(1c)<10% as a good blood sugar control
      group) and disease duration (diabetic duration > or =10 years as a longer
      duration group and diabetic duration <10 years as a shorter-duration group). In
      addition, 60 normal controls (38 males, 22 females; age: 59.1+/-10.2 years) were
      also studied for comparison. All NIDDM patients and normal controls underwent Tc
      99m DISIDA cholescintigraphy, and the filling fraction (FF) and ejection fraction
      (EF) of gallbladder were calculated. The results showed significant difference
      between (1) NIDDM patients versus normal controls in FF and EF, (2) poor versus
      good blood sugar control of NIDDM patients in FF and EF, and (3) longer versus
      shorter disease duration of NIDDM patients in FF and EF. Our study, including a
      large number of subjects, showed that gallbladder function of patients with NIDDM
      is more impaired than the normal controls; and impaired gallbladder function in
      NIDDM patients is related to disease duration and blood sugar control.

PMID- 12200080
TI  - Elevated serum KL-6 concentrations in patients with diabetes mellitus.
AB  - To clarify the influence of blood glucose level or diabetes mellitus on serum KL
      6, a mucin-like glycoprotein, concentrations, they were measured against 176
      diabetic subjects, including receiving insulin (INS) group (n=54), oral
      antidiabetics (OAD) group (n=78), and diet and exercise (D&E) group (n=44). Serum
      KL-6 concentrations in the diabetic subjects were significantly greater than
      those in the normal healthy control subjects (643.0+/-32.7 U/ml, 206.5+/-6.1
      U/ml, P<.0001, respectively), and those in the INS and OAD groups were
      significantly greater than those in the D&E group (708.2+/-66.9, 691.7+/-51.9,
      and 476.6+/-34.9 U/ml, P<.05, P<.05, respectively). Serum KL-6 concentrations did
      not correlate with urine KL-6 concentrations (n=73, r= -.044, P= .74).
      Immunohistochemical staining of the diabetic kidneys with a monoclonal antibody
      to KL-6 antigen showed positive immunoreactivity on Henle's loop, renal tubules,
      and epithelial cells in Bowman's space of sclerosing glomerulus. In conclusion,
      diabetes mellitus or complications of diabetes mellitus resulted in serum KL-6
      elevation regardless of serum glucose level, but serum KL-6 concentrations were
      not influenced despite control of diabetes mellitus.

PMID- 12200081
TI  - Erythrocyte membrane glycation and NA(+)-K(+) levels in NIDDM.
AB  - Although there are many investigations on protein glycation in diabetic patients,
      many detailed studies are needed on this subject. In this study, the correlation
      between red cell membrane and serum protein glycation was investigated in NIDDM.
      The relation of membrane glycation to intracellular Na(+) and K(+) levels was
      also considered. Forty patients with NIDDM and 22 healthy subjects were included
      in the study. The membrane proteins were isolated, and total protein (TP(m)) and
      fructosamine (FA(m)) levels were determined. Serum glucose, fructosamine (FA(s))
      and total protein (TP(s)) levels were also measured. HbA(1C), red blood cell
      (RBC) and reticulocyte (RET) counts in whole blood were made in all samples.
      NA(+) and K(+) levels of both serum and RBC were determined. The patient group
      had lower levels of K(+)(RBC) (P<.001) and Na(+)(s) (P<.05) and RBC count
      (P<.05), and higher levels of FA(m) (P<.001), Na(+)(RBC) (P<.01), K(+)(s)
      (P<.01), glucose (P<.001) and HbA(1C) (P<.001) than those of controls. The ratios
      of FA(s)/TP(s) (P<.001) and FA(m)/TP(m) (P<.001) were higher in patients than in
      control. As a result, HbA(1C) levels and the ratio of FA(m)/TP(m) were high in
      NIDDM patients (P<.001) and these patients have slight negative correlations in
      FA(m)/TP(m) and FA(s)/TP(s) (P<.05). On the other hand, that there is no
      correlation between RBC membrane protein glycation and RBC Na(+) and K(+) levels
      may be caused by the fact that the membrane protein glycation is lower than that
      of other soluble proteins and that the membrane proteins are functional with
      respect to Na(+)-K(+) transport.

PMID- 12200082
TI  - Selective pericyte degeneration in the retinal capillaries of galactose-fed dogs
      results from apoptosis linked to aldose reductase-catalyzed galactitol
      accumulation.
AB  - Galactose-fed dogs develop retinal capillary changes similar to diabetic
      retinopathy with pericyte degeneration as the initial lesion. This is followed by
      the formation of microaneurysms, hemorrhages, and some areas of acellularity. To
      investigate the mechanisms for selective pericyte degeneration, retinal capillary
      pericytes and endothelial cells isolated from beagle dog retina were cultured for
      2 weeks in Dulbecco's modified Eagle's medium (DMEM) containing 50 mM D
      galactose. Apoptosis was detected in pericytes but not endothelial cells by in
      situ terminal deoxynucleotidyl transferase (TdT)-mediated biotin-dUTP nick end
      labelling (TUNEL) staining and the DNA fragmentation assay on agarose gel
      electrophoresis. This apoptosis was prevented by the addition of the aldose
      reductase inhibitor AL 1576 to the culture medium containing galactose. Apoptosis
      was not observed when pericytes were similarly cultured in control DMEM medium.
      These data support the premise that the selective degeneration of retinal
      capillary pericytes observed in galactose-fed dogs is linked to increased aldose
      reductase activity in these cells.

PMID- 12200083
TI  - Heat-shock protein (HSP70) response in the eastern oyster, Crassostrea virginica,
      exposed to PAHs sorbed to suspended artificial clay particles and to suspended
      field contaminated sediments.
AB  - Sediments are a potentially significant source of pollutants, containing not only
      organic contaminants but heavy metals as well. The heat shock protein response
      (HSP70 family) in the eastern oyster exposed to suspended clay particles spiked
      with polynuclear aromatic hydrocarbons (PAHs) and to suspended field contaminated
      sediments (SFCS) was investigated. In experiment 1, oysters were exposed to 1.0,
      1.5 or 2.0 g suspended clay particles with concentrations of 65.6, 159.0 and 242
      micro g PAHs per g of wet clay particles, respectively, and sampled after 40
      days. Controls were exposed to 0, 1.0, 1.5, and 2.0 g suspended unspiked clay
      particles. In experiment 2, oysters were exposed to 0, 1.0, 1.5, and 2.0 g SFCS
      and the HSP70 expression was determined after 5, 10, 20 and 40 days exposure.
      Oysters exposed to suspended clay particles spiked with PAHs showed a significant
      increase in HSP70 levels, while oysters exposed to 1.0, 1.5 or 2.0 g suspended
      unspiked clay particles did not show changes (P=0.78) in HSP70 levels compared to
      the group receiving 0 g clay particles. Exposure to the SFCS resulted in a
      significant increase in HSP70 as a function of exposure (P<0.001) and treatment
      (P=0.006). The response, however, was not dose dependent. Compared to the control
      group (0 g SFCS), groups exposed to 1.0, 1.5 and 2.0 g SFCS reached significantly
      higher levels in HSP70 at 40 days of exposure, with those exposed to 2.0 g SFCS
      expressing the highest levels. The HSP70 expression for each treatment showed
      fluctuations at various time intervals. No mortalities were recorded during the
      exposure experiments. The major contaminants in the SFCS were PAHs, heavy metals
      and polychlorinated biphenyls (PCBs). These results reveal that exposure to PAHs
      sorbed to clay particles and to SFCS induced a HSP70 response in the eastern
      oyster.

PMID- 12200084
TI  - Possible disruption of pheromonal communication by humic acid in the goldfish,
      Carassius auratus.
AB  - Humic acids are large, complex, organic molecules which are ubiquitous components
      of aquatic environments as products of degradation of plant material. In aqueous
      solution they form microvesicles. As many teleost pheromones are steroidal in
      nature, we hypothesised that they would preferentially dissolve in the organic,
      hydrophobic core of these vesicles instead of in water and therefore be
      unavailable for detection. This would have obvious and profound effects on many
      aspects of fish biology. To test this hypothesis we recorded electro-olfactogram
      (EOG) response of the goldfish (Carassius auratus) olfactory epithelium to the
      pheromones 17 alpha,20 beta-dihydroxy-4-pregnen-3-one (1720 beta-P), its
      sulphated conjugate (1720 beta-P-SO(4)) and prostaglandin F(2alpha)
      (PGF(2alpha)), all at 10(-11) to 10(-8) M, in the absence and presence of humic
      acids (1-1000 m x gl(-1)). At nearly all concentrations of humic acid tested,
      there was a significant attenuation of the amplitude of the initial (phasic)
      response to 1720 beta-P compared to 1720 beta-P alone. At higher concentrations
      of humic acid, the EOG response to 1720 beta-P was often completely obliterated,
      suggesting that the concentration of the pheromone available to the olfactory
      epithelium was below the threshold of detection. Exposure of the olfactory
      epithelium to humic acid did not cause any short-term loss of sensitivity to 1720
      beta-P per se. Furthermore, simultaneous recording of electro-encephalograms from
      the olfactory bulb demonstrated that the nervous activity evoked by the same
      concentration of 1720 beta-P was less intense in the presence of humic acid than
      its absence. PGF(2alpha) is non-steroidal and much more soluble in water. In
      contrast to 1720 beta-P, only the higher concentrations of humic acid (100 and
      1000 mg x l(-1)) significantly diminished the EOG amplitude. 1720 beta-P-SO(4) is
      detected via a distinct olfactory mechanism to the free form. Given that the
      sulphate group increases the water solubility, we predicted that the effect of
      humic acid would be reduced. However, the effect of humic acid on EOG amplitude
      in response to 1720 beta-P-SO(4) was similar to that of the free form. We suggest
      that the steroid portion of the molecule adsorbs onto the surface of the humic
      acid microvesicles and is still effectively unavailable for olfactory detection.
      In conclusion, humic acid may significantly reduce the concentration of 1720 beta
      P and 1720 beta-P-SO(4) available for detection by Carassius auratus in natural
      environments. Furthermore, as many teleost pheromones are steroid derivatives,
      this phenomenon may be applicable to chemical communication systems in teleosts
      in general.

PMID- 12200085
TI  - Effects of husbandry practices, gender, and normal physiological variation on
      growth and reproduction of Japanese medaka, Oryzias latipes.
AB  - Japanese medaka, Oryzias latipes, are currently used in a variety of research
      applications for toxicological and carcinogenesis research, yet the impact of
      certain husbandry factors on study outcome has received limited attention. In
      this study, we demonstrated significant effects of stocking density (SD), dietary
      restriction (DR) and photoperiod on somatic growth in medaka. Higher stocking
      densities significantly inhibited somatic and hepatic growth in females, while
      having no similar effects on males. Daily egg production declined in a step-wise
      manner in groups of fish stocked at densities ranging from 0.38 to 2.6 fish per
      l. Significantly slower somatic growth was observed in fish fed on a mildly
      restrictive dietary protocol compared with those fish fed to excess. Further
      significant declines were observed in somatic growth of fish fed at a rate
      comparable to that used in research studies (3-4% body weight (BW) per day). Fish
      reared at an 8-h light:16-h dark (8L/16D) photoperiod were significantly smaller
      than cohorts reared at a 16-h light:8-h dark (16L/8D) photoperiod and female
      sexual maturity was delayed in the short photoperiod cohort. In normal female
      medaka, a high degree of individual variation was observed in daily egg
      production, as well as diurnal fluctuations in ovarian weight, gonadosomatic
      index (GSI) and hepatosomatic index (HSI). These results indicate some husbandry
      factors affect growth, sexual maturation and egg production in medaka and should
      be taken into consideration in studies evaluating endpoints that may be impacted
      by growth and reproductive performance, i.e. carcinogenesis and endocrine
      disruption studies. The high degree of individual variation among normal females
      and daily fluctuations in organ weights should also be considered in study
      design.

PMID- 12200086
TI  - Effects of long-term nonylphenol exposure on gonadal development and biomarkers
      of estrogenicity in juvenile rainbow trout Oncorhynchus mykiss.
AB  - Environmental pollutants with estrogenic activity including nonylphenol (NP) have
      the potential to alter gonadal development and reproduction of wild fish. To
      investigate the estrogenic action of environmentally relevant concentrations of
      NP, rainbow trout (Oncorhynchus mykiss) were continuously exposed during the
      embryonic, larval and juvenile life stage to 1.05 and 10.17 microg/l NP for 1
      year, and sexual differentiation, vitellogenin (VG), VG mRNA, and zona radiata
      protein (ZRP) expression were examined after that period. The applied NP
      concentrations did not affect mortality and hatching rates, and did not have an
      influence on the body weight of 1-year-old fish. No occurrence of testis-ova was
      observed and sex-ratios of NP exposed groups of fish were unchanged when compared
      with control groups. The induction of VG and ZRP expression was a more sensitive
      reaction to the presence of NP than the formation of testis-ova and the reversal
      of sex. Increased VG expression in trout liver occurred already at 1.05 microg/l
      NP, whereas VG mRNA levels, quantified by competitive RT-PCR, were not
      significantly elevated in NP exposed fish. ZRP contents were significantly higher
      at 10.17 microg/l NP. Since induction of VG did not occur in all fish exposed to
      1 or 10 microg/l NP and ZRP induction did not occur in all fish exposed to 10
      microg/l, some individuals may be more affected by exposure to NP than others.
      This study demonstrates that NP concentrations typically found in sewage
      treatment effluents and some rivers do not affect sexual differentiation in
      rainbow trout, but induce VG and ZRP expression in the liver of exposed fish.

PMID- 12200087
TI  - Effects of enteric bacterial and cyanobacterial lipopolysaccharides, and of
      microcystin-LR, on glutathione S-transferase activities in zebra fish (Danio
      rerio).
AB  - Cyanobacteria (blue-green algae) can produce a variety of toxins including
      hepatotoxins e.g. microcystins, and endotoxins such as lipopolysaccharides (LPS).
      The combined effects of such toxins on fish are little known. This study examines
      the activities of microsomal (m) and soluble (s) glutathione S-transferases (GST)
      from embryos of the zebra fish, Danio rerio at the prim six embryo stage, which
      had been exposed since fertilisation to LPS from different sources. A further aim
      was to see how activity was affected by co-exposure to LPS and microcystin-LR (MC
      LR). LPS were obtained from Salmonella typhimurium, Escherichia coli, a
      laboratory culture of Microcystis CYA 43 and natural cyanobacterial blooms of
      Microcystis and Gloeotrichia. Following in vivo exposure of embryos to each of
      the LPS preparations, mGST activity was significantly reduced (from 0.50 to
      between 0.06 and 0.32 nanokatals per milligram (nkat mg(-1)) protein). sGST
      activity in vivo was significantly reduced (from 1.05 to between 0.19 and 0.22
      nkat mg(-1) protein) after exposure of embryos to each of the cyanobacterial LPS
      preparations, but not in response to S. typhimurium or E. coli LPS. Activities of
      both m- and sGSTs were reduced after co-exposure to MC-LR and cyanobacterial LPS,
      but only mGST activity was reduced in the S. typhimurium and E. coli LPS-treated
      embryos. In vitro preparations of GST from adult and prim six embryo D. rerio
      showed no significant changes in enzyme activity in response to the LPS
      preparations with the exception of Gloeotrichia bloom LPS, where mGST was reduced
      in adult and embryo preparations. The present study represents the first
      investigations into the effects of cyanobacterial LPS on the phase-II microcystin
      detoxication mechanism. LPS preparations, whether from axenic cyanobacteria or
      cyanobacterial blooms, are potentially capable of significantly reducing activity
      of both the s- and mGSTs, so reducing the capacity of D. rerio to detoxicate
      microcystins. The results presented here have wide ranging implications for both
      animal and human health.

PMID- 12200088
TI  - Seasonal variation of plasmatic and hepatic vitellogenin and EROD activity in
      carp, Cyprinus carpio, in relation to sewage treatment plants.
AB  - Concern about the health of aquatic fauna living in waters containing
      biologically active levels of estrogenic compounds is particularly focused on the
      effects on their reproductive success. To that end, carp, Cyprinus carpio, a
      feral fish living in warm waters of Southern Europe (NE Spain), were selected for
      signs of estrogenicity. The study area covered two tributaries (the Anoia and the
      Cardener) of the Llobregat River both known to be polluted by estrogenic
      compounds. The estrogenicity in the carp was measured as vitellogenin (VTG)
      presence in males and alterations in VTG levels in females, over a 6-month
      period, embracing both the pre- and post-spawning seasons. VTG content was
      measured in both the plasma and liver, the latter being the organ that
      synthesizes it. Also, hepatic 7-ethoxyresorufin O-deethylase (EROD) activity was
      recorded, as interactions of xenoestrogens and oestradiol have been reported to
      affect this enzymatic activity. The estrogenicity of these rivers was more
      evident in the Anoia at the location downstream from the sewage treatment plant
      (STP), by elevated levels of VTG in males and by the presence of some intersex
      individuals. In the Cardener, no intersex fish were found and male plasmatic VTG
      was not so highly elevated. However presence of hepatic VTG, in up to 54% of the
      male fish analyzed, proved exposure to xenoestrogens. In females, VTG fluctuated
      according to the biological cycle with a plasmatic peak in May and an earlier
      maximal in the liver. However, this pattern was altered in the locations with
      higher xenoestrogens presence. EROD activity showed differences between sexes,
      with higher activity in males than females, as well as site-related differences
      (up to one order of magnitude) in the same river. These differences were even
      greater than those detected between rivers. A seasonal trend was also seen in
      EROD activity with higher induction towards the summer in both males and females.

PMID- 12200089
TI  - Development of a multispecies system for testing reproductive effects on aquatic
      invertebrates. Experience with Daphnia magna, Chironomus prasinus and Lymnaea
      peregra.
AB  - A cost /effective innovative approach combining three freshwater invertebrates:
      the cladoceran Daphnia magna, the insect Chironomus prasinus and the
      basommatophoran snail Lymnaea peregra, in a single system is presented. The
      selection combines different reproductive strategies: parthenogenesis, sexual
      reproduction and hermaphroditism, respectively, and covers water column,
      sediment, food and contact exposure. Results confirm the system's capacity. In 46
      days, multi-generation, whole-life-cycle, and chronic reproduction assays can be
      achieved for D. magna, C. prasinus and L. peregra, respectively. The 21-day D.
      magna test is commonly used to assess the effects of chemicals on aquatic
      invertebrates. Wide concerns on its suitability for testing endocrine disrupting
      chemicals have been raised, particularly for substances with estrogenic
      activities. The combination of three species with different reproductive
      strategies offer a suitable approach for assessing ecologically relevant effects
      related to any mechanism of action, including endocrine disruption.

PMID- 12200090
TI  - Seasonal variation in carbohydrate and lipid metabolism of yellow perch (Perca
      flavescens) chronically exposed to metals in the field.
AB  - The effects of heavy metals on growth, intermediary metabolism and enzyme
      activities were investigated in yellow perch (Perca flavescens), sampled in
      summer and fall from lakes situated along a contamination gradient of Cd, Zn and
      Cu in the mining region of Rouyn-Noranda, Quebec. An exposure-dependent decrease
      in condition factor was observed in both seasons. Liver glycogen and triglyceride
      reserves were higher in summer than in fall in fish from the reference lake,
      while the seasonal pattern was different in fish from the contaminated lakes.
      Plasma free fatty acids (FFA) levels were also influenced by season and
      contamination. Activities of malic enzyme (ME) and glucose 6-phosphate
      dehydrogenase (G6PDH) in the liver were higher in the summer than in the fall in
      reference lakes whereas no seasonal variations were detected in fish from
      contaminated lakes. Activities of pyruvate kinase (PyK), aspartate transaminase
      (AST), phosphoenolpyruvate carboxykinase (PEPCK) and malate dehydrogenase (MDH),
      were higher in fish from contaminated lakes in fall but not in summer. Chronic
      exposure of yellow perch to sublethal levels of heavy metals impairs growth and
      alters the seasonal cycling of liver glycogen and triglycerides as well as the
      activities of metabolic enzymes.

PMID- 12200091
TI  - Expression, cellular distribution and induction of cytochrome p4501A (CYP1A) in
      gilthead seabream, Sparus aurata, brain.
AB  - The presence and induction of cytochrome p4501A (CYP1A) in the brain of a teleost
      fish, the seabream, Sparus aurata, was studied. Cerebral CYP1A expression of
      control fish or fish exposed to various concentrations of 2,3,7,8
      tetrachlorodibenzo-p-dioxin (TCDD) was assessed at the enzyme activity level
      measured as 7-ethoxyresorufin-O-deethylase; at the protein level-measured by
      means of Western blot and ELISA; and at the mRNA level-estimated by means of RT
      PCR. Cellular localization of CYP1A in the brain tissue was studied using
      immunohistochemistry. In non-exposed control fish, expression of CYP1A could be
      demonstrated only in the olfactory bulbs. After TCDD exposure, the olfactory
      bulbs still showed the highest expression levels of CYP1A, however, other brain
      regions were now CYP1A-positive as well. Immunohistochemical examination of brain
      tissue sections from control fish demonstrated CYP1A immunoreactive fibers in the
      ventral telencephalon, in the glomerular layer of the olfactory bulbs, and in the
      endothelia of the cerebral vascular system. The same structures reacted positive
      in TCDD-exposed fish, but cell bodies and fibers from additional brain areas
      including telencephalon, diencephalon, mesencephalon and cerebellum showed CYP1A
      immunostaining. In the pituitary of TCDD-treated fish, putative GTH cells were
      positive for CYP1A, whereas in control fish no staining of the adenohypophysis
      was observed. The present findings provide evidence for basal expression of CYP1A
      in the telencephalon of Sparus aurata, and for the presence of inducible CYP1A in
      all other major brain regions, including the pituitary.

PMID- 12200092
TI  - Exposure to exogenous 17beta-oestradiol disrupts p450aromB mRNA expression in the
      brain and gonad of adult fathead minnows (Pimephales promelas).
AB  - Oestrogens are key regulators in sexual differentiation and development in higher
      vertebrates. P450 aromatase (p450arom) is the steroidogenic enzyme responsible
      for the synthesis of oestrogens from aromatisable androgens. Effects of endocrine
      disrupting chemicals on steroidogenic enzyme gene expression have received little
      attention so far, yet it is potentially a major pathway for sexual disruption. In
      this 14-day study the effects of exogenous 17beta-oestradiol (E2) at
      environmentally relevant concentrations were assessed on gene expression of
      p450aromB in the gonad and brain of maturing male and female fathead minnows
      (FHM). Exposure to E2 resulted in an oestrogenic response as shown by a dose
      dependent induction of plasma vitellogenin (VTG) in female and male fish and a
      dose-dependent inhibition of testis growth. There was an effect of exposure to E2
      on p450aromB mRNA expression in the gonads; E2 up-regulated p450aromB mRNA
      expression in the testis and ovary in a dose-response manner after 14 days of
      exposure. In male brain, p450aromB mRNA concentrations were significantly reduced
      in fish exposed to 100 and 320 ng E2/l on day 4, but on day 14 were elevated in
      males exposed to both 32 and 100 ng E2/l. No effects of E2 on p450aromB mRNA
      expression occurred in the brain of females. The results of this study show that
      concentrations of E2 found in the environment can have disruptive effects on key
      steroidogenic enzyme pathways that control sexual development in fish.

PMID- 12200093
TI  - Trends in smoking, diet, physical exercise, and attitudes toward health in
      European university students from 13 countries, 1990-2000.
AB  - BACKGROUND: Smoking, diet, and physical exercise are key determinants of health.
      This study assessed changes over 10 years and their relationship to changes in
      health beliefs and risk awareness. METHOD: A survey was carried out of university
      students from 13 European countries (Belgium, England, France, Germany, Greece,
      Hungary, Iceland, Ireland, Italy, The Netherlands, Poland, Portugal, and Spain)
      in 1990 (4,701 men, 5,729 women) and repeated in 2000 (4,604 men, 5,732 women).
      We assessed smoking, exercise, fruit and fat intake, beliefs in the importance of
      behaviors for health, and awareness of the influence of behaviors on heart
      disease risk. RESULTS: Smoking prevalence increased and fruit consumption
      decreased between 1990 and 2000, while physical exercise and fat intake were more
      stable. There were large variations between country samples. Health beliefs
      weakened, with marked decreases in beliefs about smoking and diet. Across country
      samples, changes in beliefs correlated with changes in the prevalence of
      behaviors. Awareness of the effects of smoking and exercise was stable, but
      knowledge of the role of fat intake increased over the decade. CONCLUSIONS: The
      differences in health behaviors, beliefs, and risk awareness between the two
      surveys were disappointing in this educated sector of young adult Europeans. The
      association between changes in beliefs and prevalence of behavior emphasizes the
      importance of enhancing positive attitudes to healthier lifestyles.

PMID- 12200094
TI  - Trends in food locations and sources among adolescents and young adults.
AB  - BACKGROUND: The aim of this study was to determine overall trends of total energy
      intake by food location and food type in diets of adolescents and young adults.
      METHODS: This study used a nationally representative sample of 16,810
      individuals, ages 12-29 from the 1977 to 1978 Nationwide Food Consumption Survey
      and the 1989-1991 and 1994-1996 Continuing Surveys of Food Intake by Individuals.
      For each survey year, the percentage of total energy intake from meals and snacks
      was calculated for adolescents ages 12-18 and young adults ages 19-29. The
      percentage of energy intake by location and for specific food group was computed
      for both age groups, separately. RESULTS: Both adolescents and young adults are
      obtaining less of their energy intake at home and more at restaurants and fast
      food places. This is predominantly seen among calories from snacking occasions
      for adolescents and both meals and snacks among the older age group. Significant
      increases in consumption of pizza, cheeseburgers, and salty snacks and decreases
      in consumption of desserts and certain milk and meat products by both age groups
      are shown. CONCLUSIONS: To improve the diets of adolescents and young adults,
      healthy food choices outside the home need to be as readily available as the
      foods which have increased in popularity over the past 20 years.

PMID- 12200095
TI  - Smoking and other risk factors for bladder cancer in women.
AB  - BACKGROUND: Bladder cancer is three to five times more frequent in men than in
      women, and hence only a few studies have focused only on females. METHODS: A case
      control study was conducted between 1985 and 1992 in two areas of northern Italy,
      and included 110 women with histologically confirmed bladder cancer and 298
      controls, admitted to the same network of hospitals of cases for acute, non
      neoplastic, non-urinary or genital tract diseases. Multivariate odds ratios (ORs)
      were computed using unconditional multiple logistic regression. RESULTS: Compared
      to never smokers, current smokers (OR = 2.87) had significantly elevated risks of
      bladder cancer. High intake of vegetables was inversely related to the disease
      (OR = 0.32), while history of occupation in chemical, dyes/paints or
      pharmaceutical industry (OR = 3.01) was directly associated to risk of bladder
      cancer. The OR was 3.29 for ever use of menopause hormone replacement therapy.
      CONCLUSIONS: This study confirms that cigarette smoking is the prominent risk
      factor for bladder cancer in women as in men, with similar relations in both
      sexes. It also confirms that selected occupational factors are related to bladder
      cancer risk, and supports a favourable role of vegetables. The apparent relation
      with hormone replacement therapy in menopause needs interpretation and further
      investigation.

PMID- 12200096
TI  - Prospective study of educational background and stomach cancer in Japan.
AB  - BACKGROUND: Different lifestyle choices are commonly regarded as a reflection of
      socioeconomic status, and the latter is inversely correlated with the risk of
      developing stomach cancer. However, the details of this association are still
      unclear in terms of the degree to which lifestyle factors are having impact. To
      explain the correlation between socioeconomic status and stomach cancer, we
      therefore examined the roles played by different lifestyle factors. METHODS: A
      prospective cohort study of diet and cancer was initiated in Japan during 1988.
      Data were collected by means of a self-administered questionnaire. A follow-up
      survey was conducted annually, and the cause of death was recorded from the death
      certificate. The total of 127,477 study participants resided in 45 areas of
      Japan, and we retrieved data for 18,746 men and 26,184 women for the present
      analysis. After 328,030 person-years of follow-up, 379 deaths from stomach cancer
      were detected: 261 in men and 118 in women. RESULTS: For men, the age-adjusted
      relative risk was lowest in the highly educated group (relative risk = 0.72, 95%
      CI: 0.50-1.04). Relative risk after adjustment for age and dietary choices
      (including pickles, vegetables, fruit, green tea, and preference for salty foods)
      was the same as the age-adjusted relative risk (relative risk = 0.72, 95% CI:
      0.50-1.04). CONCLUSION: The expected inverse correlation between education level
      and death from stomach cancer was observed in men. However, this association
      could not be explained by differences in dietary habits, smoking, or alcohol
      consumption associated with socioeconomic status.

PMID- 12200097
TI  - Exploring hepatitis B vaccination acceptance among young men who have sex with
      men: facilitators and barriers.
AB  - BACKGROUND: Studies continue to show that the majority of men who have sex with
      men in the United States remain unvaccinated against hepatitis B despite the
      licensure of an efficacious vaccine in 1982. METHODS: A theory-based, qualitative
      approach is used to explore acceptance of hepatitis B vaccination among men who
      have sex with men residing in Birmingham, Alabama. RESULTS: A total of 62 self
      identified men who have sex with men (mean age = 25 +/- 2.3; range: 18-36 years)
      participated in one of eight focus groups. Among the findings of this study,
      participants reported low levels of perceived susceptibility to infection; lacked
      basic information about hepatitis B and hepatitis B vaccination; did not perceive
      their providers to be comfortable with discussing their same-sex sexual behavior;
      did not identify tangible or intangible benefits to vaccination; had limited
      access to health care and had little continuity of care; did not trust federally
      supported vaccination efforts; and reported the inundation of HIV prevention
      messages hampered their receptivity to health messages in general. CONCLUSIONS:
      There is an urgent need to enhance awareness and facilitate hepatitis B
      vaccination among men who have sex with men. While further research is necessary,
      our findings indicate that numerous barriers to hepatitis B vaccination exist
      that may result in low vaccination rates. Prevention efforts would benefit from
      addressing these barriers.

PMID- 12200098
TI  - Understanding physician agreement with varicella immunization guidelines.
AB  - BACKGROUND: Although varicella vaccine was licensed in 1995, immunization rates
      are only moderate. This study identifies factors associated with physician self
      reported likelihood of recommending varicella vaccination to patients. METHODS:
      Two hundred eighty-one Minnesota and Pennsylvania primary care physicians who
      participated in surveys on barriers to vaccination in 1990-1991 and 1993 were
      surveyed in 1999, assessing physicians' beliefs about varicella disease and
      vaccine and their self-reported likelihood of recommending varicella vaccine to
      three age groups of children. RESULTS: Most (79, 80, and 83%) were likely to
      recommend varicella vaccine for 12- to 18-month old, 4- to 6-year-old, and 11- to
      12-year old children, respectively, and most (78%) agreed with national
      recommendations to vaccinate. If physicians believed that the vaccine would fail,
      they were less likely to recommend varicella vaccination for 12- to 18-month-old
      (70% vs 85%, P = 0.001) and 4- to 6-year-old (83% vs 85%, P = 0.001) children,
      than if they believed in its efficacy. Pediatricians were more likely to
      recommend varicella vaccine than were family physicians and general practitioners
      (P < 0.01). CONCLUSIONS: Physicians, especially pediatricians, report that they
      recommend varicella vaccination when they agree with national recommendations,
      believe in the efficacy of the vaccine, and perceive that parents want the
      vaccine for their children.

PMID- 12200099
TI  - Pregnancy planning and folic acid supplement use: results from a survey in
      Quebec.
AB  - BACKGROUND: To decrease the risk of neural tube defects, all women planning
      pregnancy or capable of becoming pregnant should take folic acid supplements. The
      aim of the study was to describe the association between pregnancy planning and
      vitamin supplement use. METHODS: A total of 1,858 pregnant women registered for a
      prenatal ultrasound examination in the Monteregie region, Province of Quebec,
      Canada, completed a questionnaire between November 1997 and May 1998. Pregnancy
      planning was described by six ordinal variables, which were included in a
      nonlinear principal component analysis. The main dimension representing the
      intensity of pregnancy planning was used as the dependent variable in a
      multivariate linear regression model, and as a basis for assessing vitamin use
      according to four levels of planning. RESULTS: A majority of women scored high
      for intensity of pregnancy planning. Planning intensity score increased with age
      and was higher among women who attended university, had a family income greater
      than CAD $30,000, and were married. Vitamin use in the period prior to conception
      occurred with a frequency of 27.5%, increasing moderately with planning intensity
      scores. Overall, only 13.5% of fetuses were exposed to adequate doses of folic
      acid. CONCLUSION: A promotion campaign selectively targeting women likely to plan
      a pregnancy could have a significant impact in reducing neural tube defect
      incidence.

PMID- 12200100
TI  - Evaluation of an enhanced approach to the dissemination of the North American
      Guidelines for Children's Agricultural Tasks: a randomized controlled trial.
AB  - BACKGROUND: The North American Guidelines for Children's Agricultural Tasks were
      developed to assist farm parents in assigning developmentally appropriate and
      safe work to children aged 7 to 16 years. The purpose of this study was to
      compare the efficacy of the standard dissemination strategy with an enhanced,
      multiphased, dissemination approach in influencing parents to use/apply North
      American Guidelines for Children's Agricultural Tasks when assigning farm work to
      their children. METHODS: A multisite-randomized trial was performed. During 1999,
      498 farms in Canada and the United States were enrolled. Enhanced dissemination
      activities included the provision of a video, personalized child development
      information, and supportive telephone calls. Follow-up with all farms occurred
      during the fall of 2000 to assess parental reaction to North American Guidelines
      for Children's Agricultural Tasks and to determine whether North American
      Guidelines for Children's Agricultural Tasks were actually used. RESULTS:
      Proportions of parents who were actively using North American Guidelines for
      Children's Agricultural Tasks at 15 months were 108/218 (49.5%) and 83/224
      (37.1%) in the experimental and control groups, respectively (difference: 12.5%,
      95% CI: 3.4, 21.7). Parental knowledge of the content of North American
      Guidelines for Children's Agricultural Tasks was also increased in the enhanced
      dissemination group. CONCLUSION: These results have important implications for
      dissemination of the North American Guidelines for Children's Agricultural Tasks
      resources. An enhanced dissemination strategy appears to increase the likelihood
      that North American Guidelines for Children's Agricultural Tasks will be used by
      farm parents.

PMID- 12200101
TI  - Prevention of Lyme disease in Dutch children: analysis of determinants of tick
      inspection by parents.
AB  - BACKGROUND: This study examined factors that discriminate between parents who
      regularly inspect their children for ticks and those who do not do so. METHODS:
      Knowledge, cognitive and emotional attitudes, social influences, and self
      efficacy expectations were assessed in 230 parents living in high endemic
      regions. RESULTS: Regression analysis showed that moral norms, emotional
      attitude, anticipated regret, role models, and stress self-efficacy were
      positively associated with inspection behavior. CONCLUSIONS: Health education
      programs not only need to stimulate parental knowledge and discuss the health
      effects of tick bite prevention, they also need to stress the emotional benefits
      of tick bite prevention for children and parents and induce positive norms toward
      inspecting others. Furthermore, they need to stimulate openness about inspection
      behaviors, since the modeling examples of partners, relatives, and grandparents
      and the behavior of friends discriminate between inspecting and noninspecting
      parents. Finally, education programs should clearly indicate how tick inspection
      works, how the need for it should be communicated to the children, and how to
      take enough time to do it.

PMID- 12200102
TI  - The escalating cost and prevalence of alternative medicine.
AB  - BACKGROUND: The purpose of this study was to measure trends in the prevalence and
      cost of alternative medicines and alternative practitioner use in an Australian
      population and to obtain a profile of users and their beliefs. METHODS: In 2000,
      we repeated a 1993 representative population survey of persons ages 15 years or
      older living in South Australia, which provided 3,027 personal interviews. We
      assessed the rates of use, types of alternative medicine and therapists, costs,
      and beliefs of users and nonusers. Comparisons in usage patterns with the 1993
      survey were also made. FINDINGS: In 2000, the overall use of at least one
      nonmedically prescribed alternative medicine (excluding calcium, iron, and
      prescribed vitamins) was 52.1% (CI +/- 1.8). Users were more likely to be female,
      be better educated, have a higher income, and be employed. Since 1993, females
      were using significantly more herbal medicines, ginseng, Chinese medicines, and
      aromatherapy oils. Many were self-prescribed. Among users, 57.2% (CI +/- 1.2) did
      not tell their doctor. In 2000, 23.3% of respondents had visited at least one
      alternative practitioner with increasing use of acupuncturists, reflexologists,
      aromatherapists, and herbal therapists. Most thought alternative medicines were
      safe but thought they were, or should be, subject to the same standards as
      prescribed medicines. Among respondents, 92.9% wished product information to be
      of standard and content similar to those supplied with pharmaceuticals.
      INTERPRETATION: Extrapolation of the costs to the Australian population gives an
      expenditure on alternative therapies in 2000 of $AUD2.3 billion and for the U.S.
      population an annual expenditure of $US34 billion. In Australia this represents a
      120 and 62% increase in the cost of alternative medicines and therapists,
      respectively, since 1993. In 2000 expenditure on alternative therapies was nearly
      four times the public contribution to all pharmaceuticals. The public appears to
      have ambivalent standards for alternative therapies but wishes to be empowered
      with accurate information to facilitate self-prescription. The public health
      ramifications of an expanding alternative medicine industry are great.

PMID- 12200103
TI  - Sociodemographic variations in breast cancer screening behavior among Australian
      women: results from the 1995 National Health Survey.
AB  - BACKGROUND: Knowledge of sociodemographic variations in breast cancer screening
      can help identify population groups that are at risk of underutilization of
      breast cancer screening procedures and practices. We examined sociodemographic
      variations in breast cancer screening behavior among Australian women. METHODS:
      We used a subsample of women aged 18 years and older (n = 10,179) from the 1995
      National Health Survey. We examined the association of sociodemographic variables
      with mammography, clinical breast examination, and breast self-examination.
      RESULTS: Being in the oldest age group, never being or previously being married,
      living in rural regions (except in the case of breast self-examination), residing
      in more disadvantaged areas (except in the case of breast self-examination), and
      having lower levels of education were all associated with a smaller likelihood of
      screening. Ethnicity was also significantly associated with screening.
      CONCLUSION: Strategies to promote breast cancer screening practices should pay
      particular attention to the underserved groups and should be part of a more
      comprehensive policy that ensures the accessibility to regular health care of
      these population groups.

PMID- 12200104
TI  - A minimal-contact intervention for cardiac inpatients: long-term effects on
      smoking cessation.
AB  - BACKGROUND: This study examined the 1-year effects of a minimal-contact smoking
      cessation intervention for cardiac inpatients. METHODS: The multicenter study
      included cardiac inpatients who had smoked prior to hospitalization. A pretest
      posttest quasi-experimental design was used. Patients' experimental condition
      depended on the hospital they were assigned to. The design was partially
      randomized: 4 of the 11 hospitals selected the experimental condition themselves
      (2 experimental, 2 control), while the remaining 7 hospitals were randomly
      assigned. The experimental group consisted of patients of 5 hospitals (N = 388).
      Patients of 6 other hospitals served as the control group (N = 401). The
      intervention included stop-smoking advice by the cardiologist, brief counseling
      by the nurse, the provision of self-help materials, and aftercare by the
      cardiologist. RESULTS: Logistic regression analyses controlling for baseline
      differences and covariates did not show significant intervention effects on point
      prevalence and continuous abstinence. The study also showed that the outcomes
      were not significantly related to the way hospitals were assigned to the
      experimental condition. CONCLUSIONS: While short-term effects were found, the
      minimal-contact intervention did not result in significant effects after 12
      months, at least if patients lost to follow-up were treated as posttest smokers.
      Efforts should be made to improve the intervention, especially the aftercare.

PMID- 12200105
TI  - Psychosocial correlates of alternate tobacco product use during early
      adolescence.
AB  - BACKGROUND: The objective was to assess psychosocial correlates of alternate
      tobacco product (chew/snuff, cigar, pipe, bidi, kretek) use. METHODS: Measures of
      alternate tobacco product use, cigarette smoking, environmental smoking exposure,
      and depression were included in a school-based self-report survey completed by
      1,107 ninth graders. RESULTS: The current (past 30 days) use rate for one or more
      alternate tobacco products was 8.3% and the current use rate for cigarettes was
      11%; 45% of current cigarette smokers also used alternate tobacco products. After
      controlling for demographic factors and current cigarette smoking, adolescents
      exposed to peers who smoke and those with greater depressive symptoms were two to
      three times more likely to currently use an alternate tobacco product than
      adolescents without exposure to peer smoking and those with lesser depressive
      symptoms. CONCLUSIONS: Social and psychological associations with alternate
      tobacco product use should be further evaluated as this information could be
      helpful in developing anti-tobacco messages targeted to high-risk youth.

PMID- 12200106
TI  - Anticytokine treatment prevents the increase in the activity of ATP-ubiquitin-
      and Ca(2+)-dependent proteolytic systems in the muscle of tumour-bearing rats.
AB  - The ascites hepatoma Yoshida AH-130 induces loss of body weight and tissue waste.
      Tumour necrosis factor alpha (TNF-alpha) plays a pivotal role in the pathogenesis
      of muscle wasting in this model system, but other cytokines, such as interleukin
      6, may be involved. In order to verify whether a combined anticytokine treatment
      may synergistically counteract muscle protein degradation, tumour bearing rats
      were treated with pentoxyfilline (PTX, an inhibitor of TNF-alpha synthesis), or
      with suramin (SUR, an antiprotozoal drug blocking the peripheral action of
      several cytokines including IL-6 and TNF-alpha), or both the drugs, and the
      effects on muscle proteolytic systems were assessed. Muscle protein loss in the
      AH-130-bearing rats was associated with increased activity of both the ATP
      ubiquitin- and the calpain- dependent proteolytic pathways (246% and 230% of
      controls, respectively). Both PTX and SUR, either alone or in combination,
      prevented the depletion of muscle mass and significantly reduced the activity of
      muscle proteolytic systems. In particular, treatment with SUR, either alone or
      with PTX, induced a decrease in enzymatic activities to values similar to those
      of controls. The results obtained in the present paper demonstrate that: (i)
      muscle depletion in this model is indeed associated with increased proteasome-
      and calpain-dependent proteolysis, as previously suggested by increased mRNA
      expression of molecules pertaining to both pathways; (ii) anticytokine treatments
      effectively reduce muscle protein loss by down-regulating the activity of at
      least two major proteolitic systems; (iii) SUR is more effective than PTX in
      reducing the activity of proteolytic systems, possibly because of its multiple
      anticytokine action.

PMID- 12200108
TI  - Regulation of bronchoalveolar macrophage proinflammatory cytokine production by
      dexamethasone and granulocyte-macrophage colony-stimulating factor after
      stimulation by Aspergillus conidia or lipopolysaccharide.
AB  - There is substantial evidence that local production of proinflammatory cytokines
      are very important in host resistance to aspergillosis. Dexamethasone (DEX) down
      regulates production of these cytokines by stimulated bronchoalveolar macrophages
      (BAM) and constitutes a risk factor for aspergillosis. Granulocyte-macrophage
      colony-stimulating factor (GM-CSF) antagonizes DEX suppression of antifungal
      activity by BAM. Here we investigated the possibility that GM-CSF could
      antagonize DEX down-regulation of interleukin (IL)-1alpha and tumour necrosis
      factor (TNF)-alpha production by stimulated BAM. Control BAM responded to
      increasing numbers of conidia of Aspergillus fumigatus with increasing production
      of IL-1 and TNF. DEX (10(-7)M) significantly suppressed IL-1 and TNF production
      by BAM+conidia. Although GM-CSF did not enhance IL-1 or TNF production by
      BAM+conidia, GM-CSF significantly antagonized DEX suppression of IL-1 cytokine
      production. For comparative purposes, lipopolysaccharide (LPS, 1 microg/ml) was
      used to stimulate BAM in experiments similar to the above. In contrast to the
      findings with conidia, GM-CSF enhanced the production of IL-1 (5-fold) and TNF
      (1.5-fold) by LPS treated BAM. DEX suppression of cytokine production by BAM+LPS
      was modestly but significantly antagonized by GM-CSF. Moreover, differences
      between regulation of IL-1 and TNF production by BAM+conidia or LPS and
      peritoneal macrophages (PM)+conidia or LPS were documented. Finally, the anti
      inflammatory cytokine IL-10 was minimally produced by BAM + conidia or LPS, but
      IL-10 was produced by PM + conidia or LPS. In summary, these data indicate that
      the risk factor for aspergillosis associated with DEX could be lessened in the
      pulmonary compartment with GM-CSF. On the other hand, desired effects of DEX
      could be maintained in other compartments.

PMID- 12200107
TI  - Linked unresponsiveness: early cytokine gene expression profiles in cardiac
      allografts following pretreatment of recipients with bone marrow cells expressing
      donor MHC alloantigen.
AB  - Linked unresponsiveness operates to induce specific unresponsiveness to fully
      mismatched vascularized allografts in recipients pretreated with anti-CD4
      antibody and syngeneic bone marrow cells expressing a single donor MHC class I
      alloantigen. The aim of the study was to evaluate early post transplant cytokine
      expression in allografts where linked unresponsiveness was required for long term
      graft survival. CBA (H2(k)) mice were pretreated with CBK (H2(k)+K(b)) bone
      marrow cells under the cover of anti-CD4 antibody 28 days before transplantation
      of a CBK or a C57BL/10 (H2(b)) cardiac allograft. In both cases graft survival
      was prolonged (MST=100 days). Intragraft expression for interferon (IFN)-gamma,
      interleukin (IL)-2, IL-4, IL-10, IL-12(p40), IL-18, iNOS, transforming growth
      factor (TGF)-beta(1) and C-beta was determined on day 1.5, 3, 7 and 14 after
      transplantation. Whereas rejecting allografts displayed a sharp peak in IFN
      gamma, IL-2, IL-4 and IL-10 expression, non-rejecting allografts were
      characterized by an initial TGF-beta(1) and IFN-gamma production. An increasing
      IL-4 expression towards day 14 was a unique feature of linked unresponsiveness.
      All non-rejecting allografts were characterized by an increasing IL-12(p40)
      production towards day 14. In summary, the early cytokine expression pattern in
      allografts after bone marrow induced operational tolerance is influenced by the
      quantity of donor alloantigens expressed on the graft as well as on the bone
      marrow inoculum.

PMID- 12200109
TI  - Leptin role in advanced lung cancer. A mediator of the acute phase response or a
      marker of the status of nutrition?
AB  - Leptin is an anorexia inductor peptide produced by adipocytes and related to fat
      mass. Leptin is also produced by fat under proinflammatory cytokine action. Our
      objective is to study serum leptin levels in relation to nutritional status and
      acute phase response in advanced-stage non-small cell lung cancer.Seventy-six
      patients newly diagnosed of non surgical non-small cell lung cancer before
      chemotherapy treatment and 30 healthy controls were included. BMI, serum leptin
      and cholesterol levels and lymphocyte count were decreased in lung cancer
      patients. Cytokine IL-6, TNF-alpha, sTNF-RII, sIL-2R, IL-12, IL-10 and IFN-gamma,
      and other acute phase reactants as alpha1 antitrypsin, ferritin, CRP and
      platelets were all raised in patients, whereas the IL-2 was decreased. We found a
      direct relationship between leptin and other indicators of the status of
      nutrition, especially total fat mass. We also found a close relationship between
      the status of nutrition and the performance status (Karnofsky index). However,
      serum leptin and nutritional status were inversely correlated with acute phase
      proteins and proinflammatory cytokines, suggesting a stress-type malnutrition.
      Although serum leptin levels, nutritional status and Karnofsky index are related
      to survival, at multivariate analysis they all were displaced by the acute phase
      reaction markers. These results suggest that cancer anorexia and cachexia are not
      due to a dysregulation of leptin production. Circulating leptin concentrations
      are not elevated in weight-losing cancer patients and are inversely related to
      the intensity of the inflammatory response. In advanced lung cancer patients
      serum leptin concentrations only depend on the total amount of fat.

PMID- 12200110
TI  - Characterisation of the biological activity of recombinant equine eotaxin in
      vitro.
AB  - The chemokine eotaxin (CCL11) is a key player in the trafficking of eosinophils
      to normal tissues and in the tissue eosinophilia associated with human allergic
      disease. We have recently cloned equine eotaxin and here we report the production
      of rEq eotaxin, with and without a C-terminal fusion peptide, in a novel
      expression system utilising stably transfected insect cells. rEq eotaxin induced
      equine eosinophil migration and superoxide production in vitro. A shape change in
      human eosinophils that could be blocked by 7B11, a monoclonal antibody against
      human CCR3, was also observed. Biological activity was not dependent on an intact
      eotaxin C-terminus. These results suggest that equine eotaxin, like its human
      ortholog, may play a role in eosinophil accumulation and activation in the horse.

PMID- 12200111
TI  - Increase of nociceptive threshold induced by intrathecal injection of interleukin
      1beta in normal and carrageenan inflammatory rat.
AB  - The present study was to investigate the effect of intrathecal (i.t.) injection
      of interleukin-1 beta (IL-1 beta) on nociception in normal and inflammatory rats.
      Peripheral inflammation was induced by intraplantar injection (i.pl.) of
      carrageenan into unilateral hind paw. The nociceptive threshold to noxious
      thermal stimulation was measured by the paw withdrawal latency (PWL). Intrathecal
      injection of IL-1 beta (10 ng, 100 ng) significantly increased PWL in normal
      rats, the peak occurred at 5 min and the effect lasted for 30 min. Similarly, IL
      1 beta (10 ng, 100 ng, i.t.) significantly increased the PWL and lasted for more
      than 60 min in inflammatory rats. Both in normal and inflammatory rats, the IL-1
      beta-induced antinociceptive effect was completely abolished by IL-1ra (50 ng,
      i.t.), and apparently attenuated by naloxone (10 microg, i.t.) or mianserin (20
      microg, i.t.). These results suggest that IL-1 beta produces antinociceptive
      effect by binding IL-1 receptor at the spinal level, and is related to the
      activation of opioid and 5-HT systems.

PMID- 12200112
TI  - The expression of the cytomegalovirus chemokine receptor homolog US28 sequesters
      biologically active CC chemokines and alters IL-8 production.
AB  - We hypothesized that US28, a cytomegalovirus (CMV) CC chemokine receptor homolog,
      plays a role in modulating the host antiviral defense. Monocyte chemotaxis was
      induced by supernatants from fibroblasts infected with a US28 deletion mutant of
      CMV (CMV Delta US28) due to endogenously produced CC chemokines MCP-1 and RANTES.
      However, these chemokines were sequestered from the supernatants of CMV-infected
      cells that did express US28. US28 was also capable of sequestering exogenously
      added RANTES. Surprisingly, cells infected with CMV Delta US28 transcribed and
      secreted increased levels IL-8, a CXC chemokine, when compared to CMV-infected
      cells. Finally, because chemokines are potent mediators of immune cell migration
      through the endothelium, we characterized the CC chemokine binding potential of
      CMV-infected endothelial cells. We propose that US28 functions as a 'chemokine
      sink' by sequestering endogenously and exogenously produced chemokines and alters
      the production of the CXC chemokine IL-8, suggesting that CMV could significantly
      alter the inflammatory milieu surrounding infected cells.

PMID- 12200113
TI  - Role of angiotensin II-induced cAMP in mesangial TNF-alpha production.
AB  - Previous findings indicated that cAMP had an inhibitory effect of on tumour
      necrosis factor (TNF)-alpha production. Angiotensin II (Ang II) may activate the
      cAMP-protein kinase A (PKA) pathway in renal mesangial cells through synthesis of
      prostaglandins (PGs) and the possibility arises that inhibition of Ang II-induced
      cAMP formation might result in the overproduction of TNF-alpha in the cell and
      this hypothesis was tested in the present study. Rat mesangial cells were exposed
      to Ang II in the presence or absence of cyclooxygenase inhibitor (indomethacin)
      or cAMP-PKA inhibitor (H-89). Exposure of mesangial cell to Ang II (10(-6)M-10(
      8)M) significantly increased intracellular cAMP level through type 1 Ang II
      receptor but had no effect on TNF-alpha protein release, transcriptional
      activity, or mRNA. However, following the addition of indomethacin or H-89, Ang
      II significantly increased TNF-alpha release, transcriptional activity, and mRNA
      level. These data suggested that in mesangial cells after blockade of cAMP-PKA by
      PG inhibition, Ang II was capable of stimulating TNF-alpha transcription which
      subsequently increased TNF-alpha mRNA accumulation and protein release.

PMID- 12200114
TI  - The --174 G to C polymorphism of interleukin-6 gene is very rare in koreans.
AB  - The proinflammatory cytokine, interleukin-6 (IL-6), seems to be involved in the
      pathogenesis and progression of IgA nephropathy. Moreover, the transcriptional
      activity of the IL-6 gene and the plasma levels of IL-6 protein are associated
      with a single G/C base exchange polymorphism at position -174 of the IL-6 gene
      promoter. Using PCR-RFLP and PCR product sequencing, we examined the -174
      polymorphism in 104 IgA nephropathy patients and in 53 of the normal Korean
      population. Only 2 GC heterozygous variants and no CC homozygous variants were
      found (C allele frequency=0.006). These results suggest that the frequency of the
      C allele in the Korean population is considerably lower than in the Caucasian
      population, and it appears that the -174 G to C polymorphism of IL-6 is very rare
      in Eastern Asians. And, the IL-6 polymorphism at -174 is unlikely to contribute
      significantly to susceptibility to or the progression of IgA nephropathy in
      Koreans.

PMID- 12200115
TI  - Diaphorase catalyzed biotransformation of RDX via N-denitration mechanism.
AB  - Previously, we hypothesized that hexahydro-1,3,5-trinitro-1,3,5-triazine (RDX)
      can be biotransformed by anaerobic sludge via three different routes: (1) direct
      ring cleavage via alpha-hydroxylation of a-CH(2) group, (2) reduction of one of
      the -NO(2) groups to -NO, (3) N-denitration prior to ring cleavage. The present
      study describes biotransformation of RDX via route 3 by a diaphorase (EC 1.8.1.4)
      from Clostridium kluyveri using NADH as electron donor. The removal of RDX was
      accompanied by the formation and accumulation of nitrite ion (NO(2)(-)),
      formaldehyde (HCHO), ammonium (NH(4)(+)), and nitrous oxide (N(2)O). None of the
      RDX-nitroso products were detected. The ring cleavage product
      methylenedinitramine was detected as the transient intermediate. Product
      stoichiometry showed that each reacted RDX molecule produced one nitrite ion and
      the product distribution gave a carbon (C) and nitrogen (N) mass balance of 91
      and 92%, respectively, supporting the occurrence of a mono-denitration step prior
      to the ring cleavage and decomposition. Severe oxygen mediated inhibition (92%
      inhibition) of RDX biotransformation and superoxide dismutase-sensitive
      cytochrome c reduction indicated the potential involvement of an anion radical
      RDX(.-) prior to denitration. A comparative study between native- and apo-enzymes
      showed the possible involvement of flavin mononucleotide (FMN) in catalyzing the
      transfer of a redox equivalent (e/H(+)) from NADH to RDX to produce RDX(.-)
      responsible for secondary decomposition.

PMID- 12200116
TI  - Identification of the functional elements in the bidirectional promoter of the
      mouse O-sialoglycoprotein endopeptidase and APEX nuclease genes.
AB  - The gene for mammalian O-sialoglycoprotein endopeptidase (Osgep) lies immediately
      adjacent to the gene for the APEX nuclease (Apex), a multifunctional DNA repair
      enzyme, in a head-to-head orientation. To clarify the regulation of these
      divergent genes, we studied their promoter regions with luciferase reporters.
      Deletion analysis of a fragment containing the entire mouse Apex gene suggested
      that cis-acting elements driving in the direction of Osgep are widely distributed
      in the mApex gene, in the antisense orientation. We investigated in detail cis
      acting elements near the transcription initiation site of mOsgep. The spacer
      sequence between mOsgep and mApex was shown to have bidirectional promoter
      activity and it has been reported that two CCAAT boxes promote basal
      transcription in the direction of mApex. However, only one of the CCAAT boxes
      proximal to the transcription initiation site of mOsgep was important for
      transcription towards mOsgep. An Sp1-binding sequence was found to be involved in
      bidirectional transcription and a CRE/ATF-like sequence was shown to function as
      a repressor of mOsgep transcription. Quantitative RT-PCR showed that the mApex
      and mOsgep genes were expressed in all tissues examined and that expression of
      mOsgep was low compared with mApex.

PMID- 12200117
TI  - Recombinant adenovirus-mediated p14(ARF) overexpression sensitizes human breast
      cancer cells to cisplatin.
AB  - p14(ARF), the alternative product from the human INK4a/ARF locus, is one of the
      major targets for alterations in the development of human cancers. Overexpression
      of p14(ARF) results in cell cycle arrest and apoptosis. To examine the potential
      therapeutic role of re-expressing p14(ARF) gene product in human breast cancer, a
      recombinant adenovirus expressing the human p14(ARF) cDNA (Adp14(ARF)) was
      constructed and used to infect breast cancer cells. Five days after infection,
      Adp14(ARF) had considerable cytotoxicity on p53-wild-type MCF-7 cells. A time
      course study showed that Adp14(ARF) infection of MCF-7 cells at 100pfu/cell
      increased the number of cells in G0/G1 phase and decreased that in S and G2/M
      phases. The presence of apoptotic cells was confirmed using the TUNEL assay.
      Adp14(ARF)-mediated expression of p14(ARF) also resulted in a considerable
      increase in the amounts of p53 and its target proteins, p21(WAF1) and MDM2.
      Furthermore, the combination treatment of MCF-7 cells with Adp14(ARF) and
      cisplatin resulted in a significantly greater cell death. Together, we conclude
      that p14(ARF) plays an important role in the induction of cell cycle arrest and
      apoptosis in breast cancer cells and recombinant adenovirus-mediated p14(ARF)
      expression greatly increases the sensitivity of these cells to cisplatin. These
      results demonstrate that the proper combination of Adp14(ARF) with conventional
      chemotherapeutic drug(s) could have potential benefits in treating breast cancer
      that carries wild-type p53 gene.

PMID- 12200118
TI  - Specificity of nuclear protein binding to a CYP1A1 negative regulatory element.
AB  - Primary cultures of rat epidermal keratinocytes lose the ability to respond to
      chemicals with the induction of CYP1A1 gene expression after approximately 15
      passages. This repression is mediated by a CT-rich direct repeat negative
      regulatory DNA (NeRD) element present in the upstream regulatory region of the
      CYP1A1 gene. Competitive gel retardation analysis using keratinocyte nuclear
      extracts and mutant NeRD oligonucleotides revealed the presence of two specific
      protein-NeRD complexes and revealed the specific nucleotides important for the
      formation of each complex. These studies demonstrate that these two factors bind
      to overlapping sites within the NeRD element. Nucleotide specificity of complex A
      formation is similar to that of previously identified nuclear silencing factors,
      while that of complex B appears to represent a unique CT-rich binding factor.
      These results suggest that repression of CYP1A1 gene expression in high passage
      keratinocytes may involve the interplay between at least two specific NeRD
      binding factors.

PMID- 12200119
TI  - Synergistic perturbation of phosphatidylcholine/sphingomyelin bilayers by
      diacylglycerol and cholesterol.
AB  - The perturbations induced by second messenger diacylglycerols (DAGs) into bovine
      brain phosphatidylcholine (BBPC) bilayers in the presence or absence of bovine
      brain sphingomyelin (SM) and/or cholesterol were studied by (2)H NMR. Addition of
      15 mol% DAG to BBPC bilayers did not induce non-bilayer lipid phases in the
      temperature range 30-60 degrees C. Similar measurements performed in the presence
      of cholesterol revealed that cholesterol progressively destabilizes PC bilayers
      with respect to DAG-induced perturbations. Thus, at 40 mol% cholesterol, addition
      of 15 mol% DAG induced the formation of non-bilayer (isotropic and inverted
      hexagonal) phases at 60 degrees C. Whereas some lateral separation of the
      bilayers into domains of different cholesterol contents was observed in
      BBPC/cholesterol membranes, such a lateral heterogeneity was greatly facilitated
      by the addition of SM. Since both a tendency to form non-bilayer lipid phases and
      lateral heterogeneity of the membranes are associated with increased activation
      of a number of membrane-associated enzymes, our results suggest that SM- and
      cholesterol-enriched regions of biological membranes (rafts) provide an
      environment with increased sensitivity to the generation of lipid second
      messengers and modified transmembrane signal transduction properties.

PMID- 12200120
TI  - Identification of ubiquitin-like protein-binding subunits of the 26S proteasome.
AB  - Ubiquitin-like proteins Rad23 and Dsk2 have recently been shown to be capable of
      binding both polyubiquitin chains and the 26S proteasome. The ubiquitin-like
      domains (Ubls) of Rad23 and Dsk2 are indispensable for their interaction with the
      26S proteasome, but the proteasome subunits capable of binding the Ubl have not
      been identified. Here, we report that the Ubls of both Rad23 and Dsk2 can bind
      with the 19S regulatory particle (RP) of the 26S proteasome in vivo and in vitro.
      A competition assay using the respective Ubls of Rad23 and Dsk2 revealed that
      they bind to the RP in a competitive manner. The base subcomplex of the RP was
      found to have the ability to bind the Ubl. By cross-linking experiments, Rpn1 and
      Rpn2 were identified as Ubl-binding subunits. Taken together, the results suggest
      that the Rpn1 and Rpn2 in the base subcomplex form the receptor for the ubiquitin
      like protein.

PMID- 12200121
TI  - Polymorphisms of the CYP1B1 gene have higher risk for prostate cancer.
AB  - Various carcinogenic factors including estrogen metabolites play a role in
      malignant transformation. These metabolites are formed in part, as a result of
      the hydroxylation activity of cytochrome P450 (CYP) 1B1. Variant forms of this
      enzyme have been shown to enhance its activity, and thus, we hypothesize that
      single nucleotide polymorphisms of the CYP1B1 gene can be a risk factor for
      prostate cancer. To test this hypothesis, the genetic distribution of six
      different CYP1B1 polymorphisms at intron 1 (C-->T), codon 48 (C-->G), codon 119
      (G-->T), codon 432 (C-->G), codon 449 (C-->T), and codon 453 (A-->G) was analyzed
      in 117 prostate cancer samples and 200 healthy normal subjects from a Japanese
      population. Results of these experiments demonstrate that the genotype at codon
      119 is significantly different between prostate cancer patients and controls
      (P<0.001). The odds ratio of genotype T/T compared to G/G (reference) was
      calculated as 4.02 with a 95% confidence interval of 1.73-9.38. All other codons,
      except 453, showed polymorphisms but were not significantly different between
      cancer patients and controls. No association was found between stage and grade of
      cancer with any of the polymorphic sites. This is the first report that
      demonstrates the polymorphism at codon 119 of CYP1B1 to be associated with
      prostatic carcinogenesis. These results are important in understanding the role
      of CYP1B1 polymorphisms in the pathogenesis of prostate cancer.

PMID- 12200122
TI  - Functional analysis of calcium-binding EF-hand motifs of visinin-like protein-1.
AB  - Visinin-like protein-1 (VILIP-1), a myristoylated calcium sensor protein with
      three EF-hand motifs, modulates adenylyl cyclase activity. It translocates to
      membranes when a postulated "calcium-myristoyl switch" is triggered by calcium
      binding to expose its sequestered myristoyl moiety. We investigated the
      contributions of the EF-hand motifs to the translocation of VILIP-1 to membranes
      and to the modulation of adenylyl cyclase activity. Mutation of residues crucial
      for binding calcium within each one of the EF-hand motifs indicated that they all
      contributed to binding calcium. Simultaneous mutations of all of the three EF
      hand motifs completely abolished VILIP-1's ability to bind calcium, attenuated
      but did not eliminate its modulation of adenylyl cyclase activity, and abolished
      its calcium-dependence for association with cellular membranes. These results
      show that the calcium-binding EF-hand motifs of VILIP-1 do not have an essential
      role in modulating adenylyl cyclase activity but instead have a structural role
      in activating the "calcium-myristoyl switch" of VILIP-1.

PMID- 12200123
TI  - Egg fucose sulfate polymer, sialoglycan, and speract all trigger the sea urchin
      sperm acrosome reaction.
AB  - Macromolecules surrounding eggs induce the acrosome reaction (AR) of spermatozoa.
      In sea urchins, three egg jelly (EJ) molecules: a fucose sulfate polymer (FSP), a
      sialoglycan (SG), and speract mediate ionic fluxes triggering the AR. SG and
      speract are noninductive without FSP. Speract's role in AR induction is
      controversial. Here we show that speract potentiates the FSP-induced AR at pH
      7.0, approximately 1 pH unit lower than natural seawater. At pH 7.0, a mixture of
      FSP, SG, and speract produces the intracellular pH increase necessary for maximum
      AR induction. Each EJ component may mediate a distinct intracellular pH control
      mechanism, and all three may function synergistically to increase the
      intracellular pH permitting AR induction. Speract peptides are an ancient family.
      Although important for activating cyclic nucleotide-mediated pathways in today's
      seawater of pH approximately 8, speract may have been more important in AR
      induction in the paleo-ocean of pH approximately 7.

PMID- 12200124
TI  - A plant histaminase modulates cardiac anaphylactic response in guinea pig.
AB  - The effect of a copper amine oxidase (histaminase) purified from the pea seedling
      as free or immobilized enzyme on the response to specific antigen was studied in
      isolated hearts from actively sensitized guinea pigs. In vitro challenge with the
      specific antigen of hearts from actively sensitized animals evokes a positive
      inotropic and chronotropic effect, a coronary constriction, followed by dilation
      and an increase in the amount of histamine and nitrites, the oxidation product of
      nitric oxide, in the perfusates. In the presence of both forms of histaminases,
      the positive inotropic and chronotropic responses as well as the coronary
      constriction and the release of histamine were fully blocked. The amount of
      nitrites, appearing in the perfusates when anaphylaxis is elicited in the
      presence of both forms of histaminases, is significantly increased, as well as
      nitric oxide synthase activity and cyclic GMP content in cardiac tissue, while
      cardiac calcium overload was significantly prevented. These observations
      demonstrate that the decrease in the anaphylactic release of histamine and the
      subsequent abatement of the cardiac response to antigen can be accounted for by
      the inactivation by histaminase of the released histamine and by a stimulation of
      endogenous nitric oxide production.

PMID- 12200125
TI  - Redox regulation of pro-inflammatory cytokines and IkappaB-alpha/NF-kappaB
      nuclear translocation and activation.
AB  - Reduction-oxidation (redox) state constitutes such a potential signaling
      mechanism for the regulation of an inflammatory signal associated with oxidative
      stress. Exposure of alveolar epithelial cells to ascending DeltapO(2) regimen+/
      reactive oxygen species (ROS)-generating systems induced a dose-dependent release
      of interleukin (IL)-1beta, IL-6, and tumor necrosis factor (TNF)-alpha.
      Similarly, the Escherichia coli-derived lipopolysaccharide-endotoxin (LPS) up
      regulated cytokine biosynthesis in a dose- and time-dependent manner.
      Irreversible inhibition of gamma-glutamylcysteine synthetase, the rate-limiting
      enzyme in the biosynthesis of glutathione (GSH), by L-buthionine-(S,R)
      sulfoximine (BSO), induced the accumulation of ROS and augmented DeltapO(2) and
      LPS-mediated release of cytokines. Analysis of the molecular mechanism implicated
      revealed an inhibitory-kappaB (IkappaB-alpha)/nuclear factor-kappaB (NF-kappaB)
      independent pathway in mediating redox-dependent regulation of inflammatory
      cytokines. BSO stabilized cytosolic IkappaB-alpha and down-regulated its
      phosphorylation, thereby blockading NF-kappaB activation, yet it augmented
      cytokine secretion. Glutathione depletion is associated with the augmentation of
      oxidative stress-mediated inflammatory state in a ROS-dependent mechanism and the
      IkappaB-alpha/NF-kappaB pathway is redox-sensitive but differentially involved in
      regulating redox-dependent regulation of cytokines.

PMID- 12200126
TI  - A novel cell-based scintillation proximity assay for studying protein function
      and activity in vitro using membrane-soluble scintillants.
AB  - Here we describe for the first time a cell-based scintillation proximity assay
      using membrane soluble scintillants (MSS). MSS have a scintillant "head" group
      (2,5-diphenyloxazole) attached to a lipophilic "tail." MSS do not scintillate in
      an aqueous environment in the presence of a radioactive source: however, in a non
      aqueous environment, such as a lipid bilayer (e.g., liposome or cell membrane),
      scintillation does occur. MSS can be incorporated into liposomes. When these MSS
      containing liposomes are fused with the plasma membranes of cells in culture the
      MSS are incorporated into the cell membrane. Radiolabelled molecules in close
      proximity to the cell membrane will then elicit a scintillation signal. This
      system has been used to successfully monitor [(14)C]methionine uptake in HeLa
      cells and may be used in radiochemical and radioligand binding assays either in
      vivo or on microsomal preparations obtained from tissues. This new scintillation
      proximity technology could be readily adapted for high-throughput screening.

PMID- 12200127
TI  - Induced expression of MMP-9 in C6 glioma cells is inhibited by PDGF via a PI 3
      kinase-dependent pathway.
AB  - The involvement of phosphatidylinositol 3 (PI 3)-kinase in the signalling
      pathways leading to MMP-9 expression in glioma cells remains unclear. Here, we
      report that PI 3-kinase inhibits MMP-9 expression induced by either IL-1 or TNF
      alpha in rat C6 glioma cells. Using zymography and semi-quantitative RT-PCR
      analysis, we showed that treatment of C6 cells with wortmannin, an inhibitor of
      PI 3-kinase activity, potentiated the expression of MMP-9 induced by both
      cytokines. In contrast, platelet-derived growth factor (PDGF), an inducer of PI 3
      kinase activity in C6 cells, inhibited IL-1- or TNF-alpha-induced MMP-9
      secretion. Accordingly, this inhibition by PDGF was prevented by wortmannin.
      Furthermore, stable C6 clones over-expressing the dominant-negative form the
      regulatory subunit of PI 3-kinase potentiated the expression of MMP-9 induced by
      IL-1 or TNF-alpha. Taken together, these results suggest that PI 3-kinase may act
      as a negative regulator of MMP-9 expression in C6 glioma cells.

PMID- 12200128
TI  - Interaction of the developmental regulator SALL1 with UBE2I and SUMO-1.
AB  - Mutations in the SALL1 gene on chromosome 16q12.1 cause Townes-Brocks syndrome
      (TBS). This autosomal dominantly inherited disorder is characterized by typical
      malformations of the thumbs, the ears, and the anus, and also commonly affects
      the kidneys and other organ systems. SALL1 has recently been shown to localize to
      chromocenters and other heterochromatin foci in murine fibroblasts and to
      interact with the telomere-repeat-binding factor TRF1/PIN2. Here, we show that
      the ubiquitin-conjugating enzyme 2I (UBE2I), the human homolog of S. cerevisiae
      UBC9, and the small ubiquitin-like modifier-1 (SUMO-1) interact with SALL1 in the
      yeast two-hybrid system. The interaction of SALL1 and UBE2I was confirmed in a
      glutathione S-transferase (GST) pull-down experiment. In an in vitro assay, it
      could be demonstrated that SALL1 is covalently modified by at least two SUMO-1
      molecules in the presence of UBA2/AOS1 and UBE2I. Mutation of lysine 1086 of
      SALL1 to arginine abrogates SALL1 sumoylation, suggesting the presence of a
      polymeric SUMO-1 chain in the wild type state.

PMID- 12200129
TI  - Pigment epithelium-derived factor protects cultured retinal pericytes from
      advanced glycation end product-induced injury through its antioxidative
      properties.
AB  - Pigment epithelium-derived factor (PEDF) has recently been shown to be the most
      potent inhibitor of angiogenesis in the mammalian eye, suggesting that loss of
      PEDF is involved in the pathogenesis of proliferative diabetic retinopathy.
      However, a protective role for PEDF in pericyte loss in early diabetic
      retinopathy remains to be elucidated. In this study, we investigated whether PEDF
      proteins could protect against advanced glycation end product (AGE)-induced
      injury in retinal pericytes. Ligand blot analysis revealed that pericytes
      possessed a membrane protein with binding affinity for PEDF. PEDF proteins were
      found to significantly inhibit AGE-induced reactive oxygen species (ROS)
      generation and the subsequent decrease in DNA synthesis and apoptotic cell death
      in pericytes. Further, PEDF proteins completely restored the down-regulation of
      bcl-2 gene expression in AGE-exposed pericytes. The results demonstrated that
      PEDF proteins protected cultured pericytes from AGE-induced cytotoxicity through
      its anti-oxidative properties. Our present study suggests that substitution of
      PEDF proteins may be a promising strategy in treatment of patients with early
      diabetic retinopathy.

PMID- 12200130
TI  - Loss of oxidized and chlorinated bases in DNA treated with reactive oxygen
      species: implications for assessment of oxidative damage in vivo.
AB  - Oxidative damage to DNA has been reported to occur in a wide variety of disease
      states. The most widely used "marker" for oxidative DNA damage is 8
      hydroxyguanine. However, the use of only one marker has limitations. Exposure of
      calf thymus DNA to an .OH-generating system (CuCl(2), ascorbate, H(2)O(2)) or to
      hypochlorous acid (HOCl), led to the extensive production of multiple oxidized or
      chlorinated DNA base products, as measured by gas chromatography-mass
      spectrometry. The addition of peroxynitrite (ONOO(-)) (<200 microM) or SIN-1
      (1mM) to oxidized DNA led to the extensive loss of 8-hydroxyguanine, 5
      hydroxycytosine, 2,6-diamino-4-hydroxy-5-formamidopyrimidine, 2-hydroxyadenine, 8
      hydroxyadenine, and 4,6-diamino-5-formamidopyrimidine were lost at higher ONOO(-)
      concentrations (>200 microM). Exposure of DNA to HOCl led to the generation of 5
      Cl uracil and 8-Cl adenine and addition of ONOO(-) (<200 microM) or SIN-1 (1mM)
      led to an extensive loss of 8-Cl adenine and a small loss of 5-Cl uracil at
      higher concentrations (>500 microM). An .OH-generating system
      (CuCl(2)/ascorbate/H(2)O(2)) could also destroy these chlorinated species.
      Treatment of oxidized or chlorinated DNA with acidified nitrite (NO(2)(-), pH 3)
      led to substantial loss of various base lesions, in particular 8-OH guanine, 5-OH
      cytosine, thymine glycol, and 8-Cl adenine. Our data indicate the possibility
      that when ONOO(-), nitrite in regions of low pH or .OH are produced at sites of
      inflammation, levels of certain damaged DNA bases could represent an
      underestimate of ongoing DNA damage. This study emphasizes the need to examine
      more than one modified DNA base when assessing the role of reactive species in
      human disease.

PMID- 12200131
TI  - Hypoxia activates beta(1)-integrin via ERK 1/2 and p38 MAP kinase in human
      vascular smooth muscle cells.
AB  - Hypoxia plays an important role in vascular remodeling and directly affects
      vascular smooth muscle cell (VSMC) functions. VSMC adhesion participates in
      changes of vascular structure; however, little is known about VSMC adhesion under
      hypoxic conditions. It was the aim of the present study to investigate the
      effects of hypoxia on adhesion mechanisms in human VSMCs. Compared to normoxic
      cells, hypoxia (1% O(2), 24h) significantly increased adhesion of VSMCs to
      collagen I by 30.2% and fibronectin by 58.0%. This effect was completely
      inhibited in the presence of the pharmacological ERK 1/2 mitogen-activated
      protein kinase (MAPK) pathway inhibitor PD98059 (30 microM) or the p38 MAPK
      inhibitor SB203580 (1 microM). Basal adhesion of normoxic cells was not affected
      by pretreatment with PD98059 and SB203580. Hypoxia induced a time-dependent
      activation of ERK 1/2 and p38 MAPK activation in human VSMCs, which were
      completely abolished by PD98059 or SB203580, respectively. Since adhesion of
      VSMCs to fibronectin and collagen I involves beta(1)-integrin receptors, we used
      a blocking antibody against beta(1)-integrin (P5D2) to examine potential effects
      of hypoxia on beta(1)-integrins. P5D2 significantly reduced VSMC adhesion to
      fibronectin and collagen I in normoxia and hypoxia in a comparable manner;
      however, beta(1)-integrin protein or mRNA levels were not affected by hypoxia. As
      evidenced by flow cytometry, hypoxia induced a activation of beta(1)-integrins by
      exposing an conformationally sensitive epitope on the beta(1)-subunit. These
      results demonstrate that hypoxia enhances adhesion of VSMC on extracellular
      matrix proteins by activating beta(1)-integrin.

PMID- 12200132
TI  - Insertion of an exogenous domain in the adenovirus type 2 fiber globular region.
AB  - Adenoviruses have been used for gene therapy or immunization due to their ability
      to efficiently infect a broad range of cells and tissues. These applications as
      well as specificity could be improved further by redirecting binding of the virus
      to specific cell types. In this regard, modification of viral genes encoding coat
      proteins is an option to achieve improvement in retargeting. In this report, we
      describe a substitution in the adenovirus type 2 fiber globular region by the 44
      amino acid C4 domain of human immunodeficiency virus type 1 gp120. In vitro
      translation analysis and immunoprecipitation assays show that the incorporation
      of the C4 domain into the fiber protein does not ablate its trimerization
      property and demonstrates the availability of the C4 epitope for interaction with
      monoclonal anti-C4 antibody. The recombinant adenovirus containing this modified
      fiber was also characterized by immunoprecipitation with the same antibody,
      showing the viability of such kind of modification.

PMID- 12200133
TI  - Direct binding of plectin to Fer kinase and negative regulation of its catalytic
      activity.
AB  - Plectin is a cyoskeletal linker protein that protects tissues against mechanical
      stress. We report here that the N-terminal domain of the nonreceptor tyrosine
      kinase Fer interacts with N-terminal sequences of plectin. Recombinant protein
      encoded by exon 12-24 of rat plectin bound directly to amino acid 1-329 of murine
      Fer. Using an antiserum prepared to a recombinant N-terminal fragment of Fer
      kinase, plectin was coimmunoprecipitated with Fer from cell lysates of cultured
      mouse fibroblasts. Plectin was shown to partially colocalize with Fer in these
      cells. Upon transfection of full length Fer cDNA into plectin-negative mouse
      fibroblasts, hyperphosphorylation of Fer was observed; hyperphosphorylation was
      strongly reduced when N-terminal Fer deletion mutants were transfected.
      Immunocomplex kinase assays showed that the activity of Fer kinase transfected
      into plectin-negative fibroblasts was increased compared to that transfected into
      wild type cells. We conclude that Fer interacts with plectin and that this
      interaction may serve to negatively regulate Fer's activity.

PMID- 12200134
TI  - Processing of native caspase-14 occurs at an atypical cleavage site in normal
      epidermal differentiation.
AB  - Caspase-14, a cysteinyl aspartate-specific protease expressed during epidermal
      differentiation, is detected exclusively in the cytosolic fraction of epidermis
      as a complex of procaspase-14 together with caspase-14 large and small subunits.
      On non-denaturing protein gels, native caspase-14 has a relative electrophoretic
      mobility of approximately 80kDa, which resolves into caspase-14 proform, large
      and small subunit in SDS-polyacrylamide. Purification of caspase-14 from native
      skin with subsequent N-terminal sequencing of the small subunit and tryptic
      digest analysis of the large subunit revealed an atypical processing site between
      Ile152 and Lys153, which distinguishes it from other caspases described to date
      that are processed at aspartate residues. Expression of caspase-14 in
      heterologous systems results in unprocessed procaspase-14 without generation of
      the large and small subunits that characterize this protein family. However,
      addition of cellular extracts to purified recombinant human caspase-14 generated
      immunoreactive peptides indistinguishable from large and small subunits in skin.
      These data provide evidence for novel processing of caspase-14 suggesting that
      this enzyme has unique mechanisms of regulation during epidermal differentiation.

PMID- 12200135
TI  - Identification of a candidate membrane protein for the basolateral peptide
      transporter of rat small intestine.
AB  - A candidate protein for the basolateral peptide transporter of rat jejunum is
      described. Vascular perfusion of the photoaffinity label, [4-azido-D-phe]-L-ala
      (2.5mM), had no effect on the transepithelial transport of the non-hydrolysable
      dipeptide D-phe-L-gln (1mM) from the lumen, its mucosal accumulation or wash-out
      into the vascular perfusate. When the label was perfused luminally, the
      transepithelial transport of D-phe-L-gln was inhibited by 38% (P<0.001) and
      accumulation increased by 62% (P<0.05). These data are consistent with those of a
      basolateral transporter that is strongly asymmetric in its substrate binding and
      transport properties. Labelling of basolateral membrane vesicles with [4-azido
      3,5-3H-D-phe]-L-ala revealed that the majority of label was incorporated into a
      single protein of M(r)112+/-2 kDa and pI 6.5. MALDI-TOF analysis of tryptic
      digests of the protein followed by database searches established that this
      protein was novel with no obvious similarity to PepT1, the apical membrane
      transporter.

PMID- 12200136
TI  - Intracellular zinc distribution and transport in C6 rat glioma cells.
AB  - In mammalian cells, the intracellular availability of zinc influences numerous
      crucial processes. Its distribution has previously been visualized with several
      fluorescent probes, but it was unclear how these probes are compartmentalized
      within the cell. Here, we show that in C6 cells the zinc-specific probe Zinquin
      is evenly distributed. Thus, the significantly lower level of fluorescence in the
      nucleus and a punctuate vesicular staining are real differences in the
      concentrations of zinc. Chemical perturbation of the steady state by releasing
      intracellular protein-bound zinc with the sulfhydryl-reactive N-ethylmaleimide
      (NEM) resulted in a vanadate sensitive transport of zinc out of the nucleus and
      into zincosomes. If the zinc-release was performed with the histidine-reactive
      diethylpyrocarbonate, sequestration was reduced compared to treatment with NEM,
      indicating the importance of histidine within membrane zinc transporters. Another
      major factor regulating the zinc homeostasis is ion export. As determined by
      atomic absorption spectroscopy, up to 50% of the cellular zinc was exported by a
      mechanism sensitive to lanthanum ions. We conclude that different concentrations
      of labile zinc exist in different cellular compartments, which are maintained by
      export and intracellular transport of zinc.

PMID- 12200137
TI  - IL-2 receptor signaling through the Shb adapter protein in T and NK cells.
AB  - Interleukin-2 induces heterodimerization of the IL-2 receptor beta and gamma
      subunits. This study addresses a role of the Shb adapter protein in IL-2 receptor
      signaling in T and NK cells. The IL-2Rbeta and gamma chains were found to co
      immunoprecipitate with Shb, when each alone was co-expressed with Shb in COS
      cells. Using fusion proteins, the Shb SH2 domain was found to associate in a
      phosphotyrosine-dependent manner with the IL-2 receptor beta and gamma subunits
      upon IL-2 stimulation in primary T cells and the NK cell line NK-92. The main
      binding site of the Shb SH2 domain was phosphorylated Tyr-510 in the IL-2Rbeta
      chain. Shb was also phosphorylated upon IL-2 stimulation when overexpressed
      together with IL-2Rbeta (in pre-B cells, which express the gamma chain
      constitutively). These cells were also less apoptotic in the presence of IL-2
      than cells overexpressing a mutant Shb (with a defect SH2 domain) or cells
      expressing a mutant IL-2Rbeta, with the Shb binding sites mutated to
      phenylalanine (Y392F, Y510F). JAK1 and JAK3 were also found to associate with
      Shb, but in contrast to the Shb-IL-2 receptor association, JAK1 and 3 appear to
      associate with the proline-rich regions of Shb. In conclusion, Shb links the IL-2
      receptor to other signaling proteins and mediates the regulation of apoptosis in
      the presence of IL-2.

PMID- 12200138
TI  - Preconditioning decreases ischemia/reperfusion-induced release and activation of
      matrix metalloproteinase-2.
AB  - Release and activation of matrix metalloproteinases (MMPs) significantly
      contribute to myocardial stunning injury immediately after ischemia and
      reperfusion, however, their role in preconditioning remains unknown. We therefore
      examined the effects of preconditioning and subsequent ischemia/reperfusion on
      MMP activity in isolated rat hearts. Hearts were subjected to a preconditioning
      protocol (three consecutive 5-min periods of global ischemia interspersed with 5
      min of reperfusion) followed by 30 min ischemia and 5 min reperfusion. To measure
      MMP release, coronary effluent was collected: (a) during aerobic perfusion, (b)
      in reperfusion following each preconditioning ischemia, and (c) during the final
      reperfusion following test ischemia. MMP-2 activities could be detected by
      gelatin zymography in the ventricles and coronary effluent samples from the
      perfused hearts. The levels of MMP-2 activity in the effluent were markedly
      increased in effluent following test ischemia from control hearts without
      preconditioning. This was accompanied by a decrease in corresponding tissue MMP
      activities. Preconditioning significantly decreased the MMP-2 activity in the
      coronary effluent following test ischemia/reperfusion and preserved the MMP-2
      protein content and activity in the myocardium. Our results demonstrate that
      classic preconditioning inhibits ischemia/reperfusion induced release and
      activation of MMP-2. These results suggest that preconditioning may exert part of
      its cardioprotective effects through the reduction of MMP-2 release.

PMID- 12200139
TI  - The mechanisms of lipoxygenase inhibitor-induced apoptosis in human breast cancer
      cells.
AB  - Previous experimental studies have shown that high dietary fat intake is
      associated with mammary carcinogenesis. In the current study, the effect of 5-LOX
      or 12-LOX inhibitors on human breast cancer cell proliferation and apoptosis, as
      well as the possible mechanisms were investigated. The LOX inhibitors, NDGA, Rev
      5901, and baicalein all inhibited proliferation and induced apoptosis in MCF-7
      (ER+) and MDA-MB-231 (ER-) breast cancer cell in vitro. In contrast, the LOX
      products, 5-HETE and 12-HETE had mitogenic effects, stimulating the proliferation
      of both cell lines. These inhibitors also induced cytochrome c release, caspase-9
      activation, as well as downstream caspase-3, caspase-7 activation, and PARP
      cleavage. LOX inhibitor treatment also reduced the levels of anti-apoptotic
      proteins Bcl-2 and Mcl-1 and increased the levels of the pro-apoptotic protein
      bax. In conclusion, blockade of both 5-LOX and 12-LOX pathways induces apoptosis
      in breast cancer cells through the cytochrome c release and caspase-9 activation,
      with changes in the levels of Bcl-2 family proteins.

PMID- 12200140
TI  - Supercomplex formation between Mlh1-Mlh3 and Sgs1-Top3 heterocomplexes in meiotic
      yeast cells.
AB  - The genome of Saccharomyces cerevisia encodes four mismatch repair MutL proteins
      and these proteins form three heterocomplexes: Mlh1-Mlh2, Mlh1-Mlh3, and Mlh1
      Pms1. Only, the Mlh1-Mlh3 heterocomplex has been implicated specifically in
      promotion of meiotic crossing-over. In this report, we show that yeast Mlh3 co
      immunoprecipitates with Sgs1 helicase in sporulating cells at late stage of
      meiotic prophase I. Sgs1, a member of the RecQ DNA helicase family, appears to
      form a stable complex with topoisomerase III (Top3) during meiosis. We suggest
      that Mlh1-Mlh3 heterocomplex may act as a molecular matchmaker to coordinate Sgs1
      Top3 complex in the resolution of meiotic recombination intermediates.

PMID- 12200141
TI  - RNA polymerase II large subunit is cleaved by caspases during DNA damage-induced
      apoptosis.
AB  - UV radiation induces DNA lesions that are repaired by the nucleotide excision
      repair (NER) pathway. Cells that are NER deficient such as those derived from
      xeroderma pigmentosum (XP) patients are susceptible to apoptosis after 10J/m(2)
      UV radiation, a dose largely survivable by repair proficient cells. Herein, we
      report that RNA polymerase II large subunit (RNAP II-LS) undergoes caspase
      mediated cleavage, yielding a 140kDa C-terminal fragment in XP lymphoblasts but
      not NER proficient lymphoblasts after 10J/m(2) UV irradiation. Cleavage could
      also be induced by cisplatin or oxaliplatin, but not transplatin, an isomer of
      cisplatin that does not induce DNA adducts. The cleavage of RNAP II-LS was
      blocked by a panel of caspase inhibitors but not by proteasomal inhibitors or
      inhibitors of other proteases. In vitro cleavage with caspase 8 yielded the same
      140kDa RNAP II-LS fragment observed in vivo. Using site-directed mutagenesis, the
      RNAP II-LS cleavage site was localized to an LETD sequence ending at residue
      1339, which is near its C-terminal domain.

PMID- 12200142
TI  - Interaction of oncogenic papillomavirus E6 proteins with fibulin-1.
AB  - Human papillomavirus (HPV) infection is the primary risk factor for the
      development of cervical cancer. The papillomavirus E6 gene is essential for virus
      induced cellular transformation and the viral life cycle. Important insight into
      the mechanism of E6 function came from the discovery that cancer-related HPV E6
      proteins promote the degradation of the tumor suppressor p53. However, mounting
      evidence indicates that interaction with p53 does not mediate all E6 activities.
      To explore the p53-independent functions of E6, we performed a yeast two-hybrid
      screen and identified fibulin-1 as an E6 binding protein. Fibulin-1 is a calcium
      binding plasma and extracellular matrix protein that has been implicated in
      cellular transformation and tumor invasion. The interaction between E6 and
      fibulin-1 was demonstrated by both in vitro and in vivo assays. Fibulin-1 is
      associated specifically with cancer-related HPV E6s and the transforming bovine
      papillomavirus type 1 E6. Significantly, overexpression of fibulin-1 specifically
      inhibited E6-mediated transformation. These results suggest that fibulin-1 plays
      an important role in the biological activities of E6.

PMID- 12200143
TI  - Human brain nucleoside diphosphate kinase activity is decreased in Alzheimer's
      disease and Down syndrome.
AB  - In brain, nucleoside diphosphate kinase (NDPK) and its coding gene, nm23, have
      been implicated to modulate neuronal cell proliferation, differentiation, and
      neurite outgrowth. However, a role of NDPK in neurodegenerative diseases has not
      been reported yet. Using proteomics techniques, we evaluated the protein levels
      of NDPK-A in seven brain regions from patients with Alzheimer's disease (AD) and
      Down syndrome (DS) showing AD-like neuropathology. NDPK-A was significantly
      decreased in brain regions (frontal, occipital, and parietal cortices) of both
      disorders. Due to the limitation of brain samples, the activity of NDPK was
      measured in three brain regions (frontal cortex, temporal cortex, and
      cerebellum). The specific activity of NDPK was significantly decreased in AD
      (frontal cortex) and DS (frontal and temporal cortices). Since NDPK-B could also
      drive the activity of NDPK, protein expression levels of both NDPK-A and NDPK-B
      were studied in frontal cortex by Western blot analysis. NDPK-A was significantly
      decreased in AD, which was consistent with the results of proteomics. However,
      NDPK-A was slightly decreased in DS and protein expression levels of NDPK-B in
      both DS and AD were moderately decreased, without reaching statistical
      significance. We propose that oxidative modification of NDPK could lead to the
      decreased activity of NDPK and, subsequently, influence several neuronal
      functions in neurodegenerative diseases as multifunctional enzyme through several
      mechanisms.

PMID- 12200144
TI  - Effects of nitric oxide donors on vascular endothelial growth factor gene
      induction.
AB  - Nitric oxide (NO) has been reported to modulate the vascular endothelial growth
      factor (VEGF) gene by accumulating hypoxia-inducible factor-1alpha (HIF-1alpha)
      protein, but there is a contradiction among effects of various NO donors. The
      effects of NO donors including S-nitroso-N-acetyl-penicillamine (SNAP), S-nitroso
      glutathione (GSNO), 1-hydroxy-2-oxo-3,3-bis(2-aminoethyl)-1-triazene (NOC18), 3
      [(+/-)-(E)-ethyl-2(')-[(E)-hydroxyimino]-5-nitro-3-hexenecarbamoyl]-pyridine
      (NOR4), 3-morpholinosydnonimine (SIN-1), and nitroprusside (SNP) on the VEGF
      reporter gene were examined. SNAP, GSNO, NOC18, and NOR4 enhanced the VEGF
      reporter activity under normoxia and modulated the hypoxic induction. In
      contrast, SNP had only an inhibitory effect. An NO scavenger attenuated the
      reporter activation by NO donors except NOR4, but did not ameliorate the
      inhibitory effect of SNP. A reducing compound dithiothreitol suppressed NO
      induced activation of the VEGF reporter gene. SNAP, GSNO, and NOC18 induced the
      accumulation of HIF-1alpha protein, while others did not. These results suggest
      that SNAP, GSNO, and NOC compounds are suitable for pharmacological studies in
      HIF-1-mediated VEGF gene activation by NO.

PMID- 12200145
TI  - RecA-promoted sliding of base pairs within DNA repeats: quantitative analysis by
      a slippage assay.
AB  - RecA that catalyses efficient homology search and exchange of DNA bases has to
      effect major transitions in the structure as well as the dynamics of bases within
      RecA-DNA filament. RecA induces slippage of paired strands in poly(dA)-poly(dT)
      duplex using the energy of ATP hydrolysis. Here, we have adopted the targeted
      ligation assay and quantified the strand slippage within a short central cassette
      of (dA)(4)-(dT)(4) duplex. The design offers a stringent test case for scoring a
      cross-talk between A residues with those of T that are diagonally placed on the
      opposite strand at either -3, -2, -1, +1, +2, or +3 pairing frames. As expected,
      the cross-talk levels in RecA mediated as well as thermally annealed duplexes
      were maximal in non-diagonal pairing frame (i.e., 0-frame), the levels of which
      fell off gradually as the frames became more diagonal, i.e., -3<-2<-1 or
      +3<+2<+1. Interestingly, the level of cross-talk in naked duplexes was
      intrinsically less efficient in minus frames than their plus frame counterparts.
      The asymmetry created in naked duplexes by such a disparity between minus versus
      plus frames was partially obviated by RecA. Moreover, RecA promoted a
      significantly higher level of cross-talk selectively in -2 and -1 frames, as
      compared to that in naked DNA, which suggests a model that the elevated cross
      talk in RecA filament may be limited to base pairs housed within the same rather
      than adjacent RecA monomers.

PMID- 12200146
TI  - A designed apoplastocyanin variant that shows reversible folding.
AB  - Plastocyanin, like many other metalloproteins, does not undergo reversible
      folding, which is thought to be due to an irreversible conformational change in
      the copper-binding site. Moreover, apoplastocyanin's ability to adopt a native
      tertiary structure is highly salt-dependent, and even in high salt, it has an
      irreversible thermal denaturation. Here, we report a designed apoplastocyanin
      variant, PCV, that is well folded and has reversible folding in both high and low
      salt conditions. This variant provides a tractable model for understanding and
      designing protein beta-sheets.

PMID- 12200147
TI  - Physical association of the APIS complex and general transcription factors.
AB  - It has recently been demonstrated that a fragment of the proteasome, called the
      APIS complex, plays an important role in RNA polymerase II-mediated
      transcription. Here, it is shown that the APIS complex is physically associated
      with many general transcription factors, including components of yeast FACT
      (Cdc68/Pob3), TFIID, TFIIH, and the RNA polymerase II holoenzyme. Depletion of
      this APIS transcription factor complex from a yeast whole cell extract resulted
      in reduced transcription, indicating that it is functionally relevant. The
      APIS/transcription factor complex does not include detectable levels of the 20S
      proteolytic sub-unit of the proteasome. Furthermore, immunopurified 26S
      proteasome contains little or no transcription factors, suggesting that
      transcription factors and the 20S bind competitively to the APIS complex. These
      data add to the growing body of evidence that the APIS complex has a role in
      transcription, independent of its role in proteolysis and, furthermore, argues
      that it functions in association with the general transcription complex.

PMID- 12200148
TI  - Comparison of antisense oligonucleotides and siRNAs in cell culture and in vivo.
AB  - Efficiencies of a nuclease resistant antisense oligonucleotide and of siRNA both
      being targeted against the green fluorescent protein stably expressed in HeLa
      cells are compared in cell cultures and in xenografted mice. Using Cytofectin GSV
      to deliver both inhibitors, the siRNAs appear to be quantitatively more efficient
      and its effect is lasting for a longer time in cell culture. In mice, we observed
      an activity of siRNAs but not of antisense oligonucleotides. The absence of
      efficiency of antisense oligonucleotides is probably due to their lower
      resistance to nuclease degradation.

PMID- 12200149
TI  - Trichostatin A, a histone deacetylase inhibitor, activates the IGFBP-3 promoter
      by upregulating Sp1 activity in hepatoma cells: alteration of the Sp1/Sp3/HDAC1
      multiprotein complex.
AB  - We determined the molecular mechanisms by which trichostatin A (TSA) induced
      insulin-like growth factor-binding protein 3 (IGFBP-3) gene expression in Hep3B
      cells, a p53-mutant human hepatocellular carcinoma (HCC) cell line. TSA induced
      the expressions of the IGFBP-3 mRNA and protein and the activation of its
      promoter. Using IGFBP-3 promoter deletion constructs, the TSA-responsive element
      was mapped to a region between -115 and -30, relative to the transcription start
      site. Promoter mutation analysis confirmed that the TSA-responsive element
      coincides with the Sp1/GC-rich region on the IGFBP-3 promoter. This
      transcriptional activation appears to be mediated by both the Sp1 and Sp3
      transcription factors and, in particular, by the phosphorylation of Sp1, because
      treatment of Hep3B cells and Schneider (SL2) cells with TSA significantly
      activated phosphorylation of Sp1 in a dose-dependent manner. Consistent with the
      transcriptional activation of the IGFBP-3 promoter by TSA, TSA treatment led to
      the release of HDAC1 and Sp3 from the Sp1 transcriptional factor complex,
      indicating the involvement of multiprotein complexes containing Sp1, Sp3, p300,
      and HDAC-1 in IGFBP-3 activation by TSA. Taken together, these results show that
      Sp1 phosphorylation and the modulation of the Sp1/Sp3/HDAC1 multiprotein complex
      play a pivotal role in the transcriptional activation of the IGFBP-3 promoter
      through the Sp1/GC-rich site by TSA.

PMID- 12200150
TI  - CREB DNA binding activation by a 50-Hz magnetic field in HL60 cells is dependent
      on extra- and intracellular Ca(2+) but not PKA, PKC, ERK, or p38 MAPK.
AB  - To investigate the possible mechanism of gene transcription changes induced by
      magnetic field (MF), we examined the DNA binding behavior of the transcription
      factor cyclic-AMP responsive element binding protein (CREB) in HL60 cells after
      exposure to a 0.1mT 50-Hz extremely low frequency (ELF) sinusoidal MF by a gel
      shift assay. Magnetic field induced a time-dependent activation of CREB binding.
      The complex formation increased shortly after MF exposure for 10min, reaching a
      peak level after 1h, and then recovered to basal level at 4h after exposure. A
      novel MF-induced ATF2/ATF2 homodimer formation was observed after MF exposure for
      30min, 1, and 2h. Furthermore, We found that the MF-induced increase of CREB DNA
      binding in HL60 cells was dependent on both extracellular and intracellular
      Ca(2+) but not PKA, PKC, ERK, or p38 MAPK by using various pathway inhibitors.
      These data indicate that MF exposure activates CREB DNA binding through calcium
      related signal transduction pathways under our experimental conditions.

PMID- 12200151
TI  - Pax-2 interacts with RB and reverses its repression on the promoter of Rig-1, a
      Robo member.
AB  - RB plays dual roles in the regulation of cell proliferation and differentiation.
      The nervous tissue-specific gene Rig-1, a member of the roundabout (Robo)
      guidance receptor family, was identified as an RB-regulated gene in the mouse
      embryo. Herein, we report that a 2.3kb genomic DNA fragment, which contains the
      first 129 bases of the 5'-untranslated region and 2.2kb of the 5'-flanking region
      of Rig-1, has a cell type-specific promoter activity. Rig-1 promoter activity is
      downregulated by RB and upregulated by Pax-2. Furthermore, Rig-1 and Pax-2 mRNAs
      are coexpressed in the hindbrain and spinal cord of the E11.5 mouse embryo,
      suggesting that Pax-2 may regulate Rig-1 expression during the embryonic stage.
      Pax-2 interacts with RB and reverses its transcriptional suppression on the Rig-1
      promoter. In summary, the ubiquitous tumor suppressor RB and the neuron-enriched
      transcription factor Pax-2 may play a role in the regulation of Rig-1 expression
      during embryogenesis.

PMID- 12200152
TI  - Glucocorticoid induced expression of glutamine synthetase in hepatoma cells.
AB  - The enzyme glutamine synthetase (GS) ranks as one of the most remarkable
      glucocorticoid-inducible vertebrate genes. However, little is known about the
      responsible DNA elements and the mode of glucocorticoid action. This is
      especially the case for the induction of GS in hepatoma cells. In the work
      presented, the rat hepatoma cell line FAO was used as a model to study the
      induction of GS under the influence of glucocorticoids. FAO cells do not show GS
      activity in the absence of glucocorticoids and are strongly responding to their
      presence. Analyzing sequences of several thousand base pairs upstream and
      downstream from the transcriptional start point of the GS gene, a glucocorticoid
      responsible element was identified within the first intron of the gene. However,
      evidence is presented that aside from a primary effect on transcription
      glucocorticoids mediate their effect on the expression of GS also at the
      posttranscriptional level.

PMID- 12200153
TI  - Differentiation and gene regulation: toward a holistic understanding of animal
      development: intercellular communication and transcriptional regulation are two
      sides of the same coin.

PMID- 12200154
TI  - Hedgehog signal transduction: recent findings.
AB  - The Hedgehog (Hh) family of signaling molecules are key agents in patterning
      numerous types of tissues. Mutations in Hh and its downstream signaling molecules
      are also associated with numerous oncogenic and disease states. Consequently,
      understanding the mechanisms by which Hh signals are transduced is important for
      understanding both development and disease. Recent studies have clarified several
      aspects of Hh signal transduction. Several new Sonic Hedgehog binding partners
      have been identified. Cholesterol and palmitic acid modifications of Hh and Sonic
      hedgehog have been examined in greater detail. Characterization of the
      trafficking patterns of the Patched and Smoothened proteins has demonstrated that
      these two proteins function very differently from the previously established
      models. The Fused kinase has been demonstrated to phosphorylate the kinesin-like
      protein Costal2 and the sites identified, while Cubitus interruptus has been
      shown to be phosphorylated in a hierarchical manner by three different kinases.
      Finally, the interactions, both genetic and physical, between Fused, Costal2,
      Cubitus interruptus, and Suppressor of Fused have been further elucidated.

PMID- 12200155
TI  - Intramembrane proteolysis controls diverse signalling pathways throughout
      evolution.
AB  - Regulated intramembrane proteolysis (RIP) has recently emerged as a conserved
      mechanism for controlling many signalling pathways in both prokaryotes and
      eukaryotes. Although early examples were confined to the activation of membrane
      tethered transcription factors in the cell receiving the signal, recent analysis
      indicates that RIP also regulates the emission of factors involved in
      intercellular communication.

PMID- 12200156
TI  - From head to tail: links between the segmentation clock and antero-posterior
      patterning of the embryo.
AB  - Periodic production of somites along the anteroposterior axis of the vertebrate
      body involves a molecular oscillator, the 'segmentation clock', which can be
      visualized through the periodic activation of genes linked to the Notch pathway.
      Recent findings show that oscillations initiate at gastrula stages and point to a
      role for FGF signaling in positioning the segmental boundaries. This clock also
      controls aspects of spatio-temporal Hox gene activation thus ensuring a perfect
      match between segment boundary position and future regional identity of the
      somites.

PMID- 12200157
TI  - CSL-independent Notch signalling: a checkpoint in cell fate decisions during
      development?
AB  - During development, signalling by members of the Notch family of cell surface
      receptors plays a widespread role in the assignation of cell fates within the
      process of lateral inhibition. This function of Notch is mediated by a well
      established mechanism that relies on a ligand-induced release of the
      intracellular domain of Notch (NICD) and the interaction of this fragment with
      members of the CSL (CBF1, Suppressor of Hairless, Lag-1) family of transcription
      factors within the nucleus. However, there is increasing evidence that Notch can
      signal in CSL-independent modes.

PMID- 12200158
TI  - Signaling and transcriptional control of pituitary development.
AB  - Many common morphogenic, signaling and transcriptional hierarchy themes exist
      with respect to a number of different model systems representing mammalian
      organogenesis. The developing pituitary gland defines a fundamentally ideal
      system for the study and classification of biochemical and molecular events
      associated with biological transitions such as organ and cellular positional
      determination as well as lineage-specific terminal differentiation. Recent
      advances in defining the extrinsic and intrinsic biological cascades behind
      pituitary development have shed light on the crosstalk between signaling
      molecules and transcription factors as well as the combinatorial regulatory codes
      guiding gland maturation. A thorough assessment of these codes is critical to a
      comprehensive understanding of pituitary organogenesis and the mechanisms which
      may go awry during tumorigenesis.

PMID- 12200159
TI  - Signaling and transcriptional control of pancreatic organogenesis.
AB  - The results of several new studies encourage a revision of fundamental hypotheses
      concerning the cellular and molecular mechanisms underlying pancreatic
      morphogenesis and cell differentiation in the embryo. The roles of FGF- and BMP
      signaling indicate a fundamental difference in the induction of the dorsal and
      the ventral pancreatic anlage. Final commitment to the pancreatic fate requires
      the action of several transcriptional regulators including IPF1/PDX1, PBX1 and
      PTF1-P48 after the onset of pancreatic bud formation. Two, largely independent
      endocrine cell lineages develop during the formation of the embryonic pancreas.
      Lineage tracing has begun to refine our understanding of the origins of the
      acinar, ductal and islet cells.

PMID- 12200160
TI  - Developmental regulation of somite derivatives: muscle, cartilage and tendon.
AB  - Recent research has broadened significantly our understanding of how the somite,
      a specialized mesodermal structure found in vertebrate embryos, gives rise to the
      cartilage, muscle and tendon cell lineages. The specification of somite
      derivatives involves the action of patterning signals secreted from adjacent
      tissue combined with the activation, in particular somitic compartments, of genes
      promoting cell lineage specification.

PMID- 12200161
TI  - Motor neuron specification in worms, flies and mice: conserved and 'lost'
      mechanisms.
AB  - Motor neuron differentiation has been studied intensively in both invertebrates
      and vertebrates in recent years. These studies have led to the identification of
      several key regulatory genes acting to generate motor neurons and to specify
      their subclass identities. By comparing findings from Caenorhabditis elegans,
      Drosophila and vertebrate model systems, it is apparent that both evolutionarily
      conserved and non-conserved mechanisms are used.

PMID- 12200162
TI  - Why size matters: altering cell size.
AB  - Several genes involved in growth control have lately been demonstrated to exhibit
      more potent effects on cell size than on cell proliferation. Many of these genes
      direct protein and ribosomal synthesis, highlighting the interdependence between
      cell size and macromolecular content. The failure to maintain normal cell size
      when these genes are deregulated suggests that, in certain contexts, cell growth
      and division are not coupled or coordinated. Several physiological repercussions
      of altering cell size have been identified.

PMID- 12200163
TI  - Cell sorting in animal development: signalling and adhesive mechanisms in the
      formation of tissue boundaries.
AB  - The organisation of the animal body into distinct tissues requires adhesive
      mechanisms that promote and maintain the physical segregation, the sorting, of
      different cell populations. Signals that control differential cell affinities
      across tissue boundaries have been identified, including Hedgehog, Notch, and EGF
      receptor signalling. Further, several examples demonstrate that cell sorting in
      vivo can be driven by Eph/ephrin signalling and by the differential expression of
      cadherins that modulate cell adhesion and motility.

PMID- 12200164
TI  - Slit proteins: molecular guidance cues for cells ranging from neurons to
      leukocytes.
AB  - Recent studies of molecular guidance cues including the Slit family of secreted
      proteins have provided new insights into the mechanisms of cell migration.
      Initially discovered in the nervous system, Slit functions through its receptor,
      Roundabout, and an intracellular signal transduction pathway that includes the
      Abelson kinase, the Enabled protein, GTPase activating proteins and the Rho
      family of small GTPases. Interestingly, Slit also appears to use Roundabout to
      control leukocyte chemotaxis, which occurs in contexts different from neuronal
      migration, suggesting a fundamental conservation of mechanisms guiding the
      migration of distinct types of somatic cells.

PMID- 12200165
TI  - Molecular mechanisms of selector gene function and evolution.
AB  - Selector proteins regulate the formation and identity of animal body regions,
      organs, tissues, and cell types. Recent studies have focused on the regulation of
      the DNA binding and transcriptional regulatory activity of this special class of
      transcription factors. Elucidation of the architecture of selector-regulated
      target gene enhancers and gene networks, and comparative studies of selector
      protein function are providing important insights into the evolution of
      development and morphology.

PMID- 12200166
TI  - Decoding cis-regulatory DNAs in the Drosophila genome.
AB  - Cis-regulatory DNAs control the timing and sites of gene expression during
      metazoan development. Changes in gene expression are responsible for the
      morphological diversification of metazoan body plans. However, traditional
      methods for the identification and characterization of cis-regulatory DNAs are
      tedious. During the past year, computational methods have been used to identify
      novel cis-DNAs within the entire Drosophila genome. These methods change the way
      that cis-DNAs will be analyzed in future studies and offer the promise of
      unraveling complex gene networks.

PMID- 12200168
TI  - Paying attention to reading errors in acquired dyslexia.
AB  - The important role of selective attention in normal reading is illustrated by a
      relatively rare form of acquired dyslexia known as 'attentional dyslexia'.
      Theories of the functional deficit underlying this disorder differ as to the
      locus of the attentional dysfunction. A recent study by Mayall and Humphreys has
      contributed to this debate by studying letter migration errors in an attentional
      dyslexic.

PMID- 12200167
TI  - Prospects for stem cell therapeutics: myths and medicines.
AB  - With common scientific themes and experimental strategies, stem cell biology is
      evolving into a recognizable discipline. Its clinical arm, regenerative medicine,
      is also gaining momentum-invigorated by the potential of stem cells to provide
      treatments for a host of medical conditions that are poorly served by drug
      therapy. But are the expectations for stem cell therapies realistic or
      overstated? In the past year, neurons, insulin-producing cells, and hematopoietic
      stem cells have been generated from embryonic stem cells or cultivated from
      somatic tissues of the adult. These cells have yielded modest and preliminary
      hints of functional reconstitution in animal models. Although encouraging,
      significant hurdles remain before the promise of stem cells will be realized in
      the clinic.

PMID- 12200170
TI  - Musical minds.
AB  - Music might be described as just a special form of noise, but evidence is
      accumulating to show that listening to it can lead to pronounced physiological
      and emotional responses. In a recent article, Trainor et al. have shown that
      specific aspects of musical structure are processed automatically in the human
      brain, raising the question of whether our response to music has specifically
      evolved or merely occurs as a side-effect of neural architecture.

PMID- 12200169
TI  - Decision-making deficits in drug addiction.
AB  - Core aspects of addictive behaviour can be explained in terms of abnormal
      decision-making. Using recording of autonomic function during performance of two
      gambling tasks, Bechara et al. have recently identified three distinct
      neuropsychological subtypes in individuals with substance dependence. These
      subtypes may reflect dissociable patterns of disruption in limbic brain
      circuitry.

PMID- 12200171
TI  - Imaging brain in search of mind.
AB  - The fourth annual fMRI Experience was held at the National Institutes of Health
      (NIH), in Bethesda, Maryland, USA, on 3-14 May 2002. The conference was organized
      jointly by research fellows at the NIH and Institute of Psychiatry (IoP) in
      London, and benefited from financial support from the National Institute of
      Mental Health (NIMH) Intramural Research Program, the NIMH Division of Intramural
      Training, and the Guarantors of Brain in association with the IoP.

PMID- 12200172
TI  - Genuine imitation.

PMID- 12200173
TI  - Lateral bias in chimpanzee expressions of facial emotion.

PMID- 12200174
TI  - In Briefs.

PMID- 12200175
TI  - Establishing a legitimate relationship with introspection. Response to Jack and
      Roepstorff.

PMID- 12200176
TI  - The 'measurement problem' for experience: damaging flaw or intriguing puzzle?.
      Response to Schooler.

PMID- 12200177
TI  - How can we share experiences?. Comment from Chris Frith.

PMID- 12200178
TI  - Experimenting with introspection. Comment from Shaun Gallagher.

PMID- 12200179
TI  - Human spatial representation: insights from animals.
AB  - HUMAN NAVIGATION IS SPECIAL: we use geographic maps to capture a world far beyond
      our unaided locomotion. In consequence, human navigation is widely thought to
      depend on internalized versions of these maps - enduring, geocentric 'cognitive
      maps' capturing diverse information about the environment. Contrary to this view,
      we argue that human navigation is best studied in relation to research on
      navigating animals as humble as ants. This research provides evidence that
      animals, including humans, navigate primarily by representations that are
      momentary rather than enduring, egocentric rather than geocentric, and limited in
      the environmental information that they capture. Uniquely human forms of
      navigation build on these representations.

PMID- 12200180
TI  - Depth of processing in language comprehension: not noticing the evidence.
AB  - The study of processes underlying the interpretation of language often produces
      evidence that they are complete and occur incrementally. However, computational
      linguistics has shown that interpretations are often effective even if they are
      underspecified. We present evidence that similar underspecified representations
      are used by humans during comprehension, drawing on a scattered and varied
      literature. We also show how linguistic properties of focus, subordination and
      focalization can control depth of processing, leading to underspecified
      representations. Modulation of degrees of specification might provide a way
      forward in the development of models of the processing underlying language
      understanding.

PMID- 12200181
TI  - Neural delays, visual motion and the flash-lag effect.
AB  - In the primate visual system, there is a significant delay in the arrival of
      photoreceptor signals in visual cortical areas. Since Helmholtz, scientists have
      pondered over the implications of these delays for human perception. Do visual
      delays cause the ' position of a moving object to lag its 'real' position? This
      question has recently been re-evaluated in the context of the flash-lag
      phenomenon, in which a flashed object appears to lag behind a moving object, when
      physically the two objects are co-localized at the instant of the flash. This
      article critically examines recent accounts of this phenomenon, assesses its
      biological significance, and offers new hypotheses.

PMID- 12200183
TI  - The Quantum Brain: The Search for the Next Generation of Man.

PMID- 12200182
TI  - New visions of the aging mind and brain.
AB  - Cognitive aging is widely viewed as a process of progressive mental loss.
      Compelling new evidence from functional neuroimaging urges a reconsideration of
      this pessimistic view. In the domains of working memory and episodic memory,
      older adults recruit different brain regions from those recruited by younger
      adults when performing the same tasks. Specifically, older adults show prominent
      changes in the recruitment of prefrontal regions, and a conspicuous increase in
      the extent to which activation patterns are bilateral. These results are
      stimulating new hypotheses about the mechanisms underlying age-related cognitive
      declines and the potential for compensation. By suggesting a life-long potential
      for reorganization and plasticity, these discoveries might revise long-held views
      of functional localization.

PMID- 12200184
TI  - Boot camp for the brain.

PMID- 12200185
TI  - Science in mind.

PMID- 12200186
TI  - Tribute to professor Toshiharu Nagatsu.

PMID- 12200187
TI  - Amine-related neurotoxins in Parkinson's disease: past, present, and future.
AB  - Parkinson's disease (PD) is an aging-related movement disorder caused by a
      deficiency of the neurotransmitter dopamine (DA) in the striatum of the brain as
      a result of selective degeneration of nigrostriatal DA neurons. The molecular
      basis of the cell death of DA neurons is unknown, but one hypothesis is the
      presence of some amine-related neurotoxins that kill specifically nigrostriatal
      DA neurons over a long period of time. This neurotoxin hypothesis of PD started
      in the 1980s when 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) was
      discovered to produce acutely PD-like symptoms. Two groups of natural MPTP-like
      and amine-related neurotoxins have been investigated as endogenous candidate
      compounds: isoquinolines (IQs) and beta-carbolines. These neurotoxins are
      speculated to cause oxidative stress, mitochondrial dysfunction, apoptotic cell
      death, and PD symptoms. However, since PD is a neurodegenerative disorder that
      progresses slowly over a period of many years, a long-term study may be required
      to elucidate the neurotoxicity of such neurotoxins in relation to PD.

PMID- 12200188
TI  - Potential neurotoxic "agents provocateurs" in Parkinson's disease.
AB  - Idiopathic Parkinson's disease (PD), one of the most common neurodegenerative
      disorders associated with aging, is characterized neurochemically by abnormal and
      profound loss of nigrostriatal dopamine (DA) neurons. A prominent current view is
      that the excessive degeneration of the dopaminergic system is the outcome of
      extended insults by environmental neurotoxins or endogenous neurotoxic factors in
      genetically vulnerable or susceptible individuals. Recent insights into the
      identities and mechanisms of potential neurotoxic species, which span pesticides,
      environmental contaminants including heterocyclic amines with beta-carboline
      (betaC) and isoquinoline (IQ) structures, endogenous DA metabolites or
      intermediates, neuromelanin, metals, and infectious agents, are presented.

PMID- 12200189
TI  - Dopamine-derived endogenous N-methyl-(R)-salsolinol: its role in Parkinson's
      disease.
AB  - A dopamine-derived alkaloid, N-methyl-(R)-salsolinol [NM(R)Sal],
      enantioselectively occurs in human brains and accumulates in the nigrostriatal
      system. It increases in the cerebrospinal fluid (CSF) of parkinsonian patients
      and the activity of a neutral (R)-salsolinol [(R)Sal] N-methyltransferase, a key
      enzyme in the biosynthesis of this toxin, increases in the lymphocytes from
      parkinsonian patients, suggesting its involvement in the pathogenesis of
      Parkinson's disease (PD). The studies of animal and cellular models of PD proved
      that this isoquinoline is selectively cytotoxic to dopamine neurons. Using human
      dopaminergic SH-SY5Y cells, NM(R)Sal induces apoptosis by the activation of the
      apoptotic cascade initiated in mitochondria. In this article, we review the
      recent advance in proving our hypothesis that the dopamine-derived neurotoxin
      causes the selective depletion of dopamine neurons in PD.

PMID- 12200190
TI  - N-methylation underlying Parkinson's disease.
AB  - The discovery of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) leads to the
      hypothesis that Parkinson's disease (PD) is maybe initiated or precipitated by
      environmental or endogenous toxins by the mechanism similar to that of MPTP in
      genetically-predisposed individuals. Endogenous analogs of MPTP, such as beta
      carbolines (betaCs) and tetrahydroisoquinolines, have been proposed as possible
      causative candidates causing PD and are bioactivated into potential neurotoxins
      by N-methylation enzyme(s). These N-methylated betaCs and tetrahydroisoquinoline
      have been higher cerebrospinal levels in parkinsonian patients than age-matched
      controls. Thus, there is a hypotheses to influence the pathogenesis of PD, that
      is, the excess enzyme activity to activate neurotoxins, such as N
      methyltransferase, might be higher in PDs. Indeed, simple betaCs, via N
      methylation steps, induced bradykinesia with the decreased dopamine contents in
      the striatum and midbrain in C57/BL mice. In younger (65 years old) PD patients,
      the excretion amount of N(1)-methyl-nicotinamaide was significantly higher than
      that in younger controls. The protein amount of nicotinamide N-methyltransferase
      (NNMT) was also significantly higher in younger PD patients than that in younger
      controls. These findings described here would indicate that the excess N
      methylation ability for azaheterocyclic amines, such as betaCs, before the onset
      had been implicated in PD pathogenesis. On the other hand, the contribution of
      aberrant cytochrome P450 or aldehyde oxidase activity acting on the pyridine
      ring, that could act as detoxification routes of endogenous neurotoxins, would be
      small in the etiology of PD.

PMID- 12200191
TI  - Apoptotic molecules and MPTP-induced cell death.
AB  - MPTP-induced neurotoxicity is one of the experimental models most commonly used
      to study the pathogenesis of Parkinson's disease (PD). MPTP administered in vivo
      to mice causes selective loss of dopaminergic neurons in the substantia nigra
      (SN), as in this disease. Cell death may be induced in vitro by MPP(+), the
      active metabolite of MPTP, when neuronal cell cultures are used. Biochemical
      mechanisms underlying cell death induced by MPTP/MPP(+) still remain to be
      clarified completely. This article reviews some recent findings linking the
      effects of MPTP/MPP(+) with molecules typically involved in apoptotic pathways.
      This type of research has made extensive use of genetically manipulated systems
      such as transgenic mice and transfected cell lines. Evidence has emerged to
      suggest that Bcl-2, Bax, JNK, and caspases are implicated in neurotoxic effects
      due to in vivo MPTP administration to mice. Different neuronal cell lines such as
      MN9D cells, SH-SY5Y cells, cerebellar granule neurons, cortical neurons, and GH3
      cells were also tested to investigate the possible involvement of Bcl-2, Bax, and
      caspases in in vitro MPP(+)-induced neurotoxicity.

PMID- 12200192
TI  - MPTP: insights into parkinsonian neurodegeneration.
AB  - MPTP burst upon the medical landscape two decades ago, first as a mysterious
      parkinsonian epidemic, triggering an unparalleled quest for the toxin's identity,
      and closely followed by an intense pursuit of its cellular mechanisms of action.
      MPTP treatment created an animal model of many features of Parkinson's disease
      (PD), used primarily in primates and later in mice. The critical role of
      oxidative stress damage to vulnerable dopamine neurons, as well as for
      neurodegenerative diseases in general, emerged from MPTP neurotoxicity. A
      remarkable cross-fertilization of basic and clinical findings, including genetic
      and epidemiologic studies, has greatly advanced our understanding of PD and
      revealed multiple factors contributing to the parkinsonian phenotypes. Brain
      imaging localizes sites of action and provides potential presymptomatic
      diagnostic testing. Epidemiologic reports linking PD with pesticide exposure were
      complimented by supportive evidence from biochemical studies of MPTP and
      structurally related compounds, especially after low-level, long-term exposure.
      Genetic studies on the role of risk genes, such as alpha-synuclein or parkin,
      have been validated by biochemical, anatomical and neurochemical investigations
      showing factors interacting to produce pathophysiology in the animal model.
      Focusing on the pivotal role of mitochondria, subcellular pathways participating
      in cell death have been clarified by unraveling similar sites of action of MPTP.
      Along the way, compounds antagonizing or potentiating MPTP effects indicated new
      PD therapies, some of the former achieving clinical trials. The future is
      encouraging for combating PD and will continue to benefit from the MPTP
      neurotoxicity model.

PMID- 12200193
TI  - Influence of neuromelanin on oxidative pathways within the human substantia
      nigra.
AB  - Neuromelanin (NM) is a dark-coloured pigment produced in the dopaminergic neurons
      of the human substantia nigra (SN). The function of NM within the pigmented
      neurons is unknown but other melanins are believed to play a protective role via
      attenuation of free radical damage. Experimental evidence suggests that NM may
      also exhibit this characteristic, possibly by directly inactivating free radical
      species or via its ability to chelate transition metals, such as iron. Increased
      tissue iron, however, may saturate iron-chelating sites on NM and a looser
      association between iron and NM may result in an increased, rather than
      decreased, production of free radical species. The death of NM-pigmented neurons
      in Parkinson's disease (PD) is associated with both a measurable increase in
      tissue iron concentrations and indices of free radical mediated damage,
      suggesting that NM is involved in the aetiology of this disorder. As yet, it is
      unknown whether NM in the parkinsonian brain differs to that found in healthy
      tissue and thus may fulfil a different role within this tissue.

PMID- 12200194
TI  - DOPA causes glutamate release and delayed neuron death by brain ischemia in rats.
AB  - DOPA seems to be a neuromodulator in striata and hippocampal CA1 and a
      neurotransmitter of the primary baroreceptor afferents terminating in the nucleus
      tractus solitarii (NTS) and baroreflex pathways in the caudal ventrolateral
      medulla and rostral ventrolateral medulla in the brainstem of rats. DOPA
      recognition sites differ from dopamine (DA) D(1) and D(2) and ionotropic
      glutamate receptors. Via DOPA sites, DOPA stereoselectively releases by itself
      neuronal glutamate from in vitro and in vivo striata. In the cultured neurons,
      DOPA and DA cause neuron death via autoxidation. In addition, DOPA causes
      autoxidation-irrelevant neuron death via glutamate release. Furthermore, DOPA
      released by four-vessel occlusion seems to be an upstream causal factor for
      glutamate release and resultant delayed neuron death by brain ischemia in striata
      and hippocampal CA1. Glutamate has been regarded as a neurotransmitter of
      baroreflex pathways. Herein, we propose a new pathway that DOPA is a
      neurotransmitter of the primary aortic depressor nerve and glutamate is that of
      secondary neurons in neuronal microcircuits of depressor sites in the NTS. DOPA
      seems to release unmeasurable, but functioning, endogenous glutamate from the
      secondary neurons via DOPA sites. A common following pathway may be ionotropic
      glutamate receptors-nNOS activation-NO production-baroreflex neurotransmission
      and delayed neuron death. However, we are concerned that DOPA therapy may
      accelerate neuronal degeneration process especially at progressive stages of
      Parkinson's disease.

PMID- 12200195
TI  - Manganese-induced apoptosis in PC12 cells.
AB  - Manganese has been known to induce neurological disorders similar to
      parkinsonisms for a long time. Dopamine deficiency has been demonstrated in
      Parkinson's disease and in chronic manganese poisoning, suggesting that the
      mechanisms underlying the neurotoxic effects of the metal ion are related to
      dysfunction of the extrapyramidal system. However, the details of the mechanisms
      have yet to be elucidated. In an effort to learn more about the toxicity of
      manganese, we have employed an in vitro model that uses the PC12
      catecholaminergic cell line. In this model, manganese induces apoptosis in PC12
      cells. In this paper, experiments conducted with this model, the cellular
      biochemical changes, and the mechanism of the cell death are reviewed.

PMID- 12200197
TI  - Aliphatic propargylamines as symptomatic and neuroprotective treatments for
      neurodegenerative diseases.
AB  - Over the past several years, we have developed a number of novel aliphatic
      propargylamine-related compounds. These can be divided into 14 main chemical
      families. These families have been shown to possess members that selectively and
      stereochemically (i.e. R-enantiomer) rescue neurons from p53-dependent apoptosis
      in vitro. In contrast, no rescue has been observed by the enantiomers of the
      opposite configuration or in p53-independent apoptosis. In vivo, several
      compounds have been shown to possess neural rescue properties in models of
      unilateral hypoxia/ischaemia, focal ischaemia, facial nerve axotomy, pmn mice, 1
      methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse and MPTP non-human
      primate. Our prototype compound, R-2HMP, has been shown to be metabolised in a
      manner analogous to that of R-deprenyl but devoid of amphetaminergic metabolites.
      These compounds have been shown to be active through an interaction with the same
      binding site as R-deprenyl and CGP 3466. This site is suggested to be the
      glycolytic enzyme glyceraldehyde-3-phosphate dehydrogenase (GAPDH).

PMID- 12200196
TI  - Physiological role of salsolinol: its hypophysiotrophic function in the
      regulation of pituitary prolactin secretion.
AB  - We have recently observed that 1-methyl-6,7-dihydroxy-1,2,3,4
      tetrahydroisoquinoline (salsolinol) produced by hypothalamic neurons can
      selectively release prolactin from the anterior lobe (AL) of the pituitary gland.
      Moreover, high affinity binding sites for SAL have been detected in areas, like
      median eminence (ME) and the neuro-intermediate lobe (NIL) that are known
      terminal fields of the tuberoinfundibular DAergic (TIDA) and tuberohypophysial
      (THDA)/periventricular (PHDA) DAergic systems of the hypothalamus, respectively.
      However, the in situ biosynthesis and the mechanism of action of SAL are still
      enigmatic, these observations clearly suggest that sites other than the AL might
      be targets of SAL action. Based on our recent observations it may be relevant to
      postulate that an "autosynaptocrine" regulatory mechanism functioning at the
      level of the DAergic terminals localized in both the ME and NIL, may play a role
      in the hypophyseotrophic regulation of PRL secretion. Furthermore, SAL may be a
      key player in these processes. The complete and precise mapping of these intra
      terminal mechanisms should help us to understand the tonic DAerg regulation of
      PRL secretion. Moreover, it may also give insight into the role of pre-synaptic
      processes that most likely have distinct and significant functional as well as
      pathological roles in other brain areas using DAergic neurotransmission, like
      striatonigral and mesolimbic systems.

PMID- 12200198
TI  - Neuroprotection by propargylamines in Parkinson's disease: suppression of
      apoptosis and induction of prosurvival genes.
AB  - In Parkinson's disease (PD), therapies to delay or suppress the progression of
      cell death in nigrostriatal dopamine neurons have been proposed by use of various
      agents. An inhibitor of type B monoamine oxidase (MAO-B), (-)deprenyl
      (selegiline), was reported to have neuroprotective activity, but clinical trials
      failed to confirm it. However, the animal and cellular models of PD proved that
      selegiline protects neurons from cell death. Among selegiline-related
      propargylamines, (R)(+)-N-propargyl-1-aminoindan (rasagiline) was the most
      effective to suppress the cell death in in vivo and in vitro experiments. In this
      paper, the mechanism of the neuroprotection by rasagiline was examined using
      human dopaminergic SH-SY5Y cells against cell death induced by an endogenous
      dopaminergic neurotoxin N-methyl(R)salsolinol (NM(R)Sal). NM(R)Sal induced
      apoptosis (but not necrosis) in SH-SY5Y cells, and the apoptotic cascade was
      initiated by mitochondrial permeability transition (PT) and activated by stepwise
      reactions. Rasagiline prevented the PT in mitochondria directly and also
      indirectly through induction of antiapoptotic Bcl-2 and a neurotrophic factor,
      glial cell line-derived neurotrophic factor (GDNF). Long-term administration of
      propargylamines to rats increased the activities of antioxidative enzymes
      superoxide dismutase (SOD) and catalase in the brain regions containing dopamine
      neurons. Rasagiline and related propargylamines may rescue degenerating dopamine
      neurons through inhibiting death signal transduction initiated by mitochondria
      PT.

PMID- 12200199
TI  - Docosahexaenoic acid attenuated hypertension and vascular dementia in stroke
      prone spontaneously hypertensive rats.

PMID- 12200200
TI  - Diabetic neuropathies in brain are induced by deficiency of BDNF.
AB  - Diabetes is known to be one of the risk factors for dementia; however,
      neuropathic changes in the brain of patients with the disease have not been
      completely revealed. So in the present study, we investigated the brain function
      of rats with diabetes induced by streptozotocin (STZ), one of the most commonly
      used animal models for diabetes. In the diabetic rats, immediately working memory
      performance was impaired in the Y-maze task and neuronal cytoskeleton proteins
      such as calbindin, synaptophysin, and syntaxin were reduced. Furthermore,
      morphological observation by Golgi staining showed a decrease in the number of
      basal dendrites and abnormality of spine structure. Next, we measured the content
      of brain-derived neurotrophic factor (BDNF) in the diabetic brain, because BDNF
      is one of the essential proteins for the maintenance of neuronal functions
      including synapse function and neuronal transmissions. In the diabetic brains,
      both protein and mRNA levels of BDNF were severely reduced. These results suggest
      that, in diabetes, synapse dysfunction is, at least in part, caused by a failure
      of BDNF synthesis in the brain.

PMID- 12200201
TI  - Conformational diseases: misfolding mechanisms may pave the way to early therapy.

PMID- 12200202
TI  - Vasopressin as a target for antidepressant development: an assessment of the
      available evidence.
AB  - Hyperactivity of the hypothalamic-pituitary-adrenal (HPA) axis is one of the key
      biological abnormalities described in major depressive disorder, occurring in 30
      50% of depressed subjects. Corticotropin-releasing hormone (CRH) and vasopressin
      (AVP) are the main regulators of this stress system, with the two neuropeptides
      acting synergistically in bringing about adrenocorticotropin (ACTH) release from
      the anterior pituitary and cortisol from the adrenal gland. Based on the
      demonstration of elevated cerebrospinal fluid levels of CRH in depressives, and
      other evidence, it has been postulated that excess CRH and the resultant
      increased HPA forward drive form the basis of neuroendocrine dysregulation in
      depression. However, there is an accumulating body of evidence to support a
      significant role for AVP in the regulation of pituitary-adrenal activity in
      health and also in depressive disorder. This review, based on a Medline search
      from 1980 to 2001, focuses on the functional neuroanatomy, receptor pharmacology,
      VP synergism with CRH, and the data from clinical and pre-clinical studies that
      support an important role for AVP in the pathophysiology of major depression. We
      suggest that future antidepressants may target the vasopressinergic system.

PMID- 12200203
TI  - Toward validation of atypical depression in the community: results of the Zurich
      cohort study.
AB  - AIMS: This paper (1) examines the validity of the atypical subtype of depression
      in a community-based longitudinal cohort study, (2) presents estimates of the
      prevalence and sex differences of DSM-IV atypical depression and a newly more
      broadly defined atypical syndrome in the community and (3) compares the clinical
      correlates and treatment patterns of those with atypical depression with other
      depressives. METHODS: The Zurich cohort study is comprised of 591 subjects
      selected from a population-based cohort of young adults representative of the
      canton of Zurich in Switzerland, who were screened in 1978 with the Symptom
      Checklist 90-R [L.R. Derogatis (1977)] and followed prospectively with five
      interviews between 1979 and 1993. Atypical depression was defined on a spectrum
      ranging from atypical major to minor to atypical depressive symptoms alone.
      RESULTS: The rate of DSM-IV atypical major depressive episodes in this community
      is 4.8% and for major atypical depression syndrome is 7.3%. Whereas there was no
      marked sex difference for nonatypical features, there was a significant female
      preponderance for DSM-IV and broadly defined atypical depressive subtypes.
      Systematic investigation of the diagnostic criteria for atypical depression
      revealed that a nonhierarchical definition of atypical depression with respect to
      mood reactivity yielded as valid a syndromic definition as the current hierarchy
      based on mood reactivity as an essential feature. Very high comorbidity (odd
      ratios>2.0) was found with seasonality, bipolar II, social phobia, binge eating,
      neurasthenia and sociopathy. LIMITATIONS: Atypical depression was not defined a
      priori, its criteria were derived from two sections of the Zurich interview.
      CONCLUSIONS: Atypical depression has high population prevalence and substantial
      significance in terms of clinical severity, impairment, and service use. The
      intriguing finding that the sex difference in depression may be attributed to
      atypical features of depression will need further investigation. Overall, our
      data indicate that the atypical subtype of depression is a valid entity based on
      evidence from such traditional indicators of validity as inclusion criteria and
      indicators of course. However, there are some problems with discriminatory
      validity from other disorders. Although comorbidity with these disorders may in
      part reflect an operational artifact of symptom overlap, further work needs to be
      done in distinguishing atypical depression from bipolar II.

PMID- 12200204
TI  - Bright-light exposure combined with physical exercise elevates mood.
AB  - BACKGROUND: Physical exercise alleviates depressive symptoms, as does exposure to
      bright light, especially in those with seasonal variation. Our objective was to
      compare the effect of exercise alone or combined with morning bright light on
      mood and the health-related quality of life in healthy subjects. METHODS: Study
      subjects were working-age adults, randomized in two groups (n=80): exercise in
      bright light (group A), or exercise in normal indoor illumination (group B).
      Intervention lasted for 8 weeks and questionnaire data on mood and the health
      related quality of life were collected at study entry, and at weeks 4 and 8.
      RESULTS: Physical exercise both in normal indoor illumination and in bright light
      was effective at alleviating depressive symptoms. The exercise was significantly
      more effective at alleviating so-called atypical depressive symptoms when
      combined with bright-light exposure. LIMITATIONS: There was no active placebo
      condition, but a comparative, randomized trial was executed. CONCLUSIONS:
      Physical exercise in bright light had a positive effect on mood and health
      related quality of life in a sample of healthy, working-age people. Further
      research is needed to explore the mechanisms of the apparent additive effect of
      exercise and light.

PMID- 12200205
TI  - Interpersonal dysfunction in depressed women: impairments independent of
      depressive symptoms.
AB  - BACKGROUND: The study explored the generality of interpersonal impairments in
      depressed women and examined the extent of their independence of current
      depressive episodes or symptoms. METHODS: 812 community women who were formerly
      depressed, currently depressed, or never depressed were compared on a variety of
      indices of interpersonal behavior and beliefs. Information was also obtained from
      their spouses, adolescent children, and raters. Current depressive mood and
      sociodemographic factors that might affect social functioning were controlled.
      RESULTS: Consistent with the hypotheses that interpersonal difficulties are not
      just consequences of depressive symptoms, formerly but not currently depressed
      women were significantly more impaired than never-depressed women on nearly all
      measures. They were less likely to be stably married, had poorer marital
      satisfaction, reported more spouse coercion and physical injury, had more
      problematic relationships with their child, friends, and extended family,
      reported more stressful life events with interpersonal and conflict content, and
      were more insecure in their beliefs about other people. Their spouses and
      boyfriends also reported more problems, and were themselves more likely to have
      diagnosable disorders. However, the groups did not differ in their children's
      perceptions of maternal warmth or hostility. LIMITATIONS: The cross-sectional
      design precluded conclusions about the causal direction of the relationship
      between interpersonal impairment and depressive disorder. Since clinical
      depression is more often than not followed by subthreshold symptoms that are not
      captured by standard diagnostic instruments, such symptoms are not easily
      discernable from preceding or co-existing interpersonal problems. Only women were
      studied. CONCLUSIONS: Interpersonal impairment is a stable feature of depression,
      a significant challenge to treatment, and may reflect underlying vulnerability to
      the onset, and recurrence, of depressive experiences.

PMID- 12200206
TI  - Memory complaints; the association with psycho-affective and health problems and
      the role of personality characteristics. A 6-year follow-up study.
AB  - BACKGROUND: The objective is to investigate whether memory complaints in older
      persons without manifest cognitive decline are associated with depressive
      symptoms, anxiety symptoms, physical health and personality characteristics.
      Furthermore, it is investigated whether personality characteristics have a
      modifying effect on the association of memory complaints with depressive and
      anxiety symptoms and physical health. METHODS: The study was carried out using
      the Longitudinal Aging Study Amsterdam (LASA). Participants were examined during
      three observation cycles covering a period of 6 years. They were asked about
      memory complaints, and were examined on cognitive functioning, physical health,
      depressive and anxiety symptoms, and the personality characteristics: mastery,
      perceived self-efficacy and neuroticism. The data were analysed by means of
      Generalised Estimating Equations (GEE). RESULTS: Memory complaints were
      associated with physical health problems, depressive and anxiety symptoms, low
      feelings of mastery, low perceived self-efficacy and high neuroticism. The
      associations between memory complaints and physical health problems, depressive
      and anxiety symptoms were significantly stronger in people with high mastery,
      high perceived self-efficacy and low neuroticism. LIMITATIONS: We used a
      conservative criterion for cognitive decline and therefore we might have included
      some people with cognitive decline during our follow-up. In order to minimise
      selection bias we included actual cognitive performance in our regression models.
      CONCLUSIONS: Our findings suggest that when older persons complain about their
      memory and do not show actual cognitive decline, one should be aware that these
      complaints might reflect psycho-affective or health problems.

PMID- 12200207
TI  - Al Ain community survey of psychiatric morbidity II. Sex differences in the
      prevalence of depressive disorders.
AB  - AIM: To examine sex differences in the prevalence of depressive disorders in an
      Arab community. METHODS: One thousand three hundred and ninety-four subjects
      (n=1394) were systematically sampled from the general population in Al-Ain city,
      United Arab Emirates. All subjects were interviewed and assessed with the
      modified version of the Composite International Diagnostic Interview (CIDI) and a
      specially designed socio-demographic questionnaire. The lifetime male and female
      prevalence rates were estimated. Multivariate logistic regression of various
      socio-demographic variables was carried out to assess independent risk factors
      for depression. Statistical significance of sex differences in rates of
      depression by various socio-demographic groups were also assessed. RESULTS: The
      lifetime rates in males and females were 2.8 and 10.3%, respectively. F:M ratio
      found in this study is highest reported ratio in the literature. Sex, life
      events, chronic difficulties and to a certain extent age were found to be risk
      factors for depression in the studied community. The prevalence rates of
      depression were higher in females in all above categories but such differences
      reached statistical significance in age category before 55, regardless of marital
      status, when the number of children is four or more and among those exposed to
      recent life events and chronic difficulties. Females were found to to be more
      exposed to chronic life difficulties but only depressed females were
      significantly more subjected to recent life events. CONCLUSION: Sex differences
      in depression is a robust finding but more studies are needed to explain the high
      F:M ratio found in this survey.

PMID- 12200208
TI  - Defining remission by cut off score on the MADRS: selecting the optimal value.
AB  - BACKGROUND: Remission from major depression may be conceptualised in terms of a
      cut-off score on an appropriate rating scale. Candidate values proposed hitherto
      have not been directly validated. METHOD: The relationship between The Clinical
      Global Impression Scale for Severity (CGI-S) and the Montgomery-Asberg Depression
      Rating Scale (MADRS) was explored in 684 major depressed patients (1114
      observations). The value on the MADRS which had greatest concordance with
      remission, as defined by the CGI-S, was computed using two models. Concordance
      between clinician and patient judgements of global illness were also compared.
      RESULTS AND CONCLUSION: The two models yielded optimal definitions of remission
      of <9 and <10 on the MADRS. Either value offers a workable operationalisation of
      remission and there is little to choose between them. CLINICAL RELEVANCE: The
      data confirm that MADRS <10 should provide the clinician with a valid, and
      reasonably objectifiable, target for remission

PMID- 12200209
TI  - The grief experiences and needs of bereaved relatives and friends of older people
      dying through suicide: a descriptive and case-control study.
AB  - BACKGROUND: Little is known about grief experiences of individuals bereaved
      through suicide of older people. Legal procedures may be one source of distress.
      Studies have suggested that guilt feelings, and a sense of rejection, shame or
      stigma, are probably more frequent in relatives bereaved through suicide than in
      those bereaved through other modes of death. METHODS: We examined (a) problems
      experienced during legal procedures after death and (b) grief experiences, in 85
      relatives and friends bereaved through the suicide of person 60 years old or
      over. In a case-control study the bereavement reactions in a subgroup of 46
      people were compared with those of a control group bereaved by the natural death
      of an older person. Interviews, carried out 6-21 months after the deaths,
      included a semi-structured assessment of problems following the death, the Grief
      Experience Questionnaire (GEQ) and the Montgomery and Asberg Depression Rating
      Scale (MADRS). RESULTS: Thirty-six (42.4%) of those bereaved through suicide
      reported problems in their dealings with the coroner's office, and 33 (38.8%)
      described distress caused by media reporting of the inquest. Depression scores
      were similar in the group of individuals bereaved through suicide and those
      bereaved through natural causes. The former scored higher on subscales of the GEQ
      measuring stigmatisation, shame, sense of rejection and "unique reactions"
      compared with those bereaved through natural death. LIMITATIONS: The
      participation rate of potential subjects was somewhat low, especially in the
      control group. Proportions of different kinships to the deceased differed in the
      study and control groups. CONCLUSIONS: Problems in the media reporting of
      coroners' inquests and in inquest procedures are a frequent source of distress
      for bereaved relatives. The common themes of stigma, shame, and sense of
      rejection in bereavement after suicide suggest that these areas should be
      specifically addressed in the counselling of relatives bereaved in this way.

PMID- 12200210
TI  - Early emotional disturbances during nicotine patch therapy in subjects with and
      without a history of depression.
AB  - BACKGROUND: The goal of this study was to compare development of emotional
      symptomatology during smoking cessation with transdermal nicotine patches in
      subjects with and without a history of depression. METHODS: Twenty-five subjects,
      14 with a history of depression and 11 without such a history, were evaluated
      before beginning of cessation, on day 8, day 30, day 90 and day 120. RESULTS AND
      DISCUSSION: On day 120, ten subjects have maintained abstinence: 71.4% of
      subjects with and 45.5% of subjects without a history of depression relapsed.
      Both groups presented variable emotional symptomatology and there was no
      significant differences between subjects with and without a past depression. On
      the other hand, none of the symptoms which emerged during cessation predicted the
      issue of cessation. However, some symptoms appearing before beginning of
      cessation were related to subsequent relapse: lack of pleasure seeking and
      tiredness. Subsequent relapsers also tended to be more tense on baseline. These
      early symptoms can not be considered as withdrawal symptoms, they may reflect
      less confidence in success. It is also suggested that development of anhedonia
      represents an adaptative strategy to prepare for the withdrawal suffering.

PMID- 12200211
TI  - Bipolar depression and melancholia. Comments on Parker et al. 'The nature of
      bipolar depression: implications for the definition of melancholia'. J. Affect.
      Disord. 59 (2000) 217-224.

PMID- 12200213
TI  - Effects of vigabatrin on epileptiform abnormal discharges in hippocampal CA3
      neurons of spontaneously epileptic rats (SER).
AB  - Vigabatrin, a gamma-amino butyric acid (GABA) transaminase inhibitor, is known to
      inhibit partial epilepsy in humans. The spontaneously epileptic rat (SER), a
      double mutant (zi/zi, tm/tm), exhibits both tonic convulsion and absence-like
      seizures from the age of 8 weeks. Hippocampal CA3 pyramidal neurons in SER show a
      long-lasting depolarization shift with accompanying repetitive firing when a
      single stimulus is delivered to the mossy fibers in slice preparations. The
      effects of vigabatrin on the abnormal excitability of hippocampal CA3 pyramidal
      neurons in SER were examined to elucidate the mechanism underlying the
      antiepileptic action of the drug. Intracellular recordings were performed in 24
      hippocampal slice preparations of 20 SER aged 8-17 weeks old. Bath application of
      vigabatrin (1 mM) inhibited the depolarizing shifts with repetitive firing
      induced by mossy fiber stimulation in 15 min without affecting the first spike
      and resting membrane potentials in hippocampal CA3 neurons of SER. A higher dose
      of vigabatrin (10 mM) sometimes inhibited the first spike. However, vigabatrin at
      doses up to 10 mM did not significantly affect the single action potential
      elicited by stimulation of the mossy fibers in the hippocampal CA3 neurons of age
      matched Wistar rats. In addition, application of vigabatrin (10 mM) did not
      significantly affect the firing induced by depolarizing pulse applied in the CA3
      neurons of the SER, nor the miniature excitatory postsynaptic potential (mEPSP)
      recorded in the CA3 neurons of SER. The inhibitory effect of vigabatrin (1 mM) on
      the mossy fiber stimulation-induced depolarization shift with repetitive firing
      was blocked by concomitant application of bicuculline (10 microM), a GABA(A)
      receptor antagonist. These findings strongly suggested that GABA increased by
      inhibition of GABA transaminase with vigabatrin inhibits abnormal excitation of
      hippocampal CA3 neurons of SER via GABA(A) receptors, although the possibility
      that the drug acted directly on the GABA(A) receptors of CA3 neurons could not be
      completely excluded.

PMID- 12200214
TI  - Differences in the use of health services among people with and without epilepsy
      in the United Kingdom: socio-economic and disease-specific determinants.
AB  - We aim to examine the socio-economic, demographic and disease-specific
      determinants in the use of health services by patients with epilepsy, compared to
      people without epilepsy. We used data from the fourth national survey of
      morbidity in general practice, carried out in 1991-1992. Overall mean annual
      number of consultations with general practitioners, home visits and referrals to
      secondary care per person were calculated for people with epilepsy, stratified by
      age, sex and socio-economic status. The proportion of patients consulting for
      certain diseases or disease groups were also calculated for patients with
      epilepsy. Results were compared to these in people without epilepsy, and rate
      ratios were calculated. Patients with epilepsy consulted twice as often, required
      three to four times more home visits, and were referred to secondary care three
      times more often than people without epilepsy, irrespective of age, sex and
      social class. Among patients with epilepsy, consultation rates and home visits
      were higher in females, older people and people from the manual social classes. A
      higher proportion of patients with epilepsy consulted for neoplasms,
      haematological and mental health disorders, dementia, stroke and gastrointestinal
      bleeding. Older age and low social class were less strongly associated with
      health service utilisation than in people without epilepsy, indicating that
      people with epilepsy lose much of the protective effect of young age and high
      social class on health. Factors contributing to the higher utilisation of health
      services in people with epilepsy need to be studied further and their effects
      taken into account in the organisation of health services for people with
      epilepsy.

PMID- 12200215
TI  - Divalproex extended-release versus the original divalproex tablet: results of a
      randomized, crossover study of well-controlled epileptic patients with primary
      generalized seizures.
AB  - PURPOSE: To compare the safety and efficacy of two formulations of divalproex,
      extended-release divalproex versus the original divalproex tablet, in adolescent
      and adult patients with epilepsy. METHODS: Eligible patients were between the
      ages of 12 and 65 years with primary generalized epilepsy, which was controlled
      over the month prior to study enrollment with divalproex or valproic acid 1000 mg
      to 2000 mg/day. The patients were well-controlled; 39 of 43 (91%) had no seizures
      in the previous year. Patients were randomized to receive 84 days of either
      divalproex two times a day (b.i.d.)/three times a day (t.i.d.) or extended
      release divalproex qd and then (crossed over to) 84 days of the comparator
      formulation. During the two treatment periods, patients received the same daily
      dose equivalent of divalproex as was taken during the month prior to study entry.
      The clinical status of patients was evaluated at a screening visit and at four
      subsequent visits conducted every 42 days. RESULTS: There was no statistically
      significant difference between the formulation groups for seizure control rate
      (95% [41/43] for divalproex and 93% [40/43] for extended-release divalproex).
      Likewise, the formulation groups were similar based on the incidence of treatment
      related adverse events. The most frequently reported (< or =11.4% for either
      formulation) treatment-related adverse events were asthenia, tremor, nausea, and
      dizziness. CONCLUSIONS: Extended-release divalproex was similar to divalproex for
      the treatment of well-controlled, primary generalized epilepsy in terms of
      overall safety and efficacy parameters.

PMID- 12200216
TI  - Effects of antiepileptic drugs on induced epileptiform activity in a rat model of
      dysplasia.
AB  - Seizure activity associated with cortical dysplasia (CD) is often resistant to
      standard pharmacologic treatments. Although several animal models exhibit CD,
      virtually nothing is known about antiepileptic drug (AED) responses in these
      animals. Here we have used rats exposed to methylazoxymethanol acetate (MAM) in
      utero, an animal model featuring nodular heterotopia, to investigate the effects
      of AEDs in the dysplastic brain. 4-aminopyridine (100 microM), a K(+) channel
      blocker, was used to induce interictal epileptiform bursting in acute hippocampal
      slices from MAM-exposed and age-matched vehicle-injected control animals.
      Extracellular field recordings were used to monitor seizure activity in vitro.
      Five commonly used AEDs were tested: phenobarbital, 25-400 microM; carbamazepine,
      25-200 microM; valproate (VPA), 0.19-4 mM; ethosuximide (ESM), 0.5-8 mM; and
      lamotrigine (LTG), 49-390 microM. 4-AP-induced bursting occurred with shorter
      latencies in slices from MAM-exposed rats in comparison with slices from
      controls, confirming the intrinsic hyperexcitability of dysplastic tissue. Each
      AED tested demonstrated significant burst suppression in control slices, but
      interictal epileptiform bursting in MAM-exposed slices was resistant to these
      treatments. Even at the highest concentrations, VPA, ESM and LTG had no effect on
      burst amplitude in slices from MAM-exposed rats. Pharmaco-resistance was further
      tested by measuring seizure latencies in awake, freely-moving rats after kainate
      administration (15 mg/kg, i.p.) with and without pre-treatment with VPA (400
      mg/kg i.p.). Pre-treatment with VPA prolonged seizure latency in control rats,
      but had no effect in MAM-exposed animals. These results suggest MAM-exposed rats
      exhibit a dramatically reduced sensitivity to commonly prescribed AEDs.

PMID- 12200217
TI  - Identification and mutational analysis of candidate genes for juvenile myoclonic
      epilepsy on 6p11-p12: LRRC1, GCLC, KIAA0057 and CLIC5.
AB  - Juvenile myoclonic epilepsy (JME) is one of the most frequent hereditary
      epilepsies characterized by myoclonic and tonic-clonic convulsions beginning at 8
      20 years of age. Genetic studies have revealed four major chromosomal loci on
      6p21.3, 6p11-12, 6q24, and 15q14 as candidate regions harboring genes responsible
      for JME. Previously we reported the region on 6p11-p12 (EJM1), and here we report
      the identification and mutational analysis of candidate genes for EJM1. One of
      those is a leucine-rich repeat-containing 1 (LRRC1) gene that is composed of 14
      exons and codes for 524 amino acid residues. In Northern analysis, 7 kb
      transcripts of LRRC1 gene were detected in multiple tissues, most strongly, in
      heart, lung, and kidney. Mutation analysis of LRRC1 gene in 20 JME patients from
      ten families revealed one nucleotide substitution that lead to amino acid
      exchange (c.577 A>G; Ile193Val). This variation, however, did not co-segregate
      with the disease phenotype. We further performed mutational analyses of CLIC5,
      KIAA0057 and GCLC genes in or flank to the EJM1 region. These analyses did not
      provide any evidences that these genes are responsible for the JME phenotype, and
      suggested that these may not be the EJM1 gene.

PMID- 12200218
TI  - Sulthiame in adults with refractory epilepsy and learning disability: an open
      trial.
AB  - This prospective uncontrolled open study explored the efficacy and long-term
      tolerability of sulthiame (STM) in 52 patients with refractory epilepsy and
      learning disability. Thirty-six patients completed a 14-weeks trial period with
      STM and 22 patients achieved a seizure reduction>50% of which three became
      seizure-free. Twenty-six patients continued taking STM for now up to 120 weeks,
      one continued to be seizure-free, whilst five patients stopped STM during this
      period. These promising observations require further evaluation in a controlled
      trial.

PMID- 12200220
TI  - Focal features in patients with idiopathic generalized epilepsy.
AB  - PURPOSE: The stringent dichotomy between focal and generalized epilepsies has
      become a contentious issue, since neuropathological studies as well as structural
      and functional imaging data hypothesized the existence of focal brain
      abnormalities in patients with well-documented idiopathic generalized epilepsy.
      The aim of our study was to investigate whether clinical and EEG features
      generally considered typical for a focal seizure disorder also occur in patients
      with generalized epilepsies to further support the hypothesis of a more
      continuous transition between focal and generalized epilepsies in contrast to the
      present concept of a stringent pathophysiologic dichotomy. METHODS: We
      retrospectively studied 20 consecutive patients with idiopathic generalized
      epilepsy who underwent video EEG monitoring either because of uncertainty of
      their epilepsy syndrome or because of a difficult to treat epilepsy. We
      determined the incidence of (a) focal interictal epileptiform discharges (IEDs),
      (b) intermittent temporal slow waves, and (c) clinical signs that are widely
      accepted as typical for a focal seizure onset, i.e. version, tonic/dystonic
      unilateral posturing, postictal hemiparesis, postictal nose wiping and figure of
      4. RESULTS: Focal IEDs occurred in seven patients (35.0%), intermittent temporal
      slow waves in six (30%), and clinical signs pointing towards a focal seizure
      onset were found in seven patients (35%). CONCLUSION: Our study of EEG and
      clinical data supports the more sophisticated previous investigations in which
      structural and functional imaging as well as histopathological data suggested the
      presence of focal brain abnormalities in patients with 'generalized' epilepsies.
      Furthermore we emphasize the cautious use of isolated focal EEG abnormalities and
      certain clinical signs to prevent a premature diagnosis of focal epilepsy in
      patients who may indeed suffer from a generalized seizure disorder.

PMID- 12200219
TI  - Childhood febrile convulsions--which factors determine the subsequent epilepsy
      syndrome? A retrospective study.
AB  - To analyze the spectrum of epilepsy syndromes which follow childhood febrile
      convulsions (FC) and to examine whether retrospective analysis of clinical
      features of the FC enables discrimination of patients who develop temporal lobe
      epilepsy (TLE) from those who develop generalized epilepsy (GE). One hundred and
      thirteen patients with epilepsy and antecedent FC were retrospectively analyzed.
      We inquired in detail about the clinical characteristics of FC (age, duration,
      number, focal symptoms) as well as family history, birth history, neurological
      status, and psychomotor development before onset of FC. Forty five (39.8%)
      patients had TLE, 41 (36.6%) GE, and 27 (23.9%) had extratemporal epilepsy (ETE).
      Patients with TLE had a significantly longer duration of FC (P< or =0.001), more
      often focal features (P< or =0.001), and febrile status epilepticus (P< or
      =0.001) than patients with GE. Age at FC, Number of FC, family history, birth
      history and neurological status at FC did not differ between groups. A stepwise
      discriminant model allowed correct assignment after cross validation in 84.2% to
      TLE and in 100% to GE. A broad spectrum of epilepsy syndromes follow FC. We found
      a strong association of prolonged and focal FC with later development of TLE.
      Short generalized FC were associated with GE.

PMID- 12200221
TI  - Characterization of pharmacoresistance to benzodiazepines in the rat Li
      pilocarpine model of status epilepticus.
AB  - Status epilepticus is usually initially treated with a benzodiazepine such as
      diazepam. During prolonged seizures, however, patients often lose their
      sensitivity to benzodiazepines, thus developing pharmacoresistant seizures. In
      rats, administration of LiCl followed 20-24 h later by pilocarpine induces a
      continuous, self-sustained, and reproducible form of status epilepticus that can
      be terminated with diazepam when it is administered soon after the pilocarpine
      injection. However, when administered after a 45 min delay, diazepam is less
      effective. Previous findings have suggested that the development of
      pharmacoresistance is related to the stage of status epilepticus. In the present
      study, we characterized the seizure stage-dependence of diazepam
      pharmacoresistance. Following administration of different doses of diazepam at
      varying time intervals after specific behaviorally- and electrographically
      defined seizure stages, stage-, time-, and dose-dependent pharmacoresistance to
      diazepam developed. We also studied two other antiepileptic drugs commonly used
      in the treatment of status epilepticus, phenobarbital and phenytoin. Consistent
      with previous studies, our results indicated a similar relationship between
      stage, time and dose for phenobarbital, but not for phenytoin. Our data are
      consistent with rapid modulation of GABA(A) receptors during status epilepticus
      that may result in pharmacoresistance to antiepileptic drugs that enhance GABA(A)
      receptor-mediated inhibition.

PMID- 12200222
TI  - An anticonvulsant profile of the ketogenic diet in the rat.
AB  - The present study was designed to evaluate the anticonvulsant effects of a high
      fat ketogenic diet (KD) in rats. Animals were maintained on one of four
      experimental diets: (1) calorie-restricted ketogenic (KCR); (2) calorie
      restricted normal (NCR); (3) ad libitum ketogenic (KAL); or (4) ad libitum normal
      (NAL). The calorie-restricted diets were fed in quantities such that they were
      calorically equivalent. All animals began diet treatment at age P37 and each was
      subjected to one of five chemically-induced seizure tests: bicuculline (BIC;
      s.c.), picrotoxin (PIC; s.c.), kainate (KA, i.p. or s.c.) and gamma-butyrolactone
      (GBL, i.p.), strychnine (s.c.). Bipolar epidural electrodes were implanted under
      ketamine/xylazine anesthesia to permit recording the spike and wave discharges
      (SWD) characteristic of electroencephalograms during absence seizures. Ketonemia
      was assayed by measuring blood levels of beta-hydroxybutyrate (BHB)
      spectrophotometrically prior to induction of seizures in each experiment. Animals
      fed ketogenic diets (i.e. either calorie restricted or ad libitum) exhibited
      greater blood levels of BHB compared to control groups. Seizure results show that
      treatment with a KD: (1) reduced the incidence of bicuculline-induced
      convulsions; (2) diminished the number of picrotoxin-induced seizures (KCR group
      only); (3) increased latency to GBL-induced SWD and reduced both the number and
      duration of SWD; but (4) conferred no protection from strychnine-induced
      seizures; and (5) made KA-induced seizures more severe. Together these results
      indicate a spectrum of anticonvulsant action for the KD in rats that includes
      threshold seizures induced via GABA receptors (BIC, PIC, GBL) but not those
      induced at glycine (strychnine) or the KA-subclass of glutamate receptors.
      Uniquely, the KD is the only treatment described that protects against both
      convulsive and non-convulsive (absence) seizures in rats.

PMID- 12200224
TI  - Vasopressin V2 receptor antagonists.
AB  - Hyponatremia, whether due to the syndrome of inappropriate antidiuretic hormone
      secretion (SIADH) or disorders of water retention such as congestive heart
      failure and cirrhosis, is a very common problem encountered in the care of
      medical patients. To date, available treatment modalities for disorders of excess
      arginine vasopressin (AVP) secretion or action have been limited and suboptimal.
      The recent discovery and development of nonpeptide AVP V(2) receptor antagonists
      represents a promising new treatment option to directly antagonize the effects of
      elevated plasma AVP concentrations at the level of the renal collecting ducts. By
      decreasing the water permeability of renal collecting tubules, excretion of
      retained water is promoted, thereby normalizing or improving hypo-osmolar
      hyponatremia. In this review, SIADH and other water retaining disorders are
      briefly discussed, after which the published preclinical and clinical studies of
      several nonpeptide AVP V(2) receptor antagonists are summarized. The likely
      therapeutic indications and potential complications of these compounds are also
      described.

PMID- 12200225
TI  - Pegvisomant: structure and function.
AB  - Pegvisomant is the pegylated form of mutant growth hormone (B2036). B2036 has
      increased affinity in one binding site and lowered affinity in its second binding
      site, it has been shown that this molecule still enables dimerisation of the
      growth hormone receptor at the cell surface but does not allow the necessary
      conformational changes for signalling. Pegylation decreases the antagonistic
      activity of B2036, however the rate of clearance of the pegylated B2036 is
      greatly reduced compared to the unpegylated form. Even though the antagonistic
      activity of pegvisomant is lower than B2036, the reduced rate of clearance makes
      it an effective clinical drug for the treatment of conditions such as acromegaly.

PMID- 12200226
TI  - The search for calcium receptor antagonists (calcilytics).
AB  - The Ca(2+) receptor on the surface of parathyroid cells is the primary molecular
      entity regulating secretion of parathyroid hormone (PTH). Because of this, it is
      a particularly appealing target for new drugs intended to increase or decrease
      circulating levels of PTH. Calcilytic compounds are Ca(2+) receptor antagonists
      which increase the secretion of PTH. The first reported calcilytic compound was
      NPS 2143, an orally active molecule which elicits rapid, 3- to 4-fold increases
      in circulating levels of PTH. These rapid changes in plasma PTH levels are
      sufficient to increase bone turnover in ovariectomized, osteopenic rats. When
      administered together with an antiresorptive agent (estradiol), NPS 2143 causes
      an increase in trabecular bone volume and bone mineral density in osteopenic
      rats. The magnitude of these changes are far in excess of those caused by
      estradiol alone and are comparable with those achieved by daily administration of
      PTH or a peptide analog. These anabolic effects of NPS 2143 on bone are not
      associated with hyperplasia of the parathyroid glands. Calcilytic compounds can
      increase endogenous levels of circulating PTH to an extent that stimulates new
      bone formation. Such compounds could replace the use of exogenous PTH or its
      peptide fragments in treating osteoporosis.

PMID- 12200227
TI  - Quantification of mRNA using real-time reverse transcription PCR (RT-PCR): trends
      and problems.
AB  - The fluorescence-based real-time reverse transcription PCR (RT-PCR) is widely
      used for the quantification of steady-state mRNA levels and is a critical tool
      for basic research, molecular medicine and biotechnology. Assays are easy to
      perform, capable of high throughput, and can combine high sensitivity with
      reliable specificity. The technology is evolving rapidly with the introduction of
      new enzymes, chemistries and instrumentation. However, while real-time RT-PCR
      addresses many of the difficulties inherent in conventional RT-PCR, it has become
      increasingly clear that it engenders new problems that require urgent attention.
      Therefore, in addition to providing a snapshot of the state-of-the-art in real
      time RT-PCR, this review has an additional aim: it will describe and discuss
      critically some of the problems associated with interpreting results that are
      numerical and lend themselves to statistical analysis, yet whose accuracy is
      significantly affected by reagent and operator variability.

PMID- 12200228
TI  - Cloning and characterization of an androgen receptor N-terminal-interacting
      protein with ubiquitin-protein ligase activity.
AB  - The androgen receptor (AR) N-terminal domain plays a critical role in androgen
      responsive gene regulation. A novel AR N-terminal-interacting protein (ARNIP) was
      isolated using the yeast two-hybrid system and its interaction with amino acids
      11-172 of the normal or corresponding region of the polyglutamine-expanded human
      AR confirmed by glutathione S-transferase pulldown assays. ARNIP cDNAs cloned
      from NSC-34 (mouse neuroblastoma/spinal cord) or PC-3 (human prostate
      adenocarcinoma) mRNA encoded highly homologous 30 kDa (261 amino acids) cysteine
      rich proteins with a RING-H2 (C3H2C3 zinc finger) domain; this motif is highly
      conserved in predicted ARNIP-homologous proteins from several other species.
      Expression of the approximately 1.7 kb ARNIP mRNA was detected in various tissues
      by Northern blotting, but was highest in mouse testes, kidney and several
      neuronal cell lines. In addition, the human ARNIP protein was found to be encoded
      by nine exons spanning 32 kb on chromosome 4q21. In COS-1 cells, coexpression of
      ARNIP and AR did not affect AR ligand-binding kinetics, nor did ARNIP act as a
      coactivator or corepressor in transactivation assays. However, AR N-terminal:C
      terminal interaction was reduced in the presence of ARNIP. Intriguingly, ARNIP,
      and in particular its RING-H2 domain, functioned as a ubiquitin-protein ligase in
      vitro in the presence of a specific ubiquitin-conjugating enzyme, Ubc4-1.
      Mutation of a single cysteine residue in the ARNIP RING-H2 domain (Cys145Ala)
      abolished this E3 ubiquitin ligase activity. Fluorescent protein tagging studies
      revealed that AR-ARNIP interaction was hormone-independent in COS-1 cells, and
      suggest that colocalization of both AR and ARNIP to the nucleus upon androgen
      addition may allow ARNIP to play a role in nuclear processes. Thus,
      identification of a novel AR-interacting protein with ubiquitin ligase activity
      will stimulate further investigation into the role of ubiquitination and the
      ubiquitin-proteasome system in AR-mediated cellular functions.

PMID- 12200229
TI  - RXR acts as a coregulator in the regulation of genes of the hypothalamo-pituitary
      axis by thyroid hormone receptors.
AB  - Thyroid hormone receptors (TRs) often modulate transcriptional activity of target
      genes by heterodimerization with the 9-cis retinoic acid receptor (RXR). On
      positive thyroid response elements (TREs), RXR favors binding of the TR-RXR
      complex to DNA and stimulates transcription. RXR action on negative TREs is
      unclear. Furthermore, the single half-site configuration of many negative TREs
      does not favor the binding of a classic TR-RXR heterodimer. In a comparative
      study using CV-1 cells (relatively RXR- and TR-deficient) and JEG-3 cells
      (relatively TR-deficient), we demonstrate the importance of RXR in the negative
      transcriptional regulation of genes of the hypothalamo-pituitary axis by tri
      iodothyronine. While RXR has variable effects on ligand-independent activation
      produced by TRs, it was required for efficient ligand-dependent repression of the
      TRH gene for TRalpha1 and TRbeta1 and of the TSH genes by all TRs. Using
      different RXR constructs we also observed the importance of the C-terminus of RXR
      but not of the N-terminus nor the DNA-binding domain, in the potentiation of
      negative regulation. We thus suggest that, with regard to negative regulation of
      the TRH and TSH genes by thyroid hormones, RXR behaves more like a cofactor than
      a classic heterodimerization partner.

PMID- 12200230
TI  - STAT5 binding contributes to lactational stimulation of promoter III expressing
      the bovine acetyl-CoA carboxylase alpha-encoding gene in the mammary gland.
AB  - Activity of acetyl-CoA carboxylase (ACC)-alpha is rate limiting for de novo
      synthesis of fatty acids. The encoding gene is expressed by three different
      promoters. We characterized promoter III (PIII) from cow, previously only known
      from sheep. Quantitation of transcripts by RNAse protection assays and real time
      PCR revealed that PIII is primarily expressed and strongly induced (
      approximately 28-fold) in the lactating mammary gland. PIII transcripts are
      expressed in mammary epithelial cells (MEC) as shown by in situ hybridization. A
      2999 bp segment of the PIII promoter conferred prolactin and dexamethasone
      inducibility to a luciferase reporter gene in stably transfected mouse MEC cells.
      Lactogenic induction was abolished if a unique signal transducer and activator of
      transcription (STAT)-binding site at position -797 was inactivated by two point
      mutations. An oligonucleotide probe harboring this STAT-site specifically bound
      nuclear proteins from the lactating mammary gland. Binding was abolished by those
      two point mutations and super-shift analyses showed that STAT5A factors are
      present in this complex. Hence, prolactin, acting through STAT5, contributes to
      the activation of ACC expression in the milk producing cells of the lactating
      mammary gland. We discuss that STAT5 might be important in determining the milk
      composition by coordinating fatty acid and protein synthesis during lactation.

PMID- 12200231
TI  - Characterisation of the GH gene cluster in a new-world monkey, the marmoset
      (Callithrix jacchus).
AB  - In most mammals pituitary GH is encoded by a single gene with no close relatives.
      However, in man the GH gene has been shown to be one of a cluster of five closely
      related genes, four of which are expressed in the placenta. Rhesus monkey also
      expresses at least five closely related GH-like genes, although the genomic
      organisation of these has not been fully reported. Here we describe the cloning
      and characterisation of GH-like genes in a new-world monkey, the marmoset
      (Callithrix jacchus). This species possesses a cluster of eight GH-like 'genes'.
      The gene at the 5' end of this cluster encodes pituitary GH and is similar to
      that encoding human GH. Five of the eight marmoset 'genes' are probably
      pseudogenes, since they include mutations which would prevent normal expression,
      including stop codons and small insertions/deletions that would change the
      reading frame. In one case a large part of a gene is deleted, and in another a
      large insertion is introduced into an exon. The remaining two marmoset genes are
      potentially expressible, as proteins with sequences substantially different (at
      25-30% of all residues) from that of marmoset GH itself; whether and in which
      tissue(s) such expression actually occurs is not yet known. None of the marmoset
      genes is clearly equivalent to any of the human GH-like genes expressed in the
      placenta, and this and phylogenetic analysis suggest that the duplications that
      gave rise to the marmoset GH gene cluster occurred independently of those that
      gave rise to the corresponding cluster in man. Although it includes more 'genes',
      the marmoset cluster extends over a shorter region of chromosomal DNA (about 35
      kb) than does the human GH gene cluster (about 50 kb).

PMID- 12200232
TI  - An Ets motif in the proximal decidual prolactin promoter is essential for basal
      gene expression.
AB  - Transcriptional regulation of the prolactin gene in the decidua differs from that
      in the pituitary. Several lines of evidence strongly suggest this difference is
      due to regulation of the prolactin gene in the decidua and other extra-pituitary
      tissues by tissue-specific transcription factors, which activate distinct
      promoters to induce prolactin gene expression in extra-pituitary sites compared
      with the pituitary. The human decidua is a major site of extra-pituitary
      expression of the prolactin gene. Here we present evidence that the transcription
      factor Ets-1 is critical for basal expression of the decidua-type (or decidual)
      prolactin promoter. Overexpression of Ets-1 significantly induces decidual
      prolactin promoter activity in BeWo and JAR cells that express little or no
      endogenous Ets-1. Conversely, a dominant/negative mutant of Ets represses basal
      promoter activity. Although the proximal 1.5 kb of the decidual prolactin
      promoter contains six Ets motifs, only the Ets motif at nt -77/-71 is essential
      for basal gene expression. Mutation of the Ets motif at nt -77/-71 results in an
      approximately 90% decrease in promoter activity, while mutation of the other Ets
      motifs results in only small changes. Electrophoretic mobility shift assays
      demonstrate that Ets proteins in decidualized endometrial stromal cells bind this
      Ets motif in the decidual prolactin promoter. Ets protein expression increases up
      to 20-fold upon induction of decidualization in endometrial stromal cells under
      conditions in which expression of the prolactin gene is also induced. These
      studies provide strong evidence for a critical role of the Ets transcription
      factor in basal expression of the decidual prolactin promoter.

PMID- 12200233
TI  - Biochemical origins of the non-monotonic receptor-mediated dose-response.
AB  - A mathematical model was created to examine how xenobiotic ligands that bind to
      nuclear receptor proteins may affect transcriptional activation of hormone
      regulated genes. The model included binding of the natural ligand (e.g. hormone)
      and xenobiotic ligands to the receptor, binding of the liganded receptor to
      receptor-specific DNA response sequences, binding of co-activator or co-repressor
      proteins (Rp) to the resulting complex, and the consequent transcriptional rate
      relative to that in the absence of the xenobiotic agent. The model predicted that
      the xenobiotic could act as a pure agonist, a pure antagonist, or a mixed agonist
      whose dose-response curve exhibits a local maximum. The response to the agent
      depends on the affinity of the liganded receptor-DNA complex for binding
      additional transcription factors (e.g. co-activator proteins). An inverted U
      shaped dose-response occurred when basal levels of the natural ligand did not
      saturate receptor binding sites and the affinity for co-activator is weaker when
      the xenobiotic ligand is bound to the receptor than when the endogenous ligand is
      bound. The dose-response curve shape was not dependent on the affinity of the
      receptor for the xenobiotic agent; alteration of this value merely shifted the
      curve along the concentration axis. The amount of receptor, the density of DNA
      response sequences, and the affinity of the DNA-bound receptor for Rp determine
      the amplitude of the computed response with little overall change in curve shape.
      This model indicates that a non-monotonic dose-response is a plausible outcome
      for xenobiotic agents that activate nuclear receptors in the same manner as
      natural ligands.

PMID- 12200234
TI  - Estradiol up-regulates estrogen receptor messenger ribonucleic acid in
      endometrial carcinoma (Ishikawa) cells by stabilizing the message.
AB  - Estrogens up-regulate expression of the estrogen receptor alpha (ER) gene in most
      mammalian tissues studied. Using the ovariectomized ewe as a model, we determined
      that estradiol (E(2)) acted post-transcriptionally to increase endometrial ER
      mRNA concentrations by enhancing the stability of the message. The purpose of
      this study was to determine whether a similar E(2) effect occurs in Ishikawa
      cells, a well-differentiated human endometrial adenocarcinoma cell line. The
      presence and function of ER protein in Ishikawa cells was demonstrated by
      transactivation of a transfected plasmid (ERE(2)tkCAT) in response to 10(-)(9) M
      E(2), resulting in a 550% increase in reporter gene RNA. Ishikawa cells also
      responded to E(2) by up-regulating their ER mRNA concentration an average of 100%
      between 7 and 24 h of treatment. The effect of E(2) on ER mRNA stability was
      measured after blocking transcription with actinomycin D to find that the half
      life increased from 6 to 10 h in control and E(2)-treated cells respectively.
      These results are consistent with cell-free studies which showed significant
      enhancement of the half-life of radiolabeled ER 3' untranslated region (3'UTR)
      RNA in extracts from E(2)-treated cells versus those from control cells. Thus,
      Ishikawa cells provide a relevant model system for the study of E(2)-regulated
      endometrial gene expression.

PMID- 12200235
TI  - Response element sequence modulates estrogen receptor alpha and beta affinity and
      activity.
AB  - The relationship between estrogen receptor (ER)-estrogen response element (ERE)
      binding affinity and estradiol (E(2))-induced transcription has not been
      systematically or quantitatively tested. We examined the influence of ERE
      palindrome length and the 3' ERE flanking sequence on ERalpha and ERbeta affinity
      binding in vitro and on the induction of reporter gene activity in transfected
      cells. The addition of one nucleotide in each arm of the 13 bp ERE palindrome,
      forming a 15 bp ERE palindrome, increased ERalpha and ERbeta affinity and
      transcription. In contrast, the addition of an AT-rich flanking sequence from
      genes highly stimulated by E(2) had little effect on affinity or reporter gene
      activity. Notable differences between ERalpha and ERbeta include: both K(d) and
      transcriptional induction were generally higher for ERalpha than ERbeta, better
      correlation between ERE palindrome length and transcriptional induction for
      ERalpha than ERbeta, and a better correlation between (ER-ERE)K(d) and
      transcriptional induction for ERalpha than for ERbeta.

PMID- 12200236
TI  - Constitutive expression of IGF-binding protein-3 by mammary epithelial cells
      alters signaling through Akt and p70S6 kinase.
AB  - IGF-binding protein-3 (IGFBP-3) potentiates IGF-I action in the non-transformed
      mammary epithelial cell line, MAC-T, via a mechanism that is independent of its
      ability to bind IGF-I. The goal of the present study was to determine if IGFBP-3
      might enhance IGF action by influencing intracellular signaling events downstream
      of the IGF receptor. IGF-I stimulated a time-dependent activation of Akt in which
      phosphorylation of Ser(473) was detectable by 1 min and maximal at 15 min. In
      contrast, no activation of extracellular signal-regulated kinase (ERK)1/2 by IGF
      I was observed although basal phosphorylation was readily detectable. In MAC-T
      cells constitutively expressing IGFBP-3 (+BP3), phosphorylation of Akt following
      stimulation with IGF-I was enhanced relative to mock-transfected cells (Mock).
      The enhancement was detectable within 1 min of IGF-I treatment and persisted for
      up to 10 h. The increased phosphorylation observed by Western blotting
      corresponded to a 1.7-fold increase in Akt kinase activity. The enhanced Akt
      response was elicited by factors that activate the IGF receptor but exhibit
      reduced affinity for IGFBP-3, such as Long R(3)IGF-I, B chain IGF-I and insulin.
      In contrast, [Leu(60)]IGF-I, which binds IGFBP-3 but has reduced affinity for the
      IGF receptor, failed to induce comparable activation, suggesting that an
      association between IGF-I and IGFBP-3 is not required for the effect. The
      enhanced Akt activation could not be mimicked by addition of exogenous IGFBP-3.
      Akt phosphorylation was also enhanced by transforming growth factor-alpha in +BP3
      cells, indicating that the effect was not specific to IGF-I. Similar to Akt,
      phosphorylation of p70S6 kinase (p70(S6K)) by IGF-I was also enhanced in +BP3
      cells relative to Mock cells at both 15 min and 10 h. However, this was largely
      an effect of lower basal activation of p70(S6K) in +BP3 cells. These data
      indicate that endogenous IGFBP-3 potentiates IGF action in MAC-T cells by
      enhancing signaling via the phosphatidylinositol 3-kinase pathway at a point that
      is downstream of IGF receptor activation. Further studies will delineate specific
      mechanisms by which IGFBP-3 may influence intracellular events that regulate
      growth in mammary epithelial cells.

PMID- 12200237
TI  - cAMP-dependent transcription of steroidogenic genes in the human adrenal cortex
      requires a dual-specificity phosphatase in addition to protein kinase A.
AB  - Steroid hormone biosynthesis in the adrenal cortex is controlled by the peptide
      hormone adrenocorticotropin (ACTH), which acts to increase intracellular cAMP and
      results in the activation of cAMP-dependent protein kinase A (PKA) and subsequent
      increase in steroidogenic gene transcription. Protein phosphorylation by PKA
      activates transcription of genes encoding steroidogenic enzymes; however the
      precise proteins which are phosphorylated remain to be determined. We have
      recently shown that phosphoprotein phosphatase (PP) activity is essential for
      cAMP-dependent transcription of the human CYP17 (hCYP17) gene in H295R
      adrenocortical cells. The aim of our current studies was to determine if
      inhibition of PP activity attenuates cAMP-dependent mRNA expression of other
      steroidogenic genes in H295R cells. Using various inhibitors of serine/threonine
      and tyrosine PPs, we examined the role of phosphatase activity on cAMP-dependent
      transcription of steroidogenic genes in the adrenal cortex. CYP11A, CYP11B1/2,
      CYP21, and adrenodoxin also require PP activity for cAMP-stimulated gene
      expression. Inhibition of both serine/threonine and tyrosine PP activities
      suppresses the cAMP-dependent mRNA expression of several steroidogenic genes,
      suggesting that a dual-specificity PP is essential for conveying ACTH/cAMP
      stimulated transcription. We propose that PKA phosphorylates and activates a dual
      specificity phosphatase, which mediates steroidogenic gene transcription in
      response to ACTH/cAMP.

PMID- 12200238
TI  - Imaging of appendicitis: a cautionary note.

PMID- 12200239
TI  - Diagnostic value of unenhanced helical CT in adult patients with suspected acute
      appendicitis.
AB  - Clinical diagnosis of appendicitis is usually made on the basis of history,
      physical examination and laboratory studies. Approximately 30-45% of patients
      with suspected appendicitis present with atypical clinical and laboratory
      findings. Recently graded compression ultrasound and thin section unenhanced
      helical CT have been used to establish diagnosis for patients with suspected
      acute appendicitis. The purpose of this study was to determine the diagnostic
      accuracy of thin section unenhanced helical CT protocol in adult patients with
      suspected acute appendicitis. CT scans obtained when patients presented with
      right lower quadrant pain and the clinical impression was equivocal for
      appendicitis were evaluated. Of 296 patients referred for CT, 123 patients
      subsequently underwent surgery. Appendicitis had been correctly predicted in 104
      of 108 patients surgically proven to have appendicitis. Unenhanced helical CT in
      the diagnosis of acute appendicitis had a sensitivity of 96%, specificity of 98%,
      positive predictive value of 97% and negative predictive value of 98%. If no
      definite inflammatory changes are detected, on the basis of our experience we
      recommend that the patient be monitored clinically, and that thin section
      unenhanced helical CT is the optimal technique to detect acute appendicitis in
      adult patients.

PMID- 12200240
TI  - Middle cerebral artery Doppler for the prediction of fetal anaemia in cases
      without hydrops: a practical approach.
AB  - The aim of this study was to assess the value of the middle cerebral artery (MCA)
      Doppler time-averaged mean velocity (TAMV) for the prediction of fetal anaemia in
      at-risk cases without ultrasound evidence of hydrops. The study included 35
      pregnant women with non-hydropic fetuses and with known red cell antibodies,
      referred either because of a rapid increase in antibody levels or because of a
      previous history of a severely anaemic fetus or neonate. After full ultrasound
      examination of the fetus, MCA Doppler TAMV was measured and, if severe anaemia
      was suspected, fetal blood sampling by cordocentesis was performed with blood
      ready for intrauterine transfusion if necessary. Of the 35 fetuses, 28 were
      anaemic and 7 had a haemoglobin (Hb) value within the normal range. There was a
      strong negative correlation between the MCA Doppler TAMV and the Hb values
      (correlation coefficient r=-0.65, p<0.0001). The mean MCA Doppler TAMV (z score)
      for fetuses with normal Hb was 1.55+/-1.68, while that for the anaemic fetuses
      was 4.06+/-1.38, (p<0.001). The sensitivity of the increased MCA Doppler TAMV to
      predict fetal anaemia in these cases was 96.4% and the specificity was 71.4%.
      These data confirm that MCA Doppler TAMV is significantly correlated to fetal Hb.
      This non-invasive investigation can be reliable in predicting anaemia in cases in
      which the need to sample fetal blood is not certain, therefore delaying invasive
      testing until treatment is likely to be required.

PMID- 12200241
TI  - Percutaneous lung biopsies: a survey of UK practice based on 5444 biopsies.
AB  - Percutaneous transthoracic lung biopsies are commonly performed for the
      investigation of lung masses. We describe current practice and complication rates
      in the UK. A postal questionnaire was sent to all centres in the British Thoracic
      Society directory. 157 replies (61% response rate) were received, providing data
      on 5444 biopsies. Mean number of biopsies performed per annum was 30.5 per
      centre; 8% of centres did not perform biopsies, 36% performed <25 biopsies per
      annum, 34% <50, 16% <100 and 6% >100. Consultant radiologists perform 91% of
      biopsies. Written consent was obtained at all centres. The operator obtained
      consent at 50% of centres. Written information for patients was provided at 35
      (24%) centres. Biopsies are performed on a day case basis at 103 (71%) centres.
      Prior to biopsy the following were obtained routinely: CT scan (73% of centres),
      platelet count (73%), full clotting screen (70%), lung function (55%).
      Complications included pneumothorax (20.5% of biopsies), pneumothorax requiring
      chest drain (3.1%), haemoptysis (5.3%) and death (0.15%). The timing of post
      procedure chest radiography was variable. Those centres that performed
      predominantly cutting needle biopsies had similar pneumothorax rates to centres
      performing mainly fine needle biopsies (18.9% vs 18.3%). There is great variation
      in practice throughout the UK. Most procedures are performed on a daycase basis.
      Small pneumothoraces are common but infrequently require treatment. National
      guidelines are needed to ensure consistency of standards.

PMID- 12200242
TI  - Prevalence of osteoporotic bone mineral density at the hip in Britain differs
      substantially from the US over 50 years of age: implications for clinical
      densitometry.
AB  - The purpose of this study was to compare hip bone mineral density (BMD) recorded
      in seven population based cohorts in Britain with the third National Health and
      Nutrition Examination Survey (NHANES III) US population-based reference data, in
      order to assess geographic variation in the prevalence of osteoporosis. Men and
      women aged 50-80+ years were randomly recruited from population and health
      registers. Dual X-ray absorptiometry (DXA) equipment was used to measure BMD at
      the hip, with the femoral neck and the trochanter regions studied. Prevalences of
      osteopenia and osteoporosis were estimated in accordance with World Health
      Organisation diagnostic criteria for women. Young normal data, used to establish
      cut-off criteria, was from NHANES III. Both male and female British subjects over
      50-years-old were found to have significantly higher mean BMD at the femoral neck
      and trochanter than their US counterparts. Decline in BMD with age in British men
      appeared slower than in US men. Between British centres there were also
      statistically significant differences in BMD values in both sexes. British age
      adjusted prevalences of osteopenia in women averaged 20% less than those of
      NHANES III, whereas the prevalence of osteoporosis was substantially lower in
      British subjects of both sexes (55% in women, 68% in men). Thus, applying the US
      NHANES III data as the referent, osteoporosis of the proximal femur in Britain
      appears to be less common than in the US, due primarily to differences in the
      lower tails of the BMD distributions. Providing that the relationship between
      fracture rates and BMD is the same in Britain and the US, it would still be
      appropriate to apply the reference data in fracture risk assessment in the UK.

PMID- 12200243
TI  - Longitudinal changes in mandibular bone mineral density compared with hip bone
      mineral density and quantitative ultrasound at calcaneus and hand phalanges.
AB  - The aim of this prospective study was to evaluate changes in bone mineral density
      (BMD) of the mandible (m-BMD) compared with hip BMD and ultrasound parameters of
      the calcaneus and hand phalanges over 28 months. The study group consisted of 18
      post-menopausal edentulous women with no reasons known to affect bone metabolism,
      such as disease or medication. Each woman had undergone natural menopause. No
      previous fractures were noted. Measurements were performed at baseline and
      repeated after 28 months. Bone status was assessed by measuring BMD using dual
      energy X-ray absorptiometry (DXA) at the mandible and hip and by measuring speed
      of sound (SOS), broadband ultrasound attenuation (BUA), stiffness index (SI) and
      amplitude-dependent SOS (Ad-SOS) using quantitative ultrasound at the calcaneus
      and phalanges of the hand. The coefficient of variation for mandibular
      measurements was 2.06%. BMD of the mandible, femoral neck and Ward's triangle
      decreased significantly (-7.54%, -1.2%, -1.97% per year, respectively, p<0.05),
      whilst BUA, SI and Ad-SOS decreased, but not significantly (-1.1%, -0.47%, -0.08%
      per year, respectively). Both SOS and BMD of the trochanter had almost the same
      value without significant differences. The least significant change (LSC),
      denoting the minimum difference between two successive results in an individual
      that can be considered to reflect a real change, was calculated. With the
      exception of changes in m-BMD, no significant changes were observed at any of the
      sites for the majority of the women (39-89%). 67% of women had a decrease in m
      BMD greater than the LSC and 22% had an increase in m-BMD greater than the LSC.
      Apart from the mandible, other sites showing a large percentage of women with a
      decrease in BMD greater than the LSC were the Ward's triangle (39%) and the
      femoral neck (28%). In conclusion, a 28-month longitudinal study of post
      menopausal women revealed mandibular bone loss assessed by DXA to be much higher
      than in other skeletal sites.

PMID- 12200244
TI  - Does cardiologist- or radiographer-operated fluoroscopy and image acquisition
      influence optimization of patient radiation exposure during routine coronary
      angiography?
AB  - The operator of radiation exposure during coronary angiography varies between
      different centres. The purpose of this study was to explore whether radiation
      dose was lower during cardiologist- or radiographer-controlled radiation exposure
      and to determine if the grade of cardiologist performing angiography influenced
      radiation dose. Patients were randomly allocated either to cardiologist- or
      radiographer-controlled radiation exposure during coronary angiography. Screening
      time and radiation dose during fluoroscopy and image acquisition, measured by
      dose-area product meter, were recorded. Mean radiation dose during cardiologist
      controlled radiation exposure (n=176) of 15.6 Gy cm(2) (95% confidence interval
      (CI), 14.4-16.8) was significantly lower than that produced by the radiographer
      controlled group (n=192) of 17.3 Gy cm(2) (95% CI, 16.2-18.6) (p<0.044). There
      was no significant difference in screening times produced by the two groups of
      radiation exposure operators. The difference in radiation dose produced by the
      two operator groups was principally owing to exposure produced at image
      acquisition. Irrespective of radiation exposure operator, consultant
      cardiologists produced significantly lower screening times and radiation doses
      compared with registrars. During routine coronary angiography, radiographer
      controlled radiation exposure does not reduce screening time or radiation dose.
      Senior cardiologists produce the lowest radiation doses during coronary
      angiography when they are responsible for radiation exposure.

PMID- 12200245
TI  - A pragmatic approach to dosimetric audit in radiotherapy.
AB  - In 1993 a dosimetric audit programme was initiated by physicists from a group of
      hospitals in the South West UK with the aim of detecting dosimetric errors
      greater than 5%. The scope of this programme was developed to cover megavoltage
      and kilovoltage photons as well as electrons. Procedures operated within each
      department were also audited in situations where they could influence dosimetry.
      No dose discrepancies greater than 5% were detected in the course of the audits,
      though differences did correlate with complexity in some situations. These
      measurements provide an ongoing assurance that dosimetry within the participating
      centres is well controlled and provides a firm foundation for clinical practice.

PMID- 12200246
TI  - An alignment method for mammographic X-ray spectroscopy under clinical
      conditions.
AB  - This paper describes an alignment method for mammographic X-ray spectroscopy
      under clinical conditions. A pinhole, a fluorescent screen, a laser device and
      the case for a detector are used for alignment of the focal spot, a collimator
      and a detector. The method determines the line between the focal spot and the
      point of interest in an X-ray field radiographically. The method allows alignment
      for both central axis and off-axis directions.

PMID- 12200248
TI  - Primary osteosarcoma of the uterus with peritoneal osteosarcomatosis: CT
      features.
AB  - A 67-year-old woman presented with lower abdominal pain for 1 month. Pelvic
      ultrasound revealed a calcified uterine mass and ascites. CT showed a heavily
      calcified uterine tumour, with ascites and disseminated calcified nodules in the
      peritoneum. Microscopic and immunohistochemical studies demonstrated features
      typical of osteosarcoma without any epithelial differentiation. Although rare,
      uterine osteosarcoma with associated peritoneal osteosarcomatosis should be
      included in the differential diagnosis of an elderly woman with a calcified
      uterine mass and disseminated peritoneal calcifications.

PMID- 12200247
TI  - Lymphangiolipoma of the lower extremity: 5-year radiological follow-up after
      radiotherapy treatment.
AB  - This report describes a lymphangiolipoma located in the extremity in a young
      woman. Radiotherapy effectively controlled recurrent lymphangiolipoma of the left
      upper leg that had been judged inoperable by limb-sparing surgical resection. In
      the case presented here, a dose of 50 Gy in 25 fractions over 5 weeks was
      employed without long-term complications after 5-year follow-up.

PMID- 12200249
TI  - Appendicitis: spectrum of appearances on helical CT.
AB  - Acute appendicitis has extremely varied clinical presentations. A delayed or
      missed diagnosis may result in severe adverse consequences. Helical CT is
      evolving as an important diagnostic aid, but the CT signs can be varied and can
      easily be overlooked by the unwary. This pictorial review illustrates the
      spectrum of radiological signs and appearances of appendicitis on helical CT.

PMID- 12200250
TI  - Abdominal pain and vomiting after gynaecological surgery.

PMID- 12200251
TI  - Blade motion and nutrient flux to the kelp, Eisenia arborea.
AB  - Marine algae rely on currents and waves to replenish the nutrients required for
      photosynthesis. The interaction of algal blades with flow often involves dynamic
      reorientations of the blade surface (pitching and flapping) that may in turn
      affect nutrient flux. As a first step toward understanding the consequences of
      blade motion, we explore the effect of oscillatory pitching on the flux to a flat
      plate and to two morphologies of the kelp Eisenia arborea. In slow flow
      (equivalent to a water velocity of 2.7 cm s(-1)), pitching increases the time
      averaged flux to both kelp morphologies, but not to the plate. In fast flow
      (equivalent to 20 cm s(-1) in water), pitching has negligible effect on flux
      regardless of shape. For many aspects of flux, the flat plate is a reliable model
      for the flow-protected algal blade, but predictions made from the plate would
      substantially underestimate the flux to the flow-exposed blade. These
      measurements highlight the complexities of flow-related nutrient transport and
      the need to understand better the dynamic interactions among nutrient flux, blade
      motion, blade morphology, and water flow.

PMID- 12200252
TI  - Ontogeny of squid mantle function: changes in the mechanics of escape-jet
      locomotion in the oval squid, Sepioteuthis lessoniana lesson, 1830.
AB  - In Sepioteuthis lessoniana, the oval squid, ontogenetic changes in the kinematics
      of the mantle during escape-jet locomotion imply a decline in the relative mass
      flux of the escape jet and may affect the peak weight-specific thrust of the
      escape jet. To examine the relationship between ontogenetic changes in the
      kinematics of the mantle and the thrust generated during the escape jet, we
      simultaneously measured the peak thrust and the kinematics of the mantle of squid
      tethered to a force transducer. We tested an ontogenetic series of S. lessoniana
      that ranged in size from 5 to 40 mm dorsal mantle length (DML). In newly hatched
      squids, thrust peaked 40 ms after the start of the escape jet and reached a
      maximum of between 0.10 mN and 0.80 mN. In the largest animals, thrust peaked 70
      ms after the start of the escape jet and reached a maximum of between 18 mN and
      110 mN. Peak thrust was normalized by the wet weight of the squid and also by the
      cross-sectional area of the circumferential muscle that provides power for the
      escape jet. The weight-specific peak thrust of the escape jet averaged 0.36 in
      newly hatched squid and increased significantly to an average of 1.5 in the
      largest squids measured (P < 0.01). The thrust per unit area of circumferential
      muscle averaged 0.25 mN/mm(2) in hatchlings and increased significantly to an
      average of 1.4 mN/mm(2) in the largest animals tested (P < 0.01). The impulse of
      the escape jet was also lowest in newly hatched individuals (1.3 mN. s) and
      increased significantly to 1000 mN. s in the largest squids measured (P < 0.01).
      These ontogenetic changes in the mechanics of the escape jet suggest (1) that
      propulsion efficiency of the exhalant phase of the jet is highest in hatchlings,
      and (2) that the mechanics of the circumferential muscles of the mantle change
      during growth.

PMID- 12200253
TI  - Anatomical correlates of venom production in Conus californicus.
AB  - Like all members of the genus, Conus californicus has a specialized venom
      apparatus, including a modified radular tooth, with which it injects paralyzing
      venom into its prey. In this paper the venom duct and its connection to the
      pharynx, along with the radular sac and teeth, were examined using light and
      transmission electron microscopy. The general anatomy of the venom apparatus
      resembles that in other members of the genus, but several features are described
      that have not been previously reported for other species. The proximal
      (posterior) quarter of the venom duct is composed of a complex epithelium that
      may be specialized for active transport rather than secretion. The distal portion
      of the duct is composed of a different type of epithelium, suggestive of
      holocrine secretion, and the cells display prominent intracellular granules of at
      least two types. Similar granules fill the lumen of the duct. The passageway
      between the lumen of the venom duct and pharynx is a flattened branching channel
      that narrows to a width of 10 micro m and is lined by a unique cell type of
      unknown function. Granular material similar to that in the venom duct was also
      found in the lumen of individual teeth within the radular sac. Mass spectrometry
      (MALDI-TOF) demonstrated the presence of putative peptides in material derived
      from the tooth lumen, and all of the more prominent species were also evident in
      the anterior venom duct. Radular teeth thus appear to be loaded with peptide
      toxins while they are still in the radular sac.

PMID- 12200255
TI  - Helical nature of sperm swimming affects the fit of fertilization-kinetics models
      to empirical data.
AB  - Models of fertilization kinetics rely upon estimates of the swimming velocity of
      sperm to predict collision rates between egg and sperm. Most investigators
      measure sperm swimming velocity without accounting for the helical motion of
      sperm, thereby obtaining an inflated estimate of the velocity with which sperm
      approach eggs. In turn, models of fertilization predict inflated rates of
      sperm/egg collision. I observed sea urchin sperm colliding with eggs, quantified
      the rate of sperm/egg collision, and measured sperm velocity as a component of
      the helix through which they swim. I also adjusted the "target size" of eggs to
      reflect the diameter of the helix. My estimate of sperm swimming velocity is an
      order of magnitude lower than other estimates for the same species. By using
      helical parameters in fertilization kinetics models and accounting for dead sperm
      in laboratory trials, I was able to accurately predict lower rates of sperm/egg
      collision. Moreover, making these adjustments in the model increased the
      estimated proportion of sperm that initiate fertilization by 6- to 7-fold,
      suggesting that a better understanding of sperm swimming might lead to a more
      complete understanding of fertilization biology and natural selection on gamete
      traits.

PMID- 12200254
TI  - Respiratory and acid-base physiology of the purple sea urchin, Strongylocentrotus
      purpuratus, during air exposure: presence and function of a facultative lung.
AB  - Upon exposure to air (emersion), the purple sea urchin Strongylocentrotus
      purpuratus releases an "emersion fluid" from its esophagus. Release of this fluid
      causes air to appear within the test (or calcareous theca), most likely inside
      the intestine. The air space is large, occupying 33.5% of the volume of the
      intrathecal space. The intestine containing air forms a facultative lung and
      contributes to the oxygenation of the perivisceral coelomic fluid (PCF) during
      emersion. During emersion, the mean partial pressure of oxygen (PO(2)) of the PCF
      declined from 56 to 24 torr (1 torr = 0.1333 kPa) after 2 h, remained relatively
      unchanged after 4 h, and rose to 39 torr after 8 h. The partial pressure of
      carbon dioxide (PCO(2)) rose from 2.6 to 3.8 torr after 2 h, remained unchanged
      after 4 h, and declined to 2.7 after 8 h. Due to the elevation of PCO(2) PCF pH
      declined from 7.41 to 7.17. PCF osmotic concentration, calcium ion concentration,
      chloride ion concentration, ammonium ion concentration, and protein concentration
      were unchanged by air exposure. Lactate levels in the PCF were undetectable. S.
      purpuratus was an osmoconformer and a chloride ion conformer at salinities down
      to 20.9 ppt. Below this salinity, the sea urchins died. The respiratory acidosis
      resulting from air exposure was uncompensated, supporting the hypothesis that
      compensation for a respiratory acidosis induced by air exposure does not occur in
      organisms that are unable to regulate ions in a dilute environment. We suggest
      that the facultative lung ensures a minimal PO(2) in the PCF, which may be
      especially important when the intrathecal space is full of ripe gonads, allowing
      the gonads to be more reliant on aerobic metabolism.

PMID- 12200256
TI  - Evolution of fast development of planktonic embryos to early swimming.
AB  - Planktonic embryos of marine animals swim at an early stage and age. Although
      natural selection has apparently favored rapid development of structures for
      swimming, taxa have not converged on the same, minimal time from first cell
      division to first swimming. Comparisons of 34 species with planktonic embryos in
      10 phyla revealed factors that account for variation in time to swimming. Time to
      first swimming correlated significantly with time from first to second cleavage
      (first cell cycle) in analyses of all embryos sampled and separately within the
      Spiralia and Echinodermata. Time to first swimming also correlated significantly
      with egg diameter in some clades, but not in all. Correlations between egg
      diameter and cell cycle duration were low except for the three species of
      Urochordata. Development to a feeding or nonfeeding larva did not affect time to
      first swimming beyond effects attributable to egg size. Time to first swimming
      did not correlate with type of locomotion developed (uniciliated cells,
      multiciliated cells, or muscle). Nonetheless, differences in locomotion are
      associated with changes in cell cycle durations prior to swimming. The ratios of
      time to first swimming and time for first cell cycle suggests that allocation of
      time to multiplication of cells versus differentiation of cells is resolved
      differently in species with different types of locomotion.

PMID- 12200257
TI  - Immunocytochemically defined populations of neurons progressively increase in
      size through embryogenesis of Hydra vulgaris.
AB  - The hydra nervous system shares many features with nervous systems of more
      complex organisms but serves as a unique model system due to its simplicity and
      constant regeneration. Development of neuron populations during and after hydra
      embryogenesis is not well understood. In this study, neurons were identified at
      prehatching and posthatching stages with RFamide or JD1 antisera. These
      populations were further subdivided into ganglion, sensory, or unclassifiable
      neurons, and all identified populations were statistically analyzed over
      developmental time. RFamide-positive neurons appeared 20 days after the cuticle
      formed around the embryo. The JD1-positive neuron population appeared just after
      hatching, but by adulthood it had surpassed the size of the RFamide-positive
      population. All neuron populations progressively increased through their adult
      levels. Density of most of the populations, however, did not. For instance,
      during the 5-fold increase in size that the hydra experienced between 5 days
      posthatching and adulthood, the number of RFamide-positive neurons rose
      approximately 2-fold and the number of JD1-positive neurons 4-fold. However, the
      density of neurons in each of these populations fell. These data do not support
      the hypothesis that large-scale culling of neurons during development, frequently
      found in other animals, occurs in hydra.

PMID- 12200258
TI  - Embryonic velar structure and function of two sibling species of Crepidula with
      different modes of development.
AB  - The structure and function of the embryonic velum of two closely related species
      of Crepidula with different modes of development are examined. The velum of C.
      dilatata, a direct developer whose embryos feed on nurse eggs, does not differ
      substantially from the velum of C. fecunda, a species with planktotrophic larvae.
      Although velar ciliation develops earlier in embryos of C. dilatata, embryos of
      both species were able to feed on small particles, using the opposed-band ciliary
      mechanism. However, the embryos of C. dilatata lose this ability as they grow.
      The embryos of C. dilatata were not able to swim, whereas those of C. fecunda
      swam consistently in vials of seawater. This difference in swimming ability is
      probably due to differences in velum-body size allometry between the two species.

PMID- 12200259
TI  - Embryogenesis and development of Epimenia babai (Mollusca Neomeniomorpha).
AB  - Neomenioid aplacophorans (= Solenogastres) constitute one of the main lineages of
      molluscs. Developmental data of early embryogenesis and larval development of
      neomenioids are available for some species based on histological sections. I used
      other techniques to study the development of Epimenia babai Salvini-Plawen, 1997,
      and here I report new data on neomenioid development. The embryos of E. babai are
      lecithotrophic and cleavage is spiral, unequal, and holoblastic. Two polar lobes
      are formed, one at the first cleavage stage and one at the second cleavage stage.
      No evidence of external metameric iteration is visible through scanning electron
      microscopy or histology at any stage. A ciliated foot, a pedal pit, and
      aragonitic spicules develop from the definitive ectoderm. A spicule begins as a
      solid tip, continues to an open-ended hollow spicule, and finally becomes a
      closed-ended hollow spicule. The free-swimming trochophore larvae of E. babai
      have been considered unusual in lacking the characteristic neomenioid cellular
      test, an outer locomotory structure within which the entire definitive adult body
      develops. However, through the use of scanning electron and light microscopy,
      semithin sections, Hoechst nuclear staining, and programmed cell death staining
      to study the ontogeny and fate of the apical cells, I show that the entire pre
      oral sphere (the apical cap) of the larvae is similar to the test of the other
      neomenioids. The results suggest that the test of the neomenioid larvae is an
      enlarged pre-oral sphere of a trochophore. The test morphologies of neomenioid
      larvae are compared to those of pericalymma larvae of protobranch bivalves, and
      the homology and evolution of molluscan larval tests is discussed.

PMID- 12200260
TI  - Undifferentiated cells in the snail myocardium are capable of DNA synthesis and
      myodifferentiation.
AB  - Cellular mechanisms of heart-muscle growth in the snail Achatina fulica have been
      studied using cytophotometry and electron microscopic autoradiography.
      Cytophotometric DNA measurements showed that the snail cardiomyocytes are
      mononucleated cells with diploid nuclei. Ultrastructural analysis of the snail
      myocardium revealed that, in addition to mature myocytes, it contains small
      roundish undifferentiated cells (UCs) and poorly differentiated muscle cells. EM
      autoradiography detected silver grains over the nuclei of UCs 2 h after injection
      of tritiated thymidine ([(3)H]Tdr), while the nuclei of both mature and poorly
      differentiated myocytes remained unlabeled. In EM autographs of the myocardial
      tissue fixed 14 days after [(3)H]Tdr administration, labeled myonuclei were
      evident, which may suggest some myodifferentiation of prelabeled UCs. Many
      labeled UCs persist for 14 days after a single [(3)H]Tdr injection, suggesting
      that not all UCs undergo myodifferentiation after passing through the cell cycle,
      and that those that do not can enter the next cycle. UCs in the snail myocardium
      presumably provide not only reserve but also stem cells for myocytes. Thus, the
      heart muscle of the adult snail consists of mononucleated diploid myocytes with
      blocked proliferative activity and a renewable population of precursor myogenic
      cells. The results obtained suggest that the growth of this muscle involves a
      myoblastic mechanism of myogenesis; this mechanism differs from that of
      vertebrate cardiac muscle growth, which is non-myoblastic-that is, based on
      proliferation or polyploidization of cardiomyocytes. Evolutionary aspects of
      cellular mechanisms of the heart-muscle growth are discussed.

PMID- 12200261
TI  - Predator-induced behavioral and morphological plasticity in the tropical marine
      Gastropod Strombus gigas.
AB  - Florida queen conch stocks once supported a significant fishery, but overfishing
      prompted the state of Florida to institute a harvest moratorium in 1985. Despite
      the closure of the fishery, the queen conch population has been slow to recover.
      One method used in the efforts to restore the Florida conch population has been
      to release hatchery-reared juvenile conch into the wild; however, suboptimal
      predator avoidance responses and lighter shell weights relative to their wild
      counterparts have been implicated in the high mortality rates of released
      hatchery juveniles. We conducted a series of experiments in which hatchery-reared
      juvenile conch were exposed to a predator, the spiny lobster (Panulirus argus),
      to determine whether they could develop behavioral and morphological
      characteristics that would improve survival. Experiments were conducted in tanks
      with a calcareous sand substrate to simulate a natural environment. Conditioned
      conch were exposed to caged lobsters while conch in the control tanks were
      exposed to empty cages. Conditioned conch moved significantly less and buried
      themselves more frequently than the naive control conch. Morphometric data
      indicated that the conditioned conch grew at a significantly slower rate than the
      naive conch, but the shell weights of the two groups were not significantly
      different. This implies that the conditioned conch had thicker or denser shells
      than the control group. As a result, the conditioned conch had significantly
      higher survival than naive conch in a subsequent predation experiment in which a
      lobster was allowed to roam free in each tank for 24 hours. In the future, the
      conditioning protocols documented in this study will be used to increase the
      survival of hatchery-reared conch in the wild.

PMID- 12200262
TI  - Biodegradation of the polyketide toxin cercosporin.
AB  - Cercosporin is a non-host-specific polyketide toxin produced by many species of
      plant pathogens belonging to the genus Cercospora. This red-pigmented, light
      activated toxin is an important pathogenicity determinant for Cercospora species.
      In this study, we screened 244 bacterial isolates representing 12 different
      genera for the ability to degrade cercosporin. Cercosporin degradation was
      determined by screening for the presence of cleared zones surrounding colonies on
      cercosporin-containing culture medium and was confirmed by assaying the kinetics
      of degradation in liquid medium. Bacteria belonging to four different genera
      exhibited the cercosporin-degrading phenotype. The isolates with the greatest
      cercosporin-degrading activity belonged to Xanthomonas campestris pv. zinniae and
      X. campestris pv. pruni. Isolates of these pathovars removed over 90% of the
      cercosporin from culture medium within 48 h. Bacterial degradation of red
      cercosporin was accompanied by a shift in the color of the growth medium to brown
      and then green. The disappearance of cercosporin was accompanied by the
      appearance of a transient green product, designated xanosporic acid. Xanosporic
      acid and its more stable lactone derivative, xanosporolactone, are nontoxic to
      cercosporin-sensitive fungi and to plant tissue and are labile in the presence of
      light. Detailed spectroscopic analysis (to be reported in a separate publication)
      of xanosporolactone revealed that cercosporin loses one methoxyl group and gains
      one oxygen atom in the bacterial conversion. The resulting chromophore (4,9
      dihydroxy-3-oxaperlylen-10H-10-one) has never been reported before but is
      biosynthetically plausible via oxygen insertion by a cytochrome P-450 enzyme.

PMID- 12200263
TI  - Correspondence of high levels of beta-exotoxin I and the presence of cry1B in
      Bacillus thuringiensis.
AB  - Examination of 640 natural isolates of Bacillus thuringiensis showed that the 58
      strains (9%) whose supernatants were toxic to Anthonomus grandis (Coleoptera:
      Curculionidae) produced between 10 and 175 micro g of beta-exotoxin I per ml. We
      also found that 55 (46%) of a sample of 118 strains whose culture supernatants
      were not toxic to A. grandis nevertheless produced between 2 and 5 micro g/ml.
      However, these amounts of beta-exotoxin I were below the threshold for detectable
      toxicity against this insect species. Secretion of large amounts of beta-exotoxin
      I was strongly associated with the presence of cry1B and vip2 genes in the 640
      natural B. thuringiensis isolates studied. We concluded that strains carrying
      cry1B and vip2 genes also possess, on the same plasmid, genetic determinants
      necessary to promote high levels of production of beta-exotoxin I.

PMID- 12200264
TI  - Tissue localization of the endosymbiotic bacterium "Candidatus Blochmannia
      floridanus" in adults and larvae of the carpenter ant Camponotus floridanus.
AB  - The distribution of endosymbiotic bacteria in different tissues of queens, males,
      and workers of the carpenter ant Camponotus floridanus was investigated by light
      and electron microscopy and by in situ hybridization. A large number of bacteria
      could be detected in bacteriocytes within the midguts of workers, young virgin
      queens, and males. Large amounts of bacteria were also found in the oocytes of
      workers and queens. In contrast, bacteria were not present in oocyte-associated
      cells or in the spermathecae of mature queens, although occasionally a small
      number of bacteria could be detected in the testis follicles of males.
      Interestingly, the number of bacteriocytes in mature queens was strongly reduced
      and the bacteriocytes contained only very few or no bacteria at all, although the
      endosymbionts were present in huge amounts in the ovaries of the same animals.
      During embryogenesis of the deposited egg, the bacteria were concentrated in a
      ring of endodermal tissue destined to become the midgut in later developmental
      stages. However, during larval development, bacteria could also be detected in
      other tissues although to a lesser extent. Only in the last-instar larvae were
      bacteria found exclusively in the midgut tissue within typical bacteriocytes.
      Tetracycline and rifampin efficiently cleansed C. floridanus workers of their
      symbionts and the bacteriocytes of these animals still remained empty several
      months after treatment had ceased. Despite the lack of their endosymbionts, these
      adult animals were able to survive without any obvious negative effect under
      normal cultivation conditions.

PMID- 12200265
TI  - Development of a standard test to assess the resistance of Staphylococcus aureus
      biofilm cells to disinfectants.
AB  - A standardized disinfectant test for Staphylococcus aureus cells in biofilms was
      developed. Two disinfectants, the membrane-active compound benzalkonium chloride
      (BAC) and the oxidizing agent sodium hypochlorite, were used to evaluate the
      biofilm test. S. aureus formed biofilms on glass, stainless steel, and
      polystyrene in a simple system with constant nutrient flow that mimicked as
      closely as possible the conditions used in the current standard European
      disinfectant test (EN 1040). The biofilm that was formed on glass contained cell
      clumps and extracellular polysaccharides. The average surface coverage was 60%,
      and most (92%) of the biofilm cells were viable. Biofilm formation and biofilm
      disinfection in different experiments were reproducible. For biofilms exposed to
      BAC and hypochlorite the concentrations needed to achieve 4-log killing were 50
      and 600 times higher, respectively, than the concentrations needed to achieve
      this level of killing with the European phase 1 suspension test cells. Our
      results show that a standardized disinfectant test for biofilm cells is a useful
      addition to the current standard tests.

PMID- 12200266
TI  - Effect of a Sinorhizobium meliloti strain with a modified putA gene on the
      rhizosphere microbial community of alfalfa.
AB  - The success of a rhizobial inoculant in the soil depends to a large extent on its
      capacity to compete against indigenous strains. M403, a Sinorhizobium meliloti
      strain with enhanced competitiveness for nodule occupancy, was recently
      constructed by introducing a plasmid containing an extra copy of a modified putA
      (proline dehydrogenase) gene. This strain and M401, a control strain carrying the
      same plasmid without the modified gene, were used as soil inoculants for alfalfa
      in a contained field release experiment at Leon, Spain. In this study, we
      determined the effects of these two strains on the indigenous microbial
      community. 16S rRNA genes were obtained from the rhizosphere of alfalfa
      inoculated with strain M403 or strain M401 or from noninoculated plants by
      amplification of DNA from soil with bacterial group-specific primers. These genes
      were analyzed and compared by restriction fragment length polymorphism and
      temperature gradient gel electrophoresis. The results allowed us to differentiate
      between alterations in the microbial community apparently caused by inoculation
      and by the rhizosphere effect and seasonal fluctuations induced by the alfalfa
      plants and by the environment. Only moderate inoculation-dependent effects could
      be detected, while the alfalfa plants appeared to have a much stronger influence
      on the microbial community.

PMID- 12200267
TI  - Environmental regulation of Campylobacter jejuni major outer membrane protein
      porin expression in Escherichia coli monitored by using green fluorescent
      protein.
AB  - Porins allow exchanges between bacteria and their environment. In the gram
      negative food-borne pathogen Campylobacter jejuni two porins, major outer
      membrane protein (MOMP) and Omp50, have been identified. MOMP is synthesized at a
      very high level under laboratory culture conditions, suggesting that its promoter
      functions very efficiently under these conditions. In Campylobacter samples, we
      observed that MOMP porin expression increased at a high temperature (42 degrees
      C) or a high pH (pH 8.5) compared to expression at a low temperature (31 degrees
      C) or an acidic pH (pH 5.5). To study the regulation of MOMP expression at the
      transcriptional level, we constructed an momp-gfp fusion in which gfp expression
      was put under the control of the momp promoter. Interestingly, we observed the
      same pattern of regulation in Escherichia coli, as monitored by green fluorescent
      protein production, that was found in CAMPYLOBACTER: The ranges of pH and
      temperature tested are physiologically relevant, because they can be found in the
      digestive tracts of both birds and humans, which are both colonized by
      CAMPYLOBACTER: Our results suggest that a component of the regulatory mechanism
      is conserved in C. jejuni and E. coli. However, medium osmolarity and sodium
      salicylate did not have a significant effect on C. jejuni momp promoter activity
      in E. coli, suggesting that major regulatory elements of E. coli porin expression
      do not participate in MOMP regulation. In contrast, mechanisms involving DNA
      supercoiling may be involved, as shown by DNA gyrase inhibition assays. These
      findings are a step towards determining the role of outer membrane proteins in
      the adaptation of C. jejuni to its environment.

PMID- 12200268
TI  - Genetic heterogeneity in Bacillus sporothermodurans as demonstrated by ribotyping
      and repetitive extragenic palindromic-PCR fingerprinting.
AB  - Thirty-eight strains of Bacillus sporothermodurans isolated from ultra-high
      temperature (UHT)-treated milk or sterilized milk (UHT isolates) and from animal
      feed or raw milk (farm isolates) were characterized by automated ribotyping and
      by repetitive extragenic palindromic (REP)-PCR fingerprinting. By investigating
      the genetic relationships among isolates from these various sources, the relative
      importance of different contamination sources could be evaluated. The results of
      the separate clustering analyses of the PvuII and EcoRI ribopatterns and the REP
      PCR patterns were largely consistent with each other and revealed the existence
      of two main clusters; there was one homogeneous group containing all (REP-PCR) or
      most (ribotyping) of the UHT isolates, and there was a second more diverse group
      comprising the farm isolates. A combined three-dimensional analysis of all data
      showed that three German UHT isolates did not belong to the compact group
      containing the majority of the UHT isolates. These results demonstrate that B.
      sporothermodurans is more heterogeneous than previously assumed and that most of
      the UHT isolates form a genetically distinct subgroup and are capable of
      producing highly heat-resistant spores. The close genetic relationship of these
      UHT isolates suggests a clonal origin of a few predominant strains of B.
      sporothermodurans that can be found in UHT-treated or sterilized milk products.

PMID- 12200269
TI  - Quantification of uncultured Ruminococcus obeum-like bacteria in human fecal
      samples by fluorescent in situ hybridization and flow cytometry using 16S rRNA
      targeted probes.
AB  - A 16S rRNA-targeted probe was designed and validated in order to quantify the
      number of uncultured Ruminococcus obeum-like bacteria by fluorescent in situ
      hybridization (FISH). These bacteria have frequently been found in 16S ribosomal
      DNA clone libraries prepared from bacterial communities in the human intestine.
      Thirty-two reference strains from the human intestine, including a
      phylogenetically related strain and strains of some other Ruminococcus species,
      were used as negative controls and did not hybridize with the new probe.
      Microscopic and flow cytometric analyses revealed that a group of morphologically
      similar bacteria in feces did hybridize with this probe. Moreover, it was found
      that all hybridizing cells also hybridized with a probe specific for the
      Clostridium coccoides-Eubacterium rectale group, a group that includes the
      uncultured R. obeum-like bacteria. Quantification of the uncultured R. obeum-like
      bacteria and the C. coccoides-E. rectale group by flow cytometry and microscopy
      revealed that these groups comprised approximately 2.5 and 16% of the total
      community in fecal samples, respectively. The uncultured R. obeum-like bacteria
      comprise about 16% of the C. coccoides-E. rectale group. These results indicate
      that the uncultured R. obeum-like bacteria are numerically important in human
      feces. Statistical analysis revealed no significant difference between the
      microscopic and flow cytometric counts and the different feces sampling times,
      while a significant host-specific effect on the counts was observed. Our data
      demonstrate that the combination of FISH and flow cytometry is a useful approach
      for studying the ecology of uncultured bacteria in the human gastrointestinal
      tract.

PMID- 12200270
TI  - Cyclization reaction catalyzed by glycogen debranching enzyme (EC 2.4.1.25/EC
      3.2.1.33) and its potential for cycloamylose production.
AB  - Glycogen debranching enzyme (GDE) has 4-alpha-glucanotransferase and amylo-1,6
      glucosidase activities in the single polypeptide chain. We analyzed the detailed
      action profile of GDE from Saccharomyces cerevisiae on amylose and tested whether
      GDE catalyzes cyclization of amylose. GDE treatment resulted in a rapid reduction
      of absorbance of iodine-amylose complex and the accumulation of a product that
      was resistant to an exo-amylase (glucoamylase [GA]) but was degraded by an endo
      type alpha-amylase to glucose and maltose. These results indicated that GDE
      catalyzed cyclization of amylose to produce cyclic alpha-1,4 glucan
      (cycloamylose). The formation of cycloamylose was confirmed by high-performance
      anion-exchange chromatography, and the size was shown to range from a degree of
      polymerization of 11 to a degree of polymerization around 50. The minimum size
      and the size distribution of cycloamylose were different from those of
      cycloamylose produced by other 4-alpha-glucanotransferases. GDE also efficiently
      produced cycloamylose even from the branched glucan substrate, starch,
      demonstrating its potential for industrial production of cycloamylose.

PMID- 12200271
TI  - A stationary-phase acyl-coenzyme A synthetase of Streptomyces coelicolor A3(2) is
      necessary for the normal onset of antibiotic production.
AB  - The fadD1 and macs1 genes of Streptomyces coelicolor are part of a two-gene
      operon. Both genes encode putative acyl coenzyme A synthetases (ACSs). The amino
      acid sequence of FadD1 has high homology with those of several ACSs, while MACS1
      has the closest homology with medium-chain ACSs, broadly known as SA proteins.
      Like FadD of Escherichia coli, FadD1 also has a broad substrate specificity,
      although saturated long-chain fatty acids appears to be the preferred substrate.
      fadD1 is a growth-phase-regulated gene, and its mRNA is detected only during the
      stationary phase of growth. Interestingly, a mutation in fadD1 alters the levels
      of another ACS or ACSs, both at the stationary phase and at the exponential phase
      of growth, at least when glucose is used as a main carbon source. The mutant also
      shows a severe deficiency in antibiotic production, and at least for Act
      biosynthesis, this deficiency seems to be related to delayed expression of the
      Act biosynthetic genes. Antibiotic production is restored by the introduction of
      a wt fadD1 allele into the cell, demonstrating a strict link between ACS activity
      and the biosynthesis of secondary metabolites. The results of this study indicate
      that the ACSs may be useful targets for the design of rational approaches to
      improving antibiotic production.

PMID- 12200272
TI  - Biochemical evidence for formate transfer in syntrophic propionate-oxidizing
      cocultures of Syntrophobacter fumaroxidans and Methanospirillum hungatei.
AB  - The hydrogenase and formate dehydrogenase levels in Syntrophobacter fumaroxidans
      and Methanospirillum hungatei were studied in syntrophic propionate-oxidizing
      cultures and compared to the levels in axenic cultures of both organisms. Cells
      grown syntrophically were separated from each other by Percoll gradient
      centrifugation. In S. fumaroxidans both formate dehydrogenase and hydrogenase
      levels were highest in cells which were grown syntrophically, while the formate
      H(2) lyase activities were comparable under the conditions tested. In M. hungatei
      the formate dehydrogenase and formate-H(2) lyase levels were highest in cells
      grown syntrophically, while the hydrogenase levels in syntrophically grown cells
      were comparable to those in cells grown on formate. Reconstituted syntrophic
      cultures from axenic cultures immediately resumed syntrophic growth, and the
      calculated growth rates of these cultures were highest for cells which were
      inoculated from the axenic S. fumaroxidans cultures that exhibited the highest
      formate dehydrogenase activities. The results suggest that formate is the
      preferred electron carrier in syntrophic propionate-oxidizing cocultures of S.
      fumaroxidans and M. hungatei.

PMID- 12200273
TI  - Purification and immunogenicity of a recombinant Bordetella pertussis S1S3FHA
      fusion protein expressed by Streptococcus gordonii.
AB  - Acellular pertussis vaccines typically consist of antigens isolated from
      Bordetella pertussis, and pertussis toxin (PT) and filamentous hemagglutinin
      (FHA) are two prominent components. One of the disadvantages of a multiple
      component vaccine is the cost associated with the production of the individual
      components. In this study, we constructed an in-frame fusion protein consisting
      of PT fragments (179 amino acids of PT subunit S1 and 180 amino acids of PT
      subunit S3) and a 456-amino-acid type I domain of FHA. The fusion protein was
      expressed by the commensal oral bacterium Streptococcus gordonii. The fusion
      protein was secreted into the culture medium as an expected 155-kDa protein,
      which was recognized by a polyclonal anti-PT antibody, a monoclonal anti-S1
      antibody, and a monoclonal anti-FHA antibody. The fusion protein was purified
      from the culture supernatant by affinity and gel permeation chromatography. The
      immunogenicity of the purified fusion protein was assessed in BALB/c mice by
      performing parenteral and mucosal immunization experiments. When given
      parenterally, the fusion protein elicited a very strong antibody titer against
      the FHA type I domain, a moderate titer against native FHA, and a weak titer
      against PT. When given mucosally, it elicited a systemic response and a mucosal
      response to FHA and PT. In Western blots, the immune sera recognized the S1, S3,
      and S2 subunits of PT. These data collectively indicate that fragments of the
      pertussis vaccine components can be expressed in a single fusion protein by S.
      gordonii and that the fusion protein is immunogenic. This multivalent fusion
      protein approach may be used in designing a new generation of acellular pertussis
      vaccines.

PMID- 12200274
TI  - Hxt-carrier-mediated glucose efflux upon exposure of Saccharomyces cerevisiae to
      excess maltose.
AB  - When wild-type Saccharomyces cerevisiae strains pregrown in maltose-limited
      chemostat cultures were exposed to excess maltose, release of glucose into the
      external medium was observed. Control experiments confirmed that glucose release
      was not caused by cell lysis or extracellular maltose hydrolysis. To test the
      hypothesis that glucose efflux involved plasma membrane glucose transporters,
      experiments were performed with an S. cerevisiae strain in which all members of
      the hexose transporter (HXT) gene family had been eliminated and with an isogenic
      reference strain. Glucose efflux was virtually eliminated in the hexose-transport
      deficient strain. This constitutes experimental proof that Hxt transporters
      facilitate export of glucose from S. cerevisiae cells. After exposure of the
      hexose-transport-deficient strain to excess maltose, an increase in the
      intracellular glucose level was observed, while the concentrations of glucose 6
      phosphate and ATP remained relatively low. These results demonstrate that glucose
      efflux can occur as a result of uncoordinated expression of the initial steps of
      maltose metabolism and the subsequent reactions in glucose dissimilation. This is
      a relevant phenomenon for selection of maltose-constitutive strains for baking
      and brewing.

PMID- 12200275
TI  - Albidovulum inexpectatum gen. nov., sp. nov., a nonphotosynthetic and slightly
      thermophilic bacterium from a marine hot spring that is very closely related to
      members of the photosynthetic genus Rhodovulum.
AB  - Several bacterial isolates, with an optimum growth temperature of about 50
      degrees C, were recovered from the marine hot spring at Ferraria on the island of
      Sao Miguel in the Azores. The geothermal water emerged from a porous lava flow
      and rapidly cooled in contact with seawater except at low tide. The bacterial
      species represented by strains FRR-10(T) and FRR-11 was nonpigmented, strictly
      aerobic, and organotrophic. Several genes, bchZ, pufB, pufA, pufL, or pufM,
      encoding the photosynthetic reaction center proteins and the core light
      harvesting complexes were not detected in these strains. The organism oxidized
      thiosulfate to sulfate with enhancement of growth. The organism did not require
      additional NaCl in the culture medium for growth, but NaCl at 1.0% enhanced
      growth. Phylogenetic analyses using the 16S rRNA gene sequence of strain FRR
      10(T) indicated that the new organism represented a new species of the alpha-3
      subclass of the Proteobacteria and that it branches within the species of the
      genus Rhodovulum. The contradiction of classifying an organism which branches
      within the radiation of the genus Rhodovulum but does not possess the hallmark
      characteristics of this genus is discussed. However, the absence of several of
      these characteristics, namely, the lack of photosynthesis and pigmentation, which
      could be related to colonization of dark environments, and growth at high
      temperatures, leads to our proposal that strains FRR-10(T) and FRR-11 should be
      classified as a new species of a novel genus, Albidovulum inexpectatum,
      representing, at present, the most thermophilic organism within the alpha-3
      subclass of the Proteobacteria.

PMID- 12200276
TI  - Expression of genes encoding F(1)-ATPase results in uncoupling of glycolysis from
      biomass production in Lactococcus lactis.
AB  - We studied how the introduction of an additional ATP-consuming reaction affects
      the metabolic fluxes in Lactococcus lactis. Genes encoding the hydrolytic part of
      the F(1) domain of the membrane-bound (F(1)F(0)) H(+)-ATPase were expressed from
      a range of synthetic constitutive promoters. Expression of the genes encoding
      F(1)-ATPase was found to decrease the intracellular energy level and resulted in
      a decrease in the growth rate. The yield of biomass also decreased, which showed
      that the incorporated F(1)-ATPase activity caused glycolysis to be uncoupled from
      biomass production. The increase in ATPase activity did not shift metabolism from
      homolactic to mixed-acid fermentation, which indicated that a low energy state is
      not the signal for such a change. The effect of uncoupled ATPase activity on the
      glycolytic flux depended on the growth conditions. The uncoupling stimulated the
      glycolytic flux threefold in nongrowing cells resuspended in buffer, but in
      steadily growing cells no increase in flux was observed. The latter result shows
      that glycolysis occurs close to its maximal capacity and indicates that control
      of the glycolytic flux under these conditions resides in the glycolytic reactions
      or in sugar transport.

PMID- 12200277
TI  - Molecular characterization of a novel glucosyltransferase from Lactobacillus
      reuteri strain 121 synthesizing a unique, highly branched glucan with alpha-(1-
      >4) and alpha-(1-->6) glucosidic bonds.
AB  - Lactobacillus reuteri strain 121 produces a unique, highly branched, soluble
      glucan in which the majority of the linkages are of the alpha-(1-->4) glucosidic
      type. The glucan also contains alpha-(1-->6)-linked glucosyl units and 4,6
      disubstituted alpha-glucosyl units at the branching points. Using degenerate
      primers, based on the amino acid sequences of conserved regions from known
      glucosyltransferase (gtf) genes from lactic acid bacteria, the L. reuteri strain
      121 glucosyltransferase gene (gtfA) was isolated. The gtfA open reading frame
      (ORF) was 5,343 bp, and it encodes a protein of 1,781 amino acids with a deduced
      M(r) of 198,637. The deduced amino acid sequence of GTFA revealed clear
      similarities with other glucosyltransferases. GTFA has a relatively large
      variable N-terminal domain (702 amino acids) with five unique repeats and a
      relatively short C-terminal domain (267 amino acids). The gtfA gene was expressed
      in Escherichia coli, yielding an active GTFA enzyme. With respect to binding type
      and size distribution, the recombinant GTFA enzyme and the L. reuteri strain 121
      culture supernatants synthesized identical glucan polymers. Furthermore, the
      deduced amino acid sequence of the gtfA ORF and the N-terminal amino acid
      sequence of the glucosyltransferase isolated from culture supernatants of L.
      reuteri strain 121 were the same. GTFA is thus responsible for the synthesis of
      the unique glucan polymer in L. reuteri strain 121. This is the first report on
      the molecular characterization of a glucosyltransferase from a Lactobacillus
      strain.

PMID- 12200278
TI  - The fibronectin type 3-like repeat from the Clostridium thermocellum
      cellobiohydrolase CbhA promotes hydrolysis of cellulose by modifying its surface.
AB  - Fibronectin type 3 homology domains (Fn3) as found in the cellobiohydrolase CbhA
      of Clostridium thermocellum are common among bacterial extracellular
      glycohydrolases. The function of these domains is not clear. CbhA is modular and
      composed of an N-terminal family IV carbohydrate-binding domain (CBDIV), an
      immunoglobulin-like domain, a family 9 glycosyl hydrolase catalytic domain (Gh9),
      two Fn3-like domains (Fn3(1,2)), a family III carbohydrate-binding domain
      (CBDIII), and a dockerin domain. Efficiency of cellulose hydrolysis by truncated
      forms of CbhA increased in the following order: Gh9 (lowest efficiency), Gh9
      Fn3(1,2) (more efficient), and Gh9-Fn3(1,2)-CBDIII (greatest efficiency).
      Thermostability of the above constructs decreased in the following order: Gh9
      (most stable), Gh9-Fn3(1,2), and then Gh9-Fn3(1,2)-CBDIII (least stable). Mixing
      of Orpinomyces endoglucanase CelE with Fn3(1,2,) or Fn3(1,2)-CBDIII increased
      efficiency of hydrolysis of acid-swollen cellulose (ASC) and filter paper.
      Scanning electron microscopic studies of filter paper treated with Fn3(1,2),
      Fn3(1,2)-CBDIII, or CBDIII showed that the surface of the cellulose fibers had
      been loosened up and crenellated by Fn3(1,2) and Fn3(1,2)-CBDIII and to a lesser
      extent by CBDIII. X-ray diffraction analysis did not reveal changes in the
      crystallinity of the filter paper. CBDIII bound to ASC and filter paper with
      capacities of 2.45 and 0.73 micro moles g(-1) and relative affinities (K(r)) of
      1.12 and 2.13 liters g(-1), respectively. Fn3(1,2) bound weakly to both
      celluloses. Fn3(1,2)-CBD bound to ASC and filter paper with capacities of 3.22
      and 0.81 micro moles g(-1) and K(r)s of 1.14 and 1.98 liters g(-1), respectively.
      Fn3(1,2) and CBDIII contained 2 and 1 mol of calcium per mol, respectively. The
      results suggest that Fn3(1,2) aids the hydrolysis of cellulose by modifying its
      surface. This effect is enhanced by the presence of CBDIII, which increases the
      concentration of Fn3(1,2) on the cellulose surface.

PMID- 12200279
TI  - Isolation of antibiotics turbomycin a and B from a metagenomic library of soil
      microbial DNA.
AB  - To access the genetic and biochemical potential of soil microorganisms by culture
      independent methods, a 24,546-member library in Escherichia coli with DNA
      extracted directly from soil had previously been constructed (M. R. Rondon, P. R.
      August, A. D. Bettermann, S. F. Brady, T. H. Grossman, M. R. Liles, K. A.
      Loiacono, B. A. Lynch, I. A. MacNeil, M. S. Osburne, J. Clardy, J. Handelsman,
      and R. M. Goodman, Appl. Environ. Microbiol. 66:2541-2547, 2000). Three clones,
      P57G4, P89C8, and P214D2, produced colonies with a dark brown melanin-like color.
      We fractionated the culture supernatant of P57G4 to identify the pigmented
      compound or compounds. Methanol extracts of the acid precipitate from the culture
      supernatant contained a red and an orange pigment. Structural analysis revealed
      that these were triaryl cations, designated turbomycin A and turbomycin B,
      respectively; both exhibited broad-spectrum antibiotic activity against gram
      negative and gram-positive organisms. Mutagenesis, subcloning, and sequence
      analysis of the 25-kb insert in P57G4 demonstrated that a single open reading
      frame was necessary and sufficient to confer production of the brown, orange, and
      red pigments on E. coli; the predicted product of this sequence shares extensive
      sequence similarity with members of the 4-hydroxyphenylpyruvate dioxygenase
      (4HPPD) family of enzymes. Another member of the same family of genes, lly, which
      is required for production of the hemolytic pigment in Legionella pneumophila,
      also conferred production of turbomycin A and B on E. coli. We further
      demonstrated that turbomycin A and turbomycin B are produced from the interaction
      of indole, normally secreted by E. coli, with homogentisic acid synthesized by
      the 4HPPD gene products. The results demonstrate successful heterologous
      expression of DNA extracted directly from soil as a means to access previously
      uncharacterized small organic compounds, serving as an example of a chimeric
      pathway for the generation of novel chemical structures.

PMID- 12200280
TI  - Seasonal variation in lysogeny as depicted by prophage induction in Tampa Bay,
      Florida.
AB  - A seasonal study of the distribution of lysogenic bacteria in Tampa Bay, Florida,
      was conducted over a 13-month period. Biweekly water samples were collected and
      either were left unaltered or had the viral population reduced by filtration
      (pore size, 0.2 micro m) and resuspension in filtered (pore size, 0.2 micro m)
      water. Virus-reduced and unaltered samples were then treated by adding mitomycin
      C (0.5 micro g ml(-1)) to induce prophage or were left untreated. In order to
      test the hypothesis that prophage induction was phosphate limited, additional
      induction experiments were performed in the presence and absence of phosphate.
      Induction was assessed as an increase in viral direct counts, relative to those
      obtained in controls, as detected by epifluorescence microscopy. Induction of
      prophage was observed in 5 of 25 (20%) unaltered samples which were obtained
      during or after the month of February, paralleling the results from a previous
      seasonal study. Induction of prophage was observed in 9 of 25 (36%) of the virus
      reduced samples, primarily those obtained in the winter months, which was not
      observed in a prior seasonal study (P. K. Cochran and J. H. Paul, Appl. Environ.
      Microbiol. 64:2308-2312, 1998). Induction was noted in the months of lowest
      bacterial and primary production, suggesting that lysogeny was favored under
      conditions of poor host growth. Phosphate addition enabled prophage induction in
      two of nine (22%) experiments. These results indicate that prophage induction may
      occasionally be phosphate limited or respond to increases in phosphate
      concentration, suggesting that phosphate concentration may modulate the lysogenic
      response of natural populations.

PMID- 12200281
TI  - Biotransformation of eugenol to ferulic acid by a recombinant strain of Ralstonia
      eutropha H16.
AB  - The gene loci ehyAB, calA, and calB, encoding eugenol hydroxylase, coniferyl
      alcohol dehydrogenase, and coniferyl aldehyde dehydrogenase, respectively, which
      are involved in the first steps of eugenol catabolism in Pseudomonas sp. strain
      HR199, were amplified by PCR and combined to construct a catabolic gene cassette.
      This gene cassette was cloned in the newly designed broad-host-range vector pBBR1
      JO2 (pBBR1-JO2ehyABcalAcalB) and transferred to Ralstonia eutropha H16. A
      recombinant strain of R. eutropha H16 harboring this plasmid expressed
      functionally active eugenol hydroxylase, coniferyl alcohol dehydrogenase, and
      coniferyl aldehyde dehydrogenase. Cells of R. eutropha H16(pBBR1
      JO2ehyABcalAcalB) from the late-exponential growth phase were used as
      biocatalysts for the biotransformation of eugenol to ferulic acid. A maximum
      conversion rate of 2.9 mmol of eugenol per h per liter of culture was achieved
      with a yield of 93.8 mol% of ferulic acid from eugenol within 20 h, without
      further optimization.

PMID- 12200282
TI  - Lactobacillus plantarum MiLAB 393 produces the antifungal cyclic dipeptides
      cyclo(L-Phe-L-Pro) and cyclo(L-Phe-trans-4-OH-L-Pro) and 3-phenyllactic acid.
AB  - We have isolated a Lactobacillus plantarum strain (MiLAB 393) from grass silage
      that produces broad-spectrum antifungal compounds, active against food- and feed
      borne filamentous fungi and yeasts in a dual-culture agar plate assay. Fusarium
      sporotrichioides and Aspergillus fumigatus were the most sensitive among the
      molds, and Kluyveromyces marxianus was the most sensitive yeast species. No
      inhibitory activity could be detected against the mold Penicillium roqueforti or
      the yeast Zygosaccharomyces bailii. An isolation procedure, employing a
      microtiter well spore germination bioassay, was devised to isolate active
      compounds from culture filtrate. Cell-free supernatant was fractionated on a
      C(18) SPE column, and the 95% aqueous acetonitrile fraction was further separated
      on a preparative HPLC C(18) column. Fractions active in the bioassay were then
      fractionated on a porous graphitic carbon column. The structures of the
      antifungal compounds cyclo(L-Phe-L-Pro), cyclo(L-Phe-trans-4-OH-L-Pro) and 3
      phenyllactic acid (L/D isomer ratio, 9:1), were determined by nuclear magnetic
      resonance spectroscopy, mass spectrometry, and gas chromatography. MIC values
      against A. fumigatus and P. roqueforti were 20 mg ml(-1) for cyclo(L-Phe-L-Pro)
      and 7.5 mg ml(-1) for phenyllactic acid. Combinations of the antifungal compounds
      revealed weak synergistic effects. The production of the antifungal cyclic
      dipeptides cyclo(L-Phe-L-Pro) and cyclo(L-Phe-trans-4-OH-L-Pro) by lactic acid
      bacteria is reported here for the first time.

PMID- 12200283
TI  - Hydroxyectoine is superior to trehalose for anhydrobiotic engineering of
      Pseudomonas putida KT2440.
AB  - Anhydrobiotic engineering aims to increase the level of desiccation tolerance in
      sensitive organisms to that observed in true anhydrobiotes. In addition to a
      suitable extracellular drying excipient, a key factor for anhydrobiotic
      engineering of gram-negative enterobacteria seems to be the generation of high
      intracellular concentrations of the nonreducing disaccharide trehalose, which can
      be achieved by osmotic induction. In the soil bacterium Pseudomonas putida
      KT2440, however, only limited amounts of trehalose are naturally accumulated in
      defined high-osmolarity medium, correlating with relatively poor survival of
      desiccated cultures. Based on the enterobacterial model, it was proposed that
      increasing intracellular trehalose concentration in P. putida KT2440 should
      improve survival. Using genetic engineering techniques, intracellular trehalose
      concentrations were obtained which were similar to or greater than those in
      enterobacteria, but this did not translate into improved desiccation tolerance.
      Therefore, at least for some populations of microorganisms, trehalose does not
      appear to provide full protection against desiccation damage, even when present
      at high concentrations both inside and outside the cell. For P. putida KT2440, it
      was shown that this was not due to a natural limit in desiccation tolerance since
      successful anhydrobiotic engineering was achieved by use of a different drying
      excipient, hydroxyectoine, with osmotically preconditioned bacteria for which 40
      to 60% viability was maintained over extended periods (up to 42 days) in the dry
      state. Hydroxyectoine therefore has considerable potential for the improvement of
      desiccation tolerance in sensitive microorganisms, particularly for those
      recalcitrant to trehalose.

PMID- 12200284
TI  - Role of tfxE, but not tfxG, in trifolitoxin resistance.
AB  - Eight genes, tfxABCDEFG and tfuA, confer production of trifolitoxin (TFX), a
      ribosomally synthesized, posttranslationally modified peptide antibiotic, in TFX
      sensitive alpha-proteobacteria. An in-frame deletion in tfxE significantly
      reduced a strain's resistance to TFX in comparison to that of an otherwise
      identical construct containing wild-type tfxE. The deletion of tfxG had no effect
      on TFX resistance. Nevertheless, RNase protection assays showed that tfxE and
      tfxG are transcribed, showing that the tfxDEFG mRNA was produced on the same
      transcript. Examination of the role of tfxG in TFX production showed that the
      tfxG mutant expressed slightly less TFX activity and produced only one TFX isomer
      while four are produced by the wild-type strain. Thus, tfxE plays an important
      role in TFX resistance while tfxG is important in optimal TFX production through
      the production of TFX isomers.

PMID- 12200285
TI  - Identification of quinoide redox mediators that are formed during the degradation
      of naphthalene-2-sulfonate by Sphingomonas xenophaga BN6.
AB  - During aerobic degradation of naphthalene-2-sulfonate (2NS), Sphingomonas
      xenophaga strain BN6 produces redox mediators which significantly increase the
      ability of the strain to reduce azo dyes under anaerobic conditions. It was
      previously suggested that 1,2-dihydroxynaphthalene (1,2-DHN), which is an
      intermediate in the degradative pathway of 2NS, is the precursor of these redox
      mediators. In order to analyze the importance of the formation of 1,2-DHN, the
      dihydroxynaphthalene dioxygenase gene (nsaC) was disrupted by gene replacement.
      The resulting strain, strain AKE1, did not degrade 2NS to salicylate. After
      aerobic preincubation with 2NS, strain AKE1 exhibited much higher reduction
      capacities for azo dyes under anaerobic conditions than the wild-type strain
      exhibited. Several compounds were present in the culture supernatants which
      enhanced the ability of S. xenophaga BN6 to reduce azo dyes under anaerobic
      conditions. Two major redox mediators were purified from the culture
      supernatants, and they were identified by high-performance liquid chromatography
      mass spectrometry and comparison with chemically synthesized standards as 4-amino
      1,2-naphthoquinone and 4-ethanolamino-1,2-naphthoquinone.

PMID- 12200286
TI  - Formation and conversion of oxygen metabolites by Lactococcus lactis subsp.
      lactis ATCC 19435 under different growth conditions.
AB  - A semidefined medium based on Casamino Acids allowed Lactococcus lactis ATCC
      19435 to grow in the presence of oxygen at a slow rate (0.015 h(-1)).
      Accumulation of H(2)O(2) in the culture prevented a higher growth rate. Addition
      of asparagine to the medium increased the growth rate, whereby H(2)O(2)
      accumulated only temporarily during the lag phase. H(2)O(2) is an inhibitor for
      several glycolytic enzymes, glyceraldehyde-3-phosphate dehydrogenase being the
      most sensitive. Strain ATCC 19435 contained NADH oxidase (maximum specific rate
      under aerobic conditions, 426 nmol of NADH min(-1) mg of protein(-1)), which
      reduced oxygen to water, whereby superoxide was formed as a by-product. H(2)O(2)
      originated from the dismutation of superoxide by superoxide dismutase. Although
      H(2)O(2) was rapidly destroyed under high metabolic fluxes, neither NADH
      peroxidase nor any other enzymatic H(2)O(2)-reducing activity was detected.
      However, pyruvate, the end product of glycolysis, reacted nonenzymatically and
      rapidly with H(2)O(2) and hence was a potential alternative for scavenging of
      this oxygen metabolite intracellularly. Indeed, intracellular concentrations of
      up to 93 mM pyruvate were detected in aerobic cultures growing at high rates. It
      is hypothesized that self-generated pyruvate may serve to protect L. lactis
      strain ATCC 19435 from H(2)O(2).

PMID- 12200287
TI  - Effects of high pressure on the viability, morphology, lysis, and cell wall
      hydrolase activity of Lactococcus lactis subsp. cremoris.
AB  - Viability, morphology, lysis, and cell wall hydrolase activity of Lactococcus
      lactis subsp. cremoris MG1363 and SK11 were determined after exposure to
      pressure. Both strains were completely inactivated at pressures of 400 to 800 MPa
      but unaffected at 100 and 200 MPa. At 300 MPa, the MG1363 and SK11 populations
      decreased by 7.3 and 2.5 log cycles, respectively. Transmission electron
      microscopy indicated that pressure caused intracellular and cell envelope damage.
      Pressure-treated MG1363 cell suspensions lysed more rapidly over time than did
      non-pressure-treated controls. Twenty-four hours after pressure treatment, the
      percent lysis ranged from 13.0 (0.1 MPa) to 43.3 (300 MPa). Analysis of the
      MG1363 supernatants by sodium dodecyl sulfate-polyacrylamide gel electrophoresis
      (SDS-PAGE) confirmed pressure-induced lysis. Pressure did not induce lysis or
      membrane permeability of SK11. Renaturing SDS-PAGE (zymogram analysis) revealed
      two hydrolytic bands from MG1363 cell extracts treated at all pressures (0.1 to
      800 MPa). Measuring the reducing sugars released during enzymatic cell wall
      breakdown provided a quantitative, nondenaturing assay of cell wall hydrolase
      activity. Cells treated at 100 MPa released significantly more reducing sugar
      than other samples, including the non-pressure-treated control, indicating that
      pressure can activate cell wall hydrolase activity or increase cell wall
      accessibility to the enzyme. The cell suspensions treated at 200 and 300 MPa did
      not differ significantly from the control, whereas cells treated at pressures
      greater than 400 MPa displayed reduced cell wall hydrolase activity. These data
      suggest that high pressure can cause inactivation, physical damage, and lysis in
      L. lactis. Pressure-induced lysis is strain dependent and not solely dependent
      upon cell wall hydrolase activity.

PMID- 12200288
TI  - Effect of exopolysaccharides on phage-host interactions in Lactococcus lactis.
AB  - In this study, we report that Lactococcus lactis strains producing
      exopolysaccharides (EPS) are sensitive to virulent phages. Eight distinct lytic
      phages (Q61 to Q68) specifically infecting Eps(+) strains were isolated in 47
      buttermilk samples obtained from 13 North American factories. The eight phages
      were classified within the 936 species by the multiplex PCR method, indicating
      that these phages are not fundamentally distinct from those infecting Eps(-) L.
      lactis strains. The host range of these phages was determined with 19 Lactococcus
      strains, including 7 Eps(+) and 12 Eps(-) cultures. Three phages (Q62, Q63, and
      Q64) attacked only the Eps(+) strain SMQ-419, whereas the five other phages (Q61,
      Q65, Q66, Q67, and Q68) infected only the Eps(+) strain SMQ-420. The five other
      Eps(+) strains (H414, MLT2, MLT3, SMQ-461, and SMQ-575) as well as the 12 Eps(-)
      strains were insensitive to these phages. The monosaccharide composition of the
      polymer produced by the seven Eps(+) strains was determined. The EPS produced by
      strains MLT3, SMQ-419, and SMQ-575 contained glucose, galactose, and rhamnose.
      The EPS fabricated by H414 contained only galactose. The EPS made by MLT2, SMQ
      420, and SMQ-461 contained glucose and galactose. These findings indicate that
      the sugar composition of the EPS has no effect on phage sensitivity. The plasmid
      encoding the eps operon was cured from the two phage-sensitive strains. The cured
      derivatives were still phage sensitive, which indicates that EPS are not
      necessary for phage infection. Phage adsorption assays showed that the production
      of EPS does not confer a significant phage resistance phenotype.

PMID- 12200289
TI  - Influence of elevated CO(2) on the fungal community in a coastal scrub oak forest
      soil investigated with terminal-restriction fragment length polymorphism
      analysis.
AB  - Sixteen open-top chambers (diameter, 3.66 m) were established in a scrub oak
      habitat in central Florida where vegetation was removed in a planned burn prior
      to chamber installation. Eight control chambers have been continuously exposed to
      ambient air and eight have been continuously exposed to elevated CO(2) at twice
      ambient concentration (approximately 700 ppm) for 5 years. Soil cores were
      collected from each chamber to examine the influence of elevated atmospheric
      CO(2) on the fungal community in different soil fractions. Each soil sample was
      physically fractionated into bulk soil, rhizosphere soil, and roots for separate
      analyses. Changes in relative fungal biomass were estimated by the ergosterol
      technique. In the bulk soil and root fractions, a significantly increased level
      of ergosterol was detected in the elevated CO(2) treatments relative to ambient
      controls. Fungal community composition was determined by terminal-restriction
      fragment length polymorphism (T-RFLP) analysis of the internal transcribed spacer
      (ITS) region. The specificities of different ITS primer sets were evaluated
      against plant and fungal species isolated from the experimental site. Changes in
      community composition were assessed by principal component analyses of T-RFLP
      profiles resolved by capillary electrophoresis. Fungal species richness, defined
      by the total number of terminal restriction fragments, was not significantly
      affected by either CO(2) treatment or soil fraction.

PMID- 12200290
TI  - Influence of tropolone on Poria placenta wood degradation.
AB  - Fenton reactions are believed to play important roles in wood degradation by
      brown rot fungi. In this context, the effect of tropolone (2-hydroxycyclohepta
      2,4,6-trienone), a metal chelator, on wood degradation by Poria placenta was
      investigated. Tropolone (50 micro M) strongly inhibits fungal growth on malt
      agar, but this inhibition could be relieved by adding iron salts. With an
      experimental system containing two separate parts, one supplemented with
      tropolone (100 micro M) and the other not, it was shown that the fungus is able
      to reallocate essential minerals from the area where they are available and also
      to grow in these conditions on malt-agar in the presence of tropolone.
      Nevertheless, even in the presence of an external source of metals, P. placenta
      is not able to attack pine blocks impregnated with tropolone (5 mM). This wood
      degradation inhibition is related to the presence of the tropolone hydroxyl
      group, as shown by the use of analogs (cyclohepta-2,4,6-trienone and 2
      methoxycyclohepta-2,4,6-trienone). Furthermore, tropolone possesses both weak
      antioxidative and weak radical-scavenging properties and a strong affinity for
      ferric ion and is able to inhibit ferric iron reduction by catecholates, lowering
      the redox potential of the iron couple. These data are consistent with the
      hypothesis that tropolone inhibits wood degradation by P. placenta by chelating
      iron present in wood, thus avoiding initiation of the Fenton reaction. This study
      demonstrates that iron chelators such as tropolone could be also involved in
      novel and more environmentally benign preservative systems.

PMID- 12200291
TI  - Assessment of the importance of similarity in carbon source utilization profiles
      between the biological control agent and the pathogen in biological control of
      bacterial speck of tomato.
AB  - Bacterial speck of tomato, caused by Pseudomonas syringae pv. tomato, was used to
      determine whether similarity in carbon source utilization between a preemptive
      biological control agent and the pathogen was significant in determining the
      ability of the bacterium to suppress disease. Similarity in carbon source
      utilization was quantified as the ratio of the number of tomato carbon sources
      utilized in vitro by the biological control agent to the number of tomato carbon
      sources utilized in vitro by the target pathogen (the niche overlap index [NOI]).
      Suppression of the disease was quantified as the percent reduction in disease
      severity compared to the pathogen-only control when nonpathogenic bacteria were
      applied to foliage 48 h prior to the pathogen. In the collection of 36
      nonpathogenic bacterial strains, there was a significant (P < 0.01), but weak
      (r(2) = 0.25), correlation between reduction in disease severity and similarity
      in carbon source utilization, suggesting that similarity in carbon source use was
      significant in determining ability to suppress disease. The relationship was
      investigated further using catabolic mutants of P. syringae strain TLP2, an
      effective biological control agent of speck. Catabolic mutants exhibited lower
      levels of similarity (NOI = 0.07 to 0.90) than did wild-type TLP2 (NOI = 0.93).
      With these catabolic mutants there was a significant (P < 0.01), and stronger
      (r(2) = 0.42), correlation between reduction in disease severity and similarity
      in carbon source utilization. This suggests that similarity in carbon source
      utilization was a more important component of biological control ability for the
      catabolic mutants than for the nonpathogenic bacteria. Together, these studies
      indicate that suppression of bacterial speck of tomato was correlated with
      nutritional similarity between the pathogenic and nonpathogenic bacteria and
      suggest that preemptive utilization of carbon sources was probably involved in
      the biological control of the disease by both the naturally occurring
      nonpathogenic bacteria and the catabolic mutants.

PMID- 12200292
TI  - Characterization of a novel fructosyltransferase from Lactobacillus reuteri that
      synthesizes high-molecular-weight inulin and inulin oligosaccharides.
AB  - Fructosyltransferase (FTF) enzymes produce fructose polymers (fructans) from
      sucrose. Here, we report the isolation and characterization of an FTF-encoding
      gene from Lactobacillus reuteri strain 121. A C-terminally truncated version of
      the ftf gene was successfully expressed in Escherichia coli. When incubated with
      sucrose, the purified recombinant FTF enzyme produced large amounts of fructo
      oligosaccharides (FOS) with beta-(2-->1)-linked fructosyl units, plus a high
      molecular-weight fructan polymer (>10(7)) with beta-(2-->1) linkages (an inulin).
      FOS, but not inulin, was found in supernatants of L. reuteri strain 121 cultures
      grown on medium containing sucrose. Bacterial inulin production has been reported
      for only Streptococcus mutans strains. FOS production has been reported for a few
      bacterial strains. This paper reports the first-time isolation and molecular
      characterization of (i) a Lactobacillus ftf gene, (ii) an inulosucrase associated
      with a generally regarded as safe bacterium, (iii) an FTF enzyme synthesizing
      both a high molecular weight inulin and FOS, and (iv) an FTF protein containing a
      cell wall-anchoring LPXTG motif. The biological relevance and potential health
      benefits of an inulosucrase associated with an L. reuteri strain remain to be
      established.

PMID- 12200293
TI  - In situ determination of the intracellular pH of Lactococcus lactis and
      Lactobacillus plantarum during pressure treatment.
AB  - Hydrostatic pressure may affect the intracellular pH of microorganisms by (i)
      enhancing the dissociation of weak organic acids and (ii) increasing the
      permeability of the cytoplasmic membrane and inactivation of enzymes required for
      pH homeostasis. The internal pHs of Lactococcus lactis and Lactobacillus
      plantarum during and after pressure treatment at 200 and 300 MPa and at pH values
      ranging from 4.0 to 6.5 were determined. Pressure treatment at 200 MPa for up to
      20 min did not reduce the viability of either strain at pH 6.5. Pressure
      treatment at pH 6.5 and 300 MPa reduced viable cell counts of Lactococcus lactis
      and Lactobacillus plantarum by 5 log after 20 and 120 min, respectively. Pressure
      inactivation was faster at pH 5 or 4. At ambient pressure, both strains
      maintained a transmembrane pH gradient of 1 pH unit at neutral pH and about 2 pH
      units at pH 4.0. During pressure treatment at 200 and 300 MPa, the internal pH of
      L. lactis was decreased to the value of the extracellular pH during compression.
      The same result was observed during treatment of Lactobacillus plantarum at 300
      MPa. Lactobacillus plantarum was unable to restore the internal pH after a
      compression-decompression cycle at 300 MPa and pH 6.5. Lactococcus lactis lost
      the ability to restore its internal pH after 20 and 4 min of pressure treatment
      at 200 and 300 MPa, respectively. As a consequence, pressure-mediated stress
      reactions and cell death may be considered secondary effects promoted by pH and
      other environmental conditions.

PMID- 12200294
TI  - Characterization of the 5-carboxyvanillate decarboxylase gene and its role in
      lignin-related biphenyl catabolism in Sphingomonas paucimobilis SYK-6.
AB  - Sphingomonas paucimobilis SYK-6 degrades a lignin-related biphenyl compound, 5,5'
      dehydrodivanillate (DDVA), to 5-carboxyvanillate (5CVA) by the enzyme reactions
      catalyzed by the DDVA O-demethylase (LigX), the ring cleavage oxygenase (LigZ),
      and the meta-cleavage compound hydrolase (LigY). In this study we examined the
      degradation step of 5CVA. 5CVA was transformed to vanillate, O-demethylated, and
      further degraded via the protocatechuate 4,5-cleavage pathway by this strain. A
      cosmid clone which conferred the 5CVA degradation activity to a host strain was
      isolated. In the 7.0-kb EcoRI fragment of the cosmid we found a 1,002-bp open
      reading frame responsible for the conversion of 5CVA to vanillate, and we
      designated it ligW. The gene product of ligW (LigW) catalyzed the decarboxylation
      of 5CVA to produce vanillate along with the specific incorporation of deuterium
      from deuterium oxide, indicating that LigW is a nonoxidative decarboxylase of
      5CVA. LigW did not require any metal ions or cofactors for its activity. The
      decarboxylase activity was specific to 5CVA. Inhibition experiments with 5CVA
      analogs suggested that two carboxyl groups oriented meta to each other in 5CVA
      are important to the substrate recognition by LigW. Gene walking analysis
      indicated that the ligW gene was located on the 18-kb DNA region with other DDVA
      catabolic genes, including ligZ, ligY, and ligX.

PMID- 12200295
TI  - Cloning and characterization of the ferulic acid catabolic genes of Sphingomonas
      paucimobilis SYK-6.
AB  - Sphingomonas paucimobilis SYK-6 degrades ferulic acid to vanillin, and it is
      further metabolized through the protocatechuate 4,5-cleavage pathway. We obtained
      a Tn5 mutant of SYK-6, FA2, which was able to grow on vanillic acid but not on
      ferulic acid. A cosmid which complemented the growth deficiency of FA2 on ferulic
      acid was isolated. The 5.2-kb BamHI-EcoRI fragment in this cosmid conferred the
      transformation activity of ferulic acid to vanillin on Escherichia coli host
      cells. A sequencing analysis revealed the genes ferB and ferA in this fragment;
      these genes consist of 852- and 2,127-bp open reading frames, respectively. The
      deduced amino acid sequence of ferB showed 40 to 48% identity with that of the
      feruloyl-coenzyme A (CoA) hydratase/lyase genes of Pseudomonas and Amycolatopsis
      ferulic acid degraders. On the other hand, the deduced amino acid sequence of
      ferA showed no significant similarity to the feruloyl-CoA synthetase genes of
      other ferulic acid degraders. However, the deduced amino acid sequence of ferA
      did show 31% identity with pimeloyl-CoA synthetase of Pseudomonas mendocina 35,
      which has been classified as a new superfamily of acyl-CoA synthetase (ADP
      forming) with succinyl-CoA synthetase (L. B. Sanchez, M. Y. Galperin, and M.
      Muller, J. Biol. Chem. 275:5794-5803, 2000). On the basis of the enzyme activity
      of E. coli carrying each of these genes, ferA and ferB were shown to encode a
      feruloyl-CoA synthetase and feruloyl-CoA hydratase/lyase, respectively. p
      coumaric acid, caffeic acid, and sinapinic acid were converted to their
      corresponding benzaldehyde derivatives by the cell extract containing FerA and
      FerB, thereby indicating their broad substrate specificities. We found a ferB
      homolog, ferB2, upstream of a 5-carboxyvanillic acid decarboxylase gene (ligW)
      involved in the degradation of 5,5'-dehydrodivanillic acid. The deduced amino
      acid sequence of ferB2 showed 49% identity with ferB, and its gene product showed
      feruloyl-CoA hydratase/lyase activity with a substrate specificity similar to
      that of FerB. Insertional inactivation of each fer gene in S. paucimobilis SYK-6
      suggested that the ferA gene is essential and that ferB and ferB2 genes are
      involved in ferulic acid degradation.

PMID- 12200296
TI  - Environmental factors that control microbial perchlorate reduction.
AB  - As part of a study to elucidate the environmental parameters that control
      microbial perchlorate respiration, we investigated the reduction of perchlorate
      by the dissimilatory perchlorate reducer Dechlorosoma suillum under a diverse set
      of environmental conditions. Our results demonstrated that perchlorate reduction
      by D. suillum only occurred under anaerobic conditions in the presence of
      perchlorate and was dependent on the presence of molybdenum. Perchlorate
      reduction was dependent on the presence of the enzyme chlorite dismutase, which
      was induced during metabolism of perchlorate. Anaerobic conditions alone were not
      enough to induce expression of this enzyme. Dissolved oxygen concentrations less
      than 2 mg liter(-1) were enough to inhibit perchlorate reduction by D. suillum.
      Similarly to oxygen, nitrate also regulated chlorite dismutase expression and
      repressed perchlorate reduction by D. suillum. Perchlorate-grown cultures of D.
      suillum preferentially reduced nitrate in media with equimolar amounts of
      perchlorate and nitrate. In contrast, an extended (40 h) lag phase was observed
      if a similar nitrate-perchlorate medium was inoculated with a nitrate-grown
      culture. Perchlorate reduction commenced only when nitrate was completely removed
      in either of these experiments. In contrast to D. suillum, nitrate had no
      inhibitory effects on perchlorate reduction by the perchlorate reducer
      Dechloromonas agitata strain CKB. Nitrate was reduced to nitrite concomitant with
      perchlorate reduction to chloride. These studies demonstrate that microbial
      respiration of perchlorate is significantly affected by environmental conditions
      and perchlorate reduction is directly dependent on bioavailable molybdenum and
      the presence or absence of competing electron acceptors. A microbial treatment
      strategy can achieve and maintain perchlorate concentrations below the
      recommended regulatory level, but only in environments in which the variables
      described above can be controlled.

PMID- 12200297
TI  - Molecular evidence for a uniform microbial community in sponges from different
      oceans.
AB  - Sponges (class Porifera) are evolutionarily ancient metazoans that populate the
      tropical oceans in great abundances but also occur in temperate regions and even
      in freshwater. Sponges contain large numbers of bacteria that are embedded within
      the animal matrix. The phylogeny of these bacteria and the evolutionary age of
      the interaction are virtually unknown. In order to provide insights into the
      species richness of the microbial community of sponges, we performed a
      comprehensive diversity survey based on 190 sponge-derived 16S ribosomal DNA
      (rDNA) sequences. The sponges Aplysina aerophoba and Theonella swinhoei were
      chosen for construction of the bacterial 16S rDNA library because they are
      taxonomically distantly related and they populate nonoverlapping geographic
      regions. In both sponges, a uniform microbial community was discovered whose
      phylogenetic signature is distinctly different from that of marine plankton or
      marine sediments. Altogether 14 monophyletic, sponge-specific sequence clusters
      were identified that belong to at least seven different bacterial divisions. By
      definition, the sequences of each cluster are more closely related to each other
      than to a sequence from nonsponge sources. These monophyletic clusters comprise
      70% of all publicly available sponge-derived 16S rDNA sequences, reflecting the
      generality of the observed phenomenon. This shared microbial fraction represents
      the smallest common denominator of the sponges investigated in this study.
      Bacteria that are exclusively found in certain host species or that occur only
      transiently would have been missed. A picture emerges where sponges can be viewed
      as highly concentrated reservoirs of so far uncultured and elusive marine
      microorganisms.

PMID- 12200298
TI  - Effect of modified atmosphere composition on the metabolism of glucose by
      Brochothrix thermosphacta.
AB  - The influence of atmosphere composition on the metabolism of Brochothrix
      thermosphacta was studied by analyzing the consumption of glucose and the
      production of ethanol, acetic and lactic acids, acetaldehyde, and diacetyl
      acetoin under atmospheres containing different combinations of carbon dioxide and
      oxygen. When glucose was metabolized under oxygen-free atmospheres, lactic acid
      was one of the main end products, while under atmospheres rich in oxygen mainly
      acetoin-diacetyl was produced. The proportions of the total consumed glucose used
      for the production of acetoin (aerobic metabolism) and lactic acid (anaerobic
      metabolism) were used to decide whether aerobic or anaerobic metabolism
      predominated at a given atmosphere composition. The boundary conditions between
      dominantly anaerobic and aerobic metabolisms were determined by logistic
      regression. The metabolism of glucose by B. thermosphacta was influenced not only
      by the oxygen content of the atmosphere but also by the carbon dioxide content.
      At high CO(2) percentages, glucose metabolism remained anaerobic under greater
      oxygen contents.

PMID- 12200299
TI  - Metabolic control analysis of glycerol synthesis in Saccharomyces cerevisiae.
AB  - Glycerol, a major by-product of ethanol fermentation by Saccharomyces cerevisiae,
      is of significant importance to the wine, beer, and ethanol production
      industries. To gain a clearer understanding of and to quantify the extent to
      which parameters of the pathway affect glycerol flux in S. cerevisiae, a kinetic
      model of the glycerol synthesis pathway has been constructed. Kinetic parameters
      were collected from published values. Maximal enzyme activities and intracellular
      effector concentrations were determined experimentally. The model was validated
      by comparing experimental results on the rate of glycerol production to the rate
      calculated by the model. Values calculated by the model agreed well with those
      measured in independent experiments. The model also mimics the changes in the
      rate of glycerol synthesis at different phases of growth. Metabolic control
      analysis values calculated by the model indicate that the NAD(+)-dependent
      glycerol 3-phosphate dehydrogenase-catalyzed reaction has a flux control
      coefficient (C(J)v1) of approximately 0.85 and exercises the majority of the
      control of flux through the pathway. Response coefficients of parameter
      metabolites indicate that flux through the pathway is most responsive to
      dihydroxyacetone phosphate concentration (R(J)DHAP= 0.48 to 0.69), followed by
      ATP concentration (R(J)ATP = -0.21 to -0.50). Interestingly, the pathway responds
      weakly to NADH concentration (R(J)NADH = 0.03 to 0.08). The model indicates that
      the best strategy to increase flux through the pathway is not to increase enzyme
      activity, substrate concentration, or coenzyme concentration alone but to
      increase all of these parameters in conjunction with each other.

PMID- 12200300
TI  - Influence of hydrodynamics and cell signaling on the structure and behavior of
      Pseudomonas aeruginosa biofilms.
AB  - Biofilms were grown from wild-type (WT) Pseudomonas aeruginosa PAO1 and the cell
      signaling lasI mutant PAO1-JP1 under laminar and turbulent flows to investigate
      the relative contributions of hydrodynamics and cell signaling for biofilm
      formation. Various biofilm morphological parameters were quantified using Image
      Structure Analyzer software. Multivariate analysis demonstrated that both cell
      signaling and hydrodynamics significantly (P < 0.000) influenced biofilm
      structure. In turbulent flow, both biofilms formed streamlined patches, which in
      some cases developed ripple-like wave structures which flowed downstream along
      the surface of the flow cell. In laminar flow, both biofilms formed monolayers
      interspersed with small circular microcolonies. Ripple-like structures also
      formed in four out of six WT biofilms, although their velocity was approximately
      10 times less than that of those that formed in the turbulent flow cells. The
      movement of biofilm cell clusters over solid surfaces may have important clinical
      implications for the dissemination of biofilm subject to fluid shear, such as
      that found in catheters. The ability of the cell signaling mutant to form
      biofilms in high shear flow demonstrates that signaling mechanisms are not
      required for the formation of strongly adhered biofilms. Similarity between
      biofilm morphologies in WT and mutant biofilms suggests that the dilution of
      signal molecules by mass transfer effects in faster flowing systems mollifies the
      dramatic influence of signal molecules on biofilm structure reported in previous
      studies.

PMID- 12200301
TI  - Optimization of bacteriocin production by batch fermentation of Lactobacillus
      plantarum LPCO10.
AB  - Optimization of bacteriocin production by Lactobacillus plantarum LPCO10 was
      explored by an integral statistical approach. In a prospective series of
      experiments, glucose and NaCl concentrations in the culture medium, inoculum
      size, aeration of the culture, and growth temperature were statistically combined
      using an experimental 2(3)(5-2) fractional factorial two-level design and tested
      for their influence on maximal bacteriocin production by L. plantarum LPCO10.
      After the values for the less-influential variables were fixed, NaCl
      concentration, inoculum size, and temperature were selected to study their
      optimal relationship for maximal bacteriocin production. This was achieved by a
      new experimental 3(2)(3-1) fractional factorial three-level design which was
      subsequently used to build response surfaces and analyzed for both linear and
      quadratic effects. Results obtained indicated that the best conditions for
      bacteriocin production were shown with temperatures ranging from 22 to 27 degrees
      C, salt concentration from 2.3 to 2.5%, and L. plantarum LPCO10 inoculum size
      ranging from 10(7.3) to 10(7.4) CFU/ml, fixing the initial glucose concentration
      at 2%, with no aeration of the culture. Under these optimal conditions, about 3.2
      x 10(4) times more bacteriocin per liter of culture medium was obtained than that
      used to initially purify plantaricin S from L. plantarum LPCO10 to homogeneity.
      These results indicated the importance of this study in obtaining maximal
      production of bacteriocins from L. plantarum LPCO10 so that bacteriocins can be
      used as preservatives in canned foods.

PMID- 12200302
TI  - Molecular evolution of aromatic polyketides and comparative sequence analysis of
      polyketide ketosynthase and 16S ribosomal DNA genes from various streptomyces
      species.
AB  - A 613-bp fragment of an essential ketosynthase gene from the biosynthetic pathway
      of aromatic polyketide antibiotics was sequenced from 99 actinomycetes isolated
      from soil. Phylogenetic analysis showed that the isolates clustered into clades
      that correspond to the various classes of aromatic polyketides. Additionally,
      sequencing of a 120-bp fragment from the gamma-variable region of 16S ribosomal
      DNA (rDNA) and subsequent comparative sequence analysis revealed incongruity
      between the ketosynthase and 16S rDNA phylogenetic trees, which strongly suggests
      that there has been horizontal transfer of aromatic polyketide biosynthesis
      genes. The results show that the ketosynthase tree could be used for DNA
      fingerprinting of secondary metabolites and for screening interesting aromatic
      polyketide biosynthesis genes. Furthermore, the movement of the ketosynthase
      genes suggests that traditional marker molecules like 16S rDNA give misleading
      information about the biosynthesis potential of aromatic polyketides, and thus
      only molecules that are directly involved in the biosynthesis of secondary
      metabolites can be used to gain information about the biodiversity of antibiotic
      production in different actinomycetes.

PMID- 12200303
TI  - Soil-atmosphere CO exchanges and microbial biogeochemistry of CO transformations
      in a Brazilian agricultural ecosystem.
AB  - Although anthropogenic land use has major impacts on the exchange of soil and
      atmosphere gas in general, relatively little is known about its impacts on carbon
      monoxide. We compared soil-atmosphere CO exchanges as a function of land use,
      crop type, and tillage treatment on an experimental farm in Parana, Brazil, that
      is representative of regionally important agricultural ecosystems. Our results
      showed that cultivated soils consumed CO at rates between 3 and 6 mg of CO m(-2)
      day(-1), with no statistically significant effect of tillage method or crop.
      However, CO exchange for a pasture soil was near zero, and an unmanaged woodlot
      emitted CO at a rate of 9 mg of CO m(-2) day(-1). Neither nitrite, aluminum
      sulfate, nor methyl fluoride additions affected CO consumption by tilled or
      untilled soils from soybean plots, indicating that CO oxidation did not depend on
      ammonia oxidizers and that CO oxidation patterns differed in part from patterns
      reported for forest soils. The apparent K(m) for CO uptake, 5 to 11 ppm, was
      similar to values reported for temperate forest soils; V(max) values,
      approximately 1 micro g of CO g (dry weight)(-1) h(-1), were comparable for
      woodlot and cultivated soils in spite of the fact that the latter consumed CO
      under ambient conditions. Short-term (24-h) exposure to elevated levels of CO
      (10% CO) partially inhibited uptake at lower concentrations (i.e., 100 ppm),
      suggesting that the sensitivity to CO of microbial populations that are active in
      situ differs from that of known carboxydotrophs. Soil-free soybean and corn roots
      consumed CO when they were incubated with 100-ppm concentrations and produced CO
      when they were incubated with ambient concentrations. These results document for
      the first time a role for cultivated plant roots in the dynamics of CO in an
      agricultural ecosystem.

PMID- 12200304
TI  - Quantitative tracing, by Taq nuclease assays, of a synechococcus ecotype in a
      highly diversified natural population.
AB  - Quantitative Taq nuclease assays (TNAs) (TaqMan PCR), nested PCR in combination
      with denaturing gradient gel electrophoresis (DGGE), and epifluorescence
      microscopy were used to analyze the autotrophic picoplankton (APP) of Lake
      Constance. Microscopic analysis revealed dominance of phycoerythrin (PE)-rich
      Synechococcus spp. in the pelagic zone of this lake. Cells passing a 3- micro m
      pore-size filter were collected during the growth period of the years 1999 and
      2000. The diversity of PE-rich Synechococcus spp. was examined using DGGE to
      analyze GC-clamped amplicons of a noncoding section of the 16S-23S intergenic
      spacer in the ribosomal operon. In both years, genotypes represented by three
      closely related PE-rich Synechococcus strains of our culture collection dominated
      the population, while other isolates were traced sporadically or were not
      detected in their original habitat by this method. For TNAs, primer-probe
      combinations for two taxonomic levels were used, one to quantify genomes of all
      known Synechococcus-type cyanobacteria in the APP of Lake Constance and one to
      enumerate genomes of a single ecotype represented by the PE-rich isolate
      Synechococcus sp. strain BO 8807. During the growth period, genome numbers of
      known Synechococcus spp. varied by 2 orders of magnitude (2.9 x 10(3) to 3.1 x
      10(5) genomes per ml). The ecotype Synechococcus sp. strain BO 8807 was detected
      in every sample at concentrations between 1.6 x 10(1) and 1.3 x 10(4) genomes per
      ml, contributing 0.02 to 5.7% of the quantified cyanobacterial picoplankton.
      Although the quantitative approach taken in this study has disclosed several
      shortcomings in the sampling and detection methods, this study demonstrated for
      the first time the extensive internal dynamics that lie beneath the seemingly
      arbitrary variations of a population of microbial photoautotrophs in the pelagic
      habitat.

PMID- 12200305
TI  - Evidence for natural horizontal transfer of the pcpB gene in the evolution of
      polychlorophenol-degrading sphingomonads.
AB  - The chlorophenol degradation pathway in Sphingobium chlorophenolicum is initiated
      by the pcpB gene product, pentachlorophenol-4-monooxygenase. The distribution of
      the gene was studied in a phylogenetically diverse group of polychlorophenol
      degrading bacteria isolated from contaminated groundwater in Karkola, Finland.
      All the sphingomonads isolated were shown to share pcpB gene homologs with 98.9
      to 100% sequence identity. The gene product was expressed when the strains were
      induced by 2,3,4,6-tetrachlorophenol. A comparative analysis of the 16S rDNA and
      pcpB gene trees suggested that a recent horizontal transfer of the pcpB gene was
      involved in the evolution of the catabolic pathway in the Karkola sphingomonads.
      The full-length Karkola pcpB gene allele had approximately 70% identity with the
      three pcpB genes previously sequenced from sphingomonads. It was very closely
      related to the environmental clones obtained from chlorophenol-enriched soil
      samples (M. Beaulieu, V. Becaert, L. Deschenes, and R. Villemur, Microbiol. Ecol.
      40:345-355, 2000). The gene was not present in polychlorophenol-degrading
      nonsphingomonads isolated from the Karkola source.

PMID- 12200306
TI  - Rhamnolipid stimulates uptake of hydrophobic compounds by Pseudomonas aeruginosa.
AB  - The biodegradation of hexadecane by five biosurfactant-producing bacterial
      strains (Pseudomonas aeruginosa UG2, Acinetobacter calcoaceticus RAG1,
      Rhodococcus erythropolis DSM 43066, R. erythropolis ATCC 19558, and strain
      BCG112) was determined in the presence and absence of exogenously added
      biosurfactants. The degradation of hexadecane by P. aeruginosa was stimulated
      only by the rhamnolipid biosurfactant produced by the same organism. This
      rhamnolipid did not stimulate the biodegradation of hexadecane by the four other
      strains to the same extent, nor was degradation of hexadecane by these strains
      stimulated by addition of their own biosurfactants. This suggests that P.
      aeruginosa has a mode of hexadecane uptake different from those of the other
      organisms. Rhamnolipid also enhanced the rate of epoxidation of the aliphatic
      hydrocarbon alpha,omega-tetradecadiene by a cell suspension of P. aeruginosa.
      Furthermore, the uptake of the hydrophobic probe 1-naphthylphenylamine by cells
      of P. aeruginosa was enhanced by rhamnolipid, as indicated by stopped-flow
      fluorescence experiments. Rhamnolipid did not stimulate the uptake rate of this
      probe in de-energized cells. These results indicate that an energy-dependent
      system is present in P. aeruginosa strain UG2 that mediates fast uptake of
      hydrophobic compounds in the presence of rhamnolipid.

PMID- 12200307
TI  - Lipopeptide production in Pseudomonas sp. strain DSS73 is regulated by components
      of sugar beet seed exudate via the Gac two-component regulatory system.
AB  - Pseudomonas sp. strain DSS73 isolated from the sugar beet rhizosphere produces
      the cyclic lipopeptide amphisin, which inhibits the growth of plant-pathogenic
      fungi. By Tn5::luxAB mutagenesis, we obtained two nonproducing mutant strains,
      DSS73-15C2 and DSS73-12H8. The gene interrupted by the transposon in strain DSS73
      15C2 (amsY) encoded a protein with homology to peptide synthetases that was
      designated amphisin synthetase. DSS73-12H8 carried the transposon in a regulatory
      gene encoding a protein with homology to the sensor kinase GacS. Growth of strain
      DSS73-15C2 (amsY) was impaired during the transition to stationary phase in a
      minimal medium amended with an exudate of sugar beet seeds. This growth phenotype
      could be complemented by purified amphisin. Seed exudate further induced
      expression of bioluminescence from the amsY::luxAB reporter during the transition
      to stationary phase. This agreed with an increase in amphisin production by the
      DSS73 wild-type strain during early stationary phase. Amphisin synthesis in DSS73
      was strictly dependent on GacS, and even induction by seed exudate depended on a
      functional gacS locus. Hence, a signal triggering the GacS/GacA two-component
      system appeared to be present in the seed exudate.

PMID- 12200308
TI  - Construction of yeast strains with high cell surface lipase activity by using
      novel display systems based on the Flo1p flocculation functional domain.
AB  - We constructed a novel cell-surface display system, using as a new type of cell
      wall anchor 3,297 or 4,341 bp of the 3' region of the FLO1 gene (FS or FL gene,
      respectively), which encodes the flocculation functional domain of Flo1p. In this
      system, the N terminus of the target protein was fused to the FS or FL protein
      and the fusion proteins were expressed under the control of the inducible
      promoter UPR-ICL (5' upstream region of the isocitrate lyase of Candida
      tropicalis). Using this new system, recombinant lipase with a pro sequence from
      Rhizopus oryzae (rProROL), which has its active site near the C terminus, was
      displayed on the cell surface. Cell-surface display of the FSProROL and FLProROL
      fusion proteins was confirmed by immunofluorescence microscopy and
      immunoblotting. Lipase activity reached 145 IU/liter (61.3 IU/g [dry cell
      weight]) on the surface of the yeast cells, which successfully catalyzed the
      methanolysis reaction. Using these whole-cell biocatalysts, methylesters
      synthesized from triglyceride and methanol reached 78.3% after 72 h of reaction.
      To our knowledge, this is the first example of cell-surface display of lipase
      with high activity. Interestingly, the yeast cells displaying the FLProROL
      protein showed strong flocculation, even though the glycosylphosphatidylinositol
      anchor attachment signal and cell-membrane-anchoring region of Flo1p had been
      deleted from this gene. The cell-surface display system based on FL thus endows
      the yeast strain with both novel enzyme display and strong flocculation ability.

PMID- 12200309
TI  - Environmental factors influencing human viral pathogens and their potential
      indicator organisms in the blue mussel, Mytilus edulis: the first Scandinavian
      report.
AB  - This study was carried out in order to investigate human enteric virus
      contaminants in mussels from three sites on the west coast of Sweden,
      representing a gradient of anthropogenic influence. Mussels were sampled monthly
      during the period from February 2000 to July 2001 and analyzed for adeno-, entero
      , Norwalk-like, and hepatitis A viruses as well as the potential viral indicator
      organisms somatic coliphages, F-specific RNA bacteriophages, bacteriophages
      infecting Bacteroides fragilis, and Escherichia coli. The influence of
      environmental factors such as water temperature, salinity, and land runoff on the
      occurrence of these microbes was also included in this study. Enteric viruses
      were found in 50 to 60% of the mussel samples, and there were no pronounced
      differences between the samples from the three sites. E. coli counts exceeded the
      limit for category A for shellfish sanitary safety in 40% of the samples from the
      sites situated in fjords. However, at the site in the outer archipelago, this
      limit was exceeded only once, in March 2001, when extremely high levels of
      atypical indole-negative strains of E. coli were registered at all three sites.
      The environmental factors influenced the occurrence of viruses and phages
      differently, and therefore, it was hard to find a coexistence between them. This
      study shows that, for risk assessment, separate modeling should be done for every
      specific area, with special emphasis on environmental factors such as temperature
      and land runoff. The present standard for human fecal contamination, E. coli,
      seems to be an acceptable indicator of only local sanitary contamination; it is
      not a reliable indicator of viral contaminants in mussels. To protect consumers
      and get verification of "clean" mussels, it seems necessary to analyze for
      viruses as well. The use of a molecular index of the human contamination of
      Swedish shellfish underscores the need for reference laboratories with high
      technology facilities.

PMID- 12200310
TI  - Fumarate-mediated inhibition of erythrose reductase, a key enzyme for erythritol
      production by Torula corallina.
AB  - Torula corallina, a strain presently being used for the industrial production of
      erythritol, has the highest erythritol yield ever reported for an erythritol
      producing microorganism. The increased production of erythritol by Torula
      corallina with trace elements such as Cu(2+) has been thoroughly reported, but
      the mechanism by which Cu(2+) increases the production of erythritol has not been
      studied. This study demonstrated that supplemental Cu(2+) enhanced the production
      of erythritol, while it significantly decreased the production of a major by
      product that accumulates during erythritol fermentation, which was identified as
      fumarate by instrumental analyses. Erythrose reductase, a key enzyme that
      converts erythrose to erythritol in T. corallina, was purified to homogeneity by
      chromatographic methods, including ion-exchange and affinity chromatography. In
      vitro, purified erythrose reductase was significantly inhibited noncompetitively
      by increasing the fumarate concentration. In contrast, the enzyme activity
      remained almost constant regardless of Cu(2+) concentration. This suggests that
      supplemental Cu(2+) reduced the production of fumarate, a strong inhibitor of
      erythrose reductase, which led to less inhibition of erythrose reductase and a
      high yield of erythritol. This is the first report that suggests catabolite
      repression by a tricarboxylic acid cycle intermediate in T. corallina.

PMID- 12200311
TI  - The bacterivorous soil flagellate Heteromita globosa reduces bacterial clogging
      under denitrifying conditions in sand-filled aquifer columns.
AB  - An exopolymer (slime)-producing soil bacterium Pseudomonas sp. (strain PS+)
      rapidly clogged sand-filled columns supplied with air-saturated artificial
      groundwater containing glucose (500 mg liter(-1)) as a sole carbon source and
      nitrate (300 mg liter(-1)) as an alternative electron acceptor. After 80 days of
      operation under denitrifying conditions, the effective porosity and saturated
      hydraulic conductivity (permeability) of sand in these columns had fallen by 2.5-
      and 26-fold, respectively. Bacterial biofilms appeared to induce clogging by
      occluding pore spaces with secreted exopolymer, although there may also have been
      a contribution from biogas generated during denitrification. The bacterivorous
      soil flagellate Heteromita globosa minimized reductions in effective porosity
      (1.6-fold) and permeability (13-fold), presumably due to grazing control of
      biofilms. Grazing may have limited growth of bacterial biomass and hence the rate
      of exopolymer and biogas secretion into pore spaces. Evidence for reduction in
      biogas production is suggested by increased nitrite efflux from columns
      containing flagellates, without a concomitant increase in nitrate consumption.
      There was no evidence that flagellates could improve flow conditions if added
      once clogging had occurred (60 days). Presumably, bacterial biofilms and their
      secretions were well established at that time. Nevertheless, this study provides
      evidence that bacterivorous flagellates may play a positive role in maintaining
      permeability in aquifers undergoing remediation treatments.

PMID- 12200312
TI  - Enzymatic properties and intracellular localization of the novel Trichoderma
      reesei beta-glucosidase BGLII (cel1A).
AB  - This paper describes the characterization of an intracellular beta-glucosidase
      enzyme BGLII (Cel1a) and its gene (bgl2) from the cellulolytic fungus Trichoderma
      reesei (Hypocrea jecorina). The expression pattern of bgl2 is similar to that of
      other cellulase genes known from this fungus, and the gene would appear to be
      under the control of carbon catabolite repression mediated by the cre1 gene. The
      BGLII protein was produced in Escherichia coli, and its enzymatic properties were
      analyzed. It was shown to be a specific beta-glucosidase, having no beta
      galactosidase side activity. It hydrolyzed both cellotriose and cellotetraose.
      BGLII exhibited transglycosylation activity, producing mainly cellotriose from
      cellobiose and sophorose and cellobiose from glucose. Antibodies raised against
      BGLII showed the presence of the enzyme in T. reesei cell lysates but not in the
      culture supernatant. Activity measurements and Western blot analysis of T. reesei
      strains expressing bgl2 from a constitutive promoter further confirmed the
      intracellular localization of this beta-glucosidase.

PMID- 12200313
TI  - Unveiling the organisms behind novel eukaryotic ribosomal DNA sequences from the
      ocean.
AB  - Despite the fact that the smallest eukaryotes (cells less than 5 micro m in
      diameter) play key roles in marine food webs, particularly in open oligotrophic
      areas, the study of their in situ diversity started just one year ago. Perhaps
      the most remarkable finding of the most recent studies has been the discovery of
      completely new phylogenetic lineages, such as novel clades belonging to the
      stramenopile and alveolate phyla. The two new groups account for a significant
      fraction of clones in genetic libraries from North Atlantic, equatorial Pacific,
      Antarctic, and Mediterranean Sea waters. However, the identities and ecological
      relevance of these organisms remain unknown. Here we investigate the phylogenetic
      relationships, morphology, in situ abundance, and ecological role of novel
      stramenopiles. They form at least eight independent clades within the
      stramenopile basal branches, indicating a large phylogenetic diversity within the
      group. Two lineages were visualized and enumerated in field samples and
      enrichments by fluorescent in situ hybridization using specific rRNA-targeted
      oligonucleotide probes. The targeted organisms were 2- to 3- micro m-diameter,
      round-shaped, nonpigmented flagellates. Further, they were found to be
      bacterivorous. One lineage accounted for up to 46% (average during an annual
      cycle, 19%) of heterotrophic flagellates in a coastal environment, providing
      evidence that novel stramenopiles are important and unrecognized components of
      the total stock of bacterial grazers.

PMID- 12200315
TI  - Identification and isolation of two ascomycete fungi from spores of the
      arbuscular mycorrhizal fungus Scutellospora castanea.
AB  - Two filamentous fungi with different phenotypes were isolated from crushed
      healthy spores or perforated dead spores of the arbuscular mycorrhizal fungus
      (AMF) Scutellospora castanea. Based on comparative sequence analysis of 5.8S
      ribosomal DNA and internal transcribed spacer fragments, one isolate, obtained
      from perforated dead spores only, was assigned to the genus Nectria, and the
      second, obtained from both healthy and dead spores, was assigned to
      Leptosphaeria, a genus that also contains pathogens of plants in the
      Brassicaceae. PCR and randomly amplified polymorphic DNA-PCR analyses, however,
      did not indicate similarities between pathogens and the isolate. The presence of
      the two isolates in both healthy spores and perforated dead spores of S. castanea
      was finally confirmed by transmission electron microscopy by using distinctive
      characteristics of the isolates and S. castanea. The role of this fungus in S.
      castanea spores remains unclear, but the results serve as a strong warning that
      sequences obtained from apparently healthy AMF spores cannot be presumed to be of
      glomalean origin and that this could present problems for studies on AMF genes.

PMID- 12200314
TI  - Rickettsia monacensis sp. nov., a spotted fever group Rickettsia, from ticks
      (Ixodes ricinus) collected in a European city park.
AB  - We describe the isolation and characterization of Rickettsia monacensis sp. nov.
      (type strain, IrR/Munich(T)) from an Ixodes ricinus tick collected in a city
      park, the English Garden in Munich, Germany. Rickettsiae were propagated in vitro
      with Ixodes scapularis cell line ISE6. BLAST analysis of the 16S rRNA, the
      citrate synthase, and the partial 190-kDa rickettsial outer membrane protein A
      (rOmpA) gene sequences demonstrated that the isolate was a spotted fever group
      (SFG) rickettsia closely related to several yet-to-be-cultivated rickettsiae
      associated with I. ricinus. Phylogenetic analysis of partial rompA sequences
      demonstrated that the isolate was genotypically different from other validated
      species of SFG rickettsiae. R. monacensis also replicated in cell lines derived
      from the ticks I. ricinus (IRE11) and Dermacentor andersoni (DAE100) and in the
      mammalian cell lines L-929 and Vero, causing cell lysis. Transmission electron
      microscopy of infected ISE6 and Vero cells showed rickettsiae within the
      cytoplasm, pseudopodia, nuclei, and vacuoles. Hamsters inoculated with R.
      monacensis had immunoglobulin G antibody titers as high as 1:16,384, as
      determined by indirect immunofluorescence assay. Western blot analyses
      demonstrated that the hamster sera cross-reacted with peptides from other
      phylogenetically distinct rickettsiae, including rOmpA. R. monacensis induced
      actin tails in both tick and mammalian cells similar to those reported for R.
      rickettsii. R. monacensis joins a growing list of SFG rickettsiae that colonize
      ticks but whose infectivity and pathogenicity for vertebrates are unknown.

PMID- 12200316
TI  - Isolation and characterization of differentially expressed genes in the mycelium
      and fruit body of Tuber borchii.
AB  - The transition from vegetative mycelium to fruit body in truffles requires
      differentiation processes which lead to edible fruit bodies (ascomata) consisting
      of different cell and tissue types. The identification of genes differentially
      expressed during these developmental processes can contribute greatly to a better
      understanding of truffle morphogenesis. A cDNA library was constructed from
      vegetative mycelium RNAs of the white truffle Tuber borchii, and 214 cDNAs were
      sequenced. Up to 58% of the expressed sequence tags corresponded to known genes.
      The majority of the identified sequences represented housekeeping proteins, i.e.,
      proteins involved in gene or protein expression, cell wall formation, primary and
      secondary metabolism, and signaling pathways. We screened 171 arrayed cDNAs by
      using cDNA probes constructed from mRNAs of vegetative mycelium and ascomata to
      identify fruit body-regulated genes. Comparisons of signals from vegetative
      mycelium and fruit bodies bearing 15 or 70% mature spores revealed significant
      differences in the expression levels for up to 33% of the investigated genes. The
      expression levels for six highly regulated genes were confirmed by RNA blot
      analyses. The expression of glutamine synthetase, 5-aminolevulinic acid
      synthetase, isocitrate lyase, thioredoxin, glucan 1,3-beta-glucosidase, and UDP
      glucose:sterol glucosyl transferase was highly up-regulated, suggesting that
      amino acid biosynthesis, the glyoxylate cycle pathway, and cell wall synthesis
      are strikingly altered during morphogenesis.

PMID- 12200317
TI  - Interaction of gene-cloned and insect cell-expressed aminopeptidase N of
      Spodoptera litura with insecticidal crystal protein Cry1C.
AB  - Insecticidal toxins produced by Bacillus thuringiensis interact with specific
      receptors located in the midguts of susceptible larvae, and the interaction is
      followed by a series of biochemical events that lead to the death of the insect.
      In order to elucidate the mechanism of action of B. thuringiensis toxins,
      receptor protein-encoding genes from many insect species have been cloned and
      characterized. In this paper we report the cloning, expression, and
      characterization of Cry toxin-interacting aminopeptidase N (APN) isolated from
      the midgut of a polyphagous pest, Spodoptera litura. The S. litura APN cDNA was
      expressed in the Sf21 insect cell line by using a baculovirus expression system.
      Immunofluorescence staining of the cells revealed that the expressed APN was
      located at the surface of Sf21 cells. Treatment of Sf21 cells expressing S.
      litura APN with phosphatidylinositol-specific phospholipase C demonstrated that
      the APN was anchored in the membrane by a glycosylphosphatidylinositol moiety.
      Interaction of the expressed receptor with different Cry toxins was examined by
      immunofluorescence toxin binding studies and ligand blot and immunoprecipitation
      analyses. By these experiments we showed that the bioactive toxin, Cry1C, binds
      to the recombinant APN, while the nonbioactive toxin, Cry1Ac, showed no
      interaction.

PMID- 12200318
TI  - Microscopic examination of distribution and phenotypic properties of
      phylogenetically diverse Chloroflexaceae-related bacteria in hot spring microbial
      mats.
AB  - We investigated the diversity, distribution, and phenotypes of uncultivated
      Chloroflexaceae-related bacteria in photosynthetic microbial mats of an alkaline
      hot spring (Mushroom Spring, Yellowstone National Park). By applying a directed
      PCR approach, molecular cloning, and sequence analysis of 16S rRNA genes, an
      unexpectedly large phylogenetic diversity among these bacteria was detected.
      Oligonucleotide probes were designed to target 16S rRNAs from organisms
      affiliated with the genus Chloroflexus or with the type C cluster, a group of
      previously discovered Chloroflexaceae relatives of this mat community. The
      application of peroxidase-labeled probes in conjunction with tyramide signal
      amplification enabled the identification of these organisms within the microbial
      mats by fluorescence in situ hybridization (FISH) and the investigation of their
      morphology, abundance, and small-scale distribution. FISH was combined with
      oxygen microelectrode measurements, microscope spectrometry, and
      microautoradiography to examine their microenvironment, pigmentation, and carbon
      source usage. Abundant type C-related, filamentous bacteria were found to
      flourish within the cyanobacterium-dominated, highly oxygenated top layers and to
      predominate numerically in deeper orange-colored zones of the investigated
      microbial mats, correlating with the distribution of bacteriochlorophyll a.
      Chloroflexus sp. filaments were rare at 60 degrees C but were more abundant at 70
      degrees C, where they were confined to the upper millimeter of the mat. Both type
      C organisms and Chloroflexus spp. were observed to assimilate radiolabeled
      acetate under in situ conditions.

PMID- 12200319
TI  - Construction and characterization of a proU-gfp transcriptional fusion that
      measures water availability in a microbial habitat.
AB  - We constructed and characterized a transcriptional fusion that measures the
      availability of water to a bacterial cell. This fusion between the proU promoter
      from Escherichia coli and the reporter gene gfp was introduced into strains of E.
      coli, Pantoea agglomerans, and Pseudomonas syringae. The proU-gfp fusion in these
      bacterial biosensor strains responded in a quantitative manner to water
      deprivation caused by the presence of NaCl, Na(2)SO(4), KCl, or polyethylene
      glycol (molecular weight, 8000). The fusion was induced to a detectable level by
      NaCl concentrations of as low as 10 mM in all three bacterial species. Water
      deprivation induced proU-gfp expression in both planktonic and surface-associated
      cells; however, it induced a higher level of expression in the surface-associated
      cells. Following the introduction of P. agglomerans biosensor cells onto bean
      leaves, the cells detected a significant decrease in water availability within
      only 5 min. After 30 min, the populations were exposed, on average, to a water
      potential equivalent to that imposed by approximately 55 mM NaCl. These results
      demonstrate the effectiveness of a proU-gfp-based biosensor for evaluating water
      availability on leaves. Furthermore, the inducibility of proU-gfp in multiple
      bacterial species illustrates the potential for tailoring proU-gfp-based
      biosensors to specific habitats.

PMID- 12200320
TI  - Isolation of tellurite- and selenite-resistant bacteria from hydrothermal vents
      of the Juan de Fuca Ridge in the Pacific Ocean.
AB  - Deep-ocean hydrothermal-vent environments are rich in heavy metals and metalloids
      and present excellent sites for the isolation of metal-resistant microorganisms.
      Both metalloid-oxide-resistant and metalloid-oxide-reducing bacteria were found.
      Tellurite- and selenite-reducing strains were isolated in high numbers from ocean
      water near hydrothermal vents, bacterial films, and sulfide-rich rocks. Growth of
      these isolates in media containing K(2)TeO(3) or Na(2)SeO(3) resulted in the
      accumulation of metallic tellurium or selenium. The MIC of K(2)TeO(3) ranged from
      1,500 to greater than 2,500 micro g/ml, and the MIC of Na(2)SeO(3) ranged from
      6,000 to greater than 7,000 micro g/ml for 10 strains. Phylogenetic analysis of 4
      of these 10 strains revealed that they form a branch closely related to members
      of the genus Pseudoalteromonas, within the gamma-3 subclass of the
      Proteobacteria. All 10 strains were found to be salt tolerant, pH tolerant, and
      thermotolerant. The metalloid resistance and morphological, physiological, and
      phylogenetic characteristics of newly isolated strains are described.

PMID- 12200321
TI  - Aquatic insects as a vector for Mycobacterium ulcerans.
AB  - Mycobacterium ulcerans is an emerging environmental pathogen which causes chronic
      skin ulcers (i.e., Buruli ulcer) in otherwise healthy humans living in tropical
      countries, particularly those in Africa. In spite of epidemiological and PCR data
      linking M. ulcerans to water, the mode of transmission of this organism remains
      elusive. To determine the role of aquatic insects in the transmission of M.
      ulcerans, we have set up an experimental model with aquariums that mimic aquatic
      microenvironments. We report that M. ulcerans may be transmitted to laboratory
      mice by the bite of aquatic bugs (Naucoridae) that are infected with this
      organism. In addition, M. ulcerans appears to be localized exclusively within
      salivary glands of these insects, where it can both survive and multiply without
      causing any observable damage in the insect tissues. Subsequently, we isolated M.
      ulcerans from wild aquatic insects collected from a zone in the Daloa region of
      Ivory Coast where Buruli ulcer is endemic. Taken together, these results point to
      aquatic insects as a possible vector of M. ulcerans.

PMID- 12200322
TI  - Abundance and phylogenetic affiliation of iron reducers in activated sludge as
      assessed by fluorescence in situ hybridization and microautoradiography.
AB  - Microautoradiography (MAR) was used to enumerate acetate-consuming bacteria under
      Fe(III)-reducing conditions in activated sludge. This population is believed to
      consist of dissimilatory iron-reducing bacteria, because the applied incubation
      conditions and the use of specific inhibitors excluded consumption of
      radiolabeled acetate by other physiological groups such as sulfate reducers. By
      use of this approach, dissimilatory iron reducers were found in a concentration
      of 1.1 x 10(8) cells per ml, corresponding to approximately 3% of the total cell
      count as determined by DAPI (4',6'-diamino-2-phenylindoledihydrochloride
      dilactate) staining. The MAR enumeration method was compared to the traditional
      most-probable-number (MPN) method (FeOOH-MPN) and a modified MPN method, which
      contains Ferrozine directly within the MPN dilutions to determine the production
      of small amounts of ferrous iron (Ferrozine-MPN). The Ferrozine-MPN method
      yielded values 6 to 10 times higher than those obtained by the FeOOH-MPN method.
      Nevertheless, the MAR approach yielded counts that were 100 to 1,000 times higher
      than those obtained by the Ferrozine-MPN method. Specific in situ Fe(III)
      reduction rates per cell (enumerated by the MAR method) were calculated and found
      to be comparable to the respective rates for pure cultures of dissimilatory iron
      reducing bacteria, suggesting that the new MAR method is most reliable. A
      combination of MAR and fluorescence in situ hybridization was used for
      phylogenetic characterization of the putative iron-reducing bacteria. All
      activated-sludge cells able to consume acetate under iron-reducing conditions
      were targeted by the bacterial oligonucleotide probe EUB338. Around 20% were
      identified as gamma Proteobacteria, and 10% were assigned to the delta subclass
      of Proteobacteria.

PMID- 12200323
TI  - Endosymbiotic bacteria in the esophageal organ of glossiphoniid leeches.
AB  - We characterized the intracellular symbiotic bacteria of the hematophagous
      glossiphoniid leeches Placobdelloides siamensis and a Parabdella sp. These
      leeches have a specialized structure called an "esophageal organ," the cells of
      which harbor bacterial symbionts. From the esophageal organ of each species, a
      1.5-kb eubacterial 16S rRNA gene segment was amplified by PCR, cloned, and
      sequenced. Diagnostic PCR detected the symbiont in the esophageal organ and
      intestine. Phylogenetic analysis of the 16S rRNA gene(s) demonstrated that the
      symbionts from the leeches formed a monophyletic group in a well-defined clade
      containing endosymbiotic bacteria of plant sap-feeding insects in the gamma
      subdivision of the Proteobacteria. The nucleotide compositions of the 16S rRNA
      gene from the leech symbionts were highly AT biased (53.7%).

PMID- 12200324
TI  - Effect of Weissella confusa strain PL9001 on the adherence and growth of
      Helicobacter pylori.
AB  - Viable and nonviable Weissella confusa strain PL9001 inhibited the binding of
      Helicobacter pylori to human gastric-cell line MKN-45 cells by more than 90%.
      Spent culture supernatant of PL9001 rapidly decreased the viability of H. pylori,
      rupturing cell walls. The results suggest that PL9001 is a probiotic that can
      reduce the infectivity and persistence of H. pylori.

PMID- 12200325
TI  - Infection of mice with aerosolized Mycobacterium tuberculosis: use of a nose-only
      apparatus for delivery of low doses of inocula and design of an ultrasafe
      facility.
AB  - Aerosolized delivery of virulent or hypervirulent Mycobacterium tuberculosis
      requires careful consideration of methodology and safety. To maximize safety, we
      installed a nose-only aerosol apparatus that can reproducibly deliver a low dose
      (<100 CFU per mouse) of M. tuberculosis in a carefully designed biohazard
      facility.

PMID- 12200326
TI  - Potential for misidentification of a spore-forming Paenibacillus polymyxa isolate
      as an endophyte by using culture-based methods.
AB  - While Paenibacillus polymyxa strain Pw-2 has been identified as an endophyte of
      lodgepole pine (M. Shishido, B. M. Loeb, and C. P. Chanway, Can. J. Microbiol.
      41:707-713, 1995), P. polymyxa strain L6 has not, a distinction that could be
      explained by the differential abilities of these isolates to form spores, rather
      than the differential abilities to colonize the interior tissues of lodgepole
      pine. Chemical disinfection was used to destroy bacteria on the root exterior,
      but bacterial endospores are known for their ability to withstand chemical
      disinfection, and strain Pw-2 was found to produce 300 to 11,000 times more
      germinating endospores than strain L6 under the experimental conditions used by
      Shishido et al. (Can. J. Microbiol. 41:707-713, 1995). Attempts to identify
      strain Pw-2 within lodgepole pine root tissues by using confocal microscopy
      techniques failed. We discuss the possibility that spore-forming bacteria can be
      mistakenly identified as endophytes when culture-based methods alone are used.

PMID- 12200327
TI  - Characterization of the lipopolysaccharides and capsules of Shewanella spp.
AB  - Electron microscopy, sodium dodecyl sulfate-polyacrylamide gel electrophoresis
      with silver staining and (1)H, (13)C, and (31)P-nuclear magnetic resonance (NMR)
      were used to detect and characterize the lipopolysaccharides (LPSs) of several
      Shewanella species. Many expressed only rough LPS; however, approximately one
      half produced smooth LPS (and/or capsular polysaccharides). Some LPSs were
      affected by growth temperature with increased chain length observed below 25
      degrees C. Maximum LPS heterogeneity was found at 15 to 20 degrees C. Thin
      sections of freeze-substituted cells revealed that Shewanella oneidensis, S.
      algae, S. frigidimarina, and Shewanella sp. strain MR-4 possessed either O-side
      chains or capsular fringes ranging from 20 to 130 nm in thickness depending on
      the species. NMR detected unusual sugars in S. putrefaciens CN32 and S. algae
      BrY(DL). It is possible that the ability of Shewanella to adhere to solid mineral
      phases (such as iron oxides) could be affected by the composition and length of
      surface polysaccharide polymers. These same polymers in S. algae may also
      contribute to this opportunistic pathogen's ability to promote infection.

PMID- 12200328
TI  - Gene disruption by homologous recombination in the Xylella fastidiosa citrus
      variegated chlorosis strain.
AB  - Mutagenesis by homologous recombination was evaluated in Xylella fastidiosa by
      using the bga gene, coding for beta-galactosidase, as a model. Integration of
      replicative plasmids by homologous recombination between the cloned truncated
      copy of bga and the endogenous gene was produced by one or two crossover events
      leading to beta-galactosidase mutants. A promoterless chloramphenicol
      acetyltransferase gene was used to monitor the expression of the target gene and
      to select a cvaB mutant.

PMID- 12200329
TI  - Quorum sensing and production of autoinducer-2 in Campylobacter spp., Escherichia
      coli O157:H7, and Salmonella enterica serovar Typhimurium in foods.
AB  - Autoinducer molecules are utilized by gram-negative and gram-positive bacteria to
      regulate density-dependent gene expression by a mechanism known as quorum
      sensing. PCR and DNA sequencing results showed that Campylobacter jejuni and
      Campylobacter coli possessed luxS, which is responsible for autoinducer-2 (AI-2)
      production. Using a Vibrio harveyi luminescence assay, the production of AI-2 was
      observed in milk, chicken broth, and brucella broth by C. coli, C. jejuni,
      Salmonella enterica serovar Typhimurium, and Escherichia coli O157:H7 under
      different conditions.

PMID- 12200330
TI  - Enzymatic degradation of chlorodiamino-s-triazine.
AB  - 2-Chloro-4,6-diamino-s-triazine (CAAT) is a metabolite of atrazine biodegradation
      in soils. Atrazine chlorohydrolase (AtzA) catalyzes the dechlorination of
      atrazine but is unreactive with CAAT. In this study, melamine deaminase (TriA),
      which is 98% identical to AtzA, catalyzed deamination of CAAT to produce 2-chloro
      4-amino-6-hydroxy-s-triazine (CAOT). CAOT underwent dechlorination via
      hydroxyatrazine ethylaminohydrolase (AtzB) to yield ammelide. This represents a
      newly discovered dechlorination reaction for AtzB. Ammelide was subsequently
      hydrolyzed by N-isopropylammelide isopropylaminohydrolase to produce cyanuric
      acid, a compound metabolized by a variety of soil bacteria.

PMID- 12200331
TI  - Escherichia coli O157 and non-O157 isolates are more susceptible to L-lactate
      than to D-lactate.
AB  - The antimicrobial effect of L-lactate was much greater than that of D-lactate
      over a range of concentrations for Escherichia coli O157 and non-O157 strains.
      Despite this, the intracellular pHs and membrane potentials of L-lactate- and D
      lactate-treated cells were similar, suggesting that these factors are not
      involved in the antimicrobial action of L-lactate.

PMID- 12200332
TI  - Comparison of models describing light dependence of N(2) fixation in
      heterocystous cyanobacteria.
AB  - The abilities of four models to describe nitrogenase light-response curves were
      compared, using the heterocystous cyanobacterium Nodularia spumigena and a
      cyanobacterial bloom from the Baltic Sea as examples. All tested models gave a
      good fit of the data, and the rectangular hyperbola model is recommended for
      fitting nitrogenase-light response curves. This model describes an enzymatic
      process, while the others are empirical. It was possible to convert the process
      parameters between the four models and compare N(2) fixation with photosynthesis.
      The physiological meanings of the process parameters are discussed and compared
      to those of photosynthesis.

PMID- 12200333
TI  - Enhanced degradation of an endocrine-disrupting chemical, butyl benzyl phthalate,
      by Fusarium oxysporum f. sp. pisi cutinase.
AB  - Compared to yeast esterase, fungal cutinase degraded butyl benzyl phthalate (BBP)
      far more efficiently; i.e., almost 60% of the BBP disappeared within 7.5 h. Also,
      the final chemical composition significantly depended on the enzyme used.
      Toxicity monitoring using bioluminescent bacteria showed that butyl methyl
      phthalate, a major product of degradation by esterase, was an oxidative toxic
      hazard.

PMID- 12200334
TI  - Cholesterol assimilation by lactic acid bacteria and bifidobacteria isolated from
      the human gut.
AB  - The objective of this study was to evaluate the effect of human gut-derived
      lactic acid bacteria and bifidobacteria on cholesterol levels in vitro.
      Continuous cultures inoculated with fecal material from healthy human volunteers
      with media supplemented with cholesterol and bile acids were used to enrich for
      potential cholesterol assimilators among the indigenous bacterial populations.
      Seven potential probiotics were found: Lactobacillus fermentum strains F53 and
      KC5b, Bifidobacterium infantis ATCC 15697, Streptococcus bovis ATCC 43143,
      Enterococcus durans DSM 20633, Enterococcus gallinarum, and Enterococcus
      faecalis. A comparative evaluation regarding the in vitro cholesterol reduction
      abilities of these strains along with commercial probiotics was undertaken. The
      degree of acid and bile tolerance of strains was also evaluated. The human
      isolate L. fermentum KC5b was able to maintain viability for 2 h at pH 2 and to
      grow in a medium with 4,000 mg of bile acids per liter. This strain was also able
      to remove a maximum of 14.8 mg of cholesterol per g (dry weight) of cells from
      the culture medium and therefore was regarded as a candidate probiotic.

PMID- 12200335
TI  - Diversity of Sinorhizobium meliloti from the Central Asian Alfalfa Gene Center.
AB  - Sinorhizobium meliloti was isolated from nodules and soil from western
      Tajikistan, a center of diversity of the host plants (Medicago, Melilotus, and
      Trigonella species). There was evidence of recombination, but significant
      disequilibrium, between and within the chromosome and megaplasmids. The most
      frequent alleles matched those in the published genome sequence.

PMID- 12200336
TI  - Tracing contamination and Escherichia coli diversity.

PMID- 12200337
TI  - The effect of viscosity on the perception of flavour.
AB  - A trained sensory panel assessed flavour and sweetness intensity in solutions
      containing varying concentrations of hydroxy propyl methylcellulose (HPMC), sugar
      and flavour volatile. The flavour and sweetness of the viscous solutions were
      rated using magnitude estimation with a controlled modulus. In addition, the
      concentration of volatile released on the breath was measured using MS Nose. For
      low concentrations of HPMC (<0.5 g/100 g), perceived flavour intensity remained
      the same; however, a steady decrease was noted at higher concentrations (>0.6
      g/100 g). The change in perceived intensity occurred at the point of random coil
      overlap (c(*)) for this hydrocolloid. The perceived sweetness of the solution
      showed a similar pattern with increasing HPMC concentration, although the
      inflection at c(*) was not so obvious. Despite the change in perceived flavour
      intensity, the actual concentration of volatile measured on the breath was not
      affected by the change in HPMC concentration. Low-order polynomial models were
      produced to describe perceived flavour intensity and sweetness in viscous
      solutions containing HPMC and potential explanations for the changes in
      perception are discussed.

PMID- 12200338
TI  - Sensitization and desensitization to allyl isothiocyanate (mustard oil) in the
      nasal cavity.
AB  - The aim of this study was to investigate the response, acute effects and time
      course of sensitization and desensitization to allyl isothiocyanate (mustard oil)
      nasal stimuli in healthy subjects. Sixty subjects participated in the experiment,
      which employed psychophysical (intensity ratings) and psychophysiological (skin
      conductance response) measurements. Nasal stimuli were delivered three times with
      different inter-stimulus intervals. The results showed that the psychophysical
      and psycho-physiological data were correlated and that the successive nasal
      stimuli after a short period of time (<2 min) produced increased intensity of
      irritation, whereas the stimuli delivered after >3 min produced a markedly
      decreased intensity of irritation. These findings are in agreement with those
      obtained with capsaicin, the most frequently used irritant molecule.

PMID- 12200339
TI  - Voltage- and calcium-activated currents in cultured olfactory receptor neurons of
      male Mamestra brassicae (Lepidoptera).
AB  - Insect olfactory receptor neurons (ORNs) grown in primary cultures were studied
      using the patch-clamp technique in both conventional and amphotericin B
      perforated whole-cell configurations under voltage-clamp conditions. After 10-24
      days in vitro, ORNs had a mean resting potential of -62 mV and an average input
      resistance of 3.2 GOmega. Five different voltage-dependent ionic currents were
      isolated: one Na(+), one Ca(2+) and three K(+) currents. The Na(+) current (35
      300 pA) activated between -50 and -30 mV and was sensitive to 1 microM
      tetrodotoxin (TTX). The sustained Ca(2+) current activated between -30 and -20
      mV, reached a maximum amplitude at 0 mV (-4.5 +/- 6.0 pA) that increased when
      Ba(2+) was added to the bath and was blocked by 1 mM Co(2+). Total outward
      currents were composed of three K(+) currents: a Ca(2+)-activated K(+) current
      activated between -40 and -30 mV and reached a maximum amplitude at +40 mV (605
      +/- 351 pA); a delayed-rectifier K(+) current activated between -30 and -10 mV,
      had a mean amplitude of 111 +/- 67 pA at +60 mV and was inhibited by 20 mM
      tetraethylammonium (TEA); and, finally, more than half of ORNs exhibited an A
      like current strongly dependent on the holding potential and inhibited by 5 mM 4
      aminopyridine (4-AP). Pheromone stimulation evoked inward current as measured by
      single channel recordings.

PMID- 12200340
TI  - Distortion of olfactory perception: diagnosis and treatment.
AB  - Clinically, olfaction can fail in any of three ways: (i) decreased sensitivity
      (hyposmia, anosmia) and two types of distortion (dysosmia); (ii) distorted
      quality of an odorant stimulation (troposmia); (iii) perceived odor when no
      odorant is present (phantosmia, hallucination). The distortions are usually much
      more upsetting to a person's quality of life than a simple loss. An ipsilatersal
      loss of olfactory sensitivity is often identified in the nostril with any type of
      olfactory distortion. The pathophysiology of a stimulated distortion (troposmia)
      is likely a decreased number of functioning olfactory primary neurons so that an
      incomplete characterization of the odorant is made. In phantosmia, two possible
      causations include an abnormal signal or inhibition from the primary olfactory
      neurons or peripheral olfactory or trigeminal signals that "trigger" a central
      process. The clinician's goal is to carefully define the problem (e.g. taste
      versus smell, real versus perceived, one versus two nostrils), to perform the
      appropriate examination and testing and to provide therapy if possible. Treatment
      includes assurance with no active therapy (because many of these will naturally
      resolve), topical medications, systemic medications, anesthesia to parts of the
      nose and, rarely, referral for surgical excision of olfactory neurons. Endoscopic
      transnasal operations have the advantage of treating phantosmia and sometimes
      allowing a return of olfactory ability after the operation.

PMID- 12200341
TI  - Anti-inflammatory and surgical therapy of olfactory disorders related to sino
      nasal disease.
AB  - Olfactory loss may be caused by mechanical obstruction or inflammation of the
      olfactory epithelium due to allergic/non-allergic rhinitis and chronic sinusitis
      with or without polyps. Treatment of olfactory loss related to sino-nasal disease
      is possible. Apart from surgical approaches and/or treatment with antibiotics,
      both systemic and topical steroids are effectively used in the therapy of
      olfactory loss related to sino-nasal disease. In most cases improvement of
      olfactory function appears to relate to the anti-inflammatory actions of the
      steroids used. While some details of therapeutic effect and dose regimen are not
      clear, systemic steroids are often helpful even in patients without nasal
      obstruction due to polyps or obvious inflammatory changes.

PMID- 12200342
TI  - Biopsies of human olfactory epithelium.
AB  - It has been shown that olfactory epithelium can be safely biopsied from the
      living, intact human being. Observations of the ultrastructure of this epithelium
      shows changes that can then be correlated with the etiology and degree of
      olfactory loss, allowing a greater understanding of both normal transduction and
      of the pathology of dysfunction. Examples of the common forms of olfactory
      dysfunction are presented and discussed. Additionally, the technique will allow
      additional immuno-histochemical and molecular study of the tissue, will increase
      the understanding of both normal and pathological function and should translate
      to new therapeutic regimens.

PMID- 12200343
TI  - Gustatory evoked cortical activity in humans studied by simultaneous EEG and MEG
      recording.
AB  - Evoked potentials are widely used in clinical medicine for objective evaluation
      of sensory disturbances. However, gustatory evoked potentials (GEPs) have not
      been extensively studied due to lack of agreement among investigators regarding
      the waveforms. In this study GEPs and gustatory magnetic fields (GEMfs) were
      simultaneously recorded from five subjects in response to 0.3 M NaCl in an
      attempt to establish GEP recording as an objective gustatometer. Each subject
      received a total of 240 stimulus presentations over six sessions. Three GEP
      components (P1, N1 and P2) were observed and correlated with their corresponding
      equivalent current dipoles (ECD1, ECD2 and ECD3, respectively). ECD1 was
      localized to area G in all subjects, P1 being the indicator of intact gustatory
      projection to area G. No significant GEP activity was detected during the time
      preceding P1, which suggests that there was no activity in cortical gyri other
      than that detected by magnetoencephalography. ECD2 and ECD3 were localized to
      various cortical structures, including the inferior insula and the superior
      temporal sulcus, indicating that N1 and P2 reflect higher order gustatory
      functions. The present results indicate that measurement of GEPs may be useful
      for objective evaluation of gustatory disturbance.

PMID- 12200344
TI  - Comparison of mechanical agitation and calcium shock methods for preparation of a
      membrane fraction enriched in olfactory cilia.
AB  - Calcium plays an important regulatory role in olfactory signal transduction. Many
      investigations into the regulation of the olfactory signaling pathway have been
      performed using fractions enriched in ciliary membranes from olfactory sensory
      neurons. The traditional method of preparing ciliary fractions uses high calcium
      concentrations, thought to dislodge cilia from the dendritic knobs of the
      olfactory neurons in the nasal epithelium. However, calcium, an important second
      messenger in the odorant signaling cascade, modulates the activity of many
      enzymatic reactions in this cascade. Pre-exposure of cilia to high calcium
      concentrations may modify these signaling events. Therefore, we sought to develop
      a method of isolating cilia-enriched membranes that avoids exposing the cilia to
      high calcium concentrations. Our method of isolation, referred to as the
      mechanical agitation method, involves mechanical disruption and sonication of the
      olfactory epithelium to dislodge the cilia. To evaluate this method of cilia
      preparation, basal adenylyl cyclase activity, as well as forskolin- and odorant
      activated adenylyl cyclase, were analyzed. Specific activity of adenylyl cyclase
      and protein yield were compared for the mechanical agitation and the high calcium
      preparations. Immunoblots were analyzed for the presence of transduction
      components enriched in olfactory cilia: adenylyl cyclase type III (ACIII),
      heterotrimeric G-protein subunit Galphaolf and the 1 C2 isoform of
      phosphodiesterase (PDE 1 C2). Based on these analyses, the ciliary fraction
      prepared by the mechanical agitation method appears to be very similar to that
      prepared by the high calcium method, with a higher yield.

PMID- 12200345
TI  - Characterization of cAMP degradation by phosphodiesterases in the accessory
      olfactory system.
AB  - To characterize the potential role of cAMP in pheromone transduction, we have
      examined the occurrence of cyclic nucleotide phosphodiesterases (PDEs) in the
      mouse vomeronasal organ (VNO). We show that the cAMP-specific isoforms PDE4A and
      PDE4D are found preferentially in the apical and basal layers, respectively, of
      the VNO neuroepithelium and in the rostral (PDE4A) and caudal (PDE4D) portions of
      the accessory olfactory bulb glomerular layer. Assays for cAMP hydrolysis showed
      that PDE activity in VNO homogenates was about half that measured in the cerebral
      cortex and olfactory epithelium, and the proportion of total activity inhibited
      by rolipram, a PDE4-specific inhibitor, was approximately 40%. Activity in the
      VNO was enhanced 60% by Ca(2+) and calmodulin (CaM), implicating the presence of
      Ca(2+)/CaM-dependent PDE1. Zaprinast, which is known to inhibit PDE1C isoforms,
      completely suppressed Ca(2+)/CaM-stimulated activity and, together, zaprinast and
      rolipram inhibited cAMP hydrolysis by approximately 70%. Our results suggest that
      PDE1 and PDE4 isoforms are the primary source of cAMP degradation in the VNO.

PMID- 12200346
TI  - Turbidity as a measure of salivary protein reactions with astringent substances.
AB  - Binding of tannins to proline-rich proteins has been proposed as an initial step
      in the development of astringent sensations. In beer and fruit juices, formation
      of tannin-protein complexes leads to the well-known effect of haze development or
      turbidity. Two experiments examined the development of turbidity in human saliva
      when mixed with tannins as a potential in vitro correlate of astringent
      sensations. In the first study, haze was measured in filtered human saliva mixed
      with a range of tannic acid concentrations known to produce supra-threshold
      psychophysical responses. The second study examined relationships among
      individual differences in haze development and the magnitude of astringency
      ratings. Mostly negative correlations were found, consistent with the notion that
      high levels of salivary proteins protect oral tissues from the drying effects of
      tannic acid.

PMID- 12200350
TI  - Natural killer cell receptors: new biology and insights into the graft-versus
      leukemia effect.
AB  - Natural killer (NK) cells have held great promise for the immunotherapy of cancer
      for more than 3 decades. However, to date only modest clinical success has been
      achieved manipulating the NK cell compartment in patients with malignant disease.
      Progress in the field of NK cell receptors has revolutionized our concept of how
      NK cells selectively recognize and lyse tumor and virally infected cells while
      sparing normal cells. Major families of cell surface receptors that inhibit and
      activate NK cells to lyse target cells have been characterized, including killer
      cell immunoglobulinlike receptors (KIRs), C-type lectins, and natural
      cytotoxicity receptors (NCRs). Further, identification of NK receptor ligands and
      their expression on normal and transformed cells completes the information needed
      to begin development of rational clinical approaches to manipulating
      receptor/ligand interactions for clinical benefit. Indeed, clinical data suggest
      that mismatch of NK receptors and ligands during allogeneic bone marrow
      transplantation may be used to prevent leukemia relapse. Here, we review how NK
      cell receptors control natural cytotoxicity and novel approaches to manipulating
      NK receptor-ligand interactions for the potential benefit of patients with
      cancer.

PMID- 12200351
TI  - CCL19 induces rapid dendritic extension of murine dendritic cells.
AB  - Dendritic cells (DCs) possess numerous dendrites that may be of great advantage
      to interaction with T cells. However, it has been poorly understood how the
      dendritic morphology of a DC is controlled. In the present study, using a murine
      spleen-derived DC line, we analyzed effects of CCR7 ligands, CCL19 and CCL21, on
      dendritic morphology. Mature DCs, but not immature DCs, showed vigorous migration
      to either CCL19 or CCL21. CCL19 also rapidly (within 30 minutes) induced marked
      extension of dendrites of mature DCs that was maintained at least for 24 hours.
      On the other hand, CCL21 failed to induce rapid dendritic extension, even though
      a modest dendritic extension of mature DCs, compared to that by CCL19, was
      induced 8 or 24 hours after treatment with CCL21. In addition, pretreatment with
      a high concentration of CCL21 significantly inhibited the rapid dendritic
      extension induced by CCL19. Thus, it is suggested that CCL19 and CCL21 exert
      agonistic and antagonistic influences on the initiation of dendritic extension of
      mature DCs. The CCL19-induced morphologic changes were completely blocked by
      Clostridium difficile toxin B that inhibits Rho guanosine triphosphatase proteins
      such as Rho, Rac, and Cdc42, but not by Y-27632, a specific inhibitor for Rho
      associated kinase. These findings suggest that Rac or Cdc42 (or both), but not
      Rho, are involved in the CCL19-induced dendritic extension of mature DCs.

PMID- 12200352
TI  - Racial and ethnic differences in survival of children with acute lymphoblastic
      leukemia.
AB  - Black children with acute lymphoblastic leukemia (ALL) have poor outcomes, but
      limited information is available for children from other racial and ethnic
      backgrounds, such as Hispanic and Asian. We undertook a retrospective cohort
      study of children with ALL treated on Children's Cancer Group therapeutic
      protocols to determine outcomes by racial and ethnic backgrounds of patients
      treated with contemporary risk-based therapy. In total, 8447 children (white, n =
      6703; Hispanic, n = 1071; black, n = 506; and Asian, n = 167) with newly
      diagnosed ALL between 1983 and 1995 were observed for a median of 6.5 years.
      Analysis of disease outcome was measured as overall survival (OS) and event-free
      survival (EFS) and was adjusted for known predictors of outcome including
      clinical features, disease biology, socioeconomic status, and treatment era (1983
      1989 vs 1989-1995). There was a statistically significant difference in survival
      by ethnicity (P <.001). Five-year EFS rates were: Asian, 75.1% +/- 3.5%; white,
      72.8% +/- 0.6%; Hispanic, 65.9% +/- 1.5%; and black, 61.5% +/- 2.2%. Multivariate
      analysis revealed that when compared with white children, black and Hispanic
      children had worse outcomes and Asian children had better outcomes after
      adjusting for known risk factors. The poorer outcomes among black children were
      most apparent among patients with standard-risk features (relative risk [RR],
      2.0; 95% confidence interval [CI], 1.6-2.5), whereas poorer outcomes in Hispanic
      children (RR, 1.4; 95% CI, 1.2-1.6) were most evident among patients with high
      risk features. Asian children had better outcomes than all racial and ethnic
      groups among high-risk patients, particularly in the recent era (5-year EFS,
      90.9% +/- 6.1%). Racial and ethnic differences in OS and EFS persist among
      children with ALL who receive contemporary risk-based therapy. Future studies
      should focus on reasons-perhaps compliance or pharmacogenetics-for those
      differences.

PMID- 12200353
TI  - A phase 2 study of imatinib in patients with relapsed or refractory Philadelphia
      chromosome-positive acute lymphoid leukemias.
AB  - The translocation (9;22) gives rise to the p190(Bcr-Abl) and p210(Bcr-Abl)
      tyrosine kinase proteins, considered sufficient for leukemic transformation.
      Philadelphia-positive (Ph(+)) acute leukemia patients failing to respond to
      initial induction therapy have a poor prognosis with few effective treatment
      options. Imatinib is an orally administered, potent inhibitor of the Bcr-Abl
      tyrosine kinase. We conducted a clinical trial in 56 patients with relapsed or
      refractory Ph(+) acute lymphoblastic leukemia (ALL; 48 patients) or chronic
      myelogenous leukemia in lymphoid blast crisis (LyBC; 8 patients). Imatinib was
      given once daily at 400 mg or 600 mg. Imatinib induced complete hematologic
      responses (CHRs) and complete marrow responses (marrow-CRs) in 29% of ALL
      patients (CHR, 19%; marrow-CR, 10%), which were sustained for at least 4 weeks in
      6% of patients. Median estimated time to progression and overall survival for ALL
      patients were 2.2 and 4.9 months, respectively. CHRs were reported for 3 (38%) of
      the patients with LyBC (one sustained CHR). Grade 3 or 4 treatment-related
      nonhematologic toxicity was reported for 9% of patients; none of the patients
      discontinued therapy because of nonhematologic adverse reactions. Grade 4
      neutropenia and thrombocytopenia occurred in 54% and 27% of patients,
      respectively. Imatinib therapy resulted in a clinically relevant hematologic
      response rate in relapsed or refractory Ph(+) acute lymphoid leukemia patients,
      but development of resistance and subsequent disease progression were rapid.
      Further studies are warranted to test the effects of imatinib in combination with
      other agents and to define the mechanisms of resistance to imatinib.

PMID- 12200354
TI  - Clinicobiological features and outcome of acute promyelocytic leukemia occurring
      as a second tumor: the GIMEMA experience.
AB  - We analyzed the clinicobiological features and treatment outcome of a series of
      acute promyelocytic leukemias (APLs) occurring as a second tumor (APL-st's, n =
      51) and compared these with a large group of de novo APL cases (n = 641), both
      observed by the Italian cooperative group GIMEMA. In the APL-st group, 37
      patients had received radiotherapy and/or chemotherapy for their primary
      malignancy (PM), while 14 had been treated by surgery alone. Compared with de
      novo APL patients, APL-st patients were characterized by a predominance of
      females (P <.003), higher median age (P <.05), and worse performance status (P
      <.005). The median time elapsed between PM and APL-st was 36 months, with a
      longer latency for patients treated with surgery alone. No significant
      differences were found with regard to karyotypic lesions or type of promyelocytic
      leukemia/retinoic acid receptor alpha (PML/RARalpha) fusion in the 2 cohorts. A
      high prevalence of PMs of the reproductive system was observed among the female
      APL-st population (24 [71%] of 34 patients in this group had suffered from
      breast, uterine, or ovarian cancer). Thirty-one APL-st and 641 de novo APL
      patients received homogeneous APL therapy according to the all-trans retinoic
      acid (ATRA) and idarubicin regimen (the AIDA regimen). The complete remission
      (CR), 4-year event-free survival (EFS), and 4-year overall survival (OS) rates
      were 97% and 93%, 65% and 68%, and 85% and 78% in the APL-st and de novo APL
      groups, respectively. In spite of important clinical differences (older age and
      poorer performance status), the APL-st group responded as well as the de novo APL
      group to upfront ATRA plus chemotherapy, probably reflecting genetic similarity.

PMID- 12200355
TI  - Ursodeoxycholic acid for the prevention of hepatic complications in allogeneic
      stem cell transplantation.
AB  - The role of ursodeoxycholic acid (UDCA) in the prevention of hepatic
      complications after allogeneic stem cell transplantation was studied in a
      prospective randomized open-label multicenter trial. A total of 242 patients were
      allocated to receive (n = 123) or not to receive (n = 119) UDCA in the dose of 12
      mg/kg/d orally from the day preceding the conditioning until day 90 after
      transplantation. In the UDCA-treated group a significantly smaller proportion of
      patients developed a serum bilirubin level exceeding 50 microM (18 of 123 versus
      31 of 119, P =.04), and similarly a smaller proportion of patients exceeded the
      alanine aminotransferase level of 100 U/L. There was no difference in the
      incidence of veno-occlusive disease of the liver. Compared to the control group,
      in the UDCA-treated group there was a nonsignificant trend toward a lower overall
      incidence of acute graft-versus-host disease (GVHD) and a significantly lower
      incidence of grade III to IV acute GVHD (5 of 123 versus 17 of 119, P =.01),
      stage II to IV liver and intestinal GVHD, and stage III to IV skin GVHD. There
      was no difference in the incidence of chronic GVHD or in the relapse rate. Among
      the patients given UDCA, the survival at 1 year was significantly better, 71%
      versus 55% (P =.02), and the nonrelapse mortality rate was lower, 19% versus 34%
      (P =.01), than in the control group. There were significantly more deaths in GVHD
      in the control group. In conclusion, UDCA administration reduced hepatic problems
      and severe acute GVHD and improved survival. These results suggest a role for
      UDCA in the prevention of transplant-related complications in allogeneic
      transplantation.

PMID- 12200356
TI  - Stanford V regimen and concomitant HAART in 59 patients with Hodgkin disease and
      HIV infection.
AB  - A phase 2 prospective study was performed to evaluate the feasibility and
      activity of a short, dose-intensive chemotherapy regimen and radiotherapy (the
      Stanford V regimen) plus highly active antiretroviral therapy (HAART) and
      granulocyte colony-stimulating factor (G-CSF) support in patients with Hodgkin
      disease and HIV infection. Fifty-nine patients were enrolled. Stanford V was well
      tolerated and 69% of the patients completed treatment with no dose reduction or
      delayed chemotherapy administration. The most important dose-limiting side
      effects were bone marrow toxicity and neurotoxicity. Complete remission was
      achieved by 81% of the patients, and after a median follow-up of 17 months 33
      patients (56%) were alive and disease-free. The estimated 3-year overall survival
      (OS), disease-free survival (DFS), and freedom from progression (FFP) were 51%,
      68%, and 60%, respectively. Probability of FFP was significantly (P =.02) higher
      among patients with an International Prognostic Score (IPS) of 2 or lower than in
      those with an IPS higher than 2, and the percentages of FFP at 2 years in these
      groups were 83% and 41%, respectively. Similarly, the probability of OS was
      significantly (P =.0004) different in the 2 groups, and the percentages of OS at
      3 years were 76% and 33%, respectively. Our data confirm that the Stanford V
      regimen with concomitant HAART is feasible and active in an HIV setting. However,
      a more intensive approach should be considered in patients with high IPSs.

PMID- 12200357
TI  - Second malignancy after Hodgkin disease treated with radiation therapy with or
      without chemotherapy: long-term risks and risk factors.
AB  - The excess risk of second malignancy after Hodgkin disease is an increasing
      problem. In light of the long-term data, guidelines for follow-up of survivors of
      Hodgkin disease need to be redefined. In this study we attempt to analyze the
      long-term risks and temporal trends, identify patient- and treatment-related risk
      factors, and determine the prognosis of patients who develop a second malignancy
      after radiation treatment with or without chemotherapy for Hodgkin disease. Among
      1319 patients with clinical stage I-IV Hodgkin disease, 181 second malignancies
      and 18 third malignancies were observed. With a median follow-up of 12 years, the
      relative risk (RR) and absolute excess risk of second malignancy were 4.6 and
      89.3/10 000 person-years. The RR was significantly higher with combined
      chemotherapy and radiation therapy (6.1) than with radiation therapy alone (4.0,
      P =.015). The risk increased with increasing radiation field size (P =.03) in
      patients who received combined modality therapy, and with time after Hodgkin
      disease. After 15 and 20 years, there was a 2.3% and 4.0% excess risk of second
      malignancy per person per year. The 5-year survival after development of a second
      malignancy was 38.1%, with the worst prognosis seen after acute leukemia and lung
      cancer. The excess risk of second malignancy after Hodgkin disease continues to
      be increased after 15 to 20 years, and there does not appear to be a plateau. Our
      analysis suggests that the risk may be reduced with smaller radiation fields, as
      are used in current trials of abbreviated chemotherapy and limited-field
      radiation therapy.

PMID- 12200358
TI  - Bone marrow transplantation from HLA-identical siblings as treatment for
      myelodysplasia.
AB  - Allogeneic hematopoietic stem cell transplantation is the only curative therapy
      for myelodysplasia (MDS). To identify factors influencing transplantation
      outcome, we studied 452 recipients of HLA-identical sibling transplants for MDS
      from 1989 to 1997, reported to the International Bone Marrow Transplant Registry.
      Patients with treatment-related MDS or unclassified MDS were excluded. Median age
      was 38 years (range, 2-64 years). Sixty percent had refractory anemia with excess
      blasts (n = 136) or with excess blasts in transformation (n = 136). Conditioning
      regimens included total body irradiation in 199 (44%) cases. Marrow was T-cell
      depleted for 58 (13%) transplants. Cumulative incidences of neutrophil
      engraftment, grades II-IV acute graft-versus-host disease (GVHD), and chronic
      GVHD were 91% (95% confidence interval [CI], 88%-93%), 36% (95% CI, 31%-40%), and
      39% (95% CI, 33%-44%), respectively. Three-year transplantation-related mortality
      (TRM), relapse, disease-free survival, and overall survival rates were 37% (95%
      CI, 32%-42%), 23% (95% CI, 19%-27%), 40% (95% CI, 36%-45%), and 42% (95% CI, 37%
      47%), respectively. Multivariate analyses showed that young age and platelet
      counts higher than 100 x 10(9)/L at transplantation were associated with lower
      TRM and higher disease-free and overall survival rates. Relapse incidence was
      higher in patients with high percentages of blasts in the marrow at
      transplantation or presentation, with high International Prognostic Scoring
      System scores at diagnosis, and with T-cell-depleted transplants. These findings
      indicate that transplantation from an HLA-identical sibling offers the
      possibility of long-term, disease-free survival to patients with MDS. Best
      candidates are younger patients with a low percentage of blasts and preserved
      platelet counts.

PMID- 12200359
TI  - High incidence of human herpesvirus 6 infection with a high viral load in cord
      blood stem cell transplant recipients.
AB  - Human herpesvirus 6 (HHV-6) infection in recipients of cord blood stem cell
      transplants (CBSCTs) was estimated by semiquantitative and real-time quantitative
      polymerase chain reaction (PCR) and reverse-transcription PCR. Of the CBSCT
      recipients, 7 (70%) of 10 had active HHV-6 infection after transplantation, and
      all 7 were inferred from their age to have already had a primary infection.
      Because HHV-6 DNA is seldom detected in cord blood, these cases were considered
      likely to represent reactivation. In contrast, the 3 patients without HHV-6
      infection were all believed to be naive regarding HHV-6 primary infection because
      of their age and the results of PCR assays given before the transplantation
      procedure. The incidence of HHV-6 infection after transplantation was
      significantly higher (P <.05) than after bone marrow (BM) transplantation and
      peripheral blood stem cell (PBSC) transplantation, when recipients without
      primary HHV-6 infection prior to transplantation were excluded (CBSCT, 100%;
      BMT/PBSCT, 56.3%). Real-time PCR revealed a higher level of viral DNA in the
      peripheral blood mononuclear cells from CBSCT recipients than from BMT/PBSCT
      recipients or patients with exanthem subitum (P <.05). HHV-6 mRNA of the U79/80
      gene was also detected by reverse-transcription PCR in all analyzed patients with
      HHV-6 infection. Its detection was correlated with the emergence of viral DNA in
      the plasma and symptoms such as fever and rash. Thus, HHV-6 infection was more
      frequent and the viral load was higher in CBSCT recipients with prior primary
      infection.

PMID- 12200360
TI  - Development of virus vectors for gene therapy of beta chain hemoglobinopathies:
      flanking with a chromatin insulator reduces gamma-globin gene silencing in vivo.
AB  - We have previously described the development of oncoretrovirus vectors for human
      gamma-globin using a truncated beta-globin promoter, modified gamma-globin
      cassette, and alpha-globin enhancer. However, one of these vectors is genetically
      unstable, and both vectors exhibit variable expression patterns in cultured
      cells, common characteristics of oncoretrovirus vectors for globin genes. To
      address these problems, we identified and removed the vector sequences
      responsible for genetic instability and flanked the resultant vector with the
      chicken beta-globin HS4 chromatin insulator to protect expression from
      chromosomal position effects. After determining that flanking with the cHS4
      element allowed higher, more uniform levels of gamma-globin expression in MEL
      cell lines, we tested these vectors using a mouse bone marrow transduction and
      transplantation model. When present, the gamma-globin cassettes from the
      uninsulated vectors were expressed in only 2% to 5% of red blood cells (RBCs)
      long term, indicating they are highly sensitive to epigenetic silencing. In
      contrast, when present the gamma-globin cassette from the insulated vector was
      expressed in 49% +/- 20% of RBCs long term. RNase protection analysis indicated
      that the insulated gamma-globin cassette was expressed at 23% +/- 16% per copy of
      mouse alpha-globin in transduced RBCs. These results demonstrate that flanking a
      globin vector with the cHS4 insulator increases the likelihood of expression
      nearly 10-fold, which in turn allows for gamma-globin expression approaching the
      therapeutic range for sickle cell anemia and beta thalassemia.

PMID- 12200361
TI  - Graft-versus-leukemia effect after suicide-gene-mediated control of graft-versus
      host disease.
AB  - Clinical data indicate that after allogeneic hematopoietic stem cell
      transplantation (HSCT) for hematological malignancies, the graft-versus-leukemia
      (GVL) effect is in large part mediated by the graft-versus-host reaction (GVHR),
      which also often leads to graft-versus-host disease (GVHD). Controlling
      alloreactivity to prevent GVHD while retaining GVL poses a true dilemma for the
      successful treatment of such malignancies. We reasoned that suicide gene therapy,
      which kills dividing cells expressing the thymidine kinase (TK) "suicide" gene
      using time-controlled administration of ganciclovir (GCV), might solve this
      dilemma. We have previously shown that after infusion of allogeneic TK T cells
      along with HSCT to an irradiated recipient, an early and short GCV treatment
      efficiently prevents GVHD by selectively eliminating alloreactive T cells while
      sparing nonalloreactive T cells, which can then contribute to immune
      reconstitution. Nevertheless, it remained to be established that this therapeutic
      strategy retained the desired GVL effect. Hypothesizing that a contained GVHR
      would be essential, we evaluated the GVL effect using different protocols of GCV
      administration. We were able to show that when the GCV treatment is initiated at,
      or close to, the time of grafting, GVHD is controlled but GVL is lost. In
      contrast, when the onset of GCV administration is delayed until day 6, a potent
      GVL effect is retained while GVHD is still controlled. These data emphasize that,
      by a time-optimized scheduling of the administration of GCV, this TK/GCV strategy
      can be tuned to efficiently treat malignant hemopathies.

PMID- 12200362
TI  - Pharmacologically regulated in vivo selection in a large animal.
AB  - The inefficiency of gene transfer has greatly hindered gene therapy. In vivo
      selection may increase the frequency of genetically modified cells, thereby
      circumventing this critical limitation. Here we demonstrate regulated in vivo
      selection in a large animal. CD34(+) cells from 2 dogs were engineered to express
      a conditional derivative of the thrombopoietin receptor (F36Vmpl). Activation of
      the receptor through administration of a dimerizing drug, AP20187, produced
      reversible, drug-dependent rises in genetically modified red cells, white cells,
      and platelets in both animals, with minimal side effects. Cell growth switches
      could greatly enhance the efficacy and applicability of gene and cell therapy.

PMID- 12200363
TI  - In vitro phenotypic correction of hematopoietic progenitors from Fanconi anemia
      group A knockout mice.
AB  - Fanconi anemia (FA) is a rare autosomal recessive disease, characterized by bone
      marrow failure and cancer predisposition. So far, 8 complementation groups have
      been identified, although mutations in FANCA account for the disease in the
      majority of FA patients. In this study we characterized the hematopoietic
      phenotype of a Fanca knockout mouse model and corrected the main phenotypic
      characteristics of the bone marrow (BM) progenitors using retroviral vectors. The
      hematopoiesis of these animals was characterized by a modest though significant
      thrombocytopenia, consistent with reduced numbers of BM megakaryocyte
      progenitors. As observed in other FA models, the hematopoietic progenitors from
      Fanca(-/-) mice were highly sensitive to mitomycin C (MMC). In addition, we
      observed for the first time in a FA mouse model a marked in vitro growth defect
      of Fanca(-/-) progenitors, either when total BM or when purified Lin(-)Sca-1(+)
      cells were subjected to in vitro stimulation. Liquid cultures of Fanca(-/-) BM
      that were stimulated with stem cell factor plus interleukin-11 produced low
      numbers of granulocyte macrophage colony-forming units, contained a high
      proportion of apoptotic cells, and generated a decreased proportion of
      granulocyte versus macrophage cells, compared to normal BM cultures. Aiming to
      correct the phenotype of Fanca(-/-) progenitors, purified Lin(-)Sca-1(+) cells
      were transduced with retroviral vectors encoding the enhanced green fluorescent
      protein (EGFP) gene and human FANCA genes. Lin(-)Sca-1(+) cells from Fanca(-/-)
      mice were transduced with an efficiency similar to that of samples from wild-type
      mice. More significantly, transductions with FANCA vectors corrected both the MMC
      hypersensitivity as well as the impaired ex vivo expansion ability that
      characterized the BM progenitors of Fanca(-/-) mice.

PMID- 12200365
TI  - Ectopic expression of Delta4 impairs hematopoietic development and leads to
      lymphoproliferative disease.
AB  - Notch signaling plays a critical role in cell fate determination in many
      developmental systems, including the hematopoietic system. We and others have
      recently cloned a novel Notch ligand called Delta4. In this study, we show the
      effect of retrovirus-mediated ectopic expression of Delta4 in hematopoietic
      cells. Lethally irradiated mice transplanted with bone marrow cells expressing
      Delta4 initially suffered from leukopenia and thrombocytopenia. Although all
      lineages were affected, the deficit in B cells and platelets was the most durable
      and profound. A rapid expansion of CD4(+)CD8(+) cells occurred shortly after
      transplantation. CD4(+)CD8(+) cells progressively invaded all tissues analyzed
      except the thymus, which surprisingly was atrophic. CD4(+)CD8(+) cells were
      mainly non-Delta4-transduced cells, strongly suggesting that the disease was not
      cell autonomous. Around 15 weeks after transplantation, mice died from this
      severe lymphoproliferative disorder, which was not transplantable in late-stage
      disease into secondary recipients. Mice transduced with a soluble form of Delta4
      behaved like control mice. Characterization of early hematopoietic development
      revealed that Delta4 expression impaired formation of day-12 spleen colony
      forming units (CFU-Ss) and, to a greater extent, pre-CFU-Ss. No effect was
      observed on myeloid colony-forming cells (CFU-Cs), indicating that Delta4
      specifically acted on the earliest hematopoietic stem cell compartment. These
      results show that constitutive expression of Delta4 in hematopoietic cells
      impairs the development of B cells, platelets, and early stem cells and induces a
      lethal lymphoproliferative disease.

PMID- 12200364
TI  - X-linked thrombocytopenia with thalassemia from a mutation in the amino finger of
      GATA-1 affecting DNA binding rather than FOG-1 interaction.
AB  - Transcription factor GATA-1 is essential for the development of erythroid cells
      and megakaryocytes. Each of its 2 zinc fingers is critical for normal function.
      The C-terminal finger is necessary for DNA binding. The N finger mediates
      interaction with FOG-1, a cofactor for GATA-1, and also modulates DNA-binding
      affinity, notably at complex or palindromic GATA sites. Residues of the N finger
      mediating interaction with FOG-1 lie on the surface of the N finger facing away
      from DNA. Strong sequence conservation of residues facing DNA suggests that this
      other surface may also have an important role. We report here that a syndrome of
      X-linked thrombocytopenia with thalassemia in humans is caused by a missense
      mutation (Arg216Gln) in the GATA-1 N finger. To investigate the functional
      consequences of this substitution, we used site-directed mutagenesis to alter the
      corresponding residue in GATA-1. Compared with wild-type GATA-1, Arg216Gln GATA-1
      shows comparable affinity to single GATA sites but decreased affinity to
      palindromic sites. Arg216Gln GATA-1 interacts with FOG-1 similarly with wild-type
      GATA-1. Arg216Gln GATA-1 supports erythroid maturation of GATA-1 erythroid cells,
      albeit at reduced efficiency compared with wild-type GATA-1. Together, these
      findings suggest that residues of the N finger of GATA-1-facing DNA contribute to
      GATA-1 function apart from interaction with the cofactor FOG-1. This is also the
      first example of beta-thalassemia in humans caused by a mutation in an erythroid
      transcription factor.

PMID- 12200366
TI  - A genetic and genomic analysis identifies a cluster of genes associated with
      hematopoietic cell turnover.
AB  - Hematopoietic stem cells from different strains of mice vary widely with respect
      to their cell cycle activity. In the present study we used complementary genetic
      and genomic approaches to identify molecular pathways affecting this complex
      trait. We identified a major quantitative trait locus (QTL) associated with
      variation in cell proliferation in C57BL/6 and DBA/2 mice to a 10 centimorgan
      (cM) region on chromosome 11. A congenic mouse model confirmed that a genomic
      interval on chromosome 11 in isolation confers the proliferation phenotype. To
      detect candidate genes we performed subtractive hybridizations and gene arrays
      using cDNA from highly enriched stem cells from parental strains. Intriguingly, a
      disproportionate number of differentially expressed genes mapped to chromosome 11
      and, more specifically, these transcripts occurred in 3 distinct clusters. The
      largest cluster colocalized exactly with the cell cycling QTL. Such clustering
      suggested the involvement of genetic variation that affects higher-order
      chromosomal organization. This hypothesis was reinforced by the fact that
      differentially expressed genes mapped to recombination "coldspots," as a
      consequence of which clustered genes are collectively inherited. These findings
      suggest the functional interdependence of these closely linked genes. Our data
      are consistent with the hypothesis that this isolated cell cycle QTL does not
      result from a mutation in a single gene but rather is a consequence of variable
      expression of a collection of highly linked genes.

PMID- 12200367
TI  - The cytoplasmic domain of Mpl receptor transduces exclusive signals in embryonic
      and fetal hematopoietic cells.
AB  - The Mpl receptor plays an important role at the level of adult hematopoietic stem
      cells, but little is known of its function in embryonic and fetal hematopoiesis.
      We investigated the signals sent by the MPL cytoplasmic domain in fetal liver
      hematopoietic progenitors and during embryonic stem (ES) cell hematopoietic
      commitment. Mpl was found to be expressed only from day 6 of ES cell
      differentiation into embryoid bodies. Therefore, we expressed Mpl in
      undifferentiated ES cells or in fetal progenitors and studied the effects on
      hematopoietic differentiation. To avoid the inadvertent effect of thrombopoietin,
      we used a chimeric receptor, PM-R, composed of the extracellular domain of the
      prolactin receptor (PRL-R) and the transmembrane and cytoplasmic domains of Mpl.
      This allowed activation of the receptor with a hormone that is not involved in
      hematopoietic differentiation and assessment of the specificity of responses to
      Mpl by comparing PM-R with another PRL-R chimeric receptor that includes the
      cytoplasmic domain of the erythropoietin receptor (EPO-R) ([PE-R]). We have shown
      that the cytoplasmic domain of the Mpl receptor transduces exclusive signals in
      fetal liver hematopoietic progenitors as compared with that of EPO-R and that it
      promotes hematopoietic commitment of ES cells. Our findings demonstrate for the
      first time the specific role of Mpl in early embryonic or fetal hematopoietic
      progenitors and stem cells.

PMID- 12200368
TI  - Acute thrombocytopenia after treatment with tirofiban or eptifibatide is
      associated with antibodies specific for ligand-occupied GPIIb/IIIa.
AB  - Acute thrombocytopenia is a recognized complication of treatment with GPIIb/IIIa
      inhibitors whose cause is not yet known. We studied 9 patients who developed
      severe thrombocytopenia (platelets less than 25 x 10(9)/L) within several hours
      of treatment with the GPIIb/IIIa inhibitors tirofiban (4 patients) and
      eptifibatide (5 patients). In each patient, acute-phase serum contained a high
      titer (range, 1:80-1:20 000) IgG antibody that reacted with the glycoprotein
      IIb/IIIa complex only in the presence of the drug used in treatment. Four
      patients had been previously treated with the same drug, but 5 had no known prior
      exposure. Pretreatment serum samples from 2 of the latter patients contained drug
      dependent antibodies similar to those identified after treatment. No tirofiban-
      or eptifibatide-dependent antibodies were found in any of 100 randomly selected
      healthy blood donors, and only 2 of 23 patients receiving tirofiban or
      eptifibatide who did not experience significant thrombocytopenia had extremely
      weak (titer, 1:2) tirofiban-dependent antibodies. In preliminary studies,
      evidence was obtained that the 9 antibodies recognize multiple target epitopes on
      GPIIb/IIIa complexed with the inhibitor to which the patient was sensitive,
      indicating that they cannot all be specific for the drug-binding site. The
      findings indicate that acute thrombocytopenia after the administration of
      tirofiban or eptifibatide can be caused by drug-dependent antibodies that are
      "naturally occurring" or are induced by prior exposure to drug. These antibodies
      may be human analogs of mouse monoclonal antibodies that recognize ligand-induced
      binding sites (LIBS) induced in the GPIIb/IIIa heterodimer when it reacts with a
      ligand-mimetic drug.

PMID- 12200369
TI  - The caspase inhibitor z-VAD is more effective than CD18 adhesion blockade in
      reducing muscle ischemia-reperfusion injury: implication for clinical trials.
AB  - Ischemia-reperfusion (I/R) leads to organ injury and organ dysfunction in a
      variety of clinical disorders. Preclinical investigations examining leukocyte
      adhesion molecules in I/R provided overwhelming evidence that blocking the
      function of leukocyte adhesion molecules would be highly effective in improving
      outcome in clinically relevant diseases. Unfortunately, all 9 of the recently
      completed phase 2 and 3 clinical trials examining antiadhesion therapy have
      failed. In this report, we show that a modest increase in ischemic time results
      in conversion from a CD18-dependent to a CD18-independent injury. This
      fundamental change in the mechanism of injury can be reduced by inhibition of
      caspases leading to blockade of apoptosis. Muscle injury resulting from aortic
      clamping was measured by release of creatine kinase. I/R injury following
      ischemia of 60 minutes or less and 3 hours of reperfusion was significantly
      reduced by pretreatment with anti-CD18 monoclonal antibody. However, 90 minutes
      of ischemia resulted in a marked increase in injury that was not reduced by CD18
      blockade. Importantly, the injury resulting from 90 or 120 minutes of ischemia
      was reduced by the pancaspase inhibitor z-VAD. We propose that the length of
      ischemia can result in a fundamental change in the mechanism of injury and that
      all preclinical investigations of I/R must be evaluated with increasing ischemia
      if they are to model the clinical disease. The result showing CD18-independent
      I/R injury is not unique; likewise, protection by caspase inhibitors is not
      unique. However, we show for the first time that caspase inhibitors are effective
      when CD18 blockade is not.

PMID- 12200370
TI  - A common polymorphism in the annexin V Kozak sequence (-1C>T) increases
      translation efficiency and plasma levels of annexin V, and decreases the risk of
      myocardial infarction in young patients.
AB  - Annexin V has phospholipid-binding capacity and plays a potent antithrombotic
      role. Recently, a C to T transition has been described in the Kozak region of
      this gene, affecting the nucleotide preceding the initiation ATG codon. We have
      developed a simple method to detect this genetic change, showing by analysis of
      580 Mediterranean white subjects that the -1C to T transition (-1C>T) is a common
      polymorphism (allele frequency, 0.121). This polymorphism is in linkage
      disequilibrium with a new C>G polymorphism located 27 bp downstream in intron 2.
      We show that -1C/C carriers presented significantly lower plasma levels of
      annexin V than -1C/T subjects (0.45 +/- 0.20 ng/mL versus 0.73 +/- 0.28 ng/mL,
      respectively; P =.02). In vitro transcription/translation experiments support
      that the -1T allele increases translation efficiency. The clinical relevance of
      the -1C>T change was investigated in consecutive patients with nontraumatic
      spontaneous intracranial hemorrhage (n = 225), deep venous thrombosis (n = 151),
      and coronary heart disease (n = 101). Finally, we also studied 166 survivors of
      an acute myocardial infarction occurring at age of 45 or less. This polymorphism
      seems to have a minor effect in bleeding disorders, but to play a protective role
      against early myocardial infarction, reducing by 2-fold the risk of developing
      the disease (P =.006; odds ratio, 0.51; 95% confidence interval, 0.30-0.85).

PMID- 12200371
TI  - Effects of intravenous immunoglobulin on platelet count and antiplatelet antibody
      disposition in a rat model of immune thrombocytopenia.
AB  - Experiments were conducted to investigate the effects of intravenous
      immunoglobulin (IVIG) in a rat model of immune thrombocytopenia (ITP). Rats were
      pretreated with 0 to 2 g/kg IVIG and then challenged with an antiplatelet
      antibody (7E3, 8 mg/kg). IVIG effects on 7E3-induced thrombocytopenia and on 7E3
      pharmacokinetics were determined. IVIG pretreatment led to significant changes in
      the degree and time-course of 7E3-induced thrombocytopenia (P =.031). Nadir
      percent platelet counts were 121% to 279% greater in animals treated with IVIG
      (0.4-2 g/kg) than in animals receiving 7E3 alone. IVIG treatment also led to dose
      dependent increases in 7E3 clearance (P <.001), with more than 2-fold increases
      in 7E3 clearance seen following the highest dose of IVIG. In vitro experiments
      showed that IVIG effects on platelet count are not likely due to anti-idiotypic
      inhibition of 7E3-platelet binding and that IVIG did not directly bind to 7E3.
      Consequently, IVIG-7E3 binding cannot explain the increase of 7E3 clearance
      following IVIG treatment. We propose that the observed increase in 7E3 clearance
      with IVIG therapy is due to saturation of the FcRn salvage receptor for IgG. The
      importance of the effect of IVIG on 7E3 clearance to the prevention of
      thrombocytopenia in these animals is unclear at present; nonetheless, these data
      provide experimental support for a new mechanism of IVIG action in ITP (ie, IVIG
      mediated increases in antiplatelet antibody elimination). This model of ITP will
      be useful for further investigations of IVIG mechanism of action and for
      development of new therapies for ITP.

PMID- 12200372
TI  - Disruption of the long-range GPIIIa Cys(5)-Cys(435) disulfide bond results in the
      production of constitutively active GPIIb-IIIa (alpha(IIb)beta(3)) integrin
      complexes.
AB  - The major platelet integrin alpha(IIb)beta(3), also known as the platelet
      glycoprotein (GP) IIb-IIIa complex, mediates platelet aggregation by serving as
      the receptor for fibrinogen and von Willebrand factor. In addition to its
      physiologic role, GPIIb-IIIa also bears a number of clinically important
      alloantigenic determinants. Previous studies have shown that disruption of the
      long-range Cys(5)-Cys(435) disulfide bond of the beta(3) subunit results in the
      production of isoforms that bind some, but not all, anti-Pl(A1) alloantibodies,
      suggesting that mutations in this so-called long-range disulfide bond can alter
      the conformation of GPIIIa. The purpose of this study was to examine the effects
      of either the Cys5Ala or Cys435Ala substitution of GPIIIa on the adhesive
      properties of the GPIIb-IIIa complex. We found that both Ala5GPIIIa and
      Ala435GPIIIa were capable of associating with GPIIb and were expressed normally
      on the cell surface when cotransfected into Chinese hamster ovary (CHO) cells.
      CHO cells expressing GPIIb-Ala5GPIIIa or GPIIb-Ala435IIIa bound well
      characterized, conformationally sensitive ligand-induced binding site (LIBS)
      antibodies, and were capable of constitutively binding the fibrinogen-mimetic
      monoclonal antibodies Pl-55 and PAC-1, as well as soluble fibrinogen. Both GPIIb
      Ala5IIIa- and GPIIb-Ala435IIIa-transfected CHO cells also bound more avidly to
      immobilized fibrinogen and were capable of mediating the tyrosine phosphorylation
      of pp125(FAK) on cell adhesion. These data are consistent with the notion that
      these regions of GPIIIa participate in the conformational change associated with
      receptor activation. Additionally, these studies may provide a molecular
      explanation for the previously reported ability of mild reducing agents to
      activate the GPIIb-IIIa complex and promote platelet aggregation.

PMID- 12200373
TI  - Amelioration of the macrothrombocytopenia associated with the murine Bernard
      Soulier syndrome.
AB  - An absent platelet glycoprotein (GP) Ib-IX receptor results in the Bernard
      Soulier syndrome and is characterized by severe bleeding and the laboratory
      presentation of macrothrombocytopenia. Although the macrothrombocytopenic
      phenotype is directly linked to an absent GP Ib-IX complex, the disrupted
      molecular mechanisms that produce the macrothrombocytopenia are unknown. We have
      utilized a mouse model of the Bernard-Soulier syndrome to engineer platelets
      expressing an alpha-subunit of GP Ib (GP Ibalpha) in which most of the
      extracytoplasmic sequence has been replaced by an isolated domain of the alpha
      subunit of the human interleukin-4 receptor (IL-4Ralpha). The IL-4Ralpha/GP
      Ibalpha fusion is membrane expressed in Chinese hamster ovary (CHO) cells, and
      its expression is facilitated by the presence of human GP IX and the beta-subunit
      of GP Ib. Transgenic animals expressing a chimeric receptor were generated and
      bred into the murine Bernard-Soulier syndrome-producing animals devoid of mouse
      GP Ibalpha but expressing the IL-4Ralpha/GP Ibalpha fusion sequence. The
      characterization of these mice revealed a 2-fold increase in circulating platelet
      count and a 50% reduction in platelet size when compared with platelets from the
      mouse model of the Bernard-Soulier syndrome. Immunoprecipitation confirmed that
      the IL-4Ralpha/GP Ibalpha subunit interacts with filamin-1 and 14-3-3zeta, known
      binding proteins to the GP Ibalpha cytoplasmic tail. Mice expressing the chimeric
      receptor retain a severe bleeding phenotype, confirming a critical role for the
      GP Ibalpha extracytoplasmic domain in hemostasis. These results provide in vivo
      insights into the structural elements of the GP Ibalpha subunit that contribute
      to normal megakaryocyte maturation and thrombopoiesis.

PMID- 12200374
TI  - Effect of hyperhomocysteinemia on protein C activation and activity.
AB  - Hyperhomocysteinemia has been proposed to inhibit the protein C anticoagulant
      system through 2 mechanisms: decreased generation of activated protein C (APC) by
      thrombin, and resistance to APC caused by decreased inactivation of factor Va
      (FVa). We tested the hypotheses that generation of APC by thrombin is impaired in
      hyperhomocysteinemia in monkeys and that hyperhomocysteinemia produces resistance
      to APC in monkeys, mice, and humans. In a randomized crossover study, cynomolgus
      monkeys were fed either a control diet or a hyperhomocysteinemic diet for 4
      weeks. Plasma total homocysteine (tHcy) was approximately 2-fold higher when
      monkeys were on the hyperhomocysteinemic diet than when they were on the control
      diet (9.8 +/- 2.0 microM versus 5.6 +/- 1.0 microM; P <.05). After infusion of
      human thrombin (25 microg/kg of body weight), the peak level of plasma APC was
      136 +/- 16 U/mL in monkeys fed the control diet and 127 +/- 13 U/mL in monkeys
      fed the hyperhomocysteinemic diet (P >.05). The activated partial thromboplastin
      time was prolonged to a similar extent by infusion of thrombin in monkeys fed the
      control diet and in those fed the hyperhomocysteinemic diet. The sensitivity of
      plasma FV to human APC was identical in monkeys on control diet and those on
      hyperhomocysteinemic diet. We also did not detect resistance of plasma FV to APC
      in hyperhomocysteinemic mice deficient in cystathionine beta-synthase (plasma
      tHcy, 93 +/- 16 microM) or in human volunteers with acute hyperhomocysteinemia
      (plasma tHcy, 45 +/- 6 microM). Our findings indicate that activation of protein
      C by thrombin and inactivation of plasma FVa by APC are not impaired during
      moderate hyperhomocysteinemia in vivo.

PMID- 12200375
TI  - Normal Arp2/3 complex activation in platelets lacking WASp.
AB  - Arp2/3 complex is believed to induce de novo nucleation of actin filaments at the
      edge of motile cells downstream of WASp family proteins. In this study, the
      signaling pathways leading to Arp2/3 complex activation, actin assembly, and
      shape change were investigated in platelets isolated from patients with Wiskott
      Aldrich Syndrome (WAS), that is, who lack WASp, and in WASp-deficient mouse
      platelets. WASp-deficient human and mouse platelets elaborate filopodia, spread
      lamellae, and assemble actin, identical to control WASp-expressing platelets.
      Human platelets contain 2 microM Arp2/3 complex, or 8600 molecules/cell. Arp2/3
      complex redistributes to the edge of the lamellae and to the Triton X-100
      insoluble actin cytoskeleton of activated WASp-deficient platelets. Furthermore,
      the C-terminal CA domain of N-WASp, which sequesters Arp2/3 complex, inhibits by
      half the actin nucleation capacity of octylglucoside-permeabilized and activated
      WAS platelets, similar to its effect in WASp-expressing cells. Along with WASp,
      platelets express WAVE-2 as a physiologic activator of Arp2/3 complex and a small
      amount of N-WASp. Taken together, our findings show that platelets activate
      Arp2/3 complex, assemble actin, and change shape in the absence of WASp,
      indicating a more specialized role for WASp in these cells.

PMID- 12200376
TI  - Identification of tumor-associated antigens in chronic lymphocytic leukemia by
      SEREX.
AB  - Chronic lymphocytic leukemia (CLL) is associated with a variety of immunologic
      disturbances. Hypogammaglobulinemia and autoimmune phenomena are both often
      present in this disease. In contrast, humoral or cellular antitumor responses are
      rarely observed. It has been previously shown that antigens detected in patients
      with malignant diseases can provide information regarding intracellular molecules
      engaged in the transformation process and can identify tumor antigens that may be
      useful for development of immunotherapeutic strategies. Serologic identification
      by recombinant expression cloning (SEREX) has been demonstrated to be a useful
      method to detect tumor and tumor-associated antigens in a variety of
      malignancies. Although this approach is complicated in CLL, we used a modified
      SEREX approach and identified 14 antigens (KW-1 to KW-14) using this methodology.
      Several clones showed a restricted expression pattern in normal tissues.
      Moreover, distinctive expression of splice variants and aberrant gene expression
      in malignant tissue were detected. In this study, 6 antigens were detected
      exclusively in patients with CLL. Eight antigens were detected also in lymphoma
      patients. Healthy donors showed antibody responses against only 3 of the
      identified antigens. T cells with specific cytotoxicity against peptides derived
      from the 2 antigens tested could be generated from healthy donors. These findings
      demonstrate that humoral and cellular immune responses against CLL-associated
      antigens can be detected. Ongoing experiments investigate their potential for the
      development of immunotherapeutic strategies.

PMID- 12200377
TI  - CD8 T-cell responses to Wilms tumor gene product WT1 and proteinase 3 in patients
      with acute myeloid leukemia.
AB  - Wilms tumor gene product WT1 and proteinase 3 are overexpressed antigens in acute
      myeloid leukemia (AML), against which cytotoxic T lymphocytes can be elicited in
      vitro and in murine models. We performed this study to investigate whether WT1-
      and proteinase 3-specific CD8 T cells spontaneously occur in AML patients. T
      cells recognizing HLA-A2.1-binding epitopes from WT1 or proteinase 3 could be
      detected ex vivo in 5 of 15 HLA-A2-positive AML patients by interferon-gamma (IFN
      gamma) ELISPOT assay and flow cytometry for intracellular IFN-gamma and in 3
      additional patients by flow cytometry only. T cells producing IFN-gamma in
      response to proteinase 3 were further characterized in one patient by 4-color
      flow cytometry, identifying them as CD3(+)CD8(+)CD45RA(+) CCR7(-) T cells,
      resembling cytotoxic effector T cells. In line with this phenotype, most of the
      WT1- and proteinase-reactive T cells were granzyme B(+). These results provide
      for the first time evidence for spontaneous T-cell reactivity against defined
      antigens in AML patients. These data therefore support the immunogenicity of WT1
      and proteinase 3 in acute leukemia patients and the potential usefulness of these
      antigens for leukemia vaccines.

PMID- 12200378
TI  - Regulation of FcepsilonRI-mediated degranulation by an adaptor protein 3BP2 in
      rat basophilic leukemia RBL-2H3 cells.
AB  - Aggregation of high-affinity IgE receptor FcepsilonRI induces sequential
      activation of nonreceptor-type protein-tyrosine kinases and subsequent tyrosine
      phosphorylation of cellular proteins, leading to degranulation in mast cells. A
      hematopoietic cell-specific adaptor protein, 3BP2, that was originally identified
      as an Abl SH3-binding protein was rapidly tyrosine phosphorylated by the
      aggregation of FcepsilonRI on rat basophilic leukemia RBL-2H3 cells. Tyrosine
      phosphorylation of 3BP2 did not depend on calcium influx from external sources.
      To examine the role of 3BP2 in mast cells, we overexpressed the SH2 domain of
      3BP2 in the RBL-2H3 cells. Overexpression of 3BP2-SH2 domain resulted in a
      suppression of antigen-induced degranulation as assessed by beta-hexosaminidase
      release. Even though overall tyrosine phosphorylation of cellular protein was not
      altered, antigen-mediated tyrosine phosphorylation of phospholipase C-gamma (PLC
      gamma) and calcium mobilization were significantly suppressed in the cells
      overexpressing the 3BP2-SH2 domain. Furthermore, antigen stimulation induced the
      association of 3BP2-SH2 domain with LAT and other signaling molecule complexes in
      the RBL-2H3 cells. FcepsilonRI-mediated phosphorylation of JNK and ERK was not
      affected by the overexpression of 3BP2-SH2 domain. These data indicate that 3BP2
      functions to positively regulate the FcepsilonRI-mediated tyrosine
      phosphorylation of PLC-gamma and thereby the signals leading to degranulation.

PMID- 12200379
TI  - The immunophenotypic and immunogenotypic B-cell differentiation arrest in bone
      marrow of RAG-deficient SCID patients corresponds to residual recombination
      activities of mutated RAG proteins.
AB  - The protein products of the recombination activating genes (RAG1 and RAG2)
      initiate the formation of immunoglobulin (Ig) and T-cell receptors, which are
      essential for B- and T-cell development, respectively. Mutations in the RAG genes
      result in severe combined immunodeficiency disease (SCID), generally
      characterized by the absence of mature B and T lymphocytes, but presence of
      natural killer (NK) cells. Biochemically, mutations in the RAG genes result
      either in nonfunctional proteins or in proteins with partial recombination
      activity. The mutated RAG genes of 9 patients from 7 families were analyzed for
      their recombination activity using extrachromosomal recombination substrates,
      rearrangement of endogenous Ig loci in RAG gene-transfected nonlymphoid cells, or
      the presence of Ig gene rearrangements in bone marrow (BM). Recombination
      activity was virtually absent in all 6 patients with mutations in the RAG core
      domains, but partial activity was present in the other 3 RAG-deficient patients,
      2 of them having Omenn syndrome with oligoclonal T lymphocytes. Using 4-color
      flow cytometry, we could define the exact stage at which B-cell differentiation
      was arrested in the BM of 5 RAG-deficient SCID patients. In 4 of 5 patients, the
      absence of recombination activity was associated with a complete B-cell
      differentiation arrest at the transition from cytoplasmic (Cy) Igmu(-) pre-B-I
      cells to CyIgmu(+) pre-B-II cells. However, the fifth patient showed low
      frequencies of precursor B cells with CyIgmu and surface membrane IgM, in line
      with the partial recombination activity of the patient's mutated RAG gene and the
      detection of in-frame Ig gene rearrangements in BM.

PMID- 12200380
TI  - Human fetuses are able to mount an adultlike CD8 T-cell response.
AB  - Fetal/neonatal immune responses generally are considered to be immature and
      weaker than that of adults. We have studied the cord-blood T cells of newborns
      congenitally infected with Trypanosoma cruzi, the protozoan agent of Chagas
      disease. Our data demonstrate a predominant activation of CD8 T cells expressing
      activation markers and armed to mediate effector functions. The analysis of the T
      cell receptor beta chain variable repertoire shows the oligoclonal expansion of
      these T lymphocytes, indicating that activation was driven by parasite antigens.
      Indeed, we have detected parasite-specific CD8 T cells secreting interferon-gamma
      after coincubation with live T cruzi. This response is enhanced in the presence
      of recombinant interleukin-15, which limits the T-cell spontaneous apoptosis.
      These findings point out that the fetal immune system is more competent than
      previously appreciated, since fetuses exposed to live pathogens are able to
      develop an adultlike immune CD8 T-cell response.

PMID- 12200381
TI  - Long-term effects of intermittent interleukin 2 therapy in patients with HIV
      infection: characterization of a novel subset of CD4(+)/CD25(+) T cells.
AB  - The long-term immunologic effects of intermittent interleukin 2 (IL-2) therapy
      were evaluated in a cross-sectional study by comparing 3 groups: HIV-seronegative
      volunteers, HIV-infected (HIV(+)) patients receiving highly active antiretroviral
      therapy (HAART), and HIV(+) patients receiving HAART and intermittent IL-2. Whole
      blood immunophenotyping was performed to study expression of the IL-2 receptor
      chains on T lymphocytes and natural killer cells and to further characterize
      CD4(+)/CD25(+) T cells. Increased CD25 expression, especially in CD4(+) T cells
      but also in CD8(+) T cells, without increases in expression of the beta and gamma
      chains of the IL-2 receptor was detected in the IL-2 group. Up to 79% of naive
      CD4(+) T cells (median, 61%) from patients in the IL-2 group expressed CD25, and
      the number of naive CD4(+)/CD25(+) T cells correlated positively with both the
      total and naive CD4(+) T-cell counts. A discrete population of CD45 double
      intermediate RA(+)/RO(+) CD4(+) cells was also preferentially expanded in the IL
      2 group, and the number of these cells strongly correlated with the total CD4(+)
      count. Despite increases in CD25 expression, T lymphocytes from patients treated
      with IL-2 did not have increased expression of early (CD69) or late (CD95)
      activation markers or evidence of recent proliferation (Ki67). Both
      CD4(+)/CD25(+) and CD4(+)/CD25(-) cells from IL-2-treated HIV(+) patients
      proliferated in response to mitogens, specific antigens, and T-cell-receptor
      mediated stimuli. Thus, intermittent administration of IL-2 in HIV(+) patients
      leads to preferential expansion of a unique subset of CD4(+) T cells that may
      represent a critical population in T-cell homeostasis.

PMID- 12200382
TI  - A prospective study on the evolution of the T-cell repertoire in patients with
      Sezary syndrome treated by extracorporeal photopheresis.
AB  - Sezary syndrome is a leukemic form of epidermotropic cutaneous T-cell lymphoma
      related to the malignant proliferation of clonal CD4(+) T cells. Extracorporeal
      photochemotherapy may induce a transient improvement of the clinical signs, but
      its efficiency is discussed. To investigate the frequency of the T-cell clone in
      the peripheral blood of patients with Sezary syndrome and to monitor its
      evolution in patients treated using extracorporeal photopheresis or chemotherapy,
      we used the immunoscope technique. In one patient, we observed a decrease of the
      relative frequency of the clone from 15.6% to 0%, paralleling a complete
      remission of the clinical disease and a disappearance of the circulating Sezary
      cells. In the other cases, the evolution of the relative frequency paralleled the
      initial improvement of the clinical status and the absence of long-term
      efficiency in patients treated with extracorporeal photopheresis or chemotherapy.
      We observed a quick-acting direct cytotoxicity of the association 8MOP + UVA on
      the T-cell clone. The immunoscope technique appears to be an efficient tool to
      appreciate the amount of tumoral cells and to monitor the evolution of the clonal
      component in the Sezary syndrome.

PMID- 12200384
TI  - 2-Methoxyestradiol overcomes drug resistance in multiple myeloma cells.
AB  - 2-Methoxyestradiol (2ME2) an estrogen derivative, induces growth arrest and
      apoptosis in leukemic cells and is also antiangiogenic. In this study, we
      demonstrate that 2ME2 inhibits growth and induces apoptosis in multiple myeloma
      (MM) cell lines and patient cells. Significantly, 2ME2 also inhibits growth and
      induces apoptosis in MM cells resistant to conventional therapies including
      melphalan (LR-5), doxorubicin (Dox-40 and Dox-6), and dexamethasone (MM.1R). In
      contrast to its effects on MM cells, 2ME2 does not reduce the survival of normal
      peripheral blood lymphocytes. Moreover, 2ME2 enhances Dex-induced apoptosis, and
      its effect is not blocked by interleukin-6 (IL-6). We next examined the effect of
      2ME2 on MM cells in the bone marrow (BM) milieu. 2ME2 decreases survival of BM
      stromal cells (BMSCs), as well as secretion of vascular endothelial growth factor
      (VEGF), and IL-6 triggered by the adhesion of MM cells to BMSCs. We show that
      apoptosis induced by 2ME2 is mediated by the release of mitochondrial cytochrome
      c (cyto-c) and Smac, followed by the activation of caspases-8, -9, and -3.
      Finally, 2ME2 inhibits MM cell growth, prolongs survival, and decreases
      angiogenesis in a murine model. These studies, therefore, demonstrate that 2ME2
      mediates anti-MM activity directly on MM cells and in the BM microenvironment.
      They provide a framework for the use of 2ME2, either alone or in combination with
      Dex, to overcome drug resistance and to improve outcome in MM.

PMID- 12200385
TI  - Role for macrophage inflammatory protein (MIP)-1alpha and MIP-1beta in the
      development of osteolytic lesions in multiple myeloma.
AB  - Multiple myeloma (MM) cells cause devastating bone destruction by activating
      osteoclasts in the bone marrow milieu. However, the mechanism of enhanced bone
      resorption in patients with myeloma is poorly understood. In the present study,
      we investigated a role of C-C chemokines, macrophage inflammatory protein (MIP)
      1alpha and MIP-1beta, in MM cell-induced osteolysis. These chemokines were
      produced and secreted by a majority of MM cell lines as well as primary MM cells
      from patients. Secretion of MIP-1alpha and MIP-1beta correlated well with the
      ability of myeloma cells to enhance osteoclastic bone resorption both in vitro
      and in vivo as well as in MM patients. In osteoclastogenic cultures of rabbit
      bone cells, cocultures with myeloma cells as well as addition of myeloma cell
      conditioned media enhanced both formation of osteoclastlike cells and resorption
      pits to an extent comparable to the effect of recombinant MIP-1alpha and MIP
      1beta. Importantly, these effects were mostly reversed by neutralizing antibodies
      against MIP-1alpha and MIP-1beta, or their cognate receptor, CCR5, suggesting
      critical roles of these chemokines. We also demonstrated that stromal cells
      express CCR5 and that recombinant MIP-1alpha and MIP-1beta induce expression of
      receptor activator of nuclear factor-kappaB (RANK) ligand by stromal cells,
      thereby stimulating osteoclast differentiation of preosteoclastic cells. These
      results suggest that MIP-1alpha and MIP-1beta may be major osteoclast-activating
      factors produced by MM cells.

PMID- 12200386
TI  - Hydrocortisone reduced in vivo, inflammation-induced slow rolling of leukocytes
      and their extravasation into human conjunctiva.
AB  - Hydrocortisone reduces the number of inflammatory leukocytes within tissues, but
      thus far the site of action on the multistep adhesion cascade leading to
      leukocyte extravasation has not been identified. We have recently developed a
      noninvasive in vivo reflected-light confocal microscopy technique to study this
      at sites of inflammation in human patients. In the present study, we evaluated
      the effect of preoperative intravenous hydrocortisone treatment on leukocyte
      trafficking after conjunctival inflammation induced by cataract surgery in human
      subjects in vivo. The surgery generated leukocyte rolling along the endothelial
      lining of conjunctival vessels. While preoperative hydrocortisone did not reduce
      the number of rolling cells, it significantly raised the velocity of individual
      rolling leukocytes and concomitantly reduced leukocyte emigration into
      conjunctival tissue. Immunohistology of conjunctival biopsies excised from the
      individuals studied provided circumstantial evidence that endothelial P-selectin
      might play a role in the surgery-induced up-regulation of the leukocyte rolling.
      Furthermore, hydrocortisone reduced surgery-induced P-selectin induction,
      suggesting a role for this selectin in the regulation of local leukocyte traffic
      into sites of inflammation in human conjunctiva. Taken together, these results
      suggest that control of the rolling velocity might be an effective way to adjust
      leukocyte traffic in vivo in human subjects.

PMID- 12200387
TI  - Splenectomy prolongs in vivo survival of erythrocytes differently in
      spectrin/ankyrin- and band 3-deficient hereditary spherocytosis.
AB  - Red cell (RBC) deformability and membrane-bound immunoglobulin G (IgG) were
      studied to better understand premature clearance of erythrocytes in hereditary
      spherocytosis. Averaged deformability profiles from cells having comparable cell
      age revealed that splenectomy was more beneficial for spectrin/ankyrin-deficient
      than for band 3-deficient RBCs. Splenectomy prevented an early loss of young
      cells in both types of deficiencies. It had an additional beneficial effect on
      spectrin/ankyrin-deficient but not band 3-deficient RBCs. It prolonged the
      survival of mature spectrin/ankyrin-deficient RBCs such that they lost their
      deformability more slowly than RBCs from patients who had not undergone
      splenectomy. Band 3-deficient RBCs lost their deformability at the same rate
      before and after splenectomy. In HS patients with band 3 deficiency who underwent
      splenectomy, RBC deformability inversely correlated with the number of RBC-bound
      IgG (up to 140 molecules per cell). In spectrin/ankyrin deficiency, RBC-bound IgG
      remained at control levels (60 IgG or less per cell). It appears that
      spectrin/ankyrin-deficient RBCs escaped opsonization by releasing band 3
      containing vesicles because their band 3 content and deformability dropped in
      parallel with increasing cell age. Band 3-deficient RBCs did not lose band 3 with
      increasing cell age. Hence, it is possible that band 3 clusters required for
      bivalent binding of low-affinity-IgG, naturally occurring antibodies were
      retained in band 3-deficient RBCs with a relative excess of skeletal proteins but
      were released from spectrin/ankyrin-deficient RBCs, in which vesicle budding was
      facilitated by an impaired skeleton.

PMID- 12200388
TI  - Aberrant regulation of superantigen responses during T-cell reconstitution and
      graft-versus-host disease in immunodeficient mice.
AB  - Acute graft-versus-host disease (GVHD) after allogeneic stem cell transplantation
      is associated with impaired deletion and anergy of host-reactive T cells. To
      elucidate the immunoregulatory events that may contribute to such dysregulated T
      cell responses in GVHD, we studied superantigen (SAg) responses after adoptive T
      cell transfer into severe combined immunodeficient (SCID) mice. SAg responses are
      normally regulated by mechanisms involving deletion and anergy, with SAg-reactive
      T cells typically being deleted rapidly in vivo. In a SCID mouse model of GVHD,
      however, allogeneic host SAg-reactive T cells were not deleted rapidly, but
      rather persisted in increased numbers for several months. Moreover, depending on
      the timing of SAg stimulation and the numbers of T cells transferred,
      dysregulation (impaired deletion and anergy) of SAg responses could be
      demonstrated following the adoptive transfer of syngeneic T cells into SCID mice
      as well. Transgenic T-cell receptor-bearing KJ1-26.1(+) T cells were then used to
      determine the fate of weakly reactive T cells after adoptive transfer and SAg
      stimulation. When transferred alone, KJ1-26.1(+) T cells demonstrated impaired
      deletion and anergy. In the presence of more strongly staphylococcal enterotoxin
      B (SEB)-reactive T cells, however, KJ1-26.1(+) T cells were regulated normally,
      in a manner that could be prevented by inhibiting the effects of more strongly
      SEB-reactive cells or by increasing the level of activation of the KJ1-26.1(+) T
      cells themselves. We suggest that the control mechanisms that normally regulate
      strongly activated T cells in immunocompetent animals are lost following adoptive
      transfer into immunodeficient hosts, and that this impairment contributes to the
      development of GVHD.

PMID- 12200389
TI  - High-level allogeneic chimerism achieved by prenatal tolerance induction and
      postnatal nonmyeloablative bone marrow transplantation.
AB  - Clinical application of allogeneic bone marrow transplantation (BMT) has been
      limited by toxicity related to cytoreductive conditioning and immune response. In
      utero hematopoietic stem cell transplantation (IUHSCT) is a nonablative approach
      that achieves mixed chimerism and donor-specific tolerance but has been limited
      by minimal engraftment. We hypothesized that mixed chimerism achieved by IUHSCT
      could be enhanced after birth by nonmyeloablative total body irradiation (TBI)
      followed by same-donor BMT. To test this hypothesis, mixed chimerism was created
      by IUHSCT in a major histocompatibility complex-mismatched strain combination.
      After birth, chimeric animals received nonmyeloablative TBI followed by
      transplantation of donor congenic bone marrow cells. Our results show that: (1)
      low-level chimerism after IUHSCT can be enhanced to high-level chimerism by this
      strategy; (2) enhancement of chimerism is dependent on dose of TBI; (3) the
      mechanism of TBI enhancement is via a transient competitive advantage for
      nonirradiated hematopoietic stem cells; (4) engraftment observed in the tolerant,
      fully allogeneic IUHSC transplant recipient is equivalent to a congenic
      recipient; and (5) host-reactive donor lymphocytes are deleted with no evidence
      of graft-versus-host disease. This study supports the concept of prenatal
      tolerance induction to facilitate nonmyeloablative postnatal strategies for
      cellular therapy. If clinically applicable, such an approach could dramatically
      expand the application of IUHSCT.

PMID- 12200383
TI  - A molecular compendium of genes expressed in multiple myeloma.
AB  - We have created a molecular resource of genes expressed in primary malignant
      plasma cells using a combination of cDNA library construction, 5' end single-pass
      sequencing, bioinformatics, and microarray analysis. In total, we identified 9732
      nonredundant expressed genes. This dataset is available as the Myeloma Gene Index
      (www.uhnres.utoronto.ca/akstewart_lab).Predictably, the sequenced profile of
      myeloma cDNAs mirrored the known function of immunoglobulin-producing, high
      respiratory rate, low-cycling, terminally differentiated plasma cells.
      Nevertheless, approximately 10% of myeloma-expressed sequences matched only
      entries in the database of Expressed Sequence Tags (dbEST) or the high-throughput
      genomic sequence (htgs) database. Numerous novel genes of potential biologic
      significance were identified. We therefore spotted 4300 sequenced cDNAs on glass
      slides creating a myeloma-enriched microarray. Several of the most highly
      expressed genes identified by sequencing, such as a novel putative disulfide
      isomerase (MGC3178), tumor rejection antigen TRA1, heat shock 70-kDa protein 5,
      and annexin A2, were also differentially expressed between myeloma and B lymphoma
      cell lines using this myeloma-enriched microarray. Furthermore, a defined subset
      of 34 up-regulated and 18 down-regulated genes on the array were able to
      differentiate myeloma from nonmyeloma cell lines. These not only include genes
      involved in B-cell biology such as syndecan, BCMA, PIM2, MUM1/IRF4, and XBP1, but
      also novel uncharacterized genes matching sequences only in the public databases.
      In summary, our expressed gene catalog and myeloma-enriched microarray contains
      numerous genes of unknown function and may complement other commercially
      available arrays in defining the molecular portrait of this hematopoietic
      malignancy. GenBank Accession numbers include BF169967-BF176369, BF185966
      BF185969, and BF177280-BF177455.

PMID- 12200390
TI  - Direct evidence for new T-cell generation by patients after either T-cell
      depleted or unmodified allogeneic hematopoietic stem cell transplantations.
AB  - Successful allogeneic hematopoietic stem cell transplantation (HSCT) requires
      reconstitution of normal T-cell immunity. Recipient thymic activity, biologic
      features of the allograft, and preparative regimens all contribute to immune
      reconstitution. We evaluated circulating T-cell phenotypes and T-cell receptor
      rearrangement excision circles (TRECs) in 331 blood samples from 158 patients who
      had undergone allogeneic HSCTs. All patients had received myeloablative
      conditioning regimens and were full donor chimeras in remission. Younger patients
      exhibited more rapid recovery and higher TRECs (P =.02). Recipients of T-cell
      depleted allografts initially had lower TRECs than unmodified allograft
      recipients (P <.01), but the difference abated beyond 9 months. TREC level
      disparities did not achieve significance among adults with respect to type of
      allograft. Measurable, albeit low, TREC values correlated strongly with severe
      opportunistic infections (P <.01). This finding was most notable during the first
      6 months after transplantation, when patients are at greatest risk but before
      cytofluorography can detect circulating CD45RA(+) T cells. Low TRECs also
      correlated strongly with extensive chronic graft-versus-host disease (P <.01).
      Recipients of all ages of either unmodified or T-cell-depleted allografts
      therefore actively generate new T cells. This generation is most notable among
      adult recipients of T-cell-depleted allografts, most of whom had also received
      antithymocyte globulin for rejection prophylaxis. Low TREC values are
      significantly associated with morbidity and mortality after transplantation. T
      cell neogenesis, appropriate to age but delayed in adult recipients of T-cell
      depleted allografts, justifies interventions to hasten this process and to
      stimulate desirable cellular immune responses.

PMID- 12200391
TI  - Evidence for a graft-versus-leukemia effect after allogeneic peripheral blood
      stem cell transplantation with reduced-intensity conditioning in acute
      myelogenous leukemia and myelodysplastic syndromes.
AB  - We report the results of a prospective study of a reduced-intensity conditioning
      (RIC) regimen followed by allogeneic peripheral blood stem cell transplantation
      (PBSCT) from an HLA-identical sibling in 37 patients with acute myeloid leukemia
      (AML; n = 17) or myelodysplastic syndrome (MDS; n = 20). The median age was 57
      years, and 22 (59%) were beyond the early phase of their disease. The incidence
      of grade II to IV acute graft-versus-host disease (GVHD) was 19% (5% grade III
      IV), and the 1-year incidence of chronic extensive GVHD was 46%. With a median
      follow-up of 297 days (355 days in 24 survivors), the 1-year probability of
      transplant-related mortality was 5%, and the 1-year progression-free survival was
      66%. The 1-year incidence of disease progression in patients with and without
      GVHD was 13% (95% CI, 4%-34%) and 58% (95% CI, 36%-96%), respectively (P =.008).
      These results suggest that a graft-versus-leukemia effect plays a crucial role in
      reducing the risk of relapse after a RIC allograft in AML and MDS.

PMID- 12200392
TI  - Anemia and iron overload due to compound heterozygosity for novel ceruloplasmin
      mutations.
AB  - Aceruloplasminemia is a recessive disorder characterized by anemia, iron
      overload, and neurodegeneration, caused by the absence of ceruloplasmin (Cp), a
      multicopper oxidase important for iron export. Few patients homozygous for loss
      of function mutations of the Cp gene have been reported. We describe a 62-year
      old white woman with heavy liver iron overload, diabetes, anemia, and neurologic
      symptoms. She was compound heterozygote for 2 novel mutations that result in the
      absence of hepatocyte Cp: an adenine insertion at nucleotide 2917 causing a
      truncated protein and a C-G transversion causing a glutamine-->glutamic acid
      substitution at position 146. Although rare in whites, aceruloplasminemia should
      be considered in the differential diagnosis of unexplained anemia associated with
      iron overload, because these features anticipate progressive neurologic symptoms.
      We propose that anemia, secondary to the impaired macrophage iron release, plays
      a major role in hepatic iron overload through increased absorption mediated by
      the erythroid regulator.

PMID- 12200393
TI  - Prolongation of cardiac repolarization by arsenic trioxide.
AB  - Arsenic trioxide (As(2)O(3); ATO) has recently been found to be very effective
      for relapsed acute promyelocytic leukemia. Several articles reported prolongation
      of QT interval or ventricular arrhythmias in patients receiving ATO. However, the
      QT-prolonging effect has not been confirmed and the direct membrane effect of ATO
      has never been studied. In the present investigation, using conventional action
      potential recording technique, we found that ATO dose dependently prolonged
      action potential duration (APD) in guinea pig papillary muscle with a slow pacing
      frequency. Parenteral administration of ATO prolonged QT interval and APD in
      guinea pig hearts. Intravenous infusion of clinically relevant doses of ATO
      prolonged QT interval and APD dose dependently. These studies suggest that ATO
      has a direct effect on cardiac repolarization. Patients who are receiving ATO
      should avoid concomitant administration of other QT-prolonging agents or
      conditions in favor of delaying cardiac repolarization.

PMID- 12200394
TI  - DNB: a partial D with anti-D frequent in Central Europe.
AB  - To improve routine D typing and define transfusion strategy, it is important to
      establish the frequency of partial D alleles and their susceptibility to anti-D
      alloimmunization due to transfusion or pregnancy. We identified the partial D DNB
      that was caused by an RHD(G355S) allele associated with a CDe haplotype and whose
      phenotype presented a normal D in routine typing. The antigen density was about
      6000 D antigens per red blood cell, and the Rhesus index was 0.02. Five anti-D
      immunization events with allo-anti-D titers up to 128 were observed. Twelve
      carriers of DNB were whites of Central Europe; the only Danish proband had
      Austrian ancestry. DNB was the most frequent partial D recognized so far in
      whites, occurring with frequencies of up to 1:292 in Switzerland. DNB was the
      underlying partial D phenotype in a relevant fraction of anti-D immunizations
      occurring in whites.

PMID- 12200395
TI  - Rituximab treatment results in impaired secondary humoral immune responsiveness.
AB  - In lymphoma patients, treatment with chimeric CD20 monoclonal antibodies
      (rituximab) results in a depletion of normal and malignant B cells, persisting
      for 6 to 9 months. This B-cell depletion leads neither to a decrease in
      immunoglobulin levels nor an increase in the number of infectious complications.
      However, the effect of rituximab treatment on the immune responsiveness is
      unknown. In 11 patients with relapsed, low-grade lymphoma, we investigated the
      effect of rituximab treatment on the humoral immune response to 2 primary
      antigens and 2 recall antigens. After rituximab treatment, the humoral immune
      response to the recall antigens was significantly decreased when compared with
      the response before treatment. Already before rituximab treatment, none of these
      patients was able to mount a response to the primary antigens. These findings are
      relevant regarding the feasibility of rituximab in maintenance treatment and may
      also offer a rationale for the treatment of antibody-mediated autoimmune diseases
      with rituximab.

PMID- 12200396
TI  - Rituximab treatment of refractory fludarabine-associated immune thrombocytopenia
      in chronic lymphocytic leukemia.
AB  - Fludarabine can exacerbate idiopathic thrombocytopenia (ITP) in chronic
      lymphocytic leukemia (CLL). We report 3 CLL patients with refractory fludarabine
      associated ITP who responded to rituximab. The patients had Rai stages III, III,
      and IV disease. Before fludarabine treatment, the platelet counts were 141
      000/microL, 118 000/microL, and 70 000/microL. ITP developed within week 1 of
      cycle 3 in 2 patients and within week 2 of cycle 1 in 1 patient. Platelet count
      nadirs were 4000/microL, 1000/microL, and 2000/microL, respectively, and did not
      respond to treatment with steroids or intravenous immunoglobulin. Rituximab
      therapy (375 mg/m(2) per week for 4 weeks) was begun on days 18, 23, and 20 of
      ITP. Patient 1 achieved a platelet count of more than 50 000/microL at day 21 and
      more than 133 000/microL at day 28, patient 2 achieved a platelet count of more
      than 50 000/microL at day 4 and more than 150 000/microL at day 10, and patient 3
      achieved a platelet count of more than 50 000/microL at day 5 and 72 000/microL
      at day 28 of rituximab therapy, with platelet response durations of 17+, 6+, and
      6 months. These results suggest rituximab can rapidly reverse refractory
      fludarabine-associated ITP.

PMID- 12200397
TI  - Polymorphisms of the tumor necrosis factor-alpha gene promoter predict for
      outcome after thalidomide therapy in relapsed and refractory multiple myeloma.
AB  - Thalidomide (Thal) is a drug with antiangiogenic, anti-inflammatory, and
      immunomodulatory properties that was found to inhibit the production of tumor
      necrosis factor-alpha (TNF-alpha) in vitro. We studied single nucleotide
      polymorphisms at positions -308 and -238 of the TNF-alpha gene promoter and
      measured the corresponding TNF-alpha cytokine levels in 81 patients (pts) with
      refractory and relapsed multiple myeloma (MM) who were treated with Thal. In
      myeloma pts carrying the TNF-238A allele (n = 8), we found a correlation with
      higher pretreatment TNF-alpha levels in peripheral blood (P =.047). After Thal
      administration, this TNF-238A group had a prolonged 12-month progression-free and
      overall survival of 86% and 100% versus 44% and 84% (P =.003 and P =.07) in pts
      with the TNF-238G allele, respectively. These findings suggest that regulatory
      polymorphisms of the TNF-alpha gene can affect TNF-alpha production and predict
      the outcome after Thal therapy, particularly in those MM pts who are genetically
      defined as "high producers" of TNF-alpha.

PMID- 12200399
TI  - Adaptive mechanisms of intracellular calcium homeostasis in mammalian
      hibernators.
AB  - Intracellular Ca(2+) homeostasis is a prerequisite for a healthy cell life. While
      cells from some mammals may suffer dysregulation of intracellular Ca(2+) levels
      under certain deleterious and stressful conditions, including hypothermia and
      ischemia, cells from mammalian hibernators exhibit a remarkable ability to
      maintain a homeostatic intracellular Ca(2+) environment. Compared with cells from
      non-hibernators, hibernator cells are characterized by downregulation of the
      activity of Ca(2+) channels in the cell membrane, which helps to prevent
      excessive Ca(2+) entry. Concomitantly, sequestration of Ca(2+) by intracellular
      Ca(2+) stores, especially the sarcoplasmic/endoplasmic reticulum, is enhanced to
      keep the resting levels of intracellular Ca(2+) stable. An increase in stored
      Ca(2+) in heart cells during hibernation ensures that the levels of Ca(2+)
      messenger are sufficient for forceful cell contraction under conditions of
      hypothermia. Maintenance of Na(+) gradients, via Na(+)-Ca(2+) exchangers, is also
      important in the Ca(2+) homeostasis of hibernator cells. Understanding the
      adaptive mechanisms of Ca(2+) regulation in hibernating mammals may suggest new
      strategies to protect nonhibernator cells, including those of humans, from Ca(2+)
      induced dysfunction.

PMID- 12200400
TI  - Design, limitations and sustained metabolic rate: lessons from small mammals.
AB  - Physiological limitations affect an organism's capacity to acquire and expend
      energy over long periods of activity. These limitations could be related to the
      central machinery used for acquiring, processing and allocating energy, or by the
      energy-consuming machinery. Another possibility is that the capacities of central
      and peripheral organs and tissues are co-adjusted, implying an optimized design.
      Given the important consequences that rates of energy expenditure have on many
      ecological aspects of animal life, we need to understand which factors impose
      ceilings on sustained metabolic rate. Ceilings on sustainable energy expenditure
      represent the limit below which all the activities performed by an individual
      must occur. There have been many studies of design constraints on energy budgets,
      but the different procedures used to identify the type of physiological
      limitation do not necessarily resolve which factors actually impose metabolic
      ceilings in small mammals, which precludes a clear understanding of the
      ecological and evolutionary consequences of design constraints on energy budgets.
      We propose that the following steps are necessary to identify the physiological
      limits on sustained metabolic rate: (1) combining peak energy demands to
      differentiate a central limitation from a peripheral limitation; (2) pushing the
      animals to their physiological limits (e.g. asymptotic food intake); (3) testing
      for a central excess capacity (if the limit is set peripherally), or a peripheral
      excess capacity (if there is a central limitation); (4) utilizing different
      levels of energy demand to test for symmorphosis.

PMID- 12200401
TI  - The role of Ca(2+) in stimulated bioluminescence of the dinoflagellate
      Lingulodinium polyedrum.
AB  - Many marine dinoflagellates emit bright discrete flashes of light nearly
      instantaneously in response to either laminar or turbulent flows as well as to
      direct mechanical stimulation. The flash involves a unique pH-dependent
      luciferase and a proton-mediated action potential across the vacuole membrane.
      The mechanotransduction process initiating this action potential is unknown. The
      present study investigated the role of Ca(2+) in the mechanotransduction process
      regulating bioluminescence in the dinoflagellate Lingulodinium polyedrum. Calcium
      ionophores and digitonin stimulated luminescence in a Ca(2+)-dependent manner in
      the absence of mechanical stimulation. Mechanically sensitive luminescence was
      strongly inhibited by the intracellular Ca(2+) chelator BAPTA-AM [1,2-bis(o
      aminophenoxy)ethane-N,N,N',N'- tetraacetic acid acetoxymethyl ester]; there was
      only a partial and irreversible dependence on extracellular Ca(2+). Ruthenium
      Red, a blocker of intracellular Ca(2+) release channels, inhibited mechanically
      sensitive luminescence. Luminescence was also stimulated by increasing K(+), even
      in the absence of extracellular Ca(2+); K(+) stimulation was inhibited both by
      BAPTA-AM and Ruthenium Red. These results support the hypothesis that Ca(2+)
      mediates stimulated bioluminescence and also indicate the involvement of
      intracellular Ca(2+) stores. Rapid coupling between mechanical stimulation and
      mobilization of intracellular Ca(2+) stores might occur through a mechanism
      similar to excitation-contraction coupling in skeletal muscle.

PMID- 12200402
TI  - The structural basis for water exchange between the female cockroach (Blattella
      germanica) and her ootheca.
AB  - Female German cockroaches usually carry their oothecae until they hatch. The
      success of embryogenesis may be dependent on the water-balance relationship
      between females and their developing oothecae. Oothecae detached from females
      early in embryogenesis often fail to develop, especially in low-humidity
      environments. Experiments reported here using tritiated water have confirmed the
      transport of a significant amount of water to the ootheca from the female during
      embryogenesis; 18% of the tritiated water injected into gravid females was
      recovered in their oothecae after 24 h. We describe a structural basis of water
      absorption by the oothecae. An area located on the proximal end of the ootheca
      (adjacent to the 'escutcheon-shaped vaginal imprint') contains small pores that
      penetrate the oothecal covering to access regions of the chorion lying beneath
      these pores. Experiments using microparabiotic chambers to examine transport of
      tritiated water and water-soluble materials across the escutcheon region of the
      oothecal covering, along with dark-field birefringent microscopy of the chorion,
      support the hypothesis that this chorionic network is capable of conducting water
      throughout the interior of the ootheca. Furthermore, the structural arrangement
      and intimate association of the female vestibulum with the oothecal pore field
      contained in the region of the escutcheon-shaped vaginal imprint appear to
      provide an efficient conduit to the chorion. The overall structural relationship
      might be a means for maintaining water balance between females and their oothecae
      during embryonic development. Evidence presented here supports observations that
      this species represents an important link in the transition from oviparity to
      ovoviviparity by internalization of cockroach oothecae.

PMID- 12200403
TI  - Fluid dynamics of flapping aquatic flight in the bird wrasse: three-dimensional
      unsteady computations with fin deformation.
AB  - Many fishes that swim with the paired pectoral fins use fin-stroke parameters
      that produce thrust force from lift in a mechanism of underwater flight. These
      locomotor mechanisms are of interest to behavioral biologists, biomechanics
      researchers and engineers. In the present study, we performed the first three
      dimensional unsteady computations of fish swimming with oscillating and deforming
      fins. The objective of these computations was to investigate the fluid dynamics
      of force production associated with the flapping aquatic flight of the bird
      wrasse Gomphosus varius. For this computational work, we used the geometry of the
      wrasse and its pectoral fin, and previously measured fin kinematics, as the
      starting points for computational investigation of three-dimensional (3-D)
      unsteady fluid dynamics. We performed a 3-D steady computation and a complete set
      of 3-D quasisteady computations for a range of pectoral fin positions and surface
      velocities. An unstructured, grid-based, unsteady Navier-Stokes solver with
      automatic adaptive remeshing was then used to compute the unsteady flow about the
      wrasse through several complete cycles of pectoral fin oscillation. The shape
      deformation of the pectoral fin throughout the oscillation was taken from the
      experimental kinematics. The pressure distribution on the body of the bird wrasse
      and its pectoral fins was computed and integrated to give body and fin forces
      which were decomposed into lift and thrust. The velocity field variation on the
      surface of the wrasse body, on the pectoral fins and in the near-wake was
      computed throughout the swimming cycle. We compared our computational results for
      the steady, quasi-steady and unsteady cases with the experimental data on axial
      and vertical acceleration obtained from the pectoral fin kinematics experiments.
      These comparisons show that steady state computations are incapable of describing
      the fluid dynamics of flapping fins. Quasi-steady state computations, with
      correct incorporation of the experimental kinematics, are useful when determining
      trends in force production, but do not provide accurate estimates of the
      magnitudes of the forces produced. By contrast, unsteady computations about the
      deforming pectoral fins using experimentally measured fin kinematics were found
      to give excellent agreement, both in the time history of force production
      throughout the flapping strokes and in the magnitudes of the generated forces.

PMID- 12200404
TI  - Amino acid composition and nutritional quality of potato leaf phloem sap for
      aphids.
AB  - To define plant 'nutritional quality' for aphids, the causal basis of the
      variation in aphid performance between host plants of different developmental
      ages was explored using the aphids Myzus persicae and Macrosiphum euphorbiae on
      potato plants (Solanum tuberosum). Both aphid species performed better on
      developmentally young ('pre-tuber-filling') plants than on mature ('tuber
      filling') plants. Aphid performance did not vary with leaf phloem sucrose:amino
      acid ratio but could be related to changes in the amino acid composition of the
      phloem, which included a developmental shift from high glutamine levels in pre
      tuber-filling plants to low glutamine levels in tuber-filling plants. Aphid
      performance on chemically defined 'young' and 'old' diets, with amino acid
      composition corresponding to that of phloem amino acid composition in pre-tuber
      filling and tuber-filling plants, respectively, confirmed that phloem amino acid
      composition contributed to low aphid performance on tuber-filling plants. The
      relatively poor performance on 'old' diets could be accounted for, at least in
      part, by depressed feeding rates. These data suggest that amino acid composition
      of the phloem is one factor shaping the nutritional quality of plants for aphids.

PMID- 12200405
TI  - Postnatal ecdysis establishes the permeability barrier in snake skin: new
      insights into barrier lipid structures.
AB  - A competent barrier to transepidermal water loss (TEWL) is essential for
      terrestrial life. In various vertebrates, epidermal water barriers composed of
      lipids prevent excessive TEWL, which varies inversely with habitat aridity.
      Little is known, however, about the mechanisms and regulation of permeability
      relative to natal transition from the 'aqueous' environments of gestation to the
      'aerial' environments of terrestrial neonates. We investigated newly hatched
      California king snakes Lampropeltis getula to test the hypothesis that the first
      ecdysis is important for establishing the barrier to TEWL. We found that skin
      resistance to TEWL increases twofold following the first postnatal ecdysis,
      corresponding with a roughly twofold increase in thickness and deposition of
      lamellar lipids in the mesos layer, the site of the skin permeability barrier in
      snakes. In addition, novel observations on lipid inclusions within the alpha
      layer of epidermis suggest that this layer has functional similarities with avian
      epidermis. It appears that emergence of the integument from embryonic fluids, and
      its subsequent pan-body replacement following contact with air, are essential for
      completion of barrier competence in the newborn. These conditions provide a
      potentially useful model for investigations on the mechanism of barrier
      formation. We also found that hatchling snakes are transiently endothermic, with
      skin temperatures elevated by approximately 0.6 degrees C above ambient air
      temperature during the period of barrier formation. Behaviourally, hatchlings
      showed a higher tendency to seek humid microenvironments before the first ecdysis
      than after. The degree of water movement across the integument might explain the
      switch from reclusive to dispersive behaviours associated with postnatal ecdysis
      in snakes.

PMID- 12200406
TI  - Magnetite-based magnetoreception in birds: the effect of a biasing field and a
      pulse on migratory behavior.
AB  - To test the hypothesis that single domain magnetite is involved in
      magnetoreception, we treated Australian silvereyes Zosterops l. lateralis with a
      strong, brief pulse designed to alter the magnetization of single domain
      particles. This pulse was administered in the presence of a 1 mT biasing field,
      either parallel to the direction of the biasing field (PAR group) or antiparallel
      (ANTI group). In the case of magnetoreceptors based on freely moving single
      domain particles, the PAR treatment should have little effect, whereas the ANTI
      treatment should cause remagnetization of the magnetite particles involved in a
      receptor and could produce a maximum change in that receptor's output for some
      receptor configurations. Migratory orientation was used as a criterion to assess
      the effect on the receptor. Before treatment, both groups preferred their normal
      northerly migratory direction. Exposure to the biasing field alone did not affect
      their behavior. Treatment with the pulse in the presence of the biasing field
      caused both the PAR and the ANTI birds to show an axial preference for the east
      west axis, with no difference between the two groups. Although these results are
      in accordance with magnetite-based magnetoreceptors playing a role in migratory
      orientation, they do not support the hypothesis that single domains in polarity
      sensitive receptors are free to move through all solid angles. Possible
      interpretations, including other arrangements of single domains and
      superparamagnetic crystals, are discussed.

PMID- 12200407
TI  - Mechanisms of ion transport in Potamotrygon, a stenohaline freshwater
      elasmobranch native to the ion-poor blackwaters of the Rio Negro.
AB  - Stingrays of the family Potamotrygonidae are the only stenohaline freshwater
      elasmobranchs. Potomotrygon sp. collected from the ion-poor blackwaters ([Na(+)],
      [Cl(-)] and [Ca(2+)]=10-30 micro mol l(-1), pH 6.1) of the Rio Negro, Amazonas,
      Brazil, were ammoniotelic (91% ammonia-N, 9% urea-N excretion) and exhibited
      blood chemistry (Na(+), Cl(-), urea, ammonia and glucose levels and osmolality)
      typical of freshwater teleosts. Unidirectional Na(+) and Cl(-) influx rates,
      measured with radiotracers, displayed saturation kinetics. The relationships for
      Cl(-) and Na(+) had similar K(m) values (300-500 micro mol l(-1)), but J(max)
      values for Cl(-) (approximately 950 micro mol kg(-1) h(-1)) were almost twice
      those for Na(+) (approximately 500 micro mol kg(-1) h(-1)). Cl(-) efflux rates
      varied with external concentration, but Na(+) efflux rates did not. There were no
      differences in the kinetic variables (K(m), J(max)) for influx between animals
      acclimated to their native ion-poor blackwater or to ion-rich hard water, but
      efflux rates for both Na(+) and Cl(-) were lower in the former, yielding much
      lower balance points (external Na(+) or Cl(-) levels at which influx and efflux
      were equal). Na(+), Cl(-) and Ca(2+) uptake were all strongly inhibited by acute
      exposure to pH 4.0, but efflux rates and Ca(2+) binding to the body surface did
      not change. Na(+) influx was inhibited by amiloride (10(-4) mol l(-1)) and by two
      of its analogs, phenamil (4 x 10(-5) mol l(-1)) and HMA (4 x 10(-5) mol l(-1)),
      with the latter being slightly more potent, while Cl(-) fluxes were unaffected.
      Cl(-) fluxes were insensitive to DIDS (2 x 10(-5) mol l(-1) or 10(-4) mol l(-1))
      and SITS (10(-4) mol l(-1)), but both influx and efflux rates were strongly
      inhibited by DPC (10(-4) mol l(-1)) and thiocyanate (10(-4) mol l(-1)). Ammonia
      excretion was unresponsive to large changes in water Na(+) concentration, but was
      elevated by 70% during acute exposure to pH 4.0 and transiently inhibited by
      approximately 50% by amiloride and its analogues. The strategy of adaptation to
      ion-poor blackwater appears similar to that of some Rio Negro teleosts
      (Cichlidae) in which low-affinity transport systems are relatively sensitive to
      inhibition by low pH but are complemented by low diffusive loss rates. Ionic
      transport systems in these freshwater elasmobranchs, although superficially
      similar to those in some freshwater teleosts, may bear more resemblance to their
      presumed evolutionary precursors in marine elasmobranchs.

PMID- 12200409
TI  - Serotonergic modulation of nonspiking local interneurones in the terminal
      abdominal ganglion of the crayfish.
AB  - The modulatory effect of serotonin on local circuit neurones forming the uropod
      motor control system of the crayfish Procambarus clarkii Girard was analysed
      electrophysiologically. Bath application of 10 micro mol l(-1) serotonin caused a
      decrease in the tonic spike activity of the exopodite reductor motor neurone. The
      inhibitory effect of serotonin on the motor neurone was dose-dependent and its
      spike discharge was completely suppressed for long periods by 1 mmol l(-1)
      serotonin perfusion. Nonspiking local interneurones in the terminal abdominal
      ganglion showed either a membrane depolarization (N=6) or hyperpolarization (N=9)
      of 10-30 mV in amplitude when 100 micro mol l(-1) serotonin was perfused for 3-5
      min. By contrast, spiking local interneurones and intersegmental ascending
      interneurones showed no observable excitatory responses to the perfusion of
      serotonin but instead some showed a small membrane hyperpolarization of 2-5 mV.
      These results indicate that the nonspiking interneurones could contribute
      substantially to the level of tonic excitation of the uropod motor neurones.
      Sensory stimulation elicited depolarizing or hyperpolarizing potentials in the
      nonspiking interneurones and excitatory postsynaptic potentials (EPSPs) and
      spikes in the spiking interneurones. The sensory responses of spiking
      interneurones increased during bath application of serotonin and were reduced
      after 20-30 min of washing with normal saline. In the nonspiking interneurones,
      the amplitude of both depolarizing and hyperpolarizing potentials increased
      without any direct correlation with the serotonin-mediated potential change. This
      effect of serotonin was long-lasting and continued to enhance the responses of
      the nonspiking interneurones after washing. This postserotonin enhancement
      persisted for over 1 h.

PMID- 12200408
TI  - Effects of metabolite uptake on proton-equivalent elimination by two species of
      deep-sea vestimentiferan tubeworm, Riftia pachyptila and Lamellibrachia cf
      luymesi: proton elimination is a necessary adaptation to sulfide-oxidizing
      chemoautotrophic symbionts.
AB  - Intracellular symbiosis requires that the host satisfy the symbiont's metabolic
      requirements, including the elimination of waste products. The hydrothermal vent
      tubeworm Riftia pachyptila and the hydrocarbon seep worm Lamellibrachia cf
      luymesi are symbiotic with chemolithoautotrophic bacteria that produce sulfate
      and protons as end-products. In this report, we examine the relationship between
      symbiont metabolism and host proton equivalent elimination in R. pachyptila and
      L. cf luymesi, and the effects of sulfide exposure on proton-equivalent
      elimination by Urechis caupo, an echiuran worm that lacks intracellular symbionts
      (for brevity, we will hereafter refer to proton-equivalent elimination as 'proton
      elimination'). Proton elimination by R. pachyptila and L. cf luymesi constitutes
      the worms' largest mass-specific metabolite flux, and R. pachyptila proton
      elimination is, to our knowledge, the most rapid reported for any metazoan.
      Proton elimination rates by R. pachyptila and L. cf luymesi correlated primarily
      with the rate of sulfide oxidation. Prolonged exposure to low environmental
      oxygen concentrations completely inhibited the majority of proton elimination by
      R. pachyptila, demonstrating that proton elimination does not result primarily
      from anaerobic metabolism. Large and rapid increases in environmental inorganic
      carbon concentrations led to short-lived proton elimination by R. pachyptila, as
      a result of the equilibration between internal and external inorganic carbon
      pools. U. caupo consistently exhibited proton elimination rates 5-20 times lower
      than those of L. cf luymesi and R. pachyptila upon exposure to sulfide. Treatment
      with specific ATPase inhibitors completely inhibited a fraction of proton
      elimination and sulfide and inorganic carbon uptake by R. pachyptila, suggesting
      that proton elimination occurs in large part via K(+)/H(+)-ATPases and Na(+)/H(+)
      ATPases. In the light of these results, we suggest that protons are the primary
      waste product of the symbioses of R. pachyptila and L. cf luymesi, and that
      proton elimination is driven by symbiont metabolism, and may be the largest
      energetic cost incurred by the worms.

PMID- 12200410
TI  - Low-temperature protein metabolism: seasonal changes in protein synthesis and RNA
      dynamics in the Antarctic limpet Nacella concinna Strebel 1908.
AB  - Protein synthesis is a fundamental and energetically expensive physiological
      process in all living organisms. Very few studies have examined the specific
      challenges of manufacturing proteins at low ambient temperatures. At high
      southern latitudes, water temperatures are continually below or near freezing and
      are highly stable, while food availability is very seasonal. To examine the
      effects of low temperature and a highly seasonal food supply on protein
      metabolism, we have measured wholebody protein synthesis, RNA concentrations,
      RNA:protein ratios and RNA translational efficiencies in the Antarctic limpet
      Nacella concinna at four times of the year. From summer to winter, protein
      synthesis rates decreased by 52%, RNA concentrations decreased by 55% and
      RNA:protein ratios decreased by 68%, while RNA translational efficiencies were
      low and very variable. Protein synthesis rates in N. concinna approached those
      measured in temperate mussels, while RNA:protein ratios were considerably higher
      than in temperate species. Interspecific comparisons show that species living at
      low temperatures have elevated RNA:protein ratios, which are probably needed to
      counteract a thermally induced reduction in RNA translational efficiency.
      Calculations using theoretical energetic costs of protein synthesis suggest that
      Antarctic species may allocate a larger proportion of their metabolic budget to
      protein synthesis than do temperate or tropical species.

PMID- 12200411
TI  - Response of western diamondback rattlesnakes Crotalus atrox to airborne sounds.
AB  - In order to test the hypothesis that snakes can not only perceive airborne
      sounds, but also respond to them, an acoustic isolation chamber was designed and
      constructed to perform best within the 150-450 Hz range in which snakes perceive
      sound. Suspended within this acoustic chamber was a steel mesh basket designed to
      minimize the potential for groundborne vibrations. A synthesized tone was created
      out of 20 different 150 ms sounds, each separated by a 50 ms period of silence;
      the acoustic energy of each of the 20 sounds was concentrated between 200-400 Hz,
      and each sound included frequency modulation. The trial stimuli were presented to
      western diamondback rattlesnakes Crotalus atrox at a level 5-10 dB above their
      perception threshold. Four significant behavioural responses were observed upon
      stimulus presentation: cessation of body movements, reduction or cessation of
      tongue flicking, rapid jerks of the head and rattling. At least one significant
      behavioural response was observed in 92% of the behavioural trials. This study
      provides the first experimental evidence that snakes can respond behaviourally to
      airborne sounds.

PMID- 12200412
TI  - Nitric oxide regulation of the central aortae of the toad Bufo marinus occurs
      independently of the endothelium.
AB  - Nitric oxide (NO) signalling pathways were examined in the lateral aortae and
      dorsal aorta of the cane toad Bufo marinus. NADPH diaphorase histochemistry and
      nitric oxide synthase (NOS) immunohistochemistry found no evidence for
      endothelial NOS in the endothelium of toad aortae, but it could be readily
      demonstrated in rat aorta that was used as a control. Immunohistochemistry using
      a specific neural NOS antibody showed the presence of neural NOS immunoreactivity
      in the perivascular nerves of the aortae. The anatomical data was supported by in
      vitro organ bath physiology, which demonstrated that the vasodilation mediated by
      applied acetylcholine (10(-5) mol l(-1)) was not dependent on the presence of the
      vascular endothelium; however, it was significantly reduced in the presence of a
      neural NOS inhibitor, vinyl-L-NIO (10(-4) mol l(-1)). In addition, atropine (10(
      6) mol l(-1)) (a muscarinic receptor inhibitor), L-NNA (10(-4) mol l(-1)) (a NOS
      inhibitor) and ODQ (10(-5) mol l(-1)) (an inhibitor of soluble guanylyl cyclase)
      abolished the vasodilatory effect of applied acetylcholine. In conclusion, we
      propose that an endothelial NO system is absent in toad aortae and that NO
      generated by neural NOS in perivascular nerves mediates vasodilation.

PMID- 12200413
TI  - The effects of lipid location on non-invasive estimates of body composition using
      EM-SCAN technology.
AB  - We evaluated the effect of lipid location on body-composition estimation accuracy
      using electromagnetic scanning (EM-SCAN), a non-invasive [total body electrical
      conductivity (TOBEC)] method. Molds were constructed that simulated a 'general'
      small mammal, either 93% lean/7% lipid (control) or 82% lean/18% lipid (lipid
      location groups). In the 18% lipid molds, we varied the location of the fat;
      simulating all the fat in the head, tail or midsection or simulating homogenous
      distribution. Comparisons were made between the EM-SCAN output of each lipid
      location group, and multiple-regression techniques were performed to derive body
      composition estimation equations for both lipid mass (M(L)) and fat-free mass
      (M(FF)). Device output varied significantly for all lipid-location groups even
      though all groups contained 18% body fat, showing a lipid-location effect on
      device output. Calibration equations derived for each lipid-location condition
      estimated both M(L) and M(FF) accurately, but an independent equation was
      required for each lipid-location condition. In situations where species
      significantly vary body fat content and location, for example during hibernation
      or reproductive periods, we suggest deriving a calibration equation that is more
      representative of the actual body composition to improve M(L) and M(FF)
      estimation accuracy using non-invasive EM-SCAN methods.

PMID- 12200414
TI  - Calcium-dependent cleavage of endogenous wild-type huntingtin in primary cortical
      neurons.
AB  - Huntington's disease (HD) is caused by a polyglutamine expansion in the amino
      terminal region of huntingtin. Mutant huntingtin is proteolytically cleaved by
      caspases, generating amino-terminal aggregates that are toxic for cells. The
      addition of calpains to total brain homogenates also leads to cleavage of wild
      type huntingtin, indicating that proteolysis of mutant and wild-type huntingtin
      may play a role in HD. Here we report that endogenous wild-type huntingtin is
      promptly cleaved by calpains in primary neurons. Exposure of primary neurons to
      glutamate or 3-nitropropionic acid increases intracellular calcium concentration,
      leading to loss of intact full-length wild-type huntingtin. This cleavage could
      be prevented by calcium chelators and calpain inhibitors. Degradation of wild
      type huntingtin by calcium-dependent proteases thus occurs in HD neurons, leading
      to loss of wild-type huntingtin neuroprotective activity.

PMID- 12200415
TI  - Analysis of the molecular mechanisms of human estrogen receptors alpha and beta
      reveals differential specificity in target promoter regulation by xenoestrogens.
AB  - Most of the currently available information on the transcriptional activities of
      endocrine-disrupting chemicals (xenoestrogens) through estrogen receptors alpha
      (ERalpha) and beta (ERbeta) has been derived from transactivation studies on
      synthetic estrogen-responsive reporters. Thus, the ability of the xenoestrogen
      liganded ERs to regulate endogenous estrogen-responsive gene expression has not
      been well characterized. Here, we have evaluated the activities of xenoestrogens
      through ERalpha and ERbeta on the vitellogenin A2 estrogen-response element (ERE)
      and the human pS2, lactoferrin, and complement 3 physiological target gene
      promoters. Using mammalian cell transient transfection assays, we found that the
      activities of xenoestrogens were mediated in a promoter-specific manner. For
      example, when bound to all ligands examined, ERalpha displayed high levels of
      transcription on the vitellogenin ERE and the lactoferrin promoter, but
      substantially lower activity on the complement 3 and pS2 promoters. However, one
      of the most important observations was that there were significant differences in
      the relative transcriptional activities of xenoestrogen-bound ERalpha and ERbeta
      on different promoters, suggesting that ERalpha and ERbeta make unique
      contributions to xenoestrogen action in target cells. When probing the molecular
      mechanism of the promoter-specific activities observed, we found that the
      transcriptional activity of the ERs correlated with the ability of each receptor
      to assume an active conformation on specific promoters. Taken together, the
      results indicate that the transcriptional activities of xenoestrogens are
      mediated in a promoter-specific manner and that estrogen-responsive promoters
      communicate differently with ERalpha and ERbeta by influencing their structures
      in a distinct manner that leads to diversity in their transcriptional responses.

PMID- 12200416
TI  - Glucose-dependent regulation of cholesterol ester metabolism in macrophages by
      insulin and leptin.
AB  - Insulin resistance, obesity, and diabetes are characterized by hyperglycemia,
      hyperinsulinemia, and hyperleptinemia and are associated with increased risk of
      atherosclerosis. In an effort to understand how this occurs, we have investigated
      whether these factors cause disregulation of cholesterol ester metabolism in
      J774.2 macrophages. Raising glucose levels alone was sufficient to increase
      uptake of acetylated low density lipoprotein but did not stimulate synthesis of
      cholesterol esters. In the presence of high glucose, both insulin and leptin
      increased the rate of cholesterol ester synthesis, although they did not further
      increase uptake of acetylated low density lipoprotein. However, in the presence
      of high glucose both insulin and leptin caused a significant increase in the
      activity of acyl-CoA: cholesterol O-acyltransferase (ACAT) combined with a
      significant reduction in the level of hormone-sensitive lipase (HSL). Because
      ACAT is the main enzyme responsible for cholesterol ester synthesis and HSL
      contributes significantly to neutral cholesterol ester hydrolase activity, this
      suggests that glucose primes the J774.2 cells so that in the presence of high
      insulin or leptin they will store cholesterol esters. This contrasts with 3T3-L1
      adipocytes, where HSL activity and expression are increased by insulin in high
      glucose conditions. These findings may provide an explanation for the observation
      that in conditions characterized by hyperglycemia, hyperleptinemia, and
      hyperinsulinemia, triglyceride lipolysis in adipocytes is increased while
      hydrolysis of cholesterol esters in macrophages is decreased, contributing to
      foam cell formation.

PMID- 12200417
TI  - General regulatory factors (GRFs) as genome partitioners.
AB  - Insulators are sequences that uncouple adjacent chromosome domains. Here we have
      shown that Saccharomyces cerevisiae Rap1p and Abf1p proteins are endowed with a
      potent insulating capacity. Insulating domains in Rap1p coincide with previously
      described transcription activation domains, whereas four adjacent subdomains
      spanning the whole of the Abf1p C terminus (440-731) were found to display
      autonomous insulating capacity. That both Rap1p and Abf1p silencing domains
      either contain or largely overlap with an insulating domain suggests that
      insulation conveys some undefined chromosome organization capacity that also
      contributes a function in silencing. Together with Reb1p and Tbf1p, previously
      involved in the activity of Saccharomyces cerevisiae subtelomeric insulators,
      insulating potential emerges as a supplementary common property of General
      Regulatory Factors (GRFs). Thus GRFs, which bind to sites scattered throughout
      the genome within promoters, would not only play a key role in regulating gene
      expression but also partition the genome in functionally independent domains.

PMID- 12200418
TI  - Serum response factor activation by muscarinic receptors via RhoA. Novel pathway
      specific to M1 subtype involving calmodulin, calcineurin, and Pyk2.
AB  - The muscarinic cholinergic receptor (mAChR) subtypes share high sequence
      similarity except in their third intracellular loop and COOH terminus, domains
      thought to be involved in signal transduction. Subtypes M1, M3, and M5 couple
      mainly through Galpha(q/11), and M2 and M4 couple mainly through Galpha(i/o).
      Whether subtypes within each of these two groups differ in their signaling
      pathways remains to be resolved. This study focused on nuclear signaling pathways
      leading to activation of the transcription factor, serum response factor (SRF).
      Genes encoding M1, M2, and M3 were co-expressed in Jurkat T lymphocytes with a
      reporter gene driven by a mutant serum response element, SRE.L, which responds to
      SRF activation. We show that only M1 mAChR activated SRF through a pathway
      involving the small GTPase RhoA, with no response observed for M2 and M3.
      Transfection of GTPase-deficient Galpha subunits (GalphaQL; constitutively active
      form) demonstrated that SRF was activated by Galpha(13)QL but only marginally by
      Galpha(q)QL and Galpha(12)QL in Jurkat cells. Yet transfection of regulator of G
      protein-signaling protein, RGS2 and RGS4, which inhibit Galpha(q/11) activity,
      indicated that Galpha(q/11) and Ca(2+) mobilization were required for SRF
      activation by M1. Calmodulin inhibitors suppressed the M1 and the Galpha(13)QL
      pathways, acting both upstream and downstream of RhoA. However, calcineurin
      inhibitors and the tyrosine kinase inhibitor genistein selectively suppressed SRF
      activation by M1, but not by Galpha(13)QL, indicating the presence of separate
      pathways. The calmodulin-dependent tyrosine kinase Pyk2 was also activated by M1
      but not M3, and Pyk2 appears also to play a role in M1-SRF activation, as judged
      by experiments with two dominant-negative Pyk2 mutants. These results reveal a
      novel calmodulin-dependent RhoA-SRF signaling pathway unique to the M1 mAChR
      subtype.

PMID- 12200419
TI  - Identification by mutagenesis of a conserved glutamate (Glu487) residue important
      for catalytic activity in rat liver carnitine palmitoyltransferase II.
AB  - Mammalian mitochondrial membranes express two active but distinct carnitine
      palmitoyltransferases: carnitine palmitoyltransferase I (CPTI), which is malonyl
      coA-sensitive and detergent-labile; and carnitine palmitoyltransferase II
      (CPTII), which is malonyl coA-insensitive and detergent-stable. To determine the
      role of the highly conserved C-terminal acidic residues glutamate 487 (Glu(487))
      and glutamate 500 (Glu(500)) on catalytic activity in rat liver CPTII, we
      separately mutated these residues to alanine, aspartate, or lysine, and the
      effect of the mutations on CPTII activity was determined in the Escherichia coli
      expressed mutants. Substitution of Glu(487) with alanine, aspartate, or lysine
      resulted in almost complete loss in CPTII activity. Because a conservative
      substitution mutation of this residue, Glu(487) with aspartate (E487D), resulted
      in a 97% loss in activity, we predicted that Glu(487) would be at the active-site
      pocket of CPTII. The substantial loss in CPTII activity observed with the E487K
      mutant, along with the previously reported loss in activity observed in a child
      with a CPTII deficiency disease, establishes that Glu(487) is crucial for
      maintaining the configuration of the liver isoform of the CPTII active site.
      Substitution of the conserved Glu(500) in CPTII with alanine or aspartate reduced
      the V(max) for both substrates, suggesting that Glu(500) may be important in
      stabilization of the enzyme-substrate complex. A conservative substitution of
      Glu(500) to aspartate resulted in a significant decrease in the V(max) for the
      substrates. Thus, Glu(500) may play a role in substrate binding and catalysis.
      Our site-directed mutagenesis studies demonstrate that Glu(487) in the liver
      isoform of CPTII is essential for catalysis.

PMID- 12200420
TI  - Novel function of the transactivation domain of a pituitary-specific
      transcription factor, Pit-1.
AB  - Pit-1 stimulates the expression of growth hormone, prolactin, and thyrotropin
      beta subunit genes. Consequently, abnormality of the Pit-1 gene results in
      combined pituitary hormone deficiency (CPHD). In this study, we analyzed the
      function of Pit-1 with a mutation (proline to leucine at codon 24) in the
      transactivation domain, P24L, which has a normal POU domain important for binding
      to DNA, because this mutation had been reported in a patient with CPHD. We found
      that codon 24 proline in the transactivation domain as well as the POU domain of
      Pit-1 was crucial to recruit coactivator CREB-binding protein (CBP) in the
      cultured cells. P24L completely lost the responsiveness to cAMP to stimulate the
      expression of the Pit-1-targeted genes. Furthermore, CBP and Pit-1, but not P24L,
      markedly enhanced the expression of the Pit-1-targeted gene to cAMP, and
      adenovirus E1a that binds to CBP and abrogates its function blocked the induction
      by cAMP of Pit-1-stimulated gene transcription in the pituitary-derived GH3
      cells. These results suggest that CBP and proline at codon 24 in the
      transactivation domain of Pit-1 are important for the cAMP-induced activation of
      Pit-1-targeted genes. However, P24L maintained basal transcriptional activity,
      suggesting that CBP is unlikely to be an essential coactivator for Pit-1.

PMID- 12200421
TI  - The BmE75 nuclear receptors function as dominant repressors of the nuclear
      receptor BmHR3A.
AB  - The orphan nuclear receptors BmE75 and BmHR3 are induced by 20-hydroxyecdysone in
      the ovary of the silk moth Bombyx mori at the beginning of pupation and show
      stage-specific expression in ovarian follicles during pharate adult development.
      To analyze the function of these receptors, we have developed a transactivation
      assay based on the transcriptional stimulation of a retinoic acid receptor
      related receptor response element (RORE)-linked promoter-reporter construct. Co
      transfection of a Bombyx cell line with a BmHR3A expression construct results in
      constitutive activation of the reporter, whereas expression of BmE75 has no
      measurable effects on reporter expression. However, when the BmE75 receptors are
      co-introduced with BmHR3A into the cells, the BmHR3A-mediated transactivation is
      repressed. Repression of BmHR3A by BmE75 occurs by two distinct mechanisms.
      Increasing doses of BmE75 efficiently displace BmHR3A bound to the RORE target
      site in gel retardation assays, indicating that both receptors compete for common
      DNA target sites. However, analysis of the function of deletion mutants of BmE75
      in the transactivation assay indicates that repression can also occur in the
      absence of the DNA-binding domain and that the C-terminal F domain is sufficient
      for repression. In gel retardation assays, the two receptor types form a ternary
      complex on a single RORE, suggesting that repression is also mediated by protein
      interactions on the DNA target site. Yeast two-hybrid assays show that BmHR3A
      interacts with BmE75 and that this interaction is dependent on the C terminus of
      BmHR3A and the F domain of BmE75. Because the C terminus of BmHR3A contains a
      strong activation domain, we predict that BmE75 blocks activation by BmHR3A
      through competition for co-activator binding sites located at the C terminus of
      BmHR3A. Our data also indicate that the transcriptional activities of BmHR3A and
      BmE75 are integrated in such a way that activation of RORE-linked target genes
      depends on the relative expression levels of the two receptor types.

PMID- 12200422
TI  - Differential protein expression at the stage of neural tube closure in the mouse
      embryo.
AB  - Analysis of the protein complement of a biological system through proteomics
      provides the opportunity to directly monitor the functional readout of gene
      expression. In this study, proteomics was applied to the mouse embryo to
      investigate the molecular events underlying the processes occurring at the stage
      of neural tube closure. Protein profiles of embryos between embryonic days 8.5
      and 10.5 exhibited a number of stage-specific changes. Identification of
      developmentally regulated proteins by mass spectrometry revealed several groups
      of functionally related proteins including circulatory, cytoskeletal, and stress
      proteins. Additional proteins of unknown function were identified, such as Copine
      1 and PICOT, whose developmental regulation was previously unsuspected.

PMID- 12200423
TI  - ACTH-induced nucleocytoplasmic translocation of salt-inducible kinase.
      Implication in the protein kinase A-activated gene transcription in mouse
      adrenocortical tumor cells.
AB  - Salt-inducible kinase (SIK), a serine/threonine protein kinase expressed at an
      early stage of adrenocorticotropic hormone (ACTH) stimulation in Y1 mouse
      adrenocortical tumor cells, repressed the cAMP-responsive element (CRE)-dependent
      gene transcription by acting on the basic leucine zipper domain of the CRE
      binding protein (Doi, J., Takemori, H., Lin, X.-z., Horike, N., Katoh, Y., and
      Okamoto, M. (2002) J. Biol. Chem. 277, 15629-15637). The mechanism of SIK
      mediated gene regulation has been further explored. Here we show that SIK changes
      its subcellular location after the addition of ACTH. The immunocytochemical and
      fluorocytochemical analyses showed that SIK was present both in the nuclear and
      cytoplasmic compartments of resting cells; when the cells were stimulated with
      ACTH the nuclear SIK moved into the cytoplasm within 15 min; the level of SIK in
      the nuclear compartment gradually returned to the initial level after 12 h. SIK
      translocation was blocked by pretreatment with leptomycin B. A mutant SIK whose
      Ser-577, the cAMP-dependent protein kinase (PKA)-dependent phosphorylation site,
      was replaced with Ala could not move out of the nucleus under stimulation by
      ACTH. As expected, the degree of repression exerted by SIK on CRE reporter
      activity was weak as long as SIK was present in the cytoplasmic compartment. The
      same was true for the SIK-mediated repression of a steroidogenic acute regulatory
      (StAR) protein-gene promoter, which contained a CRE-like sequence at -95 to -85
      bp. These results suggest that in the ACTH-stimulated Y1 cells the nuclear SIK
      was PKA-dependently phosphorylated, and the phosphorylated SIK was then
      translocated out of the nuclei. This intracellular translocation of SIK, a CRE
      repressor, may account for the time-dependent change in the level of ACTH
      activated expression of the StAR protein gene.

PMID- 12200424
TI  - Cloning and characterization of GRIPE, a novel interacting partner of the
      transcription factor E12 in developing mouse forebrain.
AB  - The helix-loop-helix (HLH) family of transcription factors are key contributors
      to a wide array of developmental processes, including neurogenesis and
      hematopoiesis. These factors are thought to exert their regulatory influences by
      binding to cognate promoter-DNA sequences as dimers. Although studies in mice
      have convincingly demonstrated that neurogenic HLH proteins such as NeuroD are
      intimately involved in neuronal fate determination, the role of the ubiquitously
      expressed HLH protein, E12, in mammalian neurogenesis remains ambiguous. To
      address this, a yeast two-hybrid interaction screen was employed to identify
      dimerization partners to E12. Screening of an embryonic day 11.5 forebrain
      library resulted in the cloning of GRIPE, a novel GAP-related interacting protein
      to E12. GRIPE binds to the HLH region of E12 and may require E12 for nuclear
      import. Furthermore, GRIPE may negatively regulate E12-dependent target gene
      transcription. High levels of GRIPE and E12 mRNA were coincidentally detected
      during embryogenesis, but only GRIPE mRNA levels remained high in adult brain,
      particularly in neurons of the cortex and hippocampus. These observations were
      recapitulated through an in vitro model of neurogenesis. Taken together, these
      results indicate that GRIPE is a novel protein dimerization of which with E12 has
      important consequences for cells undergoing neuronal differentiation.

PMID- 12200425
TI  - Mechanism of superoxide and hydrogen peroxide formation by fumarate reductase,
      succinate dehydrogenase, and aspartate oxidase.
AB  - Oxidative stress is created in aerobic organisms when molecular oxygen chemically
      oxidizes redox enzymes, forming superoxide (O2*-) and hydrogen peroxide (H2O2).
      Prior work identified several flavoenzymes from Escherichia coli that tend to
      autoxidize. Of these, fumarate reductase (Frd) is notable both for its high
      turnover number and for its production of substantial O2*- in addition to H2O2.
      We have sought to identify characteristics of Frd that predispose it to this
      behavior. The ability of excess succinate to block autoxidation and the
      inhibitory effect of lowering the flavin potential indicate that all detectable
      autoxidation occurs from its FAD site, rather than from iron-sulfur clusters or
      bound quinones. The flavin adenine dinucleotide (FAD) moiety of Frd is unusually
      solvent-exposed, as evidenced by its ability to bind sulfite, and this may make
      it more likely to react adventitiously with O2*-. The autoxidizing species is
      apparently fully reduced flavin rather than flavosemiquinone, since treatments
      that more fully reduce the enzyme do not slow its turnover number. They do,
      however, switch the major product from O2*- to H2O2. A similar effect is achieved
      by lowering the potential of the proximal [2Fe-2S] cluster. These data suggest
      that Frd releases O2*- into bulk solution if this cluster is available to
      sequester the semiquinone electron; otherwise, that electron is rapidly
      transferred to the nascent superoxide, and H2O2 is the product that leaves the
      active site. This model is supported by the behavior of "aspartate oxidase"
      (aspartate:fumarate oxidoreductase), an Frd homologue that lacks Fe-S clusters.
      Its dihydroflavin also reacts avidly with oxygen, and H2O2 is the predominant
      product. In contrast, succinate dehydrogenase, with high potential clusters,
      generates O2*- exclusively. The identities of enzyme autoxidation products are
      significant because O2*- and H2O2 damage cells in different ways.

PMID- 12200426
TI  - Bid-mediated mitochondrial pathway is critical to ischemic neuronal apoptosis and
      focal cerebral ischemia.
AB  - We have investigated the role of the BH3-only pro-death Bcl-2 family protein,
      Bid, in ischemic neuronal death in a murine focal cerebral ischemia model. Wild
      type and bid-deficient mice of inbred C57BL/6 background were subjected to 90-min
      ischemia induced by left middle cerebral artery occlusion followed by 72-h
      reperfusion. The volume of ischemic infarct was significantly smaller in the bid
      deficient brains than in the wild-type brains, suggesting that Bid participated
      in the ischemic neuronal death. Indeed, following the ischemic treatment there
      was a significant reduction of apoptosis in the ischemic areas, particularly in
      the inner infarct border zone (the penumbra), of the bid-deficient brains. In
      addition, activation of Bid in the wild-type brains could be readily detected at
      approximately 3 h after ischemia, as evidenced by its proteolytic cleavage and
      translocation to the mitochondria as determined using Western blot analysis and
      immunofluorescence staining. Correspondingly, mitochondrial release of cytochrome
      c could be detected around the same time Bid was cleaved in the wild-type brains.
      However, no significant cytochrome c release was detected in the bid-deficient
      brains until 24 h later. This suggests that, although the mitochondrial apoptosis
      pathway might be activated by multiple mechanisms during focal cerebral ischemia,
      Bid is critical to its early activation. This notion was further supported by the
      finding that caspase-3 activation was severely impaired in the bid-deficient
      brains, whereas activation of caspase-8 was much less affected. Taken together,
      these data suggest that Bid is activated early in neuronal ischemia in a caspase
      8-dependent fashion and that Bid is perhaps one of the earliest and most potent
      activators of the mitochondrial apoptosis pathway. Thus, the role of Bid in the
      induction of ischemic neuronal death may render this molecule an attractive
      target for future therapeutic intervention.

PMID- 12200427
TI  - Action of complexin on SNARE complex.
AB  - Calcium-dependent synaptic vesicle exocytosis requires three SNARE (soluble N
      ethylmaleimide-sensitive-factor attachment protein receptor) proteins:
      synaptobrevin/vesicle-associated membrane protein in the vesicular membrane and
      syntaxin and SNAP-25 in the presynaptic membrane. The SNAREs form a
      thermodynamically stable complex that is believed to drive fusion of vesicular
      and presynaptic membranes. Complexin, also known as synaphin, is a neuronal
      cytosolic protein that acts as a positive regulator of synaptic vesicle
      exocytosis. Complexin binds selectively to the neuronal SNARE complex, but how
      this promotes exocytosis remains unknown. Here we used purified full-length and
      truncated SNARE proteins and a gel shift assay to show that the action of
      complexin on SNARE complex depends strictly on the transmembrane regions of
      syntaxin and synaptobrevin. By means of a preparative immunoaffinity procedure to
      achieve total extraction of SNARE complex from brain, we demonstrated that
      complexin is the only neuronal protein that tightly associates with it. Our data
      indicated that, in the presence of complexin, the neuronal SNARE proteins
      assemble directly into a complex in which the transmembrane regions interact. We
      propose that complexin facilitates neuronal exocytosis by promoting interaction
      between the complementary syntaxin and synaptobrevin transmembrane regions that
      reside in opposing membranes prior to fusion.

PMID- 12200428
TI  - CpG-binding protein is a nuclear matrix- and euchromatin-associated protein
      localized to nuclear speckles containing human trithorax. Identification of
      nuclear matrix targeting signals.
AB  - CpG-binding protein (CGBP) binds unmethylated CpG dinucleotides and is essential
      for mammalian development. CGBP exhibits a punctate nuclear localization
      correlated with 4,6-diamidino-2-phenylindole light regions and is excluded from
      metaphase chromosomes. The distribution of CGBP is distinct from the
      heterochromatin-associated proteins MBD1, methyl-CpG-binding protein 2, and
      HP1alpha. Some CGBP-containing nuclear speckles co-localize with splicing factor
      SC-35 and actively transcribed regions of the genome, whereas most CGBP co
      localizes with acetylated histones, indicating that CGBP is localized to active
      chromatin. CGBP contains two nuclear localization signals that are insufficient
      to direct punctate subnuclear distribution. Instead, localization of CGBP to
      nuclear speckles requires signals within the acidic, basic, and coiled-coil
      domains. CGBP associates with the nuclear matrix, and fragments of CGBP that fail
      to associate with the nuclear matrix fail to localize to nuclear speckles and
      exhibit reduced transcriptional activation activity. Mutated versions of CGBP
      that lack DNA binding activity exhibit a normal nuclear distribution, suggesting
      that CGBP accumulates at nuclear speckles as a result of protein/protein
      interactions. Importantly, the subcellular distribution of CGBP is identical to
      human trithorax, suggesting that these proteins may be components of a multimeric
      complex analogous to the histone-methylating Set1 complex of Saccharomyces
      cerevisiae that contains CGBP and trithorax homologues.

PMID- 12200429
TI  - Loricrin expression in cultured human keratinocytes is controlled by a complex
      interplay between transcription factors of the Sp1, CREB, AP1, and AP2 families.
AB  - The major protein component of the cornified cell envelope barrier structure of
      the epidermis is loricrin, and it is expressed late during terminal
      differentiation in epidermal keratinocytes. We have previously shown that an AP1
      site located in the proximal promoter region (position -55) is essential for
      human loricrin promoter activity (Rossi, A., Jang, S-I., Ceci, R., Steinert, P.
      M., and Markova, N. G. (1998) J. Invest. Dermatol. 110, 34-40). In this study we
      show that its regulation requires complex cooperative and competitive
      interactions between multiple transcription factors in keratinocytes located in
      different compartments of the epidermis. We show that as few as 154 base pairs of
      5'-upstream sequences from the cap site can direct the keratinocyte-specific
      expression in cultured keratinocytes. Mutation and DNA-protein analyses show that
      Sp1, c-Jun, an unidentified regulator, and the co-activator p300/CREB-binding
      protein up-regulate whereas Sp3, CREB-1/CREMalpha/ATF-1, Jun B, and an AP2-like
      protein (termed the keratinocyte-specific repressor-1 (KSR-1)) suppress loricrin
      promoter activity. We show that CREB protein can compete with c-Jun for the AP1
      site and repress loricrin promoter activity. We show here that the protein kinase
      A pathway can activate loricrin expression by manipulation of the Sp1, Sp3, and
      KSR-1 levels in the nucleus. Thus, in undifferentiated cells, loricrin expression
      is suppressed by Jun B, Sp3, and KSR-1 proteins. But in advanced differentiated
      cells, levels of Sp3, KSR-1, and CREB proteins are lower; the unidentified
      regulator protein can bind; Sp1 and c-Jun are increased; and then p300/CBP is
      recruited. Together, these events allow loricrin transcription to proceed.
      Indeed, the synergistic effects of the Sp1, c-Jun, and p300 factors indicate that
      p300/CBP might act as bridge to form an active transcription complex.

PMID- 12200430
TI  - Mcm3 is polyubiquitinated during mitosis before establishment of the pre
      replication complex.
AB  - To ensure fidelity in genome duplication, eukaryotes restrict DNA synthesis to
      once every cell division by a cascade of regulated steps. Central to this cascade
      is the periodic assembly of the hexameric MCM2-7 complex at replication origins.
      However, in Saccharomyces cerevisiae, only a fraction of each MCM protein is able
      to assemble into hexamers and associate with replication origins during M phase,
      suggesting that MCM complex assembly and recruitment may be regulated post
      translationally. Here we show that a small fraction of Mcm3p is polyubiquitinated
      at the onset of MCM complex assembly. Reducing the rate of ubiquitination by uba1
      165, a suppressor of mcm3-10, restored the interaction of Mcm3-10p with subunits
      of the MCM complex and its recruitment to the replication origin. Possible roles
      for ubiquitinated Mcm3p in the assembly of the MCM complex at replication origins
      are discussed.

PMID- 12200431
TI  - Largest subunits of the human SWI/SNF chromatin-remodeling complex promote
      transcriptional activation by steroid hormone receptors.
AB  - The mammalian SWI/SNF-related complexes facilitate gene transcription by
      remodeling chromatin using the energy of ATP hydrolysis. The recruitment of these
      complexes to promoters remains poorly understood and may involve histone
      modifications or direct interactions with site-specific transcription factors or
      other cofactors. Here we report the isolation of two related but distinct cDNA
      clones, hOsa1 and hOsa2, that encode the largest subunits of human SWI/SNF. hOsa1
      is identical to previously reported BAF250, and hOsa2 shares a high degree of
      sequence similarity with hOsa1. Mass spectrometric analysis, and immunoblotting
      with antibodies specific to hOsa1 or hOsa2 demonstrate the presence of both
      proteins in SWI/SNF-A but not in the related polybromo-BRG1-associated factors
      complex purified from HeLa cells. Co-precipitation studies indicate that hOsa1
      and hOsa2 associate with BRG1 and hBRM through the C-terminal domain of hOsa. We
      define multiple domains within hBRM and BRG1 that interact with the hOsa C
      terminus. In cultured mammalian cells, hOsa1 and hOsa2 stimulate transcription by
      the glucocorticoid, estrogen, and androgen receptors. The glucocorticoid receptor
      mediated activation is not observed with the C-terminal domain or with the hOsa2
      polypeptide lacking the ARID DNA binding domain. These results suggest that hOsa1
      and hOsa2 participate in promoting transcriptional activation by the steroid
      hormone receptors.

PMID- 12200432
TI  - The degree of oligomerization of the H-NS nucleoid structuring protein is related
      to specific binding to DNA.
AB  - At several E. coli promoters, initiation of transcription is repressed by a tight
      nucleoprotein complex formed by the assembly of the H-NS protein. In order to
      characterize the relationship between the structure of H-NS oligomers in solution
      and on relevant DNA fragments, we have compared wild-type H-NS and several
      transdominant H-NS mutants using gel shift assays, DNase I footprinting,
      analytical ultracentrifugation, and reactivity toward a cross-linking reagent. In
      solution, oligomerization occurs through two protein interfaces, one necessary to
      construct a dimeric core (and involving residues 1-64) and the other required for
      subsequent assembly of these dimers. We show that, as well as region 64-95,
      residues present in the NH(2)-terminal coiled coil domain also participate in
      this second interface. Our results support the view that the same interacting
      interfaces are also involved on the DNA. We propose that the dimeric core
      recognizes specific motifs, with the second interface being critical for their
      correct head to tail assembly. The COOH-terminal domain of the protein contains
      the DNA binding motif essential for the discrimination of this specific
      functional assembly over competitive nonspecific H-NS polymers.

PMID- 12200433
TI  - Activated pp60c-Src leads to elevated hypoxia-inducible factor (HIF)-1alpha
      expression under normoxia.
AB  - Hypoxia-inducible factor (HIF)-1 is a master transcription factor, which up
      regulates glycolysis, erythropoiesis, and angiogenesis under hypoxia. HIF-1alpha
      accumulates in normoxic tumor cells, leading to glycolysis under aerobic
      conditions. This phenomenon, known as the "Warburg effect," is caused by a yet
      unknown mechanism. Here we show that transformed cells that express
      constitutively active pp60(c-Src) (Src) express HIF-1alpha protein under
      normoxia, which results in the expression of multiple HIF-1alpha target genes. We
      show that this occurrence is due to an enhanced rate of HIF-1alpha protein
      synthesis and not due to reduced HIF-1alpha degradation. Furthermore, we show
      that the Src-induced increase in protein synthesis is due to the global increase
      in the rate of cap-dependent translation and does not involve inhibition of HIF
      1alpha degradation.

PMID- 12200434
TI  - Osteopontin transcription in aortic vascular smooth muscle cells is controlled by
      glucose-regulated upstream stimulatory factor and activator protein-1 activities.
AB  - The expression of the matrix cytokine osteopontin (OPN) is up-regulated in aortic
      vascular smooth muscle cells (VSMCs) by diabetes. OPN expression in cultured
      VSMCs is reciprocally regulated by glucose and 2-deoxyglucose (2-DG; inhibitor of
      cellular glucose metabolism). Systematic analyses of OPN promoter-luciferase
      reporter constructs identify a CCTCATGAC motif at nucleotides -80 to -72 relative
      to the initiation site that supports OPN transcription in VSMCs. The region -83
      to -45 encompassing this motif confers basal and glucose- and 2-DG-dependent
      transcription on an unresponsive promoter. Competition and gel mobility
      supershift assays identify upstream stimulatory factor (USF; USF1:USF2) and
      activator protein-1 (AP1; c-Fos:c-Jun) in complexes binding the composite
      CCTCATGAC element. Glucose up-regulates both AP1 and USF binding activities 2
      fold in A7r5 cells and selectively up-regulates USF1 protein levels. By contrast,
      USF (but not AP1) binding activity is suppressed by 2-DG and restored by glucose
      treatment. Expression of either USF or AP1 activates the proximal OPN promoter in
      A7r5 VSMCs in part via the CCTCATGAC element. Moreover, glucose stimulates the
      transactivation functions of c-Fos and USF1, but not c-Jun, in one-hybrid assays.
      Mannitol does not regulate binding, transactivation functions, USF1 protein
      accumulation, or OPN transcription. Thus, OPN gene transcription is regulated by
      USF and AP1 in aortic VSMCs, entrained to changes in cellular glucose metabolism.

PMID- 12200435
TI  - The human "prion-like" protein Doppel is expressed in both Sertoli cells and
      spermatozoa.
AB  - The prion-like Doppel protein (Dpl) has many biochemical and structural
      properties in common with the cellular prion protein (PrP(c)), and the
      physiological role of neither protein is known. Experimental data suggest either
      direct or indirect interaction between the two proteins. In this study, we
      investigated the expression pattern and biochemical characteristics of Dpl in
      human tissues and in Chinese hamster ovary cells transfected with wild-type or
      variant human Dpl gene constructs. Human Dpl appears to be a
      glycosylphosphatidylinositol-anchored glycoprotein with N- and O-linked sugars.
      It was found on Sertoli cells in the testis, on the flagella of epididymal and
      mature spermatozoa, and in seminal plasma. Dpl coexists only with N-terminally
      truncated isoforms of PrP(c) on mature spermatozoa. The localization of human Dpl
      on both Sertoli cells (somatic cells) and spermatozoa (germinal cells) strongly
      suggests that this protein may play a major role in human male fertility.
      Finally, our data indicate that spermatozoa are thus an interesting model for
      studies of the potential interaction between Dpl and PrP(c).

PMID- 12200436
TI  - Enhanced glycogen synthase kinase-3beta activity mediates hypoxia-induced
      apoptosis of vascular smooth muscle cells and is prevented by glucose transport
      and metabolism.
AB  - Hypoxia triggers apoptosis in a number of different cell types largely through a
      mitochondrial cell death pathway, which can be abrogated for the most part by
      enhanced glucose metabolism. The purpose of the current study was to identify
      intracellular signaling mechanisms that mediate hypoxia-induced apoptosis and are
      regulated by glucose metabolism. Hypoxia-induced apoptosis in vascular smooth
      muscle cells and COS-7 cells was accompanied by a significant reduction in Akt
      and glycogen synthase kinase-3 (GSK-3) phosphorylation resulting in increased GSK
      3 activity. Morphologic features of apoptosis, as well as caspases 3 and 9
      activation, were prevented by GSK-3 inhibition with either LiCl or SB216763.
      Phosphorylation of Akt and GSK-3 was enhanced by glucose metabolism or
      overexpression of the glucose transporter, GLUT1, and was prevented by glycolytic
      inhibition. These findings indicate that GSK-3 is an important mediator of
      hypoxia-induced apoptosis and that GSK-3-mediated apoptotic effects occur via
      activation of the mitochondrial death pathway. Moreover, the results suggest that
      prevention of hypoxia-mediated apoptosis by enhanced glucose transport and
      metabolism results, in part, from inhibition of GSK-3 activation.

PMID- 12200437
TI  - Mitochondrial Hsp60, resistance to oxidative stress, and the labile iron pool are
      closely connected in Saccharomyces cerevisiae.
AB  - In the present study, we have analyzed the role of the molecular chaperone Hsp60
      in protection of Saccharomyces cerevisiae against oxidative damage. We
      constructed mutant strains in which the levels of Hsp60 protein, compared with
      wild-type cells, were four times greater, and the addition of doxycycline
      gradually reduces them to 20% of wild-type. Under oxidative-stress conditions,
      the progressive decrease in Hsp60 levels in these mutants resulted in reduced
      cell viability and an increase in both cell peroxide species and protein carbonyl
      content. Protection of Fe/S-containing enzymes from oxidative inactivation was
      found to be dose-dependent with respect to Hsp60 levels. As these enzymes release
      their iron ions under oxidative-stress conditions, the intracellular labile iron
      pool, monitored with calcein, was higher in cells with reduced Hsp60 levels.
      Consistently, the iron chelator deferoxamine protected low Hsp60-expressing cells
      from both oxidant-induced death and protein oxidation. These results indicate
      that the role of Hsp60 in oxidative-stress defense is explained by protection of
      several Fe/S proteins, which prevent the release of iron ions and thereby avert
      further damage.

PMID- 12200438
TI  - Cessation of growth to prevent cell death due to inhibition of
      phosphatidylcholine synthesis is impaired at 37 degrees C in Saccharomyces
      cerevisiae.
AB  - Phosphatidylcholine is the most abundant phospholipid in eukaryotic cells,
      comprising 50% of total cellular phospholipid, and thus plays a major role in
      cellular and organellar biogenesis. In this study, we have used both nutritional
      deprivation as well as a conditional temperature sensitive allele of PCT1
      (CTP:phosphocholine cytidylyltransferase) coupled with an inactivated
      phosphatidylethanolamine methylation pathway to determine how cells respond to
      inactivation of phosphatidylcholine synthesis. Metabolic studies determined that
      phosphatidylcholine biosynthesis decreased to negligible levels within 1 h upon
      shift to the nonpermissive temperature for the temperature-sensitive PCT1 allele.
      Phosphatidylcholine mass decreased to negligible levels upon removal of choline
      from the medium or growth at the nonpermissive temperature, with the levels of
      the other major phospholipids increasing slightly. Cell growth rate visibly
      slowed upon cessation of phosphatidylcholine synthesis. Cells remained viable for
      7-8 h after phosphatidylcholine synthesis was prevented; however, at time points
      beyond 8 h, viability was significantly reduced but only if the cells had been
      previously grown at 37 degrees C and not 25 degrees C. The inhibition of
      phosphatidylcholine synthesis at 37 degrees C did not alter Golgi-derived vesicle
      transport to the vacuole as monitored by carboxypeptidase Y processing or to the
      plasma membrane as determined by invertase secretion. Immunofluorescence
      microscopy localized Pct1p to the nucleus and nuclear membrane. Pct1p activity is
      regulated by Sec14p, a cytoplasm/Golgi localized
      phosphatidylcholine/phosphatidylinositol binding protein that regulates Golgi
      derived vesicle transport partially through its ligand-dependent regulation of
      PCT1 derived enzyme activity. Our nuclear localization of Pct1p indicates that
      the regulation of Pct1p by Sec14p is indirect.

PMID- 12200439
TI  - Cohesin defects lead to premature sister chromatid separation, kinetochore
      dysfunction, and spindle-assembly checkpoint activation.
AB  - Scc1/Mcd1 is a component of the cohesin complex that plays an essential role in
      sister chromatid cohesion in eukaryote cells. Knockout experiments of this gene
      have been described in budding yeast, fission yeast, and chicken cells, but no
      study has been reported on human Scc1 thus far. In this study, we found that an N
      terminally truncated human Scc1 shows a dominant-negative effect, and we examined
      the phenotypes of human cells defective in Scc1 function. Scc1 defects led to
      failure of sister chromatid cohesion in both interphase and mitotic cells.
      Interestingly, four chromatids derived from two homologues occupied four distinct
      territories in the nucleus in chromosome painting experiments. In mitotic Scc1
      defective cells, chromatids were disjoined with normal condensation, and the
      spindle-assembly checkpoint was activated. We also found that, although the
      disjoined kinetochore (half-kinetochore) in Scc1-defective cells contains CENP-A,
      -B, -C, and -E normally, it apparently does not establish the kinetochore
      microtubule association. These results indicate that Scc1 is essential for the
      association of kinetochores with microtubules.

PMID- 12200440
TI  - Biosynthesis of riboflavin in archaea studies on the mechanism of 3,4-dihydroxy-2
      butanone-4-phosphate synthase of Methanococcus jannaschii.
AB  - The hypothetical protein predicted by the open reading frame MJ0055 of
      Methanococcus jannaschii was expressed in a recombinant Escherichia coli strain
      under the control of a synthetic gene optimized for translation in an eubacterial
      host. The recombinant protein catalyzes the formation of the riboflavin precursor
      3,4-dihydroxy-2-butanone 4-phosphate from ribulose 5-phosphate at a rate of 174
      nmol mg(-1) min(-1) at 37 degrees C. The homodimeric 51.6-kDa protein requires
      divalent metal ions, preferentially magnesium, for activity. The reaction
      involves an intramolecular skeletal rearrangement as shown by (13)C NMR
      spectroscopy using [U-(13)C(5)]ribulose 5-phosphate as substrate. A cluster of
      charged amino acid residues comprising arginine 25, glutamates 26 and 28, and
      aspartates 21 and 30 is essential for catalytic activity. Histidine 164 and
      glutamate 185 were also shown to be essential for catalytic activity.

PMID- 12200441
TI  - A back-up glycosylase in Nth1 knock-out mice is a functional Nei (endonuclease
      VIII) homologue.
AB  - Thymine glycol, a potentially lethal DNA lesion produced by reactive oxygen
      species, can be removed by DNA glycosylase, Escherichia coli Nth (endonuclease
      III), or its mammalian homologue NTH1. We have found previously that mice deleted
      in the Nth homologue still retain at least two residual glycosylase activities
      for thymine glycol. We report herein that in cell extracts from the mNth1 knock
      out mouse there is a third thymine glycol glycosylase activity that is encoded by
      one of three mammalian proteins with sequence similarity to E. coli Fpg (MutM)
      and Nei (endonuclease VIII). Tissue expression of this mouse Nei-like (designated
      as Neil1) gene is ubiquitous but much lower than that of mNth1 except in heart,
      spleen, and skeletal muscle. Recombinant NEIL1 can remove thymine glycol and 5
      hydroxyuracil in double- and single-stranded DNA much more efficiently than 8
      oxoguanine and can nick the strand by an associated (beta-delta)
      apurinic/apyrimidinic lyase activity. In addition, the mouse NEIL1 has a unique
      DNA glycosylase/lyase activity toward mismatched uracil and thymine, especially
      in U:C and T:C mismatches. These results suggest that NEIL1 is a back-up
      glycosylase for NTH1 with unique substrate specificity and tissue-specific
      expression.

PMID- 12200442
TI  - Alternative splicing of the human diacylglycerol kinase delta gene generates two
      isoforms differing in their expression patterns and in regulatory functions.
AB  - Diacylglycerol kinase (DGK) plays an important role in signal transduction
      through modulating the balance between two signaling lipids, diacylglycerol and
      phosphatidic acid. DGKdelta (type II isozyme) contains a pleckstrin homology
      domain at the N terminus and a sterile alpha motif domain at the C terminus. We
      identified another DGKdelta isoform (DGKdelta2, 135 kDa) that shared the same
      sequence with DGKdelta previously cloned (DGKdelta1, 130 kDa) except for the 52
      residues N-terminally extended. Analysis of panels of human normal and tumor
      tissue cDNAs revealed that DGKdelta2 was ubiquitously expressed in all normal and
      tumor tissues examined, whereas the transcript of DGKdelta1 was detected only in
      ovary and spleen, and in a limited set of tumor-derived cells. The expression of
      DGKdelta2 was induced by treating cells with epidermal growth factor and tumor
      promoting phorbol ester. In contrast, the levels of mRNA and protein of DGKdelta1
      were suppressed by phorbol ester treatment. It thus becomes clear that the two
      DGKdelta isoforms are expressed under distinct regulatory mechanisms. DGKdelta1
      was translocated through its pleckstrin homology domain from the cytoplasm to the
      plasma membrane in response to phorbol ester stimulation, whereas DGKdelta2
      remained in the cytoplasm even after stimulation. Further experiments showed that
      the delta2-specific N-terminal sequence blocks the phorbol ester-dependent
      translocation of this isoform. Co-immunoprecipitation analysis of differently
      tagged DGKdelta1 and DGKdelta2 proteins showed that they were able to form homo-
      as well as hetero-oligomers. Taken together, alternative splicing of the human
      DGKdelta gene generates at least two isoforms, differing in their expressions and
      regulatory functions.

PMID- 12200443
TI  - Genetic analysis of adipogenesis through peroxisome proliferator-activated
      receptor gamma isoforms.
AB  - Peroxisome proliferator-activated receptor (PPAR) gamma is a nuclear receptor
      that is a key regulator of adipogenesis and is present in two isoforms generated
      by alternative splicing, PPARgamma1 and PPARgamma2. Studies of the ability of
      each isoform to stimulate fat differentiation have yielded ambiguous results, in
      part because PPARgamma stimulates its own expression. We have thus undertaken a
      formal genetic analysis using PPARgamma-null fibroblast cell lines to assess the
      specific role of each individual isoform in adipogenesis. We show here that both
      PPARgamma1 and PPARgamma2 have the intrinsic ability to stimulate robust
      adipogenesis. Adipose cells stimulated by either PPARgamma1 or PPARgamma2 express
      a similar gene profile and show similar responses to insulin. However, in
      response to low ligand concentrations, PPARgamma2 shows a quantitatively greater
      ability to induce adipogenesis. Analyses involving coactivator binding and
      transcriptional assays indicate that PPARgamma2 has an enhanced ability to bind
      components of the DRIP/TRAP complex, coactivators required for fat
      differentiation.

PMID- 12200444
TI  - A complex of the Srb8, -9, -10, and -11 transcriptional regulatory proteins from
      yeast.
AB  - The Srb8, -9, -10, and -11 proteins of yeast have been isolated as a discrete,
      stoichiometric complex. The isolated complex phosphorylates the C-terminal domain
      (CTD) of the largest subunit of RNA polymerase II at serines 2 and 5. In addition
      to the previously reported human homologs of Srb10 and 11, we have identified
      TRAP230/ARC240 and TRAP240/ARC250 as the human homologs of Srb8 and Srb9, showing
      the entire Srb8/9/10/11 complex is conserved from yeast to humans.

PMID- 12200445
TI  - AP endonuclease 1 coordinates flap endonuclease 1 and DNA ligase I activity in
      long patch base excision repair.
AB  - Base loss is common in cellular DNA, resulting from spontaneous degradation and
      enzymatic removal of damaged bases. Apurinic/apyrimidinic (AP) endonucleases
      recognize and cleave abasic (AP) sites during base excision repair (BER). APE1
      (REF1, HAP1) is the predominant AP endonuclease in mammalian cells. Here we
      analyzed the influences of APE1 on the human BER pathway. Specifically, APE1
      enhanced the enzymatic activity of both flap endonuclease1 (FEN1) and DNA ligase
      I. FEN1 was stimulated on all tested substrates, regardless of flap length.
      Interestingly, we have found that APE1 can also inhibit the activities of both
      enzymes on substrates with a tetrahydrofuran (THF) residue on the 5'-downstream
      primer of a nick, simulating a reduced abasic site. However once the THF residue
      was displaced at least a single nucleotide, stimulation of FEN1 activity by APE1
      resumes. Stimulation of DNA ligase I required the traditional nicked substrate.
      Furthermore, APE1 was able to enhance overall product formation in reconstitution
      of BER steps involving FEN1 cleavage followed by ligation. Overall, APE1 both
      stimulated downstream components of BER and prevented a futile cleavage and
      ligation cycle, indicating a far-reaching role in BER.

PMID- 12200446
TI  - Acute activation of de novo sphingolipid biosynthesis upon heat shock causes an
      accumulation of ceramide and subsequent dephosphorylation of SR proteins.
AB  - Recent studies are beginning to implicate sphingolipids in the heat stress
      response. In the yeast Saccharomyces cerevisiae, heat stress has been shown to
      activate de novo biosynthesis of sphingolipids, whereas in mammalian cells the
      sphingolipid ceramide has been implicated in the heat shock responses. In the
      current study, we found an increase in the ceramide mass of Molt-4 cells in
      response to heat shock, corroborating findings in HL-60 cells. Increased ceramide
      was determined to be from de novo biosynthesis by two major lines of evidence.
      First, the accumulation of ceramide was dependent upon the activities of both
      ceramide synthase and serine palmitoyltransferase. Second, pulse labeling studies
      demonstrated increased production of ceramide through the de novo biosynthetic
      pathway. Significantly, the de novo sphingolipid biosynthetic pathway was acutely
      induced upon heat shock, which resulted in a 2-fold increased flux in newly made
      ceramides within 1-2 min of exposure to 42.5 degrees C. Functionally, heat shock
      induced the dephosphorylation of the SR proteins, and this effect was
      demonstrated to be dependent upon the accumulation of de novo-produced ceramides.
      Thus, these studies disclose an evolutionary conserved activation of the de novo
      pathway in response to heat shock. Moreover, SR dephosphorylation is emerging as
      a specific downstream target of accumulation of newly made ceramides in mammalian
      cells.

PMID- 12200447
TI  - Binding of C/EBP and RBP (CBF1) to overlapping sites regulates interleukin-6 gene
      expression.
AB  - The ILRE (interleukin response element) contained within the promoter of the
      interleukin-6 (IL-6) gene is defined as the site recognized by the p65 NF-kappaB
      transcriptional activator and is crucial for activation of the IL-6 gene. The
      region of the promoter containing the ILRE is complex containing a CCAAT enhancer
      binding protein (C/EBP) site immediately upstream of the ILRE, which is required
      for optimal activation of the IL-6 gene. Additionally, the ILRE overlaps a site
      that is recognized by the mammalian transcriptional repressor RBP (CBF-1), and
      RBP binding within the ILRE region represses activated IL-6 expression. In this
      study, the complexity of this region is further revealed by the identification of
      a second nested C/EBP site, which overlaps that of RBP and therefore also the
      ILRE. Optimal activation requires both the upstream and newly identified C/EBP
      sites in conjunction with the p65 NF-kappaB binding site. We previously reported
      that RBP represses IL-6 activation but does not target p65. We extend these
      analyses here to show that RBP binding does not occlude p65 from binding but
      instead directly overlaps the newly identified downstream C/EBP site, thereby
      impeding p65-C/EBP-mediated co-activation. This result suggests a role for RBP in
      the repression of other genes containing a C/EBP site that exhibits sequence
      overlap with the RBP site.

PMID- 12200449
TI  - GAGA factor down-regulates its own promoter.
AB  - GAGA factor is involved in many nuclear transactions, notably in transcription as
      an activator in Drosophila. The genomic region corresponding to the Trl promoter
      has been obtained, and a minimal version of a fully active Trl promoter has been
      defined using transient transfection assays in S2 cells. DNase I footprinting
      analysis has shown that this region contains multiple GAGA binding sites,
      suggesting a potential regulatory role of GAGA on its own promoter. The study
      shows that GAGA down-regulates Trl expression. The repression does not depend on
      the GAGA isoform, but binding to DNA is absolutely required. A fragment of the
      Trl promoter can mediate repression to a heterologous promoter only upon GAGA
      overexpression in transiently transfected S2 cells. Chromatin immunoprecipitation
      analysis of S2 cells confirmed that GAGA factors are bound to the Trl promoter
      over a region of 1.4 kbp. Using a double-stranded RNA interference approach, we
      show that endogenous GAGA factors limit Trl expression in S2 cells. Our results
      open the possibility of observing similar GAGA repressive effects on other
      promoters.

PMID- 12200448
TI  - Transcriptional activation of interleukin-8 by beta-catenin-Tcf4.
AB  - Nuclear translocation of beta-catenin and its association with Tcf/Lef factors
      are key steps in transduction of the Wnt signal, which is aberrantly activated in
      a variety of human cancers. In a search for new beta-catenin-Tcf target genes, we
      analyzed beta-catenin-induced alterations of gene expression in primary human
      hepatocytes, after transduction of either dominant stable beta-catenin or its
      truncated, transactivation-deficient counterpart by means of a lentiviral vector.
      cDNA microarray analysis revealed a limited set of up-regulated genes, including
      known Wnt targets such as matrilysin and keratin-1. In this screen, we identified
      the CXC chemokine interleukin 8 (IL-8) as a direct target of beta-catenin-Tcf4.
      IL-8 is constitutively expressed in various cancers, and it has been implicated
      in tumor progression through its mitogenic, motogenic, and angiogenic activities.
      The IL-8 promoter contains a unique consensus Tcf/Lef site that is critical for
      IL-8 activation by beta-catenin. We show here that the p300 coactivator was
      required for efficient transactivation of beta-catenin on this promoter. Ectopic
      expression of beta-catenin in hepatoma cells promoted IL-8 secretion, which
      stimulated endothelial cell migration. These data define IL-8 as a Wnt target and
      suggest that IL-8 induction by beta-catenin might be implicated in developmental
      and tumorigenic processes.

PMID- 12200450
TI  - Biochemical characterization of the Pseudomonas putida 3-hydroxyacyl ACP:CoA
      transacylase, which diverts intermediates of fatty acid de novo biosynthesis.
AB  - The 3-hydroxyacyl ACP:CoA transacylase (PhaG) was recently identified in various
      Pseudomonas species and catalyzes the diversion of ACP thioester intermediates of
      fatty acid de novo biosynthesis toward the respective CoA thioesters, which serve
      as precursors for polyester and rhamnolipid biosynthesis. PhaG from Pseudomonas
      putida was overproduced in Escherichia coli as a C-terminal hexahistidine-tagged
      (His(6)) fusion protein in high yield. The His(6)-PhaG was purified to
      homogeneity by refolding of PhaG obtained from inclusion bodies, and a new enzyme
      assay was established. Kinetic analysis of the 3-hydroxyacyl transfer to ACP,
      catalyzed by His(6)-PhaG, gave K(0.5) values of 28 microm (ACP) and 65 microm (3
      hydroxyacyl-CoA) considering V(max) values of 11.7 milliunits/mg and 12.4
      milliunits/mg, respectively. A Hill coefficient of 1.38 (ACP) and 1.32 (3
      hydroxyacyl-CoA) indicated a positive substrate cooperativity. Subcellular
      localization studies showed that PhaG is not attached to polyester granules and
      resides in the cytosol. Gel filtration chromatography analysis in combination
      with light scattering analysis indicated substrate-induced dimerization of the
      transacylase. A threading model of PhaG was developed based on the homology to an
      epoxide hydrolase (1cqz). In addition, the alignment with the alpha/beta
      hydrolase fold region indicated that PhaG belongs to alpha/beta-hydrolase
      superfamily. Accordingly, CD analysis suggested a secondary structure composition
      of 29% alpha-helix, 22% beta-sheet, 18% beta-turn, and 31% random coil. Site
      specific mutagenesis of seven highly conserved amino acid residues (Asp-60, Ser
      102, His-177, Asp-182, His-192, Asp-223, His-251) was used to validate the
      protein model and to investigate organization of the transacylase active site.
      Only the D182(A/E) mutation was permissive with about 30% specific activity of
      the wild type enzyme. Furthermore, this mutation caused a change in substrate
      specificity, indicating a functional role in substrate binding. The serine
      specific agent phenylmethylsulfonyl fluoride (PMSF) or the histidine-specific
      agent diethylpyrocarbonate (DEPC) caused inhibition of 3-hydroxyacyl transfer to
      holo-ACP, and the S102(A/T) or H251(A/R) PhaG mutant was incapable of catalyzing
      3-hydroxyacyl transfer, suggesting that these residues are part of a catalytic
      triad.

PMID- 12200451
TI  - The CY domain of the Fcgamma RIa alpha-chain (CD64) alters gamma-chain tyrosine
      based signaling and phagocytosis.
AB  - Although the cytoplasmic domain of the human FcgammaRIa alpha-chain lacks
      tyrosine-based phosphorylation motifs, it modulates receptor cycling and receptor
      specific cytokine production. The cytoplasmic domain of FcgammaRIa is
      constitutively phosphorylated, and the inhibition of dephosphorylation with
      okadaic acid, an inhibitor of type 1 and type 2A protein serine/threonine
      phosphatase, inhibits both receptor-induced activation of the early tyrosine
      phosphorylation cascade and receptor-specific phagocytosis. To explore the basis
      for these effects of the cytoplasmic domain of FcgammaRIa, we developed a series
      of human FcgammaRIa molecular variants, expressed in the murine macrophage cell
      line P388D1, and demonstrate that serine phosphorylation of the cytoplasmic
      domain is an important regulatory mechanism. Truncation of the cytoplasmic domain
      and mutation of the cytoplasmic domain serine residues to alanine abolish the
      okadaic acid inhibition of phagocytic function. In contrast, the serine mutants
      did not recapitulate the selective effects of cytoplasmic domain truncation on
      cytokine production. These results demonstrate for the first time a direct
      functional role for serine phosphorylation in the alpha-chain of FcgammaRIa and
      suggest that the cytoplasmic domain of FcgammaRI regulates the different
      functional capacities of the FcgammaRIa-receptor complex.

PMID- 12200452
TI  - Exploring the effects of active site constraints on HIV-1 reverse transcriptase
      DNA polymerase fidelity.
AB  - To examine the concept of polymerase active site tightness as a criteria for DNA
      polymerase fidelity, we performed pre-steady-state single nucleotide
      incorporation kinetic analyses with sugar modified thymidine 5'-triphosphate
      (TTP) analogues and human immunodeficiency virus (HIV-1) reverse transcriptase
      (RT). The employed TTP analogues (T(R)TP) are modified at the 4'-position of the
      sugar moiety with alkyl groups, gradually expanding their steric demand.
      Introduction of a methyl group reduces the maximum rate of nucleotide
      incorporation by about 200-fold for RT(WT) and about 400-fold for RT(M184V).
      Interestingly, the affinity of RT for the modified nucleotide is only marginally
      affected. Increasing the size to an ethyl group leads to further reduction of the
      rate of incorporation and first effects on binding affinities are observed.
      Finally, substitution for an isopropyl group results not only in a further
      reduction of incorporation rates but also in a dramatic loss of binding affinity
      for the nucleotide analogue. By increasing the steric demand the effects on
      RT(M184V) in comparison with RT(WT) become progressively more pronounced.
      Misincorporation of either TTP or T(Me)TP opposite a template G causes additional
      decline in incorporation rates accompanied by a drastic decrease in binding
      affinities. This results in relative incorporation efficiencies
      [(k(pol)/K(d))(incorrect)/(k(pol)/K(d))(TTPcorrect)] of 4.1 x 10(-5) for TTP and
      3.4 x 10(-6) for T(Me)TP in case of RT(WT) and 1.4 x 10(-5) for TTP and 2.9 x 10(
      8) for T(Me)TP in case of RT(M184V).

PMID- 12200453
TI  - Multiple, conserved iron-responsive elements in the 3'-untranslated region of
      transferrin receptor mRNA enhance binding of iron regulatory protein 2.
AB  - Synthesis of proteins for iron homeostasis is regulated by specific,
      combinatorial mRNA/protein interactions between RNA stem-loop structures (iron
      responsive elements, IREs) and iron-regulatory proteins (IRP1 and IRP2),
      controlling either mRNA translation or stability. The transferrin receptor 3'
      untranslated region (TfR-3'-UTR) mRNA is unique in having five IREs, linked by AU
      rich elements. A C-bulge in the stem of each TfR-IRE folds into an IRE that has
      low IRP2 binding, whereas a loop/bulge in the stem of the ferritin-IRE allows
      equivalent IRP1 and IRP2 binding. Effects of multiple IRE interactions with IRP1
      and IRP2 were compared between the native TfR-3'-UTR sequence (5xIRE) and RNA
      with only 3 or 2 IREs. We show 1) equivalent IRP1 and IRP2 binding to multiple
      TfR-IRE RNAs; 2) increased IRP-dependent nuclease resistance of 5xIRE compared
      with lower IRE copy-number RNAs; 3) distorted TfR-IRE helix structure within the
      context of 5xIRE, detected by Cu-(phen)(2) binding/cleavage, that coincides with
      ferritin-IRE conformation and enhanced IRP2 binding; and 4) variable IRP1 and
      IRP2 expression in human cells and during development (IRP2-mRNA predominated).
      Changes in TfR-IRE structure conferred by the full length TfR-3'-UTR mRNA explain
      in part evolutionary conservation of multiple IRE-RNA, which allows TfR mRNA
      stabilization and receptor synthesis when IRP activity varies, and ensures iron
      uptake for cell growth.

PMID- 12200454
TI  - Upstream elements present in the 3'-untranslated region of collagen genes
      influence the processing efficiency of overlapping polyadenylation signals.
AB  - 3'-Untranslated regions (UTRs) of genes often contain key regulatory elements
      involved in gene expression control. A high degree of evolutionary conservation
      in regions of the 3'-UTR suggests important, conserved elements. In particular,
      we are interested in those elements involved in regulation of 3' end formation.
      In addition to canonical sequence elements, auxiliary sequences likely play an
      important role in determining the polyadenylation efficiency of mammalian pre
      mRNAs. We identified highly conserved sequence elements upstream of the AAUAAA in
      three human collagen genes, COL1A1, COL1A2, and COL2A1, and demonstrate that
      these upstream sequence elements (USEs) influence polyadenylation efficiency.
      Mutation of the USEs decreases polyadenylation efficiency both in vitro and in
      vivo, and inclusion of competitor oligoribonucleotides representing the USEs
      specifically inhibit polyadenylation. We have also shown that insertion of a USE
      into a weak polyadenylation signal can enhance 3' end formation. Close inspection
      of the COL1A2 3'-UTR reveals an unusual feature of two closely spaced, competing
      polyadenylation signals. Taken together, these data demonstrate that USEs are
      important auxiliary polyadenylation elements in mammalian genes.

PMID- 12200455
TI  - Relaxin enhances in-vitro invasiveness of breast cancer cell lines by up
      regulation of matrix metalloproteases.
AB  - Until recently, relaxin (RLX) has been known predominantly for its effects on the
      reproductive system, where it induces remodelling of the extracellular matrix and
      up-regulation of matrix metalloproteases (MMPs). In solid cancers, tissue
      remodelling and MMP activation are essential for invasion and metastasis. We
      therefore investigated the effect of RLX on invasiveness and MMP expression of
      human breast cancer cell lines. Upon incubation with porcine RLX, the
      invasiveness of SK-BR3 cells was significantly increased. Similar effects could
      be achieved in MCF-7 cells, especially when RLX was combined with epidermal
      growth factor. Enhanced invasiveness was accompanied by up-regulation of MMP
      production and could be almost completely blocked by the MMP inhibitor FN 439.
      Zymography revealed increased secretion of MMP-2, -7 and -9, associated with up
      regulated mRNA concentrations of MMP-2, -9, -13 and -14. mRNA expression levels
      of MMP-1, -3, -7, -8, -10, -11, -12 and of tissue inhibitors of metalloproteases
      1, -2, -3 and -4 were either very low or not detectably influenced by RLX. Taken
      together, RLX enhances in-vitro invasiveness of breast cancer cell lines by
      induction of MMP expression. It remains to be clarified whether RLX might play a
      similar role in vivo and promote tumour progression.

PMID- 12200456
TI  - Partial rescue of the Dazl knockout mouse by the human DAZL gene.
AB  - Y-chromosomal DAZ (deleted in azoospermia) and autosomal DAZ-like (DAZL) comprise
      a gene family involved in gametogenesis. Y-chromosomal and autosomal genes only
      co-exist in humans and old world monkeys, indicating that DAZ genes are a recent
      acquisition of the Y chromosome. In most mammals, the ancestral Dazl alone is
      sufficient to complete gametogenesis. It is not yet understood why humans and old
      world monkeys have a second set of genes that are apparently necessary for
      spermatogenesis, since deletions removing the Y-chromosomal DAZ are often
      associated with azoo- or oligospermia. We used transgenic mice carrying either
      human DAZL or human DAZ on a mouse Dazl null background to investigate the
      functions of the human homologues. Both transgenes enabled prophase spermatocytes
      to be produced, mainly of the leptonema/zygonema stage, but failed to promote
      differentiation into mid- to late pachytenes. The presence of human DAZL resulted
      in a larger amount of early germ cells compared with that observed in DAZ. The
      degree of rescue was independent of copy number, integration site or presence of
      the DAZ repeat region for the DAZ transgenes. These findings confirm that DAZL
      and DAZ can only substitute for early functions of the murine homologue resulting
      in the establishment of the germ cell population and partial progression into
      meiosis.

PMID- 12200457
TI  - Semenogelin I and II, the predominant human seminal plasma proteins, are also
      expressed in non-genital tissues.
AB  - Semenogelin I (SgI) and semenogelin II (SgII) are the dominating protein
      components of the coagulum formed by freshly ejaculated human semen. The primary
      source of these proteins is the seminal vesicles and, apart from a small
      production of SgII in epididymis, they have not been detected in other tissues.
      In this report, we have re-examined the distribution of SgI and SgII transcripts
      and protein by RT-PCR and immunohistochemistry. Both SgI and SgII transcripts
      were demonstrated in several tissues, with the strongest signals coming from
      seminal vesicles, vas deferens, prostate, epididymis and trachea. Transcripts in
      the gastro-intestinal tract and skeletal muscle almost exclusively encoded SgI,
      whereas in kidney and testis, SgII transcripts were predominant. By
      immunohistochemistry, the basal cell layer of the secretory epithelium in
      prostate, trachea and bronchi was stained by antibodies recognizing both SgI and
      SgII. This is in contrast to the seminal vesicle and vas deferens, where the
      luminal cells were stained. The staining of skeletal muscle cells and a few
      scattered cells in the central nervous system suggests that semenogelin
      expression is not restricted to epithelial cells.

PMID- 12200458
TI  - Different signal transduction pathways are involved during human sperm
      capacitation induced by biological and pharmacological agents.
AB  - Human sperm capacitation involves complex signal transduction mechanisms during
      which double phosphorylation of the threonine-glutamine-tyrosine motif (P-Thr-Glu
      Tyr-P) occurs in some sperm proteins. The objective of this study was to
      investigate the regulation of this process. Fetal cord serum ultrafiltrate
      (FCSu), follicular fluid ultrafiltrate (FFu), progesterone and a combination of
      N(6),2'-O-dibutyryl cAMP (dbcAMP; cell permeant analogue of cAMP) and 3-isobutyl
      1-methylxanthine (IBMX; phosphodiesterase inhibitor) were used as inducers of
      capacitation alone or in combination with inhibitors of protein kinase A (H89),
      protein kinase C (chelerythrine), protein tyrosine kinase (tyrphostin A47, PP2)
      and of dual specificity kinase (MEK-like kinases; PD98059). The level of P-Thr
      Glu-Tyr-P in sperm proteins of 80 and 105 kDa during capacitation induced by
      FCSu, FFu and progesterone was regulated by a similar signal transduction pathway
      and involved receptor type protein tyrosine kinase and dual specificity kinase
      (MEK or MEK-like) but not protein kinase A or C. However, the level of P-Thr-Glu
      Tyr-P in these sperm proteins during capacitation induced by dbcAMP+IBMX was
      mainly mediated through protein kinase A and C and receptor type protein tyrosine
      kinase, but not by dual specificity kinase. In conclusion, human sperm
      capacitation induced by some biological and pharmacological agents is regulated
      through very different signal transduction pathways.

PMID- 12200459
TI  - Human tMDC III: a sperm protein with a potential role in oocyte recognition.
AB  - A number of MDC (metalloproteinase-like, disintegrin-like, cysteine-rich)
      proteins are exclusively or abundantly expressed on mammalian sperm from a range
      of species, with data from rodents supporting a role for some of these in oolemma
      binding. However, in the human, transcripts for three of the most likely
      candidates have been shown to contain deletions and in-frame termination codons,
      rendering them non-functional. In this paper we have addressed the expression, in
      humans, of an additional MDC protein, tMDC III (also known as ADAM 18),
      previously shown to be exclusively expressed on sperm from rodents and macaques.
      Using a PCR-based approach, we have determined the complete nucleotide sequence
      of human tMDC III cDNA which, unlike the three non-functional genes, contains an
      uninterrupted open reading frame encoding a full-length MDC protein. Furthermore,
      polyclonal antisera raised against human recombinant tMDC III demonstrated the
      presence of mature protein on human sperm. In common with orthologues from other
      species, human tMDC III contains a putative integrin-binding glu-cys-asp (ECD)
      motif, the relevance of which is discussed in the context of a possible role in
      oolemma binding.

PMID- 12200460
TI  - A 60-66 kDa protein with gonadotrophin surge attenuating factor bioactivity is
      produced by human ovarian granulosa cells.
AB  - We aimed to confirm the ovarian site of gonadotrophin surge-attenuating factor
      (GnSAF) production and produce granulosa/luteal cell-conditioned medium (G/LCM)
      containing GnSAF for purification studies. Blue dye affinity chromatography
      followed by pseudochromatofocusing of G/LCM yielded bioactive fractions at pH
      5.74 and 5.77. The former had a major 60-66 kDa band with an internal amino acid
      sequence of EPQVYVHAP following tryptic digestion. A rat polyclonal antiserum
      (rPAb) raised against this band completely blocked in-vitro GnSAF bioactivity in
      human follicular fluid, serum and G/LCM. GnSAF bioactivity was localized to a 64
      kDa band of serum-free G/LCM and following 2D gel electrophoresis, one of the
      spots recognized by Western blotting with the GnSAF rPAb had an N-terminal amino
      acid sequence of NH-XVPQGNAXXN. Neither amino acid sequence had significant
      homology with proteins in the human genome database. When ovarian tissues from
      spontaneously cycling women were cultured under serum-free conditions, neither
      theca- nor stroma-conditioned media contained GnSAF bioactivity. However,
      granulosa cell-conditioned medium significantly reduced GnRH-induced LH
      secretion, an effect that was reversed by incubation with the GnSAF rPAb. In
      conclusion, we have confirmed that human granulosa cells produce GnSAF within the
      ovary and have two candidate amino acid sequences for GnSAF. We have also
      demonstrated that serum-free granulosa cell culture constitutes the method of
      choice for the characterization of GnSAF since recovery of bioactivity is
      superior in the presence of fewer serum proteins.

PMID- 12200461
TI  - Dynamic expression of mRNAs and proteins for matrix metalloproteinases and their
      tissue inhibitors in the primate corpus luteum during the menstrual cycle.
AB  - Matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs) may be
      involved in tissue remodelling in the primate corpus luteum (CL). MMP/TIMP mRNA
      and protein patterns were examined using real-time PCR and immunohistochemistry
      in the early, mid-, mid-late, late and very late CL of rhesus monkeys. MMP-1
      (interstitial collagenase) mRNA expression peaked (by >7-fold) in the early CL.
      MMP-9 (gelatinase B) mRNA expression was low in the early CL, but increased 41
      fold by the very late stage. MMP-2 (gelatinase A) mRNA expression tended to
      increase in late CL. TIMP-1 mRNA was highly expressed in the CL, until declining
      21-fold by the very late stage. TIMP-2 mRNA expression was high through the mid
      luteal phase. MMP-1 protein was detected by immunocytochemistry in early
      steroidogenic cells. MMP-2 protein was prominent in late, but not early CL
      microvasculature. MMP-9 protein was noted in early CL and labelling increased in
      later stage steroidogenic cells. TIMP-1 and -2 proteins were detected in
      steroidogenic cells at all stages. Thus, MMPs and TIMPs are dynamically expressed
      in a cell-specific manner in the primate CL. Early expression of MMP-1 is
      suggestive of a role in tissue remodelling associated with luteinization, whereas
      MMP-2 and -9 may contribute to later stage luteolysis. TIMP expression may
      control MMP activity, until declining at luteolysis.

PMID- 12200462
TI  - Expression of interleukin (IL)-11 receptor by the human endometrium in vivo and
      effects of IL-11, IL-6 and LIF on the production of MMP and cytokines by human
      endometrial cells in vitro.
AB  - Interleukin (IL)-6, leukaemia inhibitory factor (LIF) and IL-11 belong to the
      same family of cytokines whose receptors utilize gp130 as the signalling
      molecule. We have investigated the expression of the IL-11 receptor, IL-11Ralpha,
      protein in the human endometrium in vivo and the effects of IL-6, LIF and IL-11
      on the production of metalloproteinases (MMPs) and cytokines by cultured
      endometrial epithelial and stromal cells. Immunostaining showed that IL-11Ralpha
      was expressed in both epithelial and stromal cells, with epithelial staining
      being more intense than stromal staining and little variation in staining in
      either compartment throughout the cycle. Incubation of both stromal and
      epithelial cells with IL-6, LIF and IL-11 had no effect on MMP-2, -7, -9,
      transforming growth factor (TGF)beta or IL-1beta production or cell growth. IL-6
      and LIF also had no effect on tumour necrosis factor (TNF)alpha production, but
      IL-11 caused a dose-dependent decrease in TNFalpha production by epithelial
      cells. IL-6 receptor, LIF receptor and gp130 were all expressed by cultured
      stromal and epithelial cells, showing that the lack of effect is not due to lack
      of expression of the receptor components. The results show that although IL-6,
      LIF and IL-11 signal through the same molecule, they may have different effects
      in endometrial cells, suggesting the activation of different signalling pathways,
      which may ultimately be important in the control of endometrial function.

PMID- 12200463
TI  - Dioxin stimulates RANTES expression in an in-vitro model of endometriosis.
AB  - The industrial contaminant 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) is
      associated with inflammatory disorders in women and other mammals. The current
      studies were performed to investigate the effect of TCDD on RANTES expression in
      an in-vitro model of endometriosis. The biochemical effects of dioxins are
      mediated by binding to aryl hydrocarbon receptors (AhR). This study showed that
      both normal and endometriotic endometrial stromal cells express AhR protein,
      which was observed to be down-regulated by 40-60% after exposure to TCDD.
      Treatment with TCDD for 24 h increased the luciferase activity of the RANTES
      promoter by 2.5 +/- 1.0-fold in stromal cells derived from normal endometrium and
      endometriotic implants. When AhR were over-expressed in these cells, luciferase
      activity increased 6.1 +/- 1.4-fold, and RANTES protein secretion increased from
      undetectable to 31 +/- 10 pg/100,000 cells. TCDD failed to activate a RANTES
      construct with a mutated dioxin response element. Other AhR ligands had similar
      effects to TCDD on RANTES transcription and secretion. Control transfections
      using tumour necrosis factor (TNF)-alpha and nuclear factor (NF)-kappaB response
      element reporters indicated that these pathways are not activated by TCDD in
      endometrial stromal cells. This study has demonstrated that functional AhR are
      present in endometrial and endometriotic stromal cells and that TCDD up-regulates
      the expression of RANTES, providing a possible mechanistic link between dioxin
      exposure and chemokine expression in endometriosis.

PMID- 12200464
TI  - Microarray analysis of VEGF-responsive genes in myometrial endothelial cells.
AB  - There is evidence that the vasculature of different organs display different
      functional characteristics in response to cytokines and growth factors. The aim
      of this study was to use cDNA gene expression microarray to analyse changes in
      gene expression following stimulation of myometrial microvascular endothelial
      cells (MMECs) with vascular endothelial growth factor (VEGF). Primary isolates of
      MMECs were obtained from fresh hysterectomy specimens and purified with magnetic
      beads. Cells were stimulated with 15 ng/ml VEGF for 3, 6 and 12 h, and two
      unstimulated experiments served as controls. A total of six arrays was performed
      over these time-points. A total of 110 genes were identified as up-regulated by
      VEGF, 19% of which (21 genes) have previously been reported as up-regulated by
      VEGF or by angiogenesis. Among the novel genes to be up-regulated by VEGF were
      brain-derived growth factor, oxytocin receptor and estrogen sulphotransferase.
      The significance of the genes identified in the physiological and pathological
      functioning of the myometrial vasculature is discussed.

PMID- 12200465
TI  - Cell-free fetal DNA in the maternal circulation does not stem from the
      transplacental passage of fetal erythroblasts.
AB  - Fetal cells, specifically fetal erythroblasts, as well as cell-free fetal DNA are
      present in the maternal circulation. Both are currently being investigated as a
      means for the non-invasive risk-free analysis of fetal genetic traits. The origin
      of this cell-free fetal DNA in the maternal circulation is currently unclear.
      Since numerous fetal erythroblasts have been demonstrated to exhibit an apoptotic
      phenotype in the form of fragmented nuclear DNA, it has been proposed that such
      trafficking fetal cells may be a possible source. This hypothesis is supported by
      reports of elevated numbers of fetal erythroblast and cell-free fetal DNA
      concentrations in pregnancies affected by pre-eclampsia or polyhydramnios. To
      address this question, we have examined fetal erythroblast numbers and cell-free
      DNA concentrations in the same maternal blood samples. Our study, performed on
      both normal and pathologically-affected pregnancies, indicates that no
      correlation exists between these two fetal cellular and molecular species. This
      is most evident in pregnancies affected by onset of preterm labour, where
      significant elevations in cell-free fetal DNA concentrations were detected
      without any concomitant elevation in fetal erythroblast numbers. Our data
      therefore suggest that an alternative cell type is the source of cell-free fetal
      DNA. Furthermore, it appears that the release of cell-free fetal DNA from this
      cell type is affected by pathological placental conditions which are not
      associated with an increase in fetal cell trafficking.

PMID- 12200466
TI  - Changes in gene expression during the early to mid-luteal (receptive phase)
      transition in human endometrium detected by high-density microarray screening.
AB  - High density cDNA microarray screening was used to determine changes in gene
      expression occurring during the transition between the early luteal
      (prereceptive) and mid-luteal (receptive) phases in human endometrium. Of
      approximately 12,000 genes profiled, 693 (5.8%) displayed >2-fold differences in
      relative levels of expression between these stages. Of these, 370 genes (3.1%)
      displayed decreases ranging from 2- to >100-fold while 323 genes (2.7%) displayed
      increases ranging from 2- to >45-fold. Many genes correspond to mRNAs encoding
      proteins previously shown to change in a similar manner between the proliferative
      and mid-luteal phases, serving as one validation of the microarray screening
      results. In addition, novel genes were identified. Genes encoding cell surface
      receptors, adhesion and extracellular matrix proteins and growth factors
      accounted for 20% of the changes. Several genes were studied further by Northern
      blot analyses. These results confirmed that claudin-4/Clostridium perfringens
      enterotoxin (CPE) receptor and osteopontin (OPN) mRNA increased approximately 4-
      and 12-fold respectively, while betaig-H3 (BIGH3) decreased >80% during the early
      to mid-luteal transition. Immunostaining also revealed strong specific staining
      for claudin-4/CPE, EP(1) and prostaglandin receptor in epithelia, and leukotriene
      B4 receptor in both epithelia and stroma, at the mid-luteal stage. Collectively,
      these studies identify multiple new candidate markers that may be used to predict
      the receptive phase in humans. Some of these gene products, e.g. OPN, may play
      direct roles in embryo-uterine interactions during the implantation process.

PMID- 12200467
TI  - Multiplex sequence variation detection throughout the CFTR gene appropriate for
      preimplantation genetic diagnosis in populations with heterogeneity of cystic
      fibrosis mutations.
AB  - Cystic fibrosis (CF) is one of the most important genetic diseases requiring
      prevention programmes. Preimplantation genetic diagnosis (PGD) represents an
      alternative to prenatal diagnosis, and is especially appropriate for couples with
      an unsuccessful reproductive history. For clinical application, protocols must be
      optimized to minimize PCR failure, allelic drop-out (ADO) and contamination,
      while simultaneously detecting a wide spectrum of CF genotypes. We have developed
      a flexible multiplex PCR protocol allowing analysis of sequence variations in any
      combination amongst seven CFTR gene exons (4, 10, 11, 13 in two parts, 14b, 17b
      and 21) by nested PCR and denaturing gradient gel electrophoresis analysis, along
      with analysis of a fluorescently labelled intragenic microsatellite (IVS8CA). The
      experiments were carried out on 390 single lymphocytes from three CF patients,
      one heterozygote and one non-CF individual. PCR efficiency of the exons ranged
      from 90 to 100%, and ADO from 0 to 3.8%. IVS8CA was co-amplified with a PCR
      efficiency of 92.4 and 10.8% ADO. The present method overcomes the need for
      separate assays for each CFTR gene mutation. Additionally, it facilitates
      analysis of any informative linked polymorphic sequence variation (within the
      seven exons) along with analysis of a microsatellite, which is useful (when
      informative) for minimizing misdiagnosis and/or indirect diagnosis. This method
      proved robust and flexible for diagnosing diverse CF genotype combinations in
      single cells.

PMID- 12200468
TI  - Hill-Robertson interference is a minor determinant of variations in codon bias
      across Drosophila melanogaster and Caenorhabditis elegans genomes.
AB  - According to population genetics models, genomic regions with lower crossing-over
      rates are expected to experience less effective selection because of Hill
      Robertson interference (HRi). The effect of genetic linkage is thought to be
      particularly important for a selection of weak intensity such as selection
      affecting codon usage. Consistent with this model, codon bias correlates
      positively with recombination rate in Drosophila melanogaster and Caenorhabditis
      elegans. However, in these species, the G+C content of both noncoding DNA and
      synonymous sites correlates positively with recombination, which suggests that
      mutation patterns and recombination are associated. To remove this effect of
      mutation patterns on codon bias, we used the synonymous sites of lowly expressed
      genes that are expected to be effectively neutral sites. We measured the
      differences between codon biases of highly expressed genes and their lowly
      expressed neighbors. In D. melanogaster we find that HRi weakly reduces selection
      on codon usage of genes located in regions of very low recombination; but these
      genes only comprise 4% of the total. In C. elegans we do not find any evidence
      for the effect of recombination on selection for codon bias. Computer simulations
      indicate that HRi poorly enhances codon bias if the local recombination rate is
      greater than the mutation rate. This prediction of the model is consistent with
      our data and with the current estimate of the mutation rate in D. melanogaster.
      The case of C. elegans, which is highly self-fertilizing, is discussed. Our
      results suggest that HRi is a minor determinant of variations in codon bias
      across the genome.

PMID- 12200469
TI  - Rates and patterns of molecular evolution in inbred and outbred Arabidopsis.
AB  - The evolution of self-fertilization is associated with a large reduction in the
      effective rate of recombination and a corresponding decline in effective
      population size. If many spontaneous mutations are slightly deleterious, this
      shift in the breeding system is expected to lead to a reduced efficacy of natural
      selection and genome-wide changes in the rates of molecular evolution. Here, we
      investigate the effects of the breeding system on molecular evolution in the
      highly self-fertilizing plant Arabidopsis thaliana by comparing its coding and
      noncoding genomic regions with those of its close outcrossing relative, the self
      incompatible A. lyrata. More distantly related species in the Brassicaceae are
      used as outgroups to polarize the substitutions along each lineage. In contrast
      to expectations, no significant difference in the rates of protein evolution is
      observed between selfing and outcrossing Arabidopsis species. Similarly, no
      consistent overall difference in codon bias is observed between the species,
      although for low-biased genes A. lyrata shows significantly higher major codon
      usage. There is also evidence of intron size evolution in A. thaliana, which has
      consistently smaller introns than its outcrossing congener, potentially
      reflecting directional selection on intron size. The results are discussed in the
      context of heterogeneity in selection coefficients across loci and the effects of
      life history and population structure on rates of molecular evolution. Using
      estimates of substitution rates in coding regions and approximate estimates of
      divergence and generation times, the genomic deleterious mutation rate (U) for
      amino acid substitutions in Arabidopsis is estimated to be approximately 0.2-0.6
      per generation.

PMID- 12200470
TI  - Evolution of the sulfide-binding function within the globin multigenic family of
      the deep-sea hydrothermal vent tubeworm Riftia pachyptila.
AB  - The giant extracellular hexagonal bilayer hemoglobin (HBL-Hb) of the deep-sea
      hydrothermal vent tube worm Riftia pachyptila is able to transport simultaneously
      O(2) and H(2)S in the blood from the gills to a specific organ: the trophosome
      that harbors sulfide-oxidizing endosymbionts. This vascular HBL-Hb is made of 144
      globins from which four globin types (A1, A2, B1, and B2) coevolve. The H(2)S is
      bound at a specific location (not on the heme site) onto two of these globin
      types. In order to understand how such a function emerged and evolved in
      vestimentiferans and other related annelids, six partial cDNAs corresponding to
      the six globins known to compose the multigenic family of R. pachyptila have been
      identified and sequenced. These partial sequences (ca. 120 amino acids, i.e., 80%
      of the entire protein) were used to reconstruct molecular phylogenies in order to
      trace duplication events that have led to the family organization of these
      globins and to locate the position of the free cysteine residues known to bind
      H(2)S. From these sequences, only two free cysteine residues have been found to
      occur, at positions Cys + 1 (i.e., 1 a.a. from the well-conserved distal
      histidine) and Cys + 11 (i.e., 11 a.a. from the same histidine) in globins B2 and
      A2, respectively. These two positions are well conserved in annelids,
      vestimentiferans, and pogonophorans, which live in sulfidic environments. The
      structural comparison of the hydrophobic environment that surrounds these
      cysteine residues (the sulfide-binding domain) using hydrophobic cluster analysis
      plots, together with the cysteine positions in paralogous strains, suggests that
      the sulfide-binding function might have emerged before the annelid radiation in
      order to detoxify this toxic compound. Moreover, globin evolutionary rates are
      highly different between paralogous strains. This suggests that either the two
      globin subfamilies involved in the sulfide-binding function (A2 and B2) have
      evolved under strong directional selective constraints (negative selection) and
      that the two other globins (A1 and B1) have accumulated more substitutions
      through positive selection or have evolved neutrally after a relaxation of
      selection pressures. A likely scenario on the evolution of this multigenic family
      is proposed and discussed from this data set.

PMID- 12200471
TI  - Mitochondrial DNA sequence evolution and phylogeny of the Atlantic Alcidae,
      including the extinct great auk (Pinguinus impennis).
AB  - The Atlantic auk assemblage includes four extant species, razorbill (Alca torda),
      dovekie (Alle alle), common murre (Uria aalge), and thick-billed murre (U.
      lomvia), and one recently extinct species, the flightless great auk (Pinguinus
      impennis). To determine the phylogenetic relationships among the species, a
      contiguous 4.2-kb region of the mitochondrial genome from the extant species was
      amplified using PCR. This region included one ribosomal RNA gene, four transfer
      RNA genes, two protein-coding genes, the control region, and intergenic spacers.
      Sets of PCR primers for amplifying the same region from great auk were designed
      from sequences of the extant species. The authenticity of the great auk sequence
      was ascertained by alternative amplifications, cloning, and separate analyses in
      an independent laboratory. Phylogenetic analyses of the entire assemblage, made
      possible by the great auk sequence, fully resolved the phylogenetic relationships
      and split it into two primary lineages, Uria versus Alle, Alca, and Pinguinus. A
      sister group relationship was identified between Alca and Pinguinus to the
      exclusion of ALLE: Phylogenetically, the flightless great auk originated late
      relative to other divergences within the assemblage. This suggests that three
      highly divergent species in terms of adaptive specializations, Alca, Alle, and
      Pinguinus, evolved from a single lineage in the Atlantic Ocean, in a process
      similar to the initial adaptive radiation of alcids in the Pacific Ocean.

PMID- 12200472
TI  - Analysis of lamprey and hagfish genes reveals a complex history of gene
      duplications during early vertebrate evolution.
AB  - It has been proposed that two events of duplication of the entire genome occurred
      early in vertebrate history (2R hypothesis). Several phylogenetic studies with a
      few gene families (mostly Hox genes and proteins from the MHC) have tried to
      confirm these polyploidization events. However, data from a single locus cannot
      explain the evolutionary history of a complete genome. To study this 2R
      hypothesis, we have taken advantage of the phylogenetic position of the lamprey
      to study the history of gene duplications in vertebrates. We selected most gene
      families that contain several paralogous genes in vertebrates and for which
      lamprey genes and an out-group are known in databases. In addition, we isolated
      members of the nuclear receptor superfamily in lamprey. Hagfish genes were also
      analyzed and found to confirm the lamprey gene analysis. Consistent with the 2R
      hypothesis, the phylogenetic analysis of 33 selected gene families, dispersed
      through the whole genome, revealed that one period of gene duplication arose
      before the lamprey-gnathostome split and this was followed by a second period of
      gene duplication after the lamprey-gnathostome split. Nevertheless, our analysis
      suggests that numerous gene losses and other gene-genome duplications occurred
      during the evolution of the vertebrate genomes. Thus, the complexity of all the
      paralogy groups present in vertebrates should be explained by the contribution of
      genome duplications (2R hypothesis), extra gene duplications, and gene losses.

PMID- 12200473
TI  - Common origin and evolution of glycosyltransferases using Dol-P-monosaccharides
      as donor substrate.
AB  - On the basis of the analysis of 64 glycosyltransferases from 14 species we
      propose that several successive duplications of a common ancestral gene, followed
      by divergent evolution, have generated the mannosyltransferases and the
      glucosyltransferases involved in asparagine-linked glycosylation (ALG) and
      phosphatidyl-inositol glycan anchor (PIG or GPI), which use lipid-related donor
      and acceptor substrates. Long and short conserved peptide motifs were found in
      all enzymes. Conserved and identical amino acid positions were found for the
      alpha 2/6- and the alpha 3/4-mannosyltransferases and for the alpha 2/3
      glucosyltransferases, suggesting unique ancestors for these three superfamilies.
      The three members of the alpha 2-mannosyltransferase family (ALG9, PIG-B, and
      SMP3) and the two members of the alpha 3-glucosyltransferase family (ALG6 and
      ALG8) shared 11 and 30 identical amino acid positions, respectively, suggesting
      that these enzymes have also originated by duplication and divergent evolution.
      This model predicts a common genetic origin for ALG and PIG enzymes using
      dolichyl-phospho-monosaccharide (Dol-P-monosaccharide) donors, which might be
      related to similar spatial orientation of the hydroxyl acceptors. On the basis of
      the multiple sequence analysis and the prediction of transmembrane topology we
      propose that the endoplasmic reticulum glycosyltransferases using Dol-P
      monosaccharides as donor substrate have a multispan transmembrane topology with a
      first large luminal conserved loop containing the long motif and a small
      cytosolic conserved loop containing the short motif, different from the classical
      type II glycosyltransferases, which are anchored in the Golgi by a single
      transmembrane domain.

PMID- 12200474
TI  - Patterns of nucleotide substitution among simultaneously duplicated gene pairs in
      Arabidopsis thaliana.
AB  - We characterized rates and patterns of synonymous and nonsynonymous substitution
      in 242 duplicated gene pairs on chromosomes 2 and 4 of Arabidopsis thaliana.
      Based on their collinear order along the two chromosomes, the gene pairs were
      likely duplicated contemporaneously, and therefore comparison of genetic
      distances among gene pairs provides insights into the distribution of nucleotide
      substitution rates among plant nuclear genes. Rates of synonymous substitution
      varied 13.8-fold among the duplicated gene pairs, but 90% of gene pairs differed
      by less than 2.6-fold. Average nonsynonymous rates were approximately fivefold
      lower than average synonymous rates; this rate difference is lower than that of
      previously studied nonplant lineages. The coefficient of variation of rates among
      genes was 0.65 for nonsynonymous rates and 0.44 for synonymous rates, indicating
      that synonymous and nonsynonymous rates vary among genes to roughly the same
      extent. The causes underlying rate variation were explored. Our analyses
      tentatively suggest an effect of physical location on synonymous substitution
      rates but no similar effect on nonsynonymous rates. Nonsynonymous substitution
      rates were negatively correlated with GC content at synonymous third codon
      positions, and synonymous substitution rates were negatively correlated with
      codon bias, as observed in other systems. Finally, the 242 gene pairs permitted
      investigation of the processes underlying divergence between paralogs. We found
      no evidence of positive selection, little evidence that paralogs evolve at
      different rates, and no evidence of differential codon usage or third position GC
      content.

PMID- 12200475
TI  - Sequence variation and haplotype structure at the putative flowering-time locus
      COL1 of Brassica nigra.
AB  - Motivated by a previous study indicating that polymorphism at an indel, Ind2,
      within the Brassica nigra COL1 gene is significantly associated with flowering
      time, we searched for evidence of selection in a sample of 41 complete sequences
      of B. nigra COL1. The within-gene population recombination rate is moderate, and
      all neutrality tests used in the present study failed to detect departure from
      the standard neutral model or evidence of selection. The haplotype structure of
      the 5'-half of the gene is primarily associated with the demographic history of
      the species and more specifically with the split between European and Ethiopian
      populations, whereas the structure of the 3'-half reflects the polymorphism at
      Ind2. This could be the result of selection or a combination of recombination and
      migration during the history of the sample of sequences. Without additional
      information on polymorphism in flanking areas, these two alternatives are
      difficult to tell apart. If selection acted on the gene, we suggest that if the
      indel itself is not the target of selection, among the polymorphic sites
      cosegregating with the polymorphism at Ind2, replacement polymorphisms around
      sites 890 and 1260 are the most likely quantitative trait nucleotides within the
      gene.

PMID- 12200476
TI  - Recreating a functional ancestral archosaur visual pigment.
AB  - The ancestors of the archosaurs, a major branch of the diapsid reptiles,
      originated more than 240 MYA near the dawn of the Triassic Period. We used
      maximum likelihood phylogenetic ancestral reconstruction methods and explored
      different models of evolution for inferring the amino acid sequence of a putative
      ancestral archosaur visual pigment. Three different types of maximum likelihood
      models were used: nucleotide-based, amino acid-based, and codon-based models.
      Where possible, within each type of model, likelihood ratio tests were used to
      determine which model best fit the data. Ancestral reconstructions of the
      ancestral archosaur node using the best-fitting models of each type were found to
      be in agreement, except for three amino acid residues at which one reconstruction
      differed from the other two. To determine if these ancestral pigments would be
      functionally active, the corresponding genes were chemically synthesized and then
      expressed in a mammalian cell line in tissue culture. The expressed artificial
      genes were all found to bind to 11-cis-retinal to yield stable photoactive
      pigments with lambda(max) values of about 508 nm, which is slightly redshifted
      relative to that of extant vertebrate pigments. The ancestral archosaur pigments
      also activated the retinal G protein transducin, as measured in a fluorescence
      assay. Our results show that ancestral genes from ancient organisms can be
      reconstructed de novo and tested for function using a combination of phylogenetic
      and biochemical methods.

PMID- 12200477
TI  - Identification of essential amino acid changes in paired domain evolution using a
      novel combination of evolutionary analysis and in vitro and in vivo studies.
AB  - Pax genes are defined by the presence of a paired box that encodes a DNA-binding
      domain of 128 amino acids. They are involved in the development of the central
      nervous system, organogenesis, and oncogenesis. The known Pax genes are divided
      into five groups within two supergroups. By means of a novel combination of
      evolutionary analysis, in vitro binding assays and in vivo functional analyses,
      we have identified the key residues that determine the differing DNA-binding
      properties of the two supergroups and of the Pax-2, 5, 8 and Pax-6 subgroups
      within supergroup I. The differences in binding properties between the two
      supergroups are largely caused by amino acid changes at residues 20 and 121 of
      the paired domain. Although the paired domains of the Pax-2, 5, 8 and the Pax-6
      group differ by >19 amino acids, their distinct DNA-binding properties are
      determined almost completely by a single amino acid change. Thus, a small number
      of amino acid changes can account in large part for the divergence in binding
      properties among the known paired domains. Our approach for selecting candidate
      sites responsible for the functional divergence between genes should also be
      useful for studying other gene families.

PMID- 12200478
TI  - Contribution of homoplasy and of ancestral polymorphism to the evolution of genes
      in anthropoid primates.
AB  - Molecular phylogenies of lineages that split from one another in short succession
      are often difficult to resolve because different loci and different sites within
      the same locus yield incongruent relationships. The incongruity is commonly
      attributed to two causes: differential assortment of ancestral polymorphisms and
      homoplasy. To assess the relative contribution of these two causes, sequences of
      57 segments from 51 loci in six primate lineages (human, chimpanzee, gorilla,
      orangutan, macaque, and tamarin, abbreviated as H, C, G, O, M, and T,
      respectively) were subjected to "partitioning" analysis, in which
      phylogenetically informative sites were identified in all 15 pairwise comparisons
      of each of the 57 segments and tallied for their support or lack thereof for each
      of the theoretically possible phylogenies. The six lineages include one of the
      best known cases of a difficult-to-resolve phylogeny: the trichotomy (H, C, G),
      in which the three lineages may have diverged from each other within a short
      period of time. In this period many of the ancestral polymorphisms apparently
      persisted and yielded phylogenetically incongruent signals. By contrast, no
      ancestral polymorphism is expected to have survived during the interval
      separating the divergences of the O, M, and T lineages from the ancestor of the
      (H, C, G) group. Any phylogenetic incompatibilities at sites in the O, M, and T
      lineages relative to the (H, C, G) group are therefore presumably the result of
      homoplasy. The frequency of homoplasy estimated in this manner is unexpectedly
      high: 12% for the (H, C, G) clade and 19% for the (H, C, G, O) clade. At least
      three-quarters of the 48% incompatibility observed in the (H, C) clade is
      attributable to the sorting out of ancestral polymorphisms coupled with
      intragenic recombination. Possible reasons for this high level of homoplasy in
      the O, M, and T lineages are discussed, and a computer simulation has been
      carried out to produce a model explaining the observed data.

PMID- 12200479
TI  - Testing for differences in rates-across-sites distributions in phylogenetic
      subtrees.
AB  - It has long been recognized that the rates of molecular evolution vary amongst
      sites in proteins. The usual model for rate heterogeneity assumes independent
      rate variation according to a rate distribution. In such models the rate at a
      site, although random, is assumed fixed throughout the evolutionary tree. Recent
      work by several groups has suggested that rates at sites often vary across
      subtrees of the larger tree as well as across sites. This phenomenon is not
      captured by most phylogenetic models but instead is more similar to the covarion
      model of Fitch and coworkers. In this article we present methods that can be
      useful in detecting whether different rates occur in two different subtrees of
      the larger tree and where these differences occur. Parametric bootstrapping and
      orthogonal regression methodologies are used to test for rate differences and to
      make statements about the general differences in the rates at sites. Confidence
      intervals based on the conditional distributions of rates at sites are then used
      to detect where the rate differences occur. Such methods will be helpful in
      studying the phylogenetic, structural, and functional bases of changes in
      evolutionary rates at sites, a phenomenon that has important consequences for
      deep phylogenetic inference.

PMID- 12200480
TI  - Kinesin-related genes from diplomonad, sponge, amphioxus, and cyclostomes:
      divergence pattern of kinesin family and evolution of giardial membrane-bounded
      organella.
AB  - To understand the question of whether divergence of eukaryotic genes by gene
      duplications and domain shufflings proceeded gradually or intermittently during
      evolution, we have cloned and sequenced Giardia lamblia cDNAs encoding kinesins
      and kinesin-related proteins and have obtained 13 kinesin-related cDNAs, some of
      which are likely homologs of vertebrate kinesins involved in vesicle transfer to
      ER, Golgi, and plasma membrane. A phylogenetic tree of the kinesin family
      revealed that most gene duplications that gave rise to different kinesin
      subfamilies with distinct functions have been completed before the earliest
      divergence of extant eukaryotes. This suggests that the complex endomembrane
      system has arisen very early in eukaryotic evolution, and the diminutive ER and
      Golgi apparatus recognized in the giardial cells, together with the absence of
      mitochondria, might be characters acquired secondarily during the evolution of
      parasitism. To understand the divergence pattern of the kinesin family in the
      lineage leading to vertebrates, seven more Unc104-related cDNAs have been cloned
      from sponge, amphioxus, hagfish, and lamprey. The divergence pattern of the
      animal Unc104/KIF1 subfamily is characterized by two active periods in gene
      duplication interrupted by a considerably long period of silence, instead of
      proceeding gradually: animals underwent extensive gene duplications before the
      parazoan-eumetazoan split. In the early evolution of vertebrates around the
      cyclostome-gnathostome split, further gene duplications occurred, by which a
      variety of genes with similar structures over the entire regions were generated.
      This pattern of divergence is similar to those of animal genes involved in cell
      cell communication and developmental control.

PMID- 12200481
TI  - Codon and rate variation models in molecular phylogeny.
AB  - This article generalizes previous models for codon substitution and rate
      variation in molecular phylogeny. Particular attention is paid to (1)
      reversibility, (2) acceptance and rejection of proposed codon changes, (3)
      varying rates of evolution among codon sites, and (4) the interaction of these
      sites in determining evolutionary rates. To accommodate spatial variation in
      rates, Markov random fields rather than Markov chains are introduced. Because
      these innovations complicate maximum likelihood estimation in phylogeny
      reconstruction, it is necessary to formulate new algorithms for the evaluation of
      the likelihood and its derivatives with respect to the underlying kinetic,
      acceptance, and spatial parameters. To derive the most from maximum likelihood
      analysis of sequence data, it is useful to compute posterior probabilities
      assigning residues to internal nodes and evolutionary rate classes to codon
      sites. It is also helpful to search through tree space in a way that respects
      accepted phylogenetic relationships. Our phylogeny program LINNAEUS implements
      algorithms realizing these goals. Readers may consult our companion article in
      this issue for several examples.

PMID- 12200482
TI  - Applications of codon and rate variation models in molecular phylogeny.
AB  - The current article illustrates the practical advantages of some new models and
      statistical algorithms for codon substitution and spatial rate variation in
      molecular phylogeny. Our companion paper in this issue discusses at length the
      mathematical properties of these models for nucleotide and codon substitution,
      for site-to-site and branch-to-branch heterogeneity in rates of evolution, and
      for spatial correlation in the assignment of rates. In this study we summarize
      the theoretical background and apply the models and algorithms to data on beta
      globin, the complete HIV genome, and the mitochondrial genome. Our complex but
      realistic models enhance biological interpretation of sequence data and show
      substantial improvements in model fit over existing models. All the new
      statistical algorithms applied are incorporated in our phylogeny software
      LINNAEUS, which is tuned for performance and modeling flexibility.

PMID- 12200483
TI  - GAI homologues in the Hawaiian silversword alliance (Asteraceae-Madiinae):
      molecular evolution of growth regulators in a rapidly diversifying plant lineage.
AB  - Accelerated evolution of regulatory genes has been proposed as an explanation for
      decoupled rates of morphological and molecular evolution. The Hawaiian
      silversword alliance (Asteraceae-Madiinae) has evolved drastic differences in
      growth form, including rosette plants, cushion plants, shrubs, and trees, since
      its origin approximately 6 MYA. We have isolated genes in the DELLA subfamily of
      putative growth regulators from 13 taxa of Hawaiian and North American Madiinae.
      The Hawaiian taxa contain two copies of DaGAI that form separate clades within
      the Madiinae, consistent with an allotetraploid origin for the silversword
      alliance. DaGAI retains conserved features that have previously been identified
      in DELLA genes. Selective constraint in the Hawaiian DaGAI copies remains strong
      in spite of rapid growth form divergence in the silversword alliance, although
      the constraint was somewhat relaxed in the Hawaiian copies relative to the North
      American lineages. We failed to detect evidence for positive selection on
      individual codons. Notably, selective constraint remained especially strong in
      the gibberellin-responsive DELLA region for which the gene subfamily is named,
      which is truncated or deleted in all identified dwarf mutants in GAI homologues
      in different angiosperm species. In contrast with the coding region, however,
      approximately 900 bp of the upstream flanking region shows variable rates and
      patterns of evolution, which might reflect positive selection on regulatory
      regions.

PMID- 12200484
TI  - A strong effect of AT mutational bias on amino acid usage in Buchnera is
      mitigated at high-expression genes.
AB  - The advent of full genome sequences provides exceptionally rich data sets to
      explore molecular and evolutionary mechanisms that shape divergence among and
      within genomes. In this study, we use multivariate analysis to determine the
      processes driving genome-wide patterns of amino usage in the obligate
      endosymbiont Buchnera and its close free-living relative Escherichia coli. In the
      AT-rich Buchnera genome, the primary source of variation in amino acid usage
      differentiates high- and low-expression genes. Amino acids of high-expression
      Buchnera genes are generally less aromatic and use relatively GC-rich codons,
      suggesting that selection against aromatic amino acids and against amino acids
      with AT-rich codons is stronger in high-expression genes. Selection to maintain
      hydrophobic amino acids in integral membrane proteins is a primary factor driving
      protein evolution in E. coli but is a secondary factor in Buchnera. In E. coli,
      gene expression is a secondary force driving amino acid usage, and a correlation
      with tRNA abundance suggests that translational selection contributes to this
      effect. Although this and previous studies demonstrate that AT mutational bias
      and genetic drift influence amino acid usage in Buchnera, this genome-wide
      analysis argues that selection is sufficient to affect the amino acid content of
      proteins with different expression and hydropathy levels.

PMID- 12200485
TI  - The extent of nucleotide polymorphism is highly variable across a 3-kb region on
      Plasmodium falciparum chromosome 2.
AB  - Genomic nucleotide polymorphism in the virulent human malarial parasite
      Plasmodium falciparum was surveyed by sequencing a 3-kb region of chromosome 2
      from 21 isolates, including the MSP4 and MSP5 genes. Extensive sequence
      polymorphism was observed in the coding regions of these genes and in the region
      downstream to MSP5, and the average pairwise divergence time of haplotypes in
      this region was estimated to be at least about 200,000 years. But nucleotide
      polymorphism was not found in the introns and was much reduced in the intergenic
      region. Over the entire region, nucleotide diversity was negatively correlated
      with a nucleotide content skewed toward thymine. Together with the previous
      evidence of limited nucleotide polymorphism in introns of P. falciparum, these
      data suggest the existence of a mechanism suppressing single-nucleotide
      polymorphism in regions of the P. falciparum genome with highly skewed nucleotide
      content.

PMID- 12200486
TI  - Bayesian phylogenetics using an RNA substitution model applied to early mammalian
      evolution.
AB  - We study the phylogeny of the placental mammals using molecular data from all
      mitochondrial tRNAs and rRNAs of 54 species. We use probabilistic substitution
      models specific to evolution in base paired regions of RNA. A number of these
      models have been implemented in a new phylogenetic inference software package for
      carrying out maximum likelihood and Bayesian phylogenetic inferences. We describe
      our Bayesian phylogenetic method which uses a Markov chain Monte Carlo algorithm
      to provide samples from the posterior distribution of tree topologies. Our
      results show support for four primary mammalian clades, in agreement with recent
      studies of much larger data sets mainly comprising nuclear DNA. We discuss some
      issues arising when using Bayesian techniques on RNA sequence data.

PMID- 12200487
TI  - The plastid chromosome of Atropa belladonna and its comparison with that of
      Nicotiana tabacum: the role of RNA editing in generating divergence in the
      process of plant speciation.
AB  - The nuclear and plastid genomes of the plant cell form a coevolving unit which in
      interspecific combinations can lead to genetic incompatibility of compartments
      even between closely related taxa. This phenomenon has been observed for instance
      in Atropa-Nicotiana cybrids. We have sequenced the plastid chromosome of Atropa
      belladonna (deadly nightshade), a circular DNA molecule of 156,688 bp, and
      compared it with the corresponding published sequence of its relative Nicotiana
      tabacum (tobacco) to understand how divergence at the level of this genome can
      contribute to nuclear-plastid incompatibilities and to speciation. It appears
      that (1) regulatory elements, i.e., promoters as well as translational and
      replicational signal elements, are well conserved between the two species; (2)
      genes--including introns--are even more highly conserved, with differences
      residing predominantly in regions of low functional importance; and (3) RNA
      editotypes differ between the two species, which makes this process an intriguing
      candidate for causing rapid reproductive isolation of populations.

PMID- 12200488
TI  - The 5' leader of plant PgiC has an intron: the leader shows both the loss and
      maintenance of constraints compared with introns and exons in the coding region.
AB  - PgiC, a complex gene with 23 coding exons and 22 intervening introns, encodes the
      cytosolic isozyme of phosphoglucose isomerase (EC 5.3.1.9) in higher plants.
      Here, we report RNA ligase-mediated rapid amplification of cDNA ends experiments
      that showed that PgiC in Clarkia (Onagraceae) and Arabidopsis thaliana has an
      intron in the 5' leader. Comparison of the EMBL accessions of the cDNA and
      genomic sequences showed that this is also the case in rice (Oryza sativa),
      suggesting that a leader intron is generally present in higher plant PgiC. The
      intron is bounded by consensus 5'-GT and AG-3' splice sites but showed
      alternative splicing in Clarkia, resulting in mature transcripts that differ by 8
      19 nt in length. The intron is located 18 or 10 nt upstream of the start codon in
      Clarkia, 2 nt upstream in Arabidopsis, and 9 nt in rice. PgiC in Clarkia was
      duplicated before the divergence of the extant species, many of which have two
      expressed genes PgiC1 and PgiC2. Full-length transcripts of both genes identified
      the transcription start and made it possible to identify the leader intron and
      leader exon (between the transcription start and leader intron) from previously
      obtained genomic sequences of both genes in other Clarkia species. These data
      permit the comparison of evolution in the leader exon and intron with the exons
      and introns of the coding region, a topic that has not been studied previously.
      Both the leader exon and the leader intron resemble introns of the coding region
      in base substitution rate and accumulation of gaps. But the leader intron splice
      junctions are not strictly conserved in position as are those of the coding
      region introns. Also, in base composition, the leader intron resembles the other
      introns, whereas the leader exon more nearly resembles the coding exons. A
      difference in base composition between coding exons and flanking introns is known
      to be important for the recognition of splice sites. Thus, the marked difference
      in base composition between the leader exon and leader intron is probably
      maintained by selection despite a high rate of sequence divergence.

PMID- 12200489
TI  - Molecular divergence in the period gene between two putative sympatric species of
      the Lutzomyia longipalpis complex.

PMID- 12200490
TI  - The evolution of the pro-domain of bone morphogenetic protein 4 (Bmp4) in an
      explosively speciated lineage of East African cichlid fishes.

PMID- 12200491
TI  - Molecular evolution of functional genes on the mammalian Y chromosome.

PMID- 12200492
TI  - The paradox of the "ancient" bacterium which contains "modern" protein-coding
      genes.

PMID- 12200493
TI  - The rate of recombination in Wolbachia bacteria.

PMID- 12200496
TI  - Communicating risk: closing the gap between perception and reality.

PMID- 12200497
TI  - Healthy living centers.

PMID- 12200499
TI  - Disasters in urban context.
AB  - This article provides a brief overview of the field of disaster research,
      summarizing what is known at present about the prevalence of disasters, the range
      of stressors and outcomes experienced, and sample-, event-, and individual-level
      risk factors for poor health and mental health outcomes. Prior research does not
      suggest that an urban context either enhances or reduces risk for individual
      survivors. It is argued, however, that the influence of extraindividual exposure,
      ethnic diversity, and support deterioration may be especially salient for
      understanding urban disasters. Investigators of urban disasters are especially
      well situated to expand knowledge of ecological and collective aspects of
      disaster response and recovery.

PMID- 12200500
TI  - Ethical issues in research involving victims of terror.
AB  - Although research after an episode of terror can provide important information to
      improve the health and well-being of present and future victims, there are unique
      ethical challenges that need to be addressed. Man-made disasters have profound
      effects on victims, rescue workers, and their families and on others in the
      community; this may impair their ability to provide voluntary and uncoerced
      decisions about research participation. Because such potential participants in
      research may be vulnerable and also subject to being overburdened with redundant
      research, they deserve special consideration. We propose specific recommendations
      to assist investigators, institutional review boards (IRBs), public health
      officials, and political leaders to help serve the interests of future
      participants in terror-related research.

PMID- 12200501
TI  - Mental health needs in New York state following the September 11th attacks.
AB  - In October 2001, the New York State Office of Mental Health and the Department of
      Epidemiology of the Mailman School of Public Health of Columbia University
      conducted a rapid assessment of the nature and magnitude of mental health needs
      in the state resulting from the September 11th terrorist attacks on the World
      Trade Center. This effort was carried out during a period of great turmoil and
      uncertainty as New Yorkers responded to the shocking events of this unprecedented
      disaster. Using the limited data available at the time, we estimated that over
      520,000 persons in New York City and the surrounding counties would experience
      posttraumatic stress disorder resulting from exposure to the attacks, and that
      more than 129,000 would seek treatment for this disorder during 2002. This
      assessment is part of an ongoing collaborative process between public and
      academic partners; the effort is designed to strengthen the capacity of the
      mental health system to respond to current and future terrorism. Estimates from
      this initial assessment will be refined over time as further data concerning the
      impact of the September 11th attacks become available.

PMID- 12200502
TI  - The public costs of mental health response: lessons from the New York City post
      9/11 needs assessment.
AB  - There is evidence of increased rates of psychiatric disorder in New York City in
      the period following September 11th. Public mental health services need to
      develop plans to respond to these higher rates of disorder. This article
      describes what we know and do not know with respect to the costs of such
      response. We examine evidence on the demand for mental health services, the
      nature of services to be provided, the characteristics of providers, and the
      likely sources of payment for care in the context of the attacks of September
      11th in New York City.

PMID- 12200503
TI  - Posttraumatic stress disorder in Manhattan, New York City, after the September
      11th terrorist attacks.
AB  - Estimates of acute mental health symptoms in the general population after
      disasters are scarce. We assessed the prevalence and correlates of acute
      posttraumatic stress disorder (PTSD) in residents of Manhattan 5-8 weeks after
      the terrorist attacks of September 11, 2001. We used random-digit dialing to
      contact a representative sample of adults living in Manhattan below 110th Street.
      Participants were interviewed about prior life events, personal characteristics,
      exposure to the events of September 11th, and psychological symptoms after the
      attack. Among 988 eligible adults, 19.3% reported symptoms consistent with PTSD
      at some point in their life, and 8.8% reported symptoms consistent with a
      diagnosis of current (within the past 30 days) PTSD. Overall, 57.8% of
      respondents reported at least one PTSD symptom in the past month. The most common
      past-month symptoms were intrusive memories (27.4%) and insomnia (24.5%).
      Predictors of current PTSD in a multivariable model were residence below Canal
      Street, low social support, life stressors 12 months prior to September 11th,
      perievent panic attack, losing possessions in the attacks, and involvement in the
      rescue efforts. These findings can help guide resource planning for future
      disasters in densely populated urban areas.

PMID- 12200505
TI  - The impact of the 1995 Oklahoma City bombing on the partners of firefighters.
AB  - This study explored the impact of the 1995 Oklahoma City, Oklahoma, bombing on
      the spouses and significant others of a volunteer sample of Oklahoma City
      firefighters who participated in the bombing rescue effort. Twenty-seven partners
      of Oklahoma City firefighters participated in this study, conducted 42 to 44
      months after the bombing. These partners were assessed using a structured
      diagnostic interview and a companion interview to examine exposure, rates of
      psychiatric disorders and symptoms, functioning, health, and relationships.
      Coping and perception of the firefighter partner's response were also examined.
      Some of the women were exposed directly; most knew someone who had been involved
      in the disaster, and all reported exposure through the media. The rate of
      psychiatric disorders in the women following the disaster was 22%, essentially
      unchanged from before the incident. One developed bomb-related posttraumatic
      stress disorder (PTSD). Most were satisfied with their work performance; 15%
      reported that their health had worsened since the bombing, and more than one
      third reported permanent changes in relationships as a result of the bombing.
      Most coped by turning to friends or relatives, with less than 10% seeking
      professional help. Many described symptoms in their firefighter mate; all
      reported that their mate had been affected by the experience, and one half said
      their mate had fully recovered. The mates of these firefighters fared relatively
      well in terms of psychiatric disorders, symptoms, and ability to function. The
      prevalence of bomb-related posttraumatic stress disorder was considerably lower
      in this sample than in samples of individuals more directly exposed to the
      bombing, although some reported changes in relationships and health. The results
      suggest the need for further study of the impact of interpersonal exposure in
      those who provide support for rescue-and-recovery workers in major terrorist
      incidents.

PMID- 12200504
TI  - Exposure and peritraumatic response as predictors of posttraumatic stress in
      children following the 1995 Oklahoma City bombing.
AB  - Studies have demonstrated a positive relationship between exposure and
      posttraumatic stress, but one's subjective appraisal of danger and threat at the
      time of exposure may be a better predictor of posttraumatic stress than more
      objective measures of exposure. We examined the role of peritraumatic response in
      posttraumatic stress reactions in over 2,000 middle school children 7 weeks after
      the 1995 Oklahoma City, Oklahoma, bombing. While many children reported hearing
      and feeling the blast and knowing direct victims, most were in school at the time
      of the explosion and therefore were not in direct physical proximity to the
      incident. Physical, interpersonal, and television exposure accounted for 12% of
      the total variance in our measure of posttraumatic stress when peritraumatic
      response was ignored. Peritraumatic response and television exposure accounted
      for 25% of the total variance, and physical and interpersonal exposure were not
      significant in this context. These findings suggest the importance of
      peritraumatic response in children's reactions to terrorism. These early
      responses can be used to help determine which children may experience difficulty
      over time.

PMID- 12200506
TI  - Risk factors for depression in the survivors of the 1988 earthquake in Armenia.
AB  - Most studies of psychopathology following disasters are concerned with
      posttraumatic stress disorder (PTSD). The present analyses sought to assess the
      rate and determinants of depression in adult survivors of the 1988 earthquake in
      Armenia. Unlike previous studies of earthquakes, the present analyses derive from
      a well-defined cohort of survivors who underwent diagnostic interviewing to
      characterize psychiatric morbidity. As part of a cohort study of 32,743 survivors
      of the 1988 earthquake in Armenia, a stratified population sample of 1,785
      persons was interviewed about 2 years following the disaster using a special
      questionnaire based on the National Institute of Mental Health (NIMH) Disaster
      Interview Schedule/Disaster Supplement. 52% met the criteria for major
      depression. Of these, a total of 177 cases of depression with no other
      psychiatric diagnosis or comorbidity were compared with 583 controls from the
      same interviewed group who did not fulfill the criteria for any psychiatric
      disorder. Cases and controls were compared as to data obtained independently at
      the aftermath of the disaster on a number of exposures and characteristics
      related to the earthquake. More of the cases involved females (odds ratio [OR]
      for males 0.7 [95% confidence interval [CI] 0.5-0.9]) and from the city of Gumri,
      which had some of the worst destruction (OR for residents of Gumri 5.9 [95% CI
      4.0-8.8]). Being with someone in the same building at the moment of the
      earthquake was protective for depression (OR for presence of other people 0.5
      [95% CI 0.3-0.6]), and the risk of depression increased with the amount of loss
      that the family sustained as a result of the earthquake (OR for highest level of
      loss 2.5 [95% CI 1.3-4.8]). The use of alcohol was protective for depression (OR
      for those who drink 0.5 [95% CI 0.3-0.8]). In various models of multivariate
      adjustment and analysis, the increased risk of depression with loss, geographic
      location, and female gender was maintained. Also, being with someone during the
      disaster, receiving assistance and support after the earthquake, and alcohol use
      were protective for depression in these multivariate analyses. Depression is a
      common sequel to an earthquake. As with our previous study of PTSD, we were able
      to relate intensity of the disaster and loss to the risk of depression in a
      general population sample. The role of social support during and after the
      disaster as a protective mechanism against adverse psychological outcome was
      highlighted again. Whereas alcohol use in our previous study was not related to
      PTSD outcome, it is noteworthy that in the present analyses it emerged as a
      protective factor for depression.

PMID- 12200507
TI  - Three-year follow-up of survivors of a mass shooting episode.
AB  - This report describes a 3-year follow-up study of survivors of a mass shooting
      incident. Acute-phase and 1-year follow-up data from this incident have been
      previously reported. The Diagnostic Interview Schedule/Disaster Supplement was
      used to assess 116 survivors at 1-2 months and again 1 and 3 years later, with an
      85% reinterview rate. Examining the course of postdisaster posttraumatic stress
      disorder (PTSD) and major depression in individuals allowed detailed
      consideration of remissions and delayed detection of disorders not possible from
      data presenting overall rates across different time frames. Only about one half
      of the PTSD cases identified at any time over 3 years were in remission at the 3
      year follow-up. Those who did not recover from PTSD diverged from those who
      recovered at 3 years by reporting increased numbers of symptoms over time,
      especially avoidance and numbing symptoms. Although women and people with
      preexisting disorders were at greater risk for the development of PTSD, these
      variables did not predict chronicity. Chronicity of PTSD was predicted by
      functional impairment and seeking mental health treatment at baseline. Chronicity
      of major depression was predicted by report of family history of depression and
      treatment for paternal alcohol problems. No delayed cases of PTSD were
      identified. Studies are needed to compare these characteristics of the course of
      PTSD with other populations, using consistent methodology to allow valid
      comparison.

PMID- 12200508
TI  - A vulnerable population in a time of crisis: drug users and the attacks on the
      World Trade Center.
AB  - In this article, we present preliminary findings from a qualitative study focused
      on the impact of the World Trade Center attacks on New York City residents who
      are current or former users of heroin, crack, and other forms of cocaine. In it,
      we present data describing their responses to and feelings about the attacks,
      changes in drug use after the attacks, and factors affecting changes in use. Our
      analysis is based on 57 open-ended interviews conducted between October 2001 and
      February 2002. The majority of study participants reported that the attacks had a
      significant emotional impact on them, causing anxiety, sadness, and anger.
      Several described practical impacts as well, including significant reductions in
      income. On September 11th and the weeks and months that followed, several
      participants who had been actively using did increase their use of heroin, crack,
      and/or other forms of cocaine. Reductions in use were, however, as common over
      time as were increases. There was some relapse among former users, but this was
      limited to those who had stopped using drugs within the 6 months immediately
      preceding the attacks. A diverse set of factors interacted to control use. For
      some participants, these factors were internal, relating to their individual
      motivations and drug use experiences. Other participants were essentially forced
      to limit use by marked reductions in income. For others, access to health and
      social service professionals, as well as drug treatment, proved to be key.

PMID- 12200509
TI  - Drug use frequency among street-recruited heroin and cocaine users in Harlem and
      the Bronx before and after September 11, 2001.
AB  - We determined if illicit drug use frequency changes after a disaster by comparing
      drug use frequency in two street-recruited samples of heroin and cocaine users,
      ages 15-40 years. The users were interviewed between July 11 and November 11 and
      divided into before- and after-September 11th groups for analysis. The before and
      after groups were similar in the mean number of days of drug use per month (sniff
      cocaine 6.8 days vs. 9.4 days, respectively, P =.17; snorted heroin 13.9 vs.
      14.0, respectively, P =.96; smoked crack 16.9 vs. 15.6, respectively, P =.96; and
      smoked marijuana 17.5 vs. 15.3, respectively, P =.36) and in the proportion of
      daily users: sniffed cocaine 10% versus 17%, respectively (P =.28); snorted
      heroin 47% versus 40%, respectively (P =.91); smoked crack 33% versus 37%,
      respectively (P =.68); and smoked marijuana 47% versus 40%, respectively (P
      =.41). Among street-recruited heroin and cocaine users in Harlem and the Bronx,
      the frequency of drug use did not increase following the events of September 11,
      2001.

PMID- 12200510
TI  - Impact of the September 11th attacks in New York City on drug users: a
      preliminary assessment.
AB  - An exploratory assessment of the impact of the September 11th attacks in New York
      City on drug users, including their perceptions of changes in drug use, drug
      availability, police activities, and access to services, was undertaken. Methods
      included focus groups with drug users and acquired immunodeficiency syndrome
      (AIDS) outreach worker supervisors and surveys of service providers. Results
      indicated that, while there was some immediate concern about the potential impact
      on drug availability, there was no perceived scarcity, although some drug users
      did report a decrease in drug purity. Responses included increased use of drugs
      and increased demand for drug treatment. The wide range of responses indicates
      that continued monitoring of the impact may be needed to assess long-term
      effects.

PMID- 12200511
TI  - Emergency preparedness training for public health nurses: a pilot study.
AB  - The Columbia Center for Public Health Preparedness, in partnership with the New
      York City Department of Health, recently developed an emergency preparedness
      training program for public health workers. A pilot training program was
      conducted for a group of school health nurses and evaluated using a pre/posttest
      design. A surprising finding was that 90% of the nurses reported at least one
      barrier to their ability to report to duty in the event of a public health
      emergency. The most frequently cited barriers included child/elder care
      responsibilities, lack of transportation, and personal health issues. These
      findings suggest that it may be prudent to identify and address potential
      barriers to public health workforce responsiveness to ensure the availability of
      the workforce during emergencies.

PMID- 12200512
TI  - Calls for help after September 11: a community mental health hot line.
AB  - Although unprepared for a disaster of the magnitude of September 11th, New York
      City's mental health system responded immediately. Within weeks, Project Liberty,
      a recovery program funded by the Federal Emergency Management Agency (FEMA), was
      in operation. The program provides free education, outreach, and crisis
      counseling services for those affected by the disaster and its aftermath.
      LifeNet, a 24-hour, 7-day-a-week mental health information and referral hotline,
      is a key component of Project Liberty. In this article, we describe the operation
      of LifeNet and examine the volume of calls to the hotline during the 6 months
      following the terrorist attacks on the World Trade Center. We describe the
      demographics of the callers and the kinds of disaster-related mental health
      problems that callers presented. The data indicate a clear pattern of increasing
      calls from October through March for all demographic subgroups except seniors.
      Callers complaining of symptoms of posttraumatic stress and symptoms of anxiety,
      panic, and phobia increased over time. Bereavement-related calls increased as
      well. The number of callers who reported symptoms of depression and substance
      abuse/dependence did not show as clear-cut an increase over time. We looked at
      the volume of LifeNet calls in relation to the Project Liberty media campaign and
      suggest that the campaign has had a positive effect on call volume and that its
      impact is likely to continue over time.

PMID- 12200513
TI  - Project Liberty: a public health response to New Yorkers' mental health needs
      arising from the World Trade Center terrorist attacks.
AB  - The September 11th terrorist attacks had a dramatic impact on the mental health
      of millions of Americans. The impact was particularly severe in New York City and
      surrounding areas within commuting distance of the World Trade Center. With
      support from the federal government, state and local mental health authorities
      rapidly mounted a large-scale public health intervention aimed at ameliorating
      the traumatic stress experienced by residents of the disaster area. The resulting
      program, named Project Liberty, has provided free public educational and crisis
      counseling services to tens of thousands of New Yorkers in its initial months of
      operation. Individuals served vary widely in the severity of experienced trauma
      and associated traumatic reactions. Data from logs kept by Project Liberty
      workers suggest that individuals with the most severe reactions are being
      referred to longer-term mental health treatment services.

PMID- 12200514
TI  - Population impact of mass incarceration under New York's Rockefeller drug laws:
      an analysis of years of life lost.

PMID- 12200515
TI  - Exacerbations of chronic obstructive pulmonary disease.

PMID- 12200516
TI  - Gene expression profiling: good housekeeping and a clean message.

PMID- 12200517
TI  - Psychological consequences of segregation resulting from chronic Burkholderia
      cepacia infection in adults with CF.

PMID- 12200518
TI  - Relationship between bacterial colonisation and the frequency, character, and
      severity of COPD exacerbations.
AB  - BACKGROUND: Patients with chronic obstructive pulmonary disease (COPD) are prone
      to frequent exacerbations which are a significant cause of morbidity and
      mortality. Stable COPD patients often have lower airway bacterial colonisation
      which may be an important stimulus to airway inflammation and thereby modulate
      exacerbation frequency. METHODS: Twenty nine patients with COPD (21 men, 16
      current smokers) of mean (SD) age 65.9 (7.84) years, forced expiratory volume in
      1 second (FEV(1)) 1.06 (0.41) l, FEV(1) % predicted 38.7 (15.2)%, FEV(1)/FVC 43.7
      (14.1)%, inhaled steroid dosage 1.20 (0.66) mg/day completed daily diary cards
      for symptoms and peak flow over 18 months. Exacerbation frequency rates were
      determined from diary card data. Induced sputum was obtained from patients in the
      stable state, quantitative bacterial culture was performed, and cytokine levels
      were measured. RESULTS: Fifteen of the 29 patients (51.7%) were colonised by a
      possible pathogen: Haemophilus influenzae (53.3%), Streptococcus pneumoniae
      (33.3%), Haemophilus parainfluenzae (20%), Branhamella catarrhalis (20%),
      Pseudomonas aeruginosa (20%). The presence of lower airway bacterial colonisation
      in the stable state was related to exacerbation frequency (p=0.023). Patients
      colonised by H influenzae in the stable state reported more symptoms and
      increased sputum purulence at exacerbation than those not colonised. The median
      (IQR) symptom count at exacerbation in those colonised by H influenzae was 2.00
      (2.00-2.65) compared with 2.00 (1.00-2.00) in those not colonised (p=0.03). The
      occurrence of increased sputum purulence at exacerbation per patient was 0.92
      (0.56-1.00) in those colonised with H influenzae and 0.33 (0.00-0.60) in those
      not colonised (p=0.02). Sputum interleukin (IL)-8 levels correlated with the
      total bacterial count (rho=0.459, p=0.02). CONCLUSION: Lower airway bacterial
      colonisation in the stable state modulates the character and frequency of COPD
      exacerbations.

PMID- 12200519
TI  - beta-Actin and GAPDH housekeeping gene expression in asthmatic airways is
      variable and not suitable for normalising mRNA levels.
AB  - BACKGROUND: The use of reverse transcription-polymerase chain reaction (RT-PCR)
      to measure mRNA levels has led to the common use of beta-actin and GAPDH
      housekeeping genes as denominators for comparison of samples. Expression of these
      genes is assumed to remain constant, so normalising for variations in processing
      and signal quantitation. However, it is well documented that beta-actin and GAPDH
      expression is upregulated with proliferation, activation, and differentiation. We
      hypothesised that airway samples which differ in their cellular profiles and
      activation status have different levels of expression of GAPDH and beta-actin.
      METHODS: The mRNA for beta-actin, GAPDH, and interleukin (IL)-2 was measured in
      bronchoalveolar lavage (BAL) fluid cells and endobronchial biopsy tissue by
      competitive RT-PCR in a cross sectional study of 26 normal controls and 92
      asthmatic subjects. RESULTS: For both BAL fluid cells and biopsy tissue,
      asthmatics overall had reduced expression of GAPDH and beta-actin mRNA. In
      asthmatic subjects not using inhaled corticosteroids (ICS), GAPDH mRNA levels in
      both BAL fluid and biopsy tissue, and beta-actin mRNA in BAL fluid cells were 10
      times lower than samples from both normal controls and from asthmatic subjects
      using ICS. beta-Actin mRNA in biopsy specimens showed the same pattern of
      expression, but asthmatic subjects not using ICS were not significantly different
      from those receiving ICS treatment. IL-2 mRNA levels did not differ between the
      subject or treatment groups but, when expressed as a ratio with beta-actin,
      significant differences were seen. CONCLUSIONS: beta-Actin and GAPDH used as
      denominators of gene expression quantitation in asthma research can cause
      confounding. Housekeeping genes need careful validation before their use in such
      quantitative mRNA assays.

PMID- 12200520
TI  - Reduction in exhaled nitric oxide immediately after methacholine challenge in
      asthmatic children.
AB  - BACKGROUND: The measurement of exhaled nitric oxide (NO) has recently been
      proposed as a useful technique for the evaluation of airway inflammation in
      asthma. The purpose of this study was to determine the effect of methacholine
      bronchial provocation on the levels of exhaled NO in asthmatic children. METHOD:
      Exhaled NO was measurement immediately before and after methacholine provocation
      in 51 children with mild to moderate asthma. RESULTS: A significant decrease
      occurred in the level of exhaled NO (p<0.0001) after methacholine bronchial
      provocation which was not correlated with the percentage fall in forced
      expiratory volume in 1 second (FEV(1)). CONCLUSIONS: The methacholine test should
      not be used immediately before measurement of exhaled NO in children with asthma.

PMID- 12200521
TI  - Effects of inhaled tumour necrosis factor alpha in subjects with mild asthma.
AB  - BACKGROUND: Inhaled tumour necrosis factor alpha (TNF alpha) has previously been
      shown to induce airway neutrophilia and increased airway reactivity in normal
      subjects. It was hypothesised that a similar challenge would increase airway
      reactivity in those with mild asthma, but that the inflammatory profile may
      differ. METHODS: Ten mild asthmatic subjects were recruited on the basis of
      clinical asthma and either a sensitivity to methacholine within the range defined
      for asthma or a 20% improvement in forced expiratory volume (FEV(1)) after 200
      micro g salbutamol. Subjects inhaled either vehicle control or 60 ng recombinant
      human (rh)TNF alpha and were studied at baseline, 6, 24, and 48 hours later.
      Variables included spirometric parameters, methacholine provocative concentration
      causing a 20% fall in FEV(1) (PC(20)), induced sputum differential cell count,
      relative sputum level of mRNA of interleukins (IL)-4, IL-5, IL-9, IL-14, IL-15
      and TNF alpha, and the exhaled gaseous markers of inflammation, nitric oxide and
      carbon monoxide. RESULTS: PC(20) showed an increase in sensitivity after TNF
      alpha compared with control (p<0.01). The mean percentage of neutrophils
      increased at 24-48 hours (24 hour control: 1.1 (95% CI 0.4 to 2.7) v 9.2 (95% CI
      3.5 to 14.9), p<0.05), and there was also a rise in eosinophils (p=0.05).
      Relative levels of sputum mRNA suggested a rise in expression of TNF alpha, IL
      14, and IL-15, but no change in IL-4 and IL-5. Spirometric parameters and exhaled
      gases showed no significant change. CONCLUSION: The increase in airway
      responsiveness and sputum inflammatory cell influx in response to rhTNF alpha
      indicates that TNF alpha may contribute to the airway inflammation that
      characterises asthma.

PMID- 12200522
TI  - Increased blood carboxyhaemoglobin concentrations in inflammatory pulmonary
      diseases.
AB  - BACKGROUND: Exhaled carbon monoxide has been reported to increase in inflammatory
      pulmonary diseases and to be correlated with blood carboxyhaemoglobin (Hb-CO)
      concentration. A study was undertaken to determine whether arterial blood Hb-CO
      increases in patients with inflammatory pulmonary diseases. METHODS: The Hb-CO
      concentration in arterial blood was measured with a spectrophotometer in 34
      normal control subjects, 24 patients with bronchial asthma, 52 patients with
      pneumonia, and 21 patients with idiopathic pulmonary fibrosis (IPF). RESULTS: The
      mean (SE) Hb-CO concentrations in patients with bronchial asthma during
      exacerbations (n=24, 1.05 (0.05)%), with pneumonia at the onset of illness (n=52,
      1.08 (0.06)%), and with IPF (n=21, 1.03 (0.09)%) were significantly higher than
      those in control subjects (n=34, 0.60 (0.07)%) (mean difference 0.45% (95%
      confidence interval (CI) 0.23 to 0.67), p<0.01 in patients with bronchial asthma,
      mean difference 0.48% (95% CI 0.35 to 0.60), p<0.0001 in patients with pneumonia,
      and mean difference 0.43% (95% CI 0.26 to 0.61) p<0.001 in patients with IPF). In
      20 patients with bronchial asthma the Hb-CO concentration decreased after 3 weeks
      of treatment with oral glucocorticoids (p<0.001). In 20 patients with pneumonia
      the Hb-CO concentration had decreased after 3 weeks when patients showed evidence
      of clinical improvement (p<0.001). The values of C-reactive protein (CRP), an
      acute phase protein, correlated with Hb-CO concentrations in patients with
      pneumonia (r=0.74, p<0.0001) and in those with IPF (r=0.46, p<0.01). In patients
      with bronchial asthma changes in Hb-CO concentrations were significantly
      correlated with those in forced expiratory volume in 1 second (FEV(1)) after 3
      weeks (r=0.67, p<0.01). Exhaled carbon monoxide (CO) concentrations were
      correlated with Hb-CO concentrations (n=33, r=0.80, p<0.0001). CONCLUSIONS: Hb-CO
      concentrations are increased in inflammatory pulmonary diseases including
      bronchial asthma, pneumonia, and IPF. Measurement of arterial Hb-CO may be a
      useful means of monitoring pulmonary inflammation.

PMID- 12200523
TI  - Clinical evaluation of the effect of anti-allergic mattress covers in patients
      with moderate to severe asthma and house dust mite allergy: a randomised double
      blind placebo controlled study.
AB  - BACKGROUND: The use of anti-allergic mattress covers in patients with asthma can
      result in a large reduction in the level of house dust mite allergen in dust
      samples. Apart from a reduction in histamine induced bronchial
      hyperresponsiveness, there are few data on the effect of mattress covers on
      clinical efficacy and quality of life in patients with moderate to severe asthma.
      METHODS: Thirty patients with asthma and house dust mite allergy were studied in
      a randomised, double blind, placebo controlled study. Before and after using anti
      allergic covers for 1 year, dust was collected from the mattresses to determine
      concentrations of Dermatophagoides pteronyssinus (Der p 1), and bronchial
      hyperresponsiveness and quality of life were measured. The patients scored their
      symptoms (lungs and nose), morning and evening peak flow values, and rescue
      medication for 14 days before and after the intervention period. RESULTS: There
      was a significant reduction in the concentration of Der p 1 in the dust collected
      from the mattresses in the actively treated group after 1 year compared with
      before treatment; no change was found in the placebo group. In both the actively
      treated and placebo groups there was no significant improvement in PC(20)
      histamine. Quality of life improved similarly in both groups. The symptom score
      of the lower airways did not significantly change in either group. A significant
      decrease in nasal symptom score was seen in the actively treated group compared
      with before treatment, but there was no significant difference between the
      groups. No changes in morning and evening peak flow values, peak flow
      variability, nor in the use of rescue medication were found in either group.
      CONCLUSION: The use of anti-allergic mattress covers results in significant
      reductions in Der p 1 concentrations in carpet-free bedrooms. However, in
      patients with moderate to severe asthma, airways hyperresponsiveness and clinical
      parameters are not affected by this effective allergen avoidance.

PMID- 12200524
TI  - Early asthma control and maintenance with eformoterol following reduction of
      inhaled corticosteroid dose.
AB  - BACKGROUND: Previous studies have indicated the benefits of adding long acting
      beta(2) agonists to inhaled corticosteroids in the maintenance treatment of
      moderate to severe asthma. The effects of adding eformoterol to corticosteroids
      on asthma control and exacerbations in patients with mild to moderate asthma were
      studied. METHODS: After a run in period of 7-14 days on existing medication, 663
      symptomatic patients were randomised to receive budesonide Turbohaler 400 microg
      twice daily together with either eformoterol Turbohaler 9 micro g (delivered
      dose) or placebo twice daily. After 4 weeks patients whose asthma was well
      controlled (n=505) were re-randomised to receive budesonide 400 microg daily and
      either eformoterol 9 micro g or placebo twice daily for a further 6 months.
      RESULTS: Patients receiving eformoterol achieved asthma control 10 days sooner
      than those receiving budesonide alone, and improvements in lung function,
      symptoms, quality of life, and relief beta(2) agonist use were significantly
      greater with eformoterol. During the 6 month follow up the frequency of mild
      exacerbations was significantly lower in the eformoterol group than in those
      receiving budesonide alone (7.2 versus 10.5 per patient, 95% confidence interval
      for ratio 0.49 to 0.96, p=0.03). The time to first day of poorly controlled
      asthma was 97 days in the eformoterol group compared with 42 days in the placebo
      group (p=0.003). CONCLUSIONS: Adding eformoterol to a low or moderate dose of
      budesonide in mild asthma resulted in faster and more effective control than
      treatment with budesonide alone. Eformoterol allowed the corticosteroid dose to
      be reduced while also decreasing the rate of mild exacerbations compared with
      budesonide alone. These data suggest a therapeutic advantage of adding
      eformoterol to inhaled corticosteroids in patients with mild to moderate asthma.

PMID- 12200525
TI  - Effects of fluticasone propionate on inflammatory cells in COPD: an
      ultrastructural examination of endobronchial biopsy tissue.
AB  - BACKGROUND: Inhaled corticosteroids (ICS) markedly reduce bronchial mucosal
      inflammation in asthma but whether they have an anti-inflammatory effect in
      airway tissue in chronic obstructive pulmonary disease (COPD) is unknown.
      METHODS: A study of endobronchial biopsy samples was conducted as part of a
      double blind, placebo controlled, randomised trial of parallel design. Patients
      had mild to moderately severe COPD (FEV(1) 25-80% of predicted) and were given 3
      months treatment with ICS, fluticasone propionate (FP; 500 micro g twice daily,
      n=14) or placebo (n=10). Biopsy tissue taken at baseline and after treatment was
      examined by transmission electron microscopy to count the numbers of all
      ultrastructurally distinct inflammatory cells. RESULTS: Compared with their
      baseline values, FP resulted in a significant decrease (on average 65%) in the
      numbers of mucosal mast cells (median 7.8 (range 1-33) v 2.8 (1-14), p<0.05). The
      reductive effect of FP held true when the post-treatment values of the placebo
      and FP groups were compared: 8.8 (1-24) v 2.8 (1-14) (p<0.05). Unexpectedly,
      there were significantly more neutrophils in the FP than in the placebo group:
      4.0 (0-23) v 1.7 (0-8), respectively (p<0.05). There were no alterations to other
      cell types including mononuclear cells. Symptoms markedly improved in the
      patients treated with FP for 3 months. CONCLUSION: Fluticasone propionate given
      for 3 months to patients with COPD has selective effects on the inflammatory
      cells in the bronchial mucosa: the reduction in mast cell numbers may account for
      the improvement in symptoms over this time.

PMID- 12200526
TI  - A meta-analysis of the effect of Bacille Calmette Guerin vaccination on
      tuberculin skin test measurements.
AB  - BACKGROUND: The accurate diagnosis of latent tuberculosis infection (LTBI) is an
      important component of any tuberculosis control programme and depends largely on
      tuberculin skin testing. The appropriate interpretation of skin test results
      requires knowledge of the possible confounding factors such as previous BCG
      vaccination. Uncertainty about the effect of BCG vaccination on tuberculin skin
      testing and the strength with which recommendations are made to individual
      patients regarding treatment of LTBI have identified a need to analyse the
      available data on the effect of BCG on skin testing. A meta-analysis of the
      evidence for the effect of BCG vaccination on tuberculin skin testing in subjects
      without active tuberculosis was therefore performed. METHODS: Medline was
      searched for English language articles published from 1966 to 1999 using the key
      words "BCG vaccine", "tuberculin test/PPD", and "skin testing". Bibliographies of
      relevant articles were reviewed for additional studies that may have been missed
      in the Medline search. Articles were considered for inclusion in the meta
      analysis if they had recorded tuberculin skin test results in subjects who had
      received BCG vaccination more than 5 years previously and had a concurrent
      control group. Only prospective studies were considered. The geographical
      location, number of participants, type of BCG vaccine used, type of tuberculin
      skin test performed, and the results of the tuberculin skin test were extracted.
      RESULTS: The abstracts and titles of 980 articles were identified, 370 full text
      articles were reviewed, and 26 articles were included in the final analysis.
      Patients who had received BCG vaccination were more likely to have a positive
      skin test (5 TU PPD: relative risk (RR) 2.12 (95% confidence interval (CI)1.50 to
      3.00); 2 TU RT23: 2.65 [corrected] (95% CI 1.83 to 3.85). The effect of BCG
      vaccination on PPD skin test results was less after 15 years. Positive skin tests
      with indurations of >15 mm are more likely to be the result of tuberculous
      infection than of BCG vaccination. CONCLUSIONS: In subjects without active
      tuberculosis, immunisation with BCG significantly increases the likelihood of a
      positive tuberculin skin test. The interpretation of the skin test therefore
      needs to be made in the individual clinical context and with evaluation of other
      risk factors for infection. The size of the induration should also be considered
      when making recommendations for treatment of latent infection.

PMID- 12200527
TI  - A national study of clinical and laboratory factors affecting the survival of
      patients with multiple drug resistant tuberculosis in the UK.
AB  - BACKGROUND: This study aimed to describe the clinical, microbiological, molecular
      epidemiology and treatment of multidrug resistant tuberculosis (MDRTB) cases in
      the UK and to determine factors associated with survival. METHODS: Ninety MDRTB
      cases were identified from 1 January 1996 to 30 June 1997; 69 were DNA
      fingerprinted. Date of diagnosis was determined and data were collated on key
      demographic factors, clinical, radiological and treatment details. Variables
      associated with survival were included in a Cox proportional hazards model.
      RESULTS: Most of the patients (72.4%) were male, born outside the UK (57.1%),
      were sputum smear positive (82.2%), and had entered the UK more than 5 years
      previously (61.9%). Thirty eight of 78 cases (48.7%) had prior TB. Sufficient
      data on 82 patients were available for survival analysis; 20/27 (74.1%) known to
      be dead at the end of the observation period had died of tuberculosis. Median
      survival time overall was 1379 days (95% CI 1336 to 2515) or 3.78 (95% CI 3.66 to
      6.89) years (858 days (95% CI 530 to 2515) in immunocompromised individuals
      (n=32) and 1554 (95% CI 1336 to 2066) days in immunocompetent cases (n=48)).
      Median survival in patients treated with three drugs to which the bacterium was
      susceptible on in vitro testing (n=62) was 2066 days (95% CI 1336 to 2515) or
      5.66 years, whereas in those not so treated (n=13) survival was 599 days (95% CI
      190 to 969) or 1.64 years. CONCLUSIONS: Immunocompromised status, failure to
      culture the bacterium in 30 days or to apply appropriate three drug treatment,
      and age were significant factors in mortality. An immunocompromised patient was
      nearly nine times more likely to die, while application of appropriate treatment
      reduced the risk (risk ratio 0.06). Increasing age was associated with increasing
      risk of death (risk ratio 2.079; 95% CI 1.269 to 3.402)-that is, for every 10
      year increase in age the risk almost doubled. Overall survival was lower than
      that reported in previous studies.

PMID- 12200528
TI  - Management of solitary pulmonary nodules: how do thoracic computed tomography and
      guided fine needle biopsy influence clinical decisions?
AB  - BACKGROUND: Computed tomography (CT) and fine needle guided biopsy (FNB) are
      often used in the assessment of patients with lung nodules. The influence of
      these techniques on clinical decision making has not been quantified, especially
      for small solitary pulmonary nodules (SPN) where the probability of malignancy is
      lower. A study was undertaken to determine the effect of CT and FNB derived
      information on clinical decision making in patients with a solitary pulmonary
      nodule < or = 3 cm in diameter on initial chest radiography. METHODS: Clinical,
      physiological, and outcome data on 114 patients with an SPN < or = 3 cm who had
      subsequent thoracic CT and FNB were extracted from the records of a specialist
      cardiorespiratory hospital in Auckland, New Zealand. Chest radiographs and CT
      scans were reported according to specified criteria by a thoracic radiologist.
      Computer generated summary sheets were used to present cases to each of six
      clinicians. Each case was presented three times: (1) with clinical data and chest
      radiograph only; (2) with the addition of the CT report; and (3) with all data
      including the result of the FNB. Clinicians were asked to specify their
      management on each occasion and to estimate the probability of the lesion being
      malignant. Reproducibility was assessed by re-evaluating 24 cases 1 month later.
      RESULTS: 33 (29%) nodules were benign, 35 (31%) nodules (malignant) were resected
      with negative node sampling, and 46 (40%) had a non-curative outcome
      (radiotherapy, incomplete resection, refused therapy). Intra-clinician decision
      making was consistent for all three levels of clinical data (median kappa values
      0.79-0.89). Agreement between clinicians on the need for surgery was lowest with
      chest radiography alone (kappa=0.33), rose with CT information (kappa=0.44), and
      increased further with the addition of the FNB data (kappa=0.57). The proportion
      of successful decisions on surgical intervention (against the known outcome)
      increased with the addition of CT reports and further with FNB reports (p=0.006,
      Friedman's test). The major benefit of the information added by CT and FNB
      reports was a reduction in unnecessary surgery, especially when the clinical
      perception of pre-test probability of malignancy was intermediate (31-70%). FNB
      data contributed most to the benefit (p<0.001). The addition of CT and FNB was
      cost efficient and can be applied specifically to patients with a low or
      intermediate probability of malignancy. CONCLUSION: Both CT and FNB make cost
      effective contributions to the clinical management of SPN < or = 3 cm in diameter
      by reducing unnecessary operations and increasing agreement between physicians on
      the need for surgery.

PMID- 12200529
TI  - The pulmonary physician in critical care - part 9: non-ventilatory strategies in
      ARDS.
AB  - Pharmacological approaches to the treatment of ARDS are reviewed. Future
      treatments should be targeted at elements of the pathological process that
      produce specific clinical problems.

PMID- 12200530
TI  - Chronic obstructive pulmonary disease - part 2: pathology and biochemistry of
      emphysema.
AB  - The pathology and pathogenesis of emphysema are reviewed, with particular
      reference to the proteinase-antiproteinase hypothesis.

PMID- 12200531
TI  - Chronic respiratory failure: an unusual cause and treatment.
AB  - Hypoventilation secondary to brainstem stroke resulting in chronic respiratory
      failure is extremely uncommon. This case documents the treatment of chronic type
      II respiratory failure secondary to central hypoventilation with
      medroxyprogesterone, a new treatment option.

PMID- 12200532
TI  - Conventional RIA underestimates cortisol suppression in the presence of
      prednisolone.

PMID- 12200533
TI  - Inhaled corticosteroid dosage in asthma.

PMID- 12200534
TI  - GM-CSF therapy in pulmonary alveolar proteinosis.

PMID- 12200535
TI  - Enhancement of nucleoside phosphorylation activity in an acid phosphatase.
AB  - Escherichia blattae non-specific acid phosphatase (EB-NSAP) possesses a
      pyrophosphate-nucleoside phosphotransferase activity, which is C-5'-position
      selective. Current mutational and structural data were used to generate a mutant
      EB-NSAP for a potential industrial application as an effective and economical
      protein catalyst in synthesizing nucleotides from nucleosides. First, Gly74 and
      Ile153 were replaced by Asp and Thr, respectively, since the corresponding
      replacements in the homologous enzyme from Morganella morganii reduced the K(m)
      value for inosine and thus increased the productivity of 5'-IMP. We determined
      the crystal structure of G74D/I153T, which has a reduced K(m) value for inosine,
      as expected. The tertiary structure of G74D/I153T was virtually identical to that
      of the wild-type. In addition, neither of the introduced side chains of Asp74 and
      Thr153 is directly involved in the interaction with inosine in a hypothetical
      binding mode of inosine to EB-NSAP, although both residues are situated near a
      potential inosine-binding site. These findings suggested that a slight structural
      change caused by an amino acid replacement around the potential inosine-binding
      site could significantly reduce the K(m) value. Prompted by this hypothesis, we
      designed several mutations and introduced them to G74D/I153T, to decrease the
      K(m) value further. This strategy produced a S72F/G74D/I153T mutant with a 5.4
      fold lower K(m) value and a 2.7-fold higher V(max) value as compared to the wild
      type EB-NSAP.

PMID- 12200536
TI  - A critical assessment of the secondary structure alpha-helices and their termini
      in proteins.
AB  - Secondary structure prediction from amino acid sequence is a key component of
      protein structure prediction, with current accuracy at approximately 75%. We
      analysed two state-of-the-art secondary structure prediction methods, PHD and
      JPRED, comparing predictions with secondary structure assigned by the algorithms
      DSSP and STRIDE. The specific focus of our study was alpha-helix N-termini, as
      empirical free energy scales are available for residue preferences at N-terminal
      positions. Although these prediction methods perform well in general at
      predicting the alpha-helical locations and length distributions in proteins, they
      perform less well at predicting the correct helical termini. For example,
      although most predicted alpha-helices overlap a real alpha-helix (with relatively
      few completely missed or extra predicted helices), only one-third of JPRED and
      PHD predictions correctly identify the N-terminus. Analysis of neighbouring N
      terminal sequences to predicted helical N-termini shows that the correct N
      terminus is often within one or two residues. More importantly, the true N
      terminal motif is, on average, more favourable as judged by our experimentally
      measured free energies. This suggests a simple, but powerful, strategy to improve
      secondary structure prediction using empirically derived energies to adjust the
      predicted output to a more favourable N-terminal sequence.

PMID- 12200537
TI  - Identification of amino acids involved in protein structural uniqueness:
      implication for de novo protein design.
AB  - Structural uniqueness is characteristic of native proteins and is essential to
      express their biological functions. The major factors that bring about the
      uniqueness are specific interactions between hydrophobic residues and their
      unique packing in the protein core. To find the origin of the uniqueness in their
      amino acid sequences, we analyzed the distribution of the side chain rotational
      isomers (rotamers) of hydrophobic amino acids in protein tertiary structures and
      derived deltaS(contact), the conformational-entropy changes of side chains by
      residue-residue contacts in each secondary structure. The deltaS(contact) values
      indicate distinct tendencies of the residue pairs to restrict side chain
      conformation by inter-residue contacts. Of the hydrophobic residues in alpha
      helices, aliphatic residues (Leu, Val, Ile) strongly restrict the side chain
      conformations of each other. In beta-sheets, Met is most strongly restricted by
      contact with Ile, whereas Leu, Val and Ile are less affected by other residues in
      contact than those in alpha-helices. In designed and native protein variants,
      deltaS(contact) was found to correlate with the folding-unfolding cooperativity.
      Thus, it can be used as a specificity parameter for designing artificial proteins
      with a unique structure.

PMID- 12200538
TI  - Photo-control of peptide helix content by an azobenzene cross-linker: steric
      interactions with underlying residues are not critical.
AB  - Photo-control of protein conformation could prove useful for probing function in
      diverse biological systems. Recently, we reported photo-switching of helix
      content in a short peptide containing an azobenzene cross-linker between cysteine
      residues at positions i and i + 7 in the sequence. In the original sequence,
      underlying residues at positions i + 3 and i + 4 were made bulky as preliminary
      modelling suggested that this would enhance photo-control of helix content. To
      test this hypothesis, peptides with Val, Aib; Ile, Aib; and Ala, Ala at positions
      i + 3 and i + 4 were synthesized, cross-linked and characterized. Before cross
      linking, the peptides show distinct conformational behaviours: two with differing
      helix/coil mixtures whereas the other has a circular dichroism (CD) spectrum
      characteristic of beta-sheet and a tendency to aggregate. However, upon cross
      linking the peptides have very similar CD spectra: predominantly random coil in
      the dark but predominantly helical upon irradiation. These results refute the
      original hypothesis. Steric interactions between the linker and underlying
      residues do not appear to be critical for photo-switching behaviour. When the
      cross-linking bridge is lengthened by replacing the i, i + 7 cysteine residues
      with homocysteine, a lower degree of photo-control of helicity is observed.
      Furthermore, a non-cross-linking version of the azobenzene reagent is shown not
      to produce any photo-control of helicity. We conclude that the intramolecular
      cross-link is essential for photo-switching and that it should be applicable to a
      wide range of peptides and proteins.

PMID- 12200539
TI  - Metal-binding studies for a de novo designed calcium-binding protein.
AB  - To understand the key determinants in calcium-binding affinity, a calcium-binding
      site with pentagonal bipyramid geometry was designed into a non-calcium-binding
      protein, domain 1 of CD2. This metal-binding protein has five mutations with a
      net charge in the coordination sphere of -5 and is termed DEEEE. Fluorescence
      resonance energy transfer was used to determine the metal-binding affinity of
      DEEEE to the calcium analog terbium. The addition of protein concentration to
      Tb(III) solution results in a large enhancement of Tb(III) fluorescence due to
      energy transfer between terbium ions and aromatic residues in CD2-D1. In
      addition, both calcium and lanthanum compete with terbium for the same desired
      metal binding pocket. Our designed protein exhibits a stronger affinity for
      Tb(III), with a K(d) of 21 microM, than natural calcium-binding proteins with a
      similar Greek key scaffold.

PMID- 12200540
TI  - Subunit interface mutation disrupting an aromatic cluster in Plasmodium
      falciparum triosephosphate isomerase: effect on dimer stability.
AB  - A mutation at the dimer interface of Plasmodium falciparum triosephosphate
      isomerase (PfTIM) was created by mutating a tyrosine residue at position 74, at
      the subunit interface, to glycine. Tyr74 is a critical residue, forming a part of
      an aromatic cluster at the interface. The resultant mutant, Y74G, was found to
      have considerably reduced stability compared with the wild-type protein (TIMWT).
      The mutant was found to be much less stable to denaturing agents such as urea and
      guanidinium chloride. Fluorescence and circular dichroism studies revealed that
      the Y74G mutant and TIMWT have similar spectroscopic properties, suggestive of
      similar folded structures. Further, the Y74G mutant also exhibited a
      concentration-dependent loss of enzymatic activity over the range 0.1-10 microM.
      In contrast, the wild-type enzyme did not show a concentration dependence of
      activity in this range. Fluorescence quenching of intrinsic tryptophan emission
      was much more efficient in case of Y74G than TIMWT, suggestive of greater
      exposure of Trp11, which lies adjacent to the dimer interface. Analytical gel
      filtration studies revealed that in Y74G, monomeric and dimeric species are in
      dynamic equilibrium, with the former predominating at low protein concentration.
      Spectroscopic studies established that the monomeric form of the mutant is
      largely folded. Low concentrations of urea also drive the equilibrium towards the
      monomeric form. These studies suggest that the replacement of tyrosine with a
      small residue at the interface of triosephosphate isomerase weakens the subunit
      subunit interactions, giving rise to structured, but enzymatically inactive,
      monomers at low protein concentration.

PMID- 12200541
TI  - Improving the carboligase activity of benzoylformate decarboxylase from
      Pseudomonas putida by a combination of directed evolution and site-directed
      mutagenesis.
AB  - Benzoylformate decarboxylase (BFD) from Pseudomonas putida was subjected to
      directed molecular evolution to generate mutants with increased carboligase
      activity which is a side reaction of the enzyme. After a single round of random
      mutagenesis mutants were isolated which exhibited a 5-fold increased carboligase
      activity in aqueous buffer compared to the wild-type enzyme with a high
      enantiomeric excess of the product (S)-2-hydroxy-1-phenyl-propanone. From the
      same library, mutants with enhanced carboligase activity in water-miscible
      organic solvents have been isolated. The selected mutants have been characterized
      by sequencing, revealing that all mutants carry a mutation at Leu476, which is
      close to the active site but does not directly interact with the active center.
      BFD-L476Q has a 5-fold higher carboligase activity than the wild-type enzyme.
      L476 was subjected to saturation mutagenesis yielding eight different mutants
      with up to 5-fold increased carboligase activity. Surprisingly, all L476 mutants
      catalyze the formation of 2-hydroxy-1-phenyl-propanone with significantly higher
      enantioselectivity than the wild-type enzyme although enantioselectivity was not
      a selection parameter. Leu476 potentially plays the role of a gatekeeper of the
      active site of BFD, possibly by controlling the release of the product. The
      biocatalyst could be significantly improved for its side reaction, the C-C bond
      formation and for application under conditions that are not optimized in nature.

PMID- 12200542
TI  - Blocking the tunnel: engineering of Candida rugosa lipase mutants with short
      chain length specificity.
AB  - The molecular basis of chain length specificity of Candida rugosa lipase 1 was
      investigated by molecular modeling and site-directed mutagenesis. The synthetic
      lip1 gene and the lipase mutants were expressed in Pichia pastoris and assayed
      for their chain length specificity in single substrate assays using triglycerides
      as well as in a competitive substrate assay using a randomized oil. Mutation of
      amino acids at different locations inside the tunnel (P246F, L413F, L410W,
      L410F/S300E, L410F/S365L) resulted in mutants with a different chain length
      specificity. Mutants P246F and L413F have a strong preference for short chain
      lengths whereas substrates longer than C10 are hardly hydrolyzed. Increasing the
      bulkiness of the amino acid at position 410 led to mutants that show a strong
      discrimination of chain lengths longer than C14. The results obtained can be
      explained by a simple mechanical model: the activity for a fatty acid sharply
      decreases as it becomes long enough to reach the mutated site. In contrast, a
      mutation at the entrance of the tunnel (L304F) has a strong impact on C4 and C6
      substrates. This mutant is nevertheless capable of hydrolyzing chain lengths
      longer than C8.

PMID- 12200543
TI  - Exploring routes to stabilize a cationic pyridoxamine in an artificial
      transaminase: site-directed mutagenesis versus synthetic cofactors.
AB  - Two artificial transaminases were assembled by linking a pyridoxamine derivative
      within an engineered fatty acid binding protein. The goal of mimicking a native
      transamination site by stabilizing a cationic pyridoxamine ring system was
      approached using two different strategies. First, the scaffold of intestinal
      fatty acid binding protein (IFABP) was tailored by molecular modeling and site
      directed mutagenesis to position a carboxylate group close to the pyridine
      nitrogen of the cofactor. When these IFABP mutants (IFABP-V60C/L38K/E93E and 
      V60C/E51K/E93E) proved to be unstable, a second approach was explored. By N
      methylation of the pyridoxamine, a cationic cofactor was created and tethered to
      Cys60 of IFABP-V60C/L38K and -V60C/E51K; this latter strategy had the effect of
      permanently installing a positive charge on the cofactor. These chemogenetic
      assemblies catalyze the transamination between alpha-ketoglutarate and various
      amino acids with enantioselectivities of up to 96% ee. The pH profile of the
      initial rates is bell shaped and similar to native aminotransferases. The k(cat)
      values and the turnover numbers for these new constructs are the highest achieved
      to date in our system. This success was only made possible by the unique
      flexibility of the underlying enzyme design concept employed, which permits full
      control of both the protein scaffold and the catalytically active group.

PMID- 12200544
TI  - Cloning and sequence analysis of D-erythrulose reductase from chicken: its close
      structural relation to tetrameric carbonyl reductases.
AB  - Sequence analysis of a cDNA for D-erythrulose reductase from chicken liver showed
      that the deduced open reading frame encodes the protein with a molecular mass of
      26 kDa consisting of 246 amino acids. Although the reductase shares more than 60%
      identity in the amino acid sequence with the mouse tetrameric carbonyl reductase,
      these two enzymes have many biochemical differences; their substrate specificity,
      subcellular localization, organ distribution, etc. A three-dimensional structure
      of D-erythrulose reductase was predicted by comparative modeling based on the
      structure of the tetrameric carbonyl reductase (PDB entry = 1CYD). Most of the
      residues at the active site (within 4 A from the ligand) of the carbonyl
      reductase were also conserved in the D-erythrulose reductase. Nevertheless,
      Val190 and Leu146 in the active site of the tetrameric carbonyl reductase were
      substituted in the D-erythrulose reductase by Asn192 and His148, respectively.
      The substitutions in the active sites may be related to the difference in
      substrate specificity of the two enzymes. The phylogenic analysis of D
      erythrulose reductase and the other related proteins suggests that the protein
      described as a carbonyl reductase D-erythrulose reductase.

PMID- 12200545
TI  - Evolvability of random polypeptides through functional selection within a small
      library.
AB  - A directed evolution with phage-displayed random polypeptides of about 140 amino
      acid residues was followed until the sixth generation under a selection based on
      affinity to a transition state analog for an esterase reaction. The experimental
      design deliberately limits the observation to only 10 clones per generation. The
      first generation consists of three soluble random polypeptides and seven
      arbitrarily chosen clones from a previously constructed library. The clone
      showing the highest affinity in a generation was selected and subjected to random
      mutagenesis to generate variants for the next generation. Even within only 10
      arbitrarily chosen polypeptides in each of the generations, there are enough
      variants in accord to capacity of binding affinity. In addition, the binding
      capacity of the selected polypeptides showed a gradual continuous increase over
      the generation. Furthermore, the purified selected random polypeptides exhibited
      a gradual but significant increase in esterase activity. The ease of the
      functional development within a small sequence variety implies that enzyme
      evolution is prompted even within a small population of random polypeptides.

PMID- 12200546
TI  - Trojan particles: large porous carriers of nanoparticles for drug delivery.
AB  - We have combined the drug release and delivery potential of nanoparticle (NP)
      systems with the ease of flow, processing, and aerosolization potential of large
      porous particle (LPP) systems by spray drying solutions of polymeric and
      nonpolymeric NPs into extremely thin-walled macroscale structures. These hybrid
      LPPs exhibit much better flow and aerosolization properties than the NPs; yet,
      unlike the LPPs, which dissolve in physiological conditions to produce molecular
      constituents, the hybrid LPPs dissolve to produce NPs, with the drug release and
      delivery advantages associated with NP delivery systems. Formation of the large
      porous NP (LPNP) aggregates occurs via a spray-drying process that ensures the
      drying time of the sprayed droplet is sufficiently shorter than the
      characteristic time for redistribution of NPs by diffusion within the drying
      droplet, implying a local Peclet number much greater than unity. Additional
      control over LPNPs physical characteristics is achieved by adding other
      components to the spray-dried solutions, including sugars, lipids, polymers, and
      proteins. The ability to produce LPNPs appears to be largely independent of
      molecular component type as well as the size or chemical nature of the NPs.

PMID- 12200547
TI  - Complete genome sequence and comparative genomic analysis of an emerging human
      pathogen, serotype V Streptococcus agalactiae.
AB  - The 2,160,267 bp genome sequence of Streptococcus agalactiae, the leading cause
      of bacterial sepsis, pneumonia, and meningitis in neonates in the U.S. and
      Europe, is predicted to encode 2,175 genes. Genome comparisons among S.
      agalactiae, Streptococcus pneumoniae, Streptococcus pyogenes, and the other
      completely sequenced genomes identified genes specific to the streptococci and to
      S. agalactiae. These in silico analyses, combined with comparative genome
      hybridization experiments between the sequenced serotype V strain 2603 V/R and 19
      S. agalactiae strains from several serotypes using whole-genome microarrays,
      revealed the genetic heterogeneity among S. agalactiae strains, even of the same
      serotype, and provided insights into the evolution of virulence mechanisms.

PMID- 12200549
TI  - Ventilation with small tidal volumes.

PMID- 12200548
TI  - Identification of benzothiazoles as potential polyglutamine aggregation
      inhibitors of Huntington's disease by using an automated filter retardation
      assay.
AB  - Preventing the formation of insoluble polyglutamine containing protein aggregates
      in neurons may represent an attractive therapeutic strategy to ameliorate
      Huntington's disease (HD). Therefore, the ability to screen for small molecules
      that suppress the self-assembly of huntingtin would have potential clinical and
      significant research applications. We have developed an automated filter
      retardation assay for the rapid identification of chemical compounds that prevent
      HD exon 1 protein aggregation in vitro. Using this method, a total of 25
      benzothiazole derivatives that inhibit huntingtin fibrillogenesis in a dose
      dependent manner were discovered from a library of approximately 184,000 small
      molecules. The results obtained by the filter assay were confirmed by
      immunoblotting, electron microscopy, and mass spectrometry. Furthermore, cell
      culture studies revealed that 2-amino-4,7-dimethyl-benzothiazol-6-ol, a chemical
      compound similar to riluzole, significantly inhibits HD exon 1 aggregation in
      vivo. These findings may provide the basis for a new therapeutic approach to
      prevent the accumulation of insoluble protein aggregates in Huntington's disease
      and related glutamine repeat disorders.

PMID- 12200550
TI  - High-frequency oscillatory ventilation for the prevention of chronic lung disease
      of prematurity.
AB  - BACKGROUND: There remains uncertainty concerning the safety and efficacy of high
      frequency oscillatory ventilation as compared with those of conventional
      ventilation for the respiratory support of very preterm infants. We conducted a
      multicenter trial to determine whether early intervention with high-frequency
      oscillatory ventilation reduced mortality and the incidence of chronic lung
      disease among newborns with a gestational age of 28 weeks or less. METHODS: We
      randomly assigned preterm infants with a gestational age of 23 to 28 weeks to
      either conventional ventilation or high-frequency oscillatory ventilation within
      one hour after birth. Randomization was stratified according to center and
      gestational age (23 to 25 weeks or 26 to 28 weeks). RESULTS: A total of 400
      infants were assigned to high-frequency oscillatory ventilation, and 397 were
      assigned to conventional ventilation. The composite primary outcome (death or
      chronic lung disease, diagnosed at 36 weeks of postmenstrual age) occurred in 66
      percent of the infants assigned to receive high-frequency oscillatory ventilation
      and 68 percent of those in the conventional-ventilation group (relative risk in
      the group assigned to high-frequency oscillatory ventilation, 0.98; 95 percent
      confidence interval, 0.89 to 1.08). Similar proportions of infants died or had
      chronic lung disease in each gestational-age group. In both treatment groups
      treatment failure occurred in 10 percent of infants (relative risk in the group
      assigned to high-frequency oscillatory ventilation, 0.99; 95 percent confidence
      interval, 0.66 to 1.50). There were no significant differences between the groups
      in a range of other secondary outcome measures, including serious brain injury
      and air leak. CONCLUSIONS: The results obtained with high-frequency oscillatory
      ventilation and conventional ventilation do not differ significantly in the early
      treatment of respiratory disease in very preterm infants. Assessment of long-term
      effects will require additional follow-up.

PMID- 12200551
TI  - High-frequency oscillatory ventilation versus conventional mechanical ventilation
      for very-low-birth-weight infants.
AB  - BACKGROUND: The efficacy and safety of early high-frequency oscillatory
      ventilation as compared with conventional synchronized intermittent mandatory
      ventilation for the treatment of infants with very low birth weight have not been
      established. METHODS: We conducted a randomized, multicenter clinical trial to
      determine whether infants treated with early high-frequency oscillatory
      ventilation were more likely than infants treated with synchronized intermittent
      mandatory ventilation to be alive without requiring supplemental oxygen at 36
      weeks of postmenstrual age. Eligible infants weighed 601 to 1200 g at birth, were
      less than four hours of age, had received one dose of surfactant, and required
      ventilation with a mean airway pressure of at least 6 cm of water and a fraction
      of inspired oxygen of at least 0.25. Infants were stratified according to birth
      weight and exposure to prenatal corticosteroids and then randomly assigned to
      high-frequency oscillatory ventilation or synchronized intermittent mandatory
      ventilation. Ventilation was managed according to protocols designed to optimize
      lung inflation and blood gas values. RESULTS: Five hundred infants were enrolled
      in the study. Infants randomly assigned to high-frequency oscillatory ventilation
      were successfully extubated earlier than infants assigned to synchronized
      intermittent mandatory ventilation (P<0.001). Of infants assigned to high
      frequency oscillatory ventilation, 56 percent were alive without a need for
      supplemental oxygen at 36 weeks of postmenstrual age, as compared with 47 percent
      of those receiving synchronized intermittent mandatory ventilation (P=0.046).
      There was no difference between the groups in the risk of intracranial
      hemorrhage, cystic periventricular leukomalacia, or other complications.
      CONCLUSIONS: There was a small but significant benefit of high-frequency
      oscillatory ventilation in terms of the pulmonary outcome for very-low-birth
      weight infants without an increase in the occurrence of other complications of
      premature birth.

PMID- 12200552
TI  - Derivation of nephrogenic adenomas from renal tubular cells in kidney-transplant
      recipients.
AB  - BACKGROUND: Nephrogenic adenomas are benign, tumor-like lesions within the
      urothelial mucosa of the urinary tract that are not uncommon in renal-transplant
      recipients. We investigated the origin of nephrogenic adenomas in renal
      transplant recipients. METHODS: Tissue sections were analyzed by fluorescence in
      situ hybridization with the use of probes for the X and Y chromosomes, by
      immunohistochemical methods with the use of antibodies to renal tubular antigens,
      and by lectin histochemical methods. Forty-six nephrogenic adenomas from 29
      patients were analyzed. RESULTS: All nephrogenic adenomas in 14 female recipients
      of transplants from male donors and 10 male recipients of transplants from female
      donors showed the same sex-chromosome status as the donor kidney, but not the
      same sex-chromosome status as the recipient's surrounding bladder tissue. The
      nephrogenic adenomas from all 6 female recipients of transplants from female
      donors showed female chromosomes, and those from the 16 male recipients of
      transplants from male donors showed male chromosomes. The presence of aquaporin
      1, PAX2, and lectin-binding capacity for peanut agglutinin, Lotus tetragonolobus
      agglutinin, and Sophora japonica agglutinin in nephrogenic adenomas indicated an
      origin from renal tubular cells. CONCLUSIONS: Nephrogenic adenomas in renal
      transplant recipients are derived from tubular cells of the renal transplants and
      are not metaplastic proliferations of the recipient's bladder urothelium.

PMID- 12200553
TI  - Images in clinical medicine. Neonatal rash due to herpes gestationis.

PMID- 12200554
TI  - Insurance coverage and outcomes of in vitro fertilization.
AB  - BACKGROUND: Although most insurance companies in the United States do not cover
      in vitro fertilization, a few states mandate such coverage. METHODS: We used 1998
      data reported to the Centers for Disease Control and Prevention by 360 fertility
      clinics in the United States and 2000 U.S. Census data to determine utilization
      and outcomes of in vitro fertilization services according to the status of
      insurance coverage. RESULTS: Of the states in which in vitro fertilization
      services were available, 3 states (31 clinics) required complete insurance
      coverage, 5 states (27 clinics) required partial coverage, and 37 states plus
      Puerto Rico and the District of Columbia (302 clinics) required no coverage.
      Clinics in states that required complete coverage performed more in vitro
      fertilization cycles than clinics in states that required partial or no coverage
      (3.35 vs. 1.46 and 1.21 transfers per 1000 women of reproductive age,
      respectively; P<0.001) and more transfers of frozen embryos (0.43 vs. 0.30 and
      0.20 per 1000 women of reproductive age, respectively; P<0.001). The percentage
      of cycles that resulted in live births was higher in states that did not require
      any coverage than in states that required partial or complete coverage (25.7
      percent vs. 22.2 percent and 22.7 percent, respectively; P<0.001), but the
      percentage of pregnancies with three or more fetuses was also higher (11.2
      percent vs. 8.9 percent and 9.7 percent, respectively; P=0.007). The number of
      fresh embryos transferred per cycle was lower in states that required complete
      coverage than in states that required partial or no coverage (P=0.001 and
      P<0.001, respectively). CONCLUSIONS: State-mandated insurance coverage for in
      vitro fertilization services is associated with increased utilization of these
      services but with decreases in the number of embryos transferred per cycle, the
      percentage of cycles resulting in pregnancy, and the percentage of pregnancies
      with three or more fetuses.

PMID- 12200555
TI  - Clinical practice. Adolescent depression.

PMID- 12200556
TI  - Case records of the Massachusetts General Hospital. Weekly clinicopathological
      exercises. Case 27-2002. A 5(1/2)-year-old boy with seizures and progressive
      deterioration of cognitive and motor function.

PMID- 12200557
TI  - High-frequency oscillatory ventilation to prevent bronchopulmonary dysplasia--are
      we there yet?

PMID- 12200558
TI  - Nephrogenic adenomas as renal tubular outposts.

PMID- 12200559
TI  - Should insurance coverage for in vitro fertilization be mandated?

PMID- 12200560
TI  - Responses to smallpox vaccine.

PMID- 12200561
TI  - Diagnosis of smallpox.

PMID- 12200562
TI  - Smallpox and smallpox vaccination.

PMID- 12200563
TI  - Brachytherapy and saphenous-vein grafts.

PMID- 12200564
TI  - Clinical investigation in the 18th century.

PMID- 12200565
TI  - Volume and outcome.

PMID- 12200566
TI  - Combined blood substitute and erythropoietin therapy in a severely injured
      Jehovah's Witness.

PMID- 12200567
TI  - Bronchial cast.

PMID- 12200568
TI  - Acute babesiosis caused by Babesia divergens in a resident of Kentucky.

PMID- 12200569
TI  - Large-area phase-contrast X-ray imaging using a two-crystal X-ray interferometer.
AB  - Large-area (25 x 20 mm) phase-contrast X-ray imaging was attained by using a skew
      symmetric two-crystal X-ray interferometer. The sub-nrad angular control required
      to operate the X-ray interferometer was achieved with a sleeve bearing and a
      feedback-positioning system. As a demonstration, measurements of a phase map of a
      rat's liver and a phase-contrast tomographic three-dimensional image of a piece
      of a rabbit's liver were performed at the Photon Factory using 0.07 nm
      synchrotron radiation X-rays.

PMID- 12200570
TI  - X-ray diffraction topography using a diffractometer with a bendable monochromator
      at a synchrotron radiation source.
AB  - The different properties of laboratory- and synchrotron-based double-crystal
      setups for X-ray topographic applications are discussed as a basis for the
      realization of a versatile instrument allowing the investigation of all kinds of
      crystals with high strain sensitivity and without any reduction in image size. It
      appears that the use of a bendable highly perfect monochromator (silicon)
      achieves this goal, through the local adaptation of Bragg angles, to compensate
      either dispersion or a bending of the sample.

PMID- 12200571
TI  - Diffuse scattering from liquid solutions with white-beam undulator radiation for
      photoexcitation studies.
AB  - Scattering from molecules in solution is a natural way to study fast reactions in
      solution with X-ray probes. With the availability of reliable femtosecond laser
      systems and pulsed synchrotron sources with high brilliance, it has become
      possible to study picosecond time-resolved photoexcitation in condensed matter.
      Owing to the low scattering cross section and the high background from the non
      excited solvent, high flux and long exposure times are required to obtain
      information about isolated molecules in the conventional monochromatic scattering
      scheme. It is proposed that the full spectrum of a single-line undulator be used
      to obtain the diffuse scattering distribution. The bandwidth of 2-5% of the first
      harmonic, which is easily achievable in current insertion devices, is sufficient
      to allow the derivation of molecular form factors even in diluted systems. The
      relaxed bandwidth augments the usable flux drastically.

PMID- 12200572
TI  - Time dependence of the polarization of short X-ray pulses after crystal
      reflection.
AB  - The short X-ray pulses coming out of a SASE FEL (self-amplified stimulated
      emission free-electron laser) have stimulated a closer inspection of the response
      of a crystal reflection to them. As the reflectivity of a crystal reflection
      depends on the polarization of the incident radiation, the time response does so
      as well. The response to a delta-pulse incident either under 45 degrees linearly
      polarized with respect to the reflection plane of a monochromator crystal or
      circularly polarized is investigated in more detail. In contrast to the purely
      linear polarization perpendicular and parallel to the reflection plane, these
      mixed states show a very pronounced time dependence. In addition, a simulated
      SASE FEL bunch is investigated as an incident intensity distribution.

PMID- 12200573
TI  - Interaction of atomic systems with X-ray free-electron lasers.
AB  - The planned construction of an X-ray free-electron laser (XFEL) will provide new
      opportunities for research in various areas of physics, chemistry and biology.
      The proposed design of the XFELs at DESY (Deutsches Elektronen-Synchrotron) and
      SLAC (Stanford Linear Accelerator Center) is built on the concept of a fourth
      generation synchrotron source and will provide an intense pulse (I(0)
      approximately 10(16) W cm(-2), tau(gamma) approximately 100 fs) for photon
      wavelengths down to 1 A. Some guidelines for applications of these sources
      pertaining to atomic physics are presented here. Issues such as the onset of
      strong photon-field effects, multiple ionization and hollow-atom formation are
      analyzed. Attention is especially given to studying the interaction with rare-gas
      atoms, for which some numerical estimates are provided.

PMID- 12200574
TI  - First steps towards time-resolved BioXAS at room temperature: state transitions
      of the manganese complex of oxygenic photosynthesis.
AB  - Structural changes and redox transitions at the metal atoms of the active site
      are essential for the understanding of the catalytic mechanisms of biological
      metalloenzymes. First steps towards studying these processes by time-resolved X
      ray absorption spectroscopy on protein samples (BioXAS) are reported. Photosystem
      II (PSII) catalyses the light-driven oxidation of bound water molecules at a
      tetranuclear manganese complex yielding the molecular oxygen of the atmosphere.
      In this work, first time-resolved XAS results under quasi-physiological
      conditions (at room temperature, non-crystalline samples) on PSII are presented.
      Perspectives of time-resolved BioXAS are discussed.

PMID- 12200575
TI  - X-ray diffractometer designed for industrial applications at SPring-8 BL24XU.
AB  - An X-ray diffractometer for industrial applications has been designed, installed
      at SPring-8 BL24XU and tested by measuring a standard Al(2)O(3) powder sample.
      The measurement results prove the high precision of the diffractometer. The
      diffractometer was also tested by conducting grazing-incidence X-ray diffraction
      measurements of ion-implanted chromium-coated steel. The validity of a new method
      for X-ray stress measurements of polished stainless steel is also proposed and
      confirmed. The results prove the suitability of this diffractometer for
      industrial applications.

PMID- 12200576
TI  - Nearly diffraction-limited line focusing of a hard-X-ray beam with an
      elliptically figured mirror.
AB  - An elliptical mirror for X-ray microfocusing was manufactured using the new
      fabrication methods of elastic emission machining and plasma chemical
      vaporization machining. Surface profiles measured using stitching interferometry
      showed a maximum deviation around the ideal figure of 7 nm peak-to-valley. The
      mirror showed nearly diffraction-limited focusing performance, with a 200 nm line
      width at the focus. Wave-optical calculations, taking the measured surface
      profile into consideration, reproduced well the measured focusing properties both
      at and around the beam waist.

PMID- 12200577
TI  - Cryogenically cooled bent double-Laue monochromator for high-energy undulator X
      rays (50-200 keV).
AB  - A liquid-nitrogen-cooled monochromator for high-energy X-rays consisting of two
      bent Si(111) Laue crystals adjusted to sequential Rowland conditions has been in
      operation for over two years at the SRI-CAT sector 1 undulator beamline of the
      Advanced Photon Source (APS). It delivers over ten times more flux than a flat
      crystal monochromator does at high energies, without any increase in energy width
      (DeltaE/E approximately 10(-3)). Cryogenic cooling permits optimal flux, avoiding
      a sacrifice from the often employed alternative technique of filtration - a
      technique less effective at sources like the 7 GeV APS, where considerable heat
      loads can be deposited by high-energy photons, especially at closed undulator
      gaps. The fixed-offset geometry provides a fully tunable in-line monochromatic
      beam. In addition to presenting the optics performance, unique crystal design and
      stable bending mechanism for a cryogenically cooled crystal under high heat load,
      the bending radii adjustment procedures are described.

PMID- 12200578
TI  - New pressure flow cell to monitor BaSO4 precipitation using synchrotron in situ
      angle-dispersive X-ray diffraction.
AB  - A flow cell has been commissioned to monitor in situ precipitation reactions
      under non-ambient conditions. The majority of high-pressure systems use anvils
      and presses to obtain high pressures around a small reaction area; however, this
      prototype is unique in that solutions may be examined as they flow through the
      cell under pressure. The cell is made of single-crystal silicon, which is capable
      of withstanding the high pressures created by liquid flow within the cell. With
      the capability of reaching pressures of up to 4 x 10(7) Pa, the cell is ideal for
      work on geological and oilfield systems. Here it is used to examine the formation
      of barium sulfate scale in situ under non-ambient conditions using angle
      dispersive XRD on beamline X17b1 at the NSLS.

PMID- 12200580
TI  - OLAW clarifies PHS policy regarding use of carbon dioxide for euthanasia of small
      laboratory animals.

PMID- 12200581
TI  - When the AV and PI don't see eye to eye.

PMID- 12200582
TI  - Mandibular mass in a young Swiss-Webster mouse.

PMID- 12200583
TI  - Disaster Recovery: "who ya gonna call?".

PMID- 12200584
TI  - The year of the flood: Tropical Storm Allison's impact on Texas Medical Center.

PMID- 12200585
TI  - Protecting your institution from cybersabotage.

PMID- 12200586
TI  - Vasectomy as a birth control modality for captive chimpanzees.

PMID- 12200587
TI  - Animal use on the decline in medical schools.

PMID- 12200588
TI  - New legislation will protect animal facilities.

PMID- 12200589
TI  - Protocol approval for outside training programs: here or there?

PMID- 12200590
TI  - Heterotopic bone in the eyes of a guinea pig: osseous choristoma of the ciliary
      body.

PMID- 12200591
TI  - The role of ICCVAM in evaluating new and alternative test methods.

PMID- 12200592
TI  - Murine local lymph node assay: an alternative test method for skin
      hypersensitivity testing.

PMID- 12200593
TI  - Alternative methods for acute oral toxicity testing: practical guidance for
      implementation.

PMID- 12200594
TI  - Postoperative analgesia in the laboratory mouse, Mus musculus.

PMID- 12200595
TI  - A gavage dosing apparatus with flexible catheter provides a less stressful gavage
      technique in the rat.

PMID- 12200596
TI  - Impact of microsatellite testing and mismatch repair protein expression on the
      clinical interpretation of genetic testing in hereditary non-polyposis colorectal
      cancer.
AB  - PURPOSE: Identification of germline mutations in mismatch repair genes is
      increasingly being used to guide clinical practice in hereditary non-polyposis
      colon cancer. The aim of this study was to retrospectively assess the clinical
      utility of immunostaining and microsatellite instability testing in a group of
      individuals in whom germline testing of hMSH2 and hMLH1 had already been
      performed. METHODS: Individuals were identified from the records of family cancer
      clinics. A total of thirty-eight tumour blocks were retrieved from 28 kindreds.
      DNA was extracted and PCR amplification of six microsatellite markers was
      performed. Immunostaining was used to examine the expression of hMSH2 and hMLH1
      protein. RESULTS: Of the 32 assessable tumours, 24 (75%) showed microsatellite
      instability. Most of the MSI-H cancers (92%) failed to express either hMLH1 or
      hMSH2. Deleterious germline mutations were identified in the proband in 12 of 28
      families. Missense mutations were identified in 11 cases and no mutations in six
      probands. CONCLUSIONS: The use of germline genetic testing is indicated for a
      highly selected group of individuals. MSI testing and immunostaining are
      extremely useful tools which significantly improve the clinical interpretation of
      germline results. Ambiguity regarding the significance of missense mutations in
      hereditary bowel cancer suggests that these findings should be interpreted with
      caution.

PMID- 12200597
TI  - Overexpression of cyclin B1 in gastric cancer and its clinicopathological
      significance: an immunohistological study.
AB  - PURPOSE: Cyclin B1 is a key regulator of progression through the G2/M transition
      during the cell cycle. Although cyclin B1 proteins are overexpressed in various
      types of human cancers, the relationship between cyclin B1 status in gastric
      cancer and its clinical significance remains unknown. METHODS: We examined cyclin
      B1 expression by immunohistological means in 61 patients with gastric cancer in
      terms of histological type, tumor invasion, and metastatic behavior. Specimens
      were considered positive when the cytoplasm of over 10% of the cancer cell
      population was stained. RESULTS: Cyclin B1 was overexpressed in 32 (53%) of 61
      patients with gastric cancer. Tumors that expressed cyclin B1 were predominant in
      older patients, in well- and moderately differentiated adenocarcinomas and in
      expanding-growth type tumors. Conversely, expression of cyclin B1 was lower in
      poorly differentiated adenocarcinomas, and in those of the infiltrative growth
      type. Moreover, the disease was more advanced (stages III and IV) and widespread
      nodal involvement was more frequent when cyclin B1 expression was low. Logistic
      regression analyses showed that histological type is a significant factor related
      to cyclin B1 protein expression. CONCLUSIONS: These findings suggested that
      cyclin B1 protein overexpression is closely associated with less aggressive tumor
      behavior. Therefore, G2/M cyclin alternatives and the possible role of cyclins in
      cancer development warrants further attention.

PMID- 12200598
TI  - Long-term survival in patients with brain metastases.
AB  - PURPOSE: The aims of this study are: (a) to determine long-term survival in
      patients with brain metastases who underwent whole brain radiation therapy; (b)
      to evaluate whether long-term survival can be predicted by the Radiation Therapy
      Oncology Group (RTOG) recursive partitioning analysis (RPA); and (c) to review
      the literature on long-term survival. MATERIAL AND METHODS: The records of 916
      patients with brain metastases who underwent whole brain radiation therapy at our
      hospital from 1985 to 2000 were analyzed retrospectively. RESULTS: By July 2001,
      891 patients had died. Median survival of the whole group was 3.4 months. Overall
      survival was 5.6% at 2 years (at risk: n=48), 2.9% at 3 years ( n=25), 1.8% at 5
      years ( n=12), and <1% at 10 years ( n=1). Survival for 2 years or more was
      observed in RTOG RPA class 1, but also in class 2 patients. Within both classes,
      survival was significantly better for patients with a single brain metastasis
      compared with those patients having multiple metastases. A survey of the
      literature revealed that in rare instances survival of 10 years or more was seen
      in patients with brain metastases. The majority of these patients had a single
      brain metastasis treated by radical resection and whole brain radiation therapy.
      CONCLUSION: Even in patients with favorable characteristics, survival for 2 years
      or more after the diagnosis of brain metastases is considerably low. Aggressive
      therapy in RPA class 1 and class 2 patients with a single brain metastasis
      occasionally permits long-term survival.

PMID- 12200599
TI  - Expression of the 27-kDa heat shock protein (HSP27) in gastric carcinomas and
      adjacent normal, metaplastic, and dysplastic gastric mucosa, and its prognostic
      significance.
AB  - PURPOSE: The investigation of heat shock protein 27 (HSP27) expression in gastric
      cancer and adjacent normal, metaplastic, and dysplastic gastric mucosa and its
      correlation with clinicopathological parameters and survival of patients.
      METHODS: Immunohistochemical methodology was performed on formalin-fixed paraffin
      embedded sections by using a monoclonal anti-HSP27 antibody. HSP27 expression was
      screened and compared in 86 cases of gastric carcinoma and adjacent normal,
      metaplastic, and dysplastic gastric mucosa. RESULTS: In the normal mucosa, HSP27
      was detected in 68 out of 86 cases (79%) and was more intense in the surface and
      upper two-thirds of gastric foveolae. In dysplastic gastric mucosa, HSP27
      immunoreactivity was usually higher than that of the adjacent normal epithelium
      and was parallel to the severity of dysplasia. HSP27 expression was found in 54
      out of 86 (62.7%) gastric carcinomas and was significantly related to more than
      six metastatic lymph nodes ( P =0.03). HSP27 expression was also higher in tumors
      of advanced stage and in those of female patients. HSP27 expression was
      associated with shorter overall survival in univariate analysis ( P =0.04), but
      this relationship was not retained in multivariate analysis. CONCLUSIONS: Our
      findings indicate that: i) HSP27 is commonly expressed in normal gastric
      epithelium where it seems to exert a protective role; and ii) HSP27 is involved
      in gastric carcinogenesis and its expression appears to be associated with
      parameters of unfavorable prognosis and shorter overall survival.

PMID- 12200600
TI  - Augmented antitumour effects of combination therapy with TNP-470 and
      chemoimmunotherapy in mice.
AB  - PURPOSE: To investigate antitumour efficacy of the combination of the
      antiangiogenic agent TNP-470 combined with chemoimmunotherapy in different tumour
      models in mice MATERIALS: B6D2F1 mice and BALB/c mice were inoculated in the
      footpad of the right hind limb with B16F10 melanoma cells or colon adenocarcinoma
      cells C-26, respectively. Subsequently, they received therapy consisting of TNP
      470 and/or IL-12 and tumour growth was observed. In the melanoma model this
      therapy regimen was combined with cisplatin in a subtherapeutic dose. The
      antiangiogenic action of the tested agents was evaluated using tumour-induced
      angiogenesis assay in vivo. In order to analyse interactions between TNP-470 (or
      cisplatin) and IFN-gamma on tumour cells in vitro, the following methods were
      used: MTT assay, Western blot analysis, and flow cytometry analysis. RESULTS:
      Administration of the combined therapy with TNP-470 and IL-12 resulted in
      augmented antitumour activity in colon-26 and B16F10 melanoma models. Addition of
      cisplatin further enhanced efficacy of this combined therapy in the melanoma
      model. We showed that antitumour activity of this combined therapy is mediated by
      multiple mechanisms: not only is enhancement of the antiangiogenic activity
      mediated by TNP-470 and IL-12 but also by the synergistic cytostatic/cytotoxic
      action of IL-12-induced IFN-gamma and TNP-470 or cisplatin on tumour cells. The
      experiments revealed that TNP-470 together with IFN-gamma leads to the increased
      expression of p21 protein in cancer cells, which in turn may contribute to their
      cytostatic/cytotoxic action in vitro. CONCLUSION: Our experiments show a
      successful TNP-470-based combination therapy and suggest that the enhancement of
      the antitumour activity could be explained by a concomitant effect on both
      endothelial and tumour cell compartments.

PMID- 12200601
TI  - Soluble HLA class I molecules in malignant pleural and peritoneal effusions and
      its possible role on NK and LAK cytotoxicity.
AB  - PURPOSE: To examine the amount of sHLA-I in malignant pleural and peritoneal
      effusions and its possible role in natural immune defense. METHODS: Three groups
      of patients (75 patients with malignancy, 21 with infection, and 27 with other
      diseases) were studied for sHLA-I value using an ELISA method. Cytolytic activity
      of freshly isolated pleural and peritoneal effusion-associated lymphoid (EAL)
      cells from 14 of cases with malignancy were examined and compared to that of ten
      non-cancerous patients. EAL cells were co-cultured with the autologous cell-free
      effusions immediately after collection and 3 days after incubation with IL-2.
      RESULTS: The mean value of sHLA-I in effusions was 1.01+/-1.36 micro g/ml, 0.97+/
      1.20 micro g/ml, and 0.49+/-0.45 micro g/ml, respectively. Despite higher mean
      sHLA-I levels in malignant and infected patients, no significant difference
      between these groups was observed ( P >0.05). Generally, the amount of sHLA-I in
      peritoneal effusions was higher than that for pleural effusions, but the
      difference was not significant. There were also no statistical differences in the
      sHLA-I levels between sub-groups of patients with malignancy. EAL cells' killing
      activity in malignant and infected effusions was 68.15+/-11.73 and 78.28+/-14.41,
      respectively ( P=0.08). No correlation between sHLA-I level and NK activity of
      EAL cells from the patients was found. Almost all malignant cases after exposure
      to cell-free effusions displayed an increase in NK activity (from 68.66+/-11.13
      to 74.2+/-12.39, P=0.042) and a decrease in LAK activity (74.5+/-18.30 vs 67.72+/
      16.46, P=0.040). Whereas, the same experiment performed for non-malignant
      effusions showed a decrease in both NK activity and LAK activity. Changes in NK
      and LAK activity were not correlated with the amount of sHLA-I in the effusions.
      CONCLUSION: The presence of sHLA-I, particularly in malignant effusions, suggests
      a role for these molecules in tumor immunity in the peritoneal or plural
      environment; however, at least with these group of patients, sHLA-I appears not
      to be a unique determining factor on EAL cells' killing activity.

PMID- 12200603
TI  - p53 Germline mutation in a patient with Li-Fraumeni Syndrome and three
      metachronous malignancies.
AB  - PURPOSE: Germline mutations of the p53 coding region are present in approximately
      50-70% of patients with Li-Fraumeni Syndrome (LFS), a rare hereditary disorder of
      familial and intraindividual clustering of different malignancies such as sarcoma
      (index tumor), breast cancer, brain tumors, leukemias, and adrenocortical
      carcinomas, the latter usually in young children. Both onset and spectrum of
      malignancies in individuals with LFS are thus heterogenous and may, less
      frequently, also include other epithelial and mesenchymal tumors. A 32-year-old
      female presented for genetic counseling with a history of leiomyosarcoma at age
      22, malignant melanoma (a rare component of LFS) at age 26, and breast cancer at
      age 30. All three tumors had been treated surgically. Astrocytoma and breast
      cancer, respectively, had been diagnosed in her brother and mother before age 30.
      Other malignancies diagnosed early in life in relatives of the mother were:
      prostate cancer, stomach cancer, and carcinoma of the larynx. METHODS: Upon
      written informed consent, DNA was extracted from peripheral blood mononuclear
      cells of the proband, and p53 exons 4-8 analyzed for mutations by SSCP and DNA
      sequencing. RESULTS: A G:C to A:T mutation at codon 175 of p53 resulting in an
      arginine --> histidine substitution was detected, confirming the clinical
      diagnosis of LFS. CONCLUSIONS: The patient and her family are being followed
      further, but testing of her children for the presence of this mutation is
      currently being withheld. The difficulties in the management and treatment of
      patients with this clinically heterogenous disorder are discussed.

PMID- 12200602
TI  - Ondansetron but not granisetron affect cell volume regulation and potassium ion
      transport of glioma cells treated with estramustine phosphate.
AB  - PURPOSE: Highly 5-HT(3)-receptor-specific antiemetic agents may have different
      effects on ion transport of tumour cells during treatment with cytotoxic drugs.
      Cell volume regulation, which is dependent on potassium ion (K(+)) flux, is
      involved the control of cell growth, proliferation, and apoptosis. K(+)-flux
      response mechanisms to the antiemetics ondansetron and granisetron were therefore
      correlated to malignant glioma cell (Mg251) volume response to estramustine
      phosphate (EMP) in vitro. METHODS: We quantified the influx and efflux of
      potassium ions (using the K(+) analogue (86)Rb(+)) as well as cell volume changes
      (with image analysis) of glioma cells incubated with the 5-HT(3)-receptor
      antagonists ondansetron and granisetron (0.1 micro mol/l) combined with 40 mg/l
      EMP. RESULTS: The EMP-induced cell volume increase was fully inhibited by
      ondansetron but not affected by granisetron. Ondansetron retained high cellular
      K(+)-efflux and reduced Na(+), K(+), 2Cl(-)-cotransport activity, whereas
      granisetron (0.1 micro mol/l) reduced K(+)-efflux and retained an augmented
      Na(+), K(+), 2Cl(-)-cotransport activity in the presence of 40 mg/l EMP.
      CONCLUSIONS: Ondansetron affects K(+) transport with ensuing effects on cell
      volume of tumour cells treated with EMP, whereas granisetron does not. Since
      ondansetron and other 5-HT(3)-receptor antagonists are used routinely to prevent
      nausea during anticancer treatment, an increased awareness of possible
      interactions with the antitumour efficacy of anticancer drugs seems warranted.

PMID- 12200604
TI  - Antibody responsiveness to the enteropathogenic Escherichia coli bundle-forming
      pilus subunit A in lactating mothers and asymptomatic children.
AB  - The objective of this study was to examine the antibody responsiveness to the
      bundle-forming pilus subunit A of enteropathogenic Escherichia coli in human
      colostrum (n = 36) and serum (n = 90) of paediatric ambulatory patients, 3-24
      months of age. Affinity purified recombinant bundle-forming pilus subunit A was
      used in immunoblot analysis to detect antigen-specific serum immunoglobulins G
      and A, and colostrum immunoglobulin A. Circulating immunoglobulin G antibody
      activity to the bundle-forming pilus subunit A was readily detected in all
      children. The frequency of immunoglobulin A antibody activity to the bundle
      forming pilus subunit A in serum was 83.3%. Immunoglobulin A antibody activity to
      the bundle-forming pilus subunit A was detected in 75% of colostrum samples. The
      high frequency of immunoglobulin A antibody activity to the bundle-forming pilus
      subunit A observed in serum reveals a predominance of typical enteropathogenic
      Escherichia coli priming/infection in the study population. CONCLUSION: these
      findings demonstrate that the bundle-forming pilus subunit A is immunogenic, for
      both immunoglobulins G and A, in both pregnant/lactating women and asymptomatic
      children.

PMID- 12200605
TI  - Acrodermatitis enteropathica-like eruption as the presenting sign of cystic
      fibrosis--case report and review of the literature.
AB  - In most patients with cystic fibrosis (CF), pulmonary symptoms are the first sign
      of presentation. Another predominant feature is maldigestion, frequently starting
      in early childhood. Pancreatic exocrine dysfunction causes maldigestion,
      characterised by failure to thrive, diarrhoea, hypoproteinaemia, oedema and
      anaemia. Dermatitis may be the initial manifestation in just a few patients with
      CF. We report on a patient presenting with refractory dermatitis resembling
      acrodermatitis enteropathica as the first sign of CF at the age of 4 months, but
      without pulmonary symptoms. Laboratory findings demonstrated anaemia,
      hypoproteinaemia and zinc deficiency. Peroral zinc substitution resulted in
      resolution of the dermatitis within a few days. A further work-up revealed a
      positive sweat test and homozygosity for the deltaF-580 mutation. CONCLUSION: in
      rare cases, acrodermatitis enteropathica-like dermatitis is the first symptom of
      cystic fibrosis.

PMID- 12200606
TI  - A new case of autosomal recessive agammaglobulinaemia with impaired pre-B cell
      differentiation due to a large deletion of the IGH locus.
AB  - Males with X-linked agammaglobulinaemia (XLA) due to mutations in the Bruton
      tyrosine kinase gene constitute the major group of congenital
      hypogammaglobulinaemia with absence of peripheral B cells. In these cases,
      blockages between the pro-B and pre-B cell stage in the bone marrow are found.
      The remaining male and female cases clinically similar to XLA represent a
      genotypically heterogeneous group of diseases. In these patients, various
      autosomal recessive disorders have been identified such as mutations affecting
      IGHM, CD79A, IGLL1 genes involved in the composition of the pre-B cell receptor
      (pre-BCR) or the BLNK gene implicated in pre-BCR signal transduction. In this
      paper, we report on a young female patient characterised by a severe non-XLA
      agammaglobulinaemia that represents a new case of Igmu defect. We show that the B
      cell blockage at the pro-B to pre-B cell transition is due to a large homologous
      deletion in the IGH locus encompassing the IGHM gene leading to the inability to
      form a functional pre-BCR. The deletion extends from the beginning of the
      diversity (D) region to the IGHG2 gene, with all JH segments and IGHM, IGHD,
      IGHG3 and IGHG1 genes missing. CONCLUSION: alteration in Igmu expression seems to
      be relatively frequent and could account for most of the reported cases of
      autosomal recessive agammaglobulinaemia.

PMID- 12200607
TI  - Functional residual capacity and compliance of the respiratory system after
      surfactant treatment in premature infants with severe respiratory distress
      syndrome.
AB  - To understand the mechanisms behind improved oxygenation after intratracheal
      surfactant instillation, the immediate and late effects on lung volume and
      compliance of the respiratory system (CRS) were analysed. Infants received
      modified porcine surfactant (Curosurf) or modified bovine surfactant (Alveofact).
      Measurements of functional residual capacity (FRC) and CRS were successfully
      performed in 90 ventilated preterm infants (birth weight 1264 +/- 435 g;
      gestational age 28.2 +/- 2.5 weeks) with severe respiratory distress syndrome.
      FRC and CRS were measured during mechanical ventilation prior to and 1, 3, 6, 24,
      48, 72, 96, 120 and 168 h after surfactant replacement. Oxygenation rapidly
      improved. FRC increased significantly from 7.64 +/- 1.58 ml/kg to 15.35 +/- 3.27
      ml/kg (P < 0.01) at 1 h after surfactant instillation. CRS remained virtually
      unchanged during the first hours after surfactant replacement and a concomitant
      decrease in specific compliance was seen. CONCLUSION: the changes in lung
      function following surfactant treatment can only be explained by initial
      stabilisation of already aerated alveoli followed by recruitment of new gas
      exchange units as mechanisms involved in mediating the effect of surfactant on
      gas exchange. However, since no significant correlation between changes in
      functional residual capacity and improvement in arterial-to-alveolar oxygen
      tension ratio was seen, other effects of surfactant must be considered. These
      include local and/or systemic changes in haemodynamics.

PMID- 12200608
TI  - Severe Coxsackie virus B infection in preterm newborns treated with pleconaril.
AB  - Four preterm newborn infants with severe multisystem Coxsackie virus B infection
      were treated with an oral suspension of pleconaril (5 mg/kg per day). The
      patients had myocarditis, fulminant hepatitis, meningoencephalitis and
      disseminated intravascular coagulopathy. All four infants recovered, and no
      adverse effects of the treatment were noted. CONCLUSION: pleconaril needs to be
      comprehensively evaluated in this population.

PMID- 12200609
TI  - Haemophagocytic lymphohistiocytosis following measles vaccination.
AB  - A 19-month-old girl developed haemophagocytic lymphohistiocytosis following a
      measles vaccination. She developed persistent high fever 1 week after
      vaccination, and then showed pancytopenia, liver dysfunction and
      hepatosplenomegaly with marked haemophagocytosis. Based on the clinical and
      laboratory findings, she was diagnosed as having haemophagocytic
      lymphohistiocytosis probably due to measles vaccination. She did not respond
      fully to first-line immunosuppressive therapy and required immunochemotherapy
      with cytotoxic drugs. CONCLUSION: To the best of our knowledge, this is the first
      detailed report of haemophagocytic lymphohistiocyosis associated with measles
      vaccination documented in the English literature. Haemophagocytic
      lymphohistiocyosis should be kept in mind as one of the rare adverse effects of
      vaccination.

PMID- 12200610
TI  - Toxic shock syndrome and streptococcal myositis: three case reports.
AB  - Group A streptococcal (GAS) infection is the most common cause of bacterial
      pharyngitis and has an important role in the pathogenesis of post-infective
      phenomena including rheumatic fever and glomerulonephritis. Mortality from GAS is
      uncommon, particularly in the paediatric population. Toxic shock syndrome
      reflects the most severe form of GAS-related disease and is often associated with
      fasciitis or myositis. CONCLUSION: We present three cases of toxic shock syndrome
      secondary to (GAS) myositis demonstrating the importance of early recognition and
      provision of intensive care management.

PMID- 12200611
TI  - Onset of cataract in early infancy associated with a 32G-->C transition in the
      iron responsive element of L-ferritin.
AB  - We describe the onset of cataract in early infancy in a family with hereditary
      hyperferritinaemia-cataract syndrome. The two probands presented with isolated
      hyperferritinaemia and had developed cataracts at the age of 18 months. Two
      members of their family with high ferritin levels (1270-1450 microg/l) had
      suffered from cataract since childhood. The mutation responsible was a 32G-->C
      change in the lateral bulge of the stem structure of the iron responsive element
      of the L-ferritin subunit gene. Mutations at this level cause particularly high
      ferritin levels, whereas the age of cataract onset and its severity are
      controversial subjects. In our family, early ophthalmic examination ruled out the
      possibility that cataract was due to age-related persistence of high ferritin
      levels in the lens and suggested that other factors may modulate the phenotype.
      CONCLUSION: cataract may appear early in hereditary hyperferritinaemia-cataract
      syndrome and this syndrome should be suspected and ferritin levels measured in
      all cases of cataract in children, even when the onset is in early infancy.

PMID- 12200612
TI  - Scene segmentation by spike synchronization in reciprocally connected visual
      areas. I. Local effects of cortical feedback.
AB  - To investigate scene segmentation in the visual system we present a model of two
      reciprocally connected visual areas using spiking neurons. Area P corresponds to
      the orientation-selective subsystem of the primary visual cortex, while the
      central visual area C is modeled as associative memory representing stimulus
      objects according to Hebbian learning. Without feedback from area C, a single
      stimulus results in relatively slow and irregular activity, synchronized only for
      neighboring patches (slow state), while in the complete model activity is faster
      with an enlarged synchronization range (fast state). When presenting a
      superposition of several stimulus objects, scene segmentation happens on a time
      scale of hundreds of milliseconds by alternating epochs of the slow and fast
      states, where neurons representing the same object are simultaneously in the fast
      state. Correlation analysis reveals synchronization on different time scales as
      found in experiments (designated as tower, castle, and hill peaks). On the fast
      time scale (tower peaks, gamma frequency range), recordings from two sites coding
      either different or the same object lead to correlograms that are either flat or
      exhibit oscillatory modulations with a central peak. This is in agreement with
      experimental findings, whereas standard phase-coding models would predict shifted
      peaks in the case of different objects.

PMID- 12200613
TI  - Scene segmentation by spike synchronization in reciprocally connected visual
      areas. II. Global assemblies and synchronization on larger space and time scales.
AB  - We present further simulation results of the model of two reciprocally connected
      visual areas proposed in the first paper [Knoblauch and Palm (2002) Biol Cybern
      87:151-167]. One area corresponds to the orientation-selective subsystem of the
      primary visual cortex, the other is modeled as an associative memory representing
      stimulus objects according to Hebbian learning. We examine the scene-segmentation
      capability of our model on larger time and space scales, and relate it to
      experimental findings. Scene segmentation is achieved by attention switching on a
      time-scale longer than the gamma range. We find that the time-scale can vary
      depending on habituation parameters in the range of tens to hundreds of
      milliseconds. The switching process can be related to findings concerning
      attention and biased competition, and we reproduce experimental poststimulus time
      histograms (PSTHs) of single neurons under different stimulus and attentional
      conditions. In a larger variant the model exhibits traveling waves of activity on
      both slow and fast time-scales, with properties similar to those found in
      experiments. An apparent weakness of our standard model is the tendency to
      produce anti-phase correlations for fast activity from the two areas. Increasing
      the inter-areal delays in our model produces alternations of in-phase and anti
      phase oscillations. The experimentally observed in-phase correlations can most
      naturally be obtained by the involvement of both fast and slow inter-areal
      connections; e.g., by two axon populations corresponding to fast-conducting
      myelinated and slow-conducting unmyelinated axons.

PMID- 12200614
TI  - Resonant spatiotemporal learning in large random recurrent networks.
AB  - Taking a global analogy with the structure of perceptual biological systems, we
      present a system composed of two layers of real-valued sigmoidal neurons. The
      primary layer receives stimulating spatiotemporal signals, and the secondary
      layer is a fully connected random recurrent network. This secondary layer
      spontaneously displays complex chaotic dynamics. All connections have a constant
      time delay. We use for our experiments a Hebbian (covariance) learning rule. This
      rule slowly modifies the weights under the influence of a periodic stimulus. The
      effect of learning is twofold: (i) it simplifies the secondary-layer dynamics,
      which eventually stabilizes to a periodic orbit; and (ii) it connects the
      secondary layer to the primary layer, and realizes a feedback from the secondary
      to the primary layer. This feedback signal is added to the incoming signal, and
      matches it (i.e., the secondary layer performs a one-step prediction of the
      forthcoming stimulus). After learning, a resonant behavior can be observed: the
      system resonates with familiar stimuli, which activates a feedback signal. In
      particular, this resonance allows the recognition and retrieval of partial
      signals, and dynamic maintenance of the memory of past stimuli. This resonance is
      highly sensitive to the temporal relationships and to the periodicity of the
      presented stimuli. When we present stimuli which do not match in time or space,
      the feedback remains silent. The number of different stimuli for which resonant
      behavior can be learned is analyzed. As with Hopfield networks, the capacity is
      proportional to the size of the second, recurrent layer. Moreover, the high
      capacity displayed allows the implementation of our model on real-time systems
      interacting with their environment. Such an implementation is reported in the
      case of a simple behavior-based recognition task on a mobile robot. Finally, we
      present some functional analogies with biological systems in terms of autonomy
      and dynamic binding, and present some hypotheses on the computational role of
      feedback connections.

PMID- 12200615
TI  - Computational method for muscle-path representation in musculoskeletal models.
AB  - This paper presents a new and efficient method to calculate the line-of-action of
      a muscle as it wraps over bones and other tissues on its way from origin to
      insertion. The muscle is assumed to be a one-dimensional, massless, taut string,
      and the surfaces of bones that the muscle may wrap around are approximated by
      cross-sectional boundaries obtained by slicing geometrical models of bones. Each
      cross-sectional boundary is approximated by a series of connected line segments.
      Thus, the muscle path to be calculated is piecewise linear with vertices being
      the contact points on the cross-sectional boundaries of the bones. Any level of
      geometric accuracy can be obtained by increasing the number of cross sections and
      the number of line segments in each cross section. The algorithm is
      computationally efficient even for large numbers of cross sections.

PMID- 12200616
TI  - Postural dynamics in maximal isometric ramp efforts.
AB  - Aglobal biomechanical model of transient push efforts is proposed where transient
      efforts are taken into consideration, with the aim to examine in greater depth
      the postural adjustments associated with voluntary efforts. In this context, the
      push effort is considered as a perturbation of balance, and the other reaction
      forces as a counter-perturbation which is necessary for the task to be performed
      efficiently. The subjects were asked to exert maximal horizontal two-handed
      isometric pushes on a dynamometric bar, as rapidly as possible. They were seated
      on a custom-designed device which measured global and partitive dynamic
      quantities. The results showed that the horizontal reaction forces and the
      horizontal displacement of the centre of pressure increased quasi-proportionally
      with the perturbation. In addition, it was established that vertical reaction
      forces increased at seat level whereas they decreased at foot level, resulting in
      minor vertical acceleration and displacement of the centre of gravity. On the
      contrary, the anteroposterior reaction forces increased both at foot and at seat
      levels. Based on a detailed examination of the various terms of the model, it is
      concluded that transient muscular effort induces dynamics of the postural chain.
      These observations support the view that there is a postural counter-perturbation
      which is associated with motor activity. More generally, the model helped to
      specify the effect of postural dynamic phenomena. It makes it possible to stress
      the importance of adherence at the contact level between the subject and the seat
      in the course of transient efforts.

PMID- 12200617
TI  - Functionality of divergence and convergence in a model of the insect olfactory
      system.
AB  - Recent studies have shown that the insect olfactory system uses a spatio-temporal
      encoding of odours in the population of projection neurons in the antennal lobe,
      and suggest that the information thus coded is spread across a large population
      of Kenyon cells in the mushroom bodies. At this stage, the temporal part of the
      code might be transformed into a spatial code, especially via the temporally
      sensitive mechanisms of paired-pulse facilitation and feedback inhibition with
      its possible associated rebound. We explore here a simple model of the olfactory
      system using a three-layer network of formal neurons, comprising a fixed number
      (three) of projection and inhibitory neurons, but a variable number of Kenyon
      cells. We show how enlarging the divergence of the network (i.e. the ratio
      between the number of Kenyon cells to the number of input - projection - neurons)
      alters the number of different output spatial states in response to a fixed set
      of spatio-temporal inputs, and may therefore improve its effectiveness in
      discriminating between these inputs. Such enlarged divergence also reduces the
      variation of this effectiveness among random realizations of the network
      connectivity. Our model shows that the discriminative effectiveness first
      increases with the divergence, and then plateaus for a divergence factor of
      approximately 20. The maximal average number of different outputs was 470.2,
      which was computed from some simulations with random realizations of connectivity
      and with a set of 512 possible inputs. The discriminative effectiveness of the
      network is sensitive to paired-pulse facilitation, and especially to inhibition
      with rebound.

PMID- 12200618
TI  - NACP/alpha-synuclein immunoreactivity in diffuse neurofibrillary tangles with
      calcification (DNTC).
AB  - Diffuse neurofibrillary tangles with calcification (DNTC) is a rare tangle
      predominant dementia, as well as one of the tauopathies lacking Abeta deposition.
      It is characterized by temporo-frontal lobar atrophy, Fahr-type calcification
      and, histopathologically, numerous neurofibrillary tangles in the limbic system
      and neocortex. Recently, accumulation of alpha-synuclein (alphaS), the precursor
      of the non-beta amyloid component (NAC) of Alzheimer's disease, has been shown in
      diverse neurodegenerative disorders, including Parkinson's disease, dementia with
      Lewy bodies, Alzheimer's disease, multiple system atrophy and parkinsonism
      dementia complex of Guam. To clarify whether alphaS accumulates in other
      neurodegenerative disorders, we investigated eight DNTC brains using
      immunohistochemistry and demonstrated remarkable alphaS deposition in the neurons
      and astrocytes in many anatomical regions. Abundant Lewy bodies were observed in
      the amygdala (seven cases) and hippocampus (seven cases), and, to a lesser
      degree, in the substantia nigra (six cases) and dorsal vagal nucleus (five
      cases). In the hippocampus, many Lewy neurites were distributed in the stratum
      oriens and stratum pyramidale in the CA2-3 and the subiculum. Furthermore,
      numerous NAC-positive astrocytes were detected in the hippocampus and temporal
      cortex. This investigation reveals that neurons and astrocytes are extensively
      involved in remarkable alphaS pathology in the DNTC brain, and that the alphaS
      pathology compounds the cardinal pathological features of tau pathology. These
      findings suggest that (1) DNTC shares a common pathophysiological background with
      Parkinson's disease, dementia with Lewy bodies, and multiple system atrophy in
      which abnormal alphaS aggregation is observed, and (2) there is an interaction
      between alphaS and tau pathology that does not involve amyloid in DNTC.

PMID- 12200619
TI  - Hyperphosphorylated tau deposition parallels prion protein burden in a case of
      Gerstmann-Straussler-Scheinker syndrome P102L mutation complicated with dementia.
AB  - Hyperphosphorylated tau (p-tau) deposition has been documented in a limited
      population of patients with Gerstmann-Straussler-Scheinker syndrome (GSS) with
      particular point mutations of the prion protein (PrP) gene. Although its
      pathogenesis is only poorly understood, p-tau in GSS is known to be identical to
      that in Alzheimer's disease (AD). We conducted immunohistochemical and
      quantitative image studies on the brain from a 44-year-old man with a 7-year
      history of dementia, diagnosed as having GSS with a point mutation of the PrP
      gene at codon 102 (GSS102), the commonest mutation in GSS. Severe spongiform
      degeneration and numerous PrP plaques were disclosed in the cerebral cortices and
      hippocampus, consistent with the diagnosis. However, rarely described in GSS102,
      prominent p-tau deposits as pretangles, neurofibrillary tangles and degenerating
      neurites were demonstrated adjacent to or around PrP plaques. beta-Amyloid
      protein (Abeta) plaques were generally sparse and appeared invariably to be of a
      diffuse type. Double-labeling immunohistochemistry yielded co-localization of p
      tau with PrP but not with Abeta. Most PrP plaques did not contain Abeta. These
      results excluded a diagnosis of concomitant AD. Quantitative analysis on a
      fractional area density of immunoreactive pixels demonstrated that burdens of PrP
      and p-tau but not Abeta were significantly correlated. These results suggest that
      p-tau deposition in this GSS102 is secondarily induced by PrP but not by Abeta
      (secondary tauopathy). Our study also suggests that p-tau deposition might be a
      more common phenomenon in long-standing GSS.

PMID- 12200620
TI  - Interstitial cells subjacent to the entorhinal region expressing somatostatin-28
      immunoreactivity are susceptible to development of Alzheimer's disease-related
      cytoskeletal changes.
AB  - Interstitial cells are isolated neurons located in the infracortical white matter
      that are known to express neuropeptides. Twenty-four cases selected for the
      absence, slight (Braak stages I-II), moderate (Braak stages III-IV), or serious
      degree (Braak stages V-VI) of cortical neurofibrillary pathology were studied for
      the presence of Alzheimer's disease-related abnormal tau in interstitial cells of
      the entorhinal region. AT8-immunoreactive white matter neurons were observed in
      all Braak stages of cortical neurofibrillary pathology. Both normal-appearing
      neurons and neurons with degenerative changes in the cellular processes were
      observed. Normal-appearing cells were predominantly found in stages I and II,
      whereas degenerative interstitial cells numerically increased from stage I
      onwards. The normal-appearing cells were medium-sized (10-25 micro m), with
      ovoid, fusiform, triangular or multipolar cell bodies, and showed an extensive
      dendritic field, which was oriented perpendicular to the direction of the
      perforant pathway. Since the morphology of the AT8-immunopositive normal
      appearing cells was similar to that reported on somatostatinergic interstitial
      cells subjacent to the entorhinal region, double-labeling with AT8 and anti
      somatostatin-28 (S309) was performed. All AT8-immunoreactive normal-appearing
      interstitial cells revealed co-staining with somatostatin-28 antiserum, whereas
      some of the AT8-immunopositive cells with degenerative processes reacted
      positively and others negatively with S309. In summary, a distinctive
      interstitial cell type characterized by extensive arborization oriented
      perpendicular to the course of the perforant pathway and showing somatostatin
      expression is susceptible to developing the Alzheimer's disease-related
      cytoskeletal changes. Progression in cytoskeleton change is accompanied by loss
      of somatostatin.

PMID- 12200621
TI  - Methylation of the p73 gene in gliomas.
AB  - The p73 gene encodes a protein structurally and functionally homologous to TP53,
      and maps to chromosomal band 1p36.33, where loss of heterozygosity has been
      observed in up to 90% of oligodendrogliomas and in 10-25% of diffuse
      astrocytomas. We assessed the methylation status of the CpG islands in the
      promoter region of the p73 gene by methylation-specific PCR in 117 glioma
      biopsies. Methylation was detected in 5 out of 28 (18%) glioblastomas and in 4/26
      (15%) anaplastic oligodendrogliomas (WHO grade III) but not in grade II
      oligodendrogliomas, low-grade diffuse astrocytomas (grade II), and anaplastic
      astrocytomas (grade III). To assess whether p73 methylation leads to loss of
      expression, we carried out reverse transcription-PCR and methylation-specific PCR
      in 10 glioblastoma cell lines. Two lines (U87MG and T98G) showed p73 methylation.
      U87MG had no unmethylated p73 (complete methylation), and showed loss of
      expression. T98G had methylated and unmethylated p73 (partial methylation), and
      retained p73 expression. A third cell line (LN-308) showed loss of p73 expression
      without p73 methylation. These results suggest that complete p73 methylation is
      associated with loss of expression, but that additional mechanisms may cause loss
      of p73 expression. Analysis of a polymorphic site in exon 2 further showed that
      p73 was mono-allelically expressed in 6 out of 7 primary gliomas with
      heterozygous GC/TA polymorphism.

PMID- 12200622
TI  - Motoneuron death in normal and spinal muscular atrophy-affected human fetuses.
AB  - The onset and sequence of motoneuron death in the lumbar part of spinal cord of
      seven control and five affected fetuses carrying deletion of exon 7 in the SMN
      gene were studied by light and electron microscopy. Naturally occurring
      motoneuron death in control fetuses was detected between 8 and 13 weeks of
      gestation. In affected fetuses motoneuron death was prolonged and also observed
      at 16 and 20 weeks of gestation. In addition, motoneurons in the affected fetuses
      displayed nuclear abnormalities as early as 16 weeks of gestation and the changes
      progressed as the affected fetuses developed and can be considered first signs of
      motoneuron degeneration.

PMID- 12200623
TI  - Up-regulation of cell division cycle (cdc) 2 kinase in neurons with early stage
      Alzheimer's disease neurofibrillary degeneration.
AB  - The major component of Alzheimer's disease (AD) neurofibrillary tangles (NFTs) is
      abnormally hyperphosphorylated tau aggregated as paired helical filaments (PHFs).
      Cell division cycle (cdc) 2 kinase is one of the main candidate kinases that
      phosphorylates normal tau in vitro at several sites seen in PHF-tau. Using brains
      staged according to Braak and Braak criteria, we investigated the role of cdc2 in
      neurofibrillary changes in the hippocampal formation, and the entorhinal and
      temporal cortices. Neurons with tangle-like inclusions positive for active cdc2
      were found to appear first in the Pre-alpha layer of the entorhinal cortex, and
      then extend to other brain regions co-incident with the progressive sequence of
      neurofibrillary changes. This predictable progressive pattern is not associated
      with amyloid. The intraneuronal accumulation of active cdc2 appeared to precede
      the deposition of PHF-tau phosphorylated at Ser 202/Thr 205 sites. These data are
      consistent with the notion that cdc2 might be involved in the abnormal
      hyperphosphorylation of tau and consequently aggregation of tau into PHF at an
      early stage and that increased cdc2 activity is not consequent to the deposition
      of beta-amyloid in AD brain.

PMID- 12200624
TI  - Induction of hematopoietic prostaglandin D synthase in hyalinated necrotic muscle
      fibers: its implication in grouped necrosis.
AB  - Prostaglandin (PG) D(2) exerts pro-inflammatory and anti-inflammatory functions
      under various pathological conditions. We found that the immunoreactivity of
      hematopoietic PGD synthase (HPGDS) appeared in necrotic muscle fibers, mainly in
      foci of grouped necrosis, in Duchenne's muscular dystrophy (DMD) and polymyositis
      (PM), but not in Becker's muscular dystrophy or in Fukuyama-type congenital
      muscular dystrophy. The HPGDS expression in DMD and PM was observed to be
      transient in hyalinated fibers at the early necrotic stage but not detected in
      opaque fibers, in fibers infiltrated by monocytes/lymphocyte, or in regenerating
      fibers. The immunoreactivities of a cytosolic form of phospholipase A(2) and
      cyclooxygenase-2, the upstream enzymes of the arachnoid acid cascade, were
      similarly observed in the HPGDS-positive fibers, suggesting that PGD(2) was
      produced in situ in those necrotic muscle fibers.

PMID- 12200625
TI  - Effects of intravenous immunoglobulins on T cell and oligodendrocyte apoptosis in
      high-dose antigen therapy in experimental autoimmune encephalomyelitis.
AB  - Intravenous immunoglobulins (IVIg) are purified preparations of immunoglobulins
      from plasma of healthy human donors containing polyclonal IgG and various
      immunomodulatory contaminants. IVIg may exert its therapeutic effect at several
      levels of the immune network. Antigen-specific therapy of adoptive transfer-(AT)
      EAE in Lewis rats leads to elevated serum levels of tumor necrosis factor-alpha
      (TNF-alpha). TNF-alpha release at sites of inflammation increased apoptosis of
      autoaggressive T cells in spinal cord in situ and oligodendrocyte apoptosis. In
      addition, autoinflammatory T cells in liver were destroyed and caused liver
      damage by TNF-alpha release. To explore a possible neutralizing effect of IVIg on
      TNF-alpha secreted by antigen-specific T cells, we analyzed T cell and
      oligodendrocyte apoptosis as well as liver damage in rats that had been injected
      with myelin basic protein (MBP) and co-treated intravenously with human IVIg. As
      in our earlier studies, we found that TNF-alpha serum levels were raised by
      antigen therapy and decreased with concomitant IVIg administration. Using IVIg
      treatment, antigen-induced T cell apoptosis in inflamed spinal cord and liver of
      MBP/IVIg-treated animals was significantly reduced compared to control rats
      treated with MBP/albumin. T cell apoptosis decreased to levels observed in EAE
      rats receiving albumin only. In addition, serum levels of liver enzymes were
      raised after MBP/albumin administration and decreased by co-treatment with IVIg,
      indicating protection of hepatocytes by the neutralization of TNF-alpha. In
      contrast, oligodendrocyte apoptosis in animals receiving MBP/IVIg was
      significantly higher than in EAE controls. This indicates that IVIg may have
      different tissue-specific effects. Besides neutralization of TNF-alpha-mediated
      cell death, IVIg may also interfere with the network of local immune cells, thus
      modulating survival of glial cells.

PMID- 12200626
TI  - Reduced neuronal nitric oxide synthase (NOS1) antigen in sacral motor neurones in
      motor neurone disease.
AB  - Immunocytochemistry and microdensitometry applied under standardised conditions
      were used to evaluate neuronal nitric oxide synthase (NOS1) antigen in segmental
      motor neurones (MN) of six subjects without neurological disease, nine subjects
      with sporadic motor neurone disease (MND) and five with neurological disease
      unrelated to MND. No significant segmental differences in levels of NOS1
      immunoreactivity occurred between the two control groups, and differences between
      cervical, thoracic and lumbar MN of the three subject groups were not
      significant. However, MND patients showed a significantly reduced level of NOS1
      immunoreactivity in the Onuf's nucleus (ON); this is discussed in relation to
      neuroprotection and the relative sparing of ON in MND.

PMID- 12200627
TI  - Tau accumulation in astrocytes in progressive supranuclear palsy is a
      degenerative rather than a reactive process.
AB  - Tau-immunoreactive astrocytes in progressive supranuclear palsy (PSP) have a
      distinctive morphology and are referred to as tufted astrocytes (TA). We
      hypothesized that TA may be a degenerative change in reactive astrocytes. To test
      this hypothesis we examined the relationship of TA to gliosis in PSP. We first
      examined the distribution of gliosis [glial fibrillary acid protein (GFAP)
      positive astrocytes], TA, neurofibrillary tangles (NFT) and pretangles in brain
      sections of neuropathologically pure PSP cases. Second, we examined PSP cases
      complicated by infarcts or Alzheimer's disease, since these cases would have
      reactive astrocytes associated with lesions. We used double immunostaining for
      GFAP and tau for cases with vascular lesions, and triple immunostaining for GFAP,
      tau and beta-amyloid protein for sections with senile plaques. There was no
      correlation between the distribution of gliosis and TA, with gliosis prominent in
      globus pallidus and subthalamic nucleus, and TA prominent in motor cortex and
      striatum. On the other hand, gliosis paralleled the distribution of NFT, but not
      the distribution of pretangles, suggesting that NFT contributes to gliosis in
      PSP. Although reactive astrocytes were present around infarcts and senile
      plaques, TA were not associated with these lesions. Tau accumulation in
      astrocytes in PSP was not preferential to (and was actually independent of)
      reactive astrocytes. This is consistent with the notion that tau accumulation in
      astrocytes is a degenerative rather than reactive process. Unlike NFT, astrocytic
      degeneration does not seem to contribute to gliosis or neuronal loss in PSP, and
      its clinical significance remains unclear.

PMID- 12200629
TI  - Neuronal migration disturbance and consequent cytoarchitecture in the cerebral
      cortex following transplacental administration of methylmercury.
AB  - To understand the effects of methylmercury (MeHg) on neuronal migration in the
      developing cerebral cortex, we performed double administrations of MeHg and 5
      bromo-2-deoxyuridine (BrdU) to pregnant rats on different embryonic days (E11,
      E13, E16 or E21). Histopathological examination of a proportion of the offspring
      on postnatal day 28 revealed no apparent cytoarchitectural abnormalities in the
      primary motor and primary somatosensory cortices of the cerebrum. Morphometric
      analysis revealed no significant differences in total neuron population in either
      of these areas, and no differences in subpopulations of cells in any of the
      cortical layers, between any of the MeHg-exposed groups and the control animals.
      However, BrdU immunohistochemistry revealed an abnormally widespread distribution
      of the labeled cells throughout cortical layers II-VI of offspring exposed to
      MeHg on E16 and E21, indicating disruption of the inside-out pattern of neuronal
      migration. We examined one aspect of cell-fate determination by applying
      immunohistochemistry with antibodies against calbindin, parvalbumin, calretinin,
      and gamma-aminobutyric acid, but found no differences in the topographic
      distributions of the antibody-labeled cells in the cortex between the controls
      and the MeHg-exposed offspring. These results suggest that it is the extrinsic
      circumstances - rather than the timing of neuron generation - that regulates the
      expression of these proteins.

PMID- 12200628
TI  - Mutational and expression analysis of the reelin pathway components CDK5 and
      doublecortin in gangliogliomas.
AB  - Gangliogliomas represent highly differentiated glioneuronal tumors frequently
      occurring in young patients with focal epilepsies. Dysplastic neurons are a
      neuropathological hallmark of this neoplasm. Here, we have analyzed two major
      components of the reelin pathway associated with neuronal migration and cortical
      cytoarchitecture in gangliogliomas, i.e., cyclin-dependent kinase 5 (CDK5) and
      doublecortin (DCX). The genomic structure of human CDK5 was identified by an " in
      silico" cloning approach using the "high throughput genomic sequencing" (htgs)
      databank, NCBI BLAST 2.1. DNA sequence analysis of CDK5 and DCX was carried out
      in tissue samples obtained from 23 patients and compared with control DNA from
      non-affected individuals ( n=100). For gene expression analysis of CDK5 and DCX,
      a quantitative real time reverse transcription-PCR TaqMan assay was used with
      mRNA from gangliogliomas ( n=22) and non-lesional central nervous tissue control
      tissue ( n=7). The human CDK5 gene is located on chromosome 7q36 and contains 12
      exons. Its coding sequence reveals 90.1% homology to the mouse counterpart. A
      novel pseudogene of CDK5 was found on chromosome 8. While the mutational analysis
      of CDK5 and DCX did not reveal any sequence alterations in gangliogliomas, a
      lower expression was observed for both genes in tumor compared to control tissue
      samples. The present data indicate that mutations of CDK5 and DCX genes are not
      involved in the development of gangliogliomas. A novel pseudogene on chromosome 8
      has to be taken into account for future studies on CDK5.

PMID- 12200630
TI  - Doublecortin immunoreactivity in giant cells of tuberous sclerosis and focal
      cortical dysplasia.
AB  - Cerebral cortical lesions of tuberous sclerosis (TSC) and focal cortical
      dysplasia (FCD) show disturbances in laminar architecture and cellular
      differentiation. We immunohistochemically studied the expression of doublecortin,
      a fetal neuronal protein that regulates neuronal migration, in the surgical
      specimens of five TSC and eight FCD patients. In both TSC and FCD, bizarre giant
      cells showed a variable degree of doublecortin immunoreactivity. Both cytomegalic
      neurons and balloon cells were positive. The staining tended to be more intense
      in TSC than in FCD, although there were exceptional cases in both groups.
      Doublecortin immunoreactivity of normal-sized neural cells was restricted to a
      small number of astrocytes, and comparable to that in control patients. The
      persistent expression of doublecortin by giant cells in the postnatal cerebrum is
      additional evidence of abnormal differentiation, which may be relevant to the
      pathogenesis of cortical disarray in TSC and FCD.

PMID- 12200631
TI  - Argyrophilic grain disease and Alzheimer's disease are distinguished by their
      different distribution of tau protein isoforms.
AB  - Prominent neuronal and glial tau filamentous inclusions are hallmarks of
      neurodegenerative tauopathies, among them Alzheimer's disease (AD), progressive
      supranuclear palsy (PSP), corticobasal degeneration (CBD), Pick's disease (PiD),
      and argyrophilic grain disease (AgD). AgD is a late onset dementia in which
      pathologically aggregated tau proteins are found in limbic structures in the
      shape of distinct argyrophilic grains and coiled bodies. Until now tau protein
      deposits in AgD have not been assessed biochemically. We therefore decided to
      investigate the electrophoretic profile of pathological tau protein as well as
      the tau protein isoform composition of filamentous inclusions in AgD cases. A
      distinct pathological tau doublet at 64 and 69 kDa and a minor 74-kDa band was
      obtained in two AgD cases with only very mild concomitant AD pathology (Braak
      stage I), while in two AgD cases with moderate AD pathology (Braak stage II and
      III, respectively), an additional minor band at 60 kDa was detected. Thus, the
      pathological tau profile (PTP) in pure AgD cases differs from both the PTPs in AD
      (tau triplet at 60, 64 and 69 kDa, minor band at 74 kDa) and PiD (major tau
      doublet at 60 and 64 kDa, minor band at 69 kDa) but not from those in PSP and
      CBD. Using a two-dimensional gel electrophoresis approach anti-exon 10 antiserum
      strongly stained the AgD doublet and the minor 74-kDa band, while anti-exon 2 and
      3 antisera only faintly stained the 69- and the minor 74-kDa component, thus
      suggesting that pathological tau aggregates in AgD are mainly made of four-repeat
      (4R) tau isoforms. Furthermore, in contrast to earlier immunohistochemical
      studies, we now show biochemically that Ser262 indeed is phosphorylated in the
      PTP of AgD. Finally, expression of normal tau protein was not found to be altered
      in AgD. Altogether, our results demonstrate that AgD is characterized by a major
      tau doublet that is distinct from AD and PiD. AgD, however, shares the
      pathological tau doublet (64 and 69 kDa) as well as the predominance of 4R tau
      isoforms with CBD and PSP.

PMID- 12200633
TI  - Infarct scar as living tissue.
AB  - Infarct scar tissue has long been considered inert (acellular, composed simply of
      fibrillar collagen) and whose function is simply to restore structural integrity
      to infarcted myocardium and to provide tensile strength that prevents tissue
      rupture. Technologies of cellular and molecular biology have altered this
      perspective. Infarct scar is now recognized as living tissue: composed of a
      persistent population of fibroblast-like cells whose ongoing activity includes a
      regulation of collagen turnover and scar tissue contraction and which are
      nourished by a neovasculature. Herein we briefly review these various components
      of the infarct scar that provide for its dynamic nature and which is relevant to
      today's interest in preventing heart failure through a rebuilding (regrowing) of
      myocardial tissue at the infarct size.

PMID- 12200632
TI  - Neural transformation in a pituitary corticotroph adenoma.
AB  - A pituitary mass was removed by the transsphenoidal approach from a 63-year-old
      man with the clinical history and laboratory findings characteristic of Cushing's
      disease with partial hypopituitarism. Histological, immunohistochemical,
      ultrastructural and immunoelectron microscopic investigation demonstrated a
      periodic acid-Schiff-positive, adrenocorticotropic hormone (ACTH)-immunoreactive,
      pituitary corticotroph adenoma with the formation of neural tissue resembling
      neuropil within the tumor. The neural elements showed immunopositivity for
      neurofilament protein and ACTH, but were immunonegative for other
      adenohypophysial hormones and for corticotropin-releasing hormone. Although the
      molecular mechanism accounting for neural transformation in this corticotroph
      adenoma remained obscure, based on the clinical, histological and morphological
      findings it appears that formation of neural tissue most likely indicate a
      favorable prognosis.

PMID- 12200634
TI  - Lentiviral vectors for delivery of genes into neonatal and adult ventricular
      cardiac myocytes in vitro and in vivo.
AB  - Vectors based on lentiviruses such as human immunodeficiency virus (HIV) type-1
      have many advantages for gene therapy, including the ability to infect non
      dividing cells, long-term transgene expression and the absence of induction of an
      inflammatory/immune response. This study was initiated to determine whether
      lentiviruses would efficiently transfer genes to both neonatal and adult cardiac
      cells in culture and, by direct injection, to the heart in vivo. A three-plasmid
      expression system, including a packaging defective helper construct, a plasmid
      coding for a heterologous (VSV-G) envelope protein and a vector construct
      harboring reporter genes - E-GFP (enhanced green fluorescent protein) and puro
      (puromycin-resistance protein) was used to generate pseudotyped HIV-1 particles
      by transient transfection of human embryonic kidney 293T cells. We demonstrated
      efficient gene transfer into neonatal and adult cardiac myocytes in vitro and
      identified conditions in which virtually 100 % of cultured neonatal and 70 % of
      adult cardiac myocytes express the reporter gene. Transduction of adult cardiac
      myocytes with high titre lentiviral vectors did not affect the cell number,
      morphology or viability compared to untransduced cells. We delivered HIV-1-based
      vectors to the intact heart by direct injection. Hearts transduced with
      pseudotyped HIV-1 vectors showed levels of transgene expression comparable to
      that achieved by adenovirus vectors. This study demonstrates for the first time
      that lentivirus-based vectors can successfully transduce adult cardiomyocytes
      both in vitro and in vivo, and opens up the prospect of lentivirus-based vectors
      becoming an important gene delivery system in the cardiovascular field.

PMID- 12200635
TI  - Selectin-mediated rolling of neutrophils is essential for their activation and
      retention in the reperfused coronary system.
AB  - Neutrophil adhesion to coronary endothelium is a key event for cardiac
      reperfusion injury. Adhesion is proposed to be a multi-step event, consisting of
      selectin-mediated rolling, chemotactic activation, and subsequent integrin
      mediated firm attachment. However, it is not clear whether this sequence also
      occurs in the coronary circulation with its unique hemodynamic properties
      (turbulent flow, flow reversal). We have studied neutrophil adhesion in the
      coronary system of isolated perfused guinea pig hearts under basal and
      reperfusion conditions (15 min global ischemia). Adhesion was manipulated by an
      anti-CD18 antibody (blocking firm adhesion) and fucoidin (reducing rolling).
      Neutrophil behavior during coronary passage was assessed by measurement of CD11b
      expression, forward scatter (FSC, indicating polarization), and sideward scatter
      (SSC, measure for granularity) via flow cytometry. Adhesion rose from 21 %
      (basal) to 35 % after ischemia. Anti-CD18 decreased adhesion to 11 % and 14 %,
      respectively; fucoidin altered only the postischemic increase (23 %). CD11b was
      unchanged by passage through the non-ischemic coronaries, but rose
      postischemically (139 % increase). CD18 blockade did not reduce the postischemic
      rise of CD11b, while fucoidin was inhibitory (24 % increase). FSC did not differ
      between controls and ischemic hearts in any group, while SSC decreased most in
      postischemic hearts after CD18 blockade. Blockade of rolling and of firm
      attachment both reduce neutrophil retention, while only inhibition of rolling
      reduces intracoronary activation. Thus, rolling seems to be mandatory for
      endothelial-leukocyte communication in the coronary system.

PMID- 12200636
TI  - Opening of ATP-sensitive potassium channels causes generation of free radicals in
      vascular smooth muscle cells.
AB  - Recent evidence suggests that opening of mitochondrial K(ATP) channels in cardiac
      muscle triggers the preconditioning phenomenon through free radical production.
      The present study tested the effects of K(ATP) channel openers in a vascular
      smooth muscle cell model using the fluorescent probe MitoTracker (MTR) Red trade
      mark for detection of reactive oxygen species (ROS). Rat aortic smooth muscle
      cells (A7r5) were incubated with 1 micro M reduced MTR (non-fluorescent) and the
      MTR oxidation product (fluorescent) was quantified. Thirty-minute pretreatment
      with either diazoxide (200 micro M) or pinacidil (100 micro M), both potent
      mitochondrial K(ATP) channel openers, increased fluorescent intensity (FI) to 149
      and 162 % of control (p < 0.05 for both), respectively, and the K(ATP) channel
      inhibitor 5-hydroxydecanoate (5 HD) blocked it. Valinomycin, a potassium
      selective ionophore, raised FI to 156 % of control (p <: 0.05). However, 5 HD did
      not affect the valinomycin-induced increase in FI. Inhibition of mitochondrial
      electron transport (myxothiazol) or uncoupling of oxidative phosphorylation
      (dinitrophenol) also blocked either valinomycin- or diazoxide-induced increase in
      FI, and free radical scavengers prevented any diazoxide-mediated increase in
      fluorescence. Finally the diazoxide-induced increase in fluorescence was not
      blocked by the PKC inhibitor chelerythrine, but was by HMR 1883, a putative
      surface K(ATP) channel blocker. Thus opening of K(ATP) channels increases
      generation of ROS via the mitochondrial electron transport chain in vascular
      smooth muscle cells. Furthermore, a potassium-selective ionophore can mimic the
      effect of putative mitochondrial KATP channel openers. We conclude that potassium
      movement through KATP directly leads to ROS production by the mitochondria.

PMID- 12200637
TI  - A model of closed chest regional myocardial infarction in the rabbit: a
      clinically relevant in vivo assay system of post-infarction remodelling.
AB  - Coronary artery ligation is the standard technique to induce regional myocardial
      infarction in small animal models. However, opening the chest and incising the
      pericardium independently influence post-MI remodelling. Our purpose was to
      develop and characterize a novel closed chest model of regional myocardial
      infarction (MI) in the rabbit of increased clinical relevance. Coronary
      angiography was performed percutaneously in New Zealand White Rabbits (NZW) using
      pre-formed catheters. A 0.36 mm thrombogenic coil was positioned in the
      circumflex artery to induce closed chest MI. Of rabbits undergoing coil
      deployment 40 % survived until day 100. Rabbits were classified as small MI (n =
      5), moderate MI (n = 6) and large MI (n = 6) < 15 %, 15 - 30 %, > 30 % of LV
      myocardial volume respectively) or sham controls (n=11). Transthoracic
      echocardiographic images were obtained 0, 3, 5, 7, 14, 28, 60, 100 days post
      procedure. At day 100, LVEDP was measured before and after plasma substitute
      infusion. Hearts were subsequently excised and chamber stiffness (Kc) was derived
      from the passive pressure-volume relationship. Cardiac weight, dimensions and MI
      as a percentage of LV volume (MI%) were also recorded. Differences in percentage
      fractional shortening (%FS) were apparent from day 14. %FS was reduced in rabbits
      with large and moderate MI compared to controls (day 100, p < 0.005 and p < 0.05,
      respectively). LVEDP was increased in large and moderate MI compared to small MI
      and controls (26 mmHg +/- 6 and 21 mmHg +/- 5 vs. 9 mmHg +/- 1 and 7 mmHg +/- 3 p
      < 0.005); these differences were maintained during plasma substitute infusion. Kc
      in large MI was significantly less than moderate MI, small MI or control (all p <
      0.05). Direct morphometric measurements distinguished between all groups.This
      study provides the first description of post-infarction remodelling after
      coronary artery occlusion where the pericardium remains intact in a small animal
      model. We believe it may provide a more physiologically and clinically relevant
      in vivo assay system of left ventricular dysfunction after myocardial infarction.

PMID- 12200638
TI  - Angiotensin inhibition and coronary autoregulation in a canine model of LV
      hypertrophy.
AB  - In humans with hypertension and LV hypertrophy, beneficial effects of angiotensin
      inhibition may be associated with preserved autoregulatory capacity. We studied
      the effect of acute angiotensin converting enzyme (ACE) inhibition on coronary
      autoregulatory pressure-flow relations and transmural distribution of blood flow
      in sham and LV hypertrophy dogs. Heart/body weight ratio increased (p = 0.001)
      from 5.5 +/- 0.7 in sham to 6.9 +/- 0.5 in LV hypertrophy dogs. The lower
      coronary pressure limit (LPL) on the pressure-flow relation was 47 +/- 2 mmHg in
      sham and 57 +/- 6 mmHg (p = 0.001) in LV hypertrophy dogs; after acute ACE
      inhibition the LPL was reduced to 40 +/- 5 mmHg and 49 +/- 6 mmHg (p = 0.001),
      respectively. Transmural distribution of blood flow was preserved at the LPL in
      both groups before and after acute ACE-inhibition. Concomitant blockade of
      prostaglandin and nitric oxide release and bradykinin catabolism had no
      additional effects on the LPL and distribution of blood flow. After acute ACE
      inhibition in LV hypertrophy dogs, distribution of blood flow across the LV wall
      was preserved and subendocardial vascular reserve was maintained even though the
      LPL was significantly lower. Preservation of autoregulatory capacity by ACE
      inhibitors contributes to beneficial outcome in patients with hypertension and LV
      hypertrophy.

PMID- 12200639
TI  - Endogenous nitric oxide regulates right coronary blood flow during acute
      pulmonary hypertension in conscious dogs.
AB  - This study investigated the role of nitric oxide (NO) in the control of right
      coronary (RC) blood flow at rest and during acute pulmonary hypertension.
      Experiments were performed in seven chronically instrumented, conscious dogs. NO
      synthesis was inhibited by systemic administration of N(omega)-nitro-L-arginine
      (LNA, 35 mg/kg). Inflation of a balloon in the main pulmonary artery raised right
      ventricular (RV) peak systolic pressure from 34 +/- 2 to 47 +/- 3 mmHg before LNA
      and from 37 +/- 2 to 47 +/- 3 mmHg after LNA, but did not affect mean systemic
      arterial pressure. RV O(2) consumption (MVO(2)) increased from 4.4 +/- 0.7 to 6.1
      +/- 0.7 ml/min/100 g. 82 % of the elevated RV MVO(2) was provided by RC blood
      flow, which increased from 46 +/- 7 to 61 +/- 8 ml/min/100 g. After LNA, resting
      RV MVO(2) and RC flow fell. RC venous PO(2) fell, but RV lactate uptake was not
      altered. During pulmonary hypertension, the increase in RC blood flow was blunted
      by LNA, so that only 66 % of the elevated RV MVO(2) was supplied by increased RC
      flow. Analysis of O(2) supply variables as functions of RV MVO(2) further
      demonstrated a significant role of NO in regulating RC flow at rest and during
      moderate pulmonary hypertension. Conclusions NO is required for the RC hyperemic
      response to acute pulmonary hypertension as well as for normal resting RC blood
      flow. After blockade of NO synthesis, RV O(2) supply at rest and during pulmonary
      hypertension was sustained by increased RV O(2) extraction.

PMID- 12200640
TI  - Impaired coronary flow and left ventricular dysfunction after mechanical
      recanalization in acute myocardial infarction: role of neurohumoral activation?
AB  - BACKGROUND: Reopening of the infarct-related coronary artery is the treatment of
      choice in the clinical setting of acute myocardial infarction. Nevertheless the
      removal of the total occlusion obtained either by thrombolysis or by primary
      angioplasty is followed by the ischemia/reperfusion sequelae. One of many
      proposed mechanisms playing a role in ischemia/reperfusion damage is a persistent
      increase in vasoconstrictor tone, which reduces cardiac function and impairs
      myocardial blood flow during primary percutaneous coronary intervention in acute
      myocardial infarction (PAMI). METHODS: To investigate early neurohumoral changes
      during PAMI we enrolled 18 patients, who were collated to 13 patients with stable
      angina undergoing elective PTCA. To evaluate angiotensin II (AngII), endothelin-1
      (ET-1), vasopressin (AVP), norepinephrine (NE), troponin T (TNT),
      creatinephosphate kinase (CPKM) and isoenzyme MB (CPKMB), we collected blood from
      the pulmonary artery before and immediately after the infarct-related artery
      (IRA; TIMI 0 --> 2-3) or culprit lesion revascularization. Hemodynamic and
      angiographic LV-function parameters were compared to biochemical data. Corrected
      TIMI-frame count (CTFC) was used as an index of coronary blood flow and
      correlated to the biochemical measurements. RESULTS: CTFC in the IRA correlated
      inversely (p = 0.03; r = -0.51) with left ventricular ejection fraction measured
      after 10 days, and positively (p = 0.03; r = 0.54) with the maximal amount of LDH
      released after onset of AMI. There was an abrupt and long lasting rise in ET-1
      (+65 %; p < 0.001) and an instant short lasting increase in AVP (+37 %; p <
      0.05), whereas NE concentrations were elevated prior to PAMI and remained
      elevated during reperfusion. Correlations with CTFC were found for ET-1 (p =
      0.01; r = 0.61) and NE (p = 0.01; r = 0.58) during reperfusion. The extent of
      left ventricular dysfunction correlated with the concentrations of AVP and NE
      during reperfusion. CONCLUSIONS: There is evidence for a distinct pattern of
      neurohumoral activation during early reperfusion in acute myocardial infarction.
      In particular, we documented substantial increases in AVP and ET-1. Left
      ventricular wall-stress appears to be involved in the release of AVP. Elevated
      levels of ET-1 and NE are associated with impaired angiographic reperfusion and
      increased myocardial damage after mechanical recanalization.

PMID- 12200641
TI  - Immunocytochemical evidence for inducible nitric oxide synthase and
      cyclooxygenase-2 expression with nitrotyrosine formation in human hibernating
      myocardium.
AB  - BACKGROUND: Myocardial hibernation may result from repetitive episodes of
      transient ischaemia leading to prolonged dysfunction. Inducible nitric oxide
      synthase (iNOS) expression has been demonstrated in animals following brief, non
      lethal ischaemia-reperfusion injury. We therefore, hypothesised that in human
      hibernating myocardium: 1). iNOS would be present; 2). the reaction of nitric
      oxide and superoxide would form the strong oxidant peroxynitrite; 3) that this
      process would be accompanied by the expression of cyclooxygenase-2 (Cox-2) which
      interacts with NOS and whose products could further affect myocardial function.
      METHOD AND RESULTS: In sixteen patients with coronary artery disease (CAD), left
      ventricular biopsies were obtained from chronically dysfunctional segments
      subtended by a stenotic artery (> 75 %) and shown to be viable by (18)F
      fluorodeoxyglucose positron emission tomography. Comparison was made with
      myocardial biopsies (n = 8) from normally contracting myocardium in patients
      undergoing coronary surgery, from unused transplant donors and at post-mortem.
      Regional wall motion score improved in all patients 6 months post
      revascularisation (from 2.7 +/- 0.7 to 1.5 +/- 0.5; p < 0.001), confirming
      hibernation. Immunocytochemistry localized reactivity to iNOS, Cox-2 and
      nitrotyrosine (a marker of peroxynitrite formation) to cardiomyocytes from
      hibernating segments. No difference in reactivity to endothelial NOS was seen
      between hibernating and control cardiomyocytes. CONCLUSION: Cox-2 and iNOS are co
      expressed in hibernating myocardium with nitrotyrosine suggesting nitric oxide
      production and peroxynitrite formation. We propose that this is secondary to
      ischaemia-reperfusion and that the products of these enzymes may have
      consequences for myocardial contractile function and survival.

PMID- 12200642
TI  - Percutaneous radiofrequency treatment of osteoid osteoma.
AB  - Osteoid osteoma is a small osteogenic tumor usually found in the lower extremity
      of children and young adults. Although these lesions are benign and rarely
      progress, they present distinctive pain symptoms that frequently require medical
      intervention. This article reviews surgical, medical, and percutaneous techniques
      for treatment of osteoid osteoma, emphasizing the value of percutaneous
      radiofrequency treatment.

PMID- 12200643
TI  - Conditional gene inactivation using cre recombinase.

PMID- 12200644
TI  - Monitored impact loading of the hip: initial testing of a home-use device.
AB  - Many studies have been done involving exercise, impact loading, and the effect on
      BMD. In some of these studies, particularly those involving outpatient activity,
      compliance and the specific parameters of an individual's impact loading have
      been difficult to monitor effectively. In this study, an individual, home-use
      platform was used to record daily, specific, and reproducible impact forces
      generated during a heel drop exercise. At three centers over 24 months, we
      conducted a randomized, prospective study of 157 osteoporotic and osteopenic
      women, aged 60-85 years. A total of 99 patients used the home Osteocare device
      (OrthoGenesis Incorporated, Northborough, Massachusetts USA) to generate a
      reproducible and specific daily impact program (active group). Controls (32)
      performed a similar motion on the unit but without trying to trigger an impact
      force (sham group), and 26 patients did no prescribed heel drop exercise (control
      group). All groups had the same calcium and vitamin D supplementation. Hip DXA
      was performed at baseline and every 6 months during the entire study duration.
      Compliance with the 3-5 min routine was high, and patients were able to
      consistently achieve the specific targeted impact range. Pooled BMD results
      showed no significant differences between groups in overall BMD measurements.
      However, a classification model that looked at individual site-specific BMD
      changes showed that more than 75% of the active group responded (versus 62% for
      both the sham and the control groups) by maintaining or increasing site-specific
      hip BMD over the 2-year trial. In fact, at the end of the study, 45% of the
      actives were gainers versus 12% and 22% in the sham and control groups,
      respectively. This study suggests that hip BMD may be maintained through a brief,
      safe, at-home, monitored impact loading program.

PMID- 12200645
TI  - Bone turnover in children and adolescents with McCune-Albright syndrome treated
      with pamidronate for bone fibrous dysplasia.
AB  - Bone fibrous dysplasia is one of the main features of McCune-Albright syndrome, a
      rare genetic condition caused by constitutive activating mutations of Gs-protein
      and defined by skin dysplasia, bone fibrous dysplasia, and autonomous multiple
      endocrinopathies. Raised serum alkaline phosphatase (ALP) and urinary
      hydroxyproline levels indicating bone metabolic hyperactivity have been reported
      in these patients. Encouraging therapeutic results have been achieved, mainly in
      adults, with pamidronate, an aminobisphosphonate. In this study we investigate
      newer bone metabolic indices in a cohort of 11 children and adolescents treated
      with pamidronate. Tenfold increases of bone ALP and urinary pyridinoline cross
      links were found and osteocalcin levels were twofold higher compared with
      reference values. After treatment, significant decreases in bone ALP and cross
      links (Wilcoxon test P < 0.06) were found. Bone mineral density (BMD)
      significantly increased during treatment. There were signs of radiological
      healing as thickening of the cortical bone was found in some cases.

PMID- 12200646
TI  - Short-term omeprazole treatment does not influence biochemical parameters of bone
      turnover in children.
AB  - Gastric proton pump inhibitors are widely used in the treatment of dyspeptic
      problems and for the eradication of H. pylori infection. Data are not available
      on whether omeprazole, a representative of proton pump inhibitors, influences the
      function of osteoclastic H+-pump in children. We studied the impact of short-term
      omeprazole administration on the biochemical parameters of bone turnover in
      pediatric patients. Urinary calcium excretion, serum total alkaline phosphatase
      activity, collagen type 1 crosslinked C-telopeptide, and osteocalcin levels were
      determined in 34 children [20 girls (9 prepubertal) and 14 boys (6 prepubertal)]
      before and after 2 weeks of omeprazole treatment at a dose of 20 mg/day. The
      measured parameters were within the healthy reference range in each patient. None
      of them altered during the study in any age or in any gender. We conclude that
      omeprazole, at a dose of 20 mg/day, does not significantly influence the
      investigated biochemical parameters of osteoclast and osteoblast function in
      pediatric patients.

PMID- 12200647
TI  - Assessment of the bone status of Nigerian children and adolescents with sickle
      cell disease using calcaneal ultrasound and serum markers of bone metabolism.
AB  - Growth and skeletal maturation are impaired in sickle cell disease (SCD). SCD is
      also associated with decreased bone mineral density (BMD) as determined by dual X
      ray and photon absorptiometry. Quantitative ultrasound (US), which is as good a
      predictor of fracture as absorptiometry, provides additional information about
      bone architecture and elasticity. It is not known if the quantitative US
      parameters, broadband ultrasound attenuation (BUA) and speed of sound (SOS), are
      affected in children and adolescents with SCD. We therefore compared the bones of
      80 children with SCD in Nigeria to those of age- and gender-matched controls
      using calcaneal ultrasound and the serum bone markers N-telopeptide of type1
      collagen (NTx) and bone-specific alkaline phosphatase (BSAP), which are
      indicators of bone resorption and formation, respectively. BUA, which is
      reflective of BMD, was significantly lower for both the male and female SCD
      subjects compared with controls (86 vs 113 dB/MHz, P < 0.001 and 87 vs 100
      dB/MHz, P < 0.001, respectively). However, SOS, which is more indicative of bone
      elasticity, was significantly different only for the male SCD subjects. Both NTx
      and BSAP were significantly reduced in the serum of the male and female SCD
      subjects. Correlations between BUA and serum NTx were found for both female
      controls and SCD subjects (r = 0.58, P < 0.001 and r = 0.32, P = 0.05,
      respectively), but not for the male subjects or controls. Significant
      correlations between BUA and BSAP were observed only for the female controls. In
      summary, we have shown that US analysis, in combination with serum markers of
      bone metabolism, can be used to distinguish bone development in children with SCD
      from that of nonaffected controls.

PMID- 12200648
TI  - Is it necessary to screen for celiac disease in postmenopausal osteoporotic
      women?
AB  - Decreased bone mass is a frequent finding in celiac patients, and subclinical
      celiac disease (CD) appears to be unusually overrepresented among patients with
      idiopathic osteoporosis. Since silent CD may be more common than previously
      believed, it has been suggested that all osteoporotic patients should be checked
      for occult CD. The aim of this study was to explore the prevalence of CD in a
      well-defined population of postmenopausal osteoporotic women. We evaluated 127
      consecutive postmenopausal patients (mean age: 68 years; range: 50-82 years) with
      verified osteoporosis. The observed prevalence of CD in this group was compared
      to that observed in a group of 747 women recruited for a population-based study.
      The screening algorithm used to diagnose CD was based on a 3-level screening
      using type IgA and IgG antigliadin antibodies (AGA) in all the patients (1st
      level) followed by antiendomysial antibodies (EmA) and total IgA (2nd level) of
      samples testing positive, and intestinal biopsy of positive cases (3rd level). At
      the end of the serological screening, only 1 of 127 osteoporotic women was
      eligible for jejunal biopsy showing a characteristic celiac flat mucosa
      (prevalence 7.9 x 1,000; 95% CI 0.2-43.1). In addition, CD was diagnosed in 6 of
      747 women of the population-based study (prevalence: 8.0 x 1,000; 95% CI 3.3
      18.3). There was no significant difference between the two groups. Therefore, our
      study showed that the prevalence of CD in postmenopausal osteoporotic women was
      lower than that reported in previous studies and similar to that of the general
      population. In conclusion, although the relatively small size of the group tested
      does not allow us to be conclusive, the results suggest that a case finding
      policy in postmenopausal osteoporosis would have a high cost/benefit ratio except
      for patients not responding to conventional therapies, or presenting borderline
      laboratory results.

PMID- 12200649
TI  - Hydroxyapatite/calcium carbonate (HA/CC) vs. plaster of Paris: a
      histomorphometric and radiographic study in a rabbit tibial defect model.
AB  - The search for an ideal bone substitute is ongoing. Multiple osteoconductive bone
      substitutes are available today. Plaster of Paris (POP) (calcium sulfate) has
      been used for more than 100 years for treatment of skeletal defects. This implant
      is compared to a new material, hydroxyapatite/calcium carbonate (HA/CC), in a
      rabbit tibia model. HA/CC is made from partial conversion of coralline calcium
      carbonate to hydroxyapatite and has an outer hydroxyapatite layer and an inner
      calcium carbonate core, a combination that leads to faster resorption than that
      of pure hydroxyapatite. This study compares the histomorphometric and
      radiographic properties of POP and HA/CC in a rabbit tibial defect. Both implants
      preferentially restore bone to the cortex relative to the canal. Plaster of Paris
      was fully resorbed by 6 weeks both radiographically and histometrically and HA/CC
      was substantially resorbed by 42 weeks. No significant difference was noted in
      volume fraction of bone between the two implants at 42 weeks postimplantation.
      Hydroxyapatite/calcium carbonate is a biocompatible bone graft substitute with a
      rate of resorption significantly slower than plaster of Paris.

PMID- 12200650
TI  - Fourier transform infrared microspectroscopic investigation of the organic and
      mineral constituents of peritubular dentin: a horse study.
AB  - Peritubular dentin (PTD) is a relatively dense mineralized tissue surrounding
      tooth dentin tubules, whose composition and mode of formation are still unclear.
      Fourier transform infrared microspectroscopic studies of the organic and mineral
      components of the highly developed horse PTD indicate that the peritubular matrix
      is less abundant than the intertubular matrix but is also mainly composed of
      collagen, which is more hydrated. These data suggest that most of the crystals
      are located outside the collagen fibrils and probably not associated with protein
      components. The crystals in PTD have nearly the same crystallinity as those in
      intertubular spaces, showing comparable amounts of carbonate ions, although some
      PO4 groups have different nonapatitic environments. Horse PTD composition is very
      similar to that of ITD, with collagen as the main protein component and
      carbonated apatite as the mineral fraction but the different proportions of these
      constituents and the greater water content in PTD suggest a different
      organization.

PMID- 12200651
TI  - Effects of collagen unwinding and cleavage on the mechanical integrity of the
      collagen network in bone.
AB  - The objective of this study was to investigate how molecular level changes in the
      collagen network affect its mechanical integrity. Our hypothesis is that the
      cleavage and unwinding of triple helices of collagen molecules significantly
      reduce the mechanical integrity of the collagen network in bone, whereas collagen
      crosslinks play a major role in sustaining the structural integrity of the
      collagen network. To test this hypothesis, the collagen molecular structure was
      altered in demineralized human cadaveric bone samples in the following two ways:
      heat induced unwinding and pancreas elastase induced cleavage of collagen
      molecules. Along with control specimens, the treated specimens were mechanically
      tested in tension to determine their strength, elastic modulus, toughness, and
      strain to failure. Also, the percentage of denatured collagen molecules and
      amounts of two major collagen crosslinks (hydroxylysylpyridinoline and
      lysylpyridinoline) were determined using high-performance liquid chromatography
      techniques. It was found that unwinding of collagen molecules may cause more
      reduction in stiffness (E) but less strain to failure (ef) than cleavage. Both
      collagen denaturation types cause similar changes in the strength (ss) and work
      to fracture (Wf) of the collagen network with no significant changes in
      hydroxylysylpyridinoline and lysylpyridinoline crosslinks. The results of this
      study indicate that the integrity of collagen molecules significantly affect the
      mechanical properties of the collagen network in bone, and that collagen
      crosslinks may play an important role in maintaining the mechanical integrity of
      the collagen network after collagen denaturation occurs.

PMID- 12200652
TI  - Regional bone loss after orthotopic liver transplantation in inbred rats: the
      role of hepatic denervation.
AB  - Bone loss and long-term persistence of osteoporosis with increased fracture risk
      are common after liver transplantation. It is unknown whether transplantation
      induced disruption of hepatic nerves, serving numerous regulatory metabolic and
      sensory functions, is herein involved. To test this possibility, we measured bone
      mineral density (BMD) by peripheral quantitative computed tomography (pQCT) and
      studied dynamic histomorphometry, radiocalcium kinetics, and biochemical
      parameters in 7 liver-transplanted and 7 sham-operated inbred rats. Although
      liver function was normal in TX rats, trabecular BMD of the first lumbar vertebra
      and total BMD of the femoral diaphysis were decreased by 13% and 6%,
      respectively, 9 months postsurgery. The breaking force of the femur was
      significantly lower by 21%. However, bone mass in the femoral and tibial
      metaphysis was preserved as evidenced by pQCT measurements and histomorphometry.
      Trabecular width and wall thickness were significantly decreased in vertebral
      cancellous bone, whereas indices of bone formation and resorption were normal or
      slightly reduced. Serum minerals, mineral balance, fractional and net absorption
      of Ca and Mg, serum calciotropic hormones, IGF-I, leptin, specific activity of
      45Ca in bone, 45Ca excretion, and biochemical indices of bone formation and bone
      resorption remained unchanged. We conclude that liver transplantation-related
      denervation causes cancellous and cortical bone loss in well-innervated bone
      sites such as the lumbar spine and the long bone diaphysis. Cancellous bone loss
      in TX rats is due to an impairment of osteoblast team performance and subsequent
      trabecular thinning. The mechanism uncovered by our study may contribute to long
      term bone loss after liver transplantation.

PMID- 12200654
TI  - Age-specific values and cutoff levels for the diagnosis of osteoporosis in
      quantitative ultrasound measurements at the calcaneus with SAHARA in healthy
      Japanese women: Japanese population-based osteoporosis (JPOS) study.
AB  - To establish the reference values of the quantitative ultrasound (QUS) indices in
      healthy Japanese women and to propose a diagnostic criterion for osteoporosis by
      means of the QUS indices, 659 healthy women aged 20-79 years recruited from a
      larger cohort study (JPOS study), were examined for bone mass measurements by QUS
      at the calcaneus (SAHARA, Hologic Inc., USA) and by dual-energy X-ray
      absorptiometry at the spine, hip, and distal forearm. We presented 10-year age
      specific mean values and T-scores of the QUS indices. The pattern of decrease in
      the T-score appeared to be linear in the QUS indices and total hip BMD but not in
      BMD at the spine. The T-score of the QUS of indices of the subjects in their 70s
      were significantly higher than that of BMD at the spine. The prevalence rates of
      osteoporosis in the subjects aged 50 and older diagnosed by QUS (8.7% for SOS,
      10.7% for BUA) were similar to that diagnosed by total hip BMD (11.5%) and
      significantly lower than that by the spine BMD (36.1%) when the WHO criteria were
      applied. We performed receiver-operating characteristic analysis to set a cutoff
      level of the QUS indices for the diagnosis of osteoporosis to accurately identify
      the subjects diagnosed by either the spine or total hip BMD. The highest
      likelihood ratios for SOS and BUA were obtained at the cutoff levels of 1,517.7
      m/sec (T-score: -1.58) with the sensitivity of 0.65 and the specificity of 0.65
      and 59.5 dB/MHz (T-score: -1.52) with 0.66 and 0.69, respectively. The diagnostic
      accuracy of QUS indices for osteoporosis was not superior to that of age.
      However, the QUS indices showed a significant contribution to forming the
      diagnosis of osteoporosis independently of age and body size in multivariate
      diagnostic models developed by the logistic regression analysis. Therefore, the
      cutoff values presented in this study may be used as a tentative criterion until
      the cutoff levels for the QUS indices are set according to the fracture risk.

PMID- 12200655
TI  - The effect of multiple pregnancies on lumbar bone mineral density in Japanese
      women.
AB  - OBJECTIVE: To elucidate the effect of multiple pregnancies on lumbar spine bone
      mineral density (BMD). METHODS: The BMD of the lumbar spines (L2-L4) of 1,113
      healthy women was measured within 7 days of childbirth. In addition 113 women had
      spine BMD measurements after their next delivery. RESULTS: In the cross-sectional
      study, there was no apparent effect of parity on lumbar BMD. In the longitudinal
      study, the mean BMD after the next delivery was significantly higher than that
      after the initial delivery (1.019 +/- 0.115 g/cm(2) vs. 1.006 +/- 0.117 g/cm(2),
      P = 0.001, paired t test) with a percent change (DeltaBMD%) of 1.4 +/- 4.2%.
      Multiple regression analysis to identify independent predictors of DeltaBMD%
      showed a negative correlation with maternal age at the subsequent delivery (P =
      0.033) but no correlation of DeltaBMD% with the length of lactation between the
      scans. CONCLUSION: Multiple pregnancies may not reduce maternal lumbar BMD,
      although the percentage decrease in BMD was greater in older women at the
      subsequent delivery. The length of lactation between the scans had no effect on
      these results.

PMID- 12200656
TI  - Uncoupling of bone turnover following hip replacement.
AB  - Studies using total hip replacement surgery as a model for acute hip injury have
      shown that bone mineral density of the proximal femur decreases 6-18% in the 6
      months following surgery. To examine the acute biochemical mechanism associated
      with bone loss, we measured two indicators of bone formation [serum osteocalcin
      (OC), serum bone-specific alkaline phosphatase (BSAP)], as well as two markers
      for bone resorption [urine and serum N-telopeptide cross-linked collagen type 1
      (NTx)], in 20 patients (10 men, 10 women, mean age 59.4 years) prior to hip
      replacement and 1-2 days postsurgery. The average OC value (ng/ml) decreased by
      57.3% following surgery (7.5 +/- 4.3 to 3.2 +/- 1.1, P <0.001), and the average
      BSAP level (U/L) decreased by 27.6% (19.9 +/- 5.6 to 14.4 +/- 3.7, P <0.001). In
      contrast, levels of urine NTx (nmol BCE/mmol Cr) did not change significantly
      after the surgery (73.9 +/- 47.2 to 70.1 +/- 29.7). In addition, there was no
      change in serum NTx (nmol BCE) after surgery (11.8 +/- 2.3 to 11.8 +/- 3.0). Six
      months after surgery, bone mass had not changed significantly from baseline.
      These findings suggest that there is an uncoupling of bone turnover following hip
      replacement surgery which is characterized by significant reductions in bone
      formation without compensatory decreases in bone resorption, potentially leading
      to bone loss. Longer periods of follow-up are needed to assess long-term bone
      mass changes.

PMID- 12200657
TI  - Maintenance of osteoblastic and adipocytic differentiation potential with age and
      osteoporosis in human marrow stromal cell cultures.
AB  - Osteoblasts and adipocytes share a common precursor cell in the bone marrow
      stroma, termed marrow stromal cell (MSC). As the volume of bone adipose tissue
      increases in vivo with age, we hypothesized that decreased bone formation
      observed during aging and in patients with osteoporosis (OP) is the result of
      enhanced adipogenesis and decreased osteoblastogenesis from the MSCs. Thus,
      cultures of MSCs were established from young donors (age 18-42, n = 34), elderly
      healthy donors (age 66-78, n = 20), and patients with OP (age 58-76, n = 15).
      Cells were cultured for 2 weeks in an adipogenic medium (containing 15% horse
      serum and 100 nM dexamethasone), osteogenic medium (containing 10% fetal calf
      serum [FCS] and 10 nM calcitriol), or control medium (10% FCS). The MSCs were
      identified by their abilities to form colonies. Total number of colonies,
      osteoblastic colonies stained positive for alkaline phosphatase (AP+), and
      adipocytic colonies containing adipocytes (Ad+) were quantitated. In addition,
      steady state mRNA levels of gene markers of adipocytic and osteoblastic
      phenotypes were determined using reverse-transcriptase polymerase chain reaction
      (RT-PCR). The adipogenic and osteogenic media induced cell differentiation and
      the expression of adipocytic and osteoblastic lineage-specific markers,
      respectively. We found no age-related changes in the osteoblastic or adipocytic
      colony formation or the steady state levels of mRNA of the adipogenic or
      osteogenic gene markers. Cells obtained from patients with OP showed a pattern of
      differentiation similar to those of age-matched controls. In conclusion, MSCs
      maintain their differentiation potential during aging and in patients with OP.
      Other mechanisms responsible for age-related decrease in bone formation need to
      be determined.

PMID- 12200658
TI  - Effects of human recombinant calcitonin on a rat osteopenia model induced by TPTX
      and arotinoid.
AB  - Recombinant human calcitonin (rh-CT) has been developed as an agent for patients
      with excessive bone resorption to replace calcitonins from animal species, which
      are associated with tolerance problems. In this study, inhibitory effects of rh
      CT against bone resorption were examined in thyroparathyroidectomized (TPTX)
      rats, the animal model of accelerated bone resorption induced by administering a
      synthetic retinoid (arotinoid). The arotinoid-treated TPTX rats exhibited signs
      of stimulated bone resorption, such as hypercalcemia, reduced bone mineral
      density, and inferior bone strength. Significant improvements were seen in all of
      these changes after a daily treatment with rh-CT (30, 300 U/kg s.c.) for 1 week.
      A histomorphometrical analysis showed that the treatment with rh-CT markedly
      suppressed the reduction of trabecular bone volume and that of cortical thickness
      in the femur of arotinoid-treated TPTX rats. These results suggest that rh-CT may
      prevent osteopenia caused by accelerated bone resorption.

PMID- 12200660
TI  - Laparoscopic duodenoduodenostomy for duodenal atresia.
AB  - A 3,220-g newborn baby with trisomy 21 presented with duodenal atresia. No other
      congenital malformations were diagnosed. Informed consent for a laparoscopic
      approach was obtained. The child was placed in a supine, head-up position
      slightly rotated to the left at the end of a shortened operating table. The
      surgeon stood at the bottom end with the cameraperson to his left and the scrub
      nurse to his right. The screen was at the right upper end. Open insertion of a
      cannula for a 5-mm 30 degrees telescope through the inferior umbilical fold was
      performed. A carbon dioxide (CO2) pneumoperitoneum with a pressure of 8 mmHg and
      a flow of 2l/min was established. Two 3.3-mm working cannulas were inserted; one
      in the left hypogastrium and one pararectally on the right at the umbilical
      level. Two more such cannulas were inserted; one under the xyphoid for a liver
      elevator and one in the right hypogastrium for a sucker. Mobilization of the
      dilated upper and collapsed lower duodenum was easy. After transverse enterotomy
      of the upper duodenum and longitudinal enterotomy of the distal duodenum, a
      diamond-shaped anastomosis with interrupted 5 zero Vicryl sutures were performed.
      The absence of air in the bowel beyond the atresia increased the working space
      and greatly facilitated the procedure. The technique proved to be easy, and the
      child did very well. Laparoscopic bowel anastomosis in newborn babies had not
      been described previously. Recently, a diamond-shaped duodenoduodenostomy for
      duodenal atresia was performed. The technique proved to be simple and is
      described in detail. The child did very well.

PMID- 12200661
TI  - Laparoscopic pancreas-preserving total gastrectomy for proximal gastric cancer. A
      case and technical report.
AB  - Although total gastrectomy with distal pancreatectomy has been the standard
      surgical treatment for advanced gastric cancer, this procedure is frequently
      complicated by leakage of pancreatic juice and postoperative diabetes mellitus.
      We present the case of a 74-year-old woman with proximal gastric cancer who
      underwent a laparoscopic modification of an open pancreas-preserving procedure
      first described by Maruyama et al. in 1995. With this novel technique, there is
      no pancreatic leakage, and at 12-month follow-up our patient remains free of
      diabetes. Herein we give the details of our new method and offer some caveats for
      its performance.

PMID- 12200662
TI  - Migration of endoclip into duodenum. A rare complication after laparoscopic
      cholecystectomy.
AB  - The long-term effect of spilled clips within the abdominal cavity after
      laparoscopic cholecystectomy is unknown. However, most surgeons agree that the
      migration of clips has limited clinical consequences. A few cases have been
      reported of clips that have migrated into the common bile duct, causing stone
      formation and/or obstructions. We present a case of gallstone pancreatitis
      treated with laparoscopic cholecystectomy that was complicated by bile leakage
      from the cystic duct stump 1 day after the procedure. Although the leaking stump
      sealed itself spontaneously after the placement of a biliary stent, a clip had
      migrated directly to the superior wall of the first portion of the duodenum.
      Herein the details of the patient's history are presented. We also discuss the
      possible mechanisms of clip migration and describe some preventive measures.

PMID- 12200663
TI  - Laparoscopic cholecystectomy and exploration of common bile duct in a patient
      with situs inversus.
AB  - Situs inversus is a rare anomaly with a genetic predisposition. We report a
      patient with situs inversus, cholelithiasis, and choledocholithiasis who was
      treated successfully with laparoscopic cholecystectomy and laparoscopic
      exploration of the common bile duct. We believe this to be the first such case
      reported in the literature.

PMID- 12200664
TI  - Vena cava injury. A serious complication during laparoscopic right adrenalectomy.
AB  - We report our experience with a case of vena cava injury during laparoscopic
      right adrenalectomy. A laparoscopic right adrenalectomy was performed in a 22
      year-old woman who suffered from a right surrenalian adenoma. Four trocars were
      used for the transperitoneal laparoscopic approach with the patient in the
      lateral decubitus position. After isolation of the medial margin of the gland and
      clipping and sectioning of the main adrenal vein, the right side of the vena cava
      was injured during dissection of the right upper pole, due to the use of
      monopolar scissors. The hemorrhage was managed immediately with the aid of
      fenestrated atraumatic forceps and an aspiration probe. A fifth trocar was
      inserted to evaluate the size of the lesion, which was then sutured
      laparoscopically with croised 5/0 nonresorbable stitches. No transfusion was
      needed. Operating time was 210 min. The post-operative course was uneventful.
      Hospital stay was 7 days. At 10-month follow-up, the patient had no problems
      related to the intraoperative complication. Our preliminary experience shows that
      the laparoscopic approach enables safer management of lesions involving large
      abdominal vessels. We believe that the transperitoneal approach is the
      preferential route for laparoscopic adrenalectomies. Monopolar coagulation can be
      dangerous and must be avoided when dissecting large vessels.

PMID- 12200665
TI  - Sigmoid volvulus after laparoscopic cholecystectomy. An unusual complication.
AB  - Laparoscopic cholecystectomy has become the standard surgical technique for
      treating symptomatic gallbladder disease. Intestinal obstruction after
      laparoscopic cholecystectomy is unusual. We present the case of a 37-year-old man
      who underwent routine laparoscopic cholecystectomy for cholelithiasis using an
      American four-port technique. He was well 24 h postoperatively and was
      discharged. He presented 36 h later with clinical features of bowel obstruction.
      A sigmoid loop was seen on a plain abdominal radiograph. Laparotomy revealed
      distension of the large and small bowel to the level of the rectosigmoid junction
      and a sigmoid volvulus. This was reduced by releasing adhesions to lengthen the
      sigmoid mesentery. A primary sigmoid resection and anastomosis was not attempted
      due to luminal discrepancy and lack of bowel preparation. The patient underwent
      interval sigmoid colectomy 2 weeks later. A sigmoid volvulus following
      laparoscopic cholecystectomy has not been previously reported. It may be related
      to the induction of the pneumoperitoneum, combined with the lateral tilt of the
      table and a long redundant sigmoid colon. This case expands the range of
      potential complications associated with laparoscopic cholecystectomy and
      illustrates the need for continued vigilance after apparently routine procedures.

PMID- 12200666
TI  - Early reduction of BCR-ABL mRNA transcript levels predicts cytogenetic response
      in chronic phase CML patients treated with imatinib after failure of interferon
      alpha.
AB  - The degree of tumor load reduction as measured by cytogenetic response is an
      important prognostic factor for chronic myelogenous leukemia (CML) patients on
      therapy. We sought to determine whether BCR-ABL transcript levels can predict
      chromosomal response. Residual disease was evaluated in 120 CML patients in
      chronic phase (CP) treated with the selective tyrosine kinase inhibitor imatinib
      after resistance or intolerance to interferon alpha (IFN). Median time of therapy
      was 401 days (range 111-704). BCR-ABL and total ABL transcripts were measured in
      486 peripheral blood (PB) specimens with a real time RT-PCR approach using
      fluorescent-labeled hybridization probes (LightCycler technology) and results
      were expressed as the ratio BCR-ABL/ABL. Cytogenetic response was determined in 3
      monthly intervals: From 101 evaluable patients, 42 achieved a complete (CR, 0%
      Philadelphia chromosome (Ph)- positive metaphases), 18 a partial (PR, 1-34% Ph+),
      13 a minor (MR, 35-94% Ph+), and 26 no response (NR, >94% Ph+). All PB samples
      were RT-PCR positive. The proportion of Ph+ metaphases and simultaneous BCR
      ABL/ABL ratios correlated with r = 0.74, P < 0.0001. In order to investigate
      whether early molecular analysis may predict cytogenetic response, quantitative
      RT-PCR data obtained after 1 and 2 months of therapy were compared with
      cytogenetic response at 6 months. BCR-ABL/ABL ratios after 1 month were not
      predictive, but results after 2 months correlated with the consecutive
      cytogenetic response (P = 0.0008). The probability for a major cytogenetic
      response was significantly higher in patients with a BCR-ABL/ABL ratio <20% after
      2 months of imatinib therapy. We conclude that: (1) quantitative determination of
      residual disease with real time RT-PCR is a reliable and sensitive method to
      monitor CML patients on imatinib therapy; (2) BCR-ABL/ABL ratios correlate well
      with cytogenetic response; (3) in IFN-pretreated patients all complete responders
      to imatinib have evidence of residual disease with the limited follow-up
      available; and (4) cytogenetic response at 6 months of therapy in CP patients is
      predictable with real time RT-PCR at 2 months.

PMID- 12200667
TI  - Effects of imatinib on bone marrow engraftment in syngeneic mice.
AB  - Chronic myeloid leukemia (CML) and a subset of acute lymphoblastic leukemias
      arise from the genetic reciprocal translocation t(9;22), forming the BCR-ABL
      fusion gene. These lead to the expression of the constitutively active tyrosine
      kinase BCR-ABL, which is the causative oncogene for these leukemias. Allogeneic
      bone marrow transplantation (BMT) or stem cell transplantation (SCT) is currently
      considered the only curative treatment for chronic myeloid leukemia (CML).
      Recently, the selective tyrosine kinase inhibitor imatinib mesylate (Glivec,
      formerly STI-571) has been shown to induce durable hematologic and major
      cytogenetic responses in a high percentage of patients with chronic phase CML. In
      patients with advanced disease remissions are transient and most patients relapse
      despite continued imatinib treatment. Some of these patients go on to receive
      allogeneic BMT or SCT, during which administration of imatinib is usually
      discontinued as it is believed to interfere with bone marrow engraftment. In this
      study, we examined the effect of imatinib on hematopoietic engraftment in a
      syngeneic mouse model. We found that imatinib has no significant influence on
      hematopoietic recovery in lethally irradiated mice in vivo. Thus, our results
      suggest that continued administration of imatinib in the course of BMT or SCT may
      be a feasible therapeutic regimen.

PMID- 12200668
TI  - Interleukin-3 protects Bcr-Abl-transformed hematopoietic progenitor cells from
      apoptosis induced by Bcr-Abl tyrosine kinase inhibitors.
AB  - Bcr-Abl tyrosine kinase has been validated as a molecular target for the
      treatment of chronic myelogenous leukemia (CML). More recently, it has been
      reported that CML patients could develop resistance to the Bcr-Abl tyrosine
      kinase inhibitor, imatinib (STI571, Gleevec), pointing to the need for
      development of additional Bcr-Abl tyrosine kinase inhibitors or other therapeutic
      strategies. It was also found that a significant proportion of patients who
      received the Bcr-Abl inhibitor did not achieve complete cytogenetic response.
      Mechanisms for incomplete cytogenetic response to Bcr-Abl inhibition are not
      entirely clear. We report here three new pyrido[2,3-d]pyrimidine Bcr-Abl tyrosine
      kinase inhibitors, PD164199, PD173952, PD173958, that induced apoptosis of Bcr
      Abl-dependent hematopoietic cells. An interleukin-3 (IL-3) autocrine loop was
      observed previously in primitive CD34(+)/Bcr-Abl(+) leukemic cells in CML
      patients. Using 32Dp210(Bcr-Abl)and Baf3p210(Bcr-Abl) cells as models, we tested
      whether IL-3 might protect Bcr-Abltransformed, IL-3-responsive cells from
      apoptosis caused by Bcr-Abl tyrosine kinase inhibition. Results of trypan blue
      exclusion, fluoroisothiocyanate-valyl-alanyl-aspartyl-[O-methyl] 
      fluoromethylketone (FITC-VAD-FMK), and Annexin-V/7-amino-actinomycin D (7-AAD)
      binding assays indicate that IL-3 could protect Bcr-Abl-transformed, IL-3
      responsive hematopoietic progenitor cells from apoptosis induced by Bcr-Abl
      tyrosine kinase inhibitors. This finding raises the possibility that the IL-3
      autocrine loop found in primitive CD34(+)/Bcr-Abl(+) cells in CML patients could
      contribute to the incomplete eradication of Bcr-Abl(+) cells by Bcr-Abl
      inhibition.

PMID- 12200669
TI  - Sphingosine 1-phosphate as a therapeutic agent.
AB  - The bioactive sphingolipid metabolite sphingosine-1-phosphate (S1P), formed by
      activation of sphingosine kinase in response to diverse stimuli, is an important
      lipid mediator that has novel dual actions - both inside and outside of cells.
      S1P is the ligand for a family of five G protein-coupled receptors. Activation of
      these GPCRs by S1P or dihydro-S1P regulates diverse processes, including cell
      migration, angiogenesis, vascular maturation, heart development, and neurite
      retraction. There is also abundant evidence that S1P can function as a second
      messenger important for regulation of calcium homeostasis, cell growth, and
      suppression of apoptosis. In many cases, the intracellular level of S1P and
      ceramide, another important sphingolipid metabolite associated with cell death
      and cell growth arrest, coordinately determine cell fate. Changes in S1P and
      ceramide have been implicated in a number of pathological conditions in which
      apoptosis plays an important role. Importantly, radiation-induced oocyte loss in
      adult female mice, the event that drives premature ovarian failure and
      infertility in female cancer patients, was completely prevented by in vivo
      therapy with S1P. Understanding the biosynthesis, metabolism and functions of S1P
      can uncover new targets for the pharmaceutical and therapeutic applications of
      S1P.

PMID- 12200670
TI  - CD34(+) or CD34(-): which is the more primitive?
AB  - Remarkable progress has been achieved in the characterization and isolation of
      primitive hematopoietic stem cells (HSC). HSC represent a very small subset of
      hematopoietic cells and provide self-renewal, possess differentiation capacity
      and allow a constant supply of the entire hematopoietic cell spectrum. Until
      recently, CD34 has been used as a convenient marker for HSC, since CD34(+) cells
      have been shown to possess colony-forming potential in short-term assays,
      maintain long-term colony-forming potential in in vitro cultures and allow the
      expression and differentiation of blood cells from different hematopoietic
      lineages in in vivo models. Clinical and experimental protocols have targeted
      CD34(+) cells enriched by a variety of selection models and have readily used
      these for transplantation, purging and gene therapies and targets for future
      organ replacement. Recent studies in murine and human models, however, have
      indicated that CD34(-) HSC exist as well, which possess engraftment potential and
      distinct HSC characteristics. These studies challenge the dogma that HSC are
      uniformly found in the CD34(+) subset, and question whether primitive HSC are
      CD34(+) or CD34(-). In this review, results on murine and human CD34(+) and CD34(
      ) HSC, differences between them and their possible interactions are examined.

PMID- 12200671
TI  - Clinical efficacy and antiangiogenic activity of thalidomide in myelofibrosis
      with myeloid metaplasia. A pilot study.
AB  - Increased neoangiogenesis has been reported in myelofibrosis with myeloid
      metaplasia (MMM). Thus we studied the effects of thalidomide, an antiangiogenic
      drug, in 12 MMM patients. Before treatment, all the cases showed a significantly
      increased micro-vessel density (MVD); in all eight tested cases bFGF and VEGF
      plasma levels were higher than controls. All patients presented disease
      progression in the last 3 months with standard therapy, regarding splenomegaly,
      anemia and/or thrombocytopenia and/or hyperleukocytosis. Thalidomide was
      administered at daily doses increasing from 100 to 600 mg. Eleven out of 12
      patients were evaluable. No progression of disease was seen during the treatment
      in any case. In particular, spleen size decreased in 7/11 patients, anemia
      improved in 3/4 (two are now transfusion independent), thrombocytopenia in 2/2
      and hyperleukocytosis in 2/5 patients. Side-effects were frequent, although not
      severe. After treatment, VEGF and bFGF plasma levels varied widely and in
      selected cases decreased. In particular, VEGF and/or bFGF decreased in 4/5
      responders and in 1/3 non-responders. Moreover, MVD significantly decreased in
      all the responders evaluated after treatment. We conclude that thalidomide is a
      feasible therapy in MMM patients and looks promising at least to control the
      growth progression of disease.

PMID- 12200672
TI  - Chemotherapy only compared to chemotherapy followed by transplantation in high
      risk myelodysplastic syndrome and secondary acute myeloid leukemia; two parallel
      studies adjusted for various prognostic factors.
AB  - Comparisons of the effectiveness of chemotherapy and transplantation in AML in
      first complete remission (CR) have focused almost exclusively on patients with de
      novo disease. Here we used Cox modelling to compare these strategies in patients
      with MDS and s-AML treated by the Leukemia Group of the EORTC or at the MD
      Anderson Cancer Center. All patients were aged 15-60. The 184 EORTC patients
      received conventional dose ara-C + idarubicin + etoposide for remission
      induction, and after one consolidation course, were scheduled to receive an
      allograft, or an autograft if a sibling donor was unavailable. The 215 MDA
      patients received various high-dose ara-C containing induction regimens, and in
      CR, continued to receive these regimens at reduced dose for 6-12 months. CR rates
      were 54% EORTC and 63% MDA (P = 0.09). Sixty-five of the 100 EORTC patients who
      entered CR received a transplant in first CR. Disease-free survival in patients
      achieving CR was superior in the EORTC cohort, the 4-years DFS rates were 28.9%
      (s.e. = 4.8%) EORTC vs 17.3% (s.e. = 3.7%) MDA (P = 0.017). Survival from CR was
      not significantly different in the EORTC and MDA groups, as was survival from
      start of treatment. After accounting for prognostic factors the conclusions were
      unchanged. Despite various problems with the analysis discussed below, the data
      suggest that neither transplantation nor chemotherapy, as currently practised,
      can be unequivocally recommended for these patients in first CR and that
      questions as to the superior modality may be less important than the need to
      improve results with both.

PMID- 12200673
TI  - Acute megakaryoblastic leukemia: experience of GIMEMA trials.
AB  - The objective of the study was to evaluate the incidence, characteristics,
      treatment and outcome of acute megakaryoblastic leukemia (AMeL) in patients
      enrolled in GIMEMA trials. Between 1982 and 1999, 3603 new consecutive cases of
      AML aged over 15 years were admitted to GIMEMA trials. Of them, 24 were AMeL. The
      incidence of AMeL among AML patients enrolled in GIMEMA trials was 0.6%
      (24/3603). Diagnosis was based on morphological criteria. Out of 11 cytogenetic
      studies performed two presented chromosome 3 abnormalities. Twelve patients (50%)
      reached a CR, five (21%) died in induction and seven (27%) were unresponsive. The
      median duration of CR was 35 weeks (range 10-441). Seven patients underwent
      transplantation procedures (1 BMT, 4 aBMT, 2 aPBSCT). Four patients died in CR
      due to chemotherapy-related complications. Comparing the CR rate between AMeL and
      the other cases of AML enrolled in GIMEMA trials, no differences were observed.
      These results were mirrored for different age groups. The median survival was 40
      weeks. At present, after a follow-up of a minimum of 2 years, only two patients
      are alive in CR, all the others having died. A 5-year Kaplan-Meier curve shows a
      disease-free survival of 17% and an actuarial overall survival of 10%. AMeL is a
      rare form of AML. The CR duration and the overall survival in this group of
      patients are very poor, even if similar to those observed in other AML.
      Furthermore, a high number of deaths in CR were observed. On the basis of these
      data, a specific therapeutic approach, possibly with innovative treatments,
      should be evaluated.

PMID- 12200674
TI  - Antibody-targeted chemotherapy of older patients with acute myeloid leukemia in
      first relapse using Mylotarg (gemtuzumab ozogamicin).
AB  - We analyzed the safety and efficacy of Mylotarg (gemtuzumab ozogamicin, an
      antibody-targeted chemotherapy consisting of a humanized anti-CD33 antibody
      linked to calicheamicin, a potent antitumor antibiotic) in the treatment of 101
      patients > or =60 years of age with acute myeloid leukemia (AML) in untreated
      first relapse in three open-label trials. Mylotarg is administered as a 2-h
      intravenous infusion at 9 mg/m(2) for two doses with 14 days between doses. The
      overall remission rate was 28%, with complete remission (CR) in 13% of patients
      and complete remission with incomplete platelet recovery (CRp) in 15%. Median
      survival was 5.4 months for all patients and 14.5 months and 11.8 months for
      patients achieving CR and CRp, respectively. CD33 antigen is present on normal
      hematopoietic progenitor cells; thus, an expected high incidence of grade 3 or 4
      neutropenia (99%) and thrombocytopenia (99%) was observed. The incidences of
      grade 3 or 4 elevations of bilirubin and hepatic transaminases were 24% and 15%,
      respectively. There was a low incidence of grade 3 or 4 mucositis (4%) and
      infections (27%) and no treatment-related cardiotoxicity, cerebellar toxicity, or
      alopecia. Mylotarg is an effective treatment for older patients with CD33
      positive AML in first relapse and has acceptable toxicity.

PMID- 12200675
TI  - Gene transfer of CD154 and IL12 cDNA induces an anti-leukemic immunity in a
      murine model of acute leukemia.
AB  - IL12 is an essential cytokine for the generation of T helper 1 response, natural
      killer (NK) cells and cytotoxic T lymphocyte (CTL) stimulation. CD154 triggers
      CD40 on antigen-presenting cells, thus inducing antigen presentation to the
      immune system and production of IL12. As IL12 and CD154 share several pathways
      mediating immune response, we investigated in an aggressive murine model of acute
      leukemia the relative antileukemic efficiency of IL12, CD154 and IL12 + CD154
      gene transfer. Live leukemic cells transduced by IL12, CD154, and IL12 + CD154
      showed reduced leukemogenicity but CD154 protective effect was reduced when 10(6)
      leukemic cells were injected. Vaccines with lethally irradiated IL12-transduced
      cells were able to cure mice previously injected with 10(4) leukemic cells and
      adoptive transfer of IL12-induced antileukemic immunity protected recipient mice.
      NK cytotoxicity was enhanced in mice vaccinated with leukemic cells transduced by
      IL12, CD154, and CD154 + IL12. IL12 transduced cells induced IFN-gamma mRNA in
      CD4(+) and CD8(+) T cells isolated from the spleen of vaccinated animals,
      however, in vivo depletion experiments showed that IL12 vaccine effect was CD4(+)
      but not CD8(+) T cell dependent. We conclude that IL12 gene is a more potent
      candidate than CD154 for gene therapy of acute leukemia.

PMID- 12200676
TI  - Transduction of acute myeloid leukemia cells with third generation self
      inactivating lentiviral vectors expressing CD80 and GM-CSF: effects on
      proliferation, differentiation, and stimulation of allogeneic and autologous anti
      leukemia immune responses.
AB  - Acute myeloid leukemia (AML) patients treated with available therapies achieve
      remission in approximately 60% of cases, but the long-term event-free survival is
      less than 30%. Use of immunotherapy during remission is a potential approach to
      increase survival. We propose to develop cell vaccines by genetic modification of
      AML cells with CD80, an essential T cell costimulator that is lacking in the
      majority of AML cases, and GM-CSF, to induce proliferation and activation of
      professional antigen-presenting cells. Here, we evaluated third generation self
      inactivating (SIN) lentiviral vectors, which have the potential advantage of
      improved safety. CD80 and GM-CSF expression by these vectors was higher than that
      reported with second generation vectors (Stripecke et al, Blood 2000; 96: 1317
      1326). In some cases, endogenous GM-CSF expression by transduced AML cells
      induced phenotypic changes consistent with the maturation of leukemia blasts into
      antigen-presenting cells. Further, in all cases studied, GM-CSF expression was
      associated with higher proliferation and cell viability. Allogeneic and
      autologous mixed lymphocyte reactions performed with transduced irradiated AML
      cells expressing CD80 and/or GM-CSF demonstrated that expression of either
      transgene enhanced T cell activation. These pre-clinical data demonstrate the
      potential feasibility of third generation SIN vectors for use in AML
      immunotherapy.

PMID- 12200677
TI  - Persisting multilineage transgene expression in the clonal progeny of a
      hematopoietic stem cell.
AB  - Many applications of hematopoietic gene therapy require selection for clones with
      active transgene expression. However, it was unclear whether the clonal progeny
      of a retrovirally transduced hematopoietic stem cell would be capable of
      maintaining transgene expression through serial repopulation and multilineage
      differentiation. Such investigations require simultaneous analyses of clonality,
      multilineage activity and transgene copy numbers. Using a mouse model, the
      present study demonstrates that a single hematopoietic stem cell expressing a
      marker gene from one or two insertions of a simple retroviral vector actively
      maintains multilineage transgene expression in the vast majority (80-99%) of bone
      marrow and peripheral blood cells. Gene expression persisted through serial
      transplantations for at least 97 weeks post gene transfer and was observed in the
      lymphoid (B, T and NK cells), myeloid (CD11b(+), Gr-1(+)), erythroid (Ter119(+),
      mature red blood cells) and megakaryocytic (as indicated by platelets) progeny.
      Therefore, a single immunoselection for hematopoietic stem cells expressing the
      transgene in vivo was sufficient to establish a completely chimeric
      hematopoiesis. These observations imply that the retroviral vectors used in this
      study contain cis-elements that mediate expression through massive clonal
      expansion and multilineage differentiation, provided the insertion occurred in
      genetic loci permissive for expression in hematopoietic stem cells.

PMID- 12200678
TI  - Farnesyl transferase inhibitor R115777 induces apoptosis of human myeloma cells.
AB  - R115777, a nonpeptidomimetic farnesyl transferase inhibitor has recently
      demonstrated a significant antileukemic activity in vivo in acute myeloid
      leukemia. Multiple myeloma (MM) is a fatal hematological malignancy characterized
      by an accumulation of long-lived plasma cells within the bone marrow. In the
      present study, we have investigated the effect of the R115777 on growth and
      survival of myeloma cells. We have found that R115777 induced (1) a significant
      and dose-dependent growth inhibition of the three myeloma cell lines tested; and
      (2) a significant and time-dependent apoptosis. R115777 also induced apoptosis in
      the bone marrow mononuclear cell population of four MM patients, being almost
      restricted to the malignant plasma cells. Finally, we have investigated the
      effect of the R115777 in the Ras/MAPK and JAK/STAT pathways which are implicated
      in survival and/or proliferation in MM. The phosphorylation of both STAT3 and
      ERK1/2 induced by IL-6 was totally blocked at 15 microM of R115777 and partially
      blocked when R115777 was used at 10 and 5 microM. The induction of apoptosis by
      R115777 in myeloma cells and its implication in the regulation of JAK/STAT
      signalling suggest that R115777 might be an interesting therapeutical approach in
      MM.

PMID- 12200679
TI  - Minimal residual disease (MRD) status prior to allogeneic stem cell
      transplantation is a powerful predictor for post-transplant outcome in children
      with ALL.
AB  - We have retrospectively investigated the relationship between the level of
      minimal residual disease (MRD) detected in bone marrow taken prior to
      conditioning therapy and outcome following stem cell transplantation for high
      risk childhood ALL. Forty-one patients, in whom both a molecular marker of MRD
      and sufficient archival material was available, were included in the study. All
      were in remission at BMT: eight in CR1, 32 in CR2 and five in greater than CR2.
      MRD was measured by PCR amplification of antigen receptor gene rearrangements and
      clone-specific oligoprobing, the median sensitivity of detection being one
      leukaemic cell in 10000 normals. Results were classified as high-level positive
      (if a clonal band was evident after electrophoresis), low-level positive (if MRD
      was detected only after oligoprobing) and negative. MRD was detected at high
      levels in 17 patients, at low levels in 10 patients and 14 patients were MRD
      negative at the time of transplant. The 5-year event-free survival for these
      groups was 23%, 48% and 78%, respectively (P = 0.022). Limited multivariate
      analysis confirmed the significance of MRD (P = 0.0095) vs CR status, donor type,
      sex, immunophenotype and acute GvHD. This study confirms the strong relationship
      between MRD level and outcome following allogeneic transplantation. In contrast
      to a previous study we observed that a minority of children with high-level pre
      BMT MRD can enter long lasting remission. The possible role for acute GVHD
      coupled with a graft-versus-leukaemia effect in the clearance of high level MRD
      in patients with ALL is discussed.

PMID- 12200680
TI  - Therapy-related myelodysplastic syndrome after autologous stem cell
      transplantation for breast cancer.
AB  - Therapy-related myelodysplastic syndrome and acute myelogenous leukemia (t
      MDS/AML) are serious complications of chemotherapy and radiotherapy for cancer.
      High-dose chemotherapy followed by autologous stem cell transplantation (ASCT)
      may be associated with an increased incidence of these complications. The
      frequency of t-MDS/AML after ASCT for breast cancer is uncertain. We reviewed our
      database of 379 consecutive breast cancer ASCT patients treated with alkylator
      based chemotherapy, followed for a median of 1.52 years (range 0-8.97), with a
      median survival of 6.16 years. Three patients have developed tMDS/AML. The
      probability of developing this complication at 5 years is 0.032 in our series. We
      have used pathologic, cytogenetic and molecular methods to evaluate which
      portions of therapy may have predisposed to the development of this complication.
      Cytogenetic abnormalities were not found in the stem cell harvests of these
      patients by metaphase analysis or by fluorescence in situ hybridization (FISH).
      One patient demonstrated a clonal X chromosome inactivation pattern in her stem
      cell harvest, indicating pre-transplant chemotherapy may have been responsible
      for the development of her leukemia. As two of our patients developed this
      complication at greater than 4 years post-transplant, the number of cases may
      increase with longer follow-up. While the incidence appears to be low, further
      prospective and retrospective analysis will be necessary to determine which
      portions of therapy predispose to the development of t-MDS/AML in patients
      undergoing ASCT for treatment of breast cancer.

PMID- 12200681
TI  - Correlation of bone marrow angiogenesis and mast cells with tryptase activity in
      myelodysplastic syndromes.
AB  - Bone marrow samples from 30 patients with myelodysplastic syndromes (MDS) grouped
      according to the International Prognostic Scoring System for MDS were
      investigated for counts of microvessels, total metachromatic mast cells (MC) and
      MC expressing tryptase, an angiogenesis-inducing molecule. Counts were higher in
      patients with a poor prognosis. The observation of a high correlation between
      microvessel counts and both total metachromatic and tryptase-reactive MC in all
      samples suggests that angiogenesis in MDS increases with their progression and
      that MC may intervene in the angiogenic response in MDS through tryptase
      contained in their secretory granules.

PMID- 12200682
TI  - Infant acute lymphoblastic leukemia - combined cytogenetic, immunophenotypical
      and molecular analysis of 77 cases.
AB  - We used karyotyping, fluorescence in situ hybridization (FISH), Southern
      blotting, and RT-PCR in order to analyze prospectively 77 infants (less than 1
      year of age) with acute lymphoblastic leukemia for the occurrence of 11q23/MLL
      rearrangements and/or other cytogenetic abnormalities. Out of the 69 informative
      samples we found an 11q23/MLL rearrangement in 42 cases (61%). Regarding only pro
      B ALL cases, the incidence of 11q23/MLL rearranged cases, however, reached more
      than 90% The infants were treated within the therapy studies ALL-BFM90, ALL-BFM95
      and CoALL-05-92. For patients with an adequate follow-up of 4 years the event
      free survival of the 11q23/MLL-positive and 11q23/MLL-negative group was 0.2 or
      0.64, respectively (P = 0.024). The monoclonal antibody 7.1. (moab 7.1) does not
      react with normal hematopoetic precursors or mature blood cells but was shown to
      specifically react with leukemic cells bearing a rearrangement of chromosome
      11q23 or the MLL gene, respectively. We, therefore, specifically addressed the
      question whether the reactivity of moab 7.1, as determined by flow cytometry, may
      substitute for molecular testing of an 11q23/MLL rearrangement in this cohort of
      infant ALLs. Reactivity of moab 7.1 indicated a 11q23/MLL rearrangement with a
      specificity of 100%. However, five of the 11q23/MLL-positive cases did not react
      with moab 7.1 indicating a sensitivity of 84% only. Three of these five moab 7.1
      negative but 11q23/MLL-positive cases could be identified by their unique
      expression pattern of CD65s and/or CD15. Thus, 95% of all 11q23/MLL-positive ALL
      cases in infancy may be identified by flow cytometry based on their expression of
      CD15, CD65s and/or moab 7.1.

PMID- 12200683
TI  - Surface membrane antigen expression changes induced in vitro by exogenous growth
      factors in chronic lymphocytic leukemia cells.
AB  - The factors determining the growth and survival of cells in B chronic lymphocytic
      leukemia (CLL) have remained poorly understood. We investigated the effects of
      optimal mitogen combinations (OMCs) on the expression of 26 surface membrane
      antigens among 33 CLL patients. The seven OMCs used were selected after pre
      testing 14 combinations of (1) S. aureus Cowan I (SAC), (2) interleukin-2 (IL-2),
      (3) tumor necrosis factor alpha (TNF-alpha) and (4) 12-O-tetradecanoylphorbol 13
      acetate (TPA; also known as phorbol 12-myristate 13-acetate or PMA). In flow
      cytometry we revealed that OMCs induced statistically highly significant
      upregulation of the expression of CD5, CD11c, CD19, CD22, CD23, CD25, CD38, CD40,
      CD45, CD45RO, CD95, CD126, CD130 and FMC7, and downregulation of CD20 and CD124
      expression. Interestingly, the expression of CD27, CD45RA, CD79b, CD80, CD122 and
      that of the immunoglobulin gene superfamily members CD21, Ig-kappa, Ig-lambda, Ig
      delta and Ig-micro were not significantly affected under similar conditions. The
      expression of several antigens was co-regulated, suggesting common regulatory
      pathways. These antigens include CD11c/CD5, CD11c/CD22, CD11c/CD126, CD11c/FMC7
      as well as CD27/CD45, CD27/CD45RA and CD27/CD79b. Upregulation of surface antigen
      expression, induced by OMCs, should be applicable in antibody therapy in vitro
      and in vivo, and in negative stem cell selection for autotransplantation.
      Furthermore, the current strategy to enhance cell surface antigen expression may
      be a versatile tool to raise humoral and cell-mediated host defense against CLL
      cells. Upregulation of proteins mediating positive growth signals (eg CD25, CD40)
      and negative signals or apoptosis (eg CD95) may be used to sensitize cells to
      chemotherapy and programmed cell death.

PMID- 12200684
TI  - Prognostic significance of FLT3 internal tandem repeat in patients with de novo
      acute myeloid leukemia treated with reinforced courses of chemotherapy.
AB  - FLT3 internal tandem duplications (FLT3-ITDs) are present in nearly 25% of
      patients with AML and have been associated with poor response to conventional
      therapy and poor outcome. We retrospectively evaluated the effect of reinforced
      courses of chemotherapy on the prognostic value of FLT3-ITDs in 159 AML patients
      prospectively enrolled in the ALFA-9000 trial, which randomly compared three
      reinforced induction regimens (standard 3+7 including high-dose daunorubicin,
      double induction, and timed-sequential therapy). FLT3-ITD was present in 40/159
      (25%) blast samples and associated with high WBC (P = 0.002) and cytogenetics (P
      < 0.001) with a higher incidence (35%) in patients with a normal karyotype. There
      was no difference in CR rate between FLT3-wt and FLT3-ITD patients (80% vs 78%).
      Relapse-free survival (RFS) was similar in both groups (5-year RFS, 33% vs 32%; P
      = 0.41), even after adjustment for age, sex, WBC, cytogenetics, and treatment
      arm. A trend to a worse survival was observed in the FLT3-ITD group (estimated 5
      year OS, 23% vs 37%; P = 0.09), mainly in patients with a normal karyotype. This
      was associated with a dramatic outcome in relapsing FLT3-ITD patients (estimated
      3-year post-relapse survival, 0% vs 27%; P = 0.04). These results suggest that
      the bad prognosis associated with FLT3-ITDs in AML might be partly overcome using
      reinforced chemotherapy. Early detection of FLT3 mutations might thus be useful
      to intensify induction as well as post-remission therapy in FLT3-ITD patients.

PMID- 12200685
TI  - Exposure to low concentrations of etoposide reduces the apoptotic capability of
      leukaemic cell lines.
AB  - The use of topoisomerase inhibitors has been associated with the development of
      secondary malignancies, suggesting that these agents can induce DNA damage that
      may be persistent. We have investigated the effect of short exposures (>3 days)
      to low etoposide concentrations (LC-etoposide, 0.01-0.04 microM) on the ability
      of leukaemic cells to initiate apoptosis. Results showed that although LC
      etoposide had no effect on cell growth characteristics, the pre-culture of cells
      with LC-etoposide conferred resistance to subsequent exposure to cytotoxic
      concentrations of etoposide (0.3 microM etoposide in HL60 on day 3: %V: 95.2 +/-
      1.6% vs 60.3 +/- 12.1% in control cells with no pre-culture, and %A: 5.1 +/- 0.2
      vs 19.0 +/- 0.7%; P < 0.001). This effect was still observed 4 weeks after the
      initial drug exposure. Associated with these observations was a three-fold
      increase in genetic instability and a reduction in induced bax protein levels.
      The anti-cytotoxic effect was also shown to be specific to topoisomerase II (topo
      II) inhibitors, as the pre-culture of cells with a low doxorubicin concentration
      also induced resistance, while low cisplatin concentrations did not. The
      persistence of these alterations in cellular processes following an initial
      exposure to topo II inhibitors suggests a DNA-based mechanism, and highlights the
      existence of drug/target interactions even at very low drug concentrations.

PMID- 12200686
TI  - Stromal cells prevent apoptosis of AML cells by up-regulation of anti-apoptotic
      proteins.
AB  - The aim of this study was to study interactions between stromal bone marrow
      microenvironment and leukemic cells. We tested the hypothesis that stromal cells
      prevent apoptosis of AML cells by up-regulating anti-apoptotic proteins in
      leukemic blasts. In HL-60 and NB-4 cells, serum deprivation- and ara-C-induced
      apoptosis was diminished when cells were cocultured with murine MS-5 stromal
      cells (P < 0.02). This effect was reproduced with conditioned medium from MS-5
      cells. Cocultivation with stromal cells induced Bcl-2 expression levels, both by
      PCR analysis and flow cytometry. In primary AML (n = 14), ara-C-induced apoptosis
      was significantly lower in cells cocultured with MS-5 cells than in controls (P <
      0.001). This effect was partially preserved when leukemic cells were separated
      from stromal cells by a microporous insert (in 5/9 samples, P = 0.04). In
      addition, Bcl-2 levels were significantly higher in stroma-supported than in
      control CD34(+) AML cells (P < 0.01). Bcl-X(L) levels were higher in 5/7 samples
      grown on stromal layers. Of note, in AML patients resistant to induction
      chemotherapy (n = 6), Bcl-2 increased significantly after cultivation with
      stromal cells, but no such increase was noted in cells from chemotherapy
      sensitive patients. In conclusion, MS-5 stromal cells prevented apoptosis in HL
      60 cells and in primary AML blasts via modulation of Bcl-2 family proteins. The
      observed association of high Bcl-2 expression in stroma-supported AML blasts in
      vitro with resistance to chemotherapy in vivo suggests that the same mechanisms
      may be operational in vivo.

PMID- 12200687
TI  - High Bcr-Abl expression prevents the translocation of Bax and Bad to the
      mitochondrion.
AB  - Bcr-Abl is a constitutively active tyrosine kinase involved in the development
      and progression of chronic myeloid leukaemia (CML). It has been demonstrated that
      Bcr-Abl-positive cells can be uniquely resistant to apoptosis induced by
      different types of stimuli, but the mechanism by which this is achieved is not
      defined. In this study we have investigated how cells expressing high expression
      levels of Bcr-Abl may gain resistance to cytotoxic drugs. We have established
      cell lines expressing low and high expression levels of Bcr-Abl. Cells expressing
      elevated Bcr-Abl are resistant to cytotoxic drugs. In drug-sensitive 32D-parental
      and low Bcr-Abl expressing cells, pro-apoptotic Bcl-2 family members, Bax and Bad
      translocate from the cytosol to the mitochondrion following a cytotoxic insult.
      In contrast, high Bcr-Abl expression prevents the early translocation of these
      pro-apoptotic proteins to the mitochondrion, mitochondrial membrane potential is
      retained and caspases are inactive. We also demonstrate that IL-3 can contribute
      to drug resistance in low Bcr-Abl expressing cells, however, independent
      inhibition of IL-3 activated pathways (PI3K/AKT and Jak/STAT) does not sensitise
      cells to apoptosis. This study demonstrates that the subcellular translocation of
      Bax and Bad can be regulated by elevated Bcr-Abl expression and this may be a key
      event in the abrogation of an apoptotic response following a cytotoxic insult.

PMID- 12200688
TI  - CD20-induced B cell death can bypass mitochondria and caspase activation.
AB  - The apoptotic pathway activated by chimeric anti-CD20 monoclonal antibodies
      (rituximab, IDEC.C2B8) was analyzed using the Burkitt lymphoma cell line Ramos.
      Crosslinking of CD20 (CD20XL) induced apoptosis in Ramos cells, which involved
      loss of mitochondrial membrane potential (Deltapsi(m)), the release of cytochrome
      c (cyt-c), and activation of caspases-9 and -3. Nevertheless, several lines of
      evidence showed that the apoptotic outcome did not depend on these events. First,
      under circumstances where Ramos cells display resistance to either CD95- or B
      cell receptor (BCR)-induced apoptosis, CD20XL-induced apoptosis was not affected,
      pointing to a distinct pathway. Second, the broad-spectrum caspase inhibitor zVAD
      fmk prevented processing of caspase-9, -3 and PARP as well as DNA fragmentation,
      but did not block apoptosis as measured by annexin V staining, cell size and
      membrane integrity. Lastly, Bcl-2 overexpression blocked cyt-c release and the
      decrease in Deltapsi(m), and completely prevented CD95- or BCR-mediated
      apoptosis; however, it did not affect CD20XL-induced cell death. We conclude that
      although CD20XL can initiate the mitochondrial apoptosis pathway, CD20-induced
      apoptosis does not necessarily require active caspases and cannot be blocked by
      Bcl-2. Since most chemotherapeutic drugs require the activation of caspases to
      exert their cytotoxicity, these findings provide an important rationale for the
      use of CD20 mAbs in chemoresistant malignancies.

PMID- 12200689
TI  - Incidence and significance of cryptic chromosome aberrations detected by
      fluorescence in situ hybridization in acute myeloid leukemia with normal
      karyotype.
AB  - To better define the incidence and significance of cryptic chromosome lesions in
      acute myeloid leukemia (AML), fluorescence in situ hybridization (FISH) studies
      were performed in interphase cells and, when appropriate, in metaphase cells and
      in morphologically intact BM smears. Fifty-five adult de novo AML (group A) and
      27 elderly AML or AML after myelodysplastic syndrome (AML-MDS) (group B) were
      tested using probes detecting the following anomalies: -5, -7, +8, deletions of
      5q31, 7q31, 12p13/ETV6, 17p13/p53, 20q11. All the patients had a normal karyotype
      in more than 20 cells and tested negative for the common AML-associated fusion
      genes. No patient in group A was found to carry occult chromosome anomalies,
      whereas 8/27 patients in group B (P < 0.0001) showed 5q31 or 7q31 deletion (three
      cases each), a 17p13/p53deletion or trisomy 8 (one case each) in 33-60%
      interphase cells. Metaphase cells showed only one hybridization signal at 5q31
      (three cases) and 7q31 (one case), whereas two normal signals at 7q31 and
      chromosome 8 centromeres were seen in two patients with 7q deletion and trisomy 8
      in interphase cells. The majority of blast cells (76-94%) carried the chromosome
      anomaly in all cases; erythroid involvement in a minority of cells was seen in
      three patients. In group B, the presence of occult chromosome anomalies was
      associated with exposure to myelotoxic agents in the workplace (5/8 cases vs
      3/19, P = 0.026) and with a lower complete remission rate (0/6 patients vs 7/12,
      P = 0.024). We arrived at the following conclusions: (1) cryptic chromosome
      deletions in the order of a few hundred kb magnitude may be found in a fraction
      of elderly AML or MDS-related AML and not in de novo adult AML with normal
      karyotype; (2) these chromosome lesions are usually represented by submicroscopic
      rearrangements; (3) they display a specific pattern of cell-lineage involvement
      arguing in favor of their role in the outgrowth of the leukemic blast cells; (4)
      they are associated with a history of exposure to myelotoxic agents in the
      workplace and, possibly, with resistance to induction treatment.

PMID- 12200690
TI  - Large deletions 5' to the ETO breakpoint are recurrent events in patients with
      t(8;21) acute myeloid leukemia.
AB  - Recurrent chromosomal rearrangements are observed in many leukemia subtypes.
      Recently, it has been shown that several of these translocations/inversions were
      associated with the loss of sequences located in the vicinity of the chromosomal
      breakpoints. So far, such deletions have not been described for the t(8;21)
      translocation. We have analyzed a series of 65 patients with t(8;21) using
      several probes specific for the ETO and AML1 regions. We have found six patients
      (9%) with deletion of the region 5' to ETO. In all six patients, the deletion
      encompassed at least 260 kb, and was even larger in two patients (up to 2 Mb). A
      similar analysis of the 21q22 region did not reveal any deletion of the 3'AML1
      region. In conclusion, cytogenetically undetectable small deletions located
      immediately 5' to the ETO breakpoint were found to accompany the t(8;21)
      translocation in a significant percentage of cases. The clinical significance, if
      any, of these deletions remains to be determined.

PMID- 12200692
TI  - Retinoic acid receptor antagonism in vivo expands the numbers of precursor cells
      during granulopoiesis.
AB  - The role/s of retinoids in granulopoiesis has been recognised for many years,
      being powerful differentiation inducers. The physiological role/s of retinoic
      acid receptor (RAR)-mediated signalling during adult haemopoiesis has by contrast
      proved more elusive. The recent generation of highly specific pan-RAR antagonists
      has now made possible an assessment of the specific physiological role/s of RAR
      signalling, allowing the separation for the first time of the RAR and RXR
      pathways. Mice were treated with AGN194310, a synthetic retinoid that antagonises
      the physiological function of the three RAR isotypes (alpha, beta, gamma) but
      does not interact with RXRs. Analyses of the granulocytic lineage using Gr-1, c
      Kit and CD11b antibodies, demonstrated that granulocyte numbers were strikingly
      increased across haemopoietic compartments in all AGN194310-treated mice. A
      significant increase in the frequency of progenitor cells containing granulocytes
      was observed in the bone marrow of mice following treatment with AGN194310. In
      contrast we were not able to detect any differences in cell death of either
      mature granulocytes or granulocytic progenitors from AGN194310-treated mice
      compared with control animals. These data demonstrate an essential role for RAR
      signalling in regulating the numbers of granulocytic precursors in vivo.

PMID- 12200691
TI  - The human promyelocytic leukemia zinc finger gene is regulated by the Evi-1
      oncoprotein and a novel guanine-rich site binding protein.
AB  - PLZF (promyelocytic leukemia zinc finger ) is a transcription factor disrupted in
      t(11;17)-associated acute promyelocytic leukemia which is highly expressed in
      undifferentiated myeloid cells. To address the tissue-specific regulation of the
      promoter, we isolated sequences 1.2-kb 5' to the transcriptional start site.
      Sequence analysis demonstrated that this region contains one TATA box and several
      putative transcription factor binding sites including four G/C-rich sites and one
      Evi-1-like site. A fragment of the promoter spanning 158-bp upstream of the
      transcription start site displayed relative specificity for PLZF-expressing
      myeloid cells. Functional promoter assays revealed that an Evi-1-like site at 
      140/-130 was essential for full promoter activity in every cell line tested while
      a G-rich site at -15/-7 was important for tissue specificity. Electrophoretic
      mobility shift assays showed that Evi-1 binds specifically to -140/-130 Evi-1
      like site and overexpression of Evi-1 in K562 cells activated the PLZF promoter.
      UV cross-linking assays showed that the proximal, tissue specific element at -15/
      7 bound a novel 28 kDa protein. These results indicate as with other myeloid
      genes, a relatively small segment of DNA can direct tissue-specific expression,
      but unlike other myeloid promoters, no critical PU.1 or C/EBP sites were found.

PMID- 12200693
TI  - Nuclear factor-erythroid 2 (NF-E2) expression in normal and malignant
      megakaryocytopoiesis.
AB  - Although the transcription factor nuclear factor-erythroid 2 (NF-E2) is known to
      be functionally linked to the megakaryocytic lineage, little is known about its
      role in malignant megakaryocytes. We used real-time RT-PCR and Western blotting
      to investigate expression of NF-E2 and its partner, MafG, in CD34-derived normal
      (five cases) and malignant megakaryocytes from essential thrombocythemia (ET)
      patients (eight cases) and in megakaryoblastic cell lines. We also quantitated
      the mRNA of the thromboxane synthase (TXS) gene, which is directly regulated by
      NF-E2. Although real-time RT-PCR showed that both a and f NF-E2 isoforms were
      significantly reduced with respect to the normal counterpart both in ET
      megakaryocytes and in cell lines (P < or = 0.01), western blotting revealed
      decreased NF-E2 protein expression only in the latter. However, both the NF
      E2a/MafG mRNA ratio (P < or = 0.01) and TXS (P< or = 0.01) mRNA expression were
      significantly reduced in megakaryocytes from ET patients and cell lines with
      respect to healthy subjects. These two findings provide strong indirect evidence
      of altered activity of the a isoform of NF-E2 in malignant megakaryocytes,
      raising the possibility that NF-E2 could play a role in megakaryocyte
      transformation.

PMID- 12200694
TI  - Stromal cells from murine embryonic aorta-gonad-mesonephros region, liver and gut
      mesentery expand human umbilical cord blood-derived CAFC(week6) in extended long
      term cultures.
AB  - The first definitive long-term repopulating hematopoietic stem cells (HSCs)
      emerge from and undergo rapid expansion in the embryonic aorta-gonad-mesonephros
      (AGM) region. To investigate the presumptive unique characteristics of the
      embryonic hematopoietic microenvironment and its surrounding tissues, we have
      generated stromal clones from subdissected day 10 and day 11 AGMs, embryonic
      livers (ELs) and gut mesentery. We here examine the ability of 19 of these clones
      to sustain extended long-term cultures (LTCs) of human CD34(+) umbilical cord
      blood (UCB) cells in vitro. The presence of in vitro repopulating cells was
      assessed by sustained production of progenitor cells (extended LTC-CFC) and
      cobblestone area-forming cells (CAFC). The embryonic stromal clones differed
      greatly in their support for human HSCs. Out of eight clones tested in the
      absence of exogenous cytokines, only one (EL-derived) clone was able to provide
      maintenance of HSCs. Addition of either Tpo or Flt3-L + Tpo improved the long
      term support of about 50% of the tested clones. Cultures on four out of 19
      clones, ie the EL-derived clone mentioned, two urogenital-ridge (UG)-derived
      clones and one gastrointestinal (GI)-derived clone, allowed a continuous
      expansion of primitive CAFC and CFU-GM with over several hundred-fold more
      CAFC(week6) produced in the 12th week of culture. This expansion was considerably
      higher than that found with the FBMD-1 cell line, which is appreciated by many
      investigators for its support of human HSCs, under comparable conditions. This
      stromal cell panel derived from the embryonic regions may be a powerful tool in
      dissecting the factors mediating stromal support for maintenance and expansion of
      HSCs.

PMID- 12200696
TI  - Chemotherapy targeting methylthioadenosine phosphorylase (MTAP) deficiency in
      adult T cell leukemia (ATL).
AB  - Methylthioadenosine phosphorylase (MTAP) is an important enzyme used for the
      salvage of adenine and methionine. Cells lacking this enzyme are expected to be
      sensitive to purine synthesis inhibitors and/or methionine starvation. We
      reported previously that the MTAP gene is deleted in adult T cell leukemia (ATL)
      cells. In the present study, we expanded our series and used a real-time
      quantitative PCR assay for accurate diagnosis of the deletion and nine of 65
      primary ATL samples (13.8%) were MTAP negative. In spite of this low incidence,
      ATL cells showed significantly higher sensitivity to L-alanosine, an inhibitor of
      de novo adenosine monophosphate (AMP) synthesis, than normal lymphocytes,
      suggesting that the MTAP gene is inactivated not only by deletion but also by
      other mechanisms. Indeed, a real-time quantitative RT-PCR assay disclosed that
      primary ATL cells had significantly lower MTAP mRNA expression than normal
      lymphocytes. Since MTAP-negative ATL cell lines also showed much higher
      sensitivity to L-alanosine than MTAP-positive ATL cell lines, we used these cell
      lines to investigate whether it is possible to develop selective therapy
      targeting MTAP deficiency. A substrate of MTAP, methylthioadenosine (MTA) or its
      substitutes rescued concanavalin A (Con A)-activated normal lymphocyte
      proliferation from L-alanosine toxicity. All the compounds except 5'
      deoxyadenosine, however, also caused the undesirable rescue of MTAP-negative ATL
      cell lines. 5'-Deoxyadenosine had the desired ability to rescue hematopoietic
      progenitor cells without rescuing ATL cell lines. These results support the
      rationale for a chemotherapy regimen of L-alanosine combined with 5'
      deoxyadenosine rescue in MTAP-deficient ATL.

PMID- 12200695
TI  - HERG potassium channels are constitutively expressed in primary human acute
      myeloid leukemias and regulate cell proliferation of normal and leukemic
      hemopoietic progenitors.
AB  - An important target in the understanding of the pathogenesis of acute myeloid
      leukemias (AML) relies on deciphering the molecular features of normal and
      leukemic hemopoietic progenitors. In particular, the analysis of the mechanisms
      involved in the regulation of cell proliferation is decisive for the
      establishment of new targeted therapies. To gain further insight into this topic
      we report herein a novel approach by analyzing the role of HERG K(+) channels in
      the regulation of hemopoietic cell proliferation. These channels, encoded by the
      human ether-a-go-go-related gene (herg), belong to a family of K(+) channels,
      whose role in oncogenesis has been recently demonstrated. We report here that
      herg is switched off in normal peripheral blood mononuclear cells (PBMNC) as well
      as in circulating CD34(+) cells, however, it is rapidly turned on in the latter
      upon induction of the mitotic cycle. Moreover, hergappears to be constitutively
      activated in leukemic cell lines as well as in the majority of circulating blasts
      from primary AML. Evidence is also provided that HERG channel activity regulates
      cell proliferation in stimulated CD34(+) as well as in blast cells from AML
      patients. These results open new perspectives on the pathogenetic role of HERG
      K(+) channels in leukemias.

PMID- 12200697
TI  - Schedule-dependent synergism and antagonism between methotrexate and cytarabine
      against human leukemia cell lines in vitro.
AB  - Methotrexate (MTX) and cytarabine have been widely used for the treatment of
      acute leukemias and lymphomas for over 30 years. However, the optimal schedule of
      this combination is yet to be determined and a variety of schedules of the
      combination has been used. We studied the cytotoxic effects of MTX and cytarabine
      in combination against human leukemia cell lines at various schedules in vitro.
      The effects of the combinations at the concentration of drug that produced 80%
      cell growth inhibition (IC(80)) were analyzed using the isobologram method of
      Steel and Peckham. Simultaneous exposure to MTX and cytarabine for 3 days
      produced antagonistic effects in human T cell leukemia, MOLT-3 and CCRF-CEM, B
      cell leukemia, BALL-1, Burkitt's lymphoma, Daudi, promyelocytic leukemia, HL-60
      and Philadelphia chromosome-positive leukemia, K-562 cells. Simultaneous exposure
      to MTX and cytarabine for 24 h produced antagonistic effects, sequential exposure
      to MTX for 24 h followed by cytarabine for 24 h produced synergistic effects, and
      the reverse sequence produced additive effects in both CCRF-CEM and HL-60 cells.
      Sequential exposure to MTX for 24 h followed by cytarabine for 3 days also
      produced synergistic effects in MOLT-3 cells. Cell cycle analysis supported these
      observations. Our findings suggest that the simultaneous administration of MTX
      and cytarabine is not appropriate and the sequential administration of MTX
      followed by cytarabine may be the optimal schedule of this combination.

PMID- 12200698
TI  - Human AML cells in NOD/SCID mice: engraftment potential and gene expression.
AB  - Most cases of human acute myeloid leukemia (AML) engraft in irradiated non-obese
      diabetic/severe combined immunodeficient (NOD/SCID) mice. Intravenous transfer of
      as few as 10(5) human AML cells resulted in engraftment. Cases with poor
      prognosis clinical features, including FLT3 mutations, tended to engraft
      efficiently. Nevertheless, AML cells obtained from patients at relapse did not
      engraft more efficiently than cells obtained from the same patients at initial
      diagnosis. One passage of human AML cells in NOD/SCID mice did not appear to
      select for increased virulence, as measured by serial transplantation efficiency.
      Finally, cDNA microarray analyses indicated that approximately 95% of genes were
      expressed at similar levels in human AML cells immunopurified after growth in
      mice, as compared to cells assessed directly from patients. Thus, the growth of
      human AML cells in NOD/SCID mice could yield large numbers of human AML cells for
      direct experimental use and could also function as a renewable, potentially
      unlimited source of leukemia cells, via serial transplantation.

PMID- 12200699
TI  - F-MuLV acceleration of myelomonocytic tumorigenesis in SV40 large T antigen
      transgenic mice is accompanied by retroviral insertion at Fli1 and a novel locus,
      Fim4.
AB  - We describe here the development of a murine system for the identification of
      genes involved in myelomonocytic neoplasms. Transgenic C57BL/6J mice expressing
      SV40 early region under a myelomonocytic promoter develop histiocytic sarcomas
      with a latency of 167 days. We used retroviral proviral tagging to accelerate
      tumorigenesis and to uncover genetic changes that contribute to tumor
      development. Infection of transgenic mice with Friend murine leukemia virus (F
      MuLV) shortened the latency of morbidity to 103 days (P< 0.001); this was
      associated with clonal proviral integrations in tumor DNA. As expected for F
      MuLV, proviral insertions occurred at Fli1 in both transgenic and nontransgenic
      tumors. Four insertions were found at a novel locus, termed Fim4, on chromosome
      6. This region is syntenic to human 7q32, a region that is commonly deleted in
      human myelodysplastic syndrome and acute myeloid leukemia. A murine BAC
      containing Fim4 was sequenced and analyzed, and while there was significant human
      mouse homology in the area of the insertions, no candidate gene has been
      identified. Thus we have established a system to identify genes involved in
      myelomonocytic tumors, and have used it to identify Fim4, a new common site of
      proviral insertion. Study of this locus may provide insight into genes involved
      in AML-associated 7q32 deletions in humans.

PMID- 12200700
TI  - Clinical activity of arsenic trioxide for the treatment of multiple myeloma.
AB  - Arsenic has been used since ancient times as a therapeutic agent. However, until
      recently its use in modern medicine has been restricted to the treatment of a
      limited number of parasitic infections. In the early 1990s, reports from China
      described impressive results with arsenic trioxide in patients with de novo,
      relapsed, and refractory acute promyelocytic leukemia (APL). Other investigators
      subsequently confirmed these results leading to approval of its use for relapsed
      or refractory APL in the United States. Investigations of this agent have
      demonstrated that its efficacy in APL and preclinical tumor models is dependent
      upon a number of mechanisms, including induction of apoptosis, effects on
      cellular differentiation, cell cycling, and tumor angiogenesis. Subsequent
      preclinical studies showed significant activity of arsenic trioxide in multiple
      myeloma (MM). Based on this, in a phase II trial, we have evaluated the activity
      of arsenic trioxide in 14 patients with relapsed MM, refractory to conventional
      salvage therapy. With the dose and schedule used, treatment with arsenic trioxide
      produced responses in three patients and prolonged stable disease in a fourth
      patient, with the longest response lasting 6 weeks. Although treatment was
      reasonably well tolerated, in these patients with extensive prior therapy, 11
      developed cytopenia, five associated with infectious complications and three
      developed deep vein thromboses. The results of this small trial support further
      investigation of this novel drug for the treatment of patients with relapsed or
      refractory MM.

PMID- 12200701
TI  - Long-term results (12 years) of high-dose therapy in 127 patients with de novo
      multiple myeloma.
AB  - This report describes the long-term outcome of a cohort of 127 de novo multiple
      myeloma patients treated with at least one course of high-dose therapy (HDT) in a
      single institution between June 1985 and December 1995, for whom the minimum
      follow-up duration for survivors is 6 years. The 12-year overall survival (OS)
      and event-free survival (EFS) rates are 24.9% and 3.1%, respectively, and the
      median survival and EFS are 49 and 17 months, respectively. Only four patients
      are alive and disease-free 79, 90, 132 and 153 after the first HDT, respectively.
      Three of them received a subsequent allogeneic bone marrow transplantation. Three
      factors significantly influence OS in this series: B2M at diagnosis, age, and the
      completion of a second HDT. The 10-year survival is 18.9% for the group of
      patients with B2M level >3 mg/l at diagnosis as compared with 41% for patients
      with B2M < or =3, with a median survival of 31 months vs 73 (P = 0.01). The 10
      year survival is 23.4% for the group of patients aged >55 years as compared with
      36.5% for patients aged <55 years, with a median survival of 34.5 months vs 70.5
      (P = 0.04). The 10-year survival is 20.4% for the group of patients who did not
      receive a second HDT as compared with 35.2% for patients who completed a second
      HDT, with a median survival of 29 months vs 70 (P = 0.02). In this study we show
      that some patients treated with HDT experience durable remission and prolonged
      survival. This survival is significantly influenced by age (< or =55 years), B2M
      at diagnosis (< or =3 mg/l) and by the completion of two cycles of HDT.

PMID- 12200702
TI  - Alterations of the cyclin D1/pRb/p16(INK4A) pathway in multiple myeloma.
AB  - The retinoblastoma protein (pRb), p16(INK4A), D-type cyclins, and their partners
      cyclin-dependent kinase (CDK) 4 and 6 constitute a G(1) regulatory pathway
      commonly targeted in tumorigenesis. Several malignancies show a reciprocal
      correlation between genetic alterations of single members of the pRb pathway.
      Therefore, we determined the frequency of Rb deletions and cyclin D1 alterations
      by fluorescence in situ hybridization as well as 5' CpG island hypermethylation
      of the p16(INK4A)gene using methylation-specific polymerase chain reaction in
      bone marrow mononuclear cells from 82 individuals with plasma cell disorders.
      Alterations in at least one of the components of the pathway were found in 75%.
      Cyclin D1 translocations or amplifications were detected in 14/82 (17.1%), Rb
      deletions at 13q14 in 23/82 (28%) of the cases, including three (3.6%) homozygous
      deletions. p16(INK4A) was hypermethylated in 33/57 (57.9%) of the samples.
      Further analysis revealed a highly significant correlation between cyclin D1
      alterations and extramedullar or leukemic myeloma manifestations (P = 0.014;
      Fisher's test). Whereas Rb deletions seemed to occur alternatively to cyclin D1
      alterations, no reciprocal correlation was found between p16(INK4A)
      hypermethylations and cyclin D1 or Rb locus aberrations. Cyclin D1 locus
      alterations and Rb deletions were associated with a significantly worse prognosis
      whereas p16(INK4A) hypermethylation had no impact on survival. We conclude that
      cyclin D1 and Rb aberrations seem to occur as alternative events in plasma cell
      malignancies and contribute to clinical course and prognosis. In contrast,
      although p16(INK4A) hypermethylation is frequent, inactivation of p16(INK4A)
      seems not to be involved in the pathogenesis of plasma cell disorders.

PMID- 12200703
TI  - Distribution of BCL2 breakpoints in follicular lymphoma and correlation with
      clinical features: specific subtypes or same disease?
AB  - The t(14;18)(q32;q21) translocation is closely associated with follicular
      lymphoma (FL), and is routinely assessed with molecular methods exploring BCL2
      breakpoints for both diagnosis and minimal residual disease (MRD) monitoring. We
      and others have previously reported new recurrent breakpoints (3'BCL2 and 5'mcr)
      which could be easily analyzed. In this study, we characterized the BCL2
      breakpoints in 113 untreated patients with t(14;18)-positive FL and correlated
      their location with the location of JH break and with the clinical features.
      Breakpoints were respectively located at the major breakpoint region (MBR) in 73
      cases (65%), at the minor cluster region (mcr) in 10 cases (9%), at 3'BCL2 in 14
      cases (12%) and at 5'mcr in seven cases (6%). Finally, the breakpoint could not
      be located in nine patients (8%). 5'mcr cases were associated with bulky and high
      stage disease, with frequent extranodal involvement and bone marrow infiltration.
      Survival studies did not show any correlation between breakpoint location and
      clinical outcome. The joining JH6 segment was the most frequently involved
      whatever the breakpoint location. In conclusion, unusual BCL2 breakpoints are
      found in about 20% of newly diagnosed follicular lymphomas and their study should
      be considered in the investigation of BCL2-JH rearrangement. It was not possible,
      in this series, to demonstrate any correlation between breakpoint location and
      either initial characteristics of the disease or survival of the patients.

PMID- 12200704
TI  - BCL-6 mRNA expression in higher grade transformation of follicle center lymphoma:
      correlation with somatic mutations in the 5' regulatory region of the BCL-6 gene.
AB  - Follicle center lymphoma (FCL) is an indolent low-grade B cell non-Hodgkin's
      lymphoma (NHL) that frequently transforms to aggressive diffuse large B cell
      lymphoma (DLBCL). Histological transformation of FCL is commonly associated with
      accumulation of secondary genetic alterations. The BCL-6 gene is commonly
      implicated in the pathogenesis of DLBCL and its expression may be altered by
      clonal rearrangements and somatic point mutations in its 5' non-translated
      regulatory region. Recently, somatic mutations of the BCL-6 gene were associated
      with the transformation process. Here, we examined BCL-6 mRNA expression and BCL
      6 mutations in paired biopsies from the same patients obtained at the time of FCL
      diagnosis and after transformation. BCL-6 mRNA expression markedly increased upon
      transformation (1.9- to 4.8-fold) in three cases, remained unchanged in one case
      and decreased compared to the diagnosis FCL specimens in four cases. The three
      specimens that demonstrated an increase in the BCL-6 mRNA expression upon
      transformation harbored BCL-6 gene mutations in the 5' region of the first intron
      that overlapped with the previously reported negative regulatory region of the
      gene. Accumulation of new mutations in this region was not observed in DLBCL
      biopsies in which the BCL-6 mRNA expression did not increase. The present study
      demonstrates that although BCL-6 gene mutations do accumulate during the
      transformation process and, depending on their location within the first intron,
      may deregulate BCL-6 mRNA expression, increase in BCL-6 mRNA expression is not
      uniformly required for transformation from FCL to DLBCL.

PMID- 12200705
TI  - The novel t(11;12;18)(q21;q13;q21) represents a variant translocation of the
      t(11;18)(q21;q21) associated with MALT-type lymphoma.

PMID- 12200706
TI  - Differential bone marrow aspirate DNA yields from commercial extraction kits.

PMID- 12200707
TI  - Mutation of the AML1/RUNX1 gene in a transient myeloproliferative disorder
      patient with Down syndrome.

PMID- 12200708
TI  - DNA profiling and cytogenetic analysis of cell line WSU-CLL reveal cross
      contamination with cell line REH (pre B-ALL).

PMID- 12200709
TI  - Sustained complete remission of recurrent acute myeloid leukaemia with a single
      dose of gemtuzumab ozogamicin and low-dose interleukin-2 maintenance.

PMID- 12200710
TI  - Complete remission in hypoplastic acute myeloid leukemia induced by G-CSF without
      chemotherapy: report on three cases.

PMID- 12200711
TI  - Additional evidence of genetic changes in children with ALL and TEL/AML1 fusion
      gene.

PMID- 12200712
TI  - Cultures of myeloid progenitor cells in pediatric essential thrombocythemia.

PMID- 12200714
TI  - Liposomal daunorubicin (DaunoXome) for treatment of relapsed meningeal acute
      myeloid leukemia.

PMID- 12200713
TI  - Identification and characterization of rapidly dividing U937 clones with
      differential telomerase activity and gene expression profiles: role of c-Myc/Mad1
      and Id/Ets proteins.

PMID- 12200715
TI  - Increased risk of human herpesvirus-8 infection in patients with adult T cell
      leukemia/lymphoma in Okinawa.

PMID- 12200716
TI  - In vitro glucocorticoid resistance in childhood leukemia correlates with receptor
      affinity determined at 37 degrees C, but not with affinity determined at room
      temperature.

PMID- 12200717
TI  - Treatment of HBV-carrying lymphoma patients with Rituximab and CHOP: a diagnostic
      and therapeutic challenge.

PMID- 12200718
TI  - Mechanisms of resistance to nucleoside analogue chemotherapy in mantle cell
      lymphoma: a molecular case study.

PMID- 12200719
TI  - Blastic variant of mantle cell lymphoma occurring in immunosuppressed patients.

PMID- 12200720
TI  - Therapy-related myelodysplastic syndrome or acute myelogenous leukemia in
      patients with acute promyelocytic leukemia (APL).

PMID- 12200722
TI  - A potential role of erythropoietin in angiogenesis associated with
      myelodysplastic syndromes.

PMID- 12200724
TI  - [What consequences will have the introduction of German Diagnosis Related Groups
      (G-DRGs) in surgical departments?].
AB  - With the planned introduction of Diagnosis related groups (DRG) in the German in
      patient reimbursement system an economic brake will be put on the hospitals. The
      upcoming expected growth of the older German population and the ongoing process
      of better diagnostic and therapeutic procedures leads to a gap between costs and
      resources in the established health care system. With the introduction of the
      DRGs starts a process of one payment for one main diagnosis in hospital care.
      This requires a better resource control and leads to a tightrope walk between
      medical and economic aspects. The short time consequences result in great efforts
      of correct coding of diagnoses and procedures, as a survival strategy for
      surgical departments. More or less are new structures necessary, the development
      of "clinical pathways" and the increase or decrease of capacities will become the
      main tasks in the next years.

PMID- 12200725
TI  - [First experiences with clinical pathways in carotid surgery].
AB  - The introduction of guidelines for carotid surgery into praxis. Early experiences
      with the clinical pathway. With the use of DRG's for reimbursements, a new
      organization of clinical pathways may play an increasingly important role in the
      delivery of health care. The impact of clinical pathways as a management tool in
      the treatment of patients with carotid occlusive disease was studied.
      Representatives of all involved disciplines identified in which sequence, where,
      when, by whom and which care a patient with carotid disease should receive. The
      individual steps of care were analysed, estimating their utility and determining
      a new plan for a patient's care. The clinical pathway specifies a target time
      window, defining exactly the internal and external logistics. The early
      experiences demonstrate that clinical pathways can be a useful tool for improving
      the quality of health care by improving cost and process transparency. Hospital
      length of stay was reduced by 2.3 days.

PMID- 12200727
TI  - [Results and complications of ruptured abdominal aortic aneurysm repair].
AB  - During 1993 to 2000 85 patients were treated for a ruptured abdominal aortic
      aneurysm. The average age of the patients was 72.4 years (46-90). 71 patients
      showed an infrarenal rupture and the remaining 14 a suprenal rupture. 76 of 85
      cases were covered ruptures. All patients were operated upon. A tube graft was
      required in 43 cases and 31 needed a bifurcated graft. In further two cases an
      extraanatomical bypass was necessary due to a mycotic aneurysm. The operation on
      11 patients could not be completed and 21 patients died in hospital during the
      postoperative period. On the other hand, 53 patients survived the rupture of the
      aneurysm. The mortality rate was 37.6 %. The early non-surgical complications
      dominated during the postoperative period. Respiratory failure, renal failure and
      cardiac failure were responsible for the mortality rate. It is unforseeable which
      patients will survive the emergency operation. Therefore it is always appropriate
      to attempt the reconstruction of an acutely ruptured AAA.

PMID- 12200726
TI  - [Results of endovascular Abdominal Aortic Aneurysm Repair (EVAR)].
AB  - Endovascular surgery for abdominal aortic aneurysms (AAA) has been performed with
      different commercially available devices since more than 7 years. The technique
      of implantation even for ruptured aneurysm is feasible. Attention is now focused
      on complications and mid-term results. We present a single center experience over
      the last 7 years using nine different endografts. 653 patients with AAAs were
      treated endovascularly (158 tubes, 495 bifurcated) between August 1994 and
      September 2001. The total mortality rate in the follow-up period (median 37
      months) was 6.1 % with a 30-day mortality of 0.76 % and a procedure-related
      lethality of 1.2 %. Tube endografts showed the highest endoleakage rate (37.3 %)
      due to secondary shortening, migration and material defects. Endoleakage was
      diagnosed in 18.2 % of unibody designed stentgrafts versus 28.3 % in modular
      grafts. Regarding proximal Type I endoleaks suprarenal fixation with uncovered
      stents seems to be of no further advantage in proximal graft fixation. The
      conversion rate was 6.6 % (n = 43), aneurysm rupture following endovascular
      repair occurred in 3 of these patients (0.45 %). Mortality in emergency
      conversion was 30 % compared to no deaths in elective cases. There was a
      surprisingly high rate of inadvertent renal infarctions (9 %) in follow-up CT
      scans, two times higher in suprarenal fixation (18 %) than in infrarenal position
      (7.4 %). In conclusion, we observed best results in unibody bifurcated
      stentgrafts, late failure of first generation endografts (Mintec(R)) and
      decreasing conversion rates over the last years (learning curve!). The clinical
      significance of a side branch endoleak and related maximal AAA diameter remains
      uncertain. The ideal graft has yet to be found, but improvements in design and
      implantation techniques evolve rapidly. Good results will be obtained in the
      future by patient selection and restrictive indications.

PMID- 12200728
TI  - [How urgent is the operation of bilateral occlusion of the aortic bifurcation?].
AB  - INTRODUCTION: Symptoms of occluded aortic bifurcation are variable and
      consequently lead to the question "How urgent is the operation?". PATIENTS AND
      METHODS: The diagnostic and therapeutic procedure is analysed retrospectively in
      6 patients. The reason for the occlusion was thrombosis or embolism in 3 patients
      each. RESULTS: A successful bilateral inguinal thrombembolectomy was the standard
      operative revascularisation. In 2 of 3 emergency cases with critical ischemia the
      operation was performed without preoperative imaging. 3 patients with non
      critical ischemia were operated upon more than 12 hours after rising symptoms.
      DISCUSSION: How urgent the operation is depends primarily on the extent of
      occlusion. In case of critical ischemia a revascularisation can be performed
      without angiography. However, a more extensive procedure, even a bifemoral
      bifurcation graft, must be taken into account.

PMID- 12200729
TI  - [The acute mesenteric ischemia - not understood or incurable?].
AB  - PURPOSE: Despite surgical research and progress, the high mortality of acute
      intestinal ischemia seems to be improved insignificantly over the past fifty
      years. In this study we analyzed the specific diagnostic and therapeutic problems
      of the disease in order to improve further management of acute mesenteric
      ischemia. METHODS: From 1979 until 2000 64 patients (female 31, male 33) with a
      mean age of 64 (30-89) years underwent operation for primary intestinal ischemia
      at our institution. All medical and surgical records and imaging studies were
      reviewed retrospectively. Follow up consisted of clinical examination and duplex
      sonography. RESULTS: Only in 26 patients (41 %) a preoperative diagnostic work-up
      including angiography 12 and CT 14 was performed, whereas in 42 cases the
      intestinal ischemia was diagnosed during surgical exploration. Intestine
      malperfusion was caused primarily by venous thrombosis in 9 cases (14 %) and by
      arterial occlusive disease in 55 cases (86 %). Arterial disorders consisted of
      arterial thrombosis in 19 cases (30 %), arterial embolism in 18 cases (28 %),
      aortic or mesenteric artery dissection in 10 cases (15 %), non occlusive disease
      (NOD) in 5 cases (8 %), trauma 3 cases (5 %). Five different therapeutic
      strategies were applied: group I: Intestinal resection: 24 patients, anastomotic
      insufficiency 5 (39 %), mortality 11 (46 %), group II: intestinal artery
      revascularization: 5 patients, secondary patency rate 80 %, mortality 40 %, GROUP
      III: Intestinal artery revacularization and perfusion with Ringer's solution: 11
      patients, mortality 8 (73 %), group IV intestinal artery revascularization and
      intestinal resection: 3 patients, mortality 100 %, group V intestinal artery
      revascularization and perfusion and intestinal resection: 3 patients, mortality
      33 %. A second look operation was performed in 29 cases (40 %) and displayed
      malperfusion in 72 %. Only 21 of 64 patients survived the acute intestinal
      ischemia (in hospital mortality was 67 %). Delayed diagnostic and operation
      caused higher mortality (interval 10 hours: mortality 59 %, interval 37 hours
      mortality; 71 %, p = 0,06). Follow up after 61 (4-72) months of 21 patients (100
      %) could be achieved. Ten patients (48 %) had meanwhile died, 5 patients (50) %
      as consequence of mesenteric ischemia, the others of unrelated reasons. Eleven
      patients are still alive without clinical signs of intestinal ischemia.
      CONCLUSIONS: Early diagnosis before hospitalisation and in-hospital
      (arteriography) and operation are essential to improve the outcome of patients
      with acute intestinal ischemia. To avoid short bowel syndrome bowel resection
      should be combined with mesenteric revascularization. Resection of malperfused
      bowel should be done cautiously and should be followed automatically by second
      look operations. Special expertise and good team work of visceral and vascular
      surgeons are required to achieve better therapeutic results.

PMID- 12200731
TI  - [Vascular injuries after extremity trauma].
AB  - The aim of the present examination was to analyse extremity trauma with
      additional vascular injuries. Between 1973-2000 78 patients with traumatic
      peripheral vascular injuries have been treated at the Surgical Department of the
      University Hospital of Mannheim. In addition to clinical examination Doppler
      Duplex ultrasonography (cw-Doppler) was routinely performed. In selected cases
      either conventional or magnetic resonance angiography completed the diagnostic
      procedure. Vascular injuries to the upper extremities were found in 46.2 % (n =
      36) whereas 53.8 % (n = 42) of the patients suffered from trauma of the lower
      extremities. The popliteal artery was affected in 28.2 % followed by the brachial
      artery with 23.1 %. 52.6 % of the patients had interposition of autologous vein
      for reconstruction. Only 7.7 % of the cases needed interposition of alloplastic
      material. In general the injured extremity was immobilised by external fixation,
      followed by secondary vascular reconstruction. An efficient trauma management
      reduced amputation rate as low as 2.6 %.

PMID- 12200730
TI  - [Fistula Banding - Success-promoting Approach in Peripheral Steal Syndrome].
AB  - AIM: Evaluation of the diagnostic and therapeutic management of peripheral steal
      syndrome after placement of an autologous arteriovenous (av-) fistula and
      presentation of treatment results after its surgical correction. METHODS: During
      a time period from 1994 to 1999, 1 253 av-fistulas for hemodialysis were placed
      in our surgical department. Twenty-one patients (1.68 %) underwent service
      operations because of considerable lower perfusion of the hand. In 14 patients
      the av-fistula was ligated, whereas in 7 patients, a polytetrafluorethylene
      (PTFE) sleeve was implanted at the venous site for fistula "banding" to diminish
      blood flow. In addition to the clinical finding, pre-, intra- and postoperative
      blood flow rates were determined using Duplex ultrasonography. RESULTS: In
      patients showing flow rates of < 250 ml (carefully disclosed empiric value)
      ligation was chosen, whereas in cases with distinctly increased flow rates,
      banding of the arterialized vein was performed (authors' individually selected
      borderline flow). The extension of the banding was specified according to the
      intraoperatively determined flow rates. Recurrent steal syndrome was not observed
      over the entire postoperative observation period of 1-3 years. CONCLUSION:
      Arterial steal syndrome is a rare complication after placement of an av-fistula.
      In the majority of cases, surgical therapy is necessary. Pre- and intraoperative
      analysis of flow rates using Duplex ultrasonography may help to select the
      appropriate surgical approach and may, thus, determine the success rate of
      service operation.

PMID- 12200732
TI  - [Management of soft tissue injury in III B open tibial fractures: are local
      muscle flaps still up-to-date?].
AB  - Local muscle flaps for covering pretibial defects have been widely replaced due
      to the establishment of microsurgical procedures. The intention of the following
      study is to examine the results of soft tissue covering using local muscle flaps
      and to find out if its application is still indicated. At our level 1 trauma
      center 21 patients with III B open tibial fractures were treated with a local
      muscle flap to repair the soft tissue injury in the proximal and medial part of
      the lower leg. At the late follow-up after the average of 29 months all soft
      tissue defects and fractures were healed. Except of slight swelling under full
      weight stress no obstruction of blood circulation could be verified. 14 patients
      rated their functional outcome as good to excellent. In view of our results we
      consider local muscle flaps a suitable alternative to the free myoplasty for
      situations in which a more elaborate surgery is not feasible in due time, e. g.
      patients with acute brain edema, organ failure or lack of compliance.

PMID- 12200733
TI  - [Incisional hernia repair in Germany at the crossroads: a comparison of two
      hospital surveys in 1995 and 2001].
AB  - INTRODUCTION: Incisional hernia repair has become a controversial issue in
      surgery. METHODS: To survey the current practice patterns of incisional hernia
      repair, a questionnaire was mailed to 2 380 surgical departments in Germany.
      Responses were received from 732 hospitals. The results of the current survey
      were compared with that of a similar survey performed in 1995. RESULTS: Overall,
      the incidence of incisional hernia surgery seems to have markedly increased. An
      increasing number of operations is performed in specialized large centres.
      Depending on hernia type (primary hernia < 5 cm, primary hernia > 5 cm, recurrent
      hernia) mesh materials have gained popularity (15 %, 67 %, and 79 %,
      respectively) as compared to 1995. Prolene(R) (34 %) and Vypro(R) (25 %) are the
      currently preferred meshes. The number of hospitals that use non-resorbable
      suturing material has doubled between 1995 (22 %) and 2001 (45 %). Interrupted
      suture are no longer the standard technique for fascia closure (80 % in 1995, 50
      % in 2001). Autodermal skin graft and laparoscopic hernia repair are of little
      importance. Although literature data suggest high recurrence rates, most surgeons
      still expect that only 5-10 % of their primary or recurrent hernia repairs will
      fail. CONCLUSIONS: Incisional hernia repair is undergoing radical changes.
      However, it is unclear whether these changes in surgical techniques and materials
      were caused by the individual surgeon's clinical expertise, the recent
      publication of important trials, or the financial circumstances.

PMID- 12200735
TI  - [Long-term results after surgical therapy of Crohn's disease].
AB  - We performed a retrospective analysis in patients after operative therapy of
      Crohn's disease in our institution. PATIENTS AND METHODS: 81 patients that
      underwent surgery from 1990-1995 were analysed retrospectively. The follow up
      period in these patients was 42 months. RESULTS: In 81 patients a total of 88
      operations were performed. 56 patients were operated for the first time. The
      average patient's age was 35 years (range 14-76 years). Crohn's disease was
      located predominantly in the area of the ileocoecal valve. The most frequent
      operation was the ileocoecal resection. The prevalent operative indication in
      patients with small intestine Cohn's disease was the obstruction, in small
      intestine and colon manifestation the fistula. Complications in the early
      postoperative course appeared in 14 % of the patients. Postoperative mortality
      was 1.1 %. In a postoperative observation period of 3.5 years 3 of 57 patients (5
      %) had to undergo surgery again, due to recurrence. Altogether 25 of 81 (31 %)
      patients revealed a recurrence. CONCLUSIONS: The surgical therapy of Crohn's
      disease can be performed safely and provides long-term recurrence and complaint
      free periods.

PMID- 12200736
TI  - [Results of the Limberg transposition flap in the treatment of pilonidal sinus].
AB  - The surgical treatment of pilonidal sinus with the Limberg transposition flap
      will be demonstrated in 40 patients (22 male; 18 female). First step is draining
      the infect by incision, followed by radical excision of the pilonidal sinus and
      covering of the defect by a rhomboid transposition flap. In 39 out of 40 cases
      primary wound healing occurred. No recurrence has yet been encountered. In one
      case a seroma was observed which was drained and showed secondary wound healing.
      The mean hospital stay was 7.9 days and the mean time until return to work was
      about 15 days. We consider the Limberg transposition flap to be an effective
      treatment of pilonidal sinus disease due to its technical simplicity and low
      complication rate.

PMID- 12200737
TI  - [Primary synovial sarcoma of the lung - a rare tumor].
AB  - We present a 26 year old patient with a primary malignant synovial sarcoma of the
      lung that was observed for more than one year by a general practitioner and a
      pulmologist. Finally, because of recurrent hemoptysis a central tumor of
      mesenchymal origin of the left lower lobe was diagnosed by bronchoscopy. The
      invasion of the left atrium as far as to the mitral valve was diagnosed by MRT.
      The patient was operated on by extended pneumonectomy with extracorporeal
      circulation. The partial excision of the left atrium required plastic
      reconstruction. In the postoperative course the patient underwent chemo-therapy,
      6 cycles adriablastine/ifosfamid. 8 months after the first operation an extensive
      tumor recurrency occurred with infiltration of the chest wall. The patient
      refused further radio- or chemotherapy and died 14 months after the operation.
      Because of the small number of cases therapeutic strategy conceptions do not
      exist. The resection of the tumor is generally recommended. Chemo- and
      radiotherapy are accepted as an option for advanced tumor stage.

PMID- 12200738
TI  - [Small bowel obturation ileus related to ingestion of a medical device].
AB  - We report the case of a 50-year-old woman who was admitted to the hospital with
      an acute abdomen and underwent exploratory laparotomy. Intraoperatively, we
      suspected Crohn's disease of the ileocecal valve and decided to treat
      conservatively. However, in the further clinical course the patient became
      severely sick and developed a necrotizing ileocecal inflammation in combination
      with multiple perforations, 4-quadrants peritonitis and several other
      complications. Histopathology revealed an unspecific inflammation of the
      ileocecal valve. Furthermore, numerous little cellulose sponges were found in the
      resected intestinal segment. They were obstructing the lumen and were identical
      with the contents of an appetite suppressing medical device. A connection between
      the ingestion of this medical device and the penetrating inflammation of the
      ileocecal valve has to be suspected.

PMID- 12200739
TI  - Clinical and laboratory findings in twins with neonatal epileptic encephalopathy
      mimicking aromatic L-amino acid decarboxylase deficiency.
AB  - Aromatic L-amino acid decarboxylase (AADC) is a vitamin B 6 requiring enzyme
      involved in the biosynthesis of the neurotransmitters dopamine (DA) and
      serotonin. Lack of AADC leads to a combined deficiency of the catecholamines DA,
      norepinephrine (NE), epinephrine (E) as well as of serotonin. Here we describe
      premature twins who presented with severe seizures, myoclonus, rotatory eye
      movements and sudden clonic contractions. The patients showed an improvement of
      the clonic contractions under vitamin B 6 supplementation but died in the third
      week of life. In CSF and urine a biochemical pattern indicative of AADC
      deficiency was revealed. Concentrations of homovanillic acid (HVA), 5
      hydroxyindoleacetic acid (5-HIAA) and 3-methoxy-4-hydroxyphenylglycol (MHPG) were
      decreased, in association with increased concentrations of 3-ortho-methyldopa (3
      OMD) in CSF and significantly increased vanillactic acid in urine. The AADC
      enzyme substrates L-dopa and 5-hydroxytryptophan (5-HTP) were elevated in CSF.
      Elevated concentrations of threonine as well as of an unidentified compound in
      CSF rounded off the biochemical pattern. AADC activity was found to be increased
      in plasma and deficient in the liver. Molecular studies effectively ruled out a
      genetic defect in the AADC gene. The basis for the epileptic encephalopathy in
      the twins may be located in the metabolism of vitamin B 6 and remains to be
      defined.

PMID- 12200740
TI  - Outcome in children with space-occupying posterior fossa arachnoid cysts.
AB  - While prognostic information for Dandy-Walker syndrome and non-progressive
      cerebellar ataxia/cerebellar hypoplasia is available, surprisingly scant
      literature reports are found for space-occupying posterior fossa arachnoid cysts
      (PFAC). We describe the outcome of patients with symptomatic PFAC shunted as
      infants. Only 11 children were seen over a 20-year period (1980-1999). Cyst
      location was retrocerebellar (n = 8), supravermian (n = 2) and in the
      cerebellopontine angle (n = 1). Motor and cognitive impairments in one child were
      interpreted as the result of neurosurgical complications (intraventricular and
      intracerebral haemorrhage). One 6-year-old boy had mild truncal ataxia and mild
      cognitive delay. The 9 other patients had no evidence of ataxia or clumsiness and
      had average, some even above average, cognitive ability and scholastic
      achievements. Epilepsy was not a feature. We conclude that the prognosis of PFAC
      for cognitive development and neurological signs is favourable.

PMID- 12200741
TI  - Treatment and long-term prognosis of myoclonic-astatic epilepsy of early
      childhood.
AB  - PURPOSE: We retrospectively studied patients with myoclonic-astatic epilepsy of
      early childhood (MAE) to investigate the most effective treatment and long-term
      seizure and intellectual prognosis. SUBJECTS: Eighty-one patients with MAE were
      recruited from among 3600 patients with childhood epilepsy according to the ILAE
      criteria of MAE. METHODS: We retrospectively investigated the clinical
      characteristics and ultimate prognosis of the patients with MAE from the medical
      records. The effects of various antiepileptic drugs, ketogenic diet and ACTH
      treatments on myoclonic-astatic seizures (MS/AS), apparently a hallmark of this
      unique epileptic syndrome, were also studied. RESULTS: MS/AS in 89 % of the
      patients disappeared within 1 to 3 years despite initial resistance, but
      generalized tonic-clonic or clonic seizures [G(T)CS] tended to continue. The most
      effective treatment for the MS/AS was ketogenic diet, followed by ACTH and ESM.
      At the last follow-up, 55 patients or 68 % of all the patients had remission of
      epilepsy, 11 patients or 14 % experienced a recurrence of GTCS after a long
      remission period but easily regained control, and the remaining 15 patients or 18
      % continued to have seizures and intellectual outcomes were poor. In one half of
      these patients with poor outcomes, repeated minor epileptic status and nocturnal
      generalized tonic seizures persisted. A family history of epilepsy and a
      combination of minor epileptic status are risk factors for poor outcomes.
      CONCLUSION: MAE is considered to form a clinical spectrum ranging in its main
      seizure type from myoclonic to atonic, and in seizure and intellectual outcomes
      from benign to malignant. The overall prognosis, despite initial resistance to
      treatment, appears to be much better than originally thought when ILAE
      definitions excluding SME are followed.

PMID- 12200742
TI  - Prognostic value of EEG depression in preterm infants for later development of
      cerebral palsy.
AB  - The aim of this study is to examine the most appropriate timing for EEG
      recordings in order to predict the risk of cerebral palsy (CP) on the basis of
      the degree of acute stage abnormalities (ASA) in preterm infants. We
      retrospectively investigated the correlation between the degree of ASA and
      psychomotor outcome of 295 infants born between 27 and 32 weeks of gestational
      age whose initial EEG recording was performed within 7 days of life. Forty-six
      infants were diagnosed as having CP at 18 months of corrected age, and most of
      them suffered from diplegia due to periventricular leukomalacia (PVL). The
      maximum degree of ASA correlated with a later development of CP and its severity.
      Correlation between the degree of ASA and the severity of CP was highest on day 1
      - 2, but this tendency was less clear after day 3. Specificity and negative
      predictive value were generally high within the first 7 days of life. But
      sensitivity was markedly decreased after day 3, and positive predictive value was
      highest on day 2. An EEG on day 1 or 2 will be useful in order to predict
      developmental outcome of preterm infants on the basis of the grade of ASA.

PMID- 12200743
TI  - Positron emission tomography shows reduced striatal dopamine D1 but not D2
      receptors in juvenile neuronal ceroid lipofuscinosis.
AB  - We studied striatal dopamine D1 and D2 receptors in patients with juvenile
      neuronal ceroid lipofuscinosis (JNCL) with positron emission tomography (PET)
      using a dopamine D1 receptor antagonist [11C]NNC 756 and a dopamine D2 receptor
      antagonist [11C]raclopride as ligands. The mean [11C]NNC 756 uptake value in JNCL
      was reduced by 15 % from the mean control value in the putamen (p < 0.01) and by
      13 % in the caudate nucleus (p < 0.01). The mean [11C]raclopride uptake in JNCL
      patients was not significantly different from the mean of the control group
      either in the putamen or the caudate nucleus. Our results show a mild reduction
      in striatal dopamine D1 but not in D2 receptors in JNCL, indicating slightly
      impaired striatal neuronal function. The contribution of these changes to the
      extrapyramidal symptoms of the patients and their treatment deserves further
      studies.

PMID- 12200744
TI  - Alteration of serotonergic receptors in the brain stems of human patients with
      respiratory disorders.
AB  - We compared the developmental changes of 5-hydroxytryptamine (5-HT) 1 A and 5-HT2
      A receptor immunoreactivity in the nuclei in relation to the cardiorespiratory or
      autonomic function in the human brain stem in sudden infant death syndrome (SIDS)
      and congenital central hypoventilation syndrome (CCHS) patients and age-matched
      controls by means of immunohistochemical methods. There were significant
      decreases in 5-HT1 A and 5-HT2 A receptor immunoreactivity in the dorsal nucleus
      of the vagus, solitary nucleus and ventrolateral medulla in the medulla
      oblongata, and significant increases in the periaqueductal gray matter (PAG) of
      the midbrain in SIDS victims, but there were no significant differences between
      those in CCHS patients and controls. The decreased immunoreactivity of the
      receptors in the medulla oblongata was accompanied by brain stem gliosis.
      Therefore, the decreases in the receptors may be secondary to chronic hypoxia or
      repeated ischemia, but may be causally related to some impairment of the
      developing cardiorespiratory neuronal system. As 5-HT1 A and 5-HT2 A receptors
      were the most abundant in the fetal period and then decreased with subsequent
      development, the increases in 5-HT1 A and 5-HT2 A receptor immunoreactivity in
      PAG may reflect delayed neuronal maturation, but may also reflect compensatory
      changes in response to hypofunctioning serotonergic neurons in the medulla
      oblongata in SIDS. There was no abnormal expression of 5-HT1 A and 5-HT2 A
      receptors in CCHS brain stems, and so the pathophysiology seems to be different
      between SIDS and CCHS patients.

PMID- 12200745
TI  - MRI lesions and infants with neonatal encephalopathy. Is the Apgar score
      predictive?
AB  - OBJECTIVE: The aim of this study was to establish whether, in full-term infants
      presenting with neonatal encephalopathy, the 1 minute Apgar score gives an
      indication of the presence, site or type of lesions observed on brain MRI in the
      neonatal period. PARTICIPANTS AND METHODS: The study cohort included 157 full
      term infants who had neurological abnormalities during the first 48 hours after
      delivery. Infants with developmental, genetic, infective or metabolic diagnoses
      were excluded from the study. The infants were subdivided according to their 1
      minute Apgar score into three groups as follows: Apgar score 0 - 3 (n = 108/157,
      69 %), 4 - 7 (n = 29, 19 %), 8 - 10 (n = 21, 12 %). Results. Severe and moderate
      basal ganglia and thalamic (BGT) lesions, with one exception, were only observed
      in the group with an Apgar score of 3 or below. Minimal BGT lesions were, with
      one exception, associated with scores below 7 and mainly below 3. However, not
      all the infants with low Apgar scores had BGT lesions and 28 % of the patients
      with Apgar scores below 3 had normal scans or only minimal white matter changes.
      White matter lesions without BGT involvement were equally distributed in the
      cohort, irrespective of the Apgar scores. Cerebral infarction and scattered white
      matter haemorrhages were the most common findings in infants with Apgar scores of
      4 and above. The Apgar scores were not always predictive of motor outcome at 2
      years but the presence and severity of the sequelae mainly reflected the site and
      severity of MRI findings. CONCLUSIONS: These findings stress the importance of
      subdividing neonatal encephalopathy into diagnostic categories according to brain
      lesions if one wishes to study either causative factors or outcome.

PMID- 12200746
TI  - Effects of oral creatine supplementation in a patient with MELAS phenotype and
      associated nephropathy.
AB  - An 18-year-old male patient with MELAS phenotype and 2 previous episodes of
      cerebral stroke, recurrent seizures and nephropathy, was treated with creatine
      monohydrate after the acute onset of psychomental regression and changing states
      of somnolence and aggressive and agitated behaviour. These symptoms disappeared
      completely after 4 weeks of treatment with creatine after which the patient
      regained all his previous mental abilites. Brain (white matter) proton magnetic
      resonance spectroscopy (chemical shift imaging) performed at 6 and 12 months of
      treatment showed lactic acid (Lac) accumulation and high creatine (Cr) levels in
      relation to choline-containing compounds (Cho). Urinary creatinine excretion as
      an indicator of the muscle and brain creatine pool increased upon short-term (12
      days) high-dosage creatine supplementation (20 g per day) while plasma creatinine
      concentrations as possible indicators both of increasing creatine pool and of
      renal insufficiency increased during the course (28 months) of low-dosage
      creatine supplementation (5 g per day). Deterioration of renal function was
      finally indicated by urea retention and by impairment of renal creatinine
      clearance. These observations suggest that creatine supplementation may have a
      neuroprotective effect in patients with MELAS and episodes of acute mental
      deterioration. Adverse effects of creatine supplementation on renal function must
      be considered especially in patients with preexisting nephropathy.

PMID- 12200747
TI  - Brain reorganisation in cerebral palsy: a high-field functional MRI study.
AB  - Early brain damage may induce alternative organisation of cortical brain
      functions. This may happen even if there is no damage to the cortex. We assessed
      a 15-year-old girl with a perinatal left-sided subcortical lesion without
      cortical damage by functional MRI at 3 Tesla. The patient had congenital
      hemiparesis, mirrored limb movements and normal language function. Functional MRI
      was used to assess language using orthographic-lexical retrieval and noun-verb
      generation tasks, and demonstrated right-sided language dominance. Functional MRI
      of motor function was assessed for both hands separately, by squeezing a rubber
      balloon. Both hand movements induced asymmetric bilateral activation of the motor
      cortex, with a predominance of contralateral activation. Language-associated
      activity is usually left-hemispheric, but was found in the undamaged right-sided
      hemisphere. Motor function was associated with the unusual pattern of bilateral
      cortical activation. The MR findings explain the clinical features and suggest
      widespread alternative cortical organisation in the presence of a focal lesion
      confined to subcortical structures.

PMID- 12200748
TI  - Psychogenic contractures: the magic side of medicine.

PMID- 12200749
TI  - Lipid compositional differences of small, dense low-density lipoprotein particle
      influence its oxidative susceptibility: possible implication of increased risk of
      coronary artery disease in subjects with phenotype B.
AB  - An increased susceptibility of low-density lipoprotein (LDL) to lipid
      peroxidative modification may be a key factor in the higher risk of coronary
      artery disease (CAD) among subjects with phenotype B. Compositional differences
      in the LDL particle may also be implicated in its atherogenicity and, in
      particular, may be associated with varying degrees of oxidative susceptibility of
      LDL, although this remains unclear. We hypothesized that the oxidative
      susceptibility of small, dense LDL was directly influenced by its lipid
      composition, which may lead to an increased risk of CAD in subjects with
      phenotype B. To test this hypothesis, we compared the differences in lipid
      compositions of LDL particles from subjects with phenotype A and those with
      phenotype B, and investigated the direct association of lipid composition with
      susceptibility to lipid peroxidative modification in 102 subjects who underwent a
      coronary angiographic examination. Subjects with phenotype B (n = 52) had a
      significantly higher incidence of CAD than subjects with phenotype A (77% v 44%;
      P <.005). In comparing the oxidative susceptibility of LDL, the lag time was
      significantly reduced in subjects with phenotype B compared to phenotype A (48.7
      +/- 8.6 v 41.5 +/- 5.5 minutes; P <.0001). In addition, the lag time showed a
      positive correlation with LDL-peak particle diameter (PPD) (r = 0.324, P <.005).
      Lipid composition per LDL particle was expressed as the ratio of lipid content to
      apolipoprotein B (apoB) content (wt/wt). Subjects with phenotype B showed a
      significant depletion in the contents of free-cholesterol (FC), cholesterol ester
      (CE), and phospholipid (PL) per particle compared to subjects with phenotype A,
      although there was no significant difference in the triglyceride (TG) content per
      LDL particle. Except for TG, the lipid content per LDL particle showed a
      significant positive correlation with lag time in all subjects. Moreover,
      increased susceptibility of small, dense LDL to lipid peroxidative modification
      was most strongly associated with a depleted FC content per LDL particle. In
      conclusion, the greater risk of CAD in subjects with phenotype B may result, in
      part, from increased susceptibility to lipid peroxidative modification of LDL
      that is depleted in lipid contents, especially FC content per LDL particle.

PMID- 12200750
TI  - The effect of age, body mass index, and fasting triglyceride level on
      postprandial lipemia is dependent on apolipoprotein E polymorphism in subjects
      with non-insulin-dependent diabetes mellitus.
AB  - The aim of this study was to evaluate in non-insulin-dependent diabetes mellitus
      (NIDDM) subjects the respective influence of apolipoprotein (apo) E polymorphism,
      age, gender, weight, fasting triglyceride (TG) status, and glycemic status on
      postprandial lipemia. Apo E genotyping was performed in consecutive NIDDM
      hospitalized patients in order to recruite size-adjusted groups of each apo E
      genotype. In 57 NIDDM including 22 E3/3 (E3), 18 E2/3 (E2), and 17 E4/3 (E4)
      subjects, an 8-hour vitamin A-fat loading test was performed and TG and retinyl
      palmitate (RP) measured. Fasting TG level correlated with the TG area under the
      incremental curve (AUIC) (r = 0.512, P <.001) but not with RP AUIC. Despite not
      different fasting and postprandial TG concentrations, E2 and E4 carriers
      exhibited a 2- to 3-fold higher RP AUIC than E3 carriers (P =.01). Multivariate
      analysis indicated an age x apo E interaction on postprandial TG (P <.01), since
      the unfavorable effect of E2 and E4 allele on TG AUIC was unmasked by aging. In
      addition, a fasting TG x apo E interaction on postprandial TG was shown (P <.01),
      and the correlation between fasting TG and TG AUIC was actually restricted to E2
      or E4 carriers. Finally, the negative correlation between BMI and postprandial TG
      observed in the experimental group was actually restricted to E4 carriers (r = 
      0.77, P <.001). Our results indicate interactions between apo E polymorphism and
      aging, fasting TG level and BMI that may be important for analyzing postprandial
      TG clearance in NIDDM.

PMID- 12200751
TI  - Complete inhibition of hypothalamic somatostatin activity is only partially
      responsible for the growth hormone response to strenuous exercise.
AB  - The aim of this study was to investigate whether growth hormone (GH) release
      during strenuous exercise (EX) is due to complete inhibition of hypothalamic
      somatostatin (SS) activity. Eight healthy male subjects (age, 22.1 +/- 2.2 years;
      body mass index [BMI], 22.2 +/- 2.5 kg/m(2); maximum oxygen consumption
      [Vo(2)max], 52.2 +/- 1.5 mL/min/kg [mean +/- SD]) were exposed to strenuous EX on
      a cycle ergometer, with and without administration of pyridostigmine (PD), and to
      administration of PD alone. PD is an acetylcholine-esterase inhibitor that
      stimulates GH secretion by suppressing hypothalamic SS secretion and unmasking
      endogenous GH-releasing hormone (GHRH) tone. Serial blood samples in the fasted
      state were taken immediately before the start of each trial, and at appropriate
      intervals over 2 hours. GH responses were calculated as area under the response
      curve (AUC) by trapezoidal integration. The mean peak serum GH level to PD alone
      was 18.3 microg/L (range, 0.3 to 40.9), which was significantly lower than to EX
      alone: 64.1 microg/L (range, 30.5 to 90.5), and to the combined administration of
      PD and EX (PD+EX): 79.8 microg/L (range, 37.7 to 98.2) (P <.05). The arithmetic
      sum of the individual peak levels of 82.4 microg/L was not different from the
      mean peak level to PD+EX: 79.8 microg/L. AUC (mean +/- SEM) to PD alone (1,721 +/
      358 microg/L x 180 min) was not significantly different from that to EX alone
      (2,472 +/- 408 microg/L x 120 min), but was significantly lower than that to
      PD+EX: 3,526 +/- 752 (P <.05). Although the latter AUC was 6% smaller than the
      AUC obtained by arithmetic addition (3,747 +/- 706), this difference was not
      statistically significant. In conclusion, the additive effect between PD and EX
      indicates that PD and EX act independently in evoking GH responses to strenuous
      EX. Therefore, GH responses to strenuous EX are only partially due to complete
      inhibition of hypothalamic SS. Additional potentiating factors, such as
      activation of endogenous GHRH and ghrelin must be operative.

PMID- 12200752
TI  - Plasma kinetics of a chylomicron-like emulsion in normolipidemic obese women
      after a short-period weight loss by energy-restricted diet.
AB  - Chylomicrons carry dietary fats in the bloodstream for storage in body tissues,
      and thus play an important role in obesity. The 2-step chylomicron metabolism
      consists of lipolysis by lipoprotein lipase (LPL) on vessel walls and hepatic
      uptake of triglyceride-depleted remnants. A triglyceride-rich emulsion that
      mimics chylomicrons, labeled with [9,10-(3)H]glycerol-trioleate (TG) and [1
      (14)C] cholesteryl-oleate (CE) was intravenously injected into 14 obese women
      with body mass index between 30 and 40 kg/m(2) (age, 30 to 40 years), before and
      after a 2-month energy-restricted diet and into non-obese controls for
      determination of radioactive lipid plasma kinetics. TG kinetics evaluates
      lipolysis, whereas CE kinetics evaluates remnant removal. The emulsion TG
      fractional clearance rate (FCR, in min(-1)) was similar in obese women and their
      controls (0.126 +/- 0.065; controls, 0.111 +/- 0.031), but the CE-FCR was
      pronouncedly reduced in the obese subjects (0.028 +/- 0.014; controls, 0.070 +/-
      0.009 min(-1); P <.0001). After the energy-restricted diet, TG-FCR was reduced in
      the obese women (0.075 +/- 0.044 min(-1); P <.05), but CE-FCR was unchanged
      (0.032 +/- 0.025 min(-1)). Therefore, the lipolysis of the chylomicron-like
      emulsion is normal in obese women, but remnant removal from the plasma is
      diminished. After active weight loss by an energy-restricted diet, the remnant
      removal was unchanged but lipolysis was diminished, possibly due to adaptative
      changes in LPL activity.

PMID- 12200753
TI  - Evidence that tumor necrosis factor-alpha-induced hyperinsulinemia prevents
      decreases of circulating leptin during fasting in rats.
AB  - Administration of tumor necrosis factor-alpha (TNF-alpha) acutely increases
      leptin gene expression and circulating leptin concentrations in rodents and
      humans. Since TNF-alpha also induces hyperinsulinemia, and because insulin is a
      potent stimulator of leptin production, we hypothesized that elevated plasma
      insulin mediates TNF-alpha-induced increases of circulating leptin. To test this
      hypothesis, rats were made insulin-deficient with streptozotocin (STZ) and
      treated with subcutaneous implants that released insulin at a constant rate and
      thereby "clamped" insulin levels. STZ-diabetic and nondiabetic rats were injected
      with TNF-alpha or vehicle; plasma leptin, insulin, and glucose concentrations
      were measured during an initial 12-hour postinjection period of fasting and after
      a subsequent 12-hour period of refeeding. Food intake during the 12 hours after
      fasting was assessed as a physiologic correlate of changes in leptin
      concentrations. In nondiabetic rats, TNF-alpha increased plasma insulin (P =.016)
      and prevented the fasting-induced decrease of circulating leptin (P =.004) over
      the initial 12 hours compared with vehicle. Food intake during the refeeding
      period was 30% lower (P =.008) when the nondiabetic animals were injected with
      TNF-alpha. In contrast, TNF-alpha did not affect leptin concentrations in STZ
      diabetic animals with clamped plasma insulin levels or their food intake during
      the refeeding period. These results suggest that TNF-alpha-induced
      hyperinsulinemia likely mediates the stimulatory effect of TNF-alpha on
      circulating leptin in vivo. Elevated leptin levels may in turn contribute to the
      effect of TNF-alpha to decrease food intake.

PMID- 12200754
TI  - Glucagon dose-response curve for hepatic glucose production and glucose disposal
      in type 2 diabetic patients and normal individuals.
AB  - This study sought to examine whether enhanced hepatic sensitivity to glucagon
      contributes to impaired glucose homeostasis in subjects with type 2 diabetes
      mellitus (T2DM). Eight T2DM and 9 age-, weight-, and gender-matched nondiabetic
      subjects received a 4-hour glucagon infusion at the rates of 0.2, 0.5, 2, 6, and
      8 ng. kg(-1). min(-1) while maintaining the plasma insulin concentration constant
      at the basal level with exogenous infusions of somatostatin and insulin. On the
      evening prior to study, diabetic subjects received a low-dose insulin infusion at
      a rate designed to maintain euglycemia and this infusion rate was continued until
      the end of the glucagon infusion study on the following day. Each glucagon
      infusion study was performed on a separate day and in random order. 3-(3)H
      glucose was infused in all studies to measure endogenous glucose production (EGP)
      and the rate of whole body glucose disposal. During the first 2 hours (0 to 120
      minutes) of glucagon infusion, EGP increased sharply in both groups, and the
      initial rate of rise in EGP was higher in control versus diabetic subjects.
      During the last 2 hours (120 to 240 minutes) of glucagon infusion, EGP in the
      diabetics tended to be higher than controls during the 3 lower glucagon infusion
      rates and this difference reached statistical significance (P <.05 to.01) during
      the 6 and 8 ng. kg(-1). min(-1) infusions. During the 2 hours following cessation
      of glucagon (240- to 360-minute time period), the stimulation of glucose
      disappearance from plasma was impaired (P <.05) during all 5 glucagon infusion
      rates in the diabetics compared to controls. We conclude that in T2DM patients,
      the initial (0 to 120 minutes) stimulation of hepatic glucose output (which
      primarily reflects glycogenolysis) by glucagon is not enhanced in T2DM patients.
      The late (120 to 240 minutes) stimulation of hepatic glucose output (which
      primarily reflects gluconeogenesis) by glucagon tends to be increased, especially
      at supraphysiologic plasma glucagon concentrations.

PMID- 12200755
TI  - Extended-release niacin treatment of the atherogenic lipid profile and
      lipoprotein(a) in diabetes.
AB  - We tested the hypotheses that extended-release niacin is effective for the
      separate treatments of abnormalities in low-density liprotein (LDL) size, high
      density lipoprotein (HDL)-2, and lipoprotein(a) [Lp(a)] without potential
      negative effects on glycated hemoglobin levels. The lipids that constitute the
      atherogenic lipid profile (ALP), such as triglycerides, small, dense LDL
      cholesterol particle concentration, LDL particle size, total HDL-cholesterol
      (HDLc), HDL-2, and HDL-2 cholesterol concentration, as well as total LDL
      cholesterol (LDLc) and Lp(a), were measured in 36 diabetic patients with primary
      abnormalities of LDL particle size (n = 25), HDL-2 (n = 23), and/or Lp(a) (n =
      12) before and after extended-release niacin treatment. LDL particle size and HDL
      2 were measured using polyacrylamide gradient gel electrophoreses and Lp(a) was
      measured by enzyme-linked immunosorbent assay (ELISA). After extended-release
      niacin, LDL peak particle diameter increased from 25.2 +/- 0.6 nm to 26.1 +/- 0.7
      nm (P <.0001); small, dense LDLc concentration decreased from 30 +/- 17 mg/dL to
      17 +/- 10 mg/dL (P <.0001); total HDLc increased from 42 +/- 9 mg/dL to 57 +/- 16
      mg/dL (P <.0001); HDL-2 as the percent of total HDLc mass increased from 34% +/-
      10% to 51% +/- 17% (P <.0001); and Lp(a) decreased from 37 +/- 10 mg/dL to 23 +/-
      10 mg/dL (P <.001). Mean hemoglobin A(1c) level was improved during treatment
      from 7.5% +/- 1.6% to 6.5% +/- 0.9% (P <.0001). A subset of patients who had no
      change in hemoglobin A(1c) levels before and after treatment (6.8% +/- 1% v 6.7%
      +/- 1%; not significant) showed identical lipid changes. Twenty-two percent of
      patients were unable to tolerate extended-release niacin due to reversible side
      effects. These data indicate that in diabetic patients, extended-release niacin
      (1) is effective for separately treating diabetic dyslipidemias associated with
      abnormal LDL size, HDL-2, and Lp(a) independently of glycated hemoglobin levels;
      (2) must be used with modern and aggressive oral hypoglycemic agents or insulin
      treatment; and (3) is a major drug for the treatment of diabetic dyslipidemias
      because of its broad spectrum of effectiveness for the ALP and Lp(a).

PMID- 12200756
TI  - Autoregulation of endogenous glucose production during hyperglucagonemia.
AB  - Increased endogenous glucose production (EGP) contributes to fasting
      hyperglycemia in type II diabetes. In nondiabetic subjects, increased
      gluconeogenesis from lactate does not increase EGP. Type 2 diabetes is associated
      with hyperglucagonemia. The present study was undertaken to examine whether
      physiologic elevation of plasma glucagon overrides autoregulation of EGP. Eight
      healthy volunteers were studied on 2 occasions, once during a 3-hour infusion of
      30 micromol/kg/min Na-lactate and once during a control infusion of Na
      bicarbonate. Plasma glucagon, insulin, and growth hormone were clamped at
      identical levels in both experiments. Rates of appearance of glucose, lactate,
      and gluconeogenesis from lactate were measured by tracer techniques. Glucagon
      infusion rate was elevated when the lactate or bicarbonate infusions were started
      to induce physiologic hyperglucagonemia. Plasma glucagon increased from baseline
      levels (234 +/- 21 ng/L and 211 +/- 23 ng/L) to 313 +/- 47 ng/L (bicarbonate
      experiments) and 329 +/- 43 ng/L (lactate experiments, means +/- SE, P >.3).
      Lactate infusion increased plasma lactate concentrations from 1.1 +/- 0.9 to 4.6
      +/- 0.5 mmol/L (P =.0003). Lactate conversion to glucose increased from 1.5+/-0.3
      to 2.8+/-0.8 micromol/kg/min (P =.03) and from 1.7 +/- 0.3 to 8.1 +/- 0.8
      micromol/kg/min (P =.0003) in the bicarbonate and lactate experiments,
      respectively. The increments in lactate conversion to glucose differed
      significantly (P =.0008). Nevertheless, plasma glucose and EGP were not different
      in the bicarbonate and lactate experiments: 5.4 +/- 0.5 versus 6.6 +/- 0.7 mmol/L
      (P =.21), and 10.5 +/- 0.6 versus 11.6 +/- 0.6 micromol/kg/min (P =.19). We
      conclude that in normal volunteers, neither hyperglucagonemia nor the combination
      of hyperglucagonemia and increased substrate availability alters the
      autoregulation of EGP.

PMID- 12200757
TI  - Glycoxidized low-density lipoprotein enhances monocyte chemoattractant protein-1
      mRNA expression in human umbilical vein endothelial cells: relation to
      lysophosphatidylcholine contents and inhibition by nitric oxide donor.
AB  - Low-density lipoprotein (LDL) may undergo more glycation or oxidation in patients
      with diabetes mellitus than in nondiabetic subjects. We investigated whether
      glycoxidized LDL (goLDL) induces monocyte chemoattractant protein-1 (MCP-1) mRNA
      expression through activation of nuclear factor-kappaB (NFkappaB), and determined
      the effect of nitric oxide (NO) on MCP-1 mRNA expression in human umbilical vein
      endothelial cells (HUVEC). Oxidized (oxLDL) or goLDL enhanced MCP-1 mRNA
      expression in HUVEC, and preincubation with NOR3, a NO donor, abrogated such
      stimulation. goLDL increased NFkappaB-DNA binding activity in HUVEC and this
      effect was also suppressed by NOR3. We measured lysophosphatidylcholine (lyso-PC)
      contents in modified LDL using electrospray ionization liquid chromatography/mass
      spectrometry (LC/MS) to identify its molecular species. MCP-1 mRNA expression and
      NFkappaB activation correlated significantly with palmitoyl- and stearoyl-lyso-PC
      contents in LDL. Our results suggest that LDL modified by glycation and oxidation
      may contribute to the development of accelerated atherosclerosis in the presence
      of diabetes, a process that may be prevented by increased vascular NO
      availability.

PMID- 12200758
TI  - Increased rates of lipolysis among human immunodeficiency virus-infected men
      receiving highly active antiretroviral therapy.
AB  - Human immunodeficiency virus (HIV) lipodystrophy is associated with fat
      redistribution, dyslipidemia, and insulin resistance; however, the mechanism of
      insulin resistance remains unknown. We hypothesized that HIV-infected subjects
      with fat redistribution have increased rates of lipolysis and increased
      circulating free fatty acid (FFA) levels that contribute to insulin resistance.
      Anthrompometric and body composition data were obtained and a standard 75-g oral
      glucose tolerance test (OGTT) was performed on day 1 of the study. Stable isotope
      infusions of glycerol and palmitate were completed following an overnight fast to
      assess rates of lipolysis and FFA flux in HIV-infected men (n = 19) with and
      without fat redistribution and healthy controls (n = 8) on day 2. Total FFA
      levels after standard glucose challenge were increased among HIV-infected
      subjects and positively associated with abdominal visceral adipose tissue area.
      In contrast, fasting total FFA levels were inversely associated with subcutaneous
      fat area. Rates of basal lipolysis were significantly increased among HIV
      infected subjects (rate of appearance [Ra] glycerol, 4.1 +/- 0.2 v 3.3 +/- 0.2
      micromol/kg/min in controls; P =.02). Among HIV-infected subjects, use of
      stavudine (P =.006) and the rate of lipolysis (ie, Ra glycerol, P =.02) were
      strong positive predictors of insulin resistance as measured by insulin response
      to glucose challenge, controlling for effects of age, body mass index (BMI),
      waist-to-hip ratio (WHR), and protease inhibitor (PI) exposure. These data
      demonstrate increased rates of lipolysis and increased total FFA levels in HIV
      infected subjects and suggest that increased lipolysis may contribute to insulin
      resistance in this patient population.

PMID- 12200759
TI  - Anticardiolipin antibodies in children with insulin-dependent diabetes mellitus.
AB  - Insulin-dependent diabetes mellitus (IDDM) is an autoimmune disease that
      selectively destroys insulin-secreting pancreatic beta cells. Anticardiolipin
      antibody is an autoantibody directed against cell membranes. An association of
      this antibody with diabetes mellitus has not been widely reported. The current
      investigation was performed to determine the prevalence of IgG and IgM
      anticardiolipin antibodies in 2 groups of children with type 1 IDDM and to find a
      relation, if any, with the control and duration of the disease. The study
      included 30 children with type 1 IDDM and 20 healthy control children. The
      children were subjected to history taking, clinical examination, and laboratory
      estimation of anticardiolipin IgG and IgM antibodies and glycosylated hemoglobin
      (HbA(1c)). Analysis of the results showed that the mean levels of serum
      anticardiolipin IgG and IgM antibodies were significantly higher among the
      diabetic children than the healthy controls. Mean values of serum anticardiolipin
      IgG and IgM antibody levels were significantly higher in children with recent
      onset diabetes (29.90 +/- 12.60 GPL/mL and 12.825 +/- 3.762 MPL/mL) than in those
      of long duration (>1 year: 10.84 +/- 5.796 GPL/mL and 4.142 +/- 2.910 MPL/mL,
      respectively). A negative correlation between the duration of diabetes and the
      level of IgG and IgM anticardiolipin antibodies and a positive correlation
      between the level of IgG and the level of IgM antibodies were observed. However,
      there was a nonsignificant correlation between anticardiolipin IgG and IgM levels
      and HbA(1c) levels, insulin dose, and fasting blood sugar. Therefore,
      anticardiolipin antibodies should be added to the list of autoantibodies detected
      in IDDM especially in the early stage of the disease.

PMID- 12200760
TI  - The effects of lovastatin on proteasome activities in highly purified rabbit 20 S
      proteasome preparations and mouse MC3T3-E1 osteoblastic cells.
AB  - A number of clinical studies suggest that the use of the lipid-lowering agents
      collectively referred to as statins (hydroxymethyl glutaryl coenzyme A [HMG-CoA]
      reductase inhibitors) is associated with increased bone density, reduced fracture
      risk, and net bone anabolism. Statins (< or =5 micromol/L) stimulate rodent bone
      formation, but the mechanistic basis remains unclear. Since statins and the
      proteasome inhibitor lactacystin are structurally similar, and high doses (> or
      =40 micromol/L) of statins can inhibit the chymotryptic activity of the
      proteasome, it has been hypothesized that statins exert their anabolic effects on
      bone, in part, by inhibiting the proteasome, the major eukaryotic intracellular
      regulatory protease. This hypothesis conflicts with reports that statins
      stimulate proteasome activity and that proteasome-catalyzed degradation of
      specific substrates is required for cell proliferation, differentiation, and
      survival. Our chief objective was to determine the effects of statins (< or =10
      micromol/L) on the chymotryptic activity of the proteasome in the 20 S proteasome
      and intact murine MC3T3-E1 cells cultured to low density (preosteoblasts) or high
      density (differentiated osteoblasts). Lovastatin (0.001 micromol/L to 5.0
      micromol/L) stimulated the chymotryptic activity of the highly purified 20 S
      proteasome. Preosteoblasts and differentiated osteoblasts treated with 1, 5, or
      10 micromol/L lovastatin for 1 hour exhibited morphologic abnormalities that were
      ameliorated by preincubation and treatment with 20 micromol/L mevalonate. The
      chymotryptic activity of the preosteoblast proteasome increased after 2 days of
      1.0 micromol/L or 5.0 micromol/L lovastatin treatment. In addition, the DNA and
      protein contents of 1.0 micromol/L or 5.0 micromol/L lovastatin-treated
      preosteoblast cultures were lower those that observed in vehicle-, 0.01
      micromol/L lovastatin-, or 0.10 micromol/L lovastatin-treated cultures. The
      chymotryptic activity of the proteasome was much lower in differentiated
      osteoblasts than in preosteoblasts. Two days of treatment with 1 micromol/L
      lovastatin modestly stimulated the chymotryptic activity of the proteasome in
      differentiated osteoblasts, but had no effects on total protein or DNA, compared
      to cultures treated with vehicle or lower doses of lovastatin. Thus, the data
      support the hypothesis that statins stimulate proteasome activities in highly
      purified proteasome preparations and preosteoblastic cells. Treating
      preosteoblastic or differentiated MC3T3-E1 cells with lovastatin concentrations >
      or = 1 micromol/L resulted in abnormal morphology and reduced the DNA and protein
      levels in preosteoblastic cultures, confirming the adverse effects of statins
      previously reported for other cells. In conclusion, the hypothesis that
      lovastatin exerts its anabolic effects on bone by inhibiting the proteasome
      activity of the osteoblast was refuted, and the effects of lovastatin on MC3T3-E1
      cells were found to be highly dose- and development-dependent.

PMID- 12200761
TI  - Beta-cell dysfunction in late-onset diabetic subjects carrying homozygous
      mutation in transcription factors NeuroD1 and Pax4.
AB  - Polymorphisms in beta-cell transcription factor genes, Ala45Thr in the NeuroD1
      gene and Arg121Trp in the Pax4 gene, have been reported. To clarify the role of
      these mutations in the pathogenesis of late-onset diabetes, we examined the
      insulin secretion and sensitivity in diabetic patients carrying the homozygous
      mutation in the NeuroD1 gene or Pax4 gene. We screened for the polymorphisms in
      NeuroD1 and Pax4 genes in 296 late-onset diabetic patients and 177 unrelated
      control subjects over 60 years of age. Genotyping was performed by polymerase
      chain reaction-restriction fragment length polymorphism (PCR-RFLP) followed by
      direct sequencing. Acute insulin secretion was evaluated using a 2-compartment
      model analysis of C-peptide kinetics after intravenous glucose load (CS1).
      Insulin sensitivity was estimated by the insulin-modified minimal model analysis
      (Si). Four diabetic patients carried the homozygous mutation (Thr/Thr) in the
      NeuroD1 gene and 3 patients carried the homozygous mutation (Trp/Trp) in the Pax4
      gene, while both homozygous mutations were not detected in the control subjects.
      In patients A, B, C, and D with homozygous mutations in NeuroD1, CS1 (normal
      range, 6.8 to 18.5 ng/mL/min) was 0.508, 1.481, 1.223, and 1.584 ng/mL/min,
      respectively, and Si (normal range, 2.6 to 7.6 x 10(-4)/min/[microU/mL]) was
      0.727, 3.31, 3.79, and 0.00 x 10(-4)/min/(microU/mL), respectively. In patients
      X, Y, and Z with homozygous mutation in Pax4, CS was 0.418, 0.208, and 1.279
      ng/mL/min, respectively, and Si was 1.11, 2.88, and 0.00 x 10(
      4)/min/(microU/mL), respectively. Since acute insulin secretion in response to
      glucose was markedly impaired and insulin resistance was varied in the patients
      carrying the homozygous mutations in the NeuroD1 and Pax4 genes, the mutations
      are ones of the factors involved in the beta-cell dysfunction and do not relate
      to the insulin resistance. These homozygous mutations appear to play a part in
      the pathogenesis of beta-cell defect in about 2.5% of Japanese patients with late
      onset diabetes.

PMID- 12200762
TI  - Fiber-multivitamin combination therapy: a beneficial influence on low-density
      lipoprotein and homocysteine.
AB  - Proven effective alternative and adjunctive therapies for lipid lowering could be
      beneficial for patients with hyperlipidemia. We evaluated a 90% soluble fiber for
      its ability to alter lipid, lipoprotein, and homocysteine levels in the setting
      of coadministered folate and B vitamins. Patients (n = 119) were randomized to
      either the fiber and vitamin combination, or placebo. Fasting lipid, glucose, and
      homocysteine concentrations, and body mass index (BMI) were obtained at baseline
      and weeks 4 and 8. Both between-group (Wilcoxon rank-sum test) and within-group
      (paired t test) comparisons were used to evaluate treatment effects. After 6
      weeks of a diet therapy (National Cholesterol Education Program [NECP] Step I)
      run-in period, subjects in both groups had similar low-density lipoprotein
      cholesterol (LDL-C) levels (159 mg/dL v 158 mg/dL). The treated group showed a
      7.1% +/- 11.6% reduction by 4 weeks, which was maintained at 8 weeks (7.9% +/-
      11.0%). Placebo patients had a slight increase in LDL-C values over the same
      period (+2.4% +/- 11.7%), for a 10.3% difference between groups. The treatment
      effect was statistically significant both between groups (P <.001) and within the
      active-treatment group (P <.001) after the 8-week intervention. Apolipoprotein B
      (ApoB) levels in a representative subset of the treated group (n = 53) decreased
      by 20% (P =.004). The fiber blend neither raised triacylglycerol (TG) (P =.95)
      nor lowered high-density lipoprotein cholesterol (HDL-C) levels (P =.54), and
      lowered homocysteine (active, 9.8 to 8.7/micromol/L, P =.02; placebo, 9.4 to 9.2
      /micromol/L, P =.98). Thus, a significant LDL-C lowering effect, with parallel
      Apo B reduction, was demonstrated for this fiber/vitamin combination. No adverse
      changes on TG or HDL-C levels were noted, and folate/B vitamin benefits
      attributed to homocysteine reduction were preserved. Concurrent administration of
      fiber and vitamins represents a preventive approach that may reduce the need for
      concomitant lipid-lowering therapies or serve as an adjunct therapy.

PMID- 12200763
TI  - Insulin and insulin-like growth factor-1 action on human skeletal muscle:
      preferential effects of insulin-like growth factor-1 in type 2 diabetic subjects.
AB  - The metabolic actions of insulin and insulin-like growth factor-1 (IGF-1) were
      compared in cultured skeletal muscle cells from nondiabetic (ND) and type 2
      diabetic subjects. Insulin stimulated glucose uptake with comparable sensitivity
      in ND (EC(50) = 2.0 +/- 0.7 nmol/L) and diabetic (1.3 +/- 0.4) cells. IGF-1
      sensitivity for uptake stimulation was similar in ND (EC(50) = 0.30 +/- 0.06
      nmol/L) and type 2 cells (0.37 +/- 0.01). In ND cells, insulin and IGF-1 were
      equally potent for stimulation of glucose uptake and glycogen synthase (GS)
      activity. However, in diabetic cells, maximal insulin stimulation of both
      responses was only half of the increases due to IGF-1. Final absolute activities
      after IGF-1 stimulation were still lower in diabetic cells compared with cells
      from ND subjects. Hormonal stimulation of Akt phosphorylation exhibited the same
      behavior as metabolic responses; comparable for insulin and IGF-1 in ND muscle,
      while IGF-1 was significantly more effective in diabetic cells. Both insulin
      receptor (IR) binding and receptor protein expression were similar in ND and
      diabetic cells. IGF-1 binding and receptor protein expression were not
      significantly different in diabetic compared with ND cells. The expression of IGF
      binding proteins (IGFBP) 3, 5, and 6 were similar in ND and diabetic cells; IGFBP
      4 was slightly, but significantly higher, in diabetic cells. While insulin and
      IGF-1 are equally effective on metabolic responses in ND muscle, diabetic muscle
      cells are markedly more resistant to insulin than IGF-1. The greater metabolic
      activity of IGF-1 in type 2 diabetic muscle may provide new insights into the
      mechanisms of insulin resistance in skeletal muscle.

PMID- 12200764
TI  - Case report: somatostatin producing teratoma, causing rapidly alternating extreme
      hyperglycemia and hypoglycemia, and ovarian somatostatinoma.
AB  - A 54-year-old woman presented with extremely fluctuating and symptomatic blood
      glucose levels. Very high levels of somatostatin and low levels of insulin, C
      peptide, gastric inhibitory peptide (GIP), and glucagon-like peptide-1 (GLP-1) in
      peripheral blood were constantly present. A benign somatostatinoma was localized
      by meta-iodobenzyl guanidine iodine 123 (MIBG-I(123)) scintigraphy and
      successfully removed encapsulated in an ovarian teratoma. The patient made a
      complete recovery. The case described is unique with regard to clinical
      symptomatology and anatomic localization of the tumor.

PMID- 12200765
TI  - Glucose dependency of arginine vasopressin-induced insulin and glucagon release
      from the perfused rat pancreas.
AB  - The purpose of this study was to investigate the glucose dependency of arginine
      vasopressin (AVP)-induced insulin, glucagon, and somatostatin release from the
      perfused rat pancreas. AVP (30 or 300 pmol/L) was tested in the presence of a
      glucose concentration of 0, 1.4, 5.5 (basal level), or 20 mmol/L. The rates of
      insulin release at 0 and 1.4 mmol/L glucose were approximately 70% to 80% and 60%
      to 70% less, respectively, than that at the baseline level. AVP (30 or 300
      pmol/L) failed to change insulin release at 0 and 1.4 mmol/L glucose. At the
      basal glucose level, AVP (300 pmol/L) induced a biphasic insulin release, a peak
      followed by a sustained phase. In addition, the combination of glucose (20
      mmol/L) and AVP (300 pmol/L) induced a higher insulin peak and sustained phase
      than 20 mmol/L glucose alone. The rates of glucagon release at 0 and 1.4 mmol/L
      glucose were about 3- and 2-fold more, respectively, than that at the baseline
      level. At 0 and 1.4 mmol/L glucose, both 30 and 300 pmol/L AVP caused a higher
      glucagon peak and sustained phase than 0 and 1.4 mmol/L glucose alone. At the
      basal glucose level, AVP (30 or 300 pmol/L) induced a biphasic glucagon release,
      a peak followed by a sustained phase. The rate of glucagon release at 20 mmol/L
      glucose was approximately 60% to 70% less than that at the baseline level. When
      AVP (300 pmol/L) was administered in 20 mmol/L glucose, it induced a transient
      glucagon peak, which was 2.4-fold of the baseline level. At all glucose
      concentrations tested, AVP (30 or 300 pmol/L) failed to change somatostatin
      release. These results suggested that (1) hypoglycemia directly increases
      glucagon and decreases insulin release; (2) AVP induces insulin and glucagon
      release by a direct action on beta and alpha cells, respectively; (3) AVP induces
      insulin and glucagon release in a glucose-dependent manner-the higher the glucose
      concentration, the greater the enhancement of AVP-induced insulin release,
      whereas the lower the glucose concentration, the higher the enhancement of AVP
      induced glucagon release; and (4) alpha cells are more sensitive to AVP than beta
      cells in hormone release.

PMID- 12200766
TI  - mRNA expression of enzymes involved in taurine biosynthesis in rat adipose
      tissues.
AB  - mRNA levels of the enzymes involved in taurine synthesis were compared among 12
      rat tissues. Using a quantitative reverse transcription-polymerase chain reaction
      (RT-PCR) and Northern-blotting, high levels of mRNA for cysteine dioxygenase were
      confirmed in the liver and kidney. Unexpectedly, the mRNA levels in epididymal
      and perirenal white adipose tissues and interscapular brown adipose tissue were
      remarkably high, at least compared with those observed in the liver and kidney.
      Cysteine dioxygenase mRNA levels in other tissues were very low. Using Northern
      blotting, significant amounts of cysteine sulfinic acid decarboxylase mRNA were
      detected in the liver, kidney, epididymal and perirenal white adipose tissues,
      and brown adipose tissue, but not in other tissues. Again, the mRNA levels of
      cysteine sulfinic acid decarboxylase in adipose tissues were comparable to or
      even higher than those in the liver and kidney. The activity of cysteine sulfinic
      acid decarboxylase in white and brown adipose tissues was 50% to 80% of that in
      the liver and much higher than the values observed in kidney, lung, and brain.
      However, the occurrence of cysteine dioxygenase activity in adipose tissues was
      not confirmed.

PMID- 12200767
TI  - Determination of skeletal muscle triglyceride synthesis using a single muscle
      biopsy.
AB  - A novel stable isotopic technique for the determination of triglyceride synthesis
      in skeletal muscle by using a single muscle biopsy has been developed and
      evaluated in rats. In previous studies using (13)C-tracers, muscle triglyceride
      synthesis is usually determined using at least 2 biopsies, the first of which
      serves as the baseline sample for the measurement of natural (13)C abundance. In
      the present studies, the baseline biopsy has been eliminated by making the use of
      the isotopic information of a nontraced fatty acid in the muscle triglyceride
      pool. This is based on the fact that the source and, hence, the natural (13)C
      abundance of fatty acids in the same triglyceride pool is similar. To demonstrate
      and validate the method, a series of rat studies have been conducted to have
      established that (1) the natural (13)C abundance of 4 major fatty acids in the
      muscle triglyceride pool is similar; (2) there are no (13)C-label exchanges
      between fatty acids in the lipid pool; and (3) the incorporation of (13)C
      palmitate into muscle triglycerides determined using this technique favorably
      compared with that determined by the traditional method. This approach makes
      stable isotope studies possible in which more than 1 muscle biopsy is difficult
      or impossible. Therefore, it has the potential to facilitate investigation of
      triglyceride metabolism in the skeletal muscle.

PMID- 12200768
TI  - Adipose tissue compartments and the kinetics of very-low-density lipoprotein
      apolipoprotein B-100 in non-obese men.
AB  - We examined the association between the kinetics of very-low-density lipoprotein
      (VLDL) apolipoprotein B-100 (apoB) and intraperitoneal, retroperitoneal,
      subcutaneous abdominal, and total adipose tissue masses (IPATM, RPATM, SAATM,
      TATM, respectively) in 14 healthy, non-obese men (body mass index [BMI] < 30
      kg/m(2)). Hepatic secretion of VLDL-apoB was measured using an intravenous
      infusion of 1-[(13)C]-leucine. Isotopic enrichment of VLDL-apoB was measured
      using gas chromatography-mass-spectrometry and a multicompartmental model
      (Simulation, Analysis, and Modeling Software [SAAM II]) used to estimate the
      fractional catabolic rate (FCR) of VLDL-apoB. IPATM, RPATM, and SAATM (kg) were
      quantified between T11 and S1 using magnetic resonance imaging (MRI); TATM (kg)
      was determined using bioelectrical impedance. Insulin resistance was estimated by
      homeostasis model assessment (HOMA) score. In stepwise regression analysis, IPATM
      was the best predictor of the hepatic secretion of VLDL-apoB (r =.58, P <.05) and
      TATM the best predictor of the FCR of VLDL-apoB (r = -.56, P <.05). After
      adjusting for TATM, IPATM explained 59% of the variance in VLDL apoB secretion (P
      =.03). None of the fat compartments were significantly associated with VLDL-apoB
      kinetics after adjusting for HOMA score. The findings suggest that in non-obese
      men the quantity of both intraperitoneal and total fat are significant predictors
      for the kinetics of VLDL-apoB, which in turn, determines plasma triglyceride
      concentrations; these associations may, in part, be mediated by variations in
      insulin resistance, particularly among individual who are not ostensibly obese.
      Our preliminary results need confirmation in a larger study.

PMID- 12200769
TI  - Comparison of human abdominal subcutaneous versus omental preadipocyte
      differentiation in primary culture.
AB  - Excess intra-abdominal fat is associated with a higher risk for type 2 diabetes
      mellitus and cardiovascular disease, yet little is known about what influences
      regional adipose tissue accumulation. Adipocytes arise from specialized
      fibroblast-like preadipocytes within the adipose tissue stromal-vascular
      compartment. The aim of our study was to determine if there are variations in
      preadipocyte differentiation between abdominal subcutaneous (SC) and omental (OM)
      preadipocytes. Abdominal SC and OM preadipocytes were isolated from adipose
      tissue obtained from 18 subjects (7 men, 11 women), undergoing elective abdominal
      surgery, by collagenase treatment and filtration/centrifugation. Preadipocytes
      were placed in culture and then differentiated for 3 weeks in a serum-free medium
      containing insulin, dexamethasone, isobutylmethylxanthine, and carbaprostacyclin.
      The cells were then harvested for measurement of cytosolic glycerol phosphate
      dehydrogenase (GPDH), a marker of terminal differentiation. Data are expressed as
      a differentiation index (DI), which was the log of the SC/OM ratio of GPDH values
      for each patient (calculated as 0 for an equivalent SC v OM responses). The mean
      DI for the group (n = 18) was 0.04, with a 95% confidence interval (CI) of -0.11
      to 0.20. The mean DI for men was 0.07 (95% CI, -0.06 to 0.19), and that for women
      was 0.03 (95% CI, -0.21 to 0.27). This indicates that SC versus OM preadipocyte
      differentiation responses were not significantly different from each other,
      either for the group as a whole or when divided by gender. Overall, 8 subjects
      had a DI favoring SC preadipocyte differentiation, compared to 11 subjects with a
      DI reflecting greater OM preadipocyte differentiation. There was no correlation
      of the DI with body mass index or age. Our results indicate that preadipocytes
      from the abdominal SC adipose tissue depot do not uniformly differentiate more
      than those from the OM depot.

PMID- 12200770
TI  - Effects of two oral contraceptives on plasma levels of nitric oxide,
      homocysteine, and lipid metabolism.
AB  - This prospective study was performed to investigate the effect of 2 low-dose oral
      contraceptives containing a second- and a third-generation progestagen on
      factors, which may influence the individual cardiovascular risk by regulating
      endothelial function and development of atherosclerosis. Sixteen women were
      randomized to receive 3 cycles of treatment with 30 microg ethinylestradiol/150
      microg levonorgestrel (EE/LNG) and 3 cycles of treatment with 30 microg
      ethinylestradiol/75 microg gestodene (EE/GSD). Before and after treatment the
      plasma levels of nitric oxide (NO), homocysteine, cholesterol, high-density
      lipoprotein (HDL), and triglycerides were measured. No significant alterations of
      the NO, homocysteine, and triglyceride plasma levels were observed during use of
      both contraceptive pills. Compared to levels after EE/LNG treatment, HDL plasma
      levels were higher (P =.05) and the cholesterol/HDL ratio was lower after the
      EE/GSD pill (P =.05). Significant correlations were found between NO and
      homocysteine and NO and cholesterol. Our data indicate that the cardiovascular
      risk associated with these contraceptive pills may not be explained by a negative
      influence on NO or homocysteine.

PMID- 12200772
TI  - Liver transplantation in association with hepatocellular carcinoma: an update of
      the International Tumor Registry.
AB  - Hepatocellular carcinoma is an epithelial tumor derived from hepatocytes that
      accounts for more than 80% of all primary hepatic tumors. The severity of the
      underlying disease is almost always the key factor in deciding whether to
      consider liver resection or transplantation as its treatment. Data in our
      registry corresponding to almost 800 patients from transplant centers throughout
      the world showed that patient survival after liver transplantation was
      significantly affected by histologic grade, tumor size >5 cm, and the presence of
      positive nodes. Recurrence-free survival showed a correlation with tumor size >5
      cm, positive nodes, bilobar spread, and vascular invasion. At the present time,
      59% of patients in our registry are alive, 84% of whom are free of tumor. Of
      those who died, half did so without evidence of tumor.

PMID- 12200773
TI  - Focal lesions in cirrhotic explant livers: pathological evaluation and accuracy
      of pretransplantation imaging examinations.
AB  - Imaging detection and diagnosis of hepatocellular carcinomas (HCCs) and
      dysplastic nodules (DNs) in cirrhotic patients is important because the number,
      size, and type of focal lesions strongly influence patient management. Focal
      lesions detected by imaging examinations during pretransplantation evaluation
      were correlated with focal lesions detected during detailed pathological
      examination of 49 cirrhotic explant livers. Within 6 months before
      transplantation, color Doppler ultrasonography (US), contrast-enhanced computed
      tomography (CT), and magnetic resonance (MR) imaging were performed in 94%, 33%,
      and 55% of patients, respectively. In 2% to 8% of patients, different types of
      benign focal lesions were present, and a considerable proportion was interpreted
      as (pre)malignant on imaging examination. US detected only the largest HCCs
      (patient sensitivity, 40%; specificity, 100%) and no DNs. On a per-patient basis,
      contrast-enhanced CT and MR imaging had poor sensitivity (20% and 27%,
      respectively) and good specificity (100% and 94%, respectively) for DNs. Patient
      sensitivity and specificity of both techniques for HCC were reasonable (50% for
      CT, 70% for MR imaging) and good (79% for CT, 82% for MR imaging), respectively.
      Neither technique was able to detect smaller (pre)malignant lesions. As a
      consequence, 10% of patients underwent transplantation, although they exceeded
      the tumor number limit. Currently used imaging techniques cannot correctly
      determine the exact tumor burden in some cirrhotic patients. Regular contrast
      enhanced MR examination of cirrhotic patients waiting for liver transplantation
      is the best tool for the early detection of (pre)malignant lesions.

PMID- 12200774
TI  - Diagnosing hepatocellular carcinoma: a virtual reality.

PMID- 12200775
TI  - Liver transplantation for hepatocellular carcinoma: comparison of the proposed
      UCSF criteria with the Milan criteria and the Pittsburgh modified TNM criteria.
AB  - We previously proposed modified staging criteria for predicting acceptable
      outcome after orthotopic liver transplantation (OLT) for hepatocellular carcinoma
      (HCC). These were solitary tumor < or = 6.5 cm, or three or fewer nodules with
      the largest lesion < or = 4.5 cm and total tumor diameter < or = 8 cm, without
      gross vascular invasion (University of California, San Francisco [UCSF]
      criteria). In this study, we further evaluated the performance of the Milan
      criteria (solitary tumor < or = 5 cm, or three or fewer lesions none > 3 cm), the
      UCSF criteria, and the Pittsburgh modified tumor-node-metastasis (TNM) criteria.
      Pathologic HCC staging according to each set of criteria was performed in 70
      patients. The difference in survival when comparing 24 patients with HCC
      exceeding Milan criteria versus 46 patients meeting Milan criteria did not reach
      statistical significance (HR, 2.0; P = .12). Using our definition for acceptable
      2-year survival to be > or = 70%, the 14 patients (20%) meeting UCSF criteria but
      exceeding Milan criteria had a 2-year survival of 86% (95% CI, 54% to 96%).
      Survival for Pittsburgh stage I, II, and IIIA patients as a group was
      significantly better than for stages IIIB and IVA patients combined (HR, 4.2; P =
      .007), and similar to survival for patients meeting UCSF criteria. Advanced tumor
      exceeding UCSF criteria served reasonably well as a surrogate marker for poorly
      differentiated grade and microvascular invasion. In conclusion, our analyses
      suggest that UCSF criteria better predict acceptable posttransplant outcome than
      Milan criteria. UCSF criteria confer a different advantage over Pittsburgh
      criteria, which require information on microvascular invasion that is difficult
      to ascertain preoperatively without the attendant risk of biopsy.

PMID- 12200776
TI  - The quandary over liver transplantation for hepatocellular carcinoma: the greater
      sin?

PMID- 12200777
TI  - Liver transplantation for patients on methadone maintenance.
AB  - Most transplant programs require abstinence of at least 6 months from alcohol and
      illicit drugs before orthotopic liver transplantation (OLT). However, there are
      no published data regarding OLT outcomes in patients who are currently on
      methadone maintenance treatment (MMT) as part of the treatment of their heroin
      addiction at the time of OLT. The objective of this study is to evaluate our
      experience regarding the outcome of OLT in patients with end-stage liver disease
      (ESLD) who were on MMT at the time of OLT. Between March 1993 and May 1999, a
      total of 185 patients with ESLD underwent OLT at our center. Five transplant
      recipients (2.7%) had a history of heroin abuse and had undergone drug and
      alcohol rehabilitation, but could not be weaned off methadone. Pre-OLT status,
      drug history, perioperative course, compliance with medical therapy, post-OLT
      follow-up, and patient and allograft survival were analyzed in detail in these
      patients. All patients on MMT underwent uneventful OLTs. Their compliance with
      medications and follow-up was excellent. One patient was weaned completely off
      methadone after OLT. Post-OLT mean hospital stay in this group was 43 +/- 25
      days. Although the number of patients was small, long-term outcome of liver
      transplant recipients on MMT appears similar to that of patients not on MMT who
      underwent OLT during this period. Our results suggest cirrhotic patients on MMT
      should be considered for OLT if they meet the same psychosocial requirements as
      patients with alcohol abuse. Furthermore, it is not necessary for patients to be
      weaned off methadone before OLT.

PMID- 12200778
TI  - Methadone is a medication, not an addiction.

PMID- 12200779
TI  - Long-term follow-up of survival of liver transplant recipients with familial
      amyloid polyneuropathy (Portuguese type).
AB  - Portuguese type familial amyloid polyneuropathy is a dominantly inherited
      neuropathic amyloidosis caused by a mutant transthyretin (TTR). Because TTR is
      produced mainly by the liver, liver transplantation (LT) abolishes production of
      the amyloidogenic variant TTR. To date, the procedure appears to halt the
      progress of the disease. However, long-term outcome is unknown. The aim of the
      present study is to evaluate the survival of our initial group of unselected
      liver transplant recipients with FAP. Seventy patients, 51 transplant recipients
      and a control group of 19 nontransplantation patients, with disease onset before
      the age of 55 years were included on the study. Transplant recipients were
      divided into two categories: (1) early series, with patients followed up for 5
      years or longer, and (2) new series, with patients followed up for 1 to 5 years.
      Nonparametric statistical methods were used. Binary regression analyses were
      performed by stepwise logistic regression and Cox proportional hazard regression.
      Survival analysis was performed using Kaplan-Meier analysis, the Cox-Mantel test.
      Survival analyses and Cox proportional hazard regression analysis were performed
      from disease onset, not from LT. Significantly decreased survival was noted for
      transplant recipients with a modified body mass index (mBMI) less than 600
      compared with the control group (P < .05). A significant difference in survival
      also was observed between transplant recipients with an mBMI greater than 600 at
      the time of LT compared with those with an mBMI less than 600 (P < .02). mBMI and
      age at LT had a significant impact on survival; whereas late deaths were related
      to age at LT, early deaths were related to mBMI. The cumulative 10-year survival
      rate after disease onset was 94% in the new series, with one early death (< 6
      months) after LT, compared with a 78% survival rate and eight early deaths in the
      early series (P = .1).

PMID- 12200780
TI  - Is MELD really the definitive score for liver allocation?
AB  - The best system for organ allocation is still a controversial issue. The aim of
      this study was to study the accuracy of four different scores to predict
      mortality on the waiting list and, thus, their usefulness to determine organ
      allocation. We retrospectively compared two groups of patients, those who died on
      waiting list (group D) and those who successfully underwent transplantation
      (group T) during the same time period. Four scores, at the time of entering the
      waiting list and just before liver transplantation or death, were evaluated. The
      evaluated scores were as follows: (1) the Child-Pugh classification; (2) the
      Model for End-Stage Liver Disease (MELD) score; (3) the Freeman scale; and (4)
      the Guardiola et al index. The mortality rate on waiting list was 15.9%. All
      studied scores, except Freeman scale, were higher in group D at the time of
      entrance on waiting list (MELD, 17.4 +/- 8 v 12.3 +/- 6, P = .02; Child, 9.9 +/-
      2 v 7.7 +/- 2, P = .002; Freeman, 9.7 +/- 4 v 7.3 +/- 3.9, P = .09; Guardiola,
      2.6 +/- 0.9 v 1.7 +/- 0.7, P = .001). C-statistics of all scores were similar and
      in all cases lower than 0.8 (MELD, 0.75; Child, 0.78; Freeman, 0.65; Guardiola,
      0.79). None of the studied scores have an excellent accuracy to predict prognosis
      of patients on waiting list, mainly in case of populations with high proportion
      of hepatocellular carcinoma. Although the MELD score is rapidly available,
      standardized, and objective, it does not reflect the severity of patients with
      cancer or metabolic disorders.

PMID- 12200781
TI  - In pursuit of the ideal liver allocation model.

PMID- 12200782
TI  - Pulmonary gas exchange abnormalities in liver transplant candidates.
AB  - Abnormal diffusing capacity is the commonest pulmonary dysfunction in liver
      transplant candidates, but severe hypoxemia secondary to hepatopulmonary syndrome
      and significant pulmonary hypertension are pulmonary vascular manifestations of
      cirrhosis that may affect the perioperative course. We prospectively assessed the
      extent of pulmonary dysfunction in patients referred for liver transplantation. A
      total of 57 consecutive patients with chronic liver disease were evaluated. All
      patients had a chest radiograph, standing arterial blood gas on room air,
      pulmonary function testing, and Doppler echocardiogram. Those patients with
      arterial hypoxaemia (PaO(2) < 10 kPa) also underwent (99m)Tc-macroaggregated
      albumin lung scan, and nine patients had agitated normal saline injection during
      echocardiography to define further the existence of pulmonary vascular
      dilatation. Reduced diffusing capacity for carbon monoxide less than 75% of the
      predicted value was found in 29 of 57 (51%) patients. Although elevated alveolar
      arterial oxygen tension difference was detected in 35% (20/57) of the patients,
      only four (7%) patients had hypoxemia. We were unable to find evidence of
      intrapulmonary vascular dilatation either on the lung scan or saline-enhanced
      echocardiography in any of these patients. Reduction in diffusing capacity for
      carbon monoxide was noted in 75% (18/24) of patients who were transplanted for
      primary biliary cirrhosis and was accompanied by widened alveolar-arterial oxygen
      tension in 10 out of 18 (56%) of patients. This study shows that in liver
      transplant candidates, diffusion impairment and widened alveolar-arterial oxygen
      tension difference were frequently detected, especially in patients with primary
      biliary cirrhosis.

PMID- 12200784
TI  - Differential allograft gene expression in acute cellular rejection and recurrence
      of hepatitis C after liver transplantation.
AB  - Treatment of acute cellular rejection (ACR) is associated with increased viral
      load, more severe histologic recurrence, and diminished patient and graft
      survival after liver transplantation for hepatitis C virus (HCV). Recurrence of
      HCV may be difficult to distinguish histologically from ACR. Because the
      immunologic mechanisms of ACR and HCV recurrence are likely to differ, we
      hypothesized that ACR is associated with the expression of a specific subset of
      immune activation genes that may serve as a diagnostic indicator of ACR and
      provide mechanistic insight into the pathophysiology of ACR and recurrence of
      HCV. The goal of the study was to study intragraft gene expression patterns in
      ACR and during recurrence of HCV in HCV-infected recipients. High-density
      microarrays were used to determine relative intragraft gene expression in two
      groups of HCV-infected liver transplant recipients: four with steroid responsive
      ACR by Banff criteria and four age- and gender-matched HCV-infected recipients
      with similar necroinflammatory activity but without histological criteria for
      rejection (no cholangitis or endotheliitis). Immunosuppression was similar in
      both groups. Other etiologies of graft dysfunction were excluded by ultrasound,
      cholangiography, and cultures. High-quality total RNA was extracted from snap
      frozen liver biopsies, reverse transcribed, labeled with biotin, and fragmented
      according to established protocol. Twenty-five genes were relatively
      overexpressed, and 15 were relatively underexpressed by > or = twofold in the ACR
      when compared with the HCV group. ACR was most notably associated with the
      relative overexpression of genes associated with major histocompatibility complex
      I and II, insulin-like growth factor-1 expression, apoptosis induction, and T
      cell activation. In HCV-infected liver transplant recipients, ACR is associated
      with an intragraft gene expression profile that is distinct from that seen during
      recurrence of HCV. These experiments provide evidence that alloimmunity, as
      indicated by expression of T-cell activation and apoptosis-inducing genes, is
      less important in recurrence of HCV than in ACR. Further studies are required to
      determine whether gene expression profiles, either intragraft or in serum, can be
      used for the diagnosis and differentiation of ACR from recurrence of HCV.

PMID- 12200783
TI  - Venous hemodynamics in living donor right lobe liver transplantation.
AB  - We evaluated the influence of portal and hepatic venous hemodynamics on the
      immediate and 3-month postoperative function of living donor right lobe grafts.
      Portal velocity was measured prospectively by ultrasound in 14 consecutive
      donor/recipient pairs. Velocity was converted to flow with the Moriyasu formula.
      Measurements were taken in donors in the operating room and in recipients at 1
      hour after reperfusion and 3 months after transplant. Recipient liver function
      tests were measured postoperatively. Prereperfusion and postreperfusion liver
      biopsies were evaluated and correlated with the hemodynamic and biochemical
      results. There were 11 male (78.6%) and 3 female donors (mean age, 38.9 +/- 9.8
      years) for 10 male (71.4%) and 4 female recipients (mean age, 49.3 +/- 14 years).
      The mean graft/recipient weight ratio was 1.22 +/- 0.3. The mean right portal
      vein pressure was 8 +/- 1.8 mm Hg in donors versus 13 +/- 4.7 mm Hg in recipients
      (P < .05). The mean peak flow velocity (Vmax) in the portal vein in donors was
      47.6 +/- 12.8 cm/sec (normal, 44 cm/sec). One hour after graft reperfusion in the
      recipient, the mean portal Vmax was significantly higher at 94.7 +/- 28.4 cm/sec
      (P = .004), but by 3 months follow-up, mean portal Vmax had fallen to 58.8 +/-
      37.8 (P = .01). Recipient portal vein Vmax highly correlated with portal flow (r
      = 0.7, P = .01). Increased recipient total bilirubin on postoperative day 2
      correlated highly with higher recipient portal flow one hour after transplant (r
      = 0.6; P =.03). Portal vein velocity/flow dramatically increases after
      reperfusion, returning to baseline about 3 months after transplant. Evaluation of
      hepatic and portal venous flow is a relatively easy skill to acquire.
      Intraoperative ultrasound may enable the surgeon to predict graft dysfunction and
      possibly, may be used to implement pre-emptive therapies.

PMID- 12200785
TI  - Engraftment assessment in human and mouse liver tissue after sex-mismatched liver
      cell transplantation by real-time quantitative PCR for Y chromosome sequences.
AB  - Transplanted hepatocytes can engraft, proliferate, and function permanently in
      host animals. After one cell infusion, however, engrafted hepatocytes constitute
      only between 1 in 200 to 1 in 3,000 host liver cells. Although transplanted cells
      can be identified using biochemical and molecular techniques, more accurate
      methods are needed to evaluate interventions that could improve cell engraftment
      rates. Real-time polymerase chain reaction (PCR) was done using primers and
      probes complementary to human testis determining gene (SRY) and mouse testis
      specific Y-encoded protein (TSPY) pseudogene. Tissue samples from human or mouse
      recipients of liver cell transplantation were used to determine the test ability
      to detect transplanted cell DNA. Real-time PCR for the human SRY and mouse TSPY
      were species- and sex-specific. These two tests were sensitive in the detection
      of male DNA. Test sensitivity was consistently found at minimum 1:10,000 of male
      and female DNA mixing curve in both human SRY and mouse TSPY assays. The optimal
      amount of sample DNA per reaction to produce the highest sensitivity was 300 ng
      to 1 microg. Real-time PCR gave similar results whether standard male-female
      mixtures were prepared from liver cells or mononuclear cells. Engraftment of male
      liver cells in female liver tissues in mice and humans ranging from 0.125% to
      0.257% was successfully measured using this method. Real-time PCR for SRY and
      TSPY affords a specific, sensitive, and reproducible tool for chimerism analysis
      in transplanted human and mouse liver tissues. This method could be used to
      optimize current models of cell transplantation.

PMID- 12200786
TI  - Donor evaluation, donor risks, donor outcome, and donor quality of life in adult
      to-adult living donor liver transplantation.
AB  - Right lobe living donor liver transplantation (LD-LTx) is currently performed at
      an increasing number of transplant centers. Donor selection, donor safety, donor
      recovery, and postdonation psychological impairment are essential criteria to
      determine whether and under which conditions LD-LTx is justifiable. Before
      commencing the LD-LTx program, approval was obtained from the local ethics
      committee. Potential donors underwent a comprehensive multistep evaluation
      protocol to exclude any conditions that could lead to an increased operative
      risk. Each donation was approved by the local Living Donation Commission. Follow
      up investigations were performed after 6 and 12 months. Liver regeneration was
      assessed by computed tomography scan and magnetic resonance imaging scan derived
      volumetries. Quality of life (QOL) was investigated according to the Anamnestic
      Comparative Self-Assessment Scale (ACSA) before donation, and 6 and 12 months
      after donation. As of December 2001, 43 right lobe living donations have been
      performed at the Charite, Campus Virchow, Berlin. None of the donors died or has
      suffered life-threatening or persisting complications. All patients recovered
      completely. Complications occured in 8 donors (18%). The incidence of
      perioperative surgical complications was 9%, comprising temporary biliary
      leakages (n = 3; 6.8%) as well as postoperative bleeding (n = 1). Liver volume
      regeneration approximated 72% +/- 15% of predonation volume by 6 months and 85%
      +/- 18% (mean +/- SD) by 12 months. There was no evidence of significant
      psychological impairment after donation. QOL increased after donation compared
      with the preoperative state (P < .05). In our experience, LD-LTx has proven to be
      a practicable and safe procedure. However, there is a considerable risk of
      postoperative complications. The donor selection process plays a pivotal role in
      preventing complications. The discussion of potential risks, especially potential
      life-threatening risks, must be an integral part of informed consent.

PMID- 12200787
TI  - Nelfinavir, a protease inhibitor, increases sirolimus levels in a liver
      transplantation patient: a case report.
AB  - With the increasing success of liver transplantation and the proven effectiveness
      of highly active retroviral therapy in HIV-positive patients, liver
      transplantation has been performed successfully in selected HIV-positive
      recipients with CD4 and an HIV viral load response to highly active
      antiretroviral therapy. In these patients, an interaction between a protease
      inhibitor (nelfinavir) and tacrolimus has been shown. The effect of nelfinavir on
      the pharmacokinetics of sirolimus, a newer immunosuppressive drug, is currently
      not known. The goal of the present case report is to document the interaction
      between sirolimus and nelfinavir in a liver transplantation patient. A 40-year
      old woman who was HIV positive underwent a cadaveric liver transplantation for
      acute fulminant liver failure secondary to nevirapine (a nonnucleoside reverse
      transcriptase inhibitor). Postoperatively, she was treated with tacrolimus and
      steroids. She experienced steroid-resistant rejection and was started on
      sirolimus on the 17th postoperative day. Kinetic parameters were determined after
      a 2-mg oral dose of sirolimus and 250 mg of nelfinavir by collecting multiple
      peripheral venous blood samples before and after sirolimus administration. The
      kinetic parameters were compared with parameters from three liver transplantation
      patients on sirolimus who were not on nelfinavir. After normalizing the kinetic
      parameters to sirolimus dose of 1 mg/d, 0-hour and 24-hour trough sirolimus
      concentrations were nine-fold and five-fold higher for the patient who was on
      nelfinavir, compared with those who were not on nelfinavir. The maximum
      concentration was 3.2 times higher, the area under the concentration curve was
      1.6 times higher, and the terminal disposition half-life was prolonged by 60%.
      The time to reach the peak concentration was 1 hour in all patients. Increase in
      trough concentration, peak concentration area under the curve concentration, and
      prolongation of half-life of sirolimus has been shown in a patient who was on a
      low dose (one fifth the recommended dose) of nelfinavir.

PMID- 12200788
TI  - The interaction between antiretroviral agents and tacrolimus in liver and kidney
      transplant patients.
AB  - Solid organ transplantations have been performed successfully in selected HIV
      positive patients with highly active antiretrovirus therapy (HAART). However,
      some of the medications in the HAART regimen require metabolism via the
      cytochrome P4503A, the same enzyme complex responsible for clearance of the
      calcineurin inhibitors cyclosporine and tacrolimus. Several case reports have
      described significant interactions between the agents used in HAART and
      immunosuppressive drugs. The goal of this report is to examine the extent of
      potential drug interactions between antiretroviral agents and tacrolimus after
      liver and kidney transplantation. Seven liver transplant (LTx) patients (M = 6, F
      = 1) and four kidney transplant (KTx) patients (M = 4) infected with HIV
      underwent surgery between September 1997 and January 2001. Initial
      immunosuppression consisted of tacrolimus and steroids for LTx patients or
      tacrolimus, steroids, and mycophenolate mofetil for KTx recipients. Their current
      baseline immunosuppression and HAART regimen were examined retrospectively. Of
      the seven liver recipients, one (case 4) died 2 weeks after LTx and never
      received HAART therapy posttransplantation. The remaining six patients were
      placed on a regimen consisting of two nucleoside reverse transcriptase inhibitors
      (NRTI) and one protease inhibitor (PI) (nelfinavir in 5, indinavir in 1) based on
      known viral sensitivities or history of a previous clinical response. Kidney
      recipients received NRTI and nonnucleoside reverse transcriptase inhibitors
      (NNRTI). The mean dose of tacrolimus in liver recipients was 0.6 mg/d, with mean
      trough concentration of 9.7 mg/mL. Compared with historic controls (liver
      transplant patients not on HAART), the average tacrolimus dose was 16-fold lower
      in patients on HAART. In contrast to liver recipients, HIV-positive kidney
      recipients not on PI therapy required a mean tacrolimus dose of 9.5 mg/d to
      maintain a mean trough concentration of 9.6 ng/mL. Of the two protease inhibitors
      used, nelfinavir seems to have a more profound effect than indinavir. When
      patients on nelfinavir alone (n = 5) were compared with a control group not on
      antiretroviral therapy, the need for a tacrolimus dose was 38 times lower (mean
      dose, 0.26 mg/d). Profound drug interactions between PI and tacrolimus have been
      observed requiring up to 50-fold reductions in dosage. This effect seems to be
      most pronounced with the use of nelfinavir as opposed to indinavir, although
      further experience is required to confirm this observation. In contrast, HAART
      using NRTI and NNRTI without the use of PI, as shown in kidney recipients,
      produces less significant effects on tacrolimus metabolism. Great caution and
      frequent drug level monitoring are necessary when HAART is introduced or
      withdrawn in HIV-positive recipients of organ transplants.

PMID- 12200789
TI  - Cryptococcus neoformans infection.

PMID- 12200790
TI  - Predicting behavior of immunosuppressants in liver transplantation.

PMID- 12200791
TI  - The new liver allocation system: moving toward evidence-based transplantation
      policy.
AB  - In 1999, the Institute of Medicine suggested that instituting a continuous
      disease severity score that de-emphasizes waiting time could improve the
      allocation of cadaveric livers for transplantation. This report describes the
      development and initial implementation of this new plan. The goal was to develop
      a continuous disease severity scale that uses objective, readily available
      variables to predict mortality risk in patients with end-stage liver disease and
      reduce the emphasis on waiting time. Mechanisms were also developed for inclusion
      of good transplant candidates who do not have high risk of death but for whom
      transplantation may be urgent. The Model for End-Stage Liver Disease (MELD) and
      Pediatric End-Stage Liver Disease (PELD) scores were selected as the basis for
      the new allocation policy because of their high degree of accuracy for predicting
      death in patients having a variety of liver disease etiologies and across a broad
      spectrum of liver disease severity. Except for the most urgent patients, all
      patients will be ranked continuously under the new policy by their MELD/PELD
      score. Waiting time is used only to prioritize patients with identical MELD/PELD
      scores. Patients who are not well served by the MELD/PELD scores can be
      prioritized through a regionalized peer review system. This new liver allocation
      plan is based on more objective, verifiable measures of disease severity with
      minimal emphasis on waiting time. Application of such risk models provides an
      evidenced-based approach on which to base further refinements and improve the
      model.

PMID- 12200792
TI  - Living donor in urgent cases: ethical hazard?

PMID- 12200793
TI  - Meta-analysis of subcutaneous versus intravenous epoetin in maintenance treatment
      of anemia in hemodialysis patients.
AB  - BACKGROUND: Clinical and pharmacokinetic studies have shown that target
      hemoglobin or hematocrit levels can be maintained using a reduced recombinant
      human erythropoietin (epoetin) dosage by switching from intravenous (IV) to
      subcutaneous (SC) administration. METHODS: We conducted a meta-analysis of
      comparative studies of epoetin administered IV versus SC to assess the relative
      costs of these administration routes. Twenty-seven prospective clinical studies
      involving 916 patients were included in the analysis. The average difference
      between IV and SC doses of epoetin and average difference in drug costs between
      administration routes were determined. RESULTS: The average reduction in dose in
      patients treated with SC versus IV epoetin was 48 IU/kg/wk (P < 0.001),
      representing an average annual cost savings with SC administration of US $1,761
      +/- $1,080 (SD) per patient. The difference between SC and IV doses was similar
      in both parallel- and crossover-design studies. A retrospective US survey showed
      a dose reduction of 26 IU/kg/wk (P < 0.001) with SC administration, translating
      to an annual savings of $946 per patient. CONCLUSION: This study indicates that
      the cost of epoetin is reduced substantially when administered SC in comparison
      to IV. Recommendations of current US and European guidelines, which encourage the
      use of SC administration, not only have a sound rationale in terms of efficacy
      and safety, but also have a sound economic basis.

PMID- 12200794
TI  - Mycophenolate mofetil in lupus glomerulonephritis.
AB  - The optimal treatment of severe lupus nephritis is unclear. Regimens consisting
      of steroid and cyclophosphamide (CYC) appear to be most effective. However, up to
      15% of patients are refractory to CYC treatment, and 30% to 50% of patients still
      develop end-stage renal disease. Moreover, infection and gonadal toxicity are
      major concerns of CYC use in patients of the reproductive age. More effective,
      but less toxic, regimens are needed. Mycophenolate mofetil (MMF) is a new
      immunosuppressive agent that selectively inhibits activated lymphocytes and renal
      mesangial cells. Experience with MMF in solid-organ transplantation has shown the
      safety of this drug and its superiority over azathioprine (AZA) in the prevention
      of acute graft rejection. Data from experimental models of immune-mediated
      glomerulonephritis, particularly lupus nephritis, have shown that MMF ameliorates
      autoimmune phenomena, retards renal damage, and improves outcome. Although the
      use of MMF in lupus nephritis is still in its preliminary stage, uncontrolled
      experience has confirmed its efficacy in patients with serious disease
      recalcitrant to conventional cytotoxic agents. Controlled studies, albeit small
      and lacking statistical power, have shown that MMF is as effective as CYC in the
      induction of renal remission in the short term. With the current dosage used in
      systemic lupus erythematosus, MMF appears to be well tolerated, with no serious
      toxicities reported. Significantly less ovarian toxicity compared with CYC is
      particularly attractive for the consideration of MMF in lupus nephritis. However,
      the lack of long-term efficacy data and comparative studies with standard CYC
      regimens is the major deterrent for the first-line use of MMF in high-risk
      patients at this juncture.

PMID- 12200795
TI  - Antiproteinuric versus antihypertensive effects of high-dose ACE inhibitor
      therapy.
AB  - BACKGROUND: Angiotensin-converting enzyme (ACE) inhibitors effectively reduce
      proteinuria; however, the optimal antiproteinuric dose is still unknown. We
      conducted this study to determine whether an increase in ACE-inhibitor dose above
      the maximal antihypertensive effect has additional antiproteinuric potential.
      METHODS: Twenty-three proteinuric patients were administered the ACE inhibitor
      spirapril at a starting dose of 3 to 6 mg/d. The dose was increased every 6 weeks
      until the maximal antihypertensive effect, assessed by 24-hour ambulatory blood
      pressure (ABP) monitoring, was achieved (spir(max)), then increased to a
      supramaximal dose (spir(supramax)). Renal parameters, urinary protein excretion,
      and systemic activity of the renin-angiotensin system were compared between
      baseline, spir(max), and spir(supramax). Glomerular filtration rate and renal
      plasma flow were determined before the administration of spirapril and after
      administration of the supramaximal dose. RESULTS: Median ABP and proteinuria
      decreased significantly between baseline and spir(max) (median, 102 mm Hg; range,
      82 to 122 mm Hg versus 97 mm Hg; range, 82 to 113 mm Hg; median protein, 2.56
      g/d; range, 1.05 to 22.1 g/d versus 1.73 g/d; range, 0.42 to 4.7 g/d). Both
      creatinine level and creatinine clearance remained unchanged. Suppression of
      angiotensin II formation led to a significant increase in renin and angiotensin I
      concentrations and a nonsignificant decrease in aldosterone levels. The increase
      in spirapril to a supramaximal dose had no further effect on serum renin or
      angiotensin I levels or proteinuria. There was an additional slight decrease in
      aldosterone levels and, subsequently, a significantly lower level than at
      baseline. CONCLUSION: Our results show that the antiproteinuric effect of
      spirapril is associated with its antihypertensive effect. Although high-dose ACE
      inhibitor therapy has no additional influence on proteinuria, a possible
      beneficial long-term effect cannot be ruled out.

PMID- 12200796
TI  - Plasma 3-deoxyglucosone elevation in chronic renal failure is associated with
      increased aldose reductase in erythrocytes.
AB  - BACKGROUND: Serum concentrations of 3-deoxyglucosone (3DG), a highly reactive
      dicarbonyl compound, are elevated in uremic patients. Aldose reductase (AR) is an
      enzyme involved in both the detoxification of 3DG and producing precursors of
      3DG. METHODS: We examined the relationship between plasma 3DG and erythrocyte AR
      content in uremic patients. Patients were divided into three groups: (1)
      progressive renal disease without hemodialysis (HD; chronic renal failure [CRF]
      group), (2) patients without diabetes mellitus (DM) treated with maintenance HD
      (HD group), and (3) patients with DM treated with maintenance HD (DM-HD group).
      High-performance liquid chromatography was used to measure 3DG, and erythrocyte
      AR was measured by means of enzyme-linked immunosorbent assay. RESULTS: Both 3DG
      and erythrocyte AR levels were significantly greater in the CRF, HD, and DM-HD
      groups than in healthy controls. These results did not change after HD sessions
      in the HD or DM-HD groups. Serum creatinine levels correlated with 3DG and
      erythrocyte AR levels in the control and CRF groups (3DG: r = 0.67; P < 0.001;
      erythrocyte AR: r = 0.71; P < 0.001). Both erythrocyte AR and 3DG levels then
      increased as renal function declined. A positive correlation was seen between 3DG
      and erythrocyte AR levels in all groups (r = 0.65; P < 0.001), and also between
      plasma osmolality and erythrocyte AR level (r = 0.46; P < 0.001). CONCLUSION:
      Both erythrocyte AR and 3DG levels are increased in uremic patients, and these
      increases could possibly contribute to the development of uremic symptoms.

PMID- 12200797
TI  - The prevalence of peripheral arterial disease and medial arterial calcification
      in patients with chronic renal failure: requirements for diagnostics.
AB  - BACKGROUND: Knowledge of the prevalence of peripheral arterial disease (PAD) in
      patients with chronic renal failure (CRF) is limited because of a lack of
      uniformity in disease definition and recognition. Furthermore, little is known of
      the prevalence of medial arterial calcification (MAC) in patients with CRF. Our
      goal is to study the prevalence of PAD and MAC defined by ankle brachial index
      (ABI) or toe brachial index (TBI) measurements in a Finnish population of
      patients with CRF consisting of predialysis and dialysis patients, as well as
      renal transplant recipients. METHODS: We examined 136 patients with CRF and 59
      control subjects. Fifty-nine of the patients with CRF had moderate to severe
      predialysis CRF, 36 patients were on dialysis treatment, and 41 were renal
      transplant recipients. Mean age of patients was 51.9 +/- 11.5 years, and 39
      patients (29%) had diabetes. ABI and TBI were measured by means of
      photoplethysmography. The definition of PAD required an ABI value of 0.90 or
      less, a TBI value of 0.60 or less, or a previous positive lower-extremity
      angiogram result. ABI values of 1.3 or greater or incompressible arteries at
      ankle level indicated MAC. The presence of claudication was determined by an
      interview. RESULTS: Prevalences of PAD on this study were 22.0% in patients with
      predialysis CRF, 30.6% in patients on dialysis treatment, 14.6% in renal
      transplant recipients, and 1.7% in the control group (P = 0.001). Prevalences of
      MAC were 23.7%, 41.7%, 23.1%, and 3.4% (P < 0.001), respectively. Only 9 patients
      had claudication, and 6 of those patients had PAD. CONCLUSION: Both asymptomatic
      PAD and MAC are common in patients with CRF. Therefore, we recommend the use of
      both ABI and TBI measurements in the evaluation of PAD in patients with CRF.

PMID- 12200798
TI  - Plasma sulfur amino acids in relation to cardiovascular disease, nutritional
      status, and diabetes mellitus in patients with chronic renal failure at start of
      dialysis therapy.
AB  - Sulfur amino acids (sAAs) are potential candidates as risk factors for
      cardiovascular disease (CVD). However, we recently reported that chronic
      hemodialysis patients with CVD had a greater prevalence of malnutrition,
      hypoalbuminemia, and lower plasma total homocysteine (tHcy) levels than those
      without CVD. In this cross-sectional study, we examined the relationship of
      plasma sAAs to CVD and nutritional status in 151 patients with chronic renal
      failure (CRF) close to the start of regular dialysis treatment (33 +/- 7 days
      before the first dialysis treatment). Clinical signs of CVD were present in 32%
      of patients with CRF, 41% had malnutrition assessed by subjective global
      nutritional assessment (SGNA) score, and 26% had diabetes mellitus (DM). Plasma
      tHcy levels were high in 91% of patients, as were plasma total cysteine (tCys)
      levels, whereas plasma methionine (Met) and taurine (Tau) levels were normal.
      Patients with CRF who had CVD were older, more often malnourished, and had lower
      tHcy and serum albumin (s-albumin) levels and a greater frequency of DM than
      those without CVD. Plasma tCys, Met, and Tau levels did not differ between
      patients with CRF with and without CVD. The tCys-tHcy ratio was higher in
      patients with CVD and related to SGNA score and DM. Moreover, this ratio, but not
      tHcy or tCys level, correlated with age and triglyceride, total cholesterol, and
      apolipoprotein B levels. Malnutrition and hypoalbuminemia were associated with
      low plasma sAA levels (tHcy, Met, and Tau); tCys was related to s-albumin level,
      but not SGNA score. Among patients with diabetes, sAA levels did not differ
      between patients with and without CVD or between malnourished and well-nourished
      patients. In conclusion, patients with CRF at the start of dialysis treatment
      with CVD were more often diabetic, malnourished, and had lower s-albumin and tHcy
      levels and a higher tCys-tHcy ratio than patients with no CVD. tCys-tHcy ratio,
      but not tHcy or tCys levels per se, was related to cardiovascular risk factors,
      suggesting that cysteine may have a role in the development of CVD. Malnutrition,
      hypoalbuminemia, and DM in patients with CRF influence sAA levels, mainly plasma
      tHcy, which should be considered when evaluating hyperhomocysteinemia as a
      cardiovascular risk factor.

PMID- 12200799
TI  - Nephropathy in siblings of African Americans with overt type 2 diabetic
      nephropathy.
AB  - BACKGROUND: The prevalence of abnormal proteinuria and elevated serum creatinine
      (sCr) concentrations in diabetic sibs of African Americans (AAs) with overt type
      2 diabetic nephropathy (DN) or end-stage renal disease (ESRD) is unknown.
      METHODS: We measured urine albumin-creatinine (UAC) ratio, sCr, and hemoglobin
      A1c (HbA1c) in 211 sibs from 66 families (66 unrelated index cases with overt
      type 2 DN/ESRD, 132 of their diabetic sibs, and 13 of their nondiabetic sibs).
      Overt DN was defined as a UAC ratio of 1,000 mg/g or greater or ESRD attributed
      to diabetes. All index cases had at least one diabetic sib screened. RESULTS:
      Given similar mean ages and body mass indices, nondiabetic sibs had lower UAC
      ratios and HbA1c values compared with diabetic sibs and index cases (Wilcoxon's
      rank-sum test, all P < 0.006). More than 60% of index cases had at least one
      diabetic sib with a UAC ratio of 30 or greater and 300 mg/g or less. Nearly 35%
      of index cases had at least one sib with a UAC ratio greater than 300 mg/g.
      Nearly 24% of index cases had at least one sib with an elevated sCr level (> or
      =1.4 mg/dL [124 micromol/L] in women, > or =1.6 mg/dL [141 micromol/L] in men).
      CONCLUSION: Asymptomatic elevations in urinary albumin excretion and sCr levels
      are frequently present in diabetic sibs of AA individuals with overt type 2 DN.
      Diabetic sibs of AA individuals with type 2 DN should be the focus of intensive
      screening and intervention programs to slow the current epidemic of diabetic
      ESRD.

PMID- 12200800
TI  - In human IgA nephropathy uteroglobin does not play the role inferred from
      transgenic mice.
AB  - BACKGROUND: Uteroglobin (UG)-knockout and UG-antisense transgenic mice develop
      clinical and pathological features of immunoglobulin A (IgA) nephropathy with
      heavy proteinuria. These models suggested that UG, an anti-inflammatory protein
      with high affinity for fibronectin (Fn), prevents the formation of IgA-Fn
      complexes and mesangial deposits in mice. We aim to elucidate whether similar
      mechanisms underlie the development and severity of human IgA nephropathy.
      METHODS: Specific enzyme-linked immunosorbent assays were devised to detect serum
      levels of UG binding to Fn or incorporated into IgA-Fn complexes and IgA binding
      to Fn or collagen IV. Sera from 75 patients with IgA nephropathy with normal
      renal function and various degrees of proteinuria (0.2 to 5 g/d of protein)
      stable over the previous 3 months without therapy were investigated and compared
      with healthy controls. RESULTS: Levels of UG binding to Fn were similar in
      patients with IgA nephropathy and healthy controls. UG incorporated into
      circulating IgA-Fn complexes, as well as levels of IgA-Fn complexes and IgA
      binding Fn and collagen IV, were significantly greater in patients than healthy
      controls. Greater amounts of UG incorporated into IgA-Fn complexes reduced the
      risk for proteinuria with protein greater than 1 g/d (odds ratio = 0.67; P <
      0.001). Logistic regression analysis assigned a predictive value for proteinuria
      persistently greater than 1 g/d of protein to lower amounts of UG incorporated
      into IgA-Fn complexes (R = -0.267; P = 0.008) and increased binding of IgA to
      collagen IV (R = 0.214; P = 0.0003). CONCLUSION: This first report of human IgA
      nephropathy after the publication of the mouse model shows that UG is not reduced
      in circulation and is even increased in IgA-Fn complexes. Because aberrant IgA1
      glycosylation is the event initiating IgA nephropathy in humans, we speculate
      that the enhanced incorporation of UG into IgA-Fn complexes might represent
      feedback to reduce the formation of macromolecular aggregates.

PMID- 12200801
TI  - Ovarian manifestations in women with autosomal dominant polycystic kidney
      disease.
AB  - BACKGROUND: Ovarian cysts are found in some premenopausal women with autosomal
      dominant polycystic kidney disease (ADPKD). Liver cysts are the major extrarenal
      manifestations, frequently found in postmenopausal women. Female steroid hormones
      may regulate hepatic cystogenesis, but ovarian manifestations in postmenopausal
      women are unknown. The aim of the present study is to investigate possible
      ovarian manifestations associated with ADPKD in premenopausal and postmenopausal
      women. METHODS: The study group included 19 premenopausal or postmenopausal women
      with ADPKD and 19 age- and parity-matched control women with no history of renal
      disease. Ovarian structures and volumes were measured by means of transvaginal
      ultrasonography. RESULTS: Three of 8 premenopausal and 1 of 11 postmenopausal
      women with ADPKD had a small unilateral single ovarian cyst; there were none in
      controls. Eight women with ADPKD and 8 controls of premenopausal age had similar
      ovarian volumes (4.92 +/- 2.97 versus 3.92 +/- 2.60 cm3). Eleven postmenopausal
      women with ADPKD had an increased mean ovarian volume compared with 11
      postmenopausal controls (4.11 +/- 2.60 versus 1.66 +/- 0.96 cm3; P < 0.01).
      Ovarian volume was not associated with the use of hormonal replacement therapy or
      impaired renal function in postmenopausal women with ADPKD. CONCLUSION: ADPKD is
      not associated with cystic ovaries, although single ovarian cysts are
      occasionally found. Equal ovarian volumes between premenopausal and
      postmenopausal women with ADPKD suggest a possible indirect effect of polycystic
      kidneys on gonads in aging women.

PMID- 12200802
TI  - Long-term sodium balance in humans in a terrestrial space station simulation
      study.
AB  - BACKGROUND: Sodium accumulation has been considered to take place in the
      extracellular space, leading to water retention and weight gain. This traditional
      view has been questioned by recent studies that showed sodium accumulation in
      humans without expansion of the extracellular volume. We investigated sodium
      balance and its impact on body weight (BW) during a long-term balance study.
      METHODS: Three healthy subjects were confined to a terrestrial MIR simulator for
      135 days under conditions simulating a long-term spaceflight. During the entire
      isolation period, we meticulously measured daily sodium balance and its
      contribution to BW. RESULTS: During the study period, subjects accumulated
      between 2,973 and 7,324 mmol of sodium and gained between 5.1 and 9.3 kg in
      weight. In all subjects, there was a positive correlation between changes in
      total-body sodium (DeltaTBS) content and BW, reflecting sodium-associated volume
      expansion. However, toward the end of isolation, sodium gain exceeded weight
      gain, suggesting that sodium accumulated in an osmotically inactive form.
      Especially at the onset of the experiment, two subjects showed inverse
      correlations between DeltaTBS and BW. CONCLUSION: The finding of sodium gain
      without weight gain is in contradiction to the widely accepted theory that
      changes in TBS levels are accompanied by changes in extracellular volume. We
      suggest the existence of a sodium reservoir with the ability to store significant
      amounts of sodium in an osmotically inactive form. This reservoir might be
      located in bone, dense connective tissue, or cartilage.

PMID- 12200803
TI  - Predictors of alkalosis after liver transplantation.
AB  - BACKGROUND: Metabolic alkalosis (MA) is common after orthotopic liver
      transplantation (OLT). METHODS: The study was conducted to identify factors
      associated with MA after 285 OLTs. MA, defined as total carbon dioxide content of
      30 mEq/L or greater, developed in 115 patients (40%) within the first 3
      postoperative days. RESULTS: By univariate analysis, patients with MA had a
      greater preoperative carbon dioxide content (24.4 +/- 3 versus 22.9 +/- 2.9
      mEq/L; P < 0.0001) and hematocrit (35% +/- 5% versus 33% +/- 6%; P < 0.02), but
      lower creatinine (0.9 +/- 0.5 versus 1.2 +/- 1.2 mg/dL; P < 0.001) and blood urea
      nitrogen levels (15 +/- 12 versus 19 +/- 17 mg/dL; P < 0.001) compared with
      controls. Patients with MA were administered more citrate intraoperatively
      compared with controls (6.2 +/- 5.2 versus 4.5 +/- 3.6 mEq/kg of body weight; P <
      0.02). Patients with MA had a lower postoperative potassium level (3.7 +/- 0.4
      versus 4 +/- 0.5 mEq/L; P < 0.0001) and cumulative fluid balance (-0.66 +/- 1.87
      versus +0.003 +/- 3.9 L; P < 0.007) compared with controls. By multivariate
      analysis, preoperative carbon dioxide content (odds ratio, 1.19; 95% confidence
      interval [CI], 1.08 to 1.31 per mEq/L), creatinine level (odds ratio, 0.61; 95%
      CI, 0.39 to 0.96 per mg/dL), intraoperative administered citrate (odds ratio,
      3.35; 95% CI, 1.71 to 6.53 per 10 mEq/kg body weight), and postoperative
      potassium level (odds ratio, 0.32; 95% CI, 0.18 to 0.57 per mEq/L) were
      independently associated with MA. MA was not associated with increased hospital
      mortality (7.8% versus 8.2%, MA versus controls). However, patients with MA spent
      more time on mechanical ventilation than controls (5 +/- 0.8 versus 3 +/- 0.6
      days; P < or = 0.03). CONCLUSION: Preoperative total carbon dioxide content,
      renal function, intraoperative administered citrate, and postoperative potassium
      level are independently associated with MA after primary OLT.

PMID- 12200804
TI  - A single-center review of the death notification form: discontinuing dialysis
      before death is not a surrogate for withdrawal from dialysis.
AB  - BACKGROUND: Form 2746, the death notification form, is the primary source of data
      on cause of death for patients with end-stage renal disease in the United States.
      Since the revised form was introduced in May 1990, withdrawal from dialysis is no
      longer a specific cause of death code. A separate section of form 2746 asks
      whether dialysis was discontinued before death. Based on US Renal Data System
      data from form 2746, more than 20% of dialysis patients discontinue dialysis
      before death. It is not known whether stopping dialysis is a proximate cause of
      death in these patients. METHODS: Two hundred twelve death notification forms
      completed between January 1, 1993, and December 31, 2000, from a single dialysis
      center were reviewed for location of death, primary and secondary causes of
      death, and whether dialysis therapy was discontinued before death. Dialysis unit
      and hospital billing records of patients who discontinued dialysis before death
      were reviewed to obtain the dates of hospitalization and last dialysis treatment
      before death. RESULTS: Fifty-six patients (26%) discontinued dialysis therapy
      before death. In only 8 of those patients' deaths (8 of 212 deaths; 4% of all
      patient deaths), nephrologists used form 2746 to attribute the death to uremia
      from stopping dialysis therapy. Time in days from the last dialysis treatment to
      death in these 8 patients was longer than in the remaining 48 patients who
      stopped dialysis therapy before death, but in whom cause of death was not coded
      as uremia (median, 12.5 versus 5 days, respectively; P = 0.01). Patients who
      stopped dialysis therapy before death were more likely to have malignancy and
      less likely to have cardiovascular disease coded as cause of death. Most patients
      died in the hospital; only 2 patients died in hospice. CONCLUSION: There is
      physician variability in interpretation of discontinuation of dialysis before
      death. Thirty percent of patients who discontinued dialysis therapy before death
      died 3 or fewer days from their last dialysis treatment, making uremia an
      unlikely cause of death, but suggesting that nephrologists wanted to note that a
      decision not to continue dialysis therapy had been made before the patient died.
      Discontinuing dialysis therapy as noted on the death notification form is not a
      surrogate for withdrawal from dialysis as a cause of death. Providing criteria
      for reporting discontinuing dialysis therapy would allow us to clarify the
      incidence of withdrawal from dialysis as a cause of death.

PMID- 12200805
TI  - Intravenous and subcutaneous weight-based dosing of the low molecular weight
      heparin tinzaparin (Innohep) in end-stage renal disease patients undergoing
      chronic hemodialysis.
AB  - BACKGROUND: Patients with end-stage renal disease are subject to a broad range of
      thrombotic complications. Low molecular weight heparins (LMWHs) are effective
      antithrombotic agents; however, they are cleared largely by renal mechanisms,
      raising uncertainty about their use in renally impaired patients. METHODS: Twelve
      chronic hemodialysis subjects were administered two single doses of the LMWH
      tinzaparin, 75 IU/kg, 2 weeks apart: subcutaneously (SC) on an off-dialysis day
      and intravenously (IV) just before dialysis. RESULTS: Mean maximal anti-factor Xa
      (anti-Xa) activity was 0.33 IU/mL 4.0 hours after SC administration and 1.33
      IU/mL 0.25 hours after IV administration. Anti-Xa half-lives were 3.89 and 2.31
      hours, respectively. Anti-Xa activity returned to baseline within 24 hours of
      administration by either route. Consistent with population pharmacokinetic
      analyses of clinical study subjects with severe renal impairment, anti-Xa
      clearance after tinzaparin administration was reduced 28% relative to subjects
      with normal renal function. All 12 study subjects completed hemodialysis without
      requiring additional anticoagulation. One subject had minimal clotting in the
      dialyzer drip chamber, and one subject had mild prolonged bleeding at the
      vascular access site after dialysis needle removal. No major bleeding events
      occurred. CONCLUSION: Tinzaparin, 75 IU/kg, SC on an off-dialysis day and IV just
      before dialysis is well tolerated in chronic hemodialysis patients. The weight
      based regimen of 75 IU/kg IV just before dialysis provides adequate
      anticoagulation. SC weight-based dosing on off-dialysis days is a feasible
      regimen for further clinical thromboprophylaxis efficacy studies in hemodialysis
      patients. The risk for clinical overdose in severely renally impaired patients
      using this weight-based regimen of tinzaparin is unlikely.

PMID- 12200806
TI  - Health care resource utilization and the impact of anemia management in patients
      with chronic kidney disease.
AB  - BACKGROUND: Limited information exists on resource utilization patterns and
      overall patient management of chronic kidney disease (CKD) before the initiation
      of dialysis therapy. METHODS: A retrospective claims analysis from January 1997
      to December 1999 was conducted using a managed care database on 1,936 incident
      dialysis patients, examining the 12 months preceding dialysis initiation to
      evaluate whether managed care patients with CKD are receiving expected
      interventions and appropriate management of CKD. RESULTS: Mean age was 66.8
      years, 46% were women, 91.2% had claims for facility services, 97.6% had claims
      for professional services, and 95.7% had claims for outpatient pharmacy, with
      mean costs per patient of $26,204, $9,623, and $1,503, respectively. Sixty-two
      percent of patients were hospitalized, averaging 1.3 admissions annually
      ($14,818/admission; average, 7.8 d/admission). Despite high overall resource use,
      treatments for preparation for dialysis therapy, appropriate tests, and
      nutritional supplements (eg, phosphate binders, B-complex combinations, and
      vitamins with iron) were administered infrequently. Comorbid conditions, such as
      anemia (47.4%) and diabetes (53%), were appropriately addressed with
      erythropoietin (10.5%) and angiotensin-converting enzyme inhibitors (38%) in only
      a minority of cases. In preparation for dialysis therapy, only 20.8% underwent a
      vascular access procedure. CONCLUSION: Although patients consumed significant
      amounts of resources during the 12 months before dialysis initiation, many were
      not using expected resources for the appropriate management of CKD. A number of
      opportunities exist to improve predialysis care through better management of
      these conditions.

PMID- 12200807
TI  - Influence of the cyclic variation of hydration status on hemoglobin levels in
      hemodialysis patients.
AB  - BACKGROUND: Maintenance hemodialysis (HD) patients were studied to assess the
      effect on hemoglobin (Hb) concentration induced by the cyclic variation in
      hydration status. METHODS: Forty-nine HD patients were examined in three
      consecutive HD sessions in a 1-week treatment period. In a subgroup of 23
      patients, Hb levels also were investigated during the long interdialytic
      interval. RESULTS: Hb levels at the end of the long interdialytic interval were
      significantly lower by 0.5 to 0.6 g/dL (5 to 6 g/L) than those at the end of
      short intervals. Among all pre-HD and post-HD Hb values, levels measured at the
      end of short intervals were closest to the mean Hb value of the week, derived
      from calculation of the area under the curve (12.0 +/- 0.2 g/dL [120 +/- 2 g/L]).
      Intradialytic Hb increments were different in the three sessions (+1.6 +/- 0.1
      g/dL [+16 +/- 1 g/L] after the long interval, +1.1 +/- 0.1 g/dL [+11 +/- 1 g/L]
      and +1.1 +/- 0.1 g/dL [+11 +/- 1 g/L] after short intervals [P < 0.001] and
      proportionate to weight loss [-3.4 +/- 0.1, -2.7 +/- 0.1, and -2.6 +/- 0.1 kg,
      respectively; P < 0.001]). Hb level increment and weight loss correlated directly
      (r = 0.527; P < 0.0001); each 1 L of ultrafiltration (UF) led to an increase in
      Hb level of approximately 0.4 g/dL (4 g/L). Plasma refilling accounted for an
      approximately 45% decrement in the intradialytic increase in Hb level 2 hours
      post-HD. CONCLUSION: This study suggests that: (1) the end of the short
      interdialytic period is the most appropriate timing for anemia assessment, and
      (2) the remarkable hemodiluting effect of post-HD plasma refilling protects
      against excessive increments in Hb levels induced by UF.

PMID- 12200808
TI  - Linear decay of relative blood volume during ultrafiltration predicts hemodynamic
      instability.
AB  - BACKGROUND: Relative blood volume (RBV) changes during hemodialysis (HD) are
      poorly understood. We wish to define characteristics of RBV profiles at different
      hydration states predictive of hemodynamic instability. METHODS: Thirty patients
      underwent online RBV monitoring during an HD session with intermittent
      ultrafiltration (UF) pulses administered until the onset of hypotension. The RBV
      decay constant (tau) was derived from curve fitting. Linear divergence, the net
      deviation of the RBV curve during UF from predicted linear decay, was computed
      from initial 1-minute slopes. RESULTS: The best correlation with proximity to dry
      weight (PDW) was provided by linear divergence (r = 0.817; P < 0.001), its major
      determinant in multiple regression analysis. Other predictors were RBV at
      initiation of UF pulse, UF pulse volume, and UF decay constant (tau(UF)). These
      parameters were significantly different in UF pulses within 1 kg and 1 kg or
      greater of dry weight. There were no correlations with refill parameters. The
      occurrence of hypotension was not different at RBVs less than 90% (7.4%) or 90%
      or greater (5.3%). tau(UF), linear divergence, RBV at initiation of UF pulse (all
      P < 0.001), and UF decay amplitude (P < 0.01) were different between hypotensive
      and normotensive UF pulses. Hypotension was the only independent predictor of
      tau(UF) (R2 = 0.40; P < 0.001). The only independent predictor of linear
      divergence was PDW (R2 = 0.667; P < 0.001). CONCLUSION: Approaching dry weight,
      the RBV decline during UF switched from exponential to linear decay, probably
      indicating failing vascular refill. Monitoring deviation from linearity may allow
      improved hemodynamic stability and attainment of optimal post-HD weight.

PMID- 12200809
TI  - Diabetes education and care management significantly improve patient outcomes in
      the dialysis unit.
AB  - BACKGROUND: The incidence of diabetes mellitus, particularly type 2, is
      increasing in the general population. Similarly, the incidence of patients with
      diabetes mellitus who develop end-stage renal disease has increased concomitantly
      in the dialysis facility to 44% of patients starting dialysis therapy with
      diabetes mellitus as their primary diagnosis. The aim of this study is to
      determine whether intensive education and care management of diabetes could
      improve glycemic control, alter patient behavior, and reduce complications in the
      setting of the dialysis unit. METHODS: Eighty-three patients were allocated to
      either the control group or study group based on their day of dialysis treatment.
      All patients were followed up for a year. Patients in the study group underwent a
      diabetes education program and were followed up by a care manager who provided
      self-management education, diabetes self-care monitoring/management, motivational
      coaching, and foot checks. RESULTS: The control group baseline foot risk category
      worsened from 2.7 to 3.3 (P < 0.05), whereas it was unchanged in the study group
      (2.2 to 2.0). There were no amputations in the study group versus five
      amputations in the control group (P < 0.05). Ten patients in the control group
      were hospitalized with diabetes- or vascular-related admissions versus one
      patient in the study group (P < 0.002). Hemoglobin A(1c) levels declined from 6.9
      to 6.3 in the study group, whereas results of the control group were unchanged (P
      < 0.005). Diabetes-related quality-of-life scores increased in the study group
      from 76 to 86 (P < 0.001 versus the control group). There was a significant
      improvement in self-management behavior in all six categories evaluated in the
      study group versus the control group. Dialysis centers were recognized by the
      American Diabetes Association to provide diabetes education. CONCLUSION: A
      program of intensive diabetes education and care management in a dialysis unit is
      effective in providing significant improvements in patient outcomes, glycemic
      control, and better quality of life in patients with diabetes mellitus.

PMID- 12200810
TI  - Efficacy of a 1-week course of proton-pump inhibitor-based triple therapy for
      eradicating Helicobacter pylori in patients with and without chronic renal
      failure.
AB  - BACKGROUND: The efficacy of short-course triple therapy for the eradication of
      Helicobacter pylori has been documented in patients with normal renal function.
      We evaluated the efficacy and safety of a 1-week proton-pump inhibitor-based
      triple therapy for H pylori eradication in a prospective study of patients with
      chronic renal failure (CRF). METHODS: Forty-two patients with a creatinine
      clearance (CrCl) less than 30 mL/min/1.73 m2 or serum creatinine level greater
      than 2.26 mg/dL (>200 micromol/L; n = 21; CRF group; 12 patients on dialysis
      therapy) or normal renal function (n = 21; controls) were studied when they had H
      pylori infection on top of peptic ulcer disease (20 patients) or gastritis (22
      patients). The combination of omeprazole, 20 mg twice daily; amoxicillin, 1 g
      twice daily; and clarithromycin, 500 mg twice daily, was administered for 1 week.
      All patients underwent repeated endoscopy 4 weeks later for assessment of
      eradication. Apart from patients on dialysis therapy, all patients had serum
      creatinine levels and CrCls measured 2 and 4 weeks after treatment. RESULTS: All
      except 5 patients (2 patients, CRF group; 3 controls) had successful eradication
      (90.5% versus 85.7%). For patients not on dialysis therapy, serum creatinine
      levels and CrCls remained stable 4 weeks after treatment (serum creatinine, 3.68
      +/- 1.09 versus 3.76 +/- 1.09 mg/dL [325 +/- 96 versus 332 +/- 96 micromol/L]; P
      = not significant [NS]; CrCl, 21.4 +/- 8.3 versus 22.2 +/- 6.9 mL/min/1.73 m2; P
      = NS). CONCLUSION: The 1-week course of proton-pump inhibitor-based triple
      therapy achieved a high eradication rate of H pylori infection in patients with
      CRF, similar to controls with normal renal function. The regimen was well
      tolerated.

PMID- 12200811
TI  - Osteocalcin and myoglobin removal in on-line hemodiafiltration versus low- and
      high-flux hemodialysis.
AB  - BACKGROUND: Removal of medium and large solutes is poor with low-flux (LF-HD) and
      limited with high-flux hemodialysis (HF-HD) and on-line hemodiafiltration (OL
      HDF). In clinical practice, there are few in vivo solute markers. Osteocalcin is
      a protein with a molecular mass of 5,800 daltons, and myoglobin is a large
      molecule with a molecular mass of 17,200 daltons. The aim of this study was to
      evaluate the impact of OL-HDF on in vivo removal of a wide spectrum of solutes
      (urea, creatinine, osteocalcin, beta2-microglobulin, and myoglobin) in comparison
      to LF-HD and HF-HD. METHODS: Twenty-three patients (15 men, 8 women) were
      studied. Every patient underwent three dialysis sessions with routine HD
      parameters. We compared 1.8-m2 polysulfone LF-HD and 1.8-m2 polysulfone HF-HD
      versus OL-HDF. Predialysis and postdialysis solute concentrations were measured.
      The percentage of reduction ratio for each solute was calculated. RESULTS: Mean
      values for predialysis osteocalcin, beta2-microglobulin, and myoglobin were 16.3
      +/- 21 ng/mL, 27.4 +/- 5 mg/L, and 239 +/- 162 ng/mL in LF-HD, respectively. Urea
      and creatinine reduction ratios were similar in LF-HD and HF-HD and only 1.2%
      higher in OL-HDF. Osteocalcin, beta2-microglobulin, and myoglobin reduction
      ratios for LF-HD were negligible. Mean osteocalcin reduction rates were 54.2% +/-
      12% for HF-HD versus 63.5% +/- 9% for OL-HDF (reinfusion volume, 26.8 +/- 5
      L/session; P < 0.01). Mean beta2-microglobulin reduction rates were 60.1% +/- 9%
      for HF-HD versus 75.4% +/- 9% for OL-HDF (P < 0.01). Mean myoglobin reduction
      rates were 24.5% +/- 6% and 62.7% +/- 9% for HF-HD and OL-HDF, respectively (P <
      0.01). CONCLUSION: LF-HD does not seem to remove solutes with a molecular weight
      greater than 5,800 daltons. OL-HDF provides marked enhancement of convection
      volume and enables a significant increase in osteocalcin and beta2-microglobulin
      removal. Myoglobin extraction is nil with LF-HD, very low with HF-HD, and only
      adequate with OL-HDF.

PMID- 12200812
TI  - Effects of erythropoietin and vitamin E-modified membrane on plasma oxidative
      stress markers and anemia of hemodialyzed patients.
AB  - BACKGROUND: Oxidant stress has a pathogenic role in uremic anemia, possibly
      interfering with erythropoietin (EPO) function and red blood cell (RBC) survival.
      Therefore, it is expected that antioxidant therapy might exert a beneficial
      effect on these parameters. METHODS: To test this hypothesis, we investigated
      some oxidant stress indices, anemia levels, and RBC survival in 47 hemodialysis
      (HD) patients randomly assigned to three groups. Patients in groups A (n = l8)
      and B (n = 20) were on dialysis therapy using conventional cellulosic and
      synthetic membranes and were administered high and low doses of recombinant human
      EPO (rHuEPO), respectively. Patients in group C (n = 9) were dialyzed with
      vitamin E-modified membranes (CL-Es) and investigated in a two-step prospective
      study. In step Cl, patients were administered rHuEPO doses similar to those of
      group A. In step C2, rHuEPO doses were reduced to those of group B. As oxidant
      stress markers, we determined in plasma the susceptibility of lipids to undergo
      iron-catalyzed oxidation (reactive oxygen molecules [ROMs] test) and
      malondialdehyde-4-hydroxynonenal (MDA-4HNE), alpha-tocopherol (alpha-T), total
      thiol (-SH), and total antioxidant activity. RBC survival was measured using the
      chromium 51 T/2 technique in 22 patients. RESULTS: Results show that: (1) high
      rHuEPO doses (groups A and C1) were associated with decreased ROM production, low
      alpha-T levels, and slightly increased -SH levels compared with corresponding
      groups on low rHuEPO doses (groups B and C2); (2) treatment with CL-Es (group C)
      increased plasma alpha-T and decreased -SH levels; these data were associated
      with decreased indices of lipid peroxidation, particularly MDA-4HNE 1evels, only
      in patients administered low rHuEPO doses; (3) alpha-T concentration influenced
      RBC survival, which was remarkably decreased in HD patients; patients treated
      with CL-Es showed a better degree of anemia correction; and (4) alpha-T level
      correlated negatively with -SH level and seemed to be independent of the extent
      of peroxidation and oxidizability of plasma lipids. CONCLUSION: Both EPO and CL-E
      can influence plasma antioxidants and, to an extent, lipid peroxidation
      processes. However, this study shows that even in patients treated with low
      rHuEPO doses, RBC survival close to normal and sufficient correction of anemia
      are achieved only when appropriate alpha-T levels are reached.

PMID- 12200813
TI  - Arachidonate cascade, apoptosis, and vitamin E in peripheral blood mononuclear
      cells from hemodialysis patients.
AB  - BACKGROUND: Lipid peroxidation and oxidative stress are enhanced in peripheral
      blood mononuclear cells (PBMCs) from hemodialysis (HD) patients because of
      upregulation of the 5-lipoxygenase pathway of the arachidonate cascade. 5
      Lipoxygenase activity is specifically inhibited by vitamin E both in vitro and in
      vivo regardless of its administration route. METHODS: The effect of arachidonate
      cascade enzymes and vitamin E on oxidative stress and apoptosis was investigated
      in PBMCs from 16 maintenance HD patients treated for at least 6 months with
      cuprammonium rayon membranes in a two-step crossover study: after a 4-week
      treatment with vitamin E-coated cuprammonium rayon membranes and again after a 4
      week treatment with oral vitamin E. Control PBMCs were obtained from 16 healthy
      volunteers. RESULTS: Membrane lipoperoxidation, cellular luminescence, membrane
      fluidity, and leukotriene B(4) content were significantly greater in PBMCs from
      HD patients; lipoxygenase was upregulated, but prostaglandin H synthase (PHS) was
      not affected. Regardless of administration route, vitamin E partially controlled
      lipid peroxidation and oxidative stress through direct inhibition of 5
      lipoxygenase. Cultured PBMCs from HD patients showed a significant increase in
      apoptotic cells compared with controls. Vitamin E markedly reduced cell
      luminescence, membrane fluidity, and apoptosis, whereas the PHS inhibitor
      indomethacin was ineffective. Similar results were obtained with control PBMCs
      induced to apoptosis by hydrogen peroxide. CONCLUSION: Reported data suggest that
      the 5-lipoxygenase branch of the arachidonate cascade is only responsible for
      membrane peroxidation, oxidative stress, and apoptosis of PBMCs of HD patients,
      and administration of vitamin E may be helpful in the control of oxidative stress
      related disease in these subjects.

PMID- 12200814
TI  - Cost analysis of ongoing care of patients with end-stage renal disease: the
      impact of dialysis modality and dialysis access.
AB  - BACKGROUND: Care of patients with end-stage renal disease (ESRD) is important and
      resource intense. To enable ESRD programs to develop strategies for more cost
      efficient care, an accurate estimate of the cost of caring for patients with ESRD
      is needed. METHODS: The objective of our study is to develop an updated and
      accurate itemized description of costs and resources required to treat patients
      with ESRD on dialysis therapy and contrast differences in resources required for
      various dialysis modalities. One hundred sixty-six patients who had been on
      dialysis therapy for longer than 6 months and agreed to enrollment were followed
      up prospectively for 1 year. Detailed information on baseline patient
      characteristics, including comorbidity, was collected. Costs considered included
      those related to outpatient dialysis care, inpatient care, outpatient nondialysis
      care, and physician claims. We also estimated separately the cost of maintaining
      the dialysis access. RESULTS: Overall annual cost of care for in-center,
      satellite, and home/self-care hemodialysis and peritoneal dialysis were US
      $51,252 (95% confidence interval [CI], 47,680 to 54,824), $42,057 (95% CI, 39,523
      to 44,592), $29,961 (95% CI, 21,252 to 38,670), and $26,959 (95% CI, 23,500 to
      30,416), respectively (P < 0.001). After adjustment for the effect of other
      important predictors of cost, such as comorbidity, these differences persisted.
      Among patients treated with hemodialysis, the cost of vascular access-related
      care was lower by more than fivefold for patients who began the study period with
      a functioning native arteriovenous fistula compared with those treated with a
      permanent catheter or synthetic graft (P < 0.001). CONCLUSION: To maximize the
      efficiency with which care is provided to patients with ESRD, dialysis programs
      should encourage the use of home/self-care hemodialysis and peritoneal dialysis.

PMID- 12200815
TI  - Factors influencing erythropoietin compliance in peritoneal dialysis patients.
AB  - BACKGROUND: Peritoneal dialysis patients who manage their own therapy with
      subcutaneous erythropoietin (EPO) may be at risk for noncompliance. The
      objectives of this study were to examine the rate of noncompliance and to
      investigate the factors that are associated with patient noncompliance with the
      prescribed EPO regimen. METHODS: A multiple-choice questionnaire was mailed to
      eligible patients, and a review of pharmacy records was conducted for EPO dates
      of refill. Noncompliance was defined as less than 90% use of the prescribed dose
      either by pharmacy record review or missed injections on the questionnaire.
      RESULTS: Of 55 eligible patients, 54 completed the questionnaire. The overall
      rate of noncompliance was 35%. Patients who were noncompliant were younger (P =
      0.005), had fewer comorbidities (P = 0.050), had been on EPO therapy longer (P =
      0.011), were more likely to have completed postsecondary education (P = 0.011),
      and were more likely to admit to missed peritoneal dialysis exchanges (P =
      0.011). On multiple regression analysis, the independent predictors of
      noncompliance, in order of importance, were missing dialysis exchanges,
      completion of postsecondary education, and younger age. CONCLUSION: These
      findings suggest that noncompliance with EPO injections is relatively common
      among peritoneal dialysis patients. The independent predictors of noncompliance
      were missing dialysis exchanges, completion of postsecondary education, and
      younger age. Further studies are needed to determine if specific interventions
      targeting this group of patients can affect compliance.

PMID- 12200816
TI  - Early evolution of nutritional status and body composition after kidney
      transplantation.
AB  - BACKGROUND: Previous series have dealt with nutritional status after kidney
      transplantation. However, few studies have described the outcome of body
      composition after kidney transplantation. METHODS: A total of 44 cadaver kidney
      transplant recipients (28 men and 16 women) were followed prospectively during
      the first post-transplant year. Biochemical nutritional markers, dietary records,
      anthropometric measurements, and body composition were assessed at kidney
      transplantation and 3, 6, and 12 months later. RESULTS: By the end of the first
      year, serum albumin level was not significantly different from initial values.
      Prealbumin and retinol binding protein decreased from 42.3 +/- 10.2 mg/dL to 30.4
      +/- 6.3 mg/dL and from 1.96 +/- 0.61 g/dL to 0.65 +/- 0.2 g/dL (P < 0.0001).
      Separating patients by gender showed that dietary caloric and protein intake
      increased in women only. At the end of the follow-up period, mean weight change
      was +5.4 kg in women (P = 0.009) and -0.9 kg in men (not significant). Body
      composition analyses showed that in women total fat and lean masses increased
      (+2.1 kg, P = 0.05, and +2.4 kg, P = 0.006), whereas in men total fat mass
      decreased (-1.4 kg, P = 0.04), and total lean mass tended to increase (+0.5 kg,
      not significant). Percentage change in total bone mass was +1.4% in women (not
      significant) and -2.1% in men (P = 0.05). In multivariate analyses, an
      independent impact of female gender on weight gain was observed, although
      increased fat mass was related only to energy intake. Increased total lean mass
      was related to low steroid doses and the absence of acute rejection and delayed
      graft function. Bone loss was related to male gender and high steroid doses.
      CONCLUSION: Changes in body composition during the first year after kidney
      transplantation are modulated by gender, energy intake, steroid doses, the
      occurrence of acute rejection, and delayed graft function.

PMID- 12200817
TI  - Patient survival after renal transplantation III: the effects of statins.
AB  - BACKGROUND: Kidney transplant recipients have high cardiovascular risk and an
      unfavorable cardiovascular risk profile, which frequently includes
      hyperlipidemia. Although the use of HMG-CoA reductase inhibitors (statins) is
      associated with improved survival in the general population, the effects of these
      drugs on the survival of kidney transplant recipients have not been established.
      METHODS: In this study, we determined which factors were associated with the use
      of statins in a population of 1,574 adult, kidney allograft recipients,
      transplanted in one institution. A risk factor analysis of patient survival was
      done with a primary focus on the possible relationship between statin use and
      survival. RESULTS: The percent of patients treated with statins increased
      progressively from 1982 to 1996. Statins were used significantly more often in
      whites (30%) than in blacks (20%, P = 0.001) and in older individuals. These
      differences in statin use were not due to differences in lipid levels among the
      patient groups. As expected, the group of patients treated with statins had
      significantly higher serum lipid levels than untreated patients. Patient survival
      was significantly better in patients treated with statins than in untreated
      patients. That relationship became apparent, however, only after controlling for
      three additional factors: recipient age, transplant year, and serum cholesterol
      levels. In a multivariable Cox survival model, patient survival was associated
      significantly with statin use (hazard ratio [HR] = 0.76; confidence interval
      [CI], 0.6 to 0.96; P = 0.02), recipient age (HR = 1.05; CI, 1.04 to 1.06; P <
      0.0001), and transplant year (HR = 1.05; CI, 1.01 to 1.08; P = 0.001). The serum
      cholesterol level was not associated significantly with patient survival in this
      model, but cholesterol significantly modified the relationship between statin use
      and patient survival. CONCLUSIONS: Renal transplant recipients treated with
      statins have a 24% better survival than patients who do not receive these drugs.

PMID- 12200818
TI  - Fludarabine treatment of cryoglobulinemic glomerulonephritis.
AB  - Three patients (one hepatitis C positive) presented with renal insufficiency and
      nephrotic-range proteinuria resulting from mixed cryoglobulinemia and
      glomerulonephritis. All three patients received two to four cycles of intravenous
      fludarabine (each cycle consisted of 25 to 50 mg/d for 4 to 5 days). All patients
      responded to therapy with a decrease in proteinuria, increase in serum albumin,
      and decrease in serum creatinine. This response was evident by 2 months and
      persisted for 2 to 5 years. In two patients, this response was accompanied by
      disappearance of cryoglobulins, at least transiently. One patient developed
      tuberculosis with neutropenia. Transient blindness and neutropenia were seen in
      another patient. These results suggest that fludarabine may be a useful treatment
      in cryoglobulinemia with glomerulonephritis, although its use may be accompanied
      by side effects.

PMID- 12200819
TI  - Anti-glomerular basement membrane nephritis and bullous pemphigoid caused by
      distinct anti-alpha 3(IV)NC1 and anti-BP180 antibodies in a patient with Crohn's
      disease.
AB  - BACKGROUND: Anti-glomerular basement membrane (GBM) nephritis is a rare disease
      induced by antibodies directed against alpha3(IV)NC1, the Goodpasture antigen. We
      report a patient with Crohn's disease who developed anti-GBM nephritis and the
      skin blistering disorder bullous pemphigoid, owing to distinct autoantibodies.
      METHODS: Frozen sections of skin and kidney biopsies were incubated with antisera
      specific for human IgG, IgA, IgM, fibrin, and C3. Reactivity of the patient's
      serum with GBM antigens was studied by Western blot using bovine solubilized type
      IV collagen and by enzyme-linked immunosorbent assays using alpha1(IV),
      alpha3(IV), and alpha5(IV)NC1 recombinant proteins. Reactivity studies against
      skin antigens were done by Western blot using human keratinocyte and dermal
      extracts and three recombinant forms of the bullous pemphigoid antigen180 (BP180,
      also called BPAG2 or type XVII collagen). The patient's serum was affinity
      fractionated on a (IV)NC1 column, and the bound and unbound fractions were
      analyzed for their reactivity against GBM and skin antigens. RESULTS: The patient
      had deposits of IgG along the GBM and the epidermal basement membrane zone.
      Circulating IgG antibodies against alpha3(IV)NC1 were detected. The patient's
      autoantibodies immunoblotted the intracellular domain but not the extracellular
      domain of BP180. Reactivity of the patient's IgG with BP180 was found only in the
      unbound fraction of the serum. CONCLUSION: The simultaneous development of a rare
      renal and skin autoimmune disorder, resulting from non-cross-reactive
      autoantibodies, suggests that a common triggering event could be responsible for
      the autoimmune injury.

PMID- 12200820
TI  - Nephrotoxic acute renal failure in a renal transplant patient with recurrent
      lymphocele treated with povidone-iodine irrigation.
AB  - Povidone-iodine sclerosis has been suggested in the literature as a safe and
      effective treatment for post-renal transplant lymphoceles. No significant
      complications of this method have been described. We report on a kidney allograft
      recipient with recurrent lymphoceles treated with povidone-iodine instillations
      who developed acute renal failure secondary to iodine intoxication. Four days
      after the beginning of the povidone-iodine irrigations, metabolic acidosis was
      present, and renal function started to deteriorate. After a few days, despite the
      suspension of irrigations, the patient developed oliguria, and dialysis was
      needed. A renal biopsy was performed, and intense acute tubular necrosis was the
      only relevant finding. The lymphocele was corrected surgically, and the patient
      eventually recovered. As has been described in other settings, povidone-iodine
      instillation for the treatment of post-renal transplant lymphoceles may lead to
      iodine kidney toxicity and acute renal failure.

PMID- 12200821
TI  - Isolated renal giant cell arteritis.
AB  - Giant cell arteritis, which most commonly affects the temporal arteries, may
      involve intrarenal vessels and may be associated with a variety of renal lesions,
      including necrotizing arteritis, necrotizing glomerulonephritis, granulomatous
      glomerulonephritis, and membranous glomerulopathy. Isolated giant cell arteritis
      of the kidney is a rare cause of renal failure. We report a case of a previously
      healthy 54-year-old white woman who presented with nonoliguric renal failure and
      a 4-week history of persistent low-grade fever associated with diffuse mild
      myalgias. She had no history of previous renal or neurologic disease and denied
      any headaches or visual disturbances. Antinuclear antibody and antineutrophilic
      cytoplasmic antibody were negative. Renal biopsy revealed noncaseating
      granulomatous infiltration of arterial and arteriolar walls, a patchy mononuclear
      cell interstitial infiltrate, and no significant glomerular changes. Treatment
      with prednisone resulted in dramatic improvement of renal function.

PMID- 12200822
TI  - Preaching and practice: evidence-based medicine and the accountability of
      nephrologists within the health care system. The implications of the findings of
      the cost-saving potential of subcutaneous versus intravenous epoetin therapy.

PMID- 12200823
TI  - High-dose ACE inhibition: can it improve renoprotection?

PMID- 12200824
TI  - Acute renal failure in a renal allograft recipient treated with intravenous
      immunoglobulin.

PMID- 12200825
TI  - Reversal of pulmonary hypertension after ligation of a brachiocephalic
      arteriovenous fistula.
AB  - The arteriovenous (AV) fistula is the access method of choice for long-term
      hemodialysis according to DOQI guidelines. Among the recognized complications of
      upper extremity AV fistulae fashioned for hemodialysis are infection, aneurysm
      formation, and high-output left ventricular failure. We describe a novel
      cardiopulmonary complication--secondary pulmonary hypertension resulting from an
      aneurysmal brachiocephalic AV fistula. The clinical presentation, investigation,
      management, and pathophysiology of this complication are discussed.

PMID- 12200826
TI  - Fibrillary glomerulonephritis: early diagnosis associated with steroid
      responsiveness.
AB  - Patients with fibrillary glomerulonephritis usually present with nephrotic
      proteinuria, microscopic hematuria, impaired renal function, and hypertension;
      50% develop end-stage renal disease within a few years. There is no known
      effective therapy for fibrillary glomerulonephritis. We describe three patients
      with biopsy-proven fibrillary glomerulonephritis, in whom pathognomonic fibrillar
      deposits of 20-nm diameter were seen by electron microscopy. All patients had
      nephrotic syndrome and normal renal function at the time of diagnosis. They were
      treated initially with prednisone, 1 mg/kg body weight, then tapered individually
      according to the clinical course. Additional therapy consisted of an angiotensin
      converting enzyme inhibitor and diuretics. Proteinuria disappeared in two of
      three patients after 9 and 12 months of therapy. In one patient, proteinuria was
      reduced from 7.49 mg/mg creatinine to 0.63 mg/mg creatinine after 6 months of
      treatment. The kidney function remained normal in all three cases. Two patients
      are now free of steroid therapy for 9 and 6 months. They show no signs of
      recurrence of kidney disease and have normal renal function without significant
      proteinuria. Steroid therapy in patients with biopsy-proven fibrillary
      glomerulonephritis, starting with prednisone, 1 mg/kg body weight, and tapered
      individually according to the clinical course, is a promising strategy. Early
      start of treatment in patients with preserved renal function seems to be crucial
      for a favorable outcome.

PMID- 12200827
TI  - Collapsing glomerulopathy: a cause of noncardiogenic pulmonary edema.
AB  - Collapsing glomerulopathy is a pathologic diagnosis characterized by obliteration
      of glomerular capillary lumina, seen most commonly as a primary glomerular
      disease in young black men. A secondary form with almost identical pathologic
      features is described in association with human immunodeficiency virus infection.
      The disease is characterized by heavy proteinuria with variable renal
      insufficiency at the onset followed by rapid progression to end-stage renal
      disease with no documented effective therapy. We describe a patient who presented
      with systemic manifestations, including fever, acute renal failure with massive
      proteinuria, and noncardiogenic pulmonary edema. Renal biopsy showed classic
      collapsing glomerulopathy. All known causes of noncardiogenic pulmonary edema
      were ruled out. The pulmonary syndrome resolved, but the renal disease progressed
      to end-stage renal disease. We propose consideration of collapsing glomerulopathy
      in the differential diagnosis of any patient presenting with a multisystem
      disease including acute renal failure and pulmonary edema.

PMID- 12200828
TI  - Renal artery dissection after blunt abdominal trauma: a rare cause of acute
      cortical necrosis.
AB  - Renal artery injury is an uncommon complication of blunt abdominal trauma. We
      present a case of a 19-year-old man who developed acute cortical necrosis in a
      congenital single kidney after a motorcycle accident. On initial presentation, he
      had signs of splenic injury and required immediate laparotomy and splenectomy.
      His renal function deteriorated, and he became dialysis dependent. Computed
      tomography followed by percutaneous angiography showed a dissection of a single
      renal artery causing the formation of a large pseudoaneurysm. A second angiogram
      showed an increase in the size of the pseudoaneurysm. We performed a laparotomy
      and attempted in situ vein graft repair of the renal artery. A wedge biopsy
      specimen taken at laparotomy revealed acute cortical necrosis, and plain
      radiographs showed cortical calcification. Renal artery dissection and
      pseudoaneurysm formation are rare events after blunt trauma. Iatrogenic damage is
      the most common cause of pseudoaneurysm. Traumatic pseudoaneurysms have a poor
      prognosis without prompt surgical intervention. Renal arterial damage may occur
      after blunt trauma, and early imaging and intervention are essential to salvage
      renal function.

PMID- 12200829
TI  - Isopropyl alcohol intoxication: a diagnostic challenge.
AB  - Isopropyl alcohol (IPA) is an ingredient of commonly used household solutions.
      Accidental and suicidal ingestion of IPA sometimes can be fatal if it goes
      unrecognized and untreated. There are few published reports on IPA intoxication.
      We describe a case of repeated IPA ingestion in a single individual, followed by
      a review of the literature on the subject. The differential diagnosis, diagnostic
      pitfalls, and therapeutic interventions in patients with IPA intoxications are
      discussed.

PMID- 12200830
TI  - Elimination of ingredients effect to improve the detection of anti HIV-1 p24
      antibody in human serum using SPR apparatus.
AB  - Highly sensitive detection of proteins in serum becomes difficult in some cases
      during surface plasmon resonance (SPR) measurements, because some ingredients in
      the serum hugely enhance non-specific reactions on the sensing chip of SPR. It is
      well recognized that the antibody against core protein p24 of HIV in serum is one
      of the most important proteins in the accurate diagnosis of infection with HIV.
      In this study, we could attain the accurate detection of anti p24 antibody in
      human serum by eliminating the serious effects of the ingredients in serum on the
      measurement of SPR by employing these procedures: 1) blocking the gold surface of
      the sensing chip with human serum and 2) heating the serum sample at 56 degrees C
      for 30 min. Without these treatments, the signal of SPR was considerably
      suppressed on the measurements of the anti p24 antibody which contained human
      serum, making the accurate detection difficult. However, with introducing the
      above two treatments, the sensing of anti p24 antibody in human serum was
      improved, while a small non-specific reaction was still observed. By removing the
      non-specific reaction caused by the ingredients in the serum, we could accurately
      measure the antibody for p24 in human serum sample over the range from 1 to 20
      micrograms/ml.

PMID- 12200831
TI  - Quantitative measurement of 17 beta-estradiol and estriol in river water by time
      resolved fluoroimmunoassay.
AB  - A sensitive method for detecting 17 beta-estradiol (E2) and estriol (E3) in river
      water has been developed, based on the time-resolved fluoroimmunoassay by using a
      fluorescent europium chelate label, 4,4'-bis(1",1",1",2",2",3",3"-heptafluoro
      4",6"-hexanedion-6"-yl)- chlorosulfo-o-terphenyl (BHHCT)-Eu3+. In the E2 assay,
      microtiter plates were coated with the E2-bovine serum albumin (BSA) conjugate.
      The anti-17 beta-estradiol antibody, the biotinylated goat anti-rabbit IgG
      antibody and the BHHCT-Eu3+ labeled streptavidin (SA)-BSA conjugate were used. In
      the E3 assay, the goat anti-rabbit IgG antibody was coated on a microtiter plate.
      The anti-estriol antibody and the BHHCT-Eu3+ labeled E3-BSA conjugate were used.
      The detection limits for E2 and E3 were 2.3 pg/ml and 4.3 pg/ml, respectively,
      and the analytical recoveries were 95-120%. Quantitative measurement of estrogens
      in river water was carried out for Kanda River (Tokyo, Japan) by using the
      method. The E2 and E3 levels were 32 pg/ml and 5.5 pg/ml, respectively. The
      detection limits of the present method are in the same orders of magnitude as
      those of ELISA for E2, and are 1-2 orders of magnitude better for E3.

PMID- 12200832
TI  - A 9,10-anthraquinone derivative having two propenyl arms as a neutral ionophore
      for highly selective and sensitive membrane sensors for copper(II) ion.
AB  - New polymeric membrane (PME) and coated graphite (CGE) copper(II)-selective
      electrodes based on 1-hydroxy-2-(prop-2'-enyl)-4-(prop-2'-enyloxy)-9,10
      anthraquinone were prepared. The electrodes reveal linear emf-pCu2+ responses
      over wide concentration ranges (1.0 x 10(-5)-1.0 x 10(-1) M with a slope of 27.3
      mV decade-1 for PME and 8.0 x 10(-8)-5.0 x 10(-2) M with a slope of 29.1 mV
      decade-1 for CGE) and very low limits of detection (8.0 x 10(-6) M for PME and
      5.0 x 10(-8) M for CGE). The potentiometric response is independent of the pH of
      the test solution in the pH range 3.0-6.0. The proposed electrodes possess very
      good selectivities over a wide variety of other cations, including alkali,
      alkaline earth, transition and heavy metal ions, the selectivity coefficients for
      the CGE being much improved over those for the PME. The electrodes were used as
      indicator electrodes in the potentiometric titration of Cu2+ and in the recovery
      of copper ions from wastewater.

PMID- 12200833
TI  - Silver-selective sensor using an electrode-separated piezoelectric quartz crystal
      modified with a chitosan derivative.
AB  - Silver(I) adsorbed selectively onto a quartz plate modified with N-(2
      pyridylmethyl)chitosan in an ammonium chloride buffer solution containing EDTA,
      and the frequency of the quartz plate increased. It was supposed that the
      increasing frequency was caused by the desorption of adsorbed water on the
      chitosan derivative, which was induced from the reaction of silver(I) with the
      chitosan derivative. The concentration of the buffer, pH, temperature,
      conductivity and eluent affected the frequency shift resulting from the
      adsorption of silver(I). The frequency decreased at a conductivity lower than 2.2
      mS/cm, and increased with increasing conductivity above this value. The frequency
      shifts caused by the adsorption of silver(I) were proportional to the
      concentration over the range 10-80 nM of silver(I), and the correlation
      coefficient was 0.9969. The detection limit and the relative standard deviation
      at 50 nM for five times were 6 nM and 3.4%, respectively. The proposed method was
      simple while showing higher sensitivity and selectivity.

PMID- 12200834
TI  - Determination of SCN- in urine and saliva of smokers and non-smokers by SCN(-)
      selective polymeric membrane containing a nickel(II)-azamacrocycle complex coated
      on a graphite electrode.
AB  - The construction, performance characteristics, and application of a novel
      polymeric membrane coated on a graphite electrode with unique selectivity towards
      SCN- are reported. The electrode was prepared by incorporating Ni(II)
      2,2,4,9,9,11-hexamethyltetraazacyclotetradecanediene perchlorate into a
      plasticized poly(vinyl chloride) membrane. The influences of membrane
      composition, pH and foreign ions were investigated. The electrode displays a near
      Nernstian slope (-57.8 mV decade-1) over a wide concentration range of 1 x 10(-7)
      1 x 10(-1) M of SCN- ion. The electrode has a detection limit of 4.8 x 10(-8) M
      (2.8 ng/cm3) SCN- and shows response times of about 15 s and 120 s for low to
      high and high to low concentration sequences, respectively. The proposed sensor
      shows high selectivity towards SCN- over several common organic and inorganic
      anions. The electrode revealed a great enhancement in selectivity coefficients
      and detection limit for SCN-, in comparison with the previously reported
      electrodes. It was successfully applied to the direct determination of SCN- in
      milk and biological samples, and as an indicator electrode in titration of Ag+
      ions with thiocyanate.

PMID- 12200835
TI  - Determination of alpha hydroxy acids in fruits by capillary electrophoresis.
AB  - Alpha hydroxy acids, malic acid, citric acid, tartaric acid, glycolic acid and
      lactic acid, were analyzed simultaneously using capillary electrophoresis with
      direct UV detection at 200 nm. The separation was carried out with uncoated fused
      silica (50 cm x 50 microns i.d.), pressure injection at 15 psi s and operated at 
      15 kV potential. The separation buffers were prepared with 180 mM Na2HPO4, 1 mM
      cetyltrimethylammonium bromide and 15% (v/v) methanol and adjusted to pH 7.2 by
      phosphoric acid. Validation was performed for citric acid and malic acid. The
      obtained parameters were adequate and the limits of detection were 2.5 and 5
      micrograms ml-1 for citric acid and malic acid, respectively. AHAs from natural
      fruit juices (orange and grape) were determined and measured with this method.

PMID- 12200836
TI  - Enrichment and determination of zinc by high-speed countercurrent chromatography.
AB  - The capability of high-speed countercurrent chromatography (HSCCC) has been
      investigated for enrichment and determination of metal ions at trace levels.
      Separation of selected divalent metal ions was performed using a small coiled
      column. A hexane solution of 2-ethylhexylphosphonic acid mono-2-ethylhexyl ester
      (EHPA) was employed as the stationary phase. Loaded divalent metal ions such as
      Ni, Co, Cu, and Zn were chromatographically eluted in the order of increasing
      extractability by passing a mobile phase buffered at a desired pH. Individual
      metal ions showed good linearity between concentrations and chromatographic peak
      areas of the absorbance, as detected by postcolumn reaction with 4-(2
      pyridylazo)resorcinol (PAR). Metal ions enriched into the stationary phase from a
      sample solution were separated into individual metal ions. The trace quantity of
      zinc in natural mineral water was determined by enrichment separation through an
      HSCCC column.

PMID- 12200837
TI  - Liquid chromatographic determination of alcohols in food and beverages with
      indirect polarimetric detection using a beta-cyclodextrin mobile phase.
AB  - An indirect polarimetric detection method for the determination of alcohols has
      been proposed in liquid chromatography (LC). Optically active mobile-phase
      additives, such as beta-cyclodextrin (beta-CD), could be used to visualize
      optically inactive alcohols in reversed-phase LC. The visualization of alcohols
      is based on a perturbation of the partition of beta-CD caused by the alcohols.
      The detection limits of the present system at a signal-to-noise ratio of 3 were
      0.031, 0.019, 0.018, 0.013, 0.011, 0.008 and 0.008% (v/v) for ethanol, 2
      propanol, 1-propanol, 2-methyl-2-propanol, 2-butanol, 2-methyl-1-propanol and 1
      butanol, respectively. The method was successfully applied to the determination
      of ethanol present in food and beverage samples.

PMID- 12200838
TI  - Analysis of photodecomposition of gaseous chlorobenzene by KrF excimer laser.
AB  - Gaseous monochlorobenzene was irradiated with KrF excimer laser (248 nm) under
      reduced pressure. The photodecomposition was an apparent first order reaction.
      When the system contained no additive gas, the photolysis was found to give
      benzene (conversion yield: 49%) in the gas phase and many unidentified products
      in the solid phase. On the other hand, in the presence of oxygen, carbon dioxide
      (10%), carbon monoxide (16%), hydrogen chloride (52%) and acetylene (2%) are
      produced and the peaks shown on the gas chromatogram of the solid phase were
      effectively suppressed.

PMID- 12200839
TI  - Extractive spectrophotometric determination of tungsten(VI) in alloy steels using
      ethopropazine hydrochloride.
AB  - Ethopropazine hydrochloride (EPH) has been proposed as a sensitive reagent for
      the spectrophotometric determination of tungsten(VI). The method is based on the
      formation of a chloroform-soluble yellow-colored ternary complex by the
      interaction of EPH and thiocyanate with tungsten(V). The complex exhibits the
      absorption maximum at 404 nm with Sandell's sensitivity value of 20.03 ng cm-2.
      The complex obeyed Beer's law in the concentration range of 1-15 micrograms ml-1
      with an optimum concentration range of 2.3-12.9 micrograms ml-1. The effects of
      foreign ions in the determination of tungsten(VI) were investigated. The method
      has also been successfully applied to the analysis of alloy steels.

PMID- 12200840
TI  - Determination of iron, manganese and zinc in water samples by flame atomic
      absorption spectrophotometry after preconcentration with solid-phase extraction
      onto Ambersorb 572.
AB  - A solid-phase extraction method for the preconcentration of Fe, Mn and Zn on a
      column containing Ambersorb 572 has been developed, and the determination of Fe,
      Mn and Zn in water using a flame atomic absorption spectrophotometer (FAAS) has
      been performed. The optimum preconcentration parameters of the procedure have
      been determined. The effect of the pH, complexing agent, amount of adsorbent,
      flow rate, concentration and volume of the elution solution and interfering ions
      on the recovery of the analytes were investigated. The recoveries of Fe, Mn and
      Zn were 99 +/- 3%, 98 +/- 3% and 99 +/- 3% at the 95% confidence level,
      respectively, under the optimum conditions. Fe, Mn and Zn were preconcentrated up
      to 50, 100, 200, respectively. The limits of detection of Fe, Mn and Zn are 2.5,
      0.68 and 0.24 micrograms l-1, respectively. The adsorption capacity of the
      adsorbent was found to be 10.9, 13.1 and 21.5 mg g-1 for Fe, Mn and Zn,
      respectively. The method has been applied to the determination of these metal
      ions in tap-water and river-water samples. The precision and the accuracy of the
      method is very good. The relative standard deviation and the relative error are
      lower than 4%.

PMID- 12200841
TI  - Application of internal standardization to rapid coprecipitation technique using
      lanthanum phosphate for flame atomic absorption spectrometric determination of
      iron and lead.
AB  - By applying an internal standardization, we could use a rapid coprecipitation
      technique using lanthanum phosphate as a coprecipitant for preconcentration of
      iron(III) and lead in their flame atomic absorption spectrometric determination.
      Indium as an internal standard was added to the initial sample solution together
      with lanthanum and phosphoric acid; the coprecipitation of iron(III) and lead was
      then carried out at pH about 3. After measuring the atomic absorbances of iron,
      lead, and indium in the final sample solution, we determined the contents of
      iron(III) and lead in the original sample solution by using the internal
      standardization with indium. In this method, complete collection of the
      precipitate was not required after the coprecipitation of iron(III), lead, and
      indium, because the ratio of the recovery of iron(III) or lead to that of indium
      was almost constant regardless of the recovery of the precipitate. This method
      was simple and rapid, and was available for the determination of 2-300 micrograms
      L-1 of iron(III) and 5-400 micrograms L-1 of lead in some water samples.

PMID- 12200842
TI  - X-ray absorption spectral studies on the anion-selectivity of a ruthenium(II)
      polypyridine complex-impregnated polymer ultrathin film.
AB  - The anion-selectivity of the surface of a polymer ultrathin film incorporating an
      amphiphilic ruthenium(II) polypyridine complex with diperchlorate was examined
      using X-ray absorption spectroscopy with the total electron-yield method. The
      adsorbed species on the film surface were found to depend on the chemical
      composition in water where the film was prepared. By combining the X-ray
      absorption spectra with a molecular-orbital calculation, the molar ratio
      (MClO4/MRu) between the ClO4- ions and the Ru head group on the film surface
      could be semi-quantitatively analyzed; it was 0.88 for a film prepared on fresh
      water, and 1.4 for one prepared on old water.

PMID- 12200843
TI  - In-situ FTIR spectroelectrochemical study of dopamine at a glassy carbon
      electrode in a neutral solution.

PMID- 12200844
TI  - A novel hydrogen peroxide sensor based on specifically interacted silver
      dispersed sol-gel derived ceramic composite electrode.

PMID- 12200845
TI  - Direct electron transfer of glucose oxidase molecules adsorbed onto carbon
      nanotube powder microelectrode.

PMID- 12200846
TI  - Preparation of an organic acid-imprinted resin by a surface imprinting method.

PMID- 12200847
TI  - Simultaneous determination of nitrite and nitrate ions in culture media by ion
      interaction chromatography.

PMID- 12200848
TI  - Spectrofluorometric determination of catechins with 1,2-diphenylethylenediamine.

PMID- 12200849
TI  - Spectrophotometric determination of gallium(III) with rutin.

PMID- 12200850
TI  - Crystal structure of bis((N,N'-dimethylformamide)(mu-formato)[mu
      bis(salicylidene)-1,3- propanediaminato]nickel(II))cobalt(II)monohydrate.

PMID- 12200851
TI  - Crystal structure of trans-2,6-bis(n-propylamino)-2,4,4,6,8,8
      hexapyrrolidinocyclo-2 lambda 5, 4 lambda 5, 6 lambda 5, 8 lambda 5
      tetraphosphazatetraene.

PMID- 12200853
TI  - Crystal structure of 1:1 complex crystal between 4-(3-methoxybenzyloxy)-6-methyl
      2-pyrone and maleimide.

PMID- 12200852
TI  - Crystal structure and synthesis of 17 alpha-acetoxy-4-bromopregn-4-ene-3,20
      dione.

PMID- 12200854
TI  - Crystal structure of a unique sodium distorted linkage in diclofenac sodium
      pentahydrate.

PMID- 12200855
TI  - [Functional analysis of the human T-type calcium channel alpha 1H subunit gene in
      cellular proliferation].
AB  - An increase in the functional expression of the T-type calcium (Ca) channel
      previously has been proposed to be associated with vascular smooth muscle cell
      proliferation although direct evidence for the channel causing these effects
      remains to be demonstrated. In this study, we provide evidence that stable over
      expression of the alpha 1H subunit of the T-type Ca channel (CACNA1H) in HEK-293
      cells confers a significant growth advantage. Over-expression of the alpha 1H
      subunit of the T-channel was confirmed in stable transfects by RT-PCR analysis
      using specific primer pairs and also by electrophysiology. Growth curve assays
      showed population doubling time for alpha 1H stable transfects was 14.0 +/- 0.4
      h, whereas control cultures had a population doubling time of 22.1 +/- 1.1 h (n =
      3, P < 0.05). In addition, total cell numbers significantly increased in stable
      transfects at all time points investigated from 48-120 h after plating (5 x 10(3)
      cells/well) compared with control cultures. Consistent with these findings flow
      cytometry showed that 53.9% of control cells were in G1, 34.5% in S and 11.6% in
      G2/M whereas alpha 1H transfectants displayed 45.6% of cells in G1, 44.6% in S
      and 9.8% in G2/M. Finally, the Western blotting results verified that the levels
      of protein expression of CDK2, cyclin A and cyclin E were relatively high in
      alpha 1H transfectants compared to control cultures. Our results demonstrate that
      the T-type Ca channel provides a growth advantage to HEK-293 cells when stably
      expressed and that it probably exerts these effects via control of the G1/S cell
      cycle mechanism.

PMID- 12200856
TI  - [The analysis of the surnames and intermarriages of the suburbanites of
      Shanghai].
AB  - The origins of the suburban native of shanghai are varied. With the methods of
      correlation analysis and principal analysis, we random sampled the surnames of 13
      villages and towns located in the districts of Shanghai, and found that Jading,
      Pudong, Nanhui and the east part of Fengxian make up the group of northeast part,
      while Jinshan, Songjiang, Qingpu and Chongming make up a completely different one
      from the other. The surnames of Nanxiang's origin are complex, while Maqiao and
      Jinhui's are of special kind. The surnames recorded in pedigree have apparent
      correlation with the modern ones. Moreover, the surnames of northeast part are
      mainly derived from the areas north to Yangtze River, but those of southwest part
      come from the areas south to Yangtze River. This explains that the origins of the
      two districts' throng may be different. The residents of the northeast part,
      which formed land comparatively recent, probably came from north areas after Tang
      and Song periods, while those of southeast part came from other northern areas.
      The residents of shell bar districts such as Maqiao and Jinhui have inherited
      relation with the culture of remote antiquities of Maqia. The contributing
      factors of surname are diversified. By researching into the scope of
      intermarriage of 20th century in Jinhui, we found that before 70's, the
      intermarriage radius was fixed in 5 kilometers because of match maker custom; in
      the 70's & 80's, unrestrained love reduced the intermarriage radius into same
      village about 3 kilometers; after in 90's, the intermarry radius expand to every
      province because of the rapid social and economic development. The intermarriage
      scope and consanguinity natural diffuseness can stand for the situations in
      shanghai and in large parts of south China. The assimilation of adjacent villages
      under matchmaker custom takes over 2000 years, while takes over 7000 years under
      unrestrained love. We can see that the impact of the natural diffuseness is
      rather weak, and the mixed living of emigrants is the main factor. The history of
      every colony's adjacent living is far shorter than that of assimilation. So there
      is almost no mixed race in this period. The most parts of south China's
      situations should be similar. The broken of traditional intermarry suggests us
      that the auto-disappear speed of abundant genetic resource is high. It is now the
      most pressure time to gather and research our genetic resource.

PMID- 12200857
TI  - [Mapping quantitative trait loci for fat deposition in carcass in pigs].
AB  - One of the major determining factors in the price of market hogs today is backfat
      depth. Therefore, identification of regions of the genome affecting this trait is
      necessary. Gene-mapping technologies have provided scientists the necessary
      reagents to conduct genomewide searches for genes affecting any phenotype
      determined in part by the genetic makeup of the animal. Over the past few years,
      several experimental crosses have been used to detect quantitative triat loci
      (QTL) for fatness and meat quality traits in pigs. In an intercross between Large
      White and Meishan pigs, 81 F2 progenies in 1998 were slaughtered and phenotyped
      for fat deposite traits. F2 animals, their parents, and their grandparents were
      typed for molecular markers covering chromosomes (SSC) 1,2,3,4,6 and 7, since
      previous studies had revealed QTL affecting fatness traits on these chromosomes.
      Linear model and least square analyses were used for mapping these traits.
      Furthermore, a QTL accounting for imprinting effects was used. A total of 14 QTL
      at chromosome-wide level were detected on SSC1, 3-4, 6 and 7 for 12 fatness
      traits. There were evidences for imprinting effects on SSC7 for four traits at 60
      cM and nearby. There were QTL for average backfat thickness (BFT) on SSC1, 4 and
      7. Among them, BFT QTL on SSC1 and 7 may be the common locus for Sus scrofa. QTL
      for internal fat percentage was on SSC7 and QTL for average sidefat on SSC6.

PMID- 12200858
TI  - [Polymorphism analysis of the exon 2 of SLA-DQB gene in Xiao Meishan, Zhong
      Meishan and Yorkshire pigs with PCR-RFLP].
AB  - SLA is an important genetic region which influences disease resistance in pigs,
      and the gene family is one of important candidates for disease resistance and
      susceptibility. In present research the exon 2 of SLA-DQB gene was amplified and
      a uniform fragment of 273 bp was obtained in Xiao Meishan, Zhong Meishan and
      Yorkshire Pigs. The 273 bp PCR product was digested with restriction endonuclease
      Rsa I and genetic Polymorphism was investigated with PCR-RFLP (restriction
      fragment length polymorphism). Polymorphic sites were detected at base position
      11, 94 and 124 of the exon 2 of SLA-DQB gene. There were two kinds of genotypes
      in Xiao Meishan pigs, 246 bp/27 bp(AA) and 132 bp/84 bp/30 bp/27 bp(BB), the
      frequencies of genotype AA and BB are 0.571, and 0.439 respectively. Four kinds
      of genotypes were found in Zhong Meishan pigs, 246 bp/27 bp (AA), 132 bp/84 bp/30
      bp/27 bp(BB), 132 bp/114 bp/27 bp(CC) and 246 bp/132 bp/84 bp/30 bp/27 bp(AB),
      their frequencies are 0.037, 0.593, 0.037 and 0.333 respectively. Five kinds of
      genotypes were found in Yorkshire pigs, 246 bp/27 bp(AA), 246 bp/132 bp/114 bp/27
      bp(AC), 132 bp/114 bp/27 bp(CC), 246 bp/132 bp/84 bp/30 bp/27 bp(AB) and 273
      bp/246 bp/27 bp(AD), the frequencies of five genotypes are 0.467, 0.300, 0.100,
      0.100 and 0.033 respectively. Statistical results indicated that there is no
      favorable allele in Xiao Meishan pig breed; B is the favorable allele in Zhong
      Meishan and its gene frequency is 0.759; while in Yorkshire pigs A is the
      favorable allele and its gene frequency is 0.683. Four alleles (A, B, C and D)
      were found in SLA-DQB locus among three pig breeds; The results of chi 2 showed
      that four alleles of this locus fit with Hardy-Weinberg equilibrium. The research
      showed that conservation of Chinese local pig breeds is necessary in order to
      protect our rich genetic resources and make use of them in the future.

PMID- 12200859
TI  - [Genetic effects on grain shape traits of indica black pericarp rice and their
      genetic correlations with main mineral element contents in grains].
AB  - Complete diallel crosses with 7 varieties of indica black pericarp rice were
      conducted to analyze the genetic effects on grain shape traits such as 100-grain
      weight, grain length, grain width and length/width and their genetic correlations
      with main mineral elements of Fe, Zn, Mn and P contents in kernels of parents and
      their F1s and F2s, by using the full genetic model including seed, cytoplasmic
      and maternal effects on quantitative traits of seeds in cereal crops. The results
      indicated that the grain shape traits were controlled by seed direct genetic
      effects, maternal genetic effects as well as by cytoplasmic effects. The seed
      direct genetic effects were more important than the maternal genetic effects for
      grain shape traits, and seed direct additive effects constituted a major part of
      their genetic effects. The narrow heritabilities of seed direct effects were high
      for 100-grain weight, grain width and grain length/grain width, while those of
      seed and maternal effects were intermediate for grain length. Therefore, more
      attention should be paid to the single seed selection on the 100-grain weight,
      grain width and grain length/grain width in early generations of hybrid
      offspring, while in the case of grain length, attention should be paid to single
      plant selection and single seed selection in late generations. The results also
      showed that there existed significant genetic correlations of seed direct
      additive, seed direct dominance, cytoplasm, maternal additive and maternal
      dominance between most of grain shape traits such as 100-grain weight, grain
      length, grain width, grain length/grain width and main mineral elements of Fe,
      Zn, Mn and P contents in grains. The improvement for nutrient quality traits of
      main mineral elements Fe, Zn, Mn and P contents in indica black pericarp rice
      could be realized by the indirect selection of grain shape traits in speciality
      rice quality breeding.

PMID- 12200860
TI  - [Analysis of leaf proteins of Zidao male-sterile line by 2D-PAGE].
AB  - Using two-dimensional gel electrophoresis (2D-PAGE), seven protein maps of leaf
      protein were obtained and analyzed. The results showed that the protein maps of
      four male sterile lines, Zidao male sterile line, Yebai male sterile line,
      Honglian male sterile line and Maxie male sterile line, were different from each
      other; The maps of Zidao male sterile line and maintainer of trefoil stage were
      similar and so did the maps of stooling stage; Either the sterile line map of two
      stages or the maintainer's was different. It can be deduced that the difference
      of maps of two stages might relate to male sterility of Zidao male sterile line.

PMID- 12200861
TI  - [Chromosome mapping of the S-b locus for F1 pollen sterility in cultivated rice
      (Oryza sativa L.) with RAPD markers].
AB  - S-b is one locus for F1 pollen sterility in cultivated rice (Oryza sativa L.),
      and the genotype of Taichung 65 (abridged as T65) is Sj/Sj, while its isogenic
      line, TISL2 is Si/Si at this locus. The results of pollen fertility analysis
      showed that the pollen of T65 and TISL2 were fertile, but the F1 plant from T65 x
      TISL2 produced only 40.6% fertile pollens, and the type of sterile pollen was
      stainable abortive. In F2 population from the cross T65 x TISL2 and BC1F1
      population from the cross T65/TISL2/T65, the individuals could be classified into
      plants with normal pollens and plants with semi-sterile pollens, and the ratio of
      number of these two types of plants agreed well with the Mendel segregation ratio
      in 1:1. A total of 53 fertile F2 plants were testcrossed with T65, and all of
      them showed sterility F1 pollen in. These results demonstrate that the F1 pollen
      sterility is controlled by a single gene locus S-b, and the allelic interaction
      of S-bi and S-bj causes the pollen carrying S-bj allele abortive. A total of 187
      RFLP markers and 500 RAPD primers were used to screen the polymorphism between
      T65 and TISL2; only H08-1300 and Y09-1500, two bands amplified by RAPD primer H08
      and Y09 were found to be polymorphic. Purified H08-1300 and Y09-1500 were used as
      probe to hybridize with DNAs from T65 and TISL2, and the results indicated that
      H08-1300 and Y09-1500 appeared to be single copy in the T65 and TISL2 genome,
      then the RAPD marker were successfully converted into RFLP marker. The two
      markers were then used to perform segregation analysis, the results from co
      segregation analysis of the genotypes of these two markers and the phenotypes of
      pollen fertility with F2 population indicated that the S-b was linked to H08-1300
      and Y09-1500, and the genetic distances between each marker and the locus were
      1.3 cM and 6.6 cM, respectively. To determine the chromosomal position of the S-b
      locus, H08-1300 was cloned and its two ends were partially sequenced. The
      homologous comparative analysis of these sequences with published rice sequences
      with BLAST was performed, and 540 bp of left end sequence of H08-1300 showed 86%
      homologous with the sequence of rice PAC clone P0033D06 (Accession No. AC079357),
      and 94% homologies of 101 bp at right end were also observed. Clone P0033D06 had
      been anchored by RFLP markers R3166 that was located on 18.8 cM position of rice
      chromosome 5 by Japan Rice Genome Program, which suggested that the S-b locus was
      mapped on chromosome 5 and tightly linked with R3166. The gene mapping result
      from this study suggests that using the rice genomic sequences published to
      determine the chromosome position of RAPD marker, as well as linked genes, would
      be a useful approach in tagging new genes.

PMID- 12200862
TI  - Mapping quantitative trait loci for plant height in wheat (Triticum aestivum L.)
      using a F2:3 population.
AB  - To detect quantitative trait loci (QTLs) controlling plant height, the plant
      height of 240 F2:3 lines derived from the cross of a dwarf wheat line ND3338 with
      a tall line F390, was assessed in field trials at two locations with three
      replications in 2000 and 2001. Microsatellite markers were used to construct a
      framework linkage map containing 215 loci with 21 linkage groups, and covering
      the whole genome about 3600cM. With the method of interval mapping, seven
      putative QTLs affecting plant height were detected on chromosomes 1B, 4B (two
      regions), 6A (two regions), 6D and 7A, respectively. Phenotypic variations
      explained by each QTL ranged from 5.2% to 50.1%, and in each environment the
      total putative QTLs explained about 64.8%-75% of the total phenotypic variation
      respectively. A major QTL located on chromosome arm 4BS near the locus Xgwm113,
      around the Rht-Blb locus, explained a large part of the phenotypic variation
      (27.8%-36.2% depending on the years or the locations). Except the QTL on
      chromosome 7A, all the other QTLs from ND3338 decreased the plant height,
      variously from 0.94 cm to 9.33 cm. Most of the identified QTLs were consistent in
      all the environments, and should be useful in future marker-assisted-selection
      programs for breeding dwarf and semi-dwarf wheat cultivars.

PMID- 12200864
TI  - [RAPD markers linked to the stripe rust resistance gene Yr5 in the wheat variety
      Triticum spelta album].
AB  - A total of 520 10-mer random primers were used to identify the RAPD markers
      linked to the Yr5 gene between the near-isogenic line Yr5/6 x Avocet S and
      recurrent parent Avocet S. Three polymorphic DNA fragments, S1496(761),
      S1453(880) and S1418(1950), were found linked to the Yr5 gene. In which the
      genetic distance between S1496(761) and Yr5 gene was 2.7 cM. The fragment
      S1496(761) was recovered from the gel and cloned and sequenced. A pair of
      specific PCR primers was designed based on the sequence. The specific primers
      amplified the same fragment about 761bp as the random primer S1496 did. Because
      the primers could amplify another non-specific fragment, the PCR products must be
      analyzed by electrophoresis on polyacrylamide gels.

PMID- 12200863
TI  - [Construction, characterization and screening of a transformation-competent
      artificial chromosome (TAC) library of wheat-Thinopyrum intermedium translocation
      line with resistance to barley yellow dwarf virus].
AB  - A transformation-competent artificial chromosome (TAC) library was constructed
      from the genomic DNA of wheat-Th. intermidium translocation line HW642 that
      harbor the barley yellow dwarf virus (BYDV) resistance gene derived from Th.
      intermidium. The library consists of 2.3 x 10(6) clones with an average insert
      size of 22kb, representing approximately 2.5 haploid genome equivalents and is
      able to give a greater than 95.77% probability of isolating single-copy DNA
      sequences from this library. The library was stored as frozen cultures in 24 96
      well formats, each well containing approximately 1000 different clones. TAC
      clones containing interest gene could be identified by the pooled PCR technique.
      A sequence characterized amplified region (SCAR) marker cosegregated with BYDV
      resistance gene, derived from a simple sequence repeat (SSR) or microsatellite
      marker wms37 of wheat, was applied to screen the TAC library. Twelve clones were
      successfully selected by the pooled PCR method. PCR products were identified by
      hybridizing with the SCAR marker band of Th. intermidium. Out of 12 clones, 10
      positive clones restricted by Hind III were shown to hybridize with genomic DNA
      of Th. intermidium. These results showed evidences that the 10 clones could be
      used as candidate clones for isolation of BYDV resistance and its related genes,
      and the TAC library is a useful resource for isolating genes.

PMID- 12200865
TI  - [Genetic diversity and differentiation of Fagopyrum tataricum and its related
      species in China].
AB  - Genetic diversity and differentiation among 50 populations of total 8 species and
      1 variety of Fagopyrum tataricum and its related species from 27 counties of
      Sichuan and Yunnan provinces, Southwest China were investigated using allozyme
      electrophoresis. Seven enzymesat 12 loci were assessed. The result shows that
      among 8 species and 1 variety, inbreeding coefficient is -0.54(-)-0.80, which
      means hterozogote excess. Higher genetic diversity was found in the wild related
      species of F. tataricum than in F. tataricum. F. dibotrys has the highest Fst
      value, which means that more genetic variations exist among its populations. The
      lowest Fst value shows that less genetic variations exist among population of F.
      gracilipes whic is close to panmictic There is almost no genetic differentiation
      between populations of F. statice. Genetic similarity is 55.3%-65.2% between
      species of F. tataricum and its related species, which is close to the average
      level among species in seed plants. According to the cluster analysis of genetic
      similarity, F. gracillipes is most close to F. tataricum and F. esculentum.
      Jinsha River region is the distributional and original center of F. tataricum and
      its related species.

PMID- 12200866
TI  - [Sequence analysis of Bt insertion flanking fragments in transgenic Bt cotton].
AB  - The copies of outside gene and DNA structure of integration locus are important
      in high expression and avoidance of gene silence. Many research results showed
      that outside genes were inserted into the plant genome with recombinant type, and
      the integration was related to border T-DNA sequence in the course of
      Agrobaterium mediated transformation. SAR structure was also found in the
      integration location of transformants with direct DNA transformation method. The
      pollen-tube pathway transformation, one of direct DNA transformation method, was
      very successfully used in Bt transgenic cotton in China. But until now there has
      been no report about Bt gene integration. The aim of this research was to
      investigate flanking DNA structure in order to explain the mechanism of direct
      transformation method in the future. The structure of flanking DNA fragments of
      Bt integration in four different transgenic Bt cotton varieties including Simian
      3, 161 resistant breeding line, 161 sensitive breeding line and Guokangmian-1 was
      analyzed with TAIL-PCR and nested PCR. The flanking DNA sequences of different
      self-crossed progenies from one plant are the same. In contrary, their DNA
      sequences are diverse for different breeding lines. Upstream flanking fragments
      in some transgenic cotton contained short transformation plasmid sequences,
      downstream flanking fragments in all the transgenic cotton varieties were
      composed of high percentage AT. The percentage of AT in Simian-3 transgenic Bt
      variety was as high as 92%. All the flanking fragments were of multi-copies and
      similar to repetitive sequences. No recognition sites of TOP enzyme were found in
      these fragments.

PMID- 12200867
TI  - [Integration of DNA clones related to important economic traits of Brassica napus
      onto Arabidopsis genetic map].
AB  - Arbidopsis thaliana and Brassica oilcrops are closely related species in
      Brassicae, Cruciferae, and show highly homologous genomes. After a serial
      important agronomic characteristics of Brassica napus being mapped with probes
      from EST clones of Arabidopsis and DNA clones of rapeseed, DNA segment sequencing
      was performed with 25 clones which were found to be closely linked to the CMS
      restore gene, the boron efficiency gene (BE1), the Sclerotinia resistant QTLs and
      the characteristic of interspecific biomass heterosis in rapeseed respectively.
      Highly homologous sequences were found in Arabidopsis genome by searching the
      relative databases. According to the position of homologous sequences on the
      chromosomes of Arabidopsis, the 25 clones were integrated into the genetic map of
      Arabidopsis. Two markers flanking BE1 in B. napus were integrated into a narrow
      region at the short arm of chromosome 1 of Arabidopsis. One of EST clones, pA24,
      from this region was used as a probe to map B. napus and consequently been
      integrated in a position between the two flanking markers of BE1. This event
      increased the confident for one to map the important characteristics of cultured
      Brassica species via reciprocal comparative mapping between Arabidopsis and
      target Brassica crops.

PMID- 12200868
TI  - [Analysis of factors shaping S. pneumoniae codon usage].
AB  - Streptococcus pneumoniae is a Gram-positive bacteria causing community acquired
      pneumonia, bacteremia, meningitis and otitis media. As a human pathogen, S.
      pneumoniae is the most common bacterial cause of acute respiratory infection and
      otitis media and is estimated to result in over 3 million deaths in children
      every year worldwide. S. pneumoniae has played a pivotal role in the fields of
      genetics and microbiology. The complete genome of S. pneumoniae was sequenced and
      published recently. In order to have a further insight into the synonymous codon
      usage evolution and to study S. pneumoniae gene codon usage pattern in highly and
      lowly expressed genes, factors shaping synonymous codon usage pattern of S.
      pneumoniae were analyzed in this paper. Genes larger than of equal to 300bp of
      the complete genome of S. pneumoniae (1709 genes in total) were analyzed. The
      gene expression level (CAI, codon adaption index), RSCU (relative synonymous
      codon usage), Nc (effective codon numbers), A3s, T3s, G3s, C3s (the frequencies
      of the adenine, thymine, guanine and cytosine at the synonymous third position of
      codons, respectively), GC (frequency of guanine + cytosine in gene sequence),
      GC3s (frequency of guanine + cytosine at the synonymous third position of codons)
      values and multivariate statistics were calculated. The results show that there
      is a significant increment of cytosine (C) usage at the synonymous positions in
      highly expressed genes than lowly expressed genes, while lowly expressed genes
      tend to use guanine (G) at synonymous sites. Gene expression has a significant
      correlation with the first axis of correspondence analysis (COA; R = 0.86) and
      significant effects on codon usage by comparing the codon usage patterns of
      highly expressed genes and lowly expressed genes. The G + C content of genes has
      a moderately correlation with gene expression (R = 0.44) and the first axis of
      the COA (R = 0.51), and therefore shapes gene expression and codon usage in S.
      pneumoniae. The dataset is divided into 6 groups by gene length. Then, gene
      expression level, GC3s and Nc values are compared among 6 different gene length
      groups (> = 300 bp, 2000-2999 bp, 1500-1999 bp, 1000-1499 bp, 500-999 bp, < 500
      bp). CAI, GC3s and Nc values show some differences among different gene length
      groups. Protein hydrophobicities do not show significant influence on codon usage
      pattern. In summary, the natural selection on gene expression level and the base
      composition of genes are the major factors affecting codon usage of S.
      pneumoniae. Gene length shapes codon usage of S. pneumoniae in a minor way.

PMID- 12200869
TI  - The Max network: coordinated transcriptional regulation of cell growth and
      proliferation.

PMID- 12200870
TI  - Cellular responses to telomere shortening: cellular senescence as a tumor
      suppressor mechanism.

PMID- 12200871
TI  - The plant plan: multicellular life in the other Kingdom.
AB  - One must conclude, then, that plants and animals may have evolved in quite
      different fashions. There is no doubt that they have independently evolved
      development, and this is demonstrated by the nonhomology of genes serving
      identical developmental functions in prepattern formation. There is nonetheless
      also no doubt that plants and animals have evolved from a common eukaryotic
      ancestor, as indicated by the clear homology of the genes that control the
      chromatin level of gene regulation. There is also little doubt that some
      developmentally important genes of plants, such as the ethylene and red light
      receptors, have derived from an event of horizontal evolutionary transfer
      specific to plants. And it is at least possible to think that the variation on
      which Darwinian evolution acts in plants results in part from phenomena that are
      not seen in animals, namely, the controlled appearance and Mendelian inheritance
      of epigenetically silenced genes. Genomic and genetic analyses of plants thus
      reveal a type of organism with familiar features, but profound differences from
      the more-studied animals. Only by further study of plants and of animals can we
      fully understand the differences between plants and animals, and consequently
      distinguish between those features of developmental pattern formation and
      cellular signaling that are necessary aspects of complex organisms, and those
      that are accidents of evolutionary history.

PMID- 12200872
TI  - Cell cycle control and cancer.

PMID- 12200873
TI  - Recent studies of the ubiquitin system and the N-end rule pathway.

PMID- 12200874
TI  - [Risk factors for Wilms' tumor development in children].
AB  - INTRODUCTION: Wilms' tumor (WT) is the most frequent embryonic renal neoplasia in
      children. OBJECTIVE: This study was carried out to investigate risk factors in
      the development of WT. MATERIAL AND METHODS: A design of cases and controls,
      proactive, of incident cases, with four controls per case. The study population
      of cases were children of two oncologic reference Center of the Mexican Institute
      of Social Security (IMSS) in the Mexican Federal District during 5-year period.
      For the control group, children were frequency matched by age and sex at with
      cases from the same clinic. A questionnaire, previously validated, was applied to
      determine risk factors in both groups. RESULTS: During the period of study, 34
      cases and 136 controls were revised. Significant risk factors were: antecedent of
      a relative with Down syndrome (OR = 7.6, 95%CI 1.4-51.1, p = 0.008), eczema (OR =
      3.7, 95%Cl 1.1-12, p = 0.01); having been conceived in autumn (OR = 5.4, 95%CI
      1.3-31.6, p = 0.007) or winter (OR = 4.9, 95%Cl 1.1-29.9, p = 0.01), and beet
      ingestion (OR = S. 7, 95%Cl 1.7-19.4, p = 0.0007). CONCLUSIONS: In this study,
      influence of prenatal factors are shown and we attempt to explain the etiology of
      WT, the important of beet ingestion, and conclusions suggest that that more
      epidemiologic studies are necessary to determine the chain of events that causes
      Wilms' tumor.

PMID- 12200875
TI  - [Renal trauma in childhood. Second-level hospital experience].
AB  - The leading cause of death in children is accidents. Severe craniocerebral trauma
      and injuries to the heart or major vessels are mainly responsible for immediate
      death. This phenomenon is also reflected in the increasing number of pediatric
      admissions for renal trauma. MATERIAL AND METHODS: From 1990 to 2000, the charts
      of 132 patients with renal injuries secondary to blunt and penetrating trauma in
      childhood are reviewed. RESULTS: A total of 88 were male patients and 126
      sustained blunt trauma (motor accidents, falls, etc.). Gross and microscopic
      hematuria were the most important finding at the time of presentation, and
      correlated with severe renal injury, and both were present in 122 cases.
      Intravenous pyelography and CT scan were the most useful diagnosis tools. Only 27
      patients were managed operatively, the majority because of associated intra
      abdominal injury. CONCLUSIONS: Intravenous pyelography remains the most cost
      effective means of investigating renal injuries in a second-level hospital. Renal
      contusion and most laceration should be managed conservatively. Only few a renal
      transactions should be managed operatively.

PMID- 12200876
TI  - [White-coat hypertension and risk factors in recently diagnosed hypertensive
      patients].
AB  - OBJECTIVE: To determine the frequency of white-coat hypertension (WCH) and
      associated risk factors in recently diagnosed hypertensive patients. MATERIAL AND
      METHODS: A cross-sectional study was carried out from January 1997 to December
      1998. The reference population consisted of 195 patients presenting with systemic
      arterial hypertension (SAH) of less than 1-month evolution and receiving no
      medical treatment. According to Joint National Committee (JNCVI) criteria, 100
      individuals with Stages I, II, and III SAH underwent the following procedures:
      clinical history; physical examination; electrocardiogram, serum creatinine;
      urianalysis, and ambulatory monitoring of arterial pressure (AMAP). RESULTS: A
      total of 54% of patients were WCH carriers and 46% presented sustained
      hypertension (SH); 37% of WCH patients and 63% of SH patients had a family
      history of SAH, while 19.7% of WCH patients and 39.2% of SH patients presented
      with stage 1 retinopathy. Left ventricular hypertrophy was absent in all WCH
      patients and present in 21.7% of SH patients. A total of 31% of WCH patients and
      50% of SH patients presented electrocardiographic changes. CONCLUSIONS: A total
      of 54% of patients presented WCH. Clinical/epidemiologic profiles of WCH carriers
      and SH patients are different.

PMID- 12200877
TI  - [Survival in patients with liver cirrhosis at the Durango, IMSS Regional General
      Hospital].
AB  - INTRODUCTION: In Mexico, hepatic cirrhosis mortality exhibits important regional
      differences. AIM: To analyze global survival of cirrhotic patients, according to
      etiology and functional status. MATERIAL AND METHODS: Between March 1990 to
      August 1998, newly diagnosed patients with hepatic cirrhosis were included in a
      follow-up study. Subjects were analyzed monthly. Information on clinical
      evolution, complications, and dates of events (death) and complications were
      registered. Survival was estimated using Kaplan-Meier method. RESULTS: Ninety
      nine subjects were included in the survival analysis, 66 with alcoholic and 33
      with viral cirrhosis (HCV and HBV in 24 and nine patients, respectively). Ninety
      seven percent of patients were decompensated at diagnosis, and 81% had ascites.
      Probabilities for survival in the entire series were 69.7, 37.6 and 23.6% at 24,
      48, and 60 months, respectively. There were no significant differences in the
      survival of patients grouped according to etiology. When survival was analyzed by
      Child-Pugh score, it was slightly higher in the alcoholic cirrhosis group.
      CONCLUSIONS: In this study survival probability of patients with viral cirrhosis
      was lower than in patients with alcohol cirrhosis.

PMID- 12200878
TI  - [Factors that modified medical practice].

PMID- 12200880
TI  - [Cesarean-associated complications: the importance of a scarcely justified use].
AB  - Undoubtedly, cesarean section is one of the most important surgical procedures
      for solving obstetrical problems. However, the steady increase in its use might
      be reflecting a non-medically justified utilization. This work reviews the main
      complications associated to cesarean section and their effect on the health of
      mothers and their children. An additional objective is to highlight the
      importance of establishing clinical protocols aimed at identifying those cases in
      which a cesarean section should be practiced. The implementation of these
      guidelines might help to reduce the effect that factors such as preferences of
      medical personnel or women's demand exert upon the increase of cesarean section
      use.

PMID- 12200879
TI  - [Medical methods for pregnancy termination. A review of literature and its
      potential role in Mexico and Latin America].
AB  - In this document, we review the relevant aspects of the different medical methods
      of abortion. We describe the principal medical regimens currently used in North
      America, Europe, and a growing number of developing countries. We also describe
      specific treatment regimens (which usually involve a combination of two drugs),
      physiological methods of action, potential side effects and complications, method
      requirements, including follow-up visits, any existing contraindication, and
      acceptability of these methods among patients. Finally, we comment on the
      potential role of medical abortion in Mexico and throughout Latin America.

PMID- 12200881
TI  - [A 66-year-old female with enlarged and firm left axillary lymph node].

PMID- 12200882
TI  - [George H. Whipple. Nobel Prize in Physiology or Medicine in 1934. Whipple's
      disease, pernicious anemia, and other contributions to medicine].
AB  - George Hoyot Whipple (1878-1976) was awarded the Nobel Prize in Physiology and
      Medicine in 1934, along with Minot and Murphy for their studies in pernicious
      anemia. Whipple's name has been given to the bacterial disease which he describes
      in 1907 that we know today as Whipple's disease or intestinal lipodystrophy. He
      gave the name of thalasemia to the Mediterranean anemia of Cooley, and made
      diverse contributions to hematology and general pathology. He worked with William
      Welch in the Department of Pathology at Johns Hopkins Hospital and later became
      director of the University of Rochester. He died in 1976 at the age of 98.

PMID- 12200883
TI  - [Multiple vertebral hemangiomas].

PMID- 12200884
TI  - [New treatments for spinal cord injuries].

PMID- 12200886
TI  - [Human reproductive cloning].

PMID- 12200885
TI  - [Alterations in hepatitic metabolism induced by prolonged-action nifedipine in
      Mexican population].

PMID- 12200887
TI  - [Dr. Ignacio Chavez conference. About the vanishing art of curing].

PMID- 12200888
TI  - [Similarities].

PMID- 12200889
TI  - ORACLE--antibiotics for preterm prelabour rupture of the membranes: short-term
      and long-term outcomes.
AB  - Preterm prelabour rupture of the foetal membranes (pPROM) is the most common
      antecedent of preterm birth and can lead to death, neonatal disease and long-term
      disability. Previous small trials of antibiotics for pPROM suggested some health
      benefits for the neonate, but the results were inconclusive. A large, randomized,
      multicentre trial was undertaken to try to resolve this issue. In total, 4826
      women with pPROM were randomized to one of four treatments: 325 mg co-amoxiclav
      plus 250 mg erythromycin, co-amoxiclav plus erythromycin placebo, erythromycin
      plus co-amoxiclav placebo, or co-amoxiclav placebo plus erythromycin placebo,
      four times daily for 10 d or until delivery. The primary outcome measure was a
      composite of neonatal death, chronic lung disease or major cerebral abnormality
      on ultrasonography before discharge from hospital. The analysis was undertaken by
      intention to treat. Indications of short-term respiratory function, chronic lung
      disease and major neonatal cerebral abnormality were reduced with the
      prescription of erythromycin. In contrast, the use of co-amoxiclav was associated
      with a significant increase in the occurrence of neonatal necrotizing
      enterocolitis. CONCLUSION: Prophylactic antibiotics can play a role in preterm
      prelabour rupture of the membranes in reducing infant morbidity.

PMID- 12200890
TI  - Prophylactic high-frequency oscillatory ventilation in preterm infants.
AB  - The role of high-frequency oscillatory ventilation (HFOV) for the treatment of
      respiratory disease in preterm infants remains uncertain. Several randomized
      trials, comparing HFOV and conventional ventilation (CV) have been performed and
      their results suggest that HFOV may reduce the incidence of chronic lung disease
      (CLD) in preterm infants. However, the trials have several limitations and it
      remains unclear whether HFOV might increase intracranial pathology in very
      prematurely born infants. UKOS, a large, UK-based, multicentre trial was
      conducted to establish conclusively the role of prophylactic HFOV for the
      prevention of CLD in infants born prior to 29 wk of gestational age. CONCLUSION:
      There is still a need to fully evaluate prophylactic HFOV with particular
      emphasis on both short and long term respiratory and neurological outcomes.

PMID- 12200891
TI  - Respiratory mechanical unloading and proportional assist ventilation in infants.
AB  - Conventional patient-triggered ventilation attempts to synchronize the upstroke
      in ventilator pressure with the onset of spontaneous inspiration. Other
      parameters of the mechanical cycle such as the peak inspiratory pressure are
      preset by the clinician. They will be imposed on the infant regardless of the
      actual spontaneous respiratory drive. Proportional assist ventilation (PAV) and
      respiratory mechanical unloading of spontaneous breathing (RMU, resistive and
      elastic unloading) are based on fundamentally different concepts. In contrast to
      the conventional perception of the ventilator being a pump, RMU/PAV servo
      controls the applied ventilator pressure continuously throughout each
      inspiration. These modalities proportionally enhance the effect on ventilation of
      each respiratory effort. They rely on rather than interfere with the subject's
      respiratory control system. The patient controls all variables of the respiratory
      pattern while the ventilator works fully enslaved as a proportional amplifier.
      Back-up conventional mechanical ventilation is initiated during episodes of
      hypoventilation and apnoea. The clinician sets the degree of the assist during
      RMU/PAV in terms of "gains". Selecting specific gains for the elastic and
      resistive unloading components allows the ventilator pressure waveform to be
      tailored to the individual degree of restrictive and obstructive pulmonary
      disease. This results in a reduction in the transpulmonary pressure cost of
      ventilation compared with conventional modes. CONCLUSION: Further studies on
      RMU/PAV are required to evaluate clinically important long-term outcome variables
      in infants and to determine whether the benefits outweigh potential drawbacks and
      the complexity involved in these new modes of mechanical ventilation.

PMID- 12200892
TI  - Role of platelet-activating factor in the pathophysiology of necrotizing
      enterocolitis.
AB  - Necrotizing enterocolitis (NEC) is a devastating gastrointestinal illness that
      affects predominantly preterm infants. Treatment options are limited and NEC
      remains a significant cause of morbidity and mortality. The precise aetiology of
      NEC remains unclear but evidence strongly suggests that the cause is
      multifactorial and there are four main aetiological factors: prematurity,
      hypoxia, enteral feeding and bacterial colonization. The presence of similar
      intestinal lesions, regardless of aetiological trigger, strongly implicates a
      final common pathway in the pathogenesis. There is now a substantial body of
      evidence to indicate that endogenous inflammatory mediators, particularly
      platelet-activating factor (PAF), play a vital role in this final pathway.
      CONCLUSION: The use of agents that antagonize PAF may provide therapeutic options
      in the management of NEC.

PMID- 12200894
TI  - Pathogenesis of retinopathy of prematurity.
AB  - Retinopathy of prematurity (ROP) is a blinding disease, initiated by delayed
      retinal vascular growth after premature birth. There are both oxygen-regulated
      and non-oxygen-regulated factors, which contribute to both normal vascular
      development and retinal neovascularization. One important oxygen-regulated
      factor, critical to both phases of ROP, is vascular endothelial growth factor
      (VEGF). A critical non oxygen-regulated growth factor is insulin-like growth
      factor (IGF-1). In knockout mice, lack of IGF-1 prevents normal retinal vascular
      growth, despite the presence of VEGF, important to vessel development. In vitro,
      low IGF-1 prevents vascular endothelial growth factor-induced activation of Akt,
      a kinase critical for vascular endothelial cell survival. Premature infants who
      develop ROP have lower levels of serum IGF-1 than age-matched infants without
      disease. CONCLUSION: IGF-1 is critical to normal vascular development. Low IGF-1
      predicts ROP and restoration of IGF-1 to normal levels may prevent ROP.

PMID- 12200893
TI  - Role of oxidant injury in the pathogenesis of neonatal lung disease.
AB  - Bronchopulmonary dysplasia (BPD) is a chronic lung disease that develops in
      newborn infants treated with oxygen and mechanical ventilation for a primary lung
      disorder. With significant improvements in survival of many critically ill
      infants, BPD has become an extremely important complication of newborn intensive
      care. The pathogenesis of BPD is complex and involves a variety of causative
      factors. However, increasing evidence has suggested that an oxidative insult
      could be an extremely important component of the injury process. Premature
      infants are especially sensitive to oxidant injury since they are exposed to
      supraphysiological concentrations of oxygen at birth while endogenous antioxidant
      enzyme activity may be relatively deficient. CONCLUSION: Superoxide dismutase is
      an antioxidant enzyme that has been shown in numerous basic and clinical studies
      to protect cells against oxidant injury.

PMID- 12200895
TI  - Origins of reactive airways disease in early life: do viral infections play a
      role?
AB  - There is mounting evidence suggesting that infection with respiratory syncytial
      virus (RSV) in early life increases the risk of developing reactive airway
      disease (RAD) later in childhood. A recent prospective study demonstrated that
      children hospitalized with RSV bronchiolitis in infancy face a significantly
      increased risk of recurrent wheezing and allergy at least until the age of 7 y
      that is independent of hereditary factors. Proposed mechanisms for this link
      include immune dysregulation, in which RSV-specific IgE or an imbalance between T
      lymphocyte-dependent immune pathways may be involved, and abnormal neural
      control, in which the non-adrenergic, non-cholinergic pathways are altered by RSV
      infection. More recent studies suggest that immune and neural mechanisms may be
      linked and that post-RSV airway inflammation may be explained, at least in part,
      on the basis of these neuroimmune interactions. CONCLUSION: Passive
      immunoprophylaxis may protect against persistent viral-induced inflammation of
      the respiratory tract, long-term changes in pulmonary function and increased
      frequency of RAD episodes.

PMID- 12200896
TI  - Pain management in French neonatal intensive care units.

PMID- 12200897
TI  - Thrifty genotypes and phenotypes in the pathogenesis of early-onset obesity.

PMID- 12200898
TI  - Swedish population-based longitudinal reference values from birth to 18 years of
      age for height, weight and head circumference.
AB  - This study aimed to update growth reference values for height, weight and head
      circumference in order to reflect the changes in body size in the Swedish
      population during the past two decades. The data came from a large longitudinal
      growth study on 3650 full-term healthy Swedish children who were born between
      1973 and 1975. All of these 1801 girls and 1849 boys had longitudinal data for
      height and weight from birth to final height. Comparison with previous Swedish
      growth reference values based on children born between 1955 and 1958 revealed
      that there have been secular changes in body size. For instance, at 18 y of age,
      the updated height and weight reference values are 180.4 cm for males and 167.7
      cm for females, i.e. 1.9 cm taller and 5.7 kg heavier for males and 2.3 cm taller
      and 3.4 kg heavier for females compared with the previous reference values.
      CONCLUSION: These new growth reference values provide current national standards
      for growth monitoring and evaluation since the year 2000.

PMID- 12200899
TI  - Body composition, as assessed by bioelectrical impedance spectroscopy and dual
      energy X-ray absorptiometry, in a healthy paediatric population.
AB  - The aim of this study was to determine the level of agreement between body
      composition measurements by dual-energy X-ray absorptiometry (DXA), single
      frequency bioelectrical impedance analysis (BIA) and multifrequency bioelectrical
      impedance spectroscopy (BIS). Fat-free mass (FFM), body fat mass and body fatness
      (percentage fat) were measured by DXA, BIA and BIS in 61 healthy children (37M,
      24F, aged 10.9-13.9 y). Estimates of FFM, body fat mass and body fatness were
      highly correlated (r = 0.73-0.96, p < 0.0001) between the different methods.
      However, a Bland-Altman comparison showed wide limits of agreement between the
      methods. The mean differences between methods for FFM ranged from -2.31 +/- 7.76
      kg to 0.48 +/- 7.58 kg. Mean differences for body fat mass ranged from 0.16 +/-
      5.06 kg to 2.95 +/- 5.65 kg and for body fatness from -2.3 +/- 7.8% to 0.8 +/-
      9.3%. Calculations of body composition with BIS were not superior to BIA.
      However, BIA overestimated fat mass in lean, subjects and underestimated fat mass
      in overweight subjects more than BIS, compared with DXA. CONCLUSION: The methods
      used provided estimates of FFM, body fat mass and body fatness that were highly
      correlated in a population of healthy children. However, the large limits of
      agreement derived from the Bland-Altman procedure suggest that the methods should
      not be used interchangeably.

PMID- 12200900
TI  - Calcium, iron and zinc availability from weaning meals.
AB  - During the weaning period, solid foods are introduced in the diet to complement
      human milk or infant formula. Consequently, marginal deficiencies may easily
      develop because of inappropriate feeding and low bioavailability of nutrients.
      The objective of this study was to determine calcium, iron and zinc availability
      from weaning foods that contained a variety of ingredients but almost the same
      dietary fibre content, and to describe dietary factors that influence
      availability in a linear matter. Availability measurements from eight meals were
      made in vitro by a continuous-flow dialysis system with preliminary intraluminal
      digestion. Calcium, iron and zinc were analysed by flame atomic absorption
      spectrometry; ascorbic acid content was taken from food-composition tables; and
      macronutrient and mineral contents were obtained from the manufacturer. Calcium
      availability was higher in fruits (mean +/- SD, 39.2 +/- 4.1%) than vegetables
      (31.7 +/- 5.8%) (p < or = 0.001). Iron availability was marginally significant
      higher in vegetables (13.0 +/- 4.7%) than fruits (10.2 +/- 1.6%) (p = 0.027).
      Zinc availability showed higher availability in fruits (52.3 +/- 22.3%) than
      vegetables (22.1 +/- 5.6%) (p < or = 0.001). CONCLUSION: A major portion (47.8%)
      of the variance in calcium availability, as determined by multiple regression,
      could be explained by protein (p = 0.058, beta = -0.691). Major predictors of
      iron availability among the nutrients were iron content of the meal (p = 0.014,
      beta = -0.838), carbohydrates (p = 0.044, beta = -0.610) and dietary fibre (p =
      0.235, beta = -0.285). Zinc availability was merely influenced by the protein (p
      = 0.010, beta = -0.876) and fat content of the meals (p = 0.295, beta = 0.255) in
      relation to other nutrients.

PMID- 12200901
TI  - Prospective population-based study on rotavirus disease in Germany.
AB  - The aim of this study was to collect representative data on the incidence and
      clinical characteristics of community-acquired acute gastroenteritis (AGE) due to
      rotavirus (RV) in German children up to 4 y of age. In 20 paediatric practices in
      5 German regions every child aged 0-4 y presenting with symptoms of AGE from May
      1997 to April 1998 was eligible for inclusion into the study. Stool samples were
      tested for RV antigen by enzyme-linked immunosorbent assay and polymerase chain
      reaction was performed for serotyping. The course of the disease, additional
      diagnoses and treatment regimen were recorded. Incidences adjusted for month and
      region of observation were calculated by Poisson regression. Of 15,451 children
      under observation 3980 (26%) presented with AGE. Of 3156 stool samples available
      748 (24%) proved RV positive. The incidence of AGE and RV-positive AGE was 25.2
      and 4.0 per 100 children per year, respectively, with a maximum in February/March
      1998. RV-positive cases were more severe than RV-negative cases (28% vs 12%
      severe cases, hospitalization rate 6.2% vs 2.0%, p < 0.001). The predominant
      genotype of RV isolated was G1/P[8] (77%), followed by G4/P[8] (17%). CONCLUSION:
      Rotavirus accounts for a substantial part of severe cases of AGE in children up
      to 4 y of age. Efficient prevention, including immunization against the
      circulating serotypes, could save at least 122,000 children in Germany from
      falling ill with RV-AGE each year.

PMID- 12200902
TI  - Dynamics of progression markers in a non-study population of human
      immunodeficiency virus-1 vertically infected infants with different
      antiretroviral treatments.
AB  - Treatment with highly active antiretroviral therapy (HAART) has been shown to
      modify viral replication dynamics and lead to a significant recovery of CD4+ T
      cells. A retrospective multicentre observational study was performed in a non
      study population of 151 HIV-1-infected children, categorized into four groups
      according to therapy: untreated (NT), on monotherapy (MT) with a nucleoside
      inhibitor, on combination therapy (CT) with two nucleoside inhibitors, and on
      HAART, protease inhibitor containing regimens, to assess the "real-life"
      effectiveness of these different therapies on plasma viral load (VL) and CD4+ T
      cells. VL was quantified using a standard molecular assay. CD4+ and CD8+ T-cells
      subsets were determined by flow cytometry. The HAART group showed the highest
      relative proportion (RP) of increases in 5, 10, 15 and 20% of CD4+ T-cells over
      baseline, and the earliest fall-off of VL (0.5, 1, 1.5 and 2 log10 copies ml-1).
      The RP of the fall-off of 0.5, 1, 1.5 and 2 log10 VL below baseline was 3-fold
      higher in HAART group than in the MT and CT groups. However, no differences were
      found among the groups of treated children in reaching undetectable VL.
      CONCLUSION: A better evolution of VL and CD4+ T-cells was evident in children on
      HAART, indicating a positive effect on the immune system and clinical status,
      inhibiting HIV-1 replication and enabling the recovery of CD4+ T-cell counts.

PMID- 12200903
TI  - Characteristic profile of intestinal microflora in Kawasaki disease.
AB  - To investigate whether the ecology of the intestinal microflora may change in the
      acute phase of Kawasaki disease (KD), the distribution pattern was studied of
      common micro-organisms in feces from 20 patients with KD, 20 patients with acute
      febrile diseases (disease control) and 20 healthy children. KD patients had a
      significantly lower (p < 0.001) incidence of Lactobacillus (2/20, 10%) than
      disease control patients (16/20, 80%) and healthy children (14/20, 70%). KD
      patients had no significant incidences of other microbial genera, compared with
      both disease control and healthy children. CONCLUSION: The results suggest that a
      lack or loss of the beneficial Lactobacillus genus in the enteric microflora may
      occur during the acute phase of KD.

PMID- 12200904
TI  - Lung function and asthma symptoms in children: relationships and response to
      treatment.
AB  - The aim of this study was to determine the relationships between the forced
      expiratory volume in 1 s (FEV1), peak expiratory flow (PEF) and asthma symptom
      scores, as well as their response to treatment, in children with no recent
      exacerbations of asthma. Asthma symptom scores, FEV1 and PEF were characterised,
      and their relationships and changes at follow-up studied in 64 children (mean age
      9.5 y) referred to asthma outpatients. The mean FEV1 and PEF at the initial
      clinic visit were 94% of predicted values. At follow-up, mean FEV1 and PEF were
      similar. However, symptom scores (maximum obtainable score for each variable = 3)
      for exercise, nocturnal cough and morning cough were abnormal at the initial
      visit (mean +/- SD, exercise 1.0 +/- 0.7, nocturnal cough 1.7 +/- 1.2, morning
      cough 1.6 +/- 1.2) and improved significantly at follow-up (exercise 0.8 +/- 0.7,
      nocturnal cough 0.9 +/- 1.1, morning cough 1.0 +/- 1.2) (p < 0.05). A significant
      relationship was not observed between lung function and total symptom score, at
      either the initial or follow-up clinic visit. Neither FEV1 nor PEF significantly
      correlated with individual symptom scores. While symptom control improved, no
      significant relationships between change in asthma symptom scores and change in
      FEV1 and PEF between the initial and follow-up visits were observed. CONCLUSION:
      Clinic ("office") spirometry, currently performed world-wide, cannot be uniformly
      regarded as an indicator of asthma status. In addition to the measurement of lung
      function, quantitative symptom scoring may be a helpful tool for physicians in
      the assessment of childhood asthma status.

PMID- 12200905
TI  - Antioxidant effect of beta-carotene in cystic fibrosis and bronchiectasis:
      clinical and laboratory parameters of a pilot study.
AB  - The carotenoids are potent antioxidants with the ability to quench singlet oxygen
      and other toxic oxygen species. The aim of this pilot study was to investigate
      the protective effect of beta-carotene on oxidant system in patients with cystic
      fibrosis (CF) and in patients with bronchiectasis (BE) caused by a reason other
      than CF. Eighteen children with CF and 15 children with BE followed in the
      Pediatric Chest Disease Unit of Hacettepe University, and 15 healthy children
      participated in the study. Compared with the controls, significantly lower plasma
      levels of beta-carotene were found in the CF group and significantly lower plasma
      levels of vitamin E in the CF and BE groups. The standardization of carotenoid
      levels for total cholesterol did not significantly attenuate these differences.
      In addition, there were significantly higher levels of malondialdehyde (a marker
      of lipid peroxidation) and tumour necrosis factor-alpha (TNF-alpha) in children
      with CF and in children with BE than in normal subjects. After 6 mo of beta
      carotene supplementation, the plasma levels of beta-carotene and vitamin E
      increased and the plasma levels of TNF-alpha and malondialdehyde decreased in
      both groups. CONCLUSION: Potent antioxidants, beta-carotene and vitamin E are
      deficient in patients with CF and in patients with BE, and they are more
      susceptible to oxidative damage. These patients may benefit from beta-carotene
      supplementation.

PMID- 12200906
TI  - Cardiovascular changes in children with mucopolysaccharide disorders.
AB  - The aims of this study were to evaluate cardiac involvement, assess risk factors
      and mortality, and define the outcome of cardiac abnormalities with age in the
      different types of mucopolysaccharidoses (MPS). The echocardiograms of 99
      patients with MPS, aged 1-24 y (median age 10.3 y) were reviewed between 1978 and
      2000. Mitral regurgitation (MR) was detected in 29 patients (29%). MR was more
      frequent in types IH [n = 11 (38%)], II [n = 10 (24%)] and III [n = 4 (20%)].
      Sixteen patients (16%) developed aortic regurgitation (AR), seen mostly in types
      II [n = 9 (56%)] and IV [n = 4 (24%)]. AR and/or MR was detected in 37 patients
      and 8 had both abnormalities of borderline significance (odds ratio 2.95, 95%
      confidence interval 1.0-8.85, p = 0.05). Of 99 patients, 47 had a normal study on
      their first echocardiogram, whereas only 7 had a normal study on subsequent
      echocardiograms. Fifty-four (54%) had a single echocardiogram. Of these, 27 (50%)
      were abnormal and 27 normal. Forty-five patients had more than one
      echocardiogram, of which 25 (56%) were abnormal and 20 normal. In 13/20 (65%) a
      cardiac abnormality developed on a subsequent echocardiogram which was
      statistically significant (p = 0.002). Overall mitral and aortic valve
      abnormalities showed a positive association with age. Univariate analysis of risk
      factors showed that increasing age, MPS I and ejection fraction were significant
      risk factors for death. However, left ventricular hypertrophy, mitral valve
      abnormalities and type II MPS were not significant risk factors for death, with
      borderline significance for aortic valve abnormalities. CONCLUSION: This study
      demonstrates the evaluation of ventricular function, which is a significant risk
      factor for death, along with increasing age and MPS I, and outlines the
      borderline significance of aortic valve abnormalities, which has not been
      mentioned in previous studies. It also shows that mitral valve lesions, commonly
      seen in MPS, were not a significant risk factor for death. The results emphasize
      the importance of performing serial echocardiograms in patients with MPS to
      assess ventricular function and the progression of cardiac abnormalities with
      age.

PMID- 12200907
TI  - Phenylalanine hydroxylase mutations and phenylalanine-tyrosine metabolism in
      heterozygotes for phenylalanine hydroxylase deficiency.
AB  - The aim of this study was to determine whether any relationship exists between
      the severity of mutation of the phenylalanine hydroxylase (PAH) gene and the
      plasma concentrations of phenylalanine (Phe) and tyrosine (Tyr) under fasting and
      semifasting conditions among heterozygotes in a matched case-control study.
      Parents of patients affected by PAH deficiency (n = 25) detected through the
      Italian Neonatal Screening Program and referred from January 1994 to June 2000,
      and parents of healthy children were investigated. In total, 68 subjects without
      any disease, 34 hyperphenylalaninaemia (HPA) heterozygous parents and 34 age- and
      gender-matched controls, were recruited. Plasma concentrations of Phe and Tyr in
      fasting and semifasting (1600 mg Phe oral load) conditions were the main outcome
      measures. DNA analysis for PAH mutations was performed in all 68 subjects.
      Compared with controls, heterozygotes showed higher fasting and semifasting Phe
      concentrations (p < 0.0001), lower semifasting Tyr concentrations (p = 0.015),
      lower Tyr variations (p = 0.003) and a higher Phe/Tyr ratio (p < 0.0001) in
      switching from fasting to semifasting conditions. Heterozygotes carrying a severe
      mutation showed semifasting plasma Tyr concentrations lower than controls (p =
      0.019) but not significantly different from Tyr levels found in non-severe
      carriers (p = 0.197). The Tyr variations were minor in severe carriers than
      controls (p < 0.001) and non-severe carriers too, although with lower
      significance (p = 0.089). In six carriers of A403V mutation, parents of mild
      hyperphenylalaninaemics on an unrestricted diet, significant differences in
      variations from fasting to semifasting conditions were found compared with
      parents of patients on a diet. CONCLUSION: Although the great heterogeneity of
      PAH mutations limits any general conclusion, the results suggest that monitoring
      plasma Tyr variations may be more sensitive than plasma Phe in assessing the
      severity of PAH mutations in HPA heterozygotes.

PMID- 12200908
TI  - Perinatal water intoxication due to excessive oral intake during labour.
AB  - The increased body water in pregnant women and the birth-related activation of
      water-sparing systems contribute to a high risk of perinatal water intoxication
      if the mother drinks too much water during labour. This study reports on four
      newborn term infants and one mother presenting with life-threatening symptoms due
      to hyponatraemia from excessive oral intake during labour. Awareness of this
      diagnosis in the delivery unit is very important, because the clinical picture
      may mimic that of pre-eclampsia or dehydration. CONCLUSION: Guidelines are
      proposed to prevent and treat perinatal water intoxication due to excessive oral
      intake during labour.

PMID- 12200909
TI  - Body composition in infants with chronic lung disease after treatment with
      dexamethasone.
AB  - The aim of this study was to study the effect of chronic lung disease (CLD) and
      dexamethasone treatment on body composition in preterm infants (birthweight <
      1500 g). In addition, anthropometric measurement of body composition were
      compared with dual-energy X-ray absorptiometry (DXA). Fourteen preterm infants
      with CLD and a comparison group of 18 preterm infants were studied until 3 mo
      corrected age. CLD infants received approximately 20 kcal kg-1 per day extra
      nutritional intake during dexamethasone treatment until term. At term no
      differences were found between CLD and no CLD infants for percentage bone mass
      (1.4 +/- 0.2 vs 1.4 +/- 0.1%), fat mass (18.7 +/- 4.5 vs 17.4 +/- 3.5%), lean
      body mass (79.9 +/- 4.6 vs 81.2 +/- 3.5%) or bone mineral density (0.15 +/- 0.02
      vs 0.15 +/- 0.01%). At 3 mo corrected age both groups were also similar for bone
      mass (1.6 +/- 0.1 vs 1.6 +/- 0.2%), fat mass (22.6 +/- 5.5 vs 24.5 +/- 5.7%),
      lean body mass (75.8 +/- 5.7 vs 74.0 +/- 5.8%) and bone mineral density (0.20 +/-
      0.02 vs 0.20 +/- 0.01%). All anthropometric measurements showed a high
      correlation with body composition. However, calculated fat mass was 56.7 +/- 8.8%
      lower than fat mass measured with DXA. CONCLUSION: Body composition at term and 3
      mo corrected age in preterm infants treated with dexamethasone for CLD, who
      received extra caloric intake until term, did not differ from that in preterm
      infants without CLD.

PMID- 12200910
TI  - Pain management in French neonatal intensive care units.
AB  - The aim of this study was to investigate pain management in neonatal intensive
      care units (NICUs) in France and to identify factors associated with variability
      across units. A questionnaire sent to 143 heads of level II or III NICUs
      investigated the use of pain scores, pain management organization and
      pharmacological treatment in five clinical situations (endotracheal intubation,
      prolonged mechanical ventilation, acute stage of necrotizing enterocolitis,
      central venous catheter insertion and cephalhaematoma). The response rate was
      81%. Among the 35 (30%) units that used no pain scores, 40% ascribed this to lack
      of knowledge. Factors associated with failure to use pain scores were level II
      status, no university affiliation, no surgical patients and neonatal patients
      only. Among the units that scored pain, 78% used valid scores for acute pain and
      73% for prolonged pain. Written guidelines were available for acute pain in 65%
      of units and for prolonged pain in 36%. The rate of pharmacotherapy use varied
      widely across the five clinical situations studied (from 16 to 77%) and across
      units for a given clinical situation. Also extremely variable were the regimens
      used in each situation and the dosages of analgesics and sedatives. Only 11% of
      units adjusted dosages to gestational age. CONCLUSION: Pain assessment was
      performed in the most French NICUs, but a strong heterogeneity for pain treatment
      was observed. Reference to recently published pain management guidelines and new
      randomized trials could be useful to optimize pain treatment in NICUs.

PMID- 12200911
TI  - Overweight among international adoptees in Sweden: a population-based study.
AB  - This study investigated the prevalence of overweight [body mass index (BMI) > or
      = 25 kg m-2] in young adulthood among international adoptees. The prevalence of
      overweight among adoptees from various countries of origin was compared with that
      in a large group of non-adopted individuals. All 275,026 young men born in 1973
      1977 and living in Sweden at 17 y of age were included. A record linkage was made
      between the Military Service Conscription Register and several population
      registers. Data on BMI at 18 y of age were obtained from military conscription
      examinations conducted in 1991-1995. BMI was missing for 12.7% of 2400 adoptees
      and 10.8% of 263,173 non-adoptees. Among 623 adoptees from Latin America 21.5%
      (95% confidence interval 18.3-24.7) were overweight, with a particularly high
      prevalence of overweight among the 266 adoptees from Chile (28.6%, 23.1-34.0).
      Among 502 adoptees from the Indian subcontinent 8.4% (5.9-10.8) were overweight
      and the prevalence of overweight was 8.8% (5.7-12.0) among 317 adoptees from
      India. Among 817 adoptees from the Far East 12.0% (9.8-14.2) were overweight and
      the prevalence of overweight was 10.9% (7.9-13.9) among 404 from South Korea. The
      corresponding figure was 14.1% (14.0-14.2) among the non-adopted individuals.
      CONCLUSION: These differences in prevalence of overweight between various groups
      of adoptees and between adopted and non-adopted subjects are remarkable and are
      probably due to diversity in genetic susceptibility to overweight.

PMID- 12200912
TI  - Prevalence and associated impairments of mild mental retardation in six- to ten
      year old children in Pakistan: a prospective study.
AB  - The aim of this study was to find the prevalence of mild mental retardation (MMR)
      in 6-10-y-old children in a prospectively followed cohort in Pakistan from four
      areas with different socioeconomic conditions. Retarded children were identified
      by a two-step method, comprising a household screening with the Ten Questions
      Screening in 649 families followed by clinical investigation and psychometric
      testing (WISC-R and Griffiths) of the 132 children found by the screening. The
      overall prevalence of MMR among 6-10-y-old children was 6.2%. The distribution of
      MMR was uneven, with 1.2% among children from the upper-middle class, 4.8% in the
      village, 6.1% in the urban slum and 10.5% in the poor periurban slum area.
      Additional impairments were found in 75% of the children with MMR, of which
      speech impairment was the most common. CONCLUSION: The prevalence of MMR was
      found to be higher in a developing country than in developed countries. It also
      seemed to be related to poor socioeconomic conditions, as the prevalence in the
      upper-middle class was comparable to figures from developed countries, while the
      prevalence in children from poor population groups was much higher.

PMID- 12200913
TI  - Health, health-compromising behaviour, sexuality and involvement in pregnancy
      among 18-year-old Swedish males: a cross-sectional survey.
AB  - The aim of this study was to determine whether there are differences regarding
      well-being, health habits and health-compromising behaviour between Swedish young
      men who had never had sexual intercourse (group I), those who were sexually
      active but without a pregnancy record (group II), and those who had caused
      pregnancies (group III). A self-report questionnaire was used covering questions
      regarding health, health habits and risk behaviour. Tests of significance for
      differences between the three groups were performed with chi 2-tests. Differences
      were found in health, health behaviour and risk-taking behaviour between the
      three groups of young men, with an apparent tendency towards riskier lifestyles
      from group I, through group II, to group III. Two especially striking findings
      were the more frequent use of anabolic steroids and the reported high rate of
      sexual offences in group III compared with groups I and II. CONCLUSION: This
      study highlights serious health-compromising behaviours in 18-y-old men involved
      in pregnancies in a medium-sized Swedish city. This group has been largely
      ignored both in clinical practice and in scientific studies, in contrast to the
      huge efforts directed towards pregnant adolescent females. Public health workers,
      school health programmes and adolescent clinics need to acknowledge this and work
      accordingly.

PMID- 12200914
TI  - Attitudes of enuretic children towards their illness.
AB  - The aim of this study was to establish the attitudes of enuretic children towards
      their illness and to assess the correlation between children's attitudes and
      biological and medical variables describing the clinical picture and course of
      enuresis. Fifty children were included (31M, 19F), aged 8-18 y (mean 12.74 y),
      all with the diagnosis of enuresis. The reference groups consisted of 60 children
      with asthma and 40 children with chronic heart disease, aged 8-12 y. The Polish
      version of the Child Attitude Toward Illness Scale (CATIS) was administered to
      all the children and structured interviews concerning demographic and medical
      data were conducted with the parents. There were no significant differences in
      median CATIS scores between the subgroups divided according to age, type of
      enuresis and family history of enuresis. There was no significant correlation
      between the CATIS score and frequency of enuresis and number of therapeutic
      failures. The girls had significantly lower median CATIS scores than the boys (p
      = 0.03). The difference in median CATIS scores between genders was significant
      only for the older group aged 14-18 y. The older girls had the lowest CATIS
      scores. Enuretic children were found to have statistically significantly more
      negative attitudes towards their illness than children with asthma (p = 0.006)
      and children with chronic heart disease (p = 0.067). CONCLUSION: Enuretic
      children had more negative feelings about their illness than children with other
      chronic conditions. This negative attitude was not related to demographic or
      clinical data except for gender. The adolescent girls demonstrated the most
      negative attitude towards enuresis.

PMID- 12200915
TI  - Risk factors of back pain frequency in schoolchildren: a search for explanations
      to a public health problem.
AB  - This study examined physical, behavioral and social factors associated with
      schoolchildren's back pain. Factors associated with back pain were also
      identified using a stepwise regression method. The study was based on a self
      administered questionnaire survey of a random national sample of 2173 Icelandic
      11-12 and 15-16-y-old schoolchildren. It found that older subjects tended to
      report back pain more frequently than younger children. Back pain showed
      significant associations with different aspects of physical condition such as
      chronic health conditions, tiredness and physical fitness. A number of behavioral
      factors including participation in sports, television viewing, eating habits and
      smoking also had a relationship with back pain. Finally, children with lower
      social support were more likely to experience back pain. CONCLUSION: Overall,
      four major factors (age, morning tiredness, eating habits and parental support)
      emerged as factors associated with back pain in the study subjects. These results
      highlighted the roles of lifestyle and social factors in the experience of back
      pain in schoolchildren.

PMID- 12200916
TI  - Subacute hepatic failure after the perinatal period with haemochromatotic
      siderosis at the age of 11 months: an unusual perspective on neonatal
      haemochromatosis.
AB  - Neonatal haemochromatosis is a rare disease characterized by the early onset of
      liver failure, a rapidly deteriorating clinical course and high mortality. An
      unusual case is presented of subacute hepatic failure in which autopsy findings
      at the age of 11 mo showed a haemochromatotic pattern of siderosis. Despite the
      similarity in the pattern of iron distribution to neonatal haemochromatosis, the
      clinical course was highly atypical in that the infant had later and milder
      presentation at 1 mo of age and slow progression into liver failure. This case
      illustrates the heterogeneous nature of the haemochromatotic phenotype in
      newborns and infants. CONCLUSION: The entity "neonatal haemochromatosis" may
      reflect a spectrum of diseases with diverse aetiologies. Fulminant liver disease
      in the newborn period can also result in similar pattern of iron distribution.

PMID- 12200917
TI  - Validity and reliability of body composition assessed by the sulphur hexafluoride
      dilution method.
AB  - The aims of this study were to assess the validity and reliability of body volume
      and percent body fat determined by sulphur hexafluoride dilution, using
      underwater weighing as the criterion method, and to determine the influence of
      the magnitude of body volume. Thirty-one healthy Japanese individuals aged 18-27
      years (16 males: height 1.70 +/- 0.06 m, mass 64.8 +/- 7.7 kg; 15 females: height
      1.60 +/- 0.05 m, mass 55.2 +/- 6.2 kg; mean +/- s) participated in the study.
      Sulphur hexafluoride dilution measures the concentration of sulphur hexafluoride
      gas in the chamber (BSF-200, Shimazu Corp.). Underwater weighing was performed
      five times using a weight scale (AD-6204, A&D) after residual volume had been
      determined (System9, Minato Medical Corp.). There were no significant differences
      in the mean between two trials for body volume, body density or percent body fat
      determined by sulphur hexafluoride dilution. The intra-class correlation
      coefficient of these variables ranged from 0.985 to 0.999. The results suggest
      that sulphur hexafluoride dilution is a reliable method for assessing body
      composition. There was no significant difference in body volume or percent body
      fat between sulphur hexafluoride dilution (males: 61.3 +/- 7.6 litres, 18.4 +/-
      6.7%; females: 52.8 +/- 6.9 litres, 21.0 +/- 8.9%) and underwater weighing
      (males: 60.6 +/- 7.0 litres, 15.6 +/- 3.5%; females: 53.0 +/- 6.5 litres, 23.7 +/
      6.1%) and there was a high correlation between the two (r = 0.997, P < 0.05). A
      Bland-Altman plot of the difference between percent body fat estimated by
      underwater weighing and sulphur hexafluoride dilution versus average percent body
      fat by the two methods showed no systematic difference (mean difference = -0.12
      +/- 6.6 kg). The upper and lower limits of agreement were 13.2% and -13.4%,
      respectively. Determination by sulphur hexafluoride dilution resulted in both
      over- and underestimations in body volume and the difference between the two body
      volumes (determined by underwater weighing and by sulphur hexafluoride dilution)
      was inversely proportional to the mean body volume by the two methods. This
      suggests that improvements need to be made to the device or to the technique to
      maintain a constant volume of sulphur hexafluoride in the chamber.

PMID- 12200918
TI  - A study of the discomfort associated with tennis shoes.
AB  - Subjective tests based on information gathered using 'discomfort questionnaires'
      have been used widely in ergonomics. In this study, we used a similar method to
      examine the discomfort associated with the footwear worn in tennis matches. A
      sample of 146 tennis players from a population of approximately 4000 completed
      the questionnaire. We performed a descriptive analysis of the study variables.
      The associations between discomfort and pain and between discomfort and design
      errors were evaluated using cross-tabulation and chi-squared tests. We found that
      9% of players considered their footwear to be uncomfortable, 23% considered it to
      be acceptable and 68% regarded it as comfortable. Six design errors were
      identified and five body areas were reported as experiencing discomfort due to
      the footwear. Factor analysis identified four factors related to discomfort and
      six design errors. Subsequent correlation analysis identified several
      relationships among these factors. There was a strong correlation (r = 0.187, P =
      0.022) between plantar discomfort and incorrect arch support.

PMID- 12200919
TI  - Prediction of 2000 m indoor rowing performance using a 30 s sprint and maximal
      oxygen uptake.
AB  - The aim of this study was to predict indoor rowing performance in 12 competitive
      female rowers (age 21.3 +/- 3.6 years, height 1.68 +/- 0.54 m, body mass 67.1 +/-
      11.7 kg; mean +/- s) using a 30 s rowing sprint, maximal oxygen uptake and the
      blood lactate response to submaximal rowing. Blood lactate and oxygen uptake
      (VO2) were measured during a discontinuous graded exercise test on a Concept II
      rowing ergometer incremented by 25 W for each 2 min stage; the highest VO2
      measured during the test was recorded as VO2max (mean = 3.18 +/- 0.35 l.min-1).
      Peak power (380 +/- 63.2 W) and mean power (368 +/- 60.0 W) were determined using
      a modified Wingate test protocol on the Concept II rowing ergometer. Rowing
      performance was based on the results of the 2000 m indoor rowing championship in
      1997 (466.8 +/- 12.3 s). Laboratory testing was performed within 3 weeks of the
      rowing championship. Submitting mean power (Power), the highest and lowest five
      consecutive sprint power outputs (Maximal and Minimal), percent fatigue in the
      sprint test (Fatigue), VO2max (l.min-1), VO2max (ml.kg-1.min-1), VO2 at the
      lactate threshold, power at the lactate threshold (W), maximal lactate
      concentration, lactate threshold (percent VO2max) and VEmax (l.min-1) to a
      stepwise multiple regression analysis produced the following model to predict
      2000 m rowing performance: Time2000 = -0.163 (Power) -14.213.(VO2max l.min-1)
      +0.738.(Fatigue) 7.259 (R2 = 0.96, standard error = 2.89). These results indicate
      that, in the women studied, 75.7% of the variation in 2000 m indoor rowing
      performance time was predicted by peak power in a rowing Wingate test, while
      VO2max and fatigue during the Wingate test explained an additional 12.1% and 8.2%
      of the variance, respectively.

PMID- 12200920
TI  - The effects of ACL injury on quadriceps and hamstring torque, work and power.
AB  - The aim of this study was to assess isokinetic torque, work and power between non
      injured, ACL (anterior cruciate ligament)-deficient and ACL-reconstructed
      individuals. Ten healthy, non-injured individuals, seven unilateral ACL-deficient
      individuals and six unilateral ACL-reconstructed individuals were assessed for
      isokinetic quadriceps and hamstring strength at 1.05 and 3.14 rad.s-1. Peak
      torque, total work, average power and the ratio of peak torque to body mass were
      computed for both velocities. Peak torque was also corrected for body mass, using
      allometric modelling. The non-injured individuals showed significantly greater
      quadriceps peak torque to body mass ratios than the ACL-deficient and ACL
      reconstructed individuals at both velocities, and greater hamstring peak torque
      to body mass ratios than the ACL-deficient group at 3.14 rad.s-1 (P < 0.05). The
      ACL-deficient individuals displayed greater quadriceps and hamstring peak torque,
      total work and average power than the non-injured individuals at 1.05 rad.s-1 (P
      < 0.05). The ACL-deficient individuals also displayed significantly greater peak
      torque, total work and average power than the ACL-reconstructed individuals for
      the quadriceps at both velocities (P < 0.05). The ACL-deficient individuals
      demonstrated greater hamstring peak torque and total work than the non-injured
      individuals at both velocities (P < 0.05). The allometrically modelled peak
      torques at both isokinetic velocities demonstrated that the quadriceps muscle
      values were significantly higher in the non-involved than the involved limb. The
      hamstring peak torques corrected for body mass were significantly higher in the
      non-involved than the involved limb only at 1.05 rad.s-1. The main finding from
      the present study is that isokinetic measures in ratio-scaled or absolute units
      yield a different outcome and, hence, interpretation compared with the allometric
      approach.

PMID- 12200921
TI  - Pre-competition imagery, self-efficacy and performance in collegiate golfers.
AB  - In this study, we examined the relationships between self-efficacy, pre
      competition imagery use and performance. A modified version of the Sport Imagery
      Questionnaire was used to assess both the motivational and cognitive functions of
      imagery used by 51 varsity golfers during the hour before a Provincial University
      Golf Championship. In line with Martin and co-workers' model of imagery use in
      sport, we hypothesized that self-efficacy would be positively related to
      motivational general-mastery imagery use and motivational general-mastery imagery
      use would be predictive of golf performance. Also, consistent with theorizing by
      Bandura, we hypothesized that self-efficacy would predict golf performance, but
      that the relationship between self-efficacy and performance would be mediated by
      imagery use. The results of hierarchical multiple regression analyses revealed
      that pre-competition motivational general-mastery imagery accounted for
      significant variance in both self-efficacy (adjusted R2 = 0.26, P < 0.01) and
      performance (adjusted R2 = 0.31, P < 0.01). The results also indicated that self
      efficacy was predictive of golf performance and that motivational general-mastery
      imagery use mediated the relationship between self-efficacy and performance. The
      results are discussed in relation to athletes' pre-competition preparation and
      intervention.

PMID- 12200922
TI  - Cognitive interference during competition among volleyball players with different
      goal orientation profiles.
AB  - In this study, we examined interfering thoughts during sport competition among
      university volleyball players as a function of dominant goal orientation and
      outcome. In particular, we investigated the performance worries and thoughts of
      escape experienced while performing in athletes with high task and low ego
      orientation and athletes with high ego and low task orientation. Goal
      orientations were assessed before the start of a volleyball tournament, whereas
      cognitive interference was assessed on three different occasions after games. The
      results revealed no consistent differences for performance worries. In contrast,
      in all analyses we found that athletes with high ego and low task orientations
      reported more thoughts of escape when losing than when winning, and more thoughts
      of escape than athletes with high task and low ego orientations when winning or
      losing. The results support in part the suggestion that a high ego orientation,
      when not accompanied by a high task orientation, can be linked to motivationally
      maladaptive cognitions.

PMID- 12200923
TI  - Anthropometric fractionation of body mass: Matiegka revisited.
AB  - In a group of 699 Belgian nursing professionals, we estimated body composition
      using the four-component anthropometric model, relying on the equations
      originally formulated by Matiegka in 1921 and later revised by Drinkwater and
      colleagues. We estimated muscle mass using the more recent formula proposed by
      Martin and co-workers. A discrepancy was noted between estimated total body mass
      and 'assessed' mass, suggesting erroneous estimations of the components.

PMID- 12200924
TI  - Exercise does not necessarily influence the phase of the circadian rhythm in
      temperature in healthy humans.
AB  - Seventeen healthy adults exercised for 30 min (70% VO2max), at different times of
      the day and night throughout a 24 h period. The effect on the phase of core
      temperature rhythm was assessed by comparing the rhythms on the day immediately
      before and immediately after the day of exercise with the participants living
      normally on these 2 days. Assessments were made upon data that had been corrected
      for the thermogenic effects of sleep and activity. When exercise was performed in
      the period between 4 h before and 1 h after the temperature minimum, there was a
      phase delay of 1.03 +/- 0.78 h (mean +/- s; n = 6); when performed between 3 and
      8 h after the temperature minimum, there was a phase advance of 1.07 +/- 1.23 h
      (n = 9). Both means were significantly different from zero (Student's one-sample
      t-tests: P < 0.05). Performed at other times, exercise had no significant effect
      on the phase of the temperature rhythm. The phase changes were not significantly
      different from those previously observed by us in sedentary individuals exposed
      to domestic lighting. We conclude that the amount of physical activity has very
      little effect on the body clock.

PMID- 12200925
TI  - Segmented multiple plane reconstruction: a novel approximate reconstruction
      scheme for multi-slice spiral CT.
AB  - A new reconstruction scheme for multi-row spiral CT is described and results are
      presented. The spiral path is decomposed into small, overlapping segments which
      are used for a separate convolution and backprojection yielding a stack of
      segment images which contain only projection data of a partial scan (typically in
      the range of 20). These segment image stacks are, in a second step, reformatted
      to the requested image planes. In a third step, the reformatted segment images
      are added to obtain full images. The main benefit of the proposed algorithm is
      superior images quality. A 64-row dataset with a cone angle of 6.4 and a table
      feed of 80 mm per spiral turn has been reconstructed with excellent image
      quality. A filter direction for three-dimensional (3D) backprojection algorithms
      is suggested by investigating the limit where the partial scan size goes to zero.

PMID- 12200926
TI  - Analysis of an exact inversion algorithm for spiral cone-beam CT.
AB  - In this paper we continue studying a theoretically exact filtered backprojection
      inversion formula for cone beam spiral CT proposed earlier by the author. Our
      results show that if the phantom f is constant along the axial direction, the
      formula is equivalent to the 2D Radon transform inversion. Also, the inversion
      formula remains exact as spiral pitch goes to zero and in the limit becomes again
      the 2D Radon transform inversion formula. Finally, we show that according to the
      formula the processed cone beam projections should be backprojected using both
      the inverse distance squared law and the inverse distance law.

PMID- 12200927
TI  - An accurate iterative reconstruction algorithm for sparse objects: application to
      3D blood vessel reconstruction from a limited number of projections.
AB  - Based on the duality of nonlinear programming, this paper proposes an accurate
      row-action type iterative algorithm which is appropriate to reconstruct sparse
      objects from a limited number of projections. The cost function we use is the Lp
      norm with p approximately 1.1. This norm allows us to pick up a sparse solution
      from a set of feasible solutions to the measurement equation. Furthermore, since
      it is both strictly convex and differentiable, we can use the duality of
      nonlinear programming to construct a row-action type iterative algorithm to find
      a solution. We also impose the bound constraint on pixel values to pick up a
      better solution. We demonstrate that this method works well in three-dimensional
      blood vessel reconstruction from a limited number of cone beam projections.

PMID- 12200928
TI  - Iterative reconstruction methods for high-throughput PET tomographs.
AB  - A fast iterative method is described for processing clinical PET scans acquired
      in three dimensions, that is, with no inter-plane septa, using standard computers
      to replace dedicated processors used until the late 1990s. The method is based on
      sinogram resampling, Fourier rebinning, Monte Carlo scatter simulation and
      iterative reconstruction using the attenuation-weighted OSEM method and a
      projector based on a Gaussian pixel model. Resampling of measured sinogram values
      occurs before Fourier rebinning, to minimize parallax and geometric distortions
      due to the circular geometry, and also to reduce the size of the sinogram. We
      analyse the geometrical and statistical effects of resampling, showing that the
      lines of response are positioned correctly and that resampling is equivalent to
      about 4 mm of post-reconstruction filtering. We also present phantom and patient
      results. In this approach, multi-bed clinical oncology scans can be ready for
      diagnosis within minutes.

PMID- 12200929
TI  - Consistency conditions upon 3D CT data and the wave equation.
AB  - Source trajectories and reconstruction algorithms for clinical volumetric
      computerized tomography (VCT) will require optimization for efficiency and image
      quality. VCT data is highly overdetermined, satisfying an ultrahyperbolic partial
      differential equation. Characteristic boundary value problems for the hyperbolic
      wave equation and ultrahyperbolic equation are compared, focusing in this paper
      on a mathematically instructive open-gantry VCT geometry. This example provides
      physical insight into consistency conditions upon VCT data, clearly showing which
      information about the object can and cannot be recovered from a set of measured
      projections. Furthermore, this example demonstrates that efficient numerical
      solvers for the ultrahyperbolic equation can provide tremendous flexibility in
      the choice of reconstruction algorithm.

PMID- 12200930
TI  - HeinzelCluster: accelerated reconstruction for FORE and OSEM3D.
AB  - Using iterative three-dimensional (3D) reconstruction techniques for
      reconstruction of positron emission tomography (PET) is not feasible on most
      single-processor machines due to the excessive computing time needed, especially
      so for the large sinogram sizes of our high-resolution research tomograph (HRRT).
      In our first approach to speed up reconstruction time we transform the 3D scan
      into the format of a two-dimensional (2D) scan with sinograms that can be
      reconstructed independently using Fourier rebinning (FORE) and a fast 2D
      reconstruction method. On our dedicated reconstruction cluster (seven four
      processor systems, Intel PIII@700 MHz, switched fast ethernet and Myrinet,
      Windows NT Server), we process these 2D sinograms in parallel. We have achieved a
      speedup > 23 using 26 processors and also compared results for different
      communication methods (RPC, Syngo, Myrinet GM). The other approach is to
      parallelize OSEM3D (implementation of C Michel), which has produced the best
      results for HRRT data so far and is more suitable for an adequate treatment of
      the sinogram gaps that result from the detector geometry of the HRRT. We have
      implemented two levels of parallelization for four dedicated cluster (a shared
      memory fine-grain level on each node utilizing all four processors and a coarse
      grain level allowing for 15 nodes) reducing the time for one core iteration from
      over 7 h to about 35 min.

PMID- 12200931
TI  - Effects of temporal modelling on the statistical uncertainty of spatiotemporal
      distributions estimated directly from dynamic SPECT projections.
AB  - Artefacts can result when reconstructing a dynamic image sequence from
      inconsistent single photon emission computed tomography (SPECT) projection data
      acquired by a slowly rotating gantry. The artefacts can lead to biases in kinetic
      parameters estimated from time-activity curves generated by overlaying volumes of
      interest on the images. Insufficient sampling and truncation of projections by
      cone-beam collimators can cause additional artefacts. To overcome these sources
      of bias in conventional image based dynamic data analysis, we have been
      investigating the estimation of time-activity curves and kinetic model parameters
      directly from dynamic SPECT projection data by modelling the spatial and temporal
      distribution of the radiopharmaceutical throughout the projected field of view.
      In the present work, we perform Monte Carlo simulations to study the effects of
      the temporal modelling on the statistical variability of the reconstructed
      spatiotemporal distributions. The simulations utilize fast methods for fully four
      dimensional (4D) direct estimation of spatiotemporal distributions and their
      statistical uncertainties, using a spatial segmentation and temporal B-splines.
      The simulation results suggest that there is benefit in modelling higher orders
      of temporal spline continuity. In addition, the accuracy of the time modelling
      can be increased substantially without unduly increasing the statistical
      uncertainty, by using relatively fine initial time sampling to capture rapidly
      changing activity distributions.

PMID- 12200932
TI  - Filtering point spread function in backprojection cone-beam CT and its
      applications in long object imaging.
AB  - In backprojection cone-beam CT the cone-beam projection images are first
      filtered, then 3D backprojected into the object space. In this paper the point
      spread function (PSF) for the filtering operation is studied. For the cases where
      the normalization matrix is a constant, i.e. all integration planes intersect the
      scan path the same number of times, the derivation of the PSF is extended to the
      general case of limited angular range for the Radon line integrals. It is found
      that the 2D component of the PSF can be reduced to the form of space-variant 1D
      Hilbert transforms. The application of the PSF to a number of aspects in long
      object imaging will be discussed.

PMID- 12200933
TI  - Implementation of continuous 3D whole-body PET scanning using on-the-fly Fourier
      rebinning.
AB  - The continuous scanning mode in three-dimensional (3D) whole-body PET studies has
      the advantage of axial sensitivity uniformity over the majority of the axial FOV.
      However, this scan mode requires large data handling compared to conventional
      discrete scans. In this work, we have implemented and evaluated a new continuous
      3D scan method using 'on-the-fly' Fourier rebinning. In this method, sinograms
      for the pair of rings are added in real-time into the sinograms of the
      incremented ring pairs by moving the bed axially one detector width at a time.
      For an N-ring scanner, 2N--1 sinograms are transferred to a host computer at each
      bed position and rebinned into direct two-dimensional (2D) sinograms using
      Fourier rebinning. Phantom and human studies showed that the axial image
      uniformity is achieved without degrading the axial resolution. This method can
      minimize the time for off-line data processing and makes the continuous 3D scan
      more feasible in clinical whole-body studies.

PMID- 12200935
TI  - Inversion of the 3D exponential x-ray transform for a half equatorial band and
      other semi-circular geometries.
AB  - This work presents new mathematical results on the inversion of the exponential x
      ray transform. It is shown that a reconstruction formula can be obtained for any
      dataset whose projection directions consist of a union of half great circles on
      the unit sphere. A basic example of such a dataset is the semi-equatorial band.
      The discussion in the paper is mostly focused on this example. The reconstruction
      formula takes the form of a Neumann (geometric) series and is both exact and
      stable. The exponential x-ray transform has been mainly studied in SPECT imaging.
      In this context, our results demonstrate mathematically that fully 3D image
      reconstruction in SPECT with non-zero attenuation does not always require
      symmetric datasets (opposing views).

PMID- 12200934
TI  - Exact inversion of the exponential x-ray transform for rotating slant-hole (RSH)
      SPECT.
AB  - The RSH SPECT scanner provides parallel-beam attenuated projections for a fully
      3D acquisition geometry. The geometry can be represented by circles on the unit
      sphere of projection directions, one circle for each position of the detector
      head. Unlike most other fully 3D geometries this one is particularly challenging
      because there are no 2D subsets in the data. When no attenuation is present, it
      is well known that an unmeasured projection can be synthesized if it lies inside
      one of the measured circles. The main result of this work is that under some
      assumptions on the attenuation distribution, attenuated projections within a
      circle can be synthesized from available attenuated projections. One consequence
      is that RSH SPECT projections can be rebinned into a conventional SPECT geometry
      for which analytic attenuation correction techniques are available.

PMID- 12200936
TI  - Diffusion tensor MR imaging of principal directions: a tensor tomography
      approach.
AB  - A novel approach to reconstructing the principal directions of a diffusion tensor
      field directly from magnetic resonance imaging (MRI) data using a tensor
      tomography data acquisition approach was developed. If tensor eigenvalues are
      assumed to be known, the reconstruction of principal directions requires fewer
      measurements than the reconstruction of the full tensor field. The tensor
      tomography data acquisition method (rotating diffusion gradients) leads to a
      unique reconstruction of principal directions, whereas the conventional MRI
      acquisition technique (stationary diffusion gradients) leads to an ambiguous
      reconstruction of principal directions when the same number of measurements are
      used. A computer-generated phantom was used to simulate the diffusion tensor
      field in the mid-ventricular region of the myocardium. The principal directions
      of the diffusion tensor field were assumed to align with the fibre structure of
      the myocardium. An iterative algorithm was used to reconstruct the principal
      directions. Computer simulations verify that the proposed method provides
      accurate reconstruction of the principal directions of a diffusion tensor field.

PMID- 12200937
TI  - Scatter correction for positron emission mammography.
AB  - In this paper we present a scatter correction method for a regularized list mode
      maximum likelihood reconstruction algorithm for the positron emission mammograph
      (PEM) that is being developed at our laboratory. The scatter events inside the
      object are modelled as additive Poisson random variables in the forward model of
      the reconstruction algorithm. The mean scatter sinogram is estimated using a
      Monte Carlo simulation program. With the assumption that the background activity
      is nearly uniform, the Monte Carlo scatter simulation only needs to run once for
      each PEM configuration. This saves computation time. The crystal scatters are
      modelled as a shift-invariant blurring in image domain because they are more
      localized. Thus, the useful information in the crystal scatters can be
      deconvolved in high-resolution reconstructions. The propagation of the noise from
      the estimated scatter sinogram into the reconstruction is analysed theoretically.
      The results provide an easy way to calculate the required number of events in the
      Monte Carlo scatter simulation for a given noise level in the image. The analysis
      is also applicable to other scatter estimation methods, provided that the
      covariance of the estimated scatter sinogram is available.

PMID- 12200938
TI  - Model-based normalization for iterative 3D PET image reconstruction.
AB  - We describe a method for normalization in 3D PET for use with maximum a
      posteriori (MAP) or other iterative model-based image reconstruction methods.
      This approach is an extension of previous factored normalization methods in which
      we include separate factors for detector sensitivity, geometric response, block
      effects and deadtime. Since our MAP reconstruction approach already models some
      of the geometric factors in the forward projection, the normalization factors
      must be modified to account only for effects not already included in the model.
      We describe a maximum likelihood approach to joint estimation of the count-rate
      independent normalization factors, which we apply to data from a uniform
      cylindrical source. We then compute block-wise and block-profile deadtime
      correction factors using singles and coincidence data, respectively, from a
      multiframe cylindrical source. We have applied this method for reconstruction of
      data from the Concorde microPET P4 scanner. Quantitative evaluation of this
      method using well-counter measurements of activity in a multicompartment phantom
      compares favourably with normalization based directly on cylindrical source
      measurements.

PMID- 12200939
TI  - Internet2-based 3D PET image reconstruction using a PC cluster.
AB  - We describe an approach to fast iterative reconstruction from fully three
      dimensional (3D) PET data using a network of PentiumIII PCs configured as a
      Beowulf cluster. To facilitate the use of this system, we have developed a
      browser-based interface using Java. The system compresses PET data on the user's
      machine, sends these data over a network, and instructs the PC cluster to
      reconstruct the image. The cluster implements a parallelized version of our
      preconditioned conjugate gradient method for fully 3D MAP image reconstruction.
      We report on the speed-up factors using the Beowulf approach and the impacts of
      communication latencies in the local cluster network and the network connection
      between the user's machine and our PC cluster.

PMID- 12200940
TI  - Pitch dependence of longitudinal sampling and aliasing effects in multi-slice
      helical computed tomography (CT).
AB  - In this work, we investigate longitudinal sampling and aliasing effects in multi
      slice helical CT. We demonstrate that longitudinal aliasing can be a significant,
      complicated, and potentially detrimental effect in multi-slice helical CT
      reconstructions. Multi-slice helical CT scans are generally undersampled
      longitudinally for all pitches of clinical interest, and the resulting aliasing
      effects are spatially variant. As in the single-slice case, aliasing is shown to
      be negligible at the isocentre for circularly symmetric objects due to a
      fortuitous aliasing cancellation phenomenon. However, away from the isocentre,
      aliasing effects can be significant, spatially variant, and highly pitch
      dependent. This implies that measures more sophisticated than isocentre slice
      sensitivity profiles are needed to characterize longitudinal properties of multi
      slice helical CT systems. Such measures are particularly important in assessing
      the question of whether there are preferred pitches in helical CT. Previous
      analyses have generally focused only on isocentre sampling patterns, and our more
      global analysis leads to somewhat different conclusions than have been reached
      before, suggesting that pitches 3, 4, 5, and 6 are favourable, and that half
      integer pitches are somewhat suboptimal.

PMID- 12200941
TI  - Short-scan SPECT imaging with non-uniform attenuation and 3D distance-dependent
      spatial resolution.
AB  - Image quality and quantitative accuracy in single-photon emission computed
      tomography (SPECT) can be degraded by, e.g., the effects of photon attenuation
      and finite spatial resolution. It is generally considered that adequate
      compensation for such effects on SPECT images requires data acquired over 2 pi.
      Recently, using the existing consistency condition on the data function, Noo and
      Wagner (2001 Inverse Problems 17 1357-72) have shown analytically that data
      acquired over only pi can be used to correct completely for the effect of uniform
      attenuation in SPECT. It remains unknown, however, whether data acquired only
      over pi in SPECT with non-uniform attenuation and/or 3D distance-dependent
      spatial resolution (DDSR) contain complete information for accurate image
      reconstruction. In this work, we develop a heuristic perspective, which is
      referred to as the potato peeler perspective to show conceptually that data in
      SPECT with non-uniform attenuation and/or 3D DDSR acquired over 2 pi contain
      redundant information and that such information can be used to reduce the
      scanning angle in SPECT. Specifically, we show heuristically that, in SPECT with
      only non-uniform attenuation, the scanning angle can be reduced from 2 pi to pi
      and that, in SPECT with both non-uniform attenuation and DDSR with a physically
      realistic form, the scanning angle can be reduced from 2 pi to pi in a practical
      sense. We conduct computer simulation studies, and the results from these studies
      corroborate the observations obtained based upon the heuristic potato peeler
      perspective.

PMID- 12200942
TI  - Transcranial cerebral oximetry, transcranial Doppler sonography, and heart rate
      variability: useful neuromonitoring tools in anaesthesia and intensive care?

PMID- 12200943
TI  - Isoprostanes--markers of ischaemia reperfusion injury.
AB  - Ischaemia reperfusion injury is a common and important phenomenon that occurs
      predictably in patients undergoing such procedures as cardiopulmonary bypass,
      thrombolysis, surgery under tourniquet, organ transplantation or embolectomy.
      Oxidative stress and the resulting lipid peroxidation play a major role in
      reperfusion injury. Membrane and cellular dysfunction result and, subsequently,
      organ injury or failure may ensue. Traditional methods of quantifying ischaemia
      reperfusion injury, including measurement of malondialdehyde, lack specificity
      and sensitivity. It was reported in 1990 that isoprostanes, a series of
      prostaglandin-like compounds, are produced by the free radical-catalyzed
      peroxidation of arachidonic acid. Measurement of the isoprostane concentration in
      urine or plasma provides the most reliable, non-invasive method currently
      available to assess oxidative stress in vivo. Serial measurement of isoprostanes
      in biological fluids has enhanced our understanding of the mechanisms underlying
      ischaemia reperfusion injury itself and its role in certain diseases.
      Furthermore, measurement of the isoprostane concentration provides a means to
      assess the effects of prophylactic and therapeutic interventions. In the future,
      the development of rapid, simple assays for isoprostanes offers the potential to
      assess prognosis during and after ischaemia reperfusion events.

PMID- 12200944
TI  - Impact of the reduction of anaesthesia turnover time on operating room
      efficiency.
AB  - BACKGROUND AND OBJECTIVE: We investigated whether an increase in anaesthesia
      staffing to permit induction of anaesthesia before the previous case had ended
      ('overlapping') would increase overall efficiency in the operating room.
      Hitherto, the average duration of operating sessions was too long, thus impeding
      the timely commencement of physicians' ward duties. METHODS: The investigation
      was designed as a prospective, non-randomized, interrupted time-series analysis
      divided into three phases: (a) a baseline of 3.5 months, (b) a 2.5 month
      intervention phase, in which anaesthesia staffing was increased by one attending
      physician and one nurse, and (c) a further 2 months under baseline conditions.
      Data focussed on process management were collected from operating room staff,
      anaesthesia personnel and surgeons using a structured questionnaire collected
      daily during the entire study. RESULTS: Turnover time between consecutive
      operations decreased from 65 to 52 min per operation (95% CI: 9; 17; P = 0.0001).
      Operating room occupancy increased from 4:28 to 5:27 h day-1 (95% CI: 50; 68; P =
      0.005). The surgeons began their work on the ward 35 min (95% CI: 30; 40) later
      than before the intervention and their overtime increased from 22:36 to 139:50 h.
      CONCLUSIONS: The time between surgical operations decreased significantly.
      Increased operating room efficiency owing to overlapping induction of anaesthesia
      allows more intense scheduling of operations. Thus, physicians and nurses can be
      released to spend more time with their patients in the ward. Improving the
      efficiency of the operating room alone is insufficient to improve human resource
      management at all levels of a surgical clinic.

PMID- 12200945
TI  - Lidocaine-induced cell death in a human model of neuronal apoptosis.
AB  - BACKGROUND AND OBJECTIVE: Clinical studies suggest that lidocaine may induce
      irreversible neurological damage after spinal application in human beings. The
      mechanisms underlying the possible cytotoxic action of lidocaine have only been
      suggested from animal studies. This study aimed to investigate if lidocaine
      exhibited cytotoxic action in a human model widely used for the study of neuronal
      apoptosis. This is important to know as it may help one to judge on possible
      neurotoxic risks imposed by the spinal application of lidocaine. METHODS: The
      concentration- and time-dependent effects of lidocaine on retinoic acid
      differentiated human neuroblastoma SH-SY5Y cells were quantified by trypan blue
      staining, the release of lactate dehydrogenase, immunocytochemistry and flow
      cytometry. RESULTS: The local anaesthetic caused a significant increase in the
      number of cells staining positive for trypan blue, a significant increase of LDH
      release into the incubation medium, and a significant increase of 7AAD and
      annexin V binding. Lidocaine induced apoptosis already at 3 mm. At a
      concentration of 10 mmol 47% of the cells and at 30 mmol 98% of the cell
      population was necrotic. Both necrosis and apoptosis were time-dependent.
      CONCLUSIONS: The results demonstrate that lidocaine exhibited neurotoxic effects
      in a human model established for the study of drug-induced neuronal apoptosis.
      The results were consistent with the neurotoxic clinical effects of lidocaine.
      These effects may be produced by more than a single mechanism.

PMID- 12200946
TI  - Voltage-dependent block of neuronal and skeletal muscle sodium channels by thymol
      and menthol.
AB  - BACKGROUND AND OBJECTIVE: Thymol is a naturally occurring phenol derivative used
      in anaesthetic practice as a stabilizer and preservative of halothane, usually at
      a concentration of 0.01%. Although analgesic effects have long been described for
      thymol and its structural homologue menthol, a molecular basis for these effects
      is still lacking. We studied the blocking effects of thymol and menthol on
      voltage-activated sodium currents in vitro as possible molecular target sites.
      METHODS: Whole cell sodium inward currents via heterologously (HEK293 cells)
      expressed rat neuronal (rat type IIA) and human skeletal muscle (hSkM1) sodium
      channels were recorded in the absence and presence of definite concentrations of
      either thymol or menthol. RESULTS: When depolarizing pulses to 0 mV were started
      from a holding potential of -70 mV, half-maximum blocking concentrations (IC50)
      for the skeletal muscle and the neuronal sodium channel were 104 and 149 mumol
      for thymol and 376 and 571 mumol for menthol. The blocking potency of both
      compounds increased at depolarized holding potentials with the fraction of
      inactivated channels. The estimated dissociation constant Kd for thymol and
      menthol from the inactivated state was 22 and 106 mumol for the neuronal and 23
      and 97 mumol for the skeletal muscle sodium channel, respectively. CONCLUSIONS:
      The results suggest that antinociceptive and local anaesthetic effects of thymol
      and menthol might be mediated via blockade of voltage-operated sodium channels
      with the phenol derivative thymol being as potent as the local anaesthetic
      lidocaine.

PMID- 12200947
TI  - Target-controlled propofol requirements at induction of anaesthesia: effect of
      remifentanil and midazolam.
AB  - BACKGROUND AND OBJECTIVE: Target-controlled infusions of anaesthetic agents have
      become increasingly available. They can involve the use of propofol in
      combination with an opioid or a benzodiazepine. The effect site concentration of
      propofol infusions has been advocated as a method of estimating drug
      distribution. We investigated the influence of co-induction with remifentanil and
      midazolam on effect site propofol requirements at induction of anaesthesia using
      target-controlled infusions. METHODS: Sixty-six consenting adult patients were
      randomly allocated to three treatment groups. Each group received induction of
      anaesthesia with a different total intravenous technique. One group was induced
      with target-controlled propofol alone; another received target-controlled
      propofol and target-controlled remifentanil (3 ng mL-1); and the last received
      midazolam (0.03 mg kg-1), target-controlled remifentanil (3 ng mL-1) and target
      controlled propofol. Computer simulation was used to calculate effect site
      concentrations. We recorded propofol dose and effect site concentration at loss
      of verbal response. RESULTS: The effect site concentration (Ce50) of propofol
      alone was 2.19 micrograms mL-1. This was reduced to 1.55 micrograms mL-1 during
      co-induction with remifentanil and further reduced to 0.64 microgram mL-1 with
      midazolam premedication (P < 0.001; ANOVA). CONCLUSIONS: We conclude that co
      induction with remifentanil alone or with midazolam can be used to reduce
      propofol doses at induction of anaesthesia using target-controlled infusions. We
      believe that using effect site concentration may prove a useful tool in routine
      clinical practice.

PMID- 12200948
TI  - Using the Sustained Attention to Response Test to detect cognitive dysfunction
      after day case surgery.
AB  - BACKGROUND AND OBJECTIVE: Cognitive dysfunction has been reported after general
      anaesthesia, but its assessment is time consuming and difficult to evaluate. This
      pilot study assessed the feasibility of using the Sustained Attention to Response
      Test to assess 35 ASA I-II adults (mean age 31.6 yr) undergoing day case surgery
      under general anaesthesia, and 25 ASA I-II adults (mean age 47.8 yr) undergoing
      day case surgery under local anaesthesia. METHODS: The Sustained Attention to
      Response Test was performed before surgery and repeated 2 h after surgery.
      RESULTS: When patients repeated the test after surgery under local anaesthesia,
      the number of incorrect responses increased, but reaction times decreased (P <
      0.05). Following general anaesthesia, the number of incorrect responses increased
      (P < 0.05), but reaction times remained unchanged. CONCLUSIONS: The Sustained
      Attention to Response Test is simple to administer and may be a useful tool when
      comparing different anaesthetic techniques and their effects on postoperative
      deficits in sustained attention.

PMID- 12200949
TI  - Anaesthetic and postoperative analgesic effects of spinal clonidine as an
      additive to prilocaine in the transurethral resection of urinary bladder tumours.
AB  - BACKGROUND AND OBJECTIVE: The alpha 2-adrenoceptor agonist clonidine has potent
      central antinociceptive properties. The study was designed to investigate the
      effects of the combined subarachnoid administration of clonidine and prilocaine
      on spinal block and postoperative analgesia for the transurethral resection of
      tumours in the urinary bladder. METHODS: The controlled, prospective, double
      blind study enrolled 40 patients scheduled for elective transurethral resection
      of bladder tumours under spinal anaesthesia with prilocaine. Patients were
      randomly assigned to receive an intrathecal injection of prilocaine 75 mg alone
      (control group) or in combination with clonidine 75 micrograms. We assessed
      haemodynamic changes (non-invasive arterial pressure, heart rate), pulse
      oximetry, the upper level of block, the onset and duration of sensory and motor
      block, postoperative analgesia and any adverse effects. RESULTS: There were no
      statistically significant differences in demographic data, heart rate, onset time
      or the levels of sensory or motor block. Analgesia lasted significantly longer in
      the clonidine group (498.4 +/- 226.9 versus 187.2 +/- 103.1 min; P < 0.05). The
      duration of motor block was longer in the clonidine group (165.5 +/- 30.6 min)
      than in the control group (139.7 +/- 40.4 min; P < 0.05) and the duration of
      sensory block was also longer in the clonidine group (157.3 +/- 24.5 min) than in
      the control group (137.2 +/- 31.2 min; P < 0.05). Fewer patients in the recovery
      room needed metamizol (dipyrone) in the clonidine group (5%) than in the control
      group (50%). Arterial pressure decreased significantly in the clonidine group 75
      135 min after the block. CONCLUSIONS: The addition of clonidine 75 micrograms to
      prilocaine 75 mg for subarachnoid anaesthesia increased the duration of sensory
      and motor block and reduced the need for additional postoperative analgesics by
      providing excellent analgesia for about 8 h during recovery from transurethral
      resection of bladder tumours.

PMID- 12200950
TI  - Spinal block or total intravenous anaesthesia with propofol and remifentanil for
      gynaecological outpatient procedures.
AB  - BACKGROUND AND OBJECTIVE: The aim of this prospective, randomized study was to
      compare the preparation and discharge times, the side-effects and patient
      satisfaction after gynaecological outpatient procedures performed using either
      spinal block or total intravenous anaesthesia with propofol and remifentanil.
      METHODS: With Ethics Committee approval and written informed consent, 40 healthy
      females scheduled for hysteroscopic ablation of endometrial neoplasm were
      randomly allocated to receive either a spinal block with bupivacaine 0.5%
      hyperbaric solution 10 mg (n = 20) or total intravenous anaesthesia with propofol
      and remifentanil (n = 20). Preparation and discharge times, as well as occurrence
      of untoward events and anaesthesia-related costs, were recorded. RESULTS: The
      median (range) preparation time was 7 (7-10) min with general anaesthesia, and 11
      (7-21) min with spinal block (P = 0.00005). No differences in discharge time from
      the postanaesthesia care unit and incidence of hypotension or bradycardia, or
      both, were reported between the two groups. Hospital discharge times were 156
      (101-345) min after general anaesthesia and 296 (195-720) min after spinal
      anaesthesia (P = 0.0005). Acceptance of the anaesthesia technique was better
      after general (100%) than after spinal anaesthesia (75%) (P = 0.04). No
      differences in total costs were reported between spinal block ([symbol: see text]
      155 ([symbol: see text] 117-[symbol: see text] 224)) and propofol-remifentanil
      general anaesthesia ([symbol: see text] 143 ([symbol: see text] 124-[symbol: see
      text] 203) (P = 0.125)). CONCLUSIONS: Accurate titration of short-acting
      intravenous anaesthetic drugs such as propofol and remifentanil results in
      shorter preparation times and earlier home discharge after outpatient
      gynaecological procedures compared with spinal anaesthesia with hyperbaric
      bupivacaine 10 mg, with better patient acceptance and no increased costs.

PMID- 12200951
TI  - Decrease in minimum alveolar concentration of sevoflurane during anaesthesia and
      arthroscopy.
AB  - BACKGROUND AND OBJECTIVE: Although the MACtetanus (minimum alveolar concentration
      that prevents movement in response to electrical tetanus stimulation in 50% of
      patients) of isoflurane decreases during anaesthesia and surgery, it is not known
      whether this occurs to the same extent with other inhalational anaesthetics. We
      determined the MACtetanus of sevoflurane before and after surgery. METHODS:
      Eleven patients who underwent arthroscopy of the shoulder underwent inhalational
      induction of anaesthesia with sevoflurane and tracheal intubation by
      succinylcholine. MACtetanus was determined in each patient by testing the
      response to a 10 s, 50 Hz, 80 mA transcutaneous tetanic electrical stimulus to
      the ulnar nerve at varying concentrations of sevoflurane. The end-tidal
      concentration of sevoflurane was kept constant for 15 min before each stimulus
      and the concentration of sevoflurane varied in increments of 0.1% until a
      sequence of three alternate responses (move, not move, move) or (not move, move,
      not move) was obtained. After arthroscopy of the shoulder, individual MACtetanus
      were measured as described above. RESULTS: The mean MACtetanus decreased from
      2.22 +/- 0.29% before arthroscopy to 1.82 +/- 0.26% after arthroscopy (P < 0.01).
      CONCLUSIONS: It is concluded that the MACtetanus of sevoflurane decreases during
      anaesthesia and surgery.

PMID- 12200952
TI  - Effects of chronic occupational exposure to anaesthetic gases on the rate of
      neutrophil apoptosis among anaesthetists.
AB  - BACKGROUND AND OBJECTIVE: Volatile anaesthetic agents are known to influence
      neutrophil function. The aim was to determine the effect of chronic occupational
      exposure to volatile anaesthetic agents on the rate of neutrophil apoptosis among
      anaesthetists. To test this hypothesis, we compared the rate of neutrophil
      apoptosis in anaesthetists who had been chronically exposed to volatile
      anaesthetic agents with that in unexposed volunteers. METHODS: Venous blood (20
      mL) was withdrawn from 24 ASA I-II volunteers, from which neutrophils were
      isolated, and maintained in culture. At 1, 12 and 24 h in culture, the percentage
      of neutrophil apoptosis was assessed by dual staining with annexin V-FITC and
      propidium iodide. RESULTS: At 1 h (but not at 12 and 24 h) in culture, the rate
      of neutrophil apoptosis was significantly less in the anaesthetists--13.8 (12.9%)
      versus 34.4 (12.1%) (P = 0.001). CONCLUSIONS: Chronic occupational exposure to
      volatile anaesthetic agents may inhibit neutrophil apoptosis. This may have
      implications for anaesthetists and similarly exposed healthcare workers in terms
      of the adequacy of their inflammatory response.

PMID- 12200953
TI  - Effects of sodium nitroprusside-induced controlled hypotension on pancreatic
      function assessed by pancreatitis-associated protein in patients undergoing
      radical prostatectomy.
AB  - BACKGROUND AND OBJECTIVE: Controlled hypotension may alter organ blood flow and
      tissue oxygenation. The aim of the study was to investigate whether induced
      hypotension using sodium nitroprusside alters pancreatic function assessed by
      pancreatitis-associated protein concentrations in the blood. METHODS: Thirty
      patients undergoing elective radical prostatectomy were allocated randomly into
      two groups: (a) hypotension group: sodium nitroprusside was administered to lower
      mean arterial pressure to approximately 50 mmHg; (b) control group: no
      hypotension was used, mean arterial pressure was kept > 70 mmHg. Pancreatitis
      associated protein and lipase were measured in arterial blood samples: after
      induction of anaesthesia (T1), at the end of surgery (T2), 2 h (T3) and 24 h (T4)
      postoperatively. RESULTS: Pancreatitis-associated protein plasma concentrations
      increased significantly in patients in the hypotensive group (from 2.8 +/- 1.1 to
      5.5 +/- 2.0 micrograms L-1 at T4) and pancreatitis-associated protein plasma
      concentrations were significantly higher in comparison with controls (5.5 +/- 2.0
      versus 3.5 +/- 2.4 micrograms L-1) at T4. Lipase concentrations showed a similar
      course in both groups. None of the patients showed clinical signs of
      pancreatitis. CONCLUSIONS: Controlled hypotension during surgery was associated
      with a small but significant increase in pancreatitis-associated protein compared
      with controls. The absence of concomitant elevation in lipase concentrations and
      a lack of clinical evidence of pancreatitis damage suggest that hypotension
      induces mild pancreatic stress.

PMID- 12200954
TI  - Morbidity in electroconvulsive therapy.

PMID- 12200955
TI  - Morbidity in electroconvulsive therapy.

PMID- 12200956
TI  - Accidental injection of intravenous bupivacaine.

PMID- 12200957
TI  - Cigarette smoke and its formaldehyde component inhibit bradykinin-induced calcium
      increase in pig aortic endothelial cells.
AB  - Bradykinin-induced increase in the intracellular concentration of free calcium
      evokes an activation of the endothelial nitric oxide synthase (eNOS) enzyme,
      producing nitric oxide (NO). Cigarette smoke inhibits the eNOS-NO-cGMP signaling
      pathway. The pathomechanism of this deleterious effect of smoke on NO production
      is unknown. The aim of this study was to investigate the effect of gas phase
      smoke trapped in a buffer (smoke buffer, SB) on the bradykinin-induced calcium
      increase in cultured endothelial cells. FURA-2-AM was used to detect bradykinin
      induced calcium increase. A sensitive, fluorescent method using O
      phthaldialdehyde was used for the determination of intracellular reduced
      glutathione (GSH) and protein-thiol levels. SB caused a time- and concentration
      dependent inhibition of bradykinin-induced calcium increase. Formaldehyde, a
      component of SB, inhibited bradykinin-induced calcium increase in concentrations
      characteristic for SB. SB decreased both the intracellular GSH (0.22 +/- 0.06 vs.
      2.23 +/- 0.32 mumol/g protein, SB vs. control, p < .001) and protein-thiol levels
      (4.98 +/- 0.54 vs. 7.31 +/- 0.97 microEqu GSH/g protein, SB vs. control, p < .05)
      in the endothelial cells. Intracellular GSH and protein-thiol levels were not
      changed by 80 microM formaldehyde. GSH (4 mM) prevented the effect of SB (p <
      .001) and formaldehyde (p < .05) on the bradykinin-induced calcium increase. Our
      data support the premise that SB inhibits bradykinin-induced calcium increase.
      This inhibition is partially due to protein-thiol oxidation but may also be
      caused by the formaldehyde content of SB, which inhibits calcium increase in a
      protein-thiol-independent manner.

PMID- 12200958
TI  - pH-dependent oxidant production following inhibition of the mitochondrial
      electron transport chain in pulmonary endothelial cells.
AB  - We investigated the effect of changes in intracellular pH (pHi) and Na/H antiport
      activity on intracellular oxidant production in human pulmonary artery
      endothelial cells (HPAEC) following disruption of cellular metabolism. Oxidant
      production was measured with oxidant-sensitive probes (2',7'-dichlorofluorescein
      diacetate [H2DCF], dihydroethidium [DHE]) following treatment with inhibitors of
      mitochondrial electron transport and glycolysis (antimycin/2-deoxyglucose, A/D).
      A/D treatment increased oxidant production in a dose-dependent fashion over 2
      hours. Omission of 2-deoxyglucose did not alter the magnitude of oxidant
      production. Inhibition at more proximal sites in the mitochondrial electron
      transport chain inhibited oxidant production. These data suggested that the
      mitochondrial electron transport chain was the source of oxidant production.
      Fluorescent imaging experiments confirmed the mitochondrial origin of the
      increased oxidant production under these conditions. Maneuvers that reduced pHi
      and inhibited Na/H exchange (acidosis, specific Na/H exchange inhibitors)
      attenuated oxidant production, whereas maneuvers that raised pHi (monensin)
      potentiated oxidant production. The results with the pH-insensitive probe (DHE)
      confirmed that oxidant production was pH-dependent. Oxidant production preceded
      significant loss of cell viability at 6 h following A/D treatment. These results
      demonstrate that oxidant production following inhibition of mitochondrial
      electron transport in HPAEC is pH-dependent and may contribute to endothelial
      cell injury by increasing endogenous oxidative stress.

PMID- 12200959
TI  - Vessel co-option: how tumors obtain blood supply in the absence of sprouting
      angiogenesis.
AB  - The hypothesis that solid tumors are dependent on angiogenesis, the formation of
      new vessels, for outgrowth and metastasis has acquired a central position in
      cancer research and has since inspired many scientists for several decades. Among
      the various angiogenic stimuli that are secreted by tumor cells, members of the
      Vascular Endothelial Growth Factor (VEGF) family are most prominent. More
      recently it has become clear, however, that tumors may use alternative ways to
      obtain blood supply. Vessel co-option, the use of pre-existent vessels, was
      described first in the brain, one of the most densely vascularized organs in the
      body. Thus, brain tumors may develop without the need of an angiogenic switch to
      occur. Obviously, this way of blood supply will not be affected by angiogenesis
      inhibition. In addition, it is predicted that tumors with this type of behavior
      will be less visible in contrast-enhanced MRI. In this article we present our
      recently developed mouse brain model of vessel co-option in melanoma. The effects
      of expression of VEGF on tumor vascularity, and on MRI visualization of these
      brain lesions are described. Possible consequences of anti-angiogenesis therapy
      are discussed.

PMID- 12200960
TI  - Mechanisms of endothelial survival under shear stress.
AB  - Endothelial cells (ECs) are exposed to cytotoxic reactive oxygen species and
      oxidation products of NO, yet they are characterized by low apoptotic rates and
      have an average life span of many years. EC exposure to flow has been shown to
      downregulate cell cycle-related genes and cause cytoskeletal rearrangement. We
      hypothesized that exposure to flow also causes molecular and physiological
      changes that induce antioxidant properties in ECs. We used cDNA array expression
      profiling and protein analysis to study the responses of human ECs exposed to
      flow in a hollow fiber apparatus or the same ECs grown under static conditions.
      Our results show that shear-induced synchronized expression of processes control
      oxidant production; these changes included upregulation of NADH-producing enzymes
      (Krebs cycle dehydrogenases and glyceraldehyde-3-phosphate dehydrogenase [GAPDH])
      accompanied by simultaneous decrease in NADH-depleting pathways (e.g., lactate
      dehydrogenase [LDH]) and diminished production of lactate. Exposure to flow
      upregulated cytoskeletal genes. Our results suggest that, in addition to
      inhibition of cell cycle, exposure to flow influences ECs by controlling
      expression of enzymes involved in the generation of antioxidant intermediates and
      in adaptive control of cell shape. These changes may explain longevity and
      antioxidant efficiency of ECs and may provide insight in mechanisms leading to
      pathological conditions such as arteriosclerosis.

PMID- 12200961
TI  - Mesothelial cells in suspension expose an enriched integrin repertoire capable of
      capturing soluble fibronectin and laminin.
AB  - Pleural cavities are lined by a polarized monolayer of mesothelial cells (MC).
      During pleuritis, MC are shed into effusions, and pleural obstruction may occur.
      Integrins are cell surface receptors mediating interactions with extracellular
      matrix (ECM) proteins. The distribution of beta 1-, beta 3-, beta 4-integrins and
      fibronectin and laminin in normal and chronically inflamed pleura and in/on MC
      from pleural effusions was examined by immunomorphology and flow cytometry.
      Adhesion assays of MC to fibronectin and laminin were performed. In situ, resting
      MC expressed beta 1-, beta 3-, and beta 4-, and alpha v-subunits. Activated MC
      were beta 1- and alpha v-positive and also expressed alpha 3 and alpha 6; beta 4
      was confined to the basal surface of MC; beta 3 was absent. Floating MC from
      effusions neoexpressed alpha 5 and reexpressed beta 3. In vitro, MC surface
      expressed beta 1, beta 3, alpha 3, alpha 5, alpha 6, alpha v, and also alpha 1
      and alpha 2. In normal pleura, fibronectin and laminin were components of the
      basement membrane. In pleuritis, the basement membrane was desintegrated.
      Instead, newly formed fibronectin/laminin containing fibrils extended into the
      submesothelial connective tissue. Floating MC freshly isolated from effusions
      carried fibronectin and laminin on their surface and showed specific binding to
      these ECM proteins. Binding was blocked by anti-beta 1 or anti-alpha 5 and anti
      alpha 6 antibodies, respectively. MC incubated with fibronectin showed a clear
      shift to the S phase, while laminin had no effect. In conclusion, activated and
      detached MC progressively enrich their integrin repertoire. By capturing soluble
      fibronectin and laminin and by matrix-mediated bridging, readhering MC may
      contribute to pleural obstruction. Further, soluble fibronectin bound to alpha 5
      beta 1 might be life-sustaining for floating MC by driving cells into cell cycle.

PMID- 12200962
TI  - Characterization of a human import component of the mitochondrial outer membrane,
      TOMM70A.
AB  - Functional mitochondria require up to 1000 proteins to function properly, with
      99% synthesized as precursors in the cytoplasm and transported into the
      mitochondria with the aid of cytosolic chaperones and mitochondrial translocators
      (import components). Proteins to be imported are chaperoned to the mitochondria
      by the cytosolic heat shock protein (cHSP70) and are immediately pursued by
      Translocators of the Outer Membrane (TOMs), followed by transient interactions of
      the unfolded proteins with Translocators of the Inner Membrane (TIMs). In the
      present study, we describe a human gene, TOMM70A, orthologous to the yeast Tom70
      import component. TOMM70A is ubiquitously expressed in human tissues, maps on
      chromosome 3q13.1-q13.2 and consists of 12 coding exons spanning over 37 kb.
      TOMM70A localizes in the mitochondria of COS-7 cells, and in organello import
      assays confirmed its presence in the Outer Mitochondrial membrane (OM) of rat
      liver mitochondria. TOMM70A could play a significant role in the import of
      nuclear-encoded mitochondrial proteins with internal targeting sites such as
      ADP/ATP carriers and the uncoupling proteins.

PMID- 12200963
TI  - Maintenance of the epithelial barrier in a bronchial epithelial cell line is
      dependent on functional E-cadherin local to the tight junctions.
AB  - Tight junctions (TJ) are essential components of polarized epithelia, and E
      cadherin is important for their formation and maintenance. The bronchial
      epithelial cell line, 16HBE14o-expresses E- and P-cadherin, but not N-cadherin. E
      and P-cadherin levels changed during culture, the former increasing after
      confluence, and the latter were markedly reduced. All detectable E-cadherin was
      bound to beta- and gamma-catenins. We investigated involvement of E-cadherin with
      epithelial integrity using an E-cadherin specific, function-blocking antibody,
      SHE78-7. Surprisingly, apical SHE78-7 exposure caused a prompt fall in
      transepithelial resistance (TER), while TER remained unchanged for 8 hrs after
      basal exposure then dropped. SHE78-7 exposure increased epithelial permeability
      to mannitol, inulin, and 9.5 kDa and 77 kDa dextrans and caused fragmentation and
      loss of the tight junction protein, ZO-1, from the cell borders in some areas.
      Ultrastructural studies showed that all junctional intercellular contact was lost
      in the center of SHE78-7 induced lesions. Near the lesion periphery, epithelial
      structure was maintained, but TJs were dysfunctional as shown by ruthenium red
      penetration. Analysis of epithelial penetration by SHE78-7 revealed discrete,
      local defects in the apical barrier at the top of some cell hills that permitted
      rapid access of the antibody to E-cadherin near the apical surface. In contrast,
      after basal exposure, antibody initially engaged with E-cadherin nearer the basal
      surface and only accessed apical E-cadherin later. Taken together with the TER
      measurements, these data suggest compartmentalization of E-cadherin function
      within 16HBE14o-cells, with only the apical E-cadherin adjacent to the tight
      junctions contributing to the function of the latter.

PMID- 12200964
TI  - Candida albicans and Saccharomyces cerevisiae expressing ALA1/ALS5 adhere to
      accessible threonine, serine, or alanine patches.
AB  - Saccharomyces cerevisiae transformed with Candida albicans ALA1/ALS5 exhibits
      adherence properties similar to C. albicans. Adherence of the fungi to
      immobilized proteins involves hydrogen bonds, is stable to shear forces, and is
      resistant to competition from various biological molecules. The specificity
      determinants of target recognition in Ala1/Als5p-mediated adherence are not
      known. To determine features of target recognition, proteins and small peptides
      were covalently coupled at the N-terminus to the surface of carboxylate-modified
      magnetic beads. C. albicans yeast cells, germ tubes and pseudohyphae and S.
      cerevisiae expressing the adhesin, Ala1/Als5p, adhered to beads coated with
      fibronectin, laminin, type IV collagen, bovine serum albumin, and casein. No
      adherence to beads was observed if a single amino acid was coupled to the beads.
      However, 10-mer homopolymers of threonine, serine, and alanine served as ligands
      for adherence. The presence of a minimum of four contiguous threonine residues in
      a peptide was required for maximal adherence. Coupling of 10-mer peptides from
      fibronectin and Ala1/Als5p each possessing 5-7 threonine or serine residues also
      initiated adherence. On the other hand, a collagen and a fibronectin 10-mer
      peptide with few threonine and serine residues and lysine at the C-terminus did
      not serve as adherence ligands. Both of them are converted to adherence ligands
      by adding threonine or serine residues at the C-terminus or removing the lysine
      residue and adding threonine residues anywhere in the peptide. The presence of
      lysine at the C-terminus may have resulted in coupling of the peptides at both
      the N- and C-termini, thus making the threonine residues inaccessible for
      adherence. Thus, Ala1/Als5p recognizes patches of certain amino acids, which must
      be accessible before adherence will occur.

PMID- 12200965
TI  - Mechanical characterization of bovine periodontal ligament.
AB  - This study is part of a research program that aims to develop a constitutive
      three-dimensional model of the periodontal ligament (PDL) through the
      identification of pertinent material parameters. As part of this program, bovine
      PDL was utilized to establish stress-strain responses under tensile and
      compressive loading conditions. Fresh bovine molars were secured, frozen and
      prepared to appropriate dimensional specifications. Bar-shaped specimens that
      comprised portions of dentine, PDL and bone were produced. Push-pull tests were
      conducted using a specifically constructed loading machine. Full range monotonic
      stress-strain diagrams were generated. The effect of a rate increase on cyclic S
      E diagrams was also determined. The influence of specimen thickness was expressed
      in terms of modulus of elasticity, strength, uniaxial maximizer strain, and
      strain energy density. The overall load-response was heavily hysteretic in
      compression. On the tensile side, after a steep rise, the curve tended to flatten
      out asymptotically. Variations in rate that spanned four orders of magnitude had
      no effect on reciprocal load responses. The E-modulus was in the 4-8 MPa range,
      the strength of the PDL was 1-2 MPa, the maximizer strain was at 45-60% and the
      strain energy density ranged between 0.3 and 0.4 MPa.

PMID- 12200966
TI  - Effect of periodontal treatment on the activity of chitinase in whole saliva of
      periodontitis patients.
AB  - Human salivary chitinase could play a role in the defence against chitin
      containing oral pathogens. The activity levels of chitinase in the whole saliva
      of periodontitis patients were significantly higher than those in saliva from
      controls. Periodontal treatment for a period of 5-6 months resulted in a three-
      to fourfold decrease in this enzyme activity. The activity of beta-N
      acetylhexosaminidase, which is another enzyme that hydrolyses glycosidic
      linkages, also decreased as a result of treatment, although to a lesser extent.
      The decrease in chitinase activity upon treatment of the disease did not
      correlate with the decrease that was seen in clinical attachment loss and
      bleeding on probing, and only a weak correlation was observed with the changes in
      probing pocket depth and plaque index. No correlations were found between the
      above clinical parameters and the decrease in beta-N-acetylhexosaminidase
      activity.

PMID- 12200967
TI  - Quantitative comparison of the cytocidal effect of seven macrolide antibiotics on
      human periodontal ligament fibroblasts.
AB  - The cytocidal effect of seven macrolide antibiotics on human periodontal ligament
      fibroblasts (Pel cells) was studied. Pel cells were exposed for 48 h to
      erythromycin (EM), clarithromycin (CAM), roxithromycin (RXM), azithromycin (AZM),
      josamycin (JM), midecamycin (MDM), and rokitamycin (RKM), and allowed to form
      colonies. The cytocidal effect of the macrolides was measured as a decrease in
      colony-forming efficiency and was found to increase with the concentration. To
      obtain a quantitative measure of the cytocidal effect, the LD50, i.e. the
      concentration that decreases colony-forming efficiency 50% relative to control
      cells, was extrapolated from the concentration-response curves. The rank of the
      macrolides according to their cytocidal effect (LD50) was RKM > RXM > CAM > AZM >
      JM > MDM approximately EM. RKM, RXM, CAM, AZM, and JM were at least 1.7-12.2
      times more cytocidal than MDM or EM. When extrapolated from the concentration
      response curves, the relative survival of the Pel cells exposed to each of the
      macrolides at the MIC90 concentrations for periodontopathic bacteria was
      estimated to be: > or = 53.8% for RKM, > or = 92.7% for RXM, > or = 94.6% for
      CAM, > or = 97.1% for AZM, and > or = 86.2% for EM. The effect of the antibiotics
      on the mRNA expression of alkaline phosphatase (ALP) and type I procollagen (COL)
      was examined in Pel cells exposed for 48 h to RXM, CAM, AZM, and EM, which
      exhibited strong, moderate, and weak cytocidal activity. The constitutive levels
      of both ALP and COL mRNA were retained in cells exposed to RXM at < or = 3
      microM, CAM at < or = 10 microM, and AZM or EM at < or = 3 microM. The MIC90
      against periodontopathic bacteria is < or = 4.8 microM for RXM, 5.3 microM for
      CAM, 2.7 microM for AZM, and 21.8 microM for EM. These results suggest that
      topical administration of CAM or AZM to the gingival crevice at their MIC90
      concentration for periodontopathic bacteria would have little adverse effect on
      the growth and differentiation of the periodontal ligament. It is important to
      note, however, that these findings have yet to be extrapolated to in vivo
      conditions.

PMID- 12200968
TI  - Anti-TGF-beta antibody blocks enamel matrix derivative-induced upregulation of
      p21WAF1/cip1 and prevents its inhibition of human oral epithelial cell
      proliferation.
AB  - We have previously demonstrated that porcine enamel matrix derivative (EMD)
      contains TGF-beta 1 (or a TGF-beta-like substance), and that EMD rapidly
      translocates smad2, which is an effector of the TGF-beta signaling pathway, into
      the nucleus and modulates the proliferation of both human gingival fibroblastic
      and oral epithelial cells in a cell type-specific manner. To investigate the
      involvement of TGF-beta in the growth modulatory action of EMD, two approaches
      have been used in the present study: i) a neutralizing anti-TGF-beta antibody to
      block EMD action, and ii) authentic porcine TGF-beta 1 to compare with EMD. Both
      in epithelial and fibroblastic cells, TGF-beta 1 closely mimicked EMD in nuclear
      accumulation of smad2, phosphorylation of MAP kinase family members, and
      consequent cell type-specific growth modulation. Anti-TGF-beta antibody, at
      levels which completely blocked TGF-beta 1-induced smad2 translocation, strongly
      blocked EMD-induced smad2 translocation. This antibody also blocked other actions
      of EMD in epithelial cells, i.e. p38-MAP kinase (p38-K) phosphorylation,
      p21WAF1/cip1 expression, and inhibition of DNA synthesis. In support of our
      previous proposal, these data suggest that TGF-beta 1 (or a TGF-beta-like
      substance), which is delivered as a principal bioactive factor in EMD, inhibits
      epithelial cell proliferation probably by a smad2-mediated, p21WAF1/cip1
      dependent mechanism. However, the same neutralizing antibody failed to
      convincingly block EMD-induced fibroblastic proliferation, which suggests that
      EMD may contain additional unidentified mitogenic factor(s), which act in
      combination with TGF-beta to fully stimulate fibroblastic proliferation.

PMID- 12200969
TI  - Relationship between vitamin D receptor gene polymorphism and periodontitis.
AB  - Recent studies have shown that vitamin D receptor (VDR) gene polymorphism had
      regulatory effects on bone mineral density (BMD) and bone turnover. The VDR gene
      has also been indicated as a candidate gene for the susceptibility of
      osteoporosis. However, it is unclear whether VDR genotypes could be associated
      with alveolar bone loss of patients with periodontitis, or whether vitamin D
      receptor gene could be a candidate gene for susceptibility to periodontitis. The
      purpose of this study was to answer these two questions. METHODS: Twenty-four
      cases of adult periodontitis (AP), 37 cases of early onset periodontitis (EOP)
      and 39 healthy controls were recruited for the study. Individual samples of
      venous blood and DNA were obtained from each subject. Genotypes of the TaqI VDR
      gene were determined by PCR and TaqI restriction endonuclease digestion. RESULTS:
      One out of 24 AP patients, nine out of 37 EOP patients and two out of 39 healthy
      controls were detected with Tt genotype, while the rest had the TT genotype. The
      detected frequency of Tt genotype was significantly higher in EOP patients
      (24.3%) than in AP patients (4.2%) and healthy controls (5.1%). The frequency of
      t allele was also significantly higher in EOP patients. There was no statistical
      difference in the distribution of TaqI VDR genotypes between AP patients and
      healthy controls. The study suggests that Tt genotype might be a risk indicator
      for the susceptibility to EOP. Carriage of the allele (t) of the TaqI VDR gene
      may increase the risk of developing EOP.

PMID- 12200970
TI  - Cytolethal distending toxin of Actinobacillus actinomycetemcomitans. Occurrence
      and association with periodontal disease.
AB  - The cytolethal distending toxin (Cdt) of Actinobacillus actinomycetemcomitans, a
      periodontal pathogen, is a newly described cytotoxin with immunosuppressive
      properties, capable of causing cell cycle arrest of lymphocytes. The objectives
      of this study were to investigate the occurrence of A. actinomycetemcomitans with
      the cdt genotype in the subgingival plaque of periodontitis patients and to
      determine the association of this bacterial genotype with periodontal disease. A
      total of 146 subgingival plaque samples from periodontitis patients were assayed
      by the PCR method using oligonucleotide primers targeting the cdt operon of A.
      actinomycetemcomitans. Primers targeting the leukotoxin gene A (ltxA) of A.
      actinomycetemcomitans was used to determine the occurrence of the bacteria in the
      plaque samples at baseline. At baseline, A. actinomycetemcomitans was detected in
      106 out of 146 (73%) diseased sites studied. Among the 106 diseased sites found
      to harbor A. actinomycetemcomitans, 13 sites were positive for the bacteria with
      the cdt genotype (12%). Out of the 13 positive sites, 10 sites were obtained from
      patients diagnosed with aggressive periodontitis (77%). Thus, A.
      actinomycetemcomitans with the cdt genetic subtype has low occurrence in the
      subgingival plaque of periodontitis patients. However, a strong association was
      observed between the presence of the bacteria and aggressive forms of
      periodontitis. Thus, the cytotoxic and immunosuppressive properties of A.
      actinomycetemcomitans Cdt may function to cripple the host immunity and
      contribute to the pathogenesis of aggressive periodontitis.

PMID- 12200971
TI  - Cytokine regulation of syndecan-1 and -2 gene expression in human periodontal
      fibroblasts and osteoblasts.
AB  - Cell-surface proteoglycans participate in several biological functions including
      interactions with a variety of growth factors and cytokines. Regulation of
      syndecan-1 and -2 gene expression was investigated in human periodontal ligament
      fibroblasts (PDLF), osteoblasts (OB) and gingival fibroblasts (GF), in response
      to platelet-derived growth factor (PDGF-BB), transforming growth factor (TGF-beta
      1), and interleukin (IL-1 beta) by Northern blot analyses. We also compared the
      effect of PDGF-BB and TGF-beta 1, separately and in combination, in the prolonged
      presence of IL-1 beta on the expression of both syndecan genes. The results
      demonstrated that the three cell lines regulated the expression of syndecan-1 and
      -2 in response to growth factors and cytokines in different manners. These cell
      lines increased syndecan-1 mRNA levels in response to either PDGF-BB or TGF-beta
      1 and decreased levels in response to IL-1 beta. The effect of IL-1 beta on
      syndecan-1 mRNA synthesis was partially reversed after adding PDGF-BB and TGF
      beta 1, separately or in combination, in the presence of IL-1 beta. In contrast,
      syndecan-2 mRNA level was markedly upregulated in response to either TGF-beta 1
      or IL-1 beta in OB when compared with the other two cell lines. However, the
      stimulatory effect of TGF-beta 1 on syndecan-2 mRNA production in OB was
      abolished in the prolonged presence of IL-1 beta. These findings lend support to
      the notion that syndecan-1 and syndecan-2 have distinct functions which correlate
      with their source and functions within the periodontium.

PMID- 12200972
TI  - Mechanisms of cytotoxicity of nicotine in human periodontal ligament fibroblast
      cultures in vitro.
AB  - The use of tobacco products significantly contributes to the progression of
      periodontal disease and poor response to healing following periodontal therapy.
      The purpose of this study was to determine the effects of nicotine, a major
      component of cigarette smoking, on human periodontal ligament fibroblast (PDLF)
      growth, proliferation, and protein synthesis to elucidate its role in periodontal
      destruction associated with its use. Human PDLFs were derived from three healthy
      individuals undergoing extraction for orthodontic reasons. At a concentration
      higher than 2.5 mM, nicotine was found to be cytotoxic to human PDLFs (P < 0.05).
      Nicotine also significantly inhibited cell proliferation and decreased protein
      synthesis in a dose-dependent manner. At concentrations of 50 and 200 microM,
      nicotine suppressed the growth of PDLFs by 48% and 86% (P < 0.05), respectively.
      A 10-mM concentration level of nicotine significantly inhibited the protein
      synthesis to only 44% of these in the untreated control (P < 0.05). Furthermore,
      the effects of antioxidants (superoxide dismutase (SOD); catalase and 2
      oxothiazolidine-4-carboxylic acid (OTZ) and buthionine sulfoximine (BSO) were
      added to search for the possible mechanism of action, as well as a method for the
      prevention, of cigarette smoking-associated periodontal diseases. The addition of
      OTZ, a precursor of cysteine that metabolically promotes GSH synthesis, acted as
      a protective effect on the nicotine-induced cytotoxicity. However, SOD and
      catalase did not decrease the nicotine-induced cytotoxicity. In contrast, the
      addition of BSO, a cellular GSH synthesis inhibitor, enhanced the nicotine
      induced cytotoxicity. These results indicate that thiol depletion could be the
      mechanism for nicotine cytotoxicity. The levels of nicotine tested inhibited cell
      growth, proliferation, and protein synthesis on human PDLFs. This suggests that
      nicotine itself might augment the destruction of periodontium associated with
      cigarette smoking. In addition, these inhibitory effects were associated with
      intracellular thiol levels. Factors that induce glutathione synthesis of human
      PDLF may be used for further chemoprevention of cigarette smoking-related
      periodontal diseases.

PMID- 12200973
TI  - Alterations of neutrophil f-actin kinetics by tobacco smoke: implications for
      periodontal diseases.
AB  - Tobacco smoking is a major risk factor in the incidence and severity of
      periodontal diseases. Alterations of neutrophil function by short-term high
      levels of smoke during the act of smoking (acute smoke exposure) as well as long
      term exposure to lower levels of tobacco substances in the bloodstream (chronic
      smoke exposure) may play a role in the pathogenesis of periodontal diseases in
      smokers. The polymerization and depolymerization of f-actin in response to
      infectious agents or inflammatory mediators is a critical process in a variety of
      neutrophil functions. In this study, we examined the effects of in vitro smoke
      exposure on neutrophils from smokers and non-smokers (which may be comparable to
      in vivo acute smoke exposure) and neutrophils from smokers not exposed to further
      in vitro smoke (which may be comparable to chronic smoke exposure) on f-actin
      kinetics. Peripheral neutrophils were isolated from seven healthy smoking
      subjects and seven healthy age-matched non-smoking subjects and exposed to 1-5
      min of acute smoke in a smoke box system or not exposed to further smoke
      (baseline controls). Selected aliquots of neutrophils from control and 5-min
      exposures of acute smoke were then stimulated with the chemotactic peptide F-met
      leu-phe at 10(-7) M for an additional 30-360 s. Cells were fixed and
      permeabilized, stained for f-actin with NBD phallacidin, and analyzed by flow
      cytometry. From baseline to 5 min of in vitro smoke exposure, there was a 38%
      decline in f-actin stain in non-smokers and a 30% decline in f-actin stain in
      smokers (p > 0.05) with f-actin values slightly higher in smokers than-non
      smokers (p > 0.05). With F-met-leu-phe stimulation, both smokers and-non-smokers
      demonstrated a characteristic rise in f-actin stain from 0 to 120 s with a
      subsequent decline to baseline at 360 s and no significant differences in f-actin
      levels at any time of stimulation between groups. After preincubation with 5 min
      of in vitro smoke, the magnitude of rise in f-actin was less in both smokers and
      non-smokers when compared to cells not incubated with 5 min of smoke (p < 0.05 at
      120 s for both smokers and non-smokers). F-actin values in smokers were higher
      than-non-smokers from 30 to 360 s of F-met-leu-phe exposure (p > 0.05). These
      results demonstrate that in vitro smoke exposure may impair normal f-actin
      kinetics. These alterations in f-actin kinetics may in turn affect other
      neutrophil functions which may impact on the pathogenesis of periodontal diseases
      in smokers.

PMID- 12200974
TI  - Differential expression and distribution of syndecan-1 and -2 in periodontal
      wound healing of the rat.
AB  - Cell-surface proteoglycans participate in several biological functions including
      interactions with adhesion molecules, growth factors and a variety of other
      effector molecules. Accordingly, these molecules play a central role in various
      aspects of cell-cell and cell-matrix interactions. To investigate the expression
      and distribution of the cell surface proteoglycans, syndecan-1 and -2, during
      periodontal wound healing, immunohistochemical analyses were carried out using
      monoclonal antibodies against syndecan-1, or -2 core proteins. Both syndecan-1
      and -2 were expressed and distributed differentially at various stages of early
      inflammatory cell infiltration, granulation tissue formation, and tissue
      remodeling in periodontal wound healing. Expression of syndecan-1 was noted in
      inflammatory cells within and around the fibrin clots during the earliest stages
      of inflammatory cells infiltration. During granulation tissue formation it was
      noted in fibroblast-like cells and newly formed blood vessels. Syndecan-1 was not
      seen in newly formed bone or cementum matrix at any of the time periods studied.
      Syndecan-1 expression was generally less during the late stages of wound healing
      but was markedly expressed in cells that were close to the repairing junctional
      epithelium. In contrast, syndecan-2 expression and distribution was not evident
      at the early stages of inflammatory cell infiltration. During the formation of
      granulation tissue and subsequent tissue remodeling, syndecan-2 was expressed
      extracellularly in the newly formed fibrils which were oriented toward the root
      surface. Syndecan-2 was found to be significantly expressed on cells that were
      close to the root surface and within the matrix of repaired cementum covering
      root dentin as well as at the alveolar bone edge. These findings indicate that
      syndecan-1 and -2 may have distinctive functions during wound healing of the
      periodontium. The appearance of syndecan-1 may involve both cell-cell and cell
      matrix interactions, while syndecan-2 showed a predilection to associate with
      cell-matrix interactions during hard tissue formation.

PMID- 12200975
TI  - Platelet-rich plasma and bovine porous bone mineral combined with guided tissue
      regeneration in the treatment of intrabony defects in humans.
AB  - BACKGROUND: A combination of platelet-rich plasma (PRP), bovine porous bone
      mineral (BPBM) and guided tissue regeneration (GTR) has been shown to be
      effective in promoting clinical signs of periodontal regeneration in intrabony
      defects. As an initial attempt to clarify the role played by each of the three
      treatment components, this study was performed to compare the clinical
      effectiveness of two regenerative techniques for intrabony defects in humans: a
      combination of PRP/BPBM/GTR vs. GTR. MATERIAL AND METHODS: Eighteen patients
      participated in the study. Using a split-mouth design, interproximal bony defects
      were surgically treated with either an absorbable membrane made of polylactic
      acid for GTR or a combination of PRP/BPBM/GTR. Changes in pocket depth,
      attachment level and defect fill as revealed by 6-month reentry surgeries were
      evaluated. RESULTS: Both treatment modalities resulted in significant pocket
      depth reduction and clinical attachment gain as compared to baseline values.
      Pocket depth reduction was 4.98 +/- 0.96 mm on buccal and 4.93 +/- 0.92 mm on
      lingual sites of the PRP/BPBM/GTR group and 3.62 +/- 0.81 mm on buccal and 3.54
      +/- 0.88 mm on lingual sites of the GTR group. The gain in clinical attachment
      observed was 4.37 +/- 1.31 mm on buccal and 4.28 +/- 1.33 mm on lingual sites of
      the PRP/BPBM/GTR group and 2.62 +/- 1.23 mm on buccal and 2.44 +/- 1.21 mm on
      lingual sites of the GTR group. The amount of defect fill observed was 4.78 +/-
      1.26 mm on buccal and 4.66 +/- 1.32 mm on lingual sites of the PRP/BPBM/GTR group
      and 2.31 +/- 0.76 mm on buccal and 2.26 +/- 0.81 mm on lingual sites of the GTR
      group. All differences between the two groups were statistically significant in
      favor of the PRP/BPBM/GTR group. CONCLUSIONS: The results of this study suggest
      that PRP and BPBM provide an added regenerative effect to GTR in promoting the
      clinical resolution of intrabony defects on patients with severe periodontitis.

PMID- 12200976
TI  - Microbiological, immunological and genetic factors in family members with
      periodontitis as a manifestation of systemic disease, associated with
      hematological disorders.
AB  - The microflora, immunological profiles of host defence functions, and human
      leukocyte antigen (HLA) findings are reported for a mother, son and daughter who
      were diagnosed as having 'periodontitis as a manifestation of systemic diseases,
      associated with hematological disorders'. Examinations were made of the bacterial
      flora from the periodontal pocket, neutrophil chemotaxis, neutrophil
      phagocytosis, and the genotypes (DQB1) and serotypes (DR locus) of HLA class II
      antigens. Phenotypic analyses of the peripheral lymphocytes were also conducted.
      The subgingival microflora from the mother was dominated by Gram-negative rods,
      especially Porphyromonas endodontalis, Prevotella intermedia/Prevotella
      nigrescens and Fusobacterium nucleatum. Subgingival microflora samples from the
      son and daughter were dominated by Gram-positive cocci and Gram-positive rods.
      Through the use of polymerase chain reaction, Campylobacter rectus and
      Capnocytophaga gingivalis were detected in all subjects, whereas Porphyromonas
      gingivalis, P. intermedia, and Treponema denticola were not detected in any
      subjects. All three subjects showed a remarkable level of depressed neutrophil
      chemotaxis to N-formyl-methionyl-leucyl-phenylalanine, although their phagocyte
      function levels were normal, in comparison to healthy control subjects. Each
      subject had the same genotype, HLA-DQB1*0601, while the mother had HLA-DR2 and
      HLA-DR8, and the son and daughter had HLA-DR2 only. In summary, the members of
      this family showed a similar predisposition to periodontitis with regard to
      certain host defence functions. It is suggested that the depressed neutrophil
      chemotaxis that was identified here could be a significant risk factor for
      periodontitis in this family.

PMID- 12200977
TI  - Resistance to antimalarials.

PMID- 12200978
TI  - Breastfeeding in Botswana: practices, attitudes, patterns, and the socio-cultural
      factors affecting them.
AB  - A cross-sectional descriptive study was conducted in four randomly selected
      districts of Botswana. Two study sites were chosen in each district. Four hundred
      households with children under 3 years old were enrolled into the study. A
      structured questionnaire was administered to mothers of eligible children in 50
      households in each of the eight sites. About half the families had monthly
      incomes below 400 Pula (1 US$ = 4.6 Pula). The majority of families had only one
      child under 3 years of age. A total of 76.4 per cent of the mothers were single
      and a high proportion of them had primary or secondary education. Over half, 59.3
      per cent, of the mothers had a high level of information about breastfeeding
      mainly obtained before conception; 94.4 per cent of the mothers believed that
      breastfeeding was better than bottlefeeding. Ninety-five per cent of the mothers
      had breastfed their children, and they started breastfeeding immediately or a few
      hours after delivery. More than 85 per cent of the mothers were planning to
      continue breastfeeding for 18 months or more. The majority obtained advice about
      breastfeeding from health workers. The main reason for stopping breastfeeding was
      that the mother was at work or school. Although 58.2 per cent of mothers had
      little or no support for breastfeeding from the community it had a positive
      effect on their decision to breastfeed. The majority of mothers indicated their
      confidence about breastfeeding when they were pregnant. Over three-quarters (79.6
      per cent) of the mothers delivered in government hospitals, and nearly all were
      roomed with their babies after delivery.

PMID- 12200979
TI  - Hematological changes and predictors of bone marrow recovery in patients with
      neutropenic episodes in acute lymphoblastic leukemia.
AB  - A total of 30 episodes of neutropenia in 16 patients of acute lymphoblastic
      leukemia, aged between 1 and 12 years were studied prospectively. In the initial
      treatment phase (induction of remission, consolidation and CNS prophylaxis) 92.8
      per cent episodes were prolonged (> 7 days) and 85.7 per cent of them had
      profound neutropenia (absolute neutrophil counts < 0.200 x 10(9)/l). In contrast,
      in the maintenance phase, only 64.2 per cent were of prolonged duration; of them
      57.1 per cent had profound neutropenia. Most patients in neutropenia of prolonged
      duration had anemia (Hb < 8 g/100 ml) and thrombocytopenia (platelet < 100 x
      10(9)/l). Regularly increasing trends were seen in total leucocyte counts (TLC),
      absolute monocyte counts (AMC) and platelet counts from 4 days prior to recovery
      of absolute neutrophil counts (ANC). Of all the parameters, platelet count (> 100
      x 10(9)/l) and AMC (> 0.1 x 10(9)/l) recovered 4 and 1 days, respectively, prior
      to recovery of ANC above 0.5 x 10(9)/l. Recovery of platelet counts (4 days prior
      to recovery of ANC) and possibly AMC can be considered early predictors of bone
      marrow recovery. These parameters can be used in conjunction with clinical
      condition to decide about early discharge of leukemia patients with neutropenia,
      especially in developing countries where prolonged stay can result in hospital
      acquired infections.

PMID- 12200980
TI  - Reversal of iron deficiency anemia-induced peripheral neuropathy by iron
      treatment in children with iron deficiency anemia.
AB  - The effects of iron deficiency anemia (IDA) on nerve conduction and efficiency of
      iron therapy were investigated by peripheral nerve-electrophysiological
      measurements. Eighteen children (10 boys, eight girls; mean age 31 +/- 1.3
      months) with IDA and 12 healthy children (six boys, six girls; mean age 29 +/-
      1.3 months) were enrolled into the study. Nerve conduction velocity was measured
      in the median and posterior tibial nerve. After nerve conduction values were
      determined in the patients and controls, 6 mg/kg/24 h ferrous sulphate was given
      orally to the patients for 3 months and nerve conduction velocity tests were
      performed again. Median/motor and sensory nerve conduction velocity and
      tibial/motor nerve distal-amplitute values of children with IDA were lower than
      for the control group (p < 0.05, p < 0.01 and p < 0.001 respectively). With iron
      supplementation these values increased to the normal levels and even higher than
      control levels for some parameters. In correlation studies between whole blood
      parameters and nerve conduction velocity results, there was a correlation between
      median/sensory nerve conduction velocity values and serum iron levels.
      Additionally there was a correlation between some nerve conduction velocity
      values and age. In conclusion, the evidence from this preliminary study suggests
      that peripheral neuropathy may develop in children with IDA. Peripheral
      neuropathy symptoms in these patients may be improved by iron therapy.

PMID- 12200981
TI  - Changing spectrum of sporadic acute viral hepatitis in Indian children.
AB  - From August 1997 to January 2000, 172 children (< or = 14 years) with acute viral
      hepatitis were studied. Their clinical features, investigations and outcome were
      noted. Viral markers (IgM anti-HAV, IgM anti-HEV, HBsAg and anti-HCV) were
      measured by ELISA using commercial kits. The mean age of these children was 5.6
      +/- 2.9 (range, 4 months to 14 years) with a male to female ratio of 120:52.
      Prodromal symptoms were present in 161 (94 per cent) and icteric hepatitis was
      diagnosed in 168 (98 per cent) cases. Splenomegaly was noted in 53 (31 per cent),
      ascites in 52 (30 per cent) and encephalopathy (ALF) in 56 (32.6 per cent) cases.
      Sixteen (31 per cent) children with ascites had spontaneous bacterial peritonitis
      (SBP). Fifteen (27 per cent) children with encephalopathy died. Viral markers
      were positive in 166 (96.5 per cent) and they were: A in 111 (64.5 per cent), E
      in 28 (16.3 per cent), B in 13 (7.6 per cent), A + E in 12 (7 per cent), A + E +
      C and A + C in one each. Mortality in acute liver failure was more when
      associated with SBP (100 per cent) than without (20 per cent) (p < 0.001). We
      conclude that HEV is the second most common cause of sporadic acute viral
      hepatitis in children. Atypical presentations, such as splenomegaly, ascites, and
      SBP were present in virtually one-third of cases. In cases of ALF, the presence
      of ascites and SBP depicts a worse outcome.

PMID- 12200982
TI  - Rotavirus strain diversity in Rio de Janeiro, Brazil: characterization of VP4 and
      VP7 genotypes in hospitalized children.
AB  - Rotavirus strains from 91 patients treated at a children's hospital from 1996 to
      1998 in Rio de Janeiro, Brazil, were characterized by electropherotyping, reverse
      transcription-PCR amplification for P and G genotypes, and Southern
      hybridization. Results obtained showed that following predominant [P],G type
      combination: P[4], G2 (21 per cent), P[8], G1 (17 per cent), P[8], G3 (13 per
      cent), which are prevalent throughout the world. However, an unexpected number of
      cases were associated with uncommon genotypes: P[8], G2 (13 per cent), P[8], G5
      (11 per cent), P[8], G9 (7 per cent), P[8], G10 (4 per cent), P[6], G4 (3 per
      cent), P[6], G3 (1 per cent), P[4], G9 (1 per cent), and P[6], G9 (1 per cent).
      Mixed infections with more than one type were identified in only two cases and 16
      per cent of the samples were not G and/or P typeable. A subset of G types was
      confirmed by Southern hybridization and chemiluminescent detection. Rotavirus
      seasonal distribution was observed between April and July. The contribution of
      the results obtained in the present investigation corroborates the required
      epidemiological surveillance for rotavirus infection in Brazil.

PMID- 12200983
TI  - Morphometry of single small enhancing computed tomographic lesions: outcome and
      effect of albendazole therapy.
AB  - Single small enhancing computerized tomographic (CT) lesions (SSECTLs) are common
      in children with focal seizures. However, there is a paucity of systematic
      information regarding their morphometry, effect of albendazole therapy and long
      term outcome. The objectives were to study the pattern of SSECTL on radiological
      follow up, alterations made by albendazole therapy, and correlation with seizure
      recurrence. A randomized, placebo controlled, double blind trial was carried out
      at the Advanced Pediatric Center, PGIMER, an urban tertiary-care teaching
      hospital. Sixty-three children between 2 and 12 years of age with focal seizures
      for < 3 months and SSECTLs were included in the study. All children were randomly
      assigned to receive either albendazole (15 mg/kg/day) or placebo for 28 days. CT
      scan was done at 1 and 3 months after beginning treatment. Codes opened after 6
      months of recruitment in the study showed that 31 had received albendazole and 32
      had received placebo. Over a period of 3 months, natural resolution of SSECTL
      passed through many stages. Albendazole was seen to accelerate this natural
      process as evident by the progression of various morphometric markers. An
      increase in the size of the lesion was associated with early seizure recurrence.

PMID- 12200984
TI  - Cutaneous anthrax: an endemic outbreak in south India.
AB  - Although human anthrax has become rare, endemic outbreaks still occur in tropical
      countries, parts of South America and Europe. We report 23 cases of cutaneous
      anthrax due to an endemic outbreak of animal and human anthrax in South India.
      These patients were admitted to our hospital between July 1998 and July 2001.
      Children outnumbered adults and most of them had lesions on the exposed sites.
      The majority of patients reported the death of infected animals in the
      neighbourhood without any direct contact with dead animals. Hence, vector borne
      transmission was suspected in most of the cases. Diagnosis was confirmed by the
      presence of a typical ulcer with eschar, Gram-stained smears from ulcers and
      epidemiological evidence. Except for one fatal case, all patients responded to
      treatment.

PMID- 12200985
TI  - A comparison of high versus low dose recombinant human erythropoietin versus
      blood transfusion in the management of anaemia of prematurity in a developing
      country.
AB  - The purpose of this study was to evaluate the effectiveness of early treatment
      with erythropoietin (EPO) in two different treatment regimes (high vs. low dose)
      in comparison to the conventional treatment of packed red blood cell (PRBC)
      transfusions in the management of anaemia of prematurity in a country with
      limited resources. An open controlled trial was conducted on 93 preterm infants
      (7 days postnatal age, 900-1500 g birthweight). Patients were randomly assigned
      either to a low dose (250 IU/kg), a high dose (400 IU/kg), or a control group.
      EPO was administered subcutaneously three times a week and all infants received 6
      mg/kg iron orally from study entry to endpoint of therapy. Haematological
      parameters were measured and compared. The success was defined as an absence of
      transfusions and a haematocrit that did not fall below 30 per cent during the
      time period that the infants were in the study. The three groups were
      statistically comparable at study entry with respect to gestational age,
      birthweight, Apgar scores, and haematological values. Over the period that the
      infants were in the study, 75 per cent of the low dose group and 71 per cent of
      the high dose group met the criteria for success compared with 40 per cent in the
      control group (p < 0.001). However, there was no significant difference in the
      number of transfusions when the low and high EPO dose groups (9.5 per cent) were
      combined and compared with the control group (26.7 per cent) p = 0.0587. It was
      concluded that in stable infants, 900-1500 g, where phlebotomy losses are
      minimized and stringent transfusion guidelines are adhered to, EPO does not
      significantly decrease the number of transfusions. A conservative approach in the
      management of anaemia of prematurity, is a viable alternative in areas with
      limited resources.

PMID- 12200986
TI  - Konzo outbreak, in the south-west of the Democratic Republic of Congo, 1996.
AB  - In August 1996, cases of poliomyelitis were reported in Kahemba zone, in the
      south-west of the Democratic Republic (DR) of Congo. The diagnosis was reviewed
      and charged to Konzo, a spastic paraparesis attributed to food cyanide
      intoxication. In order to describe the phenomena, a community-based survey took
      place and found 237 people affected. The highest prevalence was found in the most
      isolated part of the zone. The patients suffered from an isolated non-progressive
      spastic paraparesis of abrupt onset. Children and women were the most affected
      groups, especially women after childbirth. Most of the patients developed the
      disease after 1990 with 101 cases in 1996. Cassava processing was the same over
      time and in all the villages. The study did not fully explain the increased
      number of cases in 1996 but suggested that complementary investigations regarding
      micronutrient intakes, especially vitamin A, would be necessary.

PMID- 12200987
TI  - Changing profile of retinopathy of prematurity.
AB  - The aim of this study was to determine the evolving trends of retinopathy of
      prematurity (ROP) at a tertiary neonatal intensive care unit. In an ongoing
      screening programme for ROP, we estimated the incidence of ROP among at-risk
      neonates in a tertiary care unit. We compared our data over the last 12 months
      (1999-2000; period II) to the previously published data (1993-94; period I) to
      study changes in the spectrum of the disease. The overall incidence of ROP in
      period II was not significantly different from the incidence in period I (32 vs.
      20 per cent, p > 0.05). However, a decreasing trend in the proportion of severe
      ROP (stage III) from 46 to 21 per cent in the later period was noted. The need
      for cryotherapy also dropped significantly compared with the earlier period (8
      vs. 46 per cent respectively, p < 0.05). On multivariate analysis, apnea (p <
      0.001; RR = 12.5; 95 per cent CI, 3.03-50.9; clinical sepsis (p < 0.001; RR =
      5.7; 95 per cent CI, 1.6-20.7); and male sex (p < 0.001; RR = 6.3; 95 per cent CI
      1.6-25.5) emerged as significant risk factors. Although the incidence of ROP is
      static, the more severe form of the disease (stage III) is showing a decline. Our
      data suggests that efficient management of apnea and sepsis may be crucial in
      further minimizing the risk of ROP.

PMID- 12200988
TI  - Sizes at birth in Shiraz, Iran.
AB  - Size at birth of a random sample of 507 singleton healthy neonates (244 boys and
      263 girls) of Shiraz (southern Iran) is presented. Mean +/- SD of girls and boys
      (p-value for sex difference) of supine length (mm), weight (g), mid upper arm
      circumference (mm), head circumference (mm) and chest circumference (mm) were
      estimated as 488 +/- 21 and 494 +/- 23 (p < 0.05); 3150 +/- 450 and 3300 +/- 500
      (p < 0.005); 105 +/- 8 and 106 +/- 10 (p < 0.01); 342 +/- 13 and 346 +/- 15 (p <
      0.0001); 324 +/- 18 and 326 +/- 20, (p > 0.05), respectively. Mothers' level of
      education, mothers' weight before conception and prior to giving birth, and
      family social class were identified as factors affecting size at birth, while
      birth order and fathers' level of education showed no significant effects on
      these measurements. Sizes at birth were significantly correlated together (p <
      0.0001). The highest and lowest correlations were observed between chest
      circumference and weight (r = 0.77) and arm circumference and length of neonates
      (r = 0.45), respectively. The representativeness of the data suggest that the
      measurements obtained are likely to be applied to urban population of neonates of
      Iran.

PMID- 12200989
TI  - Major birth defects among infants with Down's syndrome in Alexandria, Egypt (1995
      2000).
AB  - A case-control study of 514 infants with confirmed Down's syndrome (DS) was
      carried out during the period 1 July 1995-30 June 2000 to investigate the risk
      factors for the occurrence of congenital anomalies among DS cases. Our results
      showed that the significant risk factors for developing any type of congenital
      anomalies among DS were: parental consanguinity, grand-maternal consanguinity,
      use of antibiotics, use of oral contraceptive pills, diabetes mellitus, and
      maternal fever. The interaction between trisomy 21 genes and consanguinity and/or
      environmental factors can increase the risk of several additional birth defects.

PMID- 12200990
TI  - Recurrent Streptococcus pneumoniae meningitis.

PMID- 12200991
TI  - A study of the causes of diarrhoea in hospitalized children in Nongoma, KwaZulu
      Natal, South Africa.

PMID- 12200992
TI  - Is there any association of a specific chest X-ray pattern and bacteremia in
      children with penumonia?

PMID- 12200993
TI  - Abscess tonsillectomy for acute peritonsillar abscess.
AB  - Peritonsillar abscess (PTA) is a common but potentially serious complication of
      acute exudative tonsillitis. Several treatment guidelines have been described
      including needle aspiration, incision and drainage or abscess tonsillectomy. From
      January 1996 to September 2000 145 patients (53 female and 92 male, age range 3
      95 years) were treated for PTA at the Department of Otorhinolaryngology, Head and
      Neck Surgery of the MLU Halle-Wittenberg, Germany. The highest incidence of PTA
      was observed in the second and third decades of life. Immediate abscess
      tonsillectomy was performed in 105 cases. This procedure, considered as safe and
      easy, has a lot of advantages. Compared with other treatments, it removes the
      abscess with amelioration of the trismus and dysphagia. Needle aspiration as the
      initial and only treatment was performed in 13 patients. In 20 patients without
      clinical improvement after aspiration, abscess tonsillectomy was undertaken. We
      conclude that immediately performed abscess tonsillectomy is an effective and
      safe treatment for peritonsillar abscess.

PMID- 12200994
TI  - [Transmandibular buccopharyngectomy after radiotherapy for orpharyngeal cancer].
AB  - MATERIALS & METHODS: We present a retrospective study of 95 patients with
      recurrence of oropharyngeal carcinoma after exclusive radiotherapy. The treatment
      consisted in a salvage composite resection in all cases. RESULTS & DISCUSSION:
      Since the use of muscular flaps, the post-operative complications have been
      relatively minimised but the carcinologic results were disappointing: only 20% of
      patients were alive free of disease at 5 years. The main prognostic factors for
      overall survival were the stage rT of the relapse, the histologic invasion of the
      nodes and the quality of the resection. The anatomic site of relapse did not
      influence the survival. CONCLUSION: Our serie confirms the high frequency of
      second primary tumors in oropharyngeal cancers. Rigorous selection of patients
      for exclusive radiotherapy is mandatory to decrease the number of relapses and
      might avoid salvage surgery.

PMID- 12200995
TI  - [Percutaneous gastrostomy for cervicofacial cancer: Bordet Institute experience].
AB  - INTRODUCTION: The establishment of a direct enteral feeding route is critical in
      the overall treatment of many patients with head and neck cancer. This study
      evaluated the indications, success rate, and complications associated with
      endoscopic gastrostomies. MATERIALS & METHODS: 71 endoscopic percutaneous
      gastrostomies were created in 67 patients. The main indication for gastrostomy
      was the need for nutritional support in malignant head and neck tumors. Two
      localizations, buccal cavity and oropharynx, comprised 45% of the cases (32/71).
      RESULTS: All the procedures were successful. The one severe complication
      (peritonitis) required laparotomy. The duration of enteral nutrition via
      gastrostomy varied from two days to more than two years. There were no long-term
      complications. CONCLUSION: The method is simple, cost-saving and is very
      important to prevent malnutrition, the most predictive parameter for the
      occurrence of major postoperative complications.

PMID- 12200996
TI  - [Cervicofacial lymphangioma in adults (10 case reports)].
AB  - INTRODUCTION: Cystic cervico-facial lymphangioma (DDFL) are relatively rare.
      Because of their size and site, they pose a real problem in treatment. The
      authors present a retrospective study about 10 cases. MATERIALS & METHODS: The
      mean age of this series of patients was 31 years, with a slight female
      preponderance. Ultrasound scanning is sufficient to establish the diagnosis. CT
      or MRI scan helps to show whether there is parapharyngeal or mediastinal
      extension. RESULTS: Every patient in this series underwent operation. We had one
      recurrence and two postoperative neurological sequelae. DISCUSSION: Although
      there is little difficulty in the diagnosis of this condition, it is difficult to
      treat because of extension which involve the face, the floor of mouth and tongue
      base, and also the major structures in neck. Current interest is centred on
      treating these lesions with sclerosis agents, either for recurrence or, according
      to some authors, as a first therapeutic option.

PMID- 12200997
TI  - [Medicine yesterday, today and tomorrow].

PMID- 12200998
TI  - [Thyroid surgery (356 cases): risks and complications].
AB  - The purpose of this study was to evaluate the risks and complication rate of
      thyroid surgery. The authors present a retrospective study of 356 patients
      surgically treated for thyroid nodules, between 1987 and 1998, at the military
      hospital of Tunis. The patients were categorised into 3 groups: group I: 238
      solitary thyroid nodules (66.8%); group II: 92 multinodular goitres (25.8%)
      included 12 retrosternal goitres (3.37%) and group III: 26 cases of Basedow's
      disease (7.4%). Patients benefitted from unilateral surgery in 72% of cases and
      from bilateral surgery (total or subtotal thyroidectomy) in the remaining 28% of
      cases. Malignancy was found in 34 cases (9.5%). The complications observed were
      haemorrhage (0.56% of cases), unilateral post operative recurrent laryngeal palsy
      (1.12% of cases), and permanent hypoparathyroidism in 0.81% of cases. Experienced
      surgeons and the use of a meticulous surgical technique can reduce the incidence
      of post operative complications in thyroid surgery.

PMID- 12200999
TI  - [Thyroid papillary microcarcinoma. Salah Azaiz Institute experience].
AB  - The incidence of thyroid papillary microcarcinoma appears to be increasing and
      therapeutic modalities remain controversial. This retrospective study concerns 25
      cases, from 1978 to 1999. The circumstances of diagnosis were: a cervicotomy for
      thyroid nodule (88% of cases), cervical node metastases (8%), and osseous
      metastases (4%). The sensitivity of ultrasounds was 22.2%, that of scintigraphy
      was 9.1% and that of extemporaneous histological examination was 18.2%.
      Multifocality was found in 16% of cases and bilaterality in 16.6%. Treatment
      modalities were guided by histological examination. Adjunctive radioiodine
      ablation was used for 20% of the patients. The treatment of the osseous
      metastases was completed with external irradiation. The average follow up was 4.8
      years (4 months to 19 years), with a rate of survival without disease of 100%.

PMID- 12201000
TI  - Clinical and histopathological correlates of the proliferative activity in
      squamous cell laryngeal carcinoma.
AB  - OBJECTIVES: To elucidate the clinical and histopathological significance of the
      proliferative activity as determined by PCNA and Ki67 levels and mitotic counting
      (MC) in laryngeal squamous cell cancer (LSCC). STUDY DESIGN: An analysis of
      clinical, histopathological and immunhistochemical (PCNA0 and Ki67) results of 28
      patients, who were treated for LSCC, was made. METHODS: Clinical data of the
      patients were reviewed and corresponding archival paraffin embedded tissue
      samples were obtained. Histopathological studies and MC were performed, and PCNA
      and Ki67 positivity was assessed. RESULTS: There was no association between the
      mean values of the proliferative markers, and N stage and T stage of the patients
      as well as laryngeal site of involvement (p > 0.05). There was a correlation
      between the proliferative indicators and tumor grade (p < 0.05). A correlation
      was also encountered between the PCNA, Ki67 and MC values (p = 0.02). CONCLUSION:
      The proliferative markers studied are not reliable indicators for the presumptive
      diagnosis of occult neck metastasis. They may be used as complementary tools to
      the conventional histopathologic grading systems to assess the tumour
      differentiation in LSCC.

PMID- 12201001
TI  - Laryngeal tuberculosis.
AB  - Laryngeal tuberculosis is the most frequent granulomatous disease of the larynx.
      The disease has changed its behaviour with regard to average age of onset site
      and type of lesion. Laryngeal tuberculosis is usually secondary to, or at least
      contemporary with, pulmonary tuberculosis. Other recents studies, however,
      conclude by accepting a frequency of up to 20% for primary laryngeal
      tuberculosis. The age of presentation is between 41-50 years. Among the risk
      factors identified are the consumption of tobacco, alcohol, malnutrition and
      immunodeficiency. The predominant symptom was dysphonia (90%) either in isolation
      or accompanied by odynophagia (45%). Today, the ulcero-infiltrative lesions which
      predominantly affected the posterior larynx are not observed. At the present time
      the macroscopic appearance corresponds to a diffuse oedema or to a pseudo-tumoral
      image located in any zone. Any non-specific chronic laryngitis of poor evolution
      should lead us to suspect a laryngeal tuberculosis.

PMID- 12201002
TI  - Hearing preservation in patients with labyrinthine fistulae.
AB  - INTRODUCTION: Labyrinthine fistula is the most common complication of chronic
      middle ear disease with cholesteatoma. We present a series of cases of
      labyrinthine fistula found during the surgical procedures carried out for
      cholesteatoma in a district hospital setting, over 11-year period. MATERIALS AND
      METHODS: This is retrospective study based on case notes and author's database
      for the period of 1987 to 1999. During this period 382 operations were performed
      and 25 (6.54%) patients found to have labyrinthine fistulae. We looked at the
      incidence, clinical presentation, surgical technique and hearing outcomes. A
      standard fistula classification system has been used in order to compare the pre
      and post-operative hearing. RESULTS: Records were available in 22 cases, which
      were 12 men, and 10 women with mean age of 45.2 years at presentation. Only one
      third had presented with vertigo. Lateral semicircular canal was the most
      affected site (95%). Fistulae classified as types: I = 8 (36.3%), II-a = 1
      (4.5%), II-b = 5 (22.9%) and III = 8 (36.3%). All patients had a standard open
      technique mastoidectomy. In 5 ears the hearing was lost pre-operatively (1 type
      II-b and 4 type III fistulae), and in remaining 17 the bone conduction thresholds
      remained unchanged in 15 (88 per cent) ears. Two dead ears directly related to
      the surgery and both were of type III fistula. CONCLUSIONS: One-staged mastoid
      surgery can be the treatment of choice in these cases. Meticulous surgical
      technique with adequate sealing of the fistula helps to preserve the hearing. An
      appropriate classification system is an essential tool in presentation and
      comparison of results.

PMID- 12201003
TI  - Airbag and hearing loss: our experience.
AB  - The international literature reports sporadic cases of sudden sensorineural
      hearing loss associated with Airbag inflation in subjects involved in car
      accidents, who had never suffered from hearing loss and had no history of
      pathologies that could otherwise explain the hearing loss. The authors have
      studied the actual incidence of this possibility, analysing 25 subjects submitted
      to an airbag inflation. Only subjects who had never suffered from previous
      otological pathology were considered for the study. The examination was carried
      out 3 to 10 days after the accident. Otoscopical examination, tympanometry and
      audiometry were normal in all the examined subjects. The Author's opinion is that
      traumatic hearing loss following airbag inflation is a rare or exceptional
      incident that probably occurs in subjects with a particular susceptibility and
      sensitivity.

PMID- 12201004
TI  - [Adenocarcinoma of the endolymphatic sac in children. A case report].
AB  - We report a case of an adenocarcinoma of the endolymphatic sac in a 13 years old
      child, which was fortuitously discovered at the time of radiological
      investigation of growth delay. Arising from the end of the endolymphatic sac,
      this rare tumour shares a similar clinic expression with other cerebellopontine
      angle pathologies. Radiological investigation reveals a moth eaten appearance to
      the posterior temporal bone and specific bony inclusions. With MRI there is an
      intense and/or intermediate signal on T1, a hyper signal on T2 and T1 enhancement
      with injection of gadolinium. Treatment is surgical and local recurrences are not
      uncommon. After histological confirmation, a search for Von Hippel-Lindau disease
      is mandatory because this tumour is not exceptional among this subset of
      patients. Diagnosis and therapeutic criteria will be highlighted by our case and
      a review of the literature.

PMID- 12201005
TI  - Treating vertigo with vestibular rehabilitation: results in 155 patients.
AB  - Balance is fundamental to our daily activities and the vestibular system,
      together with vision and proprioceptive functions, are the main structures
      involved in this process. Dizziness is the main clinical manifestation of
      malfunction of these systems. The mechanisms of vestibular compensation are one
      of the most studied aspects since they play an important role in the patient's
      everyday activities. In this retrospective description of a series of cases the
      authors present their results in 155 patients that underwent a program of
      vestibular rehabilitation (VR). The program, first described by Cawthorne and
      Coosey, is based on mechanisms of potentiation of the cervico-ocular reflex and
      substitution of the lost vestibular cues for visual and somatosensory cues. The
      results were satisfactory (remission or partial cure) in 75.5% of the patients,
      with an average treatment time of up to 2 months and 5 or fewer sessions
      performed in most of the cases. The results were somewhat inferior in those cases
      in which a central vestibular lesion or more than one etiologic factor was
      present. The results of a subgroup of elderly patients (age > 65 years) were
      similar to those of the total number of studied subjects. Vestibular
      rehabilitation, associated to the specific etiological treatment, appears to be a
      very useful tool in the management of patients suffering from dizziness of all
      ages, although different clinical responses to the therapy may vary according to
      the presence of a central or a peripheral vestibular lesion or multiple
      etiological factors.

PMID- 12201006
TI  - Prognostic value of mandibular involvement in oral cavity cancers.
AB  - OBJECTIVES: The aim of the study was to determine, in a homogeneous population,
      the prognostic impact of mandibular involvement in oral cancers. STUDY DESIGN:
      Retrospective study of 117 patients with T4 squamous cell carcinoma of the oral
      cavity treated by surgery and radiotherapy in the ENT Department of Bichat-Claude
      Bernard Hospital. All patients had histologically confirmed mandibular
      involvement. Patients with partial involvement of the mandible underwent rim
      mandibulectomy (RM) and those with extensive invasion underwent segmental
      mandibulectomy (SM). METHODS: The local failure rate and the overall survival
      curves were calculated with respect to type of mandibulectomy. The causes of
      death were analysed. RESULTS: The surgery was conservative in 55 cases (47%) and
      segmental in 62 patients (53%). The degree of mandibular involvement did not
      influence the local failure rate (29% and 25% in the RM and SM groups,
      respectively). On the other hand, it strongly influenced vital outcome, as five
      year survival was only 25.4% after segmental mandibulectomy, compared to 40%
      after rim mandibulectomy. The metastases and the second primary tumors were more
      frequent in the SM group. CONCLUSION: The degree of mandibular invasion
      influenced the survival rate of patients with squamous cell carcinoma of the oral
      cavity but this difference is not due to local failure.

PMID- 12201007
TI  - Correlation between interdental occlusal plane and plantar arches. An EMG study.
AB  - The Authors carried out an experimental study on a homogeneous group of young
      people to provide evidence of functional correlation among masticatory muscles
      and, indirectly, between changes to the interdental occlusal plane and
      modifications of the plantar arches due to talipes valgus and flat foot. In the
      two analysed conditions, the masticatory muscles undergo different functional
      alterations. This is due to the fact that the mechanoreceptors in the tendons of
      the muscles governing the plantar arch configuration are stimulated in different
      ways during the activation of long osteoarthromuscular chains. Dental specialists
      will have to take these correlation into account when diagnosing TMJ disorders.

PMID- 12201008
TI  - An EMG study on TMJ disorders.
AB  - The Authors have described a clinical case involving a patient with a classical
      TMJ syndrome and a full range of typical symptoms, both dental and non-dental.
      The patient underwent a set of EMG tests before his occlusal plane was restored
      using a special material, immediately following reconstruction and, lastly, three
      months following the application of a prosthesis. The findings of these EMG tests
      have shown that the complex symptoms reported by the patient could be traced back
      to his occlusal plane. Once it was reconstructed, all the typical dental and non
      dental symptoms of TMJ disorders subsided.

PMID- 12201009
TI  - [Determining factors in the wearing of a removable prosthesis: the role of
      familial example. Prosthetic risk: the influence of parental behavior].
AB  - The aim of the present study was to provide a fuller clarification of the
      influence of sociocultural and socioeconomic data on the bucco-dental ageing. In
      Particular, was suspected, the influence of the parental behavior towards the
      wearing of their own prostheses in the wearing of removable prostheses among the
      descendants. The study was led in a dental service (CHU of Marseille) on 260 from
      50 to 70 years old persons. Variables in the study were mainly basic
      sociocultural and socioeconomic variables (sex, age, educational level and social
      professional groups...); the dental morbidity (DMF); the periodontal state
      (corrected CPITN, plaque index, gingival index), the prosthetic state of the
      subjects, the prosthetic state of the parents, the behavior of the parents
      towards the port of their prosthesis (CPP), the behavior of the subjects in front
      of dental care. The data were analyzed mainly by the method of logistic
      regression. They indicated that the most determining variables concerning the
      wearing of removable prostheses were: the plaque index (OR = 1.730), the behavior
      in front of dental care (OR = 1.306) and especially, the parental prosthetic
      behavior (OR = 4.420). In others words, the fact that the parents had removable
      prostheses and well tolerated it, constituted an important risk factor so that
      the children had removable prostheses. It was here, according to the authors,
      about sociological and psychological determinants on the bucco-dental aging.

PMID- 12201010
TI  - The "impact factor" in the evaluation of research.
AB  - The "impact factor of journals", in brief IF, has become an important tool for
      the evaluation of research activities in certain disciplines, while it is gaining
      additional influence in others. Its widespread use is increasingly determining
      the fate of individuals, and academic departments. It is also contributing to
      restructuring of academic libraries and to reshaping the map of academic
      periodicals. There is no doubt that this index appears useful, and in many
      respects, attractive. It relieves faculty and administrators of the burden of
      reading and comparing papers and it seems to provide an "objective" criterion for
      judging scientific research. In this paper we present a different view and we
      argue that costs, in terms of potential damage to the scientific system, which
      are caused by an uncritical application of the IF, exceed by far its supposed
      merits. One purpose of this paper is to encourage scientists working in
      disciplines that have not yet been invaded by IF, (such as historians, jurists,
      social scientists and students of the humanities) not to be intimidated by the
      fact that other sciences are using IF to as a measure of research quality, and to
      carefully consider the implications of adopting such an index. This is not a
      study based on sophisticated statistical analysis. For such analysis we refer to
      the paper by Per O Seglen (a). Our criticism is based on "political"
      considerations, for which we deem observing reality with the naked eye to be
      sufficient.

PMID- 12201011
TI  - [Development of a flexible cardiorespiratory monitor based on induction
      plethysmography].
AB  - Induction plethysmography (IP) utilizes changes in the inductance of sinusoidal
      wires embedded in elastic bands placed around the chest and abdomen to detect
      volume changes in the two compartments. These changes can be attributed to
      respiration or heart beat. To date, most applications have been tailored to an
      investigation of respiration. More sensitive systems have been employed for the
      detection of cardiac activity. The wires within the bands, which function as the
      coil in a resonant circuit, are excited by an oscillator. Among other factors,
      the inductance of the coil depends on the cross-sectional area of the coie, and
      changes with respiration in coils placed around the chest and abdomen. Using
      LabView software, the biosignals obtained undergo an analog-to-digital conversion
      prior to processing. The system was calibrated using the isovolume method. In 10
      adults, IP was tested against a pneumotachograph (PNT) in different body
      positions (standing, sitting, supine, prone). Correlation between tidal volumes
      measured with IP and PNT was of r > or = 0.96 on average, recalibration being
      done after each change in position. The absolute mean error ranged between 3.7
      and 8.5%, depending on body position. The smallest error (3.7%) and greatest
      agreement between the two methods was found in the supine position (93.3% of the
      IP measurements within +/- 10% of the PNT measurements). An IP application that
      could be used to collect data over the long term and which is in good agreement
      with PNT was developed by employing a "virtual instrument" (VI, LabView) for
      flexible data acquisition and data processing. Agreement was best when the
      volunteer adopted a supine position. A smaller correlation was found in standing
      or seated subjects. This might be due to the fact that in the latter two
      positions, the respiratory system may have more than 2 degrees of freedom, and
      thus cannot be adequately monitored by only two bands around the thorax and
      abdomen. Signals produced by cardiac activity were detectable on the surface of
      the body.

PMID- 12201012
TI  - Automatic termination of radiofrequency energy upon catheter dislocation.
AB  - Since 1987 radiofrequency (RF) catheter ablation has proven to be an effective
      treatment for many cardiac arrhythmias. However, catheter dislocation during RF
      delivery may result in an unintentional heating of healthy non-arrhythmogenic
      tissue. Therefore, a device was developed (15 cm x 9 cm x 3 cm) consisting of a
      microprocessor, powered by a 9 V battery and to be connected between the
      indifferent cable of the RF generator and the patient's back electrode that
      continuously reads the electrode position information using a 3 dimensional
      electrode visualization system (LocaLisa). A red light indicates a sudden change
      in electrode position and an electronic switch is activated by the software to
      interrupt the connection between the indifferent electrode and the RF generator
      resulting in a high impedance shutdown and termination of RF energy delivery.
      Four different sensitivity settings (10 is most and 100 is least sensitive) can
      be selected and were tested in an in vitro tank setup during electrode dragging
      speeds of 0.5 to 20 cm/sec. For the sensitivity levels 10, 20, 50 and 100, an
      immediate termination of RF (Atakr II, Medtronic, 25 W) was demonstrated for an
      electrode dragging speed of greater or equal than 1, 2, 5 and 10 cm/sec,
      respectively. We conclude that the developed device may improve safety during
      ablation procedures of cardiac arrhythmias.

PMID- 12201013
TI  - [Afterload and blood pressure amplitude in dilated cardiomyopathy].
AB  - The beat-to-beat variability of the diastolic blood pressure induces small
      variations in the afterload of the left ventricle. These variations influence
      myocardial contractility, and thus blood pressure amplitude. We assessed the
      interdependence of blood pressure and changes in the afterload. We continuously
      recorded blood pressure (duration 200 s, at rest) in 20 patients with dilated
      cardiomyopathy (ejection fraction 32 +/- 13%, left ventricular diameter 67 +/- 8
      mm) and in 20 healthy volunteers. Interbeat intervals, diastolic pressures,
      systolic pressure amplitudes and mean slopes of systolic pressure amplitudes were
      measured. Correlation coefficients (r) were calculated to assess the
      interdependence of blood pressure amplitudes/mean systolic slopes and the
      preceding diastolic pressures/interbeat intervals, respectively. In healthy
      volunteers we found a strong interdependence between blood pressure amplitude and
      the preceding diastolic pressures (r = 0.62 +/- 0.21 and 0.47 +/- 0.22). Higher
      diastolic pressures were followed by higher blood pressure amplitudes, and by
      steeper slopes of the systolic peaks. In patients with dilated cardiomyopathy,
      such interdependence was significantly lower (r = 0.33 +/- 22 and r = 0.28 +/-
      0.35), and in patients with severely reduced left ventricular function (ejection
      fraction < 32%) was only marginal (r = 0.23 +/- 0.27 and 0.21 +/- 0.44,
      respectively). The forces of the isovolumetric contraction necessary to initiate
      the ejection phase of the left ventricle depend on the afterload, i.e. on the
      diastolic pressure. The responses of amplitude and slope of the systolic blood
      pressure to small changes in the afterload make it possible to assess left
      ventricular contractility. The latter is impaired in dilated cardiomyopathy.

PMID- 12201014
TI  - [Validation of the Tekscan system for statistic and dynamic pressure measurements
      of the human femorotibial joint].
AB  - In vitro dynamic pressure measurements in the healthy and pathologically altered
      knee joint help to improve our understanding of the loading pattern on
      femorotibial surfaces. The aim of the study was to evaluate a piezoresistive
      pressure measuring system. A human cadaveric knee was mounted in a material
      testing machine (Bionix 858) using a specially designed knee-holding device.
      Axial loading of the knee, flexed at 20o, at 500 N, 1000N and 1500 N was then
      carried out. For the static investigations, the piezoresistive measuring system
      (Tekscan), was compared with the FUJI measuring system. In addition, dynamic
      measurements were also performed with the Tekscan System. With the exception of
      the lateral compartment at a load of 1500 N, no differences in maximum pressures
      were observed between the two systems. Nor were there any differences with regard
      to contact surfaces, either in the medial or lateral compartment (p > 0.05).
      However, the reproducibility of the data was significantly higher with the
      Tekscan System (p < 0.01). Dynamic pressure measurements obtained with the knee
      flexed 20 to 90o showed that the lateral contact area shifted from anterior to
      posterior, while the medial contact area remained virtually unchanged. The
      Tekscan System proved to be more reliable than the FUJI System, and permits
      simultaneous measurements in both compartments. The Tekscan System is suitable
      for dynamic measurement of the femorotibial joint, and permits measurements to be
      made under more physiological conditions.

PMID- 12201015
TI  - [Experiments to determine the time dependent material properties of the
      periodontal ligament].
AB  - The periodontal ligament is a tissue that attaches the tooth (root) to its
      alveolar socket, and thus plays an important role in the regulation of tooth
      movements. Detailed knowledge of the material properties of the periodontal
      ligament is therefore essential to an understanding of tooth reaction to forces
      applied during orthodontic treatment. A knowledge of material parameters can also
      be used in simulations of long-term tooth movements with the aim of improving
      orthodontic treatment. To this end, this study investigated time-dependent
      material properties, namely the hysteresis behaviour of the periodontal ligament
      under constant-velocity loading, the influence of loading velocity on the
      hysteresis, and its failure under constant loading. Specimens obtained from pigs
      were used for testing purposes, and the experiments were conducted in a special
      test setup using a material testing device. The material behaviour of the
      periodontal ligament was shown to be viscoelastic, and the elastic parameters of
      material behaviour were also determined. Under constant-velocity loading,
      material behaviour showed a nonlinear course of the stress-strain curve, also
      known as hysteresis. When loading was repeated several times, the maximum stress
      of the hysteresis decreased with each cycle. Determination of the deflection of
      the specimen at different velocities showed maximum stress to be dependent on the
      loading rate. The measured stress-strain curves were approximated by bilinear
      behaviour, permitting the use of finite element calculations. Also investigated
      was the failure behaviour of the periodontal ligament, which revealed tissue
      rupture to be inconstant.

PMID- 12201016
TI  - Efficiency of fecal steroid hormone measurement for assessing reproductive
      function in the Hokkaido brown bear (Ursus arctos yesoensis).
AB  - The present study aimed to establish simple systems for measuring fecal steroid
      hormones in order to monitor the reproductive profiles of captive Hokkaido brown
      bears. The efficiency of fecal sample processing at the steps of dehydration and
      extraction and the correlation between steroid concentrations in matched fecal
      and blood samples were studied. Then, monthly changes in fecal estradiol-17 beta
      and progesterone in female bears, and testosterone in male bears were examined.
      The procedure was finalized as follows. Fecal samples were dried at 100 degrees C
      for 3 hr and extracted with diethyl ether. The diethyl ether in the extracts was
      evaporated and residues were reconstituted in ethanol for the assays. Hormone
      concentrations were quantified using enzyme immunoassays. Concentrations of
      progesterone and testosterone in fecal and plasma samples were correlated in the
      systems. The changes in fecal progesterone and testosterone concentrations were
      similar to those in serum concentrations of bears as reported previously. In
      contrast, fecal estradiol concentrations did not correlate with plasma levels
      probably because of the time lag in excretion. However, the changes in estradiol
      17 beta concentrations in feces in the present study were similar to those
      reported in serum. In conclusion, fecal progesterone and testosterone assay
      systems appear practical for monitoring ovarian and testicular activities without
      immobilization, though methodological improvements and further validation may be
      required. For the fecal estradiol-17 beta assay, there is a need to solve the
      problem of excretion time lag before the system can be used in the study of
      reproductive physiology.

PMID- 12201017
TI  - Excystation of Haplorchis taichui metacercariae could be elicited by change in
      pH.
AB  - The effect of different component of the intestinal fluid on the excystation of
      Haplorchis taichui metacercariae was examined in vitro. Encysted metacercariae
      obtained by pepsin digestion of fish muscle showed that the highest percentage of
      metacercariae excystation could be obtained after being treated with trypsin at
      pH 7.5. However, it was also observed that excystation of the metacercariae could
      also be effected by changing the pH to the basic condition. The most optimum pH
      for the metacercariae excystation was found to be 7.5. This method of obtaining
      the excysted metacercariae could prove to be useful for taxonomical study of
      trematode in general.

PMID- 12201018
TI  - Seroprevalence and molecular evidence for the presence of bovine immunodeficiency
      virus in Brazilian cattle.
AB  - Data on the worldwide distribution of bovine immunodeficiency virus (BIV) and
      bovine leukemia virus (BLV) is limited. A prevalence study of antibodies to BIV
      and BLV was conducted in six different cattle herds in Brazil. Out of a total of
      238 sera analyzed, 11.7% were found positive for anti-BIV p26 antibodies as
      determined by Western blot analysis, 2.1% were positive for anti-BLV gp51
      antibodies as detected by immunodiffusion test. Peripheral blood mononuclear
      cells from BIV seropositive cattle were found to have BIV-provirus DNA, as
      detected by nested polymerase chain reaction. A nucleotide sequence corresponding
      to a 298 bp fragment of the BIV pol gene was also analyzed. Amino acid sequences
      of these Brazilian pol gene products showed 98.0 to 100% homology to the American
      strain BIV R29, 97.0 to 99.0% to Japanese BIV isolates, and divergence ranged
      from 0 to 4.0% among Brazilian BIV isolates. This evidence of the presence of BIV
      and BLV infections in Brazil should be considered a health risk to Brazilian
      cattle populations and a potential causative agent of chronic disease in cattle.

PMID- 12201019
TI  - Serum IgG subclasses levels in paediatric patients with pneumonia.
AB  - OBJECTIVES: To determine the IgG subclass levels of patients admitted to Harare
      Central Hospital paediatric wards with pneumonia. DESIGN: A cross sectional
      study. SETTING: Harare Central Hospital, Departments of Immunology and
      Paediatrics, University of Zimbabwe; Department of Paediatric Immunology,
      University of Utrecht, The Netherlands. SUBJECTS: 56 paediatric patients. MAIN
      OUTCOME MEASURES: IgG subclass profiles of children with pneumonia. RESULTS: Of
      the 56 children tested, 40 (71%) had antibodies to human immunodeficiency virus
      (HIV). The levels of IgG1 and IgG3 subclasses were significantly higher in HIV
      antibody positive children (p < 0.001, p < 0.01 respectively) than in those
      without detectable HIV antibodies in their sera. There was no significant
      relationship between IgG subclass levels and the presence of HIV p24 antigen.
      Furthermore, age and gender also had no significant influence on the levels of
      IgG subclasses in this population. CONCLUSION: High levels of IgG1 and IgG3, but
      not IgG2 and IgG4, occur frequently in children with pneumonia and are associated
      with the presence of HIV antibodies.

PMID- 12201020
TI  - Reduced levels of chloroquine resistant Plasmodium falciparum in selected foci of
      the South West Province, Cameroon.
AB  - OBJECTIVES: To evaluate the state of chloroquine resistant malaria in the South
      West Province of Cameroon. To estimate the prevalence of different species of
      Plasmodium in the area. DESIGN: A cross sectional study. SETTING: South West
      Province of Cameroon. SUBJECTS: 326 febrile patients. MAIN OUTCOME MEASURES:
      Chloroquine resistance studies using the WHO seven-day standard in vivo test.
      Speciation of malaria by polymerase chain reaction. Prevalence of falciparum
      malaria by light microscopy of thick blood smears. RESULTS: Prevalence of
      chloroquine resistance ranged from 4.3 to 13.2%. A total of six cases showed RIII
      resistance, and three cases showed RII resistance. Plasmodium falciparum was the
      predominant species, 96.8% of those testing positive for P. falciparum, 6.3% of
      cases showed mixed infections of P. falciparum and P. malariae. P. ovale
      accounted for 3% of cases. CONCLUSION: P. falciparum resistance to chloroquine
      may not be on the increase compared to earlier reports from the South West
      Province. The results have important implications in treatment of malaria in view
      of the low cost of chloroquine.

PMID- 12201021
TI  - Antibiotic use in infants hospitalised with HIV-related pneumonia in Harare,
      Zimbabwe.
AB  - OBJECTIVE: To describe the clinical features of infants admitted with HIV-related
      pneumonia and to describe antibiotic use in relation to recommended treatment
      guidelines. DESIGN: Case series. SETTING: Paediatric medical wards of two
      University Teaching Hospitals, Parirenyatwa and Harare Central Hospitals.
      SUBJECTS: 100 infants aged one to 12 months admitted with HIV-related pneumonia.
      MAIN OUTCOME MEASURES: Mortality and antibiotic use in the two hospitals.
      METHODS: Records of 100 infants admitted for 48 hours or more with features of
      HIV-related pneumonia were analysed for clinical features and antibiotic use.
      RESULTS: 77% of patients were in the first six months of life with a peak age of
      two months and a median of four months (Q1 = 2, Q3 = 6). The median age of
      children admitted to Parirenyatwa hospital was 5.5 months (Q1 = 3, Q3 = 7) and in
      Harare hospital it was three months (Q1 = 2, Q3 = 6). The difference was
      statistically significant, p = 0.035. Fifty four percent of cases received
      penicillin, aminoglycoside and cotrimoxazole and overall only 30% of
      prescriptions complied with Essential Drug List of Zimbabwe (EDLIZ)
      recommendations for treatment of severe pneumonia in children with HIV infection.
      The overall mortality was 27.0%. The mortality in Harare Central Hospital was
      40.4% and 15.7% in Parirenyatwa. The difference was statistically significant p =
      0.005. CONCLUSION: The difficulties in establishing the cause of the pneumonia in
      infants with HIV infection was a contributory factor to lack of adherence to
      standard treatment guidelines. In countries with a high prevalence of HIV
      infection and with limited resources, a clinical case definition for Pneumocystis
      carinii pneumonia (PCP) is required as a measure to provide treatment for infants
      with HIV related pneumonia which is evidence based. This approach will also
      promote rational antibiotic prescribing and will contain cost.

PMID- 12201022
TI  - Anti-Salmonella activity of medicinal plants from Cameroon.
AB  - OBJECTIVES: To evaluate the effects of herbal extracts derived from plants
      commonly prescribed by traditional practitioners for the treatment of typhoid
      fever. DESIGN: A cross sectional study. SETTING: Departments of Life Sciences and
      Chemistry, University of Buea, Cameroon. SUBJECTS: Methanol extracts of plant
      parts commonly used in Cameroon for the treatment of typhoid fever. MAIN OUTCOME
      MEASURES: Antimicrobial activity was tested using the minimum inhibitory
      concentration (MIC) and the minimum bactericidal concentration (MBC) assays.
      RESULTS: Methanol extracts of plant parts commonly used in Cameroon for the
      treatment of typhoid fever were tested for antibacterial activity against
      Salmonella typhi, S. paratyphi and S. typhimurium. The formulations used were: 1)
      Formulation A comprising Cymbogogon citratus leaves, Carica papaya leaves, and
      Zea mays silk. 2) Formulation B comprising C. papaya roots, Mangifera indica
      leaves, Citrus limon fruit and C. citratus leaves. 3) C. papaya leaves. 4) Emilia
      coccinea whole plant. 5) Comelina bengalensis leaves. 6) Telfaria occidentalis
      leaves. 7) Gossypium arboreum whole plant. Antimicrobial activity was tested
      using the minimum inhibitory concentration (MIC) and the minimum bactericidal
      concentration (MBC) assays. Generally, Formulation A elicited inhibitory activity
      at a lower range of 0.02 to 0.06 mg/ml. Similarly, Formulation B elicited
      bacterial activity at the lowest range of 0.06 to 0.25 mg/ml. C. bengalensis
      leaves on the other hand, showed the lowest activity with a concentration range
      of 0.132 to 2.0 mg/ml and 1 to 4 mg/ml in MIC and MBC assays respectively. S.
      paratyphi was most sensitive to the formulations (concentration range of 0.02 to
      1 mg/ml in both MIC and MBC assays) while S. typhimurium was the least sensitive
      and concentrations of up to 4 mg/ml were required to be bactericidal. CONCLUSION:
      It is concluded that plant extracts with low MIC and MBC values (1 mg/ml and
      lower) may contain compounds with therapeutic activity.

PMID- 12201023
TI  - Ethics in reproductive health: clinical issues in Zimbabwe.
AB  - Reproductive health can present health practitioners with ethical problems
      because of the complex interaction between cultural practices, the laws of the
      country and individual personal preferences. In particular, the problems of
      pregnancy, sexually transmitted infections, family planning, sexual violence, and
      domestic abuse require a good knowledge of the laws of the country and the
      culture in which they operate. The practitioner should at all times respect the
      patient's autonomy and serve their best interests, whilst keeping in mind the
      legitimate interest of their partners, spouses, parents or guardians.

PMID- 12201024
TI  - Use of antimalarial drugs in Zimbabwe.

PMID- 12201025
TI  - Successful control of schistosomiasis in large sugar irrigation estates of
      Zimbabwe.
AB  - OBJECTIVE: To assess the impact of schistosomiasis control activities in Hippo
      Valley Sugar Estates. DESIGN: A situation analysis of schistosomiasis control
      activities in Hippo Valley Estates was made. Snail and parasitology data
      collected over 13 and 21 years respectively was analysed to determine the impact
      of control activities. SETTING: Only data collected in Hippo Valley Sugar Estates
      was analysed. MAIN OUTCOME MEASURES: Reduction in prevalence of schistosomiasis
      and snail population densities. RESULTS: Prevalence of Schistosoma haematobium
      reduced from over 50% in 1980 to below 10% in 2000. Similarly, prevalence of S.
      mansoni reduced from 25% in 1980 to below 10% in 2000. Over the years,
      prevalences for both S. haematobium and S. mansoni fluctuated but showed a
      general decline. Snail numbers in water bodies within the estates fluctuated over
      the years, dropping from over 100,000 snails in 1986 to about 10,000 snails in
      1998. The amount of niclosamid used to control snails varied over the years with
      less than 10 kg per year being used between 1995 and 1998. A marked improvement
      in safe water and sanitation facilities was noted. CONCLUSION: The significant
      reduction in prevalence and snail numbers suggests that the Hippo Valley Estates
      control programme has been successful. The success is attributed to chemotherapy
      and snail control supported by general improvement in safe water and sanitation
      facilities and health education.

PMID- 12201026
TI  - Antibiogram of Klebsiella pneumoniae isolates from Buea, Cameroon.
AB  - OBJECTIVE: To determine the antibiotic susceptibility of K. pneumoniae isolates
      from Buea, Cameroon. DESIGN: A prospective study of K. pneumoniae isolates from
      clinical samples of nosocomial origin. SETTING: A laboratory based investigative
      study at the Biotechnology Centres of the Universities of Buea and Yaounde 1,
      Cameroon, and three Buea based hospitals. K. pneumoniae isolates were obtained
      from sputum, wound swabs and urine and screened for their antibiogram using
      standard procedures. RESULTS: Results on the antibiogram showed seven distinct
      antibiotypes distinguished by different susceptibilities to aminoglycosides
      (Spectinomycin and Gentamicin), Chloramphenicol and Augmentin. All the isolates
      shared multi-resistance to Amoxicillin and Trimethoprim. However, the isolates
      showed marked susceptibilities to Norfloxacin (90.01%), Cefuroxime (95.45%) and
      Ciprofloxacin (86.36%). CONCLUSION: The study has revealed that K. pneumoniae
      isolates in the environment of Buea, Cameroon are multi-drug resistant. This
      finding is of clinical and epidemiological significance.

PMID- 12201027
TI  - Model for assessment of endothelial cell function and viability using the MTT dye
      test and [3H].
AB  - OBJECTIVES: To establish a reproducible in vitro model for evaluating endothelial
      cell function in clinical disease states. DESIGN: A prospective study of human
      umbilical vein endothelial cells (HUVEC) isolated and cultured. SETTING:
      Department of Haematology, University of Yaounde I, Cameroon and Department of
      Medicine University of Newcastle-upon-Tyne, England. RESULTS: The optimum initial
      cell seeding concentration, for maximal conversion of the formazan dye was 40 x
      10(3) cells/well, after 24 hours incubation. At concentrations above 40 x 103
      cells/well some inhibition of dye conversion occurred. The conversion of formazan
      dye was directly proportional to cell numbers for the first 48 hours only, at all
      cell concentrations. Thereafter, cell metabolism appeared to be inhibited. Third
      passage endothelial cells (ECs) were exposed to a range of lipopolysaccharide
      (LPS) concentrations for one and 24 hours, prior to performing the MTT dye test.
      Dye conversion was observed after one hour at even the lowest concentration of
      LPS (0.1 microgram/ml), to 49.9% +/- 5.6% of unperturbed control EC, with 10 x
      10(3) initial seeding numbers. After 24 hours perturbation a small but
      statistically significant further inhibition was observed. [3H] thymidine
      incorporation studies indicated that the lowest LPS concentration tested (0.1
      microgram/ml) had a stimulatory effect on DNA synthesis at the higher cell
      concentration (20 x 10(3) cells/well). In the range of 1 to 100 micrograms/ml of
      the LPS tested, there was increased DNA synthesis at all cell numbers.
      CONCLUSION: The model may be used to monitor the effects of other agents which
      are known to, or could be associated with, alterations in endothelial cell
      function and will serve in mimicking clinical situations including hyper
      coagulable states.

PMID- 12201028
TI  - Medical negligence is very much in the news these days.

PMID- 12201029
TI  - Longstanding retained foreign bodies in the cranium: a short case report.
AB  - Two cases of longstanding retained cranial foreign bodies treated surgically are
      reported. Patients with longstanding retained foreign bodies may remain
      clinically well until complications arise. This report emphasizes the importance
      of maintaining clinical suspicion in mild head injured patients presenting with
      open scalp wounds, and the value of skull radiographs.

PMID- 12201030
TI  - Endometriosis presenting as an obstructed femoral hernia: a case report.

PMID- 12201031
TI  - Earliest presenting sign and morbidity profile of sickle cell disease patients
      attending the adult SCD clinic at the UCH Ibadan, Nigeria.

PMID- 12201032
TI  - Drug addiction as drive satisfaction ("antidrive") dysfunction.
AB  - Drug addiction is a complex brain disorder, characterized by the loss of control
      over drug seeking and drug taking behavior, and by the risk of relapse, even
      after a prolonged period of abstinence. This disorder may have its source in a
      disturbed balance of drive-related behaviors, which control appetitive reactions
      aimed at seeking contact with an addictive substance. The act of consumption
      becomes more and more attractive, and the behavior takes on compulsive character.
      We suppose that drug addiction may involve a change in the mechanism of
      satisfaction of drives and states of satiation as well. To understand how the
      motivational processes are changed with the development of dependence, one must
      consider the mechanism of drive satisfaction and satiation states that occur in
      relation to the consumatory reflex. When a given drive is satisfied a state of
      fulfillment occurs. This state may be a result of a so-called "antidrive"
      mechanism (Konorski 1967). While a drive activity is characterized by general
      activation and tension, the drive satisfaction state ("antidrive") is
      characterized by relaxation and relief. When a particular drive is satisfied, the
      operation of other drives become possible. Therefore, we postulate that
      dysfunction of drive satisfaction leads to the sustained activation related to
      the current drug-related drive, which blocks the operation of other drives. In
      effect, uncontrolled compulsive appetitive behavior is released, and the
      operation of other drives is restrained, thus forcing the organism to focus on
      drug-related drive. The reason for an "antidrive" dysfunction may be related to
      adaptive changes which develop during a contact with an addictive substance.

PMID- 12201033
TI  - Involvement of MMPs in delayed neuronal death after global ischemia.
AB  - Spatial and temporal relations between metalloproteinase (MMP-2 and MMP-9)
      activation and laminin degradation in gerbil hippocampus after transient cerebral
      ischemia has been studied. Activity of MMPs was determined by gelatin zymography
      in homogenates from dorsal (DP, an equivalent of CA1 sector) and abdominal (AbP,
      containing CA2-4 and gyrus dentatus) parts of hippocampus. A significant
      activation of both investigated metalloproteinases was found at 72 h of recovery.
      Whereas MMP-2 up-regulation did not show any spatial preferences, the increase of
      MMP-9 activity was observed exclusively in DP. Activation of MMP-9 at this time
      point correlated spatially with degradation of laminin-protein of extracellular
      matrix. These results show that MMP pathway may function as a component of
      delayed neuronal death cascade in the apoptogenic CA1 sector after transient
      global ischemia.

PMID- 12201034
TI  - Fear behavior and regional brain monoamines distribution after R(+)-8-OHDPAT and
      R(+)-UH-301 injections into the dorsal raphe nucleus in rats.
AB  - The effects of 8-OHDPAT and UH-301 injection into the dorsal raphe nucleus (DRN)
      on fear behavior of the light-dark transitions test and regional brain monoamines
      (NA, DA, 5-HT) and their metabolites (MHPG, DOPAC, 5-HIAA) in the hypothalamus
      (HPT), midbrain central gray matter (MID), amygdala (AMY), hippocampus (HIP) and
      pons (PO) were examined. An injection of 8-OHDPAT (300 ng) as well UH-301 (300
      ng) into the DRN evoked an increase in the number of head dipping from dark to
      the illuminated compartment of chamber, an increase of time of motionless in the
      dark compartment and decrease of time of locomotion activity in the illuminated
      compartment. HPLC analysis showed reduction of 5-HIAA/5-HT ratio in the HPT, HIP
      and PO, increase of MHPG/NA ratio in the HIP and PO, and increase of DA content
      in the HPT, AMY and HIP after 8-OHDPAT injection. But injection of UH-301 reduced
      5-HT in the MID and increased in the AMY, reduced 5-HIAA content in the HIP and
      increased in the MID and decreased MHPG/NA ratio in the PO. These results
      indicate that both 5-HT1A receptor agonists, acting on the 5HT1A autoreceptors
      caused the anxiolytic effects, reduced fear behavior on the rat connected with
      infringement of dynamic balance between the serotonergic and catecholaminergics
      systems.

PMID- 12201035
TI  - Behavioural responsiveness to amphetamine or scopolamine following repeated
      exposure to chlorphenvinphos in rats.
AB  - A number of reports indicate that exposure to organophosphates (OPs), inhibitors
      of acetylcholinesterase (AChE), may result in long-lasting neurobehavioural
      alterations suggestive of an increased cholinergic tone. It is known that rats
      with cholinergic hyperreactivity are behaviourally hyposensitive to cholinergic
      antagonists and dopaminergic agonists. The purpose of the present study was to
      find out whether a similar trait would develop in rats exposed to
      chlorphenvinphos (CVP), an OP pesticide, in the past. The rats were given ten
      daily i.p. injections of CVP at doses of 0.5 mg/kg (group P-0.5) or 1.0 mg/kg
      (group P-1.0). The locomotion stimulating effect of i.p. injection of 1.0 mg/kg
      amphetamine (AMPH), or 0.7 mg/kg scopolamine (SCOP), was assessed on postexposure
      day 21 (group P-0.5) or 42 (group P-1.0), i.e. after a time sufficient for AChE
      recovery. The assessment revealed that in group P-1.0 the behavioural response to
      AMPH and SCOP was significantly depressed. In rats of the P-0.5 group, however,
      the behavioural response to each of the drugs was increased. The results suggest
      that, depending on the exposure level, contrasting alterations in some
      neurotransmitter systems may be induced by repeated exposure to CVP.

PMID- 12201036
TI  - Correlation between long latency evoked potentials from amygdala and evoked
      cardiac response to fear conditioned stimulus in rats.
AB  - We investigated relation between activity of central nucleus of amygdala (CE) and
      phasic heart rate deceleration during differential fear conditioning. We found
      that P2 component of long-lasting event potential (EP) to CS+ but not to CS-
      correlated strongly with HR deceleration in the 1st second after stimulus onset.
      The obtained results are discussed in the light of LeDoux's and Kapp's findings
      showing crucial role of amygdala in processing of emotionally relevant
      stimulation and it's involvement in initiating autonomic responses.

PMID- 12201037
TI  - Behavioral sensitization to amphetamine induced by a single i.p. dose of
      oxotremorine in the rat.
AB  - Earlier experiments have revealed that rats treated with a single dose of
      chlorphenvinphos (CVP), an irreversible acetylcholinesterase inhibitor, are
      hyposensitive to amphetamine (AMPH) given three weeks after CVP. Exposure to CVP
      results in an excess of acetylcholine with subsequent overactivation of the
      nicotinic as well as muscarinic cholinergic receptors. The purpose of the present
      experiment was to find out whether a selective activation of muscarinic receptors
      could induce behavioral hyposensitivity to AMPH. To attain this purpose, male
      rats were pretreated once with 0.00, 0.135, 0.27 or 0.55 mg/kg of oxotremorine, a
      muscarinic agonist, and challenged 15 days later with 1.0 mg/kg dose of AMPH. The
      pre- and postinjection open-field behavior of the rats was tested with the use of
      a computerized set of activity meters. The testing revealed that in oxotremorine
      pretreated animals the behavioral response to AMPH, i.e. increase in the
      ambulatory activity, was not diminished but, to the contrary, it was augmented.
      This effect was dose-dependent, being most pronounced in rats given the 0.55
      mg/kg of oxotremorine. The possible cause of the difference between the effect of
      CVP and oxotremorine is discussed.

PMID- 12201038
TI  - Affective percept and voluntary action: a hypothesis.
AB  - I present a hypothesis concerning the neuronal, mental and behavioral effects of
      all kinds of affective (emotional) stimuli, i.e., of unpleasant and pleasant
      stimuli. I use the term stimulus in its broad sense. Affective stimuli evoke two
      associated percepts: "cognitive" and "affective". A food in the mouth, for
      example, evokes the gustatory percept and the percept of pleasure. However,
      affective percepts are unstable parts of cognitive-affective compounds. Five
      types of affective percepts are pain, fear, pleasure, "desire" and appetite in
      the broad sense of these words. Desire is evoked by inadequate pleasant stimuli.
      Affective percepts are "lower" or "higher". The latter are not directly
      associated with bodily needs. Esthetic and social percepts are higher, for
      example. Although pain and pleasure are essentially innate, they can be modified
      by sensory experience. Alimentary and esthetic preferences and social values are
      modifiable, for example. The neurons of pain and fear and of the unpleasant
      components of desire and appetite motivate four types of voluntary actions. These
      are, respectively, escape, avoidance, "optimization" and approach actions. All
      these actions eliminate the motivating displeasure. In addition, avoidance
      actions protect from the signaled pain, optimization actions increase the
      existing pleasure and approach actions provide the signaled pleasure. Thus,
      voluntary actions associated with different percepts occur according to one
      universal principle. Voluntary actions are "internal" and behavioral. During
      internal actions a goal and then an action plan are decided. These actions often
      provide the images of the goal stimuli and of particular movements.

PMID- 12201039
TI  - On the intrinsic innervation of the epididymis of the camel (Camelus
      dromedarius).
AB  - The innervation of the camel epididymis was studied in 26 apparently healthy,
      sexually mature animals aged between 4 and 12 years. The material was collected
      during the different seasons of the year. Generally, five samples were taken from
      each epididymis. To demonstrate the general innervation pattern,
      immunohistochemical reactions to protein gene product-9.5, neurofilaments and
      neuron-specific enolase were used, in addition to acetylcholinesterase
      histochemistry. The nerve supply of the epididymis comes from two sources: (1)
      The majority of fibers come from the N. spermaticus inferior and accompany the
      deferent duct. (2) Another contribution stems from the N. spermaticus superior
      and enters the head region of the epididymis. From the exterior, the nerves
      penetrate the capsule of the organ to reach the interductular connective tissue.
      The terminal ramifications are observed directly within the wall of the duct and
      the wall of the epididymal arteries. The veins of the camel epididymis are not
      innervated. In the wall of the ductus epididymidis, the nerve fibers form
      plexuses at the subepithelial level and in the muscular coat. The amount of nerve
      fibers increases from the head to the tail, paralleling an increase in the
      intrinsic musculature. The intramural and interductular innervation of epididymal
      body and tail shows clear seasonal variations: More fibers and stronger reactions
      are observed during the winter season; the lowest density and the weakest
      reactions occur during the summer season. All epididymal nerves of the camel are
      unmyelinated. The majority of the intramural fibers and all in the arterial wall
      represent postjunctional sympathetic axons, but in the intramural plexuses of the
      duct a considerable number of cholinergic fibers are also present. Neuropeptide Y
      is the most frequent peptidergic transmitter and generally co-localized with
      dopamine-beta-hydroxylase in the sympathetic axons. Vasoactive intestinal
      polypeptide has a distribution similar to that of the cholinergic fibers.
      Calcitonin gene-related peptide-positive axons occur in moderate numbers, but
      never in the arterial innervation. Together with the relatively rare substance P
      containing fibers, the calcitonin gene-related peptide-positive axons seem to
      represent the only sensory nerves in the camel epididymis.

PMID- 12201040
TI  - A cell-seeded biocomposite for cartilage repair.
AB  - Chondrocytes in monolayer cultures lose their phenotype and capability to express
      type-II collagen, they dedifferentiate into a fibroblastic cell type. Using three
      dimensional culture systems a redifferentiation of these cells may occur. In the
      present study we investigated the morphology and biosynthetic activity of human
      articular chondrocytes seeded on porous matrices of type I/III collagen
      (Chondrogide, Geistlich Biomaterials, Wolhusen, Switzerland). Microscopical
      examinations showed that chondrocytes adhere firmly to a collagen-I/III-membrane
      exhibiting their characteristic spherical cell shape. Cell numbers after
      enzymatic digestion of the membrane showed a 93% recovery of seeded cells.
      Immunohistological examination revealed positive staining for type-II collagen in
      some areas. The generated biocomposite withstands mechanical stress, keeps its
      size and design and does not shrink in culture. It is therefore easy to handle,
      can be sutured, glued or fixed with pins. This study shows, that in vitro
      production of autologous cartilage-like tissue could be established using a
      bilayer collagen type I/III fleece. This biocomposite carries active chondrocytes
      and is currently being evaluated in vivo in a sheep model as well as in a
      clinical trial for the repair of localized cartilage defects in the knee.

PMID- 12201041
TI  - Apoptotic chondrocyte death in cell-matrix biocomposites used in autologous
      chondrocyte transplantation.
AB  - Tissue engineering may be a promising approach for the treatment of focal
      articular cartilage defects. Programmed cell death (apoptosis) plays an important
      role in multiple degenerative processes of cartilage (e.g. osteoarthritis). It is
      known that matrix provides a trophic signal for the cells and an altered matrix
      may influence the availability of factors that regulate apoptosis. In this study
      we investigate the viability of chondrocytes seeded on a Chondrogide scaffold
      (Geistlich Biomaterials, CH), which we use in matrix-induced autologous
      chondrocyte transplantation (MACT). By now, we have studied material from 29
      patients treated for localized articular cartilage defects in the knee. Our
      results indicate that light microscopy (Mayer's hematoxylin-eosin, Masson
      Goldner, Trypan-blue and TUNEL method) and electron microscopy can be used to
      investigate for apoptotic cells grown on a Chondrogide resorbable scaffold.
      Neither the handling of the cell-matrix biocomposite nor the procedures for
      fixation could destroy the scaffold or the cell sheet adhering firmly to the
      matrix. Apoptotic cells were revealed in all samples and with all techniques
      used. Mayer's hematoxylin-eosin and Masson-Goldner staining show cells with a
      condensed, pycnotic nucleus and shrunken cytoplasm. In electron microscopy we
      observed cells with chromatin condensation and volume shrinkage consistent with
      apoptosis. The results of the Trypan-blue staining show a mean viability of 92.1
      +/- 9.8% (range 57-100%). The TUNEL method revealed 44.6 +/- 20.4% positive
      cells. Our results indicate that apoptosis plays an important role in
      chondrocytes grown on a scaffold. An optimal scaffold will determine the growth,
      morphology and phenotype of the chondrocytes by its physical and chemical
      characteristics.

PMID- 12201042
TI  - Histochemical study of perineuronal nets in the retrosplenial cortex of adult
      rats.
AB  - The retrosplenic cortex of rats, similar to many cortical or subcortical regions,
      is provided with special subsets of neurons that exhibited a fenestrated or
      reticular coat of condensed extracellular matrix on their soma, initial dendrites
      and proximal axon segment. This pericellular coating, currently termed
      "Perineuronal Nets", was detected on the surfaces of some neurons distributing
      throughout the cortical layers II-V. They presented direct interconnections with
      each other, and appeared in close association to the astroglial processes. In
      addition to their collagenous ligands, the perineuronal nets (PNs) were enriched
      with proteoglycans (PGs, sulfated glycoconjugates) and/or glycoproteins (GPs,
      unsulfated glycoconjugates with terminal N-acetylgalactosamine). Accordingly, the
      PNs were differentially identified as belonging to three categories, depending
      upon their organic nature or chemical composition. First, coats exclusively
      formed of PGs (stained with iron colloid); second, coats formed of GPs (labeled
      with plant lectins binding to terminal N-acetylgalactosamine); and third, complex
      coats formed of PG networks intermingled with glycoprotein molecules (double
      stained with iron colloid and lectin). Since differential distribution of protein
      containing substances (GPs and/or PGs) in the extracellular matrix contributes to
      functional terms, we suggest that these biochemical or morphological differences
      in the microenvironment of some retrosplenial neurons might reflect certain
      functional aspects concerned with processing of navigation or episodic memory.

PMID- 12201043
TI  - Morphological characterization of the female prostate (Skene's gland or
      paraurethral gland) of Lagostomus maximus maximus.
AB  - The Skene's (paraurethral) gland is the histologic homologue to the male
      prostate. Much experimental work has been done on women and on various rodents.
      In this study we describe for the first time the anatomical and histological
      characteristics of the paraurethral gland in the plain viscacha (Lagostomus
      maximus maximus). This gland is formed by tubuloalveolar adenomers surrounded by
      connective tissue and smooth muscle fibers. The adenomers are lined by cuboidal
      or columnar epithelium. In the lumen of the adenomers, PAS positive secretions
      could be detected. The conduits are lined by bi-stratified epithelium. In some
      aspects this gland is similar to that of other mammals.

PMID- 12201044
TI  - Fine structure of the 7 postnatal days Calomys callosus palatine salivary glands.
AB  - The aim of this study has been to determine the ultrastructural characteristics
      of the minor palatine salivary glands on the seventh day of development and to
      demonstrate wether their secretion is mucous, serous or seromucous by light,
      transmission and scanning electron microscopy. This study has shown that the
      palatine gland acinar cells are predominantly mucous with some serous units.
      These cells contain electron dense (serous) and low electron dense (mucous)
      granules in the apical portions. The cytoplasmatic organelles like mitochondria,
      Golgi apparatus and rough endoplasmic reticulum are localized in a supranuclear
      portion. We could also observe the flattened myoepithelial cells surrounding the
      basal part of the acini with myofilaments, Golgi apparatus and mitochondria.
      Desmosomal junctions and membrane interdigitations are present between the acinar
      and the myoepithelial cells. A basal lamina, divided in two layers, an electron
      dense and an electron lucent is present between the glandular stroma which is
      composed of dense connective tissue and the endpieces.

PMID- 12201045
TI  - A new plastination technique for head slices containing brain.
AB  - The results of plastination of head slices are unsatisfactory when muscles,
      connective tissue and the brain are impregnated with one and the same resin. The
      epoxy- or polyester-plastination technique renders transparent either the head
      without the brain (e.g. E 12) or the brain without the adjacent tissues (e.g. P
      40). A new technique is described which allows a homogenous transparency of both
      the head and the brain.

PMID- 12201046
TI  - Histological findings of bone remodeling around smooth dental titanium implants
      inserted in rabbit's tibias.
AB  - Nowadays, there are many kinds of implants with different covering layers. The
      aim of these wide spectra is to discover the material that has the best possible
      biocompatibility. The presence of so many kinds of covering layers indicates that
      this aim has not been reached until now. The implant anchorage in the bone is
      very important for the stability of the element that has to support much pressure
      when under use. As it is known, the implant/bone interface does not present the
      ideal result expected by all professionals. In the laboratory there are
      possibilities of researching many kinds of implants--under different techniques
      of insertion. This will lead to the best methods and materials available.
      Titanium is the basic material used by many authors and needs no further
      discussion. So far it is the material with the best biocompatibility. The aim of
      this work is to observe and study the bone healing in the interface between a
      titanium implant and bone under light microscopic technique. Commercial pure
      titanium implants with a smooth surface were inserted in rabbit's tibias where
      they remained for eight weeks. The amount of bone inside the implant threads was
      quantified by the use of a stereologic method. The histological results indicated
      that an intense remodeling process of the cortical bone was found close to the
      implant surface and in the stereometry a higher amount of the new bone formation
      was also observed in the cortical tibia at the implant/bone interface.

PMID- 12201047
TI  - Histology of the bone-tendon interfaces of limb muscles in lizards.
AB  - Lizards exhibit continual bone growth at the epiphysis, and their limb muscles
      are distributed differently from those of mammals because of differences in
      weight bearing. We therefore characterized the bone-tendon (B-T) interface (also
      termed the enthesis) in lizards. Using the forelimbs of five monitor lizards and
      three iguanas, we performed histological investigations on 57 B-T interfaces.
      Most reptilian tendons were very short and were often composed of wavy fiber
      bundles. Fibrocartilage (FC)-mediated direct insertion was observed at all
      epiphyses, whereas periosteum-mediated indirect insertions, including fleshy
      attachments, were often located on the flat surfaces of the pectoral girdles and
      at the diaphyses of the limb bones. The reptilian B-T interface was characterized
      by variability in the morphology of the FC-mediated insertions, especially by
      morphologies intermediate between those of FC- and periosteum-mediated
      interfaces; i.e., 1) various degrees of absence of the clear FC zonation seen in
      mammals, including the tidemark; 2) involvement of the periosteum in the FC; 3)
      the presence of various types of FC cells in the tendon near the interface, to
      reinforce the tendon against compression or shear stress; and 4) both FC and
      hyaline cartilage (lateral articular cartilage) receiving the tendon at the
      epiphysis. Overall, variations in the connective tissue, especially the FC
      tissue, were very evident in the reptilian B-T interface. The specific structures
      of the interfaces probably represent adaptations to the continuous growth and
      loose joint structures of lizards.

PMID- 12201048
TI  - Functional adaptations of facet geometry in the canine thoracolumbar and lumbar
      spine (Th10-L6).
AB  - The shape, size and transverse distance between contralateral caudal articular
      processes of caudal thoracic and lumbar vertebrae were evaluated in a sample of
      140 macerated canine spines to contribute to the understanding of the development
      of vertebral misalignment. Dogs were grouped as large, chondrodystrophic, and
      small breeds. In large dogs, caudal articular surfaces were adapted to higher
      body-weight by the presence of larger articular surfaces. Additionally, caudal
      articular surfaces not only covered the lateral, but also the ventral (i.e.
      ventral facet) and/or caudal aspects (i.e. caudal facet) of the caudal articular
      processes. Ventral facets, which increase loading capacity of the zygapophyseal
      joints in normally aligned vertebrae, were more frequently observed in large
      breeds (p < 0.001) than in small and chondrodystrophic breeds. With some
      exceptions, caudal facets primarily were present in large dogs, especially at the
      vertebral levels L3-L5. Their formation is induced by extension of the normal
      lykphotic thoracic and lumbar spine causing lumbar lordosis and denotes loss in
      elasticity of the bow-and-string-construction of the trunk. Because ventral and
      caudal facets are consistent with convexity of the caudal articular surfaces,
      which to a great degree was noted to result in formation of ball-and-socket
      joints, spinal stability is supposed to be decreased under such conditions.

PMID- 12201049
TI  - Anomalous lumbrical muscles arising from the deep surface of flexor digitorum
      superficialis muscles in man.
AB  - During anatomy practice in 1999 at Kumamoto University School of Medicine, the
      anomalous lumbrical muscles originating in the forearm were observed in both arms
      of a cadaver. These muscles, originating from the intermediate tendon of the deep
      layer of the flexor digitorum superficialis for the index finger (FDS-II), passed
      through the carpal tunnel to join the insertion of the first lumbrical muscle,
      and formed a muscle belly near the origin in the left and at the insertion in the
      right. The left anomalous muscle was innervated by a branch of the median nerve
      just proximal to the carpal tunnel. The right one received a twig from the nerve
      to the first lumbrical muscle. Tracing the nerve fibers by peeling off the epi-
      and perineurium clarified that the nerve fibers supplying the left anomalous
      muscle formed a common bundle with the fibers to the first lumbrical muscle.
      Therefore, these anomalous muscles are considered to be the accessory lumbrical
      muscles arising from the forearm. The three accessory lumbricalis, including one
      case reported by Yamada (1986), received branches which had slightly different
      origins from proximally (nerve to the distal belly of FDS-II) to distally (nerve
      to the first lumbricalis). Accordingly the position of the muscle belly shifted
      distally. The occurrence of these unusual accessory lumbrical muscles indicates
      that the distal belly of FDS-III and the first lumbricalis are derived from a
      common muscle origin and presents an important clue to the phylogenetic origin of
      the flexor digitorum superficialis.

PMID- 12201050
TI  - A new device for measuring mastication force (Gnathodynamometer).
AB  - This work presents a new device, developed and constructed for the determination
      of the masticatory forces. Our new apparatus worked well in measuring maximal
      bite force and masticatory efficiency of incisor and molar teeth, respectively.
      The obtained results related to intraoral forces were very similar to the values
      previously given in the literature.

PMID- 12201051
TI  - Angioarchitectural characteristics of the anterodorsal surface of aging and young
      rabbit tongue: scanning electron microscopy study.
AB  - The three-dimensional angioarchitecture of young and aging rabbit tongues were
      studied using a vascular corrosion cast method. The vascular network of different
      lingual papillae were observed by scanning electron microscope (SEM). Young
      animals showed filiform papillae distributed all over considered area, with
      fungiform ones among them. In comparison to developed specimens, young rabbits
      demonstrated dense and higher organization of microvascular network.

PMID- 12201052
TI  - Morphology of the large intestine of the pig: haustra versus taenia.
AB  - The aim of the present study was to compare the morphological characteristics of
      the taenia and haustra of the large intestine in pigs. Ten pigs were fed a
      barley/wheat-based diet for a period of five weeks. Tissue samples were taken
      from the cecum and the proximal part of the colon at slaughter and processed
      histologically for determination of crypt volume, depth and density of the
      crypts, thickness of muscularis externa, and carbohydrate histochemistry. In all
      parameters examined regional differences in mucosal architecture of the cecum and
      proximal colon were demonstrated. Apparently, the regional differences in mucosal
      architecture between taenia and haustra were more pronounced in the cecum than in
      the proximal colon. The regional variation in mucin characteristics and in crypt
      parameters could be explained by differences in functional status and/or in the
      local environment. As all the parameters investigated in this study are not only
      dependent on sampling site, but also, e.g., on type of diet and its physical
      form, great care must be taken to obtain tissue from comparable sites in all
      animals in experimental studies to avoid incorrect conclusions.

PMID- 12201053
TI  - Formation of ionization clusters in nanometric structures of propane-based tissue
      equivalent gas or liquid water by electrons and alpha-particles.
AB  - Despite the importance of ionization yield formation in sub-cellular structures a
      few nanometres in size, with regard to radiation damage our present knowledge in
      this respect is almost exclusively based on Monte Carlo simulations which in turn
      are based on cross section sets for water vapour or liquid water. Experimental
      data, although urgently needed, are still missing because the direct measurement
      of ionization yields in sub-cellular structures or, at least, in nanometric
      volumes of liquid water, is not yet possible. The best feasible way to overcome
      this problem of measurement at present, is the use of highly sophisticated
      counters filled with gases at low operating pressure to simulate target volumes a
      few nanometres in diameter at unit density. An indispensable prerequisite of the
      reliability of such measurements is, however, a check of the equivalence of the
      ionization yield produced in a specified target gas and the yield to be expected
      in liquid water or biological material. For this purpose, the ionization yield
      formation by electrons and alpha-particles in liquid water was simulated using
      the Monte Carlo method and compared with that produced in propane-based tissue
      equivalent gas (composition by volume 55% C3H8, 39.6% CO2, 5.4% N2). After a
      short summary of the most important physical aspects of ionization cluster
      formation, new results are presented and discussed from the point of view of
      radiation physics and radiation biology.

PMID- 12201054
TI  - Risk coefficient for gamma-rays with regard to solid cancer.
AB  - A previous investigation has uncoupled the solid cancer risk coefficient for
      neutrons from the low dose estimates of the relative biological effectiveness
      (RBE) of neutrons and the photon risk coefficient, and has related it to two more
      tangible quantities, the excess relative risk (ERR1) due to an intermediate
      reference dose D1 = 1 Gy of gamma-rays and the RBE of neutrons, R1, against this
      reference dose. With tentatively assumed RBE values between 20 and 50 and in
      terms of organ-averaged doses--rather than the usually invoked colon doses--the
      neutron risk factor was seen to be in general agreement with the current risk
      estimate of the International Commission on Radiation Protection (ICRP). The
      present assessment of the risk coefficient for gamma-rays incorporates--in terms
      of the unchanged A-bomb dosimetry system, DS86--this treatment of the neutrons,
      but is otherwise largely analogous to the evaluation of the A-bomb data for the
      ICRP report and for the recent report of the United Nations Scientific Committee
      on the effects of ionizing radiation, UNSCEAR. The resulting central estimate of
      the lifetime attributable risk (LAR) for solid cancer mortality is 0.043/Gy for a
      working population (ages 25-65), and is nearly the same whether the age at
      exposure or the attained age model is used for risk projection. For a population
      of all ages 0.042/Gy is obtained with the attained age model and 0.068/Gy with
      the age at exposure model. The values do not include a dose and dose rate
      effectiveness factor (DDREF), and they are only half as large as the new UNSCEAR
      estimates of 0.082/Gy (attained age model and all ages) and 0.13/Gy (age at
      exposure model and all ages). The difference is only partly due to the more
      explicit treatment of the neutrons. It reflects also the fact that UNSCEAR has
      converted ERR into LAR in a way that differs from the ICRP procedure, and that it
      has summed the overall risk coefficient for solid tumor mortality and incidence
      from separate estimates for eight solid tumor categories, whereas the present
      study employs a combined computation for all solid tumors and uses the ICRP
      procedure for the conversion of ERR into LAR. The appendix gives results for the
      solid cancer incidence data.

PMID- 12201055
TI  - Estimates of radiological risk from a terrorist attack using plutonium.
AB  - The possible use of radioactivity dispersal devices by terrorist groups has been
      recently reported in the news. In this paper, we discuss the threat of terrorist
      attacks by plutonium, with particular attention to the dispersal of plutonium by
      explosion or fire. Doses resulting from inhalation of radioactive aerosol induced
      by a plutonium explosion or fire are simulated using a Gaussian plume model (the
      HOTSPOT code) for different meteorological conditions. Ground contamination and
      resuspension of dust are also considered in the simulations. Our simulations
      suggest that acute effects from a plutonium dispersal attack are very unlikely.
      For late stochastic effects, the explosion poses a greater hazard than fire.
      However, even in the worst-case scenario, the dispersed plutonium would cause
      relatively few excess cancers (around 80 in a city of 2 million inhabitants)
      after many years from the explosion, and these excess cancers would remain
      undetected against the background of cancer fatalities.

PMID- 12201056
TI  - Alterations in the cell cycle and in the protein level of cyclin D1, p21CIP1, and
      p16INK4a after exposure to 50 Hz MF in human cells.
AB  - The effect of exposure to 50 Hz, 1 mT magnetic fields (MF) on the cell cycle in
      general, on the DNA synthesis in S-phase, and on the G1-phase regulating proteins
      Cdk4, cyclin D1, p16INK4a, and p21CIP1 was investigated in human amniotic fluid
      cells. The BrdU-incorporation assay revealed a significant diminution of S-phase
      cells in MF-exposed cultures. The protein level of Cdk4 did not change, but MF
      induced a decreased expression of cyclin D1 after 24 h and 30 h exposures. The
      level of p16INK4a increased at 1 h and 12 h after exposure, whereas the
      expression of p21CIP1 was enhanced at 6 h and 12 h after exposure. Reduced levels
      of both Cdk inhibitors were observed at longer exposure times (24 h, 30 h). Our
      results suggest an inhibitory effect of MF on the G1-phase induced by altered
      expression of p16INK4a and p21CIP1.

PMID- 12201057
TI  - Post-translational modification of I-kappa B alpha activates NF-kappa B in human
      monocytes exposed to 56Fe ions.
AB  - The objective of this study was to investigate whether heavy ion (56Fe) radiation
      exposure activates one of the key transcriptional regulators, nuclear factor
      kappa B (NF-kappa B), in normal human monocytes (Mono Mac 6 cells: MM6). The
      study revealed that the exposure of MM6 cells to 56Fe ions resulted in increased
      NF-kappa B DNA-binding activity. The activation was both dose- and time
      dependent, with a maximum response at the 2 h time point after a 0.7 Gy dose.
      Cells pre-incubated with inhibitors of the phosphorylation and proteasome
      signaling pathway, completely blocked heavy ion-induced activation of NF-kappa B.
      These results clearly indicate that 56Fe ions can induce NF-kappa B DNA-binding
      activity in normal human monocytes, that the activation is rapid and persistent,
      and that the heavy ion-induced activation of NF-kappa B is mediated through
      phosphorylation of I-kappa B alpha and the subsequent proteasome-dependent
      degradation pathway. Since activation of NF-kappa B by extracellular stimuli is
      implicated in inflammation, infection and cancer induction, as well as in
      protection of cells against insult, it will be important in subsequent studies to
      elucidate whether heavy ion-induced NF-kappa B activation is involved in
      downstream gene expression.

PMID- 12201058
TI  - Radiation sensitivity of N. pharaonis in comparison with E. coli K12 strains.
AB  - To investigate the radiation sensitivity of the natronobacterium Natronomonas
      pharaonis in comparison with Escherichia coli strains (N. pharaonis DSM 2160T, E.
      coli strains AB1157 and K12 lambda s) were exposed to gamma-radiation (60Co-gamma
      source, 100 Gy min-1) in the presence of oxygen (air) and under strongly reduced
      oxygen conditions (argon-saturated medium). After irradiation, the colony-forming
      ability (dose-survival curves) and the D37 dose were determined. The oxygen
      content of the solutions containing high NaCl concentrations was measured with an
      oxygen electrode (Clark electrode). It was found that N. pharaonis can tolerate a
      remarkably higher irradiation dose than the two E. coli strains (approx. 1.5-fold
      of K12 lambda s and approx. 4-fold of AB1157). The oxygen enhancement ratio (OER)
      is 2.8 for N. pharaonis and 2.6 for both E. coli strains. Therefore the higher
      radiation resistance of the N. pharaonis is not due to the low oxygen content of
      the cell solution (high salt concentration) but is probably related to the higher
      DNA repair ability of this archaebacteria strain.

PMID- 12201059
TI  - Rejoining of DNA strand breaks by T4 DNA ligase in mammalian cells.
AB  - We have tested the ability of T4 DNA ligase to rejoin radiation-induced DNA
      strand breaks in living hamster cells (CHO-K1, EM9, xrs-5). T4 DNA ligase was
      introduced into cells by electroporation prior to x-irradiation. Single- and
      double-strand breaks were measured by the alkaline comet assay technique, and
      double-strand breaks (DSBs) were evaluated by the pulsed-field gel
      electrophoresis method. In the comet assay, the three cell lines showed reduced
      tail moments following pretreatment with T4 DNA ligase, both directly after
      irradiation and after repair incubation for 4 h. Similarly, the results obtained
      from pulsed-field gel electrophoresis showed reduced DSB frequencies after
      pretreatment with T4 DNA ligase. We conclude that exogeneous T4 ligase
      contributes to rejoining of radiation-induced strand breaks.

PMID- 12201060
TI  - p53-independent apoptosis in UV-irradiated mouse skin: possible inhibition by 50
      Hz magnetic fields.
AB  - Our recent results suggest that 50 Hz magnetic fields (MF) enhance ultraviolet
      (UV)-induced tumorigenesis in mouse skin. The aim of the present experiment was
      to study suppression of apoptosis as a possible mechanism for MF effects on skin
      tumorigenesis. Another aim was to test the importance of a UV and MF exposure
      schedule, particularly the role of MF exposure prior to UV irradiation. Female
      mice were exposed to a UV dose of 2 human MED and to 100 microT MF of 50 Hz,
      using the following exposure schedules: group 1 sham MF 24 h, UV 1 h, sham MF 24
      h; group 2 sham MF 24 h, UV 1 h, MF 24 h; group 3 MF 24 h, UV 1 h, MF 24 h. Lamps
      emitting simulated solar radiation (SSR) were used for UV irradiation. Skin
      samples were analysed for apoptosis, expression of the p53 gene, activity of the
      enzyme ornithine decarboxylase (ODC) and polyamine concentrations. A
      significantly (p = 0.017) lower number of apoptotic cells was measured in group 2
      compared to group 1. A similar but not statistically significant (p = 0.064)
      decrease was also detected in group 3. No p53 expression was detected in any
      sample. The levels of ODC and putrescine did not differ significantly between the
      UV-only and UV and MF-exposed groups. Spermidine and spermine levels were
      significantly (p = 0.014 and 0.014, respectively) lower in group 3 than in group
      1, but no decrease was observed in group 2. Our findings suggest that SSR induces
      p53-independent apoptosis in mouse skin and that the apoptotic response may be
      inhibited by exposure to MF. The exposure schedule did not alter the MF effect.
      The results do not support a causal role for polyamines in MF effects on
      apoptosis.

PMID- 12201061
TI  - The track structure of alpha-particles from the point of view of ionization
      cluster formation in "nanometric" volumes of nitrogen.
AB  - Probability distributions of the size of ion clusters created in "nanometric"
      volumes of nitrogen by single alpha-particles of a gold-plated 241Am source, were
      measured and compared with those calculated by Monte Carlo methods in the same
      geometry. The diameter of the sensitive volumes had a mass per area of between
      0.015 microgram/cm2 and 1.3 micrograms/cm2 which, for a material at unit density,
      corresponds to a nanometric target volume 0.15-13 nm in diameter. These nanometre
      sizes were simulated experimentally in a device called the Jet Counter. This
      consists of a pulse-operated valve which injects into an interaction chamber an
      expansion jet of molecular nitrogen gas, which is crossed by a narrow beam of
      alpha-particles. The resulting ions are counted and analyzed from the point of
      view of ionization cluster formation. The measured or calculated cluster size
      probabilities prove that the formation of ionization clusters along a "nanometre"
      track is governed by Poisson's law only in the case of very small target volumes,
      due to the contributions by secondary electrons. The present ionization cluster
      probabilities produced in "nanometric" volumes 0.15-13 nm in diameter, are the
      first ever determined experimentally and confirmed by Monte Carlo simulation.

PMID- 12201062
TI  - Traumatic deaths in Jamaica: a coroner's (medico-legal) autopsy study from the
      University Hospital of the West Indies.
AB  - This study reviewed the trauma-related deaths in a coroner's (medico-legal)
      autopsy series at the University Hospital of the West Indies and represents only
      the second such study reported from Jamaica. The autopsy protocols of all
      coroner's autopsies performed during the 15-year period January 1, 1983 to
      December 31, 1997 were reviewed retrospectively, and the clinico-pathological
      characteristics of trauma-related deaths were analysed. Trauma accounted for 470
      (28.7%) of the 1,640 coroner's autopsies and the causes of death in descending
      order of frequency were motor vehicle accidents [MVAs] (44.9%), blunt injuries
      (17.7%), burns (16.8%), firearm injuries (13.6%) and stab injuries (7.0%). The 21
      30 age group was the most commonly affected and the overall male: female ratio
      was 4:1. The distribution of injuries (excluding burns) by anatomical region was
      head and neck (43.8%), chest (8.9%), abdomen and pelvis (4.3%), extremities
      (0.9%) and multiple sites (25.3%). Forty-nine (23.2%) of the victims of MVAs were
      documented to have been pedestrians. Blunt trauma was most commonly due to
      accidental falls followed by assaults. Flame burns accounted for 90% of burn
      cases. There were seven (1.5%) cases of suicide overall. In this series the
      majority of trauma-related deaths occurred in young males and were due to MVAs.
      Strategies aimed at reducing trauma-related mortality should therefore emphasize
      road traffic safety programmes, particularly targeting the young.

PMID- 12201063
TI  - Implications of the Mental Health Act 1983 (Remedial) Order 2001.

PMID- 12201064
TI  - Study on the specificity of fibronectin for post-mortem diagnosis of early
      myocardial infarction.
AB  - In order to investigate the specificity of fibronectin (Fn) in the post-mortem
      diagnosis of myocardial infarction, the changes of Fn staining in normal,
      infarcted and other non-infarcted myocardial injuries resulting from myocarditis,
      mechanical asphyxia, electrocution, hemorrhagic shock, cardiac contusion and
      organophosphate poisoning were studied with an immunohistochemistry and image
      analysis system. The results showed that positive Fn staining could only be
      observed in groups of myocardial infarction and myocarditis, but could not be
      found in groups of mechanical asphyxia, electrocution, hemorrhagic shock, cardiac
      contusion, and organophosphate poisoning. Our findings indicate that positive
      staining of Fn in cardiomyocytes could be affected only by myocarditis, so it is
      quite specific for the diagnosis of myocardial infarction.

PMID- 12201065
TI  - The use of experts in medical malpractice litigation in Japan.
AB  - In medical malpractice litigation, the cooperation of medical experts is
      important. However, the appointment of experts has become problematic in Japan,
      apparently because many medical experts refuse to act in this capacity. However,
      this supposition has not until now been supported by quantitative evidence, since
      the fact that so few judgments in Japan are published made it impossible to
      investigate the situation. Therefore, we aim to show the state of the use of
      experts in medical malpractice litigation using objective data. Over the last ten
      years, the rate of the use of experts has averaged only 22.5%, varying according
      to region. Experts were used in 24.5% of cases involving an attorney on the
      patient's side, and in only 3.4% of cases where no attorney was used. The success
      rate of patients was higher when experts were adopted (39.1%) than when they were
      not (29.9%). The length of litigation involving experts was 4.0 years, and 2.7
      years when no expert was involved. This research suggested the necessity of
      establishing a formal cooperation system as soon as possible in Japan with no
      regional maldistribution.

PMID- 12201066
TI  - Evaluating alleged drinking after driving--the hip-flask defence. Part 1. Double
      blood samples and urine-to-blood alcohol relationship.
AB  - This two-part article examines the strengths and weaknesses of various ways of
      investigating claims of drinking alcohol after driving, commonly known as the hip
      flask or glove-compartment defence. In many countries the onus of proof in hip
      flask cases rests on the prosecution. With good co-operation from the police and
      timely sampling of body fluids, such as blood and urine for forensic analysis of
      ethanol, useful evidence can be mustered to support or challenge the truthfulness
      of alleged drinking after driving. The person's blood-alcohol concentration (BAC)
      can be compared with values expected on the basis of the amount of alcohol
      consumed after driving, according to theoretical Widmark calculations. The actual
      BAC measured is then adjusted for the additional amount of alcohol consumed in
      the after-drink. Double blood samples, that is, taking two specimens of venous
      blood about 30-60 minutes apart and looking at the magnitude and direction of
      change in BAC provides little or no more information than a single blood
      specimen. However, the relationship between alcohol in blood and urine is very
      useful in hip-flask cases whereby the concentration expected in the primary urine
      is compared with the concentration in the bladder urine voided. The concentration
      of alcohol determined in a second urine sample collected 30-60 min later gives
      supporting evidence in hip-flask cases. A graphical method, which entails
      plotting ethanol concentrations in blood and urine as a function of time provides
      a robust and practical way to investigate hip-flask defences. In the second part
      of the review, congener analysis is presented, which entails comparing the
      concentrations of n-propanol, isobutanol and occasionally other congeners in the
      alcoholic beverage allegedly consumed after driving with the volatiles present in
      the suspect's blood and urine determined by headspace gas chromatography.

PMID- 12201067
TI  - Sudden adult death: a medico-legal series of 77 cases between 1995 and 2000.
AB  - Among all the autopsies performed between 1995 and 2000 in our Department, 77
      adult cases of sudden death were selected. Sex, age, place of death,
      circumstances of death, causes of death and heart weight were reported from these
      77 post-mortem records. A complete forensic autopsy was performed in every case.
      Sudden death occurred more frequently in males at rest. Strenuous activity was
      rarely involved in sudden death and 72.7% of the cases died from cardiovascular
      disease, mainly coronary atherosclerosis. Non-cardiac causes were dominated by
      pulmonary and neurological diseases. Cardiomegaly was a frequent finding in cases
      who died from cardiac pathology. This study underlines the importance of complete
      medico-legal investigations in case of sudden death. Multiple heart samples are
      required in order to detect focal microscopic lesions, such as myocarditis and
      some forms of cardiomyopathy with minimal gross abnormalities. The post-mortem
      diagnosis of such cardiomyopathies is very important because the family of the
      deceased may undergo a possible screening. Toxicology is useful in the diagnosis
      of epileptic seizure and in identifying drugs like metamphetamine as a risk
      factor for some lethal cardiovascular pathologies such as aortic dissection.
      Molecular biology can also be helpful when limits of morphological diagnosis have
      been reached.

PMID- 12201068
TI  - Incipient Alzheimer's disease as the underlying cause of a motor vehicle crash.
AB  - A 75-year-old female driver died in a single vehicle crash. A forensic autopsy
      diagnosed the cause of death as blood loss due to laceration of the liver caused
      by the crash. Although she had neither clinical history of dementia nor gross
      abnormalities of the brain, neuropathological examinations showed a substantial
      number of senile plaques indicative of Alzheimer's disease (AD). An interview
      with a family member revealed that she had symptoms of dementia. Cognitive
      dysfunction due to AD was proposed as the underlying cause of the crash. It is
      recommended that forensic autopsy of older drivers should include
      neuropathological examinations to identify incipient AD. Recognition of AD as an
      underlying cause of crashes is also important to promote the health care of older
      people.

PMID- 12201069
TI  - Case history of co-morbid Asperger's syndrome and paraphilic behaviour.
AB  - We report a case of a man with Asperger's syndrome, paraphilic behaviour and
      convictions for sexual offences. We describe his assessment within a secure
      mental health setting to determine issues of diagnosis, treatment and risk. We
      also highlight the difficulty in reducing the risk of further offending because
      of the apparent ineffectiveness of interventions for the small group with
      Asperger's syndrome and an offending history. Consequently, they are likely to
      face long periods in institutional settings.

PMID- 12201070
TI  - The National Survey of Psychiatric Morbidity among prisoners and the future of
      prison healthcare.
AB  - It has long been known that psychiatric disorders are highly prevalent among
      prisoners (Coid, 1984; Gunn et al., 1991; Maden et al., 1995; Joukamaa, 1995;
      Bland et al., 1998; Lamb and Weinberger, 1998). However, the Survey of
      Psychiatric Morbidity Among Prisoners in England and Wales (Singleton et al.,
      1998) represents a considerable advance on earlier surveys. By using the same
      standardized psychiatric assessment procedures, and similar questions on
      medication, service use and social functioning, its findings can be compared with
      previous national surveys of adults living in private households (Meltzer et al.,
      1995), residents in institutions (Meltzer et al., 1996), homeless persons (Gill
      et al., 1996), and with the forthcoming household survey in England, Wales and
      Scotland. It should also inform the future organisation of healthcare for
      prisoners, following recent recommendations from a joint Home Office/Department
      of Health Working Party that Health Authorities must work with prisons in their
      catchment areas to carry out joint health needs assessments, agree prison
      healthcare improvement strategies and jointly plan and commission services (HM
      Prison Service and NHS Executive 1999). The ultimate test of the survey will be
      whether it provides a benchmark to evaluate the future effectiveness of the new
      policy changes.

PMID- 12201071
TI  - Poisoning in northern India: changing trends, causes and prevention thereof.
AB  - A twenty-one years retrospective study (1980-2000) of acute poisoning deaths
      carried out at the Department of Forensic Medicine and Toxicology at Government
      Medical College Hospital, Jammu and Gov't. Medical College Hospital, Chandigarh-
      the two demographically different zones of Northern India. Union Territory of
      Chandigarh, which is the capital of Punjab and Haryana states, is one of the most
      developed parts of India, whereas Jammu primarily represents the rural India. The
      study is an attempt to analyze the various changing trends in acute poisoning in
      these zones with the aim that it will help immensely the health policy-makers to
      equip health care institutions accordingly. The present study reveals a steep
      increase in the number of acute poisoning cases and a change in the trends of the
      most commonly used poisons with the passage of time. Males outnumbered females
      and youth formed the majority of fatalities. The main victims were unemployed
      youth and students, followed by agricultural and domestic workers. Despite
      India's predominantly rural character, the urban preponderance of deaths by
      poisoning may reflect the role of leading a more stressful life in urban areas.

PMID- 12201072
TI  - Wrongful birth claim in Japan.
AB  - Wrongful birth claim is generally defined as a claim by the parents of a child
      born alive but with a disability that a doctor was negligent in permitting the
      pregnancy to continue to birth. There have been four cases relating to congenital
      rubella syndrome and one case relating to Down's syndrome held in Japan. The
      claims brought by the mothers were that, but for the negligence of the doctor in
      managing the pregnancy, the mother would have had a lawful abortion and the child
      would not have been born to suffer a disability. As we do not have the provision
      of foetal indication for abortion in Japan, wrongful birth claim by parents is
      founded upon a breach of doctors' duty in advising of the probability of a
      disabled child. We compare the lawful nature of wrongful birth claims in Japan
      with those in the United States and the United Kingdom.

PMID- 12201073
TI  - A curious autopsy case of a car crash in which self-strangulation and lung
      collapse were found: a case report.
AB  - A curious autopsy case following the car crash of a 20-year-old male, in which
      self-strangulation and lung collapse were observed, is presented. His motor
      vehicle had crashed into a restaurant as a result of self-strangulation using an
      electrical cord wound four times around his neck. At autopsy, we found small
      rupture holes of spontaneous bullae in both lung apices, which had probably taken
      place upon collision during driving, petechial hemorrhages in the face skin and
      the absence of severe injuries. Since it seemed unlikely that the small holes in
      both lung apices caused fatal pneumothorax instantly, the cause of his death was
      judged to be asphyxia due to self-strangulation. It is not clear whether the self
      strangulation was suicidal or autoerotic, because neither traces of suicidal
      intent nor circumstances suggesting either of them were disclosed.

PMID- 12201074
TI  - Report of a suicidal digoxin intoxication: a case report.
AB  - Digoxin is a cardiotonic glycoside that is primarily used in the treatment of
      heart failure, atrial fibrillation or flutter, and paroxysmal atrial tachycardia.
      Intoxication due to digitalis excess is a common problem in clinical practice
      because it is therapeutically effective within a narrow dose range. However,
      massive intoxication with digitalis glycosides following a suicidal attempt is a
      rare event. In this report we describe an overdose fatality involving digoxin in
      a suicidal 82-year-old man, in whom measurement of serum digoxin concentration is
      available. A toxicological study of our patient, approximately two and a half
      hours after ingestion of the drug, revealed digoxin concentrations within 12.2
      13.2 ng/ml in the blood, while the mean therapeutic serum concentration ranged
      from 0.5 to 2 ng/ml.

PMID- 12201075
TI  - Post-mortem castration by a dog: a case report.
AB  - A man was found dead in a room where two dogs and a cat were wandering freely.
      His legs were bare and his underpants presented a few small tears. The deceased
      exhibited a partial emasculation but with only a small amount of bleeding. No
      other significant injuries were found, particularly no defence lesions. Death was
      natural, caused by the rupture of a myocardial infarct. A small piece of
      connective tissue was found in the gastric contents of one of the dogs. This
      fragment, as well as bloodstained hairs from its jaws, were analysed for DNA.

PMID- 12201076
TI  - Seclusion of women patients at the hospital.

PMID- 12201077
TI  - Introduction. Modulite: simplifying the changeover.

PMID- 12201078
TI  - Clinical studies in asthmatics with a new non-extra fine HFA formulation of
      beclometasone dipropionate (BDP Modulite).
AB  - The main objective of the clinical development programme for BDP Modulite, a new
      non-extra fine formulation of beclometasone dipropionate (BDP) in
      hydrofluoroalkane (HFA), has been to demonstrate therapeutic equivalence compared
      with standard BDP chlorofluorocarbon (CFC) products at the recommended posology
      (delivered dose and patient population). A total of 1158 asthmatic patients were
      included in five clinical studies and 658 patients were treated with BDP
      Modulite. Four studies were undertaken in mild or moderate-to-severe asthmatic
      adults, while one study was carried out in children. The duration of treatment
      was 12 weeks in three studies and 6 weeks in the other two studies. A range of
      doses of BDP Modulite from 200 micrograms bid up to 1500 micrograms bid was
      evaluated against CFC comparators. The primary efficacy variable in all studies
      was morning PEFR while secondary variables included other lung function
      parameters, symptom scores and salbutamol use. All studies demonstrated
      equivalence of efficacy for morning PEFR for BDP Modulite versus BDP-CFC when
      compared on a microgram for microgram basis. The secondary outcome variables also
      consistently support similar efficacy of the two products. The safety and
      tolerability profile for BDP Modulite was similar to BDP-CFC; the incidence of
      adverse events was comparable between treatments and plasma and urinary cortisol
      were generally unchanged in patients receiving 1000 micrograms day-1 for 6-12
      weeks. In conclusion, the results of the clinical studies with BDP Modulite show
      that this new HFA formulation allows a seamless transition to CFC-free BDP, thus
      simplifying the changeover.

PMID- 12201079
TI  - Modulite: a means of designing the aerosols generated by pressurized metered dose
      inhalers.
AB  - Although popular, the pressurized metered dose inhaler generates coarse, fast
      moving clouds so that the fraction reaching the lung is small. These shortcomings
      can be redressed by Modulite which permutes the following variables: the non
      volatile components of a solution formula, the actuator orifice geometry, the
      volume of the metered solution and the vapour pressure of the propellants. This
      permits the design of aerosols with chosen particle size and plume speed. This
      facilitates co-ordination of dose generation with inspiration, reduces
      oropharyngeal deposition and provides a mechanism for targeting drug delivery to
      different parts of the lung. These principles are exemplified by designing an HFA
      propelled beclometasone dipropionate product which closely matches existing
      products which use chlorofluorocarbons.

PMID- 12201081
TI  - War is bad for health.

PMID- 12201080
TI  - Modulite technology: pharmacodynamic and pharmacokinetic implications.
AB  - In the drive to replace chlorofluorinated hydrocarbons (CFCs) by alternative more
      environmentally friendly propellants in pressurized metered dose inhalers
      (pMDIs), Chiesi has developed new inhalers using Modulite technology. The aim was
      to obtain CFC-free pMDIs which are equivalent, in terms of safety and efficacy,
      to the previous CFC devices at the same dose. When beclometasone dipropionate
      (BDP) and budesonide Modulite formulations were compared to the equivalent CFC
      products there was no significant difference in morning serum cortisol or urinary
      cortisol excretion, at the maximum recommended daily dose (2000 micrograms or
      1600 micrograms respectively). Single dose pharmacokinetic studies in both
      healthy volunteers and asthmatic patients compared systemic exposure (B17MP
      levels) for BDP-CFC with BDP Modulite and extrafine BDP-HFA (QVAR). B17MP levels
      for BDP-CFC and BDP Modulite were comparable, but substantially less than that
      seen with extrafine BDP-HFA. After 6 weeks of treatment in asthmatic patients,
      B17MP AUC after inhalation of BDP (1000 micrograms twice-daily) from BDP Modulite
      was comparable with that obtained after BDP-CFC (Becloforte). Plasma profile of
      BDP and B17MP were similar after inhalation from BDP Modulite with standard
      actuator or delivered via a spacer, suggesting that pulmonary delivery of BDP to
      the lung is similar with both actuators.

PMID- 12201082
TI  - The impact of the intifada on the health of a nation.
AB  - This article describes the nature and extent of non-fatal injuries sustained by
      Palestinians during the first three months of the second intifada in late 2000 by
      looking at two sets of data. 10,279 cases were obtained from the records of the
      Red Crescent Organization, which provides first level emergency care via
      ambulance crews in the West Bank and Gaza Strip. For 6,071 cases in the West
      Bank, additional information was available from the Ministry of Health, which
      keeps records of first and second emergency level care provided at hospitals and
      health points. The Ministry of Health cases were classified by type of weapon,
      site of injury and level of treatment provided. Fifty-eight per cent of injuries
      occurred in young men 18-34 years, but 25 per cent occurred in school children,
      ten per cent in people over 50 years and five per cent in females. Fifty-nine per
      cent of the injuries were caused by bullets and 76 per cent of these affected the
      upper part of the body; 13.4 per cent of the injuries were severe, with major
      implication for disability and the need for long-term care and support.

PMID- 12201083
TI  - Healthcare under sanctions in Iraq: an elective experience.
AB  - As a consequence of the 1991 Gulf War and the ensuing UN sanctions, not only was
      the Iraqi government destroyed, but also the general infrastructure of the
      country was disrupted, with the civilian population and public services bearing
      much of the aftermath. Ten years after the war, the health system in Iraq is
      still in a perilous situation. The effects of sanctions have affected almost
      every aspect of medical care. There has been a mass exodus of health care
      professionals, many of whom were foreign nationals. Doctors' salaries fell
      rapidly to only $30 a month, barely enough to buy the necessities of daily
      living. Iraqi hospitals have no access to foreign journals, textbooks or the
      internet; leading to a generation of out-dated and under-skilled health
      professionals. Most worrying is the ever-present embargo on many essential
      medicines. Only one-third of the medicines are available for chemotherapy for the
      treatment of acute lymphoblastic leukaemia in children (UKALL 97 modified 99
      protocol). At the Al-Mansour paediatric teaching hospital this shortfall has led
      to a substantial increase in childhood mortality, with disease-free survival
      rates falling to 25 per cent compared to 60 per cent in 1988.

PMID- 12201084
TI  - Obstetrics during Civil War: six months on a maternity ward in Mallavi, northern
      Sri Lanka.
AB  - A long-term, large-scale ethnic armed conflict continues in Sri Lanka, where
      militant separatists control a northern section of the island. The conflict has
      resulted in a large population of internally displaced persons and a shortage of
      medical staff. Drug and equipment shortages compound the difficulty in access to
      medical care. This article reports the experiences from 1 November 2000 to 30
      April 2001 recorded by review of medical records and by interviews, in the
      peripheral unit, in a separatist controlled area of the Mallavi maternity ward.
      There were 704 births. Most of the mothers had been displaced by the war (69.5
      per cent) and had experienced food shortage (67.5 per cent). Referred patients
      (18.1 per cent) had a high rate of caesarean section (44.3 per cent) and had
      travelled a mean of 57.6 km to reach Mallavi. There had been substantial
      antenatal care (94.0 per cent), tetanus toxoid vaccination (95.1 per cent) and
      malaria prophylaxis (86.4 per cent). Risk factors for low birth weight included a
      maternal body mass index less than 19 (RR 1.55, CI 1.11-2.16, P = .011),
      primiparity (RR 1.44, CI 1.05-1.97, P = .024) and self-reported malarial
      infection during pregnancy (RR 1.42, CI 1.03-1.97, P = .036). Rates of low birth
      weight, stillbirths, neonatal deaths and maternal mortality in the Mallavi units
      were higher than the Sri Lankan national averages. Improvements in quality of
      care and access to health care are unlikely while the war continues.

PMID- 12201085
TI  - A short history of biological warfare.
AB  - Biological weapons have been used in war from the start of recorded history. This
      article reviews the history of the subject, including the outbreak of the Black
      Death and the use of smallpox against American Indians. The new science of
      microbiology was misused from soon after its start and, despite the 1925 Geneva
      Protocol, the Japanese experimented extensively on prisoners in China. The Allies
      carried out extensive research during the Second World War, notably the United
      Kingdom into anthrax on Gruinard Island and the United States into a variety of
      agents. Despite the 1972 Biological Weapons Convention (BWC), a major programme
      continued in the former Soviet Union (leading to an accidental outbreak of
      anthrax). Most recently Iraq was revealed as having an extensive programme, with
      weaponization of large amounts of various agents, and several terrorists groups
      have attempted to use biological agents as weapons. Modern developments in
      biotechnology could lead to even more serious developments, and effective
      preventive measures, including strengthening of the BWC, are imperative.

PMID- 12201086
TI  - Progress in the international protection of human rights.
AB  - Great progress has been made in the international protection of human rights
      since 10 December 1948 (when the United Nations General Assembly adopted the
      Universal Declaration of Human Rights). Amidst the doom and gloom of the media's
      reporting of current affairs, it is easy to overlook this progress. This article
      provides a definition of 'human rights' and examines early human rights
      campaigns. It then considers the areas of progress: human rights are now part of
      the international political vocabulary, there is a recognition that respect for
      human rights can assist a country's economic and social development, there has
      been a growth of human rights treaties and techniques and non-governmental
      organizations (NGOs) see protecting human rights as a major activity. State
      sovereignty has been eroded as national governments are being held accountable to
      the international community for their human rights policies. A new challenge is
      to ensure respect for human rights by non-state entities, such as transnational
      corporations. The growing culture of international protection of human rights is
      here to stay. This is not a reason for complacency, but it is a sign of hope.

PMID- 12201087
TI  - Project Sunshine and the slippery slope: the ethics of tissue sampling for
      strontium-90.
AB  - When citizens of Atlantic alliance countries are being asked by their elected
      leaders to suspend many of the fundamental rights of democracy in order to defend
      them, it is timely to consider the perils of the slippery slope that was opened
      up by the harvesting of human bones and tissue for studies of strontium-90
      fallout during the height of the cold war. In particular, the need to collect
      samples from recently deceased infants and children seems to have overridden the
      rights of parents to determine what became of their loved ones after death. Forty
      years later, parents and others question whether the fact that this research
      contributed significantly to the partial moratorium on atmospheric tests
      justified the overriding of their rights. It also reminds us that the testing of
      nuclear devices, even in the defence of democracy, presents global health
      hazards.

PMID- 12201088
TI  - Blood money: the duty of care to veterans of UK nuclear weapons tests.
AB  - Fifty years after the first UK nuclear weapon test at Monte Bello off the north
      west coast of Australia in October 1952, this article documents the deliberate
      and repeated decisions not to provide adequate radiation protection to most of
      the 40,000 men who participated in the British programme in the 1950s in
      Australia and Christmas Island, precisely to avoid future liability claims. The
      evidence lies in the minutes and memoranda of the scientists, doctors and
      military leaders overseeing these tests. Archival material in the United Kingdom
      Public Records Office and the National Archives of Australia is, according to
      senior barristers, sufficient to sustain an allegation of negligence, even by the
      standards of 50 years ago, against the government of the day and an allegation of
      cover-up by the current government, faced with potentially huge compensation
      bills and pension pay-outs for long-term radiation injury to former servicemen.
      Recent governments have tried to reassure the veterans with epidemiological
      studies, which are almost inevitably inconclusive. However, pilot studies have
      now begun on radiobiological tests that may be able to determine whether a
      particular individual was irradiated significantly 40 or 50 years ago and whether
      he has subsequently suffered cancers or other ill health because of this
      radiation burden. The first results from these studies should be available around
      the time of the fiftieth anniversary of the first UK test.

PMID- 12201089
TI  - Appropriate basis of effluent standards for industrial wastewaters.
AB  - Designing industrial discharge standards should reflect the numerical compromise
      between what can be achieved to prevent environmental pollution and sustainable
      development. They should involve categorical limitations for specific sources.
      Micropollutants represent the major concern for industrial effluents. A
      micropollutant-based subcategorization is needed for an effective control of
      industrial effluents. Regulations imposed require a comprehensive knowledge of
      polluting processes and sources, and technological limits of available treatment
      technologies.

PMID- 12201090
TI  - Field test of methane fermentation system for treating swine wastes.
AB  - A methane fermentation system for treating swine wastes was developed and
      successfully demonstrated in a field test plant (0.5 m3/d). The system was
      composed of a screw-press dehydrator, a methanogenic digester, a sludge
      separator, an oxidation ditch (OD) and composting equipment. A performance
      evaluation was carried out regarding physical pre-treatment using the screw-press
      dehydrator, methane fermentation for pre-treated slurry, and post-treatment for
      digested effluent by OD. Total solids (TS) and chemical oxygen demand (CODCr)
      removal by the screw-press pre-treatment were 38% and 22%, respectively.
      Properties of the screenings were as follows: water content 57%, ignition loss
      93%, specific gravity 0.33. The pretreated strong slurry was digested under
      mesophilic conditions. Digestion gas (biogas) production rate was 25 m3/m3-slurry
      (NTP) and methane content of the biogas was 67%. CODCr removal of 65% with
      methane fermentation treatment of the slurry operating at 35 degrees C was
      observed. No inhibition of methane fermentation reaction occurred at the NH4(+)-N
      concentration of 3,000 mg/l or less during methane fermentation by the system.
      Mass balance from the present pilot-scale study showed that 1 m3 of mixture of
      excrement and urine of swine waste (TS 90 kg/m3) was biologically converted to 25
      m3/m3-slurry (NTP) of biogas (methane content 67%), 100 kg of compost (water
      content 40%, ignition loss 75%), and 0.80 m3 of treated water (SS 30-70 mg/l).

PMID- 12201091
TI  - Anaerobic digestion of organic waste in Japan: the first demonstration plant at
      Kyoto City.
AB  - Recycling of Municipal Solid Waste is vigorously promoted in Japan and the
      necessity of energy recovery from organic waste is increasing. An anaerobic
      digestion demonstration plant for organic waste in Kyoto City, Japan has been
      operated for about two years. Three kinds of wastes (garbage and leftovers from
      hotels, yard waste and used paper) mixed at various ratios are used. The plant
      has maintained stable operations with each mixture, generating biogas by the
      decomposition of VS at the rate of about 820 m3N/ton-VS.

PMID- 12201092
TI  - PHA (polyhydroxyalkanoate) production potential of activated sludge treating
      wastewater.
AB  - The main purposes of wastewater treatment systems are to remove organic
      pollutants, but it would be very attractive if there were a way to recover the
      organic pollutants as valuable organic materials. One of the possible ways to
      recover organic pollutants in wastewater is to convert them into
      polyhydroxyalkanoates (PHAs), which are biodegradable plastics. In this study, 18
      activated sludge samples in 4 wastewater treatment plants (WWTPs) in Tokyo,
      Japan, were evaluated for their potential to produce PHAs by aerobic batch
      experiments with excess supply of acetate as the sole carbon source. The
      activated sludge samples tested had the capability to accumulate PHA up to 18.8%
      of dry cell weight on average, with the range of 6.0% to 29.5%. The results
      showed that the maximum PHA content was dependent on the influent more than on
      the operational conditions of the activated sludge, and that conventional
      activated sludge produced PHA as much as anaerobic-aerobic activated sludge did.
      The PHA content achieved in this study is still low, and further improvement is
      needed to put into practice the recovery process of organic pollutants as
      biodegradable plastics by activated sludge.

PMID- 12201093
TI  - A strategy in wastewater treatment process for significant reduction of excess
      sludge production.
AB  - A novel wastewater treatment process (S-TE PROCESS) with significantly reduced
      production of excess sludge has been developed. The process consists of two
      different stages, one for a biological wastewater treatment and the other for a
      thermophilic aerobic digestion of the resulting sludge. A portion of return
      sludge from the wastewater treatment step is injected into a thermophilic aerobic
      sludge digester (TASD), in which the injected sludge is solubilized by the action
      of thermophilic aerobic bacteria. The solubilized sludge is returned to the
      aeration tank in the wastewater treatment step for its further degradation. Pilot
      scale facilities of the S-TE process and the conventional activated sludge
      process as a control, both treating the same industrial wastewater, were
      comparatively operated for totally 270 days. As a result, 93% reduction in
      overall excess sludge production was achieved in the S-TE operation. The SS
      solubilization rate in TASD was stable at around 30%. Only a slight increase in
      the effluent SS and TOC concentrations was observed compared with those of the
      control facility. Otherwise the removal efficiency of TOC was approximately 95%
      for both plants. A full-scale plant treating domestic sewage was operated for
      three years, showing 75% reduction of overall excess sludge production. It was
      concluded that the new process was feasible.

PMID- 12201094
TI  - Present state of food and feed cycle and accompanying issues around Japan.
AB  - Nitrogen (N) and phosphorus (P) cycles of food and feed, and the regulation
      systems for industrial wastewater are studied. The rate of domestic supply of
      food in Japan is 41% in 1970, 32% in 1990, and 29% in 1998 for N and 33%, 29%,
      and 28% for P, excluding grass feed. Among 3 countries, Japan, USA and Thailand,
      Japan is in the most difficult state to recycle food wastes to farmland.
      Comparing the estimated load of wastewater from food processing industries with
      the estimated load according to the budget study for N and P cycles, the
      tentative criteria of wastewater of food processing for P seem to be loose, and
      denitrification might be considered in every stage of N cycles. New regulation of
      industrial wastewater recently proposed in Japan may induce the chance for
      environmental business to remove N and P.

PMID- 12201095
TI  - Toxicity assessment on combined biological treatment of pharmaceutical industry
      effluents.
AB  - This paper describes the wastewater characterization and aerobic/anaerobic
      treatability (oxygen uptake rate and biogas production measurement) of chemical
      synthesis based pharmaceutical industry effluents in a nearby baker's yeast
      industry treatment plant. Preliminary experiments by the industry had indicated
      strong anaerobic toxicity. On the other hand, aerobic treatability was also
      uncertain due to complexity and unknown composition of the wastewater. The work
      in this study has indicated that the effluents of the pharmaceutical industry can
      be treated without toxicity in the aerobic stage of the treatment plant.
      Methanogenic activity tests with anaerobic sludge from the anaerobic treatment
      stage of the wastewater treatment plant and acetate as substrate have confirmed
      the strong toxicity, while showing that 30 min aeration or coagulation with an
      alum dose of 300 mg/l is sufficient for reducing the toxicity almost completely.
      Powdered activated carbon, lime and ferric chloride (100-1,000 mg/l) had no
      effect on reduction of the toxicity. Consequently, the pharmaceutical industry
      was recommended to treat its effluents in the anaerobic stage of the nearby
      baker's yeast industry wastewater treatment plan at which there will be no VOC
      emission and toxicity problem, provided that pretreatment is done.

PMID- 12201096
TI  - High-rate methane fermentation of lipid-rich food wastes by a high-solids co
      digestion process.
AB  - This paper presents an experimental study on anaerobic degradation of lipids-rich
      food wastes by using the high solids co-digestion process. The experiments were
      conducted under mesophilic (35 degrees C) and thermophilic (55 degrees C)
      condition, respectively, by using a semi-continuous flow completely mixed
      reactor. The influent TS level was controlled at around 10%, while the hydraulic
      retention time (HRT) was changed from 15 days to 7.5 days. The lipids (fats or
      oil and grease) content in the influent TS was changed from 8% to 40% by adding
      salad oil (vegetable) and lard (animal) to the food wastes. The result of this
      study showed that the food wastes containing high lipids content was effectively
      degraded by the high solids co-digestion process and over 85% of lipid was
      degraded to biogas with 60-65% of methane. In addition, thermophilic methane
      fermentation was more effective for reducing lipids and had more higher loading
      capacity compared with mesophilic condition.

PMID- 12201097
TI  - Algal treatment of pulp and paper industry wastewaters in SBR systems.
AB  - Highly colored and highly polluted pulp and paper industry wastewaters are
      proposed to be treated by using algae in sequential batch reactors (SBR). Results
      of batch studies revealed that up to 74% COD; 74% color removal could be attained
      in about 40 days of incubation. From the preliminary SBR experiments, filling
      period was found to be a critical step affecting the overall efficiency when
      mixing and aeration is applied during filling. Therefore, 5 different filling
      periods (4, 6, 8, 10 and 12 days) were studied with a total SBR cycle of 15 days.
      For all filling periods; COD, color and AOX removal efficiencies increased with
      increasing filling time. Maximum removal efficiencies achieved were 60 to 85% for
      COD, 42 to 75% for color and 82 to 93% for AOX for the filling periods of 4 to 12
      days. For 8 days or longer filling periods, no additional reaction time was
      required. Results showed that, organics in the wastewater were both chlorinated
      and non-chlorinated; algae removed these mainly by metabolism; and chlorine
      cleavage from chlorinated organic molecules was more rapid than the degradation
      of non-chlorinated and colored organics. Adsorbed lignin on algal biomass was
      found to be varying between 10-20% depending on filling period applied.

PMID- 12201098
TI  - A hybrid two-phase system for anaerobic digestion of food waste.
AB  - A hybrid two-phase system, consisting of a solid waste reactor as the
      acidification reactor and a wastewater reactor, i.e. an upflow anaerobic sludge
      blanket (UASB) reactor, as the methanogenic reactor, for anaerobic digestion of
      food waste was investigated. After the pre-acidification stage, COD and total VFA
      removals in the methanogenic phase were in the ranges of 74-93% and 77-100%,
      respectively, while leachate COD and total VFA concentrations in the
      acidification phase decreased by 95% and 97-99%, respectively. Some 99% of the
      total CH4 generated was from the methanogenic phase with the CH4 content of 68
      70%. About 77-79% of TOC, 57-60% of volatile solids and 79-80% of total COD were
      removed. The results of this laboratory-scale study show that the hybrid two
      phase anaerobic batch reactor system is suitable for effective conversion of food
      waste into CH4 and CO2. The hybrid two-phase system can be further developed into
      an effective and efficient way to enhance waste stabilization in operating
      bioreactor landfills.

PMID- 12201099
TI  - Application of membrane-coupled anaerobic volatile fatty acids fermentor for
      dissolved organics recovery from coagulated raw sludge.
AB  - To investigate the treatment performance of membrane-coupled anaerobic volatile
      fatty acids fermentor system, the effects of operational parameters for volatile
      fatty acids production were evaluated through experiments and a mathematical
      model. The volatile fatty acids recovery ratio was largely affected by the change
      of hydraulic retention time, reaching its maximum value at 12 hrs. Over the range
      of hydraulic retention time 8 to 96 hrs, the volatile fatty acids recovery ratio
      decreased with the increase of hydraulic retention time above 12 hrs, while the
      ratio of mineralization and gasification increased. Hydraulic retention time and
      membrane filtration ratio should be maintained less than 1 day and above 0.9,
      respectively, to attain over 40% of organic materials recovery ratio at 10 days
      of solids retention time. When the hydrolysis rate constant was 0.01 hr-1, the
      organic loading rate should be maintained at above 1.0 (kgC/m3/day) to attain
      over 45% of volatile fatty acids recovery ratio. Based on experimental and
      simulated results, membrane-coupled anaerobic volatile fatty acids fermentor
      system was thought to be effective for dissolved organics recovery from
      coagulated sewage sludge.

PMID- 12201101
TI  - Effect of dissolved oxygen conditions on nitrogen removal in continuously fed
      intermittent-aeration process with two tanks.
AB  - In this study, an intermittent aeration type activated sludge process that is fed
      continuously is evaluated for nitrogen and organic carbon for facilities in rural
      areas, which are characterized by small scale, low loading rate and automatic
      operation. Anoxic and aerobic conditions can be regulated alternatively by
      intermittent aeration for biological nitrogen removal. It is proved that an
      intermittent aeration cycle of 90 min, with aeration/anoxic mixing periods of 25
      30 min/65-60 min in Tank 1, and 30-45 min/60-45 min in Tank 2, and a DO control
      set at 0.6-1 mg/L during the aeration period are required for satisfactory
      treatment performance. Under these conditions, a stable effluent water quality
      with BOD < or = 5 mg/L, CODMn < or = 8 mg/L, Nitrogen < or = 3 mgN/L, SS < or = 5
      mg/L and transparency > or = 80 cm can be achieved. The solids retention time in
      aerobic condition was 10-25 d, which is sufficient for nitrification.

PMID- 12201100
TI  - Isolation and characterization of the ethynylestradiol-biodegrading microorganism
      Fusarium proliferatum strain HNS-1.
AB  - We cultivated hundreds of sediment, soil, and manure samples taken from rivers
      and farms in a medium containing ethynylestradiol (EE2) as the sole source of
      carbon, so that microorganisms in the samples would acclimatize to the presence
      of EE2. Finally, we isolated an EE2-degrading microorganism, designated as strain
      HNS-1, from a cowshed sample. Based on its partial nucleotide sequence (563 bp)
      of the 28S rRNA gene, strain HNS-1 was identified as Fusarium proliferatum. Over
      15 days, F. proliferatum strain HNS-1 removed 97% of EE2 at an initial
      concentration of 25 mg.L-1, with a first-order rate constant of 0.6 d-1. Unknown
      products of EE2 degradation, which may be more polar compounds that have a
      phenolic group, remained in the culture medium.

PMID- 12201102
TI  - Ammonia recovery from high strength agro industry effluents.
AB  - The aim of the study was to investigate ammonia recovery from high strength agro
      industry effluents involving significant amounts of ammonia, by applying
      magnesium ammonium phosphate (MAP) precipitation technology. Two types of
      industrial effluents have been tested in the study. The first plant was an opium
      alkaloid processing industry and the second one was a baker's yeast industry.
      High chemical oxygen demand (COD), total Kjeldahl nitrogen (TKN) and unacceptable
      dark brown color characterized effluents from both industries. Effluents from the
      biologically treated opium alkaloid and baker's yeast industries were both
      applied at the stoichiometric ratio (Mg:NH4:PO4 = 1:1:1) and above the
      stoichiometric ratio (Mg:NH4:PO4 = 1.1:1:1.1) to MAP precipitation. NH4 removals
      of 61-80% were achieved at the pH of 9.2 at the stoichiometric ratio, whereas 83%
      NH4 removal was obtained at the pH of 9.2 above the stoichiometric ratio.
      Experimental studies performed on both anaerobically and/or aerobically treated
      baker's yeast and opium alkaloid industry effluents have clearly indicated that
      MAP precipitation was an appropriate treatment option for NH4 removal or struvite
      recovery from high ammonia content agro industry effluents. Additional ammonia
      recovery studies were conducted on ozonated and Fenton's oxidation applied
      effluents and these have also indicated that the amounts of struvite and the
      quality of MAP precipitate was increased significantly. In this framework, MAP
      sludge recovered from combined biological and Fenton's oxidation treatment
      effluents were considered as a more valuable slow release fertilizer for
      agricultural use.

PMID- 12201103
TI  - Nitrogen nutrient removals from wastewater and river water.
AB  - Elevated levels of nutrients in agroindustry wastewaters, and higher reliance on
      chlorination pose health threats due to formation of chlorinated organics as well
      as increased chlorination costs. Removals of ammonium and nitrate compounds were
      studied using activated carbon from palm shells, as adsorbent and support media.
      Experiments were carried out at several loadings, F:M from 0.31 to 0.58, and
      hydraulic residence times (HRT) of 24 h, 12 h and 8 h. Results show that the
      wastewater treatment process achieved removals of over 90% for COD and 62% for
      Total-N. Studies on removals from river water were carried out in sequencing
      batch reactor (SBR) and activated carbon biofilm (ACB) reactor. Removals achieved
      by the SBR adsorption-biodegradation combination were 67.0% for COD, 58.8% for
      NH3-N and 25.5% for NO3-N while for adsorption alone the removals were only 37.0%
      for COD, 35.2% for NH3-N and 13.8% for NO3-N. In the ACB reactor, at HRT of 1.5
      to 6 h, removals ranged from 12.5 to 100% for COD, 16.7 to 100% for NO3-N and
      13.5 to 100% for NH3-N. Significant decrease in removals was shown at lower HRT.
      The studies have shown that substantial removals of COD, NO3-N and NH3-N from
      both wastewater and river water may be achieved via adsorption-biodegradation by
      biofilm on activated carbon processes.

PMID- 12201104
TI  - Assessment of source-based nitrogen removal alternatives in leather tanning
      industry wastewater.
AB  - Nitrogen is an important parameter of leather tanning wastewaters. Magnesium
      ammonium phosphate (MAP) precipitation is a chemical treatment alternative for
      ammonia removal. In this study, a detailed source-based wastewater
      characterisation of a bovine leather tannery was made and nitrogen speciation as
      well as other basic pollutant parameter values was evaluated. This evaluation has
      led to definition of alternatives for source-based MAP treatment. MAP
      precipitation experiments conducted on these alternatives have yielded over 90%
      ammonia removal at pH 9.5 and using stoichiometric doses. Among the alternatives
      tested liming-deliming and bating-washing was found to be the most advantageous
      providing 71% ammonia removal.

PMID- 12201105
TI  - Effect of solution parameters on the removal efficiency of humic substances by a
      reuse material.
AB  - This paper provides an overview of the ability of polypropylene (PPL), a
      synthetic polymeric adsorbent made from reused plastic material. The removal of
      humic substances (HS) in a solution pretreated with
      dedoxyltrimethylammoniumbromide (DDTMAB), a cationic quaternary ammonium compound
      (QAC), was studied under various conditions. The removal of HS was achieved in
      its solute complexed form but also as suspended solids. The conditions of the HS
      solution, which fluctuation was suspected to have an impact on the performance of
      the adsorbent, were tested. The parameters investigated included the pH, the
      initial concentration of the surfactant, and the presence of suspended solids in
      solution. The results of the laboratory scale experiments showed that PPL removal
      efficiency of HS is strongly pH dependant with higher removal achieved at pH
      greater than 7. However, the shift for pH above 7 induced an increase in the
      optimum doses of DDTMAB as more and more deprotonated HS become available to
      react with DDTMAB. Ionic strength did have the opposite effect: the increase of
      ionic strength by addition of NaCl decreased PPL removal of HS.

PMID- 12201106
TI  - Use of recycling through medium size granular filters to treat small food
      processing industry effluents.
AB  - Currently there are no suitable wastewater treatment systems for effluents from
      small food processing industries (dairy, cheese, wine production). Such raw
      sewages are characterized by high organic matter concentrations (about 10 g COD L
      1) and relatively low daily volumes (about 2 m3). An adaptation of attached
      growth cultures on fine media processes, known to be easy and inexpensive to use,
      could fit both the technical and economical context of those industries. Coarser
      filter particle size distributions than those normally used allow a better
      aeration and reduce clogging risk. The transit time of the effluent through the
      porous filter materials is shortened and requires recycling to increase the
      contact time between the biomass and the substrate. A pilot plant was built to
      compare the efficiency of two kinds of filter materials, gravel (2-5 mm) and
      pozzolana (3-7 mm). Two measurement campaigns were undertaken on a full-scale
      unit dealing with cheese dairy effluents. Both pilot-scale and full-scale plants
      show high COD removal rates (> 95%). Pilot-scale experiments show that
      accumulation of organic matter leads to the clogging of the recycling filter. To
      prevent early clogging, a better definition of feeding cycles is needed.

PMID- 12201107
TI  - Important limitations in the modeling of activated sludge: biased calibration of
      the hydrolysis process.
AB  - The merit of activated sludge models depends on the accuracy and reliability of
      the information they contain on the wastewater to be treated and the biochemical
      mechanisms involved. In most advanced calibration studies, respirometry i.e. the
      measurement of the oxygen utilization rate, (OUR), provides the majority of the
      required experimental database. However, currently used procedures still involve
      a number of basic and practical problems. Model evaluation of the OUR data may
      generate a distorted image of the processes involved. Hydrolysis is the most
      important, yet the most vulnerable process as far as the experimental assessment
      of accurate kinetic parameters is concerned. This study intends to provide an
      overview of major experimental limitations in the modeling of activated sludge,
      with emphasis on the appropriate experimental design for the assessment of the
      hydrolysis rate.

PMID- 12201108
TI  - Purification of agro-industrial wastewater from the grease-protein mixture by
      means of electroflotocoagulation.
AB  - The process of agro-industrial sewage treatment with the aim of extracting grease
      from the waters is studied by means of electroflotocoagulation. A method of
      optimising the construction of electroflotocoagulation apparatus for sewage
      treatment is offered that allows passing from a laboratorial model to an
      industrial specimen that possesses the same level of technological
      characteristics. Multiple examples are given of applying electroflotocoagulation
      technology for sewage treatment from proteins and grease under different
      conditions.

PMID- 12201109
TI  - Modelling of a recirculating granular medium filter's processes.
AB  - The effluents of French small farm factories will soon be submitted to
      regulation. Only a few treatment techniques are available to deal with these kind
      of effluent (high concentration and small daily volumes). To allow the treatment,
      in the particular economic context of small food processing industries, Cemagref
      is trying to adapt a treatment based on attached growth cultures on fine media, a
      system known to be easy to operate and relatively inexpensive. A model, based on
      four sub-models (hydrodynamic characteristics, oxygen transport, solute transport
      in the mobile and immobile phases and bacterial evolution) describes this
      process. Based on wastewater concentration, hydraulic load, applied organic
      loads, feeding/rest cycles and recycling phases number, this model predicts:
      eliminated organic loads and the discharge concentration as a function of time,
      oxygen and biomass contents as a function of time and depth. The determination of
      the model's parameters is based on a comparison between simulations and
      performances achieved on experimental columns. This model would be helpful in
      sizing full-scale filters treating different types of agro-food wastewater. The
      aim of this article is to present the model's structure, to give all parameter
      values and to compare the simulations with the results obtained on pilot and full
      scale plants.

PMID- 12201110
TI  - Effect of chemical treatment on soluble residual COD in textile wastewaters.
AB  - The effect of chemical treatment on the magnitude of soluble residual COD in the
      biological treatment effluent is investigated for knit fabric finishing
      wastewater. Bentonite is selected for its potential to remove soluble COD
      together with color and particulate components. Chemical treatment using
      bentonite, when applied prior to biological treatment removes around 40% of the
      biodegradable as well as soluble inert COD initially present in the wastewater.
      As a chemical post-treatment, it acts as a polishing step, removing particulate
      matter and a minor portion of around 20% of the remaining soluble COD. These
      findings suggest chemical pre-treatment as a better alternative for the
      optimization of soluble COD removal.

PMID- 12201111
TI  - Factors affecting colour removal from reactive dye bath by ozonation.
AB  - A reactive dye bath sample containing a mixture of dyes was ozonated and colour
      removal was obtained in a relatively short time of 30 min at 605 mgl-1 of ozone
      utilisation. The factors affecting ozonation were assessed by comparing the
      results of dye bath and synthetic samples. Results from dye bath and synthetic
      dye solution ozonation were found to be significantly different. NaCl and Na2CO3
      were determined to have a slight effect only on the initial rate of ozonation.
      However, the effect of the chelating agent in terms of both time and ozone dose
      was significant and explained the differences between the results of the dye bath
      and dye solution ozonation.

PMID- 12201112
TI  - Ultimate azo dye degradation in anaerobic/aerobic sequential processes.
AB  - The treatability of Remazol Black-5 was studied in an anaerobic/aerobic
      sequential process. Laboratory scale UASB/CSTR reactors were used and operated at
      different organic loadings and HRTs to investigate the COD, color removal, and
      methane gas production efficiencies. The effect of both sludge age and HRT on the
      color and COD removal efficiencies were also investigated. The reactive dye used
      in this study contains the groups N=N, -SO3, S=O and is in use in some of the
      textile industries in Turkey. The studies were carried out in continuous mode and
      the effluent of the UASB reactor was used as feed in the CSTR reactor. COD
      removal efficiencies decreased from 56 to 27% with increases in COD loadings from
      5 kg COD/m3.day and 25 kg COD/m3.day in the anaerobic UASB reactor. The color
      removals were 92 and 87%, respectively, for the aforementioned organic loadings.
      The methane percentages were found to be 50 and 76% at organic loading rates of
      2.49 kg COD/m3.day and 14.8 kg COD/m3.day, respectively. 28, 42, and 90% COD
      removal efficiencies were obtained at sludge retention times of 1.7, 5.7 and 11
      days in the aerobic CSTR reactor. Optimum sludge age was 11 days in aerobic
      reactor and 67 and 28% COD removal efficiencies were obtained at F/M ratios of
      0.05-0.17 and 0.30-1.4 kg COD/kg MLSS.day. 90-95% color and 40-60% COD removal
      efficiencies were obtained depending on the applied organic loadings in the UASB
      reactor. The remaining COD was removed with a treatment efficiency of 85-90% in
      the aerobic CSTR reactor.

PMID- 12201113
TI  - Decolorization of textile wastewater by ozonation and Fenton's process.
AB  - The aim of this study is to investigate the effect of some operational parameters
      on the efficiency of ozonation and Fenton's process for decolorization and COD
      removal. Acid Red 337 and Reactive Orange 16 dye solutions and the effluents of
      acid and reactive dye-bath effluents were used in the experiments. The influence
      of ozone dose and pH for color and COD removal from the wastewater were studied.
      Increasing the ozone dose increased the rate constants, and color and COD removal
      efficiencies. Ozone consumption ratio per unit color and COD removal at any time
      was found to be almost the same while the applied ozone dose was different. pH
      did not significantly affect color and COD removal from the wastewater by
      ozonation. In spite of having high color removal efficiencies (60-91%), limited
      COD removal efficiencies between 9-17% at 30 minutes ozonation time were
      obtained. In the Fenton oxidation experiments, the effects of pH, temperature,
      dosage of ferrous sulfate and hydrogen peroxide, and the proper ratio of
      Fe(II)/H2O2 were studied. The result indicates that up to 99% color removal and
      82% COD removal can be obtained by Fenton's oxidation. While Fenton's oxidation
      was greatly affected by the pH value, temperature of wastewater did not
      significantly affect the Fenton process for color removal. Increasing the dose of
      both hydrogen peroxide and ferrous sulfate enhanced the removal efficiencies of
      color and COD. Suitable ratios of Fe(II)/H2O2 were found to be between 0.5 and
      0.83.

PMID- 12201114
TI  - In-plant control applications and their effect on treatability of a textile mill
      wastewater.
AB  - Water minimization and exploration of the potential for wastewater recovery and
      reuse are priority issues of industrial wastewater management. They are extremely
      significant for the textile industry commonly characterized with a high water
      demand. The study presents a detailed in-plant control survey for a wool
      finishing plant. A comprehensive process profile and wastewater characterization
      indicate that process water consumption can be reduced by 34%, and 23% of the
      wastewater volume can be recovered for reuse. Treatability of reusable wastewater
      fraction and the effect of in-plant control applications on effluent treatability
      were also investigated.

PMID- 12201115
TI  - The effect of pre-ozonation on the H2O2/UV-C treatment of raw and biologically
      pre-treated textile industry wastewater.
AB  - Advanced chemical oxidation of raw and biologically pretreated wastewater by
      ozonation, H2O2/UV-C treatment and the successive combination of ozonation and
      H2O2/UV-C oxidation was investigated. For the raw textile wastewater, the
      application of successive O3 + H2O2/UV-C oxidation enhanced the COD and TOC
      removal efficiency of the H2O2 (50 mM)/UV-C process by a factor of 13 and 4,
      respectively. In case of the biotreated textile wastewater, the preliminary
      ozonation step increased COD removal of the H2O2 (10 mM)/UV-C treatment system
      from 15% to 62%, and TOC removal from 0% to 34%, but did not appear to be more
      effective than applying a single ozonation process in terms of TOC abatement
      rates. Enhancement of the biodegradability was more pronounced for the
      biologically pre-treated wastewater with a two fold average increase in the
      BOD5/COD ratio for the studied chemical oxidation systems.

PMID- 12201116
TI  - Ozonation application in activated sludge systems for a textile mill effluent.
AB  - The study investigates the effect of partial ozonation of textile wastewater,
      both at the inlet (pre-ozonation) and the outlet (post-ozonation) of biological
      treatment, for the optimization of COD and color removals, both typical polluting
      parameters associated with the textile industry. Pre-ozonation provides at
      optimum contact time of 15 minutes 85% color removal, but only 19% COD reduction.
      Removal of the soluble inert COD fraction remains at 7%, indicating selective
      preference of ozone for simpler compounds. Post-ozonation is much more effective
      on the breakdown of refractory organic compounds and on color removal efficiency.
      Ozonation after biological treatment results in almost complete color removal and
      a 14% soluble inert COD reduction. The polishing effect of post-ozonation also
      proves quite attractive from an economical standpoint, involving approximately
      50% of the ozone utilization at the same ozone flux rate and contact time, yet
      providing a lower soluble residual COD level.

PMID- 12201117
TI  - Sustainable development of wastewater treatment strategies for the food
      industries.
AB  - The sustainable development of environmental protection is a newly created
      philosophy. It means continuous development of better protection of the air,
      soil, water and resources, used from the industry, to be saved also for future
      generations. The globalization of the economy is another process, which
      interferes with environmental ideas, and an equilibrium with the socio-eco
      sustainable development is wanted. The industry is subjected to big changes
      depending on economic development. Thus the treatment plants at the end of the
      pipe must be constructed with maximum flexibility. A removal of constructed
      devices, if not necessary, must be considered from the beginning as a
      possibility. Priority is given to integrated production processes solving
      wastewater problems directly by production devices. The treatment of the process
      wastewater streams separately will become more important. The end of the pipe
      solutions will be less complicated and more reliable. The reuse of valuable waste
      substances and treated water will reduce the total cost of the treatment plants
      substantially.

PMID- 12201118
TI  - Dairy wastewater treatment in a moving bed biofilm reactor.
AB  - Dairy raw wastewater is characterised by high concentrations and fluctuations of
      organic matter and nutrient loads related to the discontinuity in the cheese
      production cycle and machinery washing. The applicability of a Moving Bed Biofilm
      Reactor (MBBR) filled with FLOCOR-RMP plastic media to the treatment of dairy
      wastewater was evaluated in a pilot-plant. COD fractionation of influent
      wastewater, MBBR performance on COD and nutrient removal were investigated. A
      removal efficiency of total COD over 80% was obtained with an applied load up to
      52.7 gCOD m-2 d-1 (corresponding to 5 kgCOD m-3d-1). The COD removal kinetics for
      the MBBR system was assessed. The order of the kinetics resulted very close to
      half-order in the case of a biofilm partially penetrated by the substrate. The
      nitrogen removal efficiency varied widely between 13.3 and 96.2% due to the
      bacterial synthesis requirement. The application of a MBBR system to dairy
      wastewater treatment may be appropriate when upgrading overloaded activated
      sludge plants or in order to minimise reactor volumes in a pre-treatment.

PMID- 12201119
TI  - Treatment of dairy waste by using water hyacinth.
AB  - In the present study treatment of wastewater from a large dairy by using water
      hyacinth was studied in laboratory experiments. Effects of depth of the system,
      variations in area coverage, prior settling and of daily renewal of the plants
      was also studied on the efficacy of hyacinth in treating the dairy waste. Water
      hyacinth (Eichhornia crassipes) was found to grow exceptionally well in the waste
      (BOD 840.0 mg/L) and brought down the level of BOD from 840.0 to 121.0 mg/L; COD
      from 1,160.0 to 164.0 mg/L, total suspended solids from 359.0 mg/L to 245.0 mg/L,
      TDS from 848.0 mg/L to 352.0 mg/L, total nitrogen from 26.6 mg/L to 8.9 mg/L in 4
      days. There was very little reduction, however in calcium, sodium and potassium
      concentration. Results of different experiments showed that systems with shallow
      depth were more efficient in removing dissolved solids, suspended solids, BOD,
      COD, nitrogen and phosphorus. Daily renewal of the plants led to slightly better
      reduction in suspended and dissolved solids, BOD, COD and nitrogen. Water
      hyacinth coverage was found to have a direct bearing on the treatment efficiency.
      Pretreatment (settling) of the waste was also found to be favourable as dissolved
      oxygen content increased rapidly in the experimental sets with pretreatment.
      Efficiency of removal of various parameters was also good in these sets. From the
      study it can be concluded that dairy waste can be effectively treated by water
      hyacinth. Consideration of above parameters and incorporating them in design
      factors can greatly increase the efficiency of the system.

PMID- 12201120
TI  - Biological and chemical treatment of solid waste from soy sauce manufacture.
AB  - To reduce the solid waste in soy sauce refuse (SSR) that is a by-product of soy
      sauce fermentation, both biological and chemical treatment were examined. When
      anaerobic digestion of SSR was carried out at the amounts of 25 g/l under 30%
      (v/v) inocula of thermophilic methanogenic sludge at 50 degrees C, 120 mM of CH4
      was produced and 50% (w/v) of mixed-liquor suspended solids in SSR was decreased
      after 35 days. Although in this culture 30 days' cultivation was required to get
      100 mM of CH4, when the same amounts of SSR (25 g/l) were repeatedly added to the
      culture, the time requirement to get 100 mM of CH4 could be reduced to 20 days
      and 15 days at second and third batch cultures, respectively. When SSR was
      treated with 5% (w/v) NaOH for 24 h, the supernatant contained 98% (w/v) of
      protein that were alkaline-solubilized and insoluble in the intact refuse, and
      the residual pellet contained insoluble fiber.

PMID- 12201121
TI  - Biological treatability of a corn wet mill effluent.
AB  - Corn wet mill effluents are studied in terms of their characteristics relevant
      for biological treatment. They have a high COD of mainly soluble and
      biodegradable nature, with practically no soluble inert components. They generate
      a relatively high level of soluble residual metabolic products, which affects the
      choice of the appropriate biological treatment and favors aerobic activated
      sludge process. Experimental assessment of process kinetics yields typical
      values. Hydrolysis of the slowly biodegradable COD, the rate limiting step for
      the utilization of substrate, is characterized by an overall rate coefficient,
      which is within the range commonly associated for the hydrolysis of starch.

PMID- 12201122
TI  - Treatment of winery wastewater in a sequencing batch biofilm reactor.
AB  - Pilot-scale experiments were carried out applying the SBBR process (Sequencing
      Batch Biofilm Reactor) for the treatment of winery wastewater. The aim was the
      evaluation of the SBBR performance and the development of a control strategy
      based on dissolved oxygen (DO) for the optimisation of the SBBR treatment cycle
      and the minimisation of the energy supply. The results of the experimentation
      have confirmed the applicability of the SBBR process pointing out high COD
      removal efficiencies between 86% and 99%, with applied loads up to 29 gCOD m-2d
      1, corresponding to 8.8 kgCOD m-3d-1. The on-line monitoring of DO concentration
      appeared as a good indicator of the progress in the COD biodegradation. The
      control strategy for the ending of the SBBR cycles was based on the time
      derivative of the DO concentration. The optimised control strategy makes it
      possible to obtain a steady quality of the effluent wastewater with an average
      daily applied load of 6.3 kgCOD m-3d-1 rather than 3.5 kgCOD m-3d-1 for the non
      optimised SBBR cycle. The possibility of optimising the SBBR cycle through a
      simple control of the DO in the mixed liquor could be an interesting solution for
      the biological pre-treatment of winery wastewater to be discharged into sewerage
      or as a single-stage of a combined treatment plant for the discharge into surface
      water.

PMID- 12201123
TI  - Fouling of reverse osmosis and nanofiltration membranes by dairy industry
      effluents.
AB  - Fouling experiments of nanofiltration (NF) and reverse osmosis (RO) are reported
      for treatment of the effluent of chemical-biological treatment plant and the
      original effluent of dairy industry respectively. In the experiments, a thin film
      composite type of spiral wound was used and fitted with flowmeters and pressure
      sensors. The feed water was stored into a feed tank and passed a fine filter and
      was pumped to membrane. Brine and permeate were recirculated back to the feed
      tank. Membrane fouling was investigated with 16 and 30% water recovery of a
      single membrane at different pressures and flowrates for RO and NF membranes
      respectively. Fouling is evaluated with a relationship between relative flux
      (J/Jo) which is the ratio of the flux at any time during the fouling test to the
      initial flux and relative resistance (Rf/Rm) which is the ratio of fouling (cake)
      layer resistance to clean membrane resistance. Turbidity, conductivity, chemical
      oxygen demand (COD), total suspended solids (TSS) and total hardness were
      measured in the feed and permeate side of each membrane. The effluent total
      hardness concentrations of chemical-biological treatment plant were found greater
      than the influents. The results are presented in terms of the relative flux as a
      function of time related to hydrodynamic conditions and pollution characteristics
      of wastewater. The permeate water flux of RO membrane decreases more rapidly than
      NF membrane, the relative flux decreases with increasing the fouling layer
      resistance, Rf onto membrane surface. 50% the drop of permeate flux was observed
      for RO and NF membranes after 50 h and 80 h of operation, respectively. The
      fouling rate increases with an increase in the concentration of the wastewater
      constituents in the dairy industry. The relative flux decreased 10 and 20% with
      increasing chemical oxygen demand (COD) from 5,000 mgl-1 to 10,000 mgl-1 and from
      45 mgl-1 to 450 mgl-1 for RO and NF membranes, respectively after 45 h of time.
      Fouling of membranes resulted in 100% increase of specific energy consumption as
      the relative permeate fluxes of NF and RO membranes decreased 30 and 40%
      respectively. The average of specific energy consumption was obtained at 6 and 10
      kWhm-3; consequently, operational costs were estimated at U.S. $0.45 m-3 and U.S.
      $0.75 m-3 for NF and RO units respectively. Also, operational cost for chemical
      biological treatment was found at U.S. $0.30 m-3.

PMID- 12201124
TI  - Water and wastewater minimization plan in food industries.
AB  - Iran is one of the countries located in a dry and semi-dry area. Many provinces
      like Tehran are facing problems in recent years because of less precipitation.
      For reduction in wastewater treatment cost and water consumption, many research
      works have been carried out. One of them concerns food industries group, which
      consumes a great amount of water in different units. For example, in beverage
      industries, washing of glass bottles seven times requires large amounts of water
      but use of plastic bottles can reduce water consumption. Another problem is
      leakage from pipelines, valves, etc. Their repair plays an important role in the
      wastage of water. The non-polluted wasted water can be used in washing halls,
      watering green yards, recycling to the process or reusing in cooling towers. In
      this paper, after a short review of waste minimization plans in food industries,
      problems concerning water consuming and wastewater producing units in three
      Iranian food industries have been investigated. At the end, some suggestions have
      been given for implementing the water and wastewater minimization plan in the
      companies.

PMID- 12201125
TI  - Runoff characteristics of nutrients from citrus fruit grove and its effects on
      water area.
AB  - In this study, field observations are carried out in order to make clear the
      runoff characteristics of pollutants from citrus fruit grove, especially
      nutrients such as nitrogen, phosphorus and other inorganic materials. Long-term
      observation in the test fields continued for more than 7 months and detailed
      observations during one rainfall are also carried out. From these observations,
      the following results are obtained. 1) Nitrogen concentration in grove soil
      leachate is usually in a range of 25 to 45 mgN/L, and the main component is
      nitrate, whereas phosphorus concentration is in a range of 0.1 to 0.8 mgP/L and
      the main component is phosphate. Concentration of nutrients is higher than that
      in environment around it. 2) Runoff loading rate of any materials from grove soil
      can be unified and expressed as a power function of the flow rate. In this case,
      runoff style of each material is characterized by the power coefficient beta x.
      3) It is understood that the runoff characteristics are affected by the pH and
      rate of rainfall, and the ways of affecting the runoff characteristics are
      different in each material. 4) It is also suggested that detailed investigations
      are required to estimate the effect of pollutant runoff because the runoff
      characteristics are widely changed by the rainfall characteristics.

PMID- 12201126
TI  - Faecal contamination over flood events in a pastoral agricultural stream in New
      Zealand.
AB  - Faecal bacterial dynamics during flood events were studied in the Topehaehae
      Stream near Morrinsville, New Zealand, in a catchment used for grazing dairy and
      beef cattle. During the rising limb of a natural flood event, E. coli bacterial
      concentration rose by more than 2 orders of magnitude and peaked at 41,000
      cfu/100 mL. E. coli correlated closely with turbidity over the flood event, and
      both variables peaked close to the time of maximum flow acceleration rather than
      peak flow. An artificial flood on the same stream, created by releasing water
      from a supply reservoir during fine weather with no wash-in from the catchment,
      produced a broadly similar pattern of faecal contamination (peak E. coli = 12,500
      cfu/100 mL). This and other evidence suggests that direct deposition of faecal
      matter by cattle in the stream channel may be of similar or greater importance
      than wash-in from land. The flood experiments have been useful for constructing a
      model of faecal bacterial yields, and they imply that exclusion of livestock from
      stream channels may appreciably improve water quality.

PMID- 12201128
TI  - Waste management systems of dairy cattle farms in Japan.
AB  - Recently, the size of livestock farms in Japan has been expanding and the
      pollution from farm wastes has become a serious problem in rural areas. Therefore
      it is necessary to design treatment strategies and improve the recycling of
      livestock manure for sustainability of agriculture in Japan. The dairy cattle
      waste management systems were studied at dairy farms in Aomori prefecture and in
      Hokkaido, Japan. The four farms, typical for the respective regions in Japan,
      were investigated on the basis of the land and livestock size, housing, overall
      farm and waste management, type of machinery and a farm labour force. A
      statistical comparison was made for housing, milking and waste handling systems
      of dairy farms. One of the waste handling strategies was aerobic slurry treatment
      and land irrigation of the treated liquid fraction. Such methods began to solve
      some of waste management problems created since 1967 in grassland farming areas
      of Hokkaido. The irrigation system supplies water fertiliser and organic material
      to land as well as shortening the spreading times. It recycles livestock
      resources, increases the soil fertility and rationalizes the farm management.

PMID- 12201127
TI  - Sequential variation of groundwater quality in an agricultural area with
      greenhouses near the coast.
AB  - The quality of coastal groundwater utilized for greenhouse-farming is liable to
      be affected by not only fertilization practices but also seawater intrusion into
      the aquifer. In this study, the sequential variations of groundwater quality and
      the mechanisms of its pollution processes were analyzed through successive field
      measurements from June 2000 to May 2001 in such a coastal agricultural area
      located in Kochi prefecture, Japan. The analysis revealed that the ions for NO3-,
      SO4(2-), Mg2+ and Ca2+ in the groundwater originated primarily from the ground
      surface due to the seasonal flooding activities. It was also estimated that
      denitrification occurred at three well points, and the rate constants were 0.010,
      0.019 and 0.089 d-1, respectively. Na+, Mg2+ and Ca2+ concentrations in the
      groundwater governed by seawater intrusion phenomena showed strong correlations
      with the concentration of Cl- by excluding the influence of fertilizer. Cation
      exchange phenomena between Ca2+ and Na+ and as well as the mixing with seawater
      had a considerable effect on the groundwater quality.

PMID- 12201129
TI  - Development of a biological process for livestock wastewater treatment using a
      technique for predominant outgrowth of Bacillus species.
AB  - The investigation has been carried out by treating 1 m3/day of livestock
      wastewater for 9 months. The biological process is composed of two reactors
      connected in series. Each reactor has been designed to stimulate the growth of
      Bacillus sp., spore-forming aerobic or facultatively anaerobic bacteria. As a
      consequence, the population of Bacillus sp. is aptly increased via the cycle of
      sporulation, germination and proliferation. With a predominant growth of Bacillus
      sp., the microbial activity has been increased comparing to activated sludge
      based on the result of measuring specific oxygen uptake rate (SOUR). This process
      was able to remove nitrogen and phosphorus as well as organic matter efficiently.
      More than 98% of biochemical oxygen demand (BOD) and chemical oxygen demand (COD)
      were removed. In term of removing the total nitrogen (T-N), about 98% of this was
      reduced. On average, the T-N concentration in the feed was 3,270 mg/l but 74 mg/l
      in the effluent including 30 mg/l of nitrite and nitrate nitrogen. The total
      phosphorus (T-P) reduction averaged 87.5%. As a result, it would be advantageous
      to load this process in order to deal with high-strength wastewater.

PMID- 12201130
TI  - Combined biological and physico-chemical treatment of filtered pig manure
      wastewater: pilot investigations.
AB  - Combined biological and physico-chemical treatment of filtered pig manure
      wastewater has been investigated on the pilot installation operated under ambient
      temperatures (15-20 degrees C) and included: i) UASB-reactor for elimination of
      major part of COD from the filtrate; (ii) stripper of CO2 + fluidised bed
      crystallisator for phosphate (and partially ammonia) removal from the anaerobic
      effluents in the form of insoluble minerals-struvite (MgNH4PO4) and
      hydroxyapatite (Ca5(PO4)3OH); (iii) aerobic-anoxic biofilter for polishing the
      final effluent (elimination of remaining BOD and nutrients). Under overall
      hydraulic retention time (HRT) for the system of 7.8 days, the total COD,
      inorganic nitrogen and total phosphorous removals were 88, 65 and 74%,
      respectively. A decrease of the overall HRT to 4.25 days led to 91, 37 and 82%
      removals for total COD, inorganic nitrogen and total phosphorus removals,
      respectively. The approaches for further improvement of effluent quality are
      discussed.

PMID- 12201131
TI  - Optimization of nitrogen removal from piggery waste by nitrite nitrification.
AB  - The piggery waste characteristics greatly vary with types of manure collections
      and the amount of water used. If solids are separated well, the waste strength
      will be greatly reduced resulting in lower TCOD/TKN ratio of 4 (average). If
      solids are separated by a mechanical scraper, some solids will remain and the
      waste strength will be increased with a TCOD/TKN ratio of 7. This study was
      conducted to find an optimum operating condition for nitrogen removal with these
      two ratios. Nitrite nitrification was targeted because it could be a short cut
      process for savings in oxygen for nitrification and carbon requirements for
      denitrification. The study results indicated that nitrogen loading rate and pH
      were the most important factors to be considered for stable nitrite
      nitrification. The applicable nitrogen loads were estimated to be 0.3 to 2.0
      kgTKN/oxic m3/d for high TCOD/TKN ratio without pH control. With higher pH > 8,
      NO2N/NOxN ratios in oxic stages even with lower nitrogen loads were increased.
      The SBR with low TCOD/TKN ratio less than 4 required additional alkalinity. For a
      complete denitrification, the influent TCOD/TKN ratio must exceed 6 with
      oxic/total reactor volume ratio of 0.5. Nitrite nitrification and denitrification
      could save about 35% in tank volume and 50% in carbon requirement, respectively.
      However, 9.5% oxygen saving could be expected during the operation with low
      TCOD/TKN ratio. The elevated temperature due to the heat released from COD
      removal also enhanced microbial activities for nitrification and denitrification
      as well as ammonia stripping. However, careful attention must be provided for the
      reactor temperature not to inhibit the nitrification process.

PMID- 12201132
TI  - The production of D-xylose by enzymatic hydrolysis of agricultural wastes.
AB  - Agricultural wastes, rich in D-xylose content, were hydrolyzed using the mixed
      crude enzymes produced by Penicillium sp. AHT-1 and Rhizomucor pusillus HHT-1.
      Shells of pistachio, peanut, walnut, chestnut, barley brans and sunflower seed
      peels, were used as raw or pretreated forms. Pretreatment was performed by
      milling or steam explosion. Enzymatic hydrolysis after steam explosion was more
      effective than milling processing. More than 13 g of D-xylose was produced from
      100 g of milled pistachio shells, walnut shells, sunflower seed peels and peanut
      shells (less than 0.5 mm size) by the action of mixed enzyme solutions. A maximum
      of 36 g of D-xylose was produced from 100 g of milled pistachio shells when mixed
      enzyme solution, containing 3,000 U and 33 U per g of substrate with xylanase and
      beta-xyosidase activities, respectively, was applied. The ratio of the enzymatic
      hydrolysis as compared to acid hydrolysis in this finding was 100%.

PMID- 12201133
TI  - Feasibility study for production of 175Yb: a promising therapeutic radionuclide.
AB  - Owing to its favourable decay characteristics 175Yb (T1/2 = 4.2 d, E beta(max) =
      480 keV) can be regarded as a potential radionuclide for therapeutic
      applications. Production of 175Yb using (174Yb(n, gamma)175Yb) reaction by
      thermal neutron bombardment on natural ytterbium target is described. The
      activity of 175Yb produced as well as its radionuclidic purity under different
      irradiation conditions were determined by gamma-ray spectrometry using an HPGe 4
      K MCA system and compared with theoretically calculated values. The radiochemical
      purity after chemical processing was determined by paper chromatography as well
      as paper electrophoresis techniques. It is found that 31 Ci/g (1145 GBq/g) of
      175Yb can be produced with > 95% radionuclidic purity (with approximately 3% of
      169Yb and approximately 2% of 177Lu) by irradiating natural Yb2O3 target at a
      thermal neutron flux of 3 x 10(13) n/cm2/s for a period of 5 d.

PMID- 12201134
TI  - High-yield, low-pressure [18O] water targets of titanium and niobium for F-18
      production on MC-17 cyclotrons.
AB  - Large volume low-pressure targets were designed for use on the wide-beam
      Scanditronix MC-17 cyclotron. The design was optimized experimentally by
      construction of aluminum test targets. Final production targets were constructed
      of titanium and niobium. The targets tripled the routine production yield of the
      previous target, giving up to 90 GBq (2.5 Ci) of fluoride and essentially
      eliminated the need for periodic target maintenance. The final targets represent
      a considerable improvement. However, they have not performed as well as
      predicted, indicating that further improvement is possible.

PMID- 12201135
TI  - Preparation of 103Pd seed-molecular plating of 103Pd onto silver rod.
AB  - A method for 103Pd "molecular plating" onto the surface of a silver rod is
      reported. The optimal composition of the plating bath is as follows: palladium
      chloride 0.1 mol/l, formaldehyde 2 mol/l, nitric acid 1 mol/l, and formic acid
      0.4 mol/l. The 103Pd molecular plating procedure will last 25 min at 30 degrees
      C. This article provides a valuable experience for the preparation of 103Pd
      brachytherapy seed.

PMID- 12201136
TI  - Evaluation of 90Y-DTPA and 90Y-DOTA for potential application in intra-vascular
      radionuclide therapy.
AB  - 90Y-1,4,7,10-tetraazacyclododecane tetraacetic acid (90Y-DOTA) and 90Y-diethylene
      triamine pentaacetic acid (90Y-DTPA) complexes were studied for possible use in
      intra-vascular radionuclide therapy (IVRNT). 90Y was obtained from a 90Sr-90Y
      generator based on supported liquid membrane technique. The 90Y-DOTA and 90Y-DTPA
      complexes were prepared under optimised conditions. Bio-distribution of the
      complexes in Swiss mice showed that nearly 90% of 90Y complexes of both the
      ligands were excreted via urine within 1 h post-injection with negligible
      localisation in vital organs. Probenecid inhibition studies showed that both
      complexes are excreted by glomerular filtration. The predominant and quick
      excretion of 90Y-DOTA and 90Y-DTPA through the kidneys suggest that both these
      complexes could be explored for use in IVRNT.

PMID- 12201137
TI  - Radiotracer investigations in aniline production reactors.
AB  - Radiotracer investigations were carried out to measure the residence time
      distribution (RTD) of the heat transfer medium (HTM) in two identical aniline
      production reactors. One was operating abnormally while the other functioned
      normally. Investigations were carried out to identify the cause(s) of inadequate
      heat transfer from the tube-side to the shell-side of the abnormally operating
      reactor. For measuring the RTD of the HTM in the shell-side of the reactor. 82Br
      as paradibromobenzene was used as a tracer. The analysis of the measured RTD data
      revealed that about 60% of the shell-side volume of the abnormally operating
      reactor was fouled/dead, this being the root cause of the inadequate heat
      transfer. The modelling of RTD data indicated undesired parallel flow streams in
      the shell-side of the abnormal reactor. Shutdown of the abnormally operating
      reactor was instituted to allow remediation, fouling subsequently being visibly
      confirmed. The planned shutdown resulted in reduction in downtime, with
      substantial economic benefit to the industry.

PMID- 12201138
TI  - A Monte Carlo evaluation of the dosimetric characteristics of the Best Model 2301
      125I brachytherapy source.
AB  - Recently a new design of a 125I brachytherapy source was introduced for
      interstitial seed implants, particularly for prostate seed implants. This new
      source is the Best Model 2301 brachytherapy source. Due to the differences in
      source design and manufacturing process from one new source to the next, their
      dosimetric parameters should be determined according to the AAPM TG-43
      guidelines. As per AAPM recommendation (Med. Phys. 25 (12) (1998) 2269), it is
      required to perform the seed dosimetry using at least one experimental study and
      one Monte Carlo simulation, preferably done by two separate investigators. Other
      investigators have experimentally determined the dosimetric parameters of this
      new source. In this project, the Monte Carlo simulated dosimetric parameters of
      the Best Model 2301 125I source have been provided. The results of this
      evaluation indicate the value of dose rate constant of 1.01 +/- 3% cGyh-1U-1 in
      liquid water, which is in good agreement with 1.02 +/- 8% cGyh-1U-1 reported by
      Nath and Yue, 2002. The anisotropy constant was found to be 0.98 in liquid water.

PMID- 12201139
TI  - Development of an automated system for synthesizing 18F-labeled compounds using
      [18F]fluoroethyl bromide as a synthetic precursor.
AB  - An automated system was developed to synthesize 18F-labeled compounds using
      [18F]fluoroethyl bromide ([18F]FEtBr) as a synthetic precursor. The apparatus
      makes possible the following sequence of processes: (1) production of an aqueous
      solution of [18F]fluoride ([18F]F-), (2) recovery of [18F]F- from target chamber,
      (3) drying of [18F]F-, (4) formation and distillation of [18F]FEtBr into a
      trapping vessel, (5) alkylation of target compounds with [18F]FEtBr, (6) High
      performance liquid chromatography purification and (7) formulation. [18F]FEtBr,
      the synthetic precursor for fluoroethylation, was labeled via nucleophilic
      displacement of 2-trifluoromethanesulfonyloxy ethylbromide (BrCH2CH2OTf) with
      [18F]F- and was purified from the reaction mixture by distillation. After the
      conditions for forming [18F]FEtBr and drying [18F]F- were optimized, [18F]FEtBr
      was obtained in a radiochemical yield of 71 +/- 13% (n = 21, based on [18F]F-,
      corrected for decay) and a radiochemical purity of 98 +/- 1.4% at end of the
      syntheses (EOS). Using this automated system, [18F]fluoroethylspiperone
      ([18F]FEtSP) was prepared by reacting spiperone with [18F]FEtBr in a
      radiochemical yield and purity of 56 +/- 12% (n = 5, based on [18F]FEtBr,
      corrected for decay) and 97 +/- 1.5% with a specific activity of 310 +/- 120
      GBq/mumol at EOS. The total synthesis time was 55 +/- 2.3 min from the end of
      bombardment and the developed system has proved to be reliable and reproducible.

PMID- 12201140
TI  - Tritium labelling and characterization of the antimalarial drug (+/-)-chloroquine
      by several methods.
AB  - To study its mechanism of antimalarial action, a tritium labelled analogue of (+/
      )-chloroquine was required at high specific activity. Two synthetic methods were
      successfully employed. [3-3H] (+/-)-Chloroquine 2 was prepared by the catalytic
      tritium dehalogenation of an iodo precursor and [N-ethyl-3H] (+/-)-chloroquine 4
      was synthesized by the alkylation of (+/-)-desethylchloroquine with [3H] ethyl
      iodide.

PMID- 12201141
TI  - [18F]fluoromethyl triflate, a novel and reactive [18F]fluoromethylating agent:
      preparation and application to the on-column preparation of [18F]fluorocholine.
AB  - The production and use of [18F]fluoromethyl triflate ([18F]CH2FOTf), a more
      reactive [18F]fluoromethylating agent than [18F]fluoromethyl bromide
      ([18F]CH2BrF), is described. [18F]CH2FOTf was prepared from [18F]CH2BrF. The
      latter was synthesized by nucleophilic substitution of CH2Br2 with no-carrier
      added [18F]fluoride and purified by four Sep-Pak Plus silica cartridges connected
      in series. It was then quantitatively converted on-line to [18F]CH2FOTf by
      passing through a heated AgOTf column. Decay-corrected radiochemical yields of
      [18F]CH2FOTf based on [18F]fluoride were 47 +/- 8% (n = 20). Both [18F]CH2BrF and
      [18F]CH2FOTf were applied to solid-supported [18F]fluoromethylation of N,N
      dimethylaminoethanol on a Sep-Pak Plus C18 cartridge to produce the 18F-labeled
      choline analogue, (beta-hydroxyethyl)dimethyl-[18F]fluoromethylammonium
      ([18F]fluorocholine). Depending on flow rate and amount of precursor used, decay
      corrected radiochemical yields of [18F]fluorocholine from [18F]CH2BrF ranged from
      6% to 63%, while [18F]CH2FOTf afforded yields of more than 80%. Thus, by using
      the latter reagent and a subsequent purification on a Sep-Pak Accell CM
      cartridge, [18F]fluorocholine was produced from [18F]fluoride in overall
      radiochemical yields of 40% (decay corrected) in less than 30 min.

PMID- 12201142
TI  - An evaluation of measurement uncertainties in the on-line measurement of coal ash
      content by gamma-ray transmission.
AB  - In this paper, a significant effect producing systematic errors in the on-line
      measurement using gamma-ray transmission is revealed. Ash content fluctuations or
      thickness changes lead to a permanent negative systematic error in the results of
      the measurements. To study uncertainties in the measurements applicable to time
      independent ash content indicators and to investigate the characteristics of the
      radiation attenuation process, the behavior of the quantity in question in
      modeled with a stationary Gaussian distribution. A systematic error-producing
      effect has been found, and a quantitative correction is given to compensate for
      it. For some other quantities in question that vary in time, a linear model is
      used to discuss the systematic errors in the case of automated coal gangue
      separator. Results of experiments that demonstrate different systematic errors
      for different sampling intervals are presented. The reason for these errors is
      the nonlinearity of the relationship between the radiation intensity, on the one
      hand, and the sample thickness and mass attention, on the other.

PMID- 12201144
TI  - On the use of surface neutron-gamma gauges to estimate soil water content.
AB  - Surface neutron-gamma gauges are handy instruments to measure soil water contents
      and bulk densities of surface layers. Although available for some decades, their
      optimal use is still not well established. This study is a contribution to
      improve their use, mainly in relation to calibration, and of the effect of soil
      dry bulk density on soil water content measurements.

PMID- 12201143
TI  - A novel approach for the adsorption of iodine-125 on silver wire as matrix for
      brachytherapy source for the treatment of eye and prostate cancer.
AB  - The adsorption of iodine-125 on silver wire bits coated with palladium to be
      sealed in titanium capsules as brachytherapy sources was studied. A method was
      optimized to obtain quantitative adsorption of 125I on the palladium treated
      silver wires. A comparative evaluation of palladium coated and uncoated (bare)
      silver wires on the adsorption of 125I was made. While, the adsorption of bare
      silver wires showed low, inconsistent uptake (approximately 60%) of 125I with
      high leachability (approximately 4%), the Pd coated silver wires showed
      quantitative and consistent uptake of 125I (approximately 90%) and exhibited low
      leachability (0.01%). 125I adsorbed on Pd coated silver wires could be used as a
      matrix for the preparation of interstitial sources in eye and prostate cancer
      therapy.

PMID- 12201145
TI  - Gamma-ray computed tomography to characterize soil surface sealing.
AB  - The application of sewage sludge as a fertilizer on soils may cause compacted
      surface layers (surface sealing), which can promote changes on soil physical
      properties. The objective of this work was to study the use of gamma-ray computed
      tomography, as a diagnostic tool for the evaluation of this sealing process
      through the measurement of soil bulk density distribution of the soil surface
      layer of samples subjected to sewage sludge application. Tomographic images were
      taken with a first generation tomograph with a resolution of 1 mm. The image
      analysis opened the possibility to obtain soil bulk density profiles and average
      soil bulk densities of the surface layer and to detect the presence of soil
      surface sealing. The sealing crust thickness was estimated to be in the range of
      2-4 mm.

PMID- 12201146
TI  - Comprehensive Monte Carlo calculations of AAPM Task Group Report No. 43 dosimetry
      parameters for the Model 3500 I-Plant 125I brachytherapy source.
AB  - The Model 3500 I-Plant 125I brachytherapy source, produced by Implant Sciences
      Corporation, is created through a novel technique which utilizes ion implantation
      of 124Xe into a ceramic matrix followed by neutron activation of the substrate.
      Clinical dosimetry parameters were calculated using MCNP. For data processing, a
      0.376 cm active length was used for the geometry function. The 2-D anisotropy
      function, F(r, 0), exhibited less anisotropy than the Amersham Health Model 6711
      source, and decreased as radial distance, r, increased. The anisotropy constant,
      phi an, was 0.933; dose rate constant, lambda, was 1.017 +/- 0.005 cGy/h/U; and
      radial dose function, g(r), for r = (0.1, 0.2, 0.5, 2, 5, 10 cm) was 0.990,
      1.014, 1.030, 0.872, 0.448, and 0.114, respectively. In general, there was good
      agreement with experimental results recently obtained by others using
      thermoluminescent dosimeters.

PMID- 12201147
TI  - Validation of a neutron activation analysis method using k0-standardization.
AB  - A neutron activation analysis method using k0-standardization has been adopted
      for multielement analysis using our research reactors. Gold has been used as the
      comparator. The input parameters, used for calculation of elemental
      concentration, such as subcadmium to epithermal neutron flux ratio (f), the
      epithermal neutron flux shape factor (alpha), and the absolute efficiency of the
      detector (epsilon) have been determined. The values of k0-factors and Q0 (the
      ratio of resonance integral to thermal neutron cross section) have been taken
      from the literature. The validity of applying this method in our laboratory is
      evaluated by analyzing the elemental concentrations with respect to the certified
      values in eight reference materials of different origin obtained from USGS, IAEA
      and NIST. The percent deviation of the measured elemental concentrations are
      found to be within +/- 15% to that of the certified values whereas the percent
      relative standard deviation ranged from 2% to 10% for most of the elements
      analyzed.

PMID- 12201148
TI  - A decay study of 70As.
AB  - The excited states of the 70Ge nucleus in radioactive decay of 70As were
      investigated. Four new transitions with 1036.99, 1196.66, 1539.29 and 2531.7 keV
      have been found. The placement of 2219.34 keV transition has been reassigned,
      three gamma-rays with 496.74, 1295.24 and 1417.24 keV have been placed in the
      decay scheme for the first time, and the placements of 1881.67, 2325.42 and
      2424.41 keV gamma-rays are confirmed in the present work. Two new levels at
      4243.10 and 5265.81 keV excitation energy, respectively, are proposed. The level
      scheme was established and for a number of levels spin-parity assignments are
      suggested on the basis of log ft values and gamma-branching ratios.

PMID- 12201149
TI  - Dosimetric properties of various colored commercial glasses.
AB  - Brazilian commercial glasses of various colors (bronze, brown and green) have
      been studied to evaluate their potential as radiation-sensitive materials in
      gamma high-dose dosimetry. Characteristics of their optical absorption responses
      (reproducibility, room temperature stability, and calibration curves) have been
      obtained using a spectrophotometer and a simple densitometer specially designed
      for glass samples. The glass spectra feature a decay at room temperature that has
      to be taken into consideration. The results show that the colored glasses can be
      used in dosimetry; the upper limit of the dose range depends on the glass type.

PMID- 12201150
TI  - Propagation of the uncertainties of sample position to the uncertainty of the
      counting efficiency in gamma-ray spectrometry.
AB  - The uncertainties generated by inaccurate positioning of homogeneous cylindrical
      samples are propagated into the uncertainty of the counting efficiency. In this
      work general expressions describing the uncertainty of the counting efficiency in
      terms of the sample and detector properties are derived. The uncertainty of the
      counting efficiency generated by the uncertainty of the sample-detector distance
      is evaluated using the point detector concept. The uncertainty generated by the
      displacement of the symmetry axes of the sample and the detector is evaluated
      using the empirical radial dependence of the efficiency for point sources.
      Results are presented for some counting geometries resembling counting conditions
      frequently used in actual measurements. The results of the evaluations are
      compared to experimentally measured results and are briefly discussed.

PMID- 12201151
TI  - Environmental pollutant isotope measurements and natural radioactivity assessment
      for north Tushki area, south western desert, Egypt.
AB  - Natural radioactive materials under certain conditions can reach hazardous
      radiological levels. The natural radionuclide (238U, 232Th, 40K) contents of rock
      samples at various locations in the North Tushki area were investigated using
      gamma-spectrometric analysis. Estimates of the measured radionuclide content have
      been made for the absorbed dose rate of gamma radiation. The equivalent radium
      (Req) and the external hazard index (Hex) which resulted from the natural
      radionuclides in soil are also calculated and tabulated. The studied samples have
      been collected from various rock exposures in the North Tushki area. The
      distribution of major oxides, U and Th were studied. It is found that the
      enrichment and depletion of the major oxides are mainly due to the effect of
      hydrothermal alteration, which caused mobility of some major oxides, which
      increases some elements and decreases others. It is important to mention that the
      study area is far from the development region of the Tushki project and is only a
      local hazard. Therefore, additional regional studies of the Tushki Project area
      should be under taken to explore any unexpected environmental hazard due to the
      high concentration of the radioactive elements, which have been observed at its
      north boundary.

PMID- 12201152
TI  - Development of a gamma-gamma-perturbed angular correlation one-detector method (1
      PAC) for investigation of physico-chemical properties of matter.
AB  - A new method of the perturbed angular gamma-gamma-correlation (PAC) measurements
      was developed using one HPGe detector only (1-PAC). For quantifying the
      perturbation factor, the ratio R gamma 1 + gamma 2 of the summing peak composed
      of two cascade gamma-rays (the perturbation-affected parameter) to the summing
      peak composed of one gamma-ray and one X-ray (the perturbation non-affected
      parameter) was used. This method was demonstrated for the radionuclides 111In and
      111mCd, identifying the chemical status of the radionuclides in aqueous
      solutions.

PMID- 12201153
TI  - Study of variance and covariance terms in linear attenuation coefficient
      measurements of irregular samples through the two media method by gamma-ray
      transmission.
AB  - The two media method permits the application of Beer's law (Thesis (Master
      Degree), Universidade Estadual de Londrina, PR, Brazil, pp. 23) for the linear
      attenuation coefficient determination of irregular thickness samples by gamma-ray
      transmission. However, the use of this methodology introduces experimental
      complexity due to the great number of variables to be measured. As consequence of
      this complexity, the uncertainties associated with each of these variables may be
      correlated. In this paper, we examine the covariance terms in the uncertainty
      propagation, and quantify the correlation among the uncertainties of each of the
      variables in question.

PMID- 12201154
TI  - MCNP modelling of scintillation-detector gamma-ray spectra from natural
      radionuclides.
AB  - gamma-ray spectra of natural radionuclides are simulated for a BGO detector in a
      borehole geometry using the Monte Carlo code MCNP. All gamma-ray emissions of the
      decay of 40K and the series of 232Th and 238U are used to describe the source. A
      procedure is proposed which excludes the time-consuming electron tracking in less
      relevant areas of the geometry. The simulated gamma-ray spectra are benchmarked
      against laboratory data.

PMID- 12201155
TI  - Keep the lifeboat afloat.

PMID- 12201156
TI  - Chronic neglect of family violence: more than a decade of reports to guide US
      policy.
AB  - For more than a decade, several boards and committees have reviewed the state of
      policy, research, and services on child maltreatment and other forms of family
      violence in the US. Although these efforts have resulted in a redefinition of the
      tasks involved in protecting people within their homes, this new
      conceptualization has yet to have a substantial effect on policy, research, and
      services. Some positive steps have been taken, but most are still modest in
      scope. They may be dwarfed by the growing challenges in family and community
      life.

PMID- 12201157
TI  - Challenges facing child protection.
AB  - The challenges facing children in the 21st century are immense and will need to
      be faced if we are to achieve the goal of child protection for all. Three
      specific constraints on child protection are examined in this article, namely
      poverty, HIV/AIDS infection, and war. The authors use their experience in Africa
      to raise issues of resilience and adaptation, dangers to child protection
      programs, and possible solutions. Poverty can be both financial and
      psychological, and this affects the effect of prevention programs. In many
      African and Asian countries, the AIDS pandemic has changed the social structure
      of society with AIDS orphans and children infected and affected by HIV/AIDS
      becoming more common. The impact has devastating effects on the way we view child
      protection and in particular child sexual abuse. The consequences of post
      traumatic stress resulting from war needs to be addressed, and the development of
      programs that place children in the center of relief programs to foster a culture
      of child protection is essential. Finally, the article notes that the picture is
      not overly pessimistic and the examines the achievements in the field of
      children's rights which underpin all programs aimed at protecting children and
      the future need to consolidate successes achieved.

PMID- 12201158
TI  - Child fatality review: an international movement.
AB  - OBJECTIVE: This article discusses the multidisciplinary Child Fatality Review
      process in the US, Canada, and Australia, including common patterns, unique
      programs, changes over time, impact on multiagency systems, and future
      directions. METHOD: An open-ended survey was shared with teams listed in the
      directories of the Los Angeles County Inter-Agency Council on Child Abuse and
      Neglect National Center on Child Fatality Review (ICAN-NCFR). Responses were
      received from 58 state and local Child Fatality Review teams. RESULTS: Teams
      exist in all 50 states, Washington, DC, most Canadian provinces, and New South
      Wales, Australia. Team structure varies but generally includes a similar core
      membership, and most teams select cases from coroner/medical examiner or vital
      statistics records through established protocols. While most case review is
      conducted by local teams, state teams may review cases because of small size or
      sparse population or choose to review specific types of cases (e.g., Child
      Protective Services). State teams often support local review through training,
      resources, policy development, and political assistance. An increasing number of
      teams collect data and issue reports, often published on the internet, allowing
      teams to share resources. CONCLUSIONS: Teams have matured with time, often
      broadening their intake spectrum, membership and data collection, and developing
      and following through with case management or systems change recommendations.
      Teams continue to improve multiagency interaction and are committed to the
      prevention of child injury and death. The number of teams, as well as their scope
      and expertise, continues to increase, developing into a national/international
      system.

PMID- 12201159
TI  - Culture and child maltreatment: cultural competence and beyond.
AB  - OBJECTIVE: The objective of this article is to comment on current issues in the
      relationship between culture and child maltreatment. METHOD: A review of the
      literature on culture and child maltreatment is the basis of the article. RESULTS
      AND CONCLUSION: While attention has been directed to the relationship between
      culture and maltreatment for more than 20 years, there is a need for further
      development in this area. Efforts need to be made to "unpack" culture, to promote
      understanding culture in context, and to enhance research on child maltreatment
      and culture.

PMID- 12201160
TI  - Children referred for possible sexual abuse: medical findings in 2384 children.
AB  - OBJECTIVE: The goal of this study was to compare rates of positive medical
      findings in a 5-year prospective study of 2384 children, referred for evaluation
      of possible sexual abuse, with two decades of research. The prospective study
      summarizes demographic information, clinical history, relationship of
      perpetrators, nature of abuse, and clinical findings. The study reports on the
      results by patterns of referral and the medical examination. RESULTS: There were
      2384 children evaluated in a tertiary referral center between 1985 and 1990 for
      possible sexual abuse. Children were referred after they disclosed sexual abuse,
      because of behavioral changes or exposure to an abusive environment, and because
      of possible medical conditions. A total of 96.3% of all children referred for
      evaluation had a normal medical examination; 95.6% of children reporting abuse
      were normal, 99.8% who were referred for behavioral changes or exposure to abuse
      were also normal. Of the 182 children referred for evaluation of medical
      conditions, 92% were found to be normal at the time of examination by the Child
      Advocacy Center. The remaining 15/182 (8%) that were found to be abnormal were
      diagnosed with sexually transmitted diseases, acute or healed genital injuries,
      and were 17% (15/88) of the total cases found to have medical findings diagnostic
      of abuse. Interviews of the children indicated that 68% of the girls and 70% of
      the boys reported severe abuse, defined as penetration of vagina or anus.
      Penetration was associated with a higher percentage of abnormal findings in girls
      (6%) compared to 1% of the boys. The relationship of the abuser impacted on the
      severity of the abuse. CONCLUSION: Research indicates that medical, social, and
      legal professionals have relied too heavily on the medical examination in
      diagnosing child sexual abuse. History from the child remains the single most
      important diagnostic feature in coming to the conclusion that a child has been
      sexually abused. Only 4% of all children referred for medical evaluation of
      sexual abuse have abnormal examinations at the time of evaluation. Even with a
      history of severe abuse such as vaginal or anal penetration, the rate of abnormal
      medical findings is only 5.5%. Biological parents are less likely to engage in
      severe abuse than parental substitutes, extended family members, or strangers.

PMID- 12201161
TI  - Preventing sexually abused young people from becoming abusers, and treating the
      victimization experiences of young people who offend sexually.
AB  - OBJECTIVE: This study was designed to determine whether it is possible to prevent
      those sexually abused boys who are at risk of abusing other children from doing
      so, and to assess whether factors associated with an experience of sexual abuse
      in young people who are offending can be dealt with as a key aspect of
      therapeutic work alongside treatment of offending behavior. METHOD: The author
      examined cross-sectional and longitudinal research which demonstrates the impact
      on sexually abused children of living in a climate of violence, suffering
      physical abuse, exposure to abuse of maternal figures, and suffering disruption
      and poor quality of care and supervision. These factors are confirmed in
      prospective research. RESULTS: The application of these findings to therapeutic
      programs for boys who are sexually abused is described, including the assessment
      of care needs as well as the specific therapeutic work with the young person, and
      work to modify the family context. The specific treatment of victimization
      experiences in young people who have committed sexual offenses is also examined,
      with recommendations for modification of treatment approaches suggested.
      CONCLUSION: It is vital in therapeutic work with boy victims of sexual abuse that
      the issue of their abusive potential be considered, even if a relatively small
      proportion of such boys will go on to abuse others. Given that boys who do
      sexually abuse are likely to have grown up in a climate of violence and poor
      care, methods of dealing with such victimization experiences need to be developed
      alongside offending focused treatments.

PMID- 12201162
TI  - Child neglect: developmental issues and outcomes.
AB  - OBJECTIVE: This article highlights the manner in which child neglect, the most
      common form of maltreatment, affects children's development. METHOD: The review
      is organized according to three developmental periods (i.e., infancy/preschool,
      school-aged and younger adolescents, and older adolescents and adults) and major
      developmental processes (cognitive, social-emotional, and behavioral). Although
      the focus is on specific and unique effects of various forms of child neglect,
      particular attention is paid to studies that allow comparisons of neglect and
      abuse that clarify their similarities and differences. RESULTS: Past as well as
      very recent findings converge on the conclusion that child neglect can have
      severe, deleterious short- and long-term effects on children's cognitive, socio
      emotional, and behavioral development. Consistent with attachment and related
      theories, neglect occurring early in life is particularly detrimental to
      subsequent development. Moreover, neglect is associated with effects that are, in
      many areas, unique from physical abuse, especially throughout childhood and early
      adolescence. Relative to physically abused children, neglected children have more
      severe cognitive and academic deficits, social withdrawal and limited peer
      interactions, and internalizing (as opposed to externalizing) problems.
      CONCLUSIONS: The current review offers further support for the long-standing
      conclusion that child neglect poses a significant challenge to children's
      development and well-being. Limitations with regard to the state of the knowledge
      are discussed and directions for future research are outlined.

PMID- 12201163
TI  - Emotional abuse and neglect (psychological maltreatment): a conceptual framework.
AB  - OBJECTIVE: Emotional abuse and neglect is an under-recognized, but actually
      common, form of child abuse. Professionals in the field continue to find
      difficulty in recognizing and operationally defining it, and experience
      uncertainty about proving it legally. There are also questions about intervention
      and therapy to protect the child in the least detrimental manner. These
      difficulties have led to delays in recognition and protective intervention.
      Emotional abuse and neglect are defined as a carer-child relationship that is
      characterized by patterns of harmful interactions, requiring no physical contact
      with the child. Motivation to harm the child is not necessary for the definition.
      Unlike sexual abuse that is a secret activity, these forms of ill treatment are
      easily observable. The child's development is impaired in all domains of
      functioning but, not being specific to emotional abuse and neglect, cannot be
      regarded as diagnostic. METHOD: Research, clinical experience and theoretical
      considerations have led to a conceptual framework and operational definitions of
      five categories of harmful interactions between parent and child. This framework
      is contrasted with the APSAC categories. RESULTS: It is postulated that the
      different categories of ill treatment respectively require different therapeutic
      interventions. CONCLUSION: Concerns about the presence of emotional abuse need to
      trigger an assessment process that includes identifying the nature of the abusive
      or neglectful interactions and a time-limited trial of specific interventions.
      The family's response to this process and its outcome will determine the need for
      statutory involvement, as well as providing a basis for litigation if this is
      required.

PMID- 12201164
TI  - The health effects of childhood abuse: four pathways by which abuse can influence
      health.
AB  - OBJECTIVES: This article describes four possible pathways by which childhood
      abuse relates to health problems in adults. METHOD: Literature on the long-term
      effects of childhood abuse is organized in a health psychology framework
      describing behavioral, social, cognitive, and emotional pathways. Key studies
      from the health psychology and behavioral medicine literature are included to
      demonstrate how these pathways relate to health. RESULTS: Childhood abuse puts
      people at risk of depression and post-traumatic stress disorder, participating in
      harmful activities, having difficulties in relationships, and having negative
      beliefs and attitudes towards others. Each of these increases the likelihood of
      health problems, and they are highly related to each other. CONCLUSIONS:
      Childhood abuse is related to health via a complex matrix of behavioral,
      emotional, social, and cognitive factors. Health outcomes for adult survivors are
      unlikely to improve until each of these factors is addressed.

PMID- 12201165
TI  - Charting the waves of prevention: two steps forward, one step back.
AB  - BACKGROUND: Over the past 30 years, the political response to child maltreatment
      and its prevention in the US has experienced periods of frantic activity, often
      followed by long periods of benign neglect. In reflecting on this history, Dick
      Krugman has referred to this uneven level of attention as a series of "waves" in
      which apparent progress is often minimized by an inability to sustain political
      commitment to a given reform or course of action. To an extent, this pattern
      reflects deep differences among child welfare advocates, researchers, and
      practitioners on how best to proceed. While most everyone agrees that "it
      shouldn't hurt to be a child," how to prevent this hurt and at what cost is less
      clear. METHOD: To address this dilemma, prevention advocates, researchers, and
      practitioners have struggled with a variety of conceptual frameworks and
      programmatic reforms. This article summarizes the relative gains and limitation
      of three such efforts and outlines the lessons these efforts offer those
      formulating future prevention policies and programs. RESULTS: Specifically, the
      authors suggest that future prevention efforts will need to take care in avoiding
      some of the most common mistakes experienced by earlier efforts. CONCLUSIONS:
      These mistakes or pitfalls include oversimplifying the problem of child abuse;
      overstating preventions' potential and appropriate target populations; failing to
      establish a significant partnership with child protective services; compromising
      depth or quality in an effort to maximize breadth or coverage; and failing to
      fully engage the public.

PMID- 12201166
TI  - [Practice guideline for allergic rhinitis].

PMID- 12201167
TI  - [The evaluation of the relationship between the residual fluticasone propionate
      dry powder after inhalation and maximum peak inspiratory flow].
AB  - We often find some residual Fluticasone propionate (FP) dry powder after using a
      specialized inhalant instrument (Diskhaler) in daily clinical use. In this study,
      we evaluated the relationship between residual powder and peak inspiratory flow
      (PIF), and the therapeutic necessity of using the reductive method of the
      residual powder. METHOD: 70 patients with bronchial asthma including 18 patients
      concurrently with COPD were measured for their maximum PIF, the residual dose of
      FP dry powder and FP content of the residual powder after inhalation. We also
      investigated effective methods to reduce residual powder. RESULT: The residual
      powder volume may be dependently affected by maximum PIF. More than 50% residual
      powder after 1 inhalation occurred in asthmatic patients with a PIF of less than
      50 L/min. Discovering almost the same FP content of dry powder residues as before
      inhalation, we recognized the therapeutic significance of the decreased residual
      dry powder. Although the method of increased inhalation frequency alone was
      limited, the combined use of nail-tapping vibration of the Diskhaler and
      increased inhalation frequency may significantly decrease the residual dry
      powder. After carrying out the nail-tapping vibration method over 3 months, we
      obtained significant increases in daily Peak expiratory flow values with no
      increased pharyngeal Candidiasis. Oral abnormal dry sensation was found in one
      person as an additional side effect. CONCLUSION: We showed the quantitative
      evaluation of the relationship between PIF and residual FP dose, while making
      clear the therapeutic meaning of the reduction of residual powder. Our nail
      tapping method may be a clinically effective method to reduce risidual FP dry
      powder.

PMID- 12201168
TI  - [The study of immunological markers in patients with "intrinsic" type atopic
      dermatitis].
AB  - Atopic dermatitis (AD) is a common inflammatory skin disease characterized by
      several clinical, immunological and biochemical alterations. Comparing the
      patients with the 'extrinsic' and 'intrinsic' types of AD, we investigated the
      role of immunological mechanisms in the pathogenesis of AD. To confirm it, we
      calculated serum markers of T lymphocyte activation: soluble interleukin-2
      receptor (sIL-2R), interleukin-4 (IL-4), interleukin-10 (IL-10) and interferon
      gamma (IFN-gamma). The soluble CD14 (sCD14) and tumor necrosis factor-alpha (TNF
      alpha) in serum were measured as monocyte/macrophage activation markers. We
      examined 29 patients with the 'extrinsic' type AD (serum IgE > 10000 IU/ml: High
      AD), 23 patients with the 'intrinsic' type AD (serum IgE < 37 IU/ml: Low-AD) and
      11 healthy controls. Serum sIL-2R levels were increased in High-AD and Low-AD
      compared with the controls. They were also significantly increased in High-AD
      compared with Low-AD. Serum sCD14 levels were increased in High-AD compared with
      Low-AD and the controls. Severity index of AD were correlated with serum sIL-2R
      levels but not with sCD14 levels in sera. In conclusion, IgE may not relate with
      the pathogenesis of atopic dermatitis. Serum sIL-2R levels may be increased
      according to inflammatory skin lesions and it may be exaggerated with the
      immunological activation in the patients with the 'extrinsic' type AD.

PMID- 12201169
TI  - [Immediate adverse reactions after administration of the influenza vaccine to
      patients with positive CAP-RAST to egg white].
AB  - We investigated the safety of administration of influenza vaccine to patients
      with positive CAP-RAST to egg white. The content of OVA in the influenza vaccine
      preparations was measured by Sandwich ELISA. The concentration of OVA in the
      vaccine preparations ranged from 2 to 8 ng/ml. We administered influenza vaccine
      to 36 high risk patients who had positive CAP-RAST (> 4 score) to egg white
      and/or had experienced immediate type hypersensitivity after ingestion of egg.
      One out of them showed local swelling. All the rest of the patients received
      influenza vaccine without any serious systemic adverse reactions. We also
      investigated the incidence of immediate adverse reactions after vaccination in
      the group of 104 patients with positive CAP-RAST to egg white compared to the
      group of 98 patients with negative CAP-RAST. No significant difference was found
      in the incidence of adverse reaction between the two groups (group of positive
      CAP-RAST to egg white: 0.5%, negative group: 2.2%). These results demonstrate
      that most of the patients with positive CAP-RAST to egg white, even those with
      allergic reactions after egg ingestion, can safely receive an influenza vaccine.

PMID- 12201170
TI  - [Japanese cedar pollinosis is a risk factor for bronchial asthma in Japanese
      adult asthmatics].
AB  - It is well known that allergic rhinitis and asthma often coexist in the same
      patients. Here, we investigated the influence of Japanese cedar pollinosis on the
      exacerbation of asthma investigated by questionnaire, daily asthma diary, and
      peak expiratory flow (PEF) monitoring. Furthermore, airway responsiveness to
      histamine before pollen season was also investigated in some patients. 333 adult
      patients with asthma were enrolled into the study and 116 patients (34.8%) were
      suffering from Japanese cedar pollinosis diagnosed by the presence of nasal
      allergic symptoms during pollen season and high titer of Japanese cedar-specific
      IgE antibody. Exacerbation of asthma symptoms, including wheezing, dyspnea,
      cough, and sputum, was detected in 41 of 116 patients (35.3%) during pollen
      season. Decrease in morning PEF more than 10% compared with the baseline values
      before pollen season was observed in 13 of 41 patients (11.2% of total asthmatic
      patients who complicated with Japanese cedar pollinosis). No significant
      differences in airway responsiveness to histamine and the titer of Japanese cedar
      specific IgE antibodies before pollen season were observed between the patients
      whose asthma exacerbated and the patients whose asthma was not exacerbated. These
      results suggest that Japanese cedar pollinosis is one of risk factors for asthma
      in Japanese adult patients with asthma.

PMID- 12201171
TI  - [The prognosis of asthmatic children with status asthmatics in early childhood].
AB  - To clarify the prognosis of asthmatic children with status asthmatics in early
      childhood, we retrospectively investigated 113 patients (boys: 62, girls: 51) who
      had been treated as status asthmatics since 1995 through 2000 in National
      Sagamihara Hospital. In this study, the frequency of admission was decreased year
      by year, 62.8% (1st year), 29.2% (3rd year), and 5% (5th year). All patients were
      evaluated as severe or moderate patients during the 1st year from the episode of
      status asthmatics. Three years after the episode, 38% of patients were evaluated
      as severe or moderate patients. Five years later, only 20% of patients were
      evaluated as severe or moderate patients and 35% became free from treatment and
      asthma attack. Most of the patients were treated by DSCG inhalation and RTC
      therapy. Nine patients needed BDI therapy in addition to DSCG and RTC. With
      appropriate and careful treatment, the prognosis of the patients who had
      experienced status asthmatics in the early childhood was kept relatively well.

PMID- 12201172
TI  - [Prediction of the total Japanese cedar pollen counts based on male flower
      setting conditions of standard trees].
AB  - We made a prediction of the Japanese cedar (Cryptomeria japonica) pollen counts
      at Tsu city based on male flower-setting conditions of standard trees. The 69
      standard trees from 23 kinds of clones, planted at Mie Prefecture Science and
      Technology Promotion Center (Hakusan, Mie) in 1964, were selected. Male flower
      setting conditions for 276 faces (69 trees x 4 points of the compass) were scored
      from 0 to 3. The average of scores and total pollen counts from 1988 to 2000 was
      analyzed. As the results, the average scores from standard trees and total pollen
      counts except two mass pollen-scattered years in 1995 and 2000 had a positive
      correlation (r = 0.914) by linear function. On the mass pollen-scattered years,
      pollen counts were influenced from the previous year. Therefore, the score of the
      present year minus that of the previous year were used for analysis. The average
      scores from male flower-setting conditions and pollen counts had a strong
      positive correlation (r = 0.994) when positive scores by taking account of the
      previous year were analyzed. We conclude that prediction of pollen counts are
      possible based on the male flower-setting conditions of standard trees.

PMID- 12201173
TI  - Characterisation & drug susceptibility patterns of extrapulmonary mycobacterial
      isolates.
AB  - BACKGROUND & OBJECTIVES: There is a paucity of information on extrapulmonary
      tuberculosis as much of the attention is focussed on pulmonary tuberculosis. This
      prospective study aimed at identification and characterisation of mycobacterial
      isolates from extra pulmonary sites and the evaluation of the drug susceptibility
      patterns of Mycobacterium tuberculosis isolates from extrapulmonary sites using
      the conventional method and the E-test. METHODS: A total of 350 specimens from
      patients of extrapulmonary tuberculosis with varied presentation, were studied.
      Speciation and characterisation of isolates were done on the basis of growth and
      biochemical characteristics. Drug susceptibility testing for M. tuberculosis
      isolates was done by proportion method for isoniazid, rifampicin, ethambutol and
      pyrazinamide, whereas resistance ratio method was used for streptomycin. E-test
      (AB Biodisk, Sweden) was carried out to compare susceptibility patterns of the M.
      tuberculosis isolates for isoniazid and rifampicin with the conventional method.
      RESULTS: Thirty two of 350 (9.14%) patients clinically suspected to have
      extrapulmonary tuberculosis were culture positive for mycobacteria. On
      characterisation, 20 of the 32 isolates were identified as M. tuberculosis and 12
      as non-tubercular mycobacteria (NTM) with 5 of the 12 being Mycobacterium avium
      complex. Among M. tuberculosis isolates both initial and acquired resistance was
      highest for streptomycin followed by isoniazid, rifampicin and ethambutol. No
      strain showed resistance to pyrazinamide. Two strains were found to be multidrug
      resistant. Drug susceptibility patterns by conventional method corroborate with
      the E-test results. INTERPRETATION & CONCLUSION: This study shows that the
      characterisation and species identification of mycobacterial isolates along with
      drug susceptibility testing help in better understanding of extrapulmonary
      tuberculosis. E-test had the advantage of being rapid and simple without need for
      additional equipment.

PMID- 12201174
TI  - Some aspects of molecular epidemiology & characterisation of Salmonella
      Typhimurium isolated from man & animals.
AB  - BACKGROUND & OBJECTIVES: Salmonellae are widely distributed in nature and cause a
      wide spectrum of diseases in man and animals. Among the different serovars of
      Salmonella enterica, S. Typhimurium is most commonly associated with enteric
      infection in man and animals. The present paper reports on the phage typing,
      plasmid profile, antimicrobial resistance and genetic diversity of Indian strains
      of S. Typhimurium isolated from man and animals. METHODS: A total of 17 strains
      of S. Typhimurium were subjected to phage typing and tested for plasmid and
      antimicrobial resistance. Genetic variability of the strains was studied by
      cleaving the whole cell DNA with restriction endonuclease, XbaI and detecting the
      restriction fragments by pulse-field gel electrophoresis (PFGE). RESULTS: All the
      17 strains were typeable and belonged to 4 phage types (DT003, DT004, DT096 and
      DT193). Three plasmid profiles were observed. Multiresistance was common. Strains
      belonged to DT193 were highly resistant to most of the antimicrobial agents
      tested and harboured 3-4 plasmids. Strains belonged to DT003, DT004 and DT096
      were found to be less resistant to antibiotics and harboured only 1 plasmid. A
      genetic variability was observed among the strains irrespective of the source of
      isolation. Twelve restriction patterns observed among the 17 strains as analyzed
      by PFGE indicated a considerable genetic heterogeneity among human and animal
      isolates. INTERPRETATION & CONCLUSION: A relationship was observed between
      resistance patterns, plasmid profiles and phage typing. Restriction analysis
      obtained by PFGE was found to be more discriminating in the differentiation of
      strains than the other methods used, and thus provides a valuable alternative
      tool for molecular characterisation of S. Typhimurium isolated from man and
      animals.

PMID- 12201175
TI  - Rising quinolone resistance in Neisseria gonorrhoeae isolates from New Delhi.
AB  - BACKGROUND & OBJECTIVES: Treatment for gonorrhoea with fluoroquinolones is
      recommended. However, reduced susceptibility and treatment failure with
      fluoroquinolones has recently been reported. We undertook to study the antibiotic
      susceptibility pattern and the incidence of quinolone resistance in 36
      consecutive isolates of Neisseria gonorrhoeae from April to November 2000.
      METHOD: Antibiotic susceptibility testing was performed by the Kirby Bauer disc
      diffusion technique and minimum inhibitory concentration (MIC) of ciprofloxacin
      was determined by the agar dilution method. Penicillinase producing N.
      gonorrhoeae (PPNG) were identified by using the nitrocefin disc method. RESULTS:
      Thirty six strains of N. gonorrhoeae obtained from 44 consecutive male patients
      (81.9%) were studied. By the disc diffusion method, only 3 (8.3%) of these
      isolates were found to be sensitive to ciprofloxacin. All isolates were sensitive
      to ceftriaxone while 23 (63.9%) were sensitive to tetracycline and 12 (33.3%) to
      penicillin. Four (11.1%) of the N. gonorrhoeae isolates were PPNG. Twenty seven
      (75%) isolates were found to be resistant to ciprofloxacin by MIC determination.
      INTERPRETATION & CONCLUSION: Incidence of ciprofloxacin resistance amongst N.
      gonorrhoeae isolates is on the rise in New Delhi. Periodic monitoring of
      antimicrobial susceptibility pattern of N. gonorrhoeae to antimicrobials other
      than quinolones is essential to prevent treatment failure in patients with
      gonorrhoea.

PMID- 12201176
TI  - Prevalence of insulin resistance syndrome in a selected south Indian population-
      the Chennai urban population study-7 [CUPS-7].
AB  - BACKGROUND & OBJECTIVES: Although earlier studies had shown socio-economic
      factors to be strongly associated with the insulin resistance syndrome (IRS) and
      its components, there is still a paucity of data on Indians who have increased
      insulin resistance. In this study, we assessed the prevalence of IRS in two socio
      economic groups in an urban south Indian population. METHODS: The Chennai Urban
      Population Study (CUPS) is an epidemiological study involving two residential
      areas in Chennal in south India. Of the 1262 eligible subjects (age > or = 20 yr)
      who participated in the study, 1070 (76.5%) subjects who had a complete set of
      data were recruited for this study. Insulin resistance was calculated using the
      homeostasis assessment (HOMA) model. Insulin resistance syndrome was defined as
      the presence of insulin resistance in combination with at least 2 of the
      following conditions: hyperglycaemia, hypertension, dyslipidemia or central body
      obesity. RESULTS: The overall prevalence of IRS was 11.2 per cent (95% confidence
      interval: 9.4-13.3). The prevalence of the IRS in the middle-income group (18.7%)
      was significantly higher compared to the low income group (6.5%; P < 0.001).
      Multiple logistic regression analysis revealed age (P < 0.001), body mass index
      (P < 0.05) and socio-economic status (P = 0.014) to be associated with IRS.
      INTERPRETATION & CONCLUSION: The overall prevalence rate of IRS was 11.2 per
      cent. Age and higher socio-economic status were the risk factors for insulin
      resistance in this selected urban south Indian study population.

PMID- 12201177
TI  - Incidence estimates of substance use disorders in a cohort from Delhi, India.
AB  - BACKGROUND & OBJECTIVES: There are no reports of incidence studies in the Indian
      setting on substance use disorders in the general population. This survey
      resurvey carried out in metropolis Delhi estimated the incidence rates of
      substance use disorders. METHODS: A cross-sectional survey was carried out at two
      points of time with an interval of one year in a representative sample from the
      general population of metropolis, Delhi. The instrument was precoded, structured
      and based on DSM III-R operationalised criteria for use of tobacco, alcohol,
      cannabis and opioids (past one month). Matched data for two points of time were
      available for 5414 males and 4898 females. RESULTS: In the total cohort, the
      annual incidence rates (per 100 persons) among males for any drug use, alcohol,
      tobacco, cannabis and opioids were 5.9, 4.2, 4.9, 0.02 and 0.04 respectively.
      Among females, incidence of any drug use was 1.2/100 persons. INTERPRETATION &
      CONCLUSION: Results showed that males have higher incidence for both not
      dependent and dependent use for all the drug categories. Females had a higher
      incidence of dependent tobacco use.

PMID- 12201178
TI  - Molecular & evolutionary genetics & drug resistance of the gastric pathogen,
      Helicobacter pylori.
AB  - Helicobacter pylori colonizes the gastric mucosa of more than half of all people
      worldwide and is the major cause of peptic ulcer disease and an early risk factor
      for gastric cancer, even though most infections are asymptomatic. Infection
      occurs preferentially in early childhood and once established tends to persist
      for years or decades. Much of the pathology H. pylori causes probably results
      from the host response to infection, which is affected by bacterial genotype,
      human host characteristics and environmental conditions. H. pylori is one of the
      most genetically diverse of bacterial species, with different genotypes
      predominating in different parts of the world. In particular, strains from India
      differ from those of Europe and East Asia in DNA sequence of several diagnostic
      gene segments. This outcome invites speculation about H. pylori origins and the
      possibility of Indian-specific genes that might be uncommon in Western strains.
      Much has been learned from H. pylori genome sequences, along with
      epidemiological, mutational, molecular and immunologic analyses. Candidate
      bacterial colonization and virulence genes and host responses are being
      identified, and the hypotheses being developed are amenable to tests in cell
      culture and animal models. These research efforts, many of which are
      collaborative and international, provide insights into mechanisms of
      establishment and persistence of H. pylori infection and virulence, and should
      lead to new, far more potent and cost effective anti-Helicobacter therapies or
      vaccines, and thereby major improvement in human health worldwide.

PMID- 12201179
TI  - Pathways to violent and non-violent criminality in an adolescent psychiatric
      population.
AB  - In a Norwegian follow-up study of former adolescent psychiatric in-patients 222
      patients who had committed violent crimes were compared to 287 patients who had
      committed non-violent crimes only. There were numerous significant differences
      between the criminal careers of violent and non-violent criminals. Individuals
      with a history of violent criminality only were uncommon and uncharacteristic of
      violent criminals in general. Regression analyses identified several strong and
      independent correlates of violent criminality. The study supported a division of
      antisocial behavior into violent and non-violent sub-groups, thus paralleling a
      concept of overt and covert pathways to delinquent behavior. The overt pathway
      seemed to be imbedded in the covert pathway.

PMID- 12201180
TI  - Precursors of mental health problems for low birth weight children: the salience
      of family environment during the first year of life.
AB  - The purpose of this study was to determine the contributions of infant
      characteristics and early family environment to the incidence of emotional and
      behavioral problems for low birth weight children. Data were collected from
      ethnically diverse families of 110 children who had a birth weight of less than
      2500 grams. Results of stepwise regression analysis indicated that inadequate
      family income, troubles with family cohesion and adaptability, and an infant's
      insecure attachment to the mother accounted for 48% of the variance in the
      incidence of emotional-behavioral problems for children. None of the infants'
      characteristics, including birth weight, perinatal morbidity, cognitive ability
      and social competence, entered the regression model. Findings suggest that family
      environment is a key factor in the low birth weight child's risk for early mental
      health problems.

PMID- 12201181
TI  - Magical beliefs and rituals in young children.
AB  - Thirty-one children were administered a structured interview that assessed their
      beliefs about magic, tricks and wishes. Children were also presented with
      demonstrations of magic tricks/illusions, and asked to offer explanations as to
      how they worked. Parents completed the Childhood Routines Inventory (CRI), a 19
      item parent report measure that assesses children's rituals, habits and sensory
      perceptual experiences that we have termed "compulsive-like" behavior. Results
      indicated that children's rituals and compulsions were positively related to
      their magical beliefs, and inversely related to their uses of concrete, physical
      explanations to describe various phenomena. In particular, children's beliefs
      about the effects of wishing were most consistently correlated with their
      compulsive-like rituals and routines. The findings extended the work on magical
      beliefs and obsessive-compulsive phenomena to the normative manifestation of
      compulsive behaviors found in typical development.

PMID- 12201182
TI  - An evaluation of a short questionnaire for parents about their school-aged
      children's global maturity level.
AB  - The aim was to evaluate a questionnaire for parents concerning their school-aged
      children's global maturity level. Immature children (n = 29) as reported by their
      parents were compared to a control group (n = 68). Immaturity was linked to a
      reduced general knowledge, a childish body appearance, problems with the fine
      motor function and problems with peers. The index group also had on average a
      lower test result in total score of the Wechsler Intelligence Scale for Children
      and more commission errors in the Continuous Performance Test, both test results
      indicating a lower mental age.

PMID- 12201183
TI  - The clinical course of children treated in a short-term inpatient programme.
AB  - Forty-six children admitted to short-term, usually 4-6-week child psychiatric
      inpatient treatment were evaluated from multiple perspectives on admission, at
      discharge, and at 5-month, one-year, and 3-year follow-ups. The majority of the
      patients showed an improvement in functioning over the course of the 3-year
      follow-up. However, the 3-year stability of parent, teacher and clinical ratings
      of the child was very high. Furthermore, the majority of children had a high
      level of symptoms at follow-ups. Conduct problems had the highest stability and
      predicted the poorest outcome. The results stress the importance of long-term
      follow-up of children discharged from child psychiatric tertiary services. In
      many of these cases, the problems were persistent chronic problems that require
      continued monitoring and evaluation over many years. Short-term hospitalization
      should be seen as a pathway to further assistance rather than a complete form of
      treatment.

PMID- 12201184
TI  - The paradox of the parts and the whole in understanding and improving general
      practice.

PMID- 12201185
TI  - Adverse events in surgical patients in Australia.
AB  - OBJECTIVE: To determine the adverse event (AE) rate for surgical patients in
      Australia. DESIGN: A two-stage retrospective medical record review was conducted
      to determine the occurrence of AEs in hospital admissions. Medical records were
      screened for 18 criteria and positive records were reviewed by two medical
      officers using a structured questionnaire. SETTING: Admissions in 1992 to 28
      randomly selected hospitals in Australia. STUDY PARTICIPANTS: Five hundred and
      twenty eligible admissions were randomly selected from in-patient database in
      each hospital. A total of 14,179 medical records were reviewed, with 8747 medical
      and 5432 surgical admissions. MAIN OUTCOME MEASURES: Measures included the rate
      of AEs in surgical and medical admissions, the proportion resulting in permanent
      disability and death, the proportion determined to be highly preventable, and the
      identification of risk factors associated with AEs. RESULTS: The AE rate for
      surgical admissions was 21.9%. Disability that was resolved within 12 months
      occurred in 83%, 13% had permanent disability, and 4% resulted in death.
      Reviewers found that 48% of AEs were highly preventable. The risk of an AE
      depended on the procedure and increased with age and length of stay. CONCLUSION:
      The high AE rate for surgical procedures supports the need for monitoring and
      intervention strategies. The 18 screening criteria provide a tool to identify
      admissions with a greater risk of a surgical AE. Risk factors for an AE were age
      and procedure, and these should be assessed prior to surgery. Prophylactic
      interventions for infection and deep vein thrombosis could reduce the occurrence
      of AEs in hospitals.

PMID- 12201186
TI  - Pattern of diagnostic and therapeutic care of childhood epilepsy in Alexandria,
      Egypt.
AB  - OBJECTIVES: To evaluate the quality of care delivered to children with epilepsy
      and study the predictors of seizure recurrence after initial control. DESIGN: A
      cross-sectional study was conducted during 4-month period (1 January to 30 April
      1999). SETTING: Children's hospitals providing out-patient and in-patient
      services to the majority of children in Alexandria, Egypt. OUTCOME: Seizure
      recurrence after at least 6 months from anti-epileptic drug (AED) adjustment.
      RESULTS: Electroencephalogram was performed in 82.1% of cases, whereas plasma
      assay was performed in only 7% of cases. AEDs were initiated after the first
      seizure rather than the first recurrence of seizure. Carbamazepine was the most
      frequently prescribed drug, followed by valproate, except for generalized absence
      type, which was mainly managed by valproate. Suboptimal quality of care consisted
      mainly of poor diagnostic assessment of children with epilepsy, underuse of
      plasma monitoring for AED levels, unjustified use of oral AEDs during
      breakthrough fits, and defective health education to the caregivers of children
      with epilepsy that was manifested by non-compliance with AEDs in 30.1% of cases.
      The outcome of the current healthcare was a 71.6% recurrence of seizures after
      initial control. Continuous seizures before treatment, a polytherapy regimen, and
      non-compliance with management procedures were significant predictors for seizure
      recurrence. CONCLUSIONS: More specialized neurological care and health education
      programs for the caregivers of children with epilepsy are warranted. By exploring
      the details of medical practice, a foundation is provided upon which to build a
      quality improvement program, using the parameters in our study as an initial
      framework.

PMID- 12201187
TI  - Hospital in the home is cost saving for appropriately selected patients: a
      comparison with in-hospital care.
AB  - BACKGROUND: As the cost of acute care in hospitals increases, there is an
      increasing need to find alternative means of providing acute care. Hospital in
      the home (HITH) has developed in response to this challenge. Current evidence is
      conflicting as to whether HITH provides cost savings compared with in-hospital
      care (IHC). The heterogeneous nature of HITH and the clinical complexity of
      patients is the greatest obstacle to making valid comparisons between the two
      modes of care. OBJECTIVE: To compare costs and outcomes of HITH to IHC in
      hospitals in Victoria, Australia. DATA SOURCES/STUDY SETTING: Hospital morbidity
      data and medical records from Victoria, Australia. STUDY DESIGN: A costing study
      of 924 randomly selected episodes of HITH care, individually matched to 924
      comparable IHC episodes. METHODS: Unadjusted total episode costs (TEC) and
      averaged daily costs for HITH and IHC were calculated. Mortality and length of
      stay (LOS) were compared for HITH and IHC episodes. Simple linear and multiple
      regression were used to analyse costing data, while logistic regression was used
      to compare in-hospital mortality and LOS in HITH versus IHC episodes. PRINCIPAL
      FINDINGS: The 1848 episodes of care in the sample represented a heterogeneous
      range of acute conditions in 31 Victoria hospitals. HITH consisted of two
      distinct subgroups: pure-HITH (total episode substitution) and mixed-HITH
      (partial episode substitution). The cost of episodes of acute care containing a
      HITH component were overall 9% less expensive than IHC (P = 0.04), while pure
      HITH was 38% cheaper than matched IHC (P < 0.001). The variable HITH, along with
      LOS and chemotherapy, explained the 60% variation in TEC. The mean cost of pure
      HITH episodes was 22% lower compared to mixed-HITH (P = 0.004). The in-hospital
      mortality rate in HITH (3.8%) and IHC (5.2%) was not significantly different.
      Pure-HITH was associated with shorter LOS, while mixed HITH was strongly
      associated with longer LOS. CONCLUSION: In our study the adjusted cost of HITH
      was significantly cheaper than IHC, particularly as total episode substitution.
      The cost needs to be adjusted because many factors other than HITH or IHC can
      influence crude costs. There may be potential for wider use of HITH for
      appropriately selected patients.

PMID- 12201188
TI  - Use of home health services covered by new public long-term care insurance in
      Japan: impact of the presence and kinship of family caregivers.
AB  - OBJECTIVE: In April 2000, the system for caring for the elderly in Japan was
      changed drastically with the launch of new long-term care insurance. Unlike the
      previous system, the maximum monthly amount of insured services is now decided
      solely by an applicant's physical condition, regardless of family support. We
      investigated whether the presence and kinship of a family caregiver still affect
      service use under the new system. DESIGN: A cross-sectional, mailed, self
      administered questionnaire survey and analysis using multiple logistic
      regression. SETTING: One month after the introduction of long-term care insurance
      in Japan. PARTICIPANTS: The main family caregivers of 237 applicants for long
      term care insurance with a caregiver and 33 applicants without a caregiver,
      living in the community in one city. OUTCOME MEASURES: The applicants' sex, age,
      and eligible care level, existence of a family caregiver, family caregiver's sex,
      age, and kinship, and service use for each service covered by long-term care
      insurance. RESULTS: Caregiver factors significantly affected use of the main
      services. The most popular service, nursing-home daycare, was utilized most when
      a wife was caring for her husband. As the level of care increased, this service
      was utilized less. Home help, the second most popular service, was most utilized
      when a wife was caring for her husband or when there was no caregiver.
      CONCLUSION: The use of major services may be decided more by the needs of
      caregivers than by the care level of the applicant. To successfully implement the
      new system, consideration of the caregiver situation should be included in policy
      making.

PMID- 12201189
TI  - Effectiveness of feedback to physicians in reducing inappropriate use of
      hospitalization: a study in a Spanish hospital.
AB  - OBJECTIVES: To evaluate the effectiveness of feedback to medical staff in
      reducing inappropriate hospital days, particularly those attributable to
      conservative medical discharge policies. DESIGN: Quasi-experimental pre-test/post
      test with non-equivalent control group. SETTING: A publicly funded hospital in
      industrial belt in Barcelona (Spain), serving a predominantly urban population of
      100,000. STUDY PARTICIPANTS: Two non-equivalent groups: control group (surgery
      department) and intervention group (internal medicine department). INTERVENTION:
      Meetings between hospital management and medical staff of the intervention group
      to inform clinicians of percentages and reasons for inappropriate stays in their
      departments. MAIN OUTCOME MEASURES: Total inappropriate hospital days and
      percentage attributable to physicians, measured with the Appropriateness
      Evaluation Protocol before, during, and after intervention. RESULTS: There were
      no relevant differences in the characteristics of the populations whose stays
      were reviewed during each of the periods. The total number of inappropriate stays
      and the percentage attributable to the doctor in the control group did not show
      any differences between the periods. In the intervention group, inappropriate
      stays attributable to the doctor decreased from 35.9% in the period to
      intervention to 27.7% during intervention (relative drop of 22.8%; P < 0.01), and
      rose to 32.7% after intervention. Differences in total inappropriate days were
      not significant. CONCLUSIONS: Providing physicians with feedback about percentage
      of inappropriate hospital days produced a significant reduction in the number of
      inappropriate stays attributable to the doctor, although the impact on overall
      inappropriate stays is inconclusive.

PMID- 12201190
TI  - Use of echocardiography among patients with heart failure: practice variations in
      Hungarian hospitals.
AB  - OBJECTIVE: To evaluate some factors, such as demographic factors, disease
      severity, dissemination of practice guidelines, and hospitals providing medical
      care, influencing the use of echocardiography among patients with congestive
      heart failure. DESIGN: A 'before-after' controlled epidemiological study based on
      hospital documentation. SETTING AND PARTICIPANTS: A total of 1222 admitted
      patients with a diagnosis of chronic heart failure from six voluntarily
      participating hospitals representing each level of in-patient care in Hungary.
      INTERVENTIONS: Implementation of clinical practice guidelines about heart failure
      developed by the US Agency for Health Care Policy and Research. RESULTS: The
      echocardiography was performed in slightly more than 50% of all cases in the
      total. The use of echocardiography was different according to age, sex, and
      hospitals, but no significant difference was found in disease severity and
      between the two periods of time (before and after the dissemination of the
      guidelines). CONCLUSIONS: This study reveals the existing differences in the use
      of echocardiography and the lack of essential changes after the dissemination of
      the guidelines. The distribution and implementation of guidelines needs further
      investigation.

PMID- 12201192
TI  - Qualitative research methods.
AB  - The use of rigorous qualitative research methods can enhance the development of
      quality measures, the development and dissemination of comparative quality
      reports, as well as quality improvement efforts. This paper describes how such
      methods have been and can be used, and identifies how to improve the use of such
      methods in studying quality of care. Focus groups and cognitive interviews are
      now a standard part of the development of valid and reliable survey instruments.
      They are particularly useful in developing surveys to gather data on the
      experiences and responses of patients and consumers to plans, services, and
      providers. These two methods have also been adapted and applied to improve the
      development and dissemination of comparative quality reports to consumers and
      other audiences, while key informant interviews and focus groups have been
      critical in the exploratory assessment of stakeholder responses to reports and
      their effects on consumers. Interviews have also been used to identify best
      practices found in health plans receiving high scores on the Consumer Assessment
      of Health Plans Surveys and measures of effectiveness in the Health Employer Data
      and Information Set. It would be valuable to widen the use of qualitative
      methods, especially structured observations, to document in detail the delivery
      of services designed to improve quality, so the implementation of complex
      processes can be more carefully measured and related to outcomes. The design and
      conduct of rigorous qualitative research takes a skilled and experienced team.
      Issues commonly faced in quantitative work must also be addressed in qualitative
      studies, including study design, specification of the unit of analysis, sampling,
      instrument design and administration, and, in particular, data analysis. It is
      especially critical that the analysis and interpretation process be deliberate
      and thorough to avoid the use of initial impression rather than detailed
      examination of the raw data.

PMID- 12201191
TI  - Impact of end user involvement in implementing guidelines on routine pre
      operative tests.
AB  - OBJECTIVES: To assess the impact of health professionals' involvement in the
      implementation of practice guidelines aimed at reducing the use of pre-operative
      tests in patients at low anaesthetic risk undergoing elective surgery.
      INTERVENTION: A 6 month (September 1997 to February 1998) strategy based upon
      organization of local meetings involving health professionals from six hospitals
      of Canton Ticino (Switzerland). DESIGN: Observational study (pre/post) of pre
      operative test utilization between March 1996 and December 1998. SUBJECTS AND
      METHODS: A total of 17,978 patients admitted for elective surgery over the study
      period. The latter was modelled in six intervals, three before (baseline), one
      during, and two after (adoption) guidelines implementation, respectively. For
      each time interval the proportion of patients undergoing pre-operative tests was
      estimated. Multilevel logistic regression analysis was used to assess patient
      likelihood [expressed as the odds ratio (OR)] of undergoing a diagnostic test in
      each period, using the implementation interval as the reference category. MAIN
      OUTCOME MEASURE: Change in patient probability of undergoing pre-operative tests
      in the adoption interval. RESULTS: Adoption of the recommendations was associated
      with 81% [OR = 0.19; 95% confidence interval (CI) 0.15-0.23] reduction of patient
      probability of undergoing coagulation test, 73% (OR = 0.27; 95% CI 0.23-0.33) for
      glycaemia, 62% (OR = 0.38; 95% CI 0.33-0.44) for azotaemia, 57% (OR = 0.43; 95%
      CI 0.36-0.51) for chest X-ray, 49% (OR = 0.51; 95% CI 0.44-0.60) for creatinemia,
      and 43% (OR = 0.57; 95% CI 0.48-0.69) for ECG. Overall, these findings
      corresponded to a cost saving of 67,890 Swiss francs (US$42,000) for the last
      quarter under study. CONCLUSIONS: This study indicates that an implementation
      strategy based upon direct involvement of end users in the identification of
      possible barriers to change can be successful in promoting the use of practice
      guidelines.

PMID- 12201193
TI  - Natural frequencies and the representation of risk.

PMID- 12201194
TI  - Prediction of the bioaccumulation of persistent organic pollutants in aquatic
      food webs.
AB  - Predictive correlations of the bioaccumulation factor of persistent organic
      pollutants in aquatic biota are presented as functions of their octanol/water
      partition coefficient. The correlations demonstrate the importance of
      differentiating among the different levels in the food web and of accounting for
      the pollutant's bioavailability by considering the amount freely dissolved in
      water instead of the total concentration. They also reveal the significance of
      the pollutant's octanol/water partition coefficient value on its biomagnification
      along the levels of the trophic chain. Prediction results, finally, demonstrate
      that the correlations provide reasonably accurate estimates of bioaccumulation,
      typically within an order-of-magnitude.

PMID- 12201195
TI  - Metal accumulation in aquatic macrophytes from southeast Queensland, Australia.
AB  - To determine the extent of metal accumulation in some aquatic macrophytes from
      contaminated urban streams in southeast Queensland, plants were sampled from six
      sites, along with contiguous sediments. In all, 15 different species were
      collected, the most common genera being Typha (Cattails or Bulrushes) and
      Persicaria (Knotweeds). Before heavy metal analysis, plants were further
      separated into various morphological tissues, and five selected samples were
      separated into various physiological tissues. The cadmium, copper, lead and zinc
      content of the plants were analysed using flames AAS. In general, plant roots
      exhibited higher metal concentrations than the contiguous sediments. Of the
      metals of interest, only for zinc was there a relatively clear pattern of
      increasing accumulation in aquatic macrophytes with increasing sediment metal
      concentrations. Comparison between morphological tissues of the sampled plants
      found that roots consistently presented higher metal concentrations than either
      the stems or leaves, however unlike previous studies, this investigation revealed
      no consistent trend of stems accumulating more metals than the leaves. For Typha
      spp., metal concentrations followed the order of roots > rhizomes > leaves, while
      for Persicaria spp. the order was roots > leaves > stems. The submerged species
      Myriophyllum aquaticum accumulated the highest levels of metals overall (e.g. Zn
      4300 micrograms g-1 dry weight and Cd 6.5 micrograms g-1), and the emergent
      macrophytes also exhibited relatively high metal contents in their roots. The
      leaves of the submerged and floating-leafed species collected contained
      relatively high quantities of the four metals of interest, compared with the
      leaves of emergent aquatic macrophytes. In the Typha rhizome and Persicaria stem
      samples analysed for internal variation in metal content, there was a pattern of
      increasing metal concentrations towards the external sections of the stem, both
      for subterranean stems (rhizomes) and above-substrate stems. For Persicaria
      stems, no clear pattern was observed for cadmium and lead, the two metals
      investigated that are not required by plants for survival.

PMID- 12201196
TI  - Adsorption and desorption of cadmium by goethite pretreated with phosphate.
AB  - The adsorption of Cd by oxides or soils have been extensively studied, however,
      the desorption has received relatively limited attention, especially in the
      presence of phosphate. In this study, a batch equilibration method was used to
      investigate Cd sorption and desorption by goethite pretreated with phosphate.
      Phosphate not only enhanced Cd adsorption, but also accelerated the adsorption
      process. Compared with Cd adsorption by goethite alone, phosphate substantially
      moved the adsorption curves (edges) to lower pH range, indicative of enhancement
      of Cd sorption. The Cd adsorption by the pretreated goethite reached apparent
      equilibrium within 24 h at 20 degrees C, while such equilibrium was not observed
      after 4 weeks in the absence of phosphate. Cadmium was more readily released from
      phosphate-treated goethite. It is believed that phosphate blocked the pores on
      goethite surface, which lead to the fast adsorption kinetics and high extraction
      percentage. These results provided strong support for the diffusion of Cd into
      goethite particles.

PMID- 12201197
TI  - Levels of cadmium and zinc in hepatopancreas of reared Mytilus galloprovincialis
      from the Gulf of Trieste (Italy).
AB  - Cadmium and zinc concentrations were determined in hepatopancreatic tissues of
      Mytilus galloprovincialis, reared in three non-contaminated hatcheries of the
      Gulf of Trieste (Northern Adriatic Sea). Mussels were collected in 13 sampling
      exits with monthly frequency for verifying possible seasonal variations. Freeze
      dried hepatopancreatic tissues were dissolved by nitric acid procedure using a
      microwave system; analysis of Zn and Cd followed by AAS technique. Metal
      concentrations were below the critical values for mollusc soft tissues, but
      xenobiotic cadmium had values requiring monitoring attention. Cadmium and zinc
      showed moderate variations along the months, with a slight winter maximum
      followed by a summer pre-spawning minimum, matching the seasonal trends of
      temperature/salinity. The estuarine site appears to have the best quality of the
      examined area in terms of metal contents. The results can constitute a guideline
      for the water quality in the Northern Adriatic Sea, and permit comparisons with
      the quality of other areas of the Mediterranean Sea.

PMID- 12201198
TI  - Soil phosphorus quantity-intensity relationships to predict increased soil
      phosphorus loss to overland and subsurface flow.
AB  - Soil phosphorus (P) quantity-intensity (q-i) relationships, based on common
      extraction methods, may potentially be used to estimate the risk of P loss in
      overland flow and subsurface drainage water. Some workers have used nonlinear q-i
      relationships to derive thresholds in soil test P (STP; a quantity factor) above
      which the risk of P loss increases, while others find linear relationships and no
      threshold. We present here a simple modelling exercise (based on Langmuir
      adsorption theory) along with data from literature to explain the behaviour of q
      i relationships, and to give an explanation for this apparent discrepancy. The
      data indicate that q-i relationships are dependent upon the soil to solution
      ratio of the P intensity parameter, adsorption capacity (Qmax) and strength (K)
      of the soil, and the total range in STP. In turn, this affects the calculation of
      a threshold in STP. The q-i relationship tends towards linearity under conditions
      of a narrow total range of STP and/or when using a wide soil to solution ratio
      for estimating the P intensity parameter. Under such conditions, a threshold is
      difficult to detect, and uncertain. We conclude that the sensitivity of
      thresholds to experimental conditions and soils needs to be considered if
      thresholds are to be successful in environmental management to decrease P loss to
      surface waters.

PMID- 12201199
TI  - Measurements of PM10 and PM2.5 in urban area of Nanjing, China and the assessment
      of pulmonary deposition of particle mass.
AB  - Measurement of PM10 and PM2.5 was carried out at six sites of Nanjing, China in
      the period of February-May 2001. The pH and conductivity of water-soluble matter
      of PM10 and PM2.5 were determined, and the samples were analyzed for total carbon
      (TC), organic carbon (OC) and inorganic carbon (IC) of the water-soluble
      fraction. The distribution of aerosol mass concentration in size was also
      measured at one site SB by a nine-stage impactor followed to assess the pulmonary
      deposition of particles in different tracts of the human respiratory system.
      Compared with National Ambient Air Quality Standard (NAAQS) of the USA, the level
      of PM10 and PM2.5 in Nanjing was much higher. Especially for site SY, the average
      particle mass concentrations (774.5 micrograms/m3 for PM10 and 481.4
      micrograms/m3 for PM2.5) were more than five times the NAAQS standard. At site SB
      aerosol mass distribution in size had shown the similar characteristics with
      accumulation (Dp < 1 micron) and coarse (Dp > 1 micron) modes. More than 70% of
      total suspended particles is of a size that they are deposited in the respiratory
      tract below trachea, whereas about 22% of the mass is respirable and will reach
      the alveoli. Water-soluble fractions of PM10 and PM2.5 in Nanjing are acidic, and
      the pH of PM2.5 is lower than that of PM10. OC makes up the majority of TC and
      accounts for 3-14% of mass concentration of PM10 and/or PM2.5, while IC only
      accounts for 0.1-0.5% of PM10 and/or PM2.5 mass.

PMID- 12201200
TI  - Atmospheric phase distribution of oxidized and reduced nitrogen at a forest
      ecosystem research site.
AB  - Atmospheric concentrations of gaseous NH3 and HNO3 and of particulate NH4+ and
      NO3- were measured during various seasons at a forest ecosystem research site in
      the "Fichtelgebirge" mountains in Central Europe. Air masses arriving at this
      site were highly variable with respect to trace compound concentration levels and
      their concentration ratios. However, the distributions of NH4+ and NO3- within
      the aerosol particle size spectra exhibited some very consistent patterns, with
      the former dominating the fine particle concentrations, and the latter dominating
      the coarse particles range, respectively. Overall, the particulate phase (NH4+ +
      NO3-) dominated the atmospheric nitrogen budget (particulate and gas phase, NH4+
      + NO3- + NH3 + HNO3) by more than 90% of the median total mixing ratio in winter,
      and by more than 60% in summer. The phase partitioning varied significantly
      between the winter and summer seasons, with higher relative importance of the
      gaseous species during summer, when air temperatures were higher and relative
      humidities lower as compared to the winter season. Reduced nitrogen dominated
      over oxidized nitrogen, indicating the prevailing influence of emissions from
      agricultural activity as compared to traffic emissions at this mountainous site.
      A model has been successfully applied in order to test the hypothesis of
      thermodynamic equilibrium between the particulate and gas phases.

PMID- 12201201
TI  - Studies of 3D-quantitative structure-activity relationships on a set of
      nitroaromatic compounds: CoMFA, advanced CoMFA and CoMSIA.
AB  - By using comparative molecular field analysis (CoMFA), advanced CoMFA and
      comparative molecular similarity index analysis (CoMSIA) methods, the 3D
      relationships between the structures of 35 nitroaromatic compounds and their
      toxicities have been investigated to yield statistically reliable models of
      considerable predictive power. In contrast to CoMFA, CoMSIA produces better
      results for the correlation. Moreover, the obtained CoMSIA contour maps that
      interpret the correlations in terms of field contributions allow physicochemical
      properties relevant for binding to be easily mapped back onto molecular
      structures, and thus elucidate structural features among ligands that are
      responsible for toxicities. Besides, most of the highlighted regions in CoMSIA
      and CoMFA contour maps are mirrored by features in the surrounding environment.
      Thereby, CoMFA and CoMSIA both help to give explanations of the toxic mechanism
      of tested compounds.

PMID- 12201202
TI  - Anaerobic biodegradation of polycyclic aromatic hydrocarbon in soil.
AB  - Known concentrations of phenanthrene, pyrene, anthracene, fluorene and
      acenapthene were added to soil samples to investigate the anaerobic degradation
      potential of polycyclic aromatic hydrocarbon (PAH). Consortia-treated river
      sediments taken from known sites of long-term pollution were added as inoculum.
      Mixtures of soil, consortia, and PAH (individually or combined) were amended with
      nutrients and batch incubated. High-to-low degradation rates for both soil types
      were phenanthrene > pyrene > anthracene > fluorene > acenaphthene. Degradation
      rates were faster in Taida soil than in Guishan soil. Faster individual PAH
      degradation rates were also observed in cultures containing a mixture of PAH
      substrates compared to the presence of a single substrate. Optimal incubation
      conditions were noted as pH 8.0 and 30 degrees C. Degradation was enhanced for
      PAH by the addition of acetate, lactate, or pyruvate. The addition of municipal
      sewage or oil refinery sludge to the soil samples stimulated PAH degradation.
      Biodegradation was also measured under three anaerobic conditions; results show
      the high-to-low order of biodegradation rates to be sulfate-reducing conditions >
      methanogenic conditions > nitrate-reducing conditions. The results show that
      sulfate-reducing bacteria, methanogen, and eubacteria are involved in the PAH
      degradation; sulfate-reducing bacteria constitute a major component of the PAH
      adapted consortia.

PMID- 12201203
TI  - Adsorption of propisochlor on soils and soil components equation for multi-step
      isotherms.
AB  - Static equilibrium measurements were performed for the study of propisochlor on
      three different kinds of soils at pH = 7.0 at 25 degrees C. The concentration of
      herbicide was changed from 30 to 300 mumol/l. The obtained two-step adsorption
      isotherms cannot be evaluated by using the Freundlich or Langmuir equations. New
      equation has been derived by making use of the usual mass balance and equilibrium
      relationships of the adsorption and by considering the possibility of the
      formation of associates of the hydrophobic solute molecules. The characteristic
      model parameters of each step of the adsorption isotherm were estimated for the
      studied systems by a non-linear least square regression. The calculated curves
      fit well to the experimentally obtained two-step isotherms and the parameters of
      the model can be used for the characterization of the pesticide-soil interactions
      and consequently the mobility of the propisochlor in soil/water systems.

PMID- 12201204
TI  - Long-term assessment of the wet precipitation chemistry in Austria (1984-1999).
AB  - The aim of the present study was to determine the long-time trends in
      concentrations and depositions of major ions in wet precipitation samples
      collected at 11 sampling sites from the Austrian precipitation chemistry network
      in the period 1984-1999. The analytical results were treated by the use of least
      square linear regression method. It is shown that a serious decrease of sulfate
      (between 30% and 60% for the period) and hydrogen ion (between 60% and 102% for
      the period) concentrations and depositions is achieved at almost all sampling
      sites and in most of these cases the linear trend proves to be statistically
      significant. Nitrogen containing ions and base cations do not reveal a distinct
      trend of changing and in the majority of the sites the linear models are not
      adequate. In principle, an overall slight concentration and deposition decrease
      for these major ions is observed (up to 30% for the period of observation) but
      some substantial exceptions are also found (site Haunsberg or site Lobau). The
      changes in chloride concentration and deposition, too, do not indicate
      significant linear trend and, in general, are decreasing for the period of
      monitoring. In order to give some explanation of the exceptional behaviour of
      some of the major ions in several sites, an additional comparison with Austrian
      emission data (sulfur dioxide, nitrogen oxides, ammonium) and with data from five
      EMEP sites from neighbouring countries is performed. A significant West-East
      trend of acidity increase is found as well as a good correlation with the
      emission trends. Therefore, both transboundary and specific local factors could
      be substantial factors in the wet precipitation chemistry in the region.

PMID- 12201205
TI  - Preliminary report on the levels of elements in four fish species from the
      Arabian Gulf of Saudi Arabia.
AB  - This manuscript presents preliminary information on the concentrations of heavy
      metals: cadmium, lead, nickel, vanadium and arsenic in 66 fish samples of four
      different species collected from three different sites on the Gulf coast of Saudi
      Arabia where there are agricultural, municipality and petroleum industrial
      activities. Fish species; highly consumed by the local population were selected:
      Emperors, Rabbitfish, Doublebar-bream and Greasy-grouper to ascertain the fish
      quality for human consumption. The concentration of metals was determined by
      atomic absorption spectrophotometry (AA). The average mean concentrations (ng/g
      wet wt.) of cadmium, lead, nickel, vanadium and arsenic in fish tissues were as
      follows: 4.6 +/- 7.2, 20.0 +/- 20.8, 60.6 +/- 63.2, 73.6 +/- 27.1 and 42.7 +/-
      17.4 ng/g wet wt. respectively. The concentration of metals was significantly
      affected by the sampling site and fish species. In Maniefa site, the
      concentrations of all tested metals were higher than in Al-Dammam and Dareen
      sites with the exception of nickel where no significant differences were found.
      Levels of cadmium, lead, nickel, vanadium and arsenic varied depending on the
      fish species. The concentration of metals was below the maximum allowed limit by
      the Saudi and international legislations for fish human consumption permissible
      limit.

PMID- 12201206
TI  - Temperature dependence of Henry's law constant in an extended temperature range.
AB  - The Henry's law constants H for chloroform, 1,1-dichloroethane, 1,2
      dichloropropane, trichloroethene, chlorobenzene, benzene and toluene were
      determined by the EPICS-SPME technique (equilibrium partitioning in closed
      systems--solid phase microextraction) in the temperature range 275-343 K. The
      curvature observed in the ln H vs. 1/T plot was due to the temperature dependence
      of the change in enthalpy delta H0 during the transfer of 1 mol solute from the
      aqueous solution to the gas phase. The nonlinearity of the plot was explained by
      means of a thermodynamic model which involves the temperature dependence of delta
      H0 of the compounds and the thermal expansion of water in the three-parameter
      equation ln (H rho TT) = A2/T + BTB + C2, where rho T is the density of water at
      temperature T, TB = ln(T/298) + (298-T)/T, A2 = -delta H298(0)/R, delta H298(0)
      is the delta H0 value at 298 K, B = delta Cp0/R, and C2 is a constant. delta Cp0
      is the molar heat capacity change in volatilization from the aqueous solution. A
      statistical comparison of the two models demonstrates the superiority of the
      three-parameter equation over the two-parameter one ln H vs. 1/T). The new, three
      parameter equation allows a more accurate description of the temperature
      dependence of H, and of the solubility of volatile organic compounds in water at
      higher temperatures.

PMID- 12201207
TI  - Insights into molecular pathogenesis of type 2 diabetes from knockout mouse
      models.

PMID- 12201208
TI  - Familial isolated growth hormone deficiency: genetics and pathophysiology.

PMID- 12201209
TI  - Hepatocyte growth factor as cardiovascular hormone: role of HGF in the
      pathogenesis of cardiovascular disease.
AB  - Hepatocyte growth factor (HGF) is a mesenchyme-derived pleiotropic factor which
      regulates cell growth, cell motility, and morphogenesis of various types of
      cells, and is thus considered a humoral mediator of epithelial-mesenchymal
      interactions responsible for morphogenic tissue interactions during embryonic
      development and organogenesis. Although HGF was originally identified as a potent
      mitogen for hepatocytes, HGF has also been identified as a member of angiogenic
      growth factors. Interestingly, the presence of its specific receptor, c-met, is
      observed in vascular cells, endothelial cells and cardiac myocytes. In addition,
      the mitogenic action of HGF on human endothelial cells was most potent among
      growth factors. Recent studies have demonstrated the potential application of HGF
      to treat cardiovascular disease such as peripheral vascular disease, myocardial
      infarction and restenosis after angioplasty. On the other hand, serum HGF
      concentration was significantly correlated with blood pressure. These results
      suggest that HGF secretion might be elevated in response to high blood pressure
      as a counter-system against endothelial dysfunction, and may be considered as an
      index of severity of hypertension. In this review, we discussed the potential
      role of HGF in cardiovascular disease.

PMID- 12201210
TI  - Comparison of ACTH secretion in Cushing's adenoma and clinically silent
      corticotroph adenoma by cell immunoblot assay.
AB  - Immunocytochemical staining and cell immunoblot assay (CIBA) were performed in
      adenoma tissue from five patients with Cushing's disease and three patients with
      clinically silent corticotroph adenomas. All five patients with Cushing's disease
      showed hypersecretion of ACTH (130, 190, 331, 120, and 130 pg/ml), high levels of
      serum cortisol (26.6-44.0 micrograms/dl), and symptoms of Cushing's disease. All
      three patients with silent corticotroph adenoma showed hypersecretion of ACTH
      (110, 140, and 160 pg/ml) and normal levels of serum cortisol (11.4-26.8
      micrograms/dl). The size of the pituitary adenoma on magnetic resonance imaging
      was smaller in patients with Cushing's disease (mean 8.2 mm) than in patients
      with silent corticotroph adenoma (mean 26.7 mm) (p = 0.001). Transsphenoidal
      surgery was performed to totally resect the adenoma tissue. Immunostaining for
      ACTH showed diffuse ACTH-immunopositive cells in all eight adenomas. CIBA
      technique showed a good correlation between percentage of ACTH-immunopositive
      cells and level of plasma ACTH in patients with Cushing's disease but no
      correlation between the two parameters in patients with silent corticotroph
      adenoma. The percentage of ACTH-secreting cells and the amount of hormone
      secreted by a single cell are too low in silent corticotroph adenomas to cause an
      increase in plasma ACTH level corresponding to the large tumor size.

PMID- 12201211
TI  - Clinical utility of thyroid ultrasonography in the diagnosis of congenital
      hypothyroidism.
AB  - To determine the clinical utility of thyroid ultrasonography in the diagnosis of
      congenital hypothyroidism (CH) before initiation of therapy, ultrasonographic
      images of the thyroid gland with a high-resolution transducer were obtained in
      204 healthy infants aged from newborn to 12 months (Group A), and 174 infants
      suspected of having CH detected by neonatal mass screening (Group B). The thyroid
      gland was imaged by transverse scanning at the anatomic site of the thyroid
      gland. The maximal width of thyroid on the transverse section in the normal
      location was measured. By comparing with the normal thyroid gland size and
      location obtained from Group A, 174 infants of Group B were divided into four
      subgroups: 1) Normal in size (n = 117), 2) Enlarged (n = 33), 3) Small (n = 1)
      and 4) Invisible in the normal location (n = 23). They were compared with the
      final diagnoses based on the results of chemical laboratory data and
      scintigraphic findings. The sensitivity and the specificity for the presence or
      absence of the thyroid gland in the normal location were 96% (22/23) and 99%
      (150/151), respectively. Both subgroups of normal and enlarged sized gland
      included healthy infants (false positive), transient hyperthyrotropinaemia,
      transient hypothyroidism and CH due to dyshormonogenesis. We conclude that
      ultrasonography is useful for determining the presence or absence of the thyroid
      gland in the normal location, whereas normal and enlarged sized glands require
      further examination to complete the diagnosis.

PMID- 12201212
TI  - Implication of maternal nitrogen balance in the regulation of circulating levels
      of insulin-like growth factor-I in human pregnancy.
AB  - Nutrition plays an important role in regulating the circulating levels of insulin
      like growth factor-I (IGF-I). We have demonstrated that reduced nitrogen balance
      is related to changes in serum IGF-I levels but not serum growth hormone levels
      in pregnant rats. In the present study, we investigated the effects of changes in
      nitrogen balance on serum IGF-I levels in normal and malnourished pregnant women
      (defined as having negative nitrogen balance). Forty-eight pregnant women
      (threatened miscarriage and premature labor, 39; pre-eclampsia, 3; hyperemesis,
      3; ileus, 2; bleeding from the colon, 1) and 19 non-pregnant women admitted in
      Kobe University Hospital were enrolled in this study. Blood samples of normal
      pregnant controls were also obtained from 172 healthy pregnant women attending
      the outpatient clinic. Serum IGF-I levels and nitrogen balance were measured
      serially in 9 pregnant women with threatened miscarriage and premature labor and
      9 malnourished pregnant women out of 48 pregnant women. Serum IGF-I and urinary
      nitrogen levels were measured by radioimmunoassay with acid-ethanol extraction
      and the Dumas method, respectively. Nitrogen balance was expressed as the
      difference between daily nitrogen intake and nitrogen excretion assessed by
      urinary nitrogen levels. Serum IGF-I levels in normal pregnant controls
      significantly increased in the third trimester of pregnancy compared with non
      pregnant controls. No difference in serum IGF-I levels in any trimester of
      pregnancy was observed between normal pregnant controls and pregnant women with
      threatened miscarriage and premature labor. There was no significant difference
      in nitrogen balance between the pregnant women with threatened miscarriage and
      premature labor and non-pregnant controls. In the longitudinal study, no
      correlation was found between the changes in serum IGF-I levels and those in
      nitrogen balance in the 9 pregnant women with threatened premature labor (daily
      nitrogen balance > 0 g/day) on the basis of linear regression analysis. On the
      other hand, the changes in serum IGF-I levels in the 9 malnourished pregnant
      women were significantly correlated with those in nitrogen balance (y = 1.72x +
      17.5; r = 0.60; P < 0.05: linear regression analysis). These results indicate
      that maternal nutritional states have a major effect on serum IGF-I levels in
      malnourished pregnant women, but not in pregnant women with daily nitrogen
      balance > 0 g/day. Serum IGF-I levels can be a potent index of nutritional states
      under malnutrition during human pregnancy.

PMID- 12201213
TI  - Is antithyroid treatment really relevant for young patients with subclinical
      hyperthyroidism?
AB  - This study investigated whether symptoms and findings of hyperthyroidism exist in
      patients with subclinical hyperthyroidism (SCH) and sought to determine whether
      hyperthyroidism treatment improves them. Twenty patients (mean age: 36.10 +/-
      1.41 years) and 20 healthy controls [mean age: 36.35 +/- 1.50 years) were
      included in the study. The SCH duration of patients was at least 6 months. Bone
      mineral density (BMD) was measured in both patients and controls. The patients
      were randomly divided into 2 groups of 10 patients each. Symptoms and findings of
      hyperthyroidism were evaluated and BMD, 24 hour ambulatory blood pressure, holter
      measurements and serum lipids were determined initially in both groups and 6
      months after the attainment of euthyroidism in the treatment group (Group 1) and
      after a 6 months follow-up in the observation group (Group 2). In the patient
      group, BMD showed a decrease of 1.3% and 3.9% in femur neck and L1-4 vertebra
      compared with controls, respectively. But there was no difference in BMD between
      patients and controls. Fatigue, nervousness, over sweating, tachycardia and
      tremor improved with treatment. The number of patients with fatigue, nervousness,
      over sweating and tachycardia increased in Group 2 after the observation. There
      was no difference between initial values and after a 6 month period from
      observation or on attainment of euthyroidism in the values of BMD, lipids,
      minimal and maximal heart rate, total number of ventricular and supraventricular
      beats and heart rate variability. As a result symptoms of hyperthyroidism were
      found to be increased in SCH but they partly decreased after antithyroid
      treatment. But no favourable effects of antithyroid treatment on BMD, heart rate
      and arrhythmia incidence were found in young, premenopausal patients with SCH
      during the 6 month period.

PMID- 12201214
TI  - Acute pancreatitis, hepatic cholestasis, and erythema nodosum induced by
      carbimazole treatment for Graves' disease.
AB  - A 33-year old female was diagnosed as Graves' disease and started on carbimazole.
      One month later when she was already euthyroid only on carbimazole therapy, she
      developed acute pancreatitis associated with mild cholestatic hepatitis and
      erythema nodosum. Carbimazole therapy was interrupted, pancreatic and liver
      function gradually improved and became normalized two weeks later. Other
      potential etiological causes of acute pancreatitis, hepatitis and erythema
      nodosum were excluded. Rechallenge with a single dose of carbimazole led to a new
      episode of acute pancreatitis and cholestatic hepatitis one day later. The
      appearance of different hypersensitivity reactions including pancreatitis,
      hepatitis and erythema nodosum, together with the observation that the interval
      between drug intake and onset of symptoms became shorter with repeated exposure
      to carbimazole, point to an immune-mediated mechanism. Carbimazole has to be
      added to the list of drugs capable of inducing acute pancreatitis, and should be
      emphasized the need to discontinue this medication as soon as there is evidence
      of pancreatic dysfunction.

PMID- 12201215
TI  - Fulminant diabetes mellitus associated with pregnancy: case reports and
      literature review.
AB  - We report two cases of type 1 diabetes mellitus fulminantly developed as diabetic
      ketoacidosis (DKA) at 19 weeks of gestation and immediately after delivery.
      Development of type 1 diabetes around pregnancy is not rare, but its fulminant
      development is highly uncommon. We also review the relevant literature concerning
      mostly Japanese cases. In our cases, the group of patients with fulminant
      progressive diabetes mellitus associated with pregnancy required insulin
      replacement therapy even after the acute period and showed high value of
      pancreatic exocrine enzymes, i.e. amylase, elastase, and lipase. The phenotype of
      this group was similar to "nonautoimmune, fulminant type 1 diabetes" described by
      Imagawa et al., where the laboratory data of type 1 diabetes-related
      autoantibodies showed negative. It is well known that autoimmune diseases are in
      good control during pregnancy. Our present finding suggests that this type of
      fulminant type 1 diabetes mellitus associated with pregnancy might develop as a
      consequence of a nonautoimmune mechanism.

PMID- 12201216
TI  - Effect of pioglitazone on blood proinsulin levels in patients with type 2
      diabetes mellitus.
AB  - The objective of this study was to clarify the influence of pioglitazone (Pio) on
      proinsulin (PI) in patients with type 2 diabetes mellitus. The subjects were 55
      patients with type 2 diabetes. Among them, 18, 18, and 19 patients were
      respectively treated with Pio alone (group P), gliclazide (Gli) alone (group G),
      or Pio plus Gli (group PG) for 12 weeks. Fasting blood samples were obtained
      before and after treatment and were used to measure fasting plasma glucose (FPG),
      HbA1C, immunoreactive insulin (IRI), and PI. The levels of FPG, HbA1C, and IRI
      showed a significant decrease after treatment with Pio in groups P and PG.
      Treatment with Pio also caused PI to decrease significantly (group P: from 24.7
      +/- 12.9 (mean +/- SD) to 14.0 +/- 6.2 pmol/L, p < 0.01, group PG: from 24.3 +/-
      11.3 to 14.4 +/- 6.5 pmol/L, p < 0.01). In group G, treatment with Gli caused FPG
      and HbA1C to decrease significantly, but PI showed no change (21.5 +/- 12.3 to
      21.6 +/- 10.4 pmol/L, p = n.s.). In patients with type 2 diabetes, treatment with
      Pio achieved an improvement of glycemic control and reduced the load on the
      pancreatic beta cells.

PMID- 12201217
TI  - Prevalence of serum anti-myeloperoxidase antineutrophil cytoplasmic antibodies
      (MPO-ANCA) in patients with Graves' disease treated with propylthiouracil and
      thiamazole.
AB  - Patients with Graves' disease (n = 61) treated with propylthiouracil (PTU) or
      thiamazole (MMI) were studied retrospectively to investigate differences in the
      prevalence of anti-myeloperoxidase anti-neutrophil cytoplasmic antibodies (MPO
      ANCA) in relation to treatment with anti-thyroid drugs. The patients were divided
      into two groups: PTU-treated group (n = 32) and MMI-treated group (n = 29). There
      were no significant differences between the two groups in terms of age, gender
      distribution, or duration of treatment. In the PTU group, 8/32 (25%) patients
      were positive for MPO-ANCA, whereas in the MMI group, 1/29 (3.4%) patients were
      positive. There were no significant differences in age, duration, or dosage
      between the MPO-ANCA positive and negative patients. Most of the MPO-ANCA
      positive patients were asymptomatic, except for two patients in whom rheumatic
      arthritis or membranous glomerulonephritis developed. None of the MPO-ANCA
      positive patients were diagnosed as having classical ANCA-associated vasculitis.
      Thus, there is a high frequency of MPO-ANCA in patients with Graves' disease
      treated with PTU, compared with patients treated with MMI, although classical
      ANCA-associated vasculitis develops in only a few MPO-ANCA positive patients.

PMID- 12201218
TI  - Autocrine/paracrine involvement of parathyroid hormone-related peptide in
      vascular leiomyoma.
AB  - Vascular leiomyomas are believed to arise from the smooth muscle of blood vessels
      and are characterized by the proliferation of vascular smooth muscle cells (VSMC)
      and numerous slit-like vascular lumens. Parathyroid hormone (PTH)-related peptide
      (PTHrP) plays an important role in local autocrine and/or paracrine regulation of
      cellular growth and function in VSMC. To investigate the interaction between VSMC
      and endothelial cells, we evaluated the distribution of PTHrP and PTH/PTHrP
      receptor in 10 vascular leiomyomas of the skin by immunohistochemistry and in
      situ hybridization (ISH) of paraffin-embedded specimens. Both
      immunohistochemistry and ISH revealed that PTH/PTHrP-receptors are expressed in
      endothelial cells lining areas with slit-like vascular lumens and very weakly
      expressed in proliferating VSMC in all vascular leiomyomas. On the other hand,
      PTHrP itself was localized mainly in proliferating VSMC. These results support
      the hypothesis that PTHrP acts through the PTH/PTHrP-receptor via an autocrine
      and/or paracrine mechanism from VSMC to endothelial cells in the formation of
      characteristic microenvironments of vascular leiomyoma cell composition.

PMID- 12201219
TI  - Circulating nuclear matrix protein in Graves' disease.
AB  - The Fas/Fas ligand system induces apoptosis, while soluble Fas (sFas) blocks the
      system and soluble Fas ligand (sFasL) functions to induce apoptosis. The assay of
      nuclear matrix protein (NMP) released from dead or dying cells can be used to
      quantitate cell death. Therefore, we evaluated the relationship among serum
      levels of NMP, sFas, and sFasL in patients with Graves' disease. We measured
      serum levels of sFas, sFasL, NMP, thyroid hormones and TSH receptor antibody in
      20 normal control subjects (5 men, 15 women; mean age, 44.3 years), 32 patients
      with untreated Graves' disease (4 men, 28 women; mean age, 44.1 years), and 10
      patients with Graves' disease treated by methimazole (3 men, 7 women; mean age
      39.2 years). Serum NMP was significantly lower (10.4 +/- 4.3 IU/ml, p < 0.02) in
      patients with untreated Graves' disease than in patients with treated Graves'
      disease (16.4 +/- 7.3 IU/ml) and control subjects (15.3 +/- 8.9 IU/ml). Serum
      sFas and sFasL were significantly higher in patients with untreated Graves'
      disease than in patients with treated Graves' disease and in control subjects. In
      the patient groups with Graves' disease, serum NMP was negatively correlated with
      sFas (r = -0.612, p < 0.001) and serum sFas was positively correlated with FT4 (r
      = 0.360, p < 0.05) and TRAb (r = 0.384, p < 0.05). Serum NMP was correlated with
      sFas. These results suggest that serum NMP is decreased in patients with
      untreated Graves' disease, and that cell death or apoptosis in patients with
      Graves' disease is affected by soluble Fas under the influence of thyroid
      function.

PMID- 12201220
TI  - Immunohistochemical localization of growth factor-regulated channel (GRC) in
      human tissues.
AB  - Insulin-like growth factor-I activates a calcium-permeable cation channel GRC
      (growth factor-regulated channel). In the present study, we investigated the
      immunohistochemical localization of GRC in human tissues using a polyclonal anti
      GRC antibody. Immunoreactive GRC was detected in the stomach, duodenum, large
      intestine and prostate. In these tissues, GRC-expressing cells were distributed
      solitarily in the epithelium and coexpressed chromogranin-A, a marker of
      neuroendocrine cells. GRC was also expressed in the epithelium of the pancreatic
      duct, mammary gland, parotid gland, and submandibular gland. Epithelial cells of
      the renal tubule and the tracheal gland were also stained with anti-GRC antibody.
      In the lung, alveolar macrophages expressed GRC. In the brain, Purkinje cells of
      the cerebellum and arachnoid cells of the meningitis expressed GRC. These results
      indicate that GRC is expressed in restricted types of cells in particular
      tissues, and that GRC may modulate calcium entry in these cells.

PMID- 12201221
TI  - Adrenal influence on the persistence of pseudopregnancy in rats.
AB  - The effect of adrenalectomy on the duration of pseudopregnancy was investigated
      in rats. When adrenalectomy was performed three days before cervical stimulation
      or when it was done on the first day (day 1, day of estrus) or day 2 of
      pseudopregnancy, the duration of the pseudopregnancy was significantly prolonged
      (3.0, 2.5 and 1.8 days respectively). This effect of adrenalectomy was not seen
      when operation was delayed until day 4 of pseudopregnancy. Adrenalectomy on day 2
      of pseudopregnancy significantly increased prolactin (PRL) release at the time of
      the nocturnal PRL surge (5:00) on day 7. When rats were ovariectomized
      simultaneously with adrenalectomy on day 1, the stimulating effect of
      adrenalectomy on PRL release was more evident. The effect of active immunization
      against corticosterone on the continuation of pseudopregnancy was also examined.
      Neutralization of plasma corticosterone extended the duration of pseudopregnancy
      and the binding activity of the antiserum positively correlated with the length
      of continuing diestrus (P < 0.05). These results indicate the negative effect of
      the adrenal glands, which is probably due to corticosterone, on PRL release in
      pseudopregnant rats and that the early relief of this inhibition extends the
      duration of pseudopregnancy.

PMID- 12201222
TI  - Time-dependent effects of vitamin K2 (menatetrenone) on bone metabolism in
      postmenopausal women.
AB  - Vitamin K is known to mediate carboxylation of glutamyl residues of osteocalcin.
      We evaluated the effects of vitamin K2 (menatetrenone) treatment (45 mg/day) for
      48 weeks on the markers of bone formation and resorption, bone mineral density
      (BMD), and the incidence of vertebral fractures in 34 Japanese postmenopausal
      women (aged 48-82 years). Serum levels of alkaline phosphatase (ALP) increased
      gradually and became significant at 48 weeks after menatetrenone treatment, while
      urinary excretion of deoxypyridinoline (DPD) decreased transiently but
      significantly at 4 weeks. Serum levels of both intact osteocalcin (OC) and
      carboxylated OC (Gla-OC) increased rapidly and significantly within 4 weeks and
      sustained their high values up to 48 weeks after the treatment, while those of
      undercarboxylated OC (Glu-OC) decreased reciprocally. These results can be
      interpreted to suggest that Glu-OC was converted to Gla-OC in vivo. On the other
      hand, lumbar BMD values showed no significant change and only one subject with a
      previous vertebral fracture had one newly occurring vertebral fracture. These
      results indicate that menatetrenone treatment of postmenopausal women constantly
      elevates bone formation markers as well as converts Glu-OC to Gla-OC. Thus,
      vitamin K2 treatment may promote bone formation, at least as measured
      biochemically in these subjects.

PMID- 12201223
TI  - The influence of inflammatory cytokines on estrogen production and cell
      proliferation in human breast cancer cells.
AB  - Estrogens play important roles in the development of breast cancer. Inflammatory
      cytokines such as interleukin-6 (IL-6) and interleukin-1 beta (IL-1 beta) exist
      at high concentrations in breast cancer tissue. Although these cytokines are
      thought to exert some effect on cancer growth, their precise mechanism is still
      unclear. In the present study, we investigated the effects of inflammatory
      cytokines on aromatase (Arom) and steroid sulfatase (STS), which are estrogen
      producing enzymes, and cell proliferation using human breast cancer cell lines
      (SK-BR-3, MCF-7). IL-6 and IL-1 beta stimulated the activity of Arom and STS.
      Estrone sulfate (E1-S) had a stimulus effect on cell proliferation of MCF-7.
      Although IL-6 did not show significant effect on cell proliferation, cell
      proliferation was significantly increased when IL-6 and E1-S were simultaneously
      added to the incubation medium. This cell proliferative effect was apparently
      stronger than the addition of E1-S alone. Addition of IL-1 beta in the presence
      of E1-S also significantly enhanced cell proliferation though IL-1 beta alone did
      not show any effect. These results led us to the hypothesis that inflammatory
      cytokines such as IL-6 and IL-1 beta regulate proliferation of breast cancer
      cells through estrogen production by steroid-catalyzing enzymes in the tissue.

PMID- 12201225
TI  - Broken hairs on the scalp. Dermatologic therapies will not treat this cause of
      solitary hair loss.

PMID- 12201224
TI  - Acid-labile subunit in growth hormone excess and deficiency in adults: evaluation
      of its diagnostic value in comparison with insulin-like growth factor (IGF)-I and
      IGF-binding protein-3.
AB  - In serum, insulin-like growth factors (IGFs) are primarily present as a
      approximately 150 kDa ternary protein complex, which consists of IGFs, IGF
      binding protein-3 (IGFBP-3), and acid-labile subunit (ALS). Like IGF-I and IGFBP
      3, serum levels of ALS depend on growth hormone (GH). To date, the diagnostic
      relevance of ALS in adult GH deficiency (GHD) has remained uncertain. To clarify
      the clinical utility of ALS measurement in adults, we measured serum ALS levels
      in patients with adult GHD or acromegaly. We also measured the levels of serum
      IGF-I and IGFBP-3 in these patients to compare the utility of ALS with IGF-I and
      IGFBP-3 as a marker of GH secretion. Serum ALS was measured by radioimmunoassay
      (RIA) kit, and serum IGF-I and IGFBP-3 were measured by immunoradiometric assay
      (IRMA) kits in 56 patients with adult GHD (adult-onset (AO)/child-onset (CO),
      13/43) and 43 patients with acromegaly. Serum ALS levels were less than 5th
      percentile in 40 of 56 (71%) patients with adult GHD (32/43 (74%) for CO and 8/13
      (62%) for AO), and more than 95th percentile in 38 of 43 (88%) patients with
      acromegaly, respectively. Serum IGF-I levels were less than -1.96 SD in 43 of 56
      (77%) patients with adult GHD (35/43 (81%) for CO and 8/13 (62%) for AO) and more
      than +1.96 SD in 42 of 43 (98%) patients with acromegaly, respectively. Serum
      IGFBP-3 levels were less than -1.96 SD in 51 of 56 (91%) patients with adult GHD
      (42/43 (98%) for CO and 9/13 (69%) for AO) and more than +1.96 SD in 31 of 43
      (72%) patients with acromegaly, respectively. These data suggested that
      measurement of ALS offers no advantage over measurements of serum IGF-I and IGFBP
      3. Furthermore, our results indicate that serum IGFBP-3 is the most suitable
      marker of GH secretion for adult GHD, especially CO, while IGF-I may be the most
      useful in acromegaly.

PMID- 12201226
TI  - Hormone replacement therapy. An analysis of efficacy based on evidence.
AB  - Hormone replacement therapy (HRT) has long been a staple of management of the
      postmenopausal life phase. Over time, and after estrogen therapy was modified to
      include progestin, an increasing number of observational reports suggested that
      HRT conferred benefits well beyond those of managing or minimizing not flashes,
      mood swings, and vaginal dryness. In short, HRT was believed to improve women's
      health and even extend life. One of the most significant theorized benefits was
      protection against cardio- and cerebrovascular events. Other benefits--protection
      against osteoporosis, reduction in incontinence symptoms, and improved cognition-
      have also been linked with HRT. The validity of these theories depended largely
      on observational studies and anecdotal reports, and only lightly (or not at all)
      on randomized clinical trial data. Nevertheless, significant clinical data
      refuting HRT's proposed benefits has been available for several years. Findings
      from these investigations, including new results from two very large trials, show
      that beyond managing traditional menopause symptoms, HRT has little or no role in
      protection against certain diseases or conditions associated with aging. Indeed,
      long-term use of HRT may be contraindicated in most older women with intact
      uteruses.

PMID- 12201228
TI  - Hormone replacement therapy. The sudden halt of a clinical trial shakes long held
      beliefs.

PMID- 12201227
TI  - Anxiety disorders. Helping patients regain stability and calm.
AB  - Anxiety disorders affect more than 19 million American adults and are prevalent
      in the geriatric population. Generalized anxiety disorder, panic disorder, and
      other anxiety types can affect quality of life, precipitate social withdrawal,
      interfere with self-care, and exacerbate health problems. Anxiety disorders also
      may be associated with physical or mental disorders such as heart disease and
      depression. Patients may volunteer information about some anxiety disorders and
      be guarded about others. A proactive patient work-up can help reveal anxiety
      disorders in the primary care setting. Effective symptom management involves a
      combination of psychotherapy (cognitive behavioral) and pharmacotherapy.

PMID- 12201229
TI  - [Parkinson syndrome and cognitive disorders].
AB  - The cognitive (executive) ability of patients with Parkinson's-disease (PD)
      deteriorates gradually during the progression of the disease. Fluency of speech,
      word finding, working memory, ability to plan the future and flexibility decline.
      Cognitive disturbance was found to be proportional with the speech, posture, gait
      and balance problems and can not be influenced by L-dopa substitution. Apart the
      dorsal and ventral mesolimbic dopaminergic systems the coerulo-cortical
      noradrenergic, serotoninergic and cholinergic systems are also impaired in PD.
      Subcortical dementia in PD can also be explained by the functional disability of
      dorsolateral and anterior cingular circuits. Attention deficit can be explained
      by the dopamine depletion of cingular cortex. Cortical Lewy bodies,
      neurofibrillary tangles, neurit plaques and additional vascular pathology should
      also play a role in cognitive impairment of PD. In several systemic degenerative
      diseases associating with Parkinson's syndrome (PS) i.e. progressive supranuclear
      palsy (PSP), corticobasal degeneration (CBD), multiple system atrophy (MSA)
      dementia can be detected with various severity, therefore the question arises
      concerning the correlation between cognitive disability and PS. Parkinson
      syndrome can also develop in frontotemporal dementias (FTD), Alzheimer's disease
      and cortical Lewy body disease (CLBD) but no correlation exists between motor
      disability and severity of dementia. In CLBD dementia can be the initial symptom
      in 18% of cases but PS can also preceeds the dementia. In PSP profound depletion
      of other monoaminergic neurotransmitter system was also reported. In FTDs
      associated with PS degeneration of substantia nigra, locus coeruleus and basal
      nucleus of Meynert has been reported with increased number of neurofibrillary
      tangles. In patients with vascular PS (VP) there is generally no tremor and
      rigidity, but pseudobulbar palsy, dementia, gate disturbance, incontinency
      appears; L-dopa treatment is generally ineffective. In VP no cellular loss can be
      found within the substantia nigra, but leukoaraiosis, lacunae in the white matter
      and basal ganglia are commonly demonstrated.

PMID- 12201230
TI  - [Investigation of the dopamine dysregulation hypothesis of schizophrenia with
      neuroimaging techniques].
AB  - The most elaborated biochemical concept of schizophrenia is the dopamine
      hypothesis. However, this classical theory is based on indirect observations. It
      has recently become possible to study this theory directly by means of advanced
      functional neuroimaging techniques, the development of specific radioligands and
      study protocols that are eligible to monitor dynamic changes in the
      neurotransmitter systems. According to the early concept, the essence of
      schizophrenia is the hyperactivity of the dopamine system. Nevertheless, this
      idea has gone through many modifications. In accordance with the modified
      dopamine hypothesis, the cognitive deficit and negative symptoms are related to
      the hypoactivity of the dorsolateral prefrontal cortex while the acute phases of
      the disease associates with hyperactivity of the ventral striatal elements of the
      dopaminergic system. Between these dysfunctions there is causality via their
      exuberant connections. Beyond that, the interactions between the prefrontal and
      striatal anomalies implicate the involvement of other neurotransmitters than
      dopamine. Observations from model psychosis induced by N-methyl-D-aspartate
      antagonists and in vivo neuroimaging investigations in humans support primarily
      the role of glutamatergic system. Our developing knowledge about the
      neurochemical mechanism of schizophrenia can significantly affect therapeutic
      strategies as well.

PMID- 12201231
TI  - [Cerebellar venous anomalies with symptomatic vascular malformations].
AB  - Cerebral and cerebellar venous anomalies (previously known as venous angiomas)
      form the alternative venous drainage of the surrounding nervous tissue because of
      the un-development of the normal venous system. They are made up of veins with
      abnormal structure: thick walls, lumens dilated and of irregular calibre that
      converge radially towards a wide draining vein (caput medusae). They are thought
      to be a benign condition although they are sometimes associated with cerebellar
      hemorrhages. Authors report three patients with cerebellar venous anomalies
      associated either with pontine cavernoma, cerebellar arteriovenous malformation
      or cerebellar infarct. They illustrate that cerebellar venous anomalies are
      benign conditions, but their presence might be a marker for additional,
      pathogenic malformation. It might be difficult to detect the associated
      malformations even by sophisticated imaging methods, but their presence can
      modify the treatment options.

PMID- 12201232
TI  - [Vertebroplasty: a percutaneous procedure for the treatment of diseased vertebral
      bodies of various etiologies].
AB  - Percutaneous vertebroplasty is a radiologically guided invasive technique
      consisting of the injection of surgical cement into the diseased vertebral body.
      The procedure results in immediate pain relief and strengthening of the bone due
      to the polymerization process of the filling material hardening the vertebral
      body and preventing further collapse. This method is suitable for the treatment
      of osteoporotic vertebral fractures and of osteolytic vertebral body metastases
      without neurological signs, in multiple appearance as well. Authors present
      technical details of the procedure performed by bi-directional fluoroscopy and
      combined CT-fluoroscopy control as well as short-term experience obtained by
      treatment of 17 patients.

PMID- 12201233
TI  - [Molecular genetic background of developmental bony malformations at the
      craniocervical junction and cervical spine].
AB  - In this review a new interpretation of the origin of bony developmental
      malformations affecting the craniocervical junction and the cervical spine is
      presented based on recent advances in the understanding of embryonic development
      of the spine and its molecular genetic control. Radiographs, CT and MRI scans or
      CT myelograms of patients with Klippel-Feil syndrome were used for demonstration.
      Detailed clinical and radiological analysis of these patients was published
      earlier [David KM, Stevens JM, Thorogood P, Crockard HA. The dysmorphic cervical
      spine in Klippel-Feil syndrome: interpretations from developmental biology.
      Neurosurg Focus 1999;6(6):1.]. Homeotic transformation due to mutations or
      disturbed expression of Hox genes is a possible mechanism responsible for Cl
      assimilation. Notochordal defects and/or signalling problems, that result in
      reduced or impaired Pax-1 gene expression, may underlie vertebral fusions. This,
      together with asymmetrical distribution of paraxial mesoderm cells and a possible
      lack of communication across the embryonic mid-line, could cause the asymmetrical
      fusion patterns. The wide and flattened shape of the fused vertebral bodies,
      their resemblance to the embryonic cartilaginous vertebrae and the process of
      progressive bony fusion with age suggest that the fusions occur before or, at the
      latest, during chondrification of vertebrae. The authors suggest that the
      aforementioned mechanisms are likely to be, at least in part, responsible for the
      origin of the bony developmental malformations affecting the craniocervical
      junction and the cervical spine.

PMID- 12201234
TI  - [Neuropsychologic outcome after bilateral pallidotomy in patients with Parkinson
      disease].
AB  - INTRODUCTION: Although significant improvement of motor function following
      bilateral pallidotomy for the treatment of Parkinson's disease has been proved,
      the cognitive sequelae have not been clearly defined. There are recurrent loops
      interconnecting specific areas of the frontal cortex and the basal ganglia,
      suggesting the continuity or complementary functioning between these areas.
      PATIENTS AND METHODS: Pre- and postoperative cognitive function was evaluated in
      19 Parkinsonian patients who underwent bilateral pallidotomy in order to clarify
      its effects on cognitive function. All patients were evaluated one day before the
      procedure and 12+ months after surgery using neuropsychological tests (Raven
      Progressive Matrices and Bergen Facial Recognition Test). Proper performance in
      these tests requires reasoning, abstraction and spatial memory, involving
      strongly the frontal functions. These functions could be described in terms of
      the "working memory" concept. Hand Mental Rotation Test was used as comparing
      task not involving frontal functions. Scores were analyzed by Student's t-test.
      RESULTS: Modest improvement was observed in these cognitive functions as assessed
      by Raven Progressive Matrices (p < 0.0688) and a significant change in the
      complex parts of Bergen Facial Recognition Test (p < 0.0547; p < 0.0468) was also
      noticed, but no change was registered in mental rotation tasks. CONCLUSION:
      Present data revealed that bilateral pallidotomy is associated with modest and
      long-lasting improvement in tasks involving the "working memory".

PMID- 12201235
TI  - [Use of kinematic parameters for assessing motor impairment due to central motor
      neuron damage].
AB  - Evidence based medicine requires objective methods for the assessment of status
      of the patients. The method described by the authors makes it possible to assess
      motoric impairment of patients in an objective way. It is based on three
      dimensional motion analysis. Authors present the case history of two patients
      with spastic hemiparesis due to central nervous system damage. Changes in motoric
      impairment were followed by three-dimensional motion analysis. This method can be
      adapted for the assessment of motor impairment arising from other reasons as
      well.

PMID- 12201236
TI  - [The evolution of psychoneuroimmunology].

PMID- 12201237
TI  - [Karl Emmanuel Jansson: At the door of sacristy 1874].

PMID- 12201238
TI  - [Hannele Kumpulainen: The traditional one].

PMID- 12201239
TI  - [Thrombosis: how to cure the primary cause of death. Symposium proceedings.
      Milano, Italy, 28-29 June 2001].

PMID- 12201240
TI  - Proceedings of the International Conference on Risk Control and Quality
      Management in Neurosurgery. Munich, Germany, October 15-18, 2000.

PMID- 12201241
TI  - Proceedings of the Joint Congress on APL and Differentiation Therapy. October 4
      7, 2001, Rome, Italy.

PMID- 12201242
TI  - Old and New Occupational Exposures and the Lung. Abstracts of the British
      Association for Lung Research Symposium. Leuven, Belgium, September 6-8, 2001.

PMID- 12201243
TI  - Abstracts of the Association of British Neurologists, University of Oxford, 3
      April-5 April 2002.

PMID- 12201244
TI  - [22nd Annual Meeting of the German Society of Senography. Nuremberg, Germany, 6-8
      June 2002. Abstracts].

PMID- 12201245
TI  - High-dose intravenous 'pulse' methylprednisone in the treatment of severe
      oropharyngeal pemphigus: a pilot study.
AB  - BACKGROUND: High-dose intravenous (i.v.) methylprednisolone has been used
      therapeutically in severe blistering diseases to avoid the complications and side
      effects of long-term orally administered glucocorticoid therapy. The aim of the
      study is to evaluate the capacity of methylprednisolone i.v. 'pulse' therapy to
      induce remission in the treatment of severe oropharyngeal pemphigus. METHODS:
      Twelve patients, all of whom had oropharyngeal severe pemphigus, were included in
      the analysis. There were eight women and four men whose ages ranged from 22 to 78
      years (mean age: 50.75 years) with a disease duration of 1-3 months(mean
      duration: 55 days). In order to obtain a rapid clinical remission of extensive
      mucosal lesions, we performed 'pulse' therapy with intravenous methylprednisolone
      (30 mg/kg body weight to a maximum of 1 g per dose on each of 3-5 consecutive
      days)evaluating the clinical response and the short-term side-effects. RESULTS:
      Our therapy was generally safe and well tolerated with a very low rate of side
      effects. All patients responded to i.v. methyl-prednisolone with evidence of a
      decrease in signs and symptoms within l week of commencing treatment and in all
      cases remission was observed after the second or the third cycle of 'pulse'. The
      most common adverse events during treatment were flushing and hyperglycaemia; in
      a few cases we observed a metallic taste in the mouth, pruritus, headaches
      ranging from mild to moderate, palpitations, mood alterations, insomnia and
      fatigue. CONCLUSIONS: High-dose 'pulse' administration of glucocorticoids is a
      potentially effective therapy to be considered in the treatment of patients with
      severe oropharyngeal pemphigus. Similar patients treated with conventional oral
      administered doses of prednisone or deflazacort had protracted courses requiring
      months of glucocorticoid therapy with no long-term remissions. However, further
      well-designed, long-term comparative trials are required to confirm this.

PMID- 12201246
TI  - SPARC stimulates the synthesis of OPG/OCIF, MMP-2 and DNA in human periodontal
      ligament cells.
AB  - BACKGROUND: Osteonectin/secreted protein, acidic and rich in cysteine (SPARC) is
      expressed in periodontal ligaments. Therefore, a better understanding of the
      action of SPARC on periodontal ligament cells could help to elucidate remodelling
      and repair mechanisms in periodontal tissue. In the present study, we examined
      the effects of human platelet-derived SPARC (hp-SPARC) on the expressions of
      SPARC and osteoprotegerin/osteoclastogenesis inhibitory factor (OPG/OCIF),
      alkaline phosphatase (ALPase) activity, matrix metalloproteinase-2 (MMP-2)
      production and DNA synthesis in cultures of human periodontal ligament (HPL)
      cells. METHODS: HPL cells at the sixth passage were exposed to hp-SPARC. The
      expression of OPG/OCIF and SPARC mRNAs was examined by Northern blot analysis.
      The protein levels for OPG/OCIF and MMP-2 were determined by Western blot
      analysis. ALPase activity was measured by the method of Bessey et al. DNA
      synthesis was estimated by incorporation of [3H] thymidine. RESULTS: Hp-SPARC
      enhanced OPG/OCIF synthesis at the protein and mRNA levels. Hp-SPARC also
      enhanced DNA and MMP-2 synthesis dose-dependently, but had little effect on
      ALPase activity and SPARC mRNA expression. CONCLUSION: SPARC may play a role in
      remodelling and repair of periodontal tissue by promoting proliferation and MMP-2
      production. It may also regulate osteoclast formation through OPG/OCIF in
      periodontal ligament cells.

PMID- 12201247
TI  - Disturbed tooth eruption in osteopetrotic (op/op) mice: histopathogenesis of
      tooth malformation and odontomas.
AB  - BACKGROUND: Odontoma-like structures are formed in the jaw bone of osteopetrotic
      (op/op) mice, which have a congenital deficiency in osteoclastic differentiation
      due to the absence of functional macrophage colony-stimulating factor (M-CSF).
      METHODS: To clarify the histopathogenesis of tooth malformation and odontoma-like
      structures, a 2-year postnatal process of development of the op/op mandibular
      incisor was examined radiologically and histologically. At the same time,
      extracellular matrix (ECM) remodeling around tooth germs was analyzed
      immunohistochemically. RESULTS: Abnormal forms of op/op tooth germ were
      noticeable even at 3 days after birth on a radiogram. Histologically, op/op mice
      were clearly distinguished by the disappearance of dental follicular space at 3
      days. With aging, bone trabeculae, which were not remodeled, penetrated into
      op/op tooth germs and divided them into several daughter germs, which were
      recognized as odontomas. In mandibular incisor bodies, the immature ECM
      components, such as heparan sulfate proteoglycan and tenascin, were preserved
      diffusely in the dental papilla/pulp, which indicates that maturation of the
      stroma does not take place in op/op mandibular incisors. CONCLUSION: The
      observation suggests that the disturbed morphogenesis of op/op tooth germs is
      functionally explained by the disordered immunolocalization of ECM molecules, and
      that the dental follicular space is essential for normal tooth development
      because it prevents bone penetration into the tooth germs.

PMID- 12201248
TI  - No developmental failure of cultured tooth germs from osteopetrotic (op/op) mice.
AB  - BACKGROUND: Incisor tooth germs of osteopetrotic (op/op) mice are known to fail
      to erupt, but form odontomas in their root apices instead, due to invasion of
      alveolar bone trabeculae into the tooth germs. The purpose of this study is to
      determine if the tooth developmental failures in op/op mice are intrinsic or
      secondarily arise as a result of the defective bone metabolism due to lack of
      macrophage colony-stimulating factor (M-CSF). METHODS: We isolated mandibular
      first molar tooth germs from normal and op/op mice and cultured them under
      conditions with or without bone tissues which had been formed around tooth germs.
      RESULTS: Tooth germs from normal mice, cultured for a week, showed almost the
      same developmental features as those of mice with the corresponding age. They
      were surrounded with dental follicular tissues and were never invaded by bone
      trabeculae. On the other hand, op/op tooth germs cultured in the presence of bone
      components were invaded by alveolar bone trabeculae around tooth germs in the
      same manner as shown in vivo. When cultured without bone, they developed without
      any interruptions. CONCLUSIONS: These findings indicated that op/op tooth germs
      had potential for normal development and that their abnormal development was a
      secondary phenomenon caused by lack of bone remodeling in the early phase of
      odontogenesis.

PMID- 12201249
TI  - Performance improvement initiative reduces use of restraints.

PMID- 12201251
TI  - Orthopedic proceedings 2000, 2001.

PMID- 12201250
TI  - [Abstracts of the 56th Congress of The Hungarian Surgical Society. Budapest, June
      12-14, 2002].

PMID- 12201252
TI  - Abstracts of the American Academy of Otolaryngology--Head and Neck Surgery
      Foundation, Inc. San Diego, California, USA. September 22-25, 2002.

PMID- 12201253
TI  - Abstracts of the (ASSA-SAGES) Association of Surgeons of South Africa and South
      African Gastroenterology Society 2002 Congress. Sun City, 14-19 June 2002.

PMID- 12201254
TI  - Abstracts of the 28th Annual Meeting of the European Thyroid Association.
      Goteborg, Sweden, September 7-11, 2002.

PMID- 12201255
TI  - Symposium Mammographicum 2002. University of York, 17-19 July 2002. Abstracts.

PMID- 12201256
TI  - British Geriatrics Society Spring Meeting Abstracts. 11-12 April 2002, Telford.

PMID- 12201257
TI  - Abstracts and educational programme of the 24th Congress of the European Society
      of Parenteral and Enteral Nutrition. Glasgow, United Kingdom, 31 August-4
      September 2002.

PMID- 12201258
TI  - Sustainable use of anthelmintics in grazing animals.
AB  - It is suggested that the major factor in avoiding the development of anthelmintic
      resistance is the percentage of worms that do not encounter the anthelmintics
      (worms in refugia). This in turn is determined by the numbers of larvae on
      pasture, the percentage of animals treated and whether any stages in the host can
      avoid the action of anthelmintic. To maintain anthelmintic efficacy the
      percentage of worms in refugia must be sufficiently large. In cattle, this should
      involve treating only first-year animals and using a different pasture each year
      for calves. For sheep, only animals that have to be treated should be dosed with
      anthelmintic and clean grazing strategies that involve the use of anthelmintics
      should be avoided. For horses, reliance should be placed on the removal of faeces
      from pasture and only treating when the animals' condition requires it. Without a
      change in anthelmintic use there is the likelihood of increasing numbers of cases
      for which no anthelmintic is effective and animal welfare may be compromised.

PMID- 12201259
TI  - Study of clinical mastitis in British dairy herds with bulk milk somatic cell
      counts less than 150,000 cells/ml.
AB  - A 12-month prospective study of clinical mastitis was conducted in 482 British
      dairy herds with a bulk milk somatic cell count (BMSCC) of less than 150,000
      cells/ml. The mean proportion of cows in the herd with clinical mastitis was 23.1
      per cent (range 0 to 80), with a mean of 1.50 quarter cases per cow. The mean
      incidence rate of clinical mastitis was 36.7 quarter cases per 100 cow years
      (range 0 to 208.2). Twelve per cent of the quarter cases showed systemic signs,
      including inappetence and severe lethargy. Over 22 per cent of quarter cases
      occurred in the first seven days of lactation and over 50 per cent occurred in
      the first 90 days of lactation. Cluster analysis indicated that the main
      difference between herds with a low and average incidence of mastitis was the
      proportion of clinical cases occurring in the first seven days of lactation, 14
      per cent compared with 44 per cent, respectively. The risk of severe clinical
      mastitis compared with mild clinical mastitis decreased significantly as the
      individual cow somatic cell count (SCC) in the month before clinical mastitis was
      diagnosed increased.

PMID- 12201260
TI  - Ocular onchocercosis in dogs: a review.
AB  - In recent decades, sporadic cases of ocular Onchocerca species infection have
      been reported in dogs in the USA and Europe. In the acute stage of the disease
      severe inflammation of the ocular and periocular tissues was observed. In chronic
      cases, the strongly coiled, gravid nematodes were incorporated in pea- to bean
      sized granulomatous nodules in various parts of the eye, including the
      retrobulbar space, orbital fascia, eyelid, third palpebra, conjunctiva and
      sclera. Apart from the ophthalmological significance of the disease, the large
      number of microfilariae in the skin may be responsible for acute and chronic
      dermatological problems. The geographical distribution and prevalence of the
      infection may be greater than currently thought, because the lesions may have
      been erroneously regarded as other ocular diseases. Onchocerciasis is the world's
      second most prevalent infectious cause of blindness in human beings and
      parasitologists have long searched for an experimental model of human
      onchocerciasis; ocular onchocercosis infections in dogs may provide a useful
      experimental system.

PMID- 12201261
TI  - Potency and postantibiotic effect of four fluoroquinolones against feline
      Pasteurella multocida isolates.

PMID- 12201262
TI  - Ulcerative glossitis in a dog with leishmaniasis.

PMID- 12201263
TI  - Subluxation of the left elbow joint in a pony at induction of general
      anaesthesia.

PMID- 12201264
TI  - Out-of-hours working.

PMID- 12201265
TI  - RCVS disciplinary hearing.

PMID- 12201266
TI  - Serological survey for sleeping disease in trout in Northern Ireland.

PMID- 12201267
TI  - RCVS fees for 2003.

PMID- 12201268
TI  - Transmission of psittacine haemoproteids.

PMID- 12201269
TI  - Avian influenza in poultry in Chile.

PMID- 12201270
TI  - Withdrawal times for medicines on organic farms.

PMID- 12201273
TI  - From the Centers for Disease Control and Prevention. Heat-related deaths--four
      states, July-August 2001, and United States, 1979-1999.

PMID- 12201274
TI  - From the Centers for Disease Control and Prevention. Outbreak of multi-drug
      resistant Salmonella Newport--United States, January-April 2002.

PMID- 12201275
TI  - From the Centers for Disease Control and Prevention. Resumption of routine
      schedule for diphtheria and tetanus toxoids and acellular pertussis vaccine and
      for measles, mumps, and rubella vaccine.

PMID- 12201276
TI  - From the Centers for Disease Control and Prevention. Resumption of routine
      schedule for varicella vaccine.

PMID- 12201277
TI  - Abstracts of the 11th Congress of the Association of European Psychiatrists.
      Stockholm, Sweden, 4-8 May 2002.

PMID- 12201278
TI  - New rules announced on confidentiality of US patient records.

PMID- 12201279
TI  - Preventing stroke with ramipril. Benefits were considerably overstated.

PMID- 12201280
TI  - Preventing stroke with ramipril. Superiority of particular class of
      antihypertensive agent remains to be shown.

PMID- 12201281
TI  - Preventing stroke with ramipril. Presentation of data is misleading.

PMID- 12201283
TI  - Burden of illness and suicide in elderly people. Death, where's thy sting?

PMID- 12201284
TI  - Increasing response rates to postal questionnaires. Effect of incentives on
      response rates must be considered.

PMID- 12201286
TI  - Society for the Study of Inborn Errors of Metabolism 40th Annual Symposium.
      Dublin, Republic of Ireland, 3-6 September 2002. Abstracts.

PMID- 12201285
TI  - [The Brazilian Society of Cardiology Guideline for Nuclear Cardiology].

PMID- 12201287
TI  - Abstracts of the 33rd Annual Meeting of the the American Society for
      Neurochemistry. Palm Beach, California, USA. June 22-26, 2002.

PMID- 12201288
TI  - New guidelines for measuring health status.

PMID- 12201289
TI  - Census Bureau releases data on people who chose more than one race.

PMID- 12201291
TI  - How young people use the Internet for health information.

PMID- 12201290
TI  - Syphilis rates decline.

PMID- 12201292
TI  - Impact of Endocrine Disruptors on Brain Development and Behaviour. Proceedings of
      a conference. 15-20 September 2001, Sicily, Italy.

PMID- 12201293
TI  - An individual's privacy versus the rights of society.

PMID- 12201294
TI  - Lactic acidosis and anti-retroviral drugs.
AB  - (1) Lactic acidosis is a serious, often fatal adverse reaction to nucleoside HIV
      reverse transcriptase inhibitors. (2) The presenting symptoms are non specific,
      and include gastrointestinal upset, fatigue, fever, and breathlessness. They
      appear gradually after several weeks or months of antiretroviral treatment. (3)
      Moderate hyperlactataemia, with few if any symptoms, is common in patients taking
      nucleoside inhibitors, and is not predictive of severe lactic acidosis. (4) Cases
      of lactic acidosis were reported in newborns whose mothers were given nucleoside
      inhibitors to reduce the risk of mother to child transmission of HIV. (5) In
      practice, hyperlactataemia should be suspected in patients taking antiretroviral
      drugs who present with unexplained symptoms, and especially breathlessness.
      Elevated lactataemia (especially above 5 mmol/l) requires rapid withdrawal of
      antiretroviral treatment.

PMID- 12201295
TI  - Human cloning: brave new mistake.

PMID- 12201296
TI  - Human cloning? No thanks.

PMID- 12201297
TI  - Physician cooperation in patient suicide.

PMID- 12201299
TI  - Reflections on the status of brain death.

PMID- 12201298
TI  - A medical defense of brain death.

PMID- 12201300
TI  - A case of comatose pregnancy.

PMID- 12201301
TI  - Teaching Catholic bioethics.

PMID- 12201302
TI  - Destroying human embryos for research.

PMID- 12201303
TI  - A non-heart-beating donor protocol.

PMID- 12201304
TI  - Removing ventilatory life support.

PMID- 12201305
TI  - Responses to smallpox vaccine.

PMID- 12201306
TI  - Volume and outcome.

PMID- 12201307
TI  - Volume and outcome.

PMID- 12201308
TI  - Volume and outcome.

PMID- 12201309
TI  - Volume and outcome.

PMID- 12201310
TI  - Volume and outcome.

PMID- 12201311
TI  - Volume and outcome.

PMID- 12201312
TI  - Volume and outcome.

PMID- 12201313
TI  - Alleged violations of subject protection rules led to an indefinite research
      shutdown.

PMID- 12201314
TI  - Invalidated state regulations violated subjects' rights.

PMID- 12201316
TI  - From the president of EACME.

PMID- 12201315
TI  - Spotlight on oral health.

PMID- 12201317
TI  - Clinical trials and legal jeopardy.
AB  - On neither side of the Atlantic have research ethics committees found a
      satisfactory way of ensuring that all serious side-effects of new treatments
      being studied are noted and reported to them, without being deluged in reports of
      minor adverse events. The author of the following paper is probably the leading
      historian of psychopharmacology: he discusses the issue, and its implications for
      RECs, in the light of the serious side-effects of the new generation of SSR
      antidepressants.

PMID- 12201318
TI  - Medical treatment (prevention of euthanasia).

PMID- 12201319
TI  - Gene Therapy Advisory Committee.

PMID- 12201320
TI  - Health promotion and human rights.

PMID- 12201321
TI  - Oral contraceptives: views among primary health-care physicians and the general
      population.
AB  - OBJECTIVES: To ascertain the views of physicians and the general population
      concerning oral contraceptive (OC) use and the risk of thrombosis after the pill
      scare and, moreover, to investigate whether respondents' smoking habits had any
      impact on these perceptions. METHOD: A questionnaire on family planning was
      mailed to randomly selected Finnish health-center physicians (n = 351) and to a
      random sample of Finnish women (n = 393) and men (n = 395). All were asked to
      evaluate statements concerning OCs using a visual analog scale from 0 (strongly
      disagree) to 100 (strongly agree). RESULTS: The response rate for physicians was
      69%, for women 56% and for men 45%. Respondents in all subgroups agreed to some
      extent that OCs increase the risk of thrombosis. Among the population, more women
      than men were of the opinion that it is dangerous to smoke while using OCs and
      non-smokers were more aware of the risk of OC use and simultaneous smoking than
      were smokers. Physicians' personal smoking habits had no evident impact on
      opinions concerning OC use, risk of thrombosis and smoking. CONCLUSIONS: Although
      differences existed between the perceptions of physicians and those of the
      general population concerning OCs, their opinions are realistic and in harmony.

PMID- 12201322
TI  - Evaluation of a mass media campaign on contraception in France.
AB  - OBJECTIVE: Three short films, promoting a national contraception campaign, were
      broadcast on French television in January 2000. As media interventions alone have
      little impact on behavior, we evaluated this campaign by focusing on intermediary
      indicators (identification and discussion) to measure factors known to favor the
      adoption of preventive behaviors. METHODS: A representative sample of 342 women,
      aged between 15 and 55 years, was selected for interview 2 months after the
      campaign. An additional sample of 254 young women (aged 15-25 years) was included
      to improve our understanding of the opinions and practices of this age group.
      RESULTS: The campaign attracted much public attention and was well accepted.
      However, only 44% of the women found that they could identify with the situations
      presented. The films did not generate much conversation, with only one in four
      people reporting having talked about them. Women who had reported problems with
      contraception were no more likely to identify with the situations presented in
      the films or to discuss them with others than those who had no contraceptive
      problems. The factors associated with these processes (perceptions of the films,
      having a confident, past unintended pregnancy) differed according to age group.
      CONCLUSION: Although this campaign was well received, it had a limited impact.
      Moreover, it did not have a greater impact on people who experienced difficulties
      with their contraception. The short projection time and the scenarios used (which
      gave an immediate answer to women's questions) might have limited these effects.

PMID- 12201323
TI  - Coitus-dependent and coitus-independent contraceptive methods in women and men.
AB  - OBJECTIVE: To study the use of contraceptives in Sweden. METHODS: Analysis of the
      population-based survey 'Sex in Sweden. On the Swedish sexual life 1996'. The
      survey was analyzed in relation to socio-demographic, lifestyle, sexual and
      behavioral characteristics as well as attitudes to, and evaluation of, personal
      experiences. The data included 2810 men and women between 18 and 74 years of age.
      The results were compared with a similar survey carried out in 1967. RESULTS:
      During the 30-year period between the 1967 and 1996 surveys, condom use more than
      halved and use of oral contraceptives increased by 6 percentage points. The
      decline in the use of condoms did not occur among teenagers but among all other
      age groups in both men and women. In 1996 the majority (72%) used a reliable
      contraceptive method, but 29% did not. Coitus-dependent methods were more
      frequently used by men and women who were below the age of 21, smoked, used
      alcohol simultaneously with coitus, had casual partners, were more highly
      educated, were breastfeeding, had coitus less frequently and among those who were
      most satisfied with their sexual life and their partner relationship. CONCLUSION:
      In order to increase the use of more reliable contraceptive methods, three
      crucial factors should be focused on in counselling and media campaigns: gender,
      age and the use of coitus-dependent/coitus-independent methods.

PMID- 12201324
TI  - Outcomes at 1 year for the first 200 patients fitted with GyneFix at Margaret
      Pyke Centre.
AB  - The first 200 women to be fitted with GyneFix at the Margaret Pyke Centre, a
      National Health Service contraception clinic situated in central London, have
      been followed up at 1 year after insertion. Removals, expulsions and accidental
      pregnancies in that first year are recorded. Of the cohort, 80% had a known
      outcome at 12 months. There was one perforation with the inserter tube, leaving
      199 women fitted with GyneFix who contributed 2033 woman-months of follow-up
      time. We recorded 22 early removals, of which 16 were for heavy or irregular
      bleeding and/or pain, three were because the women wished to conceive and three
      for other reasons. In addition there were 16 expulsions at intervals ranging from
      1 day to 12 months after insertion. Four of the expulsions were unnoticed by the
      subjects (they were revealed by amenorrhea of pregnancy in two subjects and lost
      threads in the other two). There were no pregnancies with the GyneFix in situ.
      The expulsion rate of 8.4% (confidence interval (CI) 5.2-13.4%) and removal rate
      for bleeding and/or pain of 9.0% (CI 5.6-14.3%) at 12 months recorded in this
      cohort fall within acceptable ranges for framed intrauterine devices in a
      population with a large percentage of nulliparous women. However, they are
      perhaps not as good as had been anticipated for this revolutionary new
      intrauterine implant. Possible reasons for this are explored.

PMID- 12201325
TI  - Pilot study of short-term acceptability and breakage and slippage rates for the
      loose-fitting polyurethane male condom eZ.on bi-directional: a randomized cross
      over trial.
AB  - OBJECTIVE: To assess the short-term acceptability and functionality of the eZ.on
      condom compared with currently marketed latex (Gossamer) and polyurethane
      (Avanti) condoms. Method Healthy, sexually active volunteers aged 18-50 years,
      self-selected from among the UK population, were enrolled in a randomized cross
      over trial. Participants were required to test six of each of three condom
      variants. Data were collected on structured questionnaires by means of postal and
      telephone contacts. Main outcome measures were breakage and slippage rates, and
      short-term user acceptability based on participants' ratings documented in end-of
      study questionnaires. RESULTS: Forty-three couples entered the study, of whom 37
      tested the condoms on 512 occasions. There was no statistically significant
      difference in the clinical breakage rate between eZ.on (3.7%) and the comparator
      condoms (3.5% for Gossamer and 2.9% for Avanti). Complete slippage rates were
      similar for eZ.on (2.4%) and Avanti (2.9%). Gossamer had the lowest slippage rate
      (1.2%), but this difference was not statistically significant. User acceptability
      was similar for the three condom types; however, there was a trend for more
      participants to express dissatisfaction with eZ.on, including difficulties with
      putting on the condom. CONCLUSIONS: No firm conclusions can be drawn from this
      pilot study, but our observations suggest that eZ.on may be an acceptable option
      for some couples unwilling or unable to use a latex condom.

PMID- 12201326
TI  - A pharmacokinetic study with a low-dose oral contraceptive containing 20 microg
      ethinylestradiol plus 100 microg levonorgestrel.
AB  - This study investigated the pharmacokinetics of a dose-reduced oral contraceptive
      containing 20 microg ethinylestradiol (EE) + 100 microg levonorgestrel (LNG) in
      18 young, healthy females. Serum levels of EE and LNG were determined after
      single and repeated daily oral administration over three treatment cycles, each
      consisting of 21 treatment days followed by a 7-day treatment-free period.
      Additionally, the time courses of sex hormone-binding globulin (SHBG), corticoid
      binding globulin (CBG) and total and free testosterone serum levels were
      analyzed. Both active ingredients were rapidly absorbed and maximum
      concentrations in serum were reached between, on average, 1 and 2 h after single
      and multiple administrations, respectively. Concentrations of EE increased during
      repeated daily administration. An approximate two-fold accumulation was
      calculated based on the comparison of EE area under the curve (AUC) (0-24 h)
      values determined after the first and the last tablet administration within a
      treatment cycle. LNG serum concentrations also increased during repeated daily
      administration, reaching steady-state levels after about 11 days. Based on the
      comparison of AUC (0-24 h) values determined after the first and the last tablet
      administration, LNG accumulated approximately by a factor of 3 within a treatment
      cycle. Steady-state pharmacokinetics of LNG were similar at the end of the first
      and the third treatment cycles, indicating no further accumulation of LNG beyond
      a treatment cycle under long-term use of this combined oral contraceptive. The
      clearance and volume of distribution of LNG decreased and the terminal half-life
      increased after repeated daily administration, compared with single
      administration. These effects have also been reported for other LNG/EE
      combinations. SHBG serum concentrations increased during repeated daily intake
      by, on average, 1.5-1.6-fold, and for CBG, an average increase of 1.4-1.8-fold
      was found. Although free testosterone concentrations declined during repeated
      daily administration by about 40%, total testosterone remained relatively
      unchanged at a low level. In conclusion, the pharmacokinetics of EE and LNG
      determined in the present study were in good agreement with those previously
      reported for 30 microg EE + 150 microg LNG, taking the 33% dose reduction into
      account.

PMID- 12201327
TI  - Safety and tolerability of the new contraceptive sponge Protectaid.
AB  - OBJECTIVE: This study was undertaken to assess the efficacy, safety and
      acceptability of two different-dose regimens of the Protectaid contraceptive
      sponge. METHODS: The toxic effects of two forms of the new vaginal contraceptive
      sponge, Protectaid, in the cervical and vaginal tissues were studied. Both types
      were impregnated with F-5 gel containing different doses of nonoxynol-9 (NX9;
      0.5% and 0.125%). The sponge was used by 35 women aged 20-35 years (mean 28.7
      years) randomly allocated into two groups (Group A: 0.5% NX9, n = 20; Group B:
      0.125% NX9, n = 15). RESULTS: During a 12-month period both regimens demonstrated
      a 91.4% overall contraceptive efficacy. Colposcopic examinations showed no
      significant cervical or vaginal lesions in either group, except for two cases at
      the 2-week and 3-month examinations in Group A women. In the former, inflammatory
      changes of little clinical significance were seen and the colposcopic appearance
      of the vagina was non-specific. In this case, the focal lesions were accompanied
      by dilated capillaries (hyperemia). In the second case, degenerative inflammatory
      changes, with the inflammatory foci varying in shape and distribution, were
      observed. Cervical cultures taken 6 months after the start of treatment showed
      the presence of Mycoplasma hominis and Candida albicans in one and two cases,
      respectively, in Group A. In Group B, cervical cultures taken at 3 months showed
      Gardnerella vaginalis and beta-hemolytic streptococci group B in one and two
      cases, respectively. CONCLUSION: The potent spermicidal and protective properties
      of this new contraceptive sponge may be of benefit to the sexually active female.
      Since the sponge was very well accepted by both the study participants and their
      sexual partners, it can be considered as a valuable barrier method.

PMID- 12201328
TI  - Natural contraception using the Billings ovulation method.
AB  - OBJECTIVE: The Billings ovulation method (BOM) is a medical model of a natural
      procreation education method based on scientific observation of the changes in
      the cervical mucus. In this study we examined Turkish women's interest in
      accurate usage of cervical mucus changes in determining the ovulation time.
      METHOD: Fifteen regularly cycling women monitored their fertility patterns in 30
      cycles using the BOM and urine luteinizing hormone (LH) kits. At the end ofeach
      cycle, the cervical mucus monitoring chart and LH kits were collected from the
      subjects and analyzed. RESULTS: The cervical mucus symptoms defined a potential
      fertile period of 10 days' average length, with the 'peak' mucus characteristic
      occurring at a mean of day 13.65 +/- 2.62 of the cycle. The duration ofthe LH
      surge, as observed in early morning urine samples, averaged 5 days, with the peak
      occurring at a mean of day 13.40 +/- 2.58 of the cycle. Data indicated that there
      was a strong correlation between LH in the urine and the peak in self-observed,
      cervical-vaginal mucus (p = 0.001). CONCLUSION: This study proved that women can
      distinguish patterns of ovulation and anovulation by self-detection of variations
      in cervical mucus characteristics, and that urinary LH levels strongly correlate
      with ovulation.

PMID- 12201329
TI  - Age- and sex-related differences in temporal judgments to visual stimuli: support
      for hemispheric equivalence.
AB  - Light-emitting diodes in avisual half-field display were employed to examine
      hemispheric asymmetries in temporal resolution among young and older adults.
      Participants judged whether pairs of spatially separated diodes were illuminated
      simultaneously. No visual field threshold differences emerged for either age
      group, thus supporting hemispheric equivalence. Older adults had significantly
      higher thresholds than did younger adults, regardless of spatial location. The
      results further revealed that older females had significantly higher thresholds
      than did older males, younger males, and younger females. The results further
      revealed sex differences, favoring females, when interhemispheric transfer times
      (IHTTs) were examined for a central bilateral presentation. However, sex effects
      were not revealed when IHTTs were examined for a peripheral bilatepresentation,
      indicating a disadvantage forolder females.

PMID- 12201330
TI  - Perception of timing is more context sensitive than sensorimotor synchronization.
AB  - In three experiments, the effects of contextual temporal variation on the
      perception of timing and on sensorimotor synchronization were examined.
      Experiment 1 showed that exposure to a variably timed auditory precursor sequence
      reduces the detectability of deviations from isochrony in a musical test
      sequence. By contrast, in Experiment 2 there was only a small and transient
      effect of identical precursor sequences on the variability of finger taps that
      were synchronized with a similar test sequence. Moreover, the precursor did not
      impede phase error correction following deviations from isochrony in the test
      sequence. Experiment 3 employed a within-subjects design that required
      simultaneous detection of irregularities in and synchronization with nonmusical
      auditory sequences. Precursor variability impaired only detection, not
      synchronization performance. These results suggest that perception of deviations
      from regularity engages context-sensitive tining processes, probably related to
      conscious awareness, that are not involved in sensorimotor synchronization.

PMID- 12201331
TI  - Contribution of extraretinal signals to the scaling of object distance during
      self-motion.
AB  - We investigated the role of extraretinal information in the perception of
      absolute distance. In a computer-simulated environment, monocular observers
      judged the distance of objects positioned at different locations in depth while
      performing frontoparallel movements of the head. The objects were spheres covered
      with random dots subtending three different visual angles. Observers viewed the
      objects ateye level, either in isolation or superimposed on a ground floor. The
      distance and size of the spheres were covaried to suppress relative size
      information. Hence, the main cues to distance were the motion parallax and the
      extraretinal signals. In three experiments, we found evidence that (1) perceived
      distance is correlated with simulated distance in terms of precision and
      accuracy, (2) the accuracy in the distance estimate is slightly improved by the
      presence of a ground-floor surface, (3) the perceived distance is not altered
      significantly when the visual field size increases, and (4) the absolute distance
      is estimated correctly during self-motion. Conversely, stationary subjects failed
      to report absolute distance when they passively observed a moving object
      producing the same retinal stimulation, unless they could rely on knowledge of
      the three-dimensional movements.

PMID- 12201332
TI  - Two bs or not two Bs? A signal detection theory analysis of repetition blindness
      in a counting task.
AB  - Stimulus repetition usually benefits performance. A notable exception is
      repetition blindness (RB), in which subjects fail to report a repeated stimulus
      in a rapid serial visual presentation. Theories differ in attributing RB to
      either perceptual encoding or memory retrieval and to impaired discrimination
      versus response bias. In the present study, subjects judged whether one or two
      letters were imbedded in sequences of digits. Unlike previous studies, false
      guesses of two unrepeated letters were distinguished from false guesses of two
      repeated letters. When repeated- and unrepeated-letter trials were randomly
      intermixed (Experiment 1), RB was entirely attributable to response bias.
      However, when they were separately blocked (Experiments 2 and 3), RB was
      manifested in discriminability (d'). The results support perceptual-encoding
      accounts of RB but indicate that effects on discriminability depend on subjects'
      processing strategies.

PMID- 12201333
TI  - Made you blink! Contingent attentional capture produces a spatial blink.
AB  - Previous studies have shown that the capture of attention by an irrelevant
      stimulus can be eliminated by fore knowledge of the spatial location of the
      relevant target stimulus. To explore whether spatial certainty is sufficient to
      eliminate capture, four experiments are reported in which the spatial location of
      the target is certain but the temporal position is uncertain. Subjects viewed a
      central rapid serial visual presentation stream in which a target letter was
      defined by a particular color (e.g., red). On critical trials, irrelevant color
      singletons appeared in the periphery. In Experiments 1 and 2, peripheral
      singletons produced a decrement in central target identification that was
      contingent on the match between the singleton color and the target color.
      Experiments 3 and 4 provided evidence that this decrement reflected a shift of
      spatial attention to the location of the distractor. The results suggest that
      spatial certainty is not sufficient to eliminate attentional capture and that
      attentional capture can result in a spatial "blink" that is conditional on top
      down attentional control settings.

PMID- 12201334
TI  - Voluntazy and automatic attentional control of visual working memory.
AB  - Previous studies of attention-directing cues have focused largely on the effects
      of cuing on perceptual processes, but cuing may also influence the transfer of
      perceptual representations into visual working memory. In the present study, we
      examined this potential role of cues, using both predictive and non-predictive
      cues in the context of a visual working memory task. Each trial began with a cue,
      followed by an array of six colored squares, a delay interval, and then a probe
      square presented at th e location of one of the squares in the previous array.
      The subjects were required to indicate whether the color of the probe square was
      the same as the color of the square that had previously been presented at the
      same location. Performance on this working memory task was more accurate when the
      cued location was probed than when an uncued location was probed, even when the
      cued location was no more likely to be probed than any of the uncued locations.
      An additional experiment using the abrupt-onset paradigm of Yantis and Jonides
      (1984) yielded similar results. Thus, visual transients may automatically
      influence the transfer of perceptual representations into visual working memory.

PMID- 12201335
TI  - Irrelevant singletons capture attention: evidence from inhibition of return.
AB  - Previous research has shown that a salient feature singleton may capture
      attention in a stimulus-driven, bottom-up fashion (e.g., Theeuwes, 1992,1994b).
      This conclusion has been challenged by others claiming that the observed
      attentional capture by irrelevant singletons may not be stimulus driven but due
      to top-down attentional control settings and/or nonspatial filtering costs. In
      the present study, we show that inhibition of return (IOR) occurs at the location
      of an irrelevant singleton. Participants were slower to detect a target presented
      at the location of the irrelevant singleton, relative to other locations. Since
      IOR can be observed only as a result of an exogenous, stimulus-driven shift of
      spatial attention, it isun-likely that top-down control settings and/or
      nonspatial filtering costs played a role. In line with earlier claims, the
      present findings provide strong evidence that salient singletons capture spatial
      attention in a purely bottom-up way.

PMID- 12201337
TI  - Does "whole-word shape" play a role in visual word recognition?
AB  - To analyze the impact of outline shape on visual word recognition, the visual
      pattern of the stimuli can be distorted by size alternation. Contrary to the
      predictions of models that rely on outline shape (Allen, Wallace, & Weber, 1995),
      the effect of size alternation was greater for low-frequency words than for high
      frequency words in a lexical decision task (Experiment 1). In Experiment 2, the
      effect of case type (lowercase vs. UPPERCASE) occurred for low-frequency words,
      but not for high-frequency words. The effect of neighborhood size was remarkably
      similar in the two experiments. The results can be readily explained in the
      framework of a resonance model (Grossberg & Stone, 1986), in which a mismatch
      between the original sensory pattern and the abstract orthographic code slows
      down the formation of a stable percept.

PMID- 12201336
TI  - Auditory frequency-based inhibition differs from spatial IOR.
AB  - Uninformative auditory frequency cues have a facilitatory effect on reaction time
      and accuracy of detection and intensity discrimination of target tones for cue
      target intervals of up to 3 sec (Green & McKeown, 2001; Ward, 1997). Under some
      conditions, however, this facilitatory effect can reverse to an inhibitory effect
      at cue-target intervals longer than 450 msec (Mondor, Breau, & Milliken, 1998).
      Thepresent work demonstrates that such inhibitory effects are not found in target
      target experiments (Experiment 1) or in cue-target experiments requiring a go-no
      go discrimination of the target (Experiment 2), whereas they do appear in the
      paradigm used by Mondor et al. (1998, Experiment 3), albeit unaffected by the
      similarity of cue and target. Thus, the frequency-based inhibitory effects
      sometimes found in auditory cuing tasks can be distinguished empirically from
      those characterizing spatial inhibition of return (IOR), which are found in both
      target-target and go-no-go cue-target paradigms. The present work and functional
      and neurophysiological arguments all support the position that different
      mechanisms underlie spatial IOR and the inhibitory effects sometimes found in
      auditory frequency processing.

PMID- 12201338
TI  - Does node stability underlie the verbal transformation effect? A test of node
      structure theory.
AB  - Continuous repetition of a word causes listeners to hear the word transform into
      other utterances, an illusion known as the verbal transformation effect. Node
      structure theory (MacKay, 1987) provides a useful framework for understanding the
      illusion, positing that the transformations listeners report are a function of
      the stability of the node that represents the repeating stimulus. In Experiment
      1, the accuracy of this account was investigated, using stimuli that varied from
      words to phonotactically illegal pseudowords. Experiments 2 and 3 replicated and
      generalized the findings of Experiment 1, which support a conceptualization of
      node stability slightly different from that embodied in node structure theory. A
      new method of measuring lexical influences in the verbal transformation effect is
      also introduced.

PMID- 12201339
TI  - Deriving the loudness exponent from categorical judgments.
AB  - The power function exponent for loudness is traditionally determined by means of
      a process of magnitude estimation. It is demonstrated in this paper that the
      exponent can also be obtained by using the procedure of absolute identification
      of sound intensity. It has been shown that subjects' responses to tones of a
      given intensity are distributed in a normal distribution whose variance depends
      on the range, R, over which the tones are distributed. By means of a standard
      statistical transformation, the normal density in log space is converted to the
      corresponding probability density in linear space. The power function exponent
      can then be obtained directly from the linear probability density. We also
      suggest that there is a direct relationship between the information calculated
      from experiments on absolute identification of sound intensity and the
      neurophysiological, poststimulus histogram measured in a nerve fiber in the
      auditory nerve.

PMID- 12201340
TI  - The prevalence effect in two-dimensional stimulus-response compatibility is a
      function of the relative salience of the dimensions.
AB  - When stimulus-response (S-R) sets vary along horizontal and vertical dimensions,
      a right-left prevalence effect is often obtained in which the horizontal
      compatibility effect is larger than the vertical compatibility effect. Vu and
      Proctor (2001) showed that the prevalence effect varies as a function of the
      dimension made salient by the response configuration. A salient features coding
      interpretation of this result implies that manipulating the salience of the
      stimulus display should produce similar results and that S-R translation should
      be fastest when salient features of the stimulus and the response sets
      correspond. Experiment 1 manipulated spatial proximity to make the vertical or
      the horizontal stimulus dimension salient. Neutral displays yielded a typical
      right-left prevalence effect, and this effect was enhanced by horizontal-salient
      displays and eliminated by vertical-salient displays. Experiments 2 and 3 showed
      that the benefit for horizontal (or vertical) compatibility was larger when the
      salient features of both the stimulus and the response sets emphasized the
      horizontal (or the vertical) dimension than when only one did. The results
      support salient features coding as an explanation for the prevalence effect
      obtained with two-dimensional S-R arrangements.

PMID- 12201341
TI  - A reversal in the direction of detection asymmetry: effects of spatial density,
      spatial regularity, and retinal eccentricity.
AB  - We analyzed detection asymmetry, using openand closed squares as target and
      contextelements. It was found that varying density, regularity, and target
      eccentricity not only can modulate the amount of asymmetry, but also can produce
      a reversal in the direction of the asymmetry. The results suggest that the
      different stimuli are processed with different grains of analysis,consisting of
      in some cases, single elements and their properties and, in other cases, larger
      units of the stimulus array and more globalproperties. A detection task that can
      utilize the properties that are available with a given grain of analysis would
      show an advantage over a task for which the given grain of analysis is not as
      favorable, resulting indetection asymmetry in one direction or another.

PMID- 12201342
TI  - Schema-based processing in auditory scene analysis.
AB  - What is the involvement of what we know in what we perceive? In this article, the
      contribution of melodic schema-based processes to the perceptual organization of
      tone sequences is examined. Two unfamiliar six-tone melodies, one of which was
      interleaved with distractor tones, were presented successively to listeners who
      were required to decide whether the melodies were identical or different. In one
      condition, the comparison melody was presented after the mixed sequence: a target
      melody interleaved with distractor tones. In another condition, it was presented
      beforehand, so that the listeners had precise knowledge about the melody to be
      extracted from the mixture. In the latter condition, recognition performance was
      better and a bias toward same responses was reduced, as compared with the former
      condition. A third condition, in which the comparison melody presented beforehand
      was transposed up in frequency, revealed that whereas the performance improvement
      was explained in part by absolute pitch or frequency priming, relative pitch
      representation (interval and/or contour structure) may also have played a role.
      Differences in performance as a function of mean frequency separation between
      target and distractor sequences, when listeners did or did not have prior
      knowledge about the target melody, argue for a functional distinction between
      primitive and schema-based processes in auditory scene analysis.

PMID- 12201343
TI  - Negate priming and multiple repetition: a reply to Grison and Strayer (2001).
AB  - Strayer and colleagues (Grison & Strayer, 2001; Malley & Strayer 1995; Strayer &
      Grison, 1999) have reported experiments in which negative priming by ignored
      stimuli occurred onlyfor stimuli that were repeatedly sampledfrom small sets.
      These results were argued to be inconsistent with episodic/mismatch accounts of
      negative priming. We show here that a dependence of negative priming on multiple
      repetition is wholly consistent with such theories. Furthermore, we argue that
      the inhibitory theory proposed by Strayer and colleagues cannot account for major
      findings regarding negative priming and that anomalies in the data reported by
      Grison and Strayer are more parsimoniously explained by episodic/mismatch
      accounts.

PMID- 12201344
TI  - Retinal detachment in Chinese, Malay and Indian residents in Singapore: a
      comparative study on risk factors, clinical presentation and surgical outcomes.
AB  - PURPOSE: To evaluate the risk factors, clinical presentation and surgical
      outcomes of retinal detachment (RD) among Chinese, Malay and Indian residents in
      Singapore. METHODS: A retrospective descriptive study from January 1995 to
      December 1998. All RD operations performed at a tertiary ophthalmic center in
      Singapore were initially identified from a computerized audit database. Case
      records data of all Malay and Indian patients as well as a 10% randomized sample
      of Chinese patients were retrieved and analyzed. Tractional and exudative RD's
      were excluded. RESULTS: Of the Singapore residents who had a RD operation over
      the 4-year period, 597 (89.6%) were Chinese, 47 (7.1%) were Malays and 22 (3.3%)
      were Indians. The age (mean: 46.1 +/- 15.5 years), gender distribution (70.5%
      males) and presenting visual acuities were similar in the 3 races. The most
      common site of the retinal break(s) was the superotemporal retina (44.9%),
      followed by the inferotemporal retina (15.3%). Chinese patients were more likely
      to have multiple or indeterminate breaks (p = 0.09) and macula-on RD (p = 0.04),
      compared to Malays and Indians. The distribution of known risk factors (myopia,
      lattice degeneration, prior cataract surgery and prior ocular trauma) was similar
      between the three races. The majority of patients required a scleral buckling
      operation either in isolation (71.3%), or in combination with vitrectomy (19.4%),
      and only 10 (7.8%) had vitrectomies without buckles. At 6 months postoperatively,
      anatomical success (defined as an attached retina on ocular examination) and
      functional success (defined as visual acuities of 6/60 or better) were achieved
      in 108 (94.7%) and 62 patients (54.4%), respectively, with no significant racial
      variation seen. The overall rate of redetachment after the initial operation was
      low (9.3%). CONCLUSION: Variation in risk factors, clinical presentations and
      postoperative outcomes of retinal detachment appears to be minimal among Chinese,
      Malays and Indians in Singapore.

PMID- 12201346
TI  - Combined hamartoma of the retina and retinal pigment epithelium associated with
      neurofibromatosis type-1.
AB  - BACKGROUND: Retinal tumors are occasionally seen in patients with
      neurofibromatosis type-1 (NF-1). These are usually astrocytic hamartomas or
      angiomas. Combined hamartoma of the retina and retinal pigment epithelium are
      tumors also described in NF-1, but this association has not been definitively
      established yet. METHOD: We report on a child with NF-1, who presented a combined
      hamartoma of the retina and retinal pigment epithelium in both eyes. RESULTS: The
      diagnosis of bilateral combined hamartoma of the retina and retinal pigment
      epithelium in our patient was performed on the basis of the ophthalmoscopic
      appearance of the lesions. NF-1 was diagnosed following the current international
      clinical criterion, supplemented by neuroimaging findings. CONCLUSION: Despite
      the extreme rarity of this association, we believe that it is not coincidental,
      as the presence of a hamartomatous retinal lesion in a patient with a systemic
      hamartomatous neuroectodermic disease would be, at least, rational. Thus, NF-1
      must be excluded in patients with combined hamartoma of the retina and retinal
      pigment epithelium.

PMID- 12201345
TI  - Tuberculous choroidal granulomas in a patient with systemic lupus erythematosus.
      A case report.
AB  - AIM: We report a case of tuberculous choroidal granulomas in a patient with
      systemic lupus erythematosis (SLE) who developed miliary tuberculosis (TB) and
      bilateral granulomas while on immunosuppressive medication. METHODS: The case
      notes of this patient were reviewed. RESULTS: The patient was first seen for base
      line ophthalmic screening before anti-tuberculous medication was started. The
      patient was subsequently followed up at 2 weeks, 4 weeks and 2 months with fundal
      examination and photography. One choroidal granuloma was found in the right eye
      while another peripheral lesion involved the left eye. Both resolved in response
      to anti-tuberculous medication over a 2-month period with resultant chorioretinal
      atrophy and scarring. CONCLUSION: This case demonstrates the need to screen
      immuno-suppressed SLE patients who have miliary TB for possible eye involvement.

PMID- 12201347
TI  - Ageing of Schlemm's canal in nonglaucomatous subjects.
AB  - AIM: to study age-related Schlemm's canal endothelial changes and evaluate
      consequences on the filtration function. MATERIAL AND METHODS: the inner wall
      endothelium of Schlemm's canal was examined in 9 non-glaucomatous subjects aged
      between 32 and 75 years, by a combined technique of light and electron microscopy
      (scanning and transmission). Quantitative analysis included counts of bulges,
      pores, nuclei, giant vacuoles and other protruding structures, as well as
      measures of pores, giant vacuoles and Schlemm's canal size parameters (diameter
      and inner wall width). Outflow facility calculations were realised using a
      modified previously described mathematical model. RESULTS: The main structures
      affected by ageing in Schlemm's canal appeared to be giant vacuoles. Their
      density but also their size is significantly reduced with increasing age. The
      intracellular pore population is also found to diminish with age and is
      correlated to that of giant vacuoles, suggesting that those pores are luminal
      openings of vacuoles. Outflow facility calculations revealed a global decrease of
      endothelial outflow facility of about 60% between the 3rd and 7th decades. The
      study also showed a different age-related pattern for the two subtypes of
      endothelial pores. CONCLUSIONS: Our study demonstrated that Schlemm's canal
      filtration function is significantly influenced by age, as the endothelial inner
      wall outflow facility is found to be widely reduced. This is partly the result of
      an age-related reduction in counts of giant vacuoles and intracellular pores. The
      second pore population (border or intercellular) doesn't follow the same
      evolution, but may have a more significant regulator role in transendothelial
      permeability.

PMID- 12201348
TI  - Is acetazolamide effective in the treatment of diabetic macular edema? A pilot
      study.
AB  - AIM: To investigate whether acetazolamide, already found to be helpful in
      decreasing cystoid macular edema in patients with retinitis pigmentosa, was also
      effective in the treatment of diabetic macular edema in nonproliferative
      retinopathy. METHODS: Two randomized age- and sex-matched groups (cases and
      controls) of 12 diabetics (five Type 1 and seven Type 2) were selected for this
      pilot study and graded for retinopathy (Early Treatment of Diabetic Retinopathy
      Study-Airlie House Classification). Cases were treated with acetazolamide for
      three months according to a standard protocol. The Early Treatment of Diabetic
      Retinopathy Study chart was used for assessing far-best corrected visual-acuity,
      and fluorescein angiography was performed using the Heidelberg Retina Angiograph.
      The Amsler grid-test and computerized-perimetry (Octopus 2000R) were also
      performed. RESULTS: Fluorescein-angiographic findings and perimetric data
      improved significantly (p < 0.01) in the acetazolamide-treated cases compared to
      the controls while visual-acuity varied only slightly (p > 0.01). The Amsler grid
      test resulted insignificant in our study (p > 0.05). No adverse effects or
      significant variations in laboratory tests were recorded. CONCLUSION: Further
      clinical investigations involving larger numbers of patients and a longer follow
      up are required to confirm these preliminary results. However, the present study
      seems to suggest that acetazolamide could be effective in reducing fluorescein
      angiographic findings and improving perimetric data in diabetics with macular
      edema, even though the mechanism of action remains obscure. Visual-acuity varied
      only slightly.

PMID- 12201349
TI  - Unilateral retinal vasculitis, branch retinal artery occlusion and subsequent
      retinal neovascularization in Crohn's disease.
AB  - PURPOSE: To report on a case of Crohn's disease and unilateral retinal
      vasculitis, branch retinal artery occlusion and subsequent retinal
      neovascularization. METHODS: We examined a 38-year-old woman with severe left
      visual loss and biopsy-proven Crohn's disease diagnosed four years prior to the
      ocular involvement. A Heidelberg scanning laser ophthalmoscope was used for
      fundus fluorescein angiography and indocyanine green angiography. Retinal
      neovascularization was detected during the follow-up. RESULTS: Successful
      regression of retinal neovascularization was achieved after argon green laser
      panretinal photocoagulation in addition to oral steroid and salazopyrine.
      CONCLUSION: Retinal vascular involvement is a rare ocular feature of Crohn's
      disease and may result in retinal neovascularization that may necessitate prompt
      laser photocoagulation.

PMID- 12201350
TI  - Baerveldt implant in refractory glaucoma: long-term results and factors
      influencing outcome.
AB  - PURPOSE: To evaluate the clinical outcome of patients who received a Baerveldt
      implant for refractory glaucoma and to identify factors which may influence the
      outcome. METHODS: Retrospective study including 51 eyes of 51 patients with
      medically uncontrolled glaucoma who underwent Baerveldt implant surgery between
      June 1994 and December 1998. Criteria for success were intraocular pressure (IOP)
      < or = 21 mmHg and > 6 mmHg, necessity of further antiglaucoma medications,
      absence of additional glaucoma surgery and no loss of light perception. RESULTS:
      Over a mean follow-up of 37.6 (SD: +/-18.8) months, the mean intraocular pressure
      decreased from 34.8 (+/-12.5) mmHg to 14.0 (+/-4.3) mmHg at month 60. Qualified
      success rate, achieved when IOP was below 21 mmHg and higher than 6 mmHg with
      medications was 25/48 (52%), complete success rate (same IOP limits without
      medication) was 14/48 (29%). Seven eyes had major complications or lost light
      perception. Postoperative visual acuity improved or remained within one Snellen
      line of the preoperative visual acuity in 35 patients (73%). Factors associated
      with a better prognosis were a preoperative visual acuity better than 20/400 and
      etiology of glaucoma. CONCLUSION: The Baerveldt implant is effective in lowering
      intraocular pressure in most patients with refractory glaucoma. Long-term results
      are promising with satisfactory IOP control.

PMID- 12201351
TI  - Potential anti-inflammatory effects of topical retinoids and retinoid analogues.
AB  - The topical retinoid tretinoin and topical retinoid analogues such as adapalene
      and tazarotene help normalize hyperkeratinization in acne vulgaris and have
      demonstrated significant anti-inflammatory effects in experimental trials.
      Inhibition of various immune factors, including the activity of leukocytes, the
      release of proinflammatory cytokines and other mediators, and the expression of
      transcription factors and toll receptors involved in immunomodulation, has
      emerged in both in vitro studies and in vivo animal experiments. These multiple
      mechanisms of action should encourage clinicians to consider these agents in the
      first-line management of inflammatory acne lesions.

PMID- 12201352
TI  - Effect of diclofenac sodium on union of tibial fractures in rats.
AB  - Nonsteroidal anti-inflammatory drugs are often used for 7 to 10 days after
      fracture because of their effects on bone metabolism. This study evaluated the
      effect of diclofenac sodium, administered at clinical dosage and duration, on
      bone union. Fifty-four male Wistar rats were randomly and equally divided into
      three groups: control, diclofenac 1 mg, and diclofenac 2 mg. Closed diaphyseal
      fractures were induced in the right tibias of all rats; the two diclofenac groups
      received intramuscular injections in the contralateral hips for 10 days. All
      animals were immobilized in circular casts on the upper thighs. Six rats in each
      group were sacrificed at weeks 2, 4, and 6, and bony union was evaluated
      clinically, radiologically, and histologically. At the end of 2 weeks, clinical
      examinations showed subjective differences between the two treated groups and
      control animals, with more stable callus formation in controls. Radiologic
      evaluation of the callus showed numeric, but not significant, differences between
      control and treated animals. At 4 and 6 weeks, clinical and radiologic findings
      were comparable among groups. Histologically, no significant differences in
      callus formation were evident at any evaluation.

PMID- 12201353
TI  - Topiramate monotherapy in adults with newly diagnosed epilepsy.
AB  - This 6-month open-label study evaluated the efficacy and safety of topiramate
      monotherapy for partial-onset or primarily generalized seizures in 22 adults with
      newly diagnosed epilepsy. The initial topiramate dose of 25 mg could be titrated
      to a maximum effective or maximum tolerated dose of 200 mg/d. Eighteen patients
      completed the study. The mean topiramate dose was 200 mg/d (range, 75-200 mg/d).
      Compared with baseline, monthly seizure frequency decreased 89% (median), with 17
      patients (94%) achieving complete control. Five patients dropped out of the
      study. No changes in hematologic, renal, and hepatic function evaluations were
      noted, and only 1 patient experienced clinical signs significant enough to
      warrant discontinuation of treatment. In this small study, topiramate in doses
      ranging from 75 to 200 mg/d was effective and well tolerated as monotherapy in
      adults with newly diagnosed epilepsy.

PMID- 12201354
TI  - Fixed combinations of delapril plus indapamide vs fosinopril plus
      hydrochlorothiazide in mild to moderate essential hypertension.
AB  - This 12-week randomized, parallel-group, multicenter study compared fixed
      combinations of delapril (D) 30 mg plus indapamide (I) 2.5 mg and fosinopril (F)
      20 mg plus hydrochlorothiazide (H) 12.5 mg in 171 adult patients with mild to
      moderate essential hypertension. After a 2-week placebo run-in, sitting and
      standing systolic (SBP) and diastolic blood pressure (DBP) was measured by
      conventional sphygmomanometry. The primary efficacy endpoint was the percentage
      of normalized (sitting DBP < or =90 mm Hg) and responder (sitting DBP reduction
      of 10 mm Hg or DBP < or =90 mm Hg) patients. Treatment effects were analyzed in
      the intention-to-treat (ITT; n = 171) and the per-protocol (PP; n = 167)
      populations. The percentage of normalized and responder patients did not differ
      significantly between the D + I (87.4% and 92%) and the F + H (81% and 86.9%) ITT
      groups. Similar results were seen in the PP population. In ITT and PP patients,
      sitting and standing SBP and DBP values were comparable at baseline in the two
      groups and were significantly (P<.01) and similarly reduced at weeks 4, 8, and
      12. Neither treatment induced reflex tachycardia, and both regimens were well
      tolerated. Four patients in the F + H group dropped out because of adverse
      events. In this study, the efficacy and safety of D + I were comparable to those
      of F + H in patients with mild to moderate essential hypertension.

PMID- 12201355
TI  - Effect of a probiotic multivitamin compound on stress and exhaustion.
AB  - This 6-month study evaluated a probiotic multivitamin preparation in 42 adult men
      and women suffering from stress or exhaustion. The preparation was taken daily
      with breakfast. A psychological-neurologic questionnaire assessed psycho-organic,
      central vegetative, and somatic discomforts, and a validated list of adjectives
      was used to indicate the effect of therapy. At the end of the study, an overall
      40.7% improvement in stress was noted, representing significant improvements of
      17.4% in positive conditions and of 23.3% in negative conditions (both P<.001).
      In addition, decreases of 29% in the frequency of infections and of 91% in
      gastrointestinal discomforts, both established indicators of stress, were
      recorded. The preparation was well tolerated. This probiotic multivitamin is
      suitable for reducing stress or exhaustion, or both, as well as for improving the
      immune system, specifically gastrointestinal health.

PMID- 12201357
TI  - Cryptococcosis in organ transplant recipients: an overview.
AB  - Cryptococcosis is the third most common invasive fungal infection in organ
      transplant recipients after candidiasis and aspergillosis. Reports indicate that
      cryptococcosis usually presents as symptomatic disease, and despite therapy the
      mortality remains high. In addition, some data suggest that there might be
      differences in the incidence and clinical manifestations of cryptococcosis,
      depending on the specific transplant organ. The incidence of cryptococcosis in
      our transplant center is significantly higher in heart transplant recipients than
      in other transplant groups (p=0.0001). Although the primary risk factor
      contributing to cryptococcosis in organ transplant recipients is probably the
      immunosuppressive therapy used to prevent allograft rejection, environmental
      factors may also play a role. This is indicated by studies that demonstrate
      differences in the rate of cryptococcosis according to geographic region.
      Moreover, data point out differences in the isolation of the fungus from soil
      samples with higher concentrations of Cryptococcus in areas frequented by birds
      or contaminated by bird droppings. Therefore, it is prudent to recommend that
      organ transplant recipients avoid birds or areas contaminated with bird
      droppings. The current review provides an overview of the changes in the
      incidence, clinical manifestations, and management of cryptococcosis in organ
      transplant recipients.

PMID- 12201356
TI  - Preventing the common cold with a vitamin C supplement: a double-blind, placebo
      controlled survey.
AB  - One hundred sixty-eight volunteers were randomized to receive a placebo or a
      vitamin C supplement, two tablets daily, over a 60-day period between November
      and February. They used a five-point scale to assess their health and recorded
      any common cold infections and symptoms in a daily diary. Compared with the
      placebo group, the active-treatment group had significantly fewer colds (37 vs
      50, P<.05), fewer days challenged virally (85 vs 178), and a significantly
      shorter duration of severe symptoms (1.8 vs 3.1 days, P<.03). Consequently,
      volunteers in the active group were less likely to get a cold and recovered
      faster if infected. Few side effects occurred with the active treatment, and
      volunteers reported greatly increased satisfaction with the study supplement
      compared with any previous form of vitamin C. This well-tolerated vitamin C
      supplement may prevent the common cold and shorten the duration of symptoms.
      Volunteers were generally impressed by the protection afforded them during the
      winter months and the general acceptability of the study medication.

PMID- 12201358
TI  - Gene transfer of heme oxygenase-1 and carbon monoxide delivery inhibit chronic
      rejection.
AB  - The hallmark of chronic rejection is the occlusion of the artery lumen by intima
      hyperplasia as a consequence of leukocyte infiltration and vascular smooth muscle
      cell (VSMC) migration and proliferation. Heme oxygenase-1 (HO-1) is a tissue
      protective molecule which degrades heme into carbon monoxide (CO), free iron and
      biliverdin. We analyzed the effects of HO-1 gene transfer into the vessel wall
      using an adenoviral vector (AdHO-1) and of CO delivery in a model of chronic
      allogeneic aorta rejection in rats. Carbon monoxide treatment was achieved by a
      new pharmacological approach in transplantation using methylene chloride (MC),
      which releases CO after degradation. AdHO-1-mediated gene transfer into aorta
      endothelial cells (ECs) or CO delivery resulted in a significant reduction in
      intimal thickness compared to untreated or noncoding adenovirus-treated controls.
      Aortas transduced with AdHO-1 or treated with CO showed a reduction in the number
      of leukocytes as well as in the expression of adhesion molecules, costimulatory
      molecules and cytokines, with the gene transfer treatment displaying a more
      pronounced effect than the CO treatment. Conversely, CO inhibited VSMC
      accumulation in the intima more efficiently than AdHO-1 treatment. Gene transfer
      of HO-1 and pharmacological manipulation of CO are novel approaches to the
      analysis and treatment of chronic rejection.

PMID- 12201359
TI  - Optimisation of bile production during normothermic preservation of porcine
      livers.
AB  - Machine perfusion of livers may provide a mechanism for extended preservation of
      marginal donor organs before transplantation, as well as a method for viability
      assessment. It has proved possible in a series of experimental porcine liver
      perfusions to maintain liver viability for up to 72 h. However, a reduction in
      bile production with associated histological evidence of cholestasis was seen
      after 10 h of perfusion, damaging the biliary canaliculi during the preservation
      period and leaving these organs in an unacceptable condition for transplantation.
      It was proposed that reduction in bile production was the result of a relentless
      depletion of available bile salts, gut recirculation not being possible and de
      novo synthesis being unable to keep up with loss. This was proved by measuring
      porcine native bile acids within serial perfusate and bile samples using gas
      chromatography mass spectrophotometry. It was shown that all three native pig
      bile acids were decreased to 30% of their original value by 20 h of
      unsupplemented perfusion. An infusion of taurocholate managed to maintain bile
      production at physiological levels throughout the 20-h period (8 mL/h +/- 0.75).
      It was successfully incorporated by the porcine livers into bile. We propose to
      use this circuit as a novel means of preserving donor livers for transplantation
      in which the organ is maintained at normal body temperature and perfused with
      blood. This will reduce ischaemia reperfusion injury and may enable prolonged
      preservation. The modification described ensures optimal bile production over the
      entire perfusion period, preventing inspissation and subsequent damage to the
      canaliculus.

PMID- 12201360
TI  - P-selectin glycoprotein ligand-1 (rPSGL-Ig)-mediated blockade of CD62 selectin
      molecules protects rat steatotic liver grafts from ischemia/reperfusion injury.
AB  - We examined the effects of early blockade of CD62 selectin-mediated adhesive
      interactions in steatotic rat liver models of ex vivo cold ischemia followed by
      reperfusion or transplantation by administration of P-selectin glycoprotein
      ligand-1 (rPSGL-Ig). In the model of cold ischemia/reperfusion, livers pretreated
      ex vivo with rPSGL-Ig at harvesting from obese Zucker rats showed significantly
      decreased portal resistance, increased bile production, and diminished hepatic
      endothelial neutrophil infiltration, as compared with untreated controls.
      Pretreatment of fatty livers with rPSGL-Ig prior to transplantation extended the
      survival of lean Zucker rat recipients from 40% to 90%. This effect correlated
      with significantly improved liver function, depressed neutrophil activity, and
      decreased histologic features of hepatocyte injury. Intragraft expression of CD62
      P-selectin was similar in both recipient groups. rPSGL-Ig treatment decreased
      intragraft infiltration by CD3/CD25 cells, diminished expression of pro
      inflammatory TNFalpha, IL-6, iNOS, IL-2 and IFN-gamma, without significantly
      affecting mRNA levels coding for anti-inflammatory IL-4. Thus, rPSGL-Ig blockade
      of CD62-mediated adhesive interactions protects against severe
      ischemia/reperfusion injury suffered otherwise by steatotic rat livers. These
      findings document the potential utility of rPSGL-Ig in increasing the transplant
      donor pool through modulation of marginal steatotic livers.

PMID- 12201361
TI  - Normal donor bone marrow is superior to Flt3 ligand-mobilized bone marrow in
      prolonging heart allograft survival when combined with anti-CD40L (CD154).
AB  - Flt3 ligand (FL) administration markedly increases bone marrow (BM) stem cells
      and immature dendritic cells. We investigated the influence of CD40-CD40Ligand
      (CD154) pathway blockade on antidonor immunity, cytokine production,
      microchimerism and heart graft survival in BALB/c (H2d) recipients of fully
      allogeneic C57BL/10 (H2b) FL-mobilized BM (FL-BM) or normal BM. Anti-CD40L mAb
      strongly suppressed anti-donor T-cell proliferative responses in recipients of
      either normal or FL-BM, but was less efficient in inhibiting antidonor cytolytic
      T-cell (CTL) activity, especially in recipients of FL-BM. Interestingly, CD40L
      blockade was more effective in recipients of multiple compared with single donor
      BM infusions. Anti-donor cytokine responses revealed complete impairment of IFN
      gamma, IL-4 and IL-10 production in recipients of normal BM and CD40L mAb. By
      contrast, and in agreement with the CTL data, mice given FL-BM retained ability
      to produce IFN-gamma CD40-CD40L blockade did not promote microchimerism, as
      evidenced by immunohistology and real time polymerase chain reaction.
      Nevertheless, anti-CD40L mAb enhanced heart allograft survival in recipients of
      FL-BM, but the effect was inferior to that achieved with normal BM. These data
      provide insight into the influence of growth factor-expanded donor BM and
      costimulation blockade on antidonor immune reactivity and transplant outcome. The
      comparatively poor outcome obtained using FL-BM plus anti-CD40L mAb in this model
      may be ascribed to the failure of effectively interdicting antidonor CTL
      activity.

PMID- 12201362
TI  - CD2 is a dominant target for allogeneic responses.
AB  - CD2 and 2B4 (CD244) are members of the immunoglobulin gene superfamily and are
      both ligands for another family member, CD48. CD2 is widely distributed on T, NK,
      and B cells and some antigen-presenting cells, while 2B4 is expressed on NK and
      some T cells and monocytes and is known to participate in NK cytotoxicity. Since
      indefinite allograft survival could be obtained by a combination of anti-CD48
      plus anti-CD2 mAb administration, it was important to determine the role of 2B4
      blockade in allograft rejection. MAbs directed against CD2, CD48, or 2B4 were
      administered singly or in pairs to cardiac allograft recipients. The experiments
      show that only anti-CD2 plus anti-CD48 mAbs result in indefinite allograft
      survival, while anti-CD2 plus anti-2B4 mAbs substantially prolong graft survival,
      and anti-CD48 plus anti-2B4 mAbs were no better than each mAb alone. The effect
      of these mAbs on anti-CD3 mAb and alloantigen-driven proliferation and IFN-gamma
      production were also assessed. In general, anti-CD2 inhibited both anti-CD3 mAb
      and alloantigen-driven responses, while anti-CD48 inhibited only anti-CD3 mAb but
      not alloantigen-driven proliferative and cytokine responses. Anti-2B4 mAbs were
      generally ineffective alone. Combinations of mAbs were more effective than single
      mAbs only in alloantigen-driven proliferation, commensurate with allograft
      survival results. Using CD2-/- and CD48-/- T cells and antigen-presenting cells,
      we also demonstrate that these inhibitory mAbs act primarily by blocking
      intercellular interactions, rather than directly delivering negative signals to T
      cells. These results suggest that, unlike CD2, 2B4 is not a potent regulatory
      molecule or ligand for CD48 in the response to alloantigen. Blocking the 2B4-CD48
      receptor-ligand pair does not inhibit T-cell responses and alloreactivity to the
      same degree as CD2-CD48 blockade.

PMID- 12201363
TI  - Accumulation of crystal deposits in abdominal organs following perfusion with
      defrosted University of Wisconsin solutions.
AB  - Previous studies reported on both visible and invisible particles in University
      of Wisconsin (UW) solutions. Those particles originated from components of the
      bags. In recent clinical observations we noticed macroscopically visible,
      indissoluble particles in UW bags reaching subzero temperatures during
      transportation of organs and preservation solutions. In an experimental model we
      examined whether those particles could be detected following perfusion of
      abdominal organs with established perfusion solutions. UW-, HTK- or physiological
      saline solutions reached -3 +/- 0.5 degrees C under conditions frequently applied
      during transportation. UW solutions demonstrated the accumulation of visible,
      indissoluble crystals and were subsequently used for the perfusion of abdominal
      organs in LEW rats. After perfusion with UW solutions stored at freezing
      temperatures, crystals were detected in all abdominal organs localized in and
      around vessels, bile ducts, glomeruli and in the interstitium of harvested
      livers, kidneys and pancreas. By spectroscopy, we were able to characterize
      crystals as adenosine. A 40-microm pore-size filter eliminated crystals from UW
      solutions. Crystals were absent in organs perfused with HTK- or saline solutions
      kept at subzero conditions. UW solutions can reach subzero temperatures under
      commonly used transportation conditions. Under these conditions, visible crystals
      accumulate and can be detected in abdominal organs of an experimental system.

PMID- 12201364
TI  - Cold induces catalytic iron release of cytochrome P-450 origin: a critical step
      in cold storage-induced renal injury.
AB  - Earlier experimental studies have suggested a role for iron in cold-storage
      induced organ injury. Whether the cytochrome P-450 enzymes, shown to be a source
      for iron in several injury models, contribute to cold-induced iron release is not
      known. Storage of human proximal tubular epithelial (RPTE) cells at 4 degrees C
      in the University of Wisconsin (UW) solution caused a significant and time
      dependent increase in bleomycin-detectable iron (BDI). To identify the cellular
      source of BDI, RPTE cells were subfractionated and stored at 4 degrees C for 4 h.
      Bleomycin-detectable iron release was highest in the microsomes, next in the
      cytosol and none in the mitochondria. As microsomes are rich in iron-containing
      cytochrome P-450 enzymes, microsomes were cold stored with P-450 inhibitors,
      cimetidine and piperonyl butoxide. P-450 inhibitors significantly reduced cold
      induced BDI release. Furthermore, cimetidine and iron chelator deferoxamine (DFO)
      significantly reduced cold-induced cell injury, suggesting a role for P-450
      derived iron in cold-induced cell injury. In rat kidney experiments, BDI and LDH
      release were significantly higher in cold-stored kidneys than in control kidneys.
      Inclusion of cimetidine and DFO in the cold-storage solution significantly
      suppressed the BDI and LDH release, and reduced the ultrastructural changes. Our
      data demonstrate for the first time that cold-induced catalytic iron release may
      be at least in part of microsomal cytochrome P-450 origin, and that it
      participates in cold-storage-induced renal injury. In the clinical setting,
      sequestering free iron released during cold storage is possible and may prove to
      be useful in limiting organ injury.

PMID- 12201365
TI  - The impact of polymorphisms in chemokine and chemokine receptors on outcomes in
      liver transplantation.
AB  - Chemokines and their corresponding receptors likely play a central role in
      directing mononuclear cells to the graft sites during rejection. Genes for the
      chemokine stromal derived factor-1 (SDF1) and CC chemokine receptors CCR2 and
      CCR5 are characterized by polymorphisms which alter their function. We genotyped
      DNA of 207 liver transplant recipients by PCR or PCR-RFLP for CCR2-641,
      CCR5delta32, and SDF1-3'A polymorphisms, and examined their association on
      outcomes in liver allograft recipients. Due to the low number of patients
      homozygous for CCR2-641 and CCR5delta32, only the effects of their heterozygous
      variants were addressed in this study. None of the investigated polymorphisms
      showed a significant shift in gene frequency in acute rejection and rejection
      free groups, or for graft survival. The gene frequency of the SDF1-3'A allele was
      significantly (p = 0.034) higher in patients who died (29.0%, n = 31) compared to
      recipients still alive (17.1%, n = 172). The mean patient survival time post
      transplant was 134 months in patients with SDF1 wild-type, significantly (log
      rank p = 0.014) longer than 98 months in patients with at least one SDF1-3'A
      allele. The CCR2 and CCR5 polymorphisms were not associated with significant
      differences in mortality rate. In conclusion, CCR2-641, CCR5delta32, and SDF1-3'A
      genotypes did not influence the risk for acute rejection or graft survival.
      However, in liver allograft recipients SDF1-3'A is significantly associated with
      higher mortality.

PMID- 12201366
TI  - Short-term bridge to heart transplant using the BVS 5000 external ventricular
      assist device.
AB  - From January 1995 to April 2001, 71 patients with cardiogenic shock using the BVS
      5000 were treated or accepted in transfer. Of the 24 transplanted, nine had
      dilated cardiomyopathy, ischemic cardiomyopathy, acute myocardial infarction,
      giant cell myocarditis and previous Fontan procedure (group I, n = 13). The
      others had postcardiotomy shock (group II, n = 11); seven were transferred to our
      center after device implantation. Age ranged from 8 to 67 years. Ten (77%)
      patients in group I were implanted without cardiopulmonary bypass. The mean
      duration of support was 6.7 (2-24) d. Twelve patients were extubated before
      transplantation and 13 (five in group I, eight in group II) received nonstandard
      donor organs. Survival to discharge and 1-year actuarial survival was 85 and 77%
      for group I and 73 and 64% for group II, respectively. Patients with post-implant
      serum bilirubin levels > 10 mg/dL had a tendency to expire from multiple systemic
      organ failure. Patients not ventilator-dependent at the time of transplant had
      the best outcomes. Short-term bridge to transplantation using the BVS 5000 is
      feasible in selected patients. Caution is recommended when directing such
      patients to transplant if they need ventilator support and have high serum
      bilirubin levels.

PMID- 12201367
TI  - Decline in renal function following thoracic organ transplantation in children.
AB  - Heart and/or lung transplantation are life-saving treatments for end-stage
      cardiopulmonary disease; however, chronic renal failure may develop. The impact
      of thoracic organ transplant on renal function in infants and children is not
      well characterized. This retrospective cohort study evaluated renal function
      following thoracic organ transplantation in 46 children (32 heart, 9 lung, 5
      heart-lung; median age 4.1 years) with at least 12 months of follow-up.
      Glomerular filtration rate (GFR, ml/min/1.73 m2) was estimated by the Schwartz
      formula throughout and each GFR estimate was converted to per cent normal for age
      (GFR%). Changes in renal function following transplantation were analyzed using
      longitudinal mixed-effects linear regression models. GFR% decreased following
      thoracic organ transplantation (p <0.001). Younger age at transplant was
      associated with a greater decline in GFR% (p <0.01). The decline in GFR%
      persisted after adjustment for nutritional status with body mass index or weight
      for-length z-scores. The prevalence of renal insufficiency (GFR% <75) increased
      from 22% at transplant to 55% and 85% at 1 and 5 years post transplant,
      respectively, while 15% had a GFR% <50 at 5 years post transplantation. Higher
      tacrolimus trough levels over the first 6 months correlated with a lower GFR% (p
      <0.01). Renal function declined significantly following thoracic organ
      transplantation.

PMID- 12201368
TI  - Human T-cell lymphotrophic virus infection in organ donors: a need to reassess
      policy?
AB  - Human T-cell lymphotrophic virus (HTLV)-I/II infection has been considered a
      contra-indication to organ donation due to the risk of transmission of infection
      and the subsequent development of either adult T-cell leukemia or HTLV-I
      associated myelopathy. However, neither the incidence of HTLV-I/II infection in
      organ donors nor the risk of transmission of HTLV-I/II by solid organ
      transplantation has been defined. Further, it is not known if HTLV infection
      contributes to significant morbidity in solid organ recipients. The purpose of
      this study was to evaluate the incidence of HTLV-I/II infection in organ donors
      in USA and to determine if transplanting these organs resulted in HTLV-related
      morbidity or mortality. We utilized the UNOS database to: (i) identify organ
      donors that were positive for HTLV-I or II infection between 1988 and 2000, and
      (ii) evaluate outcomes in the recipients of these organs. There were 25 HTLV-I/II
      positive organ donors reported to UNOS between 1988 and 2000. Based on organ
      donors with a known HTLV-I/II status, the prevalence of HTLV-I infection in organ
      donors is 0.027% and the prevalence of HTLV-II is 0.064%. Twenty-two organs were
      transplanted from these HTLV-positive donors. There have been no reports of HTLV
      I/II-related disease in the recipients with a median follow-up of 11.9 months. At
      our center, over the last 1.5 years there have been four multiorgan donors with
      false-positive HTLV-I/II screening assays, which resulted in the decision not to
      use organs from these donors. Based on the minimal chance of HTLV-related disease
      following transplantation of HTLV-I/II organs in this series, we recommend that
      careful consideration be given to transplanting organs from HTLV-I/II-positive
      organ donors.

PMID- 12201369
TI  - Evaluation of the Eurotransplant Senior Program. The results of the first year.
AB  - On 4 January 1999, the Eurotransplant Senior Program (ESP) was implemented within
      the Eurotransplant kidney allocation scheme. PATIENTS AND METHODS: Kidneys
      obtained from donors aged over 65 years of age (65+) were allocated to a selected
      group of nonimmunized 65+ patients undergoing their first transplant. All
      transplants were performed locally to minimize cold-ischemic time. All
      transplants performed with kidneys from elderly donors that were allocated via
      ESP (ESP group) were compared to transplants performed with similar kidneys
      allocated via the standard renal allocation system (control group). Initial
      kidney function and 1-year graft outcome were assessed. RESULTS: In 1999, 227 ESP
      and 102 control transplants were performed. The duration of cold-ischemic time
      was 12 and 19 h for the ESP and control groups, respectively. No rejection
      episodes occurred in 60% and 67% of the ESP patients and controls, respectively,
      while a direct kidney function was observed in 59% of ESP and 49% of control
      patients. The 1-year graft survival rates, censoring for graft losses due to
      deaths in patients with functioning grafts, were 86% and 79%, respectively.
      CONCLUSION: An old-for-old renal allocation algorithm can be successful provided
      that risk factors, such as cold-ischemic time, are reduced.

PMID- 12201370
TI  - Treatment of active cytomegalovirus disease with oral ganciclovir in renal
      allograft recipients: monitoring efficacy with quantitative cytomegalovirus
      polymerase chain reaction.
AB  - Treatment regimens of patients with active cytomegalovirus (CMV) disease require
      2-3 weeks of intravenous ganciclovir (GCV) with/without CMV hyperimmune globulin.
      Oral GCV is effective as a prophylactic agent in prevention of CMV disease. Here
      we explored the utility of oral GCV as a treatment of active CMV disease. Fifteen
      renal allograft recipients (CMV donor+/recipient- [53%], CMV donor+/recipient+
      [40%] or CMV donor-/recipient+ [7%]) developed active CMV disease.
      Cytomegalovirus polymerase chain reaction (CMV-PCR) tests were performed at the
      time of presentation and patients were treated with oral ganciclovir 1 g tid
      (adjusted for renal function). Patients were monitored for efficacy of treatment
      by assessment of clinical symptoms and CMV-PCR. Treatment was continued until the
      CMV-PCR copy number was negative and symptoms resolved. The mean CMV-PCR copy
      number at the time of diagnosis was 580 copies/microg DNA (nl: < 5 copies/microg
      DNA). After 5-7 days of treatment, the mean copy number was 65 copies/microg DNA.
      Fourteen of 15 patients responded well to oral ganciclovir, with complete
      resolution of clinical symptoms and eradication of CMV-PCR positivity. One
      patient did not respond to oral ganciclovir therapy due to probable
      noncompliance. Our data suggest that oral ganciclovir treatment, coupled with
      careful CMV-PCR monitoring, may be a reasonable alternative to long-term
      intravenous ganciclovir.

PMID- 12201371
TI  - Sequential kidney/islet transplantation using prednisone-free immunosuppression.
AB  - Islet transplantation is becoming established as a treatment option for type I
      diabetes in select patients. Individuals with type I diabetes who have previously
      received a successful kidney allograft may be good candidates for islet
      transplantation. They have already assumed the risks of chronic
      immunosuppression, so the added procedural risk of a subsequent islet transplant
      would be minimal. Furthermore, because of the preimmunosuppressed state it is
      possible that islet-after-kidney transplantation may result in a more efficient
      early islet engraftment. Consequently, insulin independence might be achieved
      with significantly fewer islets than the approximately 8-10,000 islet
      equivalents/kg/b.w. currently required. A mass that usually demands two or more
      cadaveric donors. A case of successful islet-after-kidney transplantation is
      described using the steroid-free Edmonton immunosuppression protocol.
      Characteristics of the final islet product are: a) islet equivalents: 265,888
      (4100 islet equivalents/kg/b.w.); b) islet purity: 75-80%; c) viability: >95%
      (trypan blue exclusion); and d) mean islet potency (static low-high glucose
      challenge): 4.16 +/- 1.91-fold increase. Post-transplant the patient's
      hypoglycemic episodes abated. Exogenous insulin requirements were eliminated at
      week 12 post-transplant as basal and Ensure (Abbott Laboratories, Abbott Park,
      IL, USA) oral glucose stimulated C-peptide levels peaked and stabilized. Twenty
      four-hour continuous glucose monitoring confirmed moment-to-moment glycemic
      control, and periodic nonfasting finger stick glucose determinations over the
      next month confirmed glycemia was controlled. Hemoglobin A1c levels declined from
      a pretransplant level of 6.9% to 5.3%. Renal allograft function remained changed.

PMID- 12201372
TI  - Primary cutaneous fungal infections in solid organ transplantation: a case
      series.
AB  - Cutaneous fungal infections in solid-organ transplant patients present in a
      variety of nonspecific ways, requiring a high index of suspicion to diagnose
      correctly. In the present series of four transplant recipients, subsequent
      primary cutaneous fungal infections presented as papules, plaques, ulcers and
      subcutaneous nodules. Transplantations included one cardiac, two renal and one
      renal-pancreatic transplant. Fungal infections were limited to the skin; there
      was no evidence of disseminated disease in any case. The pathogens isolated were
      Scedosporium apiospermum (Pseudallescheria boydii), Alternaria species,
      Aspergillus fumigatus, and a coelomycete in the Coniothyrium-Microsphaeropsis
      complex of dark molds. Individuals were successfully treated with surgical
      debridement, antifungal agents, and reduction of immunosuppressive therapy. All
      patients and allografts survived. Accurate diagnosis, aggressive surgery and
      appropriate antifungal therapy, combined with close outpatient follow-up,
      optimize the likelihood of a cure in a transplant population.

PMID- 12201374
TI  - Hypothermic perfusion of the warm ischemic kidney: is 32 degrees C better than 4
      degrees C?

PMID- 12201373
TI  - Cytomegalovirus-induced glomerular vasculopathy in renal allografts: a report of
      two cases.
AB  - Cytomegalovirus (CMV) remains a major viral pathogen complicating renal
      transplantation. Tubulointerstitial nephritis is the commonly acknowledged and
      well-characterized pathologic feature of renal allograft CMV disease. There is
      controversy about whether there is a distinct entity as a CMV glomerulopathy in
      the absence of tubulointerstitial disease. We describe two patients with renal
      allograft dysfunction who displayed distinct features of CMV glomerular
      vasculopathy, in the absence of overt viral cytopathic changes involving the
      tubules.

PMID- 12201375
TI  - Temporal sequencing of alcohol-related problems, problem recognition, and help
      seeking episodes.
AB  - Little is known about temporal relations between the development of alcohol
      related problems, self-recognition of problems, and help seeking from
      professional and lay sources. The sequencing of these events was investigated
      retrospectively using a community sample of male and female problem drinkers (N=
      101) who varied in their help-seeking histories [no assistance, Alcoholics
      Anonymous (AA)-only, or treatment-plus-AA] and current drinking status (resolved
      abstinent or nonresolved). The rank-order of events was similar across groups and
      gender. Problem recognition typically occurred early with the onset of
      pathological drinking and related psychosocial problems. Health problems and help
      seeking were late developments, if they occurred at all. Although the sequence
      order was similar across groups, the latency to help seeking varied; help seeking
      was more rapid among women, resolved participants, and participants who had
      sought help from both treatment and AA. The findings question conventional views
      that denial deters help seeking and suggest opportunities for screening and early
      intervention.

PMID- 12201376
TI  - Initial validation of two opiate craving questionnaires the obsessive compulsive
      drug use scale and the desires for drug questionnaire.
AB  - In the present study, the factor structure, internal consistency, and the
      concurrent validity of two heroin craving questionnaires are examined. The
      Desires for Drug Questionnaire (DDQ) measures three factors: desire and
      intention, negative reinforcement, and control. The Obsessive Compulsive Drug Use
      Scale (OCDUS) also measures three factors: thoughts about heroin and
      interference, desire and control, and resistance to thoughts and intention.
      Subjects were 102 Dutch patients who were currently in treatment for drug
      dependency. All proposed scales have good reliability and concurrent validity.
      Implementation of these instruments in both clinical and research field is
      advocated.

PMID- 12201377
TI  - Utility and accuracy of collateral reports of smoking status among 256 abstinent
      alcoholic smokers treated for smoking cessation.
AB  - This study examined the utility and accuracy of collateral reports of smoking
      status among 256 abstinent alcoholic smokers (140 males, 116 females) treated for
      smoking cessation. Data were gathered prospectively from two randomized clinical
      trials of behavioral smoking cessation treatment conducted in San Diego, CA. The
      mean age of the participants was 42.0 years (S.D.= 10.0) and 93% were Caucasian.
      Self-reported smoking status was obtained at posttreatment (1 week after the
      target quit date) and at 1 year. Collateral reports obtained by telephone and
      expired air carbon monoxide (CO) levels of < 10 ppm were used to confirm self
      reported smoking status. Collateral reports were available for 89.1% of subjects
      at posttreatment and 90.6% of subjects at 1 year. The smoking abstinence rates
      were similar when using collateral reports or CO confirmation of smoking status
      at both time points. Collateral reports refuted self-reported abstinence as often
      or more than CO levels, and showed relatively high concordance with CO levels. In
      conclusion, collateral reports have utility and are reasonably accurate for
      confirming self-reported smoking status in clinical trials of smoking cessation
      for abstinent alcoholic smokers.

PMID- 12201378
TI  - Predicting initiation of smoking in adolescents: evidence for integrating the
      stages of change and susceptibility to smoking constructs.
AB  - We examined the concurrent and predictive validity of stages of change and
      susceptibility to smoking with respect to smoking onset among adolescents. We
      also sought to determine whether concurrent use of the two constructs, in the
      form of an integrated stage/susceptibility index, would predict adolescent
      smoking acquisition better than eithe r construct alone. Data were examinedfrom
      two study populations: a prospective study of 1,124 elementary-school through
      senior-high-school students and a cross-sectional study of 5,624 high-school
      students. Both constructs demonstrated good concurrent and predictive validity. A
      measure integrating the stages of smoking acquisition and susceptibility to
      smoking constructs was created by dividing the precontemplation group as a
      function of susceptibility. This new classification system yielded better
      concurrent and predictive validity than did either stage of smoking acquisition
      or susceptibility to smoking alone.

PMID- 12201379
TI  - Adverse childhood experiences and personal alcohol abuse as an adult.
AB  - Adult alcohol abuse has been linked to childhood abuse and family dysfunction.
      However, little information is available about the contribution of multiple
      adverse childhood experiences (ACEs) in combination with parental alcohol abuse,
      to the risk of later alcohol abuse. A questionnaire about childhood abuse,
      parental alcoholism and family dysfunction while growing up was completed by
      adult HMO members in order to retrospectively assess the independent relationship
      of eight ACEs to the risk of adult alcohol abuse. The number of ACEs was used in
      stratified logistic regression models to assess their impact on several adult
      alcohol problems in the presence or absence of parental alcoholism. Each of the
      eight individual ACEs was associated with a higher risk alcohol abuse as an
      adult. Compared to persons with no ACEs, the risk of heavy drinking, self
      reported alcoholism, and marrying an alcoholic were increased twofold to fourfold
      by the presence of multiple ACEs, regardless of parental alcoholism. Prevention
      of ACEs and treatment of persons affected by them may reduce the occurrence of
      adult alcohol problems.

PMID- 12201380
TI  - Alcohol and HIV risk taking among intravenous drug users.
AB  - PURPOSE: To determine if drug risk days are also alcohol use days for active
      injection drug users (IDUs). METHODS: Cross-sectional interview of 187 AUDIT
      positive (> or = 8) active IDUs recruited between 2/98 and 10/99 from a needle
      exchange program (NEP) in Providence, RI. A drug risk day is defined as "using
      needles, cotton, or cookers after someone else had used it," measured using a 30
      day Timeline Follow-Back procedure. RESULTS: The sample was 64% male, 87% white,
      with 85% meeting DSM-IV criteria for alcohol abuse/dependence. Of the total days
      analyzed (n = 5610), 25% were drug risk days; on 40% of these days, drinking also
      occurred. Using a generalized estimating equation (GEE) model to cluster by
      subject, alcohol use was associated with drug risk days (OR 1.53; 95% CI 1.2-1.9;
      P < .001), controlling for gender, age, race, cocaine use, number of daily
      injections, methadone treatment, and partner drug use. CONCLUSIONS: Using a data
      analytic strategy that allows examination of self-reports of behaviors on a day
      to-day basis, we found that alcohol use is associated with drug risk taking
      behavior among IDUs. Whether alcohol use precedes or is subsequent to risky HIV
      behaviors remains to be determined.

PMID- 12201381
TI  - Screening for health behaviors in ambulatory clinical settings: does smoking
      status predict hazardous drinking?
AB  - Although a link between alcohol consumption and smoking behavior is well
      documented, the majority of studies have focused on individuals dependent on both
      alcohol and nicotine. The present study examined the likelihood of hazardous
      drinking as a function of smoking status, gender, age, ethnicity, and education
      in a sample of 676 medical and dental patients whose drinking covered the
      spectrum from abstinence to high levels. We hypothesized that hazardous drinking
      would be more common among young, male respondents who were current smokers and
      that past smokers would show a risk of hazardous drinking that was intermediate
      between that of current smokers and nonsmokers. Results showed that younger age,
      fewer years of education, male gender, and current smoking status were
      significant predictors of hazardous drinking. However, there was no relationship
      between a past history of smoking and current risk of hazardous drinking.
      Evaluation of the Fagerstrom Tolerance Questionnaire (FTQ) showed that it was no
      more useful as a screening instrument than a single question that elicited
      current smoking status. These findings suggest that patients who report current
      smoking should routinely be asked about their current alcohol consumption.
      Interventions should then be tailored to address smoking and, if appropriate,
      hazardous drinking as well.

PMID- 12201382
TI  - Substance abuse treatment outcomes for cognitively impaired and intact
      outpatients.
AB  - The purpose of this research was to examine the effects of cognitive impairment
      on the efficacy of substance abuse treatment outcome. Alcohol, drug, medical,
      legal, psychological, employment, and family functioning related treatment
      outcomes were examined for 26 cognitively impaired and 68 cognitively intact
      abusing outpatients. Subjects were enrolled in an intensive, 3-week, outpatient
      program for the treatment of their substance abuse. Subjects were administered a
      battery of neuropsychological tests prior to treatment onset, and outcome data
      were obtained at 1, 3, 6, and 12 months posttreatment entry. No significant
      between-group differences were found on any of the outcome measures, and
      significant treatment gains were observed across all problem domains in both
      groups. Subjects' largest improvements were made in the first month of treatment
      for alcohol, drug, legal, family, and psychological problems. Improvements for
      employment and medical problems were not observed until 6 months posttreatment.
      Success across domains was maintained through 12 months follow-up, with the
      exception of psychological problems; 12-month data indicated a return to thelevel
      observed at 30 days posttreatment for psychological problems, a level that
      reflected significant improvement from baseline functioning. A greater proportion
      of treatment dropouts (i.e., no follow-up data obtained after 30 days) were
      cognitively impaired as compared to treatment completers. These results suggest
      that this method of intensive substance abuse outpatient treatment is effective
      for cognitively impaired patients, an important finding given that research
      evaluating the efficacy of interventions for such patients is limited.
      Additionally, neuropsychological evaluation may be important in reducing
      treatment dropouts, as the present findings indicated that greater cognitive
      impairment was related to an increased likelihood of treatment dropout.

PMID- 12201383
TI  - Treating an opiate-dependent inpatient population: a one-year follow-up study of
      treatment completers and noncompleters.
AB  - INTRODUCTION: The aim of this study was to compare the characteristics of
      patients who completed (completers) inpatient treatment of drug dependence with
      those who failed to complete this programme (noncompleters). METHOD: Participants
      were assessed at admission using the Substance Abuse Assessment Questionnaire
      (SAAQ) to obtain information about the sociodemographic background, history of
      drug and alcohol use, physical health, mental health, offending behaviour, and
      interpersonal relationships. Follow-up interviews were carried out 3, 6, 9, and
      12 months after discharge using the SAAQ-Follow-up. To form the three comparison
      groups, participants were divided on the basis of completion of detoxification
      and receipt of aftercare. RESULTS AND CONCLUSIONS: Significantly better treatment
      outcome was observed amongst those who completed detoxification and went on to
      spend at least 6 weeks in a recovery and/or residential rehabilitation unit. In
      contrast, there were no significant differences between noncompleters and
      completers who had no aftercare on the majority of measures of drug use during
      follow-up.

PMID- 12201384
TI  - Interactions between psychotherapy procedures and patient attributes that predict
      alcohol treatment effectiveness: a preliminary report.
AB  - This study examined interactions between patient attributes and therapist
      interventions on alcoholism treatment outcome. Process analyses of an early
      psychotherapy session from either cognitive-behavioral (CBT) or family systems
      (FST) therapy and baseline patient information (N=47) were used to measure theory
      based therapy and patient variables. Hierarchical linear regression was used to
      test the effect of each patient-therapy interaction on changes in drinking
      behavior. Two disordinal interactions were predictors of alcohol use during the
      maintenance phase of treatment. Patients high in emotional distress did best when
      their therapy addressed emotional experiences, and the converse was observed for
      patients low in distress. Patients high in reactance had better drinking outcomes
      when their therapy was nondirective, and patients low in reactance improved more
      with directive therapy. In contrast to the interactions between patient
      attributes and the therapy process, the interactions between patient attributes
      and treatment model (CBT versus FST) were not reliable predictors of alcohol use.

PMID- 12201385
TI  - Prior cigarette smoking initiation predicting current alcohol use: evidence for a
      gateway drug effect among California adolescents from eleven ethnic groups.
AB  - Gateway drug theory provides a useful framework for understanding drug use among
      adolescent populations. Studies have reported a gateway effect of cigarette
      smoking on alcohol use among adolescents; but there is a lack of knowledge
      regarding ethnic differences in this effect. Using data from a cross-sectional
      survey in California, 11,239 subjects (46.3% male) from 31 high schools with at
      least 25% of total enrollment of Asian and at least 200 students with Asian
      ancestry entered the analysis. Among them, 6016 were ninth graders (mean
      age=14.3, S.D.=0.49) and 5223 were twelfth graders (mean age=17.3, S.D.=0.54).
      After controlling for seven variables, the risk ratio of last 30-day alcohol use
      among prior smoking initiators vs. noninitiators was 5.82 for non-Hispanic
      Whites, 4.25 for Blacks, 8.37 for Asian Indians, 3.99 for Chinese, 3.45 for
      Filipinos, 3.48 for Japanese, 5.41 for Koreans, 7.57 for Vietnamese, 4.02 for
      Mexicans, 2.64 for South/Central Americans, and 5.95 for adolescents with
      multiethnic background. Comparison of the 11 ethnic groups indicated that
      adolescents from different ethnic groups but with similar cultural background had
      a similar risk level; such pattern existed after controlling for acculturation,
      parents' monitoring, and school performance. The risk ratio did not differ by
      gender and grade. There is an association between prior cigarette smoking
      initiation and current alcohol use among adolescents from different ethnic
      backgrounds, including those of multiethnicity, which supports the
      generalizability of gateway drug effect of cigarette smoking on alcohol use.
      Studies should be conducted to investigate factors attributable to the ethnic
      variations of this association.

PMID- 12201386
TI  - A laboratory-based investigation of relations among video lottery terminal (VLT)
      play, negative mood, and alcohol consumption in regular VLT players.
AB  - Thirty regular video lottery terminal (VLT) players were randomly assigned to 90
      min of VLT play or a control activity (viewing a movie) to examine the impact of
      VLT play on alcohol use. Ratings of dysphoric mood were taken at baseline,
      midactivity, and postactivity. Alcoholic and nonalcoholic control beverages were
      available throughout. As hypothesized, those in the VLT condition were more
      likely to consume alcoholic than nonalcoholic control beverages (i.e., 73% drank
      alcohol and 20% drank control beverages), whereas no such preference for alcohol
      was observed in the movie control condition (i.e., 40% drank alcohol and 47%
      drank control beverages). Consistentwith predictions derived from Steele and
      Josephs' [J. Abnorm. Psychol. 97 (1988) 196; Am. Psychol. 45 (1990) 921.]
      attention allocation model, VLT condition participants who drank alcohol showed
      increases in dysphoric effect over the course of testing. No such changes in
      negative mood were observed in VLT participants who did not consume alcohol or in
      movie control participants regardless of whether they drank alcohol. An observed
      temporal pattern of greater drinking during the early phase of VLT play indicated
      that the relation between alcohol use and dysphoric affect among VLT condition
      participants could not readily be explained by drinking to relieve dysphoria
      induced by VLT losses. Clinical and policy implications are discussed.

PMID- 12201387
TI  - Comorbidity among Oxford House residents: a preliminary outcome study.
AB  - This study used a structured diagnostic interview to investigate the prevalence
      of psychiatric comorbidity among 29 men and 23 women substance abusers residing
      in 1 of 11 Oxford House communities located within a Midwestern metropolitan
      area. The Diagnostic Interview Schedule (DIS) was used to measure current and
      lifetime DSM-III-R diagnosis in addition to sociodemographic and substance abuse
      information. Considerable psychiatric comorbidity was present. Antisocial
      personality (ASP) disorder, affective disorders, and anxiety disorders were the
      most frequently observed comorbid disorders among these substance abusers, whose
      drugs of choice were cocaine, alcohol, and cannabis. Chi-square and t tests
      revealed diverse psychiatric diagnoses and variability of client characteristics,
      demonstrating heterogeneity within this sample of substance abusers. Gender
      differences were identified on several client characteristics as well. Peer
      social support was the most common reason why participants entered an Oxford
      House. Outcome measures at 6 months found that 42% of participants was still
      residing in an Oxford House while 27% left on good terms, demonstrating a 69%
      overall success rate among participants in this study. Implications of this study
      suggest that substance abusers with psychiatric comorbidity are heterogeneous
      groups that benefit from living in an Oxford House.

PMID- 12201388
TI  - Auditing patient experience and satisfaction.

PMID- 12201389
TI  - Paediatric neurosurgery in the United Kingdom: reports and models for provision.

PMID- 12201390
TI  - Safe paediatric neurosurgery 2001.

PMID- 12201391
TI  - Learning from Bristol: report of the public inquiry into children's heart surgery
      at Bristol Royal Infirmary 1984-1995.

PMID- 12201392
TI  - Shaken Baby Syndrome: fundamental questions.

PMID- 12201393
TI  - Biomechanics and neuropathology of adult and paediatric head injury.
AB  - The objective of this study was to understand the biomechanics in age-related
      primary traumatic brain injuries (TBI) causing initial severity and secondary
      progressive damage and to develop strategy reducing TBI outcome variability using
      biomechanical reconstruction to identify types of causal mechanisms prior to
      clinical trials of neuro-protective treatment. The methods included the
      explanation of TBI biomechanics and physiopathological mechanisms from dual
      perspectives of neurosurgery and biomechanical engineering. Scaling of tolerances
      for skull failure and brain injuries in infants, children and adults are
      developed. Diagnostic assumptions without biomechanical considerations are
      critiqued. Methods for retrospective TBI reconstruction for prevention are
      summarized. Mechanisms of TBI are based on the differences between the mechanical
      properties of the head and neck related to age. Skull fracture levels correlate
      with increasing cranial bone thickness and in the development of the cranial
      sutures in infants and in adults. Head injury tolerance levels at three age
      categories for cerebral concussion, skull fracture and three grades of diffuse
      axonal injuries (DAI) are presented. Brain mass correlates inversely for TBI
      caused by angular head motions and locations of injurious stresses are
      predictable by centripetal theory. Improved quantitative diagnosis of TBI type
      and severity levels depend primarily on age and biomechanical mechanisms.
      Reconstruction of the biomechanics is feasible and enables quantitative
      stratification of TBI severity. Experimental treatment has succeeded in
      preventing progressive damage in animal TBI models. In humans this has failed,
      because the animal model received biomechanically controlled TBI and humans did
      not. Clinical similarities of human TBI patients do not necessarily predict
      equivalent biomechanics because such trauma can be produced in various ways. We
      recommend 'reverse engineering' for in-depth reconstruction of the TBI injury
      mechanism for qualitative diagnoses and reduction of outcome variability.

PMID- 12201394
TI  - Auditing patient experience and satisfaction with neurosurgical care: results of
      a questionnaire survey.
AB  - The objective of this study was to determine the current level of patient
      satisfaction with neurosurgical services from the time of initial referral to
      hospital discharge. The survey was camed out by a self-administered postal
      questionnaire survey from the National Hospital for Neurology and Neurosurgery,
      London, UK. The participants were 364 patients discharged from the unit within
      one calendar year. The main outcome measures were level of satisfaction with
      various aspects of care, as measured by fixed response and free text style
      questions. Most patients are happy with the waiting time to see a neurosurgeon
      and the wait for subsequent admission acceptable, but many would have preferred
      it to be shorter. Twenty-seven had their original admission date cancelled, but
      most were happy with the explanation offered. Weaknesses in the management of
      outpatient clinics were highlighted, 35% of patients waiting more than half an
      hour to be seen. The great majority were happy with various aspects of
      communication with the neurosurgical team. Few patients were given the
      opportunity to follow up their visit with literature provided or a visit to a
      specialist nurse (17 and 9%, respectively). However, both were considered very
      useful, in particular, 93% highly valued a meeting with the specialist nurse.
      There was a dichotomy of opinion over the course of the inpatient stay. While
      most aspects of care received 70-80% satisfaction, the management of discharge
      received the most criticism. This was thought to represent a pooling of resources
      around the most needy patients. The majority of patients were discharged home
      (76%), only a third feeling that staff did everything possible to help this
      process. Very few received printed information. Again, those who had seen the
      specialty nurse had much higher levels of satisfaction. Patient satisfaction
      audit gives useful data on patients' perception and satisfaction with care that
      may not be apparent on more traditional audit measures such as length of stay,
      which focus more on a unit's efficiency. This study shows generally high levels
      of patient satisfaction with neurosurgical practice but highlights areas needing
      attention and expansion, such as access to a specialist nurse and relevant
      literature. Dissatisfaction with various administrative arrangements are clearly
      shown and provide an opportunity for patient centred improvements.

PMID- 12201395
TI  - Trauma to the pontomesencephalic brainstem-a major clue to the prognosis of
      severe traumatic brain injury.
AB  - The objective of this study was to assess the significance of an injury to the
      pontomesencephalic brainstem in severe traumatic brain injury [Glasgow coma score
      (GCS) below 8]. Forty victims of severe traumatic brain injury with and with out
      compounding pathologies almost equally distributed among both groups were
      studied. The outcome (mean follow-up, 11.3 months) was assessed by means of the
      Glasgow outcome score (GOS) and of the Disability rating scale (DRS). Injury of
      the brainstem was detected by electrophysiological investigation (evoked
      potentials, brainstem reflexes) and magnetic resonance imaging (MRI) carried out
      early after trauma. Statistical analysis (Wilcoxon signed rank test for matched
      pairs) revealed a significantly worse initial GCS (median 5 versus 6), GOS
      (median 3 versus 4), and DRS score (median 6 versus 2) for the group with
      brainstem lesions than for the group without such lesions. Moreover, there was a
      significant accumulation of lesions of the corpus callosum, the basal ganglia,
      and the (para-)hippocampal area detected by MRI in the brainstem lesion group. In
      addition, the finding of an abnormal cortical component of the median nerve
      evoked somatosensory potential was significantly more frequent in the patients
      with brainstem injury. Traumatic brainstem lesions diagnosed by MRI a nd/or
      electrophysiological investigation are associated with injury to other 'deeply'
      situated parts ofthe brain. The finding of a brainstem lesion influences to the
      outcome of patients after severe traumatic brain injury.

PMID- 12201396
TI  - A stereoscope for image-guided surgery.
AB  - A method of image guidance for neurosurgery using the surgeon's binocular depth
      perception is described. Magnetic resonance volume acquisitions and surface
      rendering software were used to produce stereoscopic pairs of images of the
      surface of the heads of patients with brain tumours. Stereoscopic pairs of the
      surface rendering of the tumour were also produced. The two pairs of images were
      colour-coded and combined into one pair of 35-mm slides. A stereoscopic viewer
      was constructed to allow simultaneous viewing of the pair of slides and the
      patient's head. Registration was achieved by moving the stereoscope in space
      until the virtual images of the rendered surface of the head coincided with the
      real head. The stereoscope was then locked in position and the virtual image of
      the tumour was projected 'into' the patient's head to allow the surgeon to locate
      the tumour. The instrument was used in six cases. A lateral accuracy of 10-15 mm
      was achieved and a depth accuracy of 5-10 mm.

PMID- 12201397
TI  - Phase I clinical trial on adjuvant active immunotherapy of human gliomas with GD2
      conjugate.
AB  - The objective of this study was to determine the feasibility, toxicity, and
      potential therapeutic benefits of an adjuvant active immunotherapy using a tumour
      specific ganglioside (GD2) conjugate for the adjuvant treatment of recurrent or
      progressive gliomas. Seven patients with proven GD2 expression in surgical
      specimens underwent a vaccination course with GD2-KLH/MPL-A conjugate. The follow
      up was performed according to WHO guidelines regarding common toxicity criteria.
      Antibody titres against the ganglioside and the adjuvants were analysed. All
      patients developed a local type 4 reaction. Anti-GD2-antibody titres could not be
      detected, despite high titres against the immunoadjuvants. No tumour regression
      was observed. The disease remained stable for a median of 21.5 weeks (6-34
      weeks). The median survival time after the first immunization was 47 weeks. The
      medial total survival time was 76 weeks. Adverse effects have not been observed.
      Active GD2-KLH/MPL-A immunization was technically feasible, but did not elicit
      anti-GD2 antibody generation.

PMID- 12201398
TI  - Posttraumatic syringomyelia: predisposing factors.
AB  - Posttraumatic spinal cord cavitation (syrinx) and progressive myelopathy
      associated with a posttraumatic syrinx (PTS) have been recognized for many years.
      Predisposing factors for PTS have not been well defined. All symptomatic PTS
      patients (n = 58) treated at the University of Toronto neurosurgical units over
      30 years were analysed retrospectively to discover risk factors for the
      development of PTS. There were 46 males and 12 females (mean age 42.2 years); 28
      patients had cervical (CSCI), and 30 had thoracic and lumbar spinal cord injuries
      (TSCI). Neurological deficit was complete in 40 (69%) compared with 43% complete
      injuries in the concurrent spinal and injury (SCI) population in general (p =
      0.0003). Onset of PTS was earlier with: increasing age (p < 0.02), cervical and
      thoracic levels of injury (p < 0.007 and p < 0.02, respectively, compared with
      lumbar injuries), dislocated fractures (p < 0.003) and spinal surgery (p < 0.001)
      and, marginally, with complete SCI (p = 0.06). Mean time to onset of PTS appears
      to have decreased in recent years (p < 0.0001). PTS follows complete spinal cord
      injury (SCI) more often than incomplete and is frequently associated with
      arachnoiditis. Onset is earlier with increasing age, cervical and thoracic levels
      compared with lumbar, displaced fractures and spinal instrumentation without
      decompression. A group of SCI patients who are at greater risk of developing
      early PTS is thus identified, facilitating cost-effective follow-up.

PMID- 12201399
TI  - Malignancy in a vestibular schwannoma. Report of a case with central
      neurofibromatosis, treated by both stereotactic radiosurgery and surgical
      excision, with a review of the literature.
AB  - Malignant change in schwannoma is rare. Malignant change in a vestibular
      schwannoma (acoustic neuroma) is even more rare. This paper presents a case of
      rapidly growing vestibular schwannoma first treated by radiosurgery whose
      histopathology after surgical excision 42 months later showed malignant changes.
      Up to now, eight cases of malignancy in eighth nerve tumours have been reported,
      four of which, including the present case, had previously been treated with
      radiosurgery and four cases that had not received radiation. Thus, it would seem,
      the overall incidence is extremely low. Nevertheless, extreme vigilance and
      careful reporting continues to be necessary.

PMID- 12201400
TI  - How safe is twistdrill craniostomy?
AB  - The incidence of haemorrhagic complications of intracranial pressure monitoring
      (ICPM) has previously been reported. However, in these studies, the techniques
      employed to access the inside of the cranium varied. While 3-mm essentially blind
      'twistdrill' craniostomies have been used, their role has been limited for fear
      of haemorrhagic sequelae. This has also restricted their use in clinical
      applications other than ICPM. We conducted a prospective observational study
      looking at haemorrhagic complications of the twistdrill in order to determine its
      safety and whether it has a role in other clinical settings. Over the period
      January 1994-February 2001, 941 patients had 1032 twistdrill procedures. There
      were 550 (58.4%) male patients and 391 (41.6%) female. The age range was 3 months
      to 93 years (median age 35 years). Only four procedures (0.38%) caused clinically
      significant bleeds attributable to the twistdrill --all of which were managed
      conservatively without requiring surgical evacuation. We conclude that twistdrill
      craniostomies are safe and that their use could be extended to other
      neurosurgical procedures and potentially to ICPM in non-neurosurgical centres.

PMID- 12201401
TI  - Acute extradural haematoma occurring during twistdrill craniostomy for chronic
      subdural haematoma.

PMID- 12201402
TI  - Schistosoma haematobium presenting as an intrinsic conus tumour.
AB  - In the small and diverse group of atypical, non-neoplastic intramedullary spinal
      cord lesions, parasitic infections are rarely considered, especially in Caucasian
      patients without systemic complaints or eosinophilia. A case of atypical
      myelopathy caused by Schistosoma haematobium is presented. The clinical,
      laboratory and imaging features in the MRI era both before and after treatment
      are discussed.

PMID- 12201403
TI  - Ring fracture of the skull base: case report and review of the literature.
AB  - Ring fractures of the skull base are rare and have hitherto been regarded as
      invariably fatal injuries. They are difficult to diagnose, as routine radiographs
      of the head and spine are usually normal. Increasing use of computerized
      tomography in the evaluation of head and neck injuries may, however, lead to an
      increased frequency of diagnosis of this injury. We present a case of such a
      fracture where the patient survived with a generally good neurological recovery.

PMID- 12201404
TI  - Colloid cysts of the third ventricle in identical twins.
AB  - A young man presented to our unit with a colloid cyst of the third ventricle.
      Following successful surgical treatment his parents expressed concern over the
      possibility of his identical twin brother having a similar cyst. After finding
      one other case of colloid cysts in identical twins in the world literature we
      arranged a magnetic resonance scan of the asymptomatic twin. We were sceptical,
      but much to our surprise the scan also showed a colloid cyst in the third
      ventricle. Familial colloid cysts of the third ventricle have been reported only
      rarely. This is the second account of third ventricular colloid cysts in
      identical twins reported in the world literature. We present case reports of the
      twins, discuss the world literature on familial colloid cysts and also the
      genetic implications.

PMID- 12201405
TI  - A subdural haematoma following 'reverse' bungee jumping.
AB  - Bungee jumping has been exploited commercially for 13 years and proprietors claim
      a good safety record. However, published case reports document a wide variety of
      possible injuries. To this list, we add a report of a subdural haematoma
      sustained during a variant of the sport, the 'reverse' bungee jump.

PMID- 12201406
TI  - Posterior femoral cutaneous nerve entrapment neuropathy: operative exposure and
      technique.
AB  - An isolated posterior femoral cutaneous nerve lesion is rare. There have been
      seven reported cases to date. We report a 51-year-old male with pain in the
      posterolateral thigh, atypical from the classic anatomical description.
      Somatosensory evoked potentials were suggestive of a posterior femoral cutaneous
      nerve lesion. We describe our operative exposure and technique for decompression
      of the posterior femoral cutaneous nerve and include a comparative anatomical
      explanation for the unusual area of our patient's pain.

PMID- 12201407
TI  - Application of the World Federation of Neurological Surgeons grading scale for
      subarachnoid haemorrhage with GCS 13-14.

PMID- 12201408
TI  - Diagnosis of neurocysticercosis.

PMID- 12201409
TI  - Effect of radiographic techniques (kVp and mAs) on image quality and patient
      doses in digital subtraction angiography.
AB  - We investigated how varying the x-ray tube voltage and image receptor input
      exposure affected image quality and patient radiation doses in interventional
      neuroradiologic imaging. Digital subtraction angiography (DSA) images were
      obtained of a phantom with 1 mm diameter vessels containing iodine at
      concentrations between 4.5 and 50 mg/cc. The detection threshold concentration of
      iodine was determined by inspecting DSA images obtained at a range of x-ray tube
      voltages and input exposure levels. Surface doses were obtained from measured x
      ray tube output data, and corresponding values of energy imparted were determined
      using the exposure-area product incident on the phantom. In one series of
      experiments, the air kerma at the image intensifier (X) was varied between 0.44
      microGy per frame and 8.8 microGy per frame at a constant x-ray tube voltage of
      70 kVp. In a second series of experiments, the tube voltage was varied between 50
      and 100 kVp, and the mAs adjusted to maintain a constant exposure level at the
      input of the image intensifier. At a constant x-ray tube voltage, the surface
      dose and energy imparted were directly proportional to the input exposure per
      frame used to acquire the DSA images. On our DSA system operated below 2.2
      microGy per frame, the threshold iodine concentration was found to be
      proportional to X(-0.57), which is in reasonable agreement with the theoretical
      prediction for a quantum noise limited imaging system. Above 2.2 microGy per
      frame, however, the threshold iodine concentration was proportional to X(-0.26),
      indicating that increasing the input exposure above this value will only achieve
      modest improvements in image quality. At a constant image intensifier input
      exposure level, increasing the x-ray tube voltage from 50 kVp to 100 kVp reduced
      the surface dose by a factor of 6.1, and the energy imparted by a factor of 3.5.
      The detection threshold iodine concentration was found to be proportional to
      kVp(n), where n was 2.1 at 1.1 microGy per frame, and 1.6 at 3.9 microGy per
      frame. For clinical situations that can be modeled by a uniform phantom, reducing
      the x-ray tube voltage rather than increasing the exposure level would best
      achieve improvements on our DSA imaging system performance.

PMID- 12201410
TI  - Material-specific analysis using coherent-scatter imaging.
AB  - Coherent-scatter computed tomography (CSCT) is a novel imaging method we are
      developing to produce cross-sectional images based on the low-angle (<10 degrees)
      scatter properties of tissue. At diagnostic energies, this scatter is primarily
      coherent with properties dependent upon the molecular structure of the scatterer.
      This facilitates the production of material-specific maps of each component in a
      conglomerate. Our particular goal is to obtain quantitative maps of bone-mineral
      content. A diagnostic x-ray source and image intensifier are used to acquire
      scatter patterns under first-generation CT geometry. An accurate measurement of
      the scatter patterns is necessary to correctly identify and quantify tissue
      composition. This requires corrections for exposure fluctuations, temporal lag in
      the intensifier, and self-attenuation within the specimen. The effect of lag is
      corrected using an approximate convolution method. Self-attenuation causes a
      cupping artifact in the CSCT images and is corrected using measurements of the
      transmitted primary beam. An accurate correction is required for reliable density
      measurements from material-specific images. The correction is shown to introduce
      negligible noise to the images and a theoretical expression for CSCT image SNR is
      confirmed by experiment. With these corrections, the scatter intensity is
      proportional to the number of scattering centers interrogated and quantitative
      measurements of each material (in g/cm3) are obtained. Results are demonstrated
      using both a series of poly(methyl methacrylate) (PMMA) sheets of increasing
      thickness (2-12 mm) and a series of 5 acrylic rods containing varying amounts of
      hydroxyapatite (0-0.400 g/cm3), simulating the physiological range of bone
      mineral density (BMD) found in trabecular bone. The excellent agreement between
      known and measured BMD demonstrates the viability of CSCT as a tool for
      densitometry.

PMID- 12201411
TI  - Pulsed-microwave-induced thermoacoustic tomography: filtered backprojection in a
      circular measurement configuration.
AB  - Our study on pulsed-microwave-induced thermoacoustic tomography in biological
      tissues is presented. A filtered backprojection algorithm based on rigorous
      theory is used to reconstruct the cross-sectional image from a thermoacoustic
      measurement in a circular configuration that encloses the sample under study.
      Specific details describing the measurement of thermoacoustic waves and the
      implementation of the reconstruction algorithm are discussed. A two-dimensional
      (2D) phantom sample with 2 mm features can be imaged faithfully. Through
      numerical simulation, the full width half-maximum (FWHM) of the point-spread
      function (PSF) is calculated to estimate the spatial resolution. The results
      demonstrate that the circular measurement configuration combined with the
      filtered backprojection method is a promising technique for detecting small
      tumors buried in biological tissues by utilizing microwave absorption contrast
      and ultrasound spatial resolution (approximately mm).

PMID- 12201412
TI  - Empirical description and Monte Carlo simulation of fast neutron pencil beams as
      basis of a treatment planning system.
AB  - The fast neutron beam, used for fast neutron therapy in Essen, is produced by the
      nuclear reaction of a 14 MeV cyclotron-based deuteron beam on a thick beryllium
      target. The resulting neutron beam has a continuous energy spectrum with a mean
      and a maximum energy equal to 5.5 and 18 MeV, respectively. The dose delivered to
      the patient is computed by a treatment planning system (TPS) based on an
      empirical model, in which the dose components (neutron and photon) are described
      by analytical functions. In order to improve the dose calculation, and thus to
      use the fast neutron beam for other applications (e.g., Boron Neutron Capture
      Enhancement of Fast Neutron Therapy), in this work we aim to develop a new TPS.
      For this purpose, a model based on pencil beams of mono-energetic neutrons has
      been created. The neutron energy ranged from 0.25 MeV up to 17.25 MeV by steps of
      0.5 MeV in order to cover the energy range of the Essen facility. The Monte Carlo
      method was then used to simulate the transport of neutrons within such pencil
      beams in a homogeneous water phantom. By using Monte Carlo techniques, it is
      possible to distinguish the energy deposition due to a primary collision in water
      to that due to scattered neutrons. The energy deposition due to pencil beams of
      2.224 MeV photons, coming from hydrogen neutron capture reaction in the phantom
      or in the collimator, was also determined. In order to complete this work, air
      filled cylinders have been introduced in the water phantom. It is shown that the
      resulting depth dose curves for primary neutrons can be easily derived using the
      homogeneous phantom, and that the description of the effect on scattered neutron
      dose distribution is more complex. In this work we demonstrate the relevance of
      Monte Carlo simulations of mono-energetic neutron pencil beams for purposes of
      neutron treatment planning. Some additional work is still required to describe a
      clinical situation (continuous energy neutron spectrum) as well as to
      experimentally validate the method described here.

PMID- 12201413
TI  - Dose characterization in the near-source region for two high dose rate
      brachytherapy sources.
AB  - High dose rate (HDR) 192Ir sources are currently used in intravascular
      brachytherapy (IVB) for the peripheral arterial system. This poses a demand on
      evaluating accurate dose parameters in the near-source region for such sources.
      The purpose of this work is to calculate the dose parameters for the old
      VariSource HDR 192Ir source and the new microSelectron HDR 192Ir source, using
      Monte Carlo electron and photon transport simulation. The two-dimensional (2D)
      dose rate distributions and the air kerma strengths for the two HDR sources were
      calculated by EGSnrc and EGS4 Monte Carlo codes. Based on these data, the dose
      parameters proposed in the AAPM TG-60 protocol were derived. The dose rate
      constants obtained are 13.119+/-0.028 cGy h(-1) U(-1) for the old VariSource
      source, and 22.751+/-0.031 cGy h(-1) U(-1) for the new microSelectron source at
      the reference point (r0 = 2 mm, theta = pi/2). The 2D dose rate distributions,
      the radial dose functions, and the anisotropy functions presented for the two
      sources cover radial distances ranging from 0.5 to 10 mm. In the near-source
      region on the transverse plane, the dose effects of the charged particle
      nonequilibrium and the beta-particle dose contribution were studied. It is found
      that at radial distances ranging from 0.5 to 2 mm, these effects increase the
      calculated dose rates by up to 29% for the old VariSource source, and by up to
      12% for the new microSelectron source, which, in turn, change values of the
      radial dose function and the anisotropy function. The present dose parameters,
      which account for the charged particle nonequilibrium and the beta particle
      contribution, may be used for accurate IVB dose calculation.

PMID- 12201414
TI  - Evaluation of Kodak EDR2 film for dose verification of intensity modulated
      radiation therapy delivered by a static multileaf collimator.
AB  - A new type of radiographic film, Kodak EDR2 film, was evaluated for dose
      verification of intensity modulated radiation therapy (IMRT) delivered by a
      static multileaf collimator (SMLC). A sensitometric curve of EDR2 film irradiated
      by a 6 MV x-ray beam was compared with that of Kodak X-OMAT V (XV) film. The
      effects of field size, depth and dose rate on the sensitometric curve were also
      studied. It is found that EDR2 film is much less sensitive than XV film. In high
      energy x-ray beams, the double hit process is the dominant mechanism that renders
      the grains on EDR2 films developable. As a result, in the dose range that is
      commonly used for film dosimetry for IMRT and conventional external beam therapy,
      the sensitometric curves of EDR2 films cannot be approximated as a linear
      function, OD = c * D. Within experimental uncertainty, the film sensitivity does
      not depend on the dose rate (50 vs 300 MU/min) or dose per pulse (from 1.0 x 10(
      4) to 4.21 x 10(-4) Gy/pulse). Field sizes and depths (up to field size of 10 x
      10 cm2 and depth = 10 cm) have little effect on the sensitometric curves. Percent
      depth doses (PDDs) for both 6 and 23 MV x rays were measured with both EDR2 and
      XV films and compared with ion chamber data. Film data are within 2.5% of the ion
      chamber results. Dose profiles measured with EDR2 film are consistent with those
      measured with an ion chamber. Examples of measured IMRT isodose distributions
      versus calculated isodoses are presented. We have used EDR2 films for
      verification of all IMRT patients treated by SMLC in our clinic. In most cases,
      with EDR2 film, actual clinical daily fraction doses can be used for verification
      of composite isodose distributions of SMLC-based IMRT.

PMID- 12201415
TI  - Output variation from an intensity modulating dynamic collimator.
AB  - Intensity modulated radiation therapy (IMRT) offers a method of delivering
      radiation dose conforming to the shape of targets while minimizing the dose to
      the surrounding tissue and nearby critical organs. One popular device is the
      NOMOS MIMiC Collimator coupled to the CORVUS treatment planning system. The MIMiC
      collimator, mounted on a linac head, opens and closes one or more of its 40 small
      leaves as determined by the planner while the linac delivers radiation and the
      gantry rotates. This dynamic IMRT allows the intensity to be modulated yielding a
      highly conformal dose distribution. However, the dose output becomes a function
      of the detailed manner in which the leaves open and close, since the opening and
      closing are not instantaneous. We investigate the effect of switch rates and
      delay in the open/close events on the output profiles. The output is enhanced as
      the switch rate increases. The enhancement factor at any point of measurement is
      dependent on its distance from the central plane. We interpret these variations
      in terms of a simple model, which includes the effect of leaf travel time during
      the process of opening and closing. We also include the time delay in
      establishing the specified pressure in the pneumonic device, which controls the
      opening and closing of the leaves. The information presented here offers a means
      for incorporating these output changes into the planning system. This may avoid
      the current situation where many patient plans need to be renormalized based on
      the actual measurement taken during the delivery of the specified intensity
      pattern to a phantom.

PMID- 12201416
TI  - Integration of digital fluoroscopy with CT-based radiation therapy planning of
      lung tumors.
AB  - Radiation dose escalation may be a means to increase the local control rate of
      inoperable lung tumors. Treatment plans involve the creation of a uniform
      planning target volume (PTV) to ensure proper coverage despite patient breathing
      and setup error. This may lead to unnecessary radiation of normal tissue in
      shallow breathers or target underdosing for patients with excess internal motion.
      Therefore, the nature of tumor motion for each patient should be measured in 3D,
      something that cannot be done with CT alone. We have developed a method that
      acquires 2D real-time fluoroscopic images (loops) and coregisters them with 2D
      digitally reconstructed radiographs (DRR) formed from the CT scan. The
      limitations of CT to encompass motion can be overcome by merging the two
      modalities together. The accuracy of the coregistration method is tested with a
      stationary grid of radio-opaque markers at various spatial positions. The in
      plane (at-depth) displacement between markers on the fluoroscopic image versus
      the DRR varies with position across the image due to slight misalignments between
      the x-ray source used in fluoroscopy and the virtual source used for the DRR
      relative to the test object. At clinically relevant positions, the maximum,
      measured in-plane displacement, is 1.1 mm. The method is applied to the thorax of
      an anthropomorphic phantom and a good fit is observed between the appearances of
      the bony anatomical structures on the coregistered image. Finally, a series of
      motion measurements are carried out on two oscillating cylindrical objects. The
      degree of motion as measured by fluoroscopy is accurate to within 1.0 mm, whereas
      the DRR is inconsistent in predicting motion. The coregistration of fluoroscopic
      loops with the DRR shows at what point within the oscillation the DRR fails to
      encompass motion. For any treatment site involving target motion, this real-time
      imaging is a useful asset in the planning stage.

PMID- 12201417
TI  - A preliminary comparative study of two treatment planning systems developed for
      boron neutron capture therapy: MacNCTPlan and SERA.
AB  - Two treatment planning systems have been specifically developed for BNCT:
      MacNCTPlan by the Harvard-MIT group and the SERA system developed by the
      INEEL/Montana State University group. In order to compare the dose components
      computed by the treatment planning systems, and therefore the clinical results
      available, it is important to first compare the basic features of the codes. This
      study investigated the effect of the reconstruction techniques and the form of
      the cross-section libraries used by the two treatment planning systems on the
      thermal neutron fluence distributions. Six mono-directional neutron sources of
      0.0253 eV, 1 keV, 5 keV, 10 keV, 100 keV, and 1 MeV were directed onto simple
      geometric phantoms filled with water. The general-purpose Monte Carlo radiation
      transport code MCNP was used as a reference tool in this study. For the examples
      studied, it is found that the methods used for geometry representation (in
      MacNCTPlan) and for cross-section representation (in SERA) were found to impact
      directly on the accuracy of the calculated results.

PMID- 12201418
TI  - Aliasing effects in digital images of line-pair phantoms.
AB  - Line-pair phantoms are commonly used for evaluating screen-film systems. When
      imaged digitally, aliasing effects give rise to additional periodic patterns.
      This paper examines one such effect that medical physicists are likely to
      encounter, and which can be used as an indicator of super-resolution.

PMID- 12201419
TI  - Peak velocity determination using fast Fourier velocity encoding with minimal
      spatial encoding.
AB  - For quantitative peak velocity determination, a technique was developed that uses
      Fourier velocity encoding (FVE) for the fast acquisition of images of velocity
      with no spatial encoding other than slice selection. The technique produces
      images of velocity versus temporal frequency. In applications where the quantity
      of interest is the peak velocity and in-plane spatial localization is not
      required, high SNR images are produced with reduced sensitivity to errors due to
      slice thickness and motion. The technique was validated using steady and
      pulsatile flow in a straight tube, and compared to both phase contrast
      measurements and numerical models using steady flow in a 50% and a 75%
      cosinusoidal stenosis phantom. Results show that for slices as large as 2 cm
      and/or undergoing periodic motion, FVE can accurately measure the peak velocity
      in cases where a distribution of velocities exist.

PMID- 12201420
TI  - Dosimetric characteristics of Novalis shaped beam surgery unit.
AB  - The dosimetric characteristics of a new dedicated radiosurgical treatment unit
      are systematically measured in terms of its percent depth dose, beam profile, and
      relative scatter factor. High-resolution diode detector, mini-ion-chamber
      detector, and conventional Kodak XV films are used to measure dosimetric data for
      a range of field sizes from 6x6 mm to 100x100 mm. The effects of collimator size,
      micro-multileaf collimator shape, and detector type on the dosimetric data are
      investigated. Results indicate that, with careful design, accurate dosimetric
      data could be acquired using either a dedicated diode detector or a mini-ion
      chamber detector, and film detector. Special attention is required when measuring
      dosimetric data for small field sizes such as 6x6 mm.

PMID- 12201421
TI  - A dual-energy subtraction technique for microcalcification imaging in digital
      mammography--a signal-to-noise analysis.
AB  - Breast cancer may manifest as microcalcifications (microCs) in x-ray mammography.
      However, the detection and visualization of microCs are often obscured by the
      overlapping tissue structures. The dual-energy subtraction imaging technique
      offers an alternative approach for imaging and visualizing microCs. With this
      technique, separate high- and low-energy images are acquired and their
      differences are used to "cancel" out the background tissue structures. However,
      the subtraction process could increase the statistical noise level relative to
      the calcification contrast. Therefore, a key issue with the dual-energy
      subtraction imaging technique is to weigh the benefit of removing the cluttered
      background tissue structure over the drawback of reduced signal-to-noise ratio in
      the subtracted microC images. In this report, a theoretical framework for
      calculating the (quantum) noise in the subtraction images is developed and the
      numerical computations are described. We estimate the noise levels in the dual
      energy subtraction signals under various imaging conditions, including the x-ray
      spectra, microC size, tissue composition, and breast thickness. The selection of
      imaging parameters is optimized to evaluate the feasibility of using a dual
      energy subtraction technique for the improved detection and visualization of
      microCs. We present the results and discuss its dependence on imaging parameters.

PMID- 12201422
TI  - A dosimetric comparison of two multileaf collimator designs.
AB  - We present the results of measurements designed to compare two different
      multileaf collimator (MLC) designs using a novel evaluation technique. The MLC
      designs evaluated were: a "single-focused" MLC (SF-MLC) mounted below the jaws,
      and a "double-focused" MLC, which is a complete replacement for the lower jaws.
      The ability of each MLC to conform isodose lines to a prescribed field edge (PFE)
      was evaluated using film dosimetry. Circular fields, centered on axis and off
      axis, were used because they produce a range of "angles of approach" between the
      MLC leaves and the PFE. They also have the advantage that for an ideal field
      shaping system the resulting isodoses are concentric perfect circles, a well
      defined basis for evaluation. The amplitude of the oscillations of the 50%
      isodose line about the PFE and the penumbra width as determined by the 20%, 80%,
      and 90% isodose lines was examined. We observe that the 50% isodose line
      oscillates around the PFE with greater amplitude for SF-MLC. We attribute this,
      at least in part, to the rounded ends of the SF-MLC leaves. However, the SF-MLC
      has a noticeably sharper penumbra, which we attribute to its position further
      from the source. We conclude that these results are relevant for accurate
      dosimetric modeling of these devices.

PMID- 12201423
TI  - Distortion correction for x-ray image intensifiers: local unwarping polynomials
      and RBF neural networks.
AB  - In this paper we present two novel techniques, namely a local unwarping
      polynomial (LUP) and a hierarchical radial basis function (HRBF) network, to
      correct geometric distortions in XRII images. The two techniques have been
      implemented and compared, in terms of residual error measured at control and
      intermediate points, with local and global methods reported in the previous
      literature. In particular, LUP rests on a locally optimized 3rd degree polynomial
      applied within each quadrilateral cell on the rectilinear calibration grid of
      points. HRBF, based on a feed-forward neural network paradigm, is constituted by
      a set of hierarchical layers at increasing cut-off frequency, each characterized
      by a set of Gaussian functions. Extensive experiments have been performed both on
      simulated and real data. In simulation, we tested the effect of pincushion,
      sigmoidal and local distortions, along with the number of calibration points.
      Provided that a sufficient number of cells of the calibration grid is available,
      the obtained accuracy for both LUP and HRBF is comparable to or better than that
      of global polynomial technique. Tests on real data, carried out by using two
      different (12 in. and 16 in.) XRIIs, showed that the global polynomial accuracy
      (0.16+/-0.08 pixels) is slightly worse than that of LUP (0.07+/-0.05 pixels) and
      HRBF (0.08+/-0.04 pixels). The effects of the discontinuity at the border of the
      local areas and the decreased accuracy at intermediate points, typical of local
      techniques, have been proved to be smoothed for both LUP and HRBF.

PMID- 12201424
TI  - Interinstitutional variations of sensitometric curves of radiographic dosimetric
      films.
AB  - Depth and field size dependence of the sensitometric curves of radiographic films
      have been studied by various groups. Limited information is, however, available
      on the magnitude of the variations in sensitometric curves applied in clinical
      practice in different institutions. In this study we assessed in a systematic way
      the effect of the various parameters influencing the shape of the sensitometric
      curve: batch composition, irradiation conditions, film processing, and film
      scanning. Two types of film, Kodak X-Omat V and CEA TVS, were irradiated,
      processed, and analyzed in three different institutions. The interinstitutional
      variation of the sensitometric curves, expressed as the OD variation at 50 cGy,
      can be up to 32% and is mainly caused by differences in film processing and to a
      lesser degree to differences in batch composition, film scanning, and irradiation
      conditions. For the Kodak films, the average OD difference at 50 cGy between the
      three institutions is 17% as a result of differences in batch composition and 25%
      due to differences in processing conditions. For the CEA films these data are 6%
      and 24%, respectively. The long-term variation of the sensitometric curves of
      KODAK films in one institution was smaller than the differences in batch
      composition between the three institutions. The sensitometric curves of CEA films
      showed in one institution a large variation with time; the shape gradually varied
      from sigmoidal to quasilinear. By using relative OD values rather than absolute
      OD values, variations in sensitometric curves of KODAK films can be reduced to
      2%. Consequently, one sensitometric curve is sufficient to derive relative dose
      values. If processing conditions are well controlled, it might therefore be
      advantageous to determine the absolute OD only at one or two dose values, in
      combination with a "universal" relative sensitometric curve.

PMID- 12201425
TI  - Commissioning and quality assurance of an optically guided three-dimensional
      ultrasound target localization system for radiotherapy.
AB  - Recently, there has been proliferation of image-guided positioning systems for
      high-precision radiation therapy, with little attention given to quality
      assurance procedures for such systems. To ensure accurate treatment delivery,
      errors in the imaging, localization, and treatment delivery processes must be
      systematically analyzed. This paper details acceptance tests for an optically
      guided three-dimensional (3D) ultrasound system used for patient localization.
      While all tests were performed using the same commercial system, the general
      philosophy and procedures are applicable to all systems utilizing image guidance.
      Determination of absolute localization accuracy requires a consistent
      stereotactic, or three-dimensional, coordinate system in the treatment planning
      system and the treatment vault. We established such a coordinate system using
      optical guidance. The accuracy of this system for localization of spherical
      targets imbedded in a phantom at depths ranging from 3 to 13 cm was determined to
      be (average +/- standard deviation) AP = 0.2 +/- 0.7 mm, Lat = 0.9 +/- 0.6 mm, Ax
      = 0.6 +/- 1.0 mm. In order to test the ability of the optically guided 3D
      ultrasound localization system to determine the magnitude of an internal organ
      shift with respect to the treatment isocenter, a phantom that closely mimics the
      typical human male pelvic anatomy was used. A CT scan of the phantom was
      acquired, and the regions of interest were contoured. With the phantom on the
      treatment couch, optical guidance was used to determine the positions of each
      organ to within imaging uncertainty, and to align the phantom so the plan and
      treatment machine coordinates coincided. To simulate a clinical misalignment of
      the treatment target, the phantom was then shifted by different precise offsets,
      and an experimenter blind to the offsets used ultrasound guidance to determine
      the magnitude of the shifts. On average, the magnitude of the shifts could be
      determined to within 1.0 mm along each axis.

PMID- 12201426
TI  - Spectral reconstruction of high energy photon beams for kernel based dose
      calculations.
AB  - A kernel-based dose computation method with finite-size pencil beams (FSPBs)
      requires knowledge of the photon spectrum. Published methods of indirect spectral
      measurements using transmission measurements through beam attenuators use
      mathematical fits with a large number of parameters and constraints. In this
      study, we examine a simple strategy for fitting transmission data that models
      important physical characteristics of photon beams produced in clinical linear
      accelerators. The shape of an unattenuated bremsstrahlung spectrum is known,
      varying linearly from a maximum at zero energy to a value of zero at a maximum
      energy. This unattenuated spectrum is altered primarily by absorption of low
      energy photons by the flattening filter, causing the true spectrum to roll off to
      zero at low photon energies. A fitting equation models this behavior and has
      these advantages over previous methods: (1) the equation describes the shape of a
      bremsstrahlung spectrum based on physical expectations; and (2) only three fit
      parameters are required with a single constraint. Results for 4 MV and 6 MV
      accelerators for central axis and off-axis beams show good agreement with the
      maximum, average and modal energies for known spectra. Previously published
      models, representations of beam fluence (energy fluence, dN/dE), experimental
      methods, and the fitting process are discussed.

PMID- 12201427
TI  - Using a tungsten rollbar to characterize the source spot of a megavoltage
      bremsstrahlung linac.
AB  - In photon teletherapy, the size and functional form of the photon source spot
      affect both the sharpness of the penumbra of treatment fields and the sharpness
      of portal images. Photon source spot parameters are also used in photon
      teletherapy dose calculation codes. A simple method for characterizing the source
      spot would complement the existing, more involved methods that have been
      described in the medical physics literature. Such a method, using a rollbar made
      of tungsten or other high-Z metal, is used in industrial radiography. We describe
      the use of a tungsten rollbar for characterizing the source spot edge spread
      function (and thereby the source spot size and shape) of a megavoltage
      bremsstrahlung photon source. We use Monte Carlo simulations to quantify
      anticipated experimental artifacts of the method, assuming typical spot sizes for
      circ-function, Gaussian, and Bennett line shapes. We illustrate the use of the
      rollbar method by characterizing the source spot of a typical 9 MV linac used for
      industrial radiography. The source spot is analyzed using two approaches: (a)
      fitting the rollbar image with analytic functions and (b) using Abel inversion to
      obtain the cylindrically symmetric spot profile consistent with the measured
      rollbar image. Monte Carlo simulations, based on a 6 MV photon teletherapy
      accelerator, suggest that aspects of the method are applicable to medical
      bremsstrahlung sources.

PMID- 12201428
TI  - A knowledge-based cone-beam x-ray CT algorithm for dynamic volumetric cardiac
      imaging.
AB  - With the introduction of spiral/helical multislice CT, medical x-ray CT began a
      transition into cone-beam geometry. The higher speed, thinner slice, and wider
      coverage with multislice/cone-beam CT indicate a great potential for dynamic
      volumetric imaging, with cardiac CT studies being the primary example. Existing
      ECG-gated cardiac CT algorithms have achieved encouraging results, but they do
      not utilize any time-varying anatomical information of the heart, and need major
      improvements to meet critical clinical needs. In this paper, we develop a
      knowledge-based spiral/helical multislice/cone-beam CT approach for dynamic
      volumetric cardiac imaging. This approach assumes the relationship between the
      cardiac status and the ECG signal, such as the volume of the left ventricle as a
      function of the cardiac phase. Our knowledge-based cardiac CT algorithm is
      evaluated in numerical simulation and patient studies. In the patient studies,
      the cardiac status is estimated initially from ECG data and subsequently refined
      with reconstructed images. Our results demonstrate significant image quality
      improvements in cardiac CT studies, giving clearly better clarity of the chamber
      boundaries and vascular structures. In conclusion, this approach seems promising
      for practical cardiac CT screening and diagnosis.

PMID- 12201429
TI  - Exploring the limits of spatial resolution in radiation dose delivery.
AB  - Flexibility and complexity in patient treatment due to advances in radiotherapy
      techniques necessitates a simple method for evaluating spatial resolution
      capabilities of the dose delivery device. Our purpose in this investigation is to
      evaluate a model that describes the ability of a radiation therapy device to
      deliver a desired dose distribution. The model is based on linear systems theory
      and is analogous to methods used to describe resolution degradation in imaging
      systems. A qualitative analysis of spatial resolution degradation using the model
      is presented in the spatial and spatial frequency domains. The ability of the
      model to predict the effects of geometric dose conformity to treatment volumes is
      evaluated by varying multileaf collimator leaf width and magnitude of dose
      spreading. Dose distributions for three clinical treatment shapes, circular
      shapes of varying diameter and one intensity modulated shape are used in the
      evaluation. We show that the model accurately predicts the dependence of dose
      conformity on these parameters. The spatial resolution capabilities of different
      radiation therapy devices can be quantified using the model, providing a simple
      method for comparing different treatment machine characteristics. Also, as
      different treatment sites have different resolution requirements this model may
      be used to tailor machine characteristics to the specific site.

PMID- 12201430
TI  - Effects of constant frequency noise in magnetic resonance imaging with nonuniform
      k-space sampling.
AB  - Magnetic resonance images can be compromised by constant frequency (CF) noise,
      such as radio frequency (RF) noise. We investigate the effects of CF noise in
      four imaging methods with non-uniform k-space sampling: single-shot echo-planar
      imaging (EPI) with sinusoidal readout gradients, phase-encoded echo-planar
      spectroscopic imaging (EPSI) with sinusoidal readout gradients, projection
      reconstruction imaging, and single-shot spiral imaging. The characteristics of
      the CF artifacts in each imaging method are studied with numerical simulations.
      CF noise is found to cause artifacts of nonclassic forms in the reconstructed
      images. Specifically, dashed-line, streak, and spiral patterns of CF noise appear
      in EPI/EPSI with sinusoidal readout gradients, projection-reconstruction imaging,
      and spiral imaging, respectively. The analytical expression for dashed-line
      artifacts is found to be a weighted sum of Bessel functions and is verified with
      in vivo experiments. The CF artifacts can be removed during post-processing by
      eliminating the noise spikes in the Fourier domain of the raw data.

PMID- 12201431
TI  - Comparison of three high-resolution digitizers for radiochromic film dosimetry.
AB  - A recently introduced radiographic film scanner from Howtek is evaluated and
      compared to two other commercially available densitometry systems for its use in
      radiochromic (RC) film dosimetry in the clinical dose range 0-100 Gy. It has a
      high-intensity red LED light-source centered at 662 nm (near the major absorption
      peak for RC film), and is coupled to a CCD linear array detector. This new
      densitometry system is directly compared to two high-resolution film scanners
      commonly employed in RC film dosimetry, namely the Lumiscan 75 digitizer (He-Ne
      laser light source) and the Vidar VXR-16 digitizer (fluorescent light source). A
      spot densitometer (Nuclear Associates Radiochromic Densitometer) with a filtered
      671 nm laser-diode light source is also included as a reference for comparison.
      The response of the spot densitometer and three high-resolution digitizers is
      characterized by the dose required to reach a net optical density of 1 (DNOD1),
      and is 16.0, 37.3, and 46.4 Gy for the Nuclear Associates Radiochromic
      Densitometer, Howtek MultiRAD 460 and Lumiscan 75 digitizer, respectively. The
      Vidar VXR-16 does not reach a net optical density of 1. The minimum usable dose
      at which a 2% level of uncertainty can be achieved (MUD2%) on the three
      digitizers are 2.6, 6.0, and 38.5 Gy for the Howtek MultiRAD 460, Lumiscan 75,
      and Vidar VXR-16, respectively. The Howtek MultiRAD 460 shows the greatest
      sensitivity, lowest MUD2% and best signal-to-noise ratio in the clinical dose
      range 0-100 Gy. Furthermore, it has no apparent interference (moire) artifacts
      that severely limit the low optical density region of the He-Ne laser digitizer.
      For high-resolution radiochromic dosimetry in the clinical dose range 0-100 Gy,
      the high-intensity red LED light-source digitizer proves to be the superior
      modality.

PMID- 12201432
TI  - IMRT verification by three-dimensional dose reconstruction from portal beam
      measurements.
AB  - A method of reconstructing three-dimensional, in vivo dose distributions
      delivered by intensity-modulated radiotherapy (IMRT) is presented. A proof-of
      principle experiment is described where an inverse-planned IMRT treatment is
      delivered to an anthropomorphic phantom. The exact position of the phantom at the
      time of treatment is measured by acquiring megavoltage CT data with the treatment
      beam and a research prototype, flat-panel, electronic portal imaging device.
      Immediately following CT imaging, the planned IMRT beams are delivered using the
      multiple-static field technique. The delivered fluence is sampled using the same
      detector as for the CT data. The signal measured by the portal imaging device is
      converted to primary fluence using an iterative phantom-scatter estimation
      technique. This primary fluence is back-projected through the previously acquired
      megavoltage CT model of the phantom, with inverse attenuation correction, to
      yield an input fluence map. The input fluence maps are used to calculate a
      "reconstructed" dose distribution using the same convolution/superposition
      algorithm as for the original planning dose calculation. Both relative and
      absolute dose reconstructions are shown. For the relative measurements,
      individual beam weights are taken from measurements but the total dose is
      normalized at the reference point. The absolute dose reconstructions do not use
      any dosimetric information from the original plan. Planned and reconstructed dose
      distributions are compared, with the reconstructed relative dose distribution
      also being compared to film measurements.

PMID- 12201433
TI  - Optimization of Ga-67 imaging for detection and estimation tasks: dependence of
      imaging performance on spectral acquisition parameters.
AB  - We have compared the use of two (93 and 185 keV) and three (93, 185, and 300 keV)
      photopeaks for Ga-67 tumor imaging and optimized the placement of each energy
      window. METHODS: The bases for optimization and evaluation were ideal and
      Bayesian signal-to-noise ratios (SNR) for the detection of spheres embedded in a
      realistic anthropomorphic digital torso phantom and ideal SNR for the estimation
      of their size and activity concentration. Seven spheres of radii ranging from 1
      to 3 cm, located at several sites in the torso, were simulated using a realistic
      Monte Carlo program. We also calculated the ideal SNR for the detection from
      simple phantom acquisitions. RESULTS: For detection and estimation tasks, the
      optimum windows were identical for all sphere sizes and locations. For the 93 keV
      photopeak, the optimal window was 84-102 keV for the detection and 87-102 keV for
      estimation; these windows are narrower than the 20% window often used in the
      clinic (83-101 keV). For the 185 keV photopeak, the optimal window was 170-220
      keV for the detection and 170-215 keV for estimation; these are substantially
      different than the 15% window used in our clinic (171-199 keV). For the 300 keV
      photopeak, the optimal window for detection was 270-320 keV, and for estimation,
      280-320 keV. Using the three optimized, rather than only the two lower-energy,
      windows yielded a 9% increase in the SNR for the detection of the 3 cm diam
      sphere (a 12% increase for a 2 cm diam sphere) and a 7% increase in the SNR for
      estimation of its size. For the acquired phantom data, detection also increased
      by 9%-12% when using three, rather than two, energy windows.

PMID- 12201434
TI  - A calibration approach to glandular tissue composition estimation in digital
      mammography.
AB  - The healthy breast is almost entirely composed of a mixture of fatty, epithelial,
      and stromal tissues which can be grouped into two distinctly attenuating tissue
      types: fatty and glandular. Further, the amount of glandular tissue is linked to
      breast cancer risk, so an objective quantitative analysis of glandular tissue can
      aid in risk estimation. Highnam and Brady have measured glandular tissue
      composition objectively. However, they argue that their work should only be used
      for "relative" tissue measurements unless a careful calibration has been
      performed. In this work, we perform such a "careful calibration" on a digital
      mammography system and use it to estimate breast tissue composition of patient
      breasts. We imaged 0%, 50%, and 100% glandular-equivalent phantoms of varying
      thicknesses for a number of clinically relevant x-ray techniques on a digital
      mammography system. From these images, we extracted mean signal and noise levels
      and computed calibration curves that can be used for quantitative tissue
      composition estimation. In this way, we calculate the percent glandular
      composition of a patient breast on a pixelwise basis. This tissue composition
      estimation method was applied to 23 digital mammograms. We estimated the
      quantitative impact of different error sources on the estimates of tissue
      composition. These error sources include compressed breast height estimation
      error, residual scattered radiation, quantum noise, and beam hardening. Errors in
      the compressed breast height estimate contribute the most error in tissue
      composition--on the order of +/-7% for a 4 cm compressed breast height: The
      spatially varying scattered radiation will contribute quantitatively less error
      overall, but may be significant in regions near the skinline. It is calculated
      that for a 4 cm compressed breast height, a residual scatter signal error is
      mitigated by approximately sixfold in the composition estimate. The error in
      composition due to the quantum noise, which is the limiting noise source in the
      system, is shown to be less than 1% glandular for most breasts.

PMID- 12201435
TI  - Numerical algorithms for spatial registration of line fiducials from cross
      sectional images.
AB  - We present several numerical algorithms for six-degree-of-freedom rigid-body
      registration of line fiducial objects to their marks in cross-sectional planar
      images, such as those obtained in CT and MRI, given the correspondence between
      the marks and line fiducials. The area of immediate application is frame-based
      stereotactic procedures, such as radiosurgery and functional neurosurgery. The
      algorithms are also suitable to problems where the fiducial pattern moves inside
      the imager, as is the case in robot-assisted image-guided surgical applications.
      We demonstrate the numerical methods on clinical CT images and computer-generated
      data and compare their performance in terms of robustness to missing data,
      robustness to noise, and speed. The methods show two unique strengths: (1) They
      provide reliable registration of incomplete fiducial patterns when up to two
      thirds of the total fiducials are missing from the image; and (2) they are
      applicable to an arbitrary combination of line fiducials without algorithmic
      modification. The average speed of the fastest algorithm is 0.3236 s for six
      fiducial lines in real CT data in a Matlab implementation.

PMID- 12201436
TI  - Practical aspects of functional MRI (NMR Task Group #8).
AB  - Functional MR imaging (fMRI) based upon the Blood Oxygen Level Dependent (BOLD)
      effect is currently an important new tool for understanding basic brain function
      and specifically allowing the correlation of physiological activity with
      anatomical location without the use of ionizing radiation. The clinical role of
      fMRI is still being defined and is the subject of much research activity. In this
      report we present the underlying physical, technical and mathematical principals
      of BOLD fMRI along with descriptions of typical applications. Our purpose in this
      report is to provide, in addition to basic principles, an insight into the
      aspects of BOLD imaging, which may be used by the medical physicist to assist in
      the implement of fMRI procedures in either a hospital or research environment.

PMID- 12201437
TI  - Medical physicists should assume PACS responsibilities.

PMID- 12201438
TI  - Parker weights revisited.

PMID- 12201439
TI  - Let's abandon geometry factors other than that of a point source in brachytherapy
      dosimetry.

PMID- 12201440
TI  - What is your diagnosis? Endoscopy demonstrated marked tracheal stenosis at the
      avulsed proximal tracheal segment.

PMID- 12201441
TI  - Treatment and therapeutic monitoring of canine hypothyroidism.
AB  - Thirty-one dogs with spontaneous hypothyroidism were treated with thyroid hormone
      replacement therapy (THRT) and monitored for approximately three months. Good
      clinical and laboratory control was ultimately achieved in all cases with a mean
      L-thyroxine (T4) dose of 0.026 mg/kg administered once daily. There was a
      significant increase and decrease in circulating total T4 and canine thyroid
      stimulating hormone (cTSH) concentrations, respectively, after starting THRT.
      After commencing treatment, 11 cases subsequently required an increase and three
      cases required a decrease in dose to achieve optimal clinical control. Median
      (semi interquartile range [SIR]) circulating six-hour post-pill total T4 (53.6
      [27.91 nmol/litre) and cTSH (0.03 [0] microg/litre) concentrations were
      significantly increased and decreased, respectively, in treated dogs that did not
      require a dose change; corresponding values in treated dogs in which an increase
      in dose was required were 29.3 (12.7) nmol/litre and 0.15 (0.62) microg/litre,
      respectively. However, circulating cTSH measurement was of limited value in
      assessing therapeutic control because, although increased values were associated
      with inadequate therapy, reference range cTSH values were common in inadequately
      treated dogs. Lethargy and mental demeanour were typically the first clinical
      signs to improve, with significant bodyweight reduction occurring within two
      weeks of commencing THRT. Routine clinicopathological monitoring was of value in
      confirming a general metabolic response to THRT, but was of limited value in
      accurately monitoring cases or tailoring therapy in individual cases.

PMID- 12201442
TI  - Transposition of the sacrotuberous ligament for the treatment of coxofemoral
      luxation in dogs.
AB  - A surgical technique is described for transposition of the sacrotuberous ligament
      to replace the teres ligament in the treatment of coxofemoral luxation in dogs.
      Ten dogs with coxofemoral luxation were treated using this technique and all
      animals regained full limb function within two months of surgery. It is suggested
      that the technique could be employed in dogs suffering from all types of hip
      luxations.

PMID- 12201443
TI  - Cellophane banding of congenital intrahepatic portosystemic shunts in two Irish
      wolfhounds.
AB  - Two three-month-old, male Irish wolfhound siblings were diagnosed with breed
      typical left divisional congenital intrahepatic portosystemic shunts consistent
      with patent ductus venosus. The shunts were amenable to surgical dissection at a
      posthepatic location. Both dogs had cellophane banding for shunt attenuation. One
      dog was euthanased after developing post-ligation neurological dysfunction, which
      was refractory to treatment. The other dog survived and demonstrated shunt
      attenuation. Successful surgical management using cellophane banding of a patent
      ductus venosus has not been previously described in a large-breed dog.

PMID- 12201444
TI  - Ulcerative otitis externa responsive to immunosuppressive therapy in two dogs.
AB  - Two middle-aged dogs were presented with bilateral severe ulcerative otitis
      externa without previous history of disease or evidence of other skin disease.
      Based on the exclusion of microbial infection and other primary causes,
      histopathological findings and response to immunomodulatory treatment, a
      diagnosis of presumed immune-mediated ulcerative otitis externa was made in both
      cases. However, the two cases differed with regard to their histopathological
      characteristics and the course of the disease. This report indicates that primary
      ulcerative disease needs to be considered in cases of ulcerative otitis externa
      which are unresponsive to appropriate antimicrobial therapy.

PMID- 12201445
TI  - Spontaneous hepatic rupture in six cats with systemic amyloidosis.
AB  - Spontaneous hepatic rupture, secondary to the accumulation of hepatic amyloid,
      was diagnosed in six cats over a two-year period. Previous reports of feline
      hepatic amyloidosis have documented clusters of cases from breeding catteries.
      Most affected cats have been Siamese or a related breed and the disease is
      generally regarded as familial. In contrast, the cases presented here were
      sporadic, with relatives and other cats in the household not clinically affected.
      They included a Devon rex, a breed not previously reported with this condition,
      and a domestic shorthair. Clinical signs in three of these cases had, prior to
      referral, been misinterpreted as resulting from blunt trauma, immune-mediated
      haemolysis or a coagulopathy. Antemortem diagnostic features, including new data
      on the value of hepatic ultrasonography and fine-needle aspirate cytology, are
      reported. These cases illustrate how the course of this disease can vary between
      individuals and that, despite the dramatic underlying pathology, hepatic
      amyloidosis can present a diagnostic challenge and should be suspected in any
      young adult cat with consistent clinical signs, irrespective of breed or
      environment.

PMID- 12201446
TI  - Oestrogen-induced bone marrow aplasia in a dog with a Sertoli cell tumour.
AB  - A 10-year-old male Drahthaar dog with unilateral cryptorchidism was examined
      because of feminisation and myelotoxicity. Radiography and ultrasonography
      revealed an abdominal mass which was surgically removed. The mass was identified
      as a Sertoli cell tumour on histological examination. Findings on bone marrow
      examination were compatible with aplasia due to the oestrogens secreted by the
      tumoral cells. Treatment with fluids, antibiotics, whole blood transfusions,
      corticosteroids and lithium carbonate was unsuccessful. Survival time was 22 days
      after surgery.

PMID- 12201447
TI  - Frank Beattie Travel Scholarship. Counselling in the veterinary arena.

PMID- 12201448
TI  - Pharmacy and dispensing courses: a new era.

PMID- 12201450
TI  - Quantitative 3-d diagnostic ultrasound imaging using a modified transducer array
      and an automated image tracking technique.
AB  - An approach for acquiring dimensionally accurate three-dimensional (3-D)
      ultrasound data from multiple 2-D image planes is presented. This is based on the
      use of a modified linear-phased array comprising a central imaging array that
      acquires multiple, essentially parallel, 2-D slices as the transducer is
      translated over the tissue of interest. Small, perpendicularly oriented, tracking
      arrays are integrally mounted on each end of the imaging transducer. As the
      transducer is translated in an elevational direction with respect to the central
      imaging array, the images obtained by the tracking arrays remain largely
      coplanar. The motion between successive tracking images is determined using a
      minimum sum of absolute difference (MSAD) image matching technique with subpixel
      matching resolution. An initial phantom scanning-based test of a prototype 8 MHz
      array indicates that linear dimensional accuracy of 4.6% (2 sigma) is achievable.
      This result compares favorably with those obtained using an assumed average
      velocity [31.5% (2 sigma) accuracy] and using an approach based on measuring
      image-to-image decorrelation [8.4% (2 sigma) accuracy]. The prototype array and
      imaging system were also tested in a clinical environment, and early results
      suggest that the approach has the potential to enable a low cost, rapid,
      screening method for detecting carotid artery stenosis. The average time for
      performing a screening test for carotid stenosis was reduced from an average of
      45 minutes using 2-D duplex Doppler to 12 minutes using the new 3-D scanning
      approach.

PMID- 12201451
TI  - Spatial resolution enhancement of ultrasound images using neural networks.
AB  - Spatial resolution in modern ultrasound imaging systems is limited by the high
      cost of large aperture transducer arrays, which require a large number of
      transducer elements and electronic channels. A new technique to enhance the
      spatial resolution of pulse-echo imaging systems is presented. The method
      attempts to build an image that could be obtained with a transducer array
      aperture larger than that physically available. We consider two images of the
      same object obtained with two different apertures, the full aperture and a
      subaperture, of the same transducer. A suitable artificial neural network (ANN)
      is trained to reproduce the relationship between the image obtained with the
      transducer full aperture and the image obtained with a subaperture. The inputs of
      the neural network are portions of the image obtained with the subaperture (low
      resolution image), and the target outputs are the corresponding portions of the
      image produced by the full aperture (high resolution image). After the network is
      trained, it can produce images with almost the same resolution of the full
      aperture transducer, but using a reduced number of real transducer elements. All
      computations are carried out on envelope-detected decimated images; for this
      reason, the computational cost is low and the method is suitable for real-time
      applications. The proposed method was applied to experimental data obtained with
      the ultrasound synthetic aperture focusing technique (SAFT), giving quite
      promising results. Real-time implementation on a modern, full-digital echographic
      system is currently being developed.

PMID- 12201453
TI  - Shift-invariant, DWT-based "projection" method for estimation of ultrasound pulse
      power spectrum.
AB  - An approach to computing estimates of the ultrasound pulse spectrum from echo
      ultrasound RF sequences, measured from biological tissues, is proposed. It is
      computed by a "projection" algorithm based on the Discrete Wavelet Transform
      (DWT) using averaging over a range of linear shifts. It is shown that the robust,
      shift invariant estimate of the ultrasound pulse power spectrum can be obtained
      by the projection of RF line log spectrum on an appropriately chosen subspace of
      L2(R) (i.e., the space of square-integrable functions) that is spanned by a
      redundant collection of compactly supported, scaling functions. This redundant
      set is formed from the traditional (in Wavelet analysis) orthogonal set of
      scaling functions and also by all its linear (discrete) shifts. A proof is given
      that the estimate, so obtained, could be viewed as the average of the orthogonal
      projections of the RF line log spectrum, computed for all significant linear
      shifts of the RF line log spectrum in frequency domain. It implies that the
      estimate is shift-invariant. A computationally efficient scheme is presented for
      calculating the estimate. Proof is given that the averaged, shift-invariant
      estimate can be obtained simply by a convolution with a kernel, which can be
      viewed as the discretized auto-correlation function of the scaling function,
      appropriate to the particular subspace being considered. It implies that the
      computational burden is at most O(n log2 n), where n is the problem size, making
      the estimate quite suitable for real-time processing. Because of the property of
      the wavelet transform to suppress polynomials of orders lower than the number of
      the vanishing moments of the wavelet used, the presented approach can be
      considered as a local polynomial fitting. This locality plays a crucial role in
      the performance of the algorithm, improving the robustness of the estimation.
      Moreover, it is shown that the "averaging" nature of the proposed estimation
      allows using (relatively) poorly regular wavelets (i.e., short filters), without
      affecting the estimation quality. The latter is of importance whenever the number
      of calculations is crucial.

PMID- 12201454
TI  - Sparse 2-D arrays for 3-D phased array imaging--design methods.
AB  - One of the most promising techniques for limiting complexity for real-time 3-D
      ultrasound systems is to use sparse 2-D layouts. For a given number of channels,
      optimization of performance is desirable to ensure high quality volume images. To
      find optimal layouts, several approaches have been followed with varying success.
      The most promising designs proposed are Vernier arrays, but also these suffer
      from high peaks in the sidelobe region compared with a dense array. In this work,
      we propose new methods based on the principles of suppression of grating lobes to
      form symmetric and non-symmetric regular sparse periodic and radially periodic
      designs. The proposed methods extend the concept of sparse periodic layouts by
      exploiting either an increased number of symmetry axes or radial symmetry. We
      also introduce two new strategies to form designs with non-overlapping elements.
      The performance of the new layouts range from the performance of Vernier arrays
      to almost that of dense arrays. Our designs have simplicity in construction,
      flexibility in the number of active elements, and the possibility of trade off
      sidelobe peaks against sidelobe energy.

PMID- 12201455
TI  - Sparse 2-d arrays for 3-D phased array imaging--experimental validation.
AB  - To be able to describe more precisely the behavior of a real-time 3-D ultrasound
      system with either a dense array or various sparse designs, experimental data
      from a 2-D fully connected array prototype with 50 x 50 elements have been
      collected. The data have been processed off line to form synthetic aperture 3-D
      volume images. Simulated and experimental results are compared and show good
      correlation. The performance of the best sparse designs, all thinned to more than
      50%, offer performances comparable to a dense array.

PMID- 12201456
TI  - Diagnostic ultrasound-induced membrane damage in phagocytic cells loaded with
      contrast agent and its relation to Doppler-mode images.
AB  - Cell membrane damage induced by diagnostic ultrasound exposure with contrast
      agent was examined and related to the display of stimulated acoustical emission
      in Doppler images. Monolayers of mouse macrophage-like cells were cultured on the
      inside of one window of an exposure chamber. The monolayers were incubated with
      5% Optison (Mallinckrodt, Inc., St. Louis, MO) for 15 minutes then rinsed to
      remove unattached gas bodies. A Spectra Plus scanner (Diasonics GE Medical
      Systems, Inc., Cincinnati, OH) in B-scan or Doppler-imaging modes exposed the
      chamber 3.5 cm away in a 37 degrees C water bath. The cells were scored either
      for uptake of fluorescent Dextran (sonoporation), or for trypan blue dye
      exclusion (cell death). No significant effect was seen for exposure in any mode
      without a contrast agent. Significant effects with contrast agent included 5.8%
      (2.3% standard deviation, SD) fluorescent cells and 33.4% (7.7% SD) trypan blue
      stained cells in Doppler-imaging modes, compared to 0.0% and 2.2% (1.7% SD),
      respectively, in sham exposures. Frames of the power Doppler image were analyzed
      for pixel brightness to quantify the brief flash in the Doppler window. Although
      both membrane damage and the flash brightness increased with increasing pressure
      amplitude, there did not appear to be a direct correlation between the two
      phenomena.

PMID- 12201465
TI  - Salvaging the indwelling central venous line: a technical note.

PMID- 12201466
TI  - Perioperative transfusion management.

PMID- 12201467
TI  - Decision making in perioperative transfusion.
AB  - Clinical decision making in transfusion medicine has received greater attention
      in recent years driven by concern about the potential hazards, especially since
      the recognition that HIV can be transmitted by homologous blood transfusion.
      These concerns about the risks of homologous transfusion has precipitated
      interest in the appropriateness of many transfusions and in the decision making
      processes in transfusion medicine. There has been increasing expenditure on the
      blood supply side to address the real or perceived potential infectious hazards.
      This has at times been to the detriment of the patient demand side of the
      homologous donor blood chain. This imbalance is now being addressed with the
      development of evidence based clinical guidelines for individual blood
      components, transfusion monitoring systems and quality assurance programmes. In
      this review of the process of clinical decision making in transfusion medicine
      and the factors involved in the ensuring a patient receives a safe and effect
      transfusion are addressed. The responsibilities of the patient's clinical carers
      are emphasised.

PMID- 12201468
TI  - The theory and practice of bloodless surgery.
AB  - The application of blood conservation strategies to minimise or avoid allogeneic
      blood transfusion is seen internationally as a desirable objective. Bloodless
      surgery is a relatively new practice that facilitates that goal. However, the
      concept is either poorly understood or evokes negative connotations. Bloodless
      surgery is a term that has evolved in the medical literature to refer to a peri
      operative team approach to avoid allogeneic transfusion and improve patient
      outcomes. Starting as an advocacy in the early 1960s, it has now grown into a
      serious practice being embraced by internationally respected clinicians and
      institutions. Central to its success is a coordinated multidisciplinary approach.
      It encompasses the peri-operative period with surgeons, anaesthetists,
      haematologists, intensivists, pathologists, transfusion specialists, pharmacists,
      technicians, and operating room and ward nurses utilising combinations of the
      numerous blood conservation techniques and transfusion alternatives now
      available. A comprehensive monograph on the subject of bloodless surgery along
      with detailed coverage of risks and benefits of each modality (some modalities
      are discussed in more detail elsewhere in this issue) is beyond the scope of this
      article. Accordingly, a brief overview of the history, theory and practice of
      bloodless surgery is presented, along with the clinical and institutional
      management requirements.

PMID- 12201469
TI  - Transplantation-associated thrombotic microangiopathy is associated with
      transplantation from unrelated donors, acute graft-versus-host disease and
      venoocclusive disease of the liver.
AB  - Transplantation-associated thrombotic microangiopathy (TA-TMA) has been
      associated with significantly reduced survival following allogeneic bone marrow
      transplantation. In this study we describe the course and response to plasma
      exchange therapy of TA-TMA as well as risk factors for its' development. Twenty
      five patients who underwent plasma exchange therapy were matched to fifty control
      patients selected for transplant indication and stage of disease at the time of
      transplant. Transplant indications were acute myeloid leukemia, acute
      lymphoblastic leukemia, chronic myeloid leukemia, aplastic anemia,
      myelodysplastic syndrome and multiple myeloma. Groups were well balanced with
      respect to disease status, age at time of transplant and use of radiation-based
      conditioning. TA-TMA was diagnosed a median of 27 days after transplantation and
      neurological abnormalities were present in ten cases. Patients received a median
      of 10 (range 2-43) plasma exchange treatments. Hematological responses were
      recorded in eight cases. Risk factors for the development of TA-TMA included
      transplantation from unrelated donors (p = 0.002), hepatic venoocclusive disease
      (VOD) (p = 0.034), grade 2-4 acute graft-versus-host disease (GVHD) (p = 0.042)
      and bacteremia with diphtheroid organisms (p = 0.009). Only hepatic VOD (p =
      0.0026) and grade 2-4 acute GVHD (p = 0.0436) remained significant risk factors
      for later development of TA-TMA in a multivariate logistic regression model. The
      median survival of patients with TA-TMA was 66 (range 32-733) days while that of
      unaffected patients was 742 (range 15-2392) days after transplantation. Only one
      patient with TA-TMA remains alive 733 days after transplantation.

PMID- 12201470
TI  - Pre-operative hemostatic assessment and management.
AB  - Excessive surgical bleeding can be predicted and then prevented in most patients
      with a recognised hereditary bleeding tendency or in those on anti-thrombotic
      therapy. However the clinical consultation of an individual patient can be
      challenging because the diagnosis can be unclear or a balance needs to be
      achieved between minimising bleeding without precipitating thrombosis. Laboratory
      testing does provide assistance in assessment of a bleeding tendency but it is
      not uncommon for the results to be inconclusive. Investigations such as the level
      of von Willebrand factor assays should be regarded as a continuous risk factor
      for surgical bleeding rather than defining a disease category. Appropriate
      replacement therapy prior to surgery is effective in preventing surgical
      bleeding. Aggressive anti coagulant therapy around the time of surgery in
      patients who usually are on warfarin more often lead to unnecessary haemorrhage
      rather than preventing further thrombosis. A risk assessment of both bleeding
      versus thrombosis for the particular operation is necessary to ensure the best
      outcome.

PMID- 12201471
TI  - Minimising intra-operative blood loss.
AB  - Minimising intra-operative blood loss involves using many different approaches to
      the problem (Fig. 1), all of which have application for particular types of
      surgery. There is however a need for careful cooperation between haemotologist,
      surgeon and anaesthetist to ensure that this important goal is achieved.

PMID- 12201472
TI  - Perioperative hemodilution.
AB  - Acute normovolemic hemodilution (ANH) entails the removal of blood from a patient
      either immediately before or shortly after induction of anesthesia and the
      simultaneous replacement with cell-free fluid, preferably synthetic colloids with
      a predictable volume effect (6% dextran 60/70, 6% hydroxyethyl starch 200,000 and
      130.000, respectively). Hemodilution is part of the concept for avoiding or
      limiting the use of allogeneic blood and should be considered for patients
      undergoing elective surgery free of contraindications and presenting with an
      initial hemoglobin concentration > or = 12 g/dl and an anticipated blood loss of
      > or = 1500 ml. The efficacy of ANH, judged by the necessity to transfuse
      homologous blood, depends on the preoperative (initial) hematocrit, the target
      hematocrit (to which hemodilution is performed), and the preset intra- and
      postoperative transfusion trigger. In the past data from clinical trials have
      shown that in healthy subjects a target hematocrit of 20-25% (7.0-8.0 g/dl
      hemoglobin concentration) is feasible and safe for the patient. The lower the
      target hemoglobin concentration, the more extensive monitoring is required:
      intraoperative target hemoglobin concentrations of 5.0 g/dl and less have been
      tolerated by young surgical patients without adverse effects. The safety as well
      as efficacy of acute normovolemic hemodilution in terms of reducing homologous
      blood transfusion requirements have been demonstrated in various clinical
      studies. ANH therefore is regarded an integral part of programs aimed at reducing
      the need for homologous blood, and can thus be successfully combined with
      preoperative autologous blood deposition, intraoperative blood salvage and
      carefully adjusted surgical techniques.

PMID- 12201473
TI  - Intra-operative autologous blood management.
AB  - The evolution of cardiac surgery has been accompanied by a wide variety of
      techniques and equipment available for blood conservation. It has also given us
      data that allows identification of preoperative risk factors for transfusion
      needs in other surgical specialties. There is however great diversity of opinion
      as to how this technology should be applied. Examples can be found in the
      literature of discrepancies between countries but also individual institutions .
      The authors encounter differences in opinion between practitioners regularly. The
      authors believe that the variance in opinion may be based on the experiences of
      single techniques and that a broader depth of practice is required to achieve
      best practices for intra-operative transfusion management. The most performed
      procedure in our experience is red cell salvage and processing with a cell
      washing device (CS). There are two primary issues related to CS, cost and
      reduction in allogenic blood exposure. A recent meta-analysis has shown that cell
      salvage in orthopedic surgery decreases the proportion of patients requiring
      allogeneic blood transfusion peri-operatively, but post-operative cell salvage is
      only marginally effective in cardiac surgery. There are close analogies to be
      drawn from issues surrounding the whole picture of transfusion. Medical practice
      guidelines are frequently promoted as a way to improve the cost-effectiveness of
      healthcare. But non-compliance with guidelines is still a major issue. Guiding
      the decision to transfuse or autotransfuse can improve transfusion practices, but
      effective processes must first identify problem(s) in transfusion practice and
      then include the attending medical practitioner as an educational target. Process
      improvements that have been shown to be effective include, briefly meeting one-on
      one with physicians, teaching at scheduled conferences, making daily clinical
      rounds of patients who receive transfusion, concurrently reviewing orders for
      transfusion before issue of the blood product, and installing algorithms and
      guidelines in the operating room. Transfusion practices improved with these
      process improvements. The success of a change of practice patterns relies on
      hospital administration, education and feedback, written and immediately
      available guidelines, employment of specially trained personnel, and establishing
      long-standing actions. It is the authors' observation that the success of an
      intra-operation blood management program is twofold, early identification of
      patients and a multi-team approach of Surgeon, Haematologist, Transfusion
      services, Anaesthetist and Perfusionist. This team approach offers far greater
      depth for management of intra-operative blood conservation and transfusion
      practice. Interventions must be patient specific and targeted toward the best
      possible patients outcome.

PMID- 12201474
TI  - Massive blood transfusion in the elective surgical setting.
AB  - Massive haemorrhage in elective surgery can be either anticipated (e.g. organ
      transplantation) or unexpected. Management requires early recognition, securing
      haemostasis and maintenance of normovolaemia. Transfusion management involves the
      transfusion of packed red cells, platelet concentrates and plasma (fresh frozen
      plasma and cryoprecipitate). Blood product support should be based on clinical
      judgment and be guided by repeated laboratory tests of coagulation. Although
      coagulation tests may not provide a true representation of in vivo haemostasis,
      they do assist in management of haemostatic factors. Below critical levels
      (prothrombin time or activated partial thromboplastin time >1.8; fibrinogen <1.0
      g/l; platelet count < 80 x 10(9) 1(-1)) it is difficult to achieve haemostasis.
      Despite seemingly adequate blood component therapy there remain situations where
      haemorrhage is uncontrollable. In this setting, alternative approaches must be
      considered. These include the use of other blood products (e.g. prothrombin
      complex concentrates; fresh whole blood; fibrin glue) and pharmacological agents
      (e.g. aprotinin). Complications of massive transfusion result in significant
      morbidity and mortality. These may be secondary to the storage lesion of the
      transfused blood products, disseminated intravascular coagulation, hypothermia or
      hypovolaemic shock. The use of fresh blood products and leucocyte-reduced packed
      red cells and platelets, may minimise some of the adverse clinical sequelae.

PMID- 12201475
TI  - Fast gas chromatography analysis of N-carbamates with cold on-column injection.
AB  - Direct gas chromatographic (GC) analysis of thermally labile N-carbamates is
      studied by using fast GC with cold on-column injection. With the greatly reduced
      injection temperature, short column lengths, high flow rate, and fast temperature
      programming rate, the exposure of carbamates to high temperature is reduced and
      degradation can be avoided. Nine N-carbamates in EPA Method 531 are eluted
      without thermal decomposition. The relative standard deviation percentage for
      peak areas average 1.9% for all of the carbamates analyzed. A conventional GC
      instrument is employed to simplify the experiments. GC-mass spectrometry is used
      to monitor the decomposition peaks.

PMID- 12201476
TI  - Simplified high-performance liquid chromatographic determination of residual
      amprolium in edible chicken tissues.
AB  - A simplified determining method for the routine monitoring of residual amprolium
      in edible chicken tissues (muscle and liver) is developed using a high
      performance liquid chromatographic (HPLC) method with a photodiode-array detector
      after sample cleanup by an Ultrafree-MC/PL centrifugal ultrafiltration unit. For
      the HPLC determination and identification, a Mightysil RP-4 GP column and a
      mobile phase of an ethanol-5 mM 1-heptanesulfonic acid sodium salt solution
      (35:65, v/v) using an ion-pairing system with a photodiode-array detector are
      used. Average recoveries (spiked at 0.3-3.0 microg/g) are > 90%. The inter- and
      intravariabilities are 1.9-2.4%. The limits of quantitation are 0.22 microg/g for
      muscle and 0.25 microg/g for liver. The total time and solvent required for the
      analysis of one sample are < 20 min and < 2 mL of ethanol, respectively. No toxic
      solvents and regents are used.

PMID- 12201477
TI  - Comparison of reversed-phase liquid chromatographic methods for the separation of
      new quinolones.
AB  - Reversed-phase high-performance liquid chromatography is widely used in the
      analysis of drug substances and their metabolites. The interaction of quinolones
      with residual silanol in a silica-based C18 stationary phase causes peak
      broadening and bad peak shapes and makes it hard to resolve the peak separations.
      This unusual interaction is studied and finally can be removed by masking the
      residual silanol of a silica-based C18 stationary phase, then good peak
      separation is achieved. We have chosen four new quinolones and ciprofloxacin and
      improved the peak shapes by optimizing the pH of the eluent and the quantity of
      the additive (N,N-dimethyloctylamine, approximately 0-40 mM) in the monomeric C18
      stationary phase. The elution behavior of quinolones in the polymeric C18
      stationary phase is compared with that in the monomeric C18 stationary phase
      under the same eluent condition. Good peak symmetry and a high plate number are
      achieved by this technique, which are hardly obtained with the conventional
      silica-based C18 stationary phase. Based on these results, we present data of the
      influence of the eluent composition such as pH, buffer, and additive
      concentration on the peak shape.

PMID- 12201478
TI  - A reactive analytical approach for the estimation of olefinic content in gasoline
      range hydrocarbons by gas chromatography.
AB  - The estimation of olefinic content in conversion processes such as the
      etherification of olefins in fluid catalytic cracking (FCC) gasoline is
      essentially required. Gas chromatography (GC) is the well-established method for
      the quantitative analysis of olefins in etherification processes. The current
      state-of-the-art GC methods employing highly specific long single capillary
      columns such as Petrocol-DH are being used for the analysis of gasoline-range
      hydrocarbons. However, the method needs many standard reference samples of
      respective components in a complex mixture of hydrocarbons, which limits the
      scope of the analytical method. The alternative approach followed by this
      investigation is based on the reactive method of the analysis of olefins in FCC
      light gasoline by subjecting them to hydrogenation and estimating the olefinic
      content by GC comparing the gas chromatograms of the original feed and
      hydrogenated product using a Petrocol-DH column. A decrease in the quantity and
      disappearances of the peaks are assumed as olefins, and their number and total
      composition is calculated. In this study the bromine number method is used to
      estimate the olefinic content for a comparison of results with the adopted
      proposed methodology. The adopted methodology quantitates olefinic content in FCC
      light gasoline, which is comparable with reported literature values and the
      bromine number method. With the availability of standard reference samples of
      some important major reactive olefins, the adopted methodology can also give
      component-wise analysis as well as total olefinic content in a single step in
      processes such as etherification. The methodology can be also useful in reactions
      in which the conversion of total olefinic content is needed such as hydration,
      esterification, and alkylation of olefins in a complex mixture of hydrocarbons
      apart from the etherification of olefins in FCC gasoline.

PMID- 12201479
TI  - Solvent effects on the screening of parallel combinatorial libraries for
      selectors for chiral chromatography.
AB  - The correlation between the resin-swelling property and the outcome of the
      crucial equilibration assay used in our parallel library screening method is
      investigated. It is found that the incorporation of CHCl3 (an effective swelling
      solvent for both the polystyrene and TentaGel resins) into the equilibration
      solvent leads to faster equilibration and thus shorter library screening time.
      The outcome of the equilibration experiment is also found to depend on the
      chemical nature of the solid base resins. It appears that polystyrene resin,
      which has a relatively inert surface, provides higher enantioselectivity than the
      polar TentaGel resin. The importance of a thoroughly swelled resin for the direct
      assay of functional groups on the resin is demonstrated.

PMID- 12201480
TI  - Determination of acidic herbicides in surface water by solid-phase extraction
      followed by capillary zone electrophoresis.
AB  - A rapid solid-phase extraction-capillary zone electrophoresis (CZE) method for
      determining 2,4-dichlorophenoxyacetic acid, 4-(2,4-dichlorophenoxy) butyric acid,
      and 2,4,5-trichlorophenoxyacetic acid in real water samples is described. Factors
      affecting the recoveries and detection of the targets are investigated. With
      samples being acidified to pH 2 and salted by sodium sulfate to 2% (w/w), an
      average recovery of greater than 85% is obtained using ethyl acetate as the
      eluent on an octadecylsilane-bonded silica cartridge. A running buffer of 5 mM
      sodium tetraborate in a water-acetonitrile mixture (70:30, v/v) adjusted to pH 9
      is employed in the CZE analysis, and the targets can be analyzed within 7 min
      with good reproducibility and acceptable sensitivity. The method is suitable for
      detecting herbicide residues of sub-parts-per-billion levels in surface water. A
      local pond water is analyzed, and the concentrations of 2,4-dichlorophenoxyacetic
      acid and 4-(2,4-dichlorophenoxy) butyric acid are detected to be 0.27 +/- 0.03
      ppb and 0.61 +/- 0.08 ppb, respectively.

PMID- 12201481
TI  - Solid-phase extraction and cleanup of organophosphorus pesticide residues in
      bovine muscle with gas chromatographic detection.
AB  - The purpose of this investigation is to develop a rapid and simple method for the
      assessment of organophosphorus pesticides in bovine muscle by using solid-phase
      extraction (SPE). After extraction with ethyl acetate (EtOAc) the homogenate is
      centrifuged and filtered through sodium sulfate. The fat is precipitated in
      methanol by cooling and the extract is diluted with water and passed through a
      SPE column (Isolute ENV+). After elution with EtOAc, evaporation, and
      redissolution, the sample is injected into a gas chromatographic (GC) capillary
      column DB-1701 and detected by a flame photometric detector. Recoveries from
      bovine muscle fortified with 12 pesticides between 4 and 65 microg/kg include
      three levels ranging between 59% and 109% for ten of them. The two most polar
      pesticides (metamidophos and acephate) are not successful. The relative standard
      deviations are between 1% and 10% for the ten pesticides. A simplex method is
      used to optimize the GC conditions.

PMID- 12201482
TI  - A high-performance-liquid-chromatography-based method for the determination of
      hydroxylated testosterone metabolites formed in vitro in liver microsomes from
      gray seal (Halichoerus grypus).
AB  - A reproducible and sensitive high-performance-liquid-chromatography (HPLC)-based
      method with UV-vis detection is developed and optimized for the determination of
      hydroxytestosterone compounds formed via the cytochrome P450 enzyme-mediated
      metabolism of testosterone. The method is used to characterize and quantitate
      hydroxytestosterone metabolites formed in vitro via testosterone incubation with
      hepatic microsomes from the liver of gray seals (Halichoerus grypus). The HPLC
      method employs a Zorbax Eclipse XDB-C18 column (5 microm, 250- x 4.6-mm i.d.) and
      a combination of step gradient and solvent systems of mixtures of acetonitrile,
      methanol, and water. Metabolites are detected at 254 nm. The eluted peaks of 10
      testosterone metabolite standards are well-resolved and a flat baseline is
      maintained over the elution period of the entire chromatogram. The instrumental
      detection limits (signal-to-noise ratio = 3) of 6beta-, 16beta-, 16alpha-, and
      7alpha-hydroxytestostone and androstenedione are 14, 3, 3, 14, and 3 pmol (20
      microL injection), respectively. Eleven hydroxytestosterone metabolites are
      detected after in vitro testosterone incubation with hepatic microsomes of gray
      seals. Six are identified as 6beta-, 7alpha-, 16alpha-, 16beta-, and 2beta
      hydroxytestosterone and androstenedione. In order of abundance, the formation
      rates are 2100, 39.6, 12.8, 26.2, and 132 pmol/mg protein/min for 6beta-, 7alpha
      , 16alpha-, and 16beta-hydroxytestosterone and androstenedione, respectively. The
      within-day precision (relative standard deviation) is less than 3% for
      testosterone metabolites. Five relatively substantial peaks are detected but not
      identified.

PMID- 12201483
TI  - Analysis of polycyclic aromatic hydrocarbons in the particulate phase of
      cigarette smoke using a gas chromatographic-high-resolution mass spectrometric
      technique.
AB  - A new procedure is developed for the extraction of polycyclic aromatic
      hydrocarbons (PAHs) from the particulate phase of cigarette smoke. The procedure
      applies solid-phase extraction using a Bond Elut CH cartridge as a sample
      preparation step. The efficiency of the cleanup procedure is verified using a gas
      chromatographic (GC)-high-resolution mass spectrometric (MS) technique, proving
      that no interference occurs in the PAHs' determination. The efficient cleanup
      allows GC detection using either high- or low-resolution MS detection. Enhanced
      sensitivity is obtained using GC-MS and selected ion monitoring. This new
      technique has several advantages over other reported techniques. The method is
      simple and robust and has good repeatability and accuracy. The estimated
      detection limit is 0.1 ng/cigarette for benzo[a]pyrene. In addition to that, the
      recovery from the smoke pad in which the smoke is collected is approximately 97%
      for all PAHs. Results for the PAH analyses for 1R5F, 1R4F, and 1R3 Kentucky
      reference cigarettes are reported in this study. These results provide useful
      evidence for clarifying the controversy about previously reported data.

PMID- 12201484
TI  - Isolation of a new member of the ecdysteroid glycoside family: 2-deoxy-20
      hydroxyecdysone 22-O-beta-D-glucopyranoside.
AB  - A new ecdysteroid glycoside, 2-deoxy-20-hydroxyecdysone 22-O-beta-D
      glucopyranoside, is isolated from the herb Silene italica ssp. nemoralis (Waldst.
      and Kit.) Nyman. The compound is purified with multistep chromatography, such as
      classical column chromatography on alumina and droplet countercurrent
      distribution. Also, it is expanded using twice low-pressure reversed-phase liquid
      column chromatography. Chromatography in four steps results in the purified 2
      deoxy-20-hydroxyecdysone 22-O-beta-D-glucopyranoside. Two other ecdysteroids have
      also been separated, including the formerly identified integristerone A and
      24(28)-dehydromakisterone A.

PMID- 12201485
TI  - What is the difference between an endcapped and a nonendcapped C18 column?

PMID- 12201486
TI  - Sulfinosine-induced cell growth inhibition and apoptosis in human lung carcinomas
      in vitro.
AB  - In spite of tremendous effort for improved therapy, lung cancer remains the
      leading cause of cancer-related deaths worldwide. In the present study, we used
      the novel purine ribunocleoside sulfinosine and evaluated its antiproliferative
      and apoptotic outcome on the non-small cell lung carcinoma cell line (NSCLC) and
      the small cell lung carcinoma cell line (SCLC). Using a BrdU incorporation-test
      sulfinosine inhibited cell growth in a dose dependent-manner. ID50 values were
      4.65 +/- 0.17 microM in the case of NSCLC cells, and 3.59 +/- 0.81 microM in the
      case of SCLC cells. MTT testing revealed that IC50 values were 6.24 +/- 0.77
      microM for NSCLC and 5.68 +/- 0.58 microM for SCLC. Inhibitory concentrations
      (IC50 and ID50) for sulfinosine were nonsignificantly lower in SCLC cells
      compared to NSCLC cells, indicating similar susceptibility of the cells. Flow
      cytometric analysis, TUNEL staining, DNA laddering and cell death ELISA test were
      used to investigate apoptotic cell death. Our results demonstrated that high
      concentrations of sulfinosine can cause typical DNA laddering, a hallmark for
      apoptosis. Evidence of free nucleosomes and enzymatic labeling of fragmented DNA
      confirmed apoptosis involvement in sulfinosine cytotoxicity. In addition, flow
      cytometric analysis showed that 25 microM sulfinosine arrested cell cycle
      progression at the G2M phase and induction of apoptosis in both cell lines. From
      these results, we concluded that sulfinosine may act as an anticancer agent and
      further studies may prove its efficacy in lung cancer cells. Thus the biological
      effects of sulfinosine may be due to modulation of cell growth, cell death, and
      cell cycle regulatory molecules.

PMID- 12201488
TI  - A novel high-through-put assay for screening of pro-apoptotic drugs.
AB  - Screening for anti-cancer substances is commonly conducted using viability
      assays. An inherent problem with this approach is that all compounds that are
      toxic and growth inhibitory, irrespective of mechanism of action, will score
      positive. It would be beneficial to be able to screen for compounds that
      specifically induce apoptosis. We here describe an ELISA-assay based on a
      monoclonal antibody (M30) which recognizes a neo-epitope on cytokeratin 18
      exposed after cleavage by caspases during apoptosis. We show that this assay
      detects apoptosis in epithelial cells and that the sensitivity is sufficient for
      screening in the 96-well format. We used the M30-ELISA assay to screen 500 low
      molecular weight compounds from a chemical library from the National Cancer
      Institute and identified 16 drugs with strong pro-apoptotic activity, suggesting
      that the assay is a useful tool for discovery of pro-apoptotic drugs.

PMID- 12201487
TI  - Antiangiogenic and antitumor effects of a protein kinase Cbeta inhibitor in human
      breast cancer and ovarian cancer xenografts.
AB  - In cell culture, the compound 317615 2HCl, a potent inhibitor of VEGF-stimulated
      HUVEC proliferation, was not very effective against MX-1 breast cancer cells
      (IC50= 8.1 microM) or SKOV-3 ovarian carcinoma cells (IC50 = 9.5 microM).
      Exposure to combinations of paclitaxel or carboplatin and 317615 x 2HCl with MX-1
      cells in culture resulted in cell survival that reflected primarily additivity of
      the two agents. Exposure of SKOV-3 cells to paclitaxel or carboplatin along with
      317615 2HCl resulted in cell survivals that reflected additivity of 317615 x 2HCl
      with paclitaxel and greater-than-additive cytotoxicity with carboplatin.
      Administration of 317615 x 2HCI orally twice daily to nude mice bearing
      subcutaneous MX-1 tumors or SKOV-3 tumors resulted in a decreased number of
      intratumoral vessels as determined by CD31 and CD105 staining with decreases of
      35% and 43% in MX-1 tumors and 60% and 75% in SKOV-3 tumors, respectively. 317615
      x 2HCl was an active antitumor agent against the MX-1 xenograft and increased the
      tumor growth delay produced by paclitaxel by 1.7-fold and the tumor growth delay
      produced by carboplatin by 3.8-fold. Administration of 317615 x 2HCl also
      increased the tumor growth delay produced by fractionated radiation therapy in
      the MX-1 tumor. Treatment with 317615 x 2HCl alone increased the lifespan of
      animals bearing intraperitoneal SKOV-3 xenografts by 1.9 fold compared with
      untreated control animals. The combination of paclitaxel and 317615 x 2HCl
      resulted in 100% 120-day survival of SKOV-3 bearing animals. Administration of
      317615 x 2HCl along with carboplatin to animals bearing the SKOV-3 tumor produced
      a 1.8-fold increase in lifespan compared with carboplatin alone. 317615 x 2HCl is
      a promising new antiangiogenic agent that is in early phase clinical testing.

PMID- 12201489
TI  - Preclinical antitumor activity and pharmacokinetics of methyl-2
      benzimidazolecarbamate (FB642).
AB  - Methyl-2-benzimidazolecarbamate (carbendazim, FB642) is an anticancer agent that
      induces apoptosis of cancer cells. In vitro, FB642 demonstrated potent antitumor
      activity against both the murine B16 melanoma (IC50 = 8.5 microm) and human HT-29
      colon carcinoma (IC50 = 9.5 microm) cell lines. FB642 was also highly active
      against both murine tumor models and human tumor xenografts at varying doses and
      schedules. In the murine B16 melanoma model, T/C values > 200 were observed. In
      the human tumor xenograft, FB642 produced tumor growth inhibition of greater than
      58% in five of the seven xenograft models evaluated. Partial and complete tumor
      shrinkage was noted with FB642 against the MCF-7 breast tumor model.
      Pharmacokinetic studies in rats demonstrated that oral absorption of FB642 was
      variable and may be saturated at the 2000 mg/kg dose level since higher doses
      failed to produce a further increase in the area under the time concentration
      curve. Toxicity of FB642 in vivo appeared to be dose-dependent. Lower doses in
      the range of 2,000-3,000 mg/kg were better tolerated, while still preserving
      antitumor activity. Evaluation of FB642 in phase I clinical trials of adult
      patients with advanced malignancies is currently ongoing.

PMID- 12201490
TI  - Enhanced antitumor activity of irofulven in combination with antimitotic agents.
AB  - The aim of this study was to determine the antitumor activity of irofulven when
      administered in combination with a variety of antimitotic agents. Irofulven in
      combination with either paclitaxel or docetaxel demonstrated synergistic activity
      in both the in vitro and in vivo studies. The majority of xenograft bearing
      animals that received suboptimal (< MTD) doses of irofulven and a taxane
      demonstrated complete cures. In contrast, in vitro studies produced either an
      additive or an antagonistic effect when irofulven was combined with other
      antimitotic agents such as vinca alkaloids, rhizoxin, s-trityl cysteine, or
      allocolchicine. Xenograft studies of irofulven and vinca alkaloids reflected in
      vitro results, as the tumor response in combination treated animals was less than
      the response in irofulven (monotherapy) treated animals. These results indicate
      that the therapeutic activity of irofulven is enhanced when combined with
      taxanes, and warrant further evaluation of these combinations.

PMID- 12201491
TI  - 5,6-dimethylxanthenone-4-acetic acid (DMXAA): a new biological response modifier
      for cancer therapy.
AB  - The investigational anti-cancer drug 5,6-dimethylxanthenone-4-acetic acid (DMXAA)
      was developed by the Auckland Cancer Society Research Centre (ACSRC). It has
      recently completed Phase I trials in New Zealand and UK under the direction of
      the Cancer Research Campaign's Phase I/II Clinical Trials Committee. As a
      biological response modifier, pharmacological and toxicological properties of
      DMXAA are remarkably different from most conventional chemotherapeutic agents.
      Induction of cytokines (particularly tumour necrosis factor (TNF-alpha),
      serotonin and nitric oxide (NO)), anti-vascular and anti-angiogenic effects are
      considered to be major mechanisms of action based on in vitro and animal studies.
      In cancer patients of Phase I study, DMXAA also exhibited various biological
      effects, including induction of TNF-alpha, serotonin and NO, which are consistent
      with those effects observed in in vitro and animal studies. Preclinical studies
      indicated that DMXAA had more potent anti-tumour activity compared to flavone-8
      acetic acid (FAA). In contrast to FAA that did not show anti-tumour activity in
      cancer patients, DMXAA (22 mg/kg by intravenous infusion over 20 min) resulted in
      partial response in one patient with metastatic cervical squamous carcinoma in a
      Phase I study where 65 cancer patients were enrolled in New Zealand. The maximum
      tolerated dose (MTD) in mouse, rabbit, rat and human was 30, 99, 330, and 99
      mg/kg respectively. The dose-limiting toxicity of DMXAA in cancer patients
      included acute reversible tremor, cognitive impairment, visual disturbance,
      dyspnoea and anxiety. The plasma protein binding and distribution into blood
      cells of DMXAA are dependent on species and drug concentration. DMXAA is
      extensively metabolised, mainly by glucuronidation of its acetic acid side chain
      and 6-methylhydroxylation, giving rise to DMXAA acyl glucuronide (DMXAA-G), and 6
      hydroxymethyl-5-methylxanthenone-4-acetic acid (6-OH-MXAA), which are excreted
      into bile and urine. DMXAA-G has been shown to be chemically reactive, undergoing
      hydrolysis, intramolecular migration and covalent binding. Studies have indicated
      that DMXAA glucuronidation is catalysed by uridine diphosphate
      glucuronosyltransferases (UGT1A9 and UGT2B7), and 6-methylhydroxylation by
      cytochrome P450 (CYP1A2). Non-linear plasma pharmacokinetics of DMXAA has been
      observed in animals and patients, presumably due to saturation of the elimination
      process and plasma protein binding. Species differences in DMXAA plasma
      pharmacokinetics have been observed, with the rabbit having the greatest plasma
      clearance, followed by the human, rat and mouse. In vivo disposition studies in
      these species did not provide an explanation for the differences in MTD. Co
      administration of DMXAA with other drugs has been shown to result in enhanced
      anti-tumour activity and alterations in pharmacokinetics, as reported for the
      combination of DMXAA with melphalan, thalidomide, cyproheptadine, and the
      bioreductive agent tirapazamine, in mouse models. Species-dependent DMXAA
      thalidomide pharmacokinetic interactions have been observed. Co-administration of
      thalidomide significantly increased the plasma area of the plasma concentration
      time curve (AUC) of DMXAA in mice, but had no effect on DMXAA's pharmacokinetics
      in the rat. It appears that the pharmacological and toxicological properties of
      DMXAA as a new biological response modifier are unlikely to be predicted based on
      preclinical studies. Similar to many biological response modifiers, DMXAA alone
      did not show striking anti-tumour activity in patients. However, preclinical
      studies of DMXAA-drug combinations indicate that DMXAA may have a potential role
      in cancer treatment when co-administered with other drugs. Further studies are
      required to explore the molecular targets of DMXAA and mechanisms for the
      interactions with other drugs co-administered during combination treatment, which
      may allow for the optimisation of DMXAA-based chemotherapy.

PMID- 12201492
TI  - A phase I and pharmacologic study of pyrazoloacridine (NSC 366140) and
      carboplatin in patients with advanced cancer.
AB  - BACKGROUND: Pyrazoloacridine (PZA) is the first of a new class of rationally
      synthesized acridine derivatives to undergo clinical testing as an anticancer
      agent. We previously demonstrated cytotoxic synergy between combinations of PZA
      and platinum compounds. Subsequent studies revealed that PZA inhibits removal of
      platinum-DNA adducts in cultured A549 cells. Based on these results, we undertook
      a phase I study of the combination of PZA and carboplatin (CBDCA). PATIENTS AND
      METHODS: Twenty-eight patients received 76 28-day courses (median 2.5, range 1-6)
      of CBDCA (30-minute infusion) followed by PZA (3-hour infusion), through six dose
      levels [PZA/CBDCA] (200/AUC 3, 400/AUC 3, 400/AUC 4, 400/AUC 5, 500/AUC 5,
      600/AUC 5 mg/m2/AUC). Pharmacokinetic analyses were performed to evaluate the
      disposition of PZA. Retention of platinum-DNA adducts in peripheral blood
      mononuclear cells of patients was also evaluated. RESULTS: The most common and
      dose-limiting toxicity was myelosuppression, consisting of neutropenia and
      leukopenia. Non-hematologic toxicities of anorexia, nausea and stomatitis were
      mild to moderate. In six patients evaluated at the MTD, CBDCA did not appear to
      affect the pharmacokinetics of PZA. One patient with malignant melanoma had a
      partial response. Disease stabilization for greater than 4 courses of treatment
      occurred in 4 patients. CONCLUSION: The combination of PZA and CBDCA was well
      tolerated and may have utility in some tumor types.

PMID- 12201493
TI  - A report on serious pulmonary toxicity associated with gemcitabine-based therapy.
AB  - BACKGROUND: Serious pulmonary toxicity (SPT) has recently been noted with
      gemcitabine-based therapy (G). However, the incidence of SPT has not been fully
      evaluated. This retrospective review estimates the incidence of, and the factors
      influencing, SPT with G. PATIENTS AND METHODS: Pulmonary toxicity was defined as
      dyspnea, interstitial pneumonitis, lung disorder, lung edema, lung fibrosis,
      pneumonia, respiratory disorder, and respiratory distress syndrome. Patients were
      identified from 2 worldwide Lilly databases--the clinical trial database (CTD)
      and the safety database (SD). Events designated as serious and possibly/probably
      related to therapy by the primary physician were independently evaluated and
      confirmed. Serious pulmonary toxicity events were categorized as dyspnea or other
      SPT events. RESULTS: Of the 91 patients identified by the investigator in the CTD
      as having G-related SPT, 32 had G-related SPT per the independent reviewers.
      Based on the 4448 patients treated with G in the CTD, the incidences of dyspnea
      and other SPT events were 0.45% and 0.27%, respectively. Of the 295 patients
      identified by the investigator in the SD as having G-related SPT, 167 had G
      related SPT per the independent reviewers. Based on an estimated 217,400 patients
      treated with commercial G worldwide, the crude incidences of dyspnea and other
      SPT events were 0.02% and 0.06%, respectively. CONCLUSIONS: SPT associated with G
      is uncommon. Incidences from the CTD for dyspnea and other SPT are 0.45% and
      0.27%, respectively. Incidences from the SD for dyspnea and other SPT are 0.02%
      and 0.06%, respectively. The influence of other factors, such as anticancer
      therapies, on these incidences needs to be better understood.

PMID- 12201494
TI  - Phase I/II study of gemcitabine and vinorelbine plus cisplatin in non-small cell
      lung cancer.
AB  - PURPOSE: We determine the maximum tolerated dose (MTD) and efficacy of
      gemcitabine plus vinorelbine combined with cisplatin in patients with non-small
      cell lung cancer (NSCLC). PATIENTS AND METHODS: Chemo naive patients with stage
      IIIA to IV non-small cell lung cancer received outpatient administration of
      gemcitabine 1,000 mg/m2 and vinorelbine 25 mg/m2 intravenously on days 1 and 8
      every 21 days. Doses of gemcitabine and vinorelbine were escalated by 250 mg/m2
      and 5 mg/m2, respectively, at each dose level. Cisplatin was administered at a
      fixed dose of 50 mg/m2 on days 2 and 9. After the MTD was reached, the study was
      continued as a phase II trial. RESULTS: From January 1998 to March 1999, sixty
      five patients were enrolled. The first 38 patients participated in the phase I
      evaluation. After 130 cycles, the dose-limiting toxicities were neutropenia,
      stomatitis, asthenia, and hepatotoxicity occurring at the third and fourth dose
      levels (doses of gemcitabine/vinorelbine of 1,500/25 and 1,000/30 mg/m2). For the
      subsequent phase II evaluation, 27 additional patients, out of a total of 53,
      receiving the MTD of gemcitabine and vinorelbine (1000-1250/25 mg/m2) followed
      (24 hours later) by cisplatin 50 mg/m2. Thirty one (58%) of 53 assessable
      patients responded. Objective response for patients with stages III and IV
      disease, respectively, were 65% and 47%. The median time to progression and the
      overall survival time were 9 months (95% CI: 5-12) and 11 months (95% CI: 9-13),
      respectively. World Health Organization toxicity > or = grade 3 neutropenia was
      registered in 28 (54%) of 52 assessable patients (2% with febrile neutropenia),
      and > or = grade 3 thrombocytopenia in 15 (29%) patients (4% with bleeding).
      Nausea/vomiting (> or = grade 2) and asthenia (moderate to severe) occurred in 24
      (46%) and 14 (27%) patients, respectively. CONCLUSION: Gemcitabine 1,000-1,250
      mg/m2 plus vinorelbine 25 mg/m2 on days 1 and 8, followed by cisplatin 50 mg/m2
      24 hours later, is safe for outpatient administration and active in patients with
      NSCLC.

PMID- 12201495
TI  - Phase II trial of arsenic trioxide in patients with metastatic renal cell
      carcinoma.
AB  - Fourteen patients with metastatic renal cell carcinoma (RCC) were treated on a
      Phase II trial with arsenic trioxide (As2O3). Eligible patients had metastatic
      renal cell carcinoma with bidimensionally measurable disease, a Karnofsky
      performance status of at least 70%, life expectancy of greater than three months,
      and no evidence of brain metastases. Arsenic trioxide was given intravenously at
      a dose of 0.3 mg/kg/day for five consecutive days every four weeks. The most
      common toxicity observed was grade II elevation in liver function tests (36%),
      anemia (21%), renal insufficiency (14%), rash (7%), and diarrhea (7%). Best
      response was stable disease in 3 patients with one patient remaining on study at
      8+ months At the dose and schedule used in this trial, arsenic trioxide did not
      achieve a complete or partial response in metastatic renal cell carcinoma.

PMID- 12201496
TI  - A phase II study of caelyx (liposomal doxorubicin) in metastatic carcinoma of the
      prostate: tolerability and efficacy modification by liposomal encapsulation.
AB  - A single centre phase II study was conducted to determine the toxicity and
      activity of Caelyx in hormone refractory metastatic prostate cancer. Doxorubicin
      is known to be active in this setting and liposomal encapsulation may enhance its
      therapeutic efficacy and also reduce toxicity. Fourteen patients with hormone
      refractory metastatic prostate cancer were treated with CaelyxTM 50 mg/m2 once
      every four weeks. All patients had radiologically proven bone metastases and
      three also had soft tissue metastatic disease. All patients were evaluable for
      toxicity and response was assessable in thirteen cases. Three PSA responses were
      documented in patients with non-measurable disease. No patient had an objective
      response in measurable disease. The commonest toxicity was cutaneous and this was
      dose limiting in two patients. Gastrointestinal upset was frequent but generally
      mild. One patient died shortly after an episode of neutropaenic sepsis with
      associated grade 3 mucositis following his third cycle of chemotherapy. We
      confirmed the toxicity profile of Caelyx but its modest antitumour efficacy in
      this group of patients suggests little promise for future study in metastatic
      prostate cancer.

PMID- 12201497
TI  - Phase II trial of pyrazoloacridine in advanced non-small cell carcinoma of the
      lung--a Kansas Cancer Institute and Thompson Cancer Survival Center Study.
AB  - BACKGROUND: More active agents are needed in the treatment of metastatic non
      small cell lung cancer. Pyrazoloacridine (PZA) is a 9-methoxy acridine compound
      containing a reducible 5-nitro substituent. Although the mechanism of action of
      PZA is unknown, the acridine compounds are known to cause cytotoxicity by
      interaction with DNA and RNA. METHODS: Eighteen patients with metastatic non
      small cell lung carcinoma were treated with pyrazoloacridine. Pyrazoloacridine
      was administered as a three-hour infusion at 750 mg/M2 every 21 days. RESULTS:
      There were no objective responses. One patient maintained stable disease for 20
      months. Median survival was 4.8 months. The primary toxicity was granulocytopenia
      with 5 patients experiencing severe infections. CONCLUSIONS: Pyrazoloacridine has
      no demonstrable activity in patients with metastatic non-small cell carcinoma of
      the lung when given at this dose and schedule.

PMID- 12201498
TI  - A phase I study of SPI-077 (Stealth liposomal cisplatin) concurrent with
      radiation therapy for locally advanced head and neck cancer.
AB  - BACKGROUND: Liposomal cisplatin preparations have two potential advantages over
      the free drug when combined with radiation therapy (RT): 1) selective tumor
      localization, improving the therapeutic ratio, and 2) prolonged half-life,
      allowing more radiosensitization. We performed a Phase I study of Stealth
      liposomal cisplatin (SPI-077) concurrent with RT for head and neck squamous cell
      carcinoma (HNSCC). METHODS: Patients with Stage IVa/b HNSCC were treated with SPI
      077, given intravenously twice two weeks apart, concurrent with RT (60-72 Gy in 6
      7 weeks). The SPI-077 dose was escalated in standard phase I design. RESULTS:
      Twenty patients received 38 doses of SPI-077, escalated from 20-200 mg/m2 in six
      dose levels. Two of these patients received one dose because of reversible Grade
      3 liver toxicity or rash. Three patients had a Grade 1, and one had a Grade 2
      infusion reaction. Four patients had transiently elevated transaminases: Grade I
      (n = 1), Grade 2 (n = 1), and Grade 3 (n = 2). Grade 3 neutropenia occurred in
      one patient. There was no ototoxicity, neurotoxicity, or nephrotoxicity. In-field
      radiation skin and mucosal toxicities did not appear to be intensified. Ten of 17
      patients (59%) finishing treatment achieved initial complete response.
      CONCLUSIONS: Systemic and in-field radiation toxicities of SPI-077 were minimal.
      Infusion reactions were minimized with a slower and more dilute initial infusion.
      Further dose escalation was stopped in the absence of dose-limiting toxicity to
      address the reformulation of the liposomally bound cisplatin. Nonetheless, this
      study shows that high doses of SPI-077 can be given safely. The potentially
      beneficial therapeutic ratio suggests that liposomal radiosensitizer preparations
      warrant further investigation.

PMID- 12201499
TI  - Outpatient therapy with gemcitabine and docetaxel for gallbladder, biliary, and
      cholangio-carcinomas.
AB  - PURPOSE: The prognosis of patients with biliary tree carcinomas is very poor. The
      diagnosis often occurs at an advanced stage, when curative resection is not
      possible. We combined gemcitabine and docetaxel to optimize the palliative
      therapy for patients with gallbladder, biliary, and cholangio-carcinomas on an
      outpatient basis. PATIENTS AND METHODS: Patients with histologically proven
      biliary tree carcinomas and a WHO performance status <2 received gemcitabine 1000
      mg/m2 followed by docetaxel 35 mg/m2 weekly for 3 weeks followed by I week of
      rest. RESULTS: Forty-three patients, 14 males/29 females, with an average age of
      63.3 years (range, 41 to 78) have been enrolled since 1998; 37 have completed
      treatment. So far, 168 cycles (range, 1 to 16) have been administered. All 43
      patients were included in the response and toxicity assessments. There are no
      complete remissions; however, 4 (9.3%) patients achieved partial remission, 1
      (2.3%) had a minimal remission, and 24 (55.8%) reached disease stabilization for
      a median period of 5.2 months. Fourteen (32.6%) patients progressed. The median
      overall survival rate is currently 11.0 months. Grade 3 hematologic toxicities
      were infrequent, and there were no grade 4 hematologic toxicities. Grade 3
      leukopenia was reported in 4 (9.3%) patients, grade 3 thrombozytopenia in 1
      (2.3%) patient, and grade 3 anemia in 1 (2.3%) patient. Twenty-eight (65.1%)
      patients had grade 3/4 alopecia, 8 (18.6%) had nausea/vomiting, and 2 (4.6%) had
      mucositis. CONCLUSION: The combination of gemcitabine/docetaxel is an effective
      and well tolerated therapy for patients with advanced or metastatic gallbladder,
      biliary, and cholangio-carcinomas.

PMID- 12201500
TI  - A phase II study of Irofulven (MGI 114) in patients with stage IV melanoma.
AB  - Sixteen patients with stage IV melanoma, who were heavily pretreated, received 11
      mg/m2/day of intravenous Irofulven for five consecutive days every 28 days. There
      were no objective tumor responses, although one patient exhibited stable disease
      after 4 cycles. The most common toxicities were grade 1/2 nausea, vomiting,
      fatigue, anemia, and thrombocytopenia. One patient required a dose reduction for
      an elevated creatinine while another patient required cessation of treatment
      because of acute ataxia that may have been related to Irofulven. Based upon these
      data, Irofulven does not demonstrate significant antitumor activity to warrant
      further investigation in advanced melanoma.

PMID- 12201501
TI  - Physicians' response to victims of domestic violence: toward a model of care.
AB  - Even though current domestic violence guidelines, such as those published by the
      AMA in 1992, attempt to relieve physicians of the "full burden of intervention,"
      they continue to call upon physicians to play a large role in identifying,
      intervening in, and following up on case of partner abuse. In this paper, we
      define a limited domestic violence role for physicians which furthers the
      direction recommended by the AMA and which complements exemplary programs. We
      propose simplifying and limiting physicians' tasks to Asking patients about
      abuse; providing Validating messages, acknowledging that battering is wrong and
      confirming patient worth; Documenting presenting signs, symptoms, and
      disclosures; and Referring victims to domestic violence specialists (AVDR). By
      drawing on the literature and our own experience, we show how focusing the
      physician's role on these four taks is consistent with exemplary programs and
      expands on ideas put forth by experts for addressing domestic violence in health
      care settings; reduces barriers for physician interventions with victims; offers
      a realistic approach for physicians, reducing unrealistic educational demands;
      and complements managed care trends in contemporary health care.

PMID- 12201502
TI  - Assessing the success of the WomanKind program: an integrated model of 24-hour
      health care response to domestic violence.
AB  - PURPOSE: The WomanKind program, a non-profit health care based program for for
      victims of domestic/intimate partner violence (IPV), seeks to enable and motivate
      health care providers to identify victims of such violence and refer them to
      WomanKind's in-house services. An evaluation designed to assess client referral
      to WomanKind services and the impact of health care provider training was carried
      out. METHODS: Data were collected at three intervals over a 2-year period at 3
      intervention and 2 comparison hospitals located in Minneapolis, MN. The focus of
      data collection efforts was to assess the providers' knowledge, attitudes,
      beliefs, and behaviors (KABB) concerning identification and referral of victims
      of IPV. Hospital staff and volunteer advocate training programs also were
      evaluated. Chart reviews were conducted and client referrals assessed. RESULTS:
      Providers at WomanKind hospitals demonstrated significantly higher knowledge,
      attitudes, beliefs and behaviors than those at comparison hospitals throughout
      the study. During the data collection period, 1719 IPV victims were identified
      and referred to the WomanKind program, while only 27 IPV victims were referred to
      trained social workers at the comparison hospitals. Chart reviews indicated that
      emergency staff at the intervention sites provide documentation of IPV in patient
      records twice as frequently as emergency staff at the comparison sites.
      CONCLUSION: This research underscores the efficacy of a well-structured,
      multidisciplinary effort to deliver services to IPV victims. The results
      demonstrate that specialized training and on-site client services create a
      significant positive impact on the KABB of health care providers.

PMID- 12201503
TI  - A population-based survey assessing support for mandatory domestic violence
      reporting by health care personnel.
AB  - BACKGROUND: State laws mandating health care personnel to contact police when
      treating patients injured as a result of domestic violence are controversial.
      Attitudes toward these laws have been studied in select groups, but never in a
      large population-based sample. METHODS: We measured support for mandatory
      reporting (MR) among 845 women in 11 cities who participated in a telephone
      survey assessing risk factors for intimate partner violence. Abused women were
      oversampled to create equal groups (427 abused and 418 non-abused); results are
      presented stratified by abuse status or weighted based on prevalence of abuse
      among women who were screened. RESULTS: The estimated prevalence of physical
      violence or threat of physical violence from an intimate partner during the past
      two years was 11.7%; 72% (95% CI = 69%-75%) of women supported MR. Abused women
      were significantly less likely to support MR compared to non-abused women (59%
      versus 73%, p < 0.01). Reasons that endorsed support included: victims would find
      it easier to get help (81%) and would like health care personnel to call the
      police (68%). Reasons that endorsed opposition included: victims would be less
      likely to disclose abuse (77%), would resent someone else having control (61%),
      and reporting would increase the risk of perpetrator retaliation (44%).
      CONCLUSIONS: Most women support mandatory reporting by health care personnel.
      However, abused women were significantly less supportive than those not abused.

PMID- 12201504
TI  - Abused patient's attitudes about mandatory reporting of intimate partner abuse
      injuries to police.
AB  - OBJECTIVES: This study examines abused women's preferences regarding medical
      clinician reporting of intimate partner abuse injuries to police. It also
      examines the influence of specific demographic factors on abused women's
      reporting preferences. METHODS: Telephone interviews were conducted with a random
      sample of women patients attending one of three public primary care clinics
      associated with the San Francisco Community Health Network. Participants
      reporting a history of abuse were asked to identify their preferences regarding
      the reporting of abuse by medical clinicians to police. RESULTS: Of the 358
      abused women interviewed in this study, the majority of them (n = 243, 68%) did
      not prefer a domestic violence injury reporting system that was mandatory even if
      against patient wishes. However, almost all women (n = 329, 92%) favored some
      form of police reporting by medical clinicians. Women who had been abused within
      the past year were more likely to oppose mandatory reporting than women who had
      been abused more than one year ago. Younger women were more likely than older
      women to oppose mandatory reporting requirements, and women whose primary
      language was English were more likely to oppose mandatory reporting requirements
      than women whose primary language was Spanish. Current abuse was independently
      predictive of decreased likelihood to select mandatory reporting in all
      situations. There were no significant differences in reporting preferences by
      ethnicity, marital status, education, employment, or the presence of children at
      home. CONCLUSIONS: Despite broad support among abused women for medical clinician
      reporting of intimate partner abuse injuries to police, most women do not support
      mandatory reporting requirements that do not allow for consideration of the
      abused patients' wishes. More research is needed to ascertain whether the
      benefits of mandatory reporting outweigh the risks to those intended to benefit
      from the law.

PMID- 12201505
TI  - Physically abused pregnant women's perceptions about the quality of their
      relationships with their male partners.
AB  - OBJECTIVES: Most studies of pregnant victims of intimate partner violence have
      focused on the violent behaviors, without examining other potentially important
      dimensions of the relationships. This research studies pregnant abuse victims to
      examine the frequency of violent behaviors occurring during pregnancy, how women
      characterize the quality of their relationships, and the association between
      violence frequency and women's perceptions concerning the overall quality of
      their relationships. METHODS: Eighty-one women who were physically abused by
      intimate partners during pregnancy were interviewed. Information was collected
      concerning the women's: experiences of partner violence during pregnancy;
      perceptions of other aspects of the quality of their relationships; and
      sociodemographic characteristics. RESULTS: The most frequent type of violent
      behavior occurring during pregnancy was verbal aggression, followed by minor
      violence, and then severe violence. Men perpetrated each type of violent behavior
      at significantly higher rates than did their female partners. In general, the
      women were quite negative in their characterizations of many dimensions of their
      relationships, as well as in their perceptions concerning the overall quality of
      their relationships, with women who had been victims of more frequent violence
      being significantly more likely to characterize their relationships as being of
      lower overall quality (OR = 3.5, 95% CI = 1.4-8.7). CONCLUSIONS: Prenatal care
      providers are encouraged to screen their patients for intimate partner violence,
      and to work with others in their community to assure that women in abusive
      situations are offered appropriate services/interventions including safe and
      feasible alternatives to staying in unsatisfactory relationships with abusive
      partners.

PMID- 12201506
TI  - Severity of intimate partner abuse indicators as perceived by women in Mexico and
      the United States.
AB  - OBJECTIVE: Women in Cuernavaca, Mexico and Los Angeles, California were surveyed
      to examine differences in their perceptions of the severity of domestic violence
      indicators. METHODS: One hundred twenty women in each country rated the severity
      of 26 domestic violence indicators which were part of an abuse screen used for an
      ongoing study of the prevalence of abuse. Rasch analysis was conducted to
      determine the linear relationship in the perceptions of the severity of each
      event between the two countries. RESULTS: The Rasch calibrated logit values show
      that women in the US rated 24 of the 26 events as more severe than women in
      Mexico. However, items were ranked in similar order and a clear linear pattern
      was established. In both countries, being shot with a gun was the most severe
      event and a partner becoming jealous was the least severe. CONCLUSION: The
      country of origin did not dictate which events were most severe but did influence
      how severe these events were perceived.

PMID- 12201507
TI  - Testing an intimate partner violence assessment icon form with battered migrant
      and seasonal farmworker women.
AB  - A user-friendly assessment form using icons was developed for the Lideres
      Campesinas de California, Inc., a women farmworker organization in California,
      for assessing migrant and seasonal farmworker women for abuse. The purpose of
      this study was to test the reliability and validity of the form. Twenty-five
      women from the Lideres participated. The form, called the Intimate Partner
      Violence (IPV) Assessment Icon Form, was designed to be used with literate, semi
      literate, and illiterate women. Inter-rater reliability and criterion-related
      validity of the IPV Assessment Form were found to be adequate for the literate
      and semi-literate participants. There were not enough illiterate women (n = 2) to
      include in the analysis. This study also demonstrates that with adequate
      training, support, and tools, migrant and seasonal farmworker women can work in
      partnership with researchers to design, develop and conduct research in their own
      communities.

PMID- 12201508
TI  - Women referred for on-site domestic violence services in a managed care
      organization.
AB  - BACKGROUND: Limited data about victims of domestic violence in health care
      settings hinder development of appropriate services. A comprehensive program was
      established in a managed care organization to increase identification and
      referral of domestically abused female patients. METHODS: Female victims of
      domestic abuse were referred to a trained social worker for further assessment.
      Information about the women was obtained from clinical consultation forms;
      initial interviews conducted by social workers; a survey administered to a
      convenience sample of women seen by the program; and medical chart review.
      RESULTS: Of 265 women who agreed to a domestic violence referral, 177 (67%) were
      contacted for further evaluation. The study sample was ethnically diverse and
      included female victims seen for routine care, women who had been assaulted,
      women who had depression, and women with various somatic symptoms. Responses from
      51 of the 177 women showed the most cited reasons for accepting referral were
      unhappiness with current situation, wanting to leave or change the situation,
      concern about children who witnessed abuse, and the suggestion by a health care
      practitioner that the patient's symptoms could be related to the abuse. Most
      reported having symptoms of depression in the previous year. CONCLUSIONS:
      Comprehensive programs in the health care setting can increase identification of
      victims of domestic abuse. This descriptive report provides a greater
      understanding of victims of domestic abuse, their presentation in the medical
      setting, their motivation for accepting referral, and issues which affect their
      recovery. Links between health care and community resources are necessary for
      effective intervention.

PMID- 12201509
TI  - Domestic violence in later life: an overview for health care providers.
AB  - Domestic violence is a significant problem that adversely affects the health and
      safety of millions of women throughout their life-span. Most cases of what is
      considered elder abuse occurs at home rather than in institutions, and the
      evidence suggests that only 1 in 5 cases are recognized. Frequently the
      perpetrator is a spouse, adult child, or other family member. Given the
      demographics of aging women and their longer life expectancies, clinicians are
      increasingly likely to see patients whose injuries or poor health status are
      caused or affected by abusive relationships. Improving the ability of physicians
      to identify domestic violence is an important skill needed for establishing
      comprehensive intervention and prevention efforts. In addition to conducting
      universal screening of all female patients, using clinical and behavioral
      indicators is a critical component of the intervention.

PMID- 12201510
TI  - The impact of perceived barriers on primary care physicians' screening practices
      for female partner abuse.
AB  - OBJECTIVES: Our purpose was to examine primary care physicians' screening
      practices for female partner abuse in different clinical situations and to
      investigate the relationship between perceived barriers and screening practices.
      METHODS: A cross-sectional survey was mailed to Alaska physicians practicing in
      the following specialties: family practice, internal medicine,
      obstetrics/gynecology and general practice. RESULTS: The survey response rate was
      80 percent (305/383). The majority (85.7%) of primary care physicians screened
      often or always when a female patient presents with an injury, but they rarely
      screened at initial visits (6.2%) or annual exams (7.5%). More than one-third of
      respondents estimated that 10% or more of their female patients had experienced
      some type of intimate partner abuse. Several barriers to screening described in
      the literature were not predictive of physicians' screening practice patterns.
      Physicians' perceptions that abuse is prevalent among their patients and
      physicians' beliefs that they have a responsibility to deal with abuse were the
      only variables independently associated with screening at initial visits and
      annual exams. The only variable predictive of screening when a patient presents
      with an injury was physicians' perceived prevalence of abuse. CONCLUSION: Primary
      care physicians have not integrated screening for partner abuse into routine
      care. Strategies to increase awareness of the high prevalence of abuse in the
      primary care setting and to educate providers on the negative health effects of
      victimization can help physicians to acknowledge their responsibility in
      addressing abuse and the importance of screening at routine visits. Further
      rigorous studies are needed to identify and evaluate predictors of screening for
      abuse.

PMID- 12201511
TI  - Intimate partner violence from the emergency medicine perspective.
AB  - BACKGROUND: The incidence of acute cases of intimate partner violence (IPV) in
      the Emergency Department (ED) patients is between 2 and 7.2%. Ongoing IPV may be
      an immediate cause of presentation for medical care, or it may not be readily
      apparent. Over the last two decades efforts to improve identification of IPV in
      the ED have been successful. METHODS: A medline literature search from 1981-2001
      was performed. A review of intimate partner violence from the emergency
      department provider perspective is performed. A discussion of the
      screening/detection of intimate partner violence and the barriers to improving
      detection rates is provided. RESULTS: The review of the current literature shows
      that IPV is a frequent cause of illness or injury in patients presenting in the
      ED. Screening programs for intimate partner violence have shown to increase the
      identification of patients experiencing acute episodes of abuse and seeking
      treatment. The difficulty has been in sustaining the programs and improving the
      screening of patients. Patient, provider and systems barriers prevent adequate
      recognition and management of the problem. CONCLUSION: Detection of IPV in
      patients presenting to the ED can be improved by providing educational programs
      and screening tools to health care providers. Sustaining the screening programs
      is more difficult and requires a health care system-wide effort.

PMID- 12201512
TI  - Making family planning clinics an empowerment zone for rural battered women.
AB  - While domestic violence in rural areas is not different in kind or incidence from
      that found in urban areas of the country, rural women face unique difficulties in
      accessing health and social services when they experience abuse. We present an
      overview of rural life and the difficulties rural women face in accessing health
      care and other services. We describe the network of family planning clinics and
      domestic violence advocacy programs in western Pennsylvania and a pilot project
      designed to implement routine screening for domestic violence in family planning
      clinics in rural Pennsylvania. We report on changes in the staff's practice of
      and comfort with screening and making referrals during the initial six months of
      the program. Finally, we report on a partnership between the clinic and the
      domestic violence advocacy program in one county as a model for meeting the needs
      of rural women who experience abuse. This research supports recommendations that
      assessment and interventions for abuse be incorporated into rural health care
      systems.

PMID- 12201513
TI  - Scale-up of native beta-lactoglobulin affinity separation process.
AB  - Affinity separation of beta-lactoglobulin in its native form with all-trans
      retinal immobilized on calcium bio-silicate was scaled up and applied to separate
      it from industrial sweet whey. Three different methods of mixing the modified
      calcium bio-silicate and whey for the interaction between all-trans-retinal and
      beta-lactoglobulin were tried at pilot scale. The three methods used were 1) a
      column packed with calcium bio-silicate, 2) a stirred tank, and 3) a fluidized
      bed column of calcium bio-silicate particles. Adsorption and desorption of beta
      lactoglobulin were carried out at pH 5.1 and 7.0, using 0.01 and 0.1 M phosphate
      buffers, respectively. The phosphate buffer containing desorbed beta
      lactoglobulin was concentrated 20 times using ultrafiltration and then freeze
      dried. The packed column, stirred tank, and fluidized bed column produced beta
      lactoglobulin with purity of 80, >95, and >95%, and recovery of 0.65, 2.88, and
      2.88 g per kilogram of calcium bio-silicate, respectively. The comparative poor
      purity and recovery of beta-lactoglobulin in the case of the packed column was
      attributed to insufficient contact between the passing fluids and the calcium bio
      silicate during adsorption, desorption, and intermittent washing. The fluidized
      bed column method, with a gentle mixing action, was considered the best suited
      for further scale up to the industrial level.

PMID- 12201514
TI  - Effect of pH and calcium concentration on proteolysis in mozzarella cheese.
AB  - Low-moisture Mozzarella cheeses (LMMC), varying in calcium content and pH, were
      made using a starter culture (control; CL) or direct acidification (DA) with
      lactic acid or lactic acid and glucono-delta-lactone. The pH and calcium
      concentration significantly affected the type and extent of proteolysis in
      Mozzarella cheese during the 70-d storage period at 4 degrees C. For cheeses with
      a similar pH, reducing the calcium-to-casein ratio from -29 to 22 mg/g of protein
      resulted in marked increases in moisture content and in primary and secondary
      proteolysis, as indicated by polyacrylamide gel electrophoresis and higher levels
      of pH 4.6- and 5%-PTA-soluble N. Increasing the pH of DA cheeses of similar
      moisture content, from approximately 5.5 to 5.9, while maintaining the calcium-to
      casein ratio almost constant at approximately 29 mg/g, resulted in a decrease in
      primary proteolysis but had no effect on secondary proteolysis. Comparison of CL
      and DA cheeses with a similar composition showed that the CL cheese had higher
      levels of alpha(s1)-CN degradation, pH 4.6- and 5%-PTA-soluble N. Analysis of pH
      4.6-soluble N extracts by reverse-phase HPLC showed that the CL cheese had higher
      concentrations of compounds with low retention times, suggesting higher
      concentrations of low molecular mass peptides and free amino acids.

PMID- 12201515
TI  - Effect of pH and calcium concentration on some textural and functional properties
      of mozzarella cheese.
AB  - The effects of Ca concentration and pH on the composition, microstructural, and
      functional properties of Mozzarella cheese were studied. Cheeses were made using
      a starter culture (control) or by direct acidification of the milk with lactic
      acid or lactic acid and glucono-delta-lactone. In each of three trials, four
      cheeses were produced: a control, CL, and three directly-acidified cheeses, DA1,
      DA2, and DA3. The cheeses were stored at 4 degrees C for 70 d. The Ca content and
      pH were varied by altering the pH at setting, pitching, and plasticization. The
      mean pH at 1 d and the Ca content (mg/g of protein) of the various cheeses were:
      CL, 5.42 and 27.7; DA1, 5.96 and 21.8; DA2, 5.93 and 29.6; DA3, 5.58 and 28.7.
      For cheeses with a high pH (i.e., approximately 5.9), reducing the Ca content
      from 29.6 to 21.8 mg/g of protein resulted in a significant decrease in the
      protein level and increases in the moisture content and mean level of
      nonexpressible serum (g/g of protein). Reducing the Ca concentration also
      resulted in a more swollen, hydrated para-casein matrix at 1 d. The decrease in
      Ca content in the high-pH cheeses coincided with increases in the mean
      stretchability and flowability of the melted cheese over the 70-d storage period.
      The fluidity of the melted cheese also increased when the Ca content was reduced,
      as reflected by a lower elastic shear modulus and a higher value for the phase
      angle, delta, of the melted cheese, especially after storage for <12 d. The melt
      time, flowability, and stretchability of the low-Ca, high-pH DA1 cheese at 1 d
      were similar to those for the CL cheese after storage for > or = 12 d. In
      contrast, the mean values for flowability and stretchability of the high-pH, high
      Ca DA2 cheese over the 70-d period were significantly lower than those of the CL
      cheese. Reducing the pH of high-Ca cheese (27.7 to 29.6 mg/g of protein) from 
      5.95 to 5.58 resulted in higher flowability, stretchability, and fluidity of the
      melted cheese. For cheeses with similar pH and Ca concentration, the method of
      acidification had little effect on composition, microstructure, flowability,
      stretchability, and fluidity of the melted cheese.

PMID- 12201516
TI  - Variation in organic acids content during ripening of pickled white cheese.
AB  - Nine organic acids (formic, pyruvic, lactic, acetic, orotic, citric, uric,
      propionic, and butyric) were analyzed during ripening of pickled White cheese for
      12 mo by high-performance liquid chromatography with a reverse phase C18 (120x 5
      mm) column and UV detector. The level oftotal organic acids showed an increase
      along the ripening period, but its composition varied during the process.
      Initially, lactic acid accounted for 95% of the total, after 9 and 12 mo of
      ripening, butyric acid constituted 20 and 27% of the total, respectively. Each
      organic acid presented a characteristic pattern of change during ripening.
      Discriminant analysis classified cheeses according to their age. Stepwise
      regression analysis allowed estimation of the ripening time of samples according
      to their organic acid levels.

PMID- 12201517
TI  - Viscous properties of microparticulated dairy proteins and sucrose.
AB  - Slurries of whey protein concentrate (WPC) or sodium caseinate (Na-CN) mixed with
      sucrose (36% T.S.) were subjected to microparticulation by a high shear
      homogenizer operated at 27,000 rpm for 2, 4, and 6 min to facilitate gel
      formation. After microparticulation treatment, the milk protein and sucrose
      slurries were evaporated at 85 degrees C for 60 min under a partial vacuum (20 to
      45 mm of Hg) to form composite gels. Particle sizes and viscoelastic properties
      were determined before microparticulation treatment. Microparticulation reduced
      the particle size of WPC-sucrose slurries from an average size of 330 to 188 nm
      after 4 min and NaCN-sucrose slurries from 270 to 35 nm after 2 min. The WPC
      sucrose composites were gel-like, but NaCN-sucrose composites did not gel.
      Viscoelastic properties of heated WPC-sucrose composites were liquid-like,
      exhibiting significant reduction in storage modulus and complex viscosity.
      Microparticulation reduced particle sizes, which resulted in softer gels as time
      of shearing increased.

PMID- 12201518
TI  - Effect of double homogenization and whey protein concentrate on the texture of
      ice cream.
AB  - Ice cream samples were made with a mix composition of 11% milk fat, 11% milk
      solids-not-fat, 13% sucrose, 3% corn syrup solids (36 dextrose equivalent), 0.28%
      stabilizer blend, or 0.10% emulsifier and vanilla extract. Mixes were high
      temperature short time pasteurized at 80 degrees C for 25 s, homogenized at 141
      kg/cm2 pressure on the first stage and 35 kg/cm2 pressure on the second, and
      cooled to 3 degrees C. The study included six treatments from four batches of
      mix. Mix from batch one contained 0.10% emulsifier. Half of this batch (treatment
      1), was subsequently frozen and the other half (upon exiting the pasteurizer) was
      reheated to 60 degrees C, rehomogenized at 141 kg/cm2 pressure on the first stage
      and 35 kg/cm2 pressure on the second (treatment 2), and cooled to 3 degrees C.
      Mix from batch two contained 0.28% stabilizer blend. Half of this batch was used
      as the control (treatment 3), the other half upon exiting the pasteurizer was
      reheated to 60 degrees C, rehomogenized at 141 kg/cm2 pressure on the first stage
      and 35 kg/cm2 pressure on the second (treatment 4), and cooled to 3 degrees C.
      Batch three, containing 0.10% emulsifier and 1% whey protein concentrate
      substituted for 1% nonfat dry milk, upon exiting the pasteurizer was reheated to
      60 degrees C, rehomogenized at 141 kg/cm2 pressure on the first stage and 35
      kg/cm2 pressure on the second (treatment 5), and cooled to 3 degrees C. Batch
      four, containing 0.28% stabilizer blend and 1% whey protein concentrate
      substituted for 1% nonfat dry milk, upon exiting the pasteurizer was reheated to
      60 degrees C, rehomogenized at 141 kg/ cm2 pressure on the first stage and 35
      kg/cm2 pressure on the second (treatment 6), and cooled to 3 degrees C.
      Consistency was measured by flow time through a pipette. Flow time of treatment 3
      was greater than all treatments, and the flow times of treatments 4 and 6 were
      greater than treatments 1, 2, and 5. Flow time was increased in ice cream mix by
      the addition of stabilizer. Double homogenization lowered ice cream mix flow time
      in the presence of stabilizer, but no difference in flow time was observed
      without stabilizer addition. Treatment 4 had a lower mean ice crystal size at 10
      d postmanufacture compared with treatment 3; however, overall texture
      acceptability between treatments 3 and 4 was similar. Mean ice crystal size of
      treatment 6 was less at 18 wk postmanufacture compared with treatment 3; however,
      overall texture acceptability for treatments 3, 4, and 6 was similar. Mean ice
      crystal sizes of treatments 1, 2, and 5 were greater at 10 d and 18 wk compared
      with treatment 3. Sensory evaluation indicated that treatments 3, 4, and 6 had
      higher mean scores for icy, coldness intensity, and creaminess than treatments 1,
      2, and 5 at 10 d and 18 wk postmanufacture.

PMID- 12201519
TI  - Nondestructive measurement of light-induced oxidation in dairy products by
      fluorescence spectroscopy and imaging.
AB  - The purpose of this paper is to demonstrate the potential of solid-sample
      fluorescence spectroscopy in nondestructive assessment of light-induced oxidation
      in different dairy products such as Swiss cheese, cream cheese, and sour cream.
      Analytical and quantitative spectral properties of fluorescence were elucidated
      by use of principal component analysis with designed experiments involving
      different levels of air and light exposure. A significant reduction in
      fluorescence intensity at approximately 525 nm, and a corresponding increase in
      the region 415 to 490 nm as a result of illumination was observed on all the
      products. The effect was ascribed to photodegradation of riboflavin. Variation in
      two smaller peaks at approximately 620 nm and 630 nm was an interaction effect
      between exposure to light and air. A pronounced interaction effect between light
      and air produced intense blue fluorescence and off-flavors on Swiss-like
      Jarlsberg cheese. High correlations (0.83 to 0.93) between fluorescence spectra
      and sensory measured off-flavors were obtained for cream cheese. Results indicate
      that solid-sample fluorescence can be used as a nondestructive and rapid tool to
      measure the degree of light-induced degradation of riboflavin as well as sensory
      properties connected to storage of dairy products. Images of fluorescence can be
      used to visualize the intensity and propagation of this process. The simplicity
      and rapidity of the method offer rich opportunities for efficient evaluation of
      factors affecting light-induced oxidation in dairy products, such as packaging
      materials, light sources, exposure time, and temperature.

PMID- 12201520
TI  - Direct observation of bacterial exopolysaccharides in dairy products using
      confocal scanning laser microscopy.
AB  - The objective of this work was to develop a methodology for direct visualization
      of bacterial exopolysaccharides (EPS) in fully hydrated dairy products. The new
      method involved staining EPS with wheat germ agglutinin labeled with Alexa fluor
      488 or staining with concanavalin A 488. Samples were observed using confocal
      scanning laser microscopy. Distribution of EPS produced by Lactococcus lactis
      (CHCC 3367), a combination of Streptococcus thermophilus (CHCC 3534) and
      Lactobacillus delbrueckii ssp. bulgaricus (CHCC 769) and Lactobacillus
      delbrueckii ssp. bulgaricus RR in milk was compared in stirred and unstirred
      fermented milk. The EPS and proteins were observed as distinct entities, with EPS
      present in the protein network pores. EPS was observed in greater amounts in milk
      fermented by the ropy L. lactis culture than in milk fermented by the less ropy
      strain of S. thermophilus. Stirring the fermented milk caused aggregation of EPS
      into more extended structures. The more ropy the culture, the longer and larger
      the strands formed during stirring. The method was also applied to Feta cheese
      made with an EPS-producing strain of S. thermophilus. EPS was observed in the
      cheese as thick sheets filling pores in the protein network.

PMID- 12201522
TI  - A PCR-based method for the detection of Streptococcus agalactiae in milk.
AB  - Bovine mastitis caused by Streptococcus agalactiae is mainly subclinical and
      therefore can be diagnosed only in the laboratory. We developed a polymerase
      chain reaction (PCR)-based method for specific and sensitive detection of S.
      agalactiae in raw milk. The specificity of the PCR reaction is based on unique S.
      agalactiae DNA sequences within the 16S subunit of the rRNA genes. Two pairs of
      sequences were used as positive controls; general streptococci primers, which
      anneal to conserved areas within the 16S rRNA subunit gene, and primers, which
      anneal to sequences within bovine mitochondrial DNA. The method of detection
      includes selective enrichment of S. agalactiae in the milk sample, followed by
      DNA extraction using a rapid and simple procedure developed for this purpose, and
      specific PCR reaction with appropriate controls. The method enables the detection
      of one bacterium in 1 ml of raw milk. The method developed can be easily
      incorporated as part of routine screening of bulk milk collection tanks for early
      detection of infected cows in a herd.

PMID- 12201521
TI  - Adenoviral-mediated transfer of a lysostaphin gene into the goat mammary gland.
AB  - As a step toward preventing and curing Staphylococcus aureus mastitis, an
      adenoviral-mediated gene transfer technique was used to enable mammary cells to
      synthesize and secrete lysostaphin, an anti-staphylococcal protein. A lysostaphin
      gene, modified for eukaryotic expression of the bioactive variant, Gln125,232
      lysostaphin, was inserted into a replication deficient adenovirus by homologous
      recombination in 293 cells. The resulting adenoviral vector containing the
      modified lysostaphin gene (Ad-lys) was used to infect bovine mammary epithelial
      cells in vitro and caprine mammary cells in vivo. A similar adenoviral vector
      containing the Escherichia coli gene encoding beta-galactosidase (Ad-lacZ) was
      also evaluated. Transduction of cultured bovine cells by Ad-lacZ was confirmed by
      the presence of beta-galactosidase in fixed cells 48 h postinfection. Bovine
      cells transduced by Ad-lys secreted immunoreactive Gln125,232-lysostaphin (0.8
      microg/ml) into media that had approximately 20% bioactivity compared with native
      lysostaphin. To evaluate transduction in vivo, udder halves of four nonlactating
      goats were exposed to 10(10) plaque-forming units (pfu) ofAd-lacZ by two
      intramammary infusions given 48 h apart. The animals were euthanized 24 h later,
      and extensive expression of beta-galactosidase was detected in cells lining the
      teat canals, with more moderate expression observed in adjoining mammary
      parenchyma. Udder halves of two other nonlactating goats were infused with 10(10)
      pfu of Ad-lys while contralateral udder halves received Ad-lacZ. The animals were
      euthanized 48 h postinfusion. In both animals, extensive expression of beta
      galactosidase was detected in Ad-lacZ exposed teats. Immunoreative Gln125,232
      lysostaphin was detectable in secretions from Ad-lys exposed glands 24 h
      postinfusion, increasing to approximately 1 microg/ml at 48 h postinfusion. As
      with cultured bovine mammary epithelial cells, the bioactivity of goat-derived
      Gln125,232-lysostaphin was approximately 20% of native lysostaphin. These results
      demonstrate that an adenoviral vector can be used to introduce a gene into the
      ruminant mammary gland, enabling the secretion of a bioactive form of
      lysostaphin.

PMID- 12201523
TI  - Clinical responses to intramammary endotoxin infusion in dairy cows subjected to
      feed restriction.
AB  - Nonpregnant, midlactation primiparous Holstein cows were fed ad libitum (n = 12)
      or at 80% of maintenance energy requirements (n = 12) to determine whether feed
      restriction influences clinical response to endotoxin-induced mastitis. After 2
      wk of ad libitum or restricted feeding, one mammary quarter per cow was infused
      with 100 microg of endotoxin. Within 3 to 6 h of intramammary infusion, endotoxin
      increased mean rectal temperature, heart rate, and milk somatic cell count and
      immunoglobulin (IgG) concentration; and decreased blood leukocyte count and rumen
      motility in both restricted and ad libitum-fed cows. Mean serum and milk tumor
      necrosis factor-alpha (TNF-alpha) concentrations showed only modest increases
      following endotoxin infusion. Restricted fed cows had slightly different acute
      fever responses and significantly increased heart and respiration rates than ad
      libitum fed cows. However, feed restriction did not influence mean total
      leukocyte count, rumen motility, serum TNF-a concentrations or milk IgG and TNF
      alpha concentrations. Thus, results of this study suggest that energy balance
      does not significantly alter clinical symptoms following acute endotoxin-induced
      mastitis, at least in midlactation cows. As such, negative energy balance may not
      underlie the increases in severe coliform mastitis commonly observed in
      periparturient dairy cows.

PMID- 12201524
TI  - Comparative evaluation of SIMPL silicone implants and NIT natural teat inserts to
      keep the teat canal patent after surgery.
AB  - The objective of this study was the comparative evaluation of SIMPL silicone
      implants and NIT natural teat inserts to keep the teat canal patent after teat
      surgery. The study was performed on 100 teats of 97 cows treated surgically for
      milk flow disorders. After surgery, 53 teats were administered with SIMPL and 47
      with NIT, and rested for several days. Before treatment and 1 and 6 mo later
      quarter milk flow and milk yield were measured with Lactocorders; quarter milk
      was examined for somatic cell count (SCC), pathogens, and signs of mastitis (SCC
      > 100,000 and pathogens detected). Half a year after surgery milk flow, milk
      yield and SCC were equal from teats that had been inserted with SIMPL or NIT. The
      odds of detecting pathogens or signs of mastitis in the milk was lower in SIMPL
      than in NIT teats at this point in time. SIMPL teats stayed in the herd as long
      as NIT teats. Based on the results, it may be expected that teats inserted with a
      SIMPL or NIT do not differ long term in regards to milk flow, milk yield, SCC,
      and risk of removal from the herd. After the use of SIMPL, fewer pathogens may be
      detected in the milk long term than after the use of NIT.

PMID- 12201525
TI  - Propionibacteria fed to dairy cows: effects on energy balance, plasma metabolites
      and hormones, and reproduction.
AB  - To determine the effect of feeding Propionibacteria on energy balance, milk
      yield, and composition, metabolites and hormones of early-lactating dairy cows,
      multiparous Holstein cows were individually fed a total mixed ration from -2 to
      12 wk postpartum with no addition (control, n = 10) or with an additional 17 g of
      Propionibacteria culture daily (Treated, n = 9). Daily feed intake and milk
      production were recorded. Plasma cholesterol, nonesterified fatty acids (NEFA),
      leptin, insulin, glucose, insulin-like growth factor-I (IGF-I), IGF-binding
      proteins (IGFBP), and progesterone concentrations were measured up to twice
      weekly. Cows fed supplemental Propionibacteria had improved energy balance at wk
      1 of lactation and had lower DMI per kg of body weight than control cows on wk 3
      to 7, 10, and 12. Cows fed Propionibacteria had a greater percentage of milk
      protein and solids-not-fat and plasma NEFA concentrations than did control cows
      only at wk 1 of lactation. Treatment did not affect milk production or percentage
      of milk fat and lactose. Leptin levels were greater in treated than control cows
      throughout the study. Plasma glucose, insulin, cholesterol, IGFBP-3, and IGF-I
      concentrations were not affected by feeding Propionibacteria, but those variables
      increased with week postpartum. Plasma IGFBP-2 and IGFBP-5 levels decreased with
      week postpartum. Measures of reproductive and ovarian function did not differ
      between Propionibacteria-treated and control cows. Feeding Propionibacteria
      culture to transition and early lactating dairy cows may hold potential for
      improved milk protein production and metabolic efficiency during early lactation,
      without affecting reproductive function.

PMID- 12201526
TI  - Initiation of the breeding season in a grazing-based dairy by synchronization of
      ovulation.
AB  - Lactating dairy cows (n = 228) in a semiseasonal, grazing-based dairy were
      subjected to artificial insemination (AI) to start the 23-d breeding season (d 0
      to 22) followed by natural service (d 23 to 120). Cows were randomly assigned to:
      1) Ovsynch (GnRH, d -10; PGF2,, d -3; GnRH, d -1; timed AI, d 0) followed by AI
      at estrus (tail paint removal) on d 1 to 22 (Ovsynch; n = 114); or 2) AI at
      estrus (tail paint removal) throughout 23 d of AI breeding (tail paint; n = 114).
      Days to first AI service were greater and the 23-d AI service rate was less for
      tail paint vs. Ovsynch cows (12.0 +/- 0.6 d vs. 0 d; and 84.2 vs. 100%,
      respectively). However, conception to first AI was greater for tail paint vs.
      Ovsynch cows (47.3 vs. 27.3%, respectively). Cows in the tail paint group
      received only one AI, during 23 d of AI, but 46.4% of Ovsynch cows received a
      second AI, with similar conception (43.1%) to that of tail paint cows at first AI
      (47.3%). Based on serum progesterone, incomplete luteal regression after
      PGF2alpha, and poor ovulatory responses to GnRH contributed to lower conception
      to timed AI in the Ovsynch group. Cumulative pregnancy rates for tail paint and
      Ovsynch cows did not differ after 23 d of AI breeding (47.3 vs. 46.3%,
      respectively) nor after 120 d of AI/ natural service breeding (80.5 vs. 83.3%,
      respectively). Lactating cows in this grazing-based dairy synchronized poorly to
      Ovsynch resulting in reduced conception to timed AI compared with AI after tail
      paint removal.

PMID- 12201527
TI  - Short communication: milk fat response to low doses of tran-10, cis-12 conjugated
      linoleic acid (CLA).
AB  - Trans-10, cis-12 conjugated linoleic acid (CLA) is a potent inhibitor of milk fat
      synthesis. We examined the effect of low doses of trans-10, cis-12 CLA using
      Holstein cows in a 4 x 4 Latin square design. Milk yield and milk protein were
      unaffected, but abomasal infusion of 1.25, 2.5, and 5.0 g/d of trans-10, cis-12
      CLA reduced milk fat yield by 7, 16, and 29%, respectively. When combined with
      previous data, the reduction in milk fat yield was curvilinear, relating to both
      quantity infused and milk fat content of trans-10, cis-12 CLA (R2 = 0.99 and
      0.96, respectively). Further, changes in milk fatty acid composition indicated
      the mechanism involved inhibition of de novo fatty acid synthesis and the
      utilization of circulating fatty acids.

PMID- 12201528
TI  - Efficacy of carbohydrate sources for milk production by cows fed diets based on
      alfalfa silage.
AB  - The effectiveness of three carbohydrate sources, high-moisture ear corn (HMEC),
      cracked shelled corn (CSC), and a 50:50 mixture of HMEC plus dried citrus pulp
      (DCP), fed with or without supplemental rumen-undegraded protein as expeller
      soybean meal (ESBM), was assessed in 48 multiparous dairy cows. All diets
      contained (dry mater [DM] basis) 50% alfalfa silage, 10% ryegrass silage, 28%
      NDF, and one of six concentrates: A) 38% HMEC; B) 38% CSC; C) 19% DCP plus 19%
      HMEC; D) 27% HMEC plus 12% ESBM; E) 27% CSC plus 12% ESBM; or F) 13% DCP, 13%
      HMEC, and 12% ESBM. Diets A, B, and C averaged 19% crude protein, of which 53%
      was nonprotein nitrogen (NPN), and diets D, E, and F averaged 22% crude protein,
      of which 40% was NPN. Cows were fed a high-energy covariate diet for 2 wk,
      blocked into eight groups of six, based on covariate protein yield, then randomly
      assigned to diets that were fed for 12 wk. Feeding ESBM increased DM intake,
      yields of milk, fat-corrected milk, fat, protein, SNF, and milk and blood urea
      concentration and decreased weight loss. There were no production differences
      between HMEC and CSC. However, DM intake, yields of milk, fat-corrected milk,
      fat, protein, lactose, SNF, and milk SNF content all were lower on the diets
      containing DCP versus HMEC and CSC. A 6 x 6 Latin square trial conducted at the
      same time with six ruminally cannulated cows showed similar effects of diet on DM
      intake and milk production. Ruminal ammonia was elevated by ESBM but not ruminal
      total amino acids and branched-chain volatile fatty acids. Ruminal propionate was
      highest on HMEC diets and lowest on DCP diets; acetate, butyrate and acetate-to
      propionate ratio were lowest on HMEC diets and highest on DCP diets. These
      results indicated that, compared to HMEC and CSC, feeding the pectin-rich
      carbohydrate source DCP altered ruminal fermentation but depressed intake and
      milk production in lactating cows.

PMID- 12201529
TI  - Milk response to concentrate supplementation of high producing dairy cows grazing
      at two pasture allowances.
AB  - Twenty multiparous Holstein cows (four ruminally cannulated) in five 4 x 4 Latin
      squares with 21-d periods were used to study the effect of concentrate
      supplementation when grazed at two pasture allowances. The four dietary
      treatments resulted from the combination of two pasture allowance targets (low,
      25 vs. high, 40 kg of dry matter/cow per day) and two concentrate supplementation
      levels (zero vs. 1 kg of concentrate/4 kg of milk). Concentrate supplementation
      decreased pasture dry matter intake 2.0 kg/d at the low pasture allowance (17.5
      vs. 15.5 kg/d) and 4.4 kg/d at the high pasture allowance (20.5 vs. 16.1 kg/d).
      Substitution rate was lower at the low pasture allowance (0.26 kg pasture/kg
      concentrate) than at the high pasture allowance (0.55 kg of pasture/kg of
      concentrate). Total dry matter intake of both supplemented treatments averaged
      24.4 kg/d. Milk production of both supplemented treatments averaged 29.8 kg/d,
      but was increased with higher pasture allowance in the unsupplemented treatments
      (19.1 vs. 22.2 kg/d). Milk response to concentrate supplementation was 1.36 and
      0.96 kg of milk/kg of concentrate for the low and high pasture allowances,
      respectively. Concentrate supplementation reduced milk fat percentage but
      increased milk protein percentage. Rumen pH and NH3-N concentration were
      decreased with concentrate supplementation. Substitution rate was likely related
      to both negative associative effects in the rumen (reductions in rumen pH, rate
      of pasture digestion, and NDF digestibility) and reductions in grazing time. The
      latter was more important, quantitatively explaining at least 80% of the
      reduction in pasture dry matter intake observed.

PMID- 12201531
TI  - Technical note--a comparison of methods used to measure eating and ruminating
      activity in confined dairy cattle.
AB  - Detailed knowledge of chewing and rumination activities is critical to fully
      understand the dietary factors affecting normal rumen function. An automatic
      system for the digital recording of the jaw movements in free-ranging grazing
      cattle has been described, but its ability to measure chewing activity of cattle
      housed in confinement and fed total mixed rations has not yet been evaluated. The
      eating and ruminating behaviors of eight lactating dairy cows were recorded
      simultaneously by a wireless automatic system and by 5-min interval observation
      over 24-h periods. Results indicated that both methods agreed on identification
      of eating and ruminating bouts. Mean differences between methods for total time
      eating (8.7 min +/- 12.8) and ruminating (42.9 min +/- 12.0) were significantly
      different. The time recorded by observation in both eating and rumination was 3.6
      and 10.3% higher compared with the automatic system. Differences indicate
      inaccuracies in the observational method itself. The automatic system may prove
      useful in further studies examining eating and rumination activities in cattle.

PMID- 12201530
TI  - The effect of treating whole-plant barley with Lactobacillus buchneri 40788 on
      silage fermentation, aerobic stability, and nutritive value for dairy cows.
AB  - Chopped barley forage was ensiled untreated or treated with several doses (1 x
      10(5) to 1 x 10(6) cfu/g of fresh forage) of Lactobacillus buchneri 40788 in
      laboratory silos and untreated or treated (4 x 10(5) cfu/g) in a farm silo.
      Silage from the farm silos was fed to lactating cows. In the laboratory silo, the
      effects of inoculation on fermentation and aerobic stability were also compared
      to silage treated with a commercial inoculant and a buffered propionic acid
      additive. Inoculation with L. buchneri 40788 decreased the final concentrations
      of lactic acid but increased concentrations of acetic acid and ethanol in silage
      from laboratory and farm silos. Silages stored in laboratory silos did not heat
      after exposure to air for 7 d and were then mixed with alfalfa silage and a
      concentrate to form total mixed rations (TMR) that were further exposed to air.
      The TMR containing silages treated with L. buchneri 40788 or a buffered propionic
      acid-based additive took longer to heat and spoil than the TMR containing
      untreated silage or silagetreated with the commercial inoculant. Silage stored in
      a farm silo and treated with L. buchneri 40788 had fewer yeasts and molds than
      did untreated silage. Aerobic stability was greater in treated silage alone and
      in a TMR containing treated silage. Dry matter intake (18.6 kg/d), milk
      production (25.7 kg/d), and milk composition did not differ between cows fed a
      TMR containinguntreated or treated silage. These findings show that L. buchneri
      can improve the aerobic stability of barley silage in laboratory and farm silos
      and that feeding treated silage had no negative effect on intake or performance.

PMID- 12201532
TI  - Effects of abomasal vegetable oil infusion on splanchnic nutrient metabolism in
      lactating dairy cows.
AB  - Changes in the metabolism of nutrients by the portal-drained viscera (PDV) and
      liver may contribute to the reduction in dry matter intake (DMI) and other
      production responses generally observed in lactating dairy cows fed supplemental
      long-chain fatty acids (LCFA). In the present study, effects of a 7-d abomasal
      infusion of vegetable oil on arterial concentration and splanchnic (PDV and
      liver) metabolism of nutrients were measured in six cows at 55 (early lactation
      [ELAC]) and 111 (midlactation [MLAC]) d postpartum. Cows were fed for ad libitum
      DMI at 8-h intervals, and blood samples for measurement of splanchnic metabolism
      were obtained over 8 h beginning 2 h before feeding at 0830 h. Blood flow for the
      PDV and liver was increased by oil infusion and was greater in ELAC, despite
      similar-feed DMI during blood sampling. Increased blood flow in ELAC was
      associated with greater liver oxygen removal and glucose release that accompanied
      greater milk yield. In contrast, oil infusion had no effect on splanchnic oxygen
      use. Greater blood flow during oil infusion may have been due to specific effects
      of intestinal LCFA supply on PDV blood flow. Net PDV release and liver removal of
      branched-chain volatile fatty acids (VFA) and ammonia were increased by oil
      infusion. Net PDV release of longer-chain (4 and 5 C) VFA and NEFA was greater in
      ELAC, but net PDV flux of other nutrients was not affected by lactation stage,
      possibly due to the similarity of feed DMI. Oil infusion increased arterial
      concentration and net PDV release and liver removal of NEFA, and it decreased net
      liver release and arterial concentration of glucose. Effects of oil infusion on
      liver glucose release were associated with decreased daily DMI. In ELAC, arterial
      concentration and net liver removal of NEFA were also increased, but liver
      release of glucose was greater than in MLAC. Oil infusion and ELAC both increased
      net liver removal of L-lactate. The resulting decrease in net total splanchnic
      release of L-lactate in ELAC reflects decreased tissue energy balance of the
      cows. Generally, stage of lactation and relative milk yield had greater effects
      on metabolism of the liver than the PDV, in which metabolism was largely dictated
      by DMI. In the present study, there was little evidence to suggest an effect of
      stage of lactation on the metabolic response ofthe PDV and liver to postruminal
      LCFA supply.

PMID- 12201534
TI  - Relationship between content of crude protein in rations for dairy cows and milk
      yield, concentration of urea in milk and ammonia emissions.
AB  - During recent decades, efforts have been made in several countries to diminish
      the negative environmental influence of dairy production. The main focus has been
      on nitrogen and phosphorus. Modern dairy production in Western Europe is often
      based on imported feed-stuffs, mostly protein-rich feeds. In Sweden at least, it
      is wished that the use of imported feedstuffs in animal production will decrease
      due to the risk of contamination with Salmonella and the ban of using GMO crops
      in Swedish dairy production. An experiment was carried out to investigate whether
      a lower content of crude protein in the diet would decrease the ammonia release
      from cow manure and whether a well-balanced diet using only feedstuffs of Swedish
      origin would maintain milk production. Five treatments were arranged in a Latin
      square design. Two different protein supplements made of ingredients of Swedish
      origin were each fed at two protein levels, and a fifth imported commercial
      protein mix was fed at the higher level. The treatments with low protein levels
      (13.1 to 13.5%) had a significantly lower milk yield, kilograms of ECM, but, on
      the other hand the net profit, milk income minus feed cost was nearly the same in
      all treatments except diet C, which had lower feed cost but also lower net profit
      due to lower milk yield. The content of urea in milk was higher with diets high
      in crude protein (17%) content. A decreased protein level in the diets did not
      influence the content of casein or whey protein, but the commercial concentrate
      showed a tendency to give lower values than the Swedish mixtures. The low protein
      diets gave significantly lower ammonia release from manure compared with the high
      protein diets. There were no production differences between the diets of Swedish
      feeds compared with the imported control. The readily fermentable beet pulp
      should have helped cows use the higher N diet more efficiently and increased the
      response. This gives the rumen microbes a possibility to match the inflow of
      protein with carbohydrates. Income over feed costs shows that it is possible to
      compile diets using products of Swedish origin and still be competitive. On the
      other hand, this structure may change quickly due to altered world market prices.

PMID- 12201533
TI  - Effect of protein level in prepartum diets on metabolism and performance of dairy
      cows.
AB  - Multigravid Holstein cows (n = 75) were used in a randomized block design to
      evaluate the effect of prepartum diets formulated to supply surplus energy and
      incremental concentrations of protein on the nutritional status of dairy cows at
      parturition. Cows were blocked according to expected calving date and assigned to
      one of five diets: 9.7, 11.7, 13.7, 14.7, and 16.2% crude protein (CP). Dietary
      treatments were initiated 28 d before expected calving date and fed until
      parturition. A common diet was fed postpartum. Dry matter intake and milk yield
      were recorded daily through 90 d postpartum. Increasing the protein concentration
      from 9.7 to 14.7% of dry matter during the last 28 d of gestation improved
      responses of cows during lactation. Increasing dietary protein up to 14.7% also
      increased milk yield response to recombinant bovine somatotropin (rbST) during
      the ninth week of lactation and yields of 305-d 2x mature equivalent milk, milk
      protein, and milk fat. Plasma aspartate aminotransferase tended to be highest in
      cows fed 13.7 and 14.7% CP prepartum, but decreased linearly postpartum in
      response to dietary protein levels. There were no treatment differences for
      plasma insulin-like growth factor-1 (IGF-1) at d 60 postpartum (before rbST
      provision), but IGF-1 on d 90 (after rbST provision) was higher in plasma of cows
      fed 14.7% CP than the other diets except 13.7% CP. Close-up diets containing
      13.7% CP and surplus energy produced the most beneficial outcomes during the
      subsequent lactation.

PMID- 12201535
TI  - Variations in mammary metabolism during the natural filling of the udder with
      milk over a 12-h period between two milkings.
AB  - Two groups of four Holstein cows, one in their second and the other in their
      third or fourth lactation, were used to study temporal variations of mammary
      metabolism over a 12-h period between two milkings. Blood samples were collected
      every 30 min from an artery and a mammary vein during a 12-h interval between two
      milkings. Isoleucine, leucine, lysine, methionine, and phenylalanine mammary net
      fluxes varied or tended to change over time after milking with a similar pattern
      between whole blood and plasma. For these amino acids, whole blood and plasma net
      fluxes reached their maximum over the first 8 h after milking. Simultaneously,
      respiratory quotients decreased linearly and varied from 2.31 to 2.01 during the
      first 8 h of the period, suggesting active mammary lipogenesis. From 8 to 12 h
      after milking, mammary amino acid net fluxes decreased, while mammary oxygen
      uptake tended to increase with a concomitant decrease in the respiratory quotient
      reaching 1.84 to 1.40. These findings suggest that, beginning 8 h after milking,
      mammary uptake of amino acids starts to decrease and catabolic processes appear
      promoted; this phenomenon could help to explain the increase in milk production
      reported in the literature with increased milking frequency.

PMID- 12201536
TI  - The effect of zeolite A supplementation in the dry period on periparturient
      calcium, phosphorus, and magnesium homeostasis.
AB  - One potential way of preventing parturient hypocalcemia in the dairy cow is to
      feed dry cow rations very low in calcium (<20 g/d); but, because it is difficult
      to formulate rations sufficiently low in calcium, this principle has been almost
      abandoned. Recent studies have shown, however, that it is possible to prevent
      milk fever, as well as subclinical hypocalcemia, by supplementing the dry cow
      ration with sodium aluminium silicate (zeolite A), which has the capacity to bind
      calcium. The aim of this study was to further evaluate the effect, if any, of
      such supplementation on other blood constituents, feed intake, and milk
      production in the subsequent lactation. A total of 31 pregnant dry cows about to
      enter their third or later lactation were assigned as experimental or control
      cows according to parity and expected date of calving. The experimental cows
      received 1.4 kg of zeolite pellets per d (0.7 kg of pure zeolite A) for the last
      2 wk of pregnancy. Blood samples were drawn from all cows 1 wk before the
      expected date of calving, at calving, at d 1 and 2 after calving, and 1 wk after
      calving. Additionally, a urine sample was drawn 1 wk before the expected date of
      calving. Zeolite supplementation significantly increased the plasma calcium level
      on the day of calving, whereas plasma magnesium as well as inorganic phosphate
      was suppressed. Serum 1,25(OH)2D was significantly increased 1 wk before the
      expected date of calving among the experimental cows, whereas there was no
      difference in the urinary excretion of the bone metabolite deoxypyridinoline
      between the two groups. Feed intake was decreased among the zeolite-treated cows
      during the last 2 wk of pregnancy. No effect was observed on milk yield, milk
      fat, and milk protein in the subsequent lactation. The mechanisms and
      interactions involved in zeolite supplementation are discussed in relation to the
      observed improvement in parturient calcium homeostasis and to the observed
      depression in blood magnesium and inorganic phosphate.

PMID- 12201537
TI  - International dairy bull evaluations expressed on national, subglobal, and global
      scales.
AB  - Genetic evaluations on a global scale were calculated for Holstein bulls using
      the May 2001 International Bull Evaluation Service (Interbull) evaluations
      expressed on each of 27 national scales. National scale data were weighted by the
      country's proportion of total daughters from all bulls (population size) to
      represent market share. Correlations between Interbull evaluations on national
      scales and evaluations on a global scale ranged from 0.961 to 0.998 (mean of
      0.988). Number of top 100 bulls for protein yield that were in common between
      national and global scales ranged from 54 to 94 and was related significantly to
      mean genetic correlation between a country and the other 26 countries. Weighting
      of evaluations on national scales by population size, inverse of population size
      weight, or equal weight produced practically the same group of top bulls and
      correlations among the three global scales were 0.999. Thus, the method for
      combining Interbull evaluations expressed on national scales had only minor
      impact and was much less important than use of all data. Subglobal scales were
      established by a clustering technique that gave two to five groups. For grazing
      countries or other atypical systems, a subglobal scale may provide better
      guidance, although a scale representing three grazing countries did not provide
      the expected improvement over a global scale in the relationship with the three
      country scales. If conditions in non-participating countries are generally
      represented by participating countries, most needs are met by a global scale.

PMID- 12201538
TI  - Superiority of QTL-assisted selection in dairy cattle breeding schemes.
AB  - The superiority of selection schemes employing information about a known
      quantitative trait locus (QTL) over conventional schemes is examined for dairy
      cattle breeding schemes. Stochastic simulation of a dairy cattle population with
      selection practices, structures, and parameters similar to the US Holstein
      population was implemented. Additive genetic effects were estimated by an animal
      model. Two schemes were compared: a QTL-assisted selection scheme in which the
      genotype of a known QTL was accounted for in the animal model as a fixed factor,
      and a QTL-free selection scheme in which the QTL was simulated but was not fit
      separately in the animal model. Under the QTL-assisted selection scheme, all
      animals in the mixed model were assumed to be genotyped for the QTL. The effect
      of using QTL information on the genetic response, the frequency of the favorable
      QTL allele, and the accuracy of evaluation were examined. Moreover, the effect
      was studied in four distinct paths of selection: active sires, proven young
      bulls, bull dams, and first-lactation cows. Average superiority values of 4.6,
      7.6, 11.7, and 1.1% for genetic response were observed over 16 yr of selection
      for active sires, young bulls, bull dams, and first-lactation cows, respectively.
      Frequency of the favorable QTL allele changed faster in bull dams than males, and
      was the slowest in first-lactation cows. Finally, accuracy of evaluation under
      the QTL-assisted selection scheme was higher than under the QTL-free selection
      scheme. Young bulls ofthe QTL-assisted selection scheme on average had 0.049
      higher accuracy, and first-lactation cows had on average 0.185 higher accuracy
      than corresponding animals of the QTL-free selection scheme.

PMID- 12201539
TI  - Frequency and heritability of supernumerary teats in German simmental and German
      Brown Swiss cows.
AB  - The incidence of supernumerary teats has been recorded in 179,793 German
      Simmental and 37,460 German Brown Swiss cows. Data were collected from first-crop
      daughters of test bulls from 1987 to 1998. The number of sires was 4,298 and
      1,039, respectively. The average frequency of affected animals was 44.3% in
      German Simmental and 31.2% in German Brown Swiss. A significant yet small effect
      was found for herd-book membership (yes/no) and, in the Simmental data only, for
      inspector. The impact of year of birth and year of inspection was also
      significant, and more important, reflected a decrease of the population averages
      with time. Surprisingly, the incidence of supernumerary teats increased
      significantly with the parity number of dams in both breeds. A Bayesian threshold
      animal model approach was used to estimate the heritability of the occurrence of
      supernumerary teats. The posterior mean for the heritability was h2 = 0.45 in
      German Simmental and h2 = 0.43 in Brown Swiss, with standard errors of 0.01 and
      0.03, respectively. Ranks of sires obtained from threshold and linear models
      showed a rank correlation of roughly 0.8 in both breeds. For a sound
      identification of the worst sires, a threshold model is recommended.

PMID- 12201540
TI  - Polymorphism in the bovine growth hormone gene affects endocrine release in dairy
      calves.
AB  - The objective was to test whether calves with the Leu/Leu genotype release more
      growth hormone (GH) than calves with Leu/Val and Val/Val genotypes. Danish
      Holstein (n = 286), Danish Red (n = 68), and Danish Jersey (n = 61) calves were
      genotyped for the Leu/Val polymorphism in the GH gene and assessed for GH release
      following inducement by the growth hormone releasing hormone (GHRH). Three GH
      traits were assessed for each calf: BASELINE, PEAK, and RATE. BASELINE and PEAK
      are the mean concentration of GH in blood sampled before and after GHRH
      inducement. RATE is the disappearance rate of GH in blood sampled after GHRH
      inducement. Danish Jersey calves with Leu/Leu genotype had a higher PEAK and RATE
      than calves with the Val/Val genotype, whereas the Leu/Val genotype had an
      intermediate response. The contribution of the Leu/Val polymorphism to the total
      genetic variation of the BASELINE, PEAK, and RATE traits was 5, 30, and 27%,
      respectively. By contrast, the amount of GH released by the Danish Holstein and
      Danish Red calves was not influenced by their GH genotype. Further studies
      involving calves with all three genotypes are required to further elucidate
      whether this polymorphism has a functional role or whether it works through a
      linked-gene effect specific to certain cattle breeds.

PMID- 12201541
TI  - Ryegrass or alfalfa silage as the dietary forage for lactating dairy cows.
AB  - Renewed interest exists in using grass forages to dilute the higher crude protein
      (CP) and lower digestible fiber present in legumes fed to lactating dairy cows. A
      3 x 3 Latin square feeding study with 4-wk periods was conducted with 24 Holstein
      cows to compare ryegrass silage, either untreated control or macerated
      (intensively conditioned) before ensiling, with alfalfa silage as the sole
      dietary forage. Ryegrass silages averaged [dry matter (DM) basis] 18.4% CP, 50%
      neutral detergent fiber (NDF), and 10% indigestible acid detergent fiber (ADF)
      (control) and 16.6% CP, 51% NDF, and 12% indigestible ADF (macerated). Alfalfa
      silage was higher in CP (21.6%) and lower in NDF (44%) but higher in indigestible
      ADF (26%). A lower proportion of the total N in macerated ryegrass silage was
      present as nonprotein N than in control ryegrass and alfalfa silages. Diets were
      formulated to contain 41% DM from either rye-grass silage, or 51% DM from alfalfa
      silage, plus high moisture corn, and protein concentrates. Diets averaged 17.5%
      CP and 28 to 29% NDF. The shortfall in CP on ryegrass was made up by feeding 7.6%
      more soybean meal. Intake and milk yields were similar on control and macerated
      ryegrass; however, DM intake was 8.3 kg/d greater on the alfalfa diet. Moreover,
      feeding the alfalfa diet increased BW gain (0.48 kg/d) and yield of milk (6.1
      kg/d), FCM (6.8 kg/d), fat (0.26 kg/d), protein (0.25 kg/d), lactose (0.35 kg/d),
      and SNF (0.65 kg/d) versus the mean of the two ryegrass diets. Both DM efficiency
      (milk/DM intake) and N efficiency (milk-N/N-intake) were 27% greater, and
      apparent digestibility was 16% greater for DM and 53% greater for NDF and ADF, on
      the ryegrass diets. However, apparent digestibility of digestible ADF was greater
      on alfalfa (96%) than on ryegrass (average = 91%). Also, dietary energy content
      (estimated as net energy of lactation required for maintenance, milk yield, and
      weight gain) per unit of digested DM was similar for all three diets. Results of
      this trial indicated that, relative to ryegrass silage, feeding alfalfa silage
      stimulated much greater feed intake, which supported greater milk production.

PMID- 12201542
TI  - Educate hypertensive patients to increase compliance.

PMID- 12201543
TI  - Rating interest in clinical research among osteopathic medical students.

PMID- 12201544
TI  - The anatomy professor that ate New York: some dinosaurs are teachers, and some
      teach about dinosaurs.

PMID- 12201545
TI  - A retrospective study of cranial strain patterns in patients with idiopathic
      Parkinson's disease.
AB  - While providing osteopathic manipulative treatment to patients with Parkinson's
      disease at the clinic of the New York College of Osteopathic Medicine of New York
      Institute of Technology, physicians noted that these patients may exhibit
      particular cranial findings as a result of the disease. The purpose of this study
      was to compare the recorded observations of cranial strain patterns of patients
      with Parkinson's disease for the detection of common cranial findings. Records of
      cranial strain patterns from physician-recorded observations of 30 patients with
      idiopathic Parkinson's disease and 20 age-matched normal controls were compiled.
      This information was used to determine whether different physicians observed
      particular strain patterns in greater frequency between Parkinson's patients and
      controls. Patients with Parkinson's disease had a significantly higher frequency
      of bilateral occipitoatlantal compression (87% vs. 50%; P < .02) and bilateral
      occipitomastoid compression (40% vs. 10%; P < .05) compared with normal controls.
      Over subsequent visits and treatments, the frequency of both strain patterns were
      reduced significantly (occipitoatlantal compression, P < .01; occipitomastoid
      compression, P < .05) to levels found in the control group.

PMID- 12201546
TI  - Decreased laboratory testing for lecithin-to-sphingomyelin ratio and
      phosphatidylglycerol after fetal lung maturity assessment from lamellar body
      count in amniotic fluid.
AB  - The objectives of this study were to do inexpensive lamellar body count (LBC) in
      amniotic fluid, to do statistical analysis to evaluate cutoff values for fetal
      lung maturity (FLM) and fetal lung immaturity (FLI), to derive a threshold for
      obtaining a lecithin-to-sphingomyelin (L/S) ratio and phosphatidylglycerol
      percentage (%PG), and to determine the potential cost savings to the hospital if
      they use this new method. Testing (LBC, L/S ratio, and %PG) was done on 123
      specimens of amniotic fluid. Receiver operating characteristic (ROC) curve,
      discriminant, linear regression, chi2, and cost analyses were used to evaluate
      the laboratory and financial parameters. Lamellar body counts of greater than
      41,500 (Coulter MAXM: sensitivity, 90.5%; specificity, 87.7%; positive predictive
      value, 79.2%; negative predictive value, 94.7%) and greater than 32,000 (Coulter
      Gen.S: sensitivity, 90.5%; specificity, 85.2%; positive predictive value, 76.0%;
      negative predictive value, 94.5%) were the best threshold for biochemical FLM.
      Similarly, LBC of less than 24,000 (MAXM: sensitivity, 78.6%; specificity, 100%;
      positive predictive value, 100%; negative predictive value, 90.0%) and less than
      21,000 (Gen.S: sensitivity, 71.4%; specificity, 100%; positive predictive value,
      100%; negative predictive value, 87.1%) provided the best statistical cutoff for
      biochemical FLI from discriminant analysis. The authors concluded that FLM and
      FLI can be predicted with reasonable accuracy from LBC in amniotic fluid
      specimens. The expensive and not easily accessible L/S ratio and %PG can then be
      done only in cases in which LBC indicates transitional FLM. A cascade approach
      results in 86% savings to the hospital if the L/S ratio and %PG are not sent to a
      reference laboratory.

PMID- 12201547
TI  - Clinical experience with pneumococcal conjugate vaccines in infants and children.
AB  - Streptococcus pneumoniae is a leading cause of morbidity and mortality in
      pediatric patients, particularly in infants and children younger than 2 years.
      Each year, S pneumoniae is responsible for significant morbidity and mortality in
      the United States. During the past several decades, the emergence of penicillin
      nonsusceptible and multidrug-resistant pneumococcal isolates has become a major
      cause for concern, with the overuse or inappropriate use of antibiotics playing a
      significant role in the increase of resistance. Because the resistance of S
      pneumoniae to antibiotics has complicated the treatment of pneumococcal
      infections, attention has focused on the need to prevent disease through
      vaccination. The objective of this article is to describe the rationale for the
      development of pneumococcal conjugate vaccines and to summarize the clinical
      experience to date with these vaccines in infants and children.

PMID- 12201548
TI  - Title VII funding is associated with more family physicians and more physicians
      serving the underserved.
AB  - Title VII funding of departments of family medicine at U.S. medical schools is
      significantly associated with expansion of the primary care physician workforce
      and increased accessibility to physicians for the residents of rural and
      underserved areas. Title VII has been successful in achieving its stated goals
      and has had an important role in addressing U.S. physician workforce policy
      issues.

PMID- 12201549
TI  - Thrombolytic therapy vs. anticoagulation for PE.

PMID- 12201550
TI  - Vertebroplasty: weighing the benefits and the risks.

PMID- 12201551
TI  - Intracranial aneurysms: current evidence and clinical practice.
AB  - Unruptured intracranial aneurysms occur in up to 6 percent of the general
      population. Most persons with these aneurysms remain asymptomatic and are usually
      unaware of their presence. Risk factors for the formation of aneurysms include a
      family history of aneurysm, various inherited disorders, age greater than 50
      years, female gender, current cigarette smoking, and cocaine use. Because of the
      morbidity and mortality associated with surgical intervention, screening for
      aneurysms remains controversial. Two groups of patients may benefit from early
      detection: those with autosomal dominant polycystic kidney disease and those with
      a history of aneurysmal subarachnoid hemorrhage. These patients should undergo
      magnetic resonance angiography, followed by neurosurgical referral if an aneurysm
      is detected. Screening of patients who have two or more family members with
      intracranial aneurysms is controversial. Screening of patients who have one first
      degree relative with an aneurysm does not appear to be beneficial.

PMID- 12201552
TI  - Percutaneous vertebroplasty: new treatment for vertebral compression fractures.
AB  - Interventional radiologists have been performing image-guided spinal procedures
      for many years. Percutaneous vertebroplasty is a newer technique in which a
      medical grade cement is injected though a needle into a painful fractured
      vertebral body. This stabilizes the fracture, allowing most patients to
      discontinue or significantly decrease analgesics and resume normal activity. The
      impact of this procedure on the morbidity and expense associated with symptomatic
      osteoporotic vertebral compression fractures in the United States may be
      significant. Patients who are unresponsive to conservative therapy of bed rest,
      analgesics, and back bracing should be considered for vertebroplasty. This
      procedure is contraindicated in patients with active infection, untreated
      coagulopathy, and certain types of fracture morphology. Because many patients
      have multiple chronic fractures, there should be a strong correlation between the
      physical examination signs, symptoms, and cross-sectional imaging findings. The
      success rate for this procedure in treating osteoporotic fractures is 73 to 90
      percent. Vertebroplasty can effectively treat aggressive hemangiomas of the
      vertebral body and may be palliative in patients with malignant pathologic
      fractures. Significant complications of the procedure are less than 1 percent.

PMID- 12201553
TI  - Information from your family doctor. Vertebroplasty for spine fracture pain.

PMID- 12201554
TI  - Allergy testing.
AB  - Percutaneous and intradermal skin tests and laboratory assays of specific IgE
      antibodies may be useful in selected cases of allergy management. Percutaneous
      testing kits are available from various manufacturers. A number of common
      allergens are available in standardized preparations. Positive and negative skin
      controls are important in establishing reliable results. Antihistamine
      medications can interfere with skin testing and should be stopped beforehand.
      Serious reactions to skin testing are rare. Establishing the sensitivity and
      specificity of percutaneous testing is difficult because there is no widely
      accepted gold standard for defining a true allergic reaction. Intradermal testing
      is more sensitive than percutaneous methods but much less specific. Its use is
      restricted to testing for allergy to insect stings or penicillin. In cases where
      skin testing is not available or desirable, laboratory assays for IgE antibodies
      to specific allergens may be used. These assays are generally less sensitive than
      skin testing methods. Selected patients with allergic rhinitis or asthma that is
      not controlled with standard therapy may benefit from allergy testing, especially
      when it can target allergen avoidance measures or guide immunotherapy.

PMID- 12201555
TI  - Information from your family doctor. Allergy testing.

PMID- 12201556
TI  - Benefits and risks of psychiatric medications during pregnancy.
AB  - Traditionally, psychiatric medications were withheld during pregnancy because of
      fear of teratogenic and other effects. The emergence of evidence of the safety of
      most commonly used psychiatric medications, the availability of this information
      in the form of online databases, and the documentation of the adverse effects of
      untreated maternal mental illness have all increased the comfort of physicians
      and patients with respect to the use of psychiatric medications during pregnancy.
      The tricyclic antidepressants and fluoxetine (Prozac) appear to be free of
      teratogenic effects, and emerging data support similar safety profiles for the
      other selective serotonin reuptake inhibitors. The mood stabilizers appear to be
      teratogenic. With the exception of the known risk for depression to worsen in the
      postpartum period, there is little consistent evidence of the effects of
      pregnancy on the natural history of mental illness. Decisions regarding the use
      of psychiatric medications should be individualized, and the most important
      factor is usually the patient's level of functioning in the past when she was not
      taking medications.

PMID- 12201557
TI  - Information from your family doctor. Medicines for mental health during
      pregnancy.

PMID- 12201558
TI  - Tick removal.
AB  - Many methods of tick removal that have been reported in the literature have
      proved to be unsatisfactory in controlled studies. Some methods may even cause
      harm by inducing the tick to salivate and regurgitate into the host. Ticks are
      best removed as soon as possible, because the risk of disease transmission
      increases significantly after 24 hours of attachment. The use of a blunt, medium
      tipped, angled forceps offers the best results. Following tick removal, the bite
      area should be inspected carefully for any retained mouthparts, which should be
      excised. The area is then cleaned with antiseptic solution, and the patient is
      instructed to monitor for signs of local or systemic illness. Routine antibiotic
      prophylaxis following tick removal generally is not indicated but may be
      considered in pregnant patients or in areas endemic to tick-borne disease.

PMID- 12201559
TI  - Information from your family doctor. How to remove a tick.

PMID- 12201560
TI  - Screening for depression: recommendations and rationale.

PMID- 12201561
TI  - American Cancer Society issues 2002 guidelines for the early detection of cancer.

PMID- 12201562
TI  - Hypertensive intracerebral hemorrhage and brain edema.

PMID- 12201563
TI  - Surgical improvement of brain edema related to hypertensive intracerebral
      hemorrhage.
AB  - BACKGROUND: Patients with hypertensive intracerebral hemorrhage (ICH) are at risk
      for delayed neurological deterioration, especially during the second week after
      onset. Mass effect due to vasogenic edema caused by ICH has been shown to cause
      later deterioration. Control of brain edema and increased intracranial pressure
      (ICP) are related events that determine outcome. In this study, we compared the
      effects of three different treatments on brain edema caused by ICH. METHODS:
      Thirty-nine patients with ICH were involved in this study. Of these patients, 11
      had medical therapy (group A), 15 were treated with stereotactic aspiration plus
      local administration of urokinase (group B), and 13 underwent conventional
      craniotomy and hematoma removal (group C). The intracerebral hematoma volume on
      admission was measured on the the brain computed tomographs (CTs), and the
      cerebral edema volumes surrounding the hematoma were assessed with CT scans every
      5 to 7 days after symptom onset. RESULTS: The median intracerebral hematoma
      volumes were 23, 50 and 51 ml in groups A, B and C, respectively. Peak edema
      volume surrounding the hematoma was observed 5 to 15 days after symptom onset. A
      significant correlation (p < 0.05) was noted between peak edema and hematoma
      volumes in all groups. The ratio of median peak edema volume to median hematoma
      volume was 3.280 in group A, which was significantly higher than those in group B
      (0.745) and group C (0.863) (p < 0.05). CONCLUSIONS: The study revealed that
      brain edema induced by hypertensive ICH could be significantly ameliorated by
      surgical management. Stereotactic aspiration with local administration of
      urokinase was as effective as conventional craniotomy in reduction of brain edema
      volume caused by ICH and was characterized by its minimal invasiveness, easy
      performance, and safety.

PMID- 12201564
TI  - Is off-pump coronary artery bypass grafting in multivessel feasible.
AB  - BACKGROUND: "Off-pump" coronary artery bypass grafting (OPCABG) became more
      popular in recent years for its potential advantages of reducing perioperative
      morbidity related to cardiopulmonary bypass (CPB). We retrospectively analyzed
      the early results of multivessel OPCABG to compare them with conventional CABG
      under CPB. METHODS: From April 2000 to Oct 2000, 15 patients received multivessel
      OPCABG (group A). CTS or Octopus II stabilizer was used with coronary
      anastomosis. "Auto-perfusion system" was used at late stage of our series for
      myocardial protection in the procedure. At the same time, patients who received
      primary isolated CABG under CPB were compared as control (group B). RESULTS:
      There was no operative mortality or major morbidity in the group of multivessel
      OPCABG. Two patients who failed multivessel OPCABG due to hemodynamics compromise
      were converted to conventional CABG under CPB uneventfully. The amount of
      operative blood loss and donor blood transfusion, the duration of postoperative
      mechanical ventilation support, the mean intensive care unit stay and
      postoperative hospital stay were less in group A. CONCLUSIONS: Multivessel OPCABG
      is feasible in surgical techniques in selected patient. It is associated with
      minimal operative mortality and morbidity partly because of obviating the adverse
      effect of CPB. Prospective study with long-term follow-up is needed to better
      define the role of OPCABG.

PMID- 12201565
TI  - Non-stented pancreaticogastrostomy after pylorus-preserving
      pancreaticoduodenectomy.
AB  - BACKGROUND: We hypothesized that neutralization of the gastric acidity by
      alkaline pancreatic secretion via a non-stented pancreaticogastrostomy after
      pylorus-preserving pancreaticoduodenectomy (non-stented PPPD-PG) might provide
      protection against marginal or stress ulcer. Surgical risk of non-stented
      pancreaticogastrostomy was also assessed to clarify the importance of stenting in
      pancreatic anastomosis. METHODS: From January 1997 to December 2000, 54 patients
      with resectable periampullary lesions were included for non-stented PPPD-PG.
      Gastric pH and amylase levels were measured on the postoperative day 7. Surgical
      risks including pancreatic leakage, morbidity and mortality were also assessed.
      RESULTS: Patients undergoing the non-stented PPPD-PG presented significantly
      higher gastric levels of pH and amylase than healthy patients as controls (median
      pH 5.0 vs 2.8, p = 0.007; and median amylase 7,660 vs 21 IU/L, p = 0.031). Among
      the patients undergoing the non-stented PPPD-PG, low gastric pH and amylase
      levels were associated with high gastric drainage group > or = 600 c.c./day.
      However, only 1 of the 18 patients with low gastric amylase level (high gastric
      drainage group) developed significant steatorrhea and needed replacement of
      concentrated pancreatic enzymes. There were 18 (33.3%) complications and 1 (1.8%)
      mortality. The cause of death was cardiac arrythmia, not related to operation.
      Gastric atonia was the most common complication (18.5%), followed by wound
      infection, intraabdominal abscess, and intraabdominal bleeding in 2 patients
      (5.6%) individually. No pancreatic leakage or ulcer-related complication occurred
      after non-stented PPPD-PG. CONCLUSIONS: Experience of no pancreatic leakage in
      our 54 non-stented PPPD-PG implies that stenting of pancreaticogastrostomy might
      not be crucial in prevention of pancreatic leakage and ductal occlusion.
      Moreover, non-stented PPPD-PG can increase gastric pH and amylase levels, which
      might be beneficial in protection against marginal ulceration.

PMID- 12201566
TI  - A randomized, double-blind comparison of cerivastatin and lovastatin for
      treatment of primary hypercholesterolemia.
AB  - BACKGROUND: The efficacy and safety of the new statin, cerivastatin, in the
      Chinese patients with primary hypercholesterolemia remains to be determined.
      METHODS: In this prospective, double-blind, parallel-group study, patients with
      primary hypercholesterolemia were randomized to treatment with cerivastatin, 0.3
      mg (n = 21) or lovastatin, 20 mg (n = 22), for 8 weeks. The primary efficacy
      variable was percentage change of low-density lipoprotein (LDL) cholesterol from
      baseline. The secondary efficacy variables were percentage change of total
      cholesterol, triglycerides and high-density lipoprotein (HDL) cholesterol.
      RESULTS.:Both cerivastatin and lovastatin effectively reduced LDL cholesterol (
      33.2% vs. -29.3%, p = 0.63), total cholesterol (-25% vs. -20%, p = 0.10), and
      triglycerides (-21% vs. -14%,p = 0.27) (all p < 0.0001 for comparison with
      baseline), and slight increased HDL cholesterol (+2% vs. +8%, p = 0.008) over the
      8-week treatment period. The LDL cholesterol responsive rates according to the
      recommendations from the National Cholesterol Educational Panel (NCEP) were 43%
      and 32% for cerivastatin and lovastatin, respectively. The adverse event profiles
      of cerivastatin and lovastatin were similar. CONCLUSIONS: Cerivastatin 0.3 mg
      once daily is as effective and safe as lovastatin 20 mg once daily in lowering
      LDL and total cholesterol in Chinese patients with primary hypercholesterolemia.

PMID- 12201567
TI  - Obesity is the most important determinant of higher blood pressure among
      normotensive Chinese.
AB  - BACKGROUND: Higher blood pressure level in the normotensive range is a major
      predictor of the development of hypertension. The purpose of the present study
      was to investigate the risk factor profiles among different normotensive
      categories according to the Sixth Report of the Joint National Committee on
      Prevention, Detection, Evaluation and Treatment of High Blood Pressure (JNC VI).
      METHODS: This community-based survey was conducted in five counties of Kinmen
      from 1991 to 1995. We analyzed the data of fasting blood sugar, insulin, total
      and high-density lipoprotein cholesterol, triglyceride, blood urea nitrogen,
      creatinine, body mass index (BMI), and waist circumference from 6,372
      normotensive respondents (2511 men and 3861 women), who were categorized into
      three groups (High Normal, Normal, and Optimal) by JNC VI classification.
      RESULTS: By univariate analysis, significant differences among the groups were
      shown in fasting blood sugar, insulin, triglyceride, total cholesterol, BMI and
      waist circumference in both male and female population. By multiple stepwise
      logistic regression analysis, High Normal Group had significantly higher
      percentage of obesity (OR = 2.96, 95% CI = 1.77 4.13 in men; OR = 2.81, 95% CI =
      2.16 - 3.34 in women) than Optimal Group. Normal Group had more obesity (OR =
      2.01,95% CI = 1.09 - 3.70 in men; OR = 1.73, 95% CI = 1.31 - 2.30 in women) than
      Optimal Group, and High Normal Group had more obesity (OR = 1.81, 95% CI = 1.05 -
      2.92 in men; OR = 1.45,95% CI = 1.06 - 2.08 in women) than Normal Group.
      CONCLUSIONS: Normotensive subjects in the higher blood pressure categories had
      worse risk factor profiles. Obesity was the most important and consistent
      determinant of higher blood pressure categories.

PMID- 12201568
TI  - Gastrointestinal mucosal lesions in patients with acute pancreatitis.
AB  - BACKGROUND: Gastrointestinal mucosal lesion is frequently associated with major
      systemic disease, but its role in acute pancreatitis is rarely discussed. The aim
      of this study was to evaluate the incidence of ulcer formation of upper
      gastrointestinal (UGI) tract in patients with acute pancreatitis. METHODS: From
      May 1999 to April 2000, a total of 87 patients with acute pancreatitis who had
      received UGI endoscopy during hospitalization were included. Acute pancreatitis
      was diagnosed by typical epigastric pain with hyperamylasemia (> three times
      upper normal limit), hyperlipasemia, or abnormal finding of pancreas over
      abdominal sonography or computed tomography (CT). CT finding of acute
      pancreatitis was graded from A to E according to the system of Balthazar et al.
      According to the endoscopic findings, patients were subdivided into non-ulcer
      (normal and gastritis) and ulcer groups (esophageal, gastric, and/or duodenal
      ulcers). The correlations between the clinical features, CT grading, and
      endoscopic findings were analyzed. RESULTS: Of the 87 patients, 61 patients were
      male and 26 were female. The mean age was 55.1 +/- 18 years (range 19-87 years).
      The etiologies of pancreatitis include: gallstones (46), alcohol (20),
      hyperlipidemia (9) and idiopathic (12). Forty-six patients (52.9%) were found
      having ulcers by endoscopy (15 patients had previous ulcer history). The location
      of ulcers included esophagus (8), stomach (17) and duodenum (21). The incidence
      of ulcers was more frequent in patients with severe pancreatitis according to CT
      grading (A+B vs. C+D+E, p = 0.03). There was no statistical significance in
      relationship between ulcer formation and sex, age, etiologies, Ranson's score or
      clinical symptoms. CONCLUSIONS: More than half of patients with acute
      pancreatitis may complicate with upper gastrointestinal ulcers. The occurrence of
      ulcer was positively correlated with the severity of pancreatitis.

PMID- 12201569
TI  - The effect of codeine in anti-cough syrup on morphine screen.
AB  - BACKGROUND: Codeine is a lawfully permitted ingredient of over-the-counter cold
      and cough medicines readily available to the public in Taiwan. Drug abusers often
      use it as a substitute for morphine and heroin, attributing the morphine in the
      urine test to therapeutic cough medicine. In the literature, several criteria for
      taking codeine, using a single large-dose model, have been proposed. Here, we
      evaluate whether these criteria still fit in therapeutic situation. METHODS: Ten
      healthy volunteers each received, over two days, a total of 8 doses of cough
      syrup containing 4.5 mg of codeine phosphate per dose. Urine specimens were
      collected regularly during and in the 3 days after syrup consumption. The urine
      specimens were analyzed by an enzyme immunoassay screening test and a gas
      chromatography-mass spectrometry (GC-MS) confirmation test. RESULTS: Positive
      screen was noted during syrup use and 12-30 hours after the last dose of
      medication. The morphine:codeine ratio was < 1 during syrup use and 12 hour after
      the last dose of syrup. In only 1.4% of the urine specimens was the
      morphine:codeine ratio 1-3.0, and in these, the concentrations of morphine and
      codeine were both below 300 ng/mL. CONCLUSIONS: The results are compatible with
      the findings of the single large-dose model and may be used as a reference for
      the interpretation of urine analysis after the intake of multiple therapeutic
      doses of cough syrup with codeine.

PMID- 12201570
TI  - Hearing screening with portable screening pure-tone audiometer and distortion
      product otoacoustic emissions.
AB  - BACKGROUND: Hearing loss is a prevalent chronic problem among adults of all ages.
      Early identification and intervention for hearing loss will reduce the magnitude
      of functional disability. Hearing screening is an important item of physical
      examination. The purpose of this study is to evaluate the validity of hearing
      screening by means of the portable screening pure-tone audiometer and distortion
      product otoacoustic emissions (DPOAE) measurement. METHODS: This prospective
      study recruited 64 subjects visiting Taipei Veterans Hospital for physical
      examination. They underwent hearing tests performed with screening pure-tone
      audiometer, DPOAE and conventional pure-tone audiometer. The results of
      conventional pure-tone audiometry were used for "gold standards" and the normal
      auditory function was defined as the threshold less than or equal to 20 dB.
      Compared with the "gold standards," we used kappa statistic to assess the
      agreement of hearing results measured with screening pure-tone audiometer and
      DPOAE. RESULTS: For screening pure-tone audiometry, the kappa values at the 5
      tested frequencies (0.5, 1, 2, 4, 8 kHz) ranged from 0.79 to 0.93 and the
      agreement with the gold standards was classified as "excellent." The sensitivity,
      specificity and test accuracy values ranged from 91.8-98.5%, 88.0-96.3% and 89.8
      96.9%, respectively. For DPOAE measurement, the kappa values at the 3 tested
      frequencies (1, 2, 4 kHz) ranged from 0.62 to 0.78. The agreement was classified
      as "good" at 1, 4 kHz and "excellent" at 2 kHz. The sensitivity, specificity and
      test accuracy values ranged from 91.7-98.5%, 62.3-86.8% and 81.3-89.1%.
      CONCLUSIONS: We recommend a hearing screening measured at 0.5, 1, 2, 4, 8 kHz
      with screening pure-tone audiometer in a simple-type soundproof chamber and
      performed by a screening assistant. The DPOAE measurement may be used as an
      auxiliary tool to provide more information for early identification and
      differential diagnosis of hearing loss in clinical application.

PMID- 12201571
TI  - A rare synovial sarcoma of the kidney exhibiting translocation (X;18) and SYT
      SSX2 fusion gene.
AB  - Malignant spindle cell neoplasms are often a diagnostic challenge in
      histopathology, especially those arising from unusual locations. The authors
      report a primary synovial sarcoma of the kidney in a 19-year-old female.
      Initially, the tumor was considered adult Wilms' tumor exhibiting predominantly
      blastemal component. It was then revised to monophasic synovial sarcoma due to
      discovery of the characteristic chromosomal translocation (X;18)(p11.2;q11.2).
      This is the tenth reported case of renal synovial sarcoma with genetic
      confirmation. In addition to emphasizing the usefulness of genetic study in
      diagnostic pathology, the clinical implication of SYT/SSX subtypes and other
      additional chromosomal changes were also discussed by reviewing literature.

PMID- 12201572
TI  - Relationships between mefloquine blood levels, gender, and adverse reactions.

PMID- 12201573
TI  - Relationships between mefloquine blood levels, gender, and adverse reactions.

PMID- 12201574
TI  - Rickettsia rickettsii: as virulent as ever.

PMID- 12201575
TI  - Passive surveillance as an instrument to identify risk factors for fatal Rocky
      Mountain spotted fever: is there more to learn?
AB  - National surveillance for Rocky Mountain spotted fever (RMSF) dates from 1920;
      however, the collection of detailed epidemiologic, clinical, and laboratory data
      on RMSF by using case report forms began in 1970. Despite issues with compliance
      and changes in case definitions, surveillance data have permitted researchers to
      assess risk factors for fatal RMSF quantitatively. Factors consistently
      associated with increased risk of death include severity of disease, older age,
      lack of tick bite, absence of classic symptoms, delay in diagnosis and initiation
      of appropriate antibiotic treatment, and treatment with chloramphenicol only. In
      several studies, treatment with a tetracycline has been shown to be protective.
      The continuation of current passive surveillance activities may allow researchers
      to refine their estimates of risk but is unlikely to produce novel results.
      Modified surveillance activities could focus on evaluating the risk for fatal
      RMSF among special populations, monitoring appropriate antibiotic use, and
      assessing new diagnostic tests.

PMID- 12201576
TI  - Short report: Positive correlation between rosetting and parasitemia in
      Plasmodium falciparum clinical isolates.
AB  - Plasmodium falciparum isolates that form rosettes with uninfected red cells are
      associated with severe malaria in African children, although the mechanism by
      which rosetting contributes to severe disease is unknown. Here we have analyzed
      the relationship between rosetting and parasitemia in two samples of clinical
      isolates from children with malaria in Kilifi, Kenya. A consistent positive
      correlation was found between rosetting and parasitemia (Spearman's rank
      correlation coefficent p = 0.467, P < .001, n = 154, for 1993 study; p = .407, P
      < .001, n = 74, for 2000 study). Rosetting may enhance parasite growth and
      survival by facilitating invasion or promoting immune evasion, thus allowing
      higher parasitemia to develop and increasing the likelihood of severe malaria.

PMID- 12201577
TI  - Association of the IgG response to Plasmodium falciparum merozoite protein (C
      terminal 19 kD) with clinical immunity to malaria in the Brazilian Amazon region.
AB  - The antibody response to the C-terminal 19-kD fragment of Plasmodium falciparum
      merozoite surface protein-1 (PfMSP1-19) was investigated in groups of subjects
      living in areas of Brazil with different levels of malaria transmission. The
      prevalence and the levels of IgG to PfMSP1-19 increased with the time of exposure
      and were positively correlated with the absence of clinical symptoms in
      parasitemic patients. The frequency of positive response and the mean level of
      IgG were higher in areas where malaria prevalence was more intense, especially
      among asymptomatic patients. The serum absorbance values of the IgG1 isotype were
      significantly higher among subjects with long-term exposure and in asymptomatic
      infections. These data suggest a protective role of IgG1 in naturally acquired
      immunity in spite of the unstable transmission levels in the Brazilian Amazon.

PMID- 12201578
TI  - Evaluation of the pyrogenic threshold for Plasmodium falciparum malaria in naive
      individuals.
AB  - A retrospective statistical analysis of two independent data sets was undertaken
      to determine the peripheral Plasmodium falciparum parasitemia associated with the
      onset of fever in naive human hosts, and to assess the dynamics of this threshold
      during the course of the infection and subsequent reinfection. Analysis indicated
      that there were significant differences between the thresholds for different P.
      falciparum strains in one data set, and significant interactions between host
      ethnicity and parasite strain in the other. During untreated infections, the
      parasitemia associated with the onset of the second fever episode was
      significantly higher than that causing the first fever (P < 0.02). The
      parasitemia associated with the first fever episode of a reinfection was elevated
      relative to the threshold for the first fever episode of the initial infection;
      however, this difference reached statistical significance only in one of the data
      sets. These results provide further information on the pyrogenic threshold of
      malaria.

PMID- 12201579
TI  - In vitro chloroquine susceptibility and PCR analysis of pfcrt and pfmdr1
      polymorphisms in Plasmodium falciparum isolates from Senegal.
AB  - Chloroquine resistance has been linked to mutations in the pfcrt and pfmdr1 genes
      of Plasmodium falciparum. To estimate the prevalence of the pfcrt K76T, pfmdr1
      N86Y, and pfmdr1 D1246Y polymorphisms, isolates of P. falciparum from Senegal,
      West Africa, were analyzed, and the results were compared to in vitro chloroquine
      susceptibility. By the in vitro DELI test, 31% of these samples were resistant to
      chloroquine. Polymerase chain reaction-based assays and confirmatory sequencing
      demonstrated the pfcrt T76, pfmdr1 Y86, and pfmdr1 Y1246 alleles in 79%, 31%, and
      2% of the isolates, respectively. All three mutant alleles were present in both
      in vitro susceptible and resistant isolates. On the basis of these findings, it
      appears that these molecular markers are not consistently predictive of in vitro
      chloroquine resistance in Senegal.

PMID- 12201581
TI  - Polyclonal Plasmodium falciparum malaria in travelers and selection of antifolate
      mutations after proguanil prophylaxis.
AB  - The polymorphism of malaria parasites will greatly influence the efficiency of
      antimalarial drugs and vaccines. This study determined the genetic diversity of
      Plasmodium falciparum infections in 107 travelers and estimated the importance of
      mutations in the parasite dihydrofolate reductase (dhfr) gene for clinical
      breakthrough during proguanil prophylaxis. Genotyping with regards to the three
      highly polymorphic antigen-coding regions (merozoite surface protein-1 [msp-1],
      msp-2, and the glutamate-rich protein [glurp]) revealed multiple genotypes (up to
      five) in 64% of the patients. Single genotype infections were mainly associated
      with prior intake of antimalarial drugs, but also with a shorter stay in a
      malaria-endemic area and low parasite density. Malaria breakthrough despite
      proguanil prophylaxis was always associated with mutations in the dhfr gene;
      always the Asn-108 mutation and often the Ile-51 and Arg-59 mutations. The Leu
      164 mutation was found in four travelers from Africa. Travelers with limited time
      in an endemic area were often infected with polyclonal P. falciparum infections,
      which suggests that single mosquito inoculations are often composed of several
      genetically diverse parasites. Chemoprophylaxis reduces the number of infecting
      clones and selects for resistant parasites as shown for proguanil through
      mutations in the dhfr gene.

PMID- 12201580
TI  - Clinical and laboratory predictors of imported malaria in an outpatient setting:
      an aid to medical decision making in returning travelers with fever.
AB  - No evidence-based information exists to guide clinicians for giving presumptive
      treatment to returning travelers when malaria is strongly suspected on clinical
      grounds but laboratory confirmation is not immediately available or is negative.
      A prospective study was conducted in travelers or migrants who sought care for
      fever to identify clinical and laboratory predictors of Plasmodium parasitemia. A
      total of 336 questionnaires were collected (97 malaria case patients and 239
      controls). Multivariate regression analysis showed inadequate prophylaxis,
      sweating, no abdominal pain, temperature > or = 38 degrees C, poor general
      health, enlarged spleen, leucocytes < or = 10 x 10(3)/L, platelets < 150 x
      10(3)/L, hemoglobin < 12 g/dL, and eosinophils < or = 5% to be associated with
      parasitemia. Enlarged spleen had the highest positive likelihood ratio for a
      diagnosis of malaria (13.6), followed by thrombopenia (11.0). Posttest
      probabilities for malaria were 85% with enlarged spleen and 82% with
      thrombopenia. A rapid assessment can thus help to decide whether a presumptive
      treatment should be given or not, especially when the results of the
      parasitological examination are not immediately available or are uncertain.

PMID- 12201583
TI  - One year's experience with the polymerase chain reaction as a routine method for
      the diagnosis of imported malaria.
AB  - Given the problems encountered in westernized countries with the laboratory
      diagnosis of malaria, namely sensitivity of the conventional methods and
      detection of mixed infections, a polymerase chain reaction (PCR)-based diagnosis
      has been developed and routinely used. The PCR used two sets of primers to
      simultaneously detect any infection due to the genus Plasmodium, or to the
      species P. falciparum. The PCR results were available within six hours. Five
      hundred twenty-nine patients were tested, of whom 136 were found positive by the
      PCR, and only 104 by the quantitative buffy coat (QBC) method. The 32
      discrepancies were analyzed on the basis of the clinical data, and technical,
      molecular, and sequencing findings to ascertain the presence of Plasmodium DNA.
      The PCR-based diagnosis of malaria appeared to be a useful tool that was suitable
      as a second-line method when the results of conventional techniques were negative
      in patients presenting a syndromeconsistent with malaria, as well as yielding an
      accurate species identification.

PMID- 12201582
TI  - A retrospective examination of sporozoite-induced and trophozoite-induced
      infections with Plasmodium ovale: development of parasitologic and clinical
      immunity during primary infection.
AB  - A retrospective analysis was made of clinical and parasitologic parameters in
      patients with induced Plasmodium ovale infection to document the initial clinical
      and parasitologic response and their subsequent development of clinical and
      parasitologic immunity, and to determine the effect of previous homologous and
      heterologous malaria on subsequent infection with this parasite. The prepatent
      periods were relatively uniform. Eight patients injected with sporozoites that
      had been stored frozen had a median prepatent period of 14 days (range = 14-20
      days). Thirty-five patients infected via the bites of infected mosquitoes had a
      median prepatent period of 15 days (range = 12-18 days). In eight patients
      previously infected with P. vivax, the median prepatent period was 16 days. High
      intensity fever (> or = 104 degrees F) was frequently seen, with instances of
      fever > or = 106 degrees F recorded on many occasions. Fever > 101 degrees F and
      > 104 degrees F occurred for much shorter periods of time than had been observed
      in patients infected with P. falciparum. Parasite counts > 10,000/microL were
      infrequent; in most patients, such parasite counts rarely lasted more than two or
      three days. Gametocytemia was generally of low density and lasted only a few
      days. The overall length of the clinical and parasitologic period was much
      shorter compared with that seen in patients infected with P. falciparum. Previous
      infection with P. ovale did not prevent reinfection, but resulted in reduced
      levels of parasitemia and fever. Previous infection with heterologous species of
      Plasmodium did not prevent infection; some reduction in the frequency and
      intensity of fever and parasite counts was evident. Previous infection with
      homologous or heterologous parasites failed to eliminate the production of
      infective gametocytes. A total of 462 lots of mosquitoes were fed on 67 patients
      with no previous history of infection. Of these feedings, 168 (36.4%) resulted in
      infection as determined by the presence of oocysts on the midguts of dissected
      mosquitoes. As shown, the infection rate increased with the density of
      gametocytes even though 48 (23.4%) of 205 lots of mosquitoes fed when no
      gametocytes were detected were infected.

PMID- 12201584
TI  - Human leukocyte antigen class II control of the immune response to p126-derived
      amino terminal peptide from Plasmodium falciparum.
AB  - We investigated the relationships between class II human leukocyte antigens (HLA)
      and the antibody response to Plasmodium falciparum p126 protein and to its amino
      terminal portion (Nt47) in 2 malaria-endemic villages in Brazil, Colina and
      Ribeirinha. All people from the endemic areas had anti-p126 antibodies, and the
      frequencies of anti-Nt47 antibodies were similar in both communities (66% for
      Colina and 75% for Ribeirinha). Typing of HLA showed that Colina and Ribeirinha
      groups had no significant differences in HLA antigen frequencies. However, in
      both groups, significant associations between positive response to anti-Nt47 and
      presence of HLA-DR4, as well as between absence of response and presence of HLA
      DR15, were observed. The predominance of positive responses to Nt47 among HLA-DR4
      people was independent of the presence of any particular allele. There was no
      evidence for association between HLA-DQB1 alleles and antibody response to Nt47.
      Thus, naturally exposed people with different HLA class II antigens seem to
      respond differently to Nt47, indicating that the choice of relevant peptide
      sequences may have important consequences for subunit vaccine development.

PMID- 12201585
TI  - Neurotoxicity and efficacy of arteether related to its exposure times and
      exposure levels in rodents.
AB  - The neurotoxicity of beta-arteether (AE) is related to drug accumulation in blood
      due to slow and prolonged absorption from the intramuscular injection sites. In
      this efficacy and toxicity study of AE, the traditional sesame oil vehicle was
      replaced with cremophore to decrease the accumulation and toxicity of AE.
      Dihydroartemisinin (DQHS), a more toxic and active metabolite of AE, was also
      analyzed. When administered at a daily dosage of 25 mg/kg for seven days, blood
      accumulation of AE with sesame oil (AESO) was used had a 7.5-fold higher area
      under the curve (AUC) (on last versus first day dosing), while AE with cremophore
      (AECM) had only a 1.8-fold higher AUC. Although the accumulation of AECM was
      greatly reduced, its total exposure level (46.29 microg x h/ml) was 2.7-fold
      higher than with AESO (16.92 microg x h/ml) due to a higher bioavailability of
      AECM (74.5%) compared with AESO (20.3%). Total exposure time (calculated at over
      the minimal detected neurotoxicity level of 41.32 ng/ml) of AECM was 103 hours
      during the whole treatment period (192 hours), which was more than one-third
      (37%) less than with AESO (162 hours). Similar pharmacokinetic results were also
      shown with the active metabolite, DQHS. Anorexia and gastrointestinal toxicity
      with AESO were significantly more severe than with AECM (P < 0.001).
      Histopathologic examination of the brain demonstrated neurotoxic changes; the
      AESO rat group was significantly more severe than the AECM rat group. The brain
      injury scores with AECM were mild to moderate (2.3-3.0), and with AESO they were
      moderate to severe (3.0-4.7) on day 7 and day 10, respectively. In addition, the
      results of a 50% cure dose (CD50) against Plasmodium berghei in mice were 34.1
      mg/kg for AESO and 14.2 mg/kg for AECM, indicating a significant higher efficacy
      was found in the AECM animals. Toxicity and efficacy of DQHS were also dependent
      on its exposure time and level, which was the same as its parent drug (AE). In
      conclusion, following the seven-day treatment in rats, AE and DQHS exposure time
      and level varied based on the vehicle used. The extension of drug exposure time
      and the low peak level of AE and DQHS were more associated with severe
      neurotoxicity and lower antimalarial efficacy, whereas the high level and short
      exposure time of AE and DQHS resulted in higher efficacy and milder toxicity.

PMID- 12201586
TI  - Educational programs to enhance medical expertise in tropical diseases: the
      Gorgas Course experience 1996-2001.
AB  - In 1995, the American Society of Tropical Medicine and Hygiene (ASTMH) adopted
      defined criteria for accreditation of clinical training programs in tropical
      diseases. The first data on the development, enrollment, and outcomes of such a
      program are presented. A nine-week Diploma course, the Gorgas Course in Clinical
      Tropical Medicine, given on-site in the tropics (Lima, Cusco, and Iquitos, Peru)
      has trained 157 individuals from 38 countries from 1996 through 2001. The average
      age of participants was 38.3 with 11.3 years since graduation. Graduates were
      44.5% primary care physicians, 22.2% infectious diseases specialists, 12.7%
      emergency medicine specialists, 13.5% other specialists, and 7.1% nurses.
      Residents and fellows accounted for 32.8% and full-time academic faculty for
      11.0%. Approximately half of all eligible Gorgas graduates have taken the ASTMH
      certification examination. In response to the enrollees' profiles and needs,
      adult learning theory has been extensively used in course design. Stable
      professional relationships between multiple educational partners are required for
      an endeavor of this scope.

PMID- 12201587
TI  - Comparative safety and immunogenicity of two yellow fever 17D vaccines (ARILVAX
      and YF-VAX) in a phase III multicenter, double-blind clinical trial.
AB  - Yellow fever (YF) is a significant health problem in South America and Africa.
      Travelers to these areas require immunization. The United States, infested with
      Aedes aegypti mosquitoes, is at risk of introduction of this disease. There is
      only a single U.S. manufacturer of YF 17D vaccine, and supplies may be
      insufficient in an emergency. A randomized, double-blind outpatient study was
      conducted in 1,440 healthy individuals, half of whom received the U.S. vaccine
      (YF-VAX) and half the vaccine manufactured in the United Kingdom (ARILVAX). A
      randomly selected subset of approximately 310 individuals in each treatment group
      was tested for YF neutralizing antibodies 30 days after vaccination. The primary
      efficacy endpoint was the proportion of individuals who developed a log
      neutralization index (LNI) of 0.7 or higher. Seroconversion occurred in 98.6% of
      individuals in the ARILVAX group and 99.3% of those in the YF-VAX group.
      Statistically, ARILVAX was equivalent to YF-VAX (P = .001). Both vaccines
      elicited mean antibody responses well above the minimal level (LNI 0.7)
      protective against wild-type YF virus. The mean LNI in the YF-VAX group was
      higher (2.21) than in the ARILVAX group (2.06; P = .010) possibly because of the
      higher dose contained in YF-VAX. Male gender, Caucasian race, and smoking were
      associated with higher antibody responses. Both vaccines were well tolerated.
      Overall, the treatment groups were comparable with respect to safety except that
      individuals in the ARILVAX group experienced significantly less edema,
      inflammation, and pain at the injection site than those in the YF-VAX group. No
      serious adverse events were attributable to either vaccine. YF-VAX participants
      (71.9%) experienced one or more nonserious adverse events than ARILVAX
      individuals (65.3%; P = .008). The difference was due to a higher rate of
      injection site reactions in the YF-VAX group. Mild systemic reactions (headache,
      myalgia, malaise, asthenia) occurred in roughly 10% to 30% of participants during
      the first few days after vaccination, with no significant difference across
      treatment groups. Adverse events were less frequent in individuals with
      preexisting immunity to YF, indicating a relationship to virus replication.

PMID- 12201588
TI  - High levels of IgG4 to Schistosoma mansoni egg antigens in individuals with
      periportal fibrosis.
AB  - Specific IgG4 and IgE responses to adult worm antigen and soluble egg antigen
      (SEA) were examined in 267 individuals from an area in which schistosomiasis
      mansoni is endemic. Based on information obtained from clinical and sonographic
      examinations of this sample, the individuals were divided in three groups: 1) 204
      individuals without periportal fibrosis, and liver and spleen enlargements; 2) 41
      individuals without periportal fibrosis, but presenting with organopathy, with or
      without organomegaly; and 3) 22 individuals with periportal fibrosis, regardless
      of their status as having hepatomegaly and/or splenomegaly. Levels of IgG4 to SEA
      were significantly higher in sera from patients with fibrosis compared with the
      patients from the other two groups. We also found significantly higher levels of
      IgG4 against SEA in egg-negative patients with fibrosis compared with egg
      negative patients from the other two groups. This report demonstrates a specific
      humoral response in patients presenting with initial fibrosis, a form of
      schistosomiasis transient between intestinal and severe hepatosplenic.

PMID- 12201590
TI  - High prevalence of Brugia timori infection in the highland of Alor Island,
      Indonesia.
AB  - To identify areas endemic for Brugia timori infection, a field survey was carried
      out in 2001 on Alor, East Nusa Tenggara Timor, Indonesia. Elephantiasis was
      reported on this island by villagers as a major health problem. Bancroftian
      filariasis was detected in four villages in the coastal area, whereas B. timori
      was identified in four rice-farming villages. No mixed infections with both
      species were found. In the highland village Mainang (elevation = 880 m), 586
      individuals were examined for B. timori infection and 157 (27%) microfilaria
      carriers were detected. The prevalence of microfilaremic individuals standardized
      by sex and age was 25%. The geometric mean microfilarial density of
      microfilaremic individuals was 138 microfilariae/ml. Among teenagers and adults,
      males tended to have a higher microfilarial prevalence than females. Microfilaria
      prevalence increased with age and a maximum was observed in the fifth decade of
      life. In infected individuals, the microfilarial density increased rapidly and
      high levels were observed in those individuals 11-20 years old. The highest
      microfilaria density was found in a 27-year-old woman (6,028 microfilariae/ml).
      Brugia timori on Alor was nocturnally periodic, but in patients with high
      parasite loads, a small number of microfilariae was also detected in the day
      blood. The disease rate was high and many persons reported a history of acute
      filarial attacks. Seventy-seven (13%) individuals showed lymphedema of the leg
      that occasionally presented severe elephantiasis. No hydrocele or genital
      lymphedema were observed. This study showed that B. timori infection is not
      restricted to the lowland and indicated that it might have a wider distribution
      in the lesser Sunda archipelago than previously assumed.

PMID- 12201589
TI  - Bancroftian filariasis infection, disease, and specific antibody response
      patterns in a high and a low endemicity community in East Africa.
AB  - Bancroftian filariasis infection, disease and specific antibody response patterns
      in a high and a low endemicity community in East Africa were analyzed and
      compared to assess the relationship between these parameters and community
      transmission intensity. Overall prevalences of microfilaremia and circulating
      filarial antigenemia were 24.9% and 52.2% in the high and 2.7% and 16.5% in the
      low endemicity community, respectively. A positive history of acute attacks of
      adenolymphangitis was given by 12.2% and 7.1% of the populations, 4.0% and 0.9%
      of the adult (> or = 20 years old) individuals presented with limb lymphedema,
      and 25.3% and 5.3% of the adult males had hydrocele, in the high and the low
      endemicity community, respectively. Both infection and disease appeared earlier
      and reached much higher levels in the high than in the low endemicity community.
      The observed overall and age-specific infection and disease patterns in the two
      communities were in agreement with the view that these are primarily shaped by
      transmission intensity. No statistically significant relationships between
      infection status of fathers and mothers and that of their children were observed
      in any of the communities for either microfilaremia or for circulating filarial
      antigenemia. The overall levels (prevalence and geometric mean intensity) of
      filarial-specific IgG1, IgG2, IgG4, and IgE were significantly higher in the high
      endemicity community than in the low endemicity dommunity. Surprisingly, the
      opposite pattern was found for IgG3. Community transmission intensity thus
      appears to be an important determinant of observed inter-community variation in
      infection, disease, and host response patterns in Bancroftian filariasis.

PMID- 12201592
TI  - Case report: Ocular gnathostomiasis in northwestern Mexico.
AB  - A 42-year-old woman from Culiacan in the Sinaloa State of Mexico presented with a
      four-year history of migratory, pruritic, painful swellings of the face.
      Palpebral edema with conjunctival erythema developed when lesions developed near
      the eye. Routine eye examination showed a mobile worm in the anterior chamber.
      Following surgical removal, the parasite was identified by light and electron
      microscopy as an advanced third-stage larva of Gnathostoma sp. This prevalence of
      this helminthiasis may be increasing in areas where eating freshwater raw fish
      ("cebiche") is customary.

PMID- 12201591
TI  - Sensitive and specific serodiagnosis of onchocerciasis with recombinant hybrid
      proteins.
AB  - Onchocerciasis remains a major health hazard in many tropical countries. However,
      the existing tools for diagnosis of the disease have limitations, particularly
      regarding the detection of low level or early infections. To design an optimized
      reagent, we exploited the high antibody reactivity of patient sera against the
      Onchocerca volvulus proteins Ov20 and Ov33, which have been described as highly
      sensitive and specific immunodiagnostic reagents for producing hybrid proteins.
      The construct OvH2 was composed of Ov20 fused to Ov33, while OvH3 consisted of
      the C-terminus of Ov20 linked to Ov33. When these constructs were tested with
      sera from patients with onchocerciasis and control sera, OvH2 showed a
      sensitivity of 98.5% and a specificity of 97.7% and OvH3 showed a sensitivity of
      98.5% and a specificity of 95.35%. All non-responders were from Ecuador. These
      results surpass those of existing single recombinant antigens, suggesting that
      our hybrid proteins combined the sensitivity of the two parent proteins. Tests
      based on OvH2 should prove suitable for monitoring onchocerciasis control
      programs and individual diagnosis.

PMID- 12201593
TI  - The perforation problem in hydatid disease.
AB  - Hydatidosis (echinococcosis) is endemic in the Mediterranean region, including
      Turkey. We evaluated the problem of perforation in hydatidosis. The clinical data
      on 21 patients with intra-abdominal hydatid cyst perforation who were treated in
      the last 10 years were evaluated retrospectively. Twelve patients (57%) were men
      and nine (43%) were women. Their average age was 40 (range = 20-65). Blunt trauma
      was the etiologic mechanism in four cases (19%). Except for a case with a cyst in
      the left inguinal region, most (95%) of the patients had primary hepatic
      hydatidosis (95%). The procedures used on the 30 cysts found in 21 patients were
      as follows: partial cystectomy and drainage in 21 (70%), total cystectomy in 5
      (17%), partial cystectomy plus omentopexy in 2 (7%), and drainage plus vacuum
      obliteration in 2 (7%). The average postoperative hospital stay was 12 days
      (range = 6-30). Two patients (10%) had complications: an incisional hernia
      developed in one patient, and a gastrocutaneous fistula developed in the other.
      Albendazole (10 mg/kg/day) was prescribed for two months. The mean follow-up time
      was 80 months (range = 6-131). Three patients (14%) underwent additional surgery
      for recurrence at various times. The morbidity and mortality associated with
      perforated hydatid cysts were higher when compared with that of nonperforated
      cysts. Hydatidosis is endemic in Turkey and traffic accidents are common. When
      these factors coexist, hydatid perforation should be considered in trauma
      patients with stable hemodynamics, but suspicious abdominal findings. The choice
      of the operative approach should be based on the experience of the surgeon and
      regional characteristics.

PMID- 12201594
TI  - Epidemiology of amebiasis in a region of high incidence of amebic liver abscess
      in central Vietnam.
AB  - The recent identification of Entamoeba dispar as a separate species, which is
      nonpathogenic for humans but morphologically indistinguishable from Entamoeba
      histolytica, has prompted the World Health Organization to recommend reinforced
      efforts for reassessment of the epidemiology of amebiasis and, in particular, of
      E. histolytica. In this regard, the distribution of amebic liver abscess (ALA)
      cases were analyzed in the province of Thua Thien Hue (TT Hue) in central
      Vietnam, a region known for its high incidence of invasive amebiasis. In
      addition, in a particular area of Hue City, a parasitologic and seroepidemiologic
      survey was performed to identify possible risk factors for transmission of E.
      histolytica. Based on the analysis of hospital charts from April 1990 to April
      1998, 2,031 cases of ALA were identified, indicating an ALA incidence of at least
      21 per 100,000 inhabitants per year. Incidence varied substantially between the
      various districts of TT Hue and directly correlated with population density. The
      risk for ALA was significantly higher in summer and was age and sex dependent
      because 95% of the cases were adults, of which more than 80% were males. There
      was no clustering of cases within households and recurrent cases of ALA occured
      more frequently than predicted in the study population. Despite the higher
      incidence of ALA in males, the parasitologic and seroepidemiologic survey
      revealed a significant higher infection rate for intestinal protozoon parasites,
      including E. histolytica in females. Besides level of education and access to a
      toilet or tapwater, use of river water was identified as an important risk factor
      for E. histolytica infection.

PMID- 12201595
TI  - Diarrhea prevention through household-level water disinfection and safe storage
      in Zambia.
AB  - A water quality intervention that consists of water treatment, safe storage, and
      community education was field tested in Kitwe, Zambia. A total of 166
      intervention households were randomly selected from one community and 94 control
      households from another. Baseline surveys were conducted and the intervention was
      distributed. Weekly active diarrhea surveillance, biweekly water testing, and a
      follow-up survey were conducted. Compliance was high in intervention households:
      97% reported using disinfectant and 72-95% had measurable chlorine in their water
      in biweekly testing. The percentage of intervention households storing water
      safely increased from 41.5% to 89.2%. Stored water in intervention households was
      significantly less contaminated with Escherichia coli than water in control
      households (P < 0.001). Diarrheal disease risk for individuals in intervention
      households was 48% lower than for controls (95% confidence interval = 0.3, 0.9).
      This intervention is a useful tool for preventing waterborne diseases in families
      in developing countries who lack access to potable water.

PMID- 12201597
TI  - Large genetic distances among Aedes aegypti populations along the South Pacific
      coast of Mexico.
AB  - A population genetic analysis was conducted among 20 Aedes aegypti collections
      from 19 cities along the south Pacific coast in the Mexican states of Guerrero,
      Oaxaca, and Chiapas and in Coatepeque, Guatemala. Genetic variation was scored at
      131 random amplified polymorphic DNA loci. The amount of genetic differentiation
      among collections was approximately 3 times as great as detected among
      collections in an earlier study in northeastern Mexico. Regression analysis of
      linear or road distances on linearized F(ST) indicated that collections are
      genetically isolated by distance. Cluster analysis failed to group collections in
      geographic proximity, and there was as much genetic variation among collections
      60 km apart as there was among all collections (approximately 900-km range). The
      large genetic differentiation in southern Mexico reflects reduced gene flow among
      mosquitoes arising in a greater diversity of habitats and altitudes than exists
      among northeastern collections. It is likely that dispersal via human commerce in
      the northeast confounds patterns of natural gene flow.

PMID- 12201596
TI  - Early childhood diarrhea is associated with diminished cognitive function 4 to 7
      years later in children in a northeast Brazilian shantytown.
AB  - Diarrhea is well recognized as a leading cause of childhood mortality and
      morbidity in developing countries; however, possible long-term cognitive deficits
      from heavy diarrhea burdens in early childhood remain poorly defined. To assess
      the potential long-term impact of early childhood diarrhea (in the first 2 years
      of life) on cognitive function in later childhood, we studied the cognitive
      function of a cohort of children in an urban Brazilian shantytown with a high
      incidence of early childhood diarrhea. Forty-six children (age range, 6-10 years)
      with complete diarrhea surveillance during their first 2 years of life were given
      a battery of five cognitive tests. Test of Non-Verbal Intelligence-III (TONI)
      scores were inversely correlated with early childhood diarrhea (P = .01), even
      when controlling for maternal education, duration of breast-feeding, and early
      childhood helminthiasis (Ascaris or Trichuris). Furthermore, Wechsler
      Intelligence Scale for Children (WISC-III) Coding Tasks and WISC-III Digit Span
      (reverse and total) scores were also significantly lower in the 17 children with
      a history of early childhood persistent diarrhea (PD; P < .05), even when
      controlling for helminths and maternal education. No correlations were seen
      between diarrhea rates and Wide Range Assessment of Memory and Learning subtests
      or WISC-III Mazes. This report (with larger numbers of participants and new
      tests) confirms and substantially extends previous pilot studies, showing that
      long-term cognitive deficits are associated with early childhood diarrhea. These
      findings have important implications for the importance of interventions that may
      reduce early childhood diarrheal illnesses or their consequences.

PMID- 12201598
TI  - Identification of mosquito avian-derived blood meals by polymerase chain reaction
      heteroduplex analysis.
AB  - A polymerase chain reaction (PCR) heteroduplex assay (HDA) was developed to
      identify avian derived mosquito blood meals to the species level. The assay used
      primers amplifying a fragment of the cytochrome B gene from vertebrate but not
      invertebrate species. In Culex tarsalis fed on quail, PCR products derived from
      the quail cytochrome B gene were detected seven days post-engorgement. In an
      analysis of wild-caught mosquitoes, 85% of blood-fed mosquitoes produced
      detectable PCR products. Heteroduplex patterns obtained from bird-derived PCR
      products were found to permit the unambiguous identification of all species
      examined. No intraspecific variation in HDA patterns was found. The PCR-HDA was
      used to characterize blood meals in wild caught Cx. tarsalis. Of the 67 blood
      meals analyzed, 60% were derived from avian sources. Of the avian blood meals,
      65% were derived from a single host, the common grackle.

PMID- 12201600
TI  - An OspA-based genospecies identification of Lyme disease spirochetes (Borrelia
      burgdorferi) isolated in Taiwan.
AB  - To further identify the genospecies of Lyme disease spirochetes (Borrelia
      burgdorferi) isolated in Taiwan, we analyzed the genomic identities of these
      Taiwan isolates (TWKM1-7) by genospecies-specific polymerase chain reaction (PCR)
      assay, restriction fragment length polymorphism (RFLP) analysis, and gene
      sequencing based on the OspA gene sequences of B. burgdorferi sensu lato. PCR
      analysis indicates that all of these Taiwan isolates were genetically related to
      the genospecies of B. burgdorferi sensu stricto by their differential
      reactivities with genospecies-specific PCR primers. After cleavage by DraI, three
      different RFLP patterns in relation to three different genospecies of Lyme
      disease spirochetes were observed, and all of these Taiwan isolates were
      affiliated with the genospecies of B. burgdorferi sensu stricto. The phylogenetic
      analysis also reveals that the sequence similarity of PCR-amplified OspA gene of
      these Taiwan isolates is highly homogeneous, with a homogeneity of more than
      99.8% within the genospecies of B. burgdorferi sensu stricto. These results
      confirm that the genomic identities of these Taiwan isolates belong to the
      genospecies of B. burgdorferi sensu stricto.

PMID- 12201599
TI  - Population-based case-control investigation of risk factors for leptospirosis
      during an urban epidemic.
AB  - Between March and October 2000, 157 suspected cases of leptospirosis hospitalized
      with complications of Weil's syndrome and a mortality of 8% were identified in
      Salvador, Brazil. We conducted a population-based case-control study to identify
      risk factors for acquisition of leptospirosis in neighborhoods with high
      endemicity during the rainy season-associated urban epidemic. Sixty-six (65%) of
      101 laboratory-confirmed cases and 125 age and sex-matched healthy neighborhood
      controls were interviewed. Residence in proximity to an open sewer (matched odds
      ratio [OR] = 5.15, 95% confidence interval [CI] = 1.80-14.74), peri-domiciliary
      sighting of rats (OR = 4.49, 95% CI = 1.57-12.83), sighting groups of five or
      more rats (OR = 3.90, 95% CI = 1.35-11.27), and workplace exposure to
      contaminated environmental sources (OR = 3.71, 95% CI = 1.35-10.17) were found to
      be independent risk factors for acquiring disease. Some of these risk factors are
      amenable to focused interventions, which include provision of closed drainage
      systems for sewage and reduction of rodent populations in the peri-domicilary
      environment. Environmental control of transmission may help to greatly reduce the
      incidence of severe leptospirosis.

PMID- 12201602
TI  - Genetic and ecologic characteristics of Bartonella communities in rodents in
      southern China.
AB  - Ecologic and bacteriologic observations of small mammals captured in Yunnan
      Province in the People's Republic of China indicated that Bartonella infections
      occurred at a high prevalence among some rodent species. Sequence analyses of the
      citrate synthase genes of these Bartonella demonstrated that rodents in this
      region harbored a diverse assemblage of strains. The Bartonella isolates obtained
      from Apodemus, Eothenomys, and Rattus typically clustered separately by genus of
      rodent host. Cultures obtained from Rattus rats were genetically related to
      Bartonella elizabethae, a recognized human pathogen. The finding of Bartonella
      species in a high proportion of the rodent samples from Yunnan suggests the need
      to investigate whether these agents might be responsible for cases of febrile
      illnesses of unknown etiology in southern China and elsewhere in southeastern
      Asia.

PMID- 12201601
TI  - Chemotactic migration of the Lyme disease spirochete (Borrelia burgdorferi) to
      salivary gland extracts of vector ticks.
AB  - The migration of Lyme disease spirochetes (Borrelia burgdorferi) toward salivary
      gland extracts (SGEs) of vector ticks was determined by a modified U-tube
      chemotaxis assay. Responses of cultured spirochetes to the SGEs were measured by
      dark-field microscopy at intervals after the initial inoculation. The average
      numbers of spirochetes that migrated were compared between U-tubes containing
      either SGEs or phosphate-buffered saline (PBS). Spirochetes showed increased
      migration in tubes containing SGE, and migration was approximately 10-20-fold
      higher than that for spirochetes observed in tubes containing PBS. In addition,
      the span of migration showed no significant difference relative to the origin of
      spirochete isolation. These results demonstrate that spirochete migration can be
      enhanced by SGEs from fed vector ticks. This mechanism may contribute to the
      novel transmission of Lyme disease spirochetes between cofeeding infected and
      uninfected ticks in nature.

PMID- 12201603
TI  - Age-specific prevalence of antibodies to hepatitis A in Santiago, Chile: risk
      factors and shift in age of infection among children and young adults.
AB  - Transition from high to lower endemicity of hepatitis A virus (HAV) infection may
      portend increased public health burden with the shift of infection to older ages
      and increasing morbidity and mortality. This report describes age-specific
      prevalence of antibodies to HAV (anti-HAV) among children and young adults in
      Santiago, Chile, compared with previous prevalence data and assesses factors
      predictive for anti-HAV. In 1998, a serosurvey was performed in Metropolitan
      Santiago, designed to enroll a representative, age-stratified population on the
      basis of area of residence. A total of 784 individuals (age range, 1-24 years)
      were enrolled. Anti-HAV prevalence by year of life was as follows: ages 1 to 4,
      12.5%; 5 to 9, 26.2%; 10 to 14, 43.4%; 15 to 19, 57.4%; 20 to 24, 73.9%.
      Adjusting for age, factors associated (inversely) with anti-HAV included
      residential areas of higher socioeconomic status (SES), parental education, and
      household characteristics of potable water, municipal sewage system, and the
      presence of a toilet or refrigerator in the house. In logistic regression
      analysis, only maternal years of education and residence in areas of higher SES
      remained independently associated with anti-HAV. Excluding those from higher SES
      areas, comparison of the age-specific anti-HAV prevalence data from previous
      studies of similar methodology in areas of lower SES revealed consistent
      decreases across all age groups; the age-standardized prevalence for this age
      range (1-24 years) dropped from 53.7% in 1990 to 40.6% in 1998. In light of the
      growing pool of susceptible individuals at older ages, with HAV continuing to
      circulate in the communities, evaluation of the feasibility of vaccination
      programs would be judicious.

PMID- 12201604
TI  - Hepatitis c in a community in Upper Egypt: risk factors for infection.
AB  - This investigation's objective was to identify risk factors for hepatitis C virus
      (HCV) in a village in Upper Egypt with a moderately high prevalence (8.7%) of
      antibodies to HCV (anti-HCV). A representative sample of 6,012 (63%) of the 9,581
      village inhabitants was included in the study. A questionnaire solicited
      information regarding risk factors for infection, and blood samples were tested
      for anti-HCV. Parenteral risks identified in age-adjusted analysis included blood
      transfusions, dental procedures, hospital admission, surgery, complicated
      deliveries, history of injection therapy for schistosomiasis, and history of
      frequent injections. Circumcision was pervasive and was not associated per se
      with ant-HCV; however, circumcision by an informal, rather than formal, health
      care provider was associated with anti-HCV among young men and boys. The results
      did not reveal any unique community-acquired exposures that caused HCV
      infections: inhabitants who had tattoos, who smoked goza, who were shaved by a
      community barber, or who had their ears pierced were not at greater risk for anti
      HCV than those who did not. Risks identified in multivariate analysis for both
      those older and younger than 30 years included prior parenteral therapy for
      schistosomiasis and blood transfusion; for those 30 or younger, circumcision by
      an informal rather than formal health care provider, and frequent injections; and
      for those older than 30, never attending college, invasive medical procedures,
      and complicated deliveries. Selecting for those with blood transfusion, prior
      parenteral therapy for schistosomiasis, and invasive medical procedures would
      identify less than half of those infected. Inclusion of frequent injections would
      identify 80% of those infected with HCV, but as a result of the pervasive use of
      injections, it would not discriminate from those uninfected. Nonetheless, general
      reduction of these exposures and assuring sterile practices are logical goals for
      intervention.

PMID- 12201605
TI  - Unrecognized HIV infection, risk behaviors, and perceptions of risk among young
      black men who have sex with men--six U.S. cities, 1994-1998.
AB  - The incidence of human immunodeficiency virus (HIV) infection among young black
      men who have sex with men (BMSM) is among the highest of all risk groups in the
      United States. Two important strategies to reduce HIV transmission among young
      BMSM are to increase the proportion of men who are aware of their HIV infection
      and to increase the consistent use of condoms among sexually active men. However,
      limited information is available to help develop HIV-testing and condom-promotion
      programs for young BMSM. To address this need, data from CDC's Young Men's Survey
      (YMS) were used to evaluate the prevalence of unrecognized HIV infection,
      barriers to testing, and reasons for nonuse of condoms among BMSM aged 15-22
      years. This report summarizes the results of the survey, which indicated that of
      the 16% of young BMSM participants who were infected with HIV, nearly all were
      unaware of their infection. Few young BMSM reported testing frequently for HIV,
      and many reported engaging in behaviors that could transmit HIV because they
      perceived themselves or their partners to be at low risk for infection. These
      findings underscore the urgency of expanding and improving prevention efforts for
      young BMSM by increasing the demand for and availability of HIV-testing services
      and by providing high-quality prevention counseling that includes assessment and
      clarification of perceived risks for infection.

PMID- 12201606
TI  - Nonfatal sports- and recreation-related injuries treated in emergency departments
      -United States, July 2000-June 2001.
AB  - Each year in the United States, an estimated 30 million children and adolescents
      participate in organized sports, and approximately 150 million adults participate
      in some type of nonwork-related physical activity. Engaging in these activities
      has numerous health benefits but involves a risk for injury. CDC analyzed data
      from the National Electronic Injury Surveillance System All Injury Program (NEISS
      AIP) to characterize sports- and recreation-related injuries among the U.S.
      population. This report summarizes the results of that analysis, which indicate
      that during July 2000-June 2001 an estimated 4.3 million nonfatal sports- and
      recreation-related injuries were treated in U.S. hospital emergency departments
      (EDs). Injury rates varied by sex and age and were highest for boys aged 10-14
      years. Effective prevention strategies, including those tailored to specific
      activities and those aimed at children, adolescents, and adults, are needed to
      reduce sports- and recreation-related injuries in the United States.

PMID- 12201607
TI  - Delayed diagnosis of fragile X syndrome--United States, 1990-1999.
AB  - Fragile X syndrome (FXS) is the leading cause of inherited mental retardation,
      affecting approximately 50,000 persons in the United States. FXS occurs when a
      mutation on the X chromosome is passed from mother to child. Preliminary data
      suggest that children affected by FXS experience a delay in diagnosis, a pattern
      common to other single-gene disorders. The molecular test used to definitively
      diagnose FXS became available in 1991. The first indication of FXS within a
      family is usually the diagnosis of FXS in a child. Although no proven treatments
      exist for FXS, prompt diagnosis enables children to receive early intervention
      services and families to receive genetic counseling. To assess the timing of a
      diagnosis of FXS in an affected child and genetic counseling for the family, the
      Frank Porter Graham Child Development Institute (University of North Carolina at
      Chapel Hill) conducted a survey during August-October 2001 of 140 parents whose
      first child affected by FXS was born and had the condition diagnosed during 1990
      1999. This report summarizes the results of that survey, which indicate that
      approximately half of the families did not learn the diagnosis for more than a
      year after first concerns about their child's development or behavior, and half
      reported having subsequent pregnancies before FXS was diagnosed in their first
      child. These findings emphasize the importance of increased opportunities for
      early diagnosis so children and families can receive all possible benefits,
      including genetic counseling and intervention services.

PMID- 12201609
TI  - Replication and construct validation of the Barrow Neurological Institute Screen
      for Higher Cerebral Function with a Swedish population.
AB  - A Swedish translation of the Barrow Neurological Institute Screen for Higher
      Cerebral Functions was administered to 52 normal control subjects and 36 patients
      with well-documented brain dysfunction. Findings replicated those reported in
      American samples. Level of performance was strikingly similar between Swedish
      controls and American controls, especially in individuals between 15 and 39
      years. Swedish patients with brain dysfunction performed at levels significantly
      below the Swedish control subjects. The sensitivity of the test was 83%
      (correctly classifying 30 of 36 patients); patients with a higher level of
      education were misclassified. The present study replicates earlier findings and
      adds to the construct validity of the Barrow Neurological Institute Screen. This
      test may also prove useful for studying rehabilitation outcomes in Swedish
      patients.

PMID- 12201610
TI  - Awareness of deficits in stroke rehabilitation.
AB  - The aim of this study was to evaluate the awareness of deficit profiles of stroke
      patients undergoing rehabilitation, and examine the impact of unawareness on
      rehabilitation functional outcomes. Sixty first-event stroke patients, 36 after
      right hemisphere damage and 24 after left hemispheric damage were included. The
      Awareness Interview was administered at admission to rehabilitation, and
      patients' responses were compared with standardized cognitive and neurological
      evaluations. The FIM motor scale and a safety rating were used to measure
      functional outcomes at discharge from rehabilitation and at 1-year follow up. The
      frequency of unawareness for motor and sensory deficits was low, whereas
      unawareness of cognitive deficits was much higher. Unawareness was not associated
      with a specific lesion site, however a significant association was found with
      cortical involvement, and with lesion size. In the right hemispheric damage group
      a significant negative correlation was found between total unawareness scores and
      discharge functional outcomes. Multiple regression revealed that unawareness at
      admission was a significant predictor of discharge FIM motor scores in the right
      hemispheric damage group, beyond the contribution of cognitive and demographic
      variables. Findings delineate the multifaceted nature of unawareness phenomenon,
      and highlight the significance of unawareness in post-stroke rehabilitation.

PMID- 12201611
TI  - Long-term pain conditions after a stroke.
AB  - The aim of this study was to classify and describe the characteristics of
      different long-term pain conditions after a stroke by clinical examination and
      pain assessment using the Pain-O-Meter and a Pain questionnaire. Pain was
      classified as central post-stroke pain (n = 15), nociceptive pain (n = 18), and
      tension-type headache (n = 10). In 65%, pain onset was within 1-6 months and the
      pain intensity revealed individual differences. Many pain descriptors was common,
      some were discriminating as burning in central and cramping in nociceptive pain,
      and pressing and worrying in headache. More than half with central or nociceptive
      pain had continuous or almost continuous pain. Cold was the factor mostly
      increasing the pain in central, physical movements in nociceptive pain, and
      stress and anxiety in headache. More than one-third had no pain treatment and two
      thirds of those with central pain had no or inadequate prescribed pain treatment.
      The clinical findings support the classification of pain and describe
      discriminating and common pain characteristics in pain conditions after a stroke.

PMID- 12201612
TI  - External power output changes during prolonged cycling with electrical
      stimulation.
AB  - This study analysed external power output and physiologic responses in 5
      individuals with paraplegia during 40 minutes of electrical stimulation leg cycle
      exercise. Cycling was performed on a motor-driven isokinetic ergometer that
      enabled precise determinations of power output. Electrical stimulation was
      increased to 120-140 mA within the first 5 minutes and remained constant
      thereafter. Power output increased to 10.7 +/- 3.0 W after 2 minutes, dropped to
      5.3 +/- 1.8 W after 6 minutes and subsequently recovered to 8.2 +/- 2.2 and 6.1
      +/- 2.3 W after 19.5 and 40 minutes, respectively. Oxygen consumption increased
      to 0.47 +/- 0.09 l/min after 6 minutes and declined during the second half of the
      exercise bout. Gross mechanical efficiency after 19.5 minutes was elevated
      compared with the value after 6 minutes. Heart rate was significantly increased
      at the end of the trial. The time-dependent variability of power output and
      physiological responses question the concept of steady state for this form of
      exercise.

PMID- 12201613
TI  - Clinical tests on impairment level related to low back pain: a study of test
      reliability.
AB  - The objectives of the study were, in a working population, to standardize and
      evaluate a set of clinical tests on impairment level related to the low back with
      reference to intra- and inter-rater reliability. The study was undertaken in two
      steps. In step 1, 15 tests were examined for inter-rater reliability by three
      pairs of physiotherapists and for intra-rater reliability by one physiotherapist.
      Intra-rater reliability was acceptable (kappa > 0.40) for 14 of the 15 tests.
      Inter-rater reliability was acceptable for 7 of the 15 tests. In step 2, the
      tests, indicating a non-acceptable inter-rater reliability (kappa < 0.40) were
      further standardized and retested by two of the physiotherapists. This further
      standardization procedure resulted in an acceptable inter-rater reliability for
      all of these tests. Clinical tests of a working population should preferably be
      performed by the same rater. However, when tests are performed by different
      raters, it is suggested that test procedures should be regularly standardized,
      and in pain provocation tests, the magnitude of the applied pressure should be
      checked regularly and compared with co-raters, in order to improve inter-rater
      reliability.

PMID- 12201614
TI  - A randomized clinical trial comparing general exercise, McKenzie treatment and a
      control group in patients with neck pain.
AB  - Seventy-seven patients with neck pain in the primary health care were included in
      a prospective, randomized clinical trial and randomly assigned to general
      exercise, McKenzie treatment, or a control group. Seventy patients completed the
      treatment; response rate 93% at 12-month follow-up. All three groups showed
      significant improvement regarding the main outcomes, pain intensity and Neck
      Disability Index, even at 12-month follow-up, but there was no significant
      difference between the groups. In all, 79% reported that they were better or
      completely restored after treatment, although 51% reported constant/daily pain.
      In the McKenzie group compared with the control group, a tendency toward greater
      improvement was noted for pain intensity at 3 weeks and at 6-month follow-up, and
      for post-treatment Neck Disability Index. Significant improvement in Distress and
      Risk Assessment Method scores was shown in the McKenzie group only. The three
      groups had similar recurrence rates, although after 12 months the McKenzie group
      showed a tendency toward fewer visits for additional health care. The study did
      not provide a definite evidence of treatment efficacy in patients with neck pain,
      however, there was a tendency toward a better outcome with the two active
      alternatives compared with the control group.

PMID- 12201615
TI  - Group training in a pool causes ripples on the water: experiences by persons with
      late effects of polio.
AB  - The purpose of the present qualitative study was to describe how persons with
      late effects of polio experienced dynamic exercise in water in a group. Semi
      structured interviews with 15 participants were carried out and analysed
      according to the phenomenographic approach. The results showed great variation in
      the way the participants experienced the group training. Fourteen different
      categories appeared focusing on three different aspects: the self, the training
      situation and the world around. It appears that the experienced effect of group
      training in water goes beyond improving physical functions.

PMID- 12201616
TI  - Treatment of overactive bladder with once-daily extended-release tolterodine or
      oxybutynin: the antimuscarinic clinical effectiveness trial (ACET).
AB  - Treatment with the antimuscarinic agents tolterodine and oxybutynin is the
      mainstay of therapy for overactive bladder, a chronic and debilitating condition
      characterized by urinary urgency with or without urge incontinence, usually in
      combination with urinary frequency and nocturia. This study consisted of two
      trials; in one, patients with overactive bladder were randomized to 8 weeks of
      open-label treatment with either 2 mg or 4 mg of once-daily extended-release
      tolterodine (TER), and in the other to 5 mg or 10 mg of extended-release
      oxybutynin (OER). The study protocol and design were identical for the two trials
      and site selection ensured that there was no bias in either trial for the
      tendency of investigators to prescribe one drug rather than the other, or for
      geographical location. A total of 1289 patients were enrolled, 669 in the
      tolterodine trial (TER 2 mg, n = 333; TER 4 mg, n = 336) and 620 in the
      oxybutynin trial (OER 5 mg, n = 313; OER 10 mg, n = 307). Fewer patients
      prematurely withdrew from the trial in the TER 4 mg group (12%) than either the
      OER 5 mg (19%; p = 0.01) or OER 10 mg groups (21%; p = 0.002). More patients in
      the OER 10 mg group than the TER 4 mg group withdrew because of poor tolerability
      (13% vs 6%; p = 0.001). After 8 weeks, 70% of patients in the TER 4 mg group
      perceived an improved bladder condition, compared with 60% in the TER 2 mg group,
      59% in the OER 5 mg group and 60% in the OER 10 mg group (all p < 0.01 vs TER 4
      mg). Response to therapy was greater in a subgroup of patients whose perception
      of bladder condition was moderate to severe at baseline (TER 4 mg 77% vs OER 10
      mg 65%; p < 0.01). Dry mouth was dose-dependent with both agents, although
      differences between doses only reached statistical significance in the oxybutynin
      trial (OER 5 mg vs OER 10 mg; p = 0.05). Patients treated with TER 4 mg reported
      a significantly lower severity of dry mouth compared with OER 10 mg. In
      conclusion, the greater efficacy and tolerability of tolterodine ER 4 mg suggests
      improved clinical effectiveness compared with oxybutynin ER 10 mg.

PMID- 12201617
TI  - Intraoperative sentinel lymph node examination by imprint cytology during breast
      surgery.
AB  - BACKGROUND: Sentinel lymph nodes (SLNs) predict the axillary status and may allow
      lymphadenectomy on a selective basis. The aim of this study was to assess the
      accuracy of intraoperative imprint cytology (IC) analysis of sentinel nodes in
      patients with early breast cancer. METHODS: A total of 128 SLNs from 87 cases
      that had been identified with Patent blue dye were bisected for hematoxylin and
      eosin stained touch preparations. Intraoperative evaluation of sentinel node
      involvement by IC was compared with the final histopathological results of
      permanent sections. Tumour-negative nodes in standard paraffin sections were
      further studied using an anticytokeratin antibody (CK-IHC). RESULTS: Thirty-six
      of all SLNs contained metastases in paraffin sections, of which 32 were detected
      by IC procedure (sensitivity 88.8%). Three sentinel nodes were tumour-positive on
      imprint cytology and tumour-negative on stained paraffin sections. Comparison of
      the results of the imprints with the final histology (H&E and CK-IHC) showed a
      sensitivity of 83.3% and a negative predictive value of 92.5%. The specificity
      and positive predictive value were 100%. CONCLUSION: Touch imprint cytology is a
      simple and quick method of intraoperative screening of SLNs for the presence of
      metastases in patients with breast cancer. Results may be improved by an
      appropriate enlargement of the surface sampled and the use of rapid CK-IHC on the
      touch preparations.

PMID- 12201618
TI  - Effects of a fixed mixture of 25% insulin lispro and 75% NPL on plasma glucose
      during and after moderate physical exercise in patients with type 2 diabetes.
AB  - OBJECTIVE: To compare the plasma glucose (PG) response with a fixed mixture of
      25% insulin lispro and 75% NPL (Mix25), prior to a meal and 3 h before exercise,
      to human insulin 30/70 (30/70) in patients with type 2 diabetes. RESEARCH DESIGN
      AND METHODS: Thirty-seven patients were treated in a randomized, open-label, 8
      week, two-period crossover study. Mix25 was injected 5 min before breakfast and
      dinner throughout the study, as was 30/70 on inpatient test days and on
      outpatient dose titration days. Following the 4-week outpatient phase, patients
      were hospitalized, and exercised at a heart rate of 120 beats/min on a cycle
      ergometer two times for 30 min, separated by 30 min rest, starting 3 h after a
      339 kcal breakfast. RESULTS: The 2-h postprandial PG was significantly lower with
      Mix25 ((mean +/- SEM) 10.5 +/- 0.4 mmol/l vs 11.6 +/- 0.4 mmol/l; p = 0.016).
      Maximum decrease in PG from onset of exercise to end of exercise was
      significantly less with Mix25 (-3.6 +/- 0.29 mmol/l vs -4.7 +/- 0.31 mmol/l; p =
      0.001). The maximum decrease in PG over 6 h, after exercise onset, was
      significantly less with Mix25 (-4.3 +/- 0.4 mmol/l vs -5.9 +/- 0.4 mmol/l; p <
      0.001). The frequency of hypoglycemia (blood glucose (BG) < 3 mmol/l or symptoms)
      during the inpatient test was not different between treatments. During the
      outpatient phase, the frequency of patient-recorded hypoglycemia was
      significantly lower with Mix25 (0.7 +/- 0.2 episodes/30 d vs 1.2 +/- 0.3
      episodes/30 d; p = 0.042). CONCLUSIONS: Mix25 resulted in better postprandial PG
      control without an increase in exercise-induced hypoglycemia. The smaller
      decrease in PG during the postprandial phase after exercise may suggest a lower
      risk of exercise-induced hypoglycemia with Mix25 than with human insulin 30/70,
      especially for patients in tight glycemic control.

PMID- 12201619
TI  - Efficacy and acceptability of fusafungine, a local treatment for both nose and
      throat infections, in adult patients with upper respiratory tract infections.
AB  - The objective of this study was to assess the effectiveness and acceptability of
      fusafungine in the treatment of patients with community-acquired, upper
      respiratory tract infections. These infections, although frequently of viral
      origin, may be conducive to bacterial superinfection. Fusafungine, a combination
      of several enniatins, has been shown to display bacteriostatic activity against
      many micro-organisms responsible for infections of the respiratory tract, along
      with anti-inflammatory activity. This open, multi-centre study analysed data on
      166 patients suffering from upper respiratory tract infections treated for 7 or
      10 days with a fusafungine metered-dose spray. The incidence of upper respiratory
      tract symptoms was significantly reduced from baseline (p < or = 0.001) with the
      treatment evaluated as excellent or good by 92.1% of physicians. In 77.7% of the
      patients, no further treatment was necessary at the end of the seven-day
      therapeutic period. Out of the 37 patients who had the treatment prolonged for
      three more days, 78.4% had regression of their URTI at the end of therapy. In
      terms of tolerability, assessment by the investigators and the patients
      themselves demonstrated that fusafungine was extremely well tolerated.
      Acceptability of the treatment was considered poor by only one patient. Results
      of this study suggest that fusafungine, whatever the aetiology of the infection,
      gives rapid relief of nasal and pharyngeal symptoms and provides strong evidence
      of its efficacy and acceptability in treating URTIs.

PMID- 12201620
TI  - Switching antipsychotic medications: general recommendations and switching to
      amisulpride.
AB  - As more and more novel antipsychotic agents are introduced, the need for
      practical guidelines on switching these medications is becoming increasingly
      important. Indications for a switch include situations where the patient or his
      family/caregiver requests a change in medication, where the patient cannot
      tolerate current treatment, where they have comorbid physical or psychiatric
      conditions or where they have achieved only a partial remission, are refractory
      to treatment or have relapsed. Cross-tapering is generally the most acceptable
      method of switching, although abrupt withdrawal may be necessary in some cases,
      such as when a patient develops a severe or acute reaction to their current
      treatment. Possible problems of switching include the risk of discontinuation
      reactions and the re-emergence of psychotic symptoms. The pharmacological profile
      of amisulpride means it has a relatively low potential for interactions with
      other drugs and may be started while discontinuing the previous antipsychotic. It
      should be started at the target dose for the patient's current symptoms. A
      retrospective questionnaire among 60 patients switching to amisulpride treatment
      was undertaken to identify the characteristics of patients switching
      antipsychotics and their reasons. Patients were switched from a variety of
      antipsychotic medications, both traditional (42% of patients) and atypical (58%).
      Most patients (87%) had at least two reasons for changing medication, with lack
      of efficacy, adverse events and treatment optimisation before reintegration being
      the most common. Contrary to recommendations, 89% of patients were switched
      abruptly between medications. A total of 62% of patients received amisulpride
      doses in the range 400-800 mg/day and most (72%) required no dose adjustment. The
      great majority of patients (87%) switched to amisulpride without problems.

PMID- 12201621
TI  - Choosing the right dopamine agonist for patients with Parkinson's disease.
AB  - Dopamine receptor agonists (DA) are assuming an increasing importance in the
      treatment of both early and advanced symptoms of Parkinson's disease (PD).
      However, choosing the right DA for patients with PD unfortunately remains more a
      pragmatic medical art than a science. The aim of this review is to provide a
      realistic point of view on the strengths and weaknesses of five DAs:
      bromocriptine, ropinirole, pergolide, pramipexole and piribedil. This has been
      done by analysing their respective: (1) flexibility in PD, i.e. in monotherapy,
      in early and in late combination with levodopa; (2) safety profile and (3)
      titration schedule. These five DAs are not evenly matched regarding these three
      criteria. The differences observed highlight the therapeutic value of piribedil,
      which has a flexible indication, adapted to all stages of PD, a safer profile and
      the most simple initiation schedule.

PMID- 12201622
TI  - The GREek Atorvastatin and Coronary-heart-disease Evaluation (GREACE) study.

PMID- 12201623
TI  - Treatment with atorvastatin to the National Cholesterol Educational Program goal
      versus 'usual' care in secondary coronary heart disease prevention. The GREek
      Atorvastatin and Coronary-heart-disease Evaluation (GREACE) study.
AB  - BACKGROUND: Atorvastatin is very effective in reducing plasma low-density
      lipoprotein cholesterol (LDL-C) levels. However, there is no long-term survival
      study that evaluated this statin. PATIENTS-METHODS: To assess the effect of
      atorvastatin on morbidity and mortality (total and coronary) of patients with
      established coronary heart disease (CHD), 1600 consecutive patients were
      randomised either to atorvastatin or to 'usual' medical care. The dose of
      atorvastatin was titrated from 10 to 80 mg/day, in order to reach the National
      Cholesterol Education Program (NCEP) goal of LDL-C <100 mg/dl (2.6 mmol/l). All
      patients were followed up for a mean period of 3 years. MAIN OUTCOME MEASURES:
      Primary endpoints of the study were defined as death, non-fatal myocardial
      infarction, unstable angina, congestive heart failure, revascularisation
      (coronary morbidity) and stroke. Secondary endpoints were the safety and efficacy
      of the hypolipidaemic drugs as well as the cost-effectiveness of atorvastatin.
      RESULTS: The mean dosage of atorvastatin was 24 mg/day. This statin reduced total
      chlesterol by 36%, LDL-C by 46%, triglycerides by 31%, and non-high-density
      lipoprotein cholesterol (non-HDL-C) by 44%, while it increased HDL-C by 7%; all
      these changes were significant. The NCEP LDL-C and non-HDL-C treatment goals were
      reached by 95% (n = 759) and 97% (n = 776), respectively, of patients on
      atorvastatin. Only 14% of the 'usual' care patients received any hypolipidaemic
      drugs throughout the study and 3% of them reached the NCEP LDL-C treatment goal.
      The cost per quaility-adjusted life-year gained with atorvastatin was estimated
      at $US 8350. During this study 196 (24.5%) CHD patients on 'usual' care had a CHD
      recurrent event or died vs. 96 (12%) CHD patients on atorvastatin; risk ratio
      (RR) 0.49, confidence interval (CI) 0.27-0.73, p < 0.0001. In detail,
      atorvastatin reduced, in comparison to 'usual' care, total mortality (RR 0.57, CI
      0.39-0.78, p = 0.0021), coronary mortality (RR 0.53, CI 0.29-0.74, p = 0.0017),
      coronary morbidity (RR 0.46, CI 0.25-0.71, p < 0.0001), and stroke (RR 0.53, CI
      0.30-0.82, p = 0.034). All subgroups of patients (women, those with diabetes
      mellitus, arterial hypertension, age 60 to 75 years, congestive heart failure,
      recent unstable angina or prior revascularisation) benefited from treatment with
      atorvastatin. Withdrawal of patients because of side-effects from the
      atorvastatin group was low (0.75%) and similar to that of the 'usual' care group
      (0.4%). CONCLUSIONS: Long-term treatment of CHD patients with atorvastatin to
      achieve NCEP lipid targets significantly reduces total and coronary mortality,
      coronary morbidity and stroke, in comparison to patients receiving 'usual'
      medical care. Treatment with atorvastatin is well tolerated and cost-effective.

PMID- 12201624
TI  - Patient and physician satisfaction with rofecoxib in osteoarthritis: results of a
      post-marketing surveillance study in primary care in Germany.
AB  - A post-marketing surveillance study was conducted in Germany to assess the
      efficacy and tolerability of rofecoxib in the treatment of osteoarthritis (OA).
      Patients were eligible for inclusion in this study if they were being treated for
      the first time or being switched from other medications. More than three-quarters
      of the 80,371 patients enrolled in the study reported improved pain relief and
      function during treatment with rofecoxib (12.5 or 25 mg/day), including a
      reduction in pain experienced when walking on a flat surface or climbing or
      descending stairs. A majority of patients also considered that the duration of
      analgesia provided by rofecoxib was longer than with previous medications
      (predominantly non-steroidal anti-inflammatory drugs). Some 85% of patients
      reported an improvement in quality of life during rofecoxib therapy and a similar
      proportion considered once-daily rofecoxib to be a simpler regimen than their
      previous medications. Tolerability of rofecoxib was consistent with previous
      experience in controlled trials, with adverse events recorded in less than 1.5%
      of patients (n = 1090). No new or unexpected types of adverse events were
      recorded. A total of 81 serious adverse events were reported, corresponding to an
      event rate of approximately one per 1000 patient-years of treatment. Most of
      these serious events were not considered attributable to rofecoxib use.
      Physicians considered that rofecoxib provided better and more prolonged analgesia
      than previous medications and improved quality of life for more than 80% of
      patients, and regarded once-daily rofecoxib as a simpler treatment regimen than
      previous therapies in more than 90% of patients. Patient and physician
      satisfaction with rofecoxib was high in this survey. Most respondents regarded
      the drug as effective, easy to use, and a well-tolerated medication for the
      treatment of OA.

PMID- 12201625
TI  - The mRNA expression of cyclo-oxygenase-2 (COX-2) and vascular endothelial growth
      factor (VEGF) in human breast cancer.
AB  - AIMS: There is a growing body of evidence that cyclo-oxygenase 2 (COX-2) plays an
      important role in carcinogenesis and angiogenesis of human tumours. The present
      study aims to compare COX-2 expression in human breast cancer and adjacent non
      cancerous tissue (ANCT), and to identify any correlation between COX-2 and VEGF
      expression. METHODS: Total cellular RNA was extracted from frozen breast tissue
      samples according to standard methodology. The mRNA copy numbers for COX-2 and
      vascular endothelial growth factor 189 (VEGF-189) were determined 40 infiltrating
      carcinomas and 40 matched ANCT specimens using quantitative RT-PCR and TaqMan
      methodology. RESULTS: The COX-2 mRNA copy number per microg of RNA was two-fold
      higher in ANCT compared with the cancerous tissue (p = 0.01). Median mRNA copy
      number was 5.44 x 10(6) for ANCT and 2.30 x 10(6) for tumour, (ANCT range: 1 x
      10(6) to 4.12x 10(7)) (tumour range: 1.29 x 10(5) to 1.07 x 10(7)). There was a
      significant correlation between COX-2 and VEGF-189 mRNA copy numbers in the
      cancer specimens (correlation coefficient = 0.5528, p = 0.0076). CONCLUSIONS: COX
      2 mRNA is overexpressed in both human breast cancer and ANCT. We found higher
      levels in the matched ANCT which suggests that paracrine effects may be important
      in the role of COX-2 in mammary carcinogenesis. Furthermore, our results indicate
      that in human breast cancers COX-2 overexpression is linked to VEGF-189
      overexpression and therefore tumour angiogenesis.

PMID- 12201626
TI  - Acute myocardial infarction in a young South African Indian-based population:
      patient characteristics on admission and gender-specific risk factor prevalence.
AB  - BACKGROUND: Myocardial infarction (MI) is a complex disease caused by interaction
      of a number of genetic and environmental factors. This disease has reached
      epidemic proportions in South African Indian descendants. The aim of this study
      was to survey the prevalence of coronary heart disease risk factors in a sub
      group of young Indian patients (< or = 45 years) who presented to the Coronary
      Care Unit at the R. K. Khan Hospital in Durban, a major referral centre for
      patients with acute MI in the province of Natal. METHODS AND RESULTS: A total of
      245 patients < or = 45 years of age were recruited from patients consecutively
      admitted to the Coronary Care Unit at the R. K. Khan Hospital, Durban, KwaZulu
      Natal, South Africa between 1996 and 1999 with a diagnosis of acute MI. All
      patients were of Indian origin living in the Durban area in the province of
      KwaZulu-Natal. Demographic and risk factor data were obtained from all patients
      and included anthropometric measures, family history and the traditional
      cardiovascular risk factor assessment (smoking, lipids, hypertension, and
      diabetes mellitus). Clinical data included in-hospital presentation, management
      and complications and angiographic classification of coronary atherosclerosis.
      The most prevalent risk factors were previous: smoking (74%), and
      hypertriglyceridaemia (54%). Only 14% of the population presenting with an acute
      MI were women. Smoking was more common among men (81%) than in women (35%).
      Abnormal high density lipoprotein (HDL) cholesterol levels were detected in 38%
      of the patients with a dear gender difference: 43% and 9%, in men and women,
      respectively. In contrast hypertension was more prevalent in young women with MI
      than in men: 38% and 19%, respectively. Coronary angiography was performed in 79
      patients on admission; a single vessel stenosis was found in 28%, two vessel
      disease in 20% and triple vessel disease in 52%, respectively. On admission, 92%
      of patients were in Killip class I. Overt heart failure and cardiogenic shock
      were uncommon and were seen in 3.3% and 0.8%, respectively. Patients who received
      thrombolytic therapy had fewer complications (8%) compared to those who did not
      (11%). However, the difference towards a benefit of thrombolysis did not reach
      significance. Recurrent angina (6%) was the commonest complication, while
      ventricular arrhythmias were observed in 2% of patients. There was a strong
      familial link: 54% of the patients had a family background of coronary heart
      disease (CHD) while 42% and 41% had family members who suffered from diabetes
      mellitus and hypertension, respectively. CONCLUSION: Smoking and dyslipidaemia
      (predominantly hypertriglyceridaemia, and low HDL-cholesterol) were the most
      common cardiovascular risk factors of MI in young South African Indians. A strong
      familial link was observed not only for a history of CHD/MI, but also for
      hypertension and diabetes mellitus, supporting a genetic basis for the
      development of premature CHD. Therefore, further analysis of potential genetic
      factors such as variance of genes involved in vascular homeostasis, haemostatic
      factors, lipid metabolism and other metabolic factors seems warranted.

PMID- 12201627
TI  - Object and spatial relational memory in adult rhesus monkeys is impaired by
      neonatal lesions of the hippocampal formation but not the amygdaloid complex.
AB  - Adult rhesus monkeys with neonatal aspiration lesions of the hippocampal
      formation or the amygdaloid complex (including their respective subjacent
      cortices) and their age-matched controls were tested on the transverse patterning
      problem (A+ vs. B-, B+ vs. C- and C+ vs. A-) and a spatial version of the delayed
      nonmatching-to-sample (DNMS) task with delays of 10 s to 30 s, 60 s, 120 s, and
      600 s. Monkeys with neonatal damage to the amygdaloid complex learned both tasks
      and did not differ from controls at any delay of the spatial DNMS task. Monkeys
      with neonatal hippocampal damage, however, were unable to learn transverse
      patterning, though they easily transferred to a linear series (A+ vs. B-, B+ vs.
      C-, and C+ vs. X-). Three of the four were also unable to reach criterion on the
      spatial DNMS task within the limits of testing, and the performance of all four
      monkeys deteriorated with increasing choice delays. The data suggest a role of
      the primate hippocampal region in both object and spatial relational learning.

PMID- 12201628
TI  - Tetanic stimulation of schaffer collaterals induces rhythmic bursts via NMDA
      receptor activation in rat CA1 pyramidal neurons.
AB  - Exploring the principles that regulate rhythmic membrane potential (Vm)
      oscillations and bursts in hippocampal CA1 pyramidal neurons is essential to
      understanding the theta rhythm (theta). Recordings were performed in vitro in
      hippocampal slices from young rats, and a group of the recorded CA1 pyramidal
      cells were dye-filled with carboxifluorescein and immunolabeled for the R1
      subunit of the NMDA receptor. Tetanic stimulation of Schaffer collaterals (SCs)
      and iontophoresis of glutamate evoked rhythmic Vm oscillations and bursts
      (approximately 10 mV, approximately 7 Hz, 2-5 spikes per burst) in cells (31%)
      placed close to the midline ("medial cells"). Rhythmic bursts remained under
      picrotoxin (10 microM) and Vm oscillations persisted with tetrodotoxin (1.5
      microM), but bursts were blocked by AP5 (25 microM) and Mg2+-free solutions.
      Depolarization and AMPA never induced rhythmic bursts. The rest of the neurons
      (69%), recorded closer to the CA3 region ("lateral cells"), discharged
      rhythmically single repetitive spikes under SC stimulation and glutamate in
      control conditions, but fired rhythmic bursts under similar stimulation, both
      when NMDA was applied and when non-NMDA receptors were blocked with CNQX (20
      microM). Medial cells exhibited a larger NMDA current component and a higher
      NMDAR1 density at the apical dendritic shafts than lateral cells, suggesting that
      these differences underlie the dissimilar responses of both cell groups. We
      conclude that the "theta-like" rhythmic oscillations and bursts induced by
      glutamate and SC stimulation relied on the activation of NMDA receptors at the
      apical dendrites of medial cells. These results suggest a role of CA3 pyramidal
      neurons in the generation of CA1 theta via the activation of NMDA receptors of
      CA1 pyramidal neurons.

PMID- 12201629
TI  - Enhancement of temporal and spatial synchronization of entorhinal gamma activity
      by phase reset.
AB  - The synchronization of cortical gamma oscillatory activity (25-80 Hz) is thought
      to coordinate neuronal assemblies in the processing and storage of information.
      The mechanism by which independently oscillating and distantly located cortical
      zones become synchronized is presumed to involve activity in corticocortical
      connections, although evidence supporting this conjecture has only been indirect.
      In the present study, we show that activation of synaptic inputs within and to
      the medial entorhinal cortex (mEC) of the in vitro isolated guinea pig brain
      preparation resets the phase of ongoing gamma activity induced by muscarinic
      receptor agonism with carbachol (frequency: 24 +/- 2 Hz at 32 degrees C). Phase
      reset was associated with a transient enhancement of the synchronization of gamma
      activity recorded at distant (>1 mm) mEC sites, across which low coherence
      (>0.75) was observed before stimulation. This increase in synchronization, as
      measured by cross-correlation analysis, was restricted to a maximal period of 200
      ms after either local mEC or CA1 afferent stimulation. The results provide direct
      evidence that synaptic activation can enhance the rhythmic synchronization of
      spatially remote, independently oscillating neuronal assemblies in the mEC
      through a mechanism of synaptically evoked phase reset. Dynamic functional
      grouping of oscillatory discharges across long distances in the mEC may underlie
      coding processes involved in the integration and storage of incoming information
      and thus may be important for the role of this region in memory processes.

PMID- 12201631
TI  - Development of spatial firing in the hippocampus of young rats.
AB  - The hippocampal formation participates in learning and memory, particularly that
      of a spatial nature. In adult rats, individual CA1 pyramidal neurons only fire
      when the animal visits specific locations in an environment, the "place field" of
      the neuron. Other structures (postsubiculum, thalamus, cingulum) contain neurons
      that code for the animal's instantaneous head direction. Previous work has shown
      that the rat hippocampal formation undergoes anatomical and neurophysiological
      maturation during the first 2 months of life and that rats <40 days of age are
      impaired in spatial navigation tasks. Here we show that the locational firing of
      CA1 pyramidal neurons is both less specific and less stable in animals aged <50
      days. However, preliminary results indicate that head directional firing recorded
      around day 30 is essentially identical to that seen in adult animals. Therefore,
      the development of reliable, spatially specific place cell activity parallels the
      developmental time course of spatial navigational ability, but head directional
      firing appears before full maturation of the hippocampus.

PMID- 12201630
TI  - Changes in protein kinase C (PKC) activity, isozyme translocation, and GAP-43
      phosphorylation in the rat hippocampal formation after a single-trial contextual
      fear conditioning paradigm.
AB  - The hippocampus plays an important role in spatial learning and memory. However,
      the biochemical alterations that subserve this function remain to be fully
      elucidated. In this study, rats were subjected to a single-trial contextual fear
      conditioning (CFC) paradigm; the activation of different protein kinase C (PKC)
      subtypes and the levels and phosphorylation of the plasticity-associated protein
      GAP-43 were assayed in the hippocampus at varying times after training. We
      observed a rapid activation of hippocampal PKC (15 min through 24 h), with
      differential translocation of the PKC isotypes studied. At early times after CFC
      (15-90 min), PKCalpha and PKCgamma translocated to the membrane, while PKCbetaII
      and PKCepsilon moved more transiently (15 to 30 min) to the cytosol. These PKC
      isotypes returned to the membrane at later time points after CFC. Correlating
      with these changes in PKC translocation and activity, there was an early decrease
      in GAP-43 phosphorylation followed by a more sustained increase from 1.5-72 h.
      GAP-43 protein levels were also increased after 3 h, and these levels remained
      elevated for at least 72 h. These changes in PKC and GAP-43 were specific to the
      CFC trained animals and no changes were seen in animals exposed to the same
      stimuli in a non-associative fashion. Comparison of translocation of different
      PKC isotypes with the changes in GAP-43 phosphorylation suggested that PKCbetaII
      and PKCepsilon may mediate both the early changes in the phosphorylation of this
      protein and the increases in GAP-43 expression at later times after CFC.

PMID- 12201632
TI  - Peak firing rates of rat anterodorsal thalamic head direction cells are higher
      during faster passive rotations.
AB  - Head direction cells discharge selectively when the head of the animal is
      oriented in a specific direction. The goal of this study was to determine how
      sensory signals arising from passive rotations (e.g., triggered by vestibular
      stimulation and dynamic visual inputs) influence the responses of anterodorsal
      thalamic head direction cells in the absence of voluntary movement cues (e.g.,
      motor command, efference copy, and associated kinesthetic signals). Three
      unrestrained rats consumed water from a reservoir at the center of a circular
      platform while passively subjected to sinusoidal rotatory oscillations at fast
      (153 +/- 27 degrees/s, sd) and slow (38 +/- 15 degrees/s) peak velocities. In 14
      anterodorsal thalamic head direction cells, the preferred directions, angular
      response ranges and baseline firing rates remained stable, but the peak firing
      rates were, on average, 36% higher during the fast rotations (Wilcoxon matched
      pairs test, p < 0.001; variation range: +11% to approximately +100%). No cell
      changed its peak firing rate by less than 10%, while three cells (21%) increased
      their peak firing rates by more than 50%. The velocity-dependent increase in peak
      firing rates was similar for left and right rotations, and the skewness of the
      directional response curves were not significantly different between left and
      right turns (Wilcoxon matched-pairs tests, n = 14, ns). These results show that
      sensory signals concerning self-movements modulate the responses of the head
      direction cells in the absence of active locomotion.

PMID- 12201633
TI  - Role of medial temporal lobe in extensive retrieval of task-related knowledge.
AB  - The role of medial temporal lobe (MTL) in deep semantic processing was examined
      in a triple semantic judgment task in which subjects were asked to decide which
      one of the two bottom words was more semantically fit to the top word. By
      changing the number of bottom words that are semantically related to the top
      word, we can disassociate effects of reactivating the "old" semantic associations
      and effects of establishing "new" semantic associations on the MTL. The results
      of event-related fMRI analysis indicated that MTL was more activated in the
      retrieval of old semantic associations than in the establishment of new semantic
      associations. The function of MTL in this semantic judgment task was explained as
      subserving the process of extensive retrieval of task-related knowledge.

PMID- 12201634
TI  - Post-training excitotoxic lesions of the dorsal hippocampus attenuate forward
      trace, backward trace, and delay fear conditioning in a temporally specific
      manner.
AB  - The present study sought to determine whether post-training excitotoxic lesions
      of the dorsal hippocampus would disrupt retention of fear conditioned using a
      trace procedure. Rats were trained using one of six procedures. Forward trace
      conditioning consisted of 10 trials in which a 16-s tone conditional stimulus
      (CS) was followed by a 28-s stimulus-free trace interval and then a mild
      footshock unconditional stimulus (US). We used two forms of delay conditioning
      where the tone and footshock co-terminated. Short delay used a 16-s tone and long
      delay used a 46-s tone. Backward trace conditioning was the same as forward
      trace, except that the order of the CS and US was reversed. CS-only and US-only
      were similar to forward trace except that the footshock or tone, respectively,
      was eliminated. One day later, animals received either an N-methyl-D-aspartate
      (NMDA)-induced lesion of the dorsal hippocampus or sham surgery. One week later,
      the rats were tested for freezing to the tone in a novel context. The next day,
      they were tested for freezing to the original training context. Hippocampal
      lesioned trace conditioned rats showed significantly less freezing during the
      tone compared with their sham lesioned controls. The lesion did not affect
      freezing during the tone in delay conditioning, nor in the other training
      conditions. During the 1-min period after tone offset, there was a trend in all
      hippocampal lesioned animals toward a deficit in freezing, compared with their
      corresponding sham lesioned controls, although only short delay, forward and
      backward trace groups showed a significant deficit. Hippocampal lesions also
      attenuated contextual conditioning. Thus, the hippocampus is critical for the
      consolidation and/or expression of a trace fear conditioned stimulus.

PMID- 12201635
TI  - Telemetry system for reliable recording of action potentials from freely moving
      rats.
AB  - Recording single cells from alert rats currently requires a cable to connect
      brain electrodes to the acquisition system. If no cable were necessary, a variety
      of interesting experiments would become possible, and the design of other
      experiments would be simplified. To eliminate the need for a cable we have
      developed a one-channel radiotelemetry system that is easily carried by a rat.
      This system transmits a signal that is reliable, highly accurate and can be
      detected over distances of > or = 20 m. The mobile part of the system has three
      components: (1) a headstage with built-in amplifiers that plugs into the
      connector for the electrode array on the rat's head; the headstage also
      incorporates a light-emitting diode (LED) used to track the rat's position; (2) a
      backpack that contains the transmitter and batteries (2 N cells); the backpack
      also provides additional amplification of the single cell signals; and (3) a
      short cable that connects the headstage to the backpack; the cable supplies power
      to the headstage amplifiers and the LED, and carries the physiological signals
      from the headstage to the backpack. By using a differential amplifier and
      recording between two brain microelectrodes the system can transmit action
      potential activity from two nearly independent sources. In a future improvement,
      two transmitters with different frequencies would be used telemeter signals from
      four microelectrodes simultaneously.

PMID- 12201636
TI  - Human declarative memory formation: segregating rhinal and hippocampal
      contributions.
AB  - The medial temporal lobe (MTL) is the core structure of the declarative memory
      system, but which specific operation is performed by anatomically defined MTL
      substructures? One hypothesis proposes that the hippocampus carries out an
      exclusively mnemonic operation during declarative memory formation that is
      insensitive to content, whereas the rhinal cortex carries out an operation
      supporting memory formation indirectly. To explore the interaction between a
      salient item feature and memory formation, we contrasted neural correlates of
      memory formation of high- and low-frequency words. Event-related potentials
      (ERPs) were recorded via depth electrodes from within the MTL in nine epilepsy
      patients while they memorized single words. To assess memory formation, ERPs to
      words subsequently recalled in a free recall test were contrasted with ERPs to
      forgotten words. More high- than low-frequency words were remembered. High
      frequency words led to distinct ERP subsequent memory effects in rhinal cortex
      and hippocampus. Low-frequency words, however, were only associated with the
      hippocampal ERP effect. The anatomically restricted interaction between word
      frequency and memory formation might indicate a semantically affected operation
      in the parahippocampal region supporting memory formation indirectly. By
      contrast, the missing interaction in hippocampal recordings might suggest a
      direct correlate of declarative memory formation that is insensitive to item
      properties.

PMID- 12201637
TI  - Semantic knowledge in patient H.M. and other patients with bilateral medial and
      lateral temporal lobe lesions.
AB  - We investigated the effects of damage to the medial temporal lobe (MTL) and
      anterolateral temporal cortex on semantic knowledge. We studied eight male
      controls, two patients with lesions limited to the hippocampal formation, three
      postencephalitic patients with extensive MTL lesions and variable damage to the
      lateral temporal cortex, and patient H.M. (whose lesion is limited mostly to the
      MTL, but who also has minimal damage to the anterolateral cortex). On 13 tests of
      semantic memory, patients with lesions limited to the hippocampal formation
      performed similarly to controls. Postencephalitic patients were mildly to
      moderately impaired on most tests. Patient H.M.'s performance was impaired on
      only a few tests and was less severely impaired overall than the three
      postencephalitic patients. A ranking of test scores showed a direct relationship
      between impairment and the extent of damage to lateral temporal cortex. These
      findings, and related findings from other studies, point to the importance of
      anterolateral temporal cortex for semantic knowledge. Patient H.M. performed
      uniquely in certain respects. For example, when providing definitions of objects,
      he made many grammatical errors. In contrast, the other patients with large MTL
      lesions made no more errors than those made by controls. Considering that H.M.'s
      lesion, both medially and laterally, is less extensive than the lesions in these
      other patients, it appears unlikely that his shortcomings in language production
      are related to his temporal lobe lesion.

PMID- 12201638
TI  - Entorhinal axons exhibit sprouting in CA1 subfield of the adult hippocampus in a
      rat model of temporal lobe epilepsy.
AB  - Intracerebroventricular kainic acid administration in rat, a model of temporal
      lobe epilepsy, results in CA3 pyramidal neuron degeneration leading to
      deafferentation of CA1 pyramidal neurons. Denervation in CA1 shows a near
      complete recovery of synaptic density over 2-3 months, but the source of axons
      participating in the reinnervation is not clear. This study investigated the
      contribution of the entorhinal cortex in this reinnervation by comparing the
      distribution of the entorhinal axons in the CA1 subfield between the intact
      hippocampus and the CA3-lesioned hippocampus at 3 months after administration of
      kainic acid. Entorhinal axons were visualized by anterograde tracing using
      injections of the biotinylated dextran amine into the entorhinal cortex. In the
      CA1 subfield of the intact hippocampus, entorhinal axons were conspicuous in the
      alveus and the stratum lacunosum moleculare. The distribution in the strata
      oriens, pyramidale, and radiatum was sparse and was characterized by isolated
      entorhinal fibers of the alvear pathway crossing these strata to the stratum
      lacunosum moleculare. However, after kainic acid-induced CA3 lesion, the density
      of entorhinal axons increased significantly in the CA1 stratum radiatum (375% of
      the intact hippocampus), as a large number of axons emanating from the entorhinal
      fiber plexus in the stratum lacunosum moleculare invaded the stratum radiatum.
      The stratum radiatum also exhibited wavy entorhinal axons filled with boutons and
      oriented parallel to the stratum pyramidale, suggesting collateral sprouting from
      entorhinal axons traversing the stratum radiatum. Thus, a significant aberrant
      sprouting of entorhinal axons occurs into the CA1 stratum radiatum after CA3
      lesion. The sprouted fibers appear to come from both entorhinal fiber plexus in
      the stratum lacunosum moleculare (translaminar sprouting) and entorhinal axons
      traversing the stratum radiatum (intralaminar sprouting). However, the major
      contribution appears to be from the entorhinal plexus in the stratum lacunosum
      moleculare. This aberrant sprouting may lead to altered afferent excitatory
      connectivity in the CA1 subfield and contribute to the persistent CA1
      hyperexcitability that occurs after the CA3 lesion.

PMID- 12201639
TI  - Effects of lesions to the hippocampus or the fornix on allocentric conditional
      associative learning in rats.
AB  - Rats with lesions of the fornix, the hippocampus, or normal control animals were
      trained on a visual-spatial conditional associative learning task in which they
      had to learn to go to a particular location based on the presence of a specific
      visual cue; the rats approached the cues from different directions. Animals with
      damage of the fornix were able to learn the task at a rate comparable to that of
      the control animals. The performance of the hippocampal rats was significantly
      impaired as compared with the control group. Both the fornix and the hippocampal
      animals were significantly impaired on a spatial working memory task, the eight
      arm radial maze. These findings suggest that, under certain conditions, a
      functional dissociation exists between the effects of damage to the fornix or the
      hippocampus and that the fornix may be only selectively involved in spatial
      learning and memory.

PMID- 12201640
TI  - BDNF-triggered events in the rat hippocampus are required for both short- and
      long-term memory formation.
AB  - Information storage in the brain is a temporally graded process involving
      different memory types or phases. It has been assumed for over a century that one
      or more short-term memory (STM) processes are involved in processing new
      information while long-term memory (LTM) is being formed. Because brain-derived
      neutrophic factor (BDNF) modulates both short-term synaptic function and activity
      dependent synaptic plasticity in the adult hippocampus, we examined the role of
      BDNF in STM and LTM formation of a hippocampal-dependent one-trial fear-motivated
      learning task in rats. Using a competitive RT-PCR quantitation method, we found
      that inhibitory avoidance training is associated with a rapid and transient
      increase in BDNF mRNA expression in the hippocampus. Bilateral infusions of
      function-blocking anti-BDNF antibody into the CA, region of the dorsal
      hippocampus decreased extracellular signal-regulated kinase 2 (ERK2) activation
      and impaired STM retention scores. Inhibition of ERK1/2 activation by PD098059
      produced similar effects. In contrast, intrahippocampal administration of
      recombinant human BDNF increased ERK1/2 activation and facilitated STM. The
      infusion of anti-BDNF antibody impaired LTM when given 15 min before or 1 and 4
      hr after training, but not at 0 or 6 hr posttraining, indicating that two
      hippocampal BDNF-sensitive time windows are critical for LTM formation. At the
      same time points, PD098059 produced no LTM deficits. Thus, our results indicate
      that endogenous BDNF is required for both STM and LTM formation of an inhibitory
      avoidance learning. Additionally, they suggest that this requirement involves
      ERK1/2-dependent and -independent mechanisms.

PMID- 12201641
TI  - The hippocampus and Pavlovian fear conditioning: reply to Bast et al.

PMID- 12201642
TI  - A 72-year-old man with prostate cancer.

PMID- 12201644
TI  - Docetaxel/platinum combination provides quality-of-life advantage over
      vinorelbine/cisplatin in advanced lung cancer.

PMID- 12201643
TI  - Prostate-specific antigen as a marker of disease activity in prostate cancer.
AB  - Despite the impact of prostate-specific antigen (PSA) testing on the detection
      and management of prostate cancer, controversy about its usefulness as a marker
      of disease activity continues. This review, based on a recent roundtable
      discussion, examines whether PSA measurements can be used rationally in several
      clinical settings. Following radical prostatectomy and radiation therapy,
      prediction of survival by PSA level is most reliable in high-risk patients. PSA
      doubling time after radiation therapy is the strongest predictor of biochemical
      failure. PSA measurements have been associated with inconsistent results
      following hormonal treatment; reduced PSA levels may result from antiandrogen
      treatment, which decreases expression of the PSA gene, and therefore, the level
      of PSA production. In the setting of primary and secondary cancer prevention, PSA
      is important in risk stratification when selecting patients for studies. Part 1
      of this two-part article, which concludes in the September issue, focuses on the
      physiology of PSA, its measurement and use in clinical practice, and its
      predictive value following radical prostatectomy and radiation therapy.

PMID- 12201645
TI  - What is the optimal therapy for childhood AML?
AB  - The use of intensive therapy overa brief period of time has produced dramatic
      improvements in outcome for pediatric patients with acute myelogenous leukemia
      (AML), as has been demonstrated in studies by the major cooperative groups in the
      United States and Europe. Still, despite high-intensity chemotherapy and bone
      marrow transplantation, only about half of the children diagnosed with AML are
      cured. Future improvements are unlikely to come from further increases in
      chemotherapy intensity. Alternative approaches, such as risk-directed therapy
      based on different prognostic criteria; differentiation therapy with all-trans
      retinoic acid (ATRA, Vesanoid), arsenic trioxide (Trisenox), or azacytidine; and
      immunotherapy with monoclonal antibodies, tumor vaccines, or cytokines may lead
      to further advances.

PMID- 12201646
TI  - Clinical trials referral resource. Current clinical trials of the Cancer Trials
      Support Unit (CTSU), an NCI pilot program.

PMID- 12201647
TI  - Mathematical modeling for breast cancer risk assessment. State of the art and
      role in medicine.
AB  - Women at increased risk of breast cancer have important opportunities for early
      detection and prevention. There are, however, serious drawbacks to the available
      interventions. The magnitude of breast cancer risk is a crucial factor in the
      optimization of medical benefit when considering the efficacy of risk-reduction
      methods, the adverse effects of intervention, and economic and quality-of-life
      outcomes. Breast cancer risk assessment has become increasingly quantitative and
      is amenable to computerization. The assembly of risk factor information into
      practical, quantitative models for clinical and scientific use is relatively
      advanced for breast cancer, and represents a paradigm for broader risk management
      in medicine. Using a case-based approach, we will summarize the major breast
      cancer risk assessment models, compare and contrast their utility, and illustrate
      the role of genetic testing in risk management. Important considerations relevant
      to clinical oncology practice include the role of risk assessment in cancer
      prevention, the logistics of implementing risk assessment, the ramifications of
      conveying risk information with limited genetic counseling, and the mechanisms
      for genetics referral. Medical professionals can embrace new preventive medicine
      techniques more effectively by utilizing quantitative methods to assess their
      patients' risks.

PMID- 12201648
TI  - Current management of depression in cancer patients.
AB  - Depression is a common but treatable condition among cancer patients. Screening
      for depression can be done simply and effectively, and a variety of practical
      treatment strategies are available. Numerous factors should be considered when
      prescribing medications from an ever-growing antidepressant armamentarium,
      including selective serotonin-reuptake inhibitors, serotonin norepinephrine
      reuptake inhibitors, serotonin antagonist-reuptake inhibitors, norepinephrine
      dopamine modulators, monoamine oxidase inhibitors, reversible inhibitors of
      monoamine oxidase type A, tricyclic antidepressants, and psychostimulants. Other
      treatment options include electroconvulsive therapy and numerous forms of
      psychotherapy. The judicious use of medication and supportive therapies should
      significantly alleviate depression and enable the patient to navigate the cancer
      course with dignity, purpose, and the best quality of life possible.

PMID- 12201649
TI  - Immunisation of Indian major carps against Aeromonas hydrophila by
      intraperitoneal injection.
AB  - The Indian major carps Catla catla, Labeo rohita and Cirrhinus mrigala were
      immunised against the potent bacterial fish pathogen, Aeromonas hydrophila by the
      intraperitoneal route, in field conditions. Two different polyvalent antigen
      preparations namely, whole cell and extracellular products (ECP) were used.
      Immunisation schedule consisting of a single booster dose given 28 days after
      priming resulted in a good agglutinating antibody response in the carps. Kinetics
      of the response were similar in the three carp species with both whole cell and
      ECP. Upon challenge with virulent strains, relative percent survival as high as
      80-90% was recorded. Indian major carps are the most important freshwater species
      cultured in India and it is essential that they are protected against infections
      of A. hydrophila, a scourge of freshwater fish worldwide.

PMID- 12201650
TI  - In vitro toxicity and interactions of environmental contaminants (Arochlor 1254
      and mercury) and immunomodulatory agents (lipopolysaccharide and cortisol) on
      thymocytes from lake trout (Salvelinus namaycush).
AB  - The immunotoxicity of chemical combinations commonly encountered by the lake
      trout (Salvelinus namaycush) immune system was the focus of this study. It was
      hypothesised that combinations of an environmental contaminant (mercuric chloride
      or Aroclor 1254) and an immunomodulatory agent (bacterial endotoxin or cortisol)
      might interact to produce a greater toxicity than that of the environmental
      contaminant alone at concentrations typically encountered in piscine blood and
      other tissues. Thus lake trout thymocytes were isolated and treated with mercuric
      chloride or Aroclor 1254 in the presence and absence of cortisol or
      lipopolysaccharide. Incubations were performed for 6 or 20 h at 4 degrees C or 10
      degrees C. Lipopolysaccharide did not affect the toxicity of either contaminant.
      In contrast, cortisol enhanced the toxicity of both environmental contaminants.
      Hence, stressors that lead to increased cortisol production, but not
      lipopolysaccharide directly, may increase the toxicity of mercury and Aroclor
      1254 to lake trout thymocytes.

PMID- 12201651
TI  - Different bacterial lipopolysaccharides as toxicants and stressors in the shrimp
      Palaemon elegans.
AB  - This study compares the in vivo haemocytic response of shrimp, Palaemon elegans
      (Rathke) to different types of LPS injection. In particular it investigates to
      what degree and speed the haemocytopenia varies between LPSs from different
      sources. It further compares the tolerated doses of different LPSs in these
      animals and finds substantial differences in the various toxicity types. The work
      then relates this to blood glucose levels and stress-linked variations in
      glycaemic status. The order of LPS decreasing toxicity determined by LD50 at 96 h
      was: Salmonella enteritidis, Serratia marcescens, Pseudomonas aeruginosa 10,
      Escherichia coli K-235 and E. coli 0111:B4. Eyestalkless animals were more
      sensitive to LPS. The effects of injected LPS on circulating total blood cell
      count (THC) was tested. The results show that LPS caused a decrease in THC 8 h
      after injection and then the THC returned to the initial level and this effect
      depended on the LPS tested. E. coli K-235 was the most effective in causing
      haemocytopenia followed by E. coli 0111:B4, S. enteritidis, S. marcescens, and P.
      aeruginosa 10. Moreover, LPS-induced increases in the blood glucose level and the
      time and dose related curves of response obtained depended on the type of LPS
      tested. E. coli K-235 LPS was again the most effective in elevating blood glucose
      followed by E. coli 0111:B4, S. marcescens, S. enteritidis and then P. aeruginosa
      10. No significant hyperglycaemia was induced in eyestalkless animals. An inverse
      order relationship between toxicity (LD50) and stress responses (hyperglycaemia
      and THC decrease) may suggest a defensive and adaptive role of the latter in
      occasional septicaemia.

PMID- 12201653
TI  - Gene expression in haemocytes of kuruma prawn, Penaeus japonicus, in response to
      infection with WSSV by EST approach.
AB  - Gene expression in haemocytes of the kuruma prawn (Penaeus japonicus) was
      investigated using an expressed sequence tag (EST) approach. Partial nucleotide
      sequences of cDNA library clones constructed from normal and white spot syndrome
      virus (WSSV)--infected P. japonicus haemocytes were determined. Of 635 clones
      obtained from the normal library, 284 (44.7%) significantly matched sequences in
      GenBank, and of 370 clones obtained from WSSV-infected library, 174 (47.0%)
      significantly matched sequences in the database. One hundred fifty-two deduced
      proteins were newly identified. Of these, 28 types were involved in biodefence.
      For the prophenoloxidase system, there are prophenoloxidase, coagulation factor G
      beta chain precursor, factor D, Masquarade-like protease, transglutaminase
      (TGase), clottable protein and eight types of protease inhibitors (two types of
      antileukoproteinase, alpha-2-macroglobulin, chelonianin, elastase inhibitor, two
      types of Kazal inhibitor and Kunitz-type inhibitor). For antibacterial peptides,
      there are bactinecin 11, penaeidin-2 precursor and lysozyme c type. The others
      defence-related proteins are basophil leukocyte interleukin-3-regulated protein,
      natural killer enhancing factor (NK-EF), integral membrane protein (CD34+), ESM
      1, Notch homologue and Drac homologue. For the adhesion proteins, there are beta
      integrin, cell adhesion molecule (CAM) and three types of collagens. All ESTs
      representing protease inhibitors and tumour-related proteins were found only in
      the WSSV-infected library. Those encoding for apoptotic peptides were expressed
      at high levels in infected library. The putative defence proteins accounted for
      2.7% of total ESTs in a normal shrimp library and 15.7% of the total ESTs in an
      infected library.

PMID- 12201652
TI  - Mechanisms of nonspecific cytotoxic cell regulation of apoptosis: cytokine-like
      activity of Fas ligand.
AB  - The role of FasL/FasR pathways of immunoregulation of programmed cell death in
      teleost cytotoxic innate immunity has not been previously examined. In the
      present study, constitutive cytosolic soluble FasL (sFasL) was detected in
      anterior kidney (AK), peripheral blood (PBL) and liver NCC obtained from tilapia.
      Ligation of NCC by tumour cells caused the release of sFasL that was associated
      with lysis of HL-60 targets in 14 h killing assays. Evidence that sFasL mediated
      this activity was that anti-(human) FasL inhibited tilapia and catfish (cf.) NCC
      lysis of FasR+ HL-60 tumour cells. Inhibition was concentration dependent. Lysis
      of IM-9 targets (12% positive for FasR) by (cf.) anterior kidney and PBL NCC was
      only partially inhibited by anti-FasL mab. Activated NCC from both species were
      negative for the expression of membrane FasL and FasR. These data confirmed that
      NCC lyse sensitive tumour cells by multiple effector pathways. Pretreatment of
      (FasR+) HL-60 cells with anti-FasR mab completely inhibited cf. cytotoxicity at
      low (100:1) E:T ratios. Anti-FasR mab did not inhibit the lysis of IM-9 targets
      by cf. NCC. This study demonstrated that for catfish and tilapia, initial target
      cell conjugate formation was required; however, the terminal killing mechanism
      depended on at least two different pathways of cytotoxicity. One pathway depended
      on the release of preformed soluble FasL by activated NCC in the presence of FasR
      positive target cells. A second pathway has yet to be determined.

PMID- 12201654
TI  - The mental health needs of children and adolescents.

PMID- 12201655
TI  - A program to educate school nurses about mental health interventions.
AB  - Concerned with the increasing incidence of mental health problems in children and
      adolescents and the impact of these problems on students' school success and
      predisposition to self- and other-directed violence, the Multnomah Education
      Service District Department of School Health Services determined to become
      proactive by providing preventive interventions for students experiencing actual
      or potential mental health problems. An educational program was designed to
      assist school nurses in the identification of potential mental health problems.
      In addition, information about appropriate interventions for students at risk for
      aggression, violence, and other mental health pathology was presented. The
      program involved education on mental health assessment and intervention, as well
      as expert psychiatric clinical support for the development of student support
      groups. School nurses were then challenged to develop practice improvement
      projects incorporating this knowledge for a group of students in their work
      setting. This introductory article describes the project's general rationale and
      implementation process. The four articles following in this issue of The Journal
      of School Nursing describe the goals, implementation, and outcomes of the
      practice improvement projects developed for early intervention with students
      exhibiting attention disorders, school absenteeism, social withdrawal, and
      depression.

PMID- 12201656
TI  - Small group intervention for children with attention disorders.
AB  - Children with attention disorders can experience adverse long-term effects on
      academic performance, vocational success, and socioemotional development. They
      experience some level of functional impairment that extends across settings,
      including the home and school. In combination with medication, group
      interventions with school-age children were found to be effective for enhancing
      social behavior. This article describes two practice improvement projects that
      provided group experiences for children with attention-deficit/hyperactivity
      disorder (ADHD) symptoms, including disruptive behavior. Four skill domains were
      addressed: communication, friendship, self-control, and social problem solving.
      One project provided activities for early school-age children with ADHD who were
      treated with medication only. Another provided a support group on self-management
      for freshman boys with ADHD who were also treated with medication only. In both
      projects, the disruptive behavior of the participants decreased by the end of the
      group sessions.

PMID- 12201657
TI  - A support group for absentee middle school students.
AB  - For this practice improvement project, an interview guide was developed to
      identify chronically absent middle school students' reasons for school absence.
      Of the 17 students interviewed, 82% (n = 14) identified illness as the reason for
      absence, although they rarely saw a health care provider. The students all shared
      dreams for the future; 50% involved further education, and 50% involved job
      training. A support group intervention was offered to the 17 students during
      spring term. Only three students were able to participate in a weekly group
      meeting for 5 weeks. Two of the three students were depressed and referred to
      their health care providers for evaluation. The topics presented to the group
      included being sick and options available, setting weekly attendance goals,
      identifying depressive symptoms and what they mean, and likes and dislikes about
      school. The support group occurred late in the school year, so its effect on
      attendance was not determined.

PMID- 12201658
TI  - Small group experience for socially withdrawn girls.
AB  - Social competence is the effectiveness of social interaction behavior. Given its
      link to mental health outcomes, it is an important consideration in child and
      adolescent development. Social withdrawal is associated with depression. Socially
      withdrawn children make few social initiations and tend to be isolated in their
      play, further limiting their social involvement. To develop effective social
      behavior, experiences must be provided to learn relationship skills. This
      practice improvement project provided a small group experience for five socially
      withdrawn school-age girls. Weekly group meetings provided a social situation in
      which conversations could occur around a shared snack and craft project. The
      school nurse facilitated self-assertion and the expression of prosocial behavior
      in a socially safe (nonrejecting) environment and promoted social problem
      solving. On completion of the program, the participants not only showed more
      effective social reasoning and social skills, but developed friendships with each
      other that lasted beyond the life of the group.

PMID- 12201659
TI  - A support group intervention for at-risk female high school students.
AB  - School nurses have an opportunity to engage in early intervention with high-risk
      adolescents. School-based support groups for depressed adolescents have been
      effective when aimed at providing skills training as well as emotional support.
      In this practice improvement project, 14 high-risk female adolescents from two
      high schools were identified on the basis of signs associated with depression.
      The students completed a questionnaire about risk and protective factors during
      the assessment and at the end of the intervention. Twelve students participated
      in a weekly support group designed to enhance coping skills and to provide
      emotional support. Assessment revealed that the students were at suicide risk. At
      the conclusion of the group intervention, there was a 55% decrease in suicidal
      ideation, a 27% decrease in perceived stress, and a 26% decrease in family
      distress. In addition, most of the students became engaged in formal treatment
      for the first time.

PMID- 12201660
TI  - School injury trends.
AB  - This article presents data gathered between 1985 and 2000 from nine public
      schools in a Midwestern suburban school district. Data were compiled from routine
      documentation on health office logs and incident reports when students entered
      the health offices with a first-aid need. The purpose of the article is to
      demonstrate the value of the collection and analysis of injury data as a part of
      the school nurse's role and provide some samples of injury data that can be used
      for comparison purposes. First aid is the most frequent reason to see the school
      nurse and is an important function. Student injuries can cause absenteeism that
      interferes with student academic success. Whether the school nurse delegates or
      directly provides first aid, it is important to collect and analyze information
      about school injuries to plan injury prevention strategies when appropriate.

PMID- 12201661
TI  - Child and adolescent mental health web resources.
AB  - There are many Web resources for health professionals seeking guidance to meet
      the mental health needs of their clients. Some of those resources are
      specifically designed for professionals working in schools. School nurses
      participate in assessment teams and contribute to individual education plans to
      enable students with mental health needs to achieve academic success. Mental
      health issues in a school setting involve preventive care, as well as providing
      and advocating for an environment and policies that promote healthy students and
      school employees. This article identifies valid and reliable mental health Web
      resources for school nurses.

PMID- 12201662
TI  - Professional development and appraisal system for school nurses.
AB  - Dissatisfied with current school nurse evaluation instruments, school nurse
      administrators sought to develop an appraisal system that would emphasize the
      professional role of the school nurse and provide a means to enhance individual
      practice. The newly revised Standards of Professional School Nursing Practice and
      the creation of a state teacher evaluation model presented the opportunity to
      produce an instrument that could be adapted within the educational setting for
      school nursing practice. The appraisal system included not only the methods to
      evaluate practice, but the means to involve the individual school nurse through
      goal setting. The process also included a structured intervention plan that
      facilitated remediation. This article describes the development of the appraisal
      system, the components, and the implementation of an evaluation system for school
      nurses.

PMID- 12201663
TI  - Beat the heat: managing heat and hydration in marching band.
AB  - Marching band students are athletes who practice outdoors under conditions that
      expose them to dehydration, heat exhaustion, and sunstroke. They suffer these
      heat-related injuries because breaking formation frequently to adequately hydrate
      is impractical. This project developed educational materials alerting the
      students and the director to heat-related illnesses and tested a simple method of
      fluid replacement that could be used during practice. A Heat Index chart was
      adapted to identify hazardous conditions; fluid intake recommendations were made
      based on the Heat Index. Students purchased a water bottle housed in an insulated
      belt that was worn during all outdoor rehearsals. Because water was readily
      available, the students were able to drink the necessary fluids without
      interrupting the rehearsal. These bottles have been used successfully for 3
      years. Based on limited subjective data, the students reported feeling better,
      their mental acuity improved, and rehearsals were more productive. This article
      examines the effects of heat on the body and reports on a practical solution that
      has been found to protect marching band members from heat-related stress.

PMID- 12201664
TI  - Research in school nursing.

PMID- 12201665
TI  - When biology bursts into the clinic: stem cells and their potential.

PMID- 12201666
TI  - Novel diagnostic and therapeutic approaches to the diabetic retinopathy.
AB  - Diabetic retinopathy is a common cause of vision loss in industrialized countries
      and it is now evident that adequate screening protocols can identify the disease
      at an earlier, more treatable stage. Novel imaging techniques and therapeutic
      strategies, developed during the past few years and critically reviewed in this
      paper, may not only increase the standard quality of actual eye care but may also
      improve access to ophthalmological examinations and compliance with the eye care
      guidelines for all diabetic patients.

PMID- 12201667
TI  - Dangerous thrombophilic states and internal pathologies: 3 cases of thrombosis of
      the abdominal veins.
AB  - Thrombosis of the abdominal veins is a rare clinical condition which can be
      assimilated with the more frequent localization of deep venous thrombosis of the
      lower limbs. In the last few years great attention has been paid to possible risk
      factors for thrombosis of the abdominal veins. Two risk factors that have been
      identified are the presence of internal diseases and congenital and/or acquired
      abnormalities of haemostasis. The authors describe 3 clinical cases (splenic and
      portal thrombosis due to congenital thrombophilia, Budd-Chiari syndrome, portal
      cavernoma consequent to ovarian neoplasia) with different etiopathogenesis to
      show how this apparently rare condition is today more frequently encountered and
      easier to recognize. In the presence of thrombosis of major venous structures the
      search and the identification of intrinsic internal risk factors and of
      congenital and acquired thrombophilic disorders remains of great importance.
      Screening for thrombophilia includes blood C and S proteins, AT III,
      homocysteine, Leiden mutation of the factor V gene, G20210A mutation of the
      prothrombin gene, antiphospholipid antibodies. The presence of one or more of
      these risk factors allows the identification of the cases of portal thrombosis
      (EHPVO) responsible for about 10% of all the cases of portal hypertension,
      without cirrhosis or other hepatic lesions. The primary diagnostic procedure
      however remains color-Doppler ultrasonography which represents the most simple
      and the cheapest diagnostic investigation for the study of the portal and
      suprahepatic vein system, but it's strictly operator dependent.

PMID- 12201668
TI  - Predictive indexes of nocturnal desaturation in COPD patients not treated with
      long term oxygen therapy.
AB  - Nocturnal oxygen desaturation during the sleep is very frequent in patients
      affected by chronic obstructive pulmonary disease (COPD). Hypoventilation, rather
      than sleeping apnea, is commonly considered as the most relevant factor in the
      onset of nocturnal oxygen desaturation. On this topic, the Authors have carried
      on a study on the nocturnal hypoxemia in 70 hospitalized COPD patients with a
      mean FEV1% of 40 +/- 21 and a mean PaO2 of 67.7 +/- 6.1. Anthropometric features
      (sex, age, body mass index) and functional respiratory parameters (FEV1, FEV1/VC,
      PaO2, PaCO2, SaO2, pH) were considered. Moreover all the patients were
      monitorized with transcutaneous pulse oxymetry, while breathing environmental
      air, in nighttime. Mean oxyhemoglobinic nocturnal saturation (SaO2 noct.%),
      minimum registered value of nocturnal SaO2 (min SaO2 noct.%) and the minutes of
      nighttime SaO2 < or = 90% and < or = 85% (tSaO2 < or = 90% e < or = 85%) were
      considered. Fiftyfour patients (77.15%) were nocturnal desaturating (NOD),
      whereas 16 (22.85%) were not desaturating (nNOD). A statistically significant
      difference was found between the two groups as to the values of FEV1 (p < 0.05),
      PaCO2, pH, SaO2 noct.%, minimum SaO2 noct.% and tSaO2 < or = 90% and < or = 85%
      (p < 0.0001). A statistically significant correlation was found between tSaO2 <
      90% and BMI (r = 0.44), PaCO2 (r = 0.48) and pH (r = -0.44), as well as between
      tSaO2 < 85% and PaCO2 (r = 0.57) and pH (r= -0.50), between SaO2 noct.% and BMI
      (r = -0.45), PaCO2 (r = -0,50), FEV1 (r = 0.44) and pH (r = 0.46) and finally
      between minimum SaO2 noct.% and PaCO2 (r = -0.47) was found. Eighty percent of
      the NOD patients had PaO2 < 75 mm Hg and PaCO2 > 44 mm Hg. All the patients with
      PaCO2 > 50 mm Hg were NOD. In conclusion, all COPD subjects with FEV1 < 49% and
      daytime PaO2 > 60 mm Hg, particularly when associated to elevated PaCO2 values
      and high BMI, should undergo a nocturnal pulse oxymetry in order to identify
      possible nocturnal desaturations. In these patients reduced FEV1, high BMI and/or
      elevated PaCO2 appear to be predictive indexes of nocturnal desaturation. A PaCO2
      > 50 mm Hg is highly indicative for a nocturnal oxygen desaturation.

PMID- 12201669
TI  - Sentinel node role in breast cancer surgery.
AB  - Radical surgery of breast cancer includes lymphadenectomy of axilla as well as
      the dissection of the neoplastic tissue. However recently many works have raised
      doubts on the opportunity of performing routinary axillary dissection, which
      elevates morbidity risk, in absence of axillary metastases. However,
      unfortunately, information on axillary lymph node pathology, is not available
      with any other technique excluding complete dissection and istopathological
      examination. Sentinel node technique is a new methodology that consents
      evaluation of lymph node status in the operating theatre. It allows the surgeon
      to judge on the opportunity of carrying out the lymphadenectomy or not.

PMID- 12201670
TI  - Exposure to global system for mobile communication (GSM) cellular phone
      radiofrequency alters gene expression, proliferation, and morphology of human
      skin fibroblasts.
AB  - Human skin fibroblasts were exposed to global system for mobile communication
      (GSM) cellular phone radiofrequency for 1 h. GSM exposure induced alterations in
      cell morphology and increased the expression of mitogenic signal transduction
      genes (e.g., MAP kinase kinase 3, G2/mitotic-specific cyclin G1), cell growth
      inhibitors (e.g., transforming growth factor-beta), and genes controlling
      apoptosis (e.g., bax). A significant increase in DNA synthesis and intracellular
      mitogenic second messenger formation matched the high expression of MAP kinase
      family genes. These findings show that these electromagnetic fields have
      significant biological effects on human skin fibroblasts.

PMID- 12201671
TI  - Verapamil reverts resistance to drug-induced apoptosis in Ki-ras-transformed
      cells by altering the cell membrane and the mitochondrial transmembrane
      potentials.
AB  - We have previously shown that in vivo ras-transformed cell lines display natural
      doxorubicin resistance compared with the normal cells and that such resistance is
      accompanied by a plasma membrane depolarization. In this article we first extend
      the analysis of doxorubicin effect to other ras-transformed cell lines, which are
      characterized by an increasing degree of malignant phenotype. Rat thyroid ras
      transformed cells are markedly resistant to doxorubicin and the degree of drug
      resistance correlates with the degree of cell malignancy. The lower amount of
      drug accumulated inside the malignant and resistant cells is a consequence of
      their constitutive depolarized membrane potential and may account for their lack
      of drug-induced apoptosis. Verapamil, a known modulator of drug resistance, is
      able to decrease the resistance of all the malignant cell lines, initially
      causing a higher incorporation of doxorubicin as a consequence of its ability to
      hyperpolarize the membrane potential. In resistant cells, verapamil is also able
      to alter the mitochondrial membrane potential allowing apoptosis. In conclusion,
      these studies demonstrate that ras transformation induces the natural resistance
      to doxorubicin of the malignant cells. We suggest that the most malignant and
      resistant cells, of metastatic origin, could be preferentially destroyed by
      manipulation of their membrane properties, and we confirm the possibility of
      overcoming drug resistance by the administration of verapamil also in P-gp170
      nonexpressing cells.

PMID- 12201672
TI  - Pigmentation in melanomas: changes manifesting underlying oncogenic and metabolic
      activities.
AB  - Changes in pigmentation are frequently encountered in primary and metastatic
      melanocytic lesions. Pigmentation is determined by the activity of tyrosinase
      (TYR), the rate-limiting enzyme in melanin synthesis. Tyrosinase activity can be
      modulated at the genetic and/or epigenetic level. In this commentary I suggest
      that pigmentation can serve as an indicator for genetic and metabolic changes as
      follows. In TYR-negative, amelanotic melanomas cells, downregulation of TYR and
      other melanocyte-specific gene expression is likely to be mediated by dominantly
      acting oncogenes with impact on the transcriptional activity of the melanocyte
      specific transcription factor Mitf. Ras and c-myc, shown to be active and
      upregulated in subclasses of melanoma tumors, have the potential to induce these
      changes. TYR-positive highly pigmented melanoma tumors are likely to reside in
      aerobic, well-vascularized microenvironment. In contrast, hypo- or amelanotic TYR
      positive lesions suffer from reduced TYR activity due to an acidified
      microenvironment. These lesions might have encountered anaerobic conditions, and
      have adapted to the reduced oxygen by enhanced glycolysis, leading to
      extracellular acidification and activation of V-ATPase.

PMID- 12201673
TI  - Inhibition of mouse skin tumor promotion by anti-inflammatory diarylheptanoids
      derived from Alpinia oxyphylla Miquel (Zingiberaceae).
AB  - Alpinia oxphylla Miquel, which belongs to the ginger family (Zingiberaceae), has
      been used in Oriental herbal medicine. Our recent studies have revealed that the
      methanolic extract of A. oxyphylla suppresses mouse skin tumor promotion and
      induces apoptosis in cultured human promyelocytic leukemia cells. In the present
      work, we have assessed effects of yakuchinone A and yakuchinone B, phenolic
      diarylheptanoids derived from A. oxyphylla, on 12-O-tetradecanoylphorbol-13
      acetate (TPA)-induced inflammation and epidermal ornithine decarboxylase (ODC)
      activity as well as on skin tumor promotion in female ICR mice. Thus, topical
      application of 2 or 6 micromol of the diarylheptanoids prior to each topical dose
      of TPA significantly ameliorated 7,12-dimethylbenz[a]anthracene-initiated mouse
      skin tumor formation. In parallel with suppression of tumor promotion, topically
      applied yakuchinone A and B markedly inhibited TPA-induced epidermal ODC activity
      and ODC mRNA expression. In another experiment, yakuchinone A and B reduced
      production of tumor necrosis factor-alpha in TPA-stimulated mouse skin.
      Furthermore, both compounds inhibited the TPA-induced expression of
      cyclooxygenase-2 at both transcriptional and translational levels. These findings
      indicate that pungent diarylheptanoids from A. oxyphylla Miquel have an antitumor
      promotional activity that might be related to their anti-inflammatory properties.

PMID- 12201674
TI  - Synergistic enhancement of the antitumor effect of taxol by the bioreductive
      compound NLCQ-1, in vivo: comparison with tirapazamine.
AB  - The antitumor effect of taxol was investigated in combination with the
      bioreductive compounds NLCQ-1 or tirapazamine (TPZ), in vivo. The EMT6/BALB/c and
      SCCVII/C3H murine tumor models were used. All drugs were given by IP injection:
      NLCQ-1 at 10 mg/kg (28% of its LD50), TPZ at 30 or 23 mg/kg (38% or 28% of its
      LD50, respectively), and taxol up to 25 mg/kg. Dose modification factors (DMF)
      were calculated at the optimal administration intervals for potentiation of taxol
      by NLCQ-1/TPZ, by using the in vivo-in vitro assay as the endpoint. Bone marrow
      toxicity studies were performed in parallel by using a modified CFU-GM assay. A
      schedule-dependent potentiation of taxol was observed with either hypoxic
      cytotoxin and in both tumor models. The percentage of tumor cells, P, that were
      killed beyond additivity was 59.2 and 29.5 when NLCQ-1 was administered 1-3 h
      after, and TPZ 3 h before taxol, respectively, in the EMT6/ BALB/c model. The P
      values in the SCCVII/C3H model were 31.0 and 24.6 for NLCQ-1 and TPZ,
      respectively, when either of them was administered ca. 2 h after taxol. At the
      above time schedules, therapeutic indexes [ThI = DMF(T)/DMF(BM), where DMF(T) and
      DMF(BM) are the DMF values for the antitumor effect and bone marrow toxicity,
      respectively] of 2.5 and 2.0 were obtained by NLCQ-1 in the EMT6 and SCCVII
      tumors, respectively, whereas a ThI of 1.2 was obtained by TPZ in both type of
      tumors. These results suggest a potential clinical use of NLCQ-1 as a potentiator
      of taxol againstsolid tumors possessing hypoxic regions.

PMID- 12201675
TI  - Epithelioid granulomas as main clinical manifestation at the outset of non
      Hodgkin's lymphoma: report of two cases.
AB  - This article describes two cases of malignant lymphoma in which the finding of a
      striking epithelioid granulomatosis was the main clinical manifestation at the
      outset of the patients' history. Despite some suggestive clinical and laboratory
      data, the final diagnosis of lymphoproliferative disorder was made only after
      repeated histological studies in both patients. Although the association between
      a severe granulomatous reaction and a B-cell neoplasm is rare, the latter should
      be taken into account as a possible primary disease. The pathogenetic mechanisms
      postulated by the literature as the cause of granulomatous reactions in
      lymphoproliferative disorders are reported and discussed in relation to the two
      cases.

PMID- 12201676
TI  - Dose and timing of total-body irradiation mediate tumor progression and
      immunomodulation.
AB  - The major goal of this study was to examine the effects of total-body irradiation
      (TBI) on lung carcinoma progression and determine if changes in tumor growth
      could be correlated with radiation-induced alterations of immune system
      parameters. Lewis lung tumor cells were injected subcutaneously into syngeneic
      C57BL/6 mice that had been irradiated with a single 3.0 Gy dose of gamma-rays
      (60Co) at four time points either before or after tumor cell implantation.
      Subsequently, a second group of mice was irradiated 2 h prior to tumor injection
      with sequential doses of gamma-rays (0.46-2.66 Gy range). Assays were performed
      on blood and spleen from mice euthanized 16 days postimplantation. Tumor growth
      was consistently slower regardless of the timing of radiation exposure. However,
      dose of radiation influenced tumor growth delay. The preirradiated tumor-bearing
      mice had high CD4/CD8 T lymphocyte ratios along with increasing percentages of
      NKT cells in the blood supply with dose. Tumor-induced immunomodulation was also
      present, as evidenced by splenomegaly, low proliferative response to mitogens,
      and decreased spontaneous blastogenesis of leukocytes within the blood compared
      with normal values (P < or = 0.01). Anemia and thrombocytopenia were not observed
      with either tumor presence or irradiation. The present study demonstrates that a
      modest dose of TBI prior to tumor cell implantation resulted in a beneficial
      antitumor effect. A selective radiation-induced depletion of CD8+ T lymphocytes
      and changes in NKT cell percentages, correlated with findings from cytotoxicity
      assays, were indicative of a protumoricidal immune environment.

PMID- 12201677
TI  - Characterisation of municipal solid waste and its recyclable contents of
      Guangzhou.
AB  - Waste characteristics are essential data for waste disposal facilities planning
      and waste management policy formulation. However, waste composition studies are
      rarely carried out in mainland Chinese cities and even when it does, the
      methodologies used are not stringent. A year-long field survey on the physical
      components of waste and the recyclable in the waste stream has been conducted in
      Guangzhou to fill the information gap and to provide further experience for waste
      characterization study in mainland China. It was found that the ash content in
      the waste stream has decreased considerably. But the proportion of plastic
      materials in the waste stream has increased and is now comparable to its more
      urbanized cities. Although this lends support to the recent controls on expanded
      polystyrene food containers implemented by the Guangzhou environmental protection
      bureau, more detailed analysis shows that the focus should not only be on
      disposable food containers, but also on film plastic waste. Furthermore, the
      abundance of composite materials in the waste stream solicits attention from the
      waste management authority to step up the monitoring of their generation pattern
      and to consider imposing control measures.

PMID- 12201678
TI  - Comparison of methods used in the collection of source-separated household waste.
AB  - The efficiencies of four different waste collection methods were compared by
      modelling the collection of source-separated household waste in the Helsinki
      region, Finland. Efficiency was assessed on the basis of system costs, fuel
      consumption, working hours and recovery rates. The study included paper,
      biowaste, energy waste and mixed waste produced in households. Both separation of
      new types of recyclables and increasing the coverage of separate collection
      increased the costs of household waste collection independently of the collection
      method studied. Methods in which several types of waste are collected
      simultaneously increased the efficiency of waste collection. High participation
      rates and separation efficiencies reduced the costs of waste collection.

PMID- 12201679
TI  - Recycling for all: preliminary criteria for the design of disability-friendly
      receptacles.
AB  - The design of current waste bins, paper and bottle banks presents barriers for
      disabled and elderly persons, as pointed out by several Danish studies. In
      drawing up design criteria for the development of receptacles to be usable by
      persons with disabilities and senior citizens it is essential to be aware of the
      problems caused by different types of disability as well as old age. On the basis
      of general user requirements, preliminary criteria for the design of disability
      friendly receptacles are proposed. In collaboration with a collecting agent,
      current receptacles modified in accordance to the preliminary design criteria
      will be tested in pilot studies in three selected housing estates in the
      municipalities of Frederiksberg and Copenhagen. It is the authors' hope that the
      testing of the modified receptacles will result in achieving more efficient
      source separation not only for disabled and elderly persons, but for all user
      groups.

PMID- 12201680
TI  - Regional shipping strategy assessment based on installing a refuse-derived-fuel
      process in a municipal incinerator.
AB  - The rising prices of raw materials and the concerns of energy recovery have
      resulted in an increasing interest in processing the waste streams. In recent
      years, a number of credible surveys have shown that recycling and waste-to-energy
      processes appear to work well together. Compatibility exists for several reasons
      related to economic, environmental, political, and social aspects. However, the
      regional impacts of installing a centralised refused-derived fuel (RDF) process
      prior to waste-to-energy facilities remain unclear due to the inherent complexity
      of solid waste composition, generation rate, energy and material recovery goals,
      and the existing shipping patterns. This paper illustrates a thorough evaluation
      for a RDF pilot study from both quantitative and qualitative aspects. Such a
      process, consisting of the standard unit operations of shredding, magnetic
      separation, trommel screening, and air classification, might be useful for
      integrating the recycling and presorting efforts with a large-scale municipal
      incinerator in a region. A series of sampling and analyses of the waste streams
      were performed in Taipei County, Taiwan in order to characterise its potentials
      for recycling. Based on the proper estimation of solid waste generation, the goal
      programming modelling analysis not only focuses on an evaluation of how the waste
      inflows with different rates of generation, physical and chemical compositions,
      and heating values in the service areas can be processed by a centralised RDF
      facility to meet both the energy recovery and throughput requirements in
      different municipal incinerators but also indicates the optimal shipping pattern
      associated with several incinerators due to such an installation in a regional
      sense. A case study designed to explore the regional impacts on shipping patterns
      in the southwestern of Taipei County, Taiwan verifies the application potential
      of such a planning methodology.

PMID- 12201681
TI  - Co-combustion of shredder residues and municipal solid waste in a Swedish
      municipal solid waste incinerator.
AB  - Incinerating automotive shredder residue (ASR) in order to increase the recovery
      from end of life vehicles (ELVs) is an attractive option when recycling this
      material. In this study, incineration combined with energy recovery, was
      investigated. The incineration experiments, where 20% shredder residue (SR) was
      burnt with conventional municipal solid waste (MSW), were conducted in a full
      scale MSW horizontal grate incinerator. Measurements were made before, during and
      after the incineration. The results showed some minor increases in the emission
      levels of raw gases sampled after an electrostatic filter, but almost no
      significant differences when sampled after a wet scrubber. An increased level of
      'non-toxic' metals was detected within the bottom ash. It was concluded that
      refined SR, in small quantities, is suitable to add to MSW.

PMID- 12201682
TI  - The potential for adding plastic waste fuel at a coal gasification power plant.
AB  - Plastics wastes from a municipal solid waste plant have a high energy content
      which make it an interesting option for co-processing with coal. The potential
      for adding plastic waste to a coal fired Texaco IGCC (Integrated Gasification
      Combined Cycle) power station is examined. The resulting efficiency increases due
      to the improved gasification qualities of plastic over coal. For the overall
      economics to be the same as the coal only case, the maximum amount that the power
      station can afford to spend on preparing the plastic waste for use is similar to
      the assumed coal cost, plus the avoided landfill cost, minus the transport cost.
      The location of the power station plays a key role, since this has an effect on
      the transport costs as well as on the landfill charges. The sensitivity of the
      economics of co-processing plastic waste with coal for a variety of power station
      operational parameters is presented.

PMID- 12201683
TI  - Utilisation of waste nitrocellulose powders and environmental pollution in their
      destruction.
AB  - The composition of major types of waste powders and pollution during their long
      term storage in military storehouses are shown. An analysis of the powder related
      problems and the types of their recycling and utilisation is proposed. The
      gaseous products released from incineration of two major types of powder under
      atmospheric pressure were measured. It is proposed to utilise the powders through
      processing in polymer mixtures for the production of paint materials. The
      coatings made thereof have standard characteristics with self-extinguishing and
      low-flammability-point properties. A diagram of installation for waste powder
      processing by wasteless technology is shown.

PMID- 12201684
TI  - Optimisation of industrial wastes reuse as construction materials.
AB  - This study concerns the reuse of two inorganic wastes, foundry residues and fly
      ashes from municipal solid waste incineration, as "recycled aggregate" in
      concrete production. This kind of reuse was optimised by waste treatment with the
      following steps: waste washing with water; waste stabilisation-solidification
      treatment with inorganic reagents; final grinding of the stabilised waste after
      curing for about 10-20 days. Both the treated wastes were reused in concrete
      production with different mix-designs. Concrete specimens were characterised by
      means of conventional physical-mechanical tests (compression, elasticity modulus,
      shrinkage) and different leaching tests. Experimental results showed that a good
      structural and environmental quality of "recycled concrete" is due both to a
      correct waste treatment and to a correct mix-design for concrete mixture.

PMID- 12201685
TI  - Utilisation of bottom ash in road construction: evaluation of the environmental
      impact.
AB  - France incinerates about 40% of its municipal solid waste (MSW), producing 2.7
      million tons of bottom ash annually. Utilisation of bottom ash (BA) is encouraged
      in France but strictly regulated. Only bottom ash meeting specific criteria and
      produced in accordance with a quality assurance plan can be used in roadbeds and
      embankments. In order to evaluate the environmental impact of BA used in road
      construction under real conditions, two road sections were built: one containing
      a sub-layer of BA and the other, constructed using only natural gravel to serve
      as a reference. Water percolating through each roadbed was collected and sampled
      periodically over three years. Analysis of the samples shows minimal leaching of
      pollutants from BA. The results are encouraging and indicate that BA utilisation
      can be safe and can have an environmental impact no greater than that of natural
      materials.

PMID- 12201687
TI  - Hospital waste management in Brazil: a case study.
AB  - The evaluation of the current definition, classification and quantification of
      hospital waste being carried out by hospitals in different countries is extremely
      important to avoid improper waste management practices. In this work, the waste
      management from a 400-bed Brazilian hospital which generates about 386 kg per day
      of hospital waste was studied. The generation rate of just over one kg per bed
      per day was considered small, although more than 50% of the waste from non
      isolation wards consisted of food waste. It was also interesting to note that the
      highest generation rate per patient per day was found in private rooms and the
      lowest rate in the public ones. The waste practices used in this hospital are
      discussed in terms of current Brazilian legislation.

PMID- 12201686
TI  - Utilisation of bottom ash in road construction: a lysimeter study.
AB  - The incineration of municipal solid waste (MSW) results in the annual production
      of 2.7 million tons of bottom ash in France. Utilisation of bottom ash in road
      construction is encouraged in France but strictly regulated. Because the
      incinerator residues contain enriched concentrations of metals and salts,
      particular attention must be focused on the potential environmental problems. In
      the present study, a laboratory tool (lysimeter) has been developed to reproduce
      the conditions of bottom ash utilisation and to study their environmental impact
      via the percolates collected at the bottom of the lysimeter. Four lysimeter
      experiments were conducted in order to study reproducibility, as well as the
      influence of water flow rate and pressure on the composition of the percolates.
      The lysimeter experiments have been then compared with the utilisation of bottom
      ash under real conditions (two experimental road sections). The comparison of
      results of lysimeter test and those measured after performing the French standard
      leach test (AFNOR NF X31-210) shows a recovery of 89% for the chlorides and
      between 30 and 35% for the sulfates. This indicates that almost all chlorides
      have been dissolved, contrary to the sulfates, which are less soluble.

PMID- 12201688
TI  - Study for reclamation of land occupied by solar evaporation pond at UCIL, Bhopal,
      India.
AB  - Solar Evaporation Ponds (SEP) were used by Union Carbide India Limited (UCIL),
      Bhopal for storage of wastewater containing high concentrations of inorganic
      chemicals especially chlorides. Area occupied by the SEPs had to be recovered due
      to closure of the plant. A prerequisite to the reclamation of the SEP area is a
      study of adjoining soil and groundwater, which may be contaminated due to
      possible leakage in the pond. Surface soil, subsurface soil and groundwater
      samples were collected and analysed. The electrical conductivity method was
      employed inside the pond to test for leak in the geo-membrane liner. This was
      further confirmed by physically checking the liners. Based on the wet period,
      total rainfall and evaporation rate of the region, drying of remaining wastewater
      by spreading in dry ponds followed by pond dismantling was scheduled.

PMID- 12201689
TI  - Lateral gas transport in soil adjacent to an old landfill: factors governing gas
      migration.
AB  - Field experiments investigating lateral gas transport in soil adjacent to an old
      landfill in Denmark during a one-year period were conducted. A significant
      seasonal variation, with low concentrations of methane and high concentrations of
      carbon dioxide in the summer, caused by methane oxidation was observed. There was
      a good correlation between pressure above the barometric pressure and the methane
      concentration in the soil, indicating that advective flow was the controlling
      process. This was confirmed by calculations. Diurnal measurement during a drop in
      barometric pressure showed that lateral migration of landfill gas was a very
      dynamic system and the concentrations of LFG at a specific place and depth
      changed dramatically within a very short time. The experiments showed that change
      in barometric pressure was an important factor affecting gas migration at the
      Skellingsted landfill in Denmark.

PMID- 12201690
TI  - Lateral gas transport in soil adjacent to an old landfill: factors governing
      emissions and methane oxidation.
AB  - Field investigations of lateral gas transport and subsequent emissions in soil
      adjacent to an old landfill in Denmark have been conducted during a one-year
      period. A significant seasonal variation in the emissions with high carbon
      dioxide and low methane fluxes in the summer (May to October) was observed. This
      was attributed to methane oxidation. Diumal measurements during a drop in
      barometric pressure showed that the fluxes of landfill gas changed dramatically
      within a very short time. The concentrations and the soil moisture content in the
      upper part of the soil profile had significant influence on the fluxes, as did
      the distance from the landfill border, temperature, barometric pressure and the
      pressure gradient. Statistical analyses proved that soil moisture described the
      largest part of the variation. No methane at all emitted during the summer.
      Calculations and isotope analyses showed that very high fractions of the
      laterally migrating methane were oxidised.

PMID- 12201691
TI  - Design of landfill daily cells.
AB  - The objective of this paper is to study the behaviour of the landfill soil-to
      refuse (S/R) ratio when size, geometry and operating parameters of the daily cell
      vary over realistic ranges. A simple procedure is presented (1) for calculating
      the cell parameters values which minimise the S/R ratio and (2) for studying the
      sensitivity of this minimum S/R ratio to variations in cell size, final refuse
      density, working face length, lift height and cover thickness. In countries where
      daily soil cover is required, savings in landfill space could be realised
      following this procedure. The sensitivity of minimum S/R to variations in cell
      dimensions decreases with cell size. Working face length and lift height affect
      the S/R ratio significantly. This procedure also offers the engineer an
      additional tool for comparing one large daily cell with two or more smaller ones,
      at two different working faces within the same landfill.

PMID- 12201706
TI  - Complexation of small molecules by open-ended resorcarene hosts.
AB  - [structure: see text] Sterically hindered tetraaminomethylated resorcarenes form
      inclusion complexes in CDCl(3) with acetonitrile and acetaldehyde, which are
      kinetically stable on the NMR time scale at 233 K.

PMID- 12201707
TI  - Diastereocontrol by a hydroxyl auxiliary in the synthesis of pyrrolidines via
      radical cyclization.
AB  - [reaction: see text] Organoselenium precursors of 3-aza-5-hexenyl radicals
      carrying a 1-hydroxyalkyl group in the 2-position were prepared by addition of
      organometallic reagents to N-allyl-2-aziridinecarbonitrile, reduction of the
      resulting aziridine ketone, and regioselective benzeneselenol ring opening of the
      aziridine. Reductive radical cyclization was highly selective, affording the
      corresponding trans-2,4-disubstituted pyrrolidine (cis/trans ca. 1/10) as the
      major diastereomer. Recrystallization afforded material that was substantially
      more enriched in the trans isomer (cis/trans < 1/25).

PMID- 12201708
TI  - Synthesis of 7-substituted farnesyl diphosphate analogues.
AB  - [structure: see text] Six farnesyl diphosphate analogues modified in the central
      isoprene unit have been prepared via our stereoselective vinyl triflate-mediated
      route to isoprenoids. The 7-allyl compound 6 is a modest inhibitor of mammalian
      protein-farnesyl transferase, but surprisingly the other five analogues are
      effective alternative substrates for this enzyme.

PMID- 12201709
TI  - New palladium carbene catalysts for the Heck reaction of aryl chlorides in ionic
      liquids.
AB  - [reaction: see text] The Heck reaction of aryl chlorides was investigated in the
      presence of defined monocarbenepalladium(0) complexes. Activated and nonactivated
      aryl chlorides provide the corresponding cinnamic esters and stilbenes in
      (n)Bu(4)NBr as a ionic liquid in good to excellent yields.

PMID- 12201710
TI  - Synthesis of annulated gamma-carbolines by palladium-catalyzed intramolecular
      iminoannulation.
AB  - [reaction: see text] A variety of N-substituted 2-bromo-1H-indole-3
      carboxaldehydes incorporating an alkyne-containing tether on the indole nitrogen
      have been converted to the corresponding tert-butylimines, which have been
      subjected to palladium-catalyzed intramolecular iminoannulation, affording
      various annulated gamma-carbolines in excellent yields.

PMID- 12201711
TI  - Nagahamide A, an antibacterial depsipeptide from the marine sponge Theonella
      swinhoei.
AB  - [structure: see text] An antibacterial depsipeptide, nagahamide A (1), has been
      isolated from the marine sponge Theonella swinhoei. Its structure was determined
      on the basis of spectral and chemical methods. Absolute configuration of amino
      acid residues was determined by Marfey's analysis, and relative stereochemistry
      of the polyketide moiety was assigned by comparison of NMR data with those of a
      model compound.

PMID- 12201712
TI  - Synthesis and characterization of radial oligothiophenes: a new class of
      thiophene-based conjugated homologues.
AB  - [structure: see text] A series of thiophene-based homologues with an aromatic
      core surrounded by terthiophene "arms" with acetylene linkages has been
      synthesized by using Sonogashira coupling methods. The homologues were
      investigated spectroscopically in solution and in the solid state. They display
      extended pi-conjugation through the aromatic core that affects the strong
      emission and redox properties.

PMID- 12201713
TI  - Medium ring ethers by ring expansion-ring contraction: synthesis of lauthisan.
AB  - [reaction: see text] A new general method for the construction of medium ring
      ethers has been developed. This involves the ring expansion of halo-O,S-acetals
      followed by a Ramburg-Backlund ring contraction reaction with concomitant
      extrusion of the sulfur atom. This methodology has been utilized for the
      synthesis of cis- and trans-lauthisan.

PMID- 12201714
TI  - Highly enantioselective reformatsky reaction of ketones: chelation-assisted
      enantioface discrimination.
AB  - [reaction: see text] Highly enantioselective Reformatsky reaction of ketones was
      accomplished using cinchona alkaloids as chiral ligands. Chelation with the sp(2)
      nitrogen adjacent to the reactive carbonyl center contributed the enantioface
      discrimination for the high enantioselectivities.

PMID- 12201715
TI  - A nitro-hunsdiecker reaction: from unsaturated carboxylic acids to nitrostyrenes
      and nitroarenes.
AB  - [reaction: see text] The nitrodecarboxylation of aromatic alpha,beta-unsaturated
      carboxylic acids and ring-activated benzoic acids can be achieved using nitric
      acid (3 equiv) and catalytic AIBN (2 mol %) in MeCN. From the effect of various
      additives, the nitrodecarboxylation is postulated to involve the generation of an
      acyloxy radical RCO(2)(*) by a NO(3)(*) radical followed by attack of a NO(2)(*)
      radical.

PMID- 12201716
TI  - Synthesis of enantiopure dihydropyranones: aldol-based ring expansion of
      dihydrofurans.
AB  - [reaction: see text] The stereoselective Birch reduction of 3-methyl-2-furoic
      acids using a readily available chiral auxilairy is described; by coupling this
      process to an oxidative cleavage/aldol ring closure sequence we were able to
      produce highly functionalized and enantiopure dihydropyranones in high yield.
      This sequence has ample flexibility built into it, either by the use of different
      electrophiles during reductive alkylation or by subsequent derivatization of the
      dihydropyranone after ring expansion.

PMID- 12201717
TI  - Synthesis and characterization of three novel [60]fullerene derivatives toward
      self-assembled nanoparticles through interaction of hydrogen bonding.
AB  - [structure: see text] Three novel fullerene derivatives bearing a 2,6
      bis(acylamino) pyridine unit as a hydrogen bonding motif displaying a
      dimerization tendency were synthesized and characterized by the cycloaddition
      reaction of alkyl azide to [60]fullerene. An SEM image of the dimerization system
      of compound 1 indicated spherical particles having a mean diameter of 15 nm with
      a rather narrow size distribution.

PMID- 12201718
TI  - Synthesis of O-glycolyl-linked neuraminic acids through a spirocyclic
      intermediate.
AB  - [reaction: see text] The neuraminic acid derivative 5 is readily converted in
      several steps to the neuraminic acid dimer 12, linked through the hydroxyl of a 5
      N-glycolyl group in an alpha-2,5 glycosidic linkage. The sequence is shown to
      proceed through a spirocyclic intermediate 9 by in situ NMR experiments. Similar
      derivatives of N-glycolylneuraminic acid (Neu5Gc), including polymers, have been
      identified from marine sources, including starfish and sea urchins, often as
      sulfated derivatives and are thought to mediate sperm-egg recognition.

PMID- 12201719
TI  - Ionic liquid acceleration of solid-phase suzuki-miyaura cross-coupling reactions.
AB  - [reaction: see text] Room-temperature ionic liquids promote various transition
      metal-catalyzed reactions in the solution phase. Here, for the first time, we
      show that these effects are translatable to solid-phase reactions. The Suzuki
      Miyaura cross-coupling of 4-iodophenol immobilized on polystyrene-Wang resin with
      various arylboronic acids was significantly accelerated by the ionic liquid 1
      butyl-3-methylimidazolium tetrafluoroborate ([bmim][BF(4)(-)]).

PMID- 12201720
TI  - Empirical model for the molar rotations of syn-2,2-dimethyl-1,3-dioxanes.
AB  - [structure: see text] A useful method for the prediction of molar rotation
      ([Phi]) of syn-2,2-dimethyl-1,3-dioxanes (acetonides) is described. A series of
      acetonides were prepared by standard methods. A simple additive relationship
      between the substituents (R, R') and molar rotation was realized.

PMID- 12201721
TI  - Intramolecular cyclization of acyl radicals onto the azido group: a new radical
      approach to cyclized lactams.
AB  - [reaction: see text] Aryl- and alkyl-derived azidoacyl radicals, generated from
      thiolesters by intramolecular homolytic substitution at the sulfur, can undergo
      five- and six-membered cyclization onto the azido moiety to give cyclized
      lactams.

PMID- 12201722
TI  - Absolute rate constants for water protonation of 1-(3-benzoylphenyl)alkyl
      carbanions.
AB  - [reaction: see text] Efficient photodecarboxylation of (3-benzoylphenyl)alkanoic
      acids with formation of carbanions has enabled the determination of their
      protonation rate constants in water; the values obtained show that the reactivity
      toward protonation is determined by the size of the alkyl groups attached to the
      carbanion center.

PMID- 12201723
TI  - Total synthesis of luminacin D.
AB  - [reaction: see text] A highly convergent synthesis of the angiogenesis inhibitor
      luminacin D has been achieved in 13 linear steps (19 steps total, 5.3% overall
      yield) utilizing a samarium(II) iodide-mediated mixed tandem aldol/Evans
      Tishchenko reaction to construct the carbohydrate precursor. The modular
      synthetic design will allow derivatization at key positions necessary for
      biochemical mode of action studies.

PMID- 12201724
TI  - Stereoselective synthesis of highly functionalized 1,5-oxa-bridged cyclooctenes
      via a 3-oxidopyrylium-cyclopropenone acetal cycloaddition [corrected].
AB  - [reaction: see text] A [5C+2C] oxidopyrylium-cyclopropenone acetal cycloaddition
      followed by ring opening of the cyclopropane unit of the resulting adduct leads
      to highly substituted 1,5-oxa-bridged cyclooctenes containing up to four
      stereocenters. The protocol formally constitutes a [5C+3C] annulation process.

PMID- 12201725
TI  - Thiersinines A and B: novel antiinsectan indole diterpenoids from a new
      fungicolous Penicillium species (NRRL 28147).
AB  - [structure: see text] Two novel antiinsectan indole diterpenoids, thiersinines A
      (1) and B (2), along with seven known paxilline-type compounds, were isolated
      from organic extracts of a new Penicillium species (P. thiersii NRRL 28147). The
      structures of 1 and 2 were determined by analysis of 2D NMR data. Thiersinines A
      and B possess a unique spirocyclic subunit that is unprecedented in previously
      known compounds of this class. Both compounds exhibit potent activity against the
      fall armyworm (Spodoptera frugiperda).

PMID- 12201726
TI  - Cycloadditions of nonstabilized 2-azaallyllithiums with cycloheptatriene.
AB  - [reaction: see text] Transmetalation of tin-bearing cyclic imidates gave 2
      azaallyllithiums that underwent [pi6s + pi4s] cycloadditions with
      cycloheptatriene to produce tricyclic adducts, which may be useful as analogs of
      cocaine. The peri- and stereoselectivity of this process are discussed.

PMID- 12201727
TI  - Synthesis and V-ATPase inhibition of simplified lobatamide analogues.
AB  - [structure: see text] Simplified analogues of the lobatamides have been
      synthesized and evaluated for inhibition of bovine V-ATPase. The salicylate
      phenol, enamide NH, and the ortho-substitution of the salicylate ester have been
      shown to be important for V-ATPase inhibitory activity.

PMID- 12201728
TI  - 2,7-Bis(1H-pyrrol-2-yl)ethynyl-1,8-naphthyridine: an ultrasensitive fluorescent
      probe for glucopyranoside.
AB  - [structure: see text] A push-pull conjugated molecule, 2,7-bis(1H-pyrrol-2
      yl)ethynyl-1,8-naphthyridine (BPN), has been designed to bind selectively with
      octyl glucopyranoside (OGU). The BPN/OGU quadruple hydrogen-bonding complex
      adopts a rigid BPN conformation in which the proton donor (d) and acceptor (a)
      relays (daad) are resonantly conjugated through the ethynyl bridge, inducing pi
      electron delocalization, i.e., a charge transfer effect. The excellent
      photophysical properties make BPN a highly sensitive probe for monitoring
      glucopyranoside to a detection limit of approximately 100 pM.

PMID- 12201729
TI  - Intramolecular tandem Michael-type addition/aldol cyclization induced by TiCl(4)
      R(4)NX combinations.
AB  - [reaction: see text] Treatment of formyl alpha,beta-enones with a TiCl(4)-R(4)NX
      combination induces an intramolecular aldol cyclization to furnish 2-acyl-3
      halocyclohexanol with three controlled consecutive stereogenic centers. The
      reaction of bis-alpha,beta-enones with the combination provides cyclic diketones
      with high stereoselectivity via an intramolecular Michael addition reaction.

PMID- 12201730
TI  - C-H activation and palladium migration within Biaryls under Heck reaction
      conditions.
AB  - [reaction: see text] Biaryl bromides such as 1 (R=NO(2), H, OMe) undergo the Heck
      reaction to give both the expected products 3 ("retention") as well as
      "crossover" products 4 derived from a migration of Pd and net transfer of
      reactivity from one aryl ring to the other. Under the conditions used, crossover
      is increasingly favored when electron-deficient arenes are involved. Crossover
      products derived from transfer onto the pyridine ring have also been observed.

PMID- 12201731
TI  - Anionic inverse electron-demand 1,3-dipolar cycloaddition of nitrones with
      ynolates. Facile stereoselective synthesis of 5-isoxazolidinones leading to beta
      amino acids.
AB  - [reaction: see text] The inverse electron-demand 1,3-dipolar cycloaddition of
      nitrones with ynolates, followed by quenching with t-BuOH, produced substituted 5
      isoxazolidinones with good trans-selectivity. These products were easily
      converted into beta-amino acids.

PMID- 12201732
TI  - Symmetric and helical growth of polyacetylene fibers over a single copper crystal
      derived from copper tartrate decomposition.
AB  - [reaction: see text] Helical polyacetylene fibers with absolutely symmetric
      structures were prepared by polymerization of acetylene using copper tartrate as
      a catalyst. There were always only two coiled polyacetylene fibers grown on a
      single copper nanocrystal. The two coiled fibers had absolutely opposite helical
      senses but were identical in cycle number, coil diameter, coil length, coil
      pitch, and fiber diameter.

PMID- 12201733
TI  - A mild method for the formation and in situ reaction of imidoyl chlorides:
      conversion of pyridine-1-oxides to 2-aminopyridine amides.
AB  - [reaction: see text] A mild, practical, one-pot method for the generation of
      imidoyl chlorides and their subsequent in situ reaction with pyridine-1-oxides is
      described. The imidoyl chlorides were formed from the reaction of secondary
      amides with a stoichiometric amount of oxalyl chloride and 2,6-lutidine in
      CH(2)Cl(2) at 0 degrees C. Upon warming of the reaction mixture to room
      temperature in the presence of pyridine-1-oxides, a rapid conversion to 2
      aminopyridine amides was observed in moderate to excellent isolated yields.

PMID- 12201734
TI  - Directed reduction of beta-amino ketones to syn or anti 1,3-amino alcohol
      derivatives.
AB  - [reaction: see text] The reduction of beta-amino ketones with samarium(II) iodide
      has been investigated. Either the syn or anti 1,3-amino alcohols can be obtained
      as the major product due to a divergence in selectivity with different N
      protecting groups.

PMID- 12201735
TI  - Formation of the corannulene core by nickel-mediated intramolecular coupling of
      benzyl and benzylidene bromides: a versatile synthesis of dimethyl 1,2
      corannulene dicarboxylate.
AB  - [reaction: see text] A practical synthesis of dimethyl 1,2-corannulene
      dicarboxylate (5) is reported, with the final ring-forming step achieved by the
      double intramolecular nickel powder mediated coupling of benzyl and benzylidene
      bromide groups with 60% isolated yield.

PMID- 12201736
TI  - Synthetic approach to hypoxyxylerone, novel inhibitor of topoisomerase I.
AB  - [reaction: see text] A potential route to the topoisomerase I inhibitor
      hypoxyxylerone is demonstrated by a highly convergent synthesis of the penta(O
      methyl) derivative. The key step in the approach is an anionic homo-Fries
      rearrangement, little used to date in natural product synthesis and employed here
      for the first time with a dinaphthalenic substrate, to access the pentacyclic
      system of hypoxyxylerone.

PMID- 12201737
TI  - Multinuclear NMR structural characterization of an unprecedented photochromic
      allene intermediate.
AB  - [structure: see text] An o-allenyl-p-methoxyphenol intermediate (Int) was for the
      first time proved to be involved in the photochromic reaction of 2,2-di(4
      fluorophenyl)-6-methoxy-2H-1-chromene (FC). Transoid-cis (TC) and transoid-trans
      (TT) photomerocyanines and the intermediate Int are generated by UV irradiation
      of FC. Visible light converts TC and TT into Int. The monitoring of the reactions
      was carried out on the basis of (1)H, (13)C, (19)F, and (2)H NMR spectroscopy.

PMID- 12201738
TI  - A novel metal iodide promoted three-component synthesis of substituted
      pyrrolidines.
AB  - [reaction: see text] A new one-pot procedure for the synthesis of substituted
      pyrrolidine derivatives with commercially available cyclopropyl ketones,
      aldehydes, and amines by a metal iodide promoted three-component reaction was
      developed.

PMID- 12201739
TI  - Complex-induced proximity effects. Temperature-dependent regiochemical diversity
      in lithiation-electrophilic substitution reactions of N-BOC-2
      azabicyclo[2.1.1]hexane. 2,4- and 3,5-methanoprolines.
AB  - [reaction: see text] Azabicycle 4 and sec-butyllithium/TMEDA afford the C(1)
      bridgehead alpha-lithio anion at 0 degrees C. Anion quenching with carbon
      dioxide, methyl chloroformate, or DMF provide the bridgehead acid 8a (N-BOC-2,4
      methanoproline), ester 8b, or aldehyde 8c, respectively. By contrast, at -78
      degrees C these same reagents give a mixture of regioisomeric methylene and
      bridgehead anions whose quenching leads to mixtures of regioisomeric methylene
      and bridgehead acids 6a/8a, esters 6b/8b, or aldehydes 6c/8c, respectively. The
      previously unknown 3,5-methanoproline was prepared as its N-BOC methyl ester 6b.

PMID- 12201740
TI  - A convenient preparation of 2-fluoro-3-alkoxy-1,3-butadienes.
AB  - [reaction: see text] 1-Chloro-1-fluoro-2-methoxy-2-methylcyclopropane eliminates
      HCl on heating in quinoline solution above 50 degrees C to give 2-fluoro-3
      methoxy-1,3-butadiene in high yield. If an alcohol is added to the reaction then
      a 2-fluoro-3-alkoxy-1,3-butadiene is obtained in high yield. The dienes give
      smooth 4 + 2 cycloaddition reactions.

PMID- 12201741
TI  - Application of the intramolecular vinylogous Morita-Baylis-Hillman reaction
      toward the synthesis of the spinosyn A tricyclic nucleus.
AB  - [reaction: see text] A concise synthesis of the spinosyn A tricyclic nucleus 27
      has been developed by a route featuring a one-pot tandem intramolecular Diels
      Alder reaction and intramolecular vinylogous Morita-Baylis-Hillman cyclization in
      which five stereocenters in tricycle 10 are set with excellent selectivity.

PMID- 12201742
TI  - Solvent-free sonochemical preparation of ionic liquids.
AB  - [reaction: see text] An ultrasound-assisted preparation of a series of ambient
      temperature ionic liquids, 1-alkyl-3-methylimidazolium (AMIM) halides, which
      proceeds via efficient reaction of 1-methyl imidazole with alkyl halides/terminal
      dihalides under solvent-free conditions, is described.

PMID- 12201743
TI  - Biaryl synthesis from two different aryl halides with tri(2-furyl)germane.
AB  - [reaction: see text] The coupling reaction of germanium compounds with aryl
      halides has been developed. The Pd(0)-catalyzed reaction of aryl halides with
      tri(2-furyl)germane provides aryltri(2-furyl)germanes in good yield. The cross
      coupling reaction of aryltri(2-furyl)germanes with aryl halides is achieved. This
      allows facile synthesis of unsymmetrical biaryls from two different aryl halides.

PMID- 12201745
TI  - Palladium-catalyzed cross-alkynylation of aryl bromides by sodium
      tetraalkynylaluminates.
AB  - Sodium tetraalkynylaluminates (1-4), prepared from NaAlH4 and terminal alkynes,
      cross-couple with aryl bromides in the presence of Pd(0) and Pd(II) catalysts.
      The reactions take place in boiling THF or DME. The process is applicable to both
      homo- and heterocyclic aryl bromides and can be used for conversion of polybromo
      compounds into polyalkynes. The reactions are high yielding and selective, free
      of undesired homocoupling and hydrogenolysis processes. The reagents selectively
      react with the ring-bound bromine atoms but do not affect chloro, cyano,
      triflate, or ester functions.

PMID- 12201746
TI  - Electrotelluration: a new approach to tri- and tetrasubstituted alkenes.
AB  - A novel electrotelluration process is described in which a Michael addition of an
      alkyl or aryl tellurolate anion occurs onto an activated alkyne with subsequent
      trapping of a vinyl anion with electrophiles (aldehydes and ketones) other than a
      proton. This process provides an efficient regio- and stereospecific route to tri
      and tetrasubstituted alkenes. Methodologically significant examples of this
      chemistry were studied in which aryl and alkyl tellurolate anions were added to
      omega-keto alkynyl esters in a Michael reaction, and the incipient vinyl anions
      were trapped intramolecularly by the internal aldehydes. The reactive centers
      were tethered by different lengths of alkyl chains to form highly functionalized
      five-, six-, seven-, and eight-membered rings in modest to good yields.

PMID- 12201748
TI  - 30pi aromatic meso-substituted heptaphyrin isomers: syntheses, characterization,
      and spectroscopic studies.
AB  - The syntheses of new aromatic 30pi heptaphyrins either through a [5 + 2] or a [4
      + 3] acid-catalyzed condensation and oxidative coupling reactions of easily
      available and air-stable precursors are reported. The methodology followed is not
      only simple and efficient but also allows synthesis of a range of heptaphyrins
      with different heteroatoms in the core. The oxidative coupling reactions of
      modified tripyrranes 11 and tetrapyrranes 12 were found to be dependent on the
      acid concentration used and as well as the substituents present on the meso
      position. The change of meso aryl substituents in 11 and 12 to meso mesityl
      substituents gave a new heptaphyrin 18. The structural characterization has been
      done with extensive 1H and 2D NMR studies. The heptaphyrins reported here show
      rich structural diversity when the connections of the heterocyclic rings are
      altered, and accordingly, one ring and two ring inversions have been observed. By
      a judicious choice of the precursors it has been possible to control the site of
      ring inversion either in the bithiophene unit or in the tripyrrane unit.
      Theoretical calculations performed on three different heptaphyrins, 4, 5, and 17,
      also reveal that the inverted structures are approximately 35-40 kJ lower in
      energy relative to the corresponding noninverted structures. Furthermore, one of
      the heptaphyrins 10c shows the presence of two conformers in solution in the
      ratio 1:2 and no interconversion between the conformers have been observed in the
      temperature range of 343-228 K. On protonation, the aromaticity and the ring
      inversions are retained and the deltadelta values vary in the range 10.07-20.59
      ppm. The energies of the Soret maxima and the HOMO-LUMO gap vary linearly with
      the increase in pi electrons further justifying the aromatic nature of the
      heptaphyrins.

PMID- 12201747
TI  - Application of the anomeric samarium route for the convergent synthesis of the C
      linked trisaccharide alpha-D-Man-(1-->3)-[alpha-D-Man-(1-->6)]-D-Man and the
      disaccharides alpha-D-Man-(1-->3)-D-Man and alpha-D-Man-(1-->6)-D-Man.
AB  - Studies are reported on the assembly of the branched C-trisaccharide, alpha-D-Man
      (1-->3)-[alpha-D-Man-(1-->6)]-D-Man, representing the core region of the
      asparagine-linked oligosaccharides. The key step in this synthesis uses a SmI(2)
      mediated coupling of two mannosylpyridyl sulfones to a C3,C6-diformyl branched
      monosaccharide unit, thereby assembling all three sugar units in one reaction and
      with complete stereocontrol at the two anomeric carbon centers. Subsequent tin
      hydride-based deoxygenation followed by a deprotection step produces the target C
      trimer. In contrast to many of the other C-glycosylation methods, this approach
      employes intact carbohydrate units as C-glycosyl donors and acceptors, which in
      many instances parallels the well-studied O-glycosylation reactions. The
      synthesis of the C-disaccharides alpha-D-Man-(1-->3)-D-Man and alpha-D-Man-(1-
      >6)-D-Man is also described, they being necessary for the following
      conformational studies of all three carbohydrate analogues both in solution and
      bound to several mannose-binding proteins.

PMID- 12201749
TI  - Background of the Hammett equation as observed for isolated molecules: meta- and
      para-substituted benzoic acids.
AB  - Fundamental model compounds for the Hammett equation, meta- and para-substituted
      benzoic acids, were investigated by the density functional theory at the B3LYP/6
      311+G(d,p) level. Energies of 25 acids and of their anions were calculated in all
      possible conformations and from them the energies of the assumed mixture of
      conformers. Relative acidities correlated with the experimental gas-phase
      acidities almost within the experimental uncertainty, much more precisely than in
      the case of previous calculations at lower levels. Dissection of the substituent
      effects into those operating in the acid molecule and in the anion was carried
      out by means of isodesmic reactions starting from monosubstituted benzenes. Both
      effects are cooperating in the resulting effect on the acidity; those in the acid
      molecule are smaller but not negligible. They are also responsible for some
      deviations from the Hammett equation (through-resonance of para donor
      substituents) and for the weaker resonance in the acid molecule in meta
      derivatives; in the anions the inductive and resonance effects are almost equal.
      On the other hand, the cooperation of effects in the acid and in the anion makes
      the relative acidity more sensitive to electron withdrawing and is probably one
      of the reasons why the Hammett equation is so generally valid.

PMID- 12201750
TI  - Solution-state conformational study of the hevamine inhibitor allosamidin and six
      potential inhibitor analogues by NMR spectroscopy and molecular modeling.
AB  - The solution-state conformations of the hevamine inhibitor allosamidin and six
      potential inhibitor analogues were studied by various NMR spectroscopic
      techniques and molecular modeling using force field calculations. Determination
      solely of the global energy minimum conformation was found to be insufficient for
      consensus with the NMR results, and agreement between the NMR experimental data
      and the theoretical calculations was only reached by assessing the structures as
      population-weighted average conformers on the basis of Boltzmann distributions
      derived from the calculated relative energies. The conformations of the
      glycosidic linkages in the compounds were found to be similar when the sugar
      residues were the same, but differences were markedly evident otherwise and also
      for the various heterocyclic group linkages. The binding of the compounds to
      hevamine, which may also complex to chitinases in general, was assessed using
      HMQC, transfer-NOESY, and both 1-D and 2-D saturation transfer difference NMR
      experiments. Under the conditions employed, only allosamidin was implicated to be
      bound to hevamine, and then only by HMQC with the dipolar coupling-based
      experiments failing to substantiate the formation of the complex. However, the
      results are consistent with the biochemical activities of the compounds whereby
      only allosamidin has been shown to act as a competitive inhibitor.

PMID- 12201751
TI  - Control of the conformational equilibria in aza-cis-decalins: structural
      modification, solvation, and metal chelation.
AB  - A series of amino alcohol- and diamino-cis-decalins were synthesized and their
      conformational properties investigated. The equilibrium distributions of the
      conformational isomers were measured via NMR spectroscopy. The equilibrium ratios
      depend on the position of the substituents on the decalin ring system and the
      solvent. The 7-substituted 1-aza-cis-decalins are more likely to adopt the N-in
      form than the 5-substituted analogues. The N-in form is generally favored in
      nonpolar solvents, while the N-out form is favored in polar solvents.
      Complexation with LiClO4 and Et2Zn alters the equilibrium to favor the N-in
      decalin conformer. Both conformers coordinate lithium ions such that "on/off"
      conformational switching is not observed for these decalins. Comparison of the
      results with complexation studies of (-)-sparteine allows the criteria for an
      ideal "on/off" conformational switch to be defined.

PMID- 12201752
TI  - The role of aromaticity in the planarity of lumiflavin.
AB  - Ab initio MP2/6-31G(d,p) and density functional theory B3LYP/6-31G(d,p)
      calculations were performed to investigate the molecular structure of the active
      part of flavins in the oxidized and reduced forms, using lumiflavin as a model
      compound. The possible aromatic character of these systems was explored by using
      the following aromaticity indexes: nucleus-independent chemical shifts, the
      anisotropy of the magnetic susceptibility, the Bird index, and natural bond
      orbital analysis. To provide further insight, calculations on the 2+ charged
      species were also carried out. Both the MP2 and B3LYP computations predict a
      planar conformation for the oxidized form and a bent structure for the reduced
      form, in agreement with previous experience. For both the oxidized and reduced
      states, ring A is found to be the most aromatic, as expected. The calculations
      suggest that the folding in the reduced form is mainly a result of electronic
      preferences rather than steric hindrance.

PMID- 12201753
TI  - Stereoselective synthesis of dipeptide beta-turn mimetics: 7-benzyl and 8-phenyl
      substituted azabicyclo[4.3.0]nonane amino acid esters.
AB  - A stereoselective method has been developed for the synthesis of 7- and 8
      substituted dipeptide beta-turn mimetic azabicyclo[4.3.0]nonane amino acid
      esters. The allyl groups were introduced in high diastereoselectivity, controlled
      by 3-phenyl or 4-benzyl groups in pyroglutamic acid derivatives 3 or 9,
      respectively. The precursors, dehydroamino acids 7 and 13 derived from 5 or 11,
      underwent asymmetric hydrogenations with Burk's DuPHOS Rh(I)-based catalysts to
      furnish alpha-amino acid derivatives in high stereoselectivity. The resulting
      amino acids 8 and 14 were converted to the beta-turn mimetics 6,5-bicyclic
      lactams 1a-d in high yields.

PMID- 12201754
TI  - Asymmetric synthesis of (+)-negamycin.
AB  - An asymmetric synthesis of the antibiotic (+)-negamycin (1) has been achieved,
      starting from commercially available (5R,6S)-4-(benzyloxycarbonyl)-5,6-diphenyl
      2,3,5,6-tetrahydro-4H-1,4-oxazin-2-one (2). The synthesis involved the stabilized
      Wittig olefination of the lactone carbonyl group of 2 and subsequent asymmetric
      hydrogenation to generate the corresponding all-syn oxazine 4 with excellent
      diastereoselectivity. Conversion of 4 into beta-alkoxy imine 7 and subsequent
      CeCl3-promoted chelation-controlled allylation of 7 generated the corresponding
      homoallylamine 8 with good diatereoselectivity, which was readily converted into
      (+)-negamycin (1) in 25% overall yield over 11 steps.

PMID- 12201755
TI  - Stereoselective synthesis of (E)-beta-tributylstannyl-alpha,beta-unsaturated
      ketones: construction of a key intermediate for the total synthesis of
      zoanthamine.
AB  - (E)-beta-Trialkylstannyl-alpha,beta-unsaturated ketones are readily available
      from secondary propargylic alcohols via a two-step sequence involving highly
      regio- and stereoselective Pd(0)-catalyzed hydrostannation followed by mild
      oxidation (TPAP). The methodology has been applied to the synthesis of
      enantiomerically pure enone 12 which is a key intermediate for the total
      synthesis of zoanthamine, a structurally complex marine natural product.

PMID- 12201756
TI  - Amino acid bromides: their N-protection and use in the synthesis of peptides with
      extremely difficult sequences.
AB  - N(alpha)-Protected alpha-amino acid bromides were easily generated in situ with 1
      bromo-N,N-2-trimethyl-1-propenylamine from the corresponding amino acids under
      very mild conditions. o-Nbs and the azido moieties proved to be compatible with
      these overactivated halides and were successfully applied in difficult peptide
      bond formations. N-Deprotection methods and the total step-by-step solution
      synthesis of a peptide containing up to seven consecutive L-(alphaMe)Valine
      residues are also reported. The assembly of this homopeptide was achieved in a
      short time and in very high yields by the azido/bromide system in a single
      repetitive operation.

PMID- 12201757
TI  - Aromatic allylation via diazotization: metal-free C-C bond formation.
AB  - A new method for the synthesis of allyl aromatic compounds not involving any
      metal-containing reagent or catalyst has been developed. Arylamines substituted
      with a large number of different substituents were converted via diazotizative
      deamination with tert-butyl nitrite in allyl bromide and acetonitrile to the
      corresponding allyl aromatic compounds. The allylation reaction was found to be
      suitable for larger scale synthesis due to short reaction times, a nonextractive
      workup, and robustness toward moisture, air, and type of solvent.

PMID- 12201758
TI  - Retro [2 + 2 + 2] ring opening in tricyclobutabenzene derivatives.
      Thermochemistry and reaction barriers. A theoretical hybrid density functional
      study.
AB  - The starting materials, transition states, and products of the concerted retro [2
      + 2 + 2] ring-opening reactions of several tricyclobutabenzene derivatives
      substituted by double-bonded substituents were calculated at the B3LYP/6-31G
      theoretical level. It was found that the geometries of the products
      (cyclododecatriyne derivatives) are governed by the electronegativity of the
      substituents and hyperconjugation effects. The transition-state geometries of all
      the derivatives are similar. It was found that the retro [2 + 2 + 2] ring-opening
      reactions are endothermic (ca. 30-85 kcal mol(-1), depending on the substituents)
      with high barriers, ranging between ca. 95 and 115 kcal mol(-1). It is predicted
      that the tricyclobutabenzene derivatives under study will be stable when prepared
      and that they can be made by [2 + 2 + 2] intramolecular ring closure of the
      respective cyclododecatriyne derivative, especially with the use of transition
      metals as mediators or catalysts.

PMID- 12201759
TI  - Conformational studies by dynamic NMR. 91. Conformational stereodynamics of
      tetraethylmethane and analogous C(CH2X)4 compounds.
AB  - Variable-temperature NMR studies of tetraethylmethane (1a), tetrapropylmethane
      (1b), tetrachloromethylmethane (1c), tetrabromomethylmethane (1d),
      tetracyclopropylmethylmethane (1e), and tetrabenzylmethane (1f) show a range of
      dynamic behavior. Separate signals for two types of conformation are observed for
      1a, 1c, and 1d at low temperatures, with more than 95% of the molecules in a time
      averaged D2d conformation, and the S4 conformation as the minor populated
      alternative. Compound 1e populates only S4-type conformations but equilibrates
      slowly between degenerate versions of these at low temperatures. Compounds 1b and
      1f show a temperature-dependent spectrum but the low-temperature limit spectrum
      could not be observed. Ab initio calculations agree well with experiment on the
      conformational equilibria and suggest in particular that compounds 1b and 1f
      behave similarly to compounds 1a and 1e, respectively. A crystal structure of
      compound 1f is reported.

PMID- 12201760
TI  - Cyclization of 1-(2-alkynylphenyl)-3,3-dialkyltriazenes: a convenient, high-yield
      synthesis of substituted cinnolines and isoindazoles.
AB  - A new route to isoindazoles and cinnolines through the cyclization of (2
      alkynylphenyl)triazenes under neutral conditions is presented. The products that
      result from heating the starting triazenes depend on both the type of alkyne
      ortho to the triazene functionality and the temperature used. Butadiyne moieties
      ortho to dialkyltriazenes yield bis-isoindazole dimers when heated to 150 degrees
      C in MeI. A requirement for cyclization in MeI is that the (2
      alkynylphenyl)triazene must contain a suitably electron-withdrawing substituent
      on the phenyl ring to deactivate the triazene toward methylation-induced
      decomposition to an iodoarene. Ethynyl moieties ortho to dialkyltriazenes yield
      both isoindazole dimers as well as 3-formylisoindazoles when subjected to the
      same conditions. Replacing MeI with 1,2-dichlorobenzene as solvent allows for the
      general cyclization of (2-ethynylphenyl)dialkyltriazenes. Heating to 170 degrees
      C results in a mixture of isoindazole and cinnoline products, whereas the
      cinnolines are produced exclusively in high yield at 200 degrees C.
      Alternatively, the isoindazoles can be obtained in good to excellent yield by
      stirring a 1,2-dichloroethane solution of the starting triazene with CuCl
      overnight at 50 degrees C.

PMID- 12201761
TI  - Demand-based thiolate anion generation under virtually neutral conditions:
      influence of steric and electronic factors on chemo- and regioselective cleavage
      of aryl alkyl ethers.
AB  - Thiolate anions have been generated in a "demand-based" fashion under virtually
      neutral conditions for chemoselective deprotection of aryl alkyl ethers. Solvents
      play the critical role in making the reaction effective and should have high
      values of epsilon (>30), molecular polarizabilities (>10), and DN (>27) and low
      values of AN (<14). However, it is the combined effect of all of these physical
      properties that make a particular solvent effective. The reaction rates of
      cleavage of various aryl alkyl ethers are dependent on the steric crowding around
      the O-alkyl carbon and follow the order propargyl approximately allyl
      approximately benzyl > methyl > ethyl. Electron-withdrawing substituents increase
      the rate of ether cleavage reaction. The influence of the steric and electronic
      factors have been successfully exploited for selective deprotection of aryl alkyl
      ethers during inter- and intramolecular competitions.

PMID- 12201762
TI  - Electrophilic fluorinating reagent mediated synthesis of fluorinated alpha-keto
      Ethers, benzil, and 6,6'-dialkoxy-2,2'-bipyridines.
AB  - Interactions of various fluorinated and nonfluorinated alcohols with trans
      stilbene in the presence of electrophilic reagents were studied. Under neat
      conditions, reactions of trans-stilbene (1) with fluorinated alcohols, R(f)OH
      (R(f) = CF3CH2-, CFH2CH2-, CF3CF2CH2-, CF2H(CF2)3CH2-, (CF3)2CH-, (CF3)3C- (2a-f)
      in the presence of an electrophilic reagent, 1-(chloromethyl)-4-fluoro-1,4
      diazoniabicyclo[2.2.2]octane bis(tetrafluoroborate) (Selectfluor) or N,N-difluoro
      2,2'-bipyridinium bis(tetrafluoroborate) (MEC-31), gave alpha-keto ethers (3a-f)
      and benzil (4) in good to moderate yields. alpha-Keto ether and benzil formation
      was very much dependent on the reaction time, the degree of fluorination of the
      alcohols, and whether a solvent such as CH3CN, DMF or DMA was utilized. In
      solution, alpha-keto ethers and benzil did not form. Interestingly, under neat
      conditions, nonfluorinated alcohols, ROH (R = CH3-, CH3CH2-, CH3CH2CH2-,
      CH3CH2CH2CH2-, CH3CH2CH2CH2CH2CH2-) (5g-k) did not react with trans-stilbene in
      the presence of MEC-31 but gave 6,6'-dialkoxy-2,2'-bipyridines (6g-k),
      regioselectively, in excellent isolated yields. On the other hand, fluorinated
      alcohols did not react with MEC-31. Reaction of MEC-31 with an excess of
      diethylene glycol (7) gave the bipyridine derivative (8) in 88% isolated yield.
      Reaction of 8 either with diethylaminosulfur trifluoride (DAST) or bis(2
      methoxyethyl)aminosulfur trifluoride (Deoxofluor) readily produced the
      corresponding difluoro derivative (9) in 85% isolated yield. All new compounds
      have been characterized by spectroscopic and elemental analysis.

PMID- 12201763
TI  - New cationic olefin cyclization-pinacol reactions. Ring-expanding cyclopentane
      annulations that directly install useful functionality in the cyclopentane ring.
AB  - Two new tandem cationic olefin cyclization-pinacol reactions that provide
      cyclopentane-fused cycloalkanone products are described. Treatment of cis-1-[2
      alkenyl-2-(triethylsiloxy)cycloalkyl]but-3-en-2-ol derivatives 21-24 with triflic
      anhydride at -78 degrees C affords cycloalkanones 31-34 in 54-90% yields with
      diastereoselectivities of typically >20:1. In this unusual transformation, the
      starting cycloalkanone is ring-expanded and fused to a 2-alkenylcyclopentane
      fragment. Reaction of cis-(2-siloxy-2-alkenylcycloalkyl)pyrrolidin-1-ylethanones
      15-17 with triflic anhydride and 2,6-di-tert-butyl-4-methylpyridine (DTBMP) at 
      20 to +65 degrees C followed by hydrolysis of the intermediate iminium salts 64
      with aqueous KHCO(3) affords cycloalkanediones 46-48 in moderate yield and high
      diastereoselectivity (>20:1). These are the first examples of ring-expanding
      cyclopentane annulations that directly introduce a carbon side chain or carbonyl
      functionality at the cyclopentane C2 position. The high diastereoselectivities
      observed in these reactions are believed to arise from reaction through highly
      organized cyclic transition states.

PMID- 12201764
TI  - The 3-(N-tert-butylcarboxamido)-1-propyl group as an attractive
      phosphate/thiophosphate protecting group for solid-phase oligodeoxyribonucleotide
      synthesis.
AB  - Among the various phosphate/thiophosphate protecting groups suitable for solid
      phase oligonucleotide synthesis, the 3-(N-tert-butylcarboxamido)-1-propyl group
      is one of the most convenient, as it can be readily removed, as needed, under
      thermolytic conditions at neutral pH. The deprotection reaction proceeds rapidly
      (t(1/2) approximately 100 s) through an intramolecular cyclodeesterification
      reaction involving the amide function and the release of the
      phosphate/thiophosphate group as a 2-(tert-butylimino)tetrahydrofuran salt.
      Incorporation of the 3-(N-tert-butylcarboxamido)-1-propyl group into the
      deoxyribonucleoside phosphoramidites 1a-d is achieved using inexpensive raw
      materials. The coupling efficiency of 1a-d in the solid-phase synthesis of
      d(ATCCGTAGCTAAGGTCATGC) and its phosphorothioate analogue is comparable to that
      of commercial 2-cyanoethyl deoxyribonucleoside phosphoramidites. These
      oligonucleotides were phosphate/thiophosphate-deprotected within 30 min upon
      heating at 90 degrees C in Phosphate-Buffered Saline (PBS buffer, pH 7.2). Since
      no detectable nucleobase modification or significant phosphorothioate
      desulfurization occurs, the 3-(N-tert-butylcarboxamido)-1-propyl group represents
      an attractive alternative to the 2-cyanoethyl group toward the large-scale
      preparation of therapeutic oligonucleotides.

PMID- 12201765
TI  - Synthesis of [1,3]dithiole and spiro[1,3]dithiole thiopyran derivatives of the
      [1,2]dithiolo[1,4]thiazine ring system.
AB  - We report the synthesis of some new polysulfur-nitrogen heterocycles by
      cycloaddition reactions to readily available tricyclic condensed 1,2-dithiole-3
      thiones. Thus, treatment of bis[1,2]dithiolopyrrole ketothione 1 with diacyl
      acetylenes gave the bis-aducts 2a-d. On the other hand, cycloaddition of
      bis[1,2]dithiolo[1,4]thiazine ketothione 3 with 1 equiv of acyl or diacyl
      acetylenes gave [1,3]dithiolylidenyl[1,2]dithiolo[1,4]thiazines 4a-f in fair to
      high yields. Catalysis by scandium triflate was used in the reactions that
      implied the less reactive dipolarophiles. Treatment of 3 with 2 equiv of DBA gave
      the bis-aduct 5a, and reaction of 4c with DMAD gave the mixed bis-adduct 5b.
      Cyclic voltammetry of selected examples showed irreversible processes that were
      influenced by the electrochemical activity of peripheral groups bonded to the
      heterocyclic system.

PMID- 12201767
TI  - Total synthesis of (+)-dihydrocuscohygrine and cuscohygrine.
AB  - The first enantioselective synthesis of (+)-dihydrocuscohygrine 1 and
      cuscohygrine 2 is presented. 1 was obtained in nine steps and 30% overall yield
      with a ruthenium-catalyzed tandem ring rearrangement metathesis key step starting
      from enantiomerically pure cycloheptene-1,3,5-triol derivative 6. The unknown
      absolute configuration of natural dihydrocuscohygrine 1 could be determined as
      (S,S)-(-). Cuscohygrine 2 was obtained by Jones oxidation of 1 in quantitative
      yield but unfortunately with complete epimerization.

PMID- 12201766
TI  - Subincanadines A-C, novel quaternary indole alkaloids from Aspidosperma
      subincanum.
AB  - Three novel quaternary indole alkaloids with an unprecedented 1
      azoniatricyclo[4.3.3.0(1,5)]undecane moiety, subincanadines A-C (1-3), as well as
      two new indole alkaloids with a 1-azabicyclo[5.2.2]undecane moiety,
      subincanadines D (4) and E (5), and a new indole alkaloid with a 1
      azabicyclo[4.3.1]decane moiety, subincanadine F (6), have been isolated from the
      barks of Aspidosperma subincanum Mart, and the structures of 1-6 and the
      stereochemistry of 1-3 were elucidated by spectroscopic data and chemical means.

PMID- 12201768
TI  - Thionation with the reagent combination of phosphorus pentasulfide and
      hexamethyldisiloxane.
AB  - The combination of P4S10 and hexamethyldisiloxane efficiently converts esters,
      lactones, amides, lactams, and ketones to their corresponding thiono derivatives.
      In the presence of elemental sulfur, 3-oxoesters are converted to dithiolethiones
      by this reagent. Yields are comparable to or superior to those obtained with
      Lawesson's reagent. The method has the advantage that reagent-derived byproducts
      may be removed by a simple hydrolytic workup or by filtration through silica gel,
      rather than by chromatography, as required for Lawesson's reagent.

PMID- 12201769
TI  - Synthesis of the cytotoxic sponge metabolite haliclamine A.
AB  - A new convergent and unified synthesis of the marine natural alkaloid haliclamine
      A is described. The synthesis of 3-alkylpyridine monomers 8 and 9 was first
      achieved from a common thiophene intermediate 5. These syntheses make use of
      thiophene chemistry and the ability of cyclopropylcarbinols 20 and 21 to
      rearrange to the homoallylic bromides 22 and 23, respectively. The Zincke
      procedure for the synthesis of pyridinium salts was then applied to the
      corresponding amino derivatives 8 and 9 to give efficiently unsymmetrical bis
      pyridinium macrocycle 1, whose reduction afforded haliclamine A.

PMID- 12201770
TI  - Aqueous hydroxide as a base for palladium-catalyzed amination of aryl chlorides
      and bromides.
AB  - The amination of aryl halides in the presence of inexpensive and air-stable
      alkali metal hydroxide bases and Pd[P(t-Bu)3]2 as catalyst gave arylamines in
      high yields. The reactions were conducted with a catalytic amount of
      cetyltrimethylammonium bromide as phase-transfer agent and either aqueous
      hydroxide or solid hydroxide in the presence of water. This combination of alkali
      metal hydroxide base, H2O, and the ammonium salt performed as well as NaO-t-Bu in
      the amination of p-chlorotoluene with dibutylamine. Hydroxide base was suitable
      for reactions of a wide range of aryl chlorides and bromides with aliphatic and
      aromatic amines. Some functional groups that were intolerant of tert-butoxide
      base, such as esters, enolizable ketones, nitriles, and nitro groups, were
      tolerated by the combination of hydroxide base, H2O, and cetyltrimethylammonium
      bromide in toluene solvent.

PMID- 12201771
TI  - Addition of organolithium reagents to corannulene and conformational preferences
      in 1-alkyl-1,2-dihydrocorannulenes.
AB  - Addition of organolithium reagents to corannulene (1) produces 1-R-1,2
      dihydrocorannulenes (2), which can be easily converted to 1-R-corannulenes (3).
      Molecular mechanics (MM) calculations predict a slight pseudoequatorial
      preference for the small substituents in both exo and endo arrangements of 2,
      whereas bulky substituents are expected to favor strongly the exo-pseudoaxial
      location. X-ray diffraction studies show the exo-pseudoaxial conformation in the
      solid state for both i-Pr and t-Bu-2. In solution, a gradual increase in the
      contribution of pseudoequatorial conformations with decreasing size of the
      substituent is demonstrated by analysis of the (3)J H-H coupling constants within
      the reduced ring.

PMID- 12201772
TI  - Intermolecular Diels-Alder reactions of brominated masked o-benzoquinones with
      electron-deficient dienophiles. A detour method to synthesize
      bicyclo[2.2.2]octenones from 2-methoxyphenols.
AB  - Intermolecular Diels-Alder reactions of masked o-benzoquinones, i.e., 6,6
      dimethoxy-2,4-cyclohexadienones 5-7 and 21-24 generated from 2-methoxyphenols 1-3
      and 17-20, respectively, with electron-deficient dienophiles leading to highly
      functionalized bicyclo[2.2.2]octenones are described. The masked o-benzoquinones
      (MOBs) 5-7 underwent Diels-Alder cycloadditions with methyl acrylate, methyl
      methacrylate, and methyl vinyl ketone to provide bicyclo[2.2.2]octenones 13a-c to
      15a-c (direct method) in low to moderate yields with the concomitant formation of
      considerable amounts of dimers 9-11. To retard dimerization and to improve the
      yields of the requisite bicyclo[2.2.2]octenones, a detour method comprised of
      sequential bromination of 2-methoxyphenols 1-4, oxidation and Diels-Alder
      reaction, and debromination has been developed. The oxidation of bromophenols 17
      20 produced MOBs 21-24 which are stable enough to be isolated. The MOBs 21-24
      underwent cycloaddition with electron-deficient dienophiles in a very efficient
      manner to afford the corresponding cycloadducts 25a-c to 28a-c in good to high
      yields without self-dimerization. When the cycloadducts 25a-c to 28a-c were
      treated with either Bu(3)SnH/AIBN or tributylammonium formate-palladium reagent,
      the corresponding debrominated products 13a-cto 16a-c were obtained in high to
      excellent yields. In general, the cycloadducts 13a-c to 15a-c were obtained in 20
      40% higher yields via the detour method than those via the direct method. In both
      routes, the Diels-Alder reactions proceeded in a highly regio- and
      stereoselective manner to furnish a single cycloadduct in each case.

PMID- 12201773
TI  - Facile synthesis of plasmalogens via Barbier-type reactions of vinyl dioxanes and
      vinyl dioxolanes with alkyl halides in LiDBB solution.
AB  - Plasmalogens (i.e. plasmenylcholines or plasmenylethanolamines) are a
      biologically important class of glycerophospholipids that have been difficult to
      synthesize due to the presence of an acid and oxidatively labile (Z)-vinyl ether
      substituent at the sn-1 position and a base-labile sn-2 acyl substituent that
      easily migrates during silica gel purification. We report two facile synthetic
      methods for the preparation of racemic plasmenylcholines via a tandem reductive
      vinyl dioxane/dioxolane ring opening and alkyliodide coupling process that
      proceeds in a single pot reaction. The key step in the formation of (Z)-vinyl
      ether precursors for the production of plasmenylcholines is accomplished using
      LiDBB under Barbier-type conditions to give the corresponding TBDMS-protected 1-O
      Z'-vinylglycerol intermediate in moderate yields. This pathway is the most direct
      synthetic route for the formation of plasmenylcholines to date, requiring a total
      of six transformations from acrolein and glycerol or solketal as inexpensive
      starting materials, to generate glycerophosphocholine-type plasmalogens in 4%
      overall yield.

PMID- 12201774
TI  - Synthesis of 2,4-methanoproline analogues via an addition-intramolecular
      substitution sequence.
AB  - A new two-step synthetic approach toward 3-(chloromethyl)cyclobutanone is
      described and used in the synthesis of 2,4-methanoproline analogues. The key step
      consists of a reversible addition of hydrogen cyanide onto the imines 12 in 50
      74% yield under conditions that allow ring closure. 2-Alkyl-2
      azabicyclo[2.1.1]hexane-1-carbonitriles 19, synthesized in four steps, can also
      be converted to the corresponding amines.

PMID- 12201775
TI  - Chromogenic indoaniline armed-calix[4]azacrowns.
AB  - Two novel chromogenic 1,3-alternate calix[4]azacrown (1) and calix[4]-bis
      azacrown (2) in which an indoaniline chromophore was attached on the nitrogen
      atom of the azacrown unit with one methylene spacer were synthesized. The 1H NMR
      spectrum of the ligand 1 and Ca2+ proved that the metal ion is entrapped by the
      calix[4]azacrown unit and by the conjugated indoaniline system. From the UV/vis
      band shifts upon metal ion complexation, Zn2+ ion was found to give the largest
      band shifts compared to other metal cations, indicating that Zn2+ ion (K(a) = 18
      760 M(-)(1) for 1 and K(a) = 19 930 M(-1) for 2) was selectively encapsulated by
      the calix[4]azacrown cavity with assistance of the pendent indoaniline sidearm.

PMID- 12201776
TI  - Synthesis and photophysical properties of light-harvesting arrays comprised of a
      porphyrin bearing multiple perylene-monoimide accessory pigments.
AB  - We present the synthesis and characterization of new light-harvesting arrays
      containing two, four, or eight perylene-monoimide accessory pigments attached to
      a zinc porphyrin. Each perylene is substituted with one or three 4-tert
      butylphenoxy substituents. A 4,3'- or 4,2'-diarylethyne linker joins the perylene
      N-imide position and the porphyrin meso-position, affording divergent or
      convergent architectures, respectively. The architectures are designed to provide
      high solubility in organic media and facile perylene-to-porphyrin energy
      transfer, while avoiding charge-transfer quenching of the excited porphyrin
      product. For the array containing four perylenes per porphyrin in both nonpolar
      (toluene) and polar (benzonitrile) media and for the array containing eight
      perylenes per porphyrin in toluene, the photoexcited perylene-monoimide dye (PMI)
      decays rapidly ( approximately 3.5 ps) and predominantly (>or=90%) by energy
      transfer to the zinc porphyrin to form the excited zinc porphyrin (Zn), which has
      excited-state characteristics (lifetime, fluorescence yield) comparable (within
      approximately 10%) to those of the isolated chromophore. For the array containing
      eight perylenes in benzonitrile, PMI decays approximately 80% by energy transfer
      (forming Zn) and approximately 20% by hole transfer (forming PMI- Zn+); Zn
      subsequently decays approximately 20% by electron transfer (also forming PMI-
      Zn+) and approximately 80% by the normal routes open to the porphyrin monomer
      (intersystem crossing, internal conversion, fluorescence). In addition to rapid
      and efficient perylene-to-porphyrin energy transfer, the broad blue-green to
      yellow absorption of the perylene dyes complements the blue absorption of the
      porphyrin, resulting in excellent light harvesting across a significant spectral
      region. Collectively, the work described herein identifies multiperylene
      porphyrin arrays that exhibit suitable photochemical properties for use as motifs
      in larger light-harvesting systems.

PMID- 12201777
TI  - Studies in bicyclo[3.1.0]hexane methanolysis. Ring opening of activated
      cyclopropanes under acidic and basic conditions.
AB  - A bicyclo[3.1.0]hexane, with one cyclopropane carbon flanked by a ketone and an
      ester or an aldehyde, undergoes methanolysis with cleavage of one of the two
      activated cyclopropane bonds, depending on the reaction conditions. Acidic
      conditions yield primarily or exclusively a 4-methoxycyclohexane, while basic
      conditions yield a 3-methoxymethylcyclopentanone.

PMID- 12201778
TI  - Absolute configuration of tert-butyl-1-(2-methylnaphthyl)phosphine oxide.
AB  - The enantiomers of tert-butyl-1-(2-methylnaphthyl)phosphine oxide 1 have been
      separated using a homemade HPLC column and an analytical gradient system.
      Vibrational absorption and circular dichroism spectra for both enantiomers have
      been measured in CD2Cl2 and CH2Cl2 solutions in the 2000-900 cm(-1) region. The
      fully relaxed potential energy surface of (S)-tert-butyl-1-(2
      methylnaphthyl)phosphine oxide, obtained using the B3LYP functional with a 6-31G
      basis set, indicated two stable conformers with their populations in a
      approximately 2:1 ratio. The vibrational absorption and VCD spectra are predicted
      for these two conformers using the B3LYP functional with a 6-31G basis set. The
      comparison of predicted and experimental spectra indicated that (+)-tert-butyl-1
      (2-methylnaphthyl)phosphine oxide is in the (S)-configuration. This assignment is
      supported by the ab initio prediction of positive optical rotation for the most
      stable conformer with an (S)-configuration and the nonequivalence sense of the
      tert-butyl group chemical shift observed in the 1H NMR spectrum of this
      enantiomer measured in the presence of (+)-(S)-mandelic acid as a chiral
      solvating agent.

PMID- 12201779
TI  - Practical and convenient enzymatic synthesis of enantiopure alpha-amino acids and
      amides.
AB  - Catalyzed by the nitrile hydratase and the amidease in Rhodococcus sp. AJ270
      cells under very mild conditions, a number of alpha-aryl- and alpha-alkyl
      substituted DL-glycine nitriles 1 rapidly underwent a highly enantioselective
      hydrolysis to afford D-(-)-alpha-amino acid amides 2 and L-(+)-alpha-amino acids
      3 in high yields with excellent enantiomeric excesses in most cases. The overall
      enantioselectivity of the biotransformations of nitriles originated from the
      combined effects of a high L-enantioselective amidase and a low enantioselective
      nitrile hydratase. The influence of the substrates on both reaction efficiency
      and enantioselectivity was also discussed in terms of steric and electronic
      effects. Coupled with chemical hydrolysis of D-(-)-alpha-phenylglycine amide,
      biotransformation of DL-phenylglycine nitrile was applied in practical scale to
      produce both D- and L-phenylglycines in high optical purity.

PMID- 12201781
TI  - Improved synthesis of 2,2'-bipyrimidine.
AB  - A high-yield synthesis was developed for the preparation of 2,2'-bipyrimidine (1)
      using the Ullmann coupling of 2-iodopyrimidine. The new procedure was also used
      for the preparation of 4,4',6,6'-tetramethyl-2,2'-bipyrimidine (2) and 5,5'
      dibromo-2,2'-bipyrimidine (3).

PMID- 12201780
TI  - Daphmanidin A, a novel hexacyclic alkaloid from Daphniphyllum teijsmanii.
AB  - A novel alkaloid with an unprecedented fused-hexacyclic skeleton, daphmanidin A
      (1), and a new pentacyclic alkaloid, daphmanidin B (2), have been isolated from
      the leaves of Daphniphyllum teijsmanii, and the structures were elucidated on the
      basis of spectroscopic data. The relative and absolute stereochemistry of 1 was
      determined by combination of NOESY correlations and a modified Mosher method.

PMID- 12201782
TI  - Novel reactivity of SeO2 with 1,3-dienes: selenophene formation.
AB  - A novel and efficient method for the synthesis of selenophenes is disclosed.
      Selenophenes were synthesized in high yields in a single operation from 1,3
      dienes containing a carbonyl group at the C-1 position and selenium dioxide. The
      bidirectional synthesis of selenophenes can also be demonstrated using this
      method. The selenophene is believed to form via a [4 + 2] cycloaddition between
      diene and selenium dioxide.

PMID- 12201783
TI  - Reagent for synthesis of secondary amines by two consecutive N-alkylations and
      its application to orthogonally protected spermidine.
AB  - A novel reagent, tert-butyl 2-naphthalenesulfonylcarbamate, has been designed to
      allow the stepwise synthesis of secondary aliphatic amines by two consecutive N
      alkylations with intermediate Boc-cleavage and final desulfonylation under mild
      and experimentally convenient conditions. Its application was demonstrated to
      make an orthogonally protected spermidine derivative, suitable for further
      selective modification. Each individual step, including the final cleavage of 2
      naphthalenesulfonyl to provide the secondary amine nitrogen, took place in high
      yield.

PMID- 12201784
TI  - Stereoselective synthesis of (+)-boronolide.
AB  - The delta-lactone boronolide (+)-1, a pharmacologically active, naturally
      occurring product, has been synthesized in enantiopure form with L-erythrulose as
      the chiral starting material. The key steps of the synthesis were a highly
      stereoselective aldol-reduction one-pot sequence, an indium-mediated
      diastereoselective aldehyde allylation, and a ring-closing metathesis.

PMID- 12201785
TI  - Versatile "traceless" sulfone linker for SPOS: preparation of isoxazolinopyrrole
      2-carboxylates.
AB  - A five-step solid-phase synthesis of isoxazolinopyrrole-2-carboxylates (6) that
      employs a traceless sulfone linker strategy is reported. Resin-bound diene 4,
      obtained by acetylation and concomitant beta-elimination of acetate from resin
      bound allylic alcohol 3, underwent regioselective 1,3-dipolar cycloadditons with
      nitrile oxides. Formation of the pyrrole products in a resin-releasing strategy
      was performed by pyrrole annulation with alkyl isocyanoacetates, which react with
      the vinyl sulfone moiety to generate the target isoxazolinopyrrole-2-carboxylates
      (6). Use of this chemistry afforded eight isoxazolinopyrrole-2-carboxylates in 6
      24% overall yields from polystyrene/divinylbenzene sulfinate 1.

PMID- 12201786
TI  - A two-step conversion of alpha,beta-unsaturated ketones to their alpha-carbalkoxy
      or alpha-carbamoyl derivatives.
AB  - Several enones are converted into their alpha-iodo derivatives in excellent
      yields and carbonylated with palladium catalysis in the presence of alcohol or
      amines to the alpha-carbonyl enones in satisfactory yields.

PMID- 12201787
TI  - Selective deoxygenation of leurosine: concise access to anhydrovinblastine.
AB  - Straightforward access to anhydrovinblastine starting from the parent alkaloid
      leurosine is reported. The key deoxygenation step was first optimized on a model
      substrate. However, applied to leurosine, only the low-valent Cp2TiCl gave
      satisfactory results.

PMID- 12201788
TI  - Steric hindrance-controlled Pd(0)-catalyzed coupling-cyclization of 2,3
      allenamides and organic iodides. An efficient synthesis of iminolactones and
      gamma-hydroxy-gamma-lactams.
AB  - Under the catalysis of 1 mol % Pd(PPh3)4, the reaction of 4,4-disubstituted 2,3
      allenamides and organic iodides in toluene afforded iminolactones
      stereospecifically in >90% yields using K2CO3 (2 equiv)-5 mol % TBAB as the base.
      A similar reaction with 4-monosubstituted 2,3-allenamides afforded gamma-hydroxy
      gamma-lactams in relatively lower yields. The N/O-attack selectivity may be
      determined by the steric effect at the 4-position of 2,3-allenamides.

PMID- 12201789
TI  - EPR support for the ketyl radical-anion "triggered" [3,3]-sigmatropic
      rearrangement.
AB  - New physical evidence to support a ketyl radical-anion mechanism for the [3,3]
      sigmatropic rearrangement is presented. With use of EPR spectroscopy, spectra are
      observed that can be attributed to 8, an acyl radical-anion species resulting
      from a [3,3]-rearrangement; this also functions as a key intermediate in the
      process. The spectrum of an additional paramagnetic species resulting from
      further addition of tin-centered radicals to the reaction product was also
      observed.

PMID- 12201790
TI  - A novel synthetic route to chiral gamma-lactams from alpha-amino acids via Rh
      catalyzed intramolecular C-H insertion.
AB  - Highly functionalized gamma-lactams are key intermediates for the synthesis of
      numerous biologically significant natural products. We herein described the
      synthesis of various chiral gamma-lactams via intramolecular C-H insertion of
      alpha-diazo-alpha-(phenylsulfonyl)acetamides derived from alpha-amino acids,
      which possess various functional groups. The cyclizations were highly regio- and
      stereoselective to afford chiral gamma-lactam motifs in high yields.

PMID- 12201791
TI  - Prospective study designs in outcomes research: the case of migraine.
AB  - Patient-reported outcomes (PROs), including resource utilisation, productivity
      and quality of life, are important outcomes in the field of migraine. Clinical
      trials have begun to incorporate PROs; however, not all research questions can be
      answered fully within the framework of a clinical trial design. Other prospective
      designs, including effectiveness trials, observational studies, and study hybrids
      may be used to answer many of the different research questions related to PROs.
      This paper reviews prospective study designs, their strengths and weaknesses, and
      examples of their application in migraine health-outcomes research. Guidance is
      provided for researchers in the selection of prospective research designs and the
      incorporation of PROs-research objectives.

PMID- 12201792
TI  - Cost effectiveness of implantable cardioverter defibrillator therapy versus drug
      therapy for patients at high risk of sudden cardiac death.
AB  - The implantable cardioverter defibrillator (ICD) is a therapy for patients at
      risk of sudden cardiac death due to ventricular tachycardia (VT) or ventricular
      fibrillation (VF). But the apparent high cost of ICD therapy relative to
      antiarrhythmic drugs such as amiodarone has raised questions about the cost
      effectiveness of ICD therapy versus drug therapy. To inform this debate we
      reviewed the literature on ICD cost effectiveness. An electronic and manual
      search was conducted for articles published since 1980 reporting original data on
      the cost effectiveness of ICD versus drug therapy for patients at risk of VT/VF.
      Data on costs and life-years gained were abstracted and studies were grouped into
      those that used decision-analysis models and those that were trial-based
      analyses. Cost-effectiveness ratios were inflated to 2001 US dollars. Nine
      studies were included in the review; five studies were modelling studies and four
      were part of randomised trials of ICD therapy. Studies varied in time horizon,
      but all except one indicated that ICD therapy was more costly than drug therapy.
      Early decision models assumed larger survival benefits than those observed in
      subsequent trials and therefore had attractive incremental cost-effectiveness
      ratios in the range of dollars US 27000 to dollars US 60000 per life-year gained.
      Trial-based studies, with the exception of one small trial, indicated cost per
      life-year gained in the range dollars US 44000 to dollars US 144000. Stratified
      analysis shows clearly that patients with a greater risk of mortality due to
      structural heart disease (e.g. left ventricular ejection fraction < or =35%)
      benefit more from ICD therapy and therefore have a more attractive cost
      effectiveness ratio than patients at lower risk. ICD therapy is still evolving
      over time with implant costs declining and device technology improving. Current
      evidence is that, in selected patients who are at high risk of VT/VF, ICD therapy
      can be a cost-effective option. Future research should focus on (i) patient
      selection to optimise benefits for available resources; and (ii) more
      comprehensive outcome measures to include health-related quality of life.

PMID- 12201793
TI  - Valuation of symptomatic hepatitis a in adults: estimates based on time trade-off
      and willingness-to-pay measurement.
AB  - BACKGROUND: The cost effectiveness of hepatitis A prevention is typically
      assessed by comparing vaccination costs with the number of life-years saved. This
      endpoint does not consider the benefits of preventing nonfatal yet symptomatic
      infections. Nearly as many days of healthy life are lost to hepatitis A morbidity
      as mortality. OBJECTIVE: To investigate the value American adults place on
      preventing hepatitis A symptoms by using the willingness-to-pay and time trade
      off metrics. METHODS: We provided a written description of hepatitis A symptoms
      to 181 American adults, who judged the amounts of money and lifespan they would
      forego to avoid them. The description made no reference to the possibility of
      fatality, and respondents were asked not to consider costs of medical care and
      work loss. We investigated relationships between demographic characteristics and
      each metric, the relationship between the two metrics, and the test/re-test
      reliability of the metrics. RESULTS: Respondents would pay a median of dollars US
      2000 (inter-quartile range, dollars US 500 to 5000; 2001 values) for risk-free
      prevention of hepatitis A symptoms. Alternatively, they would forego a median of
      28 days survival (inter-quartile range, 6 to 40 days) for cost-free prevention.
      There was modest correlation between willingness-to-pay and time trade-off
      responses (r = 0.24, p < 0.01), suggesting these metrics measure independent
      aspects of preference. Strong correlations between measures obtained 30 days
      apart support the test/re-test reliability of willingness to pay (r = 0.70, p <
      0.01) and time trade-off (r = 0.73, p < 0.01) metrics. In multivariate analyses,
      higher household income (p = 0.02) predicted greater willingness to pay in
      dollars. Male gender (p < 0.01) predicted greater willingness to forego life
      expectancy for better health. CONCLUSION: In our study population of US adults,
      most were willing to pay or trade life expectancy for a hypothetical preventative
      drug for hepatitis A symptoms. The amount respondents were willing to pay appears
      dependent on their income level while males are willing to trade more life
      expectancy than female respondents. The values expressed should be considered in
      assessments of hepatitis A prevention.

PMID- 12201794
TI  - Burden of illness in irritable bowel syndrome comparing Rome I and Rome II
      criteria.
AB  - OBJECTIVES: To evaluate the burden of illness in irritable bowel syndrome (IBS),
      in terms of resource utilisation (direct and indirect) and health-related quality
      of life (HR-QOL), in individuals with IBS who meet Rome I and Rome II criteria.
      METHODS: A cross-sectional study, carried out by personal interview, on a
      representative sample (n = 2000) of the Spanish population. Individuals with
      suspected IBS were identified via a screening question and subsequently given an
      epidemiological questionnaire to complete. The questionnaire collected
      information on IBS symptoms, resource utilisation, and HR-QOL [Medical Outcomes
      Study 36-item Short Form (SF-36)]. RESULTS: Sixty-five individuals met Rome II
      criteria for IBS, while 146 individuals met exclusively Rome I criteria. Of Rome
      II individuals, 67.7% had consulted some type of healthcare professional in the
      previous 12 months, compared with only 41.8% of those individuals meeting
      exclusively Rome I criteria (p vs 17.1%); 'drug consumption' (70.8 vs 45.2%); and
      'reduced performance in main activity' (60 vs 27.4%). Compared with the general
      population, the study sample reported significantly worse HR-QOL scores in four
      dimensions of the SF-36 ('bodily pain', 'vitality', 'social functioning' and
      'role-emotional'. Additionally, individuals meeting Rome II criteria reported
      worse HR-QOL scores than those individuals meeting exclusively Rome I criteria,
      especially in the 'bodily pain' and 'general health' dimensions. CONCLUSIONS: The
      burden of illness in IBS is important and correlated to the diagnostic criteria
      employed. Individuals who met Rome II criteria reported a higher level of
      resource utilisation and worse HR-QOL than individuals meeting exclusively Rome I
      criteria.

PMID- 12201795
TI  - Cost-utility analysis of primary prophylaxis versus treatment on-demand for
      individuals with severe haemophilia.
AB  - OBJECTIVE: To assess the cost effectiveness of primary prophylaxis with clotting
      factor instead of treatment following a bleed (on-demand) for individuals with
      severe haemophilia. DESIGN: Different data sources on the clinical effects and
      costs of treatments were combined using a Markov model. SETTING: English
      treatment centres. PERSPECTIVE: UK societal. PARTICIPANTS: Hypothetical cohorts
      of 100 individuals with severe haemophilia A or B or severe von Willebrands
      disease. INTERVENTIONS: Primary prophylaxis treatment on-demand with clotting
      factor. OUTCOME MEASURES: Costs, quality-adjusted life-years (QALYs) and
      incremental cost per QALY in UK pounds ( pound, 1999/2000 values). RESULTS: The
      baseline results showed that treating individuals with severe haemophilia
      A/severe von Willebrands disease or severe haemophilia B with primary prophylaxis
      instead of treatment on-demand cost an additional pound 46500 and pound 8600 per
      QALY gained, respectively. However, the results were extremely sensitive to a
      number of factors including the clotting factor unit cost, the time between
      prophylactic doses and the discount rate. CONCLUSIONS: Despite the high costs of
      treatment, primary prophylaxis was cost effective compared with treatment on
      demand in some scenarios. Primary prophylaxis is more likely to be cost effective
      for individuals with severe haemophilia B compared with individuals with severe
      haemophilia A/severe von Willebrands disease. Further research is required to
      assess the relationship between methods of clotting factor infusion and health
      related quality-of-life.

PMID- 12201796
TI  - Conjoint analysis of a new Chemotherapy: willingness to pay and preference for
      the features of raltitrexed versus standard therapy in advanced Colorectal
      Cancer.
AB  - OBJECTIVE: To estimate the willingness to pay for a new chemotherapy, raltitrexed
      (Tomudex trade mark ) over conventional therapy with fluorouracil plus leucovorin
      (FU-LV) from the perspective of patients with advanced colorectal cancer. The
      study was part of the product's reimbursement application in Australia. DESIGN
      AND METHODS: The key differences relevant to patients between the two therapies,
      frequency of administration and severity of mouth ulceration, were used to
      develop a self-administered questionnaire. A relatively new technique to
      healthcare, that of conjoint analysis (CA), was used to estimate willingness to
      pay and strength of preference. A discrete choice CA was used. Analysis was via a
      logit model with adjustment for the cluster effect (or intra-patient
      correlation). STUDY PARTICIPANTS: Oncology nurses served as proxies for patients
      with advanced colorectal cancer. RESULTS: The participation rate was 87% (62/71)
      with questionnaires from 56 respondents eligible for analysis. The CA method
      generated a mean incremental willingness to pay of 745 Australian dollars (dollar
      A; dollars US 507) per cycle of chemotherapy, comprising dollars A 550 (dollars
      US 374) and dollars A 195 (dollars US 133) for the toxicity and administration
      improvements, respectively (1998 values). Both features were related to
      preference with independent odds of 6.87 and 1.98, respectively, however only the
      toxicity attribute was a significantly related to preference. Subscription to
      private health insurance was the only significant demographic predictor
      identified, however, the homogeneous income structure of the respondents seems
      likely to have masked any significant income effect. CONCLUSIONS: This study
      highlights the advantages of using CA in healthcare, where new therapies or
      treatments are often composed of a number of attributes. The CA allows both
      strength of preference and willingness to pay for individual treatment attributes
      to be estimated and can be used to assign statistical significance to these
      parameters.

PMID- 12201797
TI  - The impact of health economics on healthcare delivery: a health economist's
      perspective: a primary care response.

PMID- 12201798
TI  - Cost effectiveness of asthma management strategies.

PMID- 12201800
TI  - Balance confidence among people with lower-limb amputations.
AB  - BACKGROUND AND PURPOSE: Confidence in a person's balance has been shown to be an
      important predictor of social activity among people with lower-limb amputations.
      The purposes of this study were to describe confidence in balance among people
      with transtibial or transfemoral lower-limb amputations and to compare people
      whose amputations were due to vascular and nonvascular causes. SUBJECTS AND
      METHODS: A survey of a sample of 435 community-dwelling individuals from 2
      regional clinics was conducted. The sample consisted of people with unilateral
      transfemoral (26.7%) and transtibial (73.3%) amputations who lost their limb for
      vascular (53%) and nonvascular (47%) reasons. The mean age of the primarily male
      (71%) sample was 62.0 years (SD=15.7). RESULTS: Mean scores, using the Activities
      specific Balance Confidence (ABC) Scale, were 63.8 for the total sample, 54.1 for
      the subjects with amputations due to vascular reasons, and 74.7 for the subjects
      with amputations due to nonvascular reasons. Given a maximum possible ABC Scale
      score of 100, the results suggest that confidence was low. A difference between
      the subjects with amputations due to vascular reasons and those with amputations
      due to nonvascular reasons was observed over each item of the ABC Scale.
      Variables that were statistically related to balance confidence included age,
      sex, etiology, mobility device use, the need to concentrate while walking,
      limitations in activities of daily living, depression, and fear of falling.
      DISCUSSION AND CONCLUSION: Balance confidence scores among the study sample were
      low when compared with values previously reported by other researchers.
      Confidence was particularly low among individuals who had their amputation for
      vascular reasons. Balance confidence might be an important area of clinical
      concern.

PMID- 12201801
TI  - Determinants of the sit-to-stand movement: a review.
AB  - BACKGROUND AND PURPOSE: The sit-to-stand (STS) movement is a skill that helps
      determine the functional level of a person. Assessment of the STS movement has
      been done using quantitative and semiquantitative techniques. The purposes of
      this study were to identify the determinants of the STS movement and to describe
      their influence on the performance of the STS movement. METHODS: A search was
      made using MEDLINE (1980-2001) and the Science Citation Index Expanded of the
      Institute for Scientific Information (1988-2001) using the key words "chair,"
      "mobility," "rising," "sit-to-stand," and "standing." Relevant references such as
      textbooks, presentations, and reports also were included. Of the 160 identified
      studies, only those in which the determinants of STS movement performance were
      examined using an experimental setup (n=39) were included in this review.
      RESULTS: The literature indicates that chair seat height, use of armrests, and
      foot position have a major influence on the ability to do an STS movement. Using
      a higher chair seat resulted in lower moments at knee level (up to 60%) and hip
      level (up to 50%); lowering the chair seat increased the need for momentum
      generation or repositioning of the feet to lower the needed moments. Using the
      armrests lowered the moments needed at the hip by 50%, probably without
      influencing the range of motion of the joints. Repositioning of feet influenced
      the strategy of the STS movement, enabling lower maximum mean extension moments
      at the hip (148.8 N m versus 32.7 N m when the foot position changed from
      anterior to posterior). DISCUSSION AND CONCLUSION: The ability to do an STS
      movement, according to the research reviewed, is strongly influenced by the
      height of the chair seat, use of armrests, and foot position. More study of the
      interaction among the different determinants is needed. Failing to account for
      these variables may lead to erroneous measurements of changes in STS performance.

PMID- 12201802
TI  - The effect of prolonged static and cyclic stretching on ankle joint stiffness,
      torque relaxation, and gait in people with stroke.
AB  - BACKGROUND AND PURPOSE: Continuous passive motion (cyclic stretching applied to
      the subject's limb) has been used for the rehabilitation of some orthopedic
      impairments; however, few researchers have considered its application in the
      management of neurological disorders such as stroke. The purpose of this study
      was to examine the short-term effects of prolonged static and cyclic calf
      stretching on passive ankle joint stiffness, torque relaxation, and gait in
      people with ischemic stroke. SUBJECTS: Ten community-dwelling people (mean
      age=64.6 years, SD=8.76, range=53-76) who were diagnosed with a cerebrovascular
      accident volunteered to be subjects. METHODS: Participants engaged in one 30
      minute static stretch and one 30-minute cyclic stretch of the calf muscle, using
      an isokinetic dynamometer that also collected torque and angle measurements.
      Before and after treatments, 10-m walking times were collected. Ankle joint
      stiffness was calculated from the slope of the torque and angle curves before and
      immediately after treatments, and torque relaxation was calculated as the
      percentage of decrease in peak passive torque over the 30-minute stretch
      durations. RESULTS: Ankle joint stiffness decreased by 35% and 30% after the
      static and cyclic stretches, respectively. Stiffness values and 10-m walk times
      were not different between conditions. The amount of torque relaxation was 53%
      greater for static stretching than for cyclic stretching. DISCUSSION AND
      CONCLUSION: These preliminary data from a very small sample of people with stroke
      indicate that ankle joint stiffness decreases after both prolonged static and
      cyclic stretches; however, neither technique appears to be better at reducing
      stiffness in people with stroke. Torque relaxation is greater after static
      stretching than after cyclic stretching, and walking speed does not appear to be
      influenced by the stretching treatments used in our study.

PMID- 12201803
TI  - Dual task interference during gait in people with Parkinson disease: effects of
      motor versus cognitive secondary tasks.
AB  - BACKGROUND AND PURPOSE: Exacerbation of movement disorders while doing 2 tasks
      (dual task performance) is a characteristic feature of Parkinson disease (PD).
      The aim of this investigation was to identify whether the type of secondary task
      (motor or cognitive) determined the severity of dual task interference. SUBJECTS
      AND METHODS: Footstep patterns for 15 people with PD and 15 comparison subjects
      without PD were compared when they walked: (1) at a self-selected speed, (2)
      while simultaneously performing a motor task (coin transference), and (3) while
      simultaneously performing a cognitive task (digit subtraction). Gait speed,
      stride length, cadence, and the percentage of the gait cycle in double-limb
      stance (DS) were examined with a computerized stride analyzer. RESULTS: When
      there was no second task, the mean stride length was less in the group with PD
      (1.29 m) than in the comparison group (1.51 m), and the mean gait speed was less
      in the group with PD (71.47 m/min) than in the comparison group (87.29 m/min).
      The mean cadence was less in the group with PD (110.79 steps/min) than in the
      comparison group (115.81 steps/min). The percentage of the gait cycle in DS was
      greater in the group with PD (33.38%) than in the comparison group (31.21%). Both
      groups reduced their stride length and speed when they had to change from unitask
      performance to dual task performance and DS increased. For the group with PD,
      cadence also decreased. For both groups, the type of secondary task had a
      negligible effect on the performance decrement. DISCUSSION AND CONCLUSION:
      Although the performance of simultaneous motor or cognitive tasks compromised
      gait in people with PD, the type of secondary task was not a major determinant of
      the severity of dual task interference.

PMID- 12201804
TI  - Virtual reality-augmented rehabilitation for patients following stroke.
AB  - BACKGROUND AND PURPOSE: Recent evidence indicates that intensive massed practice
      may be necessary to modify neural organization and effect recovery of motor
      skills in patients following stroke. Virtual reality (VR) technology has the
      capability of creating an interactive, motivating environment in which practice
      intensity and feedback can be manipulated to create individualized treatments to
      retrain movement. CASE DESCRIPTION: Three patients (ML, LE, and DK), who were in
      the chronic phase following stroke, participated in a 2-week training program (3
      1/2 hours a day) including dexterity tasks on real objects and VR exercises. The
      VR simulations were targeted for range of motion, movement speed, fractionation,
      and force production. OUTCOMES: ML's function was the most impaired at the
      beginning of the intervention, but showed improvement in the thumb and fingers in
      range of motion and speed of movement. LE improved in fractionation and range of
      motion of his thumb and fingers. DK made the greatest gains, showing improvement
      in range of motion and strength of the thumb, velocity of the thumb and fingers,
      and fractionation. Two of the 3 patients improved on the Jebsen Test of Hand
      Function. DISCUSSION: The outcomes suggest that VR may be useful to augment
      rehabilitation of the upper limb in patients in the chronic phase following
      stroke.

PMID- 12201805
TI  - Role of stress peptides during human pregnancy and labour.
AB  - Premature birth is the major source of perinatal death and disability.
      Furthermore, the intrauterine health of the baby is important for preventing
      certain adult diseases. However, the molecular mechanisms driving the onset of
      human labour remain uncertain, although several key players have been identified.
      It is becoming clear that there are many pathways to parturition in humans.
      Stress peptides, in particular placental corticotrophin releasing hormone (CRH)
      and possibly the related peptide urocortin, appear to play important roles
      throughout pregnancy. Plasma CRH is a predictor of the duration of human
      gestation. During most of pregnancy, CRH, acting via specific CRH receptor
      subtypes, plays a 'protective' role by promoting myometrial quiescence via the
      generation of cAMP and cGMP, and upregulation of nitric oxide synthase
      expression. At term, myometrial contractility is enhanced by a complex series of
      molecular switches, involving the upregulation of oxytocin receptor expression
      and crosstalk between the oxytocin and CRH receptors. This results in protein
      kinase C-induced phosphorylation of specific CRH receptor subtypes, with
      subsequent desensitization and a shift in the intracellular microenvironment to
      enhance contractility. CRH/urocortin, via specific receptor isoforms, is now able
      to activate Gq and potentially enhance the oxytocin-driven generation of inositol
      triphosphate. In addition, CRH/urocortin, via specific CRH receptor subtypes, may
      generate prostaglandins from the fetal membranes and decidua, play a role in
      placental vasodilatation and participate in fetal adrenal function and organ
      maturation. These peptides and receptors are phylogenetically ancient and well
      preserved across species. They may have evolved as a mechanism to protect against
      the 'stress' of premature birth.

PMID- 12201806
TI  - Oestrogen's masculine side: mediation of mating in male mice.
AB  - This review focuses on the role of oestrogen in male sexual behaviour using
      oestrogen receptor alpha and beta knockout (ERalphaKO and ERbetaKO) mouse models.
      ERbetaKO mice are capable of mating and producing offspring, whereas ERalphaKO
      mice are unable to do either. When ERalphaKO males are treated with testosterone
      or dihydrotestosterone (DHT), < 50% display mounting behaviour, few intromit and
      none ejaculate. However, concurrent treatment with testosterone and a dopamine
      agonist instates masculine sexual behaviour in both male and female ERalphaKO
      mice. Dopamine content in the preoptic area and associated regions is not
      affected by oestrogen receptor alpha gene disruption. However, expression of
      neuronal nitric oxide synthase immunoreactivity is severely reduced in ERalphaKO
      males compared with wild-type males. These findings, together with studies
      conducted in aromatase knockout mice, are at odds with the dogma that oestrogen
      is required during development for expression of male sexual behaviour in adults.
      However, they do support a role for oestrogens, mediated by oestrogen receptor
      alpha, in regulation and production of neuronal nitric oxide synthase, which in
      turn may control dopamine agonist release. As has been shown in male rats, in
      mice dopamine agonist release is likely to be an essential component of the
      neural pathway that mediates male sexual behaviour.

PMID- 12201807
TI  - Spermatogenesis and steroidogenesis in mouse, hamster and monkey testicular
      tissue after cryopreservation and heterotopic grafting to castrated hosts.
AB  - Retrieval, extracorporal storage and autotransplantation of testicular tissue
      could become an important strategy for preserving male gonadal function. The
      present study used syngeneic and immunodeficient nude mice as hosts, and immature
      and adult mice, neonatal and adult photoregressed Djungarian hamsters and
      neonatal marmosets to identify the potential of testicular tissue grafting to
      maintain the morphological and functional integrity of the testis. Testicular
      tissue was grafted s.c. either as fresh tissue or after cryopreservation into
      adult, orchidectomized hosts. The mice that received rodent testis tissue were
      autopsied 50 days later, and blood samples were collected. Sixty-five per cent of
      mouse isografts contained morphologically normal testicular tissue and
      seminiferous tubules with some degree of spermatogenic recovery. Mature
      spermatozoa were recovered after enzymatic disaggregation. Although the recovery
      of spermatogenesis was limited in adult mouse and hamster tissue, complete
      spermatogenesis was observed in grafts from immature rodents. Testicular tissue
      from neonatal marmosets developed up to the stage of spermatocytes at day 135
      after xenografting. Androgen concentrations were comparable in intact control
      mice and in mice receiving fresh mouse and hamster grafts, slightly lower in mice
      receiving cryopreserved grafts and adult photoregressed hamster tissue, and low
      in castrated control mice and in mice receiving marmoset tissue. These results
      show that isografts and xenografts of immature and adult testicular tissue become
      functionally active as a s.c. graft in the mouse and that this approach might be
      useful in combination with cryopreservation as a tool for storage and activation
      of the male germ line and androgen replacement therapy in patients.

PMID- 12201808
TI  - Role of matrix metalloproteinase 2 in the ovulatory folliculo-luteal transition
      of ewes.
AB  - Tissue dissolution and remodelling are associated with the processes of rupture
      of the ovulatory follicle and formation of the corpus luteum. Matrix
      metalloproteinase 2 (MMP-2) belongs to a family of endopeptidases that cleave
      extracellular proteins; its primary substrate is the lattice network of basement
      membranes that support epithelial cells and endothelium. The aim of this study
      was to ascertain a putative regulatory role of MMP-2 relevant to the folliculo
      luteal transformation in ewes. Luteal regression and the preovulatory surge of
      gonadotrophins were synchronized by administration of PGF(2alpha) and GnRH on
      days 14.0 and 15.5 of the oestrous cycle, respectively. Dominant antral follicles
      present during pro-oestrus consistently ovulate approximately 24 h after GnRH
      administration. Normal IgG or a bioactivity-neutralizing MMP-2 monoclonal
      antibody was injected into the antral cavity of preovulatory follicles at 8 h
      after GnRH administration. Jugular blood samples were obtained for serum
      progesterone analysis and ovaries were removed for light microscopic morphometry
      on day 8. A definitive ovulation stigma was evident in control ewes. The antra of
      ruptured follicles had largely been supplanted with luteal tissue. In contrast,
      the ovarian surface contiguous with follicles injected with anti-MMP-2 was smooth
      and undisturbed, which is indicative of a failure of ovulation. Luteinized
      unruptured follicles were filled with (entrapped) fluid. Corpora lutea of control
      animals contained numerous connective tissue projections that provided a
      framework for cellular migration and angiogenesis. Luteal tissues that surrounded
      the cavity of antibody-treated follicles lacked trabeculae and were deficient in
      blood vessels. Systemic venous progesterone concentrations were lower in ewes
      with a luteinized unruptured follicle compared with those with a corpus luteum.
      It is proposed that MMP-2 is a mediator of ovulation and luteal development.

PMID- 12201809
TI  - Caspase activity and expression of cell death genes during development of human
      preimplantation embryos.
AB  - It has been observed that apoptosis occurs in human blastocysts. In other types
      of cell, the characteristic morphological changes seen in apoptotic cells are
      executed by caspases, which are regulated by the BCL-2 family of proteins. This
      study investigated whether these components of the apoptotic cascade are present
      throughout human preimplantation development. Developing and arrested two
      pronucleate embryos at all stages were incubated with a fluorescently tagged
      caspase inhibitor that binds only to active caspases, fixed, counterstained with
      4,6-diamidino-2-phenylindole (DAPI) to assess nuclear morphology and examined
      using confocal microscopy. Active caspases were detected only after compaction,
      at the morula and blastocyst stages, and were frequently associated with
      apoptotic nuclei. Occasional labelling was seen in arrested embryos. Expression
      of proapoptotic BAX and BAD and anti-apoptotic BCL-2 was examined in single
      embryos using RT-PCR and immunohistochemistry. BAX and BCL-2 mRNAs were expressed
      throughout development, whereas BAD mRNA was expressed mainly after compaction.
      Simultaneous expression of BAX and BCL-2 proteins within individual embryos was
      confirmed using immunohistochemistry. The onset of caspase activity and BAD
      expression after compaction correlates with the previously reported appearance of
      apoptotic nuclei. As in other types of cell, human embryos express common
      molecular components of the apoptotic cascade, although apoptosis appears to be
      suppressed before compaction and differentiation.

PMID- 12201810
TI  - Effects of oocyte maturation regimen on the relative abundance of gene
      transcripts in bovine blastocysts derived in vitro or in vivo.
AB  - Bovine embryos produced in vitro differ substantially from embryos produced in
      vivo in the mRNA expression patterns of genes important for development. Several
      factors in the in vitro production systems have profound effects on embryonic
      mRNA expression patterns. The effects of the type of maturation on the expression
      pattern of genes important for development in blastocysts produced in vitro have
      not yet been investigated. The aim of the present study was to investigate the
      effects of various maturational protocols on the relative abundance of a panel of
      six marker genes, indicative of compaction and cavitation, metabolism, stress
      susceptibility and RNA processing, in bovine blastocysts produced in vitro. Four
      groups of blastocysts were analysed by a sensitive semi-quantitative RT-PCR
      assay. Blastocysts were produced in vitro from oocytes of different origin from:
      (1) 3-8 mm follicles; (2) preovulatory follicles before the LH surge; and (3)
      preovulatory follicles 24 h after the LH surge. The first two groups were matured
      in vitro, whereas the third group had undergone maturation in vivo. A fourth
      group comprised blastocysts developed entirely in vivo. Expression of glucose
      transporter 1 was significantly (P < 0.05) higher, and expression of desmocollin
      2 and plakophilin tended to be higher (P < 0.1) for in vivo (group 4) compared
      with in vitro blastocysts (group 1), whereas no differences were found for heat
      shock protein 70.1, E-cadherin and poly(A) polymerase. Expression of the six
      transcripts did not differ among blastocysts produced in vitro from oocytes of
      groups 1, 2 and 3. Results indicate that alterations in the relative abundance of
      these transcripts in blastocysts produced in vitro cannot primarily be attributed
      to the origin of the oocyte, but are likely to have been induced by post
      maturation or fertilization culture conditions.

PMID- 12201811
TI  - An extreme bias in the germ line of XY C57BL/6<->XY FVB/N chimaeric mice.
AB  - Chimaeric analysis is a powerful method to address questions about the cell
      autonomous nature of defects in spermatogenesis. Symplastic spermatids (sys) mice
      have a recessive mutation that causes male sterility due to an arrest in germ
      cell development during spermiogenesis. Chimaeric mice were generated by
      aggregation of eight-cell embryos from sys (FVB/N genetic background) and wild
      type C57BL/6 (B6) mice to determine whether the male germ-cell defect is cell
      autonomous. The resulting FVB/N<->B6 chimaeras (<-> denotes fusion of embryos)
      were mated with FVB/N mice and coat colour of offspring was used to identify
      transmission of FVB/N or B6 gametes. Regardless of the relative contribution of
      B6 to somatic tissues of the chimaeras, almost all (282 of 284; 99.3%) offspring
      of B6 XY<->XY FVB/N (+/+ or sys/+) males (n = 9) received a FVB/N-derived
      paternal gamete. After mating of female B6<->FVB/N chimaeras, 51 of 73 (69.9%)
      offspring received an FVB-derived maternal gamete. Southern blot analysis of
      different tissues from chimaeric males indicated that, despite the presence of
      balanced chimaerism in somatic tissues, the germ line in B6 XY<->XY FVB/N mice
      was essentially FVB/N in composition. Thus there is a strong selective advantage
      for FVB/N male germ cells over B6 male germ cells in B6<->FVB/N-aggregation
      chimaeras at some stage during development of the male germ line. Each of three
      male chimaeras that were either B6 XY<->XY FVB/N (sys/sys) or B6 XX<->XY FVB/N
      (sys/sys) in composition was sterile, and testis histology was essentially
      sysmutant. This finding indicates that the function of the gene(s) affected in
      the sys mutation may be required in the testis, although whether expression is
      required in germ cells, somatic cells or both remains unknown. The extreme bias
      in transmission of male gametes has implications for experimental design in
      studies that use chimaeric analysis to address questions regarding the cell
      autonomous nature of germ-cell defects in mice.

PMID- 12201812
TI  - The gamma-subunit of the Na-K-ATPase as a potential regulator of apical and
      basolateral Na+-pump isozymes during development of bovine pre-attachment
      embryos.
AB  - Expression and activity of the Na-K-ATPase within the basolateral membrane
      domains of the trophectoderm epithelium provide the driving force for
      accumulation of Na(+) and Cl(-) across the nascent epithelium, mediating fluid
      movement into the forming blastocoel. Within the trophectoderm of the bovine
      blastocyst, multiple isozymes of the Na-K-ATPase are expressed.
      Immunolocalization has demonstrated that the alpha1-isozyme localizes within the
      basolateral membrane, whereas the alpha 3-isozyme localizes to the apical cell
      margins. Gene-specific RT-PCR and wholemount indirect immunofluorescence confocal
      laser scanning microscopy were used to examine expression of the Na-K-ATPase
      gamma-subunit (a regulatory subunit of the Na-K-ATPase) throughout development of
      bovine preattachment embryos in vitro. Expression of mRNA transcripts for the
      gamma-subunit was detected throughout bovine pre-attachment development from the
      fertilized one-cell embryo to the blastocyst stage. A similar pattern of
      expression was also observed for gamma-subunit protein, and immunofluorescence
      was detected within the membranes of embryonic blastomeres at all stages of
      development. In contrast to the expression patterns observed for the alpha
      subunits, gamma-subunit proteins were detected in both the basolateral and apical
      cell margins of the trophectoderm, and surrounding all cells of the inner cell
      mass. Co-localization studies demonstrated that gamma-subunit peptides are co
      expressed with the alpha1-subunit in the basolateral domains of the
      trophectoderm. These results indicate a role for the gamma-subunit of the Na-K
      ATPase in modulating Na(+)-pump activity in both apical and basolateral margins
      of the trophectoderm during formation and expansion of the bovine blastocyst, and
      adds a further level of complexity to Na(+)-pump regulation of cavitation.

PMID- 12201813
TI  - Quantification of mast cells and microflora in the vaginal cul-de-sac of the
      brushtail possum (Trichosurus vulpecula).
AB  - Mast cells are typically associated with biological responses to intracellular
      parasitic or bacterial invasion in gut and pulmonary tissues. Large numbers of
      these cells are present in the vaginal cul-de-sac, a component of the
      reproductive tract in female brushtail possums (Trichosurus vulpecula). The
      presence of mast cells in this area may reflect microbial presence or indicate a
      role for mast cells in reproductive function in this marsupial. In this study,
      the number and spatial location of mast cells in vaginal cul-de-sac tissues at
      different reproductive stages was determined, and related to the presence of
      microflora. Vaginal cul-de-sac tissue was collected from juvenile (n = 5),
      lactationally anoestrous and cyclic adult brushtail possums (n = 6 per group).
      Oestrous cyclicity was induced by removal of pouch young and reproductive status
      was confirmed by laparoscopy. Tissue was collected aseptically for
      microbiological procedures. The fractionator and optical disector stereological
      methods were used to quantify mast cell populations. In all groups, microflora
      populations were low (< 5 x 10(5) organisms g(-1)). Mast cell density in
      epithelial tissue was highest in lactationally anoestrous and luteal phase
      brushtail possums and lowest in follicular phase animals. No correlation between
      the numbers of bacteria isolated and mast cell density was apparent. Gram stained
      tissue showed no evidence of bacterial invasion. Mast cell density was
      significantly lower in epithelial tissue from follicular phase animals,
      corroborating previous studies in which an increase in mast cell degranulation
      coincided with high oestrogen concentrations.

PMID- 12201814
TI  - Interleukin 8 in the cervix of non-pregnant ewes.
AB  - Studies of cervical artificial insemination of ewes at hormone-synchronized
      oestrus indicate that the cervix remains relatively impenetrable to semen, in
      contrast to naturally breeding animals. During parturition the inflammatory
      response plays an important part in cervical dilation and possibly, to a lesser
      extent, in the non-pregnant cervix at oestrus to facilitate the transcervical
      transport of semen. The expression of interleukin 8 (IL-8), a pro-inflammatory
      cytokine in the ovine cervix, has been mapped and quantified, using semi
      quantitative in situ hybridization, to ascertain the role played by inflammation
      in the ovine cervix during natural and artificially induced oestrous cycles. IL-8
      gene expression was observed in both the luminal epithelium and fibroblastic
      cells of the cervix. The presence of IL-8 was confirmed using
      immunohistochemistry. IL-8 gene expression in the luminal epithelium varied
      throughout the oestrous cycle and was highest at oestrus and at day 5 of the
      oestrous cycle. In ewes artificially induced to ovulate, either by the withdrawal
      of progesterone pessaries after treatment for 12 days, or by two i.m. injections
      of prostaglandin 9 days apart, IL-8 gene expression at oestrus was significantly
      lower than it was at natural oestrus. Insemination increased IL-8 gene expression
      in progesterone-synchronized ewes. These data support the hypothesis that IL-8
      induced inflammation is important in normal cervical function and that this
      process is inhibited during artificial synchronization of the oestrous cycle and
      is increased by exposure to semen.

PMID- 12201815
TI  - Localization of transforming growth factor beta2 (TGFbeta2) and its receptors,
      TbetaRI and TbetaRII, in uteri and blastocysts of the stripe-faced dunnart
      (Sminthopsis macroura) during gastrulation.
AB  - This study describes for the first time the spatial and temporal distribution of
      a growth factor and its receptors in uteri and conceptuses of a marsupial species
      during the peri-gastrulation period. Uteri (gravid and non-gravid) and
      blastocysts from 40 female stripe-faced dunnarts (Sminthopsis macroura) were
      collected over the peri-gastrula period (days 6.0-8.5) and stained
      immunohistochemically for transforming growth factor beta2 (TGFbeta2) and its
      receptors, TbetaRI and TbetaRII, to determine possible roles for TGFbeta2 in
      marsupial embryonic development. The events that occurred during the period
      examined included the appearance and proliferation of hypoblast and mesoderm,
      primitive streak and node formation, and early neurulation. Differences in
      TGFbeta2 quantities between gravid and non-gravid uteri reflect differences in
      uterine morphology, indicating a role for TGFbeta2 in endometrial remodelling. In
      blastocysts, large quantities of all three proteins in the trophectoderm during
      the node stage coincide with both blastocyst expansion before implantation and
      the appearance of multinucleated cells, indicating that TGFbeta2 plays a role in
      conceptus elongation and trophectoderm differentiation. In contrast, lack of
      TbetaRII in blastocysts during hypoblast formation and proliferation negates any
      role for TGFbeta2 in these processes, as both receptors are required for a
      response to TGFbeta2. High concentrations of TGFbeta2 but low concentrations of
      TbetaRII in blastocysts during early primitive streak formation indicate that
      paracrinal embryo-maternal signalling may be occurring, as blastocysts cannot
      respond to TGFbeta2 at this stage, but uteri could. A similar situation, but
      reversed, also occurs during primitive node formation.

PMID- 12201816
TI  - Expression of prolactin-related protein I at the fetomaternal interface during
      the implantation period in cows.
AB  - The bovine placenta secretes multiple molecules during implantation and
      placentation, many of which are produced by binucleate cells. In this study,
      production of prolactin-related protein I (PRP-I), a member of the non-classical
      prolactin-related family, was investigated during the implantation period in
      cows. Expression of bovine PRP-I (bPRP-I) in the placentome was examined during
      the preimplantation (days 17-19), implantation (days 20-25) and post-implantation
      (days 30-60) periods by immunohistochemistry, immunofluorescence and in situ
      hybridization. During the preimplantation period, both bPRP-I and bovine
      placental lactogen (bPL) were undetectable in trophoblastic cells. Both bPRP-I
      mRNA and protein appeared first at day 20 of gestation in trophoblastic
      binucleate cells and multinuclear cells that might migrate into the endometrium
      and fuse to epithelium; however, no bPL was detected in binucleate cells at this
      time. After implantation, on day 30, both bPRP-I and bPL were detected in
      binucleate cells and were co-expressed in the same cells. These data indicate
      that bPRP-I may play a role before implantation and that bPRP-I may be an
      excellent marker for trophoblastic cell differentiation, as well as a candidate
      for pregnancy diagnosis.

PMID- 12201817
TI  - Changes in insulin-like growth factor binding protein (IGFBP) isoforms during
      bovine follicular development.
AB  - UThe insulin-like growth factor binding proteins (IGFBPs) bind IGFs with high
      affinity and so regulate their access to the type 1 and 2 IGF receptors. This is
      the principal mechanism involved in regulating IGF bioavailability during
      folliculogenesis. IGFBPs undergo a number of post-translational modifications,
      including proteolytic cleavage, phosphorylation and glycosylation, which can
      regulate the affinity of IGFBPs for IGFs. However, the post-translational changes
      to IGFBPs that occur during folliculogenesis have not been fully characterized.
      The charge and size variants of the IGFBPs in bovine follicular fluid were
      examined by two-dimensional non-reducing SDS-PAGE followed by non-isotopic
      western ligand blot analysis, and immunoblot analysis during follicular
      development. The results demonstrate the presence of at least 51 IGFBP isoforms
      corresponding to IGFBP-1 to -6 in bovine follicular fluid from subordinate
      follicles, many of which were phosphorylated. The total number of IGFBPs was
      reduced in dominant follicles, whereas no gross changes in isoforms were observed
      during follicular development. These results demonstrate the high degree of
      conservation of IGFBP post-translational modifications between species, and from
      the in vitro dephosphorylation of these proteins it is hypothesized that these
      modifications may result in changes to IGF binding or susceptibility to
      proteolytic cleavage.

PMID- 12201818
TI  - The first biantennary bacterial secondary cell wall polymer and its influence on
      S-layer glycoprotein assembly.
AB  - The cell surface of Aneurinibacillus thermoaerophilus DSM 10155 is covered with a
      square surface (S)-layer glycoprotein lattice. This S-layer glycoprotein, which
      was extracted with aqueous buffers after a freeze-thaw cycle of the bacterial
      cells, is the only completely water-soluble S-layer glycoprotein to be reported
      to date. The purified S-layer glycoprotein preparation had an overall
      carbohydrate content of 19%. Detailed chemical investigations indicated that the
      S-layer O-glycans of previously established structure accounted for 13% of total
      glycosylation. The remainder could be attributed to a peptidoglycan-associated
      secondary cell wall polymer. Structure analysis was performed using purified
      secondary cell wall polymer-peptidoglycan complexes. NMR spectroscopy revealed
      the first biantennary secondary cell wall polymer from the domain Bacteria, with
      the structure alpha-L-Glc p NAc-(1-->3)-beta-L-Man p NAc-(1-->4)-beta-L-Gal p NAc
      (1-->3)-alpha-L-Glc p NAc-(1-->3)-beta-L-Man p NAc-(1-->4)-beta-L-Gal p NAc-(1-
      >3)-alpha-L-Glc p NAc-(1-->4)-[alpha-L-Glc p NAc-(1-->3)-beta-L-Man p NAc-(1-->4)
      beta-L-Gal p NAc-(1-->3)-alpha-L-Glc p NAc-(1-->3)-beta-L-Man p NAc-(1-->4)-beta
      L-Gal p NAc-(1-->3)-alpha-L-Glc p NAc-(1-->3)]-beta-L-Man p NAc-(1-->3)-alpha-L
      Glc p NAc-(1-->3)-beta-L-Man p NAc-(1-->3)-alpha-L-Glc p NAc-(1-->3)-alpha-L-Glc
      p NAc-(1-->O)-PO(2)(-)-O-PO(2)(-)-(O-->6)-MurNAc- (where MurNAc is N 
      acetylmuramic acid). The neutral polysaccharide is linked via a pyrophosphate
      bond to the C-6 atom of every fourth N -acetylmuramic acid residue, in average,
      of the A1gamma-type peptidoglycan. In vivo, the biantennary polymer anchored the
      S-layer glycoprotein very effectively to the cell wall, probably due to the
      doubling of motifs for a proposed lectin-like binding between the polymer and the
      N-terminus of the S-layer protein. When the cellular support was removed during S
      layer glycoprotein isolation, the co-purified polymer mediated the solubility of
      the S-layer glycoprotein in vitro. Initial crystallization experiments performed
      with the soluble S-layer glycoprotein revealed that the assembly property could
      be restored upon dissociation of the polymer by the addition of poly(ethylene
      glycols). The formed two-dimensional crystalline S-layer self-assembly products
      exhibited the same lattice symmetry as observed on intact bacterial cells.

PMID- 12201819
TI  - Cloning and molecular expression analysis of large and small lecithin:retinol
      acyltransferase mRNAs in the liver and other tissues of adult rats.
AB  - Retinyl ester, the most abundant form of vitamin A (retinol), is synthesized by
      the enzyme lecithin:retinol acyltransferase (LRAT). Previously, we cloned a 2.5
      kb LRAT cDNA from rodent liver which codes for functional LRAT activity. However,
      Northern blots of tissues probed with the 2.5 kb cDNA revealed the presence of a
      larger transcript of approximately 5 kb as well as several smaller transcripts.
      To elucidate the nature of the large LRAT transcript, a high-molecular-mass
      adrenal gland cDNA library was screened. Two similar clones of 3962 and 3187 nt
      were identified which appeared to be part of the 3'-untranslated region (UTR) of
      a 5358 nt LRAT mRNA. The 5.3 kb cDNA was then amplified from liver by reverse
      transcriptase PCR (RT-PCR) and demonstrated to encode functional LRAT activity.
      The 3'-UTR of the 5.3 kb cDNA contains several AAUAAA polyadenylation signals.
      Analysis of the 3' ends of LRAT mRNA transcripts from liver, intestine and testis
      showed the usage of both canonical and non-canonical polyadenylation signals. To
      further analyse the LRAT mRNAs expressed in vivo, Northern blot analysis was
      performed using four probes spanning sections from the 5' end to the distal 3'
      end of the 5.3 kb LRAT cDNA. The results show that the major 5.3 kb transcript
      uses the canonical signal AAUAAA located at nt 5308, and the major short
      transcript of approximately 1.5 kb uses the non-canonical signal AUUAAA located
      at nt 1330. The 5.3 kb LRAT transcript was predominant in the liver of retinoic
      acid-repleted vitamin A-deficient rats, coincident with increased quantitative
      expression of LRAT mRNA and enzyme activity. The differential usage of these
      polyadenylation signals can explain the presence of multiple LRAT mRNA
      transcripts which are expressed in different tissue-specific patterns.

PMID- 12201820
TI  - Cathepsin B carboxydipeptidase specificity analysis using internally quenched
      fluorescent peptides.
AB  - We have examined in detail the specificity of the subsites S1, S2, S1' and S2'
      for the carboxydipeptidase activity of cathepsin B by synthesizing and assaying
      four series of internally quenched fluorescent peptides based on the sequence Dnp
      GFRFW-OH, where Dnp (2,4-dinitrophenyl) is the quenching group of the
      fluorescence of the tryptophan residue. Each position, except the glycine, was
      substituted with 15 different naturally occurring amino acids. Based on the
      results we obtained, we also synthesized efficient and sensitive substrates that
      contained o -aminobenzoic acid and 3-Dnp-(2,3-diaminopropionic acid), or epsilon
      amino-Dnp-Lys, as the fluorescence donor-receptor pair. The higher kinetic
      parameter values for the carboxydipeptidase compared with the endopeptidase
      activity of cathepsin B allowed an accurate analysis of its specificity. The
      subsite S1 accepted preferentially basic amino acids for hydrolysis; however,
      substrates with phenylalanine and aliphatic side-chain-containing amino acids at
      P1 had lower K m values. Despite the presence of Glu245 at S2, this subsite
      presented clear preference for aromatic amino acid residues, and the substrate
      with a lysine residue at P2 was hydrolysed better than that containing an
      arginine residue. S1' is essentially a hydrophobic subsite, and S2' has
      particular preference for phenylalanine or tryptophan residues.

PMID- 12201821
TI  - Genetics of type 2 diabetes and insulin resistance: knowledge from human studies.
AB  - Both type 2 diabetes mellitus (T2DM) and insulin resistance are complex traits in
      which multiple gene effects and metabolic and environmental factors combine to
      contribute to the overall pathogenesis of these conditions. This complexity has
      complicated the search for susceptibility genes and has led to different but
      complementary approaches being used for the detection of gene effects. These
      include the study of monogenic cases of insulin resistance and T2DM, association
      studies of candidate genes and genome-wide scans. The peroxisome proliferator
      activated receptor gamma (PPARgamma) and calpain-10 (CAPN10) genes have recently
      been identified as T2DM susceptibility genes, and the lessons learnt from these
      studies are helping to shape future strategies to search for additional
      susceptibility genes in T2DM and insulin resistance.

PMID- 12201822
TI  - Gonadal damage from 131I therapy for thyroid cancer.

PMID- 12201823
TI  - Biochemical markers of growth hormone (GH) sensitivity in children with
      idiopathic short stature: individual capacity of IGF-I generation after high-dose
      GH treatment determines the growth response to GH.
AB  - OBJECTIVE AND PATIENTS: To assess multiple dose-response relationships between
      three GH doses (1.5, 3.0 and 6.0 IU/m2) and nine different biochemical markers of
      GH sensitivity in a well-defined group of 17 children with idiopathic short
      stature (ISS). DESIGN AND MEASUREMENTS: Serum levels of IGF-I, IGF-II and IGFBP
      3, and peripheral markers leptin, C-terminal propeptide of type I collagen (PICP)
      and N-terminal propeptide of type III collagen (PIIINP), alkaline phosphatase
      (AP) and osteocalcin (OC) were measured at the start and after 2 and 12 weeks of
      periods of no treatment, GH 1.5 IU/m2 and GH 3.0 IU/m2. Twelve-week washout
      periods were applied between the 12-week GH-treatment periods. High-dose GH
      treatment was given during the second year of study and all serum markers were
      measured at start, after 2 and 12 weeks and 1 year of GH 6.0 IU/m2. In 18 non-GH
      treated children with ISS the same parameters were measured yearly. The bone
      resorption marker urinary deoxypyridinoline (DPD) was measured during 12-h day
      and night periods at start and after 2 weeks GH 1.5, 3.0 and 6.0 IU/m2. RESULTS:
      All markers were GH dependent, but the timing of maximal response varied among
      different markers. Height SDS at start, age at start and IGF-II at baseline were
      inversely related to the first-year growth response (r = -0.73, P = 0.001; r = 
      0.53, P = 0.03; and r = -0.53, P = 0.03, respectively). Some statistically
      significant correlations between biochemical responses on low GH doses (1.5 or
      3.0 IU/m2) and second-year growth response were found, but these showed no
      consistent pattern. However, all changes in IGF-I SDS after GH 6.0 IU/m2 measured
      either after 2 or 12 weeks or 1 year correlated significantly with the second
      year growth response (r = 0.55, P = 0.02; r = 0.81, P = 0.001; and r = 0.86, P <
      0.001, respectively). Baseline or GH-stimulated levels of peripheral markers did
      not correlate with the growth response. CONCLUSION: The individual capacity of
      IGF-I generation after high-dose GH treatment (6.0 IU/m2) determines the growth
      response on high-dose GH treatment. Peripheral markers do not seem to play a role
      in growth prediction of children with ISS.

PMID- 12201824
TI  - Screening for macroprolactinaemia and pituitary imaging studies.
AB  - OBJECTIVE: Hyperprolactinaemia is caused by high levels of monomeric, dimeric or
      macro forms of prolactin in circulation, the monomeric form being predominant in
      patients with prolactinomas. Macroprolactinaemia, however, is common and is
      associated with asymptomatic cases. In this study, we reviewed our records
      regarding clinical and imaging investigations in patients who were found to have
      hyperprolactinaemia predominantly due to the presence of macroprolactin and
      compared them with the findings observed in patients whose prolactin molecular
      size consisted predominantly of the monomeric form. PATIENTS AND METHODS: We
      conducted a retrospective study of 113 consecutive patients (nine men and 104
      women, aged 19-67 years, median age 39 years) with hyperprolactinaemia who were
      screened for the presence of macroprolactin by polyethylene glycol precipitation
      and/or chromatography and submitted to pituitary magnetic resonance imaging (MRI)
      and/or computerized tomography (CT). RESULTS: Fifty-two of 113 patients (46%) had
      hyperprolactinaemia due to macroprolactin, whereas the remaining 61 patients
      (54%) had their hyperprolactinaemia confirmed by the predominance of the
      monomeric form. Both groups shared similar mean prolactin levels (79.9 +/- 63.6
      micro g/l, median of 62.0 micro g/l, and 97.9 +/- 155.4 micro g/l, median of 61.0
      micro g/l, respectively). Of the patients with macroprolactinaemia, 46% had no
      symptoms of hyperprolactinaemia, whereas only 10% of the patients who screened
      negative for macroprolactin were asymptomatic. There was an association between
      macroprolactinaemia and negative pituitary imaging findings: normal pituitary
      images were found in 78.9% of patients who had macroprolactinaemia and in 25% of
      patients with monomeric hyperprolactinaemia. In addition, none of the patients
      with macroprolactinoma (seven cases) had macroprolactinaemia. CONCLUSIONS: The
      presence of macroprolactinaemia does not exclude the possibility of a pituitary
      adenoma and consequently may not prevent pituitary imaging studies. However, our
      data demonstrate that all asymptomatic patients who screened positive for
      macroprolactin had normal pituitary imaging studies. Patient samples showing
      hyperprolactinaemia should be first tested for macroprolactin, before the patient
      is submitted to imaging studies. We suggest that imaging studies should be
      ordered in patients with macroprolactinaemia when indicated by clinically
      relevant features. As a result, unnecessary anxiety and costly medical procedures
      may be prevented.

PMID- 12201825
TI  - The metabolic effects of short-term administration of physiological versus high
      doses of GH therapy in GH deficient adults.
AB  - OBJECTIVE: GH treatment has demonstrated favourable effects on most features of
      GH deficiency in hypopituitary adults. However, most studies employed
      supraphysiological GH doses, resulting in deterioration in insulin sensitivity
      (SI). The short-term metabolic effects of physiological doses of GH therapy in GH
      deficient (GHD) adults are largely unknown. We therefore compared the effects of
      short-term administration of two 'physiological' ('lowest' dose: 0.0017
      mg/kg/day; 'low' dose: 0.0033 mg/kg/day) with two 'supraphy-siological' ('high'
      dose: 0.010 mg/kg/day; 'highest' dose: 0.025 mg/kg/day) GH doses on SI, beta-cell
      function, IGF-1 and IGFBPs -1 and -3 in a group of GHD adults. PATIENTS AND
      METHODS: Thirteen GHD adults were recruited (seven men, aged 23-63 years). For
      each of the four doses, six patients (three men) were allocated randomly to
      undergo a 7-day treatment phase. Fasting blood samples were collected daily (days
      1-8), and SI and beta-cell function were calculated using the homeostasis model
      assessment (HOMA). RESULTS: All four GH doses increased IGF-1, IGFBP-3 and IGF
      1/IGFBP-3 ratio, and decreased IGFBP-1 from day 3 onwards (P < 0.05). The highest
      dose increased fasting glucose (P < 0.001), insulin (P < 0.001) and beta-cell
      function (P < 0.001), but decreased SI (P < 0.001). The high and low doses did
      not modify fasting glucose and insulin, SI or beta-cell function, whereas the
      lowest dose enhanced beta-cell function (P < 0.05). The overall increase in the
      GH dose increased IGF-1, IGFBP-3, fasting glucose and insulin (P < 0.001),
      demonstrated a positive correlation with the final change in fasting glucose (r =
      0.5, P < 0.05) and insulin (r = 0.8, P < 0.001) and a negative correlation with
      final SI (r = -0.5, P < 0.05). CONCLUSIONS: Our results suggest that short-term
      administration of the highest GH dose induced insulin resistance, whereas the
      lowest dose (0.0017 mg/kg/day) could represent the optimal starting dose in GHD
      adults due to its beneficial effects on beta-cell function without compromising
      SI. It is, however, yet to be determined whether the positive effects of the
      lowest GH dose on beta-cell function can be demonstrated over a longer period of
      time.

PMID- 12201826
TI  - Clinical manifestations and insulin resistance (IR) in polycystic ovary syndrome
      (PCOS) among South Asians and Caucasians: is there a difference?
AB  - OBJECTIVE: Polycystic ovary syndrome (PCOS) is more prevalent in South Asian
      women residing in the UK than in Caucasians. Insulin resistance (IR) is central
      to the pathogenesis of PCOS, while type 2 diabetes is commoner in South Asians.
      We aimed to determine a possible ethnic difference in the clinical and
      biochemical characteristics of South Asian vs. Caucasian women with PCOS.
      PATIENTS AND DESIGN: A case-control cross-sectional observational study of
      consecutive women with anovular PCOS (47 South Asians, 40 Caucasians) and their
      age-matched controls (11 South Asians and 22 Caucasians). MEASUREMENTS: Index
      subjects: a questionnaire-based interview on clinical symptoms and family
      history; anthropometric measurements, clinical observations of the presence and
      degree of acne, hirsutism and acanthosis nigricans; transvaginal pelvic
      ultrasound; biochemical analyses of fasting blood sugar, fasting plasma insulin,
      fasting lipids, testosterone, and SHBG concentrations. CONTROL GROUP: age- and
      weight-matched unrelated women from the same ethnic backgrounds without PCOS
      seeking treatment for male infertility were studied by similar methods to those
      used with the index subjects. RESULTS: South Asians with PCOS presented at a
      younger age (age 26 +/- 4 vs. 30.1 +/- 5 years, P = 0.005). Body mass index (BMI)
      and waist : hip ratios were similar in the two affected cohorts. More South
      Asians had oligomenorrhoea commencing at a younger age. Hirsutism (Ferriman
      Gallwey score 18 vs. 7.5, P = 0.0001), acne, acanthosis nigricans and secondary
      infertility were significantly more prevalent in South Asians. The fasting
      glucose was similar (4.52 +/- 0.08 vs. 4.62 +/- 0.09 mmol/l, P = 0.25), the
      fasting insulin higher (89.4 +/- 8.9 vs. 48.6 +/- 4.8 pmol/l, P = 0.0001) and
      insulin sensitivity (IS) lower (0.335 +/- 0.005 vs. 0.357 +/- 0.002, P = 0.0001)
      among South Asians. Serum SHBG was significantly less in South Asians (35 +/- 3.3
      vs. 55 +/- 9.4 nmol/l, P = 0.02), while serum testosterone was similar (2.69 +/-
      0.11 vs. 2.64 +/- 0.13 nmol/l, P = 0.37). CONCLUSIONS: We conclude that South
      Asians with anovular PCOS seek treatment at a younger age, have more severe
      symptoms, and have higher fasting insulin concentrations and lower insulin
      sensitivity than Caucasians.

PMID- 12201827
TI  - Contrasting effects of intrauterine growth retardation and premature delivery on
      adult cortisol secretion and metabolism in man.
AB  - OBJECTIVE: Among babies born at term, intrauterine growth retardation (IUGR)
      predicts adult hypertension and hyperglycaemia. This might be due to elevated
      circulating glucocorticoids in adulthood, as described in animal models and in
      several cohorts of men who were low birthweight at term. Recently, we found that
      premature low birthweight babies also have adult cardiovascular risk factors,
      irrespective of IUGR. We have now investigated cortisol secretion in this group.
      DESIGN PATIENTS AND MEASUREMENTS: We studied 29 women and 23 men aged 22-25 years
      who had been recruited at birth as either normal term (mean birthweight 3.1 kg,
      gestation 39 weeks), premature appropriate for gestational age (AGA; 1.7 kg, 32
      weeks), or premature IUGR (1.7 kg, 35 weeks) babies. Body composition was
      measured by dual-energy X-ray absorptiometry (DEXA); plasma was obtained at 0900
      h after overnight fast; and cortisol metabolites were measured in a 24-h urine
      sample by gas chromatography/mass spectrometry (GCMS). RESULTS: Cortisol
      metabolites were different in men and women, so results were analysed separately.
      Among women, adult body composition did not differ between groups. Plasma
      cortisol was not different, but total urinary cortisol metabolite excretion was
      lower in AGA (3.29 +/- 1.91 mg/day, n = 7, P < 0.02) than in either normals (6.77
      +/- 4.10, n = 14) or IUGR (9.47 +/- 8.84, n = 8). Relative excretion of cortisol
      and cortisone metabolites was not different. Statistically significant
      differences in cortisol parameters between groups were not seen in men.
      CONCLUSIONS: Premature AGA baby girls have lower cortisol secretion in adulthood
      but normal plasma cortisol, suggesting impaired metabolic clearance of cortisol.
      By contrast, premature IUGR babies maintain normal cortisol secretion as adults,
      suggesting that IUGR, rather than premature delivery, is responsible for
      programmed activation of the hypothalamic-pituitary-adrenal (HPA) axis. The
      ability to detect such dramatic differences in a small study suggests that
      programming has a potent influence on adult cortisol secretion.

PMID- 12201828
TI  - Spontaneous growth hormone secretory characteristics in children with partial
      growth hormone insensitivity.
AB  - OBJECTIVE: To investigate the characteristics of spontaneous GH secretion in four
      male children with short stature due to partial GH insensitivity. Their molecular
      defect consists of inclusion of a mutant intronic pseudoexon in the region of the
      GH receptor involved in homodimerization. SUBJECTS: The subjects were two pairs
      of brothers who were first cousins, aged 10.4-14.2 years, heights -3.3 to -5.6
      SDS, from a consanguineous Pakistani family. Basal serum IGF-I levels were
      extremely low (20-29 mg/l; NR > 50), with absent or minimal response to human
      recombinant GH (hGH) stimulation. Serum IGFBP-3 SDS levels were also low (-2.9 to
      -8.9). GH binding protein (GHBP) levels were normal (28.1-51.7%). METHODS:
      Spontaneous GH secretion was studied by intermittent (20 min) venous sampling
      from 2000 to 0800 h. The secretion profiles were analysed using the Pulsar
      programme and compared to data from a reference population of 76 prepubertal
      Swedish children [median age 10.7 years, median height -1.1 SDS (-2.0 to 1.4)]
      according to Swedish growth standards. RESULTS: Median (range) Pulsar-derived
      values in the four patients and controls were, respectively: GHmax (mU/l) 276.6
      (178.7-325.8) and 27.2 (13.1-94.9), mean GH (mU/l) 64.5 (41.9-77.8) and 5.8 (3.2
      20.6), baseline (mU/l) 12.3 (11.7-20.1) and 1.1 (0.2-6.1), AUCb (mU/l x 24 h)
      1210 (684-1555) and 112.5 (60.6-316.4), i.e. all parameters of GH secretion in
      the four patients were markedly elevated compared with the control population.
      CONCLUSIONS: Spontaneous GH secretion is elevated in partial GH insensitivity.
      This investigation could be of diagnostic value in children with short stature.

PMID- 12201829
TI  - The effect of long-term untreated growth hormone deficiency (GHD) and 9 years of
      GH replacement on the quality of life (QoL) of GH-deficient adults.
AB  - BACKGROUND: Quality of life (QoL) is reduced in GH-deficient adults compared with
      the normal population. Further support for the role of GH in the maintenance of
      QoL is derived from short-term studies of GH replacement in severely GH-deficient
      adults; these have predominantly reported beneficial effects, although the degree
      of improvement has often been modest. To date, however, there are few data to
      demonstrate whether this beneficial effect on QoL is maintained in the long term.
      PATIENTS AND METHODS: This study consisted of the follow-up of 85 GH-deficient
      adults who completed the Nottingham Health Profile (NHP) and the Psychological
      General Well-Being Schedule (PGWB) self-rating questionnaires in 1992, as part of
      a 12-month double-blind randomized study of GH replacement. In 2001 we attempted
      to contact all 85 patients and asked them to complete the two questionnaires
      again. Follow-up data were obtained in 61 patients. The findings were analysed
      according to whether the individual had received GH continuously since completion
      of the initial study, received no further GH replacement, or received GH
      replacement for only part of the intervening time. Both the NHP and the PGWB give
      a total score and subsection scores for six specific areas of QoL. A high score
      correlates with increased morbidity in the NHP, and with reduced morbidity in the
      PGWB. RESULTS: Fifty-nine patients completed the NHP at both time points. The
      patients who continued GH (n = 17) had significantly greater morbidity at
      baseline than patients who opted to discontinue therapy (n = 27), as reflected by
      the higher scores overall (5.7 +/- 4.0 vs. 2.8 +/- 3.5; P = 0.01) and in the
      energy subsection (47.0 +/- 34.7 vs. 13.2 +/- 28.6; P < 0.001). Over the study
      period energy levels improved in the patients who remained on GH therapy (47.0 +/
      34.7 vs. 25.7 +/- 31.0; P = 0.04). By contrast, a deterioration in the physical
      mobility subsection (2.4 +/- 5.4 vs. 8.2 +/- 16.7; P = 0.04) occurred in the
      patients who did not continue GH therapy, and no change occurred in the energy
      subsection. In the 36 patients who completed the PGWB significant differences
      were observed at baseline between patients who received GH replacement
      continuously (n = 10) and those who discontinued therapy (n = 21) in the overall
      score (67.2 +/- 14.1 vs. 86.8 +/- 14.7; P = 0.001); and in the subsections for
      anxiety (P = 0.04), depression (P = 0.04), well-being (P = 0.001), self-control
      (P = 0.04) and vitality (P < 0.001); the greater morbidity at baseline being
      observed in the patients who continued GH replacement. In the patients receiving
      GH continuously for 9 years the vitality subsection score improved significantly
      (7.7 +/- 2.4 vs. 12.5 +/- 3.2; P = 0.003), whereas no change in vitality score
      occurred in patients who did not continue GH therapy. The change in the energy
      subsection of the NHP and vitality subsection of the PGWB over the 9 years of the
      study were significantly different between the patients who opted to continue GH
      replacement and those who discontinued therapy (P = 0.008 and P < 0.001,
      respectively). CONCLUSION: During this 9-year study, small but significant
      declines in health were observed in GH-deficient adults who remained untreated.
      By contrast, the patients who received GH continuously experienced improvements
      in energy levels while all other areas of QoL were maintained. The beneficial
      effects of GH on QoL are therefore maintained with long-term GH replacement and
      obviate the reduction in QoL seen over time in untreated GH-deficient adults.

PMID- 12201830
TI  - Transdermal oestradiol replacement therapy enhances platelet constitutive nitric
      oxide synthase activity in postmenopausal women with type 2 diabetes mellitus.
AB  - OBJECTIVE: To determine whether treatment with transdermal oestrogen replacement
      therapy (TERT) in postmenopausal women with type 2 diabetes mellitus was able to
      increase the activity of constitutive nitric oxide synthase (cNOS) in platelets.
      RESEARCH DESIGN AND METHODS: Eighteen postmenopausal women with type 2 diabetes
      mellitus (group A) were studied in basal conditions (A1) and on the 10th day of
      the third month of a sequential opposed TERT (A2) evaluating platelet cNOS
      activity measured by the conversion of radiolabelled l-arginine to l-citrulline.
      As a control group (B) 25 normal postmenopausal women underwent the same
      treatment (B1 and B2 before and during treatment, respectively). RESULTS: Basal
      values of platelet cNOS activity were superimposable (0.6 +/- 0.1 vs. 0.7 +/- 0.1
      fmol/min/109 plts, NS). During TERT, platelet cNOS activity rose in A and B (0.6
      +/- 0.1 vs. 1.8 +/- 0.1 fmol/min/109 plts, P < 0.05 and 0.7 +/- 0.1 vs. 2.4 +/-
      0.2, P < 0.001, A1 vs. A2 and B1 vs. B2, respectively). However, platelet cNOS
      activity of A2 did not reach the values of B2 (1.8 +/- 0.1 vs. 2.4 +/- 0.2
      fmol/min/109 plts, P < 0.05; A2 vs. B2, respectively). CONCLUSIONS: Sequential
      opposed transdermal oestrogen replacement therapy was able to increase platelet
      cNOS activity in postmenopausal women with type 2 diabetes mellitus, suggesting
      that its use might be positive in preventing cardiovascular pathologies.

PMID- 12201831
TI  - A single growth hormone (GH) determination is sufficient for the diagnosis of GH
      deficiency in adult patients using the growth hormone releasing hormone plus
      growth hormone releasing peptide-6 test.
AB  - BACKGROUND: The diagnosis of GH deficiency in adults is based on the provocative
      testing of GH secretion. When testing a patient with suspected GH deficiency,
      clinicians assess the whole secretory curve and select the GH peak as an index of
      secretory capability. This procedure is time consuming and the determination of
      GH in several samples is necessary. The combined administration of growth hormone
      releasing hormone (GHRH) plus growth hormone releasing peptide-6 (GHRP-6) is an
      effective test of GH secretion, and it has been unambiguously demonstrated that
      the elicited GH peak is capable of segregating normal GH secretion subjects from
      GH deficient patients on an individual basis. The GHRH + GHRP-6 test
      biochemically classifies patients into three groups; those with a stimulated GH
      peak >/= 20 micro g/l are considered normal and those with peaks at </= 10 micro
      g/l as GH deficient. The group comprising individuals between these parameters is
      considered uncertain, and the results are further interpreted according to
      clinical information, or by other tests. OBJECTIVE: As the GHRH + GHRP-6 test
      induces GH peaks consistently in the first 30 minutes, the working hypothesis
      assessed in this study was whether a single determination of GH 30 minutes after
      stimulus could provide the same clinical classification as the whole secretory
      curve. PATIENTS AND METHODS: Three hundred and forty-nine adult subjects (146
      patients with organic pituitary disease and 203 healthy subjects) were studied.
      All were administered GHRH 1 micro g/kg i.v. plus GHRP-6 1 micro g/kg i.v. at 0
      minutes, and blood samples were obtained at regular intervals. GH was determined
      in all samples. RESULTS: GHRH + GHRP-6-evoked GH peaks in controls and patients
      were not correlated with GH basal values, making this determination useless for
      test validation. In contrast, an excellent correlation was observed between GH
      values at 30 minutes and the GH peaks (r = 0.994, P < 0.0001). When comparing the
      30-minute GH values against the peaks, the biochemical classification changed
      from normal toward uncertain in only five out of 203 control subjects, which is
      without clinical relevance according to Bayes theorem. Similarly, when the 30
      minute value was used instead of the peak in GH deficient patients, only two out
      of 146 patients moved from the uncertain area toward the GH deficient one. Thus,
      better diagnostic classification was provided for patients. CONCLUSIONS: The GHRH
      + GHRP-6 test is a convenient, safe and reliable, provocative test of GH reserve
      in adults, which can be reduced to a single fixed GH determination 30 minutes
      after stimulus.

PMID- 12201832
TI  - Effects of a growth hormone receptor antagonist on bone markers in acromegaly.
AB  - OBJECTIVE: Excess GH secretion, as occurs in acromegaly, is associated with
      abnormalities in bone turnover markers and bone mineral density (BMD). GH
      administration in GH deficient patients causes an increase in bone turnover. IGF
      I mediates many of the metabolic actions of GH, although GH may have direct
      effects upon bone. In patients with acromegaly who are treated with a GH receptor
      antagonist, selective blockade of the GH receptor results in a decrease in
      circulating IGF-I levels in the majority of cases. We hypothesized that, in
      acromegaly, antagonism of GH receptors would result in a decrease in serum
      markers of bone turnover, including serum procollagen I carboxy-terminal
      propeptide (PICP), osteocalcin and N-telopeptide (NTx). DESIGN AND SUBJECTS:
      Twenty-seven patients with acromegaly were enrolled as part of a multicentre 12
      week trial of a GH receptor antagonist and were randomized to placebo (n = 7) or
      10, 15 or 20 mg of pegvisomant (n = 20). MEASUREMENTS: Serum markers of bone
      turnover were determined at baseline and 12 weeks. RESULTS: Baseline bone
      turnover markers were above the upper limit of normal in 23%, 19% and 32% of
      subjects for osteocalcin, PICP and NTx, respectively. During the 12-week placebo
      controlled period, there were significant decreases in serum markers of bone
      formation, osteocalcin (-2.2 +/- 0.44 vs. placebo +0.01 +/- 0.39 nmol/l, P =
      0.009) and PICP (-23.6 +/- 9.6 vs. placebo +18.1 +/- 12.8 micro g/l, P = 0.022)
      and a serum marker of bone resorption, NTx (-4.4 +/- 1.4, placebo +1.0 +/- 0.3
      nm, P = 0.024). CONCLUSIONS: Using a specific GH receptor antagonist, we found
      that normalization of IGF-I is associated with rapid reductions in markers of
      both bone formation and resorption, and that these processes remain coupled.
      These data confirm the highly significant effects of GH and IGF-I in modulating
      bone turnover. The independent contributions of GH and IGF-I to these effects and
      the long-term effects on BMD in this population remain to be determined.

PMID- 12201833
TI  - Malnutrition, zinc supplementation and catch-up growth: changes in insulin-like
      growth factor I, its binding proteins, bone formation and collagen turnover.
AB  - OBJECTIVE: Zinc may be a limiting factor in restricting catch-up growth in
      severely malnourished children. This study had two aims: (i) to examine the
      effect of different zinc supplementation regimens on IGF-I, its binding proteins
      and on markers of bone and collagen turnover in severely malnourished children
      and (ii) to investigate mechanisms underlying catch-up growth by examining
      changes in these markers during nutritional rehabilitation, their inter
      relationships and their relationships with ponderal and linear growth. DESIGN:
      Double-blind randomized intervention study of three regimens of oral zinc
      supplementation. PATIENTS: One hundred and forty-one children, aged 6-36 months,
      mean (SD) age 15.4 (8.7) months, with day 1 weight-for-height SD score (whz) -2.6
      (0.93) and height-for-age SD score (haz) -3.79 (1.29). MEASUREMENTS: Weight,
      height, lower leg length (by knemometry) at 15-day intervals from day 1 to day 90
      of nutritional rehabilitation. Blood collection on days 1, 15 and 30 for IGF-I,
      IGFBP3, IGFBP2, bone alkaline phosphatase (BAP, osteoblast marker), procollagen
      type I C-terminal propeptide (PICP, marker of type I collagen synthesis),
      procollagen type III N-terminal propeptide (P3NP, marker of soft tissue type III
      collagen synthesis) and type I collagen telopeptide (ICTP, marker of type I
      collagen breakdown). RESULTS: There was early rapid weight gain during refeeding,
      whereas height gain occurred later in the trial. IGF-I, IGFBP3, BAP, PICP and
      P3NP were low or very low on day 1 compared to well-nourished age-matched
      European children, and all increased within 15 days (P < 0.001), with PICP and
      P3NP reaching levels higher than European norms. IGFBP2 and ICTP were high on day
      1 and decreased over the same period (P < 0.001). There were no differences in
      anthropometric outcome or marker responses among zinc regimens. Day 1 whz was
      correlated with BAP, PICP and P3NP (P < 0.001). Changes in IGF-I, IGFBP3, BAP,
      PICP and P3NP over 30 days correlated with ponderal growth (whz change) over the
      same period (all P < 0.01). However, changes in these markers over 30 days
      correlated better with lower leg growth (all P < 0.01) and linear growth (haz
      change, P < 0.01 for PICP and P3NP, P < 0.05 for IGFBP3) measured over 90
      compared with 30 days. At most time points, there were strong positive
      correlations (i) among IGF-I, IGFBP3, BAP, PICP and P3NP (P < 0.01) and (ii)
      between IGFBP2 and ICTP (P < 0.01). Conversely, IGFBP2 was negatively correlated
      with IGF-I, IGFBP3, BAP, PICP and P3NP at most time points (P < 0.01).
      CONCLUSIONS: We found no difference among zinc regimens in growth, IGF-I and its
      binding proteins or markers of bone and collagen turnover. Severe malnutrition
      was associated with low rates of bone and collagen synthesis and high rates of
      collagen degradation, and nutritional rehabilitation was associated with full or
      partial 'normalization' of the markers studied. Early weight gain and subsequent
      linear growth were associated with early increments in IGF-I, IGFBP3 and markers
      of bone and collagen formation. The study of these markers has provided
      additional insights into the mechanisms of the effects of malnutrition and
      refeeding on growth.

PMID- 12201834
TI  - The treatment of a thyrotropin-secreting pituitary macroadenoma with octreotide
      in twin pregnancy.
AB  - TSH-secreting pituitary tumours are rare but difficult to treat due to a
      combination of refractory hyperthyroidism and low surgical cure rates. We
      describe the case of a 21-year-old woman who, despite twin pregnancy, became
      euthyroid and had dramatic tumour shrinkage on octreotide treatment. To our
      knowledge, this is the first description of the use of octreotide for a TSH
      secreting pituitary adenoma throughout pregnancy.

PMID- 12201835
TI  - Neonatal thyrotoxicosis and maternal infertility in thyroid hormone resistance
      due to a mutation in the TRbeta gene (M313T).
AB  - We report two unusual cases of resistance to thyroid hormone (RTH) in one family.
      The first case, a male infant, had clinical features of thyrotoxicosis in the
      neonatal period. In the fourth week of life weight gain was poor despite a daily
      intake of standard infant formula almost double the infant's estimated
      requirements. At this time serum free T4 (fT4) was 60.7 pmol/l (Normal range [NR]
      11-25 pmol/l) and TSH was inappropriately normal at 1.8 mU/l (NR 0.3-4.0 mU/l).
      The infant responded clinically and biochemically to propylthiouracil (PTU) at a
      dose of 10 mg/kg/day. Following 27 days of treatment serum fT4 was 22.6 pmol/l
      and TSH had risen to 24.9 mU/l. As the infant was thriving treatment was
      discontinued. The infant, now aged 6 months old, remains clinically euthyroid and
      developmentally normal off treatment. The infant's mother, from whom he had
      inherited a mutation of the thyroid receptor beta (TRbeta) gene (M313T),
      presented earlier with secondary infertility and clinical features of
      thyrotoxicosis. Treatment with PTU restored her fertility and she spontaneously
      conceived. In the subsequent pregnancy, clinical and biochemical features of RTH
      improved, and she gave birth to a small but healthy female infant. In the next
      pregnancy, resulting in the birth of the affected male infant, clinical and
      biochemical features of RTH worsened, and high doses of PTU were required to
      maintain a clinically euthyroid state. To our knowledge, these are the first case
      reports of RTH associated with added features of a hypermetabolic state in
      infancy and secondary infertility.

PMID- 12201836
TI  - Insulin autoimmune syndrome in a patient with viral hepatitis C.

PMID- 12201837
TI  - Molecular defects in coagulation Factor VIII and their impact on Factor VIII
      function.
AB  - Molecular defects in Factor VIII (FVIII), such as haemophilia A-related mutations
      or denaturative conformational changes, may affect the stability of FVIII as well
      as its interactions with physiological activators, von Willebrand Factor,
      phospholipid, or conformationally sensitive antibodies. We summarize the
      contemporary assays which allow identification of impaired functional
      interactions of FVIII that cause a reduction or loss of its cofactor activity
      and/or increased immunogenicity. These assays can potentially be used for
      detection of molecular defects in FVIII and elucidation of the function impaired
      by these defects.

PMID- 12201838
TI  - Knowledge about blood donation among a sample of Thai university students.
AB  - BACKGROUND AND OBJECTIVES: Blood banks in Thailand use only a voluntary donation
      system. Although this has been established for many years, the quantity of blood
      is still insufficient. Knowledge about blood donation and attitudes toward it are
      inadequate, especially in rural areas. The registry data of the National Blood
      Centre, Thai Red Cross Society, indicate that most voluntary blood donors are
      university students. The present study was therefore conducted among the students
      of Chulalongkorn University to assess their knowledge of voluntary, non
      remunerated blood donation. MATERIALS AND METHODS: Four hundred students
      participated in this study. A self-administered questionnaire and face-to-face
      interview on various aspects of blood donation were used for data collection.
      RESULTS: Although most participants (80%) knew about blood donation, only 11% (44
      subjects) had ever donated blood voluntarily. We found no significant correlation
      between demographic data (gender, age, educational level of subjects studied) and
      such knowledge or actual blood donation. Among the non-donor respondents, fear
      (305 cases) was the most common reason for not donating blood. CONCLUSIONS:
      Greater knowledge about blood donation does not lead to donation. Therefore,
      specific campaigns are needed to convert this into actual voluntary donation.

PMID- 12201839
TI  - The development of a national standardized approach for the enumeration of
      residual leucocytes in blood components.
AB  - BACKGROUND AND OBJECTIVES: The UK Blood Transfusion Services implemented
      universal leucocyte depletion of the blood supply in November 1999. To provide
      statistical process monitoring of these processes, automated methods were
      introduced to count residual leucocytes (white blood cells) in blood components.
      MATERIALS AND METHODS: Initially in the National Blood Service (NBS) England,
      protocols were standardized on the use of LeucoCount reagents with either Becton
      Dickinson or Beckman Coulter flow cytometers. RESULTS: Standardization of
      protocols resulted in a decreased intersite variability of red cell samples (from
      36% to 9% at a level of 11 and 10 cells/ micro l, respectively), and 100% of
      sites (n = 11) fulfilled the validation criteria. However, we also evaluated the
      use of alternative reagents with the result that reagents from either Becton
      Dickinson or Beckman Coulter, used on either a Becton-Dickinson or Beckman
      Coulter flow cytometer, passed our validation criteria. CONCLUSIONS: It is
      critical to include samples from filtered products containing white blood cells
      in validations of leucocyte enumeration methodology, as results may differ
      between methods using these samples but not using spiked or fixed material.
      Standardized gating strategies and optimization methods for flow cytometers are
      critical for obtaining equivalent results with different reagents and
      instruments.

PMID- 12201840
TI  - Value of central analysis of leucocyte depletion quality control data within the
      National Blood Service, England.
AB  - BACKGROUND AND OBJECTIVES: The results of quality monitoring leucocyte counts
      were analysed nationally for the first 2 years of universal leucocyte depletion
      (LD), spanning the time-period before and after standardization of the counting
      and LD methods. The objectives were twofold: first to determine whether the
      implementation strategy was effective in achieving the LD specification (< 5 x
      10(6) leucocytes in 99% of components with 95% statistical confidence); and
      second, whether quality monitoring was able to detect potential non-conformance.
      MATERIALS AND METHODS: Residual leucocytes were counted using Beckman Coulter or
      Becton Dickinson (BD) flow cytometers and reagents. Data were collected into
      standardized analysis software (NWA Quality Analyst) for local trend analysis and
      checks for conformance to process specification, and collated centrally. Analysis
      was performed for six time-periods between January 1999 and March 2001.
      Specification failures were analysed to determine the likelihood of extreme
      failure. Statistical process monitoring was adjusted to suit LD processes.
      RESULTS: Data from red cells in optimal additive solution (OAS), filtered either
      as whole blood or red cell concentrates, and platelet pools improved
      significantly over the 2-year period with specification failures falling from
      0.35%, 0.48% and 0.56%, respectively, in January-June 1999 to 0.06%, 0.01% and
      0.04% in January-March 2001. Specification failures in red cells in OAS LD for
      the period January-December 2000 showed only 0.02% with a leucocyte count of > 30
      x 10(6)/unit. Extreme failures are now very rare. Monitoring methods have been
      effective in detecting process change and drift. CONCLUSION: LD performance
      varies between different LD systems, but monitoring has proved sufficiently
      robust to detect processes that perform poorly. The chosen specification has been
      both achievable and appropriate to the systems in use. Standardization of the
      counting method is central to the ability to monitor and analyse results
      effectively across the whole service.

PMID- 12201841
TI  - Prestorage leucocyte reduction of red cell components prevents release of
      bactericidal permeability increasing protein and defensins.
AB  - BACKGROUND AND OBJECTIVES: In this study we examined whether prestorage leucocyte
      reduction prevents the accumulation of bioreactive substances in red cell units.
      MATERIALS AND METHODS: Measurements were performed in the supernatants of buffy
      coat-depleted (standard red cells) and leucocyte-reduced (filtered red cells) red
      cell units. The effect of storage was evaluated by taking repetitive samples up
      to 35 days after donation. We determined the concentrations of polymorphonuclear
      neutrophil (PMN)-derived bactericidal permeability increasing protein (BPI),
      defensins and annexin A5. In addition, leucocyte counts (using nageotte chamber)
      were performed on days 0 and 35. RESULTS: During storage, the concentrations of
      BPI, defensins and annexin A5 in standard red cells gradually increased. However,
      in the filtered red cells BPI and defensins were found in only a few samples,
      whereas the annexin A5 concentration in these units did not change during
      storage. Haemolysis data in both types of red cell components were similar at all
      time-points, except prestorage. Significant correlations were found between the
      release of BPI, defensins and annexin A5 into red cell units and the loss of
      leucocytes during storage. CONCLUSIONS: PMNs lose their membrane integrity during
      cold storage and release their contents into red cell components. Prestorage
      leucocyte reduction of red cell components prevents the accumulation of BPI,
      defensins and annexin A5.

PMID- 12201842
TI  - Cytokine levels as performance indicators for white blood cell reduction of
      platelet concentrates.
AB  - BACKGROUND AND OBJECTIVES: With the implementation of universal white blood cell
      (WBC) reduction in the UK, in-process WBC-reduction filters for pooled buffy coat
      (BC)-derived platelet concentrates (PCs) and apheresis methods are used routinely
      for the production of WBC-reduced PCs. While these strategies meet the
      specification for WBC reduction (< 5 x 10(6) WBCs/unit), the products from these
      processes may differ depending on the process employed and its performance. The
      aim of this study was therefore to investigate whether PCs prepared using various
      WBC-reduction processes are sufficiently depleted of WBCs to limit cytokine
      accumulation during storage and to assess if cytokine levels detected in platelet
      products can serve as indicators of acceptable platelet activation as a result of
      the WBC-reduction process. MATERIALS AND METHODS: We measured the levels of
      cytokines predominantly derived from WBCs [e.g. interleukin-8 (IL-8)] and
      platelets [e.g. regulated on activation, normal, T-cell expressed, and secreted
      (RANTES) and transforming growth factor-beta(1) (TGF-beta(1))] under the present
      experimental conditions in different WBC-reduced PCs, i.e. PCs prepared from
      three different WBC-reduction filters and control non-filtered PCs using pooled
      BCs from the same donors and three apheresis types. Supernatant plasma was
      collected at the beginning (day 1) and end (day 5) of the shelf life of each PC,
      and the cytokine content was determined using appropriate enzyme-linked
      immunosorbent assays (ELISAs). Process efficiency was assessed by platelet yield
      and residual WBC count. RESULTS: We found that products from the apheresis
      process involving a filtration step (Haemonetics MCS+) showed a lower cytokine
      content on both day 1 and day 5 in comparison with the fluidized bed (COBE
      Spectra) or elutriation (Amicus) processes. WBC reduction of BC-PCs of the same
      origin using three different filters showed comparable levels of cytokines on day
      1 in all units. After storage for 5 days, the levels of IL-8 remained essentially
      unchanged in filtered BC-PCs but increased by more than threefold in control non
      filtered BC-PCs, suggesting IL-8 release by residual WBCs present in the control
      PCs. The concentration of platelet-derived cytokines such as RANTES and TGF
      beta(1), however, increased significantly in all filtered and control non
      filtered PCs during the storage period. CONCLUSION: These results show that
      markers of cytokine release from both WBCs and platelets are useful indicators of
      the performance and efficacy of the WBC-reduction process and of platelet
      quality.

PMID- 12201843
TI  - Studies on the removal of a bovine spongiform encephalopathy-derived agent by
      processes used in the manufacture of human immunoglobulin.
AB  - BACKGROUND AND OBJECTIVES: There is still uncertainty over how the agent of
      variant Creutzfeld-Jakob disease (vCJD) would partition during the manufacture of
      plasma derivatives. In this study, a BSE-derived agent was used as a vCJD model
      to determine the extent to which infectivity could be removed by selected steps
      used in the manufacture of intravenous immunoglobulin (IVIG). MATERIALS AND
      METHODS: Murine-passaged BSE (strain 301V), in the form of a microsomal fraction
      prepared from infected brain, was used to "spike" the starting material in three
      experiments. The partitioning of BSE infectivity was measured over Fraction I+III
      precipitation, borosilicate microfibre depth filtration and Seitz depth
      filtration, with these steps being examined individually and in series. RESULTS:
      Most 301V infectivity partitioned into Fraction I+III (log reduction 2.1).
      Infectivity remaining in Supernatant I+III was reduced by AP20 glass-fibre depth
      filtration (log reduction 0.6) and subsequently removed to below the limit of
      detection by Seitz KS80 depth filtration, giving an overall log reduction of > or
      = 2.9 for the three steps in series. By contrast, glass-fibre depth filtration
      gave a log reduction of 2.4 when challenged directly with "spiked" feedstock.
      Seitz KS80 depth filtration gave a log reduction of > or = 3.1 when challenged
      directly with 'spiked' feedstock and also removed residual infectivity to below
      the limit of detection when applied as the final step in series. CONCLUSIONS:
      Results using a BSE-derived agent suggest that vCJD infectivity should be
      substantially removed from immunoglobulin G (IgG) solutions by Fraction I+III
      precipitation and Seitz KS80 depth filtration. The three different process steps
      examined acted in a complementary manner to one another when operated in series.
      However, the data demonstrated that it would be inappropriate to add together the
      reduction factors that had been derived for each step in isolation.

PMID- 12201844
TI  - Pharmaco-economics of blood transfusion safety: review of the available evidence.
AB  - BACKGROUND AND OBJECTIVES: Pharmaco-economics provides a standardized methodology
      for valid comparisons of interventions in different fields of health care. The
      role of pharmaco-economics in the safety of blood and blood products has,
      however, been very limited to date. This review discusses the pharmaco-economic
      evaluations of strategies to enhance blood product safety that have been
      published in the scientific literature. MATERIALS AND METHODS: We reviewed
      pharmaco-economic methodology with special reference to cost-effectiveness
      analysis. We searched the literature for cost-effectiveness in blood product
      safety. RESULT: Net costs per quality adjusted life-year (QALY) gained varied
      from cost-saving for human immunodeficiency virus (HIV)- and hepatitis C virus
      (HCV) antibody screening and leucoreduction to several million US dollars per
      QALY gained for solvent-detergent treatment of plasma, nucleic acid amplification
      testing and HIV p24 antigen testing. CONCLUSIONS: To date the safety of blood
      transfusion has been largely determined by available technology, irrespective of
      pharmaco-economics. Net costs up to several million US dollars per QALY gained
      were found for interventions implemented.

PMID- 12201845
TI  - Molecular background of Rh D-positive, D-negative, D(el) and weak D phenotypes in
      Chinese.
AB  - BACKGROUND AND OBJECTIVES: The aim of this study was to elucidate the genetic
      background of D-negative and D(el) in the Chinese population. MATERIALS AND
      METHODS: We investigated nine D-positive, 76 D-negative, 26 D(el) and three weak
      D Chinese individuals by amplification and sequencing of the complete coding
      region of the RHD gene from genomic DNA. A new RHD polymerase chain reaction with
      sequence-specific primers (PCR-SSP) method was developed with optimized
      specificity for typing Chinese individuals. RESULTS: In D-positive samples the
      RHD sequence was in complete concordance with RHD in other populations. In 12 of
      76 (15.8%) D-negative individuals we detected regions of RHD. Three new alleles
      were found. All 26 D(el), as well as two weak D, individuals carried an RHD 1227A
      allele. In the remaining weak D sample we identified a weak D type 15.
      CONCLUSIONS: It should now be possible to correctly predict the RhD phenotype in
      Chinese subjects. D(el) can also be designated as a particular weak D type.

PMID- 12201846
TI  - Immunological characterization of anti-Mi(a), a red blood cell alloantibody, in
      Taiwan.
AB  - BACKGROUND AND OBJECTIVES: The red blood cell Mi III phenotype is prevalent in
      Asia, and its corresponding alloantibody, anti-Mi(a), has been reported to cause
      haemolytic transfusion reactions and haemolytic disease of the newborn. However,
      a complete picture of the immunological characteristics of anti-Mi(a) is still
      lacking. We therefore conducted a systematic study to evaluate the potential
      clinical significance of this antibody. MATERIALS AND METHODS: From April 1999 to
      March 2000, we identified 60 sera containing anti-Mi(a) among pretransfusion
      samples at a teaching hospital in Taiwan. These antibodies were tested for
      immunoglobulin class, thermal range and activity in a monocyte monolayer assay.
      RESULTS: Thirty-four (57%) of the antibodies were immunoglobulin M (IgM), and 15
      retained their activity at 37 degrees C. Of those that were immunoglobulin G
      (IgG), 96% were of subclasses IgG1 and/or IgG3. Monocyte monolayer assay studies
      showed that 69% (18/26) of the IgG anti-Mi(a) sera were reactive. CONCLUSIONS:
      Our study justifies the implementation of anti-Mi(a) screening in Taiwan.

PMID- 12201847
TI  - A second case of post-transfusion purpura caused by HPA-5a antibodies: successful
      treatment with intravenous immunoglobulin.
AB  - Post-transfusion purpura (PTP) is a rare disorder characterized by severe
      thrombocytopenia developing seven to 10 days following transfusion of platelet
      containing blood components, in a person who was previously sensitized via
      transfusion or pregnancy. Although most cases of PTP are caused by alloantibodies
      directed against HPA-1a[(Pl(A1))], this case represents the second example of
      anti-HPA-5a-associated PTP. A 61-year-old female was diagnosed with acute
      myocardial infarction and gastrointestinal bleeding and, after receiving six
      units of packed red cells over 5 days, developed PTP as a result of HPA-5a
      [Br(b)] antibodies with severe thrombocytopenia (5000/microl). She was
      successfully treated with intravenous immunoglobulin (IVIG), suggesting that this
      is a highly effective mode of treatment for PTP, regardless of the antibody
      implicated.

PMID- 12201848
TI  - Detection of parvovirus B19 DNA in solvent-detergent plasma.

PMID- 12201850
TI  - Response times of donors sent letters requesting them to contact the Welsh blood
      service.

PMID- 12201851
TI  - Improved polymerase chain reaction-based glycophorin-A M/N blood group
      allelotyping.

PMID- 12201852
TI  - International forum. Use of umbilical cord blood progenitor cells as an
      alternative for bone marrow transplantation.

PMID- 12201853
TI  - Consensus statement from the consensus conference on blood-borne human
      immunodeficiency virus and hepatitis: optimizing the donor-selection process.

PMID- 12201855
TI  - The bleeding edge of decision making in managed health care--Kaiser-Permanente's
      model for formulary development.

PMID- 12201856
TI  - FDA actions against misleading or unsubstantiated economic and quality-of-life
      promotional claims: an analysis of warning letters and notices of violation.
AB  - OBJECTIVES: The objective of this study was to understand the types of economic
      and quality-of-life promotional claims the FDA considers false or misleading.
      METHODS: Publicly available FDA letters (n = 569) sent to pharmaceutical
      companies from 1997 through 2001 for inappropriate promotional claims were
      reviewed. A standard data collection form was developed, including six categories
      for economic violations and three for QOL violations. For QOL, only letters with
      explicit violations for false or misleading claims using the words "quality of
      life" or patient "well-being" were considered. Other information collected
      included type of regulatory letter and media in which violations were found.
      RESULTS: Twenty-eight (4.9%) letters cited false and/or misleading economic
      claims. The most common economic violation was "unsupported comparative claim of
      effectiveness, safety, or interchangeability" (n = 14). Twenty-eight (4.9%)
      letters cited QOL violations, of which four contained both economic and QOL
      violations. The most common QOL violation was "lack of substantial evidence for
      QOL claims" (n = 15). None of the FDA letters used the term "patient reported
      outcomes." Violations were found most frequently in brochure and Web site-based
      promotions. CONCLUSIONS: The body of evidence that is emerging illustrates how
      the FDA is regulating promotional material containing misleading or
      unsubstantiated economic and QOL claims. However, knowing what constitutes an
      appropriate claim remains challenging because there are no formal guidelines
      describing what constitutes a violation, nor what level of substantiating
      evidence is required. More guidance may be needed to ensure appropriate use of
      these claims in drug promotions.

PMID- 12201857
TI  - Bootstrap confidence intervals for costs-of-illness of type 2 diabetes mellitus
      in Germany.
AB  - OBJECTIVE: The Costs of Diabetes in Europe-Type 2 study (CODE-2, SmithKline
      Beecham plc) measures costs of managing patients with type 2 diabetes mellitus in
      Germany. The aim of this analysis was to assess the uncertainty of these
      estimates. DESIGN AND SETTING: The German study arm was based on a sample of 809
      patients with type 2 diabetes registered in general practices. Information on
      socioeconomic data, medical resource use, and clinical data was collected
      retrospectively for 1998. PATIENTS AND PARTICIPANTS: Patients were grouped in
      five strata based on their complication status, because of the high impact of
      complications on costs. To obtain higher credibility of resulting estimates, rare
      complication groups were overrepresented. To be representative, results were
      weighted using real prevalence data on complications from a prestudy. MAIN
      OUTCOME MEASURES AND RESULTS: Within each stratum, results were calculated as
      arithmetic mean except for demographic data, where the median was applied as
      input for weighted averages. Because the degree of precision of calculated
      estimates was not accessible analytically, 95% confidence intervals (CIs) were
      computed via bootstrapping of 10,000 independent bootstrap samples for each of
      the calculated estimates. All costs are given for the payers' perspective in
      German Deutsche Mark (DM). Costs per patient and year for ambulatory care were DM
      775 with 95% CI (721-835), for hospitalizations DM 2771 (2242-3342), for drug
      treatment DM 1496 (1399-1598), and for rehabilitation DM 120 (70-177). The
      indirect cost was DM 372 (144-645). From the perspective of the sickness funds,
      cost per patient and year was DM 5539 (5184-5894). Mean HbA1c status was 7.51%
      (7.37-7.66) with the majority of patients not achieving glycemic control below
      6.5%. CONCLUSION: Bootstrap CIs are remarkably narrow. Combining a weighted
      stratification with bootstrap estimation is an appropriate method for analyzing
      the weighted average of highly variable and skewed parameters such as costs of
      diabetes.

PMID- 12201858
TI  - The cost-effectiveness of alternative therapeutic strategies for the management
      of chronic hepatitis B in Poland.
AB  - OBJECTIVE: The aim of the study was to estimate the cost-effectiveness of
      alternative therapeutic strategies for the management of chronic hepatitis B
      (CHB) in Poland. METHODS: The model for the Polish health-care context was based
      on clinical data from the literature and local data on health-care resource
      utilization and unit costs. Costs and effects of a population of CHB patients
      were modeled using four scenarios, which attempt to reflect real-life practice in
      which patients may receive any of the treatment options available and in which a
      proportion of patients may still receive no treatment because therapy is not
      suitable. Strategies A and B assumed the availability of both treatment options:
      the first choice of treatment is in A, lamivudine, and in B, interferon alpha
      (IFN-alpha). In strategy C, the only approved treatment is IFN-alpha, and in
      strategy D, the patients receive no antiviral treatment. The outcome measures
      were HBeAg seroconversion and nonprogression to cirrhosis-the surrogate marker
      with predictive value for improved survival. Only direct medical costs were
      analyzed. The payer's perspective and time horizon of 1 year were adopted. One
      way sensitivity analysis and extreme scenario analysis were performed. RESULTS:
      The best results in terms of seroconversion and nonprogression to cirrhosis were
      achieved for strategy A, costs were lowest for strategy D, and strategies B and C
      were dominated by strategy A. The incremental cost/effectiveness ratio (ICER)
      comparing strategy A with strategy D was 57,855 Polish new zloty (PLN) per extra
      seroconversion and 79,550 PLN per cirrhosis case avoided. CONCLUSIONS: Cirrhosis
      reduces estimated life expectancy by 37.76 years and by 20 years among 30- and 50
      year-olds, respectively. The ICER for strategies A and D was 2105 PLN and 3978
      PLN per life-years gained for the population at ages 30 and 50, respectively, and
      was below the suggested threshold for cost-effectiveness, based on treatment
      costs for 1 year of hemodialysis in Poland (62,400 PLN). Changing the value of
      key drivers for sensitivity analysis did not have a significant effect on the
      ICER.

PMID- 12201859
TI  - Validation of the Patient Perception of Migraine Questionnaire.
AB  - OBJECTIVE: The purpose of this study was to assess the psychometric properties of
      the Patient Perception of Migraine Questionnaire (PPMQ), which measures patient
      satisfaction with migraine therapy. METHODS AND DATA: The PPMQ was administered
      to 940 patients as part of a 3-month, multinational, open-label, clinical trial
      comparing the effects of oral naratriptan 2.5 mg with the patient's customary
      therapy for the treatment of migraine. Psychometric properties of the PPMQ were
      evaluated in terms of its latent factor structure, validity, reliability,
      sensitivity, and development of a scoring method. Classical Test theory and Item
      Response theory (IRT) modeling were both used to measure reliability. RESULTS:
      The PPMQ was able to detect treatment differences (P >.001), and all items
      significantly correlated with diary ratings of headache pain (r =.18-.51, p
      >.0001) and the Medical Outcomes Short Form-36 pain scale (r =.27, p >.0001). A
      principal components factor analysis revealed that the items on the PPMQ were
      psychometrically distinct and unidimensional (loadings, 0.74-0.91), with the
      exclusion of two items. The reliability (i.e., internal item consistency) of the
      PPMQ post-trial was high in both treatment groups (Cronbach's alpha = 0.96). An
      IRT analysis also ensured the formation of homogenous items, which were stable on
      repeat administration. Items did not require weighting and can be simply summed
      to yield a total score. CONCLUSION: Based on the data from this one clinical
      trial, the 15-item PPMQ was shown to be a valid and reliable instrument that
      seems to efficiently and comprehensively measure patient perception of drug
      attributes in relation to the treatment of symptoms associated with migraine
      headaches.

PMID- 12201860
TI  - Odds ratio, relative risk, absolute risk reduction, and the number needed to
      treat--which of these should we use?
AB  - INTRODUCTION: Statistical analyses of data and making sense of medical data have
      received much attention in the medical literature, but nevertheless have caused
      confusion among practitioners. Each researcher provides a different method for
      comparing treatments. For example, when the end point is binary, such as disease
      versus no disease, the common measures are odds ratios, relative risk, relative
      risk reduction, absolute risk reduction, and the number needed to treat. The
      question faced by the practitioner is then: Which one will help me in choosing
      the best treatment for my patient? METHODS: The purpose of this paper is to
      illustrate, using examples, how each measure is used, what it means, and what are
      its advantages and disadvantages. RESULTS: Some pairs of measures present
      equivalent information. Furthermore, it is shown that different measures result
      in different impressions. CONCLUSION: It is recommended that researchers report
      both a relative and an absolute measure and present these with appropriate
      confidence intervals.

PMID- 12201861
TI  - Comparative analysis of two quality-of-life instruments for patients with chronic
      obstructive pulmonary disease.
AB  - OBJECTIVE: The St. George's Respiratory Questionnaire (SGRQ) has been validated
      and widely used in assessing quality of life among patients with chronic
      obstructive pulmonary disease (COPD), but it is time-consuming and complicated to
      score. A more concise instrument, the Airways Questionnaire (AQ), was developed
      to measure quality of life (QoL) among patients with asthma and COPD. The shorter
      version of this instrument has 20 items (AQ20) and the longer version has 30
      items (AQ30). The purpose of this study was to determine the relationship between
      QoL scores measured by the AQ20/30 or the SGRQ scale and utilization of health
      care services by COPD patients and to evaluate the comparative advantage of any
      one of these instruments in measuring the QoL of COPD patients. METHODS: Results
      from a survey of 1000 patients participating in a pilot COPD health management
      program were used for this analysis. A total of 303 patients completed both the
      AQ20/30 and the SGRQ questionnaires. Logistic regression models were used to
      analyze the relationship between utilization of health care services and QoL
      scores while controlling for a set of covariates. Spearman's rank correlation was
      used to determine whether the AQ30 and the SGRQ scores for symptoms, activity,
      and impact, and the overall scores were correlated. RESULTS: The regression
      results demonstrate that there is a strong relationship between quality-of-life
      scores and health-care utilization variables. Moreover, the degree of association
      between the AQ20/30 scores and utilization variables and the SGRQ and utilization
      variables are comparable. Both the AQ20 and the AQ30 were highly correlated with
      the overall SGRQ score and with symptoms, activity, and impact component scores.
      CONCLUSION: The AQ20/30 and the SGRQ scores are comparable in terms of measuring
      QoL in COPD patients and are equally useful in determining the association
      between utilization of health-care services and QoL.

PMID- 12201862
TI  - Oxidative stress: does it 'initiate' hepatic stellate cell activation or only
      'perpetuate' the process?

PMID- 12201863
TI  - Cholangiocarcinoma: recent progress. Part 1: epidemiology and etiology.
AB  - An attempt is made in this review to update the reader on recent developments and
      progress in the study of cholangiocarcinoma: a major primary carcinoma of the
      liver with a very poor prognosis. Knowledge of the cell biology and physiological
      functions of the cholangiocyte has recently so progressed that our understanding
      of cholangiocarcinogenetic mechanism is expected to follow. The first part of the
      review deals with semantic problems, temporal changes in the incidence of
      cholangiocarcinoma and geographic differences in epidemiology, etiologic factors
      (particularly opistorchiasis in Thailand and hepatolithiasis in the Far East),
      and discusses a recently disclosed role of hepatitis C virus infection (30% of
      cholangiocarcinoma patients have antibodies against hepatitis C virus in Japan).

PMID- 12201864
TI  - Cholangiocarcinoma: recent progress. Part 2: molecular pathology and treatment.
AB  - Part 2 of this review discusses DNA damage in biliary epithelial cells in the
      development of cholangiocarcinoma, alterations in cell kinetics of biliary
      epithelial cells, biliary epithelial mitoinhibition, and apoptosis that includes
      the role of Bcl-2, transforming growth factor-beta, telomerase activities and
      deregulation of Ras and p53, cancer-associated antigens in cholangiocarcinoma,
      precancerous lesions, stroma formation and angiogenesis, cancer invasion, cell
      cell and cell-matrix interactions, and the mechanism of evasion from immune
      surveillance. These discussions are followed briefly by treatments such as
      photodynamic therapy, and surgical approaches comparing resection and liver
      transplantation.

PMID- 12201865
TI  - Pathology of fundic varices of the stomach and rupture.
AB  - BACKGROUND AND AIM: Gastric varices, the rupture of which can be a fatal
      complication of portal hypertension, have not been well documented
      histopathologically. While cardiac varices develop in continuity with esophageal
      varices, fundic varices develop independently, having characteristic
      pathophysiology. Elucidation of the angioarchitecture of fundic varices will
      facilitate future improvement of treatment. METHODS: Twelve stomachs with fundic
      varices, either resected or autopsied, were examined by injecting a barium
      gelatin solution into the vein that was forming varices, soft X-rayed for the
      study of the vessel course, and then the stomach made into transparent
      preparations for stereoscopic study. Five fundic varices with a recognizable
      rupture site were studied histologically. RESULTS: Fundic varices could be
      classified into two types: Type I, single vein forming the supplying vessel,
      varix and draining vessel without changing caliber (eight cases) or plural veins
      supplying the varix (one case) and; Type II, many branching vessels existing
      beside the main supplying and draining vessels (three cases). Fundic varices
      exist in the submucosa with no enlarged vein in the lamina propria, and rupture
      occurs through the portion of the varix that protrudes into the stomach lumen
      penetrating the muscularis mucosae and lamina propria. CONCLUSIONS: Fundic
      varices form with the supplying vessel, mostly singular, and the draining vessel
      is frequently a gastrorenal collateral. Fundic varices form in the submucosa,
      unlike esophageal varices, and perforate through the overlying muscularis mucosae
      and lamina propria.

PMID- 12201866
TI  - Expression of mRNA for glucocorticoid receptors in peripheral blood mononuclear
      cells of patients with Crohn's disease.
AB  - BACKGROUND: The amount of glucocorticoid (GC) receptors (GR) in immune cells
      might be critical for successful GC treatment of patients with Crohn's disease
      (CD). However, little is known about the expression of GR in CD; therefore, we
      carried out quantitative analyses for GR messenger (m)RNA expression in
      peripheral-blood mononuclear cells (PBMC) of CD. METHODS: Seventeen patients with
      CD and 33 healthy subjects entered into this study. We measured the GRalpha mRNA
      level in the PBMC of these subjects by a reverse transcription-competitive
      polymerase chain reaction procedure. Relative amounts for GRbeta mRNA were
      obtained semiquantitatively. RESULTS: The amounts of GRalpha-mRNA in the CD
      patients and healthy subjects were 0.053 +/- 0.052 and 0.130 +/- 0.108
      (copies/copies of beta-actin mRNA), respectively. The former value was
      significantly lower than that of the latter (P < 0.01). The rates of the CD
      patients and healthy subjects expressing GRbeta-mRNA in PBMC were 41.2% and
      45.5%, respectively, and there was no significant difference in the rates between
      the two groups (P = 0.339). However, the relative amounts of GRbeta-mRNA in the
      PBMC were estimated to be 1.053 x 10-5 +/- 2.540 x 10-5 for the CD patients, and
      1.872 x 10-5 +/- 3.252 x 10-5 (fluorescence intensity/copies of beta-actin mRNA)
      for the healthy subjects, and the former was significantly smaller than the
      latter (P < 0.05). Moreover, there was an inverse correlation between the
      duration of disease (year) and the amounts of GRalpha-mRNA in the PBMC of the CD
      patients (P < 0.05). CONCLUSIONS: The amounts of GRalpha-mRNA and GRbeta-mRNA in
      the PBMC of the CD patients were lower than those of the healthy subjects. The
      duration of disease correlated with decreased amounts of GRalpha-mRNA in the
      PBMC. Furthermore, the clinical significance of the GR-mRNA status in the PBMC
      remains to be elucidated.

PMID- 12201867
TI  - Dysplasia and carcinoma development in a repeated dextran sulfate sodium-induced
      colitis model.
AB  - BACKGROUND: As an important mechanism underlying the increased risk of colorectal
      carcinoma development in patients with long-standing ulcerative colitis,
      promotion as a result of the regenerative process has been proposed. In the
      present study, a dysplasia-carcinoma sequence in a novel repeated colitis model
      in mice is documented. METHODS: Repeated colitis was induced by nine
      administration cycles of 3% dextran sulfate sodium (DSS; molecular weight, 54
      000): each administration cycle comprised 3% DSS for 7 days followed by distilled
      water for the subsequent 14 days, to give conditions similar to the clinically
      observed active and remission phases in humans. RESULTS: Multiple colorectal
      tumors (nine low- and four high-grade dysplasias and two carcinomas) developed in
      25 mice. These neoplastic lesions consisted of tubular structures, presenting as
      various types of elevated, flat and depressed tumor, similar to those in
      ulcerative colitis patients. A time-course study with assessment of the severity
      of colitis and in vivo bromodeoxyuridine uptake during a single 3% DSS
      administration cycle revealed a high level of regenerative activity in the
      colitis-affected mucosal epithelia. CONCLUSION: Thus, with the present repeated
      colitis model, regeneration and neoplastic lesions were apparent, the biological
      features of which provide evidence of a colorectal dysplasia-invasive carcinoma
      sequence in ulcerative colitis.

PMID- 12201868
TI  - Minimal expression of the proto-oncogene int-2 encoded protein in a series of
      colorectal carcinomas.
AB  - BACKGROUND: Int-2 (fibroblast growth factor-3) is a gene that belongs to the
      fibroblast growth factor gene family. It has been implicated in the
      carcinogenesis of several types of cancer, including esophageal squamous cell
      carcinoma, breast, head, and neck and lung carcinomas; but no firm data on its
      biological activity regarding neoplasms arising from the glandular epithelia of
      the gastrointestinal tract exists. METHODS: In the present immunohistochemical
      study, we investigated the presence of int-2 encoded protein in a panel of 80
      cases of colon carcinoma of various stages, grades and sizes. A sheep antihuman
      int-2 antibody was applied to paraffin-embedded tissue sections from the tumor
      samples. The percentage of int-2 immunostaining in the positively stained
      specimens was evaluated by image analysis. RESULTS: Int-2 was positively detected
      in only four tumors (i.e. 5% of the cases examined). All immunopositive cases
      were moderately differentiated tumors; the adjacent mucosa did not express int-2
      protein. The relevant patients were male. CONCLUSION: These findings suggest that
      the role of int-2 in colorectal carcinogenesis is probably a limited one.

PMID- 12201869
TI  - Combination therapy for children with chronic hepatitis B virus infection.
AB  - BACKGROUND AND AIM: To compare the therapeutic efficacy of two different
      interferon (INF)-alpha and lamivudine (LAM) combination therapy regimens in
      childhood chronic hepatitis B (CHB) infections. METHODS: Thirty-two children with
      CHB infection were prospectively evaluated in two random groups. In the first
      group, patients received INF-alpha 10 MU/m2 and LAM 4 mg/kg (max 100 mg)
      simultaneously for 6 months, and then LAM alone was continued for 6 months. In
      the second group, LAM was started alone for the first 2 months, then INF-alpha
      added to LAM for 6 months, after which INF-alpha was stopped, and LAM alone was
      continued for 4 months. The same doses of LAM and INF-alpha were used in both
      groups. RESULTS: In the first group, the mean values of alanine aminotransferase
      (ALT) were 125 +/- 100 IU/L and 28 +/- 8 IU/L at the beginning of the treatment
      and at the end of the 12 months, respectively (P < 0.05). At the end of 6 months
      of the follow-up period, the mean ALT value was 36 +/- 37 IU/L. In group 2, mean
      ALT values were 111 +/- 63 IU/L, 35 +/- 2 IU/L and 34 +/- 2 IU/L initially, at
      the end of 12 months and at the end of 6 months of follow up, respectively (P <
      0.05). At the end of therapy, the ratios of hepatitis B early antigen (HBeAg)
      clearance and antibody to HBeAg (anti-HBe) seroconversion were 65% and 47% in
      group 1 and 60% and 40% in group 2, respectively (P > 0.05). After 6 months from
      completion of therapy, rates of seroconversion to anti-HBe were found to be 64%
      and 47% in group 1, and 53% and 46% in group 2, respectively (P > 0.05).
      Hepatitis B virus (HBV) DNA was detectable by polymerase chain reaction in only
      one patient in group 1 at the end of therapy and 6 months after termination of
      therapy. Clearance of HBV DNA in group 2 was observed in all but one patient at
      the end of the therapy. However, two patients relapsed within 6 months of
      cessation of therapy. Complete response occurred in 47% and 40% of patients at
      the end of the therapy in group 1 and 2, respectively (P > 0.05). These ratios
      were changed to 47% and 46%, respectively, 6 months after discontinuation of
      drugs (P > 0.05). CONCLUSIONS: Comparison of our two different combination
      regimens disclosed similar results in the normalization of ALT, clearance of
      HBeAg and HBV DNA and seroconversion to anti-HBe. However, the most beneficial
      combination of LAM and INF-alpha treatment modalities needs to be further
      investigated.

PMID- 12201870
TI  - Hepatitis C risk factors in Iranian volunteer blood donors: a case-control study.
AB  - BACKGROUND: In order to evaluate some possible risk factors for the spread of
      hepatitis C infection a case-control study was undertaken. METHODS: The study
      population consisted of first time blood donors referred to the Iranian Blood
      Transfusion Organization. Enzyme-linked immunosorbent assay and recombinant
      immunoblot assay anti-hepatitis C virus (HCV) tests were performed for all
      samples. Risk factors were evaluated using a questionnaire. A stepwise forward
      logistic regression analysis was used. RESULTS: The case group consisted of 193
      HCV-positive donors, and 196 HCV-negative donors comprised the control group.
      Transfusion, undergoing endoscopy, extramarital sexual activities, non
      intravenous (i.v.) drug abuse, i.v. drug abuse, and receiving wounds at war were
      found to be independent risk factors of being HCV-positive (Odds ratio: 17, 4,
      42.2, 34.4, 52.8 and 5.2, respectively). No apparent risk factors could be
      demonstrated in 24.5% of the positive cases. CONCLUSION: This study could be of
      particular interest because of the low seroprevalence of hepatitis C and the
      religious culture of the study population. There are certain medical procedures,
      lifestyle patterns, and customs and cultural matters in Iran that predispose
      people to a number of HCV risk factors.

PMID- 12201871
TI  - Fatty liver in non-alcoholic non-overweight Japanese adults: incidence and
      clinical characteristics.
AB  - BACKGROUND AND AIMS: Fatty liver is not uncommon in many countries, including
      Japan, and is mainly caused by alcohol usage and obesity. The aim of this study
      was to determine the incidence and causative factors of fatty liver in Japanese
      adults. METHODS: The clinical characteristics of 3432 Japanese adults who visited
      our hospital between January and December 2000 for thorough medical examinations
      were recorded including sex, age, body mass index (BMI), percentage body fat
      measurement using a bipedal bioimpedance instrument, history of alcohol intake,
      blood pressure, serum levels of aspartate aminotransferase, alanine
      aminotransferase (ALT), gamma-glutamyl transpeptidase, total cholesterol,
      triglyceride, uric acid, fasting blood glucose (FBG), and liver status by
      ultrasonography (USG). RESULTS: Of 3432 participants, 747 (21.8%) were diagnosed
      as having fatty liver by USG, 1873 (54.6%) were 'daily alcohol drinkers', and 698
      (20.3%) were overweight (BMI >or= 25 kg/m2). Fatty liver was more frequent in men
      and overweight subjects (P < 0.01), whereas there was no significant difference
      in the proportion of the 'daily alcohol drinker' between fatty liver and non
      fatty liver participants. The logistic regression analysis showed that BMI, ALT,
      and triglyceride were independent predictors of fatty liver in both sexes, and
      FBG, uric acid, percentage body fat, and total cholesterol were independent
      predictors of fatty liver only in men. It was noted that 319 (9.3%) were non
      alcoholic individuals with fatty liver, and 141 (4.1%) were non-alcoholic and non
      overweight individuals with fatty liver. The logistic regression analysis showed
      that percentage body fat was an independent predictor of fatty liver in non
      alcoholic and non-overweight participants in both sexes, although non-significant
      in women in the whole group. CONCLUSIONS: In our study population, 21.8% had
      fatty liver diagnosed by USG, 9.3% were non-alcoholic with fatty liver, and 4.1%
      were non-alcoholic and non-overweight with fatty liver. Our results suggest that
      central body fat distribution can correlate with the development of fatty liver,
      and that measurement of percentage body fat is useful to assess the etiology of
      fatty liver in non-alcoholic and non-overweight participants, particularly women.

PMID- 12201872
TI  - Evolution of hypoxemia in patients with severe cirrhosis.
AB  - BACKGROUND AND AIM: Hypoxemia is common in patients with cirrhosis but the
      natural history of this syndrome is unknown. The aim of this study was to follow
      a series of patients with cirrhosis and to compare patients with and without
      hypoxemia to determine their risk of complications and survival rate. METHODS:
      Fifty-eight consecutive Child-Pugh C patients with cirrhosis were included and
      followed up for 1-18 months. Blood gas measurements and plasma endothelin levels
      were measured in all patients. Blood gas measurements were repeated in 34
      patients. RESULTS: Hypoxemia was present in 35 patients (60%) (alveolar-arterial
      oxygen (AaO2) gradient > 20 mmHg) but none had pulmonary symptoms. There was no
      significant difference in liver tests and plasma endothelin levels between
      hypoxemic and non-hypoxemic patients. The occurrence of variceal bleeding and
      survival rate was not significantly different between the two groups. The AaO2
      gradient worsened in nine patients and normalized in six of the hypoxemic
      patients. The AaO2 gradient increased to more than 20 mmHg in seven non-hypoxemic
      patients. There was no relationship between AaO2 gradient changes and Child-Pugh
      score grade changes. CONCLUSION: Asymptomatic hypoxemia is common in patients
      with severe cirrhosis but it is not a predictive factor of short-term
      complications or mortality. These results should be considered when deciding on
      liver transplantation.

PMID- 12201873
TI  - Cyclooxygenase-2 mRNA is up-regulated in cirrhotic or chronic hepatitis liver
      adjacent to hepatocellular carcinoma.
AB  - BACKGROUND AND AIM: Hepatocellular carcinoma (HCC) is unique in that its
      carcinogenesis is related to inflammatory changes and regenerative activities in
      the background liver. Although there are some data on cyclooxygenase (COX)-2
      expression in HCC by immunohistochemical studies, little is known about the
      possible role of COX-2 in inducing hepatitis and/or carcinoma. To elucidate
      whether COX-2 is involved in a part of these processes, we attempted to examine
      COX-2 mRNA both in the adjacent non-tumoral liver and in HCC. METHODS: Twenty-two
      matched sets of adjacent liver and HCC specimens were analyzed for COX-2 mRNA
      expression using a real-time quantitative reverse transcription polymerase chain
      reaction. Cyclooxygenase-2 protein expression was also determined by
      immunohistochemistry. RESULTS: Cyclooxygenase-2 mRNA expression was significantly
      higher in the adjacent liver than in HCC (P = 0.016). Cyclooxygenase-2 mRNA
      expression in adjacent liver tissues was positively correlated with the modified
      histological activity index scores (r = 0.575, P = 0.006), the serum alanine
      aminotransferase levels (r = 0.536, P = 0.010), and the Ki-67 labeling indices (r
      = 0.698, P = 0.001). In contrast, COX-2 mRNA expression in HCC was not correlated
      with any of the clinicopathological features. CONCLUSIONS: Cyclooxygenase-2 is
      expressed at higher levels in the adjacent liver than in HCC, and it may be
      associated with high levels of necroinflammation and regeneration in the
      background liver. Conversely, COX-2 may have a lesser role in the progression of
      HCC.

PMID- 12201874
TI  - Gastrointestinal: Peutz-Jeghers syndrome.

PMID- 12201875
TI  - Hepatobiliary and pancreatic: a Chinese man with abdominal discomfort.

PMID- 12201876
TI  - Primary hepatic carcinoid tumor with metachronous lymph node metastasis after
      long-term follow up.
AB  - A case of hepatic carcinoid tumor occurring in a 71-year-old man is reported. The
      tumor was diagnosed initially as a hepatocellular carcinoma, and was then shown
      after resection histologically to be a carcinoid tumor. The tumor cells formed
      small nests and trabeculae separated by fibrous septa and were positive for
      Grimelius staining. Immunohistochemically, most of the tumor cells stained
      positive with chromogranin A and neuron-specific enolase. After a follow up for 5
      years and 7 months, the patient developed tumors in lymph nodes between the
      remnant liver and the lesser curvature of the stomach with no tumors in other
      organs. Histologically, the tumor cells in the lymph nodes demonstrated a pattern
      of the immunostainings consistent with carcinoid tumor. After lymphadenectomy,
      the patient is free from recurrence in the regional lymph nodes for more than 1
      year. This case is con-sidered to be a primary hepatic carcinoid tumor with
      metachronous lymph node metastasis.

PMID- 12201877
TI  - Buried bumper syndrome: old problem, new tricks.
AB  - Buried bumper syndrome is a rare complication of percutaneous endoscopic
      gastrostomy (PEG). The condition results from excessive tension between the
      external and internal bumpers. Several attributing factors may predispose the
      internal bumper to embedding in the gastric or abdominal wall. Surgical treatment
      was a reasonable approach to remove the internal bumper. The novel endoscopic
      method of exposing the buried internal bumper and subsequent removal using a
      needle knife sphincterotome has been reported. A radiological technique of
      removing the buried internal bumper was also recently described. We report two
      cases of buried soft-tip bumpers that were easily removed by external traction
      without the need for surgical, invasive endoscopic or radiological methods of
      removal. In the first case, the original tract was incompletely closed, allowing
      a new PEG tube to be inserted via the same route. In the second case, an adjacent
      site was used for the re-insertion as the original tract had completely closed.
      Both cases illustrate the ease with which the buried bumpers were removed. The
      advent of externally removable internal bumpers reduces the need for endoscopic
      or surgical removal of buried internal bumpers.

PMID- 12201879
TI  - Development of ulcerative colitis despite long-term immunosuppression with
      cyclosporin and azathioprine in an Australian Aborigine.

PMID- 12201881
TI  - Feminism and clinical nursing.

PMID- 12201882
TI  - The transition of adolescents with diabetes from the children's health care
      service into the adult health care service: a review of the literature.
AB  - Adolescents with diabetes have unique health needs, which impact upon their
      transition from children's health care services into adult health care services.
      These health needs result from the precarious period in their lives, when they
      have to cope with the stresses of being a maturing person. This coincides with
      their move from the children's into the adult health care service. Whilst coping
      with these pressures they must also keep their diabetes under control. The impact
      of emotional and physical demands upon the adolescent means that they are more
      susceptible to non-adherence, which may result in reduced diabetic control. This
      literature review identifies some of the many barriers erected to the transition
      into the adult health care system; these barriers may be constructed by any one
      of the parties involved: the children's health care team, adult health care team,
      the adolescent or their family. Principles of a successful transition are
      explored, along with the prerequisite qualities required of health care providers
      and the health care service.

PMID- 12201883
TI  - Pathogenesis of urinary tract infections: a review.
AB  - Pathogenesis of urinary tract infections (UTIs) is not well-understood. In this
      paper, we review the current understanding of UTIs, particularly in relationship
      to individuals using intermittent catheterization. Relationships exist between
      the human host, infectious agent and the environment. In the human host, the
      urethra connects the bladder to potential infectious agents on the perineum. A
      high-pressure zone exists within the urethra at a point where the urethra passes
      through the urogenital diaphragm. This zone creates a natural barrier to ascent
      of organisms colonized in the distal urethra and the bladder itself has natural
      defences against invading organisms. The interaction of host defences with
      bacteria (infectious agent) determines whether or not the bacteria persist. A
      small number of bacteria and some types of bacteria are controlled more
      effectively by natural bladder defence mechanisms and frequent bladder emptying
      than a large number of bacteria. Escherichia coli, coliforms and enterococci are
      considered common bacterial causes of UTIs and are found in high numbers on the
      perineum. Intermittent catheterization is an effective way of bladder emptying
      but as an invasive procedure it remains a risk factor in the development of UTI.

PMID- 12201884
TI  - Psycho-affective disorder in intensive care units: a review.
AB  - This paper reviews the literature related to the Intensive Care Unit (ICU)
      Syndrome. The intention of the paper is to explore the range of psychotic and
      affective phenomena that may be observed in practice, together with the
      management of contributory stressors. Patients experience a range of psycho
      affective disturbances that may be triggered by drugs, the environment,
      dehumanizing practices and sleep deprivation. Symptoms do not always disappear
      following discharge and further research is required to determine the long-term
      psychological effects of an ICU. Comprehensive assessment of the patient's
      psychological state, using an appropriate tool, is necessary and should form an
      integral part of ongoing care. Interventions identified include eradication of
      dehumanizing behaviour, modification of environmental stimuli, effective
      communication and therapeutic touch. Where possible, communication needs should
      be addressed prior to admission, and patients and their families prepared for the
      unfamiliar world of the ICU.

PMID- 12201885
TI  - Need for appropriate written information for patients, with particular reference
      to head and neck cancer.
AB  - Patients need and want written information. There is evidence that giving
      comprehensible information increases overall satisfaction with the care given by
      healthcare professionals. This paper provides a review of the literature on
      patients' need for appropriate information, with particular reference to head and
      neck cancer, based on searches of electronic databases. Head and neck cancers are
      among the least common cancers in the UK but these patients have very specific
      and great needs. Written information is a cost-effective intervention that
      complements verbal advice given by healthcare professionals. Evidence suggests
      that patient information leaflets are poor and are in language that is difficult
      for the public to understand. Considerable time, effort and user involvement are
      required to produce acceptable and appropriate information leaflets for patients.

PMID- 12201886
TI  - A qualitative study of coping in the early stage of acute traumatic hand injury.
AB  - Twenty patients with acute traumatic hand injury were interviewed 8-20 days after
      the day of the accident. The aim of the study was to identify coping strategies,
      defined as thoughts or actions used by the hand-injured patients to manage stress
      factors and resulting emotions in the early stage. Stress factors were reported
      in an earlier study. The analyses of the interviews followed the first steps in
      the analytical process described in a modified model of grounded theory. Eleven
      different coping strategies were identified in the interviews. By "comparing with
      something worse", "positive thinking", "relying on personal capacity",
      "distancing" and "distracting attention" the patients tried to play down the
      seriousness of the problem or situation. Other coping strategies used by the hand
      injured were "accepting the situation", "seeking social support", "maintaining
      control", "solving practical problems by oneself", "pain-relieving actions" and
      "active processing of the trauma experience." The findings of the study show how
      important it is to identify the patient's own way of coping with a stressful
      illness situation in order to give adequate psychosocial support.

PMID- 12201887
TI  - Older people seeking solutions to constipation: the laxative mire.
AB  - This article reports an extensive descriptive survey of 90 older people (65+
      years) living in the community who sought through in-depth, semistructured
      interviews to explore their experiences and responses to constipation. The
      composite story of these older people is that seeking a solution to constipation
      may be fraught with great difficulty. Most commonly tried are laxatives, yet
      laxative use can be like a mire. The older people tend to be uncertain of which
      way to turn to avoid getting stuck in a murky conglomeration of laxative options.
      The imperative for self-management of constipation is strong amongst most of the
      older people and the process in which they engage when seeking for a solution is
      discussed. There is an evident frustrating lack of readily identifiable and
      accessible services and information that could help them navigate successfully
      through or around this mire. "Through the mire" would be the appropriate use of
      suitable laxatives with minimal side-effects. "Around the mire" would be the
      gaining of useful solutions other than laxative use. Solutions may be strategies
      to prevent constipation or to treat constipation. The needs of these older people
      seeking solutions to constipation are grouped into two main categories: provision
      of accessible, empathetic and useful advice about affordable solution choices,
      and accessibility to solutions, including laxatives, where evidence-based
      knowledge informs selection or prescription of the solution. Eight major
      recommendations, including research suggestions, are offered for consideration.

PMID- 12201888
TI  - "The Hidden Client"--women caring for husbands with COPD: their experience of
      quality of life.
AB  - The purpose of this phenomenological study was to describe the experience of
      quality of life of women, taking care of husbands with chronic obstructive
      pulmonary disease (COPD). Unstructured, in-depth, tape-recorded personal
      interviews were used to collect data from six women living with husbands with
      COPD. The women ranged from 47 to 69 years in age and their husbands had given up
      work because of the illness. The wives in the study were dissatisfied with their
      lack of recreation, as well as support from friends, families and health care
      providers. Factors that increased the wife's quality of life were children and
      grandchildren and being able to please the husband and care for him until the
      very end.

PMID- 12201889
TI  - Social support and its relation to fear and anxiety in patients awaiting coronary
      artery bypass grafting.
AB  - The purpose of this study was to ascertain social support resources available for
      patients awaiting coronary artery bypass grafting (CABG) and the effect of social
      support on their fear and anxiety. A postal questionnaire was sent to 270
      patients awaiting CABG in one hospital, 207 of whom responded. Norbeck's Social
      Support Questionnaire (NSSQ) was used. The quality of basic cardiac information
      (QBCI) and the social support wanted (WSS) by patients were measured with an
      instrument developed for this study. Fear was measured with the Bypass Grafting
      Fear Scale (BGFS) developed for this study. Anxiety was measured with
      Spielberger's State-Trait Anxiety Inventory (STAI). The results were analysed
      using frequency and percentage distributions, cross-tabulation, non-parametric
      tests and logistic regression. Heart patients' spouses provided the most
      emotional and tangible aid. Low emotional support from the social network was
      associated with high anxiety. Half the patients rated the quality of basic
      information as good or excellent. Those who perceived the quality of information
      to be excellent experienced mild fear. Those who displayed high fear wanted
      informational support from nurses more often than patients with lower fear. We
      conclude that the fear and anxiety of patients awaiting CABG are connected with
      their social support resources.

PMID- 12201890
TI  - Patients' learning needs after hip arthroplasty.
AB  - The purpose of this study was to describe patients' learning needs after hip
      arthroplasty and compare them prior to and 2 weeks after hospital discharge. Data
      were collected in two phases from 22 surgical wards in 17 hospitals in Finland
      using a Canadian Patient Learning Needs Scale (Galloway et al., 1996). The first
      questionnaire (n=212, 81%) was completed before hospital discharge and the second
      (n=144, 55%) was completed at home after hospital discharge. Results indicated
      that patients' learning needs diminished significantly after hospital discharge.
      In both questionnaires patients felt that the most important information was
      about complications and symptoms. Information about medication was ranked the
      second most important. Demographic variables such as age, gender, education and
      working life were clearly related to learning needs. Women over 60 years old, and
      less educated and retired respondents had many learning needs.

PMID- 12201891
TI  - An empowerment approach to needs assessment in health visiting practice.
AB  - This paper examines the usefulness of an integrated approach to needs assessment
      using an empowerment framework, within a health visitor/client interaction, in
      the home setting. It is intended to demonstrate the existence of a flexible
      approach to assessing need that is based on research about necessary processes
      for carrying out health visiting. The design of the tool described in this paper
      allows the use of professional judgement as well as fulfilling commissioning
      requirements to address health outcomes. Health promotion and empowerment are
      central to health visiting practice and should be reflected in the way needs are
      assessed. Many NHS trusts have introduced a system of targeting and prioritizing
      health visiting through a system of questioning to assess needs. This may reveal
      the work that health visitors do, but may also inhibit the open, listening
      approach required for client empowerment. Different methods of assessing need can
      be used that do not compromise the commissioning requirements, the health
      visitor's duty of care or professional accountability. The empowerment approach
      is key to the philosophy of health visiting. There are ways of approaching needs
      assessment that do not compromise the ethos of partnership-working in a health
      promoting way.

PMID- 12201892
TI  - Intermittent versus indwelling catheters for older patients with hip fractures.
AB  - Nursing staff identified postoperative urinary tract infection (UTI) in patients
      with hip fracture as an increasing problem. A quality improvement project was
      carried out to investigate the problem and to reduce the incidence. The aim of
      the study was to describe the occurrence of UTI among patients with hip fracture
      before and after surgery, to assess whether the decision to use intermittent
      catheters instead of indwelling catheters was adopted and to test the hypothesis
      that hospital stay is significantly longer for patients with UTI than for those
      without infection. One hundred and forty-four patients were investigated for
      bacteriuria before the first catheterization and 1 week after the last
      catheterization. Positive urine cultures on admission to hospital were found in
      38% of patients. Among those free from bacteria on admission, 61% had a positive
      urine culture after indwelling catheterization compared with 32% in the group
      treated with intermittent catetherization. A significantly longer hospital stay
      (P </= 0.05) was found among patients with UTI. The reason for using an
      indwelling catheter was not found in any medical or nursing documentation for 29%
      of the patients. The study points to the necessity for systematic assessment to
      detect and prevent UTI among older patients with hip fracture.

PMID- 12201893
TI  - Mental health nurses: changing practice?
AB  - Project 2000 envisaged that the nurse practitioner of the future should act as an
      "agent for change", using research evidence to address those aspects of practice
      deemed detrimental to patient care. A Department of Health funded study
      investigating the careers of nurse diplomates provides information on the extent
      to which newly qualified nurses were able to change aspects of practice, what
      factors inhibited changes and which personnel played a key role in facilitating
      change. Key factors which inhibited newly qualified nurses acting as change
      agents were lack of experience and confidence, as well as attitudes of other
      members of staff. Staff of a higher grade, immediate line managers and healthcare
      assistants all played a key role in facilitating change.

PMID- 12201894
TI  - Cultural conflict: the impact of western feminism(s) on nurses caring for women
      of non-English speaking background.
AB  - Much research has been conducted for understanding the health needs of people of
      different cultural backgrounds and the problems they experience in seeking health
      care. In Australia, despite such research, it is argued that there remains an
      exclusionary health care culture that continues to affect equity and access for
      people of non-English speaking background. There was a need for research in which
      health professionals examined their own Anglo-Australian culture and its impact
      on other ethnic communities. Such concerns provided the impetus for a feminist
      praxis study to engage nurses in understanding and improving care for migrant
      women. This study was conducted with 26 nurses in a paediatric hospital in
      Melbourne, Australia. Five collaborative research groups were formed, each
      consisting of four to six nurses who were co-researchers. Together, the nurses
      and researchers explored the health care experiences of migrant women, using a
      variety of quantitative and qualitative data collection strategies. This paper
      explores a major finding of the study, which was the impact of liberal feminist
      approaches on the practices of Australian nurses who cared for women of different
      ethnicity and race. The study found that the efforts of liberal feminist nurses
      to "treat all people the same" meant that women from different cultural
      backgrounds did not always receive equity in care. Through the feminist praxis
      process the nurses were able to explore contradictions in their practice and
      focus on equity in care to meet the specific gendered and racially constructed
      needs of women of different cultural backgrounds. A number of strategies were
      adopted that included regular use of female health interpreters and provision of
      privacy for migrant women when caring for their children.

PMID- 12201895
TI  - A comprehensive definition of infant colic: parents' and nurses' perspectives.
AB  - Colic is a term that is often used for crying in infancy. There is no unified
      definition, the aetiology is disputed and there is no effective method of
      treatment. Therefore, the crying infant constitutes a problem for parents and for
      nurses in child health clinics. The purpose of the study was to develop a
      clinically acceptable framework for describing colic. The design is exploratory,
      and data were collected through qualitative in-depth interviews with nurses and
      parents of crying babies. The infants identified by parents and nurses had
      periods of crying or fussing for more than 3 hours a day, the crying occurring on
      more than 3 days in any 1 week and lasting for more than 3 weeks. Three
      categories of crying emerged (intense crying, non-specific fussing and crying,
      feeding-related crying) that presumably differ in aetiology. An overall
      definition of colic is proposed that incorporates these categories. The proposed
      definition may function as a diagnostic tool for nurses when they encounter
      problems of infant crying. The definition provides nurses with clinical criteria
      that can guide data collection. More specific assessment and categorization of
      infant crying will be helpful for nurses in addressing problems of colic.

PMID- 12201896
TI  - Development of a short form of the Quality from the Patient's Perspective (QPP)
      questionnaire.
AB  - Patients' views on the quality of care are important and it is desirable that
      these can be assessed using short, yet valid and reliable instruments. The aim of
      the work reported here was to develop and test a short version of an established
      questionnaire: Quality from the Patient's Perspective (QPP). Patients (n=162, 79%
      response rate) receiving care at medical and surgical departments in two Swedish
      hospitals responded to the original QPP as well as to a newly developed short
      version. An ethical research committee approved the study. Pearson correlations
      were computed between the long and short forms and differences between means were
      analysed with t-tests. Reliability was estimated by computing Cronbach alpha
      coefficients. Correlations of acceptable size were found between the short form
      and the original QPP. The short form also had acceptable reliability
      coefficients. The strengths of the work are that the items in the short version
      are derived from a patient perspective and are formulated in words used by
      patients; the items still have a theoretical foundation, which makes the
      interpretation of results more meaningful; global formulations such as "What do
      you think about your care?" have been avoided; the short format should make the
      questionnaire more attractive for many patients to respond to. Limitations are
      that results indicate that the short form does not fully measure what the long
      form does. Therefore, when the short form is used in practice, a two-step
      procedure is suggested, where a follow-up is done with a selection of items from
      the original long form. This selection could be restricted to areas where
      problems may be suspected, based on the results from the short form.

PMID- 12201897
TI  - Estimation of energy intake in clinical practice: a comparison between a food
      record protocol and a precoded food record book.
AB  - The aim of this study was to compare energy intake estimated from a clinical food
      record protocol (CFRP) with that from a precoded food record book (PFRB) as
      reference method. Food and fluid consumption were recorded in 10 older patients
      using a CFRP in parallel with a PFRB during a 6-day period. The results showed
      that there were no significant differences in mean energy intake estimated from
      the CFRP as compared with that estimated from the PFRB. The correlation
      coefficient between the calculated daily energy intake from the CFRP and PFRB was
      0.96. The differences in energy intake (kcal/day) between the CFRP and PFRB,
      plotted against their mean value for 10 patients, showed that results were within
      the limits of agreement (mean +/- 2SD) for nine patients. The differences in each
      day's energy intake between the two methods plotted against their mean value
      showed that 97% of the estimated daily energy intake was within the limits of
      agreement. The weighted kappa between the two methods was 0.76. The CFRP would
      seem to be acceptable for the estimation of mean energy intake in the hospital
      setting.

PMID- 12201898
TI  - Educational needs of families caring for patients with schizophrenia.

PMID- 12201899
TI  - Heterogeneity missing.

PMID- 12201901
TI  - Specific immunotherapy in Albanian patients with anaphylaxis to hymenoptera
      venoms.
AB  - BACKGROUND: Severe allergic reactions during rush-specific immunotherapy (Rush
      SIT) may occur in the treatment of hymenoptera sting allergy. The objective of
      the present study was to examine the characteristics of allergic reactions during
      Rush-SIT in a cohort of patients with allergy towards hymenoptera venom in the
      mediterranean population of Albania. METHODS: A retrospective study was performed
      using the clinical reports of 37 patients with venom of bee (apinae), wasp
      (vespidae, subfamily vespinae) or paperwasp (vespidae, subfamily polistinae)
      allergy treated with Rush-SIT between 1987 and 1996. After hymenoptera sting
      allergy diagnosis according to anamnesis and intracutaneous tests the patient
      were treated with Rush-SIT. The protocol lasted 3 - 4 d with an increase in the
      concentration from 0.01 microg/ml to 100 microg/ml. Anaphylactic reactions were
      classified according to the Mueller-classification. RESULTS: The frequency of
      reactions during Rush-SIT for bee-venom was 4.7% and for wasp-venom was 1.5% (p <
      0.01). The mean frequency of reactions of Mueller grade II for the bee-venom Rush
      SIT patients during the first 4 d (= 26 injections) was 0.73 and for the wasp
      venom Rush-SIT patients 0.15. No patient experienced a third-degree reaction.
      94.6% of the patient supported an end dose of 100 microg. CONCLUSIONS: Rush-SIT
      is a reliable method for the treatment of anaphylactic reactions to hymenoptera
      venom even in less developed countries. Bee-venom Rush-SIT was found to cause
      higher numbers allergic reactions than wasp or paperwasp Rush-SIT.

PMID- 12201902
TI  - Problems in early diagnosis of bladder cancer in a spinal cord injury patient:
      report of a case of simultaneous production of granulocyte colony stimulating
      factor and parathyroid hormone-related protein by squamous cell carcinoma of
      urinary bladder.
AB  - BACKGROUND: Typical symptoms and signs of a clinical condition may be absent in
      spinal cord injury (SCI) patients. CASE PRESENTATION: A male with paraplegia was
      passing urine through penile sheath for 35 years, when he developed urinary
      infections. There was no history of haematuria. Intravenous urography showed
      bilateral hydronephrosis. The significance of abnormal outline of bladder was not
      appreciated. As there was large residual urine, he was advised intermittent
      catheterisation. Serum urea: 3.5 mmol/L; creatinine: 77 umol/L. A year later,
      serum urea: 36.8 mmol/l; creatinine: 632 umol/l; white cell count: 22.2;
      neutrophils: 18.88. Ultrasound: bilateral hydronephrosis. Bilateral nephrostomy
      was performed. Subsequently, blood tests showed: Urea: 14.2 mmol/l; Creatinine:
      251 umol/l; Adjusted Calcium: 3.28 mmol/l; Parathyroid hormone: < 0.7 pmol/l (1.1
      - 6.9); Parathyroid hormone-related protein (PTHrP): 2.3 pmol/l (0.7 - 1.8).
      Ultrasound scan of urinary bladder showed mixed echogenicity, which was diagnosed
      as debris. CT of pelvis was interpreted as vesical abscess. Urine cytology:
      Transitional cells showing mild atypia. Bladder biopsy: Inflamed mucosa lined by
      normal urothelial cells. A repeat ultrasound scan demonstrated a tumour arising
      from right lateral wall; biopsy revealed squamous cell carcinoma. In view of
      persistently high white cell count and high calcium level, immunohistochemistry
      for G-CSF and PTHrP was performed. Dense staining of tumour cells for G-CSF and
      faintly positive staining for C-terminal PTHrP were observed. This patient
      expired about five months later. CONCLUSION: This case demonstrates how delay in
      diagnosis of bladder cancer could occur in a SCI patient due to absence of
      characteristic symptoms and signs.

PMID- 12201903
TI  - Survey of the knowledge, attitude and practice of Nigerian surgery trainees to
      HIV-infected persons and AIDS patients.
AB  - BACKGROUND: The incidence of HIV infection and AIDS is rising in Nigeria.
      Surgeons are at risk of occupationally acquired infection as a result of intimate
      contact with the blood and body fluids of patients. This study set out to
      determine the knowledge, attitude and risk perception of Nigerian surgery
      residents to HIV infection and AIDS. METHODS: A self-administered postal
      questionnaire was sent to all surgery trainees in Nigeria in 1997. RESULTS:
      Parenteral exposure to patients' blood was reported as occurring 92.5% times, and
      most respondents assessed their risk of becoming infected with HIV as being
      moderate at 1-5%. The majority of the respondents were not aware of the CDC
      guidelines on universal precautions against blood-borne pathogens. Most support a
      policy of routinely testing all surgical patients for HIV infection but 76.8%
      work in centers where there is no policy on parenteral exposure to patients'
      blood and body fluids. Most (85.6%) do not routinely use all the protective
      measures advocated for the reduction of transmission of blood borne pathogens
      during surgery, with the majority ascribing this to non-availability. Most want
      surgeons to be the primary formulators of policy on HIV and surgery while not
      completely excluding other stakeholders. CONCLUSIONS: The study demonstrates the
      level of knowledge, attitude and practice of Nigerian surgery trainees in 1997
      and the need for policy guidelines to manage all aspects of the healthcare worker
      (HCW), patients, and HIV/AIDS interaction.

PMID- 12201904
TI  - Position paper on therapeutic drug monitoring of antiretroviral agents.
AB  - Monitoring drug concentrations in humans to optimize efficacy and reduce toxicity
      is not a new concept in clinical pharmacology. It has been successfully applied
      to many different classes of drugs. As a result of considerable concentration and
      response data, the concept of therapeutic drug monitoring (TDM) has been expanded
      to certain antiretroviral compounds. In particular, protease inhibitors and
      nonnucleoside reverse transcriptase inhibitors may be viable candidates for TDM,
      and limited clinical trial data suggest monitoring plasma concentrations of these
      agents may indeed clinically benefit patients with HIV infection. A primary
      distinction between TDM of antiretroviral drugs compared with other drugs is that
      multiple agents are concomitantly used to treat HIV infection. As with all
      illnesses that require self-administered drug therapy, poor adherence is a major
      impediment to success. However, in the treatment of HIV infection, inadequate
      drug concentrations will result in the appearance or evolution of drug resistance
      mutations that can endanger present and future drug treatment options. Procedures
      for sample collection, cross-validation of analytical procedures, and
      interpretation of assay results should be standardized. More clinical data are
      needed to confirm this approach and methods of implementing TDM should be further
      explored. This position paper offers guidelines to aid clinicians who choose to
      incorporate TDM into the routine care of their patients.

PMID- 12201905
TI  - Cross-resistance among nonnucleoside reverse transcriptase inhibitors limits
      recycling efavirenz after nevirapine failure.
AB  - Heterogeneity in genotype mutations associated with resistance of HIV to
      nonnucleoside reverse transcriptase inhibitors (NNRTIs) should allow
      identification of patients failing nevirapine (NVP) who might benefit from
      efavirenz (EFV)-containing salvage regimens. To establish the feasibility of
      recycling EFV after failure of NVP-containing regimens genotypic data on 103 NVP
      failed patients were analyzed to evaluate the prevalence of EFV resistance
      conferring mutations. A clinically significant resistance to EFV was found in 50
      of 103 (58%) of NVP-failed subjects. Furthermore, the 3-month virological
      response to salvage regimens containing EFV was assessed in patients previously
      treated with NVP and carrying single mutations conferring resistance to this
      drug. A proportion of HIV RNA less than 500 copies/ml at 3 months was obtained
      only in 2 of 12 (17%) of EFV-treated subjects compared with 35 of 67 (52%) of
      those without NNRTI mutations (OR, 0.18; 95% CI, 0.03-0.79). The median HIV-1 RNA
      decrease after 3 months was -0.63 log(10) among patients carrying single NNRTI
      associated mutations compared with -1.32 log(10) among those without any NNRTI
      mutations. No virological response was observed in six patients harboring a
      single Y181C/I mutation. On the basis of the present data, sequential use of
      NNRTIs should be avoided in the management of treatment failure.

PMID- 12201906
TI  - Role of placental cytokines in transcriptional modulation of HIV type 1 in the
      isolated villous trophoblast.
AB  - During pregnancy, a complex cytokine network is present at the maternal-fetal
      interface in order to support normal growth and development of the placenta and
      fetus. HIV can frequently infect placental trophoblast but the impact of
      cytokines produced locally by the placenta and decidua on virus expression and
      replication is unknown. We comprehensively assayed the cytokines typically
      present in the placental microenvironment for their potential to modulate HIV
      transcriptional activation in the isolated trophoblast cells employing a
      transient transfection assay with luciferase as a reporter gene. Long terminal
      repeats (LTRs) of two divergent virus strains, HIV-1 LAI and HIV-1 NDK, were used
      to analyze virus-specific features. Four cytokines, epidermal growth factor
      (EGF), granulocyte-macrophage colony-stimulating factor (GM-CSF), interleukin 1
      beta (IL-1 beta), and tumor necrosis factor alpha (TNF-alpha), were found to
      stimulate promoters of both viruses, whereas interferon alpha (IFN-alpha) and IFN
      beta were found to suppress the transcription driven from both promoters. The
      differences observed between the two viruses did not reach a statistically
      significant level. None of the remaining cytokines, including EGF; GM-CSF;
      insulin-like growth factor I (IGF-I); IFN-alpha, IFN-beta, and IFN-gamma; IL-1
      alpha, IL-1 beta, IL-2, IL-6, and IL-10; leukemia inhibitory factor (LIF);
      macrophage colony-stimulating factor (M-CSF); platelet-derived growth factor BB
      (PDGF-BB); transforming growth factor beta (TGF-beta); and TNF-alpha, affected
      transcriptional expression of the promoter constructs. Our results demonstrate
      that the local balance of cytokines may be critical for activation of HIV in the
      syncytiotrophoblast-cytotrophoblast layer and thus play an important role in the
      transmission of virus across the placental barrier.

PMID- 12201907
TI  - Identification of two CRF11-cpx genomes and two preliminary representatives of a
      new circulating recombinant form (CRF13-cpx) of HIV type 1 in Cameroon.
AB  - Recombination is an efficient mechanism of HIV-1 to generate genetic variability.
      Some of the recombinant forms of HIV-1 that have been described are of epidemic
      importance, and they are referred to as circulating recombinant forms (CRFs). In
      this study, we characterized four HIV-1 isolates from Cameroon that had
      previously been classified as subtype J in the protease gene and as subtype A in
      the env C2-V5 region. Analyses of the nearly complete genomes revealed that two
      of the samples (95CM-1816 and 96CM-4496) had the same recombinant structure as
      CRF11-cpx. The two remaining samples (96CM-1849 and 96CM-4164) constituted a new
      recombinant virus variant with genomic regions identified as subtypes A, G, J,
      and CRF01-AE. This mosaic virus structure was found in two individuals who had no
      direct epidemiological relationship, and may thus represent a new CRF. The
      fragments that were classified as subtype J in the new recombinant form were more
      related to subtype J regions of the CRF11-cpx sequences than to the reference
      strains of subtype J. The complex structures of CRF11-cpx and our new recombinant
      form, which are both the result of at least four recombination events, exemplify
      the coming difficulties in characterizing the internal relationships and origins
      of future recombinant HIV-1 strains. The new recombinant structure has been
      designated CRF13-cpx in the Los Alamos HIV Sequence Database.

PMID- 12201908
TI  - Prevalence of G333D/E in naive and pretreated HIV-infected patients.
AB  - A substitution at codon 333 (G -->D/E) within the reverse transcriptase (RT) gene
      causes resistance to both zidovudine (AZT) and lamivudine (3TC) in a background
      of mutations associated with loss of sensitivity to both drugs. In the absence of
      G333D/E, M184V restores the sensitivity to AZT in viruses harboring AZT-resistant
      genotypes. In this study, we examined the prevalence of the G333D/E mutation in
      plasma samples from 401 HIV-infected individuals from a routine clinical
      practice. Genotypic results could be obtained in 277 (81%) specimens belonging to
      pretreated subjects and in all 65 samples from treatment-naive individuals. The
      overall prevalence of the G333D/E mutation was 13.2%, without significant
      differences when comparing naive (10.8%) and treatment-experienced patients
      (13.7%). The codon 333 mutation was associated with AZT/3TC-resistant genotypes
      in 76.3% of pretreated individuals but in none of the treatment-naive
      individuals. In conclusion, the G333D/E mutation must be considered a natural
      polymorphism, which appears in 11% of treatment-naive HIV-infected individuals.
      In AZT-experienced patients, it might be advisable to exclude its presence before
      adding 3TC in combination in the hope of obtaining a restoration of AZT
      sensitivity if M184V develops.

PMID- 12201909
TI  - A transmissible human endogenous retrovirus.
AB  - The transmissibility of the human endogenous retrovirus HERV-H/RGH-2 was
      investigated by marker rescue: intraspecies transmission of HERV-H/RGH-2
      retrovirus particles was attempted by cocultivation of virion-producing, long
      term cell cultures spontaneously formed from peripheral blood mononuclear cells
      from several multiple sclerosis patient cultures with a retroviral vector
      construct-harboring cell line. Transmissibility was assessed by assays for
      productive infection (reverse transcriptase activity), and assays for rescue of
      the retroviral vector construct in indicator cells. Our studies show that the
      human endogenous retrovirus HERV-H/RGH-2 is transmissible, albeit at a very low
      level. The human endogenous retrovirus HERV-H/RGH-2 is associated with multiple
      sclerosis (MS). Previously, we demonstrated sequence variants of the human
      endogenous retrovirus HERV-H family in virion form, by applying RT-PCR to virion
      RNA from the supernatants of long-term MS cell cultures, and to the particulate
      fraction of a series of MS patient plasma samples.

PMID- 12201910
TI  - RNA secondary structure and squence conservation in C1 region of human
      immunodeficiency virus type 1 env gene.
AB  - We have analyzed amino acid, nucleotide sequence, and RNA secondary structure
      variability in the env gene of human immunodeficiency virus type (HIV-1). In
      applying algorithms for computing optimal RNA-folding patterns to a nonredundant
      data set of 178 env nucleotide sequences, we found a conserved RNA stem-loop
      structure in the first conserved (C1) region of the env gene. This detailed
      examination also revealed the known secondary structure conservation of the Rev
      responsive element (RRE). This finding is also supported by a higher third
      position conservation of the translatable reading frame along these subregions.
      The typical folding of the C1 region consists of two isolated stem-loop
      structures. These highly conserved structures are likely to have a biological
      function. This assumption is supported by the conservation of the third position
      along the coding region of these structures. The third position retains a
      conservation level above what would be statistically expected.

PMID- 12201911
TI  - Full-length genome analysis of HIV-1 subtype C utilizing CXCR4 and intersubtype
      recombinants isolated in South Africa.
AB  - The HIV-1 epidemic in South Africa is largely due to subtype C viruses, which
      preferentially use CCR5 as a coreceptor for infection. We describe full-length
      genome sequences of two CXCR4-utilizing HIV-1 subtype C viruses and two
      intersubtype recombinants from South Africa. Three of the viruses (99ZACM4,
      99ZACM9, and 99ZASW7) were isolated in 1999 from AIDS patients in Johannesburg,
      and a fourth virus (98ZADu178) was isolated in Durban in 1998 from an
      asymptomatic female sex worker. Isolates 99ZASW7 and 99ZACM9 from Johannesburg
      were subtype C throughout the genome, 99ZASW7 used the CXCR4 coreceptor, and
      99ZACM9 used both CCR5 and CXCR4. Isolate 98ZADu178 from Durban was a novel
      recombinant between subsubtype A2 and subtype C. The third isolate from
      Johannesburg, 99ZACM4, was a complex, novel recombinant with multiple breakpoints
      and contained segments of subtypes A, C, D, G, and K. These results establish the
      presence of intersubtype recombinants in South Africa, indicating that ongoing
      surveillance for other subtypes and recombinants is necessary.

PMID- 12201912
TI  - Envelope sequence variation and phylogenetic relations of human T cell
      lymphotropic virus type 1 from endemic areas of Colombia.
AB  - The HTLV-1 envelope gene of 12 TSP/HAM patients from two endemic areas of
      southwest Colombia (Tumaco and Buenaventura) was amplified by nested PCR,
      sequenced, and compared with previously reported HTLV-1 envelope sequences from
      isolates worldwide. In general, the sequence divergences among all Colombian
      samples ranged from 0.1 to 1.6%. Some amino acid substitutions, referring to the
      ATK-1 prototype strain in the surface domain gp46 and in p21, were highly
      prevalent in southwest Colombia, suggesting a geographical clustering of
      mutations in the envelope gene. The phylogenetic analysis showed that the
      Colombian isolates belong to the HTLV-1a lineage with minor subgroups. The
      genetic distance between Colombian and Japanese isolates ranged from 0.1 to 1.8%;
      in comparison, the genetic distance between Colombian and Caribbean isolates
      ranged from 0.4 to 2.2%. Our results strongly suggest that the actual
      quasispecies populations in southwest Colombia have been generated by separate,
      differently timed introductions of virus.

PMID- 12201913
TI  - Simultaneous introduction of HIV type 1 subtype A and B viruses into injecting
      drug users in southern Ukraine at the beginning of the epidemic in the former
      Soviet Union.
AB  - The vast majority of HIV-1 strains from the epidemic in the former Soviet Union
      (FSU) belong to subtype A (IDU-A) and CRF03_AB (IDU-A/B), for which IDU-A is one
      of parental strains; no epidemic by another parental virus, belonging to subtype
      B (IDU-B), has yet been identified. To characterize viruses present during the
      early stage of the epidemic in southern Ukraine, where the first outbreaks in the
      FSU were registered, we obtained partial env and pol sequences from IDUs from
      Odessa and Nikolaev and compared them with viruses from other outbreaks. All
      viruses from Odessa belonged to the IDU-A type, which is in accord with previous
      studies. At the same time, we found that the outbreak in Nikolaev was caused by
      IDU-B viruses, indicating that this outbreak is the result of an independent
      virus introduction. Phylogenetic analysis of viruses from the FSU supported the
      epidemiological data suggesting that the HIV-1 epidemic in the FSU started in
      southern Ukraine.

PMID- 12201915
TI  - Antenatally detected, unilateral dilatation of the renal pelvis: a critical
      review. 1. Postnatal non-operative treatment 20 years on--is it safe?
AB  - BACKGROUND: Non-operative postnatal treatment of antenatally detected
      hydronephrosis, consistent with pyelo-ureteral obstruction, has functioned well
      during follow-ups of up to 17 years. However, doubts are still expressed and,
      admittedly, the final verdict on this new policy is still remote. The purpose of
      this review is to define the state of art and to serve as a background for future
      randomized clinical trials, which still are missing. METHODS AND MATERIAL: From
      the literature, 6 patient series were chosen based on the following criteria:
      publication during the 1990s to allow for a longer follow-up and better
      diagnostic tools; consecutive patient series; and compliance with a 50-point
      form. Data, from 593 kidneys, were then pooled. Result of the compilation: Four
      hundred and seventy-four kidneys, with differential function >40%, were allocated
      to expectancy and followed for 2-144 (mean 23) months. Four hundred and twenty
      five (90%) were successful, independent of presence of caliectasis. Forty-nine
      (10%) had delayed pyeloplasty, after which declined function mostly improved /
      normalized - similar to 108 kidneys with early pyeloplasty because of an initial
      differential function <40%. Hydronephrotic size and isotope wash out rate did not
      predict outcome. CONCLUSIONS: These figures agree with other reports: few cross
      overs and functional recovery also after delayed operations. Thus, so far, with a
      caveat for future deterioration, expectancy seems safe and promising, in
      unilateral and probably in bilateral cases with normal function, although perhaps
      not in solitary kidneys. Hopefully, this review, together with a forthcoming
      communication on long-term risks and urgent research needs, will help to design
      future randomized clinical trials.

PMID- 12201916
TI  - Antenatally detected, unilateral dilatation of the renal pelvis: a critical
      review. 2. postnatal non-operative treatment--long-term hazards, urgent research.
AB  - BACKGROUND: Even after two decades, there is still much discussion about the
      postnatal treatment of antenatally detected, isolated pelvic dilatation
      (consistent with pyelo-ureteral junction obstruction). A recent review concluded
      that non-operative expectancy seemed safe - even after 17 years in certain cases.
      However, the final outcome, i.e. when these children have reached old age, is
      remote. OBJECTIVE: This review takes stock of conceivable long-term hazards and
      evaluates prognosticating tools, and offers a basis for protocols for future
      randomized controlled trials. Long-term hazards: Symptoms in this context are
      generally considered ominous. In the antenatally detected cases, i.e. primarily
      asymptomatic, symptoms have been reported but they were not necessarily combined
      with renal damage. Hydronephroses, so mild, that they are written off, may
      deteriorate later on (indeed insidiously), although probably seldom. Urgent
      research: A predictor of outcome is eagerly pursued but hard to obtain, due to
      the difficulty in defining true obstruction in compliant systems such as the
      urinary one. Ordinary diagnostics offer no help, but there are promising
      innovations: constant pressure/flow assessment (flow necessary to keep a preset
      intrapelvic pressure), NAG/creatinine in pelvic urine, and TGFbeta-1 in voided
      urine. Renal microstructure, sometimes severely damaged early (which disagrees
      with the good results with expectancies) could possibly herald future
      deterioration. CONCLUSION: Adverse developments should be meticulously documented
      and published swiftly, so policy can be changed if necessary, before it is too
      late. Cognizance of their existence, not necessarily frequency and statistics, is
      then first order. Efforts to design prognosticating tools has also high priority.

PMID- 12201917
TI  - The role of pelvic-floor therapy in the treatment of lower urinary tract
      dysfunctions in children.
AB  - The pelvic-floor is under voluntary control and plays an important role in the
      pathophysiology of lower urinary tract (LUT) dysfunctions in children, especially
      of non-neuropathic bladder sphincter dysfunction. The following therapeutic
      measures can be applied to try to influence the activity of the pelvic-floor
      during voiding: proprioceptive exercises of the pelvic-floor (manual testing),
      visualization of the electromyographic registration of relaxation and contraction
      of the pelvic-floor by a curve on a display (relaxation biofeedback), observation
      of the flow curve during voiding (uroflow biofeedback), learning of an adequate
      toilet posture in order to reach an optimal relaxation of the pelvic-floor, an
      individually adapted voiding and drinking schedule to teach the child to deal
      consciously with the bladder and its function and a number of simple rules for
      application at home to increase the involvement and motivation of the child. In
      children however with persisting idiopathic detrusor instability additional
      therapeutic measures may be necessary to improve present urologic symptoms
      (incontinence problems, frequency, urge) and to increase bladder capacity.
      Intravesical biofeedback has been used to stretch the bladder and seems to be
      useful in case of sensory urge. Recently a less invasive technique, called
      transcutaneous electrical nerve stimulation (TENS), has been applied on level of
      S3 with promising results in children with urodynamicaly proven detrusor
      instability, in which previous therapies have failed.

PMID- 12201918
TI  - Alarm treatment for childhood nocturnal enuresis: an investigation of within
      treatment variables.
AB  - OBJECTIVE: The enuresis alarm has been widely advocated as an effective
      intervention in the treatment of childhood nocturnal enuresis. Although there is
      a body of evidence concerning which pretreatment variables are related to
      outcome, there is little evidence relating to influential within-treatment
      variables. This study sought to examine a series of treatment variables against
      outcome. MATERIAL AND METHODS: A total of 66 children with severe primary
      nocturnal enuresis but with no day-time wetting were treated with a body-worn
      enuresis alarm. Pre- and within-treatment variables were collected. Success was
      considered to be 14 consecutive dry nights during a 16-week period. RESULTS: A
      total of 54.5% of children achieved the success criterion, with 12.1% being
      classed as partial successes. Of the pretreatment variables, only low functional
      bladder capacity was significantly associated with failure. Inability to be woken
      by the alarm emerged as the most important within-treatment predictor of failure.
      CONCLUSIONS: The success of alarm treatment is dependent on the child's ability
      to be aroused by the alarm. Interestingly, of those who successfully became dry,
      72.2% slept throughout the night for >80% of nights that they were dry,
      suggesting that the mode of action of the enuresis alarm is more complex than was
      previously thought.

PMID- 12201919
TI  - Real indications for adrenalectomy in renal cell carcinoma.
AB  - OBJECTIVES: We determined the incidence and characteristics of adrenal
      involvement in localized and advanced renal cell carcinoma, and evaluated the
      role of adrenalectomy as part of radical nephrectomy. PATIENTS AND METHODS: From
      1993 to 1999, 210 patients with renal cell carcinoma (RCC) (139 men and 71 women,
      mean age 60.8 years, range 12-96 years) underwent radical nephrectomy with
      associated adrenalectomy. Patients were divided into two subgroups of 106 with
      localized (stage T1-2 tumor, group 1) and 104 with advanced (stage T3-4N01M01,
      group 2) renal cell carcinoma. A retrospective review of preoperative
      computerized tomography (CT) of the abdomen was performed. Radiographic findings
      were subsequently compared with postoperative histopathological results to assess
      the predictive value of tumor characteristics and imaging in determining adrenal
      metastasis. RESULTS: Of the 210 patients, 15 (7.1%) had adrenal involvement.
      Tumor stage correlated with probability of adrenal spread, with T3-4 and T1-2
      accounting for 13.4% and 0.9% of cases, respectively (p < 0.001). Upper pole
      intrarenal RCC most likely to spread was local extension to the adrenal gland,
      representing 53.3% of adrenal involvement. In contrast, multifocal, lower pole
      and mid region RCC tumors metastasized hematogenously, representing 21.4%, 7%,
      and 14% of adrenal metastasis, respectively. The relationship between intrarenal
      tumor size (mean 7.8 cm, range 4-21) and adrenal involvement was not
      statistically significant. Preoperative CT demonstrated 97.7% specificity, 98.4%
      negative predictive value, 87% sensitivity and 80% positive value for adrenal
      involvement by RCC. CONCLUSIONS: Ipsilateral adrenalectomy should only be
      performed if a lesion is seen preoperatively on CT scan or if gross disease is
      seen at the time of nephrectomy. The prognosis is poor for RCC with ipsilateral
      involvement even with complete removal. Because of this poor prognosis we believe
      that adrenal involvement should constitute a separate stage category.

PMID- 12201920
TI  - Nephropexy ad modum Albarran Marion: long-term follow-up.
AB  - OBJECTIVE: To report a long-term follow-up of nephropexy ad modum (a.m.) Albarran
      Marion. MATERIAL AND METHODS: Between 1980 and 1999, 18 women (mean age 42.6
      years) underwent nephropexy a.m. Albarran Marion. The duration of symptoms varied
      from 7 months to 9 years. All patients were examined preoperatively using
      excretory urography and renography in both the supine and erect positions in
      order to document renal descent. Patients with decreased renal function also
      underwent postoperative renography. A questionnaire concerning pre- and post
      treatment symptoms was sent to all patients. RESULTS: Hospitalization averaged
      7.2 days (range 4-15 days). Pneumothorax occurred in 7 patients, 3 of whom
      required temporary drainage. One patient developed pneumonia and another a
      retroperitoneal haematoma; no other complications occurred. All postoperative
      renography findings were normal. Median follow-up time was 11.2 years (range 2-21
      years). At follow-up, 87.5% of patients were satisfied with the results and were
      free from pain. Two patients were not satisfied with the results; retrospectively
      the indications for surgery in these 2 cases were not absolute. CONCLUSIONS:
      Operative treatment for symptomatic nephroptosis should only be performed in
      selected cases. We present a success rate of 87.5% for nephropexy a.m. Albarran
      Marion, at a mean follow-up of 11.2 years, which equals the best results obtained
      with other procedures. The choice of operative procedure for symptomatic
      nephroptosis must be based on the special interests and skills available at the
      institutions concerned.

PMID- 12201921
TI  - Comparison of three analgesics for extracorporeal shock wave lithotripsy.
AB  - OBJECTIVE: The aim of the study was to compare the clinical efficacy of three
      different analgesic drugs with respect to their level of sedation, analgesia and
      quick mobilisation without cardiopulmonary depression, for outpatient
      extracorporeal shock wave lithotripsy (ESWL) procedure. MATERIAL AND METHODS:
      Sixty outpatients undergoing elective ESWL using a third generation lithotriptor
      were studied. The patients were randomly divided into three groups of twenty
      patients. All patients received midazolam (2 mg) intravenously five minutes
      before the procedure. In group F, fentanyl was given (1 microg kg(-1) IV) at the
      same time with midazolam. In group D, diclofenac sodium was given (1 mg kg(-1),
      IM) intramuscularly 45 minutes before ESWL. In group T, tramadol was given (1.5
      mg kg(-1)) 30 minutes before ESWL. Arterial pressure, heart rate, respiratory
      rate and oxygen saturation were recorded before the procedure, after sedation, at
      the first minute, and every ten minutes during the procedure. Pain intensity was
      identified with a Visual Analogue Scale. The level of sedation was evaluated by
      using the Observer's Assessment of Alertness/Sedation Scale. All patients were
      asked to assess their satisfaction with the seven point Verbal Rating Scale
      before discharge. Side-effects were also recorded during the procedure. RESULTS:
      The incidence of nausea and vomiting was higher in fentanyl group compared with
      the other groups. In patients who received fentanyl, the decrease of oxygen
      saturation at the first and tenth minute of the procedure was statistically
      significant (p < 0.05). CONCLUSIONS: Diclofenac sodium and tramadol were found to
      be safe and effective analgesics with lower side-effects than fentanyl.

PMID- 12201922
TI  - Cost-effectiveness of new treatments for benign prostatic hyperplasia: results of
      a randomized trial comparing the short-term cost-effectiveness of transurethral
      interstitial laser coagulation of the prostate, transurethral microwave
      thermotherapy and standard transurethral resection or incision of the prostate.
AB  - OBJECTIVES: To compare the short-term cost-effectiveness of ILC and TUMT with
      that of transurethral resection or incision of the prostate in patients with
      symptomatic benign prostatic hyperplasia. MATERIAL AND METHODS: One hundred and
      eighteen patients were randomized to ILC, TUMT and TUR-P/TUI-P in 2:2:1 fashion.
      The use of resources within the first 6 months of follow-up were measured and the
      cost of treatment for each patient were calculated. A few parameters, primarily
      related to the time spent by the staff, were measured only in a subgroup of
      patients. A cost-effectiveness analysis was performed based on the average
      calculated cost and change in I-PSS found in each group. For costly resources a
      sensitivity analysis was performed. RESULTS: At 6 months the cost was lowest in
      the TUMT group and highest in the ILC group. The cost-effectiveness ratio (C/E)
      was 763 DKK/point reduction in I-PSS in the control group and 1.200 and 938 in
      the ILC and TUMT group, respectively. An incremental analysis demonstrated that
      TUR-P/TUI-P dominated ILC. In a similar comparison of the TUMT and the TUR-P/TUI
      P group an incremental ratio of 170 DKK/extra point of reduction in I-PSS was
      found in the TUR-P/TUI-P group. CONCLUSION: In the short-term TUMT and TUR-P has
      comparable cost-effectiveness. TUR-P was slightly more effective than TUMT, but
      the cost was also slightly higher. In our set-up of ILC the short-term cost
      effectiveness of ILC was inferior to that of TUR-P. Conclusions should be made
      with caution, since the follow-up at present is short.

PMID- 12201923
TI  - Psychological problems in young men with chronic prostatitis-like symptoms.
AB  - OBJECTIVE: To take a different perspective in assessing young men with chronic
      prostatitis-like symptoms, this study was designed since few prospective studies
      are available to survey a population of young men. MATERIAL AND METHODS: One
      hundred and fifty men aged 20 years dwelling in the community were randomly
      selected. Chronic prostatitis-like symptoms were measured by the National
      Institutes of Health-Chronic Prostatitis Symptom Index and the selfreported
      scores for pain and urinary symptoms were used to identify chronic prostatitis
      like symptoms. The psychological methods used were the Beck Depression Inventory,
      the State-Trait Anxiety Inventory, and the Bem Sex Role Inventory. A total of 87
      men (a response rate 58%) completed self-administered questionnaires. RESULTS: As
      the scores for pain and urinary symptoms increased, those for depression
      increased (p < 0.001 and p = 0.01, respectively). However, the mean scores for
      state and trait anxiety were not different according to the scores for pain and
      urinary symptoms. The mean masculinity scores were not different according to the
      scores for pain but those were significantly different according to the scores of
      urinary symptoms (p = 0.042). The mean femininity scores were not different
      according to the scores of pain and urinary symptoms. CONCLUSIONS: Our findings
      suggest that psychological factors, especially depression and weak masculine
      identity may be associated with an early stage of chronic prostatitis-like
      symptoms. Young men with chronic prostatitis-like symptoms also have
      psychological problems.

PMID- 12201924
TI  - Ischemia, whether from ligation or torsion, causes ultrastructural changes on the
      contralateral testis.
AB  - OBJECTIVE: Unilateral testicular torsion results with a decrease in contralateral
      testicular blood flow caused by a reflexive sympathetic response. The aim of this
      study was to investigate whether twisting of the spermatic cord, or testicular
      ischemia without twisting, activates this reflex mechanism and causes
      ultrastructural changes in the contralateral side. MATERIALS AND METHODS: Thirty
      adult male albino Wistar rats were randomly allocated into three groups of sham,
      torsion, and ligation. Right testes were twisted 720 degrees counterclockwise in
      the torsion group. Right spermatic cords were ligated permanently with a silk
      suture including the vas deferens in the ligation group. After 24 h of testicular
      ischemia, contralateral left testes were removed for electron microscopic
      evaluation. RESULTS: Contralateral testes showed similar ultrastructural changes
      in the torsion and ligation groups. The fibrous tunica propria enveloping the
      seminiferous tubule was thickened due to increased collagen fibers. The basal
      lamina was continuous but thickened and showed several foldings. The gap between
      basal lamina and the germ cells was increased because of collagen fibers. Leydig
      cells showed mitochondrial degeneration with the loss of its cristae. Leydig
      cells lost their contact with its neighborhood cells in some areas, and these
      gaps were filled with collagen fibers. Germ cells showed dilated cisternae of
      smooth endoplasmic reticulum, cytoplasmic electron-dense bodies and clear
      regions. CONCLUSIONS: Similar electron microscopic findings observed in the
      torsion and ligation groups indicate that testicular ischemia rather than
      twisting of the spermatic cord is responsible for the ultrastructural changes in
      the contralateral side.

PMID- 12201925
TI  - Tunica albuginea plication for the correction of penile curvature.
AB  - OBJECTIVE: To evaluate the efficacy of tunica albuginea plication (TAP) in the
      correction of congenital and acquired penile curvatures and determine key points
      for a successful outcome of this procedure. MATERIALS AND METHODS: From December
      1995 to January 2001, 40 patients with penile curvature (10 congenital and 30
      secondary to Peyronie's disease) underwent surgical correction by TAP.
      Indications were difficult or impossible penetration, normal erectile function,
      stable disease. For TAP we used non-absorbable inverted stitches tied with the
      assistant pushing down the tunica albuginea with a mosquito clamp to create an
      adequate groove for the knot. The results were evaluated subjectively and
      objectively. RESULTS: At mean follow-up of 30 months, full subjective and
      objective success (straight penis, mild shortening, normal erection, penetration
      and sensation) was achieved in 37 (92.5%) patients. Objective but not subjective
      success was achieved in 2 patients (5%), 1 complaining of psychogenic erectile
      dysfunction and the other of excessive penile shortening. There was only one
      failure, namely persistent glans numbness due to damage of the non-mobilized
      neurovascular bundle. CONCLUSIONS: TAP is a simple and effective method for the
      correction of congenital and acquired penile curvatures. Key points for
      successful outcome are adequate preoperative evaluation and counselling, careful
      preparation of tunica albuginea, mobilization of urethra or neurovascular bundle
      when needed, use of inverted stitches carefully buried, objective postoperative
      evaluation with a pharmacological erection test.

PMID- 12201926
TI  - Transrectal core biopsy trauma may increase cell proliferation in prostate
      tumors.
AB  - Whilst analyzing the morphological effects of a 3-week dietary intervention in
      patients with prostate cancer, we made an unexpected observation to the effect
      that prostate biopsy trauma may, at least transiently, increase prostate tumor
      cell proliferation. Further studies are needed to evaluate the clinical
      significance of this observation.

PMID- 12201927
TI  - Severe symptomatic osteoporosis in patients on androgen deprivation therapy for
      prostatic carcinoma.
AB  - We report 3 patients referred to the bone clinic after spinal fractures. Dual
      energy X-ray absorptiometry showed severe osteoporosis. Each patient was found to
      have a history of prostatic carcinoma and long-term treatment with goserelin. We
      suggest that all patients who have received androgen deprivation therapy for more
      than 1 year should be evaluated by bone densitometry.

PMID- 12201928
TI  - Fournier's gangrene following penile self-injection with cocaine.
AB  - To date, there have been no reports of Fournier's gangrene following penile self
      injection of cocaine. We report a case of cocaine-induced Fournier's gangrene
      requiring parenteral antibiotics followed by primary surgical debridement and
      delayed reconstructive procedure of penile skin.

PMID- 12201929
TI  - Renal water and sodium handling during gradated unilateral ureter obstruction.
AB  - OBJECTIVE: Unilateral complete obstruction of the ureter (UUO) is associated with
      characteristic changes in renal function. To improve the understanding of how
      urine concentration directly is affected by changes in pelvic pressure, changes
      in renal salt and water handling along the nephron and collecting duct were
      examined. MATERIAL AND METHODS: Pelvic pressure was raised stepwise using an
      adjustable lever inserted in the right ureter. Urine samples were collected from
      the tip of the catheter by way of an overflow system. Water and sodium handling
      in the distal and proximal tubules were measured by the lithium clearance
      technique. Renal blood flow (RBF) was measured with implanted ultrasonic flow
      probes. Catheters were placed in both renal veins and glomerular filtration rate
      (GFR) and filtration fraction were calculated using renal extraction of (51)Cr
      EDTA independent of urine sampling. RESULTS: The sequence of changes for each
      parameter is provided. The parameters did not show a uniform pattern from which
      specific threshold values could be derived. However, the mean value of the
      following parameters were markedly changed at specific pressures: (1) at 10 cm
      H(2)O ipsilateral urine output decreased rapidly and distal absolute reabsorption
      of sodium (DAR(H2O)) decreased, (2) at 20 cm H(2)O GFR started to decline
      rapidly, (3) at 30 cm H(2)O urine output was impaired, and (4) at 40 cm H(2)O
      proximal absolute reabsorption of water (PAR(H2O)) showed a decreasing tendency
      in all pigs together with impairment in tubular sodium handling. Furthermore,
      free water clearance was slightly impaired (-0.26 +/- 0.15 at baseline and -0.15
      +/- 0.08 ml/min at maximum pressure) and ipsilateral RBF decreased from 171.1 +/-
      12.4 ml/min at baseline to 136.3 +/- 12.3 ml/min at ureteral pressure of 80 cm
      H(2)O (p < 0.05). Consistent with that, ipsilateral renal vascular resistance
      increased with increasing pressure in the renal pelvis. CONCLUSION: Water
      reabsorption and sodium handling is progressively impaired with increasing pelvic
      pressure. GFR and RBF are reduced in parallel. The study shows that the kidney
      responds to ureteral obstruction is unique and individual.

PMID- 12201930
TI  - Changes in urethral connective tissue after estrogen replacement therapy in
      ovariectomized rats.
AB  - OBJECTIVE: Genuine stress urinary incontinence is a common problem after the
      middle age. Various treatment modalities have been tried as a treatment for this
      entity and estrogens are one of the most common alternatives. Their effects on
      the urethral mucosa have been described in many studies, while the impact on the
      urethral connective tissue has been evaluated only in a few reports. In this
      study, we aimed to investigate the effect of estrogen on urethral connective
      tissue in ovariectomized rats. MATERIAL AND METHODS: Thirty-six Wistar rats (4
      months old, 250-300 g weight) were included in the study. They were organized as
      group 1 (ovariectomized, n = 10), group 2 (ovariectomized + late estrogen
      treatment, n = 10), group 3 (ovariectomized + early estrogen treatment, n = 10)
      and group 4 (sham operated, n = 6). Rats in group 1 were killed 6 weeks after the
      ovariectomy. Group 2 was ovariectomized 6 weeks before treatment and then
      received estradiol for 6 weeks. Group 3 was treated with estradiol for 6 weeks
      immediately after the ovariectomy. After killing the rats, urethral tissues were
      removed. Quantitative analysis of collagen fiber content was done by computerized
      image analyzer system in specimens stained with Masson's trichrome technique.
      RESULTS: Percentages of collagen fiber content (mean +/- standard error of mean)
      were 58.4 +/- 5.9% in group 1; 53.3 +/- 4.8% in group 2; 46.3 +/- 3.4% in group 3
      and 40.2 +/- 3.2% in group 4. There was not any significant difference among the
      groups (p > 0.05). CONCLUSIONS: Our results suggest that early and late estrogen
      replacements do not seem to have a discriminating effect on the urethral
      connective tissue. Further studies are needed to assess the preventive effect of
      estrogen on urethra.

PMID- 12201931
TI  - Urinary bladder volume measurements: comparison of three ultrasound calculation
      methods.
AB  - OBJECTIVE: To assess the precision of three different automatic calculation
      methods in real-time bladder volume measurement. MATERIAL AND METHODS: Bladders
      from 34 medical staff volunteers were examined. Two examinations of each subject
      were performed independently by 2 examiners using 2 identical ultrasound scanners
      with no delay between the examinations. Three different automatic calculation
      algorithms, available as software in the ultrasound scanner, were applied on the
      frozen ultrasound pictures. After registration of the voided volume with an
      uroflowmeter, the subjects were scanned again in order to assure complete
      emptying. RESULTS: Voided volumes ranged from 45 ml to 508 ml. The precision of
      each method was equal but the LWH method measured significantly lower values than
      the ELLIPSOID and AREA method. Errors in the range of -56.1% to +58.8% for all
      volumes and methods were found. Data for voided volumes greater than 150 ml (n =
      29) were investigated separately, but no significant improvement in accuracy for
      any of the methods was found. CONCLUSIONS: Ultrasound bladder volume calculation
      is an easy method for estimation of bladder volume. The prolate ellipsoid method
      (LWH) is recommended as the standard calculation method because it is fast and
      easy. Unacceptable large measure errors are found and too rigid conclusions based
      on ultrasound measurements of bladder volume should be avoided.

PMID- 12201932
TI  - Effects of finasteride on vascular endothelial growth factor.
AB  - OBJECTIVE: Finasteride has been shown to reduce prostate bleeding in patients
      with benign prostatic hyperplasia (BPH). The mechanisms behind this are not
      known, but it has been suggested that finasteride reduces bleeding by inhibiting
      angiogenesis in the prostate. Studies in animals have shown that castration
      rapidly induces involution of the prostate vasculature, and androgen-stimulated
      prostate growth may be angiogenesis dependent. The objective of this study was to
      explore the response to finasteride on the vasculature and the expression of
      vascular endothelial growth factor (VEGF), a potent regulatory factor of
      angiogenesis in human prostate tissue. MATERIAL AND METHODS: Patients with BPH
      were randomly assigned to 3 months of treatment either with finasteride (5
      mg/day) or placebo before undergoing transurethral resection of the prostate
      (TURP). Prostate tissue VEGF expression was quantified by Western blot and the
      vascular density determined in Factor VIII immunostained tissue sections. Serum
      concentrations of VEGF were measured with ELISA technique. RESULTS: Patients
      treated with finasteride (n = 15) showed a decrease in prostate tissue VEGF(165)
      expression compared with placebo (n = 13) treated patients (p < 0.05), but the
      vascular density and the serum VEGF levels were unaffected. CONCLUSIONS: This
      study shows that finasteride treatment decreases VEGF expression in the human
      prostate.

PMID- 12201933
TI  - Increased bladder apoptosis with alpha-1 adrenoceptor antagonists in benign
      prostatic hyperplasia.
AB  - OBJECTIVE: To determine whether preoperative usage of alpha-1 adrenoceptor
      antagonists (alpha-1ARA) prevents the alterations in bladder wall components due
      to obstruction via changing apoptotic and/or proliferative activity and provides
      an advantage for improvement of irritative symptoms following removal of bladder
      outlet obstruction. MATERIAL AND METHODS: A total of 39 patients were enrolled to
      the present study. According to preoperative medical treatment, patients were
      divided into 2 groups as preoperative untreated (n = 15) and medically treated
      patients with alpha-1ARA (n = 24). Apoptotic and proliferative indices of bladder
      wall were determined with TUNEL assay and proliferating cell nuclear antigen
      immunoreactivity, respectively. RESULTS: While the mean apoptotic indexes (AI) of
      lamina propria were 0.293 +/- 0.163 vs 0.978 +/- 0.194 in untreated and treated
      patients, the mean AI of myofibroblast cells were 0.10 +/- 0.06 and 0.90 +/- 0.23
      in untreated and treated patients, respectively. There were statistically
      significant differences between lamina propria (p = 0.0067) and myofibroblast
      cells (p = 0.0280) AI in the two groups. However, there were no significant
      differences between postoperative symptom indices in preoperatively treated and
      untreated groups. CONCLUSIONS: alpha 1-ARA treatment might have an effect on
      hypertrophy and supersensitivity of bladder wall due to increased outlet
      obstruction via prevention of the imbalance between cell proliferation and
      apoptosis, providing normal homeostatic control mechanisms, through the interval
      between the onset of the lower urinary tract symptoms and time surgical
      intervention. However, further studies should be organized to demonstrate the
      impact of long-term alpha 1-ARA medication for post-operative significant
      improvement on irritative symptom index.

PMID- 12201934
TI  - The treatment of sphincter incontinence with periurethral silicone implants
      (macroplastique).
AB  - OBJECTIVE: Patients with genuine stress urinary incontinence (GSI) refractory to
      conservative measures often undergo a colposuspension when the reason for urine
      leakage is hypermobility of the bladder neck. Patients who suffer from an
      insufficiency of the intramural sphincter are instead often suitable for
      pubovaginal sling procedures, implantation of an artificial sphincter or
      peri/intraurethral injection of some expansion substance. Here, we present our
      experience of periurethral injection of silicone microimplants (Macroplastique).
      METHOD: We studied 8 men and 22 women with urodynamically stable detrusor, and
      validated GSI on a standardized quantification test. Under direct endoscopic
      control Macroplastique was injected. Follow-up was performed by a questionnaire
      and a new standardized quantification test. RESULTS: Nineteen of the 22 patients
      with follow-up in excess of 2 years reported a considerable amelioration and
      their subjective impressions were also validated by the postoperative
      standardized quantification test (preoperative 147 g, postoperative 9 g; p <
      0.001). No side effects were reported except for mild dysuria for practically all
      the patients, in all cases transient. A few patients also reported a short
      initial sensation of incomplete bladder emptying. CONCLUSION: Considering the
      difficulty in treating sphincter insufficiency, particularly iatrogenic, the
      results in this study appear to justify the attempt of injection therapy. It may
      very well be performed as an outpatient procedure and, moreover, side effects are
      rare. If silicone microimplants are used there is no obstacle to proceed with
      artificial sphincter implantation, should the patient's symptoms remain
      unaffected by the injection procedure.

PMID- 12201935
TI  - Enuresis and the effective factors--a case-control study.
AB  - OBJECTIVE: Enuresis is widespread and affects the child and the family both
      psychologically and socially. This research was performed between 1 February and
      30 June 1998, in Gemlik district to investigate the effective factors on enuresis
      among 5-9 year-old children. MATERIAL AND METHODS: A questionnaire containing 31
      questions was answered by the mothers during the house visits. Two hundred and
      seventy-seven cases were determined in a previous study and randomly selected 277
      controls were matched according to their ages, gender and residential districts.
      RESULTS: Younger mothers, mothers with less education and working mothers have
      more enuretic children. Enuresis is more prevalent within the first children.
      Odds ratio is 11.1 if his/her mother and/or father has had enuresis. The age of
      toilet training was earlier among controls than cases. CONCLUSIONS: As enuresis
      is rather widespread, the parents may consider this as a transient problem and
      therefore no effort might be given for the solution. Trained health personnel and
      physicians should enlighten the parents about enuresis in order to eliminate the
      negative effect on the child.

PMID- 12201936
TI  - An investigation of the impact of nocturnal enuresis on children's self-concept.
AB  - OBJECTIVE: This study sought to evaluate the relationship between the self-esteem
      and the self-image of children with nocturnal enuresis and to examine these in
      relation to various aspects of clinical and demographic variables. Previous
      studies investigating the self-esteem of bedwetting children have had mixed
      findings. Some studies report that children with nocturnal enuresis have a lower
      self-esteem than their non-bedwetting peers, but other studies report that
      children with nocturnal enuresis perceive themselves similarly to non-bedwetting
      children. However, what have not been studied to date are the self-perceptions of
      bedwetting children treated in community clinics. MATERIAL AND METHODS: A total
      of 114 bedwetting children treated in community clinics provided the sample.
      School nurses conducted a routine first-visit assessment, collected baseline
      demographic and social information and invited children to complete the Butler
      Self-Image Profile and the Coopersmith Self-Esteem Inventory. RESULTS: Age and
      extent of wetting were not significantly related to self-concept measures. Girls
      had significantly (p = 0.008) higher scores on positive self-image compared with
      boys. Children with secondary enuresis also scored higher on positive self-image
      compared with those with primary nocturnal enuresis (p = 0.02). The Butler self
      image scores indicated a number of significant links between positive self-image
      and enuresis variables, whereas the Coopersmith self-esteem scores generally
      failed to distinguish between the enuresis variables and closely reflected those
      of the negative self-image scores. CONCLUSIONS: These findings suggest that
      amongst children with nocturnal enuresis, the most vulnerable in terms of self
      image are male, those with primary enuresis and those with a greater number of
      wet nights a week.

PMID- 12201937
TI  - Effect of diuresis on extracorporeal shockwave lithotripsy treatment of ureteric
      calculi.
AB  - OBJECTIVE: To evaluate the effect of diuresis during extracorporeal shockwave
      lithotripsy (ESWL) treatment of ureteric calculi. The purpose is to improve stone
      fragmentation and clearance rates. MATERIALS AND METHODS: One hundred and six
      consecutive patients with ureteric calculi at different levels were treated by
      ESWL using Siemens Lithostar 2 machine. Patients have been randomized into two
      treatment groups. The first group was treated by standard ESWL and included 54
      patients. The second group was treated by ESWL with diuresis during the ESWL
      session. Shock waves were given at a rate of 90 shocks/minute with energy
      starting from 10 up to 18 KV. During the ESWL session the patient belonging to
      the second group received i.v. infusion of 500 ml normal saline containing 40 mg
      furosemide as a diuretic. The stone fragmentation and clearance rates were the
      two end points for evaluation. RESULTS: The average number of sessions per stone
      was 1.92 and 1.5 and the average number of shocks per stone was 6295 and 5300 for
      the first and second treatment groups respectively. Stone fragmentation rate was
      47/54 (87%) and 50/52 (96.2%) and the stone clearance (success) rate was 47/54
      (87%) and 48/52 (92.3%) for the first and the second groups respectively.
      Analysis of the results in relation to stone location showed that the two
      treatment groups were comparable for upper and middle ureteric calculi. However
      for distal ureteric stones, the addition of diuresis during ESWL was associated
      with a lower mean number of ESWL sessions and shocks per stone compared with
      standard ESWL: 1.38 and 4950 for ESWL with diuresis compared with 2.9 and 8544
      for standard ESWL respectively. The stone fragmentation and 3-month clearance
      (success) rates were clearly higher: 93.8% and 87.5% respectively for ESWL with
      diuresis compared with 70.6% (for both fragmentation and clearance) with standard
      ESWL. CONCLUSIONS: Diuresis is a useful, inexpensive and safe adjunct to ESWL of
      ureteric stones. It markedly improves the results of ESWL treatment of distal
      ureteric stones compared with standard ESWL.

PMID- 12201938
TI  - Suspicious urine cytology (class III) in patients with bladder cancer: should it
      be considered as negative or positive?
AB  - OBJECTIVES: Urine cytology is the gold standard in the diagnosis and follow-up of
      bladder cancer. Cytology, however, exhibits variable sensitivity depending on
      tumour grade and interpretation of urine specimens is highly dependent on the
      skill of the examiner. Positive cytology, classes IV and V by Papanicolaou
      classification, is a strong predictor for coexisting or subsequent malignancy,
      while the role of suspicious cytology, class III, is controversial. The objective
      of the study was to evaluate the role of the suspicious finding in cytological
      analysis, and whether it should be considered as a negative or positive sign for
      coexisting malignancy. MATERIAL AND METHODS: Six hundred and fifty-two
      consecutive patients with bladder cancer were studied in a prospective
      multicenter trial. One hundred and fifty-one of the patients were newly
      diagnosed, and the remaining 501 patients were under follow-up. A voided urine
      sample was obtained prior to TURB or prior to routine follow-up cystoscopy in
      those under the surveillance and split for culture and cytology. The
      cytopathological results were analyzed by a central review and only patients with
      samples available for review analysis were included. Sensitivity and specificity,
      as well as positive (PPV) and negative (NPV) predictive values of urine cytology
      were calculated by classifying the class III samples as negative or positive.
      RESULTS: A total of 570 patients were evaluable. One hundred and twenty nine
      (22.6%) were newly diagnosed and 441 were under follow-up, of whom 117 (26.5%)
      had recurrence. Cytology was classified as suspicious in 33/129 (25.6%) patients
      with primary tumour, and in 41/441 (9.3%) of those under the follow-up, of whom
      20 (48.8%) had recurrence. Sensitivity increased from to 31.0% to 56.6% in
      primary tumours (p < 0.001) and from 17.8% to 34.7% in recurrent tumours (p <
      0.001) if class III was determined as positive, whereas the specificity decreased
      from 96.6% to 90.1% (p < 0.001). Accordingly, the NPV increased from 76.3% to
      79.1% and the PPV decreased from 65.6% to 56.2%. CONCLUSIONS: The poor
      sensitivity of voided urine cytology improved significantly when suspicious
      samples were determined as positive while the specificity remained high, a clear
      advantage compared with most of the new tumour marker tests. In addition, nearly
      half of the follow-up patients with suspicious class III cytology had recurrence
      implying that this patient category is at substantial risk for co-existing
      malignancy. Therefore, it is recommended that suspicious class III cytology
      together with class IV and V specimens should be considered positive.

PMID- 12201939
TI  - Intravesical instillations of interferon gamma in the prophylaxis of high risk
      superficial bladder cancer--results of a controlled prospective study.
AB  - OBJECTIVE: To determine if intravesically administered recombinant interferon
      (IFN) gamma may serve as adjuvant first line treatment in prophylaxis of
      superficial bladder cancer by reducing its risk for recurrence, in the short
      term. MATERIAL AND METHODS: A total of 54 patients (43 males and 11 females) with
      superficial bladder tumours (Ta/T1) initially treated with transurethral
      resection for their tumors were randomized into two groups: Twenty-eight patients
      were left untreated after the transurethral resection (controls) whereas 26
      patients received intravesical IFN gamma adjuvantly, at a dosage of 0.7 mg per
      week for 8 weeks. Patients with G1 tumors and carcinoma in situ were excluded.
      The follow up had a mean time of 12.1 months. Recurrence or progression, as
      terminal events of the study, were recorded. The comparison of the recurrences
      between the two groups was performed by estimating: (a) the simple recurrence
      rate, and (b) the interval to tumor recurrence in each group. RESULTS: Tumor
      recurrence was detected in 24 controls (86%) and in 16 (62%) patients of the IFN
      gamma group (p = 0.043). The comparison of the Kaplan-Meier disease-free survival
      curves between the two groups of patients indicated that intravesical
      instillations of IFN gamma exerted a continuous protective effect to those who
      received the agent, in the follow up period (p = 0.0237). No serious side-effects
      were noted. CONCLUSIONS: Intravesically administered IFN gamma has a demonstrable
      protective role as first line adjuvant treatment in superficial bladder cancer.
      This role is mainly focused on prevention of recurrences in the short term.
      Further prospective studies with longer follow up are required, in order to
      define the exact place of the drug in the urologist's armamentarium.

PMID- 12201940
TI  - Intratesticular lipoma.
AB  - Benign intratesticular lesions are rare. We describe the second reported case of
      an intratesticular lipoma and discuss the limitations of ultrasonography in
      differentiating benign from malignant conditions occurring within the testis.

PMID- 12201941
TI  - Prostate cancer metastatic to the omentum.
AB  - A 76-year-old man presented with palpable omental metastasis and gross ascites
      due to prostate cancer. Within 3 months of surgical castration, the ascites
      resolved completely, the omental mass was reduced by more than 75%, and serum PSA
      fell to 4.24 ng/ml from 368.4 ng/ml. Worthwhile palliation can be achieved in
      patients with massive effusions secondary to metastatic prostate cancer using
      hormone manipulation.

PMID- 12201942
TI  - Renal cell carcinoma (chromophobe type) in the first trimester of pregnancy.
AB  - We report a case of renal cell carcinoma (chromophobe type) in a female in the
      first trimester of her first pregnancy. The tumour was removed completely.
      Postoperatively single live pregnancy was confirmed and subsequently resulted in
      spontaneous vaginal delivery at term of a healthy infant.

PMID- 12201943
TI  - Atypical leiomyoma of the urinary bladder--a rare tumor occurring in a young
      female with concurrent breast carcinoma--an influence of sex steroid hormone?
AB  - Smooth muscle tumors are uncommon in the urinary bladder, and atypical leiomyoma
      of the urinary bladder is extremely rare. We report a case of atypical leiomyoma
      with a concurrent breast carcinoma and discuss the pathologic features, the
      possible etiology and clinical outcome of the tumor.

PMID- 12201944
TI  - Prostatic urethral leukoplakia with prostatic abscess.
AB  - We present a case of prostatic abscess and coexistent leukoplakia of the urethra
      in a 51-year-old man. He had been suffering from diabetes mellitus for 10 years
      and following cessation of high fewer, transurethral electrovaporesection was
      performed.

PMID- 12201945
TI  - Hematotherapy for AIDS.

PMID- 12201946
TI  - Takayuki Asahara, M.D., PH.D. Interview by Vicki P. Glaser.

PMID- 12201947
TI  - New therapies in leukemia: renewed hope.

PMID- 12201948
TI  - A review of the Wilms' tumor 1 gene (WT1) and its role in hematopoiesis and
      leukemia.
AB  - One of the first clones of the Wilms tumor 1 (WT1) gene, WT33, was isolated from
      a B cell leukemia cell line in 1990. Now, 12 years on, WT1 has emerged as a
      potentially important target for antileukemic therapies. Our understanding of the
      role that WT1 plays during normal hematopoiesis is still limited, and there is a
      large amount of conflicting data concerning the precise manner in which WT1 gene
      expression contributes to leukemogenesis. However, interest in this field has
      intensified in the past 5 years. This review surveys the progress made in this
      area.

PMID- 12201949
TI  - Role of dendritic cells in graft-versus-host disease.
AB  - A major barrier to successful allogeneic hematopoietic stem cell transplantation
      is graft-versus-host disease (GVHD). Until recently, the role of antigen
      presentation in the development of this disorder was unknown. The experimental
      finding that recipient antigen-presenting cells (APCs) were required for the
      development of CD8(+) T cell-dependent GVHD has led to a fundamental reappraisal
      of our ideas concerning the pathogenesis of this disease. Following
      transplantation, the origin (donor or recipient), number, lineage, and function
      of APCs within the recipient are altered significantly. Studies that test the
      influence of each of these factors upon graft-versus-host responses, including
      graft-versus-tumor responses, are beginning to emerge and suggest that APCs, such
      as dendritic cells, constitute a potential target for therapeutic manipulation.

PMID- 12201950
TI  - Fetal hematopoietic stem cell transplantation: a challenge for the twenty-first
      century.
AB  - Successful in utero hematopoietic stem cell transplantation will likely represent
      a major step forward in the management of patients with congenital hematological,
      metabolic, and immunological disorders. We review the naturally occurring models
      of hematopoietic chimerism in animals and humans, as well as available
      experimental animal data and human clinical attempts of fetal transplantation.
      Data available from naturally occurring models and experimental models of fetal
      transplantation suggest that this technique should be translatable to the human
      fetus. However, to date, the success of human fetal hematopoietic stem cell
      therapy has been limited to fetuses with severe immunologic defects. Evaluation
      of successful attempts of human transplantation, the ontogeny of fetal immune
      development, and data available from animals provide insights into innovative
      approaches to fetal therapy that may bring the reality of successful fetal
      transplantation closer.

PMID- 12201951
TI  - Peripheral blood progenitor cell collection in low-weight children.
AB  - Peripheral blood progenitor cells (PBPC) are substituting bone marrow as a source
      of stem cells for either autologous or allogeneic hematopoietic transplantation.
      Several papers have been published on the experience of various groups in their
      mobilization and transplantation in children. Some technical problems have
      derived from the size of the patient or donor in the pediatric setting. Thereby,
      there is some concern regarding leukapheresis in very small children (weighing
      less than 15-20 kg). This paper summarizes our own data and that of other groups
      for the mobilization and collection of PBPC in the smallest children. Data from
      the literature show that mobilization with cytokines alone or in combination with
      chemotherapy is well tolerated by these patients. Pediatric donors may be used
      for allogeneic transplantation with no higher incidence of complications. PBPC
      collection even in the smallest children is a safe and efficient procedure when
      performed by experienced apheresis teams.

PMID- 12201952
TI  - Hepatic oval (stem) cell expression of endothelial differentiation gene receptors
      for lysophosphatidic acid in mouse chronic liver injury.
AB  - Growth factor lysophosphatidic acid (LPA) regulates cell proliferation and
      differentiation and increases motility and survival in several cell types, mostly
      via G-protein-coupled receptors encoded by endothelial differentiation genes
      (EDG). We show herein that hepatic oval (stem) cell proliferation, induced by 3,5
      diethoxycarbonyl-1,4-dihydrocollidine (DDC) in a mouse model of chronic liver
      injury, was associated with the expression of LPA1, LPA2, and LPA3 receptor
      subtypes; only LPA1 receptor protein was detectable in normal liver by western
      blot. In the injured liver, enhanced LPA1 receptor was identified predominantly
      in oval cells along the portal tract, proliferating ductular epithelial cells,
      and small cells, which were located in the nearby parenchyma and formed clusters.
      Interestingly, the LPA1 receptor was co-expressed in DDC-treated livers with the
      stem cell antigen SCA-1, suggesting that this receptor may be associated with
      bone marrow-derived progenitors. All three receptors for LPA were detected mostly
      in small cells in the vicinity of the portal tract, and co-localized with the A6
      antigen, a marker of ductular oval cells. In addition, hepatic levels of
      endogenous LPA were significantly higher in DDC-fed mice compared to normal
      animals. We propose that the expression of diverse LPA receptors may be a
      necessary part of the mechanism responsible for activation of oval cells during
      liver injury. As a result, LPA and its analogs may represent critical endogenous
      mediators, which regulate survival, increase motility, and modulate proliferation
      and differentiation of hepatocyte progenitors in regenerating liver.

PMID- 12201953
TI  - Large-scale generation of natural killer lymphocytes for clinical application.
AB  - Natural killer (NK) lymphocytes can be used for adoptive immunotherapeutic
      strategies. Alternatively, they may be employed as adjuvants for stem cell/bone
      marrow transplantation, either to re-induce remission, or to purge autografts of
      contaminating malignant cells. We developed a new protocol that enables the
      generation of NK cells on a clinical scale in a closed system that enables good
      manufacturing practice (GMP) conformity. Aside from the initial NK cell inoculum,
      our protocol includes activated feeder cells [irradiated peripheral blood
      mononuclear cells (PBMC) and no transformed blasts], cytokines [interleukin-2 (IL
      2) and IL-15], human serum, and a complex basic media formulation. During the
      whole expansion period of approximately 14 days, the cells were handled in PTFE
      (Teflon) bags, whereby fresh medium was added without opening the system. The use
      of immortalized or virus-transformed feeder cells, as used in many other current
      research protocols, was completely avoided. A precise controlling of a number of
      environmental factors was necessary to achieve reproducible results. Increases in
      NK cell number ranged between 80- and 200-fold. The resulting NK cells were
      CD56(+), CD3(-), and CD16(+) (75%). They were highly cytotoxic against different
      malignant target cells and did not produce significant levels of interferon
      gamma. Therefore, they belonged to the cytotoxic rather than the immunoregulatory
      NK subpopulation. No non-specific activation against normal allogenous
      lymphocytes occurred. This work might permit the realization of future protocols
      for evaluating the clinical effect of NK lymphocytes in human disease.

PMID- 12201954
TI  - Dendritic cell recovery following nonmyeloablative allogeneic stem cell
      transplants.
AB  - Nonmyeloablative allogeneic stem cell transplantation (NMSCT) may destroy some
      malignancies through a graft-versus-tumor (GVT) effect, but tumor relapse and
      viral reactivation remain challenges for which immunizations may be helpful.
      Dendritic cells (DC), particularly DC1 and ex vivo-cultured DC, induce antigen
      specific immune responses following viral infections and anti-tumor
      immunizations. DC2 may be tolerogenic. We hypothesize that successful
      immunizations following NMSCT will require adequate numbers of functional DC1 or
      ex vivo-generated DC. We determined the number, phenotype, and function of blood
      DC1 and DC2 and ex vivo-generated DC obtained from donor-recipient pairs before
      and up to 90 days after NMSCT. Although the percentage and number of recipient
      blood Lin(-) HLA-DR(+) CD11c(+) DC1 following NMSCT (median 0.46%, IQR 0.33
      0.52%) was lower than donor DC1 (median 0.94%, IQR 0.40-2.2%) this was not
      significant. In contrast, the percentage and absolute number of blood Lin(-) HLA
      DR(+) CD11c(-) CD123(+) DC2 was significantly decreased following the transplant
      (median 0.01% IQR 0.01-0.01% at day 60 compared with median 0.14%, IQR 0.10-0.38%
      for the donor before transplantation, p < 0.05). The yield (median 6.0%, IQR 5.5
      8.5%) and allostimulatory function of ex vivo-generated DC did not differ
      significantly at any time point. The donor chimerism of blood and cultured DC
      reflected that of the overall white blood cells. Ex vivo-generated, donor DC
      loaded with cytomegalovirus (CMV) antigens were capable of stimulating a CMV
      specific immune response in vitro within peripheral blood mononuclear cells of a
      patient following NMSCT. We conclude that blood DC numbers may be diminished
      following NMSCT transplant, but that DC1 recovery exceeds DC2 and functional DC
      may be generated from peripheral blood progenitors at all time points suggesting
      a possible use in immunization strategies.

PMID- 12201955
TI  - Cytolytic T cell reactivity to Epstein-Barr virus is lost during in vitro T cell
      expansion.
AB  - In the setting of allogeneic hematopoietic stem cell transplantation, ex vivo
      culturing of donor T lymphocytes is a necessary step for processes such as gene
      modification. Often the aim is to enable control of undesired alloreactivity
      after in vivo administration of the cultured cells. However, it is not fully
      understood how T cell reactivity against donor and third-party targets is
      affected by the ex vivo cell culturing process. We have assessed how the activity
      of anti-Epstein Barr virus (EBV)-specific T lymphocytes from healthy EBV
      seropositive donors is affected by in vitro cell culturing. Peripheral blood
      mononuclear cells (PBMCs) were expanded in X-VIVO 15 culture medium supplemented
      with 5% human serum. The cells were stimulated by either OKT3 (10 ng/ml) and
      interleukin (IL)-2 (500 U/ml) or by using anti-CD3/CD28-coated immunomagnetic
      beads and IL-2 (100 U/ml). Induction of polyclonal EBV-specific cytotoxic T
      lymphocyte cultures was attempted by stimulation of the in vitro-expanded cells
      at different time points during the cell expansion process, with pre-established
      autologous EBV-transformed lymphoblastoid cell lines (LCLs). While EBV-specific
      cytotoxic T lymphocytes (CTL) were generated from untreated PBMCs of 5 healthy
      donors, EBV-specific cytotoxicity was significantly decreased or absent in CTL
      cultures established from in vitro-expanded PBMCs. Our results indicate that the
      ex vivo cell expansion process itself significantly reduces the activity and/or
      the number of EBV-specific T cells. Additional stimulation with CD28 antibodies
      could not prevent this effect. Because T cell depleted bone marrow or stem cell
      grafts are known to contribute to the development of post transplant
      lymphoproliferative disorders, this should be taken into consideration if one
      considers expanding and administering PBMCs in conjunction with a T cell-depleted
      stem cell grafts.

PMID- 12201956
TI  - Induction of a hypercoagulability state and endothelial cell activation by
      granulocyte colony-stimulating factor in peripheral blood stem cell donors.
AB  - In June, 1997, we initiated a prospective study to analyze the effect of
      granulocyte colony-stimulating factor (G-CSF) on coagulation system in peripheral
      blood stem cells (PBSC) donors following G-CSF administration. Since, 25
      consecutively healthy donors received G-CSF (filgrastim) to mobilize and collect
      PBSC and 20 donors were finally included in the study. Blood samples were
      collected immediately before starting G-CSF and prior to PBSC collection to
      analyze the following parameters: prothrombin time (PT), activated partial
      thromboplastin time (APTT), fibrinogen, hypercoagulability markers (D-dimer, TAT
      complex, F1 + 2), natural anticoagulants (antithrombin, protein C, protein S),
      endothelial activation markers [von Willebrand factor antigen (vWF:Ag) and
      angiotensin converting enzyme (ACE)], and resistance to activated protein C. We
      found a significant increase in F1 + 2 and D-dimer while a significant decrease
      of antithrombin and protein C activity was evidenced. Regarding endothelial cell
      activation markers, a significant increase of vWF:Ag with a slightly significant
      decrease of ACE were also observed. Therefore, in PBSC donors receiving G-CSF our
      results reveal activation of both coagulation and endothelial cells that could
      favor the developing of thrombotic events. In consequence, a careful monitoring
      should be considered in those cases with risk factors for thrombosis.

PMID- 12201957
TI  - Mobilization and transduction of CD34(+) peripheral blood stem cells in patients
      with X-linked chronic granulomatous disease.
AB  - As a single-gene defect in phagocytes, the X-linked form of chronic granulomatous
      disease (X-CGD) is a disorder potentially amenable to gene therapy by transfer of
      a functional copy of the gp91(phox) gene into hematopoietic stem cells (HSC).
      Although antimicrobial agents and interferon-gamma (IFN-gamma) have significantly
      improved its prognosis, CGD is still associated with high morbidity and
      mortality. The disease can be cured by bone marrow transplantation (BMT);
      however, BMT in CGD has been associated with unacceptably high rates of
      morbidity, mortality, and graft failure, except in very selected cases in which
      an HLA-identical donor is available. Prerequisites for a clinical gene therapy of
      CGD are an efficient mobilization of peripheral blood stem cells (PBSC) as well
      as the preservation of their viability and hematopoietic potential following
      transduction and ex vivo culture. We show that (i) mobilization and collection of
      CD34(+) cells after a 4-week IFN-gamma-free period by G-CSF results in sufficient
      numbers of cells for transplantation; (ii) the quality of collected stem cells is
      not altered in comparison to cells obtained from healthy volunteers as assessed
      by long-term culture initiating cells (LTC-IC) and progenitor cell expansion;
      (iii) retroviral transfer of the gp91(phox) gene under defined, serum-free
      conditions leads to high and stable reconstitution of the respiratory burst
      activity in X-CGD neutrophils derived from transduced CD34(+) progenitor and LTC
      IC. Withdrawal of IFN-gamma in CGD patients may improve mobilization of CD34(+)
      stem cells by G-CSF. The gene transfer conditions established here are applicable
      to a clinical approach for gene therapy of X-CGD.

PMID- 12201958
TI  - Generation and characterization of human hematopoietic cell lines expressing
      factor VIII.
AB  - Considering the plasticity of hematopoietic stem cells (HSC), they would be ideal
      targets for gene therapy of hemophilia A by virtue of their progeny providing
      immediate access to the bloodstream. However, several attempts to show expression
      of recombinant factor VIII (rFVIII) by primary hematopoietic cells and cell lines
      have failed; this failure was attributed to the inability of HSC to secrete
      rFVIII. Here we describe the generation of stable, FVIII-secreting hematopoietic
      cell lines representing different blood-cell types using a bicistronic lentiviral
      vector encoding for a B-domain-deleted FVIII (FVIII Delta B) and enhanced green
      fluorescence protein (EGFP). Transduced cell lines with erythroid and/or
      megakaryocytic background, (K562-F8 and TF-1-F8) secrete high levels of FVIII in
      the order of 76.4 and 41.6 ng FVIII:C/ml, whereas moderate and low levels are
      observed in B lymphoblastoid Raji-F8 cells and the T leukemia line Jurkat-F8
      which secrete 6.73 and 1.83 ng FVIII:C/ml, respectively. The capacity to secrete
      rFVIII appeared to depend on factors related to the cell lineage rather than on
      the transduction efficacy. Stimulation of transduced cells with the protein
      kinase C (PKC)-activator phorbol myristate acetate (PMA) resulted in a marked
      augmentation of rFVIII secretion and enhanced green fluorescent protein (EGFP).
      Incubation with 0.1 and 1 ng/ml PMA resulted in up to 2.7-fold (K562-F8, Raji-F8)
      and 1.8-fold (293T-F8) increased rFVIII secretion. The established cell lines
      should be helpful in further elucidating mechanisms that are able to improve
      FVIII secretion in hematopoietic cells on a post-translational level and suggest
      reanalysis of hematopoietic cells as target for gene therapy of hemophilia.

PMID- 12201959
TI  - Second mobilization and collection of peripheral blood progenitor cells in
      healthy donors is associated with lower CD34(+) cell yields.
AB  - We have retrospectively evaluated the results of two cycles of mobilization and
      collection of peripheral blood progenitor cells (PBPC) from 46 healthy donors
      included in the Spanish National Donor Registry. Mobilization involved the
      administration of granulocyte colony-stimulating factor (G-CSF) at a median dose
      of 10 microg/kg per day, and apheresis was begun after the fourth dose of G-CSF
      in both cycles. The median interval between both mobilizations was 187 days
      (range, 7-1428 days). The incidence and types of side-effects were similar after
      both donations, with 25 and 26 donors developing some toxicity after the first
      and second donations, respectively. The median number of CD34(+) cells collected
      was higher after the first mobilization than after the second (5.15 versus 3.16 x
      10(6)/kg, respectively; p = 0.05), and 29 donors yielded fewer CD34(+) cells
      after the second mobilization (p = 0.018). A lower proportion of donors yielded
      CD34(+) cell counts >4 x 10(6)/kg after the second cycle than after the first
      (52% versus 76%, respectively; p = 0.057). Our study shows that second rounds of
      PBPC collection from normal donors are well tolerated but are associated with a
      significantly reduced number of CD34(+) cells collected when the same
      mobilization scheme is used.

PMID- 12201960
TI  - Strong public support for treatment and research using fetal tissue, particularly
      among those accepting the scientific world-view.
AB  - Data from four large representative national sample surveys in Australia between
      1993 and 2000 show strong public support for treatment using fetal tissue.
      Support remains high even if the treatment has only a remote chance of success,
      or if the goal is research rather than treatment. Regression analysis reveals
      striking new evidence on the links between science and moral beliefs. Even
      adjusting for religious denomination and numerous demographic characteristics,
      acceptance of evolution and of aspects of astronomy suggesting that life on earth
      is not unique greatly increases support for using fetal tissue. So does trust in
      scientists.

PMID- 12201961
TI  - Factors affecting purification of CD34(+) peripheral blood stem cells using the
      Baxter Isolex 300i.
AB  - A total of 201 patients with breast cancer, ovarian cancer, or hematological
      malignancies underwent mobilization of peripheral blood stem cells (PBSC) using
      chemotherapy and granulocyte-colony stimulating factor (G-CSF). Stem cell
      products were collected using the Baxter CS3000 pheresis machine. The Baxter
      Isolex 300i was used to perform 240 CD34(+) cell separations on the apheresis
      products. Factors affecting yield and purity of the CD34(+) cells were analyzed.
      Overall yield was 55% and overall purity was 91.7%. T cell contamination was
      limited to 0.43% of total cells. Variables including red blood cells (RBC)
      concentration, platelet concentration, CD34(+) cell concentration, total WBCs
      selected, and time until processing had little effect on yields and purities.
      Installation of version 2.5 of the software in the Isolex 300i showed a modest
      improvement in yield and purity. Patients were reinfused with the cryopreserved
      CD34(+) selected cells following high-dose chemotherapy. No infusion-related side
      effects were noted. Analysis of engraftment data using the CD34(+)-selected cells
      revealed an increased risk of delayed or failed platelet engraftment when <5.0 x
      10(6) CD34(+) cells per kilogram were transplanted. The Baxter Isolex 300i
      provides reproducible CD34(+) cell purification over a wide range of starting
      conditions. To provide prompt engraftment, >5.0 x 10(6) CD34(+) cells per
      kilogram should be infused for transplantation.

PMID- 12201962
TI  - In vivo T cell depletion with low-dose rabbit antithymocyte globulin results in
      low transplant-related mortality and low relapse incidence following unrelated
      hematopoietic stem cell transplantation.
AB  - Stem cell transplantation from unrelated donors is associated with an increased
      risk of graft failure and graft-versus-host disease (GVHD). Addition of
      pretransplant antithymocyte globulin (ATG), although reducing the risk of graft
      rejection and GVHD, bears the risk of overimmunosuppression, resulting in an
      increased relapse rate and transplant-related mortality. Therefore, we evaluated
      in 21 consecutive patients receiving unrelated stem cell grafts from either HLA
      matched (38%) or -mismatched (62%) donors whether low-dose rabbit ATG added to
      cyclosporin A and methotrexate at a total dose of 3.5 mg/kg for HLA-identical and
      5.0 mg/kg for HLA-mismatched transplants given in two divided doses on days -2
      and -1 provides sufficient immunosuppression for prevention of GVHD and graft
      rejection but is associated with an acceptable risk of relapse and transplant
      related mortality. Stable leukocyte engraftment was achieved in all patients
      (100%). Overall survival after a median follow-up of 26 (median, range 14-42)
      months was 56 +/- 26% (95% confidence interval, CI) and the overall relapse rate
      at 3 years was 24 +/- 21%. Three-year survival for standard-risk patients, i.e.,
      chronic myeloid leukemia (CML) in first chronic phase or acute leukemia in first
      complete remission, was 87% +/- 13% versus 40% +/- 31% for patients with more
      advanced disease. The incidence of acute GVHD II-IV degrees was 55 +/- 22%; that
      of severe acute GVHD III-IV degrees was 21 +/- 19%. Chronic GVHD was observed in
      5/17 (29%) patients surviving more than 100 days post stem cell transplantation.
      Transplant-related mortality was 16 +/- 15% (95% CI) at day + 100 and 25 +/- 19%
      (95% CI) at 1 year after the transplant. The data presented show that
      pretransplant in vivo T cell depletion with low-dose rabbit ATG results in a low
      transplant-related mortality due to a low incidence of severe acute and chronic
      GVHD and a low relapse rate. To find out the optimal rabbit ATG dose in the
      unrelated stem cell transplantation setting, further dose-finding studies
      comparing high- and low-dose regimens are necessary.

PMID- 12201963
TI  - Coagulation affects vasculogenesis and angiogenesis: does it affect the
      development of the heart?

PMID- 12201964
TI  - Expansion of PCI at the expense of bypass surgery jeopardizes protection against
      premature death.

PMID- 12201965
TI  - Percutaneous coronary intervention or thrombolytics in ST-elevation infarction.
      What is the emperor really wearing?

PMID- 12201966
TI  - Molecular medicine for the cardiac surgeon.

PMID- 12201967
TI  - Five-year mortality for stable angina in a medical practice study and a
      randomized trial.
AB  - OBJECTIVE: Evolution of revascularization and medical therapy has increased the
      probability of improved survival in patients with stable angina. The present
      investigation tests the hypothesis that medical practice will generate lower
      mortality than randomly assigned bypass surgery in the European Coronary Surgery
      Study (ECSS) two decades earlier. METHOD: Using eligibility criteria of ECSS, a
      clinical decision strategy (CDS) cohort of 362 patients was selected from a
      nationwide study of medical practice in Sweden. Access to the individual data
      allowed common protocol design to compare 5-year mortality between CDS and
      surgical strategy of ECSS. RESULTS AND INTERPRETATION: CDS advised bypass surgery
      (BS) or percutaneous transluminal coronary angioplasty (PTCA) in 93% and medical
      treatment alone in 7%, while 94% of 394 patients randomized to surgery (Euro-S)
      in ECSS obtained BS. Operative mortality was 3.2% for Euro-S while no operative
      deaths occurred in CDS reflecting medical progress during two decades. However,
      the 5-year mortality for CDS decreased first when the risk ratio was adjusted for
      age, diabetes mellitus and hypertension (RR = 0.49 with 95% CI 0.26-0.93) p =
      0.03 suggesting a need for improved comprehensive medical care.

PMID- 12201968
TI  - Establishing primary angioplasty as the preferred treatment for acute myocardial
      infarction.
AB  - OBJECTIVE: To report procedural results and mortality rates from the first 4
      years after establishing primary angioplasty as the preferred treatment for acute
      myocardial infarction in a single Scandinavian centre. DESIGN AND RESULTS: From
      August 1995 to October 1999 all patients with the diagnosis of suspected acute
      myocardial infarction (n = 529, mean age 62 +/- 13 years, 72% men), either
      transferred (73%) or directly admitted to our institution for coronary
      angiography with the intention of performing primary percutaneous coronary
      intervention (primary PCI), were prospectively registered. Procedural success in
      terms of residual stenosis < or = 30% and a final Thrombolysis in Myocardial
      Infarction (TIMI) 3 flow was achieved in 94 and 85% of patients treated,
      respectively. In-hospital delay and procedure times decreased significantly
      during the 4-year study period. A low in-hospital mortality was observed in each
      of the 4 years studied (8.7, 8.7, 7.7 and 6.0%). CONCLUSION: In a centre with
      both directly admitted and transferred patients primary angioplasty can be
      established as the preferred treatment for acute myocardial infarction with an
      initially low complication and mortality rate. During the first years after
      implementing the primary angioplasty programme a learning effect can be
      anticipated with reductions in procedural times.

PMID- 12201969
TI  - Markedly changed age distribution among patients hospitalized for acute
      myocardial infarction.
AB  - OBJECTIVE: To investigate trends in number of hospital admissions due to acute
      myocardial infarction (AMI) in different age groups during the last decade.
      DESIGN: Data on all AMI hospital admissions since 1991 were analysed by gender
      and by age applying 5-year age groups between ages 60 and 90, and < 60 and > or =
      90 as separate groups. RESULTS: From 1991 to 2000 the number of hospital
      admissions for AMI was reduced by 18%. In men, AMI rates decreased in all age
      groups below 80 years and increased in older ages, while in women the
      corresponding breaking point between decreased and increased rates was 85 years.
      In the age group < 80 years, men and women included, the number of AMI admissions
      decreased by 29% (from 11,540 to 8233), while for those > or = 80 there was an
      increase of 25% (from 2917 to 3659). Over the decade the ratio of the numbers of
      AMIs in ages above and below 80 years increased from 0.25 to 0.44. CONCLUSION:
      Over the last decade a striking change in age distribution among AMI patients
      took place, with a marked decrease in age groups below 80 years, as opposed to an
      equally strong increase in the oldest age groups. The development with regard to
      trends for AMI morbidity in society has been more favourable than what appears
      from overall numbers of AMIs.

PMID- 12201970
TI  - Relation of early changes of QT dispersion to changes in left ventricular
      systolic and diastolic function after a first acute myocardial infarction.
AB  - OBJECTIVE: To describe the relation between changes of left ventricular systolic
      and diastolic function and changes of QT dispersion (difference in duration
      between longest and shortest QT interval) following acute myocardial infarction.
      DESIGN: QT dispersion was determined at admission, hospital discharge, and 1 and
      3 months following myocardial infarction in 64 consecutive 1-year survivors.
      Patients were divided into Group A where QT dispersion was < 52 ms at all
      recordings or initially > 52 ms but decreased during follow-up, and Group B where
      QT dispersion remained increased > or = 52 ms at all measurements. Doppler
      Echocardiography was carried out on day 1, day 5, and after 1, 3, and 12 months.
      RESULTS: In 26 patients QT dispersion remained increased > or = 52 ms during the
      first 3 months after infarction. Among these a significant increase of end
      systolic volume was seen whereas low or rapid normalized QT dispersion was
      associated with a significant decrease of ventricular volumes. After 1 year end
      systolic (70 +/- 32 ml vs 49 +/- 16 ml, p = 0.006) and end-diastolic volumes (138
      +/- 41 ml vs 105 +/- 22 ml, p = 0.001) were higher in Group B. In a multivariate
      model Group B was significantly related to an increase of end-diastolic volume (p
      = 0.01). In Group A diastolic function improved in eight patients and in two it
      deteriorated, whereas improvement was seen in one patient and deterioration in
      nine patients from Group B (p < 0.01). CONCLUSION: Following myocardial
      infarction low QT dispersion is associated with preserved left ventricular
      function, whereas persistently increased dispersion is associated with left
      ventricular dilation and deterioration of diastolic function.

PMID- 12201971
TI  - The risk of stroke following coronary revascularization -- a population-based
      long-term follow-up study.
AB  - OBJECTIVE: To study the incidence and risk factors of stroke after coronary
      artery bypass grafting (CABG) or percutaneous transluminal coronary angioplasty
      (PTCA). DESIGN: During 1983-1992, coronary revascularization procedures (n =
      2160) were recorded in patients aged 35-64 years as part of the population-based
      FINMONICA Myocardial Infarction Register. The FINMONICA Stroke Register and
      National Hospital Discharge Register were used to ascertain subsequent stroke
      events in such patients. RESULTS: During the average follow-up of 5.83 years, 155
      patients (7.2%) had a stroke. The cumulative incidence of stroke was 1.55% in the
      first year after revascularization and varied between 0.8 and 1.4% during
      subsequent years. In Cox proportional hazard models the relative risk of stroke
      was 3.01 (p = 0.0007) for a previous stroke, 2.61 (p = 0.0001) for diabetes
      mellitus, 2.15 (p = 0.007) for low income (compared with high income), 2.06 (p =
      0.03) for male sex, and 1.43 (p = 0.02) for a 10-year increment in age.
      CONCLUSION: The incidence of stroke during the first year after revascularization
      was five times higher than among the age- and sex-matched general population.
      Patients with a previous stroke, diabetes mellitus, advanced age, male sex and
      low socioeconomic status need special attention because of increased risk of
      stroke after CABG or PTCA.

PMID- 12201972
TI  - No increase of plasma malondialdehyde after primary coronary angioplasty for
      acute myocardial infarction.
AB  - OBJECTIVE: Free radicals formed after coronary artery occlusion and reperfusion
      are assumed to produce myocardial stunning and possibly other forms of
      reperfusion injury as well. Malondialdehyde (MDA) is an end product in the lipid
      peroxidation chain reaction and is frequently used as a marker for free oxygen
      radical production. Increased levels of plasma MDA have been found following
      successful thrombolytic therapy. The aim of this study was to investigate whether
      plasma MDA levels also increase after successful primary percutaneous
      transluminal coronary angioplasty (PTCA) in acute myocardial infarction (AMI).
      DESIGN: In 23 patients with AMI, treated with primary PTCA, plasma MDA was
      analysed using a high-performance liquid chromatography method (HPLC). The
      results obtained with this method were compared with those obtained with a
      fluorimetric assay of thiobarbituric acid reactive substances (TBARS). This assay
      measures MDA but with a lower specificity. RESULTS: We found a significant
      decrease of plasma MDA from baseline 0.99 to 0.87 micro mol/l at 30 min and to
      0.90 micro mol/l at 90 min following the primary PTCA (p = 0.048 and 0.014,
      respectively). No significant changes in TBARS method levels were observed.
      CONCLUSION: Instead of the expected increase in MDA following reperfusion we
      found a significant decrease. The results from measurements of MDA and TBARS were
      significantly incompatible. The results raise serious doubts as to the usefulness
      of increased plasma levels of MDA as a marker of oxidative stress caused by
      coronary reperfusion in patients treated with angioplasty.

PMID- 12201973
TI  - Use of heparin-bonded circuits in cardiopulmonary bypass improves clinical
      outcome.
AB  - OBJECTIVE: The use of heparin-coated surfaces in cardiopulmonary bypass has been
      shown to decrease the inflammatory response imposed by the contact between blood
      and artificial surfaces. One would expect this reaction to improve clinical
      outcome. However, this has been difficult to verify. This investigation is based
      on an aggregation of two randomized studies from our institution and highlights
      possible effects of heparin coating on a number of clinically oriented
      parameters. DESIGN: Departmental analysis of patients subjected to coronary
      artery bypass surgery using heparin-coated circuits. Cardiopulmonary bypass was
      employed using either the Carmeda or Duraflo heparin coatings compared with a
      control. The systemic heparin dose was reduced in the heparin-coated groups (ACT
      > 250 s) vs control group patients (ACT > 480 s). The effects of heparin coating
      related to clinical outcome were studied. RESULTS: The use of heparin-coated
      circuits reduced the mean length of stay in hospital from 7.8 +/- 2.5 to 7.3 +/-
      1.8 days (p = 0.040) and postoperative ventilation time from 9.7 +/- 9.2 to 8.2
      +/- 8.5 h (p = 0.018), blood loss 8 h post surgery from 676 +/- 385 to 540 +/-
      245 ml (p = 0.001), individual perioperative change of haemoglobin loss (p =
      0.001), leukocyte count (p = 0.000) and creatinine elevation (p = 0.000),
      proportion of patients exposed to allogenous blood transfusions 39.2 vs 23.9% (p
      = 0.001), postoperative coagulation disturbances 4.4 vs 0.4% (p = 0.006),
      postoperative deviations from the normal postoperative course 47.2 vs 36.7% (p =
      0.035), neurological deviations 9.4 vs 3.9% (p = 0.021) and atrial fibrillation
      26.4 vs 18.0% (p = 0.041). No effects were found with respect to perioperative
      platelet count, postoperative fever reaction and 5-year survival. CONCLUSION:
      Based on several indicators, the use of heparin coating in cardiopulmonary bypass
      is associated with improved clinical results.

PMID- 12201974
TI  - Apoptotic activity is increased in brain cortex infarct after hypothermic
      circulatory arrest in a porcine model.
AB  - OBJECTIVE: It has been shown that apoptosis contributes to neuronal cell death
      after ischemia, and we evaluated the degree of apoptotic activity occurring in
      brain cortex of pigs after hypothermic circulatory arrest (HCA). DESIGN: Thirty
      one pigs underwent 75 min of HCA at 20 degrees C. Histological examination of the
      brain was performed, and slides of brain cortex were evaluated for apoptotic
      activity by the TUNEL method. RESULTS: Ten animals died during the first
      postoperative day and 21 survived until the seventh postoperative day. Brain
      cortex infarcts were found in animals that survived 7 days and these were
      included in this study. The median histopathological score among animals that
      died on the first postoperative day was 3.0 (range, 2-4), whereas it was 4.0
      (range, 2-4) among survivors (p = 0.019). The apoptotic index was particularly
      high in the area of the infarct, whereas only a few TUNEL-stained cells were
      observed in noninfarcted areas. The apoptotic index was nil in all pigs that died
      in the first postoperative period, whereas it was 2.0 (range, 0-6) among the
      animals that survived until the seventh postoperative day (p < 0.0001).
      CONCLUSION: The apoptotic index was significantly increased in brain cortex
      infarcts of animals that survived 7 days after HCA, whereas only a few apoptotic
      cells were observed in noninfarcted areas of these animals as well as in animals
      that died on the first postoperative day. Further studies are required to
      elucidate the timing of development of brain infarction after HCA and whether
      neuroprotective strategies targeting the apoptotic process may mitigate brain
      damage.

PMID- 12201975
TI  - Delirium after coronary bypass surgery evaluated by the organic brain syndrome
      protocol.
AB  - OBJECTIVE: The aim was to evaluate symptoms of delirium from a psychogeriatric
      perspective occurring postoperative to coronary bypass surgery. DESIGN: Patients,
      > or = 60 years, scheduled for coronary bypass surgery (n = 52) were enrolled in
      a prospective descriptive study. The patients were evaluated before and several
      times after surgery by the Organic Brain Syndrome scale, and delirium was
      diagnosed according to psychiatric codes. RESULTS: Of the 52 patients, 23%
      presented delirium. These patients were older than the control group, 73.5 +/-
      4.2 and 69.3 +/- 5.9 years, respectively (mean +/- SD, p < 0.01), and had more
      frequently a history of previous stroke (p < 0.05). Emotional delirium was seen
      in 83%, hyperactive delirium in about 40%, and 25% were classified to have a
      psychotic delirium. A major finding was a 58% frequency of hallucinations and
      illusions among patients with delirium, and a similar rate among those without
      delirium. CONCLUSION: Delirium is common after cardiac surgery in particular in
      older patients, but is often under-diagnosed. Hallucinations were common in both
      delirious and non-delirious patients.

PMID- 12201976
TI  - Inferential processing and story recall in children with communication problems:
      a comparison of specific language impairment, pragmatic language impairment and
      high-functioning autism.
AB  - An investigation is reported into the story comprehension abilities of four
      groups of children: those with typical specific language impairment (SLI-T),
      those with pragmatic language impairments who were not autistic (PLI), those with
      high-functioning autism (HFA) and typically developing controls. The story
      comprehension task required children to answer questions about the literal
      content of the story, as well as questions involving two types of inferences:
      text-connecting and gap-filling. The control children outscored the three
      clinical groups on story comprehension, but the group means of the clinical
      groups did not differ. However, categorical examination of the data revealed that
      children with pragmatic difficulties related to HFA were more likely to have
      specific inferencing deficits. Error analysis suggested that all children could
      make inferences, but these were not always relevant to the story context. This
      supports the notion of weak central coherence underlying deficits in inferencing.
      There were no group differences on story recall. However, there was a strong
      relationship between story comprehension and recall, in that those who had better
      comprehension tended to have better recall. It is concluded that comprehension
      aids recall by enabling the listener to build a more stable mental representation
      of the story. The pragmatic deficits seen in autism compromise this process.

PMID- 12201977
TI  - Children's grammatical categories of verb and noun: a comparative look at
      children with specific language impairment (SLI) and normal language (NL).
AB  - The study investigated the development of grammatical categories (noun and verb)
      in young language learners. Twenty-eight children with specific language
      impairment (SLI) with a mean language age of 35 months and 28 children with
      normal language (NL) with a mean language age of 34 months were exposed to four
      novel verbs and four novel nouns during 10 experimental child-directed play
      sessions. The lexical items were modelled with four experimentally controlled
      argument structures. Both groups of children showed little productivity with
      syntactic marking of arguments in the novel verb conditions. Thus, both groups of
      children mostly followed the surface structure of the model presented to them,
      regardless of the argument they were trying to express. Therefore, there was
      little evidence of verb-general processes. In contrast, both groups used nouns in
      semantic roles that had not been modelled for them. Importantly, however,
      children with SLI still appeared to be more input dependent than NL children.
      This suggests that children with NL were working with a robust noun schema,
      whereas children with SLI were not. Taken together, the findings suggest that
      neither group of children had a grammatical category of verb, but demonstrated a
      general knowledge of the grammatical category of noun. These findings are
      discussed in relation to current theories of normal and impaired language
      development.

PMID- 12201978
TI  - Speech and language therapy services to education in England and Wales.
AB  - Services for children with speech and language needs in England and Wales are in
      a period of change. The context is subject to major systemic pressures deriving
      from government policies. These include the development of inclusive education
      and encouragement of multiprofessional collaboration in policy development and
      practice ('joined up thinking'). In addition, structures at local level are
      changing with the establishment of unitary authorities and the change from Health
      Trusts to Primary Care Trusts. Professional practice is also changing with a
      shift from clinical to community settings for speech and language therapists
      working with children. The present study reports on a survey sponsored by the
      Department for Education and Employment, Department of Health and the Welsh
      Assembly to identify the nature of speech and language therapy (SLT) services
      provided to education in England and Wales. The sample comprised all SLT service
      managers (n = 133, response rate 74%). The results indicate that services vary
      greatly in size and in their SLT: child ratio, with a mean of one SLT to 4257
      child population. The caseload was highest for the 5-10 age group, and service
      delivery was targeted at these children, with low levels of work with secondary
      aged pupils. Most provision in educational settings was made to mainstream
      schools, but the provision of SLT time per child was substantially higher in
      specialist language resources. Apart from the preschool phase, most SLT provision
      was for children with statements of special educational needs. Prioritization of
      service delivery was usually by severity of need. The provision of bilingual SLT
      services was very limited, with only 14.0 full-time equivalents SLTs fluent in a
      community language, other than Welsh, where proportionately availability was much
      greater. Most LEAs funded SLT posts, although these were usually employed as part
      of the SLT service, with only about 10% of LEAs employing SLTs direct. However,
      55.5% of SLT managers reported that recruitment and retention were problematic,
      resulting in gaps in the service. These findings are discussed with respect to
      changes driven by professional judgements on the nature of optimal service
      delivery, and government policy, with particular reference to inclusion and
      equity of service delivery.

PMID- 12201979
TI  - Phonological training in children with dyslexia using temporally modified speech:
      a three-step pilot investigation.
AB  - Three separate studies were successively carried out to investigate the
      usefulness of intensively training children with dyslexia with daily exercizes
      based on the temporal processing theory of dyslexia, according to which these
      children would be specifically unable to process brief and rapidly changing
      auditory stimuli. The speech modification, similar for the three studies, was
      close to that proposed by Merzenich et al. (1996) and Tallal et al. (1996),
      including both artificial slowing of natural speech stimuli and amplification of
      brief, unstable portions of the speech signal. In the first study, 12 children,
      aged 10-12 years, received either such modified speech or normal speech for 1 h a
      day, 5 days a week, over 5 weeks, and they were assessed on phonological tasks
      before, during and after training. A significant advantage for the modified
      speech group was found both in pre-post-training improvement and in day-to-day
      progression on phonological performance. In a second study, 29 children with
      dyslexia, aged 5-12, received a similar training, but for only 15 min a day, 7
      days a week, over 6 weeks, part at the speech therapist office, part in their own
      homes. The finding of comparable improvement in a more 'natural' environment and
      in children over a wider age range indicates both the efficacy and feasibility of
      the method in usual clinical practice. However, this study also showed that one
      of four children did not improve as expected, prompting a third study where 23
      other children underwent specific tasks presumably exploring various aspects of
      temporal processing in order to find predictors of training efficacy. A 'temporal
      order judgement' (TOJ) task was found best correlated with post-training
      improvement, suggesting that one use this task for selecting the best candidates
      for temporo-phonological training. Moreover, such correlation provided further
      argument in favour of the temporal deficit theory of dyslexia, not only by
      showing a link between a purely temporal task and ultimate phonological
      performance, but also by demonstrating that TOJ performance itself improves after
      phonological training. Finally, and taken together, these studies provide further
      justification for a rational, indication-based temporo-phonological treatment of
      dyslexia. Possible neural substrates of the relevant mechanisms are discussed in
      the light of recent experimental and brain-imaging studies.

PMID- 12201980
TI  - Strategies for achieving joint attention when signing to children with Down's
      syndrome.
AB  - Research indicates that joint attention is an important factor in determining the
      rate and nature of early vocabulary development in typically developing children.
      Studies conducted with deaf children acquiring sign language indicate that
      caregivers adopt special strategies for achieving joint attention with this
      group: these strategies make allowance for the visual medium in which the
      language is transmitted. Joint attention is also important for the development of
      communication in children with Down's syndrome, who also often have restricted
      attentional capacity. Moreover, there is good evidence that the use of signed
      input in addition to speech can have significant benefits for these children.
      This paper reports on a study designed to explore the utility of strategies
      observed in deaf parents for the achievement of joint attention when signing with
      children with Down's syndrome. Data are presented from recordings of four
      children with Down's syndrome and their mothers. The results showed that the
      mothers were successful in enabling the child to perceive both signed input and
      contextual referents much of the time, but that the range of strategies used was
      very limited compared to deaf parents of deaf children. Adopting a wider range of
      strategies would allow a considerable increase in signed input. Implications for
      intervention programmes are discussed.

PMID- 12201981
TI  - Speech and language skills and cognitive functioning in children with Apert
      syndrome: a pilot study.
AB  - There are few studies that report findings on the speech and language
      characteristics of Apert syndrome and little is known about the cognitive profile
      of the syndrome. The current study addresses this gap and explores speech,
      language, resonance/voice, attention oro-motor and cognitive skills in a group of
      10 children (4;1-5;11) with Apert syndrome. The speech and language battery
      included: the CELF-Pre-school, the PLS-3, the Vocal Profile Analysis, GOS.SP.ASS,
      PACS; and the Brodsky Drooling Scale. Subscales of the BAS II-Early Years Version
      were used to assess cognition. Data were also collected on other factors that
      could influence developmental outcome such as audiological history and
      management; occlusion/dentition; respiratory problems and management;
      neuroanatomical abnormalities; the number and nature of cranial surgeries; and
      the occurrence of raised intracranial pressure. All children for whom a
      Performance IQ was obtained (n = 8) had abilities within the average range and IQ
      scores were considerably higher than those reported in previous studies. Eight
      children had moderate or severe language difficulties and expressive language
      difficulties were the most frequent. These language difficulties were not
      associated with a general cognitive deficit. All the children had problems with
      attention, speech and oro-motor skills. Nine had abnormal voice. In addition, a
      range of other associated factors that could affect functioning were identified.
      The discrepancies between the current study and previous investigations are
      outlined. Parameters for assessment are considered. The implications of these
      findings for valid assessments of children with Apert syndrome are discussed.
      Multidisciplinary assessment of children with Apert syndrome across a broad range
      of dimensions is recommended to obtain a profile of each child's strengths and
      weaknesses to ensure that appropriate educational placements and early
      interventions are implemented. Considering patterns of development over time at
      key ages is also argued to be of central importance.

PMID- 12201982
TI  - Carer knowledge of dysphagia management strategies.
AB  - Dysphagia can have many negative health consequences for people with learning
      disabilities, including dehydration, aspiration and asphyxiation. Few studies
      have investigated dysphagia management among adults with learning disabilities.
      This study aims to contribute to the existing knowledge by investigating carer
      knowledge of speech and language therapists' (SLTs) recommendations regarding
      dysphagia management, and by comparing carer knowledge with their behavioural
      adherence to SLT recommendations. An exploratory study was undertaken
      investigating carer knowledge of dysphagia management strategies, along with a
      within-participants' study comparing carer knowledge and adherence. Structured
      interviews were conducted with carers supporting adults with learning
      disabilities and dysphagia to explore and ascertain their knowledge of dysphagia
      management. These data were then compared with observational data gathered in
      naturalistic contexts, assessing the behavioural adherence of these same carers.
      Recommendations pertaining to altering consistency and using specialized
      equipment and utensils were recalled significantly more readily than those
      concerning support and prompting for the dysphagic persons. Moreover, carers
      adhered to management strategies to a significantly greater degree than they
      could recall the details of the written guidelines containing the dysphagia
      management strategies. The findings suggest that tangible and routinely used
      management strategies, e.g. food and drink consistency, and use of specialized
      utensils, are easier for carers to adhere to and remember than support-based
      strategies such as verbal prompting and pacing. The discrepancy between
      compliance and knowledge can be explained by calling upon cognitive theories of
      memory and skill acquisition. This has implications for the selection of relevant
      outcomes of dysphagia training of direct care staff. Knowledge does not
      necessarily predict actual behavioural adherence and, though desirable, does not
      appear to be an adequate outcome indicator if the goal is behavioural adherence.
      Practice implications for SLTs training carers in dysphagia management strategies
      include combating fossilization of incorrect knowledge; encouraging carers to
      refamiliarize themselves with management strategies and their rationales
      periodically following initial training; and providing more specific contingency
      information for support and prompting in the guideline documentation.

PMID- 12201983
TI  - Ethics and interprofessional care.

PMID- 12201984
TI  - Interprofessionalism and ethics: consensus or clash of cultures?
AB  - The ethical arguments which underpin the call for interdisciplinary collaboration
      are analysed. In particular, the concept of 'teamwork' is considered as well as
      the organisational, professional, personal and cultural obstacles that constitute
      the barriers to the effective development of interdisciplinary relationships.

PMID- 12201985
TI  - Treatment, custody, support: an exploratory qualitative dialogue to map the
      ethics of interagency co-operation in hospital emergency departments in the UK
      and the Netherlands.
AB  - Interviews with senior professionals in accident and emergency (A&E) healthcare,
      policing and social services to map the ethical dimensions of interagency
      collaboration suggest that the main ethical themes for systematic research are
      information sharing and confidentiality, consent, professional values and
      autonomy, human rights, formal (organisational) accountability, staff safety and
      public interest collaboration. An emerging specific issue is the extent of A&E
      disclosure to the police and to the social services and its legal and ethical
      parameters.

PMID- 12201986
TI  - Ethics and managed care.
AB  - Managed care in the USA is best understood in the context of the history of
      health care. It is an effort to manage the soaring costs of health care while
      retaining quality. Many ethical concerns arise because managed care organizations
      (MCOs) have dual purposes: to realize profits and to provide quality care.
      Dilemmas are created when persons in institutions are expected to play
      conflicting roles or when professionals, patients, or others in MCOs lose their
      voices as participating persons. These and other ethical concerns can be
      addressed by on-going processes of involvement of persons who have a stake in
      these organizational arrangements.

PMID- 12201987
TI  - Ethical dilemmas in charging for care: contrasting the views of social work and
      legal professionals.
AB  - This article draws on the findings of a recent study funded by the Nuffield
      Foundation. The study explored attitudes, practices and policy in relation to
      charging and assessing older people who were considering entering residential and
      nursing home care. In five differing local authorities, a sample of social
      services practitioners (care managers) completed a postal questionnaire and
      interviews were held at a number of levels with staff. At the same time,
      independent legal practitioners in these areas, who are involved in advising
      older people, were surveyed and a small number of individual practitioners were
      interviewed. The focus of this article is on contrasting the attitudes and views
      of care managers and legal practitioners towards their work in relation to older
      people, finances and charging for long-term care. In particular, there will be an
      emphasis on the ethical dilemmas identified by the respondents from the different
      professions involved in the study.

PMID- 12201988
TI  - Commitment to health: a shared ethical bond between professions.
AB  - It is commonly assumed that Codes of Ethics are supported by concrete ethical
      principles, that adherence to Codes of Ethics guarantees ethical behaviour and
      that there is widespread agreement about ethical standards. Each of these
      assumptions is false. Codes of Ethics are inevitably open to wide interpretation,
      and it is impossible to demonstrate absolute moral standards. Health and social
      care workers should not adhere to unexplained 'ethical principles' insufficient
      to guide practical decision making. Anyone who recognises that all human actions
      potentially have ethical content may choose to make an ethical commitment. In
      order to work for health, health workers ought to commit to a substantial theory
      of health. One such theory--the foundations theory of health--is briefly
      explained and illustrated. The foundations theory can form a shared ethical bond
      between health and social care professionals, since both professions regularly
      strive to achieve foundational health for their patients and clients.

PMID- 12201990
TI  - Supervision: the process of life-long learning in social and educational
      professions.
AB  - The supervision process represents one of the possible processes of life-long
      learning and development of an adult. This paper presents a developmental
      educational model of supervision. It is a specific learning developmental and
      supportive method of professional reflection and counselling used in social and
      educational settings in Slovenia. Different concepts that explain learning and
      acquiring competence in the process of supervision are discussed. Special
      emphasis is given to the process of experiential learning (Kolb), learning within
      the zone of proximal development (Vygotsky) and the process of mental adaptation
      leading to new cognition (Piaget).

PMID- 12201991
TI  - Portrait of social work.
AB  - Social work is concerned with enhancing the well-being of people within their
      social contexts. It is a broad profession with diverse practices. These range
      from a focus on the personal distress of individuals to the collective
      arrangements and social processes that influence the well-being of groups and
      communities. The unique contribution of social work to the caring professions is
      its broad contextualised approach to addressing human needs. Yet this breadth of
      scope also provides fertile ground for competing discourses within the
      profession. This paper provides an overview of the 'highly contested' nature of
      social work's goals, theories and methods of practice.

PMID- 12201992
TI  - 'Walking in the moccasins...'. Extending the boundaries of undergraduate medical
      education.

PMID- 12201993
TI  - Composition options for tissue-engineered bone.
AB  - The logical assembly of tissue-engineered bone is ultimately directed by the
      clinical status of the patient. The basic elements for tissue-engineered bone
      should include signaling molecules, cells, and extracellular matrix. The assembly
      of these basic elements may need to be modified by tissue engineers to account
      for patient variables of age, gender, health, systemic conditions, habits, and
      anatomical implant. Moreover, different regions of the body will have different
      functional loads and vascularity. This review discusses several basic options
      that may be necessary to engineer bone, including spatial and temporal assembly
      of signaling factors, cells, and biomimetic extracellular matrices. Moreover, the
      importance of the health care status of the patient who may be receiving the
      tissue-engineered composition is emphasized.

PMID- 12201994
TI  - Derivation of type II alveolar epithelial cells from murine embryonic stem cells.
AB  - Embryonic stem (ES) cell pluripotency is being investigated increasingly to
      obtain specific cell lineages for tissue engineering. However, the possibility
      that ES cells can give rise to lung tissue has not been tested. We hypothesized
      that lung epithelial cells (type II pneumocytes) can be derived in vitro from
      murine ES cells. After withdrawal of leukemia inhibitory factor (LIF) and
      formation of embryoid bodies in maintenance medium for 10, 20, and 30 days,
      differentiating ES cells were kept in the same medium or transferred to serum
      free small airway growth medium (SAGM) for a further 3 or 14 days of culture. The
      presence of type II pneumocytes in the resulting mixed cultures was demonstrated
      by reverse transcriptase-polymerase chain reaction (RT-PCR) of surfactant protein
      C (SPC) mRNA, immunostaining of SPC, and electron microscopy of osmiophilic
      lamellar bodies only at 30 days sampling time. SAGM appeared to be more favorable
      for type II cell formation than ES medium. No SPC transcripts were found in
      differentiating cells grown under the same conditions without formation of
      embryoid bodies. These findings could form the basis for the enrichment of ES
      cell-derived cultures with type II pneumocytes, and provide an in vitro system
      for investigating mechanisms of lung repair and regeneration.

PMID- 12201995
TI  - Differentiating embryonic stem cells: GAPDH, but neither HPRT nor beta-tubulin is
      suitable as an internal standard for measuring RNA levels.
AB  - Embryonic stem (ES) cells are pluripotent cell lines that possess virtually
      unlimited self-renewal and differentiation capacity. Such characteristics make
      them potentially an invaluable cell source for diverse tissue-engineering
      applications. In vitro ES cell differentiation occurs spontaneously in three
      dimensional structures termed "embryoid bodies" that mimic postimplantation
      embryonic tissue. HPRT, beta-tubulin, and GAPDH are commonly used as internal RNA
      standards in ES cell-derived gene transcription studies so that corrected sample
      mRNA levels can be obtained for (semi) quantitative gene expression data.
      However, if reliable data is to be obtained, it is essential that such
      housekeeping gene expression remains constant, and this has not been demonstrated
      for differentiating ES cell cultures, which represent a mixed and changing
      population of cells with time in culture. Therefore, in the present study, we
      tested the suitability of these housekeeping genes to act as true internal
      standards for differentiating murine ES cells cultured as embryoid bodies. PCR
      amplified gene-specific products were quantified from digital images of ethidium
      bromide-stained gels using a computer software package. Both HPRT and beta
      tubulin mRNA levels varied markedly in spontaneously differentiating and growth
      factor-supplemented (TGF-beta) ES cell cultures (p < 0.001, ANOVA), while GAPDH
      expression remained relatively constant (p > 0.2). Our results demonstrate the
      importance of fully validating housekeeping gene expression in in vitro ES cell
      gene transcription studies and suggest that GAPDH may be a suitable candidate to
      act as an internal RNA standard, while both HPRT and beta-tubulin appear to be
      inappropriate. Finally, we demonstrate enhanced mesodermal differentiation of ES
      cell-derived cultures by treatment with TGF-beta through significant upregulation
      of Brachyury T expression, with a concomitant decrease in expression of the
      undifferentiated ES cell marker Oct-4.

PMID- 12201996
TI  - Effects of hedgehog proteins on tissue engineering of cartilage in vitro.
AB  - The effects of three derivatives of the N-terminal signaling domain of hedgehog
      proteins on cartilage engineered in vitro were investigated, with specific focus
      on the ability to increase tissue growth rate and concentrations of major
      extracellular matrix components, that is, glycosaminoglycans (GAG) and collagen,
      and on the effects on morphological appearance of the tissue. Bovine articular
      chondrocytes were cultured on biodegradable polyglycolic acid (PGA) scaffolds
      with or without the addition of dipalmitoylated sonic hedgehog (dp-shh),
      dipalmitoylated indian hedgehog (dp-ihh), or sonic hedgehog dimer (shh-dimer) to
      medium with either 1% or 10% fetal bovine serum (FBS). All three hedgehog
      proteins dose-dependently increased construct weights (by up to 1.95-fold, dp-shh
      at 1,000 ng/mL) and the fraction of GAG over 4 weeks (by up to 2.7-fold, dp-shh
      at 1,000 ng/mL), as compared to control constructs. Dp-shh and dp-ihh elicited
      similar responses; a 10-fold higher concentration of nonacylated shh-dimer was
      necessary to reach comparable results. Positive hedgehog effects were more
      pronounced in medium containing 1% FBS than in medium containing 10% FBS;
      however, at either FBS concentration, cartilaginous tissues grown in the presence
      of hedgehog proteins appeared morphologically more mature. Hedgehog derivatives
      thus appear as promising candidates to improve the development and composition of
      engineered cartilage.

PMID- 12201997
TI  - Serum-free medium supplemented with high-concentration FGF2 for cell expansion
      culture of human ear chondrocytes promotes redifferentiation capacity.
AB  - For tissue engineering of autologous cartilage, cell expansion is needed to
      obtain the cell numbers required. Standard expansion media contain bovine serum.
      This has several disadvantages, that is, the risk of transmitting diseases and
      serum-batch variations. The aim of this study was to find a serum-free medium
      with at least the same potential to expand cell numbers as serum-containing
      media. Ear chondrocytes of three young children were expanded in either serum
      containing medium (SCM; DMEM with 10% fetal calf serum) or serum-free medium
      (SFM; DMEM with ITS+) supplemented with 5 or 100 ng/mL fibroblast growth factor-2
      (FGF2). To promote cell adherence onto the culture flask, the serum-free
      conditions were cultured with 10% serum for 1 day after each trypsinization.
      After the fourth passage, the chondrocytes were encapsuled in alginate beads and
      redifferentiated in a SFM (DMEM with ITS+, hydrocortisone, and L-ascorbic acid)
      supplemented with 10 ng/mL IGF-I and 10 ng/mL TGFbeta-2. Results showed that
      expansion in SFM with 100 ng/mL FGF2 was comparable to expansion in SCM.
      Redifferentiation with SFM with IGF-I and TGFbeta-2 showed high collagen type II
      expression and high GAG/DNA production regardless of which expansion medium had
      been used. However, chondrocytes expanded in SFM with 100 ng/mL FGF2 resulted in
      less positive cells for collagen type I and 11-fibrau (a fibroblast membrane
      marker). The present study shows that it is possible to use serum-free medium for
      tissue engineering of cartilage. Expansion of immature ear chondrocytes in SFM
      supplemented with high-concentration FGF2 resulted in high cell numbers, which in
      addition had better redifferentiation capacity than cells expanded in medium with
      10% serum.

PMID- 12201998
TI  - Fluid-induced shear stress stimulates chondrocyte proliferation partially
      mediated via TGF-beta1.
AB  - There is growing evidence that a hydrodynamic environment is beneficial for
      growing cartilage tissue-engineered constructs; however, the mechanisms by which
      fluid shear provides for a better construct are not well understood. In this
      study, we investigated one possible mechanism by which constructs grow faster
      under fluid shear: fluid shear upregulates chondrocyte proliferation. Further, we
      investigated if this effect is mediated by TGF-beta1, a known mediator of fluid
      shear effects in other cell types and a mitogen for chondrocytes. To test the
      hypotheses, primary bovine articular chondrocytes were cultured in monolayers
      (approximately 40,000 cells/cm(2)) to 80-85% confluency. After 24 h of growth
      arrest, cells were exposed to 3.5 Pa fluid shear stress for 96 h. Total DNA was
      compared between flow and static culture slides. Total TGF-beta1 was quantified
      in flow-conditioned media (CM) and static culture-CM. Mitogenic capacity of the
      CM, with or without anti-TGF-beta1 or anti-TbetaRII (TGF beta receptor type II)
      antibodies, was also assessed. Results show that fluid shear significantly up
      regulates chondrocyte proliferation (p < 0.02). Further, total TGF-beta1 in the
      flow-CM was more than 3.5-fold higher (p < 0.03) and its mitogenicity
      significantly higher (p < 0.007) as compared to static culture-CM. Adding excess
      anti-TGF-beta1 or anti-TbetaRII antibodies partially, but significantly depressed
      mitogenicity (approximately 20% decrease) of the flow-CM. These results show that
      fluid shear stress upregulates chondrocyte proliferation and that this effect is
      partially mediated by TGF-beta1.

PMID- 12201999
TI  - Bone morphogenetic proteins-2, -12, and -13 modulate in vitro development of
      engineered cartilage.
AB  - Bovine calf articular chondrocytes were seeded onto biodegradable polyglycolic
      acid (PGA) scaffolds and cultured in either control medium or medium supplemented
      with 1, 10, or 100 ng/mL of bone morphogenetic proteins (BMPs) BMP-2, BMP-12, or
      BMP-13. Under all conditions investigated, cell-polymer constructs cultivated for
      4 weeks in vitro macroscopically and histologically resembled native cartilage.
      Addition of 100 ng/mL of BMP-2, BMP-12, or BMP-13 increased the total mass of the
      constructs relative to the controls by 121%, 80%, and 62%, respectively, which
      was accompanied by increases in the absolute amounts of collagen,
      glycosaminoglycans (GAG), and cells. The addition of 100 ng/mL of BMP-2, BMP-12,
      or BMP-13 increased the weight percentage of GAG in the constructs by 27%, 18%,
      and 15%, and decreased the weight percent of total collagen to 63%, 89%, and 83%
      of controls, respectively. BMP-2, but not BMP-12 or BMP-13 promoted chondrocyte
      hypertrophy. Taken together, these data suggest that BMP-2, BMP-12, and BMP-13
      increase growth rate and modulate the composition of engineered cartilage and
      that 100 ng/mL of BMP-2 has the greatest effect. In addition, in vitro engineered
      cartilage provides a system for studying the effects of BMPs on chondrogenesis in
      a well-defined environment.

PMID- 12202000
TI  - Time course of de novo adipogenesis in matrigel by gelatin microspheres
      incorporating basic fibroblast growth factor.
AB  - Controlled release of basic fibroblast growth factor (bFGF) from gelatin
      microspheres achieved de novo adipogenesis at the implanted site of a basement
      membrane extract (Matrigel). Following subcutaneous co-implantation of Matrigel
      and gelatin microspheres incorporating 0.1 microg of bFGF into the back of mice,
      adipose tissue was formed at the implanted site after 4 weeks postoperatively
      although the extent increased with implantation time. Formation of adipose tissue
      was significantly faster than the co-implantation of Matrigel, and 0.1 microg of
      free bFGF while a larger volume of the adipose tissue formed was retained 15
      weeks later. When measured in Matrigel co-implanted with the gelatin microspheres
      incorporating bFGF, the number of cells infiltrated into Matrigel increased to a
      significantly high extent compared with the bFGF co-implantation. Matrigel alone
      was much less effective in inducing formation of adipose tissue. We conclude that
      gelatin microspheres incorporating bFGF enable Matrigel to efficiently induce de
      novo adipogenesis at the implanted site in respect to the formation rate and
      volume of adipose tissue.

PMID- 12202001
TI  - Modulation of integrin expression on rat bone marrow cells by substrates with
      different surface characteristics.
AB  - Biomaterials have been shown to be able to influence the growth and
      differentiation of osteogenic cells cultured on the surface. Although the precise
      mechanisms by which the materials influence osteogenic cells are unclear, it is
      possible that the materials manipulate the expression of integrins by the cells.
      We therefore studied the expression of a number of integrins by rat bone marrow
      (RBM) cells, after culture on culture polystyrene, on machined and grit-blasted
      titanium, and on calcium phosphate-coated titanium. Integrin expression was
      studied by FACS analysis. We found a large variation in the expression of
      integrins by cells in replicate experiments. After culture on polystyrene for 7
      days, cells expressed alpha1, alpha2, alpha3, alpha5, alpha6, beta1, and beta3,
      although some of the subunits were expressed only occasionally. The cells did not
      express the alpha4 subunit. After culture of RBM cells for 8 days on coated and
      noncoated titanium substrates, cells always expressed alpha3, alpha5, alpha6, and
      beta1. The alpha1 and beta3 subunits were only expressed in some of the
      experiments. Frequently, the expression of alpha5, alpha6, and beta1 was higher
      on the coated than on the noncoated titanium substrates. Based on our results, we
      conclude that the studied materials are capable of influencing the expression of
      integrins by RBM cells cultured on relevant implant materials.

PMID- 12202002
TI  - The correlation and reproducibility of histological scoring systems in cartilage
      repair.
AB  - In recent years, the field of cartilage tissue engineering has seen a sharp
      increase in publications using many tissue engineering techniques and various
      analysis methods. Comparison between studies remains difficult, due to a lack of
      uniformity in methods used. A broad range of histological scoring systems is used
      to examine cartilage quality. Unfortunately, so far little is known on the
      reliability and correlation of these scoring systems. The objective of this study
      was to compare two frequently used cartilage repair grading scales, namely, the
      comprehensive O'Driscoll and the simple Pineda scale. We determined the intra-
      and interobserver variability of each score as well as the correlation between
      them. Thirty-eight joint section samples with variable cartilage quality were
      examined. Three observers documented their findings with both systems at two
      points in time. Statistical analysis showed very good intra- and interobserver
      reliability as well as a good correlation between the two scores. For the
      intraobserver variability of the O'Driscoll scale, we found an average difference
      of 0.05 with a SD of 0.93 in a 24-point score and a kappavalue of 0.87. For the
      interobserver reliability, the average difference was 0.001, SD 2.25, and a
      kappavalue of 0.92. The Pineda scale showed an average difference of 0.86 with a
      SD of 1.38 in a 14-point score and a kappavalue of 0.86 for the intraobserver
      reliability, whereas values for the interobserver reliability were average
      difference 0.82, SD 0.96, and a kappavalue of 0.89. The comparison between the
      two scales showed a high, inversely related correlation with a correlation
      coefficient of 0.71. From these results, we concluded that both the O'Driscoll
      and the Pineda scales are reliable semiquantitative cartilage scoring systems and
      that acceptance for general use of these two scores will benefit the reliability
      of literature on tissue engineering for cartilage repair. Thus, the added
      strength of comparison between published study results allows better
      understanding of cartilage repair publications and increases the impact of their
      results.

PMID- 12202003
TI  - Tissue reaction to polypyrrole-coated polyester fabrics: an in vivo study in
      rats.
AB  - Electrically conductive polypyrrole is very attractive for tissue engineering
      because of its potential to modulate cellular activities through electrical
      stimulation. However, its in vivo behaviors have not been fully studied. This
      paper investigates the in vivo biocompatibility and biostability of PPy-coated
      polyester fabrics. Three PPy-coated fabrics were prepared using phosphonylation
      (PPy-Phos), plasma activation (PPy-Plas), and plasma activation plus heparin
      treatment (PPy-Plas-HE). Virgin and fluoropassivated fabrics (F-PET) were
      controls. The specimens were implanted subcutaneously in the back of rats for 3
      90 days, then harvested and processed for enzymatic, histological, and
      morphological analyses. A noninvasive MRI method was used to continuously monitor
      the inflammation. The level of acid and alkaline phosphatase showed a similar or
      a less intensive cellular reaction by the PPy-coated fabrics, when compared to
      the controls. Histology supported the enzymatic results and showed a fast
      collagen infiltration at 28 days for the PPy-Phos fabric. MRI reported an overall
      decrease of inflammation over time, with the PPy-coated fabrics showing a similar
      or mild inflammation in contrast to the non-coated fabrics. PPy clusters and
      excessive PPy laminary coating on the PPy-Plas and PPy-Plas-HE were lost with the
      implantation. This experiment suggests a similar in vivo biocompatibility of the
      PPy-coated and noncoated polyester fabrics and the importance of achieving a
      thin, uniform PPy coating.

PMID- 12202004
TI  - Tissue compatibility of two biodegradable tubular scaffolds implanted adjacent to
      skin or buccal mucosa in mice.
AB  - Radiation therapy for cancer in the head and neck region leads to a marked loss
      of salivary gland parenchyma, resulting in a severe reduction of salivary
      secretions. Currently, there is no satisfactory treatment for these patients. To
      address this problem, we are using both tissue engineering and gene transfer
      principles to develop an orally implantable, artificial fluid-secreting device.
      In the present study, we examined the tissue compatibility of two biodegradable
      substrata potentially useful in fabricating such a device. We implanted in Balb/c
      mice tubular scaffolds of poly-L-lactic acid (PLLA), poly-glycolic acid coated
      with PLLA (PGA/PLLA), or nothing (sham-operated controls) either beneath the skin
      on the back, a site widely used in earlier toxicity and biocompatibility studies,
      or adjacent to the buccal mucosa, a site quite different functionally and
      immunologically. At 1, 3, 7, 14, and 28 days postimplantation, implant sites were
      examined histologically, and systemic responses were assessed by conventional
      clinical chemistry and hematology analyses. Inflammatory responses in the
      connective tissue were similar regardless of site or type of polymer implant
      used. However, inflammatory reactions were shorter and without epithelioid and
      giant cells in sham-operated controls. Also, biodegradation proceeded more slowly
      with the PLLA tubules than with the PGA/PLLA tubules. No significant changes in
      clinical chemistry and hematology were seen due to the implantation of tubular
      scaffolds. These results indicate that the tissue responses to PLLA and PGA/PLLA
      scaffolds are generally similar in areas subjacent to skin in the back and oral
      cavity. However, these studies also identified several potentially significant
      concerns that must be addressed prior to initiating any clinical applications of
      this device.

PMID- 12202005
TI  - Fibrin microbeads for isolating and growing bone marrow-derived progenitor cells
      capable of forming bone tissue.
AB  - It has been demonstrated that bone marrow (BM)-derived pluripotent stem cells can
      be incorporated into muscle, bone, nerve, lung, stomach, intestine, and skin.
      Fibrin-based biodegradable microbeads (FMB) were developed for culturing, in
      suspension, a high density of cells, mostly of mesenchymal origin. In the current
      study, FMB were used to isolate and expand mesenchymal progenitor cells from BM
      of mice and rats. Cells from BM isolated on FMB (FMB-BM cells) were visualized by
      fluorescent confocal microscopy and quantified by a modified MTS colorimetric
      assay. Downloading the BM cells from FMB onto plastic induced their
      differentiation into islets of cells with osteogenic phenotype that secreted
      mineralized extracellular matrix. This was augmented by inducers of osteogenesis,
      such as ascorbic acid, beta-glycerophosphate, and dexamethasone, or osteoblast
      growth peptides (OGP). Implanting FMB-BM cells under the kidney capsule in mouse
      tested the osteogenic potential of these cells in vivo. Thirty days after
      implantation, bone structures with typical BM elements were seen in 8/53 kidneys
      in 6-Gy-irradiated mice and in 1/10 kidneys in nonirradiated recipients; bone
      formation was verified by soft x-ray imaging and elemental analysis that showed
      elevated Ca and Fe in the implant region. FMB-BM cells - downloaded onto plastic
      flasks, cultured for 2 weeks, mechanically harvested and then implanted - induced
      100% bone formation in both irradiated (6/6) and nonirradiated (3/3) mice.
      Histology revealed well-organized bone structures under the kidney capsule,
      including osteoblasts and typical elements of BM. Our findings demonstrate that
      FMB are capable of isolating and expanding progenitor cells from BM for
      osteogenesis and possibly for regenerating other mesenchymal tissues.

PMID- 12202006
TI  - An assessment of covalent grafting of RGD peptides to the surface of a compliant
      poly(carbonate-urea)urethane vascular conduit versus conventional biological
      coatings: its role in enhancing cellular retention.
AB  - The aim of sodding prosthetic grafts with endothelial cells (EC) is to establish
      a functioning antithrombogenic monolayer of EC. Application of basement membrane
      proteins improves EC adherence on ePTFE grafts. Their addition to a biodurable
      compliant poly(carbonate-urea)urethane graft (CPU) was studied with respect to EC
      adherence. Preclot, fibronectin, gelatin, and collagen were coated onto CPU. RGD
      peptide, heparin, and both RGD and heparin were chemically bonded to CPU. Human
      umbilical vein EC (HUVEC) labeled with 111-Indium oxine were sodded (1.8 x 10(6)
      EC/cm(2)) onto native and the modified CPU. The grafts were washed after 90 min
      and EC retention determined. The experiments were repeated six times. EC
      retention on native CPU was 1.0 +/- 0.2 x 10(5) EC/cm(2). The application of
      preclot, fibronectin, gelatin, and collagen did not improve EC retention, which
      was 0.8 +/- 0.1, 0.4 +/- 0.1, 0.3 +/- 0.08, and 0.5 +/- 0.2 x 10(5) EC/cm(2),
      respectively. Bonding RGD, heparin, and both RGD and heparin significantly
      improved EC retention to 1.9 +/- 0.6, 1.7 +/- 0.5, and 2.6 +/- 0.6 x 10(5)
      EC/cm(2), respectively (p < 0.01). Bonding of RGD, heparin, and both RGD and
      heparin accelerates and enhances EC retention onto CPU. Simple coating of
      basement membrane proteins confers no advantage over native CPU.

PMID- 12202007
TI  - Long-term stable cultures of rat hepatocytes: an in vitro model to study acute
      and chronic hepatic inflammation.
AB  - Engineered tissues provide an opportunity to investigate important physiological
      processes difficult to study in whole perfused organs and animal models. For
      example, a hepatocyte culture model consisting of rat hepatocytes cultured in a
      collagen sandwich configuration, which exhibits stable differentiated liver
      specific functions, may be useful to investigate liver pathophysiology. To
      investigate systemic inflammation-related hepatic failure, we chronically exposed
      hepatocytes to the inflammatory mediators interleukin-1beta (IL-1beta) and
      interleukin-6 (IL-6) for up to 4 weeks. IL-6 (2.5 ng/mL) transiently suppressed
      albumin (-90%) and chronically increased fibrinogen (+6-fold) production. IL-6
      inhibited urea synthesis at 2.5 ng/mL and stimulated it at 0.025 ng/mL. IL-1beta
      (10 ng/mL) inhibited albumin (-90%), urea (-40 to 50%), and IL-6-stimulated
      fibrinogen (-90%) secretion. The inhibitory effect of IL-1beta on urea secretion
      was dose-dependent. Furthermore, IL-1beta transiently stimulated nitric oxide
      (NO) synthesis; however, NO did not mediate the effect of IL-1beta on albumin and
      fibrinogen production, and played a minor role in IL-1beta-mediated urea
      synthesis suppression. In conclusion, IL-1beta and IL-6 exert, via a direct
      effect on hepatocytes, long-term inhibitory effects on hepatic functions that are
      potentially important for the survival of the host, which may contribute to
      hepatic dysfunction in prolonged inflammatory states.

PMID- 12202008
TI  - Maintenance of a functional endothelial cell monolayer on a fibroblast/polymer
      substrate under physiologically relevant shear stress conditions.
AB  - The suitability of using a fibroblast-seeded polymer scaffold as a substrate for
      forming an endothelial monolayer which is responsive to flow has been
      investigated. The results indicate that a confluent monolayer of endothelial
      cells can be formed on the top surface of the fibroblast/polymer substrate. This
      monolayer has an elongated, oriented morphology and alignment even in static
      culture, and the application of shear stress perpendicular to the endothelium's
      static alignment causes a progressive reorganization of the cytoskeletal
      component, F-actin, with a corresponding change in endothelial cell shape from
      elongated in the direction of flow, to a more "cobble-stone" morphology, to
      finally elongation in the direction of flow. The production of nitric oxide by
      this co-culture increases not only in a time and shear stress dependent fashion,
      but also as a function of the direction of flow in relation to the static
      alignment of the endothelium. The data obtained also indicate that the coculture
      had higher levels of ICAM-1 production and monocyte adhesion than seen in ECs on
      tissue culture plastic, which may be a function of the endothelial cells being in
      direct contact with the fibroblast cell line. These results demonstrate that a
      fibroblast/polymer scaffold can serve as a suitable substrate for ECs and that
      such a monolayer demonstrates the normal EC responsiveness to flow.

PMID- 12202009
TI  - Repairing large porcine full-thickness defects of articular cartilage using
      autologous chondrocyte-engineered cartilage.
AB  - Large full-thickness defects of articular cartilage remain a major challenge to
      orthopedic surgeons because of unsatisfactory results of current therapy. Many
      methods, such as chondrectomy, drilling, cartilage scraping, arthroplasty,
      transplantation of chondrocytes, periosteum, perichondrium, as well as cartilage
      and bone, have been tried to repair articular cartilage defects. However, the
      results are far from satisfactory. In this study, we applied a tissue-engineering
      approach to the repair of articular cartilage defects of knee joints in a porcine
      model. Using isolated autologous chondrocytes, polyglycolic acid (PGA), and
      Pluronic, we have successfully in vivo-engineered hyaline cartilage and repaired
      articular cartilage defects. The surface of the repaired defects appeared smooth
      at 24 weeks postrepair. Histological examination demonstrated a typical hyaline
      cartilage structure with ideal interface healing between the engineered cartilage
      and the adjacent normal cartilage and underlying cancellous bone. In addition,
      glycosaminoglycan (GAG) levels in the engineered cartilage reached 80% of that
      found in native cartilage at 24 weeks postrepair. Biomechanical analysis at 24
      weeks demonstrated that the biomechanical properties of the tissue-engineered
      cartilage were improved compared with those at an earlier stage. Thus, the
      results of this study may provide insight into the clinical repair of articular
      cartilage defects.

PMID- 12202010
TI  - Etiology of adolescent substance abuse: a developmental perspective.
AB  - Approximately 5% of adolescents in the U.S. qualify for a diagnosis of substance
      use disorder (SUD). Low affect and behavior self-regulation during child
      development interacting with family, peer and other ecological factors
      predisposes to substance use in adolescence. Maturational processes during
      adolescence, particularly involving the brain and reproductive system, exacerbate
      the low psychological self-regulation evidenced during childhood to promote
      initiation of alcohol, tobacco, and other drug (ATOD) consumption. This
      discussion examines the etiology of ATOD abuse and SUD from a developmental
      perspective. The ramifications of a developmental perspective for clinical
      practice and social policy are also considered.

PMID- 12202011
TI  - Residencies in addiction psychiatry: 1990 to 2000, a decade of progress.
AB  - This article reviews the history and status of addiction psychiatry residencies
      based on surveys conducted in 1990 and again in 1999. The 19 of 38 approved
      programs in operation since 1990 filled more positions than those that were more
      recently accredited, but they were not significantly different in time allocated
      to respective clinical assignments or in salary support. Altogether, the programs
      provide a broad array of training sites (inpatient and outpatient, alcohol and
      other-drug related) suitable for the diverse needs that graduates will encounter.
      There were, however, differences in the balance of time dedicated to research
      relative to patient care. Salaries were relatively modest and drawn from federal
      and local sources.

PMID- 12202012
TI  - Isradipine enhancement of cerebral blood flow in abstinent cocaine abusers with
      and without chronic perfusion deficits.
AB  - Nine cocaine abusers with cerebral blood flow (CBF) deficits (hypo-perfused
      areas) on HMPAO SPECT scans were compared to six without these deficits after six
      doses of isradipine (5 mg TID). When comparing the scan before isradipine to that
      after using SPM analysis, the ratio of hypo- to hyper-fusion showed a 16%
      increase in the maximum Z scores and 30% fewer areas of hypo-perfusion among
      those cocaine abusers with deficits. These deficits may represent segmental
      cerebral vasospasm that was reversed by this vasodilating agent in cocaine
      abusers with areas of hypo-perfusion (deficits) as baseline.

PMID- 12202013
TI  - Relationship between tobacco smoking and medical symptoms among cocaine-, alcohol
      , and opiate-dependent patients.
AB  - Despite widespread use of tobacco by alcohol and drug abusers, the medical
      effects of smoking remain understudied among such individuals. We investigated
      the relationship between tobacco smoking and medical symptoms among 87 cocaine-,
      98 opiate- and 81 alcohol-dependent individuals receiving outpatient treatment.
      Smoking status was assessed and medical symptoms were recorded using a
      standardized 134-item self-report instrument (MILCOM). Almost 79% of patients
      were tobacco smokers. Analysis of variance revealed a main effect of tobacco
      smoking on medical symptoms. Smokers reported significantly more symptoms on the
      total scale as well as on the respiratory, cardiovascular, gastrointestinal, and
      nose/throat subscales compared to non-smokers. Furthermore, we found a
      significant interaction between tobacco smoking and substance abuse with respect
      to medical symptoms. While opiate and alcohol patients who smoked reported more
      symptoms than those who did not, unexpectedly, cocaine users who smoked reported
      fewer symptoms than those who did not smoke. While the findings support the link
      between smoking and medical problems among substance abusers, these effects do
      not seem to be uniform across various substances of abuse. In particular, cocaine
      patients seem to be affected differently than alcohol and opiate patients.

PMID- 12202014
TI  - Alcohol use affects the outcome of treatment for cocaine abuse.
AB  - This study investigated whether alcohol use affects baseline characteristics and
      treatment outcome in 128 adults who participated in a randomized trial of
      cognitive behavioral vs. 12-step treatment for crack cocaine abuse. Assessments
      were taken at baseline and weeks 4, 8, 12, and 26 on biologically-verified
      cocaine abstinence and psychometric measures. Alcohol use was measured at intake
      and subsequent assessments using the Addiction Severity Index (ASI) and self
      reported frequency of alcohol consumption. Results indicate alcohol use at
      baseline was associated with increased baseline cocaine use and ASI drug severity
      but was not associated with ASI psychiatric severity, psychiatric diagnoses, or
      other baseline variables. Alcohol use at baseline did not predict worse treatment
      outcome for cocaine abstinence. However, alcohol use after four weeks of
      treatment did predict ability to achieve cocaine abstinence at assessment points
      during and after treatment.

PMID- 12202015
TI  - A pilot double blind placebo controlled trial of sertraline with naltrexone in
      the treatment of opiate dependence.
AB  - Naltrexone has been used for thirty years as an aid to maintenance of opiate
      abstinence with limited success. One reason is that naltrexone does not appear to
      reduce craving in opiate addiction, unlike in alcoholism. The authors conducted
      this trial of naltrexone in combination with the SSRI sertraline to assess
      treatment retention with combination pharmacotherapy. They used a double-blind
      placebo controlled trial of naltrexone 50 mg qd with placebo versus naltrexone 50
      mg plus sertraline 50 mg qd in 13 recently nondepressed abstinent opiate addicts
      followed over a 12 week period. Both groups had a similar side effect profile and
      while there was an initial trend in increased retention in the combination
      therapy group, there was no difference in retention by the end of the study.
      There was a fall in the Beck Depression Inventory scores in both groups over
      time, and there was a significant negative correlation between BDI scores and
      duration in treatment in the combination therapy group. There was a fall in
      opiate craving, as measured by an opiate craving questionnaire, over time in both
      groups. The authors conclude that combination pharmacotherapy appeared to be well
      tolerated and was initially successful in increasing treatment retention relative
      to naltrexone alone, but this effect tended to diminish over time.

PMID- 12202016
TI  - Patterns of cigarette smoking, alcohol use and other substance use among Chinese
      university students in Hong Kong.
AB  - The pattern of tobacco, alcohol, and other substance use was assessed among 1,197
      Chinese undergraduates in Hong Kong. Students reported their current and past use
      of tobacco (13%), alcohol (61%), marijuana (2%), and other illicit drugs (0.4%).
      Perceptions of risk from the use of different substances were low among those who
      use substances and among senior students. The rate of substance use was higher
      among males, residents of university hall, senior students, and among those who
      possessed a positive attitude towards substance use. There were significant
      associations between different substance uses among the respondents.

PMID- 12202017
TI  - Clinical applications of modafinil in stimulant abusers: low abuse potential.

PMID- 12202018
TI  - Fighting leprosy and other endemic diseases.
AB  - As part of its 100th-anniversary celebration, the Pan American Health
      Organization has named 12 persons as "Public Health Heroes of the Americas" in
      recognition of their noteworthy contributions to public health in the Region of
      the Americas. Over the course of this year, the Revista Panamericana de Salud
      Publica/Pan American Journal of Public Health will be carrying pieces written by
      or about these heroes. Como parte de la celebracion de su Centenario, la
      Organizacion Panamericana de la Salud (OPS) ha distinguido con el titulo de
      Heroes de la Salud Publica a 12 personalidades que se han destacado por su
      valiosa contribucion a la salud en el continente americano. A lo largo de este
      ano, la Revista Panamericana de Salud Publica/Pan American Journal of Public
      Health publicara una serie de escritos de los mismos galardonados o acerca de
      ellos.

PMID- 12202019
TI  - [Using indicators to identify regions with critical maternal health conditions].
AB  - OBJECTIVE: In early 2000 the Ministry of Health and Social Welfare of Bolivia
      brought together a group of experts who, using available information, developed a
      method that made it possible to identify critical maternal and neonatal health
      sections of the country and to create a map of the health situation and of the
      existing health-services capacity in the 112 provinces of Bolivia. The objective
      of this piece is to describe the method that those experts created and applied.
      METHODS: Two indices were created, one for the health situation and the other for
      the existing health-services capacity. The steps followed in this process were:
      1) identifying the variables included in each index, 2) weighting the variables
      in each index, 3) creating a mathematical formula for each index, 4) preparing a
      list with the data from each province for the chosen variables and with the
      percentage for each province for each index, obtained by using the respective
      formula, 5) setting three continuous-data categories for each index, and 6)
      defining the taxonomy that was possible by combining the results of the two
      indices. RESULTS: Applying this approach, a national map of the maternal health
      situation and of the existing capacity in each of the 112 Bolivian provinces was
      developed. This made it possible to choose a small number of provinces where the
      Ministry of Health and Social Welfare could work with other institutions to carry
      out joint interventions. The 9 selected provinces have a total of 26
      municipalities, which include 17 health districts and which have 29% of the
      population of the country, 33% of the maternal deaths, and an estimated 35% of
      the early neonatal deaths. CONCLUSIONS: Using available information, this method
      generated a map of the overall maternal health situation in the 112 provinces of
      Bolivia and made it possible to identify critical geographical areas for health
      interventions.

PMID- 12202020
TI  - The general public's perceptions and use of antimicrobials in Trinidad and
      Tobago.
AB  - OBJECTIVE: To determine the general public's perceptions and use of antibiotics
      in Trinidad and Tobago, a two-island republic in the Caribbean. METHODS: This
      prospective study surveyed 824 randomly selected households listed in the
      telephone directory, from November 1998 to January 1999. Through telephone
      interviews we determined knowledge about antibiotics and beliefs concerning their
      safety and efficacy. We studied the influence of age, gender, education, and
      having private health insurance on knowledge, self-medication, storing medication
      at home for emergency use ("hoarding"), and asking a private doctor to prescribe
      antibiotics ("demand prescribing"). RESULTS: For the 824 telephone calls that the
      interviewers completed, 753 of the households agreed to participate (91.4%
      response rate). Of those 753 participants, 699 of them (93%) knew the term
      "antibiotic," 29% (206/699) said it was a drug for bacterial infections, and 25%
      (170/690) had asked a doctor for an antibiotic prescription. Penicillin was
      correctly identified as an antibiotic across age, gender, and education
      categories, but 36% of respondents incorrectly said Benadryl (diphenhydramine), a
      common over-the-counter cough and cold formulation, was an antibiotic. Gender was
      not significantly associated with knowledge of antibiotic safety, with self
      medication, or with hoarding antibiotics. On the other hand, completion of
      tertiary (university) education was significantly associated with correct
      knowledge of the safety of antibiotics and whether or not they could cure all
      infections. Of the various antimicrobials, beta-lactams were the ones that survey
      respondents had used most frequently in the preceding year, and 20% of
      antibiotics users had used multiple antibiotics in that period. In comparison to
      persons with private health insurance, more individuals without private health
      insurance said that antibiotics are safe and do not have side effects, and more
      of them also incorrectly called aspirin and Benadryl antibiotics. CONCLUSIONS: In
      Trinidad and Tobago, inappropriate use of antimicrobials results from self
      medication, over-the-counter availability at the community pharmacy, prescribing
      on demand, and lack of regulatory control. In order to contain antibiotic abuse,
      both the Drug Inspectorate of the Ministry of Health and the Pharmacy Board
      should exert stricter control on the dispensing of antibiotics at private
      pharmacies. Further, education of the general public and of health care
      professionals on antibiotic misuse and appropriate use must be instituted, along
      with community-based surveillance of antimicrobial resistance trends.

PMID- 12202021
TI  - [Factors determining weight and height in children aged 3 months to 6 years
      enrolled in a public municipal day-care center in Brazil].
AB  - OBJECTIVE: To assess factors determining growth in a group of children between 3
      months and 6 years old enrolled in a public municipal (i.e., government
      supported, not private) day-care center, in comparison to a group of children
      with similar characteristics but who were not enrolled in the center. METHODS: A
      quasi-experimental study was designed to observe 444 children aged 3 to 72 months
      from a low-income neighborhood in the city of Sorocaba, in the state of Sao
      Paulo, Brazil. Two groups were studied: 164 children enrolled in a local
      municipal day-care center (intervention group) and 280 not receiving care at the
      center (nonintervention, comparison group) but instead being cared for at home.
      Both groups were seen four times over a period of 16 months. At each observation
      session, the children's weight and height were measured. Information was also
      collected on the mother's sociodemographic characteristics and the illnesses she
      had suffered as well as the child's weight and other health characteristics at
      birth, the child's illnesses in the 15 days before each observation, and any
      hospitalizations. RESULTS: The children in both groups were from low-income
      families, with 65% of the families having an average monthly income below US$
      100; 80% of the mothers had received 8 years of schooling or less. Multivariate
      linear regression analysis showed that at the first observation (just before
      enrollment in the day-care center), birth weight was the only factor that
      explained the nutritional differences between the two groups. Subsequent analyses
      showed that being in day care was the factor that best explained the differences
      between the groups, especially in terms of the adequacy of weight for age, after
      controlling for birthweight, sex, age at the beginning of the study, and
      illnesses in the 15 days before an observation session. The nutritional impact of
      the intervention was significant as early as 3 months after being enrolled in day
      care. CONCLUSIONS: The nutritional benefits of the care provided at the center
      outweighed the negative effects sometimes seen in such centers, such as the
      greater morbidity that children in day-care centers often experience in
      comparison to children receiving care at home.

PMID- 12202022
TI  - [Effect of influenza epidemics on mortality in Santa Fe, Argentina, during 1992
      1999].
AB  - OBJECTIVES: To define the effect of influenza epidemics on mortality and to
      establish the best criterion for predicting mortality so as to provide a method
      for advance warning of the severity of an influenza epidemic. METHODS: The study
      was carried out in La Capital, a department in Santa Fe province, Argentina,
      during 1992-1999. In order to fulfill the first objective, a retrospective
      analysis was performed with mortality data for pneumonia and influenza in persons
      over 65 years of age, using the auto-regressive integrated moving averages
      (ARIMA). The latter were used to determine the excess mortality attributable to
      influenza epidemics. In order to attain the second objective, a regression
      analysis was performed so as to study the correlation between weekly morbidity
      from influenza and monthly mortality from pneumonia or influenza in personas over
      65. Morbidity was expressed in terms of three summary measures which were derived
      from the number of cases of influenza that were reported during the first 35
      weeks of the year: the sum total of all cases reported weekly, their standard
      deviation, and the maximum number of cases in any given week. We included in the
      analysis the type and subtype of influenza. These four parameters (type and
      subtype of influenza, along with one of the three summary measures) were compared
      among themselves in terms of their ability to explain the mortality observed
      during the first eight months of the year. RESULTS: Epidemics occurred during the
      winters of 1993, 1995, and 1999 and in the spring of 1997. During those seasons,
      excess deaths were observed in connection with the circulation of a predominant
      strain of influenza virus, type A (H3N2). There were no epidemics in the winter
      months of 1994, 1996, and 1998, despite the circulation of this viral strain.
      During the winters in which influenza virus strains A (H1N1) and B were in
      circulation (1992 and 1997, respectively) - both are associated with low
      mortality figures - no excess deaths were detected. CONCLUSIONS: The number of
      weekly cases of influenza reported during the peak of the winter season is the
      best criterion for predicting how much excess mortality can be attributed to the
      epidemic.

PMID- 12202023
TI  - Caregiver knowledge, attitudes, and practices regarding childhood diarrhea and
      dehydration in Kingston, Jamaica.
AB  - OBJECTIVE: To study the knowledge, attitudes, and practices of caregivers in
      Kingston, Jamaica, regarding childhood diarrhea and dehydration in order to
      determine if limited caregiver knowledge about the prevention and treatment of
      diarrhea and dehydration puts children at increased risk of presenting at the
      hospital for these concerns. METHODS: The study was an observational case-control
      study conducted between February 1997 and May 1997 at Bustamante Hospital for
      Children in Kingston. Convenience sampling was used and data were collected by
      face-to-face interviews with two groups of caregivers of children under 5 years
      of age. One group (n = 117) presented with children with acute gastroenteritis,
      and the other group (n = 98) presented with acute concerns unrelated to
      gastroenteritis. While 197 of the 215 caregivers interviewed were the mother of a
      child, there were also 9 guardians, 5 fathers, and 4 grandmothers in the sample.
      RESULTS: The mean caregiver age, level of education, and socioeconomic status
      were similar for the two groups. The caregivers in the gastroenteritis group were
      more likely to present with younger children and to have less convenient access
      to running water or a refrigerator. Children of caregivers who had never heard of
      oral rehydration therapy were at increased risk of presenting with
      gastroenteritis and dehydration (odds ratio [OR], 4.6; 95% confidence interval
      [CI], 1.8-11.7), as were children of caregivers with low knowledge scores about
      the prevention and treatment of diarrhea and dehydration (OR, 3.7; 95% CI, 1.6
      8.8). Another independent risk factor was a caregiver's poor sense of self
      reliance in managing a child's diarrhea (OR, 2.3; 95% CI, 1.1-4.9). CONCLUSIONS:
      These findings highlight a need to enhance educational efforts that will empower
      caregivers to protect their children from diarrhea-associated morbidity and
      mortality.

PMID- 12202026
TI  - Gender and alcohol consumption and alcohol-related problems in Latin America and
      the Caribbean.

PMID- 12202028
TI  - Innovative care for chronic health conditions.

PMID- 12202027
TI  - [Prevention and control of influenza].
AB  - This piece summarizes a report that updates the recommendations of the Advisory
      Committee on Immunization Practices of the United States of America with regard
      to the use of the influenza vaccine and of specific antiviral agents for
      influenza. The recommended 2002-2003 trivalent vaccine virus strains are
      A/Moscow/10/99 (H3N2)-like, A/New Caledonia/20/99 (H1N1)-like, and B/Hong
      Kong/330/2001- like. The piece defines the groups who should be vaccinated and
      the persons who should not be, as well as adverse reactions to the vaccine.
      Influenza antivirals are a complement to-but not a replacement for-the vaccine in
      preventing and controlling the disease. The piece also analyzes for the antiviral
      agents the indications for their use, dosage, routes of administration,
      pharmacokinetic characteristics, interactions, and side effects.

PMID- 12202029
TI  - Brain repair by endogenous progenitors.
AB  - Stem cells within the adult brain can be stimulated by injury and growth factor
      treatment to replace damaged neurons, even neurons that are not normally
      generated in adults. Coupled with recent insights into the mechanism by which
      Nogo inhibits axonal regeneration, this discovery may inspire new treatments for
      central nervous system injuries and neurodegenerative diseases.

PMID- 12202030
TI  - Competition and compensation: coupled to death in development and cancer.
AB  - Developing systems exhibit robust and tolerant properties in the form of
      compensation and competition within cell groups. Fundamentally, these behaviors
      are governed by mechanisms that elicit proliferation and apoptosis. Recent
      insights from the Drosophila system implicate new determinants that specify
      "winners" and "losers" in this process.

PMID- 12202031
TI  - Shared strategies in gene organization among prokaryotes and eukaryotes.
AB  - Although genes in prokaryotes and eukaryotes are transcribed and translated by
      very different mechanisms, they may be organized in their respective chromosomes
      in surprisingly similar ways. Here, I examine common modes of maintaining
      nonrandom gene organization in both prokaryotes and eukaryotes, the different
      ways these organizations have likely arisen, and classes of organization that may
      be unique to one group or the other.

PMID- 12202032
TI  - Comm sorts robo to control axon guidance at the Drosophila midline.
AB  - Axon growth across the Drosophila midline requires Comm to downregulate Robo, the
      receptor for the midline repellent Slit. We show here that comm is required in
      neurons, not in midline cells as previously thought, and that it is expressed
      specifically and transiently in commissural neurons. Comm acts as a sorting
      receptor for Robo, diverting it from the synthetic to the late endocytic pathway.
      A conserved cytoplasmic LPSY motif is required for endosomal sorting of Comm in
      vitro and for Comm to downregulate Robo and promote midline crossing in vivo.
      Axon traffic at the CNS midline is thus controlled by the intracellular
      trafficking of the Robo guidance receptor, which in turn depends on the precisely
      regulated expression of the Comm sorting receptor.

PMID- 12202033
TI  - Regeneration of hippocampal pyramidal neurons after ischemic brain injury by
      recruitment of endogenous neural progenitors.
AB  - The adult brain is extremely vulnerable to various insults. The recent discovery
      of neural progenitors in adult mammals, however, raises the possibility of
      repairing damaged tissue by recruiting their latent regenerative potential. Here
      we show that activation of endogenous progenitors leads to massive regeneration
      of hippocampal pyramidal neurons after ischemic brain injury. Endogenous
      progenitors proliferate in response to ischemia and subsequently migrate into the
      hippocampus to regenerate new neurons. Intraventricular infusion of growth
      factors markedly augments these responses, thereby increasing the number of
      newborn neurons. Our studies suggest that regenerated neurons are integrated into
      the existing brain circuitry and contribute to ameliorating neurological
      deficits. These results expand the possibility of novel neuronal cell
      regeneration therapies for stroke and other neurological diseases.

PMID- 12202034
TI  - Ras and Rap control AMPA receptor trafficking during synaptic plasticity.
AB  - Recent studies show that AMPA receptor (-R) trafficking is important in synaptic
      plasticity. However, the signaling controlling this trafficking is poorly
      understood. Small GTPases have diverse neuronal functions and their perturbation
      is responsible for several mental disorders. Here, we examine the small GTPases
      Ras and Rap in the postsynaptic signaling underlying synaptic plasticity. We show
      that Ras relays the NMDA-R and CaMKII signaling that drives synaptic delivery of
      AMPA-Rs during long-term potentiation. In contrast, Rap mediates NMDA-R-dependent
      removal of synaptic AMPA-Rs that occurs during long-term depression. Ras and Rap
      exert their effects on AMPA-Rs that contain different subunit composition. Thus,
      Ras and Rap, whose activity can be controlled by postsynaptic enzymes, serve as
      independent regulators for potentiating and depressing central synapses.

PMID- 12202035
TI  - The Drosophila Hox gene deformed sculpts head morphology via direct regulation of
      the apoptosis activator reaper.
AB  - Hox proteins control morphological diversity along the anterior-posterior body
      axis of animals, but the cellular processes they directly regulate are poorly
      understood. We show that during early Drosophila development, the Hox protein
      Deformed (Dfd) maintains the boundary between the maxillary and mandibular head
      lobes by activating localized apoptosis. Dfd accomplishes this by directly
      activating the cell death promoting gene reaper (rpr). One other Hox gene,
      Abdominal-B (Abd-B), also regulates segment boundaries through the regional
      activation of apoptosis. Thus, one mechanism used by Drosophila Hox genes to
      modulate segmental morphology is to regulate programmed cell death, which
      literally sculpts segments into distinct shapes. This and other emerging evidence
      suggests that Hox proteins may often regulate the maintenance of segment
      boundaries.

PMID- 12202036
TI  - salvador Promotes both cell cycle exit and apoptosis in Drosophila and is mutated
      in human cancer cell lines.
AB  - The number of cells in an organism is determined by regulating both cell
      proliferation and cell death. Relatively few mechanisms have been identified that
      can modulate both of these processes. In a screen for Drosophila mutations that
      result in tissue overgrowth, we identified salvador (sav), a gene that promotes
      both cell cycle exit and cell death. Elevated Cyclin E and DIAP1 levels are found
      in mutant cells, resulting in delayed cell cycle exit and impaired apoptosis.
      Salvador contains two WW domains and binds to the Warts (or LATS) protein kinase.
      The human ortholog of salvador (hWW45) is mutated in three cancer cell lines.
      Thus, salvador restricts cell numbers in vivo by functioning as a dual regulator
      of cell proliferation and apoptosis.

PMID- 12202037
TI  - Class II histone deacetylases act as signal-responsive repressors of cardiac
      hypertrophy.
AB  - The heart responds to stress signals by hypertrophic growth, which is accompanied
      by activation of the MEF2 transcription factor and reprogramming of cardiac gene
      expression. We show here that class II histone deacetylases (HDACs), which
      repress MEF2 activity, are substrates for a stress-responsive kinase specific for
      conserved serines that regulate MEF2-HDAC interactions. Signal-resistant HDAC
      mutants lacking these phosphorylation sites are refractory to hypertrophic
      signaling and inhibit cardiomyocyte hypertrophy. Conversely, mutant mice lacking
      the class II HDAC, HDAC9, are sensitized to hypertrophic signals and exhibit
      stress-dependent cardiomegaly. Thus, class II HDACs act as signal-responsive
      suppressors of the transcriptional program governing cardiac hypertrophy and
      heart failure.

PMID- 12202038
TI  - Crucial step in cholesterol homeostasis: sterols promote binding of SCAP to INSIG
      1, a membrane protein that facilitates retention of SREBPs in ER.
AB  - Using coimmunoprecipitation and tandem mass spectrometry, we identify INSIG-1 as
      an ER protein that binds the sterol-sensing domain of SREBP cleavage-activating
      protein (SCAP) and facilitates retention of the SCAP/SREBP complex in the ER. In
      sterol-depleted cells, SCAP escorts SREBPs from ER to Golgi for proteolytic
      processing, thereby allowing SREBPs to stimulate cholesterol synthesis. Sterols
      induce binding of SCAP to INSIG-1, as determined by blue native-PAGE, and this is
      correlated with the inhibition of SCAP exit from the ER. Overexpression of INSIG
      1 increases the sensitivity of cells to sterol-mediated inhibition of SREBP
      processing. Mutant SCAP(Y298C) fails to bind INSIG-1 and is resistant to sterol
      mediated inhibition of ER exit. By facilitating sterol-dependent ER retention of
      SCAP, INSIG-1 plays a central role in cholesterol homeostasis.

PMID- 12202039
TI  - Modular recognition of RNA by a human pumilio-homology domain.
AB  - Puf proteins are developmental regulators that control mRNA stability and
      translation by binding sequences in the 3' untranslated regions of their target
      mRNAs. We have determined the structure of the RNA binding domain of the human
      Puf protein, Pumilio1, bound to a high-affinity RNA ligand. The RNA binds the
      concave surface of the molecule, where each of the protein's eight repeats makes
      contacts with a different RNA base via three amino acid side chains at conserved
      positions. We have mutated these three side chains in one repeat, thereby
      altering the sequence specificity of Pumilio1. Thus, the high affinity and
      specificity of the PUM-HD for RNA is achieved using multiple copies of a simple
      repeated motif.

PMID- 12202040
TI  - Prediction of plant microRNA targets.
AB  - We predict regulatory targets for 14 Arabidopsis microRNAs (miRNAs) by
      identifying mRNAs with near complementarity. Complementary sites within predicted
      targets are conserved in rice. Of the 49 predicted targets, 34 are members of
      transcription factor gene families involved in developmental patterning or cell
      differentiation. The near-perfect complementarity between plant miRNAs and their
      targets suggests that many plant miRNAs act similarly to small interfering RNAs
      and direct mRNA cleavage. The targeting of developmental transcription factors
      suggests that many plant miRNAs function during cellular differentiation to clear
      key regulatory transcripts from daughter cell lineages.

PMID- 12202041
TI  - HIV-1 integration in the human genome favors active genes and local hotspots.
AB  - A defining feature of HIV replication is integration of the proviral cDNA into
      human DNA. The selection of chromosomal targets for integration is crucial for
      efficient viral replication, but the mechanism is poorly understood. Here we
      describe mapping of 524 sites of HIV cDNA integration on the human genome
      sequence. Genes were found to be strongly favored as integration acceptor sites.
      Global analysis of cellular transcription indicated that active genes were
      preferential integration targets, particularly genes that were activated in cells
      after infection by HIV-1. Regional hotspots for integration were also found,
      including a 2.4 kb region containing 1% of sites. These data document
      unexpectedly strong biases in integration site selection and suggest how
      selective targeting promotes aggressive HIV replication.

PMID- 12202042
TI  - SUMO-1 modification of Mdm2 prevents its self-ubiquitination and increases Mdm2
      ability to ubiquitinate p53.

PMID- 12202044
TI  - Dermal absorption in rhesus monkeys of polychlorinated biphenyls from soil
      contaminated with Aroclor 1260.
AB  - Human health risk assessments involving contaminated soil include dermal
      absorption as a potential pathway contributing to the total exposure burden. For
      PCB-contaminated soil, the U.S. Environmental Protection Agency uses a dermal
      absorption factor of 14%, based on a 1993 study of dermal absorption in rhesus
      monkeys. The current study examined several parameters that can influence the
      dermal absorption of lipophilic hydrocarbons, including soil organic content,
      particle size, skin residence time, and contaminant "aging" in the soil. Four
      groups of four female rhesus monkeys each were exposed to radiolabeled Aroclor
      1260 either intravenously (100% absorption) or dermally with PCB-spiked soil.
      Groups exposed for 12 or 24 h to PCBs aged in soil exhibited percutaneous
      absorption values of 3.43 +/- 0.35 and 4.26 +/- 0.52%, respectively, while a
      group exposed for 24 h to soil freshly spiked with PCBs exhibited a dermal
      absorption value of 4.07 +/- 0.46%. Evidence strongly suggests that the factor
      most responsible for modulating the percutaneous absorption of highly lipophilic
      compounds from soil is its organic content. The base soil used in the current
      study with Aroclor 1260 had an organic content of 5-6% (< or =2 mm particle
      fraction), a value typical for U.S. soil. The organic content of the soil applied
      to the skin was 8.7% (<150 microm particle fraction), a value that contrasts
      sharply with the soil containing 0.9% organics used in the 1993 study with
      Aroclors 1242 and 1254 that produced a dermal absorption value of 14% for PCBs.

PMID- 12202045
TI  - Toxicological studies on Laccase from Myceliophthora thermophila expressed in
      Aspergillus oryzae.
AB  - The bioindustrially produced enzyme laccase can be used in different technical
      and food applications to facilitate processes. It can be added to different oral
      care products such as mouthwash, toothpaste, mints, and gums to prevent
      halitosis. Laccase, produced by submerged fermentation of Aspergillus oryzae,
      containing a gene originating from Myceliophthora thermophila, was subject to a
      series of toxicological tests to document its safety in use. It was not found to
      be mutagenic in the Salmonella typhimurium reverse mutation assay, nor did it
      cause chromosomal aberrations in cultured human lymphocytes. No evidence of
      inhalation toxicity or skin and eye irritation was found. There was no evidence
      of possible skin sensitization in a human skin sensitization test when Laccase
      was tested at 10% (w/v): thus Laccase would appear to have a low skin
      sensitization potential. Oral administration to rats of up to 10.0 mL/kg body
      wt/day (equivalent to a total organic solids dosage of 1.72 g/kg body wt/day) for
      13 weeks did not cause any adverse effect.

PMID- 12202046
TI  - Styrene respiratory tract toxicity and mouse lung tumors are mediated by CYP2F
      generated metabolites.
AB  - Mice are particularly sensitive to respiratory tract toxicity following styrene
      exposure. Inhalation of styrene by mice results in cytotoxicity in terminal
      bronchioles, followed by increased incidence of bronchioloalveolar tumors, as
      well as degeneration and atrophy of nasal olfactory epithelium. In rats, no
      effects on terminal bronchioles are seen, but effects in the nasal olfactory
      epithelium do occur, although to a lesser degree and from higher exposure
      concentrations. In addition, cytotoxicity and tumor formation are not related to
      blood levels of styrene or styrene oxide (SO) as measured in chronic studies.
      Whole-body metabolism studies have indicated major differences in styrene
      metabolism between rats and mice. The major differences are 4- to 10-fold more
      ring-oxidation and phenylacetaldehyde pathways in mice compared to rats. The data
      indicate that local metabolism of styrene is responsible for cytotoxicity in the
      respiratory tract. Cytotoxicity is seen in tissues that are high in CYP2F P450
      isoforms. These tissues have been demonstrated to produce a high ratio of R-SO
      compared to S-SO (at least 2.4 : 1). In other rat tissues the ratio is less than
      1, while in mouse liver the ratio is about 1.1. Inhibition of CYP2F with 5-phenyl
      1-pentyne prevents the styrene-induced cytotoxicity in mouse terminal bronchioles
      and nasal olfactory epithelium. R-SO has been shown to be more toxic to mouse
      terminal bronchioles than S-SO. In addition, 4-vinylphenol (ring oxidation of
      styrene) has been shown to be highly toxic to mouse terminal bronchioles and is
      also metabolized by CYP2F. In human nasal and lung tissues, styrene metabolism to
      SO is below the limit of detection in nearly all samples, and the most active
      sample of lung was approximately 100-fold less active than mouse lung tissue. We
      conclude that styrene respiratory tract toxicity in mice and rats, including
      mouse lung tumors, are mediated by CYP2F-generated metabolites. The PBPK model
      predicts that humans do not generate sufficient levels of these metabolites in
      the terminal bronchioles to reach a toxic level. Therefore, the postulated mode
      of action for these effects indicates that respiratory tract effects in rodents
      are not relevant for human risk assessment.

PMID- 12202047
TI  - Assessment of mortality in patients enrolled in a risedronate clinical trial
      program: a retrospective cohort study.
AB  - Risedronate, a pyridinyl bisphosphonate, has been shown in large clinical trials
      to be effective in the prevention and treatment of osteoporosis. Analysis of
      safety data from these trials has shown that risedronate (2.5- and 5-mg doses)
      has an overall safety profile comparable to placebo during the course of the
      clinical trials. The clinical trials were powered appropriately to analyze the
      efficacy endpoints; however, patients were not systematically followed after
      completion of the clinical trials and therefore vital status for most of the
      patient cohort after the cessation of the clinical trials was unknown. In order
      to investigate further the safety profile of risedronate observed in the clinical
      trials database, we conducted a retrospective cohort mortality study among 7981
      patients comprising the intent-to-treat population in three North American
      risedronate osteoporosis trials. No difference in all cause mortality was
      observed in patients receiving risedronate treatment compared with patients
      receiving placebo. There were also no differences between these groups in
      mortality due to all cancers, lung cancer, and gastrointestinal tract cancer. A
      trend toward lower cardiovascular mortality was observed in the risedronate
      groups compared with placebo; this difference was largely due to a significant
      reduction in stroke mortality in the active treatment groups. Follow-up mortality
      data in this retrospective cohort study demonstrate that treatment with
      risedronate has no effect on overall mortality rates.

PMID- 12202048
TI  - What's wrong with the National Ambient Air Quality Standard (NAAQS) for fine
      particulate matter (PM(2.5))?
AB  - Associations between airborne concentrations of fine particulate matter (PM(2.5))
      and mortality rates have been investigated primarily by ecologic or semiecologic
      epidemiology studies. Many investigators and regulatory agencies have inferred
      that the weak, positive association often observed is causal, that it applies to
      all forms of airborne PM(2.5), and that current ambient levels of PM(2.5) require
      reduction. Before implementing stringent regulations of ambient PM(2.5), analysts
      should pause to consider whether the accumulated evidence is sufficient, and
      sufficiently detailed, to support the PM(2.5) National Ambient Air Quality
      Standard. We take two tacks. First, we analyze the toxicologic evidence, finding
      it inconsistent with the notion that current ambient concentrations of all forms
      of fine particulate matter should affect pulmonary, cardiac, or all-cause
      mortality rates. More generally, we note that the thousands of forms of PM(2.5)
      are remarkably diverse, yet the PM(2.5) NAAQS presumes them to be identical
      toxicologically, and presumes that reducing ambient concentrations of any form of
      PM(2.5) will improve public health. Second, we examine the epidemiologic evidence
      in light of two related examples of semiecologic associations, examples that both
      inform the PM-mortality association and have been called into question by
      individual-level data. Taken together, the toxicologic evidence and lessons
      learned from analogous epidemiologic associations should encourage further
      investigation of the association between particulate matter and mortality rates
      before additional regulation is implemented, and certainly before the association
      is characterized as causal and applicable to all PM(2.5).

PMID- 12202049
TI  - Evaluation of the adequacy of published studies of low-dose effects of bisphenol
      A on the rodent prostate for use in human risk assessment.
AB  - Studies conducted in our laboratories and by others found no consistent
      correlation between prostate size, prostate pathology, or the development of
      prostate cancer under a variety of experimental conditions. Furthermore, an
      evaluation of eight published studies that were conducted in mice and rats
      following in utero exposure by oral treatment of dams with low levels of
      bisphenol A (BPA) and that focused on the prostate identified several
      discrepancies that affect their adequacy for use in human risk assessment. For
      example, there was inadequate reporting of the purity of BPA and the animal
      supplier used, and housing of offspring was not the same among the studies. In
      addition, there were differences between studies with mice and rats in exposure
      regimen, route of exposure, and numbers of dams or pups used per BPA dose group.
      Poor inter- and intraspecies correlation (i.e., mouse to rat or between mouse or
      rat strains) further complicates the ability to use results from these studies to
      predict potential prostate effects in humans. Thus, we conclude that a finding of
      increased prostate weight in rodent studies with perinatal exposure in the
      absence of associated pathologic and/or functional changes is meaningless and not
      indicative of a potential adverse effect in humans.

PMID- 12202050
TI  - Evaluation of risk assessment guideline levels for the chemical warfare agents
      mustard, GB, and VX.
AB  - The U.S. Army has estimated acute lethality guideline levels for inhalation of
      the chemical warfare agents mustard, GB, and VX. These levels are expressed as
      dosages measured in milligram-minutes per cubic meter (mg-min/m(3)). The National
      Advisory Council has also proposed acute emergency guideline levels (AEGLs) for
      the agents. The AEGLs are threshold exposure limits for the general public for
      mild effects, serious adverse effects, and lethality. They are expressed as air
      concentrations (in units of mg/m(3)) and are applicable to emergency exposure
      periods ranging from 10 min to 8 h. The report discusses strengths and
      deficiencies in the levels, important parameters (i.e., exposure time, breathing
      rate) that need to be explicitly addressed in deriving the guideline levels, and
      possible impacts that could result from using AEGLs instead of guideline dosages
      in future assessments.

PMID- 12202051
TI  - Indices of fiber biopersistence and carcinogen classification for synthetic
      vitreous fibers (SVFs).
AB  - It is generally accepted that the biopersistence of a synthetic vitreous fiber
      (SVF) is an important determinant of its biological activity. Experimental
      protocols have been developed to measure the biopersistence of an SVF from short
      term inhalation experiments with rats. Clearance kinetics of long (>20 microm)
      fibers (those believed to have greatest biological activity) have been
      approximated by one- or two-pool models. Several measures or indices of
      biopersistence have been proposed in the literature of which three, the weighted
      half-time (WT(1/2)), the time required to clear 90% of long fibers (T(0.9)), and
      the so-called slow-phase half-time (T(2)), have been investigated in some detail.
      This paper considers both one- and two-pool models for long fiber clearance,
      characterizes the properties of these candidate indices of fiber biopersistence,
      identifies measures with potentially superior statistical properties, suggests
      possible cutoff values based on the relation between biopersistence and the
      outcome of chronic bioassays, and offers comments on the selection of efficient
      experimental designs. This analysis concludes that WT(1/2) and T(0.9) are highly
      correlated, are efficient predictors of the outcome of chronic bioassays, and
      have reasonable statistical properties. T(2), although perhaps attractive in
      principle, suffers from some statistical shortcomings when estimated using
      present experimental protocols. The WT(1/2) is shown to be directly proportional
      to the cumulative exposure (fiber days) after the cessation of exposure and also
      the mean residence time of these fibers in the lung.

PMID- 12202052
TI  - Screening for in vivo (anti)estrogenic and (anti)androgenic activities of
      technical and formulated deltamethrin.
AB  - Concern over the possibility of hormonal systems being disrupted by chemicals in
      the environment has led to the development of assays to detect such chemicals.
      Technical and formulated deltamethrin, a widely used synthetic pyrethroid
      pesticide, was screened for (anti)estrogenic and (anti)androgenic activities by
      means of two major in vivo short-term screening tests: the uterotrophic and
      Hershberger assays. The results reported here indicate the absence of in vivo
      (anti)estrogenic and (anti)androgenic activities for both technical and
      formulated deltamethrin at the dose levels tested (2.0 and 4.0 mg/kg/day).
      However, further tests, including in vitro screening assays, are required to
      characterize fully the lack of endocrine action of these chemicals.

PMID- 12202053
TI  - Antagonism--no synergism--in pairwise tests of carcinogens in rats.
AB  - In the mid-1970s, the National Cancer Institute issued a contract for the testing
      of a dozen chemicals, most of them known to be carcinogenic in animals, in
      pairwise combinations. Those tests, which involved 918 pairwise tests and over
      14,500 laboratory rats, produced no good evidence for any synergistic
      interactions in which exposure to two chemicals resulted in a number of tumors
      greater than the number produced by exposure to either chemical alone. A number
      of tests resulted in antagonism, in which the number of tumors in animals exposed
      to a pair of carcinogens was less than the number seen after exposure to either
      carcinogen by itself. More generally, the results indicate that synergism is an
      unlikely consequence when animals are exposed to pairs of chemicals, even when
      both chemicals are carcinogens.

PMID- 12202054
TI  - Concept evaluation: an assay for receptor-mediated and biochemical antiestrogens
      using pubertal rats.
AB  - At present, assessment of chemicals for receptor-mediated antiestrogenic activity
      involves inhibition of uterine growth stimulated by coadministration of a
      reference estrogen in either ovariectomized or immature rodents. In the present
      paper, we describe an alternative assay for both receptor-mediated and
      biochemical antiestrogens. The assay involves treatment of immature rats from
      postnatal (pnd) 25 or 26 for either 7 or 14 days and monitors two benchmarks of
      puberty, the mean day of vaginal opening and the weight of the uterus, that
      require estrogen activity. The receptor-mediated antiestrogens ZM 189,154 and
      Faslodex (ICI 182,780), the aromatase inhibitor Arimidex (Anastrozole), and the
      GnRH inhibitor Antarelix were each effective in preventing uterine growth and in
      delaying vaginal opening for the course of the experiments. The 5alpha-reductase
      inhibitor Finasteride was inactive in the assay indicating assay specificity for
      antiestrogens. Delays in uterine growth were clearly evident in the 7-day
      experiments, but assessment of vaginal opening required the 14-day protocol. No
      significant changes in body weight were observed in any of the experiments. It is
      concluded that the assay holds promise as a simple method of detecting
      antiestrogens and that it is worthy of further study.

PMID- 12202056
TI  - Hormesis and high-risk groups.
AB  - The concept of hormesis (i.e., biological phenomena characterized by dose
      response relationships displaying low-dose stimulation and high-dose inhibition)
      has important implications for current risk assessment practices because of its
      generalizability with respect to experimental model, agent, and endpoint
      measured. This paper addresses the question of whether hormesis is present in
      high-risk subpopulations and highly susceptible species. Evaluation of published
      data revealed that hormetic dose-response relationships occur with similar
      quantitative characteristics among species and individuals that display widely
      differing susceptibility to various toxicants. This observation suggests that the
      cause of the differential susceptibility in the more susceptible organisms is not
      due to the absence of the hormetic response but to some other factor(s). However,
      despite the recognition that hormetic responses are common and similar in
      susceptible and resistant organisms there are sufficient examples indicating that
      some strains/individuals may lack the capacity to produce the low-dose
      stimulatory response. Thus, the capacity to display hormetic effects is one of a
      variety of factors affecting differential susceptibility to xenobiotics and needs
      to be addressed within the hazard assessment process.

PMID- 12202055
TI  - Safety evaluation of monophosphoryl lipid A (MPL): an immunostimulatory adjuvant.
AB  - Animal models have shown the potential use of monophosphoryl lipid A (MPL), a
      detoxified bacterial lipopolysaccharide, as a vaccine adjuvant. Immunostimulatory
      activity with diverse effects on the cellular elements of the immune system has
      been demonstrated and a range of vaccines incorporating MPL, including allergy
      vaccines, are currently under clinical evaluation. A series of preclinical safety
      investigations was performed to support clinical use of MPL as used in allergy
      vaccines and comprised cardiovascular/respiratory assessment in dog (up to 100
      microg/kg/day); repeat-dose toxicity in rat, rabbit, and dog (up to 2500 and 1200
      microg/kg/day in the rat and dog, respectively); reproduction toxicity in rat and
      rabbit (up to 100 microg/kg/day); and genotoxicity studies. Overall, repeat-dose
      toxicity studies in the rat and dog showed expected immunostimulatory effects
      and/or signs of toxicity associated with overstimulation of the immune system
      (notably increased spleen weight and white blood cell values). Studies in the
      rabbit with weekly doses of MPL produced no effects. MPL was shown to have no
      adverse effects on cardiovascular/respiratory function, reproduction, and
      genotoxicity.

PMID- 12202057
TI  - Differential sensitivity of children and adults to chemical toxicity. I.
      Biological basis.
AB  - Children, particularly neonates, can be biologically more sensitive to the same
      toxicant exposure on a body weight basis than adults. Current understanding of
      the rates of maturation of metabolic capability and evidence from case examples
      on pharmaceuticals, drugs of abuse, environmental contaminants, and dietary and
      endogenous agents indicate that human infants up to approximately 6 months of age
      are typically--but not always--more sensitive to chemical toxicity than adults.
      For most chemicals, the immaturity of infant biotransformation, elimination, and
      other physiologic systems usually produces higher blood levels for longer
      periods. There is metabolic capacity for most tested substances in the newborn,
      although it is quite low and immature for some chemicals. For some chemicals,
      unique metabolic pathways not available in the adult human can also be utilized
      by the newborn. The newborn's metabolic capacity rapidly matures and, by about 6
      months of age, children are usually not more sensitive to chemical toxicity than
      adults. By then, most metabolic systems are reasonably mature, becoming almost
      completely capable by 1 year of age. In many cases children are less sensitive
      than adults. Whether children are at greater risk from chemical exposures is
      another question. Risk depends on both inherent sensitivity and exposure
      conditions. If chemical exposure levels remain below those capable of
      overwhelming a child's metabolic detoxification systems and producing toxicity,
      children will be at no greater risk than are adults. Children of all ages are
      still developing so even if they are exposed to chemicals at levels below those
      of adults, they may be at greater risk than adults. However, as long as those
      exposure levels are still below those required to produce toxicity, children will
      not be at greater risk.

PMID- 12202058
TI  - Differential sensitivity of children and adults to chemical toxicity. II. Risk
      and regulation.
AB  - Animals can be useful predictors of chemical hazards to humans. Growth and
      development are compressed into a shorter period in animals, which makes
      interpretation of animal testing inherently more difficult. However, similar
      events occur in both humans and laboratory animals and testing that covers the
      full period of animal development can reasonably be considered an appropriate
      surrogate for human development. Some have proposed an additional 10-fold factor
      for the extra protection of children when estimating safe exposures. Use of such
      an additional factor, as required by the Food Quality Protection Act (FQPA), is
      meant to address the same issues covered by the EPA's database uncertainty
      factor, UF(D), and additional issues related to exposure uncertainty. Thus, when
      UF(D) has already been deployed, the EPA modifies its use of the FQPA factor.
      Based on our analysis, we agree with the EPA. Drawing conclusions about the
      adequacy of UF(H), the uncertainty factor used to account for intrahuman
      variability, in terms of its ability to protect children on the basis of the
      modest data available is challenging. However, virtually all studies available
      suggest that a high percentage of the population, including children, is
      protected by using a 10-fold uncertainty factor for human variability or by using
      a 3.16-fold factor each for toxicokinetic and toxicodynamic variability. Based on
      specific comparisons for newborns, infants, children, adults, and those with
      severe disease, the population protected is between 60 and 100%, with the studies
      in larger populations that include sensitive individuals suggesting that the
      value is closer to 100%.

PMID- 12202060
TI  - Procedures for health risk assessment in Europe.

PMID- 12202059
TI  - The effects of atrazine on the sexual maturation of female rats.
AB  - The mammalian hazard assessment of the herbicide atrazine (ATR) has focused on
      the induction of mammary tumors and accelerated reproductive aging of adult rats,
      and the relationship of these effects to the inhibition of leutinizing hormone
      (LH) release from the pituitary, an effect itself caused by inhibition of GnRH
      signaling by the adult rat hypothalamus. In earlier studies, Laws et al.
      (Toxicol. Sci., 58, 366-376, 2000) demonstrated a delay in female rat sexual
      maturation induced by ATR, effects that could equally have been caused by
      inhibition of hypothalamic GnRH release. The present studies were designed to
      compare the doses that interfere with GnRH signaling seen in previous studies in
      adult Sprague-Dawley (SD) rats (LH surge suppression) with doses that impair GnRH
      signaling in peripubertal rats, as indicated by delayed sexual maturation. The
      studies evaluated the effects of ATR treatment on the timing of uterine growth
      and vaginal opening (VO) in peripubertal female Wistar (Alderley Park, AP) and SD
      rats. Doses of 10, 30, and 100 mg/kg ATR were administered daily from postnatal
      day (pnd) 21 to up to pnd 46. Determinations of uterine weight were made at pnd
      30, 33, 43 (AP), and 46 (SD) and the timing of VO was also assessed in the last
      two of these experiments. The centrally acting GnRH antagonist Antarelix (ANT)
      was used as a positive control agent as it has previously been shown to prevent
      uterine growth and to delay VO in peripubertal AP rats. Uterine growth and VO
      were completely prevented in AP rats exposed to ANT. Uterine growth was delayed
      at pnd 30 and 33 in AP rats exposed to 100 mg/kg ATR, but this growth inhibition
      had been overcome by pnd 43. VO was significantly delayed in AP rats for the 100
      mg/kg ATR dose. By pnd 46, VO was significantly delayed in SD rats exposed to
      both 30 and 100 mg/kg ATR, but uterine weights were unaffected by that time (as
      for AP rats). It is concluded that the no-effect level for the effects of ATR on
      sexually immature rats (10 mg/kg in SD; 30 mg/kg AP) is approximately the same as
      reported previously by Laws et al. in peripubertal Wistar rats (25 mg/kg).
      However, the no-effect level in peripubertal female SD rats is nearly an order of
      magnitude greater than the no-observed effect level observed in female SD rats
      fed ATR for 6 months (1.8 mg/kg) where LH suppression was used as an indicator of
      effect on the pituitary/hypothalamic axis (USEPA, Atrazine-DACT Fourth Report of
      the Hazard Identification and Review Committee, April 5, 2002). These results
      support the conclusion that the pituitary/hypothalamic axis in peripubertal
      female SD rats is less sensitive than that in adult female SD rats.

PMID- 12202061
TI  - Are people being screened for colorectal cancer as recommended? Results from the
      National Health Interview Survey.
AB  - BACKGROUND: The evidence is now compelling that colorectal cancer incidence and
      mortality can be reduced by screening, and medical organizations recommend
      regular screening among persons of average risk aged 50 years or older. We sought
      to determine whether appropriate screening has become more widespread now that
      consensus over its value has been achieved. METHODS: We analyzed data from the
      1992 and 1998 National Health Interview Survey, an in-person survey of a
      nationally representative sample of the U.S. population. Persons aged > or =50
      years (4428 in 1992, 12,629 in 1998) were questioned about their use of
      colorectal cancer screening. RESULTS: Self-reported use of fecal occult blood
      testing and proctoscopy increased slightly from 1992 to 1998. In 1998, however,
      only an estimated 22.9% of Americans aged > or =50 years had been screened with
      either the home-administered fecal occult blood testing in the past year or
      proctoscopy within 5 years. Nearly half of fecal occult blood testings were
      performed with a sample taken during an in-office physical examination rather
      than with the recommended home kit. CONCLUSION: Most eligible persons are still
      not meeting the screening recommendations for colorectal cancer. Education is
      needed for both the public and health care providers to increase their compliance
      with current guidelines.

PMID- 12202062
TI  - Colon cancer screening in the ambulatory setting.
AB  - BACKGROUND: Despite evidence of decreased mortality, recommendations for colon
      cancer screening have not been widely implemented by physicians. The objective of
      this study was to determine patient and clinician factors associated with
      screening for colon cancer. METHODS: A retrospective review of computerized
      medical records from primary care practices in an academic medical center was
      performed. Patients comprised men and women aged 50-74 with at least one visit
      between July 1, 1995 and June 30, 1997. Measurements included Fecal occult blood
      testing in the past 1 or 2 years, sigmoidoscopy in the previous 5 or 10 years, or
      colonoscopy in the past 10 years. RESULTS: A total of 6,039 patients were
      included in the analysis. Fecal occult blood testing had been performed in 44% of
      patients and sigmoidoscopy in 26%. Fifty-three percent of patients had undergone
      some type of colon cancer screening. In multivariate analysis, patient factors
      predictive of fecal occult blood testing included age (odds ratio (OR) per 5
      years 1.05; 95% confidence interval 1.04, 1.06), Asian ethnicity (OR 1.23; 1.08,
      1.41), number of visits during the study period (OR 1.05; 1.04, 1.06), recency of
      the last visit (OR 1.03; 1.02, 1.04), and having private insurance (OR 1.65;
      1.04, 2.62). Predictors of sigmoidoscopy were similar except that patients with a
      family history of colon cancer and those with managed care insurance were also
      more likely to undergo sigmoidoscopy. Patients of nurse practitioners were less
      likely to receive fecal occult blood testing than were patients of physicians (OR
      0.78; 0.65, 0.93). Patients of residents were less likely to undergo
      sigmoidoscopy than were patients of faculty (OR 0.79; 0.66, 0.94). CONCLUSIONS:
      Among patients seen in primary care practices, rates of colon cancer screening
      remain low, especially in patients who are younger, who have been seen less
      frequently, who are uninsured, or who do not have managed care insurance. Future
      research should explore these differences and should focus on increasing
      screening in all patient groups, especially in those who are underscreened.

PMID- 12202063
TI  - Clustering of lifestyle risk factors in a general adult population.
AB  - BACKGROUND: The objective of the study was to evaluate the degree of clustering
      of common lifestyle risk factors in a general adult population and to define
      subgroups with elevated clustering. METHODS: Data on lifestyle risk factors
      (smoking, low vegetable and fruit consumption, excessive alcohol intake, and low
      physical activity), sociodemographics, and health perception were collected by
      questionnaire from 16,789 men and women aged 20 to 59. RESULTS: About 20% of the
      subjects had at least three lifestyle risk factors. Prevalence of risk factors
      was higher among unemployed, low-educated subjects and those who had experienced
      health deterioration. All lifestyle risk factors showed significant clustering,
      except for low physical activity and excessive alcohol consumption. The strongest
      association was observed for alcohol and smoking (prevalence odds ratio (POR):
      2.38; 95% confidence interval: 2.18-2.61). Clustering of smoking and alcohol
      consumption was strongest among the young subjects (POR: 3.78) and, although
      moderately, clustering of lifestyle risk factors was elevated in subjects who had
      experienced a deterioration in health. CONCLUSIONS: These findings suggest that
      common lifestyle risk factors cluster among adult subjects. The tendency for risk
      factors to aggregate has important implications for health promotion. Information
      on high-risk groups will help in planning future preventive strategies.

PMID- 12202064
TI  - Health status and hospital utilization of recent immigrants to New York City.
AB  - BACKGROUND: This paper examines hospital utilization, estimated hospital costs,
      and mortality rates for U.S.-born, foreign-born, and Puerto Rican-born persons
      residing in New York City. METHODS: We conducted a multivariate regression
      analysis using New York City neighborhoods as the unit of analysis. We utilized
      data from the Statewide Planning and Research Cooperative System data set and
      from the 1997 Housing and Vacancy Survey. We also examined mortality rates using
      1990 death certificate data and decennial census data. RESULTS: The foreign-born
      are much less likely to be hospitalized for most major categories of illness and
      have lower mortality rates than either U.S.-born or Puerto Rican-born New
      Yorkers. The life expectancy at 1 year of age of the foreign-born is 4 years
      longer than for U.S.-born persons and 6 years longer than Puerto Rican-born
      persons. We estimate that the overall cost of providing hospital-based care to
      the foreign-born was $611 million US dollars less than the cost of providing
      hospital-based care to an equivalent number of U.S.-born persons in 1996.
      CONCLUSION: The foreign-born in New York City appear to be healthier and consume
      fewer hospital resources than U.S.-born populations. It is possible that the cost
      of hospital utilization would be lower still if the foreign-born population had
      better access to ambulatory and preventive services.

PMID- 12202066
TI  - Effectiveness of the "Smoke-Free Class Competition" in delaying the onset of
      smoking in adolescence.
AB  - BACKGROUND: This paper examines the effectiveness of the "Smoke-Free Class
      Competition" in delaying the onset of smoking in adolescence. Each participating
      class must decide if they want to be a "smoke-free class" for the 6-month period
      from fall to spring. Classes monitor their (non-)smoking behavior and report it
      to the teacher regularly. Classes in which pupils refrain from smoking for this
      period of time participate in a prize draw, in which they can win a number of
      attractive prizes. METHODS: To evaluate the effectiveness of the competition, a
      sample of 131 participating and nonparticipating classes (number of pupils 2,142;
      mean age 12.9 years, SD = 0.98) was compared with regard to their smoking
      behavior. Smoking status was determined by self-assessment on three occasions:
      (a) prior to the beginning of the competition, (b) 1 month after the competition,
      and (c) 1 year after the start of the competition. RESULTS: From pretest to
      posttest smoking increased by 7.5% in the comparison group, while it decreased by
      0.2% in the intervention group (OR = 2.19; P < 0.001). In the follow-up
      measurement, a clear increase in smoking prevalence occurs in all groups;
      however, the pupils in the intervention condition still have a significant lower
      increase of smoking (OR = 1.45; P < 0.01). Moreover, with regard to the
      nonsmokers at baseline, pupils in the comparison group showed significantly
      higher prevalences in smoking than the intervention group in the postmeasurement,
      7.8 versus 13.9% (OR = 1.98; P < 0.001), as well as in the in the follow-up
      measurement, 17 versus 21.3% (OR = 1.36; P < 0.05). CONCLUSIONS: The results
      suggest that the participation in the competition could delay the onset of
      smoking in adolescence.

PMID- 12202065
TI  - Assessment of feasibility of workplace health promotion.
AB  - BACKGROUND: A simple empirically based method for assessment of the feasibility
      of workplace health promotion programs is described, focusing on cancer hazards
      (lifestyles, workplace hazards, deficient early detection). The basic components
      of feasibility are addressed: extent of hazards; needs of employees for hazard
      reduction and acceptability of WHP; and social context. METHODS: The procedure
      consists of six modules: guidelines on feasibility assessment; employee
      questionnaire; interview checklists for probing attitudes of management and
      partners (social context); data form; debriefing; and assessment of feasibility.
      Pretesting was completed in 16 workplace communities representing industry,
      construction, transport, telecommunications, health care, lodging and catering,
      teaching, and municipality jobs in five countries; a total of 1,085 subjects
      completed the employee questionnaire on health hazards, needs, and acceptability.
      RESULTS: The method demonstrated its utility in obtaining and summarizing the
      necessary data. Feasibility was assessed for the 16 test communities. CONCLUSION:
      The procedure can be customized; it has a high degree of face validity or
      understandability, and it is applicable in a wide variety of settings.

PMID- 12202067
TI  - Cost-effectiveness of treatment options for prevention of rheumatic heart disease
      from Group A streptococcal pharyngitis in a pediatric population.
AB  - BACKGROUND: We set out to examine which treatment option available in the United
      States was most cost-effective in treating children with endemic group A
      streptococcal pharyngitis to prevent rheumatic heart disease. METHODS: Cost
      effectiveness was calculated from the societal perspective and expressed in cases
      of rheumatic heart disease prevented annually in the U.S. pediatric population
      aged 5 to 17 based on U.S. Census data. We used a decision-analysis model to
      assess the cost-effectiveness of five treatment options for patients with
      pharyngitis: (1) "treat all," (2) "treat none," (3) "rapid test," where only
      patients with a positive rapid antigen test are treated, (4) "culture," where
      only patients with a positive throat culture are treated, and (5) "rapid test
      with culture" or (RTCX), where confirmatory cultures are used on patients with
      negative rapid tests. Cost data were gathered from existing empirical data or
      estimated. We performed sensitivity analyses of the antigen test sensitivity and
      antibiotic effectiveness and examined whether changes in these variables would
      alter our outcome. RESULTS: The "rapid test" was the most cost-effective option.
      Using "rapid tests" prevented 85 cases of rheumatic heart disease annually and
      cost society $727,000 per case prevented. Performing throat cultures instead of
      "rapid tests" would pick up an additional 11 cases of rheumatic heart disease but
      would cost $13.7 million for each of these additional cases prevented. The
      current standard of using throat cultures as a confirmatory test on patients with
      a negative "rapid" test would detect an additional 21 cases of rheumatic heart
      disease but cost society an additional $8 million per case prevented.
      CONCLUSIONS: To reduce the incidence of rheumatic heart disease cost-effectively,
      the management of pediatric pharyngitis may best be accomplished by using antigen
      testing. The added costs associated with the remaining treatment options may not
      be justified, especially, as the sensitivity of the antigen tests continues to
      improve and closely approaches the sensitivity of the practice standard, throat
      culture.

PMID- 12202068
TI  - The relationship between temporal changes in blood pressure and changes in
      cognitive function: atherosclerosis risk in communities (ARIC) study.
AB  - BACKGROUND: Although previous epidemiological studies have reported that
      hypertension is a major risk factor for decline in brain perfusion and atrophy,
      which are known to be related to cognitive decline, the impact of temporal
      changes in blood pressure on age-related cognitive declines has not been
      assessed. METHODS: The present study evaluates changes in blood pressure and
      cognitive decline over a 6-year period in the Atherosclerosis Risk in Communities
      (ARIC) Study. This report is based on 8,058 men and women aged 48-67 years
      examined in the second (1990-92), and fourth (1996-98) ARIC cohort visits.
      Changes between these visits were measured in hypertension status and three
      cognitive function tests: Delayed Word Recall (DWR), the Digit Symbol Subtest of
      the Wechsler Adult Intelligence Scale-Revised (DSS/WAIS-R), and the Word Fluency
      (WF). Adjusted mean differences in cognitive function were compared among five
      categories of hypertension status by using linear regression modeling. RESULTS:
      In the present study, older subjects with uncontrolled hypertension had a
      significantly larger mean DSS/WAIS-R score decline than normotensive subjects.
      Although other cognitive declines did not achieve statistical significance, both
      cross-sectional and change analysis suggested that partially controlled or
      uncontrolled hypertension is associated with a less favorable cognitive profile,
      particularly when considering results of the DSS and the WF tests. CONCLUSIONS:
      The present study results provide some support to the hypothesis that
      hypertension status changes over 6 years in individuals initially aged 48-67
      years are related to cognitive changes.

PMID- 12202069
TI  - Do the elderly benefit from annual physical examination? An example from
      Kaohsiung City, Taiwan.
AB  - BACKGROUND: This study evaluates the impact of free annual health examinations on
      survival of elderly (> or =65 years of age) residents in Kaohsiung City, Taiwan.
      METHODS: A stratified random sample scheme was used in each of the 11 districts
      of Kaohsiung City. A total of 1,193 elderly people were selected and interviewed
      in 1993; deaths and results of health check-ups were recorded through 1998.
      RESULTS: While over 50% of the subjects received at least one health examination
      between 1993 and 1998, only 18% received three or more. Most (60%) subjects who
      received examinations in a given year also received examinations the subsequent
      year; most (over 70%) who did not receive examinations in a given year did not
      receive check-ups the following year. Cox proportional hazards model showed that
      those who utilized the examination service had better survival probability than
      those who did not, given the same age, sex, education, marital status, living
      arrangements, and number of chronic diseases at baseline: The relative risk (RR)
      of mortality for those who ever utilized the health examination service was 0.50
      (P < 0.0001). CONCLUSIONS: Elderly subjects who received annual health
      examinations had lower mortality than those who did not. This finding should be
      interpreted cautiously, however, as the difference in survival may reflect better
      general health behaviors among those who participated in the program.

PMID- 12202070
TI  - An assessment of factors related to tumor thickness and delay in diagnosis of
      melanoma in southern Italy.
AB  - BACKGROUND: Since survival of patients with melanoma is strongly correlated with
      the Breslow tumor thickness of the primary lesion, factors that influence stage
      at diagnosis and delay in diagnosis are considered to be crucial. To test the
      relationship between tumor thickness and some social and clinical variables
      (including diagnosis/treatment delay) and the relationship between the
      diagnosis/treatment delay and some clinical variables, we analyzed data on 530
      patients with melanoma from our Institute. METHODS: In the analysis, Breslow
      tumor thickness was categorized into two categories (< or =1.49, > or =1.5).
      Three time intervals were examined to evaluate diagnostic delay: patient delay,
      time from first symptom to seeking medical advice; medical delay, time from first
      medical consultation to hospital admission; total delay, time from first symptom
      to resection. The variables evaluated in the analysis were: age at diagnosis,
      education, occupational status, first symptom, visibility of tumor, anatomic
      site, and physician who made the initial diagnosis. RESULTS: A significant risk
      of having a Breslow tumor thickness > or =1.5 mm was noted in patients who had a
      low level of education (odds ratio 3.0, 95% confidence interval 1.9-5.0) or who
      were unemployed (odds ratio 1.7, 95% confidence interval 1.1-2.8). With respect
      to patient delay, a delay >3 months for anatomic locations visible to patients
      was associated with significant risk (odds ratio 1.7, 95% confidence interval 1.1
      2.6); with respect to medical delay, a delay >3 months was associated with a
      higher risk in patients examined by a dermatologist (odds ratio 2.0, 95%
      confidence interval 1.2-3.4). CONCLUSIONS: Our results clearly indicate that in
      Southern Italy poorly educated and unemployed subjects are at risk of being
      diagnosed at a more advanced stage, and admission to an oncological hospital
      causes a delay (waiting list) in the time interval related to the doctor (medical
      delay).

PMID- 12202071
TI  - Rapid identification of Wilson's disease carriers by denaturing high-performance
      liquid chromatography.
AB  - BACKGROUND: Wilson's disease is an autosomal recessive disorder characterized by
      decreased biliary copper excretion and reduced copper incorporation into
      ceruloplasmin. The disease gene ATP7B maps to chromosome 13q14.3, contains 21
      exons, and encodes a copper-transporting P-type ATPase. ATP7B mutations are
      scattered over the entire gene, and scanning methods to detect mutation carriers
      are in demand. We have tested the usefulness of denaturing high-performance
      liquid chromatography for mutation detection in Wilson's disease. METHODS:
      Genomic DNA from five Sardinian Wilson's disease families (32 individuals, 8
      patients) was subjected to polymerase chain reactions for ATP7B exons 2-21 and
      the 5' untranslated region. PCR products were analyzed by chromatography and by
      direct sequencing. RESULTS: Three disease-causing mutations and seven sequence
      variants were detected by chromatography. Five patients were homozygotes for 
      441/-427del, and three were compound heterozygotes for V1146M plus 1512-13insT
      (N505X) and for -441/-427del plus V1146M, respectively. Eighteen unaffected
      individuals were mutation carriers. Sequence variants comprised V290V, A406S,
      L456V, R832K, A1140V, the novel K952R, and T991T. The novel intronic IVS18+6c>t
      change escaped detection by chromatography. CONCLUSIONS: Denaturing high
      performance liquid chromatography is a dependable tool for ATP7B screening that
      is superior to traditional haplotyping. This method allows for fast, sensitive,
      and specific mutation detection and identification of carriers in Wilson's
      disease families.

PMID- 12202072
TI  - Wheeling Walks: a community campaign using paid media to encourage walking among
      sedentary older adults.
AB  - BACKGROUND: Mass media may effect communitywide changes in health awareness,
      attitude, and behavior, but the approach remains unproven for physical activity.
      METHODS: Wheeling Walks promoted walking among sedentary 50- to 65-year-old
      adults in a West Virginia city of 31,420 people. This quasi-experimental
      communication intervention used theory of planned behavior and transtheoretical
      model constructs to change behavior by promoting 30 min of daily walking through
      paid media, public relations, and public health activities. Impact was determined
      by pre- and postintervention telephone surveys with 719 adults in the
      intervention community and 753 adults in the comparison community and
      observations of walkers at 10 community sites. RESULTS: Behavior observation
      showed a 23% increase in the number of walkers in the intervention community
      versus no change in the comparison community (OR = 1.31, 95% CI = 1.14-1.50).
      Thirty-two percent (32.2) of the baseline sedentary population in the
      intervention community reported meeting the CDC/ACSM/Surgeon General
      recommendation for moderate-intensity physical activity by walking at least 30
      min at least five times per week versus 18.0% in the comparison community (OR =
      2.12, 95% CI = 1.41-2.24). The intervention community also realized a pre to post
      increase in positive stage change (P < 0.001). CONCLUSIONS: This theory-based
      mass media campaign demonstrated increases in those meeting the recommended
      standard for moderate-intensity physical activity through walking and significant
      positive stage change.

PMID- 12202073
TI  - Effectiveness of a clinic-based strategy for implementing the AHRQ Smoking
      Cessation Guideline in primary care.
AB  - BACKGROUND: The Agency for Healthcare Research and Quality Smoking Cessation
      Practice Guideline recommends systematic assessment of smoking status and
      counseling of smokers at every visit, but the actual effectiveness of the
      guideline in primary care practice is unknown. METHODS: We conducted a
      nonrandomized, controlled before-after trial of a guideline-derived intervention
      that includes routine identification and brief counseling of smokers by nurses
      and medical assistants, coupled with free nicotine replacement therapy (NRT) and
      telephone counseling of those smokers who are willing to make a quit attempt, and
      feedback on performance of guideline-recommended activities. The intervention was
      pilot tested at 1 family practice (FP) clinic over a 2-month period; patterns of
      usual care were observed concurrently at four control FP clinics. We obtained
      exit interviews of 651 consecutive adult smokers who presented for routine,
      nonemergency care. Abstinence (7-day point prevalence) was determined by
      telephone interview during 6-month follow-up. RESULTS: Concordance with
      guidelines was significantly greater for all recommended actions at the test site
      during the intervention versus baseline (P < or = 0.05). Significantly more
      intervention versus baseline patients at the test site reported abstinence at 2
      month follow-up (21 vs. 4%, P = 0.0004), and more patients tended to be abstinent
      at 6-month follow-up (21 vs. 11%, P = 0.08). No significant differences in 2- or
      6-month quit rates between intervention and baseline patients were observed at
      the control sites. CONCLUSIONS: Implementation of a guideline-driven smoking
      cessation intervention that focuses primarily on smokers who are interested in
      making a quit attempt is associated with increased abstinence in primary care
      practice.

PMID- 12202074
TI  - Integration of multiple motion vectors over space: an fMRI study of transparent
      motion perception.
AB  - Visual scenes are frequently composed of objects that move in different
      directions. To segment such scenes into distinct objects or image planes, local
      motion cues have to be evaluated and integrated according to criteria of global
      coherence. When several populations of coherently moving random dots penetrate
      each other, the visual system tends to assign them to different planes-perceived
      as transparent motion. This process of integration was studied by changing the
      angle of motion trajectories with which groups of dots penetrate each other or by
      varying the spatial constellation of dots moving in opponent directions.
      Psychophysical testing revealed that stimuli providing almost identical local
      motion cues could be perceived in three very different ways: (1) as a matrix of
      stationary flickering dots, (2) as a single surface of coherently moving dots,
      and (3) as two transparent dot matrices moving in different directions.
      Behaviorally controlled functional magnetic resonance imaging (fMRI) was used to
      identify brain regions that contribute to the integration of local motion cues
      into coherently moving surfaces. Activation of the human motion complex (hMT+/V5)
      and of areas in the fusiform gyrus (FG) as well as in the intraparietal sulcus
      (IPS-occ) was correlated with the perception of coherent motion and especially
      hMT+/V5 took a central role in differentiating transparent motion from single
      surface coherent motion.

PMID- 12202075
TI  - A parametric study of mental spatial transformations of bodies.
AB  - TWO CLASSES OF MENTAL SPATIAL TRANSFORMATION CAN BE DISTINGUISHED: Object-based
      spatial transformations are imagined movements of objects; and egocentric
      perspective transformations are imagined movements of one's point of view. The
      hypothesis that multiple neural systems contribute to these mental imagery
      operations was tested with functional MRI. Participants made spatial judgments
      about pictures of human bodies, and brain activity was analyzed as a function of
      the judgment required and the time taken to respond. Areas in right temporal,
      occipital and parietal cortex and the medial superior cerebellum appear to be
      differentially involved in object-based spatial transformations. Additionally,
      midline structures and lateral parietal cortex were found to decrease in activity
      during the spatial reasoning tasks, independently of the judgment required or of
      the latency of response. The results are discussed in terms of a model of spatial
      reasoning that postulates specialized subsystems for performing object-based and
      egocentric perspective image transformations.

PMID- 12202076
TI  - Neural correlates of visual-motion perception as object- or self-motion.
AB  - Both self-motion and objects moving in our visual field generate visual motion by
      displacing images on the retina. Resolving this ambiguity may seem effortless but
      large-field visual-motion stimuli can yield perceptual rivalry between the real
      percept of object-motion and the illusory percept of self-motion (vection). We
      used functional magnetic resonance imaging to record brain activity in human
      observers exposed to constant-velocity roll-motion. This stimulus induced
      responses in areas reaching from calcarine to parieto-occipital and to ventral
      and lateral temporo-occipital cortex and the anterior insula. During vection,
      early motion-sensitive visual areas and vestibular parieto-insular cortex
      deactivated, whereas higher-order parieto- and temporo-occipital areas known to
      respond to optical flow retained identical activity levels. Within this sustained
      response, these latter areas displayed transient activations in response to each
      perceptual switch as identified in event-related analyses. Our results thus show
      that these areas are responsive to the type of visual motion stimulus and highly
      sensitive to its perceptual bistability. The only region to be more active during
      perceived self-motion was in, or close to, the cerebellar nodulus. This
      activation may correspond to the gain increase of torsional optokinetic nystagmus
      during vection and/or to changes in sensory processing related to the rotational
      percept. In conclusion, we identified neural correlates of perceiving self-motion
      from vision alone, i.e., in the absence of confirmatory vestibular or
      proprioceptive input. These functional properties preserve the organism's ability
      to move accurately in its environment by relying on visual cues under conditions
      when the other spatial senses fail to provide such information.

PMID- 12202077
TI  - From perception to sentence comprehension: the convergence of auditory and visual
      information of language in the left inferior frontal cortex.
AB  - We used functional magnetic resonance imaging (fMRI) to characterize cortical
      activation associated with sentence processing, thereby elucidating where in the
      brain auditory and visual inputs of words converge during sentence comprehension.
      Within one scanning session, subjects performed three types of tasks with
      different linguistic components from perception to sentence comprehension:
      nonword (N(AV); auditory and visual), phrase (P; either auditory or visual), and
      sentence (S; either auditory or visual) tasks. In a comparison of the P and N(AV)
      tasks, the angular and supramarginal gyri showed bilateral activation, whereas
      the inferior and middle frontal gyri showed left-lateralized activation. A
      comparison of the S and P tasks, together with a conjunction analysis, revealed a
      ventral region of the left inferior frontal gyrus (F3t/F3O), which was sentence
      processing selective and modality-independent. These results unequivocally
      demonstrated that the left F3t/F3O is involved in the selection and integration
      of semantic information that are separable from lexico-semantic processing.

PMID- 12202078
TI  - Cortical systems associated with covert music rehearsal.
AB  - Musical representation and overt music production are necessarily complex
      cognitive phenomena. While overt musical performance may be observed and studied,
      the act of performance itself necessarily skews results toward the importance of
      primary sensorimotor and auditory cortices. However, imagined musical performance
      (IMP) represents a complex behavioral task involving components suited to
      exploring the physiological underpinnings of musical cognition in music
      performance without the sensorimotor and auditory confounds of overt performance.
      We mapped the blood oxygenation level-dependent fMRI activation response
      associated with IMP in experienced musicians independent of the piece imagined.
      IMP consistently activated supplementary motor and premotor areas, right superior
      parietal lobule, right inferior frontal gyrus, bilateral mid-frontal gyri, and
      bilateral lateral cerebellum in contrast with rest, in a manner distinct from
      fingertapping versus rest and passive listening to the same piece versus rest.
      These data implicate an associative network independent of primary sensorimotor
      and auditory activity, likely representing the cortical elements most intimately
      linked to music production.

PMID- 12202079
TI  - Volitional control of autonomic arousal: a functional magnetic resonance study.
AB  - Electrodermal activity reflects autonomic sympathetic innervation of dermal sweat
      glands providing an index of emotion-related bodily states of arousal. Relaxation
      techniques, which are facilitated by external (bio)feedback of electrodermal
      activity, can be used by trained subjects to actively control bodily and
      emotional arousal. Biofeedback relaxation provides an experimental model to
      explore neural mechanisms contributing to emotional representations and
      intentional autonomic control. We used functional magnetic resonance imaging
      (fMRI) to explore neural mechanisms contributing to integration of volitional
      intent, self-representation, and autonomic states of arousal, embodied within
      performance of a biofeedback relaxation exercise. Data were obtained from 17
      subjects to assess brain activity during relaxation in which a visual index of
      electrodermal arousal was modulated by accuracy (addition of random "noise") or
      sensitivity (by scalar adjustments of feedback). A central matrix of cortical,
      subcortical and brainstem autonomic centres was activated during biofeedback
      relaxation, as well as regions that mediate visual and somatesthetic
      representations and executive control. Anterior cingulate, amygdala, and insula
      activity was modulated by task manipulations that increased demand on processing
      interoceptive representations, while variation in anterior insula activity
      reflected an interaction between accuracy and sensitivity of feedback. These
      findings identify neural substrates that support integration of perceptual
      processing, interoception, and intentional modulation of bodily states of
      arousal.

PMID- 12202080
TI  - A blueprint for target motion: fMRI reveals perceived sequential complexity to
      modulate premotor cortex.
AB  - The execution of movements that are guided by an increasingly complex target
      motion is known to draw on premotor cortices. Whole-brain functional magnetic
      resonance imaging was used to investigate whether, in the absence of any
      movement, attending to and predicting increasingly complex target motion also
      rely on premotor cortices. Complexity was varied as a function of number of
      sequential elements and amount of dynamic sequential trend in a pulsing target
      motion. As a result, serial prediction caused activations in premotor and
      parietal cortices, particularly within the right hemisphere. Parametric analyses
      revealed that the right ventrolateral premotor cortex and the right anterior
      intraparietal sulcus were the only areas that, in addition, covaried positively
      with both behavioral and physical measures of sequential complexity. Further
      areas that covaried positively with increasing task difficulty reflected
      influences of both number and trend manipulation. In particular, increasing
      element number drew on dorsal premotor and corresponding posterior intraparietal
      regions, whereas increasing trend drew on the visual motion area and area V4. The
      present findings demonstrate that premotor involvement directly reflects
      perceptual complexity in attended and predicted target motion. It is suggested
      that when we try to predict how a target will move, the motor system generates a
      "blueprint" of the observed motion that allows potential sensorimotor
      integration. In the absence of any motor requirement, this blueprint appears to
      be not a by-product of motor planning, but rather the basis for target motion
      prediction.

PMID- 12202081
TI  - Comparison of minimum current estimate and dipole modeling in the analysis of
      simulated activity in the human visual cortices.
AB  - Magnetoencephalographic(MEG) data are typically interpreted using source models
      because of the nonunique inverse problem. Although single current dipoles,
      adequately representing local active areas, can be identified accurately,
      multiple and overlapping sources form a challenge for MEG modeling. We tested the
      performances of multidipole modeling and minimum current estimate (MCE) in the
      analysis of complicated source configurations. Simulated current sources were
      placed to physiologically meaningful areas of the human visual cortices. Ten
      volunteers from the laboratory staff analyzed four different simulations with
      both dipole modeling and MCE without prior information of the sources. In
      general, the same sources were found using both modeling methods. The subjects
      tended to report more false sources with MCE than with dipole model, in part due
      to their inexperience with the method. Dipole model was more accurate than MCE
      both in time and space for nonsimultaneous sources but both methods performed
      similarly when sources overlapped in time. For all source configurations,
      considerably smaller source amplitudes were reported with MCE than with dipole
      model.

PMID- 12202082
TI  - Physiological mapping of human auditory cortices with a silent event-related fMRI
      technique.
AB  - Cortical field boundaries of sensory areas can be physiologically defined. The
      delineation of the human auditory cortical architecture remains incomplete. Here
      we used systematic variation of pitch and duration of sinusoidal tones to define
      auditory cortical fields along Heschl's gyrus with a silent, event-related fMRI
      scanning technique that allowed us to determine spatially small shifts of
      neuronal responses. Thus, we were able to establish higher-resolution tonotopic
      maps. Acoustic intervals of two octaves correspond to an average 2-mm anatomical
      distance along Heschl's gyrus. We also demonstrate that one tonotopic map with a
      medio-lateral low- to high-frequency gradient is located on the lateral half of
      Heschl's gyrus, which might correspond to field R in primates. Furthermore, we
      studied cortical responses to brief (50-ms) transients with fMRI and demonstrate
      that silent, event-related fMRI is capable of measuring significant blood oxygen
      level-dependent effect to such brief events in the acoustic domain. Our results
      add to current knowledge on the number and precise localization of multiple
      tonotopic maps in human auditory cortex. More specifically, they support the
      hypothesis that there may be two primary auditory cortical fields with mirror
      tonotopic organization on Heschl's gyrus in man.

PMID- 12202083
TI  - Right-hemispheric organization of language following early left-sided brain
      lesions: functional MRI topography.
AB  - Left-hemispheric (LH) brain lesions acquired early in life can induce language
      organization in the undamaged right hemisphere (RH). This study addresses the
      anatomical correlates of language processing in the RH of such individuals. Five
      hemiparetic patients with left periventricular brain lesions of pre- and
      perinatal origin were included, in whom fMRI during a word generation task had
      yielded predominantly RH activation; five age- and sex-matched healthy right
      handers served as controls. The patterns of activation in the RH of patients
      showed a striking similarity with the LH patterns of the normal controls, and
      voxel-wise comparison failed to detect significant differences. This demonstrates
      that in patients with early LH damage, RH recruitment for language occurs in
      brain areas homotopic to the LH regions involved in language processing under
      normal circumstances.

PMID- 12202084
TI  - Filtering of distractors during visual search studied by positron emission
      tomography.
AB  - We investigated the sensitivity of brain areas to the presence of filtering
      operations during overt visual search in crowded displays. Task conditions
      involved either visual search or predetermined simple eye movements for the
      detection of target digits. Furthermore, visual displays either contained letter
      foils that required filtering or contained only target digits. Brain imaging
      using positron emission tomography showed extensive overlap between areas
      involved in overt visual search and eye movements. Selective filtering of foils
      affected visual processing in ventral areas associated with object recognition
      and in primary visual cortex.

PMID- 12202085
TI  - On the effects of spatial filtering--a comparative fMRI study of episodic memory
      encoding at high and low resolution.
AB  - The effects of spatial filtering in functional magnetic resonance imaging were
      investigated by reevaluating the data of a previous study of episodic memory
      encoding at 2 x 2 x 4-mm(3) resolution with use of a SPM99 analysis involving a
      Gaussian kernel of 8-mm full width at half maximum. In addition, a multisubject
      analysis of activated regions was performed by normalizing the functional images
      to an approximate Talairach brain atlas. In individual subjects, spatial
      filtering merged activations in anatomically separated brain regions. Moreover,
      small foci of activated pixels which originated from veins became blurred and
      hence indistinguishable from parenchymal responses. The multisubject analysis
      resulted in activation of the hippocampus proper, a finding which could not be
      confirmed by the activation maps obtained at high resolution. It is concluded
      that the validity of multisubject fMRI analyses can be considerably improved by
      first analyzing individual data sets at optimum resolution to assess the effects
      of spatial filtering and minimize the risk of signal contamination by
      macroscopically visible vessels.

PMID- 12202086
TI  - T(2)(*) dependence of low frequency functional connectivity.
AB  - Resting state low frequency (<0.08 Hz) fluctuations in MR timecourses that are
      temporally correlated between functionally related areas have been observed in
      recent studies. These fluctuations have been assumed to arise from spontaneous
      blood oxygenation level-dependent (BOLD) oscillations. This work examines the
      T(2)(*) characteristics of the low frequency fluctuations (functional
      connectivity) and compares them to those of task activation induced signal
      changes. Multi-echo spiral data were fit using a mono-exponential decay model to
      generate T(2)(*) and intensity (I(0)) parameter timecourses. Resultant
      correlation maps show that both functional connectivity and BOLD activation
      modulate T(2)(*), not I(0). Regression analysis also finds that both have a
      linear dependence on echo time. Thus, functional connectivity and task activation
      MR signal changes appear to arise from the same BOLD-related origins.

PMID- 12202087
TI  - White matter glucose metabolism during intracortical electrostimulation: a
      quantitative [(18)F]Fluorodeoxyglucose autoradiography study in the rat.
AB  - [(18)F]Fluorodeoxyglucose (FDG) autoradiography was used to analyze the effects
      of intracortical electrostimulation on local cerebral metabolic rate for glucose
      (LCMRglu). The hindleg area in rat brains was electrically stimulated with
      different frequencies (0, 0.1, 0.25, 0.5, 0.75, 1 stimulus trains per second, two
      animals per condition). The major result was a strong positive correlation
      between stimulation frequency and LCMRglu in the callosal fibers originating in
      the stimulated cortical area. At the highest stimulation frequency callosal
      LCMRglu was 50.01 micromol/min/100 g compared to 27.87 micromol/min/100 g at
      baseline. LCMRglu in gray and white matter control areas was stable across
      conditions. Direct injection of FDG in the stimulated cortex failed to produce
      increased callosal uptake, excluding the possibility that FDG uptake in the
      corpus callosum is related to axonal diffusion. Although several previous
      autoradiographic studies have demonstrated alterations in LCMRglu in white
      matter, correlations between neural activity and LCMRglu have never been
      explicitly addressed. Changes in white matter metabolism most likely reflect
      changes of electrical fiber activity and thus the presented results bear
      important implications for brain imaging studies.

PMID- 12202088
TI  - Combining fMRI with a pharmacokinetic model to determine which brain areas
      activated by painful stimulation are specifically modulated by remifentanil.
AB  - We present a method for investigating the dynamic pharmacological modulation of
      pain-related brain activity, measured by BOLD-contrast fMRI. Noxious thermal
      stimulation was combined with a single infusion and washout of remifentanil, a
      short-acting opioid analgesic agent. The temporal profile of the effect site
      concentration of remifentanil, estimated from a pharmacokinetic model, was
      incorporated into a linear model of the fMRI data. The methodology was tested in
      nine healthy male subjects. During each imaging session the subjects received
      noxious thermal stimulation to the back of the left hand, prior to infusion,
      during infusion to a remifentanil effect site concentration of 1.0 ng/ml, and
      during washout of the remifentanil. Infusions were repeated with saline.
      Remifentanil-induced analgesia was confirmed from subjective pain intensity
      scores. Pain-related brain activity was identified in a matrix of regions using a
      linear model of the transient BOLD responses to noxious stimulation. Of those
      regions, there was a significant fractional reduction in the amplitude of the
      pain-related BOLD response in the insular cortex contralateral to the stimulus,
      the ipsilateral insular cortex, and the anterior cingulate cortex. Statistical
      parametric mapping of the component of pain-related BOLD responses that was
      linearly scaled by remifentanil concentration confirmed the contralateral insular
      cortex as the pain-processing region most significantly modulated by remifentanil
      compared to saline. The mapping of specific modulation of pain-related brain
      activity is directly relevant for understanding pharmacological analgesia. The
      method of examining time-dependent pharmacological modulation of specific brain
      activity may be generalized to other drugs that modulate brain activity other
      than that associated with pain.

PMID- 12202089
TI  - In vivo detection of striatal dopamine release during reward: a PET study with
      [(11)C]raclopride and a single dynamic scan approach.
AB  - A new simple method is proposed to detect, using PET and [(11)C]raclopride,
      changes in striatal extracellular dopamine concentration during a rewarded
      effortful task. This approach aimed to increase the sensitivity in detection of
      these effects. It requires a single-dynamic PET study and combines the classic
      kinetic compartmental model with the general linear model of SPM to provide
      statistical inference on changes in [(11)C]raclopride time-activity curve due to
      endogenous dopamine release during two short periods of activation. Kinetic
      simulations predicted that 100% dopamine increase during two 5-min periods
      starting at 30 and 60 min after the injection can be detected. Moreover the
      effects of dopamine release on the [(11)C]raclopride time-activity-curve are
      different from those induced by CBF increase. These simulated curves were used to
      construct the statistical linear model and to test voxel-by-voxel in healthy
      subjects the hypothesis that dopamine is released in the ventral striatum during
      periods of unexpected monetary gains, but not during periods of unexpected
      monetary loss. The experimental results are in line with the expected results
      although the amplitude of the effects due to dopamine release is moderate. The
      advantages and the limits of this method as well as the relevance of the results
      for dopamine involvement in reward processing are discussed.

PMID- 12202090
TI  - Neuronal specificity of acupuncture response: a fMRI study with
      electroacupuncture.
AB  - Recently, neuronal correlates of acupuncture stimulation in human brain have been
      investigated by functional neuroimaging. The preliminary findings suggest that
      acupuncture at analgesic points involves the pain-related neuromatrix and may
      have acupoint-brain correlation. Although multiple models of control stimulations
      have been applied to address the specificity of the needling effect clinically,
      their impacts have not been evaluated by functional neuroimaging. With the
      advantage of objective parameter setting, electroacupuncture (EA) was used in
      this study to devise three distinct controls for real EA, i.e., mock EA (no
      stimulation), minimal EA (superficial and light stimulation), and sham EA (same
      stimulation as real EA) applied at nonmeridian points. Fifteen healthy volunteers
      received real EA at analgesic point Gallbladder 34 (Yanglinquan), sham EA, and
      one of either mock EA or minimal EA over the left leg in counter-balanced orders.
      Multisubject analysis showed that sham EA and real EA both activated the reported
      distributed pain neuromatrix. However, real EA elicited significantly higher
      activation than sham EA over the hypothalamus and primary somatosensory-motor
      cortex and deactivation over the rostral segment of anterior cingulate cortex. In
      the comparison of minimal EA versus mock EA, minimal EA elicited significantly
      higher activation over the medial occipital cortex. Single-subject analysis
      showed that superior temporal gyrus (encompassing the auditory cortex) and medial
      occipital cortex (encompassing the visual cortex) frequently respond to minimal
      EA, sham EA, or real EA. We concluded that the hypothalamus-limbic system was
      significantly modulated by EA at acupoints rather than at nonmeridian points,
      while visual and auditory cortical activation was not a specific effect of
      treatment-relevant acupoints and required further investigation of the underlying
      neurophysiological mechanisms.

PMID- 12202091
TI  - Cerebral lobes in autism: early hyperplasia and abnormal age effects.
AB  - Metabolic, functional, behavioral, and histologic studies suggest that the
      structure of the cerebrum may be abnormal in autism. In a previous cross
      sectional study we found abnormal enlargement of cerebral cortex and cerebral
      white matter volumes in autistic 2- and 3-year-olds and abnormally slow rates of
      volume change across later ages. In the present study, we assessed whether these
      volume abnormalities are limited to particular cerebral regions or are pervasive
      throughout the cerebrum. We used magnetic resonance imaging (MRI) to quantify
      volumes of cerebral lobes (frontal, temporal, parietal, and occipital regions),
      using classic sulcal boundaries to define regions. We examined 38 boys with
      autism and 39 normal control boys between the ages of 2 and 11 years. Several
      regions showed signs of gray matter and white matter hyperplasia in 2- and 3-year
      old patients (as much as 20% enlargement), but there appeared to be an anterior
      to posterior gradient in the degree of hyperplasia. The frontal lobe showed the
      greatest enlargement while the occipital lobe was not significantly different
      from normal. Gray and white matter differences were not found in the older
      children. By examining the relationships between regional volumes and subject
      age, we found that frontal, temporal, and parietal white matter volumes, as well
      as frontal and temporal gray matter volumes, changed at significantly slower
      rates in autism patients than in controls across the 2- to 11-year-age range. For
      example, frontal lobe white matter volume increased by about 45% from 2-4 years
      of age to 9-11.5 years, but by only 13% in autistic patients. Mechanisms that
      might account for early hyperplasia are discussed as they might relate to the
      regional differences in degree of abnormality. For instance, possible influences
      of neurotrophic factors, or of abnormal afferent activity from other affected
      brain regions are considered.

PMID- 12202092
TI  - Tryptophan depletion effects on EEG and MEG responses suggest serotonergic
      modulation of auditory involuntary attention in humans.
AB  - Involuntary attention shifting, i.e., detecting and orienting to unexpected
      stimulus changes, may be altered at low brain serotonin (5-hydroxytryptamine; 5
      HT) levels. This was studied in 13 healthy subjects (21-30 years old; 6 females)
      by using a dietary challenge, acute tryptophan depletion (ATD), which decreases 5
      HT synthesis in the brain. Five hours after ingestion of either ATD or control
      mixture (randomized, double-blinded, crossover design), brain responses indexing
      involuntary attention were measured with simultaneous 64-channel
      electroencephalography (EEG) and 122-channel magnetoencephalography (MEG). During
      the measurement, the subjects were instructed to discriminate equiprobable 200-
      and 400-ms tones by pressing one of two buttons rapidly. Occasionally, the
      frequency of the tones changed (10% increase/decrease), causing involuntary
      attention shifting. ATD significantly lowered plasma tryptophan concentrations
      (total tryptophan decreased by 75%, free tryptophan decreased by 35%). As
      compared to the control condition, ATD reduced the amplitude of the deviant-tone
      N2 wave, including the overlapping mismatch negativity (MMN) and N2b
      subcomponents, which are suggested to reflect change detection in the brain. The
      EEG results were accompanied by a significant increase in the peak latency of the
      magnetic counterpart of MMN. However, no ATD effects were observed in P3 to task
      irrelevant frequency change. Reaction time (RT) to deviants per se was not
      significantly affected, but RT in trials succeeding the deviant-frequency tones
      was increased by ATD, which suggested impaired reorienting to the task-relevant
      activity. In conclusion, the results suggest that decreased level of central 5-HT
      function after ATD may decrease involuntary attention shifting to task-irrelevant
      sound changes and thus modulate resource allocation to the task-relevant
      activity.

PMID- 12202093
TI  - How much cortex can a vein drain? Downstream dilution of activation-related
      cerebral blood oxygenation changes.
AB  - The draining vein problem is recognized as one of the most severe constraints on
      the spatial resolution of BOLD contrast fMRI, used widely in imaging
      neuroscience. Changes in blood oxygenation arising from local brain activity
      related changes in blood flow propagate downstream in veins and can give rise to
      spurious activation at sites remote from neuronal activity. The geometry of the
      venous vasculature is quite regular in structure and is well depicted in
      photomicrographs. Quantitative analysis of this geometry, together with
      hydrodynamic considerations, permit upper bounds dependent on the area of
      cortical neuronal activity to be derived for the spatial extent of draining vein
      contamination. It is estimated that an activated cortical area of 100 mm(2) will
      generate an oxygenation change in venous blood that extends without dilution
      along the vein no more than 4.2 mm beyond the edge of the activated area. At
      greater distances along the draining vein this oxygenation change will be
      diluted. The model leads to a quantitative prediction of the functional form of
      this dilution.

PMID- 12202094
TI  - Multivariate model specification for fMRI data.
AB  - We present a general method-denoted MoDef-to help specify (or define) the model
      used to analyze brain imaging data. This method is based on the use of the
      multivariate linear model on a training data set. We show that when the a priori
      knowledge about the expected brain response is not too precise, the method allows
      for the specification of a model that yields a better sensitivity in the
      statistical results. This obviously relies on the validity of the a priori
      information, in our case the representativity of the training set, an issue
      addressed using a cross-validation technique. We propose a fast implementation
      that allows the use of the method on large data sets as found with functional
      Magnetic Resonance Images. An example of application is given on an experimental
      fMRI data set that includes nine subjects who performed a mental computation
      task. Results show that the method increases the statistical sensitivity of fMRI
      analyses.

PMID- 12202095
TI  - Orthographic/phonological facilitation of naming responses in the picture-word
      task: an event-related fMRI study using overt vocal responding.
AB  - In the picture-word interference task, naming responses are facilitated when a
      distractor word is orthographically and phonologically related to the depicted
      object as compared to an unrelated word. We used event-related functional
      magnetic resonance imaging (fMRI) to investigate the cerebral hemodynamic
      responses associated with this priming effect. Serial (or independent-stage) and
      interactive models of word production that explicitly account for picture-word
      interference effects assume that the locus of the effect is at the level of
      retrieving phonological codes, a role attributed recently to the left posterior
      superior temporal cortex (Wernicke's area). This assumption was tested by
      randomly presenting participants with trials from orthographically related and
      unrelated distractor conditions and acquiring image volumes coincident with the
      estimated peak hemodynamic response for each trial. Overt naming responses
      occurred in the absence of scanner noise, allowing reaction time data to be
      recorded. Analysis of this data confirmed the priming effect. Analysis of the
      fMRI data revealed blood oxygen level-dependent signal decreases in Wernicke's
      area and the right anterior temporal cortex, whereas signal increases were
      observed in the anterior cingulate, the right orbitomedial prefrontal,
      somatosensory, and inferior parietal cortices, and the occipital lobe. The
      results are interpreted as supporting the locus for the facilitation effect as
      assumed by both classes of theoretical model of word production. In addition, our
      results raise the possibilities that, counterintuitively, picture-word
      interference might be increased by the presentation of orthographically related
      distractors, due to competition introduced by activation of phonologically
      related word forms, and that this competition requires inhibitory processes to be
      resolved. The priming effect is therefore viewed as being sufficient to offset
      the increased interference. We conclude that information from functional imaging
      studies might be useful for constraining theoretical models of word production.

PMID- 12202096
TI  - The role of the dorsolateral prefrontal cortex: evidence from the effects of
      contextual constraint in a sentence completion task.
AB  - Although the prefrontal cortices, in particular the dorsolateral prefrontal
      cortex (DLPFC), have been examined in numerous imaging and neuropsychological
      studies, it has proved difficult to assign a specific function to this brain
      region. The aim of this study was therefore to delineate the function of the
      DLPFC first by using positron emission tomography with a word generation task and
      second by comparing these findings with a series of different circumstances in
      which the DLPFC is activated in association with response selection. Six healthy
      volunteers were presented with a sentence completion task based on the Hayling
      test. In each of two conditions, (A) response initiation and (B) response
      suppression, volunteers saw a sentence with the final word omitted. In condition
      A they had to provide a word that fitted at the end of the sentence and in
      condition B they had to provide a word that did not fit. The corpus of sentences
      used varied systematically in their level of contextual constraint, ranging from
      low to high. With all levels of constraint combined, significant greater
      activation was observed in the left DLPFC (BA46/9) under the suppression
      condition and in the medial orbitofrontal cortex (BA11) under the initiation
      condition. Under the high-constraint condition with both tasks combined,
      significant right middle temporal activity (BA21) was observed, whereas under low
      constraint, the left DLPFC was significantly activated. An interaction of task
      and constraint revealed that the left DLPFC was significantly more active in the
      suppression task at all levels of constraint, but only under the low-constraint
      conditions in the initiation task. The reaction time analyses mirrored the
      pattern of activity observed, with slower reaction times under conditions of
      suppression and under conditions of initiation with low constraint. By comparing
      these findings with other studies of response selection, we argue that the most
      likely single cognitive function of the DLPFC is to specify a set of responses
      suitable for a given task and to bias these for selection (sculpting the response
      space). This function resembles the biasing of competition between stimuli in the
      model of Desimone and Duncan and is analogous to the component of the Supervisory
      Attentional System that modulates the contention scheduling system.

PMID- 12202097
TI  - A robust transcortical profile scanner for generating 2-d traverses in
      histological sections of richly curved cortical courses.
AB  - Quantitative analysis of the cerebral cortex has become more important since
      neuroimaging methods have revealed many subfunctions of cortical regions that
      were thought to be typical for only one specific function. Furthermore, it is
      often unknown if a certain area may be subdivided observer independently into
      subareas. These questions lead to an analytical problem. How can we analyze the
      cytoarchitecture of the human cerebral cortex in a quantitative manner in order
      to confirm classical transition regions between distinct areas and to detect new
      ones. Scanning the cerebral cortex is difficult because it presents a richly
      curved course and sectioning always leads to partially nonperpendicular sectioned
      regions of the tissue. Therefore, different methods were tested to determine
      which of them are most reliable with respect to generating perpendicular
      testlines in the cerebral cortex. We introduce a new technique based on
      electrical field theory. The results of this technique are compared with those of
      conventional techniques. It was found that straight traverses generated by the
      electrodynamic model present significantly smaller intertraversal differences
      than the conventional approaches.

PMID- 12202098
TI  - Frontal lobe activation during object permanence: data from near-infrared
      spectroscopy.
AB  - The ability to create and hold a mental schema of an object is one of the
      milestones in cognitive development. Developmental scientists have named the
      behavioral manifestation of this competence object permanence. Convergent
      evidence indicates that frontal lobe maturation plays a critical role in the
      display of object permanence, but methodological and ethical constrains have made
      it difficult to collect neurophysiological evidence from awake, behaving infants.
      Near-infrared spectroscopy provides a noninvasive assessment of changes in oxy-
      and deoxyhemoglobin and total hemoglobin concentration within a prescribed
      region. The evidence described in this report reveals that the emergence of
      object permanence is related to an increase in hemoglobin concentration in
      frontal cortex.

PMID- 12202099
TI  - Motion and ballistocardiogram artifact removal for interleaved recording of EEG
      and EPs during MRI.
AB  - Artifacts generated by motion (e.g., ballistocardiac) of the head inside a high
      magnetic field corrupt recordings of EEG and EPs. This paper introduces a method
      for motion artifact cancellation. This method is based on adaptive filtering and
      takes advantage of piezoelectric motion sensor information to estimate the motion
      artifact noise. This filter estimates the mapping between motion sensor and EEG
      space, subtracting the motion-related noise from the raw EEG signal. Due to
      possible subject motion and changes in electrode impedance, a time-varying
      mapping of the motion versus EEG is required. We show that this filter is capable
      of removing both ballistocardiogram and gross motion artifacts, restoring EEG
      alpha waves (8-13 Hz), and visual evoked potentials (VEPs). This adaptive filter
      outperforms the simple band-pass filter for alpha detection because it is also
      capable of reducing noise within the frequency band of interest. In addition,
      this filter also removes the transient responses normally visible in the EEG
      window after echo planar image acquisition, observed during interleaved EEG/fMRI
      recordings. Our adaptive filter approach can be implemented in real-time to allow
      for continuous monitoring of EEG and fMRI during clinical and cognitive studies.

PMID- 12202100
TI  - A regression analysis study of the primary somatosensory cortex during pain.
AB  - Several functional imaging studies of pain, using a number of different
      experimental paradigms and a variety of reference states, have failed to detect
      activations in the somatosensory cortices, while other imaging studies of pain
      have reported significant activations in these regions. The role of the
      somatosensory areas in pain processing has therefore been debated. In the present
      study the left hand was immersed in painfully cold water (standard cold pressor
      test) and in nonpainfully cold water during 2 min, and PET-scans were obtained
      either during the first or the second minute of stimulation. We observed no
      significant increase of activity in the somatosensory regions when the painful
      conditions were directly compared with the control conditions. In order to better
      understand the role of the primary somatosensory cortex (S1) in pain processing
      we used a regression analysis to study the relation between a ROI (region of
      interest) in the somatotopic S1-area for the stimulated hand and other regions
      known to be involved in pain processing. We hypothesized that although no
      increased activity was observed in the S1 during pain, this region would change
      its covariation pattern during noxious input as compared to the control
      stimulation if it is involved in or affected by the processing of pain. In the
      nonpainful cold conditions widespread regions of the ipsilateral and
      contralateral somatosensory cortex showed a positive covariation with the
      activity in the S1-ROI. However, during the first and second minute of pain this
      regression was significantly attenuated. During the second minute of painful
      stimulation there was a significant positive covariation between the activity in
      the S1-ROI and the other regions that are known to be involved in pain
      processing. Importantly, this relation was significantly stronger for the insula
      and the orbitofrontal cortex bilaterally when compared to the nonpainful state.
      The results indicate that the S1-cortex may be engaged in or affected by the
      processing of pain although no differential activity is observed when pain is
      compared with the reference condition.

PMID- 12202101
TI  - Reduction of gradient acoustic noise in MRI using SENSE-EPI.
AB  - A new approach to reduce gradient acoustic noise levels in EPI experiments is
      presented. Using multichannel RF receive coils, combined with SENSE data
      acquisition and reconstruction, gradient slew-rates in single-shot EPI were
      reduced fourfold for rate-2 and ninefold for rate-3 SENSE. Multislice EPI
      experiments were performed on three different scanner platforms. With 3.4 mm in
      plane resolution, measuring 6 slices per second (12 slices with 2000 ms TR), this
      resulted in average sound pressure level reductions of 11.3 dB(A) and 16.5 dB(A)
      for rate-2 and rate-3 SENSE, respectively. BOLD fMRI experiments, using visually
      paced finger-tapping paradigms, showed no detrimental effect of the acoustic
      noise reduction strategy on temporal noise levels and t scores.

PMID- 12202102
TI  - Lid closure mimics head movement in fMRI.
AB  - Motion correction algorithms are commonly used to correct for involuntary head
      motions in fMRI. We found that lid closure increased signal intensity of the eyes
      by a factor of 1.6 to 2 in EPI-fMRI. If the eyes were included in the scanning
      volume, transitions from eyes open to eyes closed in darkness were regularly
      associated with erroneously detected head translations along the z-axis and head
      rotations around the x-axis in Talairach's coordinate system. These artefacts
      could be avoided by masking the eyes in the images during the estimation of
      movement parameters.

PMID- 12202103
TI  - Hyperscanning: simultaneous fMRI during linked social interactions.
AB  - "Plain question and plain answer make the shortest road out of most
      perplexities." Mark Twain-Life on the Mississippi. A new methodology for the
      measurement of the neural substrates of human social interaction is described.
      This technology, termed "Hyperscan," embodies both the hardware and the software
      necessary to link magnetic resonance scanners through the internet. Hyperscanning
      allows for the performance of human behavioral experiments in which participants
      can interact with each other while functional MRI is acquired in synchrony with
      the behavioral interactions. Data are presented from a simple game of deception
      between pairs of subjects. Because people may interact both asymmetrically and
      asynchronously, both the design and the analysis must accommodate this added
      complexity. Several potential approaches are described.

PMID- 12202104
TI  - Toxicity and immunogenicity of purified Haemophilus ducreyi cytolethal distending
      toxin in a rabbit model.
AB  - The cytolethal distending toxin of Haemophilus ducreyi (HdCDT) is a three
      component toxin that induces the arrest of the mammalian cell cycle in the G2
      phase. All of the individual gene products, CdtA, CdtB and CdtC, are required for
      toxic activity on cultured mammalian cells. The CdtB component alone exerts
      nuclease activity. The individual HdCDT components were purified by affinity
      chromatography or ion-exchange chromatography followed by gel-filtration. HdCDT
      was reconstituted and purified by the immobilization of a GST-CdtB fusion on a
      GSTrap column and the subsequent addition of cell sonicates from Escherichia coli
      recombinants that produced CdtA and CdtC. The purified HdCDT preparation
      contained all three CDT proteins, as detected by immuno-blotting, and had high
      cytotoxic activity (10(6)CPU/ml). Immunization of rabbits with the HdCDT complex
      and with the individual CdtA, CdtB and CdtC proteins elicited high titres of
      antibodies, as detected by ELISA. All of the immune sera had toxin-neutralizing
      activities. The pathological effects of the HdCDT complex were investigated in
      rabbits, since the proliferation of two rabbit cell lines, SIRC and RK-13, was
      inhibited by HdCDT. Intradermal injection of HdCDT (1, 10, 50 and 100microg
      protein) into naive rabbits resulted in dose-dependent skin reactions (erythema)
      about 24h after injection. Similar effects were not observed when the individual
      HdCDT proteins were injected. HdCDT injection into immune rabbits resulted in
      dose-dependent skin responses that were characterized by both erythema and
      oedema. Histological evaluation of the 24-h lesions in naive rabbits that were
      injected with HdCDT, revealed moderate levels of inflammatory cells, which were
      mainly granulocytes and macrophages, and dilatation of blood vessels. The skin
      reactions in HdCDT-injected immunized rabbits showed pronounced vascular changes
      and extensive infiltration of inflammatory cells, including eosinophils. All of
      the pathological changes healed after 3 days. In conclusion, purified HdCDT
      holotoxin is a complex of all three CDT proteins and all three components induce
      neutralizing antibodies when injected in rabbits. HdCDT causes dose-dependent
      pathologic skin reactions in both naive and immune rabbits, which is
      characterized by increased inflammatory responsiveness after each immunization.

PMID- 12202105
TI  - Infection and pathogenesis of a murine strain of Escherichia coli with
      genetically introduced Shiga toxin type I operon in conventional mice.
AB  - The pathogenic response elicited by Shiga toxin type I (Stx1)-producing
      Escherichia coli was studied using an E. coli strain BME5 obtained from the
      natural flora of the mouse and used on three different strains of mice. The
      recombinant strain BME5/Stx1 was prepared by introducing the gene for Stx1.
      Following an oral inoculation of 1.0x10(9)cfu of BME5/Stx1 faecal recovery of
      1.0x10(8)cfu/g faeces over 3 weeks was obtained. Neurologic signs as well as
      histopathological changes of the intestine and the kidneys were observed within 3
      days after infection and elevated serum cytokines including IL-1beta and TNF
      alpha were observed. Furthermore, the recombinant organisms were established in
      the intestine and showed exquisitely virulence when infected peritoneally in
      mice, while parent strain BME5 though colonized did not show any pathological
      changes. These results suggest that E. coli BME/Stx1 can colonize the mouse
      intestine under natural environment, and induced systemic neural changes and
      inflammation in the intestine and kidneys.

PMID- 12202106
TI  - Regulation of Staphylococcus aureus type 5 capsular polysaccharides by agr and
      sarA in vitro and in an experimental endocarditis model.
AB  - The expression of antiphagocytic polysaccharide capsules is an important
      pathogenetic step in establishing Staphylococcus aureus infections. Using a green
      fluorescent protein reporter gene (gfp) system, we examined the expression and
      genetic regulation of the cap5 promoter (capsular polysaccharide 5 genes) by two
      major global regulators of S. aureus (agr and sarA) in vitro and in a rabbit
      endocarditis model. In vitro, cap5 expression substantially increased during the
      post-exponential phase in parental, as well assarA mutant constructs. However,
      cap5 expression was greatly reduced in agr and agr/sarA double mutants. In the
      endocarditis model, the extent of cap5 expression in vegetations infected with
      the parental strain was substantially higher than that observed with the agr/sarA
      double mutants (P<0.05). Similar trends were noted in renal, but not splenic
      abscesses. Collectively, these data suggest that agr positively regulates cap5
      expression both in vitro and in vivo, while the contribution of sarA to cap5
      regulation, although modest, is readily discerned in vivo in agr minus
      background. In addition, the regulation ofcap5 expression by these global
      regulators may vary in distinct anatomic niches in vivo.

PMID- 12202107
TI  - Site-directed mutagenesis studies of the amino acid residue at position 412 of
      Escherichia coli TolC which is required for the activity.
AB  - The Escherichia coli TolC acts as a channel-tunnel in the transport of molecules
      across the outer membrane. We previously showed that the region extending from
      the 50th to the 60th amino acid residues from the carboxy terminus is involved in
      the transport activity of TolC. To clarify which amino acids are important to the
      activity, we mutated the gene coding these residues and examined the activity of
      the mutant TolCs. The results showed that leucine at position 412, the 60th amino
      acid residue from the carboxy terminal end, is important. Further mutational
      research on the residue suggested that TolC required a nonpolar amino acid
      residue at position 412 to express its activity.

PMID- 12202108
TI  - A model for estimating total parasite load in falciparum malaria patients.
AB  - We describe an age-structured mathematical model of the malaria parasite life
      cycle that uses clinical observations of peripheral parasitaemia to estimate
      population dynamics of sequestered parasites, which are hidden from the clinical
      investigator. First, the model was tested on parasite populations cultured in
      vitro, and was found to account for approximately 72% of the variation in that
      sub-population of parasites that would have been sequestered in vivo. Next, the
      model was applied to patients undergoing antimalarial therapy. Using individual
      data sets we found that although the model fitted the peripheral parasite curves
      very well, unique solutions for the fit could not be obtained; therefore, robust
      estimates of sequestered parasite dynamics remained unavailable. We conclude that
      even given detailed data on individual parasitaemia, estimates of sequestered
      numbers may be difficult to obtain. However, if data on individuals undergoing
      similar therapy are collected at equal time intervals, some of these problems may
      be overcome by estimating specific parameters over groups of patients. In this
      manner we estimated sequestered parasite density in a group of patients sampled
      at identical time points following antimalarial treatment. Using this approach we
      found significant relationships between changes in parasite density, age
      structure and temperature that were not apparent from the analysis of peripheral
      parasitaemia only.

PMID- 12202109
TI  - Group formation games with reappraisal.
AB  - The formation of a social group, such as the group of individuals sharing a
      territory, depends on the interaction between choices made by individuals to stay
      or disperse. The process can be modelled as a multi-player variant of the well
      known War of Attrition in evolutionary game theory, as shown by Blackwell (1997;
      J. Theor. Biol.189, 175-181). In this paper, we extend the set of strategies
      defined there by allowing reappraisal during the game. We give a formal analysis
      of the evolutionarily stable strategy, where one exists, and illustrate it with
      an example based on badger (Meles meles) territoriality. The results predict that
      group size will be well adapted to, and very sensitive to, the precise conditions
      under which the game is played, and give an indication of the potential for
      parent-offspring conflict.

PMID- 12202110
TI  - Dynamics between a predator and a prey switching two kinds of escape motions.
AB  - In nature, animals are classified into two large groups. Those that form the prey
      and that form the predator. A prey animal runs for its life when chased by a
      predatory animal. When prey animals escape from the chasing enemy, they generally
      use two types of evasive motion. Those are a straight-line escape motion and a
      zigzag-line escape motion. A fleeing prey switches between two types of evasive
      behavior in a manner depending on the predator's performance.I propose a
      mathematical model that expresses behaviors between a prey and a predator. This
      model brings that a straight-line escape motion is a better solution for an
      escape from a slow and far predator. On the other hand, an evasive motion for a
      near or fast enemy is a zigzag-line escape motion. This model suggests that
      animals have the best evasive strategy.

PMID- 12202111
TI  - "Living" under the challenge of information decay: the stochastic corrector model
      vs. hypercycles.
AB  - The combined problem of having a large genome size when the accuracy of
      replication was a limiting factor is probably the most difficult transition to
      explain at the late stages of RNA world. One solution has been to suggest the
      existence of a cyclically coupled system of autocatalytic and cross-catalytic
      molecular mutualists, where each member helps the following member and receives
      help from the preceding one (i.e., a "hypercycle"). However, such a system is
      evolutionarily unstable when mutations are taken into account because it lacks
      individuality. In time, the cooperating networks of genes should have been
      encapsulated in a cell-like structure. But once the cell was invented, it closely
      aligned genes' common interests and helped to reduce gene selfishness, so there
      was no need for hypercycles. A simple package of competing genes, described by
      the "stochastic corrector model" (SCM), could have provided the solution. Until
      now, there is no clear demonstration that the proposed mechanisms
      (compartmentalized hypercycles and the stochastic corrector model) do in fact
      solve the error threshold problem. Here, we present a Monte Carlo model to test
      the viability of protocell populations that enclose a hypercyclic (HPC) or a non
      hypercyclic (SCM) system when faced with realistic mutation rates before the
      evolution of efficient enzymic machinery for replication. The numerical results
      indicate that both systems are efficient information integrators and are able to
      overcome the danger of information decay in the absence of accurate replication.
      However, a population of SCM protocells can tolerate higher deleterious mutation
      rates and reaches an equilibrium mutational load lower than that in a population
      of HPC protocells.

PMID- 12202112
TI  - The dilemma of the selfish herd: the search for a realistic movement rule.
AB  - The selfish herd hypothesis predicts that aggregations form because individuals
      move toward one another to minimize their own predation risk. The "dilemma of the
      selfish herd" is that movement rules that are easy for individuals to follow,
      fail to produce true aggregations, while rules that produce aggregations require
      individual behavior so complex that one may doubt most animals can follow them.
      If natural selection at the individual level is responsible for herding behavior,
      a solution to the dilemma must exist. Using computer simulations, we examined
      four different movement rules. Relative predation risk was different for all four
      movement rules (p<0.05). We defined three criteria for measuring the quality of a
      movement rule. A good movement rule should (a) be statistically likely to benefit
      an individual that follows it, (b) be something we can imagine most animals are
      capable of following, and (c) result in a centrally compact flock. The local
      crowded horizon rule, which allowed individuals to take the positions of many
      flock-mates into account, but decreased the influence of flock-mates with
      distance, best satisfied these criteria. The local crowded horizon rule was very
      sensitive to the animal's perceptive ability. Therefore, the animal's ability to
      detect its neighbors is an important factor in the dynamics of group formation.

PMID- 12202113
TI  - Third position codon composition suggests two classes of genes within the
      Cauliflower mosaic virus genome.
AB  - The translation of viral mRNAs by host ribosomes is essential for infection.
      Hence, codon usage of virus genes may influence efficiency of infection. In
      addition, composition of nucleotides in the third position within codons of genes
      can reflect evolutionary relationships. In this study, third position codon
      composition was examined for the seven genes of eight Cauliflower mosaic virus
      isolates. Genes IV-VII had similar codon composition values and were termed Class
      1 genes. Genes I-III possessed corresponding codon composition values and were
      termed Class 2 genes. The codon composition values of Class 1 and genes differed
      significantly. Neither Class 1 nor Class 2 genes had codon composition values
      identical to that of the host plant, Arabidopsis thaliana. However, Class 1 genes
      possessed codon composition values closer to those of the host than Class 2
      genes. Examination of the genomes of three Rous sarcoma virus isolates indicated
      that codon composition values were similar for the gag, pol, and env genes but
      these genes differed significantly from the src genes. Since codon composition
      values for Rous sarcoma virus distinguished a "foreign" gene from the rest of the
      viral genome, it is possible that the Cauliflower mosaic virus genome is composed
      of genes from two different sources. Others have suggested that Cauliflower
      mosaic virus evolved in this manner and our data provide support for this
      hypothesis.

PMID- 12202114
TI  - A frequency distribution for the number of hematogenous organ metastases.
AB  - The number of metastases associated with a primary tumor can be a major
      determinant for the chance of cure. A model is proposed here where the frequency
      distribution of the number of experimental organ metastases is affected by
      Poisson statistics, and by stochastic variations in regional blood flow. The
      model predicts that the mean E (X) and variance var (X) of the number of
      metastases per organ should relate according to a power function,var (X)= E
      (X)(p)+E (X), where and p are the constants, and that the actual distribution has
      a Poisson-negative binomial form. This model was found consistent with the data
      derived from a meta-analysis of over 47 000 murine experimental metastases. This
      frequency distribution (together with knowledge of the size distribution for
      metastases and the fraction of clonogenic cells) could permit more accurate
      assessments for tumor control probabilities with adjuvant therapies.

PMID- 12202115
TI  - Evolution of mutualism between globeflowers and their pollinating flies.
AB  - Plant/seed-eater pollinators mutualisms involve a plant pollinated by an insect
      whose larvae develop by eating a fraction of host-plant seeds. The outcome of the
      interaction therefore depends on the number of ovules fertilized by adult visits
      and the number of seeds destroyed by larvae. Among the very few cases of such
      mutualisms reported so far is the globeflower-globeflower flies mutualism, which
      is unique in that it involves several congeneric fly species (Chiastocheta genus)
      coexisting within a single host-plant species, Trollius europaeus. These species
      exhibit contrasted oviposition behaviors resulting in a more or less beneficial
      outcome for the plant. We designed an adaptive dynamics model to investigate how
      morphological traits of globeflower could affect the evolution of oviposition in
      its pollinating flies. Three fly traits (flower age at oviposition, clutch size
      and the level of avoidance of already parasitized flowers) and one plant trait
      (closed or open corolla) were examined. Whatever the shape of the flower,
      evolutionary branching occurs between early and late ovipositing flies, driven by
      strong competition among larvae within a fruit. Once this branching occurred, the
      closed shape of the corolla is likely to offer a better protection to eggs of
      early but not of late ovipositing flies. The difference in egg survival results
      in higher competition among early larvae and thus selects for decreased clutch
      size in early flies. This can be seen as a first step in the evolution of a
      mutualistic behavior. The prediction of our model fits field observations of fly
      behavior, giving theoretical support to the hypothesis of fly sympatric
      speciation within its host plant. Moreover, flower closed globe shape can be
      positively selected in globeflowers as it results in a reduction of parasitism
      strength. This last evolution therefore leads to a stable mutualism between
      globeflowers and globeflower flies.

PMID- 12202116
TI  - Co-evolution of the genetic code and ribozyme replication.
AB  - The origin of translation has stimulated much discussion since the basic
      processes involved were deciphered during the 1960s and 1970s. One strand of
      thought suggested that the process originated from RNA replication in the RNA
      world (Weiner & Maizels, 1987, 1994). In this paper I seek to extend this model.
      The mRNA originates as a replication intermediate of minus-strand ribozyme
      replication and thus contains all the genetic information contained in both the
      ribozyme portion and the putative tRNA-like portion of the RNA molecule.
      Qualitatively, this is similar to the model for the origin of chromosomes
      (Szathmary & Maynard-Smith, 1993, Maynard-Smith & Szathmary, 1993). This model
      explicitly describes the evolution of early chromosomes and the role replication
      played in generating the modern mRNA. Moreover, by pursuing this model, the START
      and STOP codons were derived and their original function with regard to the
      primitive 23S ribosomal RNA is suggested. Co-evolution of the genetic code (Wong,
      1975) is also contained within the model. Lastly, I address some of the benefits
      and costs that the process may have for the organism in the context of autotrophy
      in the RNA world.

PMID- 12202117
TI  - Random walk models of worker sorting in ant colonies.
AB  - Sorting can be an important mechanism for the transfer of information from one
      level of biological organization to another. Here we study the algorithm
      underlying worker sorting in Leptothorax ant colonies. Worker sorting is related
      to task allocation and therefore to the adaptive advantages associated with an
      efficient system for the division of labour in ant colonies. We considered four
      spatially explicit individual-based models founded on two-dimensional correlated
      random walk. Our aim was to establish whether sorting at the level of the worker
      population could occur with minimal assumptions about the behavioural algorithm
      of individual workers. The behaviour of an individual worker in the models could
      be summarized by the rule "move if you can, turn always". We assume that the
      turning angle of a worker is individually specific and negatively dependent on
      the magnitude of an internal parameter micro which could be regarded as a measure
      of individual experience or task specialization. All four models attained a level
      of worker sortedness that was compatible with results from experiments
      onLeptothorax ant colonies. We found that the presence of a sorting pivot, such
      as the nest wall or an attraction force towards the centre of the worker
      population, was crucial for sorting. We make a distinction between such pivots
      and templates and discuss the biological implications of their difference.

PMID- 12202118
TI  - Complementary/alternative medicine in rheumatology--between negligence, ignorance
      and arrogance.

PMID- 12202119
TI  - Effects of agonists of peroxisome proliferator-activated receptor gamma on
      proteoglycan degradation and matrix metalloproteinase production in rat cartilage
      in vitro.
AB  - OBJECTIVE: To examine the effects of agonists of peroxisome proliferator
      activated receptor (PPAR) gamma on proteoglycan degradation induced by
      interleukin (IL)-1beta or tumor necrosis factor (TNF)alpha in cartilage in vitro.
      DESIGN: Proteoglycan degradation was measured as release of radioactivity from
      rat cartilage explants previously labeled with (35)SO2-4. Western blots were used
      to examine tissue levels of aggrecan neoepitopes NITEGE and VDIPEN, generated by
      aggrecanases and matrix metalloproteinases (MMP), respectively. Production of MMP
      2, -3 and -9 by cultured rat chondrocytes was measured by zymography and by
      fluorimetric assay. RESULTS: IL-1beta-induced proteoglycan degradation was likely
      due to aggrecanase, since it was associated with a strong increase of NITEGE
      signal. MMP-dependent VDIPEN signal increased only after further incubation with
      pro-MMP activator APMA. PPAR agonists 15d-PGJ(2) and GI262570 (10 microM)
      inhibited IL-1beta- and TNFalpha-induced proteoglycan degradation measured both
      before and after addition of APMA. The agonists also inhibited cytokine-induced
      MMP production by isolated chondrocytes. CONCLUSION: This study shows that
      PPARgamma agonists inhibit cytokine-induced proteoglycan degradation mediated by
      both aggrecanase and MMP. This effect is associated with inhibition of production
      of MMP-3 and -9. These results support the interest for PPARgamma agonists as
      candidate inhibitors of pathological cartilage degradation.

PMID- 12202120
TI  - Efficacy of intraarticular hyaluronic acid in patients with osteoarthritis--a
      prospective clinical trial.
AB  - AIM: The goal of this study was to determine whether or not the intraarticular
      administration of hyaluronic acid can improve functional parameters, such as
      isokinetic muscle strength or total work and clinical test results in patients
      with osteoarthritis (OA) of the knee. METHOD: As part of a prospective,
      controlled study 43 patients with osteoarthritic changes of both knees
      (radiographic Kellgren stage II-III) were followed in a right/left comparison.
      The influence of intraarticularly injected hyaluronic acid (20mg hyaluronic
      acid/2ml Hyalart) on functional and clinical parameters was analysed. We used the
      isokinetic system Cybex 600 for measuring maximal isokinetic muscle strength and
      total work. A total of 20 males and 23 females fulfilled the inclusion criteria
      with an age between 55-78 years and underwent five injections of hyaluronic acid
      (one injection per week). The injected knee represented the treatment group,
      while the contralateral knee served as the control. RESULTS: The maximum peak
      torque of the knee extensors in the treatment group was measured between 57+/
      26.15/32.33+/-19.63Nm prior to the injections and 77.17+/-32.54/47.83+/-21.43Nm
      following the hyaluronic acid therapy (P< 0.01). The analysis of the knee flexors
      at angular velocities of 60 degrees /s and 180 degrees /s revealed values of
      40.44+/-21.58/22.89+/-16.64Nm and 53.55+/-24.26/34.05+/-17.37Nm (P< 0.01)
      respectively. The evaluation of the total work of the knee flexors and extensors
      revealed a significant difference (P< 0.01) between the treatment and control
      group. The Lequesne score was reduced from 13.57+/-1.88 prior to the injections
      to 7.94+/-2.53 after the treatment (P< 0.01). The pain score was documented with
      the help of a visual analog scale. The VAS values were reduced at rest from
      3.83+/-1.72cm to 1.36+/-1.42cm and during weight bearing from 7.57+/-1.34cm to
      3.75+/-1.32cm in the treatment group (P< 0.01). CONCLUSIONS: This controlled
      prospective clinical trial confirmed that 5 weekly intraarticular injections of
      HA (Hyalart) in patients with OA of the knee provide pain relief and functional
      improvements.

PMID- 12202121
TI  - Serum cartilage oligomeric matrix protein and clinical signs and symptoms of
      potential pre-radiographic hip and knee pathology.
AB  - OBJECTIVE: To examine the cross-sectional relationship between serum cartilage
      oligomeric matrix protein (COMP) and hip and knee clinical signs and symptoms in
      a sample of adults without radiographic hip or knee osteoarthritis (OA). DESIGN:
      A total of 145 persons with available sera and no evidence of radiographic hip or
      knee OA (Kellgren-Lawrence grade 0) were randomly selected from the Caucasian
      participants of the Johnston County Osteoarthritis Project. COMP was quantified
      by a competitive ELISA assay with a monoclonal antibody 17-C10. Hip and knee
      clinical signs and symptoms were assessed by physical examination and interview,
      and their associations with Ln COMP analysed with general linear models. RESULTS:
      After adjustment for age, gender, body mass index (BMI), and other symptomatic
      joints, mean Ln COMP was statistically significantly higher among persons with
      hip-related clinical signs (P=0.018), among those with hip-related symptoms
      (P=0.046), and among individuals meeting American College of Rheumatology
      clinical criteria for hip OA (P=0.021). There were no statistically significant
      associations between any of the knee-related clinical signs and symptoms and Ln
      COMP. CONCLUSION: Serum COMP may be useful as a biomarker of pre-radiographic hip
      joint pathology; its utility as a biomarker of pre-radiographic knee joint
      pathology is unclear.

PMID- 12202122
TI  - A slow release formulation of insulin as a treatment for osteoarthritis.
AB  - OBJECTIVE: To examine the potential of insulin, in a sustained delivery system,
      as a treatment for arthritis. DESIGN: The effect of insulin on matrix synthesis,
      matrix breakdown, and nitric oxide production in primary cartilage explants was
      examined. The activity of insulin on diseased cartilage from Dunkin Hartley
      guinea pigs, diabetic mice, and osteoarthritic patients was measured. The
      specificity of insulin stimulation was compared to that of IGF-I using
      osteoblasts and fibroblasts. Finally, the stability of insulin in a biologically
      relevant system was tested, and a slow-release formulation of insulin was
      developed and characterized. RESULTS: In articular cartilage explants, insulin
      stimulated proteoglycan (PG) synthesis, inhibited PG release and nitric oxide
      production, and overcame the detrimental effects of interleukin 1 (IL-1). The
      mechanism whereby insulin decreased matrix breakdown was through inhibition of
      aggrecanase activity. Insulin was active on cartilage at concentrations at which
      insulin does not cross-react with insulin-like growth factor I (IGF-I) receptors
      nor stimulate proliferation of other cells types. The response of cartilage to
      insulin did not diminish with age or disease. Insulin stimulated matrix synthesis
      in osteoarthritic cartilage and local treatment with insulin overcame endogenous
      suppression of matrix synthesis in diabetic cartilage. Poly-lactic-coglycolic
      acid (PLGA) was found to be an effective carrier for delivery of insulin, and
      PLGA-Insulin was active on articular cartilage in vitro and in vivo. CONCLUSIONS:
      As the incidence of arthritis increases with the aging population, an effective
      therapy to induce repair of cartilage is needed. Based on its biological
      activities, insulin appears to be an attractive protein therapeutic candidate.
      Maximum insulin effectiveness may require a sustained delivery system.

PMID- 12202123
TI  - Serum levels of cartilage oligomeric matrix protein (COMP) correlate with
      radiographic progression of knee osteoarthritis.
AB  - OBJECTIVE: To evaluate the prognostic utility of serum COMP level measured with a
      new sandwich ELISA, by correlating COMP level with outcome measures of
      osteoarthritis (OA) progression. DESIGN: Patients (N=48) had symptomatic primary
      knee OA of Kellgren-Lawrence (K-L) grade I-III and met ACR criteria. These
      patients were evaluated prospectively as part of a double-blind drug trial of 3
      years' duration and represented the placebo arm of the study. Serum COMP levels
      were measured by sandwich ELISA with monoclonal antibodies 16-F12 and 17-C10 at
      baseline and at study end and levels were correlated with changes in (1) joint
      space width (JSW), (2) K-L grade, (3) Lequesne, and (4) WOMAC indices, over 3
      years. RESULTS: The change in JSW over 3 years, summed for both knees, correlated
      positively with serum COMP level at baseline as well as at study end. Patients
      were sorted by level of progression based upon a change in K-L grade summed for
      both knees over 3 years; patients who progressed by two K-L grades were shown to
      have had significantly higher COMP levels at baseline as well as at study end.
      Baseline and study end COMP levels did not correlate with the change of Lequesne
      or WOMAC indices. Baseline COMP levels correlated strongly with end serum COMP
      levels. CONCLUSION: Serum COMP has the potential to be a prognostic marker of
      disease progression. High COMP levels, persisting over the 3-year study period in
      the patients with radiographic progression, indicated differences in disease
      activity detectable throughout the entire follow-up interval.

PMID- 12202124
TI  - Biomarkers of joint tissue metabolism in canine osteoarthritic and arthritic
      joint disorders.
AB  - OBJECTIVE: To explore the levels of matrix metalloprotease-3 (MMP-3), tissue
      inhibitor of metalloproteases-1 (TIMP-1), 5D4 keratan sulfate, and two 3B3
      chondroitin-sulfate epitopes in several canine osteoarthritic and inflammatory
      arthropathies. METHODS: Blood and synovial fluid were obtained from 103 dogs with
      rupture of the anterior cruciate ligament (ACLR), osteochondritis dissecans
      (OCD), fragmented coronoid process (FPC), patella luxation (PL), hip dysplasia
      (HD) or infectious arthritis. Dogs with non-musculosceletal disorders were used
      as controls. The biomarkers were measured by immunoassays. RESULTS: Median levels
      of synovial MMP-3, TIMP-1 and molar ratios of MMP/TIMP-1 were significantly
      higher in the arthritis than in the control group. The release of 5D4 keratan
      sulfate epitope and serum 3B3 neoepitope was reduced in arthritis patients.
      Increases in synovial TIMP-1 in OA were less pronounced and the molar ratio of
      MMP-3/TIMP-1 remained far below 1.0, demonstrating a surplus of the protease
      inhibitor. In osteoarthritic patients median levels of synovial 5D4 keratan
      sulfate were up-regulated after ACLR and PL and were inversely correlated with
      increasing duration of lameness. Serum TIMP-1 levels were significantly reduced
      in the joint disorder group when compared with the control group. CONCLUSION: Our
      observations present the TIMP-1 serum level as a potential marker for the
      detection of degenerative changes in cartilage and also indicate that in canine
      OA, the MMP-3 mediated matrix destruction is not of major importance. However MMP
      3 seems to be a sensitive marker for the local inflammation in canine arthritis.

PMID- 12202125
TI  - Metalloproteinase and tissue inhibitor of metalloproteinase expression in the
      murine STR/ort model of osteoarthritis.
AB  - OBJECTIVE: To study the temporal expression of matrix metalloproteinases and
      tissue inhibitors of metalloproteinases in the STR/ort mouse model of
      osteoarthritis, using in situ hybridization with oligonucleotide probes and
      specific antisera for each protein. METHODS: In situ hybridization and
      immunolocalization experiments were performed on serial cryosections of knee
      joints from STR/ort and control CBA mice. The mRNA was localized using
      digoxygenin-labeled probes. RESULTS: MMP2, MMP3, MMP7, MMP9, MMP13, MT1-MMP and
      TIMP2 mRNA was detected in the tibial articular chondrocytes of STR/ort mice at
      all ages (12, 18, 24, 30 and 35 weeks). Levels were always higher than in age
      matched CBA mice. Neither MMP8 nor TIMP1 mRNA was detected in murine cartilage.
      The location and distribution of each of the MMP mRNA transcripts varied within
      the tibial plateau. Immunolocalization consistently detected MMP3 and MT1-MMP in
      articular cartilage and MMP13 in calcified cartilage. Other proteases and their
      inhibitors were not detected in either of these cartilages but MMP2 and MMP9 were
      immunolocalized in bone marrow cells and growth cartilage respectively.
      CONCLUSION: Expression of all the detected MMPs and TIMP-2 is up-regulated in
      STR/ort mice at the mRNA level. However, failure to detect protein expression for
      MMPs 2, 7, 9, 13 and TIMPs 1 and 2 in murine chondrocytes by immunohistochemistry
      indicates that the changes in mRNA levels in STR/ort mice must be interpreted
      with caution.

PMID- 12202126
TI  - Fibronectin fragments upregulate insulin-like growth factor binding proteins in
      chondrocytes.
AB  - Addition of fibronectin fragments (Fn-fs) to cultured cartilage explants has been
      shown to mediate extensive cartilage matrix degradation followed by anabolic
      responses. OBJECTIVE: To determine whether specific Fn-fs regulate cartilage
      metabolism through a mechanism, in part, involving insulin-like growth factor
      (IGF) and insulin-like growth factor binding proteins (IGFBPs). METHODS: Primary
      bovine articular chondrocyte cultures were treated with Fn-fs. mRNA from the
      cultures was analysed by Northern blotting. Changes in the levels of IGFBPs in
      cellular extracts and conditioned media were analysed by Western ligand blotting.
      Explant cultures of bovine articular cartilage were used to assay release of
      exogenous IGF-I and IGFBP-2. An analog of IGF-I with altered affinity for IGFBPs
      was used to assay the effect of IGFBPs on proteoglycan synthesis. RESULTS: The Fn
      fs increased protein levels of IGFBPs-2, -3 and -5 in conditioned media and of
      IGFBP-2 in cell extracts by as much as nine-fold. Conversely, the protein level
      of constitutively expressed IGBP-4 was decreased in conditioned medium. Northern
      blot analysis reflected increased IGFBP-3 mRNA but not decreased IGFBP-4 mRNA.
      The IGF-I analog was more effective at restoring PG synthesis suppression by Fn
      fs than was wild type IGF-I. CONCLUSIONS: The Fn-fs increased levels of IGFBPs in
      cultures of bovine articular chondrocytes and elicited release of IGFBP-2 and IGF
      I from articular cartilage. The increased level of IGFBPs may trap IGF-I and
      account in part for the initial suppression of PG synthesis. Induced proteinases
      may subsequently liberate IGF-I and cause greatly enhanced anabolic processes,
      contributing to cartilage repair.

PMID- 12202128
TI  - Achievable accuracy of parameter estimation for multidimensional NMR experiments.
AB  - A fundamental issue in NMR spectroscopy is the estimation of parameters such as
      the Larmor frequencies of nuclei, J coupling constants, and relaxation rates. The
      Cramer-Rao lower bound provides a method to assess the best achievable accuracy
      of parameter estimates resulting from an unbiased estimation procedure. We show
      how the Cramer-Rao lower bound can be calculated for data obtained from
      multidimensional NMR experiments. The Cramer-Rao lower bound is compared to the
      variance of parameter estimates for simulated data using a least-squares
      estimation procedure. It is also shown how our results on the Cramer-Rao lower
      bound can be used to analyze whether an experimental design can be improved to
      provide experimental data which can result in parameter estimates with higher
      accuracy. The concept of nonuniform averaging in the indirect dimension is
      introduced and studied in connection with nonuniform sampling of the data.

PMID- 12202127
TI  - Chondrocyte apoptosis following intraarticular fracture in humans.
AB  - OBJECTIVE: The primary objective of the present study was to establish the degree
      to which chondrocyte apoptosis occurs in vivo following intraarticular fractures
      in humans. DESIGN: Fracture cartilage specimens were obtained from patients
      undergoing surgical intervention for fractures of the articular surface of the
      proximal tibia. Normal proximal tibia cartilage specimens served as controls.
      Apoptotic chondrocytes were identified and quantified using TUNEL analysis.
      RESULTS: The percentage of TUNEL positive chondrocytes in the fractured articular
      cartilage specimens (mean 18.5%, range 1-44%) was found to be an order of
      magnitude higher than the percentage observed in control specimens (mean 1.9%,
      range 0-4%). CONCLUSIONS: The percentage of TUNEL positive chondrocytes following
      intraarticular fracture is much higher than that reported for chronic
      degenerative conditions such as osteoarthritis and rheumatoid arthritis. These
      data provide strong evidence that chondrocyte apoptosis is a consequence of
      intraarticular fracture and suggest that chondrocyte apoptosis may play a
      particularly significant role in the subsequent development of post-traumatic
      arthritis.

PMID- 12202129
TI  - The application of MAS recoupling methods in the intermediate motional regime.
AB  - We present investigations concerning the effect of molecular motions on the
      experimental timescale upon the recoupling of anisotropic interactions under
      magic-angle spinning conditions. An approach for the efficient simulation of spin
      dynamics occurring during complex pulse sequences, based on a linearization of
      the general solution of the stochastic Liouville-von Neumann equation, was
      developed. Using (13)C CSA recoupling of the methyl carbon in dimethylsulfon as a
      sample interaction, we observed a characteristic signal decay under recoupling
      upon entering the intermediate motional regime, which can be well described by an
      apparent transverse relaxation time, T(2)(rcpl). This quantity does not depend on
      the spinning frequency to a first approximation. Specific recoupling experiments,
      namely the measurement of tensor parameters by spinning sideband analysis, and
      the determination of rate constants with the CODEX experiment, are discussed with
      respect to possibilities and limits of their application in the intermediate
      motional regime. Important conclusions are drawn with regards to the limited
      applicability of popular recoupling methods like REDOR to samples exhibiting
      intermediate mobility.

PMID- 12202130
TI  - Quantitative measurement of two-dimensional distribution functions of diffusion
      and relaxation in grossly inhomogeneous fields.
AB  - We demonstrate the quantitative extraction of multidimensional distribution
      functions in the presence of grossly inhomogeneous fields. Examples are shown for
      diffusion-T(2) distribution functions and T(1)-T(2) distribution functions. The
      pulse sequences consist of an initial editing sequence followed by a long series
      of nominal 180 degrees pulses. They are designed such that the kernels describing
      the relationships between the distribution functions and the measured data are
      separable. The required phase cycling is discussed. We analyze in detail the
      extra spin dynamics effects due to the strong field inhomogeneities including the
      effects on diffusion and relaxation. A recently developed algorithm is used to
      invert the data and extract stable multidimensional distribution functions in an
      efficient manner. We present examples for several applications of this new
      technique. Diffusion-relaxation distribution functions can be used for fluid
      identification and for the characterization of pore geometry of porous media
      based on the effects of restricted diffusion. We have also determined T(1)-T(2)
      distribution functions of water saturated sedimentary rock and find excellent
      agreement with previous measurements performed in homogeneous fields.

PMID- 12202131
TI  - Proton dipolar recoupling in resin-bound peptides under high-resolution magic
      angle spinning.
AB  - Rotational resonance and radiofrequency-driven dipolar recoupling (RFDR)
      experiments have been used to recover the weak proton dipolar interaction present
      in peptides bound to swollen resins spun at the magic angle. The intensity of the
      correlation peaks obtained using these sequences is shown to be significantly
      stronger than the one obtained using the classical NOESY experiment. In addition,
      it is found that during the relatively long mixing times required to transfer
      magnetization in such soft materials, the RFDR sequence also achieves
      magnetization transfer via the scalar J-coupling.

PMID- 12202132
TI  - Quantifying the lateral lipid domain properties in erythrocyte ghost membranes
      using EPR-spectra decomposition.
AB  - Using EPR spectroscopy a typical lateral domain structure was detected in the
      membranes of spin-labeled bovine erythrocyte ghosts. The spectral parameters were
      determined by decomposing the EPR spectrum into three spectral components and
      tuned by a hybrid-evolutionary-optimization method. In our experiments the
      lateral domain structure and its properties were influenced by the variation in
      the temperature and by the addition of n-butanol. The specific responses of the
      particular domain types were detected. For the most-ordered domain type a break
      was seen in the temperature dependence of its order parameter, while the order
      parameters of the two less-ordered domain types exhibited a continuous decrease.
      Below the break-point temperature the alcohol-induced membrane fluidity variation
      is mainly a consequence of the change in the proportions of the least- and the
      most-ordered domain type and not the change of the domain-type ordering or
      dynamics (with n-butanol concentration). On the other hand, the fluidity
      variation above the break-point temperature arises from both types of changes.
      Interestingly, the proportion of the domain type that has its order parameter
      between that of the least- and the most-ordered domain type remains almost
      constant with concentration as well as with temperature, which implies its
      stability. Such characterization of the lateral membrane domain structure could
      be beneficial when considering the lipid-protein interactions, because it can be
      assumed that the activity of the membrane-bound enzyme depends on the properties
      of the particular domain type.

PMID- 12202133
TI  - Electron dipole-dipole ESEEM in field-step ELDOR of nitroxide biradicals.
AB  - The use of a rapid stepping of the magnetic field for investigation of electron
      dipole-dipole ESEEM in pulsed X-band ELDOR is described. The magnetic field jump,
      synchronized with a microwave pumping pulse, is positioned between the second and
      the third pulses of the stimulated echo pulse sequence. This echo is measured as
      a function of the delay between the first and the second pulses. The data are
      analyzed for a Fourier transform resulting in a Pake resonance pattern. To remove
      the electron-nuclear contributions to ESEEM, time traces with pumping were
      divided by those without. This resulted in complete elimination of electron
      nuclear contributions, which is seen from the absence of peaks at nuclear
      frequencies and the similarity of results for protonated and deuterated solvents.
      For increasing the electron-electron modulation depth, a scanning of the magnetic
      field during the microwave pumping is proposed. The interspin distances and their
      distribution are determined for two long-chained (ca. 2 nm) nitroxide biradicals
      in glassy toluene and in frozen nematic liquid crystal 4-cyano-4'-pentyl
      biphenyl. For the latter solvent, the alignment of the axis connecting two
      nitroxides in biradicals is quantitatively analyzed.

PMID- 12202134
TI  - Combined k-space q-space pulsed ESR imaging: mapping of restricted diffusion in
      (FA)(2)PF(6).
AB  - A (FA)(2)PF(6) crystal from the family of the quasi-one-dimensional organic
      conductors was selectively damaged by a beam of Helium ions with a slitted mask
      placed in the beam's trajectory. Pulsed ESR density weighted imaging of the
      damaged crystal revealed the appearance of regions where the ESR signal was
      absent. The one-dimensional motion of the charge carriers was thus restricted to
      the undamaged sections. The local charge carrier spin dynamics in these
      restricted areas was probed by combined k-space q-space pulsed ESR imaging. The
      local expected appearance of the restricted pulsed gradient spin echo (PGSE)
      "diffusive diffraction" effect is shown. The position of the diffraction minima
      is compatible with the density imaging results.

PMID- 12202135
TI  - Complex response function of magnetic resonance spectrometers.
AB  - A vectorial analysis of magnetic resonance spectrometers, based on traveling wave
      resonators and including the reference arm and the automatic control of
      frequency, has been developed. The proposed model, valid also for stationary wave
      resonators, gives the response function of the spectrometer for any working
      condition, including scalar detectors with arbitrary response law and arbitrary
      excitation frequency. The purely dispersive and purely absorptive linear
      responses are discussed in detail for different scalar detectors. The developed
      approach allows for optimizing the performances of the spectrometer and for
      obtaining the intrinsic lineshape of the sample in a very broad range of working
      conditions. More complex setups can be modeled following the proposed scheme.

PMID- 12202136
TI  - Categories of coherence pathways for the CPMG sequence.
AB  - The CPMG sequence has been extremely useful for efficient measurements of NMR
      signal, spin-spin relaxation, and diffusion, particularly in inhomogeneous
      magnetic fields, such as when samples are outside the magnet and RF coil. Due to
      the inaccuracy of the pulses and the off-resonance effects, the CPMG echoes have
      contributions from the Hahn echo as well as signals that are similar to
      stimulated echoes. The systematic understanding of the CPMG pulse sequence
      requires decomposing the magnetization dynamics into different coherence
      pathways. In this paper, we describe a method to classify the CPMG coherence
      pathways and illustrate the nature of these types of pathways. This
      classification shows that direct echo and stimulated echoes are the major
      contribution to the CPMG signal. It also provides a clear understanding of the
      effect of restricted diffusion in porous media.

PMID- 12202137
TI  - Effects of restricted diffusion on MR signal formation.
AB  - Numerous functional MRI (fMRI) and diffusion MR studies have recently boosted
      interest in the theory of MR signal formation in biological systems in the
      presence of mesoscopic magnetic field in homogeneities. Herein we report an exact
      solution to the problem of free induction decay (FID) and spin echo (SE) signal
      formation in the presence of a constant field gradient in three models of one-,
      two-, and three-dimensional restricted diffusion. We demonstrate the transition
      with increasing diffusion coefficient from the oscillating FID signal behavior in
      the static dephasing regime to a monotonic exponential behavior in the motional
      narrowing regime. Quantitative criteria are presented for applicability of the
      Gaussian approximation for the description of the MR signal. The spatial
      distribution of signal density and the edge enhancement effect are analyzed. We
      also demonstrate that the presence of restrictive barriers in a one-compartment
      model can lead to a quasi-two-compartment behavior of the MR signal. This result
      suggests a simple rationale for the experimental findings of biexponential echo
      attenuation curves in MR diffusion experiments with tissue systems.

PMID- 12202138
TI  - Multiple quantum dynamics in linear chains and rings of nuclear spins in solids
      at low temperatures.
AB  - Multiple quantum spin dynamics is studied using analytical and numerical methods
      for one-dimensional finite systems of nuclear spins 12 coupled by dipole-dipole
      interactions at low temperatures. Exact expressions for intensities of multiple
      quantum coherences at low temperatures were obtained in the approximation of the
      nearest neighbor interactions. The time growth of multiple quantum coherences was
      analyzed numerically when all the dipole-dipole interactions in one-dimensional
      systems consisting of 6/8 spins were taken into account. It is shown that the
      growth of multiple quantum coherences gets faster when the temperature decreases,
      and the intensities of multiple quantum coherences can be negative at low
      temperatures.

PMID- 12202139
TI  - Polarity contributions to hyperfine splittings of hydrogen-bonded nitroxides--the
      microenvironment of spin labels.
AB  - A self-consistent treatment of reaction field effects on isotropic (14)N
      hyperfine coupling constants of nitroxide spin labels in mixtures of polar and
      apolar solvents is given based on the Onsager approach. It is shown that this
      works reasonably well for mixtures of water or methanol with dioxane, far better
      than do conventional approaches using the Clausius-Mossotti relation. Association
      constants, K(A,h), for hydrogen bonding of protic solvents to nitroxides are
      derived in this way from published EPR data. A value of K(A,h) approximately 1.0
      M x (-1) is argued to be reasonable for water in a hydrophobic environment. Data
      from spin-labelled lipids can then be used to estimate effective water
      concentrations in biological membranes.

PMID- 12202140
TI  - Assignment strategy for proteins with known structure.
AB  - In protein NMR the assignment of nuclear spin resonances is a prerequisite for
      all subsequent applications, such as studies of ligand binding, protein-DNA
      interactions, and dynamics. Resonance assignment is a time consuming step even
      when the 3D x-ray structure of the protein is available. A new strategy is
      presented to solve the "inverse" assignment problem, which is the determination
      of the NMR resonance assignment from a known 3D protein structure. The protocol
      employs NMR data in the form of residual dipolar couplings and chemical shifts,
      while it does not require any sequential NMR connectivity information. The
      assignment problem is mathematically formulated in terms of a weighted matching
      problem that can be computationally efficiently solved by a combinatorial
      optimization algorithm. The protocol is applied to ubiquitin using two or three
      residual dipolar couplings per amino acid measured in Pfl phage medium together
      with chemical shift information. The algorithm yields for more than 90% of the
      protein backbone resonances the correct assignment.

PMID- 12202141
TI  - High-resolution DOSY NMR with spins in different chemical surroundings: influence
      of particle exchange.
AB  - The effect of chemical exchange in the diffusion-ordered (DOSY) spectra of a two
      site system in the slow-exchange limit with respect to the chemical shift is
      studied. The problem is addressed both theoretically and experimentally. The
      relationship between diffusion time (t) and mean lifetimes (tau) is studied by
      the simulation of the magnetization attenuations as a function of the gradient
      strength, under PFG conditions. The influence of the difference in populations
      and diffusion coefficients of the two sites is also considered. In analogy to the
      limiting cases of fast- and slow-exchange with respect to the chemical shift,
      limiting cases with respect to the diffusion dimension are defined. The slow
      exchange limit in diffusion corresponds to the relation of t and tau that allows
      us to observe the two spins in exchange associated with the individual diffusion
      coefficients of the two sites when no exchange is present. The fast-exchange
      limit in diffusion is reached when the relation of t and tau is such that the two
      spins present the same apparent diffusion coefficient. By using a model system
      consisting of water/t-butanol it is shown that by recording several DOSY
      experiments with increasing diffusion times it is possible to estimate the value
      of the exchange rate.

PMID- 12202142
TI  - Cesium adsorption in hydrated iron oxide particles suspensions: an NMR study.
AB  - 137Cs is an important component of nuclear waste which may pollute water. Its
      migration in natural environments is slowed down by adsorption on minerals.
      Cesium adsorption on akaganeite (beta-FeOOH) particles, dextran-coated
      ferrihydrite (5 Fe(2)O(3)-9H(2)O) particles, and ferritin in aqueous solutions is
      studied with (133)Cs nuclear magnetic resonance measurements. The longitudinal
      relaxation time (T(1)) of (133)Cs in the presence of such magnetic particles
      depends on whether the ions bind to the particle or not. T(1) of (133)Cs ions in
      aqueous solutions containing the same amount of magnetized particles will not
      depend on cesium concentration if relaxation is governed by diffusion (when
      cesium is not able to bind), but it will depend on cesium concentration if
      exchange governs relaxation (when cesium is able to bind). The method is
      successfully tested using TEMPO, a nitroxide stable free radical whose relaxation
      is due to diffusion. (133)Cs relaxation in solutions of ferritin, akaganeite, and
      dextran-coated ferrihydrite particles is found to result from a cationic exchange
      of cesium ions between particles surface and bulk ions, owing to adsorption. The
      effect of pH on (133)Cs relaxation in solutions of the particles is consistent
      with the adsorption properties of cations on hydrated iron oxides.

PMID- 12202143
TI  - Cross-polarization from the dipolar reservoir under the mismatched Hartmann-Hahn
      condition.
AB  - Cross-polarization from the dipolar reservoir for a range of mismatched Hartmann
      Hahn conditions has been considered. Experiment, in general, agrees with the
      dispersive Lorentzian behavior expected on the basis of quasi-equilibrium theory.
      It is observed that inclusion of additional mechanisms of polarization transfer
      lead to an improvement of the fit of the experimental results. The utility of
      extending the technique to the case of ordered long chain molecules, such as
      liquid crystals, for the measurement of the local dipolar field is also
      presented.

PMID- 12202144
TI  - Towards rapid and unique curve resolution of low-field NMR relaxation data:
      trilinear SLICING versus two-dimensional curve fitting.
AB  - In this work an alternative method, named SLICING, for two-dimensional and
      noniterative T(2) decomposition of low-field pulsed NMR data (LF-NMR) is proposed
      and examined. The method is based on the Direct Exponential Curve Resolution
      Algorithm (DECRA) proposed by W. Windig and A. Antalek (1997, Chemom. Intell.
      Lab. Syst.37, 241-254) and takes advantage of the fact that exponential decay
      functions, when translated in time, retain their characteristic relaxation times
      while only their relative amounts or concentrations change. By such simple
      translations (slicing) it is possible to create a new "pseudo" direction in the
      relaxation data and thus facilitate application of trilinear (multiway) data
      analytical methods. For the application on LF-NMR relaxation data, the method has
      two basic requirements in practice: (1) two or more samples must be analyzed
      simultaneously and (2) all samples must contain the same qualities (i.e.,
      identical sets of distinct T(2) values). In return, if these requirements are
      fulfilled, the SLICING (trilinear decomposition) method provides very fast and
      unique curve-resolution of multiexponential LF-NMR relaxation curves and, as a
      spin-off, calibrations to reference data referring to individual proton
      components require only scaling of the resulting unique concentrations. In this
      work the performance of the SLICING method (including multiple slicing schemes)
      is compared to a traditional two-dimensional curve fitting algorithm named
      MATRIXFIT through application to simulated data in a large-scale exhaustive
      experimental design and the results validated by application to two small real
      data sets. Finally a new algorithm, Principal Phase Correction (PPC) based on
      principal component analysis, is proposed for phase rotation of CPMG quadrature
      data, an important prerequisite to optimal SLICING analysis.

PMID- 12202145
TI  - Anisotropic water diffusion in macroscopically oriented lipid bilayers studied by
      pulsed magnetic field gradient NMR.
AB  - The anisotropy, D(parallel)/D( perpendicular ), of water diffusion in fully
      hydrated bilayers of dimyristoylphosphatidylcholine at 29 degrees C has been
      measured by pulsed magnetic field gradient (pfg) NMR. By using NMR imaging
      hardware to produce magnetic field gradients in an arbitrary direction with
      respect to a stack of macroscopically aligned lipid bilayers, translational
      diffusion of water was measured as a function of the angle between the direction
      of the magnetic field gradient and the normal of the lipid membrane. The observed
      diffusion coefficient is found to depend strongly on this angle. The anisotropy
      cannot be accurately determined due to the very small value of D( perpendicular
      ), but a lower limit of about 70 can be estimated from the observed diffusion
      coefficients. The results are discussed in terms of the relatively low
      permeability of water across the lipid bilayer, instrumental limitations, and/or
      possible defects in the lamellae.

PMID- 12202146
TI  - Sensitivity enhancement in multiple-quantum NMR experiments with CPMG detection.
AB  - We present a modified multiple-quantum (MQ) experiment, which implements the Carr
      Purcell-Meiboom-Gill (CPMG) detection scheme in the static MQ NMR experiment
      proposed by W. S. Warren et al. (1980, J. Chem. Phys.73, 2084-2099) and exploited
      further by O. N. Antzutkin and R. Tycko (1999, J. Chem. Phys.110, 2749-2752). It
      is demonstrated that a significant enhancement in the sensitivity can be achieved
      by acquiring echo trains in the MQ experiments for static powder samples. The
      modified scheme employing the CPMG detection was superior to the original MQ
      experiment, in particular for the carbonyl carbon with a very large chemical
      shift anisotropy.

PMID- 12202147
TI  - Two-dimensional NMR correlations of liquid crystals using switched angle
      spinning.
AB  - We present the first application of switched angle spinning (SAS) to correlate
      the first-order dipolar spectrum of a liquid crystalline sample with the
      isotropic magic angle spinning (MAS) spectrum in a two-dimensional experiment. In
      this experiment we are able to select the degree of dipolar couplings introduced
      via mechanical manipulations of the liquid crystal director in a single oriented
      sample. The (19)F SAS-COSY correlation of iodotrifluoroethylene, an AMX spin
      system, dissolved in the nematic liquid crystal 4-octylphenyl-2-chloro-4-(4
      heptylbenzoyloxy)-benzoate provides assignment of both the J and dipolar
      couplings in a single experiment. This work demonstrates the use of oriented
      samples and sample spinning to resolve homonuclear dipolar couplings using
      isotropic chemical shifts.

PMID- 12202148
TI  - Administration of proteolytic enzymes bromelain and trypsin diminish the number
      of CD4+ cells and the interferon-gamma response in Peyer's patches and spleen in
      endotoxemic balb/c mice.
AB  - Recent publications revealed that bromelain exerts a marked effect on T-cell
      response by inhibiting T-cell signal transduction. These experimental studies may
      help to explain former clinical investigations showing that Phlogenzym (PHL), a
      preparation consisting of the proteases bromelain and trypsin and the antioxidant
      rutosid, ameliorate certain diseases with an underlying inflammatory process. In
      this study, we showed that orally administered PHL significantly reduced
      lymphocyte subpopulations in Peyer's patches (PPs) of healthy and endotoxemic
      mice. Similarly, the number of splenic lymphocytes in endotoxin-boostered mice
      was significantly lowered by PHL. The effect of PHL was more pronounced on T
      cells than on B cells leading especially to a diminution of CD4+ cells. Moreover,
      PHL pretreatment decreased IFN-gamma mRNA in PPs and spleen of endotoxemic mice.
      These results reveal that PHL may ameliorate inflammatory process by reducing the
      number of CD4+ cells and by diminishing INF-gamma mRNA levels.

PMID- 12202149
TI  - Active cellular infection of myeloid cells is required for HIV-1-mediated
      suppression of interleukin-12 p40 expression.
AB  - Immunodeficiency during HIV infection is associated with impaired production of
      interleukin-12 (IL-12). Here we examine the requirement for active cellular
      infection, the role of other cytokines, and the molecular target of HIV-mediated
      suppression of IL-12. The reduction in LPS-induced IL-12 p40 protein and mRNA
      following acute in vitro HIV infection of THP-1 cells and monocytes was not
      attributed to IL-10 or TGF-beta activity and was not restored by priming with IL
      4, IL-13, or IFN-gamma. Suppression of IL-12 was dependent upon active cellular
      infection and replication and not due to any soluble host or viral factors in HIV
      infected cultures. Significant reduction in transcription of IL-12 p40 was
      observed following acute HIV infection. These results suggest that impaired IL-12
      production in HIV-infected myeloid cells occurs, in part, via disruption of IL-12
      p40 gene expression in a manner that requires cellular infection, highlighting
      the need to study myeloid cells in isolation during acute HIV-1 infection.

PMID- 12202150
TI  - CTLA-4 and autoimmune thyroid disease: lack of influence of the A49G signal
      peptide polymorphism on functional recombinant human CTLA-4.
AB  - A single nucleotide A49G polymorphism (SNP) of CTLA-4 has been linked and
      associated with the autoimmune thyroid diseases (AITD) and thyroid autoantibody
      secretion. We have explored the functional mechanisms of CTLA-4 by means of
      recombinant human CTLA-4 expressed on transfected Jurkat T cells. Analysis of
      CTLA-4 transcripts with quantitative real-time PCR demonstrated similar baseline
      and PHA-stimulated levels for both the A49 and G49 alleles, which were markedly
      enhanced by anti-CTLA-4 engagement. Both alleles also coded for proteins which
      were expressed on the cell membrane, as measured by FACS analysis using anti-CTLA
      4 (G: 34.4+/-11.9% cells, A: 27.6+/-8.6% cells) (p=ns). Baseline and PHA
      stimulated IL-2 production were also similar among control and CTLA-4 clones
      expressing both alleles. After anti-CTLA-4 engagement, IL-2 production was
      markedly inhibited in a dose- and time-dependent manner but this also appeared to
      be similar in the A and G allele expressing cells (95.7+/-1.2% inhibition and
      94.9+/-1.1% inhibition, respectively). In conclusion, both the extrinsic and
      intrinsic actions of human CTLA-4 were not affected by the signal peptide A49G
      polymorphism. Therefore, the linkage of the CTLA-4 A49G SNP to AITD is most
      likely secondary to linkage disequilibrium.

PMID- 12202151
TI  - Study of the physical meaning of the binding parameters involved in effector
      target conjugation using monoclonal antibodies against adhesion molecules and
      cholera toxin.
AB  - In earlier work, we established a mathematical model to characterize the binding
      properties of cytotoxic cells to target cells. These properties can be described
      by the values of the maximum effector and target conjugate frequencies,
      alpha(max) and beta(max), respectively, and the dissociation constant of the
      conjugates formed, K(D) (Garcia-Penarrubia, P., Cabrera, L., Alvarez, R., and
      Galvez, J., J. Immunol. Methods 155 (1992) 133). Here, we address the problem of
      exploring the physical meaning of these parameters and their relationships with
      cytotoxicity. With this purpose, conjugation between a human leukemic NK cell
      line (NKL) and K562 tumor cells has been studied from binding isotherms obtained
      from data of effector (alpha) and target (beta) conjugate frequencies measured by
      flow cytometry analysis at different effector-to-target ratios (R). The results
      have been compared to those obtained after target cells treatment with monoclonal
      antibodies recognizing adhesion molecules ICAM-1 (CD54) and LFA-3 (CD58) (which
      are able to block some of the receptors implicated in conjugation), as well as
      with cholera toxin (CTX) that can modify the state of affinity of some adhesion
      molecules such as LFA-1 (CD11a/CD18). The results show that: (1) blocking
      adhesion receptors CD54 and CD58 on the surface of target cells leads to a
      significant decrease of alpha(max) and beta(max), indicating that these
      parameters are related to the density of expression of receptors implicated in
      effector-target adhesion; (2) treatment of effector cells with CTX induced an
      increase of K(D), demonstrating that this parameter is associated with the
      effector-target affinity of the system; and (3) parallel experiments of
      conjugation and cytotoxicity showed that effector-target affinity and
      saturability influence the cytotoxic activity of the effector population.

PMID- 12202152
TI  - Oxidative stress is involved in the heat stress-induced downregulation of TCR
      zeta chain expression and TCR/CD3-mediated [Ca(2+)](i) response in human T
      lymphocytes.
AB  - Exposure of human T-lymphocytes to heat downregulates TCR zeta chain expression
      and inhibits (TCR)/CD3-mediated production of inositol triphosphate and
      [Ca(2+)](i) signaling. Here we investigated whether oxidative stress is involved
      in the heat-induced downregulation of TCR/CD3-mediated signaling. To this end, we
      have studied the effect of a thiol antioxidant, N-acetyl-L-cysteine (NAC), and a
      non-thiol antioxidant, allopurinol, on heat-induced downregulation of TCR/CD3
      mediated signaling. We found that preincubation of cells with 10mM NAC
      significantly reversed the downregulation of TCR/CD3-mediated [Ca(2+)](i)
      response and restored the suppression of TCR zeta chain protein expression as
      well as prevented its increased membrane distribution in heat-treated cells. NAC
      also reversed the downregulation of TCR zeta chain mRNA expression and the active
      94kDa TCR zeta chain transcription factor, Elf-1, in heat-treated cells.
      Consistent with the increase in the TCR zeta chain, preincubation with NAC
      increased the levels of antigen receptor-induced tyrosine phosphorylation of
      several cytosolic proteins. Finally, treatment with NAC was able to reverse the
      suppression of IL-2 production in heat-treated cells. Inactive analog, N
      acetylserine, failed to reverse the heat-induced downregulation of TCR/CD3
      mediated signaling. Allopurinol, another potent non-thiol antioxidant, also
      restored the TCR/CD3-mediated [Ca(2+)](i) response in heat-treated cells. These
      results demonstrate that antioxidants restore the expression of TCR zeta chain
      and reverse the TCR/CD3-mediated signaling abnormalities associated with heat
      stress and suggest that heat shock-induced oxidative stress is a mediator of the
      heat-induced biochemical damage that leads to downregulation of signaling in
      human T-lymphocytes.

PMID- 12202153
TI  - IL-10 alters DC function via modulation of cell surface molecules resulting in
      impaired T-cell responses.
AB  - IL-10 is a potent inhibitor of T-cell activation and has tolerizing effects on
      these cells. These effects are primarily mediated via modulation of antigen
      presenting cell function. Here, it is demonstrated that IL-10 completely inhibits
      LPS-induced DC maturation, resulting in altered DC-T-cell interactions and
      reduced T-cell responses. IL-10 inhibited LPS-induced upregulation of
      costimulatory molecules, MHC Class II, and the secretion of IL-12, TNF-alpha, IL
      6, and IL-1beta by DCs, although it upregulated the SLAM (CD150) expression at
      both the mRNA and protein levels. IL-10 pre-treated DC did not respond to
      subsequent LPS activation and its stimulatory ability for allogeneic and antigen
      specific T-cells was severely impaired. Importantly, T-cells derived from co
      cultures with Ag-pulsed, IL-10-treated DC were impaired in their responses to
      subsequent Ag-specific restimulation. Transwell and DC-derived plasma membrane
      experiments indicated that the capacity of IL-10-treated DC to induce T-cell
      unresponsiveness results from alterations in the cell surface molecules rather
      than modulation of cytokine secretion.

PMID- 12202154
TI  - Development of a transient CD4(+)CD8(+) T cell subset in the cervical lymph nodes
      following intratracheal instillation with an adenovirus vector.
AB  - Past studies have described the serendipitous appearance of peripheral
      CD4(+)CD8(+) double-positive (DP) T cells in both humans and nonhuman primates
      usually following a viral infection or resulting from a malignancy. However,
      understanding the role of DP T cells has been hampered by the lack of their
      reproducible generation. Herein, we describe DP T cells produced after a single
      intratracheal or intranasal dose of recombinant adenovirus 2 or 5 vector into
      mice. In a time-dependent fashion, DP T cells localized only in the deep cervical
      lymph nodes but not in the lungs or in any of the respiratory lymph nodes. These
      DP T cells were TCR(alpha)beta(+) and CD8(alpha)beta(+), but not
      TCR(gamma)delta(+) nor CD8(alpha)alpha(+), suggesting that these cells are
      unrelated to intestinally derived DP T cells. Upon co-stimulation with anti-CD3
      and anti-CD28, DP T cells showed increased expression of VLA-1, VLA-2, and CD69,
      and were more effective than CD4(+) T cells in T helper cell activity, as
      evidenced by increased IgA, IgG, and IgM production. Such co-stimulation also
      favored the production of IFN-gamma and IL-10 where CD4(+) T cells were more
      inclined to produce IFN-gamma and IL-2.

PMID- 12202155
TI  - Human peripheral blood monocyte-derived interleukin-10-induced semi-mature
      dendritic cells induce anergic CD4(+) and CD8(+) T cells via presentation of the
      internalized soluble antigen and cross-presentation of the phagocytosed necrotic
      cellular fragments.
AB  - We examined the ability of human monocyte-derived interleukin (IL)-10-induced
      semi-mature dendritic cells (semi-mDCs) that had been pulsed with soluble protein
      and necrotic cellular fragments to induce an antigen (Ag)-specific anergy in
      CD4(+) and CD8(+) T cells. IL-10 converted normal immature DCs (iDCs) into semi
      mDCs during the maturation. In contrast to normal iDCs and mature DCs, IL-10
      induced semi-mDCs as well as IL-10-treated iDCs not only had reduced their
      allogeneic T cell-stimulatory capacity, but also induced an allogeneic Ag
      specific anergy in T cells. Normal mDCs that had been pulsed with tetanus toxin
      (TT) or allogeneic necrotic cellular fragments caused further activation of TT
      specific CD4(+) T cells or allogeneic fibroblast-specific CD8(+) T cells, Ag
      pulsed IL-10-induced semi-mDCs induced an anergic state in both cell types. Thus,
      our results suggest that IL-10-induced semi-mDCs induce an Ag-specific anergy in
      CD4(+) and CD8(+) T cells via presentation of the internalized protein and cross
      presentation of the phagocytosed cellular fragments.

PMID- 12202156
TI  - Role of MAP kinase activation in Nramp1 mRNA stability in RAW264.7 macrophages
      expressing Nramp1(Gly169).
AB  - Nramp1 (natural resistance-associated macrophage protein 1) is a phagosomal iron
      transport molecule. In addition to its anti-microbial activity, Nramp1 exerts a
      wide range of pleiotropic effects, including increased stability of Nramp1 mRNA
      and a variety of other mRNA species. Previously, we showed that the increased
      stability of Nramp1 mRNA is regulated by an oxidant-generated signaling pathway
      that requires PKC. In the current study, we show that inhibition of ERK1,2 and
      p38 MAP kinase activities decreases Nramp1 mRNA stability in Mycobacterium avium
      infected RAW264.7 cells expressing Nramp1(Gly169) but not in RAW264.7
      Nramp1(Asp169) cells. Phosphorylation of ERK1,2 and p38 MAP kinases, which could
      be inhibited by the anti-oxidant BHA and a protein kinase C inhibitor, was higher
      in M. avium infected RAW264.7-Nramp1(Gly169) cells than in RAW26.47
      Nramp1(Asp169) cells. These results suggest that generation of oxidants by Nramp1
      iron transport activates MAP kinase signaling cascades that result in
      stabilization of Nramp1 mRNA.

PMID- 12202157
TI  - Assembly and cell surface expression of TAP-independent, chloroquine-sensitive
      and interferon-gamma-inducible class I MHC complexes in transformed fibroblast
      cell lines are regulated by tapasin.
AB  - Antigen processing and presentation by class I MHC molecules generally require
      assembly with peptide epitopes generated by the proteasome and transported into
      the ER by the transporters associated with antigen presentation (TAP). Recently,
      TAP-independent pathways supporting class I MHC-mediated presentation of
      exogenous antigens, as well as of endogenously synthesized viral antigens, were
      described. We now characterize a TAP-independent pathway that is operative in
      both TAP1- and TAP2-deficient Adenovirus (Ad)-transformed fibroblast cell lines.
      To the best of our knowledge, this is the first time that the existence of such a
      pathway has been described in non-infected cells that do not belong to the
      hematopoietic lineage. We show that this pathway is proteasome-independent and
      chloroquine-sensitive. Cell surface expression of these TAP-independent class I
      complexes is modulated by tapasin levels and is enhanced by IFN-gamma. The data
      imply that IFN-gamma increases the relative level of TAP-independent high
      affinity class I complexes that exit the ER on their way to the cell surface and
      to vacuolar compartments where peptide cleavage/exchange might take place before
      recycling to the cell surface. Since both TAP and tapasin expression are altered
      in numerous tumors and in virus-infected cells, TAP-independent class I complexes
      may be a valuable target source for immune responses.

PMID- 12202158
TI  - Ultrastructural examination of cytoskeletal linkage of L-selectin and comparison
      of L-selectin cytoskeletal association to that of other human and bovine
      lymphocyte surface antigens.
AB  - L-selectin is constitutively expressed on most leukocytes and is responsible for
      the initial events in cell trafficking termed tethering and rolling. Recently, L
      selectin has been shown to associate with the actin-based cytoskeleton under a
      variety of conditions. In an effort to better understand L-selectin cytoskeletal
      association and the ultrastructural nature of the cytoskeleton itself, we provide
      a comparison of the cytoskeletal association of various human and bovine surface
      proteins in relation to L-selectin. Electron microscopic examination of the
      cytoskeleton provided further data on the ultrastructure of freshly isolated
      peripheral lymphocytes as well as demonstrated L-selectin localization to the
      periphery of the cytoskeleton following low dose detergent treatment of the cell.
      Clusters of colloidal-gold-stained L-selectin were found on the surface of the
      detergent-treated lymphocytes, even though these particles completely lacked
      microvilli. By flow cytometry, we have defined three distinct patterns of
      cytoskeletal association; constitutive, inductive, and mAb crosslink-induced, and
      assigned human and bovine CD2, CD3, CD4, CD5, CD8, CD18, CD19, CD44, CD45RA,
      CD45RO, alphabeta TCR, gammadelta TCR, E-selectin ligands, and L-selectin surface
      antigens to one of these respective patterns. SDS-PAGE analyses confirmed most of
      the flow cytometry results. Depending upon its conformation, L-selectin fell into
      the inductive or mAb crosslink-induced pattern of association, similar to E
      selectin ligand(s). Our data provide additional insight into the functional role
      of L-selectin and the cytoskeleton in immunological events.

PMID- 12202159
TI  - The co-ordination of a RTD project at European level: difficulties and traps by
      the different steps.
AB  - When a scientist wants to set up and co-ordinate a Research and Technical
      Development (RTD) project for the first time, he is confronted with a certain
      number of factors, which, generally, are completely unknown. To co-ordinate a
      research project, it is not sufficient to have, as starting point, a set of
      interesting and innovative scientific themes. In fact, after the first
      preparatory steps, he is confronted with a number of difficulties such as the
      sinking of the project before it is put forward for financing. The different
      visions from the scientific and industrial partners are sometimes completely
      opposite (4): so it is necessary to understand and to assess the requirements of
      every participant. The industrial partner approach is, for example, linked to
      this assessment, bearing in mind that his involvement is indispensable for the
      viability of the project. First of all, this work aims to warn scientists who
      wish to start up in such an adventure, and secondly serve as a 'vademecum for the
      co-ordinator' in order to achieve successful completion of work that requires big
      investments in energy and time.

PMID- 12202160
TI  - Physicochemical principles of tissue material interactions.
AB  - Biocompatibility of a material has to be adapted to the specific properties of
      the locus of application that are the type of tissue and the composition of
      extracellular fluid or the blood being in contact with the surface. The
      biocompatibility is beyond that greatly influenced by the design of the medical
      device which has to be planned close to the material's properties and the
      function within the body. Physical chemical reactions at and physical properties
      of the surface which influence the adsorption behavior for biomacromolecules.
      Conformational or functional changes of f.i. proteins due to physical forces
      originating from the surface could be the communication messages to the
      immunological system. The immersion of a material into an aqueous electrolyte
      leads generally to a space charge layer on both sides of the interface forming
      the electrical double layer, physically described by the isoelectric point of the
      materials surface. A numerical example hints on the importance of the double
      layer structure for the 'communication' between an implant and the surrounding
      extracellular fluid including beside ions complex structured proteins as
      biomacromolecules. Biocompatibility depends on the physical structure of the
      material and physicochemical properties of the interface to the biosystem. The
      conductivity of the surface film control reactions across the interface with
      biomacromolecules of the biological environment. Conformational unchanged
      macromolecules are the prior condition for biocompatibility and controls the
      attachment and probably also the degree of attachment via adhesion proteins.
      Later on, when the cells develop tension through the cytoskeleton on these
      attachment sites, the strength of the integrin adhesion protein-matrix protein
      interaction might probably prove decisive in differentiation state of the cell.
      It has been proved by molecular biological methods that an undestroyed oxide
      layer of anatase on titanium through passivation leaves for instance albumin
      conformational unchanged.

PMID- 12202161
TI  - Surface properties of calcium phosphate particles for self setting bone cements.
AB  - Calcium phosphate cements (CPC), consist of multicomponent powder mixtures of
      calcium orthophosphates with grain sizes in the region of 1-20 microm. Due to the
      small particle sizes surface properties as the zeta potential and adsorption
      processes play a significant role during manufacturing and application. In the
      context of this work zeta potentials of different calcium phosphates, like
      dicalcium phosphate anhydride (DPCA) tetracalcium phosphate (TTCP) and
      hydroxyapatite were measured in various organic/aqueous media with different pH
      values. The results show a strong dependency of the zeta potential on the kind of
      suspension medium used associated with different milling properties. The addition
      of sodium phosphate leads to a pH value dependent stabilization of the particles
      in the liquid phase; the zeta potential of the surface increases from about -15
      to -18 mV in water and from -35 to -45 mV in 0.05 mol/l sodium phosphate
      solution. Besides the interaction of particles with various antibiotics was
      determined on the basis of the zeta potential of the surface. The substances
      partly cause a tremendous change of the surface load. This is accompanied by a
      change of the rheological properties of the cement paste, the morphology of the
      hardened cement matrix and a significant deterioration of the application
      relevant properties as setting time or mechanical strength.

PMID- 12202162
TI  - In vitro and in vivo tests of hydrothermally synthesised hydroxyapatite coating.
AB  - High pure and crystalline Hydroxyapatite (HA) coatings on titanium alloy were
      prepared by hydrothermal synthesis (HS) of plasma-sprayed (PS) precursors from
      brushite powders (HS-HA). In vitro and in vivo tests were done to evaluate its
      biological property. The HS-HA coating was compared with the current PS-HA
      coating. Cultures of the primary osteoblasts on these two HA coatings showed
      similar cell attachment, proliferation and alkaline phosphatase (ALP) expression.
      The cell morphology on the coatings was demonstrated by scanning electron
      microscopy (SEM). The cell spread well at 1 day after seeding culture and the
      extracellular matrix was secreted after 14 days culture. Histomorphometric
      analysis was conducted on samples implanted in femoral bone of four dogs for 1
      and 3 months, and bone-implant contact percentage was evaluated by light
      microscopy. The calcium and phosphate distribution on the interface of bone
      implant was analysed by SEM and electron dispersive X-ray (EDX) analysis. The
      results show the osteoconduction of HS-HA coated implants.

PMID- 12202163
TI  - Microstructural study of aerosol-gel derived hydroxyapatite coatings.
AB  - Highly porous aerosol-gel derived hydroxyapatite (HAP) coatings have been
      prepared from calcium nitrate and phosphoric acid based sols. Precursor solutions
      were prepared by filtering the suspension formed during the ultrasonic slurring
      of the reactants mixture. The coatings deposited on Si wafers were studied after
      sintering at different temperatures by using Fourier transform infrared
      spectroscopy, X-ray diffraction, energy disperse microanalysis and scanning
      electron microscopy. The composition, structure and morphology of the coatings
      sintered at 650 degrees C were found to fit highly porous HAP. That is considered
      of great relevance since the deposition parameters are compatible with the
      processing of bioactive coatings on load bearing metallic substrates.

PMID- 12202164
TI  - Investigation of interfacial capacitance of Pt, Ti and TiN coated electrodes by
      electrochemical impedance spectroscopy.
AB  - Electrochemical processes at the electrode-electrolyte (body fluid) interface are
      of ultimate importance for stimulating/sensing electrode function. A high
      electrode surface area is desirable for safe stimulation through double-layer
      charging and discharging. Pt and Pt-Ir alloys have been the most common electrode
      materials. The use of TiN coating as the surface layer on the electrode has found
      increasing interest because of its metal-like conductivity, excellent mechanical
      and chemical properties, and the fact that it can be deposited with a high
      surface area. In this work, electrochemical impedance spectroscopy (EIS), which
      is a sensitive and non-destructive technique and widely used for characterization
      of electrical properties of electrode-electrolyte interfaces, was applied to
      investigate pure Pt and Ti, and TiN coated electrodes exposed to a phosphate
      buffered-saline (PBS) solution. Platinized Pt and Ti were also studied for
      comparison. The capacitance value of the electrodes in PBS was obtained through
      quantitative analysis of the EIS spectra. The results reveal that the capacitance
      of the TiN coated electrodes with a rough surface is several hundreds times
      higher than that of a smooth Pt surface. Platinization of Ti can also increase
      the capacitance to the same extent as platina. EIS has been shown to be a
      powerful technique for characterization of stimulating/sensing electrodes.

PMID- 12202165
TI  - Non-destructive three-dimensional evaluation of a polymer sponge by micro
      tomography using synchrotron radiation.
AB  - X-ray micro-tomography, a non-destructive technique is used to uncover the
      complex 3-D micro-architecture of a degradable polymer sponge designed for bone
      augmentation. The measurements performed at HASYLAB at DESY are based on a
      synchrotron radiation source resulting in a spatial resolution of about 5.4
      microm. In the present communication we report the quantitative analysis of the
      porosity and of the pore architecture. First, we elucidate that synchrotron
      radiation at the photon energy of 9 keV has an appropriate cross section for this
      low-weight material. Modifications in sponge micro-architecture during
      measurement are not detected. Second, the treatment of the data, an amount of 2.5
      Gbyte to generate binary data is described. We compare the 3-D with the 2-D
      analysis in a quantitative manner. The obtained values for the mean distance to
      material within the sponge calculated from 2-D and 3-D data of the whole tomogram
      differ significantly: 12.5 microm for 3-D and 17.6 microm for 2-D analysis. If
      the pores exhibit a spherical shape as frequently found, the derived mean pore
      diameter, however, is overestimated only by 6% in the 2-D image analysis with
      respect to the 3-D evaluation. This approach can be applied to different porous
      biomaterials and composites even in a hydrated state close to physiological
      conditions, where any surface preparation artifact is avoided.

PMID- 12202166
TI  - An unscaled parameter to measure the order of surfaces: a new surface elaboration
      to increase cells adhesion.
AB  - We present a new parameter to quantify the order of a surface. This parameter is
      scale-independent and can be used to compare the organization of a surface at
      different scales of range and amplitude. To test the accuracy of this roughness
      parameter versus a hundred existing ones, we created an original statistical
      bootstrap method. In order to assess the physical relevance of this new
      parameter, we elaborated a great number of surfaces with various roughness
      amplitudes on titanium and titanium-based alloys using different physical
      processes. Then we studied the influence of the roughness amplitude on in vitro
      adhesion and proliferation of human osteoblasts. It was then shown that our new
      parameter best discriminates among the cell adhesion phenomena than others'
      parameters (Average roughness (Ra em leader )): cells adhere better on isotropic
      surfaces with a low order, provided this order is quantified on a scale that is
      more important than that of the cells. Additionally, on these low ordered
      metallic surfaces, the shape of the cells presents the same morphological aspect
      as that we can see on the human bone trabeculae. The method used to prepare these
      isotropic surfaces (electroerosion) could be undoubtedly and easily applied to
      prepare most biomaterials with complex geometries and to improve bone implant
      integration. Moreover, the new order parameter we developed may be particularly
      useful for the fundamental understanding of the mechanism of bone cell
      installation on a relief and of the formation of bone cell-material interface.

PMID- 12202167
TI  - Human serum albumin adsorption onto a-SiC:H and a-C:H thin films deposited by
      plasma enhanced chemical vapor deposition.
AB  - In the present paper, we report the study of the adsorption behavior of a model
      protein such as human serum albumin (HSA) onto surfaces of a-SiC:H and a-C:H thin
      films deposited by using the plasma-enhanced chemical vapor deposition (PECVD)
      technique. The surface composition and surface energy of the various substrates
      as well as the evaluation of the adsorbed amount of protein has been carried out
      by means of X-ray photoelectron spectroscopy (XPS) and contact angle
      measurements. It has been found that HSA tends to preferentially adsorb on Si
      rich surfaces, as far as the relative amount of adsorbed HSA decreases with
      increasing S-C concentration. Preliminary elements of mechanistic models are
      proposed for the correlation between chemical factors and the observed protein
      adsorption behavior.

PMID- 12202168
TI  - In vitro hemocompatibility testing of biomaterials according to the ISO 10993-4.
AB  - The development of synthetic materials, textured polymers and metals and their
      increasing use in medicine make research of biomaterials' hemocompatibility very
      relevant. Problems arise from the polymorphism and diversity of the different
      materials, the static and dynamic test models and the patients' individual
      biologic factors. First, methods, models, tests as well as preanalytical factors
      have to be standardized according to the current knowledge in medicine laid down
      in the ISO 10993 part 4. The routine controls used in clinical chemistry and
      hematology have to be performed. Information about normal ranges (mean value,
      standard deviation, 95% confidence interval) should be provided. Tests have to be
      performed within a minimal delay of usually 2 h since some properties of blood
      change rapidly following collection. Various conditions (depending on the wall
      shear rate) were simulated within the centrifugation system and a Chandler
      system. Qualities and aspects of hemocompatibility such as platelet activation,
      oxidative burst, hemolysis, fibrinolysis, fibrin formation, generation of
      thrombin, contact activation, and complement activation were analysed and the
      results were entered non-dimensionally into a non-dimensional score system, where
      0 points stand for the best and 65 points for the worst evaluation. We found a
      good correlation between the total score and contact activation, thrombin
      generation and leukocyte activation in a low shear stress system and a good
      correlation between the total score and thrombin generation, hemolysis and
      platelet activation in the high shear stress system. Further on the effect of
      additives and sterilization procedures can be measured. The concepts presented
      underline the relevance/importance of an efficient diagnostic approach to
      hemocompatibility that takes account of clinical and socio-economic concerns.

PMID- 12202169
TI  - Evaluation of the haemocompatibility of titanium based biomaterials.
AB  - The increased use of metallic biomaterials in contact with blood e.g. for the
      application as coronary stents leads to the development of new biomaterials. The
      main requirements for stents are high flexibility, high cold deformability and
      sufficient mechanical strength (static and dynamic), which can be obtained by
      strain hardening, radio-opacity and haemocompatibility. In order to investigate
      the properties of the metallic biomaterials in contact with blood, a comparison
      of the haemocompatibility of newly developed materials with established materials
      has been performed. To evaluate haemocompatibility without the influence of the
      geometry of the material, spherical powders produced by rotating electrode
      process (REP) were used in a dynamic test system with full human blood under two
      different stress conditions. The high shear stress simulates the arterial and the
      low shear stress simulates the venous situation. The use of a dimensionless score
      point (SP) system where the parameters of the haemocompatibility are determined
      with and without a material exposition allows an objective comparison of the
      materials used.

PMID- 12202170
TI  - Multiple parameter cytotoxicity index on dental alloys and pure metals.
AB  - Palladium (Pd) is a metal frequently used for dental alloys. In order to
      elucidate controversial options about Pd concerning its biological performances,
      our study consists in the evaluation of commercial and experimental PFM and C&B
      precious and semi-precious dental alloys. This investigation was also designated
      to the establishment of a cytotoxicity index (CI) such as it was described for
      hemocompatibility testing. The following materials were tested: 36 commercial
      alloys (Au-, Pd- and Ag-base), 14 experimental alloys (Pd-base established by an
      experience plan) and pure metals (Ag, Au, Cu, Ni, Cr, In, Sn, Pt, Ti, Zn). The
      cells culture experiments were carried out with epithelial L132 cells and NIH 3T3
      fibroblasts. In vitro cell viability tests show that Pt, Sn, In, Ti, Au and Pd
      have no cytotoxic effect; Cr, Cu and Ag are toxic, Ni, Zn, and Co are highly
      toxic. An identical ranking was found with the inflammatory and proliferation
      tests. Toxic and highly toxic metals induced slight or strong prosthetic dental
      restoration morphological alterations after 3-days cultures and mostly cell death
      after 6-days cultures. These effects are dependent on the leakage of the element
      into the culture medium as revealed by ICP. The addition of Au gives benefit to
      Pd-Ag alloys, but does not produce any major effect on Pd-Cu alloys. This
      qualitative ranking can quantitatively be confirmed by cytocompatibility testing
      after application of a CI.

PMID- 12202171
TI  - Growth of osteoblast-like cells on porous hydroxyapatite ceramics: an in vitro
      study.
AB  - Blocks of two porous synthetic hydroxyapatites (HA) with porosity fraction of 30
      40 and 50-60 vol%, respectively and a coralline derived porous HA were evaluated
      in vitro in presence of the osteogenic line MC3T3-E1 and of L929 fibroblasts. The
      two tested biomaterials did not affect cellular proliferation (MTT test), but the
      contact inhibited alkaline phosphatase activity. Porous aggregates resulted
      perfectly biocompatible in the tests performed, since observations performed by
      light microscopy did not show any cell morphological change, osteoblast presented
      a stellar shape and typical pseudopodes. SEM observations showed intercellular
      matrix containing fibers on HA-based porous aggregates.

PMID- 12202172
TI  - Long term tissue response to titanium coated with diamond like carbon.
AB  - Diamond like carbon (DLC) coatings were deposited on to Ti substrates by plasma
      enhanced chemical vapor deposition technique. Ti and DLC/Ti samples were
      implanted in skeletal muscle of rabbits. The samples were explanted after 1, 3, 6
      and 12 months and the tissue-cell interaction was studied. Our data indicate both
      DLC/Ti and bare Ti to be compatible with skeletal muscle.

PMID- 12202173
TI  - Investigation on plasma immersion ion implantation treated medical implants.
AB  - In this work the biocompatibility of osteosynsthesis plates treated with plasma
      immersion ion implantation (PIII) was tested using a rat model. Small rods (O 0.9
      mm, and length 10 mm) prepared from different materials-pure Ti, anodised Ti, and
      two NiTi alloys (SE 508, and SM 495)-were implanted with oxygen by PIII to form a
      rutile surface layer and subsequently inserted into rat femurs, together with a
      control group of untreated samples. The results of the biomechanical tests
      correlate with the histological results, and show that plasma immersion ion
      implantation leads to an increase of biocompatibility and osseointegration of
      titanium and NiTi, albeit no improvement of the (bad) biocompatibility of the
      anodised Ti. Despite the layer thickness of up to 0.5 microm a strong influence
      of the base material is still present.

PMID- 12202174
TI  - In vitro MC3T3 osteoblast adhesion with respect to surface roughness of Ti6Al4V
      substrates.
AB  - This work investigates the role of the surface roughness of Ti6Al4V on the cell
      morphology, proliferation and adhesion, and in particular on the variation of the
      expression of cell adhesion proteins. Standardised test samples with five
      different surface preparations are used: sandblasted, 80, 1200, and 4000 grade
      polished, mirror polished. Surface roughness is analysed by Scanning Electron
      Microscopy and LASER Confocal Microscopy. Cell culture experiments are performed
      with MC3T3-E1 mouse osteoblasts after 3 days culture: proliferation rate,
      morphology and adhesion are assessed. The variations of expression of cell
      adhesion proteins are evidenced by indirect immune fluorescence method: actin
      from the cytoskeleton, vinculin from the focal adhesion complex, fibronectin and
      collagen I from the extracellular matrix. The results reveal a clear influence of
      surface roughness of Ti6Al4V on cell proliferation, morphology and adhesion. A
      significant correlation is established between surface roughness and cell growth.
      More the surface is smooth more the osteoblasts proliferate and appear spread out
      on the test samples. In addition, the expression of adhesion proteins varies with
      respect to the surface roughness. These results indicate a direct relationship
      between the decrease of cell adhesion and the increase of cell proliferation on
      mirror polished materials.

PMID- 12202175
TI  - In vitro studies of human and rat osteoclast activity on hydroxyapatite, beta
      tricalcium phosphate, calcium carbonate.
AB  - Investigations on the ceramic degradation caused by osteoclasts are designed to
      assess osteoclast-ceramic interactions and to determine which ceramics are more
      suitable for use as bone substitute. This study investigated the resorptive
      activity of osteoclasts on ceramics presenting different solubility rates.
      Osteoclasts isolated from new-born rat and from human giant cell tumour were
      cultured on different bioceramics: hydroxyapatite (HA), beta-tricalcium phosphate
      (TCP) and calcium carbonate (calcite). Cytoskeletal was revealed by actin
      labelling and ceramic surfaces were observed by scanning electron microscopy
      (SEM). On all materials, the distribution of actin in typical ring was revealed.
      SEM examinations showed a clear difference in the shape and the depth of
      resorption lacunae on different ceramics. On pure HA, a superficial attack,
      clearly visible but very little extended. Numerous resorption lacunae, deep and
      well-delimited were observed on pure beta-TCP, but attacks less punctually were
      detected too. On pure calcite, an attack with form of spikes, very widespread but
      superficial was revealed. Degradation measurements revealed a significant
      increase of P release from the phosphocalcic ceramics and of Ca from all ceramics
      in the presence of osteoclasts. The both cell models found these characteristics,
      the rat osteoclasts were also an excellent model to study the ceramic resorption.

PMID- 12202176
TI  - Electrochemical and cytocompatibility assessment of NiTiNOL memory shape alloy
      for orthodontic use.
AB  - Orthodontic arcs and wires are mostly realised from alloys and constitute the
      motor of dental shifting. Ti-base alloys rapidly replaced the formerly used
      stainless steel wires due to their excellent corrosion resistance, their high
      mechanical characteristics and their increased biocompatibility. NiTiNOL shape
      memory alloys add to these advantages their ability of deforming force. NiTiNOL,
      highly pure Nickel (hp-Ni) and commercially pure titanium (cp-Ti) were tested by
      electrochemical assays in artificial saliva and in vitro biological tests with
      L132 cells and HEPM cells. All tests gave concordant results: the electrochemical
      assays, the proliferation test, the colony forming method, and the inflammatory
      test clearly show, that nickel is a corrosive and a cytotoxic material. Ti and
      NiTiNOL are cytocompatible and in particular corrosion resistant. No significant
      differences are observed for both materials on the electrochemical and the
      biological level as well. The NiTiNOL shape memory alloy is a master trump for
      dental practitioners to repair occlusal defects by shifting teeth under optimal
      biological conditions. In spite of its high Ni-content, it is biocompatible. It
      considerably reduces the tune of therapeutic treatment, facilitate the occlusal
      concept and leads to a result of high clinical quality.

PMID- 12202177
TI  - Micropatterned surfaces for the control of endothelial cell behaviour.
AB  - Micropatterned materials were synthesised by photoimmobilising the sulphated
      hyaluronic acid, adequately functionalised with a photoreactive moiety, on glass
      substrates. Four different patterns (10, 25, 50 and 100 microns) were obtained.
      The spectroscopic and microscopic analysis of the microstructured surfaces
      revealed that the photoimmobilisation process was successful, demonstrating that
      the photomask was well reproduced on the sample surface. Analysis of endothelial
      cell behaviour on these micropatterned materials was performed in terms of
      adhesion, locomotion and orientation. Decreasing the stripe dimensions a more
      fusiform shape of the adhered endothelial cells was observed. At the same time
      the cell locomotion and orientation were increased. Furthermore, a
      photoimmobilisation of stripes of HyalS (10 and 100 microns) was performed on a
      continuous HyalS layer, in turn immobilised on glass substrate. Being excluded a
      different chemistry between the stripe and the substrate, the influence of
      topography on the behaviour of endothelia cells was thus envisaged.

PMID- 12202178
TI  - The effect of surface chemistry and structure of titanium nitride (TiN) films on
      primary hippocampal cells.
AB  - Thin films of TiN were investigated as a candidate microelectrode material for
      multi-electrode arrays, which are used for recording from electrically active
      cells in culture. TiN films were deposited onto glass substrates by DC pulsed
      reactive magnetron sputtering. The structure, phase composition and surface
      chemistry were studied using X-ray diffraction (XRD), Atomic force microscopy
      (AFM) and X-ray photoelectron spectroscopy (XPS). The biocompatibility of the TiN
      films was examined morphologically by monitoring neuronal network formation and
      comparing this to a control substrate. Results indicate that neuronal cell
      adhesion and growth is influenced by the surface chemistry and associated crystal
      orientation of the TiN thin films.

PMID- 12202179
TI  - Minimization of protein adsorption on poly(vinylidene fluoride).
AB  - Surfaces covered with polyethylene glycol (PEG) have been shown to be
      biocompatible because PEG yields nonimmunogenicity, nonantigenicity and protein
      rejection. To produce a biocompatible surface coating, we have developed a method
      for grafting PEG onto modified poly(vinylidene fluoride) (PVDF) films. The first
      step was to create carboxy groups on the PVDF surface following covalente
      coupling of polyethylenimine (PEI) to achieve high density of amino groups. These
      surface amines were reacted with formyl-terminated PEG's with various molecular
      weight. The modified PVDF surface was characterized by means of static contact
      angle measurements, infrared (IR) spectroscopy and X-ray photoelectron
      spectroscopy (XPS). The influence of the chain length on lysozyme repellence was
      investigated by means of surface-MALDI-Tof mass spectrometry (Surface-MALDI-Tof
      MS). Lysozyme adsorption was significantly suppressed on the PEG 5000 modified
      PVDF surface.

PMID- 12202180
TI  - Investigating specific antigen/antibody binding with the atomic force microscope.
AB  - The aim of this work is to detect immune complexes without any kind of labelling
      of each of the immunological species, with a view to create a very sensitive
      biosensor. This is achieved by using the atomic force microscopy. We have
      proceeded by imaging the antibody (anti-rabbit IgG) or anti-rabbit IgG moieties
      adsorbed onto mica surface, before and after incubation of two kinds of antigens:
      a specific (rabbit IgG) and a non-specific one (sheep IgG). The analysis using
      the height histograms reveals many interesting features. We propose a general
      framework for interpreting these analysis, which enables the discrimination
      between specific and non-specific complexes.

PMID- 12202181
TI  - Red blood cells imaging and antigen-antibody interaction measurement.
AB  - In the present study the atomic force microscope (AFM) was used to image the
      surface morphology of red blood cells (RBC) for the first time. The AFM yielded
      very reproducible images without appreciable modifications of the sample
      surfaces. In addition to this topographical imaging, we have developed an
      experimental approach to measure the binding strength between antibody (anti-A),
      and the RBC antigen A, when reversible bonds between specific molecules such as
      antigen and antibody mediate the adhesion. The experimental results suggest that
      the procedure established here may be used for specific antibody detection. This
      study has also enhanced our understanding under physiological conditions of
      molecular interaction in particular antigen-antibody.

PMID- 12202182
TI  - Characterization of glucose oxidase immobilization onto mica carrier by atomic
      force microscopy and kinetic studies.
AB  - Glucose oxidase (E.C 1.1.3.4) immobilized onto activated surface of mica was
      analyzed by enzymatic kinetics and visualization with atomic force microscopy
      (AFM). The activity of the immobilized enzyme decreased with the decrease of
      concentration of gamma-aminopropyltrimethoxysilane used for the first step of
      activation of mica, while AFM analysis showed similar homogeneous filling of the
      surface with the enzyme. The comparison of enzyme activity with its surface
      filling revealed that there has to be additional vertical structures, which
      cannot be visualized by the methods of AFM. The simultaneous decrease of the
      silanizing agent and the concentration of the enzyme led to molecular resolution
      for the enzyme on the surface of mica. This allows to propose the described
      method also for analyzing other surfaces of solid materials with coupled
      biomolecules.

PMID- 12202183
TI  - H-bonding in liquid N-methylformamide as studied by X-ray scattering.
AB  - A structural investigation of liquid N-methylformamide, C(2)H(5)NO, was performed
      at room temperature and atmospheric pressure using X-ray scattering. Experimental
      data are analysed to yield the molecular structure factor and the distinct pair
      correlation function. The more dominant form (cis or trans) is considered and the
      H-bonding parameters are deduced. In order to describe the local arrangement in
      the liquid, different models are examined.

PMID- 12202184
TI  - Water-silica gel interactions, X-ray diffraction study at room and low
      temperature.
AB  - X-ray diffraction experiments on water confined in silica gel powder hydrated at
      about 20% are presented and analyzed at room temperature and down to 77 K. The
      structural modification of confined water observed at second neighbors is due to
      the competition between the confinement effect and the water-silica interaction.

PMID- 12202185
TI  - Tissue response and biomaterial integration: the efficacy of in vitro methods.
AB  - Implantation involves tissue trauma, which evokes an inflammatory response,
      coupled to a wound healing reaction, involving angiogenesis, fibroblast
      activation and matrix remodelling. Until now the type and extent of such
      reactions to give optimal integration of various biomaterials are practically
      unknown. Three principal fields of research can yield useful data to understand
      these phenomena better: studies on explanted biomaterials, animal models and
      relevant in vitro techniques. This paper will present examples of the latter
      field and the application of endothelial cell (EC) culture systems to study the
      effects of important tissue (e.g. pro-inflammatory cytokines, chemokines) and
      material (e.g. metal ions, particulate debris) factors on the regulation of the
      inflammatory and angiogenic response. A central feature is the use of
      microvascular endothelial cells (MEC), which can be used in both 2-and 3
      dimensional (3-D) assays. We have also used genetic manipulation to develop a
      permanent MEC line from the human lung (HPMEC-ST1), which is being tested for its
      suitability to study cell-biomaterial interactions. In addition, suitable in
      vitro techniques are being developed in order to investigate drug delivery
      systems (DDS). Of particular interest is the targeting of the central nervous
      system, our approach being to establish a human model of the blood-brain barrier
      (BBB). A mainstay of our scientific philosophy is that such in vitro methods can
      make an important contribution to understanding biological reactions at the
      tissue-biomaterial interface and thus further a causal approach to tissue
      engineering (TE) and drug delivery applications.

PMID- 12202186
TI  - Cells under stress: a non-destructive evaluation of adhesion by ultrasounds.
AB  - The adhesion process plays a major role in the development of osteoblastic cells
      on various substrates used in orthopaedic applications such as metals,
      bioceramics, or glass. High frequency and low power ultrasounds seem to be an
      appropriate tool for an evaluation of interface mechanical properties. Is it a
      non-destructive method? We investigated osteoblastic cell cultures, maintained in
      their medium with high frequency, bulk longitudinal waves. The influence of both
      acoustical frequency and acoustical power on cell adhesion is evaluated by cell
      detachment ratio and re-adhesion ratio. We demonstrate the existence of a power
      threshold depending on the frequency, allowing optimal cellular detachment and re
      adhesion. Finally, a qualitative study of the detachment phenomena is performed
      by use of scanning electron microscopy (SEM), Confocal Laser Scanning Microscopy
      and cytochemical labelling.

PMID- 12202187
TI  - Influence of osteocalcin and collagen I on the mechanical and biological
      properties of Biocement D.
AB  - In order to generate a calcium-phosphate bone cement as a transient replacement
      for bone defects, we modified Biocement D (Merck Biomaterial GmbH) containing
      mineralised collagen with osteocalcin, the most abundant non-collageneous protein
      of bone. Osteocalcin was added to the cement paste during setting in order to
      control the crystallisation kinetics of hydroxyapatite (HAP) as well as to
      stimulate the interaction of osteoblasts and osteoclasts with the bone
      replacement material. Analysis by SEM and AFM shows, that the addition of
      osteocalcin causes a nanosize microstructure of the calcium cement, which can be
      explained by inhibited growth of HAP crystals. The fracture strength of the
      material decreased by incorporation of osteocalcin, pointing onto a higher defect
      concentration of the crystalline structure. The impact of osteocalcin onto the
      interaction of bone cells with HAP-Collagen I-cements was studied in a cell
      culture system using the human osteosarcoma cell line SAOS-2. Results suggest,
      that osteocalcin might possibly improve the initial adherence of osteoblast-like
      cells, whereas proliferation of the cells is not effected.

PMID- 12202188
TI  - Cell orientation and cytoskeleton organisation on ground titanium surfaces.
AB  - A stable connection between the biomaterial surface and the surrounding tissue is
      one of the most important prerequisites for the long-term success of implants.
      Therefore, a strong adhesion of the cells on the biomaterial surface is required.
      Beside the surface composition the surface topography influences the properties
      of the adherent cells. The quality of the connection between the cell and the
      biomaterial is-among other factors-determined by the dimensions of the surface
      topography. Osteoblasts and fibroblast-like cells in contact with a ground
      biomaterial surface spread in the direction of the surface structures. These
      aligned cells provide a more favourable adhesion behaviour than a spherically
      shaped cell. To determine the influence of the surface structure on the cell
      alignment and cytoskeleton organisation or arrangement, substrate discs of cp
      titanium were ground, producing different roughness of the substrates. The
      oriented cells had a higher density of focal contacts when they were in contact
      with the edges of the grooves and showed a better organisation of the
      cytoskeleton and stronger actin fibres. These changes of the aligned cells depend
      on the peak to valley height of the surface structures.

PMID- 12202189
TI  - Testing biomaterials by the in-situ evaluation of cell response.
AB  - In this work, we describe a technique for the in-situ observation of cells
      adhered on opaque biomaterial surfaces. The visualisation of the morphology of
      cells adhered onto a surface allows to derive nuclear apoptotic signs or even the
      existence of organisation between groups of these cells. The technique is based
      on the use of an auto-immune reaction combined with a fluorescent agent that
      allows a direct inspection of the cell behaviour. The versatility of the
      technique is demonstrated by presenting several examples with different cultured
      cells (human chondrosarcome cells (CSRCs) and pluripotential mesenchymal stem
      cells (MSCs) from bone marrow) seeded over two different Ti-based surfaces
      (TiO(2) and TiN, respectively). These in-vitro observations are compared with the
      behaviour of the same cells on bare TiAlV alloy. From our results it is concluded
      that both TiO(2) and TiN surfaces show enhanced biological responses.

PMID- 12202190
TI  - Interactions between cells and titanium surfaces.
AB  - The interaction between cells and implant materials is determined by the surface
      structure and/or surface composition of the material. In the past years, titanium
      and titanium alloys have proved their superiority over other implant materials in
      many clinical applications. This predominant behaviour is caused by a dense
      passive oxide layer which forms within milliseconds in oxidizing media. Titanium
      dioxide layers of 100 nm thickness were produced on the surface of cp-titanium
      grade 2, and on an experimental alloy of high vanadium content (Ti1.5Al25V) as a
      harmful control. The layers were produced by thermal and anodic oxidation and by
      coating by means of the sol-gel process. The resulting oxide layers were
      characterized with respect of their structure and chemical composition. In cell
      tests (proliferation, MTT, morphology, actin staining), the reaction of the cells
      was examined. It was shown that the sol-gel-produced titanium oxide layer is able
      to shield the cells from toxic alloying elements, with the result that the cell
      reaction is influenced only by the thin titanium oxide surface layer and not by
      the composition of the bulk material.

PMID- 12202191
TI  - Quantitation of platelet adhesion to Ti and DLC-coated Ti in vitro using (125)I
      labeled platelets.
AB  - Measurement of platelet adhesion in vitro is a good indicator of its reactivity
      to implant devices in vivo. Platelets were labeled with I-125 without affecting
      its normal morphology and function and the labeled platelets were suspended in
      platelet poor plasma and exposed to Ti and diamond like carbon-coated (DLC) Ti
      discs, under dynamic conditions, using a parallel plate flow chamber. The test
      materials were washed, dried, exposed to a phosphor screen and scanned to get the
      images. The number of platelets that adhered to Ti was found to be higher than
      those that adhered to DLC coated Ti sample, irrespective of the shear stress
      which was varied between 2 and 16 dynes/cm(2).

PMID- 12202192
TI  - Cell-extracellular matrix interaction and physico-chemical characteristics of
      titanium surfaces depend on the roughness of the material.
AB  - The interaction of cells with the extracellular matrix at the interface of an
      implant determines the biology of cells and tissues. We analysed components of
      cell adhesion and measured physico-chemical characteristics of structural
      modifications of titanium surfaces: polished, machined, glass particle-blasted,
      corundum-blasted, vacuum plasma-sprayed. Scanning electron microscopy and
      profilometry revealed a differentiated topography from smooth to rough surfaces,
      respectively. Osteoblastic MG-63 cells showed an increased spreading on surfaces
      with low roughness, although without a straight correlation with the surface
      topography. Integrin expression was increased on structured surfaces compared
      with polished material, and the organization of the actin cytoskeleton and
      fibronectin was impaired on extremely rough surfaces. Electrochemical methods,
      especially the electrochemical impedance spectroscopy (EIS) was used to evaluate
      physico-chemical characteristics, and the impedance curves revealed a dependence
      on the roughness of the material surfaces. Further analyses of the EIS results
      were performed using equivalent circuits which model the electrical flow through
      the interface. First indications for a correlation between parameters from the
      equivalent circuits with surface properties were obtained which promise a
      relevance for the biological response of the cells.

PMID- 12202193
TI  - Surface implantation treatments to prevent infection complications in short term
      devices.
AB  - Surface treatments of short term devices are actually evaluated to reduce the
      risk of infections, which in particular are one of the main causes of
      complications following catheter insertion. We have investigated the efficacy of
      ion beam techniques to reduce bacterial adhesion-or to induce bactericidal
      activity of different polymer materials: PVC, silicone rubber, poly(urethane) and
      poly(ethylene). Two routes have been evaluated, based on the production of non
      fouling surfaces, through the production of diamond-like surfaces upon
      irradiation with rare gases, or the implantation of silver, known for its
      bactericidal action. In this contribution we discuss more specifically the
      treatment of poly(ethylene), where a broad range of surface characterisation
      techniques could show that the biological activity resulted from the formation of
      metallic colloidal silver near the surface of the polymer, associated to the
      formation of a dense surface acting as a diffusion barrier. Reduction of the
      implantation energy to 10 keV, led to activity enhancement resulting from the
      easier accessibility of surface colloids evidenced by AFM microscopy. This study
      emphasises the specific processes induced by the formation of silver nano
      particles at low energy implantation, which differs basically from Ion Beam
      Assisted Deposition (IBAD technique) leading to the formation of a continuous
      silver coating (Artif. Organs 18 (1994) 266; International Patent (PCT) WO
      95/18637 (1995)).

PMID- 12202194
TI  - Ion beam treatment of titanium surfaces for enhancing deposition of
      hydroxyapatite from solution.
AB  - Surface coating with hydroxyapatite (HA) is a common way to improve the
      osseointegration of orthopaedic and dental titanium (Ti)-based materials. The
      main problems with current techniques are changes in composition during heating
      and poor adhesion to the surface. An alternative method is deposition of HA onto
      an activated surface out of a solution. The present work studies the surface
      treatment involving ion implantation of Na into Ti to induce a modification in
      chemistry and morphology, showing sodium titanate (Na(2)TiO(3)) incorporated
      within the surface layer with concentration, depth distribution, and morphology
      depending on the parameters of the ion implantation. Such ion-implanted Ti
      surfaces actively induce heterogeneous precipitation of HA from a simulated body
      fluid containing physiological concentrations of calcium and phosphate ions. This
      is compared with the activation by NaOH etching. The growth of bone forming cells
      on the pure Na implanted surface is oriented without an increased bone formation.
      Cell growth on the NaOH etched surface is reduced. After deposition of HA on both
      surfaces cell the growth pattern was improved.

PMID- 12202195
TI  - Protein adsorption onto auto-assembled polyelectrolyte films.
AB  - Surface modification by deposition of ordered protein systems constitutes one of
      the major objectives of bio-related chemistry and biotechnology. In this respect
      a concept has recently been reported aimed at fabricating multilayers by the
      consecutive adsorption of positively and negatively charged polyelectrolytes. We
      investigate the adsorption processes between polyelectrolyte multilayers and a
      series of positively and negatively charged proteins. The film buildup and
      adsorption experiments were followed by Scanning Angle Reflectometry (SAR). We
      find that proteins strongly interact with the polyelectrolyte film whatever the
      sign of the charge of both the multilayer and the protein. When charges of the
      multilayer and the protein are similar, one usually observes the formation of
      protein monolayers, which can become dense. We also show that when the protein
      and the multilayer become oppositely charged, the adsorbed amounts are usually
      larger and the formation of thick protein layers extending up to several times
      the largest dimension of the protein can be observed. Our results confirm that
      electrostatic interactions dominate protein/polyelectrolyte multilayer
      interactions.

PMID- 12202196
TI  - Transient amidolytic activity changes of plasmin adsorbed onto carbons.
AB  - The amidolytic activity of plasmin (Pln) that spontaneously adsorbs from
      solutions to modified-graphite (GR) and glassy carbon (GL) surfaces was studied
      in the 10-45 degrees C temperature range in the presence of a chromogenic
      substrate. Surfaces were modified with a coating of fibrinogen, either
      electrochemically oxidized or not. The effect of an additional modification via
      deposition of Langmuir-Blodgett films of behenic acid (BA-LB) onto the former
      surfaces, thus leading to either hydrophobic or hydrophilic surfaces according to
      the number of deposed layers, was examined. In all cases results showed the
      occurrence of a first order transition which strongly and transiently increases
      the surface activity of Pln. At BA-LB surfaces, the most prominent change
      compared with other coatings was a significant enhancement of the critical
      temperature Tc that characterizes the beginning of the transition. When
      fibrinogen was present in the solution, the transition was no longer observable
      up to 37 degrees C as shown by the linear kinetics exhibited by surfaces bearing
      oxidized fibrinogen.

PMID- 12202197
TI  - Assessment of techniques used in calculating cell-material interactions.
AB  - A review of the techniques used in measuring the forces of deadhesion of cells
      that have been adhering on substrate surfaces is presented. Two categories of
      techniques are described, those that utilize fluid flowing against the adhered
      cells and counting the percentage of cells that detach (global tests) and the
      manipulation of single cells in various configurations which lend themselves to
      more specific force application and provide the basis for theoretical analysis of
      the receptor-ligand mechanics.

PMID- 12202198
TI  - Biodegradable polymer networks based on oligolactide macromers: synthesis,
      properties and biomedical applications.
AB  - Novel linear and star-shaped oligolactide macromers were synthesized by ring
      opening oligomerization of L-lactide in the presence of suitable initiators (di-
      and polyols, amino acid esters) and subsequent endgroup-functionalization of the
      formed oligolactides with methacrylate moities. The obtained liquid macromers are
      valuable building blocks for the preparation of biocompatible polymer networks.
      Based on these macromers, the fabrication and the material properties including
      biodegradation behaviour of highly porous polymer network devices will be
      described. The application of these materials as resorbable scaffolds in tissue
      engineering will be discussed.

PMID- 12202199
TI  - Proceedings of Symposium G on Cell-Biosystem Material Interactions E-MRS 2001
      Spring Conference. Strasbourg, France, June 5-8, 2001.

PMID- 12202200
TI  - Emergence of influenza A H1N2 reassortant viruses in the human population during
      2001.
AB  - Influenza A H1N2 viruses, which emerged during 2001, are genetic reassortants
      between H1N1 and H3N2 subtype viruses which have cocirculated in the human
      population since 1977. They possess a H1 hemagglutinin antigenically and
      genetically similar to contemporary A/New Caledonia/20/99 (H1N1)-like viruses and
      seven genes closely related to those of recent A/Moscow/10/99 (H3N2)-like
      viruses. The viruses have spread to many regions of the world and have
      predominated over H1N1 viruses in several countries. Since half of the amino acid
      changes which accumulated in the HAs of H1N1 viruses since 1995 are in residues
      implicated in receptor binding, functional changes in the H1 HA may have
      facilitated its replacement of the H3 HA and may contribute to the future
      epidemiologic significance of these H1N2 viruses.

PMID- 12202201
TI  - Differential effects of DNA tumor virus genes on the expression profiles,
      differentiation, and morphogenetic reprogramming potential of epithelial cells.
AB  - The availability of cell lines that retain their differentiation programs is
      important for the study of differentiated cell types and the development of cell
      therapies. DNA tumor virus genes are often used to establish cell lines from
      primary culture for the analysis of cell-specific functions. To ascertain whether
      viral immortalizing or transforming genes differed in their effects on cellular
      differentiation programs, the E1A 12S (WT12S) gene of adenovirus and the large T
      antigen (LT) gene of SV40 were used to derive stable cell lines from primary
      kidney. The resultant cell types exhibited very different morphologies, growth
      and behavior patterns, differentiation states, and plasticities. Renal cells
      immortalized by LT exhibited branching tubulogenesis in response to Matrigel.
      This was in contrast to their behavior under normal culture conditions, wherein
      they were less differentiated, very nonadhesive, very rapidly growing, and
      transformed. These cells coexpressed adult epithelial (keratin) and embryonic
      mesenchymal (vimentin, osteopontin, FSP1, PAX-2, and WT1) genes. WT12S
      immortalized cells grown on or in Matrigel formed cysts or tubules, consistent
      with their expression profiles, which consisted of both epithelial and adult
      kidney markers (E-cadherin, alpha-catenin, circumferential actin filaments (CAF),
      alkaline phosphatase, aminopeptidase M, BMP7, or podocalyxin), but not
      embryonic/mesenchymal markers (PAX-2 or WT1). The WT12S-expressing cells were
      well differentiated, adhesive, slow growing, and nontransformed. Thus, cells
      expressing WT12S maintained their original differentiation status and were less
      sensitive to reprogramming, while cells expressing LT were dedifferentiated, but
      had the potential for reprogramming by exogenous factors.

PMID- 12202202
TI  - Phosphorylation of hepatitis C virus core protein by protein kinase A and protein
      kinase C.
AB  - Hepatitis C virus (HCV) core protein can form capsid-like particles and is
      believed to be the viral capsid protein. Besides its structural functions, this
      protein is also known to possess multiple regulatory functions. In this article,
      we have studied the possible phosphorylation of HCV core protein in two different
      human liver-derived cell lines Huh7 and HepG2. Our results indicated that the HCV
      core protein could be phosphorylated, albeit inefficiently, independent of its
      downstream E1 protein in these two cell lines. Two of the basal phosphorylation
      sites were identified to be serine-53 and serine-116. The phosphorylation of the
      core protein could be enhanced by the PKC activator phorbol 12-myristic 13
      acetate (PMA), and the PKA activator forskolin, and these enhancements could be
      abolished by the respective inhibitors of PKC and PKA, indicating that the core
      protein is a substrate of these two kinases. While both serine-53 and serine-116
      served as the PKC phosphorylation sites, serine-116 appeared to be the major PKA
      phosphorylation site. Further analyses using serine-to-alanine mutation to mimic
      dephosphorylation and serine-to-aspartic acid mutation to mimic phosphorylation
      revealed that the conversion of serine-116 to aspartic acid led to an enhanced
      nuclear localization of the core protein. This observation indicates that one
      function of phosphorylation may be to regulate the nuclear localization of the
      core protein.

PMID- 12202203
TI  - Golgi localization of Hantaan virus glycoproteins requires coexpression of G1 and
      G2.
AB  - The membrane glycoproteins G1 and G2 of Hantaan virus (HTNV; family Bunyaviridae)
      are encoded on the M RNA genome segment as a precursor polypeptide that is
      cotranslationally cleaved by host proteases. G1 and G2 accumulate in the Golgi
      complex in cells following either virus infection or transfection with M segment
      cDNA. However, there are conflicting reports in the literature concerning the
      Golgi targeting of separately expressed G1. To resolve these differences, a
      series of M segment and G1 coding region cDNA mutants was constructed containing
      either C-terminal or internal deletions. The intracellular localization of
      proteins expressed from these constructs was investigated by using confocal
      microscopy and double-staining immunofluorescence with G1 and G2 specific
      monoclonal antibodies and antisera specific for markers of the Golgi complex
      (GM130 and mannosidase II) and of the ER (calnexin). When expressed individually,
      G1 and G2 were retained in the ER, whereas when coexpressed from separate
      plasmids, both proteins localized to the Golgi. A construct expressing the whole
      G1 coding region and the complete signal sequence of G2 (amino acids 1-648 of the
      precursor) was found to be the minimal G1 protein competent to rescue G2 to the
      Golgi. This suggests that the G1 cytoplasmic tail including the downstream G2
      signal peptide plays an important role in Golgi localization of HTNV
      glycoproteins. None of the constructs with internal deletions in the cDNA
      expressed proteins that localized to the Golgi. Our results indicate that the
      Golgi retention signal of HTNV glycoproteins may depend on the conformation of
      oligomerized G1 and G2 complex rather than a precise primary amino acid sequence.

PMID- 12202204
TI  - Avian encephalomyelitis virus induces apoptosis via major structural protein VP3.
AB  - Avian encephalomyelitis virus (AEV) strain L(2)Z was investigated for its
      apoptotic activity in specific-pathogen-free chick embryo brain tissue. DNA
      fragmentation analysis and electron microscopy observation demonstrated that AEV
      could induce apoptosis in chick embryo brain tissues characterized by chromatin
      condensation, plasma membrane blebbing, cell shrinkage, and nucleosomal DNA
      fragmentation after 4 days postinfection. AEV structural protein genes VP1, VP2,
      and VP3 were transfected into Cos-7 and chick embryo brain (CEB) cells,
      respectively. The results showed that only VP3 protein was an apoptotic inducer,
      as demonstrated by DNA fragmentation analysis and TUNEL assay at 24 and 48 h
      posttransfection. Furthermore, expression of VP3 protein resulted in the
      activation of caspase-3-like proteases in both cells, which could be inhibited by
      a caspase-3-like protease-specific inhibitor Ac-DEVD-CHO peptide, suggesting that
      AEV VP3 protein induces apoptosis through a caspase-3-like protease pathway. In
      addition, VP3 protein localized to mitochondria in the Cos-7 and CEB cells at 24
      h posttransfection observed by confocal microscopy, indicating that mitochondria
      may play an important role in VP3-induced apoptosis. Taken together, our results
      show that AEV could induce apoptosis in chick embryo brain tissue, structural
      protein VP3 could serve as an apoptotic inducer resulting in apoptosis in cell
      culture through a caspase-3-like protease pathway, which may be related to its
      localization to mitochondria.

PMID- 12202205
TI  - Mutations in Turnip mosaic virus P3 and cylindrical inclusion proteins are
      separately required to overcome two Brassica napus resistance genes.
AB  - The Brassica napus differential line 165 is resistant to infection by Turnip
      mosaic virus (TuMV) isolates belonging to pathotypes 1 and 3. Nucleotide
      sequences of resistance-breaking mutants of pathotype 1 (UK 1), pathotype 3 (CHN
      12), and wild-type isolates have been determined. When the mutations identified
      were introduced into an infectious clone of UK 1, a single mutation in the viral
      P3 protein induced a hypersensitive (necrotic) response in inoculated leaves of
      line 165 plants. Full systemic nonnecrotic infection was only possible when
      another mutation (in the cylindrical inclusion protein) was introduced. Tests on
      segregating populations derived from line 165 indicated that the two viral genes
      were pathogenicity determinants for two different resistance genes in line 165.
      One gene responsible for an extreme form of resistance (no symptoms seen) was
      epistatic to a second responsible for the hypersensitive reaction. These results
      help to explain the relative stability of the resistance in line 165 and to
      further define the genetic basis of the TuMV pathotyping system.

PMID- 12202206
TI  - New targets for antivirals: the ribosomal A-site and the factors that interact
      with it.
AB  - Many viruses use programmed -1 ribosomal frameshifting to ensure the correct
      ratio of viral structural to enzymatic proteins. Alteration of frameshift
      efficiencies changes these ratios, in turn inhibiting viral particle assembly and
      virus propagation. Previous studies determined that anisomycin, a peptidyl
      transferase inhibitor, specifically inhibited -1 frameshifting and the ability of
      yeast cells to propagate the L-A and M(1) dsRNA viruses (J. D. Dinman, M. J. Ruiz
      Echevarria, K. Czaplinski, and S. W. Peltz, 1997, Proc. Natl. Acad. Sci. USA 94,
      6606-6611). Here we show that preussin, a pyrollidine that is structurally
      similar to anisomycin (R. E. Schwartz, J. Liesch, O. Hensens, L. Zitano, S.
      Honeycutt, G. Garrity, R. A. Fromtling, J. Onishi, and R. Monaghan, 1988. J.
      Antibiot. (Tokyo) 41, 1774--1779), also inhibits -1 programmed ribosomal
      frameshifting and virus propagation by acting at the same site or through the
      same mechanism as anisomycin. Since anisomycin is known to assert its effect at
      the ribosomal A-site, we undertook a pharmacogenetic analysis of mutants of trans
      acting eukaryotic elongation factors (eEFs) that function at this region of the
      ribosome. Among mutants of eEF1A, a correlation is observed between
      resistance/susceptibility profiles to preussin and anisomycin, and these in turn
      correlate with programmed -1 ribosomal frameshifting efficiencies and killer
      virus phenotypes. Among mutants of eEF2, the extent of resistance to preussin
      correlates with resistance to sordarin, an eEF2 inhibitor. These results suggest
      that structural features associated with the ribosomal A-site and with the trans
      acting factors that interact with it may present a new set of molecular targets
      for the rational design of antiviral compounds.

PMID- 12202207
TI  - Catalytic efficiency and phenotype of HIV-1 proteases encoding single critical
      resistance substitutions.
AB  - We have shown that a bacteriophage lambda genetic screen system may be useful in
      predicting the activity and phenotype of HIV-1 protease in the course of viral
      infection and antiretroviral therapy. This simple and rapid genetic screening
      system has been used here to characterize HIV-1 proteases encoding single primary
      resistance substitutions. Except for proteases with amino acid changes at
      positions 46 and 84, proteases containing single-resistance substitutions
      displayed a lower catalytic efficiency than the WT enzyme. Single mutants could
      be identified by their efficiency, demonstrating that modest differences in
      protease activity can be monitored with this simple assay. Overall, drug
      susceptibility could be reduced by introduction of single mutations. However,
      high-level protease inhibitor (PI) resistance was only achieved by multiple
      mutated proteases. The small but reproducible increase in resistance displayed by
      single mutants also demonstrated the ability of this genetic screen system for
      detecting minor reductions in drug susceptibility. These results show that the
      bacteriophage lambda genetic screen system used here is a useful tool in the
      analysis of specific contribution of mutations in the HIV protease-coding region
      or in specific cleavage sites that affect the process of PI resistance.

PMID- 12202208
TI  - Azathioprine inhibits vaccinia virus replication in both BSC-40 and RAG cell
      lines acting on different stages of virus cycle.
AB  - In the present study we demonstrate that azathioprine (AZA) inhibits vaccinia
      virus (VV) replication in both BSC-40 and RAG cell lines, acting on different
      stages of virus cycle. In BSC-40 cells, early protein synthesis was not
      significantly affected, but late gene expression was severely impaired. In RAG
      cells all stages of gene expression were completed during synchronous infection
      in the presence of the drug. The onset of DNA replication was not affected in RAG
      cells, but a severe inhibition was observed in BSC-40 cells. Electron microscopic
      analysis of VV-infected RAG cells treated with AZA revealed brick-shaped
      particles presenting abnormal definition of the internal structure. Purified
      virions from AZA-treated RAG cells presented several modifications of the protein
      content, a lesser amount of DNA, and a lower PFU:particle ratio. Our results
      suggest that in VV-infected RAG cells AZA interfered with virus morphogenesis,
      whereas in BSC-40 cells the replicative cycle was inhibited at the DNA
      replication stage.

PMID- 12202209
TI  - The carboxyl segment of the mumps virus V protein associates with Stat proteins
      in vitro via a tryptophan-rich motif.
AB  - Viruses of the Paramyxovirinae, similar to other viruses, have evolved specific
      proteins that interdict IFN action as part of a general strategy to counteract
      host innate immunity. In many (but not all) cases, this interdiction is
      accompanied by a lowering of the intracellular levels of the STAT proteins. Among
      rubulaviruses, there is a notable variation in how they interfere with IFN
      action. Whereas SV41, SV5, and MuV all act by lowering Stat1, hPIV2 acts by
      lowering Stat2. Here, we show that the mumps and hPIV2 V proteins both form a
      complex with several Stat proteins in a mixed-extract assay. This suggests that
      the specific degradation of these Stat proteins is not determined by complex
      formation, but presumably at some later stage of the degradation pathway. V/Stat
      complex formation requires a specific carboxyl segment of V. However, a
      previously unrecognized trp-rich motif, rather than the Zn(++)-binding cys
      cluster of this segment, appears to be required for V/Stat interaction. The C
      protein of Sendai (respiro-) virus, another P gene encoded protein, also forms a
      complex with Stat1, and prebinding of MuV V to Stat1 prevents the subsequent
      binding of SeV C. Our results suggest that rubulavirus V proteins may be related
      to both the C and the V proteins of respiroviruses.

PMID- 12202210
TI  - Effect of Ku80 depletion on the preintegrative steps of HIV-1 replication in
      human cells.
AB  - To gain new insights regarding the role of Ku, the DNA-PK DNA-binding component,
      during lentiviral DNA integration, we have investigated the HIV-1 replication in
      Ku80-depleted human cells. CEM4fx cells underexpressing the Ku80 factor were
      selected after transduction by a retroviral vector expressing the Ku80 full
      length antisense sequence. De novo infection experiment with NL4.3 HIV-1 strain
      led to the observation that the viral replication was delayed in the Ku80
      depleted cells. Early events of the replicative cycle, including nuclear import
      of the viral DNA, were not affected. In contrast, the formation of the 2-LTR
      circles was impaired, thus demonstrating the implication of Ku in HIV-1 DNA
      circularization, for the first time in human cells. Furthermore, the detection of
      integrated proviruses by an Alu-LTR-nested PCR amplification method was affected
      in cells underexpressing Ku80. These results suggest that this factor may also be
      involved in the mechanisms leading to the stable establishment of HIV-1 provirus.

PMID- 12202211
TI  - Compartmentalization of HIV-1 between breast milk and blood of HIV-infected
      mothers.
AB  - HIV-1 variants in breast milk and peripheral blood have been compared in three
      HIV-1 infected mothers. Analysis of DNA and RNA env C2-V3 sequences showed a
      differential distribution of HIV variants between the two compartments. The major
      provirus variant found in breast milk corresponds to a minor variant in the blood
      of two mothers. In the third mother, the predominant proviral variant detected in
      breast milk was not represented in the HIV-1 blood population. The major RNA
      variant in breast milk was not represented in the blood of two mothers. The
      predominant RNA variant in breast milk and blood was however the same for the
      third mother. Unexpectedly, the pattern of free virus variants in breast milk of
      three mothers did not correspond to that of the proviral form, suggesting that
      free viruses do not derive from infected cells in breast milk. The observation of
      a compartmentalization of HIV-1 between peripheral blood and breast milk
      emphasizes that postnatal transmission of HIV occurs with variants that may not
      be predicted from the analysis of circulating viral populations.

PMID- 12202212
TI  - Immunogold localization of tobravirus 2b nematode transmission helper protein
      associated with virus particles.
AB  - Transmission of the tobraviruses Tobacco rattle virus (TRV) and Pea early
      browning virus (PEBV) by trichodorid vector nematodes requires the viral coat
      protein (CP) and the 2b protein, a nonstructural protein encoded by RNA2, the
      smaller of the two viral genomic RNAs. It is hypothesized that the 2b protein
      functions by interacting with a small, flexible domain located at the C-terminus
      of the CP, forming a bridge between the virus particle and the internal surface
      of the vector nematode feeding apparatus. Antibodies specific for the 2b protein
      of PEBV or TRV did not bind to virus particles that were adsorbed to electron
      microscope grids and were not able to trap virus particles from extracts of
      infected plants. However, electron microscopy of thin sections of plants infected
      with PEBV probed with 2b-specific antibodies which were further gold-labeled
      showed that the 2b protein localizes exclusively to virus particles. Similarly,
      immunogold localization studies showed that the 2b protein of TRV isolate PaY4 is
      associated only with TRV PaY4 virus particles. When a recombinant TRV encoding
      the PaY4 2b protein and the CP from TRV isolate PpK20 was examined, the 2b
      protein could not be detected by Western blotting and in IGL experiments was not
      associated with virus particles. These results suggest that in the absence of a
      specific interaction between compatible CP and 2b proteins, the 2b protein does
      not accumulate.

PMID- 12202213
TI  - Genetic basis of attenuation of dengue virus type 4 small plaque mutants with
      restricted replication in suckling mice and in SCID mice transplanted with human
      liver cells.
AB  - Mutations that restrict replication of dengue virus have been sought for the
      generation of recombinant live-attenuated dengue virus vaccines. Dengue virus
      type 4 (DEN4) was previously grown in Vero cells in the presence of 5
      fluorouracil, and the characterization of 1248 mutagenized, Vero cell passaged
      clones identified 20 temperature-sensitive (ts) mutant viruses that were
      attenuated (att) in suckling mouse brain (J. E. Blaney, Jr., D. H. Johnson, C. Y.
      Firestone, C. T. Hanson, B. R. Murphy, and S. S. Whitehead, 2001, J. Virol.
      75(20), 9731-9740). The present investigation has extended these studies by
      identifying an additional 22 DEN4 mutant viruses which have a small plaque size
      (sp) phenotype in Vero cells and/or the liver cell line, HuH-7. Five mutant
      viruses have a sp phenotype in both Vero and HuH-7 cells, three of which are also
      ts. Seventeen mutant viruses have a sp phenotype in only HuH-7 cells, 13 of which
      are also ts. Each of the sp viruses was growth restricted in the suckling mouse
      brain, exhibiting a wide range of reduction in replication (9- to 100,000-fold).
      Complete nucleotide sequence was determined for the 22 DEN4 sp mutant viruses,
      and nucleotide substitutions were found in the 3'-untranslated region (UTR) as
      well as in all coding regions except NS4A. Identical mutations have been
      identified in multiple virus clones, suggesting that they may be involved in the
      adaptation of DEN4 virus to efficient growth in Vero cells. Six of the 22 sp 5-FU
      mutant viruses lacked coding mutations in the structural genes, and 17
      recombinant DEN4 viruses were generated which separately encoded each of the
      mutations observed in these six sp viruses. Analysis of the recombinant DEN4
      viruses defined the genetic basis of the sp, ts, and att phenotypes observed in
      the six sp viruses. Mutations in NS1, NS3, and the 3'-UTR were found to confer a
      greater than 100-fold, 10,000-fold, and 1000-fold reduction in replication of
      rDEN4 virus in SCID mice transplanted with HuH-7 cells, respectively, which
      serves as a novel small animal model for DEN4 infection.

PMID- 12202214
TI  - Mutational analysis of the replication signals in the 3'-nontranslated region of
      citrus tristeza virus.
AB  - Citrus tristeza virus (CTV), a member of the Closteroviridae, has a 19.3-kb
      messenger-sense RNA genome consisting of 12 open reading frames with
      nontranslated regions (NTR) at the 5' and 3' termini. The 273 nucleotide (nt) 3'
      NTR is highly conserved ( approximately 95%) among the sequenced CTV isolates in
      contrast to the highly diverse 5'-NTR sequences. The 3' replication signals were
      mapped to the 3' 234 nts within the NTR. This region of CTV does not contain a
      poly-A tract nor does it appear to fold as a tRNA-mimic. Instead, a computer
      predicted thermodynamically stable secondary structure comprised of 10 stem-and
      loop (SL) structures, referred to as SL1 to SL10 (5' to 3'), was common to all
      CTV isolates. This putative structure was used as a guide to examine the 3'
      requirements for replication in vivo. The resulting data suggest that a complex
      3' structure is required for those functions that provide for efficient
      replication of CTV in vivo such as minus-strand initiation, regulation of strand
      asymmetry, effective translation of the myriad of viral mRNAs, or stability of
      RNAs. Deletions into the 3'-NTR, up to 66 nts from the 5' direction and 11 nts
      from the 3' direction, deleting or disrupting putative SL1, SL2 and SL3, or SL10,
      resulted in continued replication, suggesting that these sequences are not
      essential for basal-level replication, but are required for efficient
      replication. Predicted stem loops 3 through 10 were examined by mutations
      designed to alter the primary structures while preserving the secondary
      structures. Mutations designed to disrupt the predicted stems of SL3, SL5, SL7,
      SL9, or SL10 resulted in substantially reduced levels of replication, while
      compensatory mutations resulted in partial restorations of replication,
      suggesting that these predicted secondary structures are involved in replication.
      Also, the putative loop sequences of SL5, SL6, SL7, and SL9 tolerated mutagenesis
      with continued but reduced levels of replication. In contrast, all mutations
      introduced into putative SL4, SL8, and the stem of SL6 prevented replication,
      suggesting that the primary structure of these regions make up the core of the 3'
      replication signal. The 3' triplet, CCA, was shown to be necessary for efficient
      replication, but deletion of eleven nts to expose an internal CCA resulted in
      continued replication.

PMID- 12202215
TI  - Lysine-independent ubiquitination of Epstein-Barr virus LMP2A.
AB  - Latent membrane protein 2A (LMP2A) of latent Epstein-Barr virus (EBV)
      specifically associates with HECT domain-containing Nedd4-family ubiquitin
      protein ligases (E3s). Here we demonstrate that LMP2A is specifically
      ubiquitinated by the HECT domains of AIP4 and WWP2. Deletion and site-specific
      mutation of LMP2A indicates that LMP2A is ubiquitinated at its amino-terminus and
      is not ubiquitinated on lysine residues. LMP2A and LMP1, also encoded by EBV, are
      two of only four proteins that have been identified that are ubiquitinated at the
      amino-terminus, indicating that EBV may specifically target and utilize this host
      cell protein modification.

PMID- 12202216
TI  - HIV-1 gag polyprotein rescues HLA-DR intracellular transport in a human CD4+ cell
      line.
AB  - Major histocompatibility complex class II HLA-DR molecules are plasma-membrane
      integral heterodimers, constitutively expressed in antigen-presenting cells.
      Their expression is known to be upregulated in peripheral T lymphocytes upon cell
      activation and to be constitutive in T cell lines. In H78-C10.0, a subclone of
      the human CD4+ T cell line HUT-78, the transport of MHC class II HLA-DR molecules
      is blocked, resulting in their localization within internal vesicular
      compartments rather than at the cell surface. In this article, we show that HIV
      1(HX10) infection of H78-C10.0 cells induces HLA-DR surface expression. Moreover,
      the produced infectious viruses harbor the heterodimer molecules in their
      envelopes. To define which of the viral proteins was involved in this phenomenon,
      we infected H78-C10.0 cells with recombinant vaccinia vectors containing either
      the gag-pro coding sequence or the entire env gene. Only gag expression was able
      to induce HLA-DR cell-surface localization in H78-C10.0 cells. RT-PCR analysis of
      the infected cells revealed no significant alteration in the amount of HLA
      DRalpha-specific RNA compared to untreated cells. This implies that Gag acts on
      downstream events. When the env viral gene, coding for the precursor glycoprotein
      gp160, was expressed in H78-C10.0, the Env protein targeted to the cell surface
      was poorly processed to its final mature forms gp120 and gp41. However,
      coexpression of the env and gag genes led to restoration of this phenotype.
      Although the mechanism is unknown, the data compiled in this study strongly
      suggest that the viral Gag protein can interact with the cellular trafficking
      apparatus. Moreover, in a specific cell type as H78-C10.0 this interaction can
      even reverse intracellular transport defects.

PMID- 12202217
TI  - Measles virus receptor SLAM (CD150).

PMID- 12202218
TI  - One, two, or three step: measles virus receptor dance.

PMID- 12202219
TI  - Expression of HCV structural proteins impairs IFN-mediated antiviral response.
AB  - Hepatitis C virus (HCV), especially the genotype 1, is naturally resistant to the
      antiviral effects of interferon-alpha (IFN-alpha). Expression of the whole HCV
      genome and the NS5A protein has been suggested to interfere with the antiviral
      activity of IFN-alpha. Here we have analyzed the effect of individual or various
      combinations of HCV proteins on IFN-alpha-mediated antiviral effect against
      vesicular stomatitis virus (VSV). When the structural proteins (core-E1-E2) of
      HCV genotype 1 were expressed in human osteosarcoma cells in a tetracycline
      regulated manner, partial VSV resistance to IFN-alpha was established. This was
      seen as an enhancement of both viral protein synthesis and production of
      infectious virus. Priming of core-E1-E2-expressing cells with low doses of IFN
      gamma (10 IU/ml) partially restored the antiviral activity of IFN-alpha. The core
      (high-level expression) and NS4B protein expression also showed some rescue of
      VSV replication. In this model cell system NS3A-NS4A complex and NS5A showed no
      inhibition of IFN-alpha-induced antiviral activity. Our results indicate that the
      expression of structural proteins of HCV may impair the antiviral activity of
      IFNs.

PMID- 12202220
TI  - Mutational analysis of the Sendai virus V protein: importance of the conserved
      residues for Zn binding, virus pathogenesis, and efficient RNA editing.
AB  - The V protein of Sendai virus (SeV) is nonessential for virus replication in cell
      culture but indispensable for viral pathogenicity in mice. At the C terminus of
      the V protein, there are amino acid residues conserved among the members of the
      Paramyxovinae subfamily that are clustered in three regions: region I, just
      downstream of the RNA editing site; and regions II and III, cysteine-rich zinc
      finger-like regions. In the present study, we introduced mutations into the
      conserved amino acids and generated nine mutant viruses. All of the viruses had
      impaired virus replication in mouse lungs and attenuated virulence in mice.
      Furthermore, the C-terminal polypeptides fused with glutathione-S-transferase
      with a mutation in region I, II, or III all had impaired Zn binding in a (65)Zn
      binding assay in solution. These results demonstrate that the conserved amino
      acids are important for V protein function, probably via protein conformation
      dependent on Zn binding. One mutant, SeV V-H(318)N, had inefficient RNA editing,
      indicating that the nucleotide that is a part of the codon encoding histidine at
      position 318 is conserved for the RNA editing machinery. In addition, to
      determine the function of the C-terminal extension of the V protein, which is not
      translated in recent virulent field isolates, a translational stop codon was
      introduced to generate the corresponding short V protein. The mutant virus showed
      similar virus propagation and pathogenicity, indicating that C-terminal extension
      of the V protein is not relevant to virus pathogenesis.

PMID- 12202221
TI  - Microarray analysis of gene expression during bacteriophage T4 infection.
AB  - Genomic microarrays were used to examine the complex temporal program of gene
      expression exhibited by bacteriophage T4 during the course of development. The
      microarray data confirm the existence of distinct early, middle, and late
      transcriptional classes during the bacteriophage replicative cycle. This approach
      allows assignment of previously uncharacterized genes to specific temporal
      classes. The genomic expression data verify many promoter assignments and predict
      the existence of previously unidentified promoters.

PMID- 12202222
TI  - Role of nucleotide sequences in the V3 region in efficient replication of CCR5
      utilizing human immunodeficiency virus type 1 in macrophages.
AB  - Macrophages express both CXCR4 and CCR5 coreceptors, but restrict X4 HIV-1
      replication unless the Env-V3 region, a major determinant of cell tropism, is
      exchanged with that of R5 HIV-1. As the V3 exchange concomitantly alters the
      nucleotide sequences, we introduced silent mutations in the V3 or C2 region of
      macrophage-tropic R5 JRFL without changing the amino acids. Immunoblot analysis
      confirmed that viral proteins including Env-gp120 were similarly incorporated in
      wild-type (wt) and mutant virions. The silent mutants infected CCR5-positive
      MAGIC5 cells but not CCR5-negative MAGI cells, as productively as wt viruses,
      indicating that the silent mutations did not alter coreceptor utilization. In
      contrast, two of three silent V3-mutant viruses failed to replicate efficiently
      in primary macrophages, whereas other V3- or C2-mutants and wt JRFL infected
      macrophages productively. Furthermore, synthesis of the full-length viral DNA of
      the aberrant V3-mutant was largely reduced in macrophages. These results suggest
      that V3 nucleotide sequences may be one of the postentry factors restricting HIV
      1 replication in macrophages.

PMID- 12202223
TI  - Adenovirus-microbead conjugates possess enhanced infectivity: a new strategy for
      localized gene delivery.
AB  - We have created a novel method for coupling adenoviral vectors to solid
      microbeads in a way that does not adversely affect the infectivity of the
      attached virions. This method utilizes the extremely tight interaction between
      the protein streptavidin and its ligand biotin as a means of tethering viral
      particles to microbeads. The adenovirus-microbead conjugates that were created
      functioned as fully infectious entities and possessed several functional
      advantages over free, unmodified viral particles. The adenovirus-microbead
      conjugates possessed enhanced ability to transduce target cells in culture. For
      target cells of a highly permissive nature, this increase in infectivity was
      modest. However for target cells of moderate to low permissivity, the enhancement
      of transduction efficiency was substantial. Adenoviral vectors, previously
      incapable of infecting a particular colon cancer cell line, were made fully
      infectious on the same cell line when delivered as solid-phase conjugates.
      Additionally, solid-phase adenovirus-microbead conjugates showed highly limited
      diffusion in solution, allowing for focused delivery of viral vectors only to
      cells that come into contact with the conjugates. When the solid phase to which
      the viral particles were attached had paramagnetic properties, the location of
      viral infections was tightly controllable by magnetic force through the use of
      strategically placed magnets.

PMID- 12202224
TI  - Transcriptional analysis and preliminary characterization of ORF Bm42 from Bombyx
      mori nucleopolyhedrovirus.
AB  - Clusters of closely spaced genes are frequently present in baculovirus genomes.
      We report here the detailed transcriptional mapping of one such gene cluster from
      Bombyx mori nucleopolyhedrovirus (BmNPV) comprising five ORFs, viz., Bm42, Lef
      10, VP1054, Bm44, and Bm45, which are closely spaced and transcribed in the same
      orientation. This region is homologous to ORFs 53, 53a, 54, 55, and 56,
      respectively, on the AcMNPV genome. Multiple, overlapping sets of polycistronic
      transcripts from this region, that initiate independently but terminate at a
      common 3' end, were detected following BmNPV infection. Expression of these genes
      followed a temporal pattern where the shorter transcripts initiating downstream
      appeared early, and with the progress of infection the longer transcripts
      initiated from upstream. The first ORF in this cluster, Bm42, is conserved in
      almost all baculoviruses, but has not been characterized so far. The protein was
      localized in the cytosol, predominantly near the nucleus-cytoplasm boundary in
      BmNPV-infected BmN cells. Bm42 was present in the budded virions and was not
      associated with occluded virus particles or the polyhedral matrix.

PMID- 12202225
TI  - Phylogenetic analysis of the complete genome of 18 Norwalk-like viruses.
AB  - "Norwalk-like viruses" (NLV), a member of the family Caliciviridae, are the major
      causative agents of acute gastroenteritis and are genetically divided into two
      groups, genogroup I (GI) and genogroup II (GII). We have determined the complete
      nucleotide sequences of 10 new NLV strains. Using this information together with
      eight known NLV sequences, the criteria to further classify genotypes of NLV were
      investigated. Validation of the topological error based on the bootstrap value
      and the branch length (distance) allowed us to identify two potential subgenomic
      regions suitable for the genotyping. They were the putative 3D-like RNA-dependent
      RNA polymerase (polymerase) and the capsid N-terminal/Shell domains (capsid N/S
      domain). When the distance distribution analysis was performed, the polymerase
      based classification did not separate the strains into internal clusters within
      the genogroup. Furthermore, a diversity plot analysis of the complete nucleotide
      sequences of WUG1, a NLV GI strain, and Saitama U1, a NLV GII strain, indicated
      that the genotype was different between the polymerase and capsid N/S domain,
      suggesting that these strains are the genetic recombinants. Therefore, polymerase
      is not suitable for genotyping. On the other hand, the clustering based on the
      capsid N/S domain successfully distinguished the NLV as well as the grouping
      based on the antigenicity, as determined by both antigen and antibody ELISAs with
      recombinant virus-like particles. As the nucleotide sequences of the primers for
      the capsid N/S domain are highly conserved among the NLV, the amplification of
      the unknown genotype can be easily performed. This method will facilitate global
      surveying as well as epidemiologic study on NLV.

PMID- 12202226
TI  - Interaction between TGFbeta signaling proteins and C/EBP controls basal and Tat
      mediated transcription of HIV-1 LTR in astrocytes.
AB  - Signal transduction pathways induced by cytokines can modulate the level of HIV-1
      gene transcription and replication in a variety of cells including those from the
      central nervous system. Here, we investigated the effect of TGFbeta-1 signaling
      the factors, including Smads, on transcription of the viral LTR in human
      astrocytic cells. Ectopic expression of Smad-3 increased activity of the viral
      promoter, while its partner protein, Smad-4, caused a slight decrease in viral
      gene transcription. Further, Smad-4 was able to suppress transcriptional
      activation of the LTR by Smad-3 as well as by C/EBPbeta, another activator of LTR
      transcription in these cells. Results from promoter deletion experiments
      identified the C/EBP-binding site, which is positioned between nucleotides -114
      and -102 as one of the targets for Smad-mediated regulation of the LTR. Band
      shift studies showed inhibition of C/EBP binding to its target DNA in protein
      extract from cells overexpressing Smad-3 and Smad-4. Results from GST pull-down
      assay and combined immunoprecipitation/Western blot of protein extracts from
      human astrocytes verified the association of Smad-3 and Smad-4 with C/EBPbeta,
      suggesting that interaction of C/EBPbeta with Smad-3 and Smad-4 may have a
      negative impact upon C/EBPbeta-mediated activation of the LTR. Interestingly,
      Smad-4 showed no inhibitory effect on viral gene transcription in cells
      expressing Tat protein. However, in the presence of Smad-3, expression of Smad-4
      exerted a negative effect on Tat-mediated activation of the LTR promoter. These
      observations pointed to the functional interplay between viral and cellular
      proteins in modulating LTR transcription.

PMID- 12202227
TI  - Chimeric polypeptide of thymidine kinase and thymidylate kinase of shrimp white
      spot syndrome virus: thymidine kinase activity of the recombinant protein
      expressed in a baculovirus/insect cell system.
AB  - The unique chimeric organization of the white spot syndrome virus (WSSV) tk-tmk
      gene encodes a protein which has significant homology to both cellular-type
      thymidine kinase (TK) and cellular-type thymidylate kinase (TMK), but the
      functional activity of this protein has not been demonstrated. Because TK is
      usually expressed only at very low levels in host cells, in this study, the
      coding region of WSSV tk-tmk was expressed in an insect/baculovirus expression
      system. The His-tagged recombinant WSSV TK-TMK was purified by affinity
      chromatography, and its enzyme activity was characterized by steady-state
      kinetics. The recombinant WSSV TK-TMK catalyzed the phosphorylation of thymidine
      to form thymidine monophosphate (TMP), but we found no evidence that it was able
      to catalyze the further phosphorylation of TMP to form thymidine diphosphate (or
      thymidine triphosphate). This TK activity is sensitive to feedback inhibition by
      thymidine triphosphate. In addition to thymidine, of the nine other substrates
      tested, including acyclovir, ganciclovir, and 5-(2-bromovinyl)-2'-deoxyuridine,
      only 2'-deoxyuridine and 5-bromo-2'-deoxyuridine could also serve as substrates.
      These data suggest that the enzymatic characteristics of the recombinant WSSV TK
      TMK are similar to those of the eukaryotic cytosolic TKs. We also found that TK
      activity increased as infection advanced in the integument and gills of
      experimentally infected shrimp, suggesting its functional involvement during WSSV
      infection.

PMID- 12202228
TI  - Regulation of HIV-1 transcription in activated monocyte macrophages.
AB  - DNA-binding and functional assays examined the role played by NF-IL6 in
      regulation of HIV-1 transcription in human monocyte/macrophages (U937 cells),
      stimulated with LPS+PMA. When incubated with nuclear extracts from stimulated
      cells, a region (-189/-147), containing the major NF-IL6-binding sequence and the
      USF site, interacted selectively with USF1 and USF2. Anti-C/EBPbeta reacted
      poorly with the complexes produced with the wild-type probe. In contrast, complex
      formation with NF-IL6 was clearly evident in experiments analyzing a probe
      containing an insertion in the USF site. In functional assays, increasing
      concentrations of a decoy against NF-IL6 reduced gene expression from the LTR of
      the wild-type HIV-1 variant, supporting a critical role for NF-IL6 in regulation
      of HIV-1 transcription in stimulated monocyte/macrophages. The decoy also reduced
      gene expression from a deletion construct lacking NF-IL6-binding sequences. The
      results implied that in LPS+PMA-stimulated monocyte/macrophages, the endogenous
      NF-IL6 could act via a site-independent pathway in upregulation of HIV-1
      transcription. Analysis of a short DNA segment, containing the -189/-147 region,
      suggested functional interactions of NF-IL6 and USF. In activated cells exogenous
      NF-IL6 enhanced dramatically gene expression through a short DNA segment
      containing the NF-kappaB sites, supporting functional interactions of NF-IL6 and
      NF-kappaB.

PMID- 12202229
TI  - Influenza A virus with defective M2 ion channel activity as a live vaccine.
AB  - We propose a rational approach to the design of live virus vaccines against
      influenza infection by alteration of the influenza A virus M2 protein, which is
      responsible for ion channel activity. Previously we demonstrated that a mutant
      A/WSN/33 (H1N1) influenza virus with defective M2 ion channel activity did not
      show appreciable growth defects in cell culture, although its growth was
      attenuated in mice (T. Watanabe, S. Watanabe, H. Ito, H. Kida, and Y. Kawaoka,
      2001, J. Virol. 75, 5656-5662). Here, we show that this M2 ion channel defective
      mutant virus, the M2del29-31, protected mice against challenge with lethal doses
      of influenza virus, indicating the potential of incorporating this M2 alteration
      in a live influenza vaccine as one of the attenuating mutations.

PMID- 12202230
TI  - Activation of HTLV-I transcription in the presence of Tax is independent of the
      acetylation of CREB-2 (ATF-4).
AB  - We have previously demonstrated that the bZIP transcription factor CREB-2, also
      called ATF-4, trans-activates, in association with the viral protein Tax, the
      human T-cell leukemia virus type I (HTLV-I) promoter. In this study, we have
      examined whether CREB-2 acetylation affects transcriptional activation mediated
      by Tax. We present evidence that CREB-2 is acetylated in vitro and in vivo. CREB
      2 is acetylated in two regions: the basic domain of the bZIP (from amino acid
      residue 270 to 300) and the short basic domain (from 342 to 351) located
      downstream from the bZIP. We also demonstrate that CREB-2 is acetylated by
      p300/CBP but not by p/CAF. Moreover, replacement of lysine by arginine in the
      basic domains decreases the trans-activating capacity of CREB-2. However, in the
      presence of Tax, the HTLV-I transcription remains fully activated by these CREB-2
      mutants. Although we cannot totally exclude that the mutations could also affect
      CREB-2 structure and activity independent of acetylation, our results suggest
      that activation of the viral promoter in the presence of Tax is independent of
      the CREB-2 acetylation.

PMID- 12202231
TI  - Analysis of the infectious entry pathway of human papillomavirus type 33
      pseudovirions.
AB  - Human papillomavirus type 33 (HPV-33) pseudovirus infection is a slow process
      dependent on the initial interaction with cell-surface heparan sulfate (T.
      Giroglou, L. Florin, F. Schafer, R. E. Streeck, and M. Sapp, 2001a, J. Virol. 75,
      1565-1570). We have now further dissected the initial steps of pseudovirus uptake
      using removal of cell-surface proteoglycans and selective inhibition of entry
      pathways. Treatment of cells with heparinase I, but not with phosphoinositol
      specific phospholipase C (PIPLC), prevented binding of papillomavirus-like
      particles and infection with HPV-33 pseudovirions, indicating that GPI-linked
      proteoglycans (glypicans) are not required for productive infection. The slow
      entry of pseudovirions was inhibited by cytochalasin D and nocodazole in a
      concentration-dependent manner, suggesting actin polymerization and intact
      microtubuli be required. Inhibitors of the caveolae-mediated uptake did not
      significantly affect pseudoinfection. Interestingly, pseudoinfection was blocked
      by selective inhibitors of endosomal acidification up to 12 h postinfection.
      Together, our results suggest that binding of HPV pseudovirions to heparan
      sulfate proteoglycans, most likely syndecans, is followed by delayed
      internalization via the endosomal pathway.

PMID- 12202232
TI  - The hepatitis B virus X protein binds to and activates the NH(2)-terminal trans
      activation domain of nuclear factor of activated T cells-1.
AB  - We have previously reported that the hepatitis B virus X protein (HBx) activates
      nuclear factor of activated T cells (NF-AT), a key regulator of the immune
      system, by a calcium/calcineurin-dependent pathway, involving dephosphorylation
      and nuclear translocation of this transcription factor. In addition, we showed
      that HBx synergizes with potent calcium-mobilizing stimuli to activate NF-AT
      dependent transcription, suggesting that additional mechanisms might also be
      operative in the activation of NF-AT by HBx. Here we demonstrate that HBx
      activates the NH(2)-terminal transcription activation domain (TAD) of NF-AT1 by a
      mechanism involving protein-protein interaction. Targeting of HBx to the nucleus
      did not affect its ability to induce the transcriptional activity of NF-AT1. In
      contrast, mutations of HBx affecting its functional interaction with general
      transcription factors abrogated the HBx-induced activity of NF-AT1. Together
      these results indicate that HBx may exert its function by acting as a nuclear
      coactivator of NF-AT1.

PMID- 12202233
TI  - Transcription mapping and expression patterns of genes in the major immediate
      early region of Kaposi's sarcoma-associated herpesvirus.
AB  - Viral immediate-early (IE) genes are the first class of viral genes expressed
      during primary infection or reactivation from latency. They usually encode
      regulatory proteins that play crucial roles in viral life cycle. In a previous
      study, four regions in the KSHV genome were found to be actively transcribed in
      the immediate-early stage of viral reactivation in primary effusion lymphoma
      cells. Three immediate-early transcripts were characterized in these regions, as
      follows: mRNAs for ORF50 (KIE-1), ORF-45 (KIE-2), and ORF K4.2 (KIE-3) (F. X.
      Zhu, T. Cusano, and Y. Yuan, 1999, J. Virol. 73, 5556-5567). In the present
      study, we further analyzed the expression of genes in these IE regions in BC-1
      and BCBL-1 cells. One of the immediate-early regions (KIE-1) that encompasses
      ORF50 and other genes was intensively studied to establish a detailed
      transcription map and expression patterns of genes in this region. This study led
      to identification of several novel IE transcripts in this region. They include a
      2.6-kb mRNA which encodes ORF48/ORF29b, a family of transcripts that are
      complementary to ORF50 mRNA and a novel K8 IE mRNA of 1.5 kb. Together with the
      IE mRNA for ORF50 which was identified previously, four immediate-early genes
      have been mapped to KIE-1 region. Therefore, we would designate KIE-1 the major
      immediate-early region of KSHV. In addition, we showed that transcription of K8
      gene is controlled by two promoters, yielding two transcripts, an immediate-early
      mRNA of 1.5 kb and a delayed-early mRNA of 1.3 kb.

PMID- 12202234
TI  - Restriction landmark genomic scanning for DNA methylation in cancer: past,
      present, and future applications.
AB  - The field of molecular biology was revolutionized by the advent of gel
      electrophoresis. Restriction landmark genomic scanning (RLGS) is a type of two
      dimensional electrophoresis employed in the genome-wide assessment of genomic
      alterations. RLGS has been used to study genetic and epigenetic changes in normal
      tissues, primary tumors, cancer cell lines, and various organisms such as mice,
      rats, hamsters, bacteria, and plants. An RLGS profile displays over 2000
      radiolabeled restriction landmark sites in a single assay. When conducted with
      methylation-sensitive restriction enzymes whose sites are preferentially located
      in CpG island regulatory regions, RLGS becomes a very versatile tool for the
      investigation of both normal and aberrant methylation patterns. Early studies
      performed on tumor DNA were mainly descriptive in nature, essentially a catalogue
      of loci that were changed to varying degrees in different tumor types. Over time,
      as investigators have become more proficient with RLGS and have undertaken high
      throughput studies, the need for efficient cloning, imaging, and analysis systems
      has become paramount. Current studies focus on identifying specific genes and
      pathways involved in deregulated methylation in cancer. As such, RLGS analysis of
      tumor samples has made tremendous contributions to our understanding of the role
      of DNA methylation in cancer. Future directions will take advantage of the
      abundant genomic sequence data available to link all of the RLGS loci to genes
      and create biologically relevant methylation profiles of cancer. This review
      discusses practical considerations of using RLGS as a genome scanning tool and
      the past, present, and future applications in cancer biology.

PMID- 12202235
TI  - Improved initial yields in C-terminal sequence analysis by thiohydantoin
      chemistry using purified diphenylphosphoryl isothiocyanate: NMR evidence for a
      reaction intermediate in the coupling reaction.
AB  - A thiohydantoin method for C-terminal sequence analysis of proteins on Zitex
      membranes involves derivatization of the free alpha-carboxyl group with
      diphenylphosphoryl isothiocyanate (DPPITC) plus treatment with pyridine to form a
      peptidylthiohydantoin derivative, cleavage of the thiohydantoin (TH) amino acid
      from the protein with potassium trimethylsilanolate, and identification of the
      released TH-amino acid by online reversed-phase HPLC. This automated chemistry,
      which was adapted to the Hewlett-Packard G 1009A sequencer, has been shown to
      identify two or three cycles on a wide variety of proteins, but suffers from low
      initial yields and instability of the DPPITC reagent. We report here an improved
      method for synthesis and purification of DPPITC. With this procedure the DPPITC
      reagent is a clear liquid that is stable at room temperature under vacuum for
      more than 9 months or for more than 24 months as a 1.0M solution in benzene at 
      20 degrees C. Using the purified reagent we were able to more than double the
      initial yield (from 30.7 to 72.4%) of TH-amino acid from a test protein and
      substantially decrease sequencer background. Examination of the reaction between
      DPPITC and the carboxylate of model N-terminally protected dipeptides with 31P
      NMR provides spectroscopic evidence for a postulated intermediate formed between
      the DPPITC and the peptide carboxylate. The reaction intermediate provides new
      insight into the coupling mechanism.

PMID- 12202236
TI  - Spectroscopic determination of protein concentrations from proteinase K digests.
AB  - A method to determine protein concentrations and absorptivities based on
      absorbance measurements of proteinase K digests has been developed. Molar
      absorptivities of proteinase K digests at 56 degrees C can be predicted by using
      the following equation: epsilon (M)(280)=5318 x (No.of Trp) + 1227 x (No.of Tyr)
      + 133 x (No.of Cys-Cys). Protein concentration in the digest can be determined by
      dividing the corrected digest solution absorbance by the calculated
      epsilon(M)(280). The absorptivity of a native protein can then be calculated by
      dividing the absorbance of the intact protein solution by the concentration value
      obtained for the digest solution. Precision of the experimental data is within +/
      3%, and the error of the method does not exceed 4.5%. The accuracy of
      determination does not depend on the size of the protein, Trp/Tyr ratio, presence
      or absence of certain chromophores, or other structural factors. The method
      requires amounts of protein routinely used for absorbance measurements.

PMID- 12202237
TI  - A mass spectrometry method for measuring 15N incorporation into pheophytin.
AB  - The 15N content of pheophytin, the magnesium-free derivative of chlorophyll, can
      be measured with great accuracy and precision using positive-ion atmospheric
      pressure ionization electrospray mass spectroscopy following a simple solvent
      extraction of small amounts of plant tissue. The molecular weight of pheophytin
      prepared from Chlamydomonas reinhardtii grown in different ratios of 14N/15N
      showed linear regression with the isotopic input, with a precision of 0.5-1%.
      Using an isotope dilution strategy, we have shown that nitrogen fixation can
      contribute substantial 14N to pheophytin isolated from Medicago truncatula plants
      grown in symbiosis with Sinorhizobium meliloti. The assay is sensitive, precise,
      rapid, simple, and robust. These features suggest that it could become an
      important tool for measuring the contribution of symbiotic and associative
      nitrogen fixation to plant metabolism.

PMID- 12202238
TI  - Studies of reversible inhibition, irreversible inhibition, and activation of
      alkaline phosphatase by capillary electrophoresis.
AB  - Reversible inhibition, irreversible inhibition, and activation of calf intestinal
      alkaline phosphatase (EC 3.1.3.1) have been studied by capillary electrophoresis.
      The capillary electrophoretic enzyme-inhibitor assays were based on
      electrophoretic mixing of inhibitor and enzyme zones in a substrate-filled
      capillary. Enzyme inhibition was indicated by a decrease in product formation
      detected in the capillary by laser-induced fluorescence. Reversible enzyme
      inhibitors could be quantified by Michaelis-Menten treatment of the
      electrophoretic data. Reversible, competitive inhibition of alkaline phosphatase
      by sodium vanadate and sodium arsenate has been examined, and reversible,
      noncompetitive inhibition by theophylline has been studied. The K(i) values
      determined for these reversible inhibitors using capillary electrophoresis are
      within the range of values reported in the literature for the same enzyme
      inhibitor combinations. Irreversible inhibition of alkaline phosphatase by EDTA
      at concentrations of 1.0mM and above has been observed. Activation of alkaline
      phosphatase has also been observed for EDTA at concentrations from 20 to 400
      microM.

PMID- 12202239
TI  - Biosensor detection of triplex formation by modified oligonucleotides.
AB  - Due to the instability of DNA oligonucleotides in biological solutions, antisense
      or antigene therapies aimed at modulation of specific gene expression will most
      likely require the use of oligonucleotides with modified backbones. Here, we
      examine the use of a surface plasmon resonance biosensor (BIAcore) to compare
      triplex-directed binding of modified oligonucleotides targeted to a region of the
      murine c-myc promoter. We describe optimization of experimental conditions to
      minimize nonspecific interactions between the oligonucleotides and the sensor
      chip surface, and the limitations imposed by certain backbones and sequence
      types. The abilities of pyrimidine oligonucleotides with various modified
      backbones to form specific triple helices with an immobilized hairpin duplex were
      readily determined using the biosensor. Modification of the third-strand
      oligonucleotide with RNA or 2(')-O-methyl RNA was found to enhance triplex
      formation, whereas phosphorothioate or phosphotriester substitutions abrogated
      it. A comparison of these results to DNase I footprinting experiments using the
      same oligonucleotides showed complete agreement between the two sets of data.

PMID- 12202240
TI  - Development of a rapid and convenient method to purify mucins and determine their
      in vivo synthesis rate in rats.
AB  - The intestinal mucoprotein synthesis rate was measured in vivo for the first
      time. For this, a rapid, reproducible, and convenient method to purify
      mucoproteins from large numbers of intestinal samples at the same time was
      developed. The method takes advantage of both the high mucin resistance to
      protease activities due to their extensive glycosylations and the high mucin
      molecular size. Intestinal homogenates were partially digested with Flavourzyme.
      Nonprotected proteins partially degraded were easily separated from mucoproteins
      by small gel filtration chromatography using Sepharose CL-4B. Electrophoretically
      pure mucins were obtained. Their amino acid composition was typical of purified
      intestinal epithelial mucins. The mucoprotein synthesis rate was determined in
      vivo in rats using the flooding dose method with the stable isotope L-[1
      13C]valine. Free L-[1-13C]valine enrichments in the intracellular pool were
      determined by GC-MS. L-[1-13C]valine enrichments into purified mucoproteins or
      intestinal mucosal proteins were measured by gas chromatography-combustion
      isotope ratio mass spectrometry. In rats, we found that the gut mucosa protein
      synthesis rate (%/day) decreased regularly from duodenum (122%/day) to colon
      (43%/day). In contrast, mucoprotein fractional synthesis rates were in the same
      range along the digestive tract, between 112%/day (colon) and 138%/day (ileum).

PMID- 12202241
TI  - Site-specific biosynthetic incorporation of a fluorescent tag into proteins via
      cysteine-tRNA(Cys).
AB  - Site-specific incorporation of biophysical probes into proteins during
      translation can permit structure/function studies on selected proteins in
      heterogeneous environments. We report here a procedure for incorporating a
      fluorescent tag into proteins via Escherichia coli Cys-tRNA(Cys) during in vitro
      protein synthesis. Naturally occurring Cys-tRNA(Cys) is an attractive vehicle for
      fluorophore incorporation since it can be readily prepared in quantity and
      reacted with commercially available fluorophores. Moreover, proteins can often be
      constructed with a single Cys so that fluorophore incorporation results in a tag
      at a unique site.

PMID- 12202242
TI  - Biosensor analysis of dynamics of interleukin 5 receptor subunit beta(c)
      interaction with IL5:IL5R(alpha) complexes.
AB  - To gain insight into IL5 receptor subunit recruitment mechanism, and in
      particular the experimentally elusive pathway for assembly of signaling subunit
      beta(c), we constructed a soluble beta(c) ectodomain (s(beta)(c)) and developed
      an optical biosensor assay to measure its binding kinetics. Functionally active
      s(beta)(c) was anchored via a C-terminal His tag to immobilized anti-His
      monoclonal antibodies on the sensor surface. Using this surface, we quantitated
      for the first time direct binding of s(beta)(c) to IL5R(alpha) complexed to
      either wild-type or single-chain IL5. Binding was much weaker if at all with
      either R(alpha) or IL5 alone. Kinetic evaluation revealed a moderate affinity
      (0.2-1 microM) and relatively fast off rate for the s(beta)(c) interaction with
      IL5:R(alpha) complexes. The data support a model in which beta(c) recruitment
      occurs with preformed IL5:R(alpha) complex. Dissociation kinetics analysis
      suggests that the IL5-alpha-beta(c) complex is relatively short-lived. Overall,
      this study solidifies a model of sequential recruitment of receptor subunits by
      IL5, provides a novel biosensor binding assay of beta(c) recruitment dynamics,
      and sets the stage for more advanced characterization of the roles of structural
      elements within R(alpha), beta(c), and cytokines of the IL5/IL3/GM-CSF family in
      receptor recruitment and activation.

PMID- 12202243
TI  - A continuous fluorescence assay for sulfhydryl oxidase.
AB  - Flavin-dependent sulfhydryl oxidases represent a newly discovered family of
      proteins with a range of cellular locations and putative roles. The avian and
      mammalian proteins can catalyze the direct oxidation of protein cysteine residues
      to disulfides with the reduction of dioxygen to hydrogen peroxide. Although
      thiols interfere with the peroxidase-mediated quantitation of hydrogen peroxide,
      a very sensitive, continuous fluorescence assay of the sulfhydryl oxidases can be
      devised with careful selection of thiol substrate concentration and fluorogen.
      Purified avian enzyme (or crude chicken egg white) was used for these
      experiments. Homovanillic acid was found to be a suitable fluorogen in the
      presence of 300 microM thiols from either dithiothreitol or reduced ribonuclease
      A. High concentrations of horseradish peroxidase minimized the effects of
      contaminating catalase in biological samples. Using fluorescence microcells, the
      assay could detect 15fmol of avian sulfhydryl oxidase and the rates were linearly
      dependent on enzyme concentration up to 6nM. Aspects of the interaction among
      thiols, homovanillic acid, and peroxidase are discussed which limit the
      sensitivity of the assay and require that care is exercised in the application of
      this new procedure. Finally, the assay is used to show that there is sulfhydryl
      oxidase activity in a number of secretory fluids including human tears.

PMID- 12202244
TI  - An efficient assay for dolichyl phosphate-mannose: protein O-mannosyltransferase.
AB  - A novel method for quantifying the reaction product from dolichyl phosphoryl
      mannose:polypeptide mannosyltransferase (protein mannosyl transferase; PMT), was
      developed. The assay quantifies the amount of radioactivity incorporated into the
      acceptor peptide YNPTSV from dolichyl phosphoryl [3H]mannose (Dol-P-Man). A novel
      delivery system, large unilamellar vesicles (LUV), composed of 1-palmitoyl-2
      oleoyl-sn-glycero-3-phosphocholine (POPC), is used to keep the poorly soluble
      donor substrate, Dol-P-Man, in solution. The use of LUV allows generation of
      truly reproducible data and, as an additional benefit, also results in a more
      than 10 times increase in transfer efficiency. In contrast to the solvent
      extraction procedures commonly used in previously described PMT assays, the assay
      reaction product is separated from the radioactive donor substrate on C(18)
      cartridges. The use of C(18) cartridges allows generation of reproducible data
      with a low, consistent background and also produces a significant reduction in
      the time and labor needed for the product workup. In a reaction mixture
      consisting of 100 microg POPC LUV, 9 x 10(5)cpm (approximately 15 pmol) Dol-P
      Man, 100 nmol YNPTSV, and aproximately 4 microg of crude yeast microsomal
      extract, time-dependent formation of glycosylated product obeys Michaelis-Menten
      type kinetics throughout the course of the reaction-until exhaustion of the donor
      substrate. The linear initial rates of the reaction allowed calculation of an
      apparent K(m) of 1mM, for the acceptor peptide YNPTSV. Variations in detergent
      concentration in the assay influence transfer efficiency, possibly through
      interference with the LUV-based donor substrate delivery system. Hence detergent
      concentrations should be kept constant.

PMID- 12202245
TI  - Development of a scintiplate assay for recombinant human alpha(2B)-adrenergic
      receptor.
AB  - A high-throughput solid-phase platform for ligand-binding assays using microtiter
      plates (Scintiplates) has been developed using the scintillation proximity assay
      principle. The system has been developed using human alpha(2B)-adrenergic
      receptor (alpha(2B)-AR) expressed from Semliki Forest virus vectors in CHO cells.
      Alpha(2B)-AR bind natural (adrenaline and noradrenaline) and synthetic ligands
      with different affinities to mediate a variety of physiological and
      pharmacological responses. Antagonist radioligands were used for the binding
      experiments, and the values obtained for the binding constants with the
      Scintiplate system are in good agreement with those obtained by the traditional
      filter-binding assay system. The Scintiplate assay offers the advantages of a
      high-throughput format over the filter-binding assay and is amenable for
      screening many compounds rapidly for generation of leads.

PMID- 12202246
TI  - Quantitative analysis of c-myc-tagged protein in crude cell extracts using
      fluorescence polarization.
AB  - A fluorescence polarization (FP) assay was developed to determine the
      concentration of a c-myc-tagged recombinant protein in a crude cell extract. The
      basis of the assay was a competition between a c-myc-tagged protein and a
      fluorescein-labeled c-myc peptide for a c-myc antibody Fab. Fluorescein-labeled c
      myc peptide produced a high-fluorescence polarization signal upon binding to the
      c-myc antibody, which can be inhibited in the presence of a c-myc-tagged protein.
      Quantitation of a c-myc-tagged protein was realized by measuring the decrease in
      fluorescence polarization. The observed IC(50) values in the competition FP assay
      were similar among all monomeric c-myc-tagged proteins tested, indicating that
      the interaction of the c-myc tag with the antibody was independent of the fusion
      protein sequence. The c-myc-tagged protein concentrations measured by FP were
      found to correlate well with values derived from a spike experiment and with
      values obtained by quantitative immunoblot. This assay was not perturbed by the
      presence of crude cell lysate, dithiothreitol or detergents, and worked with both
      native and denatured samples from several expression systems, including
      Escherichia coli, Pichia, insect cells, and mammalian cells. The assay under the
      current condition can detect as low as 0.05% expression level of c-myc-tagged
      protein with regards to total proteins, depending on the expression system. This
      assay is both quantitative and rapid (less than 15min) and is therefore suitable
      for the optimization of recombinant protein expression conditions as well as for
      the monitoring of protein purification procedures.

PMID- 12202247
TI  - Enhanced protein recovery after electrotransfer using square wave alternating
      voltage.
AB  - Protein identification is becoming a complement to the available fully sequenced
      genomes. To meet the challenge, newly developed techniques for high throughput
      protein identification using matrix-assisted laser desorption/ionisation mass
      spectrometry (MALDI-MS) and peptide mass fingerprint are needed. Two years ago, a
      parallel protein digestion process was proposed. It provided a collecting
      polyvinylidene difluoride (PVDF) membrane able to be scanned by MALDI. Acquired
      data were used to recreate a virtual multidimensional image. Voltage used during
      this protein electroblotting technique was an unusual square wave alternative
      voltage (SWAV). The goal of the current study is to evaluate quantitatively the
      efficiency of the SWAV compared with a classical electroblot process on intact
      proteins. The effect of the pulsed electric field and the buffer composition were
      compared to a standard continuous transblotting process defined as the gold
      standard. Combination of the pulsed asymmetric electric field with 3
      (cyclohexylamino)-1-propane-sulfonique acid (CAPS) buffers showed an average 65%
      increase of protein recovery. Moreover, a strongest effect is observed for high
      M(r) proteins. In conclusion, the present study highlighted a positive influence
      of the "shaking" effect of the asymmetric alternative voltage on gel protein
      extraction.

PMID- 12202248
TI  - mRNA-specific reverse transcription-polymerase chain reaction from human tissue
      extracts.
AB  - Reverse transcription-polymerase chain reaction (RT-PCR) has become the method of
      choice for detection of mRNA transcripts, including those of low abundance
      obtained from small precious samples of human tissue. A major confounding problem
      for standard reverse-transcription-priming strategies is the presence of
      contaminating genomic DNA (gDNA) carried over from the original "RNA" extract
      into the RT and PCR steps. The contaminating gDNA contains a processed pseudogene
      sequence-which lacks introns but contains a poly(A) tail-for commonly studied
      internal reference genes beta-actin and GAPDH, and target genes GSTM1, GSTP1, and
      others. These pseudogene sequences therefore confound standard-design "RNA
      specific" PCR primer pairs which rely, for cDNA versus gDNA specificity, on the
      pair-spanning introns, or one of the individual primer oligos spanning an
      exon/exon splice site, because these features are lacking in processed pseudogene
      sequences. The result is false RT-PCR positives for these "housekeeper" genes in
      total RNA extracts; the gDNA processed pseudogene is mistaken for mRNA gene
      transcript. A universal RT primer has been designed that targets the poly(A) tail
      of mRNA and adds a unique tag sequence not otherwise existing in the human
      genome. Genomic DNA does not incorporate this RT-inserted unique tag. PCR is then
      performed using a transcript-specific forward primer and a reverse primer that is
      identical to the unique tag incorporated at RT. Only cDNA made with this RT
      primer is compatible with this reverse PCR primer, thus eliminating confounding
      signal from contaminating gDNA. This method performs RNA-specific qualitative and
      quantitative evaluation of gene expression, while preserving the sensitivity of
      standard RT-PCR techniques. Applications to low-copy transcripts in human samples
      are demonstrated.

PMID- 12202249
TI  - Spectrophotometric determination of folic acid in pharmaceutical preparations by
      coupling reactions with iminodibenzyl or 3-aminophenol or sodium molybdate
      pyrocatechol.
AB  - Novel coupling reagents are used for the simple and sensitive spectrophotometric
      determination of folic acid either in pure form or in its pharmaceutical
      preparations. The methods are based on the probable diazotization of the p
      aminobenzoylglutamic acid obtained after reductive clevage of folic acid,
      followed by either coupling with iminodibenzyl to give a violet product with
      lambda(max) of 580nm or coupling with 3-aminophenol to produce an orange yellow
      colored product with lambda(max) of 460nm. Sodium molybdate and pyrocatechol are
      used in the third method and the pale red-colored product formed has a
      lambda(max) of 490nm. The methods are highly reproducible and have been applied
      to the determination of folic acid in tablets and the results compare favorably
      with the official method. Common excipients used as additives in pharmaceutical
      preparations do not interfere in the proposed methods.

PMID- 12202250
TI  - Fluorescent assay for polymerization of purified bacterial FtsZ cell-division
      protein.
AB  - Septum formation in Escherichia coli is a complex cascade of interactions among
      cell-division proteins. The tubulin-like FtsZ division protein localizes to the
      division site and serves a cytoskeletal role during septum formation. A novel
      fluorescent-based 96-well format filter assay has been developed to measure the
      polymerization of FtsZ. A mixture of monomers and aggregates (38 to approximately
      200 KDa in range) of purified wild-type FtsZ and a fluorescently tagged
      derivative of FtsZ protein in stoichiometric ratio passes through a 0.2-microm
      filter membrane, while polymerized FtsZ is retained on the filter. Addition of
      the SulA protein to the assay leads to rapid disassembly of existing FtsZ
      polymers, demonstrating its natural regulatory effect on FtsZ under the assay
      conditions. This assay is sensitive (requiring 2 microM FtsZ or less) and
      facilitates high-throughput screening of factors affecting FtsZ polymerization.

PMID- 12202251
TI  - A 96-well dot-blot assay for carbohydrate sulfotransferases.
AB  - Here we describe an efficient dot-blot assay for high-throughput screening of two
      enzymes, heparan sulfate N-deacetylase/N-sulfotransferase (NDST-1) and high
      endothelial cell GlcNAc-6-sulfotransferase (HEC-GlcNAc-6-ST). The assay proceeds
      by transfer of 35S-labeled sulfate from [35S]-3(')-phosphoadenosine-5(')
      phosphosulfate (PAPS) to the free amino groups of de-N-sulfated heparin (NDST-1),
      or the 6-hydroxyl groups of N-acetylglucosamine residues linked to a
      polyacrylamide scaffold (HEC-GlcNAc-6-ST). The 35S-labeled products are then
      captured on an appropriate membrane, taking advantage of their polymeric
      architecture. In one step, 35S-labeled by-products are then eluted from the
      membrane, leaving spatially separated 35S-labeled product "dots" for subsequent
      quantification. This assay allows for direct product detection on the membrane,
      obviating excessive washing and elution steps endemic to other assays. The assay
      was validated by measuring K(M) values for PAPS and K(I) values for PAP, the
      product of sulfuryl transfer. The assay method should be useful for inhibitor
      screens for both enzymes. In addition, the general assay architecture should be
      readily applicable to high-throughput screens of other carbohydrate
      sulfotransferases.

PMID- 12202252
TI  - Detection of serum proteins by native polyacrylamide gel electrophoresis using
      Blue Sepharose CL-6B-containing stacking gels.
AB  - Analysis of serum proteins by native polyacrylamide gel electrophoresis is
      difficult because albumin is abundant in serum and interferes with the resolution
      of other proteins, especially alpha-antitrypsin which has mobility that is very
      similar to that of albumin. We present here a method in which serum proteins are
      separated by polyacrylamide gel electrophoresis using stacking gels containing
      Blue Sepharose CL-6B, which has a high affinity for albumin, lipoproteins,
      kinases, and pyridine-nucleotide-dependent oxidoreductases. During
      electrophoresis, proteins that bind to Blue Sepharose CL-6B stay in the stacking
      gel and do not migrate into the separating gel. As a consequence, certain
      proteins, including alpha(1)-antitrypsin, can be detected as clear bands. This
      method overcomes the requirement for fractionation of serum samples prior to
      electrophoresis to remove albumin and allows the simultaneous analysis of many
      samples.

PMID- 12202253
TI  - Variable expression of some "housekeeping" genes during human keratinocyte
      differentiation.
AB  - We investigated the expression levels of four cellular "housekeeping" genes
      during epithelial differentiation. Differentiation is a dynamic process and
      various cellular RNAs have been targeted for use as internal controls during
      differentiation of human keratinocytes, but the consistent expression of such
      standards has not been previously validated. We used the organotypic (raft)
      culture system to grow stratified and differentiated epithelium in vitro. We
      compared cellular RNAs from epithelial tissues of both normal human keratinocytes
      and keratinocytes whose differentiation scheme is altered by the replication of
      human papillomavirus. Using ribonuclease protection assays to quantify RNA
      expression levels, we found that beta-actin and glyceraldehyde-3-phosphate
      dehydrogenase levels fluctuated during epithelial differentiation, whereas
      cyclophilin RNA and 28S-ribosomal RNA were the most consistently expressed during
      epithelial differentiation. These stably expressed cellular RNAs can be targeted
      as controls to permit quantitative expression analyses of cellular and pathogen
      RNAs during epithelial differentiation under various experimental conditions.

PMID- 12202254
TI  - Double bond localization in minor homoallylic fatty acid methyl esters using
      acetonitrile chemical ionization tandem mass spectrometry.
AB  - Double bond position in natural fatty acids is critical to biochemical
      properties, however, common instrument-based methods cannot locate double bonds
      in fatty acid methyl esters (FAME), the predominant analysis form of fatty acids.
      A recently described mass spectrometry (MS) method for locating double bonds in
      FAME is reported here for the analysis of minor (<1%) components of real FAME
      mixtures derived from three natural sources; golden algae (Schizochytrium sp.),
      primate brain white matter, and transgenic mouse liver. Acetonitrile chemical
      ionization tandem MS was used to determine double bond positions in 39 FAME, most
      at concentrations well below 1% of all fatty acid methyl esters. FAME identified
      in golden algae are 14:1n-6, 14:3n-3, 16:1n-7, 16:2n-6, 16:3n-6, 16:3n-3, 16:4n
      3, 18:2n-7, 18:3n-7, 18:3n-8, 18:4n-3, 18:4n-5, 20:3n-7, 20:4n-3, 20:4n-5, 20:4n
      7, 20:5n-3, and 22:4n-9. Additional FAME identified in primate brain white matter
      are 20:1n-7, 20:1n-9, 20:2n-7, 20:2n-9, 22:1n-7, 22:1n-9, 22:1n-13, 22:2n-6,
      22:2n-7, 22:2n-9, 22:3n-6, 22:3n-7, 22:3n-9, 22:4n-6, 24:1n-7, 24:1n-9, and 24:4n
      6. Additional FAME identified in mouse liver are 26:5n-6, 26:6n-3, 28:5n-6, and
      28:6n-3. The primate brain 22:3n-7 and algae 18:4n-5 are novel fatty acids. These
      results demonstrate the usefulness of the technique for analysis of real samples.
      Tables are presented to aid in interpretation of acetonitrile CIMS/MS spectra.

PMID- 12202255
TI  - Novel tools for the study of class I alpha-mannosidases: a chromogenic substrate
      and a substrate-analog inhibitor.
AB  - The use of chromogenic substrates for evaluation of class I alpha-mannosidase is
      described. 2('),4(')-Dinitrophenyl-alpha-D-mannopyranoside allows rapid and
      sensitive assays of enzymatic activities, e.g., of heterologously expressed alpha
      1,2-mannosidase from Trichoderma reesei. Interaction constants of several ligands
      with alpha-mannosidases from class I and II could also be determined.
      Furthermore, novel types of inhibitors derived from D-lyxose are presented.
      Methyl-alpha-D-lyxopyranosyl-(1(')-->2)-alpha-D-mannopyranoside is a potent
      inhibitor of the alpha-1,2-mannosidase from T. reesei (K(i)=600 microM) and since
      it probably spans subsites -1/+1, this disaccharide could be valuable in
      crystallographic studies of class I alpha-mannosidases.

PMID- 12202256
TI  - On-column tris(2-carboxyethyl)phosphine reduction and IC5-maleimide labeling
      during purification of a RpoC fragment on a nickel-nitrilotriacetic acid Column.
AB  - Fluorescence labeling of proteins has become increasingly important since
      fluorescent techniques like FRET and fluorescence polarization are now commonly
      used in protein binding studies, proteomics, and for high-throughput screening in
      drug discovery. In our efforts to study the binding of the beta(')-subunit from
      Escherichia coli RNA polymerase (RNAP) to sigma70, we synthesized a fluorescent
      labeled beta(')-fragment (residues 100-309) in a very convenient way, that could
      be used as a general protocol for hexahistidine-tagged proteins. By performing
      all the following steps, purification, reduction, derivatization with IC5
      maleimide, and free dye removal while the protein was bound to the column, we
      were able to reduce the procedure time significantly and at the same time achieve
      better labeling efficiency and quality. The beta(')-fragment with a N-terminal
      His(6)-tag was purified from inclusion bodies and could be refolded prior to or
      after binding to a Ni-NTA affinity column. Reduction prior to labeling was
      achieved with TCEP that does not interfere with Ni-NTA chemistry. The labeled
      beta(')-fragment was tested with sigma70 that was labeled with an europium-based
      fluorophore for binding in a electrophoretic mobility-shift assay. The sigma-to
      core protein interaction in bacterial RNA polymerase offers a potentially
      specific target for drug discovery, since it is highly conserved among the
      eubacteria, but differs significantly from eukaryotes.

PMID- 12202257
TI  - Nonheme iron determination.

PMID- 12202258
TI  - In vivo analysis of intracellular amino acid labelings by GC/MS.

PMID- 12202259
TI  - A novel simple method for the investigation of drug binding to the K(ATP) channel
      sulfonylurea receptor.

PMID- 12202260
TI  - Nonisotopic cytosine extension assay: a highly sensitive method to evaluate CpG
      island methylation in the whole genome.

PMID- 12202261
TI  - Real-time dual zymographic analysis of matrix metalloproteinases using
      fluorescein-isothiocyante-labeled gelatin and Texas-red-labeled casein.

PMID- 12202262
TI  - Peptide mass fingerprinting from wet and dry two-dimensional gels and its
      application in proteomics.

PMID- 12202263
TI  - In pursuit of the pathogenesis and pathophysiology of schizophrenia: where do we
      stand?

PMID- 12202264
TI  - Atypical depression: a reappraisal.
AB  - OBJECTIVE: The study evaluated the DSM-IV definition of the atypical features
      specifier for a major depressive episode in major depressive disorder. METHOD:
      Nonpsychotic patients with major depressive disorder were assessed to determine
      if the DSM-IV model and decision rules for the atypical features specifier for a
      major depressive episode could be supported. RESULTS: The five clinical features
      of the DSM-IV atypical features specifier for a major depressive episode showed
      weak internal consistency, and the mandatory criterion A feature of mood
      reactivity did not show specificity in relation to any of the four criterion B
      accessory symptoms. The more severe the depression, the less likely the patient
      was to report criterion A and hence to meet criteria for the atypical features
      specifier. Remodeling the five features favored the personality style descriptor
      of interpersonal rejection sensitivity as an alternate primary feature. A
      reformulated model also suggested lifetime panic disorder and social phobia as
      higher-order determinants of atypical features in major depressive disorder.
      Additional analyses of criteria suggested that interpersonal rejection
      sensitivity and leaden paralysis had a phenomenological base in anxiety, that
      mood reactivity was linked with irritability, and that neither weight gain nor
      hypersomnia were clearly aligned with anxiety or depression, raising questions
      about their status as symptoms. CONCLUSIONS: The current definition and modeling
      of the DSM-IV atypical features specifier for a major depressive episode in major
      depressive disorder appears problematic. As suggested by earlier descriptions of
      atypical depression, certain expressions of anxiety may have primacy, and some
      clinical features associated with the DSM-IV model may be adaptive homeostatic
      responses rather than pathological symptoms.

PMID- 12202265
TI  - Gibraltar shattered.

PMID- 12202266
TI  - Prompt identification of Alzheimer's disease with brain PET imaging of a woman
      with multiple previous diagnoses of other neuropsychiatric conditions.

PMID- 12202268
TI  - Effects of ketamine on leading saccades during smooth-pursuit eye movements may
      implicate cerebellar dysfunction in schizophrenia.
AB  - OBJECTIVE: Ketamine has proved a useful probe in the study of schizophrenia.
      Recent studies have shown that ketamine causes abnormalities in eye tracking
      similar to those seen in patients with schizophrenia. The authors examined the
      effects of ketamine on leading saccadic eye movements, a specific component of
      the smooth-pursuit response shown to be abnormal in schizophrenia patients and
      their relatives. METHOD: Twelve normal healthy volunteers received a 0.1 mg/kg
      bolus injection of ketamine or placebo in double-blind fashion during a smooth
      pursuit eye-movement task. The number of leading saccades and the ratios of
      leading saccades to smooth-pursuit response time and to total saccadic eye
      movement time were measured. RESULTS: Ketamine significantly increased the number
      of leading saccades and increased the leading saccade ratios for more slowly
      moving targets. Similar nonsignificant effects were noted at higher target
      speeds. Ketamine-induced abnormalities were similar to those observed in
      relatives of schizophrenia patients under drug-free conditions. CONCLUSIONS:
      These results suggest that neurotransmission mediated by N-methyl-D-aspartate
      (NMDA) is involved in eye-tracking abnormalities. The generation of disruptive
      leading saccades during smooth pursuit is thought to be mediated by frontal
      thalamic-cerebellar circuitry. Evidence that the locus of this and other ketamine
      induced smooth-pursuit eye-movement deficits involves NMDA receptor functioning
      in the cerebellum is suggested.

PMID- 12202269
TI  - Cortical and subcortical gray matter abnormalities in schizophrenia determined
      through structural magnetic resonance imaging with optimized volumetric voxel
      based morphometry.
AB  - OBJECTIVE: Structural neuroimaging studies have suggested an association between
      schizophrenia and abnormalities in brain morphology such as ventricular
      enlargement and differences in gray matter distribution. Less consistently
      reported are findings of regional abnormalities such as selective differences in
      thalamic volume. The authors applied an unbiased technique to test for
      differences in cerebral morphometry between patients with schizophrenia and
      matched comparison subjects. METHOD: T(1)-weighted images from 20 schizophrenic
      patients and matched comparison subjects were processed by using optimized
      automated voxel-based morphometry within multiple linear regression analyses.
      RESULTS: Global differences in gray matter volume were seen between the
      schizophrenic and comparison subjects, with selective regional gray matter
      differences noted in the mediodorsal thalamus and across cortical regions,
      including the ventral and medial prefrontal cortices. Within the schizophrenic
      subjects, a relationship was observed between gray matter volume loss in the
      medial prefrontal cortex and a positive family history of schizophrenia. There
      was no significant difference between patients and comparison subjects in rates
      of proportional gray matter reduction with age. CONCLUSIONS: These observations
      confirm an association between thalamocortical morphometric abnormalities and
      schizophrenia, consistent with theoretical models of primary pathoetiological
      dysfunction in filtering, integration, and information transfer processes in
      patients with schizophrenia.

PMID- 12202270
TI  - Intact suppression of increased false recognition in schizophrenia.
AB  - OBJECTIVE: Recognition memory is impaired in patients with schizophrenia, as they
      rely largely on item familiarity, rather than conscious recollection, to make
      mnemonic decisions. False recognition of novel items (foils) is increased in
      schizophrenia and may relate to this deficit in conscious recollection. By
      studying pictures of the target word during encoding, healthy adults can suppress
      false recognition. This study examined the effect of pictorial encoding on
      subsequent recognition of repeated foils in patients with schizophrenia. METHOD:
      The study included 40 patients with schizophrenia and 32 healthy comparison
      subjects. After incidental encoding of 60 words or pictures, subjects were tested
      for recognition of target items intermixed with 60 new foils. These new foils
      were subsequently repeated following either a two- or 24-word delay. Subjects
      were instructed to label these repeated foils as new and not to mistake them for
      old target words. RESULTS: Schizophrenic patients showed greater overall false
      recognition of repeated foils. The rate of false recognition of repeated foils
      was lower after picture encoding than after word encoding. Despite higher levels
      of false recognition of repeated new items, patients and comparison subjects
      demonstrated a similar degree of false recognition suppression after picture, as
      compared to word, encoding. CONCLUSIONS: Patients with schizophrenia displayed
      greater false recognition of repeated foils than comparison subjects, suggesting
      both a decrement of item- (or source-) specific recollection and a consequent
      reliance on familiarity in schizophrenia. Despite these deficits, presenting
      pictorial information at encoding allowed schizophrenic subjects to suppress
      false recognition to a similar degree as the comparison group, implying the
      intact use of a high-level cognitive strategy in this population.

PMID- 12202271
TI  - Contributions of genetic risk and fetal hypoxia to hippocampal volume in patients
      with schizophrenia or schizoaffective disorder, their unaffected siblings, and
      healthy unrelated volunteers.
AB  - OBJECTIVE: The authors examined in an epidemiologic sample the contributions of
      genetic predisposition and history of fetal hypoxia to hippocampal volume in
      patients with psychosis. METHOD: High-resolution magnetic resonance imaging was
      used to measure hippocampal volumes in 72 psychotic probands (60 with
      schizophrenia and 12 with schizoaffective disorder, ascertained so as to be
      representative of all such probands in a Helsinki birth cohort), 58 nonpsychotic
      full siblings of the probands, and 53 demographically similar healthy comparison
      subjects with no family history of psychosis. RESULTS: Hippocampal volume
      differences occurred in a stepwise fashion with each increase in genetic load for
      schizophrenia. The probands had smaller hippocampal volumes than did their full
      siblings, who in turn had smaller hippocampal volumes than did the healthy
      comparison subjects. Among the probands, smaller hippocampal volumes were seen in
      those who experienced fetal hypoxia than in those who did not, a difference not
      noted within the other two groups. Finally, within the
      schizophrenic/schizoaffective disorder patients, smaller hippocampal volumes
      correlated positively with age at onset independent of duration of illness.
      CONCLUSIONS: These findings suggest that in patients with schizophrenia spectrum
      disorders, hippocampal volume is influenced in part by schizophrenia
      susceptibility genes and an interaction of these genes with fetal hypoxia. They
      further suggest that hippocampal volume in schizophrenia or schizoaffective
      disorder may be linked to time of disease onset.

PMID- 12202272
TI  - Smaller left Heschl's gyrus volume in patients with schizotypal personality
      disorder.
AB  - OBJECTIVE: Individuals with schizophrenia spectrum disorders evince similar
      genetic, neurotransmitter, neuropsychological, electrophysiological, and
      structural abnormalities. Magnetic resonance imaging (MRI) studies have shown
      smaller gray matter volume in patients with schizotypal personality disorder than
      in matched comparison subjects in the left superior temporal gyrus, an area
      important for language processing. In a further exploration, the authors studied
      two components of the superior temporal gyrus: Heschl's gyrus and the planum
      temporale. METHOD: MRI scans were acquired from 21 male, neuroleptic-naive
      subjects recruited from the community who met DSM-IV criteria for schizotypal
      personality disorder and 22 male comparison subjects similar in age. Eighteen of
      the 21 subjects with schizotypal personality disorder had additional comorbid,
      nonpsychotic diagnoses. The superior temporal gyrus was manually delineated on
      coronal images with subsequent identification of Heschl's gyrus and the planum
      temporale. Exploratory correlations between region of interest volumes and
      neuropsychological measures were also performed. RESULTS: Left Heschl's gyrus
      gray matter volume was 21% smaller in the schizotypal personality disorder
      subjects than in the comparison subjects, a difference that was not associated
      with the presence of comorbid axis I disorders. There were no between-group
      volume differences in right Heschl's gyrus or in the right or left planum
      temporale. Exploratory analyses also showed a correlation between poor logical
      memory and smaller left Heschl's gyrus volume. CONCLUSIONS: Smaller left Heschl's
      gyrus gray matter volume in subjects with schizotypal personality disorder may
      help to explain the previously reported abnormality in the left superior temporal
      gyrus and may be a vulnerability marker for schizophrenia spectrum disorders.

PMID- 12202274
TI  - From conventional to atypical antipsychotics and back: dynamic processes in the
      diffusion of new medications.
AB  - OBJECTIVE: Between 1994 and 1997, the Food and Drug Administration approved three
      new atypical antipsychotic medications for the treatment of schizophrenia. The
      authors tracked prescription patterns for these medications, an atypical
      antipsychotic approved in 1989, and conventional neuroleptics in the Department
      of Veterans Affairs (VA) to determine how the new drugs have diffused in a
      national health care system. METHOD: Pharmacy claims data were collected for all
      patients with a diagnosis of schizophrenia in the VA. Patients who received
      stable 3-month prescriptions of any antipsychotic medication were followed over
      fiscal year 2000 to determine how often they were switched to another drug, how
      much time elapsed before they were switched, the drug to which they were
      switched, and whether they subsequently switched back to the original drug.
      RESULTS: Of the 21,873 patients with schizophrenia who had stable 3-month
      prescriptions of any antipsychotic medication, 5,426 (25%) had their medications
      switched during the next year. Half of these patients (N=2,708) switched back to
      their original drug, usually within 30 days. Patients who had stable
      prescriptions of clozapine were the least likely to be switched (18%), and
      patients who had stable prescriptions of quetiapine were the most likely to be
      switched (37%). When medications were switched, 35% of the patients were switched
      to olanzapine; only 1% were switched to clozapine, and only 14% were switched to
      quetiapine. CONCLUSIONS: Pharmacotherapy for schizophrenia is a dynamic process.
      One-quarter of patients with stable antipsychotic drug regimens had their
      medication changed within 1 year. Quetiapine was the least prescribed of the
      newer drugs. These results suggest that it is important that all of these
      medications are included in formularies.

PMID- 12202273
TI  - Paternal age and risk of schizophrenia in adult offspring.
AB  - OBJECTIVE: The study examined the relation between paternal age at the time of
      birth and risk of schizophrenia in the adult offspring. METHOD: Data from the
      birth cohort of the Prenatal Determinants of Schizophrenia study were used in
      this study. Virtually all members of this birth cohort had prospective
      information about paternal age at the time of the offspring's birth. Subjects
      with schizophrenia and other schizophrenia spectrum disorders (N=71) among
      members of this birth cohort were previously ascertained. In separate analyses,
      paternal age was modeled as a continuous variable and as a categorical variable,
      and its relation with the risk of adult schizophrenia and other schizophrenia
      spectrum disorders and with the risk of schizophrenia separately were examined.
      RESULTS: There was a marginally significant, monotonic association between
      advancing paternal age and risk of adult schizophrenia and schizophrenia spectrum
      disorders. The association held after the analysis controlled for the effects of
      maternal age and other potential confounders. Similar results were observed when
      only subjects with schizophrenia were included in the analysis. CONCLUSIONS:
      Advanced paternal age at the time of birth of the offspring may be a risk factor
      for adult schizophrenia.

PMID- 12202275
TI  - Predicting adolescent violence: impact of family history, substance use,
      psychiatric history, and social adjustment.
AB  - OBJECTIVE: The aim of this study was to provisionally develop an efficient
      screening method to detect adolescents at high risk for committing a violent act
      by young adulthood. In addition, the authors sought to use this screening
      instrument, in conjunction with child and parent psychopathology and substance
      abuse data, to determine the accuracy of violent outcome predictions. METHOD: The
      probands were men with a lifetime history of DSM-III-R substance use disorder
      (N=38) and men with no adult psychiatric disorder (N=61). Their biological sons
      were studied at two time points. At age 12-14, the offspring completed a 13-item
      Violence Proneness Scale, which was derived by using items from the revised Drug
      Use Screening Inventory. The occurrence of violent acts was then assessed at a
      follow-up evaluation when the offspring were 19 years of age. RESULTS: Among the
      offspring, a DSM-III-R axis I psychiatric disorder and a Violence Proneness Scale
      score of 10 or higher at age 12-14 predicted a violent outcome by age 19. The
      overall accuracy of prediction was 77%. Sensitivity was 81%, and specificity was
      76%. Substance use disorder or psychopathology in the probands or substance use
      frequency in the children did not contribute to the prediction of violence.
      CONCLUSIONS: The brief Violence Proneness Scale, which measures school and peer
      adjustment, in conjunction with a childhood psychiatric history may constitute an
      efficient screening procedure for identifying youth who are at high risk for
      committing acts of violence.

PMID- 12202276
TI  - Unmet need for mental health care among U.S. children: variation by ethnicity and
      insurance status.
AB  - OBJECTIVE: Policy discussions regarding the mental health needs of children and
      adolescents emphasize a lack of use of mental health services among youth, but
      few national estimates are available. The authors use three national data sets
      and examine ethnic disparities in unmet need (defined as having a need for mental
      health evaluation but not using any services in a 1-year period) to provide such
      estimates. METHOD: The authors conducted secondary data analyses in three
      nationally representative household surveys fielded in 1996-1998: the National
      Health Interview Survey, the National Survey of American Families, and the
      Community Tracking Survey. They determined rates of mental health service use by
      children and adolescents 3-17 years of age and differences by ethnicity and
      insurance status. Among the children defined as in need of mental health
      services, defined by an estimator of mental health problems (selected items from
      the Child Behavior Checklist), they examined the association of unmet need with
      ethnicity and insurance status. RESULTS: In a 12-month period, 2%-3% of children
      3-5 years old and 6%-9% of children and adolescents 6-17 years old used mental
      health services. Of children and adolescents 6-17 years old who were defined as
      needing mental health services, nearly 80% did not receive mental health care.
      Controlling for other factors, the authors determined that the rate of unmet need
      was greater among Latino than white children and among uninsured than publicly
      insured children. CONCLUSIONS: These findings reveal that most children who need
      a mental health evaluation do not receive services and that Latinos and the
      uninsured have especially high rates of unmet need relative to other children.
      Rates of use of mental health services are extremely low among preschool
      children. Research clarifying the reasons for high rates of unmet need in
      specific groups can help inform policy and clinical programs.

PMID- 12202277
TI  - Differential effect of environmental adversity by gender: Rutter's index of
      adversity in a group of boys and girls with and without ADHD.
AB  - OBJECTIVE: This study examined the effect of gender in mediating the association
      between environmental adversity and the risk of attention deficit hyperactivity
      disorder (ADHD) and associated impairments. METHOD: The authors studied 280 ADHD
      and 242 healthy comparison probands of both genders who were between the ages of
      6 and 17 years. They tested the association between Rutter's indicators of
      adversity (including family conflict, social class, family size, maternal
      psychopathology, and paternal criminality) and ADHD, comorbidity, and
      functioning. RESULTS: Greater levels of environmental adversity were associated
      with a greater risk for ADHD and other comorbidity in both genders in a dose
      dependent fashion. However, learning disability and global functioning were
      modified by gender, with more detrimental effects observed in boys than in girls.
      Low social class, maternal psychopathology, and family conflict were
      significantly associated with psychopathology and functional impairment in the
      probands, with control for gender, parental ADHD, proband ADHD status, and
      maternal smoking during pregnancy. CONCLUSIONS: Psychosocial adversity in general
      and low social class, maternal psychopathology, and family conflict in particular
      increased the risk for ADHD and associated morbidity independently of gender and
      other risk factors, but gender modified the risk for adverse cognitive and
      interpersonal outcomes; boys were more vulnerable to the disorder than girls.
      Because of the difficulties in separating the effects of genetics from
      environment, these results must be interpreted as provisional until confirmation
      from twin and adoption studies.

PMID- 12202278
TI  - Physician empathy: definition, components, measurement, and relationship to
      gender and specialty.
AB  - OBJECTIVE: There is a dearth of empirical research on physician empathy despite
      its mediating role in patient-physician relationships and clinical outcomes. This
      study was designed to investigate the components of physician empathy, its
      measurement properties, and group differences in empathy scores. METHOD: A
      revised version of the Jefferson Scale of Physician Empathy (with 20 Likert-type
      items) was mailed to 1,007 physicians affiliated with the Jefferson Health System
      in the greater Philadelphia region; 704 (70%) responded. Construct validity,
      reliability of the empathy scale, and the differences on mean empathy scores by
      physicians' gender and specialty were examined. RESULTS: Three meaningful factors
      emerged (perspective taking, compassionate care, and standing in the patient's
      shoes) to provide support for the construct validity of the empathy scale that
      was also found to be internally consistent with relatively stable scores over
      time. Women scored higher than men to a degree that was nearly significant. With
      control for gender, psychiatrists scored a mean empathy rating that was
      significantly higher than that of physicians specializing in anesthesiology,
      orthopedic surgery, neurosurgery, radiology, cardiovascular surgery, obstetrics
      and gynecology, and general surgery. No significant difference was observed on
      empathy scores among physicians specializing in psychiatry, internal medicine,
      pediatrics, emergency medicine, and family medicine. CONCLUSIONS: Empathy is a
      multidimensional concept that varies among physicians and can be measured with a
      psychometrically sound tool. Implications for specialty selection and career
      counseling are discussed.

PMID- 12202279
TI  - A hazardous profession: war, journalists, and psychopathology.
AB  - OBJECTIVE: War journalists often confront situations of extreme danger in their
      work. Despite this, information on their psychological well-being is lacking.
      METHOD: The authors used self-report questionnaires to assess 140 war
      journalists, who recorded symptoms of posttraumatic stress disorder (PTSD) (with
      the Impact of Event Scale-Revised), depression (with the Beck Depression
      Inventory-II), and psychological distress (with the 28-item General Health
      Questionnaire). To control for stresses generic to all journalism, the authors
      used the same instruments to assess 107 journalists who had never covered war. A
      second phase of the study involved interviews with one in five journalists from
      both groups, using the Structured Clinical Interview for Axis I DSM-IV Disorders.
      RESULTS: The rates of response to the self-report questionnaires were
      approximately 80% for both groups. There were no demographic differences between
      groups. Both male and female war journalists had significantly higher weekly
      alcohol consumption. The war journalists had higher scores on the Impact of Event
      Scale and the Beck Depression Inventory. Their lifetime prevalence of PTSD was
      28.6%, and the rates were 21.4% for major depression and 14.3% for substance
      abuse. War journalists were not, however, more likely to receive treatment for
      these disorders. CONCLUSIONS: War journalists have significantly more psychiatric
      difficulties than journalists who do not report on war. In particular, the
      lifetime prevalence of PTSD is similar to rates reported for combat veterans,
      while the rate of major depression exceeds that of the general population. These
      results, which need replicating, should alert news organizations that significant
      psychological distress may occur in many war journalists and often goes
      untreated.

PMID- 12202280
TI  - Mental disorders among U.S. military personnel in the 1990s: association with
      high levels of health care utilization and early military attrition.
AB  - OBJECTIVE: Epidemiological studies have shown that mental disorders are
      associated with reduced health-related quality of life, high levels of health
      care utilization, and work absenteeism. However, measurement of the burden of
      mental disorders by using population-based methods in large working populations,
      such as the U.S. military, has been limited. METHOD: Analysis of hospitalizations
      among all active-duty military personnel (16.4 million person-years) from 1990 to
      1999 and ambulatory visits from 1996 to 1999 was conducted by using the Defense
      Medical Surveillance System. Rates of hospitalization, ambulatory visits, and
      attrition from military service were compared for persons with mental disorder
      diagnoses and those with diagnoses in 15 other ICD-9 disease categories. RESULTS:
      Mental disorders was the leading category of discharge diagnoses among men and
      the second leading category among women; 13% of all hospitalizations and 23% of
      all inpatient bed days were attributed to mental disorders. Six percent of the
      military population received ambulatory services for mental disorders annually in
      1998 and 1999. Among a 1-year cohort of personnel, 47% of those hospitalized for
      the first time for a mental disorder left military service within 6 months. This
      attrition rate was significantly different from the rate of only 12% after
      hospitalization for any of the 15 other disease categories (range=11%-18%)
      (relative risk=4.04, 95% confidence interval=3.91-4.17). The difference remained
      significant after controlling for effects of age, gender, and duration of
      service. CONCLUSIONS: Mental disorders appear to represent the most important
      source of medical and occupational morbidity among active-duty U.S. military
      personnel. These findings provide new population-based evidence that mental
      disorders are common, disabling, and costly to society.

PMID- 12202281
TI  - Mental disorders and quality of diabetes care in the veterans health
      administration.
AB  - OBJECTIVE: The population of persons with mental disorders is potentially
      vulnerable to poor quality of medical care. This study examined the relationship
      between mental disorders and quality of diabetes care in a national sample of
      veterans. METHOD: Chart-abstracted quality data were merged with outpatient and
      inpatient administrative database records for a sample of veterans with diabetes
      who had at least three outpatient visits in the previous year (N=38,020). Mental
      health diagnoses were identified by use of the administrative data. Quality of
      diabetes care was assessed with five indicators by chart documentation: annual
      foot inspection, pedal pulses examination, foot sensory examination, retina
      examination, and glycated hemoglobin determination. RESULTS: Approximately a
      quarter of the sample had a diagnosed mental disorder (23.7% with psychiatric
      disorder only, 1.3% with substance use disorder only, and 2.6% with a dual
      diagnosis). Overall rates of receipt for the indicators were higher than national
      benchmarks for all patient subgroups, ranging from 70.8% for retina examination
      to 95.0% for foot inspection. Rates for both retina examination and foot sensory
      examination differed significantly by mental health status, mainly because of
      lower rates among those with a substance use disorder. The associations remained
      significant in multivariate generalized estimating equation analyses that
      controlled for demographic characteristics, health status, use of medical
      services, and hospital-level characteristics. CONCLUSIONS: Rates for secondary
      prevention of diabetes were remarkably high at Department of Veterans Affairs
      medical centers, although patients with mental disorders (particularly substance
      use disorders) were somewhat less likely to receive some of the recommended
      interventions.

PMID- 12202282
TI  - Paternal age and schizophrenia: further support for an association.
AB  - OBJECTIVE: Advanced paternal age has been proposed as a risk factor for later
      development of schizophrenia in offspring, although studies are not conclusive.
      De novo mutations arising in paternal germ cells have been suggested as the
      underlying mechanism. METHOD: The hypothesized association was investigated in a
      population-based case-control study comprising 524 subjects with schizophrenia
      and 1,043 matched comparison subjects selected from registers. Birth records with
      data on parental age were retrieved manually. Odds ratios were computed, with
      controls for maternal age, parity, marital status, socioeconomic status, maternal
      psychotic illness, and obstetric complications. RESULTS: The odds of
      schizophrenia in offspring of fathers 45 years old or older were 2.8 times as
      great as in offspring of fathers aged 20-24 years. CONCLUSIONS: These findings
      confirm previous reports of a higher risk for schizophrenia associated with
      advanced paternal age. They may be of interest for further studies on the genetic
      mechanisms behind schizophrenia.

PMID- 12202283
TI  - Association of risperidone treatment response with a polymorphism in the 5-HT(2A)
      receptor gene.
AB  - OBJECTIVE: This study investigated the effect of the 102-T/C polymorphism in the
      5-HT(2A) receptor gene on risperidone efficacy. METHOD: One hundred Han Chinese
      patients with acutely exacerbated schizophrenia were given risperidone for up to
      42 days. The patients were genotyped for 5-HT(2A) polymorphisms. Psychopathology
      was measured biweekly with the Positive and Negative Syndrome Scale while the
      patients were taking risperidone. Generalized estimating equation methods were
      used to analyze the effects of treatment duration, T/C genotypes, and other
      prognostic factors on Positive and Negative Syndrome Scale performance. RESULTS:
      Patients with the C/C genotype had lower total scores, negative subscale scores,
      and general psychopathology scores but not positive subscale scores on the
      Positive and Negative Syndrome Scale than patients with the 102-T/C genotype.
      Patients with the T/C and T/T genotypes had comparable total and subscale scores.
      The number of previous hospitalizations and the dose of risperidone also affected
      Positive and Negative Syndrome Scale total scores. CONCLUSIONS: These results
      suggest that variations in the 5-HT(2A) receptor gene may influence individual
      responses to risperidone.

PMID- 12202284
TI  - Randomized, placebo-controlled study of ethyl-eicosapentaenoic acid as
      supplemental treatment in schizophrenia.
AB  - OBJECTIVE: The study investigated the efficacy and tolerability of ethyl
      eicosapentaenoic acid (E-EPA) as add-on treatment in chronic, severe
      schizophrenia. METHOD: A randomized, parallel-group, double-blind, placebo
      controlled, fixed-dose, add-on study was conducted over 12 weeks. Forty patients
      with persistent symptoms after at least 6 months of stable antipsychotic
      treatment received E-EPA or placebo, in addition to their existing treatment.
      RESULTS: At 12 weeks, the E-EPA group had significantly greater reduction of
      Positive and Negative Syndrome Scale total scores and of dyskinesia scores than
      the placebo group. CONCLUSIONS: EPA may be an effective and well-tolerated add-on
      treatment in schizophrenia.

PMID- 12202285
TI  - Interrater reliability in clinical trials of depressive disorders.
AB  - OBJECTIVE: The goal of this study was to review the reported methods of rater
      training, assessment of interrater reliability, and rater drift in clinical
      trials of treatments for depressive disorders. METHOD: Two psychiatrists
      independently identified all original reports of clinical trials relevant to
      depressive disorders published between 1996 and 2000 in the American Journal of
      Psychiatry and the Archives of General Psychiatry. Reported methods of rater
      training, assessment of interrater reliability, and rater drift were
      systematically summarized. RESULTS: Sixty-three original papers met criteria for
      inclusion. Only 11 (17%) of the studies reported the number of raters. Only two
      (9%) of the 22 multicenter and four (10%) of the 41 single-center trials
      documented rater training. Only nine (22%) of the single-center trials and three
      (14%) of the multicenter trials reported interrater reliability, despite a median
      number of five raters (range=2-20). Only three (5%) of the 63 articles reported
      rater drift. CONCLUSIONS: Few published reports of clinical trials of treatments
      for depressive disorders document adequately the number of raters, rater
      training, assessment of interrater reliability, and rater drift.

PMID- 12202286
TI  - Suicide attempts in substance abusers: effects of major depression in relation to
      substance use disorders.
AB  - OBJECTIVE: The authors' goal was to investigate whether subtypes of DSM-IV
      depression predict suicidal behavior among patients with substance dependence.
      METHOD: Major depression among 602 patients with substance dependence was
      classified as occurring before dependence, during abstinence, or exclusively
      during periods of substance use. Analyses of patients with the three types of
      depression included logistic and linear regression. RESULTS: All three types of
      depression increased the risk for making a suicide attempt. Major depression that
      occurred before the patient became substance dependent predicted severity of
      suicidal intent. Major depression that occurred during abstinence predicted
      number of attempts. CONCLUSIONS: These results suggest the importance of
      establishing DSM-IV subtypes of depression based on the timing of the occurrence
      of depression in relation to substance dependence in evaluating suicidal risk
      among substance-dependent patients.

PMID- 12202287
TI  - Dissociation, childhood trauma, and ataque de nervios among Puerto Rican
      psychiatric outpatients.
AB  - OBJECTIVE: This study examined the relationships of dissociation and childhood
      trauma with ataque de nervios. METHOD: Forty Puerto Rican psychiatric outpatients
      were evaluated for frequency of ataque de nervios, dissociative symptoms,
      exposure to trauma, and mood and anxiety psychopathology. Blind conditions were
      maintained across assessments. Data for 29 female patients were analyzed.
      RESULTS: Among these 29 patients, clinician-rated dissociative symptoms increased
      with frequency of ataque de nervios. Dissociative Experiences Scale scores and
      diagnoses of panic disorder and dissociative disorders were also associated with
      ataque frequency, before corrections were made for multiple comparisons. The rate
      of childhood trauma was uniformly high among the patients and showed no
      relationship to dissociative symptoms and disorder or number of ataques.
      CONCLUSIONS: Frequent ataques de nervios may, in part, be a marker for
      psychiatric disorders characterized by dissociative symptoms. Childhood trauma
      per se did not account for ataque status in this group of female outpatients.

PMID- 12202288
TI  - Ibuprofen and psychotic exacerbation.

PMID- 12202289
TI  - Ziprasidone alternative for olanzapine-induced hyperglycemia.

PMID- 12202290
TI  - Myocarditis with quetiapine.

PMID- 12202291
TI  - Rhabdomyolysis with simvastatin and nefazodone.

PMID- 12202292
TI  - Prolactin elevation with quetiapine.

PMID- 12202294
TI  - Pregnancy outcomes in schizophrenia.

PMID- 12202310
TI  - Reducing risk of injury due to exercise.

PMID- 12202311
TI  - Treatment of advanced non-small cell lung cancer.

PMID- 12202312
TI  - Staffing by numbers in the NHS.

PMID- 12202315
TI  - World summit hits hurdles on opening day.

PMID- 12202313
TI  - Treating head injuries.

PMID- 12202323
TI  - Health can take precedence over trade issues, says report.

PMID- 12202324
TI  - West Nile virus spreads in United States.

PMID- 12202325
TI  - Local treatments for cutaneous warts: systematic review.
AB  - OBJECTIVE: To assess the evidence for the efficacy of local treatments for
      cutaneous warts. METHODS: Systematic review of randomised controlled trials. MAIN
      OUTCOMES MEASURES: Total clearance of warts and adverse effects such as
      irritation, pain, and blistering. STUDY SELECTION: Randomised controlled trials
      of any local treatment for uncomplicated cutaneous warts. All published and
      unpublished material was considered, with no restriction on date or language.
      RESULTS: 50 included trials provided generally weak evidence because of poor
      methods and reporting. The best evidence was for topical treatments containing
      salicylic acid. Data pooled from six placebo controlled trials showed a cure rate
      of 75% (144 of 191) in cases compared with 48% (89 of 185) in controls (odds
      ratio 3.91, 95% confidence interval 2.40 to 6.36). Some evidence for the efficacy
      of contact immunotherapy was provided by two small trials comparing
      dinitrochlorobenzene with placebo. Evidence for the efficacy of cryotherapy was
      limited. No consistent evidence was found for the efficacy of intralesional
      bleomycin, and only limited evidence was found for the efficacy of topical
      fluorouracil, intralesional interferons, photodynamic therapy, and pulsed dye
      laser. CONCLUSIONS: Reviewed trials of local treatments for cutaneous warts were
      highly variable in methods and quality, and there was a paucity of evidence from
      randomised, placebo controlled trials on which to base the rational use of the
      treatments. There is good evidence that topical treatments containing salicylic
      acid have a therapeutic effect and some evidence for the efficacy of
      dinitrochlorobenzene. Less evidence was found for the efficacy of all the other
      treatments reviewed, including cryotherapy.

PMID- 12202326
TI  - Immediate versus delayed palliative thoracic radiotherapy in patients with
      unresectable locally advanced non-small cell lung cancer and minimal thoracic
      symptoms: randomised controlled trial.
AB  - OBJECTIVE: To determine whether patients with locally advanced non-small cell
      lung cancer unsuitable for resection or radical radiotherapy, and with minimal
      thoracic symptoms, should be given palliative thoracic radiotherapy immediately
      or as needed to treat symptoms. DESIGN: Multicentre randomised controlled trial.
      SETTING: 23 centres in the United Kingdom, Ireland, and South Africa.
      PARTICIPANTS: 230 patients with previously untreated, non-small cell lung cancer
      that is locally too advanced for resection or radical radiotherapy with curative
      intent, with minimal thoracic symptoms, and with no indication for immediate
      thoracic radiotherapy. INTERVENTIONS: All patients were given supportive
      treatment and were randomised to receive palliative thoracic radiotherapy either
      immediately or delayed until needed to treat symptoms. The recommended regimens
      were 17 Gy in two fractions one week apart or 10 Gy as a single dose. MAIN
      OUTCOME MEASURES: Primary--patients alive and without moderate or severe cough,
      chest pain, haemoptysis, or dyspnoea six months from randomisation, as recorded
      by clinicians. Secondary--quality of life, adverse events, survival. RESULTS:
      From December 1992 to May 1999, 230 patients were randomised. 104/115 of the
      patients in the immediate treatment group received thoracic radiotherapy (90
      received one of the recommended regimens). In the delayed treatment group, 48/115
      (42%) patients received thoracic radiotherapy (29 received one of the recommended
      regimens); 64 (56%) died without receiving thoracic radiotherapy; the remaining
      three (3%) were alive at the end of the study without having received the
      treatment. For patients who received thoracic radiotherapy, the median time to
      start was 15 days in the immediate treatment group and 125 days in the delayed
      treatment group. The primary outcome measure was achieved in 28% of the immediate
      treatment group and 26% of patients from the delayed treatment group (27/97 and
      27/103, respectively; absolute difference 1.6%, 95% confidence interval -10.7% to
      13.9%). No evidence of a difference was observed between the two treatment groups
      in terms of activity level, anxiety, depression, and psychological distress, as
      recorded by the patients. Adverse events were more common in the immediate
      treatment group. Neither group had a survival advantage (hazard ratio 0.95, 0.73
      to 1.24; P=0.71). Median survival was 8.3 months and 7.9 months, and the survival
      rates were 31% and 29% at 12 months, for the immediate and delayed treatment
      groups, respectively. CONCLUSION: In minimally symptomatic patients with locally
      advanced non-small cell lung cancer, no persuasive evidence was found to indicate
      that giving immediate palliative thoracic radiotherapy improves symptom control,
      quality of life, or survival when compared with delaying until symptoms require
      treatment.

PMID- 12202327
TI  - Effects of stretching before and after exercising on muscle soreness and risk of
      injury: systematic review.
AB  - OBJECTIVE: To determine the effects of stretching before and after exercising on
      muscle soreness after exercise, risk of injury, and athletic performance. METHOD:
      Systematic review. DATA SOURCES: Randomised or quasi-randomised studies
      identified by searching Medline, Embase, CINAHL, SPORTDiscus, and PEDro, and by
      recursive checking of bibliographies. MAIN OUTCOME MEASURES: Muscle soreness,
      incidence of injury, athletic performance. RESULTS: Five studies, all of moderate
      quality, reported sufficient data on the effects of stretching on muscle soreness
      to be included in the analysis. Outcomes seemed homogeneous. Stretching produced
      small and statistically non-significant reductions in muscle soreness. The pooled
      estimate of reduction in muscle soreness 24 hours after exercising was only 0.9
      mm on a 100 mm scale (95% confidence interval -2.6 mm to 4.4 mm). Data from two
      studies on army recruits in military training show that muscle stretching before
      exercising does not produce useful reductions in injury risk (pooled hazard ratio
      0.95, 0.78 to 1.16). CONCLUSIONS: Stretching before or after exercising does not
      confer protection from muscle soreness. Stretching before exercising does not
      seem to confer a practically useful reduction in the risk of injury, but the
      generality of this finding needs testing. Insufficient research has been done
      with which to determine the effects of stretching on sporting performance.

PMID- 12202328
TI  - Follow up of people fitted with hearing aids after adult hearing screening: the
      need for support after fitting.

PMID- 12202329
TI  - Consultation length in general practice: cross sectional study in six European
      countries.
AB  - OBJECTIVES: To compare determinants of consultation length discussed in the
      literature with those found in consultations with general practitioners from
      different European countries; to explore the determinants of consultation length,
      particularly the effect of doctors' and patients' perceptions of psychosocial
      aspects. DESIGN: Analysis of videotaped consultations of general practitioners
      from the Eurocommunication study and of questionnaires completed by doctors and
      by patients. SETTING: General practices in six European countries. PARTICIPANTS:
      190 general practitioners and 3674 patients. RESULTS: In a multilevel analysis
      with three levels (country, general practitioner, and patient), country and
      doctor variables contributed a similar amount to the total variance in
      consultation length (23% and 22%, respectively) and patient variables accounted
      for 55% of the variance. The variables used in the multilevel analysis explained
      25% of the total variation. The country in which the doctor practised, combined
      with the doctors' variables, was as important for the variance in consultation
      length as the variation between patients. Consultations in which psychosocial
      problems were considered important by the doctor and the patient lasted longer
      than consultations about biomedical problems only. The doctor's perception had
      more influence in this situation than the patient's. Consultation length is
      influenced by the patients' sex (women got longer consultations), whether the
      practice was urban or rural, the number of new problems discussed in the
      consultation (the more problems the longer the consultation), and the patient's
      age (the older the patient the longer the consultation). As a doctor's workload
      increased, the length of consultations decreased. The general practitioner's sex
      or age and patient's level of education were not related to the length of
      consultation. CONCLUSION: Consultation length is determined by variables related
      to the doctor and the doctor's country as well as by those related to patients.
      Women consulting in an urban practice with problems perceived as psychosocial
      have longer consultations than other patients.

PMID- 12202330
TI  - Acne vulgaris.

PMID- 12202331
TI  - Fatigue.

PMID- 12202332
TI  - Bone mineral density scans.

PMID- 12202333
TI  - Physician assistants in the United States.

PMID- 12202334
TI  - Social insurance--the right way forward for health care in the United Kingdom?
      For.

PMID- 12202335
TI  - Are trust doctors the new lost tribe?

PMID- 12202336
TI  - Peer review of statistics in medical research. Journal reviewers are even more
      baffled by sample size issues than grant proposal reviewers.

PMID- 12202337
TI  - Cases of polio in Nigeria are dropping.

PMID- 12202338
TI  - Editorial on epidemiology of HIV in China was misleading.

PMID- 12202340
TI  - Intermediate care is ageist.

PMID- 12202339
TI  - Trends in HIV, gonorrhoea, and syphilis. Screening for neurosyphilis is
      recommended.

PMID- 12202341
TI  - Selection of medical students. How can medical schools produce good doctors if
      political dogma restricts them?

PMID- 12202342
TI  - Acid, burns, and feeding tubes. Patients should not be allowed to lie in their
      own vomit: gastric acid burns.

PMID- 12202343
TI  - On Hippocrates. Hippocratic ideals are alive and well in 21st century.

PMID- 12202345
TI  - Applying the Working Time Directive to doctors in training.

PMID- 12202346
TI  - Making the European Working Time Directive a reality.

PMID- 12202347
TI  - Implementing the European Working Time directive on a national level.

PMID- 12202348
TI  - Education and training within the European Working Time Directive.

PMID- 12202349
TI  - The European Working Time Directive and the training of surgeons.

PMID- 12202350
TI  - The Dutch experience of implementing the European Working Time Directive.

PMID- 12202351
TI  - Trial by ordeal: ionic free energies in gramicidin.

PMID- 12202352
TI  - Regulation of actin dynamics in rapidly moving cells: a quantitative analysis.
AB  - We develop a mathematical model that describes key details of actin dynamics in
      protrusion associated with cell motility. The model is based on the dendritic
      nucleation hypothesis for lamellipodial protrusion in nonmuscle cells such as
      keratocytes. We consider a set of partial differential equations for diffusion
      and reactions of sequestered actin complexes, nucleation, and growth by
      polymerization of barbed ends of actin filaments, as well as capping and
      depolymerization of the filaments. The mechanical aspect of protrusion is based
      on an elastic polymerization ratchet mechanism. An output of the model is a
      relationship between the protrusion velocity and the number of filament barbed
      ends pushing the membrane. Significantly, this relationship has a local maximum:
      too many barbed ends deplete the available monomer pool, too few are insufficient
      to generate protrusive force, so motility is stalled at either extreme. Our
      results suggest that to achieve rapid motility, some tuning of parameters
      affecting actin dynamics must be operating in the cell.

PMID- 12202353
TI  - Molecular dynamics investigation of membrane-bound bundles of the channel-forming
      transmembrane domain of viral protein U from the human immunodeficiency virus HIV
      1.
AB  - Molecular dynamics (MD) simulations have been carried out on bundles of the
      channel-forming transmembrane (TM) domain of the viral protein U (VPU(1-27) and
      VPU(6-27)) from the human immunodeficiency virus (HIV-1). Simulations of
      hexameric and pentameric bundles of VPU(6-27) in an octane/water membrane mimetic
      system suggested that the pentamer is the preferred oligomer. Accordingly, an
      unconstrained pentameric helix bundle of VPU(1-27) was then placed in a hydrated
      palmitoyl-oleyl-3-n-glycero-phosphatidylethanolamine (POPE) lipid bilayer and its
      structural properties calculated from a 3-ns MD run. Some water molecules,
      initially inside the channel lumen, were expelled halfway through the simulation
      and the bundle adopted a conical structure reminiscent of previous MD results
      obtained for VPU(6-27) in an octane/water system. The pore constriction generated
      may correspond to a closed state of the channel and underlies the relocation of
      the W residue toward the pore lumen. The relative positions of the helices with
      respect to the bilayer and their interactions with the lipids are discussed. The
      observed structure is stabilized via specific interactions between the VPU
      helices and the carbonyl oxygen atoms of the lipid molecules, particularly at the
      Q and S residues.

PMID- 12202354
TI  - Exploring the propensities of helices in PrP(C) to form beta sheet using NMR
      structures and sequence alignments.
AB  - Neurodegenerative diseases induced by transmissible spongiform encephalopathies
      are associated with prions. The most spectacular event in the formation of the
      infectious scrapie form, referred to as PrP(Sc), is the conformational change
      from the predominantly alpha-helical conformation of PrP(C) to the PrP(Sc) state
      that is rich in beta-sheet content. Using sequence alignments and structural
      analysis of the available nuclear magnetic resonance structures of PrP(C), we
      explore the propensities of helices in PrP(C) to be in a beta-strand
      conformation. Comparison of a number of structural characteristics (such as
      solvent accessible area, distribution of (Phi, Psi) angles, mismatches in
      hydrogen bonds, nature of residues in local and nonlocal contacts, distribution
      of regular densities of amino acids, clustering of hydrophobic and hydrophilic
      residues in helices) between PrP(C) structures and a databank of "normal"
      proteins shows that the most unusual features are found in helix 2 (H2) (residues
      172-194) followed by helix 1 (H1) (residues 144-153). In particular, the C
      terminal residues in H2 are frustrated in their helical state. The databank of
      normal proteins consists of 58 helical proteins, 36 alpha+beta proteins, and 31
      beta-sheet proteins. Our conclusions are also substantiated by gapless threading
      calculations that show that the normalized Z-scores of prion proteins are similar
      to those of other alpha+beta proteins with low helical content. Application of
      the recently introduced notion of discordance, namely, incompatibility of the
      predicted and observed secondary structures, also points to the frustration of H2
      not only in the wild type but also in mutants of human PrP(C). This suggests that
      the instability of PrP(C) proteins may play a role in their being susceptible to
      the profound conformational change. Our analysis shows that, in addition to the
      previously proposed role for the segment (90-120) and possibly H1, the C-terminus
      of H2 and possibly N-terminus may play a role in the alpha-->beta transition. An
      implication of our results is that the ease of polymerization depends on the
      unfolding rate of the monomer. Sequence alignments show that helices in avian
      prion proteins (chicken, duck, crane) are better accommodated in a helical state,
      which might explain the absence of PrP(Sc) formation over finite time scales in
      these species. From this analysis, we predict that correlated mutations that
      reduce the frustration in the second half of helix 2 in mammalian prion proteins
      could inhibit the formation of PrP(Sc).

PMID- 12202355
TI  - Structural changes during the formation of early intermediates in the
      bacteriorhodopsin photocycle.
AB  - Early intermediates of bacteriorhodopsin's photocycle were modeled by means of ab
      initio quantum mechanical/molecular mechanical and molecular dynamics
      simulations. The photoisomerization of the retinal chromophore and the formation
      of photoproducts corresponding to the early intermediates were simulated by
      molecular dynamics simulations. By means of the quantum mechanical/molecular
      mechanical method, the resulting structures were refined and the respective
      excitation energies were calculated. Two sequential intermediates were found with
      absorption maxima that exhibit red shifts from the resting state. The
      intermediates were therefore assigned to the K and KL states. In K, the
      conformation of the retinal chromophore is strongly deformed, and the N--H bond
      of the Schiff base points almost perpendicular to the membrane normal toward Asp
      212. The strongly deformed conformation of the chromophore and weakened
      interaction of the Schiff base with the surrounding polar groups are the means by
      which the absorbed energy is stored. During the K-to-KL transition, the
      chromophore undergoes further conformational changes that result in the formation
      of a hydrogen bond between the N--H group of the Schiff base and Thr-89 as well
      as other rearrangements of the hydrogen-bond network in the vicinity of the
      Schiff base, which are suggested to play a key role in the proton transfer
      process in the later phase of the photocycle.

PMID- 12202356
TI  - Simulations of inositol phosphate metabolism and its interaction with InsP(3)
      mediated calcium release.
AB  - Inositol phosphates function as second messengers for a variety of extracellular
      signals. Ins(1,4,5)P(3) generated by phospholipase C-mediated hydrolysis of
      phosphatidylinositol bisphosphate, triggers numerous cellular processes by
      regulating calcium release from internal stores. The Ins(1,4,5)P(3) signal is
      coupled to a complex metabolic cascade involving a series of phosphatases and
      kinases. These enzymes generate a range of inositol phosphate derivatives, many
      of which have signaling roles of their own. We have integrated published
      biochemical data to build a mass action model for InsP(3) metabolism. The model
      includes most inositol phosphates that are currently known to interact with each
      other. We have used this model to study the effects of a G-protein coupled
      receptor stimulus that activates phospholipase C on the inositol phosphates. We
      have also monitored how the metabolic cascade interacts with Ins(1,4,5)P(3)
      mediated calcium release. We find temporal dynamics of most inositol phosphates
      to be strongly influenced by the elaborate networking. We also show that
      Ins(1,3,4,5)P(4) plays a key role in InsP(3) dynamics and allows for paired pulse
      facilitation of calcium release. Calcium oscillations produce oscillatory
      responses in parts of the metabolic network and are in turn temporally modulated
      by the metabolism of InsP(3).

PMID- 12202357
TI  - Structural microtubule cap: stability, catastrophe, rescue, and third state.
AB  - Microtubules polymerize from GTP-liganded tubulin dimers, but are essentially
      made of GDP-liganded tubulin. We investigate the tug-of-war resulting from the
      fact that GDP-liganded tubulin favors a curved configuration, but is forced to
      remain in a straight one when part of a microtubule. We point out that near the
      end of a microtubule, the proximity of the end shifts the balance in this tug-of
      war, with some protofilament bending as result. This somewhat relaxes the
      microtubule lattice near its end, resulting in a structural cap. This structural
      cap thus is a simple mechanical consequence of two well-established facts:
      protofilaments made of GDP-liganded tubulin have intrinsic curvature, and
      microtubules are elastic, made from material that can yield to forces, in casu
      its own intrinsic forces. We explore possible properties of this structural cap,
      and demonstrate 1) how it allows both polymerization from GTP-liganded tubulin
      and rapid depolymerization in its absence; 2) how rescue can occur; 3) how a
      third, meta-stable intermediate state is possible and can explain some
      experimental results; and 4) how the tapered tips observed at polymerizing
      microtubule ends are stabilized during growth, though unable to accommodate a
      lateral cap. This scenario thus supports the widely accepted GTP-cap model by
      suggesting a stabilizing mechanism that explains the many aspects of dynamic
      instability.

PMID- 12202358
TI  - Dynamic flux balance analysis of diauxic growth in Escherichia coli.
AB  - Flux Balance Analysis (FBA) has been used in the past to analyze microbial
      metabolic networks. Typically, FBA is used to study the metabolic flux at a
      particular steady state of the system. However, there are many situations where
      the reprogramming of the metabolic network is important. Therefore, the dynamics
      of these metabolic networks have to be studied. In this paper, we have extended
      FBA to account for dynamics and present two different formulations for dynamic
      FBA. These two approaches were used in the analysis of diauxic growth in
      Escherichia coli. Dynamic FBA was used to simulate the batch growth of E. coli on
      glucose, and the predictions were found to qualitatively match experimental data.
      The dynamic FBA formalism was also used to study the sensitivity to the objective
      function. It was found that an instantaneous objective function resulted in
      better predictions than a terminal-type objective function. The constraints that
      govern the growth at different phases in the batch culture were also identified.
      Therefore, dynamic FBA provides a framework for analyzing the transience of
      metabolism due to metabolic reprogramming and for obtaining insights for the
      design of metabolic networks.

PMID- 12202359
TI  - Electrostatic contributions to T4 lysozyme stability: solvent-exposed charges
      versus semi-buried salt bridges.
AB  - We carried our Poisson-Boltzmann (PB) calculations for the effects of charge
      reversal at five exposed sites (K16E, R119E, K135E, K147E, and R154E) and charge
      neutralization and proton titration of the H31-D70 semi-buried salt bridge on the
      stability of T4 lysozyme. Instead of the widely used solvent-exclusion (SE)
      surface, we used the van der Waals (vdW) surface as the boundary between the
      protein and solvent dielectrics (a protocol established in our earlier study on
      charge mutations in barnase). By including residual charge-charge interactions in
      the unfolded state, the five charge reversal mutations were found to have
      DeltaDeltaG(unfold) from -1.6 to 1.3 kcal/mol. This indicates that the variable
      effects of charge reversal observed by Matthews and co-workers are not
      unexpected. The H31N, D70N, and H31N/D70N mutations were found to destabilize the
      protein by 2.9, 1.3, and 1.6 kcal/mol, and the pK(a) values of H31 and D70 were
      shifted to 9.4 and 0.6, respectively. These results are in good accord with
      experimental data of Dahlquist and co-workers. In contrast, if the SE surface
      were used, the H31N/D70N mutant would be more stable than the wild-type protein
      by 1.3 kcal/mol. From these and additional results for 27 charge mutations on
      five other proteins, we conclude that 1) the popular view that electrostatic
      interactions are generally destabilizing may have been based on overestimated
      desolvation cost as a result of using the SE surface as the dielectric boundary;
      and 2) while solvent-exposed charges may not reliably contribute to protein
      stability, semi-buried salt bridges can provide significant stabilization.

PMID- 12202361
TI  - Establishing direction during chemotaxis in eukaryotic cells.
AB  - Several recent studies have demonstrated that eukaryotic cells, including
      amoeboid cells of Dictyostelium discoideum and neutrophils, respond to
      chemoattractants by translocation of PH-domain proteins to the cell membrane,
      where these proteins participate in the modulation of the cytoskeleton and relay
      of the signal. When the chemoattractant is released from a pipette, the
      localization is found predominantly on the proximal side of the cell. The
      recruitment of PH-domain proteins, particularly for Dictyostelium cells, occurs
      very rapidly (<2 s). Thus, the mechanism responsible for the first step in the
      directional sensing process of a cell must be able to establish an asymmetry on
      the same time scale. Here, we propose a simple mechanism in which a second
      messenger, generated by local activation of the membrane, diffuses through the
      interior of the cell, suppresses the activation of the back of the cell, and
      converts the temporal gradient into an initial cellular asymmetry. Numerical
      simulations show that such a mechanism is plausible. Available evidence suggests
      that the internal inhibitor may be cGMP, which accumulates within less than a
      second following treatment of cells with external cAMP.

PMID- 12202360
TI  - Continuum electrostatics fails to describe ion permeation in the gramicidin
      channel.
AB  - We investigate the validity of continuum electrostatics in the gramicidin A
      channel using a recently determined high-resolution structure. The potential and
      electric field acting on ions in and around the channel are computed by solving
      Poisson's equation. These are then used in Brownian dynamics simulations to
      obtain concentration profiles and the current passing through the channel. We
      show that regardless of the effective dielectric constant used for water in the
      channel or the channel protein, it is not possible to reproduce all the
      experimental data on gramicidin A; thus, continuum electrostatics cannot provide
      a valid framework for the description of ion dynamics in gramicidin channels.
      Using experimental data and molecular dynamics simulations as guides, we have
      constructed potential energy profiles that can satisfactorily describe the
      available physiological data. These profiles provide useful benchmarks for future
      potential of mean force calculations of permeating ions from molecular dynamics
      simulations of gramicidin A. They also offer a convenient starting point for
      studying structure-function relationships in modified gramicidin channels.

PMID- 12202362
TI  - New and corrected simulations of synaptic facilitation.

PMID- 12202363
TI  - Bridging implicit and explicit solvent approaches for membrane electrostatics.
AB  - Conformations of a zwitterionic bilayer were sampled from a molecular dynamics
      simulation and their electrostatic properties analyzed by solution of the Poisson
      equation. These traditionally implicit electrostatic calculations were performed
      in the presence of varying amounts of explicit solvent to assess the magnitude of
      error introduced by a uniform dielectric description of water surrounding the
      bilayer. It was observed that membrane dipole potential calculations in the
      presence of explicit water were significantly different than wholly implicit
      solvent calculations with the calculated dipole potential converging to a
      reasonable value when four or more hydration layers were included explicitly.

PMID- 12202364
TI  - Calculation of forces at focal adhesions from elastic substrate data: the effect
      of localized force and the need for regularization.
AB  - Forces exerted by stationary cells have been investigated on the level of single
      focal adhesions by combining elastic substrates, fluorescence labeling of focal
      adhesions, and the assumption of localized force when solving the inverse problem
      of linear elasticity theory. Data simulation confirms that the inverse problem is
      ill-posed in the presence of noise and shows that in general a regularization
      scheme is needed to arrive at a reliable force estimate. Spatial and force
      resolution are restricted by the smoothing action of the elastic kernel, depend
      on the details of the force and displacement patterns, and are estimated by data
      simulation. Corrections arising from the spatial distribution of force and from
      finite substrate size are treated in the framework of a force multipolar
      expansion. Our method is computationally cheap and could be used to study
      mechanical activity of cells in real time.

PMID- 12202365
TI  - Fluorescence resonance energy transfers measurements on cell surfaces via
      fluorescence polarization.
AB  - A method has been developed for the determination of the efficiency of
      fluorescence resonance energy transfer efficiency between moieties located on
      cell surfaces by performing individual cell fluorescence polarization (FP)
      measurements. The absolute value of energy transfer efficiency (E) is calculated
      on an individual cell basis. The examination of this methodology was carried out
      using model experiments on human T lymphocyte cells. The cells were labeled with
      fluorescein-conjugated Concanavalin A (ConA) as donor, or rhodamine-conjugated
      ConA as acceptor. The experiments and results clearly indicate that determination
      of E via FP measurements is possible, efficient, and more convenient than other
      methods.

PMID- 12202366
TI  - Dynamic behavior of rod photoreceptor disks.
AB  - Eukaryotic cells use membrane organelles, like the endoplasmic reticulum or the
      Golgi, to carry out different functions. Vertebrate rod photoreceptors use
      hundreds of membrane sacs (the disks) for the detection of light. We have used
      fluorescent tracers and single cell imaging to study the properties of rod
      photoreceptor disks. Labeling of intact rod photoreceptors with membrane markers
      and polar tracers revealed communication between intradiskal and extracellular
      space. Internalized tracers moved along the length of the rod outer segment,
      indicating communication between the disks as well. This communication involved
      the exchange of both membrane and aqueous phase and had a time constant in the
      order of minutes. The communication pathway uses approximately 2% of the
      available membrane disk area and does not allow the passage of molecules larger
      than 10 kDa. It was possible to load the intradiskal space with fluorescent
      Ca(2+) and pH dyes, which reported an intradiskal Ca(2+) concentration in the
      order of 1 microM and an acidic pH 6.5, both of them significantly different than
      intracellular and extracellular Ca(2+) concentrations and pH. The results suggest
      that the rod photoreceptor disks are not discrete, passive sacs but rather
      comprise an active cellular organelle. The communication between disks may be
      important for membrane remodeling as well as for providing access to the
      intradiskal space of the whole outer segment.

PMID- 12202367
TI  - Effects of volatile anesthetic on channel structure of gramicidin A.
AB  - Volatile anesthetic agent, 1-chloro-1,2,2-trifluorocyclobutane (F3), was found to
      alter gramicidin A channel function by enhancing Na(+) transport (. Biophys. J.
      77:739-746). Whether this functional change is associated with structural
      alternation is evaluated by circular dichroism and nuclear magnetic resonance
      spectroscopy. The circular dichroism and nuclear magnetic resonance results
      indicate that at low millimolar concentrations, 1-chloro-1,2,2
      trifluorocyclobutane causes minimal changes in gramicidin A channel structure in
      sodium dodecyl sulfate micelles. All hydrogen bonds between channel backbones are
      well maintained in the presence of 1-chloro-1,2,2-trifluorocyclobutane, and the
      channel structure is stable. The finding supports the notion that low affinity
      drugs such as volatile anesthetics and alcohols can cause significant changes in
      protein function without necessarily producing associated changes in protein
      structure. To understand the molecular mechanism of general anesthesia, it is
      important to recognize that in addition to structural changes, other protein
      properties, including dynamic characteristics of channel motions, may also be of
      functional significance.

PMID- 12202368
TI  - Regulation of nuclear pore complex conformation by IP(3) receptor activation.
AB  - In recent years, both the molecular architecture and functional dynamics of
      nuclear pore complexes (NPCs) have been revealed with increasing detail. These
      large, supramolecular assemblages of proteins form channels that span the nuclear
      envelope of cells, acting as crucial regulators of nuclear import and export.
      From the cytoplasmic face of the nuclear envelope, nuclear pore complexes exhibit
      an eightfold symmetric ring structure encompassing a central lumen. The lumen
      often appears occupied by an additional structure alternatively referred to as
      the central granule, nuclear transport complex, or nuclear plug. Previous studies
      have suggested that the central granule may play a role in mediating calcium
      dependent regulation of diffusion across the nuclear envelope for intermediate
      sized molecules (10-40 kDa). Using atomic force microscopy to measure the surface
      topography of chemically fixed Xenopus laevis oocyte nuclear envelopes, we
      present measurements of the relative position of the central granule within the
      NPC lumen under a variety of conditions known to modify nuclear Ca(2+) stores.
      These measurements reveal a large, approximately 9-nm displacement of the central
      granule toward the cytoplasmic face of the nuclear envelope under calcium
      depleting conditions. Additionally, activation of nuclear inositol triphosphate
      (IP(3)) receptors by the specific agonist, adenophostin A, results in a
      concentration-dependent displacement of central granule position with an EC(50)
      of ~1.2 nM. The displacement of the central granule within the NPC is observed on
      both the cytoplasmic and nucleoplasmic faces of the nuclear envelope. The
      displacement is blocked upon treatment with xestospongin C, a specific inhibitor
      of IP(3) receptor activation. These results extend previous models of NPC
      conformational dynamics linking central granule position to depletion of IP(3)
      sensitive nuclear envelope calcium stores.

PMID- 12202369
TI  - A specific tryptophan in the I-II linker is a key determinant of beta-subunit
      binding and modulation in Ca(V)2.3 calcium channels.
AB  - The ancillary beta subunits modulate the activation and inactivation properties
      of high-voltage activated (HVA) Ca(2+) channels in an isoform-specific manner.
      The beta subunits bind to a high-affinity interaction site, alpha-interaction
      domain (AID), located in the I-II linker of HVA alpha1 subunits. Nine residues in
      the AID motif are absolutely conserved in all HVA channels (QQxExxLxGYxxWIxxxE),
      but their contribution to beta-subunit binding and modulation remains to be
      established in Ca(V)2.3. Mutations of W386 to either A, G, Q, R, E, F, or Y in
      Ca(V)2.3 disrupted [(35)S]beta3-subunit overlay binding to glutathione S
      transferase fusion proteins containing the mutated I-II linker, whereas mutations
      (single or multiple) of nonconserved residues did not affect the protein-protein
      interaction with beta3. The tryptophan residue at position 386 appears to be an
      essential determinant as substitutions with hydrophobic (A and G), hydrophilic
      (Q, R, and E), or aromatic (F and Y) residues yielded the same results. beta
      Subunit modulation of W386 (A, G, Q, R, E, F, and Y) and Y383 (A and S) mutants
      was investigated after heterologous expression in Xenopus oocytes. All mutant
      channels expressed large inward Ba(2+) currents with typical current-voltage
      properties. Nonetheless, the typical hallmarks of beta-subunit modulation, namely
      the increase in peak currents, the hyperpolarization of peak voltages, and the
      modulation of the kinetics and voltage dependence of inactivation, were
      eliminated in all W386 mutants, although they were preserved in part in Y383 (A
      and S) mutants. Altogether these results suggest that W386 is critical for beta
      subunit binding and modulation of HVA Ca(2+) channels.

PMID- 12202370
TI  - Asymmetrical membranes and surface tension.
AB  - The (31)P-nuclear magnetic resonance chemical shift of phosphatidic acid in a
      membrane is sensitive to the lipid head group packing and can report
      qualitatively on membrane lateral compression near the aqueous interface. We have
      used high-resolution (31)P-nuclear magnetic resonance to evaluate the lateral
      compression on each side of asymmetrical lipid vesicles. When
      monooleoylphosphatidylcholine was added to the external monolayer of sonicated
      vesicles containing dioleoylphosphatidylcholine and dioleoylphosphatidic acid,
      the variation of (31)P chemical shift of phosphatidic acid indicated a lateral
      compression in the external monolayer. Simultaneously, a slight dilation was
      observed in the inner monolayer. In large unilamellar vesicles on the other hand
      the lateral pressure increased in both monolayers after asymmetrical insertion of
      monooleoylphosphatidylcholine. This can be explained by assuming that when
      monooleoylphosphatidylcholine is added to large unilamellar vesicles, the
      membrane bends until the strain is the same in both monolayers. In the case of
      sonicated vesicles, a change of curvature is not possible, and therefore
      differential packing in the two layers remains. We infer that a variation of
      lipid asymmetry by generating a lateral strain in the membrane can be a
      physiological way of modulating the conformation of membrane proteins.

PMID- 12202371
TI  - Dynamic light scattering study of calmodulin-target peptide complexes.
AB  - Dynamic light scattering (DLS) has been used to assess the influence of eleven
      different synthetic peptides, comprising the calmodulin (CaM)-binding domains of
      various CaM-binding proteins, on the structure of apo-CaM (calcium-free) and
      Ca(2+)-CaM. Peptides that bind CaM in a 1:1 and 2:1 peptide-to-protein ratio were
      studied, as were solutions of CaM bound simultaneously to two different peptides.
      DLS was also used to investigate the effect of Ca(2+) on the N- and C-terminal
      CaM fragments TR1C and TR2C, and to determine whether the two lobes of CaM
      interact in solution. The results obtained in this study were comparable to
      similar solution studies performed for some of these peptides using small-angle x
      ray scattering. The addition of Ca(2+) to apo-CaM increased the hydrodynamic
      radius from 2.5 to 3.0 nm. The peptides studied induced a collapse of the
      elongated Ca(2+)-CaM structure to a more globular form, decreasing its
      hydrodynamic radius by an average of 25%. None of the peptides had an effect on
      the conformation of apo-CaM, indicating that either most of the peptides did not
      interact with apo-CaM, or if bound, they did not cause a large conformational
      change. The hydrodynamic radii of TR1C and TR2C CaM fragments were not
      significantly affected by the addition of Ca(2+). The addition of a target
      peptide and Ca(2+) to the two fragments of CaM, suggest that a globular complex
      is forming, as has been seen in nuclear magnetic resonance solution studies. This
      work demonstrates that dynamic light scattering is an inexpensive and efficient
      technique for assessing large-scale conformational changes that take place in
      calmodulin and related proteins upon binding of Ca(2+) ions and peptides, and
      provides a qualitative picture of how this occurs. This work also illustrates
      that DLS provides a rapid screening method for identifying new CaM targets.

PMID- 12202372
TI  - A solid-state NMR study of phospholipid-cholesterol interactions: sphingomyelin
      cholesterol binary systems.
AB  - We used solid-state NMR techniques to probe the interactions of cholesterol
      (Chol) with bovine brain sphingomyelin (SM) and for comparison of the
      interactions of Chol with dipalmitoylphosphatidylcholine (DPPC), which has a
      similar gel-to-liquid crystalline transition temperature. (1)H-, (31)P-, and
      (13)C-MASNMR yielded high-resolution spectra from multilamellar dispersions of
      unlabeled brain SM and Chol for analysis of chemical shifts and linewidths. In
      addition, (2)H-NMR spectra of oriented lipid membranes with specific deuterium
      labels gave information about membrane ordering and mobility. Chol disrupted the
      gel-phase of pure SM and increased acyl chain ordering in the liquid crystalline
      phase. As inferred from (13)C chemical shifts, the boundaries between the ordered
      and disordered liquid crystalline phases (L and L) were similar for SM and DPPC.
      The solubility limit of Chol in SM was ~50 mol %, the same value as previously
      reported for DPPC membranes. We found no evidence for specific H-bonding between
      Chol and the amide group of SM. The order parameters of a probe molecule, d31-sn1
      DPPC, in SM were slightly higher than in DPPC for all carbons except the terminal
      groups at 30 mol % but were not significantly different at 5 and 60 mol % Chol.
      These studies show a general similarity with some subtle differences in the way
      Chol interacts with DPPC and SM. In the environment of a typical biomembrane, the
      higher proportion of saturated fatty acyl chains in SM compared to other
      phospholipids may be the most significant factor influencing interactions with
      Chol.

PMID- 12202373
TI  - Geometry and intrinsic tilt of a tryptophan-anchored transmembrane alpha-helix
      determined by (2)H NMR.
AB  - We used solid-state deuterium NMR spectroscopy and an approach involving
      geometric analysis of labeled alanines (GALA method) to examine the structure and
      orientation of a designed synthetic hydrophobic, membrane-spanning alpha-helical
      peptide in phosphatidylcholine (PC) bilayers. The 19-amino-acid peptide consists
      of an alternating leucine and alanine core, flanked by tryptophans that serve as
      interfacial anchors: acetyl-GWW(LA)(6)LWWA-ethanolamine (WALP19). A single
      deuterium-labeled alanine was introduced at different positions within the
      peptide. Peptides were incorporated in oriented bilayers of dilauroyl- (di-C12:0
      ), dimyristoyl- (di-C14:0-), or dioleoyl- (di-C18:1(c)-) phosphatidylcholine. The
      NMR data fit well to a WALP19 orientation characterized by a distinctly nonzero
      tilt, approximately 4 degrees from the membrane normal, and rapid reorientation
      about the membrane normal in all three lipids. Although the orientation of WALP19
      varies slightly in the different lipids, hydrophobic mismatch does not seem to be
      the dominant factor causing the tilt. We suggest rather that the peptide itself
      has an inherently preferred tilted orientation, possibly related to peptide
      surface characteristics or the disposition of tryptophan indole anchors relative
      to the lipids, the peptide backbone, and the membrane/water interface.
      Additionally, the data allow us to define more precisely the local alanine
      geometry in this membrane-spanning alpha-helix.

PMID- 12202374
TI  - Lateral diffusion in substrate-supported lipid monolayers as a function of
      ambient relative humidity.
AB  - We analyzed the influence of water activity on the lateral self-diffusion of
      supported phospholipid monolayers. Lipid monolayer membranes were supported by
      polysaccharide cushions (chitosan and agarose), or glass. A simple diffusion
      model was derived, based on activated diffusion with an activation energy, E(a),
      which depends on the hydration state of the lipid headgroup. A crucial assumption
      of the derived model is that E(a) can be calculated assuming an exponential decay
      of the humidity-dependent disjoining pressure in the monolayer/substrate
      interface with respect to the equilibrium separation distance. A plot of ln(D)
      against ln(p(0)/p), where D is the measured diffusion coefficient and p(0) and p
      are the partial water pressures at saturation and at a particular relative
      humidity, respectively, was observed to be linear in all cases (i.e., for
      differing lipids, lateral monolayer pressures, temperatures, and substrates), in
      accordance with the above-mentioned diffusion model. No indications for humidity
      induced first-order phase transitions in the supported phospholipid monolayers
      were found. Many biological processes such as vesicle fusion and recognition
      processes involve dehydration/hydration cycles, and it can be expected that the
      water activity significantly affects the kinetics of these processes in a manner
      similar to that examined in the present work.

PMID- 12202375
TI  - Molecular dynamics simulation of the evolution of hydrophobic defects in one
      monolayer of a phosphatidylcholine bilayer: relevance for membrane fusion
      mechanisms.
AB  - The spontaneous formation of the phospholipid bilayer underlies the permeability
      barrier function of the biological membrane. Tears or defects that expose water
      to the acyl chains are spontaneously healed by lipid lateral diffusion. However,
      mechanical barriers, e.g., protein aggregates held in place, could sustain
      hydrophobic defects. Such defects have been postulated to occur in processes such
      as membrane fusion. This gives rise to a new question in bilayer structure: What
      do the lipids do in the absence of lipid lateral diffusion to minimize the free
      energy of a hydrophobic defect? As a first step to understand this rather
      fundamental question about bilayer structure, we performed molecular dynamic
      simulations of up to 10 ns of a planar bilayer from which lipids have been
      deleted randomly from one monolayer. In one set of simulations, approximately one
      half of the lipids in the defect monolayer were restrained to form a mechanical
      barrier. In the second set, lipids were free to diffuse around. The question was
      simply whether the defects caused by removing a lipid would aggregate together,
      forming a large hydrophobic cavity, or whether the membrane would adjust in
      another way. When there are no mechanical barriers, the lipids in the defect
      monolayer simply spread out and thin with little effect on the other intact
      monolayer. In the presence of a mechanical barrier, the behavior of the lipids
      depends on the size of the defect. When 3 of 64 lipids are removed, the remaining
      lipids adjust the lower one-half of their chains, but the headgroup structure
      changes little and the intact monolayer is unaffected. When 6 to 12 lipids are
      removed, the defect monolayer thins, lipid disorder increases, and lipids from
      the intact monolayer move toward the defect monolayer. Whereas this is a highly
      simplified model of a fusion site, this engagement of the intact monolayer into
      the fusion defect is strikingly consistent with recent results for influenza
      hemagglutinin mediated fusion.

PMID- 12202376
TI  - Physical and photophysical characterization of a BODIPY phosphatidylcholine as a
      membrane probe.
AB  - Lipids containing the dimethyl BODIPY fluorophore are used in cell biology
      because their fluorescence properties change with fluorophore concentration (C.
      S. Chen, O. C. Martin, and R. E. Pagano. 1997. Biophys J. 72:37-50). The
      miscibility and steady-state fluorescence behavior of one such lipid, 1-palmitoyl
      2-(4,4-difluoro-5,7-dimethyl-4-bora-3a,4a-diaza-s-indacene-3-pentanoyl)-sn
      glycero-3-phosphocholine (PBPC), have been characterized in mixtures with 1
      stearoyl-2-oleoyl-sn-glycero-3-phosphocholine (SOPC). PBPC packs similarly to
      phosphatidylcholines having a cis-unsaturated acyl chain and mixes nearly ideally
      with SOPC, apparently without fluorophore-fluorophore aggregation. Increasing
      PBPC mole fraction from 0.0 to 1.0 in SOPC membranes changes the emission
      characteristics of the probe in a continuous manner. Analysis of these changes
      shows that emission from the excited dimethyl BODIPY monomer self quenches with a
      critical radius of 25.9 A. Fluorophores sufficiently close (< or =13.7 A) at the
      time of excitation can form an excited dimer, emission from which depends
      strongly on total lipid packing density. Overall, the data show that PBPC is a
      reasonable physical substitute for other phosphatidylcholines in fluid membranes.
      Knowledge of PBPC fluorescence in lipid monolayers has been exploited to
      determine the two-dimensional concentration of SOPC in unilamellar, bilayer
      membranes.

PMID- 12202377
TI  - Rapid transbilayer movement of the fluorescent sterol dehydroergosterol in lipid
      membranes.
AB  - This study establishes a new assay for measuring the transbilayer movement of
      dehydroergosterol (DHE) in lipid membranes. The assay is based on the rapid
      extraction of DHE by methyl-beta-cyclodextrin (M-CD) from liposomes. The
      concentration of DHE in the liposomal membrane was measured by using fluorescence
      resonance energy transfer (FRET) from DHE to dansyl-phosphatidylethanolamine,
      which is not extracted from liposomes by M-CD. The method was applied to small
      (SUV) and large (LUV) unilamellar vesicles of different compositions and at
      various temperatures. From the kinetics of FRET changes upon extraction of DHE
      from membranes, rates of M-CD mediated extraction and flip-flop of DHE could be
      deduced and were found to be dependent on the physical state of the lipid phase.
      For egg phosphocholine and 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine in
      the liquid-crystalline state, halftimes of extraction and transbilayer movement
      were <5 s and approximately 20-50 s, respectively, at 10 degrees C. For 1,2
      dimyristoyl-sn-glycero-3-phosphocholine-SUV being in the gel state at 10 degrees
      C, the respective halftimes were 28 s and 5-8 min. Surprisingly, DHE could not be
      extracted from LUV consisting of 1,2-dimyristoyl-sn-glycero-3-phosphocholine.
      This might be an indication of specific interactions between DHE molecules in
      membranes depending on the phospholipid composition of the membrane.

PMID- 12202378
TI  - Lactosylceramide: effect of acyl chain structure on phase behavior and molecular
      packing.
AB  - Lactosylceramide (LacCer) is a pivotal intermediate in the metabolism of higher
      gangliosides, localizes to sphingolipid-sterol "rafts," and has been implicated
      in cellular signaling. To provide a fundamental characterization of LacCer phase
      behavior and intermolecular packing, LacCer containing different saturated (16:0,
      18:0, 24:0) or monounsaturated (18:1(Delta9), 24:1(Delta15)) acyl chains were
      synthesized and studied by differential scanning calorimetry and Langmuir film
      balance approaches. Compared to related sphingoid- and glycerol-based lipids,
      LacCers containing saturated acyl chains display relatively high thermotropic and
      pressure-induced transitions. LacCer monolayer films are less elastic in an in
      plane sense than sphingomyelin films, but are somewhat more elastic than
      galactosylceramide films. Together, these findings indicate that the disaccharide
      headgroup only marginally disrupts gel phase packing and orients more
      perpendicular than parallel to the interface. This contrasts the reported
      behavior of digalactosyldiglycerides with saturated acyl chains. Introducing
      single cis double bonds into the LacCer acyl chains dramatically lowers the high
      thermotropic and pressure-induced transitions. Greater reductions occur when cis
      double bonds are located near the middle of the acyl chains. The results are
      discussed in terms of how an extended disaccharide headgroup can enhance
      interactions among naturally abundant LacCers with saturated acyl chains.

PMID- 12202379
TI  - Thermodynamics of sodium dodecyl sulfate partitioning into lipid membranes.
AB  - The partition equilibria of sodium dodecyl sulfate (SDS) and lithium dodecyl
      sulfate between water and bilayer membranes were investigated with isothermal
      titration calorimetry and spectroscopic methods (light scattering, (31)P-nuclear
      magnetic resonance) in the temperature range of 28 degrees C to 56 degrees C. The
      partitioning of the dodecyl sulfate anion (DS(-)) into the bilayer membrane is
      energetically favored by an exothermic partition enthalpy of Delta H(O)(D) = -6.0
      kcal/mol at 28 degrees C. This is in contrast to nonionic detergents where Delta
      H(O)(D) is usually positive. The partition enthalpy decreases linearly with
      increasing temperature and the molar heat capacity is Delta C(O)(P) = -50 +/- 3
      cal mol(-1) K(-1). The partition isotherm is nonlinear if the bound detergent is
      plotted versus the free detergent concentration in bulk solution. This is caused
      by the electrostatic repulsion between the DS(-) ions inserted into the membrane
      and those free in solution near the membrane surface. The surface concentration
      of DS(-) immediately above the plane of binding was hence calculated with the
      Gouy-Chapman theory, and a strictly linear relationship was obtained between the
      surface concentration and the extent of DS(-) partitioning. The surface partition
      constant K describes the chemical equilibrium in the absence of electrostatic
      effects. For the SDS-membrane equilibrium K was found to be 1.2 x 10(4) M(-1) to
      6 x 10(4) M(-1) for the various systems and conditions investigated, very similar
      to data available for nonionic detergents of the same chain length. The membrane
      micelle phase diagram was also studied. Complete membrane solubilization requires
      a ratio of 2.2 mol SDS bound per mole of total lipid at 56 degrees C. The
      corresponding equilibrium concentration of SDS free in solution is C (sat)(D,F)
      approximately 1.7 mM and is slightly below the critical micelles concentration
      (CMC) = 2.1 mM (at 56 degrees C and 0.11 M buffer). Membrane saturation occurs at
      approximately 0.3 mol SDS per mol lipid and the equilibrium SDS concentration is
      C (sat)(D,F)approximately equal 2.2 mM +/- 0.6 mM. SDS translocation across the
      bilayer is slow at ambient temperature but increases at high temperatures.

PMID- 12202380
TI  - Comparison of the dynamics of the primary events of bacteriorhodopsin in its
      trimeric and monomeric states.
AB  - In this paper, femtosecond pump-probe spectroscopy in the visible region of the
      spectrum has been used to examine the ultrafast dynamics of the retinal excited
      state in both the native trimeric state and the monomeric state of
      bacteriorhodopsin (bR). It is found that the excited state lifetime (probed at
      490 nm) increases only slightly upon the monomerization of bR. No significant
      kinetic difference is observed in the recovery process of the bR ground state
      probed at 570 nm nor in the fluorescent state observed at 850 nm. However, an
      increase in the relative amplitude of the slow component of bR excited state
      decay is observed in the monomer, which is due to the increase in the
      concentration of the 13-cis retinal isomer in the ground state of the light
      adapted bR monomer. Our data indicate that when the protein packing around the
      retinal is changed upon bR monomerization, there is only a subtle change in the
      retinal potential surface, which is dependent on the charge distribution and the
      dipoles within the retinal-binding cavity. In addition, our results show that 40%
      of the excited state bR molecules return to the ground state on three different
      time scales: one-half-picosecond component during the relaxation of the excited
      state and the formation of the J intermediate, a 3-ps component as the J changes
      to the K intermediate where retinal photoisomerization occurs, and a
      subnanosecond component during the photocycle.

PMID- 12202381
TI  - Structural change of site-directed mutants of PYP: new dynamics during pR state.
AB  - The energetics, protein dynamics, and diffusion coefficients of three mutants of
      photoactive yellow protein, R52Q, P68A, and W119G, were studied by the transient
      grating and pulsed laser-induced photoacoustic method. We observed a new dynamics
      with a lifetime of approximately 1 micro s in the transient grating signal, which
      is silent by the light absorption technique. This fact indicates that, after the
      structure change around the chromophore is completed (pR(1)), the protein part
      located far from the chromophore is still moving to finally create another pR
      (pR(2)) species, which can transform to the next intermediate, pB. Although the
      kinetics of pR(2)-->pB-->pG are very different depending on the mutants, the
      enthalpies of the first long-lived (in micro seconds, 100-micro s range)
      intermediate species (pR(2)) are similar and very high for all mutants. The
      diffusion coefficients of the parent (pG) and pB species of the mutants are also
      similar to that of the wild-type photoactive yellow protein. From the temperature
      dependence of the volume change, the difference in the thermal expansion
      coefficients taken as indicator of the flexibility of the structure between pG
      and pR(2) is measured. They are also similar to that of the wild-type photoactive
      yellow protein. These results suggest that the protein structures of pR(2) and pB
      in these mutants are globally different from that of pG, and this structural
      change is not altered so much by the single amino acid residue mutation. This is
      consistent with the partially unfolded nature of these intermediate species. On
      the other hand, the volume changes during pR(1)-->pR(2) are sensitive to the
      mutations, which may suggest that the volume change reflects a rather local
      character of the structure, such as the chromophore-protein interaction.

PMID- 12202382
TI  - A model for water motion in crystals of lysozyme based on an incoherent
      quasielastic neutron-scattering study.
AB  - This paper reports an incoherent quasielastic neutron scattering study of the
      single particle, diffusive motions of water molecules surrounding a globular
      protein, the hen egg-white lysozyme. For the first time such an analysis has been
      done on protein crystals. It can thus be directly related and compared with a
      recent structural study of the same sample. The measurement temperature ranged
      from 100 to 300 K, but focus was on the room temperature analysis. The very good
      agreement between the structural and dynamical studies suggested a model for the
      dynamics of water in triclinic crystals of lysozyme in the time range
      approximately 330 ps and at 300 K. Herein, the dynamics of all water molecules is
      affected by the presence of the protein, and the water molecules can be divided
      into two populations. The first mainly corresponds to the first hydration shell,
      in which water molecules reorient themselves fivefold to 10-fold slower than in
      bulk solvent, and diffuse by jumps from hydration site to hydration site. The
      long-range diffusion coefficient is five to sixfold less than for bulk solvent.
      The second group corresponds to water molecules further away from the surface of
      the protein, in a second incomplete hydration layer, confined between hydrated
      macromolecules. Within the time scale probed they undergo a translational
      diffusion with a self-diffusion coefficient reduced approximately 50-fold
      compared with bulk solvent. As protein crystals have a highly crowded arrangement
      close to the packing of macromolecules in cells, our conclusion can be discussed
      with respect to solvent behavior in intracellular media: as the mobility is
      highest next to the surface, it suggests that under some crowding conditions, a
      two-dimensional motion for the transport of metabolites can be dominant.

PMID- 12202383
TI  - Time-resolved long-lived infrared emission from bacteriorhodopsin during its
      photocycle.
AB  - The infrared emission observed below 2000 cm(-1) upon exciting retinal in
      bacteriorhodopsin (bR) is found to have a rise time in the submicrosecond time
      regime and to relax with two exponential components on the submillisecond to
      millisecond time scale. These time scales, together with the assignment of this
      emission to hot vibrations from the all-trans retinal (in bR) and the 13-cis
      retinal (in the K intermediate), support the recent assignment of the J
      intermediate as an electronically excited species (Atkinson et al., J. Phys.
      Chem. A. 104:4130-4139, 2000) rather than a vibrationally hot K intermediate. A
      discussion of these time scales of the observed infrared emission is given in
      terms of the competition between radiative and nonradiative relaxation processes
      of the vibrational states involved.

PMID- 12202384
TI  - Relationship between ion pair geometries and electrostatic strengths in proteins.
AB  - The electrostatic free energy contribution of an ion pair in a protein depends on
      two factors, geometrical orientation of the side-chain charged groups with
      respect to each other and the structural context of the ion pair in the protein.
      Conformers in NMR ensembles enable studies of the relationship between geometry
      and electrostatic strengths of ion pairs, because the protein structural contexts
      are highly similar across different conformers. We have studied this relationship
      using a dataset of 22 unique ion pairs in 14 NMR conformer ensembles for 11
      nonhomologous proteins. In different NMR conformers, the ion pairs are classified
      as salt bridges, nitrogen-oxygen (N-O) bridges and longer-range ion pairs on the
      basis of geometrical criteria. In salt bridges, centroids of the side-chain
      charged groups and at least a pair of side-chain nitrogen and oxygen atoms of the
      ion-pairing residues are within a 4 A distance. In N-O bridges, at least a pair
      of the side-chain nitrogen and oxygen atoms of the ion-pairing residues are
      within 4 A distance, but the distance between the side-chain charged group
      centroids is greater than 4 A. In the longer-range ion pairs, the side-chain
      charged group centroids as well as the side-chain nitrogen and oxygen atoms are
      more than 4 A apart. Continuum electrostatic calculations indicate that most of
      the ion pairs have stabilizing electrostatic contributions when their side-chain
      charged group centroids are within 5 A distance. Hence, most (approximately 92%)
      of the salt bridges and a majority (68%) of the N-O bridges are stabilizing. Most
      (approximately 89%) of the destabilizing ion pairs are the longer-range ion
      pairs. In the NMR conformer ensembles, the electrostatic interaction between side
      chain charged groups of the ion-pairing residues is the strongest for salt
      bridges, considerably weaker for N-O bridges, and the weakest for longer-range
      ion pairs. These results suggest empirical rules for stabilizing electrostatic
      interactions in proteins.

PMID- 12202385
TI  - Cooperativity and specificity of association of a designed transmembrane peptide.
AB  - Thermodynamics studies aimed at quantitatively characterizing free energy effects
      of amino acid substitutions are not restricted to two state systems, but do
      require knowing the number of states involved in the equilibrium under
      consideration. Using analytical ultracentrifugation and NMR methods, we show here
      that a membrane-soluble peptide, MS1, designed by modifying the sequence of the
      water-soluble coiled-coil GCN4-P1, exhibits a reversible monomer-dimer-trimer
      association in detergent micelles with a greater degree of cooperativity in C14
      betaine than in dodecyl phosphocholine detergents.

PMID- 12202386
TI  - Efficient generation of feasible pathways for protein conformational transitions.
AB  - We develop a computationally efficient method to simulate the transition of a
      protein between two conformations. Our method is based on a coarse-grained
      elastic network model in which distances between spatially proximal amino acids
      are interpolated between the values specified by the two end conformations. The
      computational speed of this method depends strongly on the choice of cutoff
      distance used to define interactions as measured by the density of entries of the
      constant linking/contact matrix. To circumvent this problem we introduce the
      concept of using a cutoff based on a maximum number of nearest neighbors. This
      generates linking matrices that are both sparse and uniform, hence allowing for
      efficient computations that are independent of the arbitrariness of cutoff
      distance choices. Simulation results demonstrate that the method developed here
      reliably generates feasible intermediate conformations, because our method
      observes steric constraints and produces monotonic changes in virtual bond and
      torsion angles. Applications are readily made to large proteins, and we
      demonstrate our method on lactate dehydrogenase, citrate synthase, and
      lactoferrin. We also illustrate how this framework can be used to complement
      experimental techniques that partially observe protein motions.

PMID- 12202387
TI  - Dynamic fluorescence anisotropy imaging microscopy in the frequency domain
      (rFLIM).
AB  - We describe a novel variant of fluorescence lifetime imaging microscopy (FLIM),
      denoted anisotropy-FLIM or rFLIM, which enables the wide-field measurement of the
      anisotropy decay of fluorophores on a pixel-by-pixel basis. We adapted existing
      frequency-domain FLIM technology for rFLIM by introducing linear polarizers in
      the excitation and emission paths. The phase delay and intensity ratios (AC and
      DC) between the polarized components of the fluorescence signal are recorded,
      leading to estimations of rotational correlation times and limiting anisotropies.
      Theory is developed that allows all the parameters of the hindered rotator model
      to be extracted from measurements carried out at a single modulation frequency.
      Two-dimensional image detection with a sensitive CCD camera provides wide-field
      imaging of dynamic depolarization with parallel interrogation of different
      compartments of a complex biological structure such as a cell. The concepts and
      technique of rFLIM are illustrated with a fluorophore-solvent (fluorescein
      glycerol) system as a model for isotropic rotational dynamics and with bacteria
      expressing enhanced green fluorescent protein (EGFP) exhibiting depolarization
      due to homotransfer of electronic excitation energy (emFRET). The frequency
      domain formalism was extended to cover the phenomenon of emFRET and yielded data
      consistent with a concentration depolarization mechanism resulting from the high
      intracellular concentration of EGFP. These investigations establish rFLIM as a
      powerful tool for cellular imaging based on rotational dynamics and molecular
      proximity.

PMID- 12202388
TI  - Diffusion and convection in collagen gels: implications for transport in the
      tumor interstitium.
AB  - Diffusion coefficients of tracer molecules in collagen type I gels prepared from
      0-4.5% w/v solutions were measured by fluorescence recovery after photobleaching.
      When adjusted to account for in vivo tortuosity, diffusion coefficients in gels
      matched previous measurements in four human tumor xenografts with equivalent
      collagen concentrations. In contrast, hyaluronan solutions hindered diffusion to
      a lesser extent when prepared at concentrations equivalent to those reported in
      these tumors. Collagen permeability, determined from flow through gels under
      hydrostatic pressure, was compared with predictions obtained from application of
      the Brinkman effective medium model to diffusion data. Permeability predictions
      matched experimental results at low concentrations, but underestimated measured
      values at high concentrations. Permeability measurements in gels did not match
      previous measurements in tumors. Visualization of gels by transmission electron
      microscopy and light microscopy revealed networks of long collagen fibers at
      lower concentrations along with shorter fibers at high concentrations. Negligible
      assembly was detected in collagen solutions pregelation. However, diffusion was
      similarly hindered in pre and postgelation samples. Comparison of diffusion and
      convection data in these gels and tumors suggests that collagen may obstruct
      diffusion more than convection in tumors. These findings have significant
      implications for drug delivery in tumors and for tissue engineering applications.

PMID- 12202389
TI  - Heterogeneity and persistence length in human ocular mucins.
AB  - Atomic force microscopy (AFM) has been used to investigate the heterogeneity and
      flexibility of human ocular mucins and their subunits. We have paid particular
      attention, in terms of theory and experiment, to the problem of inducing the
      polymers to assume equilibrium conformations at a surface. Mucins deposited from
      a buffer containing Ni(2+) ions adopt extended conformations on mica akin to
      those observed for DNA under similar conditions. The heterogeneity of the
      intracellular native mucins is evident from a histogram of contour lengths,
      reflecting, in part, the diversity of mucin gene products expressed. Reduction of
      the native mucin with dithiothreitol, thereby breaking the S==S bonds between
      cysteine residues, causes a marked reduction in polymer length. These results
      reflect the modes of transport and assembly of newly synthesized mucins in vivo.
      By modifying the worm-like chain model for applicability to two dimensions, we
      have confirmed that under the conditions employed mucin adsorbs to mica in an
      equilibrated conformation. The determined persistence length of the native mucin,
      36 nm, is consistent with that of an extended, flexible polymer; such
      characteristics will influence the properties of the gels formed in vivo.

PMID- 12202390
TI  - Two-photon fluorescence coincidence analysis: rapid measurements of enzyme
      kinetics.
AB  - Dual-color fluorescence cross-correlation analysis is a powerful tool for probing
      interactions of different fluorescently labeled molecules in aqueous solution.
      The concept is the selective observation of coordinated spontaneous fluctuations
      in two separate detection channels that unambiguously reflect the existence of
      physical or chemical linkages among the different fluorescent species. It has
      previously been shown that the evaluation of cross-correlation amplitudes, i.e.,
      coincidence factors, is sufficient to extract essential information about the
      kinetics of formation or cleavage of chemical or physical bonds. Confocal
      fluorescence coincidence analysis (CFCA) (Winkler et al., Proc. Natl. Acad. Sci.
      U.S.A. 96:1375-1378, 1999) emphasizes short analysis times and simplified data
      evaluation and is thus particularly useful for screening applications or
      measurements on live cells where small illumination doses need to be applied. The
      recent use of two-photon fluorescence excitation has simplified dual- or
      multicolor measurements by enabling the simultaneous excitation of largely
      different dye molecules by a single infra-red laser line (Heinze et al., Proc.
      Natl. Acad. Sci. U.S.A. 97:10377-10382, 2000). It is demonstrated here that a
      combination of CFCA with two-photon excitation allows for minimization of
      analysis times for multicomponent systems down to some hundreds of milliseconds,
      while preserving all known advantages of two-photon excitation. By introducing
      crucial measurement parameters, experimental limits for the reduction of sampling
      times are discussed for the special case of distinguishing positive from negative
      samples in an endonucleolytic cleavage assay.

PMID- 12202391
TI  - Two-photon fluorescence lifetime imaging of the skin stratum corneum pH gradient.
AB  - Two-photon fluorescence lifetime imaging is used to identify microdomains (1-25
      microm) of two distinct pH values within the uppermost layer of the epidermis
      (stratum corneum). The fluorophore used is 2',7'-bis-(2-carboxyethyl)-5-(and-6)
      carboxyfluorescein (BCECF), whose lifetime tau (pH 4.5, tau = 2.75 ns; pH 8.5,
      tau = 3.90 ns) is pH dependent over the pH range of the stratum corneum (pH 4.5
      to pH 7.2). Hairless mice (SKH1-hrBR) are used as a model for human skin. Images
      (< or =50 microm x 50 microm) are acquired every 1.7 microm from the stratum
      corneum surface to the first viable layer (stratum granulosum). Acidic
      microdomains (average pH 6.0) of variable size (~1 microm in diameter with
      variable length) are detected within the extracellular matrix of the stratum
      corneum, whereas the intracellular space of the corneocytes in mid-stratum
      corneum (25 microm diameter) approaches neutrality (average pH 7.0). The surface
      is acidic. The average pH of the stratum corneum increases with depth because of
      a decrease in the ratio of acidic to neutral regions within the stratum corneum.
      The data definitively show that the stratum corneum acid mantle results from the
      presence of aqueous acidic pockets within the lipid-rich extracellular matrix.

PMID- 12202392
TI  - Calcium-induced alterations in mitochondrial morphology quantified in situ with
      optical scatter imaging.
AB  - Optical scatter imaging (OSI), a technique we developed recently, was used to
      measure the ratio of wide-to-narrow angle scatter (OSIR) within endothelial cells
      subjected to calcium overload (1.6 mM) after permeabilization by ionomycin.
      Within a few minutes of calcium overload, the mitochondria, which started as
      elongated organelles, rounded up into spherically shaped particles. This change
      in morphology was accompanied by a statistically significant 14% increase in OSIR
      in the cells' cytoplasm. Mitochondrial rounding and OSIR increase were suppressed
      by cyclosporin A (25 microM), implying that the observed geometrical and
      scattering changes were directly attributable to the mitochondrial permeability
      transition. The angular scattering properties of a long mitochondrion rounding up
      were approximated by numerical simulations of light scatter from an ellipsoid
      rounding up into a sphere. The simulations predicted a relative increase in OSIR
      comparable to that measured experimentally for the case where the shape
      transition takes place with little or no volume increase. The simulations also
      suggested that mitochondrial refractive index changes could not account for the
      OSIR changes observed. Our data show that changes in OSIR correlate with
      mitochondrial morphology change in situ. OSI provides a new tool for subcellular
      imaging and complements other microscopy methods, such as fluorescence.

PMID- 12202393
TI  - Spectroscopy on individual light-harvesting 1 complexes of Rhodopseudomonas
      acidophila.
AB  - In this paper the fluorescence-excitation spectra of individual LH1-RC complexes
      (Rhodopseudomonas acidophila) at 1.2 K are presented. All spectra show a limited
      number of broad bands with a characteristic polarization behavior, indicating
      that the excitations are delocalized over a large number of pigments. A
      significant variation in the number of bands, their bandwidths, and polarization
      behavior is observed. Only 30% of the spectra carry a clear signature of
      delocalized excited states of a circular structure of the pigments. The large
      spectral variety suggests that besides site heterogeneity also structural
      heterogeneity determines the optical spectrum of the individual LH1-RC complexes.
      Further research should reveal if such heterogeneity is a native property of the
      complex or induced during the experimental procedures.

PMID- 12202394
TI  - Molecular organization of amyloid protofilament-like assembly of betabellin 15D:
      helical array of beta-sandwiches.
AB  - Betabellin is a 32-residue peptide engineered to fold into a four-stranded
      antiparallel beta-sheet protein. Upon air oxidation, the betabellin peptides can
      fold and assemble into a disulfide-bridged homodimer, or beta-sandwich, of 64
      residues. Recent biophysical and ultrastructural studies indicate that betabellin
      15D (B15D) (a homodimer of HSLTAKIpkLTFSIAphTYTCAVpkYTAKVSH, where p = DPro, k =
      DLys, and h = DHis) forms unbranched, 35-A wide assemblies that resemble the
      protofilaments of amyloid fibers. In the present study, we have analyzed in
      detail the X-ray diffraction patterns of B15D prepared from acetonitrile. The
      fiber diffraction analysis indicated that the B15D fibril was composed of a
      double helix defined by the selection rule l = n + 7m (where l is even, and n and
      m are any integers), and having a 199-A period and pitch, 28-A rise per unit, and
      10-A radius. This helical model is equivalent to a reverse-handed, single helix
      with half the period and defined by the selection rule l = -3n + 7m (where l is
      any integer). The asymmetric unit is the single B15D beta-sandwich molecule.
      These results suggest that the betabellin assembly that models the protofilaments
      of amyloid fibers is made up of discrete subunits on a helical array. Multiple
      intersheet hydrogen bonds in the axial direction and intersandwich polar
      interactions in the lateral direction stabilize the array.

PMID- 12202395
TI  - Prevention of B cell antigen receptor-induced apoptosis by ligation of CD40
      occurs downstream of cell cycle regulation.
AB  - Cross-linking of the B cell antigen receptor (BCR) on germinal center B cells can
      induce growth arrest and apoptosis, thereby eliminating potentially autoreactive
      B cells. Using the Burkitt lymphoma cell line Ramos as a model, we studied the
      commitment to apoptosis following growth arrest, as well as how triggering of
      CD40 or addition of tumor necrosis factor (TNF)-alpha can interfere to block cell
      death. Both BCR triggering and direct induction of growth arrest by sodium
      butyrate (n-But) caused hypophosphorylation of the retinoblastoma protein (pRb),
      followed by apoptosis. Interestingly, although CD40 ligation or TNF-alpha
      efficiently prevented BCR-induced and n-But-induced apoptosis, these co-stimuli
      did not inhibit, but rather augmented, growth arrest. Analysis of cell cycle
      regulators showed that each apoptotic and T(h) stimulus distinctly affected
      cyclins or cyclin-dependent kinase inhibitors, indicating that growth arrest can
      be uncoupled from apoptosis. BCR ligation and growth arrest activated the
      intrinsic or mitochondrial route of apoptosis. CD40 ligation and TNF-alpha
      prevented release of cytochrome c and activation of caspase-3, which could not be
      explained by effects on the expression of Bcl-2, Bcl-x(L) or Bax. Finally, the
      onset of BCR-induced apoptosis occurred after 10-12 h and addition of CD40 mAb or
      TNF-alpha at that point still prevented further execution of apoptosis. We
      conclude that in mature B cells apoptosis is not an obligatory event following
      growth arrest. Instead, commitment to apoptosis can be rapidly controlled by T
      cells via CD40 ligand and TNF-alpha, downstream of the pRb-regulated restriction
      point of the cell cycle, but prior to mitochondrial cytochrome c release.

PMID- 12202396
TI  - Regulation of Ig class switch recombination by NF-kappaB: retroviral expression
      of RelB in activated B cells inhibits switching to IgG1, but not to IgE.
AB  - Mutant NF-kappaB-deficient B cells from knockout mice lacking RelA, p105/p50 or
      the transactivation domain of c-Rel exhibit distinct and selective cell-intrinsic
      defects in their ability to undergo class switch recombination (CSR) to specific
      Ig isotypes. This isotype-specific requirement for particular NF-kappaB
      transcription factors in B cells activated to undergo CSR is intriguing because
      the NF-kappaB composition in B cells is also highly regulated and can vary
      significantly depending upon how B cells are activated. These studies prompted us
      to test by retroviral transduction of normal B cells whether changes in the NF
      kappaB composition in activated B cells could modulate cytokine-driven CSR. RelB,
      RelA, c-Rel, p50 and p52 were first expressed in lipopolysaccharide-activated
      primary B cells and then induced by cytokine addition to undergo CSR to IgG1,
      IgE, IgG2a, IgG2b or IgA. Surprisingly, only retroviral expression of RelB
      altered CSR, resulting in a 3-fold decrease in CSR to IgG1 induced by IL-4. This
      effect was isotype specific as RelB expression did not affect CSR to IgE within
      the same culture or to other isotypes tested. The transactivation domain of RelB
      was required for inhibition of CSR to IgG1. Expression of p50-RelB or p52-RelB
      dimers joined covalently by a flexible peptide linker also specifically inhibited
      IgG1 CSR. RelB-mediated inhibition of IgG1 CSR was associated with a decrease in
      germline gamma1 transcription, but not with changes in proliferation as assayed
      by CFSE labeling. Thus, RelB complexes can specifically inhibit CSR to IgG1, but
      not IgE, in activated, primary B cells.

PMID- 12202397
TI  - Molecular and structural analysis of the panallergen profilin B cell epitopes
      defined by monoclonal antibodies.
AB  - Interactions of five mouse mAb (10A4, 5F2, 9A7, 9G4 and 3H8) and sunflower
      profilin were characterized using synthetic overlapping peptides. All the
      continuous B cell epitopes analyzed in this work were 6-10 amino acids in length,
      and clustered at the N- and C-terminal alpha-helices and a two-stranded segment
      composed of residues 40-50. Mutational analysis of the epitopes revealed that
      single amino acid changes within these peptides had dramatic effects on IgG
      binding characteristics. A three-dimensional molecular model of sunflower
      profilin was generated by homology modeling based on the crystal structure of
      Arabidopsis thaliana profilin. All but one of the murine B cell epitopes defined
      in this work were located on the surface of the profilin molecule in the alpha
      helices (10A4 and 3H8) or in the turns (5F2 and 9G4). In contrast, 9A7 epitope
      was located in the profilin core and partially buried by the C-terminal. Two mAb
      (5F2 and 10A4) inhibited the binding of anti-profilin human IgE up to 52%. In
      contrast, mAb 3H8 seemed to enhance the binding of anti-profilin IgE of sera from
      allergic patients.

PMID- 12202398
TI  - A CD18-dependent protein kinase C beta-mediated alternative cell death pathway of
      activated monocytes.
AB  - Activated monocytes become resistant to numerous death stimuli including death
      receptors. Given that the uncontrolled activation of monocytes/macrophages and
      their persistence can lead to severe inflammatory conditions, it is critical to
      define the pathways that control their elimination. We previously reported that
      ligation of HLA-DR molecules on peripheral blood-derived monocytes induces their
      death. To investigate the mechanisms of HLA-DR-mediated death in monocytes, we
      used the THP-1 monocytic cell line as a model. We show that while THP-1 are
      equally resistant to HLA-DR- and to Fas-mediated death, treatment of THP-1 with
      IFN-gamma renders them sensitive to HLA-DR- but not to Fas-mediated death. Both
      activation of the Src family protein tyrosine kinase and classical protein kinase
      C (PKC) occur through HLA-DR, but only PKC activation is involved in HLA-DR
      mediated death of these cells. Moreover, HLA-DR-mediated cell death of activated
      monocytes implicates a regulatory loop between the HLA-DR/CD18 complex and the
      downstream activation of PKCbeta. Thus, our study identifies an alternative
      physiological signaling pathway of monocyte death, and further investigation on
      its regulation is likely to provide significant insights into the control of
      monocyte homeostasis and inflammation.

PMID- 12202399
TI  - Role of CD44 in activation-induced cell death: CD44-deficient mice exhibit
      enhanced T cell response to conventional and superantigens.
AB  - T cells upon activation are known to up-regulate CD44 expression. However, the
      precise function of CD44 on activated T cells is not clear. In this report, we
      demonstrate that signaling through CD44 plays an important role in activation
      induced cell death (AICD). CD44 knockout (KO) mice had an elevated in vivo
      primary and in vitro secondary response to challenge with conalbumin, anti-CD3
      mAb and staphylococcal enterotoxin A (SEA), which correlated with reduced AICD
      when compared to CD44 wild-type mice. In addition, CD44 KO mice exhibited
      increased delayed-type hypersensitivity response to dinitrofluorobenzene. In a
      model examining in vitro AICD, splenocytes from CD44 KO mice showed resistance to
      TCR-mediated apoptosis when compared to splenocytes from CD44 wild-type mice. In
      addition, signaling through CD44 led to increased apoptosis in TCR-activated but
      not resting T cells from CD44 wild-type mice without affecting Fas expression.
      Injection of SEA into mice deficient in CD44 and Fas (CD44 KO/lpr) led to an
      increased primary response when compared to mice that expressed CD44 but not Fas
      (CD44 WT/lpr), suggesting that the enhanced response to SEA was dependent on CD44
      but not Fas expression. Administration of anti-CD44 mAb into CD44 wild-type mice
      caused a significant decrease in antigen-specific T cell response. Together,
      these data implicate CD44 as an important regulator of AICD in T cells.
      Furthermore, targeting CD44 in vivo may constitute a novel approach to induce
      apoptosis in activated T cells, and therefore to treat autoimmune diseases,
      allograft rejection and graft versus host disease.

PMID- 12202400
TI  - Differential regulation of maturation and apoptosis of human monocyte-derived
      dendritic cells mediated by MHC class II.
AB  - Antigen-driven interaction of dendritic cells (DC) with CD4(+) T(h) cells results
      in the exchange of bidirectional activating signals. Cross-linking of TCR by MHC
      class II-bound antigen activates T(h) cells, resulting in their up-regulation of
      CD40 ligand. Here we show that MHC class II molecules, in addition to their
      passive role in DC-T(h) cell interaction, can also actively induce DC maturation.
      Cross-linking of MHC class II molecules on human monocyte-derived DC results in
      the up-regulation of the surface expression of CD83, CD80, CD86, CD54, CD1a and
      CD40 molecules, the typical DC maturation-associated markers. It also promotes a
      rapid homotypic aggregation of DC paralleled by the up-regulation of such
      adhesion molecules as VLA-4, tissue transglutaminase, CD54 and CD11c. The impact
      of MHC class II cross-linking upon DC was context dependent. The outcome of MHC
      class II signaling depends on the maturation status of DC. While the cross
      linking of MHC class II on immature DC promoted their maturation, the dominant
      effect upon the DC that were previously matured was the induction of DC
      apoptosis. Our current observations indicate that, in addition to the previously
      reported negative impact of MHC class II-mediated signaling on DC function, it
      also promotes DC maturation, participating in the enhancement of DC stimulatory
      function. Importantly, MHC class II-induced DC maturation and apoptosis are
      mediated by different signaling pathways, sensitive to different sets of
      inhibitors. This opens the possibility of differential regulation of each of
      these events in immunotherapy.

PMID- 12202401
TI  - A mouse strain defective for alphabeta versus gammadelta T cell lineage
      commitment.
AB  - As a result of a transgene insertion and chromosomal deletion, a mutant mouse
      strain has been found that is defective in the lineage commitment step that
      produces a balance of alphabeta and gammadelta T cells. The mice produce a
      reduced population of alphabeta CD4 T cells and almost no alphabeta CD8 T cells.
      Within the CD4 and CD8 populations in the thymus there exist abnormal subsets
      that express the gammadelta TCR. These gammadelta TCR-expressing cells populate
      the peripheral lymphoid organs such that up to 75% of the CD8 T cells in the
      lymph nodes and spleen express a gammadelta TCR. Further analyses indicate that
      the regulation that prevents dual TCR expression has been impaired. The locus of
      insertion and deletion was mapped to chromosome 10 26 cM. We have analyzed the
      entire locus and, in addition, the gene expression changes in early thymocytes
      were analyzed by gene array technology. The analysis of this mutant strain
      indicates that the alphabeta versus gammadelta lineage decision can be profoundly
      disregulated independently of successful gene rearrangements.

PMID- 12202402
TI  - NF-kappaB is required for CD38-mediated induction of C(gamma)1 germline
      transcripts in murine B lymphocytes.
AB  - Ligation of CD38 on murine B cells with agonistic anti-CD38 mAb induces B cell
      proliferation, expression of germline gamma1 transcripts and enhances IL-5
      receptor expression. This leads to Ig class switch recombination from the micro
      to gamma1 heavy chain gene, and high levels of IgM and lgG1 production,
      particularly in response to anti-CD38 and IL-5 co-stimulation. Although some of
      the post-receptor signaling events initiated by CD38 ligation have been
      characterized, signaling pathways involved in CD38-mediated germline gamma1
      transcript expression in B cells are poorly understood. Here we show that CD38
      ligation of murine splenic B cells activates members of the NF-kappaB/Rel family
      of proteins including c-Rel, p65 and p50. The activation patterns and kinetics of
      NF-kappaB-like proteins in CD38-stimulated B cells differ somewhat from those
      seen in CD40-stimulated B cells. Activation of NF-kappaB-like proteins by CD38
      ligation is not observed in splenic B cells from Bruton's tyrosine kinase (Btk)
      deficient (Btk(-/-)) mice, with inhibitors of protein kinase C (PKC) and
      phosphatidylinositol (PI)-3 kinase also suppressing NF-kappaB activation in CD38
      activated B cells. We infer from these results that activation of Btk, PI-3
      kinase and PKC play, at least in part, important roles in the induction of NF
      kappaB in CD38-stimulated murine B cells. Consistent with a role for NF
      kappaB/Rel signaling in CD38-mediated germline gamma1 transcript expression, p50(
      /-) B cells show significant impairment of germline gamma1 transcript expression
      in response to CD38 ligation, whereas the CD40-induced response was not altered.
      In contrast, c-Rel(-/-) B cells show a severe impairment of germline gamma1
      transcript expression in response to CD38 or CD40 ligation. These results
      indicate an essential role for NF-kappaB proteins in the induction of germline
      gamma1 transcripts by CD38-ligated murine B cells giving rise to IL-5-induced
      IgG1 production.

PMID- 12202403
TI  - Variable expression of Toll-like receptor in murine innate and adaptive immune
      cell lines.
AB  - Pattern recognition receptors (PRR) play an important roll in immediate responses
      to different conserved molecules produced by microbes. In this paper we describe
      the cloning of the mouse homolog of Toll-like receptor (TLR) 3, and present an
      analysis of the expression of this gene in innate and adaptive immune cell lines.
      We also performed a broad expression study on these cells of other TLR, including
      TLR family members whose expression pattern is not known, i.e. TLR7. The analysis
      was done in order to understand, and possibly predict, how innate and adaptive
      immune cells respond to microbial pattern antigens. This first large-scale
      analysis of immune cell TLR expression in the mouse reveals that cells of the
      innate immune system express a broader number of TLR than cells of the adaptive
      immune system, supporting preconceptions concerning the hierarchy of immune cells
      involved in direct pathogen recognition. Additionally, the expression of TLR
      transcripts by mast cells, neutrophils and microglial cells observed here
      suggests that pathogen-associated molecular pattern molecules could induce
      activation of these cells through TLR. Finally, the mouse homolog of human TLR3
      identified here may, like its human counterpart, be an exceptional TLR molecule
      due to its lack of a conserved proline residue seen to be involved in existing
      TLR signaling capabilities found in other TLR family members.

PMID- 12202404
TI  - Definition of an Fc receptor-related gene (FcRX) expressed in human and mouse B
      cells.
AB  - The recent identification of five human Fc receptor (FcR) homologs, hFcRH1-5, has
      extended the known FcR family and identified an unanticipated richness of the
      chromosome 1q region in genes encoding potential Ig-binding proteins. In a
      database search for additional relatives of this family we identified expressed
      sequence tag representatives of a new FcR-related molecule (hFcRX) and its mouse
      ortholog (mFcRX). The FcRX cDNAs were cloned from human lymph node and mouse
      spleen cDNA libraries. hFcRX is located centromeric of FcgammaRII and FcgammaRIII
      at 1q23, and its mouse ortholog resides in a syntenic region of chromosome 1. The
      genes encode proteins with 67% interspecies identity that lack both N-linked
      glycosylation sites and transmembrane regions. Two of the four FcRX domains are
      Ig-like, and share characteristics similar to FcgammaRI domains 2 and 3, having
      28% overall extracellular identity with hFcgammaRI and 27% identity with
      mFcgammaRI respectively. FcRX transcripts are found primarily in secondary
      lymphoid tissues, where they are expressed by B lineage cells. FcRX thus may
      function as a secreted or intracellular protein in normal and neoplastic B cells.

PMID- 12202405
TI  - What is polycystic ovary syndrome? Are national views important?
AB  - Polycystic ovary syndrome (PCOS) is a true syndrome, being a heterogeneous
      collection of signs and symptoms that gathered together form a spectrum of a
      disorder with a mild presentation in some, whilst in others there is a severe
      disturbance of reproductive, endocrine and metabolic function. There has been
      much debate about phenotype and, more recently, genotype. There has also been
      scepticism in some quarters, with a feeling that we may be looking at one end of
      a spectrum that is in reality 'normal', or perhaps a consequence of the modern
      disease of obesity. Whilst the polycystic ovary is at the centre of the syndrome,
      it is external effects such as hyperinsulinism, that influence its expression.
      There is no consensus on the definition of PCOS and so studies that compare
      epidemiology and treatments often have very different starting points, and so
      cannot be compared. In this debate we wish to re-explore our current thinking on
      PCOS, with a particular emphasis on the British and European perspective and
      invite others to contribute to the discussion which could form the basis for an
      international consensus.

PMID- 12202406
TI  - Alternative treatments in reproductive medicine. The vexing problem of 'seemingly
      impeccable trials...'.
AB  - The problem of 'seemingly impeccable trials' that produce unbelievable results is
      approached from basic notions of the philosophy of science: facts and theory are
      interdependent, and 'crucial experiments' do not exist. This does not lead to an
      'anything goes' attitude, but obliges us to consider arguments and counter
      arguments in the spirit of the 'crossword' analogy by Susan Haack. The role of
      editors and readers might be different: while editors might be under some
      obligation to publish 'seemingly impeccable trials', readers are not obliged to
      accept the findings.

PMID- 12202407
TI  - Should patients with polycystic ovarian syndrome be treated with metformin?
AB  - The recognition of insulin resistance as a principal factor in the pathogenesis
      of polycystic ovarian syndrome (PCOS) has led to the use of insulin-lowering
      agents, also called 'insulin-sensitizing drugs', for its treatment. The most
      extensively studied insulin-lowering agent in the treatment of PCOS is metformin:
      an oral antihyperglycaemic agent used initially in the treatment of type 2
      diabetes mellitus. Metformin is effective in the treatment of PCOS-related
      anovulation and infertility. Moreover, preliminary evidence indicates that
      metformin may also be effective in decreasing the risk of early spontaneous
      miscarriage in women with PCOS. Metformin also appears to induce cardioprotective
      effects on serum lipids as well as plasminogen activator inhibitor (PAI)-1 and
      may decrease the risk of development of type 2 diabetes. The highly promising
      therapeutic profile of metformin is related to the role of this agent in
      controlling an important aetiologic factor in the pathogenesis of PCOS:
      hyperinsulinaemia.

PMID- 12202408
TI  - Should ICSI be the treatment of choice for all cases of in-vitro conception? No,
      not in light of the scientific data.
AB  - There is an ongoing debate among reproductive endocrinologists and embryologists
      about the indications for ICSI in the management of the infertile couple.
      Analysis of published results indicates that there are no data to suggest that
      ICSI should be performed in all cases of in-vitro conception. If the results of
      the basic semen analysis and sperm function tests demonstrate an impairment of
      sperm fertilizing capacity, couples should be directed to ICSI. In cases of
      previous fertilization failure, ICSI usually results in an improved outcome. This
      suggests the presence of 'occult' male or female gamete defects that can be
      bypassed by ICSI. We stress that efforts should be geared toward the
      identification of the aetiology and pathophysiology of sperm and oocyte
      lesions/dysfunctions responsible for fertilization impairment and their potential
      contributions to defective embryogenesis. A better definition of the indications
      for ICSI is needed, together with the development of directed, simpler, less
      expensive and safer alternatives.

PMID- 12202409
TI  - Do women have a hidden heat period?
AB  - This article aims to throw light on the controversial topic of whether women have
      a 'heat' period within their menstrual cycle. The majority of publications in
      this field report, in addition to a periovulatory peak, no changes at all or even
      rises in male- and female-initiated sexual activity, woman's sexual desire,
      autosexual activity and sexual arousability, and interpersonal sexual activities
      during the mid-follicular and late luteal phases. The lack of a distinct pattern
      of women's sexual behaviour across the menstrual cycle may be explained by the
      interplay between cyclical endocrine fluctuations and many psychological, social,
      cultural and environmental factors, as well as the methodological shortcomings
      associated with menstrual cycle research. However, studies focused on cycling
      changes in women's olfactory and visual perception show that, in comparison with
      women at other phases of the menstrual cycle, women at mid-cycle exhibit
      increased sexual motivation that biases recognition performance towards objects
      with a sexual meaning, evaluate the unattractive sweat substance androstenone as
      more pleasant, and display enhanced preference for the odour and face shape of
      masculinized, physically attractive and symmetric men. On the other hand, men
      find the scent of women at mid-cycle more pleasant and sexually attractive than
      during the luteal phase.

PMID- 12202410
TI  - FISH analysis of chromosome X, Y and 18 abnormalities in testicular sperm from
      azoospermic patients.
AB  - BACKGROUND: Sperm extracted from testicular biopsies of azoospermic men can
      successfully be used for ICSI. The concern exists that testicular sperm from
      azoospermic men suffering from severe testicular failure may have a higher
      frequency of aneuploidy, which may lead to an increased risk for chromosomally
      abnormal offspring. METHODS: Testicular sperm from patients showing spermatogenic
      failure (n = 17) and from patients with normal spermatogenesis (n = 26) were
      analysed by fluorescence in-situ hybridization (FISH). Numerical chromosomal
      abnormalities for chromosomes X, Y and 18 were evaluated by FISH in a total of
      1697 testicular sperm derived from 43 azoospermic patients. RESULTS: No
      difference was observed between the frequency of chromosomal abnormalities in
      testicular sperm from patients with normal spermatogenesis (5.6%) and from
      patients with spermatogenic failure (8.2%). However, the frequency of aneuploidy
      for chromosome 18 was higher in the group of azoospermic patients with
      spermatogenic failure than in the group with normal spermatogenesis (3.2 versus
      1.3%). Within the obstructive group, sex chromosome aneuploidy (4.5%) occurred
      more frequently than chromosome 18 aneuploidy (1.3%; P < 0.001). Among testicular
      sperm derived from patients with spermatogenic failure, sex chromosomal
      aneuploidy (5.8%) was similar to that for chromosome 18 (3.2%). CONCLUSIONS: So
      far, no difference in the total frequency of chromosomal abnormalities has been
      observed between patients with normal spermatogenesis and patients with severe
      testicular failure. However, aneuploidy for chromosome 18 was higher in the group
      with spermatogenic failure.

PMID- 12202411
TI  - Manifestation of Y-chromosomal deletions in the human testis: a morphometrical
      and immunohistochemical evaluation.
AB  - BACKGROUND: Deletions of the AZF (azoospermia factor) subregions on the Y
      chromosome are accompanied by a diverse spectrum of spermatogenic disturbances
      ranging from hypospermatogenesis to total depletion of germ cells causing
      infertility. The AZF region encodes gene products which are candidates for the
      genetic control of spermatogenesis. Although it is known which genes are
      involved, a general principle of cause and effect cannot yet be deciphered and
      the deletion type has non-uniform histological phenotypes. METHODS AND RESULTS:
      We analysed morphological parameters of testicular biopsies from 17 patients
      diagnosed for Y chromosome microdeletions. As control groups we analysed testes
      from patients with idiopathic Sertoli cell-only (SCO) syndrome (n = 11), mixed
      atrophy (n = 10) and complete spermatogenesis (n = 11). A detailed genetic
      analysis on the extension of the observed microdeletions revealed similar
      breakpoints in the distal and proximal region of the AZFc region, indicating a
      common mechanism of homologous recombination for such deletions, as has been
      suggested before. Morphometric parameters such as the diameter of the tubules,
      lumen, thickness of the lamina propria and height of the tubule epithelia were
      investigated. The diameter of the tubules from patients with microdeletions was
      found to be significantly smaller compared with patients with mixed atrophy.
      Considering also the size of the tubules, lumen and epithelia, a Y-chromosomal
      microdeletion represents an intermediate state between an idiopathic SCO and
      normal spermatogenesis. The immunohistochemical analysis of six different Sertoli
      cell markers, cytokeratin 18, vimentin, inhibin alpha subunit, 14-3-3 theta, FSH
      receptor and androgen receptor, revealed no impact of AZF deletion on the
      specific expression pattern of these genes. CONCLUSIONS: Our results suggest
      that, notwithstanding the deletion of a common region in the AZFc region,
      microdeletions of the Y chromosome lead to an intermediate status between
      idiopathic SCO and complete spermatogenesis, resulting in a heterogeneous
      histological profile regardless of the seminiferous activity. The Sertoli cell
      function seems not to be altered.

PMID- 12202412
TI  - Natural transmission of a partial AZFb deletion of the Y chromosome over three
      generations: case report.
AB  - The natural transmission of microdeletions of the Y chromosome is occasionally
      reported in the literature. Here we describe the natural transmission of a
      partial AZFb deletion over three generations. PCR amplification of several
      sequence tagged site markers in the three AZF regions of the Y chromosome was
      carried out in a patient with oligoasthenoteratozoospermia, his father and his
      naturally conceived son. The deletion was confirmed by Southern blotting. The
      propositum, his father and his son showed a probably identical, partial deletion
      of the distal part of the AZFb region, involving sY130 and sY143. The deletion
      was confirmed by Southern blotting using the sY130 probe. Partial AZFb
      microdeletions can be associated with moderate oligozoospermia allowing natural
      conception and therefore natural transmission of this genetic anomaly. Further
      studies are needed to define the pathogenetic significance of microdeletions
      involving sY130 and sY143.

PMID- 12202413
TI  - Soluble adhesion molecules in serum throughout the menstrual cycle.
AB  - BACKGROUND: The female reproductive and immune systems are integrally linked with
      respect to shared cellular and molecular mediators. Cell adhesion molecules
      (CAMs) involved in leukocyte-endothelial interactions, e.g. intercellular
      adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1) and E
      selectin, are regulated by sex steroids when expressed by cultured endothelium,
      while uterine and ovarian CAM expression appears to be cyclically or
      gonadotrophin-regulated. METHODS AND RESULTS: To determine if these effects
      translate into changes in soluble CAMs (sICAM-1, sVCAM-1 and sE-selectin) levels
      in peripheral blood, normally cycling women received regular venous sampling
      throughout a complete menstrual cycle. Soluble ICAM-1 levels were maximal in the
      early and mid-follicular stages, progressively decreased throughout the remainder
      of the cycle and were significantly reduced in the late luteal stage (P < 0.001).
      Levels of sVCAM-1 fluctuated during the follicular phase and mid-cycle, but also
      declined in the late luteal phase (P < 0.01), whereas sE-selectin concentration
      did not vary markedly across the menstrual cycle. Plasma hormone and urinary
      hormone metabolite levels confirmed precise cycle tracking and revealed an
      inverse relationship between sICAM-1 and estradiol (r = -0.38, P < 0.005). A
      negative correlation was also apparent between sVCAM-1 and circulating monocyte
      cell numbers (r = -0.47, P < 0.001). CONCLUSIONS: The normal cyclic variation in
      peripheral sICAM-1 and sVCAM-1 levels reported here may reflect uterine and/or
      ovarian tissue remodelling events, and is of particular importance if soluble CAM
      levels are utilized as biological markers of certain disease states in women of
      reproductive age.

PMID- 12202414
TI  - alphavbeta3 integrin expression and pinopod formation in normal and out-of-phase
      endometria of fertile and infertile women.
AB  - BACKGROUND: There is scanty and contradictory information regarding the
      comparison of traditional histological dating criteria of the endometrium with
      the expression of the new markers of endometrial receptivity such as alphavbeta3
      integrin and pinopods. Also, definite data with respect to the potential
      correlation existing between these different new markers in defining the putative
      window of implantation are lacking. METHODS: The temporal relationship between
      alphavbeta3 integrin expression and pinopod formation in normal and out-of-phase
      endometrial biopsies from normal healthy women (n = 12) and infertile patients (n
      = 36) was investigated. Two endometrial biopsies (postovulatory day +7 to +8 and
      4 days later) were performed during a single menstrual cycle in each subject.
      Estradiol and progesterone serum concentrations were quantified on the same days
      as endometrial sampling. RESULTS: No statistically significant difference
      regarding alphavbeta3 integrin expression, pinopod formation, and hormone
      concentrations was found between fertile controls and infertile patients
      irrespective of endometria being in-phase or out-of-phase. Although a coordinate
      high level of expression of alphavbeta3 integrin and pinopod on postovulatory
      days 7-8 was observed, there was an evident lack of temporal co-expression of
      these markers over the luteal phase in the endometrial samples investigated.
      CONCLUSIONS: There is a clear dissociation in the temporal expression of the most
      cited markers postulated to frame the window of implantation. The functional
      significance (if any) of these new markers remains to be established.

PMID- 12202415
TI  - Luteal phase support in infertility treatment: a meta-analysis of the randomized
      trials.
AB  - BACKGROUND: The addition of GnRH agonist to the treatment regimen in women
      undergoing IVF cycles is thought to create a luteal phase defect. In an attempt
      to correct for this, many practitioners supplement with a variety of steroid
      hormones in the luteal phase. METHODS: To determine whether luteal phase support
      increases reproductive success in modern IVF cycles, a systematic review of the
      literature was performed. Meta-analyses were conducted when multiple homogeneous
      studies addressed a single issue. Only randomized controlled trials were included
      in the data analysis. The efficacy of supplementation, as well as the optimal
      route, formulation, dose, and length of administration were queried. RESULTS:
      Luteal supplementation with either i.m. hCG or i.m. progesterone significantly
      improved fertility outcomes compared with no treatment. When comparing i.m.
      progesterone with i.m. hCG, no fertility differences were found. Intramuscular
      progesterone conferred the most benefit compared with oral or vaginal use.
      Addition of oral estrogen to progesterone also improved implantation rates.
      CONCLUSION: Given the increased risk of ovarian hyperstimulation syndrome
      associated with hCG use, i.m. progesterone is favoured for luteal phase
      supplementation with the addition of estrogen.

PMID- 12202416
TI  - Regulation of 11beta-hydroxysteroid dehydrogenase type 1 gene expression in human
      ovarian surface epithelial cells by interleukin-1.
AB  - BACKGROUND: Local modulation of 11beta-hydroxysteroid dehydrogenase (11betaHSD)
      activity, to promote increased availability of anti-inflammatory glucocorticoids,
      is proposed as a compensatory response to inflammatory stimuli. Human 11betaHSD
      type 1 (11betaHSD1) is principally an 11-oxoreductase that reversibly reduces
      cortisone to cortisol. METHODS: Since ovulation is an acute inflammatory process,
      we examined the influence of pro-inflammatory cytokines on expression of
      11betaHSD1 mRNA and metabolism of cortisone to cortisol by human ovarian surface
      epithelium (HOSE) in vitro. RESULTS: Northern analysis showed an approximately
      1.5 kb-sized 11betaHSD1 mRNA transcript in total RNA that was up-regulated
      approximately 3-fold by interleukin (IL)-1alpha (0.5 ng/ml) at 24 h. By real-time
      RT-PCR, induction of 11betaHSD1 mRNA by IL-1alpha was measurable at 6 h and
      maximal at 12 h. Primary HOSE cell cultures also showed low-level 11-oxoreductase
      activity that was stimulated time- and dose-dependently by IL-1alpha and IL
      1beta. The 11betaHSD1 mRNA and 11-oxoreductase responses to 0.5 ng/ILalpha were
      both suppressed by IL-1 receptor antagonist (25 ng/ml). CONCLUSIONS: Cultured
      HOSE cells express IL-1-responsive 11betaHSD1 and 11-oxoreductase activity mRNA
      in vitro. An 11betaHSD1-catalysed increase in anti-inflammatory glucocorticoid
      activity caused by pro-inflammatory cytokines could contribute to the local
      resolution of inflammation during ovulation.

PMID- 12202417
TI  - Myocardial infarction and third generation oral contraceptives: aggregation of
      recent studies.
AB  - BACKGROUND: Arterial cardiovascular and cerebrovascular adverse events associated
      with oral contraceptives (OC) are a major concern to the clinician. This paper
      aggregates the findings of seven recent oral contraceptive studies on the risk of
      acute myocardial infarction (MI) among users of second (2gen) and third (3gen)
      generation OC. METHODS: Odds ratios (OR) from seven original studies published
      between 1996 and 2001 underwent meta-analysis. They had accrued 6464 subjects
      since 1996. In addition, estimates of 22 studies published from 1965 to 1966 were
      synthesized using medians and ranges as an historical point of reference.
      RESULTS: Four meta-analyses were performed for each of the relevant comparisons.
      The point estimates for 3gen versus 2gen OC ranged from 0.44 (0.24-0.80) to 0.62
      (0.38-0.99). Compared with non-users, the aggregated OR for 3gen OC was 1.13
      (0.66-1.92); for 2gen OC it was 2.18 (1.62-2.94). CONCLUSIONS: This overview of
      seven controlled observational studies confirms that 3gen OC do not convey harm
      in regard to MI compared with non-users of OC. The aggregate data and the
      continuing replication of findings allow interpretation of benefit compared with
      older combined OC.

PMID- 12202418
TI  - The kinetics of serum hCG and progesterone in response to oral and vaginal
      administration of misoprostol during medical termination of early pregnancy.
AB  - BACKGROUND: Misoprostol is widely used in combination with mifepristone for
      medical termination of pregnancy. We studied the endocrine parameters of
      trophoblast function during medical termination of early pregnancy using
      mifepristone in combination with oral or vaginal misoprostol. The effect of
      prolonged misoprostol administration was also examined. METHODS: Thirty-four
      women, requesting termination of pregnancy and with <or=63 days of amenorrhoea,
      received 200 mg of mifepristone on day 0, followed by either oral (n = 13) or
      vaginal (n = 21) administration of 0.8 mg of misoprostol on day 2. In 23 cases
      misoprostol administration was continued orally for an additional 7 days. Serum
      samples, collected up to 14 days following the beginning of the treatment, were
      analysed for hCG, progesterone and mifepristone. RESULTS: hCG and progesterone
      concentrations continued to increase until day 2. Following misoprostol, hCG and
      progesterone levels declined by 70.5 +/- 8.8% and 61.3 +/- 16.3% (mean +/- SD)
      respectively, in 24 h. The percentage decline in hCG correlated inversely (P <
      0.05) with the time taken to abort. The peak level of mifepristone measured on
      day 2 did not correlate with the decline in serum hCG or progesterone. The
      kinetics of hCG, progesterone and mifepristone were similar in the different
      treatment groups. CONCLUSIONS: The route and duration of misoprostol
      administration have no effect on the kinetics of serum hCG or progesterone during
      medical termination of early pregnancy.

PMID- 12202419
TI  - Intrauterine insemination with frozen donor sperm. Pregnancy outcome in relation
      to age and ovarian stimulation regime.
AB  - BACKGROUND: The success of intrauterine insemination with donor semen (IUI-DI) is
      likely to be influenced by a number of variables, including age and ovarian
      stimulation (OS) regime. METHODS AND RESULTS: A retrospective analysis of 1056
      treatment cycles in 261 women (212 single heterosexuals and 49 lesbians) was
      conducted to assess the influence of these two variables on pregnancy outcome
      during IUI-DI. The overall pregnancy rate was 10.6%, being 18.5% for women <35
      years, 11.9% in women 35-40 years and 5.4% in women >40 years (P < 0.05). The
      cumulative pregnancy rate (CPR) after eight cycles was 0.86, 0.51 and 0.32
      respectively (P < 0.05). A total of 445 inseminations were performed following
      spontaneous ovulation, 360 following OS with clomiphene citrate (CC) and 251 with
      hMG, the pregnancy rate per cycle being 13, 7.2 and 11.2% respectively. There was
      no statistically significant difference in the pregnancy rate per cycle, CPR or
      multiple pregnancy rate in the three treatment groups. CONCLUSIONS: These results
      indicate that the use of OS with either CC or hMG in women without ovulatory
      dysfunction does not improve the pregnancy rate during IUI-DI. The only factor
      associated with reduced effectiveness of fertility treatment was age, confirming
      that IUI is a poor treatment option for women >40 years of age.

PMID- 12202420
TI  - Long-term fertility prognosis following selective salpingography and tubal
      catheterization in women with proximal tubal blockage.
AB  - BACKGROUND: The possibility of conception following selective salpingography and
      tubal catheterization is believed to decline sharply a few months after the
      procedure. This observation may be due to the relatively small number of patients
      and short follow-up of previous studies. Furthermore, couples with other causes
      of infertility apart from proximal tubal blockage have usually been excluded.
      METHODS: Survival analysis of conceptions of 218 consecutive infertile women with
      proximal tubal blockage who underwent selective salpingography and tubal
      catheterization was performed. There were no exclusion criteria. Follow-up ranged
      from 16 to 56 months. RESULTS: A total of 47.2% of spontaneous conceptions and
      43.2% of all conceptions, apart from those achieved by IVF or ICSI treatments,
      occurred after the first 12 months following selective salpingography and tubal
      catheterization. The decline in the possibility of pregnancy during the study
      period (conception hazard rate) was only minimal. CONCLUSIONS: In a population of
      infertile women with proximal tubal blockage, a significant proportion of
      conceptions occur after the first 12 months following selective salpingography
      and tubal catheterization. The presence of any additional causes of infertility
      in the couple should not be regarded as an absolute contraindication to the
      procedure.

PMID- 12202421
TI  - Serum inhibin B levels measured early during FSH administration for IVF may be of
      value in predicting the number of oocytes to be retrieved in normal and low
      responders.
AB  - BACKGROUND: In a previous study we have found that in normal ovulatory women,
      serum inhibin B levels on days 4-6 of FSH administration correlated with the
      number of oocytes retrieved. In the current study we examined the significance of
      earlier inhibin B measurements in predicting the oocyte number, in both normal
      and low responders. METHODS: Study A consisted of 19 patients undergoing their
      first IVF cycle (n = 10) or had a normal response ( vertical line 6 oocytes
      retrieved, n = 9), while study B consisted of 15 patients with a previous low
      ovarian response (<or=5 oocytes retrieved). All patients had day 3 FSH levels <10
      IU/l. After pituitary suppression, 300 (study A) or 600 IU (study B) of pure FSH
      was administered daily. Serum FSH, inhibin A, inhibin B and estradiol (E(2)) were
      determined prior to and every 1-2 days throughout FSH treatment. RESULTS: Study
      A: oocyte number between 4 and 14 correlated significantly with serum inhibin B
      levels on all days of FSH treatment, and with inhibin A and E(2) late during
      treatment. No correlation was found between inhibin B and when oocyte number was
      >16. Study B: oocyte number correlated significantly with inhibin B and inhibin A
      on all days of FSH treatment, even on day 2 (r = 0.90, P < 0.001 and r = 0.65, P
      < 0.05 for inhibin B and A respectively). No significant correlation was found
      with E(2) levels. In both studies, all patients with inhibin B >100 pg/ml on
      treatment day 2 had >6 oocytes. CONCLUSIONS: Our data suggest that serum inhibin
      B measured early during FSH stimulation may indicate whether sufficient oocytes
      will be retrieved, in both normal and low responders. Serum inhibin B measured
      during early FSH treatment may be of predictive value in monitoring ovarian
      stimulation treatment for IVF.

PMID- 12202422
TI  - Cyclin A1 and gametogenesis in fertile and infertile patients: a potential new
      molecular diagnostic marker.
AB  - BACKGROUND: The study aim was to evaluate cyclin A1 mRNA expression levels as a
      potential molecular diagnostic parameter in the work-up of testicular tissue from
      fertile versus infertile patients. METHODS: Cyclin A1 expression was quantified
      in 55 cryopreserved testicular tissue specimens by fluorescence real-time RT-PCR.
      A conventional histological work-up was performed concomitantly in all tissue
      specimens with additional semi-thin sectioning in all cases of non-obstructive
      azoospermia (n = 12), maturation arrest (n = 17) and Sertoli cell-only syndrome
      (SCOS; n = 9). RESULTS: The mean (+/- SD) normalized cyclin A1 expression
      (N(CyclinA1)) was 3.82 +/- 2.23 relative gene expression (RGE) in tissue
      specimens with normal spermatogenesis, and 0.625 +/- 0.221 RGE in those with
      maturation arrest at the level of early spermatids. Only minimal N(CyclinA1) was
      detected in tissue specimens with spermatogonia only or maturation arrest at the
      level of primary spermatocytes (0.005 +/- 0.008). Cyclin A1 expression was absent
      in the majority of SCOS specimens (0.002 +/- 0.002). CONCLUSIONS: These
      investigations suggested that cyclin A1 expression is altered in cases of
      spermatogenic disorders. Moreover, the level of cyclin A1 mRNA expression
      correlates with gametogenic disorders and seems well suited for a molecular
      diagnostic classification supplementing the histopathological evaluation of
      spermatogenic disorders.

PMID- 12202423
TI  - A pathology of the sperm centriole responsible for defective sperm aster
      formation, syngamy and cleavage.
AB  - BACKGROUND: In the present report we analyse the structural and functional
      features of sperm from a patient with severe asthenoteratozoospermia and failure
      of cleavage after ICSI. METHODS: Sperm were studied by phase contrast and
      transmission electron microscopy and microinjected into bovine oocytes to examine
      aster formation using antibodies against acetylated alpha- and beta-tubulins.
      RESULTS: Acephalic sperm, headless tails and abnormal alignments of the head-tail
      junction were observed. Flagella evidenced the features of dysplasia of the
      fibrous sheath. Bovine oocytes injected with patient's sperm showed male and
      female pronuclei but a faulty development of microtubules from the sperm-derived
      centrosome. The first ICSI attempt using conventional sperm selection methods
      resulted in fertilized two pronuclei zygotes, but no syngamy or cleavage. Three
      more ICSI attempts were performed, carefully avoiding sperm with obvious
      anomalies of the connecting piece. Fertilization and cleavage took place in all
      cycles, and in two of them positive betahCG plasma levels were detected but
      preclinical abortions ensued. CONCLUSIONS: We propose that the alterations in the
      head-tail junction and attachment, responsible for the observed sperm phenotype,
      result from centriolar dysfunctions that cause insufficient sperm aster
      formation, lack of syngamy and cleavage or defective embryos leading to early
      abortions.

PMID- 12202424
TI  - Fertilization and embryo development in a mouse ICSI model using human and mouse
      sperm after immobilization in polyvinylpyrrolidone.
AB  - BACKGROUND: For human ICSI, sperm are normally immobilized immediately prior to
      injection. However, there are some situations when only sperm of questionable
      viability are available. There are few evaluations of fertilization or
      developmental problems in human or animal models using sperm having known
      intervals between immobilization and injection. METHODS: Immobilized human sperm
      were maintained for 1-24 h in 10% polyvinylpyrrolidone (PVP) before injection
      into mouse oocytes. Mouse sperm heads were similarly maintained in either PVP or
      a high potassium-containing 'nucleus isolation medium' (NIM) before ICSI and
      embryo development to the blastocyst stage. RESULTS: Immobilized human sperm
      activated mouse oocytes comparably to controls even 24 h after immobilization.
      However, mouse sperm heads showed a decrease in activating ability 6 h after
      isolation, either in PVP or NIM. A significant reduction in blastocyst
      development occurred if mouse sperm heads were maintained for even 1 h in PVP.
      After 6 h, no blastocysts formed, with arrest occurring at the morula stage. NIM
      provided partial protection for up to 3 h. CONCLUSIONS: Immobilized human sperm
      maintained oocyte activating activity for 24 h. However, mouse sperm are
      susceptible to alterations that affect both fertilization and development.

PMID- 12202425
TI  - Outcome of first and repeated testicular sperm extraction and ICSI in patients
      with non-obstructive azoospermia.
AB  - BACKGROUND: It is unclear whether or not testicular sperm extraction (TESE)
      should be repeated for patients in whom no sperm were found during their first
      TESE attempt. METHODS AND RESULTS: The outcome of repeated TESE was evaluated in
      patients with non-obstructive azoospermia (NOA) after failing to obtain sperm in
      their first extraction attempt, or having used all available cryopreserved
      testicular tissue. Out of 83 patients with NOA, patients repeated TESE two (n =
      22), three (n = 8), four (n = 6) and five (n = 3) times. Distribution of main
      testicular histology included germ cell aplasia (55%), maturation arrest (29%)
      and germ cell hypoplasia (16%). The first TESE yielded mature sperm for ICSI in
      39% of patients (sp+), and failed in the remaining 61% (sp-). A second TESE
      yielded mature sperm in 1/4 from the sp- group and in 16/18 from the sp+ group.
      At the third, fourth and fifth trials, 8/8, 5/6 and 3/3 of the original sp+
      patients were sp+ again respectively. Compared with the outcome of the first
      trial, all further trials did not differ statistically in the rate of
      fertilization (54 versus 49%), implantation (9.5 versus 5.4%), or clinical
      pregnancy/cycle (19 versus 15%). No pregnancies were achieved among the three
      patients after their fifth TESE. Pregnancies occurred in all histological groups,
      except maturation arrest. CONCLUSIONS: The outcome of repeated TESE cycles, up to
      the fourth trial, justifies the procedure.

PMID- 12202426
TI  - Fertilization in vitro increases non-disjunction during early cleavage divisions
      in a mouse model system.
AB  - BACKGROUND: We have been studying an unusual mouse-the BALB/cWt (Wt) male-in
      which the Y chromosome is susceptible to high rates of mitotic non-disjunction,
      particularly at the first two cleavage divisions. As these are the same divisions
      that human embryos generated through assisted reproductive technology must
      complete in an artificial setting, analysis of the Wt Y chromosome allows us to
      examine the effect of fertilization and culture in vitro on mammalian chromosome
      segregation. METHODS: We performed standard mouse IVF, cultured embryos in 5% CO2
      in air or in a lowered oxygen atmosphere, and used fluorescence in-situ
      hybridization to examine the sex chromosome constitutions of 2-, 4-, 8- and 16
      cell stage Wt Y-bearing embryos. RESULTS: We observed a significant increase in
      mosaic sex chromosome aneuploidy at each embryonic stage in embryos cultured in
      5% CO2 in air, but under lowered oxygen conditions mosaicism returned to control
      (in-vivo) levels. CONCLUSIONS: Our results demonstrate that slight alterations in
      in-vitro conditions may have a considerable impact on the genetic quality of
      assisted reproductive technology-derived embryos and suggest that the genetic
      quality of embryos should be a fundamental concern in the development of new
      culture systems for clinical use.

PMID- 12202427
TI  - The plane of first cleavage is not related to the distribution of sperm
      components in the mouse.
AB  - BACKGROUND: Marking experiments using phytohaemagglutinin (PHA) and Concanavalin
      A (ConA) have suggested that the first cleavage plane is related to the point of
      sperm entry. Because of concerns about the specificity of lectin binding, the
      distribution of sperm components has been investigated directly. METHODS AND
      RESULTS: The sperm tail could be identified in cleaving zygotes and early 2-cell
      stages following their permeabilization and exposure to Oregon Green Paclitaxel.
      At neither stage did the anterior end of the tail, which lies initially at the
      site of sperm entry, bear a consistent relationship to the first cleavage plane,
      even when it had clearly retained its original location. Moreover, using
      artificial insemination with MitoTracker-labelled sperm, the midpiece was found
      to remain associated with anterior end of the tail through to the 2-cell stage.
      Lectins showed no discernible binding to the fertilization cone of mechanically
      denuded zygotes and very strong binding to the zona pellucida. Moreover, after
      general labelling of zygotes with either ConA or PHA, persisting surface lectin
      tended to be concentrated towards the cleavage plane. CONCLUSION: The present
      findings challenge the claim that the sperm specifies the plane of first
      cleavage, and also question the methodology on which it was based.

PMID- 12202428
TI  - Adenovirus gene transfer vector toxicity to mouse embryos: implications for human
      IVF.
AB  - BACKGROUND: The promulgation and diversification of micromanipulation procedures
      which open the zona pellucida of the oocyte or early embryo is steadily
      increasing the chance that zygotes will encounter infectious viral agents or gene
      transfer vectors derived from these agents. Such interactions could lead to toxic
      effects on the embryo or to insertion of foreign genes into the germ line.
      Adenovirus is a ubiquitous human viral pathogen that is commonly used as a gene
      therapy vector. However, the toxicity of this virus or its vector derivatives to
      embryos has not been extensively investigated. METHODS: In the present study, a
      mouse model was used to investigate the time of appearance of embryo toxicity,
      the manifestations of that toxicity, and the mechanism by which adenoviruses
      exert toxicity. The effects of exposure to adenovirus on in-vivo embryo
      development was also examined. RESULTS: These vectors exerted no deleterious
      effects until after the 2-cell stage, where they caused developmental delay and
      disorganized cleavage. Toxicity was associated with expression of a lacZ reporter
      gene cloned into the vectors, and with the proportion of infectious particles
      within the virus preparations: preparations with a high proportion of 'empty
      capsids', including a preparation of wild-type virus, were less toxic than a
      replication-defective vector with a high proportion of functional, infectious
      particles. Subzonal insertion of adenovirus vector followed by embryo transfer
      led to a dramatic reduction in the number of embryos which developed to term
      findings which establish the physiological significance of the findings from in
      vitro culture. CONCLUSIONS: These results indicate that adenoviruses and their
      vector derivatives are not likely to insert genetic material into the germ line,
      but they may pose a significant threat to the viability of human embryos
      undergoing opening of the zona pellucida during IVF.

PMID- 12202429
TI  - Cytogenetic analysis of giant oocytes and zygotes to assess their relevance for
      the development of digynic triploidy.
AB  - BACKGROUND: In order to assess the role of binucleate giant oocytes for
      generating digynic triploidy, we studied their frequency, maturation patterns and
      chromosomal complements at metaphase II (MII) or after fertilization. METHODS:
      Uncleaved, giant zygotes were incubated with podophyllotoxin and vinblastine,
      treated with hypotonic solution and fixed by a gradual fixation method. Giant MII
      oocytes were directly subjected to hypotonic treatment. The chromosomes were
      stained with Giemsa. RESULTS: A total of 7065 oocytes were collected during the
      study period, of which 18 (0.26%) were classified as giant cells. When
      considering only those patients in whom giant cells were identified (among other
      normal sized cells) a giant cell frequency of 18/237 (7.6%) was found. Nine cells
      underwent a union of the nuclei during maturation to MII and four of them became
      fertilized showing two pronuclei. Seven oocytes maintained the binucleate state
      to MII and one of them was fertilized showing three pronuclei. Ten unfertilized
      cells were available for cytogenetic analysis and proved to be diploid. All five
      giant zygotes revealed triploidy. CONCLUSIONS: The data suggest that giant
      oocytes may play an important, yet underestimated role in causing digynic
      triploidy. We recommend the exclusion of giant oocytes from IVF trials and that
      giant cells should be discarded, even if they carry the regular number of two
      pronuclei.

PMID- 12202430
TI  - Morphological and cytogenetic analysis of human giant oocytes and giant embryos.
AB  - BACKGROUND: Giant binuclear oocytes occur with considerable frequency in human
      ovaries, but their ultimate fate remains unknown. We report the morphology,
      cytogenetics and developmental potential of human giant oocytes from patients
      undergoing assisted reproductive technologies. METHODS AND RESULTS: A total of 44
      giant oocytes was collected from patients aged 22-44 years old, with an overall
      frequency of 0.3% (44/14 272 oocytes). Giant oocytes were approximately 30%
      larger in diameter than normal oocytes (mean 200.4 versus 154.7 micro m, P =
      0.0001). Two different morphological patterns were observed among giant
      unfertilized and fertilized oocytes. All unfertilized oocytes appeared to be
      diploid and contained either one or two metaphase plates (46 or 2 x 23
      chromosomes), and one or two polar bodies respectively. Consequently, fertilized
      giant oocytes exhibited either two or three pronuclei, or two or four polar
      bodies. Both types of giant zygotes were capable of normal cleavage and
      development to blastocyst stage. Four giant embryos were analysed by interphase
      fluorescence in-situ hybridization using probes for chromosomes 9, 22, X and Y,
      and all appeared chromosomally abnormal with numerical alterations indicative of
      ploidy change. CONCLUSIONS: Giant oocytes might be a possible source of human
      digynic triploidy. To avoid undesired miscarriages, giant embryos originated from
      either two- or three-pronuclear giant zygotes should be excluded from uterine
      transfers.

PMID- 12202431
TI  - High outcome predictability after IVF using a combined score for zygote and
      embryo morphology and growth rate.
AB  - BACKGROUND: A scoring system has been developed to determine preimplantation
      embryo quality, and used to select embryos for transfer into the uterus of
      patients. METHODS AND RESULTS: The system was used to study early embryo
      development and to test whether these scores alone can accurately predict IVF
      outcome. Following zygote and embryo scores through early development, the data
      showed that a top quality zygote does not necessarily indicate that the resulting
      embryo will be top quality after in-vitro culture. The embryo quality score can
      change dramatically when embryos are cultured to day 2 or 3 post-fertilization.
      Pregnancy rates and implantation rates were compared with the cumulative and
      separated zygote and embryo scores. Analysis of the predictability of scoring
      systems suggested that morphological scores alone are relatively unpredictive of
      IVF outcome. When weighted for in-vitro growth rate, scores were highly
      predictive, more so than the rate of development alone. CONCLUSIONS: These data
      suggested that a combination of in-vitro growth rate and morphological analysis
      both of zygotes and embryos was highly indicative of outcome after IVF. The
      results can be adopted to the single embryo transfer approach to IVF.

PMID- 12202432
TI  - Higher cortisol:cortisone ratios in the preovulatory follicle of completely
      unstimulated IVF cycles indicate oocytes with increased pregnancy potential.
AB  - BACKGROUND: Conception following gonadotrophin-stimulated IVF and embryo transfer
      has been associated with a higher intrafollicular cortisol:cortisone ratio and
      decreased metabolism of cortisol to cortisone. The role of glucocorticoids in
      human oocyte maturation is not fully understood, but active glucocorticoid
      (cortisol) may be important. This study relates intrafollicular cortisol and
      cortisone concentrations to oocyte fertilization and embryo implantation in
      unstimulated cycles. METHODS: Patients aged <40 years with favourable sperm
      underwent unstimulated IVF-embryo transfer. Study 1 related intrafollicular
      cortisol levels to oocyte and IVF outcome: (i) fertilized, pregnant (n = 9); (ii)
      fertilized, not pregnant (n = 21); and (iii) unfertilized (n = 12). Study 2 was a
      case-control study of 27 patients (same outcome groups of equal size) which
      measured intrafollicular cortisol, cortisone and the cortisol:cortisone ratio.
      RESULTS: Conception cycles demonstrated higher cortisol concentrations compared
      with the fertilized group (study 1) [median (95% confidence interval): 299 (249
      330) versus 227 nmol/l (185-261); P < 0.05] and higher cortisol:cortisone ratios
      when compared with the unfertilized group (study 2) [7.38 (5.23-9.19) versus 3.56
      (1.75-7.46) respectively; P = 0.02]. Of the women with cortisol:cortisone ratios
      greater than the outcome independent mean of 5.90, 58% conceived compared with
      only 13% with ratios <5.90 (P < 0.02). CONCLUSION: Higher cortisol:cortisone
      ratios in conception cycles suggest that active glucocorticoid may be important
      for final oocyte maturation and embryo implantation in unstimulated cycles.

PMID- 12202433
TI  - First polar body morphology and blastocyst formation rate in ICSI patients.
AB  - BACKGROUND: It may be beneficial to identify, at a very early stage of
      development, concepti that will result in viable blastocysts by using a non
      invasive technique. METHODS: Homogeneous groups in terms of first polar body (PB)
      morphology were analysed with regard to fertilization, embryo quality and
      blastocyst formation. The strategy was to transfer a maximum of two blastocysts
      with an adequate inner cell mass deriving from oocytes with identical first PBs
      in order to obtain information about the actual implantation potential. RESULTS:
      A significant relationship between first PB morphology and embryo quality was
      found. Fragmentation after 2 days was increased in embryos derived from oocytes
      with fragmented first PBs (P < 0.05) in comparison with those derived from
      oocytes with intact PBs. No similar correlation could be demonstrated for
      fertilization rate. Embryos in the intact first PB group showed an increased rate
      of blastocyst formation as compared with the fragmented first PB group (P <
      0.05). In addition, a significant difference in implantation rate (48.6 versus
      22.0%; P < 0.025) and ongoing pregnancy rate (68.4 versus 34.8%; P < 0.05) was
      observed for the intact versus fragmented groups respectively. CONCLUSION: In
      conclusion, the current study provides further evidence that preselection at a
      very early stage may be helpful in identifying a subgroup of preimplantation
      embryos with a good prognosis to form blastocysts and, consequently, to implant.

PMID- 12202434
TI  - An improved protocol for dilution of cryoprotectants from vitrified human
      blastocysts.
AB  - BACKGROUND: The purposes of this study were to compare the survival rate of human
      blastocysts thawed by two different methods after vitrification using electron
      microscopic (EM) grids, and to report the successful pregnancies and live births
      resulting from the transfer of blastocysts that had survived the established
      thawing method. METHODS: The blastocysts produced from three pronuclei zygotes in
      IVF cycles were vitrified on an EM grid. After dilution of cryoprotectant by
      either a 6- or 2-step method, the survival rate of the blastocysts was compared.
      RESULTS: The survival rate of blastocysts thawed using the 6-step method (82.6%,
      100/121) was significantly higher than that of the 2-step method (50.6%, 87/172;
      P < 0.01). Therefore, we applied the 6-step method in our blastocyst
      cryopreservation programme. Overall, 34.1% (14/41) of clinical pregnancies and 11
      live births were achieved. CONCLUSIONS: The present results indicated that a 6
      step thawing method was more effective than a 2-step thawing method for thawing
      vitrified human blastocysts.

PMID- 12202435
TI  - Rescue ICSI of unfertilized oocytes after IVF.
AB  - BACKGROUND: Failed fertilization after IVF occurs in 10-20% of cycles.
      Conflicting results of rescue fertilization by ICSI have been reported. We
      therefore compared the success rate in terms of fertilization and pregnancy of
      cycles in which rescue ICSI was performed with those from a matched control group
      of primarily ICSI cycles. METHODS: Unfertilized oocytes from IVF cycles with
      total fertilization failure where at least four metaphase II oocytes were
      available were treated by ICSI (group I; n = 120). A matched control group was
      established with patients undergoing ICSI during the same period (group II; n =
      280). RESULTS: Both fertilization rate and the proportion of embryos with four
      blastomeres on day 2 after ICSI were significantly higher in the control group (P
      < 0.05). Embryo quality, however, was comparable in both groups. The pregnancy
      rate in the control group was 25.3% whereas in group I with rescue ICSI, no
      pregnancy was obtained. CONCLUSIONS: Although unfertilized oocytes after IVF can
      be fertilized by ICSI, the developmental potential of the ensuing embryos is very
      poor. Therefore, rescue ICSI after total failure of fertilization is not
      recommended.

PMID- 12202437
TI  - Advanced operative office hysteroscopy without anaesthesia: analysis of 501 cases
      treated with a 5 Fr. bipolar electrode.
AB  - BACKGROUND: The aim of this study was to evaluate treatment efficacy and patient
      acceptability of a new bipolar probe used during office hysteroscopic treatment
      of benign intrauterine pathologies. METHODS: In this observational clinical
      study, 501 women were treated for benign intrauterine pathologies using an office
      hysteroscopic procedure, without analgesia or anaesthesia. A Versapoint 5 Fr.
      bipolar electrical generator was used to treat endometrial polyps ranging between
      0.5 and 4.5 cm, as well as submucosal and partially intramural myomas between 0.6
      and 2.0 cm. Treatment efficacy and patient compliance were evaluated. RESULTS: At
      follow-up, the uterine cavity was normal in all patients without any recurrence
      or persistence of the pathology. One focal adenocarcinoma was discovered at
      histology in an endometrial polyp of a menopausal patient. Patient acceptance was
      satisfactory; 47.6-79.3% of the patients underwent the procedure without
      discomfort. CONCLUSIONS: The combination of a new generation small diameter
      hysteroscope and a new bipolar 5 Fr. electrode enables the gynaecologist to treat
      intrauterine pathologies in an office setting without anaesthesia.
      Experimentation of a special set-up of the electrical generator reduced patient
      discomfort during the operative part of the hysteroscopic procedure.

PMID- 12202436
TI  - Surface vascularization and endometrial appearance in women with menorrhagia or
      using levonorgestrel contraceptive implants. Implications for the mechanisms of
      breakthrough bleeding.
AB  - BACKGROUND: Women using progestogen-only contraceptives are commonly troubled by
      irregular bleeding. Endometrial vessel breakdown and repair is thought to be
      locally regulated under the indirect influence of sex steroids. Most information
      about endometrial vessels is derived from blind biopsies taken in an outpatient
      setting. Hysteroscopy allows in-vivo observation of the whole endometrial
      surface, including vessel morphology, distribution and areas of bleeding, as well
      as information about non-vascular structures that may not be accessible from
      biopsies. METHODS: Hysteroscopies were performed on 34 women using the
      levonorgestrel contraceptive implant system (Norplant(TM)) and in a comparison
      group of 20 women complaining of menorrhagia due to ovulatory dysfunctional
      bleeding. The images were captured and vascular appearances assessed using image
      analysis. RESULTS: The percentage of the superficial endometrium covered with
      blood vessels was found to be significantly greater in Norplant users compared
      with the comparison group (P = 0.0006). More superficial vessels were seen in
      those with recent frequent or prolonged bleeding and spotting (P < 0.0001). In
      Norplant users, but not in the comparison group, superficial vascular
      distribution was predominantly patchy (P < 0.0001). Unusual vascular appearances
      classified as 'neovascular' (P < 0.0001) and 'mosaic' (P < 0.0001) patterns were
      commonly seen in Norplant users but not in the comparison group. The
      hysteroscopic appearance of the endometrial epithelium, glands and stroma also
      differed between Norplant users and women with menorrhagia. Apparent shedding of
      the superficial endometrium was commonly seen by hysteroscopy in Norplant users
      during a bleeding episode (P < 0.0001). Prominent gland openings with thick mucus
      were commonly seen in Norplant users and small sessile polyps were seen in six
      cases. CONCLUSIONS: These hysteroscopic observations provide further evidence
      that exposure to progestogens alters the superficial endometrial vasculature and
      may interfere with angiogenesis.

PMID- 12202438
TI  - Aberrant cytokine production by peripheral blood mononuclear cells in recurrent
      pregnancy loss?
AB  - BACKGROUND: Successful pregnancy may depend on a Th2-type cytokine response,
      whilst, conversely, a poor pregnancy outcome may be associated with an increase
      in Th1 cytokines and a concomitant decrease in Th2 cytokines. This prospective
      study was designed to elucidate whether a failure of the cytokine shift pre-dated
      miscarriage and was therefore likely to be an aetiological factor in recurrent
      pregnancy loss (RPL). METHODS: Cytokine production by stimulated peripheral blood
      mononuclear cells from 46 pregnant women who had previously suffered idiopathic
      RPL during early pregnancy was compared with 25 gestationally age-matched
      pregnant controls and 11 non-pregnant women. RESULTS: Production of IFN-gamma was
      lower in pregnant than in non-pregnant women and even lower in RPL pregnant women
      (P = 0.0191). IL-10 was increased in pregnant women compared with non-pregnant
      controls, and further increased in RPL patients (P = 0.026). IL-4 was also
      increased in women with RPL (P = 0.0001). No differences in IFN-gamma, IL-10 or
      IL-4 secretion were observed in RPL patients who subsequently miscarried compared
      with those who successfully completed the pregnancy. RPL women with a successful
      reproductive outcome had similar concentrations of TNF-alpha to pregnant women,
      RPL women who subsequently miscarried had significantly lower levels than either
      pregnant women (P = 0.02) or non-pregnant controls (P = 0.0004). CONCLUSIONS:
      Contrary to our hypothesis, the cytokine shift, which appears to characterize
      normal pregnancy, was accentuated rather than diminished in RPL pregnant women.

PMID- 12202439
TI  - Management of miscarriage: a randomized controlled trial of expectant management
      versus surgical evacuation.
AB  - BACKGROUND: In many countries, surgical uterine evacuation is the standard
      treatment for women with a miscarriage, but expectant management has been
      advocated as an alternative. The choice between the two options cannot be based
      on published evidence alone, because randomized clinical trials are scarce while
      generalizability of findings to patients with a strong preference for either
      management options is unclear. METHODS: In a randomized controlled trial, the
      complications and efficacy of either expectant or surgical management for
      miscarriages were compared, and the results in patients who refused randomization
      and were managed according to their own preference were studied. In total, 122
      patients were randomized and 305 were managed according to their choice. RESULTS:
      No differences were found in the number of emergency curettages and complications
      between expectant and surgical management. Efficacy at 6 weeks was 30/64 (47%) in
      women allocated to expectant management, and 55/58 (95%) in women allocated to
      surgical evacuation. After 7 days, 37% of expectantly managed women had a
      spontaneous complete miscarriage. After 6 weeks, intention-to-treat analysis
      including cross-overs showed similar effectiveness (92% versus 100%). Results in
      the preference groups were comparable with those in the randomized groups.
      CONCLUSION: In our experience a waiting period of 7 days after diagnosis may
      prevent 37% of surgical procedures.

PMID- 12202440
TI  - D-chiro-inositol is more effective than myo-inositol in preventing folate
      resistant mouse neural tube defects.
AB  - BACKGROUND: Among mouse genetic mutants that develop neural tube defects (NTDs),
      some respond to folic acid administration during early pregnancy, whereas NTDs in
      other mutants are not prevented. This parallels human NTDs, in which up to 30% of
      cases may be resistant to folic acid. Most spina bifida cases in the folic acid
      resistant 'curly tail' mouse can be prevented by treatment with inositol early in
      embryonic development. Here, the effectiveness and safety during pregnancy of two
      isomers, myo- and D-chiro-inositol, in preventing mouse NTDs was compared.
      METHODS AND RESULTS: Inositol was administered either directly to embryos in
      vitro, or to pregnant females by s.c. or oral routes. Although D-chiro- and myo
      inositol both reduced the frequency of spina bifida in curly tail mice by all
      routes of administration, D-chiro-inositol consistently exhibited the more potent
      effect, reducing spina bifida by 73-86% in utero compared with a 53-56% reduction
      with myo-inositol. Pathological analysis revealed no association of either myo-
      or D-chiro-inositol with reduced litter size or fetal malformation. CONCLUSIONS:
      D-chiro-inositol offers a safe and effective method for preventing folic acid
      resistant NTDs in the curly tail mouse. This raises the possibility of using
      inositol as an adjunct therapy to folic acid for prevention of NTDs in humans.

PMID- 12202441
TI  - Complete hydatidiform mole and normal live birth: a novel case of confined
      placental mosaicism: case report.
AB  - Hydatidiform molar change, characterized by abnormal fetoplacental development
      and placental villous trophoblast hyperplasia, results from genetically abnormal
      conception, in which there is an excess of paternally derived genetic material.
      The majority of pregnancies in which molar change has been reported in
      association with a live fetus represent dizygotic twin pregnancies in which one
      fertilization results in a complete hydatidiform mole (CM) and the other a normal
      co-twin. In such cases, there is usually a clear distinction, both
      sonographically and pathologically, between the molar and non-molar regions of
      the placenta. We present a singleton pregnancy, with diffuse placental molar
      change detected prenatally, which resulted in a chromosomally and phenotypically
      normal female infant at term. Pathological examination revealed the presence of
      intermixed populations of morphologically normal chorionic villi and villi with
      the characteristics of CM. Studies of genetic polymorphisms demonstrated that the
      CM, normal villi and fetus were all derived from the same sperm; the fetus was
      diploid and biparental whereas the areas of pathological CM were androgenetic and
      monospermic. We believe this represents the first well-documented case of
      apparent confined placental mosaicism involving CM and a coexisting normal fetus,
      which has presumably arisen following mitotic abnormalities in the early post
      fertilization period.

PMID- 12202442
TI  - Preimplantation genetic diagnosis: patients' experiences and attitudes.
AB  - BACKGROUND: This study aims to report the experiences and attitudes of patients
      who have undergone preimplantation genetic diagnosis (PGD). The extent to which
      this technique is acceptable to the individuals for whom it is intended is
      relatively unexplored, and remains a crucial issue that may ultimately determine
      the value of PGD as an alternative to prenatal diagnosis in high-risk couples.
      METHODS: An information sheet and questionnaire was distributed to 67 couples who
      had been treated at the Hammersmith Hospital, London and the Dexeus Institute,
      Barcelona. RESULTS: One-third of patients had an affected child, over half had
      previous experience of conventional prenatal diagnosis and over one-third had had
      terminations of pregnancy because of a genetic risk. Patients perceive the main
      advantage of PGD to be that only unaffected embryos are transferred to the uterus
      and thus therapeutic termination of pregnancy can be avoided; the main
      disadvantage is the low success rate. A total of 41% of patients found the
      treatment cycle extremely stressful, and, of the 20 patients who had experienced
      both prenatal diagnosis and PGD, 40% of patients found PGD less stressful,
      although 35% experienced more stress. Of those couples who contemplated a further
      pregnancy 76% would choose PGD, 16% would opt for prenatal diagnosis, and 8% no
      tests at all. CONCLUSIONS: The experience of prenatal diagnosis and termination
      of pregnancy can be an unwelcome memory and this leads to a demand for an
      alternative approach. Our data suggest that PGD is acceptable to patients and is
      a valuable alternative to prenatal diagnosis.

PMID- 12202443
TI  - Higher sperm counts in Southern Sweden compared with Denmark.
AB  - BACKGROUND: A common aetiology behind time-related deterioration of male
      reproductive function, including decline of sperm concentration and rising
      incidence of testicular cancer and cryptorchidism, has been suggested.
      Accordingly, a high incidence of testicular cancer and low sperm counts have been
      observed in Denmark, while in Finland opposite figures were found. This may be
      due to genetic factors. The incidence of testicular cancer is 50% lower in Sweden
      than in Denmark. Data on sperm counts in a population of Danish military
      conscripts have been published and we wished therefore to compare them with semen
      parameters in a corresponding cohort from Southern Sweden, geographically and
      genetically very closely related to Denmark. METHODS: A total of 305 military
      conscripts was recruited and investigated in an identical way as those in the
      Danish study including a questionnaire, physical examination and semen analysis.
      RESULTS: Men born and raised in Sweden had a 23% higher mean sperm concentration,
      a 31% higher mean total sperm count and a 14% higher seminal volume compared with
      their Danish counterparts. CONCLUSIONS: The differences in reproductive
      parameters between the two genetically very similar populations could not be
      explained by possible confounders and may be due to unknown environmental or
      lifestyle-related factors.

PMID- 12202444
TI  - Does early growth influence timing of the menopause? Evidence from a British
      birth cohort.
AB  - BACKGROUND: Few adult environmental or behavioural factors have been consistently
      associated with age at menopause. The peak number of follicles attained in utero
      or lost before ovulation begins may be more important. This study investigates
      whether birthweight, childhood body size, having been breastfed and early
      socioeconomic circumstances are associated with age at menopause. METHODS:
      Menopausal status and risk factor information have been collected prospectively
      from 1572 British women followed up since their birth in 1946, so far until 53
      years. Cox's regression models were used to investigate the relationships between
      early life factors and rate of menopause. RESULTS: Age at menopause varied by
      duration of breastfeeding, weight at age 2 years, childhood socioeconomic status,
      but not birthweight. In a multiple regression model, women of low weight at 2
      years had an earlier menopause [hazard ratio (HR) = 0.75 for highest versus
      lowest quarter: 95% confidence interval (CI) 0.54-1.02] and those who had been
      breastfed had a later menopause (HR = 0.69 for vertical line 7 months versus
      never breastfed: 95% CI 0.51-0.92) than others. The influence of socioeconomic
      status was attenuated. CONCLUSIONS: Early life influences may influence ovarian
      ageing, highlighting the importance of investigating factors from across the life
      course.

PMID- 12202445
TI  - Metformin and FSH for induction of ovulation in women with polycystic ovarian
      syndrome.

PMID- 12202447
TI  - Factor V Leiden and recurrent miscarriage.

PMID- 12202449
TI  - Quantification of Doppler signal in polycystic ovarian syndrome using 3D power
      Doppler ultrasonography.

PMID- 12202450
TI  - IVF outcome and intramural fibroids not compressing the uterine cavity.

PMID- 12202452
TI  - Weygandt's On the Mixed States of Manic-Depressive Insanity: a translation and
      commentary on its significance in the evolution of the concept of bipolar
      disorder.
AB  - Wilhelm Weygandt's Uber die Mischzustande des manisch-depressiven Irreseins (On
      the Mixed States of Manic-Depressive Insanity) describes and conceptualizes mixed
      states of mood, behavior, and thinking commonly found in manic-depressive
      disorders. These ideas emerged from Weygandt's service in the 1890s at the
      Psychiatric Clinic of the University of Heidelberg, directed by Emil Kraepelin.
      In the sixth (1899) edition of Kraepelin's influential textbook, the concept of
      manic-depressive illnesses underwent a fundamental shift from a complex group of
      syndromal subtypes to a single integrated disorder, widely known from the 1921
      English translation of the eighth (1920) edition. In the 1899 edition, Kraepelin
      acknowledged Weygandt for a new section on mixed manic-depressive states within
      the new integrated view of manic-depressive disorder. We provide biographical
      notes on Weygandt, a little-known but historically important figure, as well as
      the first English translation of his monograph and interpretive summaries of his
      findings. We also consider whether Weygandt's important insight that the same
      person could be both manic and depressed not only at different times but even at
      the same time served as an important stimulus to Kraepelin's unified manic
      depressive disorder concept, which survives as bipolar disorder a century later.

PMID- 12202453
TI  - How many bipolar mixed states are there?

PMID- 12202454
TI  - Optimal dosing of atypical antipsychotics in adults: a review of the current
      evidence.
AB  - This review describes dosing strategies used to optimize the beneficial effects
      of atypical antipsychotic medications. Differences between manufacturers'
      recommended dosing and actual clinical practice are reconciled using evidence
      from pivotal double-blind randomized registration studies, other randomized
      clinical trials, case series, and case reports. With clozapine and perhaps
      olanzapine, plasma levels are correlated with therapeutic response; with
      risperidone, plasma levels are not correlated with therapeutic response but may
      be related to the occurrence of extrapyramidal symptoms. Information related to
      optimal dosing of quetiapine and ziprasidone is more limited. In clinical
      practice, the mean daily dose of risperidone has decreased, whereas that for
      olanzapine is increasing. The percentage of patients receiving quetiapine at
      doses above the manufacturer's recommended maximum is higher than would be
      expected, further illustrating that dosing ranges established during registration
      studies may not reflect the needs of day-to-day practice.

PMID- 12202456
TI  - Resilience: a missing link in our understanding of survival.

PMID- 12202455
TI  - "Late-onset" borderline personality disorder: a life unraveling.

PMID- 12202457
TI  - Psychiatric aspects of breast cancer.

PMID- 12202458
TI  - Glycodelin: a major lipocalin protein of the reproductive axis with diverse
      actions in cell recognition and differentiation.
AB  - Glycodelin is a glycoprotein that belongs to the lipocalin superfamily. Depending
      on glycosylation, glycodelin appears in various isoforms. In the uterus,
      glycodelin-A is the major progesterone-regulated glycoprotein secreted into
      uterine luminal cavity by secretory/decidualized endometrial glands. The other
      tissues expressing glycodelin include fallopian tubes, ovary, breast, seminal
      vesicle, bone marrow, and eccrine glands. Glycodelin-A potently and dose
      dependently inhibits human sperm-egg binding, whereas differently glycosylated
      glycodelin-S from seminal plasma has no such effect. Absence of contraceptive
      glycodelin-A in the uterus during periovulatory midcycle is consistent with an
      open "fertile window." Glycodelin induced by local or systemic administration of
      progestogens may potentially reduce the fertilizing capacity of sperm in any
      phase of the menstrual cycle. Glycodelin also has immunosuppressive activity. Its
      high concentration at the fetomaternal interface may contribute to protection of
      the embryonic semiallograft. Besides being an epithelial differentiation marker,
      glycodelin appears to play a role in glandular morphogenesis, as transfection of
      glycodelin cDNA into a glycodelin-negative breast cancer cells resulted in
      formation of gland-like structures, restricted proliferation, and induction of
      other epithelial markers. These various properties, as well as the chemistry,
      biology, and clinical aspects of glycodelin, continue to be areas of active
      investigation reviewed in this communication.

PMID- 12202459
TI  - Molecular basis of combined pituitary hormone deficiencies.
AB  - Pituitary gland commitment from oral ectoderm occurs in response to inductive
      signals from the neuroepithelium of the ventral diencephalon. Invagination of the
      oral ectoderm leads to the creation of Rathke's pouch. Intensified cell
      proliferation within Rathke's pouch results in formation of the anterior
      pituitary lobe. Subsequently, highly differentiated cell types arise sequentially
      due to overlapping, but distinct, spatial and temporal patterns of signaling
      molecules and transcription factors. Mutations in some of the pituitary-specific
      transcription factors have been identified in patients with hypopituitarism,
      confirming the role of these factors in pituitary development.

PMID- 12202460
TI  - Bile acid regulation of gene expression: roles of nuclear hormone receptors.
AB  - Bile acids derived from cholesterol and oxysterols derived from cholesterol and
      bile acid synthesis pathways are signaling molecules that regulate cholesterol
      homeostasis in mammals. Many nuclear receptors play pivotal roles in the
      regulation of bile acid and cholesterol metabolism. Bile acids activate the
      farnesoid X receptor (FXR) to inhibit transcription of the gene for cholesterol
      7alpha-hydroxylase, and stimulate excretion and transport of bile acids.
      Therefore, FXR is a bile acid sensor that protects liver from accumulation of
      toxic bile acids and xenobiotics. Oxysterols activate the liver orphan receptors
      (LXR) to induce cholesterol 7alpha-hydroxylase and ATP-binding cassette family of
      transporters and thus promote reverse cholesterol transport from the peripheral
      tissues to the liver for degradation to bile acids. LXR also induces the sterol
      response element binding protein-1c that regulates lipogenesis. Therefore, FXR
      and LXR play critical roles in coordinate control of bile acid, cholesterol, and
      triglyceride metabolism to maintain lipid homeostasis. Nuclear receptors and bile
      acid/oxysterol-regulated genes are potential targets for developing drug
      therapies for lowering serum cholesterol and triglycerides and treating
      cardiovascular and liver diseases.

PMID- 12202461
TI  - Endocrinological disorders and celiac disease.
AB  - Celiac disease is a permanent intolerance to dietary gluten. Its well known
      features are abdominal symptoms, malabsorption of nutrients, and small-bowel
      mucosal inflammation with villous atrophy, which recover on a gluten-free diet.
      Diagnosis is challenging in that patients often suffer from subtle, if any,
      symptoms. The risk of clinically silent celiac disease is increased in various
      autoimmune conditions. The endocrinologist, especially, should maintain high
      suspicion and alertness to celiac disease, which is to be found in 2-5% of
      patients with insulin-dependent diabetes mellitus or autoimmune thyroid disease.
      Patients with multiple endocrine disorders, Addison's disease, alopecia, or
      hypophysitis may also have concomitant celiac disease. Similar heredity and
      proneness to autoimmune conditions are considered to be explanations for these
      associations. A gluten-free diet is essential to prevent celiac complications
      such as anemia, osteoporosis, and infertility. The diet may also be beneficial in
      the treatment of the underlying endocrinological disease; prolonged gluten
      exposure may even contribute to the development of autoimmune diseases. The
      diagnosis of celiac disease requires endoscopic biopsy, but serological screening
      with antiendomysial and antitissue transglutaminase antibody assays is an easy
      method for preliminary case finding. Celiac disease will be increasingly detected
      provided the close association with autoimmune endocrinological diseases is
      recognized.

PMID- 12202462
TI  - Guanylate cyclase activity and sperm function.
AB  - In species with external fertilization, the guanylate cyclase family is
      responsible for the long-distance interaction between gametes, as its activation
      allows sperm chemotaxis toward egg-derived substances, gamete encounter, and
      fertilization. In species with internal fertilization, guanylate cyclase
      activating substances, which are secreted by several tissues in the genital
      tracts of both sexes, deeply affect sperm motility, capacitation, and acrosomal
      reactivity, stimulating sperm metabolism and promoting the ability of the sperm
      to approach the oocyte, interact with it, and finally fertilize it. A complex
      system of intracellular pathways is activated by guanylate cyclase agonists in
      spermatozoa. Sperm motility appears to be affected mainly through an increase in
      intracellular cAMP, whereas the acrosome reaction depends more directly on cyclic
      GMP synthesis. Both cyclic nucleotides activate specific kinases and ion signals.
      A complex cross-talk between cAMP- and cyclic GMP-generating systems occurs,
      resulting in an upward shift in sperm function. Excessive amounts of certain
      guanylate cyclase activators might exert opposite, antireproductive effects,
      increasing the oxidative stress on sperm membranes. In view of the marked
      influence exerted by guanylate cyclase-activating substances on sperm function,
      it seems likely that guanylate cyclase activation or inhibition may represent a
      new approach for the diagnosis and treatment of male and/or female infertility.

PMID- 12202464
TI  - Meta-analyses of therapies for postmenopausal osteoporosis. I. Systematic reviews
      of randomized trials in osteoporosis: introduction and methodology.

PMID- 12202465
TI  - Meta-analyses of therapies for postmenopausal osteoporosis. II. Meta-analysis of
      alendronate for the treatment of postmenopausal women.
AB  - OBJECTIVE: To review the effect of alendronate on bone density and fractures in
      postmenopausal women. DATA SOURCE: We searched MEDLINE, EMBASE, Current Contents,
      and the Cochrane Controlled trials registry from 1980 to 1999, and we examined
      citations of relevant articles and proceedings of international meetings. STUDY
      SELECTION: We included 11 trials that randomized women to alendronate or placebo
      and measured bone density for at least 1 yr. DATA EXTRACTION: For each trial,
      three independent reviewers assessed the methodological quality and abstracted
      data. DATA SYNTHESIS: The pooled relative risk (RR) for vertebral fractures in
      patients given 5 mg or more of alendronate was 0.52 [95% confidence interval
      (CI), 0.43-0.65]. The RR of nonvertebral fractures in patients given 10 mg or
      more of alendronate was 0.51 (95% CI 0.38-0.69), an appreciably greater effect
      than for the 5 mg dose. We found a similar reduction in RR across nonvertebral
      fracture types; in particular, RR reductions for fractures traditionally thought
      to be "osteoporotic," such as hip and forearm, were very similar to RR reductions
      for "nonosteoporotic" fractures. Individual studies showed similar results,
      reflected in the P values of the test of heterogeneity (P = 0.99 for vertebral
      and 0.88 for nonvertebral fractures). Alendronate produced positive effects on
      the percentage change in bone density, which increased with both dose and time.
      After 3 yr of treatment with 10 mg of alendronate or more, the pooled estimate of
      the difference in percentage change between alendronate and placebo was 7.48%
      (95% CI 6.12-8.85) for the lumbar spine (2-3 yr), 5.60% (95% CI 4.80-6.39) for
      the hip (3-4 yr), 2.08% (95% CI 1.53-2.63) for the forearm (2-4 yr), and 2.73%
      (95% CI 2.27-3.20) for the total body (3 yr). Heterogeneity of the treatment
      effect of alendronate was not consistently explained by any of our a priori
      hypotheses; in particular, the effect was very similar in prevention and
      treatment studies. The pooled RR for discontinuing medication due to adverse
      effects for 5 mg or greater of alendronate was 1.15 (95% CI 0.93-1.42). The
      pooled RR for discontinuing medication due to gastro-intestinal (GI) side effects
      for 5 mg or greater was 1.03 (0.81-1.30, P = 0.83), and the pooled RR for GI
      adverse effects with continuation of medication was 1.03 (0.98 to 1.07) P = 0.23.
      CONCLUSIONS: Alendronate increases bone density in both early postmenopausal
      women and those with established osteoporosis while reducing the rate of
      vertebral fracture over 2-3 yr of treatment. Reductions in nonvertebral fractures
      are evident among postmenopausal women without prevalent fractures and have bone
      mineral density (BMD) levels below the World Health Organization threshold for
      osteoporosis. The impact on fractures appears consistent across all fracture
      types, casting doubt on traditional distinctions between osteoporotic and
      nonosteoporotic fractures.

PMID- 12202466
TI  - Meta-analyses of therapies for postmenopausal osteoporosis. III. Meta-analysis of
      risedronate for the treatment of postmenopausal osteoporosis.
AB  - OBJECTIVE: To review the effect of risedronate on bone density and fractures in
      postmenopausal women. DATA SOURCES: We searched MEDLINE from 1966 to the end of
      2000 and examined citations of relevant articles and the proceedings of
      international osteoporosis meetings. STUDY SELECTION: We included eight
      randomized, placebo-controlled trials of postmenopausal women receiving
      risedronate or placebo with a follow-up of at least one year and providing data
      on bone density or fracture rate. DATA EXTRACTION: For each trial, two
      independent reviewers assessed the methodological quality and abstracted data.
      DATA SYNTHESIS: The major methodological limitation of the trials was the loss to
      follow-up, which was over 20% in most trials and over 35% in the largest study.
      However, the magnitude of the treatment effect was unrelated to loss to follow
      up, and in one of the largest trials, more high-risk patients were lost to follow
      up in the control than in the treatment group. The pooled relative risk (RR) for
      vertebral fractures in women given 2.5 mg or more of risedronate was 0.64 [95%
      confidence interval (CI) 0.54, 0.77]. The pooled RR of nonvertebral fractures in
      patients given 2.5 mg or more of risedronate was 0.73 (95% CI 0.61, 0.87).
      Risedronate produced positive effects on the percentage change in bone density of
      the lumbar spine, combined forearm, and femoral neck that were generally larger
      with the 5-mg daily dose than with cyclical administration or the 2.5-mg dose.
      The pooled estimate of the difference in percentage change between 5 mg
      risedronate and placebo after the final year of treatment (1.5-3 yr) was 4.54%
      (95% CI 4.12, 4.97) for the lumbar spine, and 2.75% (95% CI 2.32, 3.17) at the
      femoral neck. CONCLUSIONS: Risedronate substantially reduces the risk of both
      vertebral and nonvertebral fractures. This fracture reduction is accompanied by
      an increase in bone density of the lumbar spine and femoral neck in both early
      postmenopausal women and those with established osteoporosis.

PMID- 12202467
TI  - Meta-analyses of therapies for postmenopausal osteoporosis. IV. Meta-analysis of
      raloxifene for the prevention and treatment of postmenopausal osteoporosis.
AB  - OBJECTIVE: To review the effect of raloxifene on bone density and fractures in
      postmenopausal women. DATA SOURCE: We searched MEDLINE from 1966 to 2000 and
      examined citations of relevant articles and the proceedings of international
      osteoporosis meetings. STUDY SELECTION: We included seven trials that randomized
      women to raloxifene or placebo, with both groups receiving similar calcium and
      vitamin D supplementation, and measured bone density for at least one year. DATA
      EXTRACTION: For each trial, three independent reviewers abstracted the data and
      assessed the methodological quality using a validated tool. DATA SYNTHESIS: Data
      from one large dominating trial suggest a reduction in vertebral fractures with a
      relative risk (RR) of 0.60 [95% confidence interval (CI) 0.50-0.70, P < 0.01].
      The RR of nonvertebral fractures in patients given 60 mg or more of raloxifene in
      the larger study was 0.92 (95% CI 0.79-1.07, P = 0.27). Raloxifene resulted in
      positive effects on the percentage change in bone density, which increased over
      time and was independent of dose. At the final year, point estimates and 95% CIs
      for the differences in percent change in bone density (95% CI) between raloxifene
      and placebo groups were 1.33 (95% CI 0.37-2.30) for total body, 2.51 (95% CI 2.21
      2.82) for lumbar spine, 2.05 (95% CI 0.71-3.39) for combined forearm, and 2.11
      (95% CI 1.68-2.53) for combined hip (P < 0.01 at all four sites). Results were
      similar across studies, and formal tests of heterogeneity did not approach
      conventional statistical significance. Raloxifene slightly increased rates of
      withdrawal from therapy as a result of adverse effects (RR 1.15, 95% CI 1.00
      1.33, P = 0.05). The pooled RR was significant for hot flashes 1.46 (95% CI 1.23
      1.74, P < 0.01) and nonsignificant for leg cramps 1.64 (95% CI 0.84-3.20, P =
      0.15). CONCLUSION: Raloxifene increases bone density, and the effect increases
      over 2 yr. The data suggest a positive impact of raloxifene on vertebral
      fractures. There was little effect of raloxifene on nonvertebral fractures.

PMID- 12202468
TI  - Meta-analyses of therapies for postmenopausal osteoporosis. V. Meta-analysis of
      the efficacy of hormone replacement therapy in treating and preventing
      osteoporosis in postmenopausal women.
AB  - OBJECTIVE: To review the effect of hormone replacement therapy (HRT) on bone
      density and fractures in postmenopausal women. DATA SOURCE: We searched MEDLINE
      and EMBASE from 1966 to 1999, the Cochrane Controlled Register, citations of
      relevant articles, and proceedings of international meetings for eligible
      randomized controlled trials. We contacted osteoporosis investigators to identify
      additional studies, and primary authors for unpublished data. STUDY SELECTION: We
      included 57 studies that randomized postmenopausal women to HRT or a control
      (placebo or calcium/vitamin D) and were of at least 1 yr in duration. Seven of
      these studies reported fractures. DATA ABSTRACTION: For each study, three
      independent reviewers assessed the methodological quality and abstracted the
      data. DATA SYNTHESIS: HRT showed a trend toward reduced incidence of vertebral
      fractures [relative risk (RR) 0.66, 95% confidence interval (CI) 0.41-1.07; 5
      trials] and nonvertebral fractures (RR 0.87, 95% CI 0.71-1.08; 6 trials). HRT had
      a consistent effect on bone mineral density (BMD) at all sites. The difference
      between HRT and control in the percent change in bone density at 2 yr was 6.76
      (5.83, 7.89; 21 trials) at the lumbar spine and 4.53 (3.68, 5.36; 14 trials) and
      4.12 (3.45, 4.80; 9 trials) at the forearm and femoral neck, respectively.
      CONCLUSIONS: HRT has a consistent, favorable and large effect on bone density at
      all sites. The data show a nonsignificant trend toward a reduced incidence in
      vertebral and nonvertebral fractures.

PMID- 12202469
TI  - Meta-analyses of therapies for postmenopausal osteoporosis. VI. Meta-analysis of
      calcitonin for the treatment of postmenopausal osteoporosis.
AB  - OBJECTIVE: To review the effect of calcitonin on bone density and fractures in
      postmenopausal women. DATA SOURCE: We searched MEDLINE and EMBASE from 1966 to
      2000 and examined citations of relevant articles and the proceedings of
      international osteoporosis meetings. We contacted osteoporosis investigators to
      identify additional studies and primary authors for unpublished data. STUDY
      SELECTION: We included 30 studies that randomized women to calcitonin or an
      alternative (placebo or calcium and/or vitamin D) and measured bone density or
      fracture incidence for at least 1 yr. DATA EXTRACTION: For each trial, three
      independent reviewers assessed the methodological quality and abstracted data.
      DATA SYNTHESIS: Calcitonin reduced the incidence of vertebral fractures, with a
      pooled relative risk (RR) of 0.46 [95% confidence interval (CI) 0.25-0.87, P =
      0.02, n = 1404, 4 trials]. However, the RR from the one relatively large
      randomized controlled trial (RCT) was 0.79 (95% CI 0.62-1.00, P = 0.05, n =
      1108). For nonvertebral fractures, the pooled RR was 0.52 (95% CI 0.22-1.23, P =
      0.14, n = 1481, 3 trials). Once again, the single large trial showed a less
      impressive effect than the smaller trials (RR 0.80, 95% CI 0.59-1.09, P = 0.16, n
      = 1245). For bone density of the lumbar spine, the pooled weekly dose of 250 to
      2800 IU per week resulted in significant increase in the weighted mean difference
      (WMD) of 3.74 (2.04-5.43, P < 0.01, n = 2260, 24 trials). The combined forearm
      showed a similar effect, with a WMD of 3.02 (95% CI 0.98-5.07, P < 0.01, n = 468,
      9 trials). At the femoral neck, the pooled weighted mean difference showed a
      nonsignificant trend toward benefit, WMD 3.80 (95% CI -0.32-7.91, P = 0.07, 9
      trials, n = 513). Methodologically weaker studies tended to show greater effects
      on bone density, and the lumbar spine results suggested the possibility of
      publication bias. CONCLUSIONS: Calcitonin likely increases bone density in
      postmenopausal women predominantly at the lumbar spine and forearm for weekly
      doses of greater than 250 IU, although the true effect may be smaller than the
      pooled estimate would suggest. Calcitonin likely reduces the risk of vertebral
      fracture; its effect on nonvertebral fracture remains uncertain.

PMID- 12202470
TI  - Meta-analyses of therapies for postmenopausal osteoporosis. VII. Meta-analysis of
      calcium supplementation for the prevention of postmenopausal osteoporosis.
AB  - OBJECTIVE: To summarize controlled trials examining the effect of calcium on bone
      density and fractures in postmenopausal women. DATA SOURCE: We searched MEDLINE
      and EMBASE up to 1998 and the Cochrane Controlled Register up to 2000, and we
      examined citations of relevant articles and proceedings of international
      meetings. We contacted osteoporosis investigators to identify additional studies,
      and primary authors for unpublished data. STUDY SELECTION: We included 15 trials
      (1806 patients) that randomized postmenopausal women to calcium supplementation
      or usual calcium intake in the diet and reported bone mineral density of the
      total body, vertebral spine, hip, or forearm, or recorded the number of
      fractures, and followed patients for at least 1 yr. DATA EXTRACTION: For each
      trial, three independent reviewers assessed the methodological quality and
      extracted data. DATA SYNTHESIS: We found calcium to be more effective than
      placebo in reducing rates of bone loss after two or more years of treatment. The
      pooled difference in percentage change from baseline was 2.05% [95% confidence
      interval (CI) 0.24-3.86] for total body bone density, 1.66% (95% CI 0.92-2.39)
      for the lumbar spine, 1.64% (95% CI 0.70-2.57) for the hip, and 1.91% (95% CI
      0.33-3.50) for the distal radius. The relative risk (RR) of fractures of the
      vertebrae was 0.77, with a wide CI (95% CI 0.54-1.09); the RR for nonvertebral
      fractures was 0.86 (95% CI 0.43-1.72). CONCLUSIONS: Calcium supplementation alone
      has a small positive effect on bone density. The data show a trend toward
      reduction in vertebral fractures, but do not meaningfully address the possible
      effect of calcium on reducing the incidence of nonvertebral fractures.

PMID- 12202471
TI  - Meta-analyses of therapies for postmenopausal osteoporosis. VIII: Meta-analysis
      of the efficacy of vitamin D treatment in preventing osteoporosis in
      postmenopausal women.
AB  - OBJECTIVE: To review the effect of vitamin D on bone density and fractures in
      postmenopausal women. DATA SOURCE: We searched MEDLINE and EMBASE from 1966 to
      1999 and examined citations of relevant articles and proceedings of international
      meetings. We contacted osteoporosis investigators and primary authors to identify
      additional studies and to obtain unpublished data. STUDY SELECTION: We included
      25 trials that randomized women to standard or hydroxylated vitamin D with or
      without calcium supplementation or a control and measured bone density or
      fracture incidence for at least 1 yr. DATA EXTRACTION: For each trial, three
      independent reviewers assessed the methodological quality and abstracted data.
      DATA SYNTHESIS: Vitamin D reduced the incidence of vertebral fractures [relative
      risk (RR) 0.63, 95% confidence interval (CI) 0.45-0.88, P < 0.01) and showed a
      trend toward reduced incidence of nonvertebral fractures (RR 0.77, 95% CI 0.57
      1.04, P = 0.09). Most patients in the trials that evaluated vertebral fractures
      received hydroxylated vitamin D, and most patients in the trials that evaluated
      nonvertebral fractures received standard vitamin D. Hydroxylated vitamin D had a
      consistently larger impact on bone density than did standard vitamin D. For
      instance, total body differences in percentage change between hydroxylated
      vitamin D and control were 2.06 (0.72, 3.40) and 0.40 (-0.25, 1.06) for standard
      vitamin D. At the lumbar spine and forearm sites, hydroxylated vitamin D doses
      above 50 microg yield larger effects than lower doses. Vitamin D resulted in an
      increased risk of discontinuing medication in comparison to control as a result
      of either symptomatic adverse effects or abnormal laboratory results (RR 1.37,
      95% CI 1.01-1.88), an effect that was similar in trials of standard and
      hydroxylated vitamin D. CONCLUSIONS: Vitamin D decreases vertebral fractures and
      may decrease nonvertebral fractures. The available data are uninformative
      regarding the relative effects of standard and hydroxylated vitamin D.

PMID- 12202472
TI  - Meta-analyses of therapies for postmenopausal osteoporosis. IX: Summary of meta
      analyses of therapies for postmenopausal osteoporosis.
AB  - This section summarizes the results of the seven systematic reviews of
      osteoporosis therapies published in this series [calcium, vitamin D, hormone
      replacement therapy (HRT), alendronate, risedronate, raloxifene, and calcitonin]
      and systematic reviews of etidronate and fluoride we have published elsewhere. We
      highlight the methodological strengths and weaknesses of the individual studies,
      and summarize the effects of treatments on the risk of vertebral and nonvertebral
      fractures and on bone density, including effects in different patient subgroups.
      We provide an estimate of the expected impact of antiosteoporosis interventions
      in prevention and treatment populations using the number needed to treat (NNT) as
      a reference. In addition to the evidence, judgements about the relative weight
      that one places on weaker and stronger evidence, attitudes toward uncertainty,
      circumstances of patients' and societal values or preferences will, and should,
      play an important role in decision-making regarding anti-osteoporosis therapy.

PMID- 12202473
TI  - The Endocrine Society Awards.

PMID- 12202474
TI  - The Endocrine Society 2002 Annual Awards.

PMID- 12202476
TI  - Role of N-linked oligosaccharide flexibility in mannose phosphorylation of
      lysosomal enzyme cathepsin L.
AB  - Mannose phosphorylation of N-linked oligosaccharides by UDP-GlcNAc:lysosomal
      enzyme N-acetylglucosamine-1-phosphotransferase is a key step in the targeting of
      lysosomal enzymes in mammalian cells and tissues. The selectivity of this process
      is determined by lysine-based phosphorylation signals shared by lysosomal enzymes
      of diverse structure and function. By introducing new glycosylation sites at
      several locations on the surface of mouse procathepsin L and modeling
      oligosaccharide conformations for sites that are phosphorylated, it was shown
      that the inherent flexibility of N-linked oligosaccharides can account for the
      specificity of the transferase for oligosaccharides at different locations on the
      protein. By using this approach, the physical relationship between the lysine
      based signal and the site of phosphorylation of mannose residues was determined.
      The analysis also revealed the existence of additional independent lysine-based
      phosphorylation signals on procathepsin L, which account for the low level of
      phosphorylation observed when the primary Lys-54/Lys-99 signal is ablated.
      Mutagenesis of residues that surround Lys-54 and Lys-99 and demonstration of
      mannose phosphorylation of a glycosylated derivative of green fluorescent protein
      provide strong evidence that the cathepsin L phosphorylation signal is a simple
      structure composed of as few as two well placed lysine residues.

PMID- 12202477
TI  - P21 functions to maintain quiescence of p27-deficient hepatocytes.
AB  - Hepatocytes rarely proliferate in the healthy adult liver. We explored the roles
      of the cyclin kinase inhibitors p21 and p27 in maintaining hepatocyte quiescence.
      p27 is expressed throughout the wild-type liver, but the related protein p21 was
      not detected. However, p21 was detected in livers of p27-deficient mice.
      Increased p21 protein levels did not result from an increase in p21 mRNA
      expression, indicating that p21 expression is regulated post-transcriptionally.
      p21 protein levels increased in cultured primary hepatocytes treated with the
      proteasome inhibitor MG132 and cycloheximide, indicating that p21 expression is
      regulated at the level of protein stability in liver cells. Although increased
      expression of cyclin-dependent kinase (Cdk) 4, Cdk2, and proliferating cell
      nuclear antigen was detected in p27-deficient livers, increased hepatocyte
      proliferation was detected only in livers of mice deficient for both p21 and p27.
      In p27-deficient livers, p21 was found in complexes with Cdk2 and CdK4 and can
      compensate for the absence of p27. Our data indicate that cyclin kinase inhibitor
      activity is important for maintaining hepatocyte quiescence in the adult liver.
      Significant increases in p21 were detected in multiple tissues of mature p27
      deficient mice compared with wild-type mice, suggesting that the ability of p21
      to functionally substitute for p27 is not liver-specific.

PMID- 12202478
TI  - Non-malignant and tumor-derived cells differ in their requirement for p27Kip1 in
      transforming growth factor-beta-mediated G1 arrest.
AB  - Transforming growth factor beta (TGF-beta) induces G(1) arrest in susceptible
      cells by multiple mechanisms that inhibit the G(1) cyclin-dependent kinases
      (Cdks), including Cdk2, Cdk4, and Cdk6. TGF-beta treatment of early passage
      finite lifespan human mammary epithelial cells (HMECs) led to an accumulation of
      p27(Kip1) in cyclin E1-Cdk2 complexes and kinase inhibition. The requirement for
      p27 in the G(1) arrest by TGF-beta was assessed by transfection of antisense p27
      (ASp27) oligonucleotides into TGF-beta-treated HMECs. Despite a reduction in
      total and cyclin E-Cdk2 bound p27 after ASp27 transfection, HMECs remained
      arrested in the G(1) phase. Maintenance of the G(1) arrest was accompanied by
      increased association of the Cdk inhibitor p21(WAF-1/Cip-1) and the
      retinoblastoma family member p130(Rb2) in cyclin E1-Cdk2 complexes along with
      kinase inhibition. In contrast to the findings in HMECs, p27 was essential for
      G(1) arrest by TGF-beta in two tumor-derived lines. ASp27 transfection into two
      TGF-beta-responsive, cancer-derived lines was not associated with increased
      compensatory binding of p21 and p130 to cyclin E1-Cdk2, and these cell lines
      failed to maintain G(1) arrest despite the continued presence of TGF-beta.
      Progressive cell cycle deregulation leading to impaired checkpoint controls
      during malignant tumor progression may alter the role of p27 from a redundant to
      an essential inhibitor of G(1)-to-S phase progression.

PMID- 12202479
TI  - The modulation of mitochondrial nitric-oxide synthase activity in rat brain
      development.
AB  - Different mitochondrial nitric-oxide synthase (mtNOS) isoforms have been
      described in rat and mouse tissues, such as liver, thymus, skeletal muscle, and
      more recently, heart and brain. The modulation of these variants by thyroid
      status, hypoxia, or gene deficiency opens a broad spectrum of mtNOS-dependent
      tissue-specific functions. In this study, a new NOS variant is described in rat
      brain with an M(r) of 144 kDa and mainly localized in the inner mitochondrial
      membrane. During rat brain maturation, the expression and activity of mtNOS were
      maximal at the late embryonic stages and early postnatal days followed by a
      decreased expression in the adult stage (100 +/- 9 versus 19 +/- 2 pmol of
      [(3)H]citrulline/min/mg of protein, respectively). This temporal pattern was
      opposite to that of the cytosolic 157-kDa nNOS protein. Mitochondrial redox
      changes followed the variations in mtNOS activity: mtNOS-dependent production of
      hydrogen peroxide was maximal in newborns and decreased markedly in the adult
      stage, thus reflecting the production and utilization of mitochondrial matrix
      nitric oxide. Moreover, the activity of brain Mn-superoxide dismutase followed a
      developmental pattern similar to that of mtNOS. Cerebellar granular cells
      isolated from newborn rats and with high mtNOS activity exhibited maximal
      proliferation rates, which were decreased by modifying the levels of either
      hydrogen peroxide or nitric oxide. Altogether, these findings support the notion
      that a coordinated modulation of mtNOS and Mn-superoxide dismutase contributes to
      establish the rat brain redox status and participate in the normal physiology of
      brain development.

PMID- 12202480
TI  - Novel combinatorial interactions of GATA-1, PU.1, and C/EBPepsilon isoforms
      regulate transcription of the gene encoding eosinophil granule major basic
      protein.
AB  - GATA-1 and the ets factor PU.1 have been reported to functionally antagonize one
      another in the regulation of erythroid versus myeloid gene transcription and
      development. The CCAAT enhancer binding protein epsilon (C/EBPepsilon) is
      expressed as multiple isoforms and has been shown to be essential to myeloid
      (granulocyte) terminal differentiation. We have defined a novel synergistic, as
      opposed to antagonistic, combinatorial interaction between GATA-1 and PU.1, and a
      unique repressor role for certain C/EBPepsilon isoforms in the transcriptional
      regulation of a model eosinophil granulocyte gene, the major basic protein (MBP).
      The eosinophil-specific P2 promoter of the MBP gene contains GATA-1, C/EBP, and
      PU.1 consensus sites that bind these factors in nuclear extracts of the
      eosinophil myelocyte cell line, AML14.3D10. The promoter is transactivated by
      GATA-1 alone but is synergistically transactivated by low levels of PU.1 in the
      context of optimal levels of GATA-1. The C/EBPepsilon(27) isoform strongly
      represses GATA-1 activity and completely blocks GATA-1/PU.1 synergy. In vitro
      mutational analyses of the MBP-P2 promoter showed that both the GATA-1/PU.1
      synergy, and repressor activity of C/EBPepsilon(27) are mediated via protein
      protein interactions through the C/EBP and/or GATA-binding sites but not the PU.1
      sites. Co-immunoprecipitations using lysates of AML14.3D10 eosinophils show that
      both C/EBPepsilon(32/30) and epsilon(27) physically interact in vivo with PU.1
      and GATA-1, demonstrating functional interactions among these factors in
      eosinophil progenitors. Our findings identify novel combinatorial protein-protein
      interactions for GATA-1, PU.1, and C/EBPepsilon isoforms in eosinophil gene
      transcription that include GATA-1/PU.1 synergy and repressor activity for
      C/EBPepsilon(27).

PMID- 12202481
TI  - Mice expressing the human CYP7A1 gene in the mouse CYP7A1 knock-out background
      lack induction of CYP7A1 expression by cholesterol feeding and have increased
      hypercholesterolemia when fed a high fat diet.
AB  - Cholesterol 7alpha-hydroxylase (CYP7A1) catalyzes the rate-limiting step in the
      pathway responsible for the formation of the majority of bile acids.
      Transcription of the gene is regulated by the size of the bile acid pool and
      dietary and hormonal factors. The farnesoid X receptor and the liver X receptor
      (LXR) are responsible for regulation by bile acids and cholesterol, respectively.
      To study the effects of dietary cholesterol and fat upon expression of the human
      CYP7A1 gene, mice were generated by crossing transgenic mice carrying the human
      CYP7A1 gene with mice that were homozygous knock-outs (CYP7A1(-/-)). The mice
      (mCYP7A1(-/-)/hCYP7A1) expressed the human gene at much higher levels than did
      the transgenics bred in the wild-type background. A diet containing 1% cholic
      acid reduced the expression of the human gene in mCYP7A1(-/-)/hCYP7A1 mice to
      undetectable levels. Cholestyramine (5%) increased the level of expression of the
      human gene and the mouse gene. Thus, farnesoid X receptor-mediated regulation was
      preserved. A diet containing 2% cholesterol increased expression of the mouse
      gene in wild-type mice, but it did not affect expression of the human gene in
      mCYP7A1(-/-)/hCYP7A1 mice. None of the diets altered the serum cholesterol or
      triglyceride levels in these mice; 1% cholic acid caused a redistribution of
      cholesterol from the high density lipoprotein to the low density lipoprotein
      density in the humanized mice but not in wild-type mice. A diet containing 30%
      saturated fat and 2% cholesterol caused a decrease in CYP7A1 levels in mCYP7A1(-/
      )/hCYP7A1 mice. The serum cholesterol levels rose in all mice fed this diet. The
      increase was greater in the mCYP7A1(-/-)/hCYP7A1 mice. Together, these data
      suggest that the lack of an LXR element in the region from -56 to -49 of the
      human CYP7A1 promoter may account for some of the differences in response to
      diets between humans and rodents.

PMID- 12202482
TI  - Regulation of TRKB surface expression by brain-derived neurotrophic factor and
      truncated TRKB isoforms.
AB  - Brain-derived neurotrophic factor (BDNF) signaling through its receptor TRKB
      modulates survival, differentiation, and activity of neurons. BDNF activates TRKB
      on the cell surface, which leads to the initiation of intracellular signaling
      cascades and different biological responses in neurons. Neuronal activity has
      been shown to regulate TRKB levels on the plasma membrane of neurons, but little
      is known about other factors affecting TRKB surface expression levels. We report
      here that BDNF regulates the cell surface levels of transfected or endogenously
      expressed full-length TRKB, depending on the exposure time in neuroblastoma cells
      and primary hippocampal neurons. BDNF rapidly increases TRKB surface expression
      levels in seconds, whereas treatment of cells with BDNF for a longer time
      (minutes to hours) leads to decreased TRKB surface levels. Coexpression of the
      full-length TRKB together with the truncated TRKB.T1 isoform results in decreased
      levels of full-length TRKB on the cell surface. This effect is specific to the T1
      isoform, because coexpression of a kinase-dead TRKB mutant or another kinase
      domain-lacking TRKB form, truncated T-Shc, leads to increased TRKB surface
      levels. Our results suggest that regulation of TRKB surface expression levels by
      different factors is tightly controlled by complex mechanisms in active neurons.

PMID- 12202483
TI  - Autocatalytic cleavage of ADAMTS-4 (Aggrecanase-1) reveals multiple
      glycosaminoglycan-binding sites.
AB  - ADAMTS-4, also referred to as aggrecanase-1, is a glutamyl endopeptidase capable
      of generating catabolic fragments of aggrecan analogous to those released from
      articular cartilage during degenerative joint diseases such as osteoarthritis.
      Efficient aggrecanase activity requires the presence of sulfated
      glycosaminoglycans (GAGs) attached to the aggrecan core protein, implying the
      contribution of substrate recognition/binding site(s) to ADAMTS-4 activity. In
      the present study, we demonstrate that full-length ADAMTS-4 (M(r) approximately
      68,000) undergoes autocatalytic C-terminal truncation to generate two discrete
      isoforms (M(r) approximately 53,000 and M(r) approximately 40,000), which exhibit
      a marked reduction in affinity of binding to sulfated GAGs. C-terminal sequencing
      and mass analyses revealed that the GAG-binding thrombospondin type I motif was
      retained following autocatalysis, indicating that sites present in the C-terminal
      cysteine (cys)-rich and/or spacer domains also effect binding of full-length
      ADAMTS-4 to sulfated GAGs. Binding-competition experiments conducted using native
      and deglycosylated aggrecan provided direct evidence for interaction of the
      ADAMTS-4 cysteine-rich/spacer domains with aggrecan GAGs. Furthermore, synthetic
      peptides mimicking putative (consensus) GAG-binding sequences located within the
      ADAMTS-4 cysteine-rich and spacer domains competitively blocked binding of
      sulfated GAGs to full-length ADAMTS-4, thereby identifying multiple GAG-binding
      sites, which may contribute to the regulation of ADAMTS-4 function.

PMID- 12202484
TI  - Proteomic analysis of a detergent-resistant membrane skeleton from neutrophil
      plasma membranes.
AB  - Plasma membranes are organized into functional domains both by liquid-ordered
      packing into "lipid rafts," structures that resist Triton extraction, and by
      attachments to underlying cytoskeletal proteins in assemblies called "membrane
      skeletons." Although the actin cytoskeleton is implicated in many lipid raft
      mediated signaling processes, little is known about the biochemical basis for
      actin involvement. We show here that a subset of plasma membrane skeleton
      proteins from bovine neutrophils co-isolates with cholesterol-rich, detergent
      resistant membrane fragments (DRMs) that exhibit a relatively high buoyant
      density in sucrose (DRM-H; d approximately 1.16 g/ml). By using matrix-assisted
      laser desorption/ionization time of flight and tandem mass spectrometry, we
      identified 19 major DRM-H proteins. Membrane skeleton proteins include fodrin
      (nonerythroid spectrin), myosin-IIA, myosin-IG, alpha-actinin 1, alpha-actinin 4,
      vimentin, and the F-actin-binding protein, supervillin. Other DRM-H components
      include lipid raft-associated integral membrane proteins (stomatin, flotillin 1,
      and flotillin 2), extracellular surface-bound and glycophosphatidylinositol
      anchored proteins (IgM, membrane-type 6 matrix metalloproteinase), and
      intracellular dually acylated signaling proteins (Lyn kinase, Galpha(i-2)).
      Consistent with cytoskeletal association, most DRM-H-associated flotillin 2, Lyn,
      and Galpha(i-2) also resist extraction with 0.1 m octyl glucoside. Supervillin,
      myosin-IG, and myosin-IIA resist extraction with 0.1 m sodium carbonate, a
      treatment that removes all detectable actin, suggesting that these cytoskeletal
      proteins are proximal to the DRM-H bilayer. Binding of supervillin to the DRM-H
      fragments is confirmed by co-immunoaffinity purification. In spreading
      neutrophils, supervillin localizes with F-actin in cell extensions and in
      discrete basal puncta that partially overlap with Galpha(i) staining. We suggest
      that the DRM-H fraction represents a membrane skeleton-associated subset of
      leukocyte signaling domains.

PMID- 12202485
TI  - Cytoskeletal changes in hypoxic pulmonary endothelial cells are dependent on MAPK
      activated protein kinase MK2.
AB  - Exposure to hypoxia causes structural changes in the endothelial cell layer that
      alter its permeability and its interaction with leukocytes and platelets. One of
      the well characterized cytoskeletal changes in response to stress involves the
      reorganization of the actin cytoskeleton and the formation of stress fibers. This
      report describes cytoskeletal changes in pulmonary microvascular endothelial
      cells in response to hypoxia and potential mechanisms involved in this process.
      The hypoxia-induced actin redistribution appears to be mediated by components
      downstream of MAPK p38, which is activated in pulmonary endothelial cells in
      response to hypoxia. Our results indicate that kinase MK2, which is a substrate
      of p38, becomes activated by hypoxia, leading to the phosphorylation of one of
      its substrates, HSP27. Because HSP27 phosphorylation is known to alter actin
      distribution in response to other stimuli, we postulate that it also causes the
      actin redistribution observed in hypoxia. This notion is supported by the
      observations that similar actin redistribution occurs in cells overexpressing
      constitutively active MK2 or phosphomimicking HSP27 mutant. Overexpressing
      dominant negative MK2 blocks the effects of hypoxia on the actin cytoskeleton.
      Taken together these results indicate that hypoxia stimulates the p38-MK2-HSP27
      pathway leading to significant alteration in the actin cytoskeleton.

PMID- 12202486
TI  - Transactivation of the epidermal growth factor receptor in colonic epithelial
      cells by carbachol requires extracellular release of transforming growth factor
      alpha.
AB  - We have shown previously that the muscarinic agonist, carbachol (CCh),
      transactivates the epidermal growth factor receptor (EGFr) via calmodulin, Pyk-2,
      and Src kinase activation. EGFr phosphorylation causes extracellular signal
      regulated kinase (ERK) activation and inhibits CCh-stimulated chloride secretion
      across intestinal epithelial cells. Here we investigated whether CCh-stimulated
      EGFr transactivation involves EGFr ligand release. Pre-incubation of T(84) cell
      monolayers with a neutralizing antibody to the EGFr ligand binding domain
      decreased CCh-induced phosphorylation of EGFr and ERK. CCh-stimulated efflux of
      (86)Rb+ from T(84) cell monolayers, which parallels changes in chloride
      secretion, was potentiated by anti-EGFr pre-incubation. Anti-EGFr did not reduce
      CCh-stimulated Pyk-2 phosphorylation. Co-incubation with the Src kinase inhibitor
      PP2 and anti-EGFr had an additive inhibitory effect on CCh-induced ERK
      phosphorylation greater than either inhibitor alone. CCh caused the basolateral
      release of transforming growth factor alpha (TGF-alpha) into T(84) cell bathing
      media. A metalloproteinase inhibitor, WAY171318, reduced CCh-induced
      phosphorylation of ERK and completely blocked EGFr phosphorylation and TGF-alpha
      release. We conclude that CCh-stimulated EGFr transactivation and subsequent ERK
      activation, a pathway that limits CCh-induced chloride secretion, is mediated by
      metalloproteinase-dependent extracellular release of TGF-alpha and intracellular
      Src activation. These findings have important implications for our understanding
      of the role of growth factors in regulating epithelial ion secretion.

PMID- 12202487
TI  - Differential sensitivity between Fks1p and Fks2p against a novel beta -1,3-glucan
      synthase inhibitor, aerothricin3 [corrected].
AB  - Fks1p and Fks2p are catalytic subunits of beta-1,3-glucan synthase, which
      synthesize beta-1,3-glucan, a main component of the cell wall in Saccharomyces
      cerevisiae. Although Fks1p and Fks2p are highly homologous, sharing 88.1%
      identity, it has been shown that Fks2p is more sensitive than Fks1p to one of
      echinocandin derivatives, which inhibits beta-1,3-glucan synthase activity. Here
      we show a similar differential sensitivity between Fks1p and Fks2p to a novel
      beta-1,3-glucan synthase inhibitor, aerothricin3 [corrected]. To investigate the
      molecular mechanism of this differential sensitivity, we constructed a series of
      chimeric genes of FKSs and examined their sensitivity to aerothricin3
      [corrected]. As a result, it was shown that a region around the fourth
      extracellular domain of Fks2p, containing 10 different amino acid residues from
      those of Fks1p, provided Fks1p aerothricin3 [corrected] sensitivity when the
      region was replaced with a corresponding region of Fks1p. In order to identify
      essential amino acid residues responsible for the sensitivity, each of the 10 non
      conserved amino acids of Fks1p was substituted into the corresponding amino acid
      of Fks2p by site-directed mutagenesis. Surprisingly, only one amino acid
      substitution of Fks1p (K1336I) conferred Fks1p hypersensitivity to aerothricin3
      [corrected]. On the other hand, reverse substitution of the corresponding amino
      acid of Fks2p (I1355K) resulted in loss of hypersensitivity to aerothricin3
      [corrected]. These results suggest that the 1355th isoleucine of Fks2p plays a
      key role in aerothricin3 [corrected] sensitivity.

PMID- 12202488
TI  - The calcium sensor protein visinin-like protein-1 modulates the surface
      expression and agonist sensitivity of the alpha 4beta 2 nicotinic acetylcholine
      receptor.
AB  - The calcium sensor protein visinin-like protein-1 (VILIP-1) was isolated from a
      brain cDNA yeast two-hybrid library using the large cytoplasmic domain of the
      alpha4 subunit as a bait. VILIP-1 is a myristoylated calcium sensor protein that
      contains three functional calcium binding EF-hand motifs. The alpha4 subunit
      residues 302-339 were found to be essential for the interaction with VILIP-1.
      VILIP-1 coimmunopurified with detergent-solubilized recombinant alpha4beta2
      acetylcholine receptors (AChRs) expressed in tsA201 cells and with native alpha4
      AChRs isolated from brain. Coexpression of VILIP-1 with recombinant alpha4beta2
      AChRs up-regulated their surface expression levels approximately 2-fold and
      increased their agonist sensitivity to acetylcholine approximately 3-fold. The
      modulation of the recombinant alpha4beta2 AChRs by VILIP-1 was attenuated in
      VILIP-1 mutants that lacked the ability to be myristoylated or to bind calcium.
      Collectively, these results suggest that VILIP-1 represents a novel modulator of
      alpha4beta2 AChRs that increases their surface expression levels and agonist
      sensitivity in response to changes in the intracellular levels of calcium.

PMID- 12202489
TI  - c-Myc augments the apoptotic activity of cytosolic death receptor signaling
      proteins by engaging the mitochondrial apoptotic pathway.
AB  - Activation of c-Myc sensitizes cells to apoptosis induction by ligand-activated
      death receptors. Such sensitization to death receptors by oncogenes may well be
      the mechanism underlying tumor cell sensitivity to tumor necrosis factor (TNF) or
      TNF-related apoptosis-inducing ligand (TRAIL). The mechanism by which this c-Myc
      induced sensitization occurs is unclear but could involve modulation of
      expression of death receptors or their ligands or potentiation of the sensitivity
      of mitochondria to release pro-apoptotic effectors such as holocytochrome c.
      Here, we show that ectopic expression of the death receptor signaling protein RIP
      (receptor-interactive protein) triggers apoptosis via a FAS-associated death
      domain protein (FADD) and caspase 8-dependent pathway. Induction of apoptosis by
      this intracellular activation of the death receptor signaling pathway is
      significantly augmented by c-Myc expression. Moreover, c-Myc expression strongly
      promotes the potential of RIP to induce cytochrome c release from mitochondria.
      This implicates the mitochondrial apoptotic pathway in this synergy, a notion
      confirmed by the inability of c-Myc to sensitize to RIP killing in cells lacking
      the obligate mitochondrial apoptotic effectors Bax and Bak. We conclude that the
      lethality of the RIP-activated cytosolic caspase 8 pathway is augmented by c-Myc
      priming mitochondria to release cytochrome c. This places the intersection of
      apoptotic synergy between c-Myc and death receptor signaling downstream of the
      death receptors.

PMID- 12202490
TI  - Solution structure of the phosphoryl transfer complex between the cytoplasmic A
      domain of the mannitol transporter IIMannitol and HPr of the Escherichia coli
      phosphotransferase system.
AB  - The solution structure of the complex between the cytoplasmic A domain (IIA(Mtl))
      of the mannitol transporter II(Mannitol) and the histidine-containing
      phosphocarrier protein (HPr) of the Escherichia coli phosphotransferase system
      has been solved by NMR, including the use of conjoined rigid body/torsion angle
      dynamics, and residual dipolar couplings, coupled with cross-validation, to
      permit accurate orientation of the two proteins. A convex surface on HPr, formed
      by helices 1 and 2, interacts with a complementary concave depression on the
      surface of IIA(Mtl) formed by helix 3, portions of helices 2 and 4, and beta
      strands 2 and 3. The majority of intermolecular contacts are hydrophobic, with a
      small number of electrostatic interactions at the periphery of the interface. The
      active site histidines, His-15 of HPr and His-65 of IIA(Mtl), are in close
      spatial proximity, and a pentacoordinate phosphoryl transition state can be
      readily accommodated with no change in protein-protein orientation and only
      minimal perturbations of the backbone immediately adjacent to the histidines.
      Comparison with two previously solved structures of complexes of HPr with partner
      proteins of the phosphotransferase system, the N-terminal domain of enzyme I
      (EIN) and enzyme IIA(Glucose) (IIA(Glc)), reveals a number of common features
      despite the fact that EIN, IIA(Glc), and IIA(Mtl) bear no structural resemblance
      to one another. Thus, entirely different underlying structural elements can form
      binding surfaces for HPr that are similar in terms of both shape and residue
      composition. These structural comparisons illustrate the roles of surface and
      residue complementarity, redundancy, incremental build-up of specificity and
      conformational side chain plasticity in the formation of transient specific
      protein-protein complexes in signal transduction pathways.

PMID- 12202491
TI  - Ionizing radiation activates nuclear protein phosphatase-1 by ATM-dependent
      dephosphorylation.
AB  - Ionizing radiation (IR) is known to activate multiple signaling pathways,
      resulting in diverse stress responses including apoptosis, cell cycle arrest, and
      gene induction. IR-activated cell cycle checkpoints are regulated by Ser/Thr
      phosphorylation, so we tested to see if protein phosphatases were targets of an
      IR-activated damage-sensing pathway. Jurkat cells were subjected to IR or sham
      radiation followed by brief (32)P metabolic labeling. Nuclear extracts were
      subjected to microcystin affinity chromatography to recover phosphatases, and the
      proteins were analyzed by two-dimensional gel electrophoresis. Protein sequencing
      revealed that the microcystin-bound proteins with the greatest reduction in (32)P
      intensity following IR were the alpha and delta isoforms of protein phosphatase 1
      (PP1). Both of these PP1 isoforms contain an Arg-Pro-Ile/Val-Thr-Pro-Pro-Arg
      sequence near the C terminus, a known site of phosphorylation by Cdc/Cdk kinases,
      and phosphorylation attenuates phosphatase activity. In wild-type Jurkat cells or
      ataxia telangiectasia (AT) cells that are stably transfected with full-length ATM
      kinase, IR resulted in net dephosphorylation of this site in PP1 and produced
      activation of PP1. However, in AT cells that are deficient in ATM, IR failed to
      induce dephosphorylation or activation of PP1. IR-induced PP1 activation in the
      nucleus may be a critical component in an ATM-mediated pathway controlling
      checkpoint activation.

PMID- 12202492
TI  - ABCA1 and scavenger receptor class B, type I, are modulators of reverse sterol
      transport at an in vitro blood-brain barrier constituted of porcine brain
      capillary endothelial cells.
AB  - The objective of the present study was to investigate the involvement of key
      players in reverse cholesterol/24(S)OH-cholesterol transport in primary porcine
      brain capillary endothelial cells (pBCEC) that constitute the BBB. We identified
      that, in addition to scavenger receptor class B, type I (SR-BI), pBCEC express
      ABCA1 and apolipoprotein A-I (apoA-I) mRNA and protein. Studies on the regulation
      of ABCA1 by the liver X receptor agonist 24(S)OH-cholesterol revealed increased
      ABCA1 expression and apoA-I-dependent [3H]cholesterol efflux from pBCEC. In
      unpolarized pBCEC, high density lipoprotein, subclass 3 (HDL3)-dependent
      [3H]cholesterol efflux, was unaffected by 24(S)OH-cholesterol treatment but was
      enhanced 5-fold in SR-BI overexpressing pBCEC. Efflux of cellular 24(S)-[3H]OH
      cholesterol was highly efficient, independent of ABCA1, and correlated with SR-BI
      expression. Polarized pBCEC were cultured on porous membrane filters that allow
      separate access to the apical and the basolateral compartment. Addition of
      cholesterol acceptors to the apical compartment resulted in preferential
      [3H]cholesterol efflux to the basolateral compartment. HDL3 was a better promoter
      of basolateral [3H]cholesterol efflux than lipid-free apoA-I. Basolateral
      pretreatment with 24(S)OH-cholesterol enhanced apoA-I-dependent basolateral
      cholesterol efflux up to 2-fold along with the induction of ABCA1 at the
      basolateral membrane. Secretion of apoA-I also occurred preferentially to the
      basolateral compartment, where the majority of apoA-I was recovered in an HDL
      like density range. In contrast, 24(S)-[3H]OH-cholesterol was mobilized
      efficiently to the apical compartment of the in vitro BBB by HDL3, low density
      lipoprotein, and serum. These results suggest the existence of an autoregulatory
      mechanism for removal of potentially neurotoxic 24(S)OH-cholesterol. In
      conclusion, the apoA-I/ABCA1- and HDL/SR-BI-dependent pathways modulate polarized
      sterol mobilization at the BBB.

PMID- 12202493
TI  - Nuclear translocation of insulin receptor substrate-1 by oncogenes and Igf-I.
      Effect on ribosomal RNA synthesis.
AB  - The insulin receptor substrate-1 (IRS-1) is one of the major substrates of both
      the insulin and IGF-I receptors and is generally localized in the
      cytosol/membrane fraction of the cell. We show here that a substantial fraction
      of IRS-1 is translocated to the nucleus in mouse embryo fibroblasts (MEF)
      expressing the simian virus 40 T antigen. Nuclear translocation of IRS-1 occurs
      also in MEF stimulated with IGF-I or in MEF expressing the oncogene v-src.
      Nuclear translocation of IRS-1 can be demonstrated by confocal microscopy,
      immunohistochemistry, or subcellular fractionation. An antibody to IRS-1
      immunoprecipitates from nuclear fractions (but not from cytosolic fractions) the
      upstream binding factor, which is a key regulator of RNA polymerase I activity
      and ribosomal RNA (rRNA) synthesis. In agreement with this finding, in 32D murine
      hemopoietic cells, nuclear translocation of IRS-1 correlates with a markedly
      increased rRNA synthesis. Our experiments suggest that nuclear IRS-1 may play a
      specialized role in rRNA synthesis and/or processing.

PMID- 12202494
TI  - Electrostatic effects and binding determinants in the catalysis of prolyl
      oligopeptidase. Site specific mutagenesis at the oxyanion binding site.
AB  - Prolyl oligopeptidase, a member of a new family of serine peptidases, plays an
      important role in memory disorders. Earlier x-ray crystallographic investigations
      indicated that stabilization of the tetrahedral transition state of the reaction
      involved hydrogen bond formation between the oxyanion of the tetrahedral
      intermediate and the OH group of Tyr(473). The contribution of the OH group was
      tested with the Y473F variant using various substrates. The charged succinyl-Gly
      Pro-4-nitroanilide was hydrolyzed with a much lower k(cat)/K(m) compared with the
      neutral benzyloxycarbonyl-G1y-Pro-2-naphthylamide, although the binding modes of
      the two substrates were similar, as shown by x-ray crystallography. This
      suggested that electrostatic interactions between Arg(643) and the succinyl group
      competed with the productive binding mechanism. Unlike most enzyme reactions,
      catalysis by the wild-type enzyme exhibited positive activation entropy. In
      contrast, the activation entropy for the Y473F variant was negative, suggesting
      that the tyrosine OH group is involved in stabilizing both the transition state
      and the water shell at the active site. Importantly, Tyr(473) is also implicated
      in the formation of the enzyme-substrate complex. The nonlinear Arrhenius plot
      suggested a greater significance of the oxyanion binding site at physiological
      temperature. The results indicated that Tyr(473) was more needed at high pH, at
      high temperature, and with charged substrates exhibiting "internally competitive
      inhibition."

PMID- 12202495
TI  - Identification of ribosomal proteins specific to higher eukaryotic organisms.
AB  - This report describes the identification of a novel protein named PS1D (Genbank
      accession number ), which is composed of an S1-like RNA-binding domain, a
      (cysteine)x3-(histidine) CCCH-zinc finger, and a very basic carboxyl domain. PS1D
      is expressed as two isoforms, probably resulting from the alternative splicing of
      mRNA. The long PS1D isoform differs from the short one by the presence of 48
      additional amino acids at its amino-terminal extremity. Analysis of PS1D
      subcellular distribution by cell fractionation reveals that this protein belongs
      to the core of the eukaryotic 60S ribosomal subunit. Interestingly, PS1D protein
      is a highly conserved protein among mammalians as murine, human, and simian PS1D
      homologues share more than 95% identity. In contrast, no homologous protein is
      found in lower eukaryotes such as yeast and Caenorhabditis elegans. These
      observations indicate that PS1D is the first eukaryotic ribosomal protein that is
      specific to higher eukaryotes.

PMID- 12202496
TI  - Retinal pigment epithelial cell distribution in central retina of rhesus monkeys.
AB  - PURPOSE: To determine the cell density profile of the retinal pigment epithelium
      (RPE) in the central retina and relate it to the distribution of photoreceptors.
      METHODS: Wholemounts of rhesus monkey (Macaca mulatta) retinas with the choroid
      removed but the RPE attached were stained with the nuclear stain 4',6-diamidine-2
      phenylindole dihydrochloride (DAPI) and imaged with a fluorescence microscope.
      RPE cell nuclei were counted at the foveal center and at 0.4-mm intervals along
      the vertical meridian. The number of photoreceptors per RPE cell at each location
      was estimated by using previously published data on the distribution of rhesus
      photoreceptors. RESULTS: Data were collected from eight retinas. Mean RPE cell
      density increased from a relatively stable baseline of approximately 4000 RPE
      cells/mm(2) beyond 2 mm (10 degrees ) eccentricity to more than 7000 cells/mm(2)
      at the center of the fovea. The number of cones per RPE cell in the rhesus retina
      was approximately 20:1 in the foveal center (similar to the human retina) and
      only approximately 1.5:1 in the parafovea. However, when the rods were included,
      and the total number of photoreceptors per RPE cell were considered, the ratio of
      photoreceptors to RPE cells was lower in the fovea than in the remainder of the
      central retina. CONCLUSIONS: In spite of the high cone density, there is a
      relatively low number of photoreceptors per RPE cell in the fovea. This may limit
      the metabolic demands on foveal RPE cells and help to preserve their functions in
      the face of aging and disease.

PMID- 12202497
TI  - ABCA4 gene mutations in Japanese patients with Stargardt disease and retinitis
      pigmentosa.
AB  - PURPOSE: To evaluate photoreceptor cell-specific adenosine triphosphate (ATP)
      binding cassette transporter (ABCA4) gene mutations in Japanese patients with
      Stargardt disease (STGD) and the correlation of these mutations to clinical
      phenotypes. METHODS: Serum was obtained from 10 unrelated Japanese patients with
      STGD and 96 unrelated Japanese patients with autosomal recessive retinitis
      pigmentosa (arRP). All 50 ABCA4 gene exons of the patients with STGD were
      screened for mutations by a combination of single-strand conformation
      polymorphism analysis and polymerase chain reaction (PCR) direct-sequencing
      techniques. By restriction enzyme digestion, primer extension analysis, and PCR
      direct sequencing techniques, the patients with arRP were screened for three
      segregated, presumably null ABCA4 gene mutations observed in Japanese patients
      with STGD. RESULTS: Three novel, presumably null mutations of the ABCA4 gene,
      IVS7-45_952delinsTCTGACC, IVS12+2T-->G, and 1894delA, were identified. The
      Arg2149stop mutation that had been found in a white patient with STGD in a prior
      study was also found in a Japanese patient. Two arRP-affected siblings and two
      unrelated patients with STGD were found to be homozygous for the same IVS12+2T-
      >G mutation, and three other arRP-affected siblings were carriers of the IVS12+2T
      ->G mutation and/or the IVS7-45_952delinsTCTGACC mutation. These three siblings
      with arRP showed only atrophic degeneration in the macula early after the onset
      of the disease, and STGD had been diagnosed. CONCLUSIONS: Three novel ABCA4 gene
      mutations were identified in Japanese patients with STGD and arRP. Mutations in
      the ABCA4 gene can cause panretinal degeneration that changes its clinical
      appearance from STGD to arRP over time.

PMID- 12202498
TI  - Global gene expression analysis in a mouse model for Norrie disease: late
      involvement of photoreceptor cells.
AB  - PURPOSE: Mutations in the NDP gene give rise to a variety of eye diseases,
      including classic Norrie disease (ND), X-linked exudative vitreoretinopathy
      (EVRX), retinal telangiectasis (Coats disease), and advanced retinopathy of
      prematurity (ROP). The gene product is a cystine-knot-containing extracellular
      signaling molecule of unknown function. In the current study, gene expression was
      determined in a mouse model of ND, to unravel disease-associated mechanisms at
      the molecular level. METHODS: Gene transcription in the eyes of 2-year-old Ndp
      knockout mice was compared with that in the eyes of age-matched wild-type control
      animals, by means of cDNA subtraction and microarrays. Clones (n = 3072) from the
      cDNA subtraction libraries were spotted onto glass slides and hybridized with
      fluorescently labeled RNA-derived targets. More than 230 differentially expressed
      clones were sequenced, and their expression patterns were verified by virtual
      Northern blot analysis. RESULTS: Numerous gene transcripts that are absent or
      downregulated in the eye of Ndp knockout mice are photoreceptor cell specific. In
      younger Ndp knockout mice (up to 1 year old), however, all these transcripts were
      found to be expressed at normal levels. CONCLUSIONS: The identification of
      numerous photoreceptor cell-specific transcripts with a reduced expression in 2
      year-old, but not in young, Ndp knockout mice indicates that normal gene
      expression in these light-sensitive cells of mutant mice is established and
      maintained over a long period and that rods and cones are affected relatively
      late in the mouse model of ND. Obviously, the absence of the Ndp gene product is
      not compatible with long-term survival of photoreceptor cells in the mouse.

PMID- 12202499
TI  - NF-kappaB activation in light-induced retinal degeneration in a mouse model.
AB  - PURPOSE: To investigate the modulation of nuclear factor (NF)-kappaB in light
      induced photoreceptor degeneration in a mouse model. METHODS: Mice were exposed
      to intense green light. Light-induced activation of NF-kappaB and its nuclear
      localization were studied by immunohistochemistry. The NF-kappaB DNA-binding
      activity in the retinas after exposure to light was measured by electrophoretic
      mobility shift assay (EMSA). Nuclear transactivation of NF-kappaB in the
      photoreceptor cells was determined by quantitative real-time (qRT)-PCR. The
      amount of NF-kappaB p65 in the photoreceptor cells after exposure to light was
      assessed by Western blot analysis. To obtain more photoreceptor-specific
      information, microdissected photoreceptor cells were used in some studies.
      RESULTS: By an immunohistochemical method, the perinuclear region of the
      photoreceptor cells was heavily labeled with an antibody to activated NF-kappaB
      after a 1-hour exposure to light. Nuclear localization of NF-kappaB in the
      photoreceptor nucleus was seen at 12 hours. In the experiments involving 3 hours
      of exposure to light followed by recovery in the dark, nuclear localization of NF
      kappaB was also noted after 12 hours' recovery in the dark. During continuous
      exposure to light, the NF-kappaB DNA-binding activity gradually increased and
      reached its maximum at 12 hours. There was an increase of NF-kappaB p65 protein
      at 3 hours. The mRNA levels of IkappaBalpha were upregulated after 6 hours'
      exposure to light. CONCLUSIONS: Intense light activated NF-kappaB in the
      photoreceptor cells in vivo, increased the NF-kappaB DNA-binding activity, and
      increased the expression of mRNA of IkappaBalpha, a target gene of NF-kappaB.

PMID- 12202500
TI  - Identification of estrogen and progesterone receptor mRNA expression in the
      conjunctiva of premenopausal women.
AB  - PURPOSE: The purpose of the present study was to identify the expression of
      estrogen and progesterone receptor mRNA and of estrogen and progesterone receptor
      protein in the conjunctiva of healthy women. METHODS: Specimens of conjunctival
      tissue of 10 premenopausal women (age range, 13-38 years) were obtained during
      ophthalmic surgery in patients under general anesthesia. Specimens of
      approximately 4 mm(2) were taken from superior, nasal, or temporal bulbar
      conjunctiva adjacent to the bulbus and were immediately deep frozen with liquid
      nitrogen. Four women underwent strabismus surgery, two had phacoemulsification,
      and four had vitrectomy. Only three women were taking oral contraceptives. The
      expression of estrogen receptor (ER)-alpha, ERbeta, and progesterone receptor
      (PR) mRNA was analyzed by RT-PCR. Western blot analysis on nuclear extracts was
      performed with the anti-ERalpha mouse monoclonal antibody AB-15, the anti-ERbeta
      mouse monoclonal antibody 6B12, and the anti-PR mouse monoclonal antibody PgR
      636. RESULTS: In two samples, ERalpha, ERbeta, and PR mRNAs were not accessible
      because of highly degraded RNA. In the remaining eight samples, an appearance
      rate of 100% was obtained for all three mRNAs. Similarly, an appearance rate of
      100% was obtained for ERalpha, ERbeta, and PR protein in nine tissue samples
      accessible for analysis; one sample could not be analyzed due to a low amount of
      tissue. CONCLUSIONS: This study confirms the existence of estrogen and
      progesterone receptors in the human conjunctiva of premenopausal females. Because
      the proteins of estrogen and progesterone were also found in this study's
      specimens, the data indicate that the conjunctiva is a target site for sex
      steroids. Future studies are needed to elucidate the role of these receptors in
      ocular diseases involving the conjunctiva.

PMID- 12202501
TI  - Mutational analysis of selected genes in the TGFbeta, Wnt, pRb, and p53 pathways
      in primary uveal melanoma.
AB  - PURPOSE: It is known that the pRb pathway cell-cycle inhibitor p16(INK4A) plays a
      significant role in cutaneous melanoma and that alteration of p16(INK4A), which
      resides within the 9p21-22 locus that also contains p15(INK4B) and p14(ARF), may
      occur in up to one third of uveal melanomas. The absence of TGFbeta
      responsiveness noted in cultured uveal melanoma cells also suggests that the
      TGFbeta pathway plays a role in the formation of this tumor. Therefore,
      mutational screening was performed in several key genes in tumor-suppressor
      pathways that are known to be altered in some uveal melanomas. METHODS: Using
      denaturing high-performance liquid chromatography (DHPLC) analysis and DNA
      sequencing, a series of 67 uveal melanomas were screened for inactivating
      mutations in the TGFbeta pathway members Smad4 and TGFbeta receptor type 2
      (TGFbetaR2), the downstream cell-cycle inhibitor p15(INK4B), and the cell-cycle
      inhibitors p14(ARF) and p16(INK4A). p16(INK4A) was also investigated for promoter
      hypermethylation. Mutational analysis was also performed on the Wnt pathway gene
      beta-catenin, known to be mutated in approximately one quarter of cutaneous
      melanoma cell lines. RESULTS: Polymorphisms in p16(INK4A) were detected in 3 of
      50 samples, but no inactivating mutations were detected in any of the genes
      screened. Promoter hypermethylation of p16(INK4A) was detected in 5 of 55 tumors,
      and loss of heterozygosity of the p16(INK4A) locus was detected in 5 of 16
      tumors. CONCLUSIONS: Most primary uveal melanomas do not appear to contain
      somatic mutations in Smad4, TGFbetaR2, p14(ARF), p15(INK4B), p16(INK4A), or beta
      catenin. However, methylation of the p16(INK4A) promoter and loss of
      heterozygosity of the p14(ARF)-p16(INK4A) locus occurs in some tumors.

PMID- 12202502
TI  - The Hong Kong progressive lens myopia control study: study design and main
      findings.
AB  - PURPOSE: To determine whether the use of progressive addition spectacle lenses
      reduced the progression of myopia, over a 2-year period, in Hong Kong children
      between the ages of 7 and 10.5 years. METHODS: A clinical trial was carried out
      to compare the progression in myopia in a treatment group of 138 (121 retained)
      subjects wearing progressive lenses (PAL; add +1.50 D) and in a control group of
      160 (133 retained) subjects wearing single vision lenses (SV). The research
      design was masked with random allocation to groups. Primary measurements outcomes
      were spherical equivalent refractive error and axial length (both measured using
      a cycloplegic agent). RESULTS: There were no statistically significant
      differences between the PAL and the SV groups for of any of the baseline outcome
      measures. After 2 years there had been statistically significant increases in
      myopia and axial length in both groups; however, there was no difference in the
      increases that occurred between the two groups. CONCLUSIONS: The research design
      used resulted in matched treatment and control groups. There was no evidence that
      progression of myopia was retarded by wearing progressive addition lenses, either
      in terms of refractive error or axial length.

PMID- 12202503
TI  - Measuring low-vision rehabilitation outcomes with the NEI VFQ-25.
AB  - PURPOSE: To evaluate the sensitivity of the National Eye Institute Visual
      Functioning Questionnaire-25 (NEI VFQ-25) to change in visual abilities after low
      vision rehabilitation in two different Veterans Administration (VA) low-vision
      programs METHODS: Seventy-seven legally blind veterans from the Blind
      Rehabilitation Center (BRC) at Hines VA Hospital and 51 partially sighted
      veterans from the Visual Impairment Center to Optimize Remaining Sight (VICTORS)
      program at the Chicago Health Care Network, West Side Division, were administered
      the NEI VFQ-25 plus supplement in interview format at admission and discharge.
      Instructions for administration were modified to have study participants answer
      all the questions as if they were wearing glasses or contact lenses or were using
      low-vision devices. Interval measures of person ability and item difficulty were
      estimated from the patients' responses to 34 of the 39 items on the VFQ-25 plus
      supplement before and after rehabilitation, by the polytomous rating scale
      measurement model of Wright and Masters. RESULTS: In VICTORS patients, item order
      by difficulty before rehabilitation agreed with item order for BRC patients.
      Visual ability scales are used similarly by different patients with different
      degrees of low vision. Based on prerehabilitation person measure distributions,
      VICTORS patients were less disabled, as would be predicted by visual acuity, than
      were BRC patients. After rehabilitation, estimated item difficulty for 4 of the
      34 items decreased significantly in both BRC and VICTORS patients. CONCLUSIONS:
      The present study demonstrates that the NEI VFQ-25 plus supplement can be used to
      measure the effects of low-vision rehabilitation; however, only 7 of the 34 items
      tested are sensitive to change after rehabilitation. Targeted activities, such as
      reading ordinary print, small print, and street signs are easier to perform for
      graduates of both programs after rehabilitation. The patients' visual ability
      also shows improvement in both BRC and VICTORS. Improvement in visual ability is
      independent of change in difficulty of targeted items. Although this was not a
      controlled clinical trial, the decrease in difficulty of targeted items may
      reflect the use of low-vision aids and training to make tasks easier. The change
      in visual ability may reflect positive outcomes of rehabilitation or may be the
      consequence of patients' overestimates of their functional ability at the time of
      discharge.

PMID- 12202504
TI  - Refractive errors and 10-year incidence of age-related maculopathy.
AB  - PURPOSE: To describe the relationship of refractive errors to the 10-year
      incidence of age-related maculopathy (ARM) in a defined white population.
      METHODS: Persons aged 43 to 86 years of age in Beaver Dam, Wisconsin, were
      invited for a baseline examination from 1988 through 1990, and follow-up
      examinations 5 and 10 years later (n = 3684). Refraction was measured at
      baseline, with myopia defined as a spherical equivalent of -1.00 D or less,
      emmetropia as -0.75 to +0.75 D and hyperopia as +1.00 D or more. At each
      examination, signs of ARM were ascertained from grading stereoscopic color fundus
      photographs based on a standard protocol. The association between baseline
      refractive status and the 10-year incidence and progression of ARM was analyzed.
      RESULTS: The 10-year cumulative incidence for early ARM was 7.1%, 7.7%, and
      11.7%, in eyes with myopia, emmetropia, and hyperopia, respectively. The
      corresponding 10-year cumulative incidence for late ARM was 0.3%, 0.8%, and 2.2%.
      When age was controlled for, there was no association between myopia and incident
      early (relative risk [RR] 1.0, 95% confidence interval [CI], 0.7-1.3) and late
      (RR 0.5, 95% CI, 0.2-1.5) ARM. Similarly, after controlling for age, hyperopia
      was not associated with incident early (RR 0.9, 95% CI, 0.7-1.1) or late (RR 1.2,
      95% CI, 0.6-2.3) ARM. CONCLUSIONS: These prospective population-based data
      provide no evidence of an association between refractive errors and risk of ARM.

PMID- 12202505
TI  - A self-assessment instrument designed for measuring independent mobility in RP
      patients: generalizability to glaucoma patients.
AB  - PURPOSE: To determine whether the patient-based assessment of difficulty in
      mobility, developed and validated in a group of patients with retinitis
      pigmentosa (RP), is valid for measuring perceived visual ability for independent
      mobility in patients with glaucoma. METHODS: A mobility questionnaire that had
      previously been developed was administered to 83 patient-volunteers who had
      various amounts of visual impairment caused by glaucoma. Each volunteer rated the
      perceived difficulty of walking independently in each of 35 mobility situations.
      A Rasch analysis of the ordinal difficulty ratings was used to estimate interval
      measures of perceived visual ability for independent mobility. RESULTS: The
      instrument showed good construct and content validity and high reliability
      scores. Criterion validity of the instrument was demonstrated by its ability to
      discriminate mobility-related behaviors such as fear of falling, asking for
      accompaniment, and believing their ability to travel independently is less than
      that of persons with normal vision. To make the perceived mobility scale
      comparable for the two diagnostic groups the questionnaire was restricted to
      those items whose difference in item-logit distributions was within +/-3 (18
      items). Using the same instrument calibration, we compared the person measures
      between the patients with glaucoma and those with RP. Patients with glaucoma had,
      on average, higher perceived visual ability for independent mobility than those
      with RP. CONCLUSIONS: The instrument developed for patients with RP, to determine
      difficulty across a range of mobility situations, is a valid measure of perceived
      ability for independent mobility in patients with glaucoma.

PMID- 12202506
TI  - Apparent accommodation and corneal wavefront aberration in pseudophakic eyes.
AB  - PURPOSE: To assess the relationship between apparent accommodation in
      pseudophakic eyes, multifocal corneal effects, and wavefront aberrations of the
      cornea. METHODS: In 102 eyes of 86 patients who had undergone phacoemulsification
      and posterior chamber intraocular lens implantation, the amount of apparent
      accommodation was measured with an accommodometer. The degree of corneal
      multifocality was determined on the corneal topography by measuring the maximum
      and minimum corneal refractive powers within the pupillary area. Wavefront
      aberrations of the cornea were calculated by expanding the height data of the
      corneal topography into Zernike polynomials for individual pupil size. The
      influence of higher-order aberration on the retinal image quality was simulated
      by computing the point-spread function (PSF) and modulation-transfer function
      (MTF) from the aberration function. RESULTS: There was a significant positive
      correlation between the amount of apparent accommodation and corneal
      multifocality (Pearson correlation coefficient, r = 0.451, P < 0.001). The coma
      like aberration showed a significant positive correlation with the amount of
      apparent accommodation (r = 0.440, P < 0.001), but the spherical-like aberration
      did not (r = 0.001, P = 0.993). Among the coma-like aberrations, the component
      representing vertically asymmetrical distribution of corneal refractive power
      with greater refraction located in the lower part of the eye was most relevant to
      apparent accommodation. Computer simulation of PSF and MTF indicated that a focus
      shift of 0.5 D deteriorated the retinal image significantly more in eyes without
      higher-order aberrations than in eyes with a moderate amount of coma-like
      aberrations. CONCLUSIONS: Coma-like aberration of the cornea, along with corneal
      multifocality, contributes to apparent accommodation in pseudophakic eyes.

PMID- 12202507
TI  - Ciliary neurotrophic factor released by corneal endothelium surviving oxidative
      stress ex vivo.
AB  - PURPOSE: To demonstrate that corneal endothelial (CE) cells that survive
      oxidative stress in corneas release ciliary neurotrophic factor (CNTF), which
      does not possess the secretion signal sequence. METHODS: CNTF and CNTF receptor
      alpha subunit (CNTFRalpha) in CE cells and cell-conditioned medium (H2O2 and PBS
      placed in bovine corneal cups for 30 minutes at 37 degrees C) in explant cultures
      were demonstrated by Western blot (WB) and immunoprecipitation (IP). The number
      of dead CE cells was determined microscopically with a viability kit, by an
      observer uninformed of the explants' identities. CNTF and CNTFRalpha synthesis
      and release by CE cells in 35S-methionine-labeled (0.1 mCi/mL for 8 hours at 37
      degrees C) corneal cups were shown by autoradiography and WB. RESULTS. CE cells
      in fresh bovine eyes expressed a 25-kDa CNTF that was recognized by three
      different antibodies. CE cells expressed a 61-kDa CNTF-immunoreactive molecule
      (IM), which disappeared from the CE cells in H2O2-conditioned corneal cups,
      concomitant with the appearance of the 25-kDa CNTF in the conditioned medium.
      Corneal cups containing 0, 0.006, 0.012, 0.023, 0.045, 0.09, 0.18, and 0.35 mM
      H2O2 demonstrated relative levels of CE cell 61-kDa CNTF-IM of 100%, 84%, 77%,
      61%, 52%, 39%, 35%, and 35%, respectively, whereas levels of 25-kDa CNTF in the
      conditioned medium were 23%, 32%, 39%, 63%, 80%, 90%, 100%, and 63%,
      respectively. CE cells expressed a 53-kDa CNTFRalpha that, along with trace
      amounts of a 61-kDa CNTFRalpha-IM, appeared concomitantly with the 25-kDa CNTF in
      the conditioned medium. H2O2 (0-0.56 mM) did not affect the viability of CE cells
      (15 dead cells per 600 cells). CE cells in 35S-methionine-labeled corneal cups
      synthesized and released a 35S 61-kDa molecule that was both CNTF- and CNTFRalpha
      immunoreactive in an H2O2-dependent manner, whereas 25-kDa CNTF was detected in
      the (35)S-methionine labeling medium. CONCLUSIONS: CE cells release autocrine
      CNTF under sublethal oxidative stress by a mechanism that involves CNTFRalpha and
      the formation of a 61-kDa CNTF/CNTFRalpha-IM.

PMID- 12202508
TI  - Detection of differentially expressed genes in healing mouse corneas, using cDNA
      microarrays.
AB  - PURPOSE: To identify differentially expressed genes in healing mouse corneas by
      using cDNA microarrays. METHODS: Transepithelial excimer laser ablations were
      performed on mouse corneas, and the wounds were allowed to heal partially in vivo
      for 18 to 22 hours. Total RNA was isolated from both normal and healing corneas
      and was used for synthesis of cDNA probes. 33P-labeled exponential cDNA probes
      were hybridized to mouse cDNA nylon arrays. RESULTS: Of the 1176 genes on the
      nylon arrays, the expression of 37 was upregulated and that of 27 was
      downregulated more than fivefold in the healing corneas compared with the normal,
      uninjured corneas. Interleukin (IL)-1beta, laminin-5, and thrombospondin-1, which
      have been shown to be upregulated in healing corneas, were all found to be
      induced in the corneas in response to excimer laser treatment. Many genes were
      identified for the first time to be differentially regulated during corneal wound
      healing. Among the upregulated genes were intercellular adhesion molecule (ICAM)
      1, macrophage inflammatory proteins, suppressors of cytokine signaling proteins
      (SOCS), IL-10 receptor, and galectin-7. Among the downregulated genes were
      connexin-31, a gap junction protein; ZO1 and occludin, tight junction proteins;
      and Smad2, a key component in the TGFbeta signaling pathway. Microarray data were
      validated on a limited number of genes by semiquantitative RT-PCR and Western
      blot analyses. CONCLUSIONS: Gene array technology was used to identify for the
      first time many genes that are differentially regulated during corneal wound
      healing. These differentially expressed genes have not previously been
      investigated in the context of wound healing and represent novel factors for
      further study of the mechanism of wound healing.

PMID- 12202509
TI  - The inflammatory milieu associated with conjunctivalized cornea and its
      alteration with IL-1 RA gene therapy.
AB  - PURPOSE: This study was designed to gain an insight into the inflammatory milieu
      into which a donor limbal graft is routinely introduced. The objective of this
      study was to modulate this environment by gene therapy with the anti-inflammatory
      cytokine interleukin-1 receptor antagonist (IL-1 RA). METHODS: In a mouse model,
      the ocular surface cytokine environment associated with a conjunctivalized cornea
      was assessed 4 weeks after injury. Total corneal epithelial and limbal
      debridement was performed with a combination of alkali and scrape injury. The
      cytokines and adhesion molecules measured included IL-1alpha, IL-1beta, IL-6,
      VEGF, intercellular adhesion molecule (ICAM)-1, and vascular adhesion molecule
      (VCAM)-1, by real-time PCR or ELISA. Injured corneas were transfected with IL-1
      RA by injection of naked plasmid vector pIRES-EGFP-IL-1 RA immediately after
      injury. Corneas transfected with pIRES-EGFP served as the control. Expression of
      corneal IL-1 RA after transfection with pIRES-EGFP-IL1-RA was assessed over a 2
      week period by real-time PCR and Western blot analysis. In addition, limbal stem
      cell grafts transfected with IL-1 RA were assessed for leukocyte influx. RESULTS:
      Conjunctivalized corneas showed increased expression of IL-1alpha, IL-1beta, IL-1
      RA, IL-6, VEGF, ICAM-1, and VCAM-1, compared with normal cornea. Transfection
      efficiency experiments indicated that corneal expression of IL-1 RA peaked
      between 12 and 24 hours and lasted up to 2 weeks after the initial transfection.
      IL-1 RA corneal gene therapy resulted in a downregulation of IL-1beta and VCAM-1
      expression at 4 weeks after injury, whereas downregulation of IL-6 was evident
      only at 1 week after injury. Corneal neovascularization was also reduced. In
      addition, corneal limbal stem cell grafts transfected with IL-1 RA showed a
      decreased leukocyte influx compared with control grafts. CONCLUSIONS:
      Transfection of a cornea with IL-1 RA immediately after epithelial injury
      selectively altered the cytokine profile of the resultant conjunctivalized cornea
      and suppressed corneal neovascularization. Transfection of corneal limbal donor
      tissue with IL-1 RA before engraftment can reduce leukocyte influx into the
      graft. The findings demonstrate the feasibility of using transient cytokine gene
      expression, either in donor or recipient corneal tissue, to alter the ocular
      surface environment beneficially.

PMID- 12202510
TI  - Osmosensitive taurine transporter expression and activity in human corneal
      epithelial cells.
AB  - PURPOSE: To characterize in SV40-immortalized human corneal epithelial cells
      (tHCEC) osmosensitive taurine transporter gene and protein expression as well as
      its functional activity. To evaluate whether medium supplementation with taurine
      improves cell viability during a hypertonic challenge. METHODS: tHCEC were
      preincubated for up to 48 hours in hypertonic DMEM medium (i.e., up to 500
      mosmol/kg). Taurine uptake was monitored through measurements of intracellular
      [3H]taurine accumulation. Gene and protein expression was detected by Northern
      and Western blot analyses, respectively. An amino acid analyzer measured
      intracellular cold taurine content. The live/dead assay evaluated with confocal
      microscopy determined cell viability. RESULTS: Na+-dependent taurine uptake
      occurred in an isotonic (310 mosmol/kg) medium. The apparent Michaelis-Menten
      constant, K(t), for taurine was 4.6 micro M, and uptake increased as a function
      of exposure time and rises in osmolality. Exposure for 12 hours to a 450
      mosmol/kg medium increased uptake by 4.1-fold. However, after 48 hours of
      exposure to this medium, taurine uptake returned to its isotonic level. With
      time, biphasic changes occurred in taurine transporter gene and protein
      expression and taurine transport activity as well as elevating intracellular
      taurine content by 4.5-fold. Taurine medium supplementation for 48 hours improved
      cell viability. CONCLUSIONS: tHCEC express Na+-dependent osmosensitive taurine
      transport activity. The hypertonic-induced biphasic effects on gene and protein
      expression as well as transport activity suggest feedback regulation of these
      responses. Rises in intracellular taurine do not appear to be essential for
      osmoregulation, but instead enhance cell survival perhaps through a membrane
      stabilizer or an antioxidant effect.

PMID- 12202511
TI  - Quantitative analysis of the structure of the human extraocular muscle pulley
      system.
AB  - PURPOSE: Extraocular muscle (EOM) paths are constrained by connective tissue
      pulleys serving as functional origins. The quantitative structural features of
      pulleys and their intercouplings and orbital suspensions remain undetermined.
      This study was designed to quantify the composition of EOM pulleys and suspensory
      tissues. METHODS: Five human orbits, ages 33 weeks gestation to 93 years, were
      imaged intact by magnetic resonance (MRI), serially sectioned at 10 micro m
      thickness, and stained for collagen, elastin, and smooth muscle (SM). With MRI
      used as a reference, digital images of sections were geometrically corrected for
      shrinkage and processing deformations, and normalized to standard normal adult
      globe diameter. EOM pulleys, interconnections, suspensory tissues, and entheses
      were quantitatively analyzed for collagen, elastin, and SM thickness and density.
      RESULTS: Rectus and inferior oblique pulleys had uniform structural features in
      all specimens, comprising a dense EOM encirclement by collagen 1 to 2 mm thick.
      Elastin distribution varied, but was greatest in the orbital suspension of the
      medial rectus pulley and in a band from it to the inferior rectus pulley. This
      region corresponded to maximum SM density. Structural features of pulleys,
      intercouplings, and entheses were similar among specimens. The major mechanical
      couplings to the osseous orbit were near the medial and lateral rectus pulleys.
      CONCLUSIONS: Quantitative analysis of structure and composition of EOM pulleys
      and their suspensions is consistent with in vivo MRI observations showing
      discrete inflections in EOM paths that shift predictably with gaze. Focal SM
      distributions in the suspensions suggest distinct roles in stiffening as well as
      shifting rectus pulleys.

PMID- 12202512
TI  - The effect of apomorphine on blink kinematics in subhuman primates with and
      without facial nerve palsy.
AB  - PURPOSE: The purpose of this study was to document the effect of acutely
      delivered apomorphine, a dopamine receptor agonist with both D1 and D2
      properties, on blink rate and the amplitude-velocity characteristics of eyelid
      kinematics in a group of nonhuman primates. METHODS: Three cynomolgus and two
      rhesus macaques underwent baseline recordings for eyelid kinematics, using the
      Robinson search coil technique. Next, each animal received a 0.15-mg/kg
      subcutaneous injection of apomorphine. Recordings were taken at 45 and 90
      minutes, respectively, after injection. Blink rates per minute were obtained, and
      main sequence relationships were calculated for every animal. The data were
      pooled for each eyelid, excluding one monkey who was affected by facial nerve
      palsy and was analyzed separately. RESULTS: Monkeys with normal facial
      musculature and normal baseline blink rates showed consistently longer, faster
      blinks after apomorphine. The main sequence relationship, although tending to be
      lower, was not statistically different from baseline. One monkey, with prior
      facial nerve palsy and a very steep amplitude versus peak velocity relationship,
      showed normalization of the main sequence slope after apomorphine at both 45 and
      90 minutes after injection. CONCLUSIONS: Apomorphine consistently lowers blink
      rate and changed blink metrics in normal monkeys and, more dramatically, in a
      monkey with facial nerve palsy. These findings add credence to models in which
      dopamine deficiency plays a role in the modulation of blink kinematics.

PMID- 12202513
TI  - The latency of saccades, vergence, and combined eye movements in children and in
      adults.
AB  - PURPOSE: To examine the latency of eye movements in three-dimensional space
      (saccade, vergence, and combined saccade-vergence) in children and adults.
      METHODS: Fifteen normal children (4.5-12 years of age) and 15 normal adults (22
      44 years of age) were tested. A standard paradigm was used to elicit pure lateral
      saccades at far and close viewing distance, pure vergence (convergence and
      divergence), and saccade combined with vergence movements. Horizontal eye
      movements from both eyes were recorded simultaneously by the oculometer, a
      photoelectric device. RESULTS: The mean latency in saccades, vergence, and
      combined eye movements was longer in children than in adults; the variability of
      such latency values was also larger in children. There was a progressive decrease
      with age in mean latency. All latencies approached or reached adult levels at
      approximately 10 to 12 years of age. Latency of saccades at close viewing
      distance was shorter than that at far in both adults and children. Convergence
      latency was longer than divergence latency in adults and most of the children.
      Latency of components of combined movements was longer than that of corresponding
      pure movements. Children initiated combined movements by triggering the vergence
      component first, whereas adults did not show a dominant pattern. The percentage
      of synchronous start of the two components was significantly higher in adults.
      CONCLUSIONS: Saccade- and vergence-triggering mechanisms are distinct and mature
      progressively and in parallel with age. The capacity for synchronization of the
      two components of combined eye movements develops more slowly and remains below
      adult level, even at the age of 12 years.

PMID- 12202514
TI  - The pore density in the inner wall endothelium of Schlemm's canal of glaucomatous
      eyes.
AB  - PURPOSE: In a prior study, it has been reported that glaucomatous eyes have a
      significantly lower density of pores in the inner wall of Schlemm's canal than do
      normal eyes. However, in that study the glaucomatous eyes were fixed at much
      lower flow rates than the normal eyes, and that is now known to affect inner wall
      pore density. The objective of the current study was to compare the inner wall's
      pore density in glaucomatous and normal eyes, accounting for the effects of
      fixation conditions. METHODS: Outflow facility was measured in enucleated
      glaucomatous human eyes. Eyes were fixed under constant flow conditions,
      microdissected to expose the inner wall of Schlemm's canal, and prepared for
      scanning electron microscopy (SEM). The density and diameter of the two
      subpopulations of pores in the inner wall, intracellular and intercellular (or
      "border") pores, were measured. Data were compared with those in previous studies
      of normal eyes. RESULTS: As previously reported, pore density decreased with
      increasing postmortem time and increased with increasing volume of fixative
      passed through the outflow pathway and with increasing fixation time. Linear
      regression analysis indicated that glaucomatous eyes had less than one fifth the
      number of pores than normal eyes have, after accounting for the influence of
      volume of fixative perfused through the eyes (835 pores/mm(2) in normal eyes
      versus 160 pores/mm(2) in glaucomatous eyes). A nonlinear regression of pore
      density versus fixative volume produced a pore density at zero fixative volume
      that was not statistically different from zero. If true, this implies that all
      (or nearly all) inner wall pores observed by SEM are fixation artifacts. The
      density of intracellular pores and the diameter of these pores correlated with
      the density and diameter of the border pores, respectively. CONCLUSIONS: Inner
      wall pores are reduced in glaucomatous eyes. If pores are physiological
      structures, the elevated intraocular pressure characteristic of glaucoma may be
      explained by decreased porosity of the inner wall endothelium. Both border and
      intracellular pores seem to be induced in a similar fashion by fixation. The
      unlikely possibility that all inner wall pores are fixation-induced cannot be
      excluded. If so, a fundamental reassessment of the mechanism by which aqueous
      humor crosses the inner wall endothelium is necessary.

PMID- 12202515
TI  - Morphologic predictive factors for development of optic disc hemorrhages in
      glaucoma.
AB  - PURPOSE: To evaluate which optic disc parameters are predictive factors for the
      development of disc hemorrhages in chronic open-angle glaucoma. METHODS: The
      prospective comparative clinical observational study included 432 eyes of 281
      white patients with chronic open-angle glaucoma. Mean follow-up time was 38.8
      months (median, 31.5). Eyes in the whole study group were divided into those with
      an optic disc hemorrhage during the follow-up period (hemorrhagic group; n = 38;
      8.8%), those without disc hemorrhages and with neuroretinal rim loss as sign of
      progression of glaucoma (rim loss group; n = 42; 9.7%), and those with neither
      disc hemorrhages nor neuroretinal rim loss (stable group; n = 352; 81.5%). Color
      stereo optic disc photographs were obtained repeatedly in all patients and
      subjected to qualitative and morphometric evaluation. RESULTS: At baseline,
      neuroretinal rim area was significantly (P < 0.03) smaller and the beta zone of
      parapapillary atrophy (temporal lower sector) was significantly (P < 0.03) larger
      in the hemorrhagic group than in the stable group. Both study groups did not vary
      significantly (P > 0.05) in optic disc size and shape, optic cup depth, alpha
      zone of parapapillary atrophy, and retinal vessel diameter. In multivariate
      analysis, the neuroretinal rim area was the only significant predictor of
      hemorrhages. The hemorrhagic group and the rim loss group did not differ
      significantly (P > 0.05) in any optic disc parameter measured. CONCLUSIONS: In
      chronic open-angle glaucoma, morphologic predictive factors for the development
      of disc hemorrhages are small size of neuroretinal rim and, possibly, a large
      parapapillary beta zone. Development of disc hemorrhages is independent of optic
      disc size and shape, size of alpha zone of parapapillary atrophy, retinal vessel
      diameter, and optic cup depth. Optic nerve heads in eyes with eventual
      development of disc hemorrhages and in eyes with eventual progressive rim loss
      without observed disc hemorrhages do not differ markedly in appearance.

PMID- 12202516
TI  - Detection of early neuron degeneration and accompanying microglial responses in
      the retina of a rat model of glaucoma.
AB  - PURPOSE: To characterize the early reaction of retinal ganglion cells (RGCs) in a
      rat model of glaucoma using in vivo imaging and to examine the involvement of
      retinal microglia in glaucomatous neuropathy. METHODS: Glaucoma was induced in
      adult female Sprague-Dawley rats by cauterizing two episcleral veins, which
      resulted in a 1.6-fold increase in intraocular pressure (IOP). Retinal ganglion
      cells were retrogradely labeled with the fluorescent dye, 4-[didecylaminostyryl]
      N-methyl-pyridinium-iodide (4-Di-10ASP) and monitored in vivo after elevation of
      IOP using fluorescence microscopy imaging. The number of RGCs was quantified on
      retinal flatmounts. Dying RGCs were surrounded by activated microglia that became
      visible after taking up the fluorescent debris. Immunocytochemistry was conducted
      to characterize further the ganglion cells and microglia. RESULTS: Cauterizing
      two of the four episcleral veins resulted in a consistent increase of IOP to 25.3
      +/- 2.0 mm Hg, as measured with a handheld tonometer. IOP remained high for at
      least 3 months in glaucomatous eyes. The earliest sign of RGC death was detected
      in anesthetized animals 20 hours after induction of glaucoma. RGCs continued to
      decrease in number over time, with 40% of RGCs having degenerated after 2.5
      months. Fundoscopic examination of the optic nerve head revealed cupping 2 months
      after induction of glaucoma. In addition, microglia were detected on retinal
      flatmounts as early as 72 hours after induction. Activated microglia and RGCs
      were also identified immunocytochemically, with an antibody against ionized
      calcium-binding adaptor molecule (Iba)-1 and an antibody specific to the 200-kDa
      subunit of the neurofilament protein, respectively. CONCLUSIONS: Occlusion of
      episcleral veins is a reproducible method that mimics human glaucoma, with
      chronically elevated IOP-induced RGC loss. This study shows that in vivo imaging
      permits the detection of ganglion cells in the living animal in the early stages
      of the disease and highlights the importance of in vivo imaging in understanding
      ophthalmic disorders such as glaucoma. Secondly, activation of intraretinal
      microglia coincides with degeneration of RGCs in glaucoma.

PMID- 12202517
TI  - Effect of intraocular pressure on optic disc topography, electroretinography, and
      axonal loss in a chronic pressure-induced rat model of optic nerve damage.
AB  - PURPOSE: To characterize the effect of intraocular pressure (IOP) on optic disc
      topography, retinal function, and axonal survival in a model of IOP-induced optic
      nerve damage in rat. METHODS: Hypertonic (1.75 M) saline was injected into an
      episcleral vein of one eye of 49 Brown Norway rats, with the fellow untreated eye
      serving as the control. During the 1 to 3 months of follow-up, IOP was measured
      twice weekly in conscious animals with a handheld tonometer, and changes in disc
      topography and retinal function were monitored with scanning laser tomography and
      electroretinography (ERG), respectively. Peak IOP elevation in the experimental
      eye compared with the fellow control eye (peak deltaIOP), integral of IOP
      elevation over time (deltaIOP integral), and days of IOP elevation were
      calculated. Axon counts were obtained from electron micrographs of the sectioned
      optic nerves. RESULTS: Progressive cupping was found in 9 (56.3%) of 16 eyes with
      peak deltaIOP of more than 15 mm Hg and in none of 21 eyes with peak deltaIOP
      less than 15 mm Hg. A strong correlation between deltaIOP integral and
      progressive cupping was also found, but not with days of IOP elevation. ERG
      abnormalities (limited to the b-wave) were found in 11 (64.7%) of 17 eyes with
      peak deltaIOP of more than 15 mm Hg and in 2 (8.7%) of 23 eyes with peak deltaIOP
      of less than 15 mm Hg. Neither of the other IOP parameters was predictive of ERG
      damage. The proportion of surviving axons was negatively correlated to both
      deltaIOP and deltaIOP integral (P <or= 0.001). Progressive cupping was evident
      only with more than 55% axonal loss. Similarly, ERG results remained mostly
      within normal limits for low to moderate axonal loss, but were markedly abnormal
      with more than 70% axonal loss. CONCLUSIONS: Structural and functional changes in
      this model are best correlated to peak deltaIOP and not to duration of IOP
      elevation, suggesting the existence of an IOP-related damage threshold.

PMID- 12202518
TI  - Role of enhanced expression of m-CSF in conjunctiva affected by cicatricial
      pemphigoid.
AB  - PURPOSE: Local proliferation of macrophages has been reported to augment the
      inflammatory response in various human and experimental diseases. Macrophage
      accumulation in the submucosa is also an important feature in the pathogenesis of
      ocular cicatricial pemphigoid (OCP). In the present study, the role of local
      proliferation of macrophages in conjunctiva affected by OCP and the relationship
      between local proliferation of macrophages and expression of macrophage-colony
      stimulating factor (m-CSF) in such conjunctiva were examined. METHODS: Biopsy
      specimens from the conjunctiva of 10 untreated patients with active OCP and from
      5 normal subjects were studied for the expression of m-CSF, macrophages, and
      proliferating cell nuclear antigen (PCNA), a cell cycle protein, by
      immunohistochemistry. Dual staining for CD68 (a cell surface marker for
      macrophages) and PCNA was also performed to identify proliferating macrophages.
      In addition, fibroblasts isolated from conjunctiva of normal individuals and from
      patients with OCP were studied for the expression of m-CSF by immunostaining and
      real-time PCR. To identify the factors that induce m-CSF in conjunctival
      fibroblasts, the fibroblasts were incubated with different concentrations of
      interleukin (IL)-1alpha and tumor necrosis factor (TNF)-alpha, and the levels of
      m-CSF mRNA were determined by real-time PCR and the amount of m-CSF produced was
      determined by enzyme-linked immunosorbent assay (ELISA). RESULTS: Normal
      conjunctiva showed weak expression of m-CSF in the conjunctival epithelial cells
      and stroma. Conjunctival expression of m-CSF protein was significantly (P <
      0.0001) increased in conjunctival biopsy specimens from patients with OCP. m-CSF
      was detected in the infiltrating macrophages, stromal cells (presumably
      fibroblasts), and conjunctival epithelial cells. Compared with normal control
      conjunctival tissue, a 1.2-fold increase in the expression of mRNA for m-CSF was
      detected by real-time PCR in the conjunctival tissue obtained from patients with
      OCP. Increased expression of m-CSF correlated significantly (P < 0.0004) with an
      increased stromal accumulation of macrophages in conjunctival biopsy specimens of
      patients with OCP. A number of these accumulated macrophages (CD68-positive) were
      found to be proliferating (PCNA-positive). In addition, fibroblasts isolated and
      cultured from conjunctiva of patients with OCP showed significantly increased
      (1.7-fold) expression of m-CSF compared with normal conjunctival fibroblasts.
      When conjunctival fibroblasts were treated with IL-1alpha or TNF-alpha, real-time
      PCR and ELISA detected an increased level of m-CSF. CONCLUSIONS: An increased
      expression of m-CSF was observed in conjunctiva from patients with active OCP.
      There was a positive correlation between expression of m-CSF and accumulation of
      macrophages in conjunctival biopsy sections obtained from patients with OCP.
      Increased expression of m-CSF, mainly by conjunctival fibroblasts and
      infiltrating inflammatory cells, may play an important role in the regulation of
      local proliferation of macrophages in OCP. In the conjunctiva of patients with
      OCP, this process could augment or enhance the local inflammatory response and
      tissue injury consequent to it.

PMID- 12202519
TI  - Spontaneous induction of immunoregulation by an endogenous retinal antigen.
AB  - PURPOSE: Ocular immune deviation studies have relied on intraocular injections of
      antigen to induce altered immune responses. Contributions of the injection
      process itself have complicated study of the mechanisms and interpretations of
      biological significance. In the current study, transgenic mice were used to
      determine the presence of immune deviation or other evidence of immunoregulation,
      elicited by endogenous Escherichia coli beta-galactosidase (beta-gal) expressed
      through a retinal arrestin promoter. METHODS: Mice that express beta-gal in the
      retina and various control mice were immunized with beta-gal and tested for
      immune responsiveness by the ear-swelling test for delayed-type hypersensitivity
      (DTH), in vitro proliferation assays, and cytokine assays. Spleen cells from
      transgenic mice were also transferred to normal recipients to test for transfer
      of immune deviation. RESULTS: Endogenous retinal beta-gal expression depressed
      the DTH response and proliferation assays after beta-gal immunization. The
      ability to depress DTH was transferred by naive spleen cells from transgenic mice
      to nontransgenic mice. Use of an immunization protocol that included high-dose
      Mycobacterium tuberculosis (M tb) H37Ra adjuvant and concurrent administration of
      pertussis toxin reversed the inhibition of DTH. CONCLUSIONS: An endogenous neo
      self-retinal antigen alters subsequent immune responses without intraocular
      injection, suggesting that normal retinal proteins in quiet eyes induce
      immunoregulatory responses. Based on cytokine assays, there were similarities to
      the immune deviation induced by intraocular inoculation in the IL-4 response, but
      the IL-10, IFN-gamma, and TGF-beta1 results were not similar, indicating that the
      mechanisms differ. The ability of supplemented adjuvant to overcome endogenous
      tolerance may be related to the requirement for supplemented adjuvants in the
      induction of experimental autoimmune uveoretinitis.

PMID- 12202520
TI  - IL-4 and IL-13 regulation of ICAM-1 expression and eosinophil recruitment in
      Onchocerca volvulus keratitis.
AB  - PURPOSE: The presence of eosinophilic granulocytes in ocular tissue is a hallmark
      of the host response to environmental and parasite allergens. Using a mouse model
      of Onchocerca volvulus-mediated keratitis (river blindness), the present study
      examined the role of the cytokines interleukin (IL)-4 and IL-13 in regulating
      recruitment of eosinophils to the cornea through expression of intercellular cell
      adhesion molecule (ICAM)-1. METHODS: C57BL/6 mice received an intrastromal
      injection of recombinant IL-4 and IL-13 (rIL-4 and IL-13) or were immunized by
      subcutaneous injection prior to receiving an intrastromal injection of a soluble
      O. volvulus extract. Expression of ICAM-1 and recruitment of eosinophils to the
      cornea were monitored by immunohistochemistry. RESULTS: Expression of ICAM-1 was
      elevated after injection of rIL-4 or IL-13 together with recombinant tumor
      necrosis factor (rTNF)-alpha. Conversely, expression of ICAM-1 in O. volvulus
      mediated keratitis was significantly reduced after subconjunctival injection of a
      monoclonal antibody (mAb) to IL-4 or IL-13. In addition, combined in vivo
      neutralization of IL-4 and IL-13 inhibited recruitment of eosinophils, but not of
      neutrophils, to the corneal stroma. CONCLUSIONS: These findings demonstrate that
      expression of ICAM-1 and recruitment of eosinophils to the cornea are tightly
      regulated by IL-4 and IL-13, and indicate that these cytokines are a potential
      target for immune intervention in ocular allergy and parasitic infections of the
      eye.

PMID- 12202521
TI  - Crygf(Rop): the first mutation in the Crygf gene causing a unique radial lens
      opacity.
AB  - PURPOSE: The Rop (radial opacity) mutation, which was recovered in a mutagenicity
      screen after paternal treatment with procarbazine, was analyzed to determine
      phenotype, chromosomal localization, candidate genes, and molecular lesion.
      METHODS: Native lenses were photographed under a dissecting microscope.
      Histologic sections of the eye were made according to standard procedures. Fine
      mapping of the mutation in relation to microsatellite markers for mouse
      chromosome 1 was performed. Candidate genes were amplified by PCR from cDNA or
      genomic DNA and sequenced. RESULTS: The nuclear opacity of the heterozygous
      mutants showed radial structures, whereas the opacity of the homozygotes was
      homogenous. The histologic analysis revealed changes in the lens nucleus, which
      corresponds to the pronounced opacification in lenses of homozygous mutants. The
      allelism of Rop to the Cat2 group of dominant cataracts on mouse chromosome 1 was
      confirmed by linkage to microsatellite markers D1Mit156 and D1Mit181. The cluster
      of the Cryg genes and the closely linked Cryba2 gene were tested as candidates. A
      T-->A exchange in exon 2 of the Crygf gene leads to a Val-->Glu exchange in codon
      38 and was considered to be causative for the cataract phenotype; therefore,
      Crygf(Rop) has been suggested as the designation for the mutation. CONCLUSIONS:
      Crygf(Rop) is the first mutation affecting the Crygf gene. Dominant cataract
      mutations for all six Cryg genes on mouse chromosome 1 have now been
      characterized, demonstrating the importance of this gene cluster in lens
      transparency.

PMID- 12202522
TI  - Derivation of lenticular transmittance from fluorophotometry.
AB  - PURPOSE: To derive transmittance spectra for the human lens using the ratio
      between posterior and anterior autofluorescence of the lens as measured by
      fluorophotometry. METHODS: Transmittance spectra of the lens can be described
      with a one-parameter model to a high degree of accuracy. The parameter m of this
      model defines the differences between lens transmittance spectra of individuals.
      In fluorophotometry literature another parameter related to lens transmittance,
      T, has been defined as the square root of the ratio between posterior and
      anterior lenticular autofluorescence. T can be predicted from parameter m, given
      the spectra of the excitation light, of the fluorescence emitted by the lens and
      of the detecting device are known, and assuming that the anterior and posterior
      fluorescence efficiencies of the lens are equal. When this relation is inverted,
      parameter m can be derived from T, giving the complete transmittance spectrum on
      the basis of T. RESULTS: A transformation curve was calculated to determine T
      from m and vice versa. The light transmittance spectrum of the lens was
      calculated as a function of T. The validity of this approach was evaluated using
      an independent method for assessment of lenticular transmittance. This method
      consisted of making color slitlamp slides, grading the observed color of these
      slides with the LOCS III NC grading system, and transforming these grades into
      the model parameter m using published transformation curves. CONCLUSIONS: The
      total transmittance spectrum can be calculated reliably from a fluorophotometric
      scan of the human lens.

PMID- 12202523
TI  - Molecular identification of P-glycoprotein: a role in lens circulation?
AB  - PURPOSE: To determine whether P-glycoprotein is expressed in the rat lens and to
      assess what type of damage occurs when P-glycoprotein inhibitors are applied to
      organ-cultured lenses. METHODS: An initial screening for the P-glycoprotein
      isoforms multidrug resistance (mdr)1a, mdr1b, and mdr2 was performed by RT-PCR on
      RNA extracted from rat lens fiber cells. Northern blot analysis was used to
      determine whether transcript levels detected by RT-PCR were significant. The
      presence of P-glycoprotein in the lens was confirmed by Western blot analysis and
      immunocytochemistry. Organ-cultured lenses, maintained in isotonic artificial
      aqueous humor, were exposed to various concentrations of the P-glycoprotein
      inhibitor tamoxifen. Lens opacification was assessed by dark-field microscopy,
      and the underlying cellular changes were visualized by confocal microscopy of
      lens sections, using a fluorescent membrane marker. Initial cellular damage was
      assessed after a 6-hour exposure to 100 micro M tamoxifen. Other P-glycoprotein
      inhibitors, verapamil, and 1,9-dideoxyforskolin (DDFK) were assessed, and the
      damage phenotypes were compared with those seen for tamoxifen. RESULTS:
      Transcript for all three P-glycoprotein isoforms was detected with RT-PCR, but
      only mdr1a and mdr2 could be detected by Northern blot analysis. P-glycoprotein
      was localized in the plasma membrane of lens epithelial and fiber cells.
      Treatment of organ-cultured lenses with increasing doses of the P-glycoprotein
      inhibitor tamoxifen for 18 hours showed that two distinct damage phenotypes were
      evident. At a dose of 20 micro M tamoxifen, tissue damage was found in a discrete
      zone that initially started approximately 100 micro m from the capsule, whereas
      at higher doses (60-100 micro M tamoxifen), extensive vesiculation of fiber cell
      membranes occurred throughout the entire lens cortex. Decreasing tamoxifen (100
      micro M) exposure to 6 hours showed that the inner zone of damage was caused by
      the dilation of extracellular space between fiber cells. The extracellular space
      dilution and fiber cell vesiculation could be reproduced by varying the
      concentrations of other P-glycoprotein inhibitors, verapamil and DDKF.
      CONCLUSIONS: The P-glycoproteins mdr1a and mdr2 are expressed in the lens and
      appear to be functional. The initial cellular damage phenotype of extracellular
      space dilations caused by the P-glycoprotein inhibitors was identical with that
      caused by chloride channel inhibitors, indicating that P-glycoprotein may play a
      role in regulating cell volume in the lens. Whether the secondary damage
      phenotype of fiber cell vesiculation, induced by high doses of P-glycoprotein
      inhibitors, was due to the inhibition of additional regulatory activities of P
      glycoprotein or to nonspecific effects of the drugs remains to be determined.
      However, regardless of the precise mode of action, these results indicate that P
      glycoprotein should be considered in the regulatory mechanisms associated with
      the control of lens volume and in the initiation of osmotic cataract.

PMID- 12202524
TI  - Adenosine A1 receptor modulation of MMP-2 secretion by trabecular meshwork cells.
AB  - PURPOSE: Studies have shown that adenosine A(1) agonists can lower IOP in
      rabbits, mice, and monkeys, and this response is mediated in part by increases in
      outflow facility. The purpose of this project was to evaluate the response of
      trabecular meshwork cells to the addition of the adenosine A(1) receptor agonist
      N(6)-cyclohexyladenosine (CHA). METHODS: The human trabecular meshwork (HTM-3)
      cell line and primary cultures of bovine trabecular meshwork (BTM) cells were
      used in these studies. Cells were treated with CHA, and the secretion of matrix
      metalloproteinase (MMP)-2 or the activation of extracellular signal-regulated
      kinase (ERK1/2) was determined. RESULTS: Treatment of HTM-3 and BTM cells with
      CHA (0.1 micro M) resulted in a time-dependent secretion of MMP-2 that was
      measurable as early as 30 minutes after treatment and reached a maximum by 2
      hours. This CHA-induced secretion of MMP-2 was inhibited by the adenosine A(1)
      receptor antagonist 8-cyclopentyl-1,3-dimethylxanthine (CPT) and by the ERK1/2
      pathway inhibitor U0126. Treatment of HTM-3 cells with CHA produced a rapid dose
      dependent activation of ERK1/2 with an EC(50) of 5.7 nM. The CHA-induced
      activation of ERK1/2 was inhibited by pretreatment with the adenosine A(1)
      antagonist CPT and by the ERK pathway inhibitor U0126. CONCLUSIONS: The addition
      of the adenosine A(1) agonist CHA stimulates the secretion of MMP-2 from
      trabecular meshwork cells. This secretory response involves the activation of
      adenosine A(1)-linked stimulation of ERK1/2. These results provide evidence for
      the existence of functional adenosine A(1) receptors in the trabecular cells and
      that the activation of these receptors stimulates secretion of MMP-2.

PMID- 12202525
TI  - Knockout of A3 adenosine receptors reduces mouse intraocular pressure.
AB  - PURPOSE: To test the putative role of A(3) adenosine receptors (ARs) in
      modulating intraocular pressure (IOP). METHODS: IOP was monitored for up to 32
      minutes in A3-knockout (A3AR-/-) and A3AR+/+ control mice by the servo-null
      approach. The IOP responses to adenosine, A3AR agonists and A3AR antagonists were
      studied singly or in combination in both strains. RESULTS: IOP was significantly
      lower in A3AR-/- mice (12.9 +/- 0.7 mm Hg) than in A3AR+/+ control animals (17.4
      +/- 0.6 mm Hg). The nonselective AR agonist adenosine produced a much smaller
      increase in IOP (2.2 +/- 0.8 mm Hg) in the knockout than in A3AR+/+ control mice
      (14.9 +/- 2.4 mm Hg). The A3-selective agonist IB-MECA did not affect IOP in A3
      knockout mice, but raised it in A3AR+/+ mice. The highly selective A3AR
      antagonist MRS 1191 did not affect IOP in A3AR-/- mice, but lowered it in A3AR+/+
      control mice. Preadministering MRS 1191 did not affect the small adenosine
      triggered increase in IOP in A3AR-/- mice, but markedly attenuated adenosine's
      effects on IOP in A3AR+/+ control mice. MRS 1523, an A3AR antagonist less
      selective than MRS 1191 in rats, decreased IOP in both A3AR-/- and A3AR+/+
      animals. As in black Swiss outbred mice and other mammalian species, reducing
      aqueous humor inflow with acetazolamide lowered IOP and administering water
      intraperitoneally increased IOP in both A3AR-/- and A3AR+/+ mice. CONCLUSIONS:
      The reduced IOP and altered purinergic responses of IOP in A3AR knockout mice
      support the conclusion that A3ARs contribute to the regulation of IOP.

PMID- 12202526
TI  - Disease progression in patients with dominant retinitis pigmentosa and rhodopsin
      mutations.
AB  - PURPOSE: To measure the rate of progression of retinal degeneration in patients
      with retinitis pigmentosa due to dominant rhodopsin mutations and to determine
      whether the rate of progression correlates with the location of the altered amino
      acid in the rhodopsin molecule. METHODS: Change in ocular function was observed
      for an average of 8.7 years in 140 patients. After censoring data to eliminate
      "ceiling" and "floor" effects, longitudinal rates of change were compared, after
      weighting by follow-up time and number of visits, with rates inferred from cross
      sectional analyses of the data from baseline visits. Mean rates of change were
      compared among groups of patients with mutations affecting the globule, plug, or
      C-terminal region of the protein after adjusting for age, gender, and baseline
      function. RESULTS: Mean annual exponential rates of decline were 1.8% for visual
      acuity, 2.6% for visual field area, and 8.7% for ERG amplitude. The rates of
      visual acuity and ERG amplitude decline were significantly faster, and the rate
      of visual field area decline was significantly slower, than those inferred from
      baseline visits. Rates of acuity loss did not vary significantly with the region
      affected by the mutation. In contrast, the mean annual rate of field loss in the
      C terminus group (7.4%) was significantly faster than that in the globule (1.7%)
      or plug (1.1%) group. The mean annual rate of ERG decline was also significantly
      faster in the C terminus group (13.5%) than in the globule (8.5%) or plug (3.7%)
      groups and significantly faster in the globule group than in the plug group.
      CONCLUSIONS: Rates of decline in visual function for groups of patients with
      rhodopsin mutations cannot be accurately inferred from cross-sectional analyses
      of baseline visits. Average rates of decline of visual field area and ERG
      amplitude are fastest in patients with mutations affecting the C-terminal region.

PMID- 12202527
TI  - The effect of nitric oxide on retinal blood flow during hypoxia in cats.
AB  - PURPOSE: To investigate how nitric oxide (NO) contributes to the regulation of
      retinal circulation during rest and hypoxia in cats. METHODS: N(G)-nitro-L
      arginine-methyl ester (L-NAME; n = 7), an NO synthase inhibitor; N(G)-nitro-D
      arginine methyl ester (D-NAME; n = 6), the inactive isomer; or phosphate-buffered
      saline (PBS; n = 7) was injected intravitreously. Hypoxia was induced in the cats
      by the administration of 10% oxygen. Vessel diameter and blood velocity were
      measured simultaneously in the anesthetized cats with a laser Doppler velocimetry
      system, and the retinal blood flow (RBF) and wall shear rate (WSR) were
      calculated as an index of shear stress on the retinal vessel wall. RESULTS: After
      intravitreous injection of L-NAME, the vessel diameter (-8.1% +/- 2.0%, P <
      0.01), velocity (-17.0% +/- 3.7%, P < 0.01), and RBF (-29.4% +/- 4.6%, P < 0.01)
      significantly decreased compared with the preinjection level. In the PBS group,
      maximum increases above the prehypoxia diameter (13.7% +/- 3.5%, P < 0.01),
      velocity (39.5% +/- 8.6%, P < 0.01), RBF (73.9% +/- 10.6%, P < 0.01), and WSR
      (28.3% +/- 7.1%, P < 0.01) were observed during hypoxia. In the L-NAME group,
      those changes substantially decreased in response to hypoxia. D-NAME was inactive
      with regard to RBF during rest and hypoxia. CONCLUSIONS: These results suggest
      that NO may be continuously produced in the retina during rest and contributes to
      increased RBF during hypoxia. In addition, the increased WSR during hypoxia
      indicates that NO plays an important role in retinal hypoxic hyperemia through a
      flow-induced mechanism.

PMID- 12202529
TI  - Increased spontaneous retinal ganglion cell activity in rd mice after neural
      retinal transplantation.
AB  - PURPOSE: To study the functional success of neural retinal transplantation by
      means of retinal surface ganglion cell recordings. METHODS: Eight-week-old
      C3H/HeJ (rd/rd) retinal degeneration mice received transplants (subretinal) in
      one eye only of neural retinal tissue isolated from newborn normal C57/BL6J mice.
      Four weeks after transplantation, ganglion cell responses were recorded directly
      from the retinal surface over the transplant, with a differential bipolar surface
      electrode. Measurements were performed, both with and without light stimulation.
      Similar recordings were performed in nontransplant areas of the transplant
      recipient eyes, and in age-matched sham-treated and untreated control eyes. After
      the recordings, the eyes were processed for light and transmission electron
      microscopy. RESULTS: Histologic examination showed that in some areas,
      transplanted cells were organized into small sheets and differentiated into
      photoreceptors with outer segments in intimate contact with the host RPE. No
      light-driven ganglion cell responses were recordable from the transplant
      recipient or control eyes. However, the spontaneous ganglion cell activity was
      higher in the transplant areas (mean: 10.8 +/-12.0 spikes/1.6 sec) compared with
      nontransplant areas of these recipient eyes (mean: 2.4 +/- 5.7spikes/1.6 sec; P <
      0.001), sham-treated eyes (mean: 2.5 +/- 4.8 spikes/1.6 sec; P < 0.001), and the
      untreated control eyes (mean: 2.2 +/- 4.4 spikes/1.6 sec; P < 0.001).
      CONCLUSIONS: Subretinal transplantation of neural retinal tissue results in a
      local increase of spontaneous ganglion cell activity. The increased activity may
      be due to the release of neurochemically active substances as a result of the
      presence of the transplant. Although light responses were not recordable, the
      technique of retinal surface ganglion cell recording may be useful for assessing
      the functional success of transplantation.

PMID- 12202528
TI  - Hemodynamic parameters in blood vessels in choroidal melanoma xenografts and rat
      choroid.
AB  - PURPOSE: Choroidal melanoma is the most common primary ocular cancer among the
      adult population. To avoid enucleation, there has been a concerted effort to
      develop therapies that spare the affected eye and the patient's vision. Blood
      flow helps shape the tumor's microenvironment, plays a key role in the tumor's
      response to many different types of therapy, and is necessary for delivery of
      chemotherapeutic agents. To rationally design new therapies and optimize existing
      treatments, it is essential to learn as much as possible about blood flow and the
      microcirculation in this tumor. In recent years, much has been discovered about
      the anatomy of the microvasculature and the dynamics of overall blood flow in
      choroidal melanoma, but little is known about the factors that determine
      microvascular blood flow. In this study hemodynamic parameters in individual
      microvessels of a human choroidal melanoma xenograft were compared with those
      same parameters in a normal rat choroid. METHODS: Nude, athymic WAG/RijHs-rnu
      rats were used in this study. The human choroidal melanoma cell line OCM-1 was
      used to grow solid tumors subcutaneously in the flanks of donor rats. Small
      pieces of these tumors were then implanted into the choroidal space of recipient
      rats. After 6 to 8 weeks, the rats were anesthetized with a subcutaneous
      injection of urethane, and the sclera was exposed. Rhodamine-labeled liposomes
      and red blood cells (RBCs) labeled with 1,1'-dioctadecyl-3,3,3',3'
      tetramethylindocarbocyanine perchlorate (DiI) were injected intravenously.
      Epifluorescent, intravital microscopy was used to visualize the flow of
      fluorescent RBCs through individual vessels in the choroid or tumor. Flow through
      multiple vessels was recorded on videotape for later analysis. From the
      recordings, RBC flux, RBC velocity (V(c)), and microvascular hematocrit (HCT(m))
      were determined. Similar experiments were performed in rats with no tumor growth,
      and these same parameters were calculated in normal choroidal vessels. RBC flow
      was characterized in 55 vessels in six OCM-1 tumors and in 153 choroidal vessels
      in five non-tumor-bearing rats. RESULTS: RBC flux was higher in larger tumor
      vessels (>30 micro m in diameter) compared with similarly sized choroidal
      vessels. There were no differences in the velocities of RBCs through the two
      types of vessels. HCT(m) was significantly higher in medium-sized (>20 micro m in
      diameter) and larger tumor vessels compared with normal choroidal vessels.
      CONCLUSIONS: These experiments demonstrate differences between hemodynamic
      parameters in normal choroidal microvessels and microvessels in choroidal
      melanoma in this animal model. Because HCT(m) is a key determinant of apparent
      viscosity, abnormally high HCT(m) in the tumor vessels would increase vascular
      resistance and decrease flow. This could have a negative impact on the tumor
      oxygen levels and on the ability to deliver drugs effectively. On the contrary,
      higher local HCT(m) has also been shown to increase oxygen delivery. The impact
      and interplay of these two effects on tumor oxygenation remain to be determined.

PMID- 12202530
TI  - Ischemic preconditioning attenuates apoptotic cell death in the rat retina.
AB  - PURPOSE: Ischemic preconditioning (IPC) protects the rat retina against the
      injury that ordinarily follows prolonged ischemia. It has been shown that release
      of adenosine, de novo protein synthesis, and mediators, such as protein kinase C
      and K(ATP) channels, is required for IPC protection. However, the molecular
      mechanisms of neuroprotection by IPC are unknown. Retinal cells die after
      ischemia by necrosis and apoptosis. This study was undertaken to investigate the
      effect of IPC on apoptosis after ischemia and some of the key proteins involved
      in the apoptotic cascade. METHODS: Retinal ischemia or IPC was produced in
      anesthetized Sprague-Dawley rats by increasing intraocular pressure above
      systolic arterial pressure. Retinal ischemia was induced 24 hours after either
      IPC or sham IPC. TUNEL staining was used to quantitate the number of cells with
      DNA fragmentation. The authors examined expression of cleaved forms of caspases-2
      and -3, bax, and poly-adenosine diphosphate-ribose-polymerase (PARP) by Western
      blot analysis for evidence of apoptosis-related gene expression. To examine
      possible mechanisms of apoptosis after ischemia, the authors studied the
      expression of mitogen-activated protein kinases (MAP kinases). Functional
      recovery after ischemia was measured using electroretinography, and retinal
      histology was examined and quantitated by light microscopy. RESULTS: Positive
      TUNEL staining, increases in caspase-2 and -3 cleavage, expression of bax and
      PARP, and activation of MAP kinases were found with ischemia. IPC attenuated
      these changes, but paradoxically, IPC itself triggered increased expression of
      MAP kinases. CONCLUSIONS: IPC protects against ischemic injury, in part, by
      diminishing apoptosis-related gene expression and by altering protein
      phosphorylation.

PMID- 12202531
TI  - Retinal hemangioblastoma in von Hippel-Lindau disease: a clinical and molecular
      study.
AB  - PURPOSE: To assess the natural history of retinal manifestations in von Hippel
      Lindau (VHL) disease and to study the genotype-phenotype correlation. METHODS:
      Data concerning 103 patients with VHL retinal manifestations and 108 patients
      without VHL retinal manifestations were extracted from the French VHL database. A
      retrospective study was performed by questionnaire. Patients were classified into
      three visual morbidity groups. Molecular analysis of the VHL gene was performed
      in 196 patients. RESULTS: The mean age of ocular manifestations detection was
      24.8 years. In half of the cases, the ocular manifestations revealed the disease.
      Half of the cases had bilateral involvement. Visual morbidity was significantly
      associated with the retinal hemangioblastoma count but not with other ocular or
      general characteristics. One third of the patients were classified in the worst
      visual morbidity group at the end of follow-up. Mutations were detected in 81% of
      patients with retinal hemangioblastomas and in 71% of patients without retinal
      involvement. Using a Poisson model and a marginal approach, the number of
      hemangioblastomas, age-adjusted, was 2.1 times higher in patients who had a
      substitution than in patients with a truncation (95% CI, 1.05-4.44; P < 0.05).
      CONCLUSIONS: Visual loss remains one of the major complications of VHL disease,
      confirming the importance of early ophthalmologic screening. Visual morbidity was
      not related to the type of extraocular manifestation but appeared to be related
      to the type of germline mutation. However, only further genetic and clinical
      studies in a larger series of patients will clearly determine the genotype
      phenotype relationship.

PMID- 12202532
TI  - Widespread expression of an exogenous gene in the eye after intravenous
      administration.
AB  - PURPOSE: Gene-targeting technology and tissue-specific gene promoters were used
      to produce widespread expression of an exogenous gene throughout the eye,
      including the retinal pigmented epithelium, after noninvasive intravenous
      administration of a nonviral plasmid formulation. METHODS: An expression plasmid
      encoding bacterial beta-galactosidase, under the influence of either the simian
      virus (SV)40 promoter or the glial fibrillary acidic protein (GFAP) gene
      promoter, was packaged in the interior of 85-nm pegylated immunoliposomes (PIL)
      targeted to transferrin receptor (TfR)-rich structures with the rat 8D3
      monoclonal antibody (mAb) to the mouse TfR. Plasmid DNA was packaged in the 8D3
      PIL and injected intravenously into adult female BALB/c mice at a dose of 5 micro
      g DNA per mouse. The eyes were removed 48 hours later, and frozen sections were
      prepared for beta-galactosidase histochemistry and rhodopsin, TfR, or GFAP
      immunocytochemistry. RESULTS: There was diffuse expression of the SV40/beta
      galactosidase gene in the retinal pigmented epithelium. The cellular specificity
      of gene expression was influenced by the promoter used in the gene construct,
      evidenced by the fact that gene expression in the inner retina was induced with
      the GFAP promoter. The beta-galactosidase gene was also widely expressed in the
      TfR-rich epithelial structures of the eye, including the ciliary body, the iris,
      the sebaceous glands of the tarsal plate, and the epithelium of the cornea. When
      the anti-TfR mAb on the PIL was replaced with the rat IgG isotype control, there
      was no gene expression in the eye. CONCLUSIONS: Widespread expression of an
      exogenous gene throughout the retina pigmented epithelium or other structures of
      the eye is possible with a noninvasive intravenous administration of a nonviral
      plasmid that is reformulated with gene-targeting technology. The cellular
      specificity of gene expression in the eye can be regulated with the use of cell
      specific gene promoters.

PMID- 12202533
TI  - Effect of polyamine depletion on cone photoreceptors of the developing rabbit
      retina.
AB  - PURPOSE: To measure the concentrations of polyamines, determine their cellular
      and subcellular localization, and analyze effects of their depletion in
      developing rabbit retina. METHODS: Isolated retinas at different developmental
      stages were analyzed for polyamine content by high-performance liquid
      chromatography (HPLC). An antibody against polyamines was used to localize
      endogenous stores in both freshly harvested retinas and neonatal retinal
      explants. To determine the effects of polyamine depletion on immature retina,
      neonatal explants were cultured in the presence or absence of alpha
      difluoromethylornithine (DFMO), an inhibitor of the polyamine synthetic enzyme
      ornithine decarboxylase (ODC). Similar studies were also performed on dissociated
      cell cultures. Tissue was assessed using standard histologic stains as well as
      cell-specific markers (peanut agglutinin for cone photoreceptors and calbindin
      for horizontal cells). RESULTS: Retinal polyamine content was highest at birth,
      remained relatively high during the first postnatal week, and then steadily
      decreased to adult levels. At all ages analyzed, spermine concentration was
      higher than putrescine or spermidine; however, the differential was greatest in
      the adult. Polyamine immunoreactivity was localized to distal processes of both
      rods and cones during development. Strong immunoreactivity was maintained in
      adult cone inner and outer segments; comparatively weak staining was observed in
      the adult rods. Heavy staining of ganglion cells was present throughout
      development but was localized in the cytoplasm in immature cells and in the
      nucleus in the adult. Amacrine cells stained only in the adult. Polyamine
      depletion caused a disruption of immature cones, evident in the loss of their
      somata in the outer nuclear layer, in their processes in the outer plexiform
      layer in retinal explants, and in their decreased association with horizontal
      cells in dissociated cell culture. CONCLUSIONS: The relatively high
      concentrations of polyamines in neonatal retina and their discrete localization
      in developing photoreceptor outer segments and ganglion cells suggests an
      important role for these compounds in development. The disruption of cone
      specific markers in polyamine-depleted retinas indicates a specific reliance on
      polyamines for expression of normal cone morphology or morphologic development.
      These developmental effects may involve polyamine-sensitive ion channels, which
      are known to exist in retina, or direct interactions with specialized
      cytoskeletal elements within outer segments.

PMID- 12202534
TI  - Activation and role of MAP kinase-dependent pathways in retinal pigment
      epithelial cells: ERK and RPE cell proliferation.
AB  - PURPOSE: Retinal pigment epithelial (RPE) cell proliferation plays a key role in
      the pathogenesis of ocular diseases involving the posterior segment. Mitogen
      activated protein kinases (MAPKs) are involved in the control of cell
      proliferation. This study was conducted to investigate the involvement of the
      extracellular signal-regulated kinase (ERK) pathway, the major MAPK pathway
      implicated in cell growth during the induction of RPE cell proliferation.
      METHODS: RPE cell proliferation was stimulated with 10% fetal calf serum (FCS).
      Activation of the Ras/Raf/MAP kinase-ERK kinase (MEK)/extracellular signal
      regulated kinase (ERK) signaling pathway was detected by Western blot analysis
      and immunochemistry with specific anti-phosphosignaling protein antibodies.
      Pharmacologic and antisense (AS) oligonucleotide (ODN) strategies were used to
      analyze the ERK signaling involved in serum-induced cell proliferation. RESULTS:
      FCS (10%) induced more vigorous RPE cell proliferation than did FGF2, VEGF,
      platelet-derived growth factor (PDGF), or epidermal growth factor (EGF), alone or
      in combination. Pharmacologic inhibition of Ras and Raf-1 reduced cell
      proliferation by 67% to 100% and by 62% to 79%, respectively, demonstrating that
      activation of the Ras/Raf-1 pathway was essential for FCS-induced RPE cell
      proliferation. MEK1/2, ERK2, and P90 ribosomal S6 kinase (P90(RSK)), the kinases
      downstream from ERK2, were strongly activated during cell proliferation.
      Pharmacologic inhibition of MEK1/2 abolished activation of ERK2, but reduced cell
      proliferation by only 32%, showing that MEK/ERK participates in the signaling
      involved in RPE cell growth. Both inhibition of ERK2 activation, which reduced
      cyclin D1 production, and inhibition of cyclin D1 by AS ODN decreased cell
      proliferation, suggesting that RPE cell proliferation is mediated by cyclin D1
      through ERK2. CONCLUSIONS: The requirement for Ras and the regulatory role of
      ERK2 in cyclin D1 production and in cell proliferation suggest that the
      Ras/Raf/MEK/ERK pathway plays a key role in the control of RPE cell
      proliferation. These data may have important implications for the development of
      more selective methods for the inhibition of retinal proliferation.

PMID- 12202535
TI  - Ciliary neurotrophic factor as a transient negative regulator of rod development
      in rat retina.
AB  - PURPOSE: Ciliary neurotrophic factor (CNTF) has been shown to inhibit the
      developmental expression of rod differentiation markers in rat retinal cultures.
      The present study was undertaken to investigate whether CNTF transiently inhibits
      rod differentiation or induces irreversible changes in the developmental fate of
      rod precursors. METHODS: The effects of CNTF on rod differentiation were
      monitored in organotypic slice cultures from early postnatal rat retinas by
      quantification of opsin-immunoreactive cells. The in vitro formation of the
      photoreceptor layer was analyzed by light and electron microscopy. The
      developmental expression of the CNTF receptor in photoreceptors was determined by
      immunoblot analysis. RESULTS: CNTF did not interfere with the generation of rod
      precursors, their morphologic differentiation, or the formation of the outer
      nuclear layer. Inhibition of rod differentiation was reversible. In the
      continuous presence of CNTF the number of opsin-positive cells increased at a
      normal rate but with a delay of 3 to 4 days. Developing rods became resistant to
      CNTF, both in vivo and in vitro, and this correlated temporally with the
      downregulation of CNTF receptor expression. Receptor downregulation was inhibited
      by CNTF in a dose-dependent manner. At higher CNTF concentrations with sustained
      receptor expression, the CNTF-induced decrease in opsin expression was
      accompanied by an increase in the expression of a bipolar cell marker in rod
      precursors located in the photoreceptor layer. CONCLUSIONS: These data indicate
      that, although rod precursors exhibit some phenotypic plasticity in the presence
      of CNTF, the factor does not induce a switch in the developmental fate of rod
      precursors but plays a role as a transient and reversible negative regulator of
      rod differentiation.

PMID- 12202536
TI  - Diabetes-induced dysfunction of the glutamate transporter in retinal Muller
      cells.
AB  - PURPOSE: A decrease in the ability of Muller cells to remove glutamate from the
      extracellular space may play a critical role in the disruption of glutamate
      homeostasis that occurs in the diabetic retina. Because this amino acid is toxic
      to retinal neurons and is likely to exacerbate oxidative stress, elucidation of
      the mechanisms by which glutamate levels are elevated in diabetes may help in the
      understanding of the pathogenesis of diabetic retinopathy. This study tested the
      hypothesis that the function of the glutamate transporter in Muller cells of the
      diabetic retina is compromised by a mechanism involving oxidation. METHODS:
      Muller cells were freshly isolated from normal rats and those made diabetic by
      streptozotocin injection. The activity of the Muller cell glutamate transporter,
      which is electrogenic, was monitored by the perforated-patch configuration of the
      patch-clamp technique. RESULTS: Four weeks after the onset of hyperglycemia, a
      significant dysfunction of the Muller cell glutamate transporter was detected.
      After 13 weeks of streptozotocin-induced diabetes, the activity of this
      transporter was decreased by 67%. Consistent with oxidation's causing this
      dysfunction, exposure to a disulfide-reducing agent rapidly restored the activity
      of the glutamate transporter in Muller cells of diabetic retinas. CONCLUSIONS:
      Early in the course of diabetic retinopathy, the function of the glutamate
      transporter in Muller cells is decreased by a mechanism that is likely to involve
      oxidation.

PMID- 12202538
TI  - Modulation of permeability and adhesion molecule expression by human choroidal
      endothelial cells.
AB  - PURPOSE: The therapeutic potential of TA, an anti-inflammatory glucocorticoid,
      for the treatment of exudative retinopathy has been examined in several
      independent clinical studies. The modulation of permeability and adhesion
      molecule expression of an epithelial cell line has been described in vitro, with
      the use of cytokines and triamcinolone acetonide (TA). In the current study, the
      influence of proinflammatory cytokines and TA on permeability and adhesion
      molecule expression in human choroidal endothelial cells (CECs) was investigated.
      METHODS: Human CEC isolates treated with IFNgamma, TNFalpha, and TA were
      evaluated by flow cytometry and immunocytochemistry for expression of
      intercellular adhesion molecule (ICAM)-1, vascular cell adhesion molecule (VCAM)
      1, and major histocompatibility complex (MHC)-I and -II. The effects of IFNgamma,
      TNFalpha, and TA on paracellular permeability of CEC monolayers were assessed in
      transendothelial cell resistance (TER) assays. RESULTS: Both IFNgamma and
      TNFalpha significantly upregulated expression of ICAM1 and MHC-I on CECs.
      Expression of VCAM1 was induced after stimulation with both IFNgamma and
      TNFalpha, whereas expression of MHC-II was induced only by stimulation with
      IFNgamma. Cytokine-induced expression of ICAM1, MHC-I, and MHC-II antigen by CECs
      was significantly downregulated by TA. IFNgamma stimulation also increased
      permeability of CEC monolayers, whereas subsequent TA treatment decreased
      permeability of CEC monolayers. CONCLUSIONS: Human CEC isolates provide a useful
      in vitro model to study choroidal neovascular membrane characteristics and their
      potential response to pro- and anti-inflammatory agents. In addition, the results
      indicate that TA has the capacity to reduce adhesion molecule expression and
      permeability of choroidal vessels in vitro, confirming its potential as a
      therapeutic agent for treatment of exudative macular degeneration.

PMID- 12202537
TI  - Effect of 2'-benzoyl-oxycinnamaldehyde on RPE cells in vitro and in an
      experimental proliferative vitreoretinopathy model.
AB  - PURPOSE: To investigate whether 2'-benzoyl-oxycinnamaldehyde (BCA) induces
      apoptosis in human retinal pigment epithelial (hRPE) cells and has an
      antiproliferative effect in a proliferative vitreoretinopathy (PVR) model in the
      rabbit. METHODS: Fifty percent growth inhibition doses of hRPE cells at 50%, 75%,
      and 100% confluence were determined by MTT assay. Apoptosis in hRPE cells induced
      by BCA was shown by DAPI staining. Expression of p53, p21, Bcl-2, GADD45, cyclin
      D, phospho-MAP kinase, cdk2, and Akt1 at various concentrations of BCA in
      cultured hRPE cells was examined by immunoblot analysis. In the efficacy study,
      2.0 x 10(5) rabbit RPE cells were injected into the vitreous cavity after gas
      compression, and the eyes subsequently received either sham injections or 600
      micro M BCA. Fundus examination was performed before and 1, 7, 14, 21, and 28
      days after BCA injection. The toxicity studies were conducted by the same
      protocol as used for the efficacy evaluation but without the RPE cell injection.
      Simultaneous electroretinograms were recorded on days 1, 7, 14, 21, and 28 after
      exposure to the drug. RESULTS: BCA treatment induced apoptosis in hRPE cells.
      Furthermore, an increase in p53 expression, phosphorylation of Bcl-2, and
      downregulation of Akt1 expression were observed in BCA-induced apoptotic cells.
      BCA effectively prevented the proliferation of rabbit RPE cells in the
      experimental PVR model. BCA exhibited a wide safety margin, showing no evidence
      of causing retinal toxicity, even at the 600- micro M concentration. CONCLUSIONS:
      The results of this study suggest that BCA effectively inhibits proliferation of
      RPE cells and has a very wide safety margin, indicating a potential therapeutic
      usefulness in treating PVR.

PMID- 12202539
TI  - Noise frame duration, masking potency and whiteness of temporal noise.
AB  - PURPOSE: Because of the limited contrast range, increasing the duration of the
      noise frame is often the only option for increasing the masking potency of
      external, white temporal noise. This, however, reduces the high-frequency cutoff
      beyond which noise is no longer white. This study was conducted to determine the
      longest noise frame duration that produces the strongest masking effect and still
      mimics white noise on the detection of sinusoidal flicker. METHODS: Contrast
      energy thresholds (E(th)) were measured for flicker at 1.25 to 20 Hz in strong,
      purely temporal (spatially uniform), additive, external noise. The masking power
      of white external noise, characterized by its spectral density at zero frequency
      N0, increases with the duration of the noise frame. RESULTS: For short noise
      frame durations, E(th) increased in direct proportion to N0, keeping the nominal
      signal-to-noise ratio [SNR = (E(th)/N0)(0.5)] constant at threshold. The masking
      effect thus increased with the duration of the noise frame and the noise mimicked
      white noise. When noise frame duration and N0 increased further, the nominal SNR
      at threshold started to decrease, indicating that noise no longer mimicked white
      noise. The minimum number of noise frames per flicker cycle needed to mimic white
      noise decreased with increasing flicker frequency from 8.3 at 1.25 Hz to 1.6 at
      20 Hz. CONCLUSIONS: The critical high-frequency cutoff of detection-limiting
      temporal noise in terms of noise frames per signal cycle depends on the temporal
      frequency of the signal. This is opposite to the situation in the spatial domain
      and must be taken into consideration when temporal signals are masked with
      temporal noise.

PMID- 12202540
TI  - Laboratory diagnosis of lower respiratory tract infections: controversy and
      conundrums.

PMID- 12202541
TI  - Emergence of Klebsiella pneumoniae isolates producing inducible DHA-1 beta
      lactamase in a university hospital in Taiwan.
AB  - Ten nonrepetitive clinical isolates of Klebsiella pneumoniae exhibiting an
      unusual inducible beta-lactam resistance phenotype were identified between
      January 1999 and September 2001 in a university hospital in Taiwan. In the
      presence of 2 micro g of clavulanic acid, the isolates showed a one to four
      twofold concentration increase in the MICs of ceftazidime, cefotaxime, and
      aztreonam but remained susceptible to cefepime (MICs, </=0.5 micro g/ml) and
      imipenem (MICs, </=0.5 micro g/ml). PCR, sequence analysis, and isoelectric
      focusing revealed production by these isolates of TEM-1, SHV-11, and DHA-1, a
      plasmid-encoded inducible AmpC beta-lactamase originally found in a Salmonella
      enterica serovar Enteritidis strain. Transfer of the resistance by conjugation
      experiments was not successful, but Southern hybridization showed that bla(DHA-1)
      was located on 70-kb plasmids, suggesting that the bla(DHA-1)-containing plasmids
      in the K. pneumoniae isolates were non-self-transmissible. Five isolates were
      recovered from patients in two surgery wards and two intensive care units.
      Acquisition of the DHA-1 producers could be traced back to previous
      hospitalizations 1 to 5 months earlier for the other five patients. Six and seven
      patterns among the isolates were demonstrated by plasmid analysis and ribotyping,
      respectively, indicating that the spread of the DHA-1 producers was due to both
      horizontal transfer of bla(DHA-1) and dissemination of endemic clones.

PMID- 12202542
TI  - Hepatitis C virus genotyping: interrogation of the 5' untranslated region cannot
      accurately distinguish genotypes 1a and 1b.
AB  - Although the 5' untranslated region (5' UTR) is the most conserved region of the
      hepatitis C virus (HCV) genome, it has been suggested that interrogation of this
      region is sufficient for determination of the HCV genotype. We compared two
      methods of determination of the HCV genotype: (i) direct sequencing of the DNA of
      the NS-5b region and (ii) reverse line probe assay (LiPA; INNO-LiPA HCV II;
      Innogenetics N.V.) of the 5' UTR. There was 100% concordance between the two
      methods for genotype but only 80% concordance for subtype. A significant
      percentage of genotype 1a isolates were misclassified by LiPA as genotype 1b.
      Sequence analysis revealed that the only consistent difference in the 5' UTR for
      these genotype 1a isolates misclassified as genotype 1b was a single nucleotide
      (A/G) at position -99 of the HCV genome. All isolates with discordant results
      analyzed had a G at this position, consistent with LiPA determination of these
      samples as subtype 1b. However, sequence analysis of 222 nucleotides in the NS-5b
      region clearly identified all of these isolates as subtype 1a. Population
      distribution data from the University of Pittsburgh Medical Center of over 200
      samples analyzed by sequencing of the NS-5b region and over 1,000 samples
      analyzed by LiPA also indicated that INNO-LiPA HCV II cannot accurately
      differentiate HCV genotype 1a isolates from HCV genotype 1b isolates. We provide
      evidence that the A/G at position -99 represents a sequence polymorphism in the
      HCV genome that cannot differentiate subtype 1a from subtype 1b isolates. In
      conclusion, the 5' UTR is not heterogeneous enough for use in determination of
      the HCV subtype and cannot be used for differentiation of HCV genotypes 1a and
      1b.

PMID- 12202543
TI  - Replacement of Candida albicans with C. dubliniensis in human immunodeficiency
      virus-infected patients with oropharyngeal candidiasis treated with fluconazole.
AB  - Candida dubliniensis is an opportunistic yeast that has been increasingly
      implicated in oropharyngeal candidiasis (OPC) in human immunodeficiency virus
      (HIV)-infected patients but may be underreported due to its similarity with
      Candida albicans. Although most C. dubliniensis isolates are susceptible to
      fluconazole, the inducibility of azole resistance in vitro has been reported.
      Thus, the use of fluconazole prophylaxis in the treatment of these patients may
      have contributed to the increasing rates of isolation of C. dubliniensis. In this
      study, yeast strains were collected from the oral cavities of HIV-infected
      patients enrolled in a longitudinal study of OPC. Patients received fluconazole
      for the suppression or treatment of OPC, and isolates collected at both study
      entry and end of study were chosen for analysis. Samples were plated on CHROMagar
      Candida medium for initial isolation and further identified by Southern blot
      analysis with the species-specific probes Ca3 (for C. albicans) and Cd25 (for C.
      dubliniensis). Fluconazole MICs were determined by using NCCLS methods. At study
      entry, susceptible C. albicans isolates were recovered from oral samples in 42
      patients who were followed longitudinally (1 to 36 months). C. albicans strains
      from 12 of these patients developed fluconazole resistance (fluconazole MIC,
      >/=64 micro g/ml). C. dubliniensis was not detected at end of study in any of
      these patients. Of the remaining 30 patients, eight (27%) demonstrated a
      replacement of C. albicans by C. dubliniensis when a comparison of isolates
      obtained at baseline and those from the last culture was done. For the 22 of
      these 30 patients in whom no switch in species was detected, the fluconazole MICs
      for initial and end-of-study C. albicans isolates ranged from 0.125 to 2.0 micro
      g/ml. For the eight patients in whom a switch to C. dubliniensis was detected,
      the fluconazole MICs for C. dubliniensis isolates at end of study ranged from
      0.25 to 64 micro g/ml: the fluconazole MICs for isolates from six patients were
      0.25 to 2.0 micro g/ml and those for the other two were 32 and 64 micro g/ml,
      respectively. In conclusion, a considerable number of patients initially infected
      with C. albicans strains that failed to develop fluconazole resistance
      demonstrated a switch to C. dubliniensis. C. dubliniensis in this setting may be
      underestimated due to lack of identification and may occur due to the impact of
      fluconazole on the ecology of oral yeast species.

PMID- 12202544
TI  - Weak association between SEN virus viremia and liver disease.
AB  - Recently, a novel DNA virus designated SEN virus (SEN-V), which is thought to be
      related to posttransfusion hepatitis, was discovered. The aim of the present
      study was to clarify the relationship between SEN-V infection and the development
      of liver disease. We examined SEN-V from the sera of 21 patients with non-B, non
      C hepatocellular carcinoma (HCC) and 13 patients with non-B, non-C chronic liver
      disease (CLD) without HCC who were admitted to our hospital between 1995 and
      1997. Thirty-two patients without liver disease served as controls and were also
      examined for SEN-V. SEN-V DNA was detected by the nested PCR method after
      extraction of DNA from serum. SEN-V DNA was detected in 74% (25 of 34) of
      patients with CLD with or without HCC who were negative for both hepatitis B
      virus surface antigen and anti-hepatitis C virus antibody. SEN-V DNA was detected
      in 69% (9 of 13) of CLD patients without HCC and in 76% (16 of 21) of HCC
      patients. The prevalence of SEN-V was no higher in patients with liver disease
      than in patients without liver disease (24 of 32; 75%). There were no significant
      differences in age, sex, liver function, history of blood transfusion, or amount
      of alcohol intake between SEN-V-positive and SEN-V-negative CLD and HCC patients.
      Genetic analysis suggested that SEN-V is closely related to the TT virus family.
      SEN-V was detected at almost the same frequency in patients with and without
      liver disease. SEN-V does not seem to contribute either to the pathogenesis of
      liver disease or to the development of HCC from chronic liver disease.

PMID- 12202545
TI  - Cavitary pneumonia in an AIDS patient caused by an unusual Bordetella
      bronchiseptica variant producing reduced amounts of pertactin and other major
      antigens.
AB  - Although Bordetella bronchiseptica can infect and colonize immunocompromised
      humans, its role as a primary pathogen in pneumonia and other respiratory
      processes affecting those patients remains controversial. A case of cavitary
      pneumonia caused by B. bronchiseptica in an AIDS patient is presented, and the
      basis of the seemingly enhanced pathogenic potential of this isolate (designated
      814) is investigated. B. bronchiseptica was the only microorganism recovered from
      sputum, bronchoalveolar lavage fluid, and samples taken through the protected
      brush catheter. Unlike previous work reporting the involvement of B.
      bronchiseptica in cases of pneumonia, antibiotic treatment selected on the basis
      of in vitro antibacterial activity resulted in clearance of the infection and
      resolution of the pulmonary infiltrate. Although isolate 814 produced reduced
      amounts of several major antigens including at least one Bvg-activated factor
      (pertactin), the molecular basis of this deficiency was found to be BvgAS
      independent since the defect persisted after the bvgAS locus of isolate 814 was
      replaced with a wild-type bvgAS allele. Despite its prominent phenotype, isolate
      814 displayed only a modest yet a significant deficiency in its ability to
      colonize the respiratory tracts of immunocompetent rats at an early time point.
      Interestingly, the antibody response elicited by isolate 814 in these animals was
      almost undetectable. We propose that isolate 814 may be more virulent in
      immunocompromised patients due, at least in part, to its innate ability to
      produce low amounts of immunogenic factors which may be required at only normal
      levels for the interaction of this pathogen with its immunocompetent natural
      hosts.

PMID- 12202546
TI  - Detection of human papillomavirus DNA in urine specimens from human
      immunodeficiency virus-positive women.
AB  - Human immunodeficiency virus (HIV)-positive women may represent one of the
      fastest-growing populations at risk for acquiring cervical cancer and thus
      require frequent screening. The purpose of the present studies was to validate a
      PCR-based urine assay by comparing detection and genotyping of human
      papillomavirus (HPV) DNA in urine samples and matching cervical swab specimens of
      HIV-positive women. Despite a difference in amplifiability, the prevalence of any
      HPV genotype (58% for the cervical swab specimens and 48% for the urine
      specimens) was not significantly different in this population. The levels of
      concordance were 70, 71, and 78% for detection of any HPV type, any high-risk HPV
      type, or any low-risk HPV type in the two specimen types, respectively. While
      instances of discordant detection were greater for the cervical swab specimens
      than for the urine specimens, this was not statistically significant. The
      distributions of HPV genotypes were similar in the cervix and the urine for the
      majority of types examined. Importantly, detection of HPV DNA in urine was
      associated with an abnormal Papanicolaou smear to the same extent that detection
      of HPV DNA in a cervical swab specimen was. These data provide preliminary
      support for the proposal to use urine testing as a primary or secondary screening
      tool for cervical cancer in HIV-positive women or as an epidemiological tool.
      Additional studies with larger sample sizes must be conducted in order to further
      verify these findings.

PMID- 12202547
TI  - Reactive nitrogen intermediates have a bacteriostatic effect on Mycobacterium
      tuberculosis in vitro.
AB  - Susceptibility of six isolates of Mycobacterium tuberculosis (CB3.3, CDC1551,
      RJ2E, C.C.13, H37Rv, and H37Ra) and two isolates of Mycobacterium bovis (Ravenel
      and BCG) to reactive oxygen intermediates (ROI) and reactive nitrogen
      intermediates (RNI) was determined by standard in vitro survival assays. After 21
      days of incubation, the survival of most strains exposed to either acidified
      sodium nitrite (ASN) or hydrogen peroxide (H(2)O(2)) was significantly lower than
      the same strains unexposed to these RNI or ROI products. However, after 50 days
      of incubation, these differences in susceptibility became less apparent for
      strains exposed to ASN but not for strains exposed to H(2)O(2). The recovery of
      these strains after exposure to RNI suggests that the effect of RNI on M.
      tuberculosis is bacteriostatic. The in vitro concentrations of ROI and RNI used
      in these assays were higher than those expected in vivo. These observations
      suggest that, in vivo, RNI expression at physiologically achievable
      concentrations may keep M. tuberculosis from proliferating but that removal of
      RNI may allow the organisms to proliferate. Furthermore, the ability of some M.
      tuberculosis strains to cause rapidly progressive disease may relate to their
      intrinsic levels of RNI and ROI resistance.

PMID- 12202549
TI  - groESL sequence determination, phylogenetic analysis, and species differentiation
      for viridans group streptococci.
AB  - The full-length sequences of the groESL genes (also known as cpn10/60) of
      Streptococcus anginosus, Streptococcus constellatus, Streptococcus gordonii, and
      Streptococcus sanguis and the near full-length sequence of the groESL genes of
      Streptococcus intermedius, Streptococcus bovis, Streptococcus mitis,
      Streptococcus mutans, Streptococcus oralis, and Streptococcus salivarius were
      determined. The lengths of the groES genes from the 10 species listed above
      ranged from 282 to 288 bp, and the full-length sequences of groEL determined for
      4 species (S. anginosus, S. constellatus, S. gordonii, and S. sanguis) revealed
      that each was 1,623 bp. The intergenic region (spacer) between the groES and
      groEL genes varies in size (15 to 111 bp) and sequence between species. The
      variation of the groES sequences among the species tested was greater (62.1 to
      95.1% nucleotide sequence identities) than that of the groEL sequences (77.2 to
      95.2% nucleotide sequence identities). Phylogenetic analysis of the groES and
      groEL genes yielded evolutionary trees similar to the tree constructed by use of
      the 16S rRNA gene. The intraspecies variation of the spacer was minimal for
      clinical isolates of some species. The groESL sequence data provide an additional
      parameter for identification of viridans group streptococcal species.

PMID- 12202548
TI  - Detection of simian immunodeficiency virus in diverse species and of human
      immunodeficiency virus Type 2 by using consensus primers within the pol region.
AB  - Human immunodeficiency virus type 2 (HIV-2) is the result of cross-species
      transmission of simian immunodeficiency virus (SIV) from sooty mangabey monkeys
      to humans. Primer pairs (intHIV-2/SIV) based on a region of integrase that has
      considerable homology across HIV-2 and SIV lineages were designed to develop a
      broadly cross-reactive molecular assay to detect lentivirus infection in
      primates. The intHIV-2/SIV primers detect HIV-2 and simian viruses SIVcpz,
      SIVsmm, SIVsyk, SIVagm, and SIVmnd. The primers are also capable of amplifying
      some HIV-1 strains. Additionally, sequences from the integrase amplicons were of
      sufficient genetic diversity to permit not only phylogenetic clustering of all
      simian viruses to their respective lineages but also HIV type and group
      classification. Thus, the primers described here provide a method to detect
      primate lentiviruses from diverse species of nonhuman primates, as well as from
      persons infected with HIV-1 and HIV-2.

PMID- 12202550
TI  - Development and evaluation of rapid urinary antigen detection tests for diagnosis
      of penicilliosis marneffei.
AB  - Penicilliosis, caused by the dimorphic fungus Penicillium marneffei, is an
      important opportunistic systemic fungal infection affecting immunocompromised
      individuals living in areas where penicilliosis is endemic. We have demonstrated
      previously that a urinary enzyme-linked immunosorbent assay (ELISA) with purified
      rabbit polyclonal antibody against killed whole-fission-form arthroconidia of P.
      marneffei was specific and highly sensitive for the diagnosis of penicilliosis.
      In this study, a dot blot ELISA and a latex agglutination (LA) test were
      developed with the same polyclonal antibody and compared with the ELISA for the
      detection of P. marneffei urinary antigen. Urine specimens from 37 patients with
      culture-proven penicilliosis and 300 controls (52 healthy subjects and 248
      hospitalized patients without penicilliosis) were tested. Antigen was detected in
      urine from all 37 (100%) penicilliosis patients by the LA test, 35 (94.6%)
      penicilliosis patients by the dot blot ELISA, and 36 (97.3%) penicilliosis
      patients by the ELISA. False-positive results were found by the three assays for
      2 (0.7%), 8 (2.7%), and 6 (2%) of 300 controls, respectively. The overall
      sensitivities of the diagnostic tests were as follows: dot blot ELISA, 94.6%;
      ELISA, 97.3%; and LA test, 100% (specificities, 97.3, 98, and 99.3%,
      respectively). The LA test is simple, robust, rapid, and convenient and should
      prove to be an important addition to the existing diagnostic tests for
      penicilliosis.

PMID- 12202552
TI  - Identification of Anaplasma phagocytophila (formerly Ehrlichia phagocytophila)
      variants in blood from sheep in Norway.
AB  - A total of 41 blood samples were collected from 40 Anaplasma phagocytophila
      infected sheep in 11 sheep flocks from four different counties of southern
      Norway. The presence and nature of the Anaplasma species were identified by
      microscopic detection of morulae, PCR, reverse line blot hybridization, and 16S
      rRNA gene sequencing. A. phagocytophila was identified in all of the samples, and
      sequencing of the 16S rRNA gene revealed the presence of four variants of A.
      phagocytophila. Two of these variants have been described before, but two were
      newly identified 16S rRNA variants of this species. A. phagocytophila variant 1
      was found in nine flocks, A. phagocytophila variant 2 was found in four flocks,
      the A. phagocytophila prototype was found in two flocks, and A. phagocytophila
      variant 5 was found in one flock. In two flocks, some sheep were infected with A.
      phagocytophila variant 1, whereas others were infected with A. phagocytophila
      variant 2, and in three animals a double infection with two variants was
      registered. Analyses of the blood samples revealed that blood from sheep infected
      with A. phagocytophila variant 2 contained nearly twice as many neutrophils and
      eight times as many Anaplasma-infected neutrophils as blood from sheep infected
      with the A. phagocytophila variant 1. Furthermore, only 43% of the A.
      phagocytophila variant 2-infected sheep displayed antibody responses in an immune
      fluorescence assay, whereas 93% of the sheep with the A. phagocytophila variant 1
      infected sheep were seropositive.

PMID- 12202551
TI  - Molecular characterization of multiresistant d-tartrate-positive Salmonella
      enterica serovar paratyphi B isolates.
AB  - Since 1996, the National Salmonella Reference Laboratory of Germany has received
      an increasing number of Salmonella enterica subsp. enterica serovar Paratyphi B
      isolates. Nearly all of these belonged to the dextrorotatory tartrate-positive
      variant (S. enterica subsp. enterica serovar Paratyphi B dT(+)), formerly called
      S. enterica subsp. enterica serovar Java. A total of 55 selected contemporary and
      older S. enterica subsp. enterica serovar Paratyphi B dT(+) isolates were
      analyzed by plasmid profiling, antimicrobial resistance testing, pulsed-field gel
      electrophoresis, IS200 profiling, and PCR-based detection of integrons. The
      results showed a high genetic heterogeneity among 10 old strains obtained from
      1960 to 1993. In the following years, however, new distinct multiresistant S.
      enterica subsp. enterica serovar Paratyphi B dT(+) clones emerged, and one clonal
      lineage successfully displaced the older ones. Since 1994, 88% of the isolates
      investigated were multiple drug resistant. Today, a particular clone predominates
      in some German poultry production lines, poultry products, and various other
      sources. It was also detected in contemporary isolates from two neighboring
      countries as well.

PMID- 12202553
TI  - Comparison of rapid, automated ribotyping and DNA macrorestriction analysis of
      Burkholderia pseudomallei.
AB  - An automated ribotyping device (RiboPrinter) was used to determine the ribotypes
      of a collection of Burkholderia pseudomallei isolates. In a preliminary
      evaluation with the restriction enzymes BamHI and EcoRI, the protocol with EcoRI
      was more discriminating. The reproducibilities of the ribotypes obtained with
      EcoRI (EcoRI ribotypes) were determined by testing three levels of bacterial
      loads. The performance of the manufacturer's software was assessed by comparing
      the machine-optimized ribotypes with the type determined from the original gel
      image analyzed with Bionumerics software. The library of B. pseudomallei EcoRI
      ribotypes was then compared with the ribotypes obtained by DNA macrorestriction
      analysis of XbaI digests by pulsed-field gel electrophoresis. The typeability of
      B. pseudomallei by EcoRI ribotyping was 100%, and the discrimination index was
      0.94. The slightly greater discrimination provided by DNA macrorestriction
      analysis (0.96) was achieved at the expense of a significantly longer processing
      time of 6 days, although the method was only half the cost of automated
      ribotyping. Typeability by macrorestriction analysis was lower (97%) unless a
      thiourea step was added to neutralize the action of Tris-dependent endonucleases.
      The digital record of B. pseudomallei isolates analyzed thus far provides a
      useful resource for future epidemiological studies and will help shorten the
      response time in the event of a further melioidosis outbreak or the deliberate
      release of B. pseudomallei as a biohazard.

PMID- 12202554
TI  - Testing conditions for determination of minimum fungicidal concentrations of new
      and established antifungal agents for Aspergillus spp.: NCCLS collaborative
      study.
AB  - Standard conditions are not available for evaluating the minimum fungicidal
      concentrations (MFCs) of antifungal agents. This multicenter collaborative study
      investigated the reproducibility in three laboratories of itraconazole,
      posaconazole, ravuconazole, voriconazole, and amphotericin B MFCs for 15 selected
      isolates of Aspergillus spp. After MIC determinations for the 15 isolates in each
      center by the NCCLS M38-A broth microdilution method with four media, standard
      RPMI 1640 (RPMI), RPMI with 2% dextrose, antibiotic medium 3 (M3), and M3 with 2%
      dextrose, MFCs were determined for each isolate-medium-drug combination. MFCs
      were defined as the lowest drug dilutions that yielded <3 colonies (approximately
      99 to 99.5% killing activity). The highest reproducibility (96 to 100%) was for
      amphotericin B MFCs with the four media. Although reproducibility was more
      variable and medium dependent for the azoles (91 to 98%), agreement was good to
      excellent for itraconazole, ravuconazole, and voriconazole MFCs with RPMI and M3
      (93 to 98%). For posaconazole, the agreement was higher with M3 media (91 to 96%)
      than with RPMI media (91%). These data extend the refinement of testing
      guidelines for susceptibility testing of Aspergillus spp. and warrant
      consideration for introduction into future versions of the M38 document. The role
      of the MFC under these standardized testing conditions as a predictor of clinical
      outcome needs to be established in clinical trials.

PMID- 12202555
TI  - Polyphyletic strains of hepatitis E virus are responsible for sporadic cases of
      acute hepatitis in Japan.
AB  - Among 87 patients who were previously treated for acute hepatitis of unknown
      etiology between 1992 and 2001 at five hospitals in Japan, 11 (13%) patients were
      positive for immunoglobulin M-class antibodies to hepatitis E virus (HEV) by
      enzyme immunoassay and had detectable HEV RNA by reverse transcription-PCR with
      two independent sets of primers derived from well-conserved genomic areas in open
      reading frames 1 and 2. Clinical HEV infection was significantly associated with
      male sex (9 of 11 versus 29 of 76 patients [P < 0.01]) and older age (52 +/- 11
      [mean +/- standard deviation] versus 41 +/- 17 years [P < 0.05]), and its
      prevalence differed by geographic region (6 to 25%), with a higher rate in the
      northern part of Japan. At admission, the 11 patients with HEV-associated
      hepatitis had elevated alanine aminotransferase levels of 914 to 4,850 IU/liter,
      and all but 1 had elevated bilirubin levels of 1.5 to 24.0 mg/dl. The 11 HEV
      isolates were of genotype III or IV and were segregated into three groups with
      intergroup nucleotide differences of 9.5 to 22.0%. Phylogenetic analysis revealed
      that four isolates of genotype III were closely related to a Japanese isolate,
      while the other four isolates of the same genotype were nearest those from the
      United States. The remaining three isolates were close to known isolates of
      genotype IV in China and Taiwan but shared less than 88% identity with them.
      These results indicate that multiple genotypes of HEV cocirculate in Japan and
      contribute to the development of sporadic acute hepatitis, with the prevalence
      differing by age, sex, and geographic region.

PMID- 12202556
TI  - Comparison of C(18)-carboxypropylbetaine and standard N-acetyl-L-cysteine-NaOH
      processing of respiratory specimens for increasing tuberculosis smear sensitivity
      in Brazil.
AB  - Techniques to improve the sensitivity of smear microscopy would facilitate early
      tuberculosis (TB) diagnosis and disease control, especially in low-income
      countries where the positive predictive value is high. C(18)-carboxypropylbetaine
      (CB-18) is a zwitterionic detergent that helps to compensate for the innate
      buoyancy of mycobacteria, potentially enhancing recovery by centrifugation.
      Previous data suggest that CB-18 may increase the sensitivity of smear, culture,
      and molecular amplification diagnostic testing. The goal of the present study was
      to evaluate if the sensitivity of the smear technique using light microscopy
      could be improved by treating respiratory samples with CB-18. In the first phase,
      respiratory specimens were collected consecutively from patients with suspected
      pulmonary tuberculosis in a tertiary-care hospital in Rio de Janeiro, Brazil (236
      specimens were analyzed). After protocol modifications, another 120 respiratory
      specimens were evaluated. The standard technique was N-acetyl-L-cysteine with
      sodium hydroxide (NALC-NaOH) treatment, smear concentration with centrifugation,
      and Ziehl-Neelsen staining. Culture on Lowenstein-Jensen slants was performed on
      all specimens for use as the "gold standard." No specimens from patients
      undergoing active TB treatment were included. The initial protocol for CB-18
      processing resulted in a sensitivity of 59.6% and specificity of 96.8% compared
      to standard processing with a sensitivity of 66.0% and specificity of 96.8%.
      Using the modified protocol, the sensitivity of CB-18 increased to 71.4% with a
      specificity of 97.0% versus standard processing with a sensitivity of 61.9% and a
      specificity of 99.0%. The diagnostic yield of acid-fast bacillus smear with CB-18
      in the absence of fluorescence microscopy and PCR compared to standard processing
      with NALC-NaOH was not significantly different, although the power to detect a
      difference by the modified assay was low.

PMID- 12202557
TI  - PCR-based identification of bacteria associated with endodontic infections.
AB  - PCR primers that target the bacterial 16S rRNA genes (or the tuf gene for the
      genus Enterococcus) were used to identify 10 putative bacterial pathogens in root
      canals with necrotic pulp. In addition, the associations of these microorganisms
      with symptoms and a history of diabetes mellitus were investigated. Microbial
      samples from the root canals of 24 teeth with necrotic pulp were included in the
      study. PCR with universal bacterial primers identified bacterial DNA in 22
      specimens; the remaining 2 specimens were from intact teeth that had been
      traumatized 6 months prior to treatment. PCR with specific primers showed that
      preoperative symptoms were significantly associated with the presence of
      Streptococcus spp. (P < 0.001 by chi-square analysis). There was also a
      nonsignificant trend for symptoms to be associated with Fusobacterium nucleatum
      and Porphyromonas gingivalis (odds ratio, >2) and for diabetes mellitus to be
      associated with P. gingivalis and Porphyromonas endodontalis (odds ratio, >2).
      Cloning and sequencing of the universal PCR product in one specimen revealed the
      presence of an organism related to the genus Olsenella, which has not previously
      been described in endodontic infections.

PMID- 12202558
TI  - Sensitivity of three urinary antigen tests associated with clinical severity in a
      large outbreak of Legionnaires' disease in The Netherlands.
AB  - In 1999 an outbreak involving 188 patients with Legionnaires' disease (LD)
      occurred among visitors to a flower show in the Netherlands. Two enzyme
      immunoassays (Binax and Biotest) and one immunochromatographic assay (Binax NOW)
      were tested, using urine samples from LD patients from the 1999 outbreak.
      Sensitivity was calculated using positive culture and/or seroconversion as the
      "gold standard" in outbreak-related patients with radiographically confirmed
      pneumonia who fulfilled the epidemiological critera. The Binax EIA, Biotest EIA,
      and Binax NOW assay showed overall sensitivities of 69, 71, and 72%,
      respectively. When the tests were performed with concentrated urine samples, the
      overall sensitivities increased to 79, 74, and 81%, respectively. Using multiple
      logistic regression analysis with backward elimination, a statistically
      significant association was found between clinical severity and test sensitivity
      for all tests. For patients with mild LD, the test sensitivities ranged from 40
      to 53%, whereas for patients with severe LD who needed immediate special medical
      care, the sensitivities reached 88 to 100%. These findings have major
      implications for the diagnostic process in patients with mild pneumonia and
      suggest that patients with mild pneumonia may go underdiagnosed if urine antigen
      tests alone are used.

PMID- 12202559
TI  - Detection and genotyping of oocysts of Cryptosporidium parvum by real-time PCR
      and melting curve analysis.
AB  - Several real-time PCR procedures for the detection and genotyping of oocysts of
      Cryptosporidium parvum were evaluated. A 40-cycle amplification of a 157-bp
      fragment from the C. parvum beta-tubulin gene detected individual oocysts which
      were introduced into the reaction mixture by micromanipulation. SYBR Green I
      melting curve analysis was used to confirm the specificity of the method when DNA
      extracted from fecal samples spiked with oocysts was analyzed. Because C. parvum
      isolates infecting humans comprise two distinct genotypes, designated type 1 and
      type 2, real-time PCR methods for discriminating C. parvum genotypes were
      developed. The first method used the same beta-tubulin amplification primers and
      two fluorescently labeled antisense oligonucleotide probes spanning a 49-bp
      polymorphic sequence diagnostic for C. parvum type 1 and type 2. The second
      genotyping method used SYBR Green I fluorescence and targeted a polymorphic
      coding region within the GP900/poly(T) gene. Both methods discriminated between
      type 1 and type 2 C. parvum on the basis of melting curve analysis. To our
      knowledge, this is the first report describing the application of melting curve
      analysis for genotyping of C. parvum oocysts.

PMID- 12202560
TI  - Dichotomy of glycoprotein g gene in herpes simplex virus type 1 isolates.
AB  - Herpes simplex virus type 1 (HSV-1) encodes 11 envelope glycoproteins, of which
      glycoprotein G-1 (gG-1) induces a type-specific antibody response. Variability of
      the gG-1 gene among wild-type strains may be a factor of importance for a
      reliable serodiagnosis and typing of HSV-1 isolates. Here, we used a gG-1 type
      specific monoclonal antibody (MAb) to screen for mutations in the immunodominant
      region of this protein in 108 clinical HSV-1 isolates. Of these, 42 isolates
      showed no reactivity to the anti-gG-1 MAb. One hundred five strains were further
      examined by DNA sequencing of the middle part of the gG-1 gene, encompassing 106
      amino acids including the immunodominant region and epitope of the anti-gG-1 MAb.
      By phylogenetic comparisons based on the sequence data, we observed two (main)
      genetic variants of the gG-1 gene among the clinical isolates corresponding to
      reactivity or nonreactivity to the anti-gG-1 MAb. Furthermore, four strains
      appeared to be recombinants of the two gG-1 variants. In addition, one strain
      displayed a gG-1-negative phenotype due to a frameshift mutation, in the form of
      insertion of a cytosine nucleotide. When immunoglobulin G reactivity to HSV-1 in
      sera from patients infected with either of the two variants was investigated, no
      significant differences were found between the two groups, either in a type
      common enzyme-linked immunosorbent assay (ELISA) or in a type-specific gG-1
      antigen-based ELISA. Despite the here-documented existence of two variants of the
      gG-1 gene affecting the immunodominant region of the protein, other
      circumstances, such as early phase of infection, might be sought for explaining
      the seronegativity to gG-1 commonly found in a proportion of the HSV-1-infected
      patients.

PMID- 12202561
TI  - Detection and characterization of hepatitis C virus RNA in seminal plasma and
      spermatozoon fractions of semen from patients attempting medically assisted
      conception.
AB  - To investigate the risk of transmission of hepatitis C virus (HCV) via semen in
      assisted reproduction techniques, semen samples from 32 men chronically infected
      with HCV attending a center for assisted procreation were tested for HCV RNA by a
      reverse transcription-PCR protocol by using a modified version of the Cobas
      AMPLICOR HCV assay (version 2.0; Roche Diagnostics). The sensitivity of the test
      was 40 copies/ml. Four of 32 seminal plasma samples (12.5%) were found to be
      positive for the presence of HCV RNA. The median HCV load in blood was
      significantly higher in patients who were found to be positive for the presence
      of HCV RNA in semen than in those who tested negative (P = 0.02). In one man,
      seven consecutive seminal plasma samples tested positive for HCV RNA, as did two
      consecutive motile spermatozoon fractions; the corresponding fractions obtained
      after migration of the spermatozoa remained negative. Despite the absence of the
      proven infectivity of virus in semen samples that test positive for HCV RNA,
      these findings highlight the fact that seminal fluid may exhibit prolonged HCV
      RNA excretion. The usefulness of HCV RNA detection in both seminal plasma and
      spermatozoon fractions before the start of a program of medically assisted
      reproduction in couples in whom the male partner is chronically infected with HCV
      would need to be evaluated prospectively with a larger population of subjects
      exhibiting HCV RNA in their semen.

PMID- 12202562
TI  - Development of a real-time reverse transcriptase PCR assay for type A influenza
      virus and the avian H5 and H7 hemagglutinin subtypes.
AB  - A real-time reverse transcriptase PCR (RRT-PCR) assay based on the avian
      influenza virus matrix gene was developed for the rapid detection of type A
      influenza virus. Additionally, H5 and H7 hemagglutinin subtype-specific probe
      sets were developed based on North American avian influenza virus sequences. The
      RRT-PCR assay utilizes a one-step RT-PCR protocol and fluorogenic hydrolysis type
      probes. The matrix gene RRT-PCR assay has a detection limit of 10 fg or
      approximately 1,000 copies of target RNA and can detect 0.1 50% egg infective
      dose of virus. The H5- and H7-specific probe sets each have a detection limit of
      100 fg of target RNA or approximately 10(3) to 10(4) gene copies. The sensitivity
      and specificity of the real-time PCR assay were directly compared with those of
      the current standard for detection of influenza virus: virus isolation (VI) in
      embryonated chicken eggs and hemagglutinin subtyping by hemagglutination
      inhibition (HI) assay. The comparison was performed with 1,550 tracheal and
      cloacal swabs from various avian species and environmental swabs obtained from
      live-bird markets in New York and New Jersey. Influenza virus-specific RRT-PCR
      results correlated with VI results for 89% of the samples. The remaining samples
      were positive with only one detection method. Overall the sensitivity and
      specificity of the H7- and H5-specific RRT-PCR were similar to those of VI and
      HI.

PMID- 12202563
TI  - Distribution of environmentally regulated genes of Streptococcus suis serotype 2
      among S. suis serotypes and other organisms.
AB  - The occurrence of 36 environmentally regulated genes of Streptococcus suis strain
      10 among all 35 S. suis serotypes was determined by using hybridization with the
      amplified genes as probes. In addition, the distribution of these genes among the
      virulence phenotypes of serotypes 1 and 2 was assessed. Hybridization was also
      performed with various other streptococcal species and nonstreptococcal bacterial
      species which may be present in pigs. Interestingly, probe ivs-25/iri-1, similar
      to agrA and sapR, hybridized only with S. suis serotype 1 and 2 strains with
      virulent phenotypes and is therefore suitable as a diagnostic parameter. Only one
      probe was specific for S. suis. This probe's sequence was identical to the epf
      gene, a putative virulence factor of S. suis. Probe ivs-31 was similar to a
      virulence factor of S. suis, namely, a gene encoding a fibronectin- and
      fibrinogen-binding protein. This probe hybridized only with oral streptococci.
      Nearly half of the probes (45%) hybridized with the oral streptococci (S. oralis,
      S. milleri, S. sanguis, S. gordonii, and S. mitis) and with Streptococcus
      pneumoniae. This indicates a close relationship between S. suis, the oral
      streptococci, and S. pneumoniae with respect to the selected environmentally
      regulated genes. One probe only hybridized with gram-negative species and
      therefore seems to be obtained by S. suis from a gram-negative organism by
      horizontal transfer.

PMID- 12202564
TI  - Effects of various test media on the activities of 21 antimicrobial agents
      against Haemophilus influenzae.
AB  - As considerable variation in the antimicrobial susceptibility of Haemophilus
      influenzae has been reported, the effects of various test media on the
      susceptibility of H. influenzae were studied. MICs were determined by three
      laboratories for 21 antimicrobial agents against a panel of 100 selected
      isolates. Testing was performed using a reference NCCLS frozen broth
      microdilution method with Haemophilus test medium (HTM) broth and dried
      commercial MIC trays rehydrated with the following media: in-house and
      commercially prepared HTM broth, Mueller-Hinton broth with 2% lysed horse blood
      and NAD, IsoSensitest broth with 2% lysed horse blood and NAD, and IsoSensitest
      broth-based HTM. Overall, all results were very reproducible, with the MIC at
      which 50% of the isolates tested are inhibited (MIC(50)), MIC(90), and geometric
      mean MIC being within one doubling dilution by all six methods and at all three
      testing centers for 15 of the 21 agents tested. Interlaboratory differences were
      more marked than intralaboratory differences or differences among media.
      Cefprozil, cefaclor, and trimethoprim-sulfamethoxazole results differed the most,
      while results for ampicillin, amoxicillin-clavulanic acid, cefdinir, cefixime,
      ceftriaxone, and clarithromycin were the most reproducible. However, these
      variations in results caused considerable differences in susceptibility rates for
      agents for which NCCLS susceptible breakpoints were close to the geometric mean
      MIC, particularly for cefaclor and cefprozil. This was much less of a problem
      when pharmacokinetic-pharmacodynamic breakpoints were used. Reproducible
      susceptibility results were obtained for a wide range of agents against H.
      influenzae in three laboratories using a variety of media that support the growth
      of this fastidious species.

PMID- 12202565
TI  - Detection of Trichomonas vaginalis on modified Columbia agar in the routine
      laboratory.
AB  - Broth culture of Trichomonas vaginalis is considered the "gold standard" for the
      diagnosis of trichomoniasis. Two studies were carried out to evaluate modified
      Columbia agar (MCA) for the isolation of T. vaginalis from clinical samples.
      Study I compared isolation on MCA to that on liquid medium with 889 vaginal
      samples. Out of 63 samples positive for T. vaginalis (7.1% of total), MCA
      identified 62 (98.4%) and broth identified 58 (92.1%). In study II,
      trichomoniasis was diagnosed within the scope of a screening program for a total
      of 39,585 men and women by culture on MCA and direct microscopy. Culture on MCA
      detected 199 (98.5%) and Gram staining detected 163 (80.7%) of 202 positive
      specimens. Wet-mount preparations used for symptomatic patients identified 103
      (92.8%) of 111 cases. Culture of T. vaginalis from clinical samples on MCA is
      highly sensitive and reliable, as well as timesaving, and therefore suitable for
      screening of symptomatic and asymptomatic individuals.

PMID- 12202566
TI  - Mycobacterium microti infection (vole tuberculosis) in wild rodent populations.
AB  - Mycobacterium microti (vole tuberculosis) infections in small wild mammals were
      first described more than 60 years ago in several populations in Great Britain.
      Few studies of vole tuberculosis have been undertaken since then, and little is
      known about the relationship between M. microti isolates originating from
      different populations or at different times or of the prevalence of this
      infection in wild rodent populations, despite human cases of M. microti
      infections being increasingly reported. In this study, field voles (Microtus
      agrestis), bank voles (Clethrionomys glareolus), and wood mice (Apodemus
      sylvaticus) were found to be infected, with up to 8% having external tuberculous
      signs, in wild populations in Northumberland and Cheshire, England. Spoligotyping
      applied directly to the clinical material simultaneously detected and typed M.
      microti bacteria in skin lesions, lymph glands, and internal abcesses. IS6110
      restriction fragment length polymorphism typing of cultured bacteria was used to
      compare these isolates with previously isolated strains from both animals and
      humans. This demonstrated that although the current rodent isolates were distinct
      from those isolated from voles in the 1930s in Great Britain, they had a high
      degree of similarity to these strains and were distinct from the M. microti
      isolates from humans, a pig, and a ferret from The Netherlands. Thus, M. microti
      infection seems to be widespread in wild rodent populations, but more studies are
      needed to understand how M. microti might be transmitted from animals to humans
      and to determine better the zoonotic risk posed.

PMID- 12202567
TI  - Simultaneous detection of Anaplasma marginale and a new Ehrlichia species closely
      related to Ehrlichia chaffeensis by sequence analyses of 16S ribosomal DNA in
      Boophilus microplus ticks from Tibet.
AB  - To identify ehrlichial agents in Boophilus microplus ticks, DNA samples of B.
      microplus collected from the Tibet Autonomous Region and Sichuan Province of
      China were screened by a nested PCR. Sixteen of 43 (37%) DNA samples of B.
      microplus from Tibet were positive in nested PCR analysis. All 27 samples from
      Sichuan were negative. The screen identified two ehrlichial agents based on
      different 16S rRNA genes that were found after amplifying and sequencing the 5'
      end fragments of the 16S rRNA genes. One sequence was identical to that of the
      gene of Anaplasma marginale, an etiological agent of animal anaplasmosis. The
      other sequence was most similar to that of the gene of Ehrlichia chaffeensis, an
      etiological agent of human monocytic ehrlichiosis. The sequence of 1,501 bases
      from the novel ehrlichial agent was obtained and showed the greatest levels of
      sequence similarity (97 to 98%) to 16S rRNA gene sequences of the members of the
      E. canis group of the genus EHRLICHIA: Sequence comparison of the 16S rRNA gene
      with the members of the genus Ehrlichia reveals that the novel ehrlichial agent
      detected in B. microplus ticks is a new species of the genus Ehrlichia and is
      most closely related to E. chaffeensis.

PMID- 12202568
TI  - Rapid detection of methicillin resistance in coagulase-negative Staphylococci
      with the VITEK 2 system.
AB  - The aim of the present study was to evaluate the accuracy of the new VITEK 2
      system (bioMerieux, Marcy l' Etoile, France) for the detection of methicillin
      resistance in coagulase-negative staphylococci (CoNS) by using AST-P515 and AST
      P523 test cards. Analyses of the VITEK 2 oxacillin MIC determination evaluated
      according to the actual breakpoint (>/=0.5 micro g/ml) of the National Committee
      for Clinical Laboratory Standards resulted in a high sensitivity of 99.2% but a
      moderate specificity of 80%. The newly included oxacillin resistance (OR) test of
      the VITEK 2 system displayed a high sensitivity and a high specificity of 97.5
      and 98.7%, respectively. Concordance between the results of the mecA PCR and the
      VITEK 2 oxacillin MIC was observed for almost all Staphylococcus epidermidis
      strains, but the reduced specificity was attributable to higher oxacillin MICs
      for mecA-negative non-S. epidermidis strains, especially S. saprophyticus, S.
      lugdunensis, and S. cohnii. Evaluation of alternative oxacillin MIC breakpoints
      of 1, 2, or 4 micro g/ml resulted in improved degrees of specificity of 84, 90.7,
      and 97.3%, respectively. Only minor changes occurred in the corresponding
      sensitivity values, which were 98.4, 97.5, and 97.5%, respectively. Methicillin
      resistance in CoNS was detected after 7 and 8 h in 91.1 and 93.5% of the mecA
      positive strains, respectively, by the VITEK 2 OR test and in 86.3 and 89.5% of
      the mecA-positive strains, respectively, by VITEK 2 oxacillin MIC determination.
      After 7 and 8 h the VITEK 2 OR test classified 59.2 and 78.9% of the mecA
      negative strains, respectively, as susceptible to oxacillin, whereas comparable
      values were obtained 2 h later by VITEK 2 oxacillin MIC determination. The
      results of our study encourage the use of the VITEK 2 system, which proved to be
      a highly reliable and rapid phenotypic method for the detection of methicillin
      resistance in CoNS.

PMID- 12202569
TI  - New variants of Vibrio cholerae O1 biotype El Tor with attributes of the
      classical biotype from hospitalized patients with acute diarrhea in Bangladesh.
AB  - The sixth pandemic of cholera and, presumably, the earlier pandemics were caused
      by the classical biotype of Vibrio cholerae O1, which was progressively replaced
      by the El Tor biotype representing the seventh cholera pandemic. Although the
      classical biotype of V. cholerae O1 is extinct, even in southern Bangladesh, the
      last of the niches where this biotype prevailed, we have identified new varieties
      of V. cholerae O1, of the El Tor biotype with attributes of the classical
      biotype, from hospitalized patients with acute diarrhea in Bangladesh. Twenty
      four strains of V. cholerae O1 isolated between 1991 and 1994 from hospitalized
      patients with acute diarrhea in Matlab, a rural area of Bangladesh, were examined
      for the phenotypic and genotypic traits that distinguish the two biotypes of V.
      cholerae O1. Standard reference strains of V. cholerae O1 belonging to the
      classical and El Tor biotypes were used as controls in all of the tests. The
      phenotypic traits commonly used to distinguish between the El Tor and classical
      biotypes, including polymyxin B sensitivity, chicken cell agglutination, type of
      tcpA and rstR genes, and restriction patterns of conserved rRNA genes
      (ribotypes), differentiated the 24 strains of toxigenic V. cholerae O1 into three
      types designated the Matlab types. Although all of the strains belonged to
      ribotypes that have been previously found among El Tor vibrios, type I strains
      had more traits of the classical biotype while type II and III strains appeared
      to be more like the El Tor biotype but had some classical biotype properties.
      These results suggest that, although the classical and El Tor biotypes have
      different lineages, there are possible naturally occurring genetic hybrids
      between the classical and El Tor biotypes that can cause cholera and thus provide
      new insight into the epidemiology of cholera in Bangladesh. Furthermore, the
      existence of such novel strains may have implications for the development of a
      cholera vaccine.

PMID- 12202570
TI  - Comparative assessment of genotyping methods for epidemiologic study of
      Burkholderia cepacia genomovar III.
AB  - We analyzed a collection of 97 well-characterized Burkholderia cepacia genomovar
      III isolates to evaluate multiple genomic typing systems, including pulsed-field
      gel electrophoresis (PFGE), BOX-PCR fingerprinting and random amplified
      polymorphic DNA (RAPD) typing. The typeability, reproducibility, and
      discriminatory power of these techniques were evaluated, and the results were
      compared to each other and to data obtained in previous studies by using
      multilocus restriction typing (MLRT). All methods showed excellent typeability.
      PFGE with SpeI was more reproducible than RAPD and BOX-PCR fingerprinting. The
      discriminatory power of the methods was variable, with PFGE and RAPD typing
      having a higher index of discrimination than BOX-PCR fingerprinting. In general,
      the results obtained by PFGE, BOX-PCR fingerprinting, and MLRT were in good
      agreement. Our data indicate that different genomic-based methods can be used to
      type B. cepacia genomovar III isolates depending on the situation and the
      epidemiologic question being addressed. PFGE and RAPD fingerprinting are best
      suited to addressing small-scale studies (i.e., local epidemiology), whereas BOX
      PCR fingerprinting is more appropriate for large-scale studies (i.e., global
      epidemiology). In this regard, BOX-PCR fingerprinting can be considered a rapid
      and easy alternative to MLRT.

PMID- 12202571
TI  - Determination of novel Borrelia genospecies in Swedish Ixodes ricinus ticks.
AB  - A total of 301 adult questing Ixodes ricinus ticks were collected at 15 different
      locations along the south and east coasts of Sweden to determine the Borrelia
      genospecies diversity. Thirty-two ticks (11%) were found to be positive by nested
      PCR with Borrelia burgdorferi sensu lato-specific primers. Species determination
      was based on partial sequencing of the 16S rRNA gene and the flagellin gene. Five
      different Borrelia species were found. The nucleotide sequence of the Borrelia
      DNA found in two ticks differed extensively from the nucleotide sequences of the
      Borrelia DNA found in the other ticks, and analysis revealed that they were
      closely related to the relapsing fever borrelia species Borrelia miyamotoi. This
      is the first report of a B. miyamotoi-like borrelia in I. ricinus and in Europe.
      Moreover, the Borrelia DNA of two ticks (6%) clustered within the B. valaisiana
      complex. B. valaisiana has not previously been reported in Sweden. B. afzelii DNA
      was found in 14 ticks (44%), and B. garinii DNA was found in 10 ticks (31%). B.
      burgdorferi sensu stricto DNA was found in four ticks (13%). We conclude that all
      of the known human-pathogenic species (B. garinii, B. afzelii, and B. burgdorferi
      sensu stricto) and B. valaisiana found elsewhere in Europe are also present in
      the Swedish host-seeking tick population and that a B. miyamotoi-like Borrelia
      species seems to be present in I. ricinus ticks in Europe.

PMID- 12202572
TI  - Molecular epidemiology of erythromycin resistance in Streptococcus pneumoniae
      isolates from blood and noninvasive sites.
AB  - Erythromycin-resistant isolates of Streptococcus pneumoniae from blood cultures
      and noninvasive sites were studied over a 3-year period. The prevalence of
      erythromycin resistance was 11.9% (19 of 160) in blood culture isolates but 4.2%
      (60 of 1,435) in noninvasive-site isolates. Sixty-two of the 79 resistant
      isolates were available for study. The M phenotype was responsible for 76% (47 of
      62) of resistance, largely due to a serotype 14 clone, characterized by
      multilocus sequence typing as ST9, which accounted for 79% (37 of 47) of M
      phenotype resistance. The ST9 clone was 4.8 times more common in blood than in
      noninvasive sites. All M phenotype isolates were PCR positive for mef(A), but
      sequencing revealed that the ST9 clone possessed the mef(A) sequence commonly
      associated with Streptococcus pyogenes. All M phenotype isolates with this mef(A)
      sequence also had sequences consistent with the presence of the Tn1207.1 genetic
      element inserted in the celB gene. In contrast, isolates with the mef(E) sequence
      normally associated with S. pneumoniae contained sequences consistent with the
      presence of the mega insertion element. All MLS(B) isolates carried erm(B), and
      two isolates carried both erm(B) and mef(E). Fourteen of the 15 MLS(B) isolates
      were tetracycline resistant and contained tet(M). However, six M phenotype
      isolates of serotypes 19 (two isolates) and 23 (four isolates) were also
      tetracycline resistant and contained tet(M). MICs for isolates with the mef(A)
      sequence were significantly higher than MICs for isolates with the mef(E)
      sequence (P < 0.001). Thus, the ST9 clone of S. pneumoniae is a significant cause
      of invasive pneumococcal disease in northeast Scotland and is the single most
      important contributor to M phenotype erythromycin resistance.

PMID- 12202573
TI  - Rational design of DNA sequence-based strategies for subtyping Listeria
      monocytogenes.
AB  - The ability to differentiate bacteria beyond the species level is essential for
      identifying and tracking infectious disease outbreaks and to improve our
      knowledge of the population genetics, epidemiology, and ecology of bacterial
      pathogens. Commonly used subtyping methods, such as serotyping, phage typing,
      ribotyping, and pulsed-field gel electrophoresis, can yield ambiguous results
      that are difficult to standardize and share among laboratories. DNA sequence
      based subtyping strategies can reduce interpretation ambiguity. We report the
      development of a rational approach for designing sequence-based subtyping
      methods. Listeria monocytogenes was selected as the model organism for testing
      the efficacy of this approach. Two housekeeping genes (recA and prs), one stress
      response gene (sigB), two virulence genes (actA and inlA), and two intergenic
      regions (hly-mpl and plcA-hly) were sequenced for 15 L. monocytogenes isolates.
      Isolates were chosen from a representative collection of more than 1,000 L.
      monocytogenes isolates to reflect the genetic diversity of this species. DNA
      sequences were aligned, and sliding window analyses were performed for each gene
      to define 600-bp-long regions that were (i) most polymorphic (using ProSeq) or
      (ii) most discriminatory (using a new algorithm implemented in WINDOWMIN).
      Complete gene sequences for actA (1,929 bp) and inlA (2,235 bp) provided the
      highest discrimination (identifying 15 and 14 allelic types, respectively).
      WINDOWMIN allowed identification of 600-bp regions within these genes that
      provided similar discriminatory power (yielding 15 and 13 allelic types,
      respectively). The most discriminatory 600-bp fragments identified in the
      housekeeping and stress response genes differentiated the isolates into 8 to 10
      subtypes; intergenic region sequences yielded 8 and 12 allelic types based on 335
      and 242-bp sequences for hly-mpl and plcA-hly, respectively. Regions identified
      as most polymorphic were not necessarily most discriminatory; therefore,
      application of the WINDOWMIN algorithm provided a powerful tool for determining
      the best target regions for DNA sequence-based subtyping. Our specific results
      also show that inclusion of virulence gene target sequences in a DNA sequence
      based subtyping scheme for L. monocytogenes is necessary to achieve maximum
      subtype differentiation.

PMID- 12202574
TI  - Possible connection between a widely disseminated conjugative gentamicin
      resistance (pMG1-like) plasmid and the emergence of vancomycin resistance in
      Enterococcus faecium.
AB  - A total of 640 vancomycin-resistant Enterococcus faecium (VRE) isolates, which
      were obtained between 1994 and 1999 from the Medical School Hospital of the
      University of Michigan, Ann Arbor, were used in this study. Of the 640 strains,
      611 and 29 were VanA and VanB VRE, respectively, based on PCR analysis. Four
      hundred ninety-two (77%) of the strains exhibited resistance to concentrations of
      gentamicin from 64 micro g/ml (MIC) to more than 1,024 micro g/ml (MIC). The
      gentamicin resistance of each of 261 (53%) of the 492 gentamicin-resistant
      strains was transferred to E. faecium at a frequency of about 10(-5) to 10(-6)
      per donor cell in broth mating. More than 90% of vancomycin resistances of the
      261 strains cotransferred with the gentamicin resistances to E. faecium strains
      by filter mating. The conjugative gentamicin resistance plasmids were identified
      and were classified into five types (A through E) with respect to their EcoRI
      restriction profiles. The transfer frequencies of each type of plasmid between E.
      faecium strains or Enterococcus faecalis strains were around 10(-3) to 10(-5) per
      donor cell or around 10(-6) to 10(-7) per donor cell, respectively, in broth
      mating. Type A and type B were the most frequently isolated, at an isolation
      frequency of about 40% per VRE isolate harboring the gentamicin resistance
      conjugative plasmid. The plasmids did not show any homology in Southern
      hybridization with the pheromone-responsive plasmids and broad-host-range
      plasmids pAMbeta1 and pIP501. The EcoRI or NdeI restriction fragments of each
      type of plasmids hybridized to the conjugative gentamicin resistance plasmid pMG1
      (65.1 kb), which was originally isolated from an E. faecium clinical isolate, and
      transfer efficiently in broth mating.

PMID- 12202575
TI  - Detection and quantification of oral treponemes in subgingival plaque by real
      time PCR.
AB  - Oral treponemes have been associated with periodontal diseases. We developed a
      highly sensitive and specific method to detect and quantify cultivable oral
      treponemes (Treponema denticola, Treponema vincentii, and Treponema medium) in 50
      subgingival plaque samples from 13 healthy subjects as well as 37 patients with
      periodontal diseases using real-time PCR assays with specific primers and a
      TaqMan probe for each 16S rRNA sequence. The specificity for each assay was
      examined by using DNA specimens from various treponemal and other bacterial
      species. The TaqMan real-time PCR was able to detect from 10(3) to 10(8) cells of
      the oral treponemes, with correlation coefficients as follows: T. denticola,
      0.984; T. vincentii, 0.991; and T. medium, 0.984. The frequencies of occurrence
      of these three oral treponemes in subgingival plaque samples were as follows: T.
      denticola, 68.0%; T. vincentii, 36.0%; and T. medium, 48.0%. In addition, the
      number of T. denticola, T. vincentii, and T. medium cells in plaque samples
      detected by real-time PCR ranged from 3 to 15,184, 1 to 447, and 1 to 7,301
      cells/pg of plaque DNA, respectively. Increased numbers of T. denticola cells
      were detected in plaque samples from deep periodontal pockets, and T. medium was
      also detected in deep pockets. On the other hand, T. vincentii was mainly found
      in shallow pockets. These results suggest that various oral treponemes are
      associated with the formation of each stage of periodontal disease.

PMID- 12202576
TI  - High prevalence of human papillomavirus (HPV) infections and high frequency of
      multiple HPV genotypes in human immunodeficiency virus-infected women in Brazil.
AB  - A group of 208 human immunodeficiency virus (HIV)-infected women in Brazil were
      studied for the presence of human papillomavirus with the general SPF(10) PCR
      primer set. Virtually all (98%) women were found positive for human
      papillomavirus (HPV) DNA. Genotyping by the reverse hybridization line probe
      assay (HPV-LiPA) revealed a high prevalence of multiple genotypes (78.9% of the
      cases), with an average of 3.1 genotypes per patient (range, 1 to 10 genotypes).
      HPV 6 was the most prevalent genotype and was observed in 80 (39.2%) patients,
      followed by types 51 (31.9%), 11 (26.0%), 18 (24.0%), and 16 (22.5%). Of the
      genotypes detected, 40.9% were low-risk genotypes. Twenty-two (10.5%) patients
      showed normal (Pap I) cytology, 149 (71.6%) patients had inflammation (Pap II),
      and 28 patients (13.4%) had a Pap III score. The prevalence of high-risk
      genotypes increased with the cytological classification. There were no
      significant associations between the number of HPV genotypes detected and the
      cytological classification, HIV viral load, and CD4 count in these patients. In
      conclusion, the highly sensitive SPF(10) LiPA system shows that a very high
      proportion of HIV-infected women in Brazil are infected with HPV and often carry
      multiple HPV genotypes.

PMID- 12202577
TI  - Leptotrichia amnionii sp. nov., a novel bacterium isolated from the amniotic
      fluid of a woman after intrauterine fetal demise.
AB  - A novel bacterium was isolated and characterized from the amniotic fluid of a
      woman who experienced intrauterine fetal demise in the second trimester of
      pregnancy. The bacterium was a slow-growing, gram-negative anaerobic
      coccobacillus belonging to the genus LEPTOTRICHIA: Unlike Leptotrichia
      sanguinegens, the isolate did not grow in chopped-meat glucose broth or on sheep
      blood agar upon subculturing. The isolate was characterized by sequencing and
      analyzing its 16S rRNA gene. The 1,493-bp 16S ribosomal DNA sequence had only 96%
      homology with L. sanguinegens. Several phylogenetic analyses indicated that L.
      amnionii is a distinct species and most closely related to L. sanguiegens.

PMID- 12202578
TI  - Fast, noninvasive method for molecular detection and differentiation of
      Malassezia yeast species on human skin and application of the method to dandruff
      microbiology.
AB  - Malassezia fungi have been the suspected cause of dandruff for more than a
      century. Previously referred to as Pityrosporum ovale, Pityrosporum orbiculare,
      or Malassezia, these fungi are now known to consist of at least seven Malassezia
      species. Each species has a specific ecological niche, as well as specific
      biochemical and genetic characteristics. Malassezia yeasts have fastidious
      culture conditions and exceedingly different growth rates. Therefore, the results
      of surveys of Malassezia based on culture methods can be difficult to interpret.
      We developed a molecular technique, terminal fragment length polymorphism
      analysis, to more accurately survey the ecology of Malassezia yeasts without bias
      from culture. This technique involves fluorescent nested PCR of the intergenic
      transcribed spacer (ITS) ITS I and ITS II region ribosomal gene clusters. All
      known Malassezia species can be differentiated by unique ITS fragment lengths. We
      have used this technique to directly analyze scalp samples from subjects enrolled
      in a demographic scalp health study. Results for subjects assigned composite
      adherent scalp flaking scores (ASFS) <10 were compared to those for subjects
      assigned composite ASFS >24. Malassezia restricta and M. globosa were found to be
      the predominant Malassezia species present in both groups. Importantly, we found
      no evidence of M. furfur in either group, indicating that M. furfur can be
      eliminated as the causal organism for dandruff. Both groups also showed the
      presence of non-Malassezia fungi. This method, particularly when it is used in
      combination with existing fungal ITS databases, is expected to be useful in the
      diagnosis of multiple other fungal infections.

PMID- 12202579
TI  - Detection of Rickettsia prowazekii in body lice and their feces by using
      monoclonal antibodies.
AB  - In order to identify Rickettsia prowazekii in lice, we developed a panel of 29
      representative monoclonal antibodies selected from 187 positive hybridomas made
      by fusing splenocytes of immunized mice with SP2/0-Ag14 myeloma cells.
      Immunoblotting revealed that 15 monoclonal antibodies reacted with the
      lipopolysaccharide-like (LPS-L) antigen and 14 reacted with the epitopes of a 120
      kDa protein. Only typhus group rickettsiae reacted with the monoclonal antibodies
      against LPS-L. R. felis, a recently identified rickettsial species, did not react
      with these monoclonal antibodies, confirming that it is not antigenically related
      to the typhus group. Monoclonal antibodies against the 120-kDa protein were
      highly specific for R. prowazekii. We successfully applied a selected monoclonal
      antibody against the 120-kDa protein to detect by immunofluorescence assay R.
      prowazekii in smears from 56 wild and laboratory lice, as well as in 10 samples
      of louse feces infected or not infected with the organism. We have developed a
      simple, practical, and specific diagnostic assay for clinical specimens and large
      scale epidemiological surveys with a sensitivity of 91%. These monoclonal
      antibodies could be added to the rickettsial diagnostic panel and be used to
      differentiate R. prowazekii from other rickettsial species.

PMID- 12202580
TI  - Rapid-cycle PCR and fluorimetry for detection of mycobacteria.
AB  - In this study we used LightCycler PCR amplification and product detection by
      fluorescence resonance energy transfer probes to identify mycobacteria and
      differentiate between Mycobacterium tuberculosis complex, Mycobacterium avium,
      and other nontuberculous mycobacteria. Targeting the 16S rRNA gene, three
      different probes specific for mycobacteria, M. tuberculosis complex, and M. avium
      were constructed. As few as five genome copies of target nucleic acid were
      detected by the probes, illustrating the high sensitivity of the system. All 33
      mycobacterial species tested but none of the closely related actinomycetes and
      other bacteria produced a specific fluorescence signal. A specificity of 100% was
      also demonstrated for the M. tuberculosis complex-specific probe and the M. avium
      specific probe. Within 45 min, the LightCycler method correctly detected
      mycobacteria and specifically identified M. tuberculosis complex and M. avium
      without any post-PCR sample manipulation. In view of future clinical studies, we
      also constructed and tested an internal control which could be used to assure
      successful amplification and detection of mycobacteria. Monitoring of PCR
      inhibition will be essential for evaluation of this system for direct detection
      of mycobacteria in clinical specimens. Finally, we tested our system on sputum
      seeded with mycobacteria and were able to detect as few as 10 organisms. At
      present, this system is the fastest available method for identification and
      differentiation of mycobacteria from culture-positive specimens and offers an
      excellent alternative to previously established nucleic acid amplification-based
      techniques for the diagnostic mycobacterial laboratory.

PMID- 12202581
TI  - Clinical and epidemiological correlates of genotypes within the Mycobacterium
      avium complex defined by restriction and sequence analysis of hsp65.
AB  - Species identification of isolates of the Mycobacterium avium complex (MAC)
      remains a difficult task. Although M. avium and Mycobacterium intracellulare can
      be identified with expensive, commercially available probes, many MAC isolates
      remain unresolved, including those representing Mycobacterium lentiflavum as well
      as other potentially undefined species. PCR restriction analysis (PRA) of the
      hsp65 gene has been proposed as a rapid and inexpensive approach. We applied PRA
      to 278 MAC isolates, including 126 from blood of human immunodeficiency virus
      (HIV)-infected patients, 59 from sputum of HIV-negative patients with chronic
      obstructive pulmonary disease, 88 from environmental sources, and 5 pulmonary
      isolates from a different study. A total of 15 different PRA patterns were
      observed. For 27 representative isolates, a 441-bp fragment of the hsp65 gene was
      sequenced; based on 54 polymorphic sites, 18 different alleles were defined,
      including 12 alleles not previously reported. Species and phylogenetic
      relationships were more accurately defined by sequencing than by PRA or
      commercial probe. The distribution of PRA types and, by implication, phylogenetic
      lineages among blood isolates was significantly different from that for pulmonary
      and environmental isolates, suggesting that particular lineages have appreciably
      greater virulence and invasive potential.

PMID- 12202582
TI  - Malignant catarrhal fever-like disease in Barbary red deer (Cervus elaphus
      barbarus) naturally infected with a virus resembling alcelaphine herpesvirus 2.
AB  - Eight Barbary red deer (Cervus elaphus barbarus) developed clinical signs
      suggestive of malignant catarrhal fever (MCF) over a 28-day period. These animals
      were housed outdoors with four other species of ruminants. Affected red deer had
      lethargy, ocular signs, and nasal discharge and were euthanatized within 48 h.
      Lesions included ulcers of the muzzle, lips, and oral cavity associated with
      infiltrates of neutrophils and lymphocytes. Serologically, six of seven red deer
      tested during the outbreak were positive by competitive enzyme-linked
      immunosorbent assay for antibodies to a shared MCF virus antigen. PCR using
      oligonucleotide primers designed for a conserved protein of alcelaphine
      herpesviruses 1 (AlHV-1) and 2 (AlHV-2) and for conserved regions of a
      herpesvirus DNA polymerase gene was positive for tissues from all eight
      clinically affected animals and negative for eight out of eight red deer without
      clinical signs of MCF. DNA sequencing of PCR amplicons from the diseased red deer
      indicated that they were infected with a novel herpesvirus closely related to
      AlHV-2; immunohistochemistry using polyclonal anti-AlHV-2 serum and in situ
      hybridization demonstrated the presence of virus within salivary glands adjacent
      to oral lesions of affected animals. A survey of other ruminants near the
      outbreak subsequently showed that normal Jackson's hartebeest (Alcelaphus
      buselaphus jacksoni) that were cohoused with the diseased red deer were infected
      with the same virus and were shedding the virus in nasal excretions. These
      findings suggest that a herpesvirus closely related to AlHV-2 caused the MCF-like
      disease epizootic in Barbary red deer and that the virus may have originated from
      Jackson's hartebeest.

PMID- 12202583
TI  - Practical approach for typing strains of Leishmania infantum by microsatellite
      analysis.
AB  - Currently the universally accepted standard procedure for characterizing and
      identifying strains of Leishmania is isoenzyme analysis. However, in the
      Mediterranean area, despite their very wide geographical distribution, most
      Leishmania infantum strains belong to zymodeme MON-1. In order to increase our
      understanding of polymorphism in strains of L. infantum, we developed PCR assays
      amplifying 10 microsatellites and sequenced PCR products. The discriminative
      power of microsatellite analysis was tested by using a panel of 50 L. infantum
      strains collected from patients and dogs from Spain, France, and Israel,
      including 32 strains belonging to zymodeme MON-1, 8 strains belonging to
      zymodemes MON-24, MON-29, MON-33, MON-34, or MON-80, and 10 untyped strains. Five
      of the microsatellites were polymorphic, revealing 22 genotypes, whereas the five
      remaining microsatellites were not variable. In particular, MON-1 strains could
      be separated into 13 different closely related genotypes. MON-33 and MON-34
      strains also gave two additional genotypes closely related to MON-1, while MON
      29, MON-24, and MON 80 strains exhibited more divergent genotypes. Among the foci
      examined, the Catalonian focus displayed a high polymorphism, probably reflecting
      isoenzyme polymorphism, while the Israeli focus exhibited a low polymorphism that
      could be consistent with the recent reemergence and rapid spread of canine
      leishmaniasis in northern and central Israel. The strains originating from the
      south of France and the Madrid, Spain, area displayed significant microsatellite
      polymorphism even though they were monomorphic by isoenzyme analysis. In
      conclusion, microsatellite polymorphism exhibits a high discriminative power and
      appears to be suitable for characterization of closely related strains of L.
      infantum in epidemiological studies.

PMID- 12202584
TI  - Mycobacterium africanum subtype II is associated with two distinct genotypes and
      is a major cause of human tuberculosis in Kampala, Uganda.
AB  - The population structure of 234 Mycobacterium tuberculosis complex strains
      obtained during 1995 and 1997 from tuberculosis patients living in Kampala,
      Uganda (East Africa), was analyzed by routine laboratory procedures,
      spoligotyping, and IS6110 restriction fragment length polymorphism (RFLP) typing.
      According to biochemical test results, 157 isolates (67%) were classified as M.
      africanum subtype II (resistant to thiophen-2-carboxylic acid hydrazide), 76
      isolates (32%) were classified as M. tuberculosis, and 1 isolate was classified
      as classical M. bovis. Spoligotyping did not lead to clear differentiation of M.
      tuberculosis and M. africanum, but all M. africanum subtype II isolates lacked
      spacers 33 to 36, differentiating them from M. africanum subtype I. Moreover,
      spoligotyping was not sufficient for differentiation of isolates on the strain
      level, since 193 (82%) were grouped into clusters. In contrast, in the IS6110
      based dendrogram, M. africanum strains were clustered into two closely related
      strain families (Uganda I and II) and clearly separated from the M. tuberculosis
      isolates. A further characteristic of both M. africanum subtype II families was
      the absence of spoligotype spacer 40. All strains of family I also lacked spacer
      43. The clustering rate obtained by the combination of spoligotyping and RFLP
      IS6110 analysis was similar for M. africanum and M. tuberculosis, as 46% and 49%
      of the respective isolates were grouped into clusters. The results presented
      demonstrate that M. africanum subtype II isolates from Kampala, Uganda, belong to
      two closely related genotypes, which may represent unique phylogenetic branches
      within the M. tuberculosis complex. We conclude that M. africanum subtype II is
      the main cause of human tuberculosis in Kampala, Uganda.

PMID- 12202585
TI  - Fluorescent amplified fragment length polymorphism analysis of Salmonella
      enterica serovar typhimurium reveals phage-type- specific markers and potential
      for microarray typing.
AB  - Fluorescent amplified fragment length polymorphism (AFLP) was applied to 46
      Salmonella enterica serovar Typhimurium isolates of Australian origin comprising
      nine phage types, by using the restriction enzymes MseI and EcoRI and all 16
      possible MseI +1-EcoRI +1 primer pair combinations. AFLP in the present study
      showed a very good discrimination power with a Simpson index of diversity of
      0.98, and 35 different AFLP patterns were observed in the 46 isolates. AFLP
      grouped most serovar Typhimurium isolates by phage type and enabled
      differentiation of phage types. Furthermore, 84 phage-type-specific polymorphic
      AFLP fragments, for which presence or absence correlated with phage type
      (including 25 with one exception to phage type specificity) were observed in the
      46 strains studied. Eighteen phage-type-specific AFLP fragments were cloned and
      sequenced. Fifteen are of known genes or have a homologue in the databases. Three
      sequences are plasmid related, eight are phage related, and four relate to
      chromosomal genes. Twelve of the 18 fragments are polymorphic because the DNA is
      present or absent as indicated by Southern hybridization, and we see good
      potential to use sequences of these fragments as the basis for multiplex PCR and
      development of a microarray-based molecular phage-typing method for serovar
      Typhimurium.

PMID- 12202586
TI  - Comparison of lysis filtration and an automated blood culture system (BACTEC) for
      detection, quantification, and identification of odontogenic bacteremia in
      children.
AB  - Lysis filtration (LyF) was compared with BACTEC PAEDS PLUS in estimating the
      prevalence of, and sensitivity for, detection of odontogenic bacteremia. Both
      real bacteremia and simulated bacteremia (seeded blood or saline samples) were
      assessed to determine the validity of LyF in estimating bacteremia. The simulated
      bacteremia was also used to assess the reliability of LyF to estimate intensity
      of bacteremia in CFU per milliliter of blood. Reference organisms were used to
      assess the abilities of LyF and BACTEC to isolate known oral streptococci. There
      was no difference in the number of CFU per milliliter of seeded saline, seeded
      blood, and drop cultures of the organisms plated directly onto agar. Blood cell
      volume had a negligible effect on the yield of organisms for simulated
      bacteremia. When LyF and BACTEC were compared, the time to detection of
      bacteremia was always significantly shorter for BACTEC. For aerobic cultures,
      these times were 43.7 and 9.6 h, respectively (P < 0.01). For anaerobic cultures,
      these times were 45.1 and 9.9 h, respectively (P < 0.01). These differences
      occurred as well for bacteremia following the extraction of a single tooth, with
      LyF and BACTEC aerobic cultures taking 78 and 30.5 h, respectively (P < 0.0001).
      For anaerobic cultures, the times were 90.8 and 45 h, respectively (P < 0.0004).
      A preextraction bacteremia was detected on 2.1% of occasions with BACTEC compared
      to 31% of occasions with LyF (P < 0.05) The use of LyF was an effective and
      reliable means of estimating the intensity of pre- and postextraction bacteremia.
      The values were 3.6 and 5.9 CFU/ml, respectively (P < 0.4729), and the difference
      was not statistically significant. In summary, BACTEC is quicker than LyF, but
      less sensitive. LyF provides additional important information in estimating the
      intensity of bacteremia.

PMID- 12202587
TI  - Biological and biochemical characterization of sheep scrapie in Japan.
AB  - Due to the apparent absence of an agent-specific nucleic acid genome, scrapie
      strains cannot be classified by genome characterization, which is commonly used
      for the classification of many viruses. However, scrapie strains can be
      distinguished to some extent by biological properties such as transmissibility to
      experimental animals and distribution of neuropathological lesions and by
      biochemical properties such as the molecular mass and relative protease
      resistance of the disease-specific isoform of prion protein (PrP(Sc)). In order
      to preliminarily characterize the scrapie strains that are prevalent in Japan, we
      analyzed the transmissibility of sheep scrapie isolates to mice and the relative
      proteinase K (PK) resistance of the corresponding PrP(Sc). The results indicate
      that Japanese scrapie strains can be divided into at least three groups based on
      biological and biochemical properties. The first group includes isolates which
      cause disease in mice with an incubation period of approximately 400 days and
      possess PrP(Sc) with relatively high PK resistance. Isolates of the second group
      contain PrP(Sc) that is highly resistant to PK digestion but transmit poorly to
      mice. The final group consists of isolates that cause disease in mice with an
      incubation period of less than 300 days and are associated with PrP(Sc) with
      reduced PK resistance. Sheep scrapie has occurred sporadically in Japan
      since1982, with only approximately 60 officially reported cases so far. However,
      the diversity of scrapie strains in the field suggested by our data raises the
      concern that a scrapie strain similar to the parental agent of bovine spongiform
      encephalopathy could exist or emerge in Japan. Thus, continuous surveillance for
      scrapie will be required to prevent the further spread of scrapie, not only among
      the sheep population but also to other species, and to eliminate any potential
      risk of sheep scrapie to public health.

PMID- 12202588
TI  - Actinomyces cardiffensis sp. nov. from human clinical sources.
AB  - Eight strains of a previously undescribed catalase-negative Actinomyces-like
      bacterium were recovered from human clinical specimens. The morphological and
      biochemical characteristics of the isolates were consistent with their assignment
      to the genus Actinomyces, but they did not appear to correspond to any recognized
      species. 16S rRNA gene sequence analysis showed the organisms represent a
      hitherto unknown species within the genus Actinomyces related to, albeit distinct
      from, a group of species which includes Actinomyces turicensis and close
      relatives. Based on biochemical and molecular genetic evidence, it is proposed
      that the unknown isolates from human clinical sources be classified as a new
      species, Actinomyces cardiffensis sp. nov. The type strain of Actinomyces
      cardiffensis is CCUG 44997(T).

PMID- 12202589
TI  - Serodiagnosis of imported schistosomiasis by a combination of a commercial
      indirect hemagglutination test with Schistosoma mansoni adult worm antigens and
      an enzyme-linked immunosorbent assay with S. mansoni egg antigens.
AB  - A commercial indirect hemagglutination (IHA) test using erythrocytes coated with
      Schistosoma mansoni adult worm antigens (WA) and an enzyme-linked immunosorbent
      assay (ELISA) with S. mansoni egg antigens (SEA) were assessed for their use in
      serodiagnosis of imported schistosomiasis (hereafter these tests are designated
      WA/IHA and SEA/ELISA, respectively). The sensitivity of the tests was evaluated
      with sera from 75 patients with proven S. mansoni infection, 25 with proven S.
      haematobium infection, and 10 with clinical Katayama fever. The specificity was
      assessed with sera from 283 patients with various parasitic, bacterial, viral,
      and fungal infections and sera containing autoimmune antibodies. Sensitivities of
      the WA/IHA with a cutoff titer of 1:160 (WA/IHA(160)) in detecting S. mansoni, S.
      haematobium, S. mansoni and S. haematobium combined, and clinical Katayama fever
      were 88.0, 80.0, 86.0, and 70.0%, respectively, with a specificity of 98.9%. The
      WA/IHA with a cutoff of 1:80 (WA/IHA(80)) showed sensitivities of 94.7, 92.0,
      94.0, and 90.0%, respectively, with a specificity of 94.7%. The comparable values
      of SEA/ELISA were 93.3, 92.0, 93.0, and 50.0%, respectively, with a specificity
      of 98.2%. Combined use of ELISA and WA/IHA(80) gave sensitivities of 100% for S.
      mansoni, S. haematobium, and S. mansoni and S. haematobium combined and 90% for
      Katayama fever. The specificity of this combination in detecting schistosomiasis
      was 92.9%. Combination of SEA/ELISA with WA/IHA(160) gave sensitivities of 98.7,
      96.0, 98.0, and 80% with a specificity of 97.2%. Our findings suggest that WA/IHA
      and SEA/ELISA are each sensitive and specific serological tests that are easy to
      use for the diagnosis of imported schistosomiasis. The combined use of these two
      tests enabled the serological diagnosis of schistosomiasis to be achieved with
      very high degrees of both sensitivity and specificity.

PMID- 12202590
TI  - Taxonomic subgroups of Pasteurella multocida correlate with clinical
      presentation.
AB  - Pasteurella multocida is a small nonmotile gram-negative coccobacillus that is
      found in the nasopharynx and gastrointestinal tract of many wild and domesticated
      animals. In humans it most commonly causes cellulitis and localized superficial
      skin abscesses following an animal bite or scratch. The respiratory tract is the
      second most common site of infection for PASTEURELLA: Of the more than 17 species
      of Pasteurella known, Pasteurella multocida subsp. multocida and Pasteurella
      multocida subsp. septica are among the most common pathogens in humans. With the
      use of molecular techniques, distinction between different subspecies of P.
      multocida can be made more easily and accurately. We used the sequence of the 16S
      ribosomal DNA (rDNA) and repetitive extragenic palindromic sequence-PCR (REP-PCR)
      to characterize 20 strains (14 of P. multocida subsp. multocida and 6 of P.
      multocida subsp. septica; the 16S rDNA is identical for P. multocida subsp.
      multocida and Pasteurella multocida subsp. gallicida but differs from that of P.
      multocida subsp. septica) isolated from various anatomic sites. We found
      excellent correlation between the 16S rDNA sequence (a marker for a small
      conserved region of the genome), REP-PCR (a marker for a large portion of the
      genome), and biochemical tests (trehalose and sorbitol). We also found a
      correlation between the clinical presentation and the taxonomic group, with P.
      multocida subsp. septica more often associated with wounds than with respiratory
      infections (67 versus 17%, respectively) (P < 0.05, Z test) and P. multocida
      subsp. multocida more often associated with respiratory infections than with
      wounds (71 versus 14%, respectively) (P < 0.05, Z test).

PMID- 12202591
TI  - Genotypic diversity of clinical Actinomyces species: phenotype, source, and
      disease correlation among genospecies.
AB  - We determined the frequency distribution of Actinomyces spp. recovered in a
      routine clinical laboratory and investigated the clinical significance of
      accurate identification to the species level. We identified 92 clinical strains
      of Actinomyces, including 13 strains in the related Arcanobacterium-Actinobaculum
      taxon, by 16S rRNA gene sequence analysis and recorded their biotypes, sources,
      and disease associations. The clinical isolates clustered into 21 genogroups.
      Twelve genogroups (74 strains) correlated with a known species, and nine
      genogroups (17 strains) did not. The individual species had source and disease
      correlates. Actinomyces turicensis was the most frequently isolated species and
      was associated with genitourinary tract specimens, often with other organisms and
      rarely with inflammatory cells. Actinomyces radingae was most often associated
      with serious, chronic soft tissue abscesses of the breast, chest, and back.
      Actinomyces europaeus was associated with skin abscesses of the neck and genital
      areas. Actinomyces lingnae, Actinomyces gravenitzii, Actinomyces odontolyticus,
      and Actinomyces meyeri were isolated from respiratory specimens, while A.
      odontolyticus-like strains were isolated from diverse sources. Several of the
      species were commonly coisolated with a particular bacterium: Actinomyces
      israelii was the only Actinomyces spp. coisolated with Actinobacillus
      (Haemophilus) actinomycetemcomitans; Actinomyces meyeri was coisolated with
      Peptostreptococcus micros and was the only species other than A. israelii
      associated with sulfur granules in histological specimens. Most genogroups had
      consistent biotypes (as determined with the RapID ANA II system); however,
      strains were misidentified, and many codes were not in the database. One biotype
      was common to several genogroups, with all of these isolates being identified as
      A. meyeri. Despite the recent description of new Actinomyces spp., 19% of the
      isolates recovered in our routine laboratory belonged to novel genospecies. One
      novel group with three strains, Actinomyces houstonensis sp. nov., was
      phenotypically similar to A. meyeri and A. turicensis but was genotypically
      closest to Actinomyces neuii. A. houstonensis sp. nov. was associated with
      abscesses. Our data documented consistent site and disease associations for 21
      genogroups of Actinomyces spp. that provide greater insights into appropriate
      treatments. However, we also demonstrated a complexity within the Actinomyces
      genus that compromises the biochemical identification of Actinomyces that can be
      performed in most clinical laboratories. It is our hope that this large group of
      well-defined strains will be used to find a simple and accurate biochemical test
      for differentiation of the species in routine laboratories.

PMID- 12202592
TI  - Quantitative multiprobe PCR assay for simultaneous detection and identification
      to species level of bacterial pathogens.
AB  - We describe a novel adaptation of the TaqMan PCR assay which potentially allows
      for highly sensitive detection of any eubacterial species with simultaneous
      species identification. Our system relies on a unique multiprobe design in which
      a single set of highly conserved sequences encoded by the 16S rRNA gene serves as
      the primer pair and is used in combination with both an internal highly conserved
      sequence, the universal probe, and an internal variable region, the species
      specific probe. A pre-PCR ultrafiltration step effectively decontaminates or
      removes background DNA. The TaqMan system described reliabAly detected 14 common
      bacterial species with a detection limit of 50 fg. Further, highly sensitive and
      specific pathogen detection was demonstrated with a prototype species-specific
      probe designed to detect Staphylococcus aureus. This assay has broad potential in
      the clinical arena for rapid and specific diagnosis of infectious diseases.

PMID- 12202593
TI  - Characterization of hepatitis C virus quasispecies by matrix-assisted laser
      desorption ionization-time of flight (mass spectrometry) mutation detection.
AB  - Hepatitis C virus (HCV), the causative agent of hepatitis C, frequently causes
      chronic infection. The mechanisms of viral persistence continue to be the object
      of investigation. An important aspect of HCV chronic infection is the
      quasispecies nature of the viral population, which has been particularly well
      documented in the hypervariable region 1 of the E2 glycoprotein. Recent studies
      show that characterization of the quasispecies diversity at the amino acid level
      can help to predict the outcome of HCV infection. Currently the accurate
      characterization of HCV quasispecies requires the cloning of PCR products,
      followed by the sequencing of many clones. In this study we present a new method
      to characterize HCV quasispecies, based on in vitro translation of the amplicons,
      followed by mass spectrometry analysis of the resulting peptide mix. The assay
      was used on reference HCV samples and on clinical samples. In principle, this
      method could be applied to other chronic viral infections in which quasispecies
      play a role.

PMID- 12202594
TI  - Molecular typing of papillomatous digital dermatitis-associated Treponema
      isolates based on analysis of 16S-23S ribosomal DNA intergenic spacer regions.
AB  - Papillomatous digital dermatitis (PDD), an emerging infectious disease of cattle,
      is characterized by painful, ulcerative foot lesions. The detection of high
      numbers of invasive spirochetes in PDD lesions suggests an important role for
      these organisms in the pathogenesis of PDD. PDD-associated spirochetes have
      phenotypic characteristics consistent with members of the genus TREPONEMA:
      Partial 16S ribosomal DNA (rDNA) sequence analysis of clonal isolates from
      California cattle showed that they comprise three phylotypes which cluster
      closely with human-associated Treponema spp. of the oral cavity (T. denticola and
      T. medium/T. vincentii) or genital area (T. phagedenis). The goal of our study
      was to apply 16S-23S rDNA intergenic spacer region (ISR) sequence analysis to the
      molecular typing of U.S. PDD-associated Treponema isolates. This methodology has
      potentially greater discriminatory power for differentiation of closely related
      bacteria than 16S rDNA analysis. We PCR amplified, cloned, and sequenced the ISRs
      from six California PDD-associated Treponema isolates and, for comparative
      purposes, one strain each of T. denticola, T. medium, T. vincentii, and T.
      phagedenis. Two ISRs that varied in length and composition were present in all
      the PDD-associated Treponema isolates and in T. denticola, T. medium, and T.
      phagedenis. ISR1 contained a tRNA(Ala) gene, while ISR2 contained a tRNA(Ile)
      gene. Only a single ISR (ISR1) was identified in T. vincentii. Comparative
      analyses of the ISR1 and ISR2 sequences indicated that the California PDD
      associated Treponema isolates comprised three phylotypes, in agreement with the
      results of 16S rDNA analysis. PCR amplification of the 16S-tRNA(Ile) region of
      ISR2 permitted rapid phylotyping of California and Iowa PDD-associated Treponema
      isolates based on product length polymorphisms.

PMID- 12202595
TI  - Molecular analysis of the pathogenicity locus and polymorphism in the putative
      negative regulator of toxin production (TcdC) among Clostridium difficile
      clinical isolates.
AB  - The pathogenicity locus (PaLoc) of Clostridium difficile contains toxin A and B
      genes and three accessory genes, including tcdD and tcdC, which are supposed to
      code for the positive and negative regulators of toxin expression, respectively.
      Different studies have described variations in C. difficile toxin A and B genes,
      but little is known about C. difficile variants for the accessory genes. The
      PaLoc of several C. difficile clinical isolates was investigated by three
      different PCR methods with the aim to identify variant strains. Of the
      toxinogenic C. difficile strains examined, 25% showed variations. No correlation
      between C. difficile variant strains and key patient groups was found.
      Interestingly, all of these strains showed a variant tcdC gene. Three different
      tcdC alleles were identified, and one of these had a nonsense mutation which
      reduced the TcdC protein from 232 to 61 amino acids. It is possible that
      different TcdC variants affect toxin production differently, a hypothesis with
      important implications for the pathogenic potential of variant C. difficile
      strains.

PMID- 12202596
TI  - Labor and cost requirements of two commercial assays for qualitative molecular
      detection of hepatitis C virus.
AB  - The Bayer transcription-mediated amplification (TMA) and the Roche PCR Amplicor
      version 2.0 molecular assays for the qualitative detection of hepatitis C virus
      were compared for cost, hands-on time, assay duration, and complexity. The TMA
      assay compares well to PCR and may be especially useful for laboratories with
      large numbers of test requests.

PMID- 12202597
TI  - Evaluation of genotype and LiPA MYCOBACTERIA assays for identification of Finnish
      mycobacterial isolates.
AB  - Two DNA strip assays, INNO-LiPA MYCOBACTERIA and GenoType Mykobakterien, were
      evaluated for identification of 81 Finnish mycobacterial isolates. The LiPA assay
      correctly identified 89.4% of the 66 isolates studied, and the GenoType assay
      identified 95.1% of 81 isolates. The GenoType assay had a wider selection of
      species and less stringent temperature requirements.

PMID- 12202598
TI  - Are three sputum acid-fast bacillus smears necessary for discontinuing
      tuberculosis isolation?
AB  - To evaluate the efficacy of three sputum acid-fast bacillus (AFB) smears to rule
      out pulmonary tuberculosis, sputum AFB smear and culture results were analyzed at
      two university-affiliated teaching hospitals. The negative predictive value of
      the smear increased by only 0.2% on days 2 and 3 each, indicating that in low
      prevalence populations, there is limited value in requiring three negative sputum
      AFB smears before discontinuing tuberculosis isolation.

PMID- 12202599
TI  - Direct PCR detection of Burkholderia cepacia complex and identification of its
      genomovars by using sputum as source of DNA.
AB  - We developed a nested PCR assay that detects the recA gene of the Burkholderia
      cepacia complex in sputum. The product of the first PCR round is also used to
      identify the genomovar of the pathogen. The protocol achieves high sensitivity
      and specificity with simple interpretation of genomovar status.

PMID- 12202600
TI  - Increasing incidence of candidemia: results from a 20-year nationwide study in
      Iceland.
AB  - A nationwide study on candidemia was conducted in Iceland from 1980 to 1999. The
      annual incidence increased from 1.4 cases/100,000 inhabitants/year between 1980
      and 1984 to 4.9 cases/100,000 inhabitants/year between 1995 and 1999 (P <
      0.0001). Candidemia episodes at university hospitals increased from 0.15/1,000
      admissions to 0.55/1,000 admissions (P < 0.0001). Candida albicans was the
      predominant species responsible (64.4%). The national import of fluconazole
      increased approximately fourfold during the second half of the study, but
      increased resistance to this agent was not observed.

PMID- 12202601
TI  - Rate of hepatitis B virus infection in pregnant women determined by a monoclonal
      hepatitis B surface antigen immunoassay.
AB  - The rate of HBsAg in 6,976 B-human chorionic gonadotropin (B-hCG)-positive
      specimens, as determined by the Auszyme Monoclonal assay (Abbott Laboratories,
      Abbott Park, Ill.), was 0.56% (39 of 6,986 repeatedly reactive [RR] and confirmed
      positive specimens). All RR and confirmed specimens were hepatitis B virus
      positive by at least one additional test, yielding an assay specificity of
      99.96%. The findings argue against unique attributes in the pregnant population
      that might produce inaccurate assay results.

PMID- 12202602
TI  - Technical improvement to prevent DNA degradation of enteric pathogens in pulsed
      field gel electrophoresis.
AB  - This study used a modified pulsed-field gel electrophoresis (PFGE) method with
      HEPES as a running buffer to prevent electrophoresis-related DNA degradation of
      nine Salmonella enterica subsp. enterica serovar Ohio, seven Salmonella serovar
      Newport, and two enterohemorrhagic Escherichia coli (non-O157) strains. All
      strains yielded identifiable bands with this method in contrast to a commonly
      applied PFGE method using Tris buffer.

PMID- 12202603
TI  - Early detection of negative BACTEC MGIT 960 cultures by PCR-reverse cross-blot
      hybridization assay.
AB  - We evaluated the efficacy of a PCR-reverse cross-blot hybridization assay, a test
      which permits identification of mycobacteria by means of species-specific probes
      and a Mycobacterium-specific probe, for early detection of negative BACTEC MGIT
      960 mycobacterial cultures. Aliquots of 549 cultures were collected 7 days after
      the culture media were inoculated with various clinical specimens and tested with
      the molecular assay. PCR results were compared to those obtained at the end times
      with the BACTEC MGIT 960 system. Of the 549 specimens analyzed, 484 were found to
      be negative and 64 were found positive by both methods; one specimen, found to be
      positive by the BACTEC MGIT 960 system, was identified as negative by the
      molecular assay. In view of its high negative predictive value (99.8%), the PCR
      reverse cross-blot hybridization assay appears to be a valid tool for early
      detection of negative BACTEC MGIT 960 cultures.

PMID- 12202604
TI  - Persistent endemicity of Salmonella bongori 48:z(35):--in Southern Italy:
      molecular characterization of human, animal, and environmental isolates.
AB  - From 1984 to 1999, we collected 31 isolates of the rare serovar Salmonella
      bongori 48:z(35):- in southern Italy. Twenty-four of the isolates were from cases
      of acute enteritis in humans. Pulsed-field gel electrophoresis analysis showed
      that all but one of our isolates were at least 80% similar. Our findings suggest
      that genetically related S. bongori 48:z(35):- strains are endemically
      circulating in southern Italy.

PMID- 12202605
TI  - Comparison of serological detection methods for diagnosis of Ehrlichia canis
      infections in dogs.
AB  - We determined the value of four serological assays for the diagnosis of canine
      monocytic ehrlichiosis by comparing them to the indirect fluorescent-antibody
      assay "gold standard." The specificity of Dip-S-Ticks was significantly lower
      than that of all of the other tests evaluated. The sensitivity of Dip-S-Ticks was
      significantly higher than that of Snap3Dx or the Snap Canine Combo. The
      sensitivity of the rMAP2 enzyme-linked immunosorbent assay (ELISA) was
      significantly higher than that of the Snap Canine Combo. The accuracy levels of
      the rMAP2 ELISA, Snap3Dx, Dip-S-Ticks, and Snap Canine Combo were 97.0, 89.8,
      85.1, and 82.9%, respectively.

PMID- 12202606
TI  - Evaluation of dipstick serologic tests for diagnosis of brucellosis and typhoid
      Fever in egypt.
AB  - Two dipstick assays for the detection of Brucella- and typhoid-specific
      immunoglobulin M, recently developed by the Royal Tropical Institute of The
      Netherlands, were evaluated by use of 85 plasma samples from Egyptian patients.
      Both dipsticks were simple and accurate rapid diagnostic assays, and they can be
      useful adjuncts for the diagnosis of typhoid fever and brucellosis.

PMID- 12202607
TI  - Simple and reliable method for detection and genotyping of hepatitis C virus RNA
      in dried blood spots stored at room temperature.
AB  - We describe a simple, sensitive, and reproducible method for using whole blood
      collected onto filter paper (dried blood spots) for detection and genotyping of
      hepatitis C virus RNA that can be useful in large field studies, particularly in
      settings where collection, preparation, storage, and shipment of samples at
      controlled temperature can be difficult.

PMID- 12202608
TI  - Evaluation of a new dot blot enzyme immunoassay (directigen flu A+B) for
      simultaneous and differential detection of influenza a and B virus antigens from
      respiratory samples.
AB  - We report a prospective evaluation of a new dot blot enzyme immunoassay (EIA)
      method for the direct, rapid, qualitative, simultaneous, and differential
      detection of the influenza A (IA) and B (IB) virus antigen in different
      respiratory samples. The EIA method was compared with the shell vial culture
      system (MDCK cell line) used with the same samples. We studied 160 samples from
      93 (58.1%) pediatric patients (hospital emergency room) and from 67 (41.9%) adult
      patients (sentinel network). Seventy-four(46.2%) samples were considered
      positive; of them, 46 (62.2%) were from pediatric patients and 28 (37.8%) were
      from an adult group (P < 0.05), with overall positive values of 49.9% and 41.7%,
      respectively. All 74 (100%) of the positive samples were isolated in cell culture
      versus the 68.9% that were detected as positive by the new EIA method (P < 0.05).
      Of the 41 samples positive for the IA virus, the EIA detected 34 (82.9%) positive
      samples; of the 33 samples positive for the IB virus, the EIA detected 17 (51.5%)
      positive samples (P < 0.05). No false-positive reaction was detected with the EIA
      method (specificity and positive predictive value of 100%). The overall results
      obtained in the comparison between the new EIA and the shell vial culture had a
      sensibility of 82.9% and predictive negative values of 92.4% for the IA virus and
      51.5% and 84.3%, respectively, for the IB virus. This evaluation shows
      sensitivity and specificity percentages for the new EIA method that is acceptable
      for routine use in IA virus detection. The results obtained were worse for IB
      virus detection, but this new EIA method is actually the only one with the
      capacity to differentiate between the two influenza viruses.

PMID- 12202609
TI  - Molecular characterization confirms the presence of a divergent strain of canine
      coronavirus (UWSMN-1) in Australia.
AB  - Canine coronavirus (CCV) UWSMN-1 was originally identified from an outbreak of
      fatal gastroenteritis in breeding colonies. In this report, we examined whether
      UWSMN-1 represents a novel divergent strain or is the result of recombination
      events between canine and feline coronavirus strains. Sequencing of various
      regions of the spike and polymerase genes confirms that UWSMN-1 is widely
      divergent from other CCV and feline coronavirus strains. These data raise the
      possibility that this strain is the first member of a novel third subtype of CCV.

PMID- 12202610
TI  - Prevalence of blood-borne infectious diseases in blood donors in Ghana.
AB  - Transfusion-transmissible infections among 808 blood donors in Ghana were
      investigated in 1999. Antibody seroprevalences of 3.8, 0.7, 8.4, and 13.5%,
      respectively, for human immunodeficiency virus, human T-cell lymphotrophic virus
      type 1, hepatitis C virus (HCV), and Treponema pallidum were obtained. The
      seroprevalence of HCV infection was confirmed to be 0.9% after supplementary
      testing, and the transfusion risk potential of these pathogens was demonstrated.

PMID- 12202611
TI  - Evaluation of a novel commercial enzyme-linked immunosorbent assay detecting
      Coxiella burnetii-specific immunoglobulin G for Q fever prevaccination screening
      and diagnosis.
AB  - A novel commercially available enzyme-linked immunosorbent assay (ELISA) for
      prevaccination screening and diagnosis of Q fever (PanBio Coxiella burnetii
      immunoglobulin G [IgG] ELISA) was compared to the complement fixation test (CFT),
      and the indirect fluorescent-antibody test (IFAT) was used to resolve discrepant
      results between the other two tests. A total of 214 serum samples was tested. The
      ELISA demonstrated a specificity of 96% (46 of 48 samples) and a sensitivity of
      71% (95 of 134 samples). Of the six serum pairs showing CFT seroconversion, three
      pairs showed a corresponding ELISA seroconversion. No cross-reactivity was
      observed in the ELISA with serum samples from patients with mycoplasma, brucella,
      and chlamydia infections. One of the 13 patients with leptospirosis demonstrated
      a positive result in the ELISA but not in the CFT or the IFAT, and Legionella
      pneumophila serogroup 4 antibody was found in one of the two sera that were false
      positive by ELISA. The results presented in this study suggest that the PanBio Q
      fever IgG ELISA is a specific alternative method for prevaccination testing and
      an aid for the diagnosis of Q fever. This test is suitable for use as a screening
      assay, with CFT and/or IFAT used to confirm negative results.

PMID- 12202612
TI  - A pilot with pain in his leg: thigh abscess caused by Salmonella enterica
      serotype Brandenburg.
AB  - Salmonella enterica serotype Brandenburg is one of the more uncommon serotypes
      isolated from patients with gastroenteritis. Few cases of extraintestinal
      infections with serotype Brandenburg have been documented. The first case of a
      serotype Brandenburg-dependent thigh abscess originating from an atherosclerotic
      pseudoaneurysm of the femoral artery is reported.

PMID- 12202613
TI  - Isolation of Nocardia paucivorans from the cerebrospinal fluid of a patient with
      relapse of cerebral nocardiosis.
AB  - Nocardia paucivorans represents a new species of the genus Nocardia that has
      recently been isolated from bronchial secretions of a patient with chronic lung
      disease. Here, we report on the course of a disseminated infection caused by this
      species: i.e., cerebral and subsequent meningeal manifestations, isolation from
      the cerebrospinal fluid, and in vitro susceptibility to various antimicrobial
      agents.

PMID- 12202614
TI  - First report on Schizophyllum commune from a dog.
AB  - This report describes the first isolation of Schizophyllum commune from a
      granulomatous lesion on the neck of a dog. The biopsy specimen from the lesion
      disclosed granulomatous inflammation with branching fungal hyphae without clamp
      connections. The clinical isolate was identified as S. commune by mycological
      examination and analysis of ribosomal DNA sequences.

PMID- 12202615
TI  - Disseminated infection due to Blastobacter denitrificans following routine
      appendectomy in an adolescent.
AB  - Until now, Blastobacter denitrificans has not been mentioned in the context of
      human infections. A case of severe complication caused by B. denitrificans after
      routine appendectomy in a young girl is described and confirms this organism to
      be an opportunistic human pathogen.

PMID- 12202616
TI  - Enteroaggregative Escherichia coli strains among classical enteropathogenic
      Escherichia coli O serogroups.

PMID- 12202617
TI  - Importance of testing stool specimens for Shiga toxins.

PMID- 12202618
TI  - Acrophialophora fusispora misidentified as Scedosporium prolificans.

PMID- 12202619
TI  - Pulsed-field gel electrophoresis can yield DNA fingerprints of degradation
      susceptible Clostridium difficile strains.

PMID- 12202621
TI  - Urease, the first crystalline enzyme and the proof that enzymes are proteins: the
      work of James B. Sumner.

PMID- 12202622
TI  - The discovery and confirmation of single nucleotide polymorphisms in the human
      p53R2 gene by EST database analysis.
AB  - The human expressed sequence tag (EST) database provides a wealth of resources,
      which can be used to rapidly screen for potential polymorphisms in proteins of
      physiological interest. The human p53R2 gene, a recently identified
      ribonucleotide reductase, plays an important role in DNA repair and is involved
      in the pathway of p53 activity in response to the presence of DNA damage. On the
      basis of the alignment of human EST sequences, we identified three candidate
      polymorphisms at nt 2752, 2759 and 4696 in the 3'-untranslated region of the
      p53R2 gene. The presence of these polymorphisms was confirmed in a Caucasian
      population (n = 82) by allele-specific PCR and PCR/restriction fragment length
      polymorphism analyses. The rare allele frequency at position 4696 (15.5%) is
      higher than either rare allele frequency at position 2752 or 2759 (6 and 6%). Our
      results suggest that the human EST data may serve as a valuable source for the
      rapid identification of genetic variation.

PMID- 12202623
TI  - Ligation of a primer at a mutation: a method to detect low level mutations in
      DNA.
AB  - Detection of low frequency mutations following exposure to mutagens or during the
      early stages of cancer development is instrumental for risk assessment and
      molecular diagnosis. We present a sensitive new method to detect trace levels of
      DNA mutations induced within a large excess of wild-type sequences. The method is
      based on mutation-induced generation of new restriction enzyme recognition sites.
      A DNA sequence is amplified from genomic DNA or cDNA using a high fidelity
      polymerase. The purified PCR product is digested with a restriction enzyme that
      recognizes the newly generated restriction site, partially dephosphorylated and
      ligated with an oligonucleotide at the position of the mutation. The ligated
      oligonucleotide is then utilized in two rounds of PCR to amplify the mutated DNA
      but not the wild-type allele that contains no restriction site. An A-->T
      polymorphism in mRNA (tenascin gene, A(2366)-->T, Asn-->Ile) and a G-->A
      polymorphism in genomic DNA (Ku gene, G(74582)-->A, Val-->Ile), both of which
      generate a restriction site for the enzyme SAU3A1, demonstrate the application.
      Eleven patient samples pre-characterized for the G(74582)-->A polymorphism in the
      repair gene Ku are used to demonstrate the reliability of this approach. This
      technique quantitatively detects the Ku G-->A polymorphism at a mutant frequency
      of 1.6x10(-6) relative to the wild-type allele. Mutations in p53 that are
      frequently induced by mutagens can readily be detected using the present method.
      As an example, using a second enzyme BbvI, a mutation frequently encountered in
      human cancers (G(14154)-->A mutation, p53 codon 245, Arg-->Gln) was detected in
      patient samples. The process does not require radioactivity, utilizes established
      procedures and overcomes several factors known to produce false positives in RFLP
      based assays. The present amplification via primer ligation at the mutation
      (APRIL-ATM) has potential applications in the detection of mutagen-generated
      genetic alterations, early detection of tumor marker mutations in bodily
      discharges and the diagnosis of minimal residual disease.

PMID- 12202624
TI  - A colony color method identifies the vulnerability of mitochondria to oxidative
      damage.
AB  - Mitochondrial dysfunction is a profound feature of cancer cells and is also known
      to cause several mitochondrial diseases. Mutations in mitochondrial DNA (mtDNA)
      have been reported frequently in these diseases. Although many environmental
      agents are known to cause damage to mitochondria, rapid methods need to be
      developed for testing agents that cause mitochondrial dysfunction and are
      involved in the development of mitochondrial and other diseases. Using
      Saccharomyces cerevisiae, we describe the development of a colorimetric method
      that identifies both physical and chemical agents that cause mitochondrial
      dysfunction and mutation of the mitochondrial genome. This method utilizes the
      previously reported ade2 mutant of S.cerevisiae that produces red colonies.
      However, when they lose mitochondrial function the colonies turn white. This
      colorimetric method has helped quantify the vulnerability of mtDNA to oxidative
      agents. Our study reveals that the oxidative agent adriamycin causes both
      mutation and extensive damage to mtDNA, which leads to loss of mtDNA. Our study
      also reveals that the lost mtDNA fragments migrate to the nucleus and integrate
      into the nuclear genome. Furthermore, our analysis reveals that loss of mtDNA
      leads to resistance to oxidative agents. The method described in this paper
      should aid in the rapid identification of environmental and other agents that
      cause mitochondrial dysfunction and mutagenesis, agents that may be involved in
      the development of mitochondrial and other diseases.

PMID- 12202625
TI  - Induction of chromosomal aberrations by dacarbazine in somatic and germinal cells
      of mice.
AB  - Dacarbazine (DTIC) is a chemotherapeutic agent that has been successfully applied
      to treat various types of cancer such as Hodgkin's disease, malignant melanomas,
      soft tissue sarcomas and advanced neuroblastomas. Many of the patients are of
      reproductive age and express concern over the genetic risk of the treatment they
      receive. Therefore, DTIC was tested for its clastogenic effects in somatic and
      germinal cells of mice. In the bone marrow micronucleus assay DTIC induced
      micronuclei that increased linearly in the dose range 0-125 mg/kg. In a dominant
      lethal study DTIC gave a positive response at the dose of 500 mg/kg when
      conceptions occurred 5-16 days after treatment, corresponding to treated
      spermatids and early spermatozoa. The induction of heritable translocations was
      tested in that sensitive period. The observed translocation rate among the F(1)
      progeny of male mice treated with 500 mg/kg DTIC was 2.13% (P < 00.1 against the
      historical control of 0.05%). Assuming linearity of the dose-response effect, the
      point estimate was used to calculate a doubling dose for the induction of
      heritable translocations of 12 mg/kg. Alternatively, an induced translocation
      rate of 41.6x10(-6) per unit dose was calculated. Both figures indicate that an
      increased genetic risk may exist for male patients after chemotherapy with DTIC
      under the assumption that germ cells of mice and humans are equally sensitive to
      the clastogenic effects of DTIC. However, the genetic risk is restricted to
      conceptions within a period of 40 days after the end of chemotherapy, since the
      sensitive stages of spermatogenesis are spermatids and early spermatozoa.

PMID- 12202626
TI  - Micronucleus monitoring of a floriculturist population from western Liguria,
      Italy.
AB  - A biomonitoring study was carried out to investigate whether exposure to complex
      pesticide mixtures in ornamental crop production represents a potential genotoxic
      risk. Exposed and control subjects were selected in western Liguria (Italy). The
      area was chosen for its intensive use of pesticides. The main crops produced were
      roses, mimosas, carnations and chrysanthemums, as ornamental non-edible plants,
      and tomato, lettuce and basil, as edible ones. The levels of micronuclei (MN)
      were analysed in peripheral blood lymphocytes of 107 floriculturists (92 men and
      15 women) and 61 control subjects (42 men and 19 women). A statistically
      significant increase in binucleated cells with micronuclei (BNMN) was detected in
      floriculturists with respect to the control population (4.41 +/- 2.14 MN/1000
      cells versus 3.04 +/- 2.14, P < 0.001). The mean number of BNMN varied as a
      function of sex and age. Smoking habit had no effect on MN frequency. A positive
      correlation between years of farming and MN frequency in peripheral blood
      lymphocytes was observed (r = 0.30, P = 0.02). The conditions of exposure were
      also associated with an increase in cytogenetic damage, with a 28% higher MN
      frequency in greenhouse workers compared with subjects working only outdoors in
      fields. Workers not using protective measures during high exposure activities
      showed an increase in MN frequency. Our findings suggest a potential genotoxic
      risk due to pesticide exposure.

PMID- 12202627
TI  - SCE formation after exposure of CHO cells prelabelled with BrdU or biotin-dUTP to
      various DNA-damaging agents.
AB  - Formation of sister chromatid exchanges (SCE) is a mechanism of repair or bypass
      of DNA damage during S phase. Although SCE have been studied for a long time, the
      types of DNA lesions involved and the role of 5-bromodeoxyuridine (BrdU) in SCE
      formation are a matter of debate. We have developed a novel method of
      differential labelling of sister chromatids with biotin-16-2'-deoxyuridine-5'
      triphosphate (biotin-dUTP) and could show that a substantial proportion of
      radiation-induced SCE arise via damage to BrdU-moieties. The present
      investigations were performed to examine the role of BrdU in the formation of SCE
      by the endonucleases AluI and DNase I, as well as the alkylating agent mitomycin
      C (MMC). CHO cells unifilarily prelabelled with biotin-dUTP or BrdU were treated
      and the frequencies of SCE analysed in the first post-treatment mitoses. AluI
      induced similar frequencies of SCE in cells prelabelled with BrdU or biotin-dUTP.
      DNase I induced significantly more SCE in cells prelabelled with BrdU than with
      biotin-dUTP. MMC induced slightly more SCE in cells labelled with biotin-dUTP
      than BrdU, but the difference was not significant. The possible mechanisms
      responsible for the enhanced SCE frequency following DNase I treatment of cells
      prelabelled with BrdU are discussed.

PMID- 12202628
TI  - Micronuclei frequencies in hospital workers occupationally exposed to low levels
      of ionizing radiation: influence of smoking status and other factors.
AB  - In the context of a medical surveillance program aimed at preventing cancer risk
      from exposure to ionizing radiation, we investigated chromosomal damage in
      peripheral lymphocytes from 37 hospital workers exposed to low levels of ionizing
      radiation and 37 controls. The micronuleus (MN) assay was used as a biomarker of
      genetic damage. The influence of confounding factors like smoking status, age and
      gender was investigated by multiple regression analysis. The results indicated
      that, overall, MN frequency was higher in exposed workers than in controls,
      although the difference was not statistically significant. Interestingly, smoking
      status significantly raised MN frequency among the exposed workers but not among
      controls. This suggests that smoking can influence chromosomal damage induced in
      humans by ionizing radiation. Among both exposed workers and controls, MN
      frequency was found to increase with age. Female gender influenced the increase
      in MN frequency in the exposed group. Our results suggest that the effect of
      cigarette smoking should be carefully factored into genetic monitoring studies
      assessing the risks associated with low level radiation exposure.

PMID- 12202629
TI  - Cytogenetic and oxidative damage induced in human lymphocytes by platinum,
      rhodium and palladium compounds.
AB  - This study of soluble compounds of platinum, palladium and rhodium investigated
      the genotoxic properties of (NH(4))(2)PtCl(4), PtCl(2), PtCl(4),
      (NH(4))(2)PdCl(4), PdCl(2) and RhCl(3) using the human lymphocyte micronucleus
      (MN) assay coupled with fluorescence in situ hybridization (FISH). A
      pancentromeric DNA probe was used to detect both centromere-positive micronuclei
      (C+ MN) as well as centromere-negative micronuclei (C- MN). A modified alkaline
      single cell gel electrophoresis (SCGE) assay was used to evaluate the possible
      role of oxidative damage in genotoxicity of the Pt, Pd and Rh compounds tested.
      Two enzymes, endonuclease III and formamidopyrimidine glycosylase, were used to
      recognize and subsequently cut oxidized pyrimidines and purines, respectively. A
      significant induction of MN by Pt and Rh compounds was observed compared with
      controls, while (NH(4))(2)PdCl(4) and PdCl(2) displayed weak significant MN
      induction. The FISH technique revealed no significant difference in the frequency
      of C+ MN and C- MN for all compounds tested. These findings suggest that MN
      induction is due both to a clastogenic and an aneuploidogenic mechanism. SCGE
      detected an increase in the level of DNA oxidative damage for the Rh compound and
      for Pt(IV) which was also capable of inducing an increase in primary DNA damage
      at all the tested doses. This work highlights the stronger genotoxicity, likely
      mediated by oxidative damage induction, of Pt and Rh compounds compared with Pd
      salts.

PMID- 12202630
TI  - Reversible G(1) arrest by dimethyl sulfoxide as a new method to synchronize
      Chinese hamster cells.
AB  - Dimethyl sulfoxide (DMSO), a well-known differentiation inducer in several
      myeloid cells, also induces a reversible G(1) arrest in many cell lines. We
      recently showed that DMSO induces a G(1) phase arrest in Chinese hamster ovary
      (CHO) cells, by restoring contact inhibition and preventing high density
      dependent apoptosis. CHO cells are frequently used in cell biology and
      mutagenesis studies due to their good growth capacity and ease of manipulation
      but are very difficult to synchronize by serum starvation since they detach from
      monolayers when they reach confluence. In this study we investigated the
      possibility of using DMSO to reversibly synchronize CHO cells in the G(1) phase
      of the cell cycle and analysed whether toxic effects follow the arrest using
      growth curve, sister chromatid exchange and micronuclei assays. We carried out a
      kinetic analysis of the arrest by DMSO and re-entry into the cell cycle after
      drug release by cytofluorimetric analysis of DNA content and bromodeoxyuridine
      incorporation. We show that CHO cells are efficiently and reversibly arrested in
      G(1) by DMSO in concentrations ranging between 1 and 2%. In our experiments, >90%
      of cells grown for 96 h in presence of the drug were arrested in G(1) and
      synchronously re-entered S phase approximately 8-12 h after release. Furthermore,
      expression levels of p27 were down-regulated during G(1) progression and cyclin
      D3 and E expression patterns were similar to those observed after serum
      starvation. No detectable cytotoxicity or genetic damage were induced in G(1)
      released cells as revealed by the tests employed. Our results show that DMSO is a
      very powerful inducer of G(1) synchronization in CHO cells without detectable
      cytotoxic or genetic effects in cell populations released from G(1) arrest. DMSO
      synchronization represents a model system in which to analyse protein activities
      regulating G(1) progression and investigate the response of G(1) cells to mutagen
      treatments.

PMID- 12202631
TI  - Nasal cell micronuclei, cytology and clinical symptoms in stainless steel
      production workers exposed to chromium.
AB  - The objective of the present study was to determine whether workers in stainless
      steel production with low exposure to various forms of chromium show an increase
      in micronucleated nasal cells or an excess of nasal symptoms or disease.
      Altogether, 48 workers employed in a stainless steel production chain were
      studied, 29 of them in the steel melting shop with exposure to hexavalent
      chromium (Cr(6+)), 14 in the sintering and crushing departments of the
      ferrochromium plant with exposure to trivalent chromium (Cr(3+)) and five in the
      mine with exposure to chromite ore (Cr(3+)). Thirty-nine workers from the cold
      rolling mill, with very low exposure to chromium, served as referents. All the
      subjects were never smokers with a minimum of 14 years employment in the same
      department. There were no significant differences between the exposure groups and
      the referents regarding the mean frequency of centromere-negative or centromere
      positive micronuclei (studied by pancentromeric fluorescence in situ
      hybridization), nasal diseases and symptoms or mucociliary clearance of the nasal
      cavity. No statistically significant differences in the incidence of cell atypia
      or inflammatory cells were detected between the exposed workers and the reference
      group, except for an increase in lymphocytes among the chromite ore workers.
      Anterior rhinoscopy indicated slight inflammatory changes in nasal mucosa and
      secretion more often in the Cr(6+) and Cr(3+) groups than in the referents, the
      Cr(6+)-exposed workers showing more livid or oedemic epithelium. In conclusion,
      the stainless steel production workers, with low exposure to dusts or fumes
      containing hexavalent or trivalent chromium, did not show clinical changes in the
      nasal mucosa or an increase in nasal cell micronuclei or symptoms of nasal
      diseases, except for slight changes in the nasal epithelium and secretion.

PMID- 12202632
TI  - Oestrogens induce G(1) arrest in benzo[a]pyrene-treated MCF-7 breast cells whilst
      enhancing genotoxicity and clonogenic survival.
AB  - Carcinogens, such as benzo[a]pyrene (B[a]P), allow cells to evade G(1) arrest
      (the stealth property), thus increasing the chance that DNA damage will
      ultimately result in transformation. In this study we have investigated the
      effects of B[a]P in MCF-7 cells incubated in the presence or absence of
      oestrogens (beta-oestradiol, oestrone or oestriol). The cytokinesis block
      micronucleus assay was used to examine cells for chromosomal damage. Micronuclei
      were scored in 500 binucleate cells per treatment. Increased micronucleus
      formation (3-fold) occurred following 24 h treatment with 10(-6) M B[a]P alone.
      Following co-treatment with either 10(-9) M beta-oestradiol, 10(-8) M oestrone or
      10(-8) M oestriol, 2- to 3-fold increases in micronuclei were observed with 10(
      8) M B[a]P. When MCF-7 cells were pre-incubated for 96 h with 10(-9) M beta
      oestradiol, 10(-8) M oestrone or 10(-8) M oestriol prior to the addition of B[a]P
      for 24 h, up to a 5-fold enhanced sensitivity to micronucleus formation was
      observed with beta-oestradiol and oestrone, while oestriol appeared to reduce
      levels of micronucleus formation. B[a]P-induced decreases in cell proliferation
      (per cent binucleate cells) and plating efficiency were reversed by all three
      oestrogens. Analysis of cell cycle distributions revealed that treatment with
      oestrogens or B[a]P alone did not induce marked effects on cell cycle
      distributions. However, in combination oestrogen and B[a]P induced increases in
      G(0)/G(1), decreases in S phase and increases in G(2)/M. This work suggests that
      whilst oestrogens appear to enhance carcinogen-induced DNA damage, they also
      appear, paradoxically, to trigger mechanisms that facilitate clonogenic survival,
      which may be relevant to breast cancer initiation.

PMID- 12202633
TI  - Comparative potencies of induction of point mutations and genetic duplications by
      the methylating agents methylazoxymethanol and dimethyl sulfate in bacteria.
AB  - Methylazoxymethanol (MAM) and dimethyl sulfate (DMS) are mutagens whose genetic
      effects can be ascribed to the methylation of DNA. While both methylate the N7
      position of guanine heavily, only MAM strongly methylates the O(6) position of
      guanine. We evaluated the relative effectiveness and specificity of MAM and DMS
      in bacterial assays for the induction of point mutations and the formation of
      chromosomal duplications by genetic recombination. Salmonella typhimurium strain
      TS1121 was used to measure the formation of genetic duplications on the basis of
      the aroC321 allele and mutations by reversion of the hisG46 allele. Specific base
      pair substitutions and frameshift mutations were measured in a reversion assay
      based on lacZ alleles of Escherichia coli. The results show MAM to be the more
      potent mutagen and DMS the stronger recombinagen in the Salmonella assay. In the
      lacZ assay DMS induced several classes of base pair substitutions (GC-->AT
      transitions, GC-->TA transversions and AT-->TA transversions), as well as lower
      frequencies of +1, -1 and -2 frameshift mutations. The activity of MAM as a base
      pair substitution mutagen was more specific than that of DMS, inducing only GC-
      >AT transitions. It also induced +G, -G, -A and -CG frameshift mutations, though
      more weakly than it induced GC-->AT transitions. Long known as a base pair
      substitution mutagen, the induction of frameshifts by MAM was unexpected. The
      results show that both DMS and MAM are effective inducers of base pair
      substitutions and modest inducers of frameshifts and that DMS exhibits a broader
      spectrum of mutagenic activity than does MAM.

PMID- 12202634
TI  - Concerning the CYP17 MspA1 polymorphism and breast cancer risk: a meta-analysis.

PMID- 12202636
TI  - Severe impairment of secretory Ig production in parotid saliva of Down syndrome
      individuals.

PMID- 12202637
TI  - Two decades of computerized information technologies in dental radiography.

PMID- 12202638
TI  - Characteristics of mastication in the anodontic mouse.
AB  - Teeth and periodontal mechanoreceptors play important roles in regulating jaw
      movements during mastication. However, little is known concerning how jaw
      movements develop without tooth eruption. To answer this question, we studied
      masticatory behavior in the osteopetrotic mouse, where tooth eruption does not
      occur and periodontal mechanoreceptors are missing. A masticatory sequence of the
      osteopetrotic mouse was divided into two stages: incision and chewing. Incision
      is characterized by small amplitude and rapid (7 Hz) open-close jaw movements,
      while slow (5 Hz) and large amplitude open-close jaw movements characterize
      chewing. The frequency and properties of jaw movements were comparable with those
      in the normal mouse, though the osteopetrotic mouse had a higher cycle number
      during incision than did the normal mouse. These results indicate that conversion
      from sucking to mastication occurs in the anodontic mouse, and the central
      pattern generator producing the masticatory rhythm develops almost normally
      without tooth eruption.

PMID- 12202639
TI  - Effect of serotonin (5-HT) on trigeminal rhythmic activities generated in in
      vitro brainstem block preparations.
AB  - We used rat isolated brainstem block preparations to analyze the functional roles
      of serotonin receptors in the generation of trigeminal rhythmic activities. We
      previously reported that trigeminal rhythmic activities could be induced by some
      pharmacological applications in an isolated brainstem preparation with a rostral
      boundary at the border between the inferior and superior colliculus, and a caudal
      border at the level of the rostral facial nucleus. However, the same stimulation
      did not induce trigeminal rhythmic activities in a whole brainstem block
      preparation with the same rostral boundary and a caudal border at the obex level.
      In the present study, both the 5-HT(1A) phthalimido-butyl-piperazine, and the 5
      HT(2C) agonist, 1-2,5-dimethoxy-4-iodophenyl-2-aminopropane, combined with N
      methyl-D,L-aspartate and bicuculline, elicited trigeminal rhythmic activities in
      a whole brainstem block preparation. Our results suggest that serotonin has both
      facilitation and inhibition effects on the generation of trigeminal rhythmic
      activities in an isolated brainstem block preparation in vitro.

PMID- 12202640
TI  - The localization of matrix metalloproteinase-20 (MMP-20, enamelysin) in mature
      human teeth.
AB  - MMP-20 (enamelysin), the matrix metalloproteinase family member discovered in the
      enamel organ, has also been detected in odontoblasts during dentin formation. We
      studied the presence and localization of MMP-20 in mature human teeth in health
      and disease. In immunohistochemistry, MMP-20-positive staining was observed most
      intensively in the radicular odontoblastic layer and also in dilated dentinal
      tubuli of caries lesions. By Western blotting, MMP-20 was detected in
      odontoblasts and pulp tissue of both sound and carious teeth, in dentinal fluid
      and dentin of sound teeth, but not in soft carious dentin. We conclude that MMP
      20 produced during primary dentinogenesis is incorporated into dentin and may be
      released during caries progression. The main cellular source of MMP-20 in the
      dentin-pulp complex is the odontoblasts, which secrete MMP-20 into the dentinal
      fluid.

PMID- 12202641
TI  - Bone strain patterns of the zygomatic complex in response to simulated orthopedic
      forces.
AB  - Craniofacial bone strain upon orthopedic loading has rarely been characterized,
      despite its fundamental importance in our understanding of the anabolic and
      catabolic effects of orthopedic forces. The present study tested the hypothesis
      that zygomatic bone strain is modulated upon loading by headgear, a device widely
      used in craniofacial orthopedics. Ramp forces from 0 to 50 Newtons were applied
      via headgear attached to the permanent maxillary first molars in four juvenile
      and five adult human skulls. The average peak bone strain of the juvenile
      temporal articular eminence was significantly higher than the adult articular
      eminence (p < 0.05). Contrasting bone strain patterns were identified in the
      zygomatic arch: tensile in its lateral surface but compressive in its medial
      surface. The peak bone strain of the temporal articular eminence and the
      zygomatic arch both depend upon loading direction. Thus, headgear-generated
      orthopedic forces evoke bending of the zygomatic arch and stresses of the
      temporal articular eminence in vitro, suggesting the need to verify whether bone
      strain induces in vivo bone modeling and remodeling.

PMID- 12202642
TI  - Edentulation alters material properties of cortical bone in the human mandible.
AB  - Ridge resorption following edentulation has been documented clinically, but the
      effects of tooth loss on the material properties of mandibular cortical bone have
      received little study. Material properties and their structural basis are
      essential for our understanding of bone quality in the edentulous mandible and
      are of interest as a tissue-level model for functional adaptation. This study's
      aim was to determine material property variability in the edentulous mandible,
      and to compare it with data from a previous study of dentate mandibles. Forty
      four cortical samples were removed from each of 10 adult fresh edentulous
      mandibles. Cortical thickness and density were measured. Material properties were
      calculated from ultrasonic velocities. Mandibular cortical bone in the edentulous
      mandibles differed from that of dentate mandibles in cortical thickness, elastic
      and shear moduli, anisotropy, and orientation of the axis of maximum stiffness.
      These results suggest that cortical microstructural changes accompany ridge
      resorption following edentulation.

PMID- 12202643
TI  - Dynamic properties of bovine temporomandibular joint disks change with age.
AB  - The temporomandibular joint disk exhibits morphological and biochemical age
      related changes. However, the possible age-related changes of the dynamic
      viscoelasticity in the disk are unclear. We tested the hypothesis that the
      dynamic viscoelastic properties of the disk change with age. Thirty-six disks
      from young-adult, adult, and mature-adult cattle were used for dynamic tensile
      tests. In all disks, the magnitudes of the complex modulus, the storage modulus,
      and the loss modulus increased as the frequency increased. The mature-adult disks
      had higher values of these moduli than did the younger disks. The loss tangent
      ranged from 0.1 to 0.3, which means that the disk has relatively large elasticity
      and relatively small viscosity. It was concluded that both the elasticity and
      viscosity of the disk increase with age. This may reflect age-related changes in
      biochemical composition.

PMID- 12202644
TI  - Influence of connector design on fracture probability of ceramic fixed-partial
      dentures.
AB  - Fracture of ceramic fixed-partial dentures (FPDs) tends to occur in the connector
      area because of stress concentrations. The objective of this study was to test
      the hypothesis that the radius of curvature at the gingival embrasure of the FPD
      connector significantly affects the fracture resistance of three-unit FPDs. Two
      three-dimensional finite element models (FEMs), representing two FPD connector
      designs, were created in a manner corresponding to that described in a previous
      experimental study (Oh, 2002). We performed fractographic analysis and FEM
      analyses based on CARES (NASA) post-processing software to determine the crack
      initiation site as well as to predict the characteristic strength, the location
      of peak stress concentrations, and the risk-of-rupture intensities. A good
      correlation was found between the experimentally measured failure loads and those
      predicted by FEM simulation analyses. Fractography revealed fracture initiation
      at the gingival embrasure, which confirms the numerically predicted fracture
      initiation site. For the designs tested, the radius of curvature at the gingival
      embrasure strongly affects the fracture resistance of FPDs.

PMID- 12202645
TI  - A nanoleakage perspective on bonding to oxidized dentin.
AB  - The mechanism responsible for sodium-hypochlorite-induced reduction in dentin
      bond strength and its reversal with reducing agents is unknown. This study
      examined the relationship between nanoleakage and reversal of compromised bonding
      to oxidized dentin. Acid-etched dentin was completely depleted of demineralized
      collagen matrix when sodium hypochlorite was used. Specimens were bonded with two
      single-bottle dentin adhesives. They were immersed in ammoniacal silver nitrate
      for 24 hrs before being processed for transmission electron microscopy. For both
      adhesives, tensile bond strengths of acid-etched dentin were significantly
      reduced after sodium hypochlorite treatment, but were reversed when sodium
      ascorbate was used. After sodium hypochlorite application, reticular nanoleakge
      patterns in hybrid layers were replaced by vertical, shag-carpet-like patterns
      along the demineralization front. This type of nanoleakage was completely
      eliminated after sodium ascorbate treatment with the materials tested. Residual
      sodium hypochlorite within the porosities of mineralized dentin may result in
      incomplete resin polymerization, and hence compromised bond strength.

PMID- 12202646
TI  - HEMA bound to self-protein promotes auto-antibody production in mice.
AB  - While several studies report that acrylic monomers contained in dental materials
      may cause hypersensitivity reactions, little is known of the associated immune
      response. Here we address the potential of 2-hydroxyethyl-methacrylate (HEMA) to
      bind to endogenous protein and elicit auto-antibody production in vivo. Albumin
      was incubated with HEMA at various times and pH. Following confirmation of the
      conjugation by inhibition of trinitrophenyl (TNP) binding, female Balb/c mice
      received HEMA conjugated to mouse serum albumin (MSA) in Freund's incomplete
      adjuvant or saline subcutaneously. ELISA was used to determine the serum antibody
      responses to native and modified MSA. IL-2 production in spleen cell cultures
      stimulated with HEMA-conjugated MSA was measured. HEMA reacted with serum albumin
      at physiological conditions. HEMA-conjugated MSA induced IL-2 secretion and
      production of IgG antibodies to native MSA. The results suggest that modification
      of an endogenous protein like serum albumin with HEMA may defeat the control of
      immune responses to this self-protein.

PMID- 12202648
TI  - Comparing the costs of three sealant delivery strategies.
AB  - We analyzed the cost-effectiveness of 3 sealant delivery strategies: Seal all
      (SA), seal children assessed to be at risk by screening (TARGET), and seal none
      (SN). We assumed a nine-year analytic horizon, a 3% discount rate, and zero
      screening costs. Estimates for sealant costs ($27.00) and restoration costs
      ($73.77), annual caries increment (0.0624 surfaces), sealant failure rate (20% in
      yr 1 and 3% thereafter), annual amalgam failure rate (4.6%), and sensitivity
      (0.635) and specificity (0.795) of screening were obtained from published
      studies. Under baseline assumptions, TARGET dominated (cost less and reduced
      caries) SA and SN. If annual caries increment exceeded 0.095 surfaces, SA
      dominated TARGET, and if increment exceeded 0.05 surfaces, TARGET dominated SN.
      If sealant costs decreased to $6.00 (reported cost for school programs), TARGET
      dominated SN for caries increments exceeding 0.007 surfaces, and SA dominated
      TARGET for caries increments exceeding 0.034 surfaces.

PMID- 12202647
TI  - An abbreviated caries clinical trial design validated over 24 months.
AB  - Conventional caries trials last from 24 to 36 months. This study evaluated
      whether the previously established difference in efficacy between 1000- and 2500
      ppm-fluoride dentifrices could be detected after 12 months. Caries was assessed
      by clinical visual assessment (CVA-simplified version of Dundee Selectable
      Threshold Method - DSTM), bitewing radiography, and Fiber Optic Transillumination
      (FOTI). Changes in status for individual surfaces were classified by means of pre
      prepared matrices as 0 (unchanged), +1 (initiation or progression), or -1
      (regression) and summed for each subject to yield an event score. Mean group
      event scores were calculated for each product. DSTM at the D(1) [enamel and
      dentin] threshold showed significant inter-group differences in mean event scores
      (p < 0.003) and D(1)MFS increment (< 0.007) at 12 months; these were confirmed at
      24 months by traditional increment analysis (CVA & FOTI at the D(3) (dentin only)
      threshold + radiography, p < 0.03). This study confirms the validity of an
      abbreviated trial protocol.

PMID- 12202649
TI  - Effect of sustained contraction on motor unit action potentials and EMG power
      spectrum of human masticatory muscles.
AB  - The sequelae of a sustained clench are incompletely understood. Our experimental
      questions were to compare the responses of men and women, to compare masseter and
      anterior temporalis muscles, and to test hypotheses for the reduction of the
      median frequency of power spectra. We recorded duration, amplitude, number of
      phases, and area of the motor unit action potential before and after a sustained
      clench and the median frequency of the electromyographic power spectrum in 41
      subjects. After the clench, the median frequency was lower, the action potential
      duration longer, the number of phases increased, and the area larger, but the
      amplitude was not different. Males and females failed to differ. Compared with
      the temporalis, the masseter had a lower median frequency, longer duration,
      larger number of phases, and increased area. Our results are consistent with a
      decrease in the conduction velocity of the muscle action potential as an
      explanation of the spectral shift.

PMID- 12202650
TI  - Capsaicin-induced muscle pain alters the excitability of the human jaw-stretch
      reflex.
AB  - The pathophysiology of painful temporomandibular disorders is not fully
      understood, but evidence suggests that muscle pain modulates motor function in
      characteristic ways. This study tested the hypothesis that activation of
      nociceptive muscle afferent fibers would be linked to an increased excitability
      of the human jaw-stretch reflex and whether this process would be sensitive to
      length and velocity of the stretch. Capsaicin (10 micro g) was injected into the
      masseter muscle to induce pain in 11 healthy volunteers. Short-latency reflex
      responses were evoked in the masseter and temporalis muscles by a stretch device
      with different velocities and displacements before, during, and after the pain.
      The normalized reflex amplitude increased with an increase in velocity at a given
      displacement, but remained constant with different displacements at a given
      velocity. The normalized reflex amplitude was significantly higher during pain,
      but only at faster stretches in the painful muscle. Increased sensitivity of the
      fusimotor system during acute muscle pain could be one likely mechanism to
      explain the findings.

PMID- 12202651
TI  - Treatment of advanced non-small-cell lung cancer with two-drug combinations.

PMID- 12202652
TI  - Imatinib GIST keeps finding new indications: successful treatment of
      dermatofibrosarcoma protuberans by targeted inhibition of the platelet-derived
      growth factor receptor.

PMID- 12202653
TI  - Diet and trend in prostate-specific antigen: inferences for prostate cancer risk.

PMID- 12202654
TI  - Size of the androgen receptor CAG repeat and prostate cancer: does it matter?

PMID- 12202655
TI  - Of what value is uracil/tegafur plus leucovorin to colorectal cancer patients?

PMID- 12202656
TI  - Lumping versus splitting: the splitters take this round.

PMID- 12202657
TI  - Paclitaxel plus carboplatin versus gemcitabine plus paclitaxel in advanced non
      small-cell lung cancer: a phase III randomized trial.
AB  - PURPOSE: We conducted this randomized study comparing the activity and toxicity
      of paclitaxel and gemcitabine (PG) and paclitaxel and carboplatin (PC)
      combinations for the treatment of advanced non-small-cell lung cancer (NSCLC).
      PATIENTS AND METHODS: Chemotherapy-naive patients were randomized to paclitaxel
      200 mg/m(2) on day 1 plus either carboplatin at an area under the concentration
      time curve of 6 on day 1 (group A) or gemcitabine 1,000 mg/m(2) on days 1 and 8
      (group B) every 3 weeks. A retrospective cost analysis was conducted using
      Student's t test to compare independent samples between groups. RESULTS: A total
      of 509 patients (group A, 252 patients; group B, 257 patients) were enrolled; all
      characteristics were well balanced. The median survival time was 10.4 months (95%
      confidence interval [CI], 8.8 to 12 months) for group A and 9.8 months (95% CI,
      8.0 to 11.7 months) for group B (P =.32). Respective 1-year survival rates were
      41.7% and 41.4%. The response rate for group A was 28.0% (2% complete response
      [CR], 26% partial response [PR] [95% CI, 22% to 34%]), and the response rate for
      group B was 35.0% (5% CR, 30% PR) [95% CI, 29% to 41%]) (P =.12). Toxicity was
      mild. Grades 3/4 neutropenia, thrombocytopenia, and anemia for groups A and B
      were seen in 15% and 15%, 2% and 1%, and 5% and 2%, respectively. The mean total
      cost (outpatient clinic visits plus chemotherapy drug fee) for group A (euro;
      7,612.64) versus group B (euro; 7,484.77) was not statistically significant (P
      <.66). CONCLUSION: The PG combination is as equally active and well tolerated as
      the PC combination in patients with advanced NSCLC.

PMID- 12202658
TI  - Molecular targeting of platelet-derived growth factor B by imatinib mesylate in a
      patient with metastatic dermatofibrosarcoma protuberans.
AB  - PURPOSE: Dermatofibrosarcoma protuberans is caused by activation of the platelet
      derived growth factor B (PDGFB) receptor, a transmembrane tyrosine kinase. We
      investigated the response of dermatofibrosarcoma protuberans to the tyrosine
      kinase inhibitor imatinib mesylate. PATIENTS AND METHODS: A patient with
      unresectable, metastatic dermatofibrosarcoma protuberans received imatinib
      mesylate (400 mg bid). Response to therapy was assessed by
      [18F]fluorodeoxyglucose (FDG) positron emission tomography, magnetic resonance
      imaging, and histopathologic and immunohistochemical evaluation. RESULTS: The
      patient was treated for 4 months with imatinib mesylate. The hypermetabolic
      uptake of FDG fell to background levels within 2 weeks of treatment, and the
      tumor volume shrank by over 75% during the 4 months of therapy, allowing for
      resection of the mass. There was no residual viable tumor in the resected
      specimen, indicating a complete histologic response to treatment with imatinib
      mesylate. CONCLUSION: Imatinib mesylate is highly active in dermatofibrosarcoma
      protuberans. The dramatic response seen in this patient demonstrates that
      inhibition of PDGFB receptor tyrosine kinase activity can significantly impact
      viability of at least one type of solid tumor.

PMID- 12202659
TI  - Lack of effect of a low-fat, high-fruit, -vegetable, and -fiber diet on serum
      prostate-specific antigen of men without prostate cancer: results from a
      randomized trial.
AB  - PURPOSE: To determine whether a diet low in fat and high in fruits, vegetables,
      and fiber may be protective against prostate cancer by having an impact on serial
      levels of serum prostate-specific antigen (PSA). METHODS: Six hundred eighty-nine
      men were randomized to the intervention arm and 661 to the control arm. The
      intervention group received intensive counseling to consume a diet low in fat and
      high in fiber, fruits, and vegetables. The control group received a standard
      brochure on a healthy diet. PSA in serum was measured at baseline and annually
      thereafter for 4 years, and newly diagnosed prostate cancers were recorded.
      RESULTS: The individual PSA slope for each participant was calculated, and the
      distributions of slopes were compared between the two groups. There was no
      significant difference in distributions of the slopes (P =.99). The two groups
      were identical in the proportions of participants with elevated PSA at each time
      point. There was no difference in the PSA slopes between the two groups (P =.34)
      and in the frequencies of elevated PSA values for those with elevated PSA at
      baseline. Incidence of prostate cancer during the 4 years was similar in the two
      groups (19 and 22 in the control and intervention arms, respectively).
      CONCLUSION: Dietary intervention over a 4-year period with reduced fat and
      increased consumption of fruits, vegetables, and fiber has no impact on serum PSA
      levels in men. The study also offers no evidence that this dietary intervention
      over a 4-year period affects the incidence of prostate cancer during the 4 years.

PMID- 12202660
TI  - Racial variation in CAG repeat lengths within the androgen receptor gene among
      prostate cancer patients of lower socioeconomic status.
AB  - PURPOSE: To evaluate (1) whether there were racial differences in the androgen
      receptor gene CAG repeat length and in clinical or laboratory attributes of
      prostate cancer at the time of diagnosis; (2) whether there were differences in
      race, Gleason score, prostate-specific antigen (PSA) level, and stage at
      diagnosis by androgen receptor gene CAG repeat length; and (3) whether
      sociodemographic, clinical, and laboratory based factors might be associated with
      advanced-stage prostate cancer. To our knowledge, our study is the first to
      report on CAG repeat lengths in a cohort of prostate cancer patients, which
      includes large numbers of African-American men. METHODS: CAG repeat lengths on
      the androgen receptor gene were evaluated for 151 African-American and 168 white
      veterans with prostate cancer. The chi(2) test, t test, and logistic regression
      analyses were used to evaluate the associations between CAG repeat lengths and
      race, stage, histologic grade, and PSA levels at diagnosis. RESULTS: The mean age
      of the cohort at the time of diagnosis was 68.7 years. At presentation, 42.0% had
      stage D prostate cancer, 26.5% had Gleason scores of 8 to 10, and 53.0% had PSA
      levels >/= 10 ng/dL. Mean androgen receptor gene CAG repeat length for white
      veterans was 21.9 (SD, 3.5) versus 19.8 (SD, 3.2) for African-American veterans
      (P =.001). Men with shorter CAG repeats were more likely to have stage D prostate
      cancer (P =.09) but were not more likely to have a higher PSA concentration or
      Gleason score. CONCLUSION: In this cohort of men with prostate cancer, short CAG
      repeat length on the androgen receptor gene was associated with African-American
      race and possibly with higher stage but not with other clinical or pathologic
      findings.

PMID- 12202661
TI  - Multicenter phase III study of uracil/tegafur and oral leucovorin versus
      fluorouracil and leucovorin in patients with previously untreated metastatic
      colorectal cancer.
AB  - PURPOSE: This phase III study was designed to demonstrate equivalence in survival
      of oral uracil/tegafur (UFT) and oral leucovorin (LV) to conventional intravenous
      (IV) fluorouracil (5-FU) and LV in previously untreated metastatic colorectal
      carcinoma. Safety was also compared. PATIENTS AND METHODS: Eight hundred sixteen
      patients were randomized to receive either UFT (300 mg/m(2)/d) and LV (75 or 90
      mg/d) for 28 days every 35 days or IV bolus 5-FU (425 mg/m(2)/d) and LV (20
      mg/m(2)/d) for 5 days every 28 days. RESULTS: UFT/LV produced survival comparable
      to the IV 5-FU/LV regimen. Median survival was 12.4 months (95% confidence
      interval [CI], 11.2 to 13.6 months) with UFT/LV and 13.4 months (95% CI, 11.6 to
      15.4 months) with 5-FU/LV (P =.630). The hazard ratio for survival was 0.964
      (95.6% CI, 0.826 to 1.125), supporting equivalent survival. The overall response
      rate did not differ between treatment arms (UFT/LV, 11.7%; 5-FU/LV, 14.5%; P
      =.232). Median time to progression favored 5-FU/LV (UFT/LV, 3.5 months; 5-FU/LV,
      3.8 months; P =.011), but tumor assessment schedules differed between arms.
      UFT/LV significantly improved safety compared with 5-FU/LV. Diarrhea, nausea and
      vomiting, and stomatitis and mucositis were significantly less frequent with
      UFT/LV, as was myelosuppression. Patients treated with UFT/LV had fewer episodes
      of febrile neutropenia (P <.001) and documented infections (P <.05). Increased
      bilirubin, without other liver function abnormalities, was observed more often
      with UFT/LV (P <.001). Concomitant medications were more frequent with 5-FU/LV,
      including use of antibiotics, growth factors, and antiemetics. CONCLUSION: UFT/LV
      provided a safer, more convenient oral alternative to a standard bolus IV 5-FU/LV
      regimen for metastatic colorectal cancer while producing equivalent survival.

PMID- 12202662
TI  - Randomized comparative study of tegafur/uracil and oral leucovorin versus
      parenteral fluorouracil and leucovorin in patients with previously untreated
      metastatic colorectal cancer.
AB  - PURPOSE: This phase III study compared the time to progression (TTP) of an oral
      regimen of dihydropyrimidine dehydrogenase inhibitory fluoropyrimidine composed
      of a fixed combination of tegafur and uracil in a 1:4 molar ratio (UFT) and
      leucovorin (LV) to intravenous (IV) fluorouracil (5-FU) and LV in previously
      untreated metastatic colorectal carcinoma (CRC) patients. Secondary end points
      were survival, tumor response, safety, and quality of life. PATIENTS AND METHODS:
      Between May 1996 and July 1997, 380 patients were randomized to receive either
      UFT (300 mg/m(2)/d) and LV (90 mg/d), administered for 28 days every 35 days, or
      5-FU (425 mg/m(2)/d) and LV (20 mg/m(2)/d), given IV for 5 days every 35 days.
      RESULTS: No statistically significant difference in TTP was observed between
      treatments. With 320 events assessed, the median TTP was 3.4 months (95%
      Confidence interval [CI], 2.6 to 3.8) on UFT/LV and 3.3 months (95% CI, 2.5 to
      3.7) on 5-FU/LV (P =.591, stratified log-rank test). There were no statistically
      significant differences in survival, tumor response, duration of response, and
      time to response. Substantial safety benefits were observed in patients treated
      with UFT/LV. They experienced significantly less stomatitis/mucositis (P <.001)
      and myelosuppression, resulting in fewer episodes of febrile neutropenia (P
      <.001) and less documented infection (P =.04). Concomitant medication usage was
      significantly greater on 5-FU/LV (P =.010). With respect to quality of life,
      after correcting for baseline imbalances, there were no significant differences
      between treatments for any scale, except diarrhea. CONCLUSION: The oral UFT/LV
      regimen failed to achieve improved TTP; however, the study confirms significant
      safety improvements compared with bolus IV 5-FU/LV for the first-line treatment
      of metastatic CRC.

PMID- 12202663
TI  - Revision of the American Joint Committee on Cancer staging system for breast
      cancer.
AB  - PURPOSE: To revise the American Joint Committee on Cancer staging system for
      breast carcinoma. MATERIALS AND METHODS: A Breast Task Force submitted
      recommended changes and additions to the existing staging system that were (1)
      evidence-based and/or consistent with widespread clinical consensus about
      appropriate diagnostic and treatment standards and (2) useful for the uniform
      accrual of outcome information in national databases. RESULTS: Major changes
      included the following: size-based discrimination between micrometastases and
      isolated tumor cells; identifiers to indicate usage of innovative technical
      approaches; classification of lymph node status by number of involved axillary
      lymph nodes; and new classifications for metastasis to the infraclavicular,
      internal mammary, and supraclavicular lymph nodes. CONCLUSION: This revised
      staging system will be officially adopted for use in tumor registries in January
      2003.

PMID- 12202664
TI  - Dose-dense anthracycline-based chemotherapy for node-positive breast cancer.
AB  - PURPOSE: Theoretical considerations and clinical experience suggest that dose
      dense chemotherapy may be superior to other approaches using the same drugs. We
      studied a dose-dense combination of doxorubicin and cyclophosphamide, with or
      without fluorouracil, as adjuvant therapy. PATIENTS AND METHODS: Patients with
      resected breast cancer were treated if they were node-positive and estrogen
      receptor-negative, positive for overexpression of Her-2-neu, or had four or more
      involved nodes. Doxorubicin was given weekly to a total dose of 480 mg/m(2).
      Cyclophosphamide 60 mg/m(2) was given daily by mouth during the period of
      doxorubicin treatment. The first 30 patients received fluorouracil at 300
      mg/m(2)/wk intravenously concurrently with doxorubicin administration. In the
      last 22, it was omitted because of symptomatic hand-foot syndrome in the majority
      of patients. Filgrastim (granulocyte colony-stimulating factor [G-CSF]) was
      administered during chemotherapy every day except the day of intravenous
      administration and continued until 1 week after the completion of the
      chemotherapy. RESULTS: Between October 20, 1992, and June 10, 1997, we enrolled
      52 patients. The mean delivered dose-intensity for doxorubicin was 18.6
      mg/m(2)/wk. Hospitalization was required in 6% of patients for reversible febrile
      neutropenia. There were no acute treatment-related deaths, but one patient
      subsequently died of acute leukemia with a characteristic translocation for
      anthracycline-related exposure. At 5 years, the event-free survival was 86% for
      all patients (95% confidence interval, 75% to 95%). CONCLUSION: Continuous dose
      dense chemotherapy with G-CSF support produced encouraging results, which seem to
      be superior to those expected with "standard" doxorubicin and cyclophosphamide
      chemotherapy. It deserves a test in the form of a randomized trial where this
      approach to anthracycline-based treatment is compared with intermittent
      administration.

PMID- 12202665
TI  - Phase II randomized trial of temozolomide and concurrent radiotherapy in patients
      with brain metastases.
AB  - PURPOSE: To determine the efficacy, tolerability, and safety of concurrent
      temozolomide and radiotherapy in patients with previously untreated brain
      metastases. PATIENTS AND METHODS: Fifty-two patients with brain metastases from
      solid tumors were randomized to oral temozolomide (75 mg/m(2)/d) concurrent with
      40-Gy fractionated conventional external-beam radiotherapy (2 Gy, 5 d/wk) for 4
      weeks versus 40-Gy radiotherapy alone. The group receiving temozolomide and
      radiotherapy continued temozolomide therapy (200 mg/m(2)/d) for 5 days every 28
      days for an additional six cycles. The primary end points were radiologic
      response and neurologic symptom evaluation. RESULTS: The objective response rate
      was significantly (P =.017) improved in patients receiving temozolomide and
      radiotherapy versus radiotherapy alone. Among 24 patients assessable for response
      in the temozolomide group, 23 (96%) of 24 responded, including nine (38%)
      patients with a complete response and 14 (58%) patients with a partial response.
      With radiotherapy alone, 14 (67%) of 21 assessable patients responded, including
      seven (33%) complete responses and seven (33%) partial responses. There was
      marked neurologic improvement in the group receiving temozolomide, and the
      proportion of patients requiring corticosteroids 2 months after treatment was
      lower in the temozolomide group compared with radiotherapy alone (67% v 91%,
      respectively). Daily temozolomide concurrent with radiotherapy was generally well
      tolerated; however, grade >or= 2 nausea (48% v 13%, P =.13) and vomiting (32% v
      0%, P =.004) were significantly increased in the temozolomide group. Hematologic
      toxicity was predictable and reversible. CONCLUSION: Temozolomide is safe, and a
      significant improvement in response rate was observed when administered in
      combination with radiotherapy in patients with previously untreated brain
      metastases. A larger randomized trial is warranted to verify these results.

PMID- 12202666
TI  - Correlation of smoking history and other patient characteristics with major
      complications of pelvic radiation therapy for cervical cancer.
AB  - PURPOSE: The purpose of this study was to identify patient-related factors that
      influence the risk of serious late complications of pelvic radiation therapy.
      PATIENTS AND METHODS: The records of 3,489 patients treated with radiation
      therapy for International Federation of Gynecology and Obstetrics stage I or II
      carcinoma of the cervix were reviewed for information about patient
      characteristics, treatment details, and outcomes. Any complication occurring or
      persisting more than 3 months after treatment that required hospitalization,
      transfusion, or an operation or caused severe symptoms or the patient's death was
      considered a major late complication. Complication rates were calculated
      actuarially. The median duration of follow-up was 85 months, and 99% of patients
      were followed for at least 3 years or until they died. RESULTS: Heavy smoking was
      the strongest independent predictor of overall complications (multivariate hazard
      ratio, 2.30; 95% confidence interval [CI], 1.84 to 2.87). The most striking
      influence of smoking was on the incidence of small bowel complications (hazard
      ratio for smokers of one or more packs per day, 3.25; 95% CI, 2.21 to 4.78).
      Hispanics had a significantly lower rate of small bowel complications than
      whites, and blacks had higher rates of bladder and rectal complications than
      whites. Thin women had an increased risk of gastrointestinal complications, and
      obese women were more likely to have serious bladder complications. CONCLUSION:
      Complications of pelvic radiation therapy are strongly correlated with smoking,
      race, and other patient characteristics. These factors should be considered
      before the results of clinical studies are generalized to different cultural and
      racial groups.

PMID- 12202667
TI  - Palliative chemotherapy or watchful waiting? A vignettes study among oncologists.
AB  - PURPOSE: To determine the preferences of oncologists for palliative chemotherapy
      or watchful waiting and the factors considered important to that preference.
      METHODS: Sixteen vignettes (paper case descriptions), varying on eight patient
      and treatment characteristics, were designed to assess the oncologists'
      preferences. Their strength of preference was rated on a 7-point scale. An
      orthogonal main effects design provided a subset of all possible combinations of
      the characteristics, allowing estimations of the relative weights of the
      presented characteristics. A written questionnaire was sent to a random sample of
      oncologists (N = 1,235). RESULTS: The response rate was 67%, and 697
      questionnaires were available for analysis. Eighty-one percent of the respondents
      were male. The mean age was 46 years. We found considerable variation among the
      oncologists. No major associations between physician characteristics and
      preferences were found. Of the patient and treatment characteristics affecting
      treatment preference, age was the strongest predictor, followed by the patient's
      wish to be treated and the expected survival gain. Other patient and treatment
      characteristics had a limited effect on preferences, except for psychologic
      distress, which had no independent impact. CONCLUSION: Patients will encounter
      different decisions depending on their oncologists' preferences and their own
      personal background. Therefore, to ensure adequate information for decision
      making processes, decision aids are proposed.

PMID- 12202668
TI  - Prospective exploratory analysis of the association between tumor response,
      quality of life, and expenditures among patients receiving paclitaxel monotherapy
      for refractory metastatic breast cancer.
AB  - PURPOSE: To prospectively evaluate the association between tumor response, change
      in quality of life (QoL), and hospital expenditures in patients with metastatic
      breast cancer (MBC) receiving single-agent paclitaxel. PATIENTS AND METHODS:
      Eligible patients had bidimensionally measurable MBC and any number of previous
      therapies, excluding taxane chemotherapy. Paclitaxel was administered by various
      different infusion schedules. QoL measures were evaluated for each patient at
      baseline and serially using the Memorial Symptom Assessment Scale (MSAS)-Global
      Distress Index (GDI) and Functional Assessment of Cancer Therapy-Breast (FACT-B)
      instruments. Patients were assessed for early (first 6 weeks) and ever changes in
      QoL parameters. Charges were monitored through the hospital's centralized
      computer billing system and converted to cost ratios for the analysis.
      Correlations between response and improvement in QoL were assessed by Fisher's
      exact test statistic. Associations between improvements in QoL with cost ratios
      were assessed by logistic regression and likewise between response and cost
      ratios. RESULTS: Of the 59 patients treated, 50 had sufficient data for
      comparative analyses. The overall response rate was 24% (all partial responses).
      Minor responses were observed in 17% of patients, 25% had stable disease, and 29%
      had progression. Responding patients had significant improvement in QoL as
      assessed by MSAS-GDI (P =.004) and FACT-B (P =.028). The mean total cost/month
      ratios for patients experiencing improved GDI QoL scores was 1.31 versus 1.56 for
      those without QoL benefit (P =.52) and 1.05 versus 1.76 for responders versus
      nonresponders, respectively (P =.07). CONCLUSION: Patients with evidence of tumor
      response on paclitaxel had a QoL benefit not observed in nonresponders, and this
      response was associated with a trend for lower overall costs.

PMID- 12202669
TI  - Communication in end-of-life cancer care: a comparison of team assessments in
      three European countries.
AB  - PURPOSE: To compare team assessments of end-of-life communication in three
      European countries, and to identify factors associated with problematic
      communication. PATIENTS AND METHODS: Three prospective cohort studies used
      similar standardized procedures, and included patients referred to palliative
      care services in the United Kingdom, Ireland, and Italy. Palliative team care
      staff assessed three components of communication in the last week of the
      patient's life-between the patient and family (or those close to them), between
      professionals and patient and family, and between professionals-using a validated
      measure. Univariate and multivariate analyses explored the data and tested for
      relationships between possible explanatory variables and communication. RESULTS:
      Data were collected on 1,326 patients, 416 in the United Kingdom, 411 in Ireland,
      and 499 in Italy. Mean age was 68 years (range, 19 to 95 years), 55% were male,
      and almost two thirds were married. Team members assessed that communication
      between patient and family was a moderate or severe problem in the last week of
      life for 30% to 40% of patients; 10% to 20% had moderate or severe problems
      recorded for the other two communication items. Problematic communication was
      associated with respiratory and breast cancers, a shorter time in care, and
      hospice death. It was also associated with greater spiritual need, need for care
      planning, and poorer patient and family insight (Spearman's rho > 0.4), but not
      especially with pain and symptom control, in both univariate and multivariate
      analyses, both within countries and for all data combined. CONCLUSION: Severe
      communication problems were reported by team assessments in up to 40% of patients
      at the end of life. A multiprofessional approach is needed to recognize and
      improve this.

PMID- 12202670
TI  - Explaining interindividual variability of docetaxel pharmacokinetics and
      pharmacodynamics in Asians through phenotyping and genotyping strategies.
AB  - PURPOSE: To explain the variability of docetaxel pharmacokinetics through study
      of CYP3A phenotype and genotype, and MDR1 genotype. PATIENTS AND METHODS: We
      studied the pharmacokinetics and pharmacodynamics of docetaxel in patients in
      whom it was indicated and who had not received known CYP3A4 substrates. Midazolam
      was administered intravenously to these patients at least 2 days before docetaxel
      treatment, and systemic clearances of both drugs were correlated. Patients were
      characterized for polymorphisms in the CYP3A4 promoter region, CYP3A5, and the
      C3435T polymorphism of MDR1. RESULTS: Thirty-two patients were enrolled, of whom
      31 had full pharmacokinetic data sets. Docetaxel clearance correlated with
      midazolam clearance, body-surface area, serum albumin, and performance status.
      Docetaxel and midazolam clearances were normally distributed. In multiple linear
      regression analyses, midazolam clearance and performance status were the only
      significant covariates of docetaxel clearance, and the area under the curve of
      docetaxel, serum levels of alpha-1-acid glycoprotein, and ALT were significant
      predictors of nadir neutrophil count. No polymorphisms were detected in the 5'
      regulatory region of CYP3A4. Nine patients of 25 studied were homozygous for the
      CYP3A5*3 genotype, and had lower mean clearance of midazolam but not docetaxel.
      The T/T genotype at the C3435T of MDR1, which is associated with reduced P
      glycoprotein function, was found in eight of 27 patients. CONCLUSION: Midazolam
      may be used as a probe drug for CYP3A activity to predict docetaxel clearances,
      hence reducing interindividual variability. Homozygotes for CYP3A5*3 and C3435T
      of MDR1 are common in our population, and their effects on pharmacokinetics of
      relevant substrates should be studied further.

PMID- 12202671
TI  - Molecular biology of anaplastic lymphoma kinase-positive anaplastic large-cell
      lymphoma.
AB  - Anaplastic large-cell lymphoma (ALCL) provides an excellent example of how
      molecular insights into tumor pathogenesis are influencing and improving tumor
      classification. ALCL was described initially as a subtype of T-cell/null-cell
      lymphoma characterized by unusual tumor cell morphology and the expression of
      CD30. However, it was soon recognized that a subset of ALCLs contained
      chromosomal translocations involving anaplastic lymphoma kinase (ALK), a novel
      receptor tyrosine kinase gene. These rearrangements create chimeric genes
      encoding self-associating, constitutively active ALK fusion proteins that
      activate a number of downstream effectors, including phospholipase C-gamma,
      phosphoinositol 3'-kinase, RAS, and signal transducer and activator of
      transcription proteins, all of which seem potentially important in cellular
      transformation. Not all tumors classified as ALCLs have ALK rearrangements and,
      conversely, ALK rearrangements occur in lymphomas of widely varying morphology.
      Hence, only molecular markers can reliably identify ALK+ ALCL. The importance of
      doing so is reflected by clinical studies suggesting that ALK+ ALCLs have a
      significantly better prognosis than other aggressive peripheral T-cell or B-cell
      lymphomas, including ALK- ALCLs. The unique molecular pathogenesis of ALK+ ALCL
      is likely to lead to novel therapeutic approaches directed at specific inhibition
      of ALK or downstream effectors.

PMID- 12202672
TI  - Mechanisms and management of toxicities associated with high-dose interferon alfa
      2b therapy.
AB  - PURPOSE: The toxicity associated with adjuvant high-dose interferon-alfa-2b
      therapy (HDI) for high-risk melanoma can lead to premature discontinuation. It is
      important to understand the expected adverse events and their underlying
      mechanisms and to anticipate and aggressively manage toxicity during treatment in
      order to ensure that patients receive the maximum therapeutic benefit. METHODS:
      The toxicity profile of HDI was reviewed by examining data from the United States
      cooperative group trials. Available published data related to the potential
      mechanisms responsible for the observed adverse events are discussed, and
      comprehensive recommendations for managing side effects are presented. RESULTS:
      The HDI regimen is associated with acute constitutional symptoms, chronic
      fatigue, myelosuppression, elevated liver enzyme levels, and neurologic symptoms.
      The majority of patients tolerate 1 year of therapy with an understanding of the
      anticipated toxicities in conjunction with appropriate dose modifications and
      supportive care. Ongoing monitoring for liver dysfunction and hematologic
      toxicity is critical to ensure safety. Many of the toxicities associated with
      interferon-alfa (IFN-alpha) seem to be the result of endogenous cytokines and
      their effects on the neuroendocrine system. Recent data have also demonstrated
      that IFN-alpha suppresses the activity of specific CYP450 isoenzymes and that
      this correlates with discrete toxicities. Pharmacologic interventions are under
      study for fatigue and depression. An increased understanding of the mechanisms of
      IFN-alpha-associated toxicity will lead to more rational and effective supportive
      care and improved quality of life. CONCLUSION: Continued research in this area
      should lead to improvements in the safety and tolerability of adjuvant therapy
      for melanoma.

PMID- 12202673
TI  - American Society of Clinical Oncology clinical practice guidelines: the role of
      bisphosphonates in multiple myeloma.
AB  - PURPOSE: To determine clinical practice guidelines for the use of bisphosphonates
      in the prevention and treatment of lytic bone disease in multiple myeloma and to
      determine their respective role relative to other conventional therapies for this
      condition. METHODS: An expert multidisciplinary Panel reviewed pertinent
      information from the published literature through January 2002. Values for levels
      of evidence and grade of recommendation were assigned by expert reviewers and
      approved by the Panel. Expert consensus was used if there were insufficient
      published data. The Panel addressed which patients to treat and when to treat
      them in the course of their disease. Additionally, specific drug delivery issues,
      duration of therapy, initiation of treatment and management of treatment of lytic
      bone disease was reviewed and compared with other forms of therapy for lytic bone
      lesions. Finally, the Panel discussed patient and physician expectations
      associated with this therapy for bony metastases, as well as public policy
      implications related to the use of bisphosphonates. The guidelines underwent
      external review by selected physicians, by the Health Services Research Committee
      members, and by the ASCO Board of Directors. RESULTS: The available evidence
      involving randomized controlled trials is modest but supports that oral
      clodronate, intravenous pamidronate, and intravenous zoledronic acid are superior
      to placebo in reducing skeletal complications. A reduction in vertebral fractures
      has consistently been seen across all studies. No agent has shown a definitive
      survival benefit. Intravenous zoledronic acid has recently been shown to be as
      effective as intravenous pamidronate. Because there are no direct comparisons
      between clodronate and pamidronate or zoledronic acid, the superiority of one
      agent cannot be definitively established. However, the panel recommends only
      intravenous pamidronate or zoledronic acid in light of the use of the time to
      first skeletal event as the primary end point and more complete assessment of
      bony complications in studies evaluating it. Additionally, clodronate is not
      available in the United States. The choice between pamidronate and zoledronic
      acid will depend on choosing between the higher drug cost of zoledronic acid,
      with its shorter, more convenient infusion time (15 minutes), versus the less
      expensive drug, pamidronate, with its longer infusion time (2 hours). CONCLUSION:
      Bisphosphonates provide a meaningful supportive benefit to multiple myeloma
      patients with lytic bone disease. However, further research on bisphosphonates is
      warranted, including the following: (1) when to start and stop therapy, (2) how
      to integrate their use with other treatments for lytic bone disease, (3) how to
      evaluate their role in myeloma patients without lytic bone involvement, (4) how
      to distinguish between symptomatic and asymptomatic bony events, and (5) how to
      better determine their cost-benefit consequence.

PMID- 12202674
TI  - Unusual hematologic malignancies. Case 1. Hematologic malignancy presenting with
      diarrhea and bony lesions: systemic mastocytosis.

PMID- 12202675
TI  - Unusual hematologic malignancies. Case 2. Mediastinal germ cell tumor, malignant
      histiocytosis, and acute leukemia.

PMID- 12202676
TI  - Unusual hematologic malignancies. Case 3. CNS involvement in CD56-positive
      intestinal gamma/delta T-cell lymphoma.

PMID- 12202677
TI  - House calls by oncologists: a home-visit primer.

PMID- 12202678
TI  - Reversible pancytopenia caused by oral letrozole assumption in a patient with
      recurrent breast cancer.

PMID- 12202679
TI  - Anastrozole versus tamoxifen as first-line therapy for advanced breast cancer:
      methodologic issues.

PMID- 12202680
TI  - Cost-effectiveness of chemotherapy in non-small-cell lung cancer.

PMID- 12202681
TI  - Eniluracil's need for a targeted approach: a lesson in drug development.

PMID- 12202682
TI  - Estrogen receptor-beta expression in hereditary breast cancer.

PMID- 12202683
TI  - Oxaliplatin: bimonthly, biweekly, or semimonthly? No, fortnightly!

PMID- 12202684
TI  - Signal-driven computations in speech processing.
AB  - Learning a language requires both statistical computations to identify words in
      speech and algebraic-like computations to discover higher level (grammatical)
      structure. Here we show that these computations can be influenced by subtle cues
      in the speech signal. After a short familiarization to a continuous speech
      stream, adult listeners are able to segment it using powerful statistics, but
      they fail to extract the structural regularities included in the stream even when
      the familiarization is greatly extended. With the introduction of subliminal
      segmentation cues, however, these regularities can be rapidly captured.

PMID- 12202686
TI  - Collapse of a degenerate Fermi gas.
AB  - A degenerate gas of identical fermions is brought to collapse by the interaction
      with a Bose-Einstein condensate. We used an atomic mixture of fermionic potassium
      40 and bosonic rubidium-87, in which the strong interspecies attraction leads to
      an instability above a critical number of particles. The observed phenomenon
      suggests a direction for manipulating fermion-fermion interactions on the route
      to superfluidity.

PMID- 12202685
TI  - Macrophage apoptosis by anthrax lethal factor through p38 MAP kinase inhibition.
AB  - The bacterium Bacillus anthracis causes the death of macrophages, which may allow
      it to avoid detection by the innate immune system. We found that B. anthracis
      lethal factor (LF) selectively induces apoptosis of activated macrophages by
      cleaving the amino-terminal extension of mitogen-activated protein kinase (MAPK)
      kinases (MKKs) that activate p38 MAPKs. Because macrophages that are deficient in
      transcription factor nuclear factor kappaB (NF-kappaB) are also sensitive to
      activation-induced death and p38 is required for expression of certain NF-kappaB
      target genes, p38 is probably essential for synergistic induction of those NF
      kappaB target genes that prevent apoptosis of activated macrophages. This
      dismantling of the p38 MAPK module represents a strategy used by B. anthracis to
      paralyze host innate immunity.

PMID- 12202687
TI  - Progress at the National Institute of Biomedical Imaging and Bioengineering.

PMID- 12202688
TI  - Diagnosis Please Certificate of Recognition awarded to four individuals.

PMID- 12202690
TI  - The impact of MR imaging in sports medicine.
AB  - Sports medicine is one of the most rapidly growing subspecialties in orthopedics.
      Magnetic resonance (MR) imaging in sports medicine includes depiction of normal
      anatomy and pathologic conditions in almost every joint in the body, but the MR
      examinations most frequently requested are of the knee and shoulder. The reported
      high accuracy of MR imaging in the knee has resulted in MR imaging being
      preferred to diagnostic arthroscopy by most leading orthopedic surgeons. MR
      imaging is particularly helpful for sports medicine surgeons in evaluating
      menisci to determine if they are repairable, in posterolateral corner syndrome,
      and in evaluating the hyaline articular cartilage. In evaluating the shoulder, MR
      arthrography is becoming the preoperative imaging procedure of choice for many
      sports medicine surgeons. Shoulder MR imaging is particularly important in
      helping identify abnormalities that may mimic rotator cuff or labral
      abnormalities at clinical examination, thus preventing unnecessary surgery in
      some patients. These abnormalities include Parsonage-Turner syndrome and
      quadrilateral space syndrome, each of which has a distinctive MR imaging
      appearance. As the field of sports medicine expands, radiologists will continue
      to see increased requests for MR imaging, because sports medicine and high
      quality imaging are inextricably linked.

PMID- 12202691
TI  - Current clinical trials of the american college of radiology imaging network.

PMID- 12202692
TI  - Terminology of hepatocellular nodules in cirrhosis: plea for consistency.

PMID- 12202693
TI  - The importance of strategy for the evolving field of radiology.
AB  - During the 20th century, the field of radiology experienced extraordinary growth
      and became an essential component of the practice of clinical medicine. In the
      21st century, it is likely that radiology will continue to grow by interfacing
      with new and important domains such as information technology and molecular
      biology and by playing a more central role in general medical education,
      biomedical research, and noninvasive therapeutic interventions. To sustain such
      wide-ranging growth and yet remain intact as a medical specialty, the profession
      will require many radiologists who can provide leadership to bridge the many gaps
      between the various frontiers and the traditional core of radiology. These
      radiologists will need skills and background in two critical management areas:
      leadership and strategy. This article approaches the broad topic of strategy in
      several ways. First, it provides the radiologist with a basic framework for
      strategy development. Second, it summarizes central ideas from the evolving field
      of strategic thinking. Finally, it outlines a strategy-based method for dealing
      with uncertainty about the future and identifies situations where specific
      strategic tools and techniques are likely to be helpful.

PMID- 12202694
TI  - Pedal abscesses in patients suspected of having pedal osteomyelitis: analysis
      with MR imaging.
AB  - PURPOSE: To document the expected frequency, location, and size of pedal
      abscesses in patients with advanced foot infection. MATERIALS AND METHODS: Images
      obtained at contrast material-enhanced magnetic resonance (MR) imaging (at 1.5 T)
      of 161 feet of 51 women and 107 men (mean age, 58.5 years; 82.3% had diabetes)
      who underwent bone biopsy after MR imaging for possible osteomyelitis were
      reviewed by two musculoskeletal radiologists working together. Presence, size,
      and location of abscesses and presence of adjacent skin ulceration were noted. MR
      imaging criteria for abscess were the following: presence of fluid collection
      with isointense or hypointense signal on T1-weighted images, fluid-equivalent
      signal intensity on T2-weighted images, and peripheral rim enhancement. All
      patients' charts were reviewed for clinical and surgical information. RESULTS:
      Thirty-two fluid collections compatible with abscesses were found in 29 (18.4%)
      of the 158 patients; 26 (90%) of these patients had diabetes (P =.38). Abscess
      size varied from 1 x 0.5 x 0.4 cm to 3.8 x 3.4 x 2.2 cm (mean = 2.6 x 1.5 x 0.9
      cm). Abscesses were located in the forefoot (n = 15), hindfoot (n = 7), toes (n =
      3), midfoot (n = 4), or in multiple locations (n = 3). Thirty-one abscesses (97%)
      occurred near a skin ulcer (distance range, 0-9.1 cm; mean, 1.4 cm). Abscesses
      were significantly more frequent in patients with osteomyelitis (n = 28, 97%) (P
      <.001) and in feet that had been treated surgically (n = 16, 33%) (P <.002).
      CONCLUSION: MR imaging revealed abscesses, predominantly in the forefoot, in 18%
      of patients suspected of having pedal osteomyelitis. Abscesses are significantly
      more frequent in patients with osteomyelitis and in feet that have been treated
      surgically.

PMID- 12202695
TI  - Water excitation as an alternative to fat saturation in MR imaging: preliminary
      results in musculoskeletal imaging.
AB  - PURPOSE: To compare fat suppression methods by using spectrally selective fat
      saturation and section-selective water excitation in standard magnetic resonance
      (MR) imaging sequences used in day-to-day musculoskeletal practice. MATERIALS AND
      METHODS: Eighty-three patients underwent MR examination with a 1.5-T system. The
      two methods were compared by using three common sequences: T1-weighted spin-echo
      (SE) imaging performed after contrast material injection (n = 24), intermediate
      weighted fast SE (n = 36) imaging, and T2-weighted fast SE (n = 36) imaging.
      Acquisition times of the sequences and signal-to-noise and contrast-to-noise
      ratios of bone, muscle, fat, and water for the two methods were compared
      quantitatively. Images were then qualitatively reviewed by two radiologists who
      were blinded to the type of fat suppression used. Image quality was scored
      according to four criteria (homogeneity of fat suppression, susceptibility and
      foldover artifacts, conspicuousness of lesion, and overall image quality) by
      using a five-point scale (0, bad; 1, poor; 2, fair; 3, good; and 4, excellent). A
      paired Student t test was used to compare the quantitative data, and a
      nonparametric paired-data Wilcoxon signed rank test was used for qualitative
      analysis. RESULTS: Water excitation allowed a substantial decrease in acquisition
      time (by up to 50%) for T1-weighted sequences. Quantitative measurements revealed
      a greater signal-to-noise ratio (P <.01) with water excitation for all three
      sequences, whereas the contrast-to-noise ratio was greater with water excitation
      only in intermediate-weighted sequences (P <.01). Qualitatively, water excitation
      proved statistically better than or equal to fat saturation for all criteria in
      all imaging sequences (P <.05). Mean scores of overall image quality ranged
      between 2.5 and 3.0 for fat saturation and 3.4 and 3.7 for water excitation,
      respectively (P <.05). CONCLUSION: Section-selective water excitation is faster
      than conventional fat saturation and produces images of better quality.

PMID- 12202697
TI  - Diagnosis please. Case 50: primary coccidioidal synovitis of the knee.

PMID- 12202698
TI  - Posterior distal femoral and proximal tibial metaphyseal stripes at MR imaging in
      children and young adults.
AB  - PURPOSE: To determine the frequency and distribution of the hyperintense stripe
      seen along the posterior surface of distal femoral and proximal tibial metaphyses
      at magnetic resonance (MR) imaging. MATERIALS AND METHODS: One hundred forty-two
      MR imaging studies obtained in 139 children and young adults were reviewed. The
      authors recorded the presence and distribution of posterior distal femoral and
      proximal tibial metaphyseal stripes. Presence of stripe was correlated with
      patient age and sex and with patency of the adjacent physis. Fifty-nine studies
      of adults were reviewed similarly. Two-way analysis of variance was performed to
      compare mean patient age for sex among four different categories that were based
      on stripe presence and physeal patency. Orthogonal contrasts were used to
      determine whether a linear trend across the categories existed. In one cadaveric
      femur, imaging and histologic analysis were performed. RESULTS: A metaphyseal
      stripe was seen in all patients with a completely or partially open physis (110
      femora, 102 tibiae) and in 56 femora and 60 tibiae in the patients with fused
      physes. Thirty-five femora and 35 tibiae showed no stripe; all patients were
      skeletally mature. Correlations between metaphyseal stripe visualization and
      physeal patency were significant (P <.001). Differences in mean patient age among
      the four categories were significant for both (femoral and tibial) locations (P
      <.001), and a linear trend with age (P <.001) was demonstrated. This linear trend
      was also observed in both sexes (P <.001). Histologic analysis revealed highly
      vascular loose fibrous tissue. CONCLUSION: A posterior metaphyseal stripe is seen
      at MR imaging of the skeletally immature knee and likely reflects normal bone
      growth.

PMID- 12202699
TI  - Idiopathic chronic pancreatitis in children: MR cholangiopancreatography after
      secretin administration.
AB  - PURPOSE: To assess the accuracy of dynamic magnetic resonance (MR)
      cholangiopancreatography after secretin administration in detecting pancreatic
      duct abnormalities typical of early-onset idiopathic chronic pancreatitis in
      children with recurrent episodes of idiopathic acute pancreatitis. MATERIALS AND
      METHODS: Fifteen children (mean age, 11.3 years; range, 6-17 years) with at least
      three recurrent episodes of idiopathic acute pancreatitis prospectively underwent
      MR cholangiopancreatography before and after secretin administration. Image
      analysis included visualization of side branches, ductal narrowing, endoluminal
      filling defects, irregular ductal contour, cavities, and pancreas divisum. All
      patients underwent endoscopic retrograde cholangiopancreatography (ERCP).
      RESULTS: Dilated side branches were detected in three (20%) of 15 patients on MR
      cholangiopancreatograms obtained before secretin administration and in seven
      (47%) of 15 patients on images obtained after secretin administration. Ductal
      narrowing was detected in one (7%) of 15 patients on images obtained before
      secretin administration and in two (13%) of 15 patients on images obtained after
      secretin administration. Endoluminal filling defects in one (7%) of 15 patients
      were observed on MR cholangiopancreatograms obtained both before and after
      secretin administration. Irregular contour of the main pancreatic duct was
      present in four (27%) of 15 patients on MR cholangiopancreatograms obtained
      before secretin administration and in five (33%) of 15 patients on images
      obtained after secretin administration. Cavities and pancreas divisum were
      detected in one (7%) of 15 patients and in two (13%) of 15 patients,
      respectively, only on MR cholangiopancreatograms obtained after secretin
      administration. CONCLUSION: Secretin improves the sensitivity of MR
      cholangiopancreatography in diagnosing early-onset idiopathic chronic
      pancreatitis.

PMID- 12202700
TI  - Functional and morphologic evaluation of congenital urinary tract dilatation by
      using combined static-dynamic MR urography: findings in kidneys with a single
      collecting system.
AB  - PURPOSE: To assess combined static-dynamic magnetic resonance (MR) urography in
      the evaluation of congenital urinary tract dilatation in infants and children.
      MATERIALS AND METHODS: Sixty-two patients with urinary tract dilatation underwent
      prospective examination with combined static-dynamic MR urography. A combination
      examination involved use of a static T2-weighted three-dimensional inversion
      recovery fast spin-echo sequence and a dynamic T1-weighted two-dimensional fast
      field-echo sequence with gadopentetate dimeglumine-DTPA and furosemide
      application. Twelve additional patients underwent examination with only static MR
      urography. Thus, both image quality and morphologic features were assessed in 74
      patients with the use of MR urography. The results were compared with those of
      ultrasonography and, when available, conventional urography or surgery. In 62
      patients, the dynamic sequence was used to calculate split renal function from
      renograms generated from parenchymal regions of interest and to assess urinary
      excretion from whole-kidney renograms. Results were compared with those of
      diuretic renal scintigraphy (DRS) for split function (Spearman rank correlation
      coefficient) and urinary excretion (kappa coefficient). RESULTS: Stenoses at the
      ureteropelvic (n = 33) and ureterovesical (n = 31) junctions and within the
      ureter (n = 3) and nonstenotic dilatation (n = 23) were clearly depicted, while
      the normal urinary tract (n = 51) was depicted in its entirety in 47 of 51
      examinations. Image quality was considered good or excellent in 95% of the kidney
      ureter units. For split renal function, dynamic MR urography and DRS showed
      significant correlation (r = 0.92, P <.001). For urinary excretion, MR urography
      and DRS showed strong agreement (kappa = 0.67), with concordant classification of
      urinary excretion in 59 (81%) of 73 abnormal kidney-ureter units and in all 47
      (100%) normal kidney-ureter units. CONCLUSION: Combined static-dynamic MR
      urography provides high-quality depiction of the urinary tract in infants and
      children, while allowing accurate determination of single-kidney function and
      reliable evaluation of urinary excretion.

PMID- 12202701
TI  - Renal masses: quantitative assessment of enhancement with dynamic MR imaging.
AB  - PURPOSE: To establish a quantitative magnetic resonance (MR) imaging contrast
      enhancement criterion for distinguishing cysts from solid renal lesions.
      MATERIALS AND METHODS: Regions of interest were measured in 74 patients with
      renal lesions evaluated by means of dynamic contrast material-enhanced MR imaging
      with serial breath-hold spoiled gradient-echo acquisitions. Sensitivity for renal
      tumors and specificity for renal cysts were established by using percentage of
      enhancement thresholds that varied between 5% and 35%. RESULTS: The mean
      percentage of enhancement at MR imaging for the 50 renal cysts was less than 5%;
      for the 50 renal tumors, it was 97% or higher. With use of a threshold percentage
      of enhancement of 15% and results obtained between 2 and 4 minutes after
      administration of contrast material, all malignancies (sensitivity for tumor,
      100%) were diagnosed, and there were 6% or fewer false-positive tumor diagnoses.
      Lower thresholds resulted in unacceptably high false-positive rates (ie, cysts
      that appeared to enhance-pseudoenhancement), whereas higher threshold values
      (>20%) resulted in an unacceptably lower sensitivity for tumors. CONCLUSION: The
      optimal percentage of enhancement threshold for distinguishing cysts from
      malignancies with the imaging technique prescribed was 15%, and the optimal
      timing for measurement was 2-4 minutes after administration of contrast material.

PMID- 12202702
TI  - Patients with a history of elevated prostate-specific antigen levels and negative
      transrectal US-guided quadrant or sextant biopsy results: value of MR imaging.
AB  - PURPOSE: To determine the role of magnetic resonance (MR) imaging performed with
      a combined endorectal body phased-array coil for patients with elevated prostate
      specific antigen (PSA) levels or suspicious free-to-total PSA ratios in whom
      prior transrectal ultrasonographically (US) guided biopsy findings were negative
      for prostate cancer. MATERIALS AND METHODS: Forty-four patients with PSA levels
      greater than 4 ng/mL or free-to-total PSA ratios lower than 15% but negative
      biopsy findings were examined with T1- and T2-weighted MR imaging at 1.5 T with a
      combined endorectal body phased-array coil. All patients underwent digital rectal
      examination (DRE) and transrectal US. Thirty-eight patients underwent repeat
      biopsy after MR imaging. The accuracy of MR imaging for detection of prostate
      cancer was assessed prospectively. Retrospectively, MR imaging findings were
      correlated with individual biopsy site findings. MR imaging and biopsy results
      were correlated by using a cross table to calculate sensitivity, specificity, and
      positive predictive value (PPV). Retrospective analysis results were evaluated
      with receiver operating characteristic analysis. A P value of less than.05
      indicated significance (chi(2) test according to Pearson). RESULTS: At
      prospective analysis, MR imaging had a sensitivity of 83% and a PPV of 50% for
      detection of prostate cancer; these values were 33% and 67%, respectively, for
      DRE and 33% and 57%, respectively, for transrectal US. At retrospective site-by
      site analysis, MR imaging results did not correlate significantly with individual
      biopsy site findings (P =.126); sensitivity was 65% and PPV was 12%. CONCLUSION:
      In this patient population, MR imaging has higher sensitivity for detection of
      prostate cancer than DRE or transrectal US.

PMID- 12202703
TI  - Angiographic classification of ovarian artery-to-uterine artery anastomoses:
      initial observations in uterine fibroid embolization.
AB  - PURPOSE: To prospectively study and classify the anastomoses between the ovarian
      and uterine arteries in women undergoing uterine fibroid embolization, and to
      compare the presence of such with procedural failures and premature menopause.
      MATERIALS AND METHODS: Angiographic ovarian artery-to-uterine artery anastomoses
      were studied in 76 consecutive patients undergoing uterine fibroid embolization.
      Mean patient age was 44.7 years (range, 29-56 years). Clinical follow-up
      consisted of a standard questionnaire. Procedural failure and complications were
      compared with the presence of various types of ovarian artery-to-uterine artery
      connections. RESULTS: Three types of anastomoses were identified. In type I (33
      [21.7%] of 152 arteries), flow from the ovarian artery to the uterus was through
      anastomoses with the main uterine artery. In type II (six arteries [3.9%]), the
      ovarian artery supplied the fibroids directly. In type III (10 arteries [6.6%]),
      the major blood supply to the ovary was from the uterine artery. Seven patients
      (9%) were considered to have clinical failure, with three of the six women with
      type II anastomoses being in this group. Three of the five women who experienced
      menopause after fibroid embolization had bilateral ovarian artery-to-uterine
      artery anastomoses that were classified as high risk. CONCLUSION: Delineation of
      ovarian artery-to-uterine artery anastomosis is of practical relevance in
      avoiding nontarget ovarian embolization, in identification of those who would be
      at risk of uterine artery embolization or ovarian failure, and in those in whom
      the ovarian artery can be embolized safely.

PMID- 12202704
TI  - Amyotrophic lateral sclerosis: enteral nutrition provision--endoscopic or
      radiologic gastrostomy?
AB  - PURPOSE: To retrospectively evaluate gastrostomy placement in patients with
      amyotrophic lateral sclerosis (ALS) to determine the insertion method of choice.
      MATERIALS AND METHODS: During 3(1/2) years, 36 patients with ALS (19 men, 17
      women; mean age, 54 years; age range, 37-69 years) underwent gastrostomy. Twenty
      patients were primarily referred for percutaneous endoscopic gastrostomy (PEG)
      and 16 for percutaneous radiologic gastrostomy (PRG). Gastrostomy method, success
      rate of each technique, and reason for procedure failure were reviewed in each
      patient. Forced vital capacity (FVC) prior to gastrostomy was recorded. PEG was
      performed with a pull-through technique after transillumination of the abdominal
      wall. PRG was performed with fluoroscopic guidance and T-fastener gastropexy. A
      log-rank test was used to compare survival rates after PRG and PEG, and a
      Wilcoxon rank sum test was used to evaluate the influence of declining FVC on PEG
      success. The Kaplan-Meier product limit method was used to estimate survival
      probabilities. RESULTS: Of the 20 patients referred for PEG, 11 had successful
      results. The nine failures (45%) resulted from failure to transilluminate the
      abdominal wall. All 16 patients primarily referred for PRG underwent successful
      gastrostomy. The nine patients in whom PEG failed underwent subsequent successful
      PRG. In patients with diaphragmatic palsy and a high subcostal stomach, an angled
      subcostal approach (n = 6) or intercostal approach (n = 2) was required at PRG.
      One death occurred in the PEG group (9%) because of procedure-related aspiration,
      and a second patient from the PEG group required laparotomy for postprocedural
      peritonitis. One death occurred in the PRG group (4%) because of inadvertent
      placement of the feeding tube in the peritoneal cavity. There was no significant
      difference between PEG and PRG in patient survival. FVC did not have a
      statistically significant influence on PEG failure. CONCLUSION: Results show PRG
      to be the method of choice.

PMID- 12202705
TI  - Balloon dilation for achalasia of the cardia: experience in 76 patients.
AB  - PURPOSE: To report our experience with balloon dilation for achalasia of the
      cardia. MATERIALS AND METHODS: Seventy-six patients (mean age, 51 years)
      underwent balloon dilation with radiologic guidance. A total of 110 procedures
      were performed from April 1994 to April 2000. Diagnosis of achalasia was
      established with clinical, radiologic, and manometric data. Dysphagia was a
      presenting symptom in most patients (90%), regurgitation was present in 39%,
      retrosternal pain in 22%, and weight loss in 12%. The dilations were performed in
      a progressive manner starting with a 15-mm-diameter balloon and progressing to 20
      , 30-, and 40-mm balloons, as required. Follow-up data were collected
      retrospectively from patient notes and telephone interviews with the patients
      and/or their local doctors (mean follow-up, 26 months). RESULTS: There were no
      cases of esophageal perforation; 89% (98 of 110) of dilations were considered to
      be successful, with the patients having restoration of normal or near-normal
      swallowing (excellent or good initial responses). Fifty-two patients required a
      single dilation; 22 patients, between two and four dilations; and two patients,
      five dilations. CONCLUSION: Balloon dilation with fluoroscopic guidance is a safe
      and successful treatment for achalasia of the cardia.

PMID- 12202706
TI  - Bile duct: analysis of percutaneous transluminal forceps biopsy in 130 patients
      suspected of having malignant biliary obstruction.
AB  - PURPOSE: To evaluate percutaneous transluminal forceps biopsy in patients
      suspected of having a malignant biliary obstruction. MATERIALS AND METHODS: One
      hundred thirty consecutive patients (82 men and 48 women; mean age, 59 years)
      with obstructive jaundice underwent transluminal forceps biopsy during or after
      percutaneous transhepatic biliary drainage. The lesions involved the common bile
      duct (n = 58), common hepatic duct (n = 39), hilum (n = 14), ampullary segment of
      the common bile duct (n = 11), right or left intrahepatic bile duct (n = 5), or
      the entire extrahepatic bile duct (n = 3). In each patient, three to five
      specimens (mean, 4.1 specimens) were taken from the lesion with 5.4-F biopsy
      forceps. The final diagnosis for each patient was confirmed with pathologic
      findings at surgery, additional histocytologic data, or clinical and radiologic
      follow-up. Statistical analysis was performed with the chi(2) test; a P value <
      or =.05 was considered to indicate a significant difference. RESULTS: Ninety
      eight of 130 biopsies resulted in correct diagnoses of malignancy. Five biopsy
      diagnoses proved to be true-negative. There were 27 false-negative diagnoses and
      no false-positive diagnoses. The diagnostic performance of transluminal forceps
      biopsy in malignant biliary obstructions was as follows: sensitivity, 78.4%;
      specificity, 100%; and accuracy, 79.2%. Sensitivity of biopsy in the 82 patients
      with cholangiocarcinoma was higher than in the 43 patients with malignant tumors
      other than cholangiocarcinoma (86.6% vs 62.8%, P <.005). Sensitivity was
      significantly lower in the ampullary segment of the common bile duct than in
      other sites (P <.01). No major complications related to the biopsy procedures
      occurred. CONCLUSION: Percutaneous transluminal forceps biopsy is a safe
      procedure that is easy to perform through a transhepatic biliary drainage tract.
      It provides relatively high accuracy in the diagnosis of malignant biliary
      obstructions.

PMID- 12202707
TI  - Long-term results 10 years after iliac arterial stent placement.
AB  - PURPOSE: To retrospectively evaluate results in 110 patients who had iliac
      arterial occlusive disease and were treated with stents before 1991. MATERIALS
      AND METHODS: From 1987 to 1990, 110 patients (mean age, 57 years) with iliac
      arterial occlusive disease (Fontaine stage IIa, seven patients; IIb, 95 patients;
      III, four patients; IV, four patients) underwent implantation of a self-expanding
      metal stent. Stenoses (n = 66) were treated after failed angioplasty, and
      occlusions (n = 60) were treated with primary stent placement. Follow-up included
      angiography and/or color duplex ultrasonography and clinical examination with
      ankle-brachial index measurement. Patients lost to follow-up were interviewed by
      using dedicated questionnaires administered by telephone and/or mail. If a
      patient was deceased, relatives and attending doctors were interviewed. RESULTS:
      The fate of 109 of the 110 patients was determined. Overall, 46 patients died: 18
      within 5 years, 39 within 10 years, and seven after more than 10 years. The 5-
      and 10-year survival rates were 83% and 64%, respectively. Cardiovascular disease
      caused 23 deaths; malignant tumor caused 15. The cause of death remained unknown
      in five patients. Primary stent patency rates were 66% +/- 4.8 (standard error)
      after 5 years and 46% +/- 5.9 after 10 years; secondary patency rates were 79% +/
      4.2 after 5 years and 55% +/- 6.3 after 10 years (Kaplan-Meier test). Seventeen
      (16%) patients underwent surgical bypass of the aortoiliac arteries that involved
      the segment with the stent, 14 because of stent restenosis and three because of
      stenosis in other iliac arterial segments. CONCLUSION: The main cause of death in
      patients with intermittent claudication was cardiac disease. Long-term patency of
      iliac arterial stents was moderate.

PMID- 12202708
TI  - Elective endovascular versus open surgical repair of abdominal aortic aneurysms:
      systematic review of short-term results.
AB  - PURPOSE: To summarize and compare published short-term results of elective
      endovascular and open surgical repair of abdominal aortic aneurysms. MATERIALS
      AND METHODS: A MEDLINE search of the English literature was performed. Studies
      with at least 10 patients in each treatment group were included if they reported
      patient characteristics, complications, and mortality. Two reviewers
      independently extracted the data. A random-effects model was used to pool the
      data and calculate pooled odds ratios (endovascular vs open surgical repair).
      RESULTS: Nine studies were included, reporting results of 1,318 procedures (687
      endovascular repair and 631 open surgical repair). Mean blood loss was 456 mL for
      endovascular repair and 1,202 mL for open surgical repair (P =.003). On average,
      patients undergoing endovascular repair spent 0.5 days in the intensive care unit
      and 3.9 days in the hospital, and patients undergoing open surgical repair spent
      2.2 days (P =.04) in the intensive care unit and 10.3 days (P =.02) in the
      hospital. The pooled 30-day-mortality was 0.03 for endovascular repair (95% CI:
      0.02, 0.04) and 0.04 for open surgical repair (95% CI: 0.00, 0.07) (P =.03), and
      the odds ratio was 0.55 (95% CI: 0.33, 0.92). The pooled local and/or vascular
      complication rate was 0.16 for endovascular repair (95% CI: 0.06, 0.25) and 0.12
      for open surgical repair (95% CI: 0.06, 0.18) (P =.46), and the odds ratio was
      0.97 (95% CI: 0.62, 1.54). The pooled systemic and/or remote complication rate
      was 0.17 for endovascular repair (95% CI: 0.09, 0.25) and 0.44 for open surgical
      repair (95% CI: 0.21, 0.66) (P <.001), and the odds ratio was 0.22 (95% CI: 0.11,
      0.45). CONCLUSION: On the basis of this systematic review, endovascular repair
      results in less blood loss, shorter intensive care unit and hospital stays, lower
      30-day mortality, and lower systemic and/or remote complication rates than those
      of open surgical repair.

PMID- 12202709
TI  - Detection of hepatic metastases from cancers of the gastrointestinal tract by
      using noninvasive imaging methods (US, CT, MR imaging, PET): a meta-analysis.
AB  - PURPOSE: To perform a meta-analysis to compare current noninvasive imaging
      methods (ultrasonography [US], computed tomography [CT], magnetic resonance [MR]
      imaging, and (18)F fluorodeoxyglucose [FDG] positron emission tomography [PET])
      in the detection of hepatic metastases from colorectal, gastric, and esophageal
      cancers. MATERIALS AND METHODS: A MEDLINE literature search and review of article
      bibliographies and our institutional charts of patients with colorectal cancer
      identified data with histopathologic correlation or at least 6 months of patient
      follow-up. Two authors independently abstracted data sets and excluded data
      without contingency tables or data published more than once. Summary-weighted
      estimates of sensitivity were obtained and stratified according to specificity of
      less than 85% or 85% and higher. A covariate analysis was used to evaluate the
      influence of patient- or study-related factors on sensitivity. RESULTS: Among 111
      data sets, nine US (509 patients), 25 CT (1,747 patients), 11 MR imaging (401
      patients), and nine PET (423 patients) data sets met the inclusion criteria. In
      studies with a specificity higher than 85%, the mean weighted sensitivity was 55%
      (95% CI: 41, 68) for US, 72% (95% CI: 63, 80) for CT, 76% (95% CI: 57, 91) for MR
      imaging, and 90% (95% CI: 80, 97) for FDG PET. Results of pairwise comparison
      between imaging modalities demonstrated a greater sensitivity of FDG PET than US
      (P =.001), CT (P =.017), and MR imaging (P =.055). CONCLUSION: At equivalent
      specificity, FDG PET is the most sensitive noninvasive imaging modality for the
      diagnosis of hepatic metastases from colorectal, gastric, and esophageal cancers.

PMID- 12202710
TI  - Aortic and hepatic enhancement and tumor-to-liver contrast: analysis of the
      effect of different concentrations of contrast material at multi-detector row
      helical CT.
AB  - PURPOSE: To investigate the effect of different iodine concentrations of contrast
      material on aortic and hepatic enhancement and the detectability of hypervascular
      hepatocellular carcinoma (HCC) with multi-detector row computed tomography (CT)
      and a uniphasic contrast material injection technique. MATERIALS AND METHODS: Two
      hundred one patients with known or who were suspected of having HCC underwent
      multi-detector row CT; 58 patients with hypervascular HCC were identified. First
      , second-, and third-phase scanning was started with the aortic arrival times
      plus 15 seconds, plus 30 seconds, and plus 105 seconds, respectively. All
      patients were assigned randomly into two groups. Patients in groups A and B
      received iopamidol with an iodine concentration of 300 mg/mL and 370 mg/mL,
      respectively, with the same total iodine load per patient per body weight. The
      liver and aorta enhancement and tumor-to-liver contrast (TLC) were measured.
      Depiction of hepatic arteries was evaluated visually by two radiologists.
      RESULTS: During the first phase, aortic enhancement was significantly (P <.01)
      higher in group B, with no significant difference in hepatic enhancement between
      the two groups. During the second phase, aortic enhancement was significantly (P
      <.01) higher in group A, with no significant difference in hepatic enhancement.
      The TLC was significantly (P <.01) higher in group B during the first phase, but
      there was no significant difference between the two groups during the second
      phase. There was no significant difference in any parameters between the two
      groups during the third phase. Depiction of the hepatic arteries in group B was
      significantly (P <.05) superior to that in group A. CONCLUSION: In the arterial
      phase, administration of a higher concentration of contrast material is effective
      for a significantly higher TLC.

PMID- 12202711
TI  - Isoattenuating pancreatic adenocarcinoma at multi-detector row CT: secondary
      signs.
AB  - PURPOSE: To assess the frequency of isoattenuating pancreatic adenocarcinoma with
      multi-detector row computed tomography (CT) and determine whether there are
      specific secondary signs that aid in detection. MATERIALS AND METHODS: Fifty
      three patients with pancreatic adenocarcinoma underwent contrast material
      enhanced biphasic multi-detector row CT with curved planar reformation. Tumors
      were initially deemed isoattenuating or hypoattenuating to normal pancreatic
      parenchyma on the basis of visual inspection, and the degree of attenuation was
      confirmed by calculating the mean attenuation differences between normal
      pancreatic parenchyma and tumor (tumor-pancreas contrast) during the pancreatic
      phase. Indirect signs of pancreatic tumor were tabulated in patients with an
      isoattenuating tumor. RESULTS: Of the 53 patients, six (11%) had isoattenuating
      tumors with a mean tumor-pancreas contrast of 9.25 HU +/- 11.3 during the
      pancreatic phase and 4.15 HU +/- 8.5 during the portal venous phase. The
      secondary signs of pancreatic tumor in these six patients included an interrupted
      pancreatic duct (n = 5), dilated biliary and pancreatic ducts (n = 1), atrophic
      distal pancreatic parenchyma (n = 3), and mass effect and/or convex contour
      abnormality (n = 3). The mean tumor-pancreas contrast for the remaining 47
      patients was 74.76 HU +/- 35.61 during the pancreatic phase. CONCLUSION: With no
      visible tumor-pancreas contrast for isoattenuating tumors, indirect signs such as
      mass effect, atrophic distal parenchyma, and an interrupted duct sign are
      important indicators for the presence of tumor.

PMID- 12202712
TI  - Cirrhosis: modified caudate-right lobe ratio.
AB  - PURPOSE: To determine whether a modified caudate-right lobe ratio (C/RL) with use
      of the right portal vein to set the lateral boundary (C/RL-r) is more accurate
      for diagnosing cirrhosis and evaluating its clinical severity than is the
      previously described C/RL with use of the main portal vein to set the lateral
      boundary (C/RL-m). MATERIALS AND METHODS: Two hundred thirty-six patients (121
      with pathologically proved cirrhosis and 115 without history of chronic hepatic
      diseases) underwent magnetic resonance (MR) imaging. Two independent observers
      measured C/RL-r and compared it with C/RL-m. Results were compared by using
      receiver operating characteristic (ROC) curves and accuracy measures at various
      thresholds. RESULTS: The area below the ROC curve was greater for C/RL-r (0.797)
      than for C/RL-m (0.731; P =.040). By using a C/RL-r greater than 0.90, the
      sensitivity, specificity, and accuracy for the MR imaging diagnosis of cirrhosis
      were 71.7%, 77.4%, and 74.2%, respectively. The highest accuracy of the C/RL-m
      was 65.7%, when the C/RL-m was greater than 0.55. Interobserver agreement was
      statistically confirmed for both measurements by using kappa analysis.
      Significant differences were found among the three Child-Pugh classes by using
      C/RL-r (P =.0105) but not by using C/RL-m. CONCLUSION: C/RL-r is more accurate
      for diagnosing cirrhosis and evaluating its clinical severity than is C/RL-m.

PMID- 12202713
TI  - Primary neoplasms of the appendix manifesting as acute appendicitis: CT findings
      with pathologic comparison.
AB  - PURPOSE: To evaluate the computed tomographic (CT) findings in patients with
      acute appendicitis related to an underlying appendiceal neoplasm. MATERIALS AND
      METHODS: Clinical and pathologic data obtained over a 10-year period in 65
      patients with primary appendiceal neoplasms were reviewed. Preoperative CT
      studies in patients who presented clinically with symptoms of acute appendicitis
      were analyzed retrospectively and in consensus by three radiologists. The
      appendix was evaluated on CT scans for morphology, location, presence of
      calcification, maximal diameter, and wall thickness. RESULTS: Twenty-six (40%) of
      the 65 patients with appendiceal neoplasms had presented with symptoms of acute
      appendicitis. Preoperative CT studies available in 22 patients showed increased
      appendiceal diameter, wall thickening, and periappendiceal fat stranding in 22
      (100%), 22 (100%), and 21 (95%) patients, respectively. The appendiceal diameter
      was greater than 15 mm (mean diameter, 2.9 cm) in 19 patients (86%). Morphologic
      changes of concern for neoplasm were present in 19 patients (86%) and included
      cystic dilatation in nine patients and presence of a soft-tissue mass without
      dilatation in 10 patients. An appendiceal diameter greater than 15 mm and/or a
      morphologic abnormality were present in 21 of 22 cases (95%). CONCLUSION: CT
      findings strongly suggest the presence of underlying neoplasm in the majority of
      patients with secondary appendicitis.

PMID- 12202714
TI  - Incidental colonic fluorodeoxyglucose uptake: correlation with colonoscopic and
      histopathologic findings.
AB  - PURPOSE: To evaluate the pattern and degree of incidental colonic
      fluorodeoxyglucose (FDG) uptake in patients without colorectal carcinoma who
      underwent whole-body FDG positron emission tomography (PET) for other purposes
      and compare them with colonoscopic and/or histopathologic findings. MATERIALS AND
      METHODS: Cases of 27 patients without known history of colorectal carcinoma who
      were referred for evaluation with whole-body FDG PET and displayed incidental
      colonic uptake were reviewed retrospectively. Colonoscopy was performed in 10
      patients; histopathologic analysis, in two; and both, in 15. The colonic FDG
      uptake patterns were nodular-focal, nodular-multifocal, segmental, and diffuse.
      The FDG uptake level was scored with a four-point scale in relation to hepatic
      uptake. Binomial distribution was used to calculate 95% CIs for the probability
      of finding an abnormality at histologic examination, as predicted by findings at
      FDG PET. RESULTS: Colonoscopic findings in eight patients with a diffuse uptake
      pattern were normal. Thirteen patients with nodular high FDG uptake had
      pathologic findings. Six (22%) of the 27 patients were not suspected of having a
      malignancy, and seven had benign neoplasms. With a 95% CI, nodular high FDG
      uptake implies at least a 79% chance that histopathologic findings may be
      abnormal. Colitis was seen in five of six patients with a segmental pattern of
      high FDG uptake. CONCLUSION: Colonoscopy is a reasonable next step for further
      diagnostic examination of patients who display nodular high FDG uptake in the
      colon. Diffuse FDG uptake often is associated with normal findings at
      colonoscopy, while segmental high uptake may imply inflammation.

PMID- 12202715
TI  - The empty delta sign.

PMID- 12202716
TI  - Subcortical lacunar lesions: an MR imaging finding in patients with cerebral
      autosomal dominant arteriopathy with subcortical infarcts and
      leukoencephalopathy.
AB  - PURPOSE: To assess the prevalence and distribution of subcortical lacunar lesions
      (SLLs) in patients with cerebral autosomal dominant arteriopathy with subcortical
      infarcts and leukoencephalopathy (CADASIL), to determine whether SLLs are an
      abnormal finding by studying their prevalence in healthy subjects, and to assess
      whether SLLs occur in other conditions associated with small vessel disease and
      white matter areas of high signal intensity (WMH). MATERIALS AND METHODS: The
      presence of SLLs, their location, and their relation to other abnormalities were
      assessed on magnetic resonance (MR) images (T1-weighted, T2-weighted, and fluid
      attenuated inversion-recovery) obtained in 34 CADASIL patients and 20 healthy
      family members. Three additional control groups of healthy volunteers, elderly
      patients with vascular risk factors, and patients with another hereditary small
      vessel disease were also screened for the presence and location of SLLs.
      Sensitivity and specificity of the presence of SLLs for the diagnosis of CADASIL
      were assessed. RESULTS: SLLs were found in 20 (59%) of CADASIL patients.
      Incidence of SLLs increased with age (20%, <30 years; 50%, 30-50 years; 80%, >50
      years). SLLs invariably occurred in the anterior temporal lobes and in areas
      where diffuse WMH expanded into arcuate fibers. From the anterior temporal lobe,
      the lesions could extend dorsally into the temporal lobes and rostrally into the
      frontal lobes. Lesions were not found in the parietal and occipital lobes. None
      of the control subjects had SLLs. Specificity and sensitivity of SLLs for CADASIL
      were 100% and 59%, respectively. CONCLUSION: SLLs are an abnormal finding at MR
      imaging that frequently occur in CADASIL patients.

PMID- 12202717
TI  - Relative cerebral blood volume measurements in intracranial mass lesions:
      interobserver and intraobserver reproducibility study.
AB  - PURPOSE: To assess inter- and intraobserver reproducibility for different
      techniques of measuring relative cerebral blood volume (rCBV) in patients with
      intracranial mass lesions. MATERIALS AND METHODS: Three independent observers
      (neuroradiology fellows) who were blinded to the histopathologic diagnosis
      performed rCBV measurements in 50 patients with various intracranial mass
      lesions. Three different methods were compared. With method 1, placement of a
      single region of interest was guided by a color overlay map. With methods 2 and
      3, the highest rCBV value and the mean of repeated rCBV measurements,
      respectively, were recorded. Calculations of the intraclass correlation
      coefficient, coefficient of variation (CV), and descriptive statistics were used
      to determine the levels of reproducibility. A multiple linear regression model
      was used to evaluate for possible explanatory factors for interobserver variance.
      RESULTS: Method 2 had, overall, the best reproducibility of all techniques, with
      an intraclass interobserver correlation coefficient of 0.71 (indicating good
      agreement), interobserver CV of 30%, and intraobserver CV in the range of 32%
      41%. Measurement variations between observers correlated significantly (P <.001)
      with increasing rCBV values. CONCLUSION: In this study, interobserver and
      intraobserver reproducibility of rCBV measurements were clinically acceptable.

PMID- 12202718
TI  - More reliable noninvasive visualization of the cerebral veins and dural sinuses:
      comparison of three MR angiographic techniques.
AB  - PURPOSE: To compare the visualization of cerebral veins and dural sinuses at
      contrast material-enhanced three-dimensional (3D) fast low-angle shot (FLASH)
      magnetic resonance (MR) angiography, time-of-flight (TOF) MR angiography, and
      phase-contrast MR angiography. MATERIALS AND METHODS: The authors prospectively
      compared the two-dimensional source images, multiplanar reconstructed images, and
      maximum intensity projection angiograms obtained at contrast-enhanced 3D radio
      frequency-spoiled FLASH MR angiography in 20 patients with those obtained at TOF
      and phase-contrast MR angiographic examinations. Two neuroradiologists in
      consensus determined the number of visualized cortical veins and graded the
      quality of visualization of veins and sinuses as intense and continuous, faint
      and continuous, or noncontinuous. Statistical analysis was performed with the
      nonparametric sign test and the Wilcoxon matched pairs sign rank test. RESULTS:
      The cortical veins, inferior sagittal sinus, and cavernous sinuses were
      visualized best with FLASH MR angiography (P <.003). The Trolard and Labbe veins
      were visualized equally well with the FLASH and TOF sequences. For septal,
      internal cerebral, and Rosenthal left basal vein visualization, phase-contrast MR
      angiography was inferior to the FLASH and TOF MR angiographic examinations (P
      <.05). The quality of visualization of the thalamostriate and Galen veins and of
      the superior sagittal, rectal, and transverse sinuses was the same at all MR
      angiographic examinations. CONCLUSION: Three-dimensional FLASH MR angiography
      depicts some venous structures better than do TOF and phase-contrast MR
      angiographic examinations. The depiction of other veins is the same with 3D FLASH
      and TOF sequences.

PMID- 12202719
TI  - Adult cerebral malaria: prognostic importance of imaging findings and correlation
      with postmortem findings.
AB  - PURPOSE: To correlate imaging abnormalities, clinical features, and postmortem
      findings in patients with proved cerebral malaria. MATERIALS AND METHODS: Twenty
      one patients aged 17-50 years with cerebral malaria consented to undergo
      transverse nonenhanced (10-mm sections) and contrast material-enhanced (8-mm
      sections in posterior fossa and 10-mm sections in supratentorial region) CT on
      admission (n = 21) and on day 10 (n = 6), with thin sections (5 mm) obtained in
      the area of abnormality. All CT scans were evaluated for diffuse cerebral edema,
      focal parenchymal abnormalities, and hemorrhage. CT findings were categorized as
      normal, diffuse cerebral edema, and edema with thalamic hypoattenuation without
      or with cerebellar hypoattenuation. Spearman rank correlation test was performed.
      RESULTS: Initial scans were normal in seven patients with mild disease (median
      Acute Physiology and Chronic Health Evaluation [APACHE] II score of 7, median
      Glasgow Coma Scale [GCS] score of 10), and all survived. Of eight patients with
      diffuse cerebral edema (GCS > or = 8; median APACHE II, 21), six survived.
      Cerebral edema with thalamic and cerebellar white matter hypoattenuation was seen
      in five patients. All had GCS score of 6 or less, median APACHE II score of 26,
      and multiorgan failure; none survived. One patient (GCS = 6) had thalamic
      hypoattenuation without cerebellar lesions. He survived with mild residual
      hemiparesis. Diffuse petechial hemorrhages were seen in the cerebrum and
      cerebellum at autopsy in all seven patients who died. These petechial hemorrhages
      were not visualized on CT scans. CT findings did not correlate with degree of
      parasitemia. CONCLUSION: CT findings correlate well with level of consciousness
      and severity of disease but underestimate the extent of disease at pathologic
      examination. A normal CT scan indicates a favorable outcome, whereas cerebellar
      hypoattenuation portends a poor outcome.

PMID- 12202720
TI  - Effects of exposure of CHO-K1 cells to a 10-T static magnetic field.
AB  - PURPOSE: To evaluate whether exposure to strong static magnetic fields (SMFs), of
      up to 10 T, affects the growth and cycle distribution of and the micronucleus
      formation in monolayered Chinese hamster ovary CHO-K1 cells. MATERIALS AND
      METHODS: The authors developed a system to expose cultured cells to strong SMFs
      immediately after the cells are seeded. Cell growth rate was evaluated according
      to cell number count. Cell cycle distribution experiments were performed by using
      flow cytometric analysis. In these experiments, the cells were exposed to SMFs
      for up to 4 days. The frequency of micronucleus formation with only SMF exposure
      at x-ray irradiation was analyzed at microscopic observation. RESULTS: Long-term
      exposure to a 10-T SMF for up to 4 days did not affect cell growth rate or cell
      cycle distribution. Exposure to SMFs alone did not affect micronucleus frequency.
      In x-ray-irradiated cells, exposure to a 1-T SMF did not affect micronucleus
      frequency, but exposure to a 10-T SMF resulted in a significant (P <.05) increase
      in micronucleus frequency. CONCLUSION: Strong (10-T) SMFs have no effect on cell
      growth, cell cycle distribution, or micronucleus frequency, but they may cause an
      increase in the micronucleus formation induced by 4-Gy x rays.

PMID- 12202721
TI  - Radio-frequency ablation increases intratumoral liposomal doxorubicin
      accumulation in a rat breast tumor model.
AB  - PURPOSE: To determine whether intratumoral accumulation of liposomal doxorubicin
      or free unencapsulated doxorubicin is increased when combined with radio
      frequency (RF) ablation. MATERIALS AND METHODS: Two 1.2-1.5-cm R3230 mammary
      adenocarcinomas were grown within the mammary fat pads of 19 female Fischer rats.
      One tumor of each pair was treated with RF ablation (tip temperature, 70 degrees
      C +/- 2 [SD]; 120 mA +/- 75) for 5 minutes, whereas the other tumor was a
      control. Intravenous liposomal doxorubicin (1 mg in 500 micro L, n = 6) or
      intravenous free unencapsulated doxorubicin (n = 7) was administered immediately
      following RF ablation. Doxorubicin was extracted in acid alcohol from tumors 24
      hours following RF ablation, and fluorescent spectrophotometry was used to
      quantify extracted doxorubicin. Comparisons of intratumoral doxorubicin
      accumulation in tumors treated with RF ablation and in untreated tumors were
      analyzed with parametric (paired Student t test) and nonparametric (Wilcoxon rank
      sum test) statistics. Findings at autoradiography with densitometry (six
      additional tumors) demonstrated the spatial distribution of the intratumoral
      accumulation of liposomal doxorubicin. RESULTS: When RF ablation preceded
      administration of liposomal doxorubicin, mean intratumoral doxorubicin
      concentration was 5.6 micro g/g +/- 2.1 (range, 1.9-7.7 micro g/g), whereas 1.0
      micro g/g +/- 0.4 (range, 0.5-1.5 micro g/g) was present in control tumors not
      treated with RF ablation (P <.05). Thus, there was a mean 7.1-fold +/- 4.9
      increase in intratumoral doxorubicin accumulation following RF ablation (range,
      2.1-14.5-fold) compared with the amount without RF pretreatment (P <.05).
      Increased intratumoral accumulation was not seen in animals receiving free
      doxorubicin with (mean, 0.4 micro g/g +/- 0.1) or without (mean, 0.8 micro g/g +/
      0.4) RF pretreatment (P =.07). Autoradiographic findings demonstrated
      accumulation of liposomal doxorubicin in a peripheral rim of tumor adjacent to
      the zone of coagulation. CONCLUSION: RF ablation augments the delivery of
      systemic antineoplastic agents such as liposomal doxorubicin.

PMID- 12202722
TI  - Left ventricular remodeling after infarction: sequential MR imaging with oral
      nicorandil therapy in rat model.
AB  - PURPOSE: To use magnetic resonance (MR) imaging in quantification of the short-
      and long-term effects of therapy with orally administered nicorandil on left
      ventricular (LV) geometry and function independent of infarction size. MATERIALS
      AND METHODS: Forty-six rats were subjected to reperfused infarction and randomly
      divided into two groups. Group 1 rats (n = 21) were treated with nicorandil (3
      mg/kg/day in drinking water) for 4 days before infarction and 8 weeks after
      infarction (hereafter, the nicorandil group). Group 2 rats (n = 25) received tap
      water for the same period and served as the control group. Mesoporphyrin- (as a
      necrosis-specific agent) enhanced MR imaging was used to define necrotic
      myocardium on day 2 after infarction in all 46 animals. Contrast material
      enhanced MR images showed large but identical infarction size in 11 control and
      11 nicorandil rats. Only these 22 rats underwent repeat MR imaging at 8 weeks
      after infarction. The following variables were measured: LV volumes, ejection
      fraction, mass, wall thickness, and infarction size. Student t test and analysis
      of variance for repeated measurements were used for statistical analysis.
      RESULTS: The size of the necrotic region on mesoporphyrin-enhanced MR images was
      39% +/- 3 of the size of the left ventricle in the control group and 41% +/- 2 in
      the nicorandil group (difference not significant, unpaired Student t test).
      Pretreatment with nicorandil for 6 days before imaging did not reduce LV dilation
      or improve function compared with those in control animals with identical
      infarction size. Eight weeks after infarction, control animals showed
      deterioration in LV function, wall thinning, and gradient in regional dysfunction
      (analysis of variance test). Nicorandil produced significant salutary effects on
      LV ejection fraction (37% +/- 3 in the nicorandil group vs 24% +/- 3 in the
      control group), end-diastolic volume (0.53 mL +/- 0.03 vs 0.65 mL +/- 0.04), end
      systolic volume (0.36 mL +/- 0.03 vs 0.49 mL +/- 0.05), LV wall thickening in
      remote noninfarcted myocardium (28% +/- 2 vs 19% +/- 1), and a rim of infarction
      (16% +/- 2 vs 8% +/- 1) (P <.05 for all parameters). The increase in LV mass was
      reduced in the nicorandil group (0.73 g +/- 0.03) compared with that in the
      control group (0.89 g +/- 0.04) (P <.05). CONCLUSION: In animals studied
      longitudinally, MR imaging demonstrated the deleterious changes in LV geometry
      and function in the period after infarction and the salutary effects of medical
      therapy.

PMID- 12202723
TI  - EKG-triggered CT data acquisition to reduce variability in coronary arterial
      calcium score.
AB  - PURPOSE: To test the hypothesis that computed tomographic (CT) scanning during
      optimal electrocardiographic (EKG) triggering can minimize image motion artifact
      and reduce interexamination variation of coronary arterial calcification (CAC)
      score at electron-beam CT. MATERIALS AND METHODS: Two hundred patients underwent
      electron-beam CT once and again 5 minutes later to evaluate interexamination
      variability of CAC score. Group 1 (104 patients) underwent scanning with use of
      an optimal EKG-triggering protocol (EKG triggering performed individually at the
      time of least coronary arterial motion during the cardiac cycle); group 2 (96
      patients) underwent scanning with use of conventional 80% R-R interval triggering
      (the most common protocol with the electron-beam CT scanner). Interexamination,
      intraobserver, and interobserver variations of CAC measurements were compared
      between groups by using unpaired t tests for both Agatston and volumetric scores
      (in square millimeters). RESULTS: Coronary arterial motion artifacts were found
      in 26% (27 of 104) versus 80% (77 of 96) of patients in groups 1 and 2,
      respectively (P <.0001). Intraobserver, interobserver, and interexamination
      variabilities in volumetric score were derived, with values of 1.2%, 9.2%, and
      15.9% in group 1 and 2.1%, 11.3%, and 25.9% in group 2, respectively.
      Interexamination variabilities in both Agatston and volumetric score were
      significantly reduced with individualized EKG triggering, as compared with
      conventional triggering (P <.05), but intra- and interobserver variabilities were
      not (P >.05). CONCLUSION: Optimal EKG triggering improves the reproducibility of
      CAC measurement by reducing coronary arterial motion artifacts.

PMID- 12202724
TI  - Real-time MR image acquisition during high-dose dobutamine hydrochloride stress
      for detecting left ventricular wall-motion abnormalities in patients with
      coronary arterial disease.
AB  - PURPOSE: To compare the accuracy of real-time magnetic resonance (MR) imaging
      with that of standard echo-planar MR imaging for detecting myocardial wall-motion
      abnormalities at rest and during dobutamine hydrochloride-induced stress in
      patients with coronary arterial disease. MATERIALS AND METHODS: In 22 patients
      with coronary arterial disease, left ventricular wall motion was examined at rest
      and during dobutamine hydrochloride stress, by using echo-planar MR imaging and a
      new technique with real-time segmented k-space turbo gradient-echo echo-planar MR
      imaging (repetition time, 16.5 msec; echo time, 6.8 msec). Wall-motion
      abnormalities were determined visually for each perfusion territory, and Cohen
      kappa coefficients were calculated for real-time imaging in comparison with echo
      planar imaging. Coronary angiography was performed in all patients. Sensitivity
      and specificity for real-time and echo-planar imaging were calculated for
      detecting significant coronary arterial stenosis. RESULTS: kappa values for
      detecting wall-motion abnormalities at real-time imaging, in comparison with echo
      planar MR imaging, were 0.97 at rest and 0.94 at maximum dobutamine hydrochloride
      stress. At comparison with those of angiography, the sensitivity and specificity
      for detecting significant coronary arterial stenosis were 88% (14 of 16 patients)
      and 83% (five of six patients), respectively, for echo-planar imaging and 81% (13
      of 16 patients) and 83% (five of six patients), respectively, for real-time
      imaging. CONCLUSION: Real-time MR imaging is possible under stress conditions and
      allows accurate detection of wall-motion abnormalities.

PMID- 12202725
TI  - Drug-induced pneumonitis: thin-section CT findings in 60 patients.
AB  - PURPOSE: To describe thin-section computed tomographic (CT) findings in patients
      with drug-induced pneumonitis, to compare these CT findings, and to correlate
      them with arterial oxygen tension level. MATERIALS AND METHODS: Thin-section CT
      scans obtained in 60 patients with drug-induced pneumonitis were evaluated
      retrospectively. The patients had 31 cases of antineoplastic agent-induced
      pneumonitis and 29 cases of nonneoplastic agent-induced pneumonitis (antibiotic
      agent, 20 cases; herbal medicine [sho-saiko-to], four cases; antirheumatic agent,
      three cases; phenytoin, one case; disodium cromoglycate, one case). CT scans were
      reviewed by two chest radiologists in consensus. Correlation between arterial
      oxygen tension level and the extent of disease at CT was available in 21
      patients. These two factors were compared by using the Spearman rank correlation
      coefficient. RESULTS: The predominant findings in antineoplastic agent-induced
      pneumonitis were diffuse or multifocal ground-glass opacities with intralobular
      interstitial thickening. The predominant CT findings in antibiotic agent-induced
      pneumonitis were patchy ground-glass opacities with centrilobular opacities and
      interlobular septal lines. The predominant CT findings in herbal medicine-induced
      pneumonitis were diffuse ground-glass opacities with patchy consolidation.
      Interlobular septal lines and centrilobular opacities were observed more
      frequently in antibiotic agent-induced pneumonitis, and intralobular interstitial
      thickening was observed more frequently in antineoplastic agent-induced
      pneumonitis. A significant correlation was established between arterial oxygen
      tension level and extent of disease at CT (r = -0.84, P <.05). CONCLUSION: In
      addition to ground-glass opacities and interlobular septal lines, the most common
      thin-section CT findings were intralobular interstitial thickening, observed in
      antineoplastic agent-induced pneumonitis, and centrilobular opacities, observed
      in antibiotic-induced pneumonitis.

PMID- 12202726
TI  - Performance parameters for screening and diagnostic mammography: specialist and
      general radiologists.
AB  - PURPOSE: To evaluate performance parameters for radiologists in a practice of
      breast imaging specialists and general diagnostic radiologists who interpret a
      large series of consecutive screening and diagnostic mammographic studies.
      MATERIALS AND METHODS: Data (ie, patient age; family history of breast cancer;
      availability of previous mammograms for comparison; and abnormal interpretation,
      cancer detection, and stage 0-I cancer detection rates) were derived from review
      of mammographic studies obtained from January 1997 through August 2001. The
      breast imaging specialists have substantially more initial training in
      mammography and at least six times more continuing education in mammography, and
      they interpret 10 times more mammographic studies per year than the general
      radiologists. Differences between specialist and general radiologist performances
      at both screening and diagnostic examinations were assessed for significance by
      using Student t and chi(2) tests. RESULTS: The study involved 47,798 screening
      and 13,286 diagnostic mammographic examinations. Abnormal interpretation rates
      for screening mammography (ie, recall rate) were 4.9% for specialists and 7.1%
      for generalists (P <.001); and for diagnostic mammography (ie, recommended biopsy
      rate), 15.8% and 9.9%, respectively (P <.001). Cancer detection rates at
      screening mammography were 6.0 cancer cases per 1,000 examinations for
      specialists and 3.4 per 1,000 for generalists (P =.007); and at diagnostic
      mammography, 59.0 per 1,000 and 36.6 per 1,000, respectively (P <.001). Stage 0-I
      cancer detection rates at screening mammography were 5.3 cancer cases per 1,000
      examinations for specialists and 3.0 per 1,000 for generalists (P =.012); and at
      diagnostic mammography, 43.9 per 1,000 and 27.0 per 1,000, respectively (P
      <.001). CONCLUSION: Specialist radiologists detect more cancers and more early
      stage cancers, recommend more biopsies, and have lower recall rates than general
      radiologists.

PMID- 12202728
TI  - Undetected malignancies of the breast: dynamic contrast-enhanced MR imaging at
      1.0 T.
AB  - PURPOSE: To assess the prevalence and characteristics of malignant breast lesions
      not identified with magnetic resonance (MR) imaging. MATERIALS AND METHODS:
      Breast tissue specimens were obtained in 464 of 967 patients who had undergone
      dynamic gadolinium-enhanced T1-weighted fast low-angle shot three-dimensional MR
      imaging of both breasts. A comparison of sensitivity, specificity, and predictive
      values of the prospectively recorded findings of mammography, ultrasonography
      (US), and MR imaging with the histopathologic results was performed with receiver
      operating characteristic (ROC) curve analysis. MR imaging examination findings
      that caused a false-negative diagnosis were reviewed to identify possible sources
      of error. RESULTS: Histopathologic analysis revealed 244 benign and 354 malignant
      lesions. The sensitivity values for mammography, mammography combined with US, MR
      imaging alone, and the combination of all three modalities were 73.7%, 88.1%,
      88.4%, and 95.5%, and the areas under the ROC curves were 0.744, 0.829, 0.850,
      and 0.876, respectively. Twenty-eight (8.4%) of 334 invasive and 13 (65%) of 20
      intraductal carcinomas were missed with MR imaging. In eight cases, motion
      artifacts (n = 1), tumor location near or beyond the outer boundary of the field
      of view (n = 3), inadequate infusion of the contrast material (n = 1), and
      masking of the tumors by intensively enhanced surrounding glandular tissue (n =
      3) were identified as adequate explanations for the false-negative results. The
      remaining missed breast cancers (n = 33) exhibited very diffuse growth patterns
      or were 5 mm or smaller. CONCLUSION: MR imaging did not depict 41 of 354
      malignant tumors for several reasons.

PMID- 12202727
TI  - Does training in the Breast Imaging Reporting and Data System (BI-RADS) improve
      biopsy recommendations or feature analysis agreement with experienced breast
      imagers at mammography?
AB  - PURPOSE: To determine whether training in the Breast Imaging Reporting and Data
      System (BI-RADS) improves observer performance and agreement with the consensus
      of experienced breast imagers with regard to mammographic feature analysis and
      final assessment. MATERIALS AND METHODS: A test set of mammograms was developed,
      with 54 proven lesions consisting of 28 masses (nine [32%] malignancies) and 26
      microcalcifications (10 [38%] malignancies). Three experienced breast imagers
      reviewed cases independently and by means of consensus. Twenty-three practicing
      mammogram-interpreting physicians reviewed mammograms before and after a day's
      lectures on BI-RADS. Observer performance before and after training was measured
      by means of agreement (kappa) with consensus description and assessments, rate of
      biopsy of malignant and benign lesions, and areas under receiver operating
      characteristic (ROC) curves. Performance was also measured for 11 participants 2
      3 months after training. RESULTS: Improved agreement with consensus feature
      analysis was found for mass margins and/or asymmetries, with a pretraining
      generalized kappa value of 0.36 and a posttraining generalized kappa value of
      0.41. Similar improvement was seen for description of calcification morphology
      (pretraining kappa value of 0.36 improving to 0.44 after training). No
      improvement was seen in describing calcification distribution. Final assessments
      were more consistent after training, with a pretraining kappa value of 0.31, as
      compared with 0.45 after training. The mean biopsy rate for malignant lesions
      improved from 73% (range, 53%-89%) before training to 88% (range, 74%-100%) after
      training, with minimal increase in mean biopsy rate of benign lesions (43%
      [range, 26%-60%] before to 51% [range, 31%-63%] after training), and no net
      change in area under the ROC curve, as compared with histopathologic findings.
      For the subset of participants with delayed follow-up, no significant decline in
      posttraining results was seen. CONCLUSION: BI-RADS training resulted in improved
      agreement with the consensus of experienced breast imagers for feature analysis
      and final assessment. It is important that trainees showed improved rates of
      recommending biopsy for malignant lesions. This effect was maintained over 2-3
      months.

PMID- 12202729
TI  - Interventional MR imaging at 1.5 T: quantification of sound exposure.
AB  - Sound pressure levels (SPLs) during interventional magnetic resonance (MR)
      imaging may create an occupational hazard for the interventional radiologist (ie,
      the potential risk of hearing impairment). Therefore, A-weighted and linear
      continuous-equivalent SPLs were measured at the entrance of a 1.5-T MR imager
      during cardiovascular and real-time pulse sequences. The SPLs ranged from 81.5 to
      99.3 dB (A-weighted scale), and frequencies were from 1 to 3 kHz. SPLs for the
      interventional radiologist exceeded a safe SPL of 80 dB (A-weighted scale) for
      all sequences; therefore, hearing protection is recommended.

PMID- 12202730
TI  - Thorax: low-dose contrast-enhanced three-dimensional MR angiography with
      subsecond temporal resolution--initial results.
AB  - The purpose of the study was to implement a three-dimensional (3D) magnetic
      resonance (MR) angiographic technique with acquisition times on the order of 800
      msec with use of a spoiled gradient-echo pulse sequence (repetition time, 1.60
      msec; echo time, 0.65 msec) and bolus intravenous injection of contrast material
      doses as small as 6 mL. High-spatial-resolution conventional MR angiography
      performed with 30 mL of gadopentetate dimeglumine was the reference standard. As
      implemented, subsecond 3D MR angiography allowed temporal sampling that was rapid
      enough to depict short-lived processes, as illustrated in patients with shunts
      and dissections. With small contrast material doses and subsecond frame rates, it
      is also possible to measure pulmonary arteriovenous circulation times with this
      3D MR angiographic technique.

PMID- 12202731
TI  - Lung: feasibility of a method for changing tube current during low-dose helical
      CT.
AB  - A method for changing the tube current during helical scanning was applied to low
      dose computed tomography (CT) in the lung. The changing method resulted in
      significant equalization of image noise in various lung sections compared with
      that at scanning with constant tube current. Detectability of nodules was
      equivalent between 60 mA and the changing method, whereas degradation occurred at
      20 mA. This method seems feasible for the low-dose CT of lung cancer screening.

PMID- 12202732
TI  - Coronary artery bypass graft flow: qualitative evaluation with cine single
      detector row CT and comparison with findings at angiography.
AB  - A four-point ordinal-scale qualitative flow index was used for assessment of
      patency of 75 coronary artery bypass grafts in 26 patients examined with spiral
      computed tomography (CT). CT findings were compared with selective graft
      angiographic findings. Of 54 open grafts, 52 were patent at initial selective
      graft angiography and 50 were patent at spiral CT; accuracy rates were 97% (73 of
      75) and 95% (71 of 75), respectively. Spiral CT flow index agreed with
      angiographically determined flow in 85% (95% CI: 0.77, 0.93) of grafts. The kappa
      statistic demonstrated very good to excellent intermodality (0.75) and
      interobserver (0.89) agreement. Spiral CT may be a feasible means of assessing
      quality of flow in bypass grafts.

PMID- 12202733
TI  - Spatial normalization of spine MR images for statistical correlation of lesions
      with clinical symptoms.
AB  - An image analysis method was developed for spatial normalization of spine
      magnetic resonance images. A deformable shape model of the spine is first
      constructed, and it is subsequently used by an automated algorithm to find a
      shape transformation that places patient data into a stereotactic space. Very
      good agreement with manual segmentations was observed. The main application of
      this method is in lesion-deficit analysis for determining associations between
      structural damage and clinical symptoms.

PMID- 12202734
TI  - A patient's viewpoint on a current controversy.

PMID- 12202735
TI  - Screening for lung cancer: been there and done that.

PMID- 12202736
TI  - Mortality rate and screening.

PMID- 12202737
TI  - Screening breast US.

PMID- 12202738
TI  - Emphasis on CIs when P values are not appropriate.

PMID- 12202739
TI  - Apophyseal joint and intervertebral disk injuries caused by hyperflexion and
      hyperextension.

PMID- 12202740
TI  - Diagnosis of Snapping Triceps with US.

PMID- 12202744
TI  - Rapid atmospheric CO2 changes associated with the 8,200-years-B.P. cooling event.
AB  - By applying the inverse relation between numbers of leaf stomata and atmospheric
      CO2 concentration, stomatal frequency analysis of fossil birch leaves from lake
      deposits in Denmark reveals a century-scale CO2 change during the prominent
      Holocene cooling event that occurred in the North Atlantic region between 8,400
      and 8,100 years B.P. In contrast to conventional CO2 reconstructions based on ice
      cores from Antarctica, quantification of the stomatal frequency signal
      corroborates a distinctive temperature-CO2 correlation. Results indicate a global
      CO2 decline of approximately 25 ppm by volume over approximately 300 years. This
      reduction is in harmony with observed and modeled lowering of North Atlantic sea
      surface temperatures associated with a short-term weakening of thermohaline
      circulation.

PMID- 12202745
TI  - Self-perpetuating epigenetic pili switches in bacteria.
AB  - Bacteria have developed an epigenetic phase variation mechanism to control cell
      surface pili-adhesin complexes between heritable expression (phase ON) and
      nonexpression (phase OFF) states. In the pyelonephritis-associated pili (pap)
      system, global regulators [catabolite gene activator protein (CAP), leucine
      responsive regulatory protein (Lrp), DNA adenine methylase (Dam)] and local
      regulators (PapI and PapB) control phase switching. Lrp binds cooperatively to
      three pap DNA binding sites, sites 1-3, proximal to the papBA pilin promoter in
      phase OFF cells, whereas Lrp is bound to sites 4-6 distal to papBA in phase ON
      cells. Two Dam methylation targets, GATC(prox) and GATC(dist), are located in Lrp
      binding sites 2 and 5, respectively. In phase OFF cells, binding of Lrp at sites
      1-3 inhibits methylation of GATC(prox), forming the phase OFF DNA methylation
      pattern (GATC(dist) methylated, GATC(prox) nonmethylated). Binding of Lrp at
      sites 1-3 blocks pap pili transcription and reduces the affinity of Lrp for sites
      4-6. Together with methylation of GATC(dist), which inhibits Lrp binding at sites
      4-6, the phase OFF state is maintained. We hypothesize that transition to the
      phase ON state requires DNA replication to dissociate Lrp and generate a
      hemimethyated GATC(dist) site. PapI and methylation of GATC(prox) act together to
      increase the affinity of Lrp for sites 4-6. Binding of Lrp at the distal sites
      protects GATC(dist) from methylation, forming the phase ON methylation pattern
      (GATC(dist) nonmethyated, GATC(prox) methylated). Lrp binding at sites 4-6
      together with cAMP-CAP binding 215.5 bp upstream of the papBA transcription
      start, is required for activation of pilin transcription. The first gene product
      of the papBA transcript, PapB, helps maintain the switch in the ON state by
      activating papI transcription, which in turn maintains Lrp binding at sites 4-6.

PMID- 12202746
TI  - Serotonin mediates food-odor associative learning in the nematode
      Caenorhabditiselegans.
AB  - We demonstrate that Caenorhabditis elegans is able to form an association between
      the presence of the odorant benzaldehyde and the food content of its environment.
      When exposed to 100% benzaldehyde for 1 h in the absence of food the naive
      attractive response is reduced, and we have found that this olfactory adaptation
      is attenuated by the presence of food. Contrary to nonassociative (single
      stimulus) learning theory, this response is not a function of the total time of
      exposure to benzaldehyde but rather an associative function of the ability of
      benzaldehyde to predict a nutrient-deficient environment. Genetic and
      pharmacological evidence revealed that the effects of food in this learning
      paradigm are mediated by serotonergic signaling.

PMID- 12202747
TI  - Somatic hypermutation of the AID transgene in B and non-B cells.
AB  - Somatic hypermutation (SHM) of the Ig genes is required for affinity maturation
      of the humoral response to foreign antigens. Activation-induced cytidine
      deaminase (AID), which is specifically expressed in germinal center centroblasts,
      is indispensable for this process. Expression of AID is sufficient to activate
      SHM in hybridomas, non-B cells, and Escherichia coli, suggesting that it
      initiates the mutational process by deaminating DNA. However, the cis-acting
      sequences that are responsible for targeting AID activity to the variable (V)
      region of Ig genes are unknown. Here we show that expression of AID in B cell
      lines (i.e., Burkitt's lymphoma Ramos and hybridoma P1-5) not only causes
      hypermutation of Ig sequences, but also of the AID transgene itself. Because it
      is possible that B cell-specific transacting factors bind to and recruit the
      "mutator" to the AID transgene, we tested whether the AID transgene can mutate in
      non-B cells. Indeed, we show that expression of AID in Chinese hamster ovary
      cells causes SHM of both the Ig and AID transgenes. These data suggest that high
      transcription rates alone may predispose any gene to mutation by AID but do not
      preclude that there are specific B cell factors that account for the extremely
      high rate of V mutation in vivo and its targeting to the V region.

PMID- 12202748
TI  - Novel domains and orthologues of eukaryotic transcription elongation factors.
AB  - The passage of RNA polymerase II across eukaryotic genes is impeded by the
      nucleosome, an octamer of histones H2A, H2B, H3 and H4 dimers. More than a dozen
      factors in the yeast Saccharomyces cerevisiae are known to facilitate
      transcription elongation through chromatin. In order to better understand the
      evolution and function of these factors, their sequences have been compared with
      known protein, EST and DNA sequences. Elongator subcomplex components Elp4p and
      Elp6p are shown to be homologues of ATPases, yet with substitutions of amino
      acids critical for ATP hydrolysis, and novel orthologues of Elp5p are detectable
      in human, and other animal, sequences. The yeast CP complex is shown to contain a
      likely inactive homologue of M24 family metalloproteases in Spt16p/Cdc68p and a 2
      fold repeat in Pob3p, the orthologue of mammalian SSRP1. Archaeal DNA-directed
      RNA polymerase subunit E" is shown to be the orthologue of eukaryotic Spt4p, and
      Spt5p and prokaryotic NusG are shown to contain a novel 'NGN' domain. Spt6p is
      found to contain a domain homologous to the YqgF family of RNases, although this
      domain may also lack catalytic activity. These findings imply that much of the
      transcription elongation machinery of eukaryotes has been acquired subsequent to
      their divergence from prokaryotes.

PMID- 12202749
TI  - Displacement of DNA-PKcs from DNA ends by the Werner syndrome protein.
AB  - The DNA-dependent protein kinase (DNA-PK) complex, which is composed of a DNA
      dependent kinase subunit (DNA-PKcs) and the Ku70/80 heterodimer, is involved in
      DNA double-strand break repair by non-homologous end joining (NHEJ). Ku70/80
      interacts with the Werner syndrome protein (WRN) and stimulates WRN exonuclease
      activity. To investigate a possible function of WRN in NHEJ, we have examined the
      relationship between DNA-PKcs, Ku and WRN. First, we showed that WRN forms a
      complex with DNA-PKcs and Ku in solution. Next, we determined whether this
      complex assembles on DNA ends. Interestingly, the addition of WRN to a Ku:DNA
      PKcs:DNA complex results in the displacement of DNA-PKcs from the DNA, indicating
      that the triple complex WRN:Ku:DNA-PKcs cannot form on DNA ends. The displacement
      of DNA-PKcs from DNA requires the N- and C-terminal regions of WRN, both of which
      make direct contact with the Ku70/80 heterodimer. Moreover, exonuclease assays
      indicate that DNA-PKcs does not protect DNA from the nucleolytic action of WRN.
      These results suggest that WRN may influence the mechanism by which DNA ends are
      processed.

PMID- 12202750
TI  - Predicted structure and phyletic distribution of the RNA-binding protein Hfq.
AB  - Hfq, a bacterial RNA-binding protein, was recently shown to contain the Sm1
      motif, a characteristic of Sm and LSm proteins that function in RNA processing
      events in archaea and eukaryotes. In this report, comparative structural modeling
      was used to predict a three-dimensional structure of the Hfq core sequence. The
      predicted structure aligns with most major features of the Methanobacterium
      thermoautotrophicum LSm protein structure. Conserved residues in Hfq are
      positioned at the same structural locations responsible for subunit assembly and
      RNA interaction in Sm proteins. A highly conserved portion of Hfq assumes a
      structural fold similar to the Sm2 motif of Sm proteins. The evolution of the Hfq
      protein was explored by conducting a BLAST search of microbial genomes followed
      by phylogenetic analysis. Approximately half of the 140 complete or nearly
      complete genomes examined contain at least one gene coding for Hfq. The presence
      or absence of Hfq closely followed major bacterial clades. It is absent from high
      level clades and present in the ancient Thermotogales-Aquificales clade and all
      proteobacteria except for those that have undergone major reduction in genome
      size. Residues at three positions in Hfq form signatures for the beta/gamma
      proteobacteria, alpha proteobacteria and low GC Gram-positive bacteria groups.

PMID- 12202751
TI  - Distinct domains in the CArG-box binding factor A destabilize tetraplex forms of
      the fragile X expanded sequence d(CGG)n.
AB  - Formation of hairpin or tetraplex structures of the FMR1 gene d(CGG)n sequence
      triggers its expansion, setting off fragile X syndrome. In searching for proteins
      that destabilize d(CGG)n secondary structures we purified from rat liver
      quadruplex telomeric DNA binding protein 42 (qTBP42) that disrupts G'2
      bimolecular tetraplex d(CGG)n while paradoxically stabilizing the G'2 structure
      of the telomeric sequence d(TTAGGG)n. Based on peptide sequence homology of
      qTBP42 and mouse CArG-box binding factor A (CBF-A), we provide direct evidence
      that recombinant CBF-A protein is physically and immunochemically
      indistinguishable from qTBP42 and that it too destabilizes G'2 d(CGG)n while
      stabilizing G'2 d(TTAGGG)n. We inquired whether CBF-A employs the same or
      different domains to differentially interact with G'2 d(CGG)n and G'2 d(TTAGGG)n.
      Mutant CBF-A proteins that lack each or combinations of its five conserved
      motifs: RNP1(1), RNP1(2), RNP2(1), RNP2(2) and ATP/GTP-binding box were tested
      for their G'2 d(CGG)n destabilization and G'2 d(TTAGGG)n stabilization
      activities. We find that either RNP1(1) or the ATP/GTP motifs are necessary and
      sufficient for G'2 d(CGG)n destabilization whereas RNP2(1) suppresses
      destabilization by either one of these two motifs. Neither RNP1(1) nor the
      ATP/GTP motif are required for G'2 d(TTAGGG)n stabilization. Hence, CBF-A employs
      different domains to destabilize G'2 d(CGG)n or stabilize G'2 d(TTAGGG)n.

PMID- 12202752
TI  - Drosophila melanogaster RECQ5/QE DNA helicase: stimulation by GTP binding.
AB  - The Drosophila melanogaster RECQ5/QE gene encodes a member of the DNA helicase
      family comprising the Escherichia coli RecQ protein and products of the human
      Bloom's, Werner's, and Rothmund-Thomson syndrome genes. The full-length product
      of RECQ5/QE was expressed in the baculovirus system and was purified. Gel
      filtration experiments indicated that RECQ5/QE was present in an oligomeric
      state. The RECQ5/QE protein hydrolyzed ATP and even more actively GTP in the
      presence of single-stranded DNA. ATP drove the DNA helicase activity of RECQ5/QE,
      whereas GTP had little effect. GTP exhibited a stimulatory effect on DNA
      unwinding when it was used together with ATP. This effect was more apparent with
      non-hydrolyzable GTP analogs, such as GTPgammaS and GMPPNP. These results
      indicate that GTP binding to RECQ5/QE triggers its DNA helicase activity. GTP
      binding increased the rate of strand separation without affecting the S(0.5)
      (K(m)) values for the substrates during the DNA helicase reaction. The data
      collectively suggest that the RECQ5/QE protein is activated upon GTP binding
      through the ATP-binding site.

PMID- 12202753
TI  - The switch region on Leishmania major chromosome 1 is not required for mitotic
      stability or gene expression, but appears to be essential.
AB  - The Leishmania genome project reference strain, Leishmania major Friedlin, is
      trisomic for chromosome 1. The complete sequence of this chromosome has revealed
      that the genes are grouped into two large clusters of the polycistronic type,
      each borne by one DNA strand and located on each side of a 1.6-kb sequence often
      termed the switch region. Several hypotheses concerning the role of this switch
      region have been put forward (region of initiation of transcription for both gene
      clusters, origin of replication or centromeric sequence). In the present study,
      we have deleted this region on the three copies of chromosome 1 by sequential
      targeted replacements. The absence of the switch region did not alter the mitotic
      stability of the three deleted chromosomes. This region therefore does not appear
      necessary for chromosomal replication or segregation. However, during the third
      targeting round, which aimed at knocking out the last switch region, a fourth
      copy of chromosome 1 that retained this region appeared in all clones analysed.
      This suggests that the persistence of this switch region is necessary for
      parasite survival. We then showed that the presence/absence of the switch region
      did not act upon the expression of a resistance marker gene inserted beforehand
      into the left gene cluster of the same chromosomal molecule. This result suggests
      that the presence of this 1.6-kb sequence is not necessary for the expression of
      all genes on chromosome 1.

PMID- 12202754
TI  - DNA double-strand break-induced phosphorylation of Drosophila histone variant
      H2Av helps prevent radiation-induced apoptosis.
AB  - The response of eukaryotic cells to the formation of a double-strand break (DSB)
      in chromosomal DNA is highly conserved. One of the earliest responses to DSB
      formation is phosphorylation of the C-terminal tail of H2A histones located in
      nucleosomes near the break. Histone variant H2AX and core histone H2A are
      phosphorylated in mammals and budding yeast, respectively. We demonstrate the DSB
      induced phosphorylation of histone variant H2Av in Drosophila melanogaster. H2Av
      is a member of the H2AZ family of histone variants. Ser137 within an SQ motif
      located near the C- terminus of H2Av was phosphorylated in response to gamma
      irradiation in both tissue culture cells and larvae. Phosphorylation was detected
      within 1 min of irradiation and detectable after only 0.3 Gy of radiation
      exposure. Photochemically induced DSBs, but not general oxidative damage or UV
      induced nicking of DNA, caused H2Av phosphorylation, suggesting that
      phosphorylation is DSB specific. Imaginal disc cells from Drosophila expressing a
      mutant allele of H2Av with its C-terminal tail deleted, and therefore unable to
      be phosphorylated, were more sensitive to radiation-induced apoptosis than were
      wildtype controls, suggesting that phosphorylation of H2Av is important for
      repair of radiation-induced DSBs. These observations suggest that in addition to
      providing the function of an H2AZ histone, H2Av is also the functional homolog in
      Drosophila of H2AX.

PMID- 12202755
TI  - Partial reconstitution of human RNase P in HeLa cells between its RNA subunit
      with an affinity tag and the intact protein components.
AB  - An RNA affinity tag was incorporated into the RNA subunit of human nuclear RNase
      P. The tagged RNA assembled with the protein components of RNase P inside HeLa
      cells to generate an active enzyme. Because of the specificity of the RNA tag to
      streptavidin, the reconstituted complex could be separated from the native enzyme
      and other ribonucleoproteins (particularly RNase MRP) by streptavidin agarose
      chromatography and could be recovered by the eluting agent, biotin. A mutant,
      tagged RNase P RNA, whose P3 domain was partially replaced, could not
      reconstitute with the proteins to yield an active enzyme. The P3 domain,
      therefore, is critical for the structure and function of RNase P.

PMID- 12202756
TI  - Antiproliferative effect in chronic myeloid leukaemia cells by antisense peptide
      nucleic acids.
AB  - Peptide nucleic acid (PNA) is a synthetic DNA analogue that is resistant to
      nucleases and proteases and binds with exceptional affinity to RNA. Because of
      these properties PNA has the potential to become a powerful therapeutic agent to
      be used in vivo. Until now, however, the use of PNA in vivo has not been much
      investigated. Here, we have attempted to reduce the expression of the bcr/abl
      oncogene in chronic myeloid leukaemia KYO-1 cells using a 13mer PNA sequence
      (asPNA) designed to hybridise to the b2a2 junction of bcr/abl mRNA. To enhance
      cellular uptake asPNA was covalently linked to the basic peptide VKRKKKP (NLS
      asPNA). Moreover, to investigate the cellular uptake by confocal microscopy, both
      PNAs were linked by their N-terminus to fluorescein (FL). Studies of uptake,
      carried out at 4 and 37 degrees C on living KYO-1 cells stained with hexidium
      iodide, showed that both NLS-asPNA-FL and asPNA-FL were taken up by the cells,
      through a receptor-independent mechanism. The intracellular amount of NLS-asPNA
      FL was about two to three times higher than that of asPNA-FL. Using a semi
      quantitative RT- PCR technique we found that 10 micro M asPNA and NLS-asPNA
      reduced the level of b2a2 mRNA in KYO-1 cells to 20 +/- 5% and 60 +/- 10% of the
      control, respectively. Western blot analysis showed that asPNA promoted a
      significant inhibition of p210(BCR/ABL) protein: residual protein measured in
      cells exposed for 48 h to asPNA was approximately 35% of the control.
      Additionally, asPNA impaired cell growth to 50 +/- 5% of the control and
      inhibited completion of the cell cycle. In summary, these results demonstrate
      that a PNA 13mer is taken up by KYO-1 cells and is capable of producing a
      significant and specific down-regulation of the bcr/abl oncogene involved in
      leukaemogenesis.

PMID- 12202757
TI  - Polyamine structural effects on the induction and stabilization of liquid
      crystalline DNA: potential applications to DNA packaging, gene therapy and
      polyamine therapeutics.
AB  - DNA undergoes condensation, conformational transitions, aggregation and
      resolubilization in the presence of polyamines, positively charged organic
      molecules present in all cells. Under carefully controlled environmental
      conditions, DNA can also transform to a liquid crystalline state in vitro. We
      undertook the present work to examine the ability of spermidine, N4
      methylspermidine, spermine, N1-acetylspermine and a group of tetramine, pentamine
      and hexamine analogs of spermine to induce and stabilize liquid crystalline DNA.
      Liquid crystalline textures were identified under a polarizing microscope. In the
      absence of polyamines, calf thymus DNA assumed a diffused, planar cholesteric
      phase with entrapped bubbles when incubated on a glass slide at 37 degrees C. In
      the presence of spermidine and spermine, the characteristic fingerprint textures
      of the cholesteric phase, adopting a hexagonal order, were obtained. The helical
      pitch was 2.5 micro m. The final structures were dendrimeric and crystalline when
      DNA was treated with spermine homologs and bis(ethyl) derivatives. A cholesteric
      structure was observed when DNA was treated with a hexamine at 37 degrees C. This
      structure changed to a hexagonal dendrimer with fluidity on prolonged incubation.
      These data show a structural specificity effect of polyamines on liquid
      crystalline phase transitions of DNA and suggest a possible physiological
      function of natural polyamines.

PMID- 12202758
TI  - Transcriptome analysis of Escherichia coli using high-density oligonucleotide
      probe arrays.
AB  - Microarrays traditionally have been used to analyze the expression behavior of
      large numbers of coding transcripts. Here we present a comprehensive approach for
      high-throughput transcript discovery in Escherichia coli focused mainly on
      intergenic regions which, together with analysis of coding transcripts, provides
      us with a more complete insight into the organism's transcriptome. Using a whole
      genome array, we detected expression for 4052 coding transcripts and identified
      1102 additional transcripts in the intergenic regions of the E.coli genome.
      Further classification reveals 317 novel transcripts with unknown function. Our
      results show that, despite sophisticated approaches to genome annotation, many
      cellular transcripts remain unidentified. Through the experimental identification
      of all RNAs expressed under a specific condition, we gain a more thorough
      understanding of all cellular processes.

PMID- 12202759
TI  - Synthesis and polymerase incorporation of 5'-amino-2',5'-dideoxy-5'-N
      triphosphate nucleotides.
AB  - Owing to the markedly increased reactivity of amino functional groups versus
      hydroxyls, the 5'-amino-5'-deoxy nucleoside and nucleotide analogs have proven
      widely useful in biological, pharmaceutical and genomic applications. However,
      synthetic procedures leading to these analogs have not been fully explored, which
      may possibly have limited the scope of their utility. Here we describe the
      synthesis of the 5'-amino-2',5'-dideoxy analogs of adenosine, cytidine,
      guanosine, inosine and uridine from their respective naturally occurring
      nucleosides via the reduction of 5'-azido-2',5'-dideoxy intermediates using the
      Staudinger reaction, and the high yield conversion of these modified nucleosides
      and 5'-amino-5'-deoxythymidine to the corresponding 5'-N-triphosphates through
      reaction with trisodium trimetaphosphate in the presence of
      tris(hydroxymethyl)aminomethane (Tris). We also show that each of these
      nucleotide analogs can be efficiently incorporated into DNA by the Klenow
      fragment of Escherichia coli DNA polymerase I when individually substituted for
      its naturally occurring counterpart. Mild acid treatment of the resulting DNA
      generates polynucleotide fragments that arise from specific cleavage at each
      modified nucleotide, providing a sequence ladder for each base. Because the
      ladders are generated after the extension, the corresponding products may be
      manipulated by enzymatic and/or purification processes. The potential utility of
      this extension-cleavage procedure in genomic sequence analysis is discussed.

PMID- 12202760
TI  - Sequence-specific protection of plasmid DNA from restriction endonuclease
      hydrolysis by pyrrole-imidazole-cyclopropapyrroloindole conjugates.
AB  - The pyrrole-imidazole (Py-Im) triamide-cyclopropa pyrroloindole (CPI) conjugates
      ImPyImLDu86 (7) and ImImPyLDu86 (14) were synthesized and their alkylating
      activities and inhibitory effects on DNA hydrolysis by restriction endonucleases
      were examined. Sequencing gel analysis demonstrated that conjugates 7 and 14
      specifically alkylated DNA at 5'-CGCGCG-3' and 5'-PyGGCCPu-3', respectively.
      Agarose gel electrophoresis indicated that incubation of a supercoiled plasmid,
      pSPORT I (4109 bp), with conjugate 7 effectively inhibited its hydrolysis by
      BssHII (5'-G_CGCGC-3'), whereas conjugate 14 had no effect on this hydrolysis.
      These results suggest that conjugate 7 sequence-specifically inhibits the
      hydrolysis of DNA by BssHII. Sequence-specific alkylation by the Py-Im triamide
      CPI conjugates was further confirmed by inhibition of the Eco52I (5'-C_GGCCG-3')
      hydrolysis of conjugate 14-treated pQBI PGK (5387 bp). In clear contrast,
      hydrolysis of pQB1 PGK by DraI (3'-TTT_AAA-3') was not inhibited by 5 micro M
      conjugate 14. That ImImPy did not inhibit the hydrolysis of pQB1 PGK indicates
      that covalent bond formation is necessary for inhibition. A similar experiment,
      using linear pQBI PGK, achieved the same extent of protection of the DNA with
      approximately half the concentration of conjugate 14 as was required to protect
      supercoiled DNA from hydrolysis.

PMID- 12202762
TI  - Determination of base and backbone contributions to the thermodynamics of
      premelting and melting transitions in B DNA.
AB  - In previous papers of this series the temperature-dependent Raman spectra of
      poly(dA).poly(dT) and poly(dA-dT).poly(dA-dT) were used to characterize
      structurally the melting and premelting transitions in DNAs containing
      consecutive A.T and alternating A.T/T.A base pairs. Here, we describe procedures
      for obtaining thermodynamic parameters from the Raman data. The method exploits
      base-specific and backbone-specific Raman markers to determine separate
      thermodynamic contributions of A, T and deoxyribosyl-phosphate moieties to
      premelting and melting transitions. Key findings include the following: (i) Both
      poly(dA).poly(dT) and poly(dA-dT). poly(dA-dT) exhibit robust premelting
      transitions, due predominantly to backbone conformational changes. (ii) The
      significant van't Hoff premelting enthalpies of poly(dA).poly(dT) [DeltaH(vH)(pm)
      = 18.0 +/- 1.6 kcal x mol(-1) (kilocalories per mole cooperative unit)] and
      poly(dA-dT).poly(dA-dT) (DeltaH(vH)(pm) = 13.4 +/- 2.5 kcal x mol(-1)) differ by
      an amount (approximately 4.6 kcal x mol(-1)) estimated as the contribution from
      three-centered inter-base hydrogen bonding in (dA)(n).(dT)(n) tracts. (iii) The
      overall stacking free energy of poly(dA). poly(dT) [-6.88 kcal x mol(bp)(-1)
      (kilocalories per mole base pair)] is greater than that of poly(dA-dT). poly(dA
      dT) (-6.31 kcal x mol(bp)(-1)). (iv) The difference between stacking free
      energies of A and T is significant in poly(dA).poly(dT) (DeltaDeltaG(st) = 0.8 +/
      0.3 kcal. mol(bp)(-1)), but marginal in poly(dA-dT).poly(dA-dT) (DeltaDeltaG(st)
      = 0.3 +/- 0.3 kcal x mol(bp)(-1)). (v) In poly(dA). poly(dT), the van't Hoff
      parameters for melting of A (DeltaH(vH)(A) = 407 +/- 23 kcal.mol(-1),
      DeltaS(vH)(A) = 1166 +/- 67 cal. degrees K(-1) x mol(-1), DeltaG(vH(25 degrees
      C))(A) = 60.0 +/- 3.2 kcal x mol(-1)) are clearly distinguished from those of T
      (DeltaH(vH)(T) = 185 +/- 38 kcal x mol(-1), DeltaS(vH)(T) = 516 +/- 109 cal.
      degrees K(-1) x mol(-1), DeltaG(vH(25 degrees C))(T) = 27.1 +/- 5.5 kcal x mol(
      1)). (vi) Similar relative differences are observed in poly(dA-dT). poly(dA-dT)
      (DeltaH(vH)(A) = 333 +/- 54 kcal x mol(-1), DeltaS(vH)(A) = 961 +/- 157 cal.
      degrees K(-1) x mol(-1), DeltaG(vH(25 degrees C))(A) = 45.0 +/- 7.6 kcal x mol(
      1); DeltaH(vH)(T) = 213 +/- 30 kcal x mol(-1), DeltaS(vH)(T) = 617 +/- 86 cal.
      degrees K(-1) x mol(-1), DeltaG(vH(25 degrees C))(T) = 29.3 +/- 4.9 kcal x mol(
      1)). The methodology employed here distinguishes thermodynamic contributions of
      base stacking, base pairing and backbone conformational ordering in the molecular
      mechanism of double-helical B DNA formation.

PMID- 12202761
TI  - Genome-wide detection of tissue-specific alternative splicing in the human
      transcriptome.
AB  - We have developed an automated method for discovering tissue-specific regulation
      of alternative splicing through a genome-wide analysis of expressed sequence tags
      (ESTs). Using this approach, we have identified 667 tissue-specific alternative
      splice forms of human genes. We validated our muscle-specific and brain-specific
      splice forms for known genes. A high fraction (8/10) were reported to have a
      matching tissue specificity by independent studies in the published literature.
      The number of tissue-specific alternative splice forms is highest in brain, while
      eye-retina, muscle, skin, testis and lymph have the greatest enrichment of tissue
      specific splicing. Overall, 10-30% of human alternatively spliced genes in our
      data show evidence of tissue-specific splice forms. Seventy-eight percent of our
      tissue-specific alternative splices appear to be novel discoveries. We present
      bioinformatics analysis of several tissue-specific splice forms, including
      automated protein isoform sequence and domain prediction, showing how our data
      can provide valuable insights into gene function in different tissues. For
      example, we have discovered a novel kidney-specific alternative splice form of
      the WNK1 gene, which appears to specifically disrupt its N-terminal kinase domain
      and may play a role in PHAII hypertension. Our database greatly expands knowledge
      of tissue-specific alternative splicing and provides a comprehensive dataset for
      investigating its functional roles and regulation in different human tissues.

PMID- 12202763
TI  - Structural insights by molecular dynamics simulations into differential repair
      efficiency for ethano-A versus etheno-A adducts by the human alkylpurine-DNA N
      glycosylase.
AB  - 1,N6-ethenoadenine adducts (epsilonA) are formed by known environmental
      carcinogens and found to be removed by human alkylpurine-DNA N-glycosylase
      (APNG). 1,N6-ethanoadenine (EA) adducts differ from epsilonA by change of a
      double bond to a single bond in the 5-member exocyclic ring and are formed by
      chloroethyl nitrosoureas, which are used in cancer therapy. In this work, using
      purified recombinant human APNG, we show that EA is a substrate for the enzyme.
      However, the excision efficiency of EA was 65-fold lower than that of epsilonA.
      Molecular dynamics simulation produced similar structural motifs for epsilonA and
      EA when incorporated into a DNA duplex, suggesting that there are no specific
      conformational features in the DNA duplex which can account for the differences
      in repair efficiency. However, when EA was modeled into the APNG active site,
      based on the APNG/epsilonA-DNA crystallographic coordinates, in structures
      produced by 2 ns molecular dynamics simulation, we observed weakening in the
      stacking interaction between EA and aromatic side chains of the key amino acids
      in the active site. In contrast, the planar epsilonA is better stacked at the
      enzyme active site. We propose that the observed destabilization of the EA adduct
      at the active site, such as reduced stacking interactions, could account for the
      biochemically observed weaker recognition of EA by APNG as compared to epsilonA.

PMID- 12202764
TI  - Gene expression profiling of the aging mouse cardiac myocytes.
AB  - Heart disease remains the most frequent cause of death in the general population
      with increasing incidence in the elderly population. The pathologic failure of
      the aging heart may be related to structural and functional alterations in
      cardiac muscle cells. However, the molecular mechanisms underlying the aging
      related decline in cardiac muscle function are largely unknown. To provide the
      first analysis of cardiac aging at the level of gene expression, we established
      and compared cDNA libraries from apparently healthy young and aged mouse
      ventricular cardiac muscle cells. We report the identification of genes that
      exhibit aging-related changes of mRNA levels. Aging expression profiles in aged
      hearts indicate decreased cellular adaptation and protection against stress
      induced injury together with the development of contractile dysfunction. The data
      suggest reduced activity of the mitochondrial electron transport system and
      reduced levels of cardiac-specific transcription regulators. The cardiomyocyte
      aging profile of gene expression displays similarities with known heart
      disorders. Genes whose mRNA levels change with aging in cardiomyocytes might
      profoundly affect pathological changes in the heart.

PMID- 12202766
TI  - Definition and prediction of the full range of transcription factor binding sites
      -the hepatocyte nuclear factor 1 dimeric site.
AB  - In animals, transcription factor binding sites are hard to recognize because of
      their extensive variation. We therefore characterized the general relationship
      between a specific protein-binding site and its DNA sequence and used this
      relationship to generate a predictive algorithm for searching other DNA
      sequences. The experimental process was defined by studying hepatocyte nuclear
      factor 1 (HNF1), which binds DNA as a dimer on two inverted-repeat 7-bp half
      sites separated by one base. The binding model was based on the equivalence of
      the two half sites, which was confirmed in examples where specific modified sites
      were compared. Binding competition analysis was used to determine the effects of
      substitution of all four bases at each position in the half site. From these
      data, a weighted half-site matrix was generated and the full site was evaluated
      as the sum of two half-site scores. This process accurately predicted even weak
      binding sites that were significantly different from the consensus sequence. The
      predictions also showed a direct correlation with measured protein binding.

PMID- 12202765
TI  - Drosophila damage-specific DNA-binding protein 1 (D-DDB1) is controlled by the
      DRE/DREF system.
AB  - We succeeded in cloning the gene, termed d-ddb1, for a Drosophila homolog of the
      p127 subunit of the human damage-specific DNA-binding protein, thought to
      recognize (6-4) photoproducts and related structures. In Drosophila, the gene
      product (D-DDB1) also appeared to play a role as a repair factor, d-ddb1 knockout
      Kc cells generated with a RNAi method being sensitive to UV. In addition, UV or
      methyl methanesulfonate treatment increased d-ddb1 transcripts. However, we found
      that the gene is controlled by the DRE/DREF system, which is generally
      responsible for activating the promoters of proliferation-related genes.
      Moreover, during Drosophila development, the transcription of d-ddb1 changed
      greatly, with the highest levels in unfertilized eggs, indicating that external
      injury to DNA is not essential to D-DDB1 function. Interestingly, as with UV
      irradiation-induced transfer of D-DDB1 to the nucleus from the cytoplasm, during
      spermatogenesis the protein transiently shifted from one cell compartment to the
      other. The results indicate that D-DDB1 not only contributes to the DNA repair
      system, but also has a role in cell proliferation and development.

PMID- 12202767
TI  - Characterisation of site-biased DNA methyltransferases: specificity, affinity and
      subsite relationships.
AB  - DNA methylation is now seen as a primary signal in the cell for mediating
      transcriptional repression through chromatin formation. The construction and
      evaluation of enzymes capable of influencing this process in vivo is therefore of
      significant interest. We have fused the C5-cytosine DNA methyltransferases,
      M.HhaI and M.HpaII, which both methylate 4 bp sequences containing a CpG
      dinucleotide, to a three zinc finger protein recognising a 9 bp DNA sequence. DNA
      methylation analyses demonstrate specific DNA methylation by both enzymes at
      target sites comprising adjacent methyltransferase and zinc finger subsites,
      targeted M.HpaII being the most specific. Binding analysis of the targeted
      M.HpaII enzyme reveals an 8-fold preference for binding to its target site,
      compared to binding to a zinc finger site alone, and an 18-fold preference over
      binding to a methyltransferase site alone, thereby demonstrating enhanced binding
      by the fusion protein, compared to its component proteins. Both DNA binding and
      methylation are specific for the target site up to separations of approximately
      40 bp between the zinc finger and methyltransferase subsites. Ex vivo plasmid
      methylation experiments are also described that demonstrate targeted methylation.
      These targeted enzymes, however, are shown to be not fully mono-functional,
      retaining a significant non-targeted activity most evident at elevated protein
      concentrations.

PMID- 12202768
TI  - Dnmt3L is a transcriptional repressor that recruits histone deacetylase.
AB  - The Dnmt3L protein belongs to the Dnmt3 family of DNA methyltransferases by
      virtue of its sequence homology in the plant homeodomain (PHD)-like motif. Dnmt3L
      is essential for the establishment of maternal genomic imprints and, given its
      lack of key methyltransferase motifs, is more likely to act as a regulator of
      methylation rather than as an enzyme that methylates DNA. Here, we show that
      Dnmt3L, like Dnmt3a and Dnmt3b, interacts both in vitro and in vivo with the
      histone deacetylase HDAC1. Consistent with the binding to a deacetylase, Dnmt3L
      purifies histone deacetylase activity from nuclear extracts. We find that Dnmt3L
      can repress transcription and that this repression is dependent on HDAC1 and is
      relieved by treatment with the HDAC inhibitor trichostatin A. Binding of Dnmt3L
      to HDAC1 as well as its repressive function require the PHD-like motif. Our
      results indicate that Dnmt3L plays a role in transcriptional regulation and that
      recruitment of the HDAC repressive machinery is a shared and conserved feature of
      the Dnmt3 family. The fact that, despite the absence of a methyltransferase
      domain, Dnmt3L retains the capacity to contact deacetylase further substantiates
      the notion that the Dnmts can repress transcription independently of their
      methylating activities.

PMID- 12202769
TI  - Functional analysis of iceA1, a CATG-recognizing restriction endonuclease gene in
      Helicobacter pylori.
AB  - iceA1 in Helicobacter pylori is a homolog of nlaIIIR, which encodes the CATG
      specific restriction endonuclease NlaIII in Neisseria lactamica. Analysis of
      iceA1 sequences from 49 H.pylori strains shows that a full-length NlaIII-like ORF
      is present in 10 strains, including CH4, but in other strains, including strain
      60190, the ORFs are truncated due to a variety of mutations. Our goal was to
      determine whether iceA1 can encode a NlaIII-like endonuclease. Overexpression in
      Escherichia coli of iceA1 from CH4, but not from 60190, yielded NlaIII-like
      activity, indicating that the full-length iceA1 is a functional endonuclease
      gene. Repair of the iceA1 frameshift mutation in strain 60190 and its expression
      in E.coli yielded functional NlaIII-like activity. We conclude that iceA1 in CH4
      is a functional restriction endonuclease gene, while iceA1 in 60190 is not, due
      to a frameshift mutation, but that its repair restores its restriction
      endonuclease activity.

PMID- 12202770
TI  - Defects in interstrand cross-link uncoupling do not account for the extreme
      sensitivity of ERCC1 and XPF cells to cisplatin.
AB  - The anticancer drug cisplatin reacts with DNA leading to the formation of
      interstrand and intrastrand cross-links that are the critical cytotoxic lesions.
      In contrast to cells bearing mutations in other components of the nucleotide
      excision repair apparatus (XPB, XPD, XPG and CSB), cells defective for the ERCC1
      XPF structure-specific nuclease are highly sensitive to cisplatin. To determine
      if the extreme sensitivity of XPF and ERCC1 cells to cisplatin results from
      specific defects in the repair of either intrastrand or interstrand cross-links
      we measured the elimination of both lesions in a range of nucleotide excision
      repair Chinese hamster mutant cell lines, including XPF- and ERCC1-defective
      cells. Compared to the parental, repair-proficient cell line all the mutants
      tested were defective in the elimination of both classes of adduct despite their
      very different levels of increased sensitivity. Consequently, there is no clear
      relationship between initial incisions at interstrand cross-links or removal of
      intrastrand adducts and cellular sensitivity. These results demonstrate that the
      high cisplatin sensitivity of ERCC1 and XPF cells likely results from a defect
      other than in excision repair. In contrast to other conventional DNA cross
      linking agents, we found that the repair of cisplatin adducts does not involve
      the formation of DNA double-strand breaks. Surprisingly, XRCC2 and XRCC3 cells
      are defective in the uncoupling step of cisplatin interstrand cross-link repair,
      suggesting that homologous recombination might be initiated prior to excision of
      this type of cross-link.

PMID- 12202771
TI  - Challenging artificial genetic systems: thymidine analogs with 5-position sulfur
      functionality.
AB  - Eight different polymerases, chosen from evolutionary families A (Taq, Tfl,
      HotTub and Tth) and B (Pfu, Pwo, Vent and Deep Vent), were examined for their
      ability to incorporate 5-position modified 2'-deoxyuridine derivatives that carry
      a protected thiol group appended via different linkers containing either three or
      four carbon atoms. This represents the first attempt to incorporate the thiol
      functionality into DNA via enzymatic synthesis. Each polymerase-substrate
      combination was evaluated using a hierarchy of increasingly more difficult
      challenges, starting with incorporation of a single derivative, proceeding to
      incorporation of two derivatives at adjacent sites and non-adjacent sites, then
      examining the ability of the polymerase to accept the derivative within the
      template, and concluding with a challenge involving PCR. The evaluation of thiol
      bearing 2'-deoxyuridine derivatives was then extended to consider their chemical
      stabilities. Stability was found to be less than satisfactory when the thiol
      functionality has a 'propargylic' relationship to the unsaturation in the linker.
      The best polymerase-appendage combination used the polymerase from Pyrococcus
      woesei (Pwo) and the 5'-tBu-SS-CH2-CH2-C [triple bond] C-linker. This pair
      supported PCR amplification and therefore should have value in artificial in
      vitro selection experiments. Indeed, we discovered that Pwo and Pfu preferred the
      derivative triphosphate over TTP, the natural substrate, in competition studies.
      These studies confirm an earlier suggestion that membership of an evolutionary
      family of polymerases is a partial predictor of the ability of the polymerase to
      accept 5-modified 2'-deoxyuridines. Considerable differences are displayed by
      different members within a polymerase family, however. This remains curious, as
      the ability of the polymerase to replicate natural DNA with high fidelity and its
      propensity to exclude unnatural analogs are presumed to be correlated.

PMID- 12202773
TI  - Promiscuous methylation of non-canonical DNA sites by HaeIII methyltransferase.
AB  - The cytosine C5 methyltransferase M.HaeIII recognises and methylates the central
      cytosine of its canonical site GGCC. Here we report that M.HaeIII can also, with
      lower efficiency, methylate cytosines located in a wide range of non-canonical
      sequences. Using bisulphite sequencing we mapped the methyl- cytosine residues in
      DNA methylated in vitro and in vivo by M.HaeIII. Methyl-cytosine residues were
      observed in multiple sequence contexts, most commonly, but not exclusively, at
      star sites (sites differing by a single base from the canonical sequence). The
      most frequently used star sites had changes at positions 1 and 4, but there is
      little or no methylation at star sites changed at position 2. The rate of
      methylation of non-canonical sites can be quite significant: a DNA substrate
      lacking a canonical site was methylated by M.HaeIII in vitro at a rate only an
      order of magnitude slower than an otherwise identical substrate containing the
      canonical site. In vivo methylation of non-canonical sites may therefore be
      significant and may have provided the starting point for the evolution of
      restriction-modification systems with novel sequence specificities.

PMID- 12202772
TI  - Mutations altering the cleavage specificity of a homing endonuclease.
AB  - The homing endonuclease I-CreI recognizes and cleaves a particular 22 bp DNA
      sequence. The crystal structure of I-CreI bound to homing site DNA has previously
      been determined, leading to a number of predictions about specific protein-DNA
      contacts. We test these predictions by analyzing a set of endonuclease mutants
      and a complementary set of homing site mutants. We find evidence that all
      structurally predicted I-CreI/DNA contacts contribute to DNA recognition and show
      that these contacts differ greatly in terms of their relative importance. We also
      describe the isolation of a collection of altered specificity I-CreI derivatives.
      The in vitro DNA-binding and cleavage properties of two such endonucleases
      demonstrate that our genetic approach is effective in identifying homing
      endonucleases that recognize and cleave novel target sequences.

PMID- 12202774
TI  - Prediction of consensus structural motifs in a family of coregulated RNA
      sequences.
AB  - Given a set of homologous or functionally related RNA sequences, the consensus
      motifs may represent the binding sites of RNA regulatory proteins. Unlike DNA
      motifs, RNA motifs are more conserved in structures than in sequences. Knowing
      the structural motifs can help us gain a deeper insight of the regulation
      activities. There have been various studies of RNA secondary structure
      prediction, but most of them are not focused on finding motifs from sets of
      functionally related sequences. Although recent research shows some new
      approaches to RNA motif finding, they are limited to finding relatively simple
      structures, e.g. stem-loops. In this paper, we propose a novel genetic
      programming approach to RNA secondary structure prediction. It is capable of
      finding more complex structures than stem-loops. To demonstrate the performance
      of our new approach as well as to keep the consistency of our comparative study,
      we first tested it on the same data sets previously used to verify the current
      prediction systems. To show the flexibility of our new approach, we also tested
      it on a data set that contains pseudoknot motifs which most current systems
      cannot identify. A web-based user interface of the prediction system is set up at
      http://bioinfo. cis.nctu.edu.tw/service/gprm/.

PMID- 12202775
TI  - Human non-synonymous SNPs: server and survey.
AB  - Human single nucleotide polymorphisms (SNPs) represent the most frequent type of
      human population DNA variation. One of the main goals of SNP research is to
      understand the genetics of the human phenotype variation and especially the
      genetic basis of human complex diseases. Non-synonymous coding SNPs (nsSNPs)
      comprise a group of SNPs that, together with SNPs in regulatory regions, are
      believed to have the highest impact on phenotype. Here we present a World Wide
      Web server to predict the effect of an nsSNP on protein structure and function.
      The prediction method enabled analysis of the publicly available SNP database
      HGVbase, which gave rise to a dataset of nsSNPs with predicted functionality. The
      dataset was further used to compare the effect of various structural and
      functional characteristics of amino acid substitutions responsible for phenotypic
      display of nsSNPs. We also studied the dependence of selective pressure on the
      structural and functional properties of proteins. We found that in our dataset
      the selection pressure against deleterious SNPs depends on the molecular function
      of the protein, although it is insensitive to several other protein features
      considered. The strongest selective pressure was detected for proteins involved
      in transcription regulation.

PMID- 12202777
TI  - Improved quantitative real-time RT-PCR for expression profiling of individual
      cells.
AB  - The real-time quantitative polymerase chain reaction (rtqPCR) has overcome the
      limitations of conventional, time-consuming quantitative PCR strategies and is
      maturing into a routine tool to quantify gene expression levels, following
      reverse transcription (RT) of mRNA into complementary DNA (cDNA). Expression
      profiling with single-cell resolution is highly desirable, in particular for
      complex tissues like the brain that contain a large variety of different cell
      types in close proximity. The patch-clamp technique allows selective harvesting
      of single-cell cytoplasm after recording of cellular activity. However,
      components of the cDNA reaction, in particular the reverse transcriptase itself,
      significantly inhibit subsequent rtqPCR amplification. Using undiluted single
      cell cDNA reaction mix directly as template for rtqPCR, I observed that the
      amplification kinetics of rtqPCRs were dramatically altered in a non-systematic
      fashion. Here, I describe a simple and robust precipitation protocol suitable for
      purification of single-cell cDNA that completely removes inhibitory RT components
      without detectable loss of cDNA. This improved single-cell real-time RT-PCR
      protocol provides a powerful tool to quantify differential gene expression of
      individual cells and thus could complement global microarray-based expression
      profiling strategies.

PMID- 12202776
TI  - Dictionary-driven protein annotation.
AB  - Computational methods seeking to automatically determine the properties
      (functional, structural, physicochemical, etc.) of a protein directly from the
      sequence have long been the focus of numerous research groups. With the advent of
      advanced sequencing methods and systems, the number of amino acid sequences that
      are being deposited in the public databases has been increasing steadily. This
      has in turn generated a renewed demand for automated approaches that can annotate
      individual sequences and complete genomes quickly, exhaustively and objectively.
      In this paper, we present one such approach that is centered around and exploits
      the Bio-Dictionary, a collection of amino acid patterns that completely covers
      the natural sequence space and can capture functional and structural signals that
      have been reused during evolution, within and across protein families. Our
      annotation approach also makes use of a weighted, position-specific scoring
      scheme that is unaffected by the over-representation of well-conserved proteins
      and protein fragments in the databases used. For a given query sequence, the
      method permits one to determine, in a single pass, the following: local and
      global similarities between the query and any protein already present in a public
      database; the likeness of the query to all available archaeal/
      bacterial/eukaryotic/viral sequences in the database as a function of amino acid
      position within the query; the character of secondary structure of the query as a
      function of amino acid position within the query; the cytoplasmic, transmembrane
      or extracellular behavior of the query; the nature and position of binding
      domains, active sites, post-translationally modified sites, signal peptides, etc.
      In terms of performance, the proposed method is exhaustive, objective and allows
      for the rapid annotation of individual sequences and full genomes. Annotation
      examples are presented and discussed in Results, including individual queries and
      complete genomes that were released publicly after we built the Bio-Dictionary
      that is used in our experiments. Finally, we have computed the annotations of
      more than 70 complete genomes and made them available on the World Wide Web at
      http://cbcsrv.watson.ibm.com/Annotations/.

PMID- 12202778
TI  - Cre recombinase-mediated inversion using lox66 and lox71: method to introduce
      conditional point mutations into the CREB-binding protein.
AB  - CREB-binding protein (CBP) is a multifunctional cofactor implicated in many
      intracellular signal transduction pathways. We aimed to investigate the
      involvement of CBP in the cAMP response element-binding protein (CREB)-mediated
      pathway. The point mutation Tyr658Ala in the CREB-binding domain (CBD) was shown
      to abolish the binding activity of CBP to phospho-CREB, the activated form of
      CREB. By using a mutant Cre/loxP recombination system, this point mutation was
      aimed to be generated in the mouse genome in a tissue- and time-specific manner.
      A targeting construct in which CBD exon 5 and inverted exon 5* containing the
      point mutation flanked by two mutant loxP sites (lox66 and lox71) oriented in a
      head-to-head position was generated. When Cre recombinase is present, the DNA
      flanked by the two mutant loxP sites is inverted, forming one loxP and one double
      mutated loxP site. As the double mutated loxP site shows low affinity for Cre
      recombinase, the favorable reaction leads to a product where the mutated exon 5*
      is placed into the position to be correctly transcribed and spliced. Inversion
      was observed to be complete in both bacteria and mouse embryonic stem cells. Our
      results indicate that this Cre- mediated inversion method is a valuable tool to
      introduce point mutations in the mouse genome in a regulatable manner.

PMID- 12202779
TI  - Single nucleotide polymorphism genotyping using short, fluorescently labeled
      locked nucleic acid (LNA) probes and fluorescence polarization detection.
AB  - Locked nucleic acids (LNAs) are synthetic nucleic acid analogs that bind to
      complementary target molecules (DNA, RNA or LNA) with very high affinity. At the
      same time, this binding affinity is decreased substantially when the hybrids thus
      formed contain even a single mismatched base pair. We have exploited these
      properties of LNA probes to develop a new method for single nucleotide
      polymorphism genotyping. In this method, very short (hexamer or heptamer) LNA
      probes are labeled with either rhodamine or hexachlorofluorescein (HEX), and
      their hybridization to target DNAs is followed by measuring the fluorescence
      polarization (FP) of the dyes. The formation of perfectly complementary double
      stranded hybrids gives rise to significant FP increases, whereas the presence of
      single mismatches results in very small or no changes of this parameter.
      Multiplexing of the assay can be achieved by using differentially labeled wild
      type and mutant specific probes in the same solution. The method is homogeneous,
      and because of the use of extremely short LNA probes, the generation of a
      universal set of genotyping reagents is possible.

PMID- 12202780
TI  - Multivariate curve resolution: a powerful tool for the analysis of conformational
      transitions in nucleic acids.
AB  - A successful application is reported of the multivariate curve resolution
      alternating least-squares method (MCR-ALS) for the analysis of nucleic acid
      melting and salt-induced transitions. Under conditions where several structures
      co-exist in a conformational equilibrium, MCR-ALS analysis of the UV and circular
      dichroism (CD) spectra at different temperatures, ionic strength and
      oligonucleotide concentration allows for the resolution of concentration profiles
      and pure spectra of the different species. The methodology is illustrated by the
      case of the cyclic oligonucleotide d<pTGCTCGCT>. The melting transition of this
      molecule at different oligonucleotide concentrations was studied at 0, 2 and 10
      mM MgCl2 by UV and CD spectroscopy. In addition, salt titration experiments were
      carried out at 21.0 and 54.0 degrees C. The MCR-ALS analysis indicates that three
      different conformations of this molecule co-exist in solution. In agreement with
      previous NMR studies, these conformations were assigned to a monomeric dumbbell
      like structure, a dimeric four-stranded conformation and a disordered (random
      coil) structure. The MCR-ALS methodology allows for a detailed analysis of how
      this equilibrium is affected by temperature, salt and oligonucleotide
      concentration.

PMID- 12202782
TI  - Why the epidermal growth factor receptor? The rationale for cancer therapy.
AB  - There is a need for new, selective anticancer agents that differentiate between
      malignant and nonmalignant cells. The benefits of such agents would include a
      higher therapeutic index and lower toxicity than conventional therapies. Although
      expressed in nonmalignant cells, the epidermal growth factor receptor (EGFR) is
      highly expressed in a variety of tumors, and its expression correlates with poor
      response to treatment, disease progression, and poor survival. Evidence for a
      role for the EGFR in the inhibition and pathogenesis of various cancers has led
      to the rational design and development of agents that selectively target this
      receptor. Activation of the EGFR signaling pathway in cancer cells has been
      linked with increased cell proliferation, angiogenesis, and metastasis, and
      decreased apoptosis. Preclinical data show that anti-EGFR therapies can inhibit
      these effects in vitro and in vivo. In addition, preclinical data confirm that
      many such agents have the potential to increase the effectiveness of current
      cytotoxic agents. Following accelerated drug development programs, phase III
      trials are now under way for a number of EGFR-targeted therapies, including the
      monoclonal antibody IMC-C225 and the EGFR-tyrosine kinase inhibitors ZD1839
      (Iressa) and OSI-774. Thus, the rationale for EGFR-targeted approaches to cancer
      treatment is apparent and now well established, and there is increasing evidence
      that they may represent a significant contribution to cancer therapy.

PMID- 12202783
TI  - ZD1839 (Iressa) in non-small cell lung cancer.
AB  - Despite the advent of cisplatin-based combination chemotherapy for advanced non
      small cell lung cancer (NSCLC), the prognosis for this patient population remains
      poor. Novel biologically targeted agents currently in development have the
      potential for greater efficacy against NSCLC, and possibly less toxicity than is
      associated with conventional cytotoxic chemotherapy. The epidermal growth factor
      receptor (EGFR) is recognized as a potentially useful target, and the small
      molecule, orally active EGFR-tyrosine kinase inhibitor ZD1839 (Iressa) is
      currently the furthest along in clinical development of the anti-EGFR agents.
      This review summarizes the currently available clinical data on the use of ZD1839
      in the treatment of NSCLC.

PMID- 12202784
TI  - ZD1839 (Iressa): for more than just non-small cell lung cancer.
AB  - ZD1839 (Iressa) is an orally active, selective epidermal growth factor receptor
      tyrosine kinase inhibitor that blocks signal transduction pathways involved in
      cell proliferation. Preclinical studies demonstrated that ZD1839 is a promising
      agent for the treatment of a wide range of tumors and has additive-to-synergistic
      effects when combined with radiation or chemotherapy in various cell lines and
      xenografts. Phase I clinical trials have reported that ZD1839 has acceptable
      tolerability and antitumor activity. In addition to non-small cell lung cancer,
      phase II/III studies are currently investigating ZD1839 as monotherapy or in
      combination therapy against prostate, breast, head and neck, gastric, and
      colorectal tumors.

PMID- 12202785
TI  - ZD1839 (Iressa): what's in it for the patient?
AB  - Although cytotoxic chemotherapy has had a significant impact on the treatment of
      some malignancies, its impact against most solid tumors is limited. This is
      especially true in the case of non-small cell lung cancer (NSCLC) in which about
      90% of patients ultimately die from metastatic disease. Although chemotherapy has
      produced modest improvements in response rates and survival in a subset of
      patients with advanced NSCLC, its primary objective remains to provide palliation
      of disabling disease-related symptoms. It is hoped that the introduction of new,
      rationally designed anticancer agents, with greater specificity and less
      toxicity, will improve the outcome for patients with a range of tumor types,
      including NSCLC. ZD1839 (Iressa) is the first of a new class of epidermal growth
      factor receptor tyrosine kinase inhibitors. The results of two large phase II
      trials have shown that ZD1839 provides clinically significant symptom relief for
      many patients with extensively pretreated advanced NSCLC. Moreover, this
      improvement in disease-related symptoms correlated with improved survival and
      tumor response. ZD1839 also had an acceptable tolerability profile: most drug
      related adverse events were mild and reversible and quite different from those
      typically associated with cytotoxic agents. Some patients also experienced
      improved quality of life, particularly those with a partial response or stable
      disease. Thus, ZD1839 offers a new treatment option providing meaningful symptom
      relief for many patients with advanced NSCLC.

PMID- 12202786
TI  - Epidermal growth factor receptor dependence in human tumors: more than just
      expression?
AB  - The epidermal growth factor receptor (EGFR) is a rational target for antitumor
      strategies. EGFR signaling causes increased proliferation, decreased apoptosis,
      and enhanced tumor cell motility and neo-angiogenesis. The EGFR is expressed or
      highly expressed in a variety of human tumors of epithelial origin. ZD1839
      (Iressa) is an orally active, selective EGFR tyrosine kinase inhibitor, which
      blocks signal transduction pathways implicated in proliferation and survival of
      cancer cells. The lack of a consistent method of evaluating levels of EGFR has
      caused a disparity in reports of the EGFR as a prognostic factor; however, for
      some tumors, EGFR is a strong prognostic indicator associated with more
      aggressive disease and reduced survival. So far, no clear association between
      EGFR levels and response to EGFR-targeted agents has been found. Preclinical
      studies with ZD1839 have noted a relationship between the two in some cases, but
      not others. EGFR signaling may be increased by a number of mechanisms in addition
      to high expression levels of EGFR, including receptor mutations,
      heterodimerization with other members of this receptor family such as HER2
      (erbB2), increased expression of (autocrine/ paracrine) ligands, and alterations
      in molecules that control receptor signaling output. Each of these components
      could be assessed to give an indication of the magnitude of EGFR signal
      amplification. Evaluation of signaling components downstream from EGFR should
      provide information on the activation of the EGFR pathway. Until EGFR-based
      assays predictive of a response to receptor-targeted therapies are available,
      there is no clear justification for stratifying patients by EGFR status or
      excluding patients with low EGFR levels from trials with ZD1839 or other EGFR
      inhibitors.

PMID- 12202787
TI  - Beta-diversity in tropical forests.

PMID- 12202788
TI  - A tiger tale.

PMID- 12202789
TI  - Nuclear physics. Belgrade lab sets new course after top-secret uranium grab.

PMID- 12202790
TI  - Environmental health. Critics see a tilt in a CDC science panel.

PMID- 12202791
TI  - Cosmology. NSF funds South Pole microwave telescope.

PMID- 12202792
TI  - Cell biology. Alliance launched to model E. coli.

PMID- 12202793
TI  - Neuroscience. Researchers thrilled with seminal discovery.

PMID- 12202794
TI  - Human subjects. Ethicists fault review of children's study.

PMID- 12202795
TI  - Analytical chemistry. Light touch identifies wisps of rogue DNA.

PMID- 12202796
TI  - Neuroscience. Sight, sound converge in owl's mental map.

PMID- 12202797
TI  - Economic espionage. Researcher acquitted of lab theft charge.

PMID- 12202798
TI  - Paleoanthropology. Glasnost for hominids: seeking access to fossils.

PMID- 12202799
TI  - Paleoanthropology. Can a fossil be too accessible?

PMID- 12202800
TI  - Electronic publishing. Online pioneer winds up lost in cyberspace.

PMID- 12202801
TI  - Biomedical science. Can money turn Singapore into a biotech juggernaut?

PMID- 12202802
TI  - Biomedical science. The lure of first-class science.

PMID- 12202803
TI  - Biomedical science. Many Asian nations grab for biomedical brass ring.

PMID- 12202805
TI  - Climate reconstruction. The value of multiple proxies.

PMID- 12202804
TI  - Ecology. National forests in the Amazon.

PMID- 12202806
TI  - Ecology. Fall and rise of the Black Sea ecosystem.

PMID- 12202807
TI  - Genetics and development. Zebrafish in the spotlight.

PMID- 12202808
TI  - X-ray astronomy-40 years on.

PMID- 12202809
TI  - Space science. How to cope with space weather.

PMID- 12202811
TI  - A warmer Arctic means change for all.

PMID- 12202812
TI  - Whither Arctic ice? Less of it, for sure.

PMID- 12202813
TI  - Even in the high Arctic, nothing is permanent.

PMID- 12202814
TI  - Feeling the pulse of modern Arctic life.

PMID- 12202815
TI  - Breaking up is far too easy.

PMID- 12202816
TI  - Dynamics of recent climate change in the Arctic.
AB  - The pattern of recent surface warming observed in the Arctic exhibits both polar
      amplification and a strong relation with trends in the Arctic Oscillation mode of
      atmospheric circulation. Paleoclimate analyses indicate that Arctic surface
      temperatures were higher during the 20th century than during the preceding few
      centuries and that polar amplification is a common feature of the past.
      Paleoclimate evidence for Holocene variations in the Arctic Oscillation is mixed.
      Current understanding of physical mechanisms controlling atmospheric dynamics
      suggests that anthropogenic influences could have forced the recent trend in the
      Arctic Oscillation, but simulations with global climate models do not agree. In
      most simulations, the trend in the Arctic Oscillation is much weaker than
      observed. In addition, the simulated warming tends to be largest in autumn over
      the Arctic Ocean, whereas observed warming appears to be largest in winter and
      spring over the continents.

PMID- 12202817
TI  - Mass balance of polar ice sheets.
AB  - Recent advances in the determination of the mass balance of polar ice sheets show
      that the Greenland Ice Sheet is losing mass by near-coastal thinning, and that
      the West Antarctic Ice Sheet, with thickening in the west and thinning in the
      north, is probably thinning overall. The mass imbalance of the East Antarctic Ice
      Sheet is likely to be small, but even its sign cannot yet be determined. Large
      sectors of ice in southeast Greenland, the Amundsen Sea Embayment of West
      Antarctica, and the Antarctic Peninsula are changing quite rapidly as a result of
      processes not yet understood.

PMID- 12202818
TI  - Air-snow interactions and atmospheric chemistry.
AB  - The presence of snow greatly perturbs the composition of near-surface polar air,
      and the higher concentrations of hydroxyl radicals (OH) observed result in a
      greater oxidative capacity of the lower atmosphere. Emissions of nitrogen oxides,
      nitrous acid, light aldehydes, acetone, and molecular halogens have also been
      detected. Photolysis of nitrate ions contained in the snow appears to play an
      important role in creating these perturbations. OH formed in the snowpack can
      oxidize organic matter and halide ions in the snow, producing carbonyl compounds
      and halogens that are released to the atmosphere or incorporated into snow
      crystals. These reactions modify the composition of the snow, of the interstitial
      air, and of the overlying atmosphere. Reconstructing the composition of past
      atmospheres from ice-core analyses may therefore require complex corrections and
      modeling for reactive species.

PMID- 12202819
TI  - Environmental change and Antarctic seabird populations.
AB  - Recent changes in Antarctic seabird populations may reflect direct and indirect
      responses to regional climate change. The best long-term data for high-latitude
      Antarctic seabirds (Adelie and Emperor penguins and snow petrels) indicate that
      winter sea-ice has a profound influence. However, some effects are inconsistent
      between species and areas, some in opposite directions at different stages of
      breeding and life cycles, and others remain paradoxical. The combination of
      recent harvest driven changes and those caused by global warming may produce
      rapid shifts rather than gradual changes.

PMID- 12202820
TI  - Left hemisphere cerebral specialization for babies while babbling.

PMID- 12202821
TI  - Controlled elimination of clathrin heavy-chain expression in DT40 lymphocytes.
AB  - We exploited the high rate of homologous recombination shown by the chicken B
      cell line DT40 to inactivate the endogenous alleles for clathrin heavy chain and
      replace them with human clathrin complementary DNA under the control of a
      tetracycline-regulatable promoter. Clathrin repression perturbed the activities
      of Akt-mediated and mitogen-activated protein kinase-mediated signaling pathways
      and induced apoptosis; this finding suggests that in DT40 cells clathrin helps to
      maintain the integrity of antiapoptotic survival pathways. We also describe a
      variant cell line in which these signaling pathways were unaffected by clathrin
      down-regulation. This variant cell line did not undergo apoptosis in the absence
      of clathrin and was used to examine the effects of clathrin depletion on membrane
      trafficking pathways. Receptor-mediated and fluid-phase endocytosis were both
      substantially inhibited, and transferrin-receptor recycling was modestly
      inhibited. Surprisingly, clathrin removal did not affect the morphology or
      biochemical composition of lysosomes.

PMID- 12202822
TI  - SynCAM, a synaptic adhesion molecule that drives synapse assembly.
AB  - Synapses, the junctions between nerve cells through which they communicate, are
      formed by the coordinated assembly and tight attachment of pre- and postsynaptic
      specializations. We now show that SynCAM is a brain-specific, immunoglobulin
      domain-containing protein that binds to intracellular PDZ-domain proteins and
      functions as a homophilic cell adhesion molecule at the synapse. Expression of
      the isolated cytoplasmic tail of SynCAM in neurons inhibited synapse assembly.
      Conversely, expression of full-length SynCAM in nonneuronal cells induced synapse
      formation by cocultured hippocampal neurons with normal release properties.
      Glutamatergic synaptic transmission was reconstituted in these nonneuronal cells
      by coexpressing glutamate receptors with SynCAM, which suggests that a single
      type of adhesion molecule and glutamate receptor are sufficient for a functional
      postsynaptic response.

PMID- 12202823
TI  - The mechanism of diamond nucleation from energetic species.
AB  - A model for diamond nucleation by energetic species (for example, bias-enhanced
      nucleation) is proposed. It involves spontaneous bulk nucleation of a diamond
      embryo cluster in a dense, amorphous carbon hydrogenated matrix; stabilization of
      the cluster by favorable boundary conditions of nucleation sites and hydrogen
      termination; and ion bombardment-induced growth through a preferential
      displacement mechanism. The model is substantiated by density functional tight
      binding molecular dynamics simulations and an experimental study of the structure
      of bias-enhanced and ion beam-nucleated films. The model is also applicable to
      the nucleation of other materials by energetic species, such as cubic boron
      nitride.

PMID- 12202824
TI  - Oxidation-resistant gold-55 clusters.
AB  - Gold nanoparticles ranging in diameter from 1 to 8 nanometers were prepared on
      top of silicon wafers in order to study the size dependence of their oxidation
      behavior when exposed to atomic oxygen. X-ray photoelectron spectroscopy showed a
      maximum oxidation resistance for "magic-number" clusters containing 55 gold
      atoms. This inertness is not related to electron confinement leading to a size
      induced metal-to-insulator transition, but rather seems to be linked to the
      closed-shell structure of such magic clusters. The result additionally suggests
      that gold-55 clusters may act as especially effective oxidation catalysts, such
      as for oxidizing carbon monoxide.

PMID- 12202825
TI  - Nanoparticles with Raman spectroscopic fingerprints for DNA and RNA detection.
AB  - Multiplexed detection of oligonucleotide targets has been performed with gold
      nanoparticle probes labeled with oligonucleotides and Raman-active dyes. The gold
      nanoparticles facilitate the formation of a silver coating that acts as a surface
      enhanced Raman scattering promoter for the dye-labeled particles that have been
      captured by target molecules and an underlying chip in microarray format. The
      strategy provides the high-sensitivity and high-selectivity attributes of gray
      scale scanometric detection but adds multiplexing and ratioing capabilities
      because a very large number of probes can be designed based on the concept of
      using a Raman tag as a narrow-band spectroscopic fingerprint. Six dissimilar DNA
      targets with six Raman-labeled nanoparticle probes were distinguished, as well as
      two RNA targets with single nucleotide polymorphisms. The current unoptimized
      detection limit of this method is 20 femtomolar.

PMID- 12202826
TI  - Fluidity of bound hydration layers.
AB  - We have measured the shear forces between solid surfaces sliding past each other
      across aqueous salt solutions, at pressures and concentrations typical of
      naturally occurring systems. In such systems the surface-attached hydration
      layers keep the compressed surfaces apart as a result of strongly repulsive
      hydration forces. We find, however, that the bound water molecules retain a shear
      fluidity characteristic of the bulk liquid, even when compressed down to films
      1.0 +/- 0.3 nanometer thick. We attribute this to the ready exchange (as opposed
      to loss) of water molecules within the hydration layers as they rub past each
      other under strong compression.

PMID- 12202827
TI  - Natural product terpenoids in Eocene and Miocene conifer fossils.
AB  - Numerous saturated and aromatic hydrocarbons, but not polar compounds,
      originating from plants and microorganisms (biomarkers) have been reported in
      sediments, coals, and petroleum. Here we describe natural product terpenoids
      found in two fossil conifers, Taxodium balticum (Eocene) and Glyptostrobus
      oregonensis (Miocene). A similar terpenoid pattern is also observed in extant
      Taxodium distichum. The preservation of characteristic terpenoids (unaltered
      natural products) in the fossil conifers supports their systematic assignment to
      the Cypress family (Cupressaceae sensu lato). The results also show that fossil
      conifers can contain polar terpenoids, which are valuable markers for
      (paleo)chemosystematics and phylogeny.

PMID- 12202828
TI  - Global biodiversity, biochemical kinetics, and the energetic-equivalence rule.
AB  - The latitudinal gradient of increasing biodiversity from poles to equator is one
      of the most prominent but least understood features of life on Earth. Here we
      show that species diversity can be predicted from the biochemical kinetics of
      metabolism. We first demonstrate that the average energy flux of populations is
      temperature invariant. We then derive a model that quantitatively predicts how
      species diversity increases with environmental temperature. Predictions are
      supported by data for terrestrial, freshwater, and marine taxa along latitudinal
      and elevational gradients. These results establish a thermodynamic basis for the
      regulation of species diversity and the organization of ecological communities.

PMID- 12202829
TI  - Geographic range size and determinants of avian species richness.
AB  - Geographic patterns in species richness are mainly based on wide-ranging species
      because their larger number of distribution records has a disproportionate
      contribution to the species richness counts. Here we demonstrate how this effect
      strongly influences our understanding of what determines species richness. Using
      both conventional and spatial regression models, we show that for sub-Saharan
      African birds, the apparent role of productivity diminishes with decreasing range
      size, whereas the significance of topographic heterogeneity increases. The
      relative importance of geometric constraints from the continental edge is
      moderate. Our findings highlight the failure of traditional species richness
      models to account for narrow-ranging species that frequently are also threatened.

PMID- 12202830
TI  - Hierarchical organization of modularity in metabolic networks.
AB  - Spatially or chemically isolated functional modules composed of several cellular
      components and carrying discrete functions are considered fundamental building
      blocks of cellular organization, but their presence in highly integrated
      biochemical networks lacks quantitative support. Here, we show that the metabolic
      networks of 43 distinct organisms are organized into many small, highly connected
      topologic modules that combine in a hierarchical manner into larger, less
      cohesive units, with their number and degree of clustering following a power law.
      Within Escherichia coli, the uncovered hierarchical modularity closely overlaps
      with known metabolic functions. The identified network architecture may be
      generic to system-level cellular organization.

PMID- 12202831
TI  - Gated visual input to the central auditory system.
AB  - The central auditory system translates sound localization cues into a map of
      space guided, in part, by visual experience. In barn owls, this process takes
      place in the external nucleus of the inferior colliculus (ICX). However, to date,
      no trace of visual activity has been observed in this auditory nucleus. Here we
      show that strong visual responses, which are appropriate to guide auditory
      plasticity, appear in the ICX when inhibition is blocked in the optic tectum.
      Thus, visual spatial information is gated into the auditory system by an
      inhibitory mechanism that operates at a higher level in the brain.

PMID- 12202832
TI  - Medulloblastoma growth inhibition by hedgehog pathway blockade.
AB  - Constitutive Hedgehog (Hh) pathway activity is associated with initiation of
      neoplasia, but its role in the continued growth of established tumors is unclear.
      Here, we investigate the therapeutic efficacy of the Hh pathway antagonist
      cyclopamine in preclinical models of medulloblastoma, the most common malignant
      brain tumor in children. Cyclopamine treatment of murine medulloblastoma cells
      blocked proliferation in vitro and induced changes in gene expression consistent
      with initiation of neuronal differentiation and loss of neuronal stem cell-like
      character. This compound also caused regression of murine tumor allografts in
      vivo and induced rapid death of cells from freshly resected human
      medulloblastomas, but not from other brain tumors, thus establishing a specific
      role for Hh pathway activity in medulloblastoma growth.

PMID- 12202833
TI  - Structural basis of transcription activation: the CAP-alpha CTD-DNA complex.
AB  - The Escherichia coli catabolite activator protein (CAP) activates transcription
      at P(lac), P(gal), and other promoters through interactions with the RNA
      polymerase alpha subunit carboxyl-terminal domain (alphaCTD). We determined the
      crystal structure of the CAP-alphaCTD-DNA complex at a resolution of 3.1
      angstroms. CAP makes direct protein-protein interactions with alphaCTD, and
      alphaCTD makes direct protein-DNA interactions with the DNA segment adjacent to
      the DNA site for CAP. There are no large-scale conformational changes in CAP and
      alphaCTD, and the interface between CAP and alphaCTD is small. These findings are
      consistent with the proposal that activation involves a simple "recruitment"
      mechanism.

PMID- 12202834
TI  - Identification of a potential ejaculation generator in the spinal cord.
AB  - We tested the significance of a population of lumbar spinothalamic cells for male
      sexual behavior in rats. These cells are positioned to relay ejaculation-related
      signals from reproductive organs to the brain, and they express neurokinin-1
      receptors. Ablation of these neurons by the selective toxin SSP-saporin resulted
      in a complete disruption of ejaculatory behavior. In contrast, other components
      of sexual behavior remained intact. These results suggest that this population of
      spinothalamic cells plays a pivotal role in generation of ejaculatory behavior
      and may be part of a spinal ejaculation generator.

PMID- 12202835
TI  - Ethnic variation in C-reactive protein: UK resident Indo-Asians compared with
      Caucasians.
AB  - BACKGROUND: The increased prevalence of coronary heart disease (CHD) in UK
      resident Indo-Asians is unexplained by the traditional cardiovascular risk
      factors of dyslipidaemia, hypertension, smoking and diabetes mellitus. C-reactive
      protein (CRP) has been implicated in the pathogenesis of CHD but the data on
      ethnic variation in CRP is conflicting. We therefore investigated whether CRP
      could help explain the increased prevalence of CHD in Indo-Asians. DESIGN AND
      METHODS: We measured CRP, using a highly sensitive assay, in 102 men (63
      Caucasians and 39 Indo-Asians) and 89 women (58 Caucasians and 31 Indo-Asians).
      All subjects, aged between 40 and 70 years, were nondiabetic and nonsmokers.
      RESULTS: Serum CRP correlated (P < 0.05) positively with coronary risk. Serum HDL
      cholesterol concentrations were lower (P<0.05) in Indo-Asian women when compared
      with Caucasian women, but otherwise the ethnic groups were matched for calculated
      coronary risk and cardiovascular risk factors. Serum CRP concentrations were
      similar in Indo-Asians (women 2.29 (1.52) mg/l [mean (SD)]; men 1.77 (1.46) mg/l)
      and Caucasians (women 2.23 (1.54) mg/l; men 1.94 (1.45) mg/l). CONCLUSIONS:
      Altered CRP concentrations does not appear to be implicated in the increased
      prevalence of CHD in UK resident Indo-Asians.

PMID- 12202836
TI  - Cerebrovascular disease in Italy and Europe: it is necessary to prevent a
      'pandemia'.
AB  - In Italy and Europe, strokes are the third most common cause of death and
      resulting invalidity. In the ever-increasing 80-years-old-and-over people,
      strokes become more serious due to the clinical presentation during the acute
      phase and the ten-times higher mortality, but also in relation to the twice as
      high resulting disability as for younger subjects. However, stroke prevention is
      possible both through correct behavioural habits and pharmacological means.
      Besides the well-known preventive effects of an adequate anti-hypertensive, anti
      diabetic and/or anti-aggregant/anti-coagulant therapy, there are increasing
      evidences of the effectiveness of the anti-hypercholesterolemic therapy in stroke
      prevention. Moreover, a great part of the risk factors for the cerebrovascular
      disease coincides with those for cardiovascular disease, for which the correction
      of the former automatically involves a reduction in incidence of both
      pathologies. In this context, a statin's rational use can therefore represent an
      important tool for the combined prevention of the two pathologies. Finally,
      different hypotheses link the origin of Alzheimer's disease to that of
      progressive cerebrovascular dementia caused by cerebral microcirculation damage.
      It is plausible that the application of a suitable early prevention of the
      cerebrovascular pathology could bring to a more late slatentisation and less
      serious demonstrations of Alzheimer's disease, when this is destined to develop.

PMID- 12202837
TI  - Overall cardiovascular risk still ignored in general practice care of
      hypertension.
AB  - BACKGROUND: Recent guidelines for the management of arterial hypertension have
      emphasized the importance of total cardiovascular risk for setting the blood
      pressure (BP) goal to be achieved and the intensity with which it should be
      pursued. DESIGN: To assess the degree of BP control in hypertensives receiving
      long-term antihypertensive treatment according to the presence of major
      cardiovascular risk factors or diseases and the level of individual total
      cardiovascular risk, a large sample of general practitioners throughout Italy had
      to evaluate a random sample of their hypertensive patients. METHODS: A clinical
      history was collected for each patient and BP was measured three times using a
      reliable automatic instrument. To stratify the cardiovascular risk we used the
      criteria suggested by the 1999 WHO-ISH guidelines. RESULTS: Among the 1204
      patients recruited (mean age 64.2 +/- 11.4 years, 663 females), only 399 patients
      (33.1%) had a BP lower than 140/90 mmHg. Except for male sex and previous
      myocardial infarction, the concomitant presence of major cardiovascular risk
      factors or diseases was never associated to a better control of hypertension. BP
      control was unrelated to individual overall cardiovascular risk: BP was < 140/90
      mmHg respectively in 44.0, 37.7, 33.5 and 42.1% (P for trend = 0.54) of people
      aged less than 65 years with low, medium, high and very high risk and in 27.7,
      25.9 and 27.1% (P for trend = 0.91) of people aged more than 65 years at medium,
      high and very high risk. CONCLUSIONS: BP control in Italian hypertensives is
      still unsatisfactory, even in patients at high and very high cardiovascular risk.

PMID- 12202838
TI  - Depressive symptoms predict 12-month prognosis in elderly patients with acute
      myocardial infarction.
AB  - BACKGROUND: Several studies have associated depressive symptoms with an increased
      risk for cardiac events after the onset of acute myocardial infarction (AMI). The
      aim of the present study is to investigate the impact of the depressive symptoms
      on prognosis of the elderly patients with AMI. METHOD: Depression was assessed in
      consecutive patients with AMI (n = 1042; mean age 63 +/- 11 years) using the Zung
      Self-Rating Depression Scale (SDS). Patient with a score > or = 40 was classified
      as having depressive symptoms. Cardiac events (cardiac death, nonfatal re-MI,
      coronary angioplasty or bypass surgery, readmission for heart failure, unstable
      angina, or uncontrolled arrhythmia) were examined during 12 months follow-up
      period. RESULTS: Depressive symptoms were observed in 438 patients (42.0%).
      Prevalence of depression was not dependent of age (P = 0.60) and gender (P =
      0.91). The rate of cardiac events was 31.2% per year in patients with depressive
      symptoms whereas 23.9% per year in patients without depressive symptoms. Multiple
      logistic regression analyses showed that depression was significantly associated
      with 1-year cardiac events (odds ratio 1.41, 95% CI 1.03 to 1.92, P = 0.03) after
      controlling for age, gender, severity of myocardial infarction, coronary risk
      factors, e.g. hypertension, diabetes mellitus and smoking habits. Depression was
      a significant risk factor for the cardiac events (log rank, P = 0.02) in the
      elderly patients (> or = 65 years old, 501 patients). However, the association of
      depression with cardiac events in the young patients (< 65 years old, 541
      patients) was not statistically significant (P = 0.11). CONCLUSION: Depression
      after AMI is a significant predictor of 1-year cardiac events for Japanese
      population, and its presence augments the risk especially in the elderly
      patients.

PMID- 12202839
TI  - Tobacco use in South Africans during 1998: the first demographic and health
      survey.
AB  - OBJECTIVE: To determine smoking patterns in South Africa, and to identify groups
      requiring culturally appropriate smoking cessation programmes. METHODS: A random
      sample of 13,826 people (> 15 years), was interviewed to identify tobacco use
      patterns and respiratory symptoms. Peak expiratory flow rates were measured.
      Multinomial regression analyses identified sociodemographic factors related to
      tobacco use, and the latter's association with respiratory conditions. RESULTS:
      In 1998, 24.6% adults (44.2% of males and 11.0% of females) smoked regularly.
      Coloured women had a higher rate (39%) than African women (5.4%). About 24% of
      the regular smokers had attempted to quit, with only 9.9% succeeding. African
      women (13.2%) used smokeless tobacco more frequently than others. Of the
      nonsmokers 28% and 19% were exposed to environmental tobacco smoke in their homes
      and workplaces, respectively. The regression analysis showed that the demographic
      characteristics of light smokers (1-14 tobacco equivalents per day) and heavy
      smokers (> or = 15 tobacco equivalents per day) differed. Light smoking occurred
      significantly more frequently in the poorest, least educated and urban people.
      The relative risk for light smoking was 18 in Coloured women compared with
      African women. Heavy smoking occurred most frequently in the highest educated
      group. A dose-response was observed between the amount smoked and the presence of
      respiratory diseases. CONCLUSIONS: Smoking in South Africa is decreasing and
      should continue with the recently passed tobacco control legislation. Culturally
      appropriate tobacco cessation programmes for the identified target groups need to
      be developed.

PMID- 12202841
TI  - Vascular oxidative stress and antioxidant protection in atherosclerosis: what do
      the clinical trials say?

PMID- 12202840
TI  - Smoking, low density lipoprotein cholesterol, fibrinogen and myocardial
      infarction before 41 years of age: a Danish case-control study.
AB  - BACKGROUND: Of major coronary risk factors, smoking and total cholesterol were
      significant in a previous Danish case-control study of myocardial infarction at a
      young age. OBJECTIVE: To determine whether smoking was an important coronary risk
      factor in the context of new and major anthropometric and biochemical risk
      factors for myocardial infarction in individuals less than 41 years of age.
      METHODS: A prevalence hospital-based matched case-control study of young
      individuals. We selected 22 Caucasian cases and 24 Caucasian controls without
      coronary heart disease matching for age and gender and studied a series of major
      coronary risk factors and newer anthropometric and biochemical variables.
      RESULTS: In conditional univariate logistic regression analyses, the following
      factors were significantly associated with the coronary risk: family history,
      social class, smoking, intraabdominal adipose tissue area as percentage of total
      abdominal adipose tissue area on a CT scan, glycosylated haemoglobin level,
      systolic blood pressure, total cholesterol, low density lipoprotein (LDL)
      cholesterol, homocysteine, and fibrinogen levels (P < 0.05). However, in multiple
      conditional logistic regression analyses, only smoking, LDL cholesterol, and
      fibrinogen levels remained significant. Ten cases (46%) and none of the 24
      controls were smokers with a LDL cholesterol level 4.5 mmol/l and a fibrinogen
      level 3.7 g/l (P = 0.0003, Fisher's exact test). CONCLUSION: Out of a series of
      major and newer coronary risk factors in young Western Caucasians, smoking, and
      levels of LDL cholesterol, and fibrinogen were independent significant coronary
      risk factors. The findings need to be validated in prospective studies.

PMID- 12202842
TI  - Global initiative for chronic obstructive lung disease.

PMID- 12202843
TI  - The surveillance of cholesterol management in the cardiac rehabilitation setting.
AB  - PURPOSE: To evaluate the secondary prevention of coronary heart disease in the
      cardiac rehabilitation setting by quantifying the percentage of patients on lipid
      lowering therapy, the percentage of patients who have received diet counseling,
      and the percentage of patients with a lipid panel documented by discharge.
      METHODS: The Web-based database of the Wisconsin Society for Cardiovascular and
      Pulmonary Rehabilitation, representing 1477 patients, was examined for patient
      outcomes. A survey was sent to programs to assess the processes in place to
      assist patients in managing cholesterol and reaching a low-density lipoprotein
      (LDL-C) goal of less than 100 mg/dL. RESULTS: Most patients were taking
      cholesterol medications (median, 70.9%; 95% confidence interval [CI], 63.9-80.9).
      A minority of patients had an LDL-C at the goal level (median, 42.6%; 95% CI,
      27.7-58.6), and a few patients had received individual dietary counseling from a
      registered dietitian (median, 17.9%; 95% CI, 4.8-56.2). The survey indicated that
      although all programs made an effort to determine cholesterol levels at cardiac
      rehabilitation entry, only one half of the programs required a lipid panel at
      discharge also. CONCLUSIONS: There is a high degree of variation among cardiac
      rehabilitation programs in terms of surveillance and treatment of dyslipidemias
      for patients with coronary heart disease.

PMID- 12202844
TI  - A report card on remodeling cardiac rehabilitation into secondary prevention
      programs: not making the grade.

PMID- 12202845
TI  - Patient characteristics and outcomes of cardiac rehabilitation.
AB  - PURPOSE: To investigate changes in physical fitness and psychological
      characteristics of patients after cardiac rehabilitation, and to assess
      predictors of defaulting from the program. METHODS: A prospective study of 1902
      consecutive patients admitted to a community-based, hospital-linked cardiac
      rehabilitation program was conducted over a period of 6 years and 7 months. The
      cardiac rehabilitation program centered on a 2-to 6-month circuit training course
      with education, stress management, relaxation, and risk factor monitoring. Before
      and after the program, measures of physical fitness and of hospital anxiety and
      depression were performed. RESULTS: The course was completed by 1443 patients
      (76%), with 240 patients (13%) defaulting. For those who completed the course,
      peak oxygen consumption per minute increased by 3.2 mL/min/kg (95% confidence
      interval [CI], 3.1-3.4) or 19% (95% CI, 17.7%-20.3%). According to the hospital
      anxiety and depression scores, anxiety fell by 1.1 (95% CI, -1.3 to -0.98) and
      depression by 1.3 (95% CI, -1.4 to -1.2). The main predictors of defaulting were
      depression (patients with depression were twice as likely to default as
      nondepressed patients) and diagnosis (patients who had experienced angina or
      percutaneous transluminal coronary angioplasty were twice as likely to default as
      those who had experienced infarct or coronary artery bypass graft). CONCLUSIONS:
      The identification of depressed coronary patients known to be at increased risk
      should be a priority for cardiac rehabilitation coordinators. Every effort should
      be made to keep them in the cardiac rehabilitation program.

PMID- 12202846
TI  - Issues in predicting adherence to cardiac rehabilitation.

PMID- 12202847
TI  - A representative study of cardiac rehabilitation activities in European Union
      Member States: the Carinex survey.
AB  - PURPOSE: Empirical data on the level and nature of service delivery in cardiac
      rehabilitation (CR) in Europe are unavailable. Such information would facilitate
      service development across European Union (EU) Member States. A first EU-wide
      postal survey to provide baseline data was conducted. METHODS: Organizations
      providing CR in 1995 were identified for 13 of 15 EU states (all except
      Luxembourg and Denmark). Using the World Health Organization definitions, 454
      phase II (medium-term recovery after hospital release) and 383 phase III (long
      term maintenance) centers were contacted in the relevant language. Staffing,
      content, duration, cost, and safety aspects of CR were queried. RESULTS: Response
      rates were 57% (phase II) and 56% (phase III). Replies illustrate consistency
      across the EU; for instance, in having exercise as a core component of phase II
      programs. They also exemplify the diversity of services, particularly in phase
      III. The multidisciplinary aspect of CR is less developed in phase III. From this
      survey it is possible to make general estimates of the level of CR service
      coverage across EU States. Fewer than 50% of patients eligible to participant do
      so in most countries, with services in particularly short supply in countries
      with the greatest cardiovascular burden. CONCLUSION: Many cardiac patients who
      could benefit from CR, an evidence-based treatment, do not participate in such
      programs. This survey provides important baseline and EU comparison data to
      monitor patterns of service development in the future.

PMID- 12202848
TI  - Relationship between the Minnesota Living With Heart Failure Questionnaire and
      key ventilatory expired gas measures during exercise testing in patients with
      heart failure.
AB  - PURPOSE: This study assessed the relationship between the Minnesota Living With
      Heart Failure Questionnaire (MLWHFQ) and key ventilatory expired gas measures
      during a symptom-limited exercise test in the heart failure (HF) population.
      Specifically, is there evidence to indicate that perceived quality of life (QOL)
      influences exercise performance independent of physiologic function in the HF
      population? METHODS: Thirty-one subjects (21 male/10 female), diagnosed with
      compensated HF, underwent exercise testing and completed the MLWHFQ. Mean age and
      left ventricular ejection fraction were 52.8 years and 27.2%, respectively.
      Partial correlation, controlling for age and sex, assessed the relationship
      between MLWHFQ (overall and subscores) and key ventilatory expired gas measures.
      Intraclass correlation coefficient (ICC) analysis was used to determine
      reliability of the MLWHFQ. RESULTS: MLWHQ overall score (mean = 38.9, median =
      36.0), physical subscore (mean = 14.8, median = 16.0), and
      psychosocial/symptomatology subscore (mean = 24.1, median = 19.0), were
      significantly correlated (P < or =.05) with peak oxygen consumption (VO2). The
      relationship between MLWHFQ and the minute ventilation-carbon dioxide production
      (VE/VCO2) slope was, however, not significant. ICC analysis revealed high
      reliability (0.95) for the MLWHFQ. CONCLUSIONS: The MLWHFQ demonstrates a
      significant relationship with peak VO2, a measure whose validity is dependent
      upon subject effort. VE/VCO2 slope, which is independent of subject effort and
      therefore potentially a better predictor of true physiologic function, does not
      appear to have a relationship with perceived QOL. These findings have
      implications for how the MLWHFQ is assessed, related to an exercise test, and
      used during clinical practice.

PMID- 12202849
TI  - Predictors of quality of life in long-term recipients of implantable cardioverter
      defibrillators.

PMID- 12202850
TI  - Reliability of isokinetic strength and aerobic power testing for patients with
      chronic heart failure.
AB  - PURPOSE: The objective of this study was to assess the reliability of testing
      skeletal muscle strength and peak aerobic power in a clinical population of
      patients with chronic heart failure (CHF). METHODS: Thirty-three patients with
      CHF (New York Heart Association (NYHA) Functional Class 2.3 +/- 0.5; left
      ventricular ejection fraction 27% +/- 7%; age 65 +/- 9 years; 28:5 male-female
      ratio) underwent two identical series of tests (T1 and T2), 1 week apart, for
      strength and endurance of the muscle groups responsible for knee
      extension/flexion and elbow extension/flexion. The patients also underwent two
      graded exercise tests on a bicycle ergometer to measure peak oxygen consumption
      (VO(2peak)). Three months later, 18 of the patients underwent a third test (T3)
      for each of the measures. Means were compared using MANOVA with repeated measures
      for strength and endurance, and ANOVA with repeated measures for VO(2peak).
      RESULTS: Combining data for all four movement patterns, the expression of
      strength increased from T1 to T2 by 12% +/- 25% (P <.001; intraclass correlation
      coefficient [ICC] = 0.89). Correspondingly, endurance increased by 13% +/- 23% (P
      =.004; ICC = 0.87). Peak oxygen consumption was not significantly different (16.2
      +/- 0.8 and 16.1 +/- 0.8 mL.kg(-1).min(-1) for T1 and T2, respectively; P =.686;
      ICC = 0.91). There were no significant differences between T2 and T3 for strength
      (2% +/- 17%; P =.736; ICC = 0.92) or muscle endurance (-1% +/- 15%; P =.812; ICC
      = 0.96), but VO(2peak) decreased from 16.7 +/- 1.2 to 14.9 +/- 0.9 mL.kg(-1).min(
      1) (-10% +/- 18%; P =.021; ICC = 0.89). CONCLUSIONS: These data suggest that in a
      population of patients with CHF, a familiarization trial for skeletal muscle
      strength testing is necessary. Although familiarization is not required for
      assessing oxygen consumption as a single measurement, VO(2peak) declined markedly
      in the 3-month period for which these patients were followed. Internal
      consistency within patients was high for the second and third strength trials and
      the first and second tests of VO(2peak).

PMID- 12202851
TI  - The acute effects of noninvasive ventilatory support during exercise on exercise
      endurance and dyspnea in patients with chronic obstructive pulmonary disease: a
      systematic review.
AB  - PURPOSE: The objective of this study was to review studies systematically, in
      which the acute effects of noninvasive ventilatory support (NIVS) during exercise
      were evaluated in patients with chronic obstructive pulmonary disease (COPD). In
      addition, a quantitative analysis was performed on the effects of NIVS on
      exertional dyspnea and exercise endurance. METHODS: Literature was searched in
      electronic databases, and by scanning lists of references of studies and abstract
      books of annual congresses of the American Thoracic Society and European
      Respiratory Society. Preliminary data of a study by our own group into the
      effects of NIVS on exercise endurance in patients with COPD were added. The
      systematic review was carried out on the basis of a validated methodological
      screening list. For the quantitative analysis, Glass delta of individual studies
      were pooled to aggregate a summary effect size. RESULTS: Fifteen studies were
      identified. Seven of these studies met the inclusion criteria, including a total
      of 65 patients with COPD. The methodological quality of the included studies
      varied from 31% to 54% of the maximum score of 13 points. Statistically
      significant summary effect sizes were found in the analysis of exertional dyspnea
      (P <.05) as well as in the analysis of exercise endurance (P <.001), indicating
      improvements in these outcomes in favor of NIVS. CONCLUSIONS: The present
      systematic review suggests that NIVS during exercise may acutely reduce
      exertional dyspnea and improve exercise endurance, in patients with COPD.

PMID- 12202852
TI  - Criterion validity of the Duke Activity Status Index for assessing functional
      capacity in patients with chronic obstructive pulmonary disease.
AB  - PURPOSE: This study evaluated the concurrent criterion validity of the Duke
      Activity Status Index (DASI) with respect to standard physiologic work capacity
      indices in patients with chronic obstructive pulmonary disease (COPD) and
      compared its performance with similar surrogates. METHODS: 119 patients with
      moderate to severe COPD (86 men, 33 women) completed medical and smoking
      histories, physical examination, pulmonary function testing (PFT), cycle
      ergometry (CE), arm ergometry (AE), and 6-minute walk distance (6MWD), DASI, the
      Sickness Impact Profile-68 (SIP-68) and the Chronic Respiratory Disease
      Questionnaire (CRDQ). Correlation methods were used to assess the validity of the
      potential surrogates DASI and the domain scores for SIP-68 and CRDQ, with the
      standards CE, AE, PFT, and 6MWD (as a standard). RESULTS: The mean DASI score was
      33.4 +/- 13.0. Significant Pearson correlations (P <.01) were observed between
      the DASI and PFT outcomes maximum voluntary ventilation (r =.28); peak expiratory
      flow (r =.21); diffusion capacity of lung for carbon monoxide (r =.30). For CE,
      the correlations with DASI were oxygen consumption (VO(2))(r =.34); minute
      ventilation (r =.25); watts (r =.37). For AE, the correlations with DASI were
      VO(2) (r=.38); watts (r =.47). For 6MWD, the correlation was r =.53. Higher
      correlations were obtained for the distance completed during the first minute of
      the 6MWD and ergometric indices as well as DASI scores: watts(AE) (r =.39);
      VO(2AE) (r =.45); watts(CE) (r =.50); VO(2CE) (r =.44). Correlation coefficients
      for all SIP-68 and CRDQ domain and total scores were lower than corresponding
      correlations obtained for the DASI. Regression analysis demonstrated that the
      DASI and 6MWD were important (P <.05) for predicting VO(2) or work for CE while
      DASI and SIP range or CRDQ dyspnea entered for AE, when gender, age, BMI, and the
      FEV1 were forced into the model. In forward stepwise analyses, DASI entered first
      for AE, and 6MWD entered first for CE. The DASI was selected in 3 of 4 models
      with R(2) values ranging from.47 to.70. SIP-68 and CRDQ subscores were
      significant as additional predictors. CONCLUSIONS: DASI has high criterion
      validity for predicting CE and/or AE outcomes in the COPD population. It is
      warranted in addition to the 6MWD, and its predictive significance and simplicity
      recommends it over several other self-administered instruments for evaluating
      functional capacity.

PMID- 12202853
TI  - Family-focused pediatrics: a primary care family systems approach to psychosocial
      problems.

PMID- 12202855
TI  - Developmental and neurologic outcomes late after neonatal corrective surgery.

PMID- 12202856
TI  - Commentary on sentinel lymph node identification with technetium-99m tin colloid
      in non-small cell lung cancer.

PMID- 12202857
TI  - Off-pump coronary bypass: Is it for everyone?

PMID- 12202858
TI  - The endothelin antagonist BQ123 reduces pulmonary vascular resistance after
      surgical intervention for congenital heart disease.
AB  - OBJECTIVE: Postoperative pulmonary hypertension in children after surgical
      intervention for congenital heart disease has been attributed to failure of the
      pulmonary endothelium to provide adequate vasodilation. Although we have shown
      that the impaired vasodilatory component attributable to the l-arginine-nitric
      oxide pathway is almost completely reversible, a nonrestorable component
      persists, implying an additional vasoconstrictive mechanism in postoperative
      pulmonary endothelial dysfunction. In this study of children after surgical
      intervention for congenital heart disease, we measured endothelin-1 levels and
      used BQ123, a selective endothelin-A receptor antagonist, together with inhaled
      nitric oxide to discriminate dysfunctional pulmonary endothelial vasodilation
      from endothelin-mediated pulmonary vasoconstriction. METHODS: All children were
      examined early after surgical intervention in the intensive care unit. Pulmonary
      vascular resistance (with respiratory mass spectrometry), as well as arterial and
      venous endothelin-1 levels (measured by means of a quantitative enzyme-linked
      immunosorbent assay), were determined in 7 children (age range, 3.3-13.7 months;
      median age, 6.3 months) with intracardiac shunting defects at baseline and during
      ventilation with a fraction of inspired oxygen of 0.65, with additional BQ123
      (0.1 mg/kg infused over 20 minutes), and with inhaled nitric oxide (20 ppm).
      RESULTS: Pulmonary vascular resistance decreased from 7.7 +/- 3.4 at baseline to
      6.1 +/- 2.8 Woods units. m(-2) (P =.022) at a fraction of inspired oxygen of 0.65
      and to 4.7 +/- 2.7 Woods units. m(-2) (P =.013) during BQ123 infusion. Inhaled
      nitric oxide had no further effect on pulmonary vascular resistance. Left atrial
      endothelin-1 levels (1.35-5.12 pg/mL; mean, 2.4 pg/mL) correlated significantly
      with the decrease in pulmonary vascular resistance in response to BQ123 infusion
      (r(2) = 0.89, P =.003). CONCLUSION: Postoperative elevation of pulmonary vascular
      resistance in children after surgical intervention for congenital heart disease
      is responsive to endothelin-A blockade with BQ123. Increased levels of endothelin
      1 predict the response to this therapy, which might become an important addition
      to the clinical armamentarium in postoperative pulmonary hypertensive disease.

PMID- 12202859
TI  - Septation of the single ventricle: revisited.
AB  - BACKGROUND: Septation of a single ventricle into 2 functioning ventricles can
      provide an alternative to the Fontan operation. However, early experiences with
      septation reported unacceptable morbidity and mortality. The present study
      selected only those patients with large volume-overloaded hearts, 2 well
      functioning atrioventricular valves, and an absence of severe outlet obstruction.
      Early and intermediate outcomes are evaluated. METHODS AND RESULTS: Between June
      1990 and March 1999, 11 patients underwent septation in 1 or 2 stages. Diagnoses
      of the patients included double-inlet left ventricle in 9, double-inlet right
      ventricle in 1 patient, and indeterminate ventricle in 1 patient. Five had l
      transposition and 3 had d-transposition of the great arteries. Six had septation
      as 1 stage, 5 as planned 2-stage operations (2/5 completed). The median age for
      septation in 1 stage was 2.1 years (range 4 months to 5.8 years); for 2 stages,
      the median age was 7.2 months (range 3 to 14 months). Median follow-up time was
      2.3 years. Eight of 11 patients survived (73%), with 2 early deaths and 1 late
      death. Seven of the 8 survivors have undergone complete septation (5 as single
      stage, 2 as 2 stages). Complications included surgically induced complete
      atrioventricular block in 1 patient and significant residual ventricular septal
      defects in another. Qualitatively, left ventricular function by echocardiography
      is normal in all patients, whereas right ventricular function is mildly decreased
      in 1 patient. All patients are clinically well. CONCLUSION: The septation
      procedure for single ventricle hearts may be a reasonable alternative to the
      Fontan operation in selected patients.

PMID- 12202860
TI  - Long-term neurodevelopmental outcomes in school-aged children after neonatal
      arterial switch operation.
AB  - OBJECTIVE: Neurodevelopmental status of children between 8 and 14 years of age
      after neonatal arterial switch operation for transposition of the great arteries
      has not previously been systematically evaluated. METHODS: Within a longitudinal
      study, 60 unselected children operated on as neonates with combined deep
      hypothermic circulatory arrest and low-flow cardiopulmonary bypass were
      reevaluated at the age of 7.9 to 14.3 years (mean +/- SD 10.5 +/- 1.6 years).
      Clinical neurologic status and standardized tests to assess gross motor function,
      intelligence, acquired abilities, language, and speech were carried out, and the
      results were related to preoperative, perioperative, and postoperative status, to
      management, and to neurodevelopmental status at a mean age of 5.4 years. RESULTS:
      Neurologic and speech impairments were evidently more frequent (27% and 40%,
      respectively) than in the general population. Intelligence and socioeconomic
      status were not different (P =.29 and P =.11), whereas motor function, acquired
      abilities, and language were reduced (P < or =.04 for each). Overall rate of
      developmental impairment in one or more domains was 55%, compared with 26% at age
      5.4 years. Multivariable analysis showed that severe preoperative acidosis and
      hypoxia predicted reduced motor function (mean deficit 52.7 points, P <.001),
      whereas longer bypass duration predicted both neurologic (odds ratio per 10
      minutes of bypass duration 1.8, P =.04) and speech (odds ratio per 10 minutes of
      bypass duration 1.9, P =.02) dysfunction, and perioperative and postoperative
      cardiocirculatory insufficiency predicted neurologic (odds ratio 6.5, P =.04) and
      motor (mean deficit 6.8 points, P =.03) dysfunction. CONCLUSIONS: The neonatal
      arterial switch operation with combined circulatory arrest and low-flow bypass is
      associated increasingly with age, with reduced neurodevelopmental outcome but not
      with cognitive dysfunction. In our experience, the risk of long-term
      neurodevelopmental impairment after neonatal corrective cardiac surgery is
      related to deleterious effects of the global perioperative management and to
      special adverse effects of prolonged bypass duration. Severe preoperative
      acidosis and hypoxia and postoperative hemodynamic instability must be considered
      as important additional risk factors.

PMID- 12202861
TI  - Surgical options and results of repeated aortic root replacement for failed
      aortic allografts placed in childhood.
AB  - OBJECTIVES: This report reviews our experience with repeated aortic root
      replacement after failure of cryopreserved aortic allografts placed during
      childhood and compares replacement with aortic allografts, pulmonary autografts,
      and mechanical valved conduits in these patients. METHODS: This was a
      retrospective analysis of all such patients from 1986 through May 2001. RESULTS:
      There were 25 operations (11 aortic allografts, 9 pulmonary autografts, and 5
      mechanical valved conduits) among 23 patients. The mean time to reoperation was
      6.3 years. There were 2 in-hospital deaths (8%, 1 patient with a pulmonary
      autograft and 1 with a mechanical valved conduit). There were 2 early nonfatal
      valve-related events (1 patient with an aortic allograft and 1 with a pulmonary
      autograft). There were no late valve-related deaths and 2 late non-valve-related
      deaths of patients with aortic allografts placed. No variable predicted early
      death or early valve-related event. No differences in preoperative
      characteristics, hospital variables, early outcomes, or late outcomes were
      detected among the groups. Overall, 19 patients are alive (18 in New York Heart
      Association functional class I and 1 in New York Heart Association functional
      class III) at a mean follow-up of 49 months. Two late aortic allograft failures
      necessitated reoperation. All patients with successful pulmonary autografts had
      excellent autograft function at a mean follow-up of 68 months. All early
      survivors with mechanical valved conduits are alive and free of valve-related
      events (mean follow-up 71 months). Five-year freedoms from valve-related death or
      event (Kaplan-Meier) were 84% for all patients, 91% for aortic allografts, 78%
      for pulmonary autografts, and 80% for mechanical valved conduits (no
      statistically significant group differences by log-rank test). CONCLUSIONS:
      Replacement of cryopreserved aortic root allografts placed during childhood is
      safe. Five-year pulmonary autograft durability is excellent, although the risk of
      early failure may be increased. Differences in 5-year conduit longevity were not
      detectable.

PMID- 12202862
TI  - The beneficial vortex and best spatial arrangement in total extracardiac
      cavopulmonary connection.
AB  - OBJECTIVE: Total extracardiac cavopulmonary connection is an established
      procedure, but the best spatial arrangement remains controversial. On the basis
      of our clinical experience with total extracardiac cavopulmonary connection, we
      performed quantitative and qualitative flow analysis on total extracardiac
      cavopulmonary connection models simulating the two most frequent arrangements
      applied to our patients to determine the most favorable hydrodynamic pattern.
      METHODS: We selected two main groups among 110 patients who underwent total
      extracardiac cavopulmonary connection, those with left-sided inferior vena cava
      anastomosis (type 1) and those with facing superior and inferior vena cava
      anastomoses (type 2). Blown-glass total extracardiac cavopulmonary connection
      phantom models were constructed on the basis of nuclear magnetic resonance and
      angiographic images. Flow measurements were performed with a Nd:YAG Q-switched
      laser and a particle imaging velocimetry system. A power dissipation study and a
      finite-element numeric simulation were also carried out. RESULTS: When applying
      superior and inferior vena caval flow proportions of total systemic venous return
      of 40% and 60%, respectively, a vortex was visualized in the type 1 phantom that
      rotated counterclockwise at the junction of the caval streams. This apparent
      vortex was not a true vortex; rather, it represented a weakly dissipative
      recirculating zone modulating the flow distribution into the pulmonary arteries.
      The power dissipation and finite-element numeric stimulation confirmed the
      beneficial nature of the apparent vortex and a more energy-saving pattern in the
      type 1 phantom than in the type 2 phantom. CONCLUSION: Total extracardiac
      cavopulmonary connection with left-sided diversion of the inferior vena caval
      conduit anastomosis is characterized by a central vortex that regulates the caval
      flow partitioning and provides a more favorable energy-saving pattern than is
      seen with the total extracardiac cavopulmonary connection with directly opposed
      cavopulmonary anastomoses.

PMID- 12202863
TI  - The role of oxidative stress in the development of pulmonary arteriovenous
      malformations after cavopulmonary anastomosis.
AB  - BACKGROUND: Cavopulmonary anastomosis is used for palliation of cyanotic heart
      disease. Clinically significant pulmonary arteriovenous malformations occur in up
      to 25% of patients after surgical intervention. Cavopulmonary anastomosis creates
      several modifications to pulmonary physiology that may contribute to the
      development of pulmonary arteriovenous malformations, including reduced pulmonary
      blood flow and the exclusion of inferior vena caval effluent. OBJECTIVE: By
      comparing the expression of angiogenic and stress-related proteins after
      cavopulmonary anastomosis and pulmonary artery banding, we sought to determine
      which genes were upregulated independent of reduced pulmonary blood flow.
      METHODS: Lambs aged 35 to 45 days were placed into 1 of 3 groups: cavopulmonary
      anastomosis (n = 6), pulmonary artery banding (n = 6), and sham control (n = 6)
      animals. In our model pulmonary arteriovenous malformations are detectable by
      means of bubble-contrast echocardiography 8 weeks after cavopulmonary
      anastomosis. Lung tissue was harvested for Western blotting at 2 and 5 weeks
      after surgery. RESULTS: Cavopulmonary anastomosis and pulmonary artery banding
      both increased angiogenic gene expression, but only cavopulmonary anastomosis
      induced the expression of endothelial stress-related genes. Vascular endothelial
      growth factor was upregulated 2.5-fold after both cavopulmonary anastomosis (P
      =.002) and pulmonary artery banding (P =.007). Only cavopulmonary anastomosis
      upregulated 2 stress-related genes, HO1 and GLUT1, 2.7-fold (P =.002) and 3.8
      fold (P =.03), respectively. Hypoxia-inducible factor was upregulated 4-fold (P
      =.003) after cavopulmonary anastomosis. Pulmonary artery banding failed to induce
      the increased expression of any of these proteins. CONCLUSIONS: Reduced pulmonary
      blood flow induces a pulmonary angiogenic response but not an endothelial stress
      response. These results suggest that oxidative stress is more relevant to the
      formation of pulmonary arteriovenous malformations than angiogenic signaling
      alone because pulmonary artery banding does not result in pulmonary arteriovenous
      malformations. Oxidative stress of the pulmonary endothelium resulting from
      cavopulmonary anastomosis may predispose the affected vasculature to
      arteriovenous shunting.

PMID- 12202864
TI  - Use of technetium-99m tin colloid for sentinel lymph node identification in non
      small cell lung cancer.
AB  - BACKGROUND: To test the reliability of sentinel lymph node identification in non
      small cell lung cancer, sentinel nodes were localized with a radioactive colloid
      in patients undergoing surgery. METHODS: Forty-six patients with non-small cell
      lung cancer undergoing curative resection with mediastinal lymph node dissection
      were examined. The day before surgery, technetium-99m ((99m)Tc) tin colloid was
      injected into the peritumoral region. At operation, the radioactivity of the
      lymph nodes was counted with a handheld gamma counter before (in vivo) and after
      (ex vivo) dissection. Lymph nodes with an ex vivo radioactive count more than 10
      times the background value were identified as sentinel nodes. The correlation
      between the in vivo and ex vivo results was examined. RESULTS: Lymphoscintigraphy
      revealed that it took longer than 6 hours for sufficient (99m)Tc tin colloid to
      reach the sentinel nodes. Sentinel nodes could be identified in 40 patients
      (87%). Patients whose sentinel nodes could not be identified had a significantly
      lower ratio of forced expiratory volume in 1 second to forced vital capacity than
      did those with identifiable sentinel nodes (P =.03). No false-negative sentinel
      nodes were detected in 14 patients with N1 or N2 disease (0%). In the hilar lymph
      node stations, the lobar lymph nodes were most frequently identified as sentinel
      nodes (as often as 85% of the time). Fourteen patients (35%) had sentinel nodes
      in the mediastinum, the distribution of which depended on the lobe. In vivo and
      ex vivo counting showed 88% concurrence for the identification of sentinel nodes
      in mediastinal lymph node stations. CONCLUSION: The identification of sentinel
      nodes with (99m)Tc tin colloid is a reliable method of establishing the first
      site of nodal metastasis in non- small cell lung cancer. Sentinel nodes could be
      hardly identified in patients with a low ratio of forced expiratory volume in 1
      second to forced vital capacity because of such conditions as chronic obstructive
      pulmonary disease. In vivo identification of sentinel nodes in the mediastinum
      could be useful approach to guide mediastinal lymph node sampling or dissection.

PMID- 12202865
TI  - Correlation between tumor angiogenesis and invasiveness in thymic epithelial
      tumors.
AB  - OBJECTIVE: Because it is difficult to predict the behavior of thymomas on the
      basis of morphology alone, other methods for determining tumor aggressiveness
      must be explored. This study investigated the correlation between angiogenic
      grade and invasiveness in thymic epithelial tumors. METHODS: Immunohistochemical
      studies of 46 surgically resected thymic epithelial tumors (18 noninvasive
      thymomas, 20 invasive thymomas, and 8 thymic carcinomas) were conducted. To
      highlight the microvessels, we used a specific monoclonal antibody against factor
      VIII. Expression of vascular endothelial growth factor and basic fibroblast
      growth factor was determined by using polyclonal antibodies. RESULTS: Mean
      microvessel density readings for noninvasive thymomas, invasive thymomas, and
      thymic carcinomas were 4.6 +/- 3.2, 12.4 +/- 7.5, and 34.4 +/- 16.7,
      respectively. Stages I, II, III, and IV of thymoma had microvessel density
      readings of 4.6 +/- 3.2, 8.5 +/- 4.3, 13.8 +/- 7.7, and 22.0 +/- 6.8,
      respectively. These findings suggest a significant correlation between
      microvessel density and tumor invasiveness. Vascular endothelial growth factor
      expression in noninvasive thymomas, invasive thymomas, and thymic carcinomas was
      present in 1 (5.6%) of 18, 11 (55.0%) of 20, and 5 (62.5%) of 8 patients,
      respectively, thereby indicating a distinct association between vascular
      endothelial growth factor expression and increased microvessel density. Basic
      fibroblast growth factor expression was present in only 8 patients. CONCLUSIONS:
      In patients with thymic epithelial tumors, there appears to be a significant
      correlation between tumor angiogenesis and invasiveness. Furthermore, our data
      suggests that this angiogenesis in thymic epithelial tumors might be, at least in
      part, dependent on vascular endothelial growth factor expression.

PMID- 12202866
TI  - Treatment strategy for chylothorax after pulmonary resection and lymph node
      dissection for lung cancer.
AB  - OBJECTIVE: We reviewed our experience with iatrogenic chylothorax after pulmonary
      resections for lung cancer to evaluate our treatment strategy and to identify
      factors that predict the need for reoperation. METHODS: From July 1992 through
      February 2000, a total of 1110 patients underwent pulmonary resection (at least
      lobectomy) and systematic mediastinal lymph node dissection for lung cancer at
      our division. Twenty-seven patients (2.4%) had postoperative chylothorax develop.
      We initially treated 26 of these patients conservatively with complete oral
      intake cessation and total parenteral nutrition, and these patients constituted
      the subjects in this study. RESULTS: There were 21 men and 5 women with a median
      age of 62 years (range 44 to 80 years). The initial procedures were pneumonectomy
      in 2 cases, bilobectomy in 1 case, and lobectomy in 23 cases. Twenty-one patients
      (81%) had the condition cured with conservative treatment. These patients resumed
      a normal diet at a median of 8 days after chylothorax diagnosis (range 4-35
      days). The remaining 5 patients (19%) underwent reoperation at a median of 14
      days after diagnosis (range 5-35 days). Chest tube drainage of less than 500 mL
      during the first 24 hours after complete oral intake cessation and total
      parenteral nutrition predicted a cure with conservative treatment. CONCLUSION:
      Although most cases of chylothorax after pulmonary resection with systematic
      mediastinal lymph node dissection can be cured with a conservative strategy,
      early surgical intervention may be indicated if chest tube drainage is more than
      500 mL during the first 24 hours after complete oral intake cessation and total
      parenteral nutrition.

PMID- 12202867
TI  - Problems related to TNM staging: patients with stage III non-small cell lung
      cancer.
AB  - OBJECTIVE: Many reports have raised certain problems concerning the current TNM
      classification of lung cancer, namely that there is no sufficient difference in
      prognosis between patients with pathologic stage IIIA and IIIB disease. For
      clarifying this problem, the present study was constructed in light of T3 and T4
      classifications. METHODS: Among 429 patients with non-small cell lung cancer who
      underwent resection, those with stage IIIA (n = 73) and stage IIIB (n = 79)
      disease were enrolled in this study, and their prognostic factors were compared.
      RESULTS: No difference in the survivals between patients with T3 and T4 disease
      was observed, and this seemed to affect the prognoses of patients with stage IIIA
      and IIIB disease. However, when those with T3 and T4 disease were classified into
      different groups on the basis of TNM descriptors, differences in the survivals
      became evident. The T3 bronchial invasion group showed a better prognosis than
      the T3 extrapulmonary invasion group. The T4 tracheal invasion group and T4
      pulmonary metastasis group showed a significantly better prognosis than that in
      the T4 extrapulmonary invasion group and the T4 malignant pleural exudate group.
      The surgical curativity of patients with T3 disease was evaluated as curative
      resection or noncurative resection, and the surgical curativity of T4 was
      evaluated as R0 resection or R1 or R2 resection. The T3 bronchial invasion group
      included more curative resection cases. The T4 tracheal invasion group and T4
      pulmonary metastasis group included more R0 resection cases. Furthermore, when
      patients with T3 to T2 bronchial invasion and patients with T4 tracheal invasion
      and T4 pulmonary metastasis were reclassified as having T3 disease, the survivals
      of the patients reclassified as having T3 and T4 disease, as well as the
      resultant subsets having stage IIIA and IIIB disease, were significantly
      different. CONCLUSION: Tumor status should be reviewed by taking into account the
      surgical curativity.

PMID- 12202868
TI  - The impact of fluorodeoxyglucose F 18 positron-emission tomography on the
      surgical staging of non-small cell lung cancer.
AB  - OBJECTIVES: Staging data on patients with non-small cell lung cancer were
      prospectively collected to evaluate the accuracy and anatomic information
      provided by fluorodeoxyglucose F 18 positron-emission tomography and its impact
      on improving the accuracy of surgical staging. METHODS: A total of 142 patients
      with potentially resectable non-small cell lung cancer were imaged with positron
      emission tomography (neck to pelvis). Positron-emission tomographic scans were
      read prospectively with thoracic computed tomographic comparison. Patients
      without distant metastases at positron-emission tomography underwent staging with
      bronchoscopy and mediastinoscopy, with or without mediastinotomy or thoracoscopy.
      Patients with metastases, pleural implants, or N2 or N3 disease did not undergo
      primary resection. RESULTS: Positron-emission tomography revealed unsuspected
      distant metastases in 24 of 142 patients (16.9%) and unsuspected pleural implants
      in 6 others. Nodal stage was surgically established in 118 cases. Positron
      emission tomography showed that 5 patients had nodal disease not accessible by
      mediastinoscopy. In 35 (24.6%) of these 142 cases, positron-emission tomography
      directed the evaluation away from routine bronchoscopy and mediastinoscopy
      staging that would have resulted in inappropriate treatment selection. Positron
      emission tomography correctly differentiated resectable stages IA through IIIA
      (N1) from stages IIIA (N2) through IV in 88.7% of cases. In identifying N2 or N3
      disease, positron-emission tomography had an accuracy of 90.7%, a sensitivity of
      80.9%, a specificity of 96%, and positive and negative predictive values of 91.9%
      and 90.1%, respectively. Of the 8 cases in which positron-emission tomography
      missed N2 disease, 7 had the disease discovered by mediastinoscopy and 1 had it
      discovered at thoracotomy. CONCLUSIONS: The diagnostic accuracy of positron
      emission tomography-enhanced clinical staging is high. Positron-emission
      tomography has previously been used primarily to screen for lymph node spread and
      distant metastases, but it also provides localizing information that allows
      directed and more sensitive surgical staging and refinement of patient selection
      for curative resection. Positron-emission tomography and surgical staging play
      complementary roles in the journey toward more accurate overall staging.

PMID- 12202869
TI  - A respiratory gas exchange catheter: in vitro and in vivo tests in large animals.
AB  - OBJECTIVES: Acute respiratory failure is associated with a mortality of 40% to
      50%, despite advanced ventilator support and extracorporeal membrane oxygenation.
      A respiratory gas exchange catheter (the Hattler Catheter) has been developed as
      an oxygenator and carbon dioxide removal device for placement in the vena cava
      and right atrium in the treatment of acute respiratory failure to improve
      survival. METHODS: Differing from a previously clinically tested intravenous gas
      exchange device (ie, IVOX), the Hattler Catheter incorporates a small, pulsating
      balloon surrounded by hollow fibers. The pulsating balloon redirects blood toward
      the fibers, enhances red cell contact with the membrane, and significantly
      improves gas exchange so that smaller catheter devices are still efficient on
      insertion and can be inserted through the jugular or femoral vein. Devices were
      tested in mock circulatory loops and in short-term (8 hours) and long-term (4
      days) experiments in calves to study the effect of various sized balloons and the
      anatomic location of the device in the venous system as a function of
      hemodynamics and gas exchange. RESULTS: In vitro performance in water
      demonstrates an oxygen delivery (Vo(2)) of 140 +/- 8.9 mL. min(-1). m(-2) and a
      carbon dioxide removal (Vco(2)) of 240 +/- 6.1 mL. min(-1). m(-2). Acute in vivo
      experiments demonstrate a maximum carbon dioxide consumption of 378 +/- 11.2 mL.
      min(-1). m(-2). Devices positioned in the right atrium had an average carbon
      dioxide exchange of 305 mL. min(-1). m(-2), whereas in the inferior vena cava
      position carbon dioxide exchange was 255 mL. min(-1). m(-2). Devices have been
      tested long term in calves, with gas exchange rates maintained over this time
      interval (carbon dioxide consumption, 265 +/- 35 mL. min(-1). m(-2)). Plasma-free
      hemoglobin levels at the end of 4 days have been 4.8 +/- 3.2 mg/dL. Hemodynamic
      measurements, including a decrease in cardiac outputs and increased mean pressure
      decreases across the device become significant only with the larger balloon (40
      mL) devices (P <.05, 40-mL vs 13-mL devices). Autopsies show no end-organ damage.
      The device linearly increases its carbon dioxide output with progressive
      hypercapnea, predicting its ability to meet tidal volume reduction in the therapy
      of respiratory failure. CONCLUSIONS: Progress has been made toward developing an
      intravenous gas exchange catheter to provide temporary pulmonary support for
      patients in acute respiratory failure.

PMID- 12202870
TI  - The results of total arch graft implantation with open stent-graft placement for
      type A aortic dissection.
AB  - BACKGROUND: One problem that conventional ascending treatment for type A aortic
      dissection has not satisfactorily resolved is chronic enlargement of residual
      dissection in the aortic arch and descending aorta. To address this problem, we
      have developed a new method for type A aortic dissection: total arch graft
      implantation with open-style stent-graft placement. METHODS: From October 1994
      through October 1999, 19 patients with type A aortic dissection (13 acute and 6
      chronic dissections) underwent total arch graft implantation with open-style
      stent-graft placement. After achievement of general anesthesia and hypothermic
      extracorporeal circulation, we replaced the dissected ascending aorta and neck
      vessels with a 4-branched graft and repaired the descending aorta with a stent
      graft to close the entry site completely and to obtain better peripheral
      perfusion. We then examined the acute-phase and chronic-phase results and the
      outcomes of the false lumen and dissected aorta. RESULTS: There were 1 (5.3%)
      hospital death and 2 late deaths. The survivals at 1 and 3 years were 89.5% and
      82.6%, respectively. The following complications occurred in the perioperative
      period: 1 stroke, 2 cases of temporary paraparesis, 2 cases of temporary
      hemodialysis, and 3 cases of mediastinitis. No pulmonary complications were
      observed. Six months postoperatively, the targeted entry sites were completely
      closed in all cases, 80% (8/10) of preoperatively patent false lumina were
      clotted at the level of the end of the stent graft, and 60% (9/15) of the false
      lumina and 40% (6/15) of the dissected aorta had shrunk significantly. Two
      (13.3%) of 15 cases of postoperative dilatation in the dissected aorta were
      observed, and reoperation related to residual dissected aorta was performed in
      only 1 (1/17 [5.9%]) patient during the mean follow-up period of 2.4 +/- 1.6
      years. CONCLUSION: Our preliminary review of the total arch graft implantation
      with a stent graft suggests that this new procedure for type A aortic dissection
      might provide better results in both the acute and the chronic phase, especially
      with regard to the outcome for the false lumen and dissected aorta.

PMID- 12202872
TI  - Bypass grafting with coronary endarterectomy: immediate and long-term results.
AB  - BACKGROUND: Increased morbidity and mortality have been associated with coronary
      artery bypass grafting when an adjunctive coronary endarterectomy is performed.
      In this study we retrospectively reviewed our experience with coronary bypass and
      endarterectomy to evaluate the early and late outcome and to determine the
      independent predictors of early mortality and morbidity of this procedure.
      METHODS: Between May 1989 and December 2000, 107 patients underwent myocardial
      revascularization with coronary endarterectomy to achieve a complete
      revascularization. There were 90 men and 17 women; the mean age was 64 +/- 8.1
      years. Sixty-three (58.9%) patients had a previous myocardial infarction, and 29
      (27.1%) were operated on on an emergency basis. An ejection fraction of less than
      30% was present in 9 (8.4%) patients. The most frequently endarterectomized
      vessel was the left coronary artery (74.8%). Follow-up information was obtained
      from 97 patients (100% of the long-term survivors). RESULTS: There were 5 (4.7%)
      early deaths. The 72-month survival was 91.2% +/- 4.9%. Seventy-seven (83.7%) of
      the survivors were symptom free, and 15 (16.3%) were in Canadian Cardiovascular
      Society class II to III. An improvement of the ejection fraction after the
      operation was shown in the 97 patients who underwent echocardiographic control (P
      =.03) and angiography. The 30.4-month patency rate of the endarteriectomized
      coronary arteries was 72% +/- 11%. CONCLUSION: Coronary endarterectomy is a safe
      and effective procedure for achieving a complete revascularization in patients
      with end-stage coronary disease.

PMID- 12202871
TI  - Hemodynamic performance of an unstented xenograft mitral valve substitute.
AB  - OBJECTIVE: Stentless mitral xenografts offer potential clinical benefits because
      they mimic the normal bileaflet mitral valve. How best to implant them and their
      hemodynamic performance and durability, however, remain unknown. METHODS: A
      stentless porcine mitral xenograft valve (Medtronic physiologic mitral valve) was
      implanted in 7 sheep with papillary muscle sewing tubes attached with transmural
      left ventricular sutures. Radiopaque markers were inserted on the leaflets,
      annular cuff, papillary tips, and left ventricle. After 10 +/- 5 days, the
      animals were studied with biplane videofluoroscopy to determine 3-dimensional
      marker coordinates at baseline and during dobutamine infusion. Transesophageal
      echocardiography assessed mitral regurgitation and valvular gradients. Mitral
      annular area was calculated from the annular markers. Physiologic mitral valve
      leaflet and annular dynamics were compared with 8 native sheep valves. RESULTS:
      Average mitral regurgitation grade at baseline was 1.2 +/- 1.0 (range, 0-4), and
      the mean transvalvular pressure gradients were 3.6 +/- 1.3 and 6.2 +/- 2.2 mm Hg
      during baseline and dobutamine infusion, respectively. Xenograft mitral annular
      area contraction throughout the cardiac cycle was reduced (6% +/- 6% vs 13% +/-
      4% for physiologic mitral valve and control valve, respectively; P =.03).
      Physiologic mitral valve leaflet geometry during closure differed from the native
      valve, with the anterior leaflet being convex to the atrium and with little
      motion of the posterior leaflet. Three animals survived more than 3 months; good
      healing of the annular cuff and papillary muscle tubes was demonstrated.
      CONCLUSION: This stentless xenograft mitral valve substitute had low gradients at
      baseline and during stress conditions early postoperatively, with mild mitral
      regurgitation. Preliminary analysis of healing characteristics appeared favorable
      at 3 months. Additional studies are needed to determine long-term xenograft
      mitral valve performance and resistance to calcification.

PMID- 12202873
TI  - Microflow fields in the hinge region of the CarboMedics bileaflet mechanical
      heart valve design.
AB  - OBJECTIVE: The design of bileaflet mechanical heart valves includes some degree
      of leakage flow on valve closure for the reverse flow to wash the hinge and pivot
      region of the valve. It is believed that this reverse flow helps to prevent areas
      of stasis and inhibit microthrombus formation. However, the magnitude of this
      retrograde flow may also give rise to unacceptable levels of blood element damage
      and lead to platelet activation or hemolysis as a result of the increased flow
      velocities through the hinge region. The purpose of this study was to evaluate
      the hinge flow dynamics of a 23-mm CarboMedics bileaflet mechanical valve (Sulzer
      CarboMedics Inc, Austin, Tex) and then to compare the results with those of the
      St Jude Medical 23-mm Regent (St Jude Medical Inc, Minneapolis, Minn) and
      Medtronic Parallel (Medtronic, Inc, Minneapolis, Minn) valves studied earlier.
      This comparison allows new insight into the microflow fields within the hinge
      region of the CarboMedics bileaflet mechanical valve, which have not been
      previously assessed during its clinical history. METHODS: Two-dimensional laser
      Doppler velocimetry was used to measure the velocity and turbulent shear stress
      fields in the hinge regions. To conduct these measurements, exact dimensional
      models of the bileaflet hinge regions were cast or machined from transparent
      plastic materials. The experiment was conducted in a pulsatile flow loop with
      measurements taken at different levels within the pivot and hinge regions.
      RESULTS: In the 23-mm CarboMedics valve hinge, the phase-averaged forward
      velocity obtained at the flat level and levels of 190 microm and 390 microm above
      flat and 1 mm below flat were 0.54 m/s, 0.77 m/s, 0.3 m/s, and 1.0 m/s,
      respectively. Corresponding values of the peak phase-averaged leakage velocities
      were 3.17 m/s, 2.91 m/s, 2.52 m/s, and 0.5 m/s, respectively. Corresponding
      turbulent shear stresses were 5510 dyne/cm(2), 5640 dyne/cm(2), 4380 dyne/cm(2),
      and 4810 dyne/cm(2), respectively. CONCLUSIONS: The hinge flow dynamics of the
      CarboMedics bileaflet design lie somewhere in between those of the St Jude
      Medical and the Medtronic Parallel valve designs. The fluid dynamics of the
      investigated valve were found to be similar to those of the St Jude Medical
      valves, although with slightly higher leakage velocities and turbulent shear
      stresses. This discrepancy may be a result of the sharper corners associated with
      the hinge design of the CarboMedics valve. It could also be due to the
      incremental enlargement of the internal orifice area of the St Jude Medical
      Regent design.

PMID- 12202874
TI  - Impact of Cox maze procedure on outcome in patients with atrial fibrillation and
      mitral valve disease.
AB  - OBJECTIVE: We sought to determine whether the Cox maze procedure provides
      additional benefit to patients with atrial fibrillation undergoing mitral valve
      operations. METHODS: Between May 1992 and August 2000, we performed 258 Cox maze
      procedures with mitral valve replacement (n = 147) or mitral valve repair (n =
      111). We compared the outcomes of these patients with those of 61 control
      patients with preoperative atrial fibrillation who underwent mitral valve
      replacement alone during the same interval. The three cohorts were similar in
      age, sex, and proportion of patients in preoperative New York Heart Association
      functional class 3 or 4. RESULTS: Although 5-year survivals were similar among
      the groups (94% for mitral valve replacement alone, 95% for mitral valve
      replacement plus maze, and 97% for mitral valve repair plus maze), freedoms from
      atrial fibrillation at 5 years were significantly higher in the mitral valve
      replacement plus maze group (78%) and the mitral valve repair plus maze group
      (81%) than in the mitral valve replacement group (6%, P <.0001). Freedoms from
      stroke at 5 years were 97% for the mitral valve replacement plus maze group, 97%
      for the mitral valve repair plus maze group, and only 79% for mitral valve
      replacement group (P <.0001). Multivariable analysis with Cox hazard model
      revealed that the most significant risk factor for late stroke was the omission
      of the Cox maze procedure (P =.003). CONCLUSIONS: The addition of the Cox maze
      procedure to mitral valve repair and replacement was safe and effective for
      selected patients. Elimination of atrial fibrillation significantly decreased the
      incidence of late stroke.

PMID- 12202875
TI  - Incorporation and integration of implanted myogenic and stem cells into native
      myocardial fibers: anatomic basis for functional improvements.
AB  - BACKGROUND: Myoblasts and stem cells implanted into myocardium can differentiate
      into myocytes and may functionally improve impaired ventricles. For implanted
      cells to actually contribute to the synchronous contractions of the heart,
      however, they must be anatomically integrated with the existing native myocardial
      fibers. METHODS: Isogenic Lewis rats were used as donors and recipients to
      simulate clinical autotransplantation. Either skeletal myoblasts or marrow
      stromal stem cells were isolated from donors, culture expanded, and labeled with
      4',6-diamidino-2-phenylindole (4',6-diamidino-2-phenylindole). Labeled cells were
      then injected into the myocardium of recipients. At intervals specimens were
      obtained, sectioned, and stained with hematoxylin and eosin and
      immunohistochemically against connexin-43 to demonstrate gap junctions
      (intercalated discs). RESULTS: At 1 week the labeled cells were still
      undifferentiated, but early expression of connexin-43 could be detected at
      contact points between the implanted cells and the native myocytes. By 4 to 6
      weeks, labeled, fully differentiated myocytes could be seen to interconnect among
      themselves and with native cardiomyocytes by means of intercalated discs. In
      sections parallel to the myofibers, full integration of new labeled myocytes with
      the native myofiber cells could be observed. Furthermore, the labeled myofibers
      were in parallel with the native, unlabeled fibers. We postulate that such
      supracellular structural integration was enhanced by fiber stretching during
      cardiac contractions, sending signals for cellular reorientation and
      incorporation, in which the cytoskeletal system may play an important role.
      CONCLUSION: We conclude that implanted precursor cells can be integrated into
      native myocardial structure so as to contribute to myocardial function. Direct
      cell-to-cell contact seems to be an important signaling mechanism, which has
      implications for cellular implantation strategies.

PMID- 12202876
TI  - Fibroblast growth factor 2 regulation of mitral valve interstitial cell repair in
      vitro.
AB  - OBJECTIVE: Because elongated mitral valve interstitial cells have features of
      myofibroblasts, it is likely that these cells are essential for the repair of
      injured valve leaflets. We characterized the cellular morphology and pattern of
      repair of these interstitial cells in wounds produced in vitro and tested the
      hypothesis that fibroblast growth factor 2 enhances interstitial cell repair.
      METHODS: Mitral valve interstitial cells were plated onto glass coverslips,
      reached confluence after 1 week, and were wounded by passage of a spatula along
      the center of a monolayer, which created a linear wound with two edges. The
      wounds were observed from 0 to 96 hours by phase-contrast microscopy. Wounds were
      also fixed at 0, 2, and 24 hours and stained for fibroblast growth factor 2 and
      fibroblast growth factor receptor 1 by means of immunofluorescence and laser
      confocal microscopy. RESULTS: Cells in confluent monolayers and in the monolayer
      behind the wound edge formed a multilayered orthogonal pattern of elongated cells
      similar to fibroblasts. Cells along the wound edge migrated into the wound after
      4 hours, and at 24 hours single cells with prominent lamellipodia and tails were
      present within the wound. There was overlapping of cells as well, similar to
      smooth muscle cells. Fibroblast growth factor 2 and fibroblast growth factor
      receptor 1 were present in the cells of the undisturbed confluent monolayer. They
      were upwardly regulated relative to the unwounded monolayer in the cells along
      the wound edge at 2 hours and in the monolayer behind the wound edge at 24 hours.
      In single cells that migrated into the wound, fibroblast growth factor 2 and
      fibroblast growth factor receptor 1 were prominent. Fibroblast growth factor 2
      showed a 6-fold increase in concentration relative to unwounded cultures in
      conditioned medium from wounded cultures at 2 hours after wounding. Addition of a
      neutralizing antibody to fibroblast growth factor 2 significantly delayed wound
      closure at 24 to 96 hours. Addition of exogenous fibroblast growth factor 2 to
      cultures at the time of wounding did not enhance wound repair. CONCLUSION: Mitral
      valve interstitial cells have the ability to repair wounds, and fibroblast growth
      factor 2 is a modulator of these repair processes.

PMID- 12202877
TI  - Improved outcomes in coronary artery bypass grafting with beating-heart
      techniques.
AB  - OBJECTIVE: Although improved outcomes for selected patients by elimination of
      cardiopulmonary bypass have been demonstrated, a benefit for all patients
      undergoing coronary artery bypass grafting by all surgeons has yet to be
      definitively proved. METHODS: We reviewed our experience with beating-heart
      surgery from its inception in January 1995 through December 2000. A total of
      12,540 patients underwent isolated coronary artery bypass grafting, including
      1915 procedures (15%) performed without cardiopulmonary bypass. Groups were
      compared by univariate analysis for preoperative risk factors and postoperative
      complications, and predicted risk was determined by the Society of Thoracic
      Surgeons risk algorithm. RESULTS: There was a gradual increase in the percentage
      of coronary operations performed off pump, from 1.2% in 1995 to 34.1% in 2000.
      Individual surgeon adoption rates ranged from 1% to 96% by 2000. There was a
      decrease in mortality to 3.22%, compared with an overall observed mortality rate
      of 4.0% in the 5 years before beating-heart surgery (P =.0482). There was a
      significant difference in observed mortality between the off-pump and on-pump
      groups (1.9% vs 3.5%, P <.001), despite a higher mean predicted risk among the
      patients in the off-pump group (3.13% vs 2.8%, P <.004). Additionally, decreased
      morbidity in the off-pump group was evidenced by reduced needs for blood products
      (28.45% vs 54.65%, P =.0001), prolonged ventilation (5.83% vs 10.93%, P =.001),
      and reoperation for bleeding (2.41% vs 3.65%, P =.0237), and by shorter hospital
      stay (5.98 vs 7.32 days, P =.001). CONCLUSIONS: Beating-heart surgery can be
      safely assimilated into a cardiac surgical practice, although adoption rates vary
      significantly among individual surgeons. Gradual integration can lead to improved
      outcomes in the total coronary artery bypass surgery population.

PMID- 12202878
TI  - Tumor necrosis factor-alpha production in whole blood after cardiopulmonary
      bypass: downregulation caused by circulating cytokine-inhibitory activities.
AB  - OBJECTIVES: Cardiopulmonary bypass is associated with the release of
      proinflammatory cytokines (tumor necrosis factor alpha, interleukin 1beta,
      interleukin 6, and interleukin 8) and anti-inflammatory cytokines (interleukin 10
      and transforming growth factor beta(1)). On the one hand this cytokine release is
      related to the postoperative systemic inflammatory response syndrome, and on the
      other hand it is related to deterioration of the immune system, for example in
      monocyte or polymorphonuclear neutrophil function, leading to an increased
      susceptibility to infections. To gain further insight into the alterations of
      immune cell reactivity and possible regulatory mechanisms, we studied
      lipopolysaccharide-induced tumor necrosis factor alpha synthesis in whole blood
      from cardiac surgical patients. METHODS: Fifteen patients undergoing elective
      heart surgery with cardiopulmonary bypass were included in the study. Ex vivo
      lipopolysaccharide-induced tumor necrosis factor alpha synthesis was measured in
      a whole blood assay before, during, and after bypass. Corresponding tumor
      necrosis factor alpha messenger RNA levels were determined by semiquantitative
      reverse transcriptase-polymerase chain reaction. In addition, the influence of
      patient serum on whole blood responsiveness and its relationship to anti
      inflammatory cytokines were evaluated in vitro. RESULTS: Tumor necrosis factor
      alpha synthesis was significantly reduced after 30 minutes of cardiopulmonary
      bypass and showed the lowest values at the end of bypass (mean +/- SD 0.109 +/-
      0.105 ng/10(6) white blood cells after 30 minutes of bypass and 0.050 +/- 0.065
      ng/10(6) white blood cells at the end of bypass, vs 0.450 +/- 0.159 ng/10(6)
      white blood cells preoperatively, P <.001). As a further indication of reduced
      cytokine biosynthesis, diminished messenger RNA levels for tumor necrosis factor
      alpha were detected. Serum withdrawn from patients at the end of cardiopulmonary
      bypass reduced tumor necrosis factor alpha synthesis in heterologous blood from
      healthy volunteers highly significantly to 39.93% +/- 23.18% relative to control
      serum (P =.005) and preoperatively drawn serum (P =.024). This effect was dose
      dependent and was not specific for lipopolysaccharide-induced tumor necrosis
      factor alpha synthesis. Anesthesia and heparin administration did not influence
      tumor necrosis factor alpha production significantly. Ex vivo tumor necrosis
      factor alpha synthesis was negatively related to interleukin 10 serum levels,
      positively but weakly related to interleukin 4, and was not related to
      transforming growth factor beta(1) (Spearman correlation coefficients -0.565, P
      <.001, 0.362, P <.001, and -0.062, P =.460, respectively). However, interleukin
      10 levels in patient serum after cardiopulmonary bypass were 300-fold below the
      quantities needed for half-maximal inhibition of tumor necrosis factor alpha
      synthesis in vitro. Moreover, the inhibitory activity could not be removed by
      immune absorption of interleukin 10. CONCLUSIONS: These results suggest that
      during cardiac operations cytokine-inhibitory serum activities are released or
      newly formed. These activities could not be explained by the actions of
      interleukins 4 and 10 or transforming growth factor beta(1). Although their exact
      nature remains undetermined, these substances may contribute to the diminished
      immune cell functions after cardiopulmonary bypass and thus need further
      characterization.

PMID- 12202879
TI  - A rare type of left atrial dissection.

PMID- 12202880
TI  - Lengthy suppression of vascular proliferation by a chymase inhibitor in dog
      grafted veins.

PMID- 12202881
TI  - Extracorporeal membrane oxygenation with nafamostat mesilate as an anticoagulant
      for massive pulmonary hemorrhage after living-donor lobar lung transplantation.

PMID- 12202882
TI  - Sildenafil augments the effect of inhaled nitric oxide for postoperative
      pulmonary hypertensive crises.

PMID- 12202883
TI  - Pneumopericardium after blunt chest trauma: a sign of severe injury?

PMID- 12202884
TI  - Simplified anastomotic technique for end-to-side bronchial reimplantation onto
      the trachea or contralateral main bronchus after complex tracheobronchial
      resections.

PMID- 12202885
TI  - Pulmonary dissemination of tumor cells after extended resection of thyroid
      carcinoma with cardiopulmonary bypass.

PMID- 12202886
TI  - Sympathectomy for truncal hyperhydrosis after traumatic paraplegic injury.

PMID- 12202887
TI  - Middle mediastinal thymoma.

PMID- 12202888
TI  - Megadose of milrinone as an alternative to extracorporeal membrane oxygenation
      for treatment of graft failure early after cardiac transplantation.

PMID- 12202889
TI  - Esophageal injury during radiofrequency ablation for atrial fibrillation:
      inherent safety of radiofrequency bipolar coagulation.

PMID- 12202890
TI  - [Cancer mortality and incidence in Hungary in relation to international data].
AB  - In Hungary mortality caused by malignant tumour diseases is very high. It is the
      second cause of death showing approximately 25% frequency. Statistics on
      disability has revealed that during the past 25 years the number of patients
      become invalid because of cancer has nearly doubled.In comparative international
      statistics cancer mortality and incidence of the Hungarian male population take
      the first and that of the female population the second place. The alarming public
      health problems caused by cancer in Hungary have prompted the authors to identify
      the causes and search for points of outbreak to stop and reverse these
      unfavourable tendencies. When analysing the current state of this country authors
      primarily rely on the studies of the European Cancer Centre, Lyon and those of
      the Hungarian Central Statistical Office (KSH) and National Cancer Registry. By
      years 2000-2001 the National Cancer Registry has become a reliable well
      functioning system. Its activities include the registration of all new cancer
      patients announced in the previous calendar year. Data processing requires
      information such as: year of diagnosis, tumour localisation and extension,
      morphological code and therapeutic interventions. It is a promising sign that the
      first time over the past 25 years cancer mortality decreased in year 2000. The
      unfavourable cancer mortality and incidence status in Hungary might be improved
      by the consistent accomplishment of the project "For a Healthy Nation, A Public
      Health Project for years 2001-2010".

PMID- 12202891
TI  - [Economic evaluation of population-based mass screening for the early detection
      of cancer: a systematic review].
AB  - PURPOSE: The increasing premature mortality due to cancer has made population
      based screening programs for cervical,breast and colorectal cancers inevitable in
      Hungary. However, when confronted with limited resources, the aim is that, within
      the budget constrain, the greatest possible health gain should be "produced".
      METHODS: The authors made a systematic review of the international literature
      concerning the cost-effectiveness of screening programs for the above tumours.
      RESULTS: In case of cervical cancer the Papanicolaou test, in case of breast
      cancer the mammography meet the WHO criteria for population-based mass screening.
      The well-designed organised screening programs are more cost-effective than the
      opportunistic screening. Among sexually active women, according to structure the
      mobile screening buses, according to age group screening of the 30-39 years old
      women seems the most favourable. For breast cancer, screening the 60-70 years old
      population every second year is the reference strategy from a health economic
      perspective. The cost-effectiveness results of either increasing the frequency of
      screening, extending the program for other age groups, or selecting a high-risk
      population are contradictory. In case of colorectal cancer there is no screening
      method, which would meet the WHO criteria. The two-day FOBT seems the most
      favourable, followed by colonoscopy for positive results, in the 55-74 years old
      population every second year. CONCLUSION: In addition to fulfilling requirements
      for a population-based screening method, the cost-effectiveness perspective
      should be taken into account.

PMID- 12202892
TI  - [Spatial accumulation of mortality and morbidity from cancer of the prostate (ICD
      10:C61)].
AB  - The authors examined the spatial accumulation of mortality and morbidity of
      cancer of the prostate of the total as well as age stratified male population of
      Hungary. Using GIS, a descriptive epidemiological study was carried out examining
      the spatial differences of mortality on settlement level with 2000 inhabitants by
      calculating standardized mortality and morbidity ratios. The significance of the
      difference of mortality and morbidity from the national mean was tested by chi
      square probe. On the basis of the results a significant excess in mortality was
      detected in 11 regions of the country. The unfavourable regions cover 11.6% of
      the territory of the country where 25.6% of the male population live. A
      significant excess morbidity can be observed in 8 counties. A significant
      correlation was found between the unfavourable regions of mortality and morbidity
      (r=0.443, p<0.05). The age-specific analysis of morbidity revealed the highest
      excess in morbidity in the age group over 70 years accumulating in 3 counties of
      Transdanubia and in 6 counties of the Great Plain. On the basis of the results of
      mortality and morbidity analysis according to age and areas the unfavourable
      regions can be identified where mortality and morbidity from cancer of the
      prostate accumulates. These studies serve as a basis for intervention strategies.

PMID- 12202893
TI  - [Small area inequalities in breast cancer mortality and screening].
AB  - Despite the unfavourable epidemiological status, the Hungarian breast cancer
      control is a non-appropriately developed system having considerable geographical
      inequalities. The study objective was to describe the small-area pattern of
      breast cancer mortality and of frequency of mammographical examination. The
      influence of socio-economical status on these patterns was also studied. The
      standardised mortality ratios and the standardised relative frequency of
      mammography was determined for settlements, zipcode areas and small regions.
      Their correlations were analysed with education, unemployment ratio, ratio of
      Gypsy and German ethnic minorities, population size, smoking, distance to the
      nearest hospital. The South-Transdanubian Region (STR, consisting of three
      counties, 22 small regions, 444 zipcode areas and 643 settlements) with 1 million
      inhabitants was the study area. All the studied parameters had significant
      spatial variability at all levels of aggregation. Beyond the relatively low
      average mortality risk in the STR, mortality clusters and increasing time trend
      were identified in certain areas. The mortality and the usage of mammography were
      inversely correlated with the indices of deprivation. These factors explain 64.5
      and 17.5% of the whole variability of local mortality risks at the level of
      settlements and small regions. The explanatory role of these factors was
      similarly high for usage of mammography as well (40.2 and 52.6% for small regions
      and zipcode areas). The factors having the strongest influence were the
      population size (in settlement level mortality model), ratio of gypsies (in small
      region level mortality and mammography usage models) and ratio of Germans (in
      mammography usage model for zipcode areas). Inserting the counties' approaches
      for screening organisation into the model, it revealed that the population based
      screening organisation applied in Tolna county has the highest influence being
      4.4 times stronger than the most important socio-economic factors.Altogether,it
      seems that the monitoring of spatial inequalities could improve the performance
      of breast cancer control identifying the populations with special needs, and
      there is a need to explore the pathways by which the socio-economic factors can
      exert their profound influence on the epidemiological status. Moreover, since the
      results clearly demonstrated that it is possible to achieve relatively high
      screening participation rates in Hungarian economical and legislative
      circumstances, the application of this successful method should be encouraged in
      other areas with low performance screening system.

PMID- 12202894
TI  - [Preventive medicine: biomonitoring and chemoprevention].
AB  - The aim of chemoprevention is to delay or prevent the development of pathological
      conditions, or to correct abnormal regulatory mechanisms and in some cases even
      reverse the process. For this intervention to succeed, biomarkers must be found
      that characterize impaired health status in a phase when impairment is still
      reversible. Genotoxicological parameters may function as biomarkers of this kind,
      such as inhibition or delay of mitosis, inhibition of apoptosis, increase in the
      number of chromosomal aberrations, decrease in the capacity of DNA repairing
      enzymes, or parameters characterizing immunological status (eg. decreased NK
      activity). With the help of early signs, impending negative changes or illness
      (which could not be prevented without effective chemoprevention) can be predicted
      in apparently healthy individuals. Thus, the first and most important step in
      chemoprevention is risk characterization. Risk characterization is a complex
      concept, which includes risk analysis, risk assessment and risk management.
      Chemoprevention is a part of the latter process. Biomarkers, which can be studied
      mainly by up-to-date molecular biological methods, are used in discovering risk
      factors and also in the assessment of caused biological effects. Besides avoiding
      risk factors, it is very important to strengthen the protective mechanisms, to
      promote the metabolism of toxic substances, and to repair damage (ward off
      denaturation of macromolecules caused by free oxygen radicals with antioxidants
      for example). Chemopreventive agents are therefore diverse in their targets. Most
      of them have antioxidant properties, such as plant-derived substances, like
      glycosides, flavonoids, various vitamins, carotinoids, and some trace elements
      such as selenium. Another group of chemopreventive agents inhibit cell
      proliferation, or induce programmed cell death (apoptosis). Another group
      influence terminal differentiation, or inhibit angiogenesis. Some chemopreventive
      agents affect the metabolism or detoxification of xenobiotics, or boost the
      functions of the immune system. In many cases these effects are mediated by the
      rate of methylation of DNA molecules.

PMID- 12202895
TI  - [Quality assurance in oncology: experiences of an ISO certification].
AB  - The ISO 9001 quality assurance of the National Institute of Oncology has been
      achieved successfully. We give an account of the brief history and the structure
      of the assurance system of the Institute, the process of setting our goals, and
      also the experience gained from drafting ISO 9001 handbook and flowcharts. Apart
      from the bureaucratic nature of quality assurance, it is a good opportunity for
      us to investigate our everyday work, put it into orderly manner and work more
      reliably. Experience has shown that the introduction of a quality assurance
      system increases the level of patient care, the documentation helps the Institute
      or some of its departments, or even individuals prevent law suits, and serves as
      a sound basis for proposing promotion, salary increases and bonuses, or even
      honors.

PMID- 12202896
TI  - [Selective estrogen receptor modulators (SERMs) in the practice].
AB  - Selective estrogen receptor modulators (SERMs) represent a growing class of
      compounds that act as either estrogen receptor gonists or ntagonists in tissue
      selective manner. SERMs with the appropriate selectivity profile offer the
      opportunity to dissociate the favorable bone and cardio-vascular effects of
      estrogen from its unfavorable stimulatory effects on the breast and uterus. The
      triphenylethylene drug tamoxifen proved to be invaluable to treat and protect
      against breast cancer and bone loss, probably reduces cardiovascular risk, but
      had side effects on uterus similar to natural estrogens. The tamoxifen derivate
      toremifene is also used to treat breast cancer, but has less effect on bone. The
      non-steroidal benzothiophene derivate, raloxifene, is the best SERM available
      thus far. It has the potential to prevent breast cancer (like tamoxifen), but has
      better profile in its actions on bone and cardiovascular system (produces a rapid
      reduction of serum cholesterol, decreases fibrinogen and lipoprotein, improves
      the vascular epithelial function, attenuates vascular intimal thickening, etc.).
      It does not increase the incidence of endometrial cancer. Compounds of this class
      are the first step in developing the perfect hormone replacement and other
      multitargeted therapy. This review summarizes the recent important knowledge
      about SERMs.

PMID- 12202897
TI  - [The rare manifestation of soft tissue metastasis in colorectal cancer].
AB  - The authors report on a rare manifestation of soft tissue metastasis of operated
      colorectal cancer. Interestingly, two years after the resection a etastasis with
      extremely high tumor marker level (CEA, CA 19.9) was detected. Marker elevation
      preceded the manifestation of metastasis by nearly half a year. After the
      metastasectomy the disease progressed. The authors briefly refer to the
      epidemiology of colorectal cancer, the complex therapy and the follow up.

PMID- 12202898
TI  - [Weekly Taxol (Paclitaxel) administration in the second-line treatment of breast
      cancer].
AB  - Based on phase II and III trials Taxol administered in the form of three
      times/week 1 or 3 hr infusion as mono-or combined chemotherapy of breast cancer
      is an effective treatment option. These studies proved that this form of drug
      delivery is effective and well tolerated and the overall response rate is around
      50%. The 1 hr weekly infusion of Taxol is an effective second-line treatment in
      metastatic breast cancer and is better than the 3-weekly infusion since the
      decreased toxicity increases the therapeutic index.

PMID- 12202899
TI  - [Doxorubicin and paclitaxel vs. 5-fluorouracyl, doxorubicin and cyclophosphamid
      in the first line treatment of metastatic breast cancer].
AB  - Combined chemotherapy of breast cancer using antracyclins proved to be superior
      over classical drug combinations. Taxanes are considered even more effective
      agents against breast cancer than the previously used drugs. Based on these
      assumptions, multicentric phase III trial was initiated in Europe to compare the
      AT combination (doxorubicin and paclitaxel) with the classical FAC (5
      fluorouracyl, doxorubicin and cyclophosphamid). AT combination proved to be more
      effective in the treatment of metastatic breast cancer than FAC as far as the
      overall response rate and the complete responses are concerned. Furthermore, the
      time to progression increased in the AT-arm too compared to the FAC-arm. Based on
      these data it is suggested to use AT combination for the first-line treatment of
      metastatic breast cancer.

PMID- 12202900
TI  - [Possibilities and results with Herceptin-Taxol combination in the treatment of
      breast cancer].
AB  - Taxol (paclitaxel) and Herceptin (trastuzumab) are two milestones in the
      treatment of metastatic breast cancer. Accordingly it was feasible to study the
      combination of these two highly active drugs (with different toxicity profiles
      and mechanisms of action) in the treatment of metastatic breast cancer. In
      multicentric phase III trial performed in the US the combination of Herceptin
      with either taxane or anthracyclin was investigated. It was established that the
      combination of Herceptin with Taxol treatment significantly improves the overall
      response rate, increases the time to progression and the overall survival. These
      effects are more pronounced in patients characterized with HER/2 +++
      overexpression. Based on these evidences the Herceptin-Taxol combined treatment
      protocol was introduced in Hungary for the treatment of Stage IV breast cancer
      patients.

PMID- 12202901
TI  - Antitumor vaccines: is it possible to prevent a tumor?
AB  - The main medical use of vaccines is to induce a state of immunity in healthy
      individuals to protect them from deadly or dangerous diseases. In the field of
      cancer immunology, however, vaccines are being used in patients as therapy, often
      with a very poor success rate against advanced disease. This paper reviews recent
      preclinical evidence in favor of the prophylactic use of immunological approaches
      to cancer. Successful attempts at immunological cancer prevention in HER-2/neu
      transgenic mice are described as an example. The specific properties of the HER
      2/neu gene product as a tumor antigen, and the nature of the immune responses
      induced by effective preventive treatments are reviewed. Although the very high
      rate of mammary carcinoma prevention in mice has generated enthusiasm, it should
      not be forgotten that such treatments, when administered to healthy humans at
      risk of cancer, may carry the risk of inducing autoimmunity. These issues can be
      addressed in preclinical studies in appropriate animal models.

PMID- 12202902
TI  - Comparison of the TCR zeta-chain with the FcR gamma-chain in chimeric TCR
      constructs for T cell activation and apoptosis.
AB  - A promising strategy for cancer treatment is adoptive gene therapy/immunotherapy
      by genetically modifying T cells with a chimeric T cell receptor (cTCR). When
      transduced T cells (T-bodies) specifically bind to tumor antigens through cTCR,
      they will become cytotoxic T lymphocytes (CTL) and lyse the tumor cells in a non
      major histocompatibility complex (MHC)-restricted manner. Both the FcR gamma
      chain and the TCR zeta-chain have been used to construct such cTCR, and both have
      shown specific cytolytic functions against tumor cells. However, most researchers
      believe that the zeta-chain generates stronger cytolytic activities against tumor
      than the gamma-chain and therefore would be a better candidate for cTCR
      construction. On the other hand, because of the lack of costimulation signaling
      in such constructs, the T-body might cause activation-induced T cell death (AICD)
      when bound to tumor antigens. Therefore, one can argue that the gamma-chain might
      generate less AICD than the zeta-chain because the gamma-chain has only one
      immunoreceptor tyrosine-based activation motif (ITAM), and the cytolytic
      activities can be therefore recycled. Two cTCR, GAHgamma and GAHzeta, were
      constructed and evaluated for cytokine production, specific cytolytic function
      and AICD in T-bodies after exposure to tumor cells. Using EGP-2-positive LS174T
      colorectal carcinoma cells as targets, there was no substantial difference
      observed between a gamma-chain or zeta-chain as the T-body signaling moiety in
      terms of specific cytolytic functions and induced cytokine production. This paper
      also demonstrates that, in the absence of a costimulation system, tumor antigen
      may not trigger apoptosis of T cells transduced with a cTCR carrying either an
      FcR gamma-chain or a TCR zeta-chain. These observations challenge current ideas
      about the role of ITAM in T cell activation.

PMID- 12202903
TI  - Intratumoral injection of dendritic and irradiated glioma cells induces anti
      tumor effects in a mouse brain tumor model.
AB  - Malignant astrocytoma is the most common primary brain tumor in adults. The
      median survival of patients with malignant astrocytomas (high-grade astrocytomas)
      is about 1-2 years, despite aggressive treatment that includes surgical
      resection, radiotherapy and cytotoxic chemotherapy. Therefore, novel therapeutic
      approaches are needed to prolong survival. We investigated antitumor immunity
      conferred by the intratumoral injection of dendritic (DC) and irradiated glioma
      cells (IR-GC) in a mouse brain tumor model. Intratumorally injected DC migrated
      to the lymph nodes and elicited systemic immunity against autologous glioma
      cells. In a treatment model, intratumoral injection of DC and IR-GC prolonged the
      survival of brain tumor-bearing mice. Efficacy was reduced when studies were
      performed in mice depleted of CD8(+) T cells. Administration of DC or IR-GC alone
      had no effect on survival of brain tumor-bearing mice. CTL activity against
      glioma cells from immunized mice was also stimulated by coadministration of DC
      and IR-GC compared with the controls. These results support the therapeutic
      efficacy of intratumoral injection of DC and IR-GC.

PMID- 12202904
TI  - Chemoimmunotherapy for melanoma with dacarbazine and 2,4-dinitrochlorobenzene
      elicits a specific T cell-dependent immune response.
AB  - An empirically established chemoimmunotherapy for metastatic melanoma combines
      the systemic administration of the chemotherapeutic agent dacarbazine (DTIC) with
      the epifocal application of the contact sensitizer 2,4-dinitrochlorobenzene
      (DNCB) on cutaneous metastases. Although this therapy yields high response rates
      resulting in prolonged survival, the mechanisms involved remain unknown. Here, we
      investigated whether treatment of tumor-bearing mice with DTIC and DNCB resulted
      in a specific immune response against the tumor. Subcutaneous (s.c.) tumors and
      lung metastases were induced in C57BL/6 mice by injecting syngeneic B16-melanoma
      cells s.c. or into the lateral tail vein, respectively. Mice were treated with
      intraperitoneal injections of DTIC followed by epifocal application of DNCB. This
      therapeutic approach significantly reduced the growth of s.c. tumors as well as
      lung metastases. Our data showed that the effector mechanisms involved are
      dependent on T cells. No therapeutic effect was observed in immunodeficient RAG
      1(-/-) mice, or when the contact sensitizer DNCB was replaced by skin irritants
      (croton oil or tributyltin). Splenic lymphocytes obtained from treated mice
      displayed a three-fold higher specific cytolytic activity against B16 cells than
      in tumor-bearing controls. Both CD8(+) and CD4(+) T cells were able to lyse B16
      cells. No changes were observed in natural killer (NK) cell activity. Likewise,
      tumor-infiltrating lymphocytes (TIL) of treated mice showed higher cytolytic
      activity than that of controls. Analysis of cytokine expression in s.c. tumors
      revealed increased mRNA levels of interferon-gamma (IFN-gamma), tumor necrosis
      factor-alpha (TNF-alpha), and interleukin-6 (IL-6) in treated tumors. Together,
      these findings demonstrate the ability of DTIC/DNCB treatment to induce an
      effective T cell-dependent host immune response against a syngeneic tumor.

PMID- 12202905
TI  - Large-scale expansion of CD3(+)CD56(+) lymphocytes capable of lysing autologous
      tumor cells with cytokine-rich supernatants.
AB  - We have developed culture conditions for the efficient expansion of cytotoxic
      effector cells from peripheral blood mononuclear cells (PBMC) by the timed
      addition of cytokine-rich supernatants collected from allogeneic PBMC cultures
      stimulated with anti-CD3 monoclonal antibody (mAb) (allogeneic CD3 supernatants;
      ACD3S). These cytotoxic effectors belonged primarily to CD56(+) natural killer
      (NK) cells, and the cell subset with the greatest cytotoxic activity was an
      otherwise rare population of CD3(+)CD56(+) cells (NKT cells) that expand
      dramatically under these conditions. CD3(+)CD56(+) cytotoxic effectors were
      generated from the PBMC of 16 patients with several types of cancer. The
      CD3(+)CD56(+) cell subset expanded significantly and efficiently lysed NK- as
      well as lymphokine-activated killer (LAK)-sensitive targets. More importantly,
      ACD3S-activated CD3(+)CD56(+) cells were capable of efficiently lysing autologous
      tumor cells including metastatic colorectal, ovarian, breast, lung and pancreatic
      tumor cells as well as melanoma cells. ACD3S-expanded CD3(+)CD56(+) cells
      exhibited increased levels of cytoplasmic interleukin-2 (IL-2), tumor necrosis
      factor-alpha (TNF-alpha), gamma-interferon (IFN-gamma) and perforin.
      CD3(+)CD56(+) cell-mediated cytotoxicity was not restricted by major
      histocompatibility complex (MHC) gene products, since it was not blocked by anti
      MHC class I mAb but was highly inhibited in the presence of CD2- and CD18
      specific mAb. These data suggest that CD3(+)CD56(+) cells expanded under the
      presence of ACD3S may be utilized in clinical protocols for cancer immunotherapy.

PMID- 12202906
TI  - Bi-functional cytokine fusion proteins for gene therapy and antibody-targeted
      treatment of cancer.
AB  - Typically, multiple cytokines act in concert to mediate a desired immunological
      response, and thus more effective therapeutics may be achieved by combining
      several cytokines with potentially synergistic activities. We have developed a
      series of bi-functional cytokine fusion proteins which, when additionally linked
      to an intact antibody (or the Fc portion of an antibody) in a variety of
      configurations, can be specifically targeted. We focus here mainly on the
      synergizing cytokine combination interleukin-2/interleukin-12 (IL-2/IL-12), but
      also demonstrate the utility of this approach with interleukin-4/granulocyte
      macrophage colony-stimulating factor (IL-4/GM-CSF). Cytokine activity was
      retained in constructs where the cytokines were fused in tandem at the carboxyl
      terminus of the Fc or antibody heavy (H) chain, as well as in constructs where
      one cytokine was fused at the carboxyl terminus of the H chain while the second
      cytokine was fused to the amino terminus of either the H or light (L) chain
      variable region. Even in such constructs, antigen binding of the antibody
      cytokine fusion proteins could be maintained. In the context of bi-functional
      fusion proteins, hetero-dimeric IL-12 could be expressed either in a single-chain
      form, or maintained as a heterodimer in which the p40 subunit was fused to IL-2.
      These IL-12/IL-2 bi-functional fusion proteins were shown to induce extremely
      high levels of interferon-gamma (IFN-gamma), similar to the synergy normally seen
      with the combined application of the individual cytokines. In addition, these
      bifunctional molecules were shown to have striking anti-tumor activity as either
      gene therapy or as an antibody cytokine(s) fusion protein, and may provide a
      useful approach to the treatment of cancer.

PMID- 12202907
TI  - Influence of adenoviral vector on expression of angiogenesis regulating factors
      in non-small cell lung cancer cell lines.
AB  - Gene therapy to suppress the neovascularization of solid tumors may prove to be
      an effective strategy in cancer therapy. Recombinant adenovirus (Ad) vectors are
      currently the most widely used vectors for gene transfer. In this study, we
      examined the expression of angiogenesis-regulating factors in tumor cells
      infected with the Ad vector. These cells showed upregulation of basic fibroblast
      growth factor (bFGF) and vascular endothelial growth factor (VEGF) transcription,
      and a higher protein level of intracellular bFGF and increased VEGF secretion. In
      addition, we observed an increase of angiostatin-generating activity in the
      supernatants of infected tumor cells. Supernatants of Ad vector-infected cells
      did not stimulate endothelial cell proliferation, and inhibited their migration.
      These results indicate that infection of tumor cells with the Ad vector results
      in an increase expression of angiogenesis-regulating factors, but does not by
      itself activate angiogenesis.

PMID- 12202908
TI  - Hypoxia and persistent sodium current.
AB  - During prolonged depolarization of excitable cells, some voltage-activated,
      tetrodotoxin-sensitive sodium channels are resistant to inactivation and can
      continue to open for long periods of time, generating a "persistent" sodium
      current ( I(NaP)). The amplitude of I(NaP) is small [generally less than 1% of
      the peak amplitude of the transient sodium current ( I(NaT))], activates at
      potentials close to the resting membrane potential, and is more sensitive to Na
      channel blocking drugs than I(NaT). It is thought that persistent Na channels are
      generated by a change in gating of transient Na channels, possibly because of a
      change in phosphorylation or protein structure, e.g. loss of the inactivation
      gate. Drugs that block Na channels can prevent the increase in [Ca(2+)](i) in
      cardiac cells during hypoxia. Hypoxia increases the amplitude of I(NaP).
      Paradoxically, NO causes a similar increase in I(NaP) and the effects of both can
      be inhibited by reducing agents such as dithiothreitol and reduced glutathione.
      It is proposed that an increased inflow of Na(+) during hypoxia increases
      [Na(+)](i), which in turn reverses the Na/Ca exchanger so that [Ca(2+)](i) rises.
      An increase in I(NaP) and [Ca(2+)](i) could cause arrhythmias and irreversible
      cell damage.

PMID- 12202909
TI  - Model-based analysis of elementary Ca(2+) release events in skinned mammalian
      skeletal muscle fibres.
AB  - Using high temporally and spatially resolved confocal laser scanning microscopy,
      we have recently demonstrated the existence of elementary Ca(2+) release events
      (ECRE) in chemically and mechanically skinned fibres from adult mammalian
      skeletal muscle. Here, we present a first approach to the analysis of mammalian
      ECRE with a spatio-temporal mathematical model of Ca(2+) ion distribution in
      skinned muscle fibre preparations. The differential equations for the main
      processes, including sarcoplasmic reticulum Ca(2+) handling, are solved in a 2-D
      cylindrical geometry by the method of explicit finite differences. By calculating
      the various spatio-temporal ion concentrations as well as the theoretical
      fluorescence signals for confocal microscopy, corrected for the point spread
      function, the model output can be directly correlated with the experimental data.
      Thus, the basic features of mammalian ECRE were successfully reproduced with our
      model. In particular, under our model assumptions a considerable depletion of
      luminal free calcium is predicted even for short spark-like ECRE. For a full
      understanding of the molecular and sub-cellular events responsible for EC
      coupling it is vitally important to combine the experimental and modelling
      approaches to elucidate the contribution of mammalian ECRE to the global Ca(2+)
      release and its alteration under various physiological and also
      pathophysiological conditions.

PMID- 12202910
TI  - Mechanosensory ion channels in charophyte cells: the response to touch and
      salinity stress.
AB  - Mechanosensitive (MS) ion channels are activated by mechanical stress and then
      transduce this information into electrical signals. These channels are involved
      in the growth, development and response to environmental stress in higher plants.
      Detailed analyses of the electrophysiology in higher plants are difficult because
      such plants are composed of complex tissues. The large cells of the charophytes
      facilitate electrophysiological measurements and allow us to study MS ion
      channels at the level of single cells. We draw parallels between the process of
      touch-perception in freshwater Chara, and the turgor-regulating response to
      osmotic shock in salt-tolerant Lamprothamnium. In terms of electrophysiology,
      these responses can be considered in three stages: (1) stimulus perception, (2)
      signal transmission and (3) induction of response. In Chara the first stage is
      due to the receptor potential (RPD), a transient depolarization with a critical
      threshold that triggers action potentials, which are responsible for stages (2)
      and (3). Receptor potentials are generated by MS ion channels. Action potentials
      involve a transient influx of Ca(2+) to the cytoplasm, effluxes of K(+) and Cl(-)
      and a temporary decrease of turgor pressure. Reducing cell turgor increases
      sensitivity to mechanical stimulation. In Lamprothamnium, a hypotonic shock
      produces an extended depolarization that resembles an extended RPD and is
      responsive to osmotic rather than ionic changes. Like the action potential, a
      critical threshold depolarization triggers Ca(2+) influx, opening of Ca(2+)
      sensitive Cl(-) channels and K(+) channels; effluxes that last over an hour and
      result in turgor regulation. These processes show us, in primal form and at the
      level of single cells, how mechanoperception occurs in higher plants. Recent
      progress in research into the role of MS ion channels in the freshwater and salt
      tolerant Characeae is reviewed and the relevance of these findings to plants in
      general is considered.

PMID- 12202911
TI  - From glutathione transferase to pore in a CLIC.
AB  - Many plasma membrane chloride channels have been cloned and characterized in
      great detail. In contrast, very little is known about intracellular chloride
      channels. Members of a novel class of such channels, called the CLICs (chloride
      intracellular channels), have been identified over the last few years. A striking
      feature of the CLIC family of ion channels is that they can exist in a water
      soluble state as well as a membrane-bound state. A major step forward in
      understanding the functioning of these channels has been the recent crystal
      structure determination of one family member, CLIC1. The structure confirms that
      CLICs are members of the glutathione S-transferase superfamily and provides clues
      as to how CLICs can insert into membranes to form chloride channels.

PMID- 12202912
TI  - Modulation of voltage sensitivity by N-terminal cytoplasmic residues in human
      Kv1.2 channels.
AB  - Potassium channels are now among the best understood membrane proteins and most
      salient functions have been mapped onto distinct portions of the protein. The
      detailed mechanism by which movement of the voltage sensor is transduced into
      channel opening is yet to be understood. We have constructed chimaeras from our
      collection of human voltage-gated potassium channels and expressed them in
      Xenopus oocytes. Here we report on a chimaeric construct, 1N/2, generated by
      swapping the N-terminal cytoplasmic residues of hKv1.1 onto the transmembrane
      body of hKv1.2. This chimaera functions as a classic outward rectifier but with a
      25 mV hyperpolarizing shift in the mid-point of channel activation. The
      conductance of oocytes expressing this construct decreases significantly on
      depolarizing beyond +5 mV, unlike full-length hKv1.2. Other parameters such as
      ionic selectivity and charybdotoxin blockage are unaffected in making the
      chimaera. These observations suggest that the introduction of the "foreign" chain
      from hKv1.1 does not cause a large-scale perturbation of channel structure. Loss
      of the N-terminus from hKv1.2 is not responsible for the shift in voltage
      dependence, as a truncation construct, delta75N2, starting at the splice
      junction, has the same voltage-dependence as full-length hKv1.2. Both constructs
      show a maximum in their conductance-voltage curves. This decline in conductance
      on extensive depolarization may arise due to perturbations to the machinery that
      locks channels into their open state on depolarization. Taken together with our
      observations on other N-terminal swapped chimaeras, our data imply that N
      terminal residues can interact with transmembrane regions and perturb the
      machinery mediating voltage-dependent channel gating.

PMID- 12202913
TI  - Linking ion transport, electron flow and oxidative phosphorylation; one aspect of
      the research of Professor Sir Rutherford Ness Robertson, AC, KCMG, DSc, FAA, FRS
      (1913-2001).
AB  - A summary is presented of the work on ion transport of Professor Sir Rutherford
      Ness Robertson.

PMID- 12202914
TI  - A technique for microsecond heating and cooling of a thin (submicron) biological
      sample.
AB  - Temperature excursions of short duration are useful in exploring the effects of
      stress on biological systems. Stress will affect the conformation of biological
      molecules such as proteins, which will lead to an effect on their function. The
      feasibility of generating such temperature excursions is demonstrated by solving
      the heat diffusion equation for an aqueous layer on a silicon wafer. The silicon
      is rapidly heated by a laser pulse and also acts as a heat sink to quench the
      temperature rise. An oxide layer was used to limit the maximum temperature
      attained by the sample. We show that exposures above a 50 degrees C benchmark can
      be confined to times less than 5 micros.

PMID- 12202915
TI  - Solid-state NMR conformational studies of a melittin-inhibitor complex.
AB  - Melittin is a cytolytic peptide whose biological activity is lost upon binding to
      a six-residue peptide, Ac-IVIFDC-NH(2), with which it forms a highly insoluble
      complex. As a result, the structural analysis of the interaction between the two
      peptides is difficult. Solid-state NMR spectroscopy was used to study the
      interaction between melittin and the peptide inhibitor. Location of the binding
      site in the melittin-inhibitor complex was determined using lanthanide ions,
      which quench NMR resonances from molecular sites that are in close proximity to
      the unique ion binding site. Our results indicated that the inhibitor binding
      site in melittin is near Leu13, Leu16 and Ile17, but not near Leu6 or Val8. On
      the basis of these data we propose that the inhibitor binds to melittin in the
      vicinity of Ala15 to Trp19 and prevents insertion of melittin into cell membranes
      by disrupting the helical structure. Supporting evidence for this model was
      produced by determining the distance, using rotational resonance NMR, between the
      [1-(13)C] of Leu13 in melittin and the [3-(13)C] of Phe4 in the inhibitor.

PMID- 12202916
TI  - Biophysics of gating phenomena in voltage-dependent OmpC mutant porin channels
      (R74C and R37C) of Escherichia coli outer membranes.
AB  - The mechanism by which the membrane potential closes and opens voltage-dependent
      beta-barrel membrane channels is not fully understood. OmpC porins form trimeric
      water-filled channels when incorporated into artificial bilayers, each monomer
      having a conductance of approximately 510 pS in 1 M KCl. These channels are
      relatively insensitive to membrane potential difference (pd) and close only when
      the pd exceeds +/-250 mV. Another well-known trimer, OmpF, has a monomer
      conductance of approximately 780 pS in 1 M NaCl, is more sensitive to pd, and can
      be closed reversibly when a pd of more than +/-150 mV is applied to the channel
      containing membranes. With the aid of the 3D atomic structure of these channels
      determined by X-ray crystallography, and using site-directed mutagenesis,
      specific amino acids can be substituted in desired locations in the channel
      lumen. In this study we have used mutants 37C and 74C and attached fluorescence
      probes to them to monitor polarity changes in the channel lumen during gating.
      From the observed changes in polarity, we conclude that conformational changes
      occur in the channel which interrupt the electrolyte conducting pathway.

PMID- 12202917
TI  - Functional and spectroscopic studies of a familial hypertrophic cardiomyopathy
      mutation in Motif X of cardiac myosin binding protein-C.
AB  - Familial hypertrophic cardiomyopathy is an autosomal dominant genetic disorder
      caused by mutations in cardiac sarcomeric proteins. One such mutation is a six
      amino acid duplication of residues 1248-1253 in the C-terminal immunoglobulin
      domain of cardiac myosin binding protein-C, referred to as Motif X. Motif X binds
      the myosin rod and titin. Here we investigate the structural and functional
      alteration in the mutant Motif X protein to understand how sarcomeric dysfunction
      may occur. The cDNA encoding Motif X was cloned, mutated and expressed as wild
      type and mutant proteins in a bacterial expression system. Circular dichroism
      spectroscopy confirmed that the normal and mutant Motif X exhibited a high beta
      content, as predicted for immunoglobulin domains. Thermal denaturation curves
      showed that Motif X unfolded with at least two structural transitions, with the
      first transition occurring at 63 degrees C in the wild-type but at 40 degrees C
      in the mutant, consistent with the mutant being structurally less stable.
      Sedimentation binding studies with synthetic myosin filaments revealed no
      significant difference in binding to myosin between the wild-type and the mutant
      Motif X. Molecular modeling of this duplication mutation onto an homologous IgI
      structure (telokin) revealed that the duplicated residues lie within the F strand
      of the immunoglobulin fold, on a surface of Motif X distant from residues
      previously implicated in myosin binding. Taken together, these data suggest that
      the Motif X mutation may interfere with other, as yet unidentified, functional
      interactions.

PMID- 12202918
TI  - Prion channel proteins and their role in vacuolation and neurodegenerative
      diseases.
AB  - The prion encephalopathies, which are characterized by neuropathological changes
      that include vacuolation, astrocytosis, the development of amyloid plaques and
      neuronal loss, are associated with the conversion of a normal cellular isoform of
      prion protein (PrP(c)) to an abnormal pathologic scrapie isoform (PrP(Sc)). The
      use of PrP[106-126] and its isoforms in studies of channels in lipid bilayers has
      revealed that it forms heterogeneous channels reflecting modifications in the
      peptide's structure and differences in the properties of the formed oligomeric
      aggregates and their intermediates. We propose that the accumulation of
      pathological isoforms of prion are linked to membrane abnormalities and
      vacuolation in prion diseases. The interlinked changes in membrane fluidity and
      endogenous channels induced by prion isoforms can occur independently and
      concurrently with channel formation, i.e. they are not mutually exclusive. We
      suggest that vacuolation is a cellular response triggered in order to immobilize
      pathological prion isoforms having the ability to form channels that compromise
      cellular membranes. This mechanism is similar to that of other channel-forming
      proteins that induce vacuolation, e.g. the well-established VacA of Helicobacter
      pylori, Vero cells and aerolysin, as well as melittin-induced micellization and
      membrane fusion. We conclude that channel formation is part of the molecular
      mechanisms responsible for the vacuolation associated with prion diseases. The
      initial vacuolation could be an adaptive cellular response to compartmentalize
      the increase in pathogenic prion isoforms, while an excessive accumulation of
      pathologic prion isoforms in later stages represents the inability of the cell to
      continue to compartmentalize these misfolded proteins in vacuoles.

PMID- 12202919
TI  - Estrogenic activity of musk fragrances detected by the E-screen assay using human
      mcf-7 cells.
AB  - The widespread use of synthetic musk fragrances and the resultant presence of
      these substances and their metabolites in the aquatic environment (as well as
      their accumulation in human adipose tissue) raises the question of whether musk
      fragrances display endocrine and in particular estrogenic activity. A variety of
      musk fragrances were tested using the E-screen assay. A statistically significant
      increase in proliferation rate of human MCF-7 breast cancer cells was detected
      for two nitro musks (musk xylene, musk ketone), a major metabolite of musk xylene
      ( p-amino-musk xylene), and the polycyclic musk fragrance AHTN. This indicates
      that these substances do, in fact, demonstrate estrogenic activity. Coincubation
      with the antiestrogen tamoxifen showed that the increase in proliferation rate by
      the musk fragrances is estrogen receptor-mediated. It must be noted, however,
      that the effective estrogenic strength and estrogenic potency were low compared
      to 17 b-estradiol. The naturally occurring fragrance muscone from the group of
      macrocyclic musk fragrances, a group of substances that have not yet been well
      characterized in respect to their toxicological properties, has also been shown
      to be weakly estrogenically active in vitro. E-screen analysis showed that the
      nitro musk metabolites o-amino musk xylene and 2-amino-MK, the macrocyclic musk
      fragrances ethylene brassylate, ethylene dodecandioate, and cyclopentadecanolide,
      are not estrogenically active.

PMID- 12202920
TI  - Bisphenol a degradation by bacteria isolated from river water.
AB  - Recently, there is increasing interest in the microbial degradation of endocrine
      disruptors. This study was conducted to show the isolation and property of
      bacteria having bisphenol A (BPA) biodegradability in river water and to identify
      the difference of BPA degradation under aerobic and anaerobic conditions. Three
      river water samples spiked with BPA (1 mg/L) were rapidly degraded under aerobic
      conditions. The half-life for BPA degradation ranged from 2 to 3 days, and BPA
      was below detection limit (less than 0.005 mg/L) on the 10th day. But a decrease
      of BPA under anaerobic conditions was hardly identified at 30 degrees C for 10
      days (less than 10%). Also, most bacteria (10 out of 11) isolated from three
      river waters had BPA biodegradability, but there were differences in removal
      rates of BPA (18% to 91%). Moreover, two strains that had high BPA
      biodegradability (about 90%) were identified as a Pseudomonas sp. and a
      Pseudomonas putida strain.

PMID- 12202921
TI  - Nitrates/nitrites alter human lymphocyte proliferation and cytokine production.
AB  - Nitrate from drinking water is converted in the body to nitrite by bacteria in
      the gut. This project examined effects of nitrate/nitrite on immune functions,
      i.e., human lymphocyte proliferation and cytokine production. Nitrate had no
      effect on lymphocyte growth, but nitrite decreased proliferation. Neither
      inhibited fibroblast growth. In 1/3 to 2/3 of the subjects tested, sodium nitrate
      or nitrite decreased production of Th1 cytokines (interleukin-2, interferon
      gamma, and tumor necrosis factor-beta). Nitrate and nitrite either increased or
      had no effect on the production of the Th2 cytokine interleukin-10. A Th1 immune
      response is associated with resistance to a variety of infectious diseases; a Th2
      response is associated with disease susceptibility. Because nitrate/nitrite
      shifted the balance from a Th1 to a Th2 response in some individuals, exposure to
      these compounds may decrease these persons' responsiveness to infectious
      diseases. The levels of nitrate used in this study are relevant to human health
      because they are present in the liquid portion (nonbreastfed) of some 2-month-old
      infants' diets in rural Romania.

PMID- 12202922
TI  - Horizontal and vertical distribution of butyltin compounds in sediments from
      shipyards in Korea.
AB  - Butyltin compounds were quantitatively determined in surface sediment and
      sediment core samples near shipyards in the south coast of Korea, which is one of
      the major ship building industries in the world. Tributyltin (TBT) concentrations
      reached up to 46100 ng Sn/g on a dry-weight basis at the front of the shipyard.
      Horizontal distribution of butyltin compounds was closely related to dry-docking
      activities. Butyltin concentrations were relatively low where remote from the
      sources. The vertical distribution of TBT in sediment cores showed active use of
      TBT in Korean peninsula for the past decades. The increase of TBT concentrations
      in sediment core according to estimated sediment age demonstrated a positive
      correlation with the increase of gross tonnage of ships built in the shipyard for
      20 years. High TBT residue levels in sediment core samples raise concerns over
      persistence of the compound in the marine environment.

PMID- 12202923
TI  - Cytogenetic damage in shallot ( Allium cepa) root meristems induced by oil
      industry "high-density brines".
AB  - Saturated water solutions of calcium chloride, calcium bromide (densities 1.30 kg
      x dm(-3) and 1.61 kg x dm(-3), respectively) and their 1:1 mixture have been
      commonly used as oil industry "high-density brines." In our experiment they were
      added to tap water in amounts appropriate to achieve concentrations of 0.025,
      0.05, 0.075, and 0.1 mol x dm(-3) to study their cytotoxic effect on the root tip
      cells of shallot ( Allium cepa L. var. ascalonicum). All tested solutions in
      concentrations of 0.075 and 0.1 mol x dm(-3) caused significant inhibition of
      shallot root growth. CaBr (2) showed this effect in concentration 0.05 mol x dm(
      3). The investigated solutions in all concentrations applied decreased mitotic
      activity in root tip cells. The most of mitotic abnormalities were the
      consequence of spindle failure and chromosome stickiness. Furthermore, the cell
      microtubules were investigated by indirect immunofluorescence to confirm that
      most abnormalities observed were the consequence of spindle failure. The present
      study, as well as previously done Lemna tests and Chlorella tests showed that
      investigated samples have certain effects on plants, so constant control of their
      presence in the environment is needed.

PMID- 12202924
TI  - Comparision of atrazine and metolachlor affinity for bermudagrass ( Cynodon
      dactylon L.) and two soils.
AB  - Given that bermudagrass is being used as one of the grasses of choice in grass
      filter strip plantings as an acceptable grass to reduce off-target losses of
      herbicides, laboratory experiments were conducted to determine and compare the
      relative affinity of bermudagrass, a Weswood soil, and a Houston Black soil for
      atrazine (6-chloro- N-ethyl- N-isopropyl-1,3,5-triazine-2,4-diamine) and
      metolachlor (2-chloro- N-(2-ethyl-6-methylphenyl)- N-(2-methoxy-1-methyethyl)
      acetamide). Experiments were also conducted to determine if the presence of one
      herbicide affects the relative affinity of the other compound to these sorbents.
      The experiments were carried out using radiolabeled atrazine and metolachlor.
      Results were reported in disintegrations min(-1) (dpms) and converted to K(d) to
      determine and compare relative affinity. Both K(d) values for relative affinity
      of atrazine (86.2) and metolachlor (131.5) to bermudagrass were significantly
      greater than those of the two soils, Weswood (atrazine, 20.0 and metolachlor,
      28.4) and Houston Black (atrazine, 35.8 and metolachlor, 33.5). The two compounds
      were also mixed together to mimic the common practice of applying atrazine and
      metolachlor simultaneously as a tank mix. Relative affinity of atrazine to any of
      the sorbents was not affected by the presence of metolachlor. Similarly, when
      comparing the affinity of metolachlor alone to that of metolachlor with atrazine
      present in the solution, no significant differences were observed for
      bermudagrass or the Weswood soil. However, on the Houston Black soil, the
      presence of atrazine significantly increased the soil's affinity for metolachlor.

PMID- 12202925
TI  - Control of brackish water fouling mussel, Mytilopsis leucophaeata (Conrad), with
      sodium hypochlorite.
AB  - Though the Conrad's false mussel, Mytilopsis leucophaeata, is an important
      fouling animal in industrial cooling water systems, there are no published
      reports on the tolerance of this species to chlorination. A series of experiments
      was conducted to determine the effects of mussel size (2-20 mm shell length),
      season (breeding versus nonbreeding), nutritional status (fed versus starved) and
      acclimation temperature (5-30 degrees C) on the mortality pattern of M.
      leucophaeata under continuous chlorination (0.25-5 mg/L). The effect of mussel
      size on M. leucophaeata mortality in the presence of chlorine was significant,
      with 10 mm size group mussels showing greater resistance. At 0.25 mg/L residual
      chlorine, 2 mm size group mussels took 89 days to reach 100% mortality, whereas
      10 mm size group mussels took 109 days. M. leucophaeata collected during
      nonbreeding season (December-April) was more tolerant to chlorine than those
      collected during breeding season (June-October). Nutritional status of the mussel
      had no significant influence on the chlorine tolerance of the mussel: fed and
      starved mussels succumbed to chlorine at equal rates. The effect of acclimation
      temperature on M. leucophaeata mortality in the presence of chlorine was
      significant. At 0.5 mg/L residual chlorine, mussels acclimated at 5 degrees C
      required 99 days to reach 95% mortality, whereas mussels acclimated at 30 degrees
      C required 47 days. A comparison of present data with previous reports suggests
      that resistance of M. leucophaeata to chlorination is higher than other mussel
      species causing fouling problems in The Netherlands ( Mytilus edulis and
      Dreissena polymorpha).

PMID- 12202926
TI  - Metal concentrations in zebra mussels and sediments from embayments and riverine
      environments of eastern Lake Erie, southern Lake Ontario, and the Niagara River.
AB  - Concentrations of 14 metals were studied in the soft tissues of zebra mussels (
      Dreissena polymorpha) and sediments from 16 Great Lakes embayments and riverine
      environments. Samples were collected in 1993 and 1994 during the early and late
      autumn period when the body mass of mussels is least affected by reproductive
      activities. There was a significant difference in geometric mean concentrations
      of all metals except Cu in mussels sampled from different sites, and there was a
      significant difference in the geometric mean concentrations of all metals but Cd,
      Mn, and Zn between years. The higher metal concentrations in mussels from this
      study were generally similar to those in mussels from contaminated European and
      U.S. locations, and those with lower concentrations were similar to those from
      uncontaminated European and U.S. locations. Geometric mean sediment
      concentrations of all metals differed significantly among sites. Sediment
      concentrations of metals from some sites were above EPA guidelines for moderately
      polluted harbor sediments. Sites where zebra mussels had higher concentrations of
      Al, Cr, and V tended to be the same sites as those where sediment concentrations
      of these metals were also higher. However, there was not a significant
      statistical relationship between concentrations of metals in zebra mussels and
      sediments, except for Mg.

PMID- 12202927
TI  - Mercury concentrations in fish from Lake Mead, USA, related to fish size,
      condition, trophic level, location, and consumption risk.
AB  - Total mercury (Hg) concentrations were determined in the skeletal muscle of 339
      fish collected during the fall of 1998 and spring of 1999 from Lake Mead, USA,
      the nation's largest human-made reservoir. Five species of fish representing a
      range of trophic levels and the lake's principal game fishes were studied. Hg
      generally increased with trophic level and fish size. Median Hg concentrations
      (ng/g wet mass) were 277 in striped bass, 168 in channel catfish, 160 in
      largemouth bass, 75 in bluegill, and 8 in blue tilapia. Overall, fish from Las
      Vegas Bay and Boulder Basin had the lowest Hg concentrations, possibly a result
      of biodilution in this biologically productive area. In general, fish-mercury
      advisories might include a warning about consuming fillet from emaciated fish,
      based on the finding that Hg concentrations in 59 striped bass (captured during a
      scarce-food season) correlated inversely ( r = -0.89, p < 0.001) with a fish
      nutritional-status factor. This is consistent with starvation-concentration,
      whereby Hg in fish muscle is lost at a slower rate than the muscle mass. The
      median concentration found for 139 striped bass corresponds to a recommended risk
      based consumption limit of three 8-oz. (227-g) meals per month for a 70-kg adult.
      Finally, this paper serves as a useful archive for future research and long-term
      studies of Hg in Lake Mead fish.

PMID- 12202928
TI  - Northern bobwhite and lead shot deposition in an upland habitat.
AB  - We estimated total lead shotshell pellets expended, resultant pellet availability
      near soil surface, and the frequency of pellet ingestion by northern bobwhites (
      Colinus virginianus) attributable to nearly a quarter century of bobwhite hunting
      on a 202-ha upland habitat at Tall Timbers Research Station, Leon County,
      Florida. A total of 7776 shots were fired, resulting in the expenditure of
      approximately 4.5 million pellets (approximately 22519/ha). Sixteen of 235 (6.8%)
      soil samples collected in 1989 and 1992 contained one or two pellets. Soil
      samples indicated that approximately 7800 pellets/ha (about 35% of the projected
      24-year deposition) were within 2.54 cm of the soil surface. Pellet ingestion by
      bobwhites was evaluated by examining 241 gizzards collected from 1989-92. Three
      bobwhites (1.3%) had ingested pellets ( x = 1.3 pellets). No instances of
      suspected lead poisoning were noted in bobwhites over the 24-year period. Sport
      hunting of wild bobwhite populations on upland habitats appears to produce a low
      potential for lead poisoning compared to lead deposition in association with
      waterfowl and dove hunting.

PMID- 12202929
TI  - Inter- and intraclutch variability in heavy metals in feathers of great tit
      nestlings ( Parus major) along a pollution gradient.
AB  - Heavy metal (silver, arsenic, cadmium, copper, mercury, lead, and zinc)
      concentrations were analyzed in feathers of nestling great tits ( Parus major)
      collected along a pollution gradient. Differences in metal concentrations along
      the gradient and inter- and intraclutch variability were investigated. In the
      immediate vicinity of the pollution source, feathers of nestling great tits
      contained significantly higher concentrations of silver, arsenic, mercury, and
      lead than at the sites further along the gradient. The concentrations of copper
      and zinc, two essential metals, were significantly lower at the second most
      polluted site. There was no significant difference in cadmium concentrations
      among sites. Most metals, except cadmium, were significantly positively
      correlated with each other. There was a significant amount of interclutch
      variability in feather metal concentrations, and they differed significantly
      among sites. The amount of inter- and intraclutch variability did not differ
      significantly, although intraclutch variability of most metals was markedly high.
      Our study indicates that feathers of great tit nestlings could be used as
      bioindicators of metal pollution, but attention should be paid in designing
      representative sampling procedures.

PMID- 12202930
TI  - Effects of Phos-Chek G75-F and Silv-Ex on developing northern bobwhite quail
      (Colinus virginianus).
AB  - Eggs of nesting birds situated in peripheral areas serving as fire breaks are at
      risk of being sprayed with fire control chemicals. Acute toxicity tests were
      conducted by immersing northern bobwhite quail eggs for 10 s in different water
      based concentrations of Silv-Ex(R) (SE), a foam-suppressant chemical, and Phos
      Chek(R) G75-F (PC), a fire retardant chemical, on day 4 or day 11 of incubation.
      An attempt was made to relate the treatment concentrations to the actual field
      application levels. Mortality appeared higher in most groups exposed on day 11
      than on day 4, suggesting that on day 11 the extensive chorioallantoic vascular
      network permitted greater uptake of chemical. Only 24-60% of the embryos survived
      to hatch at exposure concentrations of 202, 269, and 454 g/L PC when treated on
      incubation day 11. At higher concentrations including 681956, and 1211 g/L PC,
      the compound did not completely dissolve in water and clumped on eggshells,
      resulting in greater hatching success. Exposures to SE at 100 g/L on incubation
      day 11 did not significantly affect hatching success of embryos but did
      significantly reduce the percent hematocrit in blood compared with controls.
      Incubation day 11 exposure to 202 and 1211 g/L PC led to a significant increase
      in plasma aspartate aminotransferase, and day 4 exposure to 1211 g/L PC resulted
      in a significant increase in alanine aminotransferase. In addition to elevated
      liver enzymes, these treatments resulted in a decrease in the number of
      hepatocyte profiles (1211 g/L PC at day 4 and day 11) and an increase in
      hepatocyte size (202 and 1211 g/L PC at day 11) in hatchlings. A combination of
      SE and PC was synergistic (202 g/L PC and 50 g/L SE) at day 11 of incubation with
      respect to decreased hatching success and reduced bone lengths. However, lower
      concentrations of SE (10 g/L or 30 g/L) combined with 202 g/L of PC appeared
      antagonistic. This may be due to SE, as a surfactant, altering the ability of PC
      to penetrate the egg. Our results show fewer adverse effects following exposure
      to SE than to PC; therefore application of SE may be less harmful to breeding
      bird populations.

PMID- 12202931
TI  - Thyroid hormone suppression and cell-mediated immunomodulation in American
      kestrels (Falco sparverius) exposed to PCBs.
AB  - Exposure to environmental contaminants can induce physiological changes in
      animals through various mechanisms. One manifestation of subclinical toxicity
      from polychlorinated biphenyl (PCB) exposure is the disruption of normal immune
      function described in numerous species, including American kestrels (Falco
      sparverius). In 1998, 152 mature male and female kestrels were fed either a
      mixture of Aroclor 1248:1254:1260 (approximately 7 mg/kg kestrel/day) through
      their food items, or control diets. Offspring produced by 50 breeding pairs
      (thus, half received in ovo PCB exposure only) were also studied. Total and
      differential white blood cell counts, the phytohemagglutinin (PHA) skin response,
      as well as thyroid hormone levels were tested in vivo in nonbreeding adults (1998
      only) and nestlings (1998 and 1999). In 1999, nestlings came from three parental
      groups; adults exposed in 1998, birds produced by PCB-exposed parents, and
      unexposed birds. In 1998, directly exposed males but not females had increased
      total white blood cell counts driven by lymphocytosis, plus a decreased
      heterophil-to-lymphocyte ratio relative to controls. PCB-exposed birds had a
      significantly greater response to PHA than did controls, with sex as a
      significant factor and plasma triiodothyonine (T(3)) as a significant covariate.
      Levels of T(3) were significantly depressed in PCB-exposed birds of both sexes.
      The 1999 nestlings (F1 generation with respect to PCB exposure) did not show any
      effect of parental treatment group on the PHA skin response, yet T(3) remained as
      a significant covariate. Immunological effects are discussed in light of the
      antibody-mediated immunotoxicity found in the same birds and reported previously.

PMID- 12202932
TI  - Lack of a distinct gradient in biomarker responses in small mammals collected at
      different distances from a highway.
AB  - This study describes biomarker effects in small mammals exposed to traffic
      emissions. Animals were collected at 10-50 m (site 1), 150-200 m (site 2), and 5
      km (site 3) from a very busy highway (A2). To distinguish between routes of
      exposure, strictly carnivorous common shrews ( Sorex araneus) and predominantly
      herbivorous bank voles ( Clethrionomys glareolus) were collected. As a measure of
      exposure to polycyclic aromatic hydrocarbons (PAHs), aromatic DNA adduct levels
      were determined by (32)P-postlabeling techniques in tissue from heart, lung, and
      liver. Lead (Pb), cadmium (Cd), and copper (Cu) levels were analyzed in kidney as
      a measure of exposure to heavy metals. EROD and PROD activity and retinoid levels
      were determined in liver as effect biomarkers for exposure to PAHs and
      polyhalogenated aromatic hydrocarbons (PHAHs). Relatively high Cd levels in S.
      araneus and in particular elevated DNA adduct levels in C. glareolus indicated
      that small mammals at site 3 were exposed to more compounds than at sites 1 and 2
      (3 > or = 1 > 2). The latter effect is probably due to an incidental and actual
      input of airborne pollutants that is deposited on plant surfaces. By consumption
      of above-ground vegetation, voles are chronically exposed to this pollution.
      Relatively high background input of PAHs probably hinders that the traffic
      related gradient of airborne PAH concentrations found in an earlier study is
      reflected in DNA adduct levels in small mammals in the present study. Moreover,
      historical biomarkers for exposure to traffic emissions, such as increased kidney
      Pb levels, increased hepatic EROD activity, and disturbed hepatic vitamin A
      homeostasis are no longer applicable to indicate differences in exposure. This is
      a result of the ban on addition of Pb and chlorinated scavengers to gasoline and
      of cleaner combustion techniques, which were enforced by law over the past
      decade. Finally, it is advisable to use only juvenile small mammals for in situ
      monitoring of diffuse pollution because DNA adduct levels increased with age.

PMID- 12202933
TI  - Raccoon (Procyon lotor) as a bioindicator of mercury contamination at the U.S.
      Department of Energy's Savannah River Site.
AB  - Raccoons (n = 95) were collected from the U.S. Department of Energy's Savannah
      River Site (SRS) and from public hunting areas. Raccoons were collected near a
      stream drainage system (Steel Creek delta) and a former reactor-cooling reservoir
      (pond B) that received inputs of mercury-contaminated Savannah River water.
      Mercury concentrations were determined for hair, liver, kidney, muscle, and
      spleen tissues. Samples were analyzed using inductively coupled plasma mass
      spectroscopy (ICP-MS) and cold vapor atomic absorption spectroscopy (CVAAS).
      Raccoons were also collected from a natural stream floodplain system (Upper Three
      Runs/Tinker Creek) located upstream of Hg use and storage areas and near coal ash
      basins. These samples were compared to samples collected from off-site hunting
      areas near the SRS. Hg concentrations between internal tissues were significantly
      correlated. Hair did not correlate well with internal tissue and was a weak
      indicator of raccoon exposure to Hg. Nonetheless, raccoons are potentially good
      indicators of Hg contamination because tissue concentrations were higher in
      raccoons from areas with known Hg input than in those from reference areas, and
      muscle biopsies can be used as biomarkers for contaminant exposure. Muscle Hg
      concentrations ranged from 0-0.14 ppm from nearby hunting grounds, indicating
      that people hunting in designated areas near the SRS are at negligible risk for
      Hg consumption from raccoon meat. Several raccoons collected from the SRS had
      muscle Hg concentrations at or near the FDA action level for seizing commercial
      fish due to mercury contamination of 1.0 ppm. Though Hg action levels for wild
      game have not been proposed, it is clear that some SRS raccoons had Hg levels
      that warrant concern if these areas would be open to public hunting. Last, 64
      raccoons from this study had Hg concentrations that were considered elevated by
      the U.S. FWS standard (> 1.1 ppm) of ecosystem health for one or two tissues
      (hair, liver, or kidney), and 17 had high concentrations for most or all tissues.

PMID- 12202934
TI  - Organochlorine hydrocarbons in human breast milk collected in Hong Kong and
      Guangzhou.
AB  - In southern China, the awareness of persistent organic pollutant contamination
      has been increasing as a considerable number of past studies in Hong Kong had
      reported their trail in the coastal sediments, green-lipped mussels, muscle and
      viscera of pond fish, and foodstuffs. Hence there is an urgent need to assess
      their existence, contamination profiles, and potential impact on the public. In
      the present study, a survey was conducted to examine p,p'-DDT, p,p'-DDE, beta
      HCH, and PCB concentrations in human breast milk, one of the most reliable
      bioaccumulation indicators. Milk samples (115 from Hong Kong and 54 from
      Guangzhou), in the lactation period from 3-5 weeks were analyzed. The results
      demonstrated that the mean levels of p,p'-DDT (Hong Kong: 0.39; Guangzhou: 0.70
      microg/g of fat), p,p'-DDE (2.48; 2.85), and beta-HCH (0.95; 1.11) were 2-15-fold
      higher when compared with studies conducted elsewhere ( i.e., United Kingdom,
      Germany, Sweden, Spain, and Canada), and in contrast the concentration of PCBs
      (0.035; 0.031) was about 10 times lower. When compared to a similar study
      conducted 10 years ago in Hong Kong ( p,p'-DDT 2.17 microg/g of fat, p,p'-DDE
      11.67, beta-HCH 15.96, and PCB 0.64), a considerable reduction in the levels of
      their contaminations was observed. The drastic reduction in body burdens in 10
      years' time is presumably the result of effective regulatory actions. It is worth
      noting that body burden correlated positively with maternal age (total DDT, r =
      0.93; beta-HCH, r = 0.91; PCBs, r = 0.77) and with historical record of seafood
      consumption (total DDT, r = 0.89; beta-HCH, r = 0.98; PCBs, r = 0.91) (p < 0.001)
      and potential uptake of the POPs by breastfed infants may pose adverse health
      hazards.

PMID- 12202935
TI  - Determining demographic effects of cypermethrin in the marine copepod Acartia
      tonsa: stage-specific short tests versus life-table tests.
AB  - Short-term lethal and sublethal responses of the calanoid copepod Acartia tonsa
      to cypermethrin were compared with life-table responses to assess whether or not
      it is necessary to use exposure periods longer than 5 days to estimate
      demographic responses to stress. More specifically, by limiting exposure periods
      to sensitive age classes (eggs, nauplii, copepodids, and adults) and including
      measurements on survival, egg production, and feeding rates, it was possible to
      derive a short test design of similar sensitivity and ecological relevance as
      full life-table tests. Short-term exposures to cypermethrin reduced copepodid's
      feeding rates at concentrations well below those affecting egg production rates
      and survival of eggs and adult stages. Lethal effects on naupliar stages occurred
      at lower concentrations than any other effect observed on eggs and adults. Life
      table sensitivities of the intrinsic rate of increase ( r(m)) to cypermethrin
      were similar to those observed in short-term exposures. More specifically,
      exposure to cypermethrin impaired r(m) responses at concentrations (7.4 ng x L(
      1)) that also affected feeding and naupliar responses. Our results show that by
      quantifying and separating combined toxic effects on ecologically relevant
      individual life-history traits, it is possible to develop toxicity test designs
      of similar ecological relevance yet that are less labor-intensive and costly than
      existing demographic tests.

PMID- 12202937
TI  - Impact on ureteral peristalsis in a stented ureter. An experimental study in the
      pig.
AB  - Peristalsis was examined in ten pigs with stented ureters. In five of the
      animals, the stents were inserted 6-8 weeks before examination, which was
      performed using a 3.5 Ch catheter equipped with thin copper wires in two sites 10
      cm apart. This set-up enabled an analysis of the frequency, direction and
      velocity of the peristaltic waves to be made. When diuresis was gradually raised,
      the frequency and velocity of the contractions usually increased in normal
      ureters, whereas we observed a decline in both of these parameters. There was a
      statistically significant difference in the lower frequency in the long-term
      stented animals. Retrograde peristalsis, aberrant waves and incomplete
      contractions were common in the ureters after prolonged stenting, and urine flow
      was greater around than through the stent. Our results suggest that the flow of
      urine is obstructed by a ureteral stent, and they support clinical data showing
      that such devices prolong the time it takes for a stone to pass to the bladder.

PMID- 12202936
TI  - Long-term effects of partial unilateral ureteral obstruction on renal
      hemodynamics and morphology in newborn rats: a magnetic resonance imaging study.
AB  - We assessed the longitudinal changes in renal vein blood flow (RVBF) and kidney
      volume in response to neonatally induced partial unilateral ureteral obstruction
      (PUUO) in rats with a magnetic resonance imaging (MRI) technique. During
      anesthesia, either the upper third or two thirds of the left ureter was embedded
      into the psoas muscle in newborn rats, creating either a mild (n=20) or a severe
      (n=9) partial obstruction. Control groups consisted of sham-operated (n=12) and
      non-operated (n=15) rats. During the following 24 weeks, RVBF and kidney volume
      were measured sequentially every 2-6 weeks with MRI, beginning 9 days after the
      operation. Both mild and severe obstruction caused a time-dependent decrease in
      RVBF. At week 24, the mean RVBF had decreased to 79% of the controls in the
      mildly obstructed kidneys (mean+/-SE: 1.45+/-0.14 vs 1.84+/-0.08 ml/min/100 g
      body weight, P<0.05) and to 57% of controls in the severely obstructed kidneys
      (1.05+/-0.10 vs 1.84+/-0.08 ml/min/100 g body weight, P<0.05). The renal pelvis
      volume increased and the renal parenchymal volume decreased significantly in the
      severely obstructed kidneys compared to the mildly obstructed kidneys. A good
      correlation was found between kidney volume measured in vivo using MRI and that
      measured in vitro (r>0.8, P<0.05), and between RVBF and renal parenchymal volume
      (r=0.758, P<0.01). In conclusion, the degree of reduction in RVBF depends on the
      severity and the duration of the PUUO. MRI can safely and reliably be used to
      monitor the longitudinal changes in RVBF and kidney volume in rats from early
      life.

PMID- 12202938
TI  - Relationship between clinical data and urodynamic findings in patients with
      lumbar intervertebral disk protrusion.
AB  - The relationship between voiding disturbances and urodynamic diagnosis in
      patients with lumbar intervertebral disk protrusion is controversial. The
      objective of this study was to determine the association between clinical data
      and urodynamic diagnosis, in order to reveal whether bladder dysfunction can be
      assessed on the basis of urological symptoms and signs. We prospectively studied
      122 patients with lumbar intervertebral disk protrusion. Detrusor areflexia was
      found in 32 of these patients, while in the remaining 90 detrusor activity was
      normal. All patients with detrusor areflexia reported difficulty voiding by
      abdominal straining. The patients with normal urodynamic findings were either
      free of voiding disturbances (77 patients) or complained of frequent voiding (13
      patients). In conclusion, there are cases of lumbar intervertebral disk
      protrusion in which the presence of bladder dysfunction can be predicted on the
      basis of clinical urodynamic testing, i.e. clinical neurological alterations,
      decreased bladder sensation, voiding by straining, increased bladder capacity,
      residual volume, and intermittent or continuous low flow curve on free
      uroflowmetry.

PMID- 12202939
TI  - Renal effects on a solitary kidney of specific inhibition of cyclooxygenease-2
      after 24 h of complete ureteric obstruction in rats.
AB  - The purpose of this study is to show whether selective (celecoxib) and non
      selective (piroxicam) inhibitors of COX-2 can alter the morphological and
      functional changes after the release of a 24 h complete ureteric obstruction in
      tissue from solitary rat kidney. Forty male Sprague-Dawley rats weighing 225-250
      g were used. The animals were divided into four groups. In group 1 rats (control,
      n=10), only right nephrectomy was performed. Group 2 rats (untreated, n=10)
      underwent right nephrectomy and the left ureter was completely obstructed. In
      group 3 rats (celecoxib), the same operation was performed as described for group
      2 and than celecoxib was administered by gavage for a period of 24 h. Group 4
      rats (piroxicam) underwent the same operation as described for group 2, then
      piroxicam was administered intramuscularly at least 1 h before the release of the
      for 24 h complete ureteric obstruction. All animals were then prepared for
      functional and histopathological studies. The administration of celecoxib
      produced a significant decrease in blood urea nitrogen levels when compared to
      the animals receiving piroxicam and the animals with no treatment. Moreover,
      celecoxib caused a significant decreased in creatinine levels when compared to
      the untreated group. Urine volume and the urinary sodium values were increased in
      the celecoxib group when compared with the other groups. The administration of
      celecoxib and piroxicam caused a significant decrease in the number of
      interstitial macrophages when compared to the untreated group. The Bowman space
      was significantly increased in the untreated group when compared with the
      celecoxib and the piroxicam groups. These studies indicate that celecoxib may be
      an important factor affecting renal morphological and functional changes after
      the release of a 24 h complete ureteric obstruction.

PMID- 12202940
TI  - Biocompatibility, encrustation and biodegradation of ofloxacine and silver
      nitrate coated poly-L-lactic acid stents in rabbit urethra.
AB  - The purpose of this study was to evaluate the biocompatibility, encrustation and
      biodegradation properties of silver nitrate and ofloxacine blended caprolactone-L
      lactide copolymer coated self-reinforced poly-L-lactic acid (SR-PLLA) urospirals
      in situ in the male rabbit urethra. SR-PLLA urospirals coated with 10% by weight
      silver nitrate or 5% by weight ofloxacine blended copolymer or pure copolymer
      were inserted into the posterior urethra of 18 male rabbits. No prophylactic
      antibiotics were given. The animals were sacrificed 1 or 6 months after
      insertion. Urethral tissue reactions were histologically scored semiquantitavely
      and the appearence of the stents assessed using scanning electron microscopy. The
      biodegradation time of SR-PLLA stents was remarkably reduced by the caprolactone
      coating. Silver nitrate and ofloxacine blended copolymer coated urospirals caused
      less tissue reaction than urospirals with a pure copolymer coating. Silver
      nitrate coating effectively prevented biofilm formation and stent encrustation.
      Silver nitrate and ofloxacine blended copolymer coated SR-PLLA urospirals had
      good biocompatibility properties in rabbit urethra. In particular, coating with
      silver nitrate may provide possibilities of preventing bacterial adhesion to
      bioabsorbable stents.

PMID- 12202941
TI  - The role of LFA-1 in the lysis of bladder cancer cells by bacillus Calmette
      Guerin and interleukin 2-activated killer cells.
AB  - Activated cytotoxic effector cells such as bacillus Calmette-Guerin (BCG)
      activated killer (BAK) and lymphokine-activated killer (LAK) cells are thought to
      mediate the antitumor effects in the immunotherapy of superficial bladder cancer
      with BCG. We investigated the role of the leukocyte-function-antigen-1 and its
      two subunits CD11a and CD18 in the lysis of bladder tumor cells by both effector
      cell populations. We used flow cytometry to measure CD11a and CD18 expression on
      BAK and LAK cells. The involvement of both surface molecules in the lysis of
      bladder tumor cells was determined by phase contrast microscopy and a set of
      radioactive-release assays using specific inhibitory antibodies. BAK and LAK
      cells expressed more CD11a and CD18 on their surfaces than unstimulated
      peripheral blood mononuclear cells. Effector-target cell adhesion was a
      prerequisite for the cell-mediated cytotoxicity of BAK and LAK cells against
      bladder tumor targets. Cytotoxicity of both BAK and LAK cells was inhibited by a
      combination of anti-CD11a and -CD18 monoclonal antibodies. Our study gives
      further insight into the complex interactions of the adhesion molecules of
      activated immune cells and their respective tumor targets and might help to
      increase our knowledge of the molecular mechanisms of BCG-immunotherapy.

PMID- 12202942
TI  - Functions of epidermal growth factor-like growth factors during human urothelial
      reepithelialization in vitro and the role of erbB2.
AB  - Transitional epithelium of the urinary bladder can be damaged during, for
      example, catheterization, overstretching due to obstructed voiding, or partial
      resection. The subsequent repair process can be stimulated by specific proteins
      such as epidermal growth factor (EGF) and transforming growth factor-alpha
      (TGFalpha). However, little is known about the role of EGF-like growth factors
      and their respective receptors in human urothelial repair. In this study, we
      examined the effects of EGF, TGFalpha, amphiregulin and heregulin-alpha
      (HRGalpha) on proliferation, wound closure, and the expression of their receptors
      c-erbB1-c-erbB4 in primary cultures of human urothelial cells in vitro. Under
      conditions representing intact urothelium, all EGF-like growth factors except
      HRGalpha induced proliferation. TGFalpha induced proliferation up to four times.
      Amphiregulin increased expression of c-erbB1. Treatment with either TGFalpha or
      amphiregulin resulted in higher c-erbB1 activation and c-erbB3 levels. None of
      the growth factors affected the constitutive expression of c-erbB2 and c-erbB4.
      In the repair model, both EGF and TGFalpha stimulated the wound closure most
      strongly. This was mainly achieved by increased cellular migration. Receptor
      expression was not affected by the addition of exogenous growth factor. The role
      of c-erbB2 in wound healing was further investigated with the use of antisense
      DNA. Wound closure could be delayed up to 50% by antisense c-erbB2 but not by
      mismatched or sense oligonucleotides. Excessive production (e.g. in bladder
      tumors) or application of EGF, TGFalpha or amphiregulin, but not HRGalpha may
      lead to either hyperplasia or a faster repair of damaged urothelium in vivo.
      These effects seem to be mediated not only via c-erbB1 but also via c-erbB2. Our
      results suggest that modified members of the EGF-EGFR family are potential
      targets for future therapies for bladder wound healing and malignancy.

PMID- 12202943
TI  - Distribution and regional variation of pituitary adenylate cyclase activating
      polypeptide and other neuropeptides in the rat urinary bladder and ureter:
      effects of age.
AB  - The distribution and regional variation of nerves immunoreactive for the
      neuropeptides pituitary adenylate cyclase activating polypeptide (PACAP),
      calcitonin gene-related peptide (CGRP), substance P (SP) and vasoactive
      intestinal polypeptide were investigated in the urinary bladder and distal ureter
      of young adult (3 months) and aged (24 months) male Wistar rats by indirect
      immunohistochemistry. Semi-quantitative estimations of nerve densities were made
      of peptidergic fibres innervating the dome, body and base of the urinary bladder
      and distal ureter. Sensory innervation of the dome was very sparse and the
      overall density of innervation increased progressively towards the base of the
      bladder. The density of innervation in the aged rats was closely comparable to
      that in the young adults, with the exception of slight reductions in CGRP and SP
      innervation of the muscle layer. Moreover, there was a marked reduction in the
      density of PACAP innervation of the subepithelial plexus and of the muscle layer
      of the bladder base. However, radioimmunoassay showed no significant difference
      (P>0.05) in PACAP contents between young and aged rat urinary bladder. In the
      distal ureter of aged rats the densities of innervation by fibres immunoreactive
      for SP and PACAP but not CGRP were reduced. These findings suggest that the level
      of sensory innervation of the bladder and distal ureter are reduced in old age
      and that the afferent limb of voiding reflexes may in consequence be perturbed.

PMID- 12202944
TI  - Ex vivo stimulation of renal transport of the cytostatic drugs methotrexate,
      cisplatin, topotecan (Hycamtin) and raltitrexed (Tomudex) by dexamethasone, T3
      and EGF in intact human and rat kidney tissue and in human renal cell carcinoma.
AB  - Previous experiments have shown that both in vivo and in vitro pre-treatment with
      various hormones increases the renal transport capacity for weak organic acids,
      such as PAH, in rats. The aim of the present study was to test whether or not
      accumulation of the anticancer drugs methotrexate (MTX), cisplatin (CP),
      raltitrexed (Tomudex) and topotecan (Hycamtin) can be increased in intact,
      healthy rat and human renal cortical slices and in human renal cell carcinoma
      (RCC). Intact, healthy human tissue was obtained from tumour bearing kidneys of
      patients suffering from RCC. Experiments were intended as a new approach to
      overcome so-called multidrug resistance. Kidney tissue slices were incubated for
      24 h in William's medium E containing various concentrations of dexamethasone,
      T(3), or EGF. Thereafter slices were placed in anticancer drug containing Cross
      Taggart medium and the drug uptake into kidney tissue was measured for 2 h. In
      intact rat and human renal tissue slices, the uptake of p-aminohippurate (PAH =
      reference substance) increased significantly after incubation in dexamethasone
      containing medium (134% and 156%, respectively). There were no stimulating
      effects of either T(3) or EGF on PAH accumulation. On the other hand, only the
      accumulation of MTX, but not of CP, raltitrexed or topotecan, was significantly
      enhanced after hormone pre-treatment both in intact renal tissue and in RCC. A
      stimulation of renal PAH accumulation can be performed ex vivo, as reported
      previously, both in intact rat and human renal cortical slices and in RCC.
      Discrepancies between the effects of dexamethasone and T(3) or EGF indicate
      different modes of action of these substances at the cellular level.
      Unfortunately, with the exception of MTX, the uptake of anticancer drugs can not
      be stimulated effectively ex vivo in human RCC tissue by the substances used.
      Evidently the transport of these anticancer drugs out of the kidney cells is more
      effective than their uptake.

PMID- 12202945
TI  - Relationship between seminal plasma interleukin-6 and tumor necrosis factor alpha
      levels with semen parameters in fertile and infertile men.
AB  - The levels of two proinflammatory cytokines, namely tumor necrosis factor alpha
      (TNF-alpha) and interleukin 6 (IL-6), were investigated in seminal plasma (SP) of
      proven fertile (n=24) and infertile (n=55) men to evaluate the relationship
      between diagnosis and semen parameters in a prospective study. Infertile men were
      divided into four groups as follows: (1) varicocele (n=23), (2) 3 months after
      varicocelectomy (post-varicocele, n=14), (3) male accessory gland infection
      (MAGI, n=10) and (4) bilateral testicular atrophy (n=8). IL-6 and TNF-alpha
      levels were similar in the SP of fertile and infertile men. There was a strong
      correlation between the levels of TNF-alpha and IL-6 in all groups (P<0.001). IL
      6 levels were not correlated with seminal parameters (P>0.05). TNF-alpha levels
      were negatively correlated with the sperm motility and morphology (P<0.05), but
      there was no correlation with total sperm counts (P>0.05). The mean levels of IL
      6 in the SP of the MAGI group was higher than in the other groups but did not
      reach statistical significance. No variation was found in the SP levels of the
      proinflammatory cytokines studied between the varicocele and the post-varicocele
      groups. Our results suggest that IL-6 and TNF-alpha are involved in male
      fertility. However, their measurement in SP seem to be unsuitable for routine
      infertility work, perhaps with the exception of men with inflammatory genital
      diseases.

PMID- 12202946
TI  - Tourniquet application and epinephrine injection to penile skin: is it safe?
AB  - Although a tourniquet is frequently used in penile surgery there is still no
      consensus on safe application time. The aim of the present study is to
      investigate the effect of malondialdehyde (MDA) levels and histological changes
      in skin flaps after penile tourniquet application and epinephrine injection. A
      total of 36 male white New Zealand rabbits were randomly divided into six groups
      each containing six animals. A Mathieu-like flap was raised in all of the groups
      and a tourniquet was applied and the penis was subjected to ischemia for 10, 20
      and 40 min in groups 1, 2 and 3, respectively. The flaps were then allowed to
      reperfuse for 5 min. Biopsies for MDA measurement were harvested in these groups.
      Subcutaneous 1/200,000 epinephrine was injected into penile skin in group 4 and 5
      rabbits and biopsies for MDA measurement were harvested 10 and 40 min after
      injection. The control group was anesthetized without tourniquet usage or
      epinephrine injection. Specimens taken from the harvested flaps of all groups
      were submitted for histological evaluation. The mean MDA levels in all
      experimental groups were higher than in the control group and the difference was
      statistically significant. Edema, congestion and extravasation were observed in
      groups 1, 2 and 3. Minimal congestion and edema were observed in group 4 and
      severe edema and extravasation in group 5. Tourniquet usage for a duration of
      less than 10 min is clearly safer than prolonged usage. Epinephrine injection to
      penile skin may show a deleterious effect on wound healing.

PMID- 12202947
TI  - Serratia marcescens hemolysin (ShlA) binds artificial membranes and forms pores
      in a receptor-independent manner.
AB  - Both the inactive and active conformations of the hemolysin/cytolysin of Serratia
      marcescens (ShlA) binds membranes of erythrocytes, but only active ShlA is able
      to form pores. ShlA is unable to lyse prokaryotic membranes. To determine the
      receptors of the binding and pore-forming domains of active cytolysin on
      eukaryotic membranes, artificial large unilamellar vesicles (LUVs) of various
      membrane compositions were examined. In the current study, it is shown that
      significant pore formation and lysis was achieved with binary
      phosphatidylcholine/phosphatidylserine (PS) liposomes. No proteinaceous receptor
      was needed for either binding or pore formation by ShlA. Membrane integration and
      pore-forming activity were enhanced by addition of phosphatidylethanolamine.
      Phosphatidylserine is negatively charged at physiologic pH and is almost absent
      in prokaryotic membranes. Hence, membrane binding and insertion of ShlA are
      highly dependent on phosphatidylserine, which targets the toxic activity to
      eukaryotic cell membranes without any need of a proteinaceous receptor. This may
      explain why prokaryotic membranes were found to be resistant against ShlA in a
      previous study.

PMID- 12202948
TI  - Effect of anion transport blockers on CFTR in the human sweat duct.
AB  - Cystic fibrosis transmembrane conductance regulator (CFTR) is a protein kinase A
      (PKA) and ATP regulated Cl- channel. Studies using mostly ex vivo systems
      suggested diphenylamine-2-carboxylate (DPC), 5-nitro-2-(3-phenylpropylamino)
      benzoic acid (NPPB) and glybenclamide inhibit CFTR Cl- conductance (CFTR GCl).
      However, the properties of inhibition in a native epithelial membrane have not
      been well defined. The objective of this study was to determine and compare the
      inhibitory properties of the aforementioned inhibitors as well as the
      structurally related anion-exchange blockers (stilbenes) including 4,4'
      diisothiocyanatostilbene-2,2'-disulfonic acid (DIDS), 4-acetamido-4'
      isothiocyanatostilbene-2,2'-disulfonic acid (SITS), 4,4'-dinitrostilbene-2,2'
      disulfonic acid (DNDS) in the microperfused intact and basilaterally
      permeabilized native sweat duct epithelium. All of these inhibitors blocked CFTR
      in a dose-dependent manner from the cytoplasmic side of the basilaterally
      permeabilized ducts, but none of these inhibitors blocked CFTR GCl from the
      luminal surface. We excluded inhibitor interference with a protein kinase
      phosphorylation activation process by "irreversibly" thiophosphorylating CFTR
      prior to inhibitor application. We then activated CFTR GCl by adding 5 mM ATP. At
      a concentration of 10(-4) M, NPPB, DPC, glybenclamide, and DIDS were equipotent
      and blocked approximately 50% of irreversibly phosphorylated and ATP-activated
      CFTR GCl (DIDS = 49 +/- 10% > NPPB = 46 +/- 10% > DPC = 38 +/- 7% > glybenclamide
      = 34 +/- 5%; values are mean +/- SE expressed as % inhibition from the control).
      The degree of inhibition may be limited by inhibitor solubility limits, since
      DIDS, which is soluble to 1 mM concentration, inhibited 85% of CFTR GCl at this
      concentration. All the inhibitors studied primarily blocked CFTR from the
      cytoplasmic side and all inhibition appeared to be independent of metabolic and
      phosphorylation processes.

PMID- 12202949
TI  - Lysine uptake by cloned hCAT-2B: comparison with hCAT-1 and with trophoblast
      surface membranes.
AB  - To study the cationic amino-acid transporter hCAT-2B of human placenta, total RNA
      was harvested from primary cultured trophoblast and from the BeWo choriocarcinoma
      cell line (b30 clone) and used for reverse transcription (RT) and polymerase
      chain reaction (PCR). Primers based on published sequences identified expression
      of mRNA for hCAT-2B. RT-PCR yielded a 2.06 kb hCAT-2B cDNA, which was cloned.
      hCAT-2B cRNA injection into Xenopus laevis oocytes stimulated saturable lysine
      uptake (Km approximately 125 mM). In the presence of Na+, uptake was completely
      inhibited by L-arginine but only partially by neutral amino acids. To compare
      directly the interaction of hCAT-1 and hCAT-2B with neutral amino acids and
      sodium, we examined the inhibition of these transporters by L-leucine and L
      alanine over a wide concentration range. L-Alanine and L-leucine inhibit uptake
      by hCAT-2B substantially less completely than uptake by hCAT-1. The interaction
      of hCAT-2B resembles that of system y+ in the microvillous membrane of human
      placenta, while that of hCAT-1 is more comparable to that of system y+ in basal
      membrane. The identification and characterization of the various cationic amino
      acid transporters of the human placenta have the potential to increase the
      understanding of the cellular mechanism of transplacental transfer.

PMID- 12202950
TI  - Evidence for segregation of heterologous GPI-anchored proteins into separate
      lipid rafts within the plasma membrane.
AB  - Cholesterol and glycosphingolipid-rich membrane rafts, which are rich in GPI
      anchored proteins and are distinct from caveolae, are believed to serve as
      platforms for signal transduction events and protein recycling. GPI-anchored
      proteins with diverse functions as well as caveolin may be recovered in a
      membrane fraction insoluble in cold non-ionic detergent. This study tests for
      possible heterogeneity in the protein composition of the lipid rafts and
      detergent-insoluble membrane complexes by examining the two GPI-anchored
      homologous human folate receptors (FR)-alpha and -beta, the GPI-anchored human
      placental alkaline phosphatase (PLAP), and caveolin (control) in transfected CHO
      cells. Both FR and PLAP showed the equal distribution of cell-surface vs.
      sequestered (recycling) protein typical of GPI-proteins. Quantitative affinity
      purification of detergent-insoluble complexes using biotinylated folate or
      specific antibodies demonstrated a strong association of the homologous FR-alpha
      and FR-beta in the same detergent-insoluble complex and separate complexes
      containing either PLAP or caveolin. Immunogold localization experiments using
      antibody crosslinking to produce larger aggregates of GPI-anchored proteins for
      visualization by electron microscopy also showed a clear separation between FR-
      and PLAP-rich membrane microdomains. Thus, even though functionally diverse and
      heterologous GPI-anchored proteins are known to share endocytic and recycling
      vesicles, they may be segregated in distinct lipid rafts on the basis of their
      ecto(protein) domains facilitating clustering, compartmentalization and homotypic
      protein interactions.

PMID- 12202951
TI  - Intracellular delivery of trehalose into mammalian cells by
      electropermeabilization.
AB  - The disaccharide trehalose is increasingly being used as a very efficient
      stabilizer of cells, membranes and macromolecules during cryo- and
      lyoconservation. Although extracellular trehalose can reduce cryo- and lyodamage
      to mammalian cells, the sugar is required on both sides of the plasma membrane
      for maximum protection efficiency. In the present study, mouse myeloma cells were
      loaded with the disaccharide by means of reversible electropermeabilization in
      isotonic trehalose-substituted medium, which contained 290 mM trehalose as the
      major solute. By using the membrane-impermeable fluorescent dye propidium iodide
      as the reporter molecule, optimum electropulsing conditions were found, at which
      most permeabilized cells survived and recovered (i.e., resealed) their original
      membrane integrity within a few minutes after electric treatment. Microscopic
      examination during the resealing phase revealed that electropulsed cells shrank
      gradually to about 60% of their original volume. The kinetics of the dye uptake
      and the volumetric response of cells to electropulsing were analyzed using a
      theoretical model that relates the observed cell volume changes to the solute
      transport across the transiently permeabilized cell membrane. From the best fit
      of the model to the experimental data, the intracellular trehalose concentration
      in electropulsed cells was estimated to be about 100 mM. This loading efficiency
      compares favorably to other methods currently used for intracellular trehalose
      delivery. The results presented here point toward application of the
      electropermeabilization technique for loading cells with membrane-impermeable
      bioprotectants, with far-reaching implications for cryo- and lyopreservation of
      rare and valuable mammalian cells and tissues.

PMID- 12202952
TI  - Single ionic channels of two Caenorhabditis elegans chemosensory neurons in
      native membrane.
AB  - The genome of Caenorhabditis elegans contains representatives of the channel
      families found in both vertebrate and invertebrate nervous systems. However, it
      lacks the ubiquitous Hodgkin-Huxley Na+ channel that is integral to long-distance
      signaling in other animals. Nematode neurons are presumed to communicate by
      electrotonic conduction and graded depolarizations. This fundamental difference
      in operating principle may require different channel populations to regulate
      transmission and transmitter release. We have sampled ionic channels from the
      somata of two chemosensory neurons (AWA and AWC) of C. elegans. A Ca2+-activated,
      outwardly rectifying channel has a conductance of 67 pS and a reversal potential
      indicating selectivity for K+. An inwardly rectifying channel is active at
      potentials more negative than -50 mV. The inward channel is notably flickery even
      in the absence of divalent cations; this prevented determination of its
      conductance and reversal potential. Both of these channels were inactive over a
      range of membrane potentials near the likely cell resting potential; this would
      account for the region of very high membrane resistance observed in whole-cell
      recordings. A very-large-conductance (> 100 pS), inwardly rectifying channel may
      account for channel-like fluctuations seen in whole-cell recordings.

PMID- 12202953
TI  - Mechanisms of activation of NHE by cell shrinkage and by calyculin A in Ehrlich
      ascites tumor cells.
AB  - The Na+/H+ exchanger isoforms NHE1, NHE2, and NHE3 were all found to be expressed
      in Ehrlich ascites tumor cells, as evaluated by Western blotting and confocal
      microscopy. Under unstimulated conditions, NHE1 was found predominantly in the
      plasma membrane, NHE3 intracellularly, and NHE2 in both compartments. Osmotic
      cell shrinkage elicited a rapid intracellular alkalinization, the sensitivity of
      which to EIPA (IC50 0.19 microM) and HOE 642 (IC50 0.85 microM) indicated that it
      predominantly reflected activation of NHE1. NHE activation by osmotic shrinkage
      was inhibited by the protein kinase C inhibitors chelerythrine (IC50 12.5
      microM), Go 6850 (5 microM), and Go 6976 (1 microM), and by the p38 MAPK
      inhibitor SB 203580 (10 microM). Furthermore, hypertonic cell shrinkage elicited
      a biphasic increase in p38 MAPK phosphorylation, with the first significant
      increase detectable 2 minutes after the hypertonic challenge. Neither myosin
      light chain kinase-specific concentrations of ML-7 (IC50 40 microM) nor ERK1/2
      inhibition by PD 98059 (50 microM) had any effect on NHE activation. Under
      isotonic conditions, the serine/threonine protein phosphatase inhibitor calyculin
      A elicited an EIPA- and HOE 642-inhibitable intracellular alkalinization,
      indicating NHE1 activation. Similarly, shrinkage-induced NHE activation was
      potentiated by calyculin A. The calyculin A-induced alkalinization was not
      associated with an increase in the free, intracellular calcium concentration, but
      was abolished by chelerythrine. It is concluded that shrinkage-induced NHE
      activation is dependent on PKC and p38 MAPK, but not on MLCK or ERK1/2. NHE
      activity under both iso- and hypertonic conditions is increased by inhibition of
      serine/threonine phosphatases, and this effect appears to be PKC-dependent.

PMID- 12202954
TI  - Quantitative trait loci for bone density in mice: the genes determining total
      skeletal density and femur density show little overlap in F2 mice.
AB  - Bone mineral density variation is a highly heritable trait and is the best
      predictor of skeletal fragility. Total skeletal density was determined by
      PIXIMUS, and femur density was determined by pQCT. The data were analyzed for
      quantitative trait loci (QTL) to determine if bone density at a specific skeletal
      site (femur) would identify new gene loci or the same gene loci as total body
      (PIXIMUS). In order to show concordance and differences in QTL for total body
      bone density versus femur bone density, we performed a genome-wide scan from 633
      (MRL x SJL) F2 mice. The bone mineral density (BMD) data from pQCT were used to
      identify nine QTL on chromosomes 1, 3, 4, 9, 12, 17, and 18, while nine QTL on
      chromosomes 1, 2, 4, 9, 11, 14, and 15 were identified by PIXIMUSdata, accounting
      for 32.5% and 30.4% variation in F2 mice, respectively. QTL on chromosomes 1, 2,
      3, 9, 11, 12, 14, 15, 17, and 18 are unique to our study, as they have never been
      described before. Chromosome 1 (D1Mit33 and D1Mit362) had similar QTL between
      pQCT and PIXIMUS. Several QTL were identified for both femur and total body BMD
      but only two QTL were common for both of these phenotypes. This suggests that
      genes regulating bone density differ depending on the skeletal site analyzed.

PMID- 12202955
TI  - The immunosuppressant rapamycin, alone or with transforming growth factor-beta,
      enhances osteoclast differentiation of RAW264.7 monocyte-macrophage cells in the
      presence of RANK-ligand.
AB  - Immunosuppressant therapy is known to cause bone loss. Since this may partly
      result from direct effects on osteoclast development, we investigated whether
      cyclosporin A (CsA), rapamycin, or FK506 affect osteoclastic differentiation of
      RAW264.7 monocytic cells induced by RANK-ligand (RANKL). Furthermore, since the
      rapamycin receptor protein binds transforming growth factor beta (TGF-beta)
      receptors, and TGF-beta enhances osteoclastogenesis induced by RANKL, we also
      examined potential synergistic effects of rapamycin and TGF-beta1. Rapamycin
      inhibited cell proliferation and stimulated tartrate-resistant acid phosphatase
      (TRAP) activity of RAW cells in a dose-dependent manner. At the optimal
      concentration of 10 ng/ml, it increased the number of TRAP+ multinucleated cells
      (MNC) more than 20-fold and enhanced the expression of TRAP and calcitonin
      receptor (CTR) mRNAs 2.1- and 10-fold, respectively. CsA, at 125-2000 ng/ml,
      similarly inhibited proliferation, but at high doses (1000-2000 ng/ml) it
      decreased TRAP activity, TRAP+MNC formation, and the expression of TRAP and CTR
      mRNAs. FK506 had no effect on cell proliferation or TRAP activity at
      concentrations up to 2000 ng/ml; however, like CsA, 1000 ng/ml FK506 inhibited
      TRAP+MNC formation and the expression of TRAP and CTR mRNAs. The combination of
      rapamycin (10 ng/ml) and TGF-beta1 (1 ng/ml) increased TRAP+MNC 3.1- and 6.9-fold
      as compared with rapamycin or TGF-beta1 alone, respectively, and enhanced CTR
      mRNA expression induced by TGF-beta1 by 1.9-fold. Rapamycin also increased
      osteoclastic resorption activity by 6.5-fold compared with control, and this was
      enhanced further by the addition of TGF-beta by 3-fold, compared with rapamycin
      alone. These data thus indicate that rapamycin, alone or in synergy with TGF
      beta, directly enhances osteoclastogenesis and may affect bone metabolism in vivo
      after long-term use.

PMID- 12202956
TI  - Intrauterine exposure to a maternal low protein diet reduces adult bone mass and
      alters growth plate morphology in rats.
AB  - Epidemiological studies suggest that poor growth during fetal life and infancy is
      associated with decreased bone mass in adulthood. However, theses observations
      have not, to date, been corroborated in animal models. To address this issue we
      evaluated the influence of maternal protein restriction on bone mass and growth
      plate morphology among the adult offspring, using a rat model. Maternal protein
      restriction resulted in a reduction in bone area and BMC, but not BMD, among the
      offspring in late adulthood. The widened epiphyseal growth plate in the protein
      restricted offspring is compatible with the programming of cartilage and bone
      growth by maternal nutrition in early life.

PMID- 12202957
TI  - Distribution of bone mineral density at the proximal tibia in knee
      osteoarthritis.
AB  - One hundred and thirteen knees with osteoarthritis (OA) were studied to assess
      the distribution of bone mineral density (BMD) in the proximal tibia and the
      potential relation between osteoarthritis and osteoporosis in evaluating hip BMD.
      All patients had severe knee pain and were diagnosed with Kellgren and Lawrence
      grade IV osteoarthritis. According to the magnitude of the axial deformity, four
      categories were created: varus>10 degrees ( 28.3%), varus 4-10 degrees (38.9%),
      aligned 180 +/- 3 degrees (13.3%), and valgus>4 degrees (19.5%). For each
      category, the medial and lateral proximal tibial density were assessed. BMD was
      measured at the femoral neck and at 14 regions of interest (ROI) in the proximal
      part of the tibia using dual X-ray absorptiometry. Based on the femoral neck BMD,
      patients were classified according to the World Health Organization (WHO)
      definition of osteoporosis. The mean knee BMD was positively correlated with the
      hip BMD value (knee BMD m = 0.38 + 0.73 x hip BMD, r = 0.60, P<0.001). The knee
      BMD distribution of the 113 patients was negatively correlated with the axial
      deformity (BMD MT-LT = 5.15 - 0.027 x HKA, r = 0.77, P<0.0001). In the varus
      deformity, BMD of the medial side was higher than that of the lateral side with
      an important asymmetry (0.587 g/cm2). This asymmetry was also found in the valgus
      deformity for the lateral side but was less important (-0.112 g/cm2). With equal
      deformity, the asymmetry of BMD was higher in varus deformity (0.587 g/cm2) than
      in valgus deformity (-0.112 g/cm2). Asymmetry of the knee BMD distribution
      revealed that progression of the deformity (either varus or valgus) with joint
      space narrowing led to an increase in the medio-lateral difference of the
      proximal tibia density. Lesser severity of Kellgren and Lawrence grades may
      reveal different results. Twenty patients with osteoporosis developed knee
      osteoarthritis (OA) and the relation between osteoporosis and knee OA remains
      unclear.

PMID- 12202958
TI  - Insulin-like growth factor binding proteins 4 and 5 and bone mineral density in
      elderly men and women.
AB  - Insulin-like growth factor-1 (IGF-I) plays a central role in the maintenance of
      bone mass. To test whether two major IGF-I binding proteins, IGFBP-4 and IGFBP-5,
      are related to bone mineral density (BMD), we studied a sample of the Framingham
      Offspring Cohort participants (99 men and 101 women, ages 60-87). Serum levels of
      IGF-I, IGFBP-4, and IGFBP-5 were measured by previously validated
      radioimmunoassays (CVs approximately 10%). BMDs of the proximal femur and lumbar
      spine were measured using a Lunar DPX-L densitometer. In males, but not females,
      IGF-I and IGFBP-5 were inversely associated with age (r = 0.34 and r = -0.28,
      respectively; P <0.01), while IGFBP-4 levels were positively associated with age
      (P <0.01). Multivariate means for BMD (adjusted for age, body mass index, height,
      smoking, and in women, estrogen use) were computed across quartiles of IGFBP-4
      and IGFBP-5 and IGFBP-4/IGFBP-5 ratio. In women, but not men, IGFBP-5 was
      positively associated with femoral neck BMD (P = 0.03), however, after
      statistical adjustment for IGF-I, this association was no longer significant. No
      other associations were observed for BMD at any other site. Further study is
      necessary for elucidation of the gender differences in the possible influence of
      IGF system components on bone mass.

PMID- 12202959
TI  - Do animal models of anxiety predict anxiolytic-like effects of antidepressants?
AB  - Chronically administered antidepressant drugs, particularly selective serotonin
      (5-HT) reuptake inhibitors (SSRIs), are clinically effective in the treatment of
      all anxiety disorders, while the clinical effectiveness of "traditional"
      anxiolytics, such as benzodiazepines (BDZs), is limited to generalised anxiety
      disorder or acute panic attacks. This implies that animal models of anxiety
      should be sensitive to SSRIs and other antidepressants in order to have
      predictive validity. We reviewed the literature on the effects of antidepressants
      in the so-called animal models of anxiety and found that only the isolation
      induced calls in guinea-pig pups may reveal anxiolytic-like action of all
      antidepressant classes after acute administration. Some other models, such as
      marble-burying or conditioned-freezing behaviours, and isolation- or shock
      induced ultrasonic vocalisation models, may detect anxiolytic-like activity of
      acutely administered antidepressants, although the sensitivity of these models is
      usually limited to SSRIs and other drugs affecting 5-HT uptake. The predictive
      validity of models of "anxiety", such as the plus-maze and light-dark transition
      tests or stress-induced hyperthermia, appears to be limited to BDZ-related drugs.
      Far less work has been done on chronic administration of antidepressants in
      animal anxiety models. Unless and until such studies have been undertaken, the
      true predictive value of the anxiety models will remain unknown.

PMID- 12202960
TI  - Stimulation of serotonin1B receptors induces conditioned place aversion and
      facilitates cocaine place conditioning in rats.
AB  - RATIONALE: Changes in serotonin(1B) (5-HT(1B)) receptor function appear to modify
      the reinforcing properties of cocaine, but the direction of this effect is not
      completely clear. Pharmacological stimulation of 5-HT(1B) enhanced the rewarding
      properties of self-administered cocaine while attenuating the threshold-reducing
      effect of cocaine in the intracerebral brain stimulation procedure. OBJECTIVE:
      The present study investigates how pharmacological modification of 5-HT(1B)
      receptor-mediated neurotransmission influence cocaine motivational properties in
      the conditioned place preference paradigm in rats. METHODS: In separate groups of
      rats the motivational properties of CP 94,253, a selective 5-HT(1B) agonist, or
      GR 127935, a 5-HT(1B/D) receptor partial agonist, given alone or in combination,
      were determined. To evaluate their influence on cocaine-induced place
      conditioning, CP 94,253, that was found to be aversive, was given every day
      before each conditioning session, while GR 127935, which given alone had no
      effect, was administered only before cocaine conditioning sessions. RESULTS: CP
      94,253, injected IP at 2.5 and 10 (but not 0.5) mg/kg produced place aversion in
      the place conditioning paradigm. The aversive effect of 2.5 mg/kg CP 94,253 was
      completely reversed by 10 mg/kg SC GR 127935. Given before every conditioning
      session, CP 94,253 did not modify place conditioning by four injections of 10
      mg/kg cocaine but at 2.5 mg/kg it potentiated a sub-threshold dose of cocaine.
      The place preference caused by these two drugs was completely reversed by 10
      mg/kg GR 127935. The antagonism by GR 127935 of CP 94,253's effects was shown not
      to be due to the induction of state-dependent effects. CONCLUSION: The results
      suggest that stimulation of 5-HT(1B) receptors causes place aversion, and
      enhances the effect of low doses of cocaine in the conditioned place preference
      paradigm.

PMID- 12202962
TI  - Effect of CGP39551 administration on the kindling of ethanol-withdrawal seizures.
AB  - RATIONALE: It has previously been shown that drugs, such as benzodiazepines, that
      inhibit seizure activity during ethanol withdrawal, fail to alleviate the
      potentiated withdrawal seen following repeated episodes of withdrawal when
      administered during each withdrawal episode. Acute administration of the N-methyl
      D-aspartate (NMDA) receptor competitive antagonist, CGP39551, has been shown to
      inhibit seizure activity during ethanol withdrawal, and, when administered during
      the periods of repeated diazepam withdrawal, it blocked the reduction in
      pentylenetetrazol (PTZ) seizure threshold seen following a final, untreated
      withdrawal. OBJECTIVES: The aim of the current study was to determine if CGP39551
      could alter final ethanol-withdrawal symptoms when administered during the acute
      intermittent withdrawal periods. METHODS: Mice were chronically treated with
      ethanol-containing liquid diet for either 30 days continuously (single
      withdrawal) or with 8-h withdrawal periods on day 16 and day 23 of treatment
      (repeated withdrawal). Control animals received a control diet for the same
      period of time. On the final withdrawal animals were tested for behavioural signs
      of withdrawal. The effect of CGP39551 administered acutely on withdrawal [up to 5
      mg/kg, intraperitoneally (i.p.)] or during the intermittent withdrawal periods
      (10 mg/kg, i.p.) was examined. RESULTS: Acute administration of CGP39551 failed
      to inhibit handling-induced convulsions in the single-withdrawal or repeated
      withdrawal group and had no effect on either decreased exploration or increased
      sensitivity to PTZ seen in withdrawal. Surprisingly, when CGP39551 was
      administered during periods of repeated ethanol withdrawal a potentiation of
      seizure activity was seen in the final, untreated withdrawal. This potentiation
      of seizure activity, compared with vehicle-treated animals, was not seen when
      CGP39551 was given whilst animals had access to ethanol (single-withdrawal group
      and repeated-withdrawal group where CGP39551 treatment was non-contingent with
      withdrawal episodes). However, the decrease in exploration seen during withdrawal
      was potentiated in repeated-withdrawal animals treated with CGP39551 irrespective
      of the time at which the CGP39551 was administered. CONCLUSIONS: Treatment with
      an NMDA receptor-competitive antagonist potentiated the ethanol-withdrawal
      syndrome in animals with previous experience of ethanol withdrawal.

PMID- 12202961
TI  - Effects of reboxetine, a selective norepinephrine reuptake inhibitor, on
      sympathetic and parasympathetic outflow to the heart: preliminary data.
AB  - RATIONALE: Antidepressants exert distinct effects on cardiac autonomic nervous
      system (ANS) function, depending on their receptor profile. Reboxetine is a
      selective norepinephrine (NE) reuptake inhibitor and shows only low affinity for
      adrenergic and muscarinic receptors. Data on reboxetine's effects on ANS function
      in patients with major depression (MD) are sparse. OBJECTIVE: This study
      evaluates the effects of reboxetine on cardiac ANS function assessed by
      standardized measurements of heart rate variability (HRV). METHODS: Twenty-five
      MD patients (DSM-III-R) underwent serial ANS function tests ( n = 94) including
      conventional electrocardiograms and standardized measurements of HRV and blood
      pressure prior to reboxetine treatment as well as on days 2, 10 and 21 during
      reboxetine therapy. The starting dose was 4 mg; on day 10, reboxetine was
      increased to 8 mg/day. The effects of reboxetine on ANS function were evaluated
      using the paired Wilcoxon test. RESULTS: Reboxetine treatment was associated with
      1) a significant decrease in absolute and relative low-frequency power as well as
      in mean arterial pressure on day 2, and 2) a significant decrease in the average
      low- to high-frequency ratio on days 2 and 10. No significant changes in any of
      the vagally mediated HRV indices occurred. CONCLUSION: These preliminary findings
      are compatible with the hypothesis that inhibition of brain NE reuptake by
      reboxetine resulted in an inhibition of central noradrenergic activity via a
      local increase of NE concentration at inhibitory alpha(2)-autoreceptors. Long
      term treatment (21 days) may cause desensitization and down-regulation of
      alpha(2)-autoreceptors, so that attenuation of the inhibitory restraint on
      sympathetic outflow results.

PMID- 12202963
TI  - Neuropsychological performance and noradrenaline function in chronic fatigue
      syndrome under conditions of high arousal.
AB  - RATIONALE: Subjective and objective impairments in neuropsychological function
      have been reported in chronic fatigue syndrome (CFS) patients under conditions of
      high arousal. These impairments may reflect impaired central noradrenaline
      function such as impaired post-synaptic alpha-2 adrenoceptor function.
      OBJECTIVES: To determine whether high-dose clonidine has greater agonist effects
      at central post-synaptic alpha-2 receptors in CFS patients than controls under
      conditions of high arousal. As a result clonidine may reverse neuropsychological
      deficits underlying symptoms of poor concentration and memory. METHODS: High-dose
      clonidine (2.5 mg/kg) and placebo challenge tests were given in random order to
      ten medication-free CFS patients without anxiety disorders, depressive disorders
      or migraine and ten matched healthy controls under the same stressors (timed
      neuropsychological testing, venous sampling, intravenous drug administration).
      Growth hormone, cortisol, blood pressure, pulse rate, visual analogue scales of
      subjective neuropsychological performance and the performance on several tests
      from a computerised neuropsychological battery were measured. RESULTS: In CFS
      patients versus controls, clonidine enhanced both growth hormone ( P = 0.028) and
      cortisol release ( P = 0.021) and increased speed in the initial stage of a
      planning task ( P = 0.023). There were no other differences between CFS patients
      and controls on hormonal, physiological, symptomatic or neuropsychological
      measures. CONCLUSIONS: Under conditions of high arousal, CFS patients may display
      supersensitive central post-synaptic alpha-2 adrenoceptor function associated
      with the release of cortisol and growth hormone and initial thinking time in
      planning tasks.

PMID- 12202964
TI  - Mild opioid deprivation increases the degree that opioid-dependent outpatients
      discount delayed heroin and money.
AB  - RATIONALE: A growing literature suggests that excessive temporal discounting of
      delayed rewards may be a contributing factor in the etiology of substance abuse
      problems. Little is known, however, about how drug deprivation may affect
      temporal discounting of delayed rewards by drug-dependent individuals. OBJECTIVE:
      To examine the extent to which opioid deprivation affects how opioid-dependent
      individuals discount small, medium and large quantities of delayed heroin and
      money. METHODS: Thirteen opioid-dependent individuals maintained on buprenorphine
      completed a hypothetical choice task in which they choose between a constant
      delayed reward amount and an immediate reward amount that was adjusted until they
      expressed indifference between both outcomes. The task was completed for three
      values of heroin and money rewards during eight sessions under conditions of
      opioid deprivation (four sessions) and satiation (four sessions). RESULTS: Across
      conditions, hyperbolic functions provided a good fit for the discounting data.
      Degree of discounting was significantly higher when subjects were opioid
      deprived. Consistent with previous findings, degree of discounting was higher for
      heroin than money and inversely related to the magnitude of the reward.
      CONCLUSION: Opioid deprivation increased the degree to which dependent
      individuals discounted delayed heroin and money. Understanding the conditions
      that affect how drug-dependent individuals discount delayed rewards might help us
      understand the myopic choices made by such individuals and help improve treatment
      outcomes.

PMID- 12202965
TI  - Influence of gonadectomy on the antinociceptive effects of opioids in male and
      female rats.
AB  - RATIONALE: Sex differences in the antinociceptive effects of opioids have been
      reported in a variety of nociceptive assays, and it has been postulated that
      these differences are mediated by gonadal hormones. OBJECTIVES: The present study
      examined the influence of gonadectomy on opioid antinociception in male and
      female rats. METHODS: In a warm-water, tail-withdrawal procedure, the
      antinociceptive effects of the high-efficacy micro opioids etorphine and
      morphine; the low-efficacy micro opioids buprenorphine and dezocine; and the low
      efficacy, mixed-action opioids butorphanol and nalbuphine were examined in intact
      and gonadectomized rats of the F344 and Sprague Dawley (SD) strains. RESULTS: The
      opioids examined were generally more potent in producing an antinociceptive
      effect in intact males than intact females, with larger sex differences observed
      with the less-effective opioids. In F344 males, gonadectomy produced small
      decreases in the potency of etorphine and morphine, and large decreases in the
      potency of buprenorphine, dezocine, butorphanol, and nalbuphine. Similar effects
      were obtained in SD males, with gonadectomy decreasing the potency of each of the
      opioids tested. In F344 females, gonadectomy produced small increases in the
      potency of etorphine and large increases in the potency of buprenorphine,
      dezocine, butorphanol, and nalbuphine. A similar effect was obtained in SD
      females, as gonadectomy increased the potency of etorphine, morphine, and
      buprenorphine. In both sexes, gonadectomy had a greater effect in F344 than SD
      rats. CONCLUSIONS: These findings suggest that gonadectomy decreases opioid
      antinociception in male rats and increases opioid antinociception in female rats.
      Additionally, the influence of gonadectomy on opioid antinociception appears to
      be determined by the relative effectiveness of the opioid tested and the rodent
      strain used.

PMID- 12202966
TI  - Sex differences in the subjective and reinforcing effects of cigarette nicotine
      dose.
AB  - RATIONALE: Some research with novel nicotine delivery methods suggests that
      nicotine itself may be less reinforcing in women than in men. However, sex
      differences in the reinforcing effects of nicotine dose via cigarette smoking
      have received little attention. OBJECTIVES: Sex differences in the subjective and
      reinforcing effects of smoking were examined as a function of two cigarette
      nicotine "dose" levels (moderate - subjects' preferred brand, > or = 0.7 mg
      yield; low - Carlton "ultra-light", 0.1 mg yield). METHODS: Male and female
      smokers ( n = 30) participated in three sessions, the first two involving
      independent assessment (only one brand available), and the third involving
      concurrent assessment (both brands available), of subjective ratings (e.g.
      "liking") and reinforcement for the two cigarette brands. Subjects were blind to
      the brand of each cigarette, and subjects abstained overnight prior to each
      session. Reinforcement was determined by responses on a computer task to earn
      single puffs on the designated cigarette. RESULTS: Subjective ratings differed
      between the low versus moderate cigarette nicotine dose under both independent
      and concurrent assessment conditions, as expected. Notably, this dose difference
      was smaller in women than in men (i.e. significant sex by dose interactions). The
      dose effect on smoke reinforcement also was smaller in women than men, but only
      under the independent and not concurrent assessment condition. CONCLUSIONS: These
      results indicate that cigarette nicotine dose is a less important influence on
      the subjective and, under some conditions, reinforcing effects of smoking in
      women than in men.

PMID- 12202967
TI  - The effect of beta-adrenergic blockade after encoding on memory of an emotional
      event.
AB  - RATIONALE: Animal and human studies lend support to the hypothesis that enhanced
      memory associated with emotional experiences involves activation of the beta
      adrenergic system. Evidence for the role of noradrenaline in emotional memory in
      humans has been gathered from experimental studies where blockade of the beta
      adrenergic system with a beta-blocker selectively impaired long-term memory for
      an emotionally arousing story (a slide show), when the beta-blocker was given
      before subjects were confronted with the emotional stimuli. OBJECTIVE: The
      purpose of this study was to test whether effective beta-adrenergic blockade
      occurring only after the stage of encoding has a similar impairing effect on
      memory. METHODS: In a double blind experimental design, 60 healthy adult subjects
      received randomly one tablet of either propranolol (Inderal, 40 mg) or placebo.
      Drugs were administered just before the slide show begun and (in view of its
      pharmacokinetics) propranolol reaches peak levels 1 h after drug intake.
      Physiological arousal was monitored by heart rate and blood pressure. Half of the
      beta-blocker and placebo groups watched either a neutral or an arousal version of
      an 11-slide presentation. Memory performance was tested with a surprise free
      recall and recognition test 1 week later. RESULTS: Memory performance,
      specifically for the second phase in which emotional elements were introduced,
      was better in subjects who viewed the arousal version than subjects who saw the
      neutral version of the slide show. However, no effect of the beta-blocker
      condition was found. CONCLUSION: This experiment does not support a role for
      noradrenaline in the post-encoding phase and on the later processes of
      consolidation and retrieval. Although it remains possible that with a different
      dosage or timing protocol a post-treatment effect of noradrenaline in humans can
      be found, this experiment could not find support for it.

PMID- 12202968
TI  - Effects of selegiline (L-deprenyl) during smoking and short-term abstinence.
AB  - RATIONALE: Changes in dopamine level are thought to play an important role in
      both smoking reward and withdrawal symptoms during abstinence. Medications that
      modulate dopamine levels may have beneficial effects on both withdrawal symptom
      levels and on response to smoking lapses during abstinence. OBJECTIVES: To
      examine the effects of the selective MAO-B inhibitor selegiline on withdrawal
      symptoms, smoking behavior and smoking satisfaction ratings. METHODS: Fifteen
      smokers received selegiline (10 mg/day) and placebo (in counterbalanced order) on
      Monday through Thursday of 2 study weeks, separated by a 2-week washout. During
      each study week, ad lib smoking sessions were scheduled to assess smoking
      behavior both before and after a brief period of abstinence. Subjective
      withdrawal symptoms and mood were measured daily, and a modified Stroop test
      sensitive to withdrawal was scheduled during the period of abstinence. RESULTS:
      Selegiline decreased craving, especially during abstinence, and impaired
      performance on the modified Stroop test during subjects' attempts to abstain.
      Medication also reduced number of cigarettes smoked and smoking satisfaction
      ratings during the smoking sessions both before and after the brief abstinence
      attempt. CONCLUSION: These results are consistent with an important role of
      dopamine in smoking behavior and abstinence. They suggest that pharmacological
      reduction of MAO-B levels during the early part of a quit attempt may aid in
      smoking cessation.

PMID- 12202969
TI  - Increased vulnerability to self-administer cocaine in mice prenatally exposed to
      cocaine.
AB  - RATIONALE: At least 40,000 infants born each year in the U.S. are estimated to
      have been exposed to crack cocaine and, therefore, may be at risk for increased
      vulnerability to cocaine addiction. OBJECTIVES: The present study tested the
      hypothesis that prenatal exposure to cocaine significantly increased subsequent
      cocaine-taking behavior in mice. METHODS: Swiss Webster male mice that had been
      exposed to cocaine in utero were tested at 5 months of age in the cocaine self
      administration paradigm. They were the offspring of dams that received one of the
      following treatments during gestation days 8-17: cocaine (40 mg/kg or 20 mg/kg
      per day; COC40 and COC20 mice, respectively), saline with access to food ad
      libitum (SAL mice), or saline with access to food restricted to that of the COC40
      dams (i.e., pair-fed; SPF40 mice). Mice were initially trained to lever press for
      a condensed-milk solution, were implanted with an indwelling intravenous (i.v.)
      catheter and, subsequently, allowed to self-administer cocaine (0.25, 0.5, 1.0,
      or 2.0 mg/kg per injection) under a fixed ratio (FR) 1 schedule of reinforcement.
      RESULTS: Latency for acquisition of food-reinforced responding appeared to be
      independent of prenatal treatment, as was acquisition of cocaine self
      administration, which was found to be dose dependent. Both COC40 and SAL mice
      reached cocaine self-administration criteria at 1.0 mg/kg or 2.0 mg/kg per
      injection doses, while neither group did so at lower doses. It was also observed
      that, at each of the doses tested, a higher number of COC40 mice reached criteria
      for acquisition. A logistic regression analysis confirmed that the likelihood for
      acquiring cocaine self-administration was positively correlated to prenatal
      exposure to cocaine and the dose of cocaine tested. CONCLUSIONS: These data
      provide evidence, for the first time, that prenatal exposure to higher doses of
      cocaine increase the probability of acquiring cocaine self-administration at
      moderate doses during adulthood and modulate vulnerability to cocaine-taking
      behavior in mice.

PMID- 12202970
TI  - Environmental stimuli promote the acquisition of nicotine self-administration in
      rats.
AB  - RATIONALE: Environmental stimuli associated with drugs of abuse are believed to
      play a major role in the motivation to take drugs, drug dependence, and relapse.
      Previous work from this laboratory demonstrated that the response-contingent
      presentation of drug-related, visual cues was at least as important as nicotine
      in the maintenance, extinction and reacquisition of self-administration in
      experienced rats. OBJECTIVES: In the present research, we asked whether these
      same visual cues are effective in promoting the acquisition of operant responding
      in drug naive rats. METHODS: Male Sprague-Dawley rats were tested for self
      administration of IV nicotine (0.03 mg/kg, free base) in 1-h daily sessions when
      infusions were or were not paired with two lighting events: a 1-s cue light,
      followed by a 1-min period during which the chamber light was turned off and
      responding was not reinforced. RESULTS: Rats tested with cues plus nicotine
      rapidly acquired self-administration and increased their lever pressing rates as
      the schedule progressed from FR1 to FR5. Without cues, the rate of nicotine self
      administration was low and no adjustments were made in response to increasing
      schedule demands. While one of the stimuli, turning off the chamber light, was
      shown to have primary reinforcing properties, its association with nicotine
      produced a synergistic enhancement of lever pressing. Acquisition of operant
      responding was also enhanced, but to a lesser extent, by a previously neutral
      compound stimulus, i.e. the nicotine-paired cue light presented with a 1-s tone.
      CONCLUSIONS: These results illustrate a powerful interaction between
      environmental stimuli and nicotine in the acquisition of operant responding and
      indicate that both intrinsically reinforcing and previously neutral cues can
      participate in this effect.

PMID- 12202971
TI  - Cocaine and SKF-82958 potentiate brain stimulation reward in Swiss-Webster mice.
AB  - RATIONALE: The dopamine D(1)-like receptor agonist SKF-82958 reportedly blocks
      reinstatement of cocaine-seeking behavior in rats and non-human primates. It is
      not known if SKF-82958 reduces drug-seeking behaviors in animals exposed
      previously to cocaine by causing reward-like effects or withdrawal-like aversive
      effects. OBJECTIVES: Intracranial self-stimulation (ICSS) studies were conducted
      to determine if SKF-82958 has reward-like or withdrawal-like effects in mice
      exposed previously to cocaine, or under the influence of cocaine at the time of
      testing. METHODS: Swiss-Webster mice with lateral hypothalamic stimulating
      electrodes were trained to self-administer rewarding brain stimulation. The mice
      were tested in a "curve-shift" variant of the ICSS procedure after
      intraperitoneal administration of cocaine alone (2.5-20 mg/kg), SKF-82958 alone
      (0.03-0.3 mg/kg), or a mixture of both drugs (SKF 0.03 mg/kg + 2.5 or 5.0 mg/kg
      cocaine). Each treatment was given twice. RESULTS: Cocaine and SKF-82958 each
      caused dose-dependent decreases in brain stimulation reward thresholds that were
      largest immediately after administration. A dose of SKF-82958 with no reward
      related effects of its own potentiated the reward-related effects of low doses of
      cocaine. Repeated administration did not cause progressive changes in the ability
      of any treatment to decrease thresholds. CONCLUSIONS: Cocaine and SKF-82958 each
      potentiate the rewarding effects of lateral hypothalamic brain stimulation in
      Swiss-Webster mice, implying that these drugs have rewarding effects of their
      own. The reward-facilitating effects of low doses of cocaine and SKF-82958 are
      additive (or synergistic). These data suggest that SKF-82958 may decrease cocaine
      seeking behavior by mechanisms related to reward rather than aversion.

PMID- 12202972
TI  - Semiautomated quantitation of carotid artery stenosis in gadolinium-bolus
      magnetic resonance angiography.
AB  - Magnetic resonance angiography (MRA) has become the standard method for
      evaluation of carotid occlusive disease. Fast imaging methods combined with bolus
      intravenous injection of gadolinium contrast have improved the quality of these
      images. Nevertheless, the gold standard for evaluation was based on projection
      arterial angiography. The properties of these images are rather different.
      Whereas most previous evaluations of MRA have used visual assessment of images,
      we evaluate an algorithm in which a computer algorithm plays the primary role in
      defining arterial lumen margins, hence, disease. The accuracy of this
      semiautomated algorithm is shown to compare favorably with gold-standard
      arteriography in a series of 50 patients.

PMID- 12202974
TI  - Development and clinical application of drug delivery systems for cancer
      treatment.

PMID- 12202973
TI  - NSAIDs in dermatologic therapy: review and preview.
AB  - BACKGROUND: Nonsteroidal anti-inflammatory drugs (NSAIDs) have been an important
      therapy in the treatment of a large number of cutaneous pathologies for more than
      three decades. OBJECTIVE: In this retrospective review, we document the use of
      NSAIDs in more than 15 common and uncommon dermatoses, including acne, psoriasis,
      sunburn, erythema nodosum, cryoglobulinemia, Sweet's syndrome, systemic
      mastocytosis, as well as urticarial, livedoid, and nodular vasculitis. NSAIDs act
      mainly by inhibiting prostaglandin synthesis by the cyclooxygenase (COX) pathway.
      CONCLUSION: Recent studies link prostaglandin to cutaneous carcinogenesis, thus
      expanding the dermatologic use of NSAIDs. They may be effective in the treatment
      and prevention of non-melanoma skin cancer, and specific COX-2 inhibitors promise
      safer, broader, long-term use of these pharmacologically innovative drugs.

PMID- 12202975
TI  - Brief review of advances in the treatment of gastric carcinoma in North America
      and Europe, 1995-2001.
AB  - Gastric carcinoma is widespread in many South American and Asian countries but
      may be especially deadly in the West, due to a lack of programs for early
      diagnosis. Advanced gastric carcinoma is incurable, and the median survival time
      of patients with advanced disease is only 6 to 9 months. We sought to examine
      investigative trends in the utilization of new agents in the treatment of
      advanced gastric carcinoma in North America and Europe. Representative published
      reports of phase II and III clinical trials of therapies for gastric carcinoma by
      investigators based in North America and Europe from January 1995 through
      December 2001 were identified by a computerized search of the PubMed literature
      database. Fluorouracil, cisplatin, leucovorin, methotrexate, doxorubicin, and
      mitomycin were considered "conventional" agents; all other drugs were considered
      "new" agents. Of the 42 reports identified by the literature search, 17 were by
      investigators in North America and 25 were by investigators in Europe. All
      reports by investigators in North America were phase II trials, compared with 64%
      of those studies in Europe; the other studies by European investigators were
      phase III trials (36%). Chemotherapeutic drugs we considered "new" for the
      purpose of this study were investigated in 64% of all trials in North America and
      Europe. Eighty-one percent (22/27) of the 27 trials in which new agents were
      studied were phase II studies. We conclude that new agents are being widely
      incorporated in the investigation of advanced gastric cancer in North America and
      Europe. This trend is likely to be continued as more new chemotherapeutic agents
      are developed for clinical testing.

PMID- 12202976
TI  - Radiofrequency thermal ablation for treatment of hepatocellular carcinoma.

PMID- 12202977
TI  - Therapeutic strategies for colorectal cancer in Europe and the United States:
      focus on chemotherapy for advanced colorectal cancer.

PMID- 12202978
TI  - Predictive molecular markers in the adjuvant therapy of breast cancer: state of
      the art in the year 2002.
AB  - In the present article, an extensive review of the current knowledge regarding
      predictive molecular markers in breast cancer is presented. The main emphasis has
      been given to the adjuvant therapy setting, because of the lack of well-designed
      studies evaluating predictive markers in the metastatic setting. In the first
      part of the article some general concepts have been summarized, mainly to
      emphasize the difference between prognostic and predictive markers. In the second
      part of the article, studies evaluating molecular markers with predictive value
      for the most commonly used drugs or regimens (i.e., cyclophosphamide,
      methotrexate, 5-fluorouracil [CMF], anthracyclines, taxanes, and herceptin) have
      been reviewed and discussed. An attempt has been made to provide for each single
      predictive marker the currently available level of evidence, to allow the reader
      to have immediate information regarding the impact of the evaluated marker in
      daily clinical practice. In the last part of the article, the most important
      findings have been summarized and future avenues of research have been outlined.

PMID- 12202979
TI  - Evidence for the use of chemotherapy in breast cancer.
AB  - Several distinct historical phases mark the evolution of chemotherapy for breast
      cancer, including the introduction of single agents in the 1960s, the development
      of cyclophosphamide, methotrexate, and 5-fluorouracil (CMF)-based regimens in the
      1970s, the evaluation of the anthracyclines in the 1980s, and the incorporation
      of the taxanes in the 1990s. The greatest benefit from the use of standard
      combination chemotherapy occurs in the adjuvant setting, where absolute
      improvements in overall survival on the order of 10% have been achieved. In
      contrast, advances have been more modest in the treatment of metastatic disease,
      and novel agents and regimens are required for further progress. Of the new
      cytotoxic drugs introduced in the past decade, the taxanes and capecitabine
      appear to be the most promising, and have demonstrated activity alone and in
      combination for the treatment of metastatic disease. The introduction of
      trastuzumab, an antibody directed against the HER2 receptor protein, heralded the
      birth of targeted molecular therapy against breast cancer. It is clear that in
      the near future the further evaluation of trastuzumab combinations and the
      development of additional molecular agents will propel clinical breast cancer
      research. One of the main challenges of the new era will be identifying and
      validating predictive factors so that therapy may be individualized based on
      tumor biology, rather than empirically selected.

PMID- 12202980
TI  - The role of aromatase inactivators in the treatment of breast cancer.
AB  - Third-generation aromatase inhibitors and inactivators have earned their place in
      the treatment of metastatic breast cancer. The third-generation aromatase
      inactivator exemestane was found to be superior to megestrol acetate as second
      line endocrine therapy in postmenopausal women, with respect to time to
      progression as well as overall survival, and the results from an ongoing study
      comparing exemestane with tamoxifen in first-line treatment are promising. The
      finding that exemestane may also work in patients previously exposed to
      nonsteroidal aromatase inhibitors reveals lack of complete cross-resistance
      between the compounds. Currently, exemestane given as monotherapy, or in sequence
      with tamoxifen (2-3 + 3-2 years of tamoxifen-exemestane or 5 years of tamoxifen
      followed by 2 years of exemestane) is being compared with tamoxifen 5 years
      monotherapy in the adjuvant setting. In addition, we are currently addressing the
      toxicity of exemestane in a placebo-controlled trial in low-risk breast-cancer
      patients. The results from these studies will outline the potential role of
      exemestane in adjuvant treatment and, potentially, for breast-cancer prevention
      in postmenopausal women.

PMID- 12202981
TI  - The challenge of palliative care.
AB  - Palliative care is patient-centered, rather than disease-focused; accepts the
      inevitability of death while simultaneously is life-affirming; addresses
      psychological, social, and spiritual concerns as well as physical ones; and is
      best delivered by a multiprofessional team working in partnership with patients
      and their families. Palliative care stresses the importance of "appropriate
      treatment" and the need for doctors not to prescribe a lingering death. Even
      though there is no chance of cure, there is much scope for psychosocial and
      spiritual healing, and often some scope for physical rehabilitation. Palliative
      care is emotionally demanding for professional carers, and strategies for
      personal support are necessary. The World Health Organization has played a major
      part in the ongoing campaign to improve cancer pain management and to make
      medicinal morphine more widely available. A systematic approach to pain and
      symptom management is essential, and there is need for specific training for all
      health professionals. In most countries, for palliative care to take root, there
      is need for a charismatic "champion". However, for palliative care to flourish,
      there is need for a governmental commitment to its development. Charisma
      continues to be necessary to prevent palliative care being strangled by an over
      rigid bureaucracy, but incorporation into existing health delivery systems is
      necessary to prevent it being stillborn through lack of resources.

PMID- 12202982
TI  - Chromosome 3p and breast cancer.
AB  - Solid tumors in humans are now believed to develop through a multistep process
      that activates oncogenes and inactivates tumor suppressor genes. Loss of
      heterozygosity at chromosomes 3p25, 3p22-24, 3p21.3, 3p21.2-21.3, 3p14.2, 3p14.3,
      and 3p12 has been reported in breast cancers. Retinoid acid receptor beta2
      (3p24), thyroid hormone receptor beta1 (3p24.3), Ras association domain family 1A
      (3p21.3), and the fragile histidine triad gene (3p14.2) have been considered as
      tumor suppressor genes (TSGs) for breast cancers. Epigenetic change may play an
      important role for the inactivation of these TSGs. Screens for promoter
      hypermethylation may be able to identify other TSGs in chromosome 3p.
      Alternatively, use of an "epigenetic modifier" may enhance the response to
      another type of agent for breast cancer.

PMID- 12202983
TI  - MYEOV, a gene at 11q13, is coamplified with CCND1, but epigenetically inactivated
      in a subset of esophageal squamous cell carcinomas.
AB  - DNA amplifications at 11q13 are frequently observed in esophageal squamous cell
      carcinoma (ESC) and correlate with a malignant phenotype. Although this amplicon
      spans a region of several megabases and harbors numerous genes, CCND1 and EMS1
      are thought to be the relevant candidates in ESC. We investigated whether the
      putative transforming gene MYEOV, mapping 360 kb centromeric to CCND1 and
      activated concomitantly with CCND1 in a subset of t(11;14)(q13;q32) positive
      multiple myeloma cell lines, represents a target of 11q13 amplification in ESC.
      To evaluate the role of MYEOV in ESC, we tested 31 ESC cell lines and 48 primary
      tumors for copy number levels of MYEOVand demonstrated that MYEOV was always
      coamplified with CCND1. However, MYEOV expression levels correlated only
      inconsistently with DNA amplification data. Treatment with the demethylating
      agent 5-aza-2'-deoxycytidine restored MYEOV expression in a subset of cell lines
      exhibiting DNA amplification without high MYEOV expression, suggesting that MYEOV
      is transcriptionally silenced by a DNA methylation mechanism in most of the
      latter cell lines. Our results indicate that MYEOV is a coamplified gene with
      CCND1 at 11q13, but its activation is sometimes inhibited by an epigenetic
      mechanism.

PMID- 12202984
TI  - Transmission of Y chromosomal microdeletions from father to son through
      intracytoplasmic sperm injection.
AB  - We conducted chromosomal analysis of three male infants fathered by severe
      oligozoospermic males with Y chromosomal microdeletions through intracytoplasmic
      sperm injection (ICSI). Two of the infants had the same Y chromosomal
      microdeletions as their fathers. The third infant also had a Y chromosomal
      microdeletion, which was longer than that found in his father. The results
      confirm that Y chromosomal microdeletions are transmitted from a father to a son
      via ICSI and also suggest that the microdeletions may be expanded during such
      transmission. Genetic counseling for infertile couples contemplating ICSI is
      important if the male carries Y chromosomal microdeletions.

PMID- 12202985
TI  - Absence of mutation in the NOD2/CARD15 gene among 483 Japanese patients with
      Crohn's disease.
AB  - Chronic inflammatory bowel diseases (IBDs), specifically Crohn's disease (CD) and
      ulcerative colitis (UC), have increased significantly in western countries and
      Japan over the last decade, but very little is known about their pathogenesis. A
      candidate-gene approach recently identified NOD2/CARD15 as one susceptibility
      gene from the IBD1 locus on chromosome 16. Alterations in this gene were found in
      many Caucasian patients with CD; in particular, two nonsynonymous substitutions
      (R702W and G908R) and a frameshift mutation (1007fs) were shown to be independent
      risk factors for CD. We investigated DNA from 483 Japanese CD patients to detect
      those three mutations in NOD2/CARD15 by appropriate genotyping techniques, but
      found only an R702Q substitution in a single patient. Direct sequencing of DNA
      from 96 of our patients in the regions containing the three reported major
      mutations detected no sequence alterations of consequence. Our findings indicate
      that the NOD2/CARD15 gene is not a major contributor to CD susceptibility in the
      Japanese population.

PMID- 12202986
TI  - A novel missense mutation (I344K) in the SPG4gene in a Korean family with
      autosomal-dominant hereditary spastic paraplegia.
AB  - Hereditary spastic paraplegia (HSP) is a group of clinically and genetically
      heterogeneous neurodegenerative disorders characterized by slowly progressive
      spasticity and weakness of the lower extremities. Among eight loci linked with
      autosomal-dominant (AD)-HSP, the SPG4 locus on chromosome 2p22 accounts for about
      40% of all patients. Recently, mutations in a new member of the AAA protein
      family, called spastin, have been identified as responsible for SPG4-linked AD
      HSP. Here, we describe a novel missense mutation (c.1031T>A; I344K) in exon 7 of
      the SPG4 gene identified in a Korean family with typical clinical features of
      pure AD-HSP. The mutation affects the third amino acid of the highly conserved
      AAA cassette domain, which is the most fore part of the domain altered by a
      missense mutation reported so far. Clinical presentations of affected individuals
      carrying the I344K mutation were not different from those of pure AD-HSP with
      SPG4 mutations reported previously. However, it is noteworthy that neither
      urinary dysfunction nor involvement of upper extremities was noticed in this
      family. To our knowledge, this is the first report of genetically confirmed AD
      HSP in Korea.

PMID- 12202987
TI  - A catalog of 106 single-nucleotide polymorphisms (SNPs) and 11 other types of
      variations in genes for transforming growth factor-beta1 (TGF-beta1) and its
      signaling pathway.
AB  - Transforming growth factor-beta1 (TGF-beta1) is a multifunctional cytokine that
      is produced in the platelet, bone, placenta, and other tissues. It acts as a
      growth inhibitor in many types of cells, and also mediates extracellular matrix
      production and immunosuppression. Mutations in the specific domain of its gene (
      TGFB1) cause Camurati-Engelmann disease, a bone-sclerosing disorder, and those in
      other domains may be associated with osteoporosis. We identified 106 single
      nucleotide polymorphisms and 11 other types of variations in TGFB1and six other
      genes. These genes were TGF-beta type I receptor gene (TGFBR1), TGF-beta type II
      receptor gene (TGFBR2), SMAD2 gene (SMAD2), SMAD3 gene (SMAD3), SMAD4 gene
      (SMAD4), and SMAD7 gene (SMAD7), all of which compose the TGF-beta1 signaling
      pathway. We also estimated allele frequencies of these DNA polymorphisms among 48
      Japanese individuals. Our data will provide a useful resource for the study of
      disease susceptibility.

PMID- 12202988
TI  - Molecular analysis of the alpha-N-acetylglucosaminidase gene in seven Japanese
      patients from six unrelated families with mucopolysaccharidosis IIIB (Sanfilippo
      type B), including two novel mutations.
AB  - Molecular analysis of the alpha-N-acetylglucosaminidase gene in seven Japanese
      patients with Sanfilippo syndrome type B from six unrelated families was carried
      out, and six disease-causing mutations were found. The parents of Patient 2 had a
      consanguinous marriage, but other families did not have any record of
      consanguinity. Two families were from Okinawa Island, where more patients with
      Sanfilippo syndrome were found than in other areas in Japan. Patients 1 and 6
      showed the most severe phenotype with rapid progression. Patients 2, 5, and 7
      were moderate. Patients 3 and 4 (sib cases) showed an attenuated form compared
      with other patients. Patients 1, 2, and 6 were homozygous for R482W, R565W, and
      R565P, respectively. Patients 3 and 4 were compound heterozygous for F314L and
      R565P. Patient 5 had delTG2171-2172 in exon 6 in one allele, and the other allele
      was unknown. Patient 7 was compound heterozygous for V241M and R482W. The family
      of Patients 3 and 4 and that of Patient 6 are unrelated, although both families
      are from Okinawa Island, and the patients have the same mutation, R565P; thus,
      R565P might be a common mutation in the Okinawa district. F314L and V241M are
      novel mutations.

PMID- 12202989
TI  - Chromosomal FISH analysis of unfertilized human oocytes and polar bodies.
AB  - The incidence of chromosomal aneuploidy was studied in 208 unfertilized metaphase
      II human oocytes from an in vitro fertilization program by fluorescence in situ
      hybridization using probes for chromosomes 18, 21, and X. Chromosome spreads were
      prepared by a gradual fixation-air-drying method. We obtained analyzable results
      from 183 oocytes and 93 polar bodies; 167 oocytes (91%) were normal, 11 (6%) were
      diploid, and 5 (3%) were aneuploid. Of the five aneuploid oocytes, four involved
      chromosome 21, and one involved the X chromosome. In this study, oocyte
      aneuploidy caused by both nondisjunction of bivalent chromosomes and predivision
      of univalent chromosomes was observed. The aneuploidy rate (9.8%) in the oocytes
      from women aged >==35 years was significantly higher than that (0.7%) in those
      aged 23 to 34 years ( P = 0.0017).

PMID- 12202990
TI  - Functional promoter polymorphism in SREBP cleavage-activating protein (SCAP).
AB  - We report the identification of a loss-of-function -11C>T promoter mutation in
      the gene encoding the sterol regulatory element binding protein cleavage
      activating protein (SCAP). The -11T allele was associated with a marked reduction
      in promoter activity in a luciferase-based expression system. We also report
      additional common single-nucleotide polymorphisms in the SCAP promoter and coding
      sequence that were identified by using direct sequencing to screen the genomic
      DNA of subjects with combined hyperlipidemia. These markers might be useful for
      studies of association with metabolic phenotypes.

PMID- 12202991
TI  - A novel splice variant of the cell adhesion molecule contactin 4 ( CNTN4) is
      mainly expressed in human brain.
AB  - Axon-associated cell adhesion molecules (AxCAMs) of the immunoglobulin
      superfamily play important roles in the formation, maintenance, and plasticity of
      functional neuronal networks. Contactin4 ( CNTN4, BIG-2) is a member of the TAG
      1/F3 subgroup of AxCAMs. We have cloned a novel splice variant of CNTN4, and term
      it CNTN4A. The complete nucleotide sequence of CNTN4 is also obtained by
      combining the insert sequences of two clones, which were isolated when screening
      the human fetal brain cDNA library with CNTN4A as a probe. CNTN4A protein has an
      N-terminal cleavable signal peptide, two FNIII-like domains, and a glycosyl
      phosphatidylinositol-anchoring domain. According to the search of the human
      genome database, CNTN4 was mapped to 3p25-26, a region very close to the
      breakpoints of the 3p syndrome. Expression analysis of CNTN4A shows that CNTN4A
      is mainly expressed in brain.

PMID- 12202992
TI  - SNP genotyping in the beta(2)-adrenergic receptor by electronic microchip assay,
      DHPLC, and direct sequencing.
AB  - The beta(2)-adrenergic receptor (beta2AR) is the key target for the beta(2)
      agonist drugs used for bronchodilation in asthma and chronic obstructive
      pulmonary disease. To detect four SNPs with amino acid variations at positions 
      47T/C (CysBUP19Arg), 46A/G (Gly16Arg), 79C/G (Gln27Glu), and 491C/T (Thr164Ile)
      in the beta 2AR gene, we used the electronic microchip assay, denaturing high
      performance liquid chromatography (DHPLC), and direct sequencing. Genomic DNA
      samples were obtained from the blood of 84 Japanese healthy volunteers. The
      agreement rates of the first data set with the final data (allele calls) were
      99.7% (332/333), 99.2% (246/248), and 96.7% (329/340). The percentages of no
      allele designation (ND) were 2.06% (7/340), 2.75% (7/255), and 0.00% (0/340) for
      the electronic microchip assay, DHPLC, and direct sequencing, respectively.
      Furthermore, we found three samples that had a novel haplotype.

PMID- 12202993
TI  - Tuberous sclerosis in a 19-week fetus: immunohistochemical and molecular study of
      hamartin and tuberin.
AB  - Tuberous sclerosis complex (TSC) is a genetically heterogeneous disease caused by
      mutations of TSC1 or TSC2 genes. It involves multiple organ systems resulting in
      mild to lethal hamartoma formation due to gene mutation in the germ line and loss
      of heterozygosity (LOH) in somatic cells. Hamartin (TSC1) and tuberin (TSC2) are
      expressed broadly. However, little is known about tissue susceptibility to
      hamartomas when equal or similar amounts of TSC gene expression are present. In
      this study, we present a 19-week gestational age fetus with pathological features
      of TSC, which was confirmed by finding LOH of TSC2 in a cardiac rhabdomyoma.
      Developmental expression of hamartin and tuberin in the TSC fetus, an age-matched
      non-TSC fetus, and a 26-week gestational age non-TSC fetus were analyzed by
      immunohistochemistry. We found that in addition to the differential expression of
      the TSC genes in some normal tissues compared with that in the TSC-affected
      fetus, the cellular localization and distribution of hamartin and tuberin were
      dramatically different in different tissues. In general, hamartin and tuberin are
      mainly expressed in epithelial cells, myocytes, and neural tissues. By comparing
      the incidence of the hamartomas in early childhood and gene expression in
      tissues, it appears that tissues with co-expression of hamartin and tuberin are
      prone to a higher incidence of hamartomas than those expressing only one protein,
      or two proteins but in different patterns of cellular localization.

PMID- 12202994
TI  - Significance of p53 expression in immature teratomas.
AB  - Twenty-nine pediatric immature teratomas were reviewed to determine the frequency
      and clinical significance of p53 expression. Tumors were stained for p53
      expression by immunohistochemistry and results were correlated with the presence
      of other germ cell tumor elements and with outcome. Sequencing of p53 for
      mutations was performed on positive cases. Eighteen cases showed widespread
      positive p53 staining of the immature teratoma elements, 9 showed staining only
      in very occasional cells, and 2 cases showed no staining. Of the 18 positive
      cases, 5 recurred. All five were pure immature teratomas at diagnosis. Four
      recurred as immature or mature teratoma and one as a sarcoma; all except one
      showed frequent cells positive for p53 in the recurrent tumor. Another 5 of the
      18 diffusely positive cases contained immature teratoma as well as other
      malignant germ cell elements at diagnosis; none of these recurred. None of the
      remaining eight cases with frequent positive cells, the nine cases with
      occasionally positive p53 staining, or the two cases with no staining recurred or
      demonstrated other germ cell tumor elements. We conclude that p53 expression is
      not unusual in immature teratoma and diffuse p53 immunopositivity is associated
      with recurrence or the presence of malignant elements in approximately 50% of
      cases. In only 1 of 29 cases tested was p53 immunopositivity associated with
      mutations in the p53 gene; hence, overexpression in the majority of cases is
      presumed to reflect increased half-life of the protein from undetermined
      stabilizing factors. Expression of p21, a p53 target gene, was only focal,
      suggesting impaired transcriptional activation by p53. The finding of frequent
      p53-positive cells in immature teratoma should prompt a search for malignant
      elements within the tumor and affected patients should be followed closely for
      evidence of recurrence.

PMID- 12202995
TI  - Central nervous system embryogenesis and its failures.
AB  - The well-orchestrated development of the central nervous system (CNS) requires
      highly integrated regulatory processes to ensure its precise spatial organization
      that provides the foundation for proper function. As emphasized in this review,
      the type, timing, and location of regulatory molecules influence the different
      stages of development from neuronal induction, regional specification, neuronal
      specification, and neuronal migration to axonal growth and guidance, neuronal
      survival, and synapse formation. The known molecular mechanisms are summarized
      from studies of invertebrates and lower vertebrates, in which we have learned
      more about the different ligands, receptors, transcription factors, and the
      intracellular signaling pathways that play specific roles in the different stages
      of development. Despite known molecular mechanisms of some disturbances, most of
      the clinical entities that arise from failures of CNS embryogenesis remain
      unexplained. As more novel genes and their functions are discovered, existing
      mechanisms will be refined and tenable explanations will be made. With these
      limitations, two specific clinical entities that have been relatively well
      studied, holoprosencephaly and neuronal migration defects, are discussed in more
      detail to illustrate the complexity of regulatory mechanisms that govern well
      defined stages of CNS development.

PMID- 12202996
TI  - Value of the perinatal autopsy: critique.
AB  - In consenting to a perinatal autopsy, the primary motive of parents may be to
      find the exact cause of death. A critical review on the value of perinatal
      autopsies was performed to see whether parents could be counseled regarding their
      main motive. A literature search was performed in MEDLINE, EXCERPTA MEDICA, and
      the Cochrane library. We evaluated the value of the autopsy by comparing the
      clinical and autopsy diagnoses in stillbirths, neonatal deaths, and therapeutic
      terminations. Clinicopathologic concordance was divided into four categories: (1)
      change in diagnosis, (2) additional findings, (3) complete confirmation, and (4)
      inconclusive. We sought information on factors that may influence the value of
      perinatal autopsies: the type and definitions of perinatal loss; autopsy rate;
      level of hospital; expertise of pathologists; autopsy protocol used; whether
      patients were inborn or referred; and antenatal diagnosis. From the 27 articles
      that met our review criteria, the autopsy revealed a change in diagnosis or
      additional findings in 22% to 76% of cases. If confirmation of clinical findings
      is included, then the value of the perinatal autopsy was as high as up to 100%.
      Factors that could influence this rate were reported variably by investigators.
      When centers report their experience of the value of the perinatal autopsy,
      information on the factors that may influence their reports should be provided as
      well. Clinicians can confidently advise parents of the usefulness of the
      perinatal autopsy in ascertaining the cause of death or for counseling their
      future pregnancies.

PMID- 12202997
TI  - Triplet placentas: reference values for weights.
AB  - The occurrence of twins, triplets, and other multiple births increased
      significantly between 1970 and 2000 in the United States and other industrialized
      countries. The number of triplet placentas submitted for examination as
      pathologic specimens has also markedly increased, but no reference values are
      published for triplet weights. We examined 196 normal triplet placentas.
      Specimens with associated conditions known to affect the weights of the placentas
      were excluded. The gestational ages ranged between 20 and 38 weeks. Mean weights
      for different gestational ages are summarized as follows: 253 g for 20 weeks, 319
      g for 22 weeks, 406 g for 24 weeks, 509 g for 26 weeks, 621 g for 28 weeks, 738 g
      for 30 weeks, 855 g for 32 weeks, 965 g for 34 weeks, 1,065 g for 36 weeks, and
      1,147 g for 38 weeks. Weight gain of triplet placentas appears to parallel that
      of twin placentas. The mean values of placental weights for triplets at each
      gestational age are less than triple those of singleton weights for the same
      duration of gestation. The placental weights in multiple gestations do not
      increase proportionately with the number of fetuses.

PMID- 12202998
TI  - Expression of apoptosis-related antigens, Fas, bcl-2, and p53, and Mib-1
      proliferation index in the hypoplastic thymus of DiGeorge syndrome.
AB  - Apoptosis, along with cellular proliferation, plays a major role in normal
      developmental processes and tissue homeostasis. We hypothesized that altered
      apoptosis-related pathways and/or reduced cell proliferation might play a role in
      the thymic hypoplasia or aplasia in DiGeorge syndrome (DG). We used
      immunohistochemistry to evaluate the apoptosis-related antigens Fas (CD95), bcl
      2, and p53, as well as Mib-1 proliferation index in the thymuses from six
      patients with DG. The results were compared with those from the thymuses from six
      patients with non-DG congenital heart disease. All DG patients (age 32 weeks GA
      to 4 months) had hypoplastic thymuses ranging from microscopic foci to 2.7 g in
      weight (expected for age, 4.7 +/- 3.6 g to 10 +/- 6 g). The thymic weights from
      the patients with non-DG congenital heart disease (age 37 weeks GA to 1 month)
      ranged from 3 to 5.6 g and were at the lower range of expected weight by age
      (expected for age, 8.4 +/- 5.6 g to 12 +/- 7 g). All thymuses showed histologic
      features of stress-induced involution. In both groups, a - 50% Mib-1
      proliferation index was found in the cortical thymocytes, whereas <5% Mib-1
      labeling was seen in the medullary thymocytes; Fas stained medullary epithelial
      cells (3+) and cortical epithelial cells (1+); bcl-2 stained medullary thymocytes
      (3+) and cortical thymocytes (1+); p53 stained less than 1% of nuclei in all
      sections. No significantly altered Mib-1 proliferation index or expression of
      Fas, bcl-2, and p53 was observed in the hypoplastic thymuses in DG, compared to
      these same measures in non-DG. These results suggest that thymic hypoplasia in DG
      may be mediated by mechanisms other than reduced cellular proliferation and/or
      altered Fas, bcl-2, and p53 apoptotic pathways.

PMID- 12203000
TI  - Presentation, diagnosis, and management of arterial mycotic pseudoaneurysms in
      injection drug users.
AB  - Injection drug users frequently present with abscess, cellulitis, and
      endocarditis. The development of arterial mycotic pseudoaneurysm (AMP) as a
      sequela of injection drug use, however, is much less frequently reported. We
      undertook a study to determine the prevalence and presenting clinical
      characteristics of AMP, utilizing a retrospective review of all emergency
      department cases seen at one city public hospital for the 5-year period 1994
      1999. Initial evaluation included physical examination, CT scan, ultrasound,
      and/or angiography. There were 7,795 patient visits for complications of
      injection drug use; 11 patients had AMP (0.14%). AMP involved the brachial (n =
      5), subclavian (n = 2), radial (n = 2), femoral (n = 1) and popliteal arteries (n
      = 1). Fever was absent in the majority of patients (7/11). Either pulsatility or
      a mass was noted in three cases, and both were seen in 6/11 (54%). AMP was not
      initially suspected in three cases, which were treated as abscesses and
      surgically incised, resulting in arterial rupture. The annual prevalence of AMP
      in the presenting population was estimated to be 0.03%. However, a high index of
      suspicion for AMP should be maintained with injection drug users presenting with
      a mass or pulsatility over an artery, as there is risk of rupture, rapid
      exsanguination, and distal embolization.

PMID- 12203001
TI  - Renal artery to inferior vena cava fistula following gunshot wound to the
      abdomen.
AB  - Traumatic fistula involving the renal artery and IVC is a rare event, and
      typically is a result of penetrating injury. A case of right renal artery to IVC
      fistula following a gunshot wound to the abdomen is reported, and illustrates the
      significant hemodynamic changes that accompany these fistulae. We also emphasize
      the importance of thorough initial exploration of retroperitoneal hematomas
      following penetrating trauma, and review management options in the treatment of
      renal arteriovenous fistulae.

PMID- 12203002
TI  - Transition to all-autogenous hemodialysis access: the role of preoperative vein
      mapping.
AB  - Safe, reliable, and efficient hemodialysis access (DA) remains an unrealized
      ideal. Autogenous dialysis access (ADA) may improve outcome for renal failure
      patients. We now place ADA in 9 out of 10 new patients in an effort to maximize
      primary patency and minimize access-related complications. We reviewed our recent
      DA experience to determine whether our increased reliance on autogenous access
      (ADA) has improved outcomes, and to evaluate the impact of preoperative duplex
      venous imaging (vein mapping) on early and intermediate results. We conducted a
      retrospective database review of 108 consecutive patients undergoing initial
      permanent DA between 10/97 and 8/01. Mean follow-up was 13.1 months. Our results
      showed that increased ADA utilization decreases the need for secondary access
      procedures. The functional superiority of ADA vs. prosthetic dialysis access
      (PDA) in this series may be due to optimal autogenous conduit selection
      facilitated by preoperative vein mapping.

PMID- 12203003
TI  - A CUSUM analysis of ruptured abdominal aortic aneurysm repair.
AB  - Studies have investigated the role of hospital and surgeon case volume in outcome
      after ruptured abdominal aortic aneurysm repair (rAAA). Few have analyzed the
      learning curve of an individual surgeon. The purpose of this study was to analyze
      this learning curve in reducing morbidity and mortality after rAAA repair. Thirty
      two consecutive patients who underwent rAAA repair during the initial 2.5 years
      of a vascular surgeon's career were reviewed retrospectively. They were divided
      temporally into two groups of 16 patients (groups 1 and 2). Outcome measures
      included mortality, postoperative myocardial infarction, stroke, and renal and
      respiratory failure. Perioperative variables previously associated with increased
      mortality were analyzed. The cumulative sum (CUSUM) method was used to analyze
      the learning curve with respect to published acceptable event rates and
      predetermined 80% alert and 95% alarm boundary lines. Groups 1 and 2 did not
      differ statistically in age, preoperative blood pressure, hemoglobin or
      creatinine. There was no difference in transfusion requirements (6.8 +/- 1.2
      units vs. 6.4 +/- 1.0 units; p = 0.78), urine output (340 +/- 65 mL vs. 389 +/-
      94 mL; p = 0.72) or clamp position. There was no difference in the incidence of
      postoperative myocardial infarction, stroke, or respiratory or renal failure.
      Thirty-day mortality in group 2 was 12% as compared to 50% in Group 1 (p = 0.03).
      On CUSUM analysis, the cumulative failure rate in group 2 progressed lower than
      the 80% reassurance line, indicating improved results with time. Mortality after
      rAAA repair decreased over time during an early period of an individual surgeon's
      career. The CUSUM method is a valuable tool in analyzing an individual surgeon's
      experience and shows promise in quality control in vascular surgery.

PMID- 12203004
TI  - Does ASA classification impact success rates of endovascular aneurysm repairs?
AB  - The purpose of this study was to evaluate the technical success, clinical
      success, postoperative complication rate, need for a secondary procedure, and
      mortality rate with endovascular aneurysm repair (EAR), based on the physical
      status classification scheme advocated by the American Society of
      Anesthesiologists (ASA). At a single institution 167 patients underwent attempted
      EAR. Query of a prospectively maintained database supplemented with a
      retrospective review of medical records was used to gather statistics pertaining
      to patient demographics and outcome. In patients selected for EAR on the basis of
      acceptable anatomy, technical and clinical success rates were not significantly
      different among the different ASA classifications. Importantly, postoperative
      complication and 30-day mortality rates do not appear to significantly differ
      among the different ASA classifications in this patient population.

PMID- 12203005
TI  - Metal ions in the structure and function of RNA.
AB  - It is becoming increasingly clear that RNA is more than a passive carrier of
      genetic information. Folded RNA molecules play key roles in almost every aspect
      of cellular metabolism, including protein transport, RNA splicing, peptide bond
      formation, and translational regulation. This is facilitated by the
      multifunctional nature of RNA biopolymers which can serve as rigid structural
      scaffolds, conformational switches, and catalysts for chemical reactions. In all
      cases, metal ions play a crucial role in RNA function. For folded RNA molecules,
      the pathway for adopting proper tertiary structure, and the stabilization of that
      structure, depends on specific and nonspecific interactions with certain classes
      of metal ions. There is a rapidly expanding repertoire of RNA structural motifs
      that typically sequester metal ions, and these are being studied using new
      spectroscopic and chemical methodologies. Many ribozymes (catalytic RNA
      molecules) depend on metal ions as cofactors that are explicitly involved in the
      chemical mechanism of catalysis. All of these functions are exemplified by recent
      studies of group II introns, which are among the largest ribozymes found in
      Nature. In this case, there are specific roles for metal ions in the folding
      pathway, the tertiary structure and the chemical mechanism.

PMID- 12203006
TI  - Dynamics of wild-type HiPIPs: a Cys77Ser mutant and a partially unfolded HiPIP.
AB  - The temperature dependence of the mean square displacement of the (57)Fe nuclei
      due to motion faster than 100 ns are measured by temperature-dependent Mossbauer
      spectroscopy for oxidized and reduced HiPIPs from Ectothiorhodospira halophila,
      Chromatium vinosum WT and a Cys77Ser mutant. The behaviour is interpretable in
      the frame of the general model of protein dynamics distinguishing two temperature
      intervals. The character of harmonic and quasi-diffusional modes in HiPIPs is
      discussed. Dynamic information obtained from Mossbauer spectroscopy and Fe K-edge
      EXAFS are compared. Structure dynamics of the iron-sulfur cluster in the
      partially unfolded reduced HiPIP from C. vinosum was investigated by Mossbauer
      spectroscopy and EXAFS, indicating an intact metal centre and a protein backbone
      with a largely collapsed secondary structure. The role of the cofactor during
      protein folding is discussed. Differences in the dynamics between the native
      protein and the molten globule are found at physiological temperatures only. The
      structure and dynamic behaviour of the [Fe(4)S(4)]Cys(3)Ser cluster in the
      Cys77Ser mutant of the HiPIP from C. vinosum are analysed. The temperature
      dependence of electron relaxation in oxidized HiPIPs is investigated by Mossbauer
      spectroscopy and analysed theoretically, considering spin-spin and spin-lattice
      relaxation. The latter consists of contributions from direct phonon bottleneck
      and Orbach mechanisms. The data agree with former pulsed EPR results. Orbach
      relaxation is interpreted as due to transitions between electronic isomers of
      oxidized HiPIPs. With this interpretation, the energetic difference between both
      isomers equals the energy gap estimated from the temperature dependence of the
      Orbach relaxation.

PMID- 12203007
TI  - Structural determinants and hydrogen-bond network of the mononuclear zinc(II)
      beta-lactamase active site.
AB  - Zinc(II)-beta-lactamases are among the latest generation of antibiotic-resistant
      enzymes developed by bacteria against beta-lactams. Here we have used density
      functional theory to provide the full structure of the catalytic site from
      Bacillus cereus mononuclear beta-lactamase II. Calculations are carried out on
      relative large models built on the X-ray structure of the free enzyme at the
      highest available resolution (1.7 A, PDB entry 3BC2). The most stable
      conformation emerging from our calculations consists of a Zn(II)-bound hydroxide,
      which acts as nucleophilic agent in the enzymatic reaction, highly stabilized by
      a complex hydrogen-bond network, in which the protonation state of Asp90 plays a
      major role. The pattern differs from that previously proposed on the basis of
      smaller models. Furthermore, the calculations confirm that Arg91 contributes to
      determine the orientation and the protonation state of Asp90, as recently
      suggested by mutagenesis experiments.

PMID- 12203008
TI  - Structure of the (113)Cd(3)beta domains from Homarus americanus metallothionein
      1: hydrogen bonding and solvent accessibility of sulfur atoms.
AB  - The three-dimensional structures of the isolated Cd(3)beta domains from Homarus
      americanus metallothionein have been determined by NMR methods in order to
      establish a set of beta-domain structures for comparative analysis. First, it was
      determined that the Cd-cysteine connectivities forming the Cd(3)S(9) metal center
      were identical to those observed for the beta(N) domain in the native
      holoprotein. Time- and temperature-dependence studies of the (113)Cd and (1)H 1D
      NMR spectra indicated that the beta(N) domain undergoes slow conformational
      changes before reaching an equilibrium structure. In addition to structural
      information provided by the metal-to-cysteine connectivities, Phi, chi(1) and
      chi(2) angle constraints, three H(N...)S hydrogen bond interactions were also
      determined from a long-range optimized (1)H(N)-(113)Cd HMQC experiment. A
      simulated annealing protocol was applied to the distance and angle constraints
      obtained from the 2D-NMR experiments to calculate the three-dimensional structure
      of the synthetic Cd(3)beta(N) domain of lobster metallothionein. Structure
      reactivity relationships are proposed for the reactions of Cd(3)beta domains with
      5,5'-dithiobis(2-nitrobenzoate), based on comparisons of surface exposure of
      sulfur atoms of the lobster and rabbit Cd(3)beta domain structures. Finally, the
      surface exposure of the beta domains of lobster is compared with beta domains
      from mammalian metallothioneins.

PMID- 12203009
TI  - Biophysical analysis of natural, double-helical DNA modified by a dinuclear
      platinum(II) organometallic compound in a cell-free medium.
AB  - Modifications of natural DNA by the dinuclear platinum(II) organometallic complex
      [[Pt(Me)Cl(Me(2)SO)](2)(mu-N-N)] [where N-N=H(2)N(CH(2))(6)NH(2)] (ORGANObisPt)
      were studied by methods of molecular biophysics. These methods include DNA
      binding studies using atomic absorption spectrophotometry, HPLC analysis of
      enzymatically digested DNA, interstrand cross-linking employing gel
      electrophoresis under denaturing conditions, DNA unwinding studied by gel
      electrophoresis, mapping of DNA adducts by transcription assay, DNA melting
      curves measured by absorption spectrophotometry and conformational analysis of
      platinated DNA by differential pulse polarography. The results indicate that the
      complex ORGANObisPt binds irreversibly to DNA. Its DNA binding mode is, however,
      different from that of the formally equivalent [[cis-PtCl(NH(3))(2)](2)(mu-N-N)]
      (1,1/c,c), which exhibits antitumor activity including that in the tumor cells
      resistant to cisplatin. Interestingly, ORGANObisPt binds to DNA considerably
      faster than 1,1/c,c and cisplatin. In addition, when ORGANObisPt binds to DNA it
      exhibits a strong base sequence specificity to guanine residues. ORGANObisPt
      forms mainly monofunctional adducts on double-helical DNA. It forms also a small
      amount of DNA interstrand cross-links (approximately 2%), i.e. a radically
      smaller amount in comparison with the complex 1,1/c,c. Importantly, these
      interstrand cross-links of ORGANObisPt are capable of terminating RNA synthesis
      in vitro, while its major monofunctional adducts are not. In addition, the
      adducts of ORGANObisPt affect the conformation of DNA, but in a different way
      than its dinuclear analogue 1,1/c,c or cisplatin. Some structural features of
      ORGANObisPt, such as the charge or nature of the trans and cis activating groups
      relative to the labile chloride, might be responsible for the altered DNA binding
      mode and biological activity in comparison with the 1,1/c,c compound.

PMID- 12203010
TI  - FeMo cofactor of nitrogenase: energetics and local interactions in the protein
      environment.
AB  - A combined broken-symmetry density functional and continuum electrostatics
      approach has been applied to the iron-molybdenum center (FeMoco) of nitrogenase
      to evaluate the energetic effects of the local amino acid environment for several
      spin alignments of FeMoco. The protein environment preferentially stabilizes
      certain spin coupling patterns. The lowest energy spin alignment pattern in the
      protein displays calculated properties that match the experimental data better
      than any of the alternative possibilities. The total interaction energy of the
      protein with FeMoco has been evaluated and the contribution of each amino acid
      residue has been broken down into sidechain and backbone components. Arginine,
      lysine, aspartate and glutamate sidechains exert the largest electrostatic
      influence on FeMoco; specific residues are highlighted and their interaction with
      FeMoco discussed in the context of the available X-ray data from Azotobacter
      vinelandii (Av). Observed data for the M(N)(resting state)-->M(OX)(one-electron
      oxidized state) and M(N)-->M(R)(one-electron reduced state) or M(I)(alternative
      one-electron reduced state) redox couples are compared with those calculated for
      Av. The calculated redox potentials are fairly insensitive to the spin state of
      the oxidized or reduced states and the predicted qualitative trend of a more
      negative redox potential for the more reduced M(N)-->M(R) or M(I) couple is in
      accord with the available redox data. These calculations represent a first step
      towards the development of a microscopic model of electron and proton transfer
      events at the nitrogenase active site.

PMID- 12203011
TI  - Effect of neurotoxic metal ions on the proteolytic activities of the 20S
      proteasome from bovine brain.
AB  - The effect of oxidative stress induced by neurotoxic metal ions on the properties
      of the brain 20S proteasome or multicatalytic proteinase complex (MPC) has been
      studied. Exposure of the 20S proteasome to increasing amounts of Fe(III), Fe(II),
      Cu(II) or Zn(II) affects its main hydrolytic activities: trypsin-like (T-L),
      chymotrypsin-like (ChT-L), peptidylglutamyl-peptide hydrolase (PGPH), branched
      chain amino acid preferring (BrAAP) and caseinolytic activities, although in
      different ways. T-L activity showed gradual activation by both iron ions but
      inhibition by Cu(II) and Zn(II). ChT-L and PGPH activities were inhibited whereas
      BrAAP activity was widely activated by all the tested metal salts except for zinc
      ions. Moreover, the exposure to ferrous salt increased the degradation rate of
      casein. The functional effects appear to be linked to oxidation-induced
      modifications, as demonstrated by an increase of carbonyl groups following the
      exposure to metal ions. In addition, modifications induced by ferrous salt on the
      catalytic subunits were also supported by western blot analyses performed using
      anti-X, anti-Y and anti-Z antibodies. The results obtained clearly indicate that
      metal-catalyzed oxidation strongly affects the functions of the brain 20S
      proteasome, even though the catalytic subunits seem to be differently influenced
      by oxidative phenomena.

PMID- 12203013
TI  - Interaction between a DNA oligonucleotide and a dinuclear iron(II) supramolecular
      cylinder; an NMR and molecular dynamics study.
AB  - A tetracationic supramolecular cylinder, [Fe(2)L(3)](4+) (L=C(25)H(20)N(4)), with
      a triple-helical architecture, is just the right size to fit into the major
      groove of DNA but too big to fit into the minor groove. A detailed NMR
      spectroscopic analysis supported by molecular dynamics (MD) calculations shows
      unambiguously the close fit between the cylinder and a duplex oligonucleotide,
      [d(GACGGCCGTC)(2)]. Furthermore, only the left-handed enantiomer of the cylinder
      seems to fit the groove geometry. With both free and complexed species of
      [Fe(2)L(3)](4+) and DNA in solution, the NMR spectra are too complicated for a
      detailed structure determination. Based on differences in chemical shifts and
      extensive MD calculations, a realistic qualitative picture of the DNA-cylinder
      adduct is presented. Several sets of chemical shifts assigned to the protons of
      the three ligand strands in the cylinder indicate that the iron complex situated
      in the major groove exhibits restricted rotation on the NMR timescale around the
      cylindrical axis. The NMR NOE data support a model where the cylinder undergoes
      both a translational and rotational oscillation in the major groove. The results
      of an NOE restrained MD calculation indicates that the cylinder induces a 40
      degrees bend of the double helix, in accordance with linear dichroism
      measurements. Other distinct features to be noticed are the very low value of the
      helical twist (16 degrees) induced at the G(4)C(5) step.

PMID- 12203012
TI  - From monomers to micelles: investigation of the parameters influencing proton
      relaxivity.
AB  - 17O NMR and (1)H NMRD studies have been performed on a series of Gd(III) 1,4,7,10
      tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) derivatives as potential
      liver-specific magnetic resonance imaging (MRI) contrast agents. They bear
      aliphatic side chains which make them capable of micellar self-organization. The
      compounds differ in the length (C10-C18) and in the chemical nature (alkyl or
      monoamide-alkyl) of their lipophilic chain. We have established a convenient
      method to determine the critical micellar concentration (cmc) of paramagnetic
      surfactants by (1)H relaxivity measurements. This technique can be easily used
      over a large temperature range; thus, it can find wide application outside the
      field of MRI contrast agents. The knowledge of the cmc allowed us to determine
      the parameters governing the water proton relaxivity of the Gd(III) chelates in
      both nonaggregated and aggregated micellar forms. The relaxation data of the
      micellar complexes have been interpreted with the Lipari-Szabo approach. This
      model allows a local motion to be separated from the global tumbling of the whole
      micelle (modulated by a local, tau(l), and a global, tau(g), rotational
      correlation time, respectively). The aggregation substantially affects the
      rotational dynamics and thus increases the proton relaxivity of the Gd(III)
      chelates. The global rotational correlation times increase with increasing length
      of the side chain (500-2800 ps for C10-C18). Local motions are also influenced by
      the length and by the hydrophobicity of the side chain. The analysis of the
      relaxation data reveals considerable flexibility for these micellar aggregates.
      The rate of water exchange obtained for these chelates is identical to that for
      [Gd(DOTA)(H(2)O)](-) (k(ex)(298)= 4.8 x 10(6)s(-1))and is not sensitive either to
      micellization or to differences in the aliphatic chain. A relaxivity gain in such
      systems could be attained by simultaneously optimizing the water exchange by
      modifications of the chelate and increasing the micelle rigidity by using water
      soluble surfactants with more hydrophobic side chains.

PMID- 12203014
TI  - Removal of a cysteine ligand from rubredoxin: assembly of Fe(2)S(2) and Fe(S
      Cys)(3)(OH) centres.
AB  - The electron transfer protein rubredoxin from Clostridium pasteurianum contains
      an Fe(S-Cys)(4) active site. Mutant proteins C9G, C9A, C42G and C42A, in which
      cysteine ligands are replaced by non-ligating Gly or Ala residues, have been
      expressed in Escherichia coli. The C42A protein expresses with a Fe(III)(2)S(2)
      cluster in place. In contrast, the other proteins are isolated in colourless
      forms, although a Fe(III)(2)S(2) cluster may be assembled in the C42G protein via
      incubation with Fe(III)and sulfide. The four mutant proteins were isolated as
      stable mononuclear Hg(II)forms which were converted to unstable mononuclear
      Fe(III)preparations that contain both holo and apo protein. The Fe(III)systems
      were characterized by metal analysis and mass spectrometry and by electronic,
      electron paramagnetic resonance, X-ray absorption and resonance Raman
      spectroscopies. The dominant Fe(III) form in the C9A preparation is a Fe(S
      Cys)(3)(OH) centre, similar to that observed previously in the C6S mutant
      protein. Related centres are present in the proteins NifU and IscU responsible
      for assembly and repair of iron-sulfur clusters in both prokaryotic and
      eukaryotic cells. In addition to Fe(S-Cys)(3)(OH) centres, the C9G, C42G and C42A
      preparations contain a second four-coordinate Fe(III)form in which a ligand
      appears to be supplied by the protein chain.

PMID- 12203015
TI  - Ultrastructural damage in chromium picolinate-treated cells: a TEM study.
      Transmission electron microscopy.
AB  - Chromium picolinate (CrPic) is a human dietary supplement that provides a
      bioavailable form of chromium(III). Its mechanism of action is unknown, and a
      number of toxic endpoints have been attributed to its use. Understanding the
      cellular effects of CrPic is important for confirmation or dismissal of these
      potential toxic effects. The purpose of this work was to characterize
      morphological damage caused by CrPic, picolinic acid, and chromic chloride in
      Chinese hamster ovary AA8 cells. A 48-h exposure to 80 micro g/cm(2) CrPic (0.44
      mg/mL CrPic) produced 45% survival by colony formation. Transmission electron
      microscopy (TEM) showed 83% of analyzed cells having swollen mitochondria with
      degraded cristae. Apoptosis was identified by nuclear convolution and
      fragmentation, and cytoplasmic blebbing. Apoptosis was quantified by fluorescence
      microscopy with acridine orange/ethidium bromide staining. At the 80 micro
      g/cm(2) dose of CrPic, 37% of the cells were apoptotic cells at 48 h. An
      equivalent dose of picolinate, 3 mM, was much more cytotoxic and thus there was
      an inadequate cell number for TEM analysis. However, a lower dose of 1.5 mM
      induced 49% cell survival, and damaged 86% of the mitochondria, with 51% of the
      cells undergoing apoptosis. A dose of 1 mM chromic chloride produced 71% cell
      survival, and damaged 86% of the mitochondria, with 22% of the cells undergoing
      apoptosis. The amount of apoptosis correlated with overall cell survival by
      colony formation, but not with the amount of mitochondrial damage. The
      coordination of Cr(III) by picolinate ligands may alter the cellular chemistry of
      Cr(III) to make chromium picolinate a toxic form of Cr(III).

PMID- 12203016
TI  - Density functional and electrostatics study of oxidized and reduced
      ribonucleotide reductase; comparisons with methane monooxygenase.
AB  - A combined broken symmetry density functional and electrostatics approach has
      been used to examine the active sites of the resting (RNR(ox)) and reduced
      (RNR(red)) forms of class I type ribonucleotide reductase in the protein and
      solvent environment. Active site cluster geometries and Heisenberg J values are
      discussed in the context of the available protein data. The total electrostatic
      interaction energy in the protein comprises a large reaction field component and
      a much smaller protein field term, the former suggesting strong dielectric
      polarization between the cluster and protein-solvent dielectrics; the latter is
      indicative of a very weak link to the protein environment. Decomposition of the
      protein field term elucidates the major electrostatic interactions between amino
      acid residues in the RNR R2 local environment and the active site cluster,
      enabling an energetic comparison of structurally equivalent residues with a
      related diiron protein, methane monooxygenase.

PMID- 12203017
TI  - Carbon monoxide dehydrogenase from Rhodospirillum rubrum produces formate.
AB  - Carbon monoxide dehydrogenase (CODH) from Rhodospirillum rubrum reversibly
      catalyzes the oxidation of CO to CO(2) at the active site C-cluster. In this
      article, the reduction of CO(2) to formate is reported as a slow side reaction
      catalyzed by both Ni-containing CODH and Ni-deficient CODH. Recently, the
      structures of R. rubrum CODH and its active site NiFeS cluster (the C-cluster)
      have been solved. The data in this manuscript describe the formate-producing
      capability of CODH with or without Ni in the active site.

PMID- 12203018
TI  - Structure-function relationship in type II cytochrome c(3) from Desulfovibrio
      africanus: a novel function in a familiar heme core.
AB  - NMR and visible spectroscopy were used to characterize the type II tetraheme
      cytochrome c(3) isolated from the periplasmic space of Desulfovibrio africanus, a
      sulfate-reducing bacterium. Although structurally similar to other cytochromes
      c(3), this protein displays distinct functional properties. Proton NMR signals
      from the four hemes were assigned to the structure in the ferri- and
      ferrocytochromes using two-dimensional NMR experiments. The thermodynamic
      parameters of the hemes and of an acid-base center in the type II cytochrome c(3)
      were determined using NMR and visible spectroscopies. The thermodynamic features
      indicate that electrostatic effects dominate all of the interactions between the
      centers and no positive cooperativity between hemes is observed. The redox-Bohr
      effect in this protein is associated with the acid-base equilibrium of a
      propionate of heme II instead of propionate 13 of heme I as is the case for all
      of the type I cytochromes c(3). These novel functional properties are analyzed
      together with the redox-linked structural differences reported in the literature
      and reveal a mechanistic basis for type II cytochromes c(3) having a
      physiological function that is different from that of type I cytochromes c(3).

PMID- 12203019
TI  - Is calcineurin a peroxide-specific sensor in T-lymphocytes?
AB  - Calcineurin activity in T-lymphocytes has been shown to be sensitive to H(2)O(2).
      In this report, we investigate the effects of H(2)O(2)and other physiological
      oxidants on calcineurin activity both in vivo and in vitro. Intracellular
      calcineurin activity, as determined by NF-AT phosphorylation state and activity,
      is inhibited by H(2)O(2) but is insensitive to superoxide and NaOCl. Similarly,
      treatment of T-lymphocytes with NaOCl and paraquat does not drastically alter the
      activity of calcineurin in crude cell lysate, while H(2)O(2) causes significant
      inhibition. Sensitivity to H(2)O(2) and NaOCl in vivo correlates with the half
      life of each species in cell medium. The intracellular redox potential is
      unaffected by H(2)O(2) (100 micro M) or NaOCl (600 micro M), indicating that
      H(2)O(2) inhibits calcineurin via a direct mechanism that does not involve a
      change in the cytosolic redox potential. In contrast, calcineurin activity in
      cell lysate is inhibited by all three oxidants. H(2)O(2) inactivation of
      calcineurin is rapid, with inactivation occurring in <or=10 s. H(2)O(2)
      inactivation of calcineurin is reversible in T-lymphocyte lysate using
      dithiothreitol (DTT) alone, while in rat brain lysate, reversibility requires
      both DTT and Fe(II), implicating that the enzyme may exist in different
      metal/redox-sensitive states in different tissues.

PMID- 12203020
TI  - Oxidative strand scission of nucleic acids by a multinuclear copper(II) complex.
AB  - The compound [Cu(2)(II)(D(1))(H(2)O)(2)](ClO(4))(4).2H(2)O [D(1)=binucleating
      ligand with tris(2-pyridylmethyl)amine (TMPA) moieties linked in the 5-pyridyl
      position by a -CH(2)CH(2)- bridge] mediated efficient oxidative cleavage of
      pBR322 plasmid DNA under reducing conditions. A mononuclear analogue,
      [Cu(TMPA)(H(2)O)](ClO(4))(2), was less effective at linearizing supercoiled (Form
      I) plasmid DNA as compared to the binuclear complex. A new method for quenching
      the copper-dependent reactions has been developed to avoid plasmid scission by
      the binuclear complex and the standard gel loading buffer. EDTA was not
      sufficient for retarding copper reaction, but diethyldithiocarbamic acid was
      capable of inhibiting all reactivity. Investigation of oxidative cleavage of
      double-helical oligonucleotides by [Cu(2)(II)(D(1))(H(2)O)(2)](ClO(4))(4)
      confirmed the enhanced reactivity of the binuclear over the mononuclear complex
      and provided mechanistic insights into the nature of the reaction. Cleavage of
      DNA required both the binuclear complex and a reductant and likely proceeded
      through an O(2)-derived intermediate that does not include a diffusible hydroxyl
      radical. The greater efficiency of the binuclear complex relative to the
      mononuclear analogue is consistent with their relative abilities to activate
      dioxygen.

PMID- 12203021
TI  - Copper(II)- cis, cis-1,3,5-triaminocyclohexane complex-promoted hydrolysis of
      dipeptides: kinetic, speciation and structural studies.
AB  - The hydrolysis of glycylglycine (GylGly), glycyl-L-leucine (GlyLeu), L
      leucylglycine (LeuGly) and glycyl-DL-serine (GlySer) promoted by a copper(II)-
      cis, cis-1,3,5-triaminocyclohexane complex [Cu(II)TACH] was investigated at 70
      degrees C and pH 7-10, using HPLC. The observed pseudo-first-order rate constants
      (k(obs)) and rate enhancing factors (REF) were as follows: 4.1x10(-3 )h(
      1)(REF=23) for GylGly, 1.6x10(-3 )h(-1)(REF=21) for GlyLeu, 5.1x10(-3 )h(
      1)(REF=64) for LeuGly and 9.2x10(-2 )h(-1)(REF=47) for GlySer [pH 8.1, dipeptide
      2 mM, copper(II) 2 mM and TACH 2 mM]. Based on the pH dependence and dipeptide
      concentration dependence of the initial rates and speciation of the Cu(II)-TACH
      dipeptide system at 25 degrees C and I=0.1, the reactions proceed via the
      formation of a ternary complex [Cu(TACH)(dipeptide)](+) as an intermediate
      followed by OH(-)-dependent and OH(-)-independent paths to give amino acid(s).
      GylGly, GlyLeu and LeuGly preferred the OH(-)-dependent path, while GlySer
      preferred the OH(-)-independent path. The latter can be explained by the
      intramolecular attack of the amide carbonyl group coordinated with its oxygen
      atom by the OH group in the serine residue. The X-ray crystal structure of
      [Cu(TACH)(GlyGly)]BPh(4).MeOH confirmed that GlyGly coordinates to copper(II) ion
      with its terminal amino N and amide O atoms. The crystal structures of
      [Cu(TACH)(Gly)]BPh(4) and [Cu(2)(TACH)(2)(OH)(2)](ClO(4))(2).NaClO(4).H(2)O are
      also reported.

PMID- 12203022
TI  - The biomimetic [Cr(3)O(O(2)CCH(2)CH(3))(6)(H(2)O)(3)](+ )decreases plasma
      insulin, cholesterol, and triglycerides in healthy and type II diabetic rats but
      not type I diabetic rats.
AB  - The in vivo effects of administration of the synthetic, functional biomimetic
      cation [Cr(3)O(O(2)CCH(2)CH(3))(6)(H(2)O)(3)](+) to healthy and type I and type
      II diabetic model rats are described. In contrast to current chromium-containing
      nutrition supplements, which only serve as sources of absorbable chromium, the
      trinuclear cation has been shown in in vitro assays to interact with the insulin
      receptor, activating its kinase activity, presumably by trapping the receptor in
      its active conformation. Thus, treatment of rats with the trinuclear cation would
      be expected to result in changes in lipid and carbohydrate metabolism related to
      insulin action. After 24 weeks of intravenous administration (0-20 micro g Cr/kg
      body mass), the cation results in a concentration-dependent lowering of levels of
      fasting blood plasma LDL cholesterol, total cholesterol, triglycerides, and
      insulin and of 2-h plasma insulin and glucose levels after a glucose challenge;
      these results confirm a previous 12-week study examining the effect of the
      synthetic cation on healthy rats and are in stark contrast to those of
      administration of other forms of Cr(III) to rats, which have no effect on these
      parameters. The cation has little, if any, effect on rats with STZ-induced
      diabetes (a type I diabetes model). However, Zucker obese rats (a model of the
      early stages of type II diabetes) after 24 weeks of supplementation (20 micro
      g/kg) have lower fasting plasma total, HDL, and LDL cholesterol, triglycerides,
      and insulin levels and lower 2-h plasma insulin levels. The lowering of plasma
      insulin concentrations with little effect on glucose concentrations suggests that
      the supplement increases insulin sensitivity.

PMID- 12203023
TI  - Exchange coupling constant J of peroxodiferric reaction intermediates determined
      by Mossbauer spectroscopy.
AB  - Oxygen activation at a carboxylate-bridged diiron cluster is employed by a number
      of enzymes for diverse biological functions. The mechanisms by which O(2) is
      activated at the diferrous clusters have been studied in detail and
      peroxodiferric reaction intermediates have been observed in several of these
      diiron proteins. To understand further the magnetic properties of this common
      reaction intermediate, we have used Mossbauer spectroscopy to determine the
      magnitude and sign of the exchange coupling constant J (in the exchange
      Hamiltonian J S(1) x S(2)) of the peroxodiferric intermediates generated during
      the reactions of O(2) with two different proteins, the recombinant M ferritin
      from frog and the site-directed variant W48F/D84E of the R2 subunit of
      ribonucleotide reductase from Escherichia coli. Both intermediates are
      antiferromagnetically coupled with a moderate coupling constant J of 50+/-10 cm(
      1) for R2-W48F/D84E and 75+/-10 cm(-1) for M ferritin. This work demonstrates the
      capability of Mossbauer spectroscopy to determine exchange coupling constants of
      diiron complexes, including reaction intermediates. The approach and its
      limitations are described.

PMID- 12203024
TI  - Isolation and characterization of a microperoxidase-8 with a modified histidine
      axial ligand.
AB  - Microperoxidase-8, Fe(III)MP-8, the heme octapeptide obtained by horse heart
      cytochrome c digestion, was studied in the presence of H(2)O(2). A modified form
      of the catalyst was isolated by HPLC and showed a UV/visible spectrum similar to
      that of Fe(III)MP-8. ESI-MS measurements revealed a 16 Da increase in molecular
      mass for the modified catalyst when compared to Fe(III)MP-8, suggesting the
      insertion of an oxygen atom. ESI-MS(2) fragmentation measurements point at oxygen
      incorporation on the His18 residue of the octapeptide of the modified catalyst.
      Comparison of the (1)H NMR chemical shifts of the methyl protons of the porphyrin
      ring of Fe(III)MP-8 and the modified catalyst shows a large shift for especially
      the 3-methyl and 5-methyl resonances, whereas the other (1)H NMR chemical shifts
      are almost unaffected. These observations can best be ascribed to a reorientation
      of the histidine axial ligand. The latter is suggested to be the consequence of
      an oxygen insertion, possibly on the imidazole ring of His18, thereby
      corroborating the data obtained by ESI-MS(2). (1)H NMR NOE difference
      measurements on Fe(III)MP-8 and on the modified catalyst supported the assignment
      of the H(delta)2 and H(epsilon)1 protons of the His18 imidazole ring. The ring
      amine proton H(delta)1 could not be detected in both forms of the catalyst. For
      Fe(III)MP-8 this absence of the H(delta)1 resonance can be ascribed to fast H/D
      exchange. For the modified catalyst the NMR data are not contradictory, with an
      oxygen insertion on position delta1 of the His18 imidazole ring with a fast H/D
      exchanging hydroxyl proton. Together these data converge in suggesting the
      H(2)O(2) modified catalyst bears a hydroxylated His18 axial ligand. The mechanism
      that could underlie Fe(III)MP-8 axial histidine hydroxylation is further
      discussed.

PMID- 12203025
TI  - The first non-turnover voltammetric response from a molybdenum enzyme: direct
      electrochemistry of dimethylsulfoxide reductase from Rhodobacter capsulatus.
AB  - The first direct voltammetric response from a molybdenum enzyme under non
      turnover conditions is reported. Cyclic voltammetry of dimethylsulfoxide
      reductase from Rhodobacter capsulatus reveals a reversible Mo(VI/V) response at
      +161 mV followed by a reversible Mo(V/IV) response at -102 mV versus NHE at pH 8.
      The higher potential couple exhibits a pH dependence consistent with protonation
      upon reduction to the Mo(V) state and we have determined the p K(a) for this semi
      reduced species to be 9.0. The lower potential couple is pH independent within
      the range 5<pH<10. The optical spectrum of the Mo chromophore has been
      investigated with spectroelectrochemistry. At high potential, in its resting
      state, the enzyme exhibits a spectrum characteristic of the Mo(VI) form. This
      changes significantly following bulk electrolysis (-400 mV versus NHE) at an
      optically transparent, indium-doped tin oxide working electrode, where a single
      visible electronic maximum at 632 nm is observed, which is comparable with
      spectra reported previously for the dithionite-reduced enzyme. This two-electron
      process is chemically reversible by reoxidizing the enzyme at the electrode in
      the absence of mediators or promoters. The activity of the enzyme has been
      established by observation of a catalytic current in the presence of DMSO at pH
      8, where a sigmoidal (steady state) voltammogram is seen.

PMID- 12203026
TI  - Fractionation of vanadium complexes in serum, packed cells and tissues of Wistar
      rats by means of gel filtration and anion-exchange chromatography.
AB  - Male Wistar rats were intraperitoneally injected with [(48)V]vanadium tracer to
      (1) investigate the distribution of vanadium over different tissues and (2) study
      the distribution of vanadium over the proteins and peptides in serum, packed
      cells and homogenates of tissues by means of liquid chromatography experiments
      (size exclusion, ion exchange). Target organs were primarily kidney, bone, spleen
      and liver. In serum we found that vanadium was mainly bound to transferrin;
      however, a small amount was also bound to albumin. Besides these two complexes, a
      significant part of vanadium occurred as readily exchangeable ("free") vanadium.
      In packed cells, vanadium is mainly bound to hemoglobin and to two abundant low
      molecular mass complexes. The chromatograms of tissues (kidney, liver, testes,
      spleen and lung) show similar high molecular mass complexes (vanadium co-elutes
      with ferritin, transferrin and hemoglobin). Between the low molecular mass
      complexes there are similar peaks for spleen, testes and kidneys on the one hand,
      and liver and lung on the other hand, albeit the differences are small. In the
      case of lung, there is an additional low molecular mass peak.

PMID- 12203027
TI  - The iron-binding properties of aminochelin, the mono(catecholamide) siderophore
      of Azotobacter vinelandii.
AB  - Azotobacter vinelandii produces siderophores with different metal-binding
      properties, depending on the concentration of Fe(III) and molybdate in the growth
      medium. The three protonation constants of the mono(catecholamide) siderophore
      aminochelin were determined by simultaneous spectrophotometric and potentiometric
      titrations as log K(1)=12.1, log K(2)=10.22 and log K(3)=7.04. Based on the two
      catechol protonation constants, log K(1) and log K(3), the overall stability
      constant of the aminochelin iron 3:1 complex was found to be log beta(3)=41.3,
      resulting in a pFe(3+) value of 17.6 at pH 7.45. In order to further investigate
      the properties of the siderophore, the solubilization of Fe(III) hydroxide by a
      8x10(-4) M solution of aminochelin at pH 7 and 25 degrees C was followed
      spectrophotometrically in the absence and in the presence of molybdate. It was
      observed that the addition of molybdate resulted in a significant delay in the
      solubilization.

PMID- 12203028
TI  - The H(2) sensor of Ralstonia eutropha: biochemical and spectroscopic analysis of
      mutant proteins modified at a conserved glutamine residue close to the [NiFe]
      active site.
AB  - [NiFe] hydrogenases contain a highly conserved histidine residue close to the
      [NiFe] active site which is altered by a glutamine residue in the H(2)-sensing
      [NiFe] hydrogenases. In this study, we exchanged the respective glutamine residue
      of the H(2) sensor (RH) of Ralstonia eutropha, Q67 of the RH large subunit HoxC,
      by histidine, asparagine and glutamate. The replacement by histidine and
      asparagine resulted in slightly unstable RH proteins which were hardly affected
      in their regulatory and enzymatic properties. The exchange to glutamate led to a
      completely unstable RH protein. The purified wild-type RH and the mutant protein
      with the Gln/His exchange were analysed by continuous-wave and pulsed electron
      paramagnetic resonance (EPR) techniques. We observed a coupling of a nitrogen
      nucleus with the [NiFe] active site for the mutant protein which was absent in
      the spectrum of the wild-type RH. A combination of theoretical calculations with
      the experimental data provided an explanation for the observed coupling. It is
      shown that the coupling is due to the formation of a weak hydrogen bond between
      the protonated N(epsilon) nucleus of the histidine with the sulfur of a conserved
      cysteine residue which coordinates the metal atoms of the [NiFe] active site as a
      bridging ligand. The effect of this hydrogen bond on the local structure of the
      [NiFe] active site is discussed.

PMID- 12203029
TI  - Denaturant dependence of equilibrium unfolding intermediates and denatured state
      structure of horse ferricytochrome c.
AB  - Nuclear magnetic resonance spectroscopy is employed to characterize unfolding
      intermediates and the denatured state of horse ferricytochrome c in guanidine
      hydrochloride. Unfolded and partially unfolded species with non-native heme
      ligation are detected by analysis of hyperfine-shifted (1)H resonances. Two
      equilibrium unfolding intermediates with His-Lys heme axial ligation are
      detected, as are two unfolded species with bis-His heme ligation. These results
      are contrasted with previous results on horse ferricytochrome c denaturation by
      urea, for which only one unfolding intermediate and one unfolded species were
      detected by NMR spectroscopy. Urea and guanidine hydrochloride are often used
      interchangeably in protein denaturation studies, but these results and those of
      others indicate that unfolded and intermediate states in these two denaturants
      may have substantially different properties. Implications of these results for
      folding studies and the biological function of mitochondrial cytochromes c are
      discussed.

PMID- 12203030
TI  - Crystal ghosts and biological mineralization: fancy spectres in an old castle, or
      neglected structures worthy of belief?

PMID- 12203031
TI  - A novel therapeutic vaccine approach, targeting RANKL, prevents bone destruction
      in bone-related disorders.

PMID- 12203033
TI  - Ultrasound detection of trypsin-treated articular cartilage: its association with
      cartilaginous proteoglycans assessed by histological and biochemical methods.
AB  - We studied the correlation between histological imaging quantification and the
      biochemical assessment of proteoglycan (PG) content in articular cartilage in
      vitro, which served as a basis for the validation of ultrasound detection as a
      noninvasive tool in the assessment of PG changes in full-thickness articular
      cartilage. Articular cartilage of 14 intact fresh bovine femoral condyles was
      used for trypsin digestion. Full-thickness articular cartilage cylinders, 3 mm in
      diameter, were harvested at time intervals of 0.5, 1, 2, and 3 h after trypsin
      digestion. Each cartilage cylinder was then cut into two equal parts for either
      histomorphometric quantification of the PG area fraction stained with Safranine O
      or conventional biochemical assessment of uronic acid content. In addition, five
      fresh mature bovine patellae were used for the validation of an ultrasound
      compression system developed for testing the potential layered biomechanical
      properties of articular cartilage, including the equilibrium compressive modulus,
      i.e., the slope of the linear regression of the equilibrium stress-strain curve.
      Results showed that PG content in the articular cartilage was significantly
      decreased with increasing time of trypsin digestion, both histologically and
      biochemically, with a significant correlation of r = 0.502 ( P < 0.001).
      Ultrasound measurements demonstrated differences in the equilibrium compressive
      moduli of the digested zone, the undigested zone, and the entire articular
      cartilage layer, as well as a characteristically large ultrasound reflection
      signal detected in the interface of the trypsin digestion front of articular
      cartilage. The results of this study suggested that the histomorphometric
      quantification of PG content could be used to reflect not only PG quantity but
      also its spatial distribution; also, the ultrasound compression system might have
      potential for the non-invasive detection of pathological changes in articular
      cartilage.

PMID- 12203032
TI  - Coordinate gene expression patterns during osteoblast maturation and retinoic
      acid treatment of MC3T3-E1 cells.
AB  - The clonal osteoblast-like cell line MC3T3-E1 undergoes time-dependent
      morphological changes leading to the formation of bone nodules in vitro. Serial
      analysis of gene expression was used to identify genes expressed in MC3T3-E1
      cells, including known osteoblast markers, structural and matrix proteins,
      transcription factors, cell-cycle regulators, and housekeeping genes. Relative
      changes in the expression of 92 representative transcripts were determined by
      arrayed cDNA hybridization. Complex probes were derived from MC3T3-E1 cells
      during the proliferation, differentiation, and matrix mineralization stages, and
      from cells grown with all- trans-retinoic acid (RA), a potent bone morphogen. We
      found that the relative expression of 68 of these genes was higher during
      differentiation than in the earlier proliferative phase. In the mineralization
      phase, all but 16 cDNAs had lower normalized hybridization intensity ratios as
      compared with the differentiation phase. cDNAs for vimentin (Vim), presenilin 2
      (Psen2), guanine nucleotide binding protein alpha stimulating (Gnas), gap
      junction membrane channel protein beta 1 (Gjb1), fibroblast growth factor
      receptor 1 (Fgfr1), eukaryotic translation elongation factor 2 (Eef2), and
      calponin 2 (Cnn2) had higher normalized hybridization intensities in both
      differentiation and mineralization than in proliferation. RA treatment during the
      differentiation phase appeared to reduce the expression of the 92 genes examined,
      as 62 cDNAs had lower hybridization intensities with complex cDNA probes derived
      from RA-treated cells than with the probe from untreated cells. Several cDNAs
      representing genes with previously unrecognized RA responsiveness were identified
      by this comparison, including the receptor for bone morphogenetic proteins 2 and
      4 (Bmp2/Bmp4) and hemoglobin Y.

PMID- 12203034
TI  - Ultrastructural localization of proteoglycans in bone in osteogenesis imperfecta
      as demonstrated by Cuprolinic Blue staining.
AB  - The role of proteoglycans in bone in osteogenesis imperfecta (OI) has been
      examined. Using Cuprolinic Blue staining of whole fetal bone tissue and examining
      the tissue in the transmission electron microscope, the presence of proteoglycans
      was observed. Quantitative comparative image-analysis of the proteoglycans from
      electron micrographs was performed, with measurement of sizes and number of
      proteoglycan particles. A significant increase in the total number of
      proteoglycan particles in OI bone osteoid was observed when compared with normal,
      matched controls. The area of the proteoglycan particles, as measured by pixel
      area, using image analysis, was also increased in OI bone osteoid. These findings
      further suggest a role for proteoglycans in mineral formation by the possible
      inhibition of mineral growth and alteration of collagen nucleation sites. The
      increased number and size of proteoglycan particles may be a contributing factor
      to the previously reported poor mineral formation with subsequent loss of bone
      strength, making it more prone to fracture, in OI.

PMID- 12203035
TI  - Bone mineralization in Turner syndrome: a transverse study of the determinant
      factors in 58 patients.
AB  - Turner syndrome (TS) is characterized by the presence of an X chromosome and
      total or partial loss of the second sex chromosome, short stature,
      hypergonadotrophic hypogonadism, and a variable dysmorphic picture. Delayed
      puberty and estrogen deficiency are some of the determinant factors of
      osteoporosis in TS, but the whether or not there is an intrinsic bone defect is
      still obscure. The aim of this study was to evaluate the correlation of the z
      score of bone mineral density (BMD) with age, weight, height, karyotype,
      associated diseases, bone age, and estrogen therapy in TS patients. We performed
      a transverse study with area BMD of L2-L4 with dual-energy X-ray absorptiometry
      (DEXA) in 58 patients with a cytogenetic diagnosis of TS, whose ages ranged from
      5 to 29 years. It was observed that 86% of the patients presented with a BMD z
      score below -1 SD, and 46.5% with a value below -2.5 SD. There was a significant
      negative association of BMD with age and height, and a positive association with
      weight and bone mass index (BMI) z scores. A higher BMD was observed in patients
      with spontaneous puberty and in those with more than 2 years of hormone
      replacement. In conclusion, there was a high incidence of reduced bone mass among
      our patients, which was influenced by weight and BMI, by the use and the time of
      estrogen replacement, and by the presence of spontaneous puberty.

PMID- 12203036
TI  - The effect of active absorbable algal calcium (AAA Ca) with collagen and other
      matrix components on back and joint pain and skin impedance.
AB  - The effect of active absorbable algal calcium (AAA Ca) with collagen and other
      matrix components on aging-associated skin changes and backache and joint pain
      was tested in a case-controlled study of 40 test subjects and 40 age-matched
      control subjects (mean age, 65 years) complaining of backache and knee joint pain
      due to osteoarthritis, spondylosis deformans, and/or osteoporosis.
      Supplementation with 900 mg calcium (given as AAA Ca) and 3.5 g collagen and
      other matrix components, including glucosamine, daily for 4 months resulted in a
      marked alleviation of subjective pain, assessed by the face scale. A fall of skin
      impedance in response to exercise loads, such as standing up, walking, squatting,
      and climbing up and down stairs, reported as an objective manifestion of pain,
      was also alleviated. The basal skin impedance, which increases with age, was
      significantly reduced in response to the Ca-collagen-matrix supplementation,
      suggesting a change of skin properties similar to rejuvenation, along with
      subjective smoothening and moistening of the skin. Urinary excretion of N
      terminal crosslinking telopeptide of type I collagen (NTx) was decreased in the
      Ca-collagen-matrix supplementation group, but not in the control group. In
      addition to calcium suppression of parathyroid hormone, preventing bone
      resorption, collagen, acting on the intestinal lymphatic system, may protect
      collagen from degradation through the inhibition of cytokine-induced release of
      metalloproteinases, including collagenase.

PMID- 12203037
TI  - The relationship between endogenous estrogen, sex hormone-binding globulin, and
      bone loss in female residents of a rural Japanese community: the Taiji Study.
AB  - The aim of this study was to clarify the relationship between endogenous
      estrogen, sex hormone-binding globulin (SHBG), and bone loss in pre-, peri-, and
      postmenopausal female residents of Taiji, a rural Japanese community. From a list
      of inhabitants aged 40 to 79 years, 200 participants-50 women in each of four age
      decades-were randomly selected, and baseline bone mineral density (BMD) at the
      lumbar spine and proximal femur were measured by dual-energy X-ray absorptiometry
      in 1993. Total estradiol (total E2) and SHBG were measured, and SHBG-unbound E2
      (UBE2) was calculated using SHBG and the percent SHBG-unbound fraction ratio. BMD
      was measured again 3 years later, in 1996. Participants with ovariectomy or
      hysterectomy were excluded, and the remaining participants were categorized into
      four groups: premenopausal ( n = 38), perimenopausal ( n = 14), postmenopausal
      group 1 (5 years or less since menopause; n = 18), and postmenopausal group 2 (6
      years or more since menopause; n = 74). The mean value of total E2 was highest in
      the premenopausal group (49.1 pg/ml), followed by the perimenopausal group (26.4
      pg/ml), and the postmenopausal groups (0.83 pg/ml in postmenopausal group 1 and
      0.96 pg/ml in postmenopausal group 2). The means for UBE2 showed the same pattern
      across the groups. After the multiple regression analysis of BMD at follow-up and
      endogenous estrogens, in premenopausal women, there were no significant
      associations between BMD at follow-up and serum total E2 and UBE2. In
      perimenopausal women, however, serum total E2 and UBE2 were significantly
      correlated with trochanteric BMD at follow-up ( P < 0.05); and in postmenopausal
      group 2, they were significantly correlated with lumbar spine and Ward's triangle
      BMD at follow-up ( P < 0.001 at lumbar spine, P < 0.05 at Ward's triangle).
      Concerning the association between BMD at follow-up and SHBG, in the
      premenopausal group, serum levels of SHBG were negatively correlated with BMD at
      the femoral neck ( P < 0.05). In regard to partial regression coefficients for
      the change rates of BMD over 3 years and serum estrogens and SHBG concentrations,
      in perimenopausal women, UBE2 was correlated with the change rate of BMD at
      Ward's triangle ( P < 0.05), and in postmenopausal group 1, serum levels of SHBG
      were significantly negatively related to change in BMD at the trochanter ( P <
      0.01). No other relationships with change in BMD were observed at any sites.
      These findings suggest that serum E2, UBE2, and SHBG levels differentially
      predict BMD levels in groups of differing menstrual status. It would, however, be
      difficult to predict bone loss in middle-aged and elderly Japanese women over a 3
      year period using these indices alone.

PMID- 12203038
TI  - The incidence of cervical and trochanteric fractures of the proximal femur in
      1999 in Niigata Prefecture, Japan.
AB  - The purpose of this study was to determine the incidence of cervical and
      trochanteric fractures of the proximal femur in 1999 in Niigata Prefecture,
      Japan, and to compare this incidence with those previously reported in Niigata in
      1985, 1987, 1989, and 1994. The authors visited all hospitals within Niigata
      Prefecture having an orthopedic department and reviewed the medical records and
      radiographs of all patients who sustained such fractures in 1999. The population
      of Niigata Prefecture was determined in 1999 to be 2 486 999 (1 208 195 males and
      1 278 804 females). The population over 65 years of age was 515 290 (210 564
      males and 304 726 females), representing 20.7% of the total population. In 1999,
      there were 1697 cervical or trochanteric fractures, in 400 males and 1297
      females, with a male-to-female ratio of 1 : 3.2. The incidence of these fractures
      in persons over 65 years of age was 308.7 fractures per 100 000 per year. This
      incidence increased from 1985 to 1989 and from 1989 to 1994, but after that, the
      rate of increase in incidence from 1994 to 1999 slowed down slightly. This
      suggests that the prevention of fractures in the elderly population in Niigata
      Prefecture influenced the lower ratio.

PMID- 12203039
TI  - AMPA receptor subunit RNA transcripts and [(3)H]AMPA binding in the cerebellum of
      normal and pcd mutant mice: an in situ hybridization study combined with receptor
      autoradiography.
AB  - The expression of AMPA receptor subunit mRNAs and the binding of [(3)H]AMPA were
      studied in the cerebellum of normal and "Purkinje cell degeneration" ( pcd)
      mutant mouse. In the pcd cerebellum, [(3)H]AMPA binding was decreased
      significantly in both the molecular and granule cell layers by 63% and 36%,
      respectively. In those mutants, GluRA, GluRB and GluRC mRNAs were not detected in
      the Purkinje cell layer, and the levels of GluRB and GluRD mRNAs were
      significantly decreased in the granule cell layer by 16% and 57%, respectively.
      Cerebellar grafts transplanted into the pcd cerebellum expressed only GluRB and
      GluRC mRNAs, suggesting that donor cells express the appropriate subunits
      normally expressed by Purkinje neurons. Our results, firstly, support the idea
      that the expression of the GluRA subunit in Golgi epithelial cells may depend
      upon the sustained interaction with adjacent Purkinje cells, and secondly,
      suggest that granule cells which are more resistant to transsynaptic death may
      express higher levels of GluRB mRNA.

PMID- 12203040
TI  - Postnatal rearing conditions influence ontogeny of adult dopamine transporter
      (DAT) immunoreactivity of the striatum in gerbils.
AB  - In the present study, the influence of postnatal rearing conditions on the
      structural maturation of the striatum of adult male gerbils (Meriones
      unguiculatus) was investigated. For that purpose, animals were bred and reared
      either grouped in an object-filled environment (EC) or isolated under restricted
      environmental conditions (IC). At the age of postnatal day 90, dopamine fibers
      were stained immunocytochemically using an antibody against the dopamine
      transporter (DAT). Innervation density was determined along the entire
      rostrocaudal axis of the ventromedial and dorsolateral part of the striatum. As a
      result, restricted rearing produced a significant restraint of the maturation of
      striatal dopamine (DA) innervation, leading to adult fiber densities which were
      approximately 9% below those in semi-naturally reared gerbils. Results are
      discussed with structural and functional alterations observed in the brain of IC
      animals.

PMID- 12203041
TI  - Effects of rolipram on in vivo dopamine receptor binding.
AB  - In order to clarify whether changes in brain concentrations of the second
      messenger cyclic AMP (cAMP) affect in vivo receptor binding in the brain, the
      effects of rolipram, a selective inhibitor of phosphodiesterase type 4 (PDE(4)),
      on dopamine receptor binding in the mouse brain were studied. Rolipram
      significantly decreased in vivo (3)H-SCH 23390 (dopamine D(1) selective
      radioligand) binding in the mouse striatum in a dose-dependent manner. In vivo
      saturation experiments together with the kinetic analysis of (3)H-SCH 23390
      binding revealed that the apparent association rate constant (k(on)) for (3)H-SCH
      23390 binding rather than the maximum number of binding sites available (B(max))
      was decreased by rolipram. (3)H-N-methylspiperone (NMSP, dopamine D(2) selective
      radioligand) binding in the mouse striatum was also decreased by rolipram whereas
      no significant changes in (3)H-raclopride (dopamine D(2) selective radioligand)
      binding were observed. As (3)H-raclopride binding has been reported to be much
      more sensitive than (3)H-NMSP binding to competition by endogenous dopamine, the
      decreases in (3)H-SCH 23390 and (3)H-NMSP binding cannot be attributed to
      competitive inhibition by endogenous dopamine. These results indicate that
      changes in second messenger cAMP concentrations may affect the apparent
      bimolecular association rate constant (k(on)) of dopamine receptor binding in
      intact brain. This may be mediated by changes in the receptor micro-environment
      and altered actual free ligand concentration surrounding the receptors.

PMID- 12203042
TI  - Acute changes in dopamine release and turnover in rat caudate nucleus following a
      single dose of methamphetamine.
AB  - Acute changes in dopamine (DA) turnover were studied in the caudate nucleus (CN)
      of adult male rats between 0-24 h after a single injection of Methamphetamine (20
      mg/kg, ip). A single dose of METH-induced an increase in DA turnover [(DOPAC +
      HVA)/DA] concomitant with an acute DA release followed by transient DA and DOPAC
      depletion in the rat CN.

PMID- 12203043
TI  - Dopamine efflux by MPTP and hydroxyl radical generation.
AB  - 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) produces a parkinsonian
      syndrome after its conversion to 1-methyl-4-phenylpyridine (MPP(+)) by B-form
      monoamine oxidase (MAO) in the brain, which is one of the most potent dopamine
      (DA)-releasing agents. MPP(+) perfusion into the striatum increases extracellular
      DA levels and this increase may concomitantly induce the formation of reactive
      free oxygen radicals, such as hydroxyl radical (.OH). These elevations seem to
      induce lipid peroxidation of striatum membranes, as detected by increases non
      enzymatic formation of 2,3-dihydroxybenzoic acid (DHBA) levels. Sustained
      increase in striatal DA efflux by MAO inhibition produce.OH generation by
      products of monoamine. Therefore, reserpine-induced DA depletion clearly
      decreased MPP(+)-induced.OH formation. Neuromelanine synthesis from DA produce
      highly reactive free radicals. Nitric oxide (NO) contributes to produce MPP(+)
      induced.OH generation via NO synthase (NOS) activation by depolarization. The
      antioxidation effect of angiotensin converting enzyme (ACE) inhibitor protects
      against MPP(+)-induced.OH generation due to the suppression of the Ca(2+)
      dependent release of DA. These findings may be useful in elucidating the actual
      mechanism of free radical formation in the pathogenesis of neurodegenerative
      brain disorders, including Parkinson's disease and traumatic brain injuries. This
      review describes the free radicals mechanisms involved in MPTP toxicity and their
      possible involvement in the the pathogenesis of Parkinson's disease.

PMID- 12203044
TI  - Mutation analysis and association studies of nuclear factor-kappaB1 in sporadic
      Parkinson's disease patients.
AB  - Biochemical and morphological studies revealed that oxidative stress and
      apoptosis play a role in neurodegeneration in Parkinson's disease (PD). Reactive
      oxygen species may be directly involved in apoptosis or via upregulation of toxic
      cytokines, i.e. tumor necrosis factor alpha (TNFalpha). We recently demonstrated
      that the TNFalpha pathway contributes to the pathogenesis of sporadic PD using a
      genetic approach. These signalling pathways converge to the transcription factor
      nuclear factor kappaB (NF-kappaB), which has been found activated in affected
      neurons in PD. We performed a detailed mutation analysis of the p50 subunit of NF
      kappaB (NFKB1 gene) in 96 sporadic PD patients. Previously, positive association
      was demonstrated in this cohort to chromosome 4q21-23 containing the NFKB1 gene.
      We identified three base exchanges not affecting the amino acid sequence, which
      were found at similar frequencies in controls. Our study does not support a
      genetically definable role of NFKB1 in the pathogenesis of sporadic PD.

PMID- 12203045
TI  - Mutation analysis of the sodium/hydrogen exchanger gene (NHE5) in familial
      paroxysmal kinesigenic dyskinesia.
AB  - Familial Paroxysmal Kinesigenic Dyskinesia (PKD) is an autosomal dominant
      condition characterized by attacks of dystonia or chorea triggered by sudden
      movements. Recently two separate loci for PKD, Episodic Kinesigenic Dyskinesia 1
      (EKD1) and Episodic Kinesigenic Dyskinesia 2 (EKD2), have been mapped to
      chromosome 16 but the causative genes have not been identified. The Na(+)/H(+)
      exchanger gene (NHE5) involved in regulating intracellular pH lies in the EKD2
      region. The coding region of the NHE5 gene in familial PKD was sequenced. We did
      not identify any mutations in the exons, intron/exon boundaries or the 5' and
      3'UTR. This excludes mutations in the coding region of the NHE5 gene as a cause
      for familial PKD, but does not rule out a possible role of sequence variants in
      introns or regulatory regions.

PMID- 12203047
TI  - Alzheimer's disease is not associated with altered concentrations of the nitric
      oxide synthase inhibitor asymmetric dimethylarginine in cerebrospinal fluid.
AB  - Nitric oxide (NO) may play a role in the pathophysiology of Alzheimer's disease
      (AD). Asymmetric dimethylarginine (ADMA), an endogenous inhibitor of NO synthase,
      is involved in regulation of NO production. Recently it has been reported that
      dimethylarginine dimethylaminohydrolase, an enzyme that hydrolyses ADMA into
      citrulline and dimethylamine, is specifically elevated in neurons displaying
      cytoskeletal abnormalities and oxidative stress in AD. We hypothesized that this
      could lead to altered CSF concentrations of ADMA in AD. Measurement of ADMA and
      dimethylamine in CSF revealed no significant differences between AD patients (n =
      20) and age-matched control subjects (n = 20). Our results suggest that in early
      stages of AD overall regulation of NO production by ADMA is not aberrant.

PMID- 12203046
TI  - Serum levels of coenzyme Q in patients with Lewy body disease.
AB  - The purpose of the present study was to compare serum levels of coenzyme Q(10)
      (CoQ(10)) and the coenzyme Q(10) cholesterol (CoQ(10)/cholesterol) ratio in 18
      patients with Lewy body disease (LBD) with 20 matched controls. The mean serum
      coenzyme Q10 levels in patients with LBD were significantly reduced with respect
      to control group, however, no differences were found in CoQ(10)/cholesterol ratio
      between LBD patients and control group. There was no correlation among CoQ(10)
      and CoQ(10)/cholesterol ratio with age, age of onset, body mass index, duration
      of the disease or scores of the Mini Mental State Examination, UPDRS and Hoehn
      and Yahr stage. These results suggest the involvement of this enzimatic system in
      the pathogenic mechanism of LBD.

PMID- 12203048
TI  - Association study of angiotensin I-converting enzyme polymorphism and
      symptomatology and antidepressant response in major depressive disorders.
AB  - Angiotensin-converting enzyme (ACE) inhibitor has mood-elevating effects, and
      central ACE activity is increased for suicidal patients. In addition, substance P
      (SP), which is degraded by ACE, has been implicated in the pathogenesis of, and
      evaluated in the treatment for, major depressive disorder (MDD). The present
      study has tested the hypothesis that an ACE-gene insertion/deletion (I/D)
      polymorphism is associated with onset age, clinical manifestations, suicide
      history, and/or antidepressant response for two groups of MDD patients. No
      significant differences were demonstrated for onset age (p = 0.520), suicide
      history (p = 0.823), or baseline, total and cluster scores for Hamilton
      Depression Rating Scale comparing the three ACE genotypes. Further, previous
      findings that this ACE polymorphism is associated with therapeutic antidepressant
      effects were not replicated. The results demonstrate that these ACE variants did
      not play a major role in the clinical manifestations or antidepressant response
      for our MDD patients.

PMID- 12203049
TI  - Different striatal dopamine D2 receptor occupancy in alcohol dependent patients
      with or without physical withdrawal symptoms --a study using IBZM-SPECT.
AB  - Ten male patients with type I alcohol dependency fulfilling DSM-IV criteria for
      alcohol dependency were investigated twice using IBZM-SPECT after alcohol
      withdrawal (day 2 and day 28 after withdrawal). Five patients had a history of
      physical withdrawal symptoms, 5 patients had no such history. The group with
      physical withdrawal symptoms showed higher IBZM binding in both scans indicating
      differences of dopaminergic neurotransmission in different subtypes of alcohol
      dependency.

PMID- 12203050
TI  - Effects of U-50,488H, a kappa-opioid receptor agonist, on the learned
      helplessness model of depression in mice.
AB  - We investigated the effects of U-50,488H, a kappa-opioid receptor agonist, on the
      learned helplessness model of depression in mice. Mice pre-exposed to inescapable
      electric footshock were treated with U-50,488H. Stimulation of the kappa-opioid
      receptor by U-50,488H (10 mg/kg/day, i.p.) attenuated the escape failure induced
      by pre-exposure to shock. This attenuation by U-50,488H was blocked by MR2266 (10
      mg/kg/day, s.c.), an opioid receptor antagonist. These results suggest that the
      kappa-opioid system plays an important role in the learned helplessness
      depression in mice.

PMID- 12203051
TI  - Expression of vascular endothelial growth factor family messenger RNA in diseased
      thyroid tissues.
AB  - PURPOSE: Four different factors have recently been identified in the vascular
      endothelial growth factor (VEGF)family, namely, VEGF-A, VEGF-B, VEGF-C, and VEGF
      D. We investigated the expression of each VEGF gene in diseased thyroids using
      the multiplex reverse transcription-polymerase chain reaction (RT-PCR) method.
      METHODS: The subjects were 61 patients (11 with Graves' disease, 41 with primary
      papillary carcinoma, and 9 with recurrent papillary carcinoma). A
      semiquantitative multiplex RT-PCR was designed to compare the RT-PCR products of
      each VEGF mRNA with beta-actin mRNA products to determine the relative
      expression. RESULTS: VEGF-A and VEGF-B mRNA were expressed in all patients, VEGF
      C mRNA was expressed in 58 (95.1%), and VEGF-D mRNA was expressed in 28 (46.0%).
      The expression of VEGF-D mRNA was significantly lower than that of the other VEGF
      mRNAs. The patients with papillary carcinoma and nodal involvement had
      significantly higher expression of the VEGF-C mRNA than those without nodal
      involvement. The expression of VEGF-C mRNA did not directly represent nodal
      involvement; however, the number of metastatic lymph nodes was positively
      correlated with the expression of VEGF-C mRNA in the primary tumor. CONCLUSIONS:
      To our knowledge, this is the first clinical study on VEGF-B, VEGF-C, and VEGF-D
      mRNA expression in diseased thyroids. Although VEGF-C mRNA expression was
      required for nodal involvement, we assume that other factors and mechanisms are
      also involved.

PMID- 12203052
TI  - Analysis of chest injuries sustained during the 1999 Marmara earthquake.
AB  - PURPOSE: The chest injury pattern after a major earthquake is not well understood
      because data on the type of trauma and surgical intervention are limited. This
      study was conducted to analyze patients who sustained chest injury during the
      Marmara earthquake that struck Turkey on August 17, 1999 registering 7.4 on the
      Richter scale. METHODS: The medical reports of 528 patients transported to a
      military hospital in the first 48 h after the earthquake were reviewed. Two chest
      surgeons examined these 528 patients, 19 of whom (4%) had suffered a major chest
      injury. We retrospectively evaluated the injury pattern, Abbreviated Injury Score
      (AIS), and Injury Severity Score (ISS) in these 19 patients. RESULTS: Eight
      patients (42%) had isolated chest injuries and 11 (58%) had suffered injury to
      more than one organ system, including chest trauma. The mean AIS and ISS were
      assigned as 2.9 (SD: 1) and 22 (SD: 7), respectively. Three (16%) of the 19
      patients died, all of whom had suffered multiple injuries. The mean ISS of these
      three patients was 28.7 (range 25-34). Chest injury after a major earthquake was
      associated with an overall mortality rate of 16%, but chest injury with multiple
      injuries and an ISS over 25 was associated with a mortality rate of 60%. All
      patients with isolated chest injuries survived. CONCLUSION: Coexistent trauma
      with chest injury and an ISS over 25 were defined as poor prognostic factors for
      patients rescued after a major earthquake.

PMID- 12203053
TI  - Feasibility of induction chemotherapy using bronchial arterial infusion for
      locally advanced non-small cell lung cancer: a pilot study.
AB  - PURPOSE: We examined the feasibility and effectiveness of bronchial arterial
      infusion (BAI) as induction chemotherapy before surgery for locally advanced non
      small cell lung cancer (NSCLC). METHODS: Eighteen patients with locally advanced
      NSCLC were given BAI consisting of cis-diamminedichloroplatinum (CDDP) (50-100
      mg/m(2)) as induction chemotherapy before surgery (induction BAI). Six patients
      with clinical stage IIIA cancer had bulky N2 metastatic lymph nodes, and 12
      patients with clinical stage IIIB cancer had T4 disease. RESULTS: Of the 18
      patients, 12 (67%) showed a partial response to the BAI therapy. Standard
      pulmonary resection was performed in 5 patients, pulmonary resection with the
      combined resection of adjacent organs was performed in 10 patients, and pulmonary
      resection with carinal resection and reconstruction was performed in 3 patients.
      Complete resection was possible in 14 patients (78%). There were no serious BAI
      therapy-related complications or postoperative deaths. The 5-year survival rate
      of the 18 patients was 35.7% and the median survival time (MST) was 19.4 months.
      Survival was better when complete resection was achieved after the induction BAI,
      especially in patients with stage IIIB (T4) disease. CONCLUSION: Based on our
      preliminary findings, BAI with CDDP as induction chemotherapy is feasible and may
      be an effective therapeutic modality for locally advanced NSCLC.

PMID- 12203054
TI  - Conservative surgical treatment of pulmonary hydatid disease in children: an
      analysis of 35 cases.
AB  - PURPOSE: Hydatid cyst disease is a major health problem for people who live in
      endemic countries such as Turkey. The definitive cure for pulmonary hydatidosis
      is still surgical. This study evaluates our experience of treating pulmonary
      hydatidosis, focusing on the conservative surgical management of children with
      this disease. METHODS: We retrospectively analyzed 35 children ranging in age
      from 3 to 13 years old, treated for pulmonary hydatidosis during a recent 4-year
      period. RESULTS: The 35 patients had a collective total of 48 cysts. Twenty-seven
      patients had a single cyst, 7 had unilateral multiple cysts, and 1 had bilateral
      multiple cysts. Six patients had multiple coexisting liver cysts. The 33
      pulmonary cysts were intact and uncomplicated. Of the total 48 cysts, 34 were
      larger than 5 cm in diameter. Fever, cough, and dyspnea were the most common
      symptoms and chest radiography gave a correct diagnosis in 96.4% of the patients.
      Conservative surgical treatment was carried out in 33 of the 35 children (94%).
      There were few postoperative complications, and no mortality or recurrence in
      this series. CONCLUSIONS: Parenchyma-saving surgical procedures such as cystotomy
      and capitonnage are the preferred methods of treatment for pulmonary hydatid
      disease in childhood. These simple procedures are safe, reliable, and successful.
      Combined medical treatment can be given but not as an alternative to surgery.
      Simultaneous surgical procedures for coexisting liver cysts may be preferred
      because of the lower morbidity rates and hospitalization. Ultrasound or computed
      tomography scanning should be done to detect coexisting liver cysts in every
      patient with pulmonary hydatid disease.

PMID- 12203055
TI  - The effectiveness of palliative resection for advanced esophageal carcinoma:
      analysis of 24 consecutive cases.
AB  - PURPOSE: In some patients who already have advanced esophageal cancer at the time
      of presentation, symptoms like the inability to eat, and complications such as
      bronchoesophageal fistula are so debilitating that palliative resection may be
      beneficial. However, resection of the esophagus is associated with significant
      risk, and whether this operation should be performed for palliation remains
      controversial. Because few reports have been published on this subject, we
      retrospectively analyzed 24 patients with esophageal cancer who underwent
      palliative resection. METHODS: Esophageal resection was performed with palliative
      intent in 12 patients and with curative intent in another 12 who were left with
      residual cancer. RESULTS: There was no operative death. All of the ten patients
      who had been unable to eat preoperatively were able to eat after the operation,
      and four patients with a life-threatening bronchoesophageal fistula were free of
      symptoms after the operation. Two patients died in hospital during the
      postoperative chemotherapy but the other 22 were discharged. The mean survival
      period was 264 days. CONCLUSIONS: With improved postoperative care, the risk of
      palliative esophageal resection is no longer considered unacceptable.

PMID- 12203056
TI  - Surgical procedures for digestive fistulae caused by radiation therapy.
AB  - PURPOSE: We evaluated the effectiveness of surgery to treat ileal fistulations
      associated with radiation exposure. SUBJECTS. An ileal fistula developed in eight
      patients, 13-102 months after 60 Gy of irradiation to the pelvic cavity, given as
      initial treatment or supportive therapy following resection of the primary tumor.
      The underlying diseases were cervical cancer in seven women and bladder cancer in
      one man. RESULTS: Two patients had an ileorectal fistula, two had an
      ileosigmoidal fistula, three had an ileovesical fistula, and one had an
      ileourethral fistula. We performed a partial enterectomy in one patient, a simple
      bypass operation without exclusion in one, and bypass operations with exclusion
      in the other six. Intestinal expansion in the exclusion site occurred in one
      patient, but there were no other complications related directly to surgery, such
      as sutural insufficiency. The patient who underwent a simple bypass operation
      died of emaciation 2 months after the surgery, but all of the other patients were
      discharged capable of oral ingestion. CONCLUSION: Our findings showed that
      surgery was beneficial for alleviating the various conditions related to
      digestive fistulation following radiation therapy.

PMID- 12203057
TI  - Influence of cold ischemia time and graft transport distance on postoperative
      outcome in human liver transplantation.
AB  - PURPOSE: The association between hepatic allograft cold ischemia time (CIT) and
      graft transport distance (GTD) in human liver transplantation was examined by
      investigating whether extended graft transportation prolongs the CIT and
      adversely affects graft survival. METHODS: We retrospectively analyzed 186
      consecutive orthotopic liver transplants (OLTs) done between May 1997 and July
      1998. The number of miles from the donor hospital to the University of Pittsburgh
      Medical Center in a straight line was measured in each case, and defined as the
      GTD. The OLTs were divided into two groups according to whether the GTD was
      </=200 miles or >200 miles. The latter group was then subdivided into groups of
      GTD 200-400 miles, GTD 400-600 miles, and GTD >600 miles. The CIT and graft
      outcome within 90 days after OLT were assessed. RESULTS: Extended GTD prolonged
      the CIT ( P < 0.001). The rate of hepatic allograft loss in the long GTD group
      was significantly higher than that in the short GTD group ( P = 0.018). When the
      OLTs were subdivided according to GTD, the CIT increased and graft survival
      decreased as the GTD extended. Hepatic allograft transportation for a long
      distance prolonged the CIT and decreased the graft survival rate. CONCLUSION:
      Since prolonged CIT is a major risk factor, avoiding long-distance graft
      transportation is recommended when the donor risk factors are high.

PMID- 12203058
TI  - A pediatric amino acid solution for total parenteral nutrition does not affect
      liver function test results in neonates.
AB  - PURPOSE: We studied the effects of an amino acid mixture used for total
      parenteral nutrition (TPN) in pediatrics, on the liver function test results
      (LFTs) of neonates. METHODS: Thirty neonatal surgical patients were randomly
      divided into three groups according to the dose of amino acids given: group H ( n
      = 12, 3.45 +/- 0.07 g/kg per day), group M ( n = 8, 2.59 +/- 0.07 g/kg per day),
      and group L ( n = 10, 1.72 +/- 0.06 g/kg per day). All patients received the same
      amount of dextrose (average 21.5 g/kg per day) and no lipid. RESULTS: There were
      no significant differences in LFTs, namely, direct bilirubin, glutamic
      oxaloacetic transaminase, glutamic pyruvic transaminase, alkaline phosphatase,
      gamma-glutamyl transpeptidase, and total bile acids, among the three groups on
      the tenth day of TPN. CONCLUSION: These findings indicate that this amino acid
      solution for pediatrics has no significant effect on LFTs in neonates, even when
      high doses of amino acids (3.5 g/kg per day) are infused.

PMID- 12203059
TI  - Interposition of a jejunal segment as an alternative one-stage operation for
      acute left colon obstruction.
AB  - PURPOSE: Much debate surrounds the one-stage surgical management of acute left
      colon obstruction. Many surgeons are still reluctant to perform primary
      anastomosis in unprepared bowel fearing the risk of anastomotic dehiscence.
      Although intraoperative lavage and subtotal colectomy have recently proved
      effective for preventing fecal loading, both of these procedures have drawbacks
      and the search for additional alternative surgical procedures continues. We
      conducted an experimental study to examine a new one-stage operation, consisting
      of the interposition of a jejunal segment to the resection site of the colon, to
      manage acute left colon obstruction. METHODS: The colons of 20 domestic pigs were
      obstructed, and 2 days later, segmental resection and either primary colo-colonic
      anastomosis or interposition of a jejunal segment was performed. Autopsies were
      done 6 weeks after the operations and the anastomotic regions were subjected to
      bursting pressure analysis. RESULTS: The operating time was longer in the
      interposition group at 49 +/- 14 vs 38 +/- 12 min ( P < 0.01). There was no
      mortality or clinical signs of anastomotic dehiscence in either group. A
      perianastomotic abscess was detected on autopsy in one animal from the primary
      colo-colonic anastomosis group. The bursting pressures of the jejunocolic
      anastomoses were significantly higher ( P < 0.001) than those of the primary colo
      colonic anastomoses. CONCLUSIONS: These experimental results suggest that jejunal
      interposition may be a feasible alternative to primary colonic anastomosis to
      create intestinal continuity after resection for acute obstruction of the left
      colon.

PMID- 12203060
TI  - Parathyroid adenoma manifested by mediastinal hemorrhage: report of a case.
AB  - Acute mediastinal hemorrhage is rarely caused by a rupture of mediastinal
      neoplasms. We herein report a 70-year-old man who presented with mediastinal
      parathyroid adenoma manifested by the sudden onset of mediastinal bleeding.
      Preoperatively, he showed no symptoms or complications associated with
      hypercalcemia. No particular findings were found in the thorax except for a small
      nodule in the upper mediastinum. The nodule was resected through a collar
      incision, and pathohistology showed a parathyroid adenoma, with an intracapsular
      hemorrhage.

PMID- 12203061
TI  - Acute respiratory failure caused by an incarcerated right-sided adult bochdalek
      hernia: report of a case.
AB  - We herein report the case of a 63-year-old woman with a right-sided Bochdalek
      hernia. She was admitted to our hospital as an emergency patient with dyspnea and
      abdominal pain. A blood gas analysis showed hypoxia. A chest X-ray and computed
      tomography revealed a remarkable right diaphragm elevation caused by a herniation
      of the colon and right kidney. Under a thoracolaparotomy, a herniation of the
      strangulated colon and right kidney was recognized in the site of the foramen of
      Bochdalek, and a direct closure of the hernia opening was thus performed after
      repairing the location of the colon and right kidney. A right-sided Bochdalek
      hernia in adults is a rare clinical entity and there have been fewer than ten
      such cases so far reported in the world literature. This case highlights the need
      for a prompt diagnosis and appropriate surgical intervention.

PMID- 12203062
TI  - Successful management and outcome of a postoperative aortogastric fistula in a
      patient with recurrent gastric cancer: report of a case.
AB  - The case of a 57-year-old patient is described, who presented with regional
      gastric cancer recurrence 1 year after a gastrectomy for a T3N1M0 (Stage IIIA)
      adenocarcinoma of the stomach. He underwent a radical resection with
      intraoperative radiation to the regional field. Two months postoperatively,
      massive upper gastrointestinal bleeding occurred. Operative management included a
      left thoracotomy, aortic cross-clamping, laparotomy, and suture repair of a
      fistula from the root of the celiac trunk to the gastric remnant, with a
      completion gastrectomy. The patient survived and underwent a delayed
      reconstruction and closure. Subsequently, several repeat bleeding episodes took
      place, from sources including the celiac, common hepatic, and proper hepatic
      arteries. Multiple angiographic coil embolization and surgical procedures became
      necessary, ultimately requiring an esophagostomy and cecostomy for intestinal
      diversion. A rectus abdominis flap coverage of the exposed large arteries was
      performed. Although two more bleeding episodes took place, the patient was
      ultimately managed successfully. He is currently free of disease 3 years after
      reexploration, able to take oral nutrition, with intermittent jejunostomy feeding
      supplements. The discussion highlights aspects relevant to this case: the
      importance of a complete regional resection during a gastric cancer resection,
      the management strategy for an acute catastrophic intra-abdominal bleeding, and
      possible mechanisms that could contribute to such bleeding, including
      intraoperative radiation and postoperative infection.

PMID- 12203063
TI  - Laparoscopic wedge resection for gastric perforation after endoscopic mucosal
      resection: report of a case.
AB  - We performed laparoscopic wedge resection to treat gastric perforation that
      occurred as a complication of endoscopic mucosal resection (EMR) in a 53-year-old
      man. We believe this is an appropriate procedure to treat gastric perforation
      after EMR for early gastric cancer because it is safe and minimally invasive, and
      faster recovery can be expected than after conservative therapy.

PMID- 12203064
TI  - Reconstruction of a large duodenal defect created by resection of a duodenal
      tubulovillous adenoma using a double-tract anastomosis to a retrocolic roux-en-y
      loop: report of a case.
AB  - Adenomas arising in the duodenum are uncommon. The surgical approach to adenoma
      of the duodenum remains controversial. We herein report the successful closure of
      a large defect after a partial duodenectomy for an adenoma. A 60-year-old man
      developed duodenal adenoma. An upper gastrointestinal roentgenographic series and
      endoscopy revealed a 2.5-cm tumor located adjacent to the duodenal papilla. The
      tumor was too large to be removed endoscopically, and therefore it was resected
      en bloc by a partial duodenectomy. Histology confirmed the diagnosis of benign
      tubulovillous adenoma. The large duodenal defect created by resection of the
      tumor was closed with double-tract anastomosis to a retrocolic Roux-en-Y loop.
      Large duodenal defects represent difficult surgical problems. Closure by direct
      anastomosis to a Roux-en-Y loop side-to-side is thus considered to be the
      procedure of choice.

PMID- 12203065
TI  - Juvenile polyps in the small intestine presenting as jejunojejunal
      intussusception in a 10-year-old child: report of a case.
AB  - We report herein the case of a 10-year-old child with small bowel obstruction
      caused by jejunojejunal intussusception of a juvenile polyp. To the best of our
      knowledge, this is only the third case reported of a juvenile polyp in the small
      intestine and the first case to be documented in the English literature.

PMID- 12203066
TI  - Primary malignant melanoma of the small intestine: report of a case.
AB  - The small intestine is the most common site of gastrointestinal (GI) metastases
      from cutaneous malignant melanoma; however, primary malignant melanoma
      originating in the small intestine is extremely rare. We report the case of a 72
      year-old man found to have a primary malignant melanoma in the ileum. The patient
      presented with anorexia, weight loss, diffuse colicky abdominal pain, and
      episodic rectal bleeding. A preoperative diagnosis of a small intestinal tumor
      was based on the findings of enteroclysis and computed tomography scanning. This
      diagnosis was confirmed at laparotomy and an enterectomy was performed.
      Histopathological examination of the resected specimen clarified the exact nature
      of the lesion, confirming the diagnosis of melanoma. A thorough postoperative
      investigation did not reveal a primary lesion in the skin, anus, oculus, or any
      other location. Thus, we diagnosed this tumor as a primary lesion. One year after
      his operation, the patient remains well without any evidence of recurrence.
      Primary malignant melanoma of the small intestine is an extremely rare lesion,
      which must be differentiated from other intestinal tumors.

PMID- 12203067
TI  - Incarceration of small bowel herniation through a defect of the broad ligament of
      the uterus: report of a case.
AB  - Intestinal herniation through a defect in the broad ligament of the uterus is
      uncommon among internal herniations. We herein report a 59-year-old woman with
      intestinal obstruction, who had no previous history of surgical treatment except
      for an appendectomy. The laparotomy revealed an incarceration of the small bowel
      herniation through the defect of the right broad ligament. This possibility
      should therefore be considered in the differential diagnosis for female patients
      presenting with an intestinal obstruction without any history of a prior
      laparotomy.

PMID- 12203068
TI  - An unusual perforation of the colon: report of two cases.
AB  - We herein present two cases of a colorectal perforation due to uncommon reasons.
      First, we treated a 45-year-old woman for a stercoral perforation of the sigmoid
      colon. The pathognomonic etiology was a barium fecaloma originating from an upper
      gastrointestinal series 9 months before admission. The second case was a 46-year
      old woman who was admitted with a perforation of the transverse colon. She had
      experienced perforations of the sigmoid colon at 32 years of age and of the
      rectum at 44 years of age, respectively. The second and third conditions were
      diagnosed to be idiopathic, and were histologically proven by an abrupt
      obliteration and a thinness of the colonic wall with some infiltration of
      inflammatory cells. The first condition, however, was most likely a stercoral
      perforation. The postoperative course of these patients was uneventful, and both
      are doing well at this writing.

PMID- 12203069
TI  - Laparoscopic cholecystectomy after coronary artery bypass grafting using the
      right gastroepiploic artery: report of a case.
AB  - A laparoscopic cholecystectomy (LC) was successfully performed on a 61-year-old
      man who had undergone coronary artery bypass grafting (CABG) using the right
      gastroepiploic artery (RGEA). He complained of right hypochondralgia 20 days
      after CABG. Gallstones were diagnosed and a cholecystectomy was performed 9
      months after CABG. Under general anesthesia, the operation was performed using a
      pneumoperitonium. When a laparoscope was inserted, the RGEA pedicle could be
      clearly recognized. The pedicle obstructed the operating field and made the
      working space narrower than usual. No ST changes on the electrocardiogram were
      seen during LC, especially during the initiation of pneumoperitonium, the
      insertion of the ports, or when retracting the gallbladder. The postoperative
      course was uneventful. To avoid complications, care should be taken not to
      stretch the RGEA pedicle during LC, and careful monitoring of the
      electrocardiogram is also necessary. It is difficult to view the operating field
      and the RGEA pedicle together. It is therefore better to insert another
      laparoscope for concomitant monitoring of the RGEA pedicle.

PMID- 12203070
TI  - Spontaneous regression of a metastatic liver tumor: report of a case.
AB  - A 60-year-old man, who suffered from advanced rectal cancer accompanied with
      liver metastasis, underwent an abdominoperineal resection and a partial
      hepatectomy. He remained well until 4 months after surgery when he developed a
      biopsy-proven recurrent intrapelvic mass and multiple liver tumors. At 6 months
      after surgery, the metastatic liver tumors grew larger and almost completely
      occupied both lobes of the liver. However, 9 months after surgery, the liver
      tumors regressed remarkably and his clinical condition improved without any
      specific treatment for cancer. Although he died of cancerous peritonitis 18
      months after surgery, the autopsy findings did not indicate any apparent regrowth
      of the liver tumors. To date, only one case report of a spontaneous regression of
      a metastatic liver tumor from colorectal cancer has been published in the English
      literature. We herein describe this rare case and discuss some of the reasons
      potentially responsible for the regression.

PMID- 12203071
TI  - Retroperitoneal schwannoma misdiagnosed as a psoas abscess: report of a case.
AB  - A retroperitoneal cystic mass compressing the right psoas muscle was found
      incidentally by ultrasonography in a 67-year-old woman. The radiological findings
      and a history of costal caries led us to suspect a psoas cold abscess. Ultrasound
      guided needle aspiration was done to establish the diagnosis and to drain the
      content, but only a small amount of sterile fluid was obtained. The patient
      complained of neuralgia in her right leg at the time of puncture. Under the
      preoperative diagnosis of a neurogenic tumor, the mass was surgically resected,
      and found to be filled with old blood. The solid region consisted of a
      proliferation of fusiform cells, leading to a diagnosis of benign schwannoma.
      Retroperitoneal schwannoma is often misdiagnosed as an adjacent anatomical
      structure. Thus, we conclude that both microbiological and cytological
      examination of an aspiration specimen is important when psoas abscess is
      considered in a differential diagnosis.

PMID- 12203072
TI  - Enteric nervous plasticity and development: dependence on neurotrophic factors.
AB  - The enteric nervous system in the mammalian gut is histologically and to some
      extent functionally similar to the central nervous system. Thus, structural and
      functional similarities between these systems are evident. As shown for the
      central nervous system, differentiation of neural crest-derived precursor cells
      of the enteric nervous system also depends essentially on different neurotrophic
      factors. Moreover, recent studies have revealed that these trophic factors also
      play a critical role throughout life by regulating neurotransmitter and
      neuropeptide synthesis, and by influencing neuronal morphology and synaptic
      functions. Consequently, our understanding of these complex interactions of the
      enteric nervous system and neurotrophic factors requires synergistic efforts from
      neurophysiology, biochemistry, and pharmacology in order to understand the
      complex phenomena of enteric nervous development and plasticity in the gut.
      Knowledge of these mechanisms might help to develop strategies for therapy of
      neuronal abnormalities, which cause different gastrointestinal diseases.

PMID- 12203073
TI  - Influence of Helicobacter pylori infection on in vitro responsiveness of gastric
      fundus to agonists and to stimulation of enteric nerves in Mongolian gerbils.
AB  - BACKGROUND: It has recently been proposed that disturbed gastric adaptive
      relaxation may play a role in functional dyspepsia (FD). However, the effect of
      Helicobacter pylori infection, which may be one of multiple factors associated
      with FD, on gastric relaxation is not clear. The aim of this study was to clarify
      the influence of H. pylori infection on the responsiveness of smooth muscles of
      the gastric fundus to agonists or to stimulation of enteric nerves, with
      particular emphasis on nonadrenergic noncholinergic (NANC) relaxation. METHODS:
      We investigated myogenic responses to carbachol (CCH) and sodium nitroprusside
      (SNP), and neural responses to electrical field stimulation (EFS), in the absence
      or presence of atropine and guanethidine, in the tissues of the gastric fundus of
      H. pylori-infected Mongolian gerbils (MGs). RESULTS: H. pylori-infected MGs
      showed typical gastritis, with H. pylori colonization in the antrum and body. The
      gastric fundus adjacent to the body was composed of thin gastric mucosa with mild
      inflammation, which was covered with stratified squamous epithelium, and the
      muscle layer communicated with that of the gastric body. In the gastric fundus,
      CCH- and SNP-induced responses were not different in controls and H. pylori
      infected MGs. In the absence of any antagonists, EFS-evoked contraction tended to
      be reduced in H. pylori-infected MGs compared with that in control MGs, albeit
      that the difference was statistically nonsignificant. N(omega)-nitro- l-arginine
      methyl ester inhibited NANC relaxation in the tissues in both groups. EFS-evoked
      NANC relaxation remained intact in H. pylori-infected MGs. CONCLUSIONS: Mild
      inflammation in gastric fundus associated with H. pylori infection does not cause
      enteric neuromuscular dysfunction of the site in vitro.

PMID- 12203074
TI  - Comparison of recovery of gastric phase III motility and gastric juice output
      after different types of gastrointestinal reconstruction following pylorus
      preserving pancreatoduodenectomy.
AB  - BACKGROUND: Early gastric stasis is a frequent complication of pylorus-preserving
      pancreatoduodenectomy (PPPD). However, few reports have addressed this phenomenon
      in relation to the type of gastrointestinal reconstruction. We compared
      gastrointestinal motility and gastric juice output after two different types of
      gastrointestinal reconstruction following PPPD, end-to-side duodenojejunostomy
      after pancreaticojejunostomy and hepaticojejunostomy (group 1) and end-to-end
      duodenojejunostomy before pancreaticojejunostomy and hepaticojejunostomy (group
      2). METHOD: In a total of 25 patients, 10 in group 1 and 15 in group 2, who
      underwent PPPD, manometry was repeated to assess gastric and jejunal motility
      until the first occurrence of phase III activity of gastric cyclic motor activity
      (CMA). The plasma level of motilin was measured in each phase of the gastric CMA
      and compared between the two groups. The daily volume of gastric juice output
      through a gastrostomy tube was also recorded for comparison. RESULT: There was no
      significant difference in the time period for recovery of gastric phase III
      activity and gastric juice output between the two groups. However, abnormal
      contractions with an increased basal pressure appeared frequently in the afferent
      jejunal loop only in group 1. The plasma motilin level after PPPD showed no
      apparent cyclic change even after the recovery of gastric phase III in either
      group. CONCLUSION: Gastrointestinal reconstructive procedures have almost no
      effect on the recovery of gastric CMA. The plasma motilin concentration does not
      play a major role in the recovery of gastric CMA in the early postoperative
      period after PPPD.

PMID- 12203075
TI  - Color Doppler findings of gastric varices compared with findings on computed
      tomography.
AB  - BACKGROUND: The aim of this study was to evaluate the hemodynamics of gastric
      varices. METHODS: We evaluated the detection rates of gastric varices, inflowing
      vessels to gastric varices, and outflowing vessels from gastric varices in 24
      patients with gastric varices, using color Doppler sonography, and compared these
      findings with computed tomography findings. Eighteen patients had F2-type varices
      and 6 had F3-type, classified according to the Japanese Research Society for
      Portal Hypertension. Fourteen patients had fundal varices, and 10 had cardiac and
      fundal varices. RESULTS: The detection rates of collateral veins using color
      Doppler sonography were as follows: gastric varices were detected in all 24
      patients (100%); inflowing vessels, in 21 of the 24 patients (87.5%); and
      outflowing vessels, in 18 of the 24 patients (75.0%). The detection rates of
      collateral veins, using computed tomography, were: gastric varices were detected
      in all 24 patients (100%); inflowing vessels, in all 24 patients (100%); and
      outflowing vessels, in 21 of the 24 patients (87.5%). The color Doppler findings
      agreed perfectly with the computed tomography findings in 13 of the 24 patients
      (54.2%). CONCLUSIONS: Although color Doppler sonography is a useful, noninvasive
      modality for evaluating the hemodynamics of gastric varices, it falls short in
      visualizing the detailed hemodynamics of the inflowing and outflowing vessels of
      gastric varices in half of the patients when compared with computed tomography.

PMID- 12203076
TI  - Simultaneous anus and bowel operation is preferable for anal fistula in Crohn's
      disease.
AB  - BACKGROUND: Anal fistula in Crohn's disease is reportedly intractable, and little
      is known about factors influencing the outcome of surgery. The purpose of this
      study was to clarify the current status of surgery for anal fistula in Crohn's
      disease, and possible factors influencing surgical outcome were investigated.
      METHODS: From August 1993 to September 1998, 39 of 239 Crohn's disease patients
      underwent long-term seton drainage. The patients were divided into two groups:
      patients who received simultaneous bowel and anus operation (simultaneous group;
      n = 11) and a control group ( n = 28). RESULTS: Twenty-nine of the 39 (74%)
      patients received two seton drains or more, with a mean of 2.7. Twenty-one (54%)
      patients received two or more operations. The rate of seton drain removal was 52%
      at 12 months after operation and 86% at 24 months. The cumulative rate of seton
      drains remaining at 12 months after the first operation was 10% in the
      simultaneous group and 37.7% in the control group, with a significant difference
      ( P = 0.038). Multivariate analysis revealed that simultaneous operation was the
      only significant factor that influenced the surgical results ( P = 0.0489). Seven
      of the 21 (33%) patients recurred after total removal of seton drain(s). All the
      patients who had recurrence belonged to the control group. Continence did not
      deteriorate after seton drainage. Ten patients (26%) required enterostomy and no
      patient received proctectomy. CONCLUSIONS: Healing of Crohn's anal fistula was
      significantly better in the simultaneous group than in the control group, and the
      recurrence rate was lower in the simultaneous group. Seton drainage for anal
      fistula in Crohn's disease was effective and preserved sphincter function.

PMID- 12203077
TI  - Clinical features of liver disturbance in rheumatoid diseases:
      clinicopathological study with special reference to the cause of liver
      disturbance.
AB  - BACKGROUND: Liver disturbance in rheumatoid diseases results not only from liver
      disease associated with the rheumatoid diseases themselves but also from various
      other causes. This study aimed to elucidate the clinical features of liver
      disturbance in rheumatoid diseases, focusing on the cause of this disturbance.
      METHODS: A clinicopathological study was performed in 306 patients (106 with
      systemic lupus erythematosus, 71 with Sjogren's syndrome, 59 with rheumatoid
      arthritis, 27 with scleroderma, 30 with polymyositis, and 13 with polyarteritis
      nodosa). RESULTS: Liver disturbance occurred in 43% of these patients and
      resulted from various causes. Its degree and duration varied from one cause to
      another. Liver disease associated with rheumatoid diseases was the leading cause
      of the liver disturbance in these patients and was characterized by mild and
      transient liver disturbance (maximum alanine aminotransferase [ALT] level during
      the study period, 68 +/- 8 IU/ml; maximum alkaline phosphatase [ALP] level, 410
      +/- 31 IU/ml; duration of liver disturbance, 6 +/- 2 months). Most patients with
      this type of liver disease showed minimal change in liver histology, although two
      thirds of those evaluated by the international scoring system for autoimmune
      hepatitis (AIH) were classified as "probable" or "definite". Eight of 14 patients
      with histologically proven chronic hepatitis or cirrhosis were infected with
      hepatotropic virus (7 with hepatitis C virus [HCV] and 1 with hepatitis B virus
      [HBV]). Five of 9 patients in whom the hepatic lesion progressed had hepatotropic
      virus infection (4 with HCV and 1 with HBV), and the other 4 patients suffered
      from autoimmune liver diseases. CONCLUSIONS: Liver disease associated with
      rheumatoid diseases was the leading cause of liver disturbance in these patients
      and was characterized by mild and transient liver disturbance, whereas
      progressive liver diseases were often associated with hepatotropic virus, mainly
      HCV, or autoimmune liver diseases. Liver histology is indispensable for
      differentiating AIH from liver disease associated with rheumatoid diseases.

PMID- 12203078
TI  - Decreasing serum alpha-fetoprotein levels in predicting poor prognosis of acute
      hepatic failure in patients with chronic hepatitis B.
AB  - BACKGROUND: We carried out a study to predict the prognosis of acute hepatic
      failure in patients with chronic hepatitis B. METHODS: We studied 25 consecutive
      patients with severe acute hepatitis. Severe acute hepatitis was defined as the
      development of acute hepatitis with a total serum bilirubin level of more than 15
      mg/dl, prolonged prothrombin time (PT) of more than 5 s, and hepatic
      encephalopathy (HE). All patients were assessed for King's criteria. Positivity
      for King's criteria was defined as PT more than 100 s, or any three of the
      following: (age < 10 years or >40 years; cryptogenic or drug-induced hepatitis;
      jaundice for more than 7 days before the onset of HE; PT > 50 s; and serum
      bilirubin > 17.5 mg/dl). All but 1 patient had serial serum alpha-fetoprotein
      (AFP) levels measured every 1-2 weeks. RESULTS: Eleven of 17 patients who died
      during the study met the King's criteria, whereas none of the surviving patients
      met the criteria. The sensitivity was 64.7% and the specificity, 100% for King's
      criteria in predicting a poor prognosis. In 16 of the 17 deceased patients, the
      AFP levels were reduced while their jaundice increased (sensitivity, 94.1%;
      specificity, 87.5%). All 17 deceased patients met the King's criteria and/or had
      reduced AFP levels while their jaundice increased (sensitivity, 100%;
      specificity, 87.5%). CONCLUSIONS: Our observations suggest that the combined use
      of follow-up AFP levels and King's criteria is helpful in predicting the poor
      prognosis of severe acute hepatitis superimposed on chronic hepatitis B.

PMID- 12203079
TI  - The time course of gap-junctional protein connexin 32 expression in the pancreas
      after the induction of acute pancreatitis by caerulein in rats.
AB  - BACKGROUND: We previously demonstrated that the immunostaining of the gap
      junction protein, connexin 32 (Cx 32), in the pancreas was markedly reduced in
      caerulein (Cn)-induced acute pancreatitis. The expression of Cx 32 in the
      pancreas during the course of acute pancreatitis is unclear. To address this, we
      examined Cx 32 mRNA and protein expression in the pancreas. METHODS: Cx 32 mRNA
      and protein expression in the pancreas was examined by Northern blot analysis and
      Western blot analysis, respectively, 1, 4, 7, and 14 days after the induction of
      acute pancreatitis. RESULTS: Cx 32 mRNA was identified in normal rat pancreas,
      and the value for the relative intensity against 18S rRNA was 0.57 +/- 0.15 (mean
      +/- SD). After the induction of acute pancreatitis by caerulein, the Cx 32 mRNA
      expression levels were increased on day 1, day 4, day 7, and day 14 compared with
      levels in the normal pancreas (1.63-fold, 1.61-fold, 1.49-fold, and 1.35-fold,
      respectively). A significant increase in Cx 32 protein expression was detected on
      day 1 and day 4 (1.67 +/- 0.15-fold and 1.72 +/- 0.2-fold, respectively), while
      Cx 32-positive spots, determined by immunohistochemical analysis, were markedly
      decreased on day 1 and had returned to normal by day 14. CONCLUSIONS: These
      results show that the expression of Cx 32 increases early on after the induction
      of pancreatitis by Cn, and that the normalization of Cx 32-immunostained spots in
      Cn-induced acute pancreatitis occurs after the increase in Cx 32 mRNA and protein
      expression.

PMID- 12203080
TI  - Superior mesenteric artery syndrome: diagnosis and treatment from the
      gastroenterologist's view.
AB  - BACKGROUND: Superior mesenteric artery syndrome (SMAS) is caused by compression
      of the third part of the duodenum between the superior mesenteric artery and the
      aorta. It occurs most frequently in patients with rapid weight loss. METHODS: We
      report two young patients, who each presented with a longstanding history of
      postprandial abdominal pain, nausea, and voluminous vomiting. The diagnosis of
      SMAS was established by digital fluoroscopy and contrast-enhanced spiral computed
      tomography (CT) scan. The findings obtained by endoscopic ultrasound (EUS) at the
      site of duodenal compression, using a miniprobe, were of substantial diagnostic
      value and in good agreement with the radiological observations. RESULTS: Both
      patients, once diagnosed, were treated conservatively by providing enteral or
      parenteral high caloric nutrition. Weight gain was accompanied by the complete
      relief of symptoms. CONCLUSIONS: Pathogenesis, diagnostic procedures, and therapy
      are reviewed in order to draw attention to this rare entity.

PMID- 12203081
TI  - Esophageal intramural pseudodiverticulosis (diffuse type).
AB  - A rare case of esophageal intramural pseudodiverticulosis (EIPD) in a 65-year-old
      woman with intermittent dysphagia is reported. An upper gastrointestinal series
      revealed multiple pseudodiverticula, which had tiny flask-shaped outpouchings
      with a narrow neck extending outward from the upper to the lower thoracic
      esophageal wall. In particular, the occurrence of the pseudodiverticula was
      coincident with a narrowed segment of inflamed esophagus. The length of the
      esophagus involved was approximately 15 cm. Endoscopic findings included mild
      stricture and chronic inflammation of the mucosa. Biopsy specimens showed active
      chronic esophagitis with bacterial and Candida superinfection, but no evidence of
      neoplasm. Cellular local immune reactions, as a consequence of chronic
      inflammation, and possibly abnormal motor activity in the narrowed esophagus, may
      explain the etiological agent or may be possible secondary factors that caused
      the EIPD.

PMID- 12203082
TI  - A hyperdynamic portal syndrome with ascites after endoscopic laser treatment.
AB  - Laser therapy has gained wide acceptance and application in many medical
      disciplines. Side effects of laser therapy are rare and the most frequent mainly
      involve the skin. We describe a patient affected by familial adenomatous
      polyposis that had been repeatedly controlled and treated endoscopically using an
      Nd:Yag laser. He presented with a progressive hyperdynamic portal syndrome with
      ascites caused by some arterovenous fistulas. We hypothesize that a rare side
      effect of the laser treatment may have caused ischemic and coagulative tissue
      inflammation that triggered off the pathological communications between the
      arterial and portal circulation.

PMID- 12203083
TI  - Chronic intestinal pseudoobstruction ileus in a patient with rheumatoid
      arthritis: outcome of a stoma construction and its histopathological features.
AB  - We report the first case of a chronic intestinal pseudoobstruction (CIPO) in a
      patient with rheumatoid arthritis (RA) in whom a stoma was constructed at the
      sigmoid colon to decompress intracolonic pressure. The treatment improved quality
      of life in this patient, suggesting that surgical resection of the colon to
      decompress intracolonic pressure would be one of the options for the treatment of
      intractable CIPO. The resected specimen obtained from the sigmoid colon was found
      to be palisaded, with nuclei crowded in some areas of the inner circular muscle
      layer and thickened, with zonal or focal myxoid regions with interstitial
      fibrosis, composed of collagenous and elastic fibers, in the outer longitudinal
      muscle layer. Some of the smooth muscle cells in the outer longitudinal muscle
      layer showed mild degeneration with cytoplasmic vacuolar changes, but no
      inflammatory changes. However, further studies are required to determine whether
      these histopathological changes are unique to RA.

PMID- 12203084
TI  - Postpartum acute exacerbation of chronic hepatitis C with complete response to
      interferon-alpha.
AB  - We describe a patient with chronic hepatitis C who had severe postpartum acute
      exacerbation of the disease, with marked aminotransferase elevations and
      jaundice. The viral genotype was 2a, and the patient had a low viral load.
      Neither superinfection with another hepatotropic virus nor autoantibodies were
      evident. Markedly increased serum concentrations of T-helper (Th) 1-type
      cytokines and cytokine receptors, including interleukin (IL)-8, tumor necrosis
      factor (TNF)-alpha, soluble TNF receptor (sTNFR)-p55, sTNFR-p75, and soluble Fas
      antigen (sFas), as well as that of the Th 2-type cytokine, IL-10, were present.
      Complete biochemical and virologic response was achieved with interferon (IFN)
      alpha treatment, which decreased cytokine elevations while favoring Th 1
      dominance. Acute exacerbation of hepatitis C may occur when cellular immune
      responses are activated, as in late pregnancy and in the postpartum period.
      Treating such acute exacerbations immediately with IFN may be highly efficacious.

PMID- 12203085
TI  - Development of multicentric hepatocellular carcinoma after completion of
      interferon therapy.
AB  - We report a case of multicentric hepatocellular carcinoma that developed in a 74
      year-old man 3 and 6 years after interferon (IFN) treatment for chronic hepatitis
      C, despite sustained virologic, biochemical, and histological improvement.
      Initially, serum hepatitis C virus RNA was positive and the patients' serum level
      of alanine aminotransferase (ALT; 82 IU/ml) was abnormal. Hepatitis B virus (HBV)
      in the serum was negative for surface antigen, surface antibody, core antibody,
      and DNA. The patient was started on 10 x 10(6) international units (IU) of
      IFNalpha, 3 days a week for a total of 24 weeks. After the IFN therapy, the
      patient demonstrated a normal serum ALT level, and was continuously negative for
      HCV-RNA, and histology improved from chronic active hepatitis to chronic
      persistent hepatitis. Follow-up studies with ultrasonography (US) every 3 months
      and computed tomography (CT) every 6 months revealed no space-occupying lesion
      (SOL) for 3 years after IFN treatment.US-guided biopsies of two 15-mm hypoechoic
      SOLs in segments eight (S8) and seven (S7) 34 and 74 months, respectively, after
      IFN treatment showed well-differentiated hepatocellular carcinoma (HCC). Clinical
      data, imaging studies, and histologic examinations showed that both tumors were
      multicentric HCC. Further studies may provide insights into the possible role of
      HCV in hepatocarcinogenesis in patients demonstrating HCV eradication by IFN
      treatment.

PMID- 12203086
TI  - Serous cystadenoma of the pancreas associated with pancreas divisum.
AB  - Pancreas divisum is an embryologic anomaly of the pancreas that is characterized
      by a lack of fusion of the dorsal and ventral pancreatic ducts. It is rarely
      associated with pancreatic neoplasms. We report herein a rare association of
      pancreas divisum and serous cystadenoma of the pancreas. A 46-year-old Japanese
      woman presented with epigastralgia. Ultrasonography, computed tomography (CT) and
      magnetic resonance cholangiopancreatography revealed a multilocular cystic mass,
      measuring 7 cm in diameter, with a central stellate scar, in the body and tail of
      the pancreas. Angiography demonstrated a relatively hypervascular mass,
      suppressing the splenic vein. No arterial encasement was evident. Endoscopic
      retrograde pancreatography through the major papilla demonstrated only the duct
      of Wirsung; cannulation into the minor papilla was unsuccessful. In addition, CT
      showed a mildly dilated main pancreatic duct draining into the minor papilla.
      Distal pancreatectomy and splenectomy were performed, with the tentative
      diagnosis being serous cystic neoplasm of the pancreas, possibly malignant, and
      pancreas divisum. The cut surface of the resected specimen had a honeycomb-like
      appearance and the specimen consisted of multiple cysts of various sizes.
      Histopathological examination showed multiple cysts lined by a single layer of
      flat or cuboidal epithelial cells with glycogen in the cytoplasm. There was no
      evidence of malignancy. The histopathological diagnosis was serous cystadenoma of
      the pancreas. To the best of our knowledge, only three cases of serous
      cystadenoma of the pancreas associated with pancreas divisum have been reported.
      We report the fourth case of such an association, and briefly review the
      literature.

PMID- 12203087
TI  - Single administration of ecabet sodium diminishes the level of delta-13CO2 in
      urea breath test.

PMID- 12203088
TI  - Subserosal invading colon cancer with rare invasive form.

PMID- 12203089
TI  - Is color Doppler ultrasonography useful for the detection of gastric varices?

PMID- 12203090
TI  - Is AFP a new reliable marker of liver regeneration in acute hepatic failure?

PMID- 12203091
TI  - Isolation of connective-tissue-specific genes involved in Xenopus intestinal
      remodeling: thyroid hormone up-regulates Tolloid/BMP-1 expression.
AB  - To clarify connective-tissue-specific genes involved in adult epithelial
      development during amphibian intestinal remodeling, we have isolated 16 cDNA
      clones derived from the anterior part of Xenopus laevis intestine cultured in
      vitro by using subtractive suppression hybridization. Among four genes
      identified, the expression of Xtld, a Xenopus homolog of Drosophila Tolloid
      closely related to bone morphogenic protein-1 (BMP-1), was most remarkably up
      regulated during metamorphosis. To further explore the roles of Xtld in
      intestinal remodeling, we examined its developmental expression in the X. laevis
      intestine by in situ hybridization and northern blot analysis. Xtld mRNA first
      became detectable in the connective tissue just before the appearance of adult
      epithelial primordia. Subsequently, the level of Xtld mRNA reached a high in the
      connective tissue, concomitantly with adult epithelial development along the
      anteroposterior axis of the intestine. Thereafter, towards the completion of
      metamorphosis, the expression of Xtld mRNA was down-regulated. Thus, the
      expression profile of Xtld mRNA spatiotemporally correlates well with adult
      epithelial development in vivo. Furthermore, the present culture study has shown
      that thyroid hormone (TH) up-regulates the expression of Xtld mRNA organ
      autonomously in the anterior part of the intestine, but not in its posterior
      part, and that TH up-regulation of Xtld expression is not mediated by the
      epithelium. These results suggest that TH directly up-regulates Xtld expression
      in the connective tissue along the anteroposterior axis, which in turn plays
      important roles in adult epithelial development during amphibian intestinal
      remodeling.

PMID- 12203092
TI  - The body margin of the planarian Dugesia japonica: characterization by the
      expression of an intermediate filament gene.
AB  - We have cloned and sequenced a cDNA encoding an intermediate filament protein
      (IF) from the planarian Dugesia japonica named DjIFb. The deduced amino acid
      sequence of DjIFb has similarity to those of protostomic IFs and lamins,
      supporting a previous hypothesis that the protostomic IFs, including DjIFb, are
      evolutionarily closer to lamins than to vertebrate cytoplasmic IFs. In addition,
      analysis of the exon/intron organization revealed that 8 out of 10 introns of
      DjIFb were coincident in their position, even in the codon phase, with those of
      the non-neuronal IF of the snail Helix aspersa. This suggests that the
      Platyhelminthes are not the most primitive Bilateria but instead are
      evolutionarily close to the Mollusca. The DjIFb gene was expressed in particular
      cells, probably a kind of adhesive gland cell, which were present in the marginal
      region encircling the planarian body. The localization of DjIFb protein suggests
      that it plays an important role in the secretion of an adhesive substance. The
      specific expression pattern of the DjIFb gene enabled us to monitor how the body
      margin forms during planarian regeneration.

PMID- 12203093
TI  - Mesodermal and axial determinants contribute to mesoderm regionalization in Bufo
      arenarum embryos.
AB  - The existence of mesodermal determinants in the equator of Bufo arenarum embryos
      has been previously demonstrated. In this work, their role in dorso-ventral
      regionalization of mesoderm was studied by transferring the determinants to
      animal blastomeres. The transfer was performed by cleavage reorientation and
      cytoplasmic microinjection. Forced inclination during early cleavage caused
      deviation of the third cleavage plane and annexation of equatorial cytoplasm into
      animal quartets. Animal blastomeres from embryos oriented with the dorsal side
      up, incorporated ventro-equatorial cytoplasm and formed blood cells, mesenchyme,
      and coelomic epithelium. In contrast, animal blastomeres from embryos oriented
      with the ventral side up, acquired dorso-equatorial cytoplasm and developed
      notochord, somites, mesenchyme, coelomic epithelium and nervous tissue. In order
      to investigate if this dorso-ventral differentiation pattern responds to an
      interaction of mesodermal and axial factors, isolated 8-cell-stage animal
      quartets were microinjected with subcortical cytoplasm from: (a) the ventro
      equatorial region of synchronous embryos; (b) the vegetal pole of uncleaved eggs;
      (c) a combination of both cytoplasms. As expected, the implanted ventro
      equatorial cytoplasm promoted ventral mesoderm differentiation. Conversely, the
      joint transfer of ventro-equatorial cytoplasm and vegetal pole cytoplasm behaved
      as the dorso-equatorial cytoplasm, promoting dorso-lateral mesoderm and neural
      formation. Thus, mesoderm regionalization in B. arenarum embryos seems to be
      caused by a concurrent action of both mesodermal and axial determinants.

PMID- 12203094
TI  - Expression patterns of an Otx2 and an Otx5 orthologue in the urodele Pleurodeles
      waltl: implications on the evolutionary relationships between the balancers and
      cement gland in amphibians.
AB  - We report the characterization of an Otx2 and an Otx5 orthologue in the urodele
      Pleurodeles waltl. These two genes, termed PwOtx2 and PwOtx5, share highly
      conserved expression domains with their gnathostome counterparts at tailbud
      stages, like the developing forebrain ( PwOtx2), or the embryonic eye and
      epiphysis ( PwOtx5). As in Xenopus laevis, both are also transcribed in the
      dorsal lip of the blastopore during gastrulation and in anterior parts of the
      neural plate during neurulation. In addition, PwOtx5 displays a prominent
      expression in the developing balancers and the lateral non-neural ectoderm during
      neurulation, from which they derive. By contrast, PwOtx2 expression remains
      undetectable in the balancers and their presumptive territory. These data suggest
      that PwOtx5, but not PwOtx2, may be involved in the differentiation and early
      specification of balancers. Comparisons of Otx5 expression patterns in P.
      waltland X. laevis embryos suggest that, as previously shown for Otx2, changes in
      the regulatory mechanisms controlling Otx5 early expression in the non-neural
      ectoderm may occur frequently among amphibians. These changes may be related to
      the rise of cement glands in anurans and of balancers in urodeles. This
      hypothesis could account for some similarities between the two organs, but does
      not support a homology relationship between them.

PMID- 12203095
TI  - Retinoic acid synthesis in the prevertebrate amphioxus involves retinol
      oxidation.
AB  - All- trans-retinoic acid (RA) contributes to the establishment of the anterior
      posterior (AP) axis in chordates. In vertebrates, all- trans-retinol is oxidized
      to RA by two oxidative steps. However, the controversy about the enzymes
      responsible for retinol oxidation (ADH vs RDH) and the fact that some candidates
      are absent in cephalochordates questioned retinol oxidation in this lineage.
      Retinoid quantitation has revealed that Branchiostoma floridae adults contain
      both retinol and retinoic acid as well as retinal, the intermediate in the
      metabolic pathway. Furthermore, our data show that the developmental effects of
      retinol treatment are comparable to those reported for RA. SEM analysis revealed
      mouth and gill slit aberrations due to a posteriorization effect, also visualized
      by changes in the beta-galactosidase pattern. Overall, these findings support the
      idea that amphioxus metabolizes endogenous retinol to retinoic acid and suggest a
      common oxidative pathway for RA in the chordate phylum.

PMID- 12203096
TI  - Developmental expression of a class IV POU gene in the gastropod Haliotis asinina
      supports a conserved role in sensory cell development in bilaterians.
AB  - POU-IV genes regulate neuronal development in a number of deuterostomes
      (chordates) and ecdysozoans (arthropods and nematodes). Currently their function
      and expression in the third bilaterian clade, the Lophotrochozoa, comprising
      molluscs, annelids and their affiliates, is unclear. Herein we characterise the
      developmental expression of HasPOU-IV in the gastropod mollusc, Haliotis asinina.
      The POU-IV gene is transiently expressed in 11 distinct larval territories during
      the first 3 days of development. HasPOU-IV is first expressed in sets of ventral
      epidermal cells in the newly hatched trochophore larvae. As larval morphogenesis
      proceeds, we observe HasPOU-IV transcripts in cells that putatively form a range
      of sensory systems including chemo- and mechanosensory cells in the foot,
      cephalic tentacles, the ctenidia, the geosensory statocyst and the eyes. By
      comparing HasPOU-IV expression with POU-IV genes in other bilaterians we infer
      that this class of POU-domain genes had an ancestral role in regulating sensory
      cell development.

PMID- 12203097
TI  - An efficient in situ hybridization protocol for multiple tissue sections and
      probes on miniaturized slides.
AB  - To facilitate detection of gene activity in tissue sections we combined common
      protocols of in situ hybridization on tissue sections (TSISH) with the technique
      of whole-mount in situ hybridization (WMISH). Miniature glass slides for mounting
      tissue sections were cut from regular microscope slides and handled for in situ
      hybridization in laboratory-made 2-ml containers (baskets) similar to those
      originally used for WMISH on Drosophila embryos. A salient point of the method is
      the use of airtight reaction vessels placed in a dry thermostat for critical
      hybridization steps as this facilitates reproducible and stringent hybridization
      conditions which are difficult to achieve on tissue sections otherwise. The
      practicability of the method is illustrated on consecutive serial frozen sections
      of murine neonatal cerebellum hybridized for math1 and neuroD, two
      developmentally regulated genes with distinct expression patterns. For both genes
      excellent spatial resolution and a highly dynamic range of signal intensity was
      obtained. The approach enables simple processing of multiple probes, allows the
      efficient and economic use of small tissue samples and is amenable to automation.

PMID- 12203098
TI  - A phase I study of the GM-CSF antagonist E21R.
AB  - PURPOSE: E21R is a competitive inhibitor of GM-CSF. This is the initial clinical
      study to investigate the safety, toxicity and pharmacokinetics of escalating
      doses of E21R. PATIENTS AND METHODS: Cohorts of three patients received doses of
      10, 30, 100, 300, 600 and 1000 micro g/kg per day given subcutaneously daily for
      10 days. Eligible patients had solid tumours known to express GM-CSF receptors
      (breast, prostate, colon and lung cancer, and melanoma). No bone marrow
      involvement or concomitant steroids were permitted. A total of 22 patients
      received doses ranging from 10 to 1000 micro g/kg per day. There were 18 males
      and 4 females with a median age of 60 years (range 33 to 81 years). Eight
      patients had an ECOG performance status of 0, seven a performance status of 1,
      and seven a performance status of 2. There were ten patients with colon cancer,
      four with prostate cancer, three with lung cancer, three with melanoma and two
      with breast cancer. RESULTS: E21R was in general well tolerated and the maximum
      tolerated dose was not reached. The most severe toxicities were WHO grade 3
      injection site erythema in one patient and grade 2 in two patients, grade 2
      lethargy in three patients and grade 2 muscle aches and soreness, grade 2 joint
      pains and grade 2 thirst in one patient each. The primary pharmacokinetic
      parameters were dose-independent. Dose-dependent transient eosinophilia was noted
      from day 3. A fall in PSA levels was recorded in two patients with prostate
      cancer during their initial cycles of E21R, but they subsequently rose again.
      Serum from patients treated at 600 and 1000 micro g/kg per day antagonized GM-CSF
      mediated TF-1 cell proliferation in vitro. CONCLUSION: E21R can be safely given
      at doses up to 1000 micro g/kg per day.

PMID- 12203099
TI  - Phase I and pharmacokinetic study of vinblastine and high-dose megestrol acetate.
AB  - PURPOSE: Preclinical data indicate that progestational agents (progesterone,
      medroxyprogesterone acetate and megestrol acetate) interact with p-glycoprotein
      (P-gp) and reverse P-gp-associated resistance to vinca alkaloids and other
      natural products. Based on these data, we performed a phase I study of high-dose
      oral megestrol acetate and vinblastine to evaluate the safety of this regimen.
      PATIENTS AND METHODS: Enrolled in the study were 61 patients with advanced solid
      tumors, refractory to standard therapy. Cohorts of patients received megestrol
      acetate according to the following escalation scheme (loading dose/maintenance
      dose, twice daily for 7 days): 750 mg/250 mg, 750 mg/375 mg, 1000 mg/500 mg, 1500
      mg/1000 mg, 3000 mg/2000 mg, 4500 mg/3000 mg, 6000 mg/4000 mg, and 7500 mg/5000
      mg. They also received 1.5 mg/m(2) per day of vinblastine by continuous infusion
      for 5 days (days 2 to 6). RESULTS: Of the 61 patients, 59 were evaluable for
      toxicity. A maximum tolerated dose (MTD) was not reached. The regimen was well
      tolerated. Of the 59 patients, 10 (17%) experienced grade 4 leukopenia. All of
      these cases were at dose levels 3 to 8. There was an increase in the steady-state
      concentration (Css) of megestrol acetate with increasing dose up to the sixth
      dose level. Further increases in the dose produced no change in the megestrol
      acetate Css. Only 2.4% of megestrol acetate was free in the plasma as compared to
      65.6% in RPMI culture medium. Megestrol acetate administration was associated
      with profound suppression of ACTH and cortisol levels. CONCLUSIONS: The
      combination of vinblastine and megestrol acetate was well tolerated. An MTD for
      this combination was not achieved as a result of the saturable absorption of
      megestrol acetate. Although potentially therapeutic serum concentrations of
      megestrol acetate were achieved, it is unlikely that MDR was reversed given the
      high protein-binding of the drug. Profound suppression of the pituitary-adrenal
      axis was also observed during the administration of megestrol acetate.

PMID- 12203100
TI  - Potentiation of the antitumour effect of cyclophosphamide in mice by thalidomide.
AB  - PURPOSE: Thalidomide has recently shown significant promise in the treatment of
      some types of cancer, and trials in combination with conventional chemotherapy
      are being undertaken. We wished to determine whether thalidomide potentiated the
      effect of cyclophosphamide, a commonly used cytotoxic drug, in a murine tumour
      model. METHODS: C57Bl/6 mice implanted with subcutaneous Colon 38 tumours were
      treated with cyclophosphamide alone or together with thalidomide as a single
      intraperitoneal injection and tumour growth was measured. Concentrations of
      cyclophosphamide, 4-hydroxycyclophosphamide, 4-ketocyclophosphamide and 2
      dechloroethylcyclophosphamide were determined in plasma, liver and tumour tissue
      using coupled high-performance liquid chromatography-mass spectrometry at
      different times after treatment. RESULTS: Cyclophosphamide alone (220 mg/kg)
      induced growth delays of 11-13 days with no cures, whereas cyclophosphamide
      together with thalidomide (100 mg/kg) cured mice of their tumours. Thalidomide at
      lower doses (1-20 mg/kg) also potentiated the antitumour effect. Coadministration
      of thalidomide (100 mg/kg) dramatically decreased the clearance of
      cyclophosphamide and its metabolites from plasma and tissue, with corresponding
      increases in the area under the concentration-time curves. The magnitude of the
      effect was dependent on the dose of thalidomide over the range 1-20 mg/kg with no
      further effect at a dose of 100 mg/kg. CONCLUSIONS: Coadministration of
      thalidomide and cyclophosphamide gave markedly greater activity against Colon 38
      tumour compared with either drug alone. Investigation of the reason for this
      effect revealed thalidomide to possess the novel property of dramatically
      decreasing the clearance of cyclophosphamide and its metabolites.

PMID- 12203101
TI  - Mechanisms of the apoptotic activity of Cl-F-araA in a human T-ALL cell line,
      CCRF-CEM.
AB  - PURPOSE: The purpose of the present study was to characterize the mechanisms of
      the antitumor activity of 2-chloro-9-(2-deoxy-2-fluoro-beta- D
      arabinofuranosyl)adenine (Cl-F-araA) against lymphocytic leukemia. Recent
      evidence indicates that Cl-F-araA has more potent antitumor activity in vitro
      against human leukemia cell lines than against human solid tumor cell lines
      originating from different tissue. We analyzed the mechanism of action of Cl-F
      araA using a human T-acute lymphocytic leukemia cell line, CCRF-CEM, in vitro and
      in vivo. RESULTS: Cl-F-araA exhibited marked antitumor activity in vitro and in
      vivo, and this was correlated with its ability to induce apoptosis, particularly
      in vivo. To analyze the mechanisms of the apoptotic activity of Cl-F-araA, we
      sought to determine the effects of the drug on the levels of Bcl-2 family
      proteins (Bcl-2, Bcl-X(L), Mcl-1, Bax, Bak) and cell survival signals via Akt.
      Western blot analysis revealed that Cl-F-araA induced a dose- and time-dependent
      downregulation of Bcl-X(L) and Mcl-1 proteins, and a dose- and time-dependent
      dephosphorylation of Akt and its downstream effectors (Bad, FKHRL1), particularly
      in vivo. In addition, there was a marked increase in the population of cells in
      G(1)/S and early S phase. We therefore investigated the changes in the Cdc25A
      protein to characterize the mechanism involved in the G(1)/S accumulation. Cl-F
      araA induced a dose- and time-dependent downregulation of the Cdc25A protein
      whereas the Cdc25C protein remained unchanged. We further found that in
      combination with caffeine, Cl-F-araA potentiated apoptosis induction.
      CONCLUSIONS: Taken together, our findings suggest that Cl-F-araA may be an
      effective drug in vivo.

PMID- 12203102
TI  - In vitro and in vivo effects of repifermin (keratinocyte growth factor-2, KGF-2)
      on human carcinoma cells.
AB  - PURPOSE: Repifermin (keratinocyte growth factor-2, KGF-2) is a growth factor that
      selectively induces epithelial cell proliferation, differentiation and migration.
      The objective of this study was to assess the effect of repifermin on in vitro
      tumor cell proliferation and in vivo tumor growth using a variety of human
      carcinoma cell lines with differing growth rates and levels of KGF receptor
      (KGFR) expression. METHODS: Potential effects of repifermin on in vitro cell
      proliferation were evaluated by alamarBlue and/or [(3)H]-thymidine incorporation
      assays under a range of serum conditions. In vivo tumor growth was evaluated by
      implanting KGFR(+) carcinomas subcutaneously into nude mice and measuring tumor
      growth over time in mice injected intravenously (i.v.) or intraperitoneally
      (i.p.) with repifermin or placebo. RESULTS: In vitro, none of the 30 human
      carcinoma cell lines tested demonstrated a substantial increase in proliferation
      in response to repifermin over the concentration range 0.01 to 1000 ng/ml. In
      vivo results showed no significant tumor growth-promoting activity when single-
      or multiple-cycle intravenous injections of repifermin (1 mg/kg) were given to
      athymic nude mice inoculated with human KGFR(+) tumors of the pharynx (Detroit
      562, FaDu), colon (Caco-2), salivary gland (A-253) or tongue (SCC-25, CAL 27). In
      addition, repifermin (0.2 or 2 mg/kg) injected i.p. for 2 weeks had no effect on
      the growth of eight other human carcinomas including those of the ovary
      (NIH:OVCAR-3, SK-OV 3, PA-1), bladder (SCaBER), epidermis (A 431), lung (SW 900),
      breast (MDA-MB-231) and cervix (SiHa). CONCLUSIONS: Repifermin had no in vitro or
      in vivo proliferative effects on KGFR(+) human epithelial-like tumors. This
      failure to stimulate tumor cell growth highlights the ability of repifermin to
      specifically target normal epithelial tissue. This is critical to the safety
      profile of repifermin, since it is currently in phase II clinical trials for the
      treatment of cancer patients with mucositis resulting from chemo- or
      radiotherapy.

PMID- 12203103
TI  - Stimulation of TNF-alpha production by 2-(1-adamantylamino)-6-methylpyridine
      (AdAMP) - a novel immunomodulator with potential application in tumour
      immunotherapy.
AB  - The immunomodulatory effects of a recently synthesized adamantane derivative of
      aminopyridine - 2-(1-adamantylamino)-6-methylpyridine (AdAMP) - were tested on
      normal and neoplastic cells in vitro. When incubated with TNF-alpha gene
      transduced mouse melanoma cells (B78/TNF), AdAMP significantly enhanced basal
      production of TNF-alpha by these cells, both by "high" and "moderate" TNF-alpha
      producer cells. A similar TNF-alpha production-enhancing effect was observed in
      cultures of human ovarian carcinoma cells (CAOV1) which spontaneously produce TNF
      alpha but not in cultures of tumour cells incapable of TNF-alpha secretion. RT
      PCR analysis showed that the enhancement of TNF-alpha production by AdAMP was
      associated with an increase in TNF-alpha mRNA expression in the treated cells.
      The results of an electrophoretic mobility shift assay (EMSA) showed that AdAMP
      significantly activated nuclear factor kappaB (NF-kappaB) in both CAOV1 and
      B78/TNF cells. The role of NF-kappaB in enhancement of TNF-alpha production was
      confirmed in experiments in which MG132, an inhibitor of NF-kappaB activation,
      reversed the effect of AdAMP. Unexpectedly, dexamethasone, a potent
      antiinflammatory agent and a strong inhibitor of TNF-alpha production in vivo,
      increased both spontaneous and AdAMP-augmented production of TNF-alpha in in
      vitro cultures of ovarian carcinoma cells and B78/TNF cells. AdAMP also enhanced
      TNF-alpha secretion by LPS-induced monocytes. AdAMP-induced augmentation of TNF
      alpha production by B78/TNF cells was accompanied by morphological changes in the
      treated cells and a decrease in their adherence to fibrinogen and collagen IV. In
      view of these properties, AdAMP seems to be a therapeutically promising compound
      with potential application as an adjuvant augmenting the efficacy of cancer
      vaccine-based therapies or in the local treatment of certain tumours.

PMID- 12203104
TI  - Phase I and pharmacokinetic study of 3-aminopyridine-2-carboxaldehyde
      thiosemicarbazone (3-AP) using a single intravenous dose schedule.
AB  - PURPOSE: To perform a phase I and pharmacokinetics study of 3-aminopyridine-2
      carboxaldehyde thiosemicarbazone (3-AP) a new ribonucleotide reductase inhibitor
      using a single intravenous (2-h) schedule every 4 weeks. 3-AP was given at a
      starting dose of 5 mg/m(2) with escalation based on a modified Fibonacci scheme.
      PATIENTS AND METHODS: A total of 27 patients with advanced cancer were entered
      into the study. Doses of 3-AP ranged from 5 mg/m(2) to 105 mg/m(2). Blood and
      urine samples were collected and 3-AP was measured by HPLC. RESULTS: A total of
      46 courses were evaluable. One patient developed grade 4 thrombocytopenia at the
      lowest dose level, and one patient had grade 3 anemia. Two patients developed
      grade 3 coagulation abnormalities. The only other toxicities of more than grade l
      occurring in more than 10% of patients were fever and asthenia. No toxicities
      were observed at the highest dose level. Peak serum concentration of 3-AP
      increased linearly with dose. No tumor responses were observed in this heavily
      pretreated population, although eight patients had stabilization of their
      disease. CONCLUSIONS: Relevant tumor inhibitory concentrations were achieved
      without significant toxicity using doses up to 105 mg/m(2) on this single
      intravenous dose schedule. Prolonged administration schedules and combinations
      with other cytotoxic agents, strategies predicted to have greater antitumor
      efficacy according to preclinical studies, are under investigation.

PMID- 12203105
TI  - A formula for predicting optimal dosage of nedaplatin based on renal function in
      adult cancer patients.
AB  - PURPOSE: To predict the optimal dosage for nedaplatin ( cis
      diammineglycolatoplatinum), an anticancer drug and a platinum derivative like
      cisplatin and carboplatin, a simple formula was developed based on renal function
      in Japanese adult cancer patients. PATIENTS AND METHODS: Unbound platinum
      concentrations in plasma after intravenous infusion of nedaplatin were measured
      for 187 courses in 145 patients with lung, esophageal, and cervical and ovarian
      cancer undergoing clinical treatment. The data were divided into two sets, a
      model development data set of 94 courses and a validation data set of 93 courses.
      Regression analysis was applied to the relationship between the unbound platinum
      clearance (CL) of nedaplatin and the patients' renal function. The predictability
      and usefulness of this formula were assessed by validation using the external
      data set of 93 courses obtained from 75 patients. RESULTS: A simple formula was
      obtained for predicting the platinum clearance using the creatinine clearance
      (CLcr): CL=0.0836xCLcr+3.45. Indices for the predictive performance for CL and
      the area under the plasma concentration curve (AUC) in the validation data were
      almost the same as those for the model development data. CONCLUSIONS: A formula
      for predicting the CL of unbound platinum after nedaplatin administration was
      developed, and only CLcr was found to be a significant covariate of the CL. This
      formula was useful for estimating the CL for the second as well as the first
      treatment with nedaplatin.

PMID- 12203106
TI  - Recombinant human soluble tumor necrosis factor (TNF) receptor (p75) fusion
      protein Enbrel in patients with refractory hematologic malignancies.
AB  - PURPOSE: Tumor necrosis factor-alpha (TNF-alpha) is an important effector and
      regulatory cytokine involved in the pathophysiology of hematologic malignancies,
      including hairy cell leukemia (HCL), chronic lymphocytic leukemia (CLL),
      agnogenic myeloid metaplasia (AMM) and Philadelphia-negative myeloproliferative
      disorders (MPD). We conducted a pilot study to assess the safety of the soluble
      TNF receptor, etanercept (p75 TNFR:Fc; Enbrel) in patients with refractory
      hematologic malignancies. METHODS: Patients were eligible if they had refractory
      HCL, CLL, AMM, or Philadelphia-negative MPD. Enbrel was administered twice weekly
      at a dose of 25 mg subcutaneously for a minimum of eight doses, and was continued
      in patients without overt progression. RESULTS: Among the 26 patients enrolled on
      study, 25 patients were evaluable. Nine patients had AMM, eight CLL, three HCL,
      and five Philadelphia-negative MPD. Their median age was 60 years (range 30-83
      years). A total of 70 courses consisting of 486 doses of Enbrel were
      administered. Enbrel was well tolerated, without any overt increase in infectious
      episodes. Stable disease/no objective response was seen in 22 patients (88%) and
      progression in 3 patients (12%). Three patients with AMM improved (two showed
      hematologic improvement, and one showed a reduction in liver and spleen size),
      and two patients (one with CLL and one with Philadelphia-negative MPD) showed
      improvement in disease-related symptoms. CONCLUSIONS: Enbrel was well tolerated,
      but no responses were noted in these immunosuppressed patients with refractory
      hematologic malignancies.

PMID- 12203107
TI  - Population pharmacokinetic and limited sampling models for carboplatin
      administered in high-dose combination regimens with peripheral blood stem cell
      support.
AB  - OBJECTIVE: By means of a nonlinear mixed effect modeling technique, a population
      pharmacokinetic (PK) model was developed to evaluate the effects of a variety of
      covariates on clearance and other pharmacokinetic parameters of ultrafilterable
      carboplatin administered in high-dose combination regimens with peripheral blood
      stem cell support. In addition, single-sample and two-sample limited sampling
      models (LSMs) were derived to estimate carboplatin's AUC that could be used in
      the design of drug dosing regimens. METHODS: A total of 44 female patients with
      advanced ovarian cancer participated in two phase I studies. All 44 patients
      received a high-dose carboplatin chemotherapy with other anticancer drugs. A
      population PK model was applied to the plasma concentration-time data of
      ultrafilterable carboplatin using the NONMEM and Xpose computer programs. The
      Xpose program utilized a general additive modeling technique to identify
      significant patient covariates and PK parameter relationships. The resultant PK
      model was validated using a bootstrap method. Stepwise linear regression analyses
      were used to develop LSMs based on the correlation between carboplatin's AUC and
      plasma concentrations. RESULTS: The best structural covariate-free model for high
      dose carboplatin was a linear two-compartment model with an exponential error
      model to account for intersubject variability and a CCV error model to account
      for intrasubject variability. Subsequently, a final covariate model for clearance
      (l/min) was obtained as follows: TVCL=0.101+0011*(WT-62.35)-0.0658*(SCR-0.65)
      where WT is body weight (kg) and SCR is serum creatinine (mg/dl). Both WT and SCR
      were found to significantly influence carboplatin's total clearance. It was
      determined that the best single-sample LSM was AUC(LSM)=0.553*C(240min) (
      r=0.998). CONCLUSION: Both a population PK model and a LSM for high-dose
      carboplatin were developed following its administration in combination
      chemotherapeutic regimens with peripheral blood stem cell support. In both cases,
      the models performed well when analyzed in the context of the retrospective and
      bootstrap analyses. Prospective studies in ovarian cancer patients should be
      conducted to further tailor the current models.

PMID- 12203108
TI  - Extremely high exposures in an obese patient receiving high-dose
      cyclophosphamide, thiotepa and carboplatin.
AB  - An obese 53-year-old woman (height 167 cm, weight 130 kg) with metastatic breast
      cancer received high-dose chemotherapy comprising cyclophosphamide, thiotepa and
      carboplatin (CTC). The cyclophosphamide (1 g/m(2) per day) and thiotepa (80
      mg/m(2) per day) doses were based on body surface area (BSA) calculated using
      total body weight (TBW). The daily carboplatin dose was calculated based on the
      Calvert formula, using a target area under the plasma concentration-time curve
      (AUC) value of 3.25 mg.min/ml and applying the Cockcroft-Gault equation to
      estimate the glomerular filtration rate. The patient received the three agents as
      short infusions over four consecutive days. For therapeutic drug monitoring
      (TDM), blood samples were collected on day 1. Thiotepa and its main metabolite
      tepa, ultrafilterable platinum, cyclophosphamide and its activated metabolite 4
      hydroxycyclophosphamide were determined. Individual pharmacokinetics were
      assessed using Bayesian analysis. Exposure to the individual compounds was
      determined by calculating the AUC. Exposures to 4-hydroxycyclophosphamide, the
      combination of thiotepa/tepa and carboplatin were 94%, 117% and 71% higher than
      the median respective exposures in a non-obese population of patients ( n=24)
      receiving similar doses. Because high AUCs of 4-hydroxycyclophosphamide,
      thiotepa/tepa and carboplatin correlate with increased toxicity, the treatment
      risk in this obese patient was significantly increased. Therefore doses were
      adapted on the 3rd day of the course. It is concluded that cyclophosphamide and
      thiotepa in obese patients should not be dosed on the basis of BSA incorporating
      TBW since the patient will be overexposed. Moreover, applying the Cockcroft-Gault
      equation to obese patients leads to an overprediction of creatinine clearance
      and, when used in the Calvert equation, consequently to a carboplatin dose that
      is too high. Obese patients represent a unique group of patients in which TDM is
      extremely valuable in optimizing dosing, particularly in high-dose chemotherapy.

PMID- 12203109
TI  - Rhinoplasty: planning photo documentation and imaging.

PMID- 12203110
TI  - An activating mutation in the transmembrane domain of the granulocyte colony
      stimulating factor receptor in patients with acute myeloid leukemia.
AB  - To date, constitutively activating point mutations reported in hematopoietic
      growth factor receptors in patients with acute myeloid leukemia (AML) have been
      restricted to receptors with intrinsic tyrosine kinase activity such as c-kit and
      FLT3. We describe here a Thr617Asn mutation in the transmembrane domain of the
      non-tyrosine kinase receptor for granulocyte colony-stimulating factor (G-CSF) in
      the blast cells of two out of 555 AML patients examined. The mutant receptor
      conferred growth factor independence on factor-dependent Ba/F3 cells. In the
      absence of ligand, immunoblotting showed weak phosphorylation of JAK2, STAT3,
      ERKs 1 and 2 and the receptor itself, and there was approximately 70% of maximal
      growth in a proliferation assay. All signals were significantly enhanced in the
      presence of G-CSF. Retroviral transduction of mutant receptor into primary
      hematopoietic CD34+ cells induced G-CSF independent myeloid differentiation as
      assessed by the development of neutrophils and surface expression of CD11b and
      CD14. These results confirm the importance of the transmembrane domain for
      receptor function and suggest that introduction of an asparagine residue can
      cause sufficient stabilization of helix-helix interactions in the absence of
      ligand to activate downstream signaling pathways involved in directing
      proliferation and differentiation.

PMID- 12203111
TI  - Cellular transformation by a FERM domain mutant of the Nf2 tumor suppressor gene.
AB  - Mutations in the Nf2 tumor suppressor gene lead to tumor formation in humans and
      mice and cellular overproliferation phenotypes in Drosophila. The Nf2 encoded
      protein, merlin, shares close sequence similarity in its amino terminus to
      members of the band 4.1 family of membrane-cytoskeletal linkers. Similarities
      between merlin and this family suggest a role for merlin in regulating
      cytoskeletal function. However, the mechanism of the tumor suppressing activity
      of merlin is not yet understood. Mutational analysis of Nf2 in flies has led to
      the identification of a dominant-negative allele, which harbors mutations in the
      amino terminus of the protein. Here, we report that expression of a murine analog
      of this amino-terminal mutant of Nf2 leads to complete transformation of NIH3T3
      fibroblasts in culture. Cells that express this Nf2 mutant allele display
      disruptions of the actin cytoskeleton, lack of contact inhibition of growth, and
      anchorage-independent growth. Finally, fibroblasts that express this mutant Nf2
      allele form tumors when injected into nude mice.

PMID- 12203112
TI  - RhoB controls the 24 kDa FGF-2-induced radioresistance in HeLa cells by
      preventing post-mitotic cell death.
AB  - Farnesylated Ras oncoprotein induces a cellular resistance to ionizing radiation
      that can be reversed by farnesyltransferase inhibitors (FTI). We previously
      demonstrated that, expression of the 24 kDa FGF2 isoform in wild type ras bearing
      HeLa cells, induced radioresistance which was also reversed by FTI. We tested the
      hypothesis that wild type Ras or RhoB, which has been proposed as a potential FTI
      target, could control the FGF-2-induced radioresistance mechanisms. For this, we
      expressed inducible dominant negative forms of Ras (RasN17) and Rho (RhoBN19) in
      24 kDa FGF2 transfected HeLa cells and analysed their survival after irradiation.
      While no cell survival modification was observed after RasN17 induction, the
      expression of RhoBN19 induced a radiosensitization of FGF2 radioresistant HeLa
      cells in the same range as the one observed after a 48 h treatment with the
      specific FTI, R115777. Moreover, we showed that activated RhoB but not RhoA
      induced radioresistance in NIH3T3 cells. The radiosensitizer effect of RhoBN19
      expression was due to the induction of the radiation induced post-mitotic cell
      death. Taken together, these data demonstrate that 24 kDa FGF-2-induced
      radioresistance is controlled by Rho pathways and suggest that RhoB should be a
      major determinant in cellular resistance to ionizing radiation.

PMID- 12203113
TI  - Alternative first exons of PTCH1 are differentially regulated in vivo and may
      confer different functions to the PTCH1 protein.
AB  - The PTCH1 gene is a human tumour suppressor gene frequently mutated in basal cell
      carcinoma (BCC) and several other tumour types. It encodes a receptor for soluble
      factors of the hedgehog family. Binding of hedgehog to the receptor relieves its
      inhibitory action on the transmembrane co-receptor Smoh. In this study we
      describe alternative first exons of the PTCH1 tumour suppressor gene and show
      that they are differentially regulated in normal tissues, exon 1B being expressed
      at very low levels and the major mRNA species containing exon 1 or 1A. Exon 1B
      transcripts were found to be specifically upregulated in nodular BCCs. The
      different PTCH1 transcripts all encode proteins that interact with Smoh in doubly
      transfected cells. Furthermore, functional assays demonstrated that whereas all
      PTCH1 isoforms can inhibit the activity of SHH, only the PTCH1B isoform is
      capable of fully inhibiting Smoh activity. The results indicate that in tumour
      cells the PTCH1B promoter is specifically activated and importantly, that the N
      terminal part of PTCH1 including exon 1B is required for full inhibition of Smoh
      signaling but not for physical interaction with Smoh.

PMID- 12203114
TI  - Identification of a novel stress-responsive gene Hi95 involved in regulation of
      cell viability.
AB  - cDNA microarray hybridization was used in an attempt to identify novel genes
      participating in cellular responses to prolonged hypoxia. One of the identified
      novel genes, designated Hi95 shared significant homology to a p53-regulated GADD
      family member PA26. In addition to its induction in response to prolonged
      hypoxia, the increased Hi95 transcription was observed following DNA damage or
      oxidative stress, but not following hyperthermia or serum starvation. Whereas
      induction of Hi95 by prolonged hypoxia or by oxidative stress is most likely p53
      independent, its induction in response to DNA damaging treatments (gamma- or UV
      irradiation, or doxorubicin) occurs in a p53-dependent manner. Overexpression of
      Hi95 full-length cDNA was found toxic for many types of cultured cells directly
      leading either to their apoptotic death or to sensitization to serum starvation
      and DNA damaging treatments. Unexpectedly, conditional overexpression of the Hi95
      cDNA in MCF7-tet-off cells resulted in their protection against cell death
      induced by hypoxia/glucose deprivation or H(2)O(2). Thus, Hi95 gene seems to be
      involved in complex regulation of cell viability in response to different stress
      conditions.

PMID- 12203115
TI  - Apo2L/TRAIL differentially modulates the apoptotic effects of sulindac and a COX
      2 selective non-steroidal anti-inflammatory agent in Bax-deficient cells.
AB  - The nonsteroidal anti-inflammatory drugs (NSAIDs) are believed to mediate their
      anticancer effects by inducing apoptosis but the molecular mechanisms of their
      apoptotic effects remain largely unknown. Here we report that two different
      NSAIDs, sulindac sulfide and SC-'236 engage the death receptor 5 (DR5) and
      mitochondrial pathways to mediate apoptosis in human colon cancer cells. We show
      that sulindac sulfide and SC-'236-induced apoptosis is coupled with upregulation
      of DR5, caspase 8 activation and Bid cleavage. Thus, a cross talk appears to
      exist between the DR5 and mitochondrial pathways during apoptosis induced by
      these NSAIDs. We further show that sulindac sulfide and SC-'236-induced DR5
      upregulation occurs independent of the COX inhibitory effects of these NSAIDs.
      Using Bax-proficient (Bax+/-) and Bax-deficient (Bax-/-) HCT116 human colon
      cancer cells, we further demonstrate that Apo2L/TRAIL differentially modulates
      the apoptotic effects of sulindac sulfide and SC-'236. For example, sulindac
      sulfide upregulates DR5 in both Bax-deficient and proficient cells, but
      Apo2L/TRAIL efficiently potentiates sulindac sulfide-induced apoptosis as well as
      activation of caspase-8, -9 and -3 only in Bax-proficient cells. SC-'236 also
      upregulates DR5 in both Bax-proficient and Bax-deficient cells but Apo2L/TRAIL
      potentiates SC-'236-mediated apoptosis and caspases-8 and -3 activation in both
      Bax-proficient and Bax-deficient cells. Further, in Bax-deficient cells, neither
      sulindac sulfide nor SC-'236 in combination with Apo2L/TRAIL effectively promotes
      the release of cytochrome c from mitochondria into cytosol and caspase-9
      activation. Collectively, our results suggest that unlike sulindac sulfide, SC
      '236 in combination with Apo2L/TRAIL can overcome Bax deficiency to induce
      apoptosis. These results have important clinical implications in that the tumors
      harboring Bax mutations are likely to develop resistance to sulindac but not to
      SC-'236-like NSAIDs. In conclusion, the data presented herein form the basis of
      future in-depth studies to further explore the utility of Apo2L/TRAIL and NSAIDs,
      in combination, as a novel cancer preventive/therapeutic strategy.

PMID- 12203116
TI  - Selective silencing of viral gene expression in HPV-positive human cervical
      carcinoma cells treated with siRNA, a primer of RNA interference.
AB  - Selective silencing of mammalian gene expression has recently been achieved using
      short interfering RNA (siRNA). Synthetic siRNA targets homologous mRNA for
      degradation and the process is highly efficient. Here we demonstrate siRNA
      silencing of pathogenic viral gene expression. As a well characterized model we
      chose cervical carcinoma cells positive for human papillomavirus type 16. Over
      90% of human cervical cancers are positive for papillomavirus and abnormal cell
      proliferation is driven by co-operative effects of viral E6 and E7 genes. We
      sought to silence HPV E6 and E7 gene expression using siRNAs to target the
      respective viral mRNAs. Our results indicate selective degradation of E6 and E7
      mRNAs. Silencing was sustained for at least 4 days following a single dose of
      siRNA. E6 silencing induced accumulation of cellular p53 protein, transactivation
      of the cell cycle control p21 gene and reduced cell growth. In contrast, E7
      silencing induced apoptotic cell death. HPV-negative cells appeared unaffected by
      the anti-viral siRNAs. Thus we demonstrate for the first time (i) that siRNA can
      induce selective silencing of exogenous viral genes in mammalian cells, and (ii)
      that the process of siRNA interference does not interfere with the recovery of
      cellular regulatory systems previously inhibited by viral gene expression.

PMID- 12203117
TI  - Smad4 induces the tumor suppressor E-cadherin and P-cadherin in colon carcinoma
      cells.
AB  - Smad4 is an intracellular transmitter of TGF-beta signals and its tumor
      suppressor function is presumed to reside in its capacity to mediate TGF-beta
      induced growth inhibition. However, there is accumulating evidence that this
      hypothesis may be too simple. The roles of TGF-beta in carcinogenesis are complex
      and also comprise tumor promoting functions particularly in late stage
      carcinogenesis. Importantly, functional inactivation of Smad4 in colon carcinomas
      frequently occurs at late stages when tumors acquire invasive and metastatic
      capabilities. We have previously reported that stable re-expression of Smad4 in
      SW480 human colon carcinoma cells was adequate to suppress tumor growth in nude
      mice. However, it did not affect cell growth in vitro nor did it restore TGF-beta
      responsiveness. Here, we report that Smad4 transcriptionally induced classical
      cadherins including the invasion suppressor E-cadherin, presumably re
      establishing epithelial morphology. Smad4-induced cadherins were able to recruit
      catenins to the plasma membrane and were functionally active in cell-cell
      adhesion. These results indicate a novel pathway of Smad4-mediated tumor
      suppression and suggest that Smad4 in colon cells may be involved in the
      maintenance of epithelial traits.

PMID- 12203118
TI  - Increased arylhydrocarbon receptor expression offers a potential therapeutic
      target for pancreatic cancer.
AB  - The arylhydrocarbon receptor (AhR) was initially identified as a member of the
      adaptive metabolic and toxic response pathway to polycyclic aromatic hydrocarbons
      and to halogenated dibenzo-p-dioxins and dibenzofurans. In the present study, we
      sought to determine the functional significance of the AhR pathway in pancreatic
      carcinogenesis. AhR expression was analysed by Northern blotting. The exact site
      of AhR expression was analysed by in situ hybridization and immunohistochemistry.
      The effects of TCDD and four selective AhR agonists on pancreatic cancer cell
      lines were investigated by growth assays, apoptosis assays, and induction of the
      cyclin-dependent kinase inhibitor p21. There was strong AhR mRNA expression in 14
      out of 15 pancreatic cancer samples, weak expression in chronic pancreatitis
      tissues, and faint expression in all normal pancreata. In pancreatic cancer
      tissues, AhR mRNA and protein expression were localized in the cytoplasm of
      pancreatic cancer cells. TCDD and the four AhR agonists inhibited pancreatic
      cancer cell growth in a dose-dependent manner, and decreased anchorage
      independent cell growth. DAPI staining did not reveal nuclear fragmentation and
      CYP1A1 and was not induced by TCDD and AhR agonists. In contrast, TCDD and AhR
      agonists induced the expression of the cyclin-dependent kinase inhibitor p21. In
      conclusion, the relatively non-toxic AhR agonists caused growth inhibition in
      pancreatic cancer cells with high AhR expression levels via cell cycle arrest. In
      addition, almost all human pancreatic cancer tissues expressed this receptor at
      high levels, suggesting that these or related compounds may play a role in the
      therapy of pancreatic cancer in the future.

PMID- 12203119
TI  - Tumour necrosis factor-alpha in Barrett's oesophagus: a potential novel mechanism
      of action.
AB  - Barrett's metaplasia (BM) is an early lesion in the progression from oesophageal
      inflammation through dysplasia to the development of Barrett's adenocarcinoma
      (BA). Previous work indicates that BM and BA are associated with reduced E
      cadherin expression and increased cytoplasmic/nuclear pools of its associated
      protein beta-catenin. beta-catenin participates in Wnt signalling and activates
      oncogene transcription by complexing with T-cells factors (TCF). One such
      oncogene is c-myc. We have previously shown that TNF-alpha can down-regulate E
      cadherin expression. Here, we assess TNF-alpha expression in Barrett's metaplasia
      and examine if TNF-alpha can promote beta-catenin mediated transcription of
      oncogenes in a gastrointestinal model system. Employing immunohistochemistry and
      Western blot analysis of oesophageal tissue, epithelial expression of TNF-alpha
      increases with progression along the metaplasia-dysplasia-carcinoma sequence
      (P<0.001). beta-catenin mediated transcription was then assessed in TNF-alpha
      stimulated cell lines using the TOPFLASH reporter system whilst c-myc expression
      was assessed by real time PCR. In a columnar intestinal cell model, TNF-alpha
      induces c-myc expression which is induced via beta-catenin mediated transcription
      (P<0.05). This beta-catenin mediated transcription is independent of NF-kappaB
      activation. Thus, TNF-alpha is up-regulated in the progression of Barrett's
      oesophagus and beta-catenin mediated transcription of c-myc is a novel pathway
      whereby elevated levels of TNF-alpha may lead to oncogene transcription and
      altered biology in gastrointestinal epithelia and metaplasia.

PMID- 12203120
TI  - Critical roles of AMP-activated protein kinase in constitutive tolerance of
      cancer cells to nutrient deprivation and tumor formation.
AB  - As tumors grow and invade beyond their homeostatic limits, the tumor cells are
      subjected to insufficient nutrient and oxygen supplies because of excessive
      demand for nutrition and oxygen, and insufficient vascularization. We therefore
      hypothesized that tolerance to nutrient deprivation as well as angiogenesis may
      be critical in some malignancies, including pancreatic cancers, which are seen to
      be a hypovascular tumor. In this study, we assessed the effect of AMP-activated
      protein kinase (AMPK), which plays a major role in protecting cells from
      metabolic stresses, on tumor biology under nutrient-deprived condition. Whereas
      hepatic cancer cells had mostly died within 48 h during glucose deprivation, most
      pancreatic cancer cells survived more than 48 h. The tolerance to glucose
      deprivation tended to correlate with the cells level of expression of AMPK alpha1
      and alpha2. The introduction of AMPK antisense RNA expression vectors into
      pancreas cancer cell lines, PANC-1 and AsPC-1, significantly diminished their
      tolerance to glucose deprivation, and the stable transfection of AMPK antisense
      into PANC-1 cells inhibited tumor growth in nude mice. These findings indicate
      that AMPK expression contributes to tolerance to nutrient starvation in cancer
      cells. We propose AMPK as a new target for therapeutic strategies to suppress
      tumor growth and invasion.

PMID- 12203121
TI  - An atypical caspase-independent death pathway for an immunogenic cancer cell
      line.
AB  - REGb cell line, a highly immunogenic tumor cell variant isolated from a rat colon
      cancer, yields regressive tumors when injected into syngeneic hosts. We
      previously demonstrated that REGb tumor immunogenicity was related to the
      capacity of releasing dead cells in vivo. Also, in vitro, REGb cell monolayers
      release dead cells, especially when cultured in serum-free medium. In the current
      study, we show that the release of dead cells results from an atypical death
      process associating features of necrosis and apoptosis. In spite of features
      considered as hallmarks of caspase-dependent apoptosis, including chromatin
      fragmentation and DNA oligonucleosomal cleavage, caspases are not activated and
      caspase inhibitors are ineffective to prevent REGb cell death. In contrast with a
      number of other types of cell death, the spontaneous death of REGb cells in
      culture depends on de novo protein synthesis as this death is blocked by low
      doses of the mRNA translation inhibitor cycloheximide. This unusual mode of cell
      death that associates necrotic and apoptotic features could provide optimal
      conditions for triggering a specific immune response.

PMID- 12203122
TI  - cAMP inhibits the proliferation of retinal pigmented epithelial cells through the
      inhibition of ERK1/2 in a PKA-independent manner.
AB  - Retinal pigmented epithelial (RPE) cell integrity is critical to the maintenance
      of retina functions and RPE cells do not proliferate in adults. The activation of
      RPE results in cell proliferation which may be associated with proliferative
      retinopathy and choroidal melanoma. Mitogen-activated protein kinase (MAPK) is
      believed to be a key participant in the response to mitogenic stimuli. We
      therefore investigated the involvement of the extracellular signal-regulated
      protein kinase (ERK) 1 and 2 during the induction of RPE cell proliferation.
      After foetal calf serum (FCS) stimulation activation of the Ras/Raf/ERK
      signalling pathway was detected by Western blotting and immunochemistry, with
      specific anti-phosphosignalling protein antibodies. Pharmacological and antisense
      (AS) oligonucleotide (ODN) strategies were used to analyse the signalling
      involved in FCS-induced RPE cell proliferation. Activation of the small G protein
      Ras and, to a lesser extent of Raf-1, the kinase directly downstream from Ras,
      was necessary to FCS-induced cell proliferation. MEK1/2 and ERK1/2 were activated
      during cell proliferation. Inhibition of MEK1/2 with UO 126 completely abolished
      ERK1/2 activation and reduced cell proliferation by 33-43%. ERK1/2 depletion by
      an AS ODN approach reduced cell proliferation by 27-33%, confirming the role of
      ERK1/2 in the FCS stimulation of RPE cells. We also investigated the role of
      PKA/cAMP, one of the major inhibitory pathways of ERK1/2. PKA blockade did not
      modify ERK1/2 activation or cell proliferation. In contrast, agents that
      increased cAMP concentration, abolished RPE proliferation, and MEK/ERK
      activation. Moreover, inhibition of the cAMP-activated small G protein Rap1,
      partially reversed the inhibitory effects of cAMP on cell proliferation and
      MEK/ERK activation. The requirement for Ras and ERK1/2, the lack of ERK1/2
      regulation by PKA and the cAMP/Rap1 counter-regulatory pathway for ERK-mediated
      cell proliferation suggest complex regulation of signalling in RPE cells. These
      data may have important implications for the development of more selective models
      for retinal anti-proliferative therapies.

PMID- 12203123
TI  - Novel target for induction of apoptosis by cyclo-oxygenase-2 inhibitor SC-236
      through a protein kinase C-beta(1)-dependent pathway.
AB  - Nonsteroidal anti-inflammatory drugs (NSAIDs) reduce the risk of gastrointestinal
      cancers. Recently, a similar protective effect has been demonstrated by the
      specific cyclo-oxygenase-2 (COX-2) inhibitors. However, the exact mechanism that
      accounts for the anti-proliferative effect of specific COX-2 inhibitors is still
      not fully understood, and it is still controversial whether these protective
      effects are predominantly mediated through the inhibition of COX-2 activity and
      prostaglandin synthesis. Identification of molecular targets regulated by COX-2
      inhibitors could lead to a better understanding of their pro-apoptotic and anti
      neoplastic activities. In the present study, we investigated the effect and the
      possible molecular target of a COX-2-specific inhibitor SC-236 on gastric cancer.
      We showed that SC-236 induced apoptosis in gastric cancer cells. However, this
      effect was not dependent on COX-2 inhibition. SC-236 down-regulated the protein
      expression and kinase activity of PKC-beta(1), increased the expression of
      PKCdelta and PKCeta, but did not alter the expression of other PKC isoforms in
      AGS cells. Moreover, exogenous prostaglandins or PGE(2) receptor antagonists
      could not reverse the inhibition effect on PKCbeta(1) by SC-236, which suggested
      that this effect occurred through a mechanism independent of cyclo-oxygenase
      activity and prostaglandin synthesis. Overexpression of PKCbeta(1) attenuated the
      apoptotic response of AGS cells to SC-236 and was associated with overexpression
      of p21(waf1/cip1). Inhibition of PKCbeta(1)-mediated overexpression of
      p21(waf1/cip1) partially reduced the anti-apoptotic effect of PKCbeta(1). The
      down-regulation of PKCbeta(1) provides an explanation for COX-independent
      apoptotic effects of specific COX-2 inhibitor in cultured gastric cancer cells.
      We also suggest that PKCbeta(1) act as survival mediator in gastric cancer, and
      its down-regulation by COX-2 inhibitor SC-236 may provide new target for future
      treatment of gastric cancer.

PMID- 12203124
TI  - The Brn-3a transcription factor inhibits the pro-apoptotic effect of p53 and
      enhances cell cycle arrest by differentially regulating the activity of the p53
      target genes encoding Bax and p21(CIP1/Waf1).
AB  - We have previously shown that the anti-apoptotic transcription factor, Brn-3a and
      the pro-apoptotic p53 factor have antagonistic effects on the promoter of the
      gene encoding the anti-apoptotic Bcl-2 protein, with p53 abolishing activation by
      Brn-3a. Here we demonstrate that this antagonism is also observed on the gene
      encoding the pro-apoptotic Bax protein with Brn-3a abolishing the ability of p53
      to activate the Bax promoter and induce Bax protein expression. In contrast, Brn
      3a and p53 co-operative to induce maximal activation of another p53 target gene
      encoding the cyclin dependent kinase inhibitor, p21(CIP1/Waf1). These
      differential effects of Brn-3a on p53-inducible genes involved in apoptosis or
      growth arrest are paralleled by its effects on these processes themselves. Thus,
      we show that Brn-3a antagonises the anti-apoptotic effect of p53 but co-operates
      with p53 to induce cell cycle arrest. The potential role of Brn-3a in determining
      the outcome of enhanced p53 levels is discussed.

PMID- 12203125
TI  - Doxorubicin-induced death in neuroblastoma does not involve death receptors in S
      type cells and is caspase-independent in N-type cells.
AB  - Death induced by doxorubicin (dox) in neuroblastoma (NB) cells was originally
      thought to occur via the Fas pathway, however since studies suggest that caspase
      8 expression is silenced in most high stage NB tumors, it is more probable that
      dox-induced death occurs via a different mechanism. Caspase-8 silenced N-type
      invasive NB cell lines LAN-1 and IMR-32 were investigated for their sensitivity
      to dox, and compared to S-type noninvasive SH-EP NB cells expressing caspase-8.
      All cell lines had similar sensitivities to dox, independently of caspase-8
      expression. Dox induced caspase-3, -7, -8 and -9 and Bid cleavage in S-type cells
      and death was blocked by caspase inhibitors but not by oxygen radical scavenger
      BHA. In contrast, dox-induced death in N-type cells was caspase-independent and
      was inhibited by BHA. Dox induced a drop in mitochondrial membrane permeability
      in all cell lines. Dox-induced death in S-type cells gave rise to apoptotic
      nuclei, whereas in N-type cells nuclei were non-apoptotic in morphology.
      Transfection of SH-EP cells with a dominant negative FADD mutant inhibited TRAIL
      induced death, but had no effect on dox-induced apoptosis. These results suggest
      that S-type cells undergo apoptosis after dox treatment independently of death
      receptors, whereas N-type cells are killed by a caspase-independent mechanism.

PMID- 12203126
TI  - Lingual and buccal mandibular bone depressions: a review based on 583 cases from
      a world-wide literature survey, including 69 new cases from Japan.
AB  - OBJECTIVES: To review present knowledge of so-called lingual and buccal
      mandibular bone depressions (n = 583) based on studies of 247 contemporary and
      267 archaeological cases from a world-wide literature survey in addition to 69
      new cases from Japan. METHODS: The 69 cases from Japan were retrieved through
      examination of 42,600 consecutive panoramic radiographs. RESULTS: Bone
      depressions can be divided into four topographical variants: (1) lingual anterior
      mandibular body (incisor-canine- premolar area) above the mylohyoid muscle; (2)
      posterior to the mandibular angle-first permanent molar area, below the
      mandibular canal, and a third located to the ascending, lingual mandibular ramus,
      posterior to the lingual foramen, just below the neck of the condyle. An
      excessively rare fourth variant is located to the buccal aspects of the ascending
      mandibular ramus. CONCLUSIONS: The present concept favours that all variants have
      a common origin: a hyperplastic/hypertrophic lobe (or aberrant lobe) of the
      sublingual, submandibular or parotid salivary gland, exerting pressure upon the
      cortex of the mandible by the respective gland, leading to focal atrophy or
      resorption of the bone. The bone depressions take years to develop, appearing
      radiographically not until the 5th to 6th decades.

PMID- 12203127
TI  - A sequential approach to radiological interpretation.
AB  - A case of large glandular odontogenic cyst of the mandible is presented in which
      the panoramic radiograph also demonstrated a soft tissue lesion consistent with
      carotid aneurysm. CT confirmed the bucco-lingual extent of the mandibular lesion
      and the presence of a soft tissue lesion consistent with an aneurysm of the
      internal carotid artery. CT angiography, MR angiography and US were used to rule
      out a carotid artery aneurysm prior to surgery of the mandibular lesion.

PMID- 12203128
TI  - Accuracy of tuned aperture computed tomography in the diagnosis of radicular
      fractures in non-restored maxillary anterior teeth--an in vitro study.
AB  - OBJECTIVES: This study compared the accuracy of three radiographic imaging
      modalities for the detection of artificially induced radicular fractures on
      maxillary anterior teeth. METHODS: Fractures were induced in 28 of 54 maxillary
      incisors in 15 cadaver specimens using a distally directed force. Radiographs
      evaluated included conventional two-dimensional direct digital radiographs (DDI),
      unprocessed Tuned Aperture Computed Tomography (TACT-U) and iteratively restored
      TACT (TACT-IR). Eight observers recorded their findings using a five-point
      confidence-rating scale. Receiver Operating Characteristic (ROC) analyses were
      done, followed by ANOVA to test for significant effects of observers, imaging
      modality and fracture location. Post hoc tests were carried out in instances
      where ANOVA indicated significance. RESULTS: The areas under the ROC-curves
      (A(z)) were, respectively: DDI: 0.53; TACT-U: 0.83 and TACT-IR: 0.97. TACT-IR and
      TACT-U performed significantly better than DDI (P < 0.001) with TACT-IR providing
      a higher detection accuracy than TACT-U (P < 0.033). A difference in detection
      accuracy was also noted based on fracture location (P < 0.001). Tukey's post hoc
      analyses revealed that fractures extending beyond the middle third of the root
      were more accurately detected. Inter-observer agreement was 0.68, and intra
      examiner agreement, 0.87 (kappa analysis). CONCLUSIONS: TACT performed
      significantly better than direct digital images in detecting trauma-induced
      radicular fractures in unrestored, maxillary anterior teeth.

PMID- 12203129
TI  - Utility of frequency-selective fat saturation T2-weighted MR images for the
      detection of joint effusion in the temporomandibular joint.
AB  - OBJECTIVES: To evaluate joint effusion in the temporomandibular joint (TMJ) using
      frequency-selective fat saturation (FS) T2-weighted images and assess this
      technique. To investigate whether bone marrow abnormalities and magnetic
      resonance imaging (MRI) findings of internal derangement may be linked to joint
      effusion in the TMJ in patients with pain. METHODS: TMJ effusion was sought on FS
      T2-weighted images and conventional T2-weighted images in 400 joints from 200
      patients with TMJ-related pain. Self-reported pain records were obtained from
      patients immediately before MRI and images assessed by the amount of TMJ fluid
      graded bilaterally using reference films by two radiologists. Other parameters
      recorded included disk displacement categories and condyle marrow abnormalities.
      The association between the recorded parameters and TMJ effusion judged by FS
      sequences or conventional sequences was analysed using chi-square and Kappa
      tests. RESULTS: The detection rate of TMJ effusion by FS-sequences was
      significantly greater than by conventional methods, and the results showed a
      significant relationship between MRI interpretation of TMJ effusion using FS
      sequences or conventional methods and the presence of pain. The correlation
      between TMJ effusion on FS-sequences and pain was significantly stronger than the
      conventional method. Kappa test indicated good agreement between pain and MRI TMJ
      effusion by FS-sequences (kappa = 0.66), but not by conventional sequences (kappa
      = 0.56). The other parameters showed a similar trend for TMJ-related pain.
      CONCLUSIONS: FS T2-weighted imaging is useful for detection of TMJ effusion,
      without known causes and confirms the importance of TMJ effusion as an indicator
      in patients with TMJ-related pain, bone abnormalities, and disk displacement.

PMID- 12203130
TI  - A new device for measuring density of jaw bones.
AB  - OBJECTIVES: The purpose of this project was to develop a lightweight, simple
      device to evaluate alveolar process bone density using normal intraoral and
      extraoral imaging procedures. METHODS: A simple lightweight device was
      constructed using barium sulfate as the major radiopaque component. The 5 x 32 x
      12 mm(3) resin block has eight segments with known densities ranging from 1.304
      (g/cm(3)) to 1.982 (g/cm(3)). The device was integrated into an XCP unit for
      standard intraoral radiographs and placed between the jaws for computer aided
      tomographic imaging. The relationship between the device segment densities and
      the optical densities of the exposed film was plotted. RESULTS: A linear inverse
      relationship was found between the device segment densities and optical densities
      when segment densities were between 1.304 (g/cm(3)) to 1.882 (g/cm(3)). However,
      the relationship was non-linear for segment densities above 1.882 (g/cm(3)).
      CONCLUSIONS: Normal human bone density is 1.85 (g/cm(3)), and this densitometer
      is useful for determination of material densities from 1.304 (g/cm(3)) to 1.882
      (g/cm(3)). The device may be useful for precise bone density assessment.

PMID- 12203131
TI  - Radiographic practices of dentists undertaking endodontics in New Zealand.
AB  - OBJECTIVES: To determine the radiographic practices of New Zealand dentists
      undertaking root canal treatment, and to investigate the relationship between
      radiographic practices and educational and clinical factors. METHODS: A
      questionnaire was sent to all 1200 general dental practitioners and five
      specialist endodontists in New Zealand. Data were subjected to descriptive and
      analytical statistics. RESULTS: The response rate was 79%. The mean number of
      root canal treatments done by general dentists in the previous 12 months was 103,
      and for the specialists 938. Pre-operative views were taken by 57.1% of
      respondents all the time and by 34.8% in most cases. The long cone paralleling
      and bisecting angle techniques were in regular use by similar numbers of
      respondents, and over one half of the practitioners regularly used film holders
      and electronic apex locators. Working length films were taken by 67% of
      practitioners all the time and by 18% in most cases. One-quarter of practitioners
      took a master point view all the time, and 15% did this for most cases. Almost
      65% always took a film of the completed root filling and 21% did for most cases.
      Twenty-three per cent of practitioners did not follow up their work. CONCLUSIONS:
      The majority of respondents used radiographs pre-operatively, for working length
      assessment and to assess the final root filling. There was a general improvement
      in radiographic practices compared with data from a previous national survey held
      in 1980.

PMID- 12203133
TI  - Radiographic diagnosis of Limbus vertebra on a lateral cephalometric film: report
      of a case.
AB  - Although Limbus vertebra is not an uncommon radiological finding in an adult, it
      is a rare finding in the child or adolescent. The most common site for the
      presence of Limbus vertebra is the mid-lumbar region and less commonly occurs in
      the mid cervical region. It is a defect (tiny unfused apophyseal fragment) in the
      anterior margin of the vertebral body usually at the superior anterior margin in
      the lumbar vertebrae and at the anteroinferior margin in the cervical vertebrae.
      These margins are the sites of epiphyseal centers on vertebrae. A case of Limbus
      vertebra seen on a routine lateral cephalometric radiograph taken prior to
      Orthodontic treatment is reported and the literature is reviewed. The Limbus
      vertebra is thought to result from herniation of the nucleus pulposus through the
      ring apophysis prior to fusion isolating a small segment of the vertebral rim.
      This could be mistaken for a fracture, infection or tumor resulting in further
      invasive diagnostic procedures. It is important to recognize that this represents
      the sequela of a remote injury in an immature skeleton. A sound knowledge of this
      anomaly is essential for all clinicians so that appropriate measures can be taken
      without unduly alarming patients.

PMID- 12203132
TI  - Appearance, location, course, and morphology of the mandibular incisive canal: an
      assessment on spiral CT scan.
AB  - OBJECTIVES: To assess the appearance, location, and course of the incisive canal
      as compared to other anatomical landmarks on spiral CT of the mandible. METHODS:
      Study material included 230 spiral CT scans taken for preoperative planning of
      implant placement in the posterior mandible. All scanning was performed using a
      standard exposure and patient positioning protocol. Axial, panoramic, and
      reformatted cross-sectional images were carefully examined. Visibility of the
      incisive canal and other anatomical landmarks was scored using a four-point
      rating scale. The vertical and buccolingual diameter of the outer contour as well
      the diameter of the inner contour of the incisive canal were measured using a
      digital sliding caliper. RESULTS: An incisive canal was identified in 93% of the
      cases, with good visibility in 22% of the cases. Mean (s.d.) vertical diameter,
      buccolingual diameter, and inner diameter of the incisive canal were 4.7 (1.1),
      3.7 (0.7), and 1.1 (0.3) mm respectively. The mandibular canal, mental foramen,
      lingual foramen, and anterior looping appeared in 98, 100, 82 and 7% of the
      images respectively. CONCLUSIONS: A well-defined incisive canal could be detected
      in the majority of spiral CT scans. Its radiographic detection remained lower
      than for the mandibular canal or mental foramen, but higher than for the
      visibility of the lingual foramen. Visualisation of the incisive canal and the
      occasional presence of an anterior looping, demonstrates the potential value of
      cross-sectional imaging of the anterior mandible for presurgical planning
      purposes.

PMID- 12203135
TI  - Bone marrow transplantation for myelodysplastic syndrome--who? when? and which?
AB  - Although allogeneic transplantation has resulted in long-term disease-free
      survival in some patients with myelodysplastic syndromes (MDS), the morbidity and
      mortality of this approach remains high. Additionally, many patients are not
      candidates for such an approach because of their age or comorbid factors.
      Autologous transplantation and the use of reduced intensity conditioning prior to
      allogeneic stem cell transplantation has provided less toxic alternatives as well
      as increased the numbers of patients eligible for some form of transplantation.
      While bone marrow transplantation clearly has a role in the treatment of MDS, the
      decision to proceed to transplantation is not always easy and the optimal
      approach has not been clearly defined. Improvement in patient selection and novel
      approaches to transplantation will hopefully allow for more effective, less toxic
      results.

PMID- 12203136
TI  - Reduced intensity conditioning regimen followed by glycosylated G-CSF mobilized
      PBSCT in patients with solid tumors and malignant lymphomas.
AB  - The aim of this pilot study was to exploit the graft-versus-tumor potential of
      allogeneic transplants while improving safety of the procedure. Twelve patients
      with advanced hematological malignancies and solid tumors underwent a low
      intensity conditioning regimen (fludarabine and cyclophosphamide) followed by an
      allogeneic peripheral blood stem cell transplantation. The median time to achieve
      an absolute neutrophil count of more than 0.5 x 10(9)/l and an untransfused
      platelet count of more than 20 x 10(9)/l was 15 and 14 days, respectively. The
      main extra-hematological toxicities were mucositis and infections. Acute graft
      versus-host (GVHD) disease was experienced by 62% of evaluable patients (grade
      II/B or III/C 80%) responsive to steroids. Extensive chronic GVHD was observed in
      62% of patients. Non-relapse transplant-related mortality by day +30 was observed
      in three patients (25%). Eight out of 12 patients were full donor chimeric by day
      +100. One patient showed a mixed chimerism at day +37 when he died from
      progressive disease. One patient was in complete remission (CR) before allogeneic
      transplantation, and after transplantation four patients achieved CR and four
      experienced progressive disease. Our study confirms that a low intensity
      conditioning regimen for allogeneic stem cell transplantation is feasible and
      effective in heavily pretreated patients.

PMID- 12203137
TI  - Allogeneic mesenchymal stem cell infusion for treatment of metachromatic
      leukodystrophy (MLD) and Hurler syndrome (MPS-IH).
AB  - Patients with Hurler syndrome (mucopolysaccharidosis type-IH) and metachromatic
      leukodystrophy (MLD) develop significant skeletal and neurologic defects that
      limit their survival. Transplantation of allogeneic hematopoietic stem cells
      results in partial correction of the clinical manifestations. We postulated that
      some of these defects may be corrected by infusion of allogeneic, multipotential,
      bone marrow-derived mesenchymal stem cells (MSC). Patients with Hurler syndrome
      (n = 5) or MLD (n = 6) who previously underwent successful bone marrow
      transplantation from an HLA-identical sibling were infused with 2-10 x 10(6)/kg
      MSCs, isolated and expanded from a bone marrow aspirate of the original donor.
      There was no infusion-related toxicity. In most recipients culture-purified MSCs
      at 2 days, 30-60 days and 6-24 months after MSC infusion remained of host type.
      In two patients the bone marrow-derived MSCs contained 0.4 and 2% donor MSCs by
      FISH 60 days after MSC infusion. In four patients with MLD there were significant
      improvements in nerve conduction velocities after MSC infusion. The bone mineral
      density was either maintained or slightly improved in all patients. There was no
      clinically apparent change in patients' overall health, mental and physical
      development after MSC infusion. We conclude that donor allogeneic MSC infusion is
      safe and may be associated with reversal of disease pathophysiology in some
      tissues. The role of MSCs in the management of Hurler syndrome and MLD should be
      further evaluated.

PMID- 12203138
TI  - Vitamin D receptor gene polymorphism associates with graft-versus-host disease
      and survival in HLA-matched sibling allogeneic bone marrow transplantation.
AB  - We investigated the role of polymorphism of the vitamin D receptor (VDR) gene in
      HLA-matched sibling BMT for polymorphisms previously associated with human
      disease pathology. In intron 8 of the VDR gene, the B and A alleles of the BsmI
      and ApaI RFLPs were found to associate with reduced aGVHD when present in the
      patient's genotype. Logistic regression analysis demonstrated that patient VDR
      genotype, along with previously identified IL-10(-1064) and IFN-gamma genotype to
      be risk factors for severe acute GVHD. The A allele also associates with
      increased likelihood of death when present in the donor genotype (AA vs Aa or aa,
      hazard ratio 2.03, P = 0.0232). In patients who received increased prophylaxis
      with multi-agent therapy, patients whose graft was from a donor with an AA
      genotype had a substantially worse survival than patients whose graft was from a
      donor with a non-AA genotype (hazard ratio 12.93, P < 0.0001). Analysis of VDR
      genotype in prospective BMT recipients could indicate patients at risk of severe
      aGVHD. Analysis of VDR genotype in prospective BMT donors may identify
      individuals who have greater transplant-related mortality, and also allow
      appropriately restricted use of increased immunosuppressive prophylaxis.

PMID- 12203139
TI  - Allogeneic bone marrow transplantation in patients with follicular lymphoma: a
      single center study.
AB  - The role of allogeneic BMT for follicular lymphoma remains to be established.
      From 1995 to 2000, 16 patients with follicular lymphoma underwent allogeneic BMT
      at our center. At the time of transplantation, two patients were in complete
      remission, 11 in partial remission and three had refractory disease. Fourteen
      patients were transplanted using a standard myeloablative conditioning regimen
      and two a nonmyeloablative conditioning regimen. With a median follow-up of 1184
      days (range 403-1999 days) after BMT, 11 patients were alive, whereas five died
      of transplant-related mortality. Eight patients remained in CR 284+ to 1022+ days
      (median 560+ days) after BMT. Two patients relapsed 63 and 1073 days after BMT.
      They achieved a further complete remission after salvage treatment and remained
      alive 403 and 1224 days after BMT, respectively. One patient with autologous
      reconstitution had never been in CR after BMT. He was retreated with salvage
      chemotherapy but only achieved CR with subsequent rituximab treatment and was
      still alive, 1999 days after transplantation. The estimated 2-year overall
      survival and event-free survival rates were 68% and 55%, respectively. Age
      greater than 37 years at diagnosis, positive recipient CMV serology and ECOG
      performance status > or =1 at diagnosis were associated with shorter overall
      survival (P = 0.05, P = 0.009 and P = 0.03, respectively). Ann Arbor III-IV stage
      at diagnosis was associated with shorter event-free survival (P < 0.04).
      Allogeneic BMT seems to be effective for patients with follicular lymphoma.
      However, the relatively high rate of early transplant-related mortality
      emphasizes the need to define indications and use prospective protocols involving
      a less toxic transplant procedure.

PMID- 12203140
TI  - High-dose acyclovir and pre-emptive ganciclovir to prevent cytomegalovirus
      disease in myeloablative and non-myeloablative allogeneic stem cell
      transplantation.
AB  - We evaluated high-dose acyclovir and pre-emptive ganciclovir to prevent
      cytomegalovirus disease in myeloablative and non-myeloablative allogeneic stem
      cell transplantation. One hundred and seventy-four consecutive patients who were
      at risk for CMV infection (either recipient or donor seropositive) and received
      either intensive chemoradiotherapy and a T cell-depleted stem cell transplant
      followed by delayed add-back of donor T cells (TCDT: n = 98), or a non
      myeloablative preparative regimen followed by an unmanipulated peripheral blood
      stem cell transplant (NMT: n = 76) from an HLA-identical sibling donor were
      studied. All received high-dose acyclovir (HDACV) from day - 7 for 3 months post
      transplant in conjunction with weekly CMV pp65 antigenemia monitoring and pre
      emptive treatment with intravenous immunoglobulin (not CMV-specific) and
      ganciclovir. The actuarial probabilities of developing pp65 antigenemia were 83
      +/- 4% after TCDT and 41 +/- 6% after NMT (P < 0.00001) with reactivation
      occurring earlier in the TCDT group (the median 36 days vs 55 days). We observed
      no reactivation of CMV in seronegative recipients with a seropositive donor (n =
      23). A total of 11 patients (5 in TCDT, 6 in NMT) developed CMV disease within
      400 days after transplantation, and one death was clearly attributable to CMV
      interstitial pneumonitis (IP). This strategy was associated with effective
      control of CMV antigenemia in the majority of patients and near-complete
      eradication of fatal CMV IP.

PMID- 12203141
TI  - Cost analysis of HLA-identical sibling and voluntary unrelated allogeneic bone
      marrow and peripheral blood stem cell transplantation in adults with acute
      myelocytic leukaemia or acute lymphoblastic leukaemia.
AB  - Allogeneic stem cell transplantation (SCT) is one of the most expensive medical
      procedures. However, only a few studies to date have addressed the costs of HLA
      identical sibling transplantation and only one study has reported costs of
      unrelated transplantation. No recent cost analysis with a proper follow-up period
      and donor identification expenses is available on related or voluntary matched
      unrelated donor (MUD) SCT for adult AML or ALL. Therefore, we calculated direct
      medical (hospital) costs based on 97 adults who underwent HLA-identical sibling
      bone marrow transplantation (BMT) or peripheral blood stem cell transplantation
      (PBSCT), and patients who received a graft from a MUD between 1994 and 1999. The
      average costs per transplanted patient were Euro 98,334 (BMT), Euro 151,754
      (MUD), and Euro 98,977 (PBSCT), including donor identification expenses, 2 years
      follow-up and costs of patients who were not transplanted after they had been
      planned to receive an allograft. The majority of these costs was generated during
      the hospitalisation for graft infusion. For MUD transplants, nearly one-third of
      these costs was spent on the search for a suitable donor. For patients who were
      alive after 2 years, cumulative expenses were calculated to be Euro 103,509
      (BMT), Euro 173,587 (MUD), and Euro 105,906 (PBSCT).

PMID- 12203142
TI  - Acute myocardial ischemia after high-dose therapy with BEAM regimen.
AB  - We describe a case of acute myocardial ischemia following carmustine treatment
      during the BEAM regimen. Despite this, full completion of the autologous
      peripheral stem-cell transplant was possible.

PMID- 12203143
TI  - Bone marrow transplantation in Shwachman-Diamond syndrome.
AB  - Shwachman-Diamond syndrome is a rare autosomal recessive disorder characterized
      by exocrine pancreatic dysfunction, metaphyseal dysostosis and bone marrow
      dysfunction with a predilection towards severe hematologic complications.
      Allogeneic bone marrow transplantation has been used as a therapeutic approach
      for SDS patients with serious hematologic abnormalities with mixed results. There
      is some concern that these patients may be more susceptible to early (<100 days)
      transplant-related complications than other transplant groups. We report a
      patient who received a matched allogeneic transplant without developing serious
      early transplant-related complications, but eventually died from relapse of his
      disease. Although experience is limited, a review of the reported cases suggests
      patients with SDS may be transplanted without significant short-term morbidity
      and mortality.

PMID- 12203144
TI  - Cryptococcal meningitis following autologous stem cell transplantation in a
      patient with multiple myeloma.

PMID- 12203146
TI  - [History of the Mannheim Oststadt Clinic].

PMID- 12203148
TI  - [Distal radius fractures and concomitant lesions. Experimental studies concerning
      the pathomechanism].
AB  - Since Colles (1814) first described a distal radius fracture and the publication
      by Dupuytren (1834), the frequency of and problems surrounding these fractures
      were increasingly recognised. Not only the treatment but also the formation and
      type of fracture were repeatedly analysed. The various theories concerning the
      pathomechanism led to names such as: "tear fracture", "bend fracture", "thrust
      fracture", "compression fracture", "snap fracture" and others. In our
      experimental studies we attempted to simulate the pathomechanism of distal radius
      fractures and present them pictorially. With the help of a materials testing
      machine, 63 prepared cadaver arms were hyperextended in the wrist joint until a
      radius fracture occurred. The concomitant lesions were registered radiologically
      and by dissection. Moreover, additional cadaver arms were deep-frozen and
      examined by means of computer tomography and cryosection according to Kathrein.
      Through experimental hyperextension it was possible to generate dorsal, central,
      and palmar types of fractures. We produced 42 dorsal, 14 central and 7 palmar
      fractures. Fundamentally, it seems that the fracture depends on the extent in
      which the carpal bones of the proximal row are pressed against the dorsal,
      central or palmar part of the articular surface of the distal radius. The
      subsequent dissection showed in 40 cases (63 %) mostly multiple concomitant
      lesions and in 23 cases (37 %) none of these. The reason for concomitant lesions
      may be the proportion of bone stability to the strength of ligaments. Most
      frequently (27 cases, i.e. 43 %), we found a destabilisation of the articular
      disk with or without a bony avulsion fragment (fracture of the ulnar styloid). We
      also commonly found ruptures of the interosseous ligaments between scaphoid and
      lunate (20 cases, i.e. 32 %) and lunate and triquetrum (11 cases, i.e. 18 %). It
      is difficult to apply knowledge gained from experimental studies on preserved
      cadaver arms clinically. There are of course no physiological reflexes and the
      slow fracture process must be taken into consideration. This holds true not only
      for concomitant lesions but also for the type of fracture. On the other hand, in
      these experimental studies it was possible to generate many realistic types of
      fractures with their concomitant lesions.

PMID- 12203149
TI  - [Results of arthroscopic synovialectomy of the wrist].
AB  - In the course of inflammatory rheumatic diseases, isolated synovialitis of the
      wrist and distal radioulnar joint can be found without simultaneous affection of
      the extensor tendons. It may be the only manifestation of the disease in the
      sense of monarthritis or one of few affected sites as in oligoarthritis. With
      modern medical treatment of disease-modifying drugs, this constellation seems to
      be more frequent. In this situation, we rather perform arthroscopic
      synovialectomy than open synovialectomy as long as form and function of the joint
      are maintained. The distal radioulnar joint may also be approached
      arthroscopically through the perforation of the TFCC, which is usually
      encountered. A clinical study was performed to evaluate the results of this
      procedure concerning function, relief of pain, progression of the disease, and
      risk of recurrence. Between 1995 and 2000, 22 patients (15 female, 7 male) with
      an average age of 50 years (range 16 to 74) were operated, in one case both
      wrists. 19 patients have been reexamined clinically and by X-ray after an average
      follow-up of 21 months (range 6 to 57 months), three by telephone interview. The
      results were evaluated according to the Mayo modified wrist score (pain,
      function, motion, and grip-strength related to the contralateral side) and
      compared to the preoperative values. In the case of bilateral affection, the
      score was not applied. Also, the patients' subjective evaluation of the results
      have been taken into account. Progression of the disease has been checked in the
      standard preoperative and postoperative X-rays of the wrist graded according to
      the Larsen scale. Special attention was paid to signs of recurrence. The wrist
      score improved significantly from an average of 40 points preoperatively to 69
      points postoperatively. Eleven patients estimated their wrists as absolutely
      good, nine as improved, two as unchanged compared to the preoperative situation.
      Nine patients reported no pain at all, eleven less pain than before and two no
      change. 17 patients have been satisfied with the procedure, five not.
      Radiographic progression of the disease from the preoperative status (Larsen
      stage 0 to III, exceptionally IV) to postoperative was found in three cases. In
      19 cases there was no progression. Recurrence was noted in six cases after an
      average time of six months; a secondary procedure was necessary in two cases.
      Wrist motion improved in almost all patients from an average value of extension
      plus flexion of 83 degrees preoperatively to 99 degrees postoperatively.
      Conclusion. Arthroscopic synovialectomy of the wrist reduces pain and improves
      function in most cases. It also improves motion, which is an advantage to the
      open procedure. Patient acceptance of the procedure is high.

PMID- 12203150
TI  - [Dislocation of the pisiform bone. A review of the literature].
AB  - Dislocation of the pisiform bone is extremely rare. So far, only 25 cases proved
      by radiographs have been reported. The sturdiness and stability of its
      ligamentous attachments may explain why dislocations of the pisiform are so rare.
      Often the dislocation is the result of direct trauma to the palmar and ulnar
      aspect of the wrist and less frequently due to indirect force or forceful
      muscular contraction. Dislocation of the pisiform bone occurs predominantly in
      young and active males. Usually, the pisiform is dislocated proximally or
      distally. The diagnosis is made by plain radiography. Operative treatment with
      pisiform excision and meticulous reapproximation of the attached soft-tissue
      structures yielded the most reliable results with preservation of wrist-flexion
      strength. Thus, although being very heterogenous with regard to mechanism of
      injury and displacement, pisiform dislocations should receive uniform treatment
      to obtain predictable results.

PMID- 12203151
TI  - [Scapholunate dissociation: treatment by dorsal capsulodesis].
AB  - Between December 1994 and December 1996, 26 patients with a scapholunate ligament
      injury (three with SLD 1. degrees, 16 with SLD 2. degrees and 7 with SLD 3.
      degrees ) underwent an operation for dorsal capsulodesis in the Klinik fur
      Handchirurgie, Bad Neustadt/Saale. Mean follow-up was 24 months (16 to 37
      months). Follow-up criteria were range of motion, grip strength, pain relief, and
      X-ray findings. Clinical outcome was evaluated using a personal questionnaire,
      the DASH- and a modified Cooney-Score. Although significant reduction of joint
      mobility compared to the opposite site was found in all cases (E/F 32 %, U/R 19
      %), the reduction of pain was 30 %. Grip-strength was not altered. Thus, 86 % of
      the patients were satisfied with the result obtained. On X-ray, the scapholunate
      angle was raised in the SLD 3. degrees -group by 12 degrees postoperatively; in
      the group with dynamic instability, X-ray findings were normal. Overall, 19 %
      (5/26) needed further operations due to persistent pain.

PMID- 12203152
TI  - [Denervation of finger joints as an alternative procedure to arthrodesis or
      endoprosthesis].

PMID- 12203153
TI  - [Invited Commentary on the Article of D. Burg, M. In"fanger, C. Meuli-Simmen, Th.
      Stallmach, G. Beer, S. Amgwerd, V. E. Meyer: Methode, Indikation und kritische
      Wertung der intraoperativen Nervenfunktionsdiagnostik].

PMID- 12203155
TI  - [How reliable is the posterior interosseous artery island flap? A review of 88
      patients].
AB  - The distally-based, reverse posterior interosseous flap can be used to
      reconstruct soft-tissue defects in the region of the hand, provided there is an
      intact anastomotic network of the posterior and anterior interosseous system at
      the wrist. Between 1986 and 2000, 88 flap procedures were planned. Anatomical
      variations were recorded in 21 patients (24 %), in five of which the flap could
      not be harvested. In the remaining 16 patients, flap dissection was more
      difficult due to anatomical variations. There was a complication rate of 23 %,
      including haematoma, congestion, infection or technical errors, which resulted in
      flap necrosis of variable degrees in 11 patients (13 %). In case of haematoma,
      flap loss could be reduced by early revision surgery. There was no statistical
      correlation between anatomical variations and complications or flap loss.
      Secondary flap corrections, including defatting and remodelling, were commonly
      performed in due course. Knowing the limitations of the posterior interosseous
      flap, fasciocutaneous flaps are considered ideal to reconstruct soft-tissue
      defects or contractures of the thumb web and the dorsal hand because of good
      tissue matching. Fascial flaps are a good option for palmar defects or to wrap
      around neurolyzed nerves.

PMID- 12203156
TI  - [Continuous free-flap monitoring with tissue-oxygen measurements: experiences of
      the last years].
AB  - Early recognition of flap failure is the prerequisite for flap salvage. Many
      methods are used to monitor free-flaps. The time interval for re-establishing
      vascular patency is the deciding factor for a successful revision. Prompt
      revision surgery and a quick and sufficient correction of the microvascular
      anastomosis are necessary to reestablish flap viability. The aim of this study
      was to evaluate the real impact of this probe as a continuous, precise and
      clinically relevant monitoring system in free-flap surgery. One of our main
      objectives was to create guidelines and "normal" ranges of p ti O 2 -values for
      the uncomplicated use of the Licox Probe in free-flap surgery for the first time.
      The Licox Catheter pO 2 Mikro-Probe instrument is used for continuous
      determination of oxygen partial pressure (pO 2 ) in body fluids and tissue (p ti
      O 2 ). Over a period of more than three years, 70 free tissue-transplantations to
      the head and neck, trunk, and upper and lower extremities were monitored by use
      of the implantable Licox Catheter Probe System. In all patients, a decrease of
      the p ti O 2 -levels was noted during the first minutes, until a more or less
      stable level was reached. At the time of weaning off, the p ti O 2 values
      decreased once again. After approximately 30 minutes, an almost stable but
      reduced p ti O 2 -level was reestablished (34,6 +/- 10,9 mm Hg). During the next
      days, we observed a more or less constant but reduced level. These values from
      the second day on were lower than the mean values of the first day. The mean
      value for all flaps was 23,1 +/- 6,5 mm Hg. Nevertheless, in all cases (10 of 70
      flaps) where the p ti O 2 -level decreased more than 10 mm Hg within a half hour
      period, the flap showed vascular problems on re-exploration. Another clinically
      relevant value that was observed in all flaps with vascular problems was a drop
      of the p ti O 2 -value, below 10 mm Hg. In the cases of arterial thrombosis (2 of
      10 flaps), a rapid decrease was noted. In the cases of venous complications (8 of
      10 flaps), a more or less slow decrease of the p ti O 2 -value was observed.
      These observations may serve as precise indicators for vascular complications and
      flap failure. Based on our observations and data, it seems that the Licox-Probe
      is a sensitive and accurate monitoring system for a variety of free flaps.

PMID- 12203157
TI  - [Plexiform fibrohistiocytic tumour - case report of a rare low-malignant tumour
      with frequent localisation at the upper limb].
AB  - A male child aged nine months was admitted due to a slow growing, painless
      resistance at the palmar aspect of the proximal phalanx of the index finger. The
      intraoperative aspect of the tumour showed a yellow to white soft tissue mass
      with signs of infiltration. After special histopathological stainings, the
      diagnosis of a plexiform fibrohistiocytic tumour was confirmed. In literature
      almost 100 cases were reported since first description by Enzinger and Zhang in
      1988. In this paper, 41 of 65 described cases showed tumour localization in the
      upper limb. This is the second case ever published in Germany and the first with
      localisation to the hand. There is very little clinical experience with this
      tumour entity. Local recurrence, lymphatic and pulmonal metastases with lethal
      outcome in rare cases are described. In the presented case, after secondary
      radical excision of the tumour, the patient has been free of local recurrence and
      actually in complete remission for 14 months.

PMID- 12203158
TI  - [Free microvascular transplantation of the proximal interphalangeal joint for
      primary reconstruction of the metacarpophalangeal joint].

PMID- 12203159
TI  - Role of cat-scratch disease in lymphadenopathy in the head and neck.
AB  - Bartonella henselae is the causative agent of cat-scratch disease (CSD), which
      usually manifests as acute regional lymphadenopathy. The causes of cervical
      lymphadenopathy, with special regard to CSD, were investigated in a study of 454
      patients who presented with unclear masses in the head and neck from January 1997
      through January 2001. Sixty-one patients (13.4%) experienced CSD; 54 (11.9%) had
      primary lymphadenopathy due to other infectious agents, and 41 (9.0%) had
      lymphadenopathy that occurred in association with primary infections of other
      organs. For 171 patients (37.7%), the cause of the cervical lymph node
      enlargement could not be found. B. henselae DNA was detected in extirpated lymph
      nodes only during the first 6 weeks of lymphadenopathy, which indicates that the
      results of polymerase chain reaction strongly depend on the duration of illness.
      CSD should be included in the differential diagnosis of adenopathy in the
      otorhinolaryngologic patient population, to avoid unnecessary treatment.

PMID- 12203160
TI  - Tickborne encephalitis in an area of high endemicity in lithuania: disease
      severity and long-term prognosis.
AB  - Of 250 consecutively admitted patients with central nervous system (CNS)
      infections who were treated during a 1-year period, all 133 patients with
      tickborne encephalitis (TBE) were included in a prospective follow-up study. TBE
      presented as mild (meningeal) in 43.6% of patients and as moderate or severe
      (encephalitic) in 43.6% and 12.8% of patients, respectively. Paralytic disease
      was observed in 3.8% of the subjects, and cranial nerve injury was observed in
      5.3%. One patient died of TBE. Permanent CNS dysfunction after 1 year was found
      in 30.8% of patients; in 8.5% of all TBE cases, severe disabilities required
      adjustment of daily activities. Corticosteroid treatment did not seem to improve
      outcome. A progressive course of TBE was noted in 2 patients. The risk of
      incomplete recovery was significantly higher among patients with the encephalitic
      form of TBE (odds ratio, 4.066; 95% confidence interval, 1.848-8.947). In
      conclusion, TBE is an important pathogen in CNS infection in the Kaunas region of
      Lithuania, and it causes long-lasting morbidity in one-third of cases.

PMID- 12203161
TI  - Aspergillosis: The most common community-acquired pneumonia with gram-negative
      Bacilli as copathogens in stem cell transplant recipients with graft-versus-host
      disease.
AB  - We retrospectively reviewed all cases of pneumonia that required hospitalization
      among allogeneic hematopoietic stem cell transplant (HSCT) recipients with graft
      versus-host disease (GVHD) during the period of January 1996 through July 1999.
      Twelve patients were identified among 88 allogeneic HSCT recipients. All had
      chronic GVHD and were receiving corticosteroid therapy. Ten of the 12 patients
      had pulmonary aspergillosis (PA). For 6 of these 10 patients, a gram-negative
      bacterial pathogen was concurrently isolated from respiratory specimens. At least
      one-half of the patients with PA had an initial presentation suggestive of
      bacterial pneumonia; PA was only suspected on the basis of chest CT findings.
      Aspergillosis is the most common cause of community-acquired pneumonia among
      allogeneic HSCT recipients with GVHD. CT must be used to exclude an underlying
      fungal cause in patients who present with a gram-negative pneumonia.

PMID- 12203162
TI  - Population-based surveillance for postpartum invasive group a streptococcus
      infections, 1995-2000.
AB  - Estimates of disease burden and data on the sources of invasive postpartum group
      A streptococcus (GAS) infections will help guide public health action. Active,
      population-based surveillance was conducted in 9 regions from 1995 through 2000.
      A case of GAS infection was defined as isolation of GAS from a sterile site in a
      resident of a surveillance area who was pregnant or in the postpartum period.
      Census and live birth data were used to calculate rates. Eighty-seven cases of
      postpartum GAS infection (2.2% of 3957 invasive GAS infections) occurred at 3%-8%
      of hospitals annually. We estimate that 220 cases occurred annually in the United
      States. Two or more cases were noted during 6 months at 8 hospitals, during 1
      year at 13 hospitals, and during 2 years at 16 hospitals. Cases due to identical
      emm types clustered more frequently than expected by chance. Although postpartum
      GAS infections are rare, the clustering of infections due to identical strains
      suggests that some invasive cases may have a common source and, therefore, may be
      preventable.

PMID- 12203163
TI  - Strains of Staphylococcus aureus obtained from drug-use networks are closely
      linked.
AB  - Drug users have a higher incidence of colonization with Staphylococcus aureus
      than does the general population, and, as a result, they are at increased risk of
      infection with their colonizing strain. The purpose of this study was to examine
      the role of drug-use risk networks in S. aureus transmission, the similarity of
      S. aureus isolates within these networks, and the possible role of inhalation
      drug use paraphernalia in the transmission of S. aureus. Strains of S. aureus are
      shared among colonized inhalation drug users within drug-use risk networks. It
      suggests that patterns of drug use and the geographic location where drug sharing
      occurs are major contributors to the transfer of staphylococci and, as a result,
      to the high prevalence of staphylococcal colonization and perhaps disease in this
      population.

PMID- 12203164
TI  - Prospective evaluation of a model of prediction of invasive bacterial infection
      risk among children with cancer, fever, and neutropenia.
AB  - A risk prediction model for invasive bacterial infection (IBI) was prospectively
      evaluated among children presenting with cancer, fever, and neutropenia. The
      model incorporated assessment of 5 previously identified risk factors: serum
      level of C-reactive protein (CRP) >/=90 mg/L, hypotension, identification of
      relapse of leukemia as the cancer type, platelet count of </=50,000
      platelets/mm(3), and recent receipt of chemotherapy [16]. Children were uniformly
      evaluated at enrollment and were classified as having high or low risk for IBI
      according to a model that considers the number and type of variables present. Of
      the 263 febrile episodes evaluated during a 17-month period, 140 (53%) were in
      IBI-positive children. The sensitivity, specificity, and positive and negative
      predictive values of the model were 92%, 76%, 82%, and 90%, respectively.
      Identification of these 5 risk factors during the first 24 h of hospitalization
      was helpful in discriminating between children with a high or low risk for IBI.

PMID- 12203165
TI  - Bartonella quintana Bacteremia among Homeless People.
AB  - Bartonella quintana infections have recently reemerged, predominantly among the
      homeless populations in cities in both Europe and the United States. B. quintana
      can cause trench fever, endocarditis, and chronic bacteremia; the human body
      louse is the only known vector. Homeless people who presented to the emergency
      departments of University Hospital in Marseilles, France, were studied, as were
      those who had been admitted to other medical facilities in the city since 1
      January 1997. Samples of blood and body lice were collected for culture for B.
      quintana and for serological testing. Bartonella bacteremia was associated with
      sweats, evidence of louse infestation, serological tests that were positive for
      B. quintana, and high titers of B. quintana antibody. Bacteremia was also
      associated with being homeless for <3 years. Asymptomatic, prolonged bacteremia
      (duration, up to 78 weeks) and intermittent bacteremia were found to occur. Data
      obtained regarding antibiotic regimens showed that treatment with gentamicin and
      doxycycline was effective in preventing relapses of bacteremia.

PMID- 12203166
TI  - Adjunctive intracolonic vancomycin for severe Clostridium difficile colitis: case
      series and review of the literature.
AB  - Successful treatment of severe Clostridium difficile colitis has been reported
      with the use of adjunctive intracolonic vancomycin (ICV) therapy. We report a
      descriptive case series and review the literature on patients with C. difficile
      colitis who received adjunctive ICV therapy. Nine patients received antibiotics
      within 6 weeks prior to presentation. Complete resolution of the clinical
      presentation occurred in 8 patients (88.9%), and eradication of C. difficile
      cytotoxin production was documented in 3 (75%) of 4 patients who were tested
      after the completion of adjunctive ICV therapy. One patient (11.1%) died as a
      result of progressive multisystem organ failure. In the 6 weeks after the
      completion of treatment for C. difficile colitis, no patient had recurrent
      disease, required surgical intervention, or experienced complications from
      adjunctive ICV therapy. In this case series, administration of adjunctive ICV
      therapy appeared to be a safe, practical, and effective adjunctive therapy for
      severe C. difficile colitis.

PMID- 12203167
TI  - Hospital-acquired pneumococcal bacteremia.
AB  - To assess the most relevant features of hospital-acquired pneumococcal
      bacteremia, all cases of pneumococcal bacteremia at a single teaching hospital
      that occurred during 1988-2000 were prospectively studied. During this period,
      374 cases of pneumococcal bacteremia were documented; 39 (10%) of these episodes
      were hospital acquired. Twenty-nine (74%) cases occurred during the period of
      December through May. Eleven (28%) of 39 patients had received antimicrobial
      agents in the month before the onset of bacteremia. All patients had underlying
      diseases that predisposed them to pneumococcal infection. The most common origin
      of infection was the respiratory tract, followed by the intra-abdominal region.
      Fifteen strains were fully susceptible to penicillin, and 20 were intermediately
      resistant. Only 25 strains were susceptible to erythromycin; all strains that
      were resistant to erythromycin were penicillin nonsusceptible. Eighteen (46%) of
      39 patients died; the mortality rate related to infection was 39%.

PMID- 12203168
TI  - Influence of cytomegalovirus seropositivity on outcome after T cell-depleted bone
      marrow transplantation: contrasting results between recipients of grafts from
      related and unrelated donors.
AB  - We analyzed the effect of cytomegalovirus (CMV) serostatus on overall survival
      (OS) and transplant-related mortality (TRM) in 253 consecutively treated patients
      receiving partially T cell-depleted (TCD) bone marrow from either matched related
      donors (MRDs; n=205) or matched unrelated donors (MUDs; n=48). Short-course, low
      dose preemptive therapy with ganciclovir was provided as soon as a positive
      antigenemia assay result was obtained. Ganciclovir prophylaxis, which was
      identical to preemptive therapy, was given to patients with acute graft-versus
      host disease (GVHD) grades II-IV who had to be treated with high-dose steroids.
      In recipients of transplants from MRDs, inferior OS and increased TRM were
      predicted by extensive chronic GVHD (P<.001). High-risk disease status and older
      age adversely influenced OS (P=.001) and TRM (P=.002), respectively; older age
      resulted in a trend toward decreased OS (P=.066). In recipients of transplants
      from MUDs, OS and TRM were strongly influenced by patient CMV seropositivity
      (P=.013 and.007, respectively). In conclusion, CMV seropositivity is not an
      adverse risk factor for OS and TRM in recipients of transplants from MRDs.
      However, in recipients of transplants from MUDs, patient CMV seropositivity
      strongly affects OS and TRM.

PMID- 12203169
TI  - A legacy in 20th-century medicine: Robert Allan Phillips and the taming of
      cholera.
AB  - The legacy of Captain Robert Allan Phillips (1906-1976) was to establish
      effective, evidence-based rehydration methods for the treatment of cholera. As a
      Navy Lieutenant at the Rockefeller Institute for Medical Research (New York, New
      York) during World War II, Phillips developed a field method for the rapid
      assessment of fluid loss in wounded servicemen. After the war, he championed the
      establishment of United States Naval Medical Research Unit (NAMRU)-3 (Cairo;
      1946) and NAMRU-2 (Taipei; 1955), serving at the helm of both units. Phillips
      embarked on cholera studies during the 1947 Egyptian cholera epidemic and brought
      them to maturity at NAMRU-2 (1958-1965), elucidating the pathophysiologic
      derangements induced by cholera and developing highly efficacious methods of
      intravenous rehydration. His conception of a simpler cholera treatment was
      realized in the late 1960s with the development of glucose-based oral rehydration
      therapy, a monumental breakthrough to which many other investigators made vital
      contributions. Today, these simple advances have been integrated into everyday
      medical practice across the globe, saving millions of lives annually.

PMID- 12203170
TI  - The battle against emerging antibiotic resistance: should fluoroquinolones be
      used to treat children?
AB  - Inappropriate use of antibiotic drugs in humans and animals has led to widespread
      resistance among microbial pathogens. Resistance is the phenotypic expression
      corresponding to genetic changes caused by either mutation or acquisition of new
      genetic information. In some cases, multidrug resistance occurs. Streptococcus
      pneumoniae is one of the most important respiratory pathogens, playing a major
      role in both upper and lower respiratory tract infections. Pneumococcal
      resistance to antimicrobials may be acquired by means of horizontal transfer
      followed by homologous recombination of genetic material from the normal flora of
      the human oral cavity or by means of mutation. Resistance to penicillins and
      macrolides has been increasing for some time, but, recently, fluoroquinolone
      resistance has become an issue as well. We are concerned that, if
      fluoroquinolones are approved for use in children, their widespread use will
      result in rapid emergence of pneumococcal resistance, because children are more
      often colonized in the nasopharynx with high-density populations of pneumococci
      than are adults.

PMID- 12203171
TI  - Current strategies for management of influenza in the elderly population.
AB  - Influenza virus remains among the most important pathogens infecting elderly
      people. Vaccination is the most cost-effective strategy to reduce morbidity and
      mortality due to influenza. For persons who are not vaccinated or for whom
      vaccines fail to prevent influenza, there are 2 classes of efficacious drugs for
      treatment or chemoprophylaxis: M2 channel inhibitors and neuraminidase
      inhibitors. Effective treatment, however, must commence within 48 h of the onset
      of symptoms, which can create problems for patients who wait to see whether their
      symptoms worsen or improve. Older adults who have relocated to the congregate
      housing environments of assisted living and long-term care facilities deserve
      special consideration, because influenza exposure risks are different for this
      group. Strategies for control of influenza must combine preventive approaches,
      such as vaccination, educational approaches, and the introduction of policies
      that allow health care professionals anticipate, identify, and efficiently
      respond to influenza outbreaks.

PMID- 12203172
TI  - Emerging epidemiology of bat-associated cryptic cases of rabies in humans in the
      United States.
AB  - In the United States, during the past half-century, the number of humans to die
      of rabies dramatically decreased to an average of 1-2 per year. Although the
      number of deaths is low, most deaths occur because individuals are unaware that
      they had been exposed to and infected with rabies virus, and, therefore, they do
      not seek effective postexposure treatment. Molecular epidemiological studies have
      linked most of these cryptic rabies exposures to rabies virus variants associated
      with insectivorous bats. In particular, virus variants associated with 2
      relatively reclusive species, the silver-haired bat (Lasionycteris noctivagans)
      and the eastern pipistrelle (Pipistrellus subflavus), are the unexpected culprits
      of most cryptic cases of rabies in humans.

PMID- 12203173
TI  - Foodborne viral gastroenteritis: challenges and opportunities.
AB  - Norwalk-like viruses (NLVs) are estimated to be the most common causes of
      foodborne disease in the United States, accounting for two-thirds of all food
      related illnesses. The epidemiologic features and disease burden associated with
      NLVs have, until recently, been poorly understood because of the lack of
      sensitive detection assays and the underuse of available diagnostic tools.
      However, the application of molecular techniques to diagnose and investigate
      outbreaks of infection during recent years has led to a growing appreciation of
      the importance of these agents. NLVs are a principal cause of outbreaks of acute
      onset vomiting and diarrhea in all age groups-most commonly, via contamination of
      uncooked foods by infected foodhandlers, but also via foods contaminated at their
      sources, such as oysters and raspberries. NLVs may also account for >10% of
      sporadic cases of gastroenteritis in children and adults. Future research will
      focus on the development of easy-to-use diagnostic assays based on antigen and
      antibody detection as well as vaccine development. Implementation of simple
      prevention measures, including correct food-handling practices, will continue to
      be a priority.

PMID- 12203174
TI  - Hepatitis C information on the world wide web.
AB  - World Wide Web sites about hepatitis C vary from simple Web sites that provide
      basic information to the layperson to regularly updated medical-information
      portals. Medical professionals can use these Web sites to obtain up-to-date
      information on the epidemiological characteristics of hepatitis C and treatment
      of and information materials for their patients. For researchers in this field,
      there are Web sites that provide bibliographies, conference summaries and
      updates, and continuing medical education credits. This review provides an
      overview of selected Web sites for health care providers and researchers, sites
      of professional societies, sites created by patients, and sites created by the
      pharmaceutical industry.

PMID- 12203175
TI  - Effects of formulation and dosing strategy on amprenavir concentrations in the
      seminal plasma of human immunodeficiency virus type 1-infected men.
AB  - We compared seminal plasma pharmacokinetic data for the investigational
      amprenavir prodrug GW433908 with those for amprenavir and an amprenavir-ritonavir
      combination regimen. All 3 regimens resulted in detectable blood plasma and
      seminal plasma concentrations of amprenavir. The majority of these concentrations
      were greater than the plasma protein-corrected 50% inhibitory concentration for
      wild-type human immunodeficiency virus type 1.

PMID- 12203176
TI  - Disappearance of trachoma from Western Nepal.
AB  - We assessed how much of the observed decline in the prevalence of trachoma in a
      district of Western Nepal was due to an antibiotic treatment program and how much
      to an underlying secular trend outside of the program. Although antibiotic
      treatments clearly have an effect at 6 months, we were unable to show that this
      effect persisted at 12 months; in fact, long-term gains may be due to a secular
      trend in the area.

PMID- 12203178
TI  - Discrepant results of 2 screening tests for anti-HIV antibody.

PMID- 12203177
TI  - A randomized, double-blind, placebo-controlled trial of acetazolamide for the
      treatment of elevated intracranial pressure in cryptococcal meningitis.
AB  - We conducted a trial of oral acetazolamide for the treatment of cryptococcal
      meningitis in 22 Thai adults with headache and an opening cerebrospinal fluid
      pressure of >/=200 mm H(2)0. The trial was terminated prematurely because
      patients who received acetazolamide developed significantly lower venous
      bicarbonate levels and higher chloride levels and had more-frequent serious
      adverse events than did subjects who received placebo.

PMID- 12203180
TI  - Indications for surgery for elderly patients with infective endocarditis.

PMID- 12203181
TI  - A case of necrotizing fasciitis due to Streptococcus pneumoniae following topical
      administration of nonsteroidal anti-inflammatory drugs.

PMID- 12203182
TI  - Clusters of cases of invasive aspergillosis in transplant units: nosocomial
      spread or enhanced virulence?

PMID- 12203183
TI  - Efavirenz-associated severe hyperlipidemia.

PMID- 12203184
TI  - Eosinophilic meningitis due to Angiostrongylus cantonensis.

PMID- 12203185
TI  - Prolonged candidemia in patients with cancer.

PMID- 12203186
TI  - Pythium insidiosum pleuropericarditis complicating pneumonia in a child with
      leukemia.
AB  - We describe a 12-year-old boy with acute myeloid leukemia who developed
      pleuropericarditis while he was neutropenic and was receiving intravenously
      administered antibiotic and antifungal therapy for pneumonia. A KOH preparation
      of the purulent material from an extensive diagnostic and therapeutic
      pleuropericardial drainage procedure revealed multiple irregularly septate
      hyphae, and cultures yielded the organism Pythium insidiosum. After completing a
      12-month course of intravenously administered liposomal amphotericin B (AmBisome;
      Fujisawa Healthcare) and itraconazole, the patient remained alive, in clinical
      remission, and symptom free.

PMID- 12203187
TI  - Concurrent fecal colonization with extraintestinal pathogenic Escherichia coli in
      a homosexual man with recurrent urinary tract infection and in his male sex
      partner.
AB  - A 72-year-old homosexual man experienced frequent recurrences of symptomatic
      urinary tract infection (UTI) putatively due to the same strain of
      extraintestinal pathogenic Escherichia coli, despite receiving repeated courses
      of seemingly appropriate antibiotic therapy. Both the patient and his male sex
      partner were found to have fecal colonization with the strain recovered from the
      patient's urine, which exhibited characteristics of the E. coli O1/O2:K1:H7
      clonal group (which is associated with urosepsis), whereas genetically distinct
      E. coli strains were recovered from a jar of petroleum jelly used by the couple
      during sexual activity.

PMID- 12203188
TI  - Exogenous cushing syndrome mimicking human immunodeficiency virus lipodystrophy.
AB  - A 45-year-old man infected with human immunodeficiency virus (HIV) developed
      abnormal fat accumulations that initially were believed to be caused by HIV
      lipodystrophy. Further clinical evaluation revealed, however, that the patient
      had developed exogenous Cushing syndrome, which presumably was caused by the
      inhibition of CYP3A4's metabolism of inhaled fluticasone by the protease
      inhibitor ritonavir. Clinicians should be aware that clinical clues may indicate
      conditions other than lipodystrophy that may cause abnormal fat accumulation and
      that fluticasone should be cautiously administered to patients who are receiving
      ritonavir.

PMID- 12203189
TI  - How do personal values influence health care?

PMID- 12203190
TI  - Parents' views of their children's participation in phase I oncology clinical
      trials.
AB  - Data from two descriptive studies regarding decision making in pediatric oncology
      were analyzed using qualitative, secondary analysis techniques to describe how
      parents view their children's participation in phase I oncology clinical trials.
      A conceptual framework on family management styles (defining, managing, and
      consequence themes) was used as an organizational framework to analyze the
      available parental data. Parents defined or viewed their situation in
      relationship to their choices and expectations, health care provider
      expectations, children's illness situation, and family and personal situations.
      These themes are contrasted to clinical, parental, and ethical perspectives from
      the literature to make recommendations for further research emphasizing the
      concerns of families.

PMID- 12203191
TI  - Development and implementation of a carboplatin desensitization protocol for
      children with neurofibromatosis, type 1 and hypersensitivity reactions in an
      outpatient oncology clinic.
AB  - Neurofibromatosis, type 1 (NF 1), is a relatively common disorder. Children with
      NF 1 are at much greater risk for the development of optic pathway tumors, which
      are sometimes treated with chemotherapy. As a result, many oncology centers and
      clinics are now seeing and treating NF patients. One of the most frequently used
      drugs is carboplatin. However, as many as 30% of NF patients may develop a
      reaction to carboplatin, which can include anaphylaxis. This often results in the
      cessation of the medication and treatment protocol. At the Children's Hospital of
      Philadelphia a desensitization protocol has been instituted with children who
      have had such reactions and whose tumors have demonstrated a positive response to
      the treatment. The desensitization process is quite complex and requires an
      interdisciplinary approach. However, it is the nursing personnel that are key to
      the successful coordination and delivery of such a protocol in an oncology
      outpatient clinic on a regular basis.

PMID- 12203192
TI  - Promoting parental use of distraction and relaxation in pediatric oncology
      patients during invasive procedures.
AB  - Treatment of children with cancer involves many painful procedures. Invasive
      procedures such as bone marrow aspiration and lumbar punctures can be very
      traumatic, painful, and anxiety-producing for both parents and child. The use of
      distraction and relaxation techniques is a nonpharmacologic strategy to promote
      comfort and decrease anxiety and procedural pain. This article describes the
      development of a parent education booklet that promotes the use of distraction
      and relaxation techniques during invasive procedures across pediatric oncology
      inpatient and outpatient settings. Promoting parents' use of these techniques
      with their child can add to the parent and child's repertoire of coping skills
      that can be used throughout the course of their treatment or during other painful
      procedures. These techniques in combination with traditional methods of practice
      enhance quality patient care and significantly decrease the cost and risk
      associated with performing these procedures under general anesthesia.

PMID- 12203194
TI  - What is a moral dilemma and what would you do if you were faced with one?

PMID- 12203193
TI  - A living legend in pediatric oncology nursing: Gail Perin.

PMID- 12203195
TI  - A long road home.

PMID- 12203196
TI  - Introduction: emerging therapies derived from the molecular pathogenesis of
      secondary hyperparathyroidism in ESRD patients.

PMID- 12203197
TI  - Pathogenesis of parathyroid dysfunction in end-stage renal disease.
AB  - The parathyroid functions to maintain normal calcium and phosphate homeostasis
      and is central to normal bone physiology. In end-stage renal disease (ESRD),
      there is a failure of these normal homeostatic mechanisms with the frequent
      development of secondary hyperparathyroidism, which contributes to the
      pathogenesis of renal bone disease. The phosphate retention of ESRD, together
      with the reduced serum calcium and 1,25-dihydroxycholecalciferol vitamin D(3)
      (1,25[OH](2)D(3)) concentrations are the known factors that determine the
      progression to secondary hyperparathyroidism. 1,25(OH)(2)D(3) markedly decreases
      parathyroid hormone (PTH) gene transcription, whereas the effects of calcium and
      phosphate are on PTH mRNA stability, PTH secretion, and parathyroid cell
      proliferation. The mechanisms of these effects are discussed in this review.

PMID- 12203198
TI  - Vitamin D receptor-mediated gene regulation mechanisms and current concepts of
      vitamin D analog selectivity.
AB  - Lipophilic hormones of steroidal origin such as the sex hormones and 1,25
      dihydroxy vitamin D(3) (1,25[OH](2)D(3)) function by regulating patterns of gene
      expression in cells. The mediators of such actions are nuclear receptors that
      recognize these ligands with high affinity and selectivity and function through
      several mechanisms as gene specific transcription factors. As a result of the
      mechanistic complexity of nuclear receptor action, recent studies have revealed
      that both synthetic analogs as well as novel mimetics of a receptor's natural
      hormonal ligand are capable of modulating functional responses in both cell- and
      gene-selective manners. These findings have given rise to the term selective
      receptor modulators, typified by such synthetic estrogen receptor ligands as
      tamoxifen and raloxifene. A number of vitamin D analogs have been prepared that
      appear to exhibit tissue-selective activity--most notable through their inability
      to induce levels of hypercalcemia typical of the activity of the natural hormone
      1,25(OH)(2)D(3). Because this debilitating yet normal feature of the natural
      ligand limits its usefulness in a variety of clinical indications, including its
      application to prevent bone disease caused by secondary hyperparathyroidism, this
      feature of many of the new analogs is especially welcome. This article discusses
      what constitutes a selective receptor modulator and whether the current vitamin D
      analogs represent such entities.

PMID- 12203199
TI  - Use of vitamin D analogs in chronic renal failure.
AB  - Renal osteodystrophy is the term used to describe the spectrum of bone diseases
      associated with chronic renal failure. Deficiency of 1,25
      dihydroxycholecalciferol (calcitriol) plays a major role in the development of
      renal osteodystrophy, in particular the evolution of secondary
      hyperparathyroidism. In recent decades, our understanding of the complex
      interactions between calcium, phosphorus, vitamin D, and parathyroid hormone
      (PTH) has increased, resulting in a rational approach to therapy in which vitamin
      D analogs have become an essential component. The initial vitamin D analogs that
      have been in widespread clinical use include calcitriol (1,25-[OH](2)D(3)) and
      alfacalcidol (1alpha-[OH]D(3)). These agents have been extensively studied to
      optimize their effects on secondary hyperparathyroidism. The occurrence of
      significant hypercalcemia and hyperphosphatemia limiting their use has led to the
      development of alternative vitamin D analogs that effectively reduce PTH
      secretion without causing these complications. Recently, 3 such analogs, 22-oxa
      1,25-(OH)(2)D(3) (OCT), 1alpha-(OH)D(2) (doxercalciferol), and 19-nor-1,25
      (OH)(2)D(2) (paricalcitol), have been released for clinical use. Only
      paricalcitol has been studied in comparative human clinical trials with
      calcitriol in dialysis patients. Preliminary findings suggest a clinical
      advantage over calcitriol, however, analysis of the larger comparative studies
      are forthcoming.

PMID- 12203200
TI  - Hyperphosphatemia in end-stage renal disease.
AB  - Hyperphosphatemia occurs universally in end-stage renal disease (ESRD) unless
      efforts are made to prevent positive phosphate balance. Positive phosphate
      balance results from the loss of renal elimination of phosphate and continued
      obligatory intestinal absorption of dietary phosphate. Increased efflux of
      phosphate from bone because of excess parathyroid hormone-mediated bone
      resorption can also contribute to increased serum phosphate concentrations in the
      setting of severe hyperparathyroidism. It is important to treat hyperphosphatemia
      because it contributes to the pathogenesis of hyperparathyroidism, vascular
      calcifications, and increased cardiovascular mortality in ESRD patients.
      Attaining a neutral phosphate balance, which is the key to the management of
      hyperphosphatemia in ESRD, is a challenge. Control of phosphorus depends on its
      removal during dialysis and the limitation of gastrointestinal absorption by
      dietary phosphate restriction and chelation of phosphate. Knowledge of the
      quantitative aspects of phosphate balance is useful in optimizing our use of
      phosphate binders, dialysis frequency, and vitamin D sterols. The development of
      new phosphate binders and efforts to find new ways to inhibit gastrointestinal
      absorption of phosphate will lead to improvements in the control of serum
      phosphate levels in ESRD.

PMID- 12203201
TI  - Secondary hyperparathyroidism and its therapy as a cardiovascular risk factor
      among end-stage renal disease patients.
AB  - Secondary hyperparathyroidism (HPTH) was initially viewed as a disorder of the
      skeletal system; however, recent population-based data have associated markers of
      HPTH with an increased cardiovascular mortality among patients with end-stage
      renal disease (ESRD). This has stimulated much interest in further evaluating
      secondary HPTH as a cardiovascular disease risk factor, as well as the putative
      role of its therapy. This article explores the current state of scientific
      evidence concerning the pathophysiology of cardiovascular disease among the ESRD
      population and potential risk factors for its development, including markers of
      HPTH, and its therapies.

PMID- 12203202
TI  - Future role of calcimimetics in end-stage renal disease.
AB  - Calcimimetic agents are small organic molecules that act as allosteric activators
      of the calcium-sensing receptor. In parathyroid cells, they lower the threshold
      for receptor activation by extracellular calcium ions and diminish parathyroid
      hormone (PTH) secretion. These compounds offer a novel way of controlling excess
      PTH secretion in clinical disorders associated with excess PTH secretion,
      including secondary hyperparathyroidism due to chronic renal failure. The first
      calcimimetic agent to be evaluated in clinical trials was R-568, but studies were
      discontinued because of its limited bioavailability and inconsistent
      pharmacokinetic profile. Extensive assessments are currently underway by using a
      second-generation calcimimetic compound, AMG 073, to treat secondary
      hyperparathyroidism. Work completed thus far has shown that AMG 073 effectively
      lowers plasma PTH, without increasing values for the calcium-phosphorus ion
      product in serum in patients with end-stage renal disease. Indeed, serum
      phosphorus levels often decline as plasma PTH levels fall during treatment.
      Recent experimental evidence also suggests that calcimimetic agents may impede
      the development of parathyroid gland hyperplasia, an integral component of
      secondary hyperparathyroidism due to chronic renal failure. Calcimimetics agents
      have considerable potential therefore as a new approach to the medical management
      secondary hyperparathyroidism.

PMID- 12203203
TI  - Surgical management of secondary hyperparathyroidism.
AB  - Most patients with renal failure maintained on chronic dialysis have elevated
      parathyroid hormone (PTH) levels and PTH-mediated bone disease (secondary
      hyperparathyroidism [sHPT]). Elevated PTH production in this setting represents a
      progressive, exaggerated physiologic response to hypocalcemia by the parathyroid
      glands, and generalized growth of the parathyroids is an adaptive response to
      chronic stimulation. Effective medical strategies to reduce PTH secretion and PTH
      mediated bone turnover in sHPT (eg, controlling hyperphosphatemia, normalizing
      serum calcium, and administering vitamin D analogs) has decreased the need for
      parathyroidectomy in recent years. However, failure of medical therapy because of
      inadequate treatment, persistent hyperphosphatemia, or acquired parathyroid
      neoplasia still leads to recommendations for parathyroidectomy in select
      patients. Furthermore, increased awareness of potential long-term, irreversible
      cardiovascular effects of uncorrected hyperparathyroidism has led some to
      advocate parathyroidectomy earlier in the course of this disease. This monograph
      will review parathyroidectomy for secondary and tertiary hyperparathyroidism.

PMID- 12203205
TI  - The health assurance coaching model for chronic renal disease management.

PMID- 12203206
TI  - A view from the La-Z-Boy chair.

PMID- 12203207
TI  - Professionalism in pathology.

PMID- 12203208
TI  - Ethical and professional issues in pathology: a survey of current issues and
      educational efforts.
AB  - Professionalism, including ethics, has assumed greater importance in residency
      education, and the Accreditation Council for Graduate Medical Education now
      requires its incorporation into residency training. Insight into current ethics
      education, as well as those ethical issues important to pathology, would be
      efficacious. A mail survey was sent to all members of the Association of
      Pathology Chairs that asked for specific information related to pathology
      resident education in ethics and identification of important ethical issues in
      the current practice of pathology. A total of 148 surveys were mailed, and 53
      (35.8%) were returned. Formal instruction in ethics is provided by approximately
      62% of pathology residency training programs, and 94% provide informal ethics
      education. However, 84% of programs believed that ethical issues were
      underrecognized, and 38% believed that current ethics training was inadequate.
      Issues regarding the use of tissue for research, confidentiality and privacy, and
      professionalism were identified as the most important ethical issues currently
      encountered in pathology.

PMID- 12203209
TI  - Severe chronic renal failure in association with oxycodone addiction: a new form
      of fibrillary glomerulopathy.
AB  - A number of well-documented renal lesions have been associated with intravenous
      drug use. Recently, investigators reported three cases of granulomatous
      glomerulonephritis in association with intravenous injection of oxycodone
      suppositories. We report 2 patients with similar glomerular pathology who
      presented with chronic renal failure. However, we also highlight the widespread
      tubulointerstitial involvement in this renal lesion. The fibrillar deposits seen
      within the glomeruli and extensively within tubular basement membranes on
      electron microscopy do not have the staining characteristics of amyloid and are
      not associated with immunoglobulin (Ig) deposition. Is this a new form of non-Ig
      associated fibrillary glomerulopathy with its pathogenesis linked to some
      component of the oxycodone suppositories? One of the patients had a history of
      narcotic addiction but denied intravenous injection of suppositories. In both
      patients there was progressive deterioration of renal function with 1 patient
      requiring dialysis within 3 months of initial presentation.

PMID- 12203210
TI  - Pityriasis lichenoides: a clonal T-cell lymphoproliferative disorder.
AB  - Pityriasis lichenoides (PL) is a papulosquamous disorder often considered a form
      of reactive dermatosis and classified with small plaque parapsoriasis (digitate
      dermatosis). However, some patients with PL have developed large plaque
      parapsoriasis (LPP) and mycosis fungoides (MF), and lymphoid atypia and T-cell
      clonality have been reported in lesions of PL. We set out to explore the
      possibility that PL is a form of T-cell dyscrasia. Cases were selected by natural
      language search from an outpatient dermatopathology database; 35 cases were
      reviewed and clinicians and patients were contacted. Hematoxylin and eosin
      stained sections were examined and immunophenotyping was carried out on paraffin
      embedded, formalin-fixed tissue using antibodies to CD2, CD3, CD4, CD5, CD7, CD8,
      CD20, CD30, and CD56. In paraffin-embedded tissue, T-cell receptor (TCR)-gamma
      chain rearrangement was sought through polymerase chain reaction single stranded
      conformational polymorphism analysis. There were 14 males and 21 females with a
      mean age of 40 years held clinically to have PL chronica (PLC) (28 cases) and/or
      PL et varioliformis acuta (PLEVA) (7 cases). Five patients developed large
      atrophic poikilodermatous and/or annular plaques compatible with MF and/or LPP in
      a background of typical PLC. All biopsies showed tropism of lymphocytes to an
      epidermis manifesting psoriasiform hyperplasia, dyskeratosis, parakeratosis, and
      intraepithelial collections of Langerhans' cells and lymphocytes mimicking
      Pautrier's microabascesses. Epidermal atrophy, dermal fibroplasia,
      poikilodermatous alterations, and a dominance of intraepidermal cerebriform cells
      were seen only in patients with chronic persistent disease (i.e., PLC) and in
      some cases corresponded with clinical progression to MF. All cases had a T cell
      dominant infiltrate, with a CD7 deletion in 21 of 32 biopsies examined; the CD7
      negative cells were typically the largest and most atypical forms, often in a
      cohesive array within the upper layers of the epidermis. In 17 biopsies in which
      a CD4 stain was satisfactory for evaluation, 50% or more of the intraepidermal
      population was CD4 positive in 8 biopsies, whereas in 11 biopsies 50% or more of
      the dermal infiltrate was CD4 positive. The CD4-positive cells frequently had a
      cerebriform nuclear morphology and were CD7 negative. Most cases had an admixture
      of CD8-positive lymphocytes in excess of 40% or more of the intraepidermal and/or
      dermal infiltrate; it was the dominant intraepidermal infiltrate in 10 cases. The
      CD8-positive cells, typically small, round, and CD7 positive, showed a directed
      pattern of migration into acrosyringia and suprapapillary plates, with
      satellitosis around CD4-positive/CD8-negative/CD7-negative atypical lymphocytes.
      CD56 positivity was seen among the intraepidermal lymphoid cells and roughly
      paralleled the CD8 profile. In general, CD8-positive lymphocytes dominated in
      cases of PLEVA, whereas CD4-positive lymphocytes were very conspicuous and
      composed the dominant intraepidermal populace only in those biopsies of
      progressive PL/PLC. Clonality was shown in 25 of 27 biopsies in which amplifiable
      DNA was obtained. Intraepithelial atypical lymphocytes, phenotypic abnormalities,
      and TCR-gamma rearrangements suggest that PLC and PLEVA are a form of T-cell
      dyscrasia. Lesions may follow a recalcitrant course characteristic of MF and
      premycotic disorders such as LPP. The aberrant phenotype cell is similar to that
      defining MF: a CD4-positive T lymphocyte with a CD5 and CD7 deletion. Directed
      epidermal migration seen in biopsies procured from incipient lesions along with
      occasional temporal association to viral or drug exposure suggests that an
      abnormal immune response to an antigenic trigger may be the inciting event.

PMID- 12203211
TI  - Should the diagnosis of benign prostatic hyperplasia be made on prostate needle
      biopsy?
AB  - Pathologists frequently sign out benign prostate needle biopsies as "benign
      prostatic hyperplasia (BPH)". There are no data indicating that a diagnosis of
      BPH on biopsy correlates with either gland weight or with the International
      Prostate Symptom Score (IPSS) used to measure urinary obstructive symptoms. We
      examined biopsies for average percentage of glands and average percentage of
      glands with papillary infolding per case, maximum percentage of glands and
      maximum percentage of glands with papillary infolding per core per case, and
      presence of any stromal nodules per case. BPH was measured in 2 ways: (1) IPSS
      grouped into 3 categories (mild, moderate, severe) and (2) prostate weight at
      radical prostatectomy in men with limited cancer. IPSS was classified as follows:
      mild (n = 12), moderate (n = 13), and severe (n = 10). There was no correlation
      with IPSS and any of the histologic features measured. For the 41 radical
      prostatectomy specimens, the average weight was 65.3 g (median, 56.0 g, range, 22
      to 117 g). There was no correlation between gland weight and the average or
      maximum percentage of glands, or average or maximum percentage of glands with
      papillary infolding. Stromal nodules on biopsy correlated with gland weight. In
      the 30 cases without stromal nodules on biopsy, the mean gland weight was 51.4 g.
      In the 11 cases with stromal nodules on biopsy, the mean gland weight was 77.4 g
      (P = 0.0125). However, stromal nodules were not specific for a large prostate
      (i.e., a 15 g prostate had stromal nodules on biopsy). With the exception of
      stromal nodules found on biopsy, histologic findings on biopsy are not specific
      for either clinical or pathologic BPH. Thus benign prostate biopsies should be
      signed out merely as "benign prostate tissue."

PMID- 12203212
TI  - High expression levels of insulin-like growth factor-I receptor predict poor
      survival among women with clear-cell renal cell carcinomas.
AB  - Currently, tumor stage and grade remain the only widely accepted prognostic
      indicators of clear-cell renal cell carcinoma (CC-RCC). As such, there is a need
      to identify other prognostic markers because behavior of CC-RCC cannot always be
      determined by stage alone. Recent studies of human CC-RCC cell lines suggest that
      insulin-like growth factor-I receptor (IGF-IR) may have some prognostic value for
      patients with CC-RCC. Using a population-based cohort of 48 female patients with
      CC-RCC and long-term follow-up, we tested the hypothesis that the
      immunohistochemical detection of IGF-IR expression in CC-RCC is associated with
      poorer cancer-specific survival after adjustment for stage and age at diagnosis.
      Kaplan-Meier analysis suggested that patients with CC-RCC that exhibited greater
      than 50% IGF-IR expression experienced a significantly poorer cancer-specific
      survival compared with patients with CC-RCC that exhibited less than 50% IGF-IR
      expression. The difference in survival was apparent at 2 years and remained
      throughout follow-up. Based on a Cox proportional hazard model that adjusted for
      stage and age at diagnosis, patients with tumors that exhibited greater than 50%
      IGF-IR staining were 4 times more likely to die of CC-RCC compared with patients
      whose tumors exhibited less than 50% staining (HR = 4.2; 95% confidence interval
      [CI]; 1.1-17.1). A smoothing spline with 4 degrees of freedom supported the
      results from the categorical analysis. Evidence from this population-based pilot
      investigation is consistent with laboratory data suggesting that expression of
      IGF-IR may have some prognostic implication for patients presenting with CC-RCC;
      however, confirmation in a larger study is needed.

PMID- 12203213
TI  - Expression of CD10 by stromal cells during colorectal tumor development.
AB  - CD10 is a cell surface metalloprotease expressed by a variety of normal cell
      types, including lymphoid precursor cells, germinal center B lymphocytes, and
      some epithelial cells. We noticed that stromal cells of some cancers are positive
      for CD10. In this study, we investigated the role of CD10 produced by the stromal
      cells of colorectal neoplasms in the progression of colorectal neoplasms.
      Immunohistochemical examination of CD10 and p53 was performed in 169 colorectal
      epithelial neoplasms representing various stages of carcinogenesis. The results
      were correlated with the morphologic characteristics of the neoplasms. There was
      no expression of CD10 in the stromal cells of normal colorectal tissue. CD10
      positive stromal cells were present adjacent to the tumor cells in 16 of 73
      adenomas with mild or moderate dysplasia. More frequent expression of CD10 by the
      stromal cells was detected in adenomas with severe dysplasia (12 of 17),
      intramucosal carcinomas (10 of 16), and invasive carcinomas (50 of 63) than in
      adenomas with mild or moderate dysplasia (P < 0.0001). Expression of CD10 by >
      10% of the stromal cells was detected only within the area of the invasive growth
      front of invasive carcinomas, not in adenomas and in only 1 of the intramucosal
      carcinomas. The difference between invasive and non invasive tumors was
      significant (P < 0.0001). The stromal expression of CD10 was significantly
      associated with the accumulation of p53 and a larger tumor size. These results
      indicate that CD10 expression is an integral part of colorectal carcinogenesis.
      CD10 expression seems to contribute to the invasion and thus probably facilitates
      metastasis.

PMID- 12203214
TI  - Growth index is independent of microvessel density in non-small-cell lung
      carcinomas.
AB  - Induction of angiogenesis is essential for carcinogenesis and facilitates the
      processes of tumor development and metastasis. Vascular endothelial growth factor
      (VEGF) is an important angiogenic regulator under physiologic and pathologic
      conditions. To elucidate the role of angiogenesis in malignant growth, we
      evaluated angiogenesis and VEGF expression in a panel of 68 non-small-cell lung
      carcinomas (NSCLCs) and examined their relation with the kinetic parameters,
      ploidy, and p53 protein status, which have been analyzed previously. Angiogenesis
      was estimated as microvascular density (MVD) of the tumor area by CD31
      immunodetection. Expression of VEGF was also immunohistochemically evaluated. All
      possible associations were assessed through a series of statistical methods. The
      mean MVD value was 39 microvessels/mm(2), and high VEGF immunoreactivity was
      observed in all specimens, with a mean percentage of positive cells of 73%. The
      relation between MVD and VEGF expression was not statistically significant (P =
      0.065). No association was observed between MVD or VEGF levels with the
      proliferation index, apoptotic index, tumor ploidy status, p53 expression, and
      overall survival. We conclude that in a subset of NSCLCs, angiogenesis may be
      associated with VEGF, but other factors also participate in this process.
      Angiogenesis and growth (proliferation and apoptosis) are independent and
      probably differentially operated procedures, with only growth partially
      controlled by p53 protein expression.

PMID- 12203215
TI  - Aluminum welding fume-induced pneumoconiosis.
AB  - Chronic exposure to high concentrations of fumes during aluminum arc welding
      causes a severe pneumoconiosis characterized by diffuse pulmonary accumulation of
      aluminum metal and a corresponding reduction in lung function. Aluminum fume
      induced pneumoconiosis is a rarely reported entity, of which the true incidence
      is unknown. We report the clinical, radiographic, microscopic, and microanalytic
      results of 2 coworkers, employed by the same aluminum shipbuilding facility, who
      died of complications from this disease. Scanning electron microscopy and energy
      dispersive x-ray analysis of the exogenous particle content in the lung tissue of
      these cases revealed the highest concentrations of aluminum particles (average of
      9.26 billion aluminum particles per cm(3) of lung tissue) among the 812 similar
      analyses in our pneumoconiosis database. One patient had an original clinical
      diagnosis of sarcoidosis but no evidence of granulomatous inflammation.

PMID- 12203216
TI  - Idiopathic nodular glomerulosclerosis is a distinct clinicopathologic entity
      linked to hypertension and smoking.
AB  - Idiopathic nodular glomerulosclerosis (ING) is an enigmatic condition that
      resembles nodular diabetic glomerulosclerosis but occurs in nondiabetic patients.
      We reviewed clinicopathologic features, immunohistochemical profiles, and
      outcomes in 23 patients with ING diagnosed from among 5,073 native renal biopsy
      samples (0.45%) at Columbia University from January 1996 to March 2001. This
      cohort, in which diabetes mellitus was excluded, consisted predominantly of older
      (mean age, 68.2 years) white (73.9%) men (78.3%). Clinical findings at
      presentation included renal insufficiency in 82.6% (mean serum creatinine = 2.4
      mg/dL), proteinuria (> 3 g/d in 69.6%; mean 24-hour urine protein = 4.7 g/d), and
      less frequently-full nephrotic syndrome (21.7%). There was a high prevalence of
      hypertension (95.7%; mean = 15.1 +/- 3.4 years), smoking (91.3%; mean = 52.9 +/-
      6.9 pack-years), hypercholesterolemia (90%), and extrarenal vascular disease
      (43.5%). All 23 patients had prominent diffuse and nodular mesangial sclerosis,
      glomerular basement membrane thickening, arteriosclerosis, and
      arteriolosclerosis. Immunohistochemical staining for CD34, a marker of
      endothelial cells, showed an increased number of vascular channels within ING
      glomeruli compared with normal controls. Follow-up data were available for 17
      patients, 6 of whom reached end-stage renal disease (ESRD) (35.3%). By Kaplan
      Meier estimates, the median time after biopsy to ESRD was 26 months. Predictors
      of progression to ESRD included continuation of smoking (P =.0165), lack of
      angiotensin II blockade (P =.0007), degree of tubular atrophy and interstitial
      fibrosis (P =.0517), and degree of arteriosclerosis (P =.0096). In conclusion,
      ING is a progressive vasculopathic lesion linked to hypertension and cigarette
      smoking.

PMID- 12203217
TI  - Histopathology, ultrastructure, and clinical phenotypes in thin glomerular
      basement membrane disease variants.
AB  - Recent genetic studies indicate that Alport syndrome and thin glomerular basement
      membrane disease (TMD) may both be due to COL4A3, COL4A4, and COL4A5 mutations,
      but there is continuing uncertainty concerning the diagnosis and management of
      patients without classic family history and symptoms. We examined kidney
      pathology and collagen alpha 3 to alpha 5(IV) expression in a series of 16
      patients who presented with overlapping signs between TMD and Alport nephritis.
      All patients presented with hematuria, and 11 also had proteinuria, of whom 5 had
      nephrotic range proteinuria. Only 9 had family history of hematuria. In 9 of 16
      (60%) we found premature glomerulosclerosis in the renal biopsies. Three of 16
      had predominantly wide, lamellated glomerullar basement membranes (GBM), and in
      these, alpha 3 to alpha 5(IV) was absent in glomeruli or skin, diagnostic of
      Alport nephritis. One patient (12) had a very wide GBM with intramembranous
      lucencies but no lamellation. Skin biopsy was collagen alpha 5(IV) positive. Nine
      of 16 patients had predominantly thin GBM by electron microscopy, and 3 had thin
      and slightly lamellated GBM. Collagen alpha 3 to alpha 5(IV) expression in the
      kidney or skin biopsy was present in all of the latter 12 patients. Three
      patients had end-stage renal disease, 7 patients had hypertension, and 1 patient
      had chronic renal failure. We found that of the 16 patients with presumed TMD, 3
      had X-linked Alport nephritis, 2 appeared to have autosomal recessive Alport
      nephritis, and the remaining patients had either an Alport or a TMD variant. The
      latter had histologic and/or clinical evidence of progressive renal disease,
      including premature glomerulosclerosis, hypertension, sustained proteinuria, and
      either thin or slight GBM lamellation focally, and preserved alpha 3 to alpha
      5(IV) expression. These patients have a TMD variant, but an Alport variant with a
      potentially transmissible severe defect different from benign hematuria cannot be
      excluded.

PMID- 12203219
TI  - Atypical blasts and bone marrow necrosis associated with near-triploid relapse of
      acute promyelocytic leukemia after arsenic trioxide treatment.
AB  - The pathologic features of acute promyelocytic leukemia (APL) with
      t(15;17)(q22;q21) are highly characteristic, which with few exceptions enable a
      firm diagnosis to be made on morphologic grounds. An APL patient in first relapse
      presented with large, bizarre circulating blasts and bone marrow necrosis 2 weeks
      after chemotherapy consolidation for an arsenic trioxide-induced remission.
      Although a morphologic diagnosis could not be reached, cytogenetic investigations
      showed a near-triploid clone with t(15;17), confirming APL in second relapse.
      This case showed that clonal evolution with additional karyotypic aberrations
      might alter the blast morphology and pathologic features in APL.

PMID- 12203218
TI  - Human herpesvirus-8-associated lymphoma of the bowel in human immunodeficiency
      virus-positive patients without history of primary effusion lymphoma.
AB  - This report describes two cases of human herpesvirus-8 (HHV-8)-associated large
      cell lymphoma of the bowel in human immunodeficiency virus (HIV)-positive men.
      Immunohistochemistry provides evidence of HHV-8 infection of the lymphoma cells
      (LNA1+, vIL-6+). In both cases, lymphoma cells were coinfected by the Epstein
      Barr virus. One case was of B-cell lineage, but the second one was of null
      phenotype with isolated expression of the CD3 molecule. However, in the latter
      case, assessment of B- or T-cell clonality remained elusive. The chief finding
      for these two cases was the lack of history of primary effusion lymphoma. There
      was an apparent restriction of the tumor to the large bowel in the first case.
      For the second case, the bowel tumor was preceded by lymph node and liver
      involvement. The cases suggest that the incidence of HHV-8 infection in large
      cell lymphoma arising in the setting of HIV infection (other than primary
      effusion lymphoma) may be underestimated and that the detection of the viral gene
      products would be appropriate for greater understanding of the pathogenesis of
      these tumors. HUM PATHOL 33:846-849.

PMID- 12203220
TI  - Two case reports of childhood liver cell adenomas harboring beta-catenin
      abnormalities.
AB  - The benign epithelial neoplasm liver cell adenoma is rare, especially in
      childhood. We report 2 such cases, 1 of which was associated with Prader-Willi
      syndrome. Differential diagnosis of the liver cell adenomas on the basis of
      histopathologic findings proved difficult and was based on the absence of
      cellular and nuclear atypia, mitotic activity, and invasive growth. In both
      cases, immunohistochemical staining demonstrated the nuclear accumulation of beta
      catenin, and in 1 case, the tumor cells carried a mutation of the beta-catenin
      gene. Recently, disregulation of the Wnt/beta-catenin pathway, attributable to
      abnormalities of the beta-catenin gene, has been reported to be a major event in
      the development of hepatocellular carcinomas and hepatoblastomas. Our report may
      be the first to describe the beta-catenin abnormalities in childhood liver cell
      adenoma. These findings imply that abnormalities of beta-catenin can be an early
      initiating event in human liver tumorigenesis.

PMID- 12203221
TI  - Endometrioid carcinoma of the endometrium with an invasive component of minimal
      deviation carcinoma.
AB  - Minimal deviation endometrioid adenocarcinoma is a rare pathological variant of
      endometrioid adenocarcinoma. We describe a case representing another rare variant
      of endometrioid adenocarcinoma composed of both typical and minimal deviation
      endometrioid adenocarcinoma in a 45-year-old woman. Macroscopically, the cervix
      was of normal size but it had an indurated consistency. The myometrium was
      unremarkable. Microscopically, in addition to the typical endometrioid
      adenocarcinoma that involved 75% of the endometrium, there was a proliferation of
      mildly atypical endometrial type glands sparsely distributed in the fibrovascular
      tissue, typical of minimal deviation endometrioid adenocarcinoma. The latter
      component extended downward from the endomyometrial junction and involved focal
      areas of the uterine body and isthmus, diffusely invaded the entire cervix and
      focally the cervical resection margins. Focal transitional areas between typical
      and minimal deviation endometrioid adenocarcinoma were identified. Due to a
      relatively normal gross appearance and the microscopic deceptively benign looking
      appearance, minimal deviation endometrioid adenocarcinoma may pose problems of
      obtaining adequate sampling and evaluating the thickness of invasion of the
      endometrial carcinoma on gross, as well as microscopic, examination. HUM PATHOL
      33:856-858.

PMID- 12203222
TI  - Application of (13)C-filtered (1)H NMR to evaluate drug action on gluconeogenesis
      and glycogenolysis simultaneously in isolated rat hepatocytes.
AB  - The effects of two inhibitors of hepatic glucose production, AICAR (5
      aminoimidazole-4-carboxamide riboside) and metformin, whose precise mechanisms of
      action are a matter of some controversy, have been investigated in isolated rat
      hepatocytes by application of a novel NMR-based method whereby effects on
      metabolic flow from the two glucose-producing pathways, glycogenolysis and
      gluconeogenesis, and also lactate production, can be studied simultaneously.
      Hepatocytes were pre-incubated for 24 h with 15 mM 1-(13)C-glucose to load the
      cells with labeled glycogen, which under subsequent glycogenolytic conditions
      would yield predominantly 1-(13)C glucose and 3-(13)C-lactate, followed (after
      washing) by incubation in media with 2-(13)C-glycerol, which under subsequent
      gluconeogenic conditions would yield 2,5-(13)C-glucose, or if metabolized to
      lactate, 2-(13)C-lactate. Glucose production was then stimulated by glucagon for
      3 h in the absence or presence of the inhibitors and then incubation media were
      analyzed by (13)C-HSQC (heteronuclear single quantum coherence)-filtered (1)H NMR
      spectra. The results show that metformin only inhibits glucose production by
      inhibition of gluconeogenesis, but also that it increases lactate production from
      both glycogenolysis and from glycerol, whereas, and contrary to expectations,
      AICAR inhibits glucose production by inhibiting both gluconeogenesis and
      glycogenolysis, and also increases lactate production from glycerol. The data
      show that application of this methodology can be used to answer important
      questions about drug action on hepatic metabolism that are not readily accessible
      by alternative means.

PMID- 12203223
TI  - Differentiation of hydatid cyst from cysticercus cyst by proton MR spectroscopy.
AB  - The metabolite patterns obtained by ex vivo proton MR spectroscopy of fluid from
      different locations of hydatid cysts of sheep and humans (n = 16) and cysticercus
      cysts of swine and humans (n = 25) were compared with an objective of
      differentiating the two parasites on the basis of their metabolite pattern. The
      spectra from hydatid fluid differed from cysticercus cyst by the absence of
      creatine in the former. When the hydatid cyst was fertile, malate and/or fumarate
      was also observed, which was absent in cysticercus cyst. The most likely
      explanation for the presence of creatine only in the cysticercus fluid is its
      active diffusion from the surrounding host tissue along with a contribution from
      the musculature present in the bladder wall of the cyst.

PMID- 12203224
TI  - High-resolution magic angle spinning MRS of breast cancer tissue.
AB  - High-resolution magic angle spinning (HR MAS) may develop into a new diagnostic
      tool for studying intact tissue samples, and several types of cancer have been
      investigated with promising results. In this study HR MAS spectra of breast
      cancer tissue from 10 patients have been compared to conventional high-resolution
      spectra of perchloric acid extracts of the same tissue type. The HR MAS spectra
      show resolution comparable to spectra of extracts, and two-dimensional techniques
      lead to identification of a majority of the constituents. More than 30 different
      metabolites have been detected and assigned. To our knowledge this is the most
      detailed assignment of biochemical components in intact human breast tissue. The
      spectra of intact breast cancer tissue differ from perchloric acid extracts by
      the presence of lipids and fewer signals in the low field region. HR MAS analysis
      of intact breast tissue specimens is a rapid method, providing spectra with
      resolution where relative quantification of the majority of the detected
      metabolites is possible.

PMID- 12203225
TI  - In vivo brain (31)P-MRS: measuring the phospholipid resonances at 4 Tesla from
      small voxels.
AB  - An optimized phosphorous ((31)P) three-dimensional chemical-shift imaging (3D
      CSI) protocol was developed at 4 T to study the phospholipid metabolism from
      discrete regions in the human brain without the need for (1)H-decoupling or
      nuclear Overhauser enhancement (NOE). In this study, a spherically bound,
      weighted average, random point omission 3D-CSI technique was developed and
      tested, based on methods proposed in the literature. The technique yields a
      significant (p < 0.001, two-tailed, 5% confidence level) increase in signal-to
      noise (SNR) efficiency over conventional 3D-CSI (phantom 32%), without an
      increase in voxel bleedthrough. An automated time-domain fitting procedure
      utilizing prior spectral knowledge quantified the individual brain phospholipid
      metabolites from 15 cm(3) effective (8.0 cm(3) nominal) volumes from the
      left/right-parieto-occipital cortex and left/right thalamus in 10 normal
      volunteers. Individual constituents from the phosphomonoester (PME) region;
      phosphoethanolamine (PEth), phosphocholine (PCh) and the phosphodiester (PDE)
      region; glycerophosphoethanolamine (GPEth), glycerophosphocholine (GPCh) and
      membrane phospholipids (MP) were separately quantified to assess the precision of
      our method at 4 T against previous (1)H-decoupled (31)P-MRS brain studies at
      lower fields and much larger voxels. Derived concentrations (mM/l tissue) for
      PEth, PCh, GPEth, GPCh and MP in the left-parieto-occipital cortex were 0.81 +/-
      0.21, 0.46 +/- 0.14, 0.74 +/- 0.30, 1.15 +/- 0.43 and 1.54 +/- 0.95 mM,
      respectively, and 0.94 +/- 0.16, 0.46 +/- 0.17, 0.83 +/- 0.22, 1.14 +/- 0.40 and
      1.26 +/- 0.78 mM for the right parieto-occipital cortex. Derived concentrations
      (mM/l tissue) for PEth, PCh, GPEth, GPCh and MP in the left-thalamus were 0.69 +/
      0.18, 0.42 +/- 0.16, 0.63 +/- 0.20, 1.05 +/- 0.42 and 0.93 +/- 0.56 mM,
      respectively, and 0.68 +/- 0.24, 0.34 +/- 0.18, 0.60 +/- 0.23, 1.09 +/- 0.36 and
      0.74 +/- 0.48 mM for the right-thalamus. This is the first study to our knowledge
      that has been able to quantify each of these individual phospholipid metabolites
      from such small voxels in the brain within a clinically reasonable scan time and
      without (1)H-decoupling or NOE.

PMID- 12203226
TI  - The effects of drugs modulating K(+) transport on Rb(+) uptake and distribution
      in pig hearts following regional ischemia: (87)Rb MRI study.
AB  - The effects of drugs that can modulate passive permeability of K(+) into
      cardiomyocytes in normal and reperfusion-damaged cardiac muscle were assessed.
      Rubidium ion (Rb(+)) was used as a K(+) tracer and (87)Rb-MRI as a detection
      method. The left anterior descending artery (LAD) of isolated pig hearts perfused
      with Krebs-Henseleit buffer (KHB) was occluded for 2 h and subsequently
      reperfused for 2 h with KHB containing 4.7 mM RbCl instead of KCl. The buffer
      contained either a blocker of ATP-sensitive K(+) channels (K(ATP)), glibenclamide
      (Glib, 3 micro M), a K(ATP) opener, pinacidil (Pin, 10 micro M), a
      K(+)/Na(+)/2Cl(-) co-transporter inhibitor, bumetanide (Bum, 10 micro M) or no
      drug (control). Upon reperfusion three-dimensional (87)Rb MR images were acquired
      to obtain kinetics of Rb(+) uptake and its distribution. Areas at risk (AAR) and
      areas of necrosis were determined by Evans Blue and triphenyl tetrazolium
      chloride staining, respectively. Rb(+) uptake kinetics in the remote posterior
      (Pos) wall were similar in all groups. The kinetics remained monoexponential in
      the affected anterior (Ant) wall and the uptake rates were 32, 36, 37 and 21% of
      that in the Pos wall in the control, Glib, Pin and Bum groups, respectively.
      Infarct sizes determined histologically as a percentage of total ventricular
      (left + right) mass (14-22%) corresponded to sizes of areas with 20-40% of
      maximal Rb image intensity [I(Rb)(max), 15-22%], except for the Pin group (12.5
      vs 21%). The sizes of areas with 20-50% of I(Rb)(max) (30-36%) closely correlated
      with those of AAR determined histologically (31-33%). Lactate dehydrogenase
      release did not differ in all groups. We conclude that: (1) reperfusion damage
      quickly inhibits Rb(+) uptake; (2) Rb(+) uptake in normal and reperfused tissue
      does not significantly depend on K(ATP) or the K(+)/Na(+)/2Cl(-) cotransporter;
      (3) areas with 20-40% of maximal image intensity correspond to infarct areas.

PMID- 12203227
TI  - Changes in phosphate metabolism in thymoma cells suggest mechanisms for
      resistance to dexamethasone-induced apoptosis. A 31P NMR spectroscopic study of
      cell extracts.
AB  - Treatment of the mouse thymoma-derived WEHI7.2 cell line with dexamethasone, a
      synthetic glucocorticoid, causes the cells to undergo apoptosis. Previous studies
      have shown that WEHI7.2 cell variants with an increased antioxidant defense
      exhibit increased resistance to dexamethasone-induced apoptosis, suggesting that
      oxidative stress may play a role in glucocorticoid-induced apoptosis. In this
      work we compared metabolic profiles of WEHI7.2 parental cells with those of
      WEHI7.2 variants with an increased antioxidant defense or overexpressing bcl-2,
      to determine whether bolstering the antioxidant defense results in altered
      metabolic parameters that could translate into increased resistance to
      dexamethasone-induced apoptosis. WEHI7.2 parental cells and cells overexpressing
      catalase, thioredoxin or bcl-2, or selected for resistance to 200 micro M
      H(2)O(2) were cultured in low-glucose DMEM medium supplemented with 10% calf
      serum, and extracted using chloroform-methanol-water (1:1:1). Metabolites
      contained in the aqueous and organic phases of the extracts were processed
      separately and subjected to high-resolution (31)P NMR spectroscopy. In most of
      the steroid-resistant variants, ATP levels and energetic status were decreased
      compared with the steroid-sensitive parental cell line, while the concentrations
      of hexose and triose phosphates were increased. Furthermore, the ratio of choline
      containing phospholipids to ethanolamine-containing phospholipids was generally
      reduced in steroid-resistant cells. Phosphatidylethanolamine and its derivatives
      contain a higher amount of polyunsaturated fatty acids (PUFA) than the choline
      containing analogs, and PUFA are readily oxidized by reactive oxygen species.
      Therefore, an increased initial amount of phosphatidylethanolamine may increase
      the 'buffering capacity' of this antioxidant and may thus contribute to the
      steroid resistance of WEHI7.2 variants.

PMID- 12203229
TI  - Identification of the main by-products of the developing agent N-hydroxyethyl-N
      ethyl-3-methyl-p-phenylenediamine in photographic effluents by liquid
      chromatography/mass spectrometry.
AB  - N-Hydroxyethyl-N-ethyl-3-methyl-p-phenylenediamine (CD(4)) is commonly used as a
      developing agent in color photographic processes. The main by-products formed in
      developer baths used in the process were separated and identified by liquid
      chromatography/electron ionization mass spectrometry (LC/EI-MS) and liquid
      chromatography/atmospheric pressure ionization mass spectrometry (LC/API-MS). A
      number of side reactions, in addition to the main reactions involved in the
      developing process, were found to occur. Such side reactions involved in the
      formation of CD(4) by-products included oxidation, hydroxylation, sulfonation and
      the formation of coupling products. A reaction pathway for the degradation of
      CD(4) based on the nature of the by-products identified is proposed and
      discussed.

PMID- 12203228
TI  - Ultrafast liquid chromatography/tandem mass spectrometry bioanalysis of polar
      analytes using packed silica columns.
AB  - Ultrafast liquid chromatography/tandem mass spectrometry (LC/MS/MS) bioanalysis
      was demonstrated with the use of packed silica columns operated under elevated
      flow rates. A special effort has been made to achieve ultrafast analysis without
      sacrificing chromatographic resolution. Two multiple analyte/metabolites assays,
      (1) morphine/morphine-6-glucuronide(M6G)/morphine-3-glucuronide(M3G) and (2)
      midazolam/1'-hydroxymidazolam/4-hydroxymidazolam, were used to demonstrate the
      speed, sensitivity, peak shape and separation of the ultrafast methods utilizing
      silica columns. In both methods adequate chromatographic separation was a
      necessity because quantitation results would be otherwise compromised due to
      cross interference between different selected reaction monitoring (SRM)
      transitions. Baseline resolutions between morphine, M6G and M3G in human plasma
      extracts were achieved within 30 s on a 50 x 3 mm Betasil silica column operated
      at 4 mL/min of isocratic acetonitrile/water mobile phase. The total injection-to
      injection cycle time was 48 s with a simple, single-autosampler/single-column
      setup, when a Shimadzu SIL-HT autosampler was used. Baseline resolution between
      1'-hydroxymidazolam and 4-hydroxymidalolam in monkey plasma extracts was achieved
      within 33 s using similar conditions. Due to the absence of carry-over in this
      case, no rinsing of the injection needle was necessary, resulting in a cycle time
      of only 39 s/sample. These ultrafast methods were successfully used to analyze
      extracted biological samples and proved to be reproducible, reliable and
      generated equivalent pharmaco-kinetic (PK) results to those obtained by regular
      flow LC/MS/MS analysis to support discovery PK studies.

PMID- 12203230
TI  - A combined ion source for fast switching between electrospray and matrix-assisted
      laser desorption/ionization in Fourier transform ion cyclotron resonance mass
      spectrometry.
AB  - A new ion source has been developed for Fourier transform ion cyclotron resonance
      mass spectrometry (FTICRMS) that enables quick changes between matrix-assisted
      laser desorption/ionization (MALDI) and electrospray ionization (ESI) modes. When
      operating as an ESI source, the sample solution is sprayed through an angled
      nebulizer. The generated ions pass through a glass capillary followed by a
      skimmer and three sequential hexapole ion guides. Ions can be accumulated in the
      third hexapole (storage hexapole) before they are injected into the ICR trap. The
      second hexapole is mounted on a movable platform which also carries the MALDI
      sample plate. During the switch from ESI to MALDI, this platform moves the second
      hexapole out of the hexapole series and locates a MALDI sample plate with 384
      sample positions into the area directly in front of the storage hexapole. The
      storage hexapole is in a medium pressure chamber (MPC) which has windows both for
      the incoming laser beam and for the observation optics, as well as a gas tube for
      pulsing collision gas into the chamber. During the MALDI operation the focused
      laser beam enters the MPC, passes between the hexapole rods and irradiates a
      MALDI sample on the target plate. The sample molecules are desorbed/ionized into
      the storage hexapole and simultaneously cooled by collisions with the pulsed gas.
      Ions desorbed from multiple laser shots can be accumulated in this hexapole
      before they are transferred to the ICR trap. With the combined ion source a
      computer-controlled switch between MALDI and ESI modes is possible in less than a
      minute, depending on the position of the MALDI target on the 384-spot plate.
      Immediate acquisition of mass spectra is possible after mode switching without
      the need for tuning or re-calibration.

PMID- 12203231
TI  - Quantification of clenbuterol in equine plasma, urine and tissue by liquid
      chromatography coupled on-line with quadrupole time-of-flight mass spectrometry.
AB  - Clenbuterol (CBL) is a potent beta(2)-adrenoceptor agonist used for the
      management of respiratory disorders in the horse. The detection and
      quantification of CBL can pose a problem due to its potency, the relatively low
      dose administered to the horse, its slow clearance and low plasma concentrations.
      Thus, a sensitive method for the quantification and confirmation of CBL in
      racehorses is required to study its distribution and elimination. A sensitive and
      fast method was developed for quantification and confirmation of the presence of
      CBL in equine plasma, urine and tissue samples. The method involved liquid-liquid
      extraction (LLE), separation by liquid chromatography (LC) on a short cyano
      column, and pseudo multiple reaction monitoring (pseudo-MRM) by electrospray
      ionization quadrupole time-of-flight tandem mass spectrometry (ESI-QTOF-MS/MS).
      At very low concentrations (picograms of CBL/mL), LLE produced better extraction
      efficiency and calibration curves than solid-phase extraction (SPE). The
      operating parameters for electrospray QTOF and yield of the product ion in MRM
      were optimized to enhance sensitivity for the detection and quantification of
      CBL. The quantification range of the method was 0.013-10 ng of CBL/mL plasma,
      0.05-20 ng/0.1 mL of urine, and 0.025-10 ng/g tissue. The detection limit of the
      method was 13 pg/mL of plasma, 50 pg/0.1 mL of urine, and 25 pg/g of tissue. The
      method was successfully applied to the analysis of CBL in plasma, urine and
      various tissue samples, and in pharmacokinetic (PK) studies of CBL in the horse.
      CBL was quantified for 96 h in plasma and 288 h in urine post-administration of
      CLB (1.6 micro g/kg, 2 x daily x 7 days). This method is useful for the detection
      and quantification of very low concentrations of CBL in urine, plasma and tissue
      samples.

PMID- 12203232
TI  - Spiking structure of amplitude characteristics for ion trajectories in
      hyperboloidal mass spectrometers: the theory.
AB  - We present a theory that describes a 'spiking' structure of the amplitude
      characteristics for trajectories of ions within a hyperboloidal mass spectrometer
      (HMS) discovered and reported recently. This effect, as well as modulation
      parametric resonance, relates directly to a fine structure of the stability
      diagram for a HMS. A method of extremum characteristic solutions of the Hill
      equation (developed in our laboratory earlier) has been used in this work. Simple
      expressions determined the shape of narrow dips (or reversed peaks) in the
      amplitude of ion oscillation versus stability parameter curves and conditions of
      their appearance are presented. The results that were calculated from analytical
      expressions are compared with those obtained from direct computations of ion
      trajectories in a HMS. This effect with respect to a nature of 'black holes' or
      'black canyons' observed earlier in investigations of trapping efficiency and ion
      trapping within ion traps is discussed.

PMID- 12203233
TI  - Some properties of ion trajectories in the radial plane of an axially symmetric
      ion trap.
AB  - In this article we analyse the trajectories of externally generated ions injected
      in the radial plane into the ion trap. The shape of the envelope curves for two
      dimensional (2D) ion trajectories is determined. Conditions under which these
      envelope curves can be transformed into circles are found. We show that the
      amplitude of ion oscillations is a minimum in this case and that this mode
      corresponds to optimised ion trapping conditions. Also we discuss a ring-shaped
      ion trap mass spectrometer electrode system which consists of two ring
      electrodes, and which utilises ion trajectories with circular envelope curves.

PMID- 12203234
TI  - Study of structural characteristic features of phenanthriondolizidine alkaloids
      by fast atom bombardment with tandem mass spectrometry.
AB  - The mass spectrometric behavior of phenanthroindolizidine alkaloids has been
      investigated in detail by positive ion fast atom bombardment tandem mass
      spectrometry (FAB-MS/MS) combined with collision-induced dissociation (CID). The
      fragmentation has been correlated with the skeleton structure and positions of
      substituents. The product ions arising from retro-Diels-Alder cleavages differ
      clearly for compounds with different skeletons. The substituents at C-14 were
      observed to markedly influence the fragmentation pathway of [M + H](+) ions. A
      diversity of dissociation behavior initiated by the variation of substituents on
      the aromatic ring was also observed in the CID spectra. Product ions resulting
      from loss of CH(4) were obtained for compounds in which both C-6 and C-7 are
      occupied by methoxy groups. FAB-MS/MS spectra can reflect the connection between
      the fragmentation behavior and structural features of these
      phenanthroindolizidine alkaloids rapidly and effectively, and should prove to be
      a powerful method to determine the structures of related compounds.

PMID- 12203235
TI  - Amino acid and peptide conjugates of protoporphyrin: preparation and analysis by
      high-performance liquid chromatography, high-performance liquid
      chromatography/electrospray ionization mass spectrometry and matrix-assisted
      laser desorption/ionization time-of-flight mass spectrometry.
AB  - Amino acid and peptide conjugates of protoporphyrin have been prepared by
      reacting protoporphyringen with cysteine, glutathione and peptides containing a
      free thiol group under acidic conditions. The conjugates were formed by the
      addition of the thioamino acids or peptides to the vinyl groups of protoporphyrin
      during the autoxidation of protoporphyinogen to protoporphyrin and is free
      radical-mediated. The conjugates were separated by high-performance liquid
      chromatography (HPLC) and characterized by HPLC/electrospray ionization mass
      spectrometry (HPLC/ESI-MS) and matrix-assisted laser desorption/ionization time
      of-flight mass spectrometry (MALDI-TOFMS). All the conjugates formed were
      diconjugates consisting of diastereoisomers.

PMID- 12203236
TI  - Mass spectrometric studies of benzoxazine resorcarenes.
AB  - Eleven differently substituted 3,4-dihydro-2H-1,3-benzoxazine resorcarenes were
      studied by electrospray ionisation (ESI) and matrix-assisted laser
      desorption/ionisation (MALDI) mass spectrometry, using Fourier transform ion
      cyclotron resonance (FT-ICR) and time-of-flight (TOF) mass spectrometers,
      respectively. Under ESI conditions it was possible to transfer the intact
      resorcarenes from solution to the gas phase, yielding [M + H](+) and [M + 2H](+)
      ions as the main ions observed. Energy increase of the ions induced ready
      decomposition through successive eliminations of four CH(2)NR groups. Ion
      molecule reactions showed that the ionising proton was situated somewhere inside
      the molecule and could not be reached with neutral reagent gases. In the host
      guest complexation experiments, the benzoxazine resorcarenes studied turned out
      to be poor hosts for alkali metal and ammonium ions. In MALDI experiments, 2,5
      dihydroxybenzoic acid proved to be the best matrix for these compounds. However,
      the intensity of the [M + H](+) ions was low for all compounds, and extensive
      fragmentation with consecutive elimination of CH(2)NR groups was observed.

PMID- 12203237
TI  - Analysis of peptides using partial (no discharge) atmospheric pressure chemical
      ionization conditions with ion trap mass spectrometry.
AB  - A novel approach, based on the use of atmospheric pressure chemical ionization
      ion trap mass spectrometry (APCI-ITMS) conditions, but without using corona
      discharge, was used to analyze peptides. The proposed method was applied to three
      standard peptides (bombesin, trityrosine and tyrosine-glycine-glycine) as well as
      peptides obtained through enzymatic digestion of two standard proteins (horse
      cytochrome c and horse myoglobin).

PMID- 12203238
TI  - Quantitative analysis of two-dimensional gel-separated proteins using
      isotopically marked alkylating agents and matrix-assisted laser
      desorption/ionization mass spectrometry.
AB  - We describe a simple approach for the relative quantification of individual
      proteins within a mixture. The method is based on the differential labelling of
      the mixtures by use of a commercially available acrylamide and deuterium-labelled
      [2,3,3'-d(3)]-acrylamide to alkylate proteins prior to two-dimensional (2-D) gel
      electrophoresis. The tryptic digests of the separated proteins were subjected to
      reflector matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF)
      analysis and the relative peak heights of cysteine-containing peptides were used
      to quantify their precursor proteins. This approach was tested for the relative
      quantification of proteins within an artificial mixture of standard proteins and
      for proteins observed in a 2-D map of rat serum. A good correlation was found
      between the measured ratios derived from MALDI-TOF data and those theoretically
      calculated prior to 2-D analysis via known mixing ratios of the two alkylating
      reagents. The described procedure has proved to be effective for comparative
      measurements of protein abundances within the investigated mixtures.

PMID- 12203239
TI  - Towards understanding some ion intensity relationships for the tandem mass
      spectra of protonated peptides.

PMID- 12203240
TI  - Rapid quantitation of globotriaosylceramide in human plasma and urine: a
      potential application for monitoring enzyme replacement therapy in Anderson-Fabry
      disease.
AB  - A method for measuring globotriaosylceramide (Gb3, or GL3) levels in plasma and
      urine of humans affected by Anderson-Fabry disease has been developed. The
      analyses are performed using flow injection analysis-electrospray ionization
      tandem mass spectrometry (FIA-ESI-MS/MS). The method is rapid, sensitive and
      hence suitable for high-throughput analyses, requiring only a simple 50-fold
      dilution for the preparation of plasma and urine samples. The detection of the
      analytes of interest was achieved using a triple quadrupole instrument operating
      in the multiple reaction monitoring mode. The linearity of the calibration
      standard responses, the intra- and inter-assay precision, the accuracy and the
      detection limit of the method were evaluated. The proposed method allows a rapid
      and accurate assessment of globotriaosylceramide in biological samples. Data
      obtained from healthy volunteers and Anderson-Fabry affected subjects suggest a
      potential role for this technique in monitoring the effectiveness of Anderson
      Fabry disease therapy. The results obtained in two actual cases treated with
      enzyme replacement therapy are reported and discussed.

PMID- 12203242
TI  - Identification of 1-hydroxypyrene glucuronide in tissue of marine polychaete
      Nereis diversicolor by liquid chromatography/ion trap multiple mass spectrometry.
AB  - 1-Hydroxypyrene glucuronide is identified as the single major aqueous metabolite
      of the tetracyclic aromatic hydrocarbon pyrene, in tissue from a deposit-feeding
      marine polychaete, Nereis diversicolor. Identification was performed using an ion
      trap mass spectrometer fitted with an atmospheric pressure chemical ionization
      (APCI) probe and connected to a high-performance liquid chromatography/diode
      array detector (HPLC/DAD) system. Besides 1-hydroxypyrene, the 339-nm UV trace of
      tissue samples from pyrene-exposed worms showed only one dominant peak that could
      be related to pyrene metabolism. Negative APCI-MS of this supposed 1-
      hydroxypyrene conjugate gave a characteristic signal at m/z 429 corresponding to
      the molecular ion of 1-hydroxypyrene glucuronide plus eluent adducts ([M - H +
      2H(2)O](-)). Fragmentation pathways were studied by isolating the abundant ion at
      m/z 429 in the ion trap and performing multiple mass spectrometric experiments
      (MS(n)). The fragmentations observed were consistent with the proposed
      identification. Two low intensity LC peaks that could be related to pyrene
      metabolism by their DAD absorption spectra were also present in the 339-nm UV
      chromatogram of tissue samples. However, these peaks could not be identified by
      their mass spectra in negative ion mode due to ion suppression by very abundant
      co-eluting impurities. The present method shows that LC/MS(n) is a fast and
      useful analytical tool for identification of aqueous polycyclic aromatic
      hydrocarbon biotransformation products in samples from relatively small marine
      invertebrates with limited sample preparation.

PMID- 12203245
TI  - A strategy for a post-method-validation use of incurred biological samples for
      establishing the acceptability of a liquid chromatography/tandem mass
      spectrometric method for quantitation of drugs in biological samples.
AB  - Validated liquid chromatography/tandem mass spectrometric (LC/MS/MS) methods are
      now widely used for quantitation of drugs in post-dose (incurred) biological
      samples for the assessment of pharmacokinetic parameters, bioavailability and
      bioequivalence. In accordance with the practice currently accepted within the
      pharmaceutical industry and the regulatory bodies, validation of a bioanalytical
      LC/MS/MS method is performed using standards and quality control (QC) samples
      prepared by spiking the drug (the analyte) into the appropriate blank biological
      matrix (e.g. human plasma). The method is then declared to be adequately
      validated for analyzing incurred biological samples. However, unlike QC samples,
      incurred samples may contain an epimer or another type of isomer of the drug,
      such as a Z or E isomer. Such a metabolite will obviously interfere with the
      selected reaction monitoring (SRM) transition used for the quantitation of the
      drug. The incurred sample may also contain a non-isomeric metabolite having a
      molecular mass different from that of the drug (such an acylglucuronide
      metabolite) that can still contribute to (and hence interfere with) the SRM
      transition used for the quantitation of the drug. The potential for the SRM
      interference increases with the use of LC/MS/MS bioanalytical methods with very
      short run times (e.g. 0.5 min). In addition, a metabolite can potentially undergo
      degradation or conversion to revert back to the drug during the multiple steps of
      sample preparation that precede the introduction of the processed sample into the
      LC/MS/MS system. In this paper, we recommend a set of procedures to undertake
      with incurred samples, as soon as such samples are available, in order to
      establish the validity of an LC/MS/MS method for analyzing real-life samples.
      First, it is recommended that the stability of incurred samples be investigated
      'as is' and after sample preparation. Second, it is recommended that potential
      SRM interference be investigated by analyzing the incurred samples using the same
      LC/MS/MS method but with the additional incorporation of the SRM transitions
      attributable to putative metabolites (multi-SRM method). The metabolites
      monitored will depend on the expected metabolic products of the drug, which are
      predictable based on the functional groups present in the chemical structure of
      the drug. Third, it is recommended that potential SRM interference be further
      investigated by analyzing the incurred samples using the multi-SRM LC/MS/MS
      method following the modification of chromatographic conditions to enhance
      chromatographic separation of the drug from any putative metabolites. We will
      demonstrate the application of the proposed strategy by using a carboxylic acid
      containing drug candidate and its acylglucuronide as a putative metabolite.
      Plasma samples from the first-in-man (FIM) study of the drug candidate were used
      as the incurred samples.

PMID- 12203246
TI  - High-throughput logP measurement using parallel liquid
      chromatography/ultraviolet/mass spectrometry and sample-pooling.
AB  - A novel approach to high-throughput logP measurement based on liquid
      chromatography/ultraviolet/mass spectrometry (LC/UV/MS) is proposed. The logP
      value is determined by correlation with the logk value, where k is the capacity
      factor k = (t(r)-t(0))/t(0), with the logP value using a defined set of
      standards. Since the analyte retention time (t(r)) is determined from the
      appropriate extracted ion chromatogram (EIC), there are no interferences from
      impurities and this allows the pooling of multiple compounds into one injection.
      To ensure the accuracy and instrument robustness in a routine high-throughput
      environment, a simple and MS-friendly mobile phase consisting of 20 mM ammonium
      carbonate (pH 8.0) for basic compounds or 20 mM ammonium formate (pH 1.0) for
      acidic compounds, both in combination with methanol at a ratio of 45:55, is used.
      This approach has been successfully used on single as well as parallel multi
      channel LC/UV/MS systems to screen small to large sets of lead compounds and
      their analogs. A high-throughput capability to analyze over 1000 compounds per
      day has been achieved.

PMID- 12203248
TI  - Effects of nebulizing and drying gas flow on capillary electrophoresis/mass
      spectrometry.
AB  - This study was focused on examining the influence of gas flow parameters on
      capillary electrophoresis/mass spectrometry (CE /MS) performance using sheath
      liquid CE /MS interfaces. The effects of nebulizing and drying gas velocity and
      drying gas temperature on CE separation and MS detection sensitivity were
      systematically determined. Nebulizing gas velocity was observed to be a critical
      parameter in the optimization of CE /MS method, since it affected both MS
      detection sensitivity, and also CE separation efficiency for one interface design
      tested. Better detection sensitivity was obtained when the nebulizing gas
      velocity was increased. However, high velocity of the nebulizing gas flow can
      cause a hydrodynamic bulk flow inside the CE capillary, thus clearly increasing
      the apparent mobility and decreasing the resolution obtained for the compounds
      studied. Increasing the drying gas velocity or temperature did not affect the
      apparent mobility or the separation efficiency and the temperature could be
      increased to achieve the optimal detection sensitivity in the CE /MS analysis.
      For comparison, the effects of nebulizing gas flow were studied using a different
      design of the coaxial sheath-liquid CE /MS interface, and in this case better
      detection sensitivity but no effect on CE separation efficiency was observed with
      increased nebulizing gas velocity. These different effects of nebulizing gas flow
      on the CE bulk flow were concluded to result from pressure differences at the tip
      of the CE capillaries for the different CE /MS interface arrangements. It is
      therefore recommended that the cross-sectional dimensions of the fused-silica and
      steel capillaries, and the gas streamlines, should be optimized when CE /MS
      interfaces are built. Moreover, the effect of gas flow on CE separation should be
      studied when optimizing the CE /MS operation parameters.

PMID- 12203249
TI  - Studying protein-carbohydrate interactions by amide hydrogen/deuterium exchange
      mass spectrometry.
AB  - Protein-carbohydrate interactions play a significant role in biological
      processes. Presented here is the novel application of amide hydrogen/deuterium
      exchange mass spectrometry (amide exchange-MS) to the study of the interaction
      between a protein and its carbohydrate substrate. The degree of deuterium
      incorporation into hen egg lysozyme was monitored with and without substrate to
      verify that a carbohydrate can provide sufficiently stable protection of the
      amide hydrogen atoms in a protein's backbone from exchange with deuterated
      solvent. The substrate protected a number of amide hydrogens from exchange,
      implying that protein-carbohydrate binding systems will be compatible with amide
      exchange-MS. Endopolygalacturonase-II (EPG-II) from Aspergillus niger, a pectin
      degrading enzyme, was chosen as the first carbohydrate-binding system to be
      extensively studied using quenched amide exchange-MS. Monitoring the changes in
      deuterium incorporation of EPG-II in the presence and absence of an oligomer of
      galacturonic acid implied the location of substrate binding. This study
      demonstrates the ability of amide exchange-MS to investigate protein-carbohydrate
      interactions.

PMID- 12203251
TI  - A novel structural analysis of glycerophosphocholines as TFA/K(+) adducts by
      electrospray ionization ion trap tandem mass spectrometry.
AB  - When collisionally activated dissociation (CAD) of glycerophosphocholine (GPC)
      species is examined using quadrupole ion trap mass spectrometry (QITMS), the
      spectral patterns differ from those obtained using sector or quadrupole mass
      spectrometry. Methods employed in the structural analysis of GPCs using a sector
      or quadrupole mass spectrometers are not necessarily useful for an ion trap mass
      spectrometer. A novel method is presented for structurally analyzing GPCs that
      involves the CAD of trifluoroacetic acid (TFA) adducts of kaliated GPCs.
      Solutions of GPCs in 0.1% TFA/methanol were electrosprayed to produce precursor
      ions by attaching a trifluoroacetic acid (TFA) molecule to a kaliated GPC
      molecule. The CAD-MS/MS spectra obtained by QITMS revealed a dramatic increase in
      the abundance of fragment ions, corresponding to the losses of sn-1 and sn-2
      fatty acyl substituents. A preferential loss of the sn-1 fatty acyl group over
      the loss of the sn-2 fatty acyl group was observed among the GPC standards
      examined. A GPC extract from egg yolk was directly analyzed by this method
      without prior separation. The identities and positions of fatty acyl substituents
      of over 20 GPC species were identified. Some isomers present in very low relative
      abundance, which could not be analyzed by QITMS/MS using other ions as
      precursors, were identified by the TFA attachment method.

PMID- 12203252
TI  - A high-performance liquid chromatography/tandem mass spectrometric screening
      method for eight synthetic corticosteroids in bovine feces and the simultaneous
      differentiation between dexamethasone and betamethasone.
AB  - A screening method was developed to monitor the illegal use of synthetic
      corticosteroids in cattle. Diethyl ether extracts from spiked feces samples were
      cleaned-up by solid phase extraction followed by semipreparative reversed-phase
      chromatography (RPC). The fraction containing the corticosteroids was derivatized
      with ethoxyamine hydrochloride. The corresponding ethoximes were separated using
      silica-based C18 RPC and analyzed on-line in an ion trap mass spectrometer using
      atmospheric pressure positive chemical ionization. Ethoxime derivatives of
      dexamethasone and betamethasone were baseline resolved, allowing for the
      simultaneous mass spectrometric differentiation of both epimers in bovine feces
      by conventional non-chiral chromatography. At the lowest level tested (1 micro
      g/kg), corticosteroids (except triamcinolone) could be identified in compliance
      with the recent European criteria for residue identification. The quantitative
      performance of the method was best at residue levels > or = 2 micro g/kg.

PMID- 12203255
TI  - Identification of compound classes in soil and peat fulvic acids as observed by
      electrospray ionization tandem mass spectrometry.
AB  - Soil and peat fulvic acids obtained from the International Humic Substances
      Society were fractionated by their solubility in methanol and analyzed by
      electrospray ionization tandem mass spectrometry. Precursor and product ion
      experiments produced mass spectra that indicated the presence of benzene, phenol,
      dihydroxy benzene, furan and thiophene carboxylic acids. Standards were used to
      substantiate the fragmentation patterns observed in the product ion spectra of
      the fulvic acid samples. This study makes significant progress into the direct
      identification of individual compounds in humic substances using a non
      degradation technique.

PMID- 12203257
TI  - Khat: pharmacological and medical aspects and its social use in Yemen.
AB  - Fresh leaves of the khat tree (Catha edulis Forsk.) are chewed for their euphoric
      properties in East Africa and parts of the Middle East, such as The Yemen. This
      review describes the history, cultivation and constituents of khat, and the
      social aspects of khat chewing in Yemen. The major pharmacologically active
      constituent of the fresh leaves is (--)-S-cathinone. The pharmacology of (--)-S
      cathinone in the central nervous system and the peripheral effects are described.
      (--)-S-Cathinone is regarded as an amphetamine-like sympathomimetic amine and
      this mechanism of action is discussed in relation to the central stimulant
      actions and the cardiovascular effects of increasing blood pressure and heart
      rate. The risk factors associated with khat chewing are described, with emphasis
      on the reported increased incidence of acute myocardial infarction.

PMID- 12203258
TI  - Estrogenic activity of Nigella damascena extracts, evaluated using a recombinant
      yeast screen.
AB  - We used the yeast estrogen screen (YES) containing a human estrogen receptor to
      evaluate the estrogenic activity of extracts obtained from Nigella damascena
      seeds. Alcohol extracts obtained by direct extraction of seeds showed a low
      estrogenic activity, while the alcohol extract obtained after extraction with
      solvents of increasing polarity showed a strong estrogenic activity. This
      suggests the presence in Nigella of polar components whose activity can be
      clearly demonstrated after previous elimination of interacting apolar components
      that may mask the activity of more polar components. The response of both alcohol
      fractions follow a bell-shaped curve indicating a concentration-dependent
      relationship.

PMID- 12203259
TI  - Bioactivity studies on beta-sitosterol and its glucoside.
AB  - Beta-sitosterol and beta-sitosteryl-beta-D-glucoside were isolated as analgesic
      constituents from the leaves of Mentha cordifolia Opiz. The acetic acid-induced
      writhing test showed that beta-sitosterol and beta-sitosteryl-beta-D-glucoside
      decreased the number of squirms induced by acetic acid by 70.0% and 73.0%,
      respectively, at a dose of 100 mg / kg mouse. Statistical analysis using the
      Kruskall Wallis one-way analysis of variance by ranks showed that these isolates
      approximate the analgesic activity of mefenamic acid at a 0.001 level of
      significance. The hot plate method confirmed their analgesic activities, as beta
      sitosterol and beta-sitosteryl-beta-D-glucoside exhibited a 300% and 157%
      increase in pain tolerance, respectively, while mefenamic acid, a known
      analgesic, showed a 171% increase. Neither isolate exhibited antiinflammatory
      activity using the carrageenan-induced mouse paw oedema assay. Beta-sitosterol
      also exhibited anthelminthic and antimutagenic activities. In vitro tests using
      live Ascaris suum as test animals showed that the behaviour of worms treated with
      beta-sitosterol approximated that of the positive controls, Combantrin and
      Antiox. An in vivo micronucleus test showed that beta-sitosterol inhibited the
      mutagenicity of tetracycline by 65.3% at a dose of 0.5 mg /kg mouse. At the same
      dose, it did not exhibit chromosome-breaking activity.

PMID- 12203260
TI  - Inhibitory effects of Korean medicinal plants and camelliatannin H from Camellia
      japonica on human immunodeficiency virus type 1 protease.
AB  - To identify substances with anti-human immunodeficiency virus (HIV) activity in
      traditional medicines, 101 extracts of Korean medicinal plants were screened for
      their inhibitory effects on HIV type 1 protease (PR). The enzyme activity was
      determined by HPLC. Of the extracts tested, strong inhibitory effects were
      observed in the acetone extracts of the pericarp and leaves of Camellia japonica,
      the water extract of the leaves of Sageretia theezans and the methanol extract of
      the aerial part of Sophora flavescens. Camelliatannin H from the pericarp of C.
      japonica, showed a potent inhibitory activity on HIV-1 PR with IC(50) of 0.9
      microM.

PMID- 12203261
TI  - The acetone soluble fraction from bark extract of Stryphnodendron adstringens
      (Mart.) coville inhibits gastric acid secretion and experimental gastric
      ulceration in rats.
AB  - The acetone soluble fraction from a crude methanol extract of Stryphnodendron
      adstringens stem bark (AFSAB) was evaluated in acute (ethanol, indomethacin and
      hypothermic restraint-stress) and chronic (acetic acid) models of gastric
      ulceration and on basal and bethanechol-stimulated gastric acid secretion in
      rats. Rats pretreated orally with AFSAB at doses of 400 and 800 mg/kg showed
      significant decreases of gastric lesion scores in ethanol (62% and 98%) and
      hypothermic restraint-stress (89% and 88%) models but exerted no significant
      influence on indomethacin-induced acute or acetic acid-induced chronic
      ulceration. In pylorus-ligated rats, AFSAB significantly decreased the basal as
      well as bethanechol-stimulated gastric secretory volume and the total acidity
      with an elevated pH value. AFSAB failed to modify the gastric mucus and the
      gastric wall nonprotein-sulphydryl content. These results point to a possible
      antisecretory effect of AFSAB which account for the observed antiulcer activity
      in ethanol and hypothermic restraint-stress induced models of acute gastric
      ulceration.

PMID- 12203262
TI  - In vitro activity of Triclisia patens and some bisbenzylisoquinoline alkaloids
      against Leishmania donovani and Trypanosoma brucei brucei.
AB  - In the search for antiprotozoal compounds from natural sources, Triclisia patens
      displayed activity against L. donovani promastigotes (IC(50) = 1.5 microg/mL) and
      T. b. brucei blood stream trypomastigote forms (IC(50) = 31.25 microg/mL). In
      addition, a total of 20 bisbenzylisoquinoline alkaloids were screened for
      antileishmanial and antitrypanosomal activity in vitro. Fangchinoline (IC(50) =
      0.39 microM) was found to be as active as the standard pentamidine against
      Leishmania donovani promastigotes. Phaeanthine was three-fold more active (IC(50)
      = 2.41 microM; 1.5 microg/mL) than the standard drug Pentostam against L.
      donovani amastigotes, but at this concentration was toxic to murine macrophages.
      In contrast, cocsoline (IC(50) = 12.3 microM; 6.76 microg/mL) was as active as
      Pentostam, and was not toxic to macrophages at this concentration. Thalisopidine
      showed the strongest activity (IC(50) = 1.14 microM) against Trypanosoma brucei
      brucei blood stream form trypomastigotes, but was less active than pentamidine.

PMID- 12203263
TI  - Jasmine absolute (Jasminum grandiflora L.) and its mode of action on guinea-pig
      ileum in vitro.
AB  - Jasmine (Jasminum grandiflorum L.) is used in aromatherapy as a holistic
      treatment for apathy, hysteria, uterine disorders and childbirth, muscle
      relaxation and coughs. Its stimulant nature, on inhalation, has been shown both
      in animals and man. Jasmine has a spasmolytic activity on guinea-pig ileum and
      rat uterus in vitro. The mechanism of action of the spasmolytic activity, studied
      in vitro using a guinea-pig ileum smooth muscle preparation, was postsynaptic and
      not atropine-like. The spasmolytic effect of jasmine absolute was most likely to
      be mediated through cAMP, and not through cGMP. The mode of action in vitro
      resembled that of geranium, lavender and peppermint oils. The contradictory
      effect in vitro and in vivo is probably due to the solely physiological effects
      of jasmine absolute in vitro (producing a relaxation) compared with that in vivo,
      where it has a strong psychological input, producing a stimulant effect in man
      and enhanced movement in animals.

PMID- 12203264
TI  - In vitro anti-hepatoma activity of fifteen natural medicines from Canada.
AB  - Fifteen crude drugs, Stellaria media Cyrill. (Caryophyllaceae), Calendula
      officinalis L. (Compositae), Achillea millefolium L. (Compositae), Verbascum
      thapsus L. (Scrophulariaceae), Plantago major L. (Plantaginaceae), Borago
      officinalis L. (Boraginaceae), Satureja hortensis L. (Labiatae), Coptis
      groenlandica Salisb. (Ranunculaceae), Cassia angustifolia Vahl. (Leguminosae),
      Origanum majorana L. (Labiatae), Centella asiatica L. (Umbelliferae),
      Caulophyllum thalictroides Mich. (Berberidaceae), Picea rubens Sargent.
      (Pinaceae), Rhamnus purshiana D.C. (Rhamnaceae) and Hibiscus sabdariffa L.
      (Malvaceae), which have been used as folk medicine in Canada, were evaluated for
      their anti-hepatoma activity on five human liver-cancer cell lines, i.e.
      HepG2/C3A, SK-HEP-1, HA22T/VGH, Hep3B and PLC/PRF/5. The samples were examined by
      in vitro evaluation for their cytotoxicity. The results showed that the effects
      of crude drugs on hepatitis B virus genome-containing cell lines were different
      from those against non hepatitis B virus genome-containing cell lines. C.
      groenlandica was observed to be the most effective against the growth of all five
      cell lines and its chemotherapeutic values will be of interest for further
      studies.

PMID- 12203265
TI  - Antimycobacterial physalins from Physalis angulata L. (Solanaceae).
AB  - Crude extracts and fractions from aerial parts of Physalis angulata have been
      bioassayed for antimycobacterial activity. Fraction A1-29-12 containing physalins
      B, F and D exhibited a minimum inhibitory concentration value (MIC) against
      Mycobacterium tuberculosis H(37)Rv strain of 32 microg/mL. Purified physalin B
      and physalin D were also tested showing MIC values against Mycobacterium
      tuberculosis H(37)Rv strain of > 128 microg/mL and 32 microg/mL respectively,
      suggesting that physalin D plays a relevant role in the antimycobacterial
      activity displayed. Structural elucidation of both physalins D and B was based on
      detailed (13)C and (1)H NMR spectral analysis with the aid of 2D-correlation
      spectroscopy ((1)H-(1)H, COSY, HSQC and HMBC). The assignment of the (13)C
      chemical shift for physalin D is reported here for the first time.

PMID- 12203266
TI  - Extract of Yi Zhi Fang improves learning and memory behaviours of mice and its
      possible mechanisms.
AB  - The effects of Yi Zhi Fang extract (YZF) on learning and memory performances were
      investigated in mice using passive avoidance tasks. Oral administration of YZF
      improved learning and memory disorders induced by chemicals in both normal and
      senile mice. The acetylcholine (Ach) concentration, the muscarinic Ach receptors
      (M-R) and the monoamine oxidase B (MAO-B) activities were analysed by a
      radioimmunoassay, a radioligand receptor binding assay and UV spectrophotometry,
      respectively, using senile decapitated mice. The oral administration of YZF to
      the senile mice increased the M-R concentration, while the concentration of Ach
      and the activity of MAO-B decreased in senile mice brains. From these results it
      is evident that YZF promotes the function of the central cholinergic system and
      inhibits the activity of MAO-B in mice brains resulting in an enhancement of
      learning and memory.

PMID- 12203267
TI  - Anxiolytic and anticonvulsive activity of Sesbania grandiflora leaves in
      experimental animals.
AB  - Various parts of Sesbania grandiflora have been used in the Indian system of
      medicine, in particular, the leaves of S. grandiflora are used in Ayurveda for
      the treatment of epileptic fits. In the present study we have evaluated the
      anticonvulsive activity of S. grandiflora leaves using a variety of animal models
      of convulsions. Bioassay guided separation was also carried out to identify the
      fraction possessing anticonvulsant activity. The benzene:ethyl acetate fraction
      (BE) of the acetone soluble part of a petroleum ether extract significantly
      delayed the onset of convulsions in pentylenetetrazol (PTZ) and strychnine (STR)-
      induced seizures in mice and reduced the duration of tonic hindleg extension in
      the maximum electroconvulsive shock (MES) induced seizures in mice. The BE
      contained a triterpene as a major component. In addition, the BE also inhibited
      electrically induced kindled seizures in mice and lithium-pilocarpine-induced
      status epilepticus in rats. It prolonged the duration of sleep induced by
      pentobarbital and antagonized the effect of D-amphetamine. Mice treated with BE
      preferred to remain in the open arm of the elevated plus maze indicating
      anxiolytic activity. The BE raised the brain contents of gamma-aminobutyric acid
      and serotonin. Thus the triterpene containing fraction of S. grandiflora exhibits
      a wide spectrum of anticonvulsant profile and anxiolytic activity.

PMID- 12203268
TI  - Antioxidant and non-toxic properties of Piper betle leaf extract: in vitro and in
      vivo studies.
AB  - Piper betle leaves are used in folk medicine for the treatment of various
      disorders and is commonly chewed among Asians. The present study investigates the
      protective efficacy of P. betle leaf extract. The presence of the extract
      inhibited the radiation induced lipid peroxidation process effectively. This
      could be attributed to its ability to scavenge free radicals involved in
      initiation and propagation steps. Oral supplementation with extract (1, 5 and 10
      mg/kg) was administered daily for 2 weeks to Swiss albino mice and the hepatic
      antioxidant status was analysed. The GSH content was enhanced and no appreciable
      change was found in the levels of oxidative damage in terms of lipid
      peroxidation. Also, the specific activity of SOD increased in a dose dependent
      manner. These factors indicate the elevation of antioxidant status in the
      animals. The effect on the glyoxalase system which is considered to be activated
      under stress conditions was also investigated. Our findings did not observe any
      significant change in gly I and gly II activities, implying a non-stress
      condition after oral treatment of the extract. The present study indicates the
      antioxidant activity of P. betle leaf extract and its potential to elevate the
      antioxidant status.

PMID- 12203269
TI  - In vitro antioxidant activity of non-cultivated vegetables of ethnic Albanians in
      southern Italy.
AB  - A total of 27 extracts from non-cultivated and weedy vegetables traditionally
      consumed by ethnic Albanians (Arbereshe) in the Vulture area (southern Italy)
      were tested for their free radical scavenging activity (FRSA) in the DPPH (1,1
      diphenyl-2-picrylhydrazil radical) screening assay, for their in vitro non
      enzymatic inhibition of bovine brain lipid peroxidation and for their inhibition
      of xanthine oxidase (XO). In both antioxidant assays strong activity was shown
      for Leopoldia comosa (bulbs, syn.: Muscari comosum) and Centaurea calcitrapa
      (young whorls). In the lipid peroxidation assay, extracts from leaves of Origanum
      heracleoticum, Urtica dioica and Tordylium apulum showed a remarkable inhibitory
      activity (> 50%), too. In the case of Leopoldia comosa and Origanum heracleoticum
      this activity was comparable to quercetin (at a concentration of 50 microM) and
      Rhodiola rosea extract. Extracts from non-cultivated Cichorium intybus,
      Chondrilla juncea and Stellaria media showed strong in vitro inhibition of
      xanthine oxidase, with an activity higher than that of a reference extract from
      Ledum groenlandicum. These findings suggest that weedy vegetables may be useful
      antioxidants of interest in the prevention of ageing related diseases, CNS
      disorders and as potential sources of phytomedicines against hyperuricaemia and
      gout.

PMID- 12203270
TI  - Effect of Acanthopanax senticosus Harms on biogenic monoamine levels in the rat
      brain.
AB  - The extract of the stem bark of Acanthopanax senticosus Harms (ASH) is known to
      have healing and protective effects on stress-induced disturbance of mental
      status. We have analysed whether a single or chronic (2 week) administration of
      ASH can affect concentrations of noradrenaline (NA), dopamine (DA) and their
      metabolites in the normal rat brain. A single p.o. administration of ASH elevated
      the NA and DA levels in the whole brain of rats in a dose-dependent manner. A
      single or 2 week administration of ASH (500 mg/kg) showed a marked increase in
      the DA level only in the striatum. However, NA levels were increased by a single
      dose of ASH in a wide range of brain regions such as the cortex, hypothalamus,
      striatum, hippocampus, substantia nigra and pons. When administered for 2 weeks
      no increase in NA levels was seen in these brain regions, except for an increase
      in the frontal cortex and anterior hypothalamus. The present results suggest that
      ASH may act by regulating NA and DA levels in specific brain regions related to
      stress response and Parkinson's disease.

PMID- 12203271
TI  - Hypolipidaemic activity of seaweed from Karachi coast.
AB  - During the present study, ethanol extracts of five seaweed species Solieria
      robusta, Iyengaria stellata, Colpomenia sinuosa, Spatoglossum asperum and
      Caulerpa racemosa at 10 mg/ 200 g body weight were tested for their
      hypolipidaemic activity. All the species significantly decreased the serum total
      cholesterol, triglyceride and low density lipoprotein cholesterol levels in
      normal, triton-induced and diet-induced hyperlipidaemic rats. Solieria robusta
      was found to be the most effective in reducing the lipid profile, particularly in
      diet-induced hyperlipidaemic rats. A beneficial effect of the ethanol extract of
      S. asperum was also found on cardiac and liver enzymes in diet-induced
      hyperlipidaemic rats.

PMID- 12203272
TI  - Scavenger activity of Allium psekemense B. Fedtsch.
AB  - In the present study the antioxidative properties of the bulbs, leaves and stalks
      of Allium psekemense B. Fedtsch were investigated. The activities of antioxidant
      enzymes (superoxide dismutase, catalase, peroxidase, glutathione peroxidase),
      quantities of malonyldialdehyde, superoxide and hydroxyl radicals and reduced
      glutathione and also the content of total flavonoids, chlorophylls a and b,
      carotenoids, vitamin C and soluble proteins were determined. The results indicate
      that extracts from all plant organs exhibited antioxidant activity. The highest
      antioxidant activity was observed in the leaves. Furthermore, the ESR signal of
      DMPO-OH radical adducts in the presence of the leaf phosphate buffer (pH 7)
      extract was reduced by 54.3%.

PMID- 12203273
TI  - Effect of Ginkgo biloba extract on beta-adrenergic receptors in different rat
      brain regions.
AB  - The effect of oral administration of Ginkgo biloba extract at a dose of 90 mg/kg
      for 7 consecutive days on rat brain beta-adrenergic receptors in the frontal
      cortex, hippocampus, striatum and hypothalamus was studied. Ginkgo biloba
      treatment induced a significant decrease in the density (B(max)) of beta
      adrenoreceptors in the frontal cortex and hippocampus. It has been suggested that
      modulation of the beta-adrenergic system is implicated in the favourable effects
      of Ginkgo biloba extracts on learning and memory.

PMID- 12203274
TI  - Aloe arborescens extract inhibits TPA-induced ear oedema, putrescine increase and
      tumour promotion in mouse skin.
AB  - The ethyl acetate extract of the acetone-soluble Aloe arborescens fraction was
      found to inhibit 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced ear oedema,
      putrescine increase and tumour promotion in mouse skin. Chromatographic analyses
      of this extract revealed that phenolic compounds such as aloenin, barbaloin and
      isobarbaloin could be useful as cancer chemopreventive agents against tumour
      promotion.

PMID- 12203275
TI  - Susceptibility of some clinical isolates of Staphylococcus aureus to bioactive
      column fractions from the lichen Ramalina farinacea (L.) Ach.
AB  - The antimicrobial activities of two bioactive column chromatographic fractions
      (RF1 and RF2) from the lichen Ramalina farinacea (L.) were evaluated against 15
      clinical isolates of Staphylococcus aureus. The susceptibility pattern of the
      isolates towards tetracycline (TCN) and ampicillin (AMP) was similarly -evaluated
      for comparison purposes. The results show that RF1 and RF2 with an MIC(90) (
      minimum -inhibitory concentration against 90% of the isolates) of 535.5 and 317
      microg/mL respectively, performed generally better than TCN and AMP with an
      MIC(90) of 976.5 and 357 microg/mL respectively.

PMID- 12203276
TI  - Evaluation of the antimicrobial potential of medicinal plants from the Ivory
      Coast.
AB  - A total of 148 crude ethanol extracts from 115 plant species were tested in vitro
      against Gram-negative strains (Escherichia coli, Pseudomonas aeruginosa) and the
      Gram-positive Staphylococcus aureus and Enterococcus faecalis. Moreover, they
      were submitted to antifungal assays against Candida albicans and Cladosporium
      cucumerinum, a human and a plant pathogenic microorganism, respectively, known to
      be good indicators of antifungal activity. No activity was detected against the
      Gram-negative bacteria, while 14.8% and 10.8% of the extracts showed Gram
      positive bactericidal or bacteriostatic effects on S. aureus and E. faecalis,
      respectively. An antifungal activity was observed with 15 extracts (10.1%). Two
      species were particularly active against the fungi: Dioscorea minutiflora and
      Erythrina vogelii. The young tubers of D. minutiflora contain metabolites with a
      specific effect on fungi and were not active against the bacteria. On the other
      hand, E. vogelii was highly effective against the Gram-positive bacteria and the
      fungi.

PMID- 12203277
TI  - Enhancing the ion-transport selectivity of multilayer polyelectrolyte membranes.
AB  - Alternating adsorption of polycations and polyanions on permeable supports
      provides a convenient and versatile method for preparing composite membranes with
      selective, ultrathin polyelectrolyte skins. Control over charge and composition
      in the polyelectrolyte skin allows highly selective separation of ions according
      to charge, size, or hydration energy.

PMID- 12203278
TI  - From N(2) and O(2) to N(4) and O(4): pneumatic chemistry in the 21st century.
AB  - A brief account is given of the theoretical and experimental endeavors that span
      the last decade and eventually led to the discovery of N(4) and O(4), which have
      been actively sought for their fundamental interest and their relevance to
      atmospheric sciences and the development of high energy density materials (HEDM).
      The discovery and characterization of N(4) and O(4) as metastable species with
      lifetimes exceeding 1 micros in the isolated gas state have finally been achieved
      utilizing neutralization-reionization mass spectrometry (NRMS), a powerful
      technique based on collisional redox processes. The principles of NRMS,
      experimental outline, main features, and limitations are succinctly examined in
      comparison with other current approaches to the detection of metastable, short
      lived neutral species.

PMID- 12203279
TI  - Transmission surface-plasmon resonance (T-SPR) measurements for monitoring
      adsorption on ultrathin gold island films.
AB  - Evaporation of ultrathin (1.3-10 nm nominal thickness) gold films onto quartz or
      mica leads to the formation of a layer of rather uniform gold islands on the
      transparent support. The morphology of ultrathin gold island films of various
      thicknesses was studied by using atomic force microscopy (AFM) and scanning
      electron microscopy (SEM) imaging. The surface plasmon (SP) absorption
      characteristic of such films is highly sensitive to the surrounding medium, with
      the plasmon band changing in intensity and wavelength upon binding of various
      molecules to the surface. The binding process can be monitored quantitatively by
      measuring the changes in the gold SP absorption, by using transmission UV/Vis
      spectroscopy. The method, termed transmission surface plasmon resonance (T-SPR)
      spectroscopy, is shown to be applicable to both chemically and physically
      adsorbed molecules, in liquid or gas phase, with measurements carried out either
      ex situ or in situ (real-time measurements) using a variety of molecular probes.
      Binding to a preformed molecular layer on the Au surface produces a similar
      response, suggesting the possible use of T-SPR for selective sensing. The
      sensitivity of T-SPR spectroscopy in detecting molecular binding to the gold
      depends strongly on the film preparation conditions, and may be comparable to
      that obtained in surface plasmon resonance (SPR) sensing.

PMID- 12203280
TI  - Single-crystal structures of polyphenylene dendrimers.
AB  - A series of first-generation polyphenylene dendrimers based on three different
      cores were prepared by Diels-Alder cycloaddition and their single-crystal
      structures were determined. Consisting exclusively of interlocked, twisted phenyl
      rings, these polyphenylene nanostructures have exciting structural and dynamic
      properties. Single crystals of dendrimers, suitable for X-ray structure analysis,
      were grown from different solvent mixtures by slow evaporation at room
      temperature. It should be pointed out that one of the described polyphenylene
      dendrimers represents up to now the biggest oligophenylene nanostructure from
      which crystallographic data is available.

PMID- 12203281
TI  - Studies on the selective transport of organic compounds by using ionic liquids as
      novel supported liquid membranes.
AB  - The possibility of using room-temperature ionic liquids (RTILs) in bulk
      (nonsupported) and supported liquid membranes for the selective transport of
      organic molecules is demonstrated. A systematic selective transport study, in
      which 1,4-dioxane, propan-1-ol, butan-1-ol, cyclohexanol, cyclohexanone,
      morpholine, and methylmorpholine serve as a model seven-component mixture of
      representative organic compounds, and in which four RTILs based on the 1-n-alkyl
      3-methylimidazolium cation (n-butyl, n-octyl, and n-decyl) are used together with
      the anions PF(6)(-) or BF(4)(-), immobilized in five different supporting
      membranes, confirms that the combination of the selected RTILs with the
      supporting membranes is crucial to achieve good selectivity for a specific
      solute. The use of the RTIL 1-n-butyl-3-methylimidazolium hexafluorophosphate,
      immobilized in a polyvinylidene fluoride membrane, allows an extremely highly
      selective transport of secondary amines over tertiary amines (up to a 55:1
      ratio). The selective transport of a given solute through the RTIL/membrane
      system results from the high partitioning of the solute to the liquid membrane
      phase which, in the case of amines, is rationalized mainly by the formation of a
      preferential substrate/H[bond]C(2) hydrogen bonding to the imidazolium cation.

PMID- 12203283
TI  - Template-synthesized nanotubes for chemical separations and analysis.
AB  - We have developed a new class of synthetic membranes that consist of a porous
      polymeric support that contains an ensemble of gold nanotubes that span the
      thickness of the support membrane. The support is a commercially-available
      microporous polycarbonate filter with cylindrical nanoscopic pores. The gold
      nanotubes are prepared by electroless deposition of Au onto the pore walls, that
      is, the pores acts as templates for the nanotubes. We have shown that by
      controlling the Au deposition time, Au nanotubes that have effective inside
      diameters of molecular dimensions (<1 nm) can be prepared. These nanotube
      membranes can be used to cleanly separate small molecules on the basis of
      molecular size. Furthermore, use of these membranes as a novel electrochemical
      sensor is also discussed. This new sensing scheme involves applying a constant
      potential across the Au nanotube membrane and measuring the drop in the
      transmembrane current upon the addition of the analyte. This paper reviews our
      recent progress on size-based based transport selectivity and sensor applications
      in this new class of membranes.

PMID- 12203284
TI  - Environmental performance metrics for daily use in synthetic chemistry.
AB  - A simple quantitative approach to enable chemists to compare alternative chemical
      syntheses on the lab bench with respect to their resource usage and their
      potential environmental impact is proposed; this may be useful for the systematic
      design of more sustainable processes. We consider as metrics the mass index S(-1)
      and the environmental factor E to characterize quantitatively the reaction input
      and output, respectively. The potential environmental impact is estimated by
      using easily available data of each compound of the feed and of each compound of
      the waste. The calculations can easily be performed using EATOS-environmental
      assessment tool for organic syntheses.

PMID- 12203285
TI  - Novel flexible frameworks of porous cobalt(II) coordination polymers that show
      selective guest adsorption based on the switching of hydrogen-bond pairs of amide
      groups.
AB  - Four porous crystalline coordination polymers with two-dimensional frameworks of
      a double-edged axe-shaped motif, [[Co(NCS)(2)(3-pia)(2)] x 2 EtOH.11 H(2)O](n) (1
      a), [[Co(NCS)(2)(3-pia)(2)] x 4 Me(2)CO](n) (3 a), [[Co(NCS)(2)(3-pia)(2)] x 4T
      HF](n) (3 b) and [[Co(NCS)(2)(3-pna)(2)](n)] (5), have been synthesized by the
      reaction of cobalt(II) thiocyanate with N-(3-pyridyl)isonicotinamide (3-pia) or N
      (3-pyridyl)nicotinamide (3-pna). X-ray crystallographic characterization reveals
      that adjacent layers are stacked such that channels are created, except in 5. The
      channels form a hydrogen-bonded interior for guest molecules; in practice, 1 a
      contains ethanol and water molecules as guests in the channels with hydrogen
      bonds, whereas 3 b (3 a) contains tetrahydrofuran (acetone) molecules. In 1 a,
      the "double-edged axe-shaped" motifs in adjacent sheets are not located over the
      top of each other, while the motifs in 3 b stack so perfectly as to overlap each
      other in an edge-to-edge fashion. This subtle change in the three-dimensional
      framework is associated with the template effect of the guests. Compound 5 has no
      guest molecules and, therefore, the amide groups in one sheet are used for
      hydrogen-bonding links with adjacent sheets. Removal of the guest molecules from
      1 a and 3 b (3 a) causes a structural conversion accompanied by a color change.
      Pink 1 a cannot retain its original framework and changes into a blue amorphous
      compound. On the other hand, the framework of pink 3 b (3 a) is transformed to a
      new crystalline framework of violet 4. Interestingly, 4 reverts to the original
      pink crystals of 3 b (3 a) when it is exposed to THF (or acetone) vapor.
      Spectroscopic measurements (visible, EPR, and IR) provide a clue to the crystal
      to-crystal transformation; on removal of the guests, the amide groups are used to
      form the beta sheet-type hydrogen bonding between the sheets, and thus the
      framework withstands significant stress on removal of guest molecules. This
      mechanism is attributed to the arrangement of the adjacent sheets so suited in
      regularity that the beta sheet-type structure forms efficiently. The apohost 4
      does not adsorb cyclopentane, showing a guest selectivity that, in addition to
      size, hydrogen-bonding capability is required for the guest molecules. The
      obtained compound is categorized as a member of a new generation of compounds
      tending towards functional porous coordination polymers.

PMID- 12203286
TI  - Novel extended tetrathiafulvalenes based on acetylenic spacers: synthesis and
      electronic properties.
AB  - A selection of mono- and diacetylenic dithiafulvalenes was synthesized and
      employed for the construction of extended tetrathiafulvalenes (TTFs) with hexa
      2,4-diyne-1,6-diylidene or deca-2,4,6,8-tetrayne-1,10-diylidene spacers between
      the two 1,3-dithiole rings. By stepwise acetylenic scaffolding using (E)-1,2
      diethynylethene (DEE) building blocks, an extended TTF containing a total of 18
      C(sp) and C(sp(2)) atoms in the spacer was prepared. The versatility of the
      acetylenic dithiafulvene modules was also established by the efficient synthesis
      of a thiophene-spaced TTF, employing a palladium-catalyzed cross-coupling
      reaction. The developed synthetic protocols allow functionalization of the
      extended TTFs in three general ways: with 1) peripheral substituents on the
      fulvalene cores, 2) alkynyl moieties laterally appended to the spacer, and 3)
      cobalt clusters involving acetylenic moieties. Strong chromophoric properties of
      the extended TTFs were revealed by linear and nonlinear optical spectroscopies.
      Extensive electrochemical studies and calculations on these compounds are also
      reported, as well as X-ray crystallographic analyses.

PMID- 12203287
TI  - Metal- and ligand-directed one-pot syntheses, crystal structures, and properties
      of novel oxo-centered tetra- and hexametallic clusters.
AB  - Starting from closely related metal-ligand combinations, completely different
      oligomeric metal clusters are synthesized. Whereas, picoline-tetrazolylamide
      HL(1) (1) and zinc or nickel acetate afforded [2x2] grids [M(4)(L(1))(8)] (2),
      slightly different N-(2-methylthiazole-5-yl)-thiazole-2-carboxamide HL(2) (5 a)
      and nickel acetate yielded the monometallic complex [Ni(L(2))(2)(OH(2))(2)] (6).
      In contrast, reaction of 5 a with zinc acetate produced the tetrametallic zinc
      cluster [Zn(4)O(L(2))(4)(OAc)(2)] (7). Even more surprising, when 3-methyl
      substituted HL(3) (5 b) instead of 2-methyl-substituted HL(2) (5 a) was allowed
      to react under identical conditions with zinc acetate, the cluster
      [Zn(4)O(L(3))(4)Cl(2)] (8) crystallized from dichloromethane. Clusters 7 and 8
      are isostructural. As for 7, in 8 two of the edges of the tetrahedron of zinc
      ions are doubly bridged, two are singly bridged, and the other two are
      nonbridged. On the other hand, when iron(II) acetate under aerobic conditions was
      allowed to react with 5 a, the unprecedented complex
      [[Fe(3)O(L(2))(2)(OAc)(4)](2)O] (9) was isolated. Cluster 9 is composed of two
      trimetallic, triangular mu(3)-O(2-)-centered [Fe(3)O(L(2))(2)(OAc)(4)](+)
      modules, linked by an almost linear mu(2)-O(2-) bridge. The Mossbauer spectrum
      together with cyclic voltammetric and square-wave voltammetric measurements of 9
      are reported, and 6-9 were characterized unequivocally by single-crystal X-ray
      structure analyses.

PMID- 12203288
TI  - Intramolecular coupling of allyl carboxylates with allyl stannanes and allyl
      silanes: a new type of reductive elimination reaction?
AB  - The palladium-catalyzed intramolecular coupling of allyl stannanes with allyl
      carboxylates provides a general synthesis of five- and six-membered-ring
      carbocycles. The intramolecular coupling leads selectively to trans five-membered
      carbocycles and cis six-membered carbocycles, regardless of the cis or trans
      configuration of the allylic functions in the starting material. For example, the
      stereoselective synthesis of 10-epi-elemol demonstrated the cis configuration of
      the six-membered carbocycles. The related Oppolzer cyclization leads to lower
      yields, or fails completely, with substrates substituted at C-3 of the allyl
      and/or alkene terminus. The palladium-catalyzed intramolecular coupling of allyl
      silanes with allyl trifluoroacetates allows the synthesis of trans five-membered
      ring carbocycles and requires the use of a bicyclic phosphite as the ligand. DFT
      calculations suggest that the preferred pathway for the intramolecular
      allyl/allyl coupling is by formation of the Cbond;C bond between the C-3 termini
      of the allyl ligands of bis(eta(3)-allyl)palladium complexes.

PMID- 12203289
TI  - Probing the stereointegrity of Troger's base--a dynamic electrokinetic
      chromatographic study.
AB  - Under acidic conditions the enantiomers of Troger's base 1 (2,8-dimethyl-6 H,12 H
      5,11-methanodibenzo[b,f][1,5]diazozine) are subject to enantiomerization. During
      enantioselective dynamic electrokinetic chromatography using 10 mM hydroxypropyl
      beta-cyclodextrin as the chiral mobile phase additive in 50 mM tris/phosphate
      buffer at pH 2.2, enantiomerization of Troger's base gives rise to characteristic
      elution profiles featuring plateau formation and peak broadening. Introduction of
      a permanent positive charge attributed to quaternization in the monobenzylated
      derivative of Troger's base 2 (5-benzyl-2,8-dimethyl-6 H,12 H-5,11
      methanodibenzo[b,f][1,5]diazozinium bromide) decreases the enantiomerization
      barrier significantly. To determine the rate constants of enantiomerization the
      experimental chromatograms were evaluated by a direct calculation method and by
      using the computer simulation program ChromWin. From temperature-dependent
      measurements the Eyring activation parameters for 1 and 2 were determined: 1:
      DeltaG( not equal ) (298 K)=100.9+/-0.5 kJ mol(-1), DeltaH( not equal )=89.5+/
      2.0 kJ mol(-1), DeltaS( not equal )=-42+/-10 J K(-1) mol(-1); 2: DeltaG( not
      equal ) (298 K)=90.2+/-0.5 kJ mol(-1), DeltaH( not equal )=91.4+/-2.0 kJ mol(-1),
      DeltaS( not equal )=9.8+/-10 J K(-1) mol(-1).

PMID- 12203290
TI  - Radical para-benzoic acid derivatives: transmission of ferromagnetic interactions
      through hydrogen bonds at long distances.
AB  - Investigation of the transmission of magnetic interactions through hydrogen bonds
      has been carried out for two different benzoic acid derivatives which bear either
      a tert-butyl nitroxide (NOA) or a poly(chloro)triphenylmethyl (PTMA) radical
      moiety. In the solid state, both radical acids formed dimer aggregates by the
      complementary association of two carboxylic groups though hydrogen bonding. This
      association ensured that atoms with most spin density are separated from one
      another by more than 15 A. Thus, no competing through-space magnetic exchange
      interactions are expected in these dimers and, hence, they provide good models to
      investigate whether noncovalent hydrogen bonds play a role in the long-range
      transmission of magnetic interactions. The nature of the magnetic exchange
      interaction and their strengths within similar dimer aggregates in solution was
      assessed by electron spin resonance (ESR) spectroscopy. In the case of radical
      NOA, low-temperature ESR experiments showed a weak ferromagnetic interaction
      between the two radicals in the dimer aggregates (which have the same geometry as
      in the solid state). In contrast, the corresponding solution ESR study performed
      with radical PTMA did not lead to any conclusive results, as aggregates were
      formed by noncovalent interactions other than hydrogen bonds. However, the
      bulkiness of the poly(chloro)triphenylmethyl radical prevented interdimer
      contacts in the solid state between regions of high spin density. Hence, solid
      state measurements of the alpha phase of PTMA radical provided evidence of the
      intradimer interaction to confirm the transmission of a weak ferromagnetic
      interaction through the carboxylic acid bridges, as found for the NOA radical.
      Moreover, crystallization of the PTMA radical in presence of ethanol to form the
      beta phase of PTMA radical prevented the dimer formation; this resulted in the
      suppression of this interaction and provides further evidence of the magnetic
      exchange mechanism through noncovalent hydrogen bonds at long distances.

PMID- 12203291
TI  - A novel one-step approach for the preparation of alpha-amino acids, alpha-amino
      amides, and dipeptides from azetidine-2,3-diones.
AB  - A remarkable reaction of azetidine-2,3-diones with primary as well as secondary
      amines, and water is presented. Simply by varying the nucleophile, an
      unprecedented one-step synthesis of alpha-amino acids, alpha-amino amides, and
      dipeptides, was developed in both the racemic and optically pure forms. The
      current mechanistic hypothesis invokes a concerted process involving CO
      extrusion. However, a stepwise pathway can also account for these novel
      transformations.

PMID- 12203292
TI  - Formation of O3+ upon ionization of O2: the role of isomeric O4+ complexes.
AB  - The course of the reaction of electronically and vibronically excited metastable
      O(2) (+)((4)Pi(u), nu') ions with O(2), known to produce O(3) (+), was examined
      by the joint application of computational and mass spectrometric methods. The
      results show that the reaction does not proceed by a direct mechanism and that it
      involves instead the intermediacy of the [O(2) (+)((4)Pi(u)) x O(2)] and [O(3)
      (+)((4)A(2)) x O] complexes, both theoretically characterized, and the latter one
      positively identified by structurally diagnostic mass spectrometric techniques.
      The reaction is a potential source of stratospheric ozone, in that O(3) (+) ions
      are known to undergo efficient charge exchange with oxygen to yield neutral O(3).

PMID- 12203293
TI  - Electronic structure and nature of the ground state of the mixed-valence
      binuclear tetra(mu-1,8-naphthyridine-N,N')-bis(halogenonickel) tetraphenylborate
      complexes: experimental and DFT characterization.
AB  - The ground state electronic structure of the mixed-valence systems
      [Ni(2)(napy)(4)X(2)](BPh(4)) (napy=1,8-naphthyridine; X=Cl, Br, I) was studied
      with combined experimental (X-ray diffraction, temperature dependence of the
      magnetic susceptibility, and high-field EPR spectroscopy) and theoretical (DFT)
      methods. The zero-field splitting (zfs) ground S=3/2 spin state is axial with /D/
      approximately 3 cm(-1). The iodide derivative was found to be isostructural with
      the previously reported bromide complex, but not isomorphous. The compound
      crystallizes in the monoclinic system, space group P2(1)/n, with a=17.240(5),
      b=26.200(5), c=11.340(5) A, beta=101.320(5) degrees. DFT calculations were
      performed on the S=3/2 state to characterize the ground state potential energy
      surface as a function of the nuclear displacements. The molecules can thus be
      classified as Class III mixed-valence compounds with a computed delocalization
      parameter, B=3716, 3583, and 3261 cm(-1) for the Cl, Br, and I derivatives,
      respectively.

PMID- 12203294
TI  - Preparation and characterization of new room temperature ionic liquids.
AB  - A new series [C(n)O(m )mim][X] of imidazolium cation-based room temperature ionic
      liquids (RTILs), with ether and alcohol functional groups on the alkyl side-chain
      has been prepared. Some physical properties of these RTILs were measured, namely
      solubility in common solvents, viscosity and density. The solubility of LiCl,
      HgCl(2) and LaCl(3) in room temperature ionic liquids was also determined. The
      features of the solid-liquid phase transition were analysed, namely the glass
      transition temperature and the heat capacity jump associated with the transition
      from the non-equilibrium glass to the metastable supercooled liquid. These
      properties were compared with those reported for the 1-n-alkyl-3
      methylimidazolium [C(n )mim][X] series. While the density and solid-liquid phase
      transition properties are similar for both series, the new RTILs present a
      considerably lower viscosity and an increased ability to dissolve HgCl(2) and
      LaCl(3) (up to 16 times higher).

PMID- 12203295
TI  - Weak hydrogen bonding as a basis for concentration-dependent guest selectivity by
      a cyclophane host.
AB  - Crystalline inclusion complexes between the cyclophane 1 and three isomers of
      picoline and lutidine were grown and their properties and structures were studied
      by X-ray analysis, thermal gravimetry (TG), and differential scanning calorimetry
      (DSC). In competition experiments, the cyclophane host, which by itself is only
      able to form weak Cbond;H.acceptor hydrogen bonds, is able to discriminate
      between the different picoline or lutidine isomers, although in some cases a
      strong concentration dependence of the preferred isomer is observed. In the three
      component experiments, inclusion of 4-picoline is strongly favored when X(4
      picoline)>0.35-0.39. Very similar results were obtained in the lutidine series.
      The fact that 2,4-lutidine is favored when X(2,4-lutidine)>0.2 indicates that the
      host prefers the isomer with the methyl group in 4-position relative to the
      nitrogen atom. The selectivities observed can be explained based on the
      assignment of the inclusion complexes to different adduct classes. In the case of
      the picoline isomers, the preference of 4-picoline was in good agreement with the
      calculated lattice energies for this series. The present work also shows that
      caution is advisable when deducing selectivity of crystalline inclusion compounds
      from guest competition experiments.

PMID- 12203296
TI  - Control of lysine reactivity in four-helix bundle proteins by site-selective pKa
      depression: expanding the versatility of proteins by postsynthetic
      functionalization.
AB  - Five 42-residue polypeptides have been designed to fold into hairpin helix-loop
      helix motifs that dimerize to form four-helix bundles, and to serve as protein
      scaffolds for the elucidation at the molecular level of the principles that
      control and fine-tune lysine and ornithine reactivities in a protein context.
      Site-selective control of Lys and Orn reactivity provides a mechanism for
      addressing directly individual residues and is a prerequisite for the site
      selective functionalization of folded proteins. Several lysine and one ornithine
      residues were introduced on the surface and in the hydrophobic core of the folded
      motif. The reactivity of each residue was determined by measuring the degree of
      acylation of the trypsin cleaved fragments by HPLC and mass spectrometry. The
      most reactive residues were Orn34 and Lys19, both of which were located in d
      positions in the heptad repeat, and therefore in hydrophobic environments. Upon
      reaction of the helix-loop-helix dimer KA-I with one equivalent of mono-p
      nitrophenyl fumarate, Orn34 was acylated approximately three times more
      efficiently than Lys19, whereas Lys10 (b position), Lys15 (g position), and Lys33
      (c position) remained unmodified. In the sequence KA-I-A(15) Lys15 was replaced
      by an alanine residue and the selectivity of Orn34 over Lys19 increased to
      approximately a factor of six, probably because Lys15 had the capacity to reduce
      the pK(a) value of Lys19 and 85 % of site-selectively monoacylated product was
      obtained. The pH dependence of the acylation reaction was determined and showed
      that the pK(a) of the reactive residues were 9.3, more than a pK(a) unit below
      the magnitude of the corresponding residue in a solvent exposed position.
      Introducing Lys and Orn residues into a or d positions of the heptad repeat
      therefore serves as a mechanism of depressing their pK(a) to increase their
      reactivity site selectively. Extensive NMR and CD spectroscopic analyses showed
      that the sequences fold according to prediction.

PMID- 12203297
TI  - Formation of diphenylphosphanylbutadienyl complexes by insertion of two P
      coordinated alkynylphosphanes into a PtbondC6F5 bond: detection of intermediate
      and reaction products.
AB  - The reactions between cis-[M(C(6)F(5))(2)(PPh(2)CtriplebondCR)(2)] (M=Pt, Pd;
      R=Ph, tBu, Tol 2, 3) or cis
      [Pt(C(6)F(5))(2)(PPh(2)CtriplebondCR)(PPh(2)CtriplebondCtBu)] (R=Ph 4, Tol 5) and
      cis-[Pt(C(6)F(5))(2)(thf)(2)] 1 have been investigated. Whereas
      [M](PPh(2)CtriplebondCtBu)(2) ([M]=cis-M(C(6)F(5))(2)) is inert towards 1, the
      analogous reactions starting from [M](PPh(2)CtriplebondCR)(2) or
      [Pt](PPh(2)CtriplebondCR)(PPh(2)CtriplebondCtBu) (R=Ph, Tol) afford unusual
      binuclear species [Pt(C(6)F(5))(S)mu
      [C(R')dbondC(PPh(2))C(PPh(2))doublebondC(R)(C(6)F(5))]M(C(6)F(5))(2)] (R=R'=Ph,
      Tol, M=Pt 6 a,c, M=Pd 7 a,c; M=Pt, R'=tBu, R=Ph 8, Tol 9) containing a
      bis(diphenylphosphanyl)butadienyl bridging ligand formed by an unprecedented
      sequential insertion reaction of two P-coordinated PPh(2)CtriplebondCR ligands
      into a PtbondC(6)F(5) bond. Although in solution the presence of coordinated
      solvent S (S=(thf)(x)(H(2)O)(y)) in 6, 7 is suggested by NMR spectroscopy, X-ray
      diffraction analyses of different crystals of the mixed complex [Pt(C(6)F(5))mu
      [C(tBu)doublebondC(PPh(2))C(PPh(2))doublebondC(Tol)(C(6)F(5))]Pt(C(6)F(5))(2)] 9
      unequivocally establish that in the solid state the steric crowding of the new
      diphenylbutadienyl ligand formed stabilizes an unusual coordinatively unsaturated
      T-shaped 3-coordinated platinum(II) center. Structure determinations of the
      mononuclear precursors cis-[Pt(C(6)F(5))(2)(PPh(2)CtriplebondCR)(2)] (R=Ph, tBu,
      Tol) have been carried out to evaluate the factors affecting the insertion
      processes. The reactions of the platinum complexes 6 towards neutral ligands
      (L=CO, py, PPh(2)H, CNtBu) in a 1:1 molar ratio afford related diplatinum
      derivatives 10-13, whereas treatment with CNtBu (1:2 molar ratio) or 2,2'-bipy
      (1:1 molar ratio) results in the opening of the chelating ring to give cis,cis
      [Pt(C(6)F(5))(L)(2)mu-[1-kappaC(1):2-kappaPP'
      C(R)doublebondC(PPh(2))C(PPh(2))doublebondC(R)(C(6)F(5))]Pt(C(6)F(5))(2)] (14,
      15). The unsaturated or solvento complexes are unstable in solution evolving
      firstly, through an unexpected formal 4-1 R (Ph, Tol) migration, to the
      intermediate diphosphanylbutadienyl isomer derivatives [Pt(C(6)F(5))(S)mu
      [C(C(6)F(5))doublebondC(PPh(2))C(PPh(2))doublebondC(R)(2)]M(C(6)F(5))(2)] (16,
      18) (X-ray, R=Ph, M=Pt) and, finally, to 1-pentafluorophenyl-2,3
      bis(diphenylphosphanyl)naphthalene mononuclear complexes (17, 19) by annulation
      of a phenyl or tolyl group.

PMID- 12203298
TI  - Synthesis and characterization of upper and lower rim functionalized
      [6]cavitands.
AB  - A [6]cavitand has been selectively derivatized on both the lower and upper rims.
      On the lower rim, two out of six potential sites were oxidized to produce a 1,4
      substituted [6]cavitand bisketone, which was converted to a corresponding diol as
      well as a bisacetate [6]cavitand. The crystal structures of the bisketone and the
      diol were solved. On the upper rim, all six ArCH(3) groups were selectively
      brominated to ArCH(2)Br groups to produce the hexabromomethyl [6]cavitand, which
      was converted to the corresponding hexabenzylthiol and hexabenzylthioacetate
      [6]cavitands. The conformational properties of all compounds are discussed.

PMID- 12203299
TI  - Increasing the ketone selectivity of the cobalt-catalyzed radical chain oxidation
      of cyclohexane.
AB  - A variety of heterogeneous catalysts for the radical chain oxidation of
      cyclohexane has been prepared by immobilization of the well-defined cobalt
      acetate oligomers [py(3)Co(3)(mu(3)-O)(OH)(O(2)CCH(3))(5)](PF(6)) (1) and
      [py(4)Co(2)(OH)(2)(O(2)CCH(3))(3)](PF(6)) (2) on carboxy-modified mesoporous
      silica supports A-D by carboxylate exchange. The catalytic oxidation of
      cyclohexane with tert-butyl hydroperoxide (TBHP) in the presence of these
      homogeneous and immobilized cobalt acetate complexes afforded the corresponding
      alcohol and ketone in high yield. The immobilization of 1 and 2 results in a
      significant increase of catalytic activity. TBHP acts as a radical initiator and
      as source of molecular oxygen, which is also involved in the overall oxidation
      process. The rate of cyclohexane conversion is limited by the diffusion of
      molecular oxygen, and steady-state concentrations of cyclohexanone (K, ketone)
      and cyclohexanol (A, alcohol) are established; these determine the maximum K:A
      ratio.

PMID- 12203300
TI  - Tetraaminoperylenes: their efficient synthesis and physical properties.
AB  - Trimethylsilylation of 1,8-diaminonaphthalene gave 1,8
      bis(trimethylsilylamino)naphthalene (1 a), which was in turn lithiated with two
      molar equivalents of n-butyllithium to give the tris(thf)-solvated dilithium
      diamide [1,8-[(Me(3)SiN)Li(thf)](2)C(10)H(6)](thf) (2 a). Metal exchange of 2 a
      with TlCl was carried out in two steps, via the previously characterized mixed
      metal amide [1-[(Me(3)SiN)Li(thf)(2)]-8-[(Me(3)SiN)Tl]C(10)H(6)], to give the
      dithallium diamide [1,8-[(Me(3)SiN)Tl](2)C(10)H(6)] (3 a). Thermolysis of 3 a
      cleanly gave a 1:1 mixture of the 4,9-bis(trimethylsilylamino)perylenequinone
      3,10-bis(trimethylsilylimine) (4 a) and 1 a. By this route, a whole series of
      silylated homologues of 4 a was obtained in good yields, while the same method
      proved to be inefficient for the synthesis of the alkyl-substituted analogues.
      Compound 4 a and its tert-butyldimethylsilyl derivative 4 d were reduced with
      sodium amalgam to give, after protonation, the corresponding 3,4,9,10
      tetraaminoperylenes 7 a and 7 d. Cyclic voltammetry showed two reversible,
      closely spaced reduction waves (E(red 1)=-1.39, E(red 2)=-1.59 V versus SCE)
      corresponding to this conversion. The perylenes 7 a and 7 d are thought to be the
      primary products in the reaction cascade leading to the perylene derivatives,
      involving the thermal demetalation of the thallium amides, possibly via
      Tl(II)bond;Tl(II) intermediates, first to give 7 a and its analogues. The final
      oxidation of the tetraaminoperylenes by one molar equivalent of 3 a and analogous
      thallium amides gave the quinoidal derivatives such as 4 a and 4 d, a step that
      could be studied by direct reaction of the isolated species. The UV/Vis
      absorption spectra of the 4,9-bis(silylamino)perylenequinone-3,10
      bis(silylimines) are characterized by a long-wavelength absorption band with a
      pronounced vibrational structure (lambda(max)=639 nm, lg epsilon =4.53)
      attributed to a pi*<--pi and a pi*<--n absorption band at 454 nm (lg epsilon
      4.83), along with intense absorption in the UV region. A weak red emission with a
      rather low quantum yield (Phi(fl)=0.001, lambda(max)=660 nm) is observed upon
      irradiation of a sample; the lifetime of the emission is only 66 ps. The low
      emission quantum yield is attributed to the *pi<--n transition of the amino
      perylene, which induces strong spin-orbit coupling, leading to a large triplet
      yield. The triplet state was probed by transient absorption spectroscopy and
      found to have a lifetime of 200 ns in air, and 1100 ns in argon-flushed solution.
      Treatment of 4 a with a stoichiometric amount of KF in methanol/water under phase
      transfer conditions (with the cryptand [C 222]) gave an almost quantitative yield
      of the parent compound 4,9-diaminoperylenequinone-3,10-diimine (8). Treatment of
      8 with two molar equivalents of the ruthenium complex
      [Ru(bpy)(2)(acetone)(2)](PF(6))(2), generated in situ, yielded the blue dinuclear
      ruthenium complex [(bpy)(4)Ru(2)[mu(2)-N,N':N",N"'-[[4,9-(NH(2))(2)-3,10
      (NH)(2)]C(20)H(8)]]](PF(6))(4) (9), the redox properties of which were studied by
      cyclic voltammetry. The difference in the potentials of the two one-electron
      redox steps (225 mV) indicates strong coupling of the metal centers through the
      4,9-diaminoperylenquinone-3,10-dimine bridging ligand and corresponds to a
      comproportionation constant K(c) of 6.3 x 10(3). The UV/Vis absorption spectrum
      of the mixed valent form, which is stable in air, has a characteristic
      intervalence charge-transfer (IVCT) band in the near infrared at 930 nm (lg
      epsilon =3.95), from which an electronic coupling parameter J of 760 cm(-1) could
      be estimated, placing compound 9 at the borderline between the class II and class
      III cases in the Robin-Day classification.

PMID- 12203301
TI  - Total synthesis of epothilone a through stereospecific epoxidation of the p
      methoxybenzyl ether of epothilone C.
AB  - The total synthesis of epothilone A is described by the coupling four segments 4
      7 a. Three of the segments, 4, 5 and 7 a, have only one chiral center; all other
      chiral centers were introduced by simple asymmetric catalytic reactions. The key
      steps are the ring opening of epoxide 5 with acetylide 8 for the construction of
      the C12-C13 cis double bond and a practical hydrolytic kinetic resolution (HKR)
      developed by Jacobsen group for the introduction the chiral center at C3.
      Especially, the stereospecific epoxidation of 3-O-PMB epothilone C 3 b through
      long-range effect of 3-O-PMB protecting group gave high yields of the C12-C13
      alpha-epoxide for the synthesis of target molecule.

PMID- 12203302
TI  - Synthesis, redox properties, and EPR spectroscopy of manganese(III) complexes of
      the ligand N,N-bis(2-hydroxybenzyl)-N'-2-hydroxybenzylidene-1,2-diaminoethane:
      formation of mononuclear, dinuclear, and even higher nuclearity complexes.
AB  - The synthesis and characterization of the title trisphenolate ligand are
      described. From its reaction with manganese(III) three complexes were isolated.
      The crystal structures revealed one pentacoordinate monomer and two similar
      dimers with different solvents of crystallization. In the dimers the metal ions
      are hexacoordinate and connected through bridging of two phenolates. A
      combination of electrochemistry and EPR spectroscopy showed that, in
      acetonitrile, the isolated batches were all identical and mainly monomeric,
      indicating that the mononuclear complex is in equilibrium with the dimer and
      perhaps also with complexes of higher nuclearity, as suggested by the detection
      of both the trimer and the tetramer by electrospray ionization mass spectrometry
      (ESI-MS). The successful use of the monomer batch as an epoxidation catalyst
      indicated that a high-valent manganese-oxo species can be formed, although it is
      probably short-lived. This is also suggested by EPR studies of the species formed
      by electrochemical oxidation of the complex. Upon one-electron oxidation, a
      manganese(IV) species was formed, which was at least partly converted to another
      species containing a phenoxy radical.

PMID- 12203303
TI  - Enzyme accessibility and solid supports: which molecular weight enzymes can be
      used on solid supports? An investigation using confocal Raman microscopy.
AB  - The accessibility of various solid supports (TentaGel, PEGA 1900, and beaded
      controlled pore glasses (CPGs)) to a range of enzymes was investigated. The
      different beaded materials were loaded with the peptide 4-cyanobenzamide-Gly-Pro
      Leu-Gly-Leu-Phe-Ala-Arg-OH and incubated with the enzymes MMP-12 (22 kDa),
      thermolysin (35 kDa), MMP-13 (42.5 kDa), clostridium collagenase (68 kDa), and
      NEP (90 kDa). The absence/presence of the cyano stretching frequency was measured
      by means of confocal Raman microscopy. It was found that none of the investigated
      enzymes could enter the polymer matrices of TentaGel. PEGA 1900 was compatible
      only with the two smallest enzymes, while beaded CPG was successful even with NEP
      (90 kDa), proving its superiority over other materials in terms of bio
      compatibility.

PMID- 12203304
TI  - Neodymium alkoxides: synthesis, characterization and their combinations with
      dialkylmagnesiums as unique systems for polymerization and block copolymerization
      of ethylene and methyl methacrylate.
AB  - The synthesis and characterization (NMR and X-ray) of a variety of neodymium
      alkoxides derived from simple and functionalized tertiary monoalcohols, and their
      application as inorganic precursors in combination with dialkylmagnesium reagents
      for ethylene and methyl methacrylate (MMA) (co)polymerization have been
      investigated. Salt metathesis reactions between NdCl(3) and sodium alkoxides in
      THF led to the formation of trinuclear complexes [Nd(3)(mu(3)-OR)(2)(mu(2)
      OR)(3)(OR)(4)(thf)(2)] with R=tBu (1), tAm (2), while aggregate structure
      [Nd(12)(OtAm)(26)(HOtAm)(2)Cl(11)Na].(OEt(2))(2) (3) was obtained when the
      synthesis was performed in Et(2)O. [Nd(3)(mu(3)-OtBu)(2)(mu(2)
      OtBu)(3)(OtBu)(4)(HOtBu)(2)] (4), prepared by aminolysis of Nd[N(SiMe(3))(2)](3)
      in hexane, slowly decomposed in toluene into oxo complex [Nd(5)(mu(5)-O)(mu(3)
      OtBu)(4)(mu(2)-OtBu)(4)(OtBu)(5)] (5). Finally, the dimer [Nd(2)(mu(2),eta(2)
      OR)(2)(eta(2)-OR)(2)(eta(1)-OR)(2)] (OR=OCMe(2)CH(2)CH(2)OMe) (6) was synthesised
      by aminolysis reaction from the corresponding gamma-donor-functionalized alcohol.
      Some of these neodymium alkoxides, in particular homoleptic complex 1, when
      associated in situ to one equivalent of a dialkylmagnesium, allow the formation
      of an active catalyst for ethylene polymerization. Under mild conditions (0
      degrees C, 1 bar), the latter catalyst system exhibited a moderate activity (5-10
      kg mol(-1) h(-1) bar(-1)). Effective transfer reactions were observed in the
      presence of H(2) or PhSiH(3) and renewal/improvement of activity occurred upon
      extra addition of dialkylmagnesium. The most outstanding feature of this
      catalytic system lies in the precipitation of the active "Nd-polyethylenyl"
      species during the ethylene polymerization course as solid S which could be
      isolated. This heterogeneity was turned to good account, enabling to achieve
      heterogeneous solid-gas ethylene polymerization and to prepare diblock PE-PMMA
      copolymers with high diblock efficiency and high molecular weights (M(n) > 200
      000). A catalytic cycle for this unique system is proposed based on the isolation
      of a transmetallation product (7) from a neodymium alkoxide/dialkylmagnesium
      combination and NMR studies of the latter.

PMID- 12203305
TI  - Mono- and disubstituted N,N-dialkylcyclopropylamines from dialkylformamides via
      ligand-exchanged titanium-alkene complexes.
AB  - Dibenzylformamide was treated with cyclohexylmagnesium bromide in the presence of
      either titanium tetraisopropoxide or methyltitanium triisopropoxide and a variety
      of cyclic and acyclic alkenes and alkadienes to give new mono- and disubstituted
      as well as bicyclic dialkylcyclopropylamines (Tables 1-3) in yields ranging from
      18 to 90 % (in most cases around 55 %). 3-Benzyl-6-(N,N-dibenzylamino)-3
      azabicyclo[3.1.0]hexane (10 a) and the orthogonally bisprotected 3-tert
      butoxycarbonyl-6-(N,N-dibenzyl)-3-azabicyclo[3.1.0]hexane (10 d) as well as the
      analogous 6-(N,N-dibenzylamino)bicyclo[3.1.0]hexane (12) were obtained as pure
      exo diastereomers in particularly high yields (87, 90, and 88 %, respectively)
      from N-benzylpyrroline (15 a), N-Boc-pyrroline (15 d; Boc=tert-butyloxycarbonyl)
      and cyclopentene (19). 1,3-Butadiene (52) and substituted 1,3-butadienes were
      also aminocyclopropanated quite well to give 2-ethenylcyclopropylamines in good
      yields (51-64 %). Except for alkenyl- and aryl-substituted compounds, N,N
      dibenzylcyclopropylamines can be debenzylated by catalytic hydrogenation to the
      primary cyclopropylamines as demonstrated for 10 a and 10 d to yield the fully
      deprotected 10 e (93 %) and mono-Boc-protected 10 f (98 %), respectively. The
      latter are interesting templates for combinatorial syntheses of libraries of
      small molecules with a well defined distance of 4.3 A between two nitrogen atoms.

PMID- 12203306
TI  - Synthesis of B/Ga and B/In heteronuclear bidentate Lewis acids: formation of
      intramolecular pi-arene-gallium(III) and -indium(III) complexes.
AB  - Reaction of 1,8-dilithionaphthalene x TMEDA (TMEDA=tetramethylethylenediamine)
      with dimesitylboron fluoride in diethyl ether followed by treatment with THF
      affords the Li(THF)(4) salt of dimesityl-1,8-naphthalenediylborate (1). Compound
      1-Li(THF)(4) undergoes a ring-opening reaction with trimethyltin chloride to
      afford high yields of 1-(dimesitylboron)-8-(trimethyltin)naphthalenediyl (2), a
      compound in which a boryl and a stannyl moiety coexist at the peri positions of a
      naphthalene core. Compound 2 has been characterized by multinuclear NMR
      spectroscopy, elemental analysis, and X-ray single-crystal analysis which reveal
      the existence of a sterically crowded structure. Compound 2 is a useful starting
      material for the synthesis of other heteronuclear naphthalene derivatives. Thus,
      the transmetalation reaction of 2 with GaCl(3) or InCl(3) in THF results in high
      yields of 1-(dichlorogallium)-8-(dimesitylboron)naphthalenediyl (3) and 1
      (dichloroindium)-8-(dimesitylboron)naphthalenediyl (4), respectively. These
      unprecedented boron/gallium and boron/indium heteronuclear bidentate Lewis acids
      have been characterized by multinuclear NMR spectroscopy, elemental analysis, and
      X-ray single-crystal analysis. Owing to the presence of a short contact between
      the ipso-carbon atom of a mesityl group and the heavy Group 13 element
      (C(ipso)bondGa 2.279(4) A for 3, C(ipso)bondIn 2.442(6) A for 4), compounds 3 and
      4 are best described as intramolecular pi-arene complexes and are the first
      examples of such complexes. As shown by (1)H and (13)C NMR spectroscopy, this pi
      interaction subsists in solution.

PMID- 12203307
TI  - Fluorescence of dyes adsorbed on highly organized, nanostructured gold surfaces.
AB  - It is shown that fluorescent dyes can be adsorbed selectively on gold
      nanoparticles which are immobilized on a glass substrate and that the
      fluorescence originating from the adsorbed dyes exhibits significantly less
      quenching when compared to dyes adsorbed on bulk gold. Self-assembled monolayers
      of lissamine sulfide molecules have been studied both on bulk gold and on glass
      surfaces bearing gold nanoparticles. Gold nanoparticles have been arranged in
      ordered, two-dimensional patterns, with periodicity in the microm range and used
      as substrate for the fluorescent dyes. Optical resolution of the fluorescence
      originating from the pattern has been achieved with laser-scanning confocal
      microscopy.

PMID- 12203310
TI  - New insights in the search for chiral Bronsted bases.
AB  - The concept of using chiral bases in asymmetric synthesis appeared with the
      emergence of the chemistry of chiral lithium amides. In recent years, new classes
      of chiral bases, such as chiral magnesium bisamides and chiral alkali alkoxides
      have proven to be highly efficient and easy to handle. This paper highlights
      recent advances and new concepts in the chemistry of this second generation of
      chiral bases.

PMID- 12203311
TI  - Application of complex macromolecular architectures for advanced microelectronic
      materials.
AB  - The distinctive features of well-defined, three-dimensional macromolecules with
      topologies designed to enhance solubility and amplify end-group functionality
      facilitated nanophase morphologies in mixtures with organosilicates and
      ultimately nanoporous organosilicate networks. Novel macromolecular architectures
      including dendritic and star-shaped polymers and organic nanoparticles were
      prepared by a modular approach from several libraries of building blocks
      including various generations of dendritic initiators and dendrons, selectively
      placed to amplify functionality and/or arm number, coupled with living
      polymerization techniques. Mixtures of an organosilicate and the macromolecular
      template were deposited, cured, and the phase separation of the organic
      component, organized the vitrifying organosilicate into nanostructures. Removal
      of the sacrificial macromolecular template, also denoted as porogen, by
      thermolysis, yielded the desired nanoporous organosilicate, and the size scale of
      phase separation was strongly dependent on the chain topology. These materials
      were designed for use as interlayer, ultra-low dielectric insulators for on-chip
      applications with dielectric constant values as low as 1.5. The porogen design,
      chemistry and role of polymer architecture on hybrid and pore morphology will be
      emphasized.

PMID- 12203312
TI  - Vine-twining polymerization: amylose twines around polyethers to form amylose
      polyether inclusion complexes.
AB  - In this paper, we describe a new polymerization manner termed as "vine-twining
      polymerization" to produce amylose-polymer inclusion complexes. The
      polymerization was achieved by an enzymatic polymerization of alpha-D-glucose-1
      phosphate monomer catalyzed by phosphorylase in the presence of polyTHF as a
      guest polymer. The structure of the product was determined by X-ray powder
      diffraction and (1)H NMR measurements to be the inclusion complex. The formation
      process of the inclusion complexes during the polymerization was also evaluated.
      Furthermore, the formation of the inclusion complexes by this polymerization
      method by using polyTHFs with various M(n)s and end groups, as well as other
      polyethers as the guest polymers, was examined.

PMID- 12203313
TI  - A strategy for the stereoselective synthesis of unsymmetric atropisomeric
      ligands: preparation of NAPhePHOS, a new biaryl diphosphine.
AB  - MeO-NAPhePHOS represents the first example of a new series of atropisomeric
      diphosphines bearing heterotopic biaryl moieties. The key step of its synthesis
      is the diastereoselective, intramolecular, Cu(I)-promoted coupling of 1
      iodonaphthol and 2-iodo-3-methoxyphenol connected by a chiral tether. (R,R)-2,4
      Pentanediol is used as the chiral auxiliary in this highly selective reaction
      that leads to a single enantiomer of the title diphosphine. In the Ru-promoted
      hydrogenations of carbonyl derivatives, NAPhePHOS affords enantioselectivity
      levels fully comparable to those of the C(2)-symmetrical analogues, BINAP and MeO
      BIPHEP respectively, thus showing that the lack of C(2) symmetry is not
      detrimental to the catalytic properties of atropisomeric ligands in these
      hydrogenation reactions.

PMID- 12203314
TI  - Photoinduced formation of a cryptand from a coronand: an unexpected switch in
      cation binding affinity.
AB  - Aza-crown ethers 2 and 3 with anthracene-containing pendant arms have been
      synthesised and characterised. Both compounds bind Group 1 metal cations in
      solution, forming complexes of 1:1 stoichiometry. The properties of compound 2
      and its complexes have been studied by a range of techniques, including NMR, UV
      and fluorescence spectroscopy and X-ray crystallography. The pendant arms can
      adopt either a cis or a trans geometry, the cis geometry favoured with larger
      cations. The geometry of the complex affects the fluorescence properties of the
      system, with larger cations giving higher excimer/monomer ratios. Upon
      irradiation at lambda>300 nm, coronand 2 forms the cryptand 5 through a
      reversible intramolecular [4pi+4pi] cycloaddition reaction. The rates of the
      forward and reverse reactions of this photochromic process are cation dependent;
      in particular the rate of the thermal reverse reaction is decreased by smaller
      cations and increased by larger cations, especially Rb(+). The metal binding
      constants in methanol for 2 and 5 have been determined, revealing that the
      cryptand 5 binds Na(+) and Rb(+) more weakly than crown ether 2 by over two
      orders of magnitude.

PMID- 12203315
TI  - New diphosphine ligands containing ethyleneglycol and amino alcohol spacers for
      the rhodium-catalyzed carbonylation of methanol.
AB  - The new diphosphine ligands Ph(2)PC(6)H(4)C(O)X(CH(2))(2)OC(O)C(6)H(4)PPh(2) (1:
      X=NH; 2: X=NPh; 3: X=O) and
      Ph(2)PC(6)H(4)C(O)O(CH(2))(2)O(CH(2))(2)OC(O)C(6)H(4)PPh(2) (5) as well as the
      monophosphine ligand Ph(2)PC(6)H(4)C(O)X(CH(2))(2)OH (4) have been prepared from
      2-diphenylphosphinobenzoic acid and the corresponding amino alcohols or diols.
      Coordination of the diphosphine ligands to rhodium, iridium, and platinum
      resulted in the formation of the square-planar complexes [(Pbond;P)Rh(CO)Cl] (6:
      Pbond;P=1; 7: Pbond;P=2; 8: Pbond;P=3), [(Pbond;P)Rh(CO)Cl](2) (9: Pbond;P=5),
      [(P-P)Ir(cod)Cl] (10: Pbond;P=1; 11: Pbond;P=2; 12: Pbond;P=3),
      [(Pbond;P)Ir(CO)Cl] (13: Pbond;P=1; 14: Pbond;P=2; 15: Pbond;P=3), and
      [(Pbond;P)PtI(2)] (18: Pbond;P=2). In all complexes, the diphosphine ligands are
      trans coordinated to the metal center, thanks to the large spacer groups, which
      allow the two phosphorus atoms to occupy opposite positions in the square-planar
      coordination geometry. The trans coordination is demonstrated unambiguously by
      the single-crystal X-ray structure analysis of complex 18. In the case of the
      diphosphine ligand 5, the spacer group is so large that dinuclear complexes with
      ligand 5 in bridging positions are formed, maintaining the trans coordination of
      the P atoms on each metal center, as shown by the crystal structure analysis of
      9. The monophosphine ligand 4 reacts with [[Ir(cod)Cl](2)] (cod=cyclooctadiene)
      to give the simple derivative [(4)Ir(cod)Cl] (16) which is converted into the
      carbonyl complex [(4)Ir(CO)(2)Cl] (17) with carbon monoxide. The crystal
      structure analysis of 16 also reveals a square-planar coordination geometry in
      which the phosphine ligand occupies a position cis with respect to the chloro
      ligand. The diphosphine ligands 1, 2, 3, and 5 have been tested as cocatalysts in
      combination with the catalyst precursors [[Rh(CO)(2)Cl](2)] and [[Ir(cod)Cl](2)]
      or [H(2)IrCl(6)] for the carbonylation of methanol at 170 degrees C and 22 bar
      CO. The best results (TON 800 after 15 min) are obtained for the combination
      2/[[Rh(CO)(2)Cl](2)]. After the catalytic reaction, complex 7 is identified in
      the reaction mixture and can be isolated; it is active for further runs without
      loss of catalytic activity.

PMID- 12203316
TI  - Synthesis, optical properties, and aggregation behavior of a triad system based
      on perylene and oligo(p-phenylene vinylene) units.
AB  - A donor-acceptor-donor triad molecule with a perylene bisimide derivative as
      electron acceptor, and an oligo(p-phenylene vinylene) (OPV) derivative as
      electron donor was synthesized (OPV-PERY-OPV). The structure of the triad was
      characterized by (1)H and (13)C NMR spectroscopy, size-exclusion chromatography
      (SEC), and MALDI-TOF spectrometry. Absorbance spectra and CD spectroscopic
      measurements of the triad molecule indicated the formation of aggregates in
      solvents such as toluene, chloroform, and tetrachloroethane, whereas it was
      present in the molecularly dissolved state in THF. The (1)H NMR spectra of the
      molecule in chloroform had, unexpectedly, four doublet peaks for the perylene
      protons, instead of the two doublets that is generally seen in N,N'-substituted
      perylene molecules. To understand the aggregation behavior and the splitting of
      the signals in the (1)H NMR spectra, a simple model compound was synthesized, in
      which the OPV units were replaced by phenyl groups (Ph-PERY-Ph). (1)H NMR spectra
      in CDCl(3) and tetrachloroethane again had four doublet peaks for the perylene
      protons, whereas in THF the perylene protons gave only a single peak. NOE and
      COSY spectroscopy were used to assign the peaks to their corresponding perylene
      protons. UV/Vis and CD spectroscopic measurements indicated that, similar to the
      OPV-PERY-OPV triad molecule, the model compound Ph-PERY-Ph was also present in
      the aggregated form in solvents such as toluene, chloroform, and
      tetrachloroethane, and in the molecularly dissolved state in THF. IR measurements
      of the model molecule in the first set of solvents indicated carbamate bond
      (bond;OCObond;NHbond;)-induced intermolecular hydrogen bonding, whereas in THF,
      the molecule was mostly present in the free form. CPK models with a dimeric
      structure, in which two perylene molecules are held together by intermolecular
      hydrogen bonding with the perylene core shifted slightly with respect to one
      another, could account for the optical properties and the observation of the four
      different peaks in the (1)H NMR spectra in polar solvent. Temperature-dependent
      (1)H NMR spectroscopic, UV/Vis, and CD measurements indicated that the transition
      from the aggregated to the molecularly dissolved state took place at higher
      temperatures. The electrochemical studies indicated that OPV-PERY-OPV was both p-
      and n-dopable, whereas Ph-PERY-Ph was only n-dopable. Cyclic voltammetry
      measurements of Ph-PERY-Ph in THF had two reduction peaks corresponding to the
      reduction of the perylene core to the monoanion and dianion, respectively. In
      dichloromethane, however, an additional reduction peak at lower potential was
      observed. This new reduction peak might arise from the hydrogen-bonded species.

PMID- 12203317
TI  - Synthesis and membrane binding properties of a lipopeptide fragment from
      influenza virus a hemagglutinin.
AB  - Hemagglutinin from influenza virus A is a S-palmitoylated lipoglycoprotein in
      which the lipid groups are thought to influence the interaction between cell
      membrane and capsid during budding of viral offspring as well as fusion processes
      of the viral membrane with the endosome after entry of the viral particle into
      the cell. The paper describes the development of a method for the synthesis of
      characteristic lipidated hemagglutinin derived peptides which additionally carry
      the fluorescent 7-nitrobenz-2oxa-1,3-diazole (NBD) group. To achieve this goal
      the enzyme-sensitive para-phenylacetoxybenzyloxycarbonyl (PAOB) ester was
      developed. It is cleaved from the peptides and lipidated peptides under very mild
      conditions and with complete selectivity by treatment with the enzyme penicillin
      G acylase; this results in the formation of a phenolate. This intermediate
      spontaneously undergoes fragmentation thereby releasing the desired carboxylates.
      The combined use of this enzyme-labile fragmenting ester with the acid-labile Boc
      group, the Pd(0)-sensitive allyl ester and the corresponding Aloc urethane gave
      access to a mono-S-palmitoylated and a doubly S-palmitoylated NBD-labelled
      hemagglutinin peptide. The binding of these lipopeptides to model membranes was
      analyzed in a biophysical setup monitoring the transfer of fluorescent-labelled
      lipopeptide from vesicles containing the non-exchangeable fluorescence quencher
      Rho-DHPE to quencher-free vesicles. The experiments demonstrate that one lipid
      group is not sufficient for quasi-irreversible membrane insertion of lipidated
      peptides. This is, however, achieved by introduction of the bis-palmitoyl anchor.
      The intervesicle transfer always implies release of peptides localized at the
      outer face of the vesicles into solution followed by diffusion to and insertion
      into acceptor vesicles. For peptides bound at the inner face of the vesicle
      membrane, however, an additional flip-flop diffusion to the outer face has to
      occur beforehand. The kinetics of these processes were estimated by fast chemical
      quench of the outside fluorophores by sodium dithionite.

PMID- 12203318
TI  - Templating and selection in the formation of macrocycles containing [[P(micro
      NtBu)(2)](micro-NH)](n) frameworks: observation of halide ion coordination.
AB  - Amination of [ClP(micro-NtBu)](2) (1) using NH(3) in THF gives the
      cyclophospha(III)zane dimer [H(2)NP(micro-NtBu)](2) (2), in good yield. (31)P NMR
      spectroscopic studies of the reaction of 1 with 2 in THF/Et(3)N show that almost
      quantitative formation of the cyclic tetramer [[P(micro-NtBu)](2)(micro-NH)](4)
      (3) occurs. The remarkable selectivity of this reaction can (in part) be
      attributed to pre-organisation of 1 and 2, which prefer cis arrangements in the
      solid state and solution. The macrocycle 3 can be isolated in yields of 58-67 %
      using various reaction scales. The isolation of the major by-product of the
      reaction (ca. 0.5-1 % of samples of 3), the pentameric, host-guest complex
      [[P(micro-NtBu)(2)](2)(micro-NH)](5)(HCl).2 THF] (4.2 THF), gives a strong
      indication of the mechanism involved. In situ (31)P NMR spectroscopic studies
      support a stepwise condensation mechanism in which Cl(-) ions play an important
      role in templating and selection of 3 and 4. Amplification of the pentameric
      arrangement occurs in the presence of excess LiX (X=Cl, Br, I). In addition, the
      cyclisation reaction is solvent- and anion-dependent. The X-ray structures of 2
      and 4.2 THF are reported.

PMID- 12203319
TI  - Approaching the gas-phase structures of [AgS8]+ and [AgS16]+ in the solid state.
AB  - Upon treating elemental sulfur with [AgSbF(6)], [AgAl(hfip)(4)], [AgAl(pftb)(4)]
      (hfip=OCH(CF(3))(2), pftb =OC(CF(3))(3)) the compounds [Ag(S(8))(2)][SbF(6)] (1),
      [AgS(8)][Al(hfip)(4)] (2), and [Ag(S(8))(2)](+)[[Al(pftb)(4)](-) (3) formed in
      SO(2) (1), CS(2) (2), or CH(2)Cl(2) (3). Compounds 1-3 were characterized by
      single-crystal X-ray structure determinations: 1 by Raman spectroscopy, 2 and 3
      by solution NMR spectroscopy and elemental analyses. Single crystals of
      [Ag(S(8))(2)](+)[Sb(OTeF(5))(6)](-) 4 were obtained from a disproportionation
      reaction and only characterized by X-ray crystal structure analysis. The Ag(+)
      ion in 1 coordinates two monodentate SbF(6) (-) anions and two bidentate S(8)
      rings in the 1,3-position. Compound 2 contains an almost C(4v)-symmetric
      [AgS(8)](+) moiety; this is the first example of an eta(4)-coordinated S(8) ring
      (d(Agbond;S)=2.84-3.00 A). Compounds 3 and 4, with the least basic anions,
      contain undistorted, approximately centrosymmetric Ag(eta(4)-S(8))(2) (+) cations
      with less symmetric eta(4)-coordinated S(8) rings (d(Agbond;S)=2.68-3.35 A). The
      thermochemical radius and volume of the undistorted Ag(S(8))(2) (+) cation was
      deduced as r(therm)(Ag(S(8))(2) (+))=3.378+ 0.076/-0.120 A and
      V(therm)(Ag(S(8))(2) (+))=417+4/-6 A(3). AgS(8) (+) and several isomers of the
      Ag(S(8))(2) (+) cation were optimized at the BP86, B3LYP, and MP2 levels by using
      the SVP and TZVPP basis sets. An analysis of the calculated geometries showed the
      MP2/TZVPP level to give geometries closest to the experimental data. Neither BP86
      nor B3LYP reproduced the longer weak dispersive Agbond;S interactions in
      Ag(eta(4)-S(8))(2) (+) but led to Ag(eta(3)-S(8))(2) (+) geometries. With the
      most accurate MP2/TZVPP level, the enthalpies of formation of the gaseous
      [AgS(8)](+) and [Ag(S(8))(2)](+) cations were established as
      Delta(f)H(298)([Ag(S(8))(2)](+), g)=856 kJ mol(-1) and
      Delta(f)H(298)([AgS(8)](+), g)=902 kJ mol(-1). It is shown that the [AgS(8)](+)
      moiety in 2 and the [AgS(8)](2) (+) cations in 3 and 4 are the best approximation
      of these ions, which were earlier observed by MS methods. Both cations reside in
      shallow potential-energy wells where larger structural changes only lead to small
      increases in the overall energy. It is shown that the covalent Agbond;S bonding
      contributions in both cations may be described by two components: i) the
      interaction of the spherical empty Ag 5s(0) acceptor orbital with the filled S
      3p(2) lone-pair donor orbitals and ii) the interaction of the empty Ag 5p(0)
      acceptor orbitals with the filled S 3p(2) lone-pair donor orbitals. This latter
      contribution is responsible for the observed low symmetry of the centrosymmetric
      Ag(eta(4)-S(8))(2) (+) cation. The positive charge transferred from the Ag(+) ion
      in 1-4 to the coordinated sulfur atoms is delocalized over all the atoms in the
      S(8) ring by multiple 3p(2)-->3sigma* interactions that result in a small long
      short-long-short Sbond;S bond-length alternation starting from S1 with the
      shortest Agbond;S length. The driving force for all these weak bonding
      interactions is positive charge delocalization from the formally fully localized
      charge of the Ag(+) ion.

PMID- 12203320
TI  - Magnetic properties and aromaticity of o-, m-, and p-benzyne.
AB  - The relative aromaticities of the three singlet benzyne isomers, 1,2-, 1,3-, and
      1,4-didehydrobenzenes have been evaluated with a series of aromaticity
      indicators, including magnetic susceptibility anisotropies and exaltations,
      nucleus-independent chemical shifts (NICS), and aromatic stabilization energies
      (all evaluated at the DFT level), as well as valence-bond Pauling resonance
      energies. Most of the criteria point to the o-benzyne<m-benzyne<p-benzyne
      aromaticity order, whereas the relative aromaticity of each isomer with respect
      to benzene depends on the aromaticity criterion. An additional aromaticity
      evaluation involved the transition state of the Bergman cyclization of (Z)-hexa
      1,5-diyn-3-ene which yields p-benzyne. Dissected NICS calculations reveal an
      aromatic transition state with a larger total NICS but a smaller NICS(pi)
      component and thus lower aromaticity than benzene.

PMID- 12203321
TI  - Enantioselective vicinal bis-acylation of olefins.
AB  - A two-step sequence for the asymmetric vicinal acylation of olefins by a [2+2+1]
      strategy is reported. The key reaction is a [2+2] cycloaddition of an olefin to a
      chiral keteniminium salt derived from N-tosylsarcosinamide. This is followed by a
      regioselective Baeyer-Villiger oxidation of the resulting cyclobutanone to yield
      a lactol derivative that is equivalent to the product of addition of a carboxyl
      and a carbonyl group to the olefin. N-Tosylsarcosinamides derived from prolinol
      methyl ether and 2,5-dimethylpyrrolidine gave the best yields and
      diastereoselectivities. Five- and six-membered cycloolefins only gave cis
      products as expected. With seven- and eight-membered rings and cis 1,2
      disubstituted acyclic olefins, partial or complete epimerisation of the cis to
      the trans adducts was observed. Facial selectivities were generally good except
      for terminal olefins. The oxidation step proceeded in high yields to give
      crystalline compounds which could usually be obtained in enantiopure form by
      simple recrystallisation.

PMID- 12203322
TI  - The origin of endo stereoselectivity in the hetero-Diels-Alder reactions of
      aldehydes with ortho-xylylenes: CH-pi, pi-pi, and steric effects on
      stereoselectivity.
AB  - Theoretical studies of stereoselectivity have been carried out with B3LYP and MP2
      calculations. The high endo selectivity of hetero-Diels-Alder reactions of ortho
      xylylenes with acetaldehydes is shown to result from attractive CH-pi
      interactions between alkyl groups of the aldehyde and the aromatic ring in the
      transition states of the reaction. For the hetero-Diels-Alder reactions of ortho
      xylylenes with benzaldehyde, the stereoselectivity is shown to be mainly governed
      by the attractive pi-pi interactions between the phenyl rings of the benzaldehyde
      and the ortho-xylylene. MP2 calculations are necessary to reproduce the
      stabilizing dispersion interactions.

PMID- 12203323
TI  - Fine-tuned characterization at the solid/solution interface of organotin
      compounds grafted onto cross-linked polystyrene by using high-resolution MAS NMR
      spectroscopy.
AB  - The structural characterization of organotin compounds that are grafted onto
      insoluble cross-linked polymers has necessarily been limited to elemental
      analysis, infrared spectroscopy, and in a few instances, solid-state NMR
      spectroscopy. This important bottleneck in the development of such grafted
      systems has been addressed by using high-resolution magic angle spinning (hr-MAS)
      NMR spectroscopy. The great potential of this technique is demonstrated through
      the structural characterization of diphenylbutyl-(3,4) and dichlorobutylstannanes
      (5,6), grafted onto divinylbenzene cross-linked polystyrene by means of a
      suitable linker (1, 2). First, conditions suitable for the application of hr-MAS
      NMR spectroscopy were identified by characterizing the (1)H resonance line widths
      of the grafted organotin moiety following swelling of the functionalized beads in
      eight representative solvents. The presence of clearly identifiable tin coupling
      patterns in both the 1D (13)C and 2D (1)H-(13)C HSQC spectra, and the
      incorporation of (119)Sn chemical shift and connectivity information from hr-MAS
      1D (119)Sn and 2D (1)H-(119)Sn HMQC spectra, provide an unprecedented level of
      characterization of grafted organotins directly at the solid/liquid interface. In
      addition, the use of hr-MAS (119)Sn NMR for reaction monitoring, impurity
      detection, and quantification and assessment of the extent of coordination
      reveals its promise as a novel tool for the investigation of polymer-grafted
      organotin compounds. The approach described here should be sufficiently general
      for extension to a variety of other nuclei of interest in polymer-supported
      organometallic chemistry.

PMID- 12203324
TI  - Unequivocal synthetic pathway to heterodinuclear (4f,4f') complexes: magnetic
      study of relevant (Ln(III), Gd(III)) and (Gd(III), Ln(III)) complexes.
AB  - The tripodal ligand tris[4-(2-hydroxy-3-methoxyphenyl)-3-aza-3-buten]amine
      (LH(3)) is capable of coordinating to two different lanthanide ions to give
      complexes formulated as [LLnLn'(NO(3))(3)].x H(2)O. The stepwise synthetic
      procedure consists of introducing first a Ln(III) ion in the inner N(4)O(3)
      coordination site. The isolated neutral complex LLn is then allowed to react with
      a second and different Ln' ion that occupies the outer O(6) site, thus yielding a
      [LLnLn'(NO(3))(3)].x H(2)O complex. A FAB(+) study has confirmed the existence of
      (Ln, Ln') entities as genuine, when the Ln' ion in the outer site has a larger
      ionic radius than the Ln ion in the inner site. The qualitative magnetic study of
      the (Gd, Ln) and (Ln, Gd) complexes, based on the comparison of the magnetic
      properties of (Gd, Ln) (or (Ln, Gd)) pairs and (Y, Ln) (or (Ln, La)) pairs, is
      very informative. Indeed, these former complexes are governed by the thermal
      population of the Ln(III) Stark levels and the Ln-Gd interaction, while the
      latter are influenced by the thermal population of the Ln(III) Stark levels. We
      have been able to show that a ferromagnetic interaction exists at low temperature
      in the (Gd, Nd), (Gd, Ce), and (Yb, Gd) complexes. In contrast, an
      antiferromagnetic interaction occurs in the (Dy, Gd) and (Er, Gd) complexes.
      Although we cannot give a quantitative value to these interactions, we can affirm
      that their magnitudes are weak since they are only perceptible at very low
      temperature.

PMID- 12203325
TI  - Helical self-organization and hierarchical self-assembly of an oligoheterocyclic
      pyridine-pyridazine strand into extended supramolecular fibers.
AB  - The synthesis and characterization of an alternating pyridine-pyridazine strand
      comprising thirteen heterocycles are described. Spontaneous folding into a
      helical secondary structure is based on a general molecular self-organization
      process enforced by the conformational information encoded within the primary
      structure of the molecular strand itself. Conformational control based on
      heterocyclic "helicity codons" illustrates a strategy for designing folding
      properties into synthetic oligomers (foldamers). Strong intermolecular
      interactions of the highly ordered lock-washer subunits of compound 3 results in
      hierarchical supramolecular self-assembly into protofibrils and fibrils. Compound
      3 also forms mechanically stable two-dimensional Langmuir-Blodgett and cast thin
      films.

PMID- 12203326
TI  - Self-assembly, characterisation, and crystal structure of multinuclear metal
      complexes of the [2 x 3] and [3 x 3] grid-type.
AB  - The self-assembly of new multimetallic complexes of grid-type architecture is
      described. The binding of a set of tris-terdentate ligands, 1 a-1 d, based on
      terpyridine-like subunits, with different octahedrally coordinated metal ions
      leads to the formation of species whose structure depends strongly on the ligand,
      the metal ion, the counterion, the solvent, and the reaction conditions. Under
      suitable conditions, the [3 x 3] grid was obtained from the reaction of ligand 1
      a with zinc tetrafluoroborate and from ligand 1 b with mercury triflate. The
      other ligands led to the formation of mainly one compound of composition
      [M(6)L(5)](12+), which has the structure of an incomplete [2 x 3] grid. The
      crystal structure of such a [2 x 3] grid, [Co(6)(1 d)(5)](12+), has been
      determined. In this complex, the three central pyrimidine-pyridine-pyrimidine non
      coordinating sites adopt transoid NCbond;CN conformations. The much less stable
      cisoid conformations, the "pinching" of the coordination sites in the complex,
      the weaker donor strength of the central binding site, and the steric demand of
      the substituents are all factors contributing to the reluctance to produce the [3
      x 3] structure. A subtle interplay between the nature of the metal, the steric
      demand of the ligand, the reaction conditions, and the type of counterion
      determine the product of self-assembly. The results obtained show that by tuning
      the parameters, complexes containing six or nine octahedrally coordinated metal
      ions in a well-defined grid-type arrangement are accessible. Both types of
      arrays, [2 x 3] and [3 x 3 ], are of interest as self-assembled inorganic
      architectures of well-defined structure and nuclearity that may be suitable
      prototypes for selective information storage media.

PMID- 12203327
TI  - Optically and thermally induced electron transfer pathways in hexakis[4-(N,N
      diarylamino)phenyl]benzene derivatives.
AB  - The optically and thermally induced electron transfer pathways of highly
      symmetrical (D(3)) hexaarylbenzene systems with six triarylamine redox sites have
      been investigated. Owing to slightly different local redox potentials, the
      radical trication could be selectively generated by electrochemical methods. This
      trication shows a strong intervalence charge-transfer band in the near infrared
      (NIR) that was measured by spectroelectrochemistry and analysed using multi
      dimensional Mulliken-Hush theory. Quantum chemical AM1 CI calculations indicate
      that there is no optically induced concerted three-electron transfer that
      transforms the ground state into a state in which all three positively charged
      triarylamine moieties change place with their neutral neighbours. The potential
      energy surface of the ground state was constructed by using quadratic potentials.
      From this potential surface it is apparent that there is also no thermally
      allowed concerted three-electron transfer pathway. Instead, three consecutive one
      electron transfer steps are necessary for this process.

PMID- 12203328
TI  - Lipophilicity and solvation of anionic drugs.
AB  - This paper first gives a brief review of the main techniques used to measure the
      lipophilicity of neutral and ionic drugs, namely the shake-flask method,
      potentiometry, and cyclic voltammetry at liquid-liquid interfaces. The
      lipophilicity of 28 acidic compounds with various functional groups was studied
      by potentiometry and cyclic voltammetry in the n-octanol/water and 1,2
      dichloroethane/water systems in order to complement our understanding of the
      lipophilicity of neutral and ionized acids and to clarify the solvation
      mechanisms responsible for their partition. The parameter diff (log P(N-A)(dce))
      (i.e., log P of the neutral acid minus standard log P of the conjugated anion in
      1,2-dichloroethane/water) was shown to depend not only on intramolecular
      interactions and conformational effects in the neutral and anionic forms, but
      also on the delocalization of the negative charge in the anion, confirming the
      ability of Born's solvation model to describe qualitatively the effect of the
      molecular radius on the lipophilicity of ions.

PMID- 12203329
TI  - Metal complexes of porphycene, corrphycene, and hemiporphycene: stability and
      coordination chemistry.
AB  - Porphyrin (P), porphycene (Pc), corrphycene (Cn), and hemiporphycene (Hpc)
      represent a series of well defined "4-N in" constitutional porphyrin isomers.
      These isomers, in the form of their octaethyl derivatives, represent a congruent
      set of porphyrinoids whose properties can be compared. In this study we report
      how variations in electronic structure and nitrogen-core size in the free-base
      forms of these four systems are reflected in the properties of their
      corresponding metal complexes. Specifically, the effects that these differences
      have on the axial ligation properties of the Zn(II), Mg(II), Ni(II), and Co(II)
      complexes of P, Pc, Cn, and Hpc in toluene using pyridine as the axial ligand are
      detailed. Also reported are the relative stabilities of these complexes under
      acidic conditions. It is shown that for the zinc, magnesium, and cobalt
      complexes, there are distinct differences in the ability to maintain four-, five
      , or six-coordinate geometries in the presence of similar concentrations of
      pyridine. By contrast, no apparent differences in axial ligand binding affinity
      are seen for the four nickel complexes. Little difference in stability was
      likewise seen when these same complexes were subject to acid-mediated
      demetallation, with all four falling into stability class II, according to the
      accepted porphyrin stability ranking system. High stabilities were also seen in
      the case of the cobalt complexes, with the Pc and Cn complexes being of stability
      class III and the P and Hpc derivatives falling into stability class II. The
      Zn(II) and Mg(II) complexes were all far less stable than the corresponding
      Ni(II) and Co(II) complexes. In this case, semiquantitative analyses of the rate
      of acid-induced decomposition revealed the following stability sequence
      P>Cn>Hpc>Pc for both the Zn(II) and Mg(II) complexes. Single-crystal X-ray
      diffraction structures were solved for the Zn(II), Mg(II), and Ni(II) complexes
      of the octaethyl derivatives of Hpc, Cn, and Pc as well as a Co(II)
      octamethylcorrphycene and are reported as part of this study. These solid-state
      structures confirm four-coordinate species for the Ni(II) complexes, four- and
      five-coordinate species for the Mg(II) and Zn(II) complexes, and a six-coordinate
      species for the lone Co(II) complex.

PMID- 12203330
TI  - Towards rational syntheses of the elusive metallocarbohedrenes: density
      functional prescriptions for electronic and geometric structures.
AB  - The metallocarbohedrenes are binary molecular clusters containing metal atoms
      linked by acetylenediide C(2) groups. Hundreds of these molecules have been
      generated, detected and reacted in the gas phase since the prototype,
      [Ti(8)(C(2))(6)], was reported in 1992, but none has yet been synthesised pure in
      bulk: the time gap between detection and preparation increasingly exceeds that of
      the fullerenes. We report here the results of density functional calculations of
      geometrical and electronic structure of more than 150 postulated
      metallocarbohedrenes, stabilised by terminal ligation, in order to recognise the
      more electronically favourable and less reactive targets. At least 38
      metallocarbohedrenes have been identified as having a spin singlet ground state,
      with a relatively large (> 0.5 eV) energy gap between HOMO and LUMO, and an
      appropriate HOMO energy. In addition, a considerable number of electronically
      stable metallocarbohedrenes are predicted to have highly paramagnetic ground
      states, potentially useful in molecular magnetism. The geometrical principles for
      enclosing but unstrained coordination of metal sites by terminal ligands are
      outlined. Mechanisms for rational syntheses are considered in the context of
      reaction type and precursor selection, including issues of oxidation and
      reduction, and kinetic versus thermodynamic control. This leads to many diverse
      reactions suggested for the rational syntheses of metallocarbohedrenes. Some
      preliminary experimental results are presented.

PMID- 12203331
TI  - Electron distribution and molecular motion in crystalline benzene: an accurate
      experimental study combining CCD X-ray data on C6H6 with multitemperature neutron
      diffraction results on C6D6.
AB  - The electronic properties of the benzene molecule, for example its quadrupole
      moment and the electric field gradients (EFG's) at the H nuclei, are of
      fundamental importance in theoretical and experimental chemistry. With this in
      mind, single-crystal X-ray diffraction data on C(6)H(6) were collected with a
      charge-coupled device detector at T approximately 110 K. As accurate modelling of
      the thermal motion in the crystal was regarded as vital, especially for the
      hydrogen atoms, anisotropic-displacement parameters (ADP's) for the C and H atoms
      in C(6)H(6) were derived in a straightforward fashion from analysis of the
      temperature dependence of ADP's for the C and D atoms in C(6)D(6) at 15 K and 123
      K obtained by neutron diffraction. Agreement between C-atom ADP's derived from
      thermal-motion analysis of neutron data and those obtained from multipole
      refinement by using the X-ray data is extraordinarily good; this gives confidence
      in the modelling of vibrational motion for the H atoms. The molecular quadrupole
      moment derived from the total charge density of the molecule in the crystal is (
      29.7+/-2.4)x10(-40) C m(2), in excellent agreement with measurements made in the
      gas phase and in solution. The average deuterium nuclear quadrupole coupling
      constant (DQCC) derived from EFG tensors at H atoms is 182+/-17 kHz, also in
      excellent agreement with independent measurements. The strategy employed in this
      work may be of more general applicability for future accurate electron density
      studies.

PMID- 12203332
TI  - The anatomy of the energetics of molecular recognition by calorimetry: chiral
      discrimination of camphor by alpha-cyclodextrin.
AB  - The molecular recognition of both camphor enantiomers 2 with the chiral alpha
      cyclodextrin (alpha-CD) 1 in water and D(2)O was examined by calorimetry. On the
      basis of statistically supported determinations the thermodynamics of 2:1 host
      guest binding and chiral discrimination was evaluated. The energetic signature
      strongly supports hydrophobic interaction as the dominant driving force for
      camphor encapsulation by alpha-CD in water. The solvent isotope effect on the
      binding equilibrium served to dissect the experimental enthalpy DeltaH(ass) into
      direct interaction (DeltaH(intr)) and solvent reorganization (DeltaH(solv))
      terms. From this analysis the mutual interaction of two cyclodextrin and one
      camphor molecules contributes only 25 % to the observed enthalpy of binding
      DeltaH(ass), all the rest is attributed to solvent restructuring. Furthermore,
      the dramatic change in the pattern of thermodynamic state functions on solvent
      transfer from water to D(2)O is taken as compeling evidence for the involvement
      of water as a structural tectone in the supramolecular architecture of the 2:1
      complex. As a corollary, bilateral host-guest interactions as conveyed by the
      lock-and-key metaphor of molecular recognition provide an inadequate description
      of this seemingly simple artificial host-guest system.

PMID- 12203333
TI  - A density functional study of phosphorus nitride P3N5: refined geometries,
      properties, and relative stability of alpha-P3N5 and gamma-P3N5 and a further
      possible high-pressure phase delta-P3N5 with kyanite-type structure.
AB  - The crystal structures and the enthalpy-pressure phase diagram of P(3)N(5) were
      investigated by using density functional methods. Applying both approximations to
      the electron exchange and correlation gives a consistent picture for the two
      known polymorphs, alpha-P(3)N(5) and gamma-P(3)N(5). The calculated zone-center
      phonon modes compare very well with the experimental results. They indicate low
      frequency bending modes for two-coordinate N atoms of alpha-P(3)N(5), which are
      responsible for a C2/c --> C c structural modulation of alpha-P(3)N(5) at
      moderate pressures. alpha-P(3)N(5) transforms into gamma-P(3)N(5) at pressures of
      about 6 GPa. We propose gamma-P(3)N(5) transforms into a delta-P(3)N(5) with
      Kyanite-type structure at pressures exceeding 43 GPa. Upon quenching, this
      triclinic modification of P(3)N(5) is likely to distort into a more symmetric
      monoclinic structure.

PMID- 12203334
TI  - Mass spectrometric characterization and gas-phase chemistry of self-assembling
      supramolecular squares and triangles.
AB  - A detailed mass spectrometric characterization of self-assembling polynuclear
      metal complexes is described. The complexes can only be ionized as intact species
      under a surprisingly narrow range of conditions by electrospray ionization.
      Comparison with the results from NMR experiments shows that several solution
      phase features of these squares and triangles (such as trends in bond energies,
      ligand-exchange reactions, or square-triangle equilibria) are qualitatively
      reflected in the gas-phase data. Consequently, mass spectrometry represents a
      valuable method for the characterization of these compounds. Nevertheless, the
      formation of unspecific aggregates during the ionization process occurs and its
      implications are discussed. Beyond the chemistry in solution, the fragmentation
      pathways of these complexes in the gas phase have been studied by infrared
      multiphoton dissociation (IRMPD) experiments. The results of IRMPD studies allow
      us to draw conclusions with respect to the structure and energetics of
      fragmentation products. In this tandem MS experiment, reaction pathways can be
      observed directly which can hardly be analyzed in solution. According to these
      results, the equilibration of triangles and squares involves the supramolecular
      analogue of a neighboring-group effect.

PMID- 12203337
TI  - Tag-reporter and resin capture--release strategy in oligosaccharide synthesis.
AB  - Low molecular weight poly(ethylene glycol) (LWPEG) has been found to be useful as
      a "tag" in oligosaccharide synthesis due to its high polarity. Real-time reaction
      monitoring was achieved by use of MALDI-TOF MS in the glycosylation reactions and
      color tests in the deprotection of the chloroacetyl group. Further, a cysteine
      supported insoluble resin enables the purification of the chloroacetyl-bound
      compounds on soluble PEG.

PMID- 12203338
TI  - Control of polymer topology by chain-walking catalysts.
AB  - Chain-walking catalysts are demonstrated to control the branching topology of
      polyethylene by tuning the competition between monomer insertion and chain
      isomerization (walking). The topology of the polyethylene was controlled from
      linear with moderate branching to hyperbranched to dendritic. Although overall
      branching number and distribution of short chain branching are relatively
      constant, the topology of the polyethylene changes from linear polyethylene with
      moderate branches at high ethylene pressures to a dendritic polyethylene at low
      pressures. This provides a straightforward one-pot process for making polymers
      with a full range of tunable topologies.

PMID- 12203339
TI  - Ta97Te60: a crystalline approximant of a tantalum telluride quasicrystal with
      twelvefold rotational symmetry.
AB  - The crystal structure of a rational approximant of an unprecedented dodecagonal
      quasicrystal is reported. The atomic arrangement of the tantalum-rich telluride
      Ta(97)Te(60) has been determined from 30 458 symmetrically independent X-ray
      intensities of a crystal twinned by metric merohedry: a=2767.2(2), b=2767.2(2),
      c=2061.3(2) pm, space group P2(1)2(1)2(1), Pearson symbol oP628, 1415 variables,
      R(F)=0.059. A dodecagonal-shaped, vaulted Ta(151)Te(74) cluster with maximum
      symmetry 6mm can be seen as a characteristic motif of the structure. Each cluster
      measures about 2.5 nm across and consists of nineteen concentrically condensed
      hexagonal antiprismatic Ta(13) clusters which are capped with Te atoms. The
      Ta(151)Te(74) clusters can cover the plane distinctly in different ways, thereby
      forming a series of phases which are closely related both structurally and
      compositionally. In Ta(97)Te(60) the buckled clusters decorate the vertices of a
      square tiling at a 2 nm length scale to result in corrugated
      (infinity)(2)[Te(30)Ta(41)Ta(15)Ta(41)Te(30)] each about 1 nm thick. The lamellae
      are stacked along the c axis, corresponding to the direction of the pseudo
      twelvefold axis of symmetry. Symmetry arguments are proposed that the twinning of
      the structure may be associated with a fine-tuning of weak interlayer Te-Te
      interactions which are reflected in a minimization of the deviation from the mean
      distance <d(Te-Te)> and a doubling of the stacking vector c.

PMID- 12203340
TI  - (Eta3-phenylallyl)(phosphanyloxazoline)palladium complexes: X-ray
      crystallographic studies, NMR investigations, and Ab initio/DFT calculations.
AB  - All possible (eta(3)-allyl)palladium complexes (1-4) of the ligand (4S)-[2-(2'
      diphenylphosphanyl)phenyl]-4,5-dihydro-4-(2-propyl)-oxazole (L 1) and eta(3)
      allyl ligands with one to three phenyl substituents at the terminal allylic
      centers were synthesized and characterized by X-ray crystal structure analysis
      and, with respect to allylic isomers, by NMR investigations. Equilibrium
      geometries, electronic structures, and relative energies of isomeric complexes
      were computed by restricted Hartree-Fock (RHF) and density functional theory
      (DFT) calculations; experimentally determined isomer ratios could be reproduced.
      The results allowed important conclusions to be drawn regarding the mechanism of
      Pd-catalyzed asymmetric allylic substitutions.

PMID- 12203341
TI  - Electrochemical cleavage of N=N bonds at a Mo2(mu-SMe)3 site relevant to the
      biological reduction of dinitrogen at a bimetallic sulfur centre.
AB  - The reduction of diazene complexes [Mo(2)Cp(2)(mu-SMe)(3)(mu-eta(2)-H-N=N-R)](+)
      (R=Ph (3 a); Me (3 b)) and of the hydrazido(2-) derivative [Mo(2)Cp(2)(mu
      SMe)(3)[mu-eta(1)-N=N(Me)H]](+) (1 b) has been studied by cyclic voltammetry,
      controlled-potential electrolysis, and coulometry in THF. The electrochemical
      reduction of 3 a in the presence of acid leads to cleavage of the N=N bond and
      produces aniline and either the amido complex [Mo(2)Cp(2)(mu-SMe)(3)(mu-NH(2))] 4
      or the ammine complex [Mo(2)Cp(2)(mu-SMe)(3)(NH(3))(X)] 5, depending on the
      initial concentration of acid (HX=HTsO or CF(3)CO(2)H). The N=N bond of the
      methyldiazene analogue 3 b is not cleaved under the same conditions. The ability
      of 3 a but not 3 b to undergo reductive cleavage of the N=N bond is attributed to
      electronic control of the strength of the Mo-N(R) bond by the R group. The
      electrochemical reduction of the methylhydrazido(2-) compound 1 b in the presence
      of HX also results in cleavage of the N=N bond, with formation of methylamine, 4
      (or 5) and the methyldiazenido complex [Mo(2)Cp(2)(mu-SMe)(3)(mu-eta(1)-N=N-Me)].
      Formation of the last of these complexes indicates that two mechanisms (N=N bond
      cleavage and possibly H(2) production) are operative. A pathway for the reduction
      of N(2) at a dinuclear site of FeMoco is proposed on the basis of these results.

PMID- 12203342
TI  - Structural and dynamic studies on amido-bridged rhodium and iridium complexes.
AB  - Treatment of [[M(mu-Cl)(diolefin)](2)] with the lithium salts of primary and
      secondary amines (LiNRR') in diethyl ether affords the complexes [[M(mu
      NRR')(diolefin)](2)] (M=Rh, Ir; diolefin=1,5-cyclooctadiene (cod),
      tetrafluorobenzobarrelene (tfb); R'=H, R=tBu, Ph, 4-MeC(6)H(4); R=R'=Ph, 4
      MeC(6)H(4)). Mixed-bridged chloro/amido complexes are intermediates in these
      syntheses, two of which, [[Rh(cod)](2)(mu-NHR)(mu-Cl)] (R=tBu, 4-MeC(6)H(4)),
      have been isolated. Replacement of the diolefin ligands by carbon monoxide or
      tert-butyl isocyanide in selected compounds takes place with retention of the
      binuclear structure to give the corresponding complexes [[M(mu-4
      HNC(6)H(4)Me)(CO)(2)](2)], [[Rh(mu-4-HNC(6)H(4)Me)(CNtBu)(2)](2)] (12), and
      [[Rh(mu-NPh(2))(CNtBu)(2)](2)] (13). Single-crystal X-ray diffraction analyses of
      the complexes [[Rh(mu-NRR')(cod)](2)] (R'=H, R=4-MeC(6)H(4) (3); R=R'=4
      MeC(6)H(4) (5)), 12, and 13 have shown that the conformation of the "RhN(2)Rh"
      four-membered metallacycle is planar in 5 and folded in 3, 12, and 13. The
      complexes with primary amides, 3 and 12, were found to exist as the syn,endo
      stereoisomers. The fluxionality of the complexes with secondary amides is due to
      rotation of the aromatic substituents about the N-C(ipso) bond and, in the case
      of 13, to the inversion of the "RhN(2)Rh" metallacycle as well. The complexes
      [[M(mu-NHR)(cod)](2)] (R=Ph, 4-MeC(6)H(4)) were found to exist as isomeric
      mixtures in solution, the syn/anti ratio being 2:3 for the rhodium derivatives
      and 1:1 for their iridium counterparts. Again, the motion detected was due to
      rotation of the aromatic substituents, and could be frozen only in the case of
      the syn isomers. The complex [[Rh(mu-NHtBu)(cod)](2)] with aliphatic amido
      ligands was found to be the anti folded isomer and proved to be nonfluxional. The
      most common conformation of the "RhN(2)Rh" metallacycle in these compounds is
      folded, and the preferred configuration varies from syn for the less encumbered
      compounds to anti on increasing the bulkiness of the bridging and ancillary
      ligands.

PMID- 12203343
TI  - Diastereoselectivity in the addition of allylzinc reagents to delta-alkoxy
      gamma,delta-disubstituted alkenyllithium compounds.
AB  - The carbometalation reaction of allyl- and crotylzinc bromide with metalated
      disubstituted homoallylic ethers gives tri- or tetrasubstituted 5-hexenyl ethers
      with excellent control of the diastereoselectivity. The stereochemistry of this
      reaction is discussed and has been attributed to an early transition state with
      chelation to the oxygen atom in the energetically favored conformer as the
      stereodetermining step.

PMID- 12203344
TI  - Calix[6]pyrrole and hybrid calix[n]furan[m]pyrroles (n+m=6): syntheses and host
      guest chemistry.
AB  - Calix[6]pyrrole 2 and the "hybrid systems" calix[3]furan[3]pyrrole 12,
      calix[2]furan[4]pyrrole 13, and calix[1]furan[5]pyrrole 14, have been synthesized
      by increasing conversion of the furan units present in the readily accessible
      calix[6]furan 3 to pyrroles. The host-guest chemistry of these novel macrocycles
      towards a number of anions, including halogen ions, dihydrogen phosphate,
      hydrogen sulfate, nitrate, and cyanide has been investigated in solution by (1)H
      NMR titration techniques and/or phase transfer experiments. The solid-state
      structures of the free receptors 2, 12, and 13, the 1:1 complexes of
      calix[6]pyrrole 2 with chloride and bromide, and the 1:1 complex of 14 with
      chloride are also reported.

PMID- 12203345
TI  - The cyano nitronyl nitroxide radical: experimental and theoretical evidence for
      the fourth case of the McConnell-I mechanism.
AB  - The nitronyl nitroxide 2-cyano-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide (1)
      crystallises in the tetragonal P42(1)m space group with a=7.4050(7), c=8.649(1)
      A. In the crystal the molecules form layers parallel to the ab plane in which
      they are orthogonal to each other. In the layers there are close contacts,
      2.953(2) A, between the NO groups and the bridging carbon atoms of the O-N-C-N-O
      fragment of neighbouring radicals. The calculated spin density shows a positive
      population mainly and equally localised on the NO groups and small but
      significant negative spin densities on the bridging carbon atom and the cyano
      nitrogen. Absorption spectra show temperature-dependent transitions related to
      the magnetic behaviour. The temperature dependence of the magnetic susceptibility
      in the range 2-300 K reveals that couplings between the radicals are
      antiferromagnetic, and is interpreted by considering a two-dimensional square
      array of spin S=1/2 antiferromagnetically coupled (J=-10 cm(-1) and g=2.01). This
      is interpreted as an exchange coupling through close contact between positive and
      negative spin densities in orthogonal orbitals on oxygen and carbon atoms,
      respectively.

PMID- 12203346
TI  - Triarylpyridinium-functionalized terpyridyl ligand for photosensitized
      supramolecular architectures: intercomponent coupling and photoinduced processes.
AB  - The electronic (absorption spectra) and electrochemical properties of a novel
      series of triphenylpyridinium (H(3)TP(+)=A) electron-acceptor-based polyad
      species have been correlated with their steady-state (emission spectra) and time
      resolved (ns and ps laser flash photolysis) photophysical behavior (at both 293
      and 77 K). These d(6) transition metal complexes (M=Ru(II), Os(II)) of 2,2':6',2"
      terpyridines (tpy) are denoted as P0 and P1, depending on whether they
      incorporate H(3)TP(+)-tpy or H(3)TP(+)-ptpy ligands (ptpy=4'-phenyl-substituted
      tpy), respectively. For the P0/Ru-based compounds, the luminescence quantum yield
      and excited-state lifetime of the "[Ru(tpy)(2)](2+)" chromophore have been found
      to be considerably enhanced at 293 K (e.g., tau=0.56 ns for isolated P0/Ru in
      acetonitrile vs tau=55 and 27 ns for P0/Ru within P0 A/Ru and P0 A(2)/Ru
      (A=electron acceptor), respectively). In spite of the lack of conjugation between
      P0 and A, this behavior has been ascribed to a through-bond mediated electronic
      substituent effect originating from the directly connected H(3)TP(+) electron
      withdrawing group. For the P1-based compounds, the possibility of photoinduced
      electron-transfer (PET) processes with the formation of charge-separated (CS)
      states is discussed, and the main results may be summarized as follows: 1) when
      involved, the electron-donor D (D=Me(2)N of Me(2)N-ptpy) is strongly
      electronically coupled to P1 but cannot facilitate a reductive quenching of *P1
      to give the *[D(+)-P1(-)]-type of CS state for thermodynamic reasons,
      irrespective of whether M is Ru(II) or Os(II); 2) the P1 and A components have
      been shown to be very weakly electronically coupled; 3) at 293 K, P1/Ru- and
      P1/Os-based polyad systems display distinct photophysical behavior with respect
      to A, with only the latter exhibiting a noticeable quenching of luminescence (up
      to 50 % for P1 A/Os with respect to P1/Os); 4) for assemblies made up of P1/Os
      and A components only, comparison between their room-temperature (RT) and low
      temperature (LT; 77 K, frozen matrix) photophysical properties, together with
      information gleaned from combined transient absorption experiments and
      spectroelectrochemical studies of P1/Os and P1 A/Os, further supported by
      thermodynamic considerations, allowed us to conclude that a PET process does take
      place within the P1 A/Os dyad leading to the *[P1(+)-A(-)] CS state. For the DP1
      A/Os triad, the formation of such a CS state followed by an enhanced electron
      releasing inductive effect from D is postulated.

PMID- 12203347
TI  - Ab initio studies on the mechanism of the size-dependent hydrogen-loss reaction
      in Mg+(H2O)n.
AB  - The mechanism of size-dependent intracluster hydrogen loss in the cluster ions
      Mg(+)(H(2)O)(n), which is switched on around n=6, and off around n=14, was
      studied by ab initio calculations at the MP2/6-31G* and MP2/6-31G** levels for
      n=1-6. The reaction proceeds by Mg(+)-assisted breaking of an H-O bond in one of
      the H(2)O molecules. The reaction barrier is dependent on both the cluster size
      and the solvation structure. As n increases from 1 to 6, there is a dramatic drop
      in the reaction barrier, from greater than 70 kcal mol(-1) for n=1 to less than
      10 kcal mol(-1) for n=6. In the transition structures, the Mg atom is close to
      the oxidation state of +2, and H(2)O molecules in the first solvation shell are
      much more effective in stabilizing the transition structures and lowering the
      reaction barriers than H(2)O molecules in the other solvation shells. While the
      reaction barrier for trimer core structures with only three H(2)O molecules in
      the first shell is greater than 24 kcal mol(-1), even for Mg(+)(H(2)O)(6), it
      drops considerably for clusters with four-six H(2)O molecules in the first shell.
      The more highly coordinated complexes have comparable or slightly higher energy
      than the trimer core structures, and the presence of such high coordination
      number complexes is the underlying kinetic factor for the switching on of the
      hydrogen-loss reaction around n=6. For clusters with trimer core structures, the
      hydrogen loss reaction is much easier when it is preceded by an isomerization
      step that increases the coordination number around Mg(+). Delocalization of the
      electron on the singly occupied molecular orbital (SOMO) away from the Mg(+) ion
      is observed for the hexamer core structure, while at the same time this isomer is
      the most reactive for the hydrogen-loss reaction, with an energy barrier of only
      2.7 kcal mol(-1) at the MP2/6-31G** level.

PMID- 12203348
TI  - Syntheses, crystal structures, and physical properties of dinuclear copper(I) and
      tetranuclear mixed-valence copper(I,II) complexes with hydroxylated bipyridyl
      like ligands.
AB  - Four copper complexes with hydroxylated bipyridyl-like ligands, namely
      [Cu(2)(ophen)(2)] (1), [Cu(4)(ophen)(4)(tp)] (2), [Cu(4)(obpy)(4)(tp)] (3), and
      [Cu(4)(obpy)(4)(dpdc)].2H(2)O (4), (Hophen=2-hydroxy-1,10-phenanthroline, Hobpy=6
      hydroxy-2,2'-bipyridine, tp=terephthalate, dpdc=diphenyl-4,4'-dicarboxylate) have
      been synthesized hydrothermally. X-ray single-crystal structural analyses of
      these complexes reveal that 1,10-phenanthroline (phen) or 2,2'-bipyridine (bpy)
      ligands are hydroxylated into ophen or obpy during the reaction, which provides
      structural evidence for the long-time argued Gillard mechanism. The dinuclear
      copper(I) complex 1 has three supramolecular isomers in the solid state, in which
      short copper-copper distances (2.66-2.68 A) indicate weak metal-metal bonding
      interactions. Each of the mixed-valence copper(i,ii) complexes 2-4 consists of a
      pair of [Cu(2)(ophen)(2)](+) or [Cu(2)(obpy)(2)](+) fragments bridged by a
      dicarboxylate ligand into a neutral tetranuclear dumbbell structure. Dinuclear 1
      is an intermediate in the formation of 2 and can be converted into 2 in the
      presence of additional copper(II) salt and tp ligands under hydrothermal
      conditions. In addition to the ophen-centered pi-->pi* excited-state emission, 1
      shows strong emissions at ambient temperature, which may be tentatively assigned
      as an admixture of copper-centered d-->s,p and MLCT excited states.

PMID- 12203349
TI  - Completely spirocyclopropanated macrocyclic oligodiacetylenes and their
      permethylated analogues: preparation and properties.
AB  - The acyclic dehydrotrimer (12) and -hexamer (28) of 1,1-diethynyl-2,2,3,3
      tetramethylcyclopropane were prepared from 1-chloro-1-(trimethylsilylethynyl)
      2,2,3,3-tetramethylcyclopropane (4) in six and nine steps, respectively, in 36
      and 8 % overall yield, respectively, using Cadiot-Chodkiewicz or Hay coupling
      procedures as key steps. Mono-tert-butyldimethylsilyl (TBDMS) protection of the
      acyclic dehydrotrimer (20) and -hexamer (23) of 1,1-diethynylcyclopropane
      followed by Hay coupling and protiodesilylation furnished the acyclic
      dehydrohexamer (23) and -dodecamer (29) in 35 and 56 % overall yield,
      respectively. Subsequent cyclizing oxidative dimerization of 12 or cyclization of
      28 using a modified Glaser protocol produced the first completely
      permethylspirocyclopropanated macrocyclic oligodiacetylene, compound 30 in 49 and
      21 % yield, respectively. The cyclic dehydrohexa- (31) and dehydrododecamer (32)
      have been prepared from 23 and 29 in 49 and 7 % yield by applying the same
      protocol. The macrocycle 32 is particularly interesting in that it contains 60
      carbon atoms in the inner ring, and indeed a decomposition mode consecutively
      cleaving off ethylene units from it as well as from 31 and tetramethylethylene
      from the permethylated exp-[6]rotane 30 has been proved by differential scanning
      calorimetry with evolved gas analysis. The thermal decomposition of these
      "exploding" [6]rotanes 31 and 30 set on at 100 and 135 degrees C, respectively,
      and release energies of 478 and 285 kcal. mol(-1), respectively, significantly
      more than the energy release of the explosive hexogen with 143 kcal mol(-1).

PMID- 12203350
TI  - Generic phase behavior of branched-chain phospholipid monolayers.
AB  - Monolayers of chemically modified triple-chain phospholipids have been
      investigated at the air/water interface using pressure-area isotherms. The
      condensed phases of the lipids were characterized by grazing incidence X-ray
      diffraction (GIXD). Increasing chain length corresponds to a temperature effect,
      which was quantified for different lipids, depending on the head group structure
      using isotherm (two-dimensional systems) and DSC (three-dimensional systems)
      measurements. The combination of structure investigations revealed generic phase
      diagrams, which describe the phase behavior of multiple-chain lipids in two
      dimensions. For the 1-acyl-2-O-alkyl phospholipids, the generic phase diagram
      exhibits only L(2d), LS and LE phases while the exchange of the position of the
      branched acyl and the non-branched alkyl chains at the glycerol backbone leads to
      a much richer polymorphism (L(2h), L(2d), Ov, LS, S, tau, LE). Here we present
      the first experimental evidence of the unusual tau phase for multiple-chain lipid
      monolayers. This phase exhibits an undistorted in-plane lattice despite of tilted
      chains.

PMID- 12203351
TI  - Enzyme fingerprints of activity, and stereo- and enantioselectivity from
      fluorogenic and chromogenic substrate arrays.
AB  - A series of stereochemically and structurally diverse fluorogenic and chromogenic
      substrates for hydrolytic enzymes has been synthesized and used to characterize
      enzyme activity profiles of esterases, lipases, proteases, peptidases,
      phosphatases, and epoxide hydrolases. The substrates used are particularly
      resilient to nonspecific reactions due to their mechanism of activation. The
      activities recorded with the individual substrates are therefore remarkably
      reproducible, and enable us to use the overall pattern of activity as a specific
      fingerprint for the enzyme sample. Fingerprints of activity, and enantio- and
      stereoselectivity are displayed as arrays of color-scale squares that are easily
      analyzed visually. Such fingerprints might be useful for quality control, enzyme
      discovery, and possibly for addressing the issue of functional convergence in
      enzymes.

PMID- 12203352
TI  - Schlenk's early "free" carbanions.
AB  - Nearly a century ago, Schlenk published the syntheses and isolation of two most
      remarkable and unstable complexes: crystalline [Ph(3)C(-)][Me(4)N(+)] and
      [PhCH(2) (-)][Me(4)N(+)]. The crystal structure of the first complex contains a
      "free" Ph(3)C(-) ion, which displays the expected planar trigonal geometry at its
      central carbon atom. The phenyl groups are not orientated in the typical
      propeller arrangement, but instead display various orientations with respect to
      the molecular plane. These orientations can be directly related to the extent of
      charge delocalization and correlate well with other structural characteristics
      related to charge delocalization. The crystal structure also shows a network of C
      H(delta+)...C(delta-) and C-H...pi interactions. Only C-H...pi interactions to
      the most negative charged phenyl rings are observed. The absolute Bronsted
      acidity of Me(4)N(+) is calculated by the G2(MP2) method (287.7 kcal mol(-1)) and
      is compared to the calculated acidity of Me(4)P(+) (268.4 kcal mol(-1)). On this
      basis, the pK(a) value for Me(4)N(+) is estimated at 29.6. This makes the
      existence, and especially Schlenk's early isolation, of the "free" carbanions
      [Ph(3)C(-)][Me(4)N(+)] and [PhCH(2) (-)][Me(4)N(+)] quite noteworthy.

PMID- 12203353
TI  - Structure validation of natural products by quantum-mechanical GIAO calculations
      of 13C NMR chemical shifts.
AB  - Geometry optimization and GIAO (gauge including atomic orbitals) (13)C NMR
      chemical shift calculations at Hartree-Fock level, using the 6-31G(d) basis set,
      are proposed as a tool to be applied in the structural characterization of new
      organic compounds, thus providing useful support in the interpretation of
      experimental NMR data. Parameters related to linear correlation plots of computed
      versus experimental (13)C NMR chemical shifts for fourteen low-polar natural
      products, containing 10-20 carbon atoms, were employed to assess the reliability
      of the proposed structures. A comparison with the hybrid B3LYP method was carried
      out to evaluate electron correlation contributions to the calculation of (13)C
      NMR chemical shifts and, eventually, to extend the applicability of such
      computational methods to the interpretation of NMR spectra in apolar solutions.
      The method was tested by studying three examples of revised structure
      assignments, analyzing how the theoretical (13)C chemical shifts of both correct
      and incorrect structures matched the experimental data.

PMID- 12203354
TI  - Determination of the relative stereochemistry of flexible organic compounds by Ab
      initio methods: conformational analysis and Boltzmann-averaged GIAO 13C NMR
      chemical shifts.
AB  - Ab initio calculations at the Hartree-Fock level with full-geometry optimization
      using the 6-31G(d) basis set, and GIAO (gauge including atomic orbitals) (13)C
      NMR chemical shifts, are presented here as a support in the study of the
      stereochemistry of low-polar organic compounds having an open-chain structure.
      Four linear stereoisomers, fragments of a natural product previously
      characterized by experimental (13)C NMR spectra, which possesses three
      stereogenic centers, 11 carbon atoms, and 38 atoms in total, were considered.
      Conformational searches, by empirical force-field molecular dynamics, pointed out
      the existence of 8-13 relevant conformers per stereoisomer. Thermochemical
      calculations at the ab initio level in the harmonic approximation of the
      vibrational modes, allowed the evaluation, at 298.15 K, of the standard Gibbs
      free energy of the conformers. The (13)C NMR chemical shift of a given carbon
      atom in each stereoisomer was considered as the average chemical shift value of
      the same atom in the different conformers. The averages were obtained by the
      Boltzmann distribution, using the relative standard free energies as weighting
      factors. Computed parameters related to linear correlation plots of experimental
      (13)C chemical shifts versus the corresponding computed average data allowed us
      to distinguish among the four stereoisomers.

PMID- 12203355
TI  - Synthesis and characterization of conjugated diblock copolymers.
AB  - This paper reports the synthesis and characterization of a new class of diblock
      copolymers (co-oligomers), rod-rod conjugated diblock copolymers. A general
      synthetic strategy is outlined, and the structures of the copolymers
      (oligothiophene-co-oligophenylenevinylene) are fully characterized. It was found
      that these copolymers exhibit efficient intramolecular energy transfer. An
      interesting self-assembly ability of these rod--rod copolymers was also revealed.

PMID- 12203356
TI  - Crystal engineering of organic clay mimics from 3,5-pyrazoledicarboxylic acid and
      amines.
AB  - The syntheses and crystal structures of sixteen compounds containing the
      monoanion of 3,5-pyrazoledicarboxylic acid (H(2)PzDCA) and ammonium-based
      counterions are reported. The cations contain short-chain alkyl, long-chain
      alkyl, phenyl, and chloro-, methoxy-, and amine-substituted aryl groups. Self
      complementary HPzDCA intermolecular hydrogen bonds create nearly planar sheets,
      to which the cations connect through hydrogen bonds. Twelve of the structures
      exhibit virtually identical hydrogen-bonded layers, but the distance between
      layers varies from 9.33 to 14.10 A (+/-20 %), depending on the cation. The
      comparison of the sixteen structures leads to the identification of a building
      block (HPzDCA) that creates remarkably reproducible, lamellar structures despite
      substantial changes in the counterion.

PMID- 12203357
TI  - Nanoparticles of amorphous ruthenium sulfide easily obtainable from a TiO2
      supported hexanuclear cluster complex [Ru6C(CO)16]2-: a highly active catalyst
      for the reduction of SO2 with H2.
AB  - TiO(2)-supported ruthenium-metal particles were derived from an anionic
      hexanuclear carbido carbonyl cluster [Ru(6)C(CO)(16)](2-) and compared with those
      prepared conventionally by impregnation of TiO(2) with a solution of RuCl(3)
      followed by reduction with H(2). The average sizes of the metal particles in both
      systems are similar, that is, 12 A for molecular cluster-derived particles and 15
      A for those derived from the RuCl(3) precursor, although the size distribution is
      sharper in the former case. These supported particles efficiently promote the
      reduction of SO(2) with H(2) to give elemental sulfur. Their active form is
      ruthenium sulfide as confirmed by EXAFS and X-ray diffraction measurements. The
      nanoscale ruthenium sulfide particles, which originated from the cluster complex,
      have an amorphous character and show activity even at low temperature (463 K),
      whereas ruthenium sulfide formed from RuCl(3)-derived metal dispersion is a
      pyrite-type RuS(2) crystallite and needs a temperature above 513 K to effect the
      same catalysis. Amorphous ruthenium sulfide maintains its nano-sized scale
      (approximately 14 A) regardless of the reaction temperature, while RuS(2)
      crystallite aggregates to form larger nonuniform particles.

PMID- 12203358
TI  - Metal-metal bonds between group 12 metals and tin: structural characterization of
      the complete series of Sn-M-Sn (M=Zn, Cd, Hg) heterodimetallic complexes.
AB  - Reaction of the lithium triamidostannate [MeSi[SiMe(2)N(p-Tol)](3)SnLi(OEt(2))]
      (1) with 0.5 molar equivalents of MCl(2) (M=Zn, Cd, Hg) in toluene afforded the
      corresponding heterodimetallic complexes [MeSi[SiMe(2)N(p-Tol)](3)Sn](2)M [M=Hg
      (2), Cd (3), and Zn (4)]. The molecular structures of the mercury and cadmium
      complexes were determined by X-ray diffraction and found to adopt a linear Sn-M
      Sn metal-metal bonded array (d(Sn-Hg) 2.6495(2), d(Sn-Cd) 2.6758(1) A), these
      being the first Hg-Sn and Cd-Sn bonds to be characterized by X-ray diffraction.
      That the Hg-Sn bonds are shorter than the Cd-Sn bonds in the isomorphous
      complexes is attributed to relativistic effects in the mercury system. In
      contrast, the structure of the Zn analogue is unsymmetrical with one stannate
      unit being Sn-Zn bonded (d(Sn(1)-Zn) 2.5782(4) A), while the Zn(II) atom bridges
      two amido functions of the second stannate cage, thus representing a second
      isomeric form of these complexes. The different degree of metal-metal bond
      polarity is reflected in the (119)Sn NMR chemical shifts of the three complexes.
      Variable-temperature NMR studies and a series of (1)H ROESY experiments of the
      cadmium complex 3 in solution revealed a dynamic exchange between the two
      isomers.

PMID- 12203359
TI  - Methane activation and oxidation in sulfuric acid.
AB  - The H/D exchange observed when methane is contacted with D(2)SO(4) at 270-330
      degrees C shows that the alkane behaves as a sigma base and undergoes rapid and
      reversible protonation at this temperature. DFT studies of the hydrogen exchange
      between a monomer and a dimer of sulfuric acid and methane show that the
      transition states involved in the exchange are bifunctional, that is one hydrogen
      atom is transferred from a hydroxy group in sulfuric acid to methane, while one
      hydrogen atom is abstracted from methane by a non-hydroxy oxygen atom in sulfuric
      acid. All the transition states include a CH(5) moiety, which shows similarities
      to the methanium ion CH(5) (+). The calculated potential activation energy of the
      hydrogen exchange for the monomer is 174 kJ mol(-1), which is close to the
      experimental value (176 kJ mol(-1)). Solvation of the monomer and the transition
      state of the monomer with an extra sulfuric acid molecule, decrease the potential
      activation energy by 6 kJ mol(-1). The acid-base process is in competition,
      however, with an oxidative process involving methane and sulfuric acid which
      leads to CO(2), SO(2), and water, and thus to a decrease of acidity and loss of
      reactivity of the medium.

PMID- 12203361
TI  - Follistatin overexpression in rodent liver tumors: a possible mechanism to
      overcome activin growth control.
AB  - The activin-follistatin system is a potent growth regulatory system of liver
      tissue homeostasis. Activin A inhibits hepatocellular DNA synthesis and induces
      cell death. Follistatin binds activin and sequesters it from the signaling
      pathway. Consistently, follistatin has been reported to act as an inducer of DNA
      synthesis in the liver. Using RNase protection analysis, we studied the
      expression of follistatin in rat and mouse liver tumors as a possible mechanism
      to overcome activin growth control. Approximately 40% of the tumors (nine of 24
      each), most of them hepatocellular carcinomas, displayed increased levels of
      follistatin mRNA when compared to tumor-surrounding liver tissue. The degree of
      overexpression was highly variable but independent of the carcinogen treatment
      that animals had received. It was also independent from the histological stage of
      malignancy and further found in rat liver adenomas. Follistatin expression was
      also observed in cell lines derived from human hepatocellular carcinomas.
      Overexpression of follistatin may represent a unique strategy of hepatic tumors
      to overcome the inhibitory action of a growth factor, activin, by decreasing its
      local bioavailability.

PMID- 12203362
TI  - CCND1- and ERBB2-gene deregulation and PTEN mutation analyses in invasive lobular
      carcinoma of the breast.
AB  - Because of the relatively low incidence of lobular breast carcinoma, there are
      very few studies on the molecular characteristics of this breast cancer. In an
      attempt to improve its characterization, we investigated in a large collection of
      invasive lobular carcinomas (ILCs) the status of markers known to be involved in
      the better-studied invasive ductal carcinomas (IDC). In the current study we
      disposed of 80 well-characterized ILC cases. Gene amplification of cyclin D1
      (CCND1) and c-erbB2-encoding gene (ERBB2) and expression of their gene products
      were studied by differential polymerase chain reaction (PCR) and
      immunohistochemistry, respectively. A comprehensive point mutation study of the
      phosphatase and tensin homolog tumor suppressor gene (PTEN) was pursued by single
      strand conformation polymorphism (SSCP)/sequencing analysis. The CCND1 gene was
      rarely amplified in ILC in spite of showing overexpression of the protein in 41%
      of tumors. Hence, unlike IDC, increase in gene dosage did not account for the
      protein excess. PTEN mutations were detected in ILC (truncating mutations) in
      around 2% of the tumors. Unlike IDC, ILC did not display ERBB2 overexpression and
      expression of the transcription factor E2F1 correlated inversely with tumor
      grade. The observed discrepancy in the pattern of the human oncogenes CCND1 and
      ERBB2, which are involved in the process of carcinogenesis of ductal tumors,
      appears to suggest a different molecular basis for development and progression of
      ILC.

PMID- 12203363
TI  - Genetic analyses of mouse skin tumor progression susceptibility using SENCAR
      inbred derived strains.
AB  - Susceptibility to tumor development varies among individuals in the human
      population. This variability can also be found among different strains of mice,
      particularly in the mouse skin chemical carcinogenesis model. The genetic
      mechanisms underlying mouse skin tumor susceptibility are not fully understood.
      The SENCAR stock has been found to be the most sensitive mice for skin
      carcinogenesis studies; however, little is known about the genes underlying tumor
      susceptibility, particularly, those involved in tumor progression. Experiments
      with the SSIN/Sprd mice, an inbred strain derived from the outbred SENCAR stock,
      suggested that papilloma development, tumor promotion, and their conversion into
      squamous cell carcinomas (SCCs), progression, are regulated by different genes.
      In the highly sensitive SSIN/Sprd mice, papillomas rarely progress to SCC. Using
      crosses between the outbred SENCAR and the SSIN/Sprd mice, we previously
      determined that papilloma progression in the SENCAR stock could be controlled by
      at least one autosomal dominant gene. However, the outbred nature of the SENCAR
      stock precluded us from extending those findings. More recently, another inbred
      strain was developed from the outbred SENCAR stock, the SENCARB/Pt. These mice
      have similar tumor promotion sensitivity to the SSIN/Sprd but in contrast, have
      high papilloma progression susceptibility, similar to the outbred original stock.
      In the present study, we generated F(1), F(2), and backcross hybrids between the
      SSIN/Sprd and SENCARB/Pt mice to determine a possible model for tumor progression
      susceptibility and to map the putative tumor susceptibility genes. Our tumor data
      suggests that papilloma progression susceptibility in the SENCAR mouse skin model
      could be genetically determined by one susceptibility gene. Our preliminary
      linkage analysis failed to identify one strong susceptibility locus to confirm
      this but provided some evidence for at least one possible susceptibility locus in
      mouse chromosome 14.

PMID- 12203364
TI  - Involvement of both extracellular signal-regulated kinase and c-jun N-terminal
      kinase pathways in the 12-O-tetradecanoylphorbol-13-acetate-induced upregulation
      of p21(Cip1) in colon cancer cells.
AB  - Protein kinase C (PKC), a family of serine-threonine kinases, has been implicated
      in the regulation of colon tumorigenesis. However, the specific isoform of PKC
      involved in this process is not clear. In the present study, we found that
      treatment of the cultured human colon cancer cell line COLO-205 with a PKC
      agonist, 12-O-tetradecanoylphorbol-13-acetate (TPA), resulted in cell-cycle
      arrest at the G(0)/G(1) phase, decrease in cell number, PKCgamma isoform
      translocation, and upregulation of p21(Cip1) protein. Pretreatment of the cells
      with a PKC inhibitor, staurosporine, prevented the TPA-induced upregulation of
      p21(Cip1) protein. Based on the findings of the present study including that (a)
      both extracellular signal-regulated kinase (ERK) and c-jun N-terminal kinase
      (JNK) were activated in the TPA-treated COLO-205 cells, (b) pretreatment with the
      mitogen-activated protein kinase kinase inhibitor PD98059 but not with the p38
      mitogen-activated protein kinase inhibitor SB203580 blocked the TPA-induced
      p21(Cip1) in COLO-205 cells, and (c) transient transfection of the COLO-205 cells
      with dominant negative ERK or JNK plasmid significantly suppressed the TPA
      induced p21(Cip1) protein induction, we conclude that both the ERK and JNK
      pathways are involved in the TPA-induced upregulation of p21(Cip1) protein in the
      COLO-205 cells.

PMID- 12203365
TI  - Inducible expression of the gap junction protein connexin43 decreases the
      neoplastic potential of HT-1080 human fibrosarcoma cells in vitro and in vivo.
AB  - Numerous studies have demonstrated a correlation between dysregulation/loss of
      connexin expression or gap junction intercellular communication (GJIC) function
      and decreased growth control both in human tumors and tumor cell lines. Likewise,
      restoration of constitutive connexin expression/function is correlated with
      increased growth control/decreased tumorigenicity. Here, we show for the first
      time that inducible restoration of connexin43 (Cx43) expression and GJIC function
      in a human tumor line of mesenchymal origin (HT-1080, fibrosarcoma) resulted in a
      lowered neoplastic potential. Specifically, HT-1080 cells induced to express Cx43
      demonstrated diminished foci formation when in co-culture with normal
      fibroblasts, decreased colony formation under anchorage-independent conditions,
      and reduced tumor growth when injected into immunodeficient mice. These results,
      obtained utilizing an inducible system that helps address issues of clonal
      heterogeneity, strongly implicate Cx43 as a tumor suppressor in human tissue of
      mesenchymal origin and GJIC as a regulatory mechanism for cellular growth control
      both in vitro and in vivo. This study also further supports the hypothesis that
      loss of Cx43/GJIC in human tumors may play an important role in the dysregulation
      of normal growth control.

PMID- 12203366
TI  - Evidence of increased Id-1 expression and its role in cell proliferation in
      nasopharyngeal carcinoma cells.
AB  - Inhibitor of differentiation or DNA binding (Id-1), a helix-loop-helix
      transcription factor, has recently been shown to inactivate the retinoblastoma
      (RB)/p16(INK4a) pathway through down-regulation of p16(INK4a) and increasing
      phosphorylation of RB in certain cell types. Nasopharyngeal carcinoma (NPC) is a
      common cancer in Hong Kong, and inactivation of the tumor suppressor RB at
      transcription level is a rare event in NPC. The objective of this study was to
      investigate the role of Id-1 in NPC cell proliferation and its expression in NPC
      samples. An NPC cell line, CNE1, was transfected with a retroviral vector
      containing a full-length Id-1 cDNA, and six stable transfectant clones were
      isolated with differential Id-1 expression levels. The effect of ectopic Id-1
      expression on serum-independent cell growth, cell-cycle distribution, and
      expression of proteins associated with RB pathway was studied. The Id-1
      expression in five NPC samples was also investigated using immunohistochemistry.
      Ectopic Id-1 expression in CNE1 cells resulted in an increase in serum
      independent cell growth, percentage of cells in S phase, and phosphorylation of
      RB and cyclin-dependent kinase 2 proteins. In addition, immunohistochemical
      studies on NPC samples showed that expression of Id-1 was present in NPC cells
      but absent in normal tissues. This study demonstrates that Id-1 plays an
      important role in cell proliferation in NPC cells, and our results provide
      evidence for the first time of the significance of Id-1 expression in NPC cells
      and suggest a possible role of Id-1 expression in the inactivation of RB and
      development of NPC.

PMID- 12203367
TI  - Peroxisome proliferator-activated receptor alpha in the human breast cancer cell
      lines MCF-7 and MDA-MB-231.
AB  - Peroxisome proliferator-activated receptor (PPAR) alpha is a ligand-activated
      transcription factor that has been linked with rodent hepatocarcinogenesis. It
      has been suggested that PPARalpha mRNA expression levels are an important
      determinant of rodent hepatic tumorigenicity. Previous work in rat mammary gland
      epithelial cells showed significantly increased PPARalpha mRNA expression in
      carcinomas, suggesting the possible role of this isoform in rodent mammary gland
      carcinogenesis. In this study we sought to determine whether PPARalpha is
      expressed and dynamically regulated in human breast cancer MCF-7 and MDA-MB-231
      cells. Having established the presence of PPARalpha in both cell types, we then
      examined the consequence of PPARalpha activation, by its ligands Wy-14,643 and
      clofibrate, on proliferation. With real-time reverse transcriptase-polymerase
      chain reaction, we showed that PPARalpha mRNA was dynamically regulated in MDA-MB
      231 cells and that PPARalpha activation significantly increased proliferation of
      the cell line. In contrast, PPARalpha expression in MCF-7 cells did not change
      with proliferation during culture and was present at significantly lower levels
      than in MDA-MB-231 cells. However, PPARalpha ligand activation still
      significantly increased the proliferation of MCF-7 cells. The promotion of
      proliferation in breast cancer cell lines following PPARalpha activation was in
      stark contrast to the effects of PPARgamma-activating ligands that decrease
      proliferation in human breast cancer cells. Our results established the presence
      of PPARalpha in human breast cancer cell lines and showed for the first time that
      activation of PPARalpha in human breast cancer cells promoted proliferation.
      Hence, this pathway may be significant in mammary gland tumorigenesis.

PMID- 12203368
TI  - Tumorigenic effect of transcription factor hAP-2alpha and the intricate link
      between hAP-2alpha activation and squelching.
AB  - Overexpression of human activator protein-2alpha (hAP-2alpha) is carcinogenic.
      Its aberrant regulation is the underlying tumorigenic event in the human
      teratocarcinoma cell line PA-1. In this cell line excess hAP-2alpha protein binds
      and sequesters coactivators, which interferes with the activity of other
      activators and with its own activity. The N-terminus of hAP-2alpha, which
      contains an activation domain, is critical in squelching and tumorigenicity.
      Mutation analyses of the N-terminus region showed that activation and squelching
      were intricately linked; nevertheless, squelching could occur in the absence of
      activity. Cells overexpressing squelching-proficient mutants grew efficiently on
      soft agar irrespective of their ability to activate transcription, which
      indicates that these cells are tumorigenic. Mutants that lacked both properties
      were nontumorigenic. These results suggest that squelching, but not activation,
      causes transformation and that the factors that are sequestered at this region
      are critical in tumorigenesis.

PMID- 12203369
TI  - Enhancement of anchorage-independent growth of human pancreatic carcinoma MIA
      PaCa-2 cells by signaling from protein kinase C to mitogen-activated protein
      kinase.
AB  - We found that 12-O-tetradecanoylphorbol-13-acetate (TPA) promoted anchorage
      independent growth but did not affect anchorage-dependent growth of MIA PaCa-2
      human pancreatic carcinoma cells. TPA markedly activated mitogen-activated
      protein kinase (MAPK)/extracellular signal-regulated kinase in an anchorage
      independent manner. Two protein kinase C (PKC) isoforms, conventional PKC (cPKC)
      and novel PKC (nPKC), but not apical PKC, translocated from the cytosolic to the
      particulate fraction upon TPA treatment. To identify the PKC isoforms involved in
      the regulation of anchorage-independent growth, four PKC isoforms (alpha, delta,
      epsilon, and zeta) were forced to be expressed in MIA PaCa-2 cells with an
      adenovirus vector. Overexpression of nPKCdelta or nPKC epsilon activated MAPK and
      promoted anchorage-independent growth. Overexpression of cPKCalpha alone did not
      influence anchorage-independent growth but lowered the concentration of TPA that
      was required to enhance such growth. Expression of constitutively active MAPK
      kinase-1 (MEK1) also promoted anchorage-independent growth. Furthermore, PKC
      inhibitors or an MEK inhibitor completely suppressed both TPA-induced activation
      of MAPK and promotion of anchorage-independent growth, but a cPKC-selective
      inhibitor partially suppressed TPA-induced promotion of the growth. Based on
      these results, we suggest that MAPK activation, mediated by certain isoforms of
      PKC, plays a part in oncogenic growth of MIA PaCa-2 cells. In summary, our data
      indicated that specific inhibitors of the cPKC and nPKC signaling pathway might
      be selective anti-oncogenic growth agents for some types of human pancreatic
      cancer.

PMID- 12203370
TI  - CpG hypermethylation of promoter region and inactivation of E-cadherin gene in
      human bladder cancer.
AB  - Several studies have shown that E-cadherin expression is lost during malignant
      transformation. We hypothesized that CpG methylation in the promoter region may
      inactivate the expression of the E-cadherin gene in human bladder cancer. Normal
      and bladder cancer samples from 51 patients were compared in terms of E-cadherin
      gene expression and methylation status by immunohistochemistry, methylation
      specific polymerase chain reaction (MSP), and bisulfite genome-sequencing
      techniques. Ten different CpG sites (nt 863, 865, 873, 879, 887, 892, 901, 918,
      920, and 940) in the promoter region were studied. Thirty-five of 51 (69%)
      bladder cancer samples lacked E-cadherin expression, whereas only six of 51 (12%)
      normal bladder samples lacked E-cadherin immunoreactivity. MSP analysis of
      bladder cancer samples suggested that 43 of 51 (84%) showed methylation of the
      promoter region, whereas only 12 of 51 (24%) normal bladder samples showed
      hypermethylation. Sodium bisulfite genome-sequencing analysis revealed that of 10
      CpG sites, two sites (nt 892 and nt 940) showed 100% methylation in all the
      cancer samples analyzed. Other CpG sites were partially methylated (47-91%).
      Normal tissue showed only 12% methylation (range, 1-33%) on various CpG sites.
      Also supporting these data, E-cadherin-negative bladder cancer cell lines
      restored expression of the E-cadherin gene after treatment with the demethylating
      agent 5-aza-2'-deoxycytidine. The present study showed that CpG hypermethylation
      was an important mechanism of E-cadherin gene inactivation in bladder cancer and
      also that specific CpG sites consistently presented higher methylation levels
      than others. These findings may provide a better strategy for the diagnosis and
      management of bladder cancer.

PMID- 12203371
TI  - Ketoconazole potentiates the antitumor effects of nocodazole: In vivo therapy for
      human tumor xenografts in nude mice.
AB  - Our previous studies demonstrated that the oral antifungal agent ketoconazole
      (KT) induces apoptosis and G0/G1 phase cell cycle arrest in human cancer cell
      lines. In this study, we first demonstrated that KT (1 microM) potentiated the
      apoptotic effects of nocodazole (ND, 1 nM) in COLO 205 cancer cells. We further
      demonstrated the therapeutic efficacy of a combined treatment of KT (50
      mg/kg/three times per week) and ND (5 mg/kg/three times per week) in vivo by
      treating athymic mice bearing COLO 205 tumor xenografts. The antitumor effects of
      ND were significantly potentiated by KT in mice after 6 wk of treatment. No gross
      signs of toxicity were observed in mice receiving these treatment regimens. The
      apoptotic cells were detected in a microscopic view of the terminal
      deoxynucleotidyl transferase-mediated dUTP nick-end labeling staining and by
      observation of DNA fragmentation in KT + ND-treated tumor tissues. The levels of
      cell cycle regulatory proteins were determined by Western blot analysis.
      Treatment with KT inhibits tumor growth through elevation of p53, p21/CIP1, and
      p27/KIP1 as well as inhibition of cyclin D3 and cyclin-dependent kinase 4 protein
      expression. Immunohistochemical staining analysis showed that p53, p21/CIP1, and
      p27/KIP1 immunoreactivity were induced in the tumor tissues. To clarify the roles
      of the p21/CIP1 and p27/KIP1 protein expression involved in G(0)/G(1) arrest
      and/or apoptosis induced by a combined treatment with KT and ND, antisense
      oligodeoxynucleotides (ODNs) specific to p21/CIP1 and p27/KIP1 were used. Our
      results demonstrated that apoptotic phenomena, including BAX induction and
      cytochrome C released from mitochondria induced by KT + ND, were significantly
      attenuated by pretreatment the cells with the p27/KIP1-specific antisense ODNs.
      These results indicate that p27/KIP1 protein does indeed play a critical role in
      the KT + ND-induced apoptosis. Our study revealed the molecular mechanism of KT +
      ND in regression of the tumor growth. The apoptotic effects of KT in a great
      variety of cancer cells make it a very attractive agent for cancer chemotherapy.

PMID- 12203374
TI  - Albert Wojciech Adamkiewicz 1850-1921.

PMID- 12203372
TI  - Reduced Brca1 protein expression in 2-amino-1-methyl-6-phenylimidazo[4,5
      b]pyridine-induced rat mammary carcinomas.
AB  - Reduced expression of BRCA1 protein, caused by the hypermethylation of its gene
      promoter and by other mechanisms, is observed in most sporadic human breast
      cancers, whereas its somatic mutations are rare. In the present study, we
      demonstrate that immunoreactivity of Brca1 was reduced in almost all rat mammary
      carcinomas induced by 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP),
      whereas hypermethylation of its promoter, mutations in its entire coding region,
      and decreased mRNA expression were absent. Using two kinds of polyclonal
      antibodies against human BRCA1 that recognized the N and C termini, respectively,
      immunoreactivity of Brca1 was found to be reduced in all 17 carcinomas examined
      and, especially, to be almost completely lost in 8 or 10 carcinomas. The
      reduction was confirmed by immunoblot analysis of five mammary carcinomas and
      normal mammary epithelial cells. Sequencing of the Brca1 promoter region after
      bisulfite modification in 10 PhIP-induced mammary carcinomas showed that the
      region was completely unmethylated in all of them. No mutations were detected in
      the entire coding region by direct sequencing of the Brca1 cDNA. Decrease in mRNA
      levels was not detected by quantitative real-time reverse transcription
      polymerase chain reaction. These data suggested that PhIP-induced mammary
      carcinomas could model human breast cancers that show reduced BRCA1
      immunoreactivity without promoter hypermethylation and with normal mRNA
      expression. As underlying mechanisms, alterations in posttranscriptional
      regulation or stability of Brca1 protein were suggested.

PMID- 12203375
TI  - Anatomy and physiology of the female perineal body with relevance to obstetrical
      injury and repair.
AB  - The female perineal body is a mass of interlocking muscular, fascial, and fibrous
      components lying between the vagina and anorectum. The perineal body is also an
      integral attachment point for components of the urinary and fecal continence
      mechanisms, which are commonly damaged during vaginal childbirth. Repair of
      injuries to the perineal body caused by spontaneous tears or episiotomy are
      topics too often neglected in medical education. This review presents the anatomy
      and physiology of the female perineal body, as well as clinical considerations
      for pelvic reconstructive surgery.

PMID- 12203376
TI  - Morphometric study of testis of Wistar rat after open-ended vasectomy.
AB  - The effects on the testis of open-ended vasectomy in the Wistar rat have been
      assessed morphometrically and evaluated statistically at 1, 4, 12, and 24 weeks
      after operation, and compared to those in sham-operated controls. The open-ended
      technique, ie, without ligation of the epididymal end of the cut ductus deferens,
      allowed drainage of sperm into the spermatic cord. During the period of our
      study, it did not affect the structure of the testis; although the germinal
      epithelium, basement membrane, and the stroma and cells of the interstitial space
      all showed variations when compared to the control group, these were not
      statistically significant.

PMID- 12203377
TI  - Pathways of anesthetic from the thoracic paravertebral region to the celiac
      ganglion.
AB  - Communication between the lower thoracic paravertebral region and the celiac
      ganglion through the retrocrural space was investigated. After dye was injected
      into the endothoracic fascia in the lower thoracic paravertebral region at the
      T11 level, its spread to the celiac ganglion was examined in fifteen cadavers.
      The dye reached the celiac ganglion in nine cadavers (60%) by passing through the
      retrocrural space, along the greater and lesser splanchnic nerves and through the
      split in the crus of the diaphragm through which the splanchnic nerves traveled.
      In the remaining six cadavers, dye spread toward the ganglion along the crus of
      the diaphragm. In three living subjects the spread of a radio-opaque dye injected
      in the same manner was studied using 3D-computed tomography. This study confirmed
      that the radio-opaque dye traveled toward the celiac ganglion along the crus of
      the diaphragm. From our results we suggest that a fluid communication may exist
      between the lower thoracic paravertebral region and the celiac ganglion in
      cadavers and in living humans and that clinicians should be aware of this
      possible route of spread when administering lower thoracic paravertebral
      anesthesia.

PMID- 12203378
TI  - Brachiocephalic veins: an overlooked approach for central venous catheterization.
AB  - Central venous access is important in both assessment and treatment of the
      patient. In modern clinical practice, a percutaneous approach is preferred. The
      well-established subclavian and internal jugular vein catheterization techniques,
      however, still carry the risk of major acute complications. In this article we
      describe a trial study of a percutaneous brachiocephalic vein catheterization
      technique conducted on a total of 74 cadavers undergoing autopsy. Relying on
      constant and easily recognizable anatomical landmarks, we performed a total of
      128 catheterizations of the right and left brachiocephalic veins. The success of
      catheterization was ascertained by regional dissection. Our results show very
      high reproducibility with a success rate of about 97% on the first attempt of
      catheterization on both right and left sides. Equally important, collateral
      injury of neighboring structures was consistently absent. We propose the
      introduction of this rather overlooked approach into clinical practice.

PMID- 12203379
TI  - Correlation of Web usage and exam performance in a human anatomy and development
      course.
AB  - Course materials for a Human Anatomy and Development Course were placed on the
      World Wide Web (WWW). The materials included a lab manual, lecture notes and
      slides, faculty-generated atlases, Web links, and examinations. The lab manual,
      lecture notes, and atlases were also provided as black-and-white hardcopy. The
      Office of Education assigned students a code name that allowed them to use the
      Web site and take exams anonymously. Student Web use was tracked and correlated
      with their performance on the final examination. Overall use patterns revealed
      that most students used the Web site to prepare for examinations, but not for
      daily studying. Old examinations were the most accessed documents; lecture notes
      were the least accessed. The access patterns of the students with top 20, middle
      20 (closest to the mean), and bottom 20 scores on the final examination were
      compared. In general, there was little difference between the middle and top
      groups. Students in the bottom group used computer resources significantly less
      than the other groups. In a second analysis, the 10 students who used the Web
      site most frequently scored below the mean. The study suggests that interactive
      exercises will be heavily used, but that the preparation of all course materials
      for the WWW may not be an efficient use of institutional resources.

PMID- 12203380
TI  - Giving color to a new curriculum: bodypaint as a tool in medical education.
AB  - We describe a new method, bodypainting, to enhance courses in living anatomy.
      This novel approach was fully integrated in a course that comprised gross
      anatomy, living anatomy, and physical examination of the major abdominal and
      thoracic organs. We designed a course in which the students familiarized
      themselves with the surface markings and subsequently painted the full organ at
      the site of its projection on the body surface. Based on our first experiences,
      we conclude that the course is a successful and enjoyable means of teaching
      various aspects of anatomy in relation to physical examination. This was
      confirmed by an evaluation among the first groups of students.

PMID- 12203381
TI  - Anomalous muscle of the wrist.
AB  - A case of an anomalous muscle found in the right wrist of a 52-year-old man
      during routine carpal tunnel decompression surgery is reported. The muscle was
      observed lying transversely across the carpal tunnel superficial and parallel to
      the flexor retinaculum. Its further definition was subsequently demonstrated by
      postoperative magnetic resonance imaging (MRI). No similar structure was
      detectable on MRI of the left wrist.

PMID- 12203382
TI  - Coexistence of a pectoralis quartus muscle and an unusual axillary arch: case
      report and review.
AB  - A pectoralis quartus muscle and an unusual axillary arch were found on the left
      side of a female cadaver. The axillary arch was a musculoaponeurotic complex
      continuous with the iliacal fibers of the latissimus dorsi. The muscular part,
      together with the tendon of pectoralis major, inserted into the lateral lip of
      the bicipital groove of the humerus, whereas the aponeurotic part was formed by a
      fibrous band that extended deep to the pectoralis major to insert into the
      coracoid process between the attachments of the coracobrachialis and pectoralis
      minor. The pectoralis quartus originated from the rectus sheath, and joined the
      inferior medial border of the fibrous band of the axillary arch, at the lateral
      edge of the pectoralis major. The axillary arch muscle crossed anteriorly the
      axillary vessels and the brachial plexus. The clinical importance of these
      muscles is reviewed.

PMID- 12203383
TI  - Crinis radii: a name for the distal radius.

PMID- 12203384
TI  - Importance of anatomy and dissection: the junior doctor's viewpoint.

PMID- 12203385
TI  - In memoriam: an appreciation of Richard Orkand: 1936-2002.

PMID- 12203386
TI  - Human cortical glial tumors contain neural stem-like cells expressing astroglial
      and neuronal markers in vitro.
AB  - Neural stem cells from neurogenic regions of mammalian CNS are clonogenic in an
      in vitro culture system exploiting serum and anchorage withdrawal in medium
      supplemented with methyl cellulose and the pleiotropic growth factors EGF, FGF2,
      and insulin. The aim of this study was to test whether cortical glial tumors
      contain stem-like cells capable, under this culture system, of forming clones
      showing intraclonal heterogeneity in the expression of neural lineage-specific
      proteins. The high frequencies of clone-forming cells (about 0.1-10 x 10(-3)) in
      clinical tumor specimens with mutated p53, and in neurogenic regions of normal
      human CNS, suggest that the ability to form clones in this culture system is
      induced epigenetically. RT-PCR analyses of populations of normal brain- and tumor
      derived sister clones revealed transcripts for nestin, neuron-specific enolase,
      and glial fibrillary acidic protein (GFAP). However, the tumor-derived clones
      were different from clones derived from neurogenic regions of normal brain in the
      expression of transcripts specific for genes associated with neural cell fate
      determination via the Notch-signaling pathway (Delta and Jagged), and cell
      survival at G2 or mitotic phases (Survivin). Moreover, the individual glioma
      derived clones contain cells immunopositive separately for GFAP or neuronal beta
      III tubulin, as well as single cells coexpressing both glial and neuronal
      markers. The data suggest that the latent critical stem cell characteristics can
      be epigenetically induced by growth conditions not only in cells from neurogenic
      regions of normal CNS but also in cells from cortical glial tumors. Moreover,
      tumor stem-like cells with genetically defective responses to epigenetic stimuli
      may contribute to gliomagenesis and the developmental pathological heterogeneity
      of glial tumors.

PMID- 12203387
TI  - Intracellular chloride modulates A-type potassium currents in astrocytes.
AB  - Application of the GABA(A) receptor agonist muscimol to astrocytes in situ or in
      vitro results in a receptor-mediated Cl(-) current with a concomitant block of
      outward K(+) currents. The effect on K(+) current is largely selective for the
      inactivating A-type current. Parallel experiments with various Cl(-) pipette
      concentrations show a significant reduction in A-type current under low Cl(-)
      conditions with minimal effect on delayed current. In addition, lower Cl(-)
      conditions caused a depolarizing shift of steady-state inactivation (V(1/2), -68
      to -57 mV) and activation (V(1/2), -5.8 to 34 mV) kinetics of A-type current
      only. Cl(-) had no effect on the time course of inactivation or reactivation
      kinetics, suggesting the Cl(-)-mediated effect is largely on activation kinetics,
      indirectly affecting steady-state inactivation. Muscimol application to
      astrocytes under perforated patch control (gramicidin) displayed a similar block
      of A-type current to that of conventional whole cell patch at 40 or 20 mM pipette
      Cl(-) concentrations. With barium application under perforated patch conditions,
      the study of muscimol-mediated Cl(-) current in isolation of the effect on K(+)
      currents was possible. This allowed estimation of intracellular Cl(-)
      concentration from receptor current reversal information. The average
      intracellular Cl(-) concentration was found to be 29 +/- 3.2 mM. The effect on
      activation kinetics and lack of effect on time course of inactivation or
      reactivation suggest that intracellular anion concentrations have an effect on
      the K(+) channel voltage sensor region. Cl(-) may modulate K(+) currents by
      altering membrane field potentials surrounding K(+) channel proteins.

PMID- 12203388
TI  - High-affinity GABA uptake in retinal glial (Muller) cells of the guinea pig:
      electrophysiological characterization, immunohistochemical localization, and
      modeling of efficiency.
AB  - Glial cells may act as important modulators of neuronal information processing,
      in particular, via fast uptake of neuronally released transmitters. Here, we
      characterize the electrogenic gamma-aminobutyric acid (GABA) transporters present
      in the plasma membranes of Muller (glial) cells of the guinea pig retina and
      present an estimate of their functional efficiency. The GABA-evoked whole-cell
      currents are voltage-dependent, with increasing amplitudes and decreasing
      affinity constants at more negative membrane potentials. The transmembranal GABA
      transport is concentration-dependent, with near-maximal currents at 100 microM
      GABA, and is dependent on extracellular sodium and chloride ions; the
      stoichiometry is 1 GABA/2 Na(+)/1 Cl(-). Immunohistochemical labeling and whole
      cell voltage-clamp records reveal that Muller cells express both GAT-1 and GAT-3
      (but not GAT-2), and that the transporter proteins are expressed predominantly at
      plasma membrane sites that, in situ, are localized in the outer retina where GABA
      uptake is performed exclusively by Muller cells. When extracellular GABA enters
      the cell interior, it evokes, via activation of the GABA transaminase, an NAD(P)H
      fluorescence signal selectively in the distal region of the Muller cells where
      their mitochondria are located. Using our experimental data, we simulated the
      GABA clearance from the extracellular space surrounding one Muller cell; these
      estimates show that a pulse of 100 microM extracellular GABA is fully cleared
      after 70 ms. It is suggested that Muller cells may be involved in the regulation
      of GABAergic transmission within the retina by providing a fast termination of
      GABAergic signaling via their highly efficient GABA uptake.

PMID- 12203389
TI  - Remyelination of the spinal cord following intravenous delivery of bone marrow
      cells.
AB  - Bone marrow contains a population of pluripotent cells that can differentiate
      into a variety of cell lineages, including neural cells. When injected directly
      into the demyelinated spinal cord they can elicit remyelination. Recent work has
      shown that following systemic delivery of bone marrow cells functional
      improvement occurs in contusive spinal cord injury and stroke models in rat. We
      report here that secondary to intravenous introduction of an acutely isolated
      bone marrow cell fraction (mononuclear fraction) from adult rat femoral bones
      separated on a density gradient, ultrastructurally defined remyelination occurs
      throughout a focal demyelinated spinal cord lesion. The anatomical pattern of
      remyelination was characteristic of both oligodendrocyte and Schwann cell
      myelination; conduction velocity improved in the remyelinated axons. When the
      injected bone marrow cells were transfected to express LacZ, beta-galactosidase
      reaction product was observed in some myelin-forming cells in the spinal cord.
      Intravenous injection of other myelin-forming cells (Schwann cells and olfactory
      ensheathing cells) or the residual cell fraction of the gradient did not result
      in remyelination, suggesting that remyelination was specific to the delivery of
      the mononuclear fraction. While the precise mechanism of the repair, myelination
      by the bone marrow cells or facilitation of an endogenous repair process, cannot
      be fully determined, the results demonstrate an unprecedented level of myelin
      repair by systemic delivery of the mononuclear cells.

PMID- 12203390
TI  - Inflammatory mediators increase the expression of nociceptin/orphanin FQ in rat
      astrocytes in culture.
AB  - In the central nervous system, glial cells play an important role in inflammatory
      and immune responses, and opioid peptides have been identified as essential
      mediators between the nervous and the immune systems. We report the profound
      upregulation of the opioid-related nociceptin/orphanin FQ (N/OFQ) by inflammatory
      mediators in astrocytes. The bacterial endotoxin, lipopolysaccharide (LPS), and
      the proinflammatory cytokines, interleukin-beta (IL-1beta) and tumor necrosis
      factor-alpha (TNF-alpha), induced levels of N/OFQ mRNA and immunoreactivity. HPLC
      analysis of the immunoreactivity in astrocyte extracts revealed that a large
      molecular weight precursor for N/OFQ is being synthesized and released in
      response to LPS and astrocytes appear to lack the enzymes required to process the
      precursor protein. Western blot analysis showed that LPS treatment elicited the
      activation of ERK 1/2 and p38 MAP kinases. Blockade of the p38 or the ERK MAP
      kinase pathways prevented the LPS-induced increase in N/OFQ mRNA levels
      indicating a role for these cascades in the regulation of N/OFQ genes in response
      to LPS. Regulation of N/OFQ gene expression by ERK and p38 activation may be
      mediated through the transcription factor CREB. We observed CREB phosphorylation
      in response to LPS, which was also prevented by SB202190 and PD98059. The
      NFkappaB pathway also appears to be involved in the induction of N/OFQ
      transcription by LPS, since NFkappaB inhibitors antagonized the effect of LPS on
      N/OFQ expression. Regulation of N/OFQ by inflammatory mediators in astrocytes may
      suggest a role for N/OFQ in neural-glial communication and in inflammatory
      responses in certain neuropathophysiological conditions.

PMID- 12203391
TI  - Mycophenolic acid downregulates inducible nitric oxide synthase induction in
      astrocytes.
AB  - Free radical nitric oxide (NO), generated by inducible nitric oxide synthase
      (iNOS) in astrocytes and macrophages, has been implicated in CNS inflammatory
      disorders such as multiple sclerosis and its animal model experimental autoimmune
      encephalomyelitis (EAE). Mycophenolic acid (MPA), a selective inhibitor of
      inosine monophosphate dehydrogenase (IMPDH), inhibited interferon-gamma (IFN
      gamma) + lipopolysaccharide (LPS)-induced NO production dose-dependently in
      astrocytes, but not in macrophages. The effect of MPA was not mediated through
      interference with IMPDH-dependent synthesis of iNOS cofactor BH4 and subsequent
      suppression of iNOS enzymatic activity, as direct BH4 precursor sepiapterin
      failed to block the action of the drug. However, MPA markedly inhibited IFN-gamma
      + LPS-triggered astrocyte expression of mRNA for iNOS and its transcription
      factor IRF-1, while the expression of tumor necrosis factor-alpha (TNF-alpha)
      gene was not altered. The observed MPA suppression of NO release and iNOS and IRF
      1 induction in astrocytes were efficiently prevented by exogenous guanosine,
      indicating that the drug acted through reduction of IMPDH-dependent synthesis of
      guanosine nucleotides. This IRF-1-dependent inhibition of iNOS activation might
      be partly responsible for the protective effect of MPA in EAE, prompting
      investigation of its potential use in multiple sclerosis.

PMID- 12203392
TI  - Phenotypic analysis of mice deficient in the major myelin protein MOBP, and
      evidence for a novel Mobp isoform.
AB  - Myelin-associated oligodendrocytic basic protein (MOBP) is a recently identified
      major component of central nervous system (CNS) myelin. We previously reported a
      detailed characterization of the genomic region encompassing the Mobp gene,
      elucidating the complex series of transcript splicing responsible for the
      generation of its diverse family of protein isoforms. These basic, positively
      charged polypeptides display spatial and temporal expression patterns consistent
      with a potential role in the compaction and maintenance of the myelin sheath.
      MOBP isoforms have also been localized to the nucleus and the microtubular
      network of oligodendrocytes; transcript corresponding to one isoform is present
      during embryonic development. Recent reports have identified a role for this
      protein family in the pathogenesis of multiple sclerosis, but a clear function
      for the wild-type protein has remained unclear. We report a detailed analysis of
      a targeted mutation of Mobp, which results in the deletion of the translational
      start site and most of the coding sequence of MOBP, and the deletion of the
      entire coding sequence corresponding to a novel, putative MOBP isoform. Our
      analyses clearly demonstrate that MOBP-deficient mice develop normally, generate
      intact compact CNS myelin, and demonstrate no obvious clinical phenotype.
      Furthermore, in contrast with another recent study, we find that Mobp null mice
      demonstrate no significant influence on the axonal diameter of myelinated axons.
      Although MOBP is not essential for myelination, it appears that its absence is
      not simply compensated for by increased expression of the "classic" myelin basic
      protein (MBP).

PMID- 12203393
TI  - Functional melatonin receptors and metabolic coupling in cultured chick
      astrocytes.
AB  - Melatonin is an important hormone regulating circadian clocks in birds, but the
      specific cellular sites of action are not completely known. The present study was
      designed to determine whether astrocytes derived from chick brain contained
      functional melatonin receptors. Primary cell cultures of diencephalon astrocytes
      that express glial fibrillary acidic protein (GFAP), but not neuron-specific
      enolase (NSE) immunoreactivity, were employed to determine the cellular
      distribution and physiological role for the three known receptor subtypes.
      Saturation and Scatchard analysis of 2-[(125)I]iodomelatonin binding demonstrated
      melatonin receptor binding with a high affinity and a pharmacological profile
      similar to that obtained from brain. In situ hybridization for receptor subtypes
      revealed Mel(1A) and Mel(1C) receptor mRNA, but not Mel(1B). Administration of
      pharmacological levels of melatonin acutely inhibited forskolin-stimulated 2
      deoxyglucose (2DG) uptake, while rhythmic administration of physiological levels
      of melatonin gradually imposed a rhythm in 2DG uptake and of the release of both
      lactate and pyruvate into the medium. These results indicate that (1) there are
      functional Mel(1A) and Mel(1C) melatonin receptors in astrocyte-rich cultures,
      and (2) rhythmic administration of melatonin plays an important role in the
      regulation of astrocytic metabolic activity. Together, the data suggest that the
      circadian secretion of melatonin probably plays a role in the global metabolic
      economy of the avian brain through rhythmic regulation of metabolism in
      astrocytes.

PMID- 12203394
TI  - Matrix metalloproteinases in neuroinflammation.
AB  - Matrix metalloproteinases (MMPs) are a gene family of neutral proteases that are
      important in normal development, wound healing, and a wide variety of
      pathological processes, including the spread of metastatic cancer cells,
      arthritic destruction of joints, atherosclerosis, and neuroinflammation. In the
      central nervous system (CNS), MMPs have been shown to degrade components of the
      basal lamina, leading to disruption of the blood-brain barrier (BBB), and to
      contribute to the neuroinflammatory response in many neurological diseases. Brain
      cells express both constitutive and inducible MMPs in response to cellular
      stress. MMPs are tightly regulated to avoid unwanted proteolysis. Secreted as
      inactive enzymes, the MMPs require activation by other proteases and free
      radicals. The MMPs are part of a larger class of metalloproteinases (MPs), which
      includes the recently discovered ADAMs (a disintegrin and metalloproteinase
      domain) and ADAMTS (a disintegrin and metalloproteinase thrombospondin) families.
      MPs have complex roles at the cell surface and within the extracellular matrix.
      At the cell surface, they act as sheddases, releasing growth factors, death
      receptors, and death-inducing ligands, making them important in cell survival and
      death. Tissue inhibitors of metalloproteinases (TIMPs) are endogenous inhibitors
      that regulate the activity of the MMPs. Synthetic inhibitors have been developed
      for the treatment of arthritis and cancer. These hydroxymate-based compounds have
      been shown to reduce injury in experimental allergic encephalomyelitis (EAE),
      experimental allergic neuritis (EAN), cerebral ischemia, intracerebral
      hemorrhage, and viral and bacterial infections. MPs have both beneficial and
      detrimental roles; understanding their expression in various CNS insults will
      allow for the use of MMP inhibitors in the treatment of neurological disorders.

PMID- 12203395
TI  - Kir potassium channel subunit expression in retinal glial cells: implications for
      spatial potassium buffering.
AB  - To understand the role of different K(+) channel subtypes in glial cell-mediated
      spatial buffering of extracellular K(+), immunohistochemical localization of
      inwardly rectifying K(+) channel subunits (Kir2.1, Kir2.2, Kir2.3, Kir4.1, and
      Kir5.1) was performed in the retina of the mouse. Stainings were found for the
      weakly inward-rectifying K(+) channel subunit Kir4.1 and for the strongly inward
      rectifying K(+) channel subunit Kir2.1. The most prominent labeling of the Kir4.1
      protein was found in the endfoot membranes of Muller glial cells facing the
      vitreous body and surrounding retinal blood vessels. Discrete punctate label was
      observed throughout all retinal layers and at the outer limiting membrane. By
      contrast, Kir2.1 immunoreactivity was located predominantly in the membrane
      domains of Muller cells that contact retinal neurons, i.e., along the two stem
      processes, over the soma, and in the side branches extending into the synaptic
      layers. The results suggest a model in which the glial cell-mediated transport of
      extracellular K(+) away from excited neurons is mediated by the cooperation of
      different Kir channel subtypes. Weakly rectifying Kir channels (Kir4.1) are
      expressed predominantly in membrane domains where K(+) currents leave the glial
      cells and enter extracellular "sinks," whereas K(+) influxes from neuronal
      "sources" into glial cells are mediated mainly by strongly rectifying Kir
      channels (Kir 2.1). The expression of strongly rectifying Kir channels along the
      "cables" for spatial buffering currents may prevent an unwarranted outward leak
      of K(+), and, thus, avoid disturbances of neuronal information processing.

PMID- 12203396
TI  - Multiple angiotensin receptor subtypes in normal and tumor astrocytes in vitro.
AB  - A role for neuropeptide receptors in glial tumorigenesis has recently been
      proposed. Although angiotensin receptors are known to mediate proliferative
      effects in many cell types, including brain astrocytes, the possible
      participation of these receptors in glial tumorigenesis remains unknown. In the
      present study, we have examined the expression of the molecularly defined
      angiotensin receptor subtypes AT(1a), AT(1b), and AT(2) in normal perinatal rat
      astrocytes and in a panel of tumor adult astrocytoma cells, using the reverse
      transcriptase-polymerase chain reaction (RT-PCR). Subsequently, we compared the
      mitogenic effect of the angiotensins A(1-8), A(2-8), A(3-8) and the heptapeptide
      "metabolite" A(1-7), on both normal and tumor astrocytes, measured in terms of
      the incorporation of tritiated thymidine. Our results indicate that AT(1a),
      AT(1b), and AT(2) angiotensin receptor mRNA is commonly expressed by many of
      these cells. Of notable exception is the astrocytoma U373 which was not found to
      express AT(1) or AT(2) mRNA. Chronic (24-h) incubation of cells with A(1-8) and
      A(1-7) lead to the induction of mitogenesis, even in the AT(1) and AT(2) mRNA
      negative astrocytoma cell line U373. Moreover, pharmacological analysis indicated
      that the observed mitogenic effects are not mediated by the AT(1) or AT(2) type
      receptors, but rather by a novel, specific A((1-7)) angiotensin receptor, since
      mitogenesis was shown to be partially blocked by the A(1-7) analogue D-Ala(7)A(1
      7) and by the protease inhibitor orthophenanthroline (100 microM). Using Fura-2
      spectrophotometry, we found that activation of this receptor does not alter
      intracellular calcium levels; however, preincubation with the protein kinase
      kinase inhibitor U0126 (10 microM) was found to inhibit these mitogenic effects
      partially. Overall, these results which demonstrate that normal and tumor
      astrocytes express a greater variety of angiotensin receptor subtypes than
      previously thought, support the idea that A(1-7) and its receptor signaling
      system may play an important role in shaping the astrocyte population during
      development. Moreover, the untimely expression of this A((1-7)) receptor may
      represent an important etiological component in the development of brain
      astrocytomas.

PMID- 12203397
TI  - CD38 expression and NAD+-induced intracellular Ca+ mobilization in isolated
      retinal Muller cells.
AB  - Muller cells of the vertebrate retina are prominent radial glia that provide
      essential support to sustain homeostasis of the tissue, including redistribution
      of external potassium, uptake and metabolism of neurotransmitters, and secretion
      of factors that stabilize the retina. Meeting this diversity of functional
      supports requires that Muller cells express numerous receptors, transporters,
      enzymes, and tissue factors. In this study, we provide evidence that adds to the
      dimensions of Muller cell function by demonstrating a unique relationship between
      external NAD(+) and the mobilization of internal calcium, expressed in the form
      of calcium waves. The cellular mechanism that supports internal mobilization of
      calcium appears to depend on a complex multifunctional ectoenzyme, CD38, which
      converts NAD(+) into the intracellular Ca(2+)-mobilizing second-messenger cyclic
      ADP-ribose (cADPR) and could function as a detector for extracellular NAD(+),
      thus providing a novel signal detection system for evaluating the extracellular
      environment. Our results are consistent with a model of intracellular Ca(2+)
      mobilization in which membrane-bound CD38 binds extracellular NAD(+) and triggers
      intracellular Ca(2+) waves either by direct conversion of NAD(+) to cADPR or by
      activating intracellular cADPR synthesis. Our preliminary results indicate that
      the Ca(2+) waves induced by external NAD(+) propagate through an internal pathway
      that depends on the activation of ryanodine receptors, which appear to be
      distributed throughout the Muller cell cytosol. Because NAD(+) is likely to be
      enhanced when cells are stress or damaged, CD38 could enable Muller cells to
      detect NAD(+) under these circumstances and respond appropriately. Alternatively,
      NAD(+) could also represent a novel extracellular, paracrine function that
      mediates signaling between glial cells and/or other cellular elements of the
      retina.

PMID- 12203398
TI  - Y1 receptor of neuropeptide Y as a glial marker in proliferative
      vitreoretinopathy and diseased human retina.
AB  - The Y1 receptor of neuropeptide Y (NPY) has been demonstrated in glial cells of
      astrocytic lineage in vitro. We have studied the immunohistochemical expression
      of Y1 receptors in the glia of the diseased human retina, in tissue samples
      obtained after surgery for proliferative vitreoretinopathy. In this condition,
      glia and other cell types migrate and form epi- or subretinal membranes. Both
      diseased retinas (n = 8) and PVR membranes (n = 43) contained numerous Y1
      immunoreactive cells. In the diseased retina, the Y1 antiserum labeled cells with
      the morphological radial pattern characteristic of Muller cells, whereas in the
      membranes, label appeared in a large population of elongate cells, measuring up
      to 250 microm. In both retina and membranes, double labeling demonstrated that
      the vast majority of Y1-immunoreactive cells were also labeled by a glial
      fibrillary acidic protein (GFAP) antibody, indicating their glial origin. Retinal
      regions devoid of GFAP immunoreactivity also lacked the Y1 label. None of these
      markers was detected in Muller cells of normal retina. Y1 immunoreactivity did
      not co-localize with smooth muscle actin immunoreactivity, a marker of
      myofibroblasts. Expression of Y1 receptors would characterize reactive and
      proliferating glial cells of the diseased retina and could perhaps be involved in
      the proliferation of injured glial cells causing regrowth of PVR membranes and
      the consequent secondary retinal detachments.

PMID- 12203399
TI  - Involvement of cell cycle control in bleomycin-induced mutagen sensitivity.
AB  - Bleomycin-induced chromosomal instability, generally referred to as mutagen
      sensitivity, is associated with an increased risk for the development of
      environmentally related cancer including head and neck squamous cell carcinoma
      and lung cancer. On average, the cultured lymphocytes of patients with these
      types of cancer show an increased number of chromatid breaks per cell after
      bleomycin exposure in the late S or G2 phase of the cell cycle as compared to
      lymphocytes from control persons. The aim of the present study was to investigate
      whether cell cycle regulation is involved in mutagen sensitivity. We determined
      cell cycle arrest after bleomycin-induced DNA damage in 21 lymphoblastoid cell
      lines that varied in mutagen sensitivity score. An ataxia telangiectasia (AT)
      cell line was included for comparison. Using a cut-off point of 0.70 breaks per
      cell, eight cell lines were classified as insensitive and 13 cell lines showed
      the hypersensitive phenotype. Compared to insensitive cell lines, bleomycin
      treated hypersensitive cells remained at a relatively high level of DNA
      synthesis, as measured by thymidine incorporation, and showed a decreased
      accumulation of cells in G2 and M phase, as measured by flow cytometry. AT cells
      showed an extremely high mutagen sensitivity score, a high level of DNA
      synthesis, and a strong G2 block. In conclusion, mutagen sensitivity is
      associated with "damage-resistant growth," which is indicative of impaired cell
      cycle arrest. By which specific pathway(s) this checkpoint defect is explained
      has yet to be elucidated; however, it is probably distinct from the checkpoint
      defect in AT cells. Environ. Mol. Mutagen. 40:79-84, 2002.

PMID- 12203400
TI  - DNA sequence analysis of interlocus recombination between the human T-cell
      receptor gamma variable (GV) and beta diversity-joining (BD/BJ) sequences on
      chromosome 7 (inversion 7).
AB  - V(D)J recombinase-mediated recombination between the T-cell receptor (TCR) gamma
      variable (GV) genes at chromosome 7p15 and the TCR beta joining (BJ) genes at
      7q35 leads to the formation of a hybrid TCR gene. These TCR gamma/beta interlocus
      rearrangements occur at classic V(D)J recombination signal sequences (RSS) and,
      because the loci are in an inverted orientation, result in inversion events that
      are detectable in the chromosome structure as inv(7)(p15;q35). Similar
      rearrangements involving oncogenes and either TCR or immunoglobulin genes
      mediated by the V(D)J recombinase are found in lymphoid malignancies.
      Oligonucleotide primers that allow polymerase chain reaction (PCR) amplification
      across the inv(7) genomic recombination junction sequence have been described.
      Southern blot analysis has been primarily used to confirm the GV/BJ hybrid nature
      of the product, with limited information on the DNA sequence of these
      recombinations. We have modified this PCR method using total genomic DNA from the
      mononuclear cells in peripheral blood samples to increase specificity and to
      allow direct sequencing of the translocation junction that results from the
      recombination between the GV1 and BJ1 families of TCR genes in 25 examples from
      11 individuals (three adults, one child, six newborns, and one ataxia
      telangiectasia (AT) patient). We focused on samples from newborns based on
      previous studies indicating that the predominant hypoxanthine-guanine
      phosphoribosyl transferase (HPRT) mutations in newborns are V(D)J recombinase
      mediated deletion events and that the frequency of these mutations decreases with
      increasing age. Although the dilution series-based PCR assay utilized does not
      yield sharply defined quantitative endpoints, results of this study strongly
      suggest that inv(7) recombinations in newborns occur at equal or lower
      frequencies than those seen in adults. Consistent with the PCR primer pairs, all
      sequenced products contain a GV1 and a BJ1 segment and most also contain a BD1
      segment. GV1s2 and 1s4 were the most frequently found GV1 genes (8 and 9
      examples, respectively) and BJ1s5 and 1s6 were the most frequently found BJ1
      genes (9 and 10 examples, respectively). These results demonstrate the
      effectiveness of this methodology for assessing GV/BJ interlocus rearrangements
      mediated by V(D)J recombinase.

PMID- 12203401
TI  - Removal of benzo(a)pyrene diol epoxide (BPDE)-DNA adducts as a measure of DNA
      repair capacity in lymphoblastoid cell lines from sisters discordant for breast
      cancer.
AB  - The mutagen sensitivity assay is one of the approaches used to investigate
      individual DNA repair capacity. This method is based on the premise that after in
      vitro treatment with a test mutagen, DNA from subjects with defective repair will
      be more damaged than DNA from those with an efficient repair system. However,
      very little is known about unmeasured processes that occur between cell treatment
      and final assessment of DNA damage. To develop a more precise assay, we modified
      the traditional mutagen sensitivity assay to also include measurement of DNA
      damage after culturing cells in the absence of mutagen. First, we treated
      apparently normal and xeroderma pigmentosum lymphoblastoid cell lines with
      various doses of benzo(a)pyrene diol epoxide (BPDE) and harvested cells at
      different time points. A polyclonal antiserum against BPDE-DNA was used to
      quantitate levels of adducts by immunoslot-blot and immunohistochemistry.
      Selected conditions included treatment with 10 microM BPDE, a 4-hr culture in
      mutagen-free medium, and immunohistochemical measurement of BPDE-DNA adducts. The
      method was then applied in a pilot study to 50 lymphoblastoid lines from sisters
      discordant for breast cancer. There was no significant difference between cases
      and controls in the level of BPDE-DNA adducts in lymphoblasts harvested
      immediately after BPDE treatment. However, after a 4-hr culture in mutagen-free
      medium, the level of adducts was significantly higher (P = 0.006) among cases
      than in controls. There was a two-fold increase in mean adduct removal in lines
      from nonaffected as compared to affected sisters (44% and 22% decrease,
      respectively). DNA repair capacity was predictive of case status (P = 0.04) in
      logistic regression analysis. This method, which can be easily applied to large
      numbers of samples, should be useful in studies to investigate the role of DNA
      repair in cancer risk.

PMID- 12203403
TI  - P53 codon 72 polymorphism in coronary artery disease: no evidence for association
      with increased risk or micronucleus frequency.
AB  - A common polymorphism at codon 72 (Arg72Pro) of the p53 gene, a gene which codes
      for a tumor-suppressor protein with both antiproliferative and pro-apoptotic
      actions, has recently been reported to be a risk factor for coronary luminal
      narrowing after angioplasty. However, the association of the polymorphism with
      coronary artery disease (CAD) risk has not been studied. We evaluated the
      distribution of the Arg72Pro genotype in 250 patients, 180 with angiographically
      documented CAD and 70 with normal coronary angiography, by using polymerase chain
      reaction amplification of patient DNA followed by restriction enzyme digestion.
      We also examined the association between the Arg72Pro genotype and chromosome
      damage in 82 male patients (60 CAD and 22 no-CAD) by the micronucleus (MN) test
      in human lymphocytes, a sensitive assay for chromosome breakage and aneuploidy.
      The frequencies of Pro/Pro, Pro/Arg, and Arg/Arg genotypes in CAD patients were
      not significantly different from those who were CAD-free (chi(2) = 0.20, P =
      0.90) and not significantly associated with the extent and severity of CAD. A
      significant increase in MN frequency was observed in relation to smoking status
      (8.4 +/- 0.6, 11.9 +/- 1 and 12.0 +/- 1.6, for non smokers, ex-smokers and
      smokers, respectively; P = 0.02). Moreover, diabetic patients showed higher
      levels of MN than normal patients (13.5 +/- 1.4 vs. 9.6 +/- 0.5, P = 0.0025).
      Also, MN frequency was significantly higher in CAD patients than in no-CAD
      patients (11.2 +/- 0.7 vs. 8.0 +/- 0.9, P = 0.02) and increased with the number
      of affected vessels (9.3 +/- 0.1, 12.2 +/- 1.5 and 12.5 +/- 1.3 for one-, two-,
      and three-vessel disease, respectively; P = 0.02). However, there were no
      associations between MN frequency and the Arg72Pro polymorphism. Although there
      appears to be an association between CAD and MN frequency, our results indicate
      that the Arg72Pro polymorphism does not have a significant impact on CAD or MN
      frequencies.

PMID- 12203402
TI  - Occupational exposure to pesticides and cytogenetic damage: results of a
      Hungarian population study using the micronucleus assay in lymphocytes and buccal
      cells.
AB  - The frequency of micronuclei (MN) in peripheral blood lymphocytes and in buccal
      epithelial cells was used as a biomarker of genotoxic effects resulting from
      occupational exposure to pesticides. In addition, the cytokinesis-block
      proliferation index (CBPI) was calculated to detect possible variations in the
      proliferative kinetics of lymphocytes due to pesticide exposure. This study was
      performed on 84 pesticide-exposed workers and 65 unexposed controls from Hungary.
      The pesticide-exposed workers, classified as moderately and highly exposed, were
      also evaluated separately. Statistical evaluation of the cytogenetic biomarkers
      indicated that there were no significant differences between pesticide-exposed
      workers and controls, nor between moderately and highly exposed workers.
      Nevertheless, the statistical analysis revealed that additional factors such as
      age, sex, ingestion of raw vegetables, and working as a pesticide applicator
      affected lymphocyte MN frequency. In addition, age, sex, and smoking affected the
      frequency of MN in buccal cells. Results from the CBPI analysis showed that the
      proliferation index decreased with pesticide exposure and that this parameter was
      also affected by smoking and by the gender of individuals. The results of this
      study indicate no significant increase in MN in this group of Hungarian workers;
      however, the reduced CBPI in the highly exposed population suggests a possible
      genotoxic effect of pesticide exposure.

PMID- 12203404
TI  - Sex-specific induction of mutations by PhIP in the kidney of male and female rats
      and its modulation by conjugated linoleic acid.
AB  - The heterocyclic amine 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) is
      a recognized mutagen and carcinogen in the colon and prostate of male rats and in
      the mammary gland of female rats. In the current study, we examined the
      mutagenicity of PhIP in the kidney of male and female lacI transgenic rats and
      its modulation by a dietary chemopreventive agent, conjugated linoleic acid
      (CLA). Sex-specific changes in mutation were observed following PhIP and CLA
      treatment. Exposure to 100 ppm PhIP through dietary supplementation for 47 days
      induced a lacI mutation frequency (MF) of 7.7 +/- 0.3 x 10(-5) and 4.7 +/- 1.0 x
      10(-5) in the kidney of male and female rats, respectively. The PhIP-induced MFs
      in the kidney of male and female rats were significantly different from each
      other and were 300% (P < 0.001) and 60% (P < 0.05) higher than the corresponding
      controls, respectively. When rats were given CLA along with PhIP, CLA completely
      inhibited the formation of PhIP-induced mutations in the kidney of female rats,
      but not in male rats. Comparison of mutational spectra did not detect significant
      differences between male rats treated with PhIP and PhIP + CLA. However, unlike
      the -1 frameshifts induced by PhIP in the colon and prostate, which consist
      primarily of G:C deletions, -1 frameshifts in the kidney involved the loss of
      both G:C and A:T basepairs. Our data indicate that the kidney of the rats
      responds in a sex-dependent way to mutagenesis and antimutagenesis by PhIP and
      CLA. These differences may be related to hormonally regulated induction of P450
      enzymes or cell proliferation.

PMID- 12203405
TI  - Two UVC-induced stress response pathways in HeLa cells identified by cDNA
      microarray.
AB  - Environmental toxins induce multiple effects in vivo, involving various molecular
      pathways. The ultraviolet C (UVC, 254 nm) component of sunlight can cause strong
      cytotoxic and genotoxic effects. In this study, UVC-induced stress response
      factors were analyzed by cDNA microarray, using the Millennium(R) Nylon membrane
      chip system. HeLa cells were irradiated with 30 Joule/m(2)/sec UVC, incubated for
      30 or 60 minutes and then subjected to the analysis. Multiple chips were used for
      each experimental condition so that the data could be analyzed statistically.
      Principal component analysis (PCA) was used to identify groups of genes whose
      expression changed in a similar manner with time post-UVC irradiation. Three
      major factors were identified, depending on the directionality of expression
      changes in each gene. The factor loadings in all three identified gene groups
      were high, indicating that genes within each group were highly correlated. Two
      factors exhibited significantly changed expression patterns after 30 minutes of
      incubation but in the opposite direction. This indicates that the "immediate
      early" UVC-induced stress response was elicited by two major pathways.
      Interestingly, expression of the genomic damage-inducible GADD genes, as well as
      p53, was initially decreased, unlike the "immediate early" genes Fos/Jun and Egr
      1, which were strongly increased after 30 minutes of incubation. The results
      indicate that PCA used in the analysis of pre-hypothesized, functionally related
      genes can identify the potential subpathways in a group. This method provides a
      novel approach for identifying functionally-related genes in microarray studies.

PMID- 12203406
TI  - Induction of the SOS response in starved Escherichia coli.
AB  - The SOS system in Escherichia coli is induced in response to DNA damage and the
      arrest of DNA synthesis. Here we show that in AB1157 bacteria starved for
      arginine, conditions for induction of adaptive mutations, the LexA-dependent SOS
      system is induced, but that this occurs only when the bacteria resume growth and
      when the source of carbon is glycerol rather than glucose (glycerol, but not
      glucose, enables synthesis of cAMP). Therefore, we conclude that starved cells
      accumulate some lesions in DNA, which in growth conditions may trigger SOS
      induction by a process that is cAMP-dependent.

PMID- 12203407
TI  - Mammalian cell cytotoxicity and genotoxicity analysis of drinking water
      disinfection by-products.
AB  - Cytotoxicity and genotoxicity assays were used to analyze drinking water
      disinfection by-products (DBPs) in Chinese hamster ovary (CHO) AS52 cells. The
      DBPs were chosen because they are common in drinking water, resulting from
      conventional disinfection using chlorination and chloramination. Data were also
      available to compare these results with cytotoxicity and mutagenicity studies in
      Salmonella typhimurium. The rank order in decreasing chronic cytotoxicity
      measured in a microplate-based assay was bromoacetic acid (BA) >> 3-chloro-4
      (dichloromethyl)-5-hydroxy-2[5H]-furanone (MX) > dibromoacetic acid (DBA) >
      chloroacetic acid (CA) > KBrO(3) > tribromoacetic acid (TBA) > EMS
      (ethylmethanesulfonate, positive control) > dichloroacetic acid (DCA) >
      trichloroacetic acid (TCA). The induction of DNA strand breaks by these agents
      was measured by alkaline single-cell gel electrophoresis (SCGE, comet assay) and
      the rank order in decreasing genotoxicity was BA >> MX > CA > DBA > TBA > EMS >
      KBrO(3), while DCA and TCA were refractory. BA was more cytotoxic (31x) and
      genotoxic (14x) than MX in CHO cells. BA was over 400x more genotoxic than
      potassium bromate. The brominated haloacetic acids (HAAs) were more cytotoxic and
      genotoxic than their chlorinated analogs. The HAAs expressed a statistically
      significant inverse relationship in CHO cell cytotoxicity and genotoxicity as a
      function of increased numbers of halogen atoms per molecule. A quantitative
      comparison was conducted with results from a previous study with cytotoxicity and
      mutagenicity in S. typhimurium. There was no correlation between chronic CHO cell
      and bacterial cell cytotoxicity. DBP-induced CHO cell cytotoxicity was not
      related to mutagenic potency in S. typhimurium. Cytotoxicity in CHO cells was
      statistically significant and highly correlated to CHO cell genotoxicity.
      Finally, we determined that the DBP genotoxic potency in CHO cells and the
      mutagenic potency in S. typhimurium were not related. This suggests that toxicity
      data in S. typhimurium did not quantitatively predict the toxic effects of DBPs
      in mammalian cell systems. The microplate CHO cell cytotoxicity and genotoxicity
      assays were well suited for the analysis of DBPs, especially when the quantity of
      test material is limited.

PMID- 12203408
TI  - O-ethylthymidine adducts are the most relevant damages for mutation induced by N
      ethyl-N-nitrosourea in female germ cells of Drosophila melanogaster.
AB  - Responses to genotoxic agents vary not only among organisms, test systems, and
      cellular stages, but also between sexes; little, however, is known about the
      mutagenic consequences of chemical exposures to female germ cells. In this study,
      the mutagenicity of N-ethyl-N-nitrosourea (ENU) was analyzed in female germ cells
      of Drosophila melanogaster using the recessive-lethal test and the vermilion
      system, which simultaneously generates information on induced mutation frequency
      and mutation spectrum. ENU was mutagenic in all stages of oogenesis, although
      there were differences among the stages. In mature and immature oocytes, ENU
      induced mutations in the vermilion locus were 43.5% A:T-->G:C transitions, 39.1%
      A:T-->T:A transversions, 8.7% G:C-->A:T transitions, and 8.7% A:T-->C:G
      transversions, indicating that the most important premutagenic lesions induced by
      this chemical are O(4)-ethylthymine and O(2)-ethylthymine. The low frequency of
      mutation involving O(6)-ethylguanine (i.e., G:C-->A:T transitions) could be a
      consequence of the repair of these lesions by O(6)-methylguanine DNA
      methyltransferase. Comparison of these results with those previously obtained in
      male germ cells stresses the importance of the repair activity of the analyzed
      cells, because the mutation spectrum in female germ cells was similar to the
      spectrum obtained with repair-proficient spermatogonial cells and different from
      repair-deficient postmeiotic cells. The results also indicate that studies with
      female germ cells could be an alternative to the use of premeiotic male germ
      cells, especially when the analysis of these cells is difficult or almost
      impossible and when studies of in vivo DNA repair in premeiotic germ cells are
      performed.

PMID- 12203413
TI  - From protein domains to drug candidates-natural products as guiding principles in
      the design and synthesis of compound libraries.
AB  - In the continuing effort to find small molecules that alter protein function and
      ultimately might lead to new drugs, combinatorial chemistry has emerged as a very
      powerful tool. Contrary to original expectations that large libraries would
      result in the discovery of many hit and lead structures, it has been recognized
      that the biological relevance, design, and diversity of the library are more
      important. As the universe of conceivable compounds is almost infinite, the
      question arises: where is a biologically validated starting point from which to
      build a combinatorial library? Nature itself might provide an answer: natural
      products have been evolved to bind to proteins. Recent results in structural
      biology and bioinformatics indicate that the number of distinct protein families
      and folds is fairly limited. Often the same structural domain is used by many
      proteins in a more or less modified form created by divergent evolution. Recent
      progress in solid-phase organic synthesis has enabled the synthesis of
      combinatorial libraries based on the structure of complex natural products. It
      can be envisioned that natural-product-based combinatorial synthesis may permit
      hit or lead compounds to be found with enhanced probability and quality.

PMID- 12203414
TI  - Macromolecules containing bipyridine and terpyridine metal complexes: towards
      metallosupramolecular polymers.
AB  - The ability of a broad range of N-heterocycles to act as very effective and
      stable complexation agents for several transition metal ions, such as cobalt(II),
      copper(II), nickel(II), and ruthenium(II), has long been known in analytical
      chemistry. This behavior was later utilized in supramolecular chemistry for the
      construction of highly sophisticated architectures, such as helicates, racks, and
      grids. The discovery of macromolecules by Staudinger in 1922 opened up avenues
      towards sophisticated materials with properties hitherto completely unknown. In
      the last few decades, the combination of macromolecular and supramolecular
      chemistry has been attempted by developing metal-complexing and metal-containing
      polymers for a wide variety of applications that range from filtration to
      catalysis. The stability of the polymer-metal complex is a fundamental
      requirement for such applications. In this respect, the use of bi- and
      terpyridines as chelating ligands is highly promising, since these molecules are
      known to form highly stable complexes with interesting physical properties with
      transition-metal ions. A large number of different structures have been designed
      for many different applications, but polymers based on the application of
      coordinative forces have been prepared in a few cases only. Furthermore, the
      synthetic procedures applied frequently resulted in low yields. During the last
      few years, strong efforts have been made in the direction of self-assembling and
      supramolecular polymers as novel materials with "intelligent" and tunable
      properties. In this review, an overview of this active area at the interface of
      supramolecular and macromolecular chemistry is given.

PMID- 12203415
TI  - Boron chemistry lights the way: optical properties of molecular and polymeric
      systems.
AB  - Electrooptical and electronic materials are the subject of much research
      interest, whereby the focus has often been on electron-rich organic molecules. In
      the past years, new routes to electron-deficient systems have been developed that
      take advantage of the fact that three-coordinate boron is isoelectronic and
      isostructural with a positively charged carbocation, which allows neutral, p-type
      materials to be synthesized directly. This minireview summarizes recent work on
      compounds with 3- and 4-coordinate boron as well as boron clusters, placing it in
      the context of prior studies by the research groups of Williams and Glowgowski,
      Kaim, Lequan, and Marder.

PMID- 12203416
TI  - Enantioselective synthesis of and with allenes.

PMID- 12203417
TI  - Remodeling of gp41-C34 peptide leads to highly effective inhibitors of the fusion
      of HIV-1 with target cells.

PMID- 12203419
TI  - A cluster rearrangement of an open cubane (Cu4Br4) to a prismane (Cu6Br6) in a
      copper(I)-olefin network.

PMID- 12203418
TI  - Structure-function analysis of urotensin II and its use in the construction of a
      ligand-receptor working model.

PMID- 12203420
TI  - Molecular recognition of carbohydrates through directional hydrogen bonds by urea
      appended porphyrins in organic media.

PMID- 12203421
TI  - Micelles and hollow nanospheres based on epsilon-caprolactone-containing polymers
      in aqueous media.

PMID- 12203422
TI  - An efficient and highly enantio- and diastereoselective cyclopropanation of
      olefins catalyzed by Schiff-base ruthenium(II) complexes.

PMID- 12203423
TI  - Supramolecular organization of oligopeptides, through complexation with
      surfactants.

PMID- 12203425
TI  - Copper-catalyzed oxidative heterocyclization by atmospheric oxygen.

PMID- 12203424
TI  - Use of enzymes deactivated by site-directed mutagenesis for the preparation of
      enantioselective membranes.

PMID- 12203426
TI  - Real-time photoacoustic parallel detection of products from catalyst libraries.

PMID- 12203427
TI  - 1,2,3,5-Tetrahydro-1,2,3-methenopentalene, a valence isomer of isoindene:
      synthesis and Diels-Alder reactions.

PMID- 12203428
TI  - Stereoselective synthesis of beta-D-mannopyranosides with reactive mannopyranosyl
      donors possessing a neighboring electron-withdrawing group.

PMID- 12203429
TI  - ULTRA loaded resins based on the cross-linking of linear poly(ethylene imine).
      Improving the atom economy of polymer-supported chemistry.

PMID- 12203430
TI  - A model nucleoside for electron injection into DNA: 5-pyrenyl-2'-deoxyribose.

PMID- 12203431
TI  - Highly selective formation of eight-membered-ring systems by oxidative
      cyclization with molybdenum pentachloride-an environmentally friendly and
      inexpensive access to 2,2'-cyclolignans.

PMID- 12203432
TI  - Rhenium(VII) oxo complexes as extremely active catalysts in the dehydration of
      primary amides and aldoximes to nitriles.

PMID- 12203433
TI  - Lewis acid promoted, O-selective, nucleophilic addition of silyl enol ethers to
      NdoublebondO bonds.

PMID- 12203434
TI  - Chiral templating of silica-lipid lamellar mesophase with helical tubular
      architecture.

PMID- 12203436
TI  - Migration of a phosphane ligand between the two metal centers in diruthenium
      hydrido complexes.

PMID- 12203435
TI  - Aryl CbondH activation by CuII to form an organometallic aryl-CuIII species: a
      novel twist on copper disproportionation.

PMID- 12203437
TI  - A combined effect of molecular electrostatic potential and N7 accessibility
      explains sequence-dependent binding of cis-[Pt(NH3)2(H2O)2]2+ to DNA duplexes.

PMID- 12203438
TI  - Two [Nb6Cl9O3(CN)6]5- isomer anions in two Nb6 cluster oxyhalides:
      Cs5[Nb6Cl9O3(CN)6] x 4 H2O and (Me4N)5[Nb6Cl9O3(CN)6] x 5 H2O.

PMID- 12203439
TI  - Trifluoroacetophenone derivatives as amino acid selective ionophores for the
      potentiometric determination of phenylalanine.

PMID- 12203440
TI  - Combinatorial and rational strategies to develop nonpeptidic alpha4beta7-integrin
      antagonists from cyclic peptides.

PMID- 12203441
TI  - Tetraiodobutatriene: a new cumulenic carbon iodide.

PMID- 12203442
TI  - Atom-transfer tandem radical cyclization reactions promoted by lewis acids.

PMID- 12203443
TI  - Total synthesis of the natural enantiomer of (-)-lepadiformine and determination
      of its absolute stereochemistry.

PMID- 12203444
TI  - "Molecular" molecular sieves: lid-free decamethylcucurbit[5]uril absorbs and
      desorbs gases selectively.

PMID- 12203445
TI  - Efficient and general synthetic approach to pentasubstituted conjugated dienes
      using site-selective coupling of cuprates with 1,4-diiodo-1,3-alkadienes as the
      key reaction.

PMID- 12203446
TI  - Reaction of "[MnII(CH2tBu)2]" with bidentate diimine ligands: from simple base
      adducts to CbondC activation of the ligand.

PMID- 12203447
TI  - Facile oxidation of alcohols to carbonyl compounds using a tris(2
      methylphenyl)bismuth dichloride-DBU binary system.

PMID- 12203448
TI  - Synthesis of cycloalkanones from dienes and allylamines through CbondH and CbondC
      bond activation catalyzed by a rhodium(I) complex.

PMID- 12203449
TI  - An analogue of cymantrene [(eta5-C5H5)Mn(CO)3] that contains a
      dimetalladithiacyclopentadienyl ring.

PMID- 12203450
TI  - Highly enantioselective and practical cinchona-derived phase-transfer catalysts
      for the synthesis of alpha-amino acids.

PMID- 12203451
TI  - Facile syntheses of copper(I) alkynyl clusters stabilized by
      hexafluoroacetylacetonate (hfac) ligands: the structure of [Cu26(hfac)11(1
      pentynyl)15].

PMID- 12203452
TI  - Synthesis and evaluation of transition-state analogue inhibitors of alpha-1,3
      fucosyltransferase.

PMID- 12203453
TI  - Cyanoethynylethenes: a class of powerful electron acceptors for molecular
      scaffolding.

PMID- 12203454
TI  - A structural and functional model of galactose oxidase: control of the one
      electron oxidized active form through two differentiated phenolic arms in a
      tripodal ligand.

PMID- 12203456
TI  - First synthesis of optically pure propargylic N-hydroxylamines by direct, highly
      diastereoselective addition of terminal alkynes to nitrones.

PMID- 12203455
TI  - Experimental detection of the pentaazacyclopentadienide (pentazolate) anion,
      cyclo-N5-**.

PMID- 12203457
TI  - A stoichiometric aromatic CbondH borylation catalyzed by iridium(i)/2,2'
      bipyridine complexes at room temperature.

PMID- 12203458
TI  - Highly enantioselective inverse-electron-demand hetero-diels-alder reactions of
      alpha,beta-unsaturated aldehydes.

PMID- 12203461
TI  - Angewandte weekly--back to the future!

PMID- 12203463
TI  - Approaches to the description and prediction of the binding affinity of small
      molecule ligands to macromolecular receptors.
AB  - The influence of a xenobiotic compound on an organism is usually summarized by
      the expression biological activity. If a controlled, therapeutically relevant,
      and regulatory action is observed the compound has potential as a drug, otherwise
      its toxicity on the biological system is of interest. However, what do we
      understand by the biological activity? In principle, the overall effect on an
      organism has to be considered. However, because of the complexity of the
      interrelated processes involved, as a simplification primarily the "main action"
      on the organism is taken into consideration. On the molecular level, biological
      activity corresponds to the binding of a (low-molecular weight) compound to a
      macromolecular receptor, usually a protein. Enzymatic reactions or signal
      transduction cascades are thereby influenced with respect to their function for
      the organism. We regard this binding as a process under equilibrium conditions;
      thus, binding can be described as an association or dissociation process.
      Accordingly, biological activity is expressed as the affinity of both partners
      for each other, as a thermodynamic equilibrium quantity. How well do we
      understand these terms and how well are they theoretically predictable today? The
      holy grail of rational drug design is the prediction of the biological activity
      of a compound. The processes involving ligand binding are extremely complicated,
      both ligand and protein are flexible molecules, and the energy inventory between
      the bound and unbound states must be considered in aqueous solution. How
      sophisticated and reliable are our experimental approaches to obtaining the
      necessary insight? The present review summarizes our current understanding of the
      binding affinity of a small-molecule ligand to a protein. Both theoretical and
      empirical approaches for predicting binding affinity, starting from the three
      dimensional structure of a protein-ligand complex, will be described and
      compared. Experimental methods, primarily microcalorimetry, will be discussed. As
      a perspective, our own knowledge-based approach towards affinity prediction and
      experimental data on factorizing binding contributions to protein-ligand binding
      will be presented.

PMID- 12203464
TI  - The CP molecule labyrinth: a paradigm of how endeavors in total synthesis lead to
      discoveries and inventions in organic synthesis.
AB  - Imagine an artist carving a sculpture from a marble slab and finding gold nuggets
      in the process. This thought is not a far-fetched description of the work of a
      synthetic chemist pursuing the total synthesis of a natural product. At the end
      of the day, he or she will be judged by the artistry of the final work and the
      weight of the gold discovered in the process. However, as colorful as this
      description of total synthesis may be, it does not entirely capture the essence
      of the endeavor, for there is much more to be told, especially with regard to the
      contrast of frustrating failures and exhilarating moments of discovery. To fully
      appreciate the often Herculean nature of the task and the rewards that accompany
      it, one must sense the details of the enterprise behind the scenes. A more vivid
      description of total synthesis as a struggle against a tough opponent is perhaps
      appropriate to dramatize these elements of the experience. In this article we
      describe one such endeavor of total synthesis which, in addition to reaching the
      target molecule, resulted in a wealth of new synthetic strategies and
      technologies for chemical synthesis. The total synthesis of the CP molecules is
      compared to Theseus' most celebrated athlos (Greek for exploit, accomplishment):
      the conquest of the dreaded Minotaur, which he accomplished through brilliance,
      skill, and bravery having traversed the famous labyrinth with the help of
      Ariadne. This story from Greek mythology comes alive in modern synthetic
      expeditions toward natural products as exemplified by the total synthesis of the
      CP molecules which serve as a paradigm for modern total synthesis endeavors,
      where the objectives are discovery and invention in the broader sense of organic
      synthesis.

PMID- 12203465
TI  - High-performance fibers from spider silk.

PMID- 12203466
TI  - The decaphosphatitanocene dianion--a new chapter in the chemistry of naked
      polyphosphorus ligands.

PMID- 12203467
TI  - Polymorphic forms of rubidium telluride Rb2Te.

PMID- 12203468
TI  - Irreversible adsorption of cellobiose, ascorbic acid, and tyrosine to hydrophobic
      surfaces in water and their separation by molecular stirring.

PMID- 12203469
TI  - Synthesis of neo-peptidoglycans: an unexpected activity of proteases.

PMID- 12203470
TI  - Investigation of reactive intermediates of chemical reactions in solution by
      electrospray ionization mass spectrometry: radical chain reactions.

PMID- 12203471
TI  - 2,3,5,6-Tetrafluorophenylnitren-4-yl: a quartet-ground-state nitrene radical.

PMID- 12203472
TI  - Conversion of hexafluoropropene into 1,1,1-trifluoropropane by rhodium-mediated
      C[bond]F activation.

PMID- 12203473
TI  - Barrier height titration by tunable photoionization combined with chemical
      monitoring: unimolecular keto/enol tautomerization of the acetamide cation
      radical.

PMID- 12203474
TI  - Titanium-promoted stereoselective synthesis of hydroindolones from p-quinamines
      by domino conjugate additions.

PMID- 12203475
TI  - Enantioselective total synthesis of angucyclinone-type antibiotics rubiginones
      A(2) and C(2).

PMID- 12203476
TI  - Carbon-carbon double-bond formation from the reaction of organozinc reagents with
      aldehydes catalyzed by a nickel(II) complex.

PMID- 12203478
TI  - Electrochemical modulation of fluorophore emission on a nanostructured gold film.

PMID- 12203477
TI  - Mechanistic features, cooperativity, and robustness in the self-assembly of
      multicomponent silver(I) grid-type metalloarchitectures.

PMID- 12203479
TI  - Valence-ordering structures and magnetic behavior of metallic MMX chain
      compounds.

PMID- 12203480
TI  - Highly selective transport of organic compounds by using supported liquid
      membranes based on ionic liquids.

PMID- 12203481
TI  - Lewis acid controlled regioselective 1,2 and 1,4 reaction of alpha,beta
      unsaturated carbonyl compounds with Ti(IV) enolates derived from alpha-diazo beta
      keto carbonyl compounds.

PMID- 12203482
TI  - First evidence of fast S[bond]H...S proton transfer in a transition metal
      complex.

PMID- 12203483
TI  - [Ir(4)(CO)(12)]-catalyzed coupling reaction of imidazoles with aldehydes in the
      presence of a hydrosilane to give 2-substituted imidazoles.

PMID- 12203484
TI  - [Lewis acid]+[Co(CO)(4)]- complexes: a versatile class of catalysts for
      carbonylative ring expansion of epoxides and aziridines.

PMID- 12203485
TI  - Remarkably high 1,5-diastereoselectivity in a nickel-catalyzed conjugate addition
      of Me(2)Zn and carbonyl compounds to 1,omega-dienynes with through-space
      coupling.

PMID- 12203486
TI  - Total synthesis of polycephalin C and determination of the absolute
      configurations at the 3",4" ring junction.

PMID- 12203487
TI  - A dendritic porphyrin receptor for C(60) which features a profound positive
      allosteric effect.

PMID- 12203488
TI  - Dinitrogen-bond cleavage in a niobium complex supported by a tridentate aryloxide
      ligand.

PMID- 12203489
TI  - An efficient enantioselective synthesis of (-)-galanthamine.

PMID- 12203491
TI  - Polyoxomolybdenum(V) sulfite complexes: synthesis, structural, and physical
      studies.

PMID- 12203490
TI  - Monomeric compounds containing the cis-[V([double bond]O)(OH)+ core.

PMID- 12203492
TI  - "Molecular symmetry breakers" generating metal-oxide-based nanoobject fragments
      as synthons for complex structures: [[Mo(128)Eu(4)O(388)H(10)(H(2)O)(81)](2)](20
      ), a giant-cluster dimer.

PMID- 12203493
TI  - Mo(V)/pyrophosphate polyoxometalate: an inorganic cryptate.

PMID- 12203494
TI  - A patterned TiO(2)(anatase)/TiO(2)(rutile) bilayer-type photocatalyst: effect of
      the anatase/rutile junction on the photocatalytic activity.

PMID- 12203495
TI  - A breathing ionic crystal displaying selective binding of small alcohols and
      nitriles: K(3)[Cr(3)O(OOCH)(6)(H(2)O)(3)][alpha-SiW(12)O(40)] x 16H(2)O.

PMID- 12203496
TI  - A self-assembled porphyrin box from meso-meso-linked bis[5-p-pyridyl-15-(3,5-di
      octyloxyphenyl)porphyrinato zinc(II)].

PMID- 12203497
TI  - Crystal engineering of a nanoscale Kagome lattice.

PMID- 12203498
TI  - Substrate distortion by a beta-mannanase: snapshots of the Michaelis and covalent
      intermediate complexes suggest a B(2,5) conformation for the transition state.

PMID- 12203499
TI  - The consequences of chirality in crowded arenes--macromolecular helicity,
      hierarchical ordering, and directed assembly.

PMID- 12203500
TI  - C(2)-symmetric chiral pentacyclic guanidine: a phase-transfer catalyst for the
      asymmetric alkylation of tert-butyl glycinate Schiff base.

PMID- 12203501
TI  - Stable non-push-pull phosphanylcarbenes: NMR spectroscopic characterization of a
      methylcarbene.

PMID- 12203502
TI  - Stereoselective pinacol-type rearrangement of 2,3-epoxy alcohols with retention
      of configuration mediated by bis(iodozincio)methane.

PMID- 12203503
TI  - The selective incorporation of alkenes into proteins in Escherichia coli.

PMID- 12203504
TI  - Synthesis and characterization of the neutral "digallene" Ar'GaGaAr' and its
      reduction to Na(2)Ar'GaGaAr' (Ar'=2,6-Dipp(2)C(6)H(3), Dipp=2,6-iPr(2)C(6)H(3)).

PMID- 12203509
TI  - Oxidic nanotubes and nanorods--anisotropic modules for a future nanotechnology.
AB  - The discovery of carbon nanotubes in 1991 is a milestone in nanomaterials
      research. Since then, more and more anisotropic nanoparticles have been detected
      and characterized. The development of nanodevices might benefit from the distinct
      morphology and high aspect ratio of nanorods and nanotubes as these can be
      functionalized in unique ways such as incorporation of nanorods in nanotubes.
      Downscaling a broad range of materials to 1D nanoscopic structures is currently
      the focus of a rapidly growing scientific community. Developing general pathways
      to this goal would transfer a wide variety of properties to the nanoscale-a
      spectrum of phenomena so diverse that it would cover not only inorganic systems
      but all of materials science. Synthesis of real functional materials, however,
      always involves considerable synthetic ingenuity, interdisciplinary
      collaboration, as well as technological and economical realism. The major topic
      of this review is to provide a survey of recent progress in the synthesis of
      oxidic nanotubes and nanorods-with their non-oxidic counterparts briefly
      highlighted-and to outline the major synthetic routes leading to them. With the
      challenges of synthesizing bulk oxidic materials in mind, the establishment of
      trustworthy and uncomplicated ways of providing them as anisotropic nano-modules
      on an industrial scale appears to be more or less serendipity. Of the methods
      utilized in nanotube and nanorod synthesis solvothermal processes have emerged as
      powerful tools for generalizing and systematizing controlled syntheses of nano
      morphologies. The flexibility and reliability of this synthetic approach is
      demonstrated here for the transformation of transition-metal oxides into high
      quality anisotropic nanomaterials.

PMID- 12203510
TI  - Mechanisms of sulfanyl (RS) migrations: synthesis of heterocycles.
AB  - Thiiranium (episulfonium) ions had been acknowledged as reaction intermediates
      for many years, but it was not until 1977 that Nicolaou demonstrated
      systematically that these reactive heterocyclic cations could be trapped by
      carboxylic acids to give lactones. In the years that followed this report,
      extensive research greatly extended the scope of this reaction, particularly with
      regard to the methods for generating thiiranium ions, the types of nucleophiles
      that are compatible with this reaction, and the selectivity involved in the
      cyclization reactions. For many years we have been using thiiranium ions for the
      synthesis of saturated heterocycles. Whereas Nicolaou's method relied on
      electrophilic sulfenylation of alkenes, we have generated thiiranium ions by
      displacement of a leaving group with neighboring-group participation by a
      sulfanyl group. Many of the examples we have reported are of cyclizations that
      are reversible and so where two (and in some cases more) products can result, the
      outcome of the reactions provides fundamental information about the relative
      stability of different heterocyclic ring systems. This Review will begin with a
      brief introduction to sulfanyl participation as a method for generating
      thiiranium (and thiolanium) ions, and will go on to explore the idea of using
      sulfanyl migrations in synthesis. Initially, emphasis will be placed on
      mechanisms of [1,2] sulfanyl migrations: we will look specifically at [1,2]
      sulfanyl migrations (usually PhS) with elimination, substitution, and
      cyclization. Emphasis will then shift to the factors that affect the outcome of
      cyclization reactions. In particular, we will cover cyclizations with hydroxy
      nucleophiles and examine situations in which there are more than one hydroxy
      nucleophile present. We will also examine cyclizations with other nucleophiles,
      namely amines and sulfides. After our discussion of [1,2] sulfanyl migrations, we
      will look very briefly at the scope of [1,4] sulfanyl participation, before
      finally drawing up some guidelines that (we hope) will help other organic
      chemists take advantage of the rearrangement reactions that the sulfanyl group
      has to offer.

PMID- 12203511
TI  - Chemistry in ancient times: the development of blue and purple pigments.

PMID- 12203512
TI  - The diazonamides: the plot thickens.

PMID- 12203513
TI  - Encapsulated lanthanides as luminescent materials.

PMID- 12203514
TI  - Understanding zeolite catalysis: inverse shape selectivity revised.

PMID- 12203515
TI  - Reaction principles and crystal structure design for the topochemical
      polymerization of 1,3-dienes.

PMID- 12203516
TI  - A high nuclearity, mixed-valence manganese(III,IV) complex:
      [Mn21O24(OMe)8(O2CCH2tBu)16(H2O)10].

PMID- 12203517
TI  - Starched carbon nanotubes.

PMID- 12203518
TI  - The first non-heme iron(III) complex with a ligated carboxamido group that
      exhibits photolability of a bound NO ligand.

PMID- 12203519
TI  - Assembly of a truncated-tetrahedral chiral [M12(mu-L)18]24+ cage.

PMID- 12203520
TI  - Luminescence phenomena and solid-state structures of trimethyl- and
      triethylgallium.

PMID- 12203521
TI  - Bridging the gap between polyoxometalates and classic coordination compounds: a
      novel type of hexavanadate complex.

PMID- 12203522
TI  - Benzylic endo-alkylation of phthalan-Cr(CO)3 complexes via temporary silylation:
      an entry to trans-1,3-disubstituted dihydroisobenzofurans.

PMID- 12203523
TI  - Chemically tuning between ferromagnetism and antiferromagnetism by combining
      theory and synthesis in iron/manganese rhodium borides.

PMID- 12203524
TI  - Catalytic activity and poisoning of specific sites on supported metal
      nanoparticles.

PMID- 12203525
TI  - Enantioselective synthesis of propargylamines by copper-catalyzed addition of
      alkynes to enamines.

PMID- 12203526
TI  - Hydrolytic activation of C-F bonds in the gas phase by intrinsically unreactive
      chromium cations.

PMID- 12203527
TI  - Anti-markovnikov hydroamination of terminal alkynes.

PMID- 12203528
TI  - Formation of a butadienenickel-based zwitterionic single-component catalyst for
      ethylene polymerization: an alternative activation pathway for homogeneous
      Ziegler-Natta catalysts of late transition metals.

PMID- 12203530
TI  - Bismuthine BiH3: fact or fiction? High-resolution infrared, millimeter-wave, and
      Ab initio studies.

PMID- 12203529
TI  - Photoactivatable synthetic Ras proteins: "baits" for the identification of plasma
      membrane-bound binding partners of Ras.

PMID- 12203531
TI  - Signal amplification by a fluorescent indicator of a pH-driven intramolecular
      translocation of a copper(II) ion.

PMID- 12203532
TI  - Activation of alkanes upon reaction with PhI(OAc)2-I2.

PMID- 12203533
TI  - Mechanism of the transformation of silica precursor solutions into Si-MFI
      zeolite.

PMID- 12203534
TI  - Synthesis, separation, and characterization of the topoisomers of fused bicyclic
      subphthalocyanine dimers.

PMID- 12203535
TI  - cis and trans Forms of a binuclear subphthalocyanine.

PMID- 12203536
TI  - Synthesis and structure of an azatrisilacyclobutane and its precursor, a novel
      lithium enamide having a tricyclic (LiNSiO)2 skeleton.

PMID- 12203537
TI  - Synthesis, spectroscopy, and solid-state structural characterization of the
      hexanuclear copper macrocycle [Cu6Cl6(mu-PCHP)6].

PMID- 12203538
TI  - Synthesis, structure, and redox properties of diphosphathienoquinones.

PMID- 12203540
TI  - Reaction of 2-butyne with nido-[1,2-(Cp*RuH)2B3H7]: improved kinetic control
      leads to metallacarboranes of novel composition and structure.

PMID- 12203539
TI  - Synthesis and structure of (MeN)Ph2S=C=SPh2(NMe).

PMID- 12203541
TI  - A 1,3,5-triaxial triaminocyclohexane: the triamine corresponding to Kemp's
      triacid.

PMID- 12203542
TI  - Development of a co-mediated rearrangement reaction.

PMID- 12203543
TI  - Rapid phase fluxionality as the determining factor in activity and selectivity of
      highly dispersed, Rh/Al2O3 in deNOx catalysis.

PMID- 12203544
TI  - Morphological control of MCM-41 by pseudomorphic synthesis.

PMID- 12203545
TI  - A cyclodextrin diphosphane as a first and second coordination sphere cavitand:
      evidence for weak C-H...Cl-M hydrogen bonds within metal-capped cavities.

PMID- 12203546
TI  - A stepwise huisgen cycloaddition process: copper(I)-catalyzed regioselective
      "ligation" of azides and terminal alkynes.

PMID- 12203547
TI  - Electronic and steric effects on catalysts for CO2/epoxide polymerization: subtle
      modifications resulting in superior activities.

PMID- 12203548
TI  - A novel polymer-supported arene-ruthenium complex for ring-closing olefin
      metathesis.

PMID- 12203549
TI  - (E)-4-Hydroxy-3-methylbut-2-enyl diphosphate: an intermediate in the formation of
      terpenoids in plant chromoplasts.

PMID- 12203552
TI  - And Huckel was correct after all--a withdrawal and an apology.

PMID- 12203557
TI  - Catalysts for the living insertion polymerization of alkenes: access to new
      polyolefin architectures using Ziegler-Natta chemistry.
AB  - Coordination-insertion polymerization systems have long been superior to their
      anionic, cationic, and radical polymerization counterparts with regard to
      stereochemical control. However, until five years ago, these metal-based
      insertion methods were inferior to ionic and radical mechanisms in the category
      of living polymerization, which is simply a polymerization that occurs with rapid
      initiation and negligible chain termination or transfer. In the last half decade,
      the living insertion polymerization of unactivated olefins has emerged as a
      powerful tool for the synthesis of new polymer architectures. Materials available
      today by this route range from simple homopolymers such as linear and branched
      polyethylene, to atactic or tactic poly(alpha-olefins), to end-functionalized
      polymers and block copolymers. This review article summarizes recent developments
      in this rapidly growing research area at the interface of synthetic and
      mechanistic organometallic chemistry, polymer chemistry, and materials science.
      While special emphasis is placed on polymer properties and novel polymeric
      architectures, most of which were inaccessible just a decade ago, important
      achievements with respect to ligand and catalyst design are also highlighted.

PMID- 12203558
TI  - Chemical strategies for iron acquisition in plants.
AB  - Iron is an essential element for plant nutrition. Although iron is the fourth
      most abundant element (3 %) of the earth's crust, it is not readily available
      because of its low solubility. Therefore, plants need an active mechanism to
      extract iron from the soil. They have evolved several chemical strategies to
      acquire iron ions and the physiology of these mechanisms has been known for a
      long time. Only recently, the use of molecular genetic approaches has led to a
      biochemical and molecular characterization of the players involved, thus
      providing an entry to the manipulation of iron uptake in plants.

PMID- 12203559
TI  - Small interfering RNAs and their chemical synthesis.

PMID- 12203560
TI  - Hydrides and iodides of gold.

PMID- 12203561
TI  - Comment on the communication "highly efficient white organic electroluminescence
      from a double-layer device based on a boron hydroxyphenylpyridine complex" by
      Wang et al.

PMID- 12203563
TI  - The stable pentamethylcyclopentadienyl cation remains unknown.

PMID- 12203565
TI  - Statement.

PMID- 12203564
TI  - Comment on the x-ray structure of pentamethylcyclopentadienyl cation.

PMID- 12203566
TI  - Supramolecular-wire confinement of I2 molecules in channels of the organic
      zeolite tris(o-phenylenedioxy)cyclotriphosphazene.

PMID- 12203567
TI  - Trapping energy from and injecting energy into dye-zeolite nanoantennae.

PMID- 12203568
TI  - Sr(4)N(3): a hitherto missing member in the nitrogen pressure reaction series
      Sr2N-->Sr4N3-->SrN-->SrN2.

PMID- 12203569
TI  - Ones, thiones, and N-oxides: an exercise in imidazole chemistry.

PMID- 12203570
TI  - Tetrafunctional photoaffinity labels based on Nakanishi's m-nitroalkoxy
      substituted phenyltrifluoromethyldiazirine.

PMID- 12203571
TI  - Characterization of a Delta8-sphingolipid desaturase from higher plants: a
      stereochemical and mechanistic study on the origin of E,Z isomers.

PMID- 12203572
TI  - A new type of chainlike tetranuclear rhodium complexes with PR3 and AsMe3 as
      bridging ligands.

PMID- 12203573
TI  - Bifunctional Cp intersection N complexes-unusual structural features and
      electronic coupling in highly preorganized bimetallic systems.

PMID- 12203575
TI  - Synthesis of the dibismuthene complex [[micro-eta2-(cis
      Me(3)SiCH(2)Bi)(2)][W(CO)(5)](2)] from a cyclobismuthane and [W(CO)(5)(thf)].

PMID- 12203574
TI  - Total synthesis of the nematicidal cyclododecapeptide omphalotin A by using
      racemization-free triphosgene-mediated couplings in the solid phase.

PMID- 12203576
TI  - Remarkably large geometry dependence of (57)Fe NMR chemical shifts.

PMID- 12203577
TI  - A triple-decker sandwich complex of barium.

PMID- 12203578
TI  - Ion-pair-mediated asymmetric synthesis of a configurationally stable mononuclear
      tris(diimine)-iron(II) complex.

PMID- 12203579
TI  - Fabricating microarrays of functional proteins using affinity contact printing.

PMID- 12203580
TI  - Au-nanoparticle nanowires based on DNA and polylysine templates.

PMID- 12203581
TI  - A bacterial small-molecule three-hybrid system.

PMID- 12203582
TI  - Proton-induced, reversible evolution of O(2) from the Os(IV)-sulfoximido complex
      [Os(IV)(tpy)(Cl)(2)[NS(O)-3,5-Me(2)C(6)H(3)]].

PMID- 12203583
TI  - A structurally characterized chromium(III) superoxide complex features "side-on"
      bonding.

PMID- 12203584
TI  - Parallels in cation and anion coordination: a new class of cascade complexes.

PMID- 12203585
TI  - Stereoselective formation of quaternary carbon centers: alkylation of alpha,alpha
      disubstituted amide enolates.

PMID- 12203586
TI  - The chemistry of the oxychlorination catalyst: an in situ, time-resolved XANES
      study.

PMID- 12203587
TI  - Comparison of reorganization energies for intra- and intermolecular electron
      transfer.

PMID- 12203588
TI  - Monodentate chiral spiro phosphoramidites: efficient ligands for rhodium
      catalyzed enantioselective hydrogenation of enamides.

PMID- 12203589
TI  - Gas-phase detection of the elusive benzoborirene molecule.

PMID- 12203590
TI  - Arrays of chemomechanically patterned patches of homogeneous and mixed monolayers
      of 1-alkenes and alcohols on single silicon surfaces.

PMID- 12203591
TI  - Synthesis of very thin 1D and 2D CdWO(4) nanoparticles with improved fluorescence
      behavior by polymer-controlled crystallization.

PMID- 12203592
TI  - Synthesis of biologically potent alpha1-->2-linked disaccharide derivatives via
      regioselective one-pot protection-glycosylation.

PMID- 12203593
TI  - Observation of the direct products of migratory insertion in aryl palladium
      carbene complexes and their subsequent hydrolysis.

PMID- 12203594
TI  - Asymmetric baeyer-villiger reaction with hydrogen peroxide catalyzed by a novel
      planar-chiral bisflavin.

PMID- 12203595
TI  - Formation of high-quality CdS and other II-VI semiconductor nanocrystals in
      noncoordinating solvents: tunable reactivity of monomers.

PMID- 12203596
TI  - An umpolung approach to cis-hyponitrite complexes.

PMID- 12203597
TI  - Aminocyclopentadienyl ruthenium chloride: catalytic racemization and dynamic
      kinetic resolution of alcohols at ambient temperature.

PMID- 12203598
TI  - Chiral epoxides by desymmetrizing deprotonation of meso-epoxides.

PMID- 12203599
TI  - Synthesis and structural characterization of organometallic cyclynes: novel
      nanoscale, carbon-rich topologies.

PMID- 12203600
TI  - Hexameric Mg-O stacks with six THF-solvated sodium amide appendages: "super"
      variants of inverse crown ethers generated by cleavage of THF.

PMID- 12203601
TI  - A unique bismuth-iron chain polymer containing the . ..-Bi-Fe-... link: formation
      and structure of [nBuBiFe(CO)(4)](infinity).

PMID- 12203602
TI  - [[Fe(OMe)2[O2CC(OH)Ph2]]12]: synthesis and characterization of a new member in
      the family of molecular ferric wheels with the carboxylatobis(alkoxo) bridging
      unit.

PMID- 12203603
TI  - Poly(p-phenylenephosphaalkene): a pi-conjugated macromolecule containing P=C
      bonds in the main chain.

PMID- 12203604
TI  - A reaction pathway of [Fe(CO)(5)] with alkynes via ferrabicyclobutenones.

PMID- 12203605
TI  - Total synthesis of (+/-)-otteliones A and B.

PMID- 12203606
TI  - [ epsilon-PMo(12)O(36)(OH)(4)[La(H(2)O)(4)](4)](5+): the first epsilon
      PMo(12)O(40) Keggin ion and its association with the two-electron-reduced alpha
      PMo(12)O(40) isomer.

PMID- 12203607
TI  - A new highly efficient ruthenium metathesis catalyst.

PMID- 12203608
TI  - Photochemical sensing of NO(2) with SnO(2) nanoribbon nanosensors at room
      temperature.

PMID- 12203609
TI  - Chirality and macroscopic polar order in a ferroelectric smectic liquid
      crystalline phase formed by achiral polyphilic bent-core molecules.

PMID- 12203613
TI  - Synthesis of Amino[2.2]paracyclophanes-Beneficial Monomers for Bioactive Coating
      of Medical Implant Materials.
AB  - No Abstract

PMID- 12203614
TI  - Quantitative Studies of Binding between Synthetic Galactosyl Ceramide Analogues
      and HIV-1 Gp120 at Planar Membrane Surfaces.
AB  - No Abstract

PMID- 12203615
TI  - N5+: A Novel Homoleptic Polynitrogen Ion as a High Energy Density Material.
AB  - No Abstract

PMID- 12203616
TI  - Twelvefold Functionalization of an Icosahedral Surface by Total Esterification of
      [B12(OH)12]2-: 12(12)-Closomers.
AB  - No Abstract

PMID- 12203617
TI  - Ionization of O3 in Excess N2: A New Route to N2O via Intermediate N2O3+
      Complexes.
AB  - No Abstract

PMID- 12203618
TI  - Alkyl, Silyl, and Phosphane Ligands-Classical Ligands in Nonclassical Bonding
      Modes.
AB  - No Abstract

PMID- 12203619
TI  - In situ IR, NMR, EPR, and UV/Vis Spectroscopy: Tools for New Insight into the
      Mechanisms of Heterogeneous Catalysis.
AB  - The development of new solid catalysts for use in industrial chemistry has
      hitherto been based to a large extent upon the empirical testing of a wide range
      of different materials. In only a few exceptional cases has success been achieved
      in understanding the overall, usually very complex mechanism of the chemical
      reaction through the elucidation of individual intermediate aspects of a
      heterogeneously catalyzed reaction. With the modern approach of combinatorial
      catalysis it is now possible to prepare and test much more rapidly a wide range
      of different materials within a short time and thus find suitable catalysts or
      optimize their chemical composition. Our understanding of the mechanisms of
      reactions catalyzed by these materials must be developed, however, by
      spectroscopic investigations on working catalysts under conditions that are as
      close as possible to practice (temperature, partial pressures of the reactants,
      space velocity). This demands the development and the application of new
      techniques of in situ spectroscopy. This review will show how this objective is
      being achieved. By the term in situ (Lat.: in the original position) is meant the
      investigation of the chemical reactions which are taking place as well as the
      changes in the working catalysts directly in the spectrometer. 

PMID- 12203620
TI  - Ring-opened fullerenes: an unprecedented class of ligands for supramolecular
      chemistry.
AB  - A window of opportunity: With the formation of a large orifice in the C60 core
      (1) and the successful insertion of He and H2 , two critical steps have been
      realized towards the development of an efficient synthetic approach for the
      preparation of endohedral fullerene complexes. 

PMID- 12203621
TI  - 100 years after grignard: where does the organometallic chemistry of the heavy
      alkaline Earth metals stand today?
AB  - Even a century after the discovery of the Grignard reagents, similar compounds of
      the heavy alkaline earth metals are still lacking. Owing to the industrial need
      for such compounds (in particular as anionic polymerization catalysts), the last
      few years have been marked by a rapid, extensive development which has culminated
      in the first structurally characterized alkylbarium derivatives such as the crown
      ether complex of bis(triphenylmethyl)barium (1). hmpt=hexamethylphosphoric acid
      triamide. 

PMID- 12203622
TI  - The Light Shall Show the Way-Or: The Conformational Changes of the Retinal
      Chromophore in Rhodopsin upon Light Activation.
AB  - The visual pigment rhodopsin constitutes the interface between the physical event
      of light absorption and the biochemical process of visual transduction within the
      photoreceptor cells. The signal transduction is initiated by an 11-cis->all-trans
      photoisomerization of the retinal chromophore of rhodopsin which causes a series
      of thermally driven conformational changes of the chromophore and the protein
      moiety. A rhodopsin conformation is generated which allows interaction with a
      heterotrimeric G-protein. Two recent publications follow the chromophore motions
      after light absorption by cross-linking experiments and by solid-state NMR
      spectroscopy. 

PMID- 12203623
TI  - Selective synthesis of novel in and in3 sn nanowires by an organometallic route
      at room temperature.
AB  - Simply decomposing InCp at room temperature in the presence of hexadecylamine
      leads to the formation of indium nanowires with a crystalline bct structure, a
      mean diameter of about 200 nm, and lengths in the micrometer range. The method
      can be extended to the preparation of In3 Sn nanowires of about 100 nm in
      diameter (a transmission electron micrograph is shown in the picture). Cp=C5 H5 (
      ) . 

PMID- 12203624
TI  - [2.2]paracyclophane/dehydrobenzoannulene hybrids: transannular delocalization in
      open-circuited conjugated macrocycles.
AB  - Enhanced global delocalization throughout the "stepped" pi-electron systems of
      the [2.2]paracyclophane/dehydrobenzoannulene (PC/DBA) hybrids 1 and 2 is strongly
      suggested by a comparison of their electronic absorption spectra with those of
      model compounds with complete and interrupted classical aromatic delocalization.
      A distinct bathochromic shift (for 1) and greater absorption intensity at higher
      wavelengths (for 1 and 2) is observed versus the corresponding model
      hydrocarbons. 

PMID- 12203625
TI  - The Remarkable Stable Emerald Green C60 F15 [CBr(CO2 Et)2 ]3 : The First
      [60]Fullerene That Is also the First [18]Trannulene.
AB  - It is both an [18]trannulene and a [60]fullerene. It is aromatic and a hexa
      substituted benzene. It is formed by the first proven example of an SN 2'
      reaction in a fullerene. It is intensely colored and stable. It is C60 F15
      [CBr(CO2 Et)2 ]3 , the first example of a new class of fullerene derivatives (see
      Schlegel diagram). 

PMID- 12203626
TI  - Catalytic Enantioselective Addition of Nitro Compounds to Imines-A Simple
      Approach for the Synthesis of Optically Active beta-Nitro-alpha-Amino Esters.
AB  - The catalytic and asymmetric nitro-Mannich reaction of nitro compounds to alpha
      imino esters catalyzed by chiral bisoxazoline-copper complexes [Eq. (1); Pg =
      protecting group] gave beta-nitro-alpha-amino esters with excellent diastereo-
      and enantioselectivities. The reactions can be performed under ambient
      conditions. 

PMID- 12203627
TI  - Catalytic Asymmetric Direct Mannich Reactions of Carbonyl Compounds with alpha
      Imino Esters.
AB  - The development of a direct catalytic asymmetric Mannich reaction is shown and
      its potential demonstrated by the synthesis of optically active lactones via 4
      hydroxyglutamic acid ester derivatives. The catalytic asymmetric Mannich reaction
      of carbonyl compounds with alpha-imino esters [Eq. (1); Ts = p-toluenesulfonyl]
      gives good yields and diastereoselectivities, as well as excellent
      enantioselectivities. 

PMID- 12203628
TI  - Pentagonal-dodecahedral la2 charge density in [80-ih ]fullerene: la2 @c80.
AB  - A double shell of Platonic solids: A trajectory that connects the six-membered
      rings of Ih -C80 is followed by the two La atoms of La2 @C80 according to maximum
      entropy/Rietveld analysis of the synchrotron powder-diffraction data. The result
      is a pentagonal-dodecahedral charge-density distribution for La2 (brown in the
      picture) inside the icosahedral C80 cage (green). 

PMID- 12203629
TI  - Spontaneous phase transfer of nanoparticulate metals from organic to aqueous
      media.
AB  - 4-dimethylaminopyridine (DMAP) is the answer to the quest for an efficient
      transfer of metallic nanoparticles from organic to aqueous solutions. The picture
      shows the transfer of gold nanoparticles from toluene to water by the addition of
      DMAP (0.1 M, pH 10.5). This method enables the generation of high concentrations
      of nanoparticles with better monodispersity than those commonly prepared in
      water. 

PMID- 12203630
TI  - Membrane-Permeant 3-OH-Phosphorylated Phosphoinositide Derivatives.
AB  - A crucial role in the regulation of epithelial chloride secretion is played by
      the phosphoinositide PtdIns(3,4,5)P3 . Membrane-permeant derivatives of this and
      other naturally occurring phosphoinositides have been synthesized. These
      derivatives, which can be bioactivated, were used in investigations on nasal
      epithelia of patients suffering from cystic fibrosis. 

PMID- 12203631
TI  - Synthesis and spectral characterization of a new class of heterocyclic analogues
      of crystal violet dyes.
AB  - Deep purple: By the transformation of readily available N,N-disubstituted 2
      aminothiophenes and 2-aminothiazoles into heterocyclic analogues of Crystal
      Violet, such as, tris(2-dimethylamino-5-thienyl)methinium prechlorate (cation
      shown), the series of dyes derived from these heterocyclic structural units as
      the important chromophoric component is significantly extended and a gap in the
      class of heteroanalogous triphenylmethane dyes has been closed. 

PMID- 12203632
TI  - A stable DNA duplex containing a non-hydrogen-bonding and non-shape-complementary
      base couple: interstrand stacking as the stability determining factor.
AB  - The stabilizing effect of a dG:dC base-pair can also be imparted to a DNA duplex
      by a non-hydrogen-bonding, non-shape-complementary nucleoside analogue when
      interstrand stacking interactions come into play. This is the case, for example,
      with dBP, which has a bipyridyl (BP) residue as a nucleobase surrogate (the
      picture shows a dBP:dBP pair). 

PMID- 12203633
TI  - Efficient Photooxidative Degradation of Organic Compounds in the Presence of Iron
      Tetrasulfophthalocyanine under Visible Light Irradiation.

PMID- 12203634
TI  - Branched Star-Type Polysilyllithium Compounds: The Effects of beta-Silyl
      Substitution and of Complexation on Their Molecular Structure.
AB  - It was fortunate that the first extended branched polysilyl anion (Me3 SiMe2 Si)3
      Si(-) could be crystallographically characterized in two forms-as the THF complex
      1 and as the dimer 2. Comparison with the analogous (Me3 Si)3 SiLi systems 3 and
      4 shows that beta-Me3 Si substitution and complexation by THF elongate the Si-Li
      distance by 0.09-0.14 A and 0.04-0.07 A, respectively. 

PMID- 12203635
TI  - High molecular mass polyethylene aqueous latexes by catalytic polymerization.
AB  - Semicrystalline microparticles of high molecular mass polyethylene can be
      prepared as aqueous dispersions by catalytic emulsion polymerization of ethylene
      with a mini-emulsified catalyst precursor (D$?rm{?frown}$D=salicylaldimine,
      L=pyridine). Stable polymer latexes are formed. 

PMID- 12203636
TI  - Formal enantioselective Michael addition with umpolung of reactivity.
AB  - By a sequence comprising asymmetric hydroboration, boron-zinc exchange, and
      transmetalation with copper, allylations, alkynylations, and allenylations of
      unsaturated ketals or acetals can be performed with good enantioselectivities
      (see scheme, (-)-IpcBH2 =(-)-isopinocampheylborane, TMS=Me3 Si). The products
      correspond to a formal Michael addition with inversion of polarity. 

PMID- 12203637
TI  - Reversible Tautomeric Transformation between a Bis(amino)cyclodiphosph(V)azene
      and a Bis(imino)cyclodiphosph(V)azane.
AB  - The tautomeric four-membered-ring P-N heterocycles 1, 2, and 3 can be
      interconverted; the formation of the cyclodiphosph(V)azene 1 is enthalpically and
      entropically favored. The crystal structures of the tautomers 1 and 3 have been
      determined and indications are given regarding the mechanism of the
      interconversion. 

PMID- 12203638
TI  - Parallel analysis of the reaction products from combinatorial catalyst libraries.

PMID- 12203639
TI  - Ferromagnetic Ordering in a Diamond-Like Cyano-Bridged Mn(II) Ru(III) Bimetallic
      Coordination Polymer.
AB  - Cyano-mediated interaction of the alternating high-spin Mn(II) centers and low
      spin Ru(III) centers in {Mn[Ru(acac)2 (CN)2 ]2 }n (Hacac=acetylacetone) results
      in long-range ferromagnetic ordering below 3.6 K. This novel Mn(II) Ru(III)
      coordination polymer, which has a diamond-like structure, was constructed from
      [Ru(acac)2 (CN)2 ](-) and Mn(2+) ions. 

PMID- 12203640
TI  - A silyl cation with a three-center si-h-si bond.
AB  - The unusually high kinetic stability of the silyl cation 1 is due to the presence
      of a three-center, two-electron Si-H-Si bond. NMR data ((1) H, (2) H, (13) C,
      (29) Si) are consistent with the static, symmetrical structure shown, which was
      further corroborated by the results of density functional calculations. 

PMID- 12203641
TI  - Formation and Reactivity of the Osmium(IV)-Cyanoimido Complex [Os(IV) (bpy)(Cl)3
      (NCN)](-).
AB  - Oxo-like reactivity exists for a new series of osmium complexes such as [Os(IV)
      (bpy)(Cl)3 (NCN)](-) (bpy=2,2'-bipyridine, see structure) containing the
      cyanoimido ligand. This ligand is formed directly at the metal center by the
      reaction of Os(VI) -nitrido precursors with tetraethylammonium cyanide. In the
      cyanoimido complexes there is an extensive electron-transfer chemistry at the
      metal center and an extensive functional-group chemistry based on the ligand. 

PMID- 12203642
TI  - Ferromagnetic Coupling through Spin Polarization in a Dinuclear Copper(II)
      Metallacyclophane.
AB  - First organic radicals, now metal complexes: A successful extension to metal
      complexes of a well-known organic radical approach to ferromagnetism is
      exemplified by the triplet ground-state molecule containing two Cu(II) centers
      connected by a double m-phenylenediamide skeleton of the cyclophane type shown in
      the scheme. 

PMID- 12203643
TI  - Conjugated complexes composed of quinonediimine and palladium: controlled
      formation of a conjugated trimetallic macrocycle.
AB  - A triangle with a calixarene-like cone configuration: the trimetallamacrocycle
      [{Pd(en)(L)}3 ](6+) (1; L=N,N'-bis(4-dimethylaminophenyl)-1,4
      benzoquinonediimine, en=ethylenediamine; see picture for a space-filling view).
      The coordination array of the redox-active pi-conjugated bridging quinonediimine
      spacer of L and the palladium unit determines whether conjugated 1 or a
      conjugated polymeric complex is formed. 

PMID- 12203644
TI  - Directing topoisomerase I mediated DNA cleavage to specific sites by camptothecin
      tethered to minor- and major-groove ligands.
AB  - The covalent linkage of a hairpin polyamide, which binds in the minor groove, to
      camptothecin provides an efficient system to direct topoisomerase I mediated DNA
      cleavage to specific sites. These conjugates are equally as potent at targeting
      the enzyme to a single site in a DNA fragment as camptothecin conjugates of
      ligands that bind in the major groove (triplex-forming oligonucleotides). 

PMID- 12203645
TI  - Caged thiophosphotyrosine peptides.

PMID- 12203646
TI  - Adhesion Forces between Lewis(X) Determinant Antigens as Measured by Atomic Force
      Microscopy.
AB  - The adhesion forces between individual molecules of Lewis(X) trisaccharide
      antigen (Le(X) ) have been measured in water and in calcium solution by using
      atomic force microscopy (AFM, see graph). These results demonstrate the self
      recognition capability of this antigen, and reinforce the hypothesis that
      carbohydrate-carbohydrate interaction could be considered as the first step in
      the cell-adhesion process in nature. 

PMID- 12203647
TI  - The CH3 N Diradical: Experimental and Theoretical Determinations of the
      Ionization Energies.
AB  - Pyrolysis of CH3 N3 under the protection of NO generates a continuous
      methylnitrene CH3 N diradical beam that enables the ionization energies of
      different ionic states of the CH3 N diradical to be determined by HeI
      photoelectron spectroscopy (PES; see spectrum) and both ab initio and density
      functional theory (DFT) calculations. The ab initio and DFT results are in
      excellent agreement with the PES experiment and show that the CH3 N diradical has
      C3v symmetry and the ground state of the CH3 N radical cation is the (2) E state.

PMID- 12203648
TI  - A Hydrogen-Bonded [(Mercuracarborand-Water)2 -Benzene] pi-Sandwich Complex.
AB  - Two cyclic Lewis acidic receptors, namely B-hexamethyl-9-mecuracarborand-3, [9,12
      (CH3 )2 -C2 B10 H8 Hg]3 , each host a single water molecule. A benzene molecule
      is situated between the two complexed water molecules in a sandwich fashion that
      suggests there is O-H???pi hydrogen bonding. 

PMID- 12203649
TI  - An efficient synthesis of (+/-)-narwedine and (+/-)-galanthamine by an improved
      phenolic oxidative coupling.
AB  - Old problems, new ideas! The biomimetic phenol coupling of norbelladine
      derivatives such as 1 (Bn = benzyl) to form galanthamine (2), a drug used in the
      treatment of Alzheimer's disease, has been greatly improved by the use of the
      hypervalent-iodine oxidation reagent phenyliodine(III) bis(trifluoroacetate)
      (PIFA). 

PMID- 12203650
TI  - Aqueous One-Pot Synthesis of Derivatized Cyclopentadienyl-Tricarbonyl Complexes
      of (99m) Tc with an In Situ CO Source: Application to a Serotonergic Receptor
      Ligand.
AB  - Instant radiopharmaceuticals-just add [(99m) TcO4 ](-) in water! Half-sandwich
      complexes of the type [(RCOCp)(99m) Tc(CO)3 ] (e.g. 1) were synthesized in a
      single step in water from [(99m) TcO4 ](-) . The acidification of the Cp ring by
      a carbonyl substituent and the use of K2 [H3 BCO2 ] as a reducing agent and in
      situ source of CO are instrumental in the synthesis. 

PMID- 12203651
TI  - A chemosensing ensemble for selective carbonate detection in water based on metal
      ligand interactions.
AB  - Displacement of the loosely encapsulated fluorescent indicator coumarine 343 (F)
      from a dicopper(II) cryptate enables the selective fluorimetric detection of the
      HCO3 (-) ion (A) in water (see scheme, *?=Cu(2+) ). The fluorophore is quenched
      when encapsulated, but displays its full emission when released to the solution. 

PMID- 12203652
TI  - Combinatorial templates generated by dip-pen nanolithography for the formation of
      two-dimensional particle arrays.
AB  - Lattices of single polystyrene particles were constructed by using a
      combinatorial approach to analyze particle pattern recognition properties. Dip
      pen nanolithography was used to generate chemical templates of 16
      thiohexadecanoic acid on a gold surface to study the two-dimensional assembly of
      amine- and amidine-modified particles. 

PMID- 12203653
TI  - Orthogonal assembly of nanoparticle building blocks on dip-pen
      nanolithographically generated templates of DNA.
AB  - Nanoscale construction work with DNA: Dip-pen nanolithography (DPN) is used to
      generate nanostructures which can be subsequently functionalized with
      oligonucleotides a' and b' and used to assemble, in an orthogonal manner, gold
      nanoparticles (a, b in scheme) functionalized with sequences complementary to the
      DPN-generated structures. 

PMID- 12203654
TI  - Web Site: An Anchor in the Flood of Data.
AB  - No Abstract

PMID- 12203655
TI  - B-chronic lymphocytic leukemia: practical aspects.
AB  - B-CLL is the most common adult leukemia in the Western world. It is a neoplasia
      of mature looking B-monoclonal lymphocytes co-expressing the CD5 antigen
      (involving the blood, the bone marrow, the lymph nodes and related organs). Much
      new information about the nature of the neoplastic cells, including chromosomal
      and molecular changes as well as mechanisms participating in the survival of the
      leukemic clone have been published recently, in an attempt to elucidate the
      biology of the disease and identify prognostic subgroups. For the time being,
      clinical stage based on Rai and Binet staging systems remains the strongest
      predictor of prognosis and patients' survival, and therefore it affects treatment
      decisions. In the early stages treatment may be delayed until progression. When
      treatment is necessary according to well-established criteria, there are nowadays
      many different options. Chlorambucil has been the standard regimen for many
      years. During the last decade novel modalities have been tried with the emphasis
      on fludarabine and 2-chlorodeoxyadenosine and their combinations with other
      drugs. Such an approach offers greater probability of a durable complete
      remission but no effect on overall survival has been clearly proven so far. Other
      modalities, included in the therapeutic armamentarium, are monoclonal antibodies,
      stem cell transplantation (autologous or allogeneic) and new experimental drugs.
      Supportive care is an important part of patient management and it involves
      restoring hypogammaglobulinemia and disease-related anemia by polyvalent
      immunoglobulin administration and erythropoietin respectively.

PMID- 12203656
TI  - A brief history of pediatric oncology in Porto, Portugal.

PMID- 12203660
TI  - Introduction: managing anemia in pediatric cancer patients.

PMID- 12203661
TI  - Incidence of anemia in pediatric cancer patients in Europe: results of a large,
      international survey.
AB  - BACKGROUND: Anemia occurs frequently in children with cancer, but there is little
      information quantifying the incidence of anemia or treatment. A survey was
      conducted in 1998 in Europe by The Research Partnership with the objective of
      determining the incidence of anemia, identifying the hemoglobin triggers that
      initiated anemia treatment, and the current anemia treatment options available to
      clinicians. PROCEDURE: The survey was conducted in the 10 largest pediatric
      oncology centers each in France, Germany, Italy, Spain, and the UK, and in the 8
      largest centers in both Belgium and The Netherlands. Telephone interviews with
      the most senior physician available in the institution were used to collect data,
      which included the numbers of patients treated or under follow-up, cancer types,
      and treatment practices for anemia. RESULTS: Data were collected for 25,093
      patients. Over 80% of patients were anemic (WHO: hemoglobin <or= 11 g/dL; EORTC:
      hemoglobin <or= 12 g/dL) regardless of tumor type; 97% of patients with leukemia,
      the most prevalent type of cancer (34% of the total population), were anemic.
      Decreases in hemoglobin levels to between 5.5 and 8.0 g/dL were the most common
      factor that precipitated anemia treatment. Treatment was almost exclusively blood
      transfusion; less than 5% of patients received drug treatment (which consisted
      mostly of folic acid or iron). Very few patients received recombinant human
      erythropoietin (rHuEPO, epoetin alfa) to treat anemia. CONCLUSIONS: In general,
      clinicians were not able to give advantages or disadvantages of epoetin alfa as a
      treatment option for treating anemia in children with cancer, which reflects the
      limited knowledge of and experience with this agent.

PMID- 12203662
TI  - Interventions for anemia in pediatric cancer patients.
AB  - BACKGROUND: Children with cancer frequently develop anemia both from the disease
      and from chemo- and radiotherapy. Considered a manageable complication, anemia is
      often not treated until it becomes severe, i.e., hemoglobin (Hb) level <or= 7
      g/dL. The most frequent treatment employed for anemia in children with cancer is
      blood transfusion. PROCEDURE AND RESULTS: A retrospective survey of 74 children
      demonstrated that the use of blood transfusions increased as the intensity of
      therapy increased. At least one blood transfusion was administered to 12.5% of
      children who received standard chemotherapy, and to 59.5% of children who
      received intensive chemotherapy. These data also show that a substantial
      percentage of children did not receive treatment for intensive or high-dose
      chemotherapy, whereas anemia occurred in almost all patients. Recombinant human
      erythropoietin (rHuEPO, epoetin alfa) has been shown to be effective in adults in
      increasing Hb levels and in improving outcomes, including quality of life and
      survival. The use of epoetin alfa in children has not been extensively studied,
      and only a few clinical trials have been conducted. CONCLUSIONS: The good results
      seen in adults, data thus far in pediatrics, and the need for alternatives to
      transfusions in children make epoetin alfa an attractive treatment option for
      anemia in pediatric cancer patients. Clinical studies are underway to evaluate
      the efficacy and safety of epoetin alfa in increasing Hb values and improving
      outcomes in children with cancer.

PMID- 12203663
TI  - Is epoetin alfa a treatment option for chemotherapy-related anemia in children?
AB  - BACKGROUND: The efficacy and safety of epoetin alfa in ameliorating cancer- or
      chemotherapy-related anemia and reducing red blood cell (RBC) transfusion
      requirements have been demonstrated in numerous trials in adult patients.
      However, limited information is available about recombinant human erythropoietin
      (rHuEPO, epoetin alfa) as a treatment option in pediatric cancer patients.
      PROCEDURE: To gain more information about the efficacy and safety of epoetin alfa
      in the treatment of chemotherapy-induced anemia in children with solid tumors
      receiving either platinum- or nonplatinum-containing chemotherapy, an 8-week
      randomized trial was conducted. Epoetin alfa 150 IU/kg was given 3 times a week
      for 8 weeks to 17 patients; 17 control patients received standard of care.
      RESULTS: Transfusions, administered if the hemoglobin (Hb) level dropped to below
      6 g/dL, were necessary for only one patient in the epoetin alfa group, as
      compared with eight patients in the control group (change in Hb from 8.5-10.21
      g/dL in the epoetin alfa group vs. 8.48-8.41 g/dL in the control group).
      CONCLUSIONS: The data from this study suggest that this dosing regimen of epoetin
      alfa is effective and safe in pediatric cancer patients with chemotherapy-related
      anemia. Further studies with epoetin alfa in more children with different
      chemotherapy regimens are needed.

PMID- 12203664
TI  - Early epoetin alfa treatment in children with solid tumors.
AB  - BACKGROUND: Combination chemotherapy is often used for long periods in children
      with solid malignancies, leading to anemia and necessitating intervention with
      red blood cell (RBC) transfusions. Transfusions, however, are associated with a
      variety of adverse events and risks. Recombinant human erythropoietin (rHuEPO,
      epoetin alfa) has been shown to reduce the need for transfusions and to
      ameliorate the symptoms of anemia in adults, but few studies have been conducted
      thus far in pediatric patients. PROCEDURE: Thirty-seven children with solid
      tumors receiving treatment with platinum- or nonplatinum-based chemotherapy were
      treated with epoetin alfa and supplemental iron in a single-center, open-label,
      28-week, case-control study. RESULTS: Epoetin alfa significantly reduced the need
      for RBC (P = 0.007) and platelet (P = 0.01) transfusions, and prolonged the time
      to first RBC transfusion (P = 0.0004) as compared to the control group. Moreover,
      epoetin alfa was effective in maintaining mean hemoglobin levels during the
      course of the study, whereas they declined below baseline after week 9 in the
      control group. CONCLUSIONS: Epoetin alfa is effective and safe in reducing
      transfusion requirements and maintaining adequate hemoglobin levels in children
      with solid tumors undergoing combination chemotherapy.

PMID- 12203666
TI  - What are the challenges in pediatric oncology?

PMID- 12203665
TI  - Recombinant human erythropoietin in pediatric oncology: a review.
AB  - BACKGROUND: Numerous reports on recombinant human erythropoietin (rHuEPO, epoetin
      alfa) treatment of cancer-related anemia in adult patients have been published to
      date. These have shown that epoetin increases hemoglobin levels, significantly
      ameliorates symptoms of anemia, and improves adult patients' quality of life.
      Unfortunately, less is known about the impact of epoetin on anemia in pediatric
      cancer patients. PROCEDURE: It is the objective of this review to summarize and
      analyze data of clinical trials of epoetin treatment of anemia in pediatric
      cancer patients. RESULTS: A total of 15 studies were reviewed; eight were
      considered for detailed analysis and demonstrated important variabilities in
      study methods. Four of the eight were controlled, randomized trials and four were
      open label. CONCLUSIONS: These studies suggested an overall beneficial effect of
      epoetin alfa for treating anemia in children with cancer. Three large,
      multicenter clinical trials of the efficacy and safety of epoetin alfa in anemic
      children with cancer are currently underway, one in Europe and two in North
      America.

PMID- 12203667
TI  - Bright light augments antidepressant effects of medication and wake therapy.
AB  - Inpatient studies have suggested that bright light therapy can be used to sustain
      the antidepressant effects of wake therapy (sleep deprivation). In an outpatient
      trial, a half night of home wake treatment was followed by 1 week of light
      treatment. All subjects had Major Depressive Disorders according to DSM-IV
      criteria and were receiving concomitant antidepressant medication. Subjects were
      randomly assigned to receive either 10,000 lux bright white light for 30 min
      between 6 and 9 AM or dim red (placebo) light at a comparable time. Seven
      subjects completed treatment with bright white light and six completed treatment
      with placebo. On the Hamilton Depression Rating Scale (HDRS17, SIGH-SAD-SR
      version), the group receiving bright light improved 27% in 1 week (P=0.002). The
      group receiving placebo did not improve, except for one outlier. The benefit of
      bright light was significant compared to placebo with removal of the outlier
      (P<0.025).

PMID- 12203668
TI  - Achieving remission with venlafaxine and fluoxetine in major depression: its
      relationship to anxiety symptoms.
AB  - Venlafaxine, a serotonin and norepinephrine reuptake inhibitor (SNRI), produces
      significantly higher remission rates in depressed patients than do the selective
      serotonin reuptake inhibitors (SSRIs). In this analysis of pooled data, we
      explored the relationship between differences in treatment efficacy, early
      improvement of symptoms, and severity of baseline anxiety in depressed patients
      treated with either venlafaxine or fluoxetine. A pooled analysis was performed on
      data from 1,454 outpatients with major depression from five double-blind,
      randomized studies comparing the 6-week efficacy of venlafaxine (542 patients)
      with fluoxetine (555 patients). The Hamilton rating scale for depression (HAM-D)
      total and item scores were analyzed at different treatment times up to 6 weeks.
      Venlafaxine and fluoxetine both produced statistically significant higher
      response and remission rates compared with placebo starting from week 2 for
      response and weeks 3 to 4 for remission. Venlafaxine was statistically
      significantly superior to fluoxetine from week 3 until week 6 in respect of
      response rate, and from week 2 until week 6 for remission rate. After 1 week of
      treatment, greater improvement in individual symptoms was observed in the
      depressed mood, suicide, and psychic anxiety items of the HAM-D scale for both
      venlafaxine- and fluoxetine-treated patients compared with placebo. Improvement
      in psychic anxiety was statistically significantly greater with venlafaxine than
      with fluoxetine. The presence of baseline psychic anxiety correlated
      significantly to treatment outcome when analyzing the remission rates. In
      depressed patients with moderate anxiety (HAM-D psychic anxiety score < or = 2),
      venlafaxine statistically significantly increased remission rates compared with
      placebo from week 4 until week 6, while a significant effect of fluoxetine on
      remission rates was observed starting at week 6. Remission rates in the severely
      anxious depressed patients (score > 2) were statistically significantly higher
      with venlafaxine than placebo starting from week 3 until the end of the study
      period, but no difference could be observed between fluoxetine and placebo.
      Baseline severity of psychic anxiety had a significant impact on remission rates
      after treatment of patients diagnosed with depression. Venlafaxine's superior
      remission rates in the more severely anxious patients and its ability to improve
      psychic anxiety as early as week 1 compared with fluoxetine suggest that
      venlafaxine's early efficacy on anxiety symptoms may be the basis for its
      superior efficacy in depression.

PMID- 12203669
TI  - Circuits and systems in stress. II. Applications to neurobiology and treatment in
      posttraumatic stress disorder.
AB  - This paper follows the preclinical work on the effects of stress on
      neurobiological and neuroendocrine systems and provides a comprehensive working
      model for understanding the pathophysiology of posttraumatic stress disorder
      (PTSD). Studies of the neurobiology of PTSD in clinical populations are reviewed.
      Specific brain areas that play an important role in a variety of types of memory
      are also preferentially affected by stress, including hippocampus, amygdala,
      medial prefrontal cortex, and cingulate. This review indicates the involvement of
      these brain systems in the stress response, and in learning and memory. Affected
      systems in the neural circuitry of PTSD are reviewed (hypothalamic-pituitary
      adrenal axis (HPA-axis), catecholaminergic and serotonergic systems, endogenous
      benzodiazepines, neuropeptides, hypothalamic-pituitary-thyroid axis (HPT-axis),
      and neuro-immunological alterations) as well as changes found with structural and
      functional neuroimaging methods. Converging evidence has emphasized the role of
      early-life trauma in the development of PTSD and other trauma-related disorders.
      Current and new targets for systems that play a role in the neural circuitry of
      PTSD are discussed. This material provides a basis for understanding the
      psychopathology of stress-related disorders, in particular PTSD.

PMID- 12203670
TI  - Depression and Parkinson's disease: a new look at an old problem.
AB  - A National Institutes of Health (National Institute of Neurological Disorders and
      Stroke; National Institute of Mental Health; National Institute on Aging) working
      group meeting focused on the non-motor aspects of Parkinson's disease (PD). Below
      is the summary of the meeting presentations and recommendations for a research
      agenda on the epidemiology, assessment, circuitry, therapeutic approaches, and
      clinical trials of Parkinson's disease co-morbid with depression. A second
      summary will focus on PD and dementia.

PMID- 12203671
TI  - Operation of an academic open access mass spectrometry facility with particular
      reference to the analysis of synthetic compounds.
AB  - Open access mass spectrometry now provides the opportunity to move this
      spectroscopic method to the beginning of the analytical chain, a place formerly
      the exclusive province of NMR and TLC. To date this transition has been occurring
      in industrial settings but there has been less change in the academic
      environment. This paper provides one blueprint for setting up such a facility,
      primarily in support of organic synthesis but also for the use of biological
      scientists. The open access format used at UCI utilizes four instruments: an ESI
      TOFMS system used in the flow injection mode, two GC/MS systems (one in EI and
      one in CI) and a MALDI-TOFMS system. The first three instruments have
      autosamplers and open access software whereas the MALDI system has a fully
      automated plate handling interface. This level of automation allows access to the
      instruments by a user community of more than 100 users, day or night. The
      decisions made in setting up these instruments were based on a 'keep it simple'
      philosophy, given the fact that the primary type of data of interest is the
      molecular mass of the analyte and that data are required for a very wide range of
      structures.

PMID- 12203672
TI  - Interaction of Cu(+) and Cu(2+) ions with alpha-alanine. A density functional
      study.
AB  - The Cu(+) and Cu(2+) preferred binding sites on alpha-alanine and their affinity
      values for this amino acid were determined at the density functional level using
      three different hybrid exchange correlation potentials and the 6-311++G** basis
      set. The results demonstrated that the two ions both give stable complexes with
      alpha-alanine but the stability order of the metalated species and the
      coordination sites are different depending on the nature of the cation. In
      particular, the Cu(+)-alpha-alanine ground-state structure is characterized by an
      eta(2)-N,O coordination with the nitrogen and oxygen atoms belonging to the amino
      and carbonyl groups, respectively. In contrast, the most stable complex of the
      Cu(2+)-alpha-alanine system has an eta(2)-O,O coordination with the cation bonded
      to the -CO(2) (-) moiety of the zwitterionic form of the amino acid. Comparison
      with the Cu(+) and Cu(2+) affinity values for glycine, computed at the same
      levels of theory, demonstrated that the relative values do not change
      significantly as different hybrid functionals are used, although the absolute
      affinities are strongly influenced by the choice of the hybrid potential.

PMID- 12203673
TI  - Isomer separation of hyperbranched polyesteramides with gas-phase H/D exchange
      and a novel MS(n) approach: DoDIP.
AB  - Two approaches are introduced that provide information about the isomeric
      composition of hyperbranched polyesteramides. The first approach is based on a
      novel tandem mass spectrometric (MS(n)) approach that allows the study of
      different types of isomeric structures by a separation based on their difference
      in appearance energy. The method is called DoDIP: dissociation of depleted ion
      populations. A first MS/MS step is used to fragment isomers with relatively low
      appearance energy. The isomers with higher appearance energy are fragmented in a
      second MS/MS step of higher energy. The second approach is based on gas-phase H/D
      exchange experiments that result in a bimodal isotopic distribution for oligomers
      X(n)D(n+1) of which one distribution corresponds to a type of isomeric structure
      that exhibits H/D exchange behaviour and the other to an isomeric structure that
      does not exhibit H/D exchange behaviour. X is a difunctional anhydride of
      phthalic acid (P), 1,2-cyclohexanedicarboxylic acid (C), succinic acid (S) or
      glutaric acid (G). D in X(n)D(n+1) is a trifunctional diisopropanolamine and n
      the degree of polymerization. The type of isomeric structure that does not
      exhibit H/D exchange behaviour has a non-alternating monomer sequence that
      contains an amine bond with a relatively high proton affinity. The other isomeric
      structure that does exhibit H/D exchange behaviour has an alternating monomer
      sequence containing only amide and ester bonds with relatively low proton
      affinity. Oligomer structures were confirmed with additional MS(2) experiments
      after H/D exchange. H/D exchange experiments on the fragments obtained after
      MS(2) of the parent ion show that next to previously postulated mechanisms for
      the cleavage of the ester and amide bond another reaction pathway must be
      operational. A new mechanism is introduced to explain the H/D exchange behaviour
      of the fragments that requires a cleavage of the amide bonds only. Two types of
      fragments are formed by this mechanism. One type is protonated due to the
      cleavage of the amide bond whereas the other type has an oxazolonium ion
      structure due to the loss of an additional H(2)O.

PMID- 12203674
TI  - Tracing glycoprotein structures: electrospray ionization tandem mass
      spectrometric analysis of sugar-peptide adducts.
AB  - Owing to the diversity of carbohydrate structures and their significance for the
      function of many biopolymers, structural analysis of various carbohydrate-related
      compounds is of great importance. Electrospray ionization tandem mass
      spectrometry (ESI-MS/MS) was used to establish the fragmentation behaviour of a
      range of sugar-peptide adducts as model compounds of widespread glycoprotein
      structures. The compounds used in this study were chosen to provide correlation
      of distinct fragment ions with specific structural differences, namely position
      and type of carbohydrate-peptide bond and structure of the sugar moiety. All
      compounds show N- and C-terminal sequence ions along with losses of up to three
      water molecules. Fructose-related Amadori compounds exhibit M + 78 modified N
      terminal peptide fragment ions. Fragmentation of glucose-peptide esters is
      characterized by the sugar ring fragmentation. Additionally, under the ESI-MS
      conditions applied, the esters studied undergo intramolecular reaction giving
      cyclic sugar-peptide structures that can be traced by the presence of N-terminal
      peptide M + 42 adducts. Detailed analysis of cyclic fructose-related compound
      comprising structural features of both studied groups revealed a rich
      fragmentation pattern derived from amino acid residues and water molecules losses
      from [M - 2H(2)O + H](+) ion. Also, some interesting differences were found with
      respect to the nature of carbohydrate moieties.

PMID- 12203675
TI  - Multistep mass spectrometry of heterocyclic amines in a quadrupole ion trap mass
      analyser.
AB  - The fragmentation of heterocyclic amines (HAs) in an ion trap was studied by
      means of the infusion of methanolic solutions containing the compounds under
      assay, and using an atmospheric pressure chemical ionization (APCI) as ion
      source. The MS(n) spectra obtained for compounds included in the same family,
      either aminoimidazoazaarenes (AIAs) or carbolines, were compared in order to
      propose fragmentation pathways for each HA. Moreover, labelled AIAs were used to
      establish the mechanisms. The protonated molecule was always obtained, but
      subsequent fragmentation was different for both families. In the case of AIAs,
      major product ions came from the fragmentation of the aminoimidazole moiety, thus
      the base peak in MS(2) corresponded to the loss of the methyl group, and losses
      of C(2)NH(3) and CN(2)H(2) were also observed. Further fragmentation occurred in
      the heterocyclic rings, mainly with losses of HCN and CH(3)CN. For carbolines,
      the most important product ions came from the loss of ammonia, except for harman
      and norharman, the loss of a methyl group for methylated carbolines or the loss
      of diverse fragments from the heterocyclic rings. In some cases, ion-molecule
      reactions into the ion trap were observed. For instance, for AalphaC or MeAalphaC
      one ion originating from these reactions corresponded to the base peak.

PMID- 12203676
TI  - Lactone enol cation-radicals: gas-phase generation, structure, energetics, and
      reactivity of the ionized enol of butane-4-lactone.
AB  - The cation-radical of 2-hydroxyoxol-2-ene (1(+*)) represents the first lactone
      enol ion whose structure and gas-phase ion chemistry have been studied by
      experiment and theory. Ion 1(+*) was generated by the McLafferty rearrangement in
      ionized 2-acetylbutane-4-lactone and characterized by accurate mass measurements,
      isotope labeling, metastable ion and collisionally activated dissociation (CAD)
      spectra. Metastable 1(+*) undergoes competitive losses of H-4 and CO that show
      interesting deuterium and (13)C isotope effects. The elimination of CO from
      metastable 1(+*) shows a bimodal distribution of kinetic energy release and
      produces (*)CH(2)CH(2)CHdbond;OH(+) (14(+*)) and CH(3)CHdbond;CHOH(+*) (15(+*))
      in ratios which are subject to deuterium isotope effects. Ab initio calculations
      at the G2(MP2) level of theory show that 1(+*) is 105 kJ mol(-1) more stable than
      its oxo form, [butane-4-lactone](+*)(2(+*)). The elimination of CO from 1(+*)
      involves multiple isomerizations by hydrogen migrations and proceeds through ion
      molecule complexes of CO with 14(+*) and 15(+*). In addition, CO is calculated to
      catalyze an exothermic isomerization 14(+*) --> 15(+*) in the ion-molecule
      complexes. Multiple consecutive hydrogen migrations in metastable 1(+*), as
      modeled by RRKM calculations on the G2(MP2) potential energy surface, explain the
      unusual deuterium kinetic isotope effects on the CO elimination.

PMID- 12203677
TI  - Determination of ivermectin B(1a) in animal plasma by liquid chromatography
      combined with electrospray ionization mass spectrometry.
AB  - A novel, sensitive and specific method for the quantitative determination of
      ivermectin B(1a) in animal plasma using liquid chromatography combined with
      positive electrospray ionization tandem mass spectrometry (LC/ESI-MS/MS) is
      presented. Abamectin was used as the internal standard. Extraction of the samples
      was performed with a deproteinization step using acetonitrile. Chromatographic
      separation was achieved on a Nucleosil ODS 5 microm column, using gradient
      elution with 0.2% (v/v) acetic acid in water and 0.2% (v/v) acetic acid in
      acetonitrile. The method was validated according to the requirements defined by
      the European Community. Calibration curves using plasma fortified between 1 and
      100 ng ml(-1) showed a good linear correlation (r > or = 0.9989, goodness-of-fit
      coefficient < or =8.1%). The trueness at 2 and 25 ng ml(-1) (n = 6) was +4.2 and 
      17.1%, respectively. The trueness and between-run precision for the analysis of
      quality control samples at 25 ng ml(-1) was -4.0 and 11.0%, respectively (n =
      16). The limit of quantification of the method was 1.0 ng ml(-1), for which the
      trueness and precision also fell within acceptable limits. Using a signal-to
      noise ratio of 3 : 1, the limit of detection was calculated to be 0.2 ng ml(-1).
      The specificity was demonstrated with respect to ivermectin B(1b). The method was
      successfully used for the quantitative determination of ivermectin B(1a) in
      plasma samples from treated bovines, demonstrating the usefulness of the
      developed method for application in the field of pharmacokinetics.

PMID- 12203678
TI  - Determination of clindamycin in animal plasma by high-performance liquid
      chromatography combined with electrospray ionization mass spectrometry.
AB  - A method for the quantification of clindamycin in animal plasma using high
      performance liquid chromatography combined with electrospray ionization mass
      spectrometry (LC/ESI-MS/MS) is presented. Lincomycin is used as the internal
      standard. The sample preparation includes a simple deproteinization step with
      trichloroacetic acid. Chromatographic separation is achieved on an RP-18 Hypersil
      column using gradient elution with 0.01 M ammonium acetate and acetonitrile as
      mobile phase. Good linearity was observed in the range 0-10 microg ml(-1). The
      limit of quantification of the method is 50 ng ml(-1) and the limit of detection
      is 1.3 ng ml(-1). The method was shown out to be of use for pharmacokinetic
      studies of clindamycin formulations in dogs.

PMID- 12203679
TI  - New results on the dissociative photoionization of CF(4) and CCl(4).
AB  - Using the VIPCO technique, we remeasured and completed the breakdown diagram of
      CCl(4) (+) up to 21 eV energy. The angle-resolved data show both orientation and
      alignment of photoelectrons relative to CX(3) (+) fragments from photoionization
      to the low-lying states of CF(4) (+) and CCl(4) (+). The strength of the
      orientation (forward/backward asymmetry) is surprising in view of the nearly
      spherical symmetry of the parent molecules, and calls for theoretical
      explanation. It may indicate that nuclear and electron motion take place on
      similar time-scales.

PMID- 12203680
TI  - Mass spectrometric identification of in vivo carbamylation of the amino terminus
      of Ectothiorhodospira mobilis high-potential iron-sulfur protein, isozyme 1.
AB  - The complete amino acid sequence of a novel high-potential iron-sulfur protein
      (HiPIP) isozyme 1 from the moderately halophilic phototrophic bacterium
      Ectothiorhodospira mobilis was determined by a combined approach of chemical and
      mass spectrometric sequencing techniques. By mass analysis of the apo- and holo
      protein in the positive electrospray ionization mode using different electrospray
      solvents, the protein was found to be post-translationally modified by a moiety
      of 43 Da. Further analysis showed the nature and location of this modification to
      be a carbamyl group at the N-terminus of the HiPIP. This rare type of
      modification has previously been reported to occur in the water-soluble human
      lens alphaB-crystallin, class D beta-lactamases and some prokaryotic ureases,
      albeit at an internal lysine residue. In this paper, we discuss the mass
      spectrometric features of a carbamylated residue at the N-terminus of a peptide
      or a lysine side-chain during sequence analysis by collision-induced dissociation
      tandem mass spectrometry. Our data provide evidence for the first case of a
      prokaryotic carbamylated electron transport protein occurring in vivo.

PMID- 12203681
TI  - A quantitative model of ultraviolet matrix-assisted laser desorption/ionization.
AB  - A quantitative model of primary ionization in ultraviolet matrix-assisted laser
      desorption/ionization (UV-MALDI) is presented. It includes not only photochemical
      processes such as exciton pooling, but also the effects of the desorption event.
      The interplay of these two is found to be a crucial aspect of the MALDI process.
      The desorbing plume is modeled as an adiabatic expansion with entrained clusters.
      The parameters in the model are defined as much as possible via experiment or by
      analogy with known effects. The model was applied to the matrix 2,5
      dihydroxybenzoic acid and found to reproduce the fluence dependence of the
      fluorescence yield and key features of the picosecond two-pulse ion generation
      efficiency curves. In addition, the model correctly predicts a fluence rather
      than irradiance threshold, the magnitude of the threshold, the magnitude of the
      ion yield, laser wavelength effects, plume temperatures, plume expansion
      velocities and the spot size effect.

PMID- 12203682
TI  - How can EEG/MEG and fMRI/PET data be combined?

PMID- 12203683
TI  - Correspondence of event-related potential tomography and functional magnetic
      resonance imaging during language processing.
AB  - Combining event-related potentials (ERP) and functional magnetic resonance
      imaging (fMRI) may provide sufficient temporal and spatial resolution to clarify
      the functional connectivity of neural processes, provided both methods represent
      the same neural networks. The current study investigates the statistical
      correspondence of ERP tomography and fMRI within the common activity volume and
      time range in a complex visual language task. The results demonstrate that both
      methods represent similar neural networks within the bilateral occipital gyrus,
      lingual gyrus, precuneus and middle frontal gyrus, and the left inferior and
      superior parietal lobe, middle and superior temporal gyrus, cingulate gyrus,
      superior frontal gyrus and precentral gyrus. The mean correspondence of both
      methods over subjects was significant. On an individual basis, only half of the
      subjects showed significantly corresponding activity patterns, suggesting that a
      one-to-one correspondence between individual fMRI activation patterns and ERP
      source tomographies integrated over microstates cannot be assumed in all cases.

PMID- 12203684
TI  - Using larger dimensional signal subspaces to increase sensitivity in fMRI time
      series analyses.
AB  - It has been explained previously how using large dimensional signal-subspaces can
      reduce/eliminate bias in the estimated fMRI response (Burock and Dale [2000]: Hum
      Brain Mapp 11:249-260). It has also been explained how one can project this less
      biased estimate onto a one-dimensional subspace of interest (Burock and Dale
      [2000]: Hum Brain Mapp 11:249-260). In cases where there are multiple, correlated
      characterized response components per event type, separately projecting the full
      hemodynamic response onto one-dimensional subspaces of interest can lead to bias.
      We present an approach for both estimating the full hemodynamic response and
      obtaining from it unbiased estimates of effects of theoretical interest (in the
      context of ordinary least-squares estimation). The latter estimates are identical
      to those obtained by projecting the original data into the space defined by the
      (possibly multi-dimensional) effects of theoretical interest, but the ensuing
      statistical inference can be more sensitive. Hum.

PMID- 12203685
TI  - Odorant differentiated pattern of cerebral activation: comparison of acetone and
      vanillin.
AB  - Whether different odorous compounds (odorants) are processed by different
      cerebral circuits is presently unknown. A first step to address this complicated
      issue is to investigate how the cerebral regions mediating signals from olfactory
      (i.e., unimodal) odorants, differ from those mediating the olfactory + trigeminal
      (i.e., bimodal) odorants. [15O]-H2O-PET scans were conducted in 12 healthy
      females during three separate conditions: birhinal, passive smelling of: 1) the
      unimodal odorant vanillin; 2) the bimodal odorant acetone; and 3) odorless air.
      Significant activations were calculated contrasting vanillin to air, acetone to
      air, and deactivations, running these contrasts in the opposite direction.
      Smelling of vanillin activated bilaterally the amygdala and piriform cortex.
      These regions were only engaged slightly by acetone. Instead, strong activations
      were found in the anterior and central insula and claustrum, the posterior
      portion of anterior cingulate, the somatosensory cortex (SI for face),
      cerebellum, ventral medial (VMPo) and dorsal medial (MDvc) thalamus, the lateral
      hypothalamus, and pons/medulla. In parallel, the somatosensory (SI, below central
      representation of face), secondary visual and auditory cortices, as well as the
      supplementary motor area and the parahippocampal gyri were deactivated. No
      deactivations were observed with vanillin, although the odor components of
      acetone and vanillin were rated similarly intense (75 +/- 17 mm vs. 61 +/- 22 mm,
      NS). The differentiated pattern of cerebral activation during odorant perception
      seems to be dependent on the signal transducing cranial nerves involved. In
      contrast to vanillin, which solely activates the olfactory cortex, acetone
      engages predominantly trigeminal projections from the nasal mucosa. Acetone's
      limited activation of the olfactory cortex may result from a cross-modal
      interaction, with inhibition of acetone's odor component by its trigeminal
      component.

PMID- 12203686
TI  - Carpal tunnel syndrome modifies sensory hand cortical somatotopy: a MEG study.
AB  - The adult somatosensory system has shown reorganizational abilities at cortical
      and subcortical levels after peripheral nerve lesions. In the present study the
      effects of carpal tunnel syndrome (CTS) are investigated as reflected on the
      somatotopy of the primary cortical hand representation. Position and intensity of
      cortical sources activated by the separate electrical stimulation of median nerve
      and Digits 1, 3, and 5 of both affected and non-affected hands are evaluated by
      magnetoencephalographic (MEG) technique. Correlation of MEG results with patient
      , physician- and neurophysiological-oriented evaluations of CTS was carried out.
      Patients showed changes in cortical hand somatotopy in strict relationship to
      self-referred assessment of symptoms and hand disability in daily activities,
      including: 1) a more extended representation of the affected hand when
      paresthesias prevailed; and 2) a more restricted representation due to lateral
      shift of the little finger was observed when pain symptoms dominated the clinical
      picture. Contralateral to the side of CTS, the cortical sources activated by
      Digit 5-stimulation appeared significantly enhanced with respect to contralateral
      ones from non-affected hand. When comparing the amplitude of peripheral sensory
      nerve action potentials of median and ulnar nerves to that of cortical responses
      (i.e., ECD strengths of M20 and M30 components after stimulation of Digits 3 and
      5), a significant selective amplification of M30 with respect to M20 and sensory
      nerve action potential (SNAP) appeared during Digit 3 stimulation compared to
      that observed for Digit 5. This has been interpreted as a central magnification
      mechanism in brain responsiveness, possibly revealing a safety factor enabling
      sensory perception despite the small peripheral signal due to nerve trunk
      dysfunction. Hum.

PMID- 12203687
TI  - Wisconsin Card Sorting Test synchronizes the prefrontal, temporal and posterior
      association cortex in different frequency ranges and extensions.
AB  - Current findings show some brain regions consistently related to performance of
      the Wisconsin Card Sorting Test (WCST). An increase of local cerebral blood flow
      or metabolic demands has been detected in those regions. Functional integration
      of the neuronal circuits that subserve the task performance, based upon the
      identification of the oscillations and their distributed cerebral sources, has
      not been accomplished previously. The event-related tonic oscillations within a
      period of 2,000 msec after the stimulus onset and the probable neural substrate
      were evaluated in healthy volunteers by variable-resolution brain electrical
      tomography (VARETA). The WCST induced a significant increase of delta, theta,
      beta-2, and gamma oscillations, but decrease of alpha. Areas such as the frontal
      subregions, temporal, cingulate, parahippocampal, parietal, occipitotemporal
      cortex, and occipital poles showed modified activity during the task, with EEG
      spectral band selectivity as well as some overlapping among them. Frontal and
      temporal regions generated the delta/theta oscillations. Additionally, the
      occipitotemporal and parietal regions were the source of the delta activity,
      lacking theta activation. The parietal region also showed tonic alpha, beta-2 and
      gamma changes. These data imply that different processes have been simultaneously
      mediated during task performance. Relationships among the individual bands, the
      neural substrata and the specific cognitive process that support the task were
      established. The selectively distributed delta, theta, alpha, beta-2 and gamma
      oscillations reflect communication networks through variable populations of
      neurons, with functional relations to the working memory functions and the
      information processing that subserve the WCST performance.

PMID- 12203688
TI  - Assessment of spatial normalization of whole-brain magnetic resonance images in
      children.
AB  - Commonly used frameworks for spatial normalization of brain imaging data (e.g.,
      Talairach-space) are based on one or more adult brains. As pediatric brains are
      different in size and shape from adult brains and continue to develop through
      childhood, we aimed to assess the influence of age on various spatial
      normalization parameters. One hundred forty-eight healthy children aged 5-18
      years were included in this study. The linear scaling parameters and the
      deformations from the non-linear spatial normalization to both a standard adult
      and a custom pediatric template were analyzed within SPM99. The effect of using a
      brain mask on the linear and of using different levels of constraint on the non
      linear spatial normalization was assessed. Of the linear scaling factors, only
      the X-dimension (left-right) showed a significant age-correlation when based on
      brain tissue, whereas the overall scaling was not correlated with age. When based
      on the whole head, a very strong age-effect can be found in all dimensions. Non
      linear deformations also show localized correlations with age, most pronounced in
      parietal and frontal areas. The total amount of volume change is significantly
      lower when using a pediatric template. It is also substantially influenced by the
      degree of regularization that is exerted on the spatial normalization parameters.
      Our results suggest that in the cortical areas showing a strong correlation of
      deformation with age, caution should be used in assigning imaging results in
      children to a specific morphological structure. Also, to minimize the amount of
      deformation during non-linear spatial normalization, a pediatric template should
      be used. Further implications of our findings on developmental neuroimaging
      studies are discussed.

PMID- 12203689
TI  - Near-infrared spectroscopy can detect brain activity during a color-word matching
      Stroop task in an event-related design.
AB  - Brain activity can be monitored non-invasively by near-infrared spectroscopy
      (NIRS), which has several advantages in comparison with other imaging methods,
      such as flexibility, portability, low cost and biochemical specificity. Moreover,
      patients and children can be repetitively examined. Therefore, the objective of
      the study was to test the feasibility of NIRS for the event-related approach in
      functional brain activation studies with cognitive paradigms. Thus, changes in
      the concentration of oxy-, deoxy-, and total hemoglobin were measured by NIRS in
      14 healthy subjects while performing a color-word matching Stroop task in an
      event-related design. The hemodynamic response (increase in the concentration of
      oxy-/total hemoglobin and decrease in the concentration of deoxy-hemoglobin) was
      stronger during incongruent compared to congruent and neutral trials of the
      Stroop task in the lateral prefrontal cortex bilaterally. This stronger
      hemodynamic response was interpreted as a stronger brain activation during
      incongruent trials of the Stroop task, due to interference. A new method for NIRS
      data evaluation that enables the analysis of the hemodynamic response to each
      single trial is introduced. Each hemodynamic response was characterized by the
      parameters gain, lag and dispersion of a Gaussian function fitted by nonlinear
      regression. Specific differences between the incongruent and neutral condition
      were found for gain and lag. Further, these parameters were correlated with the
      behavioral performance. In conclusion, brain activity may be studied by NIRS
      using cognitive stimuli in an event-related design. Hum. Brain Mapping 17:61-71,
      2002.

PMID- 12203690
TI  - Introduction to olfactory neuroepithelium.
AB  - Among the five senses, the sense of smell (olfaction) is the most sensitive and
      emotional window on the outside world (Stern and Marx, 1999). The olfactory
      system recognizes and discriminates myriad odorants of diverse molecular
      structures. What makes the olfactory system so specific and sensitive? OE
      harboring the olfactory receptor neurons (ORNs) also has an another unusual
      characteristic ability that fascinates scientists. Neurogenesis in this tissue
      continues throughout lifetime. This unique character provides an elegant model to
      study neurogenesis and neuronal plasticity, since neuronal birth,
      differentiation, survival, axon pathfinding, target recognition, synapse
      formation, and cell death can be examined in the mature OE. This special issue of
      Microscopic Research and Technique presents the recent developments in this
      exciting field of neuroscience, "structure and function of olfactory
      neuroepithelium."

PMID- 12203691
TI  - Odor discrimination by G protein-coupled olfactory receptors.
AB  - The vertebrate olfactory system possesses a remarkable capacity to recognize and
      discriminate a variety of odorants by sending the coding information from
      peripheral olfactory sensory neurons in the olfactory epithelium to the olfactory
      bulb of the brain. The recognition of odorants appear to be mediated by a G
      protein-coupled receptor superfamily that consists of approximately 1% of total
      genes in vertebrates. Since the first discovery of the olfactory receptor gene
      superfamily in the rat, similar chemosensory receptors have been found in various
      species across different phyla. The functions of these receptors, however, had
      been uncharacterized until the recently successful functional expression and
      ligand screening of some olfactory receptors in various cell expression systems.
      The functional cloning of odorant receptors from single olfactory neurons allowed
      for the identification of multiple receptors that recognized a particular odorant
      of interest. Reconstitution of the odorant responses demonstrated that odorant
      receptors recognized various structurally-related odorant molecules with a
      specific molecular receptive range, and that odor discrimination is established
      based on a combinatorial receptor code model in which the identities of different
      odorants are encoded by a combination of odorant receptors. The receptor code for
      an odorant changes at different odorant concentrations, consistent with our
      experience that perceived quality of an odorant changes at different
      concentrations. The molecular bases of odor discrimination at the level of
      olfactory receptors appear to correlate well with the receptive field in the
      olfactory bulb where the input signal is further processed to create the specific
      odor maps.

PMID- 12203692
TI  - Cell and molecular biology of human olfaction.
AB  - Progress in our understanding of olfactory receptor physiology has progressed
      greatly over the past 10 years. It has become clear that many anatomical and
      molecular features of the peripheral aspect of the olfactory system have remained
      highly conserved across diverse species. Yet, this structure is responsible for
      conveying a wide variety of information about the environment that is necessary
      to the successful location of food, mates, and avoidance of danger, and it is
      thus not surprising that specializations have also evolved to suit the differing
      needs of different species. While the basic anatomical features reflect those of
      other mammals, functional studies of human olfactory receptor neurons have
      revealed physiological features both similar to and differing from those of other
      mammalian species. This review presents an overview of both the anatomical and
      physiological data describing the cell and molecular biology of the peripheral
      human olfactory system and how it functions in health and disease.

PMID- 12203693
TI  - The electroolfactogram: a review of its history and uses.
AB  - The electroolfactogram (EOG) is a negative electrical potential recorded at the
      surface of the olfactory epithelium of vertebrates. It represents primarily, if
      not exclusively, the summated generator potential in the olfactory receptor
      neurons (ORNs). While a number of studies suggest that secretory or inhibitory
      events may also contribute to the EOG, these are not well established. This
      review outlines (1) the cellular and physiological nature of the EOG response;
      (2) methodological considerations regarding odor selection and delivery, surgical
      preparation, response descriptions, and analysis; and (3) application of the EOG
      in human, fish, and insect olfaction and pheromonal responsivity. A number of
      technical issues associated with EOG recording are also discussed.

PMID- 12203694
TI  - Impulse conduction of olfactory receptor neuron axons.
AB  - Compound action potentials were recorded from rat olfactory receptor neuron axons
      at measured distances from the stimulation electrode along the lateral surface of
      the main olfactory bulb. Distances were plotted as a function of the latencies
      measured from stimulus onset to the prominent negative trough of the triphasic
      compound action potential. A straight line was fitted to these data to calculate
      impulse conduction velocity, 0.42 +/- 0.01 m/s (n = 25). Two procedures were used
      to investigate whether those axons that project to caudal regions of the bulb had
      faster conduction velocities than axons projecting to rostral bulb. First, the
      stimulating electrode was moved to mid-bulb and the recording electrode was
      placed on the caudal bulb. Alternatively, axons were stimulated antidromically at
      the caudal bulb. These two procedures stimulate those axons projecting to caudal
      bulb and bypass olfactory receptor neuron axons that synapse in the rostral bulb.
      The mean impulse conduction velocities from these caudal and antidromic
      recordings were 0.58 +/- 0.19 m/s (n = 8) and 0.57 +/- 0.19 m/s (n = 9),
      respectively. Though both of these means are higher than the impulse conduction
      velocity calculated for stimulation at the rostral bulb, the differences were not
      statistically significant.

PMID- 12203695
TI  - Grouping and representation of odorant receptors in domains of the olfactory bulb
      sensory map.
AB  - Individual glomeruli in the mammalian main olfactory bulb represent a single or
      at most a few types of odorant receptors. Thus the physical arrangement of
      glomeruli at the surface of the olfactory bulb can be viewed as a sensory map
      representing approximately 1,000 types of odorant receptors. This review
      summarizes the recent advance of the knowledge regarding the spatial organization
      of the sensory map in the main olfactory bulb. Recent studies show that
      individual olfactory bulbs contain dual sensory maps, one in the lateral
      hemisphere and the other in the medial hemisphere of the bulb. The tracings of
      selective subsets of olfactory axons to their target glomeruli in the olfactory
      bulb show that glomeruli are parceled into large zones or bands. The spatial
      arrangement of these zones and bands are stereotypical and conserved across
      individual mice. Optical imaging studies show that glomeruli in the most
      rostrodosal zone, zone I, are further parceled into smaller functional domains,
      and suggest that odorant receptors having a common or similar molecular feature
      receptive site are grouped together and represented by glomeruli within the
      functional domain. The possible relation between the functional domain
      organization and the subjectively perceived odor quality (olfactory submodality)
      is reviewed.

PMID- 12203696
TI  - Progenitor cells of the olfactory receptor neuron lineage.
AB  - The olfactory epithelium of the mouse has many properties that make it an ideal
      system for studying the molecular regulation of neurogenesis. We have used a
      combination of in vitro and in vivo approaches to identify three distinct stages
      of neuronal progenitors in the olfactory receptor neuron lineage. The neuronal
      stem cell, which is ultimately responsible for continual neuron renewal in this
      system, gives rise to a transit amplifying progenitor identified by its
      expression of a transcription factor, MASH1. The MASH1-expressing progenitor
      gives rise to a second transit amplifying progenitor, the Immediate Neuronal
      Precursor, which is distinct from the stem cell and MASH1-expressing progenitor,
      and gives rise quantitatively to olfactory receptor neurons. Regulation of
      progenitor cell proliferation and differentiation occurs at each of these three
      cell stages, and growth factors of the fibroblast growth factor (FGF) and bone
      morphogenetic protein (BMP) families appear to play particularly important roles
      in these processes. Analyses of the actions of FGFs and BMPs reveal that negative
      signaling plays at least as important a role as positive signaling in the
      regulation of olfactory neurogenesis.

PMID- 12203697
TI  - Neurotrophins and their receptors in the primary olfactory neuraxis.
AB  - The primary olfactory pathway is an elegant and simple system in which to study
      neurogenesis and neuronal plasticity because of the simple fact that olfactory
      receptor neurons (ORNs) are continually generated throughout the adult lifetimes
      of vertebrates. Thus, neuronal birth, differentiation, survival, axon
      pathfinding, target recognition, synapse formation, and cell death are
      developmental events that can be examined in the mature olfactory epithelium
      (OE). Neurotrophins (nerve growth factor, brain-derived neurotrophic factor, and
      neurotrophin 3, and 4/5) are a family of bioactive peptides that exert their
      effects by interacting with high- and low-affinity receptors on the surfaces of
      responsive cells, and have been implicated in several stages of neuronal
      development throughout the central and peripheral nervous system (CNS and PNS).
      There has been significant interest within the olfactory community as to how
      these multifunctional peptides might regulate the cycle of degeneration and
      regeneration of olfactory receptor neurons. The focus of this review is to
      highlight what is known about the actions of neurotrophins in the primary
      olfactory pathway, and to pinpoint future directions that will enable us to
      further understand their role in olfactory receptor neuron development and
      turnover.

PMID- 12203698
TI  - Role of nerve growth factor in the olfactory system.
AB  - Olfactory neurons are unique in the mammalian nervous system because of their
      capacity to regenerate in adult animals. It has been shown that olfactory
      receptor cells located in the olfactory epithelium are replaced on a continuous
      basis and in response to injury throughout the life span of most species. NGF,
      which is one of the neurotrophic factors, is present in many areas of the central
      and peripheral nervous system. It has been shown that NGF in the olfactory bulb
      plays a role in the survival of cholinergic neurons in the horizontal limb of the
      diagonal band (HDB). Recent studies of NGF in the olfactory bulb suggest that it
      is involved in the development, maintenance, and regeneration of olfactory
      receptor cells. In this study, we review reports examining the relationship
      between NGF in the olfactory bulb and neuronal regeneration and development in
      the mammalian olfactory systems. Low- and high-affinity NGF receptor
      immunoreactivity is markedly expressed during regeneration and at different
      stages of development in the mouse olfactory system. This level of
      immunoreactivity is no longer present after completion of regeneration and at
      maturation. Other findings indicate that NGF injected into the olfactory bulb is
      transported retrogradely to the olfactory epithelium. It has also been shown that
      continuous anti-NGF antibody injection into the olfactory bulb causes
      degeneration and olfactory dysfunction. Administration of NGF directory into
      nasal cavity results in an increase in the expression of olfactory marker protein
      within the olfactory epithelium in axotomized rats. These findings suggested that
      the presence of NGF in the olfactory bulb plays an essential role in
      regeneration, maintenance, and development in the olfactory system of mammals.

PMID- 12203699
TI  - Apoptosis in the mature and developing olfactory neuroepithelium.
AB  - Neuronal apoptosis is important in the developmental sculpting of a normal
      nervous system and also in the loss of neurons caused by neurodegenerative
      disease, ischemia or trauma. In a developing embryo, exquisite mechanisms of
      regulation exist to balance factors that control neuronal birth and death within
      a given neuronal group, so that sufficient neurons develop and survive to elicit
      normal function. Postnatally, the only part of the mammalian nervous system where
      many of these regulatory balance mechanisms are retained is the olfactory
      epithelium (OE). During the last 30 years, researchers investigating olfactory
      receptor neuron cellular and developmental biology have focussed on the
      regeneration of the neuronal population within the olfactory neuroepithelium,
      following the induced death of the mature neuronal population. This body of work
      has thus far overshadowed the equally important and intrinsically linked
      phenomenon of the death of mature olfactory receptor neurons, which is required
      to initiate regeneration. The purpose of this review is to reveal what has been
      established about the different forms of cell death that can occur in neurons of
      the olfactory epithelium, and highlight the identified pro- and anti-apoptotic
      pathways that control the normal and induced turnover of olfactory receptor
      neurons.

PMID- 12203700
TI  - Cellular and molecular biology of ensheathing cells.
AB  - Ensheathing cells are the glial cells that envelop olfactory axons as they course
      from the olfactory epithelium to the bulb. They are derived from the olfactory
      placode and differ from the typical glia in terms of sharing the phenotypes of
      both astrocytes and Schwann cells. The aims of this study are to review (1)
      cellular characterisation of ensheathing cells in vivo and in vitro, (2)
      molecular insight into their growth promoting properties, and (3) their role in
      olfactory development and potential function as a therapeutic agent for nerve
      repair. Much of the characterisation of ensheathing cell property has developed
      from immunohistochemical studies that have been supplemented with new molecular
      methodologies in recent years. Many pieces of evidence clearly indicate that
      ensheathing cells actively produce growth-promoting molecules, which act in a
      paracrine and, in some cases, autocrine manner. However, a review of the
      available literature also suggests that there is a great deal that remains to be
      elucidated regarding the cell biology of ensheathing cells, for example, their
      rate of formation and turnover. In addition, the apparent antigenic heterogeneity
      as revealed by numerous in vitro studies warrants further analysis, particularly
      in view of the fact that in recent years these cells have been touted as a
      possible agent for central nerve repair. New molecular methodologies such as the
      microarray techniques will prove to be crucial for defining the unique
      characteristics of ensheathing cells.

PMID- 12203701
TI  - Recent progress in the neurobiology of the vomeronasal organ.
AB  - In many terrestrial tetrapodes, a pair of vomeronasal organs (VNOs), which are
      chemosensory apparatuses, are situated at the base of the nasal septum in the
      anterior nasal cavity. The purposes of this review are to summarize comparative
      neuroanatomy and to introduce recent progress in neurobiological studies of the
      VNO. Five types of VNOs can be identifiable in terms of anatomical organization;
      snakes possess the most complex one. Sensory cells in the VNO, vomeronasal
      receptor neurons (VRNs), are located in its neuroepithelium, vomeronassal sensory
      epithelium. The VRNs retain the characteristic of epithelial cells in that they
      are born continuously from progenitor cells. They contain two prominent
      subcellular structures: microvilli and extraordinarily large amounts of smooth
      endoplasmic reticulum and a few unique glycoconjugates. The VRNs express two
      types of G-protein -subunits: Gi(alpha2) and Go(alpha) and each of them is
      coupled with putative pheromone receptors, V1Rs and V2Rs, respectively. Recent
      physiological and biochemical studies have demonstrated that pheromones
      depolarize the V1R-Gi(alpha2) and V2R-Go(alpha) VRNs via IP(3)-mediated
      mechanisms. The VRNs do not show adaptation and are ultrasensitive to putative
      pheromones. Other than being a chemosensory organ, the VNO and its primordium
      might play important roles for brain development; hypothalamic neurons that
      produce gonadotropin-releasing hormone are born in the VNO primordium and a few
      other neuron-like cells may be born in the VNO primordium and VNO. In human
      fetuses, anatomical findings strongly suggest that their VNOs contain a
      neuroepithelium. By contrast, it is unlikely that adult human VNO serves as a
      chemosensory organ.

PMID- 12203703
TI  - Introduction to the innervation of bone.

PMID- 12203702
TI  - Pheromone detection by mammalian vomeronasal neurons.
AB  - The vomeronasal organ (VNO) of mammals plays an essential role in the perception
      of chemical stimuli of social nature including pheromone-like signals but direct
      evidence for the transduction of pheromones by vomeronasal sensory neurons has
      been lacking. The recent development of electrophysiological and optical imaging
      methods using confocal microscopy has enabled researchers to systematically
      analyze sensory responses in large populations of mouse vomeronasal neurons.
      These experiments revealed that vomeronasal neurons are surprisingly sensitive
      and highly discriminative detectors of volatile, urinary metabolites that have
      pheromonal activity in recipient mice. Functional mapping studies of pheromone
      receptor activation have uncovered the basic principles of sensory processing by
      vomeronasal neurons and revealed striking differences in the neural mechanisms by
      which chemosensory information is detected by receptor neurons in the VNO and the
      main olfactory epithelium. These advances offer the opportunity to decipher the
      logic of mammalian pheromonal communication.

PMID- 12203704
TI  - Neuronal regulation of bone metabolism and anabolism: calcitonin gene-related
      peptide-, substance P-, and tyrosine hydroxylase-containing nerves and the bone.
AB  - Bone alters its metabolic and anabolic activities in response to the variety of
      systemic and local factors such as hormones and growth factors. Classical
      observations describing abundance of the nerves fibers in bone also predict a
      paradigm that the nervous system influences bone metabolism and anabolism.
      Identification of the nerve-derived signaling molecules, capable of modulating
      cellular activities of the bone cells, facilitates a novel approach to study the
      biology of skeletal innervation. Many of the signaling molecules that may act as
      efferent agents on the bone cells fall into the category of neuropeptides. The
      present article reviews current understanding of the skeletal innervation and
      their proposed physiological effects on bone metabolism, with a special interest
      to calcitonin gene-related peptide (CGRP)-containing nerves fibers. CGRP is
      abundantly distributed in bone via sensory nerves, especially in the epiphyseal
      trabecular bones. Its in vitro actions to the cultured osteoblasts and
      osteoclasts, together with its in vivo localization, strongly support the
      paradigm that the nervous system influences bone metabolism. In addition, CGRP is
      recently shown to be expressed endogenously by the osteoblasts. Transgenic mice
      with osteoblasts overexpressing CGRP are characterized by increased bone
      formation rate and enhanced bone volume, suggesting that CGRP indeed acts on bone
      metabolism not only via nervous route but also via autocrine loop. The current
      article also reviews the distribution of nerve fibers containing substance P
      (SP), another sensory nerve-specific neuropeptide, and tyrosine hydroxylase (TH),
      the rate-limiting enzyme of catecholamine. The distinct effects of SP and
      catecholamines on the bone cells together with their in vivo influences
      manifested by experimental denervation studies suggest that the sensory and
      sympathetic nerves play important roles in bone metabolism.

PMID- 12203705
TI  - Glutamatergic innervation in bone.
AB  - Bone is highly innervated, and evidence for a regulation of bone metabolism by
      nerve fibers has been suggested by many clinical and experimental studies.
      However, the nature of the neuromediators involved in these processes has not
      been well documented. Glutamate (Glu), a major neuromediator of the central
      nervous system (CNS), was recently identified in nerve fibers running in bone
      marrow in close contact with bone cells, suggesting that Glu may also act as a
      neuromediator in this tissue. During the last few years, all the machinery
      required for glutamate signalling in the CNS was demonstrated in bone.
      Osteoblasts and osteoclasts express ionotropic Glu receptors (iGluR) (NMDA, AMPA,
      and Kainate) and metabotropic Glu receptors (mGluR) as well as Glu transporters.
      Electrophysiological studies have demonstrated that NMDA receptors (NMDAR) and
      mGluR are functional on bone cells. NMDAR are involved in osteoclast formation
      and bone resorption and preliminary studies suggest that they may also
      participate in mechanisms underlying osteoblast proliferation or differentiation,
      providing evidence for a direct action of Glu on bone cells. The bone loss
      induced in a model of sciatic neurectomy in growing rats is associated with a
      decrease of glutamatergic innervation, suggesting that Glu released by nerve
      fibers may contribute to the regulation of bone remodeling. The manipulation of
      Glu action in bone may, therefore, represent a new therapeutic target for
      pathologies associated with modifications of bone remodeling.

PMID- 12203706
TI  - Adrenergic regulation of bone metabolism: possible involvement of sympathetic
      innervation of osteoblastic and osteoclastic cells.
AB  - It has been demonstrated that human osteoblastic as well as osteoclastic cells
      are equipped with adrenergic receptors and neuropeptide receptors and that they
      constitutively express diffusible axon guidance molecules that are known to
      function as a chemoattractant and/or chemorepellent for growing nerve fibers.
      These findings suggest that the extension of axons of sympathetic and peripheral
      sensory neurons to osteoblastic and osteoclastic cells is required for the
      dynamic neural regulation of local bone metabolism. Recently, bone resorption
      modulated by sympathetic stimulation was demonstrated to be associated with ODF
      (osteoclast differentiation factor) and OCIF (osteoclastogenesis inhibitory
      factor) produced by osteoblasts/stromal cells. This review summarizes the
      evidence implicating sympathetic neuron action in bone metabolism. The possible
      function of osteoclastogenesis, which could result in the initiation of
      sympathomimetic bone resorption, is also discussed.

PMID- 12203707
TI  - Calcitonin gene-related peptide (CGRP)-containing nerve fibers in bone tissue and
      their involvement in bone remodeling.
AB  - Bone remodeling is a process of bone renewal accomplished by osteoclastic bone
      resorption and osteoblastic bone formation. These two activities are regulated by
      systemic hormones and by local cytokines and growth factors. Moreover, the
      nervous system and certain neuropeptides seem to be involved in regulation of
      bone remodeling. In this paper, we focus on the distribution of CGRP-containing
      nerve fibers and their dynamics, and discuss the role of these fibers as a
      possible mechanism for nervous system involvement in regulation of bone
      remodeling. CGRP-immunoreactive nerve fibers are widely distributed in bone
      tissue, such as periosteum and bone marrow, and show apparent regional
      distribution with different densities. They are often associated with blood
      vessels and show a beaded appearance. The wide distribution of CGRP
      immunoreactive nerve fibers in bone tissue and the changes in distribution during
      bone development and regeneration suggest the involvement of these fibers in bone
      remodeling. The effect of CGRP on bone remodeling could partly be through its
      action on blood vessels, thereby regulating local blood flow. Moreover, in vitro
      biochemical data and the localization of CGRP-immunoreactive nerve fibers in the
      vicinity of bone cells suggest that they are directly involved in local
      regulation of bone remodeling by elevating the concentration of CGRP in the
      microenvironment around bone cells, especially during bone growth or repair.

PMID- 12203708
TI  - Tachykinins and tachykinin receptors in bone.
AB  - Tachykinins are neuropeptides that are widely distributed in the body and
      function as neurotransmitters and neuromodulators. Five tachykinin subtypes:
      substance P (SP), neurokinin A, neurokinin B, neuropeptide K, and neuropeptide
      gamma; and three receptor subtypes: neurokinin-1, -2, and -3 receptors, have been
      identified. SP was the first peptide of the tachykinin family to be identified.
      It is considered to be an important neuropeptide, and to function in the nervous
      system and intestine. However, recent advances in the analysis of SP receptors,
      particularly neurokinin-1 receptors (NK(1)-Rs) that have high affinity for SP,
      have demonstrated that NK(1)-Rs are distributed not only in neurons and immune
      cells, but also in other peripheral cells, including bone cells. This article
      reviews the current understanding of the distribution of SP and other tachykinins
      in bone, and the function of tachykinins, through neurokinin receptors. The
      distribution of tachykinin-immunoreactive axons and neurokinin receptors suggests
      that tachykinins may directly modulate bone metabolism through neurokinin
      receptors.

PMID- 12203709
TI  - Expression and regulatory role of receptors for vasoactive intestinal peptide in
      bone cells.
AB  - An intense network of nerve fibers can be demonstrated in skeletal tissues, not
      only in the periosteum but also within cortical bone, growth plate, and bone
      marrow. This neuro-osteogenic network expresses a restricted number of signalling
      molecules, including neuropeptides, neurotransmitters, and neurotrophins. Several
      lines of evidence indicate that receptors for these molecules are present on bone
      cells and that activation of these receptors leads to changes in bone cell
      activities. In addition, deletion of signalling molecules has been shown to alter
      bone metabolism. In the present review, these studies are summarized with a focus
      on distribution and effects of vasoactive intestinal peptide.

PMID- 12203710
TI  - Appraisal of SIMS applicability to boron studies in plants.
AB  - In the search for a new methodological approach applicable to the determination
      of the still poorly known primary role of boron in plant physiology, we have
      undertaken to appraise the potential of the SIMS method for the analytical
      imaging of the boron isotopes, (10)B and (11)B, at physiological concentrations
      in plants. With our own, CAMECA IMS4F SIMS ion analyser, and using O(2)(+) as
      primary ions for the detection of B(+) (plus (12)C(+) and (40)Ca(+)) secondary
      ions, we have been able to map quantitatively the two boron isotopes in control
      and boron-enriched plants, to evaluate boron concentrations at the level of
      individual cells and to determine boron isotopic ratios. This provides the
      opportunity to carry out the simultaneous labeling and imaging of boron, using
      enrichment with the stable isotopes, (10)B and (11)B. The method has also the
      potential for the simultaneous, quantitative detection of the boron isotopes and
      of the borate-binding sites in plant cells.

PMID- 12203711
TI  - Streptomycetes cultured on glass beads: Sample preparation for SEM.
AB  - We demonstrate the preparation of samples of streptomycetes (Streptomyces
      coelicolor, S. aureofaciens) cultured on glass beads (balotina) for scanning
      electron microscopy. The main trick of the method consists in immobilization of
      glass beads with low-melting agarose. The samples are then fixed in OsO(4) vapors
      followed by dehydration in vapors of absolute ethanol. No air-to-liquid
      transition during the sample preparation occurs. Consequently, whole cell cycle
      of streptomycetes in the term of mycelial morphology can readily be studied by
      this method.

PMID- 12203712
TI  - Method for preparing thin sections of untreated equine hoof horn for electron
      microscopic examination.
AB  - The preparation of hard tissues such as the equine hoof horn for electron
      microscopic examination is very difficult. In particular the penetration of
      fixatives and chemicals used during fixation and embedding is a problem. The
      objective of this study was to find and implement an alternative method enabling
      the preparation of high-quality thin sections of hoof horn and other hard tissue,
      which maintains the hard tissue ultrastructure and can be used for immuno
      labeling. Compared to commonly used fixation and embedding techniques, the
      preparation of thin sections from untreated material method saves time and
      material and provides equivalent ultrastructural information. Furthermore, thin
      sections from untreated material are significantly larger and more homogeneous,
      more resistant to the electron ray, as well as more suitable for sectioning. The
      electron microscopical pictures obtained allow a comparison to previous test
      results achieved with fixed and embedded material. Using the preparation of thin
      sections from untreated material method, fixation and embedding artifacts are
      avoided, providing a clearer interpretation of the electron microscopical
      findings. Considerable advantages are achieved by using immunohistochemical
      techniques with untreated horn specimens because fixation invariably decreases
      antigenicity.

PMID- 12203713
TI  - Increasing membrane contrast by means of imidazole-osmium post-fixation as
      exemplified by skeletal muscle fiber.
AB  - Until now, the interpretation of findings derived from investigations on membrane
      structures (T tubules, sarcoplasmic reticulum, the Golgi apparatus) in thick
      sections of mammalian muscle tissue has been limited in TEM due to the lack of
      sharp resolution of the membrane contours. This article shows how the imidazol
      osmium post-fixation of tissue blocks can be used to achieve well-contrasted,
      sharply defined membrane contours. Therefore, unstained sections from imidazol
      osmium post-fixed tissue can be examined immediately. But protein structures
      (e.g., ribosomes) remain uncontrasted with this technique. If needed, it is
      possible to visualize the protein structures by conventional section staining
      with uranyl acetate and lead citrate. This method is suitable for both ultrathin
      and thick sections (>150 nm).

PMID- 12203714
TI  - Phosphorescent metalloporphyrins as labels in time-resolved luminescence
      microscopy: effect of mounting on emission intensity.
AB  - In this study, we present an investigation of the effects of mounting media on
      the phosphorescence of metalloporphyrin stained microscopy samples. The samples
      were: (1) Platinum(II) coproporphyrin (=PtCP) stained porous Sephadex beads; (2)
      compact polystyrene microspheres coated with IgG-PtCP conjugate; and (3)
      immunocytochemically labeled human peripheral blood neutrophils. The human
      neutrophils in a mixed leukocyte population were fixed, permeabilized, and then
      immunolabeled with PtCP conjugate of monoclonal mouse IgG directed to the
      intracellular antigen myeloperoxidase. The samples were mounted in twelve
      different mounting media and studied with quantitative time-resolved luminescence
      imaging microscopy with respect to the intensity and stability of the
      phosphorescence signal. The results indicate that microscopy samples stained with
      PtCP exhibit the brightest phosphorescence emission in non-mounted form or when
      mounted in non-aqueous permanent mounting media.

PMID- 12203715
TI  - Localization of the novel Xin protein to the adherens junction complex in cardiac
      and skeletal muscle during development.
AB  - Previously, we demonstrated that chick embryos treated with antisense
      oligonucleotides against a striated muscle-specific Xin exhibit abnormal cardiac
      morphogenesis (Wang et al. [1999] Development 126:1281-1294); therefore, we
      surmised a role for Xin in cardiac development. Herein, we examine the
      developmental expression of Xin through immunofluorescent staining of whole-mount
      mouse embryos and frozen heart sections. Xin expression is first observed within
      the heart tube of embryonic day 8.0 (E8.0) mice, exhibiting a peripheral
      localization within the cardiomyocytes. Colocalization of Xin with both beta
      catenin and N-cadherin is observed throughout embryogenesis and into adulthood.
      Additionally, Xin is found associated with beta-catenin within the N-cadherin
      complex in embryonic chick hearts by coimmunoprecipitation. Xin is detected
      earlier than vinculin in the developing heart and colocalizes with vinculin at
      the intercalated disc but not at the sarcolemma within embryonic and postnatal
      hearts. At E10.0, Xin is also detected in the developing somites and later in the
      myotendon junction of skeletal muscle but not within the costameric regions of
      muscle. In cultured C2C12 myotubes, the Xin protein is found in many speckled and
      filamentous structures, coincident with tropomyosin in the stress fibers.
      Additionally, Xin is enriched in the regions of cell-cell contacts. These data
      demonstrate that Xin is one of the components at the adherens junction of cardiac
      muscle, and its counterpart in skeletal muscle, the myotendon junction.
      Furthermore, temporal and spatial expressions of Xin in relation to intercalated
      disc proteins and thin filament proteins suggest roles for Xin in the formation
      of cell-cell contacts and possibly in myofibrillogenesis.

PMID- 12203716
TI  - Expression of cathepsins B, H, K, L, and S during human fetal lung development.
AB  - Cathepsins are involved in lysosomal protein degradation, proenzyme activation,
      antigen processing, and hormone maturation. They are secreted by tumor cells and
      macrophages and catalyze the remodeling of extracellular matrix proteins. To gain
      insight into the expression pattern of cathepsins during fetal lung development,
      the expression of cathepsins B, H, K, L, and S at protein and mRNA levels were
      evaluated by using immunohistochemistry and in situ hybridization. Early
      expression of cathepsins B, H, and K was found in epithelial cells of the
      branching presumptive bronchi (<12th week of gestation). The most intense
      cathepsin K-specific immunoreactivity was found in developing airways with a
      lumen. Cathepsin K was found in epithelial cells only, whereas in contrast,
      cathepsins B and H were detected both in epithelial and interstitial cells.
      During fetal maturation, interstitial cells displayed cathepsin L
      immunoreactivity and, in the saccular phase (>26th week of gestation), both
      cathepsin L and S immunoreactivities. A continuous decline in the proportion of
      cathepsin H-positive interstitial CD68-positive cells was observed. These
      discrete temporal and spatial variations in cathepsin expression during
      organogenesis of the human lung indicate different physiological roles for the
      individual enzymes in different cell types and developmental stages.

PMID- 12203717
TI  - Expression and role of Roundabout-1 in embryonic Xenopus forebrain.
AB  - The receptor Roundabout-1 (Robo1) and its ligand Slit are known to influence axon
      guidance and central nervous system (CNS) patterning in both vertebrate and
      nonvertebrate systems. Although Robo-Slit interactions mediate axon guidance in
      the Drosophila CNS, their role in establishing the early axon scaffold in the
      embryonic vertebrate brain remains unclear. We report here the identification and
      expression of a Xenopus Robo1 orthologue that is highly homologous to mammalian
      Robo1. By using overexpression studies and immunohistochemical and in situ
      hybridization techniques, we have investigated the role of Robo1 in the
      development of a subset of neurons and axon tracts in the Xenopus forebrain.
      Robo1 is expressed in forebrain nuclei and in neuroepithelial cells underlying
      the main axon tracts. Misexpression of Robo1 led to aberrant development of axon
      tracts as well as the ectopic differentiation of forebrain neurons. These results
      implicate Robo1 in both neuronal differentiation and axon guidance in embryonic
      vertebrate forebrain.

PMID- 12203718
TI  - Fibroblast growth factor signaling regulates Dach1 expression during skeletal
      development.
AB  - Dach1 is a mouse homologue of the Drosophila dachshund gene, which is a key
      regulator of cell fate determination during eye, leg, and brain development in
      the fly. We have investigated the expression and growth factor regulation of
      Dach1 during pre- and postnatal skeletal development in the mouse limb to
      understand better the function of Dach1. Dach1 was expressed in the distal
      mesenchyme of the early embryonic mouse limb bud and subsequently became
      restricted to the tips of digital cartilages. Dach1 protein was localized to
      postmitotic, prehypertrophic, and early hypertrophic chondrocytes during the
      initiation of ossification centers, but Dach1 was not expressed in growth plates
      that exhibited extensive ossification. Dach1 colocalized with Runx2/Cbfa1 in
      chondrocytes but not in the forming bone collar or primary spongiosa. Dach1 also
      colocalized with cyclin-dependent kinase inhibitors p27 (Kip1) and p57 (Kip2) in
      chondrocytes of the growth plate and in the epiphysis before the formation of the
      secondary ossification center. Because fibroblast growth factors (FGF), bone
      morphogenetic proteins (BMP), and hedgehog molecules (Hh) regulate skeletal
      patterning of the limb bud and chondrocyte maturation in developing endochondral
      bones, we investigated the regulation of Dach1 by these growth and
      differentiation factors. Expression of Dach1 in 11 days postcoitus mouse limb
      buds in organ culture was up-regulated by implanting beads soaked in FGF1, 2, 8,
      or 9 but not FGF10. BMP4-soaked beads down-regulated Dach1 expression, whereas
      Shh and bovine serum albumin had no effect. Furthermore, FGF4 or 8 could
      substitute for the apical ectodermal ridge in maintaining Dach1 expression in the
      limb buds. Immunolocalization of FGFR2 and FGFR3 revealed overlap with Dach1
      expression during skeletal patterning and chondrocyte maturation. We conclude
      that Dach1 is a target gene of FGF signaling during limb skeletal development,
      and Dach1 may function as an intermediary in the FGF signaling pathway regulating
      cell proliferation or differentiation.

PMID- 12203719
TI  - Ascidian otx gene Hroth activates transcription of the brain-specific gene HrTRP.
AB  - The brain (sensory vesicle) of the ascidian larvae is thought to be homologous to
      the vertebrate forebrain and midbrain and, thus, is proposed as a simplified
      model to investigate mechanisms of brain formation in vertebrates. However, the
      genetic circuitry that governs formation of the sensory vesicle is largely
      unknown. To address this issue, we investigated the transcriptional regulation of
      the sensory vesicle-specific gene HrTRP by Hroth, the otx gene of the ascidian
      Halocynthia roretzi. A 133-bp 5'-flanking region of HrTRP, identified as a
      promoter that can drive expression of the reporter gene in the sensory vesicle,
      contains two otx binding consensus sites. When the two otx sites were deleted or
      mutated, the promoter activity of this region was decreased. Hroth overexpression
      can transactivate this promoter in an otx site-dependent manner. Transactivation
      of HrTRP promoter by Hroth overexpression was mimicked by overexpression of
      Hroth/VP16, which encodes a fusion protein of Hroth and the activator domain of
      VP16, and is suppressed by coexpression with Hroth/En, which encodes a fusion
      protein of Hroth and the Engrailed repressor domain. Finally, translational
      interference of Hroth by a morpholino oligonucleotide resulted in the reduction
      of HrTRP expression in the ascidian embryos. These results suggest that Hroth
      acts as a direct activator of HrTRP transcription during sensory vesicle
      development.

PMID- 12203720
TI  - Deficits in the posterior pharyngeal endoderm in the absence of retinoids.
AB  - Recent studies have shown that the pharyngeal endoderm plays a critically
      important role in directing the development of the pharyngeal region of the
      vertebrate embryo. We have, however, had few insights into how the pharyngeal
      endoderm itself is patterned. Recently, several studies have suggested that
      retinoic acid is required for the development of the pharyngeal endoderm. To
      study this proposal in greater depth, we have examined the development of the
      pharyngeal endoderm in the absence of retinoid signalling, by using the vitamin A
      deficient (VAD) quail model system. We find in early stages that, in the absence
      of retinoids, this territory extends further caudally than normal. Furthermore,
      as development proceeds, we find that the first pouch invariably forms, that the
      second pouch is abnormal, and that the third and fourth pharyngeal pouches never
      form. We do find, however, that dorsoventral patterning of the pharyngeal
      endoderm is unaffected. Finally, we have examined the expression patterns of
      RALDH2 before and during early development of the pharyngeal pouches. We find
      that this enzyme is expressed adjacent to the pharyngeal endoderm in tissues
      around the regressing anterior intestinal portal and that from stage 12 onward
      its anterior limit of expression lies at the level of the second pouch. This
      finding helps explain why the first pouch always forms in the absence of
      retinoids, and why defects are seen starting with the second and most evidently
      in the caudal pouches.

PMID- 12203721
TI  - Association of ASIP/mPAR-3 with adherens junctions of mouse neuroepithelial
      cells.
AB  - Polarity proteins play fundamental roles in asymmetric cell division, which is
      essential for the production of different types of cells in multicellular
      organisms. Here, we explore the localization of atypical PKC isotype-specific
      interacting protein (ASIP), a mammalian homologue of the Caenorhabditis elegans
      polarity protein PAR-3, in embryonic neural tissues. Although ASIP is localized
      on tight junctions in cultured epithelial cells, it localizes on adherens
      junctions outlined by beta-catenin and afadin at the luminal surface, an apical
      end of the neuroepithelium in developing mouse central nervous systems. Mammalian
      homologues of other C. elegans polarity proteins, mPAR-6 and aPKC, also localize
      in the adherens junctions. In dorsal root ganglia of the peripheral nervous
      system, ASIP is found predominantly in the cytoplasm of ganglion cells. In
      dividing preneural cells at the ventricular (luminal) surface of the embryonic
      telencephalon, ASIP localize in adherence junctions of luminal surface regardless
      of the axis of cell division. Therefore, only the daughter cell facing the lumen
      (apical daughter) may inherit ASIP when the division plate is oriented parallel
      to the surface. Given the roles of Bazooka, a Drosophila homologue of ASIP/PAR-3,
      in the asymmetric division of the Drosophila neuroblast, these observations
      suggest that ASIP, along with other polarity proteins and adherens junction
      proteins, plays an important role in neural cell differentiation by means of
      asymmetric cell division.

PMID- 12203722
TI  - Spatiotemporal distribution of heparan sulfate epitopes during myogenesis and
      synaptogenesis: a study in developing mouse intercostal muscle.
AB  - Formation of a basal lamina (BL) ensheathing developing skeletal muscle cells is
      one of the earliest events in mammalian skeletal muscle myogenesis. BL-resident
      heparan sulfate proteoglycans have been implicated in various processes during
      myogenesis, including synaptic differentiation. However, attention has focused on
      the proteoglycan protein core, ignoring the glycosaminoglycan moiety mainly
      because of a lack of appropriate tools. Recently, we selected a panel of anti
      heparan sulfate antibodies applied here to study the spatiotemporal distribution
      of specific heparan sulfate (HS) epitopes during myogenesis. In mouse intercostal
      muscle at embryonic day (E14), formation of acetylcholine receptor clusters at
      synaptic sites coincides with HS deposition. Although some HS epitopes show a
      general appearance throughout the BL, one epitope preferably clusters at synaptic
      sites but does so only from E16 onward. During elongation and maturation of
      primary myotubes, a process preceding secondary myotube development, significant
      changes in the HS epitope constitution of both synaptic and extrasynaptic BL were
      observed. As a whole, the data presented here strengthen previous observations on
      developmental regulation by BL components, and add to the putative roles of
      specific HS epitopes in myogenesis and synaptogenesis.

PMID- 12203723
TI  - Integration and differentiation of human embryonic stem cells transplanted to the
      chick embryo.
AB  - Human embryonic stem (ES) cells are pluripotent cells that can differentiate into
      a large array of cell types and, thus, hold promise for advancing our
      understanding of human embryology and for contributing to transplantation
      medicine. In this study, differentiation of human ES cells was examined in vivo
      by in ovo transplantation to organogenesis-stage embryos. Colonies of human ES
      cells were grafted into or in place of epithelial-stage somites of chick embryos
      of 1.5 to 2 days of development. The grafted human ES cells survived in the chick
      host and were identified by vital staining with carboxyfluorescein diacetate or
      use of a green fluorescent protein-expressing cells. Histologic analysis showed
      that human ES cells are easily distinguished from host cells by their larger,
      more intensely staining nuclei. Some grafted cells differentiated en masse into
      epithelia, whereas others migrated and mingled with host tissues, including the
      dorsal root ganglion. Colonies grafted directly adjacent to the host neural tube
      produced primarily structures with the morphology and molecular characteristics
      of neural rosettes. These structures contain differentiated neurons as shown by
      beta-3-tubulin and neurofilament expression in axons and cell bodies. Axons
      derived from the grafted cells penetrate the host nervous system, and host axons
      enter the structures derived from the graft. Our results show that human ES cells
      transplanted in ovo survive, divide, differentiate, and integrate with host
      tissues and that the host embryonic environment may modulate their
      differentiation. The chick embryo, therefore, may serve as an accessible and
      unique experimental system for the study of in vivo development of human ES
      cells.

PMID- 12203724
TI  - Morphologic transformation of the thymus in developing zebrafish.
AB  - The morphologic transformation of the developing zebrafish thymus from 1 week
      postfertilization (wpf) to 15 wpf is described. The thymus overall morphology
      changed from a small pouch-like shape at 1 wpf to a conical shape between 2 and 3
      wpf before acquiring a more complex shape from 4 wpf onward. Rapid growth rate
      along the lateral axis at the region near the pharyngeal epithelium occurred
      between 1 and 2 wpf, whereas rapid growth rate along the dorsal-ventral axis
      occurred between 3 and 6 wpf. Expansion of thymocyte population beginning from 1
      wpf became more evident by 2 to 3 wpf, as indicated by the apparent increase of
      different sizes of lymphocytes, recombination activating gene-1 (rag-1), and T
      cell antigen receptor alpha chain constant region (TCRAC) -positive cells. Tissue
      section in situ hybridization (ISH) analysis with rag-1 probe reveals that cortex
      medullary regionalization has begun between 1 and 2 wpf as rag-1 expression
      clearly demarcated the cortex, whereas the medulla was rag-1 negative. The
      presence of TCRAC-positive cells in the medulla by 2-3 wpf, suggests that the
      thymic selection processes had begun. The zebrafish thymus is morphologically
      mature by 3 wpf. Early signs of thymic involution were observed in zebrafish aged
      15 wpf.

PMID- 12203725
TI  - Extensive vascularization of developing mouse ovaries revealed by caveolin-1
      expression.
AB  - Expression screening for genes preferentially expressed in mouse fetal ovaries
      relative to testes identified Cav-1 as a candidate female-specific gene. Cav-1
      encodes caveolin-1, a component of the cell membrane invaginations known as
      caveolae, which are involved in lipid regulation and signal transduction. In situ
      hybridization revealed high levels of Cav-1 mRNA in developing ovaries, compared
      with moderate or low levels in testes. Analysis of caveolin-1 protein
      distribution by immunofluorescence showed this difference to be due to the
      development of a dense and complex vascular network in the developing ovary.
      These observations point to a higher degree of differentiation and organization
      of the early stage mammalian ovary than previously suspected.

PMID- 12203726
TI  - Mouse strain-specific patterns of mammary epithelial ductal side branching are
      elicited by stromal factors.
AB  - Variations in mammary ductal side branching patterns are known to occur between
      different strains of mice and this is related to the rate of spontaneous mammary
      cancers, which are increased in those strains which show highly side-branched
      mammary architecture. The cause of the variation in ductal side branching between
      mouse strains is unknown, but epithelial, stromal, and endocrine factors have
      been implicated. To define the mammary elements responsible for controlling
      strain-specific ductal side branching patterns, we formed recombined mammary
      glands from epithelial and stroma elements taken from highly side-branched 129
      and poorly side-branched C57BL/6J mammary glands and transplanted them to Rag1(-/
      ) hosts on the inbred C57BL/6J background. When 129 epithelium was recombined
      with C57BL/6J stroma the poorly side-branched C57BL/6J pattern was observed.
      C57BL/6J epithelium recombined with 129 stroma resulted in development of the
      highly side- branched pattern, as did 129 epithelium recombined with 129 stroma.
      All transplants used the same C57BL/6J endocrine background, demonstrating that
      strain differences in the mammary stroma are responsible for the strain-specific
      ductal side branching patterns and that strain differences in epithelium or
      endocrine background play no part. Genes currently known to influence side
      branching by means of the stroma include activin/inhibin, epidermal growth factor
      receptor (EGFR), Wnt-2, Wnt-5a, and Wnt-6. Of these, Wnt-5a mRNA expression was
      decreased in 129 mammary glands compared with C57BL/6J mammary glands, but in F2
      129:C57BL/6J animals Wnt-5a mRNA expression level did not correlate with the
      highly variable side branching patterns observed. These experiments exclude
      variation in the expression level of known candidate genes as the mechanism
      responsible. Regardless of underlying mechanism, transplantation without regard
      to the genetic background of the stromal donor, whether inbred or mixed, will
      compromise experiments with side branching and associated gene expression
      endpoints.

PMID- 12203727
TI  - atonal is required for exoskeletal joint formation in the Drosophila auditory
      system.
AB  - Hearing relies on the delicate arrangement of mechanoreceptor neurones and an
      acoustomechanical interface. The concerted action of these neural and non-neural
      components is essential to audition, raising the question of whether they also
      develop in a concerted way. Drosophila hears with its antennae. A specialized
      antennal joint allows the distal part of the antenna to vibrate in response to
      sound and, thus, to serve as the sound receiver. This receiver's vibration is
      transduced by a chordotonal sense organ (CHO) that is closely associated with the
      joint. Here, we report that atonal (ato), the proneural gene for CHOs, is
      required for the formation of this antennal joint. Biophysical measurements in
      hemi- and homozygous ato(1) mutant flies show that, in addition to eliminating
      the auditory CHO, loss of ato function makes the antennal receiver insensitive to
      sound, impairing its auditory function. Anatomically, the cause for this
      mechanical effect resides in the deprivation of mobile exoskeletal joint
      structures. Hence, ato, the homologue of mouse Math1, is required for the
      formation of both the auditory CHO and joint, providing a genetic link between
      the very neural and exoskeletal components that together transform fly antennae
      into ears.

PMID- 12203729
TI  - Craniofacial abnormalities resulting from targeted disruption of the murine Sim2
      gene.
AB  - Sim2 is a member of the basic helix-loop-helix PAS transcription factor gene
      family and is evolutionarily related to the Drosophila single-minded gene, a key
      regulator of central nervous system midline development. In an effort to
      determine the biological roles of Sim2 in mammalian development, we disrupted the
      murine Sim2 gene through gene targeting. Mice homozygous for the disrupted allele
      (Sim2 -/-) exhibit a cleft of the secondary palate and malformations of the
      tongue and pterygoid processes of the sphenoid bone. These craniofacial
      malformations are the most probable cause of aerophagia (air swallowing with
      subsequent accumulation of air in the gastrointestinal tract) and postnatal death
      exhibited by Sim2 -/- mice. The developing palates of the Sim2 -/- mice are
      hypocellular, and at embryonic day 14.5 contain excess extracellular matrix
      component hyaluronan (HA) compared with heterozygotes and homozygous wild-type
      littermates. HA plays an important role in the regulation and mechanics of palate
      development. Its premature accumulation in Sim2 -/- animal palates suggests a
      regulatory role for Sim2 in HA synthesis and in the establishment of craniofacial
      architecture.

PMID- 12203728
TI  - Transition between proliferation and differentiation for lens epithelial cells is
      regulated by Src family kinases.
AB  - As in many cell types, lens cells must withdraw from the cell cycle before they
      initiate their differentiation. The involvement of Src family kinases (SFKs) in
      this key initiating event in cell differentiation was examined in lens epithelial
      cell cultures. SFK activity was suppressed with the specific inhibitor PP1. This
      induced expression of the cyclin-dependent kinase (CDK) inhibitors p27 and p57
      and suppressed lens epithelial cell proliferation. Therefore, inhibition of SFK
      activity created conditions permissive for undifferentiated lens epithelial cells
      to withdraw from the cell cycle. Growth of the lens epithelial cell cultures in
      the presence of PP1 induced expression of filensin and CP49, lens differentiation
      specific intermediate filament proteins, providing evidence that suppression of
      SFK activity also promoted the initiation of lens cell differentiation. The
      mechanism by which PP1 signaled cell cycle withdrawal and commitment to
      differentiation was shown to involve induction of N-cadherin cell-cell junction
      assembly and reorganization of the actin cytoskeleton from stress fibers to
      cortical filaments. This result was supported by the compaction of the epithelial
      monolayer in response to PP1, a morphogenetic change that we have previously
      shown to be dependent on N-cadherin function and a hallmark of the commencement
      of the lens differentiation program in culture. The results presented in this
      study suggest that the decision of lens epithelial cells to withdraw from the
      cell cycle and initiate differentiation requires inhibition of SFKs and the
      formation of N-cadherin cell-cell junctions.

PMID- 12203730
TI  - Autonomous regulation of muscle fibre fate during metamorphosis in Xenopus
      tropicalis.
AB  - A key event in metamorphosis of anuran amphibians is tail resorption. This
      composite structure includes epidermal cells, spinal cord, muscle fibres and
      connective tissue. It is unclear how resorption proceeds and to what extent the
      signals for the death process are transmitted between cells. We determined the
      kinetics of metamorphosis, apoptosis, and tail regression in the diploid anuran,
      Xenopus tropicalis, a species more suited to genetic analysis than the
      pseudotetraploid, Xenopus laevis. Metamorphosis was found to proceed at a regular
      and predictable rate in X. tropicalis but not in X. laevis. Caspase 3 activity
      and mRNA levels were correlated with TdT-mediated dUTP nick end-labeling (TUNEL)
      signalling and most markedly increased in tail muscle and spinal cord. It has
      been proposed that muscles die as a result of loss of connectivity with the
      surrounding matrix. To test this hypothesis, we used direct DNA injection in
      trunk and tail muscle to overexpress Xenopus Bcl-X(L) (xR11), an anti-apoptotic
      gene, along with a marker gene (luciferase or GFP). xR11 significantly inhibited
      the cell death process in both trunk and tail muscle. This protection was
      functional even up to stage 64 on completion of tail regression. We conclude that
      (1) somatic gene transfer can be applied to analyse cell fate in X. tropicalis,
      and (2) that muscle death can be abrogated despite extracellular matrix loss.

PMID- 12203731
TI  - Optimality in the developing vascular system: branching remodeling by means of
      intussusception as an efficient adaptation mechanism.
AB  - The theory of bifurcating vascular systems predicts vessel diameters that are
      related to optimality criteria like minimization of pumping energy or of building
      material. However, mechanisms for producing the postulated optimality have not
      been described so far, and quantitative data on bifurcation diameters during
      development are scarce. We used an embryonic vascular bed that rapidly grows and
      adapts to changing hemodynamic conditions, the chicken chorioallantoic membrane
      (CAM), and correlated vascular cast and tissue section morphology with in vivo
      time-lapse video monitoring. The bifurcation exponent delta and associated
      parameters were quantitatively assessed in arterial and venous microvessels
      ranging in diameter from 30 to 100 microm. We observed emergence of optimality by
      means of intussusception, i.e., formation of transvascular tissue pillars. In
      addition to intussusceptive microvascular growth (IMG = expansion of capillary
      networks) and intussusceptive arborization (IAR = formation of feeding vessels
      from capillaries) the observed intussusception at bifurcations represents a third
      variant of nonsprouting angiogenesis. We call it intussusceptive branching
      remodeling (IBR). IBR occurred in vessels of considerable diameter by means of
      two alternative mechanisms: either through pillars arising close to a
      bifurcation, which increased in girth until they merged with the connective
      tissue in the bifurcation angle; or through pillars arising at some distance from
      the bifurcation point, which then expanded by formation of ingrowing tissue folds
      until they became connected to the tissue of the bifurcation angle. Morphologic
      evidence suggests that IBR is a wide-spread phenomenon, taking place also in
      lung, intestinal, kidney, eye, etc., vasculature. Irrespective of the mode
      followed, IBR led to a branching pattern close to the predicted optimum, delta =
      3.0. Significant differences were observed between delta at arterial bifurcations
      (2.70 to 2.90) and delta at venous bifurcations (2.93 to 3.75). IBR, by means of
      eccentric pillar formation and fusion, was also involved in vascular pruning.
      Experimental changes in CAM hemodynamics (by locally increasing blood flow)
      induced onset of IBR within less than 1 hr. Our study provides morphologic and
      quantitative evidence that a similar cellular machinery is used for all three
      variants of vascular intussusception, IMG, IAR, and IBR. It thus provides a
      mechanism of efficiently generating complex blood transport systems from limited
      genetic information. Differential quantitative outcome of IBR in arteries and
      veins, and the experimental induction of IBR strongly suggest that hemodynamic
      factors can instruct embryonic vascular remodeling toward optimality.

PMID- 12203732
TI  - Perlecan participates in proliferation activation of quiescent Drosophila
      neuroblasts.
AB  - Drosophila neuroblasts act as stem cells. Their proliferation is controlled
      through cell cycle arrest and activation in a spatiotemporal pattern. Several
      genes have been identified that control the pattern of neuroblast quiescence and
      proliferation in the central nervous system (CNS), including anachronism (ana),
      even skipped (eve) and terribly reduced optic lobes (trol). eve acts in a non
      cell-autonomous manner to produce a transacting factor in the larval body that
      stimulates cell division in the population of quiescent optic lobe neuroblasts.
      ana encodes a secreted glial glycoprotein proposed to repress premature
      proliferation of optic lobe and thoracic neuroblasts. trol was shown to act
      downstream of ana to activate proliferation of quiescent neuroblasts either by
      inactivating or bypassing ana-dependent repression. Here, we show that trol codes
      for Drosophila Perlecan, a large multidomain heparan sulfate proteoglycan
      originally identified in extracellular matrix structures of mammals. The results
      suggest that trol acts in the extracellular matrix and binds, stores, and
      sequesters external signals and, thereby, participates in the stage- and region
      specific control of neuroblast proliferation.

PMID- 12203733
TI  - Cardiac looping in experimental conditions: effects of extraembryonic forces.
AB  - The chick embryo is a popular experimental model used to study the mechanisms of
      cardiac looping. To facilitate oxygen transport, researchers typically culture
      the embryo on the surface of the medium. Such preparations, however, expose the
      embryo and the heart to surface tension that is not present in ovo. This study
      investigates the influence that surface and extraembryonic membrane tensions have
      on looping morphology. To eliminate surface tension, we developed a technique in
      which the embryo is cultured under a thin layer of fluid. To eliminate membrane
      tension, the membrane was removed. Our results show that both tensions can affect
      looping, with surface tension potentially having a much greater effect. Moreover,
      we show that surface tension can alter results in one classic looping experiment.

PMID- 12203734
TI  - TnIfast IRE enhancer: multistep developmental regulation during skeletal muscle
      fiber type differentiation.
AB  - To identify developmental steps leading to adult skeletal muscle fiber-type
      specific gene expression, we carried out transgenic mouse studies of the IRE
      enhancer of the quail TnIfast gene. Histochemical analysis of IRE/herpesvirus tk
      promoter/beta-galactosidase reporter transgene expression in adult muscle
      directly demonstrated IRE-driven fast vs. slow fiber-type specificity, and
      IIB>IIX>IIA differential expression among the fast fiber types: patterns similar
      to those of native-promoter TnIfast constructs. These tissue- and cell-type
      specificities are autonomous to the IRE and do not depend on interactions with a
      muscle gene promoter. Developmental studies showed that the adult pattern of IRE
      driven transgene expression emerges in three steps: (1) activation during the
      formation of primary embryonic (presumptive slow) muscle fibers; (2) activation,
      to markedly higher levels, during formation of secondary (presumptive fast)
      fibers, and (3) differential augmentation of expression during early postnatal
      maturation of the IIB, IIX, IIA fast fiber types. These results provide insight
      into the roles of gene activation and gene repression mechanisms in fiber-type
      specificity and can account for apparently disparate results obtained in previous
      studies of TnI isoform expression in development. Each of the three IRE-driven
      developmental steps is spatiotemporally associated with a different major
      regulatory event at the fast myosin heavy chain gene cluster, suggesting that
      diverse muscle gene families respond to common, or tightly integrated, regulatory
      signals during multiple steps of muscle fiber differentiation.

PMID- 12203735
TI  - Clonal analysis of patterns of growth, stem cell activity, and cell movement
      during the development and maintenance of the murine corneal epithelium.
AB  - Patterns of growth and cell movement in the developing and adult corneal
      epithelium were investigated by analysing clonal patches of LacZ-expressing cells
      in chimeric and X-inactivation mosaic mice. It was found that cell proliferation
      throughout the basal corneal epithelium during embryogenesis and early postnatal
      life creates a disordered mosaic pattern of LacZ(+) clones that contrasts with
      patterns of proliferation and striping produced during the later embryonic stages
      of retinal pigmented epithelium development. The early mosaic pattern in the
      corneal epithelium is replaced in the first 12 postnatal weeks by an ordered
      pattern of radial stripes or sectors that reflects migration without mixing of
      the progeny of clones of limbal stem cells. In contrast to previous assumptions,
      it was found that maturation of the activity of limbal stem cells and the pattern
      of migration of their progeny are delayed for several weeks postnatally. No
      evidence was found for immigration of the progeny of stem cells until the 5th
      postnatal week. There are approximately 100 clones of limbal stem cells
      initially, and clones are lost during postnatal life. Our studies provide a new
      assay for limbal and corneal defects in mutant mice.

PMID- 12203736
TI  - Synthetic matrix metalloproteinase inhibitor decreases early cardiac neural crest
      migration in chicken embryos.
AB  - During early embryonic development, cardiac neural crest (NC) cells emerge from
      the forming neural tube, migrate beneath the ectoderm, enter the pharyngeal
      arches, and subsequently participate in the septation of the heart. Like tumor
      cells, NC cells penetrate through basement membranes and invade extracellular
      matrix during their emigration and migration and, therefore, are liable to use
      similar invasive mechanisms. Matrix metalloproteinases (MMPs) are a family of
      zinc proteolytic enzymes known to be important in cell migration and invasion of
      normal and metastatic cells. In an earlier study, we found that the spatial and
      temporal distribution pattern of MMP-2 positively correlates with cardiac NC
      migration, suggesting MMP enzymatic activity may be important in mediating
      cardiac cell NC migration. To test this hypothesis, a synthetic MMP inhibitor,
      KB8301, was used to block MMP enzymatic activity during in vitro and in vivo
      cardiac NC cell migration in chick embryos. Injection of KB8301 into the cell
      free space adjacent to the neural tube at the level of the second somite before
      the NC cells emigrated caused major morphologic anomalies in embryos and
      disrupted cardiac NC morphogenesis. Unilateral injection of KB8301 at lower
      concentrations, significantly decreased cardiac NC migration on the injected side
      compared with the noninjected side and compared with that of the injected
      controls. This decrease correlated with a decrease in MMP activity in the embryos
      and was not attributable to differences in embryo size or rate of embryonic
      development after injection. KB8301 also significantly decreased the rate of NC
      cell motility and distance NC cells migrated from explanted neural tubes and
      increased cell area and perimeter. These data suggest that MMP enzymatic activity
      is an important mediator of early cardiac NC migration and that perturbation of
      endogenous MMP activity may lead to NC-related congenital defects.

PMID- 12203738
TI  - A zebrafish unc-45-related gene expressed during muscle development.
AB  - We report the isolation and expression pattern of zebrafish unc45r, a gene
      related to Caenorhabditis elegans unc-45. UNC-45 is a muscle-specific protein
      thought to interact with myosin and promote the assembly of muscle thick
      filaments during C. elegans development. Zebrafish Unc45r shares sequence
      features with C. elegans UNC-45, including three tetratricopeptide repeats and a
      CRO1/She4p homology domain. unc45r is expressed in mesoderm adjacent to the
      dorsal midline during late gastrula stages and is coexpressed with muscle
      specific genes in somitic mesoderm during development of trunk skeletal muscle.
      unc45r is also expressed in cranial skeletal muscle as well as in cardiac and
      smooth muscle. The isolation of a muscle-specific unc-45 related gene from
      zebrafish suggests a common mechanism for muscle filament assembly between
      vertebrates and invertebrates.

PMID- 12203737
TI  - Distribution of the titf2/foxe1 gene product is consistent with an important role
      in the development of foregut endoderm, palate, and hair.
AB  - Titf2/foxe1 is a forkhead domain-containing gene expressed in the foregut, in the
      thyroid, and in the cranial ectoderm of the developing mouse. Titf2 null mice
      exhibit cleft palate and either a sublingual or completely absent thyroid gland.
      In humans, mutations of the gene encoding for thyroid transcription factor-2 (TTF
      2) result in the Bamforth syndrome, characterized by thyroid agenesis, cleft
      palate, spiky hair, and choanal atresia. Here, we report a detailed expression
      pattern of TTF-2 protein during mouse embryogenesis and show its presence in
      structures where it has not been described yet. At embryonic day (E) 10.5, TTF-2
      is expressed in Rathke's pouch, in thyroid, and in the epithelium of the
      pharyngeal wall and arches, whereas it is absent in the epithelium of the
      pharyngeal pouches. According to this expression, at E13.5, TTF-2 is present in
      endoderm derivatives, such as tongue, palate, epiglottis, pharynx, and
      oesophagus. Later in embryogenesis, we detect TTF-2 in the choanae and whiskers.
      This pattern of expression helps to define the complex phenotype displayed by
      human patients. Finally, we show that TTF-2 is a phosphorylated protein. These
      results help to characterize the domains of TTF-2 expression, from early
      embryogenesis throughout organogenesis, providing more detail on the potential
      role of TTF-2 in the development of endoderm and ectoderm derived structures.

PMID- 12203739
TI  - Developmental expression of alpha4 protein phosphatase regulatory subunit in
      tissues affected by Opitz syndrome.
AB  - Mutations in the Mid1 gene are responsible for X-linked Opitz syndrome,
      characterized by midline defects of the brain, face, heart, and trachea. The
      regulatory subunit alpha4 binds protein phosphatase 2A to Mid1 and promotes Mid1
      dephosphorylation, in opposition to MAP kinase. To examine the relationship
      between alpha4 expression and human defects in Opitz syndrome, developmental
      expression of alpha4 in embryonic day (E) 8-E16 mouse embryos was mapped by
      immunohistochemistry. At E10, alpha4 was first detected only in the heart. At
      E11, alpha4 was expressed in epithelium of the mandibular and maxillary arches
      and in specific subsets of mesenchymal cells within the arches. The fetal heart
      and brain also highly expressed alpha4. At E16, alpha4 expression broadened to
      include the heart, brain, skeletal muscle, and tracheal and esophageal epithelium
      but not smooth muscle. Consistent with immunolocalization in embryos, Western
      immunoblotting of adult rabbit tissues demonstrated high levels of alpha4
      expression in brain, heart, lung, liver, and skeletal muscle with low expression
      in kidney, uterus, and intestine. Expression in slow type I skeletal muscle was
      much higher than in fast type II muscle. By using double immunohistochemical
      staining, alpha4 was coexpressed in mouse skeletal muscle cells containing slow
      type myosin. Expression of alpha4 overlaps with the tissue defects in Opitz
      syndrome. The alpha4 gene lies in the linkage interval for FG syndrome,
      characterized by skeletal muscle and brain defects that coincide closely to the
      expression pattern of alpha4.

PMID- 12203740
TI  - Expression of the ankyrin repeat domain 6 gene (Ankrd6) during mouse brain
      development.
AB  - The structure and developmental expression pattern of the ankyrin repeat domain 6
      (Ankrd6) gene, initially named Diversin, were studied in the mouse. Ankrd6 is
      transcribed as a 5.8-kb mRNA composed of 15 exons that encodes a 712 amino acid
      protein with 6 ankyrin repeats. Ankrd6 is expressed prominently in the developing
      brain from E12 to maturity, suggesting a role during brain development. In
      embryos, expression is maximal in ventricular zones of neuronal proliferation and
      intermediate zones of neuronal migration and extends to postmigratory neuronal
      fields during the postnatal period. In the mature brain, the Ankrd6-related
      signal is highest in cortical layer II, granule cells of the dentate gyrus,
      olfactory granules and a subset of Purkinje cells in the vestibulocerebellum.
      Ankrd6 is related to the Drosophila gene Diego, which interacts with Flamingo in
      the regulation of planar cell polarity (Feiguin et al., 2001). However, the
      canvas of Ankrd6 expression does not match closely that of the three mouse
      Flamingo homologs, Celsr1-3 (Tissir et al., 2002). These data suggest that Ankrd6
      may be involved in brain development in interaction with Celsr/Flamingo but also
      other signaling pathways.

PMID- 12203741
TI  - A POMS short form for cancer patients: psychometric and structural evaluation.
AB  - The internal consistency, validity, and factor structure of the Shacham shortened
      version (37 items) of the 65-item profile of mood states (POMS) were examined
      with a sample of 428 cancer patients who were awaiting bone marrow
      transplantation. Cronbach's alphas ranging from 0.78 to 0.91 were obtained for
      each of the six subscales of the POMS-short form (POMS-SF) and for the total 37
      item scale. Correlations with the CES-D, the Self-Rated Karnofsky, the MOS SF-20
      Physical Functioning, and the Bradburn Positive and Negative Affect Scales
      provided evidence of the convergent and discriminant validity of the POMS-SF.
      Results of a confirmatory factor analysis were supportive of the 6-factor
      interpretation of the POMS items in the 37-item version of the POMS.

PMID- 12203742
TI  - Effects of a brief intervention on social support and psychiatric morbidity in
      breast cancer patients.
AB  - (1) To cross-sectionally and longitudinally investigate relationships between the
      availability and adequacy of both close personal attachment and interactional
      support, and psychiatric morbidity in a sample of early stage breast cancer
      patients participating in a 6-week psychoeducational intervention. (2) To address
      the question of directionality in these longitudinal relationships. (3) To
      investigate the effects of the intervention on levels of social support. Eighty
      nine women were enrolled in the study, and randomly assigned to either the
      treatment or control condition. They were evaluated with the Interview Schedule
      for Social Interaction (ISSI), the Beck Depression Inventory (BDI), the Global
      Severity Index (GSI) of the Symptom Checklist (SCL) -90-R, and the Structured
      Clinical Interview for DSM-III-R (SCID) at three time periods: baseline (pre
      intervention), 1 year post-intervention and 2 years post-intervention.
      Relationships between social support and the psychiatric measures were evaluated
      both cross-sectionally and longitudinally. Cross-sectionally, there were strong
      associations at each time period between being diagnosed with a DSM-III-R Axis I
      disorder and having less adequate perceived social support from both close
      relationships and more distant social ties. Initial levels of psychiatric
      symptoms on the BDI and GSI were better predictors of later social support than
      initial social support variables were of later psychiatric symptoms.
      Participation in the group intervention did not result in changes in social
      support at 1 or 2 years post-intervention. Cross-sectionally, there was a strong
      relationship between social support and psychiatric morbidity in these patients
      with early-stage breast cancer. Longitudinally, it appeared that although social
      support influenced psychiatric symptomatology somewhat, the influence of
      psychiatric symptoms on social support was greater. This illustrates the
      importance of both working to bolster social support and dealing with psychiatric
      symptomatology in this population.

PMID- 12203743
TI  - Lay constructions of decision-making in cancer.
AB  - In recent years there has been increased emphasis on involving people in decision
      making about their medical care. However, few studies have addressed the
      questions of why women with cancer want information, and what they believe to be
      the important factors influencing their decision-making. In order to examine
      these questions 20 women with cancer were interviewed via telephone 2 weeks after
      their first consultation with one of 6 medical oncologists. Recruitment continued
      until informational redundancy was achieved. While women cited the risk of
      recurrence, life expectancy, side-effects, and quality of life as influencing
      their decisions, they placed at least as much emphasis on their personal
      relationship with the specialist. These 'personal' factors included: feeling that
      the doctor cared for, understood and respected them; that they could trust and
      have confidence in the doctor; that the doctor would give them enough time; that
      they would be listened to; and that the doctor would be open and honest. If these
      factors were felt to be present, many women were happy to accept the doctor's
      recommendation, confident that they would receive the optimum treatment. However,
      many women felt there was no decision to be made: further treatment must be
      undertaken to reduce risk, and minor variations in the treatment protocol were of
      little significance. These results underline the importance of establishing
      patient priorities and concerns before embarking on discussions about treatment.

PMID- 12203744
TI  - Prostate cancer and health-related quality of life: a review of the literature.
AB  - With the established effectiveness of diverse treatments for prostate cancer,
      identification of the physical and psychosocial consequences of the disease and
      various treatments becomes critical. We review the literature on the effects of
      prostate cancer and its treatment on health-related quality of life (HRQoL).
      Studies show that prostate cancer and its treatment affect both disease-specific
      HRQoL (i.e. urinary, sexual, and bowel function) as well as general HRQoL (i.e.
      energy/vitality, performance in physical and social roles). Yet, these effects
      appear to differ across stage of disease and type of treatment. We outline
      evidence from three sources: (1) studies that compare men with the disease with
      an age-matched sample of men without the disease, (2) studies that assess men
      with the disease across time, and (3) cross-sectional studies that highlight
      predictors of HRQoL. Future research directions are discussed.

PMID- 12203745
TI  - 'The doctor knows best' revisited: physician perspectives.
AB  - An ethnographic study was undertaken to observe in vivo medical encounters
      between oncology physicians and breast cancer patients. The aim of the study was
      to gain an inside view of how physicians and patients conceptualize the decision
      making process during cancer diagnosis and treatment. The confluence of the
      changes in the role of women in society, the shifting requirements for the
      delivery of medical services and a complex array of medical options have all
      contributed to changes in the role of the physician from 'the doctor knows best'
      to a more reciprocal role. The study revealed physician-patients perspectives
      that may facilitate future medical encounters. In addition, some troubling
      practices were observed that raise dilemmas about the parameters of informed
      consent and ethical concerns regarding how medical options are presented.

PMID- 12203746
TI  - Information exchange in oncology outpatient clinics: source, valence and
      uncertainty.
AB  - A large literature of doctor-patient communication exists, yet little is known
      about how symptom information is communicated in cancer care. This qualitative
      study explores the exchange of symptom and clinical information between cancer
      patients and oncologists in outpatient clinics of a regional teaching hospital.
      Verbatim transcripts of consultations between 14 doctors and 43 post-treatment
      follow-up patients from eight consultants' clinics were subjected to analytic
      induction and microinteractional analysis techniques. Findings from these
      analyses indicate that information about patients was accorded varying relevance
      by doctors depending upon its source, valence and certainty. Doctors' requests
      for information was contingent upon certainty of clinical information. Symptom
      information was elicited from patients only when clinical information with high
      certainty was unavailable. If negative patient information was volunteered, it
      was not addressed when positive clinical information was present and cancer
      treatment was not indicated. It appears that information in outpatient oncology
      consultations is organised according to a hierarchy and is used to make treatment
      decisions and not primarily for symptom management.

PMID- 12203747
TI  - Patient initiated follow up of breast cancer.
AB  - This paper reports on a randomised controlled trial assessing two types of
      outpatient follow up for women previously treated for stage 1 breast cancer now
      in remission. These were standard clinic follow up (n = 31, age range: 48-83
      years) and patient initiated follow up (n = 30, age range 53-87 years). The
      latter method involved giving the women written information on the signs and
      symptoms of recurrence and instructing them to telephone the Breast Care Nurse if
      they encountered any problems. The groups were compared in terms of cancer and
      breast cancer-specific quality of life, and psychological morbidity at
      recruitment, 6 months and 1 year. Satisfaction with follow up was assessed at 6
      months and 1 year. Details regarding contact with healthcare professionals were
      collected at 1 year. There were no major differences in quality of life and
      psychological morbidity between the groups although more women in the standard
      clinic group reported reassurance and being checked as advantages whereas more
      women in the patient initiated follow up group reported convenience as an
      advantage. Patient initiated follow up is a potential alternative to standard
      clinic follow up for this group of women and appears to have no adverse effects.
      This could enable a cost saving to be made.

PMID- 12203748
TI  - Affected self-respect and self-value: the impact of breast cancer treatment on
      self-esteem and QoL.
AB  - There is a need to understand and explain the impact of breast cancer on women's
      self-esteem and quality of life. The purpose of the present study was to identify
      and describe, from the perspective of the women's lived experiences, the impact
      of breast cancer on women's self-esteem and elucidate its impact on their quality
      of life. Thirteen women diagnosed as having breast cancer were interviewed about
      these phenomena. The narrated interviews, tape-recorded and transcribed verbatim
      were analysed and interpreted using a qualitative text analysis, based on the
      following question: What sense of satisfaction and importance is there with
      respect to the women's value and preferences? The findings were interpreted as
      affected self-respect and self-value, which were found to be important aspects
      affecting the quality of life of these women, within this lies the satisfaction
      of desire, to be respected and loved as the women they are. Concerns related to
      their quality of life seemed to be heightened when treatment has been completed,
      i.e. when the psychological effects of the treatment experience become a reality.
      Health professional need to be aware of how to recognise these women, in order to
      provide them with support to maintain a positive self-esteem to enhance quality
      of life as a caring outcome.

PMID- 12203751
TI  - Disentangling the effects of morbidity and life expectancy on labor market
      outcomes.
AB  - Using a unique longitudinal dataset tracking the experiences of patients
      diagnosed with HIV+ disease, this paper develops and estimates a model capable of
      recovering the effect of revisions in life expectancy on labor market outcomes.
      The data allow us to estimate the effect of changes in health status (as
      objectively measured by CD4 counts) and the impact of learning that one is HIV+,
      which we interpret as a negative shock to life expectancy. Both parametric and
      distribution-free models robustly indicate that decreases in health have little
      effect on labor demand but decrease probability of employment. We conclude that,
      in this sample, negative association between income and health is attributable
      mostly to the effect of altered incentives induced by changes in life expectancy.

PMID- 12203752
TI  - Rational addiction to alcohol: panel data analysis of liquor consumption.
AB  - Utilizing a panel data set of 42 states over the period 1959-1994, this paper
      estimates a rational addiction model for liquor consumption for the US. The
      empirical evidence is consistent with the rational addiction hypothesis proposed
      by Becker and Murphy. However, the results are sensitive to the assumption of
      homogeneity across states or over time.

PMID- 12203753
TI  - Keeping nurses at work: a duration analysis.
AB  - A shortage of nurses is currently a problem in several countries, and an
      important question is therefore how one can increase the supply of nursing
      labour. In this paper, we focus on the issue of nurses leaving the public health
      sector by utilising a unique data set containing information on both the supply
      and demand side of the market. To describe the exit rate from the health sector
      we apply a semi-parametric hazard rate model. In the estimations, we correct for
      unobserved heterogeneity by both a parametric (Gamma) and a non-parametric
      approach. We find that both wages and working conditions have an impact on
      nurses' decision to quit. Furthermore, failing to correct for the fact that
      nurses' income partly consists of compensation for inconvenient working hours
      results in a considerable downward bias of the wage effect.

PMID- 12203754
TI  - An econometric analysis of the mental-health effects of major events in the life
      of older individuals.
AB  - Major events in the life of an older individual, such as retirement, a
      significant decrease in income, death of the spouse, disability, and a move to a
      nursing home, may affect the mental-health status of the individual. For example,
      the individual may enter a prolonged depression. We investigate this using unique
      longitudinal panel data that track labor market behavior, health status, and
      major life events, over time. To deal with endogenous aspects of these events we
      apply fixed effects estimation methods. We find some strikingly large effects of
      certain events on the occurrence of depression. We relate the results to the
      health care and labor market policy towards older individuals.

PMID- 12203755
TI  - How important are tobacco prices in the propensity to start and quit smoking? An
      analysis of smoking histories from the Spanish National Health Survey.
AB  - This paper presents an econometric analysis of the effect of policy instruments
      such as prices, restrictions to use and health warnings on the decisions to start
      and quit smoking. The duration up to starting and up to quitting is represented
      with several parametric models for the hazard function, and statistical tests are
      used to choose the best specification. The estimates reveal that prices have a
      very weak effect on the duration up to starting. On the contrary, the duration up
      to quitting is shortened by increases in the prices of the cheapest varieties of
      cigarettes in the Spanish market. This evidence suggests specific directions for
      change in the structure of tobacco taxes.

PMID- 12203756
TI  - Vertical and horizontal aspects of socio-economic inequity in general
      practitioner contacts in Scotland.
AB  - Health status varies across socio-economic groups and health status is generally
      assumed to predict health care needs. Therefore the need for health care varies
      across socio-economic groups, and studies of equity in the distribution of health
      care between socio-economic groups must compare levels of utilisation with levels
      of need. Economic studies of equity in health care generally assume that health
      care needs can be derived from the current health-health care relationship. They
      therefore do not consider whether the current health-health care relationship is
      (vertically) equitable and the focus is restricted to horizontal inequity. This
      paper proposes a framework for incorporating the implications of vertical
      inequity for the socio-economic distribution of health care. An alternative to
      the current health-health care relationship is proposed using a restriction on
      the health-elasticity of health care. The health-elasticity of general
      practitioner contacts in Scotland is found to be generally negative, but positive
      at low levels of health status. Pro-rich estimates of horizontal inequity and
      vertical inequity are obtained but neither is statistically significant. Further
      analysis demonstrates that the magnitude of vertical inequity in health care may
      be larger than horizontal inequity.

PMID- 12203757
TI  - Bayesian estimation, simulation and uncertainty analysis: the cost-effectiveness
      of ganciclovir prophylaxis in liver transplantation.
AB  - This paper demonstrates the usefulness of combining simulation with Bayesian
      estimation methods in analysis of cost-effectiveness data collected alongside a
      clinical trial. Specifically, we use Markov Chain Monte Carlo (MCMC) to estimate
      a system of generalized linear models relating costs and outcomes to a disease
      process affected by treatment under alternative therapies. The MCMC draws are
      used as parameters in simulations which yield inference about the relative cost
      effectiveness of the novel therapy under a variety of scenarios. Total parametric
      uncertainty is assessed directly by examining the joint distribution of simulated
      average incremental cost and effectiveness. The approach allows flexibility in
      assessing treatment in various counterfactual premises and quantifies the global
      effect of parametric uncertainty on a decision-maker's confidence in adopting one
      therapy over the other.

PMID- 12203758
TI  - Cardiac MRI: recent progress and continued challenges.
AB  - Cardiac MRI continues to develop and advance. MRI accurately depicts cardiac
      structure, function, perfusion, and myocardial viability with an overall capacity
      unmatched by any other single imaging modality. MRI is an accepted and widely
      utilized tool for cardiovascular research. Its clinical use has been limited, but
      is increasing because of its proven clinical efficacy, the proliferation of
      cardiac-capable MRI systems, and the development of improved pulse sequences. The
      following article reviews the landmark developments in this field, with an
      emphasis on recent progress in the evaluation of ischemic or acquired heart
      disease.

PMID- 12203759
TI  - BOLD fMRI of the visual cortex: quantitative responses measured with a graded
      stimulus at 1.5 Tesla.
AB  - PURPOSE: To measure and quantitatively characterize an activity generated by the
      neurons of the visual cortex (VC) in response to graded luminous intensity
      contrast stimuli using a 1.5 Tesla scanner. MATERIALS AND METHODS: Functional
      magnetic resonance imaging (fMRI) of the vc with the intrinsic blood oxygenation
      level dependent (BOLD) mechanism was performed by using a paradigm with a 5 x 5
      flashing checkerboard pattern flickering eight times per second at eight
      luminance contrasts presented in a randomized order. The changes of the luminance
      contrast were obtained by varying the luminance intensity of the white
      checkerboard squares. Each of eight trials, corresponding to eight luminance
      contrasts, consisted of six "rest" and six "activation" epochs, repeated five
      times, amounting to 60 measurement periods per trial. During each epoch, 10
      contiguous oblique axial-to-coronal slices covering the calcarine fissure region
      and parallel to a line through the anterior-posterior commissure (AC-PC) markers
      were acquired using a gradient-recalled echo planar imaging (GRE-EPI) sequence.
      RESULTS: The measurements showed changes in the activation extent in the VC
      following the stimulus' rising luminance intensity contrast. In addition, the
      fMRI signal in those activated areas present throughout all eight trials,
      referred to as "common" voxels in this report, showed an increasing trend as a
      function of the rising luminance intensity contrast. CONCLUSION: These results
      suggest that the processes of the neuronal recruitment that affects the extent
      and number of activated neurons, and the neuronal enhancement that defines the
      magnitude of the neuronal activation are dependent on the luminance intensity
      contrast. These changes can be visualized and quantified using BOLD fMRI at 1.5
      Tesla.

PMID- 12203760
TI  - FAIR and dynamic susceptibility contrast-enhanced perfusion imaging in healthy
      subjects and stroke patients.
AB  - PURPOSE: To compare dynamic susceptibility contrast-enhanced magnetic resonance
      imaging (DSC-MRI) and the flow-sensitive alternating inversion recovery (FAIR)
      technique for measuring brain perfusion. MATERIALS AND METHODS: We investigated
      12 patients with acute stroke, and 10 healthy volunteers with FAIR and DSC maps
      of regional cerebral blood volume (rCBV), mean transit time (MTT), and regional
      cerebral blood flow (rCBF). RESULTS: In volunteers good gray/white-matter
      contrast was observed in FAIR, rCBF, and rCBV maps. Regions with high signal
      intensities in FAIR matched well with high values of rCBV and rCBF. In ischemic
      stroke patients a high correlation (r = 0.78) of the ipsi- to contralateral
      signal intensity ratios in FAIR and rCBF was observed in areas with perfusion
      abnormalities. In contrast, FAIR and rCBV (r = 0.50), and FAIR and MTT (r = 
      0.22) correlated only modestly. Furthermore, FAIR and rCBF demonstrated similar
      sizes of perfusion abnormality. CONCLUSION: This study demonstrates for the first
      time that FAIR and rCBF depict similar relations of perfusion in ischemic stroke
      patients and healthy subjects.

PMID- 12203761
TI  - Study of laser ablation in the in vivo rabbit brain with MR thermometry.
AB  - PURPOSE: To investigate the peak temperature and thermal dose (T(43)) as tissue
      damage indicators for thermal therapy. MATERIALS AND METHODS: The proton resonant
      frequency (PRF) shift thermal coefficient was calibrated on six in vivo rabbit
      brains during interstitial laser ablation. The peak temperature and T(43) were
      correlated with the lesion boundary observed on T2-weighted spin-echo (SE) MRI at
      4 hours post-heating in seven thermal lesions using direct MR measurement and
      analysis based on a binary discriminate model. RESULTS: The peak temperature and
      T(43) were 48.3 +/- 1.7 degrees C and 191 +/- 219 minutes, respectively, from the
      direct MR measurement. The values derived by the binary discriminate analysis
      were 47.8 +/- 2.2 degrees C and 28 +/- 41 minutes, respectively. CONCLUSION: Our
      results suggest that tissue damage in rabbit brain 4 hours after thermal ablation
      can be predicted reliably from a threshold temperature of approximately 48
      degrees C.

PMID- 12203762
TI  - Sequential diffusion-weighted magnetic resonance imaging study of
      lysophosphatidyl choline-induced experimental demyelinating lesion: an animal
      model of multiple sclerosis.
AB  - PURPOSE: To differentiate the surrounding edema from the focal demyelinating
      lesion during the early phase of the lesion using an apparent diffusion
      coefficient (ADC), and to monitor the changes in ADCs during the complete
      progression of a lysophosphatidyl choline (LPC)-induced experimental
      demyelinating lesion, an animal model of multiple sclerosis (MS). MATERIAL AND
      METHODS: Eighteen rats divided into two groups-demyelinating lesion (group I, N =
      12) and vehicle group (saline injected; group II, N = 6)-were studied. A 0.2
      microl quantity of 1% LPC solution in isotonic saline was injected in the rat
      brain internal capsule (IC) area to create the demyelinating lesion. Six rats
      were used exclusively for histology. Diffusion-weighted (DW) images were acquired
      at different diffusion weightings on the 3rd, 5th, 10th, 15th, and 20th days
      after LPC injection. ADC was measured from three regions of interest (ROIs)
      within the IC: focal demyelinating lesion (area A), surrounding area of the
      lesion (area B), and contralateral IC area (area C). RESULTS: Histology revealed
      demyelination of the IC area during the early phase of lesion progression up to
      day 10 and remyelination thereafter. Elevated ADCs were observed for the
      surrounding edematous area (area B), compared to the focal demyelinating lesion
      (area A) during the early phase of the demyelination process, while substantial
      reduction of ADCs was noticed during remyelination for both regions. CONCLUSION:
      Measurement of ADC showed clear differentiation of the surrounding edema from the
      LPC-induced focal demyelinating lesion in rats, especially during the early phase
      of the lesion progression.

PMID- 12203763
TI  - Proton MRS in Kennedy disease: absolute metabolite and macromolecular
      concentrations.
AB  - PURPOSE: To investigate whether glutamine and glutamate (Glx) were elevated in
      Kennedy Disease (KD), and whether pathological proteins were spectroscopically
      visible as altered macromolecular (MM) resonances. MATERIALS AND METHODS: Ten
      patients with KD and twelve healthy volunteers were investigated using a
      stimulated echo acquisition mode (STEAM) spectroscopy sequence with metabolite
      nulling. RESULTS: The concentrations of Glx remained unchanged in KD. An
      increased myo-inositol (Ins), and elevated MM at 0.9 ppm were found within the
      motor area. The N-acetyl-aspartate (NAA)/creatine (Cr) ratio was negatively
      correlated to the number of cytosine adenosine guanine (CAG) repeats in the motor
      area. CONCLUSION: The elevated MM at 0.9 ppm may be attributed to a
      pathologically altered protein in KD. Additionally, the changes of Ins point to a
      clinically unexpected involvement of the motor cortex. The correlation of NAA/Cr
      with the number of CAG repeats indicates a link between metabolites and genetic
      failure.

PMID- 12203764
TI  - Comparison of first-pass Gd-DOTA and FAIRER MR perfusion imaging in a rabbit
      model of pulmonary embolism.
AB  - PURPOSE: To compare the sensitivity of contrast-enhanced magnetic resonance
      imaging (MRI) and arterial spin labeling to perfusion deficits in the lung.
      MATERIALS AND METHODS: A rabbit model of pulmonary embolism was imaged with both
      flow-sensitive alternating inversion recovery with an extra radiofrequency pulse
      (FAIRER) arterial spin labeling and Gd-DOTA enhanced MRI. The signal-to-noise
      ratio (SNR) was measured in the area of the perfusion deficit and the normal lung
      for both techniques. RESULTS: The defect was readily visible in all images. The
      normal lung had an average of 3.8 +/- 1.2 times the SNR of the unperfused lung
      with the arterial spin labeling technique, and approximately 13.7 +/- 3.3 times
      the SNR with the contrast-enhanced technique. CONCLUSION: Gd-DOTA enhanced MRI
      provides higher SNR in pulmonary perfusion imaging; however, arterial spin
      labeling is also adequate and may be used when repeated studies are indicated.

PMID- 12203765
TI  - Differentiation of clinically benign and malignant breast lesions using diffusion
      weighted imaging.
AB  - PURPOSE: To evaluate the value of diffusion-weighted imaging (DWI) in
      distinguishing between benign and malignant breast lesions. MATERIALS AND
      METHODS: Fifty-two female subjects (mean age = 58 years, age range = 25-75 years)
      with histopathologically proven breast lesions underwent DWI of the breasts with
      a single-shot echo-planar imaging (EPI) sequence using large b values. The
      computed mean apparent diffusion coefficients (ADCs) of the breast lesions and
      cell density were then correlated. RESULTS: The ADCs varied substantially between
      benign breast lesions ((1.57 +/- 0.23) x 10(-3) mm(2)/second) and malignant
      breast lesions ((0.97 +/- 0.20) x 10(-3) mm(2)/second). In addition, the mean
      ADCs of the breast lesions correlated well with tumor cellularity (P < 0.01, r = 
      0.542). CONCLUSION: The ADC would be an effective parameter in distinguishing
      between malignant and benign breast lesions. Further, tumor cellularity has a
      significant influence on the ADCs obtained in both benign and malignant breast
      tumors.

PMID- 12203766
TI  - Radial fast spin-echo method for T2-weighted imaging and T2 mapping of the liver.
AB  - PURPOSE: To evaluate a multishot radial fast-spin echo (RAD-FSE) method developed
      to improve the quality of abdominal T2-weighted imaging as well as the
      characterization of focal liver lesions. MATERIALS AND METHODS: The RAD-FSE
      sequence used in this work consisted of a preparatory period followed by a short
      echo train (ETL = 16). A novel radial k-space trajectory was used to minimize
      streaking artifacts due to T2 variations and motion. Small diffusion gradients (b
      = 1.2 mm/s(2)) were used to improve flow suppression. The quality of images
      obtained with RAD-FSE was compared to multishot 2DFT fast spin-echo (2DFT-FSE)
      and half-Fourier acquisition single-shot turbo-spin-echo (HASTE) images using
      data from 16 patients. A postprocessing algorithm was used to generate multiple
      high-resolution images (at different effective TE values) as well as a T2 map
      from a single RAD-FSE data set. The T2 maps were used to differentiate malignant
      from benign lesions for a set of 33 lesions ranging from 0.8-194 cm(3). RESULTS:
      RAD-FSE produces high-resolution images of the liver in a breath-hold without the
      motion artifacts of 2DFT-FSE methods, and without the blurriness and loss of
      small lesion detectability of HASTE. The inclusion of diffusion weighting in RAD
      FSE decreases the signal from blood in hepatic vessels, which improves lesion
      visualization. The T2 values obtained by postprocessing a single RAD-FSE data set
      can differentiate malignant from benign lesions. The mean T2 values obtained for
      malignancies, hemangiomas, and cysts are 108 +/- 30 msec, 240 +/- 14 msec, and
      572 +/- 334 msec, respectively. CONCLUSION: These results indicate that RAD-FSE
      produces abdominal images of higher quality than 2DFT-FSE and HASTE. In addition,
      lesions can be characterized using T2 maps generated from a single RAD-FSE data
      set.

PMID- 12203767
TI  - Evaluation of a new ultrasmall superparamagnetic iron oxide contrast agent
      Clariscan, (NC100150) for MRI of renal perfusion: experimental study in an animal
      model.
AB  - PURPOSE: To determine the diagnostic value of a new ultrasmall superparamagnetic
      iron oxide Clariscan, (NC100150) for the evaluation of renal perfusion in an
      animal model using a 3D-FFE-EPI sequence. MATERIALS AND METHODS: Four groups of
      four rabbits each were imaged after bolus injection of NC100150, using a 1.5 T MR
      system (Gyroscan ACS-NT). T2*w MR images in the coronal plane were acquired over
      60 seconds with an echo-shifted 3D-FFE-EPI sequence (TR/TE/alpha = 18/25 msec/8
      degrees ). Data were transferred to a workstation and converted into
      concentration curves. Based on the fitted concentration time curves, parameter
      maps were calculated pixelwise: bolus arrival time (T0), time-to-peak (TTP), mean
      transit time (MTT), and relative bolus volume (rBV). Maximum signal decrease was
      determined with respect to the baseline value. RESULTS: Mean MTT increased from
      4.2 seconds at a dose of 0.25 mg to 5.9 seconds at 1.0 mg (P < .0001). The
      maximum signal decrease was observed at 0.75 mg, corresponding to 85% of the
      baseline value. Transit times of the contrast bolus were accurately calculated
      for the cortex and the outer medulla, but at the level of the inner medulla no
      arterial flow profile was identified. No significant difference between the
      cortex and the outer medulla was found for either T0 or rBV, but medullar TTP and
      MTT were prolonged with regard to cortical TTP and MTT (6.3 seconds vs. 5.7
      seconds, P < .001; 5.7 seconds vs. 4.2 seconds, P < .0001). CONCLUSION: The
      employed intravascular contrast agent is well suited to assess renal perfusion.
      By the use of a T2*w3D perfusion sequence, cortical and medullar transit times
      can be quantified and physiologic information on regional perfusion differences
      can be obtained.

PMID- 12203768
TI  - In vivo measurement of the apparent diffusion coefficient in normal and malignant
      prostatic tissues using echo-planar imaging.
AB  - PURPOSE: To measure for the first time the apparent diffusion coefficient (ADC)
      values in anatomical regions of the prostate for normal and patient groups, and
      to investigate its use as a differentiating parameter between healthy and
      malignant tissue within the patient group. MATERIALS AND METHODS: Single-shot
      diffusion-weighted echo-planar imaging (DW-EPI) was used to measure the ADC in
      the prostate in normal (N = 7) and patient (N = 19) groups. The spin-echo images
      comprised 96 x 96 pixels (field of view of 16 cm, TR/TE = 4000/120 msec) with six
      b-factor values ranging from 64 to 786 seconds/mm(2). RESULTS: The ADC values
      averaged over all patients in non-cancerous and malignant peripheral zone (PZ)
      tissues were 1.82 +/- 0.53 x 10(-3) (mean +/- SD) and 1.38 +/- 0.52 x 10(-3)
      mm(2)/second, respectively (P = 0.00045, N = 17, paired t-test). The ADC values
      were found to be higher in the non-cancerous PZ (1.88 +/- 0.48 x 10(-3)) than in
      healthy or benign prostatic hyperplasia central gland (BPH-CG) region (1.62 +/-
      0.41 x 10(-3)). For the normal group, the mean values were 1.91 +/- 0.46 x 10(-3)
      and 1.63 +/- 0.30 x 10(-3) mm(2)/second for the PZ and CG, respectively (P =
      0.011, N = 7). Significant overlap exists between individual values among all
      tissue types. Furthermore, ADC values for the same tissue type showed no
      statistically significant difference between the two subject groups. CONCLUSION:
      ADC is quantified in the prostate using DW-EPI. Values are lower in cancerous
      than in healthy PZ in patients, and in BPH-CG than PZ in volunteers.

PMID- 12203769
TI  - Simultaneous real-time visualization of the catheter tip and vascular anatomy for
      MR-guided PTA of iliac arteries in an animal model.
AB  - PURPOSE: To examine the feasibility of simultaneous MR real-time active tip
      tracking and near real-time depiction of the vascular anatomy for percutaneous
      angioplasty of iliac arteries under MR guidance. MATERIALS AND METHODS: Nine
      surgically created stenoses of external iliac arteries in pigs were dilated with
      MR-compatible balloon catheters (Cordis, Roden, The Netherlands). These catheters
      were equipped with a microcoil for active tracking of the catheter tip with an in
      plane update rate of 10 positions per second. The procedures were performed on an
      interventional 1.5 T Gyroscan ACS-NT scanner (Philips, Best, The Netherlands).
      Real-time calculation of images acquired by radial k-space filling was performed
      on a specially designed backprojector exploiting the sliding window
      reconstruction technique (Philips Research Laboratories, Hamburg, Germany). The
      image update rate was 20 frames per second using a radial gradient-echo technique
      (TR = 12 msec, TE = 3.3 msec, 300 radials). MR angiography and X-ray digital
      subtraction angiography on the X-ray system positioned in-line next to the
      interventional MR system served as control for the angioplasty results. RESULTS:
      Real-time guidance and positioning of the balloon catheters was possible. The
      actual position of the catheter tip was indicated in the MR images without any
      time delay for the reconstruction of the anatomical MR images, which were updated
      with a rate of 20 frames per second. This yielded a combination of a roadmap and
      fluoroscopy image, in which the catheter position and the anatomical background
      image both were continuously updated in real time. Six out of nine stenoses were
      successfully dilated. The effects of the angioplasty could be visualized by the
      real-time MR technique, as was proven by X-ray digital subtraction angiography.
      CONCLUSION: Active tip tracking simultaneous with MRI of the vascular anatomy
      both in real time-is possible with the applied technique, enabling MR-guided
      percutaneous dilatation (PTA) of iliac arteries.

PMID- 12203770
TI  - Imaging articular cartilage defects in the ankle joint with 3D fat-suppressed
      echo planar imaging: comparison with conventional 3D fat-suppressed gradient echo
      imaging.
AB  - PURPOSE: To shorten the examination time for articular cartilage imaging, using a
      recently developed three-dimensional (3D) multishot echo planar imaging (EPI)
      sequence with fat saturated (FS), compared to a conventional 3D fat-saturated
      spoiled gradient echo sequence (3D FS GRE). MATERIAL AND METHODS: There were 32
      consecutive patients with ankle joint disorders who underwent magnetic resonance
      imaging (MRI) in a 1.0-T unit. Hyaline cartilage was imaged with a 3D FS EPI
      sequence and a 3D FS GRE sequence. Image assessment criteria included lesion
      conspicuity, contrast between different types of normal tissue, and image
      artifacts. In addition, contrast-to-noise ratios (CNRs) of cartilage vs. joint
      fluid and bone marrow were measured. RESULTS: The 3D FS EPI sequence provided a
      high CNR between cartilage and subchondral bone, similar to that of the 3D FS GRE
      sequence. The CNR between cartilage and effusion was significantly lower on the
      3D EPI sequence due to the higher signal intensity of fluid. Both sequences were
      equal in lesion detection ability. The image quality of the 3D FS GRE sequence
      was slightly higher than that of the 3D FS EPI, but the difference was not
      statistically significant. CONCLUSION: We conclude that the 3D FS EPI sequence is
      comparable to the 3D FS GRE sequence in the detection of cartilage lesions, with
      the additional advantage of reduction in scan time by a factor of 4.

PMID- 12203771
TI  - Initial experience with the intravascular contrast agent NC100150-injection
      (Clariscan) for breath-hold and navigator-gated magnetic resonance coronary
      artery imaging.
AB  - PURPOSE: To examine magnetic resonance coronary artery imaging after NC100150
      Injection. MATERIALS AND METHODS: Breath-hold and navigator-gated images were
      acquired in five patients. RESULTS: Breath-hold image quality, coronary artery
      fat SDNR, and coronary artery SNR improved. Respiratory artifacts due to reduced
      liver signal intensity degraded navigator-gated image quality. CONCLUSION:
      NC100150-Injection improves breath-hold coronary artery imaging. Navigator-gated
      acquisitions should use techniques that are insensitive to T2* effects.

PMID- 12203773
TI  - The role of Alu repeat clusters as mediators of recurrent chromosomal aberrations
      in tumors.
AB  - There is increasing evidence for the involvement of repetitive DNA sequences as
      facilitators of some of the recurrent chromosomal rearrangements observed in
      human tumors. The high densities of repetitive DNA, such as Alu elements, at some
      chromosomal translocation breakpoint regions has led to the suggestion that these
      sequences could provide hot spots for homologous recombination, and could mediate
      the translocation process and elevate the likelihood of other types of
      chromosomal rearrangements taking place. The Alu core sequence itself has been
      suggested to promote DNA strand exchange and genomic rearrangement, and it has
      striking sequence similarity to chi (which has been shown to stimulate recBCD
      mediated recombination in Escherichia coli). Alu repeats have been shown to be
      involved in the generation of many constitutional gene mutations in meiotic
      cells, attributed to unequal homologous recombination and consequent deletions
      and/or duplication events. It has recently been demonstrated that similar
      deletion events can take place in neoplasia because several types of leukemia
      associated chromosomal rearrangements frequently have submicroscopic deletions
      immediately adjacent to the translocation breakpoint regions. Significantly,
      these types of deletions appear to be more likely to take place when the regions
      subject to rearrangement contain a high density of Alu repeats. With the
      completion of the Human Genome Project, it will soon be possible to create more
      comprehensive maps of the distribution and densities of repetitive sequences,
      such as Alu, throughout the genome. Such maps will offer unique insights into the
      relative distribution of cancer translocation breakpoints and the localization of
      clusters of repetitive DNA.

PMID- 12203772
TI  - In vivo animal functional MRI: improved image quality with a body-adapted mold.
AB  - PURPOSE: To reduce functional magnetic resonance imaging (fMRI) susceptibility
      distortion at the air/tissue interphase in animal experiments. MATERIALS AND
      METHODS: We investigated the applicability of a body-adaptable flexible mold
      consisting of a fast-setting alginate. This technique was implemented for
      subcutaneous growing tumors in rats and for the brains of monkeys. RESULTS: The
      T(2)*-weighted gradient-echo, echo-planar imaging (GE-EPI) data obtained with the
      body-adapted mold showed a reduction of susceptibility artifacts and improved
      image quality. With both rat tumor and monkey brain, an optimized match with the
      anatomical T(1) images was possible. CONCLUSION: The present mold methodology is
      a rapid, easy, and inexpensive way to reduce magnetic susceptibility during
      animal GE-EPI.

PMID- 12203774
TI  - Localization of the 17q breakpoint of a constitutional 1;17 translocation in a
      patient with neuroblastoma within a 25-kb segment located between the ACCN1 and
      TLK2 genes and near the distal breakpoints of two microdeletions in
      neurofibromatosis type 1 patients.
AB  - We have constructed a 1.4-Mb P1 artificial chromosome/bacterial artificial
      chromosome (PAC/BAC) contig spanning the 17q breakpoint of a constitutional
      translocation t(1;17)(p36.2;q11.2) in a patient with neuroblastoma. Three 17q
      breakpoint-overlapping cosmids were identified and sequenced. No coding sequences
      were found in the immediate proximity of the 17q breakpoint. The PAC/BAC contig
      covers the region between the proximally located ACCN1 gene and the distally
      located TLK2 gene and SCYA chemokine gene cluster. The observation that the 17q
      breakpoint region could not be detected in any of the screened yeast artificial
      chromosome libraries and the localization of the 17q breakpoint in the vicinity
      of the distal breakpoints of two microdeletions in patients with
      neurofibromatosis type 1 suggest that this chromosomal region is genetically
      unstable and prone to rearrangements.

PMID- 12203775
TI  - Epigenetic control of the E-cadherin gene (CDH1) by CpG methylation in colectomy
      samples of patients with ulcerative colitis.
AB  - E-cadherin belongs to the cadherin family of calcium-dependent cell-adhesion
      molecules. The cadherins play an essential role in biological processes such as
      ordering of cell sorting, migration, and differentiation, and their
      malfunctioning is connected with neoplasia. Neoplastic progression in patients
      with chronic ulcerative colitis is characterized by the development of epithelial
      dysplasia. Transcriptional silencing of tumor-suppressor genes by promoter
      methylation has been observed in different types of human cancers and dysplasia.
      To explore the mode of E-cadherin regulation, 156 biopsy samples from 26 patients
      with long-standing ulcerative colitis were screened. To detect the methylation
      status of our samples, a methylation-specific PCR was applied. Methylation of the
      E-cadherin (CDH1) promoter was detected in 93% of the patients with dysplastic
      biopsy samples, in contrast to only 6% of the patients without dysplasia (P <
      0.001). We also examined the level of synthesis of E-cadherin protein by
      immunohistochemical staining in different paraffin-embedded samples of dysplastic
      and non-dysplastic origin in a subset of our patients. Samples with dysplasia
      displayed reduced levels, whereas samples without dysplasia revealed normal E
      cadherin protein synthesis. These results show that the E-cadherin promoter is
      subjected to epigenetic control in colorectal ulceration. Obviously, this event
      may play an important role in the progression from chronic inflammation to
      colorectal cancer. For this reason, methylation of the CDH1 promoter is an
      attractive new biomarker for detecting ulcerative colitis patients with a high
      risk for developing colorectal cancers.

PMID- 12203776
TI  - Multicolor COBRA-FISH analysis of chronic myeloid leukemia reveals novel cryptic
      balanced translocations during disease progression.
AB  - During the initial indolent chronic phase of chronic myeloid leukemia (CML), the
      t(9;22)(q34;q11), resulting in the Philadelphia chromosome (Ph), is usually the
      sole cytogenetic anomaly, but as the disease progresses into the accelerated
      phase (AP), and eventually into aggressive blast crisis (BC), secondary
      aberrations, mainly unbalanced changes such as +8, i(17q), and +Ph, are frequent.
      To date, molecular genetic studies of CML BC have mainly focused on alterations
      of well-known tumor-suppressor genes (e.g., TP53, CDKN2A, and RB1) and oncogenes
      (e.g., RAS and MYC), whereas limited knowledge is available about the molecular
      genetic correlates of the unbalanced chromosomal abnormalities. Balanced
      secondary changes are rare in CML AP/BC, but it is not known whether cryptic
      chromosomal translocations, generating fusion genes, may be responsible for
      disease progression in a subgroup of CML. To address this issue, we used
      multicolor combined binary ratio fluorescence in situ hybridization (FISH), which
      allows the simultaneous visualization of all 24 chromosomes in different colors,
      verified by locus-specific FISH in a series of 33 CML cases. Two cryptic balanced
      translocations, t(7;17)(q32-34;q23) and t(7;17)(p15;q23), were found in two of
      the five cases showing the t(9;22) as the only cytogenetic change. Using several
      BAC clones, the breakpoints at 17q23 in both cases were mapped within a 350-kb
      region. In the case with the 7p15 breakpoint, a BAC clone containing the HOXA
      gene cluster displayed a split signal, suggesting a possible creation of a fusion
      gene involving a member of the HOXA family. Furthermore, one case with a
      partially cryptic t(9;11)(p21-22;q23) and an MLL rearrangement as well as a
      previously unreported t(3;10)(p22;p12-13) were identified. Altogether, a refined
      karyotypic description was achieved in 12 (36%) of the 33 investigated cases,
      illustrating the value of using multicolor FISH for identifying pathogenetically
      important aberrations in CML AP/BC.

PMID- 12203777
TI  - Chromosomal analysis of hepatic adenoma and focal nodular hyperplasia by
      comparative genomic hybridization.
AB  - Hepatic adenoma (HA) and focal nodular hyperplasia (FNH) are two common non
      malignant tumors of the liver. Genomic analysis on these benign lesions may shed
      light on the genetic mechanism underlying liver carcinogenesis. We used
      comparative genomic hybridization (CGH) to evaluate genomic changes in eight
      cases of HA and six cases of FNH, obtained by surgical procedures; the resulting
      chromosomal aberration profiles were analyzed together with their pathological
      and clinical manifestations. We found consistent chromosomal lesions associated
      with both non-malignant hepatic tumors. The overall genomic abnormalities in HA
      and FNH were much less obvious than those in hepatocellular carcinoma (HCC).
      Among these limited changes, frequent gains were located on chromosomal arms 1q
      (50%), 17q (50%), 1p (38%), and 11q (38%) in HA, and on 11q (50%), 9q (33%), 17q
      (33%), and 22q (33%) in FNH. Gains outnumbered losses, and HA contained more CGH
      abnormalities than did FNH. Interestingly, CGH alteration hotspots found in HA,
      but not in FNH, appeared largely to coincide with common genomic lesions of
      cancerous HCC, suggesting an interesting relationship along the tumorigenesis
      pathway of HA and HCC.

PMID- 12203778
TI  - Comparative genomic hybridization analysis of primary cutaneous B-cell lymphomas:
      identification of common genomic alterations in disease pathogenesis.
AB  - To investigate genetic alterations in primary cutaneous B-cell lymphomas
      (PCBCLs), we have analyzed 29 cases of PCBCL. Comparative genomic hybridization
      showed chromosome imbalances (CIs) in 12 cases (41%). The mean number of CIs per
      sample was 2.05 +/- 2.97, with gains (1.48 +/- 2.38) more frequent than losses
      (0.56 +/- 1.40). The common regions of gains were 18/18q (50%), 7/7p (42%), 3/3q
      (33%), 20 (33%), 1p (25%), 12/12q (25%), and 13/13q (25%), whereas loss of 6q was
      frequent (42%). Among the different subsets of PCBCLs, CI was seen in 50% of
      diffuse large-cell lymphomas (DLCLs), 33% of marginal zone lymphomas, and 8% of
      follicle center cell lymphomas and unclassified lymphomas. A similar pattern of
      CI was observed in these lymphomas, but loss of 6q and gains of 3/3q were present
      only in DLCLs. Microarray-based genomic analysis of four DLCL cases identified
      oncogene gains of SAS/CDK4 (12q13.3) in three cases and MYCL1 (1p34.3), MYC
      (8q24), FGFR2 (10q26), BCL2 (18q21.3), CSE1L (20q13), and PDGFB (22q12-13) in two
      cases, whereas losses of AKT1 (14q32.3), IGFR1 (15q25-26), and JUNB (19p13.2)
      were identified in three cases, and losses of FGR (1p36), ESR (6q25.1), ABL1
      (9q34.1), TOP2A (17q21-22), ERBB2 (17q21.2), CCNE1 (19q13.1), and BCR (22q11)
      were each identified in two cases. In addition, real-time-polymerase chain
      reaction detected amplification of BCL2 in 5 of 29 cases. These findings suggest
      that there are complex but consistent genetic alterations associated with the
      pathogenesis of PCBCLs.

PMID- 12203779
TI  - Chromosome arm 16q in Wilms tumors: unbalanced chromosomal translocations, loss
      of heterozygosity, and assessment of the CTCF gene.
AB  - Chromosome arm 16q is a common site of loss of heterozygosity (LOH) in Wilms
      tumors (WTs). The mechanism and consequences of 16q LOH are not known, but the
      CTCF gene, in band 16q22, is a candidate target gene. CTCF protein binds to DNA
      upstream of the H19 gene on chromosome band 11p15, and maintains normal
      imprinting of H19 and IGF2. Thus, its loss might predispose to de novo
      methylation of the maternal allele of H19 and loss of imprinting (LOI) of IGF2 in
      WTs. We mapped Chr16 LOH in WTs and correlated this with unbalanced chromosomal
      translocations and histopathology. We also analyzed the CTCF gene for its mRNA
      and protein expression and DNA sequence, and we investigated correlations with
      methylation of H19(mat). In our series, unbalanced t(1;16) chromosomal
      translocations were a major pathway for Chr16 loss of heterozygosity, and this
      LOH was correlated significantly with tumor anaplasia. CTCF mapped in the minimal
      region of Chr16 LOH. However, we found no correlation between Chr16 LOH, or loss
      of CTCF mRNA or protein, and methylation of H19(mat). Some WTs contained reduced
      amounts of CTCF protein, but among these were cases with and without H19(mat)
      methylation. Rare WTs with simultaneous 16q LOH and H19(mat) methylation lacked
      CTCF mutations. These data argue against the CTCF gene as a target of Chr16 LOH
      in WTs, but leave open the possibility that post-transcriptional loss of CTCF
      protein may account for some instances of LOI.

PMID- 12203780
TI  - Sequential changes of the DMBT1 expression and location in normal lung tissue and
      lung carcinomas.
AB  - Deleted in Malignant Brain Tumors 1 (DMBT1) at chromosome region 10q25.3-q26.1
      has been proposed as a candidate tumor-suppressor gene for brain, digestive
      tract, and lung cancer. Recent studies on its expression in lung cancer have led
      to divergent results and have raised a controversial discussion. Moreover, DMBT1
      has been implicated with epithelial protection in the respiratory tract. We thus
      wondered how a loss of its expression could be related to carcinogenesis in the
      lung. To address these issues, we investigated the DMBT1 expression and location
      in the normal lung and lung cancer. By reverse-transcription PCR, a down
      regulation of the DMBT1 expression in lung cancer cell lines is commonly
      detected. Immunohistochemical studies in situ demonstrate that there are also low
      steady-state levels of DMBT1 in the normal respiratory epithelium. However, an up
      regulation takes place in the tumor-flanking epithelium and upon respiratory
      inflammation. Lung carcinomas show increased DMBT1 expression compared to that of
      undiseased lung tissue, but decreased DMBT1 levels compared to that of tumor
      flanking and inflammatory tissue. A switch from a lumenal secretion to a
      secretion to the extracellular matrix takes place during lung carcinogenesis. Our
      data may resolve the controversial discussion on its expression in lung
      carcinomas. We hypothesize that the changes of the DMBT1 expression and location
      do reflect a time course that may point to possible mechanisms for its role in
      epithelial cancer.

PMID- 12203781
TI  - Identification of the small interstitial deletion at chromosome band 1p34-p35 and
      its association with poor outcome in oligodendroglial tumors.
AB  - To narrow down the putative tumor-suppressor gene locus and to assess the
      predictability of clinical courses by genomic alterations, we analyzed 46
      oligodendroglial tumors for loss of heterozygosity (LOH) in the distal region of
      the short arm of chromosome 1. LOH at 1p was found in 43 tumors (93.5%),
      including all 28 oligodendrogliomas, all eight oligo-astrocytomas, six of eight
      anaplastic oligodendrogliomas, and in one of two anaplastic oligo-astrocytomas.
      Thirty-seven tumors showed LOH patterns consistent with a large terminal
      deletion, whereas six tumors showed LOH suggesting interstitial deletions. Our
      data also showed two small regions of overlap at 1p34-p35 (approximately 5.7 Mb)
      and at 1p36.1-p36.2 ( approximately 12 Mb). Among the six tumors with
      interstitial deletion, the proximal region was deleted in five tumors, whereas
      the distal region was deleted in only half of them. Overall, 91% of tumors showed
      deletion including this proximal region. To examine the clinical significance of
      the LOH pattern, the samples were classified into three groups: tumors without 1p
      LOH (Group 1, n = 3), tumors with an interstitial deletion (Group 2, n = 6), and
      tumors with a large terminal deletion (Group 3, n = 37). Both overall and
      progression-free survival of patients in Group 2 was extremely poor compared with
      those included in Group 3 (P = 0.0006 and P = 0.003, respectively). As to the
      clinical response to chemotherapy, nimustine prevented tumor recurrence in Group
      3 (P = 0.034) but not in Group 2. Our results demonstrate that a putative tumor
      suppressor gene(s) in oligodendroglial tumors is localized at 1p34-p35 and that
      small interstitial deletions, in contrast to large terminal deletions, are
      strongly predictive of both chemoresistance and aggressive characteristics of
      these tumors.

PMID- 12203782
TI  - Evidence of a role for the INK4 family of cyclin-dependent kinase inhibitors in
      ovarian granulosa cell tumors.
AB  - Granulosa cell tumors (GCTs) of the ovary are relatively rare and account for <5%
      of all ovarian cancers. The molecular pathogenesis of these tumors is not well
      understood. We tested the hypothesis that cyclin-dependent kinase inhibitors,
      specifically the inhibitors of the cyclin-dependent kinase 4 (INK4) family, are
      targets for altered gene expression in GCTs. The status of RB1, INK4A, INK4B,
      INK4C, INK4D, and ARF in 13 adult and 2 juvenile ovarian GCTs was determined by
      reverse transcription-polymerase chain reaction of total RNA and exon-specific
      sequencing of genomic DNA. Tumors showing loss of INK4A expression were assayed
      further by exon-deletion analysis and methylation-specific PCR. None of the
      juvenile tumors demonstrated altered expression, but 7/12 (58%) adult GCTs lacked
      expression of INK4A, INK4B, or both. In one of these cases, we noted a homozygous
      deletion of the INK4A locus, and in the remaining tumors we found
      hypermethylation of the promoter region, a mechanism that can lead to gene
      inactivation. These data support a role for the INK4 family of CDK inhibitors in
      the biology of GCTs.

PMID- 12203783
TI  - Regulatory subunit type I-alpha of protein kinase A (PRKAR1A): a tumor-suppressor
      gene for sporadic thyroid cancer.
AB  - The tumor-suppressor gene encoding the cyclic AMP-dependent protein kinase A type
      I-alpha regulatory subunit PRKAR1A has been mapped to chromosome 17 (17q22-24)
      and is mutated in Carney complex, a familial neoplasia syndrome that is
      associated with thyroid tumors. Other genes implicated in cyclic nucleotide
      dependent signaling have been investigated in thyroid tumorigenesis. We studied
      protein kinase A (PKA) activity in noninherited follicular thyroid adenomas and
      follicular, papillary, and undifferentiated (anaplastic) thyroid carcinomas. We
      then examined these and additional thyroid tumors for losses of the 17q22-24
      PRKAR1A region, mutations of the PRKAR1A gene, and expression of its peptide
      product. Total PKA activity was markedly increased in carcinomas over that in
      adenomas, whereas the ratio of free vs. total PKA activity was decreased in
      cancer. Consistent with these findings, the 17q22-24 region was frequently lost
      in cancer but not in benign adenomas. A novel inactivating mutation of the
      PRKAR1A gene (leading to premature termination of the predicted protein) was
      found in an aggressive thyroid cancer. The tumor with PRKAR1A gene mutation, as
      well as the tumors with 17q allelic losses, showed decreased PRKAR1A expression
      by immunostaining. We conclude that PRKAR1A, the most abundant regulatory subunit
      of protein kinase A and a principal cyclic AMP-signaling modulator, acts as a
      tumor-suppressor gene in sporadic thyroid cancer. Published 2002 Wiley-Liss, Inc.

PMID- 12203784
TI  - Densely methylated MLH1 promoter correlates with decreased mRNA expression in
      sporadic colorectal cancers.
AB  - It has been reported that MLH1 is silenced by promoter methylation, and that this
      phenomenon is associated with microsatellite instability (MSI) in sporadic
      colorectal cancer (CRC). To clarify the significance of MLH1 promoter methylation
      in sporadic CRC, we examined the correlation between methylation status over the
      entire promoter region and mRNA expression in cases showing high-frequency MSI
      (MSI-H). MLH1 promoter methylation was analyzed using the bisulfite modification
      sequencing in 48 MSI-H cases. We also screened for somatic mutation, loss of
      heterozygosity, and immunohistochemical staining of MLH1. The results showed that
      methylation patterns could be subdivided into three types: methylation of more
      than 80% of the CpG sites analyzed (type 1 methylation), methylation of less than
      20% (type 2 methylation), and methylation mainly in the region 500 to 921 bases
      upstream from the translation start site (type 3 methylation). Of the three
      types, only type 1 methylation correlated with decreased mRNA expression. The
      frequency of type 1 methylation was significantly higher in cases involving the
      proximal colon (66.7%, 18/27) compared to that of the distal colon and rectum
      (23.8%, 5/21, P = 0.004). Immunohistochemical staining of MSI-H cases showed that
      decreased MLH1 was found in 77.1% (37/48). Of the cases with decreased MLH1, type
      1 methylation was present in 59.5% (22/37). Overall, our data suggested that the
      type 1 methylation pattern may affect MLH1 mRNA expression, such that the
      majority of MSI-H cases in sporadic CRC, especially proximal colon cancer,
      exhibited type 1 methylation.

PMID- 12203785
TI  - A novel gene, MDS2, is fused to ETV6/TEL in a t(1;12)(p36.1;p13) in a patient
      with myelodysplastic syndrome.
AB  - ETV6/TEL is the first transcription factor identified that is specifically
      required for hematopoiesis within the bone marrow. This gene has been found to
      have multiple fusion partners of which 16 have been cloned. Fluorescence in situ
      hybridization (FISH) analysis in a patient with myelodysplastic syndrome (MDS)
      revealed a t(1;12)(p36;p13) involving ETV6, with the breakpoint in this gene
      between exon 2 and exon 3. We report here the cloning of a novel ETV6 partner
      located on 1p36.1, involved in the t(1;12). 3' RACE-PCR from RNA identified a
      novel sequence fused to exon 2 of ETV6. Database searches localized this sequence
      in a bacterial artificial chromosome (BAC) mapped to 1p36 by fingerprint
      analysis. This result was confirmed by FISH using this BAC as probe. 5' and 3'
      RACE experiments with primers from this novel sequence were carried out on RNA
      from a healthy donor and identified a novel full-length mRNA, which we named MDS2
      (myelodysplastic syndrome 2). RT-PCR experiments were performed on a panel of
      human cDNAs to analyze the expression pattern of this gene and they revealed four
      splicing variants. RT-PCR analysis showed that ETV6-MDS2, but not the reciprocal
      MDS2-ETV6 fusion transcript, was expressed in the bone marrow of the patient. The
      product of the ETV6-MDS2 fusion transcript predicts a short ETV6 protein
      containing the first 54 amino acids of ETV6 plus four novel amino acids, lacking
      both the PTN and the DNA-binding domains. Possible mechanisms to account for the
      development of MDS in this patient are discussed.

PMID- 12203786
TI  - Loss of genetic material is more common than gain in acute myeloid leukemia with
      complex aberrant karyotype: a detailed analysis of 125 cases using conventional
      chromosome analysis and fluorescence in situ hybridization including 24-color
      FISH.
AB  - Patients with acute myeloid leukemia (AML) and a complex aberrant karyotype have
      a poor outcome despite intensive antileukemic treatment. The aim of this study
      was to analyze in detail the genetic abnormalities in this subgroup of AML.
      Therefore, 125 AML cases with complex aberrant karyotype detected by G-banding
      were examined in addition with 24-color FISH and FISH with locus-specific probes
      for EGR1 (5q31), D7S522 (7q31), and TP53 (17p13), given that these regions are
      known to be commonly deleted in AML with a complex aberrant karyotype. The number
      of chromosome abnormalities per case varied from 3 to 30 (median 10). A gain of a
      whole chromosome was observed 131 times, with +8 (n = 30), +10 (n = 11), and +22
      (n = 10) being the most frequent trisomies. A loss of a whole chromosome occurred
      128 times. The chromosomes most often lost were 7 (n = 25), 18 (n = 24), and 17
      (n = 17). Structural aberrations, leading to a gain or loss of chromosomal
      material, were detected 104 times and 433 times, respectively. Aberrations
      including only two chromosomes that seemed to be balanced were found only 19
      times. Losses resulting from structural abnormalities most frequently involved 5q
      (n = 100), 17p (n = 47), and 12p (n = 29), whereas gains of 11q (n = 21), 21q (n
      = 19), and 8q (n = 11) were observed. Using locus-specific probes, deletions of
      the EGR1 locus (5q31), of 7q31, and the TP53 gene were observed in 103 (82%), 57
      (46%), and 66 (53%) cases, respectively. In conclusion, in AML with a complex
      aberrant karyotype, loss of chromosomal material was observed much more often
      than gain. Unbalanced rearrangements leading to loss of chromosomal material are
      much more frequent than loss of whole chromosomes. These data suggest that in AML
      with a complex aberrant karyotype, loss of tumor-suppressor genes is a more
      important mechanism of leukemogenesis than activation of oncogenes, and that gene
      dosage effects may play a significant role in the pathogenesis of this AML
      subtype.

PMID- 12203787
TI  - Differential expression of multiple isoforms of the ELKS mRNAs involved in a
      papillary thyroid carcinoma.
AB  - A novel gene, ELKS, whose 5' portion was fused to the RET gene, was found in a
      papillary thyroid carcinoma. A cDNA of this gene obtained from a human-brain cDNA
      library revealed that it encoded a peptide of 948 amino acids, termed ELKSalpha.
      We identified four other isoforms, which encoded ELKSbeta, ELKSgamma, ELKSdelta,
      and ELKSepsilon proteins consisting, respectively, of 992, 720, 1088, and 1116
      amino acid residues. Analysis of the gene structure revealed that the isoforms
      were generated by alternative splicing. Isoforms beta, gamma, delta, and epsilon
      all contain an optional exon (exon14a), but ELKSgamma, -delta, and -epsilon lack
      exon 1b. ELKSgamma lacks exons 3 to 6. ELKSdelta and -epsilon lack exons 12 and
      17; ELKSepsilon contains an optional exon (exon 6a). Analysis by RT-PCR suggested
      that ELKSalpha and ELKSbeta mRNAs are abundant in the brain, ELKSdelta and
      ELKSepsilon mRNAs predominate in testis and thyroid, and ELKSepsilon mRNA
      predominates in other tissues. To prove whether the fusion of different ELKS
      isoforms to RET (between ELKS coiled-coil domains and the RET kinase domain)
      could produce chimeric proteins that could be autophosphorylated, we synthesized
      ELKSgamma-RET, ELKSdelta-RET, and ELKSepsilon-RET fusion proteins in vitro.
      Immunoblotting with anti-ELKS, anti-RET, and anti-phosphotyrosine antibodies
      demonstrated that the chimeric proteins were constitutively phosphorylated at
      tyrosine residues, whereas native RET protein was not. These results indicate
      that the ELKS gene is alternatively spliced, and that every type of ELKS-RET
      chimeric protein having oligomerization domains can activate RET's cytoplasmic
      tyrosine kinase.

PMID- 12203788
TI  - Hemizygous deletions in the HLA region account for loss of heterozygosity in the
      majority of diffuse large B-cell lymphomas of the testis and the central nervous
      system.
AB  - Loss of heterozygosity (LOH) is a major mechanism for inactivation of tumor
      suppressor genes and has been observed in various solid tumors and lymphomas. The
      human leukocyte antigen (HLA) region is located at chromosome band 6p21.3, and
      loss or alteration of this region may provide tumor cells with a mechanism to
      escape from the immune system. We previously identified small homozygous
      deletions within the HLA class II region in many of the diffuse large B-cell
      lymphomas (DLCLs) of the central nervous system (CNS) and the testis. In the
      present study, we focused on the mechanism leading to LOH in the HLA region.
      Twenty microsatellite markers, of which 12 were specific for HLA, were applied on
      11 extranodal DLCLs of the CNS and 28 of the testis. Additionally, fluorescence
      in situ hybridization with seven HLA-specific probes and a centromere 6-specific
      probe was performed on 20 cases to study the mechanism of LOH. In contrast to
      previously published data on spontaneously mutated lymphoblastoid cell lines,
      intrachromosomal hemizygous deletion, not mitotic recombination, was the major
      cause of LOH of the HLA region in these lymphomas. However, opposed to data in
      colorectal cancer, these deletions were rarely (one of nine cases) associated
      with an interchromosomal rearrangement such as a translocation.

PMID- 12203789
TI  - A 10-Mb paracentric inversion of chromosome arm 2p inactivates MSH2 and is
      responsible for hereditary nonpolyposis colorectal cancer in a North-American
      kindred.
AB  - Genomic deletions of the MSH2 gene are a frequent cause of hereditary
      nonpolyposis colorectal cancer (HNPCC), a common hereditary predisposition to the
      development of tumors in several organs including the gastrointestinal and
      urinary tracts and endometrium. The mutation spectrum at the MSH2 gene is
      extremely heterogeneous because it includes nonsense and missense point
      mutations, small insertions and deletions leading to frameshifts, and larger
      genomic deletions, the latter representing approximately 25% of the total
      mutation burden. Here, we report the identification and molecular
      characterization of the first paracentric inversion of the MSH2 locus known to
      cause HNPCC. Southern blot analysis and inverse PCR showed that the centromeric
      and telomeric breakpoints of the paracentric inversion map within intron 7 and to
      a contig 10 Mb 3' of MSH2, respectively. Pathogenicity of the paracentric
      inversion was demonstrated by conversion analysis. The patient's lymphocytes were
      employed to generate somatic cell hybrids to analyze the expression of the
      inverted MSH2 allele in an Msh2-deficient rodent cellular background. The
      inversion was shown to abolish MSH2 expression by both northern and western
      analysis. This study confirms that Southern blot analysis still represents a
      useful and informative tool to screen for and identify complex genomic
      rearrangements in HNPCC. Moreover, monoallelic expression analysis represents an
      attractive approach to demonstrate pathogenicity of unusual mutations in
      autosomal dominant hereditary conditions.

PMID- 12203790
TI  - Genomewide DNA hypomethylation is associated with alterations on chromosome 8 in
      prostate carcinoma.
AB  - To elucidate the relationship between genomewide DNA hypomethylation and
      chromosome instability, 55 prostate carcinoma specimens were analyzed for extent
      of hypomethylation by Southern blot analysis of LINE-1 sequence methylation and
      for loss or gain of chromosomal material by comparative genomic hybridization.
      Seventeen (31%) tumors showed strong hypomethylation of DNA, whereas four (7%)
      displayed slight hypomethylation and the rest of the tumors normal-level
      methylation. Chromosomal aberrations were observed in 34 carcinomas. The most
      frequent chromosomal alterations were loss of 13q in 18 cases and aberrations in
      8p (loss) or 8q (gain) in 16 cases. The presence of chromosomal loss or gain was
      significantly associated with the presence of strong hypomethylation. A striking
      correlation (P = 0.00001) was observed between aberrations on chromosome 8 and
      hypomethylation, whereas no association was seen between DNA hypomethylation and
      loss of 13q. The association between DNA hypomethylation and the presence of
      metastases was statistically significant (P = 0.044), and both chromosomal
      alterations and DNA hypomethylation tended to be more frequent in higher-stage
      tumors. In conclusion, the data indicate that hypomethylation is associated with
      chromosomal instability in prostate cancer. Specifically, a surprisingly strong
      association between alterations on chromosome 8 and genomewide hypomethylation
      was found. This association suggests that DNA hypomethylation and alterations in
      chromosome 8 may be mechanistically linked to each other in prostate carcinoma.

PMID- 12203791
TI  - Chromosomal aberrations in prostate cancer xenografts detected by comparative
      genomic hybridization.
AB  - A major problem in studying prostate cancer has been the lack of model systems
      because of the difficulties in growing prostate cancer cells in vitro. Recently,
      however, several human prostate cancer xenografts, grown in immune-deficient
      mice, have been established. Here, we characterized 13 such xenografts (LuCaP
      23.8, 23.12, 35, 41, 49, 58, 69, 70, 73, LAPC-4AD, LAPC-4AI, LAPC-9AD, and LAPC
      9AI) as well as one prostate cancer cell line (22Rv1) derived from a xenograft
      for chromosomal alterations by comparative genomic hybridization and a
      modification of multicolor fluorescence in situ hybridization. On average, the
      xenografts contained 13 (range 5-28) aberrations, 5 (1-13) gains, and 8 (1-15)
      losses, per case. The chromosome arms that most often contained losses were 2q,
      5q, 6q, 8p, 13q, and 18q, and gains were 7q, 8q, and Xq. The same regions were
      previously shown to be often altered in advanced prostate carcinomas in patients.
      The androgen-dependent and corresponding androgen-independent sublines of LAPC-4
      and LAPC-9 shared all genetic alterations, suggesting that the transition of the
      growth from androgen dependency to independence does not involve major
      chromosomal aberrations in these two models. In conclusion, the identified
      genetic aberrations lay the groundwork for further detailed genetic analyses of
      these xenografts.

PMID- 12203792
TI  - Silencing of the PTEN tumor-suppressor gene in anaplastic thyroid cancer.
AB  - Germline mutations in the tumor-suppressor gene PTEN (MMAC1, TEP1) are found in
      Cowden syndrome, which predisposes to hamartomas, breast cancer, trichilemmomas,
      and thyroid tumors of follicular epithelium. PTEN has also been found to be
      somatically deleted, mutated, and/or silenced in various sporadically occurring
      cancers such as glioblastoma, breast cancer, kidney cancer, malignant melanoma,
      and endometrial cancer. Loss or reduction of PTEN protein expression as well as
      inappropriate subcellular compartmentalization is seen in non-medullary thyroid
      cancers. However, although allelic loss of the PTEN locus in 10q23.3 is
      frequently seen, this is not coupled with mutations in the PTEN gene. To approach
      further the frequency and mechanism behind PTEN silencing, we screened a panel of
      87 sporadic thyroid tumors for PTEN mRNA expression, including 14 anaplastic
      carcinomas, 37 follicular carcinomas, 21 atypical adenomas, and 15 ordinary
      adenomas. Complete loss of PTEN mRNA expression was evident in six of the tumors,
      including four anaplastic carcinomas, one widely invasive carcinoma, and one
      ordinary adenoma. The transcriptional silencing of PTEN was significantly
      associated with the anaplastic subtype, suggesting that PTEN is involved in the
      carcinogenesis of highly malignant or late-stage thyroid cancers, whereas this
      particular mechanism appears to be of minor importance in differentiated
      follicular thyroid tumors. No association was observed between the expression,
      loss of heterozygosity, and mutation status in the 33 cases in which these
      parameters were compared. This indicates that PTEN silencing is a result of a
      wide variety of epigenetic and/or structural silencing mechanisms rather than a
      consequence of structural biallelic inactivation of the classical type.
      Furthermore, the high rate of alterations in the 10q23 region might indicate the
      presence of an as-yet unknown tumor-suppressor gene with an important role in the
      development of thyroid tumors.

PMID- 12203793
TI  - MEN1 tumor-suppressor protein localizes to telomeres during meiosis.
AB  - Multiple endocrine neoplasia type 1 is an autosomal dominant cancer
      predisposition syndrome caused by mutations in the tumor-suppressor gene MEN1.
      The gene encodes a nuclear protein, menin, with no recognized functional motifs.
      Menin has been shown negatively to regulate transcriptional activation mediated
      by JunD, although the significance of this interaction in normal cell physiology
      and how the absence of menin leads to tumorigenesis are unknown. Menin is highly
      expressed in testes. We used immunocytochemistry to explore its role in meiosis
      and found that it localizes exclusively at telomeres. JunD was not found at
      telomeres in meiotic cells. In view of elevated telomerase activity or abnormal
      telomere structure in virtually all malignancies, regulation of telomere function
      would be an appealing role for a tumor suppressor. However, menin does not
      specifically associate with telomeres in somatic cells, as indicated by lack of
      co-localization with the known telomeric protein TRF2. Cells overexpressing menin
      had normal telomerase activity, and tumors with homozygous MEN1 mutations showed
      no aberrations in telomere length, indicating that menin does not directly
      regulate telomerase activity. The role of menin at meiotic telomeres appears to
      be independent of JunD and may not have a counterpart in somatic cells. These
      results suggest that menin may play different roles in different tissues through
      interactions with different proteins.

PMID- 12203794
TI  - High sensitivity of detection of TP53 somatic mutations by fluorescence-assisted
      mismatch analysis.
AB  - We analyzed exons 5-9 of the TP53 gene in 41 breast cancers using direct
      sequencing, PCR-SSCP (single-strand conformation polymorphism), and fluorescence
      assisted mismatch analysis (FAMA), to test the level of specificity and
      sensitivity of each method. A major issue for the correct detection of TP53
      somatic mutations in primary tumors is often represented by the large amount of
      normal DNA, which can cause excessive dilution of the mutant allele, with
      consequent possible false-negative results. High sensitivity upon dilution of the
      mutant allele has been demonstrated for FAMA, a method based on the chemical
      cleavage of a mismatch within heteroduplex DNA molecules. Exons 5-9 of the TP53
      gene were analyzed by FAMA using only two long bifluorescent fragments.
      Differences in sensitivity, accuracy, and specificity were observed among the
      above-mentioned procedures. Thirteen of the 41 samples (31.7%) revealed TP53
      genetic alterations by automated sequencing, 19 samples (46.3%) were positive for
      SSCP, whereas 14 samples (34%) showed variants detectable by FAMA. Seven samples
      were positive in SSCP, but negative in both FAMA and sequencing assays; however,
      2 SSCP-negative samples revealed evident signals by FAMA, indicating the presence
      of TP53 mutations. One of the latter samples showed the alteration by sequence
      analysis, whereas the other failed to reveal the mutation signal even by
      sequencing, as a consequence of the very small amount of the mutant allele
      resulting from the excess of contaminating normal DNA. Our results show that FAMA
      may represent a suitable and accurate assay for the routine diagnosis of TP53
      somatic mutations in DNAs from solid tumor biopsies.

PMID- 12203795
TI  - LAF4, an AF4-related gene, is fused to MLL in infant acute lymphoblastic
      leukemia.
AB  - Infant acute lymphoblastic leukemia (ALL) with MLL gene rearrangements is
      characterized by a proB phenotype and a poor clinical outcome. We analyzed an
      infant proB ALL with t(2;11)(p15;p14) and an MLL rearrangement on Southern blot
      analysis. Rapid amplification of cDNA ends-polymerase chain reaction (PCR) and
      reverse transcriptase-PCR identified the LAF4 gene mapped on chromosome region
      2q11.2-q12 as a fusion partner of the MLL gene. The LAF4 gene was identified
      previously by its high sequence homology to the AF4 protein and encodes a protein
      of 1,227 amino acids. The t(4;11)(q21;q23), creating the MLL-AF4 chimeric
      transcripts, is the predominant 11q23 chromosome translocation in infant ALL and
      is associated with an extremely poor prognosis. Our findings further suggest that
      fusion of MLL to one of the AF4 family members (AF4/LAF4/AF5Q31) might determine
      a proB-cell phenotype in infant leukemia.

PMID- 12203796
TI  - Palatal adhesion: the treatment of unilateral palatal paralysis after high vagus
      nerve injury.
AB  - BACKGROUND: Resection of skull base tumors commonly necessitates intraoperative
      sacrifice of lower cranial nerves at the level of the jugular foramen. Sequelae
      of unilateral vagus nerve loss include ipsilateral laryngeal paralysis,
      ipsilateral palatal and pharyngeal paralysis, and velopharyngeal incompetence
      (VPI) marked by hypernasal speech and nasopharyngeal reflux of liquids during
      swallowing. METHODS: Palatal adhesion (PA), a procedure whereby the unilaterally
      paralyzed palate is attached to the posterior pharyngeal wall, decreases the size
      of the velopharyngeal port and minimizes the symptoms. This study assessed the
      outcome of PA in 31 patients with VPI secondary to proximal vagus nerve injury.
      RESULTS: PA decreased postoperative nasality in 96% of patients. Nasopharyngeal
      reflux was significantly improved in 83%. Three patients (11%) had minor wound
      breakdown postoperatively, all of which healed completely with conservative
      management. CONCLUSION: PA offers a favorable result with minimal concomitant
      morbidity and is recommended for patients with VPI secondary to unilateral
      proximal vagus nerve paralysis.

PMID- 12203797
TI  - Risk factors for late cervical lymph node metastases in patients with stage I or
      II carcinoma of the tongue.
AB  - BACKGROUND: Many histopathologic parameters in squamous cell carcinoma of the
      tongue have been identified as predictive factors for cervical lymph metastasis.
      However, predictive factors for occult cervical lymph node metastases and the
      criterion for elective therapy remain inconclusive. This study analyzed the
      clinicopathologic factors associated with late cervical lymph node metastases in
      patients with carcinoma of the tongue. METHODS: The clinicopathologic features of
      50 consecutive patients seen between January 1985-December 1996 with previously
      untreated stage I or II squamous cell carcinoma of the tongue were reviewed. All
      patients were treated with partial glossectomy without elective neck dissection.
      Their mean age was 54.5 y (range, 23-90 y) and the male-female ratio was 1.2:1
      (27 men and 23 women); 30 cases were stage I, and 20 cases were stage II.
      Clinicopathologic factors were analyzed to determine factors predicting late
      cervical lymph node metastasis. RESULTS: The overall cervical lymph node
      metastasis rate was 14.0% (7 of 50). Clinicopathologic factors significantly
      associated with the development of cervical lymph node metastasis were tumor size
      (> or =30 mm), tumor depth (> or =4 mm), differentiation, mode of invasion,
      microvascular invasion, and histologic grade of malignancy. In a multivariate
      logistic regression analysis, moderately differentiated squamous cell carcinoma
      of the tongue with tumor depth > or =4 mm had predictive value for late cervical
      lymph node metastasis and diminished overall survival (odds ratio, 10.0; p =.02;
      hazards ratio, 7.0; p =.039). CONCLUSIONS: The findings of this study demonstrate
      tumor depth > or =4 mm moderately differentiated squamous cell carcinoma of the
      tongue have a substantially higher rate of late cervical metastases. In the basis
      of these data, it is our recommendation that this be used in the decision to
      electively treat the neck.

PMID- 12203798
TI  - Patients with head and neck cancer cured by radiation therapy: a survey of the
      dry mouth syndrome in long-term survivors.
AB  - BACKGROUND: Xerostomia can have a significant impact on the quality of life of
      patients treated by radiation therapy (RT) for cancer in the head and neck. The
      first aim of the study was to evaluate the degree of xerostomia in 39 long-term
      survivors treated between 1965-1995 by conventional two-dimensional radiation
      therapy and currently without evidence of disease. The second aim was to develop
      a concise instrument to evaluate the subjective aspects of xerostomia. METHODS: A
      newly developed questionnaire and a visual analog scale (VAS) were used in
      analyzing the degree of dry mouth and xerostomia-related problems. The radiation
      dose received by the major salivary glands was estimated by analyzing two
      dimensional simulation films. RESULTS: Sixty-four percent of the patients
      experienced a moderate to severe degree of xerostomia. In the multivariate
      analysis, three questions regarding dry mouth, eating, and speech were
      particularly discriminatory for establishing the degree of xerostomia as
      expressed by the VAS score. CONCLUSIONS: In this survey, 64% of the long-term
      survivors, after treatment by conventional two-dimensional radiation therapy for
      a malignancy in the head and neck region, still experienced a moderate to severe
      degree of permanent xerostomia. A simplified instrument to evaluate xerostomia
      subjectively can consist of the VAS score and three graded questions.

PMID- 12203799
TI  - Stereotactic radiosurgery for locally recurrent nasopharyngeal carcinoma.
AB  - BACKGROUND: Stereotactic radiosurgery has been used to treat intracranial tumors.
      Recently, it has also been used for the treatment of head and neck tumors
      involving the base of skull, including recurrent NPC. METHODS: From October 1994
      to April 1999, 36 patients with recurrent NPC, were retreated by stereotactic
      radiosurgery. These patients received radiosurgery as a boost treatment after
      reirradiation for recurrence. The external RT dose ranged from 20 to 60 Gy. The
      tumor volume ranged from 3.58 to 24.6 cc. The target surface dose ranged from 8
      to 20 Gy. The median follow-up was 22.1 months. RESULTS: The 3-year local control
      rate was 56%. The 5-year overall survival was 49%. Persistence after radiosurgery
      had a worse survival than those who had secondary recurrence. Age and gender were
      marginally significant. No patient had new severe complications after
      retreatment. Four patients (11%) had nasopharyngeal necrosis after radiosurgery,
      none had nasal bleeding or headache, but a foul odor was present in one patient.
      CONCLUSIONS: Conformal radiotherapy and stereotactic radiotherapy provide good
      local control and survival without severe complications for patients with
      recurrent NPC.

PMID- 12203800
TI  - Radiofrequency ablation of head and neck tumors: dramatic results from
      application of a new technology.
AB  - BACKGROUND: Radiofrequency ablation (RFA) is a new treatment modality used over
      the past decade predominantly in the treatment of unresectable liver tumors. We
      find no prior reported series on the use of RFA for malignant tumors of the head
      and neck. METHODS: Four patients with recurrent tongue tumors not amenable to
      standard surgical or radiation therapy were treated with RFA administered
      transorally, endoscopically, or percutaneously. RESULTS: There was no
      perioperative mortality. Significant palliation was achieved consisting of
      substantial reduction in tumor size and alleviation of tumor-induced pain. One
      patient has survived for 8 months with no progression of tumor. Three patients
      had complications, including line sepsis, pneumonia, and enlargement of an
      orocutaneous fistula. CONCLUSIONS: RFA was relatively straightforward to apply,
      achieved substantial palliation, and was associated with minimal perioperative
      morbidity and no mortality. It might easily be combined with other therapies such
      as chemotherapy, immunotherapy, or radiation. Further investigation is necessary
      and ongoing.

PMID- 12203801
TI  - Supracricoid partial laryngectomy as salvage surgery after radiation failure.
AB  - BACKGROUND: Radiotherapy is often chosen as the definitive treatment for early
      stage laryngeal carcinoma. Total laryngectomy is the main procedure for failures.
      Endoscopic treatment of recurrences by CO(2) laser has found limited application.
      Partial laryngectomy through an external approach has been proposed as salvage
      surgery, and the vertical partial laryngectomy (VPL) is the most mentioned
      surgical technique in the literature, although there are, to date, very few
      reports regarding the use of the supracricoid partial laryngectomy (SCPL) as
      salvage surgery after radiation failure. OBJECTIVES: The aim of the study is to
      check the feasibility of SCPL with cricohyoidoepiglottopexy (CHEP) or
      cricohyoidopexy (CHP) in patients with laryngeal recurrence after radiation
      failure and to evaluate the oncologic results, morbidity, and functional outcome.
      METHODS: Fifteen consecutive patients were treated with salvage intent by SCPL
      from January 1992 to December 1998. CHEP and CHP were performed in 11 and 4
      patients, respectively. Five patients underwent homolateral surgical neck
      dissection, and one underwent bilateral neck dissection. All patients had a
      temporary tracheostomy, and two patients required percutaneous endoscopic
      gastrostomy (PEG) to ensure feeding. Functional rehabilitation started 2 weeks
      after the operation. RESULTS: The results have been evaluated in terms of
      oncologic outcome and functional preservation. Twelve patients are alive with a
      minimum follow-up of 36 months and 3 patients died after 36 days, 6 and 14 months
      after surgery, the first and second patient from heart failure and the third from
      lung metastasis. Respiratory function was recovered in all cases. Oral intake
      began 12 days after surgery, and in 14 cases satisfactory swallowing was
      recovered 30 days after surgery. An acceptable quality of the voice was achieved
      by most patients, and a high rate of local immediate complications was solved in
      all cases. CONCLUSIONS: SCPL represents an effective technique as salvage
      treatment of laryngeal cancer after exclusive radiotherapy; there is a good
      functional recovery with acceptable morbidity and good oncologic long-term
      control.

PMID- 12203802
TI  - An ex vivo study exploring the diagnostic potential of 1H magnetic resonance
      spectroscopy in squamous cell carcinoma of the head and neck region.
AB  - BACKGROUND: Definitive diagnosis of head and neck cancer is generally made by
      histopathologic evaluation. Management and prognosis largely depend on accurate
      and timely diagnosis. We have explored the use of (1)H magnetic resonance
      spectroscopy in search of a better or complementary diagnostic technique.
      METHODS: Tumor and adjacent normal tissue specimens (n = 135) from untreated head
      and neck cancer patients (n = 40) were obtained and subjected to spectroscopic
      evaluation followed by histopathologic analysis. Data were partitioned into
      training and test sets and subjected to multivariate analysis. RESULTS: The
      resonances from taurine, choline, glutamic acid, lactic acid, and lipid were
      found to have diagnostic potential by our optimal region selection algorithm.
      Multivariate analysis of the spectral data differentiated between normal and
      malignant tissues, with an overall accuracy of 92.6% (training set, 97.3%; test
      set, 87.3%), an overall sensitivity of 93% (test set, 90%), and an overall
      specificity of 92% (test set, 82.6%). CONCLUSIONS: (1)H magnetic resonance
      spectroscopy combined with multivariate methods of analysis can distinguish
      between normal and malignant squamous cell tissue, and this may lead to the
      development of an objective and noninvasive diagnostic procedure.

PMID- 12203803
TI  - Soluble Tie-2 receptor levels independently predict locoregional recurrence in
      head and neck squamous cell carcinoma.
AB  - BACKGROUND: This study assessed two circulating angiogenic receptors as tumor
      markers in patients with head and neck squamous cell carcinoma (HNSCC): soluble
      vascular endothelial factor growth receptor-1 (sVEGFR1) and soluble Tie-2
      receptor (sTie2R). METHODS: Sera from 79 newly presenting patients with HNSCC and
      from 22 controls were assayed using sandwich ELISA. Median follow-up was 35
      months after curative treatment. Analysis was carried out to compare levels
      between HNSCC patients and controls and to ascertain relationships with
      clinicopathologic and outcome variables. RESULTS: Soluble VEGFR1 was not elevated
      in the HNSCC group and was not related to any of the clinicopathologic or outcome
      variables. Soluble Tie2R was also not elevated in HNSCC patients or related to
      the clinicopathologic variables but was associated with locoregional recurrence
      (p =.009). Raised sTie2R (>64 ng/mL) independently predicted recurrence (p =.007)
      with a relative risk of 3.0 (95% CI, 1.7-5.0). CONCLUSIONS: Soluble Tie2R is an
      independent predictor of locoregional recurrence in HNSCC.

PMID- 12203804
TI  - Distant metastases of adenoid cystic carcinoma of the salivary glands and the
      value of diagnostic examinations during follow-up.
AB  - BACKGROUND: Adenoid cystic carcinoma (ACC) accounts for approximately 10% of all
      neoplasms of the salivary glands. Late distant metastases and local recurrences
      are responsible for a rather low long-term survival rate. AIM: To study the
      metastasizing pattern of ACC of the salivary glands in 51 patients. METHOD: Fifty
      one patients with an ACC in the intraoral/sublingual salivary glands (n = 30),
      parotid gland (n = 8), submandibular gland (n = 2), maxillary sinus (n = 6), and
      nasal cavity (n = 5) have been studied. The male-female ratio was 1:1, the mean
      age was 54.3 (range, 19-81) years. In 30 cases treatment consisted of surgery and
      radiotherapy. In 13 cases surgery alone was carried out. The average follow-up
      time was 117.8 (range, 1-171) months. RESULTS: In 28 cases (54.9%) distant
      metastases occurred, and in 3 patients (5.8%) regional lymph node metastases
      occurred. In 12 of the 28 patients with distant metastases (42.8%), only the
      lungs were involved, whereas in 5 of the 28 patients (17.8%), the distant
      metastases occurred in other organs (eg, bones and brain). In 11 of the 28
      patients (39.2%) metastases were found both in the lungs and other organs. Twenty
      four of the 51 patients (47.0%) died because of their tumor. The average time
      between the occurrence of lung metastases and death was 32.3 months and between
      the occurrence of metastases elsewhere and death 20.6 months. CONCLUSION: Distant
      metastases of ACC of the salivary glands occur most often in the lungs. Although
      these lung metastases are the first to occur, these patients die later than
      patients with distant metastases in other organs. The value of annual chest films
      or other tests for the presence of distant metastases during follow-up after
      surgical removal of an ACC seems rather questionable.

PMID- 12203805
TI  - Nuclear and cytoplasmic p53 expression in pharyngeal squamous cell carcinoma:
      prognostic implications.
AB  - BACKGROUND: The role of p53 expression in human neoplasms is still controversial,
      and it has been associated with both favorable and unfavorable outcome of the
      patients. Also cytoplasmic expression of p53 protein has been reported to affect
      survival in some cancers. Furthermore, an association between p53 and beta
      catenin expression has been demonstrated. We studied the expression of p53 in a
      large group of oropharyngeal and hypopharyngeal squamous cell carcinomas and its
      relation to catenin expression, histologic differentiation, clinical data, and
      prognosis. METHODS: Primary tumors for analyses were obtained from 123 patients
      diagnosed with squamous cell carcinoma of the oropharynx or hypopharynx between
      1975 and 1998 in Eastern Finland. Immunohistochemistry was used to evaluate the
      expression of p53 as well as alpha-, beta-, and gamma-catenins. RESULTS: In the
      primary tumors (n = 123), the nuclear p53 expression index was low in 42 (34%),
      intermediate in 38 (31%), and high in 43 (35%) cases. Cytoplasmic p53 expression
      was present in 56 (46%) and absent in 67 (54%) tumors. In univariate analyses
      (Kaplan-Meier), hypopharyngeal primary site (p =.02), high T class (p <.0005),
      presence of distant metastases (p =.02), low Karnofsky performance index (p
      <.0005), high nuclear p53 expression index (p =.01), and positive cytoplasmic p53
      expression (p =.04) predicted poorer overall survival (OS). In Cox proportional
      hazards model, only T class (p =.0005), Karnofsky performance index (p =.005),
      and nuclear beta-catenin expression (p =.038) predicted poorer OS. CONCLUSION:
      Positive cytoplasmic p53 expression and nuclear p53 overexpression seem to relate
      to more aggressive features and unfavorable outcome in pharyngeal squamous cell
      carcinoma (PSCC). However, unlike more traditional variables, p53 expression is
      not an independent predictor of disease outcome in PSCC.

PMID- 12203806
TI  - Cyclooxygenase-2: a novel molecular target for the prevention and treatment of
      head and neck cancer.
AB  - Cyclooxygenase-2 (COX-2), an enzyme that catalyzes the synthesis of
      prostaglandins, is overexpressed in a variety of premalignant and malignant
      conditions, including oral leukoplakia and squamous cell carcinoma of the head
      and neck. Increased levels of COX-2 may contribute to carcinogenesis by
      modulating xenobiotic metabolism, apoptosis, immune surveillance, and
      angiogenesis. In experimental models, newly developed selective COX-2 inhibitors
      suppress the formation of tumors, including tongue cancer. These findings
      provided a rationale for a number of chemoprevention trials that are underway.
      Selective COX-2 inhibitors also suppress the growth and metastases of established
      tumors and enhance the anticancer activity of both radiotherapy and chemotherapy
      in experimental animals. In this review, evidence is presented that inhibition of
      COX-2 represents a promising strategy to prevent or possibly treat human head and
      neck cancers.

PMID- 12203807
TI  - The sarcomatous guise of cervical ectopic hamartomatous thymoma.
AB  - BACKGROUND: Ectopic hamartomatous thymoma is a rare benign neoplasm occurring in
      the deep soft tissues adjacent to the sternoclavicular joint. Although clinical
      presentation and diagnostic imaging can be consistent with a malignant lesion
      such as a sarcoma, recognition of pathologic features can readily exclude such a
      diagnosis. However, this remains a challenge caused by their unusual histologic
      features and diverse composition. Recognition of this tumor is, however,
      important, because it follows a benign clinical course, and conservative surgical
      excision is the therapy of choice. METHODS: A literature review of all reports of
      ectopic hamartomatous thymoma was undertaken and compared with our indexed case.
      RESULTS: From this review, we identified 26 previous reports. Most patients were
      men, with a 4.5:1 predominance. There was a wide range of ages at presentation,
      from 26 to 79 years. All tumors were located in the lower neck, with the
      exception of one arising presternally. Treatment predominantly consisted of tumor
      resection, with no reported recurrences on follow-up. CONCLUSIONS: We conclude
      that ectopic hamartomatous thymoma is an extremely rare neoplasm usually
      presenting in the lower neck. Correct identification of this tumor is important,
      because it follows a benign course, and surgical excision is adequate therapy.

PMID- 12203808
TI  - Angiofibroma of the larynx: report of a case with clinical and pathologic
      literature review.
AB  - BACKGROUND: Angiofibromas are uncommon vascular tumors with a strong predilection
      for the nasopharynx of adolescent males. Although they are slow growing and
      histologically benign, they have the potential to cause significant morbidity
      with laryngeal involvement. METHODS: We describe the clinical characteristics,
      histopathologic findings, differential diagnosis, preoperative evaluation, and
      management of a case of laryngeal angiofibroma. RESULTS: The patient was
      initially seen with a 2 1/2-year history of progressive dyspnea and dysphagia.
      Preoperative evaluation suggested a vascular mass involving the left supraglottic
      larynx. A partial laryngopharyngectomy was performed without complication. The
      patient is alive and disease free 3 years postoperatively. Final histopathologic
      diagnosis is consistent with angiofibroma. CONCLUSIONS: Laryngeal angiofibroma is
      an extremely rare entity. Adequate preoperative imaging is necessary to confirm
      the vascularity of this lesion, because ill-planned biopsy may lead to
      significant blood loss. The role of preoperative embolization of other laryngeal
      vascular lesions has been well documented and may be useful in the management of
      laryngeal angiofibroma.

PMID- 12203809
TI  - Somatostatin analog treatment of a cervical thoracic duct fistula.
AB  - BACKGROUND: Reoperation for recurrent thyroid cancer poses an increased risk of
      complications, including thoracic duct fistula. Treatment of this complication is
      controversial. A survey of thoracic literature reports the use of somatostatin
      analog, whereas no cases have reported the use of this therapy in cases arising
      from neck dissection. METHODS: We report a 16-year-old girl with recurrent
      papillary thyroid cancer who had a persistent lymphatic-cutaneous fistula develop
      after repeat modified left neck dissection. Despite conservative management,
      drainage persisted for 2 months. A regimen was begun that included TPN and
      injections of a somatostatin analog. RESULTS: Treatment with a somatostatin
      analog resulted in an immediate attenuation of drainage and subsequent closure of
      the fistula after 16 days of treatment. CONCLUSION: The use of somatostatin
      analog can increase the success of conservative management of thoracic duct
      fistulae.

PMID- 12203810
TI  - Energetics and evolution: an emerging research domain.
AB  - The study of energetics is important to human biology because the availability
      and utilization of food energy influence health, survival, and reproduction. Over
      the last decade, human biologists, biological anthropologists, and other
      evolutionary scientists have increasingly come to recognize the importance of
      energy dynamics in shaping evolutionary processes. Thus far, different lines of
      energetics research have been conducted largely in isolation from one another.
      This thematic collection examines topics of evolutionary energetics from several
      different perspectives, drawing together research from human paleontology,
      comparative primate and mammalian biology, human population biology, and
      mathematical modeling. It represents a starting point for further integrative
      research on human evolutionary energetics.

PMID- 12203811
TI  - Energetic consequences of being a Homo erectus female.
AB  - Body size is one of the most important characteristics of any animal because it
      affects a range of behavioral, ecological, and physiological traits including
      energy requirements, choice of food, reproductive strategies, predation risk,
      range size, and locomotor style. This article focuses on the implications of
      being large bodied for Homo erectus females, estimated to have been over 50%
      heavier than average australopithecine females. The energy requirements of these
      hominins are modeled using data on activity patterns, body mass, and life history
      from living primates. Particular attention is given to the inferred energetic
      costs of reproduction for Homo erectus females based on chimpanzee and human
      reproductive scheduling. Daily energy requirements during gestation and lactation
      would have been significantly higher for Homo erectus females, as would total
      energetic cost per offspring if the australopithecines and Homo erectus had
      similar reproductive schedules (gestation and lactation lengths and interbirth
      intervals). Shortening the interbirth interval could considerably reduce the
      costs per offspring to Homo erectus and have the added advantage of increasing
      reproductive output. The mother would, however, incur additional daily costs of
      caring for the dependent offspring. If Homo erectus females adopted this
      reproductive strategy, it would necessarily imply a revolution in the way in
      which females obtained and utilized energy to support their increased energetic
      requirements. This transformation is likely to have occurred on several levels
      involving cooperative economic division of labor, locomotor energetics,
      menopause, organ size, and other physiological mechanisms for reducing the
      energetic load on females.

PMID- 12203812
TI  - Neandertal cold adaptation: physiological and energetic factors.
AB  - European Neandertals employed a complex set of physiological cold defenses,
      homologous to those seen in contemporary humans and nonhuman primates. While
      Neandertal morphological patterns, such as foreshortened extremities and low
      relative surface-area, may have explained some of the variance in cold
      resistance, it is suggested the adaptive package was strongly dependent on a rich
      array of physiological defenses. A summary of the environmental cold conditions
      in which the Neandertals lived is presented, and a comparative ethnographic model
      from Tierra del Fuego is used. Muscle and subcutaneous fat are excellent
      "passive" insulators. Neandertals were quite muscular, but it is unlikely that
      they could maintain enough superficial body fat to offer much cold protection. A
      major, high-energy metabolic adaptation facilitated by modest amounts of highly
      thermogenic brown adipose tissue (BAT) is proposed. In addition, Neandertals
      would have been protected by general mammalian cold defenses based on systemic
      vasoconstriction and intensified by acclimatization, aerobic fitness, and
      localized cold--induced vasodilation. However, these defenses are energetically
      expensive. Based on contemporary data from circumpolar peoples, it is estimated
      that Neandertals required 3,360 to 4,480 kcal per day to support strenuous winter
      foraging and cold resistance costs. Several specific genetic cold adaptations are
      also proposed--heat shock protein (actually, stress shock protein), an ACP*1
      locus somatic growth factor, and a specialized calcium metabolism not as yet
      understood.

PMID- 12203813
TI  - Comparative and evolutionary dimensions of the energetics of human pregnancy and
      lactation.
AB  - The purpose of this article is to compare the energetics of reproduction for
      human and other primates in order to evaluate the extent to which human
      reproductive energetics are distinct from other primates and other large-bodied
      placental mammals. The article also evaluates the energetics of human and primate
      gestation and lactation using data from a variety of different populations living
      under different environmental circumstances. Energetics refers to energy intake
      and expenditure, and changes in body fat stores. Human and nonhuman primates have
      longer periods of gestation and lactation and slower prenatal and postnatal
      growth than other mammals of similar size. This reduces daily maternal energy
      costs. The development of sizable fat stores is not unique to humans, but fat
      stores are typically greater in human females and may play a greater role in
      reproduction. The strategies used to meet the energy costs of pregnancy vary
      among populations of humans and nonhuman primates and among humans
      interindividual variability is high. In pregnancy, some increase energy intake
      but others apparently do not. Increases in metabolic efficiency are evident in
      some human populations, whereas decreases in physical activity occur, but are not
      seen in all human or primate populations. Lactation is more energetically costly
      on a daily basis among humans and nonhuman primates, but has not been as well
      studied. It appears that both nonhuman and human primates tend to increase energy
      intake to meet in part the cost of lactation. They also use other strategies such
      as relying on body tissue stores, reductions in physical activity, and/or
      increases in metabolic efficiency to meet the remainder of the cost. It is also
      clear that human females in different populations and different women in the same
      population use a different combination of strategies to meet the cost of
      lactation.

PMID- 12203814
TI  - Comparative energetics of primate fetal growth.
AB  - Among the primates, Homo sapiens has evolved a life history which includes long
      gestation, relatively slow growth to reproductive maturity, and large body size.
      While the slow growth rate may be linked to the energetic demands of having a
      large brain, there are other important morphological and physiological linkages
      that may be adaptive, including the development of significant fat stores with
      which to buffer against episodic and periodic energetic stress. In this
      comparative analysis of the energetic burden of pregnancy among primates
      (including humans), the daily energy investment in the development of neonatal
      tissue is modeled. During pregnancy, larger primates, notably the Hominidae,
      invest a smaller proportion of their maternal daily nonmaintenance energy budget
      in fetal tissue with increasing energy budget, allowing diverse adaptations,
      including foraging strategies which include folivory and mixed patterns of food
      getting, and meat consumption. Humans have a similar proportion of maternal daily
      nonmaintenance energy budget invested in fetal tissue with increasing energy
      budget to other apes and have a diet which is of much higher quality than
      predicted for body size and metabolic needs. The combination of high diet quality
      and low proportion of maternal daily nonmaintenance energy budget invested in
      fetal tissue allows greater brain size relative to body weight at birth compared
      with all other primates, apart from chimpanzees, and higher birthweight and body
      fatness at birth for a given body size than other primate species.

PMID- 12203815
TI  - Climatic influences on basal metabolic rates among circumpolar populations.
AB  - This article examines evidence for elevations in basal metabolic rate (BMR) among
      indigenous Northern (circumpolar) populations and considers potential mechanisms
      and the adaptive basis for such elevations. Data on BMR among indigenous (n = 109
      males; 122 females) and nonindigenous (n = 15 males; 22 females) circumpolar
      groups of North America and Siberia are compiled and compared to predicted BMRs
      based on three different references: body surface area (Consolazio et al., 1963),
      body mass (Schofield, 1985), and fat-free mass (Poehlman and Toth, 1995).
      Regardless of which reference is used, indigenous circumpolar groups show
      systematic and statistically significant elevations in BMR ranging from +7% to
      +19% above predicted values for indigenous men and from +3 to +17% for indigenous
      women. Nonindigenous males also show elevations in BMR, although not to the same
      extent as in indigenous men (deviations = +3 to +14%), whereas nonindigenous
      females show no clear evidence of elevated BMRs (deviations = -7 to +5%). This
      pattern of variation between indigenous and nonindigenous groups suggests that
      both functional and genetic factors play a role in metabolic adaptation to
      northern climes. Recent studies on the ecology and genetics of thyroid function
      offer insights into the mechanisms through which indigenous circumpolar
      populations may regulate metabolic rates. Studies of seasonal variation in
      thyroid hormone levels suggest that indigenous circumpolar populations may have a
      greater capacity to elevate BMR during severe cold than nonindigenous groups.
      Recent twin studies indicate a significant genetic component of thyroid responses
      to environmental stressors. Further research exploring the genetics of seasonal
      variation in thyroid function and BMR among circumpolar groups would advance
      understanding of the role that selection may have played in shaping metabolic
      variation.

PMID- 12203816
TI  - Somatic versus reproductive energy allocation in Papua New Guinea: life history
      theory and public health policy.
AB  - A fundamental evolutionary problem faced by organisms is how to allocate energy
      to somatic and reproductive functions in ways that optimize fitness. Given that
      energy is limited in all environments, energy allocation necessarily involves
      physiological tradeoffs between such factors as growth and reproduction,
      reproduction and condition, and current reproduction and future survival.
      Ultimately, the "decisions" that are made about energy allocation among growth,
      survival, and reproduction determine life history patterns and trajectories of
      organisms. For humans, knowing how energy allocation to reproduction will likely
      impact other aspects of the somatic well-being of individuals may also have
      practical implications for public health policy. This article reviews the
      evidence for energy tradeoffs between somatic and reproductive functioning in a
      range of human societies. It also seeks to corroborate the results of earlier
      work in Papua New Guinea on lactation-related maternal energy depletion using an
      independent measure of maternal energy reserves, tetrapolar bioelectrical
      impedance analysis. The current analysis shows that maternal energy reserves
      decline over the course of lactation and that a cumulative parity-specific
      decline in maternal energy reserves also exists. A longitudinal follow-up of five
      women over 11 years shows the decline to amount to about 3 mm of subcutaneous fat
      per round of pregnancy and lactation. The results corroborate predictions from
      life history theory and have applied public health implications. In particular,
      It is suggested that policies such as lactation advocacy that encourage enhanced
      energy allocation to reproduction in order to promote child health may have the
      unintended result of compromising maternal well-being, particularly in nations of
      the developing world. Consequently, it is recommended that nutritional support of
      mothers be implemented in concert with lactation promotion.

PMID- 12203817
TI  - Sexual division of labor: energetic and evolutionary scenarios.
AB  - This article examines comparative energetic data on hunter-gatherers in the
      context of evolutionary scenarios of the sexual division of labor, with respect
      to both specific task allocation and overall levels of daily physical activity.
      The division of labor between men and women, well marked in contemporary foraging
      societies, was once posited as the "true watershed" for the evolution of the
      genus Homo. Some research on brain-wiring even links sex differences in cognitive
      and spatial abilities to sex-specific foraging activities. Most recent
      evolutionary arguments posit that men focus on hunting and women on gathering
      activities to realize potentially conflicting mating and parenting goals. A range
      of cooperative strategies (male/female and female/female) for child provisioning
      is also under investigation. Attention to energetic and reproductive trade-offs
      has usefully challenged the proposition that women are excluded from big-game
      hunting due to constraints of foraging ecology and reproduction. Simplistic
      assumptions about gender roles are thus increasingly questioned in anthropology,
      as well as in archaeology. Current models in behavioral ecology explore ways in
      which foraging practices vary with ecological circumstances, aiming to derive
      testable hypotheses from fine-grained data on the behavior of contemporary hunter
      gatherers. Data on overall physical activity levels (PAL) can also serve to
      evaluate relative male/female workloads in modern groups, reconstruct hominid
      energy requirements and activity profiles, and examine changes with subsistence
      intensification. Male/female PAL ratios show that a task-specific division of
      labor does not readily extrapolate to 24-hour energy expenditure and that
      male/female differences in workloads were not necessarily reduced with the
      transition to agriculture. With respect to gender roles and PAL, a shift away
      from facile stereotypes of human behavior is evident. The challenge is to
      incorporate a range of behavioral responses to ecological circumstances in
      reconstructions of our evolutionary past.

PMID- 12203818
TI  - Energetics and optimization of human walking and running: the 2000 Raymond Pearl
      memorial lecture.
AB  - Humans seem to adjust their walking and running gaits to minimise the metabolic
      energy cost of locomotion. The walking speed that we tend to prefer is the one
      that minimises energy cost per unit distance, though faster speeds might seem
      preferable when time is valuable. At speeds up to 2 m/s, walking requires less
      energy than running, and we walk. At higher speeds, running is more economical,
      and we run. At each speed we use the stride length that minimises energy costs. A
      computer model that predicts metabolic rates for all conceivable gaits of a
      simple biped helps to understand these and other features of human gait. The
      energy cost of walking is increased on uphill slopes and also on soft ground.
      Consequently, zigzag paths should be preferred to straight ones, up hills of more
      than a critical gradient. Also, it may be more economical to divert a path around
      a hill than to travel along a straight line. Simple theories of optimum
      diversions are presented, both for hilly ground and for ground interrupted by
      marshy patches, on which costs of walking are increased. Energy costs are also
      increased by heavy loads, though it seems possible in some circumstances to carry
      moderate loads without measurable extra cost.

PMID- 12203819
TI  - Factor analysis of ethnic variation in the multiple metabolic (insulin
      resistance) syndrome in three Canadian populations.
AB  - This study describes and compares the pattern of risk factor clustering in
      multiple metabolic (insulin resistance) syndrome (MMS) in three Canadian ethnic
      groups (Indians, Inuit, non-Aboriginal Canadians). Three cross-sectional,
      population-based sample surveys in three contiguous regions of Canada were
      conducted during the late 1980s and early 1990s (Ontario, Manitoba, Northwest
      Territories). The combined dataset consists of 873 Cree-Ojibwa Indians from
      northern Ontario and Manitoba, 387 Inuit from the Northwest Territories, and
      2,670 non-Aboriginal Canadians (predominantly of European origin) in the province
      of Manitoba. The samples are representative of the noninstitutionalized, adult
      population of their respective catchment areas. Factor analysis transformed 10
      anthropometric and metabolic variables into three uncorrelated factors. Three
      factors, which together account for 64.3% of the variance, can be identified: an
      "obesity factor" (factor loadings for weight, height, waist and hip girth, and
      HDL-cholesterol); a "blood pressure factor" (factor loadings for mean systolic
      and diastolic BP and total cholesterol); and a "lipid/glucose factor" (factor
      loadings for triglycerides, total cholesterol, HDL, and fasting plasma glucose).
      Fasting insulin is available for only a subset of the data and separate analysis
      shows that it groups with glucose. Factor scores generated by the factor analysis
      differ according to ethnic group, diabetes status, and sex on multivariate
      analysis of variance. Indians have the highest scores for all three factors.
      Inuit have the lowest obesity scores and are not significantly different from non
      Aboriginal people with regard to the other two factors. MMS is prevalent in
      diverse ethnic groups but varies in the pattern of phenotypic expression, with
      some components more prominent in some groups.

PMID- 12203820
TI  - Nutritional status of children from Papua New Guinea: associations with
      socioeconomic factors.
AB  - Growth faltering has been well documented in children from Papua New Guinea,
      although there is evidence that broad processes of modernization, such as cash
      cropping, have resulted in increased body size. It is not clear, however, what
      household socioeconomic factors may be associated with larger body size in
      populations undergoing early stages of modernization. This cross-sectional study
      examined the nutritional status of children between birth and 5 years of age
      living near Kanabea, Papua New Guinea, a relatively remote outpost in the
      highland fringe experiencing a limited cash economy. Weight and height were
      measured on 260 children from 190 households. The mean z-scores of -2.26 +/- 1.50
      (SD) for height-for-age, -2.43 +/- 1.25 for weight-for-age, and -1.34 +/- 1.49
      for weight-for-height are suggestive of both acute and chronic malnutrition.
      Using a cut-off value of < or = -2SD, 68.8% of the children were stunted and/or
      wasted. These values are similar to those from a 1992-93 survey in the district,
      revealing that malnutrition remains a problem in the area. In this largely
      traditional horticultural group, educated mothers and mothers who spoke pidgin
      and/or English in addition to the local language had children with better z
      scores.

PMID- 12203821
TI  - Secular trend in the development of fatness during childhood and adolescence.
AB  - This study examined the development of fatness, as indexed by skinfold thickness,
      in healthy Caucasian children and adolescents residing in the same location in
      Canada in the 1960s and the 1990s. The data comes from two longitudinal studies,
      conducted approximately 30 years apart, of children aged 8-16 years. The first
      study (1964-1973) annually measured 207 males and 140 females. The second
      investigation (1991-1997) repeatedly measured 113 males and 115 females.
      Identical measurement tools and protocols were used for height, body mass, and
      skinfolds. Maturational age was estimated as a measure in years from age of peak
      height velocity. Males from the second investigation matured significantly (P <
      0.05) earlier. Multilevel regression modeling was utilized to determine
      developmental curves for the individuals within the two populations. When
      differences in height, body mass, and maturity were controlled, skinfold
      thicknesses of the males and females in the second study were significantly
      greater (P < 0.05) than age- and sex-matched peers in the first study. This was
      not seen in models of the BMI. The results suggest that when maturity and size
      were controlled, the fatness of children and adolescents increased over 30 years.

PMID- 12203822
TI  - Changing family structure in a modernizing society: a study of marriage patterns
      in a single Muslim village in Israel.
AB  - Among 1,875 couples from one Muslim village, 374 (20%) marriages were between
      first cousins. Among women born after 1920, the highest rates of first-cousin
      marriages were observed among those born between 1940-1959 (26%) and this pattern
      declined in the last two decades. The majority of first-cousin marriages were
      between offspring of brothers. Analyzed by 20-year periods, the pattern of first
      cousin marriages changed as the proportion of marriages between brothers'
      children decreased from 75% to 44%. Over the study period, more than 70% of
      marriages were between individuals born in the village and related to some
      degree. Examination of the marriages in which both spouses were born in the
      village demonstrated a preference to marry within the extended family; 68% of the
      women married a man with the same family name. Since the creation of the Israeli
      State, there have been significant changes among Israeli-Arab citizens. However,
      these data demonstrate that the tradition of marrying a relative remains central,
      although some changes in marriage preference have occurred.

PMID- 12203824
TI  - Two messenger RNA isoforms of the gonadotrophin-releasing hormone receptor,
      generated by alternative splicing and/or promoter usage, are differentially
      expressed in rainbow trout gonads during gametogenesis.
AB  - The recent cloning of a gonadotrophin-releasing hormone receptor (GnRH-R) cDNA
      from rainbow trout showed that it contains several in-frame ATG codons, one of
      which, ATG2, corresponds to that found in other species. However, an upstream
      codon, ATG1, could give rise to a protein with a larger extracellular domain.
      Using S1 nuclease assay and a method combining primer extension and RACE-PCR, we
      characterized a second population of mRNA, termed mRNA-2, with a distinct
      5'untranslated region and lacking ATG1. The genomic origin of the two mRNAs was
      determined by establishing the complete gene structure, which shows, for the
      first time in a vertebrate species that an alternative splicing and promoter
      usage generate two GnRH-R mRNA variants whose 5' extremities are encoded by two
      different exons. The analysis of the tissue distribution indicated that mRNA-2
      presents a broader pattern of expression and is detected at higher levels than
      mRNA-1. Interestingly, it was found that those two mRNAs are differentially
      expressed in male and female gonads during gametogenesis. In particular, the
      variations of mRNA-1 levels parallel those of sGnRH expression during
      spermatogenesis, indicating that tissue-specific processing of the GnRH-R mRNA
      may underlie the effects of GnRH as a paracrine/autocrine regulator of gonadal
      functions.

PMID- 12203823
TI  - Expression of leukemia inhibitory factor receptor and gp130 in mouse uterus
      during early pregnancy.
AB  - Leukemia inhibitory factor (LIF) is essential for implantation of mouse embryos.
      The aim of this study was to assess the expression and regulation of LIF receptor
      (LIFR) and gp130 mRNA in mouse uterus during early pregnancy using in situ
      hybridization and reverse transcription-polymerase chain reaction (RT-PCR). A
      strong level of LIFR mRNA signal was detected in the luminal epithelium on day 5
      of pregnancy. On day 6-8 of pregnancy, LIFR signal was mainly localized in the
      decidua. LIFR signal in the luminal epithelium of ovariectomized mouse was
      slightly stimulated by a combination of progesterone and estrogen. By RT-PCR,
      LIFR mRNA signal was detected in all of the uteri from day 1-8 of pregnancy,
      being at the highest level on day 5. A low level of gp130 mRNA signal was seen in
      the glandular epithelium on day 3 of pregnancy and reached a high level on day 4
      of pregnancy. gp130 signal in the decidua appeared on day 6 of pregnancy and
      reached a high level on day 7 and 8 of pregnancy. After the ovariectomized mouse
      was treated with a combination of progesterone and estrogen, a strong gp130
      signal was observed in the glandular epithelium, while no signal was detected
      after progesterone or estrogen treatment alone. By RT-PCR analysis, gp130 mRNA
      was detected in all of the uteri from day 1-8 of pregnancy, being at the highest
      level on day 4 of pregnancy. Additionally, a high level of LIFR and gp130 mRNA
      signal was detected in the decidua under artificial decidualization compared to
      the control uninjected horn. The co-expression of a high level of LIFR and gp130
      mRNA in the decidua may play a key role during the decidualization and
      placentation.

PMID- 12203825
TI  - Position-independent and tissue-specific expression of porcine whey acidic
      protein gene from a bacterial artificial chromosome in transgenic mice.
AB  - Silencing of transgenes is a frequent event after the random integration of
      foreign DNA in the host genome following microinjection. Long genomic fragments
      are expected to contain all the regulatory elements necessary to induce an
      appropriate expression of transgenes. A bacterial artificial chromosome
      containing the porcine wap gene with approximately 145 and 5 kb of 5'- and 3'
      flanking sequences, respectively, was microinjected into fertilized mouse
      ovocytes. In the six transgenic lines studied, expression was strictly specific
      to the mammary gland of lactating animals and was position-independent. Levels of
      exogenous porcine wap mRNA per copy compared favorably with the porcine wap mRNA
      yield in the mammary gland of a 9-day lactating pig. These findings suggest that
      this insert contained most if not all of the cis-acting elements involved in the
      full specific expression of the porcine wap gene. These elements constitute good
      candidates for directing the optimized expression of protein recombinant-encoding
      genes in the mammary gland of lactating animals.

PMID- 12203826
TI  - Mouse transgenic for murine oviduct-specific glycoprotein promoter-driven simian
      virus 40 large T-antigen: tumor formation and its hormonal regulation.
AB  - Transgenic mice were generated in which a 2.2-kb segment of the 5'-flanking
      sequence of the mouse oviduct-specific glycoprotein (OGP) gene was used to drive
      expression of the simian virus 40 large T antigen (Tag). These mice spontaneously
      developed tumors in the female reproductive tract. Analysis using reverse
      transcriptase-polymerase chain reaction showed that the 2.2-kb OGP 5'-flanking
      region drove Tag mRNA expression in the oviduct, uterus, vagina, and ovary, but
      not in other tissues. Histological and immunohistochemical analyses revealed that
      the tumor cells were distributed in the oviduct, endometrium, myometrium, and
      vagina; and had atypical features, abnormal mitosis, and Tag expression.
      Ovariectomy suppressed Tag expression, and thereby, blocked tumorigenesis in the
      transgenic mice. Estradiol administration to ovariectomized transgenic mice led
      to dramatic hyperplasia of the reproductive tract tissues in association with
      enhanced Tag expression, both in intensity and distribution. These results
      demonstrated that a 2.2-kb fragment of the 5'-flanking sequence of the mouse OGP
      gene was capable of directing the expression of Tag and inducing tumorigenesis in
      female reproductive tract tissues in an estrogen-dependent manner. Estrogen
      response elements present in the promoter region were functional in vivo. These
      transgenic mice represent a unique model, since they develop tumors in the
      oviducts as well as in other tissues derived from the Mullerian duct.

PMID- 12203827
TI  - Comparison between PMSG- and FSH-induced superovulation for the generation of
      transgenic rats.
AB  - Superovulation protocols using single injections of pregnant mare's serum
      gonadotropin (PMSG) or minipumps with follicle-stimulating hormone (FSH) were
      compared in immature Sprague-Dawley (SD) rats. We used the following criteria:
      total number of ova, rate of fertilization, in vitro embryo development,
      sensitivity of zygotes to the microinjection of foreign DNA into the pronucleus,
      and their in-vivo development after transplantation into the oviduct of a
      recipient. Female SD rats were stimulated with 15 IU PMSG or 10 mg FSH followed
      by the injection of human chorionic gonadotropin (hCG) at doses of 20 and 30 IU
      per female. After hCG administration, they were mated with males of the same
      strain and sacrificed on day 1 of pregnancy. The percentage of mated animals and
      the fertilization rate was similar in all groups. In rats given PMSG, the number
      of ovulated zygotes was hCG dose-dependent. In contrast, the dose of hCG did not
      influence the efficiency of superovulation in rats given FSH, which was equal to
      PMSG-treated rats at the optimal dose of hCG. The rates of in vitro blastocyst
      development (31.4 and 23.3%) and the resistance to microinjection into the
      pronucleus did also not differ significantly between zygotes of both studied
      groups. The proportion of offspring developing from microinjected zygotes after
      oviduct transfer (26.2 and 26.8%, respectively) and the rate of transgene
      integration per newborns (7.3 and 4.9%, respectively) was similar in both
      experimental groups. The results of this study demonstrate that superovulation of
      immature SD rats by PMSG is equally effective as FSH treatment and, thus,
      preferable for transgenic rat technology due to the lower costs and easier
      handling.

PMID- 12203828
TI  - Differential cytoplast requirement for embryonic and somatic cell nuclear
      transfer in cattle.
AB  - Effective activation of a recipient oocyte and its compatibility with the nuclear
      donor are critical to the successful nuclear reprogramming during nuclear
      transfer. We designed a series of experiments using various activation methods to
      determine the optimum activation efficiency of bovine oocytes. We then performed
      nuclear transfer (NT) of embryonic and somatic cells into cytoplasts presumably
      at G1/S phase (with prior activation) or at metaphase II (MII, without prior
      activation). Oocytes at 24 hr of maturation in vitro were activated with various
      combinations of calcium ionophore A23187 (A187) (5 microM, 5 min), electric pulse
      (EP), ethanol (7%, 7 min), cycloheximide (CHX) (10 micro g/ml, 6 hr), and then
      cultured in cytochalasin D (CD) for a total of 18 hr. Through a series of
      experiments (Exp. 1-4), an improved activation protocol (A187/EP/CHX/CD) was
      identified and used for comparison of NT efficiency of embryonic versus somatic
      donor cells (Exp. 5). When embryonic cells from morula and blastocysts (BL) were
      used as nuclear donors, a significantly higher rate of blastocyst development
      from cloned embryos was obtained with G1/S phase cytoplasts than with MII-phase
      cytoplasts (36 vs. 11%, P < 0.05). In contrast, when skin fibroblasts were used
      as donor cells, the use of an MII cytoplast (vs. G1/S phase) was imperative for
      blastocyst development (30 vs. 6%, P < 0.05). Differential staining showed that
      parthenogenetic, embryonic, and somatic cloned BL contained 26, 29, and 33%
      presumptive inner cell mass (ICM) cells, respectively, which is similar to that
      of frozen-thawed in vivo embryos at a comparable developmental stage (23%). These
      data indicate that embryonic and somatic nuclei require different recipient
      cytoplast environment for remodeling/ reprogramming, and this is likely due to
      the different cell cycle stage and profiles of molecular differentiation of the
      transferred donor nuclei.

PMID- 12203829
TI  - Fine structure of leydig and sertoli cells in the testis of immature and mature
      spotted ray Torpedo marmorata.
AB  - An ultrastructural investigation revealed the presence of true Leydig cells in
      the testis of sexually mature specimens of Torpedo marmorata. They showed the
      typical organization of steroid-hormone-producing cells, which, however, changed
      as spermatocysts approached maturity. In fact, they appeared as active cells
      among spermatocysts engaged in spermatogenesis, while in regions where
      spermiation occurred, they progressively regressed resuming the fibroblastic
      organization typically present in the testis of immature specimens. Such
      observations strongly suggest that these cells might be engaged in
      steroidogenesis and actively control spermatogenesis. Sertoli cells, too,
      appeared to play a role in spermatogenesis control, since, like Leydig cells,
      they showed the typical aspect of steroidogenic cells. In addition, the presence
      of gap junctions between Sertoli cells suggests that their activity might be
      coordinated. After sperm release, most Sertoli cells were modified and, finally,
      degenerated, but few of them changed into round cells (cytoplasts) or round cell
      remnants, which continued their steroidogenic activity within the spermatocyst
      and the genital duct lumen. From the present observations, it can be reasonably
      concluded that, in T. marmorata, spermatogenesis depends on both Leydig and
      Sertoli cells, and, as postulated by Callard (1991), in cartilaginous fish, the
      function of the Leydig cells as producers of steroids might be more recent and
      subsequent to that of Sertoli cells. In this regard, it is noteworthy that, in
      immature males, when Leydig cells showed a fibroblastic organization, Sertoli
      cells already displayed the typical organization of a steroidogenic cell.

PMID- 12203830
TI  - Control of the annual testicular cycle of the marbled-newt by p53, p21, and Rb
      gene products.
AB  - p53, p21, and Rb are proteins with an important role in cell-cycle control. The
      expression and distribution of these gene products and the apoptotic rate were
      studied in the marbled-newt testis along the annual cycle to know the role of
      these factors in the control of spermatogenesis and glandular tissue formation.
      The study was carried out using Western blot analysis and immunohistochemistry.
      The results differed from those, previously reported in mammals showing constant
      spermatogenesis. Greater expression of p53 and p21 was found in the quiescence
      period and was detected in PCGs (primordial germ cells), spermatogonia,
      follicular, interstitial cells, and glandular tissue. Greater expression of Rb
      and phosph-Rb was present in the proliferation period, in PCGs, and
      spermatogonia. Apoptosis was only detected in secondary spermatogonia (quiescence
      and spermiogenesis periods) and primary spermatocytes (proliferation and
      spermiogenesis periods). In the quiescence period, the increase in p53 expression
      activates p21 expression, which inhibits Rb phosphorylation and arrests the cell
      cycle in G1. In the proliferation period and, in a lesser degree, in the
      spermiogenesis period, the expressions of p53 and p21 decrease and phosph-Rb
      increases, enhancing cell proliferation. These gene products do not seem to be
      related to apoptosis.

PMID- 12203831
TI  - Effects of beta-endorphin and Naloxone on in vitro maturation of bovine oocytes.
AB  - Bovine cumulus-oocyte complexes (COCs) and mural granulosa cells express the mRNA
      coding for the micro-opioid receptor. The addition of beta-endorphin (beta-end)
      to oocytes cultured in hormonally-supplemented in vitro maturation (IVM) medium
      had no effect on the rates of oocytes reaching the metaphase II (MII) stage, but
      significantly decreased the maturation rate (P < 0.05) and arrested oocytes at
      metaphase I (MI) after culture in hormone-free medium (P < 0.001). Naloxone (Nx)
      reverted this inhibitory effect of beta-end. Moreover, Nx "per se" showed a dose
      dependent dual effect. When added at high concentration (10 x (-3) M), it
      significantly reduced the rate of oocytes in MII (P < 0.001), thus increasing the
      rate of oocytes arrested in MI. However, Nx added at low concentration (10 x (-8)
      M) significantly increased oocyte maturation (P < 0.001). High concentration of
      Nx induced an increase in both intracellular calcium concentration ([Ca(2+)](i))
      and in the activity of the mitogen-activated protein kinase (MAPK) also called
      extracellular-regulated kinase (ERK) in cumulus cells of bovine COCs. Blocking
      the rise in [Ca(2+)](i) with the calcium chelator acetoxymethylester-derived form
      of bis (o-aminophenoxy) ethane-N,N,N',N'-tetraacetic acid (BAPTA-AM) reversed the
      Nx-dependent inhibition of meiotic maturation observed at high Nx concentrations.
      Whereas blocking ERK with the MAPK/ERK kinase (MEK) inhibitor, PD98059, had no
      effect on this process. Therefore, we concluded that the mocro-opioid receptor,
      by inducing [Ca(2+)](i) increase, participates in the cumulus-oocyte coupled
      signaling associated with oocyte maturation.

PMID- 12203832
TI  - Link protein as an enhancer of cumulus cell-oocyte complex expansion.
AB  - To investigate the specific components involved in regulating cumulus cell-oocyte
      complex (COC) expansion in an in vitro mouse experiment, freshly-isolated COC
      were cultured in the presence of various combinations of FSH (1.0 microg/ml),
      proteins of the inter-alpha-inhibitor (I alpha I) family (a light chain, also
      known as bikunin, heavy chains [HC1 + HC2] and I alpha I [0.01-2.0 microg/ml])
      and link protein (LP) (0.016-10 microg/ml) for 24 h and were observed for
      expansion of their cumulus cells (percent of COC with + 3 and + 4 expansion and
      average projected area). The COC were videotaped in real time at the initiation
      of culture and after 24 h of culture. FSH alone did not stimulate cumulus
      expansion under serum-free conditions; however, treatment with I alpha I (0.1-2.0
      microg/ml) or heavy chains (10 microg/ml), but not bikunin (10 micro g/ml), in
      the presence of FSH significantly increased COC expansion, with maximal promotion
      occurring at 1.0 microg/ ml of I alpha I. Addition of LP (2.0 micro g/ml) to the
      medium containing I alpha I (1.0 microg/ml) and FSH resulted in significantly
      higher expansion levels than were observed in response to I alpha I alone,
      although LP alone (10 microg/ml) had no or very little effect by itself. Anti-I
      alpha I or anti-LP polyclonal antibody, which inhibits binding of I alpha I and
      LP, respectively, to hyaluronic acid (HA), markedly reduced expansion of the
      surrounding cumulus cell extracellular matrices. Therefore, in vitro, LP might
      serve, in part, to enhance the COC expansion possibly by stabilizing HA-I alpha I
      (or heavy chains) complex on the surrounding cumulus cell matrices.

PMID- 12203833
TI  - Evaluation of segregation patterns of 21;21 Robertsonian translocation along with
      sex chromosomes and interchromosomal effects in sperm nuclei of carrier by FISH
      technique.
AB  - Meiotic segregation patterns of carriers of Robertsonian translocations (RT) are
      important for assessing the risk of unbalanced forms. We investigated the ratio
      of sperm with t(21;21) to sperm with nullisomy for chromosome 21; the segregation
      of the t(21;21) along with sex chromosomes, and also interchromosomal effects on
      chromosome 10 by using three color fluorescence in situ hybridization (FISH) with
      telomere specific (Tel 21q) and centromere-specific alpha satellite probes for
      chromosomes X, Y, and 10. The percentage of cosegregation of t(21;21) with sex
      chromosomes (49.50%) and without sex chromosomes (46.98%) was not significant.
      There are no significant differences between the percentages of cosegregation of
      t(21;21) with chromosome X (23.36%) and with chromosome Y (26.16%). No evidence
      of an interchromosomal effect on chromosome 10 was detected, the percentage of
      chromosome 10 aneuploidy being similar to that in controls. In addition, the
      frequency of diploid sperm nuclei was not significantly higher in the carrier
      (0.32%) than in the controls (0.44%) (P > 0.05). The sex ratio was similar within
      the carrier and the controls and between the carrier and the control. Three color
      FISH analysis, using different probe combinations, seems a rapid and accurate
      tool for direct analysis of meiotic segregation product.

PMID- 12203834
TI  - Cross-linking of ZP2 and ZP3 by transglutaminase is required for the formation of
      the outer layer of fertilization envelope of carp egg.
AB  - A transglutaminase (TGase) cDNA was cloned from carp ovary. It was highly
      homologous to zebrafish TGase. Immunoblot and enzymatical assay showed that TGase
      was present on the chorion and in the cytoplasm of carp eggs. Addition of TGase
      inhibitor, cadaverine or ethylene diaminetetracetic acid (EDTA) to the cortical
      reaction medium impaired the formation of the outer layer of fertilization
      envelope (FE(o)), the adhesive structure of carp egg. Fibroin-like substance
      (FLS), cystatin, cathepsin-like substance (CLS), and FEO-1 were the components of
      FE(o), wherein the majority of the former three were conjugated to form
      macromolecules of 90-205 kDa while the latter one was present in monomer of 22
      kDa. Cadaverine interfered slightly the discharge of FLS conjugates out of the
      perivitelline space (PVS) but affected profoundly the recruitment of FLS
      conjugates to FE, whereas EDTA completely inhibited both the release and the
      recruitment of FLS conjugates to FE. Both EDTA and cadaverine did not inhibit the
      discharge of FEO-1 out of PVS but could inhibit the recruitment of FEO-1 to FE.
      The mechanism was studied. ZP2 and ZP3, the major constituents of inner layer of
      FE, were cross-linked during cortical reaction, which rendered FE hardened. In
      the presence of EDTA, the cross-linking of ZP2 and ZP3 were inhibited, thus FE
      remained soft. The PVS of an egg with a hardened FE was less expanded than an egg
      with a soft FE. It was assumed that a less expanded PVS would generate a higher
      fluid pressure than a more expanded PVS did. Therefore, the transportation of the
      macromolecules such as the FLS-cystatin-CLS conjugates out of PVS was facilitated
      in control and cadaverine-treated eggs whose FE were hardened but was blocked in
      EDTA-treated eggs whose FE were unhardened. On the other hand, the transportation
      of small molecules such as FEO-1 out of FE was not restrained, so they were
      discharged out of the PVS of the control and TGase inhibitor-treated eggs. In
      addition, TGase activity was also required for the recruitment of FLS conjugates
      to FE.

PMID- 12203835
TI  - Capacitation state-dependent changes in adenosine receptors and their regulation
      of adenylyl cyclase/cAMP.
AB  - This study was designed to localize adenosine receptors and to provide evidence
      that specific receptors are active only in either uncapacitated or capacitated
      mouse spermatozoa, where they play a role in regulating cAMP production. Using
      specific antibodies, stimulatory A(2A) receptors were localized primarily on the
      acrosomal cap region and the flagellar principal piece. Interestingly, the
      staining was much more pronounced in uncapacitated than in capacitated
      spermatozoa, suggesting capacitation-dependent changes in epitope accessibility.
      A(1) receptors showed a very similar distribution, but the staining was markedly
      greater in capacitated than in uncapacitated cells. After addition of purified
      decapacitation factor (DF) to capacitated cells, strong staining for A(2A) was
      regained, suggesting reversibility in epitope accessibility. Chlortetracycline
      analysis revealed that an agonist specific for A(2A) receptors had no detectable
      effect on capacitated cells, but after DF-induced decapacitation, the agonist
      then stimulated capacitation. That agonist also significantly stimulated cAMP
      production in uncapacitated cells, had no effect on capacitated cells, but
      regained the ability to stimulate cAMP in the latter following DF treatment. In
      contrast, an A(1) agonist inhibited cAMP in capacitated cells. These results
      indicate that specific adenosine receptors function in a reversible manner in one
      or other capacitation state, resulting in regulation of cAMP.

PMID- 12203836
TI  - Molecular cloning and sequencing of cDNA encoding for human FA-1 antigen.
AB  - The cDNA encoding for the human FA-1 sperm antigen was cloned and sequenced from
      the in-house constructed subtractive human testis cDNA expression library in
      lambda Ziplox using the FA-1 monoclonal antibody (mAb). The full--length sequence
      was obtained by using the 5' rapid amplification of 5'-cDNA end (5'-RACE)
      procedure. It is 1,576-bp long, and has an open reading frame (ORF) of 283 amino
      acids (aa) with the first ATG Met start codon at nucleotide (nt) 57 and the stop
      codon TAG at nt 906. It has two termination codons at the 5' end before the ATG
      start codon. The translated protein has a calculated molecular weight of 32.1 kDa
      and estimated isoelectric point (pI) of 11.59. It has one potential N-linked
      glycosylation site and one tyrosine phosphorylation site, besides several O
      linked glycosylation and serine and threonine phosphorylation sites.
      Hydrophilicity analysis of the deduced aa sequence showed it to be a membrane
      anchored protein. Extensive computer search in the database did not identify any
      known nt/aa sequence having homology with FA-1 cDNA or deduced aa, indicating it
      to be a novel gene. The Northern blot and reverse transcription-polymerase chain
      reaction (RT-PCR)-Southern blot analyses indicated the testis-specific expression
      of FA-1 antigen at the mRNA level. The ORF of the FA-1 was subcloned into pGEX-
      1lambda T for expression. The expressed FA-1 recombinant protein had a molecular
      size of approximately 40 kDa, and was recognized by the FA-1 mAb, and not by the
      myeloma control Ig. The rabbit antibodies (Ab) raised against the recombinant (r)
      FA-1 antigen recognized the rFA-1 antigen as well as the native (n) FA-1 antigen.
      The rFA-1 Ab specifically recognized a protein band of approximately 50 kDa in
      human testis extract in the Western blot involving 11 types of human tissue
      extracts, indicating the testis-specific expression of FA-1 at the protein level.
      The Ab showed binding with live and methanol-fixed human sperm at the post
      acrosomal, mid-piece, and tail regions. The Ab caused a significant (P < 0.001)
      and concentration-dependent inhibition of human sperm capacitation/acrosome
      reaction by blocking tyrosine phosphorylation of the FA-1 antigen. The sperm
      specific human FA-1 recombinant antigen may find applications in
      immunocontraception, and diagnosis and treatment of immunoinfertility in humans.

PMID- 12203838
TI  - Identification of epitope-like consensus motifs using mRNA display.
AB  - The mRNA display approach to in vitro protein selection is based upon the
      puromycin-mediated formation of a covalent bond between an mRNA and its gene
      product. This technique can be used to identify peptide sequences involved in
      macromolecular recognition, including those identical or homologous to natural
      ligand epitopes. To demonstrate this approach, we determined the peptide
      sequences recognized by the trypsin active site, and by the anti-c-Myc antibody,
      9E10. Here we describe the use of two peptide libraries of different diversities,
      one a constrained library based on the trypsin inhibitor EETI-II, where only the
      six residues in the first loop were randomized (6.4 x 10(7) possible sequences,
      6.0 x 10(11) sequences in the library), the other a linear-peptide library with
      27 randomized amino acids (1.3 x 10(35) possible sequences, 2 x 10(13) sequences
      in the library). The constrained library was screened against the natural target
      of wild-type EETI, bovine trypsin, and the linear library was screened against
      the anti-c-myc antibody, 9E10. The analysis of selected sequences revealed
      minimal consensus sequences of PR(I,L,V)L for the first loop of EETI-II and LISE
      for the 9E10 epitope. The wild-type sequences, PRILMR for the first loop of EETI
      II and QKLISE for the 9E10 epitope, were selected with the highest frequency, and
      in each case the complete wild-type epitope was selected from the library.

PMID- 12203837
TI  - Conformational analysis of bacterial cell wall peptides indicates how particular
      conformations have influenced the evolution of penicillin-binding proteins, beta
      lactam antibiotics and antibiotic resistance mechanisms.
AB  - Our aim was to use a conformational analysis technique developed for peptides to
      identify structural relationships between bacterial cell wall peptides and beta
      lactam antibiotics that might help to explain their different actions as
      substrates and inhibitors of penicillin binding proteins (PBPs). The
      conformational forms of the model cell wall peptide Ac-L-Lys(Ac)-D-Ala-D-Ala are
      described by just a few backbone torsion combinations: three C-terminal
      carboxylate regions, with Tor8 (psi(i+1)) ranges of D3 region (50 degrees to 70
      degrees ), D6 region (140 degrees to 170 degrees ) and D9 region (-50 degrees to 
      70 degrees ) are combined with either of two Tor6 (phi(i))-Tor4 (psi(i))
      combinations, C4 region (-50 degrees to -80 degrees ) with B8 region (-40 degrees
      to -70 degrees ) or C11 region (30 degrees to 50 degrees ) with B2 region (30
      degrees to 70 degrees ). From these results, and comparisons with conformational
      analyses of various beta-lactams and Ac-L-Lys(Ac)-D-Ala-D-Lac, it is concluded
      that molecular recognition of cell wall peptide substrates by PBPs requires
      conformers with backbone torsion angles of D3C4B8. beta-Lactam antibiotics are
      constrained compounds with fewer conformational forms; these match well the
      backbone torsions of cell wall peptides at D3C4, allowing their recognition and
      acylation by PBPs, whereas their unique Tor4 produces differently orientated CO
      and N atoms that appear to prevent subsequent deacylation, leading to their
      action as suicide substrates. The results are also related to the selective
      pressures involved in evolution of beta-lactamases from PBPs. From analysis of
      conformers of Ac-L-Lys(Ac)-D-Ala-D-Ala and the vancomycin-resistant analogue Ac-L
      Lys(Ac)-D-Ala-D-Lac, it is concluded that vancomycin may recognise D6C11B2
      conformers, giving it complementary substrate specificity to PBPs. This approach
      could have applications in the rational design of antibiotics targeted against
      PBPs and their substrates.

PMID- 12203839
TI  - Analysis of the interaction between the aspartic peptidase inhibitor SQAPI and
      aspartic peptidases using surface plasmon resonance.
AB  - Aspartic peptidase inhibitors, which are themselves proteins, are strong
      inhibitors (small inhibition constants) of some aspartic peptidases but not
      others. However, there have been no studies of the kinetics of the interaction
      between a proteinaceous aspartic peptidase inhibitor and aspartic peptidases.
      This paper describes an analysis of rate constants for the interaction between
      recombinant squash aspartic peptidase inhibitor (rSQAPI) and a panel of aspartic
      peptidases that have a range of inhibition constants for SQAPI. Purified rSQAPI
      completely inhibits pepsin at a 1:1 molar ratio of pepsin to rSQAPI monomer
      (inhibition constant 1 nM). The interaction of pepsin with immobilized rSQAPI, at
      pH values between 3.0 and 6.0, was monitored using surface plasmon resonance.
      Binding of pepsin to rSQAPI was slow (association rate constants ca 10(4)M (-1)s(
      1)), but rSQAPI was an effective pepsin inhibitor because dissociation of the
      rSQAPI-pepsin complex was much slower (dissociation rate constants ca 10(-4)s(
      1)), especially at low pH values. Similar results were obtained with a His-tagged
      rSQAPI. Strong inhibition (inhibition constant 3 nM) of one isoform (rSap4) of
      the family of Candida albicans-secreted aspartic peptidases was, as with pepsin,
      characterized by slow binding of rSap4 and slower dissociation of the rSap4
      inhibitor complex. In contrast, weaker inhibition of the Glomerella cingulata
      secreted aspartic peptidase (inhibition constant 7 nM) and the C. albicans rSap1
      and Sap2 isoenzymes (inhibition constants 25 and 400 nM, respectively) was, in
      each case, characterized by a larger dissociation rate constant.

PMID- 12203840
TI  - A complete substitutional analysis of VIP for better tumor imaging properties.
AB  - Since numerous tumor cells overexpress the vasoactive intestinal peptide (VIP)
      receptor subtype 1 (VPAC(1)), VIP-dye conjugates would be useful as contrast
      agents for in vivo imaging. However, proteolytic degradation of VIP in vivo
      limits their diagnostic use and highlights the need for structurally optimized
      VIP derivatives with improved pharmacokinetics. Here, we applied parallel nano
      synthesis of cleavable peptides on cellulose membranes to perform a complete VIP
      substitutional analysis. The resulting 504 different VIP-dye analogs were tested
      for cell binding by flow cytometry. They provided a detailed analysis of amino
      acid positions essential for binding to VPAC(1) overexpressing cells. A
      generalized VIP-dye binding motif derived from the substitutional analysis
      results served as a reference point for further optimization. An [Arg8]-VIP-dye
      analog showed increased stability towards proteolytic degradation, good tumor-to
      tissue contrast in mice and a longer half-life in vivo.

PMID- 12203841
TI  - Comparative structural connectivity spectra analysis (CoSCoSA) models of steroids
      binding to the aromatase enzyme.
AB  - A method that combines NMR spectral and structural information into a constructed
      three-dimensional (3D)-connectivity matrix is developed for modeling biological
      binding activity of small molecules. The 3D-connectivity matrix for a molecule is
      defined by associating the distances between all possible carbon-to-carbon
      connections with their assigned carbon NMR chemical shifts. In this project we
      selected from the total 3D-connectivity matrix a subset, the two-dimensional (2D)
      (13)C-(13)C COSY and a theoretical long range 2D (13)C-(13)C distance
      connectivity spectral plane. Patterns of (13)C chemical shifts observed at these
      two relative distances for 50 steroids were used to produce a mathematical
      relationship for the steroids' relative binding affinity (pK(i)) to the aromatase
      enzyme. We call this technique comparative structural connectivity spectra
      analysis (CoSCoSA) modeling. Using combinations of the 2D COSY and 2D long-range
      distance spectra as modeling parameters, we built four CoSCoSA models. One model
      was made from the 2D COSY spectra alone and another was developed using only the
      2D long-range distance spectra. Then the COSY and long-distance spectra were
      combined in two different ways: starting with the combined principal components
      (PCs) from the separately calculated COSY and distance spectra or using the
      combined raw spectra (3D). The best CoSCoSA model was based on the combined PCs
      from COSY and distance spectra. This model had an r(2) of 0.96 and a leave-one
      out cross-validation (q(2)) of 0.92. In general CoSCoSA modeling combines the
      quantum mechanical information inherent in NMR chemical shifts with internal
      molecular atom-to-atom distances to give a reliable and straightforward basis for
      predictive modeling. The technique has the flexibility and accuracy to outperform
      not only the cross-validated variance q(2) of previously published quantitative
      structure-activity relationships (QSAR) but also those obtained by related
      quantitative spectral data-activity relationships (QSDARs) lacking connectivity
      dimensions.

PMID- 12203842
TI  - Anti-U1A monoclonal antibodies recognize unique epitope targets of U1A which are
      involved in the binding of U1 RNA.
AB  - The U1A (or nRNP A) protein is known to play a critical role in eukaryotic pre
      mRNA splicing and polyadenylation. Previous studies revealed that several mouse
      monoclonal antibodies (MAbs) recognized U1A as part of the U1snRNP, while MAb
      12E12 was unique in that it recognized an epitope that is masked when U1A is
      bound to U1 RNA. In order to further characterize and understand the antigenic
      targets of these MAbs, we undertook fine specificity epitope mapping studies.
      Anti-U1A MAbs 12E12 and 10E3 each recognize unique peptides from the U1A protein.
      Interestingly, these MAbs recognize epitopes which have been shown to be
      antigenic in human autoimmune diseases. When superimposed on structures of U1A
      derived from crystal and NMR data, the major epitope recognized by 12E12 (amino
      acids 103-108) localizes to the surface of the U1A molecule. The 12E12 epitope is
      immediately adjacent to a helix which probably reacts to U1 RNA binding by
      undergoing a conformational change. This modification of structure effectively
      masks the 12E12 epitope, thus preventing binding of the monoclonal to U1A/U1 RNA
      complexes. These findings suggest that the structure of the U1A protein may be
      different when not part of the U1snRNP.

PMID- 12203843
TI  - Transmission of tuberculosis from adults to children in a Paris suburb.
AB  - Tuberculosis in children is often acquired by contact with a family or household
      member. The aim of our study was to evaluate risk factors for latent infection
      and active disease in exposed children in a suburb of Paris. We examined medical
      records for the period 1997-2000 at six departmental centers for medical
      prevention in Val de Marne. Thirty-nine patients aged 18 years or more with M.
      tuberculosis-positive sputum samples, and living with children or adolescents,
      were identified. Ninety-one children, aged 3 months-17 years, were exposed to
      these index cases. All the children initially underwent a tuberculin skin test
      and chest radiography, and children with no criteria for latent infection or
      active disease at time of initial evaluation were asked to attend a second
      evaluation 3 months later. Overall, 20 of the 91 (22%) children were infected,
      including 4 children identified only at the second evaluation. Eight (40%) of the
      20 infected children had active disease, including 2 of the 4 children identified
      at the second evaluation. The risk of infection was not influenced by the
      children's age, but was significantly associated with three characteristics of
      the adult cases, i.e., age younger than 40 years, presence of cavitary lesions,
      and smears with more than 100 bacilli per microscopic field. In conclusion, our
      results call for early examination of all exposed children, in order to prevent
      infection and progression to active disease, and for a routine second evaluation
      after the adult contact has ended.

PMID- 12203844
TI  - Outcome in adulthood of asymptomatic airway hyperresponsiveness in childhood: a
      longitudinal population study.
AB  - The clinical outcome of asymptomatic airway hyperresponsiveness (AHR) first
      detected in childhood is sparsely reported, with conflicting results. We used a
      birth cohort of 1,037 children followed to age 26 years to assess the clinical
      outcome of asymptomatic AHR to methacholine first documented in study members at
      age 9 years. Of 547 study members who denied wheezing symptoms ever at age 9
      years, 41 (7.5%) showed AHR. Forty showed methacholine responsiveness, with a
      provocation concentration of methacholine that elicited a 20% drop in forced
      expired volume in 1 sec (PC(20)) < or = 8 mg/mL, and one had baseline airway
      obstruction with a bronchodilator response exceeding 10%. Of these 41 study
      members, 18 (44%), 11 (27%), and 4 (10%) maintained AHR in 1, 2, and 3 later
      assessments, respectively, while 23 (56%) manifested AHR only at age 9. Compared
      with asymptomatic study members without AHR, those with asymptomatic AHR at age 9
      years were more likely to report asthma and wheeze at any subsequent assessment,
      were more likely to have high IgE levels and eosinophils at ages 11 and 21, and
      more often demonstrated positive responses to skin allergen testing at ages 13
      and 21 years. Persistent AHR at later assessments increased these likelihoods
      further.In conclusion, asymptomatic children with AHR are more likely to develop
      asthma and atopy later in life compared with asymptomatic children without AHR.
      Persistent AHR, even though initially asymptomatic, was associated with an even
      greater increased risk of development of asthma. We suggest that rather than
      considering AHR as a marker of asthma, it should be regarded as a parallel
      pathological process that may lead to subsequent symptoms and clinical evidence
      of asthma.

PMID- 12203845
TI  - Extrathoracic airway responsiveness in children with asthma-like symptoms,
      including chronic persistent cough.
AB  - Asthma-like symptoms, including chronic persistent cough, are not always specific
      for classical asthma. In order to investigate whether assessment of extrathoracic
      airway hyperresponsiveness (EAHR) during methacholine bronchial challenge helped
      in the evaluation of pediatric patients with asthma-like symptoms such as chronic
      cough, we examined 133 consecutive, unselected patients (mean age, 10.06 +/- 2.16
      years) who had neither established asthma nor bronchial obstruction previously.
      We recorded the forced mid-inspiratory flow (FIF(50)) as an index of
      extrathoracic airway narrowing. In addition, a 25% decrease in FIF(50)
      (PD(25)FIF(50)) below the cutoff concentration of < or = 8 mg/mL methacholine was
      assumed to indicate EAHR. According to the methacholine response, 81 patients had
      EAHR, and 41 of them had combined EAHR and bronchial hyperresponsiveness (BHR);
      39 patients had only BHR. Airway hyperresponsiveness was not demonstrated in 13
      patients and not in any of the control children. When patients with cough as the
      sole presenting symptom (60.9%) were compared with those with cough and wheeze
      (20.3%), those with cough alone had a significantly greater probability of having
      EAHR (OR, 4.16; 95% CI, 1.32-13.13) and a lower probability of having BHR (OR,
      0.70; CI, 0.25-1.95) than those with cough and wheeze. Patients with cough,
      wheeze, and dyspnea (18.8%) had a significantly greater chance of having BHR than
      those with cough alone (OR, 5.08; CI, 1.55-16.64). Patients with cough and wheeze
      as compared with those with cough, wheeze, and dyspnea had significantly greater
      probability of having both EAHR and BHR (OR, 4.71; CI, 1.94-11.47). In order to
      ascertain the clinical relevance of EAHR, we assessed in the second part of the
      study whether the effects of treatment of the underlying disease would result in
      relief of airway hyperresponsiveness. Rhinosinusitis and perennial allergic
      rhinitis accounted for EAHR in 71 patients, and 34 of them also demonstrated BHR.
      They received specific therapy for their upper airway diseases for 4 weeks.
      Compared with values before treatment, FIF(50) and forced expiratory volume in 1
      sec (FEV(1)) did not change significantly. The dose of methacholine causing a 20%
      fall in FEV(1) (PD(20)FEV(1)) and PD(25)FIF(50) values were significantly
      increased from 2.40 +/- 1.39 to 4.22 +/- 1.13 mg /mL (P < 0.001) and from 1.03 +/
      1.75 to 8.71 +/- 1.21 mg /mL (P < 0.0001), respectively. We conclude that
      measurements of EAHR and BHR are the most important ways to evaluate children
      with asthma-like symptoms, including chronic persistent cough when chest X-rays
      and pulmonary function tests remain within normal limits. Therefore, empirical
      treatment is not necessary when these investigations are available. Our results
      suggest that specific treatment of inflammation in the upper airways reversed
      persistant cough, and may play an important role in modulating lower airways
      responsiveness in patients with concomitant BHR.

PMID- 12203846
TI  - Incidence of respiratory syncytial virus-related hospitalizations in high-risk
      children: follow-up of a national cohort of infants treated with Palivizumab as
      RSV prophylaxis.
AB  - The prophylactic administration of Palivizumab, a monoclonal antibody binding the
      respiratory syncytial virus (RSV) fusion protein, was recently shown to
      significantly decrease the incidence of RSV-related hospitalizations among high
      risk children (IMpact-RSV trial). While awaiting marketing authorization in
      France and through a cohort of patients' name-based national program temporarily
      authorized by the French Drug Agency, a prospective register of all Palivizumab
      treated patients in France was set up during the epidemic season 1999-2000. Based
      on this register, this study was carried out to evaluate the incidence of RSV
      related hospitalizations and the safety of prophylaxis among a national cohort of
      children at high-risk of severe RSV disease. During the study period, guidelines
      issued by the French Pediatric Society recommended prophylaxis for children
      either aged less than 6 months at inclusion and born at less than 33 weeks of
      gestation with a history of bronchopulmonary dysplasia (BPD) at 28 days of life,
      or aged less than 2 years, born at less than 36 weeks of gestation, and having
      required treatment for BPD over the previous 6 months. Once included in the
      program, investigators were to prospectively report the clinical and demographic
      characteristics of children, all hospitalizations, and reasons for the
      hospitalizations. Five hundred and sixteen children were treated with 1-5 monthly
      doses. The median gestational age was 28 weeks, and children born at less than 33
      weeks of gestation accounted for 88% of the cohort. The prevalence of BPD was
      81%. Ninety children were hospitalized for respiratory illness. In 39 children,
      hospitalizations were attributed to RSV (7.6% of the total cohort). Among those
      39 children, 10 (1.9% of the total cohort) required admission into an intensive
      care unit, and 4 required mechanical ventilation. No deaths or serious adverse
      events attributable to RSV infection or Palivizumab treatment were reported. We
      conclude that the RSV-related hospitalization rate in this high-risk cohort was
      comparable to the rate observed in the subgroup of Palivizumab-prophylaxed
      children with BPD in the IMpact-RSV trial.

PMID- 12203847
TI  - Series of laryngomalacia, tracheomalacia, and bronchomalacia disorders and their
      associations with other conditions in children.
AB  - Laryngomalacia, bronchomalacia, and tracheomalacia are commonly seen in pediatric
      respiratory medicine, yet their patterns and associations with other conditions
      are not well-understood. We prospectively video-recorded bronchoscopic data and
      clinical information from referred patients over a 10-year period and defined
      aspects of interrelationships and associations. Two hundred and ninety-nine cases
      of malacia disorders (34%) were observed in 885 bronchoscopic procedures. Cough,
      wheeze, stridor, and radiological changes were the most common symptoms and
      signs. The lesions were most often found in males (2:1) and on the left side
      (1.6:1). Concomitant malacia lesions ranged from 24% for
      laryngotracheobronchomalacia to 47% for tracheobronchomalacia. The lesions were
      found in association with other disorders such as congenital heart disorders
      (13.7%), tracheo-esophageal fistula (9.6%), and various syndromes (8%). Even
      though the understanding of these disorders is in its infancy, pediatricians
      should maintain a level of awareness for malacia lesions and consider the
      possibility of multiple lesions being present, even when one symptom predominates
      or occurs alone.

PMID- 12203848
TI  - Are tidal volume measurements in neonatal pressure-controlled ventilation
      accurate?
AB  - Bedside pulmonary mechanics monitors (PMM) have become useful in ventilatory
      management in neonates. These monitors are used more frequently due to recent
      improvements in data-processing capabilities. PMM devices are often part of the
      ventilator or are separate units. The accuracy and reliability of these systems
      have not been carefully evaluated. We compared a single ventilatory parameter,
      tidal volume (V(t)), as measured by several systems. We looked at two
      freestanding PMMs: the Ventrak Respiratory Monitoring System (Novametrix,
      Wallingford, CT) and the Bicore CP-100 Neonatal Pulmonary Monitor (Allied Health
      Care Products, Riverside, CA), and three ventilators with built-in PMM: the VIP
      Bird Ventilator (Bird Products Corp., Palm Springs, CA), Siemens Servo 300A
      (Siemens-Elema AB, Solna, Sweden), and Drager Babylog 8000 (Drager, Inc.,
      Chantilly, VA). A calibrated syringe (Hans Rudolph, Inc., Kansas City, MO) was
      used to deliver tidal volumes of 4, 10, and 20 mL to each ventilator system
      coupled with a freestanding PMM. After achieving steady state, six consecutive
      V(t) readings were taken simultaneously from the freestanding PMM and each
      ventilator. In a second portion of the bench study, we used pressure-control
      ventilation and measured exhaled tidal volume (V(te)) while ventilating a Bear
      Test Lung with the same three ventilators. We adjusted peak inspiratory pressure
      (PIP) under controlled conditions to achieve the three different targeted tidal
      volumes on the paired freestanding PMM. Again, six V(te) measurements were
      recorded for each tidal volume. Means and standard deviations were calculated.The
      percentage difference in measurement of V(t) delivered by calibrated syringe
      varied greatly, with the greatest discrepancy seen in the smallest tidal volumes,
      by up to 28%. In pressure control mode, V(te) as measured by the Siemens was
      significantly overestimated by 20-95%, with the biggest discrepancy at the
      smallest V(te), particularly when paired with the Bicore PMM. V(te), as measured
      by the VIP Bird and Drager paired with the Ventrak PMM, had a tendency to
      underestimate V(t) by up to 25% at the smallest V(te). However, when paired with
      the Bicore PMM, these same two ventilators read over target by up to 18%. Under
      controlled laboratory conditions, we demonstrated that true delivered V(te), as
      measured by the three ventilators and two freestanding PMM, differed markedly. In
      general, decreasing dynamic compliance of the tubing was not associated with
      greater inaccuracy in V(te) measurements.

PMID- 12203849
TI  - Effect of beta2-agonist treatment and spirometry on exhaled nitric oxide in
      healthy children and children with asthma.
AB  - We set out to determine the effect of spirometry and bronchodilator therapy on
      exhaled nitric oxide (FE(NO)) values in children. We hypothesized that there will
      be no difference on FE(NO) values pre- and postspirometry and following
      bronchodilator therapy. Sixteen children [(mean = 14.4 +/- 1.2 years; range, 12
      18 years; healthy controls (n = 6); asthmatics on inhaled steroids (n = 5); and
      asthmatics on no steroids (n = 5)] had exhaled nitric oxide (FE(NO)) measurements
      on 4 consecutive days as follows: pre- and postspirometry (day 1); pre- and
      postalbuterol metered dose inhaler (MDI) therapy (day 2); pre- and postspirometry
      and albuterol MDI therapy (day 3); and pre- and postspirometry and placebo MDI
      (day 4). FE(NO) was measured with a chemiluminescence analyzer, using the single
      vital capacity exhalation technique at an exhalation flow of 50 mL/sec. There
      were no statistically significant differences in FE(NO) values pre- and poststudy
      maneuvers under all experimental conditions in healthy children. However, in
      healthy children, clinically relevant (>10%) differences from baseline were
      observed on day 1 (3-18 min) and day 4 at 18 min. In children with asthma, FE(NO)
      values increased significantly by 11-19% from pretreatment levels at 8 and 18
      min, postbronchodilator on day 2, and 12-17% at 8 and 18 min post bronchodilator
      and spirometry on day 3. Spirometry and treatment with a placebo (day 4) resulted
      in a decrease in FE(NO) values by 11% at 3 min postbaseline in patients on
      inhaled steroids. The changes observed were similar in children on vs. off
      inhaled steroids, and also in well-controlled vs. poorly controlled asthma. We
      conclude that FE(NO) values should be obtained consistently either pre- and at a
      specific time postalbuterol treatment or spirometry. Alternatively, changes in
      FE(NO) values should be interpreted in relationship to the timing of these
      maneuvers.

PMID- 12203850
TI  - Sleep and breathing in Prader-Willi syndrome.
AB  - Prader-Willi syndrome (PWS) is a genetic disorder, with hypotonia being the
      predominant feature in infancy, and developmental delay, obesity, and behavioral
      problems becoming more prominent in childhood and adolescence. Children with this
      disorder frequently suffer from excessive daytime sleepiness and have a primary
      abnormality of the circadian rhythm of rapid eye movement sleep. They also have
      primary abnormal ventilatory responses to hypoxia and hypercapnia, and these
      abnormalities may be exacerbated by obesity. Children with PWS are at risk of a
      variety of abnormalities of breathing during sleep, including obstructive sleep
      apnea and sleep-related alveolar hypoventilation. Clinical evaluation should
      include a careful history of sleep-related symptoms and assessment of the upper
      airway and lung function. Polysomnography should be considered for those with
      symptoms suggestive of sleep-disordered breathing. Treatment options depend on
      the underlying problem, but may include behavioral interventions, weight control,
      adenotonsillectomy, and nocturnal ventilation.

PMID- 12203851
TI  - Pulmonary hypoplasia with an unusual prenatal history.
AB  - We describe a monochorionic, diamniotic twin with renal agenesis who received
      amniotic fluid from his normal co-twin by spontaneous rupture of the amniotic
      septum between them. By 16 weeks of gestation the presence of severe
      oligohydramnios in one twin had resulted in renal agenesis, but not in the other
      twin, who did not have oligohydramnios. By 20 weeks of gestation, the two
      amniotic fluid volumes had become the same in both twins. At 33 weeks, the twins
      were delivered by cesarean section. Despite intensive respiratory care, the twin
      with renal agenesis died from severe pneumomediastinum on day 3. At autopsy,
      pulmonary hypoplasia was demonstrated in that twin. This experiment of nature
      demonstrates that oligohydramnios during the early canalicular stage of pulmonary
      development (gestational age, 16-20 weeks) may be pathogenically important in
      pulmonary hypoplasia.

PMID- 12203852
TI  - Rhabdomyomatous dysplasia of the newborn lung associated with multiple congenital
      malformations of the heart and great vessels.
AB  - Interstitial proliferation of striated muscle in the lung is extremely rare. Most
      cases are associated with other congenital malformations, such as lung
      sequestration, diaphragmatic hernia, or cardiac malformations. We describe a
      newborn with rhabdomyomatous dysplasia of the lung associated with multiple
      congenital malformations of the heart and great vessels. The female neonate was
      born at 37 weeks of gestation as the second child to a 31-year-old woman without
      relevant previous medical or family history. In week 26 of gestation, a complex
      heart malformation and polyhydramnion were diagnosed by ultrasound. Postnatally,
      right lung hypoplasia, a bilobar right and left lung, anomalous drainage of the
      pulmonary veins, atrial and ventricular septal defects, and double-outlet right
      ventricle and multiple aortopulmonary collaterals were described. Histological
      examination of a biopsy of the right lung demonstrated the presence of numerous
      bundles of striated muscle fibers arranged randomly in the pulmonary
      interstitium. Unilateral resection of the right lung was not a therapeutic
      option, because the left lung had developed bronchopulmonary dysplasia with
      severe reduction in gas exchange as a consequence of long-term mechanical
      ventilation. Symptomatic relief and palliative cardiac surgery were offered. At
      age 5 months, the infant died of a pulmonary hemorrhage following cardiac
      surgery.

PMID- 12203853
TI  - To the editor: effect of anesthetic gases on the growth of Pseudomonas
      aeruginosa, Haemophilus influenzae, and Staphylococcus aureus.

PMID- 12203854
TI  - Detecting early structural lung damage in cystic fibrosis.
AB  - In cystic fibrosis (CF) patients, both severe lung inflammation and severe lung
      damage occur early and persist throughout life. High-resolution computed
      tomography (HRCT), a more sensitive method of detecting structural abnormalities
      than chest X-ray, shows that airways undergo substantial thickening in early CF
      lung disease. Lung function tests, which are an indirect measure of structural
      integrity, are insensitive to localized or early damage. Thickening of the
      peripheral airways causes a reduction in maximal expiratory flow at 25% of forced
      vital capacity (MEF(25)) or other measurements of peripheral air flow. Reduced
      peripheral flows, even in the presence of normal forced expired volume in 1 sec
      (FEV(1)) and forced vital capacity (FVC), should be considered an early sign of
      substantial lung damage and should stimulate aggressive treatment to prevent
      further deterioration.

PMID- 12203855
TI  - Early infection and progression of cystic fibrosis lung disease.
AB  - Chronic Pseudomonas aeruginosa infection is the major limitation in overall
      survival of patients with cystic fibrosis, and elective bronchoscopy shows that
      infection with this organism starts at a very early age. Early infection with
      nonmucoid P. aeruginosa gradually develops into chronic infection, characterized
      by the presence of microcolonies of alginate-producing (mucoid) P. aeruginosa in
      the bronchial tree. Chronic infection cannot be cured, but aggressive
      antimicrobial treatment will prolong life expectancy and decrease morbidity. It
      has, however, over the last decade become evident that early antimicrobial
      treatment of the initial infection with nonmucoid strains can prevent or at least
      postpone transition into chronic (mucoid) infection. This treatment strategy is
      likely to dramatically improve the prognosis of patients with cystic fibrosis in
      the immediate future.

PMID- 12203857
TI  - Evidence-based medicine in cystic fibrosis: how should practice change?
AB  - This critical review of current practice and research in some aspects of cystic
      fibrosis (CF) concludes that, despite recent success in prolonging life
      expectancy, there is still room for improvement in terms of earlier diagnosis and
      earlier intervention in some of its complications. Specifically, the body of
      evidence implies that neonatal diagnosis; early attention to nutrition,
      staphylococcal and pseudomonal infection, and diabetes mellitus; and early
      treatment with dornase alfa can all be expected to improve patients' quality and
      quantity of life.

PMID- 12203856
TI  - Dornase alfa in early cystic fibrosis lung disease.
AB  - Leukocytes that infiltrate cystic fibrosis (CF) sputum as a result of infection
      have long been known to liberate large amounts of DNA, which increases sputum
      viscosity and promotes the cycle of chronic lung infection and inflammation that
      ultimately leads to respiratory failure and death. It was only recently
      recognized that this vicious cycle begins in infancy, and that architectural
      damage to CF lungs is detectable even in children with normal pulmonary function
      tests. Dornase alfa cleaves DNA and improves sputum viscosity in CF. Although its
      efficacy in reducing the risk of acute infectious exacerbations and improving
      pulmonary function has been recognized for a decade, there is growing interest in
      its potential for long-term benefit in young patients with mild lung function
      abnormalities. The Pulmozyme Early Intervention Trial (PEIT) study demonstrated
      that dornase alfa reduces the risk of pulmonary exacerbations requiring i.v.
      antibiotic treatment by 34% and improves forced expiratory flow at 25-75% of
      forced vital capacity (FEF(25-75)), mid-expiratory flow at 50% of forced vital
      capacity (MEF), and forced expired volume in 1 sec (FEV(1)) over a 2-year period
      in CF patients with almost normal lung function. A post hoc subgroup analysis
      suggests that the magnitude of pulmonary function test (PFT) changes may vary,
      depending on the initial degree of lung function impairment, but that the
      reduction in exacerbations appears to be a consistent benefit. These results
      support the current view that CF patients benefit from intervention early in the
      course of their lung disease.

PMID- 12203858
TI  - Naked nuclei revisited: p63 Immunoexpression.
AB  - The presence of naked nuclei (NN) in cytological preparations of fibroadenomas is
      a well-known finding. Regardless of their importance on the differential
      diagnosis of fibroadenoma and other benign lesions of the breast, the origin of
      NN remains elusive. Despite previous efforts to characterize them, the lack of a
      reliable nuclear marker for myoepithelial cells impaired definitive conclusions.
      We performed a systematic evaluation of p63 expression in cytological and
      histological preparations of 10 fibroadenoma specimens. We observed that in
      histological sections, p63 was restricted to the nuclei of myoepithelial/basal
      cells in lobules and ducts of normal breast. In fibroadenomas, p63 decorated the
      nuclei of myoepithelial cells in the periphery of epithelial duct-like formations
      and slit-like formations. No p63 immunoreactivity was observed in stromal or
      epithelial cells. In cytological samples, almost all NN and cells surrounding
      epithelial cell clusters were stained; no stromal cell admixed with fibrillary
      matrix or epithelial cell was stained with p63. Based on our findings, we
      strongly suggest that most, if not all, NN are myoepithelial in origin.

PMID- 12203860
TI  - Distinguishing tall cell variant of papillary thyroid carcinoma from usual
      variant of papillary thyroid carcinoma in cytologic specimens.
AB  - Tall cell variant (TCV) is an aggressive form of papillary thyroid carcinoma
      (PTC), usually associated with higher local recurrence and distant metastasis.
      Some authors have suggested that TCV can be effectively diagnosed on thyroid fine
      needle aspiration (FNA); this diagnosis may help clinicians plan a more effective
      treatment regimen. The objective of this study was to compare the FNA specimens
      of TCV with those of usual variant of PTC (UV-PTC) and to define a set of
      distinguishing cytologic features. Thirty FNA specimens of histologically proven
      TCV were compared with 32 FNA specimens of histologically proven UV-PTC. All
      specimens were evaluated for the following features: papillary groups (PG),
      elongated/tall cells (EL/TC), oncocytic cytoplasm (OC), distinct cell borders
      (DCB), prominent central nucleoli (PCN), intranuclear grooves (NG), and
      intranuclear inclusions (NI). These features were semiquantitatively measured on
      a sliding scale of 0-4 in both air-dried Diff-Quik-stained and ethanol-fixed
      Papanicolaou-stained preparations. TCV showed distinctive cytologic features,
      which can distinguish them from UV-PTC. These included EL/TC, OC, and DCB and
      were also found to be statistically significant (P < 0.0001). No significant
      differences were noted for PG and NG. The NIs in TCV cases were qualitatively
      different than those in UV-PTC. In TCV there were multiple inclusions within the
      same nucleus imparting a "soap bubble appearance" to the nucleus. This feature
      was seen in almost all cases of TCV and was rarely seen in usual PTC. On the
      basis of the above-mentioned cytologic features, TCV can be distinguished from
      usual PTC in FNA specimens.

PMID- 12203859
TI  - Urine: beyond cytology for detection of malignancy.
AB  - In the present review we discuss various ancillary modalities for detection of
      malignancies in urine samples, with an emphasis on urothelial carcinomas. Flow
      cytometry, bladder tumor antigen (BTA), nuclear matrix protein (NMP), matrix
      metalloproteinase (MMP), human chorionic gonadotrophic (HCG), telomerase, and
      other techniques are discussed. DNA FCM is a relatively costly and sophisticated
      technique. It has a practical application in the diagnosis of bladder cancer
      among subjects at high risk and is of value in monitoring the course of the
      disease and anticipating recurrence following conservative treatment. The BTA
      test is a simple, rapid, and inexpensive adjunct to cystoscopy and the results of
      the test are equivalent or superior to those of voided urinary cytology. NMP-22
      immunoassay is a useful diagnostic test for predicting recurrence of urothelial
      malignancy. It is also a cost-effective and sensitive screening test for
      detecting tumor in patients with urothelial carcinoma. Beta-HCG estimation in
      urine samples appears to be an efficient diagnostic marker for the assessment of
      distant metastasis in bladder carcinoma rather than a screening test. Other
      ancillary techniques such as detection of expression of cytokeratin 20 by RT-PCR,
      MMP-9 estimation, and fluorescent in situ hybridization and telomerase activity
      are rarely applied clinically in routine urinary samples and are not cost
      effective.

PMID- 12203861
TI  - CD10 facilitates the diagnosis of metastatic renal cell carcinoma from primary
      adrenal cortical neoplasm in adrenal fine-needle aspiration.
AB  - Renal cell carcinoma (RCC) frequently metastasizes or invades the adrenal gland.
      Metastatic RCC is often difficult to differentiate from primary adrenal cortical
      neoplasm (ACN) in an adrenal fine-needle aspiration (FNA). Recently, CD10
      immunoreactivity was observed in more than 90% of RCC, but none in primary ACN.
      To facilitate the accurate diagnosis of metastatic RCC in adrenal FNA, we
      retrospectively studied the cytomorphology and CD10 immunohistochemistry in 20
      cases of FNA specimens, including 10 cases of adrenal FNA (six cases of
      metastatic RCC and four cases of primary ACN) and 10 cases of primary RCC.
      Cytomorphologically, several overlapping features were observed between primary
      ACN and metastatic RCC, including: abundant clear cytoplasm, often with
      microvesicles, large nuclei with prominent nucleoli, bare nuclei, and prominent
      vascularity. Immunostaining for CD10 was positive in 9/10 cases of primary RCC,
      5/6 cases of metastatic RCC in the adrenal gland, and 0/4 cases of primary ACN.
      Our study indicates that: 1) an accurate diagnosis of ACN in FNA specimens can
      often be difficult due to overlapping cytomorphologic features with RCC, and 2)
      CD10 immunostaining is helpful in separating metastatic RCC from a primary ACN
      and can reliably be performed on a cytologic sample.

PMID- 12203862
TI  - Long-term follow-up of women with atypical squamous cells of undetermined
      significance (ASCUS).
AB  - ASCUS is the most common epithelial abnormality diagnosed in cytology
      laboratories in the US. Recently, the clinical importance of this diagnosis has
      been seriously questioned, with some investigators advocating elimination of this
      diagnostic category. This might be inappropriate if the ASCUS designation does
      define a population that is at significant risk for the development of dysplasia.
      Cytology and surgical pathology reports for all patients diagnosed as ASCUS in
      our laboratory during 1990 were reviewed. Patients with previous dysplasia or
      carcinoma were excluded from analysis. The pathology reports for the subsequent
      9.1 yr were obtained and follow-up data collected. In 1990, 15,860 cervical
      cytology cases were examined in our laboratory. A diagnosis of ASCUS was made in
      1,117 cases (7.0%). After excluding 345 patients with previous dysplasia or human
      papillomavirus-related diagnoses and 129 patients with no follow-up specimens,
      643 study patients remained. Among these, the mean number of subsequent cervical
      smears was 4.3 (range, 1-18). Subsequent histologic material was available for
      134 (20.8%) patients and the mean number of surgical specimens was 1.5 (range, 1
      10). Squamous intraepithelial lesion (SIL) or dysplasia was subsequently
      diagnosed in 197 patients (30.6%). High-grade squamous intraepithelial lesion
      (HSIL) or at least moderate dysplasia was diagnosed in 64 patients (10.0%). In 21
      cases (3.3%) the high-grade dysplasia developed more than 2 yr after the first
      ASCUS diagnosis. Follow-up disclosed no cases of invasive carcinoma. Among ASCUS
      patients followed for up to 9 yr, 20% develop only low-grade SIL or mild
      dysplasia and 10% develop HSIL or moderate or severe dysplasia. ASCUS should be
      retained as a diagnostic category since it identifies a significant percentage of
      patients who are at an increased risk for the development of cervical dysplasia.

PMID- 12203863
TI  - Expression of NK-associated antigens in extramedullary lymph nodal blast crisis
      of chronic myeloid leukemia on fine-needle cytology.
AB  - A case is reported of a 62-yr-old male suffering from chronic myelogenous
      leukemia (CML) who developed an extramedullary, para-orthic lymph-nodal blast
      crisis without blood or bone marrow involvement and expression of CD56/NK
      associated marker. The diagnosis was performed on ultrasound-guided fine-needle
      cytology by an immunocytochemical and flow cytometric analysis. Conventional
      smears showed a monomorphous population of disperse, undifferentiated cells
      without cytoplasm. Cells showed fragile nuclei, vesicular chromatin, and evident
      nucleoli. Immunocytochemistry performed on cytospin slides were negative for
      cytokeratin, LCA, CD20, CD45Ro, and myeloperoxidase (MPO). Flow cytometry
      analysis proved the myeloid origin of the tumor by expression of CD13, CD34, and
      CD38 and showed aberrant expression of CD56. Cytological diagnosis was confirmed
      by histological examination. CD56 expression is generally an expression of NK
      lymphoid proliferation and may be observed in acute myelogenous leukemia but has
      rarely been reported in CML and its related blast crisis. This unusual
      expression, its possible explanation, the related technical problems, and
      clinicopathological aspects are discussed.

PMID- 12203864
TI  - Cytologic features of angioleiomyoma: cytologic-histologic study of 10 cases.
AB  - Fine-needle aspiration (FNA) features in 10 angioleiomyomas (ALM) were evaluated
      and correlated to histological features and clinical data. The tumors developed
      in the skin or subcutaneous tissue of the lower extremities (eight), the shoulder
      (one), and the lower arm (one). Eight tumors were painful or tender. Cytological
      specimens showed moderate or sparse cellularity. The most frequent findings were
      uniform spindle cells, seen in nine smears. In eight of these, the spindle cells
      were admixed with smooth muscle cells and fragments of collagenous tissue in
      varying proportions. The occurrence of macrophages and fat cells was less
      specific, being present in three of nine smears. One aspirate contained some
      "ganglion-like" cells and a multinucleated giant cell. Smears from ALM are not
      sufficiently characteristic to permit a histotype diagnosis, but together with
      typical clinical data (painful or tender nodule) may help to exclude other skin
      or subcutaneous lesions.

PMID- 12203865
TI  - Pilomatrixoma: clinicopathologic study of 51 cases with emphasis on cytologic
      features.
AB  - The clinical and pathologic features of 51 cases of pilomatrixoma found in our
      archives from 1990-1999 were reviewed, with emphasis on the cytopathologic
      features of the 22 cases that were sampled by fine-needle aspiration (FNA) biopsy
      prior to excision. Although uncommon, almost 20% of the pilomatrixomas in this
      series occurred in adults over age 30. Of the commonly reported features, the
      presence of basaloid cells and ghost cells in FNA smears, associated with a
      cutaneous location of the lesion, was sufficient for a confident cytologic
      diagnosis of pilomatrixoma. The presence of foreign body-type giant cells,
      nucleated squamous cells, and calcification, alone or in combination, was less
      specific, but supported a diagnosis of pilomatrixoma. Although infrequently
      reported, prominent nucleoli in basaloid cells and smears containing refractile
      keratin clumps were very useful clues in the diagnosis of pilomatrixoma. Finally,
      the routine use of cell blocks is recommended because in many of the cases
      presented ghost cells were fragmented or obscured in smears, but were more
      readily identified in cell block sections.

PMID- 12203866
TI  - Cytologic findings of myxoid neurothekeoma: case report based on fine-needle
      aspiration cytology, immunohistochemistry, and correlating histopathology.
AB  - Myxoid neurothekeomas (nerve sheath myxomas) are rare benign cutaneous neoplasms
      that may morphologically mimic other myxoid neoplasms of skin and soft tissue.
      The cytologic and histopathologic features of this lesion may resemble various
      myxoid sarcomas, chordoma, myxoid neurofibroma, dermal cutaneous mucinosis, and
      cutaneous myxoma as well as other myxoid or chondroid neoplasms. In this study, a
      myxoid neurothekeoma was analyzed using multiple techniques. We found that myxoid
      neurothekeomas reveal a nonspecific pattern by fine-needle aspiration, including
      stellate cells embedded within an abundant metachromatic myxoid stromal matrix.
      These are cytologic features shared by various other subcutaneous neoplasms and
      thus may not be helpful in forming a definitive diagnosis. Histopathologically,
      the tumor is composed of nodules of myxoid stroma containing interspersed bland
      spindled and stellate cells. Immunohistochemical studies show tumor cell
      positivity for S-100 protein and vimentin, a profile shared by other neoplasms
      with similar cytologic features and therefore of little diagnostic value. The
      histologic and cytologic differential of subcutaneous and soft tissue myxomatous
      lesions is broad and, therefore, is of unique value to the cytopathologist to
      consider myxoid neurothekeomas among the differential of other myxomatous
      neoplasms.

PMID- 12203868
TI  - Accuracy of reporting endocervical component adequacy--a continuous quality
      improvement project.
AB  - Inaccurate reporting of the absence of an endocervical (EC) component on Pap
      smears often results in slide rescreens, amended reports, clinician
      dissatisfaction, and sometimes unnecessary repeat smears. Therefore, the accuracy
      of reporting EC component adequacy was selected as a quality indicator for the
      laboratory continuous quality improvement program (CQI). The process consisted of
      problem identification, analysis of the situation, collection of data,
      implementation of solutions, and evaluation of results. The objective of the
      study was to determine if the accuracy of reporting EC component adequacy on Pap
      smears improved after application of such a program. During the first phase, 150
      Pap smears originally reported with the absence of an adequate EC component and
      150 smears reported with the presence of an adequate EC component were rescreened
      to measure the baseline accuracy of EC component adequacy reporting. The
      improvement process was then implemented. A cause-and-effect diagram was
      developed and root cause was determined. A presentation was then made to the
      cytology staff. Criteria for EC component adequacy were reviewed, examples were
      shown, and standardized marking of EC component was implemented. Following
      improvement actions, a second audit of 150 Pap smears reported with the absence
      of an adequate EC component as well as 150 smears reported with the presence of
      an adequate EC component was undertaken to measure change in performance in
      assessing EC component adequacy. For the baseline rescreening, before initiation
      of the CQI program, 98% accuracy was achieved with smears that were reported as
      adequate for EC component present. However, the accuracy with smears reported as
      absence of an adequate EC component was only 71%, i.e., an adequate EC component
      was identified in almost 1/3 of these cases on rescreen. After the implementation
      of improvement actions, the accuracy with smears reported with the presence of EC
      component remained high (98%) and the accuracy of reporting the absence of EC
      component was 90%. The difference of the latter before and after the
      implementation was statistically significant (P = 0.015, z-test). The accuracy of
      reporting EC component adequacy increased following the CQI process. Using
      reporting EC component adequacy as an example, we demonstrate that by treating
      clinical problems as quality control issues and applying basic quality
      improvement tools, a positive outcome can be effected.

PMID- 12203867
TI  - Scrape and fine-needle aspiration cytology of extraskeletal osteosarcoma.
AB  - Extraskeletal osteosarcoma is a rare malignant soft tissue tumor whose cytologic
      findings are infrequently reported. We describe scrape and fine-needle aspiration
      biopsy (FNAB) cytology findings of an extraskeletal osteosarcoma in the right
      shoulder of a 24-yr-old man. Initial computed tomography revealed multiple
      ossification foci within the lesion. After excision of the primary tumor, the
      tumor recurred 13 months later. Scrape smears of both the primary tumor and FNAB
      smears of the recurrent tumor revealed moderate cellularity, cell clusters, and
      individual cells, closely associated with dense, homogeneous, acellular matrix
      material. The cells had elongated, oval, or partially bizarre-shaped nuclei with
      a coarse chromatin pattern and prominent nucleoli. The scrape smears contained
      large fragments of matrix material consistent with osteoid.

PMID- 12203869
TI  - Conventional and liquid-based cervicovaginal cytology: a comparison study with
      clinical and histologic follow-up.
AB  - Increased rates of squamous intraepithelial lesion (SIL) diagnosis with liquid
      based cervicovaginal cytology (CVC) methods are well documented. This
      retrospective study compares the ability of the ThinPrep Pap Test (TP) and the
      conventional Pap smear (CP) to detect biopsy-proven SIL and to exclude
      nonneoplastic disease. All CVC reports from January 1999 through December 2000
      from seven community Family Medicine clinics affiliated with the University of
      Nebraska were reviewed. For women with at least one CVC diagnosis of epithelial
      cell abnormality (ECA), follow-up histology, cytology, and clinical data were
      obtained. Statistical analysis was performed using the chi-square method. SIL was
      diagnosed in 166 of 3,286 patients by TP (5.1%) and in 169 of 4,872 patients by
      CP (3.5%) (P < 0.001); 32 of the TP diagnoses (1.0%) and 34 of the CP diagnoses
      (0.7%) were high-grade SIL (HSIL). Atypical squamous or glandular cells of
      undetermined significance (ASCUS/AGUS) was the most severe abnormality diagnosed
      by TP in 218 patients (6.6%) and by CP in 279 patients (5.7%). Follow-up
      histology data on CVC SIL diagnoses showed evidence of cervical intraepithelial
      neoplasia in 94 patients screened by TP (2.9%) and in 79 patients screened by CP
      (1.6%) (P < 0.001); the biopsy diagnoses were CIN 2 or CIN 3 in 34 patients in
      the TP group (1.0%) and in 28 patients in the CP group (0.6%) (P < 0.025). Follow
      up of patients in whom the first ECA CVC diagnosis was ASCUS or AGUS disclosed a
      positive predictive value for CIN of 22.8% for TP ASCUS/AGUS diagnoses and 11.9%
      for CP ASCUS/AGUS diagnoses (P < 0.005). In this population, TP was significantly
      better than CP in detecting biopsy- proven disease and in screening out benign
      abnormalities.

PMID- 12203870
TI  - Streptococcus mitis-infected nephroblastoma. An unusual fine-needle aspiration
      diagnosis.

PMID- 12203871
TI  - Fine-needle aspiration cytology of unusual germ cell tumors of the mediastinum:
      atypical seminoma and parietal yolk sac tumor.
AB  - A 30-yr-old man presented with a mediastinal germ cell tumor that combined the
      histologic pattern of seminoma with the immunohistochemical profile of embryonal
      carcinoma (beta-HCG+/PLAP-). In FNA smears, this atypical seminoma presented as
      fragile large cells with scanty cytoplasm, vesicular nuclei, irregular and
      indistinct nucleoli, scattered singly and in loosely cohesive fragments without
      the characteristic lymphocytic or tigroid background. The cytologic features were
      more suggestive of a poorly differentiated carcinoma than seminoma, potentially
      leading to misdiagnosis and mismanagement. The second case was a 51-yr-old female
      smoker who presented with mediastinal parietal yolk sac tumor with extension to
      the lung, a rare occurrence, and contrary to the clinical impression of lung
      cancer with hilar lymph node metastasis. This case illustrates the value of using
      the unique cytologic features of parietal yolk sac tumor, i.e., the abundant,
      viscous, stringy metachromatic extracellular hyaline material associated with the
      tumor cells in reaching the accurate diagnosis.

PMID- 12203872
TI  - Prostatic adenocarcinoma metastases mimicking small cell carcinoma on fine-needle
      aspiration.
AB  - Prostate adenocarcinoma (PA) is known to metastasize widely to bone, lung, lymph
      nodes, and other sites. We have observed a rare, although distinctive,
      neuroendocrine (NE) cytomorphology of metastatic PA on fine-needle aspiration
      (FNA) that mimics small cell carcinoma (SCC). From a total of 117 cases, eight
      cases of metastatic PA diagnosed on FNA showed cytomorphologic features
      indistinguishable from SCC. All specimens were reviewed, along with
      immunoperoxidase (IPOX) studies using prostate specific (PSA, PSAP) and NE
      markers (synaptophysin, chromogranin, etc.). The patients ranged in age from 51
      68 (mean age = 63). The PSA levels at the time of FNA ranged from <0.1 to 2,892
      ng/ml (normal postprostatectomy <0.2 ng/ml). Sites of FNA included liver (two),
      soft tissue (five), and lymph node (one). FNA was performed from 11 mo to 6 yr
      after the initial diagnosis of the primary tumor. All primary PA were of high
      Gleason grade ranging from 7-9. None of the primary PA showed neuroendocrine
      morphology. Cytomorphologic characteristics observed on FNA included
      predominantly single cells with occasional sheets or loose cell aggregates. A
      predominant NE nuclear morphology was evident (i.e., hyperchromasia, fine dusty
      chromatin, inconspicuous nucleoli, nuclear molding, chromatinic crush artifact,
      karyorrhexis, mitoses, etc.), with none of the tumors displaying glandular
      formation. Taken together, these features gave these metastases a cytomorphology
      indistinguishable from SCC. IPOX studies revealed PSA-positivity (5/7), PSAP
      positivity (4/7), and only focal NE markers positivity (3/6). Metastatic prostate
      carcinoma may rarely mimic a SCC (6.8% in this study). This often necessitates
      further patient workup to identify the primary source for the patient's
      metastasis, particularly if the patient has multiple lesions. An accurate
      diagnosis of these lesions as PA metastases is essential for effective, timely
      treatment and therapeutic design.

PMID- 12203873
TI  - Diagnostic significance of endocervical glandular cells with "golden-yellow"
      mucin on pap smear.
AB  - Endocervical glandular cells rarely show "golden-yellow" mucin staining using the
      Papanicolaou technique, whereas the cells of adenoma malignum (minimal deviation
      adenocarcinoma) do. To further evaluate the significance of this finding, we
      reviewed the Pap smears of six cases in which atypical glandular cells containing
      golden-yellow mucin was identified. Microscopic examination of the hysterectomy
      specimens confirmed one case of adenoma malignum, whereas the other five cases
      were diagnosed as endocervical glandular hyperplasia with pyloric gland
      metaplasia. Glandular cells observed in all six cases were filled with golden
      yellow mucin. In the case of adenoma malignum the nuclei were somewhat more
      enlarged and the chromatin texture was coarsely granular, although a distinction
      between adenoma malignum and the five benign lesions was difficult. Special
      staining performed on tissue sections in all cases demonstrated that the
      intracytoplasmic mucin of the glandular cells in portion of both pyloric gland
      metaplasia and adenoma malignum was predominantly PAS-positive and showed
      immunoreactivity for M-GGMC-1 (HIK1083), which reacts with pyloric gland mucin of
      the stomach. A review of 1,165 consecutive Pap smears failed to identify cells
      with golden-yellow mucin. These observations indicate that golden-yellow mucin on
      Papanicolaou smear seems to represent a gastric phenotype of endocervical
      glandular cells, which is a unique characteristic shared by adenoma malignum and
      pyloric gland metaplasia. This finding should therefore be regarded as a warning
      sign, raising the possibility of adenoma malignum and requiring prompt
      histopathologic assessment, although not of itself diagnostic of malignancy.

PMID- 12203874
TI  - Fine-needle aspiration biopsy of the retroperitoneum: a series of 111 cases not
      including specific organs.
AB  - We report on our experience in fine-needle aspiration (FNA) biopsy of the
      retroperitoneum: 111 FNA biopsies performed on 99 patients. Cytologic diagnoses
      were divided into four groups: nondiagnostic (unsatisfactory samples because of a
      low cellularity and/or improperly prepared smears) aspirates (20%), benign (16%),
      suspicious for malignancy (13%), and malignant (50%). There were no known false
      positive samples. We had two false-negative diagnoses due to sampling errors.
      Among diagnostic smears, the procedure showed a sensitivity of 97% and a
      specificity of 100%. The predictive value of a positive result was 100% and the
      predictive value of a negative result was 90%. The overall accuracy was 98%.
      Metastatic carcinomas accounted for the largest number of lesions in the group of
      malignant tumors. A primary tumor site was known for the majority of the cases
      before the aspiration was performed. In the remaining cases we were unable to
      suggest an origin. It is therefore important to emphasize the role of ancillary
      studies in patients that are at the first assessment of the disease or when a
      second intercurrent malignancy is suspected. In our limited experience, a
      suggestion of the correct subtype of retroperitoneal sarcoma was not possible. As
      in the rest of cytopathology, a multidisciplinary approach is mandatory in this
      setting to improve patient management.

PMID- 12203875
TI  - Application of molecular genetics to the diagnosis of lymphoid-rich effusions:
      study of 95 cases with concomitant immunophenotyping.
AB  - The cytological differentiation between reactive lymphocytosis and malignant
      lymphoma in serous effusions is often difficult. The present study was designed
      to evaluate the potential contribution of molecular genetic clonality analysis to
      a solution to this problem. We examined the cytological specimens of 95
      consecutive patients collected during a 4-yr period, including 74 pleural, 20
      peritoneal, and one pericardial fluids. Cytological diagnosis in the 95
      lymphocyte-rich effusions was positive for lymphoma in 20 cases, suspicious for
      lymphoma in 26 cases, and negative in 49 cases. The analysis by ICC was not
      carried out, inconclusive, or noninterpretable in 25 cases. In five cases
      molecular genetic analysis was hampered by technical problems. By
      immunocytochemistry, eight additional cases of lymphoma were detected and lineage
      classification was achieved in 15 of the 20 cytologically positive effusions. PCR
      and Southern blot analysis were used to assess B- and T-cell clonality.
      Monoclonality was found in 40 (42%) of the 95 effusions analyzed. One-third of
      the effusions with a monoclonal B-cell gene rearrangement were detected by
      Southern blot analysis but not by the PCR performed in parallel. The results of
      molecular genetic analysis were corroborated by histological findings and/or
      clinical evolution in 15 cases. Our results indicate that molecular genetic
      analysis is a useful tool in the analysis of lymphocyte-rich serous effusions.

PMID- 12203876
TI  - Cytohistologic correlations in 56 synovial sarcomas in 36 patients: the Institut
      Curie experience.
AB  - Synovial sarcoma (SS) is a high-grade malignant soft tissue tumor that manifests
      different phenotypic subtypes that may render their cytologic evaluation
      challenging. Although several cytologic studies of SS have been published,
      correlative studies of cytologic and corresponding histologic features are
      limited. To better define the cytological features of various SS forms, we
      reviewed the cytologic and the corresponding histologic material of 56 tumors
      from 36 patients. Classical patterns were defined as dispersed or small clusters
      of cells with bland chromatin, inconspicuous nucleoli, oval to spindle-shaped
      cytoplasm and branching tumor tissue fragments, vessel stalks, acinar structures
      in scant mucin background, seen in all 53 (94.7%) cellular cases. Epithelial,
      squamous, round cells, mast cells, necrosis, comma-like nuclei, marked nuclear
      atypia, secretory mucin, and rosette-like structures were also occasionally
      observed. Comparing the histological subtype we noted that epithelial cells and
      secretory mucin were restricted to biphasic SS, round cells to poorly
      differentiated SS, and comma-like nuclei to monophasic fibrous SS. We conclude
      that the classical pattern is highly suggestive of SS of all three monophasic,
      biphasic, or poorly differentiated subtypes. These characteristics, along with
      molecular genetic studies, may improve the cytologic diagnosis of SS.

PMID- 12203877
TI  - Cytohistologic correlations of 24 malignant peripheral nerve sheath tumor (MPNST)
      in 17 patients: the Institut Curie experience.
AB  - Cytomorphological patterns of malignant peripheral nerve sheath tumor (MPNST) are
      insufficiently documented in the literature. Cytological and histological
      specimens in 24 tumors in 17 patients were correlated. The review of the original
      cytology reports showed that four (16.6%) tumors were correctly diagnosed, eight
      (33.3%) were diagnosed as sarcoma not otherwise specified, four (16.7%) as
      fibrosarcoma, three (12.5%) as synovial sarcoma, three (12.5%) as leiomyosarcoma,
      and one (4.2%) case each as malignant fibrous histiocytoma and rhabdomyosarcoma.
      At the review tumors were histologically reclassified as well-differentiated
      MPNST in 11 (45.9%) cases, anaplastic MPNST in 11 (45.9%) cases, and epithelioid
      MPNST and malignant Triton tumor in one (4.2%) case each. Cytologically, well
      differentiated MPNST were composed of polymorphous oval to round cells, small
      spindle-shaped cells with wavy and comma-like naked nuclei, and a fibrillary,
      delicate stroma. Anaplastic MPNST, moreover, were composed of anaplastic giant
      and polymorphous cells. The malignant Triton tumor was composed of oval to round
      rhabdomyoblastic cells with eccentric nuclei and the epithelioid MPNST of
      polymorphous and round, epithelial-like cells. The cytological diagnosis of MPNST
      may be difficult, especially in anaplastic tumors. The correlation between the
      cytological features and the clinical information--origin of the tumor from a
      nerve trunk, a preexisting neurofibroma, patients with known history of
      neurofibromatosis 1--could be indicative of an MPNST diagnosis.

PMID- 12203878
TI  - Leukoerythrophagocytosis by sinus histiocytes: case report.
AB  - Leukoerythrophagocytosis by sinus histiocytes in the lymph nodes is a rare
      cytological observation. Though often seen in lymph nodes draining malignancies,
      one may occasionally encounter them in vascular lesions. We report a case of
      leukoerythrophagocytosis by sinus histiocytes of the right supraclavicular lymph
      nodes in a 35-yr-old male. He presented with a painful soft tissue mass in the
      right anterior region of the chest wall extending into the axilla of 6 mo
      duration. Bilateral radial pulsations were absent. The patient had received
      treatment for pulmonary tuberculosis 1 yr ago. FNAC of the soft tissue mass
      revealed only blood. Radiological evaluation revealed a vascular lesion, with
      smooth borders, extending into the upper zone of right lung and displacing the
      second rib inferiorly. Doppler evaluation confirmed it to be a right subclavian
      aneurysm with arteritis.

PMID- 12203879
TI  - Maxillary odontogenic myxoma: a diagnostic pitfall on aspiration cytology.
AB  - A painless, slow-growing cheek swelling in a young male clinically considered a
      salivary gland mass was aspirated. Cytology smears were hypocellular. The
      striking feature was abundant myxoid material with a few monomorphic oval cells,
      interpreted as myxoid variant of pleomorphic adenoma. Subsequent CT scan was
      suggestive of a malignant tumor but biopsy confirmed it as myxoma. Myxoma of the
      jaw is a rare benign tumor that has a tendency for bone destruction, invasion
      into surrounding structures, and a relatively high recurrence rate. Maxillary
      myxoma is less frequent but behaves more aggressively than in the mandible, as it
      spreads through the maxillary sinus. Cytologically, it should be differentiated
      from other tumors showing predominant myxoid change. Awareness of potential
      diagnostic pitfalls and careful evaluation of clinical and radiological data is
      necessary to narrow the differential diagnosis.

PMID- 12203880
TI  - Cytologic features of alveolar soft part sarcoma: report of three cases.
AB  - Alveolar soft part sarcoma (ASPS) is a rare, high-grade, epithelial-like sarcoma
      that shows characteristic histopathologic findings. Although a chromosomal
      anomaly that seems specific has been recently described, its diagnosis is based
      on histologic and ultrastructural features. The tumor shows no specific
      immunohistologic findings. Cytologic features of three cases of ASPS are
      presented. Preoperative fine-needle aspiration (FNA) of the primary soft tissue
      tumor was performed in two cases. In another two, mediastinal and pulmonary and
      subcutaneous metastatic lesions were aspirated. In all cases the cytologic image
      was identical with numerous, dissociated, large neoplastic cells with round-to
      plasmocytoid morphology. Cytoplasmic fragility and granularity with abundant,
      atypical, naked nuclei were present. In one case, FNA material was available for
      ultrastructural studies. It disclosed the characteristic cytoplasmic crystalline
      structures. A specific cytologic diagnosis of ASPS was given in all cases. In
      conclusion, ASPS is a rare neoplastic entity that shows a characteristic
      cytologic image. When accompanied by an adequate clinical context it permits
      specific preoperative recognition. While immunocytologic studies are helpful to
      exclude other neoplasms, ultrastructure may result in an exact diagnosis.

PMID- 12203881
TI  - Integrating fine-needle aspiration into a daily practice involving thyroid
      disorders: the Washington Hospital Center approach.

PMID- 12203883
TI  - Interinstitutional review of thyroid fine-needle aspirations.

PMID- 12203882
TI  - Nonneoplastic findings in loop electrical excision procedure specimens from
      patients with persistent atypical squamous cells of uncertain significance in two
      consecutive pap smears.
AB  - The present study aimed to determine the histopathological correspondence of the
      diagnosis of atypical squamous cells of uncertain significance (ASCUS) in the
      absence of squamous intraepithelial neoplasia (SIL) in loop electrical excision
      procedure (LEEP) products. Retrospective histopathological analysis of 70 LEEP
      products preceded by ASCUS was consistently detected by two consecutive Pap
      smears. The presence or absence of several histopathological findings in cases
      with (23/70) and without (47/70) histological diagnosis of SIL were compared.
      Immature squamous metaplasia, severe cervicitis, and tube-endometrial metaplasia
      were found with similar frequency on positive and negative neoplastic disease
      specimens. Reactive squamous atypia, keratosis, atrophy, glandular
      reactive/inflammatory atypia, tunnel clusters, and microglandular hyperplasia
      were less frequently found in LEEP specimens presenting with SIL. Reactive
      squamous atypia and keratosis were consistently associated with SIL absence and
      appear to be responsible for the cytological diagnosis of ASCUS (P < 0.05).

PMID- 12203885
TI  - Pseudopodia-like cytoplasmic projections in melanoma cells.

PMID- 12203886
TI  - Effects of Taxol on ascites cytology from a patient with fallopian tube
      carcinoma: report of a case with ultrastructural studies.

PMID- 12203890
TI  - Proteome analysis of differentially displayed proteins as a tool for
      investigating ozone stress in rice (Oryza sativa L.) seedlings.
AB  - Employing classical two-dimensional electrophoresis (2-DE), amino acid sequencing
      and immunoblot analysis, we examine for the first time the effect of ozone, a
      highly notorious environmental pollutant, on rice seedling proteins. Drastic
      visible necrotic damage to leaf by ozone and consequent increase in ascorbate
      peroxidase protein(s) was accompanied by rapid changes in the 2-DE protein
      profiles, over controls. Out of a total of 56 proteins investigated, which were
      reproducible in repeated experiments, 52 protein spots were visually identified
      as differentially expressed over controls. Six proteins were N-terminally
      blocked, and the sequence of 14 proteins could not be determined, whereas 36
      proteins were N-terminally and one was internally sequenced. Ozone caused drastic
      reductions in the major leaf photosynthetic proteins, including the abundantly
      present ribulose-1, 5-bisphosphate carboxylase/oxygenase, and induction of
      various defense/stress related proteins. Most prominent change in leaves, within
      24 h post-treatment with ozone, was the induced accumulation of a pathogenesis
      related (PR) class 5 protein, three PR 10 class proteins, ascorbate
      peroxidase(s), superoxide dismutase, calcium-binding protein, calreticulin, a
      novel ATP-dependent CLP protease, and an unknown protein. Present results
      demonstrate the highly damaging effect of ozone on rice seedlings at the level of
      the proteome.

PMID- 12203891
TI  - Analytical and biological variances associated with proteomic studies of Medicago
      truncatula by two-dimensional polyacrylamide gel electrophoresis.
AB  - Two-dimensional polyacrylamide gel electrophoresis (2-DE) and mass spectrometry
      are being used as proteomic tools in an integrated functional genomics program
      focused on the model legume Medicago truncatula. Due to the perceived high levels
      of indeterminate error associated with 2-DE we deemed it necessary to quantify
      the coefficient of variance (or relative standard deviation) for both analytical
      and biological sources associated with 2-DE of Medicago truncatula leaf protein
      extracts. Leaf protein extracts were chosen because of their biological
      significance and due to the more challenging nature of green tissues. Analytical
      variance was calculated for fifty proteins from ten replicate 2-DE gels of the
      same protein extract. Biological variance was calculated for the same fifty
      proteins from ten independent 2-DE gel analyses of ten independent but similar
      plants grown under identical conditions. Average analytical and biological
      variances were calculated for both data sets and represent the average variance
      of approximately 500 independent measurements of protein concentration.
      Analytical variance was determined to be 16.2% and biological variance was
      determined to be 24.2%. These average variances provide a quantified and
      statistical basis for evaluation of protein expression changes in future
      comparative proteomic investigations. It is proposed that 2-DE measured protein
      expression levels should differ by a minimum of 3.92sigma (i.e. /+/-2sigma/ and
      sigma = standard deviation), or 94.7% based on our measured variances, for the
      difference to be significant at the 95% confidence level.

PMID- 12203892
TI  - High throughput two-dimensional blue-native electrophoresis: a tool for
      functional proteomics of mitochondria and signaling complexes.
AB  - The recent upsurge in proteomics research has been facilitated largely by
      streamlining of two-dimensional (2-D) gel technology and the parallel development
      of facile mass spectrometry for analysis of peptides and proteins. However,
      application of these technologies to the mitochondrial proteome has been limited
      due to the considerable complement of hydrophobic membrane proteins in
      mitochondria, which precipitate during first dimension isoelectric focusing of
      standard 2-D gels. In addition, functional information regarding protein:protein
      interactions is lost during 2-D gel separation due to denaturing conditions in
      both gel dimensions. To resolve these issues, 2-D blue-native gel electrophoresis
      was applied to the mitochondrial proteome. In this technique, membrane protein
      complexes such as those of the respiratory chain are solubilized and resolved in
      native form in the first dimension. A second dimension sodium dodecyl sulfate
      polyacrylamide gel electrophoresis gel then denatures the complexes and resolves
      them into their component subunits. Refinements to this technique have yielded
      the levels of throughput and reproducibility required for proteomics. By coupling
      to tryptic peptide fingerprinting using matrix-assisted laser
      desorption/ionization-time of flight mass spectrometry, a partial mitochondrial
      proteome map has been assembled. Applications of this functional mitochondrial
      proteomics method are discussed.

PMID- 12203893
TI  - Proteomic analysis of human biopsy samples by single two-dimensional
      electrophoresis: Coomassie, silver, mass spectrometry, and Western blotting.
AB  - Proteomic analysis of myocardial tissue from patient populations is critical to
      our understanding of cardiac disease, but has been limited until now by the small
      size of biopsies (approximately 20-50 microg), and complicated by the difference
      in relative abundance of contractile proteins over other cellular components.
      Here we describe an approach to analysis of myocardial biopsies from patients
      undergoing coronary artery bypass surgery. First, individual biopsies are
      selectively extracted, producing subfractions that correspond to the contractile
      proteins and the cytosolic proteins. Two-dimensional electrophoresis separated
      proteins are detected by first staining with Coomassie blue then silver, to
      permit a wider range of accurate quantification. Western blotting of two
      dimensional separated samples, to validate peptide mass fingerprinting data,
      previously required additional gel separations for transfer since staining
      protocols are not compatible with transfer to membranes or immunoblotting. An
      existing silver destaining protocol was adapted to allow removal of silver from a
      whole gel, followed by transfer and Western blotting. An existing Coomassie blue
      removal protocol was also adapted to permit Western blotting of gels stained with
      Coomassie blue and silver. Together, these techniques permit peptide mass
      fingerprinting concurrent with Western blotting of a single protein spot from a
      single biopsy, eliminating the need for repeated gel separations, and improving
      spot alignment between immunoblots and stained gels. In the end, this approach
      may allow a more complete characterization of protein changes in small human
      biopsies, and also reduce the number of repeated gel separations necessary for a
      standard proteomic analysis.

PMID- 12203894
TI  - Two-dimensional analysis of myocardial protein expression following myocardial
      ischemia and reperfusion in rabbits.
AB  - Myocardial ischemia and reperfusion injury (MI/R) can be related to leukocyte
      activation with subsequent release of cytokines and oxygen derived free radicals.
      Activation of the complement system has been implicated in the pathogenesis of
      myocardial ischemia and reperfusion injury. Inflammatory injury will subsequently
      result in cellular activation and protein synthesis. In the present study we
      analyzed the myocardial protein expression and its pattern following myocardial
      ischemia and reperfusion, with and without complement inhibition with the
      synthetic serine protease inhibitor Futhan/nafamstat mesilate (FUT-175) known to
      inhibit classical and alternative complement pathway in a rabbit model of
      myocardial ischemia and reperfusion (60 min I+180 min R). FUT-175 significantly
      reduced myocardial necrosis, i.e. creatine kinase release which were analyzed for
      the three groups (p<0.05). Similarly, histological analysis demonstrated
      preservation of myocardial tissue injury and reduced leukocyte accumulation
      following FUT-175 treatment. Further, the myocardial protein expression was
      analyzed by two-dimensional gel electrophoresis following MI/R in the different
      groups. The protein patterns were evaluated by means of MELANIE III, a computer
      assisted gel analysis system. The biochemical identification of the proteins of
      interest was, achieved using nanohigh-performance liquid
      chromatography/electrospray ionization-tandem mass spectrometry. On average, 509
      +/- 25 protein spots were found on the gels. A pattern of 480 spots with
      identical positions was found on every gel of five animals of each group. We
      analyzed ten spots which were significantly altered (i.e., in eight spots we
      observed decreased protein expression and in two spots we observed increased
      expression, vehicle vs. sham), by using mass spectrometry. Superoxide dismutase
      precursor and alphaB-crystallin were identified. We compared sham group vs.
      vehicle group and vehicle group vs. FUT-175 treated animals. Expression of the
      two identified proteins decreased by half the amount in the vehicle group when
      compared to sham treated animals. Treatment with FUT-175 preserved significantly
      superoxide dismutase precursor and alphaB-crystallin protein expression when
      compared to vehicle animals. The results present marked differences in myocardial
      protein expression after ischemia and reperfusion and following treatment with
      the complement inhibitor FUT-175. Our results illustrate the application of
      proteomics to discover possible new therapeutic targets or to detect unexpected
      effects of pharmacological inhibitors.

PMID- 12203895
TI  - Prediction of translocation and cleavage of heterogeneous ribonuclear proteins
      and Rho guanine nucleotide dissociation inhibitor 2 during apoptosis by
      subcellular proteome analysis.
AB  - Jurkat T cells induced to undergo apoptosis by the CD95(Fas/Apo-1) pathway were
      investigated by proteome analysis. The most prominent differing protein spots of
      apoptotic and nonapoptotic cells were identified as various heterogeneous
      ribonuclear proteins (hnRNPs) and Rho guanin nucleotide dissociation inhibitor
      (GDI) 2. In apoptotic cells, four spots slightly differing in molecular mass
      and/or isoelectric point were identified as Rho GDI 2 with the mass and pI as
      expected after caspase-3 cleavage near the N-terminus. Subcellular proteome
      analysis revealed that Rho GDI 2 was highly enriched in the cytosolic fraction,
      present in minor amounts in the nuclear fraction and absent from the
      mitochondrial fraction. In apoptotic cells however, the spots representing
      processed and modified Rho GDI 2 were found in the cytosol, in the nucleus and
      also the mitochondria at different spot positions. In addition, twelve different
      hnRNPs were identified to be altered after induction of cell death of which
      hnRNPs A/B, D, F, H, I and L were hitherto unknown to be modified during
      apoptosis. Most of the hnRNP spots were found in the nucleus of nonapoptotic
      cells, whereas these proteins, either modified or unmodified, relocated to the
      cytosol and/or the mitochondria in apoptotic cells. Our results demonstrate that
      modification of proteins during apoptosis is often accompanied by their
      relocalisation between cellular compartments.

PMID- 12203896
TI  - A proteomic approach to identify developmentally regulated proteins in Leishmania
      infantum.
AB  - We used comparative two-dimensional gel electrophoresis (2-DE) and mass
      spectrometry methodologies to highlight and identify proteins that are
      differentially expressed in the intracellular stage of the parasite Leishmania
      donovani infantum, a causative agent of visceral leishmaniasis. During its
      digenetic life cycle, Leishmania alternates between the alimentary tract of the
      sandfly vector as an extracellular promastigote and the acidic phagolysosomes of
      macrophage cells as an intracellular amastigote. Proteins differentially
      expressed in the intracellular form of the parasite are thought to be important
      for intracellular survival and pathogenesis. We used narrow pH range strips for
      isoelectric focusing to resolve soluble proteins of both developmental stages of
      L. infantum. More than 62 proteins differentially expressed in amastigotes were
      detected among approximately 2000 protein spots resolved by 2-DE. A quadrupole
      time-of-flight analysis of few selected protein spots, specifically expressed in
      the amastigote stage, permitted the identification of two proteins, part of the
      energetic metabolism pathways, the isocitrate dehydrogenase and the glycolytic
      enzyme triosephosphate isomerase. The kinetic parameters of these two enzymes
      were measured in both developmental stages of the parasite and their activity was
      indeed found to be higher in amastigotes. These findings bring a new insight in
      our understanding of metabolic and energy requirements of the intracellular form
      of Leishmania. Comparative analysis of the proteome of both developmental stages
      of the protozoan parasite Leishmania should permit the identification of protein
      candidates for the development of vaccines and new drugs.

PMID- 12203897
TI  - Alterations of stress related proteins in genetically altered mice revealed by
      two-dimensional differential in-gel electrophoresis analysis.
AB  - Transgenic, knockout and knockin mice are useful tools for linking specific genes
      with behaviour and other complex biological processes. However, complications
      arising due to compensatory changes, genetic background differences and other
      factors could lead to difficulty in interpreting the resulting changes in
      phenotype. We have used fluorescence two-dimensional differential in-gel
      electrophoresis in combination with matrix-assisted laser desorption/ionization
      time of flight mass fingerprinting to investigate the possibility that distinct
      genetic alterations can lead to common protein expression changes in genetically
      modified mice. Brain proteomes were compared from two transgenic mouse strains
      (Tg2576 x TgPS1 and Tg2576), two knockout mouse strains (5-HT(7)R -/- and
      GABA(A)Ralpha5 -/-) and one knockin mouse strain (GABA(A)Ralpha1-H101R). Both of
      the transgenic models showed an isoform change in the heat shock 70 related
      protein, mortalin. The knockout and knockin models showed similar changes in
      mortalin expression along with an alteration of the anti-oxidant protein 2. The
      observed proteomic alterations indicate that stress-responsive protein pathways
      may be altered artefactually in all of the mouse models used in this study and
      highlights an area where caution is needed in interpreting proteomic changes in
      genetically modified mice.

PMID- 12203898
TI  - Proteomic analysis of human lysosomes: application to monocytic and breast cancer
      cells.
AB  - To date, about fifty lysosomal hydrolases have been identified, and most of them
      are targeted towards the lysosomes through a specific mannose-6-phosphate (M-6-P)
      tag. As more lysosomal hydrolases were expected to be discovered, we performed a
      proteomic study of soluble lysosomal proteins. Human cells were induced to
      secrete M-6-P proteins which were affinity purified on immobilized M-6-P
      receptor. The purified proteins were resolved by two-dimensional electrophoresis
      and analyzed by mass spectrometry. Twenty-two proteins were identified, among
      which 16 were well-known lysosomal hydrolases. The remaining species distributed
      as follows: epididymis-specific alpha-mannosidase is a new mannosidase homolog,
      cystatin F and CREG (cellular repressor of E1A-stimulated genes) were previously
      identified as M-6-P proteins (Journet et al., Electrophoresis 2000, 21, 3411
      3419), and the last three, which are not hydrolases, were up to now considered as
      nonlysosomal. This two-dimensional reference map of human U937 M-6-P proteins was
      afterwards used for comparison with M-6-P proteins purified either from U937
      differentiated into macrophage-like cells, or from human breast cancer MCF7
      cells. Phorbol ester induced differentiation of U937 cells led to limited
      proteolytic cleavage or maturation of a discrete number of hydrolases. Five
      additional lysosomal hydrolases were identified from MCF7 samples. These results
      prove the usefulness of such a procedure to analyze the lysosomal content of
      various cell lines, to discover new M-6-P proteins, as well as to point towards
      unknown biological processes.

PMID- 12203899
TI  - Proteome analysis of a Lactococcus lactis strain overexpressing gapA suggests
      that the gene product is an auxiliary glyceraldehyde 3-phosphate dehydrogenase.
AB  - The sequence of the genome from the Lactococcus lactis subspecies lactis strain
      IL1403 shows the presence of two reading frames, gapA and gapB, putatively
      encoding glyceraldehyde 3-phosphate dehydrogenase (GAPDH). Previous proteomic
      analysis of the L. lactis subspecies cremoris strain MG1363 has revealed two
      neighbouring protein spots, GapBI and GapBII, with amino terminal sequences
      identical to the product of gapA from the L. lactis subspecies cremoris strain
      LM0230 and that of the two IL1403 sequences. In order to assign the two protein
      spots to their respective genes we constructed an L. lactis strain that
      overexpessed the gapA gene derived from MG1363 upon nisin induction. Compared to
      the wild-type, the overexpressing strain had a 3.4-fold elevated level of
      specific GAPDH activity when grown in the presence of nisin. In both MG1363 and
      the gapA overexpressing strain the GAPDH activity was specific for NAD. No NADP
      dependent activity was detected. Proteome analysis of the gapA overexpressing
      strain revealed two new protein spots, GapAI and GapAII, not previously detected
      in proteome analysis of MG1363. Results from mass spectrometry analysis of GapA
      and GapB and comparison with the deduced protein sequences for the GAPDH isozymes
      from the genome sequence of strain IL1403 allowed us to assign GapA and GapB to
      their apparent IL1403 homologues encoded by gapA and gapB, respectively.
      Furthermore, we suggest that a homologue of a gapB product, represented by GapB,
      is the main source of GAPDH activity in L. lactis during normal growth.

PMID- 12203900
TI  - Global analysis of the Brucella melitensis proteome: Identification of proteins
      expressed in laboratory-grown culture.
AB  - Brucella melitensis is a facultative intracellular bacterial pathogen that causes
      brucellosis, a zoonotic disease primarily infecting sheep and goats,
      characterized by undulant fever, arthritic pain and other neurological disorders
      in humans. A comprehensive proteomic study of strain 16M was conducted to
      identify and characterize the proteins expressed in laboratory-grown culture.
      Using overlapping narrow range immobilized pH gradient strips for two-dimensional
      gel electrophoresis, 883 protein spots were detected between pH 3.5 and 11. The
      average isoelectric point and molecular weight values of the detected spots were
      5.22 and 46.5 kDa, respectively. Of the 883 observed protein spots, 440 have been
      identified by matrix-assisted laser desorption/ionization-mass spectrometry.
      These proteins represent 187 discrete open reading frames (ORFs) or 6% of the
      predicted 3197 ORFs contained in the genome. The corresponding ORFs of the
      identified proteins are distributed evenly between each of the two circular B.
      melitensis chromosomes, indicating that both replicons are functionally active.
      The presented proteome map lists those protein spots identified to date in this
      study. This map may serve as a baseline reference for future proteomic studies
      aimed at the definition of biochemical pathways associated with stress responses,
      host specificity, pathogenicity and virulence. It will also assist in
      characterization of global proteomic effects in gene-knockout mutants.
      Ultimately, it may aid in our overall understanding of the cell biology of B.
      melitensis, an important bacterial pathogen.

PMID- 12203901
TI  - Increased protein entry together with improved focussing using a combined
      IPGphor/Multiphor approach.

PMID- 12203904
TI  - The use of hydrophilic groups in aqueous organic reactions.
AB  - The representative examples of beneficial effects of hydrophilic groups in
      aqueous organic reactions are described, including the Diels-Alder reactions,
      hetero Diels-Alder reactions, Claisen rearrangement, radical reactions, and
      transition metal-catalyzed reactions. Although the low solubility of organic
      molecules in water has been a bane in aqueous organic reactions, the
      incorporation of hydrophilic groups into the substrate structure can overcome the
      solubility problem and at the same time enhance the hydrophobic effect. In some
      cases, interesting micellar effects are observed because of the amphiphilic
      natures of such molecules. The emerging concept of "removable hydrophilic group,"
      in which the solubility problems have been alleviated, yet the initial product
      can still be transformed into a variety of products with the removal of the
      hydrophilic groups, is also described.

PMID- 12203905
TI  - Properties of some alkyl substituted phthalocyanines and related macrocycles.
AB  - This report provides an account of research undertaken at the University of East
      Anglia, United Kingdom, into phthalocyanine derivatives substituted at six or
      more of the nonperipheral sites by alkyl groups. When first prepared they were
      only the second series of substituted phthalocyanines known to exhibit columnar
      liquid crystal behaviour. The compounds also form structured films by the spin
      coating technique, a formulation with potential for FET devices. The zinc
      metallated derivatives are photosensitisers of singlet oxygen and show good
      potential for applications in photodynamic therapy. A mixed cyclotetramerisation
      of a 3,6-dialkylphthalonitrile with a second aromatic dinitrile forms so-called 3
      : 1 phthalocyanines in which three of the benzenoid rings are substituted with
      two alkyl groups and the fourth is substituted differently. Appropriate
      substituents provide amphiphilic compounds that form well-ordered films by the
      Langmuir-Blodgett method and self-assembly techniques. Characterisation of the
      films using a variety of methods is discussed and applications described.
      Examples of 3 : 1 phthalocyanine-like macrocycles in which one of the benzenoid
      rings is replaced by a heterocycle extend the range of properties exhibited.
      These include broadband absorption in the near infrared and, in particular cases,
      edge-to-face dimerisation through coordination of a pyridine nitrogen to a zinc
      centre in a second macrocycle. The potential for using suitably functionalised 3
      : 1 phthalocyanines as building blocks for more complex structures such as liquid
      crystalline main-chain polymeric phthalocyanines and phthalocyanino
      dehydroannulenes is described.

PMID- 12203906
TI  - A new concept: the use of vanadium complexes in the treatment of diabetes
      mellitus.
AB  - In the 21st century, patients suffering from diabetes mellitus (DM), a lifestyle
      related disease, will increase more than in the 20th century. DM is threatening
      because of the development of many severe secondary complications, including
      atherosclerosis, microangiopathy, renal dysfunction and failure, cardiac
      abnormalities, diabetic retinopathy, and ocular disorders. Generally, DM is
      classified as either insulin-dependent type 1 or noninsulin-dependent type 2 DM.
      Type 1 DM is treated only by daily insulin injections; type 2 DM is treated by
      several types of synthetic therapeutic substances together with a controlled diet
      and physical exercise. Even with these measures, the daily necessity for several
      insulin injections can be painful both physically and mentally, whereas the
      synthetic therapeutic substances used over the long term often have side effects.
      For those reasons, the creation and development of a new class of pharmaceuticals
      for treatment of DM in the 21st century would be extremely desirable. In the last
      half of the 20th century, investigations of the relationships among diseases and
      micronutrients, such as iron, copper, zinc, and selenium, have been numerous.
      Research into the development of metallopharmaceuticals involving the platinum
      containing anticancer drug, cisplatin, and the gold-containing rheumatoid
      arthritis drug, auranofin, has also been widespread. Such important findings
      prompted us to develop therapeutic reagents based on a new concept to replace
      either insulin injections or the use of synthetic drugs. After many trials, we
      noticed that vanadium might be very useful in the treatment of DM. Before the
      discovery of insulin by Banting and Best in 1921 and its clinical trial for
      treating DM, the findings in 1899, in which orally administered sodium vanadate
      (NaVO(3)) was reported to improve human DM, gave us the idea to use vanadium to
      treat DM. However, it has taken a long time to obtain a scientific explanation as
      to why the metal ion exhibits insulin-mimetic or blood-glucose lowering effects
      in in vitro and in vivo experiments. After investigations from many perspectives
      involving biochemistry and bioinorganic chemistry, vanadyl sulfate (VOSO(4)) and
      its complexes with several types of ligands have been proposed as useful for
      treating DM in experimental diabetic animals. On the basis of a mechanistic
      study, this article reports on recent progress regarding the development of
      antidiabetic vanadyl complexes, emphasizing that the vanadyl ion and its
      complexes are effective not only in treating or relieving both types of DM but
      also in preventing the onset of DM.

PMID- 12203907
TI  - New approaches in radical carbonylation chemistry: fluorous applications and
      designed tandem processes by species-hybridization with anions and transition
      metal species.
AB  - New approaches in radical carbonylation chemistry are described. We have
      successfully integrated tin mediated radical carbonylation chemistry into modern
      fluorous applications and separation techniques. We revealed that radical
      carbonylation reactions can be performed using fluorous tin mediators, such as
      fluorous tin hydride and fluorous allyltin reagents. Fine tuning of the reaction
      conditions resulted in a good efficiency equivalent to conventional tin
      mediators. The tedious procedure of removing organotin byproducts can be
      circumvented through the use of fluorous/organic liquid-liquid extraction or
      fluorous liquid-solid phase extraction with fluorous reverse phase silica (FRPS).
      Also described are newly developed tandem carbonylation reactions that are based
      on species hybridization approaches. Using a radical/anionic hybrid system based
      on zinc-induced one-electron reduction, we achieved a three-component coupling
      reaction consisting of 4-alkenyl iodides, carbon monoxide, and electron-deficient
      alkenes. We observed two types of annulations processes, namely [4 +
      1](radical)/[3 + 2](anionic) and [5 + 1](radical)/[3 + 2](anionic), which lead to
      the production of bicyclo[3.3.0]octanols and bicyclo[3.2.1]octanols,
      respectively. We found a radical/palladium hybrid system to be useful in the
      construction of new cyclic systems that incorporate two or three molecules of
      carbon monoxide.

PMID- 12203909
TI  - Synthesis of aza-heterocycles from oximes by amino-Heck reaction.
AB  - Oxidative addition of oximes to palladium(0) complexes generates
      alkylideneaminopalladium(II) species, which are utilized as key intermediates for
      carbon-nitrogen bond formation. Various aza-heterocycles, such as pyrrole,
      pyridine, isoquinoline, spiroimine, and azaazulene, can be synthesized from O
      pentafluorobenzoyloximes having an olefinic moiety via an intramolecular Heck
      type reaction (amino-Heck reaction) by treatment with a catalytic amount of a
      Pd(0) complex.

PMID- 12203908
TI  - Molecular sieving and sensing with gold nanotube membranes.
AB  - We have developed a new class of synthetic membranes that consist of a porous
      polymeric support that contains an ensemble of gold nanotubes that span the
      thickness of the support membrane. The support is a commercially available
      microporous polycarbonate filter with cylindrical nanoscopic pores. The gold
      nanotubes are prepared via electroless deposition of Au onto the pore walls;
      i.e., the pores act as templates for the nanotubes. We have shown that by
      controlling the Au deposition time, Au nanotubes that have effective inside
      diameters of molecular dimensions (<1 nm) can be prepared. These nanotube
      membranes can be used to cleanly separate small molecules on the basis of
      molecular size. Furthermore, use of these membranes as a novel electrochemical
      sensor is also discussed. This new sensing scheme involves applying a constant
      potential across the Au nanotube membrane and measuring the drop in the
      transmembrane current upon the addition of the analyte. This paper reviews our
      recent progress on size-based transport selectivity and sensor applications in
      this new class of membranes.

PMID- 12203910
TI  - High-throughput approaches for the discovery and optimization of new olefin
      polymerization catalysts.
AB  - The discovery of new olefin polymerization catalysts is currently a time
      intensive trial-and-error process with no guarantee of success. A fully
      integrated high-throughput screening workflow for the discovery of new catalysts
      for polyolefin production has been implemented at Symyx Technologies. The
      workflow includes the design of the metal-ligand libraries using custom-made
      computer software, automated delivery of metal precursors and ligands into the
      reactors using a liquid-handling robot, and a rapid primary screen that serves to
      assess the potential of each metalligand-activator combination as an olefin
      polymerization catalyst. "Hits" from the primary screen are subjected to
      secondary screens using a 48-cell parallel polymerization reactor. Individual
      polymerization reactions are monitored in real time under conditions that provide
      meaningful information about the performance capabilities of each catalyst. Rapid
      polymer characterization techniques support the primary and secondary screens. We
      have discovered many new and interesting catalyst classes using this technology.

PMID- 12203911
TI  - A cDNA resource from the basal chordate Ciona intestinalis.
AB  - The genome of the basal choradate Ciona intestinalis contains a basic set of
      genes with less redundancy compared to the vertebrate genome. Extensive EST
      analyses, cDNA sequencing, and clustering yielded "Ciona intestinalis Gene
      Collection Release 1," which contains cDNA clones for 13,464 genes, covering
      nearly 85% of the Ciona mRNA species. This release is ready for use in cDNA
      cloning, micro/macroarray analysis, and other comprehensive genome-wide analyses
      for further molecular studies of basal chordates.

PMID- 12203912
TI  - The vascular prepattern enhancer trap marks early vascular development in
      arabidopsis.
AB  - Vascular development is a fundamental component of leaf morphogenesis, and the
      mechanisms that control vascular patterning are poorly understood. We report here
      the identification of an enhancer trap line, Vascular Prepattern (VPP), that acts
      as a marker for early vascular development. GUS reporter gene expression in VPP
      was detected in provascular cells from the earliest stages of primary midvein
      formation in leaf primordia and subsequently coincided with the early
      specification of higher order veins. GUS expression in VPP also marks the
      quiescent center cells of the root apical meristem at all stages of root
      development. VPP provides a marker for early vascular development and will be a
      useful tool for studying vascular patterning.

PMID- 12203913
TI  - Cre-mediated recombination in rhombic lip derivatives.
AB  - To study the development of the cerebellum, we generated a transgenic mouse line
      Tg(malpha6-cre)B1LFR that expresses CRE recombinase under the GABA(A) receptor
      alpha6 subunit promoter. In this line, recombination of an R26R reporter allele
      occurred postnatally in granule cells of the cerebellum and dorsal cochlear
      nucleus, as well as in a subset of precerebellar nuclei in the brainstem. All
      neurons in which recombination occurred originated during embryogenesis from the
      rhombic lip. This might be explained by a very early specification event at the
      rhombic lip that primes cells derived from this structure to express the
      transgene during neuronal maturation. As no recombination occurred in the
      inferior olive, it may be derived from a distinct subset of precursors at the
      rhombic lip. No recombination occurred in any of the interneurons in the
      cerebellum (stellate cells, basket cells, and Golgi cells), consistent with the
      hypothesis that they are not derived from the same embryonic tissue as the
      granule cells.

PMID- 12203914
TI  - The porcine SRY promoter is transactivated within a male genital ridge
      environment.
AB  - In mammals the SRY gene functions as a dominant genetic switch for testis
      determination (Gubbay et al.: Nature 346:1128-1135, 1990; Koopman et al.: Nature
      351:117-121, 1991; Sinclair et al.: Nature 346:240-244, 1990). To study SRY
      transcriptional regulation within an evolutionary context, we have generated
      transgenic mice that express green fluorescent protein (GFP) under the control of
      4.5 kb of pig SRY 5' flanking sequences (pSRYp-GFP). Autofluorescence was
      observed in the genital ridges of e11.5 male embryos (18-21 tail somites), and by
      e12.5 (27 tail somites) autofluorescence was observed within the testes cords.
      The expression of the transgene did not display the abrupt termination
      characteristic of endogenous mouse SRY, but rather showed a gradual reduction in
      expression characteristic of human, pig and sheep SRY. Surprisingly, no
      autofluorescence was observed in normal XX genital ridges, although more
      sensitive RT-PCR analysis detected transgene transcription. When the transgene
      was bred into a constitutively male line of mice (Odsex; Bishop et al.: Nat Genet
      26:490-494, 2000), autofluorescence was visible in genital ridges of XX animals,
      in the genetic absence of Sry protein. Via RT-PCR analysis, purified
      autofluorescent cells from e12.5 gonadal ridges expressed mouse SRY but not Oct4
      transcripts, whereas autofluorescent cells from e14.5 gonadal ridges expressed
      MIS but not Oct4 transcripts, in each case consistent with a pre-Sertoli cell
      phenotype. In vitro expression studies performed in CV-1 cells demonstrated that
      pig SOX9 cDNA transactivated the pig SRY promoter but that pig SRY cDNA did not.
      When a SOX9 potential binding site identified at -205 of the pig SRY 5' flanking
      sequences was mutated, the SOX9 transactivation effect was reduced by 70%. This
      site is conserved in the 5' flanking sequences of bovine and human SRY genes but
      not in the mouse gene. Gel retardation assays using this binding site showed
      specific binding to SOX9-enriched nuclear extracts that was competed by excess
      unlabelled binding site but not by mutated binding site. We suggest that pig SRY
      gene is responsive to a testicular environment and propose a model of feedback
      amplification of pig SRY transcription by SOX9.

PMID- 12203915
TI  - A human CD2 minigene directs CRE-mediated recombination in T cells in vivo.
AB  - We have produced a mouse line that expresses the Cre recombinase under the
      regulation of a human CD2 minigene to facilitate Cre-specific recombination in T
      lymphocytes. These mice express Cre in thymocytes and T cells and are capable of
      efficient site-specific recombination as shown in the spleen and thymus, but not
      other tissues. These mice thus provide an excellent resource for the study of
      gene function during thymocyte development and in mature T cells.

PMID- 12203916
TI  - Developmental behavior of gene expression for brown rice thickness under
      different environments.
AB  - The dynamic changes of genetic effects, including main effects, and genotype x
      environment (GE) interaction effects on brown rice thickness (BRT) across
      environments were investigated by using the developmental genetic models. Seven
      cytoplasmic male sterile lines of indica rice (Oryza sativa L.) as females and
      five restoring lines as males were used in a factorial design to produce grains
      of F(1)s and F(2)s in two environments (years) for developmental genetic
      analysis. The results indicate that genetic effects, especially GE interaction
      effects of triploid endosperm genes, cytoplasm genes, and diploid maternal plant
      genes were important to the performance of BRT at various filling stages of rice.
      The BRT was genetically controlled by the net genetic effects of genes expressed
      at the early and late filling stages (1-7 days and 15-21 days after flowering,
      respectively). The differences in net genetic effects under different
      environments for endosperm, cytoplasm, and maternal plant genes were found, and
      the net GE interaction effects were more important to BRT at the early filling
      and mature stages of rice. Some net genetic effects, especially for net cytoplasm
      effects spasmodically expressed, were detected among filling stages. Higher
      additive and cytoplasm main effects, along with their interaction effects, were
      found, which would be useful for selection for BRT in breeding programs. The
      predicated genetic effects at different filling stages show that the parents of
      V20 and Xieqingzao were better than others for improving BRT of progenies.

PMID- 12203917
TI  - Temporal Cre-mediated recombination exclusively in endothelial cells using Tie2
      regulatory elements.
AB  - SUMMARY: The versatility of the bacteriophage Cre/LoxP system is dependent on the
      availability of a spectrum of tissue-specific Cre transgenic mice to address a
      host of biological questions. In this paper, we report on the generation of an
      inducible Tie2Cre transgenic mouse line that facilitates gene targeting
      exclusively in endothelial cells. The temporal manner of recombination is
      feasible through the use of a Cre-estrogen receptor fusion protein ER(T2) and
      was, in practical terms, achieved by feeding the animals the estrogen antagonist
      tamoxifen orally for 5 weeks. High efficiency of recombination was found in the
      vast majority of endothelial cell populations examined, as monitored by an EGFP
      reporter mouse line. Critically, no EGFP expression was observed in any uninduced
      mice. This inducible Cre line will be a very beneficial asset to investigating
      the role of endothelial specific genes in the adult mouse and to induce
      transgenes in the endothelium in an extremely efficient manner. genesis 33:191
      197, 2002.

PMID- 12203919
TI  - A new intracoronary measurement catheter, MetriCath, compared to intravascular
      ultrasound and quantitative coronary angiography in a stented porcine coronary
      model.
AB  - The purpose of this study was to compare measurements by MetriCath to
      intravascular ultrasound (IVUS) and quantitative coronary angiography (QCA). The
      MetriCath system consists of a low-pressure (200 mm Hg) balloon catheter
      connected to a pressure transducer and infusion pump linked to a computer that
      records pressure-volume curves. Cross-sectional area of blood vessels is obtained
      directly from the unrestrained and in-stent pressure-volume measurements. We
      compared stent cross-sectional area measurements by MetriCath, IVUS, and QCA in a
      porcine stented coronary artery model. Comparison of area measurements in 14
      stents showed no significant differences between the three methods (P = 0.66). On
      average, values differed 0.37 +/- 0.60 mm(2) between MetriCath and QCA, 0.13 +/-
      0.55 mm(2) between MetriCath and IVUS, and 0.22 +/- 0.80 mm(2) between IVUS and
      QCA. This corresponds to 6.2% +/- 10%, 3.0% +/- 9.0%, and 3.1% +/- 12.9% relative
      difference from the average of two corresponding measurements. Linear regression
      analysis showed excellent correlation between measurements (r = 0.99 for all
      comparisons). The differences in in-stent area measurements between MetriCath and
      both QCA and IVUS were small. Considering the ease and rapidity of obtaining
      MetriCath results, this technique may form an alternative to the others in
      evaluating stent expansion. Based on these findings, clinical evaluation seems
      warranted.

PMID- 12203920
TI  - Anatomical and physiological assessment of the coronary artery: is there a
      business for intracoronary diagnostics?

PMID- 12203921
TI  - Percutaneous management of access site complications.
AB  - Percutaneous cardiac catheterization and endovascular procedures are associated
      with complications at the vascular access site. While surgery has been the
      traditional treatment for vascular access complications, the current state of the
      art permits percutaneous management of many access site complications. Surgical
      repair may be required only when percutaneous methods fail, are not available, or
      are unsuitable.

PMID- 12203922
TI  - Rheolytic thrombectomy and platelet glycoprotein IIb/IIIa blockade for stent
      thrombosis.
AB  - Conventional transcatheter-based strategies result in good procedural success but
      poor clinical outcome in the treatment of intracoronary stent thrombosis. A
      combined approach of mechanical thrombus burden reduction using AngioJet
      rheolytic thrombectomy with adjunctive glycoprotein (GP) IIb/IIIa antagonists has
      not been studied. Between July 1998 and August 2000, 15 patients (17 procedures)
      underwent AngioJet thrombectomy for stent thrombosis at the Beth Israel Deaconess
      Medical Center. Patients were followed clinically through 6 months following the
      AngioJet procedure. All patients presented with signs of acute myocardial
      infarction at a median of 6 days following the original stenting procedure. Most
      vessels (88%) were occluded at presentation. A GP IIb/IIIa inhibitor was
      administered during 16 of the 17 procedures. Rheolytic thrombectomy resulted in
      complete removal of filling defects in all reviewed cases and led to significant
      improvement in lumen diameter and TIMI flow with reduction in the thrombotic
      lesion length (all P values < 0.05). Angiographic success (< 30% residual
      stenosis, TIMI 3 flow) was attained in all but one procedure. No patient required
      emergent coronary bypass grafting, repeat coronary angioplasty, or died in
      hospital. At 6 months, there were no deaths and repeat revascularization was
      performed in four patients (29%). A combined approach of rheolytic thrombectomy
      with adjunctive GP IIb/IIIa blockade was highly effective in resolving stent
      thrombosis and was associated with favorable acute and long-term outcomes.

PMID- 12203923
TI  - A case of an entrapped rotational atherectomy burr.

PMID- 12203924
TI  - Paradoxical embolization of a fractured guidewire: successful retrieval from left
      atrium using a snare device.
AB  - In adults, paradoxical embolization of catheters or guidewire fragments related
      to central venous catheterization is a rare phenomenon. Reports of successful
      percutaneous retrieval of foreign bodies from the left atrium is also rare. We
      describe the successful percutaneous retrieval of a fractured guidewire that had
      undergone paradoxical embolization to the left atrium in an adult patient.

PMID- 12203925
TI  - Successful treatment of iatrogenic renal artery perforation with an autologous
      vein-covered stent.
AB  - A 72-year-old woman developed severe flank pain associated with hemodynamic
      compromise immediately after a J-curve guidewire was inadvertently advanced into
      the right renal artery during cardiac catheterization. Contrast extravasation
      consistent with perforation of the main renal artery was seen on abdominal
      angiography. The perforation was successfully sealed using a premounted coronary
      stent that was covered with an autologous antecubital vein. Wide stent patency
      without aneurismal dilatation was confirmed on a 2-year follow-up renal
      angiogram.

PMID- 12203926
TI  - Artery perforation during catheterization: fighting with a catastrophe.

PMID- 12203927
TI  - MRI findings in a case of transient cortical blindness after cardiac
      catheterization.
AB  - The magnetic resonance imaging findings in a case of transient cortical blindness
      (TCB) after cardiac catheterization are described for the first time. In
      addition, a literature review of TCB, comparison with reversible posterior
      leukoencephalopathy, and a hypothesis regarding the pathophysiology of TCB are
      presented.

PMID- 12203928
TI  - Iodide-induced sialadenitis complicating coronary angiography.
AB  - Sialadenitis is an uncommon complication of intravenous administration of
      iodinated contrast medium. We present two cases of iodide-induced sialadenitis
      following coronary angiography. Clinical features and clues to differentiation
      from suppurative sialadenitis are discussed. The mechanism for aseptic iodide
      induced sialadenitis remains unclear, but prognosis with conservative treatment
      is apparently good. Sialadenitis may recur with subsequent administration of
      contrast medium.

PMID- 12203929
TI  - Distal emboli protection in patients undergoing percutaneous coronary
      intervention after a recent myocardial infarction.
AB  - Devices to prevent distal atheroembolization are an important addition to the
      armamentarium of an interventional cardiologist. We report the use of PercuSurge,
      a distal balloon occlusion device, in two patients with recent myocardial
      infarction of differing etiologies. The first case is a patient with an old
      degenerated vein graft with thrombotic occlusion of greater than 48-hr duration
      and the second case is a patient with an embolic myocardial infarction in a
      native coronary artery. In both cases, significant thromboembolic debris was
      aspirated with technical success and no complications. These cases illustrate use
      of the PercuSurge device in patients after a recent myocardial infarction for
      preserving distal myocardial perfusion and microvascular integrity.

PMID- 12203930
TI  - Intravascular ultrasound diagnosis of a venous obstruction not visualized by
      conventional venography: a case report.

PMID- 12203931
TI  - No delayed restenosis at 18 months after implantation of sirolimus-eluting stent.
AB  - Sirolimus-eluting stent is emerging as a potential solution for the prevention of
      restenosis. Recently, a sustained suppression of neointimal proliferation 12
      months after implantation of this stent was reported. This is the first report of
      angiographic and IVUS images 18 months after the implantation of a sirolimus
      eluting stent.

PMID- 12203932
TI  - Drug-eluting stents for the prevention of restenosis: Standing the test of time.

PMID- 12203933
TI  - A case of refractory in-stent restenosis: failed RE-WRIST.

PMID- 12203934
TI  - Successful treatment of a femoral artery pseudoaneurysm mimicking a deep venous
      thrombosis following cardiac catheterization.
AB  - Access site pseudoaneurysms are uncommon but well-known complications of cardiac
      catheterization. We report the first known case of a pseudoaneurysm mimicking the
      presentation of a deep venous thrombosis by causing extrinsic compression of the
      venous system. The patient had complete resolution of the pseudoaneurysm and his
      symptoms following treatment with ultrasound-guided percutaneous thrombin
      injection.

PMID- 12203935
TI  - AngioJet thrombectomy and stenting for reperfusion in acute MI complicated with
      cardiogenic shock.
AB  - AngioJet thrombectomy (AJ) has been shown to be safe and effective in treatment
      of acute myocardial infarction (AMI). However, use of AJ has not been studied
      extensively in AMI with cardiogenic shock (CS). Clinical outcomes in 19 patients
      with CS and treated with AJ were retrospectively analyzed. Immediate stenting was
      also performed. Procedure success (final diameter stenosis < 50% and TIMI flow >
      or = 2) was achieved in 95%, with final TIMI 3 flow in 89%. Clinical success
      (procedure success without major in-hospital cardiac events) was achieved in 68%.
      There were five in-hospital deaths and no patients experienced stroke or required
      emergent bypass surgery. At 30-day follow-up, there were no additional deaths or
      stroke, and two patients had undergone target vessel revascularization. AJ is
      relatively safe and effective in the setting of AMI complicated with CS, allowing
      for immediate definitive treatment. This strategy may offer improved mortality in
      these high-risk patients.

PMID- 12203936
TI  - Hypoplastic left heart syndrome with intact atrial septum: levoatriocardinal vein
      stent placement as a bridge to surgery.
AB  - Infants with hypoplastic left heart syndrome, an intact atrial septum and
      pulmonary venous hypertension, are critically ill and have a poor prognosis. This
      case describes relief of severe pulmonary edema in such a patient by stent
      placement in a stenotic levoatriocardinal vein, with subsequent successful
      surgical palliation.

PMID- 12203938
TI  - Pulmonary valvuloplasty in a case of vascular Ehlers-Danlos syndrome.
AB  - A 15-year-old girl with known Ehlers-Danlos syndrome (EDS) type IV presented with
      severe pulmonary valve stenosis requiring intervention. We describe successful
      pulmonary valvuloplasty using a 90% balloon/annulus angioplasty balloon. The
      procedure was complicated by early restenosis suggesting an abnormal scarring
      response in EDS IV.

PMID- 12203937
TI  - First closure of a large patent ductus arteriosus in an infant with an angulated
      nitinol plug.
AB  - We report the first human implantation of an angulated plug in a 5 mm PDA in a
      child of 11 kg. Implanted through a 5 Fr sheath, the plug showed excellent
      anatomical alignment. Complete occlusion was documented after 6 hr. This device
      will extend the limits for interventional closure of PDA.

PMID- 12203939
TI  - Catheter closure of accessory pulmonary blood flow after bidirectional Glenn
      anastomosis using Amplatzer duct occluder.
AB  - Additional source of pulmonary blood flow in patients with bidirectional
      cavopulmonary anastomosis (Glenn shunt) may cause elevation of the pulmonary
      artery pressure precluding safe completion of the Fontan operation. A case is
      presented with single-ventricle bidirectional cavopulmonary anastomosis and
      additional flow from the ventricle to the pulmonary artery resulting in elevated
      Glenn pressure. The communication was successfully occluded using Amplatzer duct
      occluder with satisfactory reduction in the Glenn pressure.

PMID- 12203941
TI  - The DPT-1 trial: a negative result with lessons for future type 1 diabetes
      prevention.
AB  - The author comments on the DPT-1 Trial and why the observed negative outcome in
      preventing diabetes in first-degree relatives of type 1 diabetic patients by
      parenteral insulin administration may have occurred and what can be gathered from
      this large study. There were three main lessons to be learned from the DPT-1
      Trial as follows. (1) Large preventive trials of type 1 diabetes are feasible in
      first-degree relatives of type 1 diabetic patients and other preventive
      approaches may be now envisaged. (2) The natural history of type 1 diabetes, at
      least in its final years before clinical onset, has been elucidated and
      reiterates the relevance of our present predictive tools (autoantibodies) for
      identifying individuals at risk for the disease. (3) Strict follow-up of enrolled
      subjects in trials permits an earlier diagnosis of the disease with less
      frequency of ketoacidosis and implementation of insulin therapy when higher C
      peptide levels are present. DPT-1 has paved the way on how to proceed and new
      trials will be planned benefiting from such experience.

PMID- 12203942
TI  - Neurovascular disease, antioxidants and glycation in diabetes.
AB  - People with diabetes are ten to fifteen times more likely to have a lower limb
      amputation (LLA) than non-diabetic individuals. Fifteen percent of people with
      diabetes will develop a foot ulcer during their lifetime, the rate of major
      amputation amongst diabetic individuals continues to rise, foot problems remain
      the commonest reason for diabetes-related hospitalisation and recurrence rates in
      patients with previous foot ulcers are 50% or more. Hyperglycaemia-induced
      oxidative stress has been shown to result in decreased nerve conduction velocity,
      and decreased endoneural blood flow-both precursors for neuropathy. Vitamin
      antioxidants have been shown to be effective therapy in experimental models in
      reducing free radical species and inhibiting the oxidative process in diabetes
      subjects. Little work has been published, however, regarding the dietary use of
      antioxidants from foods, and their specific effects on neurovascular disease and
      glycation within the diabetes population. Aetiological and prevention studies
      with dietary antioxidants from foods aimed at the complex nature of foot problems
      in diabetes are needed.

PMID- 12203943
TI  - Considerations on blood glucose management in Type 2 diabetes mellitus.
AB  - In recent years the benefits of more intensive management in preventing or
      delaying the development and progression of diabetic complications have been well
      documented. What is not as well documented is how to motivate the person with
      diabetes to manage the condition, how to set, assess and quantify glucose goals,
      and the glucose variables that should be routinely measured. This review
      discusses the importance of setting targets and communicating them in a way that
      the patient understands. When aiming for a glycaemia target, balance is required
      (1) between achieving reduction of complications and causing an increased degree
      of hypoglycaemia, and (2) between what is achievable and what degree of benefit
      is gained. Target values given in guidelines should be adapted by the clinician
      to take into account the patient's susceptibility to hypoglycaemia, stage and
      type of complications, age and life expectancy, co-morbidity, social environment,
      understanding of the steps required and level of commitment to the treatment.
      Several suggestions are given regarding possible improvements and amendments to
      existing guidelines for diabetes management in treating to glucose goal. For
      example, attention should be drawn to the need to individualize goals and to
      consider education, long-term support, patient needs and treatment outcome when
      formulating diabetes management plans. The relative properties of the different
      glucose variables-fasting plasma glucose (FPG), postprandial plasma glucose
      (PPG), glycated haemoglobin A(1c) (HbA(1c)), and glycated protein-in terms of
      their convenience of measurement, usefulness and relevance to the physician and
      patient are also evaluated. When prioritising the variables to be measured it is
      suggested that where feasible, HbA(1c) should be the standard measurement by
      which to gauge risk and treatment efficacy. Serial measurements should be made
      and, where possible, the use of blood glucose meters encouraged, in order to
      obtain a blood glucose profile for the patient.

PMID- 12203944
TI  - Haemodynamics in microvascular complications in type 1 diabetes.
AB  - Type 1 diabetes is commonly associated with microvascular complications. Most of
      the microvascular blood vessels are involved but those in the kidney, retina and
      large nerves exhibit the more significant pathology. Haemodynamic and metabolic
      factors both alone and through the activation of a common pathway contribute to
      the characteristic dysfunction observed in diabetic vasculopathy. The
      haemodynamic abnormalities in type 1 diabetes are characterized by increased
      systemic blood pressure and altered blood flow with subsequent activation of
      various vasoactive factors, which can contribute to the maintenance of the
      haemodynamic alterations and to the development and progression of the
      microvascular complications. These vasoactive factors include vasoconstrictors
      such as angiotensin II, and endothelin, as well as vasodilators such as nitric
      oxide (NO). Systemic hypertension and vasoactive factors independently and in
      interaction with the metabolic pathway activate intracellular second messengers,
      nuclear transcription factors and various growth factors which lead to the
      typical functional and structural alterations of diabetic microvascular
      complications. Therapeutic strategies involved in the management and prevention
      of diabetic complications currently include antihypertensive agents, particularly
      those that interrupt the renin-angiotensin system. Further understanding of the
      interactions among the vasoactive factors, the intracellular second messengers
      and the growth factors may help to identify novel strategies to influence the
      action of the vasoactive factors. These novel therapies, together with specific
      inhibitors of the metabolic pathway or the common pathway, may provide the
      possibility of preventing or even reversing the progression of diabetic
      microvascular complications.

PMID- 12203945
TI  - alpha2-Heremans Schmid glycoprotein, a putative inhibitor of tyrosine kinase,
      prevents glucose toxicity associated with cardiomyocyte dysfunction.
AB  - BACKGROUND: Diabetes leads to impaired glucose metabolism and insulin signaling
      in the heart, which may contribute to the development of diabetic cardiomyopathy.
      Insulin stimulates tyrosine phosphorylation of the insulin receptor and insulin
      receptor substrates. A two-fold increase in insulin-stimulated tyrosine
      phosphorylation has been reported in diabetic myocardium. The aim of the present
      study was to examine the effect of a putative inhibitor of tyrosine kinase
      phosphorylation, alpha(2)-Heremans Schmid glycoprotein (AHSG), on the mechanical
      dysfunction under a simulated diabetic environment. METHODS: Isolated ventricular
      myocytes from adult rats were maintained for 24 h in either normal glucose (NG,
      5.5 mM) or high glucose (HG, 25.5 mM) medium with 10(-7) M insulin, and in the
      absence or presence of AHSG (50 micro g/ml). Contractile indices analyzed
      included: peak shortening (PS), time-to-PS (TPS), time-to-90% relengthening
      (TR(90)) and area underneath shortening and relengthening (Area/PS). RESULTS:
      Myocytes maintained in HG medium displayed reduced PS and prolonged TPS/TR(90),
      with enhanced area, compared to the NG myocytes. Interestingly, these HG-induced
      mechanical dysfunctions were abolished by AHSG. Removal of insulin from the
      culture medium did not affect the basal myocyte mechanics, but prevented AHSG
      from completely protecting against the HG-induced mechanical defects (i.e. HG
      induced prolongation of TR(90) and area were only partially attenuated by AHSG in
      the absence of insulin). CONCLUSIONS: The present data support the notion of
      tyrosine phosphorylation in the pathogenesis of diabetic cardiomyopathy, and
      implicate the therapeutic value of tyrosine kinase phosphorylation inhibitors.

PMID- 12203946
TI  - Alpha2-HS glycoprotein: a protein in search of a function.
AB  - In this issue (pp. 305-310) Jun Ren and Amy J. Davidoff author an article
      entitled 'Alpha2-HS glycoprotein, a putative inhibitor of tyrosine kinase,
      prevents glucose toxicity associated with cardiomyocyte dysfunction'. The protein
      responsible for this biological activity has recently come to the forefront of
      research on the biological activity of plasma proteins.

PMID- 12203947
TI  - Effects of protein kinase Cbeta inhibition on neurovascular dysfunction in
      diabetic rats: interaction with oxidative stress and essential fatty acid
      dysmetabolism.
AB  - BACKGROUND: Elevated protein kinase C (PKC) activity is thought to play a
      substantial role in the aetiology of diabetic microvascular complications, the
      PKCbeta isoform being identified as particularly important. Neuropathy has a
      vascular component; therefore, one aim was to assess whether the PKCbeta
      inhibitor, LY333531, could correct nerve conduction velocity (NCV) and perfusion
      deficits in diabetic rats. Neurovascular dysfunction also depends on oxidant
      stress and impaired omega-6 essential fatty acid metabolism; correctable by
      antioxidant and gamma-linolenic acid (GLA) treatments, respectively. A second aim
      was to assess whether there were interactions between these mechanisms and
      PKCbeta-mediated effects. METHODS: Diabetes was induced by streptozotocin;
      duration was 8 weeks. NCV was monitored and blood flow was assessed by hydrogen
      clearance microelectrode polarography. RESULTS: Diabetes caused 19.7% and 13.9%
      reductions in sciatic motor and saphenous sensory NCV, respectively. Two weeks of
      LY333531 treatment dose-dependently corrected these deficits. A dose of 10 mg kg(
      1) day(-1) gave non-diabetic NCV values and also completely corrected a 50%
      diabetic reduction in sciatic endoneurial blood flow. Low-dose (0.25 mg kg(-1)
      day(-1)) LY333531 had modest effects ( approximately 20% correction) on NCV and
      sciatic perfusion. However, when combined with equi-effective doses of the
      antioxidants vitamin E or alpha-lipoic acid, or GLA, motor and sensory NCV and
      sciatic nerve perfusion were in the non-diabetic range. The joint effect was
      equivalent to that of the 10 mg kg(-1) day(-1) LY333531 dose, demonstrating
      synergism between PKCbeta, oxidative stress and essential fatty acid mechanisms.
      CONCLUSIONS: LY333531, alone or combined with antioxidants or GLA, could form the
      basis for therapeutic intervention in neuropathy, which requires assessment in
      clinical trials.

PMID- 12203949
TI  - Continuous glucose monitoring in managing diabetes in children.
AB  - Continuous glucose monitoring (CGM) devices have now been added to the repertoire
      of technological devices useful in the management of patients with diabetes. In
      this issue, Schiaffini and colleagues confirm and extend published data
      describing the benefits of CGM in diabetic children. Specifically, such
      monitoring enables clinicians to detect occult hypoglycemia not otherwise
      discernable with intermittent testing of blood glucose. Although results of
      monitoring are not yet available in real time, the data can be used to adjust
      insulin regimens to allow more effective glycemic control. This is especially
      important in the pediatric population for whom strict glycemic control has
      traditionally been limited owing to concerns about the negative effects of
      hypoglycemia on the developing central nervous system. Additionally, postprandial
      hyperglycemia can be more readily detected and controlled. CGM provides new and
      important information not necessarily provided by measurement of HbA1c, and will
      likely prove an indispensable adjunct to diabetes care. Finally, this procedure
      has potential applications in the diagnosis and management of patients with other
      metabolic disorders.

PMID- 12203948
TI  - The Continuous Glucose Monitoring System (CGMS) in type 1 diabetic children is
      the way to reduce hypoglycemic risk.
AB  - BACKGROUND: Diabetic children treated with intensive insulin therapy are showing
      a dangerous increase in severe hypoglycemic episodes. The Continuous Glucose
      Monitoring System (CGMS) allows glycemic profiles to be monitored over a 72-h
      period. The aim of the present study was to evaluate whether this system is
      sufficiently sensitive to detect asymptomatic hypoglycemia, and to determine if
      its periodic application would help to minimize the hypoglycemic risk in children
      with type 1 diabetes mellitus (T1DM). METHODS: Twenty-seven T1DM children (age
      range 6-13.1 years) were enrolled in the study. The sensor was inserted
      subcutaneously in each patient and the standard four or five registrations of
      capillary glycemia per day were performed. Eighteen patients continued in the
      study and the glucose sensor was again inserted after a 6-week interval. At the
      beginning and end of the study, fructosamine, glycosylated hemoglobin (HbA(1c)),
      median glycemia, number and duration of hypoglycemic events and insulin
      requirement were evaluated. RESULTS: A significantly higher number of
      asymptomatic hypoglycemic events was revealed by CGMS in comparison with the
      standard system (3.6 +/- 2.3 vs 0.7 +/- 0.9; p < 0.0001). In patients who
      continued in the study, insulin therapy adjustments reduced the incidence of
      hypoglycemic events (2.5 +/- 1.7 vs 3.9 +/- 2.2; p < 0.05). At the 6-week point,
      the fructosamine level was reduced (330 +/- 30 vs 349 +/- 24 micro mol/l; p <
      0.05). CONCLUSIONS: The CGMS is a useful device not only for detecting
      unrecognized hypoglycemia, but also for modifying insulin therapy in order to
      reduce hypoglycemic events. The system appears to be useful in avoiding long
      exposure to hypoglycemia.

PMID- 12203951
TI  - Impact of selenium and other trace elements on the endangered adult razorback
      sucker.
AB  - A study was conducted with endangered the razorback sucker (Xyrauchen texanus) to
      determine if environmental exposure to selenium in flooded bottomland sites
      affected survival, growth, and egg-hatching success. Adults were stocked at three
      sites adjacent to the Colorado River near Grand Junction, Colorado, in July 1996:
      hatchery ponds at Horsethief Canyon State Wildlife Area (referred to here as
      Horsethief; the reference site), a diked tertiary channel at Adobe Creek, and
      North Pond at Walter Walker State Wildlife Area (WWSWA). Fish were collected in
      April 1997 and spawned. After two spawnings adults from the three sites were held
      at Horsethief for an 86-day selenium depuration period. Selenium concentrations
      at Horsethief were 1.4-3.0 microg/L in water, 0.8-0.9 microg/g in sediment, 4.5
      microg/g in muscle plug, and 6.0 microg/g in eggs; at Adobe Creek, <0.7-4.5
      microg/L in water, 1.2-2.5 microg/g in sediment, 16-20 microg/g in zooplankton,
      9.6 microg/g in muscle plug, and 40 microg/g in eggs; and at North Pond, 3.2-17
      microg/L in water, 16-94 microg/g in sediment, 32-48 microg/g in zooplankton, 14
      microg/g in muscle plug, and 55 microg/g in eggs. During the depuration period,
      when adults from Adobe Creek and North Pond were held at Horsethief, the fish
      lost 7%-13% of their selenium burden in 59 days and 14%-21% in 86 days. Larvae
      from North Pond adults had the most deformities, followed by Adobe Creek adults,
      with the fewest deformities found in the Horsethief adults.

PMID- 12203952
TI  - Carbon disulfide cytotoxicity on cultured cardiac myocytes of rats.
AB  - Although epidemiological studies have suggested that carbon disulfide produces
      cardiovascular effects in occupationally exposed workers, little is known about
      its cellular mechanism. The purpose of the present study was to evaluate the
      functional and histological effects on cardiac myocytes cultured under a
      condition of carbon disulfide exposure. Cardiac myocytes were isolated from
      neonatal rat ventricles by trypsin, dispersed and cultured for 3 days in a full
      Dulbecco's Modified Eagle Medium containing 2% calf serum. Then the myocytes
      (10(6) myocytes/mL) were incubated with carbon disulfide at concentrations of 0,
      20, 40, and 80 micromol/mL for 24 h. The beating arrest rate of myocytes for each
      group was examined, succinodehydrogenase (SDH) activity in the myocardial cells
      was assessed using a cytochemical method, and a morphological examination was
      performed. We found that the beating arrest rate of cardiac myocytes increased
      with increasing exposure levels. Vacuolization and pseudopodia could be seen in
      the cytoplasm of the exposed group. SDH activity decreased with increasing
      exposure levels. The results suggest that CS2 has a direct and dose-dependent
      cytotoxic effect. The biochemical mechanism may be a reduction of the
      availability of energy (adenosine triphosphate) to cardiac myocytes, resulting in
      a decrease of contractility by lack of energy.

PMID- 12203953
TI  - Determination of chiral ratio of o,p-DDT and o,p-DDD pesticides on
      polysaccharides chiral stationary phases by HPLC under reversed-phase mode.
AB  - A simple and reliable HPLC method for the chiral resolution of o,p-DDT and o,p
      DDD is described. The enantiomeric resolution of o,p-DDT and o,p-DDD has been
      achieved on Chiralpak AD-R, Chiralcel OD-R, and Chiralcel OJ-R chiral stationary
      phases. The mobile phases used were acetonitrile-water (50:50 [v/v]) and
      acetonitrile-2-propanol (50:50 [v/v]) at a flow rate of 1.0 mL/min. For both
      pesticides detection was done at 220 nm. The values for o,p-DDT of alpha and R(s)
      varied from 1.24 to 2.52 and from 0.80 to 2.47, respectively. The values of alpha
      and R(s) for o,p-DDD were 1.26 and 0.60, respectively.

PMID- 12203954
TI  - Acute toxicity and bioaccumulation of pesticide Diazinon in red tilapia
      (Oreochromis niloticus x Mossambicus albina).
AB  - Young red tilapias were exposed for 96 h to each one of 6 concentrations of the
      pesticide Diazinon in order to determine the pesticide's acute toxicity level.
      After the ascertaining the lethal concentration (LC50) at 96 h, a level 10 times
      lower was selected for the bioaccumulation study of the pesticide in male and
      female specimens exposed for 9 days. The elimination process was carried out for
      10 days beginning right after the conclusion of the accumulation process.
      Analytical procedures were developed and used for the studies of acute toxicity
      and bioaccumulation of Diazinon in red tilapia. A lethal concentration [LC50 (96
      h)] of 3.85 mg/L was found, and steady-state accumulation, at a concentration of
      28.45 mg/kg, was reached at 7.72 days. In the elimination process a concentration
      of 0.29 mg/kg was found in tilapia tissue by the sixth day after the fish were
      moved to clean water, and it continued to decrease quickly toward nondetectable
      levels.

PMID- 12203955
TI  - Genotoxicity of cyanobacterial extracts containing microcystins from Polish water
      reservoirs as determined by SOS chromotest and comet assay.
AB  - Toxicity of cyanobacterial blooms, an increasing problem around the world, is
      connected to the increase in bloom samples containing microcystins, caused by
      excessive eutrophication of drinking- and recreational water reservoirs.
      Microcystins are the most common group of cyanobacterial hepatotoxins. In Poland
      they are produced mainly by the Microcystis genus. The toxicity of microcystins
      has been well documented, but investigation into their genotoxicity has been
      insufficient relative to the study of their overall toxicity. Therefore, the aim
      of this study was the estimation and comparison of the genotoxicity of
      cyanobacterial extracts with microcystins (CEMs) using the SOS chromotest
      (bacterial test) with Escherichia coli PQ37 and the comet assay with human
      lymphocytes. Cyanobacterial bloom samples were collected in the summer months
      from two Polish water reservoirs, one at Sulejow and one at Jeziorsko. The SOS
      chromotest, which used prokaryotic cells (without metabolic activation), and the
      comet assay, which used eukaryotic cells, both indicated the potential genotoxic
      effect of CEMs. Cyanobacterial extracts caused DNA damage in human lymphocytes in
      vitro. The maximum level of DNA damage was observed after 12 h incubation with
      CEMs. The bacterial test indicated a dependence of the degree of CEM
      genotoxicity, the composition, and the concentration of microcystins in each
      bloom sample examined with the time of exposure. Differences between the
      genotoxicity of cyanobacterial extract and the standard microcystin-LR were
      noticeable. This was probably caused by the interaction of different microcystin
      variants. The results showed that CEMs from Polish water reservoirs were
      genotoxic, which was reflected by the stimulation of the SOS repair system in
      bacterial cells (SOS chromotest) and by the damage induced in DNA in human
      lymphocytes (comet assay).

PMID- 12203956
TI  - [ADMAdda5]-microcystins in Planktothrix agardhii strain PH-123 (cyanobacteria)-
      importance for monitoring of microcystins in the environment.
AB  - Two major and two minor microcystins (MCYST) were isolated from a hepatotoxic
      Danish strain of Planktothrix agardhii (Gomont) Anagnostidis et Komarek by
      reversed-phase high-performance liquid chromatography. The microcystins were
      characterized by UV spectroscopy, amino acid analysis, fast atom bombardment mass
      spectrometry (FABMS), and high-resolution FABMS. The major microcystins were
      further analysed by collisionally induced tandem electrospray ionization MS. The
      microcystins were found to be demethylated variants of MCYST-HtyR (homotyrosine
      arginine) and MCYST-LR (leucine-arginine). The two major microcystins contained
      an acetyl-demethyl variant (ADMAdda) of 3-amino-9-acetoxy-2,6,8-trimethyl-10
      phenyldeca-4,6-dienoic acid (Adda). This is the first report of [ADMAdda5]
      microcystins in Planktothrix. The two [ADMAdda5]-microcystins inhibited protein
      phosphatase activity but showed low cross-reactivity with antibodies of an enzyme
      linked immunosorbent assay (ELISA), emphasizing the potential underestimation of
      the toxicity of natural blooms dominated by Planktothrix when microcystin content
      is quantified using only an ELISA.

PMID- 12203957
TI  - Cyanobacterial toxin research and its application in Germany: a review of the
      current status.

PMID- 12203958
TI  - Microcystin-producing cyanobacteria in recreational waters in southwestern
      Germany.
AB  - Toxin-forming species of freshwater cyanobacteria have been detected in all parts
      of Germany. Because of the high number of lakes (more than 2000) in Baden
      Wurttemberg, in southwestern Germany, only a representative selection of lakes
      (155) was intensively monitored for mass development of cyanobacteria and the
      formation of toxins in 1999. Nutrients, dominant algal species, chlorophyll, and
      toxins were determined from waters with cyanobacterial blooms. Toxin analyses
      were performed using HPLC, the PP1 inhibition test, and the microcystin ELISA. In
      45% of the monitored lakes, the phytoplankton assemblage consisted mainly of
      cyanobacteria; in an additional 24% of the lakes cyanobacteria were detected.
      More than 26% of the lakes contained toxigenic cyanobacteria. The highest amount
      of microcystins detected outside scum areas was 11-560 microg/L. In relation to
      biomass, cyanobacteria contained up to 1100 microg/g dry matter and up to 2.6
      microg/microg Chl a. The dominant form of microcystin detected was microcystin
      LR, one of the most toxic known microcystins. The results of the present study
      have been used to develop a stepwise monitoring scheme for lakes with permanent
      cyanobacterial populations to protect human health and livestock.

PMID- 12203959
TI  - Applications of MALDI-TOF MS analysis in cyanotoxin research.
AB  - Recent advances in analytical chemistry have provided an array of techniques to
      analyze cyanotoxins in a variety of samples. Mass spectral analysis by matrix
      assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF
      MS) has proven to be a reliable and rapid tool to detect and identify microcystin
      variants in very small samples such as single Microcystis colonies. Mass signals
      presumptive of microcystin variants can be characterized further and identified
      by postsource-decay fragmentation and comparison of observed fragment spectra
      with theoretical ones or with those of pure reference compounds. By analyzing
      Microcystis colonies from water blooms, the high metabolic diversity among
      individual colonies in the communities could be established. For monitoring
      microcystins in environmental samples, MALDI-TOF MS can provide considerable
      support to HPLC by identifying microcystin variants not available as purified
      standards, especially in Planktothrix-dominated blooms in which demethylated
      variants are predominant. A short description of the principles of MALDI-TOF MS
      is provided, followed by examples of its application and a discussion of its
      potential use in cyanotoxin research.

PMID- 12203960
TI  - Production of drinking water from raw water containing cyanobacteria--pilot plant
      studies for assessing the risk of microcystin breakthrough.
AB  - Toxins in cyanobacteria are a recognized risk in the treatment of drinking-water
      treatment. Cyanotoxins can occur in two modifications: cell bound and dissolved
      in water. The process of toxin release may occur naturally, but it also may be
      induced through the processes of drinking-water treatment. Both causes of release
      are relevant to the safety of drinking water. This study investigated cyanotoxin
      release and elimination through different treatment trains in systematic pilot
      scale studies with water from the Weida Reservoir, in Thuringia, Germany. The
      Weida Reservoir is a dimictic mesoeutrophic reservoir typical for a number of
      mountainous areas in Europe, with Planktothrix rubescens as the dominant
      phytoplankton species, and shows a characteristic seasonal pattern of population
      development and microcystin occurrence. To assess the risk of microcystin
      breakthrough, the pilot-scale results as well as results of laboratory-scale
      experiments were used for developing a kinetic model of toxin release in relation
      to elimination. By calculating removal efficiency of total microcystins (cell
      bound and dissolved) for different treatment trains, raw water quality was
      related to the quality targets for finished water, and breakthrough risks could
      be calculated for given treatment trains and varying cyanobacterial population
      densities in the reservoir.

PMID- 12203961
TI  - Removal of microcystins by slow sand filtration.
AB  - To assess the elimination potential of slow sand filters for cyanobacterial
      hepatotoxins (microcystins), two full-scale experiments were conducted using the
      German Federal Environment Agency's experimental field in Berlin, Germany. One
      experiment was carried out with dissolved microcystins extracted from a
      cyanobacterial bloom on one of Berlin's lakes, dosed as short-term, single-pulse
      application. The other experiment simulated natural conditions more closely, with
      a longer-term exposure of the filter to living cyanobacterial cells (collected
      from the same lake) so that most toxins were initially contained inside the
      cells. The microcystins were detected by ELISA and HPLC/photodiode array detector
      and subsequently identified by MALDI-TOF MS. The experiment with dissolved
      microcystins yielded very high elimination rates (>95%) inside the filter bed
      attributed to biodegradation, whereas retardation by adsorption was low. The
      obtained half-lives for the microcystins detected by ELISA were about 1 h. The
      second experiment, which was with mostly cell-bound microcystins, showed similar
      results during the first days after application of cyanobacteria (elimination
      >85%). As the population declined in late autumn, the proportion of extracellular
      to cell-bound microcystins increased. At the same time the elimination rates
      declined to values <60%. This decline is most likely attributable to retarded
      biodegradation at temperatures of <4 degrees C. Altogether the results of the
      experiments show that under moderate temperatures, with an intact schmutzdecke
      (biofilm) with previous contact with microcystins, slow sand filtration is an
      effective treatment for eliminating microcystins from drinking water.

PMID- 12203962
TI  - Toxicity assessment of cyanobacterial toxin mixtures.
AB  - A method is presented for the toxicity assessment of mixtures of cyanobacterial
      toxins with hepatotoxic, neurotoxic, and carcinogenic effects. The method is
      based on the derivation of toxicity equivalent factors obtained from
      toxicological data presented for cyanobacterial toxins in the literature and on
      the use of toxicity equivalents in analogy with the method used for
      polychlorinated dibenzo[p]dioxins and dibenzofurans. Because the method easily
      can include all toxicological data for cyanobacterial toxins at any time, the
      quality of the toxicity assessment of these toxins can be increased continuously
      depending on data availability. Generally, all toxicologically relevant
      cyanobacterial toxins for which data are available should be included in this
      assessment. The method is considered useful in the toxicity assessment of
      cyanobacterial toxin mixtures in surface water bodies and in drinking water. When
      using the total sum of the toxicity equivalents, the approach proposed here seems
      to lead to a more realistic toxicity assessment of cyanobacterial toxin mixtures
      than does the worst-case approach. However, the availability of data about acute
      and, especially, chronic toxicity must be increased significantly in the future
      in order to establish toxicologically validated exposure limit values for
      cyanobacterial toxins, especially those with hepatotoxic, neurotoxic, and
      carcinogenic effects.

PMID- 12203963
TI  - Effects of microcin SF608 and microcystin-LR, two cyanotobacterial compounds
      produced by Microcystis sp., on aquatic organisms.
AB  - Effects of two cyanobacterial compounds, microcin SF608 and microcystin-LR, were
      investigated on different physiological parameters of two organisms, the water
      moss, Vesicularia dubyana, and the waterflea, Daphnia magna. Both compounds are
      produced by Microcystis species. Microcystin-LR is a potent inhibitor of protein
      phosphatases 1 and 2A, and microcin SF608 inhibits serine proteases. Other
      effects of microcystin-LR are well documented in the literature, but adverse
      effects of microcin SF608 have not been investigated as yet. This study compared
      the effects of both compounds on detoxication enzymes, microsomal and soluble
      glutathione-S-transferase (m-, sGST); oxygen stress enzymes, glutathione
      peroxidase (GP-X), and peroxidase (POD); photosynthetic oxygen production and
      chlorophyll a:chlorophyll b ratio. mGST was inhibited by both compounds in both
      organisms, significantly by microcin SF608, possibly indirectly by inhibition of
      that serine protease transforming the mGST to its active form. The sGST of D.
      magna was inhibited by microcin SF608, but elevated by microcystin-LR, and
      elevated by both compounds in V. dubyana. The GP-X in D. magna was not altered by
      microcin SF608, but elevated parallel to the sGST, whereas the POD in V. dubyana
      was decreased by both. Photosynthetic oxygen production as well as the
      chlorophyll a/b ratio showed typical stress reactions, a decrease of oxygen
      production, and an increase of chlorophyll b, caused both by microcin SF608 and
      by microcystin-LR. Microcin SF608 was not likely to be detoxified via conjugation
      to glutathione. The effects of microcin SF608 and microcystin-LR demonstrate that
      the impact of cyanobacteria on other organisms may not only be directly related
      to the presently known toxins.

PMID- 12203964
TI  - Possible allelopathic effects of cyanotoxins, with reference to microcystin-LR,
      in aquatic ecosystems.
AB  - During recent years a shift from macrophyte-dominated to more phytoplankton
      dominated lakes has been correlated to the process of eutrophication. The
      existence of numerous substances exhibiting allelopathic effects on the growth of
      algae has been shown in different aquatic macrophytes (e.g., Myriophyllum
      spicatum) and is thought to be an important mechanism in stabilizing the
      macrophyte-dominated clear-water state of a lake. A few recent studies have shown
      that algae themselves can produce special substances inhibiting growth or
      photosynthetic processes in other algae. A well-known cyanobacterial secondary
      metabolite, microcystin-LR, was tested for its allelopathic power on aquatic
      macrophytes such as Ceratophyllum demersum and Myriophyllum spicatum, resulting
      in growth inhibition, reduction in photosynthetic oxygen production, and changes
      in pigment pattern. This shows that microcystin-LR has a possible role as an
      allelopathic infochemical.

PMID- 12203967
TI  - Folding and activity of the hammerhead ribozyme.
AB  - The hammerhead is the smallest of the nucleolytic ribozymes, that undergo
      backbone cleavage by a transesterification reaction in the presence of magnesium
      ions. The RNA is induced to fold into its active conformation by the binding of
      metal ions in two stages. These generate domain 2, the scaffold on which the
      ribozyme is built, and domain 1, the active centre of the ribozyme. Further local
      structural rearrangement during the activation of the ribozyme is suggested by a
      number of crystal structures. The 10(5)-fold rate enhancement is probably brought
      about by a combination of metal-ion participation and stereochemical factors in
      the environment of the folded RNA structure.

PMID- 12203968
TI  - Substrate arrays as enzyme fingerprinting tools.

PMID- 12203969
TI  - Selenocysteine derivatives for chemoselective ligations.

PMID- 12203970
TI  - Prion-protein-specific aptamer reduces PrPSc formation.
AB  - The critical initial event in the pathophysiology of transmissible spongiform
      encephalopathies (TSEs) appears to be the conversion of the cellular prion
      protein (PrP(C)) into the abnormal isoform PrP(Sc). This isoform forms high
      molecular-weight protease K (PK) resistant aggregates that accumulate in the
      central nervous system of affected individuals. We have selected nuclease
      resistant 2'-amino-2'-deoxypyrimidine-modified RNA aptamers which recognize a
      peptide comprising amino acid residues 90-129 of the human prion protein with
      high specificity. This domain of prion proteins is thought to be functionally
      important for the conversion of PrP(C) into its pathogenic isoform PrP(Sc) and is
      highly homologous among prion proteins of various species including mouse,
      hamster, and man. Consequently, aptamer DP7 binds to the full-length human,
      mouse, and hamster prion protein. At low concentrations in the growth medium of
      persistently prion-infected neuroblastoma cells, aptamer DP7 significantly
      reduced the relative proportion of de novo synthesized PK-resistant PrP(Sc)
      within only 16 h. These findings may open the door towards a rational development
      of a new class of drugs for the therapy or prophylaxis of prion diseases.

PMID- 12203971
TI  - The impact of R53C mutation on the three-dimensional structure, stability, and
      DNA-binding properties of the human Hesx-1 homeodomain.
AB  - Septo-optic dysplasia (SOD) is loosely defined as any combination of optic nerve
      hypoplasia, pituitary gland hypoplasia, and midline abnormalities of the brain.
      Recent studies have shown that this rare disease has its origin in key mutations
      in Hesx-1, a protein that plays a critical role in normal development of the
      forebrain, eyes, and other anterior structures during embryogenesis. R53C
      mutation in the Hesx-1 homeodomain has recently been identified in some patients
      with SOD. However, no detailed description of the effect of this mutation on the
      protein structure, stability, and function has been reported so far. The impact
      of R53C substitution on Hesx-1 homeodomain structure, stability, and DNA-binding
      properties was analyzed by using a combination of NMR spectroscopy, molecular
      modeling and circular dichroism experiments. Although R53C mutation has very
      slight effects on protein structure, it has a profound impact on homeodomain
      stability. We show that intramolecular disulfide formation can be easily
      accomplished in the mutated homeodomain, which suggests that such bond formation
      could take place in vivo. This modification has a key effect on the homeodomain
      structure and stability, mainly through its effect on helix I/helix III packing.
      Finally, CD titrations allowed us to establish the energy cost of the R53C
      substitution with respect to Hesx-1-homeodomain-DNA complex stability. Detailed
      structural models are provided for the wild-type human Hesx-1 homeodomain and the
      R53C mutant, which is associated with SOD in humans. The reported effect of R53C
      mutation on protein stability and DNA-binding properties, together with the
      significant structural perturbations induced by disulfide formation in the
      mutated polypeptide might explain the loss of activity of the mutant in vivo.

PMID- 12203972
TI  - Multifunctional folded polypeptides from peptide synthesis and site-selective
      self-functionalization--practical scaffolds in aqueous solution.
AB  - The site selectivity of His-mediated lysine and ornithine side-chain acylation in
      a designed four-helix bundle protein scaffold was mapped by reaction of several
      polypeptides with one equivalent of mono-p-nitrophenyl fumarate in aqueous
      solution at pH 5.9 and room temperature followed by an analysis of the degrees
      and sites of acylation. Integration of the HPLC chromatograms of the acylated
      polypeptides and trypsin cleavage followed by mass spectrometry analysis of the
      tryptic fragments provided the experimental evidence. Based on these and
      previously published results a strategy was developed for the site-selective and
      stepwise incorporation of three residues into a folded polypeptide in aqueous
      solution at room temperature. The first substituent was incorporated by reaction
      of a 1.7-fold excess of the corresponding active ester with the polypeptide at pH
      5.9, the second substituent was introduced in a 3-fold excess after the pH value
      was raised to 8, and the third substituent was incorporated by reaction of a 10
      fold excess with the polypeptide at pH 5.9. No intermediate steps of purification
      were taken and the overall yield was 30 % or more. Examples of the substituents
      included are carbohydrates, an enzyme inhibitor, a fumarate, and an acetate
      group. The introduction of different substituents into three individually
      addressable positions in a stepwise, efficient, and controllable reaction
      demonstrates that designed folded polypeptides are practically useful scaffolds
      that can be functionalized by using very simple chemistry in aqueous solution.
      Predicted applications include designed receptors, biosensors, and molecular
      devices.

PMID- 12203973
TI  - Natural deuterium distribution in fatty acids isolated from peanut seed oil: a
      site-specific study by quantitative 2H NMR spectroscopy.
AB  - Quantitative (2)H NMR spectroscopy has been used to measure the distribution of
      deuterium at natural abundance in long-chain fatty acids extracted from the same
      vegetable oil. Peanut seed oil was selected, due to its suitable oleic and
      linoleic acid content. The methyl esters of the fatty acids were prepared by
      transesterification and isolated by modified argentation column chromatography on
      silica. In order to measure the natural isotopic fractionation of deuterium (D)
      at the maximum number of positions, the purified methyl oleate and methyl
      linoleate were chemically cleaved and the (D/H)(i) values determined by
      quantitative (2)H NMR spectroscopy. It was thus possible to demonstrate that
      fractionation in deuterium occurs during the desaturation of oleate to linoleate.
      Furthermore, the previously observed distribution of deuterium at the sites of
      desaturation is confirmed, as is the alternating pattern of (D/H)(i), which
      relates to the origin of the pertinent hydrogen atoms. The data obtained are
      discussed in terms of the kinetic isotopic effects intrinsic to the enzymes
      synthetases and desaturases-involved in the biosynthesis of fatty acids.

PMID- 12203974
TI  - Determination of the carbon kinetic isotope effects on propane hydroxylation
      mediated by the methane monooxygenases from Methylococcus capsulatus (Bath) by
      using stable carbon isotopic analysis.
AB  - Authentic propane with known position-specific carbon isotope composition at each
      carbon atom was subjected to hydroxylation by the particulate and soluble methane
      monooxygenase (pMMO and sMMO) from Methylococcus capsulatus (Bath), and the
      corresponding position-specific carbon isotope content was redetermined for the
      product 2-propanol. Neither the reaction mediated by pMMO nor that with sMMO
      showed an intermolecular (12)C/(13)C kinetic isotope effect effect on the propane
      hydroxylation at the secondary carbon; this indicates that there is little
      structural change at the carbon center attacked during formation of the
      transition state in the rate-determining step. This finding is in line with the
      concerted mechanism proposed for pMMO (Bath), and suggested for sMMO (Bath),
      namely, direct side-on insertion of an active "O" species across the C-H bond, as
      has been previously reported for singlet carbene insertion.

PMID- 12203975
TI  - Eilatin Ru(II) complexes display anti-HIV activity and enantiomeric diversity in
      the binding of RNA.
AB  - Eilatin-containing octahedral ruthenium complexes inhibit HIV-1 replication in
      CD4+ HeLa cells and in human peripheral blood monocytes with IC(50) values of
      approximately 1 microM. Similar metal complexes that lack eilatin display 15-100
      fold lower anti-HIV activities. [Ru(bpy)(2)"pre-eilatin"](2+), a complex that
      contains a nonplanar analogue of eilatin, shows significantly lower nucleic acid
      binding and lower anti-HIV activity than eilatin complexes. This result indicates
      that the extended planar surface presented by eilatin is important for both
      activities. Rev peptide and ethidium bromide displacement assays are used to
      probe the nucleic acid affinity and specificity of Lambda- and Delta
      [Ru(bpy)(2)eilatin](2+). Two HIV-1 RNA sites are compared and a significant
      binding preference for the Rev response element over the transactivation response
      region is found. Simple DNA duplexes show a consistent selectivity for Lambda
      [Ru(bpy)(2)eilatin](2+) compared to Delta-[Ru(bpy)(2)eilatin](2+), while RNAs
      show more diverse enantiomeric selectivities.

PMID- 12203976
TI  - Discovery of potent inhibitors of PapG adhesins from uropathogenic Escherichia
      coli through synthesis and evaluation of galabiose derivatives.
AB  - The synthesis of two galabioside (Galalpha1-4Gal) collections based on
      diversification at the O-1 and O-3' atoms is reported. The galabiosides were
      evaluated as inhibitors of hemagglutination of human erythrocytes by two strains
      of Escherichia coli that expressed the class I and class II PapG adhesins,
      respectively. The class I adhesin was found to prefer aromatic substituents both
      at the O-1 and the O-3' position of the galabiose disaccharide. One galabioside,
      p-methoxyphenyl [3-O-(m-nitrobenzyl)-alpha-D-galactopyranosyl]-(1-4)-beta-D
      galactopyranoside], had an IC(50) value of 4.1 microM, which is the best
      inhibition of the class I adhesin to date. In the case of the class II adhesin,
      one inhibitor, 2-[(S)-2-methoxycarbonyl-2-acetamido-ethylthio]ethyl (3-O-3-[2
      (methoxycarbonylphenylthio)propyl]-alpha-D-galactopyranosyl)-(1-4)-alpha-D
      galactopyranoside, was found to have an IC(50) value of 68 microM, which is the
      best artificial inhibition of the class II adhesin reported so far with an
      affinity for the adhesin comparable to that of the natural tetrasaccharide ligand
      globotetraose.

PMID- 12203977
TI  - Modification of galactose oxidase to introduce glucose 6-oxidase activity.

PMID- 12203978
TI  - A receptor-targeted near-infrared fluorescence probe for in vivo tumor imaging.

PMID- 12203979
TI  - Photoregulation of the transcription reaction of T7 RNA polymerase by tethering
      an azobenzene to the promoter.

PMID- 12203980
TI  - Site-directed mutagenesis of Tyr354 in Geobacillus stearothermophilus alanine
      racemase identifies a role in controlling substrate specificity and a possible
      role in the evolution of antibiotic resistance.

PMID- 12203981
TI  - Bioorganic chemistry meeting in Wales.

PMID- 12203987
TI  - Mutations of FBN1 and genotype-phenotype correlations in Marfan syndrome and
      related fibrillinopathies.
AB  - The Marfan syndrome (MFS) is a pleiotropic, autosomal dominant disorder of
      connective tissue with highly variable clinical manifestations including aortic
      dilatation and dissection, ectopia lentis, and a series of skeletal anomalies.
      Mutations in the gene for fibrillin-1 (FBN1) cause MFS, and at least 337 mainly
      unique mutations have been published to date. FBN1 mutations have been found not
      only in MFS but also in a range of connective tissue disorders collectively
      termed fibrillinopathies ranging from mild phenotypes, such as isolated ectopia
      lentis, to severe disorders including neonatal MFS, which generally leads to
      death within the first two years of life. The present article intends to provide
      an overview of mutations found in MFS and related disorders and to discuss
      potential genotype-phenotype correlations in MFS.

PMID- 12203988
TI  - Data mining of public SNP databases for the selection of intragenic SNPs.
AB  - Different strategies to search public single nucleotide polymorphism (SNP)
      databases for intragenic SNPs were evaluated. First, we assembled a strategy to
      annotate SNPs onto candidate genes based on a BLAST search of public SNP
      databases (Intragenic SNP Annotation by BLAST, ISAB). Only BLAST hits that
      complied with stringent criteria according to 1) percentage identity (minimum
      98%), 2) BLAST hit length (the hit covers at least 98% of the length of the SNP
      entry in the database, or the hit is longer than 250 base pairs), and 3) location
      in non-repetitive DNA, were considered as valid SNPs. We assessed the intragenic
      context and redundancy of these SNPs, and demonstrated that the SNP content of
      the dbSNP and HGBASE/HGVbase databases are highly complementary but also overlap
      significantly. Second, we assessed the validity of intragenic SNP annotation
      available on the dbSNP and HGVbase websites by comparison with the results of the
      ISAB strategy. Only a minority of all annotated SNPs was found in common between
      the respective public SNP database websites and the ISAB annotation strategy. A
      detailed analysis was performed aiming to explain this discrepancy. As a
      conclusion, we recommend the application of an independent strategy (such as
      ISAB) to annotate intragenic SNPs, complementary to the annotation provided at
      the dbSNP and HGVbase websites. Such an approach might be useful in the selection
      process of intragenic SNPs for genotyping in genetic studies. Hum Mutat 20:162
      173, 2002.

PMID- 12203989
TI  - SNP databases and pharmacogenetics: great start, but a long way to go.
AB  - With the recent publication of the human genome project there has been an
      explosion of data available for pharmacogenetic research. Web-based databases
      containing information on single nucleotide polymorphisms (SNPs) are readily
      accessible to researchers, but there has been little comment on their utility. We
      used seven major international databases to identify SNPs in 74 genes involved in
      drug pathways. Very little overlap was seen among the databases, with only eight
      out of a putative 893 SNPs ( approximately 1%) common to the most commonly used
      databases. Problems with false positives, secondary to a high degree of homology
      in gene families, were also observed. These studies suggest researchers limiting
      their studies to one database would miss a great deal of information. Effort to
      update compilation databases, such as HGVbase, GeneSNP, PharmGKB, and HOWDY, and
      the aggressive removal of false positives from all databases is required if these
      resources are to facilitate the intended growth in pharmacogenetics research.

PMID- 12203990
TI  - Splicing mutations, mainly IVS6-1(G>T), account for 70% of fumarylacetoacetate
      hydrolase (FAH) gene alterations, including 7 novel mutations, in a survey of 29
      tyrosinemia type I patients.
AB  - Hereditary tyrosinemia type I (HTI) is an autosomal recessive disease
      characterized by a deficiency in fumarylacetoacetate hydrolase (FAH) activity. In
      this work, the FAH genotype was established in a group of 29 HTI patients, most
      of them from the Mediterranean area. We identified seven novel mutations-IVS8
      1(G>A, IVS10-2(A>T), 938delC, E6/I6del26, W78X, Q328X, and G343W-and two
      previously described mutations-IVS6-1(G>T) and IVS12+5(G>A). Fully 92.8% of the
      patients were carriers of at least one splice site mutation, with IVS6-1(G>T)
      accounting for 58.9% of the total number of alleles. The splice mutation group of
      patients showed heterogeneous phenotypic patterns ranging from acute forms with
      severe liver malfunction to chronic forms with renal manifestations and slow
      progressive hepatic alterations. Qualitative FAH cDNA expression was the same in
      all IVS6-1(G>T) homozygous patients regardless of their clinical picture. One
      patient with a heterozygous combination of a nonsense (Q328X) and a frameshift
      (938delC) mutation showed an atypical clinical picture of hypotonia and repeated
      infections. Despite the high prevalence of IVS12+5(G>A) in the northwestern
      European population, we found only two patients with this mutation in our group.

PMID- 12203991
TI  - Mutational analysis of patients with the diagnosis of choroideremia.
AB  - All reported mutations in the choroideremia (CHM) gene result in the truncation
      or complete absence of Rab escort protein 1 (REP1). Molecular analysis was
      carried out on 57 families diagnosed with CHM. Confirmation of the clinical
      diagnosis is important as end-stage CHM may be clinically similar to the end
      stages of other retinal degenerative diseases such as RP. The primary means of
      confirming the diagnosis of CHM is to sequence all 15 exons. An alternative
      method involves detection of the REP1 protein, as described in MacDonald et al.
      [1998]. A monoclonal antibody to REP1 does not detect truncated REP1 by
      immunoblot analysis, presumably due to instability and subsequent degradation of
      the truncated protein. This analysis provides relatively fast confirmation of the
      diagnosis, however, protein samples are not always available and are susceptible
      to degradation, affecting the accurate interpretation of results. CHM gene
      mutations were found in 54 of 57 families studied. The majority of mutations
      (>42%) were transitions and transversions. Complete deletions of the CHM gene and
      deletion/insertion mutations each accounted for almost 4% of the total, while
      over 9% had large intragenic and other partial deletions. Almost 28% of the
      mutations were deletions of fewer than 5 base pairs (bp) and almost 13% were
      splice site mutations. Despite the fact that mutations are found throughout the
      gene with no common mutation for the disorder, identical mutations have been
      characterized in unrelated individuals. The majority of these mutations are C to
      T transitions, changing an arginine residue (CGA) to a stop codon (TGA). Four of
      the five CGA codons in the CHM gene are sites of recurring mutations.

PMID- 12203992
TI  - TGGE screening of the entire FBN1 coding sequence in 126 individuals with marfan
      syndrome and related fibrillinopathies.
AB  - Mutations in the gene for fibrillin-1 (FBN1) cause Marfan syndrome (MFS), an
      autosomal dominant heritable disorder of connective tissue with prominent
      manifestations in the skeletal, ocular, and cardiovascular system. FBN1 mutations
      have also been identified in a series of related disorders of connective tissue
      collectively termed type-1 fibrillinopathies. We have developed temperature
      gradient gel electrophoresis (TGGE) assays for all 65 FBN1 exons, screened 126
      individuals with MFS, other type-1 fibrillinopathies, and other potentially
      related disorders of connective tissue for FBN1 mutations, and identified a total
      of 53 mutations, of which 33 are described here for the first time. Several
      mutations were identified in individuals with fibrillinopathies other than
      classic Marfan syndrome, including aneurysm of the ascending aorta with only
      minor skeletal anomalies, and several individuals with only skeletal and ocular
      involvement. The mutation detection rate in this study was 42% overall, but was
      only 12% in individuals not fulfilling the diagnostic criteria for MFS,
      suggesting that clinical overdiagnosis is one reason for the low detection rate
      observed for FBN1 mutation analysis.

PMID- 12203993
TI  - Population genetic implications from DNA polymorphism in random human genomic
      sequences.
AB  - Denaturing high performance liquid chromatography (DHPLC) in combination with dye
      terminator sequencing was used to survey 516 random genomic sequence tagged sites
      (STSs) for biallelic polymorphisms in 24 representatives of the major ethnic
      groups residing in the United States. Of the 301 polymorphic STSs (58.3%), 172
      contained a single simple sequence polymorphism (SSP), while 78, 35, and 16
      contained 2, 3, and 4-6 SSPs, respectively. Of the 541 SSPs identified, 342
      (63%), 152 (28%), and 47 (9%) were transitions, transversions, and insertions or
      deletions, respectively. Only 21% of the STSs contained SSPs with a minor-allele
      frequency >20%. The nucleotide diversity estimate for random genomic sequences
      theta = 8.23 x 10(-4) was on average 50% higher than that for intragenic non
      coding regions of the human genome ( theta = 5.52 x 10(-4). The discrepancy in
      Tajima's D statistic between 22 autosomal genes (D=-1.304+/-0.622, mean+/-SD) and
      random STSs (D=-0.27) suggests that, in the absence of significant mutation rate
      heterogeneity, the more negative values for genes are a consequence of
      directional selection rather than population growth.

PMID- 12203994
TI  - Rapid detection of novel BRCA1 rearrangements in high-risk breast-ovarian cancer
      families using multiplex PCR of short fluorescent fragments.
AB  - Recent studies have revealed a significant proportion of BRCA1 exon deletions or
      duplications in breast-ovarian cancer families with high probability of BRCA1- or
      BRCA2-linked predisposition, in which mutations of these genes have not been
      found. The difficulty of detecting such heterozygous rearrangements has
      stimulated the development of several new screening methods. Quantitative
      fluorescent multiplex PCR is based on simultaneous amplification of multiple
      target sequences under conditions that allow rapid and reliable quantitative
      comparison of the fluorescence of each amplicon in test samples and in controls.
      The modified method described here, named quantitative multiplex PCR of short
      fluorescent fragments (QMPSF), is particularly well suited for large genes. All
      BRCA1 coding exons were analyzed using four multiplexes in 52 families without
      point mutations in the exons or splice-sites of BRCA1 and BRCA2, and selected
      because of high probability of a BRCA1- or BRCA2-linked genetic predisposition.
      Five distinct BRCA1 rearrangements were detected: a deletion of exons 8-13, a
      duplication of exons 3-8, a duplication of exons 18-20, a deletion of exons 15
      16, and a deletion of exons 1-22-which is the largest deletion found so far
      within the BRCA1 gene. The method described here lends itself to rapid,
      sensitive, and cost-effective search of BRCA1 rearrangements and may be included
      into the routine molecular analysis of breast-ovarian cancer predispositions. Hum
      Mutat 20:218-226, 2002.

PMID- 12203995
TI  - Third international meeting on the genetic epidemiology of complex traits, April
      4-6, 2002, Cambridge, UK.
AB  - The Third International Meeting on the Genetic Epidemiology of Complex Traits was
      held at Churchill College, Cambridge, UK on April 4-6, 2002. The event was
      organized by the Twin Research and Genetic Epidemiology Unit, St Thomas'
      Hospital, London and sponsored by Roche Genetics and Insightful. It provided an
      interactive forum for discussion of topical issues relating to the genetic
      analysis of complex diseases and traits. Topics discussed included linkage
      disequilibrium mapping and candidate gene analysis, as well as cutting edge
      advances in both technologies and statistical analysis methods. Details of the
      meeting can be found at http://www.twin-research.ac.uk/.

PMID- 12203996
TI  - Large Family With Maturity-Onset Diabetes of the Young and a Novel V121I Mutation
      in HNF4A.
AB  - Maturity-onset diabetes of the young (MODY) is a subtype of early-onset diabetes
      mellitus which is characterized by autosomal dominant inheritance. Several genes
      are known to induce MODY : HNF4A/MODY1, GCK/MODY2, TCF1/MODY3, IPF1/MODY4,
      TCF2/MODY5 and NEUROD1/MODY6. We studied a Swiss family with 13 diabetic patients
      over 3 generations. The average age at diagnosis was 35 +/- 15 years (7 subjects
      before 30). In addition, 2 individuals had an abnormal oral glucose tolerance.
      The mutation present in this family was located in the DNA binding domain of
      HNF4A, a strongly conserved region across almost all species, and segregated in
      all the MODY patients. Identification of this missense mutation allowed for
      presymptomatic diagnosis in the younger generations and will improve medical
      follow-up of the predisposed individuals.

PMID- 12203997
TI  - Analysis of breast cancer susceptibility genes BRCA1 and BRCA2 in Thai familial
      and isolated early-onset breast and ovarian cancer.
AB  - Here we report the study on BRCA1 and BRCA2 mutations in 12 Thai breast and/or
      ovarian cancer families and 6 early-onset breast or breast/ovarian cancer cases
      without a family history of cancer. Five distinct rare alterations were
      identified in each gene: four introducing premature stop codons, one in-frame
      deletion, two missense changes, two intronic alterations and one silent rare
      variant. The BRCA1 or BRCA2 truncating mutations were detected in four of seven
      patients with familial or personal history of breast and ovarian cancer, in one
      of four isolated early onset breast cancer cases and in none of seven breast
      cancer site specific families. The BRCA1 and BRCA2 mutation yield in Thai
      patients is consistent with that reported from Europe and North America in
      similar groups of patients, being particularly high in individuals with personal
      or family history of breast and ovarian cancer. The BRCA1 and BRCA2 alterations
      found in this series are different from those identified in other Asian studies,
      and all but two have never been reported before. We report at least three novel
      deleterious mutations, the BRCA1 3300delA, BRCA1 744ins20 and BRCA2 6382delT. One
      in-frame deletion was also found, the BRCA2 5527del9, which seggregated within
      family members of breast-only cancer patients and was thought to be a cancer
      related mutation. BRCA1 3300delA and Asp67Glu alterations were detected each in
      at least two families and thus could represent founder mutations in Thais.

PMID- 12203998
TI  - Identification of seven novel mutations of F8C by DHPLC.
AB  - Hemophilia A is an X-linked recessive disorder resulting from deficiency of
      Factor VIII (F8C), an important protein in blood coagulation. A large number of
      disease producing mutations have been reported in the F8C gene. However, a
      comprehensive analysis of mutations is difficult to conduct due to the large gene
      size, its many scattered exons, and the high frequency of de novo mutations. In
      this study, we performed analysis using PCR, Conformation Sensitive Gel
      Electrophoresis (CSGE), Denaturing High Performance Liquid Chromatography (DHPLC)
      and direct sequencing. We found seven novel mutations causing severe, moderate
      and mild Hemophilia A: IVS14-1G>A, G458V, T1695S, L1758P, Q2311P, 1441delT, 1269
      1271insA. At least four variants detected by DHPLC (IVS14-1G>A, Q2311P,_R698W and
      D1241Q) were not detectable by CSGE.

PMID- 12203999
TI  - Molecular analysis of 30 mucopolysaccharidosis type I patients: evaluation of the
      mutational spectrum in Italian population and identification of 13 novel
      mutations.
AB  - Mucopolysaccharidosis type I (MPS-I orMPS1) is an autosomal recessive condition
      characterized by a broad range of clinical symptoms. Molecular diagnosis of MPS-I
      is important for analyzing genotype-phenotype correlation and for selecting
      patients for innovative therapies. In this study we analyzed 30 Italian MPS-I
      patients with different phenotypes (20 severe, 6 intermediate, 4 mild) in an
      attempt to recognize the mutational spectrum in our population and to identify
      major DNA alterations specific to our country. We identified 93% of mutated
      alleles (56 out of 60) with the reconstruction of the complete genotype in 26
      patients out of 30. Twenty-three different mutations were found, 13 of which are
      novel while the remaining 10 have been already described. Among the novel
      mutations we found 5 non conservative missense mutations (A160D, E178K, P183R,
      G197D, D349Y), one nonsense mutation (C53X), 6 deletions (468-470del3, 486
      491del6, 755-759del5, 1251delC, 1839-1867del29, 1902-1903del2), and one splice
      site mutation (IVS11+5G>A). No common mutation for MPS-I is present in our
      country. Frequently (40% of the alleles), mutations were found in just one or two
      patients. However, Q70X, P533R, G51D, and W402X mutations were present in several
      patients (15%, 13.3%, 13.3%, and 11.6% of the alleles respectively) suggesting a
      Mediterranean origin of the P533R and G51D mutations. In most cases the patients'
      genotypes were unique combinations of mutations. The great heterogeneity found in
      our MPS-I population hampers mutation detection and hinders the genotype
      phenotype correlation.

PMID- 12204000
TI  - A founder mutation (R254X) of SLC22A5 (OCTN2) in Chinese primary carnitine
      deficiency patients.
AB  - Mutations in the SLC22A5 gene, which encodes for the plasma membrane carnitine
      transporter OCTN2, cause primary carnitine deficiency (PCD). After our first
      report of OCTN2 mutations in Chinese, three more Chinese PCD patients were
      identified. The parents of these families were non-consanguineous and these
      families were unrelated. Two novel truncating mutations were found: R254X, a
      single-base mutation at cDNA position 981 (c.981C>T); and Y387X (c.1382T>G). Two
      probands, one each from Taiwan and Macau, were homozygous for R254X. The other
      proband from Taiwan carried both R254X and Y387X. Two additional heterozygote
      carriers of R254X were also identified among 250 control samples, while none was
      detected for Y387X. The population carrier rate for R254X would be about 1 in
      125. Haplotypes of R254X alleles were examined and patients homozygous for R254X
      were also homozygous for the same haplotype of intragenic and microsatellites
      markers. Analysis of population frequencies of haplotypes revealed that the
      chance of 4 chromosomes having arisen as independent events was 0.016. We
      conclude that R254X is probably a founder mutation in Chinese. Other previously
      reported mutations found in the Japanese population were also screening in 250
      control samples but no carrier was identified, indicating that they were either
      very rare or not present in Southern Chinese.

PMID- 12204001
TI  - Genotype-phenotype studies of six novel LPL mutations in Chinese patients with
      hypertriglyceridemia.
AB  - We screened 160 unrelated Chinese hypertriglyceridemic subjects for sequence
      alterations in the promoter and the 10 exons of the lipoprotein lipase (LPL)
      gene. We identified one reported mutation (L252R), one common polymorphism
      (S447X), and six novel mutations: V181I, C283Y, S298R and S338F (found in single
      individuals), L252V (in two individuals), and A71T (in three individuals).
      Screening of family members of the above probands revealed a total of 19 mutation
      carriers, most of whom, though not all, displayed reduced LPL activity and mass
      when compared to normolipidemic control subjects. In in vitro expression studies,
      A71T, V181I, L252R, L252V and C283Y decreased the specific activity of the gene
      product. Interestingly, S298R had no effect on the catalytic activity while S338F
      increased it. A71T and C283Y reduced the secretion of the mutant proteins
      significantly while V181I, S298R and S338F had mild effects only. The total LPL
      mass of all the mutant constructs was reduced compared to that of the wild type
      construct, probably due to the instabilities of the mutant mRNA or the mutant
      protein. The heterogeneity in phenotypic effects of these mutations is a likely
      consequence of their variable effects on proteoglycan binding, conformation and
      interactions with other secondary genetic or environmental factors.

PMID- 12204002
TI  - Genetic background of Huntington disease in Croatia: Molecular analysis of CAG,
      CCG, and Delta2642 (E2642del) polymorphisms.
AB  - This study presents the first molecular data on the basis and the origin of
      Huntington disease in Croatia and is the first such analysis performed among a
      Slavic population. We analyzed three trinucleotide polymorphisms in the HD gene:
      CAG, CCG and GAG Delta2642 (E2642del) triplets. Analysis of the CAG repeat size
      among 44 Huntington patients (39-66 CAGs) and 51 normal individuals (9-34 CAGs)
      showed that the range of the repeats was similar to previous findings. The
      frequency of the CCG and Delta2642 polymorphic alleles on N and HD chromosomes
      was found to correlate well with earlier reports for Western European
      populations. We found significance for both the CCG7 allele (p=0.004) and the
      Delta2642 allele (p<0.001) among HD chromosomes. The CCG7 allele was
      overpresented among affected chromosomes (94.6%), but was also the most frequent
      CCG allele among normal chromosomes (66.7%). Interestingly, the Delta2642 allele
      was present on 40.5% HD chromosomes compared to only 9.8% of control chromosomes.
      Our results indicate that HD mutations in Croatia could be of the same origin as
      in Western populations and also support the multi-step hypothesis for generating
      new HD alleles. Similar frequencies and distributions of both the CCG and the
      Delta2642 polymorphisms in Croatia and Western European normal chromosomes
      indicate that the prevalence rate of HD in Croatia may be as high as in Western
      populations. Since we estimated a lower prevalence rate (1 : 100,000), we assume
      that there are still many misdiagnosed and/or unrecognized cases of Huntington
      disease in Croatia.

PMID- 12204003
TI  - Analysis of the PTCH coding region in human rhabdomyosarcoma.
AB  - Inherited mutations of the human tumor suppressor gene Patched (PTCH) lead to an
      autosomal dominant disorder known as Nevoid Basal Cell Carcinoma Syndrome
      (NBCCS). The syndrome is characterized by a combination of developmental
      abnormalities and a predisposition to tumor formation. Tumors in patients with
      NBCCS include basal cell carcinoma, medulloblastoma, fibroma and rhabdomyosarcoma
      (RMS). RMS are also present in 15 % of mice haplodeficient for Ptch. To
      investigate whether mutations in PTCH are a general feature in
      rhabdomyosarcomagenesis we sequenced the protein-coding region in sporadic human
      cases of these tumors. For this purpose we first determined the distribution and
      frequency of polymorphisms in 23 exons of PTCH in 48 healthy caucasians. Ten new
      polymorphisms were identified (IVS11 + 15-17del AAA; IVS14 + 25T>C; 2485G>A;
      IVS15 + 9G>C; IVS17 + 21A>G; 3033T>C; 3149T>C; 3387T>C; 3617G>A; 4080C>T). Next,
      the PTCH coding region in 14 RMS was sequenced. Whereas one case with LOH at the
      PTCH locus was detected, none of the cases showed nonsense or missense mutations
      in the coding region of PTCH. These data do not support the existence of frequent
      mutations in the protein-coding region of PTCH in RMS.

PMID- 12204004
TI  - Human piebaldism: six novel mutations of the proto-oncogene KIT.
AB  - Human piebaldism is a rare autosomal dominant disorder that comprises congenital
      patchy depigmentation of the scalp, forehead, trunk and limbs. It is caused by
      mutations in the cell-surface receptor tyrosine kinase gene (KIT, also c-kit). We
      screened three families and three isolated cases of piebaldism from different
      countries for mutations in the KIT gene using automated sequencing methods. We
      report six novel KIT point mutations: three missense (C788R, W835R, P869S) at
      highly conserved amino acid sites; one nonsense (Q347X) that results in
      termination of translation of the KIT gene in exon 6; and two splice site
      nucleotide substitutions (IVS13+2T>G, IVS17-1G>A) that are predicted to impair
      normal splicing. These mutations were not detected in over 100 normal individuals
      and are likely to be the cause of piebaldism in our subjects.

PMID- 12204005
TI  - Analysis of the glucocerebrosidase gene and mutation profile in 144 Italian
      gaucher patients.
AB  - Gaucher disease (GD), the most prevalent lysosomal storage disease characterized
      by a remarkable degree of clinical variability, results from deleterious
      mutations in the glucocerebrosidase gene (GBA). In this paper we report the
      molecular characterization of 144 unrelated Italian GD patients with the three
      types of the disease. The allelic frequencies of Italians are reported and the
      mutation profile is analyzed. Besides the common N370S, L444P, RecNciI, G202R,
      IVS2+1G>A, D409H, F213I mutations, the different molecular strategies, used for
      the mutation detection, identified the rare N107L, R131C, R170C, R170P, N188S,
      S196P, R285C, R285H, W312C, D399N, A446P, IVS10-1G>A, RecDelta55, total gene
      deletion, as well as 12 mutant alleles that were exclusively present in the
      Italian population until now: the previously reported R353G, N370S+S488P
      mosaicism, IVS8(-11delC)-14T>A), Rec I, Y418C, and the seven novel alleles D127X,
      P159T, V214X, T231R, L354X, H451R, and G202R+M361I. The wide phenotypic
      differences observed within the genotypic groups as well as between siblings
      implicate a significant contribution of other modifying genetic and/or non
      genetic factors and claim a comprehensive valuation of the patient including
      clinical., biochemical and molecular investigations for prognosis, appropriate
      interventive therapy and reliable genetic counseling.

PMID- 12204006
TI  - Germline mutations of BRCA1 and BRCA2 in Korean breast and/or ovarian cancer
      families.
AB  - Germline mutations in the BRCA1 and BRCA2 genes are responsible for the
      predisposition and development of familial breast and/or ovarian cancer. Most
      mutations of BRCA1 and BRCA2 associated with breast and/or ovarian cancer result
      in truncated proteins. To investigate the presence of BRCA1 and BRCA2 germline
      mutations in Korean breast and/or ovarian cancer families, we screened a total of
      27 cases from 21 families including two or more affected first- or second-degree
      relatives with breast and/or ovarian cancer. PTT, PCR-SSCP, and DHPLC analysis,
      followed by sequencing were used in the screening process. In nine families, we
      found BRCA1 and BRCA2 germline mutations that comprised four frameshift mutations
      and five nonsense mutations. All nine mutations led to premature termination
      producing shortened proteins. Among the nine mutations, three novel BRCA1
      mutations (E1114X, Q1299X, 4159delGA) and two novel BRCA2 mutations (K467X,
      8945delAA) were identified in this work.

PMID- 12204007
TI  - Identification of mutations of Bruton's tyrosine kinase gene (BTK) in Brazilian
      patients with X-linked agammaglobulinemia.
AB  - Mutations in the Bruton tyrosine kinase (BTK) gene are responsible for X-linked
      agammaglobulinemia (XLA), which is characterized by recurrent bacterial
      infections, profound hypogammaglobulinemia, and decreased numbers of mature B
      cells in the peripheral blood. We evaluated 17 male Brazilian patients from 13
      unrelated families who showed markedly reduced numbers of blood B cells and
      hypogammaglobulinemia. BTK gene analysis detected mutations in 10 of the 13
      presumed XLA families. Seven mutations (Q196X, G613D, R28L, 251-273del, Q234X,
      H364P, and R13X) had been reported previously, whereas the remaining three
      mutations (M501T, IVS15+1G>C, and IVS14+1G>A) were novel. Mutation IVS15+1G>C
      occurred in a splice donor site and caused exons 15 and 16 to be skipped, and
      IVS14+1G>A might cause exon 14 to be skipped. Flow cytometry revealed deficient
      expression of BTK protein in 10 of the 13 families. This is the first report of
      the diagnosis of XLA by analysis of mutations of the BTK gene in Brazilian
      patients.

PMID- 12204008
TI  - Occurrence of deletion of a COL2A1 allele as the mutation in Stickler syndrome
      shows that a collagen type II dosage effect underlies this syndrome.
AB  - We describe a novel type of mutation in the COL2A1 gene in a family with Stickler
      syndrome, namely a deletion of an entire COL2A1 allele. Until now, almost all
      COL2A1 mutations found in this syndrome are nucleotide substitutions, small
      deletions, or insertions, resulting in premature translation termination. Since
      the phenotype in this family is not different from cases with a truncated alpha
      chain, our finding supports the suggestion that a dosage effect is underlying
      Stickler syndrome. Moreover, in mutation screening protocols for COL2A1 one
      should be aware of the possibility of large deletions, which are not detected by
      generally used PCR-based methods.

PMID- 12204009
TI  - Prevalence of small rearrangements in the factor VIII gene F8C among patients
      with severe hemophilia A.
AB  - Hemophilia A is a common X-linked bleeding disorder caused by various types of
      mutations in the factor VIII gene F8C. The most common intron 22-inversion is
      responsible for about 40% of the severe hemophilia A cases while large deletions,
      point mutations and small (less than 100 bp) deletions or insertions are
      responsible for the disease in the rest of patients. We report on nine novel (6
      deletions, two indels and one partial duplication) and five recurrent small
      rearrangements identified in 15 German patients with severe hemophilia A,
      negative for the intron 22-inversion. c.2208-2214delTTATTAC/c.2207-2215insCTCTT
      and c.4665-4678del/c.4664-4678insAAGGAA identified in the present study are the
      first small indels described in the factor VIII gene. Our analyses suggest that
      the prevalence of this type of mutations (predominantly located in exon 14) among
      patients with severe phenotype and negative for the common intron 22-inversion,
      is about 30%. The correlation between these molecular defects and formation of
      factor VIII inhibitors as well as the parental origin of the de novo mutations
      are evaluated. Finally we show that denaturing HPLC (DHPLC) and classic
      heteroduplex analysis (HA) are able to detect these sequence alterations on 100%
      and could be preferred as a screening approach when analysing for mutations in
      factor VIII in severely affected patients.

PMID- 12204010
TI  - Analysis of the CTNS gene in patients of German and Swiss origin with
      nephropathic cystinosis.
AB  - The autosomal recessive lysosomal storage disorder, nephropathic cystinosis is
      characterized by impaired transport of free cystine out of lysosomes. The gene
      responsible for cystinosis, CTNS, consists of 12 exons and encodes a 55 kDa
      putative lysosomal membrane protein, called cystinosin. Up to now more than 55
      different CTNS mutations have been described in cystinosis. We have analyzed the
      mutation pattern in a population of 40 cystinosis patients from 35 families of
      German and Swiss origin. CTNS mutations in 68 out of 70 alleles were identified.
      The common 57-kb deletion accounted for 65% of the alleles. In five patients we
      found a known GACT deletion at position 18-21. In two patients we identified a
      nucleotide substitution at codon 339 and one patient showed a CG insertion at
      position 697-698. In five patients we observed a G insertion at position 926-927.
      Moreover, five novel mutations including two deletions involving exon 3 (61
      61+2delGGT) and exon 6 (280delG), two insertions in exon 6 (292-293insA) and exon
      7 (684insCACTT) and one nucleotide substitution in exon 11 (923G>T) have been
      identified. These data provide a basis for routine molecular diagnosis of
      cystinosis in the central European population, especially in cystinosis patients
      of German and Swiss origin.

PMID- 12204013
TI  - The Canadian National Breast Screening Study-1: breast cancer mortality after 11
      to 16 years of follow-up. A randomized screening trial of mammography in women
      age 40 to 49 years.
AB  - BACKGROUND: The efficacy of breast cancer screening in women age 40 to 49 years
      remains controversial. OBJECTIVE: To compare breast cancer mortality in 40- to 49
      year-old women who received either 1) screening with annual mammography, breast
      physical examination, and instruction on breast self-examination on 4 or 5
      occasions or 2) community care after a single breast physical examination and
      instruction on breast self-examination. DESIGN: Individually randomized,
      controlled trial. SETTING: 15 Canadian centers. PARTICIPANTS: 50 430 volunteers
      age 40 to 49 years, recruited from January 1980 to March 1985, who were not
      pregnant, had no previous breast cancer diagnosis, and had not had mammography in
      the preceding 12 months. INTERVENTIONS: Breast physical examination and
      instruction on breast self-examination preceded random assignment of 25 214 women
      to receive mammography and annual mammography, breast physical examination, and
      breast self-examination and 25 216 women to receive usual community care with
      annual follow-up. MEASUREMENTS: Verified breast cancer incidence and cohort
      mortality through 31 December 1993 and deaths from breast cancer through 30 June
      1996. RESULTS: The 105 breast cancer deaths in the mammography group and 108
      breast cancer deaths in the usual care group yielded a cumulative rate ratio,
      adjusted for mammography done outside the study, of 1.06 (95% CI, 0.80 to 1.40).
      A total of 592 cases of invasive breast cancer and 71 cases of in situ breast
      cancer were diagnosed by 31 December 1993 in the mammography group compared with
      552 and 29 cases, respectively, in the usual care group. The expected proportions
      of nonpalpable and small invasive tumors were detected on mammography.
      CONCLUSION: After 11 to 16 years of follow-up, four or five annual screenings
      with mammography, breast physical examination, and breast self-examination had
      not reduced breast cancer mortality compared with usual community care after a
      single breast physical examination and instruction on breast self-examination.
      The study data show that true effects of 20% or greater are unlikely.

PMID- 12204014
TI  - Relationship of antihypertensive treatment regimens and change in blood pressure
      to risk for heart failure in hypertensive patients randomly assigned to doxazosin
      or chlorthalidone: further analyses from the Antihypertensive and Lipid-Lowering
      treatment to prevent Heart Attack Trial.
AB  - BACKGROUND: The Antihypertensive and Lipid-Lowering treatment to prevent Heart
      Attack Trial reported that treatment initiated with doxazosin compared with
      chlorthalidone doubled the risk for heart failure in high-risk hypertensive
      patients (relative risk, 2.04 [95% CI, 1.79 to 2.32]). Patients assigned to
      doxazosin therapy had a mean in-trial systolic/diastolic blood pressure 3/0 mm Hg
      higher than that in patients assigned to chlorthalidone. Sixty-eight percent
      (6167 of 9061) of the former patients and 59% (9081 of 15 256) of the latter
      patients were given additional medications to achieve a target blood pressure of
      less than 140/90 mm Hg. OBJECTIVE: To ascertain the influence of open-label
      antihypertensive drugs and subsequent blood pressure on relative risk for heart
      failure. DESIGN: Randomized, double-blind, active-controlled clinical trial.
      SETTING: 623 sites in the United States and Canada. PATIENTS: Hypertensive
      patients 55 years of age or older with at least one additional risk factor for
      cardiovascular disease. INTERVENTION: Chlorthalidone (12.5 to 25 mg/d) or
      doxazosin (2 to 8 mg/d) for a planned follow-up of 4 to 8 years. MEASUREMENTS:
      Data on blood pressure, medication, and incident heart failure (treated outside
      hospital, hospitalized, or fatal) from February 1994 through December 1999.
      RESULTS: After the treatment groups were categorized as having no exposure to
      open-label medications (monotherapy) or exposure to open-label therapy, the
      relative risk for heart failure with doxazosin versus chlorthalidone was 3.10
      (CI, 2.51 to 3.82) and 1.42 (CI, 1.20 to 1.69), respectively. After adjustment
      for follow-up systolic/diastolic blood pressure, the overall relative risk was
      2.00 (CI, 1.72 to 2.32). CONCLUSION: In high-risk patients with hypertension, the
      higher risk for heart failure while taking doxazosin compared with chlorthalidone
      is attenuated but not eliminated by adding other antihypertensive drugs. The
      small observed difference in systolic blood pressure does not explain this
      increased risk.

PMID- 12204015
TI  - Angiotensin-converting enzyme gene polymorphism is associated with vulnerability
      to alcoholic cardiomyopathy.
AB  - BACKGROUND: Chronic alcohol abuse has a dose-dependent toxic effect on the
      myocardium, leading to alcoholic cardiomyopathy. The fact that only a minority of
      persons with chronic alcoholism have this condition suggests the possibility of a
      genetic vulnerability. In this context, polymorphism of the angiotensin
      converting enzyme (ACE) gene has been implicated in cardiac dysfunction.
      OBJECTIVE: To compare the ACE genotypes of alcoholic persons who have
      cardiomyopathy with those of comparable alcohol abusers who have normal cardiac
      function. DESIGN: Case-control study over a 2-year period. SETTING: An academic
      tertiary referral hospital in Barcelona, Spain. PATIENTS: 30 alcoholic men with
      symptomatic cardiomyopathy and 27 alcoholic men with normal cardiac function.
      MEASUREMENTS: Ethanol intake, cardiac status, left ventricular ejection fraction
      (LVEF), and ACE gene polymorphism. RESULTS: The DD ACE genotype was present in
      57% of alcoholic persons with an LVEF less than 0.50 and in 7% of those with
      normal cardiac function. Compared with persons who had an I allele, the odds
      ratio for development of left ventricular dysfunction in alcoholic persons with
      the DD genotype was 16.4. CONCLUSIONS: Vulnerability to cardiomyopathy among
      chronic alcohol abusers is partially genetic and is related to presence of the
      ACE DD genotype. This finding demonstrates genetic susceptibility to alcohol
      induced myocardial damage.

PMID- 12204016
TI  - Are bad outcomes from questionable clinical decisions preventable medical errors?
      A case of cascade iatrogenesis.
AB  - When a patient with multiple, complicated conditions is admitted to a hospital
      and risky procedures are performed that result in adverse outcomes, the
      difficulties inherent in determining whether and when a preventable medical error
      has occurred must be addressed. This article analyzes the case of a 40-year-old
      woman with a history of chronic aortic dissection and pericardial effusion who
      was admitted to a teaching hospital with unilateral swelling of her left breast
      and arm accompanied by dyspnea. During her hospitalization, the patient developed
      multiple complications from the diagnostic and therapeutic procedures that were
      performed. The authors argue that this case illustrates some limitations of
      routinely undertaking time-consuming and costly reviews, or "root-cause
      analyses," as a patient safety strategy when they are unlikely to reveal
      remediable "errors" or to suggest better systems of care that will prevent
      errors. The ability to establish causality through post hoc reviews is the
      linchpin in the recommendation for widespread adoption of error reporting and
      reviews. When causality is not established, it is impossible to know whether any
      changes adopted as a result of the reviews will be effective. This case, in which
      the causal pathways to the adverse events are very uncertain, may be much more
      typical than the egregious errors featured in a classic root-cause analysis. The
      authors recommend that the relative merits of this approach to patient safety be
      compared with other proven, cost-effective interventions to improve quality, such
      as appropriate treatment of myocardial infarction or depression, before scarce
      resources and enormous human capital are allocated for widespread implementation.

PMID- 12204017
TI  - Update in general internal medicine.

PMID- 12204018
TI  - Do ask, do tell.
AB  - As a consequence of bias and ignorance within the medical profession, lesbians
      and gay men frequently receive suboptimal health care. Knowledge of each
      patient's sexual orientation and behaviors is critical for the development of a
      productive therapeutic relationship, accurate risk assessment, and the provision
      of pertinent preventive counseling. However, clinicians often forget to ask about
      this information, and many lesbians and gay men are reticent to reveal the truth.
      I present vignettes from my personal experiences as a lesbian patient and doctor
      to illustrate the importance of creating an environment in which such disclosure
      can occur and to portray the challenges and rewards of coming out as a gay
      physician.

PMID- 12204019
TI  - Screening for breast cancer: recommendations and rationale.

PMID- 12204020
TI  - Breast cancer screening: a summary of the evidence for the U.S. Preventive
      Services Task Force.
AB  - PURPOSE: To synthesize new data on breast cancer screening for the U.S.
      Preventive Services Task Force. DATA SOURCES: MEDLINE; the Cochrane Controlled
      Trials Registry; and reference lists of reviews, editorials, and original
      studies. STUDY SELECTION: Eight randomized, controlled trials of mammography and
      2 trials evaluating breast self-examination were included. One hundred fifty-four
      publications of the results of these trials, as well as selected articles about
      the test characteristics and harms associated with screening, were examined. DATA
      EXTRACTION: Predefined criteria were used to assess the quality of each study.
      Meta-analyses using a Bayesian random-effects model were conducted to provide
      summary relative risk estimates and credible intervals (CrIs) for the
      effectiveness of screening with mammography in reducing death from breast cancer.
      DATA SYNTHESIS: For studies of fair quality or better, the summary relative risk
      was 0.84 (95% CrI, 0.77 to 0.91) and the number needed to screen to prevent one
      death from breast cancer after approximately 14 years of observation was 1224
      (CrI, 665 to 2564). Among women younger than 50 years of age, the summary
      relative risk associated with mammography was 0.85 (CrI, 0.73 to 0.99) and the
      number needed to screen to prevent one death from breast cancer after 14 years of
      observation was 1792 (CrI, 764 to 10 540). For clinical breast examination and
      breast self-examination, evidence from randomized trials is inconclusive.
      CONCLUSIONS: In the randomized, controlled trials, mammography reduced breast
      cancer mortality rates among women 40 to 74 years of age. Greater absolute risk
      reduction was seen among older women. Because these results incorporate several
      rounds of screening, the actual number of mammograms needed to prevent one death
      from breast cancer is higher. In addition, each screening has associated risks
      and costs.

PMID- 12204022
TI  - Screening mammography for younger women: back to basics.

PMID- 12204023
TI  - The mammography dilemma: a crisis for evidence-based medicine?

PMID- 12204025
TI  - A walk on the beach.

PMID- 12204026
TI  - Prognostic disclosure.

PMID- 12204028
TI  - Prognostic disclosure.

PMID- 12204029
TI  - Prognostic disclosure.

PMID- 12204030
TI  - Continuous positive airway pressure in patients without daytime sleepiness.

PMID- 12204032
TI  - Colloid use in the critically ill.

PMID- 12204034
TI  - Clinical assessment and D-dimer testing in deep venous thrombosis.

PMID- 12204036
TI  - Physicians and patient spirituality.

PMID- 12204038
TI  - Sprout-associated outbreaks.

PMID- 12204039
TI  - Newspaper reporting of screening mammography.

PMID- 12204041
TI  - Clozapine-associated neuroleptic malignant syndrome.

PMID- 12204042
TI  - Newspaper reporting of screening mammography.

PMID- 12204043
TI  - Superior sagittal sinus thrombosis and HIV.

PMID- 12204044
TI  - Metaphorical medicine: using metaphors to enhance communication with patients who
      have pulmonary disease.

PMID- 12204045
TI  - Summaries for patients. Mammograms in women age 40 to 49: results of the Canadian
      Breast Cancer Screening study.

PMID- 12204046
TI  - Summaries for patients. Blood pressure drugs and heart failure.

PMID- 12204047
TI  - Summaries for patients. Genetic variations and the risk for alcohol-induced
      weakness of the heart.

PMID- 12204048
TI  - Summaries for patients. Screening for breast cancer: recommendations from the
      U.S. Preventive Services Task Force.

PMID- 12204049
TI  - Rapidly progressive glomerulonephritis.

PMID- 12204050
TI  - The role of the autopsy in medical malpractice cases, I: a review of 99 appeals
      court decisions.
AB  - CONTEXT: Fear that damaging information from autopsy may be introduced as
      evidence in lawsuits alleging medical malpractice is often cited as one factor
      contributing to the decline in autopsy rates. OBJECTIVE: To determine how autopsy
      information influences the outcome of medical malpractice litigation. DESIGN: We
      studied state court records in 99 cases of medical malpractice adjudicated from
      1970 to the present to assess the role of information from autopsies in the
      outcomes. RESULTS: The 3 largest groups defined by cause of death at autopsy were
      acute pulmonary embolism, acute cardiovascular disease, and drug
      overdose/interaction. Findings for defendant physicians outnumbered medical
      negligence in the original trial proceedings by a 3:1 margin. The appellate
      courts affirmed 51 acquittals and 19 findings of negligence, and reversed the
      original trial court decision in 29 cases for technical reasons. We found no
      significant relationship between accuracy of clinical diagnosis (using the
      autopsy standard) and outcome of a suit charging medical negligence. Even when a
      major discrepancy existed between the autopsy diagnosis and the clinical
      diagnosis, and the unrecognized condition was deemed treatable, defendant
      physicians were usually exonerated. Moreover, major diagnostic discrepancies were
      relatively uncommon in suits in which a physician was found to be negligent.
      Conversely, in about 20% of cases, autopsy findings were helpful to defendant
      physicians. CONCLUSIONS: Our study confirms that a finding of medical negligence
      is based on standard-of-care issues rather than accuracy of clinical diagnosis.
      Autopsy findings may appear to be neutral or favorable to either the plaintiff or
      the defendant, but are typically not the crux of a successful legal argument for
      either side in a malpractice action. We conclude that fear of autopsy findings
      has no rational basis and is an important obstacle to uninhibited outcomes
      analysis.

PMID- 12204051
TI  - The role of the autopsy in medical malpractice cases, II: controversy related to
      autopsy performance and reporting.
AB  - CONTEXT: We studied 99 appellate court records in cases of alleged medical
      malpractice and found no relationship between discrepant clinical and autopsy
      findings and outcome of litigation. Standard-of-care issues and not diagnostic
      accuracy were at the heart of every case. OBJECTIVE: To characterize and discuss
      issues related to the autopsy and/or pathologist behavior that were raised in
      court records of medical malpractice litigation. DESIGN: In 18 appellate court
      records, issues were raised about quality of autopsy performance and reporting or
      about death certification. The details of these controversies are succinctly
      reported here in a manner intended to be instructive to pathologists who perform
      autopsies in a hospital setting or on a private fee-for-service basis.
      CONCLUSION: Autopsy reports are intended to provide objective medical information
      in a coherent format to the patient's medical record, to the attending physician
      and other concerned staff physicians, to other health care professionals, and to
      the families of the deceased. Inevitably, occasions arise that require legal
      counsel to be added to this list of parties with a legitimate interest. Our
      findings emphasize that incomplete, incoherent, obfuscated, or delayed reporting
      of autopsy findings do not meet professional standards, are unethical if
      intentional, and may be counterproductive.

PMID- 12204052
TI  - Q-tracks: a College of American Pathologists program of continuous laboratory
      monitoring and longitudinal tracking.
AB  - CONTEXT: Continuous monitoring of key laboratory indicators of quality by
      hundreds of laboratories in a standardized measurement program affords an
      opportunity to document the influence of longitudinal tracking on performance
      improvement by participants focused on that outcome. OBJECTIVE: To describe the
      results of the first 2 years of participation in a unique continuous performance
      assessment program for pathology and laboratory medicine. DESIGN: Participants in
      any of 6 modules in the 1999 and 2000 College of American Pathologists (CAP) Q
      Tracks program collected data according to defined methods and sampling intervals
      on standardized input forms. Data were submitted quarterly to CAP for statistical
      analysis. Interinstitutional comparison reports returned in 6 weeks provided each
      laboratory with its performance profile of key indicators and its percentile
      ranking compared with all participants in that quarter. This also included
      longitudinal comparisons of performance during previous cumulative quarters.
      Control charts graphically displayed data with flags identifying performance
      points that were out of statistical control. SETTING: Hospital-based laboratories
      in the United States (98%), Canada, and Australia. PARTICIPANTS: Voluntary
      subscriber laboratories in the CAP Q-Tracks performance measurement program:
      roughly 70% from hospitals of 300 occupied beds or fewer, 65% from private,
      nonprofit institutions, slightly more than half located in cities, one third from
      teaching hospitals, and 20% with pathology residency training programs. MAIN
      OUTCOME MEASURES: Each module measured several major and additional minor quality
      indicators and unbenchmarked individualized data for internal use. RESULTS:
      Participants in 4 of 6 Q-Tracks continuous monitors demonstrated statistically
      significant performance improvement trends in 1999 and 2000, which were most
      marked for laboratories that continued participation throughout both years. These
      monitors were wristband patient identification, laboratory specimen
      acceptability, blood product wastage, and intraoperative frozen section
      consultation. CONCLUSIONS: Key continuous indicators chosen on the basis of a
      decade's experience in the CAP Q-Probes quality improvement program are useful
      measurement and benchmarking tools for laboratories to improve performance. In
      general, measures in which there is a broad range of demonstrable performance
      initially are most optimal for subsequent improvement using continuous
      monitoring. These studies have shown that quality is not static, but rather is a
      moving benchmark of performance as seen in the redefinition of benchmarks over
      time by participants in the first 2 years of the CAP Q-Tracks program.

PMID- 12204053
TI  - Intraoperative parathyroid hormone testing: survey of testing program
      characteristics.
AB  - OBJECTIVE: To examine the number and testing characteristics of laboratories that
      offer intraoperative testing of intact parathyroid hormone (PTH). DESIGN:
      Laboratories (n = 355) that participated in 2001 in PTH proficiency testing with
      the College of American Pathologists Special Ligand Survey were surveyed about
      intraoperative PTH testing. RESULTS: Of the 320 laboratories that responded to
      the survey, 92 performed intraoperative PTH testing. Testing practices were
      divided nearly equally among laboratories that performed intraoperative PTH
      testing for all parathyroidectomies (40%), most but not all cases (31%), and less
      than half of cases (30%). Testing frequency usually was low, with about two
      thirds of laboratories reporting 5 or fewer cases per month. A surprising finding
      was that, although intraoperative PTH testing originally became widely practiced
      as a point-of-care test, 71% of laboratories performed testing in a central
      laboratory, 6% in satellite laboratories, and only 23% in operating suites. A
      survey of methods showed that 33% used the manual QuiCk-Intraoperative test, 47%
      used the automated Immulite Turbo intact PTH assay, and 20% used other methods.
      CONCLUSIONS: Intraoperative testing of intact PTH, although relatively new, has
      come into widespread practice during parathyroid surgery. Service delivery has
      evolved from a point-of-care model toward a central laboratory model, with this
      test serving as an illustrative example of factors that affect the balance
      between point-of-care and laboratory testing.

PMID- 12204054
TI  - Colonic adenocarcinoma metastatic to the urinary tract versus primary tumors of
      the urinary tract with glandular differentiation: a report of 7 cases and
      investigation using a limited immunohistochemical panel.
AB  - OBJECTIVE: To determine whether a limited immunohistochemical panel can help
      differentiate metastatic colonic adenocarcinoma from primary enteric-type
      adenocarcinoma of the urinary tract and urothelial (transitional cell) carcinoma
      with glandular differentiation, which appear morphologically similar but most
      often necessitate different treatment protocols. DESIGN: We examined lower
      urinary tract tumors (5 urinary bladder, 2 urethral) from 7 patients with a
      history of colonic adenocarcinoma. The differential diagnoses in these cases
      included metastatic colonic adenocarcinoma, primary enteric-type adenocarcinoma
      of the urinary tract, and urothelial carcinoma with glandular differentiation. An
      immunohistochemical panel consisting of cytokeratin 7 (CK-7), cytokeratin 20 (CK
      20), and villin was evaluated in all cases. Four primary enteric-type
      adenocarcinomas of the urinary tract and 5 conventional urothelial carcinomas
      were also studied to compare morphologic features and immunohistochemical
      staining patterns. RESULTS: Of the 7 cases, 6 were determined to be metastatic
      colonic adenocarcinoma and 1 was diagnosed as a primary urothelial carcinoma with
      glandular differentiation. All 6 metastatic colonic adenocarcinomas, 6 of the 7
      primary colonic adenocarcinomas, and all 4 primary enteric-type adenocarcinomas
      of the urinary tract were CK-20 positive (1 was CK-20 negative), villin positive,
      and CK-7 negative. The single urothelial carcinoma with glandular differentiation
      and all 5 control cases of urothelial carcinoma were CK-7 and CK-20 positive, and
      villin negative. CONCLUSIONS: We conclude that (1) villin is expressed in primary
      enteric-type adenocarcinoma of the urinary tract; (2) in difficult cases,
      urothelial carcinoma with glandular differentiation can be distinguished from
      colonic adenocarcinoma because the former is CK-7 positive, CK-20 positive, and
      villin negative, whereas the latter is CK-20 positive, villin positive, and CK-7
      negative; (3) clinical information is essential when evaluating lower urinary
      tract tumors that are clinically and morphologically similar to enteric-type
      adenocarcinoma of the urinary tract; and (4) the similar immunohistochemical
      profiles of metastatic colonic adenocarcinoma and primary enteric-type
      adenocarcinoma of the urinary tract may be in keeping with the hypothesis that
      the latter arise from intestinal metaplasia.

PMID- 12204055
TI  - Acute fibrinous and organizing pneumonia: a histological pattern of lung injury
      and possible variant of diffuse alveolar damage.
AB  - CONTEXT: The histologic patterns of diffuse alveolar damage (DAD), bronchiolitis
      obliterans with organizing pneumonia (BOOP), and eosinophilic pneumonia (EP) are
      well-recognized histologic patterns of lung injury associated with an acute or
      subacute clinical presentation. We have recognized acute fibrinous and organizing
      pneumonia (AFOP) as a histologic pattern, which also occurs in this clinical
      setting but does not meet the classic histologic criteria for DAD, BOOP, or EP
      and may represent an underreported variant. OBJECTIVE: To investigate the
      clinical significance of the AFOP histologic pattern and to explore its possible
      relationship to other disorders, including DAD and BOOP. DESIGN: Open lung biopsy
      specimens and autopsy specimens were selected from the consultation files of the
      Armed Forces Institute of Pathology, which showed a dominant histologic pattern
      of intra-alveolar fibrin and organizing pneumonia. Varying amounts of organizing
      pneumonia, type 2 pneumocyte hyperplasia, edema, acute and chronic inflammation,
      and interstitial widening were seen. Cases with histologic patterns of classic
      DAD, BOOP, abscess formation, or eosinophilic pneumonia were excluded. To
      determine the clinical behavior of patients with this histologic finding,
      clinical and radiographic information and follow-up information were obtained.
      Statistical analysis was performed using Kaplan-Meier and chi(2) analysis.
      RESULTS: Seventeen patients (10 men, 7 women) with a mean age of 62 years (range,
      33-78 years) had acute-onset symptoms of dyspnea (11), fever (6), cough (3), and
      hemoptysis (2). Associations believed to be clinically related to the lung
      disease included definitive or probable collagen vascular disease (3), amiodarone
      (1), sputum culture positive for Haemophilus influenza (1), lung culture positive
      for Acinetobacter sp. (1), lymphoma (1), hairspray (1), construction work (1),
      coal mining (1), and zoological work (1). Six patients had no identifiable origin
      or association. Follow-up revealed 2 clinical patterns of disease progression: a
      fulminate illness with rapid progression to death (n = 9; mean survival, 0.1
      year) and a more subacute illness, with recovery (n = 8). Histologic analysis and
      initial symptoms did not correlate with eventual outcome, but 5 of the 5 patients
      who required mechanical ventilation died (P =.007). CONCLUSIONS: Acute fibrinous
      and organizing pneumonia is a histologic pattern associated with a clinical
      picture of acute lung injury that differs from the classic histologic patterns of
      DAD, BOOP, or EP. Similar to these patterns of acute lung injury, the AFOP
      pattern can occur in an idiopathic setting or with a spectrum of clinical
      associations. The overall mortality rate is similar to DAD and therefore may
      represent a histologic variant; however, AFOP appears to have 2 distinct patterns
      of disease progression and outcome. The need for mechanical ventilation was the
      only parameter that correlated with prognosis. None of the patients with a
      subacute clinical course required mechanical ventilation.

PMID- 12204056
TI  - Beta-catenin accumulation and gene mutation in exon 3 in dedifferentiated
      liposarcoma and malignant fibrous histiocytoma.
AB  - CONTEXT: beta-Catenin is an adhesion molecule that also plays a role in the Wnt
      signaling pathway. Objective.-To analyze beta-catenin mutation and accumulation
      in a series of liposarcomas and malignant fibrous histiocytomas. DESIGN: beta
      Catenin mutation in exon 3 was studied using polymerase chain reaction-single
      strand conformation polymorphism (PCR-SSCP) and direct sequencing analysis in 30
      formalin-fixed, paraffin-embedded liposarcomas. The tumors included 12
      dedifferentiated liposarcomas, characterized by both high-grade anaplastic
      components and well-differentiated liposarcoma components, plus 18 well
      differentiated liposarcomas (10 lipoma-like and 8 sclerosing-type cases). The 2
      components of dedifferentiated liposarcomas were analyzed independently. beta
      Catenin accumulation in the nuclei or cytoplasm and Ki-67 expression (cell
      proliferation marker, MIB-1 labeling index) were examined immunohistochemically.
      Nine storiform-pleomorphic-type malignant fibrous histiocytomas were also
      studied. RESULTS: Dedifferentiated liposarcomas showed mutation in 2 cases (17%)
      and accumulation in 5 cases (42%). One of the 2 cases that showed mutations had a
      mutation in the well-differentiated component; this mutation was silent. The
      other case had mutations that differed between the 2 components. In well
      differentiated liposarcomas, mutation was not seen in any of the cases (0/18;
      0%); however, accumulation was seen frequently in the sclerosing-type cases (5/8;
      63%), but not in the lipoma-like cases (0/10; 0%). Malignant fibrous
      histiocytomas showed mutation and accumulation in 5 (56%) and 4 (44%) cases,
      respectively, without any exact correlation between the cases. Cases with
      accumulation had a higher MIB-1 labeling index than those without, among both the
      sclerosing-type well-differentiated liposarcomas (P <.05) and the malignant
      fibrous histiocytomas. CONCLUSIONS: Our results suggest the possible involvement
      of beta-catenin activation caused by beta-catenin mutation in liposarcoma and
      malignant fibrous histiocytoma, but the contribution would seem to be different,
      depending on the tumor type. beta-Catenin accumulation is also thought to be
      related to cell proliferation in some of the cases.

PMID- 12204057
TI  - DNA topoisomerase II-alpha and cyclin A immunoexpression in meningiomas and its
      prognostic significance: an analysis of 263 cases.
AB  - CONTEXT: Routine pathologic examination cannot distinctively predict the clinical
      course of meningiomas because even histologically benign tumors may recur after
      gross total resection. Therefore, numerous efforts have been made to evaluate the
      meningioma growth fraction and its prognostic value. However, a universally
      applicable proliferative marker for meningioma outcome is not yet a reality.
      OBJECTIVE: To investigate the prognostic utility of 3 proliferative markers,
      namely, Ki-67, DNA topoisomerase II-alpha (topoII), and cyclin A in a
      representative series of intracranial meningiomas. DESIGN: Two hundred sixty
      three adult patients with intracranial meningiomas (208 benign, 42 atypical, and
      13 anaplastic) were studied retrospectively. Tumor specimens were
      immunohistochemically examined with antibodies to Ki-67 (MM-1), topoII, and
      cyclin A. A computerized color image analyzer was used to count immunostained
      nuclei. RESULTS: The topoII and cyclin A scores exhibited a close correlation
      with Ki-67 immunostaining. Significant differences between the indices for all 3
      markers were noted among the 3 grades of meningiomas. The scores for all 3
      markers were significantly different between recurrent and nonrecurrent
      meningiomas, including benign tumors that were treated with gross total
      resection. Recurrence-free survival was significantly reduced for cases with a Ki
      67 labeling index (LI) of 4.4% or greater, a topoII LI of 3.2% or greater, and a
      cyclin A LI of 3.1% or greater. Multivariate analysis revealed that the risk of
      recurrence for the entire meningioma cohort was significantly associated with
      tumor grade (hazard ratio = 2.7; P =.004), topoII LI of 3.2% or greater (hazard
      ratio = 5.5; P <.001), and a cyclin A LI of 3.1% or greater (hazard ratio = 2.4;
      P =.01). CONCLUSIONS: There is a close correlation in the expression of these 3
      proliferative markers in meningiomas, and all of the markers showed a significant
      association with tumor grade, recurrence rate, and recurrence-free survival.
      Consequently, in addition to Ki-67, immunoexpression of topoII and cyclin A is
      available for predicting meningioma recurrence. Moreover, the topoII and cyclin A
      staining scores were found to be more sensitive predictors for meningioma
      progression than Ki-67 and, therefore, either of these 2 markers may prove to be
      clinically informative and useful.

PMID- 12204058
TI  - Prevalence of the 20210 G-->A prothrombin variant and its association with
      coronary artery disease in a Middle Eastern Arab population.
AB  - BACKGROUND: No reports are available on the distribution of the 20210 G-->A
      prothrombin variant among Middle Eastern Arabs. Additionally, to date, studies
      that attempt to establish this polymorphism as an independent risk factor or as a
      predictor for coronary artery disease (CAD) have yielded conflicting results.
      OBJECTIVE: To determine the prevalence of the 20210 G-->A prothrombin variant
      among Middle Eastern Arabs and to evaluate the potential relevance of this
      variant to Arab patients with angiographically documented CAD. METHODS AND
      RESULTS: We used the polymerase chain reaction and restriction enzyme digestion
      to determine the prevalence of this polymorphism in 613 individuals from Arabic
      ethnic origin with CAD and from 593 healthy blood donors (BDs) from an identical
      ethnic background. Within the BD group (n = 593), 10 individuals (1.7%) were
      heterozygous, 583 individuals (98.3%) were normal, and none were homozygous for
      the 20210 G-->A prothrombin variant. Within the CAD group (n = 613), 13
      individuals (2.1%) were heterozygous, 600 individuals (97.9%) were normal, and
      none were homozygous for the 20210 G-->A prothrombin variant. A chi(2) analysis
      was used to evaluate any significance in the distribution of genotypes. A value
      of 1.23 was obtained. Values less than 3.84 indicate no statistically significant
      difference between the heterozygous carriers of the 20210A allele in both study
      groups. CONCLUSIONS: In our population of Middle Eastern Arabs, the presence of
      the 20210 G-->A prothrombin variant is not associated with patients with
      angiographically documented CAD. Therefore, this variant cannot be considered as
      an independent risk factor or as a predictor for CAD in this population.

PMID- 12204059
TI  - Autopsy findings following gastric bypass surgery for morbid obesity.
AB  - BACKGROUND: Roux-en-Y gastric bypass, currently the most frequently performed
      surgical procedure for morbid obesity, has a low but significant mortality rate.
      There are limited data documenting the findings at necropsy in patients who have
      died following this procedure. OBJECTIVE: To determine cause of death and
      pathologic processes present in obese subjects dying after gastric bypass
      surgery. PATIENTS: We studied 10 patients who underwent autopsy following gastric
      bypass surgery for morbid obesity between the years 1994 and 2000. RESULTS: There
      were 6 men and 4 women. The mean age of the patients was 48 years (range, 28-62
      years). The mean preoperative weight was 162 kg (range, 112-245 kg), and the mean
      body mass index was 54 kg/m(2) (range, 39-76 kg/m(2)), similar to all patients
      undergoing gastric bypass at our institution during the same period. Five deaths
      were directly attributable to technical complications. Five deaths were
      attributed to underlying comorbid conditions. One patient died of cirrhosis and
      one of pulmonary hemorrhage. Three patients died from pulmonary embolism.
      However, 8 of 10 patients had microscopic evidence of pulmonary emboli, despite
      prophylaxis for deep vein thrombosis. Most patients had some degree of
      steatohepatitis and hepatic fibrosis (80% and 70%, respectively). There were no
      deaths from primary cardiac events. CONCLUSIONS: In patients who die after Roux
      en-Y gastric bypass, half die due to technical complications, whereas the other
      half die of complications of their obesity. Clinically, only 20% of patients were
      suspected to have pulmonary emboli, yet at autopsy, 80% of patients had pulmonary
      emboli. In morbidly obese patients undergoing Roux-en-Y gastric bypass, there is
      an unexpectedly high rate of clinically silent pulmonary emboli contributing to
      morbidity and mortality.

PMID- 12204060
TI  - ras Gene mutations and expression of Ras signal transduction mediators in gastric
      adenocarcinomas.
AB  - OBJECTIVE: To investigate ras gene alteration in human gastric adenocarcinomas
      and its potential relationship to ras signal transduction mediators. DESIGN:
      Genomic DNA from 104 gastric tumors were analyzed by sequencing of polymerase
      chain reaction-amplified products for the presence of ras mutations. All the
      samples were further investigated with the use of immunohistochemical analysis
      for ERK1 and ERK2. SETTING: Tertiary care teaching hospital. PATIENTS: Seventy
      patients from a Korean population and 34 from a Midwestern US population composed
      of white Americans and African Americans. RESULTS: Fifteen tumors (14%) were
      positive for either H-ras or K-ras mutation: 9 (13%) of 70 Korean patients and 6
      (18%) of 34 US patients. Seven (78%) of the 9 mutated tumors from Korean patients
      and all 6 (100%) from the US patients were intestinal-type lesions. Either ERK1
      and/or ERK2 was overexpressed in 68 samples (65%). No association was established
      between ras mutations and overexpression of ERK1/2. However, the correlation
      between ERK1/2 and progression (early vs late) was statistically significant (P
      =.007). CONCLUSIONS: These data suggest that ras mutations are uncommon in
      gastric adenocarcinomas and that differing racial and/or geographic mechanisms
      may not underlie ras gene alteration. Most ras mutations were, however, observed
      in the group of intestinal-type samples, supporting the different genetic
      mechanisms of carcinogenesis between the intestinal- and diffuse-type tumors. It
      is noteworthy that enhanced ERK1/2 activity could be one of the characteristics
      of tumor invasiveness in gastric cancers.

PMID- 12204061
TI  - Immunohistochemical confirmation of pulmonary papillary adenocarcinoma metastatic
      to ovaries.
AB  - Metastatic papillary adenocarcinomas of the ovary are rare compared to primary
      ovarian papillary serous carcinomas. We report a case of pulmonary papillary
      adenocarcinoma metastatic to the ovary and show how this tumor can be
      differentiated immunohistochemically from an ovarian primary. Paraffin blocks of
      the ovarian tumor were analyzed for carcinoembryonic antigen, CA 125, surfactant,
      E-cadherin, N-cadherin, and vimentin. These markers are useful in differentiating
      epithelial tumors of lung versus ovarian origin. The papillary tumor showed
      expression of carcinoembryonic antigen, surfactant, and E-cadherin, but was
      negative for CA 125, N-cadherin, and vimentin. These findings support a lung
      carcinoma metastatic to the ovary.

PMID- 12204062
TI  - Dedifferentiated acinic cell carcinoma of the parotid gland with myoepithelial
      features.
AB  - Dedifferentiated acinic cell carcinoma of the salivary gland is an uncommon
      variant of acinic cell carcinoma, characterized by the coexistence of both an
      usual low-grade acinic cell carcinoma and a high-grade dedifferentiated
      component, as well as by an accelerated clinical course. We describe a case of
      acinic cell carcinoma of the parotid gland in a 67-year-old woman, which recurred
      4 times after surgery and radiotherapy. The recurrences consisted of residual
      foci of acinic cell carcinoma intermingled with a high-grade epithelial
      proliferation; the latter was focally constituted by cells with morphologic and
      immunohistochemical features of myoepithelium.

PMID- 12204063
TI  - Primary yolk sac tumor of the urachus.
AB  - Pure yolk sac tumor is the most common malignant gonadal tumor of infants and
      toddlers. However, the majority of extragonadal germ cell tumors in the midline
      are either seminomas (germinomas) or teratomas, and pure yolk sac tumors account
      for only a small fraction of these lesions. To date, only 1 primary urachal pure
      yolk sac tumor has been reported in the literature. We describe another case,
      occurring in a 7-month-old male infant who presented with a rapidly enlarging
      intra-abdominal tumor with marked engorgement of the superficial venous plexus
      around the umbilicus. With periodic follow-up for 3 years following surgical
      extirpation of the tumor and adjuvant chemotherapy, this patient is still alive
      without evidence of disease. Notably, the glandular elements predominating in the
      frozen sections resulted in the initial misdiagnosis of the tumor as a urachal
      adenocarcinoma, although the entirely resected specimen revealed typical
      histologic patterns and Schiller-Duval bodies. Immunohistochemistry showed that
      the tumor cells were diffusely reactive to alpha-fetoprotein, alpha(1)
      antitrypsin, and cytokeratin. Tumor cells were negative for p53 protein, but
      revealed overexpression for MDM2 protein. Flow cytometry demonstrated a diploid
      DNA content with S-phase being as high as 55.36%. This case emphasizes that pure
      yolk sac tumor can occur primarily in the remnant of the urachus in young
      children.

PMID- 12204064
TI  - Malignant melanoma of the oral mucosa in a 17-year-old adolescent girl.
AB  - Mucosal melanomas of the oral cavity are rarely seen in the United States. The
      hard palate is the most common intraoral site. This unusual case occurred in the
      oral cavity of a 17-year-old Asian girl, who presented to her dentist with
      complaints of pain and swelling in the upper jaw. The lesion was distal and
      palatal to the maxillary left second molar, which was vital. Interestingly, the
      clinical presentation was a hyperplastic, tender lesion that bled when probed.
      Histopathologically, the biopsy demonstrated a sheet of spindle-shaped cells
      arranged in nests and fascicles. The nuclei were vesicular, oval to spindle
      shaped, and some contained nucleoli that were distinguishable but not prominent.
      No melanin pigment was observed in the lesion. Tumor cells strongly expressed
      S100 protein, gp100 (HMB-45), and microphthalmia transcription factor, and
      variably expressed MART1, but not cytokeratins, CD34, or muscle-specific actin.
      The histopathologic features and immunohistochemical findings are consistent with
      a diagnosis of malignant melanoma.

PMID- 12204065
TI  - Carcinosarcoma of the pancreas: a case report and review of the literature.
AB  - We report the case of a 74-year-old white man with a mass in the head of the
      pancreas, which was found incidentally on computerized tomographic scan during a
      workup for deep vein thrombosis. Endoscopy with pancreatic duct brushings yielded
      a diagnosis of adenocarcinoma. A pancreaticoduodenectomy followed, with complete
      resection of the tumor. Pathologic examination showed 2 distinct components. One
      component was a conventional infiltrating pancreatic ductal adenocarcinoma, and
      the other component was high-grade sarcoma with features of malignant fibrous
      histiocytoma. To our knowledge, this carcinosarcoma is the seventh reported case
      of a primary pancreatic neoplasm with mixed carcinomatous and sarcomatous
      elements.

PMID- 12204066
TI  - Incidentally detected giant oncocytoma arising in retroperitoneal heterotopic
      adrenal tissue.
AB  - A nonfunctional retroperitoneal oncocytoma incidentally discovered in a 40-year
      old woman is described. The tumor, which was 17 cm in largest dimension, was
      completely separated from the kidneys and adrenal glands and consisted of nests
      of polygonal cells with large, granular, eosinophilic cytoplasm. Significant
      nuclear atypia, necrosis, and mitosis were absent. Ultrastructural analysis
      confirmed the oncocytic nature of the neoplastic cells. Since neoplastic cells
      were not immunoreactive for chromogranin and did not contain dense-core secretory
      granules, the diagnosis of oncocytic paraganglioma was excluded. Cells
      immunoreactive for 3beta-hydroxysteroid dehydrogenase, the enzyme catalyzing the
      conversions of pregnenolone to progesterone and dehydroepiandrosterone to
      androstenedione, were identified in the tumor, thus strongly indicating
      adrenocortical tissue origin. Multiple nests of 3beta-hydroxysteroid
      dehydrogenase-positive cells were detected in the loose retroperitoneal
      connective tissue. These findings strongly support the origin of the tumor from
      heterotopic retroperitoneal rests of the adrenal gland. To our knowledge, only 1
      similar case has been described in the literature to date.

PMID- 12204067
TI  - A piece of my mind: secondary consult.

PMID- 12204068
TI  - Continuing medical education and the physician as a learner: guide to the
      evidence.

PMID- 12204069
TI  - Variability in deans' letters.

PMID- 12204070
TI  - Use of medical journals among pediatric educators.

PMID- 12204071
TI  - Teaching cardiovascular anatomy to medical students by using a handheld
      ultrasound device.

PMID- 12204072
TI  - Family medicine training in rural areas.

PMID- 12204073
TI  - Educational programs in US medical schools, 2001-2002.
AB  - We used data mainly from the 2001-2002 Liaison Committee on Medical Education
      Annual Medical School Questionnaire, which had a 100% response rate, to describe
      the status of US medical education programs. In 2001-2002, the number of full
      time medical school faculty members was 104 949, a 2.4% increase from 1999-2000.
      The 34,859 applicants for the class entering in 2001 represented a 9.5% decrease
      from the number of applicants in 1999-2000. There were 2 applicants for every
      acceptance, and the academic qualifications of medical students entering in 2001
      were unchanged from 1999. Women comprised 47.8% of entering students in 2001, and
      13.1% were members of underrepresented minority groups. Of all first-year
      students, 67% were in-state residents. Most medical schools had mandatory
      required night call during at least some required clinical clerkships, but only
      17 had formal policies on medical student work hours. In 74 schools (60%),
      medical students were required to pass Steps 1 and 2 of the United States Medical
      Licensing Examination to advance or graduate.

PMID- 12204074
TI  - US graduate medical education, 2001-2002: changing dynamics.
AB  - The National Graduate Medical Education (GME) Census, jointly administered by the
      American Medical Association and the Association of American Medical Colleges,
      completed its second year as an online survey of all GME programs accredited by
      the Accreditation Council for Graduate Medical Education as well as combined
      specialty programs approved by their corresponding medical specialty boards.
      Continuing trends include the growing number of subspecialty programs, which
      increased by 65 since last year to 3822, and a smaller number of specialty
      programs, which decreased by 25 to 4203. There were corresponding shifts in the
      number of residents training in them. The number of graduates from osteopathic
      medical schools in allopathic GME has increased from 3288 in 1996-1997 to 4658 in
      2001-2002, an increase of 42%. Overall, the total number of residents in GME has
      declined slightly, to an estimated 96 410 this year. The number of residents in
      graduate year 1 (GY1) positions (entry positions in GME, for which prior training
      is not required) has also decreased, although the proportion of residents in GY1
      positions who have not had prior GME has increased. The number of international
      medical graduates (IMGs) in GY1 positions has decreased from a high of 6727 in
      1999-2000 to 5898 in 2001-2002, a decrease of 12.3%. However, the number who have
      entered GME immediately on graduation has grown from 310 in 1996-1997 to 936 in
      2001-2002. Most of these IMGs were citizens or permanent residents of the United
      States and attended medical schools in the Caribbean. New race and ethnicity
      questions, which parallel those of the US Census, continue to reveal disparities
      in the racial/ethnic distribution of the training physician population relative
      to the US population. Despite continued interest in resident work hours, there
      was no decrease in reported hours worked between 2000-2001 and 2001-2002.
      Physicians training in surgical specialties are reported to work the most hours
      per week, while internal medicine and pediatrics allow for the most consecutive
      time on duty, at 30 hours or more. Specialties and subspecialties with limited on
      call schedules, such as forensic psychiatry and pediatric pathology, have, on
      average, the lowest number of duty hours.

PMID- 12204075
TI  - The changing pool of international medical graduates seeking certification
      training in US graduate medical education programs.
AB  - International medical graduates (IMGs) consistently represent approximately one
      fourth of both the physician workforce and the graduate medical education (GME)
      population of the United States. To enter into accredited US GME programs, IMGs
      must be certified by the Educational Commission for Foreign Medical Graduates
      (ECFMG). Changes in the number and characteristics of those seeking certification
      directly affect the GME population and the future physician workforce in the
      United States. In July 1998, in response to concerns that IMGs might be lacking
      in basic clinical skills (eg, history taking, physical examinations,
      communicating with patients in spoken English), the ECFMG initiated a requirement
      that IMGs pass a clinical skills assessment (CSA) to achieve ECFMG certification.
      In this study we examined the pool of IMGs seeking certification, using databases
      reporting on all individuals beginning the certification process from 1995
      through 2001. For this period, we found that the number of IMG candidates taking
      the Step 1 examination decreased by 45.5% (36,983 vs 16,828), and the number of
      IMGs registered to take Step 2 decreased by 38.1% (31 751 vs 12 122). The number
      of ECFMG certificates issued annually decreased, from a range of 9000 to 12,000
      (1995-1998) to fewer than 6000 (1999-2001). Although the number of IMGs annually
      seeking and receiving certification has decreased, the quality of the applicants
      appears to have improved and the number of IMGs certified annually continues to
      adequately fill GME positions not taken by US medical graduates.

PMID- 12204076
TI  - Assessing readiness for medical education: evolution of the medical college
      admission test.
AB  - The attrition rate of 5% to 50% from US medical schools in the 1920s propelled
      the development of a test that would measure aptitude for medical studies. Since
      its development in 1928, the Medical College Admission Test (MCAT) has undergone
      5 revisions. The first version was divided into 6 to 8 subtests that focused on
      memory, knowledge of scientific terminology, reading and comprehension, and
      logic. The second, which appeared in 1946, was reduced to 4 categories: verbal
      and quantitative skills, science knowledge, and added a category called
      understanding modern society. The major difference in the third version, launched
      in 1962, expanded the test's understanding modern society section to a broader
      test of general information. In 1977, the MCAT underwent its fourth change: its
      science section, reading and quantitative skill assessment sections were
      expanded; its general liberal arts knowledge section was eliminated; its scoring
      report structure and scoring range were altered; and its cultural and social bias
      was minimized. The current version, beginning in 1991, has undergone another
      significant change. Although it does not contain independent measures of either
      liberal arts or numeracy as separate categories, quantitative skills are needed
      to solve some of the problems in biological and physical sciences. However, its
      principal innovation is the writing sample section. Through its 74-year history,
      the various renditions of the MCAT demonstrate that the definition of aptitude
      for medical education reflects the professional and social mores and values of
      the time.

PMID- 12204077
TI  - Reentry into clinical practice: challenges and strategies.
AB  - Women and men who reenter clinical practice after a period of clinical inactivity
      often face personal, professional, and institutional obstacles. Although many
      associations and academic medical institutions realize the critical importance of
      retaining and promoting highly qualified individuals, it is equally important for
      health care professionals to have the opportunity to return to a successful
      professional career following extended clinical inactivity. Here we provide a
      review of factors that may contribute to clinical inactivity, discuss challenges
      associated with the reentry process, describe current reentry efforts, and
      propose recommendations for future directions.

PMID- 12204078
TI  - Family practice in the United States: a status report.
AB  - Since family practice was first recognized as a specialty in the late 1960s,
      considerable intellectual and organizational change has occurred in medicine,
      especially during the 1990s. To reflect on and reconsider the role of family
      practice in US health care, this article reviews the development of family
      practice as a specialty, provides a current assessment of the status of family
      medicine in the United States, and comments on issues that are of ongoing
      importance to family practice.

PMID- 12204079
TI  - Tobacco intervention training: current efforts and gaps in US medical schools.
AB  - CONTEXT: Research has documented that US medical schools inadequately teach
      tobacco intervention skills. OBJECTIVE: To examine effective training methods for
      tobacco intervention in undergraduate medical education. DATA SOURCES: Using
      indexing terms related to tobacco intervention and medical education, we searched
      MEDLINE (1966-June 2002) and the Cochrane Database of Systematic Reviews (through
      issue 2, 2002). Reference lists of relevant articles were also read to identify
      additional articles. Because of their importance to tobacco intervention, we also
      reviewed Ockene and colleagues' tobacco education research and the tobacco
      treatment guidelines of the United States Public Health Service and the United
      States Preventive Services Task Force. STUDY SELECTION: All study designs that
      incorporated process or outcome evaluation of tobacco intervention educational
      methods for medical students were included in this review. Of an initial 1241
      articles retrieved, 82 included medical students. Reviewing abstracts and
      references of these articles identified 13 pertinent studies. DATA EXTRACTION:
      Quality criteria for inclusion consisted of explicit evaluation of the
      educational methods used. Data extraction identified all evaluations and any
      problems in program implementation. DATA SYNTHESIS: Enhanced instructional
      methods (eg, the use of patient-centered counseling, standardized patient
      instructors, role playing, or a combination of these) are more effective for
      teaching tobacco intervention than are traditional didactic methods alone and can
      be effectively inserted into medical school curricula. CONCLUSIONS: Various
      educational methods have been used to train medical students in tobacco
      intervention. Nonetheless, gaps still exist within undergraduate medical
      education, including a lack of integration of tobacco dependence information
      throughout all 4 years of medical school curricula, specific training in
      smokeless tobacco intervention, tobacco intervention training that addresses
      cultural issues, and long-term studies showing that such training is retained.

PMID- 12204080
TI  - Evaluating the teaching of evidence-based medicine.

PMID- 12204081
TI  - New requirements for resident duty hours.

PMID- 12204084
TI  - Female genital mutilation.

PMID- 12204082
TI  - Sleep loss and fatigue in residency training: a reappraisal.
AB  - Reduced sleep time is commonplace for many interns and residents. Recent studies,
      however, suggest that sleep loss and fatigue result in significant
      neurobehavioral impairments in healthy young adults. We reviewed studies
      addressing the effects of sleep loss on cognition, performance, and health in
      surgical and nonsurgical residents. We describe the effectiveness of
      countermeasures for sleepiness, including recent work-hour restrictions. A more
      complete understanding of the issues of sleep loss during residency training can
      inform innovative strategies to minimize the effects of sleepiness and fatigue on
      patient care and resident safety.

PMID- 12204085
TI  - When cultures are wrong.

PMID- 12204086
TI  - Covenant and the vulnerable other.

PMID- 12204087
TI  - A woman's rite to health.

PMID- 12204088
TI  - Beatrice's choice.

PMID- 12204089
TI  - Medical schools in the United States.

PMID- 12204090
TI  - Medical schools in Canada.

PMID- 12204091
TI  - Graduate medical education.

PMID- 12204092
TI  - Enzyme activity after resealing within ghost erythrocyte cells, and protection by
      alpha-crystallin against fructose-induced inactivation.
AB  - The role of alpha-crystallin as a molecular chaperone has been shown in many in
      vitro studies. In the present paper, we report on the chaperone function of alpha
      crystallin within resealed erythrocyte ghosts. Eight enzymes were individually
      resealed within erythrocyte ghosts and assayed at zero time and at 24 h. The
      ghost cell suspension was separated into soluble and membrane fractions. Five of
      the enzymes had significantly greater enzyme activity after 24 h than the control
      within the soluble fractions. Fructation caused a decrease in enzyme activity
      (relative to the control). Resealing of alpha-crystallin within the ghost cell
      alongside the enzymes protected against inactivation by fructose within the
      soluble fraction.

PMID- 12204093
TI  - Anti-viral activity of red microalgal polysaccharides against retroviruses.
AB  - Red microalgal polysaccharides significantly inhibited the production of
      retroviruses (murine leukemia virus- MuLV) and cell transformation by murine
      sarcoma virus(MuSV-124) in cell culture. The most effective inhibitory effect of
      these polysaccharides against both cell transformation and virus production was
      obtained when the polysaccharide was added 2 h before or at the time of
      infection. Although, addition of the polysaccharide post-infection significantly
      reduced the number of transformed cells, but its effect was less marked than that
      obtained when the polysaccharide was added before or at the time of infection.The
      finding that the inhibition of cell transformation by MuSV-124 was reversible
      after removal of the polysaccharide suggested that microalgal polysaccharides
      inhibited a late step after provirus integration into the host genome. In
      conclusion, our findings could support the possibility that the polysaccharide
      may affect early steps in the virus replication cycle, such as virus absorption
      into the host cells, in addition to its effect on a late step after provirus
      integration.

PMID- 12204094
TI  - Pro-domain removal in ASP-2 and the cleavage of the amyloid precursor are
      influenced by pH.
AB  - BACKGROUND: One of the signatures of Alzheimer's disease is the accumulation of
      aggregated amyloid protein, Abeta, in the brain. Abeta arises from cleavage of
      the Amyloid Precursor protein by beta and gamma secretases, which present
      attractive candidates for therapeutic targeting. Two beta-secretase candidates,
      ASP-1 and ASP-2, were identified as aspartic proteases, both of which cleave the
      amyloid precursor at the beta-site. These are produced as immature transmembrane
      proteins containing a pro-segment. RESULTS: ASP-2 expressed in HEK293-cells
      cleaved the Swedish mutant amyloid precursor at different beta-sites at different
      pHs in vitro. Recent reports show that furin cleaves the pro-peptide of ASP-2,
      whereas ASP-1 undergoes auto-catalysis. We show that purified recombinant ASP-2
      cleaves its own pro-peptide at ph 5 but not pH 8.5 as seen by mass spectrometry,
      electrophoresis and N-terminal sequencing. CONCLUSION: We suggest that ASP-2
      processing as well as activity are influenced by pH, and hence the cellular
      localisation of the protein may have profound effects on the production of Abeta.
      These factors should be taken into consideration in the design of potential
      inhibitors for these enzymes.

PMID- 12204095
TI  - Modulation of cathepsin G expression in severe atopic dermatitis following medium
      dose UVA1 phototherapy.
AB  - BACKGROUND: During the last decade, medium-dose UVA1 phototherapy (50 J/cm2) has
      achieved great value within the treatment of severe atopic dermatitis (AD). The
      purpose of our study was to investigate to what extent UVA1 irradiation is able
      to modulate the status of protease activity by the use of a monoclonal antibody
      labeling cathepsin G. METHODS: In order to further elucidate the mechanisms by
      which medium-dose UVA1 irradiation leads to an improvement of skin status in
      patients with AD, biopsy specimens from 15 patients before and after treatment
      were analyzed immunohistochemically for proteolytic activation. RESULTS: Compared
      to lesional skin of patients with AD before UVA1 irradiation, the number of cells
      positive for cathepsin G within the dermal infiltrate decreased significantly
      after treatment. The decrease of cathepsin G+ cells was closely linked to a
      substantial clinical improvement in skin condition. CONCLUSIONS: In summary, our
      findings demonstrated that medium-dose UVA1 irradiation leads to a modulation of
      the expression of cathepsin G in the dermal inflammatory infiltrate in patients
      with severe AD. Cathepsin G may attack laminin, proteoglycans, collagen I and
      insoluble fibronectin, to provoke proinflammatory events, to degrade the basement
      membrane, to destroy the tissue inhibitor of metalloproteinases and to increase
      the endothelial permeability. Therefore, its down-regulation by UVA1 phototherapy
      may induce the reduction of skin inflammation as well as improvement of the skin
      condition.

PMID- 12204096
TI  - Physician perceptions of primary prevention: qualitative base for the conceptual
      shaping of a practice intervention tool.
AB  - BACKGROUND: A practice intervention must have its basis in an understanding of
      the physician and practice to secure its benefit and relevancy. We used a
      formative process to characterize primary care physician attitudes, needs, and
      practice obstacles regarding primary prevention. The characterization will
      provide the conceptual framework for the development of a practice tool to
      facilitate routine delivery of primary preventive care. METHODS: A focus group of
      primary care physician Opinion Leaders was audio-taped, transcribed, and
      qualitatively analyzed to identify emergent themes that described physicians'
      perceptions of prevention in daily practice. RESULTS: The conceptual worth of
      primary prevention, including behavioral counseling, was high, but its practice
      was significantly countered by the predominant clinical emphasis on and rewards
      for secondary care. In addition, lack of health behavior training, perceived low
      self-efficacy, and patient resistance to change were key deterrents to primary
      prevention delivery. Also, the preventive focus in primary care is not on cancer,
      but on predominant chronic nonmalignant conditions. CONCLUSIONS: The success of
      the future practice tool will be largely dependent on its ability to "fit"
      primary prevention into the clinical culture of diagnoses and treatment sustained
      by physicians, patients, and payers. The tool's message output must be formatted
      to facilitate physician delivery of patient-tailored behavioral counseling in an
      accurate, confident, and efficacious manner. Also, the tool's health behavior
      messages should be behavior-specific, not disease-specific, to draw on shared
      risk behaviors of numerous diseases and increase the likelihood of perceived
      salience and utility of the tool in primary care.

PMID- 12204097
TI  - The new middle level health workers training in the Amhara regional state of
      Ethiopia: students' perspective.
AB  - BACKGROUND: Following health sector reform, Ethiopia started training new
      categories of health workers. This study addresses students' perspectives
      regarding their training and career plans. METHODS: A cross sectional
      questionnaire was administered to 145 students in the three schools of the Amhara
      regional state of Ethiopia. RESULTS: The majority of students were male (62%) and
      originally from urban areas (76%). Job search was the most common reason for
      enrolling in the training for almost half (48%) of the respondents, followed by a
      desire to help the sick (46%). Once trained, the majority (98%) of graduates
      preferred to serve in the government sector and in rural health institutions
      (84%). Females were more willing to work in rural settings [chi2 (df 1)= 7.37; P
      = 0.007]. The majority (98%) of students felt the training period should be
      extended. 12% of graduates lacked confidence in their competencies after
      completing the training. A substantial proportion of the respondents (29%) did
      not feel the social science courses (Anthropology, Ecology and Psychology) were
      useful. CONCLUSIONS: This study demonstrates that mid-level health professional
      students are highly motivated, wish to address the health needs of rural
      communities, and are interested in professional development. However, students do
      not feel the training programs are fully addressing their needs. The students
      found that the duration of the training, the time for theory and practice, the
      availability of teaching materials, the course contents and their teachers were
      inadequate. This study suggests that the current training programs have serious
      inadequacies that need to be addressed.

PMID- 12204099
TI  - Investigating the mechanism of acoustically activated uptake of drugs from
      Pluronic micelles.
AB  - BACKGROUND: This paper examines the mechanism of ultrasonic enhanced drug
      delivery from Pluronic micelles. In previous publications by our group,
      fluorescently labeled Pluronic was shown to penetrate HL-60 cells with and
      without the action of ultrasound, while drug uptake was increased with the
      application of ultrasound. METHODS: In this study, the amount of uptake of two
      fluorescent probes, Lysosensor Green (a pH-sensitive probe) and Cell Tracker
      Orange CMTMR (a pH-independent probe), was measured in HL-60 and HeLa cells.
      RESULTS: The results of our experiments show that the increase in drug
      accumulation in the cells as a result of ultrasonication is not due to an
      increase in endocytosis due to ultrasonication. CONCLUSIONS: We hypothesize that
      sonoporation plays an important role in the acoustically activated drug delivery
      of chemotherapy drugs delivered from Pluronic micelles.

PMID- 12204098
TI  - Primary effect of chemotherapy on the transcription profile of AIDS-related
      Kaposi's sarcoma.
AB  - BACKGROUND: Drugs & used in anticancer chemotherapy have severe effects upon the
      cellular transcription and replication machinery. From in vitro studies it has
      become clear that these drugs can affect specific genes, as well as have an
      effect upon the total transcriptome. METHODS: Total mRNA from two skin lesions
      from a single AIDS-KS patient was analyzed with the SAGE (Serial Analysis of Gene
      Expression) technique to assess changes in the transcriptome induced by
      chemotherapy. SAGE libraries were constructed from material obtained 24 (KS-24)
      and 48 (KS-48) hrs after combination therapy with bleomycin, doxorubicin and
      vincristine. KS-24 and KS-48 were compared to SAGE libraries of untreated AIDS
      KS, and to libraries generated from normal skin and from isolated CD4+ T-cells,
      using the programs USAGE and HTM. SAGE libraries were also compared with the
      SAGEmap database. RESULTS: In order to assess the primary response of AIDS
      related Kaposi's sarcoma (AIDS-KS) to chemotherapy in vivo, we analyzed the
      transcriptome of AIDS-KS skin lesions from a HIV-1 seropositive patient at two
      time points after therapy. The mRNA profile was found to have changed
      dramatically within 24 hours after drug treatment. There was an almost complete
      absence of transcripts highly expressed in AIDS-KS, probably due to a
      transcription block. Analysis of KS-24 suggested that mRNA pool used in its
      construction originated from poly(A) binding protein (PABP) mRNP complexes, which
      are probably located in nuclear structures known as interchromatin granule
      clusters (IGCs). IGCs are known to fuse after transcription inhibition, probably
      affecting poly(A)+RNA distribution.Forty-eight hours after chemotherapy, mRNA
      isolated from the lesion was largely derived from infiltrating lymphocytes,
      confirming the transcriptional block in the AIDS-KS tissue. CONCLUSIONS: These in
      vivo findings indicate that the effect of anti-cancer drugs is likely to be more
      global than up- or downregulation of specific genes, at least in this single
      patient with AIDS-KS. The SAGE results obtained 24 hrs after chemotherapy can be
      most plausibly explained by the isolation of a fraction of more stable
      poly(A)+RNA.

PMID- 12204100
TI  - Computational method for reducing variance with Affymetrix microarrays.
AB  - BACKGROUND: Affymetrix microarrays are used by many laboratories to generate gene
      expression profiles. Generally, only large differences (> 1.7-fold) between
      conditions have been reported. Computational methods to reduce inter-array
      variability might be of value when attempting to detect smaller differences. We
      examined whether inter-array variability could be reduced by using data based on
      the Affymetrix algorithm for pairwise comparisons between arrays (ratio method)
      rather than data based on the algorithm for analysis of individual arrays (signal
      method). Six HG-U95A arrays that probed mRNA from young (21-31 yr old) human
      muscle were compared with six arrays that probed mRNA from older (62-77 yr old)
      muscle. RESULTS: Differences in mean expression levels of young and old subjects
      were small, rarely > 1.5-fold. The mean within-group coefficient of variation for
      4629 mRNAs expressed in muscle was 20% according to the ratio method and 25%
      according to the signal method. The ratio method yielded more differences
      according to t-tests (124 vs. 98 differences at P < 0.01), rank sum tests (107
      vs. 85 differences at P < 0.01), and the Significance Analysis of Microarrays
      method (124 vs. 56 differences with false detection rate < 20%; 20 vs. 0
      differences with false detection rate < 5%). The ratio method also improved
      consistency between results of the initial scan and results of the antibody
      enhanced scan. CONCLUSION: The ratio method reduces inter-array variance and
      thereby enhances statistical power.

PMID- 12204101
TI  - Mechanism of cigarette smoke condensate-induced acute inflammatory response in
      human bronchial epithelial cells.
AB  - BACKGROUND: To demonstrate the involvement of tobacco smoking in the
      pathophysiology of lung disease, the responses of pulmonary epithelial cells to
      cigarette smoke condensate (CSC) - the particulate fraction of tobacco smoke -
      were examined. METHODS: The human alveolar epithelial cell line A549 and normal
      human bronchial epithelial cells (NHBEs) were exposed to 0.4 microg/ml CSC, a
      concentration that resulted in >90% cell survival and <5% apoptosis. Changes in
      gene expression and signaling responses were determined by RT-PCR, western
      blotting and immunocytofluorescence. RESULTS: NHBEs exposed to CSC showed
      increased expression of the inflammatory mediators sICAM-1, IL-1beta, IL-8 and GM
      CSF, as determined by RT-PCR. CSC-induced IL-1beta expression was reduced by
      PD98059, a blocker of mitogen-actived protein kinase (MAPK) kinase (MEK), and by
      PDTC, a NFkappaB inhibitor. Analysis of intracellular signaling pathways, using
      antibodies specific for phosphorylated MAPKs (extracellular signal-regulated
      kinase [ERK]-1/2), demonstrated an increased level of phosphorylated ERK1/2 with
      increasing CSC concentration. Nuclear localization of phosphorylated ERK1/2 was
      seen within 30 min of CSC exposure and was inhibited by PD98059. Increased
      phosphorylation and nuclear translocation of IkappaB was also seen after CSC
      exposure. A549 cells transfected with a luciferase reporter plasmid containing a
      NFkappaB-inducible promoter sequence and exposed to CSC (0.4 microg/ml) or TNF
      alpha (50 ng/ml) had an increased reporter activity of approximately 2-fold for
      CSC and 3.5-fold for TNF-alpha relative to untreated controls. CONCLUSION: The
      acute phase response of NHBEs to cigarette smoke involves activation of both MAPK
      and NFkappaB.

PMID- 12204102
TI  - Activation of adherent vascular neutrophils in the lung during acute endotoxemia.
AB  - BACKGROUND: Neutrophils constitute the first line of defense against invading
      microorganisms. Whereas these cells readily undergo apoptosis under homeostatic
      conditions, their survival is prolonged during inflammatory reactions and they
      become biochemically and functionally activated. In the present study, we
      analyzed the effects of acute endotoxemia on the response of a unique
      subpopulation of neutrophils tightly adhered to the lung vasculature. METHODS:
      Rats were treated with 5 mg/kg lipopolysaccharide (i.v.) to induce acute
      endotoxemia. Adherent neutrophils were isolated from the lung vasculature by
      collagenase digestion and sequential filtering. Agarose gel electrophoresis, RT
      PCR, western blotting and electrophoretic mobility shift assays were used to
      evaluate neutrophil activity. RESULTS: Adherent vascular neutrophils isolated
      from endotoxemic animals exhibited decreased apoptosis when compared to cells
      from control animals. This was associated with a marked increase in expression of
      the anti-apoptotic protein, Mcl-1. Cells isolated 0.5-2 hours after endotoxin
      administration were more chemotactic than cells from control animals and
      expressed increased tumor necrosis factor-alpha and cyclooxygenase-2 mRNA and
      protein, demonstrating that they are functionally activated. Endotoxin treatment
      of the animals also induced p38 and p44/42 mitogen activated protein kinases in
      the adherent lung neutrophils, as well as nuclear binding activity of the
      transcription factors, NF-kappaB and cAMP response element binding protein.
      CONCLUSION: These data demonstrate that adherent vascular lung neutrophils are
      highly responsive to endotoxin and that pathways regulating apoptosis and
      cellular activation are upregulated in these cells.

PMID- 12204104
TI  - Midkine and pleiotrophin: two related proteins involved in development, survival,
      inflammation and tumorigenesis.
AB  - Midkine (MK) and pleiotrophin (PTN) are low molecular weight proteins with
      closely related structures. They are mainly composed of two domains held by
      disulfide bridges, and there are three antiparallel beta-sheets in each domain.
      MK and PTN promote the growth, survival, and migration of various cells, and play
      roles in neurogenesis and epithelial mesenchymal interactions during
      organogenesis. A chondroitin sulfate proteoglycan, protein-tyrosine phosphatase
      zeta (PTPzeta), is a receptor for MK and PTN. The downstream signaling system
      includes ERK and PI3 kinase. MK binds to the chondroitin sulfate portion of
      PTPzeta with high affinity. Among the various chondroitin sulfate structures, the
      E unit, which has 4,6-disulfated N-acetylgalactosamine, provides the strongest
      binding site. The expression of MK and PTN is increased in various human tumors,
      making them promising as tumor markers and as targets for tumor therapy. MK and
      PTN expression also increases upon ischemic injury. MK enhances the migration of
      inflammatory cells, and is involved in neointima formation and renal injury
      following ischemia. MK is also interesting from the viewpoints of the treatment
      of neurodegenerative diseases, increasing the efficiency of in vitro development,
      and the prevention of HIV infection.

PMID- 12204103
TI  - Distinct signal transduction processes by IL-4 and IL-13 and influences from the
      Q551R variant of the human IL-4 receptor alpha chain.
AB  - BACKGROUND: Although IL-4 and IL-13 share the IL-13 receptor, IL-13 exhibits
      unique functions. To elicit the cellular basis of these differences, signal
      transduction processes have been compared. Additionally, the role of the IL-4
      receptor alpha (IL-4Ralpha) variant Q551R was investigated. METHODS: Peripheral
      blood mononuclear cells from donors were stimulated with IL-4 and IL-13. The
      phosphorylation status of effector substrates was detected by immunostaining.
      Binding of SHP-2 to IL-4Ralpha was investigated by using synthetic peptides.
      RESULTS: SHP-2 bound IL-4Ralpha synthetic peptide; this binding was reduced in
      the presence of the R551 variant. Stimulation with IL-4 increased SHP-1
      phosphorylation, however, stimulation with IL-13 increased SHP-2 phosphorylation.
      PI3-kinase phosphorylation was elevated following stimulation with IL-13 in all
      individuals and with IL-4 only in R551 individuals. Jak1, Tyk2 and IRS-2 signals
      were reduced after IL-13 stimulation in Q551 individuals. STAT3 phosphorylation
      was markedly increased in R551 individuals, following stimulation with both IL-4
      and IL-13. However, STAT3 was only detected immediately in nuclear extracts from
      variant individuals after stimulation with IL-13; in wildtype individuals STAT3
      was only detected after IL-4 treatment. CONCLUSION: IL-4 and IL-13 appear to
      promote distinct signal transduction cascades. SHP-1 seems to be predominately
      activated by IL-4 and to influence the PI3-kinase, in contrast, SHP-2 seems to be
      predominately activated by IL-13 and to influence Jak1, Tyk2 and IRS-2. Both
      phosphatases control STAT3. In the presence of the variant R551, SHP-1/2
      activation is reduced and signal transduction is altered. STAT3 signaling appears
      be further regulated on the level of nuclear translocation.

PMID- 12204105
TI  - Type I collagen inhibits hydroxyl radical-induced apoptosis.
AB  - The extracellular matrix (ECM) plays an important role in cell differentiation
      and apoptosis. Collagen is the major component of ECM. Here, an ESR signal of the
      hydroxyl radicals (.OH) generated via Fe2+ -mediated Fenton reaction was found to
      be significantly inhibited by type I collagen. Further study showed that type I
      collagen also inhibited cell apoptosis induced by.OH, as evidenced by
      morphological criteria (DAPI and annexin V staining) and quantitive assays for
      apoptotic cells (MTT and flow-cytometric assay for subG1 cells). By addition of
      type I collagen in HeLa cells, the lipid peroxidation caused by.OH was inhibited
      and the cellular GSH was protected. In comparison with type I collagen, BSA and
      the denatured collagen, gelatin, lacked such antioxidative and antiapoptotic
      effects. Together, the results suggest that type I collagen can uniquely
      prevent.OH-mediated apoptosis by scavenging free radicals.

PMID- 12204106
TI  - Independence of plasma membrane blebbing from other biochemical and biological
      characteristics of apoptotic cells.
AB  - Plasma membrane blebs are observed in many types of apoptotic cells, but their
      physiological roles remain to be clarified. We examined whether there is a
      causative connection between membrane blebbing and other apoptotic changes in
      Jurkat cells induced to undergo apoptosis by doxorubicin in the presence or
      absence of Y-27632, an inhibitor of the Rho kinase ROCK-I. The inclusion of the
      drug made most membrane blebs disappear, while other changes, such as chromatin
      condensation, inactivation of mitochondrial enzymes, externalization of the
      membrane phospholipid phosphatidylserine, and removal of cell surface sialic
      acid, remained unaffected. Furthermore, these apoptotic cells were phagocytosed
      by macrophages as efficiently as normally apoptosing cells. These results
      indicate that blebbing of the plasma membrane occurs independently from other
      apoptotic changes and is not involved in the recognition and engulfment of
      apoptotic cells by macrophages.

PMID- 12204107
TI  - Phylogenetic development of a regulatory gene for the core 2 GlcNAc transferase
      in Mus musculus.
AB  - In our previous study, we identified a mouse gene, Gsl5, that controls the
      expression of a glycolipid, GL-Y [Galbeta1-4(Fucalpha1-3)GlcNAcbeta1-6(Galbeta1
      3)GalNAcbeta1-3Galalpha1-4Galbeta1-4Glcbeta1-Cer], and the core 2 structure of O
      linked glycans of glycoproteins, GlcNAcbeta1-6(Galbeta1-3)GalNAcalpha-Ser/Thr, in
      a kidney tubular cell-specific manner through the regulation of UDP-GlcNAc beta
      1,6-GlcNAc transferase (GNT). Regulation by the Gsl5 gene occurs at the level of
      GNT mRNA and the recessive allele of Gsl5 is rare and carried by DBA/2 and its
      related strains. Here, we report a sequence comparison of the 5' flanking region
      of the GNT gene among 5 laboratory strains and 10 wild-derived strains,
      demonstrating that the DBA/2 allele sequence is similar to the sequence carried
      by Asian Mus m. musculus and differs substantially from the East European M. m.
      musculus. These results suggest that the DBA/2 allele of Gsl5 was introduced into
      laboratory mouse strains by Asian wild-derived mice. Phylogenetic comparison of
      the 5' flanking region sequences between the recessive and dominant Gsl5 alleles
      indicates that mutations to create a functional Gsl5 gene occurred approximately
      one million years ago during the subspeciation of M. musculus, and provides a
      case for studies on the creation of functional genes involved in tissue-specific
      transcriptional regulation.

PMID- 12204108
TI  - Effects of pravastatin sodium on mevalonate metabolism in common marmosets.
AB  - In experimental animals and humans, the concentration of serum mevalonate (MVA),
      a direct product of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, is
      considered to reflect the activity of whole-body sterol synthesis. The
      relationship between the concentration of serum MVA and the activity of sterol
      synthesis in tissues, however, has not been fully clarified. In the present
      study, we examined MVA metabolism by using pravastatin, a liver-selective
      inhibitor of HMG-CoA reductase, and common marmosets, a good model animal for
      studying lipid metabolism. In the time course study, the maximal reduction in the
      concentration of serum MVA was observed 2 h after a single oral administration of
      30 mg/kg pravastatin to common marmosets. We, therefore, examined the
      relationship between the concentrations of serum and hepatic MVA, and sterol
      synthesis in some tissues at this time point. Sterol synthesis was determined ex
      vivo in tissue slices by measuring the incorporation of [14C]acetate into
      digitonin-precipitable [14C]sterols. Pravastatin at 0.03-30 mg/kg reduced dose
      dependently the activity of hepatic sterol synthesis, whereas no significant
      reduction of sterol synthesis was observed in other tissues such as intestine,
      kidney, testis and spleen, even with the highest dose (30 mg/kg). The liver
      specific inhibition of sterol synthesis caused parallel reductions in the
      concentrations of both serum and liver MVA. In addition, there were good
      correlations between the concentration of either serum or hepatic MVA and the
      activity of hepatic sterol synthesis. These data indicate that the major origin
      of serum MVA is the liver, and that the concentration of serum MVA reflects the
      concentration of hepatic MVA and the activity of hepatic sterol synthesis 2 h
      after a single oral administration of pravastatin in common marmosets.

PMID- 12204109
TI  - The chaperone activity of protein disulfide isomerase is affected by cyclophilin
      B and cyclosporin A in vitro.
AB  - To elucidate the function of protein disulfide isomerase (PDI), we screened for
      PDI-binding proteins in a bovine liver extract using affinity column
      chromatography. One of the binding proteins was identified by SDS-PAGE and N
      terminal amino acid sequence analysis to be cyclophilin B (Cyp B). Use of the
      BIACORE system revealed that purified bovine Cyp B bound specifically to bovine
      PDI with a K(D) value of 1.19 x 10(-5) M. Interestingly, the binding affinity
      between PDI and Cyp B was strengthened by preincubation of the Cyp B with
      cyclosporin A (CsA), yielding a K(D) value of 3.67 x 10(-6) M. Although the
      interaction between PDI and Cyp B affected neither the isomerase activity of PDI
      nor the peptidyl-prolyl cis-trans isomerase activity of Cyp B, Cyp B increased
      the chaperone activity of PDI. However, the complex of Cyp B and CsA completely
      inhibited the chaperone activity of PDI. Thus, PDI and Cyp B appear to cooperate
      with each other to regulate the functional expression of proteins in vivo.

PMID- 12204110
TI  - Epitope distribution of randomly established monoclonal antibodies against human
      type II DNA topoisomerases.
AB  - The epitopes of about 100 monoclonal antibodies against human type II DNA
      topoisomerase were mapped along the enzyme molecules. Although they were randomly
      and independently established, epitope sites were unevenly distributed the toward
      N-terminal or C-terminal region. We suggest that the central catalytic domain is
      hidden inside the molecule and inaccessible to the antigen recognition sites.
      Using antibodies, we demonstrate the distinct localization of isoforms of Topo II
      in cultured cells. Some particularly useful antibodies are listed.

PMID- 12204111
TI  - Myonase is localized in skeletal muscle myofibrils.
AB  - A novel chymotrypsin-like proteinase termed myonase was previously purified from
      MDX-mouse skeletal muscle [Hori et al. (1998) J. Biochem. 123, 650-658]. Western
      blots and immunohistochemical analyses showed that myonase was present within
      myocytes of both MDX-mouse and control mouse, and subcellular fractionation
      showed that it was associated with myofibrils. No significant difference was
      observed on Western blots between the amounts of myonase in myofibrils of MDX
      mouse and control mouse, but the amount of myonase recoverable as a pure protein
      was 5-10-fold more when MDX-mouse was the source of the skeletal muscle.
      Myofibrils also possessed an endogenous inhibitor of myonase, whose inhibitory
      activity at physiological pH (pH 7.4) depended on salt concentration, stronger
      inhibition being observed at a low salt concentration. Inhibition at alkaline pH
      (pH 9) was weak and independent of salt concentration. Myonase in myofibrils was
      partially released at neutral pH by a high salt concentration (>0.6 M NaCl).
      However, even at 4 M NaCl, more than 80% of myonase remained within the
      myofibrils. Under alkaline conditions, release of myonase from myofibril was more
      extensive. At pH 12, myonase was almost completely present in the soluble
      fraction. Release of myonase under these conditions coincided with the
      solubilization of other myofibrillar proteins.

PMID- 12204112
TI  - Expression of the oxidative stress-regulated transcription factor bach2 in
      differentiating neuronal cells.
AB  - Bach2 is an oxidative stress-regulated transcription factor and functions as a
      repressor of gene expression directed by the TPA-response element, the Maf
      recognition element, and the antioxidant responsive element. To investigate the
      possibility that these enhancers are regulated in a tissue-specific manner, we
      analyzed expression of Bach2 during differentiation of neural cells. Bach2 was
      induced upon neuronal differentiation of P19 embryonic carcinoma cells, while its
      related factor Bach1 did not show significant change. By using affinity-purified
      anti-Bach2 antibodies, expression of Bach2 in mouse embryos was determined. High
      levels of Bach2 antigen were found in differentiating neuronal and lens cells in
      day 12.5 embryos. Consistent with the fact that subcellular localization of Bach2
      is regulated by nuclear export in cultured cells, extensive Bach2-staining was
      found in the cytoplasmic regions of developing neuronal and lens cells. These
      results suggest that Bach2 regulates AP-1- and Maf-dependent gene expression
      during development of neuronal and lens cells and that its activity may be
      regulated by nuclear export in these cells.

PMID- 12204113
TI  - Spectroscopic analysis of recombinant rat histidine decarboxylase.
AB  - Mammalian histidine decarboxylases have not been characterized well owing to
      their low amounts in tissues and instability. We describe here the first
      spectroscopic characterization of a mammalian histidine decarboxylase, i.e. a
      recombinant version of the rat enzyme purified from transformed Escherichia coli
      cultures, with similar kinetic constants to those reported for mammalian
      histidine decarboxylases purified from native sources. We analyzed the
      absorption, fluorescence and circular dichroism spectra of the enzyme and its
      complexes with the substrate and substrate analogues. The pyridoxal-5'-phosphate
      enzyme internal Schiff base is mainly in an enolimine tautomeric form, suggesting
      an apolar environment around the coenzyme. Michaelis complex formation leads to a
      polarized, ketoenamine form of the Schiff base. After transaldimination, the
      coenzyme-substrate Schiff base exists mainly as an unprotonated aldimine, like
      that observed for dopa decarboxylase. However, the coenzyme-substrate Schiff base
      suffers greater torsion than that observed in other L-amino acid decarboxylases,
      which may explain the relatively low catalytic efficiency of this enzyme. The
      active center is more resistant to the formation of substituted aldamines than
      the prokaryotic homologous enzyme and other L-amino acid decarboxylases.
      Characterization of the similarities and differences of mammalian histidine
      decarboxylase with respect to other homologous enzymes would open new
      perspectives for the development of new and more specific inhibitors with
      pharmacological potential.

PMID- 12204114
TI  - Resistance against ricin-induced apoptosis in a brefeldin A-resistant mutant cell
      line (BER-40) of Vero cells.
AB  - We have found that a brefeldin A (BFA)-resistant mutant cell line derived from
      Vero cells (BER-40) is highly resistant to ricin-induced apoptosis as compared
      with parental Vero cells. In BER-40 cells, all apoptotic events caused by ricin
      including cytolysis, nuclear morphological changes, and DNA fragmentation occur
      to a lesser extent than in Vero cells, even though both cell lines show similar
      sensitivities to ricin-mediated inhibition of protein synthesis. Furthermore, no
      significant apoptotic signaling events, such as increases in caspase-3 and -9
      like activities, release of cytochrome c from mitochondria, or the cleavage of
      PARP, were observed in BER-40 cells under the conditions at which these changes
      were evident in Vero cells. Intracellular biochemical changes associated with
      ricin-induced apoptosis, such as the depletion of glutathione and an increase in
      free Zn2+, were also less apparent in BER-40 cells than in Vero cells. BER-40
      cells were also found to be highly resistant to apoptosis induced by other toxins
      with different intoxication mechanisms such as diphtheria toxin, modeccin, and
      anisomycin. These results suggest that the entire apoptotic signal transduction
      mechanism in BER-40 cells, which may be triggered after the inhibition of protein
      synthesis by toxins, becomes resistant. Since MDCK cells, a naturally BFA
      resistant cell line, are highly sensitive to ricin-induced apoptosis, it seems
      likely that the BFA resistance phenotype may not necessarily lead to resistance
      to apoptotic cell death. Probably the underlaying BFA-resistance mechanism in BER
      40 cells is distinct from that in MDCK cells, and the resistance to ricin-induced
      apoptosis of BER-40 cells may be a unique phenotype acquired concomitantly with
      BFA-resistance.

PMID- 12204115
TI  - Functional analysis of human P5, a protein disulfide isomerase homologue.
AB  - Human P5 (hP5) was expressed in the Escherichia coli pET system and purified by
      sequential Ni(2+)-chelating resin column chromatography. Characterization of
      purified hP5 indicated that it has both isomerase and chaperone activities, but
      both activities are lower than those of human protein disulfide isomerase (PDI).
      Moreover, hP5 was observed to have peptide-binding ability, and its chaperone
      activity was confirmed with rhodanese and citrate synthase as substrates, but not
      with D-glyceraldehyde-3-phosphate dehydrogenase, showing that hP5 has substrate
      specificity with respect to chaperone activity. Mutation of two thioredoxin
      related motifs in hP5 revealed that the first motif is more important than the
      second for isomerase activity and that the first cysteine in each motif is
      necessary for isomerase activity. Since thioredoxin motif mutants lacking
      isomerase activity retain chaperone activity with the substrate citrate synthase,
      the isomerase and chaperone activities of hP5 are probably independent, as was
      shown for PDI.

PMID- 12204116
TI  - Regulatory effects of divalent metal cations on human cytosolic
      sulfotransferases.
AB  - Cytosolic sulfotransferases (STs), traditionally viewed as Phase II drug
      metabolizing or detoxifying enzymes, are increasingly being implicated in the
      metabolism of endogenous biologically-active molecules. Except for studies on
      changes in their levels of expression and activity in the early stage of
      development in mammals, very little is known about how these enzymes are
      regulated. In this study, the regulatory effects of divalent metal cations on the
      activity of human cytosolic STs were quantitatively evaluated. Results obtained
      indicate that all nine human cytosolic STs examined are partially or completely
      inhibited/stimulated by the ten divalent metal cations tested at 10 mM
      concentration. Compared with the other metal cations, the inhibitory or
      stimulatory effect of Mg2+ and Ca2+ on the activities of the human cytosolic STs
      appeared to be relatively smaller. Concentration-dependent effects of the
      divalent metal cations were further examined. The IC50 or EC50 values determined
      for different divalent metal cations were mostly above their normal physiological
      concentration ranges. In a few cases, however, IC50 values close to the
      physiological concentrations of certain divalent metal cations were observed.
      Using the monoamine (M)-form phenol ST (PST) as a model, it was demonstrated that
      the K(m) for dopamine changed only slightly with increasing concentrations of
      Cd2+, whereas the V(max) was dramatically decreased.

PMID- 12204117
TI  - A novel low-molecular-mass dual-specificity phosphatase, LDP-2, with a naturally
      occurring substitution that affects substrate specificity.
AB  - We have identified a novel dual-specificity phosphatase (DSP), called LDP-2 (low
      molecular-mass DSP-2), composed of 220 amino acid residues showing high sequence
      homology to VHR and LDP-1/TMDP, which belong to a family of DSPs with low
      molecular masses. The LDP-2 gene is ubiquitously expressed, and LDP-2 is
      localized in the cytoplasm. The main structural feature of LDP-2 is that the
      serine-156 residue located in the common active site sequence motif, HCXXGXXRS,
      for DSP is naturally substituted with an alanine residue. The recombinant LDP-2
      protein showed extremely low phosphatase activity towards p-nitrophenyl phosphate
      (pNPP). Back-mutation of Ala-156 in LDP-2 to a serine (A156S mutation) conferred
      significant phosphatase activity towards pNPP. However, both LDP-2 and LDP-2
      (A156S) exhibited substantial phosphatase activities towards both phospho
      seryl/threonyl and -tyrosyl residues of myelin basic protein, with similar
      specific activities. Ala-156 of LDP-2 might be crucially involved in the
      recognition of a physiological substrate. We analyzed the effect of VHR and LDP-2
      on mitogen-activated protein kinases (MAPKs) in vivo. We first found that VHR
      inhibits the activation of p38 as well as ERK and JNK, with similar efficiency.
      Under the conditions used, LDP-2 specifically suppressed JNK activation.

PMID- 12204118
TI  - Analysis of the conformational change of myosin during ATP hydrolysis using
      fluorescence resonance energy transfer.
AB  - In order to elucidate the molecular basis of energy transduction by myosin as a
      molecular motor, a fluorescent ribose-modified ATP analog 2'(3')-O-[6-(N-(7
      nitrobenz-2-oxa-1,3-diazol-4-yl)amino)hexanoyl]-ATP (NBD-ATP), was utilized to
      study the conformational change of the myosin motor domain during ATP hydrolysis
      using the fluorescence resonance energy transfer (FRET) method. The FRET
      efficiency from the fluorescent probe, BD- or AD-labeled at the reactive cysteine
      residues, SH1 (Cys 707) or SH2 (Cys697), respectively, to the NBD fluorophore in
      the ATP binding site was measured for several transient intermediates in the
      ATPase cycle. The FRET efficiency was greater than that using NBD-ADP. The FRETs
      for the myosin.ADP.AlF4- and myosin.ADP.BeFn ternary complexes, which mimic the
      M*.ADP.P(i) state and M.ATP state in the ATPase cycle, respectively, were similar
      to that of NBD-ATP. This suggests that both the SH1 and SH2 regions change their
      localized conformations to move closer to the ATPase site in the M*.ATP state and
      M**.ADP.P(i) state than in the M*.ADP state. Furthermore, we measured energy
      transfer from BD in the essential light chain to NBD in the active site. Assuming
      the efficiency at different states, myosin adopts a conformation such that the
      light chain moves closer to the active site by approximately 9 A during the
      hydrolysis of ATP.

PMID- 12204119
TI  - KIF1Bbeta2, capable of interacting with CHP, is localized to synaptic vesicles.
AB  - Kinesin family proteins are microtubule-dependent molecular motors involved in
      the intracellular motile process. Using a Ca2+ -binding protein, CHP (calcineurin
      B homologous protein), as a bait for yeast two hybrid screening, we identified a
      novel kinesin-related protein, KIF1Bbeta2. KIF1Bbeta2 is a member of the KIF1
      subfamily of kinesin-related proteins, and consists of an amino terminal KIF1B
      type motor domain followed by a tail region highly similar to that of KIF1A. CHP
      binds to regions adjacent to the motor domains of KIF1Bbeta2 and KIF1B, but not
      to those of the other KIF1 family members, KIF1A and KIF1C. Immunostaining of
      neuronal cells showed that a significant portion of KIF1Bbeta2 is co-localized
      with synaptophysin, a marker protein for synaptic vesicles, but not with a
      mitochondria-staining dye. Subcellular fractionation analysis indicated the co
      localization of KIF1Bbeta2 with synaptophysin. These results suggest that
      KIF1Bbeta2, a novel CHP-interacting molecular motor, mediates the transport of
      synaptic vesicles in neuronal cells.

PMID- 12204120
TI  - Mutational analysis of residues in two consensus motifs in the active sites of
      cathepsin E.
AB  - Cathepsin E, an intracellular aspartic proteinase of the pepsin family, is
      composed of two homologous domains, each containing the catalytic Asp residue in
      a consensus DTG motif. Here we examine the significance of residues in the motifs
      of rat cathepsin E by substitution of Asp98, Asp283, and Thr284 with other
      residues using site-directed mutagenesis. Each of the mutant proenzymes, as well
      as the wild-type protein, was found in culture media and cell extracts when
      heterologously expressed in human embryonic kidney 293T cells. The single mutants
      D98A, D283A, and D283E, and the double mutants D98A/D283A and D98E/D283E showed
      neither autocatalytic processing nor enzymatic activities under acidic
      conditions. However, the D98E and T284S mutants retained the ability to transform
      into the mature forms, although they exhibited only about 13 and 40% of the
      activity of the wild-type enzyme, respectively. The K(m) values of these two
      mutants were similar to those of the wild-type enzyme, but their k(cat) values
      were greatly decreased. The K(i) values for pepstatin and the Ascaris pepsin
      inhibitor of the mutants and the wild-type enzyme were almost the same. The
      circular dichroism spectra of the two mutants were essentially the same as those
      of the wild-type enzyme at various pH values. These results indicate that (i)
      Asp98, Asp283, and Thr284 are indeed critical for catalysis, and (ii) the
      decrease in the catalytic activity of D98E and T284S mutants is brought about by
      an effect on the kinetic process from the enzyme-substrate complex to the release
      of the product.

PMID- 12204121
TI  - Downregulation of urokinase-type and tissue-type plasminogen activators in a
      rabbit model of renal ischemia/reperfusion.
AB  - Urokinase-type and tissue-type plasminogen activators (uPA, tPA) are key enzymes
      for starting the plasminogen system, which plays important roles in various
      physiological and pathological conditions. In order to examine the gene
      regulation in rabbit pathophysiological models we attempted to clone full-length
      cDNAs encoding uPA and tPA from kidney extracts of rabbit (Oryctolagus cuniculus)
      by reverse transcription-polymerase chain reaction and rapid amplification of
      cDNA ends. The cloned rabbit uPA and tPA cDNAs were 2,350 and 2,561 bp in length,
      respectively, and the basic molecular structures predicted from the cDNAs were
      well-conserved compared with human uPA and tPA. In a rabbit model of renal
      ischemia/reperfusion (I/R), the expression of uPA and tPA mRNAs was down
      regulated and that of their physiological inhibitor, type 1 plasminogen activator
      inhibitor, mRNA was up-regulated in ischemic kidney compared to non-ischemic
      kidney. In addition, fibrinolytic activity in ischemic kidney was lower than that
      in non-ischemic kidney. It is suggested that repression of fibrinolysis in the
      kidneys in rabbit I/R may contribute to the progression of renal damage in the
      model.

PMID- 12204122
TI  - Supine behaviour predicts the time to death in male Mediterranean fruitflies
      (Ceratitis capitata).
AB  - Over 97% of the 203 male medflies monitored in a lifetime study of their
      behaviour exhibited what we term supine behaviour (temporary upside-down
      orientation) starting an average of 16.1 days prior to their death (mean lifespan
      of 61.7 days). Supine onset increased the mortality risk by 39.5-fold and a unit
      increase in supine level increased mortality by 26.3%. The discovery that
      behavioural traits in insects can be used as biomarkers of their health and to
      predict their time to death has important implications regarding research on
      morbidity dynamics, behavioural neuroethology and gerontology, and the
      interpretation of longevity extension in model organisms.

PMID- 12204123
TI  - A role for phenotypic plasticity in the evolution of aposematism.
AB  - The evolution of warning coloration (aposematism) has been difficult to explain
      because rare conspicuous mutants should suffer a higher cost of discovery by
      predators relative to the cryptic majority, while at frequencies too low to
      facilitate predator aversion learning. Traditional models for the evolution of
      aposematism have assumed conspicuous prey phenotypes to be genetically determined
      and constitutive. By contrast, we have recently come to understand that warning
      coloration can be environmentally determined and mediated by local prey density,
      thereby reducing the initial costs of conspicuousness. The expression of density
      dependent colour polyphenism is widespread among the insects and may provide an
      alternative pathway for the evolution of constitutive aposematic phenotypes in
      unpalatable prey by providing a protected intermediate stage. If density
      dependent aposematism can function as an adaptive intermediate stage for the
      evolution of constitutive aposematic phenotypes, differential reaction norm
      evolution is predicted among related palatable and unpalatable prey populations.
      Here, I present empirical evidence that indicates that (i) the expression of
      density-dependent colour polyphenism has differentially evolved between palatable
      and unpalatable populations of the grasshopper Schistocerca emarginata (=
      lineata) (Orthoptera: Acrididae), and (ii) variation in plasticity between these
      populations is commensurate with the expected costs of conspicuousness.

PMID- 12204124
TI  - The distribution of cultural and biological diversity in Africa.
AB  - Anthropologists, biologists and linguists have all noted an apparent coincidence
      in species diversity and human cultural or linguistic diversity. We present, to
      our knowledge, one of the first quantitative descriptions of this coincidence and
      show that, for 2 degrees x 2 degrees grid cells across sub-Saharan Africa,
      cultural diversity and vertebrate species diversity exhibit marked similarities
      in their overall distribution. In addition, we show that 71% of the observed
      variation in species richness and 36% in language richness can be explained on
      the basis of environmental factors, suggesting that similar factors, especially
      those associated with rainfall and productivity, affect the distributions of both
      species and languages. Nevertheless, the form of the relationships between
      species richness and language richness and environmental factors differs, and it
      is unlikely that comparable mechanisms underpin the similar patterns of species
      and language richness. Moreover, the fact that the environmental factors
      considered here explain less than half of the variation in language richness
      indicates that other factors, many of which are likely to be historical or
      social, also influence the distribution of languages.

PMID- 12204125
TI  - The breeding biology of lemon sharks at a tropical nursery lagoon.
AB  - Surprisingly little is known about the reproductive behaviour and breeding
      biology of most shark species, especially in natural populations. Here, we
      characterize reproductive patterns and use of a natal nursery at Bimini, Bahamas
      by lemon sharks, Negaprion brevirostris. We systematically and exhaustively
      sampled young lemon sharks at Bimini annually from 1995 to 2000 and
      opportunistically sampled adults over the same period. Out of the 897 young
      sharks sampled, 119 could be assigned to five sampled mothers using
      microsatellite genotyping. Reproductive females showed strong philopatry to the
      nursery, returning to Bimini every two years to give birth. Each of these females
      may rely entirely on the Bimini nursery for recruitment. The protection of known
      nursery grounds should therefore figure prominently in conservation efforts for
      large coastal shark species. The reconstruction of paternal genotypes indicates
      that litters are sired by multiple males, and females mate with different males
      nearly every breeding cycle. The ubiquitous polyandry reported here raises the
      possibility that genetic incompatibility and post-copulatory paternity-biasing
      mechanisms may operate in viviparous sharks.

PMID- 12204126
TI  - Non-indigenous brook trout and the demise of Pacific salmon: a forgotten threat?
AB  - Non-indigenous species may be the most severe environmental threat the world now
      faces. Fishes, in particular, have been intentionally introduced worldwide and
      have commonly caused the local extinction of native fish. Despite their
      importance, the impact of introduced fishes on threatened populations of Pacific
      salmon has never been systemically examined. Here, we take advantage of several
      unique datasets from the Columbia River Basin to address the impact of non
      indigenous brook trout, Salvelinus fontinalis, on threatened spring/summer-run
      chinook salmon, Oncorhynchus tshawytscha. More than 41 000 juvenile chinook were
      individually marked, and their survival in streams without brook trout was nearly
      double the survival in streams with brook trout. Furthermore, when brook trout
      were absent, habitat quality was positively associated with chinook survival, but
      when brook trout were present no relationship between chinook survival and
      habitat quality was evident. The difference in juvenile chinook survival between
      sites with, and without, brook trout would increase population growth rate
      (lambda) by ca. 2.5%. This increase in lambda would be sufficient to reverse the
      negative population growth observed in many chinook populations. Because many of
      the populations we investigated occur in wilderness areas, their habitat has been
      considered pristine; however, our results emphasize that non-indigenous species
      are present and may have a dramatic impact, even in remote regions that otherwise
      appear pristine.

PMID- 12204127
TI  - Inferring the phylogeny of disjunct populations of the azure-winged magpie
      Cyanopica cyanus from mitochondrial control region sequences.
AB  - The azure-winged magpie (AWM), Cyanopica cyanus, is found in Asia and Iberia.
      This remarkable disjunct distribution has been variously explained by either the
      sixteenth-century introduction of birds into Iberia from the Far East, or by the
      loss of individuals from the central part of their range as a result of
      Pleistocene glaciations. We have used the mitochondrial control region to
      undertake a molecular phylogenetic analysis of the AWM, with sequences examined
      from individuals collected from across the current distribution range and
      incorporating representatives of all currently defined subspecies. The Western
      birds are genetically distinct from their Asian congeners and their divergence is
      basal in the phylogenetic tree. This indicates that the AWM is native to Iberia
      and not the result of a recent introduction from Asia. In Asia, two major
      mitochondrial DNA lineages were identified. These correspond to an Inland Asia
      group and a Pacific Seaboard group, and are separated topographically by the Da
      Hingan Ling mountains and the Yellow Sea. Molecular clock estimates suggest that
      these divergences are associated with Pleistocene glaciations. Furthermore, our
      data do not support the current classification of the AWM into 10 subspecies, as
      defined based on morphology and geographical distribution.

PMID- 12204128
TI  - Do pheromones reveal male immunocompetence?
AB  - Pheromones function not only as mate attractors, but they may also relay
      important information to prospective mates. It has been shown that vertebrates
      can distinguish, via olfactory mechanisms, major histocompatibility complex types
      in their prospective mates. However, whether pheromones can transmit information
      about immunocompetence is unknown. Here, we show that female mealworm beetles
      (Tenebrio molitor) prefer pheromones from males with better immunocompetence,
      indicated by a faster encapsulation rate against a novel antigen, and higher
      levels of phenoloxidase in haemolymph. Thus, the present study indicates that
      pheromones could transmit information about males' parasite resistance ability
      and may work as a reliable sexual ornament for female choice.

PMID- 12204129
TI  - Sex-specific foraging behaviour in a monomorphic seabird.
AB  - Sexual differences in the foraging behaviour of parents have been observed in a
      number of sexually sizedimorphic birds, particularly seabirds, and the usual
      inference has been that these sex-specific differences are mediated primarily by
      differences in body size. To test this explanation, we compared the foraging
      behaviour of parents in a monomorphic seabird species, the northern gannet Morus
      bassanus. Using specially designed instruments and radio telemetry we found that
      individuals of both sexes were consistent in the directions and durations of
      their foraging trips. However, there were significant differences in the foraging
      behaviour of males and females. Female gannets were not only more selective than
      males in the areas where they foraged, but they also made longer, deeper dives
      and spent more time on the sea surface than males. As the sexes are
      morphologically similar in this species, then these differences are unlikely to
      have been mediated by body size. Our work highlights the need to investigate
      sexual differences in the foraging behaviour of seabirds and other species more
      closely, in order to test alternative theories that do not rely on differences in
      body size.

PMID- 12204130
TI  - Colony-level impacts of parasitoid flies on fire ants.
AB  - The red imported fire ant is becoming a global ecological problem, having invaded
      the United States, Puerto Rico, New Zealand and, most recently, Australia. In its
      established areas, this pest is devastating natural biodiversity. Early attempts
      to halt fire ant expansion with pesticides actually enhanced its spread. Phorid
      fly parasitoids from South America have now been introduced into the United
      States as potential biological control agents of the red imported fire ant, but
      the impact of these flies on fire ant populations is currently unknown. In the
      laboratory, we show that an average phorid density of as little as one attacking
      fly per 200 foraging ants decreased colony protein consumption nearly twofold and
      significantly reduced numbers of large-sized workers 50 days later. The high
      impact of a single phorid occurred mainly because ants decreased foraging rates
      in the presence of the flies. Our experiments, the first (to our knowledge) to
      link indirect and direct effects of phorids on fire ants, demonstrate that
      colonies can be stressed with surprisingly low parasitoid densities. We interpret
      our findings with regard to the more complex fire ant-phorid interactions in the
      field.

PMID- 12204131
TI  - Heteropopulation males have a fertilization advantage during sperm competition in
      the yellow dung fly (Scathophaga stercoraria).
AB  - Sexual conflict occurs whenever there is not strict genetic monogamy. The
      sexually antagonistic coevolution that potentially occurs because of this
      conflict involves adaptation by one sex followed by the counter-adaptation by the
      other, and may be thought of as an evolutionary arms-race. As a result of these
      cycles of antagonistic coevolution, females from one population may be less
      resistant to heteropopulation males, at least after short periods of allopatry,
      as they will not have evolved any resistance to them. We tested this prediction
      in yellow dung fly (Scathophaga stercoraria) populations from the UK and
      Switzerland. Males from each population mated as first and second males to
      females from each population, and the mean numbers of offspring sired by the last
      male to mate in each situation were compared. We also compared the fertility and
      fecundity of single females mated to males from both populations, as well as the
      fertility and fecundity of the F(1) crosses. Both crosses produced viable and
      fertile offspring and the offspring sex ratios were not skewed. However, the
      fecundity of F(1)-cross females was greater than that of the parentals. In the
      sperm-competition experiment, there was a significant interaction between male
      and female origin influencing the proportion of offspring sired by the second
      male to mate, with heteropopulation males always outcompeting conpopulation
      males. This effect was independent of copula duration and the delay between
      copulations. In a separate experiment, we tested to see whether this was due to
      female preference for genetically dissimilar males but found no evidence for
      paternity biasing based on genetic similarity. Our results therefore seem to be
      best explained by sexually antagonistic coevolution as females appear less
      resistant to males with which they have not coevolved.

PMID- 12204132
TI  - Why offspring delay dispersal: experimental evidence for a role of parental
      tolerance.
AB  - Approximately 3% of all bird species live in families based on a prolonged parent
      offspring association. Formation of family groups often appears to be associated
      with various constraints on the possibilities of independent reproduction for the
      offspring. However, delayed dispersal is not the only alternative for offspring
      that defer reproduction. To account for the formation of a family group it is
      also necessary to explain why non-dispersing offspring forego the alternative
      options to join other groups as 'extra birds' or to become 'floaters' and roam
      between territories. We removed fathers from Siberian jay Perisoreus infaustus
      family groups to test the proposal that nepotistic parental tolerance gives the
      natal territory a special value for the offspring, which they cannot find
      elsewhere and that makes them stay. In this species, parents are more tolerant of
      their retained offspring than towards immigrant extra birds. In response to the
      removal of fathers, retained offspring dispersed, whereas there was no similar
      response among the unrelated extra birds. Retained offspring, however, left only
      after despotic immigrant alpha-males replaced removed fathers, indicating that
      the presence of fathers is an essential motive for offspring to delay their
      dispersal. By blocking immigrant and unrelated males from becoming alpha-males
      and by being tolerant themselves, fathers provide a 'safe haven' in the natal
      territory where retained offspring can avail themselves of available resources
      without any, or only mild, competitive interference.

PMID- 12204134
TI  - Extinction and the loss of functional diversity.
AB  - Although it is widely thought to influence ecosystem processes, there is little
      consensus on an appropriate measure of functional diversity. The two major
      perspectives, to date, are to assume that every species is functionally unique,
      or to assume that some species are functionally identical, such that functional
      groups exist. Using a continuous measure of functional diversity (FD) derived
      from the quantitative functional traits of species, we show that the loss of
      functional diversity from six natural assemblages was rapid compared with rates
      of loss from comparable simulated assemblages. Loss of FD occurred faster than
      loss of functional-group diversity in four of the six natural assemblages.
      Patterns of functional-group diversity loss depended on the number of functional
      groups and the number of species in an assemblage. Extinctions that occurred
      first for species with particular traits (e.g. low leaf nitrogen concentration,
      deep roots and large body size) caused greater loss of FD than expected by chance
      in four of the six natural assemblages. In two real assemblages, these trait
      dependent extinctions had more severe effects on FD than our simulated worst-case
      extinction scenario. These data suggest that conserving a large proportion of the
      functional traits of species requires conserving a large proportion of all
      species.

PMID- 12204133
TI  - Large-scale species-richness gradients in the Atlantic Ocean.
AB  - The increase in species richness from the poles to the Equator has been observed
      in numerous terrestrial and aquatic taxa. A number of different hypotheses have
      been put forward as explanations for this trend, e.g. area and energy
      availability. However, whether these hypotheses apply to large spatial scales in
      marine environments remains unclear. The present study shows a clear latitudinal
      gradient from high to low latitude (from 80 degrees N to 70 degrees S) in marine
      species richness for 6643 species (fishes and invertebrates) in 10 different taxa
      dwelling in benthic and pelagic habitats on both sides of the Atlantic. The
      patterns in benthic taxa are strongly influenced by coastal hydrographic
      processes, with marked peaks and troughs, and consequently the gradients are not
      symmetric along both Atlantic sides. Pelagic taxa show a plateau-shaped
      distribution and the influence from coastal events on gradients could not be
      demonstrated. The relationships between species richness and different
      environmental factors indicate that area size does not explain the latitudinal
      pattern in benthic species richness on a large spatial scale. Sea-surface
      temperature (positive relationship) is the best predictor of this pattern for
      benthic species, and nitrate concentration (negative relationship) is the best
      predictor for pelagic species. The results call into question the existence of a
      single primary cause that would explain the pattern in marine species richness on
      a large spatial scale.

PMID- 12204135
TI  - Carotenoid concentration in barn swallow eggs is influenced by laying order,
      maternal infection and paternal ornamentation.
AB  - Carotenoids are critical to embryonic development, immunity and protection from
      oxidative stress. Transmission of carotenoids to the eggs may affect development
      and maturation of immunity in offspring, but carotenoids may be available to
      females in limiting amounts. Females may thus transfer carotenoids to the eggs
      differentially in relation to the reproductive value of the offspring as affected
      by sexual ornamentation of their father. In this study of maternal allocation of
      carotenoids to the eggs in the barn swallow (Hirundo rustica), females whose
      immune system had been experimentally challenged with an antigen had smaller
      lutein concentrations in their eggs than controls. We manipulated the size of a
      secondary sexual character (tail length) of males, and analysed the effect of
      manipulation on allocation of lutein to eggs by their vaccinated mates. Contrary
      to our prediction based on parental allocation theory, mates of tail-shortened
      males had a larger lutein concentration in their eggs compared with those of
      control and tail-elongated males. According to previous studies, offspring of
      short-tailed males have larger exposure and/or susceptibility to parasites. A
      larger lutein concentration in the eggs of females mated to males with
      experimentally reduced ornaments may thus reflect adaptive maternal strategies to
      enhance offspring viability.

PMID- 12204136
TI  - Metabolic consequences of hard work.
AB  - When an animal has to meet increased demands on its working capacity, for
      example, for thermoregulation or parental care, two strategies are available. The
      animal can reallocate energy from costly maintenance processes - such as
      immunological defence or DNA repair systems (compensation hypothesis) - or it may
      try to increase the rate of energy intake or efficiency of digestion by
      increasing the size of the alimentary tract (increased-intake hypothesis). By
      manipulating brood size, I affected parental effort among marsh tits (Parus
      palustris) as demonstrated by a significant increase in parental feeding rate
      with experimental brood size. Basal metabolic rate (BMR) increased both with
      manipulated brood size and individual feeding rate, supporting the predictions
      from the increased-intake hypothesis. Furthermore, I found a direct positive
      relation between BMR and energy expenditure, measured with the help of the doubly
      labelled water technique. The cost of achieving a higher working capacity is
      substantial since BMR increases more quickly than the surplus energy available
      for work. Since the cost of a high sustained workload was not primarily dependent
      on a reallocation of energy away from maintenance, such a cost should be searched
      for among the detrimental effects of a high metabolic rate per se, for example,
      an increased oxidative damage to DNA, proteins and lipids.

PMID- 12204137
TI  - A brief history of the Ryan White CARE Act in the USA and its implications for
      other countries.

PMID- 12204138
TI  - Background for the studies on ancillary services and primary care use.
AB  - Timely and optimal HIV primary care is a key tenet of the Ryan White CARE Act, a
      safety net programme for vulnerable and marginalized people living with HIV in
      the USA. Health services researchers, local providers and policy makers suspect
      that ancillary services are necessary to improve entry into and retention in HIV
      primary care for vulnerable populations experiencing barriers to HIV services,
      including access to antiretroviral therapies. This paper provides background to
      the eight studies featured in this special supplement to AIDS Care. The eight
      studies examine retrospectively ancillary (support) services data collected after
      1996 in six HIV epicenters (New York and Chicago, plus four sites included in the
      Client Demonstration project-Los Angeles, San Francisco, Orange County
      [California] and Washington, DC), three smaller hard-hit cities (Boston, New
      Orleans and St Louis) and several states (California, plus Michigan and Virginia
      from the Client Demonstration Projects). These varied delivery settings serve
      racial and ethnic minority populations, men who have sex with men, injection drug
      users, women and mothers. The studies use a range of analytic approaches to
      understand whether receipt of certain enabling services correlated with early
      entry into and retention in care. Ancillary services (support services such as
      case management, housing, food, transportation, mental health and substance abuse
      treatment) are used by local HIV medical and community-based organizations in
      facilitative strategies directed to populations that have difficulty entering or
      staying in HIV primary care. Understanding the contribution of ancillary services
      to timely entry into and consistent use of primary care, including the expanding
      range of HIV therapeutics, is important to service delivery system planners and
      resource allocation decision-makers.

PMID- 12204139
TI  - The impact of ancillary HIV services on engagement in medical care in New York
      City.
AB  - The advent of antiretroviral therapies in 1996 prompted an interest in the role
      played by ancillary services in improving access to and retention in medical
      care, particularly since the success of the new therapies is often contingent
      upon ongoing and appropriate primary medical care. Using self-reported survey
      data from a longitudinal representative sample of 577 HIV-positive adults in New
      York City, this paper explores the impact of such supportive services as drug
      treatment, case management, housing assistance, mental health treatment and
      transportation on engagement with medical care. The study's principal finding was
      that specific ancillary services were significantly associated with an increase
      in an individual's likelihood of entering medical care and maintaining
      appropriate medical care services for HIV, particularly when the services
      addressed a corresponding need.

PMID- 12204140
TI  - HIV multidisciplinary teams work: support services improve access to and
      retention in HIV primary care.
AB  - The multidisciplinary team model of HIV care evolved out of necessity due to the
      diverse characteristics and needs of people living with HIV disease. Though it is
      now accepted as the international standard of care, it represents a significant
      departure from methods of care for other infectious diseases, and debate
      continues regarding the effectiveness of its interventions. The debate has been
      largely uninformed by data; for example, little is known about the relationship
      between ancillary support services and primary care outcomes. We hypothesized
      that support services increase access to and retention in HIV primary care in an
      inner city public hospital clinic. We conducted a retrospective analysis of
      clinical data sets on 2,647 patients at the CORE Center, Chicago from 1997-1998
      to investigate the relationship between four support services-case management
      (CM), transportation (TRANS), mental health (MH) and chemical dependency (CD)-and
      access to and retention in HIV primary care. We found that patients who received
      each of these services were significantly more likely to receive any care,
      regular care and had more visits than patients with no service, and retention
      increased by 15-18%. Female gender, younger age, self-pay status and IDU
      predicted less regular care. Need for all services was substantial and
      significantly greater in women. Outcomes improved to the greatest extent among
      patients who needed and received each service. We conclude that support services
      significantly increased access to and retention in HIV primary care. Our findings
      validate the multidisciplinary team model of HIV care, and suggest that health
      services that are tailored to the express needs of patients lead to better care
      and improved health outcomes. Further testing of changes in health care delivery
      to meet the rapidly changing needs of people living with HIV disease and respond
      to the constantly changing practice of HIV medicine is urgently needed to
      maintain and extend the advances in HIV care outcomes of the past decade.

PMID- 12204141
TI  - Association of ancillary services with primary care utilization and retention for
      patients with HIV/AIDS.
AB  - Fenway Community Health Center (FCHC), located in Boston, Massachusetts, provides
      comprehensive care to persons with HIV/AIDS, including medical, mental health and
      other health-related services. In this paper, we present results from an analysis
      of existing data about the demographic and clinical characteristics, service
      needs and utilization patterns, and primary care retention of HIV-positive
      primary care patients seen at FCHC during a 24-month study period. Patient data
      were extracted from Logician, FCHC's electronic medical record system, and
      imported into Microsoft Access, Microsoft Excel and SAS for manipulation and
      analysis. A total of 999 unique individuals were included in the study
      population. Most were men (97%), white (75%) and between 39 and 80 years of age.
      Patients averaged 6.7 medical visits annually at FCHC, and 61% had at least one
      medical visit every six months. Significant predictors of primary care
      utilization were insurance status, HIV disease stage, being on combination
      therapy, first CD4 count, first viral load level and receipt of ancillary
      services. Need and receipt of ancillary services were found through medical and
      case management record review; case management was the most used ancillary
      service, received by 36% of the study population. For most ancillary services,
      clients with assessed need had documented receipt of the service. Publicly
      insured and/or Ryan White CARE Act-funded patients had the greatest ancillary
      service utilization. The influence of ancillary services upon primary care entry
      could not be evaluated with available data; however, their influence upon primary
      care was significant. For patients who received primary care in every continuous
      six-month period, statistically significant associations were found with receipt
      of mental health care, case management, drug assistance, food/nutrition,
      complementary services and housing. Using the more rigorous FCHC standard of care
      (minimum of four primary care visits per year), significant associations were
      also found with transportation, legal services and substance abuse treatment. For
      non-whites and women, mental health care, food/nutrition, housing and
      transportation had particular significance.

PMID- 12204142
TI  - The impact of ancillary services on primary care use and outcomes for HIV/AIDS
      patients with public insurance coverage.
AB  - To better understand the impact of ancillary services on access to primary care,
      utilization of health services, costs and health status of HIV/AIDS patients, we
      studied adult HIV/AIDS patients eligible for public insurance for low-income
      people (Medicaid) in eastern North Carolina. Using primary data from a 1997
      survey of such patients linked to Medicaid claims, multivariate logit analysis
      was used to estimate the effect of receiving housing, legal services and
      substance abuse treatment and of self-reported failure to obtain transportation
      and child care services on: (a) adequacy and use of primary care; (b) CD-4
      counts; (c) viral load; and (d) self-rated health status. Between two-thirds and
      four-fifths of patients needing ancillary services obtain them. Receipt of
      housing and legal services were found to have a positive relationship with access
      to primary care. Difficulties in obtaining transportation and receipt of
      substance abuse services had a negative relationship with receipt of adequate
      primary care. On balance, these findings provide some support for continued
      public funding for various ancillary services to improve patient access to needed
      primary care. At current funding levels, not all patients needing help appear
      able to obtain such services.

PMID- 12204143
TI  - Recipients in need of ancillary services and their receipt of HIV medical care in
      California.
AB  - For many individuals with access to quality medical care, HIV disease is no
      longer a critical short term illness but a chronic condition giving rise to more
      clients requiring ongoing medical care. Programs funded by the federal Ryan White
      Comprehensive AIDS Resources Emergency Act not only provide essential medical
      care for these individuals but also facilitate access to medical care services.
      These programmes fund services, including case management, transportation, and
      translation assistance, that feature ongoing assistance and enable individuals to
      remain in the health care system. Because of the importance of maintaining the
      strict drug regimen, retention in care is also an important part of the overall
      HIV care component. This study analyzed the relationship of ancillary services
      and a federal health programme client's receipt of medical care and retention in
      the health care system. We defined a cohort in need of ancillary services in part
      by a questionnaire designed to identify factors relating to need. These factors
      included education, language, and substance use. By merging client level data
      files we were able to identify medical service utilization trends among the
      individuals in the cohort who received a high number of ancillary services (more
      than 11 ancillary service visits in the two-year study period, n = 138) and those
      who received few services (fewer than six ancillary service visits in the two
      year study period, n = 132). Results suggest that the receipt of ancillary
      services is associated with receipt of and retention in primary medical care. We
      found that for federal health programme clients in need of ancillary services, a
      positive relationship existed between their receipt of ancillary services and
      their access to primary medical care (p </= 0.001). This observation held
      constant when age, race, gender, and insurance coverage were controlled for.
      Also, these clients were more likely to be seen by a medical doctor at least once
      in three consecutive six-month periods when they received needed ancillary
      services (p </= 0.01).

PMID- 12204144
TI  - Women with HIV infection: a model of university-based care, training and
      research.
AB  - The growth of human immunodeficiency virus type-1 (HIV) infection among women in
      the USA has been coincident with an international momentum to better address the
      specific health care needs of women. This paper provides an overview of a
      demonstration model for comprehensive HIV care of adolescent and adult women in
      an academic setting. The paper contains a descriptive summary of a university
      based demonstration model of comprehensive care for women with HIV infection.
      During 1997-1998, there were 279 urban and rural Midwest adolescent and adult
      women with HIV infection in care at this model programme. Medical care
      encompassed subspecialty HIV care, obstetrical and gynaecological care, primary
      care of non-HIV comorbidities, mental health assessments and family planning in a
      safe, university-based environment. For 279 women during the two-year period,
      health services included the detection and treatment of sexually transmitted
      diseases (56%) and cervical dysplasia (35%), perinatal care (12%) and screening
      and referral for substance abuse treatment (30%). There was no mother-to-child
      HIV transmission among 33 pregnant women enrolled in the Center prior to
      delivery, and transmission by three of nine women enrolled after delivery. Only
      167 (60%) women were compliant with biannual medical visits during 1997-1998.
      Integral to the health services delivery was the provision of ancillary support
      services intended to enhance optimal medical care for this cohort of women. This
      university-based model of care also incorporated HIV provider training and
      formative HIV research. Structured medical and public health experiential
      learning opportunities occurred for medical and social work students, medicine
      residents, infectious diseases fellows, nurses and other professional health care
      workers. Clinical investigations of adolescent and adult women have complemented
      care and training, with funded research in HIV medication adherence and health
      services research. In follow-up, 71% of these women remained active in care in
      1999. Retention of vulnerable populations in care may be a big challenge over the
      next decade, despite the availability of potent antiretroviral therapies.

PMID- 12204145
TI  - Associations between HIV-positive individuals' receipt of ancillary services and
      medical care receipt and retention.
AB  - This study examines associations between HIV-positive individuals' receipt of
      ancillary services and their receipt of and retention in primary medical care.
      Ancillary care services examined include case management, mental health and
      substance abuse treatment/counseling, advocacy, respite and buddy/companion
      services, as well as food, housing, emergency financial assistance, and
      transportation. The selection criterion used was the receipt of care from January
      June 1997 at selected facilities receiving funding under the Ryan White
      Comprehensive AIDS Resources Emergency (CARE) Act, a federally funded safety net
      programme in the USA. The receipt of each ancillary service was associated with
      the receipt of any primary medical care from a safety net provider. All ancillary
      services were more strongly associated with primary care receipt than with
      retention in care or the mean number of primary care visits per year. Mental
      health and substance abuse treatment/counselling, client advocacy, respite care
      and buddy/companion services all had significant associations with all primary
      medical care measures. This is the first time in one study that the primary
      medical and ancillary services received by all clients at safety net-funded
      providers from multiple cities and states have been examined. All types of safety
      net providers, from the largest medical centre to the smallest community-based
      organization, are represented in this study. The patterns seen here are similar
      to the findings from the other, geographically more restricted, studies reported
      on in this volume.

PMID- 12204146
TI  - The role of ancillary services in client-centred systems of care.
AB  - The studies in this issue reflect the operation of the Ryan White CARE Act's
      holistic model of health and support services for people living with HIV in the
      USA. Ancillary services available through the CARE Act are responsive to
      predisposing factors, enabling factors, and system characteristics that pose
      barriers to clients' receipt of primary medical care. That nearly all of the
      studies use cross-sectional rather than longitudinal data makes it difficult to
      draw causal inferences. Taken as a whole, however, the studies suggest that
      receipt of ancillary services such as case management, mental health and
      substance abuse treatment, transportation, and housing assistance is associated
      with primary care entry and retention among CARE Act clients. The studies and the
      literature out of which they arise suggest that there is a need to refine further
      our understanding of care systems so that we can refine the care systems
      themselves. Among the concepts proposed for the study of care systems are
      comprehensiveness, capacity, coordination, integration, cultural competence, and
      client-centredness.

PMID- 12204147
TI  - A health services research perspective on the use of ancillary services to retain
      persons living with HIV/AIDS in primary care.

PMID- 12204148
TI  - Drug use, travel and HIV risk.
AB  - A study was conducted to examine the travel experiences of a community sample of
      160 drug users and 44 non-users recruited as part of a study of HIV risk. Of the
      sample, 47% (96/204) reported intercity travel in the previous ten years. Results
      showed that men were more likely to travel than women, Anglos more than
      minorities, and young persons more than old. When travellers testing HIV
      seropositive (n = 13) were compared with seronegative travellers, HIV-positive
      travellers reported more sex while travelling than HIV-negative persons, but
      virtually all of the difference reported involved sex with condoms. There were no
      significant differences in sex risk behaviours while travelling between drug
      users and non-drug users, or in sex risk behaviors between drug injectors and non
      injectors. Travellers had fewer injection partners while travelling than they had
      while at home. There was also a significant difference in number of sex partners
      with whom a condom was not used, with fewer sex partners while travelling.

PMID- 12204149
TI  - Sexual behaviour patterns and condom use in Tanzania: results from the 1996
      Demographic and Health Survey.
AB  - We conducted this study to determine the factors associated with high-risk sexual
      behaviour and condom use among men and women who participated in the 1996
      Tanzania Demographic and Health Survey (TDHS); and to assess changes in sexual
      behaviour between 1991/92 and 1996 TDHS. Respondents were regarded to have
      practised high-risk sexual behaviour if they were married or cohabiting and had
      other regular or non-regular sexual partners; or if they were unmarried and had
      non-regular partners or multiple regular partners. About 8% of women and 29% of
      men practised high-risk sexual behaviour. High-risk sexual behaviour was common
      among younger men and women, and decreased with increasing level of education in
      women. Respondents who were unmarried, Muslims and those who perceived themselves
      at increased risk of HIV/AIDS were more likely to practise high-risk sexual
      behaviour. About 4% of women and 15% of men reported to have used condoms during
      their last sexual encounter. Condom users were significantly more likely to
      practise high-risk sexual behaviour. Overall, no major changes in sexual
      behaviour and condom use were observed during the period between the two surveys.
      Predictors of high-risk sexual behaviour and condom use identified in this report
      provide valuable information that can be used to design targeted HIV/AIDS
      interventions in Tanzania.

PMID- 12204150
TI  - In a minority of gay men, sexual risk practice indicates strategic positioning
      for perceived risk reduction rather than unbridled sex.
AB  - The aim of this analysis was to examine gay men's sexual risk practice to
      determine patterns of risk management. Ten cross-sectional surveys of gay men
      were conducted six-monthly from February 1996 to August 2000 at Sydney gay
      community social, sex-on-premises and sexual health sites (average n = 827).
      Every February during this period, five identical surveys were conducted at the
      annual Gay and Lesbian Mardi Gras Fair Day (average n = 1178). Among the minority
      of men who had unprotected anal intercourse which involved ejaculation inside
      with a serodiscordant regular partner, there was a clear pattern of sexual
      positioning. Few regular couples were both receptive and insertive. Most HIV
      positive men were receptive and most HIV-negative men were insertive. Among the
      minority of men who had unprotected anal intercourse which involved ejaculation
      inside with casual partners, there was also a pattern of sexual positioning.
      Whereas many casual couples were both receptive and insertive (especially those
      involving HIV-positive respondents), among the remainder HIV-positive men tended
      to be receptive and HIV-negative men tended to be insertive. These patterns of
      HIV-positive/receptive and HIV-negative/insertive suggest strategic risk
      reduction positionings rather than mere sexual preferences among a minority of
      gay men. If so, they point not to complacency but to an ever more complex domain
      of HIV prevention.

PMID- 12204151
TI  - HIV-related behaviours among voluntary blood donors in Hong Kong.
AB  - The present study examined the prevalence of and factors associated with
      deferrable risk behaviours practised by male voluntary blood donors in Hong Kong.
      Attitudes and knowledge related to HIV/AIDS and blood donation among both male
      and female blood donors were also studied. In total, 2,162 (1,190 male and 972
      female) blood donors in four Hong Kong Red Cross Blood Transfusion Services
      (HKRCBTS) centres completed an anonymous structured questionnaire. About 11% of
      the male respondents have practised deferrable risk behaviours (e.g. sharing
      syringes, commercial sex-networking, or having sex with another man).
      Furthermore, among male respondents, 5.9% indicated that they are using blood
      donations as a means of testing for their HIV status. These male 'potential test
      seekers' tended to be younger, single, unemployed and first-time donors; relevant
      knowledge and perceptions towards the screening guideline were also associated
      with potential test seeking and deferrable risk. About 5% of all respondents
      would go to the HKRCBTS to perform an HIV test, if required. Many blood donors in
      Hong Kong were not knowledgeable about HIV-related issues. There is a need to
      review the effectiveness of the present deferral system, which is based on the
      goodwill of the donor to disclose personal health risk factors.

PMID- 12204152
TI  - Consistent condom use among drug-using youth in a high HIV-risk neighbourhood.
AB  - The objectives of this study were to determine predictors of consistent condom
      use in heterosexual relationships of young adults who use hard drugs in a
      neighbourhood with widespread drug-use-connected HIV. We interviewed 196 18-24
      year olds who injected drugs or used heroin, cocaine or crack in the prior year
      and lived in the Bushwick neighbourhood of New York City. Interviews covered
      sociodemographics, substance use and sexual networks. The unit of analysis is the
      relationship; the dependent variable measures consistent condom use over the
      prior 30 days in a given relationship. Consistent condom use was reported in 26%
      of 377 non-commercial relationships and in all of 22 commercial relationships.
      Using multiple logistic regression, consistent condom use in non-commercial
      relationships was more likely in relationships that are not 'very close'; for men
      (but not women) with peers whose norms are more favourable to condom use; and for
      subjects who had concurrent sex partners in the last 12 months. In conclusion, we
      found that: (1) the lack of relationship between the peer norms of drug-using
      women and their condom use suggests they may have little control over condom use
      in their relationships-programmes should attempt to empower young women drug
      users and to develop ways for their peers to influence the men in their lives;
      (2) epidemiologically, the positive association of concurrency to consistent
      condom use suggests that condom use may be restricting HIV spread through the
      community-the presence of consistent condom use in all of the commercial sexual
      relationships also may restrict HIV spread; (3) prevention efforts should attempt
      to change peer cultures as a way to develop self-sustaining risk reduction. These
      changes should include changes in gender roles and power relations.

PMID- 12204153
TI  - Women migrant workers' vulnerability to HIV infection in Hong Kong.
AB  - Research on population mobility and HIV/AIDS risk among migrant populations is
      quite limited, and research on migrant women workers' vulnerability is further
      limited. Hong Kong, the Special Administrative Region of China, has currently
      about 200,000 women migrant workers working as domestic helps. This paper reports
      migrant women worker's access to AIDS-related health information and health care
      facilities, perceptions about vulnerability, and risk behaviour profile. Data was
      collected through a pre-tested questionnaire from a random sample of 2,010 women
      migrant workers. A majority of the migrant women workers (63.6%) have been living
      and working in Hong Kong for between 4-10 years. Fifty-four per cent of the
      respondents felt that being a female they were vulnerable to HIV infection.
      Overall, the knowledge regarding HIV/AIDS and its route of transmission is
      inadequate amongst the migrant women workers in Hong Kong. It appears that AIDS
      related information education and communication needs of women migrants workers
      are not met by the current HIV prevention and care activities in Hong Kong. The
      study indicates that migrant women workers who experienced sexual violence (9%)
      in Hong Kong perceive themselves to be 'at risk' of HIV infection. Seventy per
      cent of the respondents reported that they have felt discriminated against in
      Hong Kong, of which 42% felt discriminated against in Hong Kong hospitals.
      Addressing discrimination in health care settings is an essential element of AIDS
      prevention. The discussion urges researchers and policy makers to pay more
      attention to the vulnerability of migrant women workers.

PMID- 12204154
TI  - Closing the digital divide in HIV/AIDS care: development of a theory-based
      intervention to increase Internet access.
AB  - Advances in information technology are revolutionizing medical patient education
      and the Internet is becoming a major source of information for people with
      chronic medical conditions, including HIV/AIDS. However, many AIDS patients do
      not have equal access to the Internet and are therefore at an information
      disadvantage, particularly minorities, persons of low-income levels and
      individuals with limited education. This paper describes the development and
      pilot testing of a workshop-style intervention designed to close the digital
      divide in AIDS care. Grounded in the Information-Motivation-Behavioral Skills
      (IMB) model of health behaviour change, we developed an intervention for persons
      with no prior history of using the Internet. The intervention included
      instruction in using hardware and search engines, motivational enhancement to
      increase interest and perceived relevance of the Internet, and skills for
      critically evaluating and using health information accessed via the Internet.
      Participants were also introduced to communication and support functions of the
      Internet including e-mail, newsgroups and chat groups. Pilot testing demonstrated
      feasibility, acceptability and promise for closing the digital divide in HIV/AIDS
      care using a relatively brief and intensive theory-based intervention that could
      be implemented in community settings.

PMID- 12204155
TI  - Chatters on the Internet: a special target group for HIV prevention.
AB  - This study examined characteristics of men who use gay chat boxes on the
      Internet, including dating behaviour and sexual risk-taking with sex partners who
      were initially met through chatting. Men on chat boxes were asked to complete a
      brief questionnaire on the Internet. The questionnaire contained questions on
      demographics, chatting-related variables, and dating and risk-taking sexual
      behaviour. The results show that a large majority of the 190 respondents reported
      actual encounters as well as sex with men who were initially met through
      chatting. Almost 30% of the respondents who engaged in sex with chat dates
      reported inconsistent safe sexual behaviour. The level of unprotected sex
      increased as the number of sex partners who were met through chatting increased.
      These results suggest that chatters on the Internet may be a new target group for
      HIV prevention. Further study is needed to gain insight into the feasibility of
      prevention efforts for this target group.

PMID- 12204156
TI  - HIV/AIDS and care provider attributions: who's to blame?
AB  - The discovery of HIV/AIDS prompted a profusion of research focusing on the
      disease and its causes. Though the bulk of this research emphasizes behavioural
      risk factors, treatment and disease progression, researcher efforts are beginning
      to examine the public's attitude toward individuals who are HIV-positive or have
      developed AIDS. Utilizing Weiner's Attribution Theory, the current study examines
      the beliefs of social service providers who work directly with individuals
      affected by HIV/AIDS. Forty-six (28 female and 18 male) HIV/AIDS social service
      providers from three community-based organizations were asked to read a
      hypothetical scenario depicting an individual at-risk for HIV/AIDS because of
      multiple high-risk behaviours. The gender of the target was manipulated and at
      the conclusion of the scenario participants completed a questionnaire designed to
      assess attributions. Results of the study show that social service providers who
      perceive individuals as more responsible for their illness report increased
      anger, attribute more blame and express less willingness to help those at-risk
      for HIV/AIDS. This research suggests that despite growing numbers of media
      campaigns and national distribution of information regarding the disease and its
      transmission, in general, people continue to stigmatize and place blame on those
      at-risk.

PMID- 12204157
TI  - Pattern of responses to HIV transmission questions: rethinking HIV knowledge and
      its relevance to AIDS prejudice.
AB  - This paper intends to investigate the connection between HIV transmission
      knowledge and prejudicial attitudes towards people with HIV/AIDS (PWAs), with an
      emphasis on exploring the pattern of cognitive profile in response to knowledge
      questions. Data for the present study were derived from the 'Health Attitudes and
      Health Seeking Behavior Study', a telephone survey of a nationally representative
      sample, aged 20 to 70, from April to May 1997 in Taiwan. A total of 2,471
      respondents who had heard of AIDS and knew that it was infectious were included
      in the analysis. Based on answers to four transmission-route items (blood
      transfusion, mother-foetus, sexual contacts, needle sharing) and two casual
      contact items (shaking hands and sharing utensil), a variable 'pattern of
      knowledge performance' was constructed, by which the respondents were clustered
      into five knowledge groups. Bivariate and multivariate analyses illustrated the
      greater explanatory power of pattern of knowledge performance rather than
      additive scoring of knowledge items to PWAs' prejudice. Moreover, it was the
      responses to casual-contact rather than transmission-route questions that made a
      greater contribution to PWAs' prejudice. Special attention is given to the
      possible perceptual undertaking inherent in the five types of knowledge group. To
      implement effective AIDS prevention campaigns and interventions, the design for
      increasing the risk perception of the correct HIV transmission routes should
      differ from that of reducing the risk perception of the casually transmitted
      routes.

PMID- 12204158
TI  - The paradox of public HIV disclosure.
AB  - In order to examine the impact on HIV-positive people of publicly disclosing
      their status, in-depth interviews were conducted with 75 HIV-positive speakers
      from 20 countries in Africa and the Asia-Pacific region. Decreasing stigma and
      stopping new infections were equally strong motivators in becoming community AIDS
      educators. Although few respondents were trained, most had good support from
      peers and/or family. Public disclosure led to a diminution of discrimination.
      Speaking out was extremely rewarding. Disclosure led to a less stressful, more
      productive life and to improved wellbeing. Virtually all speakers from every
      setting had no regrets and saw only the benefits of public disclosure. The
      paradox of coming out openly as an HIV-positive person is that by facing AIDS
      related stigma, one finds psychological release-liberation from the burden of
      secrecy and shame. Disclosure is beneficial to all concerned. It enriches the
      speakers' lives and it helps the community. HIV-positive speakers may be a
      fundamental component of successful AIDS education campaigns, but increasing the
      numbers of people who are 'out' is only possible in a conducive environment.
      Governments and AIDS organizations must provide adequate emotional and optimal
      organizational support to those who do so, including peer support, counselling
      and appropriate training.

PMID- 12204161
TI  - The analyst at work: two sessions with Alba.
AB  - In this paper, the author presents clinical material that relates to two sessions
      with a patient called Alba. This analytic work, being of a somewhat unusual
      character, lends itself to discussion, the author feels, since the technical
      choices made are undoubtedly very personal and he believes many colleagues might
      have done things differently. The author endeavours to enrich the account of the
      sessions with his concomitant thoughts, so as to supply colleagues with the
      elements, atmosphere and developments of his internal workshop.

PMID- 12204159
TI  - Brazilian dental students' knowledge and attitudes towards HIV infection.
AB  - The purpose of this study was to investigate a group of Brazilian dental
      students' knowledge about HIV infection, the infection control measures utilized
      by the dental students, and students' attitudes towards treating HIV/AIDS
      patients. The study population consisted of 250 dental students from Universidade
      Federal da Bahia, Brazil, who were treating patients in clinics of the university
      and extra-mural rotations at the time of the study. The survey instrument was a
      self-administered questionnaire which consisted of 32 pre-coded questions and two
      open-ended questions. The overall response rate to the questionnaire was 54%.
      More than 80% of respondents (N = 135) considered every dental patient a
      potential HIV carrier. A majority of the students were aware of the association
      between HIV and Kaposi's sarcoma (92.5%), oral candidiasis (90.3%) and oral hairy
      leukoplakia (52.7%). A gender difference was observed in students' knowledge of
      oral manifestations and infection control measures, with females having better
      knowledge than males (p < 0.05). Because of certain inadequacies in knowledge and
      infection control practices among respondents, a curriculum focusing on the
      management of HIV/AIDS, including infection control and legal issues is
      recommended.

PMID- 12204163
TI  - A new reading of the origins of object-relations theory.
AB  - The author presents a reading of Freud's "Mourning and melancholia" in which he
      examines not only the ideas Freud was introducing, but, as important, the way he
      was thinking/writing in this watershed paper. The author demonstrates how Freud
      made use of his exploration of the unconscious work of mourning and of
      melancholia to propose and explore some of the major tenets of a revised model of
      the mind (which later would be termed "object-relations theory"). The principal
      tenets of the revised model presented in this 1917 paper include: (1) the idea
      that the unconscious is organised to a significant degree around stable internal
      object relations between paired split-off parts of the ego; (2) the notion that
      psychic pain may be defended against by means of the replacement of an external
      object relationship by an unconscious, fantasied internal object relationship;
      (3) the idea that pathological bonds of love mixed with hate are among the
      strongest ties that bind internal objects to one another in a state of mutual
      captivity; (4) the notion that the psychopathology of internal object relations
      often involves the use of omnipotent thinking to a degree that cuts off the
      dialogue between the unconscious internal object world and the world of actual
      experience with real external objects; and (5) the idea that ambivalence in
      relations between unconscious internal objects involves not only the conflict of
      love and hate, but also the conflict between the wish to continue to be alive in
      one's object relationships and the wish to be at one with one's dead internal
      objects.

PMID- 12204164
TI  - Termination of a fe/male transsexual patient's analysis: an example of general
      validity.
AB  - The author describes the termination of an analysis, which, while relating to the
      particular case of a male-to-female transsexual patient, may be relevant to all
      analysts, particularly those whose patients need to integrate disavowed and split
      off parts of themselves. The patient had undergone sex-change surgery at the age
      of 20. Having lived as a woman thereafter, she had asked for analysis some twenty
      years later. The author, who discussed the first three years of that analysis in
      an earlier paper, as well as her hesitation about undertaking it, considers that
      its termination after seven years illustrates not only the specific problems
      posed by transsexuals but also the general ones presented by "heterogeneous
      patients". To the best of her knowledge, this is the first published case history
      of a transsexual patient who has undergone surgery. In the author's view, the
      patient has acquired a new sense of internal unity based on a notion of sex
      differentiation in which mutual respect between the sexes has replaced confusion
      and mutual hate, and her quality of life has improved. On the general level, this
      termination shows how the reduction of paranoid-schizoid anxieties and the
      reintegration of split-off parts of the personality lead, as the depressive
      position is worked through, to a better toleration of internal contradictions, a
      new sense of cohesion of the self and a diminution of the fear of madness.

PMID- 12204165
TI  - From knowledge to competence: reflections on theoretical work.
AB  - In this paper, the author maintains that the language of the clinical situation
      is and should be that of common-sense psychology. The author argues that the
      languages of clinical theory and metapsychology are at a distinctive distance
      from clinical language. In fact, no theory could be produced, should this
      distance not be upheld. The function of clinical theory is to act as a corrective
      to the tendency of common-sense psychology to fall back into the banalities and
      prejudices of general ideology. In addition, the function of metapsychology is
      said to be that of scrutinising clinical theory and defining its range of
      operation. Due to the claimed distance between the common-sensical language of
      the clinical situation and the language of theory, the analyst must utilise
      specific "techniques" to appropriate the theoretical material and make it part of
      his competence and capacity for psychoanalytic action. This aspect of theoretical
      work is given the name "assimilation" and, in turn, relies upon a process where
      theoretical concepts are "deconstructed" as to their knowledge content.

PMID- 12204166
TI  - The triadic intersubjective matrix in supervision: the use of disclosure to work
      through painful affects.
AB  - The use of the psychoanalyst's subjective reactions as a tool to better
      understand his/her patient has been a central feature of clinical thinking in
      recent decades. While there has been much discussion and debate about the
      analyst's use of countertransference in individual psychoanalysis, including
      possible disclosure of his/her feelings to the patient, the literature on
      supervision has been slower to consider such matters. The attention to parallel
      processes in supervision has been helpful in appreciating the impact of affects
      arising in either the analyst/patient or the supervisor/analyst dyads upon the
      analytic treatment and its supervision. This contribution addresses the ways in
      which overlapping aspects of the personalities of the supervisor, analyst and
      patient may intersect and create resistances in the treatment. That three-way
      intersection, described here as the triadic intersubjective matrix, is considered
      inevitable in all supervised treatments. A clinical example from the termination
      phase of a supervised analysis of an adolescent is offered to illustrate these
      points. Finally, the question of self-disclosure as an aspect of the supervisory
      alliance is also discussed.

PMID- 12204167
TI  - Considerations on depressive conflict and its different levels of intensity:
      implications for technique.
AB  - This article considers the problem of depressive conflict (DC) and the
      difficulties that arise in integrating aggression towards the object of libidinal
      cathexis. This conflict results, in particular, from the destructive omnipotence
      that infantile fantasies attribute to the aggression. In order to better clarify
      Klein's very broad concept of the depressive position, three levels of severity
      of depressive conflict are proposed, depending on the type of fantasies
      concerning the loss of the object that predominate in the individual. These are:
      fantasies of catastrophic and irreparable destruction of the object
      ("parapsychotic" DC); fantasies of death and serious damage of the object ("para
      depressive" DC); and fantasies of rejection and loss of the love of the object
      ("para-neurotic" DC). Having looked at these theoretical hypotheses, their
      implications for technique will then be considered, particularly the importance
      of focusing the interpretation on guilt feelings rather than on drives in the
      transferential relationship. A clinical example drawn from the work of Klein and
      a clinical vignette of a particularly difficult analysis illustrate this
      technical hypothesis.

PMID- 12204168
TI  - Body, mother, mind: anorexia, femininity and the intrusive object.
AB  - This paper takes as its starting point the preponderance of female to male
      patients who suffer from anorexia. The author suggests that there may be
      something specific about certain experiences of femaleness which predispose
      towards anxieties of intrusion. Two contemporary theories of the aetiology of
      anorexia are outlined. Both of these suggest that the problem has its origins in
      intrusion or invasion of different sorts. The author suggests that many women who
      suffer from anorexia have an intrusive object instated in their minds, which may
      not necessarily be the result of actual intrusions in external reality. In the
      final part of the paper, the author examines the intrusiveness of anorexic
      patients in the transference and suggests that such patients very often harbour
      profound phantasies of intruding between the parents, with a wish to regain their
      special place with mother, untroubled by the presence of father. It is further
      suggested that the psychopathology underlying certain cases of anorexia leads to
      a failure in symbolisation. This failure in turn complicates the clinical
      picture, making such patients particularly difficult to think with about their
      difficulties.

PMID- 12204169
TI  - The need for true controversies in psychoanalysis: the debates on Melanie Klein
      and Jacques Lacan in the Rio de la Plata.
AB  - Controversies are part of the process of scientific knowing. In psychoanalysis,
      the diversity of theoretical, technical and epistemological positions makes the
      debate particularly necessary and by the same token difficult. In this paper, the
      author examines the function of controversies and the obstacles to their
      development, taking as examples the debates held in the Rio de la Plata (Buenos
      Aires and Montevideo) during the nineteen seventies, when the dominant Kleinian
      ideas came into contact with Lacanian thought. The author examines different
      examples of argumentative discourses, using concepts taken from the theory of
      argumentation. The major difficulties encountered did not hinge on
      characteristics pertaining to psychoanalytic theories (i.e. the lack of
      commensurability between them), but on the defensive strategies aimed at keeping
      each theory's premises safe from the opposing party's arguments. A true debate
      implies the construction of a shared argumentative field that makes it possible
      to lay out the different positions and see some interaction between them and is
      guided by the search for the best argument. When this occurs, controversies
      promote the discipline's development, even when they fail to reach any consensus.

PMID- 12204170
TI  - Max Eitingon and the struggle to establish an international standard for
      psychoanalytic training (1925-1929).
AB  - This paper deals with the first years of the IPA's International Training
      Commission (ITC). The author begins by outlining the Berlin model of training,
      including some less familiar aspects, and he describes how the foundation of the
      ITC in 1925 was designed for promoting the general establishment of
      institutionalised training according to this pioneer model. In relation to lay
      analysis, he highlights the issue of central power versus local autonomy with
      regard to admission policy. The latter part of the narrative is devoted to an ITC
      subcommittee ("Eitingon Committee"), appointed in 1927, which tried to formulate
      training guidelines for the whole IPA, again with a clear Berlin profile. The
      discussion of the draft of these guidelines among all branch societies (with
      Freud himself participating) revealed some interesting disagreements, while the
      "closed" nature of the system, as opposed to what later came to be called an
      "open system", was hardly challenged. The initiative failed, apparently through
      American opposition, but essentially because of the developmental gap between
      local societies as to the institution of specialised psychoanalytic training. The
      paper is based largely on unpublished material and also provides some information
      about Max Eitingon, the least well known of the early leaders of psychoanalysis.

PMID- 12204171
TI  - The rape of Medusa in the temple of Athena: aspects of triangulation in the girl.
AB  - The relationship between the Greek goddess Athena and her father Zeus, together
      with the competitive hostility she displays towards other females, is presented
      as illustrating some previously neglected aspects of triangular developmental
      conflicts in the little girl. Literature on "the Oedipus complex in the female"
      is reviewed and discussed. The mythological early histories of both Athena and
      the female monster Medusa are examined for the light they can shed on female
      developmental vicissitudes and resultant conflicts in both women and men.
      Unconscious split representations of women as assertive, phallic and dangerous,
      or alternatively passive, castrated and receptive result in defensive repudiation
      of the idea that a woman can be both actively assertive and also feminine and
      sexual. Athena's enraged action of transforming the beautiful young maiden Medusa
      into a monster as punishment for the "crime" of having been raped in her temple
      is discussed as illustrating an outcome of the lack of resolution of the little
      girl's early triangular conflicts.

PMID- 12204172
TI  - Bion's perspectives on psychoanalytic method.

PMID- 12204173
TI  - The psychoanalytic method and its borders: the interface with the outside world.

PMID- 12204174
TI  - Gender and psychoanalytic method.

PMID- 12204175
TI  - El impacto de nuevas tecnicas y nuevas "realidades" en psicoanalisis [The impact
      of new technologies and new realities in psychoanalysis].

PMID- 12204176
TI  - A critical enquiry into the psychoanalytic theories and approaches to
      psychosomatic conditions.

PMID- 12204177
TI  - Authority in the analytic relationship.

PMID- 12204178
TI  - As to the paper of Richard Skues ("On the dating of the aliquis slip", IJP, 2001,
      pp. 1185-1204).

PMID- 12204181
TI  - Treatment of adults with community-acquired respiratory tract infections: results
      of a multicentric clinical trial with gatifloxacin.
AB  - Respiratory tract infections have an important clinical and economic impact and
      they are the most common indication for antibiotic use in outpatient practice.
      This prospective, multicenter non-controlled trial assessed the efficacy and
      safety of gatifloxacin in the treatment of community-acquired respiratory tract
      infections. Patients were treated with a daily oral dose of gatifloxacin 400 mg
      for 7-14 days. The diagnosis of respiratory infection was made based on the
      clinical condition and/or radiologic findings. A total of 5,044 adult patients
      with community-acquired respiratory infections was treated with gatifloxacin in
      different centers in Brazil between March 1, 2001, and October 31, 2001. Among
      the 5,044 patients treated, 1,501 patients (29.76%) had community-acquired
      pneumonia, 756 (14.99%) had acute exacerbation of chronic bronchitis and 2,787
      (55.25%) had acute sinusitis. Of the total of patients treated, 3,607 (71.51%)
      were considered cured, 1,261 (25%) progressed with some clinical improvement, 28
      (0.56%) presented a relapse, 56 (1.11%) failed to treatment and 92 (1.82%) were
      unable to be evaluated. Adverse events were described in 634 (12.57%) patients.
      The most common adverse events were: nausea (2.24%); dyspepsia (1.86%); diarrhea
      (0.79%); change in taste (0.46%); insomnia and irritability (0.22%); dizziness
      (0.77%); headache (0.42%); allergic reaction (0.18%); Central Nervous System
      alterations   insomnia, agitation, anxiety   (0.46%). This study showed that the
      treatment of respiratory tract infections with gatifloxacin was safe and
      efficient and had a low incidence of adverse events.

PMID- 12204182
TI  - Effectiveness, safety and tolerability of gatifloxacin, a new 8
      methoxyfluoroquinolone, in the treatment of outpatients with community-acquired
      pneumonia: a Brazilian study.
AB  - OBJECTIVES: Evaluation of the effectiveness, safety and tolerability of
      gatifloxacin in the treatment of outpatients with community-acquired pneumonia
      (CAP). STUDY DESIGN: A prospective, multicenter, non-comparative clinical study
      carried out in Brazil. Voluntary, unpaid physician participation contributed to
      an unbiased study design. PATIENTS: Adult outpatients with clinical diagnosis of
      CAP. REGIMEN: Gatifloxacin, 400 mg PO once daily for 7 to 14 days. STUDY
      PROCEDURES: Initial clinical assessment, at the first day of gatifloxacin
      therapy; final evaluation after 7 to 14 days of treatment. RESULTS: According to
      the physicians assessments 97.3% of patients were cured or improved after
      gatifloxacin treatment. The incidence of adverse events was low and the most
      commonly reported events were nausea and dyspepsia. CONCLUSIONS: Gatifloxacin,
      400 mg PO once daily for 7 to 14 days, is effective and safe in the treatment of
      patients with CAP.

PMID- 12204183
TI  - Predictors of undetectable plasma viral load in HIV-positive adults receiving
      antiretroviral therapy in Southern Brazil.
AB  - Factors associated with undetectable viral load (<80 copies/ml) were investigated
      among non-pregnant adults in antiretroviral treatment in a specialized service
      for HIV/AIDS in Southern Brazil. Use of antiretrovirals was investigated in two
      interviews (one month interval). Clinical data were collected from the clinical
      records; viral load previous to adherence measurement was defined the viral load
      previous to the first interview; the final viral load, the viral load subsequent
      to the second interview (interval between measures approximately 6 months).
      Undetectable final viral load occurred in 48% of the patients and was positively
      associated with levels of treatment adherence (p<0.001), being 19% for less than
      60% of adherence and about 60% for adherence greater than 80%. In the
      multivariate model, the odds of undetectable final viral load was four times
      greater for 80-94% and > or =95% of adherence (CI 95% 1,80-13,28; CI 95% 1,73
      9,53), compared with less than 60% adherence; it was greater for less than 6
      months in treatment (OR = 3.37; CI 95% 1.09-10.46); and smaller for viral load
      previous to adherence measurement 5.2 log10 (OR = 0.19; CI95% 0.06-0.58),
      adjusted for these variables and sex, age, clinical status, current immune
      status, group of drugs and interval between the two measurements of viral load.
      The crude odds were lower for age 16-24 years and use of Nucleoside Analog
      Reverse Transcriptase Inhibitors only, but these effects were not significant in
      the multivariate model. There was no evidence of effect of sex, clinical status,
      current immune status, and changes in treatment regimen. Treatment adherence gave
      the largest effect. Motivational interventions directed at adherence may improve
      treatment effectiveness.

PMID- 12204184
TI  - Tattoos and transfusion-transmitted disease risk: implications for the screening
      of blood donors in Brazil.
AB  - Having a tattoo has been associated with serological evidence of hepatitis B and
      C viruses, as well as human immunodeficiency virus infections and syphilis; all
      of these are known to be transmissible by blood transfusion. These associations
      are of higher magnitude for individuals with nonprofessionally-applied tattoos
      and with two or more tattoos. Tattoos are common among drug addicts and
      prisoners, conditions that are also associated with transfusion-transmitted
      diseases. We examined the implications of these associations for the screening of
      blood donors in Brazil. Numbers of individuals who would be correctly or
      unnecessarily deferred from blood donation on the basis of the presence of
      tattoos, and on their number and type, were calculated for different prevalence
      situations based on published odds ratios. If having a tattoo was made a deferral
      criterion, cost savings (due to a reduced need for laboratory testing and
      subsequent follow-up) would accrue at the expense of the deferral of appropriate
      donors. Restricting deferral to more  at-risk  sub-groups of tattooed individuals
      would correctly defer less individuals and would also reduce the numbers of
      potential donors unnecessarily deferred. Key factors in balancing cost savings
      and unnecessary deferrals include the magnitude of the pool of blood donors in
      the population, the prevalence of individuals with tattoos and the  culture  of
      tattoos in the population. Tattoos can therefore be an efficient criterion for
      the screening of blood donors in certain settings, a finding that requires
      corroboration from larger population-based studies.

PMID- 12204185
TI  - The application of latent class analysis for diagnostic test validation of
      chronic Trypanosoma cruzi infection in blood donors.
AB  - The main strategy to prevent transfusion-associated Chagas  disease is the
      identification of T. cruzi-infected blood donors by serological screening tests,
      however there is no perfect serological gold standard. We evaluated an enzyme
      immunoassay (EIA), an indirect hemaglutination (IHA), and an indirect
      immunofluorescence (IIF) test for detecting T. cruzi antibodies in Brazilian
      blood donors. The results were submitted to latent class analysis, and a
      radioimmunopreciptation (RIPA) test was performed on repeatedly positive samples.
      Among 1951 donors, 11 (0.56%) were positive by EIA, 6 (0.31%) by IHA and 16
      (0.82%) by IIF. Six samples were positive with all tests, while 4 reacted with
      EIA and IIF. The RIPA was positive in 6 (75.0%), 7 (66.6%), and 4 (54.0%) samples
      reacting by the EIA, IHA and IIF tests, respectively. The latent class model
      detected a high sensitivity rate (100%) for the EIA and IIF, and a specificity
      rate of 99.95% and 99.69% for the EIA and IIF tests, respectively. The
      probability of being case according to the model was 99.92% when both EIA and IIF
      were positive, and 100% for the association of EIA, IIF, and IHA.

PMID- 12204186
TI  - Pulmonary alveolar proteinosis and tuberculosis in a diabetic patient: a rare or
      a seldom diagnosed association?
AB  - A case of Pulmonary Alveolar Proteinosis (PAP), in association with tuberculosis,
      is described in a 35-year-old diabetic patient. Lung biopsy showed an intra
      alveolar accumulation of PAS-positive material, and multifocal granulomas
      compatible with tuberculosis. The bronchoalveolar culture was positive for
      Mycobacterium tuberculosis. PAP results from an imbalance of the mechanisms that
      regulate the homeostasis of the surfactant, where specific proteins are involved,
      especially SP-A and SP-D, the cytokines, IL-10 and GM-CSF, in addition to
      alveolar macrophages and type-II pneumocytes. Chemotaxis and phagocytic capacity
      are reduced. PAP and diabetes share several immunological disfunctions that may
      increase the risk for tuberculosis. Although there are no controlled studies, the
      diagnosis of PAP in diabetic patients with tuberculosis must be considered.

PMID- 12204187
TI  - Uncommon vancomycin-induced side effects.
AB  - Vancomycin has been used with increased frequency during the past 15 years and
      the most common toxicity with this drug is the  red man syndrome . Other adverse
      effects include neutropenia, fever, phlebitis, nephrotoxicity, ototoxicity,
      thrombocytopenia, interstitial nephritis, lacrimation, linear IgA bullous
      dermatosis, necrotizing cutaneous vasculitis and toxic epidermal necrolysis. Only
      two cases of vancomycin-induced Stevens-Johnson syndrome and one case of
      pancytopenia have been reported in the medical literature. The treatment for both
      situations is based on cessation of the vancomycin therapy; in cases of Stevens
      Johnson syndrome, antihistamine and/or steroid agents can be used. This article
      reports a case of pancytopenia and a case of erythema major associated with
      neutropenia.

PMID- 12204188
TI  - Toxoplasmic encephalitis in an HIV infected pregnant woman: successful outcome
      for both mother and child.
AB  - This report describes a case of Toxoplasma encephalitis during pregnancy of an
      HIV infected woman who was severely immunosuppressed (CD(4): 17 cells/mm3), had a
      high viral load (RNA PCR:230,000 copies/ml), was treated with sulfadiazine,
      pyrimethamine and folinic acid for toxoplasmosis and was being treated with
      highly potent antiretroviral drugs (AZT, 3TC and nelfinavir) for HIV infection.
      The newborn was born through an elective C-section, received six weeks of AZT
      according to the 076 protocol and was clinically normal at birth. Subsequently he
      had two RNA PCR negatives for HIV, seroreverted and had no clinical or laboratory
      evidence of congenital toxoplasmosis. Despite the concerns of the use of these
      combined therapies on the foetus during pregnancy, their efficacy illustrates
      that keeping the mother alive and in good health is an important strategy to
      protect the unborn child from acquiring these two infections.

PMID- 12204189
TI  - Multiple neural systems controlling food intake and body weight.
AB  - Discovery of the leptin receptor and its downstream peptidergic pathways has
      reconfirmed the crucial role of the hypothalamus in the regulation of food intake
      and energy balance. Strategically located in the midst of the mammalian neuraxis,
      the hypothalamus receives at least three distinct types of relevant information
      via direct or indirect neural connections as well as hormone receptors and
      substrate sensors bestowed on hypothalamic neurons. First, the medial and to a
      lesser extent the lateral hypothalamus receive a rich mix of information
      pertaining to the internal state of relative energy repletion/depletion. Second,
      specific hypothalamic nuclei receive information about the behavioral state, such
      as diurnal clock, physical activity-level, reproductive cycle, developmental
      stage, as well as imminent (e.g. fight and flight) and chronic (e.g. infection)
      stressors, that can potentially impact on short-term availability of fuels and
      long-term energy balance. Third, the hypothalamus, particularly its lateral
      aspects, receives information from areas in the forebrain involved in the
      acquisition, storage, and retrieval of sensory representations of the external
      food space and internal food experience, as well as from the executive forebrain
      involved in behavior selection and initiation. In addition, rich
      intrahypothalamic connections facilitate further distribution of incoming
      information to various hypothalamic nuclei. On the other hand, the hypothalamus
      has widespread neural projections to the same cortical areas it receives inputs,
      and many hypothalamic neurons are one synapse away from most endocrine systems
      and from both sympathetic and parasympathetic effector organs involved in the
      flux, storage, mobilization, and utilization of fuels. It is argued that
      processing within cortico-limbic areas and communication with hypothalamic areas
      are particularly important in human food intake control that is more and more
      guided by cognitive rather than metabolic aspects in the obesigenic environment
      of affluent societies. A distributed neural network for the control of food
      intake and energy balance consisting of a central processor and several parallel
      processing loops is hypothesized. Detailed neurochemical, anatomical, and
      functional analysis of reciprocal connections of the numerous peptidergic neuron
      populations in the hypothalamus with extrahypothalamic brain areas will be
      necessary to better understand what hypothalamus, forebrain, and brainstem tell
      each other and who is in charge under specific conditions of internal and
      external nutrient availability.

PMID- 12204190
TI  - The discriminative stimulus effects of pentylenetetrazol as a model of anxiety:
      recent developments.
AB  - Pentylenetetrazol (PTZ), a GABA(A) receptor antagonist and prototypical
      anxiogenic drug, has been extensively utilized in animal models of anxiety. PTZ
      produces a reliable discriminative stimulus which is largely mediated by the
      GABA(A) receptor. Several classes of compounds can modulate the PTZ
      discriminative stimulus including 5-HT(1A), 5-HT(3), NMDA, glycine, and L-type
      calcium channel ligands. Spontaneous PTZ-lever responding is seen in trained rats
      during withdrawal from GABA(A) receptor compounds such as chlordiazepoxide and
      diazepam, and also ethanol, morphine, nicotine, cocaine, haloperidol, and
      phencyclidine. This effect is largely mediated by the GABA(A) receptor, which
      suggests that anxiety may be part of a generalized withdrawal syndrome mediated
      by the GABA(A) receptor. There are also important hormonal influences on PTZ.
      Corticosterone plays some role in mediation of its anxiogenic effects. There is a
      marked sex difference in response to the discriminative stimulus effects of PTZ,
      and estrogens appear to protect against its anxiogenic effects. Further work with
      the PTZ drug discrimination is warranted for characterization of anxiety during
      withdrawal, and the hormonal mechanisms of anxiety.

PMID- 12204191
TI  - Integrative role for serotonergic and glutamatergic receptor mechanisms in the
      action of NMDA antagonists: potential relationships to antipsychotic drug actions
      on NMDA antagonist responsiveness.
AB  - NMDA receptor antagonists worsen symptoms in schizophrenia and induce
      schizophrenic-like symptoms in normal individuals. In animals, NMDA antagonist
      induced behavioral responses include increased activity, head weaving, deficits
      in paired pulse inhibition and social interaction, and increased forced swim
      immobility. Repeated exposure to NMDA antagonists in animals results in
      behavioral sensitization-a phenomenon accentuated in rats with dopaminergic
      neurons lesioned during development. In keeping with an involvement of serotonin
      and glutamate release in NMDA antagonist action, selected behaviors induced by
      NMDA antagonists are minimized by 5-HT(2A) receptor antagonists and mGLU2
      receptor agonists. These observations provide promising new approaches for
      treating acute NMDA antagonist-induced psychosis. Further, acute atypical
      antipsychotic drugs also minimize NMDA antagonist actions to a greater degree
      than typical antipsychotics. However, because knowledge concerning acute versus
      chronic effectiveness of various antipsychotic drugs against NMDA antagonist
      neuropathology is limited, future studies to define more fully the basis of their
      differences in efficacy after chronic treatment could provide an understanding of
      their actions on neural mechanisms responsible for the core pathogenesis of
      schizophrenia.

PMID- 12204192
TI  - The role of prenatal stress in the etiology of developmental behavioural
      disorders.
AB  - Substantial evidence from preclinical laboratory studies indicates that prenatal
      stress (PS) affects the hormonal and behavioural development of offspring. In the
      following review, the effects of PS in rodents and non-human primates on
      hypothalamic-pituitary-adrenal (HPA) reactivity to stress, morphological changes
      in the brain, motor behaviour and learning are surveyed. PS has been found to
      alter baseline and stress-induced responsivity of the HPA axis and levels and
      distribution of regulatory neurotransmitters, such as norepinepherine, dopamine,
      serotonin and acetylcholine and to modify key limbic structures. In rodents and
      non-human primates, PS affected learning, anxiety and social behaviour. The
      relevance of these findings to humans is discussed with respect to (a) the effect
      of administration of exogenous corticosteroids in pregnancy and (b) maternal
      state and trait anxiety during gestation and its relation to foetal autonomic
      regulation as putative predisposing factors in the pathogenesis of behavioural
      developmental delays in children.

PMID- 12204193
TI  - Effects of prenatal protein malnutrition on the hippocampal formation.
AB  - In this review we have assessed the effects of prenatal protein malnutrition on
      the hippocampal formation of the developing brain. In investigating this insult
      in the hippocampal neuronal model we have concentrated on aspects of enhanced
      inhibition we have shown in our earlier studies. Since this involves particular
      attention to the GABAergic interneurons we have examined the complex
      interneuronal networks of the hippocampal formation and their neurotransmitter
      afferent inputs, particularly the serotonergic system from the midbrain raphe
      nuclei. A variety of combinations of specialized interneurons are discussed in
      terms of how malnutrition insults perturb function in these inhibitory and
      disinhibitory networks. Pathological enhancement of inhibition manifests itself
      by diminished plasticity, alterations in theta activity and deficits in long-term
      learning behaviors. Long-term inhibition in select GABA interneuron systems may
      form a major derangement seen following prenatal protein malnutrition. The focus
      of this study is to relate enhanced inhibition to the several forms of inhibitory
      systems present in the hippocampal formation and develop hypotheses as to the
      primary derangements that may account for pathological inhibition in prenatal
      malnutrition.

PMID- 12204194
TI  - The temporal organization of ingestive behaviour and its interaction with
      regulation of energy balance.
AB  - Body weight of man and animals is under homeostatic control mediated by the
      adjustment of food intake. It is discussed in this review that besides signals
      reporting energy deficits, optimized programs of body clocks take part in feeding
      behaviour as well. Circadian light- and food-entrainable clocks determine
      anticipatory adaptive behavioural and physiological mechanisms, promoting or
      inhibiting food intake. In fact these clocks form the constraints within which
      the homeostatic regulation of feeding behaviour is operating. Therefore, a strong
      interaction between circadian and homeostatic regulation must occur. In this
      homeostatic control, a wide variety of regulatory negative feedback mechanisms,
      or satiety signals, play a dominant role. In this respect several gut hormones
      and body temperature function as 'short-term' satiety factors and determine meal
      sizes and intermeal intervals. Leptin, secreted by fat cells in proportion to the
      size of adipose tissue mass, is probably an important determinant of the 'long
      term' regulation of feeding behaviour by setting the motivational background
      level for feeding behaviour. Thus, initiation or termination of meals at any
      particular point in time, depends on the resultant of all satiety signals and on
      constraints imposed by circadian light- and food-entrainable oscillators.

PMID- 12204195
TI  - Sigma(1) (sigma(1)) receptor antagonists represent a new strategy against cocaine
      addiction and toxicity.
AB  - Cocaine is a highly addictive substance abused worldwide. Its mechanism of action
      involves initially inhibition of neuronal monoamine transporters in precise brain
      structures and primarily the dopamine reuptake system located on mesolimbic
      neurons. Cocaine rapidly increases the dopaminergic neurotransmission and
      triggers adaptive changes in numerous neuronal circuits underlying reinforcement,
      reward, sensitization and the high addictive potential of cocaine. Current
      therapeutic strategies focus on counteracting the cocaine effects directly on the
      dopamine transporter, through post-synaptic D(1), D(2) or D(3) receptors or
      through the glutamatergic, serotoninergic, opioid or corticotropin-releasing
      hormone systems. However, cocaine administration also results in the activation
      of numerous particular targets. Among them, the sigma(1) (sigma(1)) receptor is
      involved in several acute or chronic effects of cocaine. The present review will
      first bring concise overviews of the present strategies followed to alleviate
      cocaine addiction and animal models developed to analyze the pharmacology of
      cocaine addiction. Evidence involving activation of the sigma(1) receptor in the
      different aspects of cocaine abuse, will then be detailed, following acute,
      repeated, or overdose administration. The therapeutic potentials and
      neuropharmacological perspectives opened by the use of selective sigma(1)
      receptor antagonists in cocaine addiction will finally be discussed.

PMID- 12204196
TI  - Targeted "knockdown" of channel expression in vivo with an antisense morpholino
      oligonucleotide.
AB  - We have examined whether antisense morpholino oligonucleotides (morpholinos) can
      be used as a tool to suppress or "knockdown" the expression of ion channels
      during development of the zebrafish. Because the acetylcholine receptor channel
      is well characterized in zebrafish and is abundant as skeletal muscle is found
      throughout the body, we sought to knock down its expression as a general test of
      the feasibility of this approach. A 25-mer morpholino was designed to target the
      5' region of the cloned alpha-subunit and was injected into early stage blastulae
      in order to trap it in all developing cells. From the time of hatching (early on
      the third day of development) and for a few days after, a fraction of the
      injected embryos were immobile, i.e. were "morphant". Injection of blastulae
      without the morpholino or with a control morpholino containing four mispaired
      bases did not affect the embryos. Although the morphant embryos were generally
      normal in appearance, they lacked staining with alpha-bungarotoxin or an alpha
      subunit-specific monoclonal antibody. In whole muscle cell recordings from
      morphant embryos, miniature end-plate potentials were undetectable in many of the
      cells and in most they had a slower, immature time course. These results are
      consistent with a greatly reduced, dysfunctional level of expression of
      acetylcholine receptors in morphant embryos. Because of their stability and
      specificity, morpholinos should prove useful for targeted deletion of transmitter
      receptors and channels in developing zebrafish and possibly in other
      preparations.

PMID- 12204197
TI  - Glial cell plasticity in sensory ganglia induced by nerve damage.
AB  - Numerous studies have been done on the effect of nerve injury on neurons of
      sensory ganglia but little is known about the contribution of satellite glial
      cells (SCs) in these ganglia to post-injury events. We investigated cell-to-cell
      coupling and ultrastructure of SCs in mouse dorsal root ganglia after nerve
      injury (axotomy). Under control conditions SCs were mutually coupled, but mainly
      to other SCs around a given neuron. After axotomy SCs became extensively coupled
      to SCs that enveloped other neurons, apparently by gap junctions. Serial section
      electron microscopy showed that after axotomy SC sheaths enveloping neighboring
      neurons formed connections with each other. Such connections were absent in
      control ganglia. The number of gap junctions between SCs increased 6.5-fold after
      axotomy. We propose that axotomy induces growth of perineuronal SC sheaths,
      leading to contacts between SCs enveloping adjacent neurons and to formation of
      new gap junctions between SCs. These changes may be an important mode of glial
      plasticity and can contribute to neuropathic pain.

PMID- 12204198
TI  - Impaired hypoxic tolerance and altered protein binding of NADH in presymptomatic
      APP23 transgenic mice.
AB  - It is being discussed whether impairment of energy metabolism is a final common
      pathway of neurodegeneration or initiates the neurodegenerative cascade. The goal
      was to investigate hypoxic tolerance and oxidative energy metabolism in 4-month
      old, presymptomatic B6-Tg(ThylAPP)23Sdz (APP23) mice, a transgenic mouse model of
      Alzheimer's disease. Posthypoxic recovery of the population spike amplitude in
      hippocampal region CA1 upon stimulation of Schaffer collaterals in region CA3 (15
      min hypoxia, 45 min recovery) was 43+/-46% (mean+/-S.D.) vs. 19+/-35% (P<0.05) in
      slices from wild-type and transgenic animals, respectively. Fluorescence lifetime
      sensitive spectroscopy of NADH in the CA1 pyramidal cell layer (gate set for
      detection of protein-bound NADH) showed a wavelength maximum at 455.3+/-1.6 nm
      (mean+/-S.D.) in controls and 453.5+/-2.4 nm (P<0.05) in mutants. We conclude
      that hypoxic tolerance is impaired in presymptomatic APP23 mice and occurs prior
      to extracellular deposition of amyloid plaques. Impaired energy metabolism may
      thus partake in initiating the neurodegenerative cascade in a transgenic model of
      Alzheimer's disease. The blue shift of the spectrum of NADH in mutant mice
      indicates an altered protein microenvironment of energy metabolism under control
      conditions.

PMID- 12204199
TI  - Role of primary afferent nerves in allodynia caused by diabetic neuropathy in
      rats.
AB  - Both myelinated and unmyelinated afferents are implicated in transmitting
      diabetic neuropathic pain. Although unmyelinated afferents are generally
      considered to play a significant role in diabetic neuropathic pain, pathological
      changes in diabetic neuropathy occur mostly in myelinated A-fibers. In the
      present study, we first examined the role of capsaicin-sensitive C-fibers in the
      development of allodynia induced by diabetic neuropathy. We then studied the
      functional changes of afferent nerves pertinent to diabetic neuropathic pain.
      Diabetes was induced in rats by i.p. streptozotocin. To deplete capsaicin
      sensitive C-fibers, rats were treated with i.p. resiniferatoxin (300 microg/kg).
      Mechanical and thermal sensitivities were measured using von Frey filaments and a
      radiant heat stimulus. Single-unit activity of afferents was recorded from the
      tibial nerve. Tactile allodynia, but not thermal hyperalgesia, developed in
      diabetic rats. Resiniferatoxin treatment did not alter significantly the degree
      and time course of allodynia. Post-treatment with resiniferatoxin also failed to
      attenuate allodynia in diabetic rats. The electrophysiological recordings
      revealed ectopic discharges and a higher spontaneous activity mainly in Adelta-
      and Abeta-fiber afferents in diabetic rats regardless of resiniferatoxin
      treatment. Furthermore, these afferent fibers had a lower threshold for
      activation and augmented responses to mechanical stimuli. Thus, our study
      suggests that capsaicin-sensitive C-fiber afferents are not required in the
      development of allodynia in this rat model of diabetes. Our electrophysiological
      data provide substantial new evidence that the abnormal sensory input from Adelta
      and Abeta-fiber afferents may play an important role in diabetic neuropathic
      pain.

PMID- 12204200
TI  - Ontogeny of calmodulin gene expression in rat brain.
AB  - Calmodulin (CaM), a multifunctional intracellular calcium receptor, is a key
      element in signaling mechanisms. It is encoded in vertebrates by multiple
      apparently redundant genes (CaM I, II, III). To investigate whether differential
      expression takes place in the developing rat brain, a quantitative in situ
      hybridization analysis was carried out involving 15 brain areas at six ages
      between embryonic day 19 and postnatal day 20 (PD20) with gene-specific
      [(35)S]cRNA probes. A widespread, developmental stage-specific and differential
      expression of the three CaM genes was observed. The characteristic changes in the
      CaM mRNA levels in the examined time frame allowed the brain regions to be
      classified into three categories. For the majority of the areas (e.g. the
      piriform cortex for CaM III), the signal intensities peaked at around PD10 and
      the expression profile was symmetric (type 1). Other regions (e.g. the cerebral
      cortex, layer 1 for CaM II) displayed their highest signal intensities at the
      earliest age measured, followed by a gradual decrease (type 2). The signal
      intensities in the regions in the third group (e.g. the hypothalamus for CaM III)
      fluctuated from age to age (type 3). Marked CaM mRNA levels were measured for
      each transcript corresponding to the three CaM genes in the molecular layers of
      the cerebral and cerebellar cortici and hippocampus, suggesting their dendritic
      translocation. The highest signal intensity was measured for CaM II mRNA,
      followed by those for CaM III and CaM I mRNAs on PD1. However, the CaM II and CaM
      III mRNAs subsequently decreased steeply, while the CaM I mRNAs were readily
      detected even on PD20. Our results suggest that during development (1) the
      transcription of the CaM genes is under differential, area-specific control, and
      (2) a large population of CaM mRNAs is targeted to the dendritic compartment in a
      gene-specific manner.

PMID- 12204201
TI  - Asymmetrical changes of excitatory synaptic transmission in dopamine-denervated
      striatum after transient forebrain ischemia.
AB  - Spiny neurons in the neostriatum are highly vulnerable to cerebral ischemia.
      Recent studies have shown that the postischemic cell death in the right striatum
      was reduced after ipsilateral dopamine denervation whereas no protection was
      observed in the left striatum after dopamine denervation in the left side. In
      order to reveal the mechanisms of such asymmetrical protection,
      electrophysiological changes of dopamine-denervated striatal neurons were
      compared after ischemia between the left and right striatum using intracellular
      recording and staining techniques in vivo. No difference in cortically evoked
      initial excitatory postsynaptic potentials was found between the left and right
      striatum in intact animals after ipsilateral dopamine denervation. The initial
      excitatory postsynaptic potentials in the dopamine-denervated right striatum were
      suppressed after transient forebrain ischemia while no significant changes were
      found in the dopamine-denervated left striatum. Paired-pulse tests suggested that
      these changes involved presynaptic mechanisms. Although the incidence of a late
      depolarizing postsynaptic potential elicited by cortical stimulation increased
      after ischemia in both sides, the increase was greater in the left side. The
      analysis of current-voltage relationship of spiny neurons indicated that inward
      rectification in the left striatum transiently disappeared shortly after ischemia
      whereas that in the right side remained unchanged. The intrinsic excitability of
      spiny neurons in both sides were suppressed after ischemia, however, the
      suppression in the right side was stronger than in the left side. The above
      results demonstrate that after ipsilateral dopamine denervation, the depression
      of excitatory synaptic transmission and neuronal excitability in the right
      striatum is more severe than that in the left striatum following ischemia. The
      depression of excitatory synaptic transmission and neuronal excitability,
      therefore, might play an important role in neural protection after ischemic
      insult.

PMID- 12204202
TI  - Time course and manner of Purkinje neuron death following a single ethanol
      exposure on postnatal day 4 in the developing rat.
AB  - The present study was designed to evaluate the time course and manner of Purkinje
      cell death following a single ethanol dose delivered intragastrically on
      postnatal day (PN) 4 to rat pups. Analysis included immunolabeling of Purkinje
      cells with antibody specific for calbindin D28k and counting of Purkinje cells in
      each lobule of a mid-vermal slice. Terminal deoxynucleotidyl transferase-mediated
      dUTP nick-end labeling analysis and immunodetection for cleaved (activated)
      caspase-3 enzyme was used to identify apoptosis, with calbindin D28k co
      immunolabeling to identify apoptotic Purkinje cells. Finally, immunodetection for
      cytochrome c, again with co-labeling using calbindin D28k antibody, identified
      intracellular release of cytochrome c from the mitochondria into the cytoplasm of
      Purkinje cells. The data demonstrate that a single dose of ethanol results in a
      significant and extensive, lobular dependent loss of Purkinje cells within 24 h
      after administration. Extensive loss in the early developing lobules (I-III, VIII
      X) and less to no loss in the later developing lobules (IV-VII) is consistent
      with prior literature reports on the ethanol-induced effects on Purkinje cells at
      this age. Clear and consistent evidence of apoptotic Purkinje cells was
      identified and the pattern was transient in nature. Finally, cytochrome c is
      released from the mitochondria of Purkinje cells in a time course consistent with
      the activation of the mitochondrial pathway of apoptosis. These data support the
      hypothesis that ethanol-induced loss of Purkinje cells involves apoptotic
      mechanisms. Furthermore, the initiation of apoptosis by ethanol is consistent
      with ethanol-induced interruptions of Purkinje cell neurotrophic support leading
      to activation of the mitochondrial pathway of apoptosis.

PMID- 12204203
TI  - Estrogen modulates myometrium-induced sympathetic neurite formation through
      actions on target and ganglion.
AB  - Estrogen induces rapid and extensive degeneration of rodent uterine myometrial
      sympathetic innervation. To clarify the underlying mechanisms, we used explant
      cultures to assess whether estrogen affects the myometrium's ability to induce
      sympathetic neuritogenesis and the sympathetic neuron's ability to respond.
      Superior cervical ganglion explants from ovariectomized adult donors extended
      neurites when cultured alone in serum-free medium, and their numbers increased
      2.3-fold in the presence of myometrial explants from ovariectomized adult rats.
      The myometrium's ability to induce neuritogenesis was abolished by injection of
      myometrium donors with 17beta-estradiol 24 h prior to tissue harvest. Myometrial
      neurite-promoting effects were also abolished by adding 2x10(-8)M estradiol to
      the culture medium. Because outgrowth from ganglia of ovariectomized rats
      cultured alone was not affected by estrogen in the culture medium, this indicates
      that estrogen acts directly on myometrium to abrogate its neurite-promoting
      effects. However, estrogen injection of ganglion donor rats also inhibited
      neurite extension toward ovariectomized myometrium, suggesting that some factor
      in ovariectomized rats normally acts on the ganglion to prevent estrogen from
      inhibiting neurite outgrowth. When ganglia from hypophysectomized ovariectomized
      donors were cultured alone, neuritogenesis was normal but estrogen added to the
      culture medium now attenuated outgrowth. Prolactin but not other pituitary
      derived hormones reversed the suppression of neuritogenesis induced by estrogen.
      We conclude that estrogen acts directly on myometrium to inhibit its neuritogenic
      effects on sympathetic neurons. Estrogen can also attenuate neurite formation by
      acting directly on the ganglion; this effect normally is not apparent at low
      estrogen levels because a pituitary hormone (possibly prolactin) prevents the
      ganglion from responding fully to estrogen. With high in vivo estrogen, this
      pituitary hormone's effects are abated, possibly through diminished release, and
      estrogen directly reduces ganglion neuritogenesis. Thus, estrogen regulates
      uterine sympathetic nerve remodeling through actions on myometrium, ganglion, and
      intermediary pituitary factors.

PMID- 12204204
TI  - Quantitative analysis of the dendritic morphology of corticocortical projection
      neurons in the macaque monkey association cortex.
AB  - The polymodal association areas of the primate cerebral cortex are heavily
      interconnected and play a crucial role in cognition. Area 46 of the prefrontal
      cortex in non-human primates receives direct inputs from several association
      areas, among them the cortical regions lining the superior temporal sulcus. We
      examined whether projection neurons providing such a corticocortical projection
      differ in their dendritic morphology from pyramidal neurons projecting locally
      within area 46. Specific sets of corticocortical projection neurons were
      identified by in vivo retrograde transport in young macaque monkeys. Full
      dendritic arbors of retrogradely labeled neurons were visualized in brain slices
      by targeted intracellular injection of Lucifer Yellow, and reconstructed three
      dimensionally using computer-assisted morphometry. Total dendritic length,
      numbers of segments, numbers of spines, and spine density were analyzed in layer
      III pyramidal neurons forming long projections (from the superior temporal cortex
      to prefrontal area 46), as well as local projections (within area 46). Sholl
      analysis was also used to compare the complexity of these two groups of neurons.
      Our results demonstrate that long corticocortical projection neurons connecting
      the temporal and prefrontal cortex have longer, more complex dendritic arbors and
      more spines than pyramidal neurons projecting locally within area 46. The more
      complex dendritic arborization of such neurons is likely linked to their
      participation in cortical networks that require extensive convergence of multiple
      afferents at the cellular level.

PMID- 12204205
TI  - Lipopolysaccharide prevents cell death caused by glutathione depletion: possible
      mechanisms of protection.
AB  - Glutathione is an important cellular antioxidant present at high concentrations
      in the brain. We have previously demonstrated that depletion of glutathione in
      mesencephalic cultures results in cell death and that the presence of glia is
      necessary for the expression of toxicity. Cell death following glutathione
      depletion can be prevented by inhibition of lipoxygenase activity, implicating
      arachidonic acid metabolism in the toxic events. In this study we examined the
      effect of glial activation, known to cause secretion of cytokines and release of
      arachidonic acid, on the toxicity induced by glutathione depletion. Our data show
      that treatment with the endotoxin lipopolysaccharide activated glial cells in
      mesencephalic cultures, increased interleukin-1beta in microglia and caused
      depletion of glutathione. The overall effect of lipopolysaccharide treatment,
      however, was protection from damage caused by glutathione depletion. Addition of
      cytokines or growth factors, normally secreted by activated glia, did not modify
      L-buthionine sulfoximine toxicity, although basic fibroblast growth factor
      provided some protection. A large increase in the protein content and the
      activity of Mn-superoxide dismutase, observed after lipopolysaccharide treatment,
      may indicate a role for this mitochondrial antioxidant enzyme in the protective
      effect of lipopolysaccharide. This was supported by the suppression of toxicity
      by exogenous superoxide dismutase. Our data suggest that superoxide contributes
      to the damage caused by glutathione depletion and that up-regulation of
      superoxide dismutase may offer protection in neurodegenerative diseases
      associated with glutathione depletion and oxidative stress.

PMID- 12204206
TI  - Dissociation of septo-hippocampal metabolism in the congenitally helpless rat.
AB  - Congenitally helpless rats, selectively bred to model features of endogenous
      depression, appear to have a paraventricular hypothalamic nucleus (PVH) that is
      markedly hyperactive. This study investigated septal and hippocampal regions
      purported to regulate the PVH. We found that cytochrome oxidase, an index of
      oxidative metabolism and neural activity, was significantly elevated in the
      hippocampus and subiculum of congenitally helpless rats. However, reduced
      activity was observed in the lateral and medial septal nuclei, the nucleus of the
      diagonal band, and the bed nucleus of the stria terminalis. This dissociation
      between hippocampal and septal activity may be a predisposing factor for the
      development of helpless behavior.

PMID- 12204207
TI  - Enhanced release of adenosine in rat hind paw following spinal nerve ligation:
      involvement of capsaicin-sensitive sensory afferents.
AB  - Modulation of endogenous adenosine levels by inhibition of adenosine metabolism
      produces a peripheral antinociceptive effect in a neuropathic pain model. The
      present study used microdialysis to investigate the neuronal mechanisms
      modulating extracellular adenosine levels in the rat hind paw following tight
      ligation of the L5 and L6 spinal nerves. Subcutaneous injection of 50 microl
      saline into the nerve-injured paw induced a rapid and short-lasting increase in
      extracellular adenosine levels in the subcutaneous tissues of the rat hind paw
      ipsilateral to the nerve injury. Saline injection did not increase adenosine
      levels in sham-operated rats or non-treated rats. The adenosine kinase inhibitor
      5'-amino-5'-deoxyadenosine and the adenosine deaminase inhibitor 2'
      deoxycoformycin, at doses producing a peripheral antinociceptive effect, did not
      further enhance subcutaneous adenosine levels in the nerve-injured paw. Systemic
      pretreatment with capsaicin, a neurotoxin selective for small-diameter sensory
      afferents, markedly reduced the saline-evoked release of adenosine in rat hind
      paw following spinal nerve ligation. Systemic pretreatment with 6
      hydroxydopamine, a neurotoxin selective for sympathetic afferent nerves, did not
      affect release. These results suggest that following nerve injury, peripheral
      capsaicin-sensitive primary sensory afferent nerve terminals are hypersensitive,
      and are able to release adenosine following a stimulus that does not normally
      evoke release in sham-operated or intact rats. Sympathetic postganglionic
      afferents do not appear to be involved in such release. The lack of effect on
      such release by the inhibitors of adenosine metabolism suggests an altered
      peripheral adenosine system following spinal nerve ligation.

PMID- 12204208
TI  - Preservation of visual responsiveness in the superior colliculus of RCS rats
      after retinal pigment epithelium cell transplantation.
AB  - The dystrophic RCS rat undergoes progressive photoreceptor degeneration due to a
      primary defect in retinal pigment epithelial (RPE) cells. This has a major impact
      on central visual responsiveness. Here we have examined how functional
      deterioration is contained by subretinal transplantation of immortalized human
      RPE cells. Transplantation was done at three to four weeks of age prior to
      significant photoreceptor loss and recipients were kept on cyclosporin. At six
      months of age, sensitivity maps and multi-unit response properties were obtained
      across the visual field by recording at 76 equidistant sites encompassing the
      whole superior colliculus.A significant degree of functional protection, both in
      terms of area of responsive retina and response characteristics was observed
      following RPE transplantation. At best, the sensitivity, latency of onset, and
      response rise time were all maintained within normal ranges and this was achieved
      with no more than half of the normal complement of photoreceptors. Although
      partial, the degree of anatomical preservation (both in terms of outer nuclear
      layer thickness and area of rescue) correlated well with the level of preserved
      visual sensitivities. Sham injections also resulted in rescue, though the area of
      preservation was strictly confined to the needle injury site and the response
      properties were significantly worse than with RPE injections. This study shows
      that central physiological responsiveness and correlated retinal morphology can
      be preserved in an animal model of retinal disease by implantation of an
      immortalized cell line. The use of retinal sensitivity measurements provides a
      background for assessing higher visual functions in these animals and a direct
      comparison for human perimetry measures.

PMID- 12204209
TI  - Time-dependent increase in basic fibroblast growth factor protein in limbic
      regions following electroshock seizures.
AB  - Brief experimentally induced seizures have been shown to increase the expression
      of mRNA encoding basic fibroblast growth factor (FGF-2) in specific brain
      regions. However, the extent to which this change in mRNA affects the expression
      of FGF-2 protein in these brain regions has not been examined. In the present
      study, we exposed rats to brief non-injurious seizures to determine whether this
      treatment would lead to an increase in FGF-2 protein expression in selected brain
      regions. Because initial results indicated that the elevation of FGF-2 protein
      was not significant following acute seizure exposure, we examined both acute and
      chronic seizure treatment to determine whether FGF-2 protein expression could be
      increased under conditions of repeated seizures. Brief limbic seizures were
      induced by minimal electroconvulsive shock (ECS) given as daily treatments for 1
      (acute) or 7 (chronic) days. FGF-2 protein was measured in hippocampus, rhinal
      cortex, frontal cortex, and olfactory bulb at 20, 48, and 72 h following the last
      seizure. No significant increases in FGF-2 protein were observed in any region
      following acute ECS. In the chronic ECS-treated groups, significantly elevated
      FGF-2-like immunoreactivity was found in the frontal and rhinal cortex as
      compared with the same regions from both control and acute ECS animals. Increases
      after chronic ECS were maximal at 20 h, and remained significantly elevated as
      long as 72 h. These increases were predominantly observed for the 24-kDa and
      22/22.5-kDa FGF-2 isoforms. Because chronic ECS, which has been shown to be
      protective against neuronal cell death, induced significantly more FGF-2
      immunoreactivity than did acute ECS, we suggest that FGF-2 expression may be an
      important substrate for the neuroprotective action of non-injurious seizures. A
      prolonged induction of the high molecular weight isoforms of FGF-2, as occurs
      after chronic ECS, may selectively reduce the vulnerability of certain brain
      regions to a variety of neurodegenerative insults.

PMID- 12204210
TI  - The effects of repeated minimal electroconvulsive shock exposure on levels of
      mRNA encoding fibroblast growth factor-2 and nerve growth factor in limbic
      regions.
AB  - Chronic, but not acute, exposure to minimal electroconvulsive shock (ECS) has
      been shown to decrease vulnerability to neuronal cell death, without itself
      causing neuronal damage. One potential mechanism for the neuroprotective effect
      of ECS is the increase in fibroblast growth factor-2 (FGF-2) which occurs after
      chronic, but not acute, ECS exposure. This raises the possibility that repeated
      seizures over a period of several days may alter the transcriptional regulation
      of FGF-2. To test this hypothesis, the present study compared the effect of acute
      (1 day) vs. chronic (7 days) ECS treatment on levels of mRNA for FGF-2 in rhinal
      and frontal cortices, hippocampus, and olfactory bulbs. In addition, mRNA for
      another prominent neurotrophic factor, nerve growth factor (NGF), was assayed
      concurrently. At 8 h after acute ECS, mRNA levels increased by 60% for FGF-2 and
      136% for NGF in rhinal cortex, 32% for FGF-2 and 36% for NGF in frontal cortex,
      and by 13% for NGF in hippocampus. After 7 days of ECS treatment the respective
      increases were 72% and 80%, 53% and 38%, and 28%. No increases were observed in
      olfactory bulbs after either treatment regimen. The peak increases in FGF-2 mRNA
      were consistently greater after chronic treatment, but the differences from those
      seen acutely reached significance in frontal cortex only. However, the duration
      over which mRNA for FGF-2 was elevated did not differ between the acute and
      chronic ECS groups. NGF mRNA induction was neither enhanced nor prolonged as a
      result of chronic ECS as compared to acute ECS treatment. These results suggest
      that chronic ECS treatment may lead to an enhanced rate of transcription of
      message for FGF-2 but not for NGF, in selected brain regions. At the same time,
      the results indicate that chronic ECS treatment induces FGF-2 and NGF mRNA
      expression in a tissue-specific manner and that this induction is maintained over
      the 7-day treatment period. The sustained increases in mRNAs for these trophic
      factors may contribute to the neuroprotective actions of chronic ECS treatment.

PMID- 12204211
TI  - Rotational behavior and electrophysiological effects induced by GABA(B) receptor
      activation in rat globus pallidus.
AB  - GABA is the major neurotransmitter used in the globus pallidus and there is
      evidence that GABA(B) receptors exist in this nucleus. Here we show that
      unilateral microinjection of baclofen, a GABA(B) receptor agonist, induced
      ipsilateral turning in Sprague-Dawley rats. This effect was prevented by
      preinjection of the GABA(B) receptor antagonist CGP55845A, which itself did not
      cause rotation. Thus, activation of GABA(B) receptor may suppress the activity of
      globus pallidus neurons, which is in line with the finding that the glutamate
      receptor antagonists (+/-)-2-amino-5-phosphonopentanoic acid and 6-cyano-7
      nitroquinoxaline-2,3-dione also caused similar ipsilateral turning when injected
      into globus pallidus. Furthermore, in the presence of these glutamate receptor
      antagonists, injection of baclofen resulted in fewer rotations. To test the
      possibility that baclofen reduced glutamate release onto globus pallidus neurons,
      the effects of baclofen on miniature excitatory postsynaptic currents were
      studied in rat brain slices. Patch-clamp recordings showed that baclofen at 30
      microM significantly reduced the frequency of the miniature excitatory
      postsynaptic currents. However, baclofen induced a weak outward current only in a
      minority of globus pallidus neurons. These pre- and postsynaptic effects of
      baclofen were reversed or prevented by CGP55845A. These results suggest that
      GABA(B) receptor in globus pallidus plays an important role in the regulation of
      movement by modulating glutamatergic inputs at a presynaptic site.

PMID- 12204212
TI  - Abnormal distributions of callosal commissural and corticothalamic neurons in the
      cerebral neocortex of Shaking Rat Kawasaki.
AB  - Shaking Rat Kawasaki (SRK) is an autosomal recessive mutant rat recognized by
      unstable gait and tremor and by early death around the time of weaning. We
      previously reported that corticospinal tract neurons are malpositioned in the
      motor cortex of the SRK rat [Ikeda and Terashima (1997) J. Comp. Neurol. 383, 370
      380]. In the present study, we examined the distribution pattern of callosal
      commissural (CC) and corticothalamic (CT) neurons of SRK and normal rats with the
      injection of horseradish peroxidase (HRP) into the contralateral hemisphere or
      wheat germ agglutinin-conjugated HRP into the ventral lateral thalamic nucleus.
      The intracortical distribution pattern of retrogradely labeled CC and CT neurons
      in the motor cortex of SRK rat was abnormal: CC neurons were more deeply situated
      and CT neurons were more superficially situated in the SRK cortex than the
      corresponding components in the normal cortex. Most of labeled CC and CT neurons
      had abnormal dendritic configurations. Statistical analysis revealed that the
      difference of the mean intracortical position of CC and CT neurons of the SRK was
      significantly different from the normal counterparts (Student's t-test, P<0.01).
      Taken together with previous findings, our data demonstrate that the abnormal
      cytoarchitecture of SRK cortex resembles the reeler cortex.

PMID- 12204213
TI  - Elevated intracellular zinc and altered proton homeostasis in forebrain neurons.
AB  - Using the H(+)-sensitive fluorophore 2',7'-bis-(2-carboxyethyl)-5-(and-6)
      carboxyfluorescein (BCECF) and microfluorimetry, we investigated how elevated
      intracellular free zinc ([Zn(2+)](i)) altered intracellular proton concentration
      (pH(i)) in dissociated cultures of rat forebrain neurons. Neurons exposed to
      extracellular zinc (3 microM) in the presence of the Zn(2+)-selective ionophore
      pyrithione (20 microM) underwent intracellular acidification that was not
      reversed upon washout of the stimulus. Application of a membrane-permeant Zn(2+)
      chelator, but not an impermeant chelator, partially restored pH(i). Removal of
      extracellular Ca(2+) greatly inhibited [Zn(2+)](i)-induced acidification,
      suggesting that acidification was a secondary consequence of Ca(2+) entry.
      Additional experiments suggested that Ca(2+) entered through the plasma membrane
      sodium/calcium exchanger (NCE), because a specific inhibitor of reverse mode NCE
      operation, KB-R7943 (1 microM), significantly inhibited Zn(2+)-induced
      acidification. In addition to the phenomenon of [Zn(2+)](i)-induced
      acidification, we found that elevated [Zn(2+)](i) inhibited neuronal recovery
      from low pH(i). Neurons exposed to a protonophore underwent robust acidification,
      and pH(i) recovery ensued upon protonophore washout. In contrast, neurons
      acidified by the protonophore in the presence of Zn(2+) (3 microM) and pyrithione
      (20 microM) showed no ability to recover from low pH(i). Application of a
      membrane-permeant Zn(2+) chelator partially restored pH(i) to pre-stimulus
      values. Experiments designed to elucidate mechanisms responsible for pH(i)
      regulation revealed that neurons relied primarily on bicarbonate exchange for
      proton export, suggesting that elevated [Zn(2+)](i) might impede pH(i) by
      inhibiting proton efflux via bicarbonate exchange. These results provide novel
      insights into the physiological effects of raising [Zn(2+)](i), and may help
      illuminate the mechanisms by which Zn(2+) injures neurons.

PMID- 12204214
TI  - Differential cortical acetylcholine release in rats performing a sustained
      attention task versus behavioral control tasks that do not explicitly tax
      attention.
AB  - The present study used microdialysis techniques to compare acetylcholine release
      in the frontoparietal cortex of rats performing in a task requiring sustained
      attention with that of rats performing in two control procedures. The two control
      procedures were a fixed-interval 9-s schedule of reinforcement assessing
      primarily the effects of operant responding and comparable reward rates, and an
      operant procedure designed to test the effects of lever extension to prompt
      responding. These two control procedures involved comparable sensory-motor and
      motivational variables to those of the sustained attention task, but did not
      explicitly tax attentional processes. Performance of the sustained attention task
      was associated with a significant increase in cortical acetylcholine efflux,
      reaching a maximum of nearly 140%. Performance of the two control procedures was
      associated with significantly smaller (approximately 50%) increases in cortical
      acetylcholine release. This robust dissociation between attentional and control
      performance-associated increases in cortical acetylcholine release resulted, in
      part, from the elimination of the pre-task transfer of the animals into the
      operant chambers and the associated increases in acetylcholine release observed
      in previous studies. The present results support the hypothesis that demands on
      attentional performance, as opposed to the frequency of lever pressing, reward
      delivery and other task-related variables, selectively activate the basal
      forebrain corticopetal cholinergic system.

PMID- 12204215
TI  - Ultrastructural localization of enkephalin and mu-opioid receptors in the rat
      ventral tegmental area.
AB  - Enkephalins are endogenous ligands for opioid receptors whose activation potently
      modulates the output of mesocorticolimbic dopaminergic neurons within the ventral
      tegmental area. Many of the reinforcing effects of enkephalins in the
      mesocorticolimbic system are mediated by mu-opioid receptors. To determine the
      sites for Leu(5)-enkephalin activation of mu-opioid receptors in the ventral
      tegmental area, we examined the dual electron microscopic immunocytochemical
      localization of their respective antigens in this region of rat brain. Enkephalin
      immunoperoxidase reaction product and mu-opioid receptor immunogold-silver
      labeling showed similar cellular and subcellular distribution in both the
      paranigral and parabrachial subdivisions of the ventral tegmental area.
      Enkephalin immunoreactivity was mainly localized in small unmyelinated axons
      (50.4%) and in axon terminals (40.4%). The majority of these terminals formed
      symmetric, inhibitory-type synapses, many of which were on dendrites expressing
      plasmalemmal mu-opioid receptors. Appositional contacts were also often seen
      between axons or terminals that were differentially labeled for the two antigens.
      In addition, some of the enkephalin-labeled terminals and a few somatodendritic
      profiles showed a plasmalemmal or vesicular localization of mu-opioid receptors.
      Our results indicate that dendritic targets of inhibitory terminals, as well as
      nearby axon terminals, are potential sites for enkephalin activation of mu-opioid
      receptors throughout the ventral tegmental area. Moreover, co-localization of
      enkephalin and mu-opioid receptors in selective neuronal profiles may indicate an
      autoregulatory role for these receptors or their internalization along with the
      bound ligand in this brain region.

PMID- 12204216
TI  - Firing modes of midbrain dopamine cells in the freely moving rat.
AB  - There is a large body of data on the firing properties of dopamine cells in
      anaesthetised rats or rat brain slices. However, the extent to which these data
      relate to more natural conditions is uncertain, as there is little quantitative
      information available on the firing properties of these cells in freely moving
      rats. We examined this by recording from the midbrain dopamine cell fields using
      chronically implanted microwire electrodes. (1) In most cases, slowly firing
      cells with broad action potentials were profoundly inhibited by the dopamine
      agonist apomorphine, consistent with previously accepted criteria. However, a
      small group of cells was found that were difficult to classify because of
      ambiguous combinations of properties. (2) Presumed dopamine cells could be
      divided into low and high bursting (>40% of their spikes in bursts) groups, with
      the majority having low bursting rates. The distribution of burst incidence was
      similar to that previously reported with chloral hydrate anaesthesia, but the
      average intraburst frequency was higher in the conscious animal at rest and was
      higher again in bursts triggered by salient stimuli. (3) There was no evidence
      for spike frequency adaptation within bursts on average, consistent with the
      hypothesis that afterhyperpolarisation currents may be disabled during
      behaviourally induced bursting. (4) Presumed dopamine cells responded to reward
      related stimuli with increased bursting rates and significantly higher intraburst
      frequencies compared to bursts emitted outside task context, indicating that
      modulation of afferent activity might not only trigger bursting, but may also
      regulate burst intensity. (5) In addition to the irregular single spike and
      bursting modes we found that extremely regular (clock-like) firing, previously
      only described for dopamine cells in reduced preparations, can also be expressed
      in the freely moving animal. (6) Cross-correlation analysis of activity recorded
      from simultaneously recorded neurones revealed coordinated activity in a quarter
      of dopamine cell pairs consistent with at least "functional" connectivity. On the
      other hand, most dopamine cell pairs showed no correlation, leaving open the
      possibility of functional sub-groupings within the dopamine cell fields. Taken
      together, the data suggest that the basic firing modes described for dopamine
      cells in reduced or anaesthetised preparations do reflect natural patterns of
      activity for these neurones, but also that the details of this activity are
      dependent upon modulation of afferent inputs by behavioural stimuli.

PMID- 12204217
TI  - Chronic estrogen deficiency leads to molecular aberrations related to
      neurodegenerative changes in follitropin receptor knockout female mice.
AB  - The follitropin receptor knockout (FORKO) mouse undergoes ovarian failure,
      thereby providing an animal model to investigate the consequences of the
      depletion of circulating estrogen in females. The estrogen deficiency causes
      marked defects in the female reproductive system, obesity, and skeletal
      abnormalities. In light of estrogen's known pleiotropic effects in the nervous
      system, our study examined the effects of genetically induced estrogen
      testosterone imbalance on this system in female FORKO mice. Circulating
      concentrations of 17-beta-estradiol (E2) in FORKO mice are significantly
      decreased (FORKO -/-: 1.13+/-0.34 pg/ml; wild-type +/+: 17.6+/-3.5 pg/ml,
      P<0.0001, n=32-41); in contrast, testosterone levels are increased (-/-: 37.7+/
      2.3 pg/ml; wild-type +/+: 3.9+/-1.7 pg/ml, P<0.005, n=25-33). The focus was on
      the activities of key enzymes in the central cholinergic and peripheral nervous
      systems, on dorsal root ganglia (DRGs) capacity for neurite outgrowth, and on the
      phosphorylation state of structural neurofilament (NF) proteins. Choline
      acetyltransferase activity was decreased in several central cholinergic
      structures (striatum 50+/-3%, hippocampus 24+/-2%, cortex 12+/-3%) and in DRGs
      (11+/-6%). Moreover, we observed aberrations in the enzymatic activities of
      mitogen-activated protein kinases (extracellular-regulated kinase and c-Jun N
      terminal kinase) in the hippocampus, DRGs, and sciatic nerves. Hippocampal and
      sensory ganglia samples from FORKO mice contained hyper-phosphorylated NFs.
      Finally, explanted ganglia of FORKO mice displayed decreased neurite outgrowth
      (20-50%) under non-treated conditions and when treated with E2 (10 nM). Our
      results demonstrate that genetic depletion of circulating estrogen leads to
      biochemical and morphological changes in central and peripheral neurons, and
      underlie the importance of estrogen in the normal development and functioning of
      the nervous system. In particular, the findings suggest that an early and
      persisting absence of the steroid leads to neurodegenerative changes and identify
      several key enzymes that may contribute to the process. This model provides a
      system to explore the consequences of circulating estrogen deprivation and other
      hormonal imbalances in the nervous system.

PMID- 12204218
TI  - Regulation of medial prefrontal cortex dopamine by alpha-amino-3-hydroxy-5
      methylisoxazole-4-propionate/kainate receptors.
AB  - In the medial prefrontal cortex, repeated cocaine produces tolerance of the
      extracellular dopamine response to subsequent cocaine injection. These studies
      characterized the influence of alpha-amino-3-hydroxy-5-methylisoxazole-4
      propionate/kainate receptors on the medial prefrontal cortex dopamine response to
      acute cocaine, amphetamine and potassium chloride as a first step to assess
      whether these receptor subtypes may be candidates for mediating dopamine
      tolerance after repeated cocaine. Local infusion of 10 microM 6-cyano-7
      nitroquinoxaline-2,3-dione (CNQX) produced an approximate 40% increase in
      dopamine levels in the medial prefrontal cortex, while a 30 microM dose did not
      alter basal levels infused over a 3-h period. Thus, 30 microM CNQX was chosen for
      the remaining experiments, and was infused for 1 h prior to and during all in
      vivo treatments. Local medial prefrontal cortex infusion of the 30 microM dose
      blocked the small increase in dopamine levels elicited by systemic saline
      injection (maximum of 26%), as well as the much larger increase in response to
      acute cocaine injection (maximum of 340%). Local infusion of D-amphetamine (3 and
      30 microM) through the probe increased dopamine to 300 and 600% of basal levels,
      respectively. Co-infusion of CNQX partially blocked the response for the first 40
      min, but dopamine levels recovered by 60 min later. Local infusion of 100 mM
      potassium chloride elicited a 600% increase in dopamine levels, which was
      attenuated approximately 50% by CNQX co-infusion. Potassium-stimulated release of
      dopamine was also measured in vitro in medial prefrontal cortical and striatal
      tissue. By 30 s after potassium addition, dopamine levels increased to 800% above
      baseline in the medial prefrontal cortex, and this increase was blocked by the
      presence of 30 microM CNQX. In contrast, potassium-stimulated dopamine release in
      striatal tissue was approximately 250% above basal levels, with no effect of CNQX
      on dopamine release. Locomotor behavior collected during dialysis experiments
      demonstrated that increased activity induced by local infusion of potassium
      chloride was severely attenuated by co-infusion of 30 microM CNQX, while no
      effects of this drug were found for cocaine-elicited behavior. These results
      suggest a potent influence of glutamate via alpha-amino-3-hydroxy-5
      methylisoxazole-4-propionate/kainate receptors on extracellular dopamine in the
      medial prefrontal cortex, and these receptors may regulate dopamine release
      through a presynaptic mechanism. The findings may help elucidate the role of
      medial prefrontal cortex dopamine-glutamate interactions in drug abuse and stress
      and drug-precipitated psychosis.

PMID- 12204219
TI  - Stage-specific promoter activity from stably maintained episomes in Plasmodium
      falciparum.
AB  - Genomic DNA is organised at its simplest level within phased arrays of
      nucleosomes, a structure key to the correct transcriptional regulation of the
      encoded genes. Here we studied chromatin formation on DNA transfected into
      Plasmodium falciparum either as an episomal plasmid or following integration by
      homologous recombination. We show that stably maintained and replicated plasmid
      assembles phased arrays of nucleosomes and that a reporter gene is transcribed in
      an appropriate temporal manner. These data provide a key observation for the
      future investigation of promoter structure and function with transfected DNA in
      Plasmodium spp.

PMID- 12204221
TI  - Characterisation of the cysteine protease ER60 in transgenic Schistosoma mansoni
      larvae.
AB  - Proteinases have been found to play important roles in parasites. They are
      involved in developmental processes and facilitate invasion of host tissues as
      well as the digestion of host molecules for nutrition. The cysteine protease ER60
      from Schistosoma mansoni, originally characterised in adults to be expressed in
      excretory organs, was analysed in larval stages. Transcripts were found in
      miracidia, in vitro generated mother sporocysts and cercariae. After cloning the
      promoter and terminator of the ER60 gene, a transformation vector was constructed
      containing the green fluorescent protein reporter gene flanked by the regulatory
      elements. The ER60-green fluorescent protein vector was used for transfection
      experiments of COS-7 cells demonstrating the functionality of the promoter in the
      heterologous system. To analyse the expression pattern of ER60-green fluorescent
      protein in larval S. mansoni, in vitro generated mother sporocysts were
      transformed by particle bombardment, a method which allows gene transfer into
      schistosomes. Molecular analyses demonstrated transcription and translation of
      the transgene. Furthermore, confocal laser scanning microscopy revealed ER60
      induced green fluorescent protein fluorescence within the larvae. Inside primary
      sporocysts, tissue-specific activity was localised in the gland cells,
      protonephridia and several cytons. These results suggest that ER60 is expressed
      in the ES system of larvae and, amongst other functions, may play a role in
      penetration and migration processes.

PMID- 12204220
TI  - Biogenesis of iron-sulphur clusters in amitochondriate and apicomplexan protists.
AB  - During the last 4 years there has been an enormous interest in the question how
      iron-sulphur ([Fe-S]) clusters, which are essential building blocks for life, are
      synthesised and assembled into apo-proteins, both in prokaryotes and in
      eukaryotes. The emerging picture is that the basic mechanism of this pathway has
      been well conserved during evolution. In yeast and probably all other eukaryotes
      the mitochondrion is the place where [Fe-S] clusters are synthesised, even for
      extramitochondrial [Fe-S] cluster-containing proteins, and a number of proteins
      have been functionally characterised to a certain extent within this pathway.
      However, almost nothing is known about this aspect in parasitic protists,
      although recent studies of amitochondriate protists and on the plastid-like
      organelle of apicomplexan parasites, the apicoplast, have started to change this.
      In this article I will summarise the current view of [Fe-S] cluster biogenesis in
      eukaryotes and discuss its implications for amitochondriate protists and for the
      plastid-like organelle of apicomplexan parasites.

PMID- 12204222
TI  - Toxoplasma gondii eukaryotic translation initiation factor 4A associated with
      tachyzoite virulence is down-regulated in the bradyzoite stage.
AB  - Comparative proteome analysis of mouse-virulent and attenuated Toxoplasma gondii
      strain revealed that steady-state synthesis of an unknown 53 kDa protein is
      markedly reduced in attenuated parasites. The results from protein
      microsequencing allowed isolation of a single-copy gene encoding a T. gondii
      homologue of eukaryotic translation initiation factor (eIF)4A. The deduced
      primary structure exhibits all sequence motifs typical of eIF4A. Differential
      expression of eIF4A between virulent and attenuated parasites was reconfirmed by
      immunoblot. Consistent with an involvement in the ribosomal preinitiation
      complex, the protein was localised in the tachyzoite extranuclear cytosol, being
      loosely associated with microsomal particles. Immunofluorescence detection of
      eIF4A in T. gondii stages of the intermediate host indicated that the protein is
      tachyzoite-specific. Stage-dependent expression is regulated at the
      transcriptional level as determined by reverse transcription-polymerase chain
      reaction and immunoblot. The down-regulation of eIF4A in attenuated T. gondii
      parasites and in the bradyzoite stage implies a role in tuning of the homeostasis
      of protein biosynthesis.

PMID- 12204223
TI  - The predictability of helminth community structure in space: a comparison of fish
      populations from adjacent lakes.
AB  - Patterns in helminth community structure can suggest that various processes are
      acting to shape parasite communities into organised, non-random assemblages of
      species. It is not clear, however, whether a pattern observed in one host
      population at one time would be observed again at another time, or at the same
      time in a different but comparable host population. Here, we test the
      repeatability of parasite community structure in space, and to a lesser extent
      time, with data on helminth parasites of two fish species, perch Perca
      fluviatilis and roach Rutilus rutilus, collected in different seasons from four
      adjacent lakes in Central Finland. Since populations of the same fish species
      harbour the same parasite species and were sampled in the same way, we would
      expect similar patterns in the structure of their helminth parasites if the same
      structuring processes are acting in all lakes. We found that no pairwise
      association between the most common helminth species were observed consistently
      between seasons within lakes, or among lakes during the same season. Similarly,
      nested subset patterns of species assembly were observed in some samples, but not
      consistently between seasons or among lakes. The lack of repeatability in space
      and between seasons shown by these analyses indicates that although helminth
      community structure often departs from randomness, it does not do so in a
      consistent and predictable manner. There may be some general, large-scale
      processes acting to structure helminth communities, but local or seasonal
      influences can often either mask their action, or play more important roles
      themselves.

PMID- 12204224
TI  - Evaluating specific adhesion of Plasmodium falciparum-infected erythrocytes to
      immobilised hyaluronic acid with comparison to binding of mammalian cells.
AB  - A feature of infection with Plasmodium falciparum is the ability of parasite
      infected erythrocytes to adhere to vascular endothelial cells and accumulate in
      vital organs, associated with severe clinical disease. Hyaluronic acid was
      recently identified as a receptor for adhesion and has been implicated in
      mediating the accumulation of parasites in the placenta. Here, we report in vitro
      assays to measure specific adhesion of infected erythrocytes to hyaluronic acid
      that is distinct from binding to chondroitin sulphate A, another
      glycosaminoglycan implicated as a receptor in placental malaria. In this study,
      specific adhesion of mature stage infected erythrocytes to hyaluronic acid of
      high purity immobilised on plastic surfaces was abolished by pre-treating
      hyaluronic acid with a specific hyaluronate lyase from Streptomyces, whereas the
      same treatment of chondroitin sulphate A had little effect. Adhesion to
      hyaluronic acid could not be explained by the presence of chondroitin sulphate A
      or other glycosaminoglycans in the hyaluronic acid preparations. Chinese hamster
      ovary cells bound in a similar manner in the assays and confirmed that hyaluronic
      acid was appropriately immobilised for cell adhesion. In contrast to parasites,
      these cells did not adhere to chondroitin sulphate A. The adsorption of
      hyaluronic acid onto plastic surfaces was also confirmed by the use of a specific
      hyaluronic acid-binding protein. Fixing cells with glutaraldehyde at the
      completion of adhesion assays reduced the number of parasites remaining adherent
      to hyaluronic acid, but not to chondroitin sulphate A or CD36. These findings
      have important implications for understanding and evaluating interactions between
      P. falciparum and hyaluronic acid that may be involved in disease pathogenesis.

PMID- 12204225
TI  - Exogenous nitric oxide triggers Neospora caninum tachyzoite-to-bradyzoite stage
      conversion in murine epidermal keratinocyte cell cultures.
AB  - Neospora caninum, like Toxoplasma gondii, undergoes stage conversion in
      chronically infected animals, and forms tissue cysts which contain the slowly
      proliferating bradyzoite stage. These tissue cysts are delineated by a cyst wall,
      protect the parasite from physiological and immunological reactions on part of
      the host, and bradyzoites remain viable within an infected host for many years.
      However, unlike T. gondii, N. caninum bradyzoites have been difficult to obtain
      using in vitro culture techniques, and current protocols, based on those
      developed for T. gondii, have been shown to be not very efficient in promoting
      tachyzoite-to-bradyzoite stage conversion. We report here an alternative in vitro
      culture method to obtain stage conversion of N. caninum from the proliferative to
      the cystic stage by using the Nc-Liverpool isolate, murine epidermal
      keratinocytes as host cells, and continuous treatment of infected cultures with
      70 microM sodium nitroprusside for up to 8 days. This treatment significantly
      reduced parasite proliferation as assessed by Neospora-specific quantitative real
      time PCR. The expression of bradyzoite markers was analysed by immunofluorescence
      following 4 and 8 days of in vitro culture using antibodies directed against
      bradyzoite antigen 1, the mAbCC2, and the lectin Dolichos biflorus agglutinin.
      Expression of the tachyzoite-specific immunodominant antigen NcSAG1 and the
      tachyzoite antigen NcMIC1 was also assessed. Transmission electron microscopy
      revealed that the majority of parasitophorous vacuoles were in the process of
      forming a distinct cyst wall through accumulation of granular material at the
      periphery of the vacuole, and parasites exhibited the typical features of
      bradyzoites. These findings demonstrate the usefulness of this culture technique
      as a promising way to study tachyzoite-to-bradyzoite stage conversion in N.
      caninum in vitro.

PMID- 12204226
TI  - Strain typing in Leishmania donovani by using sequence-confirmed amplified region
      analysis.
AB  - To differentiate strains of Leishmania donovani, allelic markers at the DNA level
      were developed by sequence-confirmed amplified region analysis (SCAR). Homologous
      fragments from different strains of L. donovani were amplified by PCR using
      random primers and subsequently screened for single-strand conformation
      polymorphisms. Direct sequencing revealed 55 sequence polymorphisms in eight co
      dominant DNA markers; 38 of them were single point mutations. Heterozygosity was
      evident for 69% and fixed heterozygosity for 25% of all polymorphisms. At most
      polymorphic sites one of the segregation genotypes was missing. Nineteen unique
      multilocus genotypes were identified among 29 strains of L. donovani. One
      genotype was represented by eight Sudanese strains; also two strains from Sudan
      as well as two strains from Kenya, respectively, shared identical genotypes. All
      other strains had individual multilocus genotypes. Calculation of genetic
      distances showed a correlation between multilocus genotypes and the geographical
      origin of these strains. African strains were found in one well-supported cluster
      with Kenyan and Sudanese strains clearly separated. SCAR markers seem to
      represent a random sample of neutral genetic variation present in natural
      populations. They are co-dominant because they can detect all possible allele
      combinations in a diploid organism and may, therefore, be very useful for
      population genetic analysis in Leishmania.

PMID- 12204227
TI  - IL-4 is required to prevent filarial nematode development in resistant but not
      susceptible strains of mice.
AB  - The murine Litomosoides sigmodontis model of filarial infection provides the
      opportunity to elucidate the immunological mechanisms that determine whether
      these nematode parasites can establish a successful infection or are rejected by
      the mammalian host. BALB/c mice are fully susceptible to L. sigmodontis infection
      and can develop patent infection, with the microfilarial stage circulating in the
      bloodstream. In contrast, mice on the C57BL background are largely resistant to
      the infection and never produce a patent infection. In this study, we used IL-4
      deficient mice on the C57BL/6 background to address the role of IL-4 in the
      development of L. sigmodontis parasites in a resistant host. Two months after
      infection, adult worm recovery and the percentage of microfilaraemic mice in
      infected IL-4 deficient mice were comparable with those of the susceptible BALB/c
      mice while, as expected, healthy adults were not recovered from wild type C57BL/6
      mice. The cytokine and antibody responses reveal that despite similar
      parasitology the two susceptible strains (BALB/c and IL-4 deficient C57BL/6) have
      markedly different immune responses: wild type BALB/c mice exhibit a strong Th2
      immune response and the IL-4 deficient C57BL/6 mice exhibit a Th1 response. We
      also excluded a role for antibodies in resistance through infection of B-cell
      deficient C57BL/6 mice. Our data suggest that the mechanisms that determine
      parasite clearance in a resistant/non-permissive host are Th2 dependent but that
      in a susceptible/permissive host, the parasite can develop in the face of a Th2
      dominated response.

PMID- 12204228
TI  - Molecular and enzymatic characterisation of Schistosoma mansoni thioredoxin.
AB  - Defense against oxidative damage can be mediated through glutathione and/or
      thioredoxin utilising systems. Here, we report the identification and
      characterisation of a thioredoxin from Schistosoma mansoni. The predicted protein
      has similarity to previously characterised thioredoxins including conservation of
      the redox active site. Recombinant six-histidine tagged schistosome thioredoxin
      had insulin reduction activity and supported the enzymatic function of
      thioredoxin reductase and thioredoxin peroxidase. By Western blotting, all
      mammalian stages of the schistosome lifecycle expresses thioredoxin. Thioredoxin
      is present in egg secretory products and antibodies against the recombinant
      protein produce the circumoval precipitin reaction. This is the first
      identification of defined antigen producing this reaction. Furthermore,
      thioredoxin is a novel egg immunogen as it elicits an antibody response in
      schistosome-infected mice. The most significant IgG production against
      thioredoxin occurs after parasite oviposition commences. These observations
      suggest that thioredoxin participates in processes vital to the parasite and may
      facilitate the passage and survival of eggs across inflamed host tissues.

PMID- 12204229
TI  - Characterisation and developmental expression of a chitinase gene in Heterodera
      glycines.
AB  - A chitinase full-length cDNA (designated Hg-chi-1) was isolated from a Heterodera
      glycines oesophageal gland cell-specific long-distance PCR cDNA library. The cDNA
      hybridised to genomic DNA of H. glycines in Southern blots. The Hg-chi-1 cDNA
      contained an open reading frame encoding 350 amino acids with the first 23 amino
      acids being a putative signal peptide for secretion. Hg-CHI-1 contained a
      chitinase 18 family catalytic domain, and chitinolytic activity of recombinant Hg
      CHI-1 was confirmed in glycol-chitin substrate gel electrophoresis. In situ mRNA
      hybridisation analyses showed that transcripts of Hg-chi-1 accumulated
      specifically in the subventral oesophageal gland cells of parasitic stages of H.
      glycines, but Hg-chi-1 expression was not detected in eggs or hatched pre
      parasitic second-stage juveniles, suggesting that this chitinase does not have a
      role in egg hatching of H. glycines. The biological function of Hg-CHI-1 in H.
      glycines remains to be determined.

PMID- 12204230
TI  - Inflammatory responses in the intestinal mucosa of gerbils and hamsters
      experimentally infected with the adult stage of Taenia solium.
AB  - The inflammatory response in gerbils and hamsters harbouring experimental
      infections with Taenia solium adult parasites as well as worm burden and duration
      of infections were examined. For this purpose, non-suppressed or immunosuppressed
      rodents were infected with eight cysticerci and necropsied at different times up
      to 35 days post-infection. Cells in the mucosa surrounding the implantation site
      of T. solium scolices (duodenum-jejunum) and in ileum were counted in stained
      sections. A competitive enzyme linked immunosorbent assay was used to determine
      histamine concentration in intestinal fluid. In non-suppressed hosts, an
      inflammatory reaction developed with scarce macrophages, a slight increase of
      plasma cells, lymphocytes and fibroblasts, a moderate increase of eosinophils and
      neutrophils, and high numbers of goblet and mast cells. Goblet cells began to
      increase at 6 days post-infection and peaked at 13 days post-infection with a
      four-fold increase with respect to the control group. Mast cells only increased
      in gerbils starting at 9 days post-infection with an eight-fold increase when
      cells peaked between 11 and 19 days post-infection. Histamine concentration in
      intestinal fluid of gerbils had a similar behaviour to mast cells. Minimal
      increase of mast cells was seen in hamsters. The recovery of tapeworms was
      inversely related to the number of both cell types, which decreased when
      tapeworms were eliminated. Infections lasted up to 25 days in gerbils and up to
      46 days in hamsters. Worms measured only 1-2 cm in gerbils and up to 40 cm in
      hamsters. When gerbils were suppressed with the steroid methyl predinisolone,
      tapeworms could be recovered up to 35 days post-infection and tapeworms measured
      up to 22 cm, a minor increase of goblet and mast cells was observed and histamine
      concentration was similar to that in non-infected animals. Our results suggest
      that expulsion of T. solium in gerbils and hamsters may be related to the
      increase of goblet cells and mast cells, but these cells may have different roles
      in each rodent model of taeniosis.

PMID- 12204231
TI  - Effect of somatostatin on gastrointestinal contractility in Schistosoma mansoni
      infected mice.
AB  - Schistosoma mansoni infection induces severe gastrointestinal motility
      disturbances which are characterised by hyperactivity of intestinal muscle,
      abdominal pain, diarrhoea, vomiting and nausea. During schistosomiasis, the
      neuropeptide somatostatin is generated within inflammatory granulomas. However,
      somatostatin is also an important inhibitory modulator of gastrointestinal
      motility. In the present study, we have investigated the potential of
      somatostatin to reduce schistosomiasis-induced hyperactivity of gastrointestinal
      smooth muscle. Organ bath experiments were performed to study the contractility
      of isolated smooth muscle strips of intestine from control mice and from mice
      that were infected with S. mansoni for 2, 4, 8 and 16 weeks. Electrical field
      stimulation (0.5-8 Hz) of enteric nerves induced frequency-dependent neurogenic
      contractions of cholinergic origin in all regions of the small intestine.
      Somatostatin (0.1-1 microM) concentration-dependently inhibited the contractions
      to enteric nerve stimulation in the small intestine from uninfected control mice
      and from acutely S. mansoni infected mice (2 and 4 weeks of infection). After 8
      weeks of infection with S. mansoni, this inhibitory effect of somatostatin was
      less pronounced and after 16 weeks of infection it was completely abolished.
      Histology demonstrated that chronic infection of mice with S. mansoni was
      associated with significant alterations in the musculature of the small
      intestine. These alterations may be associated with physiological changes in the
      responsiveness to somatostatin and suggest that the somatostatin neuroregulatory
      circuit of enteric neurotransmission in the small intestine is disturbed during
      chronic schistosomiasis mansoni.

PMID- 12204232
TI  - Appropriate use of parametric methods and analysis in parasitology research.

PMID- 12204233
TI  - Use of a fast EM algorithm for 3D image reconstruction with the YAP-PET
      tomograph.
AB  - OBJECTIVE: We would like to improve the image reconstructions for both signal-to
      noise ratio (SNR) and spatial resolution characteristics for the small animal
      positron emission tomograph YAP-PET, built at the Department of Physics of
      Ferrara University. The three-dimensional (3D) filtered backprojection (FBP)
      algorithm, usually used for image reconstruction, has a limited angle restriction
      due to the tomograph geometry, which causes a serious loss in sensitivity.
      METHODS: We implemented a 3D iterative reconstruction program using the symmetry
      and sparse properties of the 'probability matrix', which correlates the emission
      from each voxel to the detector within a coincidence tube. A fraction only of
      matrix elements are calculated before the reconstruction and stored on disk: this
      allows us to avoid on-line computation. A depth dependent function differentiates
      the voxels in a coincidence tube. Three experimental phantoms with no background
      were reconstructed by using the program, in comparison with traditionally used
      FBP. RESULTS: The adopted method allowed us to reduce the computation time
      significantly. Furthermore, the simple depth dependent function improved the
      spatial resolution. With 64 x 64 x 20 voxels of 0.625 x 0.625 x 2.0 mm(3) in the
      field of view, the computation time was less than 4 min per iteration on a Sparc
      Ultra 450 Workstation, and less than 6 min per iteration on a Mac-PPC G3 300 MHz:
      the spatial resolution measured with a 0.8 mm diameter 18F-FDG filled capillary
      reconstructed in this way was 2.0 mm FWHM. By decreasing the voxel size to 0.3125
      x 0.3125 x 2.0 mm(3) per voxel the transaxial FWHM was 1.7 mm with a computation
      time of 15 min per iteration on a Sparc Ultra 450. By using all the acquired
      data, the SNR improves from 1.3 to 6.0 in the worst measured case, a pair of
      0.8mm diameter 18F-FDG filled capillaries, which are 2.5 mm apart each other.
      CONCLUSION: The adoption of iterative reconstruction allowed us to overcome the
      loss in sensitivity of previously used FBP: this improved the SNR. The studies of
      symmetry and sparse properties avoided a severe increase of the reconstruction
      time and of storing space on disk. This fast EM Algorithm is now routinely used
      for the image reconstruction with the YAP-PET tomograph.

PMID- 12204234
TI  - Texture analysis of lesions in breast ultrasound images.
AB  - We investigate the use of Haralick's texture features and posterior acoustic
      attenuation descriptors (PAAD) for the characterization of ultrasound (US) breast
      lesions. 71 lesions (24 cyst, 21 benign solid mass and 26 malignant solid masses)
      were manually segmented on two-dimensional breast US images. 28 Haralick's
      descriptors and two PAAD were evaluated on these segmented lesions. Mean of Sum
      Average, Range of Sum Entropy and the second PAAD best discriminated cysts from
      noncysts. Range of Correlation and the second PAAD best discriminated solid
      malignant from benign lesions. Computerized analysis of breast US images can
      increase the specificity of breast sonography by providing a better
      characterization of solid lesions.

PMID- 12204235
TI  - Computer aided diagnosis of breast cancer in digitized mammograms.
AB  - A computer aided neural network classification of regions of suspicion (ROS) on
      digitized mammograms is presented in this paper which employs features extracted
      by a new technique based on independent component analysis. Our approach is
      concentrated in finding a set of independent source regions that generate the
      observed mammograms. The coefficients of the linear transformation of the source
      regions are used as features that describe effectively any normal and abnormal
      region in digital mammograms as well as benign and malignant ROS in the latter
      case. Extensive experiments in the MIAS Database have shown a recognition
      accuracy of 88.23% in the detection of all kinds of abnormalities and 79.31% in
      the task of distinguishing between benign and malignant regions, outperforming in
      both cases standard textural features, widely used for cancer detection in
      mammograms.

PMID- 12204236
TI  - CT findings of abdominal tuberculosis in 12 patients.
AB  - Our purpose was to evaluate the Computed Tomography (CT) findings of the
      abdominal tuberculosis (TBC) retrospectively which was diagnosed
      histopatologically. This study included 12 patients. All patients were evaluated
      by abdominal CT study. Most findings of CT studies were mesenteric calcified or
      noncalcified lymphadenopathies, ascites, thickened intestinal wall located on the
      right lower quadrant of abdomen, thickening of peritoneum, mottled soft-tissue
      densities in omentum and mesenterium. In addition, one of the patients had
      bilateral calcified adrenal glands and one of them had calcified mass in adrenal
      gland. If peritoneal thickening, ascites, abdominal lymphadenophaties and
      thickened intestinal walls are obtained, TBC should be considered in differential
      diagnosis in developing countries.

PMID- 12204237
TI  - Diffusion MRI in Rasmussen's encephalitis, herpes simplex encephalitis, and
      bacterial meningoencephalitis.
AB  - Three patients with Rasmussen's encephalitis, herpes simplex type 1 encephalitis,
      and bacterial meningoencephalitis are included in this study. Echo-planar
      diffusion MRI was acquired with the trace protocol at 1.5 T. b= 1000 s/mm(2)
      images, and apparent diffusion coefficient (ADC) maps were studied with respect
      to lesion identification. ADC values were also studied, and compared to those of
      25 normals. In Rasmussen's encephalitis b= 1000 s/mm(2) images were uninformative
      while ADC maps had superior information. In herpes simplex type 1 encephalitis
      both b= 1000 s/mm(2) images, and ADC maps had diagnostic information. In
      meningoencephalitis b= 1000 s/mm(2) images had superior information, especially
      with respect to early cerebritis while ADC maps were negative. In conclusion,
      diffusion MRI provided useful imaging data on different types of encephalitis,
      either on b= 1000 s/mm(2) images or on ADC maps, or on both.

PMID- 12204238
TI  - Callosal changes in obstructive hydrocephalus: observations with FLAIR imaging,
      and diffusion MRI.
AB  - Sagittal and transverse fluid attenuated inversion recovery (FLAIR) images were
      obtained in age-matched 16 normal individuals, and 24 patients with obstructive
      hydrocephalus. The inner (inferior) callosal surface, which is covered by
      ependyma, was electronically measured ranging from 0.15 to 0.25 cm (mean= 0.20+/
      0.02 cm) in normal individuals. This region was thicker in hydrocephalus cases
      due to transcallosal accumulation of water, ranging from 0.29 to 1.10 cm (mean=
      0.65+/-0.30 cm). Furthermore, there was a prominent difference between mild
      hydrocephalus and moderate-to-severe hydrocephalus cases that in mild
      hydrocephalus the ranges were 0.29-0.40 cm (mean= 0.34+/-0.03 cm), and in
      moderate-to-severe hydrocephalus the ranges were 0.50-1.10 cm (mean= 0.80+/-0.22
      cm). It is concluded that especially sagittal FLAIR images could be useful for
      identifying especially milder forms of hydrocephalus by evaluation of the
      appearance and thickness of the inner callosal layer. Twelve patients with
      moderate-to-severe obstructive hydrocephalus, and eight of the controls were
      studied with diffusion MRI, using the echo-planar trace imaging. In moderate-to
      severe hydrocephalus patients apparent diffusion coefficient (ADC) values from
      the inner callosal surface were high, similar to that of transependymal
      resorption of water, ranging from 1.30 to 2.20 x 10 x (-3)mm(2)/s (mean: 1.78+/
      0.27 x 10 x (-3) mm(2)/s), compared to the normal ADC values of the splenium in
      controls: 0.78+/-0.12 x 10 x (-3) mm(2)/s.

PMID- 12204239
TI  - MRI and diffusion MRI in nonparaneoplastic limbic encephalitis.
AB  - This paper reports an 65-year-old woman with nonparaneoplastic limbic
      encephalitis. On MRI and diffusion MRI, diffuse and symmetrical, bilateral high
      signal lesions were evident in the medial temporal lobes. The affected areas were
      hyperintense on b= 1000 s/mm(2) (heavily diffusion-weighted or true diffusion)
      images, a pattern similar to cytotoxic edema. However, apparent diffusion
      coefficient (ADC) values read directly from corresponding ADC maps at each
      temporal lobe were within normal limits: 0.96 and 0.97 x 10 x (-3) mm(2)/s,
      respectively, excluding cytotoxic edema. The changes were shown to be resolved on
      a 9-month follow-up MRI.

PMID- 12204240
TI  - Tumefactive demyelinating lesions by combined perfusion-weighted and diffusion
      weighted imaging.
AB  - Tumefactive demyelinating lesion may sometimes mimic intracranial neoplasm or
      abscess and pose a diagnostic problem both clinically and radiologically. The
      diagnosis is even more complicated since multiple sclerosis is relatively
      uncommon among Chinese and due to low incidence of oligoclonal protein in the
      cerebrospinal fluid. We present a Chinese lady with tumefactive demyelinating
      lesion, which mimic cystic neoplasm and cerebral abscess. The use of perfusion
      and diffusion weighted imaging obviated unnecessary surgical biopsy.

PMID- 12204241
TI  - Evaluation of cerebral abscesses by diffusion-weighted MR imaging and MR
      spectroscopy.
AB  - Cerebral abscess may sometimes mimic necrotic tumor and cystic metastases both
      clinically and radiologically. The imaging findings may be indistinguishable on
      conventional magnetic resonance imaging. Although recent studies have shown that
      cerebral abscess displays restricted diffusion on diffusion-weighted imaging
      (DWI), it is not pathognomic. Necrotic tumor and cystic metastases may
      occasionally have restricted diffusion on DWI. Since the urgency of surgical
      intervention and approach of surgery is different, MR Spectroscopy may be used in
      conjunction with DWI in establishing the correct diagnosis.

PMID- 12204242
TI  - An unusual arterial supply of the kidney from the opposite renal artery.
AB  - We describe an extremely rare case with a supplementary artery arising from an
      opposite renal artery without renal anomalies in position and in form. An unusual
      artery crossing the aorta can be suggested by contrast-enhanced computed
      tomography. A renal cell carcinoma is supplied by the branch of the opposite
      renal artery.

PMID- 12204243
TI  - Hydatid cyst: a rare cause of ascites.
AB  - A 26 year old woman with ascites was admitted for further investigations. A
      diagnosis of hydatid cyst disease was suggested on the basis of a combination of
      abdominal ultrasonography, computerised tomography and latex agglutination tests.
      This diagnosis was confirmed following surgical intervention. Hydatid cyst
      disease is a rare cause of ascites and we review the etiology and clinical
      features of this condition.

PMID- 12204246
TI  - The Drosophila hugin gene codes for myostimulatory and ecdysis-modifying
      neuropeptides.
AB  - In a genomic screen we isolated the Drosophila gene hugin (hug, cytology 87C1-2)
      by cross-hybridisation to a human glial cell line-derived neurotrophic factor
      cDNA. Upon cDNA sequence analysis and in vitro expression assays, the hugin gene
      was found to encode a signal peptide containing proprotein that was further
      processed in Schneider-2 cells into peptides similar to known neuropeptides. Two
      of the peptides were similar to FXPRL-amides (pyrokinins) and to the ecdysis
      triggering hormone, respectively. The former displayed myostimulatory activity in
      a bioassay on the cockroach hyperneural muscle preparation, as well as in the
      Drosophila heart muscle assay. Hugin is expressed during the later half of
      embryogenesis and during larval stages in a subgroup of neurosecretory cells of
      the suboesophageal ganglion. Ubiquitous ectopic hugin expression resulted in
      larval death predominantly at or shortly after ecdysis from second to third
      instar, suggesting that at least one of the posttranslational cleavage products
      affects molting of the larva by interfering with the regulation of ecdysis.

PMID- 12204247
TI  - Epigenetic reprogramming in mouse primordial germ cells.
AB  - Genome-wide epigenetic reprogramming in mammalian germ cells, zygote and early
      embryos, plays a crucial role in regulating genome functions at critical stages
      of development. We show here that mouse primordial germ cells (PGCs) exhibit
      dynamic changes in epigenetic modifications between days 10.5 and 12.5 post
      coitum (dpc). First, contrary to previous suggestions, we show that PGCs do
      indeed acquire genome-wide de novo methylation during early development and
      migration into the genital ridge. However, following their entry into the genital
      ridge, there is rapid erasure of DNA methylation of regions within imprinted and
      non-imprinted loci. For most genes, the erasure commences simultaneously in PGCs
      in both male and female embryos, which is completed within 1 day of development.
      Based on the kinetics of this process, we suggest that this is an active
      demethylation process initiated upon the entry of PGCs into the gonadal anlagen.
      The timing of reprogramming in PGCs is crucial since it ensures that germ cells
      of both sexes acquire an equivalent epigenetic state prior to the differentiation
      of the definitive male and female germ cells in which new parental imprints are
      established subsequently. Some repetitive elements, however, show incomplete
      erasure, which may be essential for chromosome stability and for preventing
      activation of transposons to reduce the risk of germline mutations. Aberrant
      epigenetic reprogramming in the germ line would cause the inheritance of
      epimutations that may have consequences for human diseases as suggested by
      studies on mouse models.

PMID- 12204248
TI  - SAGE identification of differentiation responsive genes in P19 embryonic cells
      induced to form cardiomyocytes in vitro.
AB  - Transcriptome profiling facilitates the identification of developmentally
      regulated genes. To quantify the functionally active genome of P19 embryonic
      carcinoma (EC) cells induced to form cardiomyocytes, we employed serial analysis
      of gene expression (SAGE) to sequence and compare a total of 171,735 SAGE tags
      from three libraries (undifferentiated P19 EC cells, differentiation days 3 + 0.5
      and 3 + 3.0). After in vitro differentiation, only 3.1% of the gene products
      demonstrated significant (P < 0.05) changes in expression. The most highly
      significant changes (P < 0.01) involved altered expression of 410 genes encoding
      predominantly transcription factors, differentiation factors and growth
      regulators. Quantitative polymerase chain reaction analysis and in situ
      hybridization revealed five growth regulators (Dlk1, Igfbp5, Hmga2, Podxl and
      Ptn) and two unknown ESTs with expression profiles similar to known cardiac
      transcription factors, implicating these growth regulators in cardiac
      differentiation. These SAGE libraries thus serve as a reference resource for
      understanding the role of differentiation-dependent genes in embryonic stem cell
      models induced to form cardiomyocytes in vitro.

PMID- 12204249
TI  - Multiple functions of LIM domain-binding CLIM/NLI/Ldb cofactors during zebrafish
      development.
AB  - The crucial involvement of CLIM/NLI/Ldb cofactors for the exertion of the
      biological activity of LIM homeodomain transcription factors (LIM-HD) has been
      demonstrated. In this paper we show that CLIM cofactors are widely expressed
      during zebrafish development with high protein levels in specific neuronal cell
      types where LIM-HD proteins of the Isl class are synthesized. The overexpression
      of a dominant-negative CLIM molecule (DN-CLIM) that contains the LIM interaction
      domain (LID) during early developmental stages of zebrafish embryos results in an
      impairment of eye and midbrain-hindbrain boundary (MHB) development and
      disturbances in the formation of the anterior midline. On a cellular level we
      show that the outgrowth of peripheral but not central axons from Rohon Beard (RB)
      and trigeminal sensory neurons is inhibited by DN-CLIM overexpression. We
      demonstrate a further critical role of CLIM cofactors for axonal outgrowth of
      motor neurons. Additionally, DN-CLIM overexpression causes an increase of Isl
      protein expression levels in specific neuronal cell types, likely due to a
      protection of the DN-CLIM/LIM-HD complex from proteasomal degradation. Our
      results demonstrate multiple roles of the CLIM cofactor family for the
      development of entire organs, axonal outgrowth of specific neurons and protein
      expression levels.

PMID- 12204250
TI  - Tramtrack co-operates to prevent inappropriate neural development in Drosophila.
AB  - Each sensory organ of the Drosophila peripheral nervous system is derived from a
      single sensory organ precursor cell (SOP). These originate in territories defined
      by expression of the proneural genes of the Achaete-Scute complex (AS-C).
      Formation of ectopic sensilla outside these regions is prevented by
      transcriptional repression of proneural genes. We demonstrate that the BTB/POZ
      domain transcriptional repressor Tramtrack (Ttk) co-operates in this repression.
      Ttk is expressed ubiquitously, except in proneural clusters and SOPs. Ttk over
      expression represses proneural genes and sensilla formation. Loss of Ttk enhances
      bristle-promoting mutants. Using neural repression as an assay, we dissected
      functional domains of Ttk, confirming the importance of the bric-a-brac-tramtrack
      broad complex (BTB) motif. We show that the Ttk BTB domain is a protein-protein
      interaction motif mediating tetramer formation.

PMID- 12204251
TI  - A screen for co-factors of Six3.
AB  - The vertebrate Six3 gene a homeobox gene of the Six-family, plays a crucial role
      in early eye and forebrain development. Here we report the isolation of candidate
      factors that interact with Six3 in a yeast two-hybrid screen. Among these are two
      basic helix loop helix (bHLH) domain containing proteins. Biochemical analysis
      reveals that the bHLH proteins ATH5, ATH3, NEUROD as well as ASH1 interact
      specifically with XSix3. By defining the interacting domains we show that the
      bHLH domain of NEUROD interacts with the SIX domain of XSix3. The co-expression
      of the interacting molecules during late retina determination/differentiation
      suggests a new role for Six3 and the respective interaction partner also in these
      late steps of eye development.

PMID- 12204252
TI  - Normal fate and altered function of the cardiac neural crest cell lineage in
      retinoic acid receptor mutant embryos.
AB  - Mouse embryos lacking the retinoic acid (RA) receptors RARalpha1 and RARbeta
      suffer from a failure to properly septate (divide) the early outflow tract of the
      heart into distinct aortic and pulmonary channels, a phenotype termed persistent
      truncus arteriosus. This phenotype is associated with a failure in the
      development of the cardiac neural crest cell lineage, which normally forms the
      aorticopulmonary septum. In this study, we examined the fate of the neural crest
      lineage in RARalpha1/RARbeta mutant embryos by crossing with the Wnt1-cre and
      conditional R26R alleles, which together constitute a genetic lineage marker for
      the neural crest. We find that the number, migration, and terminal fate of the
      cardiac neural crest is normal in mutant embryos; however, the specific function
      of these cells in forming the aorticopulmonary septum is impaired. We furthermore
      show that the neural crest cells themselves do not utilize retinoid receptors and
      do not respond to RA during this process, but rather that the phenotype is cell
      non-autonomous for the neural crest cell lineage. This suggests that an
      alternative tissue in the vicinity of the outflow tract of the heart responds
      directly to RA, and thereby induces or permits the neural crest cell lineage to
      initiate aorticopulmonary septation.

PMID- 12204253
TI  - BrdU-, neuroD (nrd)- and Hu-studies reveal unusual non-ventricular neurogenesis
      in the postembryonic zebrafish forebrain.
AB  - In the postembryonic zebrafish forebrain, subpial locations of neurogenesis do
      exist in the early cerebellar external granular layer, and--unusually among
      vertebrates--in the primordial pretectal (M1) and preglomerular (M2) Anlagen as
      shown here with 5-bromo-2'-deoxyuridine (BrdU)/Hu-immunocytochemistry and in situ
      hybridization of neuroD. An intermediate BrdU incubation time of 12-16 h reveals
      in addition to proliferative ventricularly located cells those in M1 and M2. This
      BrdU saturation-labeling shows--in conjunction with a Hu-assay demonstrating
      earliest neuronal differentiation--that proliferating cells in M1 and M2
      represent neuronal progenitors. This is demonstrated by single BrdU-labeled and
      double BrdU-/Hu-labeled cells in these aggregates. Further, expression of NeuroD-
      a marker for freshly determined neuronal cells--confirms this unusual subpial
      postembryonic forebrain neurogenesis.

PMID- 12204254
TI  - Persistent neurogenesis in the teleost retina: evidence for regulation by the
      growth-hormone/insulin-like growth factor-I axis.
AB  - Based on results from previous studies (J. Comp. Neurol. 394 (1998) 386, 395), it
      was hypothesized that the persistent neurogenesis in the retina of teleost fish
      is modulated by insulin-like growth factor-I (IGF-I), which, in turn, is
      regulated by growth hormone (GH). Two approaches were undertaken to test this
      hypothesis. First, a variety of techniques were used to determine if IGF-I and
      the IGF-I receptor (IGF-IR) are expressed in the retina. Second, GH was injected
      into animals to stimulate IGF-I synthesis in target tissues, and IGF-I expression
      and cell proliferation in the retina was quantitatively assayed. Reverse
      transcriptase-polymerase chain reaction, screening a retinal cDNA library and
      Northern analysis showed that genes encoding IGF-I and IGF-IR are expressed in
      the retina of goldfish. In situ hybridization showed that IGF-IR is expressed by
      retinal progenitors and all differentiated retinal neurons. Intraperitoneal
      injections of GH elevate IGF-I mRNA levels in the liver, brain and retina and
      produce a dose-dependent change in the proliferation of stem cells and
      progenitors in the retina. These data indicate that the principal components of
      the IGF-I signaling cascade are present in the retinas of teleosts, and we
      suggest these elements mediate the persistent, growth-associated neurogenesis in
      this tissue.

PMID- 12204255
TI  - Inducible RNA interference uncovers the Drosophila protein Bx42 as an essential
      nuclear cofactor involved in Notch signal transduction.
AB  - We used the UAS/GAL4 two component system to induce mRNA interference (mRNAi)
      during Drosophila development. In the adult eye the expression from white
      transgenes or the resident white locus is significantly repressed by the
      induction of UAS-wRNAi using different GAL4 expressing strains. By induced RNAi
      we demonstrate that the conserved nuclear protein Bx42 is essential for the
      development of many tissues. Phenotypically the effects of Bx42 RNAi resemble
      those obtained for certain classes of Notch mutants, pointing to an involvement
      of Bx42 in the Notch signal transduction pathway. The wing phenotype following
      overexpression of Suppressor of Hairless is strongly enhanced by simultaneous
      Bx42 RNAi induction in the same tissue. Target genes of Notch signaling like cut
      and Enhancer of split m8 were suppressed by induction of Bx42 RNAi. Our results
      demonstrate that inducible RNAi is a powerful tool to study the role of essential
      genes throughout development.

PMID- 12204256
TI  - Defining pallial and subpallial divisions in the developing Xenopus forebrain.
AB  - To shed light on the organisation of the Xenopus laevis telencephalon, we have
      used two sets of developmental regulators: genes acting in early regional
      specification (x-Dll3, x-Nkx2.1, x-Emx1, x-Pax6, x-Eomes) or in cell
      determination (x-Lhx5 and x-Lhx7). After expression patterns analysis, separately
      or combined, on whole-mount brains and serial sections, we identify the Xenopus
      pallium and subpallium, and the subdivisions herein. The data show a conservation
      of the same basic Bauplan for Xenopus forebrain patterning compared to other
      vertebrates, and suggest the possibility for LIM-homeodomain genes to be
      candidate downstream target of the regionalization genes. Comparing the relative
      sizes of the deduced subdivisions, Xenopus seems to have an intermediate
      phylogenetic position in terms of pallium contribution to the telencephalon, and
      ventral pallium contribution to the pallium.

PMID- 12204257
TI  - XPOX2-peroxidase expression and the XLURP-1 promoter reveal the site of embryonic
      myeloid cell development in Xenopus.
AB  - Phagocytic myeloid cells provide the principle line of immune defence during
      early embryogenesis in lower vertebrates. They may also have important functions
      during normal embryo morphogenesis, not least through the phagocytic clearance of
      cell corpses arising from apoptosis. We have identified two cDNAs that provide
      sensitive molecular markers of embryonic leukocytes in the early Xenopus embryo.
      These encode a peroxidase (XPOX2) and a Ly-6/uPAR-related protein (XLURP-1). We
      show that myeloid progenitors can first be detected at an antero-ventral site in
      early tailbud stage embryos (a region previously termed the anterior ventral
      blood island) and transiently express the haematopoetic transcription factors SCL
      and AML. Phagocytes migrate from this site along consistent routes and
      proliferate, becoming widely distributed throughout the tadpole long before the
      circulatory system is established. This migration can be followed in living
      embryos using a 5 kb portion of the XLURP-1 promoter to drive expression of EGFP
      specifically in the myeloid cells. Interestingly, whilst much of this migration
      occurs by movement of individual cells between embryonic germ layers, the rostral
      most myeloid cells apparently migrate in an anterior direction along the ventral
      midline within the mesodermal layer itself. The transient presence of such cells
      as a strip bisecting the cardiac mesoderm immediately prior to heart tube
      formation suggests that embryonic myeloid cells may play a role in early cardiac
      morphogenesis.

PMID- 12204258
TI  - Expression analysis of a novel p75(NTR) signaling protein, which regulates cell
      cycle progression and apoptosis.
AB  - Neurotrophin receptor-interacting MAGE (NRAGE) is the most recently identified
      p75 neurotrophin receptor (p75(NTR)) intracellular binding protein. Previously,
      NRAGE over-expression was shown to mediate cell cycle arrest and facilitate nerve
      growth factor (NGF) dependent apoptosis of sympathetic neuroblasts in a p75(NTR)
      specific manner. Here we have examined the temporal and spatial expression
      patterns of NRAGE over the course of murine embryogenesis to determine whether
      NRAGE's expression is consistent with its proposed functions. We demonstrate that
      NRAGE mRNA and protein are expressed throughout embryonic and adult tissues. The
      mRNA is constitutively expressed within each tissue across development. However,
      expression of NRAGE protein displays a tight temporal tissue specific regulation.
      During early CNS development, NRAGE protein is expressed throughout the neural
      tube, but by later stages of neurogenesis, NRAGE protein is restricted within the
      ventricular zone, subplate and cortical plate. Moreover, NRAGE protein expression
      is limited to proliferative neural subpopulations as we fail to detect NRAGE
      expression co-localized with mature/differentiation associated neuronal markers.
      Interestingly, NRAGE's expression is not restricted solely to areas of p75(NTR)
      expression suggesting that NRAGE may mediate proliferation and/or apoptosis from
      other environmental signals in addition to NGF within the CNS. Our data support
      previously characterized roles for NRAGE as a mediator of precursor apoptosis and
      a repressor of cell cycle progression in neural development.

PMID- 12204259
TI  - Regulated expression of the MADS-box transcription factor SrfA mediates
      activation of gene expression by protein kinase A during Dictyostelium
      sporulation.
AB  - Cell differentiation and morphogenesis are tightly regulated during sporulation
      in the lower eukaryote Dictyostelium discoideum. The control of the cyclic
      adenosine monophosphate (cAMP)-dependent protein kinase (PKA) is essential to
      coordinate these processes. Several signal transduction pathways are being
      recognized that lead to the regulation of intracellular cAMP levels. However,
      very little is known about the events lying downstream of PKA that are essential
      to activate late gene expression and terminal differentiation of the spores. We
      have studied the relationship between PKA and the MADS-box transcription factor
      SrfA, essential for spore differentiation. Constitutive activation of PKA was not
      able to rescue sporulation in a strain that lacks srfA suggesting the possibility
      that srfA functions downstream of PKA in a signal transduction pathway leading to
      spore maturation. A distal promoter region regulates the induction of srfA
      expression in the prespore region during culmination. We found that this promoter
      can be induced precociously by activating PKA with 8-Br-cAMP suggesting a
      transcriptional regulation by PKA. Moreover, precocious sporulation and
      expression of the spore marker spiA in a strain that overexpresses PKA,
      correlates with a precocious induction of srfA expression. The temporal and
      spatial pattern of expression was also studied in a mutant strain lacking the
      main adenylyl cyclase that functions during culmination, ACR. This strain is
      expected to have lower PKA activity and consistently, the level of srfA
      expression was reduced. Moreover, the temporal induction of srfA in the prespore
      region was also delayed during culmination. Our results strongly suggest that PKA
      activation during culmination leads to the induction of the expression of srfA.
      The correct temporal and spatial pattern of srfA expression appears to be part of
      a mechanism that ensures the adequate coordination of gene expression and
      morphogenesis.

PMID- 12204260
TI  - Structure and expression patterns of Drosophila TULP and TUSP, members of the
      tubby-like gene family.
AB  - Tubby is a mouse gene that may provide a model for adult-onset obesity in humans.
      It is a member of a four gene family in mammals that collectively encode the
      Tubby-like proteins (TULPs), putative transcription factors which share similar
      260 amino acid 'tubby domains' at their C-termini. The mammalian genome also
      encodes distant relatives of TULPs, which have been called TUSPs (tubby domain
      superfamily proteins). We have characterized the transcription unit of the single
      Drosophila TULP homolog, analyzed the expression pattern of the Drosophila TULP
      and TUSP genes, and determined the evolutionary relationships between the
      Drosophila proteins and members of the tubby domain superfamily in other
      organisms. Interestingly, like its mammalian homologs, Drosophila TULP is
      principally expressed in the embryonic central and peripheral nervous systems.
      This suggests that mammalian and Drosophila TULPs may possess some conserved
      functional properties in the nervous system. The Drosophila TUSP gene is also
      expressed in the central nervous system and olfactory organ but in few other
      peripheral sensory organs.

PMID- 12204261
TI  - Transcription factors Nkx3.1 and Nkx3.2 (Bapx1) play an overlapping role in
      sclerotomal development of the mouse.
AB  - The homeobox containing transcription factors Nkx3.1 and Nkx3.2 (Bapx1) are
      transiently coexpressed in somites during early embryonic mouse development.
      Targeted disruption of the Nkx3.2 (Bapx1) gene in mice results in limited defects
      of chondrocranial bones and the axial skeleton, particularly pronounced in
      cervical vertebrae. In contrast, inactivation of the Nkx3.1 gene causes no
      apparent skeletal phenotype despite its early expression in sclerotomal cells.
      These observations suggested that both genes might fulfill partially overlapping
      functions during development of the vertebral column. To test this hypothesis we
      have generated Nkx3.1/Nkx3.2 double homozygous mutants. The simultaneous loss of
      both genes caused embryonic lethality between E12.5 and E17.5. Double mutants
      exhibited enhanced defects of vertebrae compared with Bapx1-deficient animals. In
      vertebral anlagen sclerotomal cells condensing around the notochord were almost
      completely lost during early embryogenesis of double null mutants. Defects
      appeared most severe in the cranial region and less prominent in thoracic and
      lumbar regions. The reduction of chondrogenic cells resulted in the incomplete
      formation of vertebral bodies, missing major parts of their ventro-medial
      aspects. The enhanced skeletal phenotype of double null mutants compared to the
      single Bapx1 mutation demonstrates that Nkx3.1 contributes to the formation of
      the axial skeleton in addition to the Bapx1 gene. Moreover, both genes seem to
      collaborate in a yet unknown vital function in the mouse embryo.

PMID- 12204262
TI  - Bristles induce bracts via the EGFR pathway on Drosophila legs.
AB  - A long-standing mystery in Drosophila has been: how do certain bristles induce
      adjacent cells to make bracts (a type of thick hair) on their proximal side? The
      apparent answer, based on loss- and gain-of-function studies, is that they emit a
      signal that neighbors then transduce via the epidermal growth factor receptor
      pathway. Suppressing this pathway removes bracts, while hyperactivating it evokes
      bracts indiscriminately on distal leg segments. Misexpression of the diffusible
      ligand Spitz (but not its membrane-bound precursor) elicits extra bracts at
      normal sites. What remains unclear is how a secreted signal can have effects in
      one specific direction.

PMID- 12204263
TI  - Inducible control of tissue-specific transgene expression in Xenopus tropicalis
      transgenic lines.
AB  - Analysis of gene function in vertebrates is facilitated by gain-of-function
      studies, such as injection of synthetic mRNA in amphibian embryos. This approach
      is hampered by lack of spatial and temporal control of expression of the
      introduced gene product. An additional level of control is obtained by nuclear
      transfer-mediated transgenesis, but functional analyses are complicated by
      variability and background abnormalities in primary transgenic embryos. The
      GAL4/UAS system permits establishment of stable lines and elimination of nuclear
      transfer-associated abnormalities, through generation of separate UAS-'effector'
      and GAL4 'transactivator' transgenic lines. When the GAL4 DNA-binding domain is
      combined with a steroid hormone ligand-binding domain, this system allows full
      temporal regulation of transgene expression by introduction of an exogenous
      steroid analogue, the progesterone antagonist RU486. We show here that by
      crossing stable Xenopus tropicalis transgenic lines, one bearing a UAS-enhanced
      cyan fluorescent protein (ECFP) reporter construct, and the other with a GAL4
      progesterone receptor fusion driven by a retina-specific promoter, reporter
      expression in the resulting embryos can be induced with RU486 in a tissue
      specific manner. These results suggest that the inducible binary system, in which
      the target gene expression can be controlled in a stage- and tissue-specific
      pattern, should be readily applicable for gene function studies at all stages of
      development.

PMID- 12204264
TI  - Molecular cloning and developmental expression of Tlx (Hox11) genes in zebrafish
      (Danio rerio).
AB  - Tlx (Hox11) genes are orphan homeobox genes that play critical roles in the
      regulation of early developmental processes in vertebrates. Here, we report the
      identification and expression patterns of three members of the zebrafish Tlx
      family. These genes share similar, but not identical, expression patterns with
      other vertebrate Tlx-1 and Tlx-3 genes. Tlx-1 is expressed early in the
      developing hindbrain and pharyngeal arches, and later in the putative splenic
      primordium. However, unlike its orthologues, zebrafish Tlx-1 is not expressed in
      the cranial sensory ganglia or spinal cord. Two homologues of Tlx-3 were
      identified: Tlx-3a and Tlx-3b, which are both expressed in discrete regions of
      the developing nervous system, including the cranial sensory ganglia and Rohon
      Beard neurons. However, only Tlx-3a is expressed in the statoacoustic cranial
      ganglia, enteric neurons and non-neural tissues such as the fin bud and
      pharyngeal arches and Tlx-3b is only expressed in the dorsal root ganglia.

PMID- 12204265
TI  - Linker histone H1M transcripts mark the developing germ line in zebrafish.
AB  - Maternally synthesised factors contribute to the establishment of the germ cell
      lineage in lower vertebrates. In zebrafish, germ-soma segregation appears to be
      completed by the late blastula stage of development. To search for new germ cell
      factors in the zebrafish, we have used subtractive cDNA cloning. Here we report
      that linker histone H1M transcripts mark the germ line from the early
      gastrulation up to 18 h post-fertilisation.

PMID- 12204266
TI  - Expression of a linker histone-like gene in the primordial germ cells in
      zebrafish.
AB  - Similar to many other organisms, specification of primordial germ cells (PGCs) in
      zebrafish occurs during early development and depends on inheritance of 'germ
      plasm' determinants. Following their specification, the PGCs exhibit
      characteristic transcriptional profile and cell behaviour. Here we describe the
      cloning, expression pattern and sub-cellular localization of the zebrafish H1
      type linker histone, H1M, which is specifically expressed in the PGCs in the
      second phase of their development. H1M transcripts are uniformly distributed
      during blastula stages, but become restricted to the PGCs during gastrulation and
      remain visible in PGCs as they migrate towards the region of the gonad.

PMID- 12204267
TI  - Ohx is a homeobox-encoding gene preferentially expressed in mature oocytes.
AB  - There is abundant evidence to indicate that the homeobox genes are
      developmentally important. We used the NCBI dbEST databases of early mouse
      embryos to identify novel homeobox-containing sequence tags. Ohx (oocyte-specific
      homeobox gene) was one of several genes identified by in silico cloning. The full
      length Ohx cDNA was cloned and its genomic organization was characterized. The
      Ohx gene spans 1.6 kb, encodes three exons and maps to the proximal region of
      mouse chromosome 7. Reverse transcriptase polymerase chain reaction analyses show
      that Ohx is preferentially expressed in one- and two-cell embryonic stages, as
      well as in the ovary. Whole mount in situ hybridization analysis demonstrates
      that the Ohx mRNA was exclusively localized to the oocytes of the mature ovary.
      Ohx is one of the few homeobox-encoding genes preferentially expressed during
      mammalian oogenesis.

PMID- 12204268
TI  - The Drosophila zinc finger transcription factor CF2 is a myogenic marker
      downstream of MEF2 during muscle development.
AB  - The Drosophila C(2)-H(2)-type zinc-finger transcription factor CF2 has been shown
      to regulate follicular cell fate determination during oogenesis. Here we show
      that CF2 is also expressed in the developing muscles of the embryo where it first
      appears at stage 12 at the time of skeletal myoblast fusion. Later it is
      expressed in all muscle lineages including skeletal, visceral and cardiac.
      Epistatic analysis showed that CF2 expression is dependent on the myogenic factor
      MEF2.

PMID- 12204269
TI  - Expression and splice variant analysis of the zebrafish tcf4 transcription
      factor.
AB  - Wnt signalling has been implicated in antero-posterior patterning of the
      vertebrate embryonic body axis and in a number of other developmental processes.
      One of the downstream effectors of Wnt signalling is the beta-catenin protein
      which complexes with members of the Lef/tcf transcription factor family. In the
      zebrafish, specification of the head has been shown to be dependent on the Tcf3
      protein which acts as a repressor of the posteriorizing activity of Wnt (Nature
      407 (2000) 913). Here, we report the cloning and expression pattern of the
      zebrafish tcf4 gene. In embryos, we find that the tcf4 gene is highly regulated
      at the level of RNA splicing such that the variant proteins that are produced
      contain or lack domains proposed to be essential in repression or activation of
      transcription. Expression of tcf4 mRNA is first detected in a graded fashion in
      the anterior brain and subsequently becomes restricted to the dorsal diencephalon
      and anterior midbrain. There is also transient expression in the anterior
      rhombomeres of the hindbrain and in the developing gut.

PMID- 12204270
TI  - SpADAM, a sea urchin ADAM, has conserved structure and expression.
AB  - ADAMs are multidomain cell surface proteins that function in receptor-ligand
      processing, cell adhesion and fusion, and signaling. SpADAM, a single copy sea
      urchin ADAM gene with a 3072 bp open reading frame, is expressed during embryonic
      and larval development. The deduced SpADAM protein is 1023 amino acids long and
      includes all domains characteristic of ADAMs. Northern blots reveal the presence
      of 4.4 and 2.3 kb SpADAM transcripts throughout development. Predominant SpADAM
      proteins are 131 and 95 kDa. The deduced primary structure of SpADAM is closely
      related to vertebrate ADAMs 12, 13, and 19. SpADAM is expressed during cleavage
      on blastomere surfaces, and later by vegetal plate cells, migrating secondary
      mesenchyme, skeletogenic mesenchyme, muscles, and neurons within the ciliated
      band. Apparently, the structure and types of cells in which ADAM 12/13/19
      orthologues are expressed are conserved in deuterostomes.

PMID- 12204271
TI  - Sequence and expression of FoxB2 (XFD-5) and FoxI1c (XFD-10) in Xenopus
      embryogenesis.
AB  - We report on the temporal and spatial expression pattern of two novel genes of
      the Xenopus fork head/winged helix family, xFoxB2 and xFoxI1c. xFoxB2 is
      activated at the late blastula stage and first expressed within the dorsolateral
      ectoderm except for the organiser territory. During gastrulation, xFoxB2 is found
      in two ectodermal stripes adjacent to the dorsal midline. Expression is
      completely down-regulated during neurulation. However, two distinct sets of cells
      expressing xFoxB2 re-appear in the rhombencephalon of swimming tadpoles. xFoxI1c
      is initially expressed at the early neurula stage in an epidermal ring around the
      neural field. Subsequent expression is found to be increased, and is exclusively
      localised to placodal precursor cells. The placodal expression remains until
      stage 40, when it is restricted to a distinct region in the lateral body wall
      behind the gills.

PMID- 12204272
TI  - Cloning and developmental expression analysis of ltd-1, the Caenorhabditis
      elegans homologue of the mouse kyphoscoliosis (ky) gene.
AB  - We have characterized the developmental expression pattern of the Caenorhabditis
      elegans homologue of the mouse ky gene. The Ky protein has a putative key
      function in muscle development and has homologues in invertebrates, fungi and a
      cyanobacterium. The C. elegans Ky homologue gene has been named ltd-1 for LIM and
      transglutaminase domains gene. The LTD-1::GFP construct is expressed in
      developing hypodermal cells from the twofold stage embryo through adulthood.
      These data define the ltd-1 gene as a novel marker for C. elegans epithelial cell
      development.

PMID- 12204273
TI  - Expression of the AMBP gene transcript and its two protein products, alpha(1)
      microglobulin and bikunin, in mouse embryogenesis.
AB  - The expression pattern of the alpha(1)-microglobulin/bikunin precursor (AMBP)
      gene, and its two protein products were studied in mouse embryos of 8.5-15.5 days
      of embryonic development by in situ hybridization and immunohistochemistry. AMBP
      mRNA is strongly transcribed in liver parenchyma, pancreas, and intestine
      epithelium. Sites of weaker expression are the vessels of the umbilical cord, the
      developing vertebral bodies, and kidney. The alpha(1)-microglobulin and bikunin
      proteins are accordingly present in developing hepatocytes, pancreas, kidney, and
      gut. However, additional sites of protein distribution were found that do not
      correlate to mRNA localization: alpha(1)-microglobulin was found in myocytes and
      bikunin in cardiac muscle, nervous system microvasculature, and connective
      tissue. Both proteins were found in brain mesenchyme and meninges. Thus, a
      restricted expression of the AMBP mRNA in a few organs contrasts to a widespread
      and unique distribution of each of the two proteins.

PMID- 12204274
TI  - Development of the pancreas in medaka.
AB  - In the present work, pancreatic organogenesis has been studied in the medaka
      (Oryzias latipes), a teleost fish with several advantages as an experimental
      system in developmental biology. We demonstrated that the pancreas develops from
      three primordia budding from the dorsal and ventral faces of the gut epithelium.
      Such buds then fuse to form a single endocrine islet surrounded by exocrine
      tissue. Interestingly, the endocrine tissue forms only from the dorsal bud. We
      next analyzed a collection of medakas that had been hybridized with cDNAs derived
      from an anterior brain library. We found new clones expressed in the pancreatic
      region demonstrating that the medaka can be used to define new genes expressed in
      the pancreatic region that follow a specific spatial and temporal pattern of
      expression.

PMID- 12204275
TI  - The dynamic expression pattern of B lymphocyte induced maturation protein-1
      (Blimp-1) during mouse embryonic development.
AB  - We have analyzed the spatial and temporal patterns of B lymphocyte-induced
      maturation protein-1 (Blimp-1) expression during mouse embryonic development.
      Blimp-1 expression is induced early in the anterior definitive endoderm, mesoderm
      of head process, and prechordal plate. In ectoderm-derived tissues at later
      stages, Blimp-1 expression is found in the primitive photoreceptors of neural
      retina, in differentiated epithelial cells of epidermis, tongue, oral and nasal
      cavities, and in the precursors of internal root sheaths of hair follicles. In
      mesoderm-derived tissues, Blimp-1 expression is observed in splanchnopleure, a
      subset of somatopleure-derived cells in limb buds, and myotomes of somites. Blimp
      1 is also expressed in mesenchyme of developing hand plates, digits, branchial
      arches, nasal processes, and external genitalia. Blimp-1 is present in mesenchyme
      derived chondroblasts, supporting cells of taste buds, and papilla of teeth, hair
      follicles and taste buds. In endoderm-derived tissues, Blimp-1 expression in the
      foregut region is restricted to a subset of epithelial cells at the headfold
      stage while expression in the endodermal epithelium of midgut and hindgut
      persists from the headfold stage to birth. Finally, Blimp-1 is expressed in the
      migrating primordial germ cells.

PMID- 12204276
TI  - Expression profiles of the essential intermediate filament (IF) protein A2 and
      the IF protein C2 in the nematode Caenorhabditis elegans.
AB  - The multigene family of intermediate filament (IF) proteins in Caenorhabditis
      elegans covers 11 members of which four (A1-3, B1) are essential for development.
      Suppression of a fifth gene (C2) results in a dumpy phenotype. Expression
      patterns of three essential genes (A1, A3, B1) were already reported. To begin to
      analyze the two remaining RNAi phenotypes we followed the expression of the A2
      and C2 proteins. Expression of A2 mRNA starts in larval stage L1 and continues in
      the adult. Transgenic A2 promoter/gfp larvae strongly display GFP in the main
      body hypodermis but not in seam cells. This pattern and the muscle
      displacement/paralysis induced by RNAi silencing are consistent with the role of
      this protein in keeping the correct hypodermis/muscle relationship during
      development. IF protein C2 occurs in the cytoplasm and desmosomes of intestinal
      cells and in pharynx desmosomes. Expression of C2 starts in the late embryo and
      persists in all further stages.

PMID- 12204277
TI  - Expression of Bblhx3, a LIM-homeobox gene, in the development of amphioxus
      Branchiostoma belcheri tsingtauense.
AB  - Amphioxus Bblhx3 was identified as a LIM-homeobox gene expressed in gastrulae.
      Structural analysis suggested that it is a member of lhx3 but not of lhx1 gene
      group. Whole mount in situ hybridization revealed that expression of Bblhx3 was
      initiated at the early gastrula stage and continued at least until 10-day larvae.
      Expression of Bblhx3 first appeared in the vegetal and future dorsal area in
      initial gastrulae and became restricted to the endoderm during gastrulation. In
      neurulae and early larvae, Bblhx3 was expressed in the developing neural tube,
      the notochord and preoral pit lineage. In 10-day larvae, Bblhx3 was expressed
      only in the preoral pit. This expression pattern is apparently distinct from that
      of vertebrate lhx3 genes that are not expressed during gastrulation.

PMID- 12204278
TI  - Cloning and expression analysis of the chick ortholog of TBX22, the gene mutated
      in X-linked cleft palate and ankyloglossia.
AB  - T-box genes constitute a conserved gene family with important roles in many
      developmental processes. Several family members have been implicated in human
      congenital diseases. Recently, mutations in TBX22 were found to cause X-linked
      cleft palate (CPX and ankyloglossia), a semidominant X-linked disorder affecting
      formation of the secondary palate. Here, we have cloned the chick ortholog of
      human TBX22 and have analyzed its expression during embryogenesis. Expression is
      very prominent in the somites and in the myotome, and in the mandible and maxilla
      of the developing jaw. Other sites of expression include the limbs, the cranial
      mesenchyme and the eye. Hence, Tbx22 expression domains encompass the regions
      important for the development of the disease phenotype.

PMID- 12204279
TI  - The expression of SpRunt during sea urchin embryogenesis.
AB  - The runt box (runx) is a highly conserved DNA binding and protein-protein
      interaction domain that defines a family of heterodimeric transcription factors
      that regulate development in metazoans. The three mammalian runx genes are
      oncogenes with essential functions in normal development: Runx1 is required for
      hematopoiesis and is frequently mutated in human and murine leukemias; Runx2 is
      required for bone development and is associated with human cleidocranial
      dysplasia and murine leukemias; and Runx3 (the evolutionarily basal member of the
      mammalian family) regulates growth of the gut and functions as a tumor suppressor
      in the gastric epithelium (Westendorf and Hiebert, 1999; Li et al., 2002). The
      sea urchin Strongylocentrotus purpuratus contains a single runx gene, SpRunt. We
      present here the initial structural characterization of SpRunt, and its pattern
      of expression during embryogenesis. SpRunt contains two introns, the locations of
      which are identical to those of the second and third introns from promoter P2 of
      the mammalian runx genes. A approximately 6 kb transcript begins to accumulate
      during cleavage. At mesenchyme blastula stage, SpRunt transcripts are found
      throughout the embryo, but specifically enriched in the vegetal plate,
      skeletogenic mesenchyme, and part of the ectoderm. By late gastrula stage
      expression is localized to the endomesoderm and oral ectoderm. In the pluteus
      larva SpRunt transcripts remain confined to the endomesoderm and oral ectoderm,
      with highest levels of accumulation in the foregut and in the ciliary band. These
      data suggest that SpRunt expression is enhanced in proliferating cells.

PMID- 12204280
TI  - Expression of the myogenic regulatory factor Mrf4 precedes or is contemporaneous
      with that of Myf5 in the somitic bud.
AB  - The development of skeletal muscle in vertebrate embryos is controlled by a
      transcriptional cascade involving the four myogenic regulatory factors. In the
      somites of the mouse embryo the order of expression is thought to be Myf5,
      Myogenin, Mrf4 and MyoD. We have re-examined the expression pattern of Mrf4 and
      show that in the hypaxial domain of thoracic somites (the somitic bud) Mrf4
      expression precedes or is contemporaneous with that of Myf5, suggesting that this
      transcription factor plays a hitherto unsuspected role in myogenesis.

PMID- 12204281
TI  - Cloning and expression of Xenopus Lrp5 and Lrp6 genes.
AB  - LRP5 and LRP6 comprise a subfamily of lipoprotein-receptor related proteins that
      function as co-receptors for Wnt proteins. Mutation of human LRP5 is responsible
      for osteoporosis-pseudoglioma syndrome and disruption of Lrp6 in mice causes
      similar effects to mutation of several different Wnt genes. We have cloned
      Xenopus homologues of Lrp5 and Lrp6 (Xlrp5, Xlrp6) and examined their expression
      during embryogenesis. Both genes are expressed maternally and ubiquitously
      through early development. At later stages, Xlrp5 is found in the eye, forebrain,
      hindbrain, branchial arches and the tip of the tail bud. Xlrp6 is expressed
      throughout the central nervous system, branchial arches, in the eye and otic
      vesicle. Both genes are also expressed at the intersomitic boundary. These
      results suggest roles for Wnt signaling via LRP proteins in these tissues.

PMID- 12204283
TI  - Hole is a novel gene product expressed in the developing heart and brain.
AB  - Hole is a novel gene product isolated from a chick heart subtractive
      hybridization. Hole is a six-transmembrane protein (predicted size 311 and 317
      amino acids in chick and mouse) expressed in the cardiac crescent and later in
      the myocardium of the developing chick heart, as well as in the fusing neural
      tube and ganglia. Mouse hole is not expressed in the developing heart, although
      it does share neural expression seen in the chick.

PMID- 12204282
TI  - Cloning and expression of Drosophila SOCS36E and its potential regulation by the
      JAK/STAT pathway.
AB  - The suppressor of cytokine signalling (SOCS) gene family was originally
      identified as an immediate early response to cytokine signalling and function as
      negative regulators of the Janus kinase (JAK)/signal tranducers and activators of
      transcription (STAT) signal transduction pathway [Krebs and Hilton, J. Cell Sci.
      113 (2000) 2813; Starr and Hilton, Int. J. Biochem. Cell Biol. 30 (1998) 1081].
      Although key components of the Drosophila JAK/STAT pathway have been identified
      [Brown et al., Curr. Biol. 11 (2001) 1700, reviewed in Zeidler et al., Oncogene
      19 (2000) 2598], regulators of the pathway, and SOCS genes in particular, have
      not yet been characterised. Here we report the cloning of Drosophila SOCS36E and
      show its expression pattern during embryonic and imaginal disc development.
      SOCS36E is expressed in an essentially identical pattern to the Drosophila
      JAK/STAT pathway ligand unpaired (Upd). It is not expressed in upd mutant embryos
      and is upregulated in response to ectopic activation of the pathway during both
      embryonic and imaginal development.

PMID- 12204284
TI  - Expression pattern of alkaline phosphatase in Dictyostelium.
AB  - We used two different methods to study the expression pattern of alkaline
      phosphatase (alp) in Dictyostelium. In situ staining of the endogenous enzyme
      activity at different stages of development showed that the enzyme was active
      early in the aggregation stage and localized to the area where the tip of the
      first finger was initiated. The activity was localized to the anterior region of
      developing slugs, then became restricted to the region between the prestalk and
      prespore cells at the culmination stage. In the complete fruiting body, the
      activity was confined to the lower and upper cup. A second method to study alp
      expression utilized a beta-galactosidase reporter gene under the control of the
      alp promoter. A low level of beta-galactosidase activity was observed in
      vegetative cells, then increased during development. Reporter gene activity was
      restricted to PstO cells at the slug stage. At the culmination stage, the
      expression was restricted to prestalk cells at the interface between the prestalk
      and prespore cells. In the completed fruiting body, the expression was observed
      in the upper and lower cup.

PMID- 12204285
TI  - A neuropeptide FF-related gene is expressed selectively in neurons of the
      terminal nerve in Danio rerio.
AB  - RFamides constitute a large family of neuromodulatory peptides. We have cloned a
      zebrafish gene, which is presumably a homologue to the mammalian PQRF subfamily
      of RFamides, and named it zfPQRF for its species and subfamily allocation. We
      report that in contrast to its mammalian counterparts zfPQRF is expressed in the
      olfactory bulb and the nucleus olfactoretinalis in the telencephalon, but absent
      in more caudal regions, including hypothalamus, brain stem and spinal cord.
      zfPQRF-expressing neurons originate in the vicinity of the olfactory placode and
      populate the nuclei of the terminal nerve during later development, as
      demonstrated by co-expression of zebrafish salmon-type gonadotropin releasing
      hormone, which was found to exclusively label terminal nerve neurons.

PMID- 12204286
TI  - Krit1/cerebral cavernous malformation 1 mRNA is preferentially expressed in
      neurons and epithelial cells in embryo and adult.
AB  - Cavernous malformations are capillaro-venous lesions mostly located within the
      central nervous system (CCM/OMIM#116860) and occasionally within the skin and/or
      retina. They occur as a sporadic or hereditary condition. Three CCM loci have
      been mapped, and the sole gene identified so far, CCM1, has been shown to encode
      KRIT1, a protein of unknown function. In an attempt to get some insight on the
      relationship between KRIT1 mutations and CCM lesions, we investigated Krit1 mRNA
      expression during mouse development from E7.5 to E20.5 and in adult tissues, of
      both mouse and human origin. A ubiquitous Krit1 mRNA expression was detected from
      E7.5 up to E9.5. Then, it became progressively restricted from E10.5 to E12.5, to
      become detectable later essentially in the nervous system and various epithelia.
      Strong labelling was observed in neurons in the brain, cerebellum, spinal cord,
      retina and dorsal root ganglia. In epithelia, Krit1 mRNA expression was detected
      in differentiating epidermal, digestive, respiratory, uterine and urinary
      epithelia. A similar pattern of expression persisted in mouse and man adult
      nervous system and epithelia. Unexpectedly, in vascular tissues, expression of
      Krit1 was detected only in large blood vessels of the embryo.

PMID- 12204287
TI  - Nurit, a novel leucine-zipper protein, expressed uniquely in the spermatid flower
      like structure.
AB  - Spermatozoa formation involves drastic morphological and cellular
      reconstructions. However, the molecular mechanisms driving this process remain
      elusive. We describe the cloning of a novel murine spermatid-specific gene,
      designated nurit, identified in a two-hybrid screen for proteins that binds the
      Nek1 kinase. Nurit protein harbors a leucine-zipper motif, and two additional
      coiled-coil regions. The C-terminal coiled-coil domain mediates homodimerization
      of the protein. Nurit homologues are found in primates, pig and rodents. nurit is
      transcribed through the elongation stage of the spermatids, but is absent from
      mature spermatozoa. Interestingly, immunogold electron microscopy revealed that
      the protein is restricted, from its first detectable appearance, to a unique
      spermatid organelle called the 'flower-like structure'. The function of this
      structure is unknown, though it may be involved in transporting proteins
      designated to be discarded via the residual bodies. Nurit is the first marker of
      the flower-like structure, and its study may provide an excellent opportunity to
      dissect the function of this organelle.

PMID- 12204288
TI  - Lipid rafts at postsynaptic sites: distribution, function and linkage to
      postsynaptic density.
AB  - Accumulating evidence suggests that special lipid microdomains in the lipid
      membrane play various roles in cellular functions. Neurons also have such
      microdomains, non-caveolar lipid rafts. However, the rafts at the synaptic sites
      had not been reported until 2001, when a raft-like fraction was purified from
      synaptic plasma membrane of the rat forebrain (Mol. Brain Res. 89 (2001) 20).
      This article reviews recent findings on lipid rafts, especially those in the
      brain, and discusses the possible interaction between the postsynaptic raft and
      the postsynaptic density, both of which are essential for the structure and
      function of the postsynaptic side of the synapse.

PMID- 12204289
TI  - Genetics of epilepsy: current status and perspectives.
AB  - Epilepsy affects more than 0.5% of the world's population and has a large genetic
      component. The most common human genetic epilepsies display a complex pattern of
      inheritance and the susceptibility genes are largely unknown. However, major
      advances have recently been made in our understanding of the genetic basis of
      monogenic inherited epilepsies. Progress has been particularly evident in
      familial idiopathic epilepsies and in many inherited symptomatic epilepsies, with
      the discovery that mutations in ion channel subunits are implicated, and direct
      molecular diagnosis of some phenotypes of epilepsy is now possible. This article
      reviews recent progress made in molecular genetics of epilepsy, focusing mostly
      on idiopathic epilepsy, and some types of myoclonus epilepsies. Mutations in the
      neuronal nicotinic acetylcholine receptor alpha4 and beta2 subunit genes have
      been detected in families with autosomal dominant nocturnal frontal lobe
      epilepsy, and those of two K(+) channel genes were identified to be responsible
      for underlying genetic abnormalities of benign familial neonatal convulsions. The
      voltage-gated Na(+) -channel (alpha1,2 and beta1 subunit), and GABA receptor
      (gamma2 subunit) may be involved in the pathogenesis of generalized epilepsy with
      febrile seizure plus and severe myoclonic epilepsy in infancy. Mutations of
      Ca(2+)-channel can cause some forms of juvenile myoclonic epilepsy and idiopathic
      generalized epilepsy. Based upon these findings, pathogenesis of epilepsy as a
      channelopathy and perspectives of molecular study of epilepsy are discussed.

PMID- 12204290
TI  - Effect of isolation on classical conditioned histamine release in guinea pigs.
AB  - To investigate the effect of abrupt or non-abrupt isolation stress on the
      classical conditioned histamine release, socially isolated or paired guinea pigs
      underwent conditioning procedures in which ovalbumin (OA) as an unconditioned
      stimulus (US) and dimethylsulfide (sulfur smelling) as a conditioned stimulus
      (CS) were simultaneously inhaled, and the plasma histamine levels after the
      exposure to the CS in a state of isolation or pairing were measured. The plasma
      histamine levels significantly increased from baseline in response to the CS (P <
      0.05), except in the animals which were abruptly isolated during the exposure to
      the CS. The guinea pigs which were isolated during either the conditioning
      procedures or the exposure to the CS displayed significantly lower levels of
      plasma histamine than did the paired animals during both periods (P < 0.01,
      respectively). The plasma histamine levels in the guinea pigs which were isolated
      or paired during both periods were significantly higher than those of the control
      animals which had received the CS and the US separately (P < 0.05 and P < 0.01).
      A change of social relations, particularly isolation during the presentation of
      the CS, may have a suppressive effect on immediate asthmatic responses due to the
      conditioning mechanism.

PMID- 12204291
TI  - Modulation of noradrenergic and serotonergic transmission by noxious stimuli and
      intrathecal morphine differs in the dorsal raphe nucleus of anesthetized rat: in
      vivo voltammetric studies.
AB  - We examined the effects of cutaneous noxious heat as well as the intrathecal
      administration of morphine on the oxidation current of peaks 1 and 2 in the
      dorsal raphe nucleus (DRN) of anesthetized rats. Differential normal pulse
      voltammetry with carbon fiber electrodes identified distinct oxidation currents
      at +120 mV (peak 1: catechol signals) and +280 mV (peak 2: 5-hydroxyindole
      signals). The catechol signal was significantly increased by 22.9 +/- 4.2% after
      applying cutaneous noxious heat at 52 degrees C. The 5-hydroxyindole signal was
      decreased by 39.8 +/- 4.3 and by 25.2 +/- 4.7% after stimulation with cutaneous
      noxious heat at 52 and 45 degrees C, respectively. A low dose of morphine (2.5
      microg) potentiated the increase in the catechol signal and the decrease in the 5
      hydroxyindole signal induced by noxious heat, and a high dose (10.0 microg)
      attenuated both. The effects of morphine at low (2.5 microg) and high doses (10.0
      microg) were antagonized by naloxone (0.5 mg/kg, i.p.). These results indicate
      that noxious heat stimulation increased the catechol signal and decreased the 5
      hydroxyindole signal in the DRN. The intrathecal administration of morphine
      affects the noxious stimulation-induced activity of noradrenergic and
      serotonergic neurotransmission in the DRN.

PMID- 12204292
TI  - Transcriptional responses of the rat vasopressin gene to acute and repeated acute
      osmotic stress.
AB  - To determine the impact of hypertonic saline administration upon rat arginine
      vasopressin (AVP) gene transcription in supraoptic nucleus neurons, a probe
      complementary to the first intron (AVP1) of AVP was used to measure changes in
      AVP heteronuclear RNA (hnRNA) levels. Animals that received hypertonic saline had
      increases in AVP1 after 15 and 30 min, with a return to baseline levels by 180
      min. In a double injection paradigm, animals were given an injection of normal or
      hypertonic saline followed 180 min later by a second injection of normal or
      hypertonic saline and sacrificed 30 min later. When both injections were
      hypertonic saline (H-H), AVP1 levels were greater than levels seen after a single
      hypertonic saline injection, or after an injection of normal saline followed by a
      second injection of hypertonic saline (N-H). This study shows acute, repeated
      exposure to hypertonic saline causes a robust increase in vasopressin gene
      transcription. Since a second hyperosmotic stimulus is known to increase neuronal
      firing rate and activity, our results suggest that a correlation exists with
      intracellular mechanisms regulating vasopressin gene transcription.

PMID- 12204293
TI  - Brain-specific endothelial induction of prostaglandin E(2) synthesis enzymes and
      its temporal relation to fever.
AB  - Brain endothelial cells are hypothesized to be the major source of prostaglandin
      E(2) (PGE(2)) responsible for fever because they express 2 PGE(2)-synthesizing
      enzymes (cyclooxygenase-2 and microsomal-type PGE synthase) in response to
      pyrogens. To further validate this hypothesis, we examined in rats whether
      endothelial expression of these enzymes occurs only in the brain, and whether the
      time course of enzyme expression in brain endothelial cells can explain the time
      courses of brain PGE(2) level and fever. Intraperitoneal injection of
      lipopolysaccharide induced these enzymes only in brain endothelial cells, but not
      in those of peripheral organs including the neck, heart, lung, liver and kidney.
      Induction of these enzymes in brain endothelial cells was first noticed at 1.5 h
      after lipopolysaccharide injection, at which time elevation of PGE(2) was also
      first detected. Fever started just after this time point. These results
      demonstrate the significance of brain endothelial cells in the PGE(2) production
      during fever. Unexpectedly, PGE(2) level markedly dropped at 5 h in spite of high
      levels of these enzymes, implicating the existence of an unknown mechanism that
      suppresses PGE(2) level during the recovery phase of fever.

PMID- 12204294
TI  - Role of cerebral dopamine but not plasma insulin, leptin and glucocorticoid in
      the development of tolerance to the anorectic effect of amphetamine.
AB  - Repeated treatment with amphetamine (AMPH), an anorectic agent, induced a marked
      anorexia on day 1 followed by a gradual reversion of this anorexia to the normal
      level of feeding (tolerant anorexia). The mechanism for this tolerant anorexia
      remained unknown because it might be related with multiple parameters, such as
      the change of cerebral dopamine (DA) or the plasma levels of insulin, leptin and
      glucocorticoid. Results revealed that plasma insulin and leptin concentrations
      remained unchanged during repeated AMPH administration, revealing that these two
      factors are not involved. Also, glucocorticoids were not required for the
      development of tolerant anorexia, as this effect could not be prevented by
      adrenalectomy. However, AMPH-induced anorexia was decreased by the pretreatment
      of alpha-methyl-p-tyrosine, an inhibitor of central catecholamine synthesis, and
      was increased by the pretreatment of nomifensine, a blocker of DA transporter
      that increased extracellular DA content in brain, revealing that the change of DA
      content could modify the action of tolerant anorexia. It is suggested that the
      decrease of inhibitory action of DA in brain during repeated AMPH plays a
      functional role in the development of tolerance to the anorectic response of
      AMPH.

PMID- 12204295
TI  - The expression of neurokinin-1 receptor at striatal and pallidal levels in normal
      human brain.
AB  - To further our knowledge of the site of action of substance P (SP) in the human
      basal ganglia, we applied single- and double-antigen localization methods to
      human postmortem tissue to compare the distribution of SP and its high affinity
      receptor neurokinin-1 (NK1R) at striatal and pallidal levels. The human striatum
      was found to harbor numerous heterogeneously distributed aspiny neurons that
      expressed NK1R. Most of them were of small size, but a moderate number of large
      sized neurons and a small number of medium-sized neurons also expressed NK1R. The
      medium-sized NK1R-positive neurons coexpressed parvalbumin and appear to
      represent a hitherto unknown striatal interneuron. The three types of striatal
      NK1R-positive neurons were preferentially localized in the peripheral region of
      the striosomes, which were identified by their intense immunostaining for the
      limbic system-associated membrane protein. Numerous NK1R expressing neurons also
      occurred in both external (GPe) and internal (GPi) segments of the globus
      pallidus, as well as in the ventral pallidum (GPv). There was a marked decreasing
      rostrocaudal gradient in the number of these neurons in the GPe, but not in the
      GPi. A multitude of smooth and highly branched SP-immunoreactive fibers pervaded
      the entire pallidal complex and some of these fibers were in close contact with
      NK1R-positive neurons in the GPi, as well as in the rostral portion of the GPe.
      The latter result reveals that the so-called 'direct' striatofugal pathway
      provides SP-immunoreactive collaterals to the GPe, a finding that is at odd with
      the current model of basal ganglia organization.

PMID- 12204297
TI  - Reciprocal connections of the hippocampal area CA1, the lateral nucleus of the
      amygdala and cortical areas in a combined horizontal slice preparation.
AB  - The entorhinal and perirhinal cortices, the hippocampus and the amygdala are
      heavily interconnected limbic structures that are implicated in memory, and under
      pathological conditions, in seizure generation and propagation of temporal lobe
      epilepsy. In-vitro coronal preparations have been limited by the anatomical
      disposition of these structures. Here we describe a modified horizontal slice
      preparation that includes all these structures in the same plane. To evaluate
      whether axonal connectivities are preserved, fluorescent tracers were used. Most
      of the connections known from in-vivo studies within and between the entorhinal
      and perirhinal cortices, the amygdala (basolateral nucleus, lateral nucleus, and
      amygdalopiriform transition area) and the hippocampus were preserved in the 400
      microm-thick horizontal slices employed.

PMID- 12204296
TI  - Regional differences of the temporal EEG dynamics during the first 30 min of
      human sleep.
AB  - The analysis of the time-course of different EEG bands during the first sleep
      cycle has up to now taken into account mostly central derivations. In the present
      study, we assessed the topographical differences of the time-course of different
      EEG bands during the first 30 min of sleep, by analysing the EEG power from four
      different scalp locations along the antero-posterior axis. Correlation of EEG
      bands time courses within and between each derivation has also been evaluated.
      Delta-theta (1-6.75 Hz) and alpha (7-10.75 Hz) activities exhibited an antero
      posterior gradient with maximal power on the frontal lead and increased at all
      derivations in the first 15 min and 5 min periods, respectively. Then alpha power
      decreased at all derivations, but the frontal. Sigma EEG power (11-15.75 Hz)
      showed a coherent behavior over the four derivations, characterized by a steep
      increase in the first 3-5 min of sleep, followed by a stable decreasing trend.
      Beta power (16-25.75 Hz) linearly decreased only on the more posterior
      derivations, abruptly increasing on the frontal lead after a 15 min interval.
      Correlations between delta-theta and alpha band were higher on the frontal
      derivation. Moreover, frontal alpha was strongly related to delta-theta activity
      on all the four derivations, while occipital alpha was not. The negative
      correlations between delta-theta and beta time courses were very high on all
      derivations but the frontal one. This study shows the existence of topographical
      differences in the time-course of different EEG bands during the first 30 min of
      sleep. The peculiar behavior of the alpha and beta EEG bands over the frontal
      derivation indicates the need to re-consider the functional role of traditional
      EEG bands during sleep.

PMID- 12204298
TI  - Synaptic mechanisms of inspiratory off-switching evoked by pontine pneumotaxic
      stimulation in cats.
AB  - To elucidate synaptic mechanisms and the involvement of N-methyl-D-aspartate
      (NMDA) receptors in inspiratory off-switching (IOS) evoked by the stimulation of
      the nucleus parabrachialis medialis (NPBM), excitatory and inhibitory
      postsynaptic potentials (EPSPs and IPSPs) were recorded from bulbar augmenting
      inspiratory (aug-I) and postinspiratory (PI) neurons in vagotomized cats.
      Stimulation of NPBM produced either transient inhibition or premature termination
      of inspiration (reversible or irreversible IOS), depending on the stimulus
      intensity. Each neuron displayed four-phasic postsynaptic responses during the
      reversible IOS, i.e. Phase 1 EPSPs, Phase 2 IPSPs, Phase 3 EPSPs and Phase 4
      IPSPs in aug-I neurons, and Phase 1 plus 2 EPSPs, Phase 3 IPSPs and Phase 4 EPSPs
      in PI neurons. During the irreversible IOS, Phase 4 responses were replaced by
      sustained hyperpolarization in aug-I neurons and decrementing depolarization in
      PI neurons. Blockade of NMDA receptors by dizocilpine (0.3 mg kg(-1) i.v.)
      selectively increased Phase 4 potentials in both types of neurons and decreased
      the thresholds for evoking the irreversible IOS. The NPBM-induced responses had a
      pattern and time-course similar to those induced by vagal stimulation. The
      present results suggest that pneumotaxic and vagal inputs converge on the common
      IOS circuit, and the effectiveness of both inputs is modulated by NMDA receptors.

PMID- 12204299
TI  - Two broad-specificity dipeptide hydrolysing activities from cytoplasm of guinea
      pig brain, both of which contain prolinase but neither of which contain
      carnosinase activity.
AB  - Two dipeptide hydrolysing activities were purified from cytoplasm of guinea pig
      brain. Dipeptide hydrolase I has been shown to be a strict dipeptidase requiring
      a free amino and a free carboxy terminus, while dipeptide hydrolase II displays
      very low activity against Leu-Leu-Leu. Of the 41 dipeptides presented to both
      enzymes, 25 were hydrolysed by both enzymes, while six (including carnosine) were
      hydrolysed by neither. Six were hydrolysed solely by dipeptide hydrolase I and
      four were hydrolysed solely by Pro-Leu hydrolase II. Kinetic analysis suggested
      that dipeptides which were hydrolysed with unfavourable kinetics or which were
      not hydrolysed by one dipeptide hydrolase were generally hydrolysed with more
      favourable kinetics by the other dipeptide hydrolase. Dipeptide hydrolase I
      displays optimum activity at pH 9.0, while dipeptide hydrolase II was optimally
      active at pH 8.0. Both enzymes were inhibited by 1,10-phenanthroline, p
      chloromercuribenzoate and bestatin. Dipeptide hydrolase II was more strongly
      inhibited by arphamenine B than was dipeptide hydrolase I. Dipeptide hydrolase II
      was also inhibited by N-ethyl maleimide, while dipeptide hydrolase I was
      inhibited by dithiothreitol. Native M(r) values of 70,000 and 67,000 were
      computed for dipeptide hydrolase I and dipeptide hydrolase II, respectively.
      Sodium dodecyl sulphate polyacrylamide gel electrophoresis conducted with each
      enzyme under denaturing conditions suggested that both enzymes were comprised of
      a single polypeptide chain.

PMID- 12204302
TI  - Deterministic and stochastic features of fMRI data: implications for analysis of
      event-related experiments.
AB  - As the limits of stimuli presentation rates are explored in event-related fMRI
      design, there is a greater need to assess the implications of averaging raw fMRI
      data. Selective averaging assumes that the fMRI signal consists of task-dependent
      signal, random noise, and non-task dependent brain signal that can be modeled as
      random noise so that it tends to zero when averaged over a practical number of
      trials. We recorded a total of four fMRI data series from two normal subjects
      (subject 1, axially acquired; subject 2, coronally acquired) performing a simple
      visual event-related task and a water phantom with the same fMRI scanner imaging
      parameters. To determine which fraction of the fMRI data was deterministic as
      opposed to random, we created different data subsets by taking the odd or even
      time points of the full data sets. All data sets were first dimension-reduced
      with principal component analysis (PCA) and separated into 100 spatially
      independent components with independent component analysis (ICA). The mutual
      information between best-matching pairs of components selected from full data set
      subset comparisons was plotted for each data set. Visual inspection suggested
      that 45-85 components were reproducible, and hence deterministic, accounting for
      79-97% of the variance, respectively, in the raw data. The reproducible
      components exhibited much less trial-to-trial variability than the raw data from
      even the most activated voxel. Many (22-47) of reproducible components were
      significantly affected by stimulus presentation (P < 0.001). The most
      significantly-stimulus-correlated component was strongly time-locked to stimulus
      presentation and was directly stimulus correlated, corresponding to occipital
      brain regions. However, other spatially distinct task-related components
      demonstrated variable temporal relationships with the most significantly-stimulus
      correlated component. Our results suggest that the majority of the variance in
      fMRI data is in fact deterministic, and support the notion that the data consist
      of differing components with differing temporal relationships to visual
      stimulation. They further suggest roles for restricting interpretations of the
      spatial extent of activation from event-related designs to a specific region of
      interest (ROI) and/or first separating the data into spatially independent
      components. Averaging the time courses of spatially independent components time
      locked to stimulus presentation may prevent possible biases in the estimates of
      the spatial and temporal extent of stimulus-correlated activation and of trial-to
      trial variability.

PMID- 12204303
TI  - Estimating sample size in functional MRI (fMRI) neuroimaging studies: statistical
      power analyses.
AB  - Estimation of statistical power in functional MRI (fMRI) requires knowledge of
      the expected percent signal change between two conditions as well as estimates of
      the variability in percent signal change. Variability can be divided into intra
      subject variability, reflecting noise within the time series, and inter-subject
      variability, reflecting subject-to-subject differences in activation. The purpose
      of this study was to obtain estimates of percent signal change and the two
      sources of variability from fMRI data, and then use these parameter estimates in
      simulation experiments in order to generate power curves. Of interest from these
      simulations were conclusions concerning how many subjects are needed and how many
      time points within a scan are optimal in an fMRI study of cognitive function.
      Intra-subject variability was estimated from resting conditions, and inter
      subject variability and percent signal change were estimated from verbal working
      memory data. Simulations derived from these parameters illustrate how percent
      signal change, intra- and inter-subject variability, and number of time points
      affect power. An empirical test experiment, using fMRI data acquired during
      somatosensory stimulation, showed good correspondence between the simulation
      based power predictions and the power observed within somatosensory regions of
      interest. Our analyses suggested that for a liberal threshold of 0.05, about 12
      subjects were required to achieve 80% power at the single voxel level for typical
      activations. At more realistic thresholds, that approach those used after
      correcting for multiple comparisons, the number of subjects doubled to maintain
      this level of power.

PMID- 12204304
TI  - Hypothesis testing for selective, differential, and conjoined brain activation.
AB  - Hypothesis testing in functional neuroimaging studies relies heavily on the
      computation of categorical contrasts in which brain activation associated with
      one experimental condition is assessed relative to brain activation associated
      with a different experimental condition. Often, multiple pair-wise contrasts are
      computed and reported independently. Here we describe an approach to hypothesis
      testing that logically combines multiple pair-wise contrasts to distinguish among
      selective, differential and conjoined brain activation patterns. Using a sample
      dataset in which participants viewed objects, visual noise patterns or a fixation
      cross, we demonstrate that selective and differential brain activation patterns
      are often confounded with current approaches to hypothesis testing but that the
      logical combination approach can distinguish between these two types of data
      patterns. Specifically, we show that brain regions that respond selectively to an
      object recognition task relative to viewing visual noise or a fixation cross
      (selective activation) are mutually exclusive from brain regions that show a
      graded response to object viewing, noise viewing and visual fixation
      (differential activation). We thus show that the logical combination approach
      sufficiently constrains the results of categorical contrasts to reflect only the
      data pattern that would be predicted from the cognitive processing account under
      investigation.

PMID- 12204305
TI  - Functional MRI studies in awake rhesus monkeys: methodological and analytical
      strategies.
AB  - Functional imaging of the non-human primate brain in awake animals is now
      feasible because of recent methodological advances. Here we detail our procedures
      for conducting functional MRI (fMRI) studies in rhesus monkeys. Our emphasis has
      been on analyzing drug-evoked responses within and across test groups, meaning
      that techniques have had to be developed for training and testing relatively
      large groups of animals. Group size is important as unbiased estimates are best
      derived from analyzing responses in multiple animals with replicate scans per
      animal due to partial volume errors in evaluating small brain regions and motion
      artifacts during scanning. While the procedures presented here were developed for
      mapping responses obtained from stimulating dopaminergic systems, much of the
      methodology is generally applicable for non-human primate fMRI studies and
      addresses specific problems encountered in imaging awake animals. These are (1)
      adapting animals to an MRI environment, (2) minimizing head movements, (3)
      reducing ambient scanning noise levels, and (4) developing multivariate methods
      of image data analysis suitable for eliciting the dynamic brain response while
      (5) detecting and deleting outlying observations due to motion artifacts.
      Procedures are demonstrated for first pre-processing and analyzing responses in a
      voxel-based approach in a single animal and then proceeding to analyze responses
      across animals and replicate scans for regions of interest. Collectively, the
      procedures described provide an approach for fMRI mapping of elicited responses
      using conventional 1.5T MR scanners.

PMID- 12204306
TI  - Identification of determinism in noisy neuronal systems.
AB  - Most neuronal ensembles are nonlinear excitable systems. Thus it is becoming
      common to apply principles derived from nonlinear dynamics to characterize
      neuronal systems. One important characterization is whether such systems contain
      deterministic behavior or are purely stochastic. Unfortunately, many methods used
      to make this distinction do not perform well when both determinism and high
      amplitude noise are present which is often the case in physiological systems.
      Therefore, we propose two novel techniques for identifying determinism in
      experimental systems. The first, called short-time expansion analysis, examines
      the expansion rate of small groups of points in state space. The second, called
      state point forcing, derives from the technique of chaos control. The system
      state is forced onto a fixed point, and the subsequent behavior is analyzed. This
      technique can be used to verify the presence of fixed points (or unstable
      periodic orbits) and to assess stationarity. If these are present, it implies
      that the system contains determinism. We demonstrate the use and possible
      limitations of these two techniques in two systems: the Henon map, a classic
      example of a chaotic system, and spontaneous epileptiform bursting in the rat
      hippocampal slice. Identifying the presence of determinism in a physiological
      system assists in the understanding of the system's dynamics and provides a
      mechanism for manipulating this behavior.

PMID- 12204307
TI  - Intracellular ionic concentration by calibration from fluorescence indicator
      emission spectra, its relationship to the K(d), F(min), F(max) formula, and use
      with Na-Green for presynaptic sodium.
AB  - The emission spectra calibration curves for a fluorescence indicator and the
      F(min), F(max), and K(d) formula were shown to be related. Using the known
      calibrated fluorescence emitted by Sodium Green (Na-Green) and photo-multiplier
      tube quantum efficiency, we calculated the detection signal over a range of
      sodium concentrations. The calculated calibration curves were compared for
      optical filters passing a narrow band, medium band or full spectrum. We found
      that a method based on the full emission spectrum was the most appropriate. Given
      a known resting concentration of intracellular sodium, calibrated readings can be
      converted to concentration values. This method is applicable to any fluorescence
      indicator when curves for emission spectra over a range of concentrations are
      available. We measured sodium concentration changes during trains of action
      potentials (APs) at a crayfish motor axon's presynaptic terminals injected with
      Na-Green. During low frequency AP trains, net sodium increases asymptotically
      with frequency. Average net Na-flux per AP decreases for increasing terminal
      size. The terminals of crayfish motor axon have surface area to volume ratio
      which is 7700 times larger than for squid. Thus, in comparison to squid, crayfish
      terminals exhibit a larger change in [Na(+)](i) during equivalent AP activity.

PMID- 12204308
TI  - High-throughput behavioral screening method for detecting auditory response
      defects in zebrafish.
AB  - We have developed an automated, high-throughput behavioral screening method for
      detecting hearing defects in zebrafish. Our assay monitors a rapid escape reflex
      in response to a loud sound. With this approach, 36 adult zebrafish, restrained
      in visually isolated compartments, can be simultaneously assessed for
      responsiveness to near-field 400 Hz sinusoidal tone bursts. Automated, objective
      determinations of responses are achieved with a computer program that obtains
      images at precise times relative to the acoustic stimulus. Images taken with a
      CCD video camera before and after stimulus presentation are subtracted to reveal
      a response to the sound. Up to 108 fish can be screened per hour. Over 6500 fish
      were tested to validate the reliability of the assay. We found that 1% of these
      animals displayed hearing deficits. The phenotypes of non-responders were further
      assessed with radiological analysis for defects in the gross morphology of the
      auditory system. Nearly all of those showed abnormalities in conductive elements
      of the auditory system: the swim bladder or Weberian ossicles.

PMID- 12204309
TI  - A reliable primary human CNS culture protocol for morphological studies of
      dendritic and synaptic elements.
AB  - Primary dissociated human fetal forebrain cultures were grown in defined serum
      free conditions. At 4 weeks in vitro the cultures contained abundant
      morphologically well differentiated neurons with complex dendritic arbors.
      Astrocytic proliferation was negligible without the use of antimitotic agents.
      Confocal scanning laser microscopy (CSLM) and electron microscopy confirmed the
      presence of a dense neuropil, numerous cell-cell contacts and synapses. Neurons
      expressed a variety of proteins including growth associated protein-43 (GAP43),
      microtubule associated protein-2ab (MAP), class-III beta tubulin (C3BT),
      neurofilaments (NF), synaptophysin (SYN), parvalbumin (PA) and calbindin (CB).
      The cultures have proven to be reliable and simple to initiate and maintain for
      many weeks without passaging. They are useful in investigations of dendritic
      growth and injury of primary human CNS neurons.

PMID- 12204310
TI  - A new reproducible focal cerebral ischemia model by introduction of
      polyvinylsiloxane into the middle cerebral artery: a comparison study.
AB  - A reliable focal cerebral ischemia model is essential in evaluating the efficacy
      and safety of neuroprotective therapy for stroke. We present a focal embolic
      ischemic model of rat with reproducible and predictable brain infarction by
      comparing it with two other most commonly used focal cerebral ischemia models. To
      produce embolic focal cerebral ischemia, 30 male Wistar rats were subjected to
      injection of 30 microl hydrophilic polyvinylsiloxane (PVS) or an autologous
      thrombus or intraluminal filament occlusion in the right middle cerebral artery
      (MCA) (n = 10 in each group). The percent of brain infarct volume at 48 h after
      ischemia, neurobehavioral score at 2 h before and after ischemia, intracranial
      hemorrhagic incidence, and premature reperfusion rate at 3 h after ischemia by
      MCA angiography were assessed respectively and compared between the focal
      cerebral models. We found that PVS-induced focal cerebral ischemia had more
      consistent brain infarct size with less dispersion (32.2+/-7.4%, CV = 0.23) than
      that with an intraluminal filament occlusion (27.6+/-11.4%, CV = 0.41) or an
      autologous thrombus embolization (27.2+/-11.8%, CV = 0.43). Injection of PVS also
      caused more severe neurobehavioral deterioration (3.8+/-0.4) than those produced
      by two other models (filament, 3.1+/-0.9, P = 0.02; thrombotic, 3.5+/-0.5, P =
      0.08). Additionally, animals with PVS-induced focal cerebral ischemia suffered
      less intracranial hemorrhage (PVS, 0/10, filament, 3/10, thrombotic, 3/10), and
      less premature reperfusion as determined by MCA angiography (PVS, 0/10, filament,
      4/10, thrombotic, 3/10). Our data suggests that permanent focal cerebral ischemia
      with high reproducibility and low mortality can be achieved by introducing PVS
      into the right MCA.

PMID- 12204311
TI  - A cumulative sum test for a peri-stimulus time histogram using the Monte Carlo
      method.
AB  - We have established a cumulative sum (CUSUM) test for a peri-stimulus time
      histogram (PSTH) for the case where a conditioning stimulus is delivered at a
      fixed interval after previous discharge of a motor unit. (We refer to this kind
      of PSTH as an 'arranged PSTH'). Expectations of the firing probability after the
      conditioning stimulus vary among the bins in this arranged PSTH, while the
      expectations among the bins are all the same in the original PSTH; thus, we could
      not apply conventional tests for statistical analysis. We, therefore, propose a
      novel CUSUM test that uses the Monte Carlo method. With this method, the range of
      the statistical scattering noise on a CUSUM is computationally found by
      simulating the statistical process in order to calculate the confidence interval.
      We verified this CUSUM test using both simulated and actual experiments. This
      paper presents the procedure for performing this new method, along with an
      example of its application.

PMID- 12204312
TI  - Toward a revised evolutionary adaptationist analysis of depression: the social
      navigation hypothesis.
AB  - Evolutionary biologists use Darwinian theory and functional design ("reverse
      engineering") analyses, to develop and test hypotheses about the adaptive
      functions of traits. Based upon a consideration of human social life and a
      functional design analysis of depression's core symptomatology we offer a
      comprehensive theory of its adaptive significance called the Social Navigation
      Hypothesis (SNH). The SNH attempts to account for all intensities of depression
      based on standard evolutionary theories of sociality, communication and
      psychological pain. The SNH suggests that depression evolved to perform two
      complimentary social problem-solving functions. First, depression induces
      cognitive changes that focus and enhance capacities for the accurate analysis and
      solution of key social problems, suggesting a social rumination function. Second,
      the costs associated with the anhedonia and psychomotor perturbation of
      depression can persuade reluctant social partners to provide help or make
      concessions via two possible mechanisms, namely, honest signaling and passive,
      unintentional fitness extortion. Thus it may also have a social motivation
      function.

PMID- 12204313
TI  - Risperidone in the treatment of mania: efficacy and safety results from a large,
      multicentre, open study in Spain.
AB  - BACKGROUND: A number of open studies and preliminary results of unpublished
      double-blind trials have suggested that the novel antipsychotic risperidone may
      be effective and well tolerated in the treatment of acute mania in bipolar
      disorder. METHODS: A total of 174 patients entered this large, open, multicentre
      trial. Inclusion criteria were: current manic, hypomanic or mixed episode (DSM
      IV), and a Young Mania Rating Scale (YMRS) score of >7. Assessments included the
      YMRS, Positive and Negative Syndrome Scale (PANSS), Hamilton Rating Scale for
      Depression (HAM-D), Clinical Global Impression (CGI), and Udvalg for Kliniske
      Undersogelser (UKU) subscale for neurological side effects. RESULTS: There were
      significant reductions (P<0.0001) on the YMRS, PANSS and HAM-D scores and a
      significant improvement (P<0.0001) in CGI ratings at the endpoint. There were no
      statistically significant increments in the severity of extrapyramidal symptoms
      according to the UKU. Risperidone was generally well tolerated. The mean dose of
      risperidone at the endpoint was 4.9+/-2.9 mg/day. CONCLUSIONS AND CLINICAL
      IMPLICATIONS: This open study provides further evidence that risperidone is safe
      and effective in combination with mood stabilisers in the manic phase of bipolar
      disorder. LIMITATIONS: The open design and the use of concomitant medications
      make unclear to what extent the positive results were entirely related to
      risperidone.

PMID- 12204314
TI  - A randomised, double-blind comparison of milnacipran and imipramine in the
      treatment of depression.
AB  - This multicentre, double-blind, randomised trial in 109 patients compared the
      efficacy and tolerance of the novel selective serotonin and noradrenaline
      reuptake inhibitor (SNRI) antidepressant milnacipran (50 mg twice daily, n=53)
      with the established tricyclic agent imipramine (75 mg twice daily, n=56) over a
      period of 6 weeks, in patients with major depression (Montgomery-Asberg
      depression rating score (MADRS) > or =25). Initiation of antidepressant
      medication was conducted during a 2-week period of hospitalisation, after a 3- to
      7-day washout period. Concomitant psychiatric medication was limited to
      lorazepam, cyamemazine, chloral hydrate and long-term uncomplicated lithium
      therapy. Assessment for efficacy using the MADRS and Hamilton rating scales of
      depression, a visual analogue scale and global evaluation revealed both agents to
      be highly effective (P=0.0001) in this group of patients. Milnacipran was found
      to be of similar efficacy to imipramine. Tolerance, assessed by physiological and
      biochemical examinations with routine inventory and spontaneous report of adverse
      events, revealed a clear advantage for milnacipran. The incidence of
      anticholinergic events with milnacipran was about half that with imipramine and
      the overall incidence of adverse events by either reporting method was markedly
      lower with milnacipran than with imipramine. Furthermore, the patient drop-out
      rate with imipramine was double that experienced with milnacipran. Milnacipran
      appears to possess equal antidepressant efficacy to imipramine but with markedly
      superior tolerance. Therefore, milnacipran constitutes an important new treatment
      option in major depression.

PMID- 12204315
TI  - Childhood adversity, gender and depression over the life-course.
AB  - BACKGROUND: Full investigation of hypotheses concerning early risk factors and
      episodes of depression in adult life requires consideration of the separate risks
      of first onset and of recurrent episodes. This paper is based upon such an
      investigation. METHODS: A sample of participants in a large-scale population
      study (n=3491) provided information through retrospective assessment of lifetime
      history of (putative) major depressive disorder and of their adverse experiences
      in childhood. A statistical model based on Poisson regression, that combined both
      the (survival) distribution of first onset times with the subsequent rate of
      episode recurrence was specified to permit investigation of the gender difference
      in lifetime depression and the influence of childhood adversities on adult
      depression. RESULTS: A gender difference (with women at increased risk) was
      revealed for first onsets of depression only and was found to decrease with
      increasing age, being no longer apparent in those aged over 50. Experience either
      of a frightening event or of physical abuse in childhood was associated with an
      increased risk of first onset in younger adults (those aged < or =30).
      LIMITATIONS: The method of data collection used in this study warrants some
      caution in the interpretation of substantive findings. CONCLUSIONS: The
      relationships revealed concerning the risk for early and for late first onset and
      the risk of recurrence suggest different causal pathways underlying the
      associations between risk factors experienced early in life and depression in
      adulthood. Analyses that take full account of episode history can aid
      understanding of the origins of depression in adulthood.

PMID- 12204316
TI  - A study on nitric oxide, beta-adrenergic receptors and antioxidant status in the
      polymorphonuclear leukocytes from the patients of depression.
AB  - BACKGROUND: alterations in the polymorphonuclear leukocyte (PMNs) receptors,
      second messenger system and in their responses have been found associated with
      depression. Recently role of tetrahydrobiopterin and nitric oxide has also been
      reported in the depressive disorders. It was therefore considered worthwhile to
      investigate the NOS activity in the PMNs, which like neurons, also express
      neuronal NOS (nNOS), antioxidant enzyme levels [superoxide dismutase (SOD),
      catalase and glutathione peroxidase (Gpx)] and beta-adrenergic receptors in the
      patients of depression. METHODS: patients were diagnosed according to the DSM-IV
      and were medication free, while healthy age-matched controls were also included
      in the study to estimate nitrite content, beta-adrenergic receptors and
      antioxidant enzymes in the PMNs according to the standard methodologies. RESULTS:
      an analysis of 66 cases of depression and 114 controls revealed 73% decrease in
      nitrite content and 71% decrease in beta-adrenergic receptor binding in the
      patients as compared to the healthy controls. However, activities of SOD,
      catalase and Gpx were not significantly altered in the patients. CONCLUSION: the
      results of the present study for the first time indicate alterations the NOS
      activity in PMNs obtained form the patients of affective disorders.

PMID- 12204317
TI  - The identification of depression and the coverage of antidepressant drug
      prescriptions in Italian general practice.
AB  - BACKGROUND: Studies on antidepressant prescriptions in general practice need to
      assess the level of prescriptions relative to the need for them ('coverage'), and
      the variability among doctors. METHODS: Two different cut-off scores on a
      screening test for depression (the Personal Health Questionnaire, PHQ) are used
      to predict rates for depression, and rates for depressive patients thought likely
      to benefit from antidepressants (according to a severity criterion) in primary
      care patients. These two rates are compared with assessments by 11 GPs of
      recognised depression, as well as with rates of drug prescribed. RESULTS: The
      rate for depression thought likely to be treated with antidepressants estimated
      with the PHQ is broadly comparable with the rate for conspicuous depressive
      illness, and much lower than that predicted by the PHQ for depression. There was
      great variability between GPs in their ability to detect depression, and their
      preparedness to prescribe antidepressants. Antidepressants were only prescribed
      for 3.5% of the patients, compared to the 8.9% thought to need them. However,
      antidepressants, mostly SSRIs, are much more likely to be prescribed than
      tranquillisers. LIMITATIONS: The limitations of the study are that the PHQ is
      able to estimate 'coverage' but not 'focusing' (the proportion of those receiving
      antidepressants who needed them). CONCLUSIONS: Although the rate for conspicuous
      depression is similar to that for depressions thought to be treated with
      antidepressants, the 'coverage' of antidepressants was only 39.3%. The
      variability between physicians confirm the need of good practice guidelines and
      training packages for the identification and management of depression. Large
      epidemiological studies are needed to overcome the current lack of clinically
      relevant data on the quality of antidepressant prescriptions in general practice.

PMID- 12204318
TI  - EEG mapping in seasonal affective disorder.
AB  - Given that the nature of hemispheric dysfunction is different in heterogeneous
      disorders, in the present investigation EEG power mapping was applied to
      establish neurophysiological profiles that might potentially discriminate
      patients with seasonal affective disorder (SAD) among other affective disorders.
      The baseline resting EEG activity was recorded from 31 depressed SAD patients and
      30 controls. Power in the delta, theta-1, theta-2, alpha, beta-1 and beta-2
      frequency bands was extracted by Fourier transformation. Patients were found to
      have a lower delta (in central, parietal, occipital, temporal, posterior-temporal
      areas), theta-1 (in central and parietal), theta-2 (in anterior-frontal,
      parietal, occipital) and alpha activity (in anterior-frontal, midfrontal,
      central, parietal and occipital areas) than controls. SAD subjects showed,
      compared to controls, an asymmetrical distribution of delta, theta-1, theta-2 and
      alpha activity in parietal and temporal regions due to an increase of EEG power
      over the right electrode sites, and beta activity in the lateral frontal region
      due to an increase of beta power over the right electrode site. It is assumed
      that differential hemispheric contributions of EEG spectra may discriminate
      between the varieties of depression or different depressive states.

PMID- 12204319
TI  - The importance of psychosocial factors, gender, and severity of depression in
      distinguishing between adjustment and depressive disorders.
AB  - BACKGROUND: This study evaluated the severity of depressive symptomatology as it
      relates to: (a) sociodemographic factors and (b) the occurrence and type of acute
      and chronic psychosocial triggers or life events before admission. METHODS: In
      total, 718 psychiatric inpatients were assessed with the AMDP-system by the
      treating psychiatrist within the first 2 days after admission. RESULTS: In the
      females, sociodemographic factors (being married, children in the household,
      higher education and the quality of interactions) but not psychosocial stressors
      or life events were found to be related to severity of depression on admission.
      Females showed more severe depressive syndromes than males, however, depression
      severity in males was independent of sociodemographic factors, life events or
      psychosocial triggers. LIMITATIONS: Clinical assessment was based on
      retrospective history taking. The sample consisted of inpatients only, the
      results require replication using larger and more diverse samples. CONCLUSION:
      Gender differences and life conditions such as familial distress are related to
      severity of depression. The present criteria for the differentiation between
      depressive disorders and adjustment disorders are not independent and should be
      substituted by a multiaxial assessment.

PMID- 12204320
TI  - Vitamin E and depressive symptoms are not related. The Rotterdam Study.
AB  - OBJECTIVE: To investigate the reported association between low vitamin E levels
      and depressive symptoms in a population-based study. METHODS: The study is based
      on a cohort of 3884 adults aged 60 years and over who participated in the third
      survey of the Rotterdam Study, were screened for depressive symptoms with the
      Center of Epidemiological Studies Depression Scale and from whom blood was drawn.
      All screen-positive subjects had a psychiatric work-up. Blood levels of vitamin E
      were compared between 262 cases with depressive symptoms and 459 randomly
      selected reference subjects. All analyses were stratified by sex, and adjusted
      for age, cholesterol, cognitive score, smoking, dietary supplement use, marital
      status, living alone, and functional disability score. RESULTS: Vitamin E levels
      in men with depressive symptoms were lower than in non-depressed men after
      adjusting for age, whereas no such difference was found in women. This
      association in men was substantially weakened after controlling for biological
      factors, and disappeared with additional adjustment for nutritional behaviour and
      social factors. No differences were observed when the analyses were restricted to
      cases with depression as defined in the Diagnostic and Statistical Manual of
      Mental Disorders IV. CONCLUSIONS: After control for several biological and
      behavioural factors relating to health we found no association between low
      vitamin E levels and depressive symptoms or depression in the elderly.

PMID- 12204322
TI  - Measuring psychomotor agitation by use of an actimeter: a pilot study.
AB  - BACKGROUND: Psychomotor agitation is variably defined, with differing emphases on
      subjective and motor components. We assess the utility of an actimeter to inform
      us about aspects of the motor component. METHODS: A wrist actimeter measured
      motor activity of three inpatients with agitated depression. RESULTS: For each
      patient, diurnal activity patterns were observed, with activity generally
      elevated in mornings and late afternoons. Each patient also evidenced a clear
      decline in motor activity in the mid-evening, with little or no activity recorded
      during 'sleep' hours. Thus, psychomotor agitation (like motor activity) appears
      to require a conscious state. LIMITATIONS: Actimeters measure any baseline
      activity together with any superimposed movement component (which may range from
      movement changes to medication effects), making it difficult to disentangle
      components. We studied few patients and for brief intervals.

PMID- 12204321
TI  - A randomised, controlled trial of fluoxetine in methadone maintenance patients
      with depressive symptoms.
AB  - BACKGROUND: Depression and antidepressant use are prevalent in methadone
      maintenance patients (MMPs). However, antidepressant efficacy is not well
      established in this population. This study examined the efficacy of fluoxetine in
      improving depressive symptoms and reducing substance use in MMPs. METHODS:
      Stabilised MMPs scoring over 21 on the Beck Depression Inventory were randomised
      to receive fluoxetine or placebo over 12 weeks. RESULTS: Forty-nine subjects were
      randomised. In both groups, significant improvements were observed in depression,
      life functioning, and social impairment over 12 weeks. Poly-drug use improved in
      completers only. No fluoxetine effects were observed. CONCLUSIONS: Little
      evidence supports use of fluoxetine as a treatment for depressive symptoms in
      MMPs.

PMID- 12204323
TI  - Loss of the circadian variation of platelet [3H]imipramine binding in delusional
      compared with non-delusional endogenously depressed patients.
AB  - BACKGROUND: The circadian variations of the serotonin reuptake sites were studied
      in 16 patients meeting DSM-IV criteria for major depression with melancholia,
      either with (n=8) or without (n=8) psychotic symptomatology. METHOD: The
      [3H]imipramine binding sites were measured in platelet samples. RESULTS: While no
      statistically significant difference was found between the morning (09:00 h) and
      evening (21:00 h) [3H]imipramine B(max) values in the control group, both the non
      delusional and delusional melancholic patients showed higher evening than morning
      B(max) values, which were only statistically significant in the former. When both
      diagnostic groups were compared, the delusional patients showed significantly
      lower [3H]imipramine binding values than the non-delusional patients both in the
      morning and evening samples. Within the non-delusional depressed patients, those
      individuals with mood circadian variation, assessed by the 18th item of the HDRS,
      showed significantly lower B(max) values than those without mood variation.
      Lowest morning and evening B(max) values were noted in the delusional depressed
      group without mood variations. CONCLUSIONS: These results suggest that delusional
      depressions might have a different neurobiological substrate with loss of
      chronobiological rhythms.

PMID- 12204325
TI  - Protective effect of pregnancy on the course of lithium-responsive bipolar I
      disorder.

PMID- 12204326
TI  - Enhanced delivery of naked DNA to the skin by non-invasive in vivo
      electroporation.
AB  - DNA delivery to skin may be useful for the treatment of skin diseases, DNA
      vaccinations, and other gene therapy applications requiring local or systemic
      distribution of a transgene product. However, the effective, consistent and
      patient-friendly transfection of skin cells remains a challenge. In a mouse
      model, we evaluated the effectiveness of intradermal injection of plasmid DNA
      followed by noninvasive in vivo electroporation (EP) as a method to improve
      transfection in skin. We achieved a several hundred-fold stimulation of gene
      expression by EP, sufficient to produce clinically relevant amounts of transgene
      product. We studied the effect of DNA dose and time after treatment as well as
      various EP pulse parameters on the efficiency of gene expression. EP under
      conditions of constant charge transfer revealed that the applied voltage was the
      main determinant for transgene expression efficiency while other pulse parameters
      had lesser effects. Patient-friendly, noninvasive meander electrodes which we
      designed for clinical applications proved equally effective and safe as plate
      electrodes. We also showed for the first time that noninvasive EP is effective in
      stimulating transfection and gene expression in human skin, particularly in the
      epidermis. Our findings demonstrate the applicability of EP-enhanced DNA delivery
      to skin for gene therapy, DNA immunization and other areas.

PMID- 12204327
TI  - Purification and characterisation of two exo-polygalacturonases from Aspergillus
      niger able to degrade xylogalacturonan and acetylated homogalacturonan.
AB  - Two exo-polygalacturonases (EC 3.2.1.67) were purified from a commercial
      Aspergillus niger enzyme preparation by ammonium sulfate precipitation,
      preparative electrofocusing, anion-exchange and size-exclusion chromatographies.
      The enzymes had molar masses of 82 kDa (exo-PG1) and 56 kDa (exo-PG2). Exo-PG1
      was stable over wider pH and temperature ranges than exo-PG2. Addition of 0.01 mM
      HgCl(2) increased the exo-PG2 activity 3.4 times but did not affect exo-PG1.
      Analysis of the reaction products of (reduced) pentagalacturonate by high
      performance anion-exchange chromatography revealed that both enzymes split the
      substrate from the non-reducing end in a multi-chain attack mode. Exo-PG1 had a
      broad specificity towards oligogalacturonates with different degrees of
      polymerisation, while digalacturonate was the most favorable substrate for exo
      PG2. Both enzymes degraded xylogalacturonan from pea hull in an exo manner to
      produce galacturonic acid and Xyl-GalA disaccharide, as identified by
      electrospray ionization-ion trap mass spectrometry (ESI-ITMS). Moreover, exo-PGs
      split acetylated homogalacturonan in an exo manner, producing galacturonic acid
      and acetylated galacturonic acid, as shown by ESI-ITMS.

PMID- 12204328
TI  - Heat denaturation enhanced immunoglobulin production stimulating activity of
      lysozyme from hen egg white.
AB  - Lysozyme from hen egg white was identified as an immunoglobulin production
      stimulating factor (IPSF) that enhances immunoglobulin production by hybridomas
      and lymphocytes. The IPSF activity of lysozyme was facilitated by heat treatment.
      The heat treatment of lysozyme at 83 degrees C for 30 min activated its specific
      IPSF effect 30.0-fold compared with that of native lysozyme. The IPSF activity of
      lysozyme heat-treated at 83 degrees C in 4 M urea solution was enhanced 8.4-fold
      than that of native lysozyme. However, lysozyme that was not heated in 4 M urea
      solution completely lost its IPSF activity. This means that the IPSF activity of
      this enzyme in 4 M urea was reactivated by thermal treatment. Moreover,
      coexistence of 0.5 mM 2-mercaptoethanol (2-ME) during heating in 4 M urea
      solution extremely enhanced the IPSF activity up to 77.8-fold. The uptake of
      lysozyme by hybridoma cells was enhanced by heat denaturation in 4 M urea. The
      hydrophobicity of lysozyme was extremely increased by heat-treatment in 2-ME
      containing urea solution. It is expected from these findings that the increase in
      the hydrophobicity caused the enhancement of incorporation of lysozyme into
      target cells, and resulted in the acceleration of IgM production.

PMID- 12204329
TI  - Procyanidins protect Fao cells against hydrogen peroxide-induced oxidative
      stress.
AB  - In this paper, we evaluate the extent to which flavonoids in red wine (catechin,
      epicatechin, quercetin and procyanidins) protect against hydrogen peroxide
      induced oxidative stress in Fao cells. When cells were exposed to H(2)O(2),
      malondialdehyde (MDA) levels, oxidized glutathione (GSSG) levels and lactate
      dehydrogenase (LDH) release increased, indicating membrane damage and oxidative
      stress. All the flavonoids studied, and in particular epicatechin and quercetin,
      protected the plasma membrane. Only procyanidins lowered MDA levels and LDH
      leakage, maintained a higher reduced/oxidized glutathione ratio, and increased
      catalase/superoxide dismutase and glutathione peroxidase/superoxide dismutase
      ratios, and glutathione reductase and glutathione transferase activities. These
      results show that the procyanidin mixture has a greater antioxidant effect than
      the individual flavonoids studied, probably due to its oligomer content and/or
      the additive/synergistic effect of its compounds. This suggests that the mixture
      of flavonoids found in wine has a greater effect than individual phenols, which
      may explain many of the healthy effects attributed to wine.

PMID- 12204330
TI  - Thermodynamics of hCG--monoclonal antibody interaction: an analysis of real time
      kinetics data obtained using radiolabeled hCG probe.
AB  - A thermodynamic analysis of the interaction of 125I-labeled human chorionic
      gonadotropin (IhCG) with two of its monoclonal antibodies (MAbs) was carried out.
      The dissociation profile of IhCG-MAb complex conforms to a two-step model. vant
      Hoff enthalpies were calculated with the K(A) (equilibrium constant) values
      obtained from dissociation at different temperatures. Free energy and entropy
      changes were calculated using the standard equations. DeltaH values for one of
      the MAbs, viz. VM7 were favorable at temperatures beyond 30 degrees C.
      Interestingly, the DeltaS values were also favorable at all temperatures. In the
      case of MAb VM4a, however, the interaction throughout the temperature range was
      driven by large favorable entropic contributions, indicating the importance of
      hydrophobic interaction in the binding of this MAb to hCG. The energetics of the
      interaction of these two monoclonals with hCG is discussed.

PMID- 12204331
TI  - Single-stranded DNA condensed with poly-L-lysine results in nanometric particles
      that are significantly smaller, more stable in physiological ionic strength
      fluids and afford higher efficiency of gene delivery than their double-stranded
      counterparts.
AB  - Nonviral gene transfer vectors have been actively studied in the past years in
      order to obtain structural entities with minimum size and defined shape. The
      final size of a gene transfer vector, which is compacted into unimolecular
      complexes, is directly proportional to the mass of the nucleic acid to be
      compacted. Thus, the purpose of this study was to assess the possibility of
      producing ssDNA vectors and their biophysical and biological characterization. We
      have obtained ssDNA/poly-L-lysine complexes that are significantly smaller than
      their double-stranded counterparts. We have also identified a lesser aggregative
      behavior of compacted single-stranded vs. double-stranded DNA vectors in the
      presence of physiological NaCl concentrations. Expression of compacted ssDNA is
      observed in hepatoma cell lines. Moreover, we have successfully delivered
      galactosylated ssDNA complexes into cells that express the asialoglycoprotein
      receptor via receptor-mediated endocytosis. The reduced size and biophysical
      behavior of ssDNA vectors may provide an advantage for transfection of eukaryotic
      cells.

PMID- 12204332
TI  - Hemophilia A and B are associated with abnormal spatial dynamics of clot growth.
AB  - To gain greater insight into the nature of the bleeding tendency in hemophilia,
      we compared the spatial dynamics of clotting in platelet-free plasma from healthy
      donors and from patients with severe hemophilia A or B (factor VIII:C or
      IX:C<1%). Clotting was initiated via the intrinsic or extrinsic pathway in a thin
      layer of nonstirred plasma by bringing it in contact with the glass or fibroblast
      monolayer surface. The results suggest that clot growth is a process consisting
      of two distinct phases, initiation and elongation. The clotting events on the
      activator surface and the preceding period free of visible signs of clotting are
      the initiation phase. In experiments with and without stirring alike, this phase
      is prolonged in hemophilic plasma activated by the intrinsic, but not the
      extrinsic pathway. Strikingly, both hemophilia A and B are associated with a
      significant deterioration in the elongation phase (clot thickening), irrespective
      of the activation pathway. The rate of clot growth in hemophilic plasma is
      significantly lower than normal and declines quickly. The resulting clots are
      thin, which may account for the bleeding disorder.

PMID- 12204334
TI  - Endocytosis is involved in DNA uptake in yeast.
AB  - The transfection of mammalian cells by endocytosis is frequently hampered by low
      efficiency. To identify the bottlenecks, a system that allows the analysis of the
      intracellular pathway of DNA along the endocytic compartments in the eukaryote
      Saccharomyces cerevisiae was developed. DNA uptake in yeast cells was achieved by
      endocytosis when the cells were incubated with episomal DNA in the presence of
      34% sucrose and subsequently shifted to a hypotonic medium to induce osmotical
      lysis of accumulated endocytic intermediates. The compartments of the endocytic
      pathway after the intersection of the endocytic and the vacuolar sorting pathway
      are preferred sites of DNA degradation. Either a transport blockade before this
      point or, even better, the presence of chloroquine, which is known as an adjuvant
      for transfection in mammalian cells, are required for successful transfection.
      The transport blockade can be achieved by deleting a GTPase of the endocytic
      pathway, Ypt51p, or ethanol. Chloroquine affects the compartments of the late
      endocytic pathway, and no effect is seen on transfection in a strain that is
      defective for YPT51 and accumulates the DNA in the early endocytic intermediates.
      To our knowledge, this is the first report on endocytic DNA uptake in S.
      cerevisiae.

PMID- 12204333
TI  - Can ginsenosides protect human erythrocytes against free-radical-induced
      hemolysis?
AB  - Many studies have focused on the free-radical-initiated peroxidation of membrane
      lipid, which is associated with a variety of pathological events. Panax ginseng
      is used in traditional Chinese medicine to enhance stamina and capacity to deal
      with fatigue and physical stress. Many reports have been devoted to the effects
      of ginsenosides, the major active components in P. ginseng, on the lipid
      metabolism, immune function and cardiovascular system. The results, however, are
      usually contradictory since the usage of mixture of ginsenosides cannot identify
      the function of every individual ginsenosides on the experimental system. On the
      other hand, every individual ginsenosides is not compared under the same
      experimental condition. These facts motivate us to evaluate the antioxidant
      effect of various individual ginsenosides on the experimental system of free
      radical-initiated peroxidation: the hemolysis of human erythrocyte induced
      thermally by water-soluble initiator, 2,2'-azobis(2-amidinopropane hydrochloride)
      (AAPH). The inhibitory concentration of 50% inhibition (IC(50)) of AAPH-induced
      hemolysis of the erythrocyte has been studied firstly and found that the order of
      IC(50) is Rb3 - Rb1<<Rg2<Re<Rg1 - Rc<Rh1<R1. Rb1, Rc and Rg2, as antioxidants,
      can prolong the lag time of hemolysis. Contrarily, Rg3, Rd and Rh1, together with
      high concentration of Rb3, Rg1 and Rh2, function as prooxidants to accelerate
      AAPH-induced hemolysis. The addition of Re does not influence the lag time of
      hemolysis. The R1 with the concentration ranging from 10 to 20 microM decreases
      the lag time of hemolysis. These results suggest that there is a mutual
      interaction that existed in the molecule of ginsenosides since the difference of
      the structure of ginsenosides is only due to the connective position and type of
      sugar moieties to the ring of a triterpene dammarane. Moreover, the synergistic
      antioxidative properties of various individual ginsenosides with alpha-tocopherol
      (TOH) are also discussed, and it was found that the order of synergistic
      antioxidative properties with TOH is Rb1>Rc>Re>Rh1>R1>Rg2>Rb3. Rg3, Rd and Rh2,
      however, act as synergistic prooxidants in the above experimental system. Rg1
      does not show any synergistic antioxidative property. Although the antioxidative
      and prooxidative mechanism of various ginsenosides with or without TOH in AAPH
      induced hemolysis of human erythrocytes will be further studied in detail, this
      information may be useful in the clinical usage of ginsenosides.

PMID- 12204335
TI  - Electrophoretic and immunochemical study of collagens from Sepia officinalis
      cartilage.
AB  - Electrophoretic and Western blot studies were conducted on collagen fractions
      extracted from Sepia officinalis (cuttlefish) cartilage using a modified salt
      precipitation method developed for the isolation of vertebrate collagens. The
      antibodies used had been raised in rabbit against the following types of
      collagen: Sepia I-like; fish I; human I; chicken I, II, and IX; rat V; and calf
      IX and XI. The main finding was that various types of collagen are present in
      Sepia cartilage, as they are in vertebrate hyaline cartilage. However, the main
      component of Sepia cartilage is a heterochain collagen similar to vertebrate type
      I, and this is associated with minor forms similar to type V/XI and type IX. The
      cephalopod type I-like heterochain collagen can be considered a first step toward
      the evolutionary development of a collagen analogous to the typical collagen of
      vertebrate cartilage (type II homochain). The type V/XI collagen present in
      molluscs, and indeed all phyla from the Porifera upwards, may represent an
      ancestral collagen molecule conserved relatively unchanged throughout evolution.
      Type IX-like collagen seems to be essential for the formation of cartilaginous
      tissue.

PMID- 12204336
TI  - Kinetic studies on the hydrogen peroxide elimination by cultured PC12 cells: rate
      limitation by glucose-6-phosphate dehydrogenase.
AB  - Oxidative stress is implicated in the pathogenesis of neurodegenerative disorders
      and brain ischemia, and hydrogen peroxide (H(2)O(2)) plays a central role in the
      stress. In this study, we have examined the kinetics of H(2)O(2) elimination by
      PC12 cells as a neuronal model in connection with the enzyme activities
      supporting the reaction. Similarly to other cell lines previously studied,
      H(2)O(2) removal kinetics could be divided into two reactions: one apparently
      following the Michaelis-Menten kinetics (GSH-dependent reaction) and the other
      following the first-order kinetics (mainly catalyzed by catalase). Based on the
      enzyme activities in the cell homogenate, it was inferred that glucose-6
      phosphate dehydrogenase (G6PD) is the rate-limiting enzyme in the GSH- and NADPH
      dependent H(2)O(2) elimination by PC12 cells. This is in contrast with
      fibroblasts and endothelial cells previously examined, in which glutathione
      reductase (GR) is rate-limiting in the reaction sequence. Treatment of PC12 cells
      with nerve growth factor increased G6PD activity in the cell homogenate and
      H(2)O(2) removal activity of the whole cells, with a concomitant increase in the
      resistance against H(2)O(2) toxicity. These results suggest the importance of
      G6PD in the antioxidant function of brain and pathogenesis of the oxidative
      stress-related diseases.

PMID- 12204337
TI  - Formation of lysophospholipids from unsaturated phosphatidylcholines under the
      influence of hypochlorous acid.
AB  - The formation of lysophosphatidylcholines from unsaturated phosphatidylcholines
      upon treatment with hypochlorous acid was evaluated by means of MALDI-TOF mass
      spectrometry and 31P NMR spectroscopy. With an increasing number of double bonds
      in a fatty acid residue, the yield of lysophosphatidylcholines with a saturated
      fatty acid residue increased considerably in comparison to the total amount of
      higher molecular weight products like chlorohydrins and glycols. High amounts of
      lysophosphatidylcholines were formed from phospholipids containing arachidonic or
      docosahexaenoic acid residues. In phospholipids with monounsaturated fatty acid
      residues, the position of the double bond did not influence the yield of lyso
      products. Besides the exclusive formation of chlorohydrin and glycol,
      hypochlorous acid caused the cleavage of the unsaturated fatty acid residue
      independent of its location at the first or second position of the glycerol
      backbone. In contrast, strong alkaline conditions, i.e. saponification led also
      to a hydrolysis of the saturated fatty acid residue from phosphatidylcholines. It
      is concluded that both MALDI-TOF mass spectrometry and 31P NMR spectroscopy are
      able to detect the formation of lysophosphatidylcholines. We conclude also that
      the formation of lysophospholipids from unsaturated phosphatidylcholines by
      hypochlorous acid can be relevant in vivo under acute inflammatory conditions.

PMID- 12204338
TI  - Cell-to-cell communication in response of E. coli cells at different phases of
      growth to low-intensity microwaves.
AB  - Effects of millimeter waves (MMW) at the frequency of 51.755 GHz were studied in
      logarithmic and stationary E. coli cells at various cell densities. The changes
      in the genome conformational state (GCS) were analyzed by the method of anomalous
      viscosity time dependence (AVTD). Before lysis, the cells were adjusted to the
      cell density of 4x10(7) cells/ml and all AVTD measurements were run at this cell
      density. Stationary cells responded to MMW by increase in AVTD, while the same
      MMW exposure decreased AVTD in logarithmic cells. MMW effects depended on cell
      density during exposure and were stronger for stationary cells. The observed
      dependence on cell density suggested a cell-to-cell communication between cells
      during exposure to microwaves. Decrease in power density (PD) resulted in more
      striking differences between responses at different cell densities. The data
      provided evidence that intercellular communication in response to MMW depended on
      cell status and PD of microwaves. The MMW effects were studied in more detail at
      low intensity of 10(-17) W/cm(2) in the range of cell densities 4x10(7) to
      8x10(8) cells/ml. The obtained sigmoid-like dependence of MMW effect on cell
      density saturated at approximately 5x10(8) cells/ml. The dependence of MMW effect
      on cell density was very similar in this study and in previous studies with weak
      extremely low frequency (ELF) electromagnetic fields (EMF). The data suggested
      that cell-to-cell communication might be involved in response of cells to weak
      EMF of various frequency ranges.

PMID- 12204339
TI  - Kinetics and efficiency of excitation energy transfer from chlorophylls, their
      heavy metal-substituted derivatives, and pheophytins to singlet oxygen.
AB  - Time-resolved measurements of the singlet oxygen infrared (1269 nm) luminescence
      were used to follow the kinetics and efficiency of excitation energy transfer
      (EET) between chlorophyll (Chl) derivatives and oxygen in acetone. The studied
      pigments were Mg-Chl a and b and their heavy metal (Cu(2+) and Zn(2+))
      substituted analogues, as well as pheophytin (Pheo) a and b. The efficiency of
      EET from chlorophyll to oxygen was highly dependent on the central ion in the
      pigment. Cu-Chl a and Cu-Chl b had the lowest efficiencies of singlet oxygen
      production, while Pheo a had a higher one, and Zn-Chl a had a similar one
      compared to Mg-Chl a. Also the side chain (position C-7, i.e. Chl a vs. Chl b)
      influenced the efficiency of singlet oxygen formation. In the case of square
      planar complexes like Cu-Chl and Pheo, EET was more efficient in the Chl a
      derivatives than in those of Chl b; the opposite effect was observed in the case
      of the five- or six-coordinated Mg-Chl and Zn-Chl. As for the lifetime of the Chl
      triplet state, the most striking difference to Mg-Chl again was found in the case
      of Cu-Chls, which had much shorter lifetimes. Furthermore, the central ion in Chl
      affected the physical quenching of singlet oxygen: its efficiency was decreasing
      from Mg-Chl through Zn-Chl over Cu-Chl to Pheo. The results are discussed in the
      context of the oxidative stress accompanying heavy metal-induced stress in
      plants.

PMID- 12204340
TI  - RGD-CAP ((beta)ig-h3) is expressed in precartilage condensation and in
      prehypertrophic chondrocytes during cartilage development.
AB  - RGD-CAP ((beta)ig-h3), isolated from cartilage as a collagen-associated protein,
      was demonstrated to have a binding ability to collagen and to enhance the
      adhesion of chondrocytes via integrin alpha(1)beta(1). However, the role of this
      protein in cartilage development remains unclear. In this study, we investigated
      the expression of RGD-CAP ((beta)ig-h3) in chick embryos and cultured mesenchymal
      stem cells (MSCs) during the differentiation to chondrocytes. The effects of
      recombinant RGD-CAP on adhesion and DNA synthesis of MSCs and mineralization were
      also examined. Tissue sections from chick embryos at Hamburger-Hamilton (HH)
      stages 19-37 were immunostained with anti-chick RGD-CAP antibodies. The
      expression of RGD-CAP was slightest in chick embryos at HH stage 19, whereas a
      considerable expression of RGD-CAP was observed in the developing vertebrae and
      precartilage aggregate in the limb bud of chick embryos at HH stage 26. The
      expression of RGD-CAP was significantly reduced in vertebrae of chick embryo at
      HH stage 32. Reverse transcriptional polymerase chain reaction (RT-PCR) analysis
      showed that RGD-CAP was highly expressed in cultured MSCs and decreased by 4-day
      treatment with 10(-8) M dexamethasone when MSCs proliferated to adipocyte-like
      cells, whereas it was recovered by co-treatment with 3 ng/ml TGF-beta for 8-12
      days when MSCs proliferated to hypertrophic chondrocyte-like cells. The adhesion
      and DNA synthesis of MSCs cultured on RGD-CAP-coated dishes increased
      significantly compared with the controls. RGD-CAP was distributed in the
      prehypertrophic zone in matured cartilage of the vertebrae of chick embryos at HH
      stage 37. Recombinant RGD-CAP inhibited the mineralization of hypertrophic
      chondrocytes. These results suggest that RGD-CAP ((beta)ig-h3) exerts an
      essential role in the early cartilage development by enhancing the adhesion and
      growth of the pre-chondrogenic cells, and functions as a negative regulator for
      mineralization at the terminal stage of the chondrogenic differentiation.

PMID- 12204341
TI  - Higher radical scavenging activities of polyphenolic antioxidants can be ascribed
      to chemical reactions following their oxidation.
AB  - Radical scavenging activities of 34 natural antioxidants were investigated from
      an electrochemical viewpoint. While the correlation of the oxidation potentials
      with their DPPH radical scavenging activities (represented by EC(50)) was not
      high (the correlation coefficient, r=0.73), the number of electrons n required
      for oxidation of an antioxidant, being obtained by continuous flow-column
      electrolysis with a slower flow rate (0.05 ml min(-1)), did show a good
      correlation with EC(50) (1/EC(50)=1.67n+0.50 with r=0.94). The n values of most
      polyphenols were increased with a decrease in the flow rate, while those of
      nonpolyphenols were invariant. This suggests that a slower subsequent chemical
      reaction(s) should be involved in the oxidation of polyphenols, whose higher
      radical scavenging activities seem to be ascribed to the chemical reactions. In
      this study, we have proposed a possible mechanism for the oxidation of
      polyphenols, in which the oxidizable -OH moieties are reproduced through an
      oxidative dimerization (or more highly polymerization).

PMID- 12204342
TI  - Reaction of the spin trap 3,5-dibromo-4-nitrosobenzene sulfonate with human
      biofluids.
AB  - Using the spin trap 3,5-dibromo-4-nitrosobenzene sulfonate (DBNBS), an oxidant
      was previously detected in the plasma of patients with renal failure and the
      synovial tissue of rheumatoid arthritis patients. This oxidant has been shown to
      react with DBNBS to give a 3-line electron paramagnetic resonance (EPR) spectrum,
      previously assigned to the DBNBS radical cation (DBNBS*(+). However, confusion
      has arisen as to whether this paramagnetic species is indeed DBNBS*(+) or,
      rather, the DBNBS sulfite radical adduct (DBNBS-SO(3)*(-)). In the present study,
      DBNBS*(+) (a(N)=1.32 mT) was distinguished from DBNBS-SO(3)*(-) (a(N)=1.32 mT
      with an additional splitting of a(H)=0.06 mT) by (a) using different EPR
      parameters, (b) determining the effect of addition of sulfite on the EPR spectrum
      resulting from the incubation of DBNBS with either human biofluids or the
      horseradish peroxidase (HRP)-hydrogen peroxide (H(2)O(2)) system, and (c)
      replacing DBNBS with its analogues (DBNBS-d(2,) DBNBS-15N and DBNBS-d(2)-15N) in
      the two systems.

PMID- 12204343
TI  - A rapid method for measuring intracellular pH using BCECF-AM.
AB  - A rapid intracellular pH (pH(i)) measurement method based on initial rate of
      increase of fluorescence ratio of 2',7'-bis(2-carboxyethyl)-5,6
      carboxyfluorescein upon dye addition to a cell suspension in growth medium is
      reported. A dye transport model that describes dye concentration and fluorescence
      values in intracellular and extracellular spaces provides the mathematical basis
      for the approach. Experimental results of ammonium chloride challenge response of
      the two suspension cells, Spodoptera frugiperda and Chinese hamster ovary (CHO)
      cells, successfully compared with results obtained using traditional perfusion
      method. Since the cell suspension does not require any preparation, measurement
      of pH(i) can be completed in about 1 min minimizing any potential errors due to
      dye leakage.

PMID- 12204344
TI  - Mechanisms of flavonoid repair reactions with amino acid radicals in models of
      biological systems: a pulse radiolysis study in micelles and human serum albumin.
AB  - Neutral tryptophan (*Trp) and tyrosine (TyrO(*)) radicals are repaired by certain
      flavonoids in buffer, in micelles and in human serum albumin (HSA) with
      corresponding formation of semioxidized flavonoid radicals. In deaerated buffer,
      *Trp but not TyrO(*) radicals react with catechin. In micelles, quercetin and
      rutin repair both *Trp and TyrO(*) radicals. In addition to amino acid
      reactivity, microenvironmental factors and nature of the flavonoids govern this
      repair. Electron transfer efficiencies from quercetin to negatively charged *Trp
      radicals are 100% in the micellar pseudophases of positively charged
      cetyltrimethylammonium bromide, (CTAB), and neutral Triton X100 (TX100), but 55%
      in negatively charged sodium dodecyl sulfate (SDS). In oxygen-saturated CTAB
      micelles, quercetin also reacts with the superoxide radical anion. When bound to
      domain IIA of HSA, quercetin repairs, by intra- or intermolecular encounter, less
      than 20% of oxidative damage to HSA. Quercetin can also repair freely circulating
      oxidized molecules with repair efficiencies falling to 7% for oxidized Trp, Tyr
      and alpha-MSH and to less than 2% for urate radical. This limited effectiveness
      is attributed both to the inaccessibility of bound quercetin and rutin toward
      radicals of circulating molecules and to the diffusion-controlled recombination
      of these radicals.

PMID- 12204345
TI  - Morphology, GluR1 and GRIP-C localization differ in octopus cells of C57BL6 and
      B6Cast mice.
AB  - The C57BL6 mouse (B6) is homozygous for the gene for age-related hearing loss
      (ahl/ahl) and shows normal adult-like hearing before subtle changes in hearing
      begin at about 30 days of age. The B6Cast mouse is congenic to B6, having the
      wild type allele for normal hearing from Castaneous Ei on a B6 background. It has
      normal hearing throughout most of its lifespan. This study characterized the
      morphology of octopus cell (OC) somata in the posterior-ventral cochlear nucleus
      and of synaptic terminals on the OC somata in 8-week-old B6 and B6Cast mice, and
      the immunolocalization of antibodies to GluR1 (glutamate receptor subunit 1) and
      GRIP-C (glutamate receptor interacting protein-C terminus). By 8 weeks of age
      there are significant changes in the morphology of OCs and synaptic terminals
      around their somata in B6 mice compared to B6Cast mice. The distribution of
      immunoreactivity for the proteins GluR1 and GRIP is also significantly different
      in B6 mice from that in B6Cast mice. The modest degenerative changes reported in
      some B6 outer hair cells of the basal turn at this age do not seem adequate to
      explain the major changes observed in most OCs at a time when physiological
      studies show that many measures of the animals' hearing are still near normal.
      The findings suggest that changes in the alpha-amino-3-hydroxy-5-methyl-4
      isoxazole glutamate receptor subunits and/or their binding proteins are part of
      the phenotype of ahl, and may reflect a role of the glutamate receptor pathway in
      the mechanism of ahl.

PMID- 12204346
TI  - Tuning and timing of excitation and inhibition in primary auditory nerve fibers.
AB  - Information about the tuning and timing of excitation, adaptation and suppression
      in an auditory primary afferent axon can be obtained from the second-order Wiener
      kernel. Through the process of singular-value decomposition, this information can
      be extracted from the kernel and displayed graphically in separate two
      dimensional images for excitation and inhibition(1). For low- to mid-frequency
      units, the images typically include checkerboard patterns. For all units they may
      include patterns of parallel diagonal lines. The former represent non-linearities
      in the phase-locked (ac) response of the unit; the latter reflect non-linear
      envelope-following (dc) responses. Examples of detailed interpretation are
      presented for three amphibian-papillar units from the American bullfrog. The
      second-order Wiener kernel itself is derived from second-order reverse
      correlation between spikes and a continuous, non-repeating, broad-band white
      noise stimulus.

PMID- 12204347
TI  - Effects of nitric oxide synthase inhibitor on cochlear blood flow.
AB  - We observed in rats the changes in cochlear blood flow (CoBF) and cutaneous blood
      flow of the abdominal wall (AbBF) after the administration of the NO synthase
      inhibitor, N-nitro-L-arginine-methyl ester (L-NAME). Ten minutes after i.v.
      infusion of L-NAME (0.2, 1, 5, 10 mg/kg), L-arginine, which is a substrate of NO,
      was infused (100 mg/kg) i.v. Employing a laser Doppler flowmeter, the changes in
      blood flow were recorded from the basal turn of the right cochlea or the
      abdominal wall and blood pressure (BP) was recorded from the left femoral artery
      simultaneously. Vascular conductance (VC) was calculated from CoBF/mean BP
      (cochlear VC) or AbBF/mean BP (abdominal VC). The findings in rats generally
      agreed with those in guinea pigs [Brechtelsbauer et al., Hear. Res. 77 (1994) 38
      42]. Intravenous infusion of L-NAME produced a dose-dependent depression of
      cochlear VC at 0.2 mg/kg (-18.9), 1 mg/kg (-37.9%), 5 mg/kg (-45.8%) and 10 mg/kg
      (-48.3%). AbBF also decreased after infusion of L-NAME (5 mg/kg) but to a lesser
      degree (-41.1% in VC) with no significance compared to CoBF (5 mg/kg). Infusion
      of L-arginine partially reversed the CoBF decrease caused by L-NAME. The group of
      0.2 mg/kg infusion of L-NAME showed the largest degree of recovery with L
      arginine, while the 10 mg/kg group showed the smallest. The decrease in AbBF did
      not recover substantially with L-arginine, the degree being less than that of
      each group in the CoBF experiment. It was suggested that the NO/soluble guanylate
      cyclase/cGMP system is more active in the cochlear microcirculation. With the
      round window (RW) application of 1% L-NAME (2 microl), cochlear VC was decreased
      by 21.6%, which was closest to that of the 0.2 mg/kg group of L-NAME i.v.
      infusion. The cochlear VC depression after local application of L-NAME did not
      show any recovery (-0.3%) by RW application of 5% L-arginine (2 microl) 25 min
      after L-NAME application; a slight gradual increase was observed when a higher
      concentration (20%) of L-arginine was applied to the RW. We propose that i.v.
      infusions of L-NAME and L-arginine primarily affect the precapillary arteriole of
      the spiral modiolar artery which effectively regulates microcirculation as a
      resistance vessel, and that RW application affects the vessels of the lateral
      wall, not the spiral modiolar artery because of the difficulty of substance
      diffusion.

PMID- 12204348
TI  - Brain imaging of the effects of lidocaine on tinnitus.
AB  - Using a single-blind placebo-controlled design, we mapped lidocaine related
      changes in neural activity, measured by regional cerebral blood flow (rCBF) with
      (15)O-H(2)O positron emission tomography. Intravenous lidocaine produced both
      increases and decreases in the loudness of tinnitus. The change in tinnitus
      loudness was associated with a statistically significant change in neural
      activity in the right temporal lobe in auditory association cortex. Decreases in
      tinnitus loudness resulted in larger changes in rCBF than increases. The
      unilateral activation pattern associated with tinnitus, in contrast with the
      bilateral activation produced by a real sound, suggests that tinnitus originates
      in the central auditory system rather than the cochlea. In addition, generalized
      lidocaine effects were found in the basal ganglia, thalamus, and a region
      spanning the Rolandic fissure.

PMID- 12204349
TI  - Sodium- and potassium-activated ATPase in the mammalian vestibular system.
AB  - Autoradiographic and cytochemical procedures were employed to determine the
      cellular distribution of the Na,K-ATPase enzyme in the mammalian vestibular
      system. A light-microscope survey of vestibular tissues incubated with
      [(3)H]ouabain shows high densities of ouabain binding sites within the dark cell
      epithelium (DC) of the ampullae of the semi-circular canals, and to a lesser
      extent, the DC of the utricular macula. A moderate number of binding sites was
      found in nerve fibers penetrating the connective tissue beneath the sensory
      epithelium (SE) of the ampullae and the maculae. A small number of binding sites
      is distributed in the deep portion of the SE, both in the ampullae and in the
      maculae. These latter binding sites seem to be associated with nerve terminals
      and receptor cells. At the ultrastructural level, the vestibular dark cells
      exhibit extensive basolateral membrane infolding, a morphological hallmark of
      cells engaged in trans-epithelial ion transport. The cytochemical reaction
      product is K(+)-dependent, ouabain inhibitable, and is restricted to the
      basolateral membrane extensions, with little or no product on the luminal
      membrane. The extent of membrane infolding in dark cells of the utricle is less
      pronounced than that of the ampullar dark cells and the intensity of the
      cytochemical reaction appears to correlate with the extent of membrane infolding.
      The results support the widely held hypothesis that the vestibular dark cells
      play a role in endolymph production. They also suggest that the vestibular
      sensory epithelia may be a site of ion exchange.

PMID- 12204350
TI  - Perceptual correlates of neural plasticity related to spontaneous otoacoustic
      emissions?
AB  - The inner ear contains receptor cells that oscillate spontaneously, generating
      waves that propagate backward in the cochlea, ultimately causing sound to be
      radiated into the ear canal--the spontaneous otoacoustic emissions (SOAEs).
      Except in rare conditions, these internally generated signals appear to go
      unheard. The intensity of SOAEs admittedly hovers near the threshold of
      detection, but they are essentially continuous and perhaps last a lifetime. The
      hypothesis is tested that the frequency difference limen (DL(F)) is affected by
      SOAEs. The results show that the DL(F) systematically improves near SOAE
      frequencies, determined ipsi- or contralaterally to the SOAEs, arguing for a
      central effect. The results are discussed in the context of central plasticity.

PMID- 12204351
TI  - Neural adaptation to pulsatile acoustical stimulation in the cochlear nucleus of
      the rat.
AB  - This study, carried out in adult Long-Evans rats, was designed to investigate the
      adaptive properties of the cochlear nucleus to pulsatile acoustical stimuli. To
      achieve this purpose, near-field evoked potentials were picked up from the
      ventral cochlear nucleus in awake animals. Individual auditory thresholds were
      measured and responses to 250 ms trains of repetitive clicks with pulse rates
      ranging from 100 to 2000 pulses per second were collected. The amplitude of the
      first negative (N(1)) component of the evoked potentials to consecutive
      individual pulses in the train was measured by using a subtraction method. As
      expected, a rapid amplitude decrement of the responses in the train was obtained
      and a three phase adaptation was described. The decrease of individual N(1)
      component amplitude was fitted for each rate of stimulation with exponential
      decrease equations and time constants were calculated. Such an analysis allowed
      us to characterize three distinct adaptive processes which were discussed. The
      results were comparable to those obtained in previous studies in the auditory
      nerve and suggest that the adaptation recorded in the ventral cochlear nucleus by
      using near-field evoked potentials reflects the adaptive properties of auditory
      nerve fibers.

PMID- 12204352
TI  - Behavioral and evoked-potential thresholds in young and old Mongolian gerbils
      (Meriones unguiculatus).
AB  - Age-dependent hearing loss has been well documented in gerbils exceeding 2 years
      of age using physiological methods (e.g. [Mills et al. (1990) Hear. Res. 46, 201
      210]). We determined behavioral thresholds for broad-band noise and pure-tone
      pulses in gerbils as a function of age. Contrary to expectations based on
      previously published physiological data, we found no significant (broad-band
      noise and 10 kHz) or only a very small hearing loss (7 dB at 2 kHz) in 30-36
      month-old animals. In animals over 3 years of age we observed an increased spread
      of thresholds and threshold shifts exceeding 20 dB in some individuals.
      Behavioral thresholds of old gerbils from two breeding colonies (University of
      Regensburg and Medical University of South Carolina) were similar. Data from
      individual animals where thresholds were determined physiologically and
      behaviorally indicate that results from auditory brainstem response measurements
      show no shift at 18 months while subsequent measurements at 28-29 months revealed
      age-dependent threshold shifts of 10-15 dB. In contrast, thresholds determined by
      behavioral methods in these same individuals at 31-33 months of age remained
      stable.

PMID- 12204353
TI  - Hearing in American leaf-nosed bats. I: Phyllostomus hastatus.
AB  - We determined the audiogram of Phyllostomus hastatus (the greater spear-nosed
      bat), a large, omnivorous American leaf-nosed bat native to Central and South
      America. A conditioned suppression/avoidance procedure with a fruit juice reward
      was used for testing. At an intensity of 60 dB sound pressure level (SPL re 20
      microN/m(2)), the hearing range of P. hastatus extends from 1.8 to 105 kHz, with
      a best sensitivity of 1 dB SPL at 20 kHz. Both its high-frequency and low
      frequency hearing are not unusual for a small mammal. Despite its use of low
      intensity echolocation calls there was no evidence for unusual sensitivity to
      either the frequencies used for echolocation or to the main frequencies of its
      communication calls, suggesting no selective "tuning" of the audiogram. Its
      behavioral pure-tone thresholds are lower than the multi-unit thresholds in the
      inferior colliculus.

PMID- 12204354
TI  - Expression of Klotho protein in the inner ear.
AB  - The Klotho mouse is a recently developed model that exhibits phenotypes
      resembling human aging. We used this model to investigate sensorineural hearing
      loss from the point of view that it may be considered an issue of aging. Using
      reverse transcription-polymerase chain reaction, Western blotting and
      immunohistochemical staining, we were able to confirm klotho gene transcription
      and protein synthesis in the kidney and inner ear. Klotho protein was mainly
      expressed in the stria vascularis and spiral ligament of the inner ear and in the
      distal convoluted tubule of the kidney, likely serving a common function in the
      two organs, i.e., modulating ion transport. The threshold for the auditory
      brainstem response was significantly higher in Klotho mice than in wild-type
      mice, and wave I latencies were prolonged. On the other hand, Klotho mice
      exhibited a normal distribution of I-IV interpeak intervals. No obvious
      morphological abnormalities were detected in Klotho mice, although no expression
      of Klotho protein was detected, and there was an apparent hearing disorder. Taken
      together, these findings suggest that by contributing to the maintenance ion
      homeostasis in the endolymph, Klotho protein serves as a key mediator of auditory
      function.

PMID- 12204355
TI  - Behavioral audiograms of homozygous med(J) mutant mice with sodium channel
      deficiency and unaffected controls.
AB  - Complete behavioral audiograms were determined for med(J) mice (F1 offspring of
      C57BL/6JxC3HeB/FeJ) and unaffected controls from the same F1 background. The
      med(J) mutation results in greatly reduced levels of Scn8a voltage-gated sodium
      channels, which causes abnormal conduction of action potentials throughout the
      nervous system and may account for the virtual absence of spontaneous bursting
      activity in the dorsal cochlear nucleus. The med(J) mice also have tremors,
      display dystonic postures, and drag their hind legs. The mice were tested using a
      conditioned suppression/avoidance procedure, with minor modifications of the
      apparatus made to accommodate the motor-impaired med(J) mice. Thresholds were
      repeatedly obtained up to the age of 50 weeks to determine if the animals
      developed a hearing loss with age. The results indicate that med(J) mice have
      normal thresholds, with the first signs of hearing loss (detectable at 80 kHz)
      appearing for both the med(J) and normal mice by 48 weeks. Neither the med(J) nor
      the normal mice could hear below 1 kHz, indicating that house mice fall into the
      group of mammals with poor low-frequency hearing. The results also demonstrate
      that the conditioned suppression/avoidance procedure is well suited for assessing
      hearing in severely impaired, as well as normal, mice and that it can provide for
      the rapid determination of thresholds necessary to follow changes in hearing that
      may occur as the result of age, disease, mutation, or drugs.

PMID- 12204356
TI  - Imaging the intact guinea pig tympanic bulla by orthogonal-plane fluorescence
      optical sectioning microscopy.
AB  - Orthogonal-plane fluorescence optical sectioning (OPFOS) microscopy was developed
      for the purpose of making quantitative measurements of the intact mammalian
      cochlea and to facilitate 3D reconstructions of complex features. A new version
      of this imaging apparatus was built with a specimen chamber designed to
      accommodate samples as large as the intact guinea pig bulla. This method left the
      cochlear connections with the vestibular system and with the ossicles of the
      middle ear undisturbed, providing views within the cochlea with no breaches of
      its structural integrity. Since the features within the bulla were not physically
      touched during the preparation process, the risk of damage was minimized, and
      were imaged in relatively pristine condition with spatial resolution to 16
      microm. A description of the imaging method and specimen preparation procedure is
      presented, as are images of features from the cochlea, ossicles, and vestibular
      system.

PMID- 12204357
TI  - Changes in calcium-binding protein expression in the auditory brainstem nuclei of
      the jaundiced Gunn rat.
AB  - Sensorineural hearing loss and auditory dysfunction are major sequelae of
      neonatal hyperbilirubinemia. The sites and cellular effects of bilirubin toxicity
      in the auditory brainstem pathway are not easily detected. Since altered
      intracellular calcium homeostasis may play a role in neuronal cell death, we
      hypothesized that the expression of calcium-binding proteins may be altered in
      the classic animal model of bilirubin neurotoxicity. The expression of the
      calcium-binding proteins, calbindin-D28k and parvalbumin, in the brainstem
      auditory pathway of homozygous recessive jaundiced (jj) Gunn rats was examined by
      light and electron microscopic immunohistochemistry at 18 days postnatally and
      compared to the findings obtained from age-matched non-jaundiced heterozygous
      (Nj) littermate control rats. Immunoreactive staining for both calbindin and
      parvalbumin was reduced in the cochlear nuclei and the superior olivary complex
      in jj rats. The extent of the reduction in immunoreactivity was related to the
      severity of the clinical symptoms. By contrast, immunoreactive staining in other
      brainstem areas (e.g., dorsal and ventral nuclei of the lateral lemniscus,
      inferior colliculus), thalamic (medial geniculate body) auditory areas, and
      neighboring non-auditory structures was similar in jaundiced and control rats.
      Calbindin-immunoreactive staining in the superior paraolivary and medial superior
      olivary nuclei in Nj rats was associated with myelinated axons, whereas
      parvalbumin-immunoreactive staining was localized postsynaptically in neuronal
      somata and dendrites. Immunoreactive staining for the calcium-binding proteins
      calbindin and parvalbumin in lower brainstem auditory nuclei shows abnormalities
      in areas susceptible to the effects of hyperbilirubinemia and provides a
      sensitive new way to assess bilirubin toxicity in the auditory system.

PMID- 12204358
TI  - Behavioral investigation of some possible effects of the central olivocochlear
      pathways in transgenic mice.
AB  - This study investigated the auditory behaviors of transgenic mice with deletions
      of alpha9 nicotinic acetylcholine receptor subunits. In the normal mammalian
      cochlea, the mechanical properties of outer hair cells are modified by the
      release of acetylcholine from olivocochlear efferent terminals.
      Electrophysiological correlates of this efferent feedback have not been
      demonstrated in alpha9 knockout mice, presumably because they are mediated by
      alpha9 receptors. Previous studies have associated lesions of olivocochlear
      pathways with hearing impairments in background noise. The prediction that alpha9
      knockout mice would show similar deficits was tested by collecting psychophysical
      thresholds for tone detection and intensity discrimination from knockout mice,
      within-strain control subjects, and CBA/CaJ mice. Comparable performance was
      observed for the subject groups in quiet and in continuous background noise. The
      preservation of auditory function in alpha9 knockout mice suggests that central
      efferent pathways work in combination with the peripheral olivocochlear system to
      enhance hearing in noise, and may compensate for profound manipulations of
      peripheral feedback in highly routine testing procedures. An intriguing
      possibility is that these central mechanisms include the brainstem collaterals of
      olivocochlear neurons since their post-synaptic targets do not express alpha9
      receptors and therefore are likely to maintain their effects in alpha9 knockout
      mice.

PMID- 12204359
TI  - Onset and offset responses from inferior colliculus and auditory cortex to paired
      noisebursts: inner hair cell loss.
AB  - Thirteen adult chinchillas were anesthetized with ketamine/acepromazine and
      tungsten electrodes were placed in the right inferior colliculus (IC) and
      auditory cortex (AC). A reference electrode was implanted in the anterior
      cranium. Following a recovery period, AC and IC responses to left ear stimulation
      were obtained from unanesthetized animals resting in a passive restraint inside a
      sound-attenuating booth. After the first recording, the animals were injected
      with carboplatin (75 mg/kg). Four to five weeks later, a second recording was
      made. Stimuli were 50 ms duration (0 ms rise and fall time), 80 dB SPL noiseburst
      pairs. In one group of seven animals, the gap time varied from 1 to 64 ms. In a
      second group of six animals, the gap time ranged from 0.25 to 64 ms in order to
      determine gap threshold. The responses were amplified (10000x) and filtered from
      10 to 3000 Hz. Each response was the average of 100 stimulus presentations. The
      dependent variables were the latency of the initial positive peak and the
      amplitude of the response from initial positive peak to the following negativity.
      Following the second recording, all animals were sacrificed, the cochleas
      harvested, and cochleograms were obtained by counting outer hair cells (OHCs) and
      inner hair cells (IHCs). For the onset response to the second noiseburst of each
      pair, response amplitudes decreased and latencies increased with decreasing gap
      time. For a 64 ms gap time, the IC response approached the latencies and
      amplitudes seen for the onset response to the single noiseburst or first
      noiseburst in the pair (herein called "baseline" values), while the AC response
      latency approached baseline values, but AC amplitude did not. Interestingly, the
      offset responses to the first noiseburst were not present at gaps of less than 8
      ms, while the onset responses to the second noiseburst were typically present at
      gaps of 1-2 ms. Cochleograms revealed a normal (or near-normal) complement of
      OHCs, and IHC loss averaging roughly 30-40% in apical regions and increasing to
      60-70% in more basal regions (compared to normative data). Following carboplatin,
      the latencies of IC onset responses were delayed by several tenths of a
      millisecond, with the greatest pre- versus post-carboplatin latency shift
      occurring at short noiseburst gaps. AC response latencies were largely unaffected
      by carboplatin. IC onset response amplitudes were reduced following carboplatin,
      while AC onset responses were similar to pre-carboplatin values. IC offset
      response latencies to the first noiseburst were increased post-carboplatin, while
      AC offset response latencies varied little from pre-carboplatin values. IC and AC
      offset response amplitudes to the first noiseburst were decreased post
      carboplatin.

PMID- 12204360
TI  - Nitric oxide induces hyperpolarization by opening ATP-sensitive K(+) channels in
      guinea pig spiral modiolar artery.
AB  - Nitric oxide (NO) hyperpolarizes vascular smooth muscle cells and dilates blood
      vessels of various beds, but little is known on cochlear vasculatures. Using in
      vitro preparations of the spiral modiolar artery (SMA), intracellular electrical
      recording and labeling techniques, we found that the NO donor DPTA-NONOate (10
      microM) caused a hyperpolarization of approximately 9 mV in all the cells that
      had a low resting potential (RP) level near -40 mV. The hyperpolarization
      amplitude was concentration-dependent, with a 50% effect concentration (EC(50))
      of 1 microM. The responses occur in both smooth muscle and endothelial cells,
      neither of which was blocked by 18beta-glycyrrhetinic acid. The induced
      hyperpolarization was completely blocked by glipizide, but not by charybdotoxin,
      apamin, barium, 4-aminopyridine or tetraethylammonium. The hyperpolarizing
      responses were imitated by pinacidil (EC(50)=30 microM). The pinacidil-induced
      response was also blocked by glipizide but not by the other K(+) channel blockers
      mentioned above. Both DPTA-NONOate and pinacidil had little membrane potential
      effect on cells that had a high RP level near -75 mV. However, when the high RP
      cells were depolarized to a level beyond -45 mV by barium, both DPTA-NONOate and
      pinacidil hyperpolarized these cells not differently from those that initially
      had a low RP. It is concluded that NO hyperpolarizes the SMA primarily by
      activating K(ATP) channels in both muscle and endothelial cells.

PMID- 12204361
TI  - Heschl's gyrus is more sensitive to tone level than non-primary auditory cortex.
AB  - Previous neuroimaging studies generally demonstrate a growth in the cortical
      response with an increase in sound level. However, the details of the shape and
      topographic location of such growth remain largely unknown. One limiting
      methodological factor has been the relatively sparse sampling of sound
      intensities. Additionally, most studies have either analysed the entire auditory
      cortex without differentiating primary and non-primary regions or have limited
      their analyses to Heschl's gyrus (HG). Here, we characterise the pattern of
      responses to a 300-Hz tone presented in 6-dB steps from 42 to 96 dB sound
      pressure level as a function of its sound level, within three anatomically
      defined auditory areas; the primary area, on HG, and two non-primary areas,
      consisting of a small area lateral to the axis of HG (the anterior lateral area,
      ALA) and the posterior part of auditory cortex (the planum temporale, PT). Extent
      and magnitude of auditory activation increased non-linearly with sound level. In
      HG, the extent and magnitude were more sensitive to increasing level than in ALA
      and PT. Thus, HG appears to have a larger involvement in sound-level processing
      than does ALA or PT.

PMID- 12204362
TI  - Acoustically and electrically evoked responses of the human cortex before and
      after cochlear implantation.
AB  - Multi-channel auditory evoked potentials (AEP) were recorded before and after
      cochlear implantation (CI) from a patient suffering from severe high frequency
      hearing loss with residual, but highly fluctuating hearing around 250 Hz.
      Immediately after CI activation early components of the N1 were present. Later N1
      components developed during the use of CI. The unique result of this single case
      study is the concordance of the cortical AEP pattern obtained by native and
      artificial peripheral stimulation, which can be regarded as an indicator for the
      adequate function of the CI.

PMID- 12204363
TI  - An explanatory note.

PMID- 12204364
TI  - Evaluation of restriction fragment length polymorphism analysis of 16S rDNA as a
      tool for genomovar characterisation within the Burkholderia cepacia complex.
AB  - A total of 154 Burkholderia cepacia complex strains, isolated from cystic
      fibrosis and non-cystic fibrosis patients and the environment, representing all
      nine genomovars and a putative tenth, were analysed by 16S rDNA-restriction
      fragment length polymorphism using the restriction enzymes AluI, CfoI and DdeI.
      Examining this diverse strain collection resulted in very diverse restriction
      patterns. Only B. cepacia genomovar VI could be identified unambiguously. The
      same restriction patterns were observed for B. cepacia genomovars I and III and
      approximately half of the Burkholderia ambifaria, B. anthina and B. pyrrocinia
      strains. Burkholderia vietnamiensis and B. ubonensis, a putative tenth B. cepacia
      complex genomovar, shared identical restriction profiles. The majority of
      Burkholderia multivorans and B. stabilis isolates generated a unique restriction
      pattern, but two strains of each showed divergent restriction profiles which were
      also observed in other genomovars.

PMID- 12204365
TI  - Isolation and characterization of a reservosome fraction from Trypanosoma cruzi.
AB  - Reservosomes are acidic compartments present at the posterior region of
      epimastigote forms of Trypanosoma cruzi that store proteins and lipids. During
      metacyclogenesis, they consume their contents and disappear. Reservosomes are
      rich in cruzipain, the main proteolytic enzyme of this parasite. By
      centrifugation in a sucrose gradient, we have obtained a highly purified
      subcellular fraction containing reservosomes from 5-day-old Y strain
      epimastigotes. Transmission electron microscopy showed that the fraction
      contained well-preserved organelles. The protein profile of the organelle
      analyzed by SDS-PAGE depicted a wide range of protein bands, predominating those
      corresponding to a triplet of 60-51 kDa and a doublet of 25-23 kDa. Protease
      activity in substrate-containing gels, in the presence or absence of protease
      inhibitors, showed that cysteine proteinase is enriched and very active in the
      purified fraction. Enzymatic assays demonstrated the absence of pyrophosphatase,
      an acidocalcisome marker, and succinate cytochrome c reductase, a mitochondrial
      marker, although these enzymes were active in other regions of the purification
      sucrose gradient. Thin layer chromatographic neutral lipid analysis of purified
      reservosomes demonstrated that the organelle stores large amounts of ergosterol
      and esterified cholesterol. Phospholipid analysis indicated phosphatidylcholine
      and phosphatidylethanolamine as the major constituents of reservosome membranes.

PMID- 12204366
TI  - Development of a TaqMan quantitative PCR assay specific for Cryptosporidium
      parvum.
AB  - A rapid detection method that is both quantitative and specific for the water
      borne human parasite Cryptosporidium parvum is reported. Real-time polymerase
      chain reaction (PCR) combined with fluorescent TaqMan technology was used to
      develop this sensitive and accurate assay. The selected primer-probe set
      identified a 138-bp section specific to a C. parvum genomic DNA sequence. The
      method was optimized on a cloned section of the target DNA sequence, then
      evaluated on C. parvum oocyst dilutions. Quantification was accomplished by
      comparing the fluorescence signals obtained from test samples of C. parvum
      oocysts with those obtained from standard dilutions of C. parvum oocysts. This
      real-time PCR assay allowed reliable quantification of C. parvum oocysts over six
      orders of magnitude with a baseline sensitivity of six oocysts in 2 h.

PMID- 12204367
TI  - Detection of sialoglycomolecules in five plant trypanosomatids and in an insect
      phytophagous isolate.
AB  - The sialoglycoprotein profiles of five plant trypanosomatids (Phytomonas spp.)
      and of one flagellate (Herpetomonas sp.) isolated from the salivary gland of a
      phytophagous insect (Phthia picta) were analyzed by Western blotting using three
      distinct lectins (LFA, SNA and MAA), which recognize specifically sialic acid
      residues in glycoconjugates. All six flagellates presented at least one
      polypeptide recognized by the lectins, with the exception of Phytomonas francai,
      which did not show any reactivity with SNA agglutinin. Phytomonas serpens and P.
      francai showed the most distinct pattern of sialoglycoproteins. Phytomonas
      mcgheei, Herpetomonas sp. and the two other Phytomonas spp., isolated from latex,
      displayed an identical sialomolecule profile. We discuss the possible role of the
      sialoglycoproteins in the physiology of these trypanosomatids.

PMID- 12204368
TI  - The ycf27 genes from cyanobacteria and eukaryotic algae: distribution and
      implications for chloroplast evolution.
AB  - The two ycf27 genes from the filamentous cyanobacterium Tolypothrix PCC 7601 have
      been cloned and sequenced. These two genes, previously designated rpaA and rpaB,
      encode putative transcriptional regulators of the 'OmpR' family. In Synechocystis
      PCC 6803, homologous genes have been linked to the regulation of transfer of
      excitation energy from the phycobilisome to photosystem (PS) I and PSII
      respectively. Partial clones from Spirulina platensis, Dactylococcopsis salina
      and Synechococcus PCC 7002 have also been sequenced. A table of identity between
      the proteins confirms that RpaB belongs in the same family as the algal ycf27
      proteins. However, RpaA is a rather different protein and should lose the
      designation ycf27. The loss of rpaB from the plastid genomes of eukaryotic algae
      is associated with the loss of phycobiliproteins, so it is likely that this gene
      performs a similar role in algae to that in cyanobacteria. The implications for
      chloroplast evolution are discussed along with the possible identity of the
      cognate histidine kinase gene in the plastid genomes.

PMID- 12204369
TI  - Peroxisome deficiency represses the expression of n-alkane-inducible YlALK1
      encoding cytochrome P450ALK1 in Yarrowia lipolytica.
AB  - Among the eight genes (YlALK1-YlALK8) encoding P450 cytochromes of the CYP52
      family of the n-alkane-assimilating yeast Yarrowia lipolytica, Y1ALK1 is most
      highly induced by n-alkanes with short hydrocarbon chains, such as n-decane, and
      involved in the initial hydroxylation of n-alkane. To determine the factors
      regulating YlALK1 expression, we isolated an n-decane assimilation-deficient
      mutant, B0-6-1, whose YlALK1 expression level was lower than that of the wild
      type. By complementation of the mutation of B0-6-1, we cloned a gene having an
      open reading frame of 1062 bp. The putative gene product is a protein of 354
      amino acids and has significant homology to Pex10ps of other organisms. We named
      this gene YlPEX10. YlPex10p has a C(3)HC(4) ring finger motif common among
      Pex10ps in its C-terminal region. This motif was also essential for the function
      of YlPex10p. Both B0-6-1 and a null mutant of YlPEX10 failed to form peroxisome
      and showed low-level transcription of YlALK1 after the change of carbon source to
      n-decane. Furthermore, YlPEX5 and YlPEX6 disruptants also showed low-level
      transcription of YlALK1 like the YlPEX10 disruptant and B0-6-1 mutant. We propose
      that in this organism peroxisome deficiency represses the expression of n-alkane
      inducible YlALK1 encoding cytochrome P450ALK1.

PMID- 12204370
TI  - A multiplex-PCR for the differentiation of Mycobacterium bovis and Mycobacterium
      tuberculosis.
AB  - A multiplex-polymerase chain reaction (PCR) assay based on one-step amplification
      and detection of two different mycobacterial genomic fragments was designed for
      differentiation of Mycobacterium bovis and Mycobacterium tuberculosis. The
      oligonucleotide primers were chosen from a 500-bp genomic fragment which is well
      conserved in M. bovis and the pncA gene (based on M. tuberculosis-specific
      nucleotide polymorphism, a cytosine residue at position 169), specific for M.
      tuberculosis. The multiplex-PCR allowed detection of a single product of 500 bp
      in M. bovis isolates while M. tuberculosis isolates generated a single product of
      185 bp, with or without an additional product of 500 bp. None of the atypical
      mycobacterial isolates revealed any amplification products. The method was found
      to be highly specific and could detect as little as 20 pg of pure DNA. This
      multiplex-PCR assay, based on the 500-bp fragment and the pncA gene, may be very
      useful for the rapid and specific differentiation of these two closely related
      mycobacteria and easy to use in medical and veterinary microbiological
      laboratories.

PMID- 12204371
TI  - Monocyte chemotactic protein-1 secretion and expression after Toxoplasma gondii
      infection in vitro depend on the stage of the parasite.
AB  - Infection of human fibroblasts with tachyzoites of RH and Prugniaud strains, two
      different strains of Toxoplasma gondii, significantly increased monocyte
      chemotactic protein (MCP)-1 secretion contrary to what happened with bradyzoites
      of the cystogenetic strain. Quantification of MCP-1 mRNA by RT-PCR showed that
      this phenomenon is regulated at the transcriptional level. Thus, the stage of
      parasite can be deciding in MCP-1 induction since only tachyzoites induced MCP-1
      expression and secretion. MCP-1 induced by tachyzoites could be involved in cell
      recruitment, as shown by the quantification of MCP1 ARNm by real-time PCR
      (LightCycler, Roche Diagnostics), in the pathogenesis of T. gondii infection.

PMID- 12204372
TI  - Rapid and sensitive identification of pathogenic and apathogenic Bacillus
      anthracis by real-time PCR.
AB  - Bacillus anthracis spores have been shown to be an efficient biological weapon
      and their recent use in bioterrorist attacks has demonstrated the need for rapid
      and specific diagnostics. A TaqMan real-time PCR for identification of B.
      anthracis was developed, based on the two plasmids, pX01 and pX02, both of which
      are necessary for pathogenicity, as well as on the chromosomally encoded rpoB
      gene. Bacteria picked from colonies or pelleted from liquid cultures were
      directly inoculated into the PCR mix, thus avoiding time-consuming DNA
      preparation and minimizing handling risks. B. anthracis spores were cultivated
      for a few hours in enrichment broth before PCR analysis, or used directly for
      real-time PCR, thus allowing to confirm or exclude potential attacks
      approximately 2-3 h after the material has arrived in the laboratory.

PMID- 12204373
TI  - Chemical and physicochemical characterization of the sialic acid-specific lectin
      from Cepaea hortensis.
AB  - A sialic acid-specific lectin was isolated from the albumin glands of the garden
      snail Cepaea hortensis by affinity chromatography on fetuin-Sepharose following
      gel filtration on Superdex 200. The purified native lectin showed a molecular
      mass of about 95 kDa by gel filtration and 100 kDa by SDS electrophoresis. It was
      cleaved by boiling in buffer containing SDS in three serological identical bands
      corresponding to molecular masses of about 24, 20 and 16 kDa, respectively. From
      these three fragments, only the 24- and the 20-kDa bands were found to be
      glycosylated. Only the three sugars mannose, galactose and N-acetylglucosamine
      could be detected in a molar ratio of 3:8.6:2. The oligosaccharide moieties seem
      to be N- and partially O-glycosidic bound. Isoelectric focusing (IEF) of the
      purified lectin revealed a heterogeneous pattern with bands in the pH range of
      4.3-5.0. Isolated bands of different isoelectric points showed in SDS
      electrophoresis the same three fragments with molecular masses of 24, 20 or 16
      kDa. The heterogeneity of the lectin was revealed either by IEF or amino acid
      sequencing of internal tryptic peptides.

PMID- 12204374
TI  - Participation of DnaK in expression of genes involved in virulence of Listeria
      monocytogenes.
AB  - DnaK is required for adaptation to environmental stress and is also involved in
      bacterial growth under normal conditions. To examine whether DnaK plays a role in
      the expression of genes related to pathogenicity of Listeria monocytogenes, the
      transcription of flaA, iap and lmaA in a dnaK mutant was analyzed. Northern blot
      analysis showed that expression of flaA and lmaA mRNAs was reduced in the dnaK
      mutant, THY-LK1. A reporter assay revealed that transcription of lmaB in the dnaK
      mutant, LKS01, constructed in this study was lower than that in the parental
      strain. In contrast, the dnaK mutation had no effect on the transcription of iap.
      These results suggest that DnaK is involved in the transcription of flaA and
      lmaB.

PMID- 12204375
TI  - Identification, molecular cloning and expression of an alpha-N
      acetylgalactosaminidase gene from Clostridium perfringens.
AB  - The Clostridium perfringens gene encoding the previously characterized alpha-N
      acetylgalactosaminidase (alphaNAG) was identified by protein microsequencing and
      database searching. The alphaNAG protein, designated AagA, was found to be
      encoded by a hypothetical gene of unknown function in the recently completed
      genome sequence of C. perfringens strain 13. The deduced translation product of
      629 amino acid residues possessed a region of limited homology to several
      hypothetical open reading frames, an enterotoxin of unknown function and several
      known or predicted alpha-galactosidases, but did not exhibit homology to any of
      the multiple sequenced eukaryotic alphaNAG proteins. The C. perfringens aagA
      gene, encoding AagA, was cloned in an Escherichia coli T7 expression system,
      resulting in recombinants exhibiting high-level expression of the expected
      alphaNAG activity. To our knowledge, this is the first report of the cloning and
      expression of a bacterial alphaNAG-encoding gene and represents an important step
      in the development of recombinant alphaNAG as a tool in the enzymatic conversion
      of blood group antigens.

PMID- 12204376
TI  - Effect of p-nitrophenol metabolites on microbial cell electro-optical
      characteristics.
AB  - The effect of cellular p-nitrophenol (PNP) metabolism on the electro-optical (EO)
      characteristics of Pseudomonas putida C-11, P. putida BA-11, and Acinetobacter
      calcoaceticum A-122 was studied. When P. putida C-11 was incubated with
      hydroquinone, the orientational spectra of the cell suspensions changed
      considerably. When P. putida BA-11 and A. calcoaceticum A-122 were incubated with
      hydroquinone, no orientational spectrum changes were noted, possibly attesting to
      the operation of different PNP-metabolic pathways. In C-11, the initial
      metabolism of PNP may occur via the production of hydroquinone, an intermediate
      for PNP metabolism; in BA-11 and A. calcoaceticum A-122, via the production of 4
      nitropyrocatechin, followed by a rupture of the aromatic ring. The respiratory
      activity of the strains toward hydroquinone was investigated concurrently. The
      results suggest that EO analysis is a good candidate for the study of cellular
      metabolism.

PMID- 12204377
TI  - Use of a LightCycler gyrA mutation assay for identification of ciprofloxacin
      resistant Campylobacter coli.
AB  - A fluorescence resonance energy transfer-based assay has been employed to detect
      mutations at the 86 codon in the DNA gyrase A (gyrA) gene in Campylobacter coli
      strains. These mutations were associated with ciprofloxacin resistance in strains
      isolated in Italy in 2000. The mutations in the gyrA gene were detected by real
      time PCR amplification followed by hybridization with two fluorescent probes
      designed with sequences complementary to the wild-type C. coli gyrA gene.
      Mutation detection was performed by melting peak analysis of the probe-PCR
      product hybrid performed on a LightCycler (Roche Diagnostic). This gyrA mutation
      assay allows a rapid and reproducible screening method of ciprofloxacin-resistant
      C. coli strains.

PMID- 12204378
TI  - The filamentation pathway controlled by the Efg1 regulator protein is required
      for normal biofilm formation and development in Candida albicans.
AB  - Candida albicans biofilms are structured microbial communities composed of a
      mixture of yeast cells and hyphal elements, suggesting a pivotal role for the
      dimorphic switch in the development of biofilms. We have used C. albicans mutants
      defective in genes involved in filamentation (Deltacph1, Deltaefg1, Deltahst7,
      and Deltacst20) and compared these mutants to wild-type strains to determine
      whether filamentation is an integral factor for biofilm formation. Scanning
      electron microscopy revealed that Deltacph1, Deltahst7 and Deltacst20 mutants
      were able to filament and form structured biofilms displaying three-dimensional
      architecture similar to those formed by wild-type strains. However, Deltaefg1 and
      Deltacph1/Deltaefg1 mutants were unable to filament and did not form biofilms,
      but rather sparse monolayers of loosely attached elongated, rod-like, cells.
      Antimicrobial susceptibility testing showed intrinsic resistance of all mutant
      strains to fluconazole and amphotericin B when attached to the surface of
      biomaterials. These results suggest that hyphal formation is pivotal for biofilm
      development in C. albicans. However, the sessile lifestyle associated with
      adherent cells confers antifungal resistance, regardless of coherent biofilm
      formation.

PMID- 12204379
TI  - Identifying Pex21p as a protein that specifically interacts with yeast seryl-tRNA
      synthetase.
AB  - The interaction of Saccharomyces cerevisiae seryl-tRNA synthetase (SerRS) with
      peroxin Pex21p was identified in a two-hybrid screen with SerRS as bait. This was
      confirmed by an in vitro binding assay with truncated Pex21p fused to glutathione
      S-transferase. Furthermore, purified Pex21p acts as an activator of yeast seryl
      tRNA synthetase in aminoacylation in vitro, revealing the functional significance
      of the Pex21p-SerRS interaction. Pex21p is a protein involved in the peroxisome
      biogenesis [Purdue, P.E., Yang, X. and Lazarow, P.B., J. Cell Biol. 143 (1998)
      1859-1869]. Since eukaryotic aminoacyl-tRNA synthetases are known to participate
      in assembles with other synthetases and non-synthetase proteins, we propose that
      this unusual interaction reflects another function of the peroxin.

PMID- 12204380
TI  - Construction and physiological studies of hydrogenase depleted mutants of
      Desulfovibrio fructosovorans.
AB  - Desulfovibrio fructosovorans possesses two periplasmic hydrogenases (a nickel
      iron and an iron hydrogenase) and a cytoplasmic NADP-dependent hydrogenase. The
      hydAB genes encoding the periplasmic iron hydrogenase were replaced, in the wild
      type strain as well as in single mutants depleted of one of the other two
      hydrogenases, by the acc1 gene encoding resistance to gentamycin. Molecular
      characterization and remaining activity measurements of the resulting single and
      double mutants were performed. All mutated strains exhibited similar growth when
      H(2) was the electron donor but they grew differently on fructose, lactate or
      pyruvate as electron donors. Our results indicate that the loss of one enzyme
      might be compensated by another even though hydrogenases have different
      localization in the cells.

PMID- 12204381
TI  - Identification of the cellulose-binding and the cell wall-binding domains of
      Eubacterium cellulosolvens 5 cellulose-binding protein A (CBPA).
AB  - The cellulose-binding domain (CBD) and the cell wall-binding domain (CWBD) of
      Eubacterium cellulosolvens 5 cellulose-binding protein A (CBPA) have been
      determined. The gene (cbpA) encoding CBPA and its derivatives were expressed in
      Escherichia coli. We were able to obtain the eight recombinant proteins and
      examine for their cellulose-binding ability, cell wall-binding ability and
      carboxymethyl cellulase (CMCase) activity. Since five recombinant proteins, which
      contain the unknown domain (UD-2) located between two linker-like regions of
      CBPA, bound to cellulose, this region has been identified as the CBD. The CBD did
      not show a significant sequence similarity with any other CBDs. Moreover, the N
      terminal region of CBPA showed a significant sequence similarity with a catalytic
      domain of glycosyl hydrolase family 9, and the recombinant proteins containing
      the region showed CMCase activity. Since the UD-3, which is located in the C
      terminal region of CBPA, bound to the cell walls of E. cellulosolvens 5, the
      region has been identified as the CWBD. However, the CWBD did not show a
      significant sequence similarity with any other proteins previously reported.

PMID- 12204382
TI  - Taxonomic identity of type E botulinum toxin-producing Clostridium butyricum
      strains by sequencing of a short 16S rDNA region.
AB  - Several micro-organisms capable of producing botulinum neurotoxin type E, though
      phenotypically similar to Clostridium butyricum (a normally non-neurotoxigenic
      organism), have recently been isolated in Italy and China. Some of these micro
      organisms had been implicated in food-borne botulism, a serious neuroparalytic
      disease. The taxonomic identity of the type E botulinum toxin-producing strains
      is confirmed here, through sequencing of a genus- and species-specific segment of
      the 16S rRNA gene. Confirmation leads to the conclusion that neurotoxigenic C.
      butyricum must be regarded as an emergent food-borne pathogen.

PMID- 12204384
TI  - Transformation of cinoxacin by Beauveria bassiana.
AB  - The ability of the fungus Beauveria bassiana ATCC 7159 to transform the
      antibacterial agent cinoxacin was investigated. Cultures in sucrose-peptone broth
      were dosed with cinoxacin, grown for 20 days, and then extracted with ethyl
      acetate. Two metabolites were detected and purified by high-performance liquid
      chromatography. The major metabolite was identified by mass and proton nuclear
      magnetic resonance spectra as 1-ethyl-1,4-dihydro-3
      (hydroxymethyl)[1,3]dioxolo[4,5-g]cinnolin-4-one and the minor metabolite was
      identified as 1-ethyl-1,4-dihydro-6,7-dihydroxy-3-(hydroxymethyl)cinnolin-4-one.
      B. bassiana also reduced quinoline-3-carboxylic acid to 3
      (hydroxymethyl)quinoline.

PMID- 12204383
TI  - Biochemical and molecular characterization of the NAD(+)-dependent isocitrate
      dehydrogenase from the chemolithotroph Acidithiobacillus thiooxidans.
AB  - An isocitrate dehydrogenase (ICDH) with an unique coenzyme specificity from
      Acidithiobacillus thiooxidans was purified and characterized, and its gene was
      cloned. The native enzyme was homodimeric with a subunit of M(r) 45000 and showed
      a 78-fold preference for NAD(+) over NADP(+). The cloned ICDH gene (icd) was
      expressed in an icd-deficient strain of Escherichia coli EB106; the activity was
      found in the cell extract. The gene encodes a 429-amino acid polypeptide and is
      located between open reading frames encoding a putative aconitase gene (upstream
      of icd) and a putative succinyl-CoA synthase beta-subunit gene (downstream of
      icd). A. thiooxidans ICDH showed high sequence similarity to bacterial NADP(+)
      dependent ICDH rather than eukaryotic NAD(+)-dependent ICDH, but the NAD(+)
      preference of the enzyme was suggested due to residues conserved in the coenzyme
      binding site of the NAD(+)-dependent decarboxylating dehydrogenase.

PMID- 12204385
TI  - Purification and characterization of formate oxidase from a formaldehyde
      resistant fungus.
AB  - A formate oxidase activity was found in the crude extract of a formaldehyde
      resistant fungus isolated from soil. The fungus was classified and designated as
      Aspergillus nomius IRI013, which could grow on a medium containing up to 0.45%
      formaldehyde and consumed formaldehyde completely. The specific activity of
      formate oxidase in the extract of the fungus grown on formaldehyde was found to
      be considerably higher than that in the extracts of the fungus grown on formate
      and methanol. Formate oxidase from the fungus grown on formaldehyde was purified
      to homogeneity. The enzyme had a relative molecular mass of 100000 and was
      composed of two apparently identical subunits that had a relative molecular mass
      of 59000. The enzyme showed the highest activity using formate as substrate.
      Hydrogen peroxide was formed during the oxidation of formate. The Michaelis
      constant for formate was 15.9 mM; highest enzyme activity was found at pH 4.5
      5.0. The enzyme activity was strongly inhibited by NaN(3), p
      chloromercuribenzoate and HgCl(2).

PMID- 12204386
TI  - Update on caffeine consumption, disposition and action.
AB  - This report represents a current summary of the caffeine contents of various
      commercial products, and provides data on the spectrum of caffeine intake levels
      in man. A summary of the substance's pharmacokinetics describes information on
      its disposition in the body. The effects of caffeine are related to its
      interaction with adenosine receptors.

PMID- 12204387
TI  - Effects of caffeine on development and behavior in infancy and childhood: a
      review of the published literature.
AB  - The Medline literature on the behavioral effects of caffeine in infants and
      children are reviewed. There has been little recent work in this area. Generally,
      caffeine is well tolerated in usual dietary amounts, and there is evidence that
      individuals differ in their susceptibility to caffeine-related adverse effects,
      which in turn may influence their consumption. Overall, the effects of caffeine
      in children seem to be modest and typically innocuous.

PMID- 12204388
TI  - Effects of caffeine on human behavior.
AB  - The literature suggests that the following effects on behavior of adult humans
      may occur when individuals consume moderate amounts of caffeine. (1) Caffeine
      increases alertness and reduces fatigue. This may be especially important in low
      arousal situations (e.g. working at night). (2) Caffeine improves performance on
      vigilance tasks and simple tasks that require sustained response. Again, these
      effects are often clearest when alertness is reduced, although there is evidence
      that benefits may still occur when the person is unimpaired. (3) Effects on more
      complex tasks are difficult to assess and probably involve interactions between
      the caffeine and other variables which increase alertness (e.g. personality and
      time of day). (4) In contrast to the effects of caffeine consumption, withdrawal
      of caffeine has few effects on performance. There is often an increase in
      negative mood following withdrawal of caffeine, but such effects may largely
      reflect the expectancies of the volunteers and the failure to conduct "blind"
      studies. (5) Regular caffeine usage appears to be beneficial, with higher users
      having better mental functioning. (6) Most people are very good at controlling
      their caffeine consumption to maximise the above positive effects. For example,
      the pattern of consumption over the day shows that caffeine is often consumed to
      increase alertness. Indeed, many people do not consume much caffeine later in the
      day since it is important not to be alert when one goes to sleep. In contrast to
      effects found from normal caffeine intake, there are reports that have
      demonstrated negative effects when very large amounts are given or sensitive
      groups (e.g. patients with anxiety disorders) were studied. In this context
      caffeine has been shown to increase anxiety and impair sleep. There is also some
      evidence that fine motor control may be impaired as a function of the increase in
      anxiety. Overall, the global picture that emerges depends on whether one focuses
      on effects that are likely to be present when caffeine is consumed in moderation
      by the majority of the population or on the effects found in extreme conditions.
      The evidence clearly shows that levels of caffeine consumed by most people have
      largely positive effects on behavior. Excessive consumption can lead to problems,
      especially in sensitive individuals.

PMID- 12204389
TI  - Caffeine: behavioral effects of withdrawal and related issues.
AB  - Acquired tolerance to some behavioral effects of caffeine in humans is widely
      assumed to occur but is poorly documented and appears, at most, to be of low
      magnitude. Withdrawal from regular consumption of caffeine has been reported to
      result in a variety of symptoms, including: irritability, sleepiness, dysphoria,
      delerium, nausea, vomiting, rhinorrhea, nervousness, restlessness, anxiety,
      muscle tension, muscle pains and flushed face. Some of these same symptoms have
      been reported following excess intake of caffeine. The prevalence of symptoms
      reported on withdrawal in different studies also covers a wide range from 11% or
      less to 100%. It is suggested that the evidence leads to the conclusion that non
      pharmacological factors related to knowledge and expectation are the prime
      determinants of symptoms and their reported prevalence on withdrawal of caffeine
      after regular consumption.

PMID- 12204390
TI  - Effects of caffeine on bone and the calcium economy.
AB  - Caffeine-containing beverage consumption has been reported to be associated with
      reduced bone mass and increased fracture risk in some, but not most,
      observational studies. Human physiological studies and controlled balance studies
      show a clear but only a very small depressant effect of caffeine itself on
      intestinal calcium absorption, and no effect on total 24-h urinary calcium
      excretion. The epidemiologic studies showing a negative effect may be explained
      in part by an inverse relationship between consumption of milk and caffeine
      containing beverages. Low calcium intake is clearly linked to skeletal fragility,
      and it is likely that a high caffeine intake is often a marker for a low calcium
      intake. The negative effect of caffeine on calcium absorption is small enough to
      be fully offset by as little as 1-2 tablespoons of milk. All of the observations
      implicating caffeine-containing beverages as a risk factor for osteoporosis have
      been made in populations consuming substantially less than optimal calcium
      intakes. There is no evidence that caffeine has any harmful effect on bone status
      or on the calcium economy in individuals who ingest the currently recommended
      daily allowances of calcium.

PMID- 12204391
TI  - A review of the literature relating caffeine consumption by women to their risk
      of reproductive hazards.
AB  - From this detailed review of the literature, several conclusions can be drawn:
      (a) An association between caffeine consumption and a reproductive hazard is more
      likely to be seen in lower-quality studies than in studies that come closer to
      approximating the ideal. This is especially evident for "lower" birthweight and
      congenital anomalies. (b) The association between caffeine consumption and
      spontaneous abortion may well reflect the Stein-Susser epiphenomenon (women with
      prominent nausea tend to reduce caffeine consumption and nausea appears to be a
      marker of good implantation, perhaps reflecting a favorable balance of hormones
      produced by a healthy placenta). (c) The claim that caffeine consumption by women
      delays conception has not been followed by convincing support. (d) Reproductive
      hazards associated with cigarette smoking tend to be associated with
      caffeine/coffee consumption. Sometimes this appears to be a consequence of
      residual confounding associated with inadequate adjustment for cigarette smoking,
      which is over-represented among those who drink the most coffee/caffeine.
      Sometimes this reflects the tendency of women to underreport socially undesirable
      behaviors (e.g. smoking) while accurately reporting socially neutral behaviors
      (e.g. coffee and caffeine consumption). Thus, it seems reasonable to conclude
      that no convincing evidence has been presented to show that caffeine consumption
      increases the risk of any reproductive adversity.

PMID- 12204392
TI  - Plasma and in vitro levels of cytokines during and after a Plasmodium falciparum
      malaria attack in Gabon.
AB  - Fifty subjects living in a malaria endemic area were studied at diagnosis of a
      Plasmodium falciparum attack and 3 weeks later. Absolute numbers of CD3(+),
      CD4(+) and CD8(+) lymphocytes as well as plasma cytokines and secreted cytokines
      after in vitro mitogenic stimulation were measured. At enrollment, lymphopenia
      was observed, lending support to the reallocation hypothesis during the acute
      phase. A significant elevation of the number of CD8(+) cells was present in the
      peripheral blood during the recovery phase. During the acute phase, plasma IL-6
      levels peaked while in vitro production capacity was high at both phases. Plasma
      IL-6 concentrations were positively related to blood parasite density at D0, as
      IL-4 and IFN-gamma, suggesting an early intervention of these cytokines. Plasma
      IL-2 levels were low at diagnosis although cells retained their ability to
      produce IL-2, which was found more frequently in plasma after cure. Acquisition
      of immunity with age was in relation with greater secretion abilities of cells
      for type 1 and type 2 cytokines during the parasite clearance phase. We conclude
      to an early implication of type 2 cytokines and IFN-gamma, with particularly high
      levels of IL-6.

PMID- 12204393
TI  - Role of macrophage inflammatory protein-1alpha (MIP-1alpha) in macrophage homing
      in the spleen and heart pathology during experimental infection with Trypanosoma
      cruzi.
AB  - We investigated in vivo the effect of macrophage inflammatory protein-1alpha (MIP
      1alpha) inhibition upon the cellular recruitment into tissue damage sites and
      spleen histology in mice acutely infected with Trypanosoma cruzi.
      Histopathological studies of spleen sections revealed a 68% decrease in
      macrophage/monocyte infiltration as a result of MIP-1alpha neutralisation.
      Moreover, a reduction in the number of plasma cells and immunoblasts was
      observed. However, antibody (Ab)-mediated blocking of MIP-1alpha failed to modify
      tissue parasite levels. Examination of myocardial sections showed an increase in
      inflammatory lesions in mice treated with anti-MIP-1alpha Ab. There was also an
      increasing trend in the number of amastigote nests in the myocardium of anti-MIP
      1alpha-treated mice compared with controls. Administration of anti-MIP-1alpha Ab
      failed to affect either the extent of inflammatory infiltrates or the parasite
      count in liver and skeletal muscle. To the best of our knowledge, these data are
      the first in vivo demonstration that Cz.sbnd;C chemokine MIP-1alpha is involved
      in cellular recruitment during acute infection with T. cruzi, indicating that MIP
      1alpha influences macrophage/monocyte influx into target organs.

PMID- 12204394
TI  - Progress in control of cystic echinococcosis in La Rioja, Spain: decline in
      infection prevalences in human and animal hosts and economic costs and benefits.
AB  - The Autonomous Community of La Rioja is a region in the north of Spain where the
      mean annual number of surgical cases of cystic echinococcosis (CE) was 50 (19 per
      100000 inhabitants) during the years 1984-1987. This high clinical incidence
      prompted local authorities to implement a control program in 1986, whose methods
      and results are reported here. Initially, the program consisted in documenting
      the prevalence of CE in sheep and humans, communicating an awareness of the
      disease risks among the population, and treating all registered dogs with
      praziquantel at intervals of 45 days. Stray dogs were collected systematically,
      euthanized, and their intestines were examined for Echinococcus granulosus
      infection. Epidemiological data collected during the course of the program
      demonstrated that the major reservoirs of E. granulosus were the stray dogs,
      precisely the ones not receiving periodic praziquantel treatment. Therefore, the
      program emphasis was shifted to targeting critical points in the transmission of
      E. granulosus, including improved control of stray dogs, echinococcidal
      treatments of working sheep dogs, providing means for safe disposal of
      slaughtered sheep offal and safe disposal of dead sheep in sanitary pits. These
      measures led to a decline in prevalence of E. granulosus in dogs from 7.0% at the
      beginning of the program to 0.2% in 2000, i.e. a reduction of 97.2%. Prevalence
      of infection in adult sheep declined from 82.3 to 20.3%, i.e. a reduction of
      75.4%, while the mean number of cysts per infected animal decreased from 6.5% to
      0.58 (91% reduction). The rate of diagnoses of new cases in humans between these
      two dates dropped by 78.9%, from 19 to 4 per 100000 population. In terms of
      economic costs, these reductions were estimated to yield an increasing cumulative
      cost/benefit balance that was already positive on year 8 of the program (1994),
      and that reached 1.96 in year 2000.

PMID- 12204395
TI  - Ascaris lumbricoides among children in rural communities in the Northern Area,
      Pakistan: prevalence, intensity, and associated socio-cultural and behavioral
      risk factors.
AB  - The prevalence and intensity of Ascaris lumbricoides in 492 children from five
      rural villages in the Northern Area of Pakistan was examined. The overall
      prevalence of A. lumbricoides was 91% (95%CI 88.6-93.6) with geometric mean (GM)
      egg count intensities of 3985 eggs per g (epg). The most intense A. lumbricoides
      infections were found in children aged 5-8 years. We also investigated selected
      socio-cultural and behavioral variables for A. lumbricoides infections that might
      be relevant for the design of appropriate prevention and control programs.
      Univariate analysis associated A. lumbricoides intensity with age (P=0.004),
      location of household (P<0.01), defecation practices (P=0.02), soil eating habit
      (P<0.01), hand washing after defecation (P<0.01), and living with children under
      5 years old (P=0.02). Multivariate analysis identified the children's age 5-8
      (P<0.01), location of household in Surngo, Askole, and Stakchun where the pilot
      health care model activities were not done (P<0.01), and living with children
      under 5 years old (P=0.03) as variables statistically associated with the
      intensity of A. lumbricoides. The results indicated that there were certain clear
      risk factors in A. lumbricoides transmission, and that its intensity was
      influenced by age-related behavioral and environmental factors that contribute to
      exposure.

PMID- 12204396
TI  - Occurrence of a sibling species complex within neotropical lymnaeids, snail
      intermediate hosts of fascioliasis.
AB  - The delimitation of cryptic species within the genus Lymnaea, which are the main
      vectors of fascioliasis, remains a topic of controversy. An analysis of genetic
      variability based on 12 enzyme loci revealed different fixed alleles at 9 loci
      between two sympatric samples of Lymnaea viatrix at the type locality in Lima,
      Peru. The absence of heterozygotes within this locality indicates the presence of
      isolated populations or cryptic species within L. viatrix. Significant genetic
      differences were also found between these two L. viatrix samples from Lima and
      other populations of L. viatrix in South America and in addition to species such
      as L. truncatula, L. cubensis and L. columella. Moreover, the lack of variability
      within each Lymnaea samples studied indicates the existence of a high selfing
      rate in each species.

PMID- 12204397
TI  - Efficacy of a floating sustained release formulation of Bacillus thuringiensis
      ssp. israelensis in controlling Culex quinquefasciatus larvae in polluted water
      habitats.
AB  - Larvicidal efficacy and residual activity of a floating sustained release
      formulation of Bacillus thuringiensis ssp. israelensis (Bti) was tested in
      polluted water habitats against Culex quinquefasciatus, the vector of bancroftian
      filariasis, breeding in cesspools and cesspits. A total of 25 habitats having 65
      m(2) water surface area with C. quinquefasciatus immatures were treated with the
      formulation at the rate of 15 kg/ha. For comparison, in another area, 18 habitats
      with a water surface area of 70 m(2) were kept untreated. Evaluation was
      continued up to 179 days with three rounds of Bti application. The mean number of
      egg rafts did not differ significantly between treated and untreated habitats
      during the trial period indicating same level of recruitment. However, abundance
      of larvae and pupae was significantly lower in Bti treated habitats compared to
      that in untreated ones. The activity of the formulation, with 2 weeks delay in
      onset compared to treatment, caused >80% reduction in pupal abundance for a
      period of 30-34 days. Considering this, it is suggested that monthly application
      of Bti formulation will considerably reduce the recruitment of pupae of C.
      quinquefasciatus.

PMID- 12204398
TI  - First evidence of transmission of Leishmania (Viannia) lainsoni in a Sub Andean
      region of Bolivia.
AB  - Using ubiquitous primers which amplify the variable parts of kDNA minicircle of
      all Leishmania spp, we obtained for Leishmania (viannia) lainsoni a major band of
      605 bp (band 1) shared with L. V. braziliensis and a minor 524 bp band (band 2)
      specific of L. V. lainsoni. The specificity of the two bands was examined through
      Southern blot hybridization of kDNA PCR obtained from reference strains belonging
      to L. braziliensis, L. mexicana, L. donovani complexes with L. V. lainsoni
      species. Band 1 was not specific of L. V. lainsoni since it hybridized with some
      isolates belonging to L. braziliensis complex. In contrast, band 2 was L. V.
      lainsoni specific. PCR-based detection followed by hybridization with the new L.
      V. lainsoni probe (Band 2) and L. V. braziliensis probe (564 bp), was assayed
      using sample from a pool of 25 females of Lutzomiya nuneztovari anglesi, blood,
      skin and liver samples of 18 mammals, spinal cords of four mammals and blood and
      cutaneous ulcers aspirates from 95 patents from Sub Andean region of La Paz,
      Bolivia. We observed a ositive hybridization of four patients lesions and the
      pool of L. nuneztovari anglesi with the L. V. lainsoni probe. It is the first
      time that L. V. lainsoni is observed in a cycle of transmission in Bolivia. PCR
      products of three patients lesions and the pool of L. nuneztovari anglesi were
      also hybridized with the specific probe of L. V. braziliensis suggesting mixed
      infection in this focus.

PMID- 12204399
TI  - High prevalence of tungiasis in a poor neighbourhood in Fortaleza, Northeast
      Brazil.
AB  - Tungiasis has been reported to occur in many Latin American, Caribbean and
      African countries. However, epidemiological data are still very scanty and do not
      exist at all for Brazil. To fill this gap, a cross-sectional study has been
      undertaken in a shantytown (favela) in Fortaleza, Ceara State, northeast Brazil.
      All 327 households of a circumscribed sub-area were visited, and 1185 out of the
      1460 household members were thoroughly examined for the presence of tungiasis.
      Thirty-four% (95% CI: 30.9-36.4) were found to be infected with Tunga penetrans
      with a significant preponderance of the male sex (p<0.0001). In the children five
      to nine years old, the age group most heavily affected, the prevalence rate was
      65.4% (95% CI: 54.0-75.7) in boys and in 48.3% (95% CI: 37.4-59.2) in girls. The
      data show that tungiasis is hyper-endemic in the study area. As the favela is
      typical for the many poor communities in northeast Brazil, it can be assumed that
      tungiasis is a frequent infection in the underprivileged in this part of the
      country.

PMID- 12204400
TI  - Nonvascular abdominal interventional procedures.

PMID- 12204401
TI  - Percutaneous radiologic gastrostomy.
AB  - Gastrostomy is a preferred method of nutrition in patients with impaired ability
      to eat. Although surgical gastrostomy is a well-established method and has been
      widely performed in the last century, beginning with early 1980s, percutaneous
      gastrostomy techniques, either endoscopic or radiologic, has widely gained
      acceptance. As percutaneous methods have been shown to be an effective, safe,
      easy to perform and low-cost techniques with low morbidity and mortality rates,
      nowadays percutaneous gastrostomy is the first method of choice in need of
      nutrition in patients with functioning gut. In this article authors review the
      technique of percutaneous radiologic gastrostomy, as well as indications,
      contraindications, variations of technique, ethical considerations, controversies
      and comparison with surgical and endoscopic methods.

PMID- 12204402
TI  - Palliative treatment of inoperable malignant esophageal strictures with metal
      stents: one center's experience with four different stents.
AB  - PURPOSE: Our center's experience with Ultraflex, Flamingo, SR stent and Flexstent
      for the palliation of malignant esophageal strictures is reported, and current
      pertinent literature is reviewed. MATERIAL AND METHODS: Stents have been placed
      under fluoroscopic guidance between August 1993 and February 2002 for the
      palliation of malignant dysphagia in 116 patients. 59 patients received
      Ultraflex, 33 patients received Flamingo Wallstent, 20 patients received the SR
      stent and four patients received Flexstent. RESULTS: Stent placement was
      successful in all the patients, with good symptomatic control in 123 out of 126
      patients (98%) and no procedure-related complications. Four esophagorespiratory
      fistulas were successfully closed with covered Flamingo stents. Repeat
      intervention was necessary in 30 patients (51%) who received the Ultraflex stent,
      secondary to tumor ingrowth, overgrowth, ulceration, fistula and incomplete
      expansion. Two patients (6%) who received Flamingo Wallstent died due to
      gastrointestinal bleeding and one patient had proximal migration. Four patients
      (20%) who received the SR stent had complete migration of the stent. CONCLUSION:
      Covered stents were found to provide better long-term palliation compared to
      uncovered stents. The covered Flamingo Wallstent seems to be the best choice of
      stent for lesions where crossing the esophagogastric junction is not necessary.
      For lesions where it is mandatory to cross the junction it may be preferable to
      use a stent with an antireflux mechanism.

PMID- 12204403
TI  - Percutaneous drainage of abdominal abcess.
AB  - The mortality in undrained abdominal abscesses is high with a mortality rate
      ranging between 45 and 100%. The outcome in abdominal abscesses, however, has
      improved due to advances in image guided percutaneous interventional techniques.
      The main indications for the catheter drainage include treatment or palliation of
      sepsis associated with an infected fluid collection, and alleviation of the
      symptoms that may be caused by fluid collections by virtue of their size, like
      pancreatic pseudocele or lymphocele. The single liver abscesses may be drained
      with ultrasound guidance only, whereas the multiple abscesses usually require
      computed tomography (CT) guidance and placement of multiple catheters. The
      pancreatic abscesses are generally drained routinely and urgently. Non-infected
      pancreatic pseudocysts may be simply observed unless they are symptomatic or
      cause problems such as pain or obstruction of the biliary or the gastrointestinal
      tract. Percutaneous routes that have been described to drain pelvic abscesses
      include transrectal or transvaginal approach with sonographic guidance, a
      transgluteal, paracoccygeal-infragluteal, or perineal approach through the
      greater sciatic foramen with CT guidance. Both the renal and the perirenal
      abscesses are amenable to percutaneous drainage. Percutaneous drainage provides
      an effective and safe alternative to more invasive surgical drainage in most
      patients with psoas abscesses as well.

PMID- 12204404
TI  - Interventional radiological treatment in complications of pancreatitis.
AB  - Percutaneous interventional therapy plays an important role in treating
      complications of acute and chronic pancreatitis. With the development of cross
      sectional imaging and advanced interventional techniques, percutaneous drainage
      has become the preferred treatment for pancreatic fluid collections such as acute
      collections, pseudocysts and abscesses. Abscess and pancreatic hemorrhage are the
      most life threatening complications of pancreatitis. Massive hemorrhage is rare
      but frequently lethal. As a rule, bleeding complications of pancreatitis require
      prompt diagnosis and an aggressive surgical approach. In unstable patients with a
      severely bleeding pseudoaneurysm, hemostasis can be obtained by occlusion with
      mechanical devices.

PMID- 12204405
TI  - Percutaneous cholecystostomy.
AB  - Percutaneous cholecystostomy (PC), a technique that consists of percutaneous
      catheter placement in the gallbladder lumen under imaging guidance, has become an
      alternative to surgical cholecystostomy in recent years. Indications of PC
      include calculous or acalculous cholecystitis, cholangitis, biliary obstruction
      and opacification of biliary ducts. It also provides a potential route for stone
      dissolution therapy and stone extraction. Under aseptic conditions and ultrasound
      guidance, using local anesthesia, the procedure is carried out by using either
      modified Seldinger technique or trocar technique. Transhepatic or transperitoneal
      puncture can be performed as an access route. Several days after the procedure
      transcatheter cholangiography is performed to assess the patency of cystic duct,
      presence of gallstones and catheter position. The tract is considered mature in
      the absence of leakage to the peritoneal cavity, subhepatic, subcapsular, or
      subdiaphragmatic spaces. Response rates to PC in the literature are between the
      range of 56-100% as the variation of different patient population. Complications
      associated with PC usually occur immediately or within days and include
      haemorrhage, vagal reactions, sepsis, bile peritonitis, pneumothorax, perforation
      of the intestinal loop, secondary infection or colonisation of the gallbladder
      and catheter dislodgment. Late complications have been reported as catheter
      dislodgment and recurrent cholecystitis. PC under ultrasonographic guidance is a
      cost-effective, easy to perform and reliable procedure with low complication and
      high success rates for critically ill patients with acute cholecystitis. It is
      generally followed by elective cholecystectomy, if possible. However, it may be
      definitive treatment, especially in acalculous cholecystitis.

PMID- 12204406
TI  - Percutaneous management of bile duct stones.
AB  - This article presents a review of the interventional radiological procedures in
      the percutaneous management of the bile duct stones through T-tube or
      transhepatic tracts. Interventional stone removal techniques mainly include
      extraction through the T-tube tract with baskets or forceps and expulsion into
      the duodenum by means of baskets or balloon catheters with the dilatation of the
      sphincter of Oddi. Fragmentation or size reduction of the stone, dilatation of
      the strictures and cholangioscopic assistance can facilitate the procedures.

PMID- 12204407
TI  - Male breast disease: clinical, mammographic, and ultrasonographic features.
AB  - PURPOSE: To describe and quantitate the radiological (mammographic and
      ultrasonographic) characteristics of male breast disease and to report the
      clinical and pathological findings. MATERIALS AND METHODS: Two-hundred-thirty-six
      male patients with different male breast diseases, diagnosed at our institution
      between January 1990 and July 2001, were retrospectively evaluated. The history,
      physical examination, mammographic and ultrasonographic findings were analyzed.
      RESULTS: The spectrum of the disease in 236 male patients were gynecomastia
      (n=206), primary breast carcinoma (n=14), fat necrosis (n=5), lipoma (n=3),
      subareolar abscess (n=2), epidermal inclusion cyst (n=1), sebaceous cyst (n=1),
      hematoma (n=1), myeloma (n=1), and metastatic carcinoma (n=2). The distribution
      of patterns of gynecomastia were; 34% (n=71) nodular, 35% (n=73) dendritic and
      31% (n=62) diffuse glandular. Gynecomastia was unilateral in 55% (n=113) and
      bilateral in 45% (n=93) of the patients. Male breast cancer presented as a mass
      without microcalcifications in 86% (n=12) and with microcalcifications in 7%
      (n=1) of patients. The mass was obscured by gynecomastia, partially in two,
      totally in one patient. The location of the mass was retroareolar in 46% (n=6)
      and eccentric to the nipple in 54% (n=7) of patients. On ultrasonography (US),
      the contours were well-circumscribed in 20% (n=3) and irregular in 80% (n=12) of
      the masses. CONCLUSION: Male breast has a wide spectrum of diseases, some of
      which have characteristic radiological appearances that can be correlated with
      their pathologic diagnosis. In the evaluation of the male breast, mammography and
      US are essential and should be performed along with physical examination.

PMID- 12204408
TI  - Comparative diagnostic value and therapeutic relevance of magnetic resonance
      imaging and bone marrow scintigraphy in patients with metastatic solid tumors of
      the axial skeleton.
AB  - PURPOSE: To evaluate the comparative impact of magnetic resonance imaging (MRI)
      and bone marrow scintigraphy (BMS) in bone marrow metastases of solid tumors.
      METHODS: In 20 patients with solid tumors MRI of the axial skeleton and whole
      body BMS were retrospectively reviewed. Detectability of metastases, extent of
      disease and therapeutic implications were assessed. RESULTS: In 15/20 (75%)
      patients MRI and BMS concordantly revealed bone marrow metastases of the axial
      skeleton. In nine of these 15 patients (60%) MRI showed more metastases. Local
      radiotherapy or surgery was performed in seven of these cases (78%). BMS detected
      additional metastases of the appendicular skeleton in 8/15 (53%) patients. In
      4/20 cases (20%) the imaging findings were discordant. In three patients with
      degenerative changes (n=2) or lipoma (n=1) BMS was false positive. In another
      patient BMS failed to detect metastases proven by MRI and clinical follow-up
      resulting in subsequent radiation therapy. One patient had normal bone marrow.
      CONCLUSION: MRI appears to be more sensitive and specific in the detection of
      bone marrow metastases in the axial skeleton and is of clinical importance for
      subsequent local therapy.

PMID- 12204412
TI  - Method for one-step preparation of double-stranded DNA template applicable for
      use with Pyrosequencing technology.
AB  - A new one-step method for fast and efficient preparation of double-stranded DNA
      template, suitable for use with Pyrosequencing technology, has been developed. In
      the new method, two different types of oligonucleotides were used to prevent
      reannealing of remaining PCR primers to the template: oligonucleotides
      complementary to the PCR primers and 3'-end modified oligonucleotides with the
      same sequence as the PCR primers. Advantages with the new strategy are: (i)
      faster and simpler template preparation procedure (one-step); (ii) no need for
      exonuclease I treatment; and (iii) less problem with unspecific priming from loop
      structures and dimers. By careful oligonucleotide design, and/or by addition of
      single-stranded DNA-binding protein, problems with unspecific sequence signals
      due to mispriming can be reduced. The new method was used for analysis of
      genotype variations within the renin-angiotensin-aldosterone system.

PMID- 12204413
TI  - Preservation and analysis of nonequilibrium solute concentration distributions
      within mechanically compressed cartilage explants.
AB  - Solute transport within articular cartilage is of central importance to tissue
      physiology, and may mediate effects of mechanical compression on cell metabolism.
      We therefore developed and applied a freeze-substitution method for fixation of
      cartilage explant disks which had been compressed axially during radial solute
      desorption. Dextrans were used as model solutes. Explant morphology was well
      preserved and nonequilibrium solute concentration distributions were stable for
      several hours at room temperature. For desorption from explants compressed
      statically to 0-46% strain, analysis of laser confocal images and comparison to a
      theoretical model permitted measurement of effective diffusivities. Results were
      consistent with previous studies suggesting a role for transport limitations in
      mediating the decreases of chondrocyte metabolic rates associated with static
      compression. In explants compressed dynamically (23+/-5% strain at 0.001 Hz),
      evidence was obtained for the augmentation of effective transport rate of 3 kDa
      dextrans by oscillatory interstitial fluid flows. This suggests that augmented
      solute transport may play a role in mediating the increases of chondrocyte
      metabolic rates associated with dynamic compression. Methods appear suitable for
      quantitative studies of transport within mechanically compressed cartilage-like
      tissues, and may be valuable for identification of loading environments which
      optimize solute transport in tissue engineering applications.

PMID- 12204414
TI  - Novel approach for the effective determination of DNA scission site using the
      Sanger method.
AB  - This paper describes the effective determination of DNA scission site using a
      novel approach that is based on the Sanger method of nucleotide sequencing. The
      DNA scission site is determined by contrast with the nucleotide sequence of the
      DNA. Here, instead of the traditional Maxam-Gilbert method for the determination
      of the DNA sequence, we utilized the Sanger method and studied its effectiveness
      in the determination of DNA scission sites. Using this method, the determination
      of DNA scission site becomes more facile and exact. And the total time for the
      determination is reduced nearly by half in comparison to the Maxam-Gilbert
      method. Further advantages of this novel approach include the reduced risks of
      radiation exposure for researchers and contamination of the apparatus.

PMID- 12204415
TI  - An ELISA method to quantify the mannose 6-phosphate receptors.
AB  - Mannose 6-phosphate receptor proteins mediate transport of lysosomal enzymes to
      lysosomes in eukaryotes. Two receptors designated as MPR 300 and MPR 46 based on
      their apparent molecular mass have been well studied from human and bovine liver.
      In humans, it has been shown that the receptors are present in different
      concentrations in different tissues. In the present study, MPR 300 and MPR 46
      were purified from goat liver by phosphomannan affinity chromatography, and
      polyclonal antibodies were raised in rabbits. MPR 300 receptor specific
      antibodies have been purified from the antiserum using a goat-MPR 300-receptor
      gel. Using this affinity-purified antibody and the antiserum to goat MPR 46, as
      well as an affinity-purified MSC1 antibody that is specific for MPR 46, we
      developed an ELISA method to quantify both the receptors. The receptors could be
      measured in the concentration range of 1-10 ng using ELISA. The receptors could
      be quantified from membrane extracts of different tissues of goat and chicken
      using this method.

PMID- 12204416
TI  - Inclusional complex study between 6-p-toluidinylnaphthalene-2-sulfonate and 2
      hydroxypropyl-beta-cyclodextrin.
AB  - 6-p-Toluidinylnaphthalene-2-sulfonate (TNS) is used as a fluorescent probe for
      exploring hydrophobic regions of several biological substances, such as proteins,
      and studying solution state folding behaviour. The current study examines the
      complexation of TNS with 2-hydroxypropyl-beta-cyclodextrin (HPbetaCD) in aqueous
      solution, mainly by ultraviolet spectrophotometry using various concentrations of
      HPbetaCD. The structure of HPbetaCD was confirmed by using positive-ion
      electrospray ionization (ESI+) mass spectrometry. The complex was examined for
      its stoichiometry applying the continuous variation (Job plot) method. Also, the
      kinetics of the complex formation was monitored and the determination of the
      stability constant was calculated. For this purpose, the spectrophotometric
      properties of TNS were observed in the presence of increasing concentrations of
      HPbetaCD applying the transformed Benesi-Hildebrand linear model as well as a
      nonlinear one. The results suggest that TNS forms a stable complex of 1:1 molar
      ratio, at least at the examined concentrations. Furthermore, from the
      measurements of 1H nuclear magnetic resonance (1H NMR) spectra, interactions
      between protons of TNS with HPbetaCD were determined.

PMID- 12204417
TI  - Ligand-receptor interaction. Klotz-Hunston problem for two classes of binding
      sites and its solution.
AB  - The problem of the affinity and quantity determination of two classes of binding
      sites for ligand-receptor interaction using either Scatchard or Klotz plots was
      considered. Klotz and Hunston previously solved this problem only for the case of
      a representation of experimental data using the Scatchard plot. Since their
      publication, it was the common view that only the use of the Scatchard plot
      allows solving this problem. However, in some cases, using the Klotz plot is more
      convenient for a representation of experimental data concerning ligand-receptor
      interaction, though usually, this plot was used only for the evaluation of
      receptor affinity with one class of binding sites. In the present paper, it was
      demonstrated that Klotz plot also could be used for the evaluation affinity and
      quantity of two classes of binding sites.

PMID- 12204418
TI  - A simple method for the isolation of genomic DNA from mouse tail free of real
      time PCR inhibitors.
AB  - Although real-time PCR is a rapid, quantitative method for the analysis of gene
      and RNA levels, the presence of inhibitors in samples is an obstacle to its
      successful use. We have found that genomic DNA isolated from mouse tail tips
      using a standard proteinase K digestion method caused marked inhibition of real
      time PCR. Inhibition was specific for mouse tail DNA since genomic DNA isolated
      from other tissue sources using the same methodology was readily amplified. We
      have therefore developed a nonproteinase K DNA isolation method involving the use
      of Chelex 100 resin. This method produces mouse tail DNA that is free of real
      time PCR inhibitors.

PMID- 12204419
TI  - Advances in prenatal screening for Down syndrome: II first trimester testing,
      integrated testing, and future directions.
AB  - BACKGROUND: The acceptability of prenatal screening and diagnosis of Down
      syndrome is dependent, in part, on the gestational age at which the testing is
      offered. First trimester screening could be advantageous if it has sufficient
      efficacy and can be effectively delivered. ISSUES: Two first trimester maternal
      serum screening markers, pregnancy-associated plasma protein-A (PAPP-A) and free
      beta-human chorionic gonadotropin (beta-hCG), are useful for identifying women at
      increased risk for fetal Down syndrome. In addition, measurement of an enlarged
      thickness of the subcutaneous fluid-filled space at the back of the neck of the
      developing fetus (referred to as nuchal translucency or NT) has been demonstrated
      to be an indicator for these high-risk pregnancies. When these three parameters
      are combined, estimates for Down syndrome efficacy exceed those currently
      attainable in the second trimester. Women who are screen-positive in the first
      trimester can elect to receive cytogenetic testing of a chorionic villus biopsy.
      The first trimester tests could also, theoretically, be combined with the second
      trimester maternal serum screening tests (integrated screening) to obtain even
      higher levels of efficacy. There are, however, several practical limitations to
      first trimester and integrated screening. These include scheduling of testing
      within relatively narrow gestational age intervals, availability of appropriately
      trained ultrasonographers for NT measurement, risks associated with chorionic
      villus biopsy, and costs. There is also increasing evidence that an enlarged NT
      measurement is indicative of a high risk for spontaneous abortion and for fetal
      abnormalities that are not detectable by cytogenetic analysis. Women whose
      fetuses show enlarged NT, therefore, need first trimester counseling regarding
      their Down syndrome risks and the possibility of other adverse pregnancy
      outcomes. Follow-up ultrasound and fetal echocardiography in the second trimester
      are also indicated. CONCLUSION: First trimester screening appears to be a highly
      effective method to screen for Down syndrome. Women with screen-positive results
      based on NT measurement appear to be at increased risk for diverse fetal
      abnormalities. The finding of a normal fetal karyotype may not, therefore, carry
      a high level of reassurance for a normal baby.

PMID- 12204420
TI  - The harmonization of cardiac troponin I measurement is independent of sample time
      collection but is dependent on the source of calibrator.
AB  - We compared the agreement of cardiac troponin I (cTnI) values between seven cTnI
      assay systems in clinical samples collected from 1 h up to 11 days post acute
      coronary syndrome (ACS), before and after correction for calibration differences
      between systems. Values were referenced to two sources of common calibrator,
      namely, a manufactured cardiac troponin material containing the ternary ICT
      complex, and a serum from an ACS-positive subject. In 38 samples, cTnI varied up
      to sevenfold between systems, the among-systems coefficient of variation ranging
      from 49% to 127%. After correction for method calibration differences by
      reference to the cTnICT material, the inter-method variation was 43% to 99%
      compared with 13% to 68% for the serum-based material. Differences in cTnI
      isoform composition between the materials, or matrix interactions for the cTnICT
      calibrator, might contribute to the variation in harmonization effect. Despite
      the improved comparability of test values by the use of the serum-based
      calibrator, there was a residual variation in test values between systems that
      was not attributable to the time of collection of the sample post ACS. We
      concluded that due to the heterogeneity of clinical samples, use of a pooled
      human serum material might better serve as a secondary reference reagent for cTnI
      measurement.

PMID- 12204421
TI  - Divergence in plasmatic and urinary isoprostane levels in type 2 diabetes.
AB  - BACKGROUND: Oxidative stress is currently suggested as a mechanism underlying
      diabetes. The present study was designed to evaluate isoprostane levels in plasma
      and in urine in type 2 diabetic patients, and to compare them to other currently
      used biomarkers of oxidative stress. METHODS: The work was performed in a control
      group (n = 10) and in a type 2 diabetic group (n = 10). Besides the traditional
      biochemical parameters, we evaluated the plasma and urine levels of isoprostanes
      and malondialdehyde (MDA) as markers of oxidative stress. RESULTS: We found
      increased plasma and urine MDA in the diabetic patients and almost significantly
      decreased plasma vitamin E. Urinary isoprostane levels in diabetic patients were
      increased but they presented a strong tendency to a decrease in plasma
      isoprostanes. It is therefore suggested that, in the studied diabetic patients,
      although the production of isoprostanes in the body was increased (as other
      plasma oxidative stress biomarkers were altered) it did not lead to an increase
      in plasma isoprostane levels. It could be hypothesised that this results from an
      increased elimination of this metabolite and therefore an increased excretion in
      urine. CONCLUSION: Our results showed that the measurement of same oxidative
      stress biomarker, isoprostane, in two different biologic fluids, plasma and
      urine, led to divergent results and emphasised the importance to measure a
      biomarker both in the circulation fluid (plasma) and in the elimination fluid
      (urine), to have a general idea of what is occurring in the organism.

PMID- 12204422
TI  - Semicarbazide-sensitive amine oxidase in pre-eclampsia: no relation with markers
      of endothelial cell activation.
AB  - BACKGROUND: Semicarbazide sensitive amine-oxidase (SSAO) is an adhesion molecule
      and thought to play a role in endothelial cell dysfunction (ECD). SSAO has never
      been associated with markers of ECD. Pre-eclampsia (PE) is, like the early stages
      of atherosclerosis, characterised by ECD. SSAO could contribute to ECD in PE.
      METHODS: Plasma samples were obtained in 14 pre-eclamptic patients and 14 matched
      controls. In these SSAO-activity, von Willebrand factor (vWF) levels and ED1
      fibronectin levels were determined. Placental tissue was collected of 12 pre
      eclamptic pregnancies, 8 preterm deliveries and 12 term controls. In these
      samples, SSAO activity was assessed. In a subset of these placentas,
      immunohistochemical staining was performed for SSAO, ICAM-1 and VCAM-1. RESULTS:
      Plasma SSAO activity was not significantly different between pre-eclamptic
      subjects and controls. VWF and ED1 fibronectin were both significantly increased
      in the pre-eclamptic subjects. There was no correlation between SSAO activity and
      vWF or ED1 fibronectin levels. Placental SSAO activity was not different between
      pre-eclamptic pregnancies, preterm deliveries and term controls. There was strong
      staining of SSAO in vascular smooth muscle cells (VSM) and moderate staining of
      trophoblast in all three groups. Endothelial cell expression of SSAO was only
      seen in term controls and the placentas of pre-eclamptic patients. There was no
      association between the expression of SSAO, ICAM-1 or VCAM-1 in the placentas of
      pre-eclamptic patients. CONCLUSION: SSAO expression and activity are not related
      to markers of ECD.

PMID- 12204423
TI  - HDL3-related decreased serum paraoxonase (PON) activity in uremic patients:
      comparison with the PON1 allele polymorphism.
AB  - BACKGROUND: Patients with chronic renal failure on maintenance haemodialysis (HD)
      are at high risk of atherothrombotic events; an enhanced oxidant stress might
      have a major role. The decrease of human paraoxonase (PON1), an anti-oxidant high
      density lipoprotein (HDL)-linked enzyme, is a possible mechanism for developing
      cardiovascular disease. To ascertain the causes of low PON1 in such patients, we
      investigated the contribution of both PON1 gene polymorphism and individual
      pattern of HDL. METHODS: On 74 HD patients (47 M and 27 F) and on 92 healthy
      individuals (HS, 48 M and 44 F), we studied PON1 activity, PON1 genotype (55 and
      192 PON1 allelic polymorphisms) and the lipid profile, including the HDL
      subfractions. RESULTS: We observed in HD patients the following significant
      differences: (1) decreased median PON1 activity (73.5 vs. 110 U/l); (2) decreased
      mean HDL concentration (1.05 +/- 0.18 vs. 1.55 +/- 0.41 mmol/l); (3) decreased
      mean HDL3 concentration (0.79 +/- 0.21 vs. 1.28 +/- 0.24 mmol/l). Total HDL
      retained about 70% of serum activity, almost completely carried (95%) by the
      HDL3. Finally, PON1 activity remained significantly low in HD vs. HS after
      matching for the allelic polymorphism. CONCLUSIONS: The reduction of the HDL3,
      not the genetic PON1 polymorphism, seems the most important determinant of PON1
      activity reduction in HD.

PMID- 12204424
TI  - An evaluation of level of oxidative stress and protein glycation in nondiabetic
      undialyzed chronic renal failure patients.
AB  - BACKGROUND: Chronic renal failure (CRF) patients on prolonged dialysis and with
      diabetes have been found to have significant alteration in their antioxidant
      status and protein glycation, but little is known about the same in nondiabetic
      undialyzed CRF patients. This study was performed to evaluate (a) the levels of
      oxidative stress and protein glycation in nondiabetic undialyzed CRF patients and
      (b) the possible influence of oxidative stress on protein glycation. DESIGN AND
      METHODS: A case control study was performed on 23 nondiabetic undialyzed CRF
      patients and 17 control subjects. The concentrations of total plasma ascorbic
      acid, whole blood reduced glutathione (GSH) and plasma lipid peroxides were
      measured to evaluate the antioxidant status and oxidative stress. The protein
      glycation was measured from plasma fructosamine normalized for albumin
      concentrations. A partial correlation analysis was carried out to analyze the
      effect of oxidative stress parameters on protein glycation. RESULTS: A
      compromised nonenzymatic defense against free-radical generation was evidenced by
      decreased concentrations of whole blood GSH and plasma ascorbic acid. The
      concentrations of lipid peroxides, fructosamine and fructosamine/albumin ratio
      were significantly (p<0.05) higher in the CRF group when compared with controls.
      The partial correlation analysis revealed that oxidative stress influences
      protein glycation in CRF patients. CONCLUSIONS: Increased oxidative stress might
      have a role in promoting protein glycation in nondiabetic undialyzed CRF
      patients. The reduction of oxidative stress and protein glycation might open new
      therapeutic approaches in treating CRF patients.

PMID- 12204425
TI  - Activated charcoal is more effective than equilibrium dialysis in removing
      Chinese medicines Chan Su and Dan Shen from serum and activated charcoal also
      prevents further absorption of these agents from G.I. tract in mice: monitoring
      the effect in clinical laboratory by measuring digoxin activity in serum.
AB  - BACKGROUND: Chinese medicines are freely available without prescription and are
      widely used by the general population. Chan Su and Dan Shen are both indicated
      for the treatment of cardiac diseases. Severe toxicity from Chan Su has been
      reported. We studied the possibility of removing Chan Su and Dan Shen from human
      sera using activated charcoal and equilibrium dialysis, and also examined the
      potential benefit of preventing absorption of these agents from the G.I. tract in
      the mouse model. METHODS: For in vitro studies, drug-free serum pools were
      supplemented with Chan Su or Dan Shen and then either treated with activated
      charcoal (10 and 25 mg/ml), or passed through a column packed with activated
      charcoal. Serum pools supplemented with Chan Su or Dan Shen were also subjected
      to equilibrium dialysis against phosphate buffer (pH 7.4) using dialysis membrane
      with molecular cut-off of 25,000 Da. Removal of Chan Su or Dan Shen from the
      serum was monitored by measuring the apparent digoxin concentration using the
      fluorescence polarization immunoassay (FPIA) for digoxin (Abbott Laboratories).
      RESULTS: We observed the fast and effective removal of both Chan Su and Dan Shen
      from the serum by activated charcoal. We also observed significant removal of
      both Chan Su and Dan Shen when the serum pools containing these Chinese medicines
      were passed through columns packed with activated charcoal. Although equilibrium
      dialysis was also effective in removing these Chinese medicines from the serum,
      24 h was required for complete removal of Dan Shen activity, and for Chan Su,
      complete removal was not achieved even after 24 h. In our in vivo model, we
      observed significantly less digoxin activity in the group of mice that received
      activated charcoal compared to the control group. CONCLUSIONS: Activated charcoal
      is effective in preventing absorption of these Chinese medicines from the G.I.
      tract and can also remove these agents from the serum.

PMID- 12204426
TI  - An enzymatic method for the measurement of glycated albumin in biological
      samples.
AB  - BACKGROUND: In order to determine glycated albumin more easily and rapidly, we
      developed a new enzymatic method for glycated albumin in blood samples. METHODS:
      The method involves use of albumin-specific proteinase, ketoamine oxidase and
      serum albumin assay reagent. In the assay, glycated albumin is hydrolyzed to
      glycated amino acids by proteinase digestion, and ketoamine oxidase oxidizes the
      glycated amino acids to produce hydrogen peroxide, which is quantitatively
      measured. Glycated albumin is calculated as the percentage of glycated albumin in
      total albumin. RESULTS: The calibration curve for glycated albumin concentration
      was linear (r(p)=0.999) between 0.0 and 50.0 g/l and that for albumin
      concentration was linear (r(p)=0.999) between 0.0 and 60.0 g/l. The analytical
      recoveries of exogenous glycated albumin added to serum were 100-102.5%. The
      within-run and between-run CVs were 0.45-0.67% and 1.09-1.26%, respectively. This
      method was free from interference by bilirubin, chyle, glucose, globulins and
      labile intermediate. Weak interference by hemoglobin and ascorbic acid was
      observed. Glycated albumin detected by the present method was significantly
      correlated with glycated albumin detected by high-performance liquid
      chromatographic (HPLC) method (serum: r(s)=0.989, plasma: r(p)=0.992).
      CONCLUSIONS: This new enzymatic method is simple, rapid, allows multiple
      determinations and enables quantitative analysis of glycated albumin.

PMID- 12204427
TI  - Instability and variability of urinary telopeptides and free crosslinks.
AB  - BACKGROUND: The use of the urinary bone degradation markers, NTx and free Dpd, in
      the diagnosis and monitoring of pathological bone resorption has been studied
      intensely. Urinary NTx and Dpd are normalized by creatinine to account for
      differences in diuresis. METHODS: We investigated the effects of storage (-20
      degrees C for 119 days) on concentrations of NTx, Dpd and creatinine in the urine
      of 40 subjects. Precipitates (visible upon thawing) were resuspended, but
      specimens were not recentrifuged (in contrast to previous experiments). RESULTS:
      After storage at -20 degrees C, the NTx and creatinine concentrations in urine
      specimens were significantly decreased by about 18% and 22% (p < 0.01 and p <
      0.0001), respectively. Thus, the quotient of NTx/creatinine was slightly
      increased after storage (p < 0.05). Free Dpd and free Dpd/creatinine were both
      significantly increased after storage (p < 0.0001)--by about 20% and 60%,
      respectively. CONCLUSIONS: We suggest that storage at -20 degrees C frees Dpd and
      denatures the epitope used in NTx quantification, and that these changes are
      usually masked by the removal of free Dpd via recentrifugation and by the
      decrease in creatinine in NTx/creatinine. Additionally, we suggest that the
      quotient Dpd/NTx should be evaluated as an alternative to normalizing via
      creatinine excretion.

PMID- 12204428
TI  - Urinary creatinine instability falsely increases the deoxypyridinoline/creatinine
      quotient.
AB  - BACKGROUND: The concentration of urinary deoxypyridinoline crosslinks (Dpd) (as
      in line 17)-normalized with respect to the urinary creatinine concentration is
      used as a biochemical marker of pathological bone resorption. METHODS: The effect
      of various storage conditions on the stability of Dpd/creatinine in urine
      specimens was examined in a sample of 14 individuals without aseptic
      endoprosthetic loosening (control) and 14 patients with aseptic endoprosthetic
      loosening (AEL). RESULTS: In the control group, values of Dpd/creatinine measured
      after 1 day of storage at -20 degrees C were significantly greater (p < 0.005)
      than values measured in fresh urine specimens. In the AEL group, increases in
      urinary Dpd/creatinine values were less pronounced (NS to p < 0.05). Increases in
      Dpd/creatinine were primarily the mathematical consequence of significant
      decreases in urinary creatinine concentration in the control group (p < 0.0001)
      and the AEL group (p < 0.05, after at least 7 days of storage). The decrease in
      urinary creatinine concentration appears to reach a plateau--between 75% and 80%
      of the original value--after approximately 10 days of storage. CONCLUSION: To
      prevent falsely increased Dpd/creatinine quotients, we suggest that urinary
      creatinine should be measured exclusively in fresh urine specimens or
      consistently in specimens stored for at least 14 days at -20 or -80 degrees C.

PMID- 12204429
TI  - Effect of Angelica sinensis on the proliferation of human bone cells.
AB  - BACKGROUND: Angelica sinensis, an herbal medicine known for its effect to purify
      blood quality and improve circulation, frequently appears as the main ingredient
      in prescriptions for bone injuries. Currently, how pharmacologically it
      contributes to the reformation of bone is unclear. METHODS: The effect of the
      aqueous extract of Angelica sinensis on bone cells was investigated in vitro for
      the first time. The human osteoprecursor cells (OPC-1) were incubated in the
      medium with different concentrations of the aqueous extract of Angelica sinensis
      and the cell proliferation was studied. RESULTS: When the concentration of
      Angelica sinensis aqueous extract was <125 microg/ml, the proliferation of OPC-1
      was enhanced. However, the proliferation of OPC-1 was inhibited by Angelica
      sinensis extract with the concentrations >250 microg/ml. Under most treatments,
      the cells presented very pale expression for cyclooxygenase-2 (Cox 2) protein;
      slightly intensified band showed at the highest Angelica sinensis concentration,
      1.0 mg/ml during the course of culture. CONCLUSION: The aqueous extract of
      Angelica sinensis was found to directly stimulate the proliferation, alkaline
      phosphatase (ALP) activity, protein secretion and particularly type I collagen
      synthesis of OPC-1 at dose-dependent manner.

PMID- 12204430
TI  - The proMMP-2 activation rate in patients with chronic viral liver disease.
AB  - BACKGROUND: We previously showed that serum promatrix metalloproteinase-2 (proMMP
      2) concentrations were increased in cirrhotic patients, reflecting the increase
      in liver proMMP-2 concentrations. We examined whether the increased proMMP-2
      concentration reflects the biological matrix metalloproteinase-2 (MMP-2)
      activity. METHODS: We measured serum concentrations of active MMP-2 and proMMP-2,
      and calculated the active MMP-2/proMMP-2 ratio as an index of the proMMP-2
      activation rate in chronic viral liver disease. RESULTS: The serum active MMP-2
      concentrations were not altered in chronic liver disease, although the serum
      proMMP-2 concentration was markedly increased in cirrhotic patients. The active
      MMP-2/proMMP-2 ratio decreased with the grade of liver fibrosis, and was
      negatively correlated with serum levels of tissue inhibitor of metalloproteinases
      (TIMP)-2. CONCLUSION: The proMMP-2 activation rate may be inhibited by the
      increased TIMP-2 in liver cirrhosis (LC), resulting in the accumulation of
      basement membrane collagens.

PMID- 12204431
TI  - Quantity of mutant K-ras gene in pancreatic secretions for diagnosis of
      pancreatic carcinoma with different assays: analysis of 100 patients.
AB  - BACKGROUND: Two types of quantitative assay kits for K-ras mutations, PCR
      preferential homoduplex formation assay (PHFA) and enriched PCR and enzyme-linked
      mini-sequence assay (ELMA), were recently developed. The K-ras mutations were
      analyzed using these assays. MATERIALS AND METHODS: DNA was extracted from the
      pancreatic juice which was obtained by endoscopy from 38 patients with pancreatic
      neoplasms (23 adenocarcinomas and 15 intraductal papillary neoplasms) and from 62
      without it. RESULTS: The results of the two methods were mutually correlative. K
      ras mutation was detected at high levels (mutant ras genes occupied >2% of all K
      ras genes) in 25 of the 38 cases (66%) with pancreatic neoplasm. It was also
      detected at high levels in 9 of the 14 cases (64%) with pancreatic cyst. In
      contrast, the mutant gene was detected at a lower level (<2%) in other cases.
      CONCLUSIONS: Quantitative analysis of the mutant ras gene provided a useful tool
      for diagnosing the pancreatic carcinoma when the percentage of the mutant is
      high, especially when the types of mutation were either GAT or GTT.

PMID- 12204432
TI  - Smoking status-dependent association of the 27-bp repeat polymorphism in intron 4
      of endothelial nitric oxide synthase gene with plasma nitric oxide
      concentrations.
AB  - BACKGROUND: Both positive and negative associations between a rare allele of 27
      bp repeat polymorphism (eNOS4b/a polymorphism) in intron 4 of endothelial nitric
      oxide synthase and plasma nitric oxide (NO) concentrations were previously
      reported. Although these conflicting results were suggested to be partly
      accounted for smoking status of subjects, no further studies have been
      accomplished. METHODS: We analyzed eNOS4b/a polymorphism in a group of 393
      healthy Korean subjects and measured their plasma nitrite and nitrate (NO(x))
      concentrations. NO(x) concentrations were measured by the Griess method and the
      genotypes of eNOS4b/a polymorphism determined by the banding pattern on gel
      electrophoresis. RESULTS: The frequency of eNOS4a allele in this study was 11.6%.
      The plasma NO(x) concentrations (in micromol/l) in subjects with eNOS4a allele
      was found to be significantly higher relative to those in eNOS4b allele (49.68 +/
      18.62 and 55.25 +/- 20.87, respectively, P < 0.05), which was valid only in
      smokers. Multiple regression analysis revealed that the most predictive
      contributing factor for plasma NO(x) concentrations was eNOS4a allele (P < 0.01),
      followed by smoking (P < 0.05), total cholesterol (P < 0.05), and triglycerides
      (P < 0.05). CONCLUSION: Our data indicate that there is substantial effect of
      eNOS4b/a polymorphism on the variance of plasma NO(x) concentrations in Korean
      population and that this effect is dependent on smoking status.

PMID- 12204433
TI  - The changing face of newborn screening: diagnosis of inborn errors of metabolism
      by tandem mass spectrometry.

PMID- 12204434
TI  - Effect of NADH on the redox state of human hemoglobin.
AB  - In this work, we report that NADH can increase the autoxidation rate of
      hemoglobin (HbA) in a pH-dependent fashion. During this process, this cofactor is
      itself oxidized. The presence of superoxide dismutase (SOD) and/or catalase (CAT)
      can inhibit this result. At lower pH rates, the effect of NADH on the hemoglobin
      autoxidation rate is more enhanced; in addition, the rate of NADH oxidation is
      increased. Our data indicates that the reduced pyridine nucleotide may influence
      the redox state of human hemoglobin by a mechanism, which probably involves free
      radical species.

PMID- 12204435
TI  - Simple non-radiochemical HPLC-linked method for screening for purine metabolism
      disorders using dried blood spot.
AB  - BACKGROUND: Pathologies associated with rare inherited disorders affecting purine
      metabolic pathways range from renal failure to neurological dysfunction and
      immunodeficiency. The disorders are usually diagnosed by measuring enzyme
      activities in hemolysates. A non-radiochemical HPLC-linked method is described
      for simultaneous determination of the activities of hypoxanthine-guanine
      phosphoribosyltransferase (HPRT: E.2.4.2.8.), adenine phosphoribosyltransferase
      (APRT: E.2.4.2.7.), adenosine deaminase (ADA: E.3.5.4.4.) and purine nucleoside
      phosphorylase (PNP: E.2.4.2.1.) in dried blood spots. METHOD: 7-mm-diameter blood
      spots stored at 4 degrees C or room temperature were transferred to an Eppendorf
      tube and eluted with 500-microl 0.1 mol/l Tris-HCl buffer, pH 7.4. The eluate was
      added to substrate solutions and incubated at 37 degrees C. Reaction products
      were analysed by HPLC. RESULTS AND CONCLUSIONS: The enzyme activities tested in
      spot eluates were similar to those in erythrocyte lysates from the same subjects.
      None of the enzymatic activities tested were significantly affected by different
      storage temperatures. The main advantages of the proposed method are small blood
      volume required, easy sample collection and transfer, and accurate results. The
      method is therefore suitable for screening inborn errors of purine metabolism
      even in newborns.

PMID- 12204436
TI  - Serum adenosine deaminase activity in women with hyperemesis gravidarum.
AB  - BACKGROUND: Serum adenosine deaminase (ADA) activity increases in diseases where
      cellular immunity is stimulated. Since hyperemesis gravidarum is characterized by
      enhanced cell-mediated immunity, serum ADA activity may be altered. The present
      study evaluated the relation between serum ADA activity and changes in cell
      mediated immunity as causes of changes in ADA activity in hyperemesis gravidarum.
      METHODS: Serum activities of total ADA and its isoenzymes, ADA1 and ADA2, were
      measured in women with hyperemesis gravidarum (n = 24) and normal pregnancies (n
      = 24). Peripheral blood lymphocyte and monocyte counts were also measured.
      RESULTS: In hyperemesis gravidarum, serum total ADA and ADA2 activities averaged
      16.8 +/- 0.5 and 13.3 +/- 0.7 U/l, respectively, which were significantly higher
      than those in normal pregnancies (10.2 +/- 0.5 and 7.8 +/- 0.5 U/l, respectively)
      (p < 0.05). The mean values for ADA1 activity in women with hyperemesis
      gravidarum and normal pregnancies were similar. The increase in total ADA
      activity was accompanied by the increase in lymphocyte and monocyte counts.
      CONCLUSIONS: These results suggest that increased serum total ADA activity
      reflects increases in ADA2 activity, which may be at least in part attributed to
      enhanced cell-mediated immunity in hyperemesis gravidarum.

PMID- 12204437
TI  - Alternans and 2:1 rhythms in an ionic model of heart cells.
AB  - ECG alternans is commonly held to be an indicator of electrical instability of
      the heart, but the development of alternans has not yet been fully understood
      theoretically. We investigate the onset of alternans and 2:1 rhythms for
      stimulation at increasing frequencies in the Beeler-Reuter model, a simple ionic
      model of cardiac tissue. We find hysteresis and bistability at the onset of
      alternans; well-timed stimuli can switch between the two limit cycles. We
      determine quantitatively the effect of blocking specific ionic currents.
      Moreover, we find that calcium buffers generally promote alternans.

PMID- 12204438
TI  - Influence of inorganic pyrophosphate on the kinetics of muscle pyruvate kinase: a
      simple nonallosteric feedback model.
AB  - Potassium pyrophosphate was used instead of ATP as a model ligand for magnesium
      cation for the study of effector influence on the kinetics of pyruvate kinase
      muscle isozyme M(1). The pyruvate kinase activation by low concentration of
      pyrophosphate and inhibition by high concentration of pyrophosphate was
      considered to be the result of reversible reactions of magnesium cation with
      pyrophosphate, ADP, ATP, and PEP. The apparent K(m) and V(m) or in some cases the
      pseudo-first order reaction rate constant (instead of K(m) and V(m)) of pyruvate
      kinase at any given pyrophosphate concentration were analysed as a function of
      concentration of free magnesium cation and its complexes with all ligands present
      in an assay mixture. The functions of reaction parameters with respect to
      concentration of magnesium complexes indicate the coexistence in the reaction
      mixture of simple and mixed complexes of magnesium cation with substrates,
      pyrophosphate, and an enzyme-substrate complex. The parameters of the simulated
      reaction for the proposed interactions fit the measured experimental data. A
      simple model with nonallosteric feedback has been proposed. According to this
      model, mutual and simultaneous interactions of reaction products with substrates
      and with an enzyme result in the coexistence of simple and mixed, labile and
      inert complexes.

PMID- 12204439
TI  - Two-level evolution of foraging agent communities.
AB  - This paper presents simulation results of artificial foraging agent communities.
      The goal of each agent in the community is to find food. Once a food source is
      found, agents eat portions of it and carry some other portions to the nest (in a
      manner similar to ants) until the food is depleted. Agents may also communicate
      food positions when they are near each other. They are given a set of genes that
      control several characteristics, such as their activity, memory, scepticism,
      lying, etc. These genes are recombined and propagated by means of sexual
      reproduction. When one nest is superpopulated with agents, it can break in two
      nests. Agents can communicate only with those belonging to the same nest, which
      gives rise to emergent situations of competition and cooperation between the
      agents in the same nest, as well as competition between different nests. Other
      emergent phenomena such as the propagation of rumours are also studied.

PMID- 12204440
TI  - Reverse engineering of regulatory networks: simulation studies on a genetic
      algorithm approach for ranking hypotheses.
AB  - Reverse engineering algorithms (REAs) aim at using gene expression data to
      reconstruct interactions in regulatory genetic networks. This may help to
      understand the basis of gene regulation, the core task of functional genomics.
      Collecting data for a number of environmental conditions is necessary to
      reengineer even the smallest regulatory networks with reasonable confidence. We
      systematically tested the requirements for the experimental design necessary for
      ranking alternative hypotheses about the structure of a given regulatory network.
      A genetic algorithm (GA) was used to explore the parameter space of a multistage
      discrete genetic network model with fixed connectivity and number of states per
      node. Our results show that it is not necessary to determine all parameters of
      the genetic network in order to rank hypotheses. The ranking process is easier
      the more experimental environmental conditions are used for the data set. During
      the ranking, the number of fixed parameters increases with the number of
      environmental conditions, while some errors in the hypothetical network structure
      may pass undetected, due to a maintained dynamical behaviour.

PMID- 12204441
TI  - Diagrammatic representations for modelling biological knowledge.
AB  - The contemporary research and development context in multidisciplinary biology
      has a serious requirement for integrating knowledge from disparate sources, and
      facilitating much-needed inter- and intra-disciplinary dialogue. A multiplicity
      of models arises when pluralistic approaches to modelling are followed, and also
      when there is not only a requirement to model systems and data, but also
      knowledge of systems and data. The challenges of addressing this multiplicity do
      not only include articulating the structure of complex systems, but also placing
      modelling within the framework of a process as well as a product. The graph
      representations presented here facilitate dialogue, modelling, clarification and
      specification of concepts, and the sharing of terms. This paper explores
      relationships between collections of graph representations. It is hoped that in
      future, when readers look at a node or a process in a graph, they will have a
      much deeper appreciation of relationships and context.

PMID- 12204442
TI  - Mechanical vibration model for chromosomes in metaphase of mitosis and possible
      application to the interruption of cell division.
AB  - The behavior of chromosomes subjected to external mechanical vibration in
      metaphase of mitosis is modeled, and its possible applications to the
      interruption of cell divisions is investigated. The modeling is based on a mass
      and string coupled system where the mass and the string correspond to the
      condensed chromosome and the kinetochore microtubule, respectively. After
      establishing the motion of equation for a chromosome, the frequency response to
      the forced vibration from the outside of the cell is formulated. This will lead
      to an efficient method for kinetic energy transfer to chromosomes by finding the
      resonant frequencies of the cell system. There is a possibility that the
      increased kinetic energy in one chromosome will affect the cell as a whole,
      thereby interrupting the mitosis by the mechanisms that are discussed in this
      report. Rough calculation shows that the vibration in the frequency range of 22
      50 kHz is effective for controlling the mitosis of human cells.

PMID- 12204443
TI  - Changes of the power coefficient in the 'metabolism-mass' relationship in the
      evolutionary process of animals.
AB  - The power coefficient k decreases along evolution in an allometric relationship
      between the oxygen consumption rate and the body mass of animals. This
      theoretical study investigated the role of the power coefficient k and its
      behavior along evolution. The animals were organized in three groups according to
      the values of the power coefficient k as follows: (I) from unicellular
      Prokaryotes to Eukaryotes; (II) from Mytilus and Annelida to Pisces; (III) from
      Reptilia to Mammals and Aves. At the beginning of each animal group (stage), the
      value of k was close to 0.9-1.0 and at the end of the stage it was close to 0.67
      0.70. Exponential sharp increase of the power coefficient k was observed during
      the biological transition from Protozoa to simply organized Metazoa and in the
      transition from Poikylothermic to Homothermic organisms (e.g. from Pisces to
      Reptilia). Also, when using the periodogram regression analysis, a cyclic
      (periodic) pattern in this increase was observed (i.e. period T approximately 8
      11 units, P<0.05). It was postulated that the power coefficient k, as with the
      coefficient a, might represent the increase of complexity of animal organization
      within each group.

PMID- 12204444
TI  - Identification of protein coding genes in genomes with statistical functions
      based on the circular code.
AB  - A new statistical approach using functions based on the circular code classifies
      correctly more than 93% of bases in protein (coding) genes and non-coding genes
      of human sequences. Based on this statistical study, a research software called
      'Analysis of Coding Genes' (ACG) has been developed for identifying protein genes
      in the genomes and for determining their frame. Furthermore, the software ACG
      also allows an evaluation of the length of protein genes, their position in the
      genome, their relative position between themselves, and the prediction of
      internal frames in protein genes.

PMID- 12204446
TI  - Factor analysis of cluster-specific gene expression levels from cDNA microarrays.
AB  - The ever-increasing use of cDNA microarrays in medical research will require the
      development of new algorithms designed specifically for desktop analysis of
      potentially large genetic data sets. This paper describes the CLUSFAVOR algorithm
      (CLUSter and Factor Analysis Using Varimax Orthogonal Rotation) for performing
      cluster and factor analysis of gene expression data obtained from cDNA
      microarrays. A unique feature of the CLUSFAVOR algorithm is that a user can
      perform cluster analysis, view dendograms, and run factor analysis on cluster
      specific genes selected interactively within a single executable program.
      CLUSFAVOR also performs a varimax orthogonal rotation on the extracted factors to
      increase parsimony in the loadings, revealing unique expression profiles for
      genes and expressed sequence tags (ESTs) for which pathway and function
      information is unknown. Microarray data used by the program must be stored and
      input from a disk file. Optional output contains matrices for the input data,
      standardized data, distance matrices, factor loadings, eigenvalues, eigenvectors,
      and percentage of total variation for genes within a cluster. Color cluster image
      displays containing gene expression levels, dendograms for arrays and genes, and
      factor loadings are displayed for the entire group of genes and arrays analyzed
      as well as selected genes within a cluster. Cluster images are also exported to
      JPG and linked to HTML files for viewing.

PMID- 12204447
TI  - A virtual reality-based system for hand function analysis.
AB  - The goal of this study was to demonstrate the usability and usefulness of virtual
      reality technology in assessing hand functions. Ten healthy, non-disabled right
      handed adult volunteers were recruited. Each volunteer used a dataglove to insert
      three-dimensional virtual representations of a cylinder and a prism into the
      target holes. To verify the reliability of the tests, each subject was retested
      twice. The performance testing assessed the visual-motor coordination a person
      needs to achieve a task accurately and within a set time. For each trial, the
      root mean square (RMS) value of the hand movement trajectory was projected onto
      the X, Y, and Z axes. This projection enabled us to measure the extent of the
      genuine, summative displacement of the manipulating hand. The reproducibility of
      the virtual reality assessment was analyzed using the intraclass correlation
      (ICC) approach. The total ICC values of 10 subjects demonstrated a high task
      completion time and RMS on the X and Z axes for the transferring of the prism.
      However, the values were low for the transferring of the cylinder. Because the
      individual coefficients of variations (CVs) varied widely in the moving of both
      the cylinder and the prism, the total (CVs) showed a high reading for the task
      completion time. Although rehabilitation clinics routinely carry out peg-moving
      exercises for disabled patients, our model provides a valuable quantitative real
      time and off-line measure of whole hand functions.

PMID- 12204448
TI  - RIVCAM: a simple video-based kinematic analysis for clinical disorders of gait.
AB  - This paper describes the development of and reports on the accuracy of the
      Rivermead video-based clinical gait analysis method (RIVCAM), a simple and
      comparatively inexpensive movement recording system, which operates at 50 Hz. The
      system comprises five basic steps; firstly subjects are recorded using a PAL
      video camera with white markers affixed to the leg. Second, the video footage is
      digitised onto a computer. Thirdly, a program analyses each frame of footage to
      locate the position of white markers located on the subject's leg. Fourth, the
      data are calibrated (turned into real world co-ordinates) and the markers on the
      legs are identified (such as, heel, toe, etc.). Finally, a kinematic analysis is
      performed on the data, which not only produces a range of relevant spatio
      temporal parameters (such as gait velocity, cadence and stride length), but also
      determines the joint angles at the hip, knee and ankle during the gait cycle.
      Overall the system has a reasonable constant and variable error; in a recorded
      scene measuring 2.6 x 1.6 m and divided into a 3 x 3 grid, a 400 mm bar was
      recorded, on average, as being 401.1 mm with a standard deviation (S.D.) of 2.97
      mm. Although not without shortcomings when compared with more expensive and
      complicated systems, the RIVCAM system represents a valid, reliable and
      affordable way of collecting objective measures of gait in a busy therapy
      setting.

PMID- 12204449
TI  - Design and implementation of a PC-based image-guided surgical system.
AB  - In interactive, image-guided surgery, current physical space position in the
      operating room is displayed on various sets of medical images used for surgical
      navigation. We have developed a PC-based surgical guidance system (ORION) which
      synchronously displays surgical position on up to four image sets and updates
      them in real time. There are three essential components which must be developed
      for this system: (1) accurately tracked instruments; (2) accurate registration
      techniques to map physical space to image space; and (3) methods to display and
      update the image sets on a computer monitor. For each of these components, we
      have developed a set of dynamic link libraries in MS Visual C++ 6.0 supporting
      various hardware tools and software techniques. Surgical instruments are tracked
      in physical space using an active optical tracking system. Several of the
      different registration algorithms were developed with a library of robust math
      kernel functions, and the accuracy of all registration techniques was thoroughly
      investigated. Our display was developed using the Win32 API for windows
      management and tomographic visualization, a frame grabber for live video capture,
      and OpenGL for visualization of surface renderings. We have begun to use this
      current implementation of our system for several surgical procedures, including
      open and minimally invasive liver surgery.

PMID- 12204450
TI  - Software design for analysis of multichannel intracardial and body surface
      electrocardiograms.
AB  - Analysis of multichannel ECG recordings (body surface maps (BSMs) and
      intracardial maps) requires special software. We created a software package and a
      user interface on top of a commercial data analysis package (MATLAB) by a
      combination of high-level and low-level programming. Our software was created to
      satisfy the needs of a diverse group of researchers. It can handle a large
      variety of recording configurations. It allows for interactive usage through a
      fast and robust user interface, and batch processing for the analysis of large
      amounts of data. The package is user-extensible, includes routines for both
      common and experimental data processing tasks, and works on several computer
      platforms. The source code is made intelligible using software for structured
      documentation and is available to the users. The package is currently used by
      more than ten research groups analysing ECG data worldwide.

PMID- 12204451
TI  - Artificial neural networks for infant mortality modelling.
AB  - This work aims to investigate a simple to use and easy to interpret methodology
      for assessing the relative importance of input variables in artificial neural
      networks (ANNs) applied to epidemiological modelling. The independent variables
      were 43 variables of the social, economic, environmental and health sector of 59
      Brazilian municipalities, and the outcomes were infant mortality rates from these
      municipalities. Two assays were developed for the ANN modelling. On the first,
      all 43 variables were taken as input; and on the second, input variables were
      chosen with the help of factor analysis (FA). The relative importance of the
      input variables was investigated by means of bootstrap replications of the ANN
      model on the second assay. Further, multiple linear regression models (LRMs) were
      developed with the same data set and compared to the ANN models. The FA analysis
      allowed the selection of eight variables for the second assay. The percent of
      explained variance R(2) on the ANNs was in the range 0.74-0.80, while linear
      models had R(2)=0.4-0.5. These findings were validated by the bootstrap
      replications, in which the ANN models remained with higher R(2) and lower mean
      square error than the LRMs. The analysis of the best (second) ANN model indicated
      the highest ranking of importance for the variables literacy, agricultural and
      livestock sector jobs, number of commercial establishments and telephones. The
      approach presented here successfully integrated a data-oriented model with expert
      knowledge, indicating the potentiality of ANN modelling in the prediction,
      planning and assessment of public health actions.

PMID- 12204452
TI  - Bivariate linear mixed models using SAS proc MIXED.
AB  - Bivariate linear mixed models are useful when analyzing longitudinal data of two
      associated markers. In this paper, we present a bivariate linear mixed model
      including random effects or first-order auto-regressive process and independent
      measurement error for both markers. Codes and tricks to fit these models using
      SAS Proc MIXED are provided. Limitations of this program are discussed and an
      example in the field of HIV infection is shown. Despite some limitations, SAS
      Proc MIXED is a useful tool that may be easily extendable to multivariate
      response in longitudinal studies.

PMID- 12204454
TI  - Automated external defibrillation as part BLS: implications for education and
      practice.
AB  - The latest Adult Basic Life Support (BLS) guidelines support the inclusion of the
      use of the automated external defibrillator (AED), as part of basic life support
      (BLS). Emphasis on the provision of early defibrillation as part of BLS
      acknowledges the importance of this manoeuvre in the successful termination of
      ventricular fibrillation. The ramifications of such changes for both first
      responders and organisations implementing the guidelines should not be
      underestimated. Issues relating to resourcing, content and duration of training
      and retraining, auditing and evaluation require further exploration. To consider
      these issues now seems particularly pertinent, given the recent launch of the UK
      Government's paper on public health, 'Saving Lives-Our Healthier Nation' which
      seeks to deploy AEDs in busy public places for use by trained members of the lay
      public. Additionally, defibrillation has been identified as one of the key
      competencies that all trained nurses and other health care providers should be
      able to undertake. This paper will consider the background to the current
      guideline changes, analyse the wider implications of translating the
      recommendations into practice, and offer possible solutions to address the issues
      raised. Whilst the analysis is particularly pertinent to the United Kingdom, many
      of the issues raised have international importance.

PMID- 12204455
TI  - Resuscitating an idea: prone CPR.
AB  - Cardiopulmonary resuscitation (CPR) is widely recognized as an essential part of
      the medical response to cardiac arrest. Traditional ('basic') CPR has remained
      essentially unchanged for 40 years despite major problems with training and
      performance, and survival rates from out-of-hospital cardiac arrest remain
      disappointingly low, despite massive resources devoted to CPR training and public
      awareness. More than a decade ago, an article described an alternative method
      prone CPR-which offered many potential advantages over traditional CPR, including
      much simpler training and increased likelihood of actual performance by
      bystanders. The article received little notice at the time; however, the method
      of prone CPR merits further consideration based on a number of subsequent
      supporting studies and case reports. Prone CPR may represent a superior
      alternative to traditional CPR; research into its effectiveness should be given
      high priority.

PMID- 12204456
TI  - Survivors of ventricular tachyarrhythmias due to a transient or reversible
      disorder have a high recurrence rate of lethal cardiac events.
AB  - OBJECTIVES: The recurrence rate of lethal cardiac events after the survival of a
      primary cardiac arrest in patients not having received an implantable
      cardioverter defibrillator (ICD) is investigated. BACKGROUND: According to
      current guidelines, only a small percentage of patients after successful
      cardiopulmonary resuscitation due to an underlying cardiac problem are eligible
      for the implantation of an ICD. METHODS: For retrospective analysis, we used a
      data registry of patients admitted to an emergency department after cardiac
      arrest. Patients who had a primary cardiac cause for their cardiac arrest and who
      did not die within the first month after successful restoration of spontaneous
      circulation were selected. RESULTS: From 1246 patients, 360 met the inclusion
      criteria. A second lethal cardiac event occurred in 94 (26%). Of those 94
      patients, 57 (61%) had good neurological function before their second cardiac
      arrest. Of the survivors with good neurological function, 47 (82%) did not have
      an ICD or a cardiac transplant. Another cardiac arrest due to a primary cardiac
      event occurred in 34 (72%) of these patients. CONCLUSIONS: Cardiac arrest
      survivors without an apparent indication for an ICD have a high risk of suffering
      from a re-arrest of cardiac origin.

PMID- 12204457
TI  - Systolic hypertension and the response to blunt trauma in infants and children.
AB  - OBJECTIVES: To describe age-related systolic blood pressures and pulse rates in
      children following blunt injury. To compare these variables with standard
      reference values for uninjured children at rest and with reference ranges from
      the Advanced Paediatric Life Support (APLS) guidelines. DESIGN: Secondary
      analysis of a prospective cohort. SETTING: Emergency departments throughout
      England and Wales. PARTICIPANTS: 12906 children presenting with acute blunt
      traumatic injury from August 1989 to September 1998. MAIN OUTCOME MEASURES:
      Systolic blood pressure and pulse rate on arrival. RESULTS: Injured children had
      higher systolic blood pressures than the standard quoted 'norms'. Standard
      reference values of systolic blood pressure for children at rest always appeared
      below the 50th percentile for our cohort of injured children (range 7th-27th
      percentiles). Pulse rates for children at rest were always towards the mid-range
      for injured children (range 41st-54th percentiles). These results appeared
      unrelated to injury severity. Age related APLS reference ranges for systolic
      blood pressure and pulse rate resembled the standard reference values for
      uninjured children at rest. CONCLUSIONS: Injured children have a relative
      systolic hypertension compared with children at rest. Pulse rates in the two
      groups are comparable. Following injury, children with apparently 'normal' age
      specific systolic blood pressures on arrival in the Emergency Department are
      relatively hypotensive and should be carefully assessed.

PMID- 12204458
TI  - Normokalemia and hyperglycemia in subarachnoid hemorrhage patients resuscitated
      from prehospital cardiopulmonary arrest.
AB  - Severe metabolic acidosis develops following prolonged periods of cardiopulmonary
      arrest (CPA), and excessive hydrogen ions derived from lactate and other noxious
      acids cause marked hyperkalemia in most CPA patients. This study investigated
      whether the serum electrolyte imbalance in resuscitated CPA patients is affected
      by the etiology of the CPA. Between 1999 and 2000, return of spontaneous
      circulation (ROSC) was achieved and serum electrolyte concentration measurements
      and blood gas analysis (BGA) were performed in 65 of 270 CPA patients treated. Of
      the 65 patients, subarachnoid hemorrhage (SAH) was the cause of the CPA in ten,
      cardiac attack was the cause in 16 and asphyxia was the cause in nine patients.
      The clinical and laboratory data of these 35 patients were retrospectively
      compared among the three groups. The SAH group had significantly lower serum
      potassium concentrations than the other two groups and significantly higher
      glucose concentrations than the asphyxia group. Massive amounts of catecholamines
      are released into the systemic circulation of SAH patients and our results may
      indicate that the amount of catecholamines released in resuscitated SAH patients
      is greater than in heart attack or asphyxia patients, resulting in a lower serum
      potassium concentration despite the presence of severe metabolic acidosis. It
      should be clarified in a prospective study whether the presence of normokalemia
      and hyperglycemia in resuscitated CPA patients reliably predicts the presence of
      SAH.

PMID- 12204459
TI  - Effectiveness of ventilation-compression ratios 1:5 and 2:15 in simulated single
      rescuer paediatric resuscitation.
AB  - Current guidelines for paediatric basic life support (BLS) recommend a
      ventilation-compression ratio of 1:5 during child resuscitation compared with
      2:15 for adults, based on the consensus that ventilation is more important in
      paediatric than in adult BLS. We hypothesized that the ratio 2:15 would provide
      the same minute ventilation as 1:5 during single-rescuer paediatric BLS due to
      the reduced time required to change between ventilations and compressions.
      Fourteen lay rescuers were trained with both ratios and thereafter performed
      single rescuer BLS for approximately 4 min with each of the two ratios in random
      order on a child-sized manikin with a built-in respiratory monitor. Quality of
      chest compressions was assessed by measurement of the rate, depth and position.
      There were no significant differences in tidal volumes or minute ventilation
      between the ratios. Nearly all chest compressions were within acceptable limits
      for depth and place with both methods, but the mean number of chest compressions
      per minute was 48+/-15% greater with ratio 2:15. In conclusion, there was no
      difference in ventilation, but nearly one and a half times as many compressions
      with a ratio of 2:15 than 1:5 for lay rescuers during single rescuer paediatric
      CPR. In order to simplify CPR training for laypersons, we recommend a 2:15 ratio
      for both single- and two-person, adult and paediatric layperson BLS.

PMID- 12204460
TI  - Improving paediatric and newborn life support training by the use of modified
      manikins allowing airway occlusion.
AB  - Manikins currently used in newborn and paediatric resuscitation training are
      limited in their effectiveness by an inability to allow instructors control over
      airway patency. This means that attempts to introduce situations that require
      interventions, other than just appropriate head positioning to achieve successful
      lung inflation, into training or testing scenarios are compromised by the obvious
      visual cue of the manikin's chest movement which may occur even when the head is
      incorrectly positioned. This report describes a modification to manikins, which
      allows such control and discusses its use in improving the effectiveness of
      teaching and the learning experience.

PMID- 12204461
TI  - Effects of hypertonic saline on myocardial blood flow in a porcine model of
      prolonged cardiac arrest.
AB  - OBJECTIVE: To evaluate the effects of hypertonic saline (HS) on myocardial
      reperfusion pressure (MPP) and blood flow (MBF), and cardiac index (CI) during
      and after cardiopulmonary resuscitation (CPR). METHODS: In 21 domestic swine (16
      23 kg) open chest cardiac massage was initiated after 10 min of ventricular
      fibrillation. With the onset of CPR animals randomly received HS (7.2%; 2 ml/kg
      per 10 min or 4 ml/kg per 20 min) or normal saline ((NS); 2 ml/kg per 10 min).
      Haemodynamic variables were monitored continuously, and coloured microspheres
      were used to measure MBF and CI before cardiac arrest (CA), during CPR and 5, 30
      and 120 min after the return of spontaneous circulation. RESULTS: During CPR HS
      significantly increased MPP, MBF, and CI in comparison to NS (P<0.05, resp.,
      MANOVA). Doubling the volume of HS did not improve the haemodynamic effects seen
      after application of 2 ml/kg per 10 min. HS-infusion significantly increased the
      survival rate at 120 min, 6/7 and 5/7 animals receiving 2 ml/kg per 10 min or 4
      ml/kg per 20 min versus 2/7 after NS-infusion (P<0.05, chi(2)-test). CONCLUSIONS:
      HS applied during open chest cardiac massage enhanced MBF and CI, and
      significantly increased resuscitation success and survival rate. The positive
      effects of this promising new approach need to be confirmed in clinical studies.

PMID- 12204462
TI  - Body weight is a predictor of biphasic shock success for low energy transthoracic
      defibrillation.
AB  - BACKGROUND: Transthoracic impedance and current flow are determinants of
      defibrillation success with monophasic shocks. Whether transthoracic impedance,
      either independently or via its association with body weight, is a determinant of
      biphasic waveform shock success has not been determined. METHODS AND RESULTS: We
      studied 22 swine, weighing 18-41 kg. After 15 s of ventricular fibrillation, each
      pig received transthoracic truncated exponential biphasic shocks (5/5 ms), 70-360
      J. Shock success was strongly associated individually with body weight, leading
      edge transthoracic impedance and current at low energy levels (70 and 100 J, all
      P<0.001). Multiple logistic regression analysis showed a significant association
      of body weight with shock success after adjusting for the effect of leading-edge
      impedance (odds ratio of success for 1 kg decrease in weight at 70 J was 1.29,
      95% CI: 1.05-1.59, P=0.02; and at 100 J was 1.30, 95% CI: 1.14-1.49, P<0.0001).
      The same result was observed after adjusting for the effect of leading-edge
      current. At 150 J or higher energy levels, no significant association was
      observed. CONCLUSIONS: Body weight is a determinant of shock success with
      biphasic waveforms at low energy levels in this swine model.

PMID- 12204463
TI  - Myocardial dysfunction after electrical defibrillation.
AB  - We hypothesized that electrical shocks that defibrillate hearts successfully also
      produce myocardial injury, but only in settings in which the myocardium is
      underperfused. Myocardial function was measured in isolated, conventionally
      perfused or underperfused rat hearts during sinus rhythm and conventionally
      perfused or underperfused hearts during ventricular fibrillation (VF) after
      delivery of a sham, a 0.4 J, or a 0.7 J shock. In underperfused hearts, the
      dP/dt, negative dP/dt, left ventricular diastolic pressure and left ventricular
      pressure-volume relationships demonstrated significant impairment in myocardial
      function. Impairment increased with the higher energy shocks. This contrasted
      with normally perfused hearts, whether in sinus rhythm or during VF, in which
      shocks resulted in no significant impairment. Electrical shocks therefore produce
      myocardial injury but only when myocardial perfusion is reduced.

PMID- 12204464
TI  - Vasopressin with delayed combination of nitroglycerin increases survival rate in
      asphyxia rat model.
AB  - Recently, vasopressin has been reported as a more effective drug than epinephrine
      (adrenaline) for cardiopulmonary resuscitation (CPR). However, vasopressin
      decreases myocardial blood flow (MBF) because of its strong vasoconstriction, to
      maintain better coronary perfusion pressure (CPP) compared with epinephrine.
      Nitroglycerin is well known to be able to maintain MBF and increase survival
      rate. In a VF model, vasopressin combined with nitroglycerin maintained CPP;
      however, low survival rates were observed compared with vasopressin alone. We
      investigated the effectiveness of the delayed use of nitroglycerin combined with
      vasopressin in a severe asphyxia model. Fourteen Sprague-Dawley male rats were
      divided into two groups: vasopressin 0.8 U/kg alone (V-Gr.), and nitroglycerin
      0.3 microg/kg 45 s after the administration of 0.8 U/kg vasopressin (VN-Gr.). Six
      min after asphyxia induced by obstructing the tracheal tube, CPR was performed in
      two ways. Three animals resuscitated in the V-Gr. (42%) and six/seven (84%) in
      the VN-Gr. (P<0.05). In the 6 min of asphyxia rat model, vasopressin combined
      with delayed nitroglycerin is more effective than vasopressin alone.

PMID- 12204466
TI  - Clinical resuscitation research and informed consent.

PMID- 12204465
TI  - Mild hypothermia prolongs the survival time during uncontrolled hemorrhagic shock
      in rats.
AB  - OBJECTIVE: To test our hypothesis that during lethal uncontrolled hemorrhagic
      shock (UHS) in rats, mild hypothermia of either 36 or 34 degrees C would prolong
      the survival time in comparison with normotherma of 38 degrees C. METHODS: Twenty
      four rats were lightly anesthetized with halothane and maintained spontaneous
      breathing. UHS was induced by blood withdrawal of 2.5 ml/100 g over 15 min,
      followed by 75% tail amputation. Immediately after the tail cut, the rats were
      randomly divided into three groups (eight rats for each); normothermic Group 1
      (control, rectal temperature 38 degrees C), and mild hypothermic Groups 2 (36
      degrees C) and 3 (34 degrees C). Hypothermia was induced and maintained by body
      surface cooling. The rats were then observed without fluid resuscitation until
      their death (apnea and no pulse) or for a period of 240 min maximum. RESULTS: The
      rectal temperature was cooled down to 36 and 34 degrees C in 5 and 10 min,
      respectively. The mean survival time, which was 76+/-26 min in the control group
      (38 degrees C), was nearly doubled by mild hypothermia, 178+/-65 min for Group 2
      (36 degrees C) (P<0.01 vs. control) and 144+/-54 min for Group 3 (34 degrees C)
      (P<0.05 vs. control) (no significant difference between Group 2 and 3).
      Additional blood losses from tail stumps were not significantly different among
      the three groups. CONCLUSION: Mild hypothermia of either 36 or 34 degrees C
      prolongs the survival time during lethal UHS in rats.

PMID- 12204467
TI  - Nasogastric bag in the diagnosis of tracheoesophageal fistula.

PMID- 12204468
TI  - Proteus syndrome and sudden cardiac arrest; Beware of pulmonary embolism!

PMID- 12204470
TI  - A statement on early defibrillation by the health professions and laymen--21
      December 2001.

PMID- 12204469
TI  - Cardiac arrest and the local emergency cardiac care system.

PMID- 12204471
TI  - Physicochemical properties of quinolone antibiotics in various environments.
AB  - The progress and photosensitivity of quinolone antibiotics are briefly described.
      By the photolysis of nalidixic acid, the loss of -COOH group is observed. The
      photoreaction of fluoroquinolones involves heterolytic C-F bond fragmentation.
      The protonation and divalent cation complexation equilibria are also examined.
      The spectroscopic properties of these drugs are intensively investigated in
      biological mimetic systems such as AOT reverse micelle, and H(2)O-CH(3)OH and
      H(2)O-CH(3)CN mixed solvents. For ofloxacin and norfloxacin, the excited-state
      intramolecular charge transfer (ICT) is observed. So, fluorescence spectra
      exhibit reverse solvatochromism in mixed solvents. The change of radiative and
      non-radiative rate constant can also be explained using this ICT. The influence
      of dielectric effects of solvent is more significant compared with the specific
      hydrogen bonding interaction. Theoretical treatments support all of these
      results.

PMID- 12204472
TI  - Investigations of new lead structures for the design of novel cyclooxygenase-2
      inhibitors.
AB  - On the basis of molecular modelling studies, five new compounds were synthesised
      and studied in an attempt to design new lead structures as selective COX-2
      inhibitors.

PMID- 12204473
TI  - Structure-activity studies with ring E analogues of methyllycaconitine. Synthesis
      and evaluation of enantiopure isomers of selective antagonist at the alpha3
      nicotinic receptor.
AB  - The four diastereomers 4a-d of methyllycaconitine (MLA) analogue 3 ( R
      =(CH(2))(3)Ph, R'=CH(3)) have been synthesized in enantiomerically pure form by
      coupling both (S)- and (R)-2-(methylsuccinimido)benzoic acid (5a and 5b) with
      both (S)- and (R)-3-hydroxymethyl-N-(3-phenyl) propylpiperidine (6a and 6b) using
      TBTU. These compounds were assayed for potency as nicotinic acetylcholine
      receptor (nAChRs) antagonist. All the four diastereomers showed the same potency
      at both the alpha3 and alpha7 receptors as racemic compound 3. This indicates
      that the binding at nicotine acetylcholine receptors (nAchRs) is probably non
      stereospecific.

PMID- 12204474
TI  - Dialkylaminoalkylindolonaphthyridines as potential antitumour agents: synthesis,
      cytotoxicity and DNA binding properties.
AB  - The synthesis of new planar derivatives characterised by the presence of an
      indolonaphthyridine nucleus, carrying a dimethylaminoethyl or a
      dimethylaminopropyl side chain is reported. The antiproliferative activity of the
      new products was tested by means of an in vitro assay on human tumour cell lines
      (HL-60 and HeLa). A number of compounds (1a-d, 1h) showed IC(50) values
      comparable to that obtained with the well-known drug ellipticine on the HL-60
      cell line. The interaction with DNA was also investigated. Linear flow dichroism
      measurements allowed us to understand the interaction geometry. The thermodynamic
      parameters of the binding process, i.e. intrinsic binding constant and exclusion
      parameter, were determined by fluorimetric titration.

PMID- 12204475
TI  - The influence of conformational restriction in the C-terminus of growth hormone
      secretagogues on their potency.
AB  - In order to obtain more potent growth hormone secretagogues, a comparison of
      ipamorelin and NN703 suggested the addition of a polar group at the C-terminus of
      NN703. A study was conducted using constrained amines for this purpose. Here,
      substituted 4-piperidinylamino- and 4-dimethylaminopiperidino-substituents were
      found to give the most active compounds. A replacement of the 4
      dimethylaminopiperidino-substituent with 4-hydroxypiperidino resulted in a series
      of compounds, which showed in vitro activity with EC(50) values in the low
      nanomolar range, and favourable kinetic properties, such as 40% oral
      bioavailability. The most promising compound was also tested in a swine in vivo
      model, resulting in a growth hormone level with a C(max) of over 40 ng mL(-1).

PMID- 12204477
TI  - New bis-aminomercaptotriazoles and bis-triazolothiadiazoles as possible
      anticancer agents.
AB  - A series of bis-phenoxyacetic acids 2 were prepared starting from corresponding
      unsubstituted/substituted 1,4-quinols 1. The fusion of bis-phenoxyacetic acids 2
      with thiocarbohydrazide gave the corresponding bis-[4-amino-5-mercapto-1,2,4
      triazol-3-yl-methyleneoxy]phenylenes (3) in a one pot reaction. The reaction of
      bis-triazoles 3 with various reagents afforded N-bridged heterocycles 4-6 in good
      yields. The newly synthesised compounds were screened for their anticancer
      activity against a panel of 60 cell lines derived from seven cancer types namely,
      lung, colon, melanoma, renal, ovarian, CNS and leukemia. Some of the tested
      compounds showed promising anticancer properties.

PMID- 12204476
TI  - Synthesis and structure-activity relationships of new arylpiperazines: para
      substitution with electron-withdrawing groups decrease binding to 5-HT(1A) and
      D(2A) receptors.
AB  - Compounds in which N-phenylpiperazines were linked by a propyloxy chain to
      position 6 or 7 of a coumarin ring were designed and synthesised, and their
      affinities for 5-HT(1A) and D(2A) receptors were determined by radioligand
      binding assays. The influence of para substitution in the phenyl ring,
      substitution at position 4 of the coumarin system, and the coumarin position at
      which the piperazinylalkyl chain is linked was explored. Electron-withdrawing
      phenyl ring substituents para to the piperazine strongly reduced activity at both
      receptors. Binding at 5HT(1A) was influenced by the bulk of substituents at
      position 4 of the coumarin system, and binding at D(2A) by their electronic
      properties. Neither binding affinity was significantly affected by whether the
      piperazinylalkyl chain was inserted at position 6 or 7 of the coumarin system.

PMID- 12204478
TI  - Vasorelaxing properties of some phenylacridine type potassium channel openers in
      isolated rabbit thoracic arteries.
AB  - In this study, 12 new 2,2,7,7-tetramethyl-9-aryl-2,3,4,5,6,7,9,10-octahydro-1,8
      acridindione derivatives were synthesised and their effects on vascular potassium
      channels and mechanism of induced relaxations on phenylephrine-induced
      contractile responses in isolated rabbit thoracic arteries was investigated.
      Pinacidil was used as standard potassium channel openers in this study. Compounds
      1-12 and pinacidil exerted concentration-dependent relaxation responses
      precontracted phenylephrine in the aortic rings with the efficacy order:
      11>pinacidil>7>2>8>3>1>4>10>6>9>5>12.

PMID- 12204482
TI  - Pain management and beyond: evolving concepts and treatments involving
      cyclooxygenase inhibition.
AB  - Chronic uncontrolled pain may be the greatest health care crisis facing the
      United States. It is the major symptom for which patients seek medical care and
      is associated with substantial economic and psychosocial costs. For many
      patients, particularly the elderly and those suffering from cancer, chronic pain
      is often undertreated. Because pain has an emotional component and is frequently
      accompanied by depression and/or anxiety, patients benefit from a comprehensive
      assessment and multidisciplinary approach to treatment. It is likely that coxibs
      (cyclooxygenase or COX-2-selective inhibitors) will assume an increasingly
      prominent role in the treatment of chronic pain associated with arthritis,
      cancer, and other diseases either as monotherapy or in combination with other
      drugs. In addition, the role of COX-2 inhibition in the prevention and treatment
      of colon cancer, Alzheimer's disease (AD), and other chronic health problems is
      an area currently undergoing intense investigation.

PMID- 12204483
TI  - The demographics of chronic pain management.
AB  - Pain is the most common symptom for which patients seek care. The management of
      pain advanced considerably with the development of cyclooxygenase (COX)-2
      specific inhibitors (coxibs). The clinical usefulness of nonselective
      nonsteroidal anti-inflammatory drugs (NSAIDs) is often limited by the occurrence
      of adverse effects, such as gastric toxicity and bleeding complications, which
      have been attributed to the inhibition of COX-1. At the recommended dosage by
      targeting only COX-2, coxibs offer patients anti-inflammatory and analgesic
      relief with reduced gastrotoxicity compared with traditional NSAIDs.
      Individualization of therapy based on a careful assessment of risks versus
      benefits of different agents is an important consideration in pain management.
      This review summarizes clinical evidence of the comparable efficacy but improved
      tolerability of the coxibs compared with conventional NSAIDs. Important patient
      considerations and risk factors involved in the selection of appropriate
      analgesic/anti-inflammatory treatments are highlighted.

PMID- 12204484
TI  - Role of COX-2 inhibitors in the evolution of acute pain management.
AB  - Management of acute postoperative pain remains suboptimal: nearly 80% of patients
      report moderate to extreme pain following surgery. New pain management paradigms
      incorporate multimodal analgesia, using a combination of analgesics throughout
      the perioperative period to control nociceptive and centrally-stimulated pain.
      Nonselective nonsteroidal anti-inflammatory drugs (NSAIDs) have a role in
      postoperative pain management, but concerns about increased bleeding and
      inhibited wound healing and bone fusion have limited their use. Cyclooxygenase
      (COX)-2-selective inhibitors (coxibs) offer the peripheral pain-relieving
      benefits of nonselective NSAIDs but with fewer adverse GI effects; they also may
      have a role in central sensitization. Clinical trials have demonstrated the
      efficacy and safety of celecoxib and rofecoxib for postoperative pain and for
      preemptive analgesia, and newer agents such as valdecoxib and etoricoxib also
      have demonstrated efficacy in these settings. In addition to their selectivity
      for the COX-2 isozyme overall, unique differences among the coxibs, such as in
      plasma half-life, may impart certain clinical advantages.

PMID- 12204485
TI  - Pharmacoeconomics of coxib therapy.
AB  - The economic evaluation of health care programs is undertaken to assess health
      care costs and benefits. Part of the goal of cost-effectiveness analysis is to
      maximize health benefits given the constraint of limited health care resources.
      The identification of costs is critical in a cost-effectiveness analysis of
      clinical interventions. The recent introduction of the cyclooxygenase (COX)-2
      selective inhibitors, coxibs, for treatment of rheumatoid arthritis,
      osteoarthritis, and acute pain gives rise to cost-effectiveness issues. These new
      agents provide similar efficacy with fewer gastrointestinal events compared with
      nonselective nonsteroidal anti-inflammatory drugs (NSAIDs), but are more
      expensive on a per-dose basis. However, several modeled cost analyses have
      suggested that COX-2 inhibitors are cost effective in subsets of patients because
      they are associated with fewer downstream costs, particularly medical and
      surgical treatment of gastrointestinal adverse effects. Three cost-effectiveness
      models of interventions for rheumatoid arthritis and osteoarthritis, including
      COX-2 inhibitors, are reviewed. Prospective clinical investigation of the
      potential costs and benefits of these new agents is necessary to further support
      these findings.

PMID- 12204486
TI  - The impact of pain management on quality of life.
AB  - Although its inclusion in medical research is relatively recent and its
      interpretation is often variable, quality of life is increasingly being
      recognized as one of the most important parameters to be measured in the
      evaluation of medical therapies, including those for pain management. Pain, when
      it is not effectively treated and relieved, has a detrimental effect on all
      aspects of quality of life. This negative impact has been found to span every age
      and every type and source of pain in which it has been studied. Effective
      analgesic therapy has been shown to improve quality of life by relieving pain.
      Opioid analgesics, cyclooxygenase (COX)-2 inhibitors (or coxibs), and several
      adjuvant analgesics for neuropathic pain have been demonstrated to significantly
      improve quality-of-life scores in patients with pain. Coxibs provide effective,
      well-tolerated analgesia without some of the issues faced with opioids-benefits
      that should translate into improved quality of life. Recent studies have
      demonstrated that the COX-2 inhibitor rofecoxib significantly improves quality of
      life in patients with osteoarthritis and chronic, lower back pain. Quality-of
      life measurements, especially symptom distress scales, can also be used as
      sensitive means of differentiating one agent from another in the same class. In
      future pharmacotherapeutic research, quality of life should be included as an
      outcome domain as are the traditionally measured variables of efficacy and
      safety. In particular, future studies of coxibs should include symptom distress
      scores as important quality-of-life measurements, to identify meaningful
      differences between this new class of analgesics and nonselective nonsteroidal
      anti-inflammatory drugs.

PMID- 12204487
TI  - Preventive Cardiology: How can we do Better? Proceedings of the 33rd Bethesda
      Conference. Bethesda, Maryland, USA. December 18, 2001.

PMID- 12204489
TI  - Task force #1--magnitude of the prevention problem: opportunities and challenges.
      33rd Bethesda Conference.

PMID- 12204490
TI  - Task force #2--the cost of prevention: can we afford it? Can we afford not to do
      it? 33rd Bethesda Conference.

PMID- 12204491
TI  - Task force #3--getting results: who, where, and how? 33rd Bethesda Conference.

PMID- 12204492
TI  - Task force #4--adherence issues and behavior changes: achieving a long-term
      solution. 33rd Bethesda Conference.

PMID- 12204493
TI  - Task force #5--the role of cardiovascular specialists as leaders in prevention:
      from training to champion. 33rd Bethesda Conference.

PMID- 12204494
TI  - Optimizing the diabetic formulary: beyond aspirin and insulin.
AB  - Type 2 diabetes mellitus (DM) afflicts nearly 16 million persons in the U.S.
      Forty million people have impaired glucose tolerance and thus have a 10%
      annualized risk of developing type 2 DM. These prevalence rates are estimated to
      double within the next two decades. At-risk groups appear to be the elderly and
      minorities including African, Hispanic and Native Americans. While the
      epidemiologic underpinnings for this increase are not fully realized, there has
      been a parallel increase in societal obesity, sedentary lifestyle and a marked
      increase in type 2 DM among children. Although there have recently been
      noteworthy advances in the field of cardiovascular medicine, cardiovascular case
      fatalities remain the leading cause of death among diabetic patients. According
      to national health statistics, there continues to be a downward trend in
      cardiovascular mortality and morbidity. This observation has not been
      consistently noted among patients with DM and has led many to re-evaluate current
      treatment goals and pharmacologic regimens for the at-risk patients with type 2
      DM. This shifting treatment paradigm for diabetic patients has led to a
      ratcheting down of targeted risk factor goals including low-density lipoprotein
      cholesterol, systolic and diastolic blood pressure, and serum glucose levels with
      a requisite increase in the number of pharmacologic agents being administered.
      This review focuses on the current adjunctive pharmacologic treatment regimen
      that is well suited for patients with type 2 DM.

PMID- 12204495
TI  - Effect of additional temporary glycoprotein IIb/IIIa receptor inhibition on
      troponin release in elective percutaneous coronary interventions after
      pretreatment with aspirin and clopidogrel (TOPSTAR trial).
AB  - OBJECTIVES: The Troponin in Planned PTCA/Stent Implantation With or Without
      Administration of the Glycoprotein IIb/IIIa Receptor Antagonist Tirofiban
      (TOPSTAR) trial investigated: 1) the amount of troponin T (TnT) release after
      nonacute, elective percutaneous coronary intervention (PCI) in patients
      pretreated with aspirin and clopidogrel; and 2) the effect of additional
      glycoprotein (GP) IIb/IIIa receptor inhibiton on postinterventional TnT release.
      BACKGROUND: No data are available yet as to whether additional administration of
      a GP IIb/IIIa receptor antagonist might be beneficial in patients undergoing
      elective PCI already pretreated with aspirin and clopidogrel. METHODS: After
      bolus application of the study medication (tirofiban [T] or placebo [P]), PCI was
      performed followed by an 18-h continuous infusion of T/P. Primary end point of
      the study was incidence and amount of TnT release after elective PCI after 24 h.
      RESULTS: A total of 12 h after PCI troponin release was detected in 63% of the
      patients receiving P and in 40% of the patients receiving T (p < 0.05), after 24
      h in 69% (P) and 48% (T) (p < 0.05) and after 48 h in 74% (P) versus 58% (T) (p <
      0.08) of the patients. No differences were observed regarding major bleeding,
      intracranial bleeding or nonhemorrhagic strokes. After nine months a reduction of
      combined death/myocardial infarction/target vessel revascularization could be
      observed in the tirofiban group ([T] 2.3% vs. [P] 13.04%, p < 0.05). CONCLUSIONS:
      Troponin T release occurs after successful intervention in 74% of the patients
      undergoing elective PCI after 48 h even after pretreatment with aspirin and
      clopidogrel. The GP IIb/IIIa receptor antagonist tirofiban is able to decrease
      the incidence of troponin release significantly in this patient population.

PMID- 12204496
TI  - Mortality benefit of beta-blockade after successful elective percutaneous
      coronary intervention.
AB  - OBJECTIVES: The goal of this study was to evaluate the mortality benefit of beta
      blockers after successful percutaneous coronary intervention (PCI). BACKGROUND:
      Beta-blockers reduce mortality after myocardial infarction (MI), though limited
      data are available regarding their role after successful PCI. METHODS: Each year
      from 1993 through 1999, the first 1,000 consecutive patients undergoing PCI were
      systematically followed up. Patients presenting with acute or recent MI, shock,
      or unsuccessful revascularization procedures were excluded from the analysis.
      Clinical, procedural, and follow-up data of beta-blocker-treated and non-beta
      blocker-treated patients were compared. A multivariate survival analysis model
      using propensity analysis was used to adjust for heterogeneity between the two
      groups. RESULTS: Of the 4,553 patients, 2,056 (45%) were treated with beta
      blockers at the time of the procedure. Beta-blocker therapy was associated with a
      mortality reduction from 1.3% to 0.8% at 30 days (p = 0.13) and a reduction from
      6.0% to 3.9% at one year (p = 0.0014). This survival benefit of beta-blockers was
      independent of left ventricular function, diabetic status, history of
      hypertension, or history of MI. Using propensity analysis, beta-blocker therapy
      remained an independent predictor for one-year survival after PCI (hazard ratio,
      0.63; 95% confidence interval, 0.46 to 0.87; p = 0.0054). CONCLUSIONS: Within
      this large prospective registry, beta-blocker use was associated with a marked
      long-term survival benefit among patients undergoing successful elective
      percutaneous coronary revascularization.

PMID- 12204497
TI  - Contribution of major cardiovascular risk factors to familial premature coronary
      artery disease: the GENECARD project.
AB  - OBJECTIVES: This study was designed to assess the prevalence of major
      cardiovascular risk factors in familial premature coronary artery disease (P
      CAD), affecting two or more siblings within one sibship. BACKGROUND: Premature
      CAD has a genetic component. It remains to be established whether familial P-CAD
      is due to genes acting independently from major cardiovascular risk factors.
      METHODS: We recruited 213 P-CAD survivors from 103 sibships diagnosed before age
      <or=50 (men) or <or=55 (women) years old. Hypertension, hypercholesterolemia,
      obesity, and smoking were documented at the time of the event in 163 patients
      (145 men and 18 women). Each patient was compared with two individuals of the
      same age and gender, diagnosed with sporadic (nonfamilial) P-CAD, and three
      individuals randomly sampled from the general population. RESULTS: Compared with
      the general population, patients with sporadic P-CAD had a higher prevalence of
      hypertension (29% vs. 14%, p < 0.001), hypercholesterolemia (54% vs. 33%, p <
      0.001), obesity (20% vs. 13%, p < 0.01), and smoking (76% vs. 39%, p < 0.001).
      These risk factors were equally or even more prevalent in patients with familial
      P-CAD (43% [p < 0.05 vs. sporadic P-CAD], 58% [p = 0.07], 21% and 72%,
      respectively). Overall, only 7 (4%) of 163 of patients with familial P-CAD and 22
      (7%) of 326 of patients with sporadic P-CAD had none of these conditions, as
      compared with 167 (34%) of 489 patients in the general population. CONCLUSIONS:
      Classic, remediable risk factors are highly prevalent in patients with familial P
      CAD. Accordingly, a major contribution of genes acting in the absence of these
      risk factors is unlikely.

PMID- 12204498
TI  - Acute type A aortic dissection in the elderly: clinical characteristics,
      management, and outcomes in the current era.
AB  - OBJECTIVES: We sought to evaluate the clinical characteristics, management, and
      outcomes of elderly patients with acute type A aortic dissection. BACKGROUND: Few
      data exist on the clinical manifestations and outcomes of acute type A aortic
      dissection in an elderly patient cohort. METHODS: We categorized 550 patients
      with type A aortic dissection enrolled in the International Registry of Acute
      Aortic Dissection into two age strata (<70 and >or=70 years) and compared their
      clinical features, management, and in-hospital events. RESULTS: Thirty-two
      percent of patients with type A dissection were aged >or=70 years. Marfan
      syndrome was exclusively associated with dissection in the young, whereas
      hypertension, atherosclerosis and iatrogenic dissection predominated in older
      patients. Typical symptoms (abrupt onset of chest or back pain) and signs (aortic
      regurgitation murmur or pulse deficits) of dissection were less common among the
      elderly. Fewer elderly patients were managed surgically than younger patients
      (64% vs. 86%, p < 0.0001). Hypotension occurred more frequently (46% vs. 32%, p =
      0.002) and focal neurologic deficits less frequently (18% vs. 26%, p = 0.04)
      among the elderly. In-hospital mortality was higher among older patients (43% vs.
      28%, p = 0.0006). Logistic regression analysis identified age >or=70 years as an
      independent predictor of hospital death for acute type A aortic dissection (odds
      ratio 1.7, 95% confidence interval 1.1-2.8; p = 0.03). CONCLUSIONS: Our study
      shows significant differences between older (age >or=70 years) and younger (age
      <70 years) patients with acute type A aortic dissection in their clinical
      characteristics, management, and hospital outcomes. Future research should
      evaluate strategies to improve outcomes in this high-risk elderly cohort.

PMID- 12204499
TI  - Effect of long-term therapy with ramipril in high-risk women.
AB  - OBJECTIVES: We evaluated the effects of long-term therapy with the angiotensin
      converting enzyme (ACE) inhibitor ramipril on major cardiovascular (CV) outcomes
      in high-risk women. BACKGROUND: The effect of long-term ACE inhibitor therapy in
      high-risk women without heart failure and with preserved left ventricular (LV)
      systolic function has not been previously reported. METHODS: The Heart Outcomes
      Prevention Evaluation (HOPE) trial is a large, randomized clinical trial that
      evaluated ramipril and vitamin E in high-risk patients. We present the preplanned
      analysis of the effects of ramipril in women in the HOPE study. The study
      randomized 2,480 women aged >or=55 years with vascular disease or diabetes and at
      least one additional CV risk factor and without heart failure or a known low LV
      ejection fraction to ramipril (10 mg/day) or placebo. The primary outcome was the
      composite of myocardial infarction, stroke or CV death. Average follow-up was 4.5
      years. RESULTS: Treatment with ramipril resulted in reduced primary end point
      rates (11.3% vs. 14.9% in the placebo arm; relative risk [RR] 0.77, 95%
      confidence interval [CI] 0.62 to 0.96; p = 0.019), fewer strokes (3.1% vs. 4.8%;
      RR 0.64, 95% CI 0.43 to 0.96; p = 0.029) and fewer CV deaths (4.2% vs. 6.9%; RR
      0.62, 95% CI 0.44 to 0.88; p = 0.0068). There were trends toward reduced rates of
      myocardial infarction, heart failure and all-cause death. The beneficial effect
      of ramipril was similar in women and men. CONCLUSIONS: Treatment with ramipril
      reduces the CV risk in high-risk women without heart failure and with preserved
      LV systolic function.

PMID- 12204500
TI  - Augmentation of myocardial blood flow in hypertensive heart disease by
      angiotensin antagonists: a comparison of lisinopril and losartan.
AB  - OBJECTIVES: The goal of this study was to compare myocardial perfusion reserve
      (MPR) before and after long-term treatment with lisinopril and losartan in
      patients with hypertension and left ventricular hypertrophy (LVH). BACKGROUND:
      Studies have suggested that treatment with angiotensin-converting enzyme
      inhibitors (ACEIs) improves MPR in patients with hypertension by potentiating
      endogenous bradykinins. Because angiotensin receptor blockers (ARBs) lack a
      direct effect on bradykinins, we hypothesized that they may not improve MPR.
      METHODS: We measured pre- and post-treatment myocardial blood flow (MBF) by
      positron emission tomography in 17 patients (lisinopril: 9 patients, losartan: 8
      patients) with hypertension and LVH at baseline and after coronary vasodilation
      with intravenous dipyridamole. In addition, we measured rest and hyperemic blood
      flow in eight normotensive controls. RESULTS: Post-treatment maximal coronary
      blood flow and MPR in the lisinopril group increased significantly compared with
      pretreatment values (3.5 +/- 1.2 vs. 2.6 +/- 1.1 ml/min/g, p = 0.02; 3.7 +/- 1.1
      vs. 2.4 +/- 1 ml/min/g, respectively, p = 0.002, respectively). Post-treatment
      hyperemic flow in the patients treated with lisinopril was not significantly
      different from corresponding measurements in controls (3.5 +/- 1.2 vs. 3.9 +/- 1
      ml/min/g, respectively, p = NS). In the patients treated with losartan, there was
      no difference between pre- and post-treatment MBF values and MPR. CONCLUSIONS:
      Myocardial perfusion reserve and maximal coronary flow improved in asymptomatic
      patients with hypertension-induced LVH after long-term treatment with lisinopril
      but not with losartan. Thus, ACEIs, but not ARBs, might be effective in repairing
      the coronary microangiopathy associated with hypertension-induced LVH.

PMID- 12204501
TI  - Evaluation of the extent and duration of the "ABPM effect" in hypertensive
      patients.
AB  - OBJECTIVES: The goal of this study was to test and quantify the extent and
      duration over time of a possible pressor effect due to ambulatory monitoring.
      BACKGROUND: The use of ambulatory blood pressure monitoring has provided a method
      of blood pressure (BP) assessment that compensates for some of the limitations of
      office values. While a "white-coat" pressor effect on conventional measurements
      has been defined and frequently used for the improved evaluation of hypertensive
      patients, there has not been clear indication that the ambulatory technique could
      also influence BP. METHODS: We studied 538 mild-to-moderate hypertensive patients
      (233 men), 54.2 +/- 14.2 (mean +/- SD) years of age. Blood pressure and heart
      rate were measured at 20-min intervals during the day and at 30-min intervals at
      night for 48 consecutive hours, and physical activity was simultaneously
      evaluated at 1-min intervals with a wrist actigraph. One-third of the patients
      were evaluated twice or more times. RESULTS: In both treated and untreated
      hypertensive patients evaluated for the first time, results indicate a
      statistically significant (p < 0.001) reduction during the second day of
      monitoring as compared with the first in the diurnal mean of systolic and
      diastolic BP, but not in heart rate or physical activity. This pressor effect
      remains statistically significant for the first 6 h to 8 h of monitoring
      independently of gender, days of the week of monitoring or number of
      antihypertensive drugs used by the treated patients. The nocturnal mean of BP
      was, however, similar between both days of sampling. This "ambulatory monitoring
      effect" was not observed when the patients were evaluated after the same sampling
      scheme for the second or successive times three months apart. CONCLUSIONS:
      Ambulatory monitoring for 48 consecutive hours reveals a statistically
      significant pressor response that could reflect a novelty effect in the use of
      the monitoring device for the first time. This effect has marked implications in
      both research and clinical daily practice for a proper diagnosis of hypertension
      and evaluation of treatment efficacy by the use of ambulatory monitoring.

PMID- 12204502
TI  - brain natriuretic peptide levels predict functional capacity in patients with
      chronic heart failure.
AB  - OBJECTIVES: The goal of this study was to determine if brain natriuretic peptide
      (BNP) levels are associated with exercise capacity in patients with chronic heart
      failure (HF). BACKGROUND: Plasma levels of BNP are increased subject to the
      degree of systolic and diastolic left ventricular dysfunction in patients with
      chronic HF. Exercise testing is useful to assess functional capacity and
      prognosis in chronic HF. METHODS: We prospectively studied 70 consecutive
      patients with chronic HF (60.3 +/- 10.4 years, 51 men) referred for
      cardiopulmonary exercise testing. Resting BNP was obtained after 10 min of supine
      rest before symptom-limited bicycle exercise testing. RESULTS: In patients with
      chronic HF, BNP levels correlated with oxygen uptake (VO(2)), both at anaerobic
      threshold (VO(2)AT: r = -0.54, p < 0.001) and peak exercise (peak VO(2): r = 
      0.56, p < 0.001). Impairment of ventilatory efficiency (EqCO(2): r = 0.43, p <
      0.001) and maximum exercise level (W % predicted: r = -0.44, p < 0.05) correlated
      less well with BNP. There was a significant inverse correlation between left
      ventricular ejection fraction and BNP (r = -0.50, p < 0.05). Brain natriuretic
      peptide discriminated well chronic HF patients with a peak VO(2) <10 ml/min/kg
      (area under the receiver operating characteristic [ROC] 0.93) or <14 ml/min/kg
      (area under the ROC 0.72). A BNP >316 pg/ml was associated with a risk ratio of
      6.8 (95% confidence interval, 2.3 to 19.8) for a reduced exercise capacity with a
      peak VO(2) <14 ml/min/kg. CONCLUSIONS: Brain natriuretic peptide is clearly
      associated with exercise capacity in chronic HF. Brain natriuretic peptide levels
      show a significant correlation with the impairment of VO(2) at peak exercise and
      anaerobic threshold. Brain natriuretic peptide is able to differentiate between
      chronic HF patients with moderately and severely impaired exercise capacity.

PMID- 12204503
TI  - Tissue Doppler imaging predicts improved systolic performance and reversed left
      ventricular remodeling during long-term cardiac resynchronization therapy.
AB  - OBJECTIVES: We sought to evaluate the long-term impact of cardiac
      resynchronization therapy (CRT) on left ventricular (LV) performance and
      remodeling using three-dimensional echocardiography and tissue Doppler imaging
      (TDI). BACKGROUND: Three-dimensional echocardiography and TDI allow rapid and
      accurate evaluation of LV volumes and performance. METHODS: Twenty-five
      consecutive patients with severe heart failure and bundle branch block who
      underwent biventricular pacemaker implantation were included. Before and after
      implantation of the pacemaker, three-dimensional echocardiography and TDI were
      performed. These examinations were repeated at outpatient visits every six
      months. RESULTS: Five patients (20%) died during one-year follow-up. In the
      remaining 20 patients, significant reductions in LV end-diastolic volume and LV
      end-systolic volume of 9.6 +/- 14% and 16.5 +/- 15%, respectively (p < 0.01),
      could be demonstrated during long-term follow-up. Accordingly, LV ejection
      fraction increased by 21.7 +/- 18% (p < 0.01). According to a newly developed TDI
      technique-tissue tracking-all regional myocardial segments improved their
      longitudinal systolic shortening (p < 0.01). The extent of the LV base displaying
      delayed longitudinal contraction, as detected by TDI before pacemaker
      implantation, predicted long-term efficacy of CRT. The QRS duration failed to
      predict resynchronization efficacy. CONCLUSIONS: Cardiac resynchronization
      significantly improved LV function and reversed LV remodeling during long-term
      follow-up. Patients likely to benefit from CRT can be identified by TDI before
      implantation of a biventricular pacemaker.

PMID- 12204504
TI  - Upstream stimulation versus downstream stimulation: arrhythmogenesis based on
      repolarization dispersion in the human heart.
AB  - OBJECTIVE: The purpose of this study was to test the hypothesis that a
      ventricular tachycardia (VT) induction site has a shorter action potential
      duration (APD) and effective refractory period (ERP) than a noninducing site,
      resulting in collision against longer ERP ("upstream") as opposed to shorter ERP
      ("downstream," no collision). BACKGROUND: Induction of sustained VT is often
      feasible at one stimulation site while application of an identical pacing
      protocol to another site fails to provoke VT. METHODS: Sixty-nine patients
      undergoing programmed stimulation for VT inducibility had monophasic action
      potential recording/pacing catheters placed in the right ventricular outflow
      tract (RVOT) and right ventricular apex (RVA) simultaneously. Up to three extra
      stimuli were introduced in 5 to 10 ms decrements until ERP was reached. Upon
      completion of a drive cycle at one stimulation site, it was repeated at the
      other. RESULTS: Thirty-eight patients had inducible VT, nine exclusively by RVA
      pacing and nine exclusively by RVOT pacing. Action potential duration and ERP at
      the induction site were significantly shorter (12 +/- 15 ms, p <0.05 and 22 +/-
      14 ms, p < 0.01, respectively, at 600 ms basic cycle length) than at the
      noninduction site. Dispersion of repolarization between corresponding APD at the
      two sites was 58 +/- 41 ms during baseline stimulation (S1) at the inducing site
      but only 37 +/- 23 ms at the noninducing site (p < 0.05). Dispersion increased
      during extra-stimulus application (p < 0.05), reaching a maximum of 75 +/- 45 ms
      during VT induction, but only 53 +/- 33 ms during extra-stimulation at the
      noninduction site. CONCLUSIONS: Site specificity of VT induction underscores the
      role of dispersion of repolarization and refractoriness in facilitating re-entry
      arrhythmias. Upstream stimulation at a site with short repolarization produces
      larger dispersion and facilitates VT induction.

PMID- 12204505
TI  - Cost-effectiveness of targeting patients undergoing cardiac surgery for therapy
      with intravenous amiodarone to prevent atrial fibrillation.
AB  - OBJECTIVES: This study evaluated the cost-effectiveness of administering
      prophylactic intravenous (IV) amiodarone therapy to patients undergoing cardiac
      surgery according to their predicted risk of postoperative atrial fibrillation.
      BACKGROUND: Atrial fibrillation (AF) is a common complication of cardiovascular
      surgery that is associated with a significant increase in hospitalization costs.
      Intravenous amiodarone has been shown to decrease the incidence of postoperative
      AF. METHODS: All 8,709 patients who underwent coronary artery bypass grafting
      (CABG), 1,217 patients who underwent valve replacement and 624 patients who
      underwent CABG and valve replacement procedures (CABG + valve) from January 1,
      1994, to June 30, 1999, at Emory University Hospitals were studied. Models
      predicting the risk of AF were developed using logistic regression; linear
      regression was used to estimate the influence of AF on hospitalization costs.
      Cost-effectiveness was evaluated for patient subsets identified according to
      their predicted risk of AF. RESULTS: Postoperative AF rates were 17.7% for CABG,
      24.6% for valve and 33.8% for CABG + valve. Using 5,000 dollars as an acceptable
      cost per episode of atrial fibrillation averted, prophylactic IV amiodarone in
      CABG patients was not found to be cost-effective. Therapy would be recommended
      for roughly 5% of valve patients with a predicted risk of atrial fibrillation
      >45%, and roughly two thirds of CABG + valve patients who have a predicted risk
      of >30%. CONCLUSIONS: Cost-effectiveness of prophylactic IV amiodarone varies
      according to type of surgery and the predicted risk of atrial fibrillation. Older
      patients undergoing valve replacement, particularly those with a history of
      chronic obstructive pulmonary disease, and those undergoing concomitant CABG are
      likely to be the most appropriate candidates for IV amiodarone therapy in the
      perioperative period.

PMID- 12204506
TI  - Noncontact three-dimensional mapping and ablation of upper loop re-entry
      originating in the right atrium.
AB  - OBJECTIVES: This study was aimed at delineating the reentrant circuit of right
      atrial (RA) upper loop re-entry using noncontact three-dimensional mapping.
      BACKGROUND: Various forms of atypical atrial flutter including lower loop re
      entry and left atrial flutter have been demonstrated. However, little is known
      about upper loop re-entry in the RA. METHODS: The study population consisted of
      eight patients (65 +/- 12 years, seven men) with atypical atrial flutter. Right
      atrial activation during atrial flutter was visualized using a noncontact mapping
      system (EnSite-3000 with Clarity Software, St. Paul, Minnesota) for a three
      dimensional reconstruction of the endocardial depolarization. The narrowest part
      of the re-entrant circuit was targeted using radiofrequency catheter ablation.
      RESULTS: Noncontact mapping showed macro-re-entry confined to the RA free wall
      with RA activation time accounting for 100% of the cycle length (214 +/- 21 ms)
      in all eight patients. Two patients had counterclockwise activation, and six
      patients had clockwise activation around the central obstacle, which was composed
      of the crista terminalis, the area of functional block, and superior vena cava.
      The lower turn-around points were located at the conduction gap in the crista
      terminalis. Radiofrequency linear ablation of the conduction gap in the crista
      terminalis was performed and eliminated atrial flutter in six patients without
      recurrence during a follow-up of 3.2 +/- 1.1 months. CONCLUSIONS: Atypical atrial
      flutter could arise from upper loop re-entry in the RA with conduction through
      the gap in the crista terminalis. Radiofrequency linear ablation of the
      conduction gap was effective in eliminating this atrial arrhythmia.

PMID- 12204507
TI  - Reduced endothelium-dependent and -independent dilation of conductance arteries
      in African Americans.
AB  - OBJECTIVES: The goal of this study was to determine whether racial differences
      exist in the functional behavior of conduit vessels. BACKGROUND: Compared with
      Caucasians, African Americans have a higher prevalence of cardiovascular disease
      and its complications, which may be related to reduced nitric oxide (NO)
      dependent and -independent vasodilation of the microvasculature. However, whether
      a similar impairment is also present at the level of the conductance arteries is
      unknown. METHODS: To this end, we studied endothelium-dependent (posthyperemia
      flow-mediated dilation) and -independent (nitroglycerin) vascular responses of
      the brachial artery by high-resolution ultrasound imaging. There were 46 black
      subjects (23 men and 23 women; age 37 +/- 8 years and 38 +/- 9 years,
      respectively) and 46 white subjects (23 men and 23 women; age 38 +/- 11 years and
      36 +/- 9 years, respectively) in this study. RESULTS: Baseline diameter was
      similar in blacks and in whites (4.4 +/- 0.9 mm and 4.1 +/- 0.7 mm,
      respectively). Mean reactive hyperemia after cuff deflation was similar in the
      two groups (793 +/- 653% in black and 852 +/- 734% in white subjects,
      respectively; p = 0.5). Flow-mediated dilation was significantly lower in black
      compared with white individuals (4.79 +/- 3.5% vs. 8.87 +/- 4.5%, respectively; p
      < 0.0001). Nitroglycerin-mediated dilation was also significantly lower in black
      individuals compared with white individuals (10.99 +/- 4.6% vs. 14.98 +/- 5.4%,
      respectively; p = 0.0002). CONCLUSIONS: African Americans show reduced
      responsiveness of conductance vessels to both endogenous and exogenous NO
      compared with Caucasian Americans. These findings expand our understanding of
      racial differences in vascular function and suggest a mechanistic explanation for
      the increased incidence and severity of cardiovascular disease observed in
      African Americans.

PMID- 12204508
TI  - Acute effects of vasoactive drug treatment on brachial artery reactivity.
AB  - OBJECTIVES: The goal of this study was to investigate whether concomitant therapy
      with vasoactive medications alters the results of noninvasive assessment of
      endothelial function. BACKGROUND: Ultrasound assessment of brachial artery flow
      mediated dilation is emerging as a useful clinical tool. The current practice of
      withholding cardiac medications before ultrasound studies has unknown utility and
      would limit the clinical use of the methodology. METHODS: To determine whether a
      single dose of a vasoactive drug influences brachial reactivity, we examined flow
      mediated dilation and nitroglycerin-mediated dilation in 73 healthy subjects (age
      27 +/- 6 years). Studies were completed at baseline and 3 h after randomized
      treatment with a single oral dose of placebo, felodipine (5 mg), metoprolol (50
      mg), or enalapril (10 mg). To determine if holding vasoactive therapy for 24 h
      before study yields different results than continuation of clinically prescribed
      medications, we examined vascular function in 72 patients (age 57 +/- 10 years)
      with coronary artery disease. Ultrasound studies were performed 24 h after the
      last dose and again 3 h after patients took their clinically prescribed
      medications. RESULTS: In healthy subjects one dose of all three drugs lowered
      blood pressure, and metoprolol also lowered heart rate. However, there was no
      significant effect of treatment on brachial artery dilation. In patients with
      coronary artery disease on chronic treatment, taking prescribed medications
      reduced blood pressure and heart rate, but had no significant effect on brachial
      artery dilation. CONCLUSIONS: Recent administration of commonly used nonnitrate
      vasoactive drugs has no significant effect on brachial reactivity. These findings
      suggest that current practice of withholding cardiac medications before testing
      endothelial function may not be necessary, making this methodology more practical
      for clinical use.

PMID- 12204509
TI  - Coronary endothelial function in hyperhomocysteinemia: improvement after
      treatment with folic acid and cobalamin in patients with coronary artery disease.
AB  - OBJECTIVES: We evaluated the effect of therapy with folic acid and cobalamin on
      coronary endothelial function, expressed as a change in volumetric coronary blood
      flow (CBF), in hyperhomocysteinemic patients with coronary artery disease (CAD).
      BACKGROUND: Hyperhomocysteinemia is an independent risk factor for CAD. The
      mechanism responsible for this increased risk is unclear, but it is generally
      assumed that hyperhomocysteinemia causes endothelial dysfunction. It is unknown
      whether lowering plasma homocysteine levels with folic acid and cobalamin
      improves coronary endothelial function in patients with hyperhomocysteinemia and
      symptomatic CAD. METHODS: Fifteen patients scheduled for elective percutaneous
      transluminal coronary angioplasty (PTCA) with plasma homocysteine levels of
      >or=16 micromol/l were randomized for six months of treatment with folic acid 5
      mg and cobalamin 400 microg daily or placebo. Coronary endothelial function was
      evaluated in a non-PTCA vessel using acetylcholine infusion in dosages of 10(-8)
      M, 10(-7) M, and 10(-6) M. Endothelium- dependent CBF is determined using
      intracoronary Doppler velocity and quantitative coronary angiography at baseline
      and after six months. RESULTS: In the folic acid/cobalamin treated group, CBF
      increased after acetylcholine infusion with 96% (standard deviation 54; 95%
      confidence interval [CI]: 44% to 154%) compared with a decrease of 16% (standard
      deviation 35; 95% CI: -20% to +30%) of the CBF in the placebo-treated group (p <
      0.005). CONCLUSIONS: This is the first prospective randomized placebo-controlled
      intervention study evaluating coronary endothelial function in
      hyperhomocysteinemic patients with CAD. Our results suggest that coronary
      endothelial function improves after treatment with folic acid and cobalamin.

PMID- 12204510
TI  - Large artery stiffness predicts ischemic threshold in patients with coronary
      artery disease.
AB  - OBJECTIVES: The goal of this study was to determine whether large artery
      stiffness contributes to exercise-induced myocardial ischemia in patients with
      coronary artery disease (CAD). BACKGROUND: Large artery stiffness is an
      independent predictor of cardiovascular mortality and a major determinant of
      pulse pressure and, thus, cardiac afterload and coronary perfusion. Clinical
      relevance of the hemodynamic consequences of large artery stiffening has not
      previously been demonstrated in relation to myocardial ischemia. METHODS: We
      hypothesized that stiffer large arteries would reduce myocardial ischemic
      threshold as assessed by time to ST-segment depression of 0.15 mV during a
      treadmill exercise test in patients with CAD. Ninety-six patients with CAD (78
      men) age 62 +/- 9 years (mean +/- SD) were classified as having single (52
      patients), double (31 patients), or triple (13 patients) coronary vessel disease,
      based on angiographically confirmed stenoses >50%. Systemic arterial compliance,
      distensibility index, aortic pulse wave velocity, and carotid augmentation index
      were measured using carotid applanation tonometry and Doppler velocimetry of the
      ascending aorta, at rest. RESULTS: In univariate analysis, all large artery
      stiffness/compliance indexes correlated with time to ischemia (p = 0.01 to
      0.009). Both carotid (p = 0.007) and brachial (p = 0.001) pulse pressure also
      correlated inversely with time to ischemia. In multivariate analysis including
      other major risk factors plus severity of coronary stenosis, indexes of arterial
      stiffness were significant independent predictors of ischemic threshold.
      CONCLUSIONS: Within a patient group with moderate CAD, large artery stiffness was
      a major determinant of myocardial ischemic threshold.

PMID- 12204511
TI  - Long-term intravenous epoprostenol infusion in primary pulmonary hypertension:
      prognostic factors and survival.
AB  - OBJECTIVES: We sought to determine the factors associated with long-term survival
      in patients with primary pulmonary hypertension (PPH) treated with continuous
      epoprostenol infusion. BACKGROUND: Epoprostenol improves survival in patients
      with PPH in New York Heart Association (NYHA) functional class III or IV.
      However, some patients do not benefit from epoprostenol and must be considered
      for lung transplantation. The best timing for listing these patients on a lung
      transplantation program is currently unknown. METHODS: Between December 1992 and
      January 2001, 178 patients with PPH in NYHA functional class III or IV were
      treated with epoprostenol. The 6-min walk test (WT) and right-sided heart
      catheterization were performed at baseline, after three months on epoprostenol
      and thereafter once a year. RESULTS: Overall survival rates at one, two, three,
      and five years were 85%, 70%, 63%, and 55%, respectively. On univariate analysis,
      the baseline variables associated with a poor outcome were a history of right
      sided heart failure, NYHA functional class IV, 6-min WT <or=250 m (median value),
      right atrial pressure >or=12 mm Hg, and mean pulmonary artery pressure <65 mm Hg.
      On multivariate analysis, including both baseline variables and those measured
      after three months on epoprostenol, a history of right-sided heart failure,
      persistence of NYHA functional class III or IV at three months, and the absence
      of a fall in total pulmonary resistance of >30%, relative to baseline, were
      associated with poor survival. CONCLUSIONS: Survival of patients with PPH treated
      with epoprostenol depends on the severity at baseline, as well as the three-month
      response to therapy. These findings suggest that lung transplantation should be
      considered in a subset of patients who remain in NYHA functional class III or IV
      or in those who cannot achieve a significant hemodynamic improvement after three
      months of epoprostenol therapy, or both.

PMID- 12204512
TI  - Severe pulmonary hypertension in patients with severe aortic valve stenosis:
      clinical profile and prognostic implications.
AB  - OBJECTIVES: We analyzed the clinical characteristics and outcomes of 47 patients
      with severe pulmonary hypertension (PHT) and severe aortic valve stenosis (AS)
      from 1987 to 1999. BACKGROUND: The prognostic implications of severe pulmonary
      hypertension in patients with severe AS are poorly understood. METHODS: The mean
      age of patients was 78 years (range 47 to 91 years), and 37 patients (79%) were
      in New York Heart Association (NYHA) functional class III or IV. Aortic valve
      replacement (AVR) was performed in 37 patients (79%) and 10 patients (21%) were
      treated conservatively. RESULTS: In the group that had AVR, there were six
      perioperative deaths (16%) and nine late deaths, resulting in a total mortality
      of 32%. In the conservatively treated group, there were eight deaths (80%) on
      follow-up. Severe PHT was an independent predictor of perioperative mortality.
      However, perioperative mortality was independent of the severity of left
      ventricular systolic dysfunction or concomitant coronary artery bypass grafting.
      Aortic valve replacement was associated with significant improvement in left
      ventricular ejection fraction, the severity of PHT and NYHA functional class. The
      difference between long-term survival of the operative survivors and the expected
      survival from life tables was not statistically significant. CONCLUSIONS: The
      prognosis for patients with AS and severe PHT treated conservatively without AVR
      is dismal. Although AVR is associated with higher than usual mortality, the
      potential benefits outweigh the risk of surgery.

PMID- 12204513
TI  - Endocardial fibroelastosis associated with maternal anti-Ro and anti-La
      antibodies in the absence of atrioventricular block.
AB  - OBJECTIVES: This study was designed to document the association of endocardial
      fibroelastosis (EFE) and maternal autoantibodies. BACKGROUND: Neonatal lupus
      erythematosus is associated with the transplacental passage of maternal anti-Ro
      and anti-La antibodies, leading to complete atrioventricular block (CAVB). In
      some cases, CAVB is associated with EFE. Isolated EFE may be independently
      related to maternal anti-Ro and anti-La antibodies. METHODS: We identified three
      cases (one fetus and two infants, all female) of isolated EFE in infants born to
      autoantibody-positive mothers in the absence of CAVB. Demographics,
      echocardiograms, and pathology were reviewed. Immunohistochemical analyses for
      immunoglobulin (Ig)G, IgM, IgA, T-cell, B-cell, and terminal deoxynucleoleotidyl
      transferase-mediated dUTP-biotin nick end-labeling (TUNEL) (test for cell
      apoptosis) staining were performed on multiple sections of the heart in each case
      and compared with negative controls. RESULTS: Two cases died and one received a
      cardiac transplant. All three cases had histologically confirmed EFE. All cases
      demonstrated significant diffuse IgG infiltration. To a lesser extent, myocardial
      tissue was also positive for IgM, CD43, and Granzyme B. None of the specimens
      were TUNEL positive. CONCLUSIONS: These are the first reported cases of isolated
      EFE associated with maternal anti-Ro and anti-La antibodies in the absence of
      CAVB. The diffuse deposition of IgG and the presence of a T-cell infiltrate
      throughout the myocardium suggest that the transplacental passage of maternal
      autoantibodies induces an immune reaction within the myocardium, leading to
      isolated EFE. Autoantibody-mediated EFE may be an etiologic factor in cases of
      fetal and neonatal "idiopathic" dilated cardiomyopathy.

PMID- 12204514
TI  - Antiapoptotic effect of nicorandil mediated by mitochondrial atp-sensitive
      potassium channels in cultured cardiac myocytes.
AB  - OBJECTIVES: We examined whether nicorandil, a clinically useful drug for the
      treatment of ischemic syndromes, inhibits myocardial apoptosis. BACKGROUND:
      Nicorandil has been reported to have a cardioprotective action through activation
      of mitochondrial ATP-sensitive potassium (mitoK(ATP)) channels. Based on our
      recent observation that mitoK(ATP) channel activation has a remarkable
      antiapoptotic effect in cultured cardiac cells, we hypothesized that the
      protective effects of nicorandil may be at least partially due to an
      antiapoptotic effect. METHODS: Cultured neonatal rat cardiac myocytes were
      exposed to hydrogen peroxide to induce apoptosis. Effects of nicorandil were
      evaluated using a number of apoptotic markers. RESULTS: Exposure to 100 microM
      hydrogen peroxide resulted in apoptotic cell death as shown by TUNEL positivity,
      cytochrome c translocation, caspase-3 activation and dissipation of mitochondrial
      inner membrane potential (Delta(Psi)(m)). Nicorandil (100 microM) suppressed all
      of these markers of apoptosis. Notably, nicorandil prevented Delta(Psi)(m)
      depolarization in a concentration-dependent manner (EC(50) approximately 40
      microM, with saturation by 100 microM), as shown by fluorescence-activated cell
      sorter analysis of cells stained with a fluorescent Delta(Psi)(m)-indicator,
      tetramethylrhodamine ethyl ester (TMRE). Time-lapse confocal microscopy of
      individual cells loaded with TMRE shows that nicorandil suppresses Delta(Psi)(m)
      loss. Subcellular calcein localization revealed inhibition of the mitochondrial
      permeability transition by nicorandil. These protective effects of nicorandil
      were blocked by the mitoK(ATP) channel antagonist 5-hydroxydecanoate.
      CONCLUSIONS: Our findings identify nicorandil as an inhibitor of apoptosis
      induced by oxidative stress in cardiac myocytes, and confirm the critical role of
      mitoK(ATP) channels in inhibiting apoptosis.

PMID- 12204515
TI  - Influence of microbubble surface charge on capillary transit and myocardial
      contrast enhancement.
AB  - OBJECTIVE: The goal of the study was to determine whether microbubble charge
      influences the microvascular retention of microbubble contrast agents.
      BACKGROUND: Interactions between serum proteins and lipid membranes are greater
      with anionic compared with neutral membranes. These interactions may influence
      the microvascular behavior of anionic lipid microbubbles. METHODS: Intravital
      microscopy of the cremaster muscle was performed in six wild-type mice and three
      C3-deficient mice during intravenous injection of lipid-shelled microbubbles with
      either a neutral or a negative charge. Both agents were prepared with and without
      a protective surface layer of polyethyleneglycol (PEG). Complement attachment to
      microbubbles was assessed by flow cytometry with flourescein isothiocyanate
      conjugated anti-C3b monoclonal antibody. Myocardial contrast echocardiography was
      performed in six dogs to assess pulmonary and myocardial retention of
      microbubbles. RESULTS: Size-independent capillary retention of microbubbles,
      occurring for a few seconds to >10 min, was frequently observed with anionic, but
      rarely with neutral, microbubbles (4.3 +/- 0.3 vs. 0.4 +/- 0.1 mm(-3), p < 0.01).
      Anionic microbubble retention was reduced by 70% by surface PEG and was also
      markedly reduced in C3-deficient mice (1.4 +/- 0.1 mm(-3), p < 0.05 vs. wild
      type). Flow cytometry demonstrated complement attachment to only anionic
      microbubbles. Contrast echocardiography indicated both pulmonary and myocardial
      retention of only anionic microbubbles, the latter evidenced by persistent
      opacification >10 min after bolus intravenous injection. CONCLUSIONS: Lipid
      microbubbles with a net negative charge can be retained within capillaries via
      complement-mediated attachment to endothelium. This property may be useful for
      the development of ultrasound contrast agents that can be imaged late after
      venous injection.

PMID- 12204516
TI  - Production of 8-epi prostaglandin F(2alpha) in human platelets during
      administration of organic nitrates.
AB  - OBJECTIVES: The objective of this study was, using isolated platelets as a
      surrogate for vascular cells, to examine the effect of nonintermittent organic
      nitrate administration on 8-epi prostaglandin F(2alpha) (8-epi PGF(2alpha))
      content and the effect of concurrent oral ascorbate administration. BACKGROUND:
      The long-term efficacy of organic nitrates is hampered by hemodynamic tolerance,
      which develops during continuous administration. This has been associated with
      altered production of superoxide and nitric oxide, as well as oxidative stress.
      This effect may be ameliorated by the co-administration of antioxidants. METHODS:
      Ten healthy male subjects received nitroglycerin (NTG) transdermally at a dosage
      of 0.4 mg/h for 3 days with ascorbate or lactose (1.2 g/day). After two weeks
      washout, the treatment was repeated with reversed ascorbate/lactose. Platelets
      were prepared by centrifugation and esterified 8-epi PGF(2alpha) measured at the
      start and finish of each treatment by immunoassay. RESULTS: Nitroglycerin, in the
      absence of supplemental ascorbate, was associated with a significant increase in
      platelet-esterified 8-epi PGF(2alpha), from 32.9 (95% confidence interval [CI]
      11.8 to 54.0) to 51.0 (95% CI 16.3 to 85.7) pg/mg protein (p < 0.05). Co
      administration of ascorbate with NTG resulted in a significant decrease in 8-epi
      PGF(2alpha) production, from 38.8 (95% CI 24.9 to 52.7) to 19.0 (95% CI 13.5 to
      24.5) pg/mg protein (p < 0.05). CONCLUSIONS: Continuous NTG administration
      results in an increase in platelet-esterified 8-epi PGF(2alpha), a free radical
      and cyclooxygenase-dependent compound. This is reversed by co-administration of
      the free radical scavenger ascorbate. Whether this increase is merely a marker
      for increased oxidative stress or a mediator of oxidative injury contributing to
      the hemodynamic changes observed in nonintermittent organic nitrate treatment has
      yet to be resolved.

PMID- 12204517
TI  - Repeated physiologic stresses provide persistent cardioprotection against
      ischemia-reperfusion injury in rats.
AB  - OBJECTIVES: We investigated the time course of myocardial tolerance to ischemia
      reperfusion injury after repeated physiologic or pharmacologic stresses.
      BACKGROUND: Sublethal stress provides cardiac tolerance to ischemia-reperfusion
      injury and increases the activity of manganese superoxide dismutase (Mn-SOD) in
      the myocardium in a biphasic manner. However, few studies have investigated the
      time course of the cardioprotective effects after repeated stresses. METHODS: One
      or two episodes of the same physiologic or pharmacologic stress (exercise, whole
      body hyperthermia, or tumor necrosis factor-alpha treatment), or a combination of
      two different types of stress, were induced after a 48-h interval. The rats were
      then subjected to 20 min of left coronary artery occlusion, followed by 48 h of
      reperfusion. The interval between the last stimulus and the induced ischemia was
      between 0.5 h and 168 h. The incidence of ventricular fibrillation during
      ischemia and the size of the myocardial infarct after reperfusion were then
      examined. RESULTS: When two episodes of physiologic or pharmacologic stress were
      induced, the beneficial effects against ischemia-reperfusion injury were observed
      in a monophasic manner. These effects persisted for a period of 0.5 to 60 h. One
      episode of sublethal stress provoked the same beneficial effects, but in a
      biphasic manner. The increase in Mn-SOD activity in the cardiac tissue resembled
      the time course for cardioprotection against ischemia-reperfusion injury.
      CONCLUSIONS: Two episodes of physiologic or pharmacologic stress can provide
      persistent cardioprotective effects against ischemia-reperfusion injury.

PMID- 12204518
TI  - President's page: ACC chapters: a vital link between cardiologists and their
      college.

PMID- 12204519
TI  - The role of lutein in the prevention of atherosclerosis.

PMID- 12204522
TI  - Controlling the effectiveness of digoxin.

PMID- 12204523
TI  - Long-term outcome in patients with apical hypertrophic cardiomyopathy.

PMID- 12204525
TI  - Interaction of herbal drugs with digoxin.

PMID- 12204526
TI  - A new anti-ErbB2 strategy in the treatment of cancer: prevention of ligand
      dependent ErbB2 receptor heterodimerization.
AB  - Preventing ligand-dependent ErbB2 receptor heterodimers by an anti-ErbB2
      monoclonal antibody shuts down receptor signaling and has potent antitumor
      activity even in tumors that express low levels of ErbB2, a finding that could
      result in a larger number of patients benefiting from anti-ErbB2 therapies.

PMID- 12204527
TI  - Fas function and tumor progression: use it and lose it.
AB  - Recent studies have provided evidence that Fas and FasL interactions are
      important in the control of malignant disease and that changes in the level of
      Fas expression can determine immune escape and therapeutic responses.

PMID- 12204528
TI  - Antiangiogenics meet nanotechnology.
AB  - A mutant Raf-1 gene loaded onto nanoparticles, delivered to tumor vasculature
      with an integrin binding compound, provides effective antiangiogenic gene therapy
      in mice.

PMID- 12204529
TI  - Resistance in the land of molecular cancer therapeutics.
AB  - The fusion tyrosine kinase Bcr-Abl plays a fundamental role in the pathogenesis
      of chronic myeloid leukemia (CML). Imatinib, a potent inhibitor of Bcr-Abl, has
      shown impressive clinical activity in CML patients. However, primary and acquired
      resistance occurs in many patients and is associated with reactivation of Bcr-Abl
      in primary leukemia cells. Studies reported over the past year have begun to
      elucidate the molecular basis of imatinib resistance, which may involve
      amplification of BCR-ABL or, more commonly, mutations that introduce amino acid
      substitutions into the Bcr-Abl kinase. Biochemical analysis and molecular
      modeling indicate that these mutant proteins retain kinase activity but are less
      sensitive to inhibition due to structural changes that perturb drug binding.
      These studies establish a paradigm for elucidating resistance to targeted
      therapeutics.

PMID- 12204530
TI  - The RB and p53 pathways in cancer.
AB  - The life history of cancer cells encompasses a series of genetic missteps in
      which normal cells are progressively transformed into tumor cells that invade
      surrounding tissues and become malignant. Most prominent among the regulators
      disrupted in cancer cells are two tumor suppressors, the retinoblastoma protein
      (RB) and the p53 transcription factor. Here, we discuss interconnecting signaling
      pathways controlled by RB and p53, attempting to explain their potentially
      universal involvement in the etiology of cancer. Pinpointing the various ways by
      which the functions of RB and p53 are subverted in individual tumors should
      provide a rational basis for developing more refined tumor-specific therapies.

PMID- 12204531
TI  - Focus on prostate cancer.

PMID- 12204532
TI  - Multiple BCR-ABL kinase domain mutations confer polyclonal resistance to the
      tyrosine kinase inhibitor imatinib (STI571) in chronic phase and blast crisis
      chronic myeloid leukemia.
AB  - Through sequencing analysis of blood or bone marrow samples from patients with
      chronic myeloid leukemia, we identified BCR-ABL kinase domain mutations in 29 of
      32 patients whose disease relapsed after an initial response to the tyrosine
      kinase inhibitor imatinib. Fifteen different amino acid substitutions affecting
      13 residues in the kinase domain were found. Mutations fell into two groups-those
      that alter amino acids that directly contact imatinib and those postulated to
      prevent BCR-ABL from achieving the inactive conformational state required for
      imatinib binding. Distinct mutations conferred varying degrees of imatinib
      resistance. Mutations detected in a subset of patients with stable chronic phase
      disease correlated with subsequent disease progression. Multiple independent
      mutant clones were detected in a subset of relapsed cases. Our data support a
      clonal selection model of preexisting BCR-ABL mutations that confer imatinib
      resistance.

PMID- 12204533
TI  - Targeting ligand-activated ErbB2 signaling inhibits breast and prostate tumor
      growth.
AB  - ErbB2 is a ligand-less member of the ErbB receptor family that functions as a
      coreceptor with EGFR, ErbB3, and ErbB4. Here, we describe an approach to target
      ErbB2's role as a coreceptor using a monoclonal antibody, 2C4, which sterically
      hinders ErbB2's recruitment into ErbB ligand complexes. Inhibition of ligand
      dependent ErbB2 signaling by 2C4 occurs in both low- and high-ErbB2-expressing
      systems. Since the ErbB3 receptor contains an inactive tyrosine kinase domain,
      2C4 is very effective in blocking heregulin-mediated ErbB3-ErbB2 signaling. We
      demonstrate that the in vitro and in vivo growth of several breast and prostate
      tumor models is inhibited by 2C4 treatment.

PMID- 12204534
TI  - Epigenetic changes in tumor Fas levels determine immune escape and response to
      therapy.
AB  - Epigenetic regulation of gene expression significantly influences cell growth and
      differentiation. Here we show that epigenetic silencing of Fas determines tumor
      growth in vivo and apoptotic sensitivity in vitro. In established tumors with
      epigenetically repressed Fas, restoration of Fas activity either by transfection
      of fas or treatment with Trichostatin A (TSA), an inhibitor of histone
      deacetylase, suppresses tumor growth and restores chemosensitivity. The TSA
      dependent chemosensitivity and tumor growth control require both tumor Fas and
      the host NK (natural killer) cell functions. This work demonstrates the
      importance of epigenetic modification of Fas in tumor progression and immune
      evasion, and emphasizes the essential interplay between Fas and innate immunity
      in the control of chemoresistant tumors.

PMID- 12204535
TI  - Telomere dysfunction provokes regional amplification and deletion in cancer
      genomes.
AB  - Telomere dysfunction and associated fusion-breakage in the mouse encourages
      epithelial carcinogenesis and a more humanized genomic profile that includes
      nonreciprocal translocations (NRTs). Here, array comparative genomic
      hybridization was used to determine the pathogenic significance of NRTs and to
      determine whether telomere dysfunction also drives amplifications and deletions
      of cancer-relevant loci. Compared to tumors arising in mice with intact
      telomeres, tumors with telomere dysfunction possessed higher levels of genomic
      instability and showed numerous amplifications and deletions in regions syntenic
      to human cancer hotspots. These observations suggest that telomere-based crisis
      provides a mechanism of chromosomal instability, including regional
      amplifications and deletions, that drives carcinogenesis. This model provides a
      platform for discovery of genes responsible for the major cancers affecting aged
      humans.

PMID- 12204536
TI  - Mutations in a novel gene lead to kidney tumors, lung wall defects, and benign
      tumors of the hair follicle in patients with the Birt-Hogg-Dube syndrome.
AB  - Birt-Hogg-Dube (BHD) syndrome is a rare inherited genodermatosis characterized by
      hair follicle hamartomas, kidney tumors, and spontaneous pneumothorax.
      Recombination mapping in BHD families delineated the susceptibility locus to 700
      kb on chromosome 17p11.2. Protein-truncating mutations were identified in a novel
      candidate gene in a panel of BHD families, with a 44% frequency of
      insertion/deletion mutations within a hypermutable C(8) tract. Tissue expression
      of the 3.8 kb transcript was widespread, including kidney, lung, and skin. The
      full-length BHD sequence predicted a novel protein, folliculin, that was highly
      conserved across species. Discovery of disease-causing mutations in BHD, a novel
      kidney cancer gene associated with renal oncocytoma or chromophobe renal cancer,
      will contribute to understanding the role of folliculin in pathways common to
      skin, lung, and kidney development.

PMID- 12204537
TI  - Phosphine-induced oxidative damage in rats: role of glutathione.
AB  - Phosphine (PH(3)), generated from aluminium, magnesium and zinc phosphide, is a
      widely used pesticide. PH(3) induces oxidative stress in insects, mammalian
      cells, animals, and humans. The involvement of glutathione (GSH) in PH(3)-induced
      oxidative toxicity is controversial. GSH levels in various tested tissues were
      reduced in aluminium phosphide-poisoned rats and humans, while the levels
      remained unchanged in insects and mammalian cells. This study examines the
      effectiveness of endogenous GSH as a protective agent against PH(3)-induced
      oxidative damage in rats. The association of PH(3)-induced nephrotoxicity and
      cardiotoxicity with free radical production was also tested. Male Wistar rats,
      administered intraperitoneally (I.P.) with PH(3) at 4 mg/kg, were evaluated 30
      min after treatment for PH(3) toxicity to organs. PH(3) significantly decreased
      GSH, GSH peroxidase and catalase, while significantly increased lipid
      peroxidation (as malondialdehyde and 4-hydroxyalkenals), DNA oxidation (as 8
      hydroxydeoxyguaonsoine) and superoxide dismutase (SOD) levels in kidney and
      heart. These changes were significantly alleviated by melatonin (10 mg/kg I.P.,
      30 min before PH(3)), with the exception of SOD activity in heart tissue. The
      study also found that buthionine sulfoximine (1 g/kg I.P., 24 h before PH(3))
      significantly enhanced the effect of PH(3) on GSH loss and lipid peroxidation
      elevation in lung. These findings indicate that (1) endogenous GSH plays a
      crucial role as a protective factor in modulating PH(3)-induced oxidative damage,
      and (2) PH(3) could injure kidney and heart (as noted earlier with brain, liver
      and lung) via oxidative stress and the antioxidant melatonin effectively prevents
      the damage.

PMID- 12204538
TI  - Inhibition of cocaine oxidative metabolism attenuates endotoxin potentiation of
      cocaine mediated hepatotoxicity.
AB  - The oxidative metabolism of cocaine by the microsomal monooxygenase enzymes has
      been postulated to be essential for cocaine mediated hepatotoxicity (CMH).
      Endotoxin (lipopolysaccharide, LPS), a well-known cause of hepatic damage,
      previously has been demonstrated to dramatically increase CMH. The mechanism of
      this interaction has not been clearly elucidated, but cocaine oxidative
      metabolism appears to sensitize hepatocytes so that subsequent exposure to small
      amounts of LPS can further augment CMH. This study was conducted to investigate
      if dimethylaminoethyl-2,2-diphenylvalerate (SKF-525A) pretreatment inhibits LPS
      potentiation of CMH. For 5 consecutive days, male CF-1 mice were administered
      daily SKF-525A (50 mg/kg) or sterile saline followed an hour later by cocaine (20
      mg/kg) or sterile saline. Four hours following the last cocaine or saline
      treatment, the mice were administered sterile saline 12x10(6) EU LPS/kg, i.p. The
      mice were sacrificed 18 h later by decapitation. Pretreatment with SKF-525A
      reversed the hepatic injury caused by cocaine alone or cocaine and LPS
      treatments, as indicated by both histologic evaluation and serum alanine
      transaminase (ALT) and aspartate transaminase (AST) activities. In particular,
      SKF-525A completely reversed the effects of cocaine alone on liver and blood
      reduced gluthathione (GSH), glutathione peroxidase (GPx) and catalase (CAT) and
      hepatic glutathione reductase (GRx) activities. However, SKF-525A was ineffective
      against the effect of LPS alone on liver and blood GPx and CAT or on hepatic GSH
      and GRx, suggesting that these effects were not mediated by cytochrome P450
      oxidative metabolism. The pattern of biochemical changes persisting with SKF-525A
      pretreatment in the LPS and cocaine group resembled those of the LPS alone group.
      The results suggest that cytochrome P450 oxidative metabolism of cocaine is
      largely responsible for CMH with potentiation by LPS achieved through a different
      mechanism involving oxidative stress.

PMID- 12204539
TI  - Effect of chenodeoxycholic acid on the toxicity of 5alpha-cyprinol sulfate in
      rats.
AB  - Attempts are made to elucidate the effect of bile acid chenodeoxycholic acid on
      the toxicity of bile alcohol 5alpha-cyprinol in rats. Twenty-four male Wistar
      rats were divided into four groups and treated orally at 3-days periodic
      treatment with each 160 mg/kg of 5alpha-cyprinol sulfate/chenodeoxycholic acid
      (9:1), 5alpha-cyprinol sulfate and chenodeoxycholic acid for 19 days. After
      treated with 5alpha-cyprinol sulfate/chenodeoxycholic acid (9:1), 5alpha-cyprinol
      sulfate and chenodeoxycholic acid, the relative ratios of liver and kidney weight
      to body weight, the concentrations of red blood cells (RBC), hemoglobin and
      hematocrit in the blood, the levels of aspartate transferase (AST), alanine
      transferase (ALT), alkaline phosphatase (ALP), blood urea nitrogen (BUN) and
      creatinine in the plasma, and the levels of BUN and creatinine in the urine of
      rats were significantly increased, but body weight of rats and the levels of
      Na(+), K(+), Ca(++) in the urine of rats were significantly decreased, especially
      for both groups of 5alpha-cyprinol sulfate/chenodeoxycholic acid (9:1) and 5alpha
      cyprinol sulfate. The pathological examination of liver and kidney also showed
      the cell enlargement and lesion in cell integrity in these treated groups,
      especially for both groups with 5alpha-cyprinol sulfate/chenodeoxycholic acid
      (9:1) and 5alpha-cyprinol sulfate. The toxicity of 5alpha-cyprinol
      sulfate/chenodeoxycholic acid (9:1) and 5alpha-cyprinol sulfate was similar to
      each other, and the toxic effect of chenodeoxycholic acid was less.

PMID- 12204540
TI  - Melatonin attenuates brain mitochondria DNA damage induced by potassium cyanide
      in vivo and in vitro.
AB  - The effect of potassium cyanide on mitochondria DNA (mtDNA) in mouse brain was
      investigated in vivo and in vitro. When potassium cyanide (0, 0.1, 1.0 or 2.0 mM)
      was incubated with a crude mitochondria fraction prepared from mouse brain at 37
      degrees C for 60 min, the damage of mtDNA was observed in a concentration
      dependent manner. However, the mtDNA damage was prevented by a co-treatment with
      melatonin (1.5 mM), a scavenger of hydroxyl radicals (*OH). Furthermore, a
      subcutaneous injection of potassium cyanide (7mg/kg) caused both brain mtDNA
      damage and severe seizures in mouse. The damage of mtDNA and seizures induced by
      potassium cyanide were abolished by the pre-injection of melatonin (20 mg/kg).
      Hydrogen peroxide (1.5 mM) inflicted damage to brain mtDNA in the presence of
      Fe(2+) (3.0 microM). The damage was abolished by the co-treatment with melatonin.
      Furthermore, when cyanide (0, 0.1 or 1.0 mM) was incubated with the crude
      mitochondria fraction prepared from mouse brain, the lipid peroxidation was
      significantly increased in a concentration-dependent manner. The increased lipid
      peroxidation was completely inhibited by the co-treatment with melatonin (1.0
      mM). These results suggest that reactive oxygen species including the *OH may
      play a cardinal role for mtDNA damage induced by potassium cyanide. Hence, the
      present study concluded that melatonin protects against DNA damage induced by the
      *OH produced by cyanide or hydrogen peroxide.

PMID- 12204541
TI  - Molecular inhibitory mechanisms of antioxidant enzymes in rat liver and kidney by
      cadmium.
AB  - Catalase, Mn-superoxide dismutase (MnSOD) and Cu,Zn-superoxide dismutase
      (CuZnSOD) activities were studied in rat liver and kidney 6-48 h after CdCl(2)
      intraperitoneal administration or 10-30 days daily oral CdCl(2) intake in
      drinking water. This approach provided some indications as to the sensitivity of
      each enzyme to cadmium toxicity. These experiments showed that the formation of
      thiobarbituric acid reactive substance (TBARS) did not strictly depend on how
      well the antioxidant enzyme worked. From in vitro experiments it appeared that
      TBARS removal by vitamin E did not restore the three enzyme activities at all. As
      for cadmium's inhibitory mechanism on catalase activity, our data, obtained in
      the pH range 6.0-8.0, are a preliminary indication that the negative effect of
      this metal is probably due to imidazole residue binding of His-74 which is
      essential in the decomposition of hydrogen peroxide. Cadmium inhibition of liver
      mitochondrial MnSOD activity was completely removed by Mn(2+) ions, suggesting
      that the reducing effect on this enzyme is probably due to the substitution of
      cadmium for manganese. We also observed the antioxidant capacity of Mn(2+) ions,
      since they were able to normalize the increased TBARS levels occurring when liver
      mitochondria were exposed to cadmium. The reduced activity of CuZnSOD does not
      seem to be due to the replacement of Zn by Cd, nor to the peroxides formed. As
      this enzyme activity was almost completely recovered after 48 h, we hypothesize
      that the momentary inhibition is imputable to a cadmium/enzyme interaction. This
      causes some perturbation in the enzyme topography which is critical for its
      catalytic activity. The pathological implications linked to antioxidant enzyme
      disorders induced by cadmium toxicity are discussed.

PMID- 12204542
TI  - 2',5'-Dihydroxychalcone down-regulates endothelial connexin43 gap junctions and
      affects MAP kinase activation.
AB  - We examined the effect of 2',5'-dihydroxychalcone on connexin43 (Cx43) expression
      and gap-junctional communication in human umbilical vein endothelial cells
      (HUVEC). The result showed that expression of Cx43 is rapidly reduced by 2',5'
      dihydroxychalcone in a dose-dependent manner, Concomitantly, the communication
      function, determined by fluorescence recovery after photobleaching (FRAP), is
      decreased. We further investigated whether the mitogen-activated protein (MAP)
      kinase and the degradation pathway of gap junctions are involved in these
      processes. Although the change of Cx43 is not affected by the level of fetal calf
      serum (FCS) used in the medium, activation of MAP kinase varies, depending on the
      FCS level. At a low level (0.5%), the chalcone inhibits the activation, like
      PD98059, a specific inhibitor of MAP kinase kinase. However, at a high level
      (20%), MAP kinase is activated. On the other hand, the chalcone's down-regulating
      effect on Cx43, while is totally blocked by protease inhibitors leupeptin and N
      acetyl-leucyl-norleucinal (ALLN), persists in the presence of PD98059, We
      concluded that 2',5'-dihydroxychalcone down-regulates Cx43 expression and gap
      junctional communication in the HUVEC via enhancement of the proteolysis pathway,
      and this compound possesses dual effects on MAP kinase activation.

PMID- 12204543
TI  - Two-year toxicity and carcinogenicity studies in B(6)C(3)F(1) mice with 5-bromo-6
      methoxy-5,6-dihydro-3'-azidothymidine-5'-(p-bromophenyl) methoxyalaninyl
      phosphate (WHI-07), a novel anti-HIV and contraceptive agent.
AB  - The zidovudine derivative, 5-bromo-6-methoxy-5,6-dihydro-3'-azidothymidine-5'-(p
      bromophenyl) methoxy alaninyl phosphate (WHI-07), is a dual-function spermicidal
      and anti-HIV agent with contraceptive and microbicidal activity. In previous two
      subchronic toxicity studies, intravaginal application of 0.5-2.0% WHI-07, for up
      to 13 weeks, was shown to cause no local, systemic or reproductive toxicity. To
      evaluate the toxicity and carcinogenic potential of long-term exposure to WHl-07,
      groups of 50 female B(6)C(3)F(1) mice were given no treatment or exposed
      intravaginally to a gel-microemulsion formulation with and without 2.0% WHI-07, 5
      days per week for 2 years. The dose of WHI-07 was equivalent to 5700 times its
      spermicidal EC(50) and 5.7x10(6) times its anti-HIV IC(50). The endpoints that
      were evaluated included survival, body weight, hematologic and clinical chemistry
      profiles, absolute and relative organ weights, and histopathology. No significant
      differences in mean body weight gain and survival were found among the groups of
      untreated control, placebo control, and 2% WHI-07-treated mice at the end of the
      2-year study. The hematological and clinical chemistry profiles did not reveal
      any toxicologically significant changes that could be attributed to WHI-07
      treatment. No clinically significant changes in absolute and relative organ
      weights were noted in the WHI-07 group. A variety of neoplastic and nonneoplastic
      lesions which were considered incidental, related to aging, or procedural, were
      observed in both the untreated and intravaginally treated groups. The proportion
      of animals with malignant tumors, the total number of malignant tumors, as well
      as the types of malignant tumors in the three groups was similar. The cumulative
      incidence of microscopic lesions in various organs showed that malignant lymphoma
      was the major cause of death in aging female B(6)C(3)F(1) mice, the incidence of
      which was unaffected by intravaginal treatment. We conclude that long-term
      intravaginal administration of WHI-07 is not associated with systemic toxicity or
      increased carcinogenicity in mice. WHI-07 has clinical potential as an active
      ingredient of a safe vaginal/rectal microbicide.

PMID- 12204544
TI  - A narcotic dose of carbon monoxide induces neuronal haeme oxygenase and nitric
      oxide synthetase in sheep.
AB  - Twelve Romney ewes were exposed to either 1% carbon monoxide (CO) in air (n=6) or
      room air alone for 120 min and were killed 15 days later for histological and
      immunohistochemical examination. This dose of CO was narcotic and induced both
      haeme oxygenase and nitric oxide synthetase in brain neurons, but not in
      endothelial cells. The mechanism of the induction is not established here, but
      cellular theories of CO toxicity will need to be re-examined given these results.

PMID- 12204545
TI  - Induction of metallothionein by zinc protects from daunorubicin toxicity in rats.
AB  - Daunorubicin (DNR) is an anthracyline antibiotic used in the treatment of a
      variety of human cancers. Reactive oxygen species (ROS) produced in the
      metabolism of DNR have severe cardiotoxicity which consequently compromises its
      clinical use as anticancer drug. This study aimed to investigate the effect of
      DNR administration on both cardiac and hepatic tissues, and the possible
      protective role of zinc on the cardiotoxicity and hepatotoxicity produced by DNR.
      Administration of 10 or 20 mg/kg DNR to Sprague-Dawley rats, increases serum
      creatine kinase activity, and blood troponin T levels (as cardiotoxicity
      indices), alanine aminotransferase activity (as hepatotoxicity index), as well as
      cardiac and hepatic 2-thiobarbituric acid reactive substances (as an index of
      lipid peroxidation). Treatment with 20 mg/kg Zn prior to DNR, dramatically
      induced metallothionein-1 (MT-1) mRNA and MT protein in both heart and liver
      while DNR alone induced MT, but to a much lower degree than Zn. The analysis of
      MT protein isoforms revealed that MT-1 was the form induced, while
      metallothionein-2 (MT-2) levels remained practically unchanged. The increases in
      both MT protein and MT-1 mRNA ran parallel with the reduction of cardiac and
      hepatic toxicities. Our results indicate that MT induction by Zn is a highly
      effective approach in preventing cardiotoxicity and hepatotoxicity caused by DNR.
      These animal data suggest the use of Zn to reduce DNR-induced cardiotoxicity and
      hepatotoxicity in the chemotherapy of cancer patients.

PMID- 12204546
TI  - Effect of nicotine, cotinine and phenethyl isothiocyanate on 4
      (methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) metabolism in the Syrian
      golden hamster.
AB  - The effect of nicotine, cotinine and phenethyl isothiocyanate (PEITC) on
      metabolism of the tobacco-specific nitrosamine 4-(methylnitrosamino)-1-(3
      pyridyl)-1-butanone (NNK) was studied in the Syrian golden hamster. Urinary
      metabolite profiles were determined in 24 h urine after a single subcutaneous
      (s.c.) administration of [5-(3)H]NNK (80 nmol/kg, s.c.). Co-administration of
      either a 500-fold higher dose of nicotine (40 micromol/kg, s.c.) or a 5000-fold
      higher dose of cotinine (400 micromol/kg, s.c.) significantly (P<0.001) reduced
      metabolic activation of NNK by alpha-hydroxylation to 85 and 71% of control,
      respectively. Co-administration of a 300-fold higher dose of PEITC (1 micromol/g
      diet) slightly reduced alpha-hydroxylation of NNK (94% of control). Metabolism of
      NNK by reduction to 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL) was
      increased by nicotine (155%), and significantly increased by cotinine (670%,
      P<0.001) and PEITC (219%, P<0.01). Detoxification of NNAL by glucuronidation was
      also increased by all three test agents. Detoxification of NNK and NNAL by N
      oxidation was marginally increased by nicotine, reduced by PEITC, and
      significantly reduced by cotinine. The urinary metabolite profiles suggest that
      nicotine, which occurs in concentrations up to 30000-fold higher than NNK in
      mainstream cigarette smoke, and cotinine, its proximal metabolite, may have a
      significant protective effect against in vivo metabolic activation of NNK.

PMID- 12204547
TI  - Depleted uranium-uranyl chloride induces apoptosis in mouse J774 macrophages.
AB  - Depleted uranium entering the body as a result of inhalation or embedded
      fragments becomes associated to a great extent with macrophages. As part of our
      continuing studies on the health effects of internalized depleted uranium, we
      investigated the effect of soluble depleted uranium-uranyl chloride on the mouse
      macrophage cell line, J774. Using a cytochemical staining protocol specific for
      uranium, we found that uranium uptake by the macrophages increased in a time
      dependent manner. Treatment with 1, 10, or 100 microM depleted uranium-uranyl
      chloride resulted in decreased viability of the J774 cells within 24 h. Flow
      cytometric analysis of the treated cells with annexin V showed the translocation
      of phosphatidylserine from the inner face of the plasma membrane to the outer
      surface indicating the loss of phospholipid symmetry and the beginning of the
      apoptotic process. Significant differences in annexin V labeling between control
      cells and cells treated with 100 microM depleted uranium-uranyl chloride were
      apparent within 2 h. Other events associated with apoptosis, including
      morphological changes and DNA fragmentation, were also apparent after depleted
      uranium-uranyl chloride treatment. These results suggest that the uptake and
      concentration of soluble depleted uranium by macrophages initiates events that
      results in the apoptotic death of these cells.

PMID- 12204548
TI  - Correlation between induction of DNA fragmentation in urinary bladder cells from
      rats and humans and tissue-specific carcinogenic activity.
AB  - Seven chemicals, six of which are known to induce epithelial neoplasms of the
      urinary bladder in rats, were assayed for their ability to induce DNA damage in
      primary cultures of rat and human cells from urinary bladder mucosa, and in
      urinary bladder, liver and kidney of intact rats. Significant dose-dependent
      increases of DNA fragmentation, as measured by the Comet assay, were obtained in
      cells from both rats and humans with the following concentrations of five test
      compounds: 2-naphthylamine and N-nitrosodi-n-butylamine 0.5 and 1 mM, phenacetin
      2 and 4 mM, cyclophosphamide from 2 to 8 mM, and o-toluidine 16 and 32 mM.
      Nitrilotriacetic acid (1-4 mM), a rat bladder carcinogen, and 4-aminobiphenyl
      (0.125-0.5 mM), a bladder carcinogen in humans but not in rats, gave a weak
      positive response in rats cells and a more marked response in humans cells. In
      terms of DNA-damaging potency, 4-aminobiphenyl, cyclophosphamide, phenacetin and
      4 nitrilotriacetic acid were more active in human than in rat cells, whereas the
      converse occurred with 2-naphthylamine. Consistently with the results observed in
      vitro statistically significant dose-dependent increases in the average frequency
      of DNA breaks were detected in the urinary bladder mucosa of rats given p.o.
      single doses corresponding to 14 and 12 LD50 of six of the seven test compounds;
      the only one which gave a substantially negative response was 4-aminobiphenyl.
      With the exception of N-nitrosodi-n-butylamine which caused DNA damage in liver
      and of phenacetin and nitrilotriacetic acid which caused damage in kidney in
      agreement with their tumorigenic activity, any substantial evidence of DNA
      lesions in these two organs was absent in rats treated with 12 LD50 of the other
      4 test compounds. These findings give evidence that urinary bladder genotoxic
      carcinogens may be identified by the DNA damage/Comet assay using as targets
      cells of urinary bladder mucosa, and show that the effect may be quantitatively
      different in cells from rats and from human donors.

PMID- 12204549
TI  - Effect of the inhibition of the metabolism of 4-vinylphenol on its hepatotoxicity
      and pneumotoxicity in rats and mice.
AB  - Styrene is known to be both hepatotoxic and pneumotoxic in rodents. 4-Vinylphenol
      (4-VP) has been shown to be a minor metabolite of styrene in some studies and is
      a more potent toxicant in mice than either styrene or styrene oxide. 4-VP is
      metabolized primarily by CYP2E1 and CYP2F2 to an unknown metabolite. The purpose
      of this study was to use inhibitors of these cytochromes P450 to address the
      question of whether the parent compound or a metabolite is responsible for 4-VP
      induced toxicity. Rats as well as mice were found to be susceptible to the
      toxicity of 4-VP. Prior treatment with either diethyldithiocarbamate or 5-phenyl
      1-pentyne as inhibitors of CYP2E1 and CYP2F2 prevented or greatly decreased the
      hepatotoxicity of 4-VP as assessed by measuring serum sorbitol dehydrogenase and
      its pneumotoxicity as determined by measurements of cells, protein and lactate
      dehydrogenase (LDH) activity in bronchoalveolar lavage fluid. Thus the
      hepatotoxicity and pneumotoxicity of 4-VP are due to a metabolite(s) and not the
      parent compound.

PMID- 12204550
TI  - Maternal protein-and-energy restriction reduces the developmental toxicity of
      cyclophosphamide and hydroxyurea in rats.
AB  - In this study, we examined the relationship between maternal weight gain deficits
      induced by protein-and-energy restriction (PER) and pregnancy outcome. We also
      evaluated whether PER would potentiate the developmental toxicity of
      cyclophosphamide (CP) and hydroxyurea (HU). Two independent experiments-
      employing two different methods of inducing protein-and-energy malnourishment
      were performed. In the first experiment, well-nourished (fed ad libitum, normal
      diet, 22% of protein, 11.9 kJ/g) and food restricted (fed approximately half of
      ad libitum food intake, i.e. 12 g/day) rats received CP (0, 5 and 7.5 mg/kg sc)
      on pregnancy day 11. In the second experiment, well-nourished (normal diet, 24%
      of protein, 12.4 kJ/g) and malnourished (protein-and-energy deficient diet, 8% of
      protein, 6.2 kJ/g) rats received HU (0, 300 and 500 mg/kg ip) on pregnancy day
      11. PER alone caused pronounced reductions of pregnancy weight gain and low fetal
      body weight, but induce no embryolethality and, except for a few sternum
      anomalies, no malformation. PER attenuated embryolethal and teratogenic effects
      of CP. PER reduced teratogenicity but did not alter effects of HU on
      embryolethality and fetal body weight. Therefore severe maternal weight gain
      deficits are not necessarily associated to embryolethality and terata and PER
      attenuates the teratogenic effects of CP and HU.

PMID- 12204551
TI  - Leaf extract from Ardisia compressa protects against 1-nitropyrene-induced
      cytotoxicity and its antioxidant defense disruption in cultured rat hepatocytes.
AB  - Herbal tea preparations of Ardisia compressa (AC) have been used in folk medicine
      against liver disorders. The objective of this study was to evaluate the in vitro
      protective effect of an aqueous extract of dry leaves of AC on 1-nitropyrene (1
      NP) induced cytotoxicity on rat hepatocytes. Lipid peroxidation
      (malondialdehyde), antioxidant enzyme activities (glutathione reductase,
      glutathione peroxidase, superoxide dismutase) and glutathione levels were
      studied. After 2 h of incubation, 0.25 microg/ml of 1-NP had an approximately 50%
      cytotoxic effect on hepatocytes. This environmental toxicant also increased
      malondialdehyde (77%), and glutathione peroxidase (46%), producing a significant
      consumption of endogenous antioxidant glutathione. (-)Epigallocatechin 3-gallato
      (EGCG) and AC decreased the viability of hepatocytes after 2 h of incubation at
      concentrations above 3 microg/ml and 2.52 microg, equivalents of (+)catechin/ml,
      respectively. A 100% hepatocyte protection was observed when cells were first
      exposed to AC (2.52 microg, equivalents of (+)catechin/ml), and then followed by
      1-NP (0.25 microg/ml). Cells incubated with AC, either simultaneously or before
      treatment with 1-NP, were protected 75 and 84%, respectively. Cell protection of
      AC was superior to EGCG. Addition of AC to 1-NP (1:10) modulated superoxide
      dismutase and glutathione reductase activities (P<0.005), as well as the cellular
      level of GSH. The results indicate that AC has an antioxidant protective effect
      on rat hepatocytes when exposed to 1-NP.

PMID- 12204552
TI  - Ozone exposure activates oxidative stress responses in murine skin.
AB  - Ozone (O(3)) is among the most reactive environmental oxidant to which skin is
      exposed. O(3) exposure has previously been shown to induce antioxidant depletion
      as well as lipid and protein oxidation in the outermost skin layer, the stratum
      corneum (SC), but little is known regarding the potential effects of O(3) on the
      skin epidermis and dermis. To evaluate such skin responses to O(3), SKH-1
      hairless mice were exposed for 2 h to 8.0 ppm O(3) or to ambient air. O(3)
      exposure caused a significant increase in skin carbonyls (28%) compared to the
      skin of air exposed control animals. An evident increase in 4-hydroxynonenal
      protein adducts was detected after O(3) exposure. O(3) exposure caused a rapid up
      regulation of HSP27 (20-fold), and more delayed induction of HSP70 (2.8-fold) and
      heme oxygenase-1 (5-fold). O(3) exposure also led to the induction of nitric
      oxide synthase (iNOS) 6-12 h following O(3) exposure. We conclude that skin
      exposure to high levels of O(3) not only affects antioxidant levels and oxidation
      markers in the SC, but also induces stress responses in the active layers of the
      skin, most likely by indirect mechanisms, since it is unlikely that O(3) itself
      penetrates the protective SC layers.

PMID- 12204553
TI  - ESR and cell culture studies on free radical-scavenging and antioxidant
      activities of isoflavonoids.
AB  - Isoflavonoids are thought to be the biologically active components in soy that
      play a role in the prevention of coronary heart disease and breast and prostate
      cancer. Mechanisms to explain how isoflavonoids mediate beneficial effects have
      not yet been clearly established. This study was undertaken to investigate the
      free radical-scavenging and antioxidant activities of various structure-related
      isoflavonoids including genistein, daidzein, biochanin A, and genistin in a cell
      free and an endothelial cell model system. Electron spin resonance spectroscopy
      and spin trapping techniques were applied to evaluate the ability of
      isoflavonoids to scavenge hydroxyl, superoxide, nitric oxide,
      diphenylpicrylhydrazyl, galvinoxyl, and lipid-derived radicals. All isoflavonoids
      tested had no significant scavenging effects on the aforementioned radicals in
      concentrations up to 1.0 mM. However, at a physiologically achievable
      concentration of 5 nM, both genistein and daidzein slightly increased
      intracellular-reduced glutathione levels approximately by 10 and 30%,
      respectively, in human endothelial cells, whereas cellular alpha-tocopherol and
      uric acid remained unchanged by the isoflavonoid treatments. Present data
      indicate that free radical-scavenging activities of the isoflavonoids tested
      probably do not substantially contribute to their antioxidant properties. The
      ability of genistein and daidzein to increase cellular GSH (reduced glutathione)
      might be important for their action in biological system.

PMID- 12204554
TI  - Gene transfer in higher animals: theoretical considerations and key concepts.
AB  - Gene transfer technology provides the ability to genetically manipulate the cells
      of higher animals. Gene transfer permits both germline and somatic alterations.
      Such genetic manipulation is the basis for animal transgenesis goals and gene
      therapy attempts. Improvements in gene transfer are required in terms of
      transgene design to permit gene targeting, and in terms of transfection
      approaches to allow improved transgene uptake efficiencies.

PMID- 12204555
TI  - Green fluorescent protein as a reporter of human mu-opioid receptor
      overexpression and localization in the methylotrophic yeast Pichia pastoris.
AB  - The human mu-opioid receptor (HuMOR) was fused in its N-terminus end to the green
      fluorescent protein (GFP) or/and to the c-myc and six histidines tags in its C
      terminus end, and expressed in the methylotrophic yeast Pichia pastoris. Neither
      the C- nor the N-terminal tagging of the receptor does modify its pharmacological
      properties as compared to the untagged receptor. Expression levels of fusion
      receptors determined by GFP fluorescence measurements strongly correlates with
      the number of sites expressed per cell detected through saturation studies (Bmax
      value), thus showing that GFP is an efficient and reliable reporter of the HuMOR
      functional expression. The N- and C-terminus tags have allowed to show that the
      entire molecule is overexpressed. They have permitted in-situ localization
      experiments using fluorescence and electron microscopy techniques and have shown
      a dense intracellular labelling. Above all, the quantification of expression
      levels made possible through fluorescence intensity analysis, have revealed that
      huge amounts of receptor are produced that could not be detected through
      classical binding experiments: for a Bmax value of 1 pmol mg(-1) of receptor
      determined through binding studies, 16 pmol were found in membrane preparations
      using fluorescence and 100 pmol in whole cells. These results should be very
      useful for large-scale production and structural biology of HuMOR, and other G
      protein coupled receptors (GPCRs).

PMID- 12204556
TI  - A novel affinity gene fusion system allowing protein A-based recovery of non
      immunoglobulin gene products.
AB  - An expression vector system has been developed, taking advantage of a novel,
      Staphylococcus aureus protein A (SPA)-binding affinity tag Z(SPA-1), enabling
      straightforward affinity blotting procedures and efficient recovery by affinity
      purification of expressed gene products on readily available reagents and
      chromatography media. The 58 amino acid SPA-binding affinity tag Z(SPA-1), was
      previously selected from a library constructed by combinatorial mutagenesis of a
      protein domain from SPA. An Escherichia coli expression vector for intracellular
      T7 promoter (P(T7)) driven production was constructed with an N-terminal dual
      affinity tag, consisting of a hexahistidyl (His(6)) tag in frame with the Z(SPA
      1) tag, thus allowing alternative affinity recovery methods. To evaluate the
      system, five cDNA clones from a mouse testis cDNA library were expressed, and two
      alternative blotting procedures were developed for convenient screening of
      expression efficiencies. The five produced fusion proteins were recovered on both
      immobilized metal-ion affinity chromatography (IMAC) columns and on Protein A
      based chromatography media, to allow comparative studies. It was found that the
      Protein A-based recovery resulted in the highest degree of purity, and
      furthermore, gene products that were produced as inclusion bodies could after
      denaturation be efficiently affinity purified on Protein A-Sepharose in the
      presence of 0.5 M guanidine hydrochloride. The convenience and robustness of the
      presented expression system should make it highly suitable for various high
      throughput protein expression efforts.

PMID- 12204557
TI  - High-throughput screening for expression of heterologous proteins in the yeast
      Pichia pastoris.
AB  - The methylotrophic yeast Pichia pastoris has become a powerful host for the
      heterologous expression of proteins. In order to provide proteins for the
      'protein structure factory', a structural genomics initiative, we are working on
      the high-throughput expression of human proteins. Therefore, cDNAs are cloned for
      intracellular expression. The resulting fusion proteins carry affinity tags
      (6*HIS and StrepII, respectively) at the N- and C-terminus for the immunological
      detection and chromatographic purification of full-length proteins. Expression is
      controlled by the tightly regulated and highly inducible alcoholoxidase 1 (AOX1)
      promoter. We have developed a cultivation and induction protocol amendable to
      automation to increase the number of clones screened for protein expression. The
      screening procedure is based on a culture volume of 2 ml in a 24-well format.
      Lysis of the cells occurs via a chemical lysis without mechanical disruption.
      Using the optimized feeding and induction protocol, we are now able to screen for
      and identify expression clones which produce heterologous protein with a yield of
      5 mg l(-1) culture volume or higher.

PMID- 12204558
TI  - Enzymatic properties of the low molecular mass endoglucanases Cel12A (EG III) and
      Cel45A (EG V) of Trichoderma reesei.
AB  - Trichoderma reesei produces five known endoglucanases. The most studied are Cel7B
      (EG I) and Cel5A (EG II) which are the most abundant of the endoglucanases. We
      have performed a characterisation of the enzymatic properties of the less well
      studied endoglucanases Cel12A (EG III), Cel45A (EG V) and the catalytic core of
      Cel45A. For comparison, Cel5A and Cel7B were included in the study. Adsorption
      studies on microcrystalline cellulose (Avicel) and phosphoric acid swollen
      cellulose (PASC) showed that Cel5A, Cel7B, Cel45A and Cel45Acore adsorbed to
      these substrates. In contrast, Cel12A adsorbed weakly to both Avicel and PASC.
      The products formed on Avicel, PASC and carboxymethylcellulose (CMC) were
      analysed. Cel7B produced glucose and cellobiose from all substrates. Cel5A and
      Cel12A also produced cellotriose, in addition to glucose and cellobiose, on the
      substrates. Cel45A showed a clearly different product pattern by having
      cellotetraose as the main product, with practically no glucose and cellobiose
      formation. The kinetic constants were determined on cellotriose, cellotetraose
      and cellopentaose for the enzymes. Cel12A did not hydrolyse cellotriose. The
      k(Cat) values for Cel12A on cellotetraose and cellopentaose were significantly
      lower compared with Cel5A and Cel7B. Cel7B was the only endoglucanase which
      rapidly hydrolysed cellotriose. Cel45Acore did not show activity on any of the
      three studied cello-oligosaccharides. The four endoglucanases' capacity to
      hydrolyse beta-glucan and glucomannan were studied. Cel12A hydrolysed beta-glucan
      and glucomannan slightly less compared with Cel5A and Cel7B. Cel45A was able to
      hydrolyse glucomannan significantly more compared with beta-glucan. The
      capability of Cel45A to hydrolyse glucomannan was higher than that observed for
      Cel12A, Cel5A and Cel7B. The results indicate that Cel45A is a glucomannanase
      rather than a strict endoglucanase.

PMID- 12204559
TI  - The alanine racemase gene alr is an alternative to antibiotic resistance genes in
      cloning systems for industrial Corynebacterium glutamicum strains.
AB  - The potential of the alanine racemase gene alr from Corynebacterium glutamicum
      ATCC 13032 to substitute for antibiotic resistance determinants in cloning
      systems has been investigated. The alr gene was identified by a PCR technique and
      its nucleotide sequence was determined. The deduced protein revealed the highest
      amino acid sequence similarity to the Alr protein from Mycobacterium smegmatis
      with 45% identical and 58% similar amino acids. A defined alr deletion mutant of
      C. glutamicum displayed a strict dependence on the presence of D-alanine for
      growth on complex and minimal medium. The alr gene was placed on a novel C.
      glutamicum vector which is completely free of antibiotic resistance genes. In
      vivo complementation of the chromosomal alr deletion with alr-carrying vectors
      permitted growth of the mutant strain in the absence of external D-alanine and
      provided strong selective pressure to maintain the plasmid. The alr gene enabled
      the selection of C. glutamicum transformants with a similar efficiency as the
      tetracycline resistance gene tetA(33). These data provided experimental evidence
      that the alr gene can be applied as an alternative selection marker to antibiotic
      resistance genes in industrial C. glutamicum strains. In an application example,
      the novel deltaalr host-alr(+) vector-system for C. glutamicum was used to
      overproduce the vitamin D-pantothenic acid.

PMID- 12204560
TI  - Shape imposed by secondary structure of a polypeptide affects its free diffusion
      through liquid-filled pores.
AB  - The purpose of the present study was to investigate the effect of secondary
      structure of three model polypeptides on their apparent permeability (P(app))
      across a synthetic, microporous membrane. Poly-L-lysine (PL), poly-L-glutamate
      (PGlu), and poly-L-lysine-L-phenylalanine (1:1) (PLP) were selected because a
      solution environment in which their predominant secondary structure is random
      coil (RC), alpha-helix, and beta-sheet, respectively, is easily achieved. The
      conformation of each polypeptide was verified by circular dichroism (CD).
      Diffusion studies were conducted under sink conditions at 25 degrees C across a
      microporous polyester membrane using a donor concentration of 0.02 mM for each
      model polypeptide. NMR was utilized to obtain a second estimation of the
      diffusion coefficient for each polypeptide. The equivalent hydrodynamic radii
      (R(e)) of the three model polypeptides were calculated using the values of the
      diffusion coefficient obtained by both NMR and the classic in vitro diffusion
      studies. The viscosity of each polypeptide solution was also determined to
      investigate the effect of viscosity on the aqueous diffusion coefficient.
      Statistical analysis demonstrated a significant (P < 0.05) difference in both
      P(app) and the aqueous diffusion coefficient (D(aq)), as well as the calculated
      R(e) values, between all three model polypeptides and there was no significant (P
      > 0.05) difference in the viscosity of the polypeptide solutions. Values of D(aq)
      and R(e) calculated from the diffusion studies were in relatively close agreement
      to those obtained using NMR. The logarithm of P(app) was highly correlated (r = 
      0.961) with the values of R(e) calculated from NMR (R(e (NMR))) rather than the
      mw of the polypeptides (r = 0.681). Values of the Perrin or shape factor which
      deviate substantially from unity are suggestive of a non-spherical or ellipsoid
      shape and were 1.22 +/- 0.20, 1.55 +/- 0.11, and 2.38 +/- 0.20 for PGlu, PL, and
      PLP, respectively. In conclusion, the observed difference in the membrane
      transport/diffusion of the three model polypeptides is suggested to be due to the
      shape associated with the secondary structure of each macromolecule, rather than
      the polypeptide's mw or the viscosity of the dilute polypeptide solution.

PMID- 12204561
TI  - Design of naltrexone-loaded hydrolyzable crosslinked nanoparticles.
AB  - A hydrolyzable crosslinker (N,O-dimethacryloylhydroxylamine (MANHOMA)) was
      synthesized by a modified method and was characterized using 1H-NMR, FTIR, and
      melting point determination. Naltrexone-loaded nanoparticles were prepared by
      copolymerization of poly(ethylene glycol)1000 monomethyl ether mono methacrylate
      (PEO-MA), methyl methacrylate (MMA) and N,O-dimethacryloylhydroxylamine (MANHOMA)
      in 0.4% poly(vinyl alcohol) aqueous solution. The nanoparticles were
      characterized by FTIR, particle size determination and transmission electron
      microscope (TEM). The TEM photomicrographs of the nanoparticles show a
      crosslinked core surrounded by a ring formed by the polyethylene glycol tail of
      PEO-MA. The loading efficiency of the nanoparticles and in vitro drug
      availability from the nanoparticles were investigated. The naltrexone-loaded
      hydrolyzable crosslinked nanoparticles were able to sustain the release of
      naltrexone for different periods of time, depending on the monomer feed
      composition.

PMID- 12204562
TI  - Lecithin microemulsions for the topical administration of ketoprofen:
      percutaneous adsorption through human skin and in vivo human skin tolerability.
AB  - The potential application of highly biocompatible o/w microemulsions as topical
      drug carrier systems for the percutaneous delivery of anti-inflammatory drugs,
      i.e. ketoprofen, was investigated. Microemulsions were made up of triglycerides
      as oil phase, a mixture of lecithin and n-butanol as a surfactant/co-surfactant
      system and an aqueous solution as the external phase. To evaluate the
      percutaneous enhancing effect of oleic acid, this compound was used as a
      component of some o/w microemulsions. The topical carrier potentialities of
      lecithin-based o/w microemulsions were compared with respect to conventional
      formulations, i.e. a w/o emulsion, a o/w emulsion and a gel. Physicochemical
      characterisation of microemulsions was carried out by light scattering and zeta
      potential analyses. Microemulsions showed mean droplet size < 35 nm and a
      negative zeta potential, that is -39.5 mV for the oleic acid-lecithin
      microemulsion and -19.7 mV for the lecithin-based microemulsion. The percutaneous
      adsorption of the various topical formulations was evaluated through healthy
      adult human skin, which was obtained from abdominal reduction surgery. Ketoprofen
      loaded microemulsions showed an enhanced permeation through human skin with
      respect to conventional formulations. No significant percutaneous enhancer effect
      was observed for ketoprofen-loaded oleic acid-lecithin microemulsions. The human
      skin tolerability of various microemulsion formulations was evaluated on human
      volunteers. Microemulsions showed a good human skin tolerability.

PMID- 12204563
TI  - Preparation and structural investigations of colloidal dispersions prepared from
      cubic monoglyceride-water phases.
AB  - Dispersions of bicontinuous cubic monoglyceride-water phases, so-called
      'cubosomes', have been proposed as parenteral sustained release delivery systems.
      For the present study, dispersions of monoolein-rich monoglycerides (MO), with or
      without purified soya phospholipids (PL), were prepared by equilibration of a
      MO/(PL)/water cubic phase, subsequent fragmentation with a poloxamer 407 (P407)
      solution, sonication and homogenization. This yielded systems of very different
      macroscopic appearance: Almost transparent dispersions, slightly turbid systems,
      opaque dispersions or milky emulsions. The mean z-average particle diameters
      ranged from 80 nm to well above 350 nm. Considerable particle growth could be
      detected in most systems during storage at room temperature. Storage at 5 degrees
      C resulted in the formation of ointment-like gels, which may be attributed to the
      crystallization of MO. Freeze-fracture transmission electron micrographs of MO
      dispersions revealed predominantly spherical particles with a low fracturing
      tendency. Synchrotron radiation X-ray diffraction indicated that high energy
      input during disintegration of the cubic phase leads to very complex systems in
      which particles with a cubic structure and MO/(PL) vesicles may coexist. The
      characteristic reflections of cubic systems were absent in the diffraction
      patterns of almost transparent or slightly turbid dispersions. The results
      indicate a strong dependence of ultrastructure of the dispersions on the
      preparation parameters.

PMID- 12204564
TI  - Crystal habit and tableting behavior.
AB  - The tableting behavior of drugs can be affected by changes in the crystal habit.
      Different crystal habits of the common analgesic drugs ibuprofen and
      acetaminophen were prepared. Their tableting behavior was characterized. In the
      case of ibuprofen, a plate-shaped crystal was compared with the common needle
      shaped form. In the case of acetaminophen, plate-shaped and prismatic crystals of
      two different particle sizes were prepared. The aim was to find a crystal form
      that is suitable for direct compression with only a low amount of excipients.
      This requires a substance that forms stable compacts at low punch forces, having
      a good flowability and only a low tendency to stick to the punches. In order to
      compare the tableting behavior of different substances, a comparative factor (T
      factor) was calculated, based on typical parts of the punch force/displacement
      profile and properties of the resulting compact. This method works with low
      amounts of substance and allows a rapid reproducible determination of the
      tableting behavior. The method was evaluated by characterizing different typical
      excipients normally used for the production of tablets.

PMID- 12204565
TI  - Albumin nanoparticles as carriers for a phosphodiester oligonucleotide.
AB  - The goal of this study was the evaluation of albumin nanoparticles as drug
      delivery systems for antisense oligonucleotides. Bovine serum albumin (BSA)
      nanoparticles were prepared by a coacervation process. A phosphodiester
      oligonucleotide was either incorporated into the matrix of the particles by
      incubation with the albumin prior the coacervation process or adsorbed onto the
      pre-formed nanoparticles. Incorporated and/or adsorbed oligonucleotide was
      estimated by capillary electrophoresis and fluorescence spectroscopy. The
      adsorbed amount of oligonucleotide was dramatically dependent on the pH of the
      medium. Desorption of the oligonucleotide was also affected by the pH and ionic
      strength of the medium. This indicated that electrostatic forces play a major
      role in the interaction between the oligonucleotide and the nanoparticles. When
      the oligonucleotide was incubated with the albumin prior to nanoparticle
      formation, the profile of release confirmed that a fraction was incorporated into
      the matrix and its release was controlled by the albumin degradation. The
      hybridisation capability of the oligonucleotide in both nanoparticle formulations
      was retained. However, only the oligonucleotide incorporated into the
      nanoparticle matrix was protected against enzymatic degradation.

PMID- 12204566
TI  - Studies on a high encapsulation of colchicine by a niosome system.
AB  - To prepare niosomes which have high encapsulation capacity for soluble drugs,
      starting from Span 60 and cholesterol, an improved method, evaporation-sonication
      method, was proposed. The corresponding niosomes show a good stability at least
      40 days. Colchicine was chosen as a model drug for examining the capsulation
      capacity of these niosomes. To obtain the highest encapsulation efficiency,
      several factors including the structure of surfactant, level of lipid, content of
      drug and cholesterol were investigated and optimized. The inner cause was also
      discussed. The results indicate that the Span 60 is the most ideal surfactant
      among four kinds of Span. Furthermore, the release studies of colchicine and 5
      fluorouracil (5-FU) in vitro from niosomes exhibited a prolonged release profile
      as studied over a period of 24 h. The results demonstrated that niosomes prepared
      in this way not only have high encapsulation capacity but also is expected that
      side effects of drugs may be reduced. It still suggests that this method may be
      used extensively in the field of encapsulation soluble drugs.

PMID- 12204567
TI  - Effect of plasticizer on the dynamic surface tension and the free volume of
      Eudragit systems.
AB  - The purpose of the present study was to determine the changes of dynamic surface
      tension of aqueous Eudragit dispersions quantitatively and compare these data
      with the free volume of the free films formed from several dispersions of
      different dibutyl sebacate (DBS) concentrations. Eudragit L 30D and Eudragit RL
      30D aqueous colloidal polymer dispersions and their cast free films were
      examined. The concentration of DBS varied in the dispersions from 0 to 20%. The
      dynamic surface tension of the dispersions were measured by the Du Nouy ring
      method while the free volume of cast films were determined by positron
      annihilation spectroscopy. The obtained results show that dynamic surface tension
      measurements indicate the white point (WP) of Eudragit dispersions by a
      significant standard deviation increase. This may suggest the applicability of
      dynamic surface tension measurements for the determination of the WP of polymeric
      dispersions. A decrease in the WP temperature of Eudragit dispersions with an
      increasing plasticizer concentration was observed up to the DBS concentration of
      10% w/w. Above this concentration neither the WP of the polymer dispersion nor
      the free volume of the free films of the polymer were changed remarkably.

PMID- 12204568
TI  - Physical stability of solid dispersions of the antiviral agent UC-781 with PEG
      6000, Gelucire 44/14 and PVP K30.
AB  - This paper describes the physical stability of solid dispersions of UC-781 with
      PEG 6000, Gelucire 44/14 and PVP K30 prepared by the solvent and melting methods.
      The concentration of the drug in the solid dispersions ranged from 5 to 80% w/w.
      The solid dispersions were stored at 4-8 and 25 degrees C (25% RH), then their
      physicochemical properties were analysed by differential scanning calorimetry
      (DSC), X-ray powder diffraction and dissolution studies as a function of storage
      time. The DSC curves of solid dispersions of UC-781 with PVP K30 did not show any
      melting peaks corresponding to UC-781 after storage, indicating no
      recrystallization of the drug. The DSC data obtained from PEG 6000 and Gelucire
      44/14 showed some variations in melting peak temperatures and enthalpy of fusion
      of the carriers. It was shown that the enthalpy of fusion of PEG 6000 in the
      dispersions increased after storage; it was more pronounced for samples stored at
      25 degrees C compared to those at 4-8 degrees C indicating the reorganization of
      the crystalline domains of the polymer. Similarly, the enthalpy of fusion of
      Gelucire 44/14 in the solid dispersions increased as a function of time.
      Dissolution of UC-781 from all solid dispersions decreased as a function of
      storage time. While these observations concurred with the DSC data for all solid
      dispersions, they were not reflected by X-ray powder diffraction data. It was
      concluded that it is the change of the physical state of the carriers and not
      that of the drug, which is responsible for the decreased dissolution properties
      of the solid dispersions investigated.

PMID- 12204569
TI  - Solubilization and preformulation of carbendazim.
AB  - The solubilization of carbendazim by pH in combination with cosolvents,
      surfactants or complexants was investigated. At pH 7 the total drug solubility is
      6.11 +/- 0.45 microg/ml which increases by 1-7 fold with cosolvent, surfactant or
      complexant. However, at pH 2 the solubility increases by 250 times. Cosolvents
      have a negligible effect (50% increase) on the total drug solubility at pH 2
      because of the high polarity of the cationic drug. Also pH combined with nonionic
      surfactants does not improve solubility, as relatively less polar micelles are
      not able to accommodate the cationic drug. Interestingly, the total drug
      solubility increases by combining pH 2 with complexants, as they can form a
      complex with the isolated aromatic ring of both the unionized and the ionized
      drug. The proposed oral formulation of 1 mg/ml carbendazim at pH 2 does not
      precipitate in the presence of Seven Up or water. But it does precipitate with pH
      7 buffer when diluted 1:10 but not 1:100 or 1:250.

PMID- 12204570
TI  - Size-dependency of nanoparticle-mediated gene transfection: studies with
      fractionated nanoparticles.
AB  - Nanoparticles formulated from biodegradable polymers such as poly (lactic acid)
      and poly (D,L-lactide-co-glycolide) (PLGA) are being extensively investigated as
      non-viral gene delivery systems due to their sustained release characteristics
      and biocompatibility. PLGA nanoparticles for DNA delivery are mainly formulated
      using an emulsion-solvent evaporation technique. However, this formulation
      procedure results in the formation of particles with heterogeneous size
      distribution. The objective of the present study was to determine the relative
      transfectivity of the smaller- and the larger-sized fractions of nanoparticles in
      cell culture. PLGA nanoparticles containing a plasmid DNA encoding luciferase
      protein as a marker were formulated by a multiple emulsion-solvent evaporation
      method (mean particle diameter = 97 +/- 3 nm) and were fractionated using a
      membrane (pore size: 100 nm) filtration technique. The particles that passed
      through the membrane were designated as the smaller-sized nanoparticles (mean
      diameter = 70 +/- 2 nm) and the fraction that was retained on the membrane as the
      larger-sized nanoparticles (mean diameter = 202 +/- 9 nm). The smaller-sized
      nanoparticles showed a 27-fold higher transfection than the larger-sized
      nanoparticles in COS-7 cell line and a 4-fold higher transfection in HEK-293 cell
      line. The surface charge (zeta potential), cellular uptake, and the DNA release
      were almost similar for the two fractions of nanoparticles, suggesting that some
      other yet unknown factor(s) is responsible for the observed differences in the
      transfection levels. The results suggest that the particle size is an important
      factor, and that the smaller-sized fraction of the nanoparticle formulation
      predominantly contributes towards their transfection.

PMID- 12204571
TI  - Alginate-konjac glucomannan-chitosan beads as controlled release matrix.
AB  - Controlled release beads were prepared by using alginate (ALG), konjac
      glucomannan (KGM) and chitosan (CHI). Bovine serum albumin and insulin were used
      as model proteins for in vitro assessments. It was observed that KGM could be
      contained within beads, and faintness hydrogen binding and electrostatic
      interaction exist between ALG and KGM by infrared spectra. Clear dents were found
      on the surface of beads using KGM by scanning electron microscopy. Use of KGM
      could help increase the payload of drug. After beads were treated by 0.1 N HCl
      for 4 h and put into pH 7.4 buffers, protein was released from ALG-CHI beads
      within 1 h, while it was lost from ALG-KGM-CHI beads for 3 h. However, the
      leaking of protein from ALG-KGM-CHI beads was also increased in 0.1 N HCl
      solution. Concentration of gelling ion had great effect on release rate and gel
      structure. Studies of water of hydration had shown that swelling of ALG-KGM-CHI
      beads was higher than that of ALG-CHI beads in acidic solution, but the opposite
      result was obtained in alkali solution. The result indicated that the diffusion
      of protein was related to the viscosity and swelling properties of KGM.

PMID- 12204572
TI  - Studies of curcumin and curcuminoids. XXVII. Cyclodextrin complexation:
      solubility, chemical and photochemical stability.
AB  - Cyclodextrin complexes of the natural compound curcumin were prepared in order to
      improve the water solubility and the hydrolytic and photochemical stability of
      the compound. Complex formation resulted in an increase in water solubility at pH
      5 by a factor of at least 10(4). The hydrolytic stability of curcumin under
      alkaline conditions was strongly improved by complex formation, while the
      photodecomposition rate was increased compared to a curcumin solution in organic
      solvents. The cavity size and the charge and bulkiness of the cyclodextrin side
      chains influenced the stability constant for complexation and the degradation
      rate of the curcumin molecule.

PMID- 12204573
TI  - A comparison between the protection of LDH during freeze-thawing by PEG 6000 and
      Brij 35 at low concentrations.
AB  - The protection of lactate dehydrogenase (LDH) by low concentrations of the non
      surface-active polyethylene glycol (PEG 6000) or the non-ionic surfactant PEG
      dodecyl ether (Brij 35) was investigated during freeze-thawing. The freeze
      thawing process was performed with a controlled temperature history, and the
      protective mechanisms were elaborated. The systems were examined by differential
      scanning calorimetry (DSC), fluorescence spectroscopy and surface tension
      measurements. LDH activity assays were performed spectrophotometrically. Very low
      concentrations of PEG 6000 (8 x 10(-5) mM) or Brij 35 (4 x 10(-3) mM) protected
      LDH during freeze-thawing with a low cooling rate. With an increased freezing
      rate, higher concentrations of the additives were needed for full protection. No
      interaction was detected between LDH and Brij molecules. The strong interaction
      between LDH and PEG molecules disappeared with a small change in the protein
      structure, using a hybrid of LDH. The protein was nevertheless completely
      protected. The amount of Brij required for complete protection at high cooling
      rates correlated with the created ice surface area. The protection by PEG
      indicated a certain correlation with the ice crystal size and with the formation
      of a PEG hydrate. Brij or PEG hydrate molecules might compete with the protein
      for adsorption at the ice surface and thereby protect the protein during freeze
      thawing.

PMID- 12204574
TI  - Evaluation of controlled-release polar lipid microparticles.
AB  - The aim of the present study was to prepare controlled-release tablets of poorly
      soluble drug, felodipine, and various erodable lipophilic excipients. Spray
      chilling was used to formulate the drug and the excipients into solid dispersion
      microparticles, which were then compressed. The microparticles were characterised
      by Fourier transform infrared spectroscopy, hot-stage microscopy, scanning
      electron microscopy, and image analysis. The amine and the carbonyl groups of
      felodipine formed hydrogen bonds with the carriers. The shape of the particles
      was spherical with the median particle diameter ranging from 25 to 35 microm.
      Surprisingly, the degree of crystallinity in felodipine and the ease of tablet
      disintegration played a more significant role on the felodipine dissolution rate
      than the matrix lipophilicity. Felodipine release rate was slowest from the least
      lipophilic tablets.

PMID- 12204575
TI  - A comparison between the use of dynamic mechanical analysis and oscillatory shear
      rheometry for the characterisation of hydrogels.
AB  - In this study the use of dynamic mechanical analysis (DMA) for the mechanical
      characterisation of pharmaceutical hydrogels was evaluated. DMA was used in two
      different modes, the "controlled force" and the "multi-strain" (MS). The results
      obtained on dextran methacrylate hydrogels of various compositions were compared
      to those obtained using an oscillatory shear rheometer. The best agreement was
      found between the MS-DMA and the rheometer results. The moduli measured in MS-DMA
      were extrapolated towards zero compression to obtain the modulus of the
      hydrogels. This procedure resulted in good agreement with the data obtained with
      the rheometer. Hydrogels were analysed after swelling to equilibrium with both
      methods, DMA and rheology. A scaling between the elastic modulus (G') and the
      equilibrium swollen polymer volume fraction (v(2,s)) could be found, although the
      best correlation between G' and v(2,s) was obtained with the rheometer.

PMID- 12204576
TI  - Kinetics of the radicals induced in gamma-irradiated naproxen sodium and apranax.
      Applicability of ESR technique to monitor radiosterilization of naproxen sodium
      containing drugs.
AB  - In the present work the spectroscopic and kinetic features of the radicals
      induced in gamma-irradiated naproxen sodium (NS) and apranax (AP) tablet are
      investigated at room and different temperatures in the dose range of 2.5-25 kGy
      by electron spin resonance technique (ESR). Radiation produces two different
      radicals (I, II) in NS quite stable at room temperature but relatively unstable
      above room temperature, giving rise to a broad singlet centered at g = 2.0057.
      Dose-response and decay curves associated with the broad singlet were found to
      follow bi-exponentials. Information concerning the saturation decay rates and
      activation energies were obtained through the characteristics of these
      exponentials. Similar calculations were also performed for AP, which contains 550
      mg NS as active ingredient, and the applicability of ESR technique for monitoring
      radiosterilization of AP was discussed.

PMID- 12204577
TI  - Lipoyl dehydrogenase catalyzes reduction of nitrated DNA and protein adducts
      using dihydrolipoic acid or ubiquinol as the cofactor.
AB  - Inflamed tissues generate reactive nitrogen oxide species (RNO(x)), such as
      peroxynitrite (ONOO-)and nitryl chloride (NO2Cl), which lead to formation of
      nitrated DNA and protein adducts, including 8-nitroguanine (8NG), 8-nitroxanthine
      (8NX), and 3-nitrotyrosine (3NT). Once formed, the two nitrated DNA adducts are
      not stable in DNA and undergo spontaneous depurination. Nitration of protein
      tyrosine leads to inactivation of protein functions and 3NT has been detected in
      various disease states. We herein report that reduction of these nitro adducts to
      their corresponding amino analogues can be catalyzed by lipoyl dehydrogenases (EC
      1.8.1.4) from Clostridium kluyveri (ck) and from porcine heart (ph) using NAD(P)H
      as the cofactor. We also found that dihydrolipoic acid (DHLA) and ubiquinol can
      be used as effective cofactors for reduction of 8NG, 8NX, and 3NT by these lipoyl
      dehydrogenases. The reduction efficiency of the mammalian enzyme is higher than
      the bacterial isozyme. The preference of cofactors by both lipoyl dehydrogenases
      is DHLA>NAD(P)H>ubiquinol. In all the systems examined, the nitrated purines are
      reduced to a greater extent than 3NT under the same conditions. We also
      demonstrate that this lipoyl dehydrogenase/antioxidant system is effective in
      reducing nitrated purine on NO2Cl-treated double stranded calf thymus DNA, and
      thus decreases apurinic site formation. The nitroreductase activity for lipoyl
      dehydrogenase might represent a possible metabolic pathway to reverse the process
      of biological nitration.

PMID- 12204578
TI  - Cytotoxicity and DNA damage induced by a new platinum(II) complex with pyridine
      and dithiocarbamate.
AB  - A new platinum(II) complex containing a pyridine nucleus and a dithiocarbamate
      moiety as ligands ([Pt(ESDT)(Py)Cl]) was evaluated for in vitro cytotoxicity in
      the cisplatin-sensitive human ovarian 2008 and in the isogenic-resistant C13*
      cell lines. In both cell types, a tumor cell growth inhibition greater than
      cisplatin and a complete lack of cross-resistance in C13* cells were found.
      Despite its molecular size, [Pt(ESDT)(Py)Cl] accumulation was much higher than
      cisplatin both in parent and resistant cells. Studying the mechanism of action in
      cell-free media, we established that [Pt(ESDT)(Py)Cl] more efficiently interacts
      with DNA in vitro compared to cisplatin maintaining a binding preference for GG
      rich sequences of DNA. On the contrary, DNA platination in vivo by
      [Pt(ESDT)(Py)Cl] was found lower than cisplatin. An analysis of the type of DNA
      lesions induced by [Pt(ESDT)(Py)Cl] suggests that the cytotoxic efficacy and the
      ability to overcome cisplatin resistance seem to be related to a different
      mechanism of interaction with DNA and/or with other key cellular components.

PMID- 12204580
TI  - Tissue distribution of cytosolic beta-elimination reactions of selenocysteine Se
      conjugates in rat and human.
AB  - Selenocysteine Se-conjugates (e.g. methylselenocysteine) have been shown to be
      potent chemopreventive and chemoprotective agents, and inducers of apoptosis.
      Although the mechanism of action remains to be elucidated, beta-elimination of
      these compounds by beta-lyase enzymes into corresponding selenols, pyruvate and
      ammonia is thought to be critical. This study describes in vitro beta-lyase
      activity in nine rat organs using three selenocysteine Se-conjugates and S-(2
      chloro-1,1,2-trifluoroethyl)-L-cysteine. For all substrates the highest beta
      elimination rates were found in kidney, followed by liver, while brain, spleen,
      heart, large and small intestine, thyroid and lung were of minor importance.
      Since liver plays an important role in beta-elimination, hepatic beta-lyase
      activity was extensively studied using 23 selenocysteine Se-conjugates and S-(2
      chloro-1,1,2-trifluoroethyl)-L-cysteine and was compared with previously obtained
      renal beta-lyase data. The results showed that hepatic beta-lyase activities were
      4-25-fold lower than the corresponding renal beta-lyase activities. Hepatic beta
      elimination of the substrates appeared to be exclusively catalyzed by the
      pyridoxal 5'-phosphate-dependent beta-lyase enzyme kynureninase. Studies
      performed with human hepatic cytosols of three individuals showed that hepatic
      beta-lyase activity was 2-5-fold higher when compared with the previously
      obtained human renal activity. Significant correlation was obtained between human
      hepatic beta-lyase activities of three individuals. The relevance of this data
      for using SeCys-conjugates as chemopreventive and a chemoprotective agent is
      discussed. Based on the large differences in organ-selective beta-elimination and
      specific beta-lyase activity between rat and humans, the rat might not be a good
      model to investigate nephrotoxicity of cysteine S-conjugates, and chemoprevention
      and chemoprotection of SeCys-conjugates in man.

PMID- 12204579
TI  - DNA adduct formation from quaternary benzo[c]phenanthridine alkaloids
      sanguinarine and chelerythrine as revealed by the 32P-postlabeling technique.
AB  - Using the 32P-postlabeling assay, we investigated the ability of quaternary
      benzo[c]phenanthridine alkaloids, sanguinarine, chelerythrine and fagaronine, to
      form DNA adducts in vitro. Two enhanced versions of the assay (enrichment by
      nuclease P1 and 1-butanol extraction) were utilized in the study. Hepatic
      microsomes of rats pre-treated with beta-naphthoflavone or those of uninduced
      rats, used as metabolic activators, were incubated in the presence of calf thymus
      DNA and the alkaloids, with NADPH used as a cofactor. Under these conditions
      sanguinarine and chelerythrine, but not fagaronine, formed DNA adducts detectable
      by 32P-postlabeling. DNA adduct formation by both alkaloids was found to be
      concentration dependent. When analyzing different atomic and bond indices of the
      C11-C12 bond (ring B) in alkaloid molecules we found that fagaronine behaved
      differently from sanguinarine and chelerythrine. While sanguinarine and
      chelerythrine showed a preference for electrophilic attack indicating higher
      potential to be activated by cytochrome P450, fagaronine exhibited a tendency for
      nucleophilic attack. Our results demonstrate that sanguinarine and chelerythrine
      are metabolized by hepatic microsomes to species, which generate DNA adducts.

PMID- 12204581
TI  - The effect of Au injection on the ceruloplasmin, metallothionein and 8
      hydroxydeoxyguanosine of rat serum, kidney and liver.
AB  - The present study was carried out to investigate the effect of gold (Au)
      injection on copper (Cu) and two types of ceruloplasmin (Cp), total Cp (ID1) and
      active Cp (ID2), metallothionein (MT) in the serum, kidney and liver, and 8
      hydroxydeoxyguanosine (8-OHdG) in the rat kidney. The Cu contents in sera and
      kidneys of Au-injected rats were 1.7 and 5.5 times higher than those in sera and
      kidneys of control rats, respectively. The most of Cu in the sera of the control
      rats or Au-injected rats were observed in the Cp fractions from a Sephacryl S-200
      column. The Cu concentration in the Cp fractions was increased by Au injection.
      Significant increases of ID1 and ID2 were found in the sera of the control rats
      and Au-injected rats, while there was no significant difference in those
      concentrations of livers or kidneys between the control rats and Au-injected
      rats. Our results indicated that the most of Cp existed as active ID1. The
      immunoreactivity of 8-OHdG was located in the cortex of the Au-injected rat.
      These results indicated that the oxidative DNA damage occurred in the renal
      cortex of the Au-injected rat and the localization of DNA damage did not coincide
      with that of Cu-MT. These findings suggest that the oxidative DNA damage in the
      kidneys of rats injected with Au is associated with Cu except Cu-MT.

PMID- 12204582
TI  - Acrylonitrile irreversibly inactivates glyceraldehyde-3-phosphate dehydrogenase
      by alkylating the catalytically active cysteine 149.
AB  - Acrylonitrile (AN) is a vinyl monomer used in the production of synthetic fibers,
      rubber and plastics. AN is acutely toxic but its mechanism of toxicity remains to
      be established. AN is metabolized to cyanide in vivo but cyanide production alone
      cannot explain acute AN toxicity. Previous work in our laboratory has shown that
      AN can alkylate highly reactive cysteine residues in proteins. Glyceraldehyde-3
      phosphate dehydrogenase (GAPDH), a critical enzyme involved in glycolysis, has a
      catalytically active cysteine 149 in its active site. We report that AN
      irreversibly inhibits GAPDH with second-order rate constants, at pH 7.4, of 3.7
      and 9.2 M(-1) s(-1) at 25 and 37 degrees C, respectively. A combination of matrix
      assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF)
      and electrospray ionization-mass spectrometry-mass spectrometry (ESI-MS-MS) was
      used to show that AN inactivates GAPDH by covalently binding to cysteine 149 in
      the active site of the enzyme. Inactivation of GAPDH by AN would be expected to
      impair glycolytic ATP production and when coupled with the inhibition of
      mitochondrial ATP synthesis by the AN metabolite cyanide would result in
      metabolic arrest. The brain can withstand metabolic arrest for only a few minutes
      thus these combined actions may account for the acute toxicity of AN in vivo.

PMID- 12204583
TI  - Apparent toxicity resulting from the sequestering of nutrient trace metals during
      standard Selenastrum capricornutum toxicity tests.
AB  - The water accommodated fractions (WAFs) of aqueous mixtures of three lubricant
      additives showed significant apparent toxicity to the freshwater alga,
      Selenastrum capricornutum, and experiments were conducted to investigate the
      hypothesis that toxicity resulted from the removal of one or more essential
      nutrients from the test medium by the lubricant additives. Algal growth effects
      were noted at ashless dispersant A concentrations as low as 0.5 x mg l(-1) and
      growth was completely inhibited at 100 mg x l(-1). Algal cells transferred from
      the 100 mg x l(-1) WAF of ashless dispersant A to fresh medium at the end of a
      standard 96-h toxicity test resumed growing at a rate similar to growth in
      undosed algal medium, indicating that the effect was algistatic rather than
      algicidal. Fortifying the iron (Fe) and disodium ethylenediaminetetraacetic acid
      (EDTA) concentrations of the WAF with 200% of the concentrations used in the
      formulation of algal medium after 24 h of exposure caused a resumption of algal
      growth at a rate comparable to the control growth, and a resulting EL50 value
      above 100 mg x l(-1). Similar effects were observed when the two other lubricant
      additives were tested at WAF concentrations that completely inhibited algal
      growth during standard toxicity tests: fortification of a 50 mg x l(-1) WAF of
      ZnDTP with 1000% of the Fe and EDTA used in the formulation of algal medium
      caused a resumption of growth at a rate statistically identical to the control
      growth, and the fortification of a 2800 mg x l(-1) WAF of ashless dispersant B
      with 700% of the entire complement of nutrients used in the formulation of algal
      medium caused a resumption of growth at a rate comparable to the control. The
      indirect toxic effect of these lubricant additives to algae results from the
      sequestration of one or more nutrient metals essential for algal growth. Standard
      algal toxicity tests with these lubricant additives may, therefore, have little
      environmental relevance because the complex chemistry of natural waters differs
      greatly from the nutrient limited algal medium, and the sequestration effect
      observed in these static tests could be absent under real world conditions.

PMID- 12204584
TI  - Expression of P-glycoprotein and cytochrome p450 1A in intertidal fish
      (Anoplarchus purpurescens) exposed to environmental contaminants.
AB  - Whether P-glycoproteins (P-gps) like those which confer multidrug resistance in
      tumor cell lines are important in adaptation to chemicals in natural populations
      of vertebrates exposed to contaminant mixtures is the focus of this study. P-gp
      expression was examined in the intertidal fish high cockscomb blenny (Anoplarchus
      purpurescens) exposed to crude oil or pulp mill effluent. The relationship
      between P-gp expression and cytochrome p450 1A (CYP1A) induction also was
      investigated. Immunohistochemical (IHC) analysis revealed that levels of P-gp
      expression in the bile canaliculi were three- to five-fold greater in oil exposed
      fish than in control fish. Levels of P-gp expression were highly correlated with
      hepatic CYP1A levels previously measured in these fish. In fish from sites near
      pulp mills, P-gp expression in freshly caught fish did not correlate with
      proximity to pulp mills. However, hepatic P-gp expression levels in freshly
      caught fish were 14-fold higher than in fish from those sites that were depurated
      in clean water for 6 weeks. CYP1A levels were also elevated in liver of freshly
      caught as compared with depurated fish. Expression of neither CYP1A nor P-gp was
      elevated in depurated fish exposed to sediment and food from within the original
      pulp mill effluent stream. Depurated fish, which were injected with the aryl
      hydrocarbon receptor (AHR) agonist ss-naphthoflavone (BNF) showed an expected
      induction of CYP1A but no induction of P-gp. These results suggest that in
      blennies, unlike CYP1A, P-gp expression is not regulated by the AHR pathway;
      although P-gp and CYP1A both may be induced by some compounds in petroleum and
      unidentified xenobiotics at field sites. While our data indicate that CYP1A and P
      gp are not coordinately regulated, these proteins may play complementary roles in
      cellular detoxification. Thus the elevation of P-gp activity may be an important
      mechanism of multixenobiotic resistance for organisms, such as intertidal fish,
      which are commonly exposed to anthropogenic contaminants and naturally occurring
      toxins.

PMID- 12204585
TI  - Physiological and cytological responses of the marine diatom Skeletonema costatum
      to 2,4-dichlorophenol.
AB  - Physiological and cytological responses of the marine diatom, Skeletonema
      costatum, to 2,4-dichlorophenol (2,4-DCP) were investigated after exposing algal
      cultures to 1-6 mg x l(-1) of 2,4-DCP for 96 h. Growth rate of the diatom was
      significantly reduced by 2,4-DCP at and above 3.0 mg x l(-1) while other
      biological parameters such as photosynthetic and respiration rates, carotenoid
      and protein content, ATP level and adenylate energy charge were unaffected.
      Exposure to 6.0 mg x l(-1) 2,4-DCP for 96 h resulted in the total lipid content
      being increased to 304%, while the RNA/DNA ratio was reduced to 31% of the
      control values. A parallel study by transmission electron microscopy further
      confirmed the increase in cellular lipid content, as evidenced by the
      accumulation of lipid droplets within diatom cells. A slight increase in
      carbohydrate (+37.8%) and decrease in chlorophyll a (-20.4%) and total
      chlorophyll c (-14.4%) were also found at 6.0 mg x l(-1) 2,4-DCP. Although 2,4
      DCP is known to uncouple oxidative phosphorylation, our results show that energy
      production was not significantly inhibited at sublethal concentrations of 2,4
      DCP. The observed growth inhibition in S. costatum caused by 2,4-DCP was
      associated with an increase in energy storage and inhibition of protein
      synthesis, as indicated by a reduction in RNA/DNA ratio.

PMID- 12204586
TI  - Rainbow trout primary epidermal cell proliferation as an indicator of aquatic
      toxicity: an in vitro/in vivo exposure comparison.
AB  - Little or no work has been carried out on primary cell cultures in terms of
      cellular proliferation and toxicity studies. Cell proliferation represents one of
      the most relevant cellular functions. Anti-PCNA antibodies have aroused
      considerable interest recently as potential immunocytochemical markers of
      proliferation for use in toxicity studies. In this study, PCNA methodology, which
      was developed primarily for mammalian tissues, was adapted to rainbow trout
      (Oncorhynchus mykiss (R.)) primary cultured epidermal cells exposed in vivo i.e.
      whole animal exposures and in vitro for the study of the ecotoxicological
      potential of the aromatic amine, 2,4-dichloroaniline (2,4-DCA), a member of a
      little studied and widespread class of aquatic pollutants. There are many
      approaches to assess the proliferative activity of cells. Immunocytochemical
      methods offer a high sensitivity and specificity. The immunohistochemical avidin
      biotin complex (ABC) method was used for the detection and quantification of
      PCNA, one of the best-known endogenous proliferation markers, applying the
      mammalian monoclonal antibody PC-10 to formalin-fixed primary cultures of rainbow
      trout skin. Here we describe our experience with the immunocytochemical detection
      and quantification of this proliferation marker. Results indicate that the
      antibody cross reacts with the corresponding rainbow trout epitope and that the
      alterations in PCNA labelling in the in vivo and in vitro exposed cultures
      followed similar patterns. This paper presents data on the validation of rainbow
      trout primary epidermal culture as an in vitro ecotoxicity model with epidermal
      proliferation as an endpoint. It can be concluded that cellular proliferation
      could be used as an indicator of the aquatic toxicity potential of xenobiotics.
      Correlations between cellular proliferation responses in primary cultures derived
      from in vivo exposed rainbow trout and primary cultures exposed in vitro were
      assessed. A dose-response was evidenced in both approaches, however the in vivo
      exposures appeared to be approximately two orders of magnitude more sensitive
      than the in vitro exposures. Responses in vitro occurred between 200 and 1000
      micro M while in vivo responses were between 2 and 10 micro M. The good
      qualitative correspondence between the in vitro and in vivo results indicates
      that studies using trout epidermal cells allow the identification of xenobiotic
      effects in fish skin. However, further work is required before quantitative
      predictions i.e. effective concentrations in vivo, can be made from in vitro
      studies. This study suggests that the in vitro exposed rainbow trout primary
      cultured cell model with proliferation as an endpoint can be used as an
      alternative testing procedure to the whole animal assay.

PMID- 12204587
TI  - The effect of water hardness on the toxicity of uranium to a tropical freshwater
      alga Chlorella sp.
AB  - Uranium (U) derived from mining activities is of potential ecotoxicological
      concern to freshwater biota in tropical northern Australia. Few data are
      available on the effects of water hardness (Ca and/or Mg), which is elevated in U
      mine wastewaters, on the toxicity and bioavailability of U to freshwater biota,
      particularly algae. This study determined the effect of water hardness (8, 40,
      100 and 400 mg CaCO(3) x l(-1), added as calcium (Ca) and magnesium (Mg)
      sulphate) on the toxicity (72 h growth rate inhibition) of U to the unicellular
      green alga, Chlorella sp., in synthetic freshwater, at constant pH (7.0) and
      alkalinity (8 mg CaCO(3) x l(-1)), similar in chemical composition to sandy
      coastal streams in tropical northern Australia. A 50-fold increase in water
      hardness resulted in a 5-fold decrease (P<or =0.05) in the toxicity of U to
      Chlorella sp. (i.e. the 72 h EC(50) increased from 56 to 270 micro g U l(-1)).
      Possible explanation for the ameliorative effect of water hardness includes: (i)
      competition between U and Ca and/or Mg for binding sites on the cell surface; and
      (ii) a change in U speciation, and hence, bioavailability. Results showed that
      extracellular (cell-surface) and intracellular U concentrations significantly
      (P<0.05) decreased (2-5-fold) as water hardness increased from 8 to 400 mg
      CaCO(3)x l(-1). Calculation of U speciation using the geochemical model HARPHRQ
      showed that there were no significant (P>0.05) differences in the predicted
      speciation (% distribution) of U amongst the four water hardness levels. The
      reduction in U toxicity with increasing water hardness was most likely due to
      competition between U and Ca and/or Mg for binding sites on the algal cell
      surface. The minimum detectable effect concentrations of U were approximately 3
      and 24 times higher (at 8 and 400 mg CaCO(3)x l(-1) hardness, respectively) than
      the national interim U guideline value (0.5 micro g x l(-1)) for protecting
      aquatic ecosystems. Overall, the results reinforce the need for a more flexible U
      guideline based on a hardness-dependent algorithm, which may allow environmental
      managers to relax the national guideline for U on a site-specific basis.

PMID- 12204588
TI  - Effects of pH on survival, phosphorus concentration, adenylate energy charge and
      Na(+)-K(+) ATPase activities of Penaeus chinensis Osbeck juveniles.
AB  - Penaeus chinensis (Osbeck) juveniles were maintained for 14 days at pH 6.0, 7.0,
      7.6, 8.0 and 8.5, respectively. The effects of pH on survival, phosphorus
      concentration, adenylate energy charge (AEC) and Na(+)-K(+) adenosine
      triphosphatase (ATPase) activities of prawns were investigated. The results
      showed that survival of P. chinensis was impaired at low and high pH levels. The
      total phosphate level and AEC in abdominal muscle increased with pH level in
      range of 6.0-7.6 reaching the maximum values at pH 7.6. Thereafter, the levels
      declined with increasing pH level in range of 7.6-8.5. The change of Na(+)-K(+)
      ATPase activity in gill of prawn was similar to that of total phosphorus content
      and AEC in muscle of prawn at different pH. The effect of pH on Na(+)-K(+) ATPase
      activity in the muscle was lower than on that in gill.

PMID- 12204589
TI  - Genetic variability in sublethal tolerance to mixtures of cadmium and zinc in
      clones of Daphnia magna Straus.
AB  - To date, studies on genetic variability in the tolerance of aquatic biota to
      chemicals have focused on exposure to single chemicals. In the field, metals
      occur as elemental mixtures, and thus it is essential to study whether the
      genetic consequences of exposure to such mixtures differs from response to single
      chemicals. This study determined the feeding responses of three Daphnia magna
      Straus clones exposed to Cd and Zn, both individually and as mixtures. Tolerance
      to mixtures of Cd and Zn was expressed as the proportional feeding depression of
      D. magna to Cd at increasing zinc concentrations. A quantitative genetic analysis
      revealed that genotype and genotype x environmental factors governed population
      responses to mixtures of both metals. More specifically, genetic variation in
      tolerance to sublethal levels of Cd decreased at those Zn concentrations where
      there were no effects on feeding, and increased again at Zn concentrations that
      affected feeding. The existence of genotype x environmental interactions
      indicated that the genetic consequences of exposing D. magna to mixtures of Cd
      and Zn cannot be predicted from the animals' response to single metals alone.
      Therefore, current ecological risk assessment methodologies for predicting the
      effects of chemical mixtures may wish to incorporate the concept of genetic
      variability. Furthermore, exposure to low and moderate concentrations of Zn
      increased the sublethal tolerance to Cd. This induction of tolerance to Cd by Zn
      was also observed for D. magna fed algae pre-loaded with both metals.
      Furthermore, in only one clone, physiological acclimatization to zinc also
      induced tolerance to cadmium. These results suggest that the feeding responses of
      D. magna may be related to gut poisoning induced by the release of metals from
      algae under low pH conditions. In particular, both induction of metallothionein
      synthesis by Zn and competition between Zn and Cd ions for uptake at target sites
      on the gut wall may be involved in determining sublethal responses to mixtures of
      both metals.

PMID- 12204590
TI  - A comparison of the estrogenic potencies of estradiol, ethynylestradiol,
      diethylstilbestrol, nonylphenol and methoxychlor in vivo and in vitro.
AB  - Five natural, pharmaceutical, or xenobiotic chemicals [17beta-estradiol (E2),
      ethynylestradiol (EE2), diethystilbestrol (DES), methoxychlor (MXC), nonylphenol
      (NP)] were tested in two in vitro assays [yeast estrogen screen (YES), MCF-7
      breast tumor cell proliferation (E-Screen)], and compared with previously
      reported results from two in vivo male sheepshead minnow vitellogenin (VTG)
      production studies. The purpose of this investigation was to determine how
      accurately the two in vitro assays predicted responses observed in live animals.
      EC50 values for all five chemicals were approximately one order of magnitude less
      sensitive in the YES assay than in the MCF-7 assay. Based on the EC50 values, DES
      was 1.1 (YES) to 2.5 (MCF-7) times more potent in these receptor binding assays
      than was E2, while EE2 was slightly less potent than E2 in the YES assay (0.7)
      and nearly twice as potent (1.9) as E2 in the MCF-7 assay. EE2 and DES were of
      approximately equal potency in the 13-day sheepshead minnow VTG production
      bioassay. Both MXC and NP were 10(7) times less potent than E2 in the YES assay,
      MXC was 10(5) times less estrogenic than E2 in the MCF-7 assay, while both were
      approximately 100 times less potent than E2 in the live animal bioassay. The in
      vitro tests were substantially less sensitive (at least 1000 times) than the
      sheepshead minnow VTG assay for estimating estrogenic potency of the two
      xenobiotic chemicals, which suggests that in vitro-based, large-scale screening
      programs could potentially result in many false negative evaluations.

PMID- 12204591
TI  - Depuration and anatomical distribution of the amnesic shellfish poisoning (ASP)
      toxin domoic acid in the king scallop Pecten maximus.
AB  - The depuration kinetics of the domoic acid of four body fractions (digestive
      gland, adductor muscle, gonad+kidney and gills+mantle) of the scallop Pecten
      maximus was studied over 295 days. The scallops, which had acquired the toxins
      during a Pseudo-nitzschia australis episode that took place the week before the
      beginning of the experiment, were maintained in tanks with running seawater. All
      the body fractions, except the adductor muscle, decreased their domoic acid
      burden throughout the experiment. The amount of toxin in the muscle dropped
      sharply at the start of the experiment but increased again at the end, to levels
      that were higher than the initial ones. Several dynamic models of depuration
      kinetics, which included the depuration of each fraction (excluding the adductor
      muscle) and the transfers between them, were constructed, implemented and fitted
      to the data to obtain their parameters. The estimated depuration rates were very
      low, both considering and not considering the transfer of toxin between organs or
      the effect of weight loss. There were strong differences in the domoic acid
      burden of the body fractions studied but not between their depuration rates. No
      net transfer from the digestive gland, the tissue with highest domoic acid
      concentration, to the other fractions was found, as the inclusion of these
      processes in the models produced only a marginally better fit to the data. The
      depuration of domoic acid was slightly, but significantly, affected by biomass.
      Weight loss induced domoic acid loss, suggesting that part of the depuration may
      be produced by the direct loss of bivalve cells. The concentration or dilution
      effect, due to decreases or increases in biomass, documented for other species
      and toxins, has little importance in Pecten maximus.

PMID- 12204592
TI  - Inhibition of embryonic development and fertilization in broadcast spawning
      marine invertebrates by water soluble diatom extracts and the diatom toxin 2
      trans,4-trans decadienal.
AB  - Water soluble diatom extracts and the diatom aldehyde 2-trans,4-trans decadienal
      were assayed on the gametes and embryos of the broadcast spawning polychaetes
      Arenicola marina and Nereis virens and the echinoderms Asterias rubens and
      Psammechinus miliaris. Both crude cellular extracts and purified aldehyde were
      found to inhibit fertilization, embryogenesis and hatching success in a dose
      dependent manner. Intact diatom cells had no discernable effect on fertilization
      or development. Extracts of Skeletonema costatum were generally more effective
      than Nitzschia commutata in inhibiting development and fertilization. There was
      considerable interspecific variation in terms of toxin sensitivity. The
      polychaetes were more sensitive to the effects than the echinoderms. Within the
      polychaetes A. marina was the more tolerant in terms of developmental competence
      but N. virens had a higher fertilization rate. Echinoid embryos were more
      tolerant than asteroid embryos. This is the first study to present data on the
      inhibition of fertilization success by diatom extracts and aldehydes. Our
      observations are discussed in relation to temporal patterns in spawning and
      possible adaptive mechanisms to avoid diatom toxicity.

PMID- 12204593
TI  - Review of the background and application of triolein-containing semipermeable
      membrane devices in aquatic environmental study.
AB  - This paper briefly reviews research on passive in situ samplers for aquatic
      environments but focuses on the development and application of the triolein
      containing semipermeable membrane device in aquatic environmental monitoring.
      Special attention is paid to the calibration of the devices, quality control
      issues, and its potential uses in environmental assessments of aquatic
      contaminants. Also, the suitability of the technique for incorporation with
      selected bioassays is examined.

PMID- 12204595
TI  - Targeted drug delivery by thermally responsive polymers.
AB  - This review article summarizes recent results on the development of
      macromolecular carriers for thermal targeting of therapeutics to solid tumors.
      This approach employs thermally responsive polymers in conjunction with targeted
      heating of the tumor. The two thermally responsive polymers that are discussed in
      this article, poly(N-isopropylacrylamide-co-acrylamide) (poly(NIPAAm)) and an
      artificial elastin-like polypeptide (ELP), were designed to exhibit a soluble
      insoluble lower critical solution transition in response to increased temperature
      slightly above 37 degrees C. In vivo fluorescent videomicroscopy and radiolabel
      distribution studies of ELP delivery to human tumors implanted in nude mice
      demonstrated that hyperthermic targeting of the thermally responsive ELP for 1 h
      provides a approximately two-fold increase in tumor localization compared to the
      same polypeptide without hyperthermia. Similar results were also obtained for
      poly(NIPAAm) though the extent of accumulation was somewhat lesser than observed
      for the ELP. The endocytotic uptake of a thermally responsive ELP was also
      observed to be significantly enhanced by the thermally triggered phase transition
      of the polypeptide in cell culture for three different tumor cell lines.
      Preliminary cytotoxicity studies of an ELP-doxorubicin conjugate indicate that
      the ELP-doxorubicin conjugate has near equivalent cytotoxicity as free
      doxorubicin in a cell culture assay.

PMID- 12204596
TI  - Nanoparticles in cancer therapy and diagnosis.
AB  - Numerous investigations have shown that both tissue and cell distribution
      profiles of anticancer drugs can be controlled by their entrapment in submicronic
      colloidal systems (nanoparticles). The rationale behind this approach is to
      increase antitumor efficacy, while reducing systemic side-effects. This review
      provides an update of tumor targeting with conventional or long-circulating
      nanoparticles. The in vivo fate of these systems, after intravascular or tumoral
      administration, is discussed, as well as the mechanism involved in tumor
      regression. Nanoparticles are also of benefit for the selective delivery of
      oligonucleotides to tumor cells. Moreover, certain types of nanoparticles showed
      some interesting capacity to reverse MDR resistance, which is a major problem in
      chemotherapy. The first experiments, aiming to decorate nanoparticles with
      molecular ligand for 'active' targeting of cancerous cells, are also discussed
      here. The last part of this review focus on the application of nanoparticles in
      imaging for cancer diagnosis.

PMID- 12204597
TI  - Immunomodulating activities of soluble synthetic polymer-bound drugs.
AB  - The introduction of a synthetic material into the body always affects different
      body systems, including the defense system. Synthetic polymers are usually thymus
      independent antigens with only a limited ability to elicit antibody formation or
      to induce a cellular immune response against them. However, there are many other
      ways that they influence or can be used to influence the immune system of the
      host. Low-immunogenic water-soluble synthetic polymers sometimes exhibit
      significant immunomodulating activity, mainly concerning the
      activation/suppression of NK cells, LAK cells and macrophages. Some of them, such
      as poly(ethylene glycol) and poly[N-(2-hydroxypropyl)methacrylamide], can be used
      as effective protein carriers, as they are able to reduce the immunogenicity of
      conjugated proteins and/or to reduce non-specific uptake of liposome/nanoparticle
      entrapped drugs and other therapeutic agents. Recently, the development of
      vaccine delivery systems prepared from biodegradable and biocompatible water
      soluble synthetic polymers, microspheres, liposomes and/or nanoparticles has
      received considerable attention, as they can be tailored to meet the specific
      physical, chemical, and immunogenic requirements of a particular antigen and some
      of them can also act as adjuvants.

PMID- 12204598
TI  - Folate-mediated delivery of macromolecular anticancer therapeutic agents.
AB  - The receptor for folic acid constitutes a useful target for tumor-specific drug
      delivery, primarily because: (1) it is upregulated in many human cancers,
      including malignancies of the ovary, brain, kidney, breast, myeloid cells and
      lung, (2) access to the folate receptor in those normal tissues that express it
      can be severely limited due to its location on the apical (externally-facing)
      membrane of polarized epithelia, and (3) folate receptor density appears to
      increase as the stage/grade of the cancer worsens. Thus, cancers that are most
      difficult to treat by classical methods may be most easily targeted with folate
      linked therapeutics. To exploit these peculiarities of folate receptor
      expression, folic acid has been linked to both low molecular weight drugs and
      macromolecular complexes as a means of targeting the attached molecules to
      malignant cells. Conjugation of folic acid to macromolecules has been shown to
      enhance their delivery to folate receptor-expressing cancer cells in vitro in
      almost all situations tested. Folate-mediated macromolecular targeting in vivo
      has, however, yielded only mixed results, largely because of problems with
      macromolecule penetration of solid tumors. Nevertheless, prominent examples do
      exist where folate targeting has significantly improved the outcome of a
      macromolecule-based therapy, leading to complete cures of established tumors in
      many cases. This review presents a brief mechanistic background of folate
      targeted macromolecular therapeutics and then summarizes the successes and
      failures observed with each major application of the technology.

PMID- 12204599
TI  - Poly(L-glutamic acid)--anticancer drug conjugates.
AB  - Chemotherapy has had limited success in the treatment of cancer over the years,
      due, in part, to the untoward toxicity of the therapeutic agent to normal cells.
      The design of tailor-made polymer conjugates provides a synthetic approach that
      can overcome some of the problems. Several synthetic polymer-based anticancer
      drug conjugates have entered clinical studies. This report reviews the chemistry,
      physicochemical properties, and therapeutic applications in cancer therapy of
      polymeric chemotherapeutic agents based on poly(L-glutamic acid). Targeted
      delivery of anticancer agents using poly(L-glutamic acid) as the drug carrier is
      also discussed with emphasis on the design of innovative polymeric constructs.

PMID- 12204600
TI  - Prospects for cationic polymers in gene and oligonucleotide therapy against
      cancer.
AB  - Gene and antisense/ribozyme therapy possesses tremendous potential for the
      successful treatment of genetically based diseases, such as cancer. Several
      cancer gene therapy strategies have already been realized in vitro, as well as in
      vivo. A few have even reached the stage of clinical trials, most of them phase I,
      while some antisense strategies have advanced to phase II and III studies.
      Despite this progress, a major problem in exploiting the full potential of cancer
      gene therapy is the lack of a safe and efficient delivery system for nucleic
      acids. As viral vectors possess toxicity and immunogenicity, non-viral strategies
      are becoming more and more attractive. They demonstrate adequate safety profiles,
      but their rather low transfection efficiency remains a major drawback. This
      review will introduce the most important cationic polymers used as non-viral
      vectors for gene and oligonucleotide delivery and will summarize strategies for
      the targeting of these agents to cancer tissues. Since the low efficiency of this
      group of vectors can be attributed to specific systemic and subcellular
      obstacles, these hurdles, as well as strategies to circumvent them, will be
      discussed. Local delivery approaches of vector/DNA complexes will be summarized
      and an overview of the principles of anticancer gene and antisense/ribozyme
      therapy as well as an outline of ongoing clinical trials will be presented.

PMID- 12204601
TI  - Pluronic block copolymers for overcoming drug resistance in cancer.
AB  - Pluronic block copolymers have been used extensively in a variety of
      pharmaceutical formulations including delivery of low molecular mass drugs and
      polypeptides. This review describes novel applications of Pluronic block
      copolymers in the treatment of drug-resistant tumors. It has been discovered that
      Pluronic block copolymers interact with multidrug-resistant cancer (MDR) tumors
      resulting in drastic sensitization of these tumors with respect to various
      anticancer agents, particularly, anthracycline antibiotics. Furthermore, Pluronic
      affects several distinct drug resistance mechanisms including inhibition of drug
      efflux transporters, abolishing drug sequestration in acidic vesicles as well as
      inhibiting the glutathione/glutathione S-transferase detoxification system. All
      these mechanisms of drug resistance are energy-dependent and therefore ATP
      depletion induced by Pluronic block copolymers in MDR cells is considered as one
      potential reason for chemosensitization of these cells. Following validation
      using in vitro and in vivo models, a formulation containing doxorubicin and
      Pluronic mixture (L61 and F127), SP1049C, has been evaluated in phase I clinical
      trials. Further mechanistic studies and clinical evaluations of these systems are
      in progress.

PMID- 12204603
TI  - Exopolygalacturonate lyase from Thermotoga maritima: cloning, characterization
      and organic synthesis application.
AB  - A new exopolygalacturonate lyase (Pel) gene of the hyperthermophilic bacterium
      Thermotoga maritima was cloned and overexpressed in Escherichia coli cells. A 42
      kDa monomeric Pel was shown to undergo N-terminal processing by cleavage at a
      putative site between alanine and serine residues. The enzyme catalyzes
      selectively a beta-4,5 elimination at the third galacturonic unit from the
      reducing end of polygalacturonic acid by producing (4-deoxy-alpha-L-threo-hex-4
      enopyranosyluronic acid)-(1-->4)-(alpha-D-galactopyranosyluronic acid)-(1-->4)
      alpha-D-galactopyranuronic acid (3) with a 60% yield. The optimum activity of the
      enzyme was detected at pH 9.5 and T> or=95 degrees C. The highly thermostable
      enzyme constitutes a useful catalyst for a simplified synthesis of 4,5
      unsaturated trigalacturonic acid 3, a trisaccharide which is extremely difficult
      to obtain via chemical synthesis.

PMID- 12204604
TI  - Structural analysis of the lipopolysaccharide from Neisseria meningitidis strain
      BZ157 galE: localisation of two phosphoethanolamine residues in the inner core
      oligosaccharide.
AB  - The structure of the phase-variable lipopolysaccharide (LPS) from the group B
      Neisseria meningitidis strain BZ157 galE was elucidated. The structural basis for
      the LPS's variation in reactivity with a monoclonal antibody (MAb) B5 that has
      specificity for the presence of phosphoethanolamine (PEtn) at the 3-position of
      the distal heptose residue (HepII) was established. The structure of the O
      deacylated LPS was deduced by a combination of monosaccharide analyses, nuclear
      magnetic resonance (NMR) spectroscopy and mass spectrometry. These analyses
      revealed the presence of a novel inner core oligosaccharide (OS) structure in the
      MAb B5 reactive (B5+) LPS that contained two PEtn residues simultaneously
      substituting the 3- and 6-positions of the HepII residue. The determination of
      this structure has identified a further degree of variability within the inner
      core OS of meningococcal LPS that could contribute to the interaction of
      meningococcal strains with their host.

PMID- 12204605
TI  - Determination of structural peculiarities of dexran, pullulan and gamma
      irradiated pullulan by Fourier-transform IR spectroscopy.
AB  - Deconvoluted IR-absorbance spectra of dextran, pullulan and gamma-irradiated
      pullulan were analyzed in order to find the most specific spectral peculiarities
      that allow one to obtain information about the structure and conformation of
      these macromolecules in solvents that exhibit different influences on the system
      of intra- and intermolecular interactions. The changes in intensity and width of
      the IR bands at about 1040, 1020 and, in the case of pullulan, also at 996 cm(
      1), were related to changes in conformation and short-range interactions of the
      polysaccharides. Furthermore, certain bands within the 1200-900 cm(-1) region
      were considered as a characteristic for the type of glycosidic linkage. The
      results of the FTIR spectroscopy study allowed one to suggest a predominant
      cleavage of the alpha-(1-->4) linkages upon the radiation-chemical destruction of
      pullulan.

PMID- 12204606
TI  - The properties of enzyme-hydrolyzed cellulose in aqueous sodium hydroxide.
AB  - Pure natural cellulose (softwood pulp) modified with cellulase is allowed to
      react with sodium hydroxide in a muller, and changes in structure and properties
      are investigated by FTIR and DSC. The reactivity of cellulose for some dissolving
      and derivatization processes is shown to be improved by an enzymatic hydrolysis
      and admixture with sodium hydroxide. The modified cellulose dissolved at 9% (wt)
      sodium hydroxide at -10 degrees C at 6% pulp consistency, while the DP of
      cellulose is >350.

PMID- 12204607
TI  - LaPSvS1, a (1-->3)-beta-galactan sulfate and its effect on angiogenesis in vivo
      and in vitro.
AB  - LaPSvS1, a highly sulfated branched (1-->3)-beta-galactan was prepared from the
      arabino-galactan from Larix decidua Miller by partial hydrolysis and subsequent
      sulfation with SO(3)-pyridine in DMF. The molecular weight was analyzed by GPC
      and the sulfate content was determined by ion chromatography. LaPSvS1 exhibited
      good antiangiogenic and antiinflammatory effects in two different modifications
      of the known CAM-assay. In vitro results obtained in the FGF-2-trypsin-assay and
      in fluorospectrometric experiments revealed that LaPSvS1 interacts with the
      fibroblast growth factor 2 system. This interaction is correlated with the in
      vivo effect of LaPSvS1 on FGF-2 induced angiogenesis.

PMID- 12204608
TI  - Structural features of non-granular spherulitic maize starch.
AB  - Complementary analyses of the internal structure of spherulites crystallized from
      high-amylose maize starch were obtained using light, electron and atomic force
      microscopy. Radially oriented crystalline lamellae were observed in transmission
      and scanning electron microscopy, as well as AFM. Internal structures consistent
      with the central hilum region of starch granules were observed. Spherulites were
      composed largely of linear or lightly branched starch polymers. Degradation of
      amylopectin at gelatinization temperatures of 180 degrees C was evident, but
      iodine binding suggested a high molecular weight (>100 DP) for the spherulitic
      polymers.

PMID- 12204609
TI  - Synthesis and characterization of 4,6-O-butylidene-N-(2-hydroxybenzylidene)-beta
      D-glucopyranosylamine: crystal structures of 4,6-O-butylidene-alpha-D
      glucopyranose, 4,6-O-butylidene-beta-D-glucopyranosylamine and 4,6-O-butylidene-N
      (2-hydroxybenzylidene)-beta-D-glucopyranosylamine.
AB  - 4,6-O-Butylidene-N-(2-hydroxybenzylidene)-beta-D-glucopyranosylamine was
      synthesized and characterized using analytical, spectral and single-crystal X-ray
      diffraction methods. 1H and 13C NMR studies showed the presence of the beta
      anomer, which has also been confirmed by the crystal structure. The molecular
      structure of this compound showed the presence of the tridentate ONO ligation
      core. Both precursors, 4,6-O-butylidene-alpha-D-glucopyranose and 4,6-O
      butylidene-beta-D-glucopyranosylamine were characterized using single crystal X
      ray diffraction. The alpha-anomeric nature of the former and beta-anomeric nature
      of the latter were proposed based on 1H NMR studies and were confirmed by
      determining the crystal structures. In addition, the crystal structure of 4,6-O
      butylidene-beta-D-glucopyranosylamine revealed the C-1-N-glycosylation. In all
      the three molecules, the saccharide unit exhibits a 4C(1) chair conformation. In
      the lattice, the molecules are connected by hydrogen-bond interactions. The
      conformation of 4,6-O-butylidene-N-(2-hydroxybenzylidene)-beta-D
      glucopyranosylamine is stabilized via an O-H...N intramolecular interaction, and
      each molecule in the lattice interacts with three neighboring molecules through
      hydrogen bonds of the type O-H...O and C-H...O.

PMID- 12204610
TI  - Sugar interaction with metal ions. The coordination behavior of neutral
      galactitol to Ca(II) and lanthanide ions.
AB  - The crystal structures of CaCl(2).galactitol.4 H(2)O and 2EuCl(3).galactitol.14
      H(2)O were determined to compare the coordination behavior of Ca and lanthanide
      ions. The crystal system of the Ca-galactitol complex, CaCl(2).C(6)H(14)O(6).4
      H(2)O, is monoclinic, Cc space group. Each Ca ion is coordinated to eight oxygen
      atoms, four from two galactitol molecules and four from water molecules.
      Galactitol provides O-2, -3 to coordinate to one Ca(2+), and O-4, -5 with another
      Ca(2+), to form a chain structure. The crystal system of the Eu-galactitol
      complex, 2EuCl(3).C(6)H(14)O(6).14 H(2)O, is triclinic, P1; space group. Each Eu
      ion is coordinated to nine oxygen atoms, three from an alditol molecule and six
      from water molecules. Each galactitol provides O-1, -2, -3 to coordinate with one
      Eu(3+) and O-4, -5, -6 with another Eu(3+). The other water molecules are
      hydrogen-bonded in the structure. The similar IR spectra of Pr-, Nd-, Sm-, Eu-,
      Dy-, and Er-galactitol complexes show that those lanthanide ions have the same
      coordination mode to neutral galactitol. The Raman spectra also confirm the
      formation of metal ion-carbohydrate complexes.

PMID- 12204611
TI  - Side products of glycosidation with selected 2-acetamido-2-deoxy-D
      glucopyranosides.
AB  - Allyl 2-acetamido-4,6-O-benzylidene-2-deoxy-3-O-formyl-alpha-D-glucopyranoside, N
      acetyl-2,3,4-tri-O-acetyl-L-fucopyranosylamine and products of O-acetyl group
      migration were found as side products during glycosidation of selected 2
      acetamido-2-deoxy-D-glucopyranosides.

PMID- 12204612
TI  - Simultaneous regioselective protection of phenyl 1-thioglucosides at the C-3 and
      C-6 or at the C-2 and C-6 hydroxy groups.
AB  - Simultaneous regioselective 3,6- or 2,6-selective protection of 1-thio-beta- or
      alpha-D-glucopyranosides is described. The C-3 and C-6 hydroxy groups of the beta
      thioglucoside were selectively protected with triisopropylsilyl or tert
      butyldiphenylsilyl trifluoromethanesulfonate. The C-2 and C-6 hydroxy groups of
      the alpha-thioglucoside were selectively protected with tert-butyldiphenylsilyl
      trifluoromethanesulfonate.

PMID- 12204613
TI  - Fungal cell wall galactomannan isolated from Apodus deciduus.
AB  - The alkali-extractable water-soluble polysaccharide (F1SS) isolated from the cell
      wall of Apodus deciduus has been studied by methylation analysis and NMR
      spectroscopy, and its structure established as:where n approximately 130+/-10.

PMID- 12204614
TI  - Structural studies on C-2 substitution in a new set of synthetic aminodideoxy
      sugars: the steric bulk at C-2 influences the puckering of the pyranose ring.
AB  - Synthesis and single-crystal X-ray structural analyses of selected aminodideoxy
      sugars with different group substitutions at the C-2 position were carried out.
      Product formation and X-ray crystallographic determination of the products from C
      2 substitution in both alpha and beta anomers were studied. The observed
      variation in pyranose ring conformations in product compounds is explained in
      terms of C-2 substitution.

PMID- 12204616
TI  - Synthesis of building blocks of human milk oligosaccharides. Fucosylated
      derivatives of the lacto- and neolacto-series.
AB  - The synthesis of protected fucosylated derivatives of a Galbeta(1-->3)GlcNAc and
      of lactosamine Galbeta(1-->4)GlcNAc building blocks contained in human milk
      oligosaccharides is described. Both chemical and enzymatic methods have been
      exploited for selective protection of the disaccharide. Fucosylation of the
      appropriate derivatives allowed an easy and relatively short access to different
      products from common precursors.

PMID- 12204617
TI  - Synthesis of ceramidated GLA-60 derivatives.
AB  - Ceramidated GLA-60 derivatives 11 and 11' were synthesized from 1 via
      glycosidation of ceramide derivative 12 as a glycosyl acceptor with GLA-60
      derivative 5 as a glycosyl donor, and successive conversion. Compound 11' showed
      only weak LPS-antagonistic activity without showing any LPS-agonistic activity.

PMID- 12204618
TI  - Synthesis of 4-cyano and 4-nitrophenyl 1,6-dithio-D-manno-, L-ido- and D
      glucoseptanosides possessing antithrombotic activity.
AB  - 1,6-Anhydro-3,4-O-isopropylidene-1-thio-D-mannitol was converted into its
      sulfoxide which after hydrolysis, acetylation and subsequent Pummerer
      rearrangement gave the penta-O-acetyl-1-thio-D-mannoseptanose anomers in
      excellent yield. This anomeric mixture was used as donor for the glycosylation of
      4-nitro- and 4-cyanobenzenethiol in the presence of boron trifluoride etherate
      and trimethylsilyl triflate, respectively, to yield the corresponding
      thioseptanosides in high yield. The same strategy was applied for the synthesis
      of the corresponding L-idothioseptanosides using 1,6-anhydro-3,4-O-isopropylidene
      1-thio-L-iditol as starting material. The penta-O-acetyl-D-glucothioseptanose
      donors could not be synthesised the same way, as the Pummerer reaction of the
      corresponding tetra-O-acetyl-1,6-thioanhydro-1-thio-D-glucitol sulfoxides led to
      an inseparable mixture of the corresponding L-gulo- and D-glucothioseptanose
      anomers. Therefore, D-glucose diethyl dithioacetal was converted via its 2,3,4,5
      tetra-O-acetyl-6-S-acetyl derivative into an anomeric mixture of its 6-thio
      septanose and -furanose peracetates which could be separated by column
      chromatography. Condensation of the 6-thio-glucoseptanose peracetates with 4
      cyano- and 4-nitrobenezenethiol in the presence of boron trifluoride etherate
      afforded anomeric mixtures of the corresponding thioseptanosides. The D-manno-, L
      ido- and D-glucothioseptanosides obtained after Zemplen deacetylation of these
      mixtures were tested for their oral antithrombotic activity.

PMID- 12204619
TI  - Synthesis of a mannose heptasaccharide of the pathogenic yeast, Candida glabrata
      IFO 0622 strain.
AB  - An effective synthesis of the mannose heptasaccharide existing in the pathogenic
      yeast, Candida glabrata IFO 0622 strain was achieved via TMSOTf-promoted
      condensation of a tetrasaccharide donor 13 with a trisaccharide acceptor 16,
      followed by deprotection. The tetrasaccharide 13 was constructed by coupling of
      2,3,4,6-tetra-O-benzoyl-alpha-D-mannopyranosyl-(1-->3)-2,4,6-tri-O-acetyl-alpha-D
      mannopyranosyl trichloroacetimidate (7) with allyl 3,4,6-tri-O-benzoyl-alpha-D
      mannopyranosyl-(1-->2)-3,4,6-tri-O-benzoyl-alpha-D-mannopyranoside (10), followed
      by deallylation and trichloroacetimadation. The trisaccharide 16 was obtained by
      coupling of 6-O-acetyl-2,3,4-tri-O-benzoyl-alpha-D-mannopyranosyl
      trichloroacetimidate with 10, and subsequent 6-O-deacetylation. The disaccharide
      7 was prepared through coupling of perbenzoylated mannosyl trichloroacetimidate
      with 4,6-O-benzylidene-1,2-O-ethylidene-beta-D-mannopyranose, then simultaneous
      debenzylidenation and deethylidenation, and subsequent acetylation, selective 1-O
      deacetylation, and trichloroacetimidation. The disaccharide 10 was obtained by
      self-condensation of 3,4,6-tri-O-benzoyl-1,2-O-allyloxyethylidene-beta-D
      mannopyranose, followed by selective 2-O-deacetylation.

PMID- 12204620
TI  - A practical synthesis of beta-D-GlcA-(1-->3)-beta-D-Gal-(1-->3)-beta-D-Gal-(1-
      >4)-D-Xyl, a part of the common linkage region of a glycosaminoglycan.
AB  - A practical synthesis of beta-D-GlcA-(1-->3)-beta-D-Gal-(1-->3)-beta-D-Gal-(1-
      >4)-beta-D-Xyl-(1-->OMe) was achieved by coupling of methyl 2,3,4-tri-O-acetyl
      alpha-D-glucopyranosyluronate trichloroacetimidate with a trisaccharide acceptor.
      The trisaccharide acceptor was obtained by condensation of 3-O-allyl-2,4,6-tri-O
      benzoyl-beta-D-galactopyranosyl-(1-->3)-2,4,6-tri-O-benzoyl-alpha-D
      galactopyranosyl trichloroacetimidate with methyl 2,3-di-O-benzoyl-beta-D
      xylopyranoside, followed by deallylation. The beta-(1-->3)-linked disaccharide
      was prepared readily with p-methoxyphenyl 3-O-allyl-2,4,6-tri-O-benzoyl-beta-D
      galactopyranoside as the key synthon. The alpha-(1-->3)-linkage was formed in
      considerable amount with galactose mono- and disaccharide trichloroacetimidate
      donors with C-2 neighboring group participation.

PMID- 12204621
TI  - Structure of the O-polysaccharide of Aeromonas hydrophila O:34; a case of random
      O-acetylation of 6-deoxy-L-talose.
AB  - The O-polysaccharide of Aeromonas hydrophila O:34 was obtained by mild-acid
      degradation of the lipopolysaccharide and studied by chemical methods and NMR
      spectroscopy before and after O-deacetylation. The polysaccharide was found to
      contain D-Man, D-GalNAc and 6-deoxy-L-talose (L-6dTal), and the following
      structure of the tetrasaccharide repeating unit was established [carbohydrate
      structure see text] where 6dTal(I) is O-acetylated stoichiometrically at position
      2 and 6dTal(II) carries no, one or two O-acetyl groups at any positions.

PMID- 12204622
TI  - The self-association of the drug acemetacin and its interactions and
      stabilization with beta-cyclodextrin in aqueous solution as inferred from NMR
      spectroscopy and HPLC studies.
AB  - Strongly concentration dependent, (1)H NMR chemical shifts of the non-steroidal
      anti-inflammatory drug acemetacin sodium salt (sodium [[1-(4-chlorobenzoyl)-5
      methoxy-2-methylindol-3-yl]acetoxy]acetate), were observed in aqueous solution.
      Self-titration and nOe experiments, point to a self-association model where
      stacking takes place via the indole portion of the drug. In addition,
      conformational isomerism (atropisomerism) of the anti to syn form was confirmed.
      Further increase of the concentration eventually led to stable chemical shifts
      and nearly simultaneous appearance of microcrystals. In the presence of betaCD,
      1:1 inclusion complexation occurred through the p-chlorobenzoyl part of the drug,
      whereas with excess betaCD the indole part seemed to participate to a minor
      degree. The anti isomer is suggested to be involved in the inclusion process. In
      addition, aggregation of acemetacin was also evident, as competing with the
      conformational and inclusion equilibria. The present case demonstrates that many
      competitive processes are simultaneously active in a seemingly simple system. The
      measurements were strongly dependent upon the pH and use of buffered solutions
      was mandatory. Finally, for the quantitative analysis of acemetacin in the
      presence of betaCD, a special HPLC method was developed. The stability of the
      drug, studied by the identification of the degradation products and the pseudo
      first order rate of hydrolysis, was found to be unaffected by the presence of
      betaCD.

PMID- 12204623
TI  - Heterocyclization of 3-deoxy-D-erythro-hexos-2-ulose-1,2-bis(thiosemicarbazone).
      Crystal structure of the major diastereomer.
AB  - Both thiosemicarbazone groups of the derivative 1 of 3-deoxy-D-erythro-hexos-2
      ulose underwent, on acetylation, a heterocyclization process to give (5R,5'R)
      2,2'-diacetamido-4,4'-di-N-acetyl-5'-(1-deoxy-2,3,4-tri-O-acetyl-D-erythritol-1
      yl)-5,5'-bis(1,3,4-thiadiazoline) (2) as a major product. The X-ray diffraction
      data of a single crystal of 2 indicated the R,R configuration for the
      stereocenters of the thiadiazoline rings (C-5 and C-5'). In the solid state, 2
      adopts a sickle conformation (by clockwise rotation of the C-2-C-3 axis of the
      sugar chain) which has a S//O 1,3-parallel interaction. In solution, as
      determined by (1)H NMR spectroscopy which included NOE experiments, a similar
      sickle conformation was observed. From the reaction mixture of acetylation of 1
      was isolated the bis(thiadiazoline) 3 as a by-product. The configuration of the C
      5 and C-5' stereocenters of 3 were respectively assigned as S,R by comparison of
      the physical and spectroscopic data of this compound with those of 2.

PMID- 12204624
TI  - Interaction between carbohydrate residues of alpha(1)-acid glycoprotein
      (orosomucoid) and progesterone. A fluorescence study.
AB  - Interaction between progesterone and the carbohydrate residues of alpha(1)-acid
      glycoprotein was followed by fluorescence studies using calcofluor white. The
      fluorophore interacts with polysaccharides and is commonly used in clinical
      studies. Binding of progesterone to the protein induces a decrease in the
      fluorescence intensity of calcofluor white, accompanied by a shift to the short
      wavelengths of its emission maximum. The dissociation constant of the complex was
      found equal to 8.62 microM. Interaction between progesterone and free calcofluor
      in solution induces a low decrease in the fluorescence intensity of the
      fluorophore without any shift of the emission maximum. These results show that in
      alpha(1)-acid glycoprotein, the binding site of progesterone is very close to the
      carbohydrate residues. Fluorescence intensity quenching of free calcofluor in
      solution with cesium ion gives a bimolecular diffusion constant (k(q)) of 2.23 x
      10(9) M(-1) s(-1). This value decreases to 0.19 x 10(9) M(-1) s(-1) when
      calcofluor white is bound to alpha(1)-acid glycoprotein. Binding of progesterone
      does not modify the value of k(q) of the cesium. Previous studies have shown that
      the terminal sialic acid residue is mobile, while the other glycannes are rigid
      [Albani, J. R.; Sillen, A.; Coddeville, B.; Plancke, Y. D.; Engelborghs, Y.
      Carbohydr. Res. 1999, 322, 87-94]. Red-edge excitation spectra and Perrin plot
      experiments performed on sialylated and asialylated alpha(1)-acid glycoprotein
      show that binding of progesterone to alpha(1)-acid glycoprotein does not modify
      the local dynamics of the carbohydrate residues of the protein.

PMID- 12204625
TI  - An improved synthesis of 5-thio-D-ribose from D-ribono-1,4-lactone.
AB  - 5-Thio-D-ribopyranose was synthesized from D-ribono-1,4-lactone (1) by two
      approaches: (i) 5-bromo-5-deoxy-D-ribono-1,4-lactone (2) was successively
      transformed into 5-bromo-5-deoxy, 5-S-acetyl-5-thio or 5-thiocyanato-D
      ribofuranose derivatives; appropriate treatment then lead to 5-thio-D
      ribopyranose (7) in 46-48% overall yield and; (ii) 2 was transformed into the 5-S
      acetyl-5-thio-D-ribono-1,4-lactone derivative (11). Reduction and deprotection of
      11 afforded 5-thio-D-ribopyranose (7) in 57% overall yield.

PMID- 12204626
TI  - Structural characterization of a water-soluble beta-D-glucan from fruiting bodies
      of Agaricus blazei Murr.
AB  - A beta-D-glucan, Ab2-2N, was isolated from the hot-water extract of fruiting
      bodies of Agaricus blazei Murr by ethanol precipitation, anion-exchange and gel
      permeation chromatography. Its structure was investigated by composition
      analysis, methylation analysis, Smith degradation, mild hydrolysis, and NMR
      spectroscopy. It contains a (1-->6)-linked beta-D-glucopyranosyl backbone, with
      one side chain consisting of terminal and 3-substituted beta-D-glucopyranosyl
      residues attached at O-3 for every three backbone residues.

PMID- 12204627
TI  - The pharmacokinetic-pharmacodynamic approach to a rational dosage regimen for
      antibiotics.
AB  - Pharmacokinetic-pharmacodynamic (PK/PD) surrogate indices (AUIC, AUC/MIC,
      C(max)/MIC, T>MIC) for measuring antibiotic efficacy are presented and reviewed.
      As clinical trials are not sufficiently sensitive to establish a dosage regimen
      which guarantees total bacteriological cure (Pollyanna phenomenon), PK/PD indexes
      have been proposed from in vitro, ex vivo, and in vivo infection models and
      subsequently validated in retrospective or prospective human clinical trials. The
      target value for time-dependent antibiotics (beta-lactams, macrolides) is a time
      above the MIC (T>MIC) of 50-80% of the dosage interval, while for concentration
      dependent antibiotics (quinolones and aminoglycosides), the area under the
      inhibitory curve (AUIC, or more simply AUC/MIC of about 125h) is the best
      surrogate indicator of activity. Using the latter drugs, high concentrations
      achieved early during therapy are desirable to prevent the development of
      resistance. A C(max)/MIC ratio greater than 10-12 seems to be an appropriate
      target for aminoglycosides.

PMID- 12204628
TI  - Cortisol responses to dehorning of calves given a 5-h local anaesthetic regimen
      plus phenylbutazone, ketoprofen, or adrenocorticotropic hormone prior to
      dehorning.
AB  - The purpose of this work was to assess whether the non-steroidal anti
      inflammatory drugs (NSAIDs) phenylbutazone and ketoprofen, and an
      adrenocorticotropic hormone (ACTH) induced cortisol surge, reduce the cortisol
      response which occurs when the local anaesthetic wears off in calves following
      dehorning. There were four control groups and one dehorned group; also four
      groups were given local anaesthetic lasting 5h and were dehorned without or with
      phenylbutazone, ketoprofen or an ACTH injection, one group was injected with ACTH
      twice (at 0 and 6h) and another received ACTH and 6h later was dehorned. Blood
      samples were taken before and after dehorning and plasma cortisol concentrations
      were determined by radio-immunoassay. Dehorning increased the mean plasma
      cortisol concentrations [max 137 (11)nmoll(-1)] above control values [38
      (5)nmoll(-1)] for about 7h, whereas local anaesthesia maintained concentrations
      at control values until about 5h after dehorning, and then they became elevated
      until about 10h. The maximum rise in mean concentration which occurred when the
      local anaesthetic wore off [128 (32)nmoll(-1)] was not affected when
      phenylbutazone was given before dehorning [141 (28)nmoll(-1)], but was reduced
      significantly when ketoprofen [65 (17)nmoll(-1)] or ACTH [61 (19)nmoll(-1)] were
      injected before or at the time of dehorning, respectively. Marked cortisol
      responses to ACTH injected at 0 and 6h were similar, but the early part of the
      cortisol response to dehorning 6h after an ACTH injection was reduced. It is
      suggested that the delayed cortisol response, which began 5h after dehorning,
      arose both from ketoprofen-sensitive and cortisol-sensitive sensory input as well
      as from other factors. Phenylbutazone did not affect the sensory input from the
      amputation wounds in the present calves.

PMID- 12204629
TI  - Disposition kinetics of enrofloxacin (Baytril 5%) in sheep and goats following
      intravenous and intramuscular injection using a microbiological assay.
AB  - The pharmacokinetics of enrofloxacin were determined in Desert sheep and Nubian
      goats after intravenous and intramuscular administration of Baytril at the dose
      of 5mgkg(-1) bodyweight. A two compartment open model best represented the
      intravenous plasma concentration versus time data in both species. Comparisons
      between the means of the pharmacokinetic parameters obtained after intravenous
      administration of enrofloxacin (Baytril) revealed a significantly smaller
      distribution rate constant (lambda(1)) and consequently a shorter half-life time
      of distribution in sheep (P<0.05). A larger volume of the central compartment
      (Vc) was observed in goats (P<0.05). Similar values were obtained for sheep and
      goats for the remaining parameters. Plasma concentrations versus time data of
      enrofloxacin after 5mgkg(-1) intramuscular administration of Baytril in sheep and
      goats were adequately described by one-compartment open model with first order
      absorption and elimination. There were no significant differences between sheep
      and goats in any of the estimated pharmacokinetic parameters. The results
      indicate that the pharmacokinetics of enrofloxacin did not differ significantly
      between sheep and goats; similar intravenous and intramuscular dose rates of
      enrofloxacin should therefore be applicable to both species. Owing to the high
      variations in MIC (minimal inhibitory concentration) of sensitive veterinary
      pathogens, it is recommended that enrofloxacin dosage regimens be calculated
      according to the sensitivity of the individual pathogen, site of infection and
      clinical response, than by following a preset dosage regimen.

PMID- 12204630
TI  - Distribution of the hyaluronate lyase encoding gene hylB and the insertion
      element IS1548 in streptococci of serological group B isolated from animals and
      humans.
AB  - The present study was performed to investigate streptococci of serological group
      B obtained from various sources and group B streptococcal reference strains for
      serotype, hyaluronate lyase enzyme activity, the occurrence of the hylB gene and
      the insertion sequence IS1548. All group B streptococci were identified by
      cultural, biochemical, and serological properties and by polymerase chain
      reaction amplification of species-specific parts of the 16S-23S rDNA intergenic
      spacer region, the 16S rRNA gene and the CAMP-factor (cfb) gene. Of the 73 group
      B streptococci investigated, 59 strains displayed hyaluronate lyase enzyme
      activity. All hyaluronate-lyase-positive strains and three phenotypically
      hyaluronate-lyase-negative strains had a hylB gene with an amplicon size of
      3.3kb. Eleven of the 14 phenotypically hyaluronate-lyase-negative strains
      generated a hylB gene PCR product with a size of 4.6kb, and 10 of these strains
      displayed a IS1548 amplicon with a size of 0.98kb. The hyaluronate-lyase-negative
      isolates were mainly observed among group B streptococci of serotype III/Rib. All
      strains harbouring IS1548 had an additional copy of IS1548 located downstream of
      the C5a peptidase (scpB) gene.

PMID- 12204631
TI  - Pharmacokinetics of florfenicol in healthy and Escherichia coli-infected broiler
      chickens.
AB  - The pharmacokinetics of florfenicol were studied in both healthy (n=9) and
      Escherichia coli-infected (n=27) broiler chickens following intravenous (i.v.),
      intramuscular (i.m.) and oral administration at a single dose of 30 mg/kgbw.
      Infection was induced artificially in broiler chickens (35 d) by an
      intraperitoneal injection with 1.3 x 10(9) colony-forming units of E. coli. After
      i.v. administration in healthy and infected broiler chickens, the disposition
      kinetics of florfenicol were described by a bi-exponential equation. In diseased
      broiler chickens, a decrease in the elimination half-life and the apparent volume
      of distribution were found. The pharmacokinetic parameters such as total body
      clearance and the areas under curves of plasma concentrations were comparable in
      healthy and E. coli infected chickens. Following i.m. and oral administration in
      infected chickens, the plasma concentration-time data for florfenicol were found
      to fit a single-compartment open model. The elimination half-lives (t(1/2 el)) of
      florfenicol were 129(13) and 104(15)min, the systemic bioavailability 87% and 71%
      after i.m. and oral administration.

PMID- 12204632
TI  - Disposition kinetics of tylosin administered intravenously and intramuscularly to
      pigs.
AB  - The distribution of tylosin was studied using a crossover design, in six pigs
      following i.v. and i.m. administration of 10 mgkg(-1) b.w. Plasma samples were
      analysed by HPLC and UV absorbance detection. After i.v. administration,
      t(1/2beta) was 271.3 min, V(d) 14.6 Lkg(-1), V(ss) 9.7 Lkg(-1) and CL 26.8 mLmin(
      1)kg(-1). After i.m. administration, a C(max) of 1 microgmL(-1) was reached at 90
      min. Mean absorption time was 1988.7 min and bioavailability was 95%.

PMID- 12204633
TI  - The efficacy of bacille Calmette-Guerin vaccine in wild brushtail possums
      (Trichosurus vulpecula).
AB  - A population of wild brushtail possums (Trichosurus vulpecula) in which bovine
      tuberculosis was endemic was vaccinated with live bacille Calmette-Guerin (BCG)
      to determine the efficacy of vaccination. The population on the 56 hectare site
      was monitored bimonthly over 2 years using a capture-release regime. During the
      study tuberculosis was diagnosed by clinical and post mortem examination. Possums
      were vaccinated with BCG by both intranasal aerosol and conjunctival
      instillation. Possums were revaccinated on average every 5 months. Over the 2
      years, 300 possums were recruited to the study with 149 being allocated to the
      vaccination group. There were significantly fewer cases of tuberculosis in the
      vaccinated (4 cases) than in the unvaccinated group (13 cases; P=0.023). The
      vaccine efficacy was 69%. An attempt was made to increase the incidence of
      disease by releasing onto the site possums that had been experimentally infected
      with a strain of M. bovis unknown in the area. However, this did not result in
      any additional cases. BCG vaccine was shown to have a level of efficacy which
      could be of assistance in controlling tuberculosis in wild possum populations.
      The future use of vaccination for the control of tuberculosis in wild possum
      populations is discussed.

PMID- 12204634
TI  - Fatty acid composition of serum lipids in atopic and healthy dogs.
AB  - Fatty acids are increasingly used in the treatment of canine atopic dermatitis
      and their beneficial effects are documented in several prospective, controlled
      studies. Results from recent studies have indicated that atopic dogs have
      disordered fat metabolism, due to decreased desaturase activity. To further
      clarify these possible abnormalities, we examined serum fatty acid patterns in
      dogs with atopic dermatitis and normal controls. Atopic dermatitis was diagnosed
      according to the diagnostic criteria proposed by Willemse, after elimination of
      other possible causes of pruritic dermatitis. Both the relative and the absolute
      amounts of fatty acids in sera were determined by gas chromatography. Differences
      in the serum fatty acid pattern indicating a reduction in desaturase activity
      were not detected in atopic dogs when compared with controls.

PMID- 12204635
TI  - Cloning of canine 21-hydroxylase gene and its polymorphic analysis as a candidate
      gene for congenital adrenal hyperplasia-like syndrome in Pomeranians.
AB  - A Strong breed predisposition to canine congenital adrenal hyperplasia-like
      syndrome (CAH-LS) exists and implies there is an hereditary cause. Pomeranians,
      one of the most predisposed breeds, have been reported to have partial adrenal
      dysfunction that could be associated with the pathogenesis of CAH-LS. In this
      study, the full-length complementary DNA (cDNA) of canine 21-OH, whose mutations
      are most likely responsible for the adrenal dysfunction in Pomeranians, was
      initially obtained from adrenal gland RNA by reverse transcription-polymerase
      chain reaction (RT-PCR), and its nucleotide sequence was determined. Genomic DNA
      samples from 16 Pomeranians and 30 control dogs, of seven different breeds, were
      tested for 21-OH gene polymorphisms by direct sequencing. No mutations affecting
      the primary structure and the transcriptional level of the 21-OH enzyme were
      found in Pomeranians. Our results indicate that the adrenal dysfunction in
      Pomeranians is not due to mutations of the 21-OH gene. This contrasts with the
      human form of CAH where 21-OH gene mutations are the major cause of the disease.

PMID- 12204636
TI  - Commercial variants of the prothrombin time test as a screening test of acquired
      coagulation factor II, VII, and X deficiencies in dogs.
AB  - The aim of this study was to acquire the single factor sensitivity of three
      commercial variants of the prothrombin time test (PT(Va1)-Thrombotest, PT(Va2)
      Normotest, PT(Va3)-Hepato Quick) for canine plasma. For this purpose, 38 samples
      from animals with coumarin intoxication followed by vitamin K(1) treatment who
      had a reduced activity of the coagulation factors II, VII, and/or X (experiment
      1) as well as 25 plasma samples from animals with moderately reduced activity of
      the coagulation factors II, V, VII, and/or X caused by a hepatogenic synthesis
      disorder or disseminated intravascular coagulation (experiment 2), were examined.
      Measurements for all tests were performed according to the instructions of the
      manufacturer and also with higher plasma dilution. Furthermore, control
      measurements were performed with the conventional prothrombin time test (standard
      test; PT(ST)). The prothrombin time measured with the PT(Va3), which was
      prolonged in all samples from experiments 1 and 2, especially reflected with high
      sensitivity the reduced activity of the coagulation factors. The measurements
      with PT(Va2) and PT(Va1) showed only an insignificantly lower sensitivity (> or
      =0.88) with a maximum of 1 (experiment 1) and 3 (experiment 2) false negative
      test results, respectively. Compared to the already high sensitivity, a higher
      dilution of the sample material did not lead to a significantly higher
      sensitivity (P>0.05) for any of the tested commercial variants of the prothrombin
      time assay. While there was no significant difference (P>0.05) between the number
      of false negative test results in the variants of the prothrombin time assay, in
      both experiments a significantly higher number of false negative test results was
      found for the PT(ST) (P<0.001). The results show that, in contrast to the PT(ST),
      all three tested commercial prothrombin time variants are suitable for the
      detection of deficiencies of coagulation factors II, VII, and X in canine plasma.

PMID- 12204637
TI  - Effects of a P2Y(12) receptor antagonist on the response of equine platelets to
      ADP. Comparison with human platelets.
AB  - Horses show susceptibility to platelet-related disorders. Equine platelets differ
      from human platelets in some of their responses, so information available about
      human platelets must be validated in the horse. Aggregation of platelets by ADP
      involves both P2Y(1) and P2Y(12) receptors on the platelet surface. We have
      compared the effect of the P2Y(12) antagonist, AR-C67085, on equine and human
      platelets in vitro using turbidimetric aggregometry to measure the rate and final
      extent of aggregation. Aggregation profiles, concentration-response curves and
      pA(2) values show that the rate of aggregation of equine platelets is much more
      susceptible to inhibition by AR-C67085 than that of human platelets. This species
      difference may reflect differences in the relative numbers of P2Y(1) and P2Y(12)
      receptors, or in intracellular signalling pathways, but will need to be
      considered by equine clinicians before using P2Y(12) antagonists in the treatment
      of thrombotic conditions.

PMID- 12204638
TI  - Determination of bisphenol A in canned pet foods.
AB  - Bisphenol A (BPA) contamination of canned foods for human use has been studied,
      but there are no reports concerning BPA contamination of canned pet foods. The
      purpose of this study was to identify the levels of BPA in canned pet foods. A
      total of 26 samples (15 samples of cat food and 11 samples of dog food) were
      prepared for analysis by high-performance liquid chromatography. BPA in the
      samples was extracted with acetonitrile and fat in the sample extract was removed
      with hexane. Solid-phase extraction was used for sample clean-up prior to final
      analysis. The concentration of BPA ranged from 13 to 136 ng/g in canned cat food
      and from 11 to 206 ng/g in dog food. Also, to confirm that the BPA had originated
      from the can coating, distilled water was added to each washed empty can and the
      cans were autoclaved at 121 degrees C for 30 min. The concentration of BPA
      leached from empty cans was between 7 and 31 ng/ml.

PMID- 12204640
TI  - Serological investigation of aborted sheep and pigs for infection by Neospora
      caninum.
AB  - Serology for Neospora caninum was undertaken using direct ELISAs on sera from 660
      aborted sheep and 454 breeding sows, which had aborted or were considered
      infertile. All ovine sera were further tested by indirect fluorescent antibody
      test (IFAT) for N. caninum, and a latex agglutination test (LAT) for Toxoplasma
      gondii was performed on 423 of the samples, including all those positive by
      ELISA. ELISA-positive porcine sera were tested by IFAT and an inhibition ELISA
      for antibodies to N. caninum and by LAT for T. gondii. Only 3 (0.45%) of the
      ovine sera were seropositive for N. caninum by both ELISA and IFAT whereas
      although 40 porcine sera were seropositive by ELISA all were negative by IFAT.
      The results suggest that environmental exposure to N. caninum occurs rarely in
      sheep and pigs.

PMID- 12204639
TI  - Changes in activities of enzymes related to energy metabolism in peripheral
      leukocytes of diabetic dogs with glycemic control by intensive insulin treatment.
AB  - Changes in plasma glucose, immunoreactive insulin (IRI), and free fatty acids
      (FFA) concentrations and activities of enzymes related to energy metabolism in
      peripheral leukocytes were measured in type 1 diabetic dogs induced by
      streptozotocin administration before and after intensive insulin treatments.
      Before the insulin treatment, the plasma glucose concentrations were over 16.7
      mmol/L and the activities of enzymes remarkably decreased in leukocytes of the
      diabetic dogs. In particular, malate dehydrogenase (MDH) activities decreased
      significantly. After glycemic control was achieved by insulin treatment, the
      plasma glucose concentrations were maintained between 6.8 and 7.7 mmol/L and the
      activities of enzymes restored to those in the control dogs. The changes in ML
      ratio (cytosolic MDH/lactate dehydrogenase specific activity ratio) reflected
      faithfully to metabolic conditions of animals and were considered to be a useful
      parameter to evaluate glycemic control and the effect of injected insulin in the
      diabetic dogs.

PMID- 12204641
TI  - Plasma metabolites indicate energy metabolism disruption during the preclinical
      phase of bovine spongiform encephalopathy infection.
AB  - During the preclinical phase of bovine spongiform encephalopathy (BSE),
      significantly increased concentrations of lactic acid were measured in the blood
      of infected dairy cows. Other plasma metabolites, including alanine, leucine,
      serine, and glutamic acid, also showed significantly altered concentrations in
      the preclinical BSE animals compared to a control group. This appears consistent
      with the exaggerated stress response observed in clinical BSE, and precedes the
      development of clinical signs and overt behavioural changes. A number of other
      plasma metabolites including other amino acids and components of the plasma fatty
      acid content showed no association with BSE status.

PMID- 12204642
TI  - Basal nonselective cation permeability in rat cardiac microvascular endothelial
      cells.
AB  - The presence of a basal nonselective cation permeability was mainly investigated
      in primary cultures of rat cardiac microvascular endothelial cells (CMEC) by
      applying both the patch-clamp technique and Fura-2 microfluorimetry. With low
      EGTA in the pipette solution, the resting membrane potential of CMEC was -21.2 +/
      1.1 mV, and a Ca(2+)-activated Cl(-) conductance was present. When the
      intracellular Ca(2+) was buffered with high EGTA, the membrane potential
      decreased to 5.5 +/- 1.2 mV. In this condition, full or partial substitution of
      external Na(+) by NMDG(+) proportionally reduced the inward component of the
      basal I-V relationship. This current was dependent on extracellular monovalent
      cations with a permeability sequence of K(+) > Cs(+) > Na(+) > Li(+) and was
      inhibited by Ca(2+), La(3+), Gd(3+), and amiloride. The K(+)/Na(+) permeability
      ratio, determined using the Goldman-Hodgkin-Katz equation, was 2.01. The outward
      component of the basal I-V relationship was reduced when intracellular K(+) was
      replaced by NMDG(+), but was not sensitive to substitution by Cs(+). Finally,
      microfluorimetric experiments indicated the existence of a basal Ca(2+) entry
      pathway, inhibited by La(3+) and Gd(3+). The basal nonselective cation
      permeability in CMEC could be involved both in the control of myocardial ionic
      homeostasis, according to the model of the blood-heart barrier, and in the
      modulation of Ca(2+)-dependent processes.

PMID- 12204643
TI  - Impact of microscope numerical aperture on microspectrophotometric measurements
      of hemoglobin in microvessels.
AB  - In the microspectrophotometric method to measure hemoglobin concentration and
      oxygen saturation in microvessels it is recommended that a low numerical aperture
      (NA) condenser be employed to ensure that the recorded image is a true projection
      of the object. However, this tenet has never been rigorously justified. In this
      study, the microspectrophotometric method is evaluated using the theory of three
      dimensional image formation by a light microscope for a wide range of NA. The
      results of the calculations show that for measurements for hemoglobin
      concentration, the recorded image is close to the true projection only when the
      size of the microvessel is large compared to the degree of smearing (
      proportional, variant 1/NA) but small compared to the degree of defocus (
      proportional, variant NA(2)). These opposing tendencies lead to an optimum NA for
      which the errors are minimum. This optimum NA is a function of the size of the
      microvessel and the manner in which the hemoglobin concentration is distributed
      within the lumen. For measurements of oxygen saturation, the recorded image is
      the true projection as long as the measurements are made in regions near the
      microvessel centerline. For measurements made in regions away from the
      centerline, good agreement was obtained only when the distribution of oxygen
      saturation was uniform. Reconstruction of the axisymmetric profiles from the
      recorded projections showed that the errors in the projections cause the
      recovered profiles to deviate from the true profiles. These deviations are
      directly related to the extent by which the recorded projections deviate from the
      true projection.

PMID- 12204644
TI  - An orthotopic model for human uveal melanoma in SCID mice.
AB  - The microcirculation of primary uveal melanomas, their precursors, and their
      metastases is distinctive. Medium-sized and even large primary uveal melanomas
      typically lack significant zones of necrosis, suggesting that either these tumors
      are relatively well perfused or they are capable of growth in a severely blood
      deprived microenvironment. In addition to normal choroidal vessels that are
      incorporated into nevi and most primary uveal melanomas, aggressive primary and
      metastatic uveal melanomas tend to contain patterns of extracellular matrix that
      surround spheroidal or cylindrical packets of tumor cells. Some components of
      this branching, looping, and interconnected system of matrix may be perfused. It
      is now known that the generation of this patterning is a characteristic of
      genetically dysregulated melanoma cells (nonaggressive tumor cells do not form
      these patterns and melanomas lacking branching, looping, or interconnected matrix
      patterns tend to follow a relatively indolent course). We developed an orthotopic
      model of an aggressive human uveal melanoma by injecting suspensions of the
      primary human choroidal melanoma cell line (OCM1) into the subretinal space of
      one eye of 20 SCID mice. All mice were examined daily for tumor growth and tumors
      developed in every eye within 3 weeks of injection. The tumors were characterized
      by extraocular extension and the development of looping matrix patterns
      characteristic of those seen in aggressive human uveal melanoma. As in human
      uveal melanomas, these patterns were perfused by blood in areas. The orthotopic
      injection of human uveal melanoma cells into the SCID mouse eye generates a model
      reproducing the matrix-associated microcirculatory patterns of aggressive primary
      human uveal melanomas. This model can be used to explore the molecular
      pathogenesis and modulation of this novel circulation in vivo, to facilitate our
      understanding of the blood flow to these tumors providing insight into perfusion
      and drug delivery, to enable testing of pharmacologic modulation of pattern
      formation and intratumoral blood flow, and to refine noninvasive methods such as
      confocal scanning laser ophthalmoscopy to detect the presence of these patterns
      by which ophthalmologists might assess the biological behavior of tumors as
      noninvasive substitute for biopsy.

PMID- 12204645
TI  - Simultaneous recording of fingertip skin blood flow changes by multiprobe laser
      Doppler flowmetry and frequency-corrected thermal clearance.
AB  - We compared the results of skin blood flow (SBF) measurements, obtained
      simultaneously in adjacent fingertips by laser Doppler flowmetry (LDF) and
      thermal clearance (TC) probes, having approximately the same spatial and temporal
      characteristics. Experiments were performed in nine healthy volunteers during
      rest at room temperature (26-28 degrees C). A time resolution equal to about a
      second was achieved by speeding up the response of the thermal measurement
      circuit by applying the computer simulation software of the MATLAB package. The
      comparison revealed that the frequency-corrected TC signal correlated well with
      the multiprobe LDF signal (median correlation coefficient = 0.90, range = 0.84 to
      0.96). At the same time the individual slope values of the regression equation
      ranged from 0.58 to 1.61, revealing the difficulties encountered in obtaining the
      invariant scaling factor between the TC and LDF measurements. The relationship
      between the frequency-corrected TC signal and the multiprobe LDF signal was found
      to be linear in the range of SBF changes of about three- to fourfold. In the case
      of larger fluctuations in SBF, excessive acceleration at high SBF rates was
      noted.

PMID- 12204646
TI  - Effect of hemoglobin polymerization on oxygen transport in hemoglobin solutions.
AB  - The effect of hemoglobin (Hb) polymerization on facilitated transport of oxygen
      in a bovine hemoglobin-based oxygen carrier was studied using a diffusion cell.
      In high oxygen tension gradient experiments (HOTG) at 37 degrees C the diffusion
      of dissolved oxygen in polymerized Hb samples was similar to that in
      unpolymerized Hb solutions during oxygen uptake. However, in the oxygen release
      experiments, the transport by diffusion of dissolved oxygen was augmented by
      diffusion of oxyhemoglobin over a range of oxygen saturations. The augmentation
      was up to 30% in the case of polymerized Hb and up to 100% in the case of
      unpolymerized Hb solution. In experiments performed at constant, low oxygen
      tension gradients in the range of physiological significance, the augmentation
      effect was less than that in the HOTG experiments. Oxygen transport in
      polymerized Hb samples was approximately the same as that in unpolymerized
      samples over a wide range of oxygen tensions. However, at oxygen tensions lower
      than 30 mm Hg, there were more significant augmentation effects in unpolymerized
      bovine Hb samples than in polymerized Hb. The results presented here are the
      first accurate, quantitative measurements of effective diffusion coefficients for
      oxygen transport in hemoglobin-based oxygen carriers of the type being evaluated
      to replace red cells in transfusions. In all cases the oxygen carrier was found
      to have higher effective oxygen diffusion coefficients than blood.

PMID- 12204647
TI  - Lymphatic transport of pericardial effusate in sheep.
AB  - In this report, we quantified fluid loss from the pericardial cavity during
      simulated saline effusions and determined what proportion of this loss occurred
      through lymphatics. Fifty or 100 ml of Ringers lactate solution [containing 0.5%
      sheep albumin and (131)I-human serum albumin (HSA)] was injected into the
      pericardial cavity of sheep. Pericardial pressures, systemic arterial pressures,
      and plasma/pericardial fluid concentrations of the radioactive tracer were
      measured. Lymph transport of pericardial fluid was estimated from the plasma
      recovery of tracer using a mass balance equation. Plasma recoveries were
      corrected for tracer loss using a coefficient of elimination calculated from the
      plasma disappearance curve of intravenously administered (125)I-HSA. Over 4 h,
      27.6 +/- 4.9 (+/-SE) and 36.7 +/- 4.2 ml were lost from the pericardial cavity in
      the 50- and 100-ml effusion series, respectively, of which 5.2 +/- 0.8 (20.2 +/-
      3.8% of volume lost) and 7.7 +/- 1.6 ml (21.5 +/- 3.3% of volume lost) could be
      attributed to lymphatic transport. We conclude that lymphatic transport is one of
      the factors that contribute to pericardial "reserve" function by helping to
      restore pericardial fluid volume to resting levels.

PMID- 12204649
TI  - Feasibility of LDF measurements of optic nerve head blood flow in children with
      cerebral malaria.
AB  - The pathogenesis of cerebral malaria (CM), a significant cause of death in the
      tropics, is still not understood. Cerebral blood flow measurements would be
      important but are difficult under the conditions prevailing in CM clinics in the
      tropics. With the goal of using optic nerve head (ONH) blood flow (F(onh))
      instead of cerebral blood flow to help outcome prediction, we have tested the
      feasibility of performing F(onh) measurements in comatose CM children, using a
      portable ocular laser Doppler flowmeter (LDF). Measurements were performed in one
      eye of each of 13 children (2.7 +/- 1.1 years) during a period of about 8 min.
      The Vel(onh) (the relative blood velocity), Vol(onh) (the relative blood volume),
      and F(onh) values were determined for each child from three to five measurements
      of 2 to 20 s. Average Vel(onh), Vol(onh), and F(onh) values were 0.49 +/- 0.08
      kHz, 2.4 +/- 1.06 arbitrary units (a.u.), and 89 +/- 16.8 a.u., respectively. The
      average coefficients of variation of the flow parameters based on all segments in
      each child were 13 +/- 9% (range 1-29%) for Vel(onh), 27 +/- 13% (range 3-65%)
      for Vol(onh), and 23 +/- 12% (range 5-42%) for F(onh). This study demonstrates
      the feasibility of LDF measurements in CM children. The large range of these
      coefficients of variations could be due to the presence of fluctuations of ONH
      blood flow on a short time scale in these neurologically unstable children.

PMID- 12204648
TI  - Systemic effects of low-intensity laser irradiation on skin microcirculation in
      patients with diabetic microangiopathy.
AB  - Low-intensity laser irradiation has been shown to induce wound healing in
      conditions of reduced microcirculation, which is in part explained by systemic
      effects. We therefore investigated such a potential systemic effect of low
      intensity laser irradiation on skin blood circulation in patients with diabetic
      microangiopathy. Patients with diabetic microangiopathy were randomized to
      receive either a single helium-neon (HeNe, 632.8 nm) low-intensity laser
      irradiation with a dose of 30 J/cm(2) or a sham irradiation over the forefoot
      region in a double-blind, placebo-controlled clinical study. Skin blood
      circulation by means of temperature recordings over forefoot regions was detected
      by infrared thermography. Following a single transcutaneous low-intensity laser
      irradiation, a rise in skin temperature in both feet of the subjects in the laser
      group was noted, whereas in both feet of the subjects in the placebo group a drop
      in skin temperature occurred. The baseline-adjusted skin temperature 15 min after
      the end of the irradiation was significantly higher in the laser-treated forefeet
      compared to the placebo-"treated" forefeet (p < 0.0001); the baseline-adjusted
      difference in the temperature was 1.94 +/- 0.35 degrees C. Simultaneously, the
      baseline-adjusted skin temperature was significantly higher in the laser
      untreated forefeet compared to the placebo-"untreated" forefeet (P < 0.0001); the
      baseline-adjusted difference was 1.70 +/- 0.33 degrees C. Our data show a
      significant increase in skin circulation due to athermic laser irradiation in
      patients with diabetic microangiopathy and point to the possibility of inducing
      systemic effects.

PMID- 12204650
TI  - Adenosine enhances functional activation of blood flow in cat optic nerve head
      during photic stimulation independently from nitric oxide.
AB  - Blood flow studies in the brain, heart, and other organs suggest that there could
      be interaction between nitric oxide (NO) and adenosine. This possibility was
      investigated in the optic nerve head (ONH) during photic stimulation of the dark
      adapted cat eye. Functional activation of ONH blood flow was measured by laser
      Doppler flowmetry, simultaneously with NO and PO(2) using double-barrel recessed
      electrochemical sensors. Photic stimulation (diffuse luminance flickering light
      at 30 Hz) increased ONH blood flow to 127.4 +/- 4.7% (mean +/- SEM) of baseline
      with a transient increase in NO by 79.8 +/- 12.8 nM, while PO(2) decreased from
      24.5 +/- 2.7 to 22.7 +/- 2.4 Torr (control responses, 15 trials, 10 cats).
      Adenosine (3 mg/kg iv) increased baseline ONH blood flow to 113.8 +/- 8.4% of
      control within 5 min. Functional activation of ONH blood flow was enhanced during
      photic stimulation, reaching a maximum of 155.8 +/- 8.1% within 5 min, and
      remained enhanced for 30 to 45 min. NO responses during photic stimulation were
      not different from control responses. Treatment with a nonspecific NO synthase
      inhibitor (N(G)-nitro-L-arginine methyl ester, 40 mg/kg iv, 5 cats) did not alter
      the increase in resting ONH blood flow or the enhanced functional activation
      after adenosine. We conclude that there is no interaction between NO and
      adenosine during functional activation of cat ONH blood flow by photic
      stimulation.

PMID- 12204651
TI  - Oxidative stress and cardiac microvascular structure in ischemia and reperfusion:
      the protective effect of antioxidant vitamins.
AB  - Reperfusion of the ischemic myocardium results in structural changes in the
      capillary bed, which may contribute to decreased microcirculatory flow ("no
      reflow"). This study was designed to correlate the endothelial cell shape changes
      with both oxidative stress and lipid peroxidation and to evaluate the beneficial
      potential of Trolox (a hydrophilic analogue of alpha-tocopherol) and ascorbic
      acid. Isolated buffer-perfused rat hearts were made ischemic for 45 min and then
      reperfused with 100 microM Trolox and/or 100 microM ascorbic acid. Morphological
      changes were quantified by measuring capillary cross-sectional areas. Increased
      myocardial content of oxidized glutathione and its release into the coronary
      effluent were used as indices of oxidative stress. Myocardial MDA, an end product
      of lipid peroxidation, was also measured. Luminal membrane blebs and capillary
      "constriction" in the ischemic groups occurred when there was no change in either
      glutathione status or MDA concentrations. Reperfusion altered the redox state of
      the heart sufficiently to induce lipid peroxidation. It also induced endothelial
      cell swelling and a reduction in luminal area. Ascorbic acid was a more effective
      antioxidant than Trolox as it significantly reduced both oxidative stress and
      ultrastructural injury. The combined antioxidant treatment returned both the
      stress ratio and the capillary measurements to control values. We conclude that
      endothelial cell swelling correlates with the degree of oxidative stress and that
      antioxidant vitamins reduce membrane damage by preventing lipid peroxidation.

PMID- 12204652
TI  - Cultivation and characterization of coronary microvascular endothelial cells: a
      novel porcine model using micropigs.
AB  - Coronary microvascular endothelial cells (CMECs) play an important role in many
      physiological processes. Porcine CMECs from large breed pigs have been isolated
      and successfully cultured. However, because micropigs offer research advantages
      over large breed pigs, micropig CMEC (MPCMEC) cultures may be useful as an
      alternative in vitro porcine model for cardiovascular studies. We isolated
      MPCMECs from six Panepinto micropigs using a simplified technique and developed a
      system for their successful culture. MPCMECs were isolated by collagenase
      digestion of left ventricular samples obtained using sterile techniques. Primary
      isolates of MPCMECs grew steadily in complete DMEM supplemented with 20% FBS, 4
      mM MgSO(4), and 500 microM dibutyryl cAMP and reached confluence in 7-10 days.
      Endothelial origin was demonstrated by rapid (4-h) uptake of acetylated low
      density lipoprotein, immunostaining for the presence of platelet/endothelial cell
      adhesion molecule-1 (PECAM-1, CD31), von Willebrand factor (vWf)-related antigen,
      vascular endothelial cadherin (VE-cadherin), endothelial nitric oxide synthase
      (eNOS), and by positive staining using two fluorescein isothiocyanate-labeled
      endothelial-specific lectins, Dolichos biflorus agglutinin and Ulex europaeus
      agglutinin-1. MPCMECs also exhibited immunostaining for alpha-smooth muscle
      actin. MPCMECs were successfully subcultured in the absence of dibutyryl cAMP and
      continued to express PECAM-1 and vWf, but not eNOS, to passage six. The typical
      morphology of subconfluent MPCMECs consisted of elongated cells that grew in a
      swirling, herringbone pattern.

PMID- 12204653
TI  - Ultrastructure of absorbing peripheral lymphatic vessel (ALPA) in guinea pig
      Peyer's patches.
AB  - Corrosion casts from neoprene direct injection of lymphatic and blood vessels in
      guinea pig gut-associated lymphoid tissue, that is, solitary lymphoid follicles
      and Peyer's patches, have shown both their numerical density and their
      topographical arrangement in physiological conditions, after starvation and
      lymphatic stasis. The absorbing peripheral lymphatic vessel (ALPA) begins with
      the lacteal vessel, which continues in the mucosal lymphatic network. The latter
      is formed by subepithelial and interfollicular vessels wrapping single lymphoid
      follicles like a basket. Interfollicular vessels drain in the submucosal network,
      which flows into muscular tunica vessels with nonsegmentary bicuspid valves. They
      in turn drain lymph in subserosal precollectors and then in prelymphonodal
      collectors with conduction function. The follicles' germinal center and dome are
      completely devoid of ALPA vessels, while they are rich in blood vessels.
      Ultrastructurally, the ALPA vessel wall consists of a monolayer of endothelial
      cells devoid of pores, fenestrations, and open junctions and lacking a continuous
      basal lamina. Endothelial cells are joined by overlapping and interdigitating
      intercellular contacts, while end-to-end contacts are rare. They have a sizeable
      cell body, containing the nucleus and the common endocytoplasmic organelles, and
      a peripheral cytoplasm with actin-like filament bundles, free microvesicles or
      forming channels and a few rough-surfaced encloplasmic reticulum (RER)
      canaliculi. The presence of intraendothelial channels crossed by lymphocytes can
      often be detected within the endothelial wall during the different phases of cell
      transendothelial migration from lymphoid tissue to lymphatic vessel lumen. These
      channels undergo a numerical increase during starvation, while they are scarce
      during lymphatic stasis. We have quantitatively evaluated the prevalence of T
      lymphocytes in the lymph of interfollicular ALPA vessels and of prelymphonodal
      collectors draining the small intestine tract with or without Peyer's patches,
      under physiological and experimental conditions (starvation, lymphatic stasis).

PMID- 12204654
TI  - Isolation and characterization of large numbers of endothelial cells for studies
      of cell signaling.
AB  - Studies of endothelial cell signaling involving cholesterol-rich domains require
      large numbers of cells of bona fide origin. The growth of any cell in culture,
      particularly for extended periods, results in an altered phenotype that could
      include changes in the properties of caveolae and lipid raft structures. While
      continuously propagated cells are used to study specific questions because their
      origin is known and because proteins of interest are still expressed, such
      reasoning is an oversimplification and can lead to findings that are descriptive
      of the cell's adaptation to culture rather than its original phenotype. We are
      particularly cognizant of this concern as we examine caveolar signaling domains
      in endothelial cells. Here we present a reproducible method for the isolation and
      characterization of large numbers of bona fide endothelial cells suitable for
      studies of the regulation of receptor signal transduction. Digestion of guinea
      pig hearts with collagenase results in the liberation of cells that adhere to
      collagen-coated plastic and express platelet-endothelial cell adhesion molecule 1
      (PECAM-1) and binding sites for Ulex europaeus agglutinin 1 (UEA-1) that permit
      segregation of cells using fluorescence-activated cell sorting. Growth of cells
      over 7 doublings results in enrichment in the expression of both PECAM-1 and UEA
      1 and retention of functional low-density lipoprotein receptor. The ability of
      cells to differentiate into endothelial tubes at any stage during their
      characterization up to 20 doublings in culture suggests that this method can be
      employed to generate endothelial cells that are minimally altered from their site
      of origin.

PMID- 12204655
TI  - Study of platelet behavior in vivo after endothelial stimulation with laser
      irradiation using fluorescence intravital videomicroscopy and PEGylated liposome
      staining.
AB  - Platelets contain an array of potent proinflammatory mediators, and therefore
      they are regarded as mediator and effector cells in inflammation. Knowing the
      role of platelets during these processes is crucial and the analysis of their
      behavior in situ and the associated mechanisms is consequently particularly
      important. However, conventional in vitro staining techniques induce modification
      of the characteristics of platelets. This study aimed to evaluate platelet
      behavior in vivo after endothelial stimulation (without endothelial denudation or
      exposure of basal lamina and/or collagen) with an argon laser, using video
      intravital microscopy in combination with a new an innovative platelet staining
      technique based on polyethyleneglycol (PEG) liposomes. The study was performed on
      skin by using a dorsal skin-fold chamber implanted in golden hamsters. Platelets
      were stained by 5,6-CF-encapsulated PEGylated liposomes injected intravenously.
      The skin microcirculation was observed with an intravital microscope (using x25,
      x40, and x80 magnifications) fitted with a xenon light source, an epifluorescence
      assembly, and an ultra-high sensitivity video camera for fluorescence imaging.
      Platelet activation without endothelial denudation or exposure of basal lamina
      and/or collagen was obtained with an argon laser emitting at 514.5 nm with the
      following parameters: 20 mW, 300 ms, 120 J/cm(2). The 80-microm laser beam was
      focused on a vessel and its position was controlled with the microscope. Thanks
      to the spatial resolution of the intravital microscopic imaging system, the
      platelets were seen rolling individually on the endothelium. After laser
      stimulation, platelets were activated and three phases were observed:
      recruitment, adhesion and detachment. The observation of these three phases was
      time dependent and the kinetics of the process were quantified. The recruitment
      reached a maximum after 90 +/- 20 s. The adhesion phase lasted for 110 +/- 25 s.
      At last, detachment of all platelets was observed. This detachment started 200 +/
      20 s after irradiation and was completed in less than 2 min. This study confirms
      that laser irradiation used with optimal parameters can induce platelet
      activation without thrombus formation. Platelets can adhere only transiently on
      stimulated endothelium. This phenomenon may therefore represent a defense
      mechanism, by which platelets would accumulate in the vicinity of an injury,
      making them available for immediate response. At last, this study has clearly
      demonstrated the advantages of our new and innovative platelet staining method
      using PEGylated liposomes, which are (i) in situ labeling, (ii) use of a
      hydrophilic marker located in an aqueous compartment within the platelet, and
      (iii) labeling of platelets allowing observation during the whole experiment.

PMID- 12204656
TI  - Erythropoietin and VEGF exhibit equal angiogenic potential.
AB  - Erythropoietin (Epo) is a hormone regulating proliferation and differentiation of
      erythroid cells. The hypothesis that hematopoietic and endothelial cells share a
      common hemangioblast progenitor among others is based on the finding that both
      cell lineages express cell surface antigens like CD31 and CD34. In this study we
      investigated the angiogenic potential of recombinant human erythropoietin
      (rHuEpo) on endothelial cells derived from human adult myocardial tissue. In
      addition, we compared the angiogenic potential of rHuEpo to that of other
      cytokines (VEGF, aFGF) and combinations of growth factors. Samples of myocardial
      tissue (cardiac auricle) were obtained during coronary bypass surgery, embedded
      in a fibrin gel matrix, and cultured for 21 days. Capillary sprouting was
      measured with an eye-piece graticule under an inverted-phase contrast microscope.
      Tube-forming endothelial cells were characterized by immunohistochemistry and RT
      PCR. Using a concentration of 2.5 U/ml, we found that rHuEpo stimulates capillary
      outgrowth up to 220%, compared to the nonstimulated physiological outgrowth. Epo
      therefore exhibits the same angiogenic potential on endothelial cells in our in
      vitro assay as VEGF(165) (230% increase). Erythropoietin stimulates capillary
      outgrowth in an in vitro angiogenesis assay using adult human myocardial tissue.
      This implies a role of erythropoietin in vasoproliferative processes. rHuEpo may
      serve as a direct angiogenic substance in patients with ischemic heart disease.

PMID- 12204657
TI  - Apoptosis causes lumen formation during angiogenesis in vitro.

PMID- 12204658
TI  - Calcium-induced calcium release and cyclic ADP-ribose-mediated signaling in the
      myocytes from small coronary arteries.

PMID- 12204659
TI  - 20-HETE pathway antagonists inhibit rat small mesenteric artery tone.

PMID- 12204660
TI  - Ischemia-reperfusion does not cause significant hyaluronan depolymerization in
      skeletal muscle.
AB  - The size of hyaluronan in lymph and gastrocnemius muscle was measured to test the
      hypothesis that reperfusion of ischemic skeletal muscle leads to hyaluronan
      depolymerization. Prenodal lymph was collected from the gastrocnemius muscle in
      anesthetized rabbits. Hyaluronan size was measured using a combination of agarose
      gel electrophoresis and a radiometric assay. In control legs, muscle contained
      primarily high-molecular-weight hyaluronan (greater then 4 x 10(6)), while lymph
      contained primarily low-molecular-weight hyaluronan (less than 0.79 x 10(6))
      which was absent from tissue. Following 3 h of ischemia and 8 h of reperfusion,
      the lymph flux for high-molecular-weight hyaluronan was 25 times the value from
      the control leg. Neither the size nor the content of hyaluronan in tissue
      decreased. Muscle albumin content from the reperfused leg was 2.3 times the value
      from the control leg, while lymph albumin flux was 4 times the control value.
      Measurements following 24 h of reperfusion confirmed the absence of changes in
      the size or content of hyaluronan in tissue although an increased albumin content
      and wet weight-to-dry weight ratio indicated sustained edema. The daily removal
      of hyaluronan by lymph was calculated to be 2-3% of the tissue content. Since the
      lymph drainage of hyaluronan represented only a very small fraction of tissue
      hyaluronan, the amount of depolymerization was too small to produce significant
      changes in the tissue.

PMID- 12204661
TI  - Tumour viruses--could they be an Achilles' heel of cancer?

PMID- 12204662
TI  - Measuring the clinical response. What does it mean?
AB  - The clinical response to treatment is an important indicator of the therapeutic
      effect of anticancer agents. Its value and interpretation has to be carefully
      considered within the context that it is used. In daily practice, response
      assessment is combined with other indicators of the patient's condition to
      contribute to the decision-making process. In clinical trials, it is widely used
      to identify and quantify the anti-tumour activity of new agents. In this context,
      response evaluation is conducted on the basis of strict predefined criteria such
      as the World Health Organization (WHO) or Response Evaluation Criteria In Solid
      Tumors (RECIST) criteria. The RECIST criteria have recently been proposed and
      offer a detailed guidance to perform a response evaluation. Clinical response is
      also used as an indicator of therapeutic efficacy in combination with other
      indicators. Its value as a surrogate indicator of a survival benefit remains
      unclear in most instances and can hardly be established within the framework of a
      single randomised trial. With the development of new anticancer agents that
      behave differently to cytotoxics, clinical benefit will have to integrate
      concepts of disease stabilisation or time to progression. Over the next decade,
      oncologists will be able to assess the biological response before the clinical
      response, and a lot of work and energy will have to be dedicated to assess the
      predictive and, possibly, the prognostic value of the biological response with
      regard to the clinical response, as well as more definitive measures of clinical
      benefit.

PMID- 12204663
TI  - Health related quality of life assessment methodology and reported outcomes in
      randomised controlled trials of primary brain cancer patients.
AB  - Over the last 20 years, the assessment of quality of life (QOL) has become an
      important endpoint in cancer clinical trials, helping us to understand patient
      survival and QOL experiences and aiding clinicians in providing the best possible
      treatment and care, with the least toxicity and ill-effects. In primary brain
      cancer, these are critical issues. Survival is often limited and treatment
      difficult to tolerate. In recent years, some authors have questioned the
      methodological quality of the investigations and the reporting of QOL assessments
      from randomised controlled trials (RCTs), of cancer patients yet this assessment
      has never specifically focused on brain cancer. This paper therefore reports a
      systematic review of the research methodology and QOL assessment reporting in
      brain cancer patients in RCTs. The search was mainly performed on the following
      databases: Medline, Cancerlit and the Cochrane Controlled Trials Register. We
      identified only five RCTs, enrolling a total of 1026 patients. In many of these
      studies, we had identified methodological limitations which would hinder the
      interpretation of the results. These included a lack of detailed reporting
      regarding missing data, use of poorly validated tools, and general limitations
      regarding the presentation and interpretation of the results. Based on the
      results of our review, we make recommendations for future investigations to avoid
      these shortcomings.

PMID- 12204664
TI  - Current status and future prospects for the treatment of chemotherapy-induced
      peripheral neurotoxicity.

PMID- 12204665
TI  - p107 Expression in colorectal tumours rises during carcinogenesis and falls
      during invasion.
AB  - p107 Links to cyclin A/CDK2 (cyclin-dependent kinase 2) and cyclin E/CDK2 that
      are important cell cycle regulators. However, p107 expression remains unclear in
      almost all kinds of human solid tumours. To clarify the expression of p107 in
      colorectal tumours, 22 normal mucosae, 9 hyperplastic polyps, 60 adenomas, 198
      primary carcinomas, 21 lymph-nodal metastases, and 10 hepatic metastases were
      immunohistochemically stained for p107, cyclin A, cyclin E, CDK2 and Ki67.
      Results were measured using labelling indices (LIs). p107 LIs surpassed the
      highest value in normal tissues in six of nine hyperplastic polyps, 54 of 60
      adenomas, 144 of 198 primary cancers, 13 of 21 nodal foci and three of 10 hepatic
      foci. p107 LIs also apparently rose from normal through hyperplasia and adenoma
      to early carcinoma. However, they declined in liver-metastatic foci, and in
      primary cancers showing large size, mucinous type, venous invasion, lymphatic
      invasion, poorly differentiated type, deep invasion, lymph-nodal metastasis,
      hepatic metastasis or advanced stage. Low p107 LIs were also linked to a poor
      survival, particularly in stage-III patients. As the p107 LI gradually rose, the
      CDK2 (in primary cancers only), cyclin A, cyclin E and Ki67 LIs were elevated
      concurrently-in both adenomas and primary cancers. Thus, in colorectal tumours,
      p107 expression rises abnormally and gradually during carcinogenesis and then
      falls during invasion, and thereby probably perturbs the cell-cycle control and
      promotes carcinogenesis and invasion. Clinically, reduced p107 may indicate a
      poorer prognosis.

PMID- 12204667
TI  - Tamoxifen beyond 5 years--patients' decisions regarding entry to the aTTom trial.
AB  - The aim of this study was to assess among a population of women who had taken
      adjuvant tamoxifen for 5 years, how many were prepared to enter a randomised
      trial looking at the duration of tamoxifen treatment and what was the preference
      of those who declined trial entry. There is uncertainty as to the optimum
      duration of adjuvant tamoxifen and this is the subject of the aTTom (adjuvant
      Tamoxifen Treatment offer more?) trial in which patients are randomised to
      continue or stop tamoxifen after 5 years. Patients have been recruited to the
      aTTom trial in Dundee since 1996 and a record has been kept of all the patients
      with whom the trial was discussed. Patients who declined trial entry were allowed
      to choose whether to electively stop or continue tamoxifen. 306 patients were
      eligible for trial entry of whom 171 (56%) consented to randomisation (82 to
      continue and 89 to stop). Amongst the 135 (44%) who declined randomisation, 28
      (21%) elected to stop tamoxifen treatment, 90 (67%) elected to continue and in 17
      (13%) their decision was unclear. These results illustrate that patients eligible
      for the aTTom trial share our clinical equipoise. A majority (56%) of patients
      were agreeable to randomisation, but among those who declined, some (67%)
      preferred to continue, some (21%) to stop tamoxifen. This trial is unusual in
      that the patients have already experienced the treatment options, so the
      patients' preferences reflect a truly informed choice.

PMID- 12204666
TI  - Quality assurance in the EORTC 22921 trial on preoperative radiotherapy with or
      without chemotherapy for resectable rectal cancer: evaluation of the individual
      case review procedure.
AB  - The aim of this study was to assess any inconsistency with the protocol
      guidelines for preoperative radiotherapy for rectal cancer among radiotherapy
      institutions participating in the framework of a multicentre phase-III European
      Organization for Research and Treatment of Cancer (EORTC) clinical trial. Twelve
      radiotherapy departments with more than 10% of the evaluable patients recruited
      in the trial, were invited to participate in this individual case review.
      Participating institutions were asked to send five full patient records with the
      chemotherapy charts, surgical and pathology reports, radiation treatment charts,
      treatment planning calculations, computed tomography (CT) scans, portal images
      and follow-up charts. The sample of the 5 patients per institution was randomly
      selected at the EORTC Data Center. All 12 departments participated. In 21 (35%)
      of the cases, a three-field technique with two lateral opposed wedge fields and a
      posterior field was used, while in 39 (65%) of the cases a four-field pelvic box
      technique was used. All participants used linear accelerators with a minimum of 6
      MeV photon-beam energy. In general, the patients were eligible, documentation of
      clinical data was fair to good and there were no systematic major protocol
      deviations. The actual total dose was 44.7+/-a standard deviation (S.D.) of 4.6
      Gy. Some variation was found in the fraction size. All institutions complied with
      the protocol in specifying the reference dose at the ICRU point. The clinical
      target volume (CTV) drawn on the CT scan was narrow in 7 (12%) cases, but
      eventually the actually treated volumes in terms of planned treatment volume
      (PTV) were correct. In two institutions, although the CTV was drawn correctly,
      the fields appeared to be narrow especially in cranio-caudal direction.
      Variations in treated volumes and total radiation dose were encountered in the
      individual case review. By providing recommendations early during the course of
      the trial, we expect to improve the inter-institutional consistency and to
      promote a high quality treatment in all of the participating institutions.

PMID- 12204668
TI  - Local recurrence in the breast after conservative surgery--a study of prognosis
      and prognostic factors in 391 women.
AB  - In a population-based cohort of 6613 women with invasive breast cancer, who had
      breast-conserving surgery between 1981 and 1990, 391 recurrences in the operated
      breast were identified. The main aim of this study was to examine the prognosis
      and prognostic factors in different subgroups of local recurrences, characterised
      by the time to recurrence, location of recurrence and previously given
      radiotherapy. The median follow-up for women who had a local recurrence was 7.9
      years. The life-table estimates for breast cancer-specific survival in women with
      local recurrences were 84.5% (standard error (S.E.) 1.8) at 5 years and 70.9%
      (S.E. 2.7) at 10 years. The risk of breast cancer death was highest among women
      who had an early (<or=2 years) recurrence in the same quadrant as the primary
      tumour, with a breast cancer-specific survival of 67.9% (S.E. 4.8) at 5 years and
      56.0% (S.E. 5.9) at 10 years. There was a statistically significant difference in
      the probability of breast cancer-specific survival, as measured from the
      recurrence, between women who initially did or did not receive radiotherapy
      (P=0.0123). However, when measured from primary treatment, there was no
      significant difference, indicating that the difference in prognosis could be due
      to a lead-time bias. Independent prognostic factors for breast cancer-specific
      survival in women with local recurrences were time to local recurrence and the
      Nottingham Prognostic Index (NPI).

PMID- 12204669
TI  - Phase I and pharmacokinetic study of paclitaxel and irinotecan for patients with
      advanced non-small cell lung cancer.
AB  - We conducted a phase I study of paclitaxel and irinotecan (CPT-11) in advanced
      non-small cell lung cancer (NSCLC). This study aimed to determine the maximum
      tolerated doses (MTD). The pharmacokinetics of CPT-11 and its major active
      metabolite, SN-38, were also analysed. Patients received paclitaxel (day 1)
      followed by CPT-11 (days 1, 8 and 15), in a 4-week cycle, and paclitaxel and CPT
      11 were escalated from 120 and 40 mg/m(2), respectively. 28 patients were
      enrolled, who were evaluated for toxicity. 2 of 6 patients at 210 mg/m(2)
      paclitaxel and 50 mg/m(2) CPT-11, and 2 of 4 at 180 and 60 mg/m(2) developed dose
      limiting toxicity (DLT) (neutropenia, fever, neurotoxicity and diarrhoea). The
      area under the plasma concentration-time curve (AUC) of CPT-11 on day 1 was
      significantly higher than that on days 8 or 15 at each dose level (P=0.002). The
      AUC of SN-38 on day 1 was significantly increased using paclitaxel doses >or=150
      mg/m(2). A preceding paclitaxel administration changed the pharmacokinetics of
      CPT-11 and SN-38. However, the toxicity was tolerable. Paclitaxel 180 mg/m(2) and
      CPT-11 50 mg/m(2) were the recommended doses for further phase II study of this
      combination.

PMID- 12204670
TI  - Variation in MT expression in early-stage depressed-type and polypoid-type
      colorectal tumours.
AB  - Metallothionein (MT) expression is observed in various carcinomas, but its role
      is not fully understood. To clarify the clinicopathological significance of MT,
      87 colorectal adenomas and 128 early-stage carcinomas were immunohistochemically
      analysed for MT expression. The degree of MT immunostaining of a specimen was
      graded according to the proportion of MT-positive cells; negative (<5%) and
      positive (focally 5-50%, diffusely >50%). MT expression significantly decreased
      with tumour development. For carcinomas, MT-positivity was significantly
      associated with depth of invasion (T1 60% versus T2 33%; P<0.01), vascular
      involvement (positive 35% versus negative 61%; P<0.01) and morphology (polypoid
      62% versus depressed 26%; P<0.01). Regarding MT-positive distribution, the
      diffuse-positive rate in MT-positive polypoid lesions was 28%, while MT-positive
      depressed lesions were all diffusely stained (P<0.01). In conclusion, our results
      suggested that decreasing MT expression is an early event in colorectal
      carcinogenesis and may reflect local invasion. Furthermore, MT-positive
      distribution may reflect genetic differences between the polypoid and depressed
      type.

PMID- 12204672
TI  - Palliative care in paediatric oncology.

PMID- 12204671
TI  - Topotecan preceded by oxaliplatin using a 3 week schedule: a phase I study in
      advanced cancer patients.
AB  - Combinations of topoisomerase I (topo I) poisons and platinum derivatives have
      synergistic antitumoral effects. However, their clinical development is limited
      by supra-additive haematological toxicity. The aim of this study was to determine
      whether sustained doses of topotecan and oxaliplatin could be achieved using a
      synergistic sequence. 34 advanced cancer patients and 186 cycles were evaluable
      for toxicity over five dosing levels. Oxaliplatin at 85-110 mg/m(2) was given on
      day 1, followed by topotecan 0.5-1.25 mg/m(2)/day x 5 from day 1 to 5, every 3
      weeks. Plasma pharmacokinetics (PK) of total and ultrafiltrable platinum, total
      and lactone forms of topotecan were determined in the first cycle. The dose
      limiting toxicity (DT) was identified as grade 4 thrombocytopenia. The occurrence
      of grade 4 thrombocytopenia did not correlate with topotecan PK, but it did with
      the patient's characteristics. Severe thrombocytopenia was seen in 1/8 of
      patients without clinical or biological evidence of malnutrition, with a
      creatinine clearance higher than 1 ml/s, and no more than two previous
      chemotherapy regimens, while it was seen in 8/10 patients with one of these
      characteristics (P<0.004). In conclusion, the recommended doses of oxaliplatin
      110 mg/m(2) and topotecan 1 mg/m(2)/day, every 3 weeks can be administered to
      patients with a favourable general status and pretreatment characteristics and a
      phase II study is worthwhile in ovarian cancer patients.

PMID- 12204674
TI  - Distinct prevalence of the CYP19 Delta3(TTTA)(7) allele in premenopausal versus
      postmenopausal breast cancer patients, but not in control individuals.
AB  - The CYP19 gene encodes the enzyme aromatase, which plays a key role in the
      conversion of androgens to oestrogens. A polymorphism in CYP19 in intron 4
      (TTTA)n has been reported to be associated with breast cancer (BC) risk, although
      conflicting evidence has also been published. Here, we employ a non-traditional,
      highly demonstrative design of a molecular epidemiological study, where the
      comparison of BC cases and healthy middle-aged female donors was supplemented by
      an analysis of groups with extreme characteristics of either BC risk (bilateral
      breast cancer (biBC) patients) or cancer tolerance (tumour-free elderly women
      aged >or=75 years). None of the (TTTA)n polymorphic variants was significantly
      overrepresented among the affected women compared with any of the control groups.
      However, a 3-bp deletion/insertion CYP19 polymorphism, which is located in the
      same intron approximately 50 bp upstream to the (TTTA)n repeat, was evidently
      associated with the menopausal status in both the BC and biBC cohorts. In
      particular, the Delta3(TTTA)(7) allele occurred significantly more frequently in
      premenopausal than in postmenopausal BC patients (65/172 (38%) versus 67/310
      (22%); P=0.0001; Odds Ratio (OR)=2.20 (95% Confidence Interval (CI) 1.46-3.32)),
      while the perimenopausal cases demonstrated an intermediate value (9/34 (26%)).
      In the biBC cohort, women who developed both tumours during their premenopausal
      period had a significantly higher prevalence of the Delta3(TTTA)(7) allele than
      patients with a postmenopausal onset of bilateral disease (16/46 (35%) versus
      8/50 (16%); P=0.035; OR=2.80 (1.08-7.23)); those biBC patients, whose tumours
      were diagnosed before and after the cessation of menses, displayed an
      intermediate occurrence of the Delta3(TTTA)(7) allele (7/32 (22%)). Similar
      tendencies in the Delta3(TTTA)(7) allele distribution in BC and biBC patients
      suggest that its association with the menopausal status of the patients is truly
      non-random and thus this observation deserves further detailed investigation.

PMID- 12204675
TI  - The therapeutic efficacy of adenoviral vectors for cancer gene therapy is limited
      by a low level of primary adenovirus receptors on tumour cells.
AB  - Replication-defective adenoviral vectors are currently being employed as gene
      delivery vehicles for cancer gene therapy. To address the hypothesis that the
      therapeutic efficacy of adenoviral vectors is restricted by their inability to
      infect tumour cells expressing low levels of the primary cellular receptor for
      adenoviruses, the coxsackievirus and adenovirus receptor (CAR), we have employed
      a pair of ovarian cancer cell lines differing only in the expression of a primary
      receptor for Ad5. This novel system thus allowed the direct evaluation of the
      relationship between the efficacy of an adenoviral vector and the primary
      receptor levels of the host cancer cell, without the confounding influence of
      other variable cellular factors. We demonstrate that a deficiency of the primary
      cellular receptor on the tumour cells restricts the efficacy of adenoviral
      vectors in two distinct cancer gene therapy approaches, TP53 gene replacement
      therapy and herpes simplex virus thymidine kinase/ganciclovir suicide gene
      therapy. Moreover, we show that a deficiency of the primary receptor on the
      tumour cells limits the efficiency of adenovirus-mediated gene transfer in vivo.
      Since a number of studies have reported that primary cancer cells express only
      low levels of CAR, our results suggest that strategies to redirect adenoviruses
      to achieve CAR-independent infection will be necessary to realize the full
      potential of adenoviral vectors in the clinical setting.

PMID- 12204676
TI  - RhCG is downregulated in oesophageal squamous cell carcinomas, but expressed in
      multiple squamous epithelia.
AB  - To better understand the molecular events underlying the development of
      oesophageal cancer, we have isolated the genes dysregulated in primary
      oesophageal cancer tissues using a modified differential display polymerase chain
      reaction (DD-PCR). In the present study, a gene designated C15orf6 was
      identified. The C15orf6 gene, encompassing 25 kb, is composed of 11 exons with a
      mRNA of 1948 bp. Database searching showed that C15orf6 was 100% homologous to
      the Rh type C-glycoprotein (RhCG) with the same open reading frame, but 16 bp
      longer than RhCG at the 5'-end. The gene was highly expressed in human
      oesophagus, cervix, oral cavity, skin and kidney, but undetectable in the other
      14 adult normal tissues examined. Northern blot, RT-PCR and western blot analysis
      showed that RhCG/C15orf6 was frequently lost or dramatically reduced in primary
      oesophageal cancer tissues (30/34) compared with the corresponding normal
      oesophageal mucosa. Three oesophageal-cancer cell lines tested lacked
      RhCG/C15orf6 expression. Immunohistochemistry revealed that in normal oesophageal
      tissues, RhCG/C15orf6 was mainly expressed in the plasma membrane of the
      epithelial cells. In addition, Rh-associated glycoprotein (RhAG) expression was
      also commonly silenced in both oesophageal cancer cell lines (2/3) and primary
      oesophageal cancer tissues (11/13). To our knowledge, this is the first time that
      RhAG expression has been seen in oesophageal epithelium and extends the
      functional role of the RhAG protein beyond the erythrocyte. These data suggest
      that inactivation of RhCG/C15orf6 and RhAG occurs frequently during the
      development of human oesophageal cancer.

PMID- 12204677
TI  - Cells obtained from colorectal microadenomas mirror early premalignant growth
      patterns in vitro.
AB  - LT97, a permanent cell line consisting of epithelial cells with an early
      premalignant genotype was established from small colorectal polyps. LT97 cells
      have lost both alleles of the APC tumour suppressor gene. In addition, they carry
      a mutated Ki-ras oncogene, while TP53 is normal. LT97 growth characteristics are
      thus representative of early adenomas. They had to be passaged as multicellular
      aggregates indicating a dependency of survival on cell-cell contact and in
      accordance with their premalignant genotype were not capable of growth in soft
      agar. LT97 cells did express both the EGF-receptor and small amounts of
      TGF(alpha) establishing an autocrine growth or survival pathway. However, in
      spite of autocrine TGF(alpha) production, growth was strongly dependent on
      exogenous growth factors--mainly EGF, insulin and HGF. Inhibition of the EGF
      receptor kinase induced apoptosis at an IC(50) concentration of 4 micromolar
      indicating that TGF(alpha) activated survival pathways in the early adenoma cell.

PMID- 12204678
TI  - Differing expression of enzymes of the glyoxalase system in superficial and
      invasive bladder carcinomas.
AB  - This work aimed to study the activities of the glyoxalase system enzymes
      (glyoxalase I (GI) and glyoxalase II (GII) and their gene expression in human
      bladder carcinomas compared with the corresponding normal mucosa. Samples of
      these tissues were collected from 26 patients with superficial (SBC) or invasive
      bladder cancer (IBC) and used to evaluate enzyme activity and gene expression by
      northern blot analysis. In keeping with the electrophoretic pattern and the
      expression level of the respective genes, GI activity significantly increased in
      SBC samples, while it remained unchanged in IBC samples compared with the normal
      mucosa. In contrast, GII showed a higher activity in the tumour (either SBC or
      IBC samples) versus normal tissues. These results confirm the role of the
      glyoxalases in detoxifying cytotoxic methylglyoxal (MG) in bladder cancer. The
      differing levels of GI activity level and gene expression of GI between the SBC
      and IBC samples could help in their differential diagnosis.

PMID- 12204679
TI  - Heterogeneity of vascularisation in invasive breast carcinoma.

PMID- 12204680
TI  - Kosan biosciences. Better chemistry through genetics.

PMID- 12204681
TI  - Aptamer rivalry.
AB  - A controllable, intracellular RNA aptamer could be an invaluable therapeutic or
      discovery reagent. A report published in this journal shows that aptamer behavior
      can be regulated by a small molecule, paving the way for the development of more
      sophisticated ligand-regulated aptamers.

PMID- 12204683
TI  - Battle for the bulge: directing small molecules to DNA and RNA defects.
AB  - Small molecules were tailored to specifically bind bulged DNA by complementing
      the geometry and nucleotide size of the bulge site. The prospect of generating
      small molecules that influence the secondary structure of DNA and RNA holds great
      promise for clinical applications.

PMID- 12204682
TI  - Discovering antimalarials: a new strategy.
AB  - Recent discoveries have uncovered some key processes that occur in the food
      vacuole of the malarial parasite. Consequently, new families of potential
      antimalarials that inhibit HRP-2, a hitherto unexplored drug target, were
      identified using a novel screening method.

PMID- 12204684
TI  - Reflections on a novel therapeutic candidate.
AB  - Aptamers composed of L-nucleic acids, Spiegelmers, were selected to specifically
      bind GnRH. Spiegelmer inhibition of GnRH activity was demonstrated in both
      cellular and animal models. Rabbit studies showed minimal immunogenic response to
      the agents.

PMID- 12204685
TI  - Molecular interactions in biofilms.
AB  - A biofilm may be defined as a microbially derived, sessile community
      characterized by cells that attach to an interface, embed in a matrix of
      exopolysaccharide, and demonstrate an altered phenotype. This review covers the
      current understanding of the nature of biofilms and the impact that molecular
      interactions may have on biofilm development and phenotype using the motile gram
      negative rod Pseudomonas aeruginosa and the nonmotile gram-positive cocci
      Staphylococcus aureus as examples.

PMID- 12204686
TI  - Antibiofilm approaches: prevention of catheter colonization.
AB  - Bacteria frequently attach to medical devices such as intravascular catheters by
      forming sessile multicellular communities known as biofilms, which can be the
      source of persistent infections that are recalcitrant to systemic antibiotic
      therapy. As a result of this persistence, a number of technologies have been
      developed to prevent catheter-associated biofilm formation. Whereas the most
      straightforward approaches focus on impregnating catheter material with classical
      antimicrobial agents, these approaches are not universally effective, thereby
      underscoring the need for more potent and more sophisticated approaches to the
      prevention of catheter-related biofilm infections.

PMID- 12204687
TI  - Interference with heme binding to histidine-rich protein-2 as an antimalarial
      strategy.
AB  - The erythrocytic growth stage of Plasmodium falciparum involves hemoglobin
      proteolysis as the primary nutrient source with the concomitant release of free
      heme. The liberated heme is processed by the parasite into hemozoin, a polymeric
      porphyrin dimer. Histidine-rich protein binds heme and mediates the formation of
      hemozoin, which is inhibited by the antimalarial drug chloroquine. Interference
      with heme binding was determined using a microtiterplate assay. Combinatorial
      libraries were screened and tested against parasite growth, revealing a good
      correlation between heme binding interference and the inhibition of parasite
      growth. Several of these compounds retain their potency against a chloroquine
      resistant strain of Plasmodium falciparum. The most potent compounds have IC(50)
      values less than or equal to 50 nM against chloroquine-resistant and chloroquine
      sensitive parasites.

PMID- 12204688
TI  - A quick diversity-oriented amide-forming reaction to optimize P-subsite residues
      of HIV protease inhibitors.
AB  - We report a new simple method that allows rapid preparation in solution of a
      library of compounds for in situ high-throughput screening to identify new
      inhibitors of HIV-1 protease. The method is based on the amide-forming reaction
      of a C(2)-symmetrical diamino diol core with various carboxylic acids, followed
      by a direct assay of the inhibition activity without product isolation. Sixty-two
      compounds were made and screened in less than 1 hr. The utility of this method is
      demonstrated by the identification of new P3-P3' residues that convert a
      transition state analog core from a poor binding molecule (1, K(i) > 2 microM) to
      a potent inhibitor (AB1, K(i) = 2 nM) against the wild-type, and the inhibition
      activities against resistant mutants are better than those of two existing drugs.
      This method reduces the time required for synthesis and testing of a large number
      of characterized inhibitors and should find useful applications in other enzyme
      systems.

PMID- 12204689
TI  - Functional analysis of the lipoglycodepsipeptide antibiotic ramoplanin.
AB  - The peptide antibiotic ramoplanin is highly effective against several drug
      resistant gram-positive bacteria, including vancomycin-resistant Enterococcus
      faecium (VRE) and methicillin-resistant Staphylococcus aureus (MRSA), two
      important opportunistic human pathogens. Ramoplanin inhibits bacterial
      peptidoglycan (PG) biosynthesis by binding to Lipid intermediates I and II at a
      location different than the N-acyl-D-Ala-D-Ala dipeptide site targeted by
      vancomycin. Lipid I/II capture physically occludes these substrates from proper
      utilization by the late-stage PG biosynthesis enzymes MurG and the
      transglycosylases. Key structural features of ramoplanin responsible for
      antibiotic activity and PG molecular recognition have been discovered by
      antibiotic semisynthetic modification in conjunction with NMR analyses. These
      results help define a minimalist ramoplanin pharmacophore and introduce the
      possibility of generating ramoplanin-derived peptide or peptidomimetic
      antibiotics for use against VRE, MRSA, and related pathogens.

PMID- 12204690
TI  - Controlling protein activity with ligand-regulated RNA aptamers.
AB  - Controlling the activity of a protein is necessary for defining its function in
      vivo. RNA aptamers are capable of inhibiting proteins with high affinity and
      specificity, but this effect is not readily reversible. We describe a general
      method for discovering aptamers that bind and inhibit their target protein, but
      addition of a specific small molecule disrupts the protein-RNA complex. A SELEX
      protocol was used to raise RNA aptamers to the DNA repair enzyme,
      formamidopyrimidine glycosylase (Fpg), and neomycin was employed in each round to
      dissociate Fpg-bound RNAs. We identified an RNA molecule able to completely
      inhibit Fpg at 100 nM concentration. Importantly, Fpg activity is recovered by
      the addition of neomycin. We envision these ligand-regulated aptamers (LIRAs) as
      valuable tools in the study of biological phenomena in which the timing of
      molecular events is critical.

PMID- 12204691
TI  - Structure-activity analysis of the purine binding site of human liver glycogen
      phosphorylase.
AB  - Human liver glycogen phosphorylase (HLGP) catalyzes the breakdown of glycogen to
      maintain serum glucose levels and is a therapeutic target for diabetes. HLGP is
      regulated by multiple interacting allosteric sites, each of which is a potential
      drug binding site. We used surface plasmon resonance (SPR) to screen for
      compounds that bind to the purine allosteric inhibitor site. We determined the
      affinities of a series of compounds and solved the crystal structures of three
      representative ligands with K(D) values from 17-550 microM. The crystal
      structures reveal that the affinities are partly determined by ligand-specific
      water-mediated hydrogen bonds and side chain movements. These effects could not
      be predicted; both crystallographic and SPR studies were required to understand
      the important features of binding and together provide a basis for the design of
      new allosteric inhibitors targeting this site.

PMID- 12204692
TI  - Targeting DNA bulged microenvironments with synthetic agents: lessons from a
      natural product.
AB  - Bulged regions of nucleic acids are important structural motifs whose function
      has been linked to a number of key nuclear processes. Additionally, bulged
      intermediates have been implicated in the etiology of several genetic diseases
      and as targets for viral regulation. Despite these obvious ramifications, few
      molecules are capable of selective binding to bulged sequences. Prompted by the
      remarkable affinity of a natural product metabolite, we have designed and
      prepared a series of readily accessible synthetic agents with selective bulge
      binding activity. Furthermore, by screening a library of bulge-containing
      oligodeoxynucelotides, correlations between structure and affinity of the agents
      can be drawn. In addition to potential applications in molecular biology, the
      availability of these spirocyclic agents now opens the door for rational drug
      design.

PMID- 12204693
TI  - Directed evolution of high-affinity antibody mimics using mRNA display.
AB  - We constructed a library of >10(12) unique, covalently coupled mRNA-protein
      molecules by randomizing three exposed loops of an immunoglobulin-like protein,
      the tenth fibronectin type III domain (10Fn3). The antibody mimics that bound TNF
      alpha were isolated from the library using mRNA display. Ten rounds of selection
      produced 10Fn3 variants that bound TNF-alpha with dissociation constants (K(d))
      between 1 and 24 nM. After affinity maturation, the lowest K(d) measured was 20
      pM. Selected antibody mimics were shown to capture TNF-alpha when immobilized in
      a protein microarray. 10Fn3-based scaffold libraries and mRNA-display allow the
      isolation of high-affinity, specific antigen binding proteins; potential
      applications of such binding proteins include diagnostic protein microarrays and
      protein therapeutics.

PMID- 12204694
TI  - Cellular import mediated by nuclear localization signal Peptide sequences.
AB  - The cellular delivery of therapeutic agents and their localization within cells
      is currently a great challenge in medicinal chemistry. A few cationic peptides
      have shown a strong propensity to cross the cytoplasmic membrane and enter cells.
      Nuclear localization signal (NLS) sequences are a class of highly cationic
      peptides that may be exploited for cellular import of linked cargo. A series of
      NLS sequence peptides were investigated for entry into different cancer cell
      lines by flow cytometry and confocal microscopy. All NLS peptides demonstrated
      rapid accumulation within cells when added to the cellular media. Covalent
      adducts of proteins and oligonucleotides with NLS peptides were also effectively
      imported within cells. An understanding of the structural and mechanistic
      properties of these sequences will provide great potential for the rational
      design of efficient and selective peptidic delivery systems.

PMID- 12204696
TI  - Changing paradigms in the medical treatment of glaucoma.
AB  - Glaucoma is defined by a typical optic neuropathy accompanied by characteristic
      visual field loss and eventual blindness. The major risk factor for glaucoma is
      elevated intraocular pressure (IOP). Lowering IOP is currently the only proven
      method for reducing the risk of glaucomatous visual field loss and remains the
      primary goal of therapy. With the recent introduction of many new medications
      that lower IOP, the definition of what constitutes maximum tolerated medical
      therapy has been changing. The treatment can now be tailored better to each
      individual patient. The regimen needs to be affordable, easy to understand, and
      least interfering with the patient's quality of life. beta-blockers still are the
      mainstay of initial therapy, but more and more prostaglandin analogs and also
      alpha-2 agonists are being used initially. Systemic carbonic anhydrase inhibitors
      and cholinergics are being used less frequently.

PMID- 12204697
TI  - Ocular and systemic pharmacokinetics of latanoprost in humans.
AB  - The ocular pharmacokinetics of latanoprost (13,14-dihydro-17-phenyl-18, 19,20
      trinor-PGF(2alpha)-isopropyl ester; Xalatan [Pharmacia-Upjohn, Peapack, NJ]) was
      studied in patients undergoing cataract surgery using radio-immunoassay, and the
      systemic pharmacokinetics of latanoprost was studied in healthy human volunteers
      with 3H-latanoprost as well as radioimmunoassay. After topical application,
      latanoprost was rapidly hydrolysed in the cornea and blood. The maximum
      concentration of the active drug, latanoprost acid, was detected in the aqueous
      humor 1-2 hours after topical administration of the clinical dose and amounted to
      15-30 ng/ml. The half-life of latanoprost acid in the aqueous humor was 2-3
      hours. In the systemic circulation the peak concentration of latanoprost acid
      appeared 5 minutes after topical application and reached a level of 53 pg/ml with
      an elimination half-life of 17 minutes. In patients that had been on the drug
      continuously for more than 1 year, 5 out of 10 had plasma levels of latanoprost
      acid below the limit of detection (<30 pg/ml). The mean plasma clearance was 0.40
      +/- 0.04 l/h. kg, and the volume of distribution was 0.16 +/- 0.02 l/kg after
      intravenous administration. The corresponding figures after ocular administration
      were 0.88 l/h. kg, and 0.36 l/kg. The majority of the radioactivity was recovered
      in urine (88%) and the rest was found in feces. In the eye the main metabolism of
      latanoprost was the ester hydrolysis. The only prominent chromatographic peak in
      plasma corresponded to latanoprost acid. In urine no latanoprost or latanoprost
      acid was detected. Before excretion latanoprost acid was beta oxidized to 1,2
      dinor and 1,2,3,4-tetranor latanoprost acid. These metabolites accounted for
      approximately 66% of the radioactivity in urine. In conclusion, latanoprost is
      rapidly hydrolyzed in the eye and blood to latanoprost acid. Minimal further
      metabolism occurs in the eye, but latanoprost acid undergoes beta oxidation and
      other metabolism outside the eye. After topical application the peak
      concentration in aqueous humor was approximately 10(-7) M, whereas that in plasma
      was about 10(-10) M or less.

PMID- 12204698
TI  - Identification and characterization of the ocular hypotensive efficacy of
      travoprost, a potent and selective FP prostaglandin receptor agonist, and AL
      6598, a DP prostaglandin receptor agonist.
AB  - The structure-activity studies that led to the identification of travoprost, a
      highly selective and potent FP prostaglandin analog, and AL-6598, a DP
      prostaglandin analog, are detailed. In both series, the 1-alcohol analogs are
      very effective and are thought to be acting as prodrugs for the biologically
      active carboxylic acids. The efficacy of amide prodrugs depends on the degree of
      substitution and the size of the substituents. Selected compounds are profiled in
      vitro and in vivo preclinically. Clinical studies show that travoprost 0.004%
      (isopropyl ester) provided intraocular pressure control superior to timolol 0.5%
      when used as monotherapy in patients with open-angle glaucoma or ocular
      hypertension. In clinical studies, AL-6598 0.01% provided a sustained intraocular
      pressure reduction with q.d. application; b.i.d. provided greater intraocular
      pressure control. The acute and, apparently, conjunctival hyperemia associated
      with topical ocular AL-6598 can be attenuated while maintaining intraocular
      pressure-lowering efficacy by formulating with brimonidine.

PMID- 12204699
TI  - The hydrolysis of bimatoprost in corneal tissue generates a potent prostanoid FP
      receptor agonist.
AB  - Using human and bovine corneal tissue, we investigated the in vitro metabolism of
      bimatoprost (17-phenyl-18,19,20-trinor-prostaglandin F(2alpha) ethyl amide,
      Lumigan (Allergan, Inc, Irvine, CA). Enzymatic amidase activity, which converts
      bimatoprost to the corresponding prostaglandin carboxylic acid, was found to be
      present in corneal tissue from both species. Using HPLC and mass spectrometry for
      analyses, conversion of bimatoprost to 17-phenyl-18,19,20-trinor prostaglandin
      F(2alpha) continued for at least 24 hours after excision of the cornea, with a
      conversion rate of approximately 25 microg/24 hours. This hydrolysis product is
      identical to the free acid of latanoprost with the exception of a double, rather
      than a single, bond at the carbon 13-14 position. Assuming that this conversion
      also occurs in vivo at a similar rate, this hydrolysis product may account for
      the reduction of intraocular pressure occurring in patients treated with
      bimatoprost.

PMID- 12204700
TI  - Drug delivery to the posterior segment from drops.
AB  - The published evidence that instilled drugs can affect the blood supply to the
      retina and optic nerve head in humans is examined. As a background, seven
      techniques that have been used to measure flow are briefly described and
      criticized. For timolol, the corresponding measurements, obtained by a number of
      investigators are evaluated. The outcome is very erratic and does not allow any
      conclusion as to the effect of this drug on flow. Consideration is then given to
      the possible mechanism whereby a drug could affect blood flow; directly, by
      diffusion to receptors on the vessels, or indirectly, through more anterior
      receptors. The question is raised whether the small changes in circulation
      induced by drugs would not be swamped by those resulting from natural alterations
      in the ambient light level. The literature was analyzed in the hope of
      identifying discrete entry pathways, for example, through the lens or the
      suprachoroidal space, that are sufficiently permeable to allow a significant
      quantity of drug to pass. There was an indication that a drug might diffuse
      through the lens cortex in sufficient quantity to cause a measurable rise in its
      concentration in the vitreous. In general, however, there was insufficient
      quantitative data to allow any meaningful predictions to be made. Stimulated by
      recent evidence, it is suggested that drug penetration from the tear fluid takes
      place by direct diffusion across the conjunctiva into the sclera and orbit when
      the head is supine.

PMID- 12204701
TI  - Effects of prostaglandins on the aqueous humor outflow pathways.
AB  - Topical treatments with certain prostaglandins (PGs), including FP receptor
      agonists, lower intraocular pressure by increasing uveoscleral outflow. Although
      the precise mechanism for the increased uveoscleral outflow is not known, there
      appears to be activation of a molecular transduction cascade and an increase in
      the biosynthesis of certain metalloproteinases. This leads to reduction of
      extracellular matrix components within the ciliary muscle, iris root, and sclera.
      It is possible that this reduction of extracellular matrix present within
      portions of the uveoscleral pathway may contribute to the mechanism of increased
      uveoscleral outflow. Additional mechanisms that may contribute to the PG-mediated
      increase of uveoscleral outflow include relaxation of the ciliary muscle, cell
      shape changes, cytoskeletal alteration, or compaction of the extracellular matrix
      within the tissues of the uveoscleral outflow pathway. Future studies should
      clarify the importance of these various responses that may contribute to
      increased uveoscleral outflow. At present, there is no compelling evidence for a
      substantial facility-increasing effect on the trabecular meshwork outflow for any
      of these compounds.

PMID- 12204702
TI  - The effect of latanoprost on intraocular pressure during 2 years of treatment.
AB  - Our objective was to study the intraocular pressure (IOP) in open-angle glaucoma
      or ocular hypertensive patients during long-term treatment with latanoprost. A
      total of 532 patients treated with 0.005% latanoprost were enrolled, including
      493 and 113 patients treated for 6 and 24 months, respectively. Mean IOP was
      analyzed with the analysis of variance technique. The risk of treatment failure
      was analyzed with survival analysis technique. After 2 weeks of latanoprost
      treatment, the mean IOP was reduced 8.2 (32%) and 8.9 (34%) mm Hg in the
      subgroups of patients treated for 6 and 24 months, respectively. The change in
      mean IOP during 2 years of latanoprost treatment was not statistically
      significant (p = 0.15). Patients with primary open-angle glaucoma or ocular
      hypertension showed an 86% and 97% chance of receiving a sufficient IOP reduction
      with latanoprost (p < 0.01), repectively. The initial mean IOP reduction was
      maintained throughout the 2 years of treatment.

PMID- 12204703
TI  - The effect of latanoprost compared with timolol in African-American, Asian,
      Caucasian, and Mexican open-angle glaucoma or ocular hypertensive patients.
AB  - OBJECTIVE: To study the intraocular pressure (IOP) reduction of latanoprost or
      timolol in a heterogeneous global population. METHODS: A total of 1,389 glaucoma
      or ocular hypertensive patients treated with 0.005% latanoprost once daily (n =
      737) or 0.5% timolol twice daily (n = 652) from eight clinical trials were
      included. After 3-6 months of treatment, the IOP was analyzed with use of
      analysis of covariance. RESULTS: Latanoprost or timolol gave statistically
      significant mean diurnal IOP reduction in the African-American, Asian, Caucasian,
      and Mexican patients, latanoprost with 7.9 mm Hg and timolol with 6.4 mm Hg. The
      Asian and Mexican patients showed a larger difference in mean diurnal IOP
      reduction with use of the two drugs (range 1.8-3.1 mm Hg) than the European and
      U.S. patients (range 0.6-1.7 mm Hg, p = 0.030). Latanoprost produced similar mean
      diurnal IOP reduction in patients with and without previous glaucoma treatment
      other than prostaglandins. CONCLUSION: Latanoprost or timolol statistically
      significantly reduced the mean diurnal IOP in a heterogenous global population in
      eight clinical trials. The degree of reduction appeared to be clinically useful.
      The greatest difference in the mean diurnal IOP-lowering effect of latanoprost or
      timolol was observed in Mexican and Asian clinical trials.

PMID- 12204704
TI  - The effect of latanoprost on circadian intraocular pressure.
AB  - The presence of a circadian variation of both intraocular pressure (IOP) and
      aqueous humor flow has been demonstrated in several studies. It must therefore be
      considered important to monitor IOP and evaluate the efficacy of ocular
      hypotensive drugs over the 24 hours of the day. The efficacy of latanoprost on
      IOP during both day and night has been evaluated and the most important results
      from four such studies are reviewed. The studies reviewed here clearly
      demonstrate that topical administration of latanoprost 0.005% once daily provided
      a steady reduction of the IOP during both day and night. Given as a single dose
      to healthy volunteers, latanoprost resulted in a sustained effect with a
      significant IOP reduction over 24 hours, and the reduction was still present,
      however less pronounced, even after 48 hours. Latanoprost administered once daily
      for 4 weeks to patients with glaucoma or ocular hypertension was more effective
      in reducing the IOP over 24 hours than timolol gel solution 0.5% once daily,
      timolol aqueous solution 0.5% twice daily, or dorzolamide 2% three times daily.
      Latanoprost applied once daily thus provided a better effect on the IOP together
      with a stable and sustained IOP reduction during both day and night.

PMID- 12204705
TI  - Current status of prostaglandin therapy: latanoprost and unoprostone.
AB  - Latanoprost, a prostaglandin F(2alpha) analog prodrug, and unoprostone, an analog
      of a prostaglandin metabolite, have been shown to be effective in decreasing
      intraocular pressure when used alone or in combination with other ocular
      hypotensive agents. The increase in the uveoscleral outflow and some of the side
      effects are probably FP-receptor mediated, which may account for some differences
      between the cited drugs. This article reviews the recent literature available on
      the clinical efficacy of these prostanoids, as well as the studies directly
      comparing these drugs.

PMID- 12204707
TI  - Medical treatment of normal tension glaucoma.
AB  - Normal-tension glaucoma was previously thought to be pressure insensitive, as
      medical treatment hardly reduced intraocular pressure and it did not prevent
      visual field loss. In the last decade, however, evidence has shown that the
      treatment of normal-tension glaucoma by lowering intraocular pressure can slow
      the deterioration of visual fields, hence the glaucomatous process. It was shown
      that a reduction of IOP of at least 30% is needed to induce a favorable
      alteration in the course of normal-tension glaucoma. New agents, such as
      prostaglandin analogs, the alpha(2)-adrenoceptor agonist brimonidine, and
      carbonic anhydrase inhibitors, have become available and may be of use in the
      treatment of normal-tension glaucoma. Monotherapy with prostaglandin analogs may
      meet the target of a reduction of IOP with 30%, but combination therapy will be
      needed in many cases. Few studies have been performed with brimonidine,
      travoprost, and bimatoprost, and it is suggested that more attention should be
      given to studies with these agents, as about 30% of patients with open angles and
      glaucomatous visual field defects have normal-tension glaucoma. Although
      neuroprotection is the goal of the future, no hard data are available yet which
      demonstrate that treatment with these agents will indeed result in preservation
      of visual fields.

PMID- 12204706
TI  - Bimatoprost and travoprost: a review of recent studies of two new glaucoma drugs.
AB  - Bimatoprost (Lumigan [Allergan, Inc, Irvine CA]) and travoprost (Travatan [Alcon,
      Ft Worth, TX]) are two new intraocular pressure (IOP)-lowering drugs for use in
      patients with glaucoma and ocular hypertension. This review evaluates recent
      studies comparing these new drugs with timolol and with latanoprost. In each
      study, the statistical analyses support the conclusion that these agents were
      more effective than timolol and as effective as latanoprost in terms of their
      ability to reduce IOP. The side effect profiles for bimatoprost, latanoprost, and
      travoprost were similar, but with statistically higher occurrences of hyperemia
      and eyelash growth for bimatoprost or travoprost versus latanoprost or timolol.

PMID- 12204708
TI  - Efficacy of latanoprost in reducing intraocular pressure in patients with primary
      angle-closure glaucoma.
AB  - Two independent, prospective trials were recently conducted to assess the
      efficacy of latanoprost in reducing intraocular pressure (IOP) in patients with
      primary angle-closure glaucoma (PACG). The first study was a 2-week, randomized,
      double-masked comparison of latanoprost treatment and timolol treatment in
      patients with PACG. Patients were randomized to one of two parallel treatment
      groups, receiving either placebo in the morning and latanoprost 0.005% in the
      evening, or timolol 0.5% twice daily. The mean IOP reduction in latanoprost group
      was 8.8 +/- 1.1 mm Hg (mean +/- SEM, p < 0.001; 34.2%) from a mean baseline IOP
      of 25.7 +/- 0.9 mm Hg, and the corresponding figures for the timolol group were
      5.7 +/- 0.9 mm Hg (p < 0.001; 22.6%) from a mean baseline IOP of 25.2 +/- 1.1 mm
      Hg. A significantly greater IOP reduction of 3.1 +/- 1.5 mm Hg (95% confidence
      interval: 0.1 to 6.0) was achieved in the latanoprost group compared to the
      timolol treatment group (p = 0.04). In the second study, latanoprost 0.005% once
      a day was added adjunctively to PACG patients with persistently elevated IOP
      after iridectomy, despite treatment with beta-blockers and pilocarpine. The IOP
      decreased by about 21% during the first 3 months, and showed a reduction of about
      36% at the end of 1 year. At the 1-year follow-up, IOP was <20 mm Hg in all eyes.
      In both studies, latanoprost was well tolerated with few adverse events. These
      results demonstrate that latanoprost is effective in reducing IOP in patients
      with PACG.

PMID- 12204709
TI  - Latanoprost for the treatment of pediatric glaucoma.
AB  - Latanoprost is a prostaglandin F(2alpha) analog that reduces intraocular pressure
      (IOP) by 20-40% in adults with open-angle glaucoma or ocular hypertension. The
      efficacy and safety of latanoprost in children has not been widely reported, but
      there are at least three peer-reviewed publications involving the use of this
      drug in the treatment of pediatric patients with glaucoma. Most of the patients
      in these studies showed disappointingly little IOP effect from this drug, but
      some children, particularly older children and those with juvenile-onset open
      angle glaucoma, do have a significant ocular hypotensive effect with latanoprost.
      Systemic and ocular side effects in children on latanoprost are infrequent and
      mild.

PMID- 12204710
TI  - The efficacy and safety of unfixed and fixed combinations of latanoprost and
      other antiglaucoma medications.
AB  - Adjunctive therapy for the management of glaucoma is commonly used. Unfixed
      combinations of the prostaglandin analog latanoprost and other glaucoma
      medications have been demonstrated to effectively lower intraocular pressure
      (IOP). The range of reported additional reductions in IOP compared to a
      monotherapy baseline are as follows: latanoprost-timolol (13-37%), latanoprost
      pilocarpine 2% (7-14%), latanoprost and carbonic anhydrase inhibitors (15-24.1%),
      and latanoprost and dipivefrin (15-28%). There is a fixed combination of
      latanoprost (0.005%) and timolol (0.5%) that has been investigated in Phase III
      trials in Europe and the United States. In these trials, it was noted that the
      efficacy of the fixed combination was superior to either of the monotherapy
      components. After 12 months of follow-up of patients on fixed combination, there
      was no evidence of long-term drift. The new formulation appears to be safe and
      does not demonstrate any more side effects than either of the components. The
      convenience of a fixed combination may enhance patient compliance. Unfixed
      combination therapy with latanoprost and other antiglaucoma medications and the
      fixed combination formulation of latanoprost and timolol provide an effective and
      safe option for lowering IOP in glaucoma patients.

PMID- 12204711
TI  - Latanoprost and cholinergic agonists in combination.
AB  - Latanoprost, a prodrug of a prostaglandin F(2alpha) analog, is a potent ocular
      hypotensive agent, reducing intraocular pressure (IOP) primarily by increasing
      aqueous humor drainage through the uveoscleral outflow pathway. Initial
      assessments in animals found that high concentrations of cholinergic agonists
      reduced drainage through this pathway and attenuated the effects of a PGF(2alpha)
      analog. This raised the question of whether latanoprost would be effective when
      added to the treatment regimen of patients on pilocarpine or strong miotics. In
      published clinical studies, latanoprost was additive to the maximally tolerated
      medical therapy (which included cholinergic agonists) of glaucoma patients.
      Multiple doses of physostigmine in healthy volunteers did not block the effect of
      a single drop of latanoprost during a 1-day study. One study attempting to find
      the optimal timing of administration of latanoprost and pilocarpine claimed to
      show that additivity was best when pilocarpine was given one hour after
      latanoprost in the evening. Two other studies found that the timing of the doses
      was not important. To explain the additivity of latanoprost and pilocarpine,
      aqueous humor dynamics were assessed in ocular hypertensive patients treated for
      1 week with each drug alone and then for one week in combination. The results
      showed that latanoprost increased uveoscleral outflow, pilocarpine increased
      outflow facility, and pilocarpine did not block or attenuate the uveoscleral
      outflow effect of latanoprost. The result was greater IOP reduction when these
      drugs were used in combination than when either drug was used alone. All
      available evidence demonstrates that addition of latanoprost to the treatment
      regime of patients already taking cholinergic agonists is an effective, although
      not necessarily the preferred, combination of medications for the treatment of
      elevated IOP.

PMID- 12204712
TI  - Latanoprost versus combined timolol and dorzolamide.
AB  - We reviewed available data comparing latanoprost and combined timolol and
      dorzolamide and the additive effect of latanoprost in patients receiving timolol
      and dorzolamide in combination using a literature search through the electronic
      Medline database and presentations from proceedings of recent glaucoma meetings.
      Several studies have shown that the intraocular pressure (IOP)-lowering effect of
      latanoprost once a day is equivalent to timolol 0.5% twice a day and concomitant
      or combined dorzolamide 2% twice a day. Adding latanoprost to timolol and
      dorzolamide leads to a further 16% reduction of IOP. We conclude that the effect
      on IOP reduction of latanoprost is similar to combined timolol and dorzolamide,
      and the additive effect of latanoprost to a combination of timolol and
      dorzolamide is clinically relevant. In most cases, the overall safety profile of
      latanoprost is better than combined timolol and dorzolamide.

PMID- 12204713
TI  - Combined therapy of pilocarpine or latanoprost with timolol versus latanoprost
      monotherapy.
AB  - Adjunctive intraocular pressure (IOP)-lowering therapy is widely used today, as
      one-third of all patients being treated for glaucoma need additional therapy to
      reach and maintain healthy IOPs. Timolol, latanoprost, and pilocarpine are three
      potent drugs that have been used in combination to reduce IOP. Timolol reduces
      the production rate of aqueous humor to achieve the IOP decrease. Latanoprost and
      pilocarpine both affect aqueous outflow, although by different mechanisms. The
      IOP efficacy of combined therapy with timolol and pilocarpine compared with
      timolol and latanoprost or with latanoprost alone has been investigated in three
      multicenter, randomized, clinical trials in Europe. This is a review of those
      published trials. In 2 of the 3 studies, the additional IOP lowering effect of
      latanoprost 0.005% administered once daily was compared with pilocarpine 2%
      administered 3 times daily in patients with primary open-angle glaucoma (POAG) or
      ocular hypertension currently on monotherapy with timolol 0.5% twice daily. These
      6-month studies found that the timolol and latanoprost combination reduced IOP
      more and was better tolerated with fewer side-effects than the timolol and
      pilocarpine combination. At 6 months, there was no evidence of long-term drift in
      IOP with timolol and latanoprost. This combined therapy provides an effective and
      safe option for lowering IOP in glaucoma patients. These results suggest that the
      timolol/latanoprost combination is preferable to the timolol/pilocarpine
      combination not only with regard to side effects but also to the magnitude of IOP
      reduction. Two of the 3 studies compared latanoprost monotherapy with timolol and
      pilocarpine combined therapy in patients with POAG, various other glaucomas, or
      ocular hypertension. Treatment was for 6 weeks or 6 months. In both studies,
      latanoprost was more effective and better tolerated than the combination of
      timolol and pilocarpine. These results suggest that latanoprost alone should be
      tried before the addition of pilocarpine to timolol therapy is considered. The
      convenience of daily administration of a single drop of latanoprost versus
      multiple drops of timolol and pilocarpine should improve patient compliance.

PMID- 12204714
TI  - Mechanism and clinical significance of prostaglandin-induced iris pigmentation.
AB  - The new glaucoma drugs latanoprost, isopropyl unoprostone, travoprost, and
      bimatoprost cause increased pigmentation of the iris in some patients. The
      purpose of the present article is to survey the available preclinical and
      clinical data on prostaglandin-induced iris pigmentation and to assess the
      phenomenon from a clinical perspective. Most of the data have been obtained with
      latanoprost, and it appears that there is a predisposition to latanoprost-induced
      iris pigmentation in individuals with hazel or heterochromic eye color. As
      latanoprost and travoprost are selective agonists for the prostaglandin F(2alpha)
      receptor, it is likely that the phenomenon is mediated by this receptor. Several
      studies indicate that latanoprost stimulates melanogenesis in iridial
      melanocytes, and transcription of the tyrosinase gene is upregulated. The safety
      aspects of latanoprost-induced iris pigmentation have been addressed in
      histopathologic studies, and no evidence of harmful consequences of the side
      effect has been found. Although a final assessment of the clinical significance
      of prostaglandin-induced iris pigmentation currently is impossible to make, it
      appears that the only clear-cut disadvantage is a potential heterochromia between
      the eyes in unilaterally treated patients because the heterochromia is likely to
      be permanent, or very slowly reversible.

PMID- 12204715
TI  - Histology and fine structure of the iris and outflow system following latanoprost
      therapy.
AB  - Latanoprost therapy can lead to iris darkening in susceptible individuals,
      particularly those with hazel eyes. Concerns have been raised about whether
      latanoprost, and for that matter other prostanoids, may have a harmful effect on
      the iris. In addition, it is unknown whether latanoprost causes increased
      pigmentation of the outflow pathways that might eventually lead to blockage and a
      type of pigmentary glaucoma. The present study summarizes findings from the
      authors' own laboratories on the effects of latanoprost as seen by light and
      electron microscopy of the iris and outflow tissues and reviews the as yet
      limited, relevant literature. The findings support the proposal that latanoprost
      induced eye color change is likely to be due to an increased amount of melanin
      within iris stromal melanocytes rather than any increase in melanocyte numbers,
      although many aspects of the darkening process remain obscure. No marked
      pathological changes were found in the latanoprost-treated iris; however, the
      numbers of specimens examined by us to date are still small (40 specimens in all)
      and those with latanoprost-induced darkening are even fewer (18). In the authors'
      experience, pigmentation of the outflow system in latanoprost-treated eyes was no
      greater than in eyes with primary open-angle glaucoma without prostanoid
      treatment, but there have been only limited numbers of trabeculectomy specimens
      examined. Concerns about latanoprost producing meshwork hyperpigmentation and
      pigmentary glaucoma are discussed.

PMID- 12204716
TI  - Prostaglandin-induced hair growth.
AB  - Latanoprost, used clinically in the treatment of glaucoma, induces growth of
      lashes and ancillary hairs around the eyelids. Manifestations include greater
      thickness and length of lashes, additional lash rows, conversion of vellus to
      terminal hairs in canthal areas as well as in regions adjacent to lash rows. In
      conjunction with increased growth, increased pigmentation occurs. Vellus hairs of
      the lower eyelids also undergo increased growth and pigmentation. Brief
      latanoprost therapy for 2-17 days (3-25.5 microg total dosage) induced findings
      comparable to chronic therapy in five patients. Latanoprost reversed alopecia of
      the eyelashes in one patient. Laboratory experiments with latanoprost have
      demonstrated stimulation of hair growth in mice and in the balding scalp of the
      stumptailed macaque, a primate that demonstrates androgenetic alopecia. The
      increased number of visible lashes is consistent with the ability of latanoprost
      to induce anagen (the growth phase) in telogen (resting) follicles while inducing
      hypertrophic changes in the involved follicles. The increased length of lashes is
      consistent with the ability of latanoprost to prolong the anagen phase of the
      hair cycle. Correlation with laboratory studies suggests that initiation and
      completion of latanoprost hair growth effects occur very early in anagen and the
      likely target is the dermal papilla.

PMID- 12204717
TI  - Prostaglandins and cystoid macular edema.
AB  - This review discusses the roles and interactions of prostaglandins and other
      possible chemical mediators in cystoid macular edema. Prostaglandins have been
      studied as a potential causative factor of cystoid macular edema following
      cataract/intraocular lens surgery. The authors' hypothesis and data with regard
      to the mechanisms of postoperative cystoid macular edema and other inflammatory
      conditions are presented. The effects of nonsteroidal anti-inflammatory drugs,
      which are antagonists of prostaglandin biosynthesis, on postoperative
      inflammatory conditions including cystoid macular edema are also reviewed.
      Lastly, a mechanism for the induction of cystoid macular edema by anti-glaucoma
      eyedrops, including prostaglandin analogs is proposed. The results from two
      clinical trials recently conducted by the authors suggest that the preservative
      rather than the active ingredient is the causative factor.

PMID- 12204718
TI  - Putative side effects of prostaglandin analogs.
AB  - Anecdotal case reports describe the occurrence of cystoid macular edema, iritis,
      herpes simplex keratitis, periocular skin darkening, and headaches in patients
      treated with prostaglandin analogs for glaucoma. The purpose of this article is
      to critically analyze these anecdotal case reports in light of a few well
      controlled, randomized clinical studies to determine whether conclusions can be
      made about a causal relationship between the use of prostaglandin analogs and the
      occurrence of these side effects. None of these putative side effects has been
      proven to be causally related to latanoprost therapy using valid scientific
      methodology. These possible side effects occur rarely. Cystoid macular edema,
      iritis, and herpes simplex keratitis occur in eyes with risk factors. To
      scientifically establish a causal relationship between drug therapy and rare side
      effects, repeated rechallenging with masked controls is required. With rare
      exception, such methodology has not been used with any of these putative side
      effects. Nevertheless, even without firm establishment of a causal relationship,
      caution is advised with the use of prostaglandin analogs in eyes with risk
      factors for cystoid macular edema, iritis, and herpes simplex keratitis until
      properly designed, large, controlled studies provide more definitive information.

PMID- 12204719
TI  - Prostaglandin postscript: a personal reflection.
AB  - The long and arduous process that led to the development of ocular hypotensive
      prostaglandin derivatives over the past three decades has been reviewed several
      times. In this "postscript" to the second Survey of Ophthalmology supplement
      devoted to the ocular hypotensive effects of prostaglandin derivatives, only two
      aspects of this new approach to the medical management of glaucoma are discussed:
      1) The implication of the observed prostaglandin-induced increase in iridial
      pigmentation with respect to the understanding of the role of prostaglandins and
      of iridial melanocytes in the protection against the damaging effects of light,
      and in the maintenance of normal intraocular microenvironment; and 2) The
      rationale behind the use of a combined formulation of a prostaglandin derivative
      and a beta-blocker for the protection against increased intraocular pressure. The
      need to consider not only target pressure, but also target mechanisms, in the
      selection of medical therapy regimen for any given glaucoma patient is
      emphasized.

PMID- 12204720
TI  - Results of lung metastasectomy from breast cancer: prognostic criteria on the
      basis of 467 cases of the International Registry of Lung Metastases.
AB  - OBJECTIVE: Metastatic breast cancer is still defined as an incurable disease.
      Although the prognosis after resection of isolated metastases to the lung is much
      better than after chemotherapy most oncologists and gynecologists disapprove of
      lung metastasectomy. METHODS: In order to summarize the experience of pulmonary
      metastatic surgery and to achieve more relevant data by an increased number of
      cases, we evaluate the data of the International Registry of Lung Metastases of
      467 patients having lung metastases from breast cancer with regard to long-term
      survival and prognostic factors. RESULTS: In 84% a complete metastatic resection
      was possible. The survival rates are 38% after 5 years, 22% after 10 years, and
      20% after 15 years. Prognostic factors are a disease-free interval of > or = 36
      months with 5-year survival of 45%, a 10-year survival of 26% and a 15-year
      survival of 21% (P=0.0001), solitary lung metastasis is associated with a
      survival rate of 44% after 5 years and of 23% after 10 and 15 years, but this is
      not statistically significant compared to multiple metastases. When establishing
      prognostic groups as suggested by Pastorino and the International Registry of
      Lung Metastases based on the risk factors disease-free interval, number of
      metastases and complete resection the group with the best prognosis showed 5-year
      survival of 50%, 10- and 15-year survival of 26% with a median survival of 59
      months. CONCLUSION: Considering the low morbidity and mortality rate, we think
      that lung metastasectomy today is the best treatment option in selected cases of
      lung metastases from breast cancer.

PMID- 12204721
TI  - Massive hemoptysis: what place for medical and surgical treatment.
AB  - OBJECTIVE: The objective of the study was to define timing of surgical treatment
      in management of massive hemoptysis. METHODS: We performed a retrospective review
      of all patients admitted for massive hemoptysis in the intensive care unit of our
      thoracic surgery department. Treatment was managed according to the patient's
      status, the etiology of bleeding, the findings of bronchoscopy and computed
      tomographic scan. Therapeutic measures available were medical treatment, tracheal
      intubation (single or double lumen tube), interventional endoscopy, arterial
      embolisation and surgical treatment. RESULTS: Between September 1996 and December
      2001, 43 patients were treated (nine females and 34 males with mean age of 54
      years, range from 32 to 79). The mean red cell blood transfusion per patient was
      1.57 Units. The patients were classified into three groups: Group 1, 11 patients
      were operated on immediately close to the bleeding crise (five pneumonectomy and
      six lobectomy); Group 2, five patients for whom operation was delayed from the
      7th to the 22nd day after cessation of bleeding (five lobectomy); Group 3, 27
      patients were treated by non-surgical methods (medical treatment, endobronchial
      treatment, percutaneous embolisation). Fifteen patients underwent an arterial
      embolization, which was complete in 13 cases. Among the five patients of group 2,
      cessation of bleeding was obtained by bronchial embolisation in four cases.
      Considering the whole series, 10 (23%) patients died: three (19%) patients in
      group 1, zero in group 2, seven (26%) in group 3. In two patients who were
      suffering from tumor necrosis, hemoptysis relapsed leading to death. CONCLUSION:
      Emergency thoracotomy for massive hemoptysis is at high risk. In case of bleeding
      from the arterial bronchial vessels, embolization may enable to postpone surgery
      and operate secondarily. In case of bleeding from the pulmonary vessels (tumor
      necrosis), surgical treatment must be immediate. An algorithm for management is
      proposed.

PMID- 12204722
TI  - Benign tracheal and laryngotracheal stenosis: surgical treatment and results.
AB  - OBJECTIVES: Benign tracheal stenoses remain the most common indications for
      tracheal resection. We report lessons learned with surgical management of
      tracheal stenoses in a consecutive series of 65 patients from the beginning of
      our experience to date. METHODS: From December 1991 to January 2001 65 patients
      underwent primary tracheal and laryngotracheal resection and reconstruction for
      non-neoplastic stenoses. There were 39 males and 26 females with a median age of
      33 years (range 14-74 years). There were 58 cases of postintubation and seven of
      idiopathic stenosis. A cervical approach was used in 60 patients, and a cervical
      incision with sternal split in four and with sternotomy in one. We performed 45
      (69.2%) tracheal resections and 20 (30.8%) laryngotracheal resections. The length
      of resection ranged between 1.5 and 4 cm (median 2.5 cm). The range of resected
      rings was two to eight (median five). RESULTS: Fifty-four patients received a
      preoperative treatment. Preoperative procedures consisted of laser therapy (37),
      tracheostomy (38) and endotracheal prosthesis (16). We had major complications in
      eight patients (12.3%) and minor complications in 15 patients (23%). The most
      frequent complications were: temporary vocal cord dysfunction (eight patients),
      wound infection (five patients), anastomotic dehiscence (four patients), vocal
      cord paralysis (two patients), granulation tissue (two patients), deglutition
      dysfunction (one patient) and restenosis (one patient). Perioperative mortality
      was 1.5% (one patient). In classifying final results obtained, 54 patients
      achieved an excellent result, eight a good result and two satisfactory.
      CONCLUSIONS: The strategy for treatment of airway stenoses is now well
      established and leads to a high level of success with minimal or no sequelae.
      Meticulous preoperative assessment and preparation associated with a perfect
      surgical technique is mandatory to obtain good results. Preoperative treatments
      (laser and/or endotracheal prosthesis) could increase the extent of injury and
      the length of stenosis.

PMID- 12204723
TI  - Bullectomy is comparable to lung volume reduction in patients with end-stage
      emphysema.
AB  - OBJECTIVES: Emphysema is one of the most prevalent disabling diseases, not
      modified by current medical treatment and physical rehabilitation. Lung
      transplantation is an effective clinical option in end-stage emphysema but it is
      available only for a limited number of patients. Bullectomy and lung volume
      reduction represent other surgical options to improve symptoms and exercise
      tolerance in selected patients. Both procedures allow the removal of the area of
      emphysematous lung resulting in improvement in chest wall mechanics,
      ventilation/perfusion ratio and re-expansion and better function of the residual
      lung. There is some evidence that in patients with end-stage emphysema bullectomy
      and lung volume reduction work in the same manner and yield similar functional
      results. METHODS: We compared and analyzed retrospectively two groups of patients
      with end-stage emphysema who underwent bullectomy or lung volume reduction. Over
      the last 5 years 20 patients with end-stage emphysema presenting with bullae
      underwent thoracoscopic bullectomy (Group I). During the same period of time 18
      patients with end-stage non-bullous emphysema underwent thoracoscopic unilateral
      lung volume reduction. Pre-operative baseline respiratory function data, peri
      operative data, and functional results recorded at 6 and 12 months were compared
      and analyzed. RESULTS: Both groups were homogeneous in terms of age, degree of
      respiratory derangement and severity of emphysema. Complication rate and peri
      operative data were similar in the two groups. Improvement in symptoms,
      respiratory function and exercise tolerance was comparable. CONCLUSIONS: Our
      experience supports the hypothesis that the physiopathological basis of
      respiratory improvement after bullectomy and lung volume reduction surgery in
      patients with end-stage emphysema is the same, although the exact mechanism
      remains incompletely understood.

PMID- 12204724
TI  - Successful lung volume reduction surgery brings patients into better condition
      for later lung transplantation.
AB  - OBJECTIVES: Lung volume reduction surgery (LVRS) is accepted as a potential
      alternative therapy to lung transplantation (LTX) for selected patients. However,
      the possible impact of LVRS on a subsequent LTX has not been clearly elucidated
      so far. We therefore analyzed the course of 27 patients who underwent LVRS
      followed by LTX in our institution. METHODS: Twenty-seven patients (11 male, 16
      female, mean age 51.9+/-2.2 years) out of 119 patients who underwent LVRS between
      1994 and 1999 underwent LTX 29.7+/-3.2 months (range 2-57 months) after LVRS.
      Based on the postoperative course of FeV1 after LVRS (best value within the first
      6 months postoperatively compared with the preoperative value) patients were
      divided into two groups: Group A (n=11) without any improvement (FeV1 <20%
      increase), and Group B (n=16) with FeV1 increase > or = 20% after successful LVRS
      which declined to preoperative values after 8-42 months. Subsequent LTX was
      performed 22.9+/-5.6 months after LVRS in Group A and 34.3+/-4.9 months after
      LVRS in Group B (P<0.05). Patients were analyzed according to the course of their
      functional improvement and of their body mass index (BMI) after LVRS and to
      survival after LTX, respectively. Values are given as the mean+/-SEM and
      significance was calculated by the chi(2)-test whereas continuous values were
      estimated by Student's t-test. RESULTS: Patients in Group A without improvement
      in FeV1 after LVRS had no increase in BMI as well and this resulted in a high
      perioperative mortality of 27.3% after LTX. On the contrary, patients in Group B,
      who had a clear increase of FeV1 after LVRS, experienced a significant increase
      of BMI of 23.2+/-4.5% as well (P<0.05). This improvement in BMI remained stable
      despite a later deterioration of FeV1 prior to LTX. After LTX, these patients had
      a significantly lower perioperative mortality of 6.3% as compared to Group A
      (P=0.03). CONCLUSIONS: Successful LVRS delays the need for transplantation,
      improves nutritional status and brings patients into a better pretransplant
      condition, which results in decreased perioperative mortality at LTX. Patients
      after failed LVRS, however, should be considered as poor candidates for later
      transplantation.

PMID- 12204725
TI  - sCR1sLe(X) reduces lung allograft ischemia-reperfusion injury but does not
      ameliorate acute rejection.
AB  - BACKGROUND: Combined inhibition of complement and leukocyte adhesion by
      sCR1sLe(X) reduces lung allograft dysfunction up to 24 h. In the present study
      its effect on graft function and acute rejection was evaluated up to 5 days after
      experimental transplantation. METHODS: Orthotopic single left lung
      transplantation was performed in 35 male rats (Brown Norway to Fischer 344) after
      a total ischemic time of 20 h. Two groups were assessed after 1, 3, and 5 days
      post-transplant, respectively (n=5 per group and time point): controls vs.
      recipients which received 10 mg/kg sCR1sLe(X) 15 min prior to reperfusion. In
      addition, five animals received 10 mg/kg per day sCR1sLe(X) for 5 days. For blood
      gas analysis of the graft, the contralateral lung was occluded for 5 min to
      assess graft function. Lung grafts were flushed, and histological grading was
      performed in blinded fashion according to the International Society for Heart and
      Lung Transplantation criteria. RESULTS: Graft PaO(2) in recipients treated with
      sCR1sLe(X) was superior on day 1 (383+/-118 vs. 56+/-15 mmHg; P<0.0001) and day 3
      (446+/-48 vs. 231+/-108 mmHg; P<0.0001). Five days after transplantation, no
      difference in PaO(2) was found (61+/-28 vs. 83+/-31 mmHg; P=0.59). Repeated
      treatment with sCR1sLe(X) for 5 days did not improve PaO(2) (64+/-5 mmHg; P=0.65
      vs. control; P=0.93 vs. sCR1sLe(X)). At any time point, there was no difference
      in the degree of rejection between groups. CONCLUSIONS: In this model sCR1sLe(X)
      provided marked improvement of graft function up to 3 days, but inhibition of
      both complement system and selectin dependent leukocyte adhesion failed to
      protect against acute rejection.

PMID- 12204726
TI  - Intrapericardial fibrinolytic therapy in purulent pericarditis.
AB  - OBJECTIVE: Purulent pericarditis is a rare disease that is being conventionally
      managed with intravenous antibiotics and pericardial drainage. In our study, we
      used intrapericardial fibrinolytic treatment together with pericardiocentesis and
      antibiotic therapy. We evaluated the role of intrapericardial fibrinolytic
      treatment in nine purulent pericarditis patients. METHODS: Six children and three
      adult patients with purulent pericarditis, aged between 5 and 50 years, were
      treated with intrapericardial fibrinolysis by streptokinase. Intrapericardial
      drainage catheter was placed into the subxyphoidal localization under local
      anaesthesia and echocardiography guidance, streptokinase was infused into the
      pericardial sac as the fibrinolytic agent. RESULTS: Repeat echocardiograms showed
      no reaccumulation of pericardial effusions, pericardial thickening or
      constrictions. No patients had systemic bleeding, arrhythmias, or hypotension.
      There was one death which was due to sepsis and congestive heart failure.
      CONCLUSION: We believe that early pericardial drainage and intrapericardial
      fibrinolysis appears to be safe and effective in the treatment of purulent
      pericarditis.

PMID- 12204727
TI  - Telemedicine for cardiac surgery candidates.
AB  - BACKGROUND: Cardiac surgery is generally well or over-represented in many Western
      countries. Since the southern part of Switzerland relies on 300 km distance
      centers for cardiac surgery, we started a project of telemedicine for the distant
      evaluation of cardiac surgery candidates. We report our experience of the results
      of the diagnosis made by telemedicine and by direct scrutiny of coronary
      angiograms. METHODS: Coronary angiography was performed at the distant hospital
      by an invasive cardiology team. Teletransmission of images was performed using
      three Integrated Service Digital Network (ISDN) lines by direct transmission of
      recent recording. A total of 98 cases were reviewed (87 aorto-coronary bypass
      candidates, seven valvular and four congenital heart disease). We further
      performed a prospective blinded comparison of 47 consecutive cases with severe
      coronary artery disease (CAD) with respect to localization and number of
      significant coronary lesions, obtained by direct scrutiny of the original
      angiograms and the evaluation obtained with the teletransmitted images. RESULTS:
      In 89 cases of the 98 analyzed (91%) correct diagnosis and surgical approach
      could be established by distant transmission. In nine cases (9%, all
      aortocoronary bypass candidates) definitive diagnosis and treatment was feasible
      only by direct scrutiny of the original angiograms. Five critically ill patients
      were urgently referred to the surgical care center based on the correct distant
      diagnosis. The blinded comparison of distant diagnosis and direct scrutiny of
      angiograms in defining 1-2-3 vessel CAD was good: r=0.87, P<0.01. CONCLUSION:
      Initial experience using non-sophisticated telemedical transmission of angiograms
      of cardiac surgery candidates seems to be a promising facility for distantly
      located centers.

PMID- 12204728
TI  - Minimally invasive vein harvesting significantly reduces pain and wound
      morbidity.
AB  - OBJECTIVES: Minimally invasive saphenous vein harvesting is advocated to reduce
      wound morbidity. Our early experience with minimally invasive techniques,
      however, suggested that increased tissue traction and trauma might follow. We
      aimed to test the hypothesis that minimally invasive harvesting reduces post
      operative pain and inflammation. A secondary objective was to determine if
      minimally invasive harvesting could be performed efficiently. METHODS: Forty
      patients were prospectively randomised into minimally invasive harvesting
      (Minimal, n=22) and traditional open harvesting (Open, n=18). A modified bridging
      technique was used for minimally invasive harvesting (SaphLITE, Genzyme Surgical
      Products, Cambridge, MA, USA). One surgeon performed all operations. Primary end
      points were signs of impaired healing (a composite score) and pain (visual
      analogue score). Secondary end-points (operation variables) were also collected.
      Continuous variables were analysed by Student's t-test and categorical variables
      were analysed by Mann-Whitney U-test. RESULTS: There were no significant
      demographic differences between the two groups (height, weight, albumin,
      diabetes, and peripheral vascular disease). In the early post-operative period,
      Minimal group had significantly less leg wound pain (P=0.04) and wound sepsis
      scores (P=0.01). Sternal pain was the same in both groups. After 6 weeks, wound
      scores and leg pain scores were not significantly different. There were no
      significant differences in rate of harvest (1.1 cm/min in each group). In Minimal
      group, 4 cm veins were harvested for each 1 cm skin incision compared with 1 cm
      in Open group (P<0.01). CONCLUSIONS: Minimally invasive saphenous vein harvesting
      significantly reduces early post-operative leg pain and wound sepsis. Our study
      demonstrates that minimally invasive harvesting can be performed at a
      satisfactory speed and should be considered to help reduce early post-operative
      morbidity.

PMID- 12204729
TI  - Mechanisms and future directions for prevention of vein graft failure in coronary
      bypass surgery.
AB  - Coronary artery bypass grafting has been utilized as a beneficial treatment for
      myocardial ischemic disease for over three decades. Failure of coronary artery
      venous grafts occurs at a substantial rate and has a large impact on two main
      endpoints, survival and quality of life. An exhaustive amount of basic research
      has been generated to delineate possible mechanisms responsible for graft failure
      and modalities to prevent its occurrence. Although pharmacotherapy exists,
      insufficient translation has emerged from the bench to the operating room. In
      this article, we review the literature regarding the current mechanisms and
      mediators including growth factors, nitric oxide and genetics leading to
      saphenous vein graft occlusion. The review addresses the current state of affairs
      and modes for prevention of vein graft failure perioperatively and newer
      technologies that may help ameliorate this problem in the future.

PMID- 12204730
TI  - The effect of preoperative digitalis and atenolol combination on postoperative
      atrial fibrillation incidence.
AB  - PURPOSE: The most frequent arrhythmia after coronary artery bypass surgery is
      atrial fibrillation (AF). The prevention and treatment of this type of arrhythmia
      is subobtimal. Digitalis, beta-blockers, diltiazem and amiodarone are the
      preferred drugs for the treatment. This study was designed to compare the effects
      of preoperatively started digitalis and atenolol in combination and separately,
      on the incidence of AF that occurs within 7 days following the operation.
      MATERIALS AND METHOD: One-hundred and sixty patients who had similar demographic
      properties were randomly grouped as group I, that preoperatively received
      combined drug therapy (n=40), group II preoperatively used digitalis (n=40),
      group III atenolol (n=40), and group IV was the control group (n=40). RESULTS:
      Postoperative AF incidence was 25, 15,4, and 17,9% in groups IV, III, and II,
      respectively, whereas it was 5% in group I which was lower than all other groups,
      but the difference was only significant between groups I and IV (P=0.012).
      CONCLUSION: The combined use of atenolol and digitalis preoperatively was
      considered as an efficient treatment for lowering the incidence of AF following
      coronary artery bypass surgery.

PMID- 12204731
TI  - Warm retrograde blood cardioplegia saves more ischemic myocardium but may cause a
      functional impairment compared to cold crystalloid.
AB  - OBJECTIVES: Ongoing ischemia, or even ischemia in progress, is regularly
      encountered in today's patients amenable to cardiac surgery. We set out to assess
      the effect of 'active resuscitation' during cardioplegia with warm continuous
      retrograde blood cardioplegia (WB) in a protocol simulating a clinical situation.
      METHODS: After 60 min with a regional ischemic injury to the left ventricle, 21
      pigs were randomized to receive no treatment (control), cold retrograde
      intermittent crystalloid cardioplegia (CC) or WB. All animals were put on
      cardiopulmonary bypass. After 1h of cardioplegia and 1 h of reperfusion the
      perfused left ventricle was colored with methylene blue. After excision of the
      hearts a standard planimetri technique was used to determine the area at risk and
      amount of necrosis (triphenyltetrazolium). Heart rate, mean arterial pressure
      (MAP), cardiac output and myocardial blood flow were recorded as well as
      myocardial oxygen consumption, plasma levels of free fatty acids, glucose,
      lactate and Troponin T from the coronary sinus. RESULTS: The area at risk of the
      left ventricle was 13.6+/-1.2%. We found 71+/-2, 61+/-3 and 30+/-2% necrosis of
      the area at risk in the controls, CC and WB, respectively (P<0.001, CC versus
      control and P<0.0001, WB against CC and control). Troponin T release was highest
      in the CC group in the reperfusion period. Glucose levels increased significantly
      after ischemia in the controls and WB. In accordance with the amount of saved
      myocardium in the WB group which also had a normal coronary sinus lactate level
      as opposed to the fourfold increase in the CC group after ischemia. After
      standstill cardiac output and MAP were significantly lower than baseline values
      in the WB group only (P<0.05). CONCLUSIONS: CC did reduce the size of the
      infarction by about 10% compared to control animals, whereas WB reduced the
      infarction by more than 50% of that seen after CC. Both modalities are, however,
      associated with a functional reduction during the first 60 min of reperfusion, WB
      being the worst.

PMID- 12204732
TI  - Coronary active perfusion system can maintain myocardial blood flow and tissue
      oxygenation.
AB  - OBJECTIVES: To avoid myocardial ischemia in off-pump coronary artery bypass, we
      developed a coronary active perfusion system (CAPS). The purposes of this study
      were to investigate the changes in myocardial blood flow and tissue oxygenation
      during CAPS perfusion, and to validate the ventricular arrhythmias and
      hemodynamic deterioration preventing the effect. METHODS: Sixteen pigs were
      divided into a CAPS perfusion group (group C) and a simple coronary occlusion
      group (group O). The left anterior descending coronary artery was snared in both
      groups and 30 min of CAPS perfusion was performed in group C. RESULTS:
      Ventricular arrhythmias were not observed in group C, but occurred in seven out
      of eight pigs in group O (P=0.003). None of the hemodynamic variables changed in
      group C, but they deteriorated in group O. Myocardial blood flow, saturation, and
      hemoglobin plus myoglobin concentration were maintained with a baseline level in
      group C, but decreased significantly in group O (P<0.001). CONCLUSION: CAPS is a
      reliable method to avoid myocardial ischemia during coronary occlusion and it may
      be useful for off-pump coronary artery bypass

PMID- 12204733
TI  - Kinetics of heat shock protein 70 synthesis in the human heart after cold
      cardioplegic arrest.
AB  - OBJECTIVE: Protection of the myocardium against ischemia/reperfusion injury is a
      major challenge in cardiac surgery and cardiology. A cardioprotective role of
      heat shock proteins (Hsp), in particular Hsp 70, against ischemia has been
      demonstrated. A prerequisite for clinical exploitation of high Hsp 70 levels in
      the heart during ischemia is the determination of the efficacy and the kinetics
      of cardiac Hsp synthesis in vivo. METHODS: We examined Hsp 70 and other immediate
      early genes, that are induced by cardioplegia and reperfusion, in right atrial
      biopsies taken from 15 patients during coronary artery bypass grafting. Specimens
      were obtained before cardioplegia and after ending of reperfusion and
      subsequently studied by immunohistochemistry and Western blot analyses. RESULTS:
      Overall Hsp 70 increased 2.0+/-1.1-fold (P<0.01) in the nucleus as well as in the
      cytosol of myocytes and endothelial cells during open-heart surgery. As
      determined by comparison to a dilution series of recombinant protein, Hsp 70
      levels amounted up to 6 per thousand of total cellular protein. The increase of
      Hsp 70 correlated well with the duration of cardioplegia and reperfusion
      (P<0.005) showing a markedly accelerated increase at periods longer than 2 h.
      Further, the immediate early gene c-Fos also increased 2.4+/-2.2-fold during open
      heart surgery (P<0.05), whereas other members of the Hsp family, like Hsp 27 and
      Hsp 90, showed no significant changes in protein levels during cardioplegia and
      reperfusion. CONCLUSIONS: These findings demonstrate that protein levels of Hsp
      70 in the myocardium increase to significant amounts within few hours after
      induction. The optimum time point for induction of Hsp 70 appears to be at least
      2 h before open-heart surgery.

PMID- 12204734
TI  - Six-year prospective audit of chest reopening after cardiac arrest.
AB  - OBJECTIVE: To identify which patients benefit from chest reopening after cardiac
      arrest. SETTING: Cardio-thoracic hospital undertaking full range of adult cardio
      thoracic surgery. METHODS: In-hospital arrests were prospectively audited over a
      6-year period. Information was collected for every patient whose chest was
      reopened following cardiac arrest: location of arrest, type of arrest, specialty,
      time since surgery, time to chest reopening, location of chest opening, surgical
      findings on reopening, time to cardiopulmonary bypass (if used) and patient
      outcomes. EXCLUSIONS: Arrests in theatre and chest openings for reasons other
      than cardiac arrest. RESULTS: There were 818 confirmed in-hospital arrests
      following 'cardiac arrest calls'. Chest reopening was undertaken in 79 surgical
      patients. Overall survival to discharge was 20/79 (25%). Favourable determinants
      of outcome were: arrest on intensive care unit (ICU), arrest within 24 h of
      surgery and reopening within 10 min of arrest. Nineteen of 58 (33%) chest
      openings following arrests on the ICU survived to discharge compared to one of 21
      (5%) patients whose initial arrest was outside the ICU (P=0.017). One of nine
      ward arrests scooped to ICU for chest reopening survived whereas all 12 patients
      reopened on the ward died. Fifteen of 40 patients (38%) reopened within 24 h
      surgery survived compared to five of 39 patients where reopening was undertaken
      more than 24 h after surgery (P=0.02). Fourteen of 29 (48%) patients opened
      within 10 min of arrest survived to discharge compared to six of 50 (12%)
      patients where time to reopening was more than 10 min (P=<0.001). Seven of 22
      patients (32%) patients where emergency bypass was utilised survived to
      discharge. CONCLUSION: This study strongly confirms the benefit of chest
      reopening after cardiac arrest in the cardiac surgical ICU. Patients who arrest
      within 24 h of surgery and in whom reopening is instituted within 10 min are
      particularly likely to benefit. The value of chest reopening in arrests outside
      the ICU remains unresolved. All patients reopened on the ward died, suggesting
      that this practice should be discontinued. Early 'scoop and run' resulted in one
      solitary survivor though it should probably be restricted to patients who arrest
      within 72 h of surgery as surgically remediable problems are unlikely after this
      time.

PMID- 12204735
TI  - The beneficial effect of revascularization on jeopardized myocardium: reverse
      remodeling and improved long-term prognosis.
AB  - OBJECTIVES: To evaluate the impact of viability/ischemia before revascularization
      on improvement in systolic performance, reverse remodeling, symptoms and long
      term prognosis post-revascularization. METHODS: Fifty patients underwent thallium
      201 imaging before revascularization to assess stress-induced ischemia and
      viability ('jeopardized myocardium'). Left ventricular (LV) ejection fraction
      (EF), LV end-systolic volume index (LVESVI) and LV end-diastolic volume index
      (LVEDVI) were determined before and 3 months post-revascularization. Graft/vessel
      patency was controlled by repeat angiography. Long-term follow-up data (New York
      Heart Association (NYHA) class, hard events) were acquired up to 3 years.
      RESULTS: Patients with > or = 5 jeopardized segments on thallium-201 imaging
      demonstrated improvement of LVEF at 3 months (from 35+/-6 to 43+/-6%, P<0.001),
      with reverse remodeling (LVESVI decreased from 68+/-16 to 52+/-14 ml/m(2),
      P<0.001; LVEDVI decreased from 103+/-21 to 91+/-18 ml/m(2), P<0.001), and
      improved in NYHA class with excellent long-term prognosis (0% event rate).
      Conversely, patients with <5 jeopardized segments failed to improve in LVEF (34+/
      4 vs. 33+/-7%, NS), and exhibited ongoing remodeling (LVESVI increased from 70+/
      14 to 78+/-23 ml/m(2), P<0.001; LVEDVI increased from 106+/-19 to 116+/-25
      ml/m(2), P<0.001), without improvement in NYHA class, and worse long-term
      prognosis (29% event rate). CONCLUSION: Patients with jeopardized myocardium
      benefit from revascularization with improvement in LVEF, reverse remodeling,
      improvement in NYHA class and favorable long-term prognosis.

PMID- 12204736
TI  - Surgical treatment of complex cardiac anomalies: the 'one and one half ventricle
      repair'.
AB  - OBJECTIVE: One and one half ventricle repair is a surgical option for congenital
      cardiac anomalies characterised by right ventricle (RV) hypoplasia and/or
      dysplasia. METHODS: From March 1994 to March 2001, eight patients (mean age 9.1
      years, range 7 months to 35 years) with hypoplastic and/or dysplastic RV
      underwent correction of their intracardiac anomaly in association with a BCPS
      (one and one half ventricle repair). Preoperative diagnoses included: Ebstein's
      anomaly of tricuspid valve (TV) in two, inlet ventricular septal defect (VSD) in
      association with straddling/overriding TV in two patients, pulmonary atresia
      intact ventricular septum in one, tertralogy of Fallot in association with
      complete atrioventricular canal defect in one, truncus arteriosus in one and
      heterotaxy syndrome with VSD and anomalous systemic venous return in one. Four
      patients underwent previous surgery which included: main pulmonary artery (MPA)
      banding in two patients, pulmonary valvotomy, central shunt and right ventricular
      outflow tract reconstruction in one, pulmonary artery separation from truncus
      arteriosus and modified Blalock-Taussig shunt in one, and MPA closure in one. Two
      patients underwent a bidirectional cavo-pulmonary shunt before the one and a one
      half ventricle repair. Associated cardiac lesions were treated simultaneously.
      RESULTS: There were no hospital deaths. All the patients were discharged home in
      good clinical conditions. There were no late deaths or reoperations. At mean
      follow-up of 29.8 months (range 8 months to 7.3 years) all the patients are alive
      and in good general conditions. MPA percutaneous balloon dilation was performed
      in two patients at 33 and 4 months, respectively, both after MPA reconstruction
      (which was previously ligated) and dilation of the left pulmonary artery branch
      in one patient, repeated twice at 10 and 14 months from repair, for a hypoplastic
      left pulmonary artery after truncus arteriosus repair. CONCLUSIONS: Surgical
      treatment of congenital cardiac anomalies in the presence of a hypoplastic and or
      a dysplastic RV by means of one and one half ventricle repair has the advantage
      of reducing the surgical risk for biventricular repair, and compared to the
      Fontan circulation, it maintains a low right atrium pressure, a pulsatile
      pulmonary blood flow and improves the systemic oxygen saturation. Short and
      medium-term results are promising. Longer follow-up is needed, to prove the
      efficacy of such a repair, in the long term.

PMID- 12204737
TI  - Pitfall in coronary artery bypass surgery: poor flow of left internal mammary
      artery to left anterior descending artery graft due to compression by a chest
      drain.

PMID- 12204738
TI  - A giant sternal abscess following traumatic sternal fracture.

PMID- 12204739
TI  - Single pulmonary nodules: localization with intrathoracoscopic ultrasound -- a
      prospective study.
AB  - This prospective study, based on 13 patients with single pulmonary nodules of
      width between 10 and 30 mm, was performed to verify the utility of
      intrathoracoscopic ultrasound to localize the single pulmonary nodule. In all 13
      cases the ultrasound examination was able to localize the position of nodules,
      but the homogeneous hypoechoic pattern of nodules observed in ten of 13 cases did
      not prove whether the lesion was benign or malign. In conclusion, we can confirm
      that intrathoracoscopic ultrasound examination is a safe, risk-free and less
      expensive method of localizing the single pulmonary nodules.

PMID- 12204740
TI  - A simple distal coronary perfusion technique in off-pump coronary artery bypass.
AB  - This communication describes the surgical technique and clinical outcomes of a
      simple coronary perfusion technique for use during off-pump coronary artery
      bypass grafting. An intra-coronary shunt tube connected to the graft conduit
      (saphenous vein or radial artery) with an arterial blood source (ascending aorta
      or right internal thoracic artery) was inserted distally via a coronary
      arteriotomy for temporary perfusion of six left anterior descending arteries and
      two right coronary arteries.

PMID- 12204741
TI  - Axillary artery cannulation in surgery of the ascending aorta and the aortic
      arch.
AB  - Potential advantages of axillary artery perfusion instead of femoral perfusion
      are antegrade aortic flow with decreased risk of atheremboli, low risk of false
      lumen perfusion in aortic dissections, avoidance of groin manipulation, and a
      possibility of antegrade cerebral perfusion during cardiocirculatory arrest. In
      20 patients undergoing proximal aortic surgery, perfusion via the axillary artery
      was performed with direct cannulation or with an end-to-side anastomosed Gore-Tex
      graft. In two patients conversion to femoral artery cannulation was necessary.
      There were no axillary complications, hospital mortality was three out of 22, and
      no stroke occurred.

PMID- 12204742
TI  - Paradoxic aortic arch embolization with occlusion of the supraaortic arteries.
AB  - Pulmonary embolization usually occurs when thrombotic material that originates
      from deep venous thrombosis of the lower extremities is washed out into the
      pulmonary vasculature via the blood stream. However, in the presence of a patent
      foramen ovale (PFO), systemic paradoxic embolization may also occur (Am J Surg
      176 (1998) 158). Here, we report on the case of a patient with a PFO, who
      developed paradoxic embolization of the aortic arch following deep venous
      thrombosis and massive pulmonary embolism.

PMID- 12204743
TI  - False aneurysm of the ascending aorta concomitant with chronic mediastinitis
      after tube graft replacement in octogenarian.
AB  - An 81-year-old man developed impending rupture of a false aneurysm of the
      ascending aorta concomitant with chronic mediastinitis lasting for 10 years after
      tube graft replacement. He had undergone various infection-related mediastinal
      surgical procedures. He was successfully treated by debridement of infected
      tissues, patch repair of the false aneurysm, and transposition of the right
      latissimus dorsi muscle flap. The postoperative course was uneventful except for
      seromas. A chest computed tomographic scan performed 5 and 24 months after
      surgery showed no signs of recurrent aneurysm formation. A conservative surgical
      treatment including muscle flap transposition was effective in octogenarian.

PMID- 12204744
TI  - Pseudoaneurysm of the thoracic aorta in patients with human immunodeficiency
      virus infection.
AB  - Arterial pseudoaneurysm has been reported as a possible complication of
      immunodeficiency virus infection. We report two cases of HIV-positive patients
      with a pseudoaneurysm at the level of the descending thoracic aorta. The first
      patient refused surgery and has been followed up to 14 months, whereas the second
      patient underwent successful surgical repair. The importance of magnetic
      resonance imaging in the diagnosis of thoracic aorta pseudoaneurysm is also
      discussed.

PMID- 12204745
TI  - One-stage repair of aortic isthmus atresia, aortic arch hypoplasia and ascending
      aorta aneurysm via midline sternotomy and normothermic perfusion.
AB  - One-stage repair of aortic isthmus atresia, aortic arch hypoplasia and ascending
      aorta aneurysm was performed via a standard midline sternotomy. Ascending
      aortoplasty was performed during a 19-min cardiac arrest. With the heart beating
      and continuous normothermic perfusion of the upper and lower part of the body,
      the aortic arch was then enlarged using the Amato technique and the harvested
      ascending aorta wall as autologous patch. A classical Crafoord procedure then
      restored continuity between the aortic arch and the descending thoracic aorta.

PMID- 12204746
TI  - Intracardiac migration of nitinol TrapEase vena cava filter and paradoxical
      embolism.
AB  - The nitinol TrapEase inferior vena cava filter is a new device for pulmonary
      embolism prophylaxis. No cases of filter migration or filter-related
      complications with this type of device have so far been described. We report a
      case of intracardiac migration of this filter in a patient with a patent foramen
      ovale, resulting in severe cardiogenic shock, cerebral and right arm paradoxical
      embolism. Surgical treatment, results, causes of these complications are
      discussed.

PMID- 12204747
TI  - Acute pulmonary embolism due to the rupture of a right ventricle hydatic cyst.
AB  - Hydatid pulmonary embolism is an uncommon condition resulting from the rupture of
      a hydatid heart cyst or the opening of a visceral hydatid cyst (often in the
      liver) into the venous circulation. We report a case of hydatid pulmonary
      embolism following rupture of a hydatic cyst in the right ventricle. Pulmonary
      angiography showed right pulmonary occlusion. Echocardiography, computed
      tomography scan and magnetic resonance imaging showed images suggesting a hydatid
      cyst. The patient underwent sternotomy and cardiopulmonary bypass in order to
      treat the heart cyst and remove the hydatic pulmonary obstruction. A concomitant
      lung hydatid cyst was extirpated.

PMID- 12204748
TI  - Acquired pulmonary vein obstruction after open-heart surgery.
AB  - Acquired pulmonary vein obstruction is an extremely rare complication after open
      heart surgery not including pulmonary vein procedures. We report on three cases
      of this unusual complication presenting peculiar angiographic findings in order
      to understand its possible etiology.

PMID- 12204749
TI  - Lipomatous interatrial septal hypertrophy: an unusual cause of intracardiac mass.
AB  - Lipomatous hypertrophy of the interatrial septum is an uncommon entity that
      usually occurs in elderly patients. We report a patient who presented with atrial
      fibrillation, congestive cardiac failure and a large intracavitary mass in the
      right atrium on echocardiography. He underwent successful resection of the mass
      with septal reconstruction. Pathology was consistent with lipomatous hypertrophy
      of the interatrial septum.

PMID- 12204750
TI  - Spontaneous rupture of coronary artery.
AB  - We report a case of spontaneous coronary artery rupture (SCAR) 3 months after
      descending aortic replacement. Cardiac tamponade was confirmed at first by using
      echocardiography following emergency pericardial centesis. The patient was denied
      aortic dissection by computed tomography, thereafter diagnosed as SCAR with
      selective angiography, which revealed a leakage from the left circumflex branch.
      The patient underwent successful rupture site isolation by bilateral ligation and
      distal revascularization with aortocoronary bypass with saphenous vein graft.

PMID- 12204751
TI  - Iatrogenic left main and proximal right coronary artery stenoses after aortic
      valve replacement.
AB  - Iatrogenic left main coronary artery stenosis after aortic valve replacement is
      an infrequent but potentially life-threatening complication. A 44-year-old woman
      who had normal coronary arteries documented by preoperative coronary angiogram,
      and who developed severe stenosis of the left main coronary artery and subtotal
      occlusion of the proximal right coronary artery after aortic and mitral valve
      replacements is presented. Coronary lesions were clinically manifested 4 months
      after the first operation. Accurate diagnosis was confirmed by repeat coronary
      angiography. She underwent successful coronary artery bypass grafting.

PMID- 12204752
TI  - Cystic lymphangioma of the heart mimicking a mediastinal tumor.
AB  - Primary cardiac tumors are rare and myxomas are the most frequent. Cystic
      lymphangiomas are most often of cervicomediastinal locations and are exceedingly
      rare in the mediastinum. Cystic lymphangioma involving the heart has never been
      reported. We report a case of cystic lymphangioma involving the posterior wall of
      left atrium mimicking a mediastinal tumor. Complete resection was performed via a
      median sternotomy under cardiopulmonary bypass and cardiac arrest after
      transection of the aorta and pulmonary trunk.

PMID- 12204753
TI  - Appearance of thymoma 15 years after extended thymectomy for myasthenia gravis
      without thymoma.
AB  - Several cases of thymoma recurrence after resection have been reported. However,
      thymoma appearance following an extended thymectomy for non-thymomatous
      myasthenia gravis is very rare. We report a case of thymoma in a 48-year-old
      woman, 15 years after an extended thymectomy for non-thymomatous myasthenia
      gravis. The importance of a complete dissection of mediastinal adipose tissue
      during the extended thymectomy as well as careful follow-up for such patients is
      also noted.

PMID- 12204754
TI  - Unusual presentation of mucoepidermoid carcinoma with recurrent pulmonary
      embolism.
AB  - Mucoepidermoid carcinoma is a rare type of tumor of bronchial glands. We describe
      an unusual presentation of mucoepidermoid carcinoma in a 19-year-old man with
      atypical pneumonia, deep vein thromboses and recurrent pulmonary embolism, which,
      to the best of our knowledge has not previously been reported.

PMID- 12204755
TI  - Routine mediastinoscopy and lymph node staging: 'much ado about nothing'?

PMID- 12204757
TI  - Esophageal foreign bodies.

PMID- 12204759
TI  - Perivenous application of fibrin glue reduces early injury of the human saphenous
      vein graft wall in an ex vivo model.

PMID- 12204761
TI  - A foreign body reaction to Surgicel mimicking an abscess following cardiac
      surgery.

PMID- 12204763
TI  - Clinical relevance of microembolic signals in patients with prosthetic heart
      valves.

PMID- 12204764
TI  - Reduced vascular complication after IABP insertion using smaller sized catheter
      and sheathless technique.

PMID- 12204766
TI  - What can be an indicator of delayed sternal closure after cardiac surgery?

PMID- 12204768
TI  - Adenosine production and its interaction with protection of ischemic and
      reperfusion injury of the myocardium.
AB  - Adenosine exerts cardioprotective effects on the ischemic myocardium. A flexibly
      mounted microdialysis probe was used to measure the concentration of interstitial
      adenosine and to assess the activity of ecto-5'-nucleotidase (a key enzyme
      responsible for adenosine production) in in vivo rat hearts. The level of
      adenosine during perfusion of adenosine 5'-adenosine monophosphate (AMP) was
      given as an index of the activity of ecto-5'-nucleotidase in the tissue.
      Endogenous norepinephrine (NE) activates both alpha(1)-adrenoceptors and protein
      kinase C (PKC), which, in turn, activates ecto-5'-nucleotidase via
      phosphorylation thereby enhancing the production of interstitial adenosine.
      Histamine-release NE activates PKC, which increased ecto-5'-nucleotidase activity
      and augmented release of adenosine. Opening of cardiac ATP sensitive K(+)
      (K(ATP)) channels may cause hydroxyl radical (.OH) generation through NE release.
      Lysophosphatidylcholine (LPC), an endogenous amphiphiphilic lipid metabolite,
      also increases the concentration of interstitial adenosine in rat hearts, through
      the PKC-mediated activation of endogenous ecto-5'-nucleotidase. Nitric oxide (NO)
      facilitates the production of interstitial adenosine, via guanosine 3',5'-cyclic
      monophosphate (cGMP)-mediated activation of ecto-5'-nucleotidase as another
      pathway. These mechanisms play an important role in high sensitivity of the
      cardiac adenosine system. Adenosine plays an important role as a modulator of
      ischemic reperfusion injury, and that the production and mechanism of action of
      adenosine are linked with NE release.

PMID- 12204769
TI  - Hwangryun-Hae-Dok-tang (Huanglian-Jie-Du-Tang) extract and its constituents
      reduce ischemia-reperfusion brain injury and neutrophil infiltration in rats.
AB  - The preventive effect of Hwangryun-Hae-Dok-tang (HHDT, Huanglian-Jie-Du-Tang), a
      Chinese herbal medicine, and its ingredients on ischemia/reperfusion-induced
      brain injury was evaluated in the rat brain. HHDT consists of four herbs, namely,
      Coptidis rhizoma, Scutellariae radix, Phellodendri cortex, and Gardeniae fructus.
      Ischemia was induced by intraluminal occlusion of the right middle cerebral
      artery for 120 min and reperfusion was continued for 22 h. HHDT (200 mg/kg),
      Coptidis rhizoma (100 mg/kg), Scutellariae radix (100 mg/kg), Phellodendri cortex
      (100 mg/kg), and Gardeniae fructus (100 mg/kg) were orally administered, promptly
      prior to reperfusion and 2 h after reperfusion. Baicalein, a component of
      Scutellariae radix, was also examined at a dosage of 50 mg/kg given 2 h apart,
      promptly prior to and 2 h after reperfusion. Total infarction volume in the
      ipsilateral hemisphere of ischemia/reperfusion rats was significantly lowered by
      treatment with HHDT, Scutellariae radix, and balicalein. However, the other
      ingredient of HHDT did not show any ameliorating effects on total infarction
      volume. The inhibiting effect of Scutellariae radix on total infarction volume
      was much higher than that of the others. In addition, HHDT, Scutellariae radix,
      and baicalein significantly inhibited myeloperoxidase (MPO) activity, an index of
      neutrophil infiltration in ischemic brain tissue at about the same rate (30%).
      There was marked mismatch between total infarction volume and MPO activity in the
      Scutellariae radix-treated rats but not in the HHDT- and baicalein-treated
      groups. Our findings suggest that Scutellariae radix as an ingredient of HHDT
      plays a crucial protective role in ischemia-induced brain injury. In addition, it
      is apparent that the effect of Scutellariae radix is the result, in part, of
      baicalein, a compound contained in Scutellariae radix.

PMID- 12204770
TI  - Glucose-induced alterations of intracellular ionized magnesium in human
      lymphocytes.
AB  - The intracellular ionic content of human erythrocytes may be altered by
      hyperglycaemia. Despite this, very little is known about the cellular mechanisms
      linking glucose and cellular magnesium homeostasis. We measured intracellular
      ionized magnesium in human lymphocytes, by means of a fluorimetric technique,
      total intracellular magnesium by means of atomic absorption spectrophotometry and
      intracellular ATP by means of HPLC. The incubation of lymphocytes with D-glucose
      in the absence of insulin was followed by a significant decrease in intracellular
      ionized magnesium; this effect did not occur when the cells were incubated with L
      glucose. The effect of glucose on intracellular ionized magnesium was blocked by
      amphotericin B and the EC(50) of the effect of glucose on intracellular ionized
      magnesium was about 5 mmol/l of glucose. The increase of intracellular ionized
      magnesium in cells incubated in the absence of glucose was followed by a decrease
      in intracellular ATP. In a Na(+)-free medium the decrease of intracellular
      ionized magnesium in the presence of glucose was still present and the incubation
      of lymphocytes with glucose did not modify total intralymphocyte magnesium. By
      selective permeabilization of cell membranes, we established that glucose could
      not increase compartmentalized intracellular ionized magnesium. Our data supports
      the hypothesis that glucose per se induces a substantial decrease in
      intracellular ionized magnesium, which is probably due to an augmented binding of
      intracellular ionized magnesium to cellular ATP.

PMID- 12204771
TI  - Stimulation of the catecholaminergic and serotoninergic neurons in the rat brain
      by R-(-)-1-(benzofuran-2-yl)-2-propylaminopentane, (-)-BPAP.
AB  - R-(-)-1-(Benzofuran-2-yl)-2-propylaminopentane HCl, (-)-BPAP, the recently
      developed selective and much more potent catecholaminergic/serotoninergic
      enhancer (CAE/SAE) substance than (-)-deprenyl enhances the performance of
      midbrain neurons, both in vivo and ex vivo, in a characteristic complex manner,
      presenting one bell shape dose/concentration effect curve in the low nanomolar
      range and another at higher micromolar range. For example, 4.7 +/- 0.10 nmol/g
      wet weight noradrenaline was released within 20 min from the quickly removed
      locus coeruleus of saline treated rats. This amount was increased 30 min after
      the subcutaneous administration of 0.0005 mg/kg (-)-BPAP to 15.4 +/- 0.55 nmol/g
      (P < 0.001). However, following the injection of a hundred times higher, 0.05
      mg/kg, dose of (-)-BPAP, the amount of noradrenaline (4.3 +/- 0.25 nmol/g)
      released from the locus coeruleus did not differ from the control value. In ex
      vivo experiments, when the isolated locus coeruleus was soaked in an organ bath
      containing (-)-BPAP, the release of noradrenaline was significantly enhanced from
      10(-16) M concentration, reached a peak effect at 10(-13) M concentration, but
      10(-10) M (-)-BPAP was ineffective. A significant enhancer effect was detected
      also in the high concentration range from 10(-8) M, the peak effect was reached
      at 10(-6) M concentration and 10(-5) M (-)-BPAP was ineffective. (-)-BPAP
      enhanced in the low concentration range the performance of dopaminergic and
      serotoninergic neurons with a peak effect at 10(-13) and 10(-12) M concentration,
      respectively. The results with (-)-BPAP, the highly specific artificial enhancer
      substance, suggest that (i) high and low affinity "enhancer" receptors may exist
      in the brain, and (ii) that they may be identified with the recently cloned
      family of the "trace amine" receptors, activated by beta-phenylethylamine and
      tryptamine, the prototypes of the endogenous enhancer substances.

PMID- 12204772
TI  - Inhibition of protein kinase CKII activity by resveratrol, a natural compound in
      red wine and grapes.
AB  - Resveratrol is a phytoalexin found in grapes and other foods that has been shown
      to have anticancer and anti-inflammatory effects. Because protein kinase CKII is
      involved in cell proliferation and oncogenesis, we examined whether resveratrol
      could modulate CKII activity. Resveratrol was shown to inhibit the
      phosphotransferase activity of CKII with IC(50) of about 10 microM. Steady state
      studies revealed that resveratrol acted as a competitive inhibitor with respect
      to the substrate ATP. A value of 1.2 microM was obtained for the apparent K(i).
      Resveratrol also inhibited the catalytic reaction of CKII with GTP as substrate.
      Furthermore, resveratrol inhibits endogenous CKII activity on protein substrates
      in HeLa cell lysates. These results suggest that resveratrol is likely to
      function by inhibiting oncogenic disease, at least in part, through the
      inhibition of CKII activity.

PMID- 12204773
TI  - Influence of serum supplements in culture medium on gonadotropin-releasing
      hormone effects on colony formation.
AB  - A number of studies have demonstrated that GnRH has anti-proliferative effects on
      various carcinomas of breast, ovary, endometrium, prostate, pancreas, and liver
      origin. In contrast, GnRH increases the proliferative activity of lymphoid
      tissues and cells, which suggests that GnRH is also an important immunomodulator.
      In a previous study, we demonstrated that the colony-forming efficiencies of HHUA
      (derived from human endometrial carcinoma) and Jurkat (derived from human mature
      leukemia) cells are affected by the GnRH agonist Buserelin, and that the
      conditioned media of HHUA and Jurkat cells severely affect the Buserelin
      activity. The latter finding suggests that substances in the culture medium have
      some relation to the GnRH activity. Therefore, in the present study, to evaluate
      the effect of serum supplements on the colony-forming efficiency assay, the assay
      was performed using 3 lots of fetal bovine serum (FBS) and 2 lots of Nu-Serum I,
      a semi-synthetic serum supplement. The results showed that the colony-forming
      efficiencies of HHUA and Jurkat cells fluctuated greatly depending on the lot of
      FBS. In contrast, Buserelin significantly affected the colony-forming efficiency
      to similar extents in the media containing both the lots of Nu-Serum I. These
      results strongly suggest that the constituents of the serum supplements also
      influence the effect of GnRH on cell proliferation. For further studies about the
      relationship between substances in the culture medium and the GnRH effects on
      cell proliferation, it will be necessary to use a completely defined medium, and
      that a semi-synthetic serum supplement such as Nu-Serum I will also be useful.

PMID- 12204774
TI  - Anticancer activity of Hemsleya amabilis extract.
AB  - Hemsleya amabilis extract is derived from the medicinal herb Hemsleya amabilis,
      which has long been used to treat cancer and many other conditions. The
      underlying mechanism is not clear. To investigate Hemsleya amabili's anticancer
      activity, we have treated different types of cancer cells including human
      astrocytoma U87 cells, breast cancer cells MDA-MB-231and Jurkat cells with
      Hemsleya amabilis extract. This agent significantly inhibited tumor cell growth
      and colony formation at various concentrations. When astrocytoma cells were
      seeded in the presence of Hemsleya amabilis extract at very low concentrations,
      cell spreading was greatly inhibited. Hemsleya amabilis extract also promoted
      tumor cell death in all the tested cell lines, but with varied sensitivities.
      Apoptotic assays with Annexin V staining demonstrated that Hemsleya amabilis
      extract induced astrocytoma cell apoptosis at different concentrations.

PMID- 12204775
TI  - Involvement of microphthalmia-associated transcription factor (MITF) in
      expression of human melanocortin-1 receptor (MC1R).
AB  - Analysis of the nucleotide sequence of human melanocortin-1 receptor (MC1R)
      promoter indicated that an E-box (CANNTG) is present immediately upstream of the
      transcriptional initiation site. The presence of the CATGTG motif suggests that
      MC1R gene expression may be regulated by a basic helix-loop-helix-leucine-zipper
      (bHLH-LZ) type transcription factor. The microphthalmia-associated transcription
      factor (MITF), which belongs to the family of bHLH-LZ type transcription factors,
      regulates the transcription of melanogenesis-related enzyme genes such as the
      tyrosinase and TRP-1 genes. We investigated whether MITF regulates human MC1R
      gene expression through the same transcriptional mechanism as tyrosinase and TRP
      1 genes in melanocytes. For this purpose, the effect of co-expression of cDNA
      encoding MITF on MC1R promoter activity in NIH/3T3 cells was studied. MC1R
      promoter activity was induced to the extent of approximately 5-fold in the
      presence of MITF. In addition, electrophoretic mobility shift assay indicated
      that nuclear extracts of human SK-Mel-2 cells contain a protein that binds
      specifically to the MC1R promoter region containing the CATGTG motif. These
      results suggested that MITF regulates not only the expression of enzymes involved
      in melanin synthesis, but also the expression of a receptor which plays an
      essential role in melanocyte functions.

PMID- 12204776
TI  - 17Beta-estradiol inhibits the adhesion of leukocytes in TNF-alpha stimulated
      human endothelial cells by blocking IL-8 and MCP-1 secretion, but not its
      transcription.
AB  - Inflammation, and especially mononuclear cell adhesion to endothelium, is an
      important physiopathological component of atherosclerosis. Since coronary heart
      disease in women of reproductive age and/or with estrogen replacement therapy is
      reduced, our aim was to determine if 17beta-estradiol had a regulatory effect on
      the adhesion of lymphocytes to the endothelium. We performed U-937 cells adhesion
      assays in TNF-alpha-stimulated HUVECs, and we also quantitated IL-8 and MCP-1 in
      culture supernatants, in the presence or not of 17beta-estradiol. The presence of
      alpha- and beta-estrogen receptors was determined by Western blot and RT-PCR,
      respectively, whereas the transcription of both chemokines was evaluated by RT
      PCR. The results showed a 35% decrease in the adhesion of U-937 monocyte cells to
      TNF-alpha-stimulated HUVECs, and a 54% and 65% inhibition of TNF-alpha-induced IL
      8 and MCP-1 secretion by physiological and physiologically high doses of 17beta
      estradiol. The hormone did not affect the transcription of both chemokine genes.
      Tamoxifen reverted the inhibitory effect induced by 17beta-estradiol. In
      conclusion, 17beta-estradiol modifies the adhesion of leukocytes to endothelial
      cells by inhibiting the secretion, but not the gene transcription, of
      proinflammatory chemokines.

PMID- 12204777
TI  - Increased local angiotensin II formation in aneurysmal aorta.
AB  - We investigated the levels and locations of angiotensin II-forming enzymes,
      angiotensin converting enzyme (ACE) and chymase, in aneurysmal and normal aortas.
      Aneurysmal aortic specimens (n = 14) were obtained at the time of operative
      aneurysm repair from 14 patients ranging in age from 57 to 84 y. Normal aortic
      specimens (n = 16) were obtained from 16 patients (48 to 72 y) who underwent
      coronary artery bypass surgery. The ACE and chymase activities were determined
      using each specimen. Sections of each specimen were immunostained with antibodies
      for ACE and chymase. The ACE activities in the aneurysmal and normal aortas were
      0.82 +/- 0.10 and 0.14 +/- 0.05 mU/mg protein, respectively, and this difference
      was significant. The chymase activities in the aneurysmal and normal aortas were
      17.9 +/- 2.40 and 1.02 +/- 0.18 mU/mg protein, respectively, and this difference
      was also significant. In the aneurysmal aorta, ACE-positive cells were detected
      with macrophages in the intima and media and chymase-positive cells were detected
      with mast cells in the media and adventitia, whereas positive ACE and chymase
      cells in the normal aorta were located only in the endothelium and adventitia,
      respectively. Angiotensin II-forming enzymes, chymase and ACE, were significantly
      increased in the aneurysmal aorta, and increased angiotensin II may be associated
      with the development of aneurysmal formations.

PMID- 12204778
TI  - Oral contraception and epilepsy: findings in a large cohort study.
AB  - There is no good evidence that oral contraceptives (OCs) increase the risk of
      epilepsy in unaffected women or increase the frequency of seizures in those
      suffering from the disorder. Nonetheless, manufacturers' literature continues to
      include warnings about OCs and epilepsy. We have analyzed the available data
      about epilepsy in the Oxford-Family Planning Association contraceptive study that
      includes 17,032 women followed for periods of up to 26 years. In total, 82 women
      (with no record of having suffered epilepsy when recruited to the study) were
      referred to hospital for diagnosis or treatment of epilepsy during the follow-up
      period. No association was found between OC use and the occurrence of the
      condition. Referral to hospital was, however, more frequent in women of low
      social class and in those with a high body mass index.

PMID- 12204779
TI  - Adolescent compliance and side effects with Quick Start initiation of oral
      contraceptive pills.
AB  - Adolescents' compliance with use of oral contraceptive pills has been described
      in the literature. The purpose of this study was to compare traditional Sunday
      Start to a same day (Quick Start) approach. A retrospective study of patients 22
      years of age and younger was performed comparing compliance at 3 months and 12
      months and side effects. The groups were divided into Quick Start (N = 77, 40%)
      and Sunday Start (N = 116, 60%). One hundred twenty-five (65%) patients were
      compliant at 3 months; 68 patients (35%) were compliant at 12 months. Quick Start
      users were more likely to comply at 3 months (72% vs. 56%, p = 0.059), especially
      if they were Caucasian (80% vs. 65%, p = 0.007), with dysmenorrhea (86% vs. 62%,
      p = 0.006), nulligravid (77% vs. 58%, p = 0.008), or nulliparous (73% vs. 59%, p
      = 0.038). There was no difference in side effects. There was no significant
      difference at 1 year in compliance or side effects. Findings suggest better
      compliance in adolescents at 3 months with the Quick Start approach while
      maintaining side effect profile.

PMID- 12204780
TI  - HIV infection in women: impact on contraception.
AB  - A study was performed to evaluate the impact of knowledge of HIV infection
      (diagnosis) on contraception information and choices for HIV infected women. A
      questionnaire was given to 140 HIV infected women. Most of the studied population
      included young women with a low educational level. A significant increase in the
      knowledge of contraceptive methods was observed after diagnosis of being HIV
      infected. The data suggested that the women who received information had never
      received it before, or that the diagnosis created a stronger motivation to listen
      to the counseling offered. A significant increase in the use of contraceptive
      methods was also found, especially male condoms and tubal ligation. Total number
      of children had a strong impact on contraceptive method at the time of interview.
      Only 5 of 23 HIV infected women who had no children used hormonal contraceptives,
      while 15 of 23 preferred condom use, and 3 of 23 chose not to use any
      contraceptive method. Tubal ligation was performed in approximately 9% of the
      women who had only one child. However, 12.4% of the sexually active HIV infected
      women were still not using any contraceptive method at the time of the interview.
      A combined method (male condom plus another contraceptive) was used by only 27%
      of sexually active HIV infected women, despite health service counseling. In
      conclusion, the realization of being HIV infected had a strong impact on
      contraceptive practice among these women. It is expected that HIV and family
      planning clinics will address HIV infected women's needs and be prepared to
      integrate contraception and gynecological care.

PMID- 12204781
TI  - Contraception and treatment in the perimenopause with a novel "frameless"
      intrauterine levonorgestrel-releasing drug delivery system: an extended pilot
      study.
AB  - The objective of the study was to evaluate the contraceptive performance,
      acceptability, side effects, and adverse events of a novel "frameless"
      intrauterine drug delivery system (IUS), FibroPlant-levonorgestrel (LNG)
      releasing 14 microg of LNG/day, in perimenopausal women. An ancillary objective
      was to evaluate the effect of the new IUS on menstrual blood loss in women with
      or without fibroids. The study, consisting of 109 women, suggests that FibroPlant
      LNG IUS is an effective contraceptive. No pregnancies occurred with the
      FibroPlant-LNG IUS. The total use-related discontinuation rate at 1 year is low
      (1.9) and results in a high rate of continuation of use (98.1). In addition, the
      FibroPlant-LNG IUS demonstrated a high level of effectiveness in reducing
      bleeding in women with excessive menstrual flow even when medium or large
      fibroids were present. However, an effect on the size of the fibroids could not
      be demonstrated. Patient satisfaction with the method is high, which is a
      prerequisite for continuance of the method, and may be linked with the
      advantageous design characteristics of the FibroPlant-LNG IUS, the virtual
      absence of hormonal side effects, and the low incidence of irregular bleeding and
      spotting even during the first 3 months after insertion of the FibroPlant IUS.
      Counseling remains important though to explain to women about the possible
      occurrence of changes in their menstrual pattern that may sometimes be annoying
      but harmless. It is concluded that many women over age 40 years could
      substantially benefit from the advantages of this intrauterine drug delivery
      technology which provides contraception and treatment of a possible associated
      condition such as menorrhagia. The treatment also creates the opportunity to pass
      through the transitional perimenopausal period smoothly and to benefit fully from
      the advantages hormone replacement therapy offers in terms of treatment of short
      term symptoms and long-term prevention by gradually replacing the waning
      estrogens.

PMID- 12204782
TI  - Bone mineral density in adolescent and young Thai girls receiving oral
      contraceptives compared with depot medroxyprogesterone acetate: a cross-sectional
      study in young Thai women.
AB  - This cross-sectional study of bone mineral density in adolescent and young Thai
      girls receiving oral contraceptives compared with depot medroxyprogesterone
      acetate was performed to evaluate the differences among these groups. Thirty
      current OC users and 30 current depot medroxyprogesterone acetate (DMPA) users
      were included in the study. The mean duration of OC use was 28.8 +/- 3.4 months
      and of DMPA 24.6 +/- 3.3 months. Dual energy X-ray absorptiometry (DEXA) was used
      to measure bone mineral density (BMD) at distal and ultradistal forearm of the
      nondominant side. The BMD of ultradistal forearm of OC users and that of DMPA
      users were 0.423 +/- 0.048 and 0.403 +/- 0.039 g/cm(2) and at distal forearm of
      OC and DMPA users were 0.566 +/- 0.043 and 0.571 +/- 0.064 g/cm(2), respectively.
      However, there were no statistical differences in BMD in these two groups.

PMID- 12204783
TI  - Extrauterine mislocated IUD: is surgical removal mandatory?
AB  - The incidence of intrauterine device perforation is 0.87 per 1000 insertions. An
      intrauterine device (IUD) may perforate through the uterine wall into the pelvic
      or abdominal cavity or into adjacent organs. The accepted treatment for displaced
      IUDs is surgical removal because of the putative risk of adhesion formation or of
      damage to the intestine or urinary bladder. The purpose of this article is to
      present three cases of IUD perforation where surgical removal may not have been
      necessary. In all three cases, the IUD was removed by laparoscopy. No adhesions
      were found in any of the patients. Criteria for the surgical removal of a
      displaced IUD, as a result of uterine perforation, should be re-evaluated. Whilst
      surgical procedures to remove a misplaced IUD must be performed on symptomatic
      patients, asymptomatic patients, under certain circumstances, may benefit from
      conservative management.

PMID- 12204784
TI  - Contraceptive failure--results from a study conducted among women with accepted
      and unaccepted pregnancies in Denmark.
AB  - Most studies focusing on contraceptive failure in relation to pregnancy have
      focused on contraceptive failure among women having induced abortions, thereby
      neglecting those women who, despite contraceptive failure, accept the pregnancy
      and intend to carry the fetus to term. To get a more complete picture of the
      problem of contraceptive failure, this study focuses on contraceptive failure
      among women with diverse pregnancy outcomes. In all, 3520 pregnant women
      attending Odense University Hospital were included: 373 had induced abortions,
      435 had spontaneous abortions, 97 had ectopic pregnancies, and 2614 received
      antenatal care. The variables studied comprise age, partner relationship, number
      of births, occupational and economical situation, and contraceptive
      use.Contraceptive failure, defined as contraceptive use (condom, diaphragm, IUD,
      oral contraception, or another modern method) at the intercourse where conception
      most likely occurred, were reported by 315 women, 52% of these women had induced
      abortions, 10% had spontaneous abortions, 3% had ectopic pregnancies, and 36%
      received antenatal care. Women aged 15-24 years were more likely to have
      experienced contraceptive failure in relation to use of condom and oral
      contraception than women aged 25-34 years. In addition, contraceptive failure was
      found to be associated with being single, a student, and having given birth twice
      or more previously. Regarding pregnancy acceptance, being 25-34 years of age was
      positively associated, whereas being single and a student was negatively
      associated with pregnancy acceptance.

PMID- 12204785
TI  - Attitudes of mothers toward their daughters' use of contraceptives in Israel.
AB  - The objective of the study was to examine mothers' knowledge about contraception,
      their attitudes to their daughters' use of contraception, and their communication
      with their daughters on the subject. A 20-item questionnaire was distributed in
      gynecological clinics throughout Israel for completion by women who had daughters
      over the age of 14 years. The questionnaire covered the mothers' demographic
      data, use of contraception, knowledge of contraception, attitude to their
      daughters' contraceptive use and sexual relationships, and communication with
      their daughters about contraception. Only 36% of the women received contraceptive
      information from physicians. Almost half felt their daughter should begin sexual
      relations when she felt she was ready; over two-thirds felt she should begin
      using contraception before or at the time of beginning sexual relations. Over
      three-quarters spoke with their daughters about contraception. Higher educational
      level of the mother was associated with high rate use of contraception by the
      mother, her support of earlier use of contraception by her daughter, a greater
      likelihood of her discussing contraception with her daughter, and a lesser
      likelihood to view contraceptives as dangerous to one's health. It is concluded
      that mothers of teenage daughters in Israel are involved in their daughters'
      decisions to begin sexual relations and the use of contraceptives. Their
      knowledge of contraception is adequate, although some gaps are still apparent.
      Clear correlation is found between higher educational level of the mothers and a
      more liberal attitude toward their daughters' sex life.

PMID- 12204786
TI  - Acceptability of the levonorgestrel-releasing intrauterine system after
      discontinuation of previous contraception: results of a French clinical study in
      women aged 35 to 45 years.
AB  - This open, noncomparative study evaluated the rate of premature removals of the
      levonorgestrel-releasing intrauterine system (LNG-IUS) Mirena because of adverse
      events. To take part in the study, women had to be aged between 35 years and 45
      years, and had to change their contraception for poor compliance, poor tolerance,
      or unfavorable change in the benefit/risk ratio of their previous contraception
      (oral contraceptives or copper- or progestin-releasing intrauterine device). One
      removal of Mirena for a wish for pregnancy was excluded from analyses, so that
      there were 23 removals among 203 women included. The survival ratio was 88.7%,
      which corresponds to a 1-year rate of premature removals of 11.3%. No
      statistically significant difference was found between women switched from IUD
      and women switched from oral contraception regarding the continuation rate (p =
      0.640, log-rank test) and the discontinuation rate (p = 0.430, chi(2) test). The
      main reasons for premature removal were bleeding problems (11 subjects including
      2 amenorrhea, 5.4%), pain (5 subjects, 2.5%), and acne (2 subjects, 1%). Two
      premature discontinuations occurred after accidental removal. The number of
      bleeding or spotting days significantly decreased from baseline (p < 0.001), and
      gynecological symptoms were alleviated. Hematocrit, hemoglobin levels, and serum
      ferritin increased significantly. No pregnancies occurred. Acne and irregular
      bleedings were the most frequent adverse events. The results show the excellent
      acceptability as well as the favorable efficacy/safety ratio of the LNG-IUS
      Mirena in older reproductive age women whatever the primary method of
      contraception.

PMID- 12204787
TI  - Cervical mucus granulocyte macrophage colony stimulating factor and interleukin-2
      soluble receptor in women using copper intrauterine contraceptive devices.
AB  - This study was undertaken to investigate the role of cytokines in intrauterine
      contraception. Cervical mucus samples were obtained from 20 women with proven
      fertility 7, 14, 30, and 120 days after insertion of copper-T380 intrauterine
      devices (IUDs) for the determination of interleukin-2 (IL-2) soluble receptor (IL
      2SR) and granulocyte macrophage colony stimulating factor (GM-CSF)
      concentrations. Both levels of IL-2SR and GM-CSF were significantly elevated
      after insertion of copper-releasing IUDs. This elevation remained significant
      through 6 months post-insertion. The mean-fold rise of GM-CSF compared to pre
      insertion mean values amounted to 12.4, 11.8, 2.1, and 1.5 at 7, 14, 30, and 120
      days post-insertion, respectively. The corresponding values for IL-2SR were 10.4,
      8.8, 2.6, and 2.5, respectively. These results demonstrate enhanced local
      cytokines production in IUD users indicating local inflammatory reaction in the
      endometrium. This inflammatory reaction together with the cytotoxic effects of
      these cytokines may produce an environment which adversely affect embryo pre
      implantation. This may explain the antifertility effect of copper IUDs.

PMID- 12204788
TI  - Penile application of dextrin sulphate gel (Emmelle).
AB  - Dextrin sulphate (DS) gel (Emmelle) is under development as a vaginal
      microbicide. Males who do not use condoms will be exposed to DS gel through
      sexual intercourse. A randomized, double-blind, placebo-controlled trial was
      conducted among 16 HIV-positive and 12 HIV-negative men to establish whether 4%
      DS gel has an acceptable safety profile. Men were asked to apply the gel to the
      penis once per day for 14 consecutive days and to leave it on for a minimum of 6
      h. Results from laboratory evaluations, genital examinations, and adverse events
      reports showed that 4% DS gel administered topically to the penis was well
      tolerated when compared with placebo.

PMID- 12204789
TI  - Synthetic cervical mucus formulation.
AB  - A synthetic formulation has been developed with viscosity, spinnbarkeit, and pH
      comparable to that reported for human cervical mucus. The formulation contains
      guar gum crosslinked with borate ion, mucin (dried porcine gastric), and a mixed
      preservative system in pH 7.4, 0.1M phosphate buffer. The guar gum source, mucin
      concentration, and method of preparation were shown to be critical factors in the
      performance of the formulation.

PMID- 12204790
TI  - The use of antioxidant supplements in coronary heart disease.
AB  - There is clear evidence of lipoprotein oxidation in atherosclerotic lesions.
      Animal studies and observational prospective human cohort studies have been
      interpreted as supporting a role for antioxidants in the prevention of coronary
      heart disease (CHD). However, firm recommendations to take antioxidant
      supplements to treat or prevent CHD require evidence derived from randomised
      controlled studies. In primary prevention studies, low dose alpha-tocopherol does
      not reduce the incidence of coronary events (ATBC study), and beta-carotene
      either has no effect or increases the incidence of coronary events and cancer
      death (ATBC, CARET, Physician's Health studies). Secondary preventions, those
      with smaller populations and shorter duration of follow up have shown some
      benefit from alpha-tocopherol (CHAOS, SPACE), but larger randomised studies
      indicate no benefit from treatment with alpha-tocopherol (HOPE, GISSI, PPP).
      Recent studies with antioxidant combinations also show no benefit (HATS, MPS). On
      the basis of these data, supplements of alpha-tocopherol and beta-carotene cannot
      be recommended for the treatment or prevention of CHD. Fundamental and applied
      research may yet find a role for antioxidant supplements in the treatment of
      coronary disease. However, this will require positive results from combined
      antioxidant studies currently in progress, and the targeting of oxidative
      processes that operate in the artery wall and cause or contribute to disease.

PMID- 12204791
TI  - Effect of gemfibrozil on apolipoprotein B secretion and diacylglycerol
      acyltransferase activity in human hepatoblastoma (HepG2) cells.
AB  - The mechanism of action of a widely used drug gemfibrozil to reduce triglycerides
      (TG) and apolipoprotein B (apo B) is incompletely understood. Using human
      hepatoblastoma (HepG2) cells, we examined the effect of gemfibrozil on apo B
      secretion and TG synthesis catalyzed by diacylglycerol acyltransferase (DGAT),
      primary processes associated with the secretion of LDL. Gemfibrozil significantly
      decreased apo B secretion by HepG2 cells. It decreased oleate-induced stimulation
      of apo B secretion, suggesting that gemfibrozil-mediated inhibition of apo B
      secretion may be dependent on the synthesis of TG catalyzed by DGAT. Pre
      incubation of HepG2 cells with gemfibrozil (200-400 micromol/l for 48 h)
      significantly inhibited microsomal DGAT activity. When added directly to the DGAT
      assay system containing control microsomes, gemfibrozil significantly inhibited
      the activity of DGAT by 14-25%. Gemfibrozil (200-400 micromol/l) inhibited TG
      synthesis by 47-50% as measured by the incorporation of 3H-oleic acid into TG.
      The data indicate that gemfibrozil inhibits DGAT activity resulting in decreased
      synthesis of TG and its availability for apo B lipidation rendering it
      susceptible to intracellular apo B degradation leading to the decreased
      secretion. These in-vitro data suggest a novel additional mechanism by which
      gemfibrozil lowers plasma TG and atherogenic apo B lipoproteins in dyslipidemic
      patients.

PMID- 12204792
TI  - Effect of dietary copper supplementation on cell composition and apoptosis in
      atherosclerotic lesions of cholesterol-fed rabbits.
AB  - We have previously shown that dietary copper supplementation modulates the
      formation of atherosclerotic lesions in the cholesterol-fed rabbit. In the
      present study, we have investigated the effects of copper supplementation on the
      cellular composition and characteristics of atherosclerotic lesions in
      cholesterol-fed NZW rabbits. Rabbits received a 1% cholesterol diet with or
      without 0.02% copper acetate (containing 12 and 0.3 mg copper per 100 g diet,
      respectively) for 12 weeks. The tunica intima was significantly smaller in the
      animals receiving copper supplements (0.016+/-0.005 vs. 0.068+/-0.019 mm(2),
      P<0.05) and this was accompanied by a significant increase in aortic copper
      content (4.0+/-0.8 vs. 1.8+/-0.2 microg/g tissue, P<0.05). The percentage area
      staining for smooth muscle cells (HHF-35 positive) was significantly lower in the
      intima of animals receiving copper supplements (7.13+/-1.02 vs. 9.72+/-0.82%,
      P<0.05). However, there were no significant differences in area staining for
      macrophages (RAM-11 positive) between groups (22.6+/-7.9 vs. 23.3+/-4.9%). There
      were also significantly fewer apoptotic cells (0.96+/-0.33 vs. 2.54+/-0.56%,
      P<0.005) in the aortic intima from animals supplemented with copper, but no
      difference in the number of proliferating cells. However, there was a reduction
      in intimal collagen staining (Sirius red positivity) in the animals receiving a
      copper supplement. Taken together, these data show that dietary copper can
      significantly affect the composition and progression of atherosclerotic lesions.

PMID- 12204793
TI  - D-erythro-N,N-dimethylsphingosine inhibits bFGF-induced proliferation of
      cerebral, aortic and coronary smooth muscle cells.
AB  - The role of sphingosine kinase (SphK) on basic fibroblast growth factor (bFGF)
      induced proliferation of cerebral, aortic and coronary smooth muscle cells (SMC)
      was addressed using D-erythro-N,N-dimethylsphingosine (DMS), an inhibitor of SphK
      which blocks conversion of sphingosine to sphingosine-1-phosphate (S1P). DMS
      concentration-dependently reduced the bFGF-induced proliferation of rat cerebral
      and aortic, and human coronary SMC. This suggests that SphK is one of the key
      enzymes in the mitogenic response to bFGF in vascular SMC as supported by the
      finding that S1P stimulated proliferation of SMC. Fumonisin B1, a
      dihydroceramidesynthase inhibitor which blocks the conversion of
      dihydrosphingosine to seramide, did not affect SMC proliferation induced by bFGF.
      Staurosporine, an inhibitor of protein kinase C (PKC), inhibited proliferation of
      SMC induced by bFGF, and both bFGF- and S1P-induced proliferation of SMC was
      sensitive to pertussis toxin (PTX), an inhibitor of Gi-protein activity. The
      present study thus demonstrates that SphK, PKC and Gi-protein activities are
      required for bFGF-mitogenic signaling in SMC. The bFGF mitogenic effect in
      vascular SMC might at least in part act via the SphK pathway and a Gi-protein.

PMID- 12204794
TI  - ABCA1(Alabama): a novel variant associated with HDL deficiency and premature
      coronary artery disease.
AB  - The ATP-binding cassette transporter, ABCA1, is a member of the ABC superfamily
      of proteins involved in the active transport of substrates across cellular
      membranes. Recent studies have implicated mutations in ABCA1 as the cause of
      Tangier disease (TD) and familial hypoalphalipoproteinemia (FHA). To evaluate the
      molecular basis of low high density lipoprotein (HDL) in a family with premature
      coronary artery disease, single strand conformational polymorphism analysis was
      performed for all coding regions and splice site junctions of ABCA1 with the
      genomic DNA of the proband. The proband and affected individuals were
      heterozygotes for C254T with proline converted to leucine (P85L). This mutation
      was not identified in over 400 chromosomes of healthy subjects. In the FHA
      kindred, family members heterozygous for the ABCA1 variant also exhibited
      corresponding low levels of HDL cholesterol. These data confirm recent data that
      a single defective allele in ABCA1 may be associated with reduced HDL cholesterol
      and FHA.

PMID- 12204795
TI  - Estrogen inhibits the initiation of fatty streaks throughout the vasculature but
      does not inhibit intra-plaque hemorrhage and the progression of established
      lesions in apolipoprotein E deficient mice.
AB  - Estrogen has previously been shown to inhibit development of early
      atherosclerotic lesions in hyperlipidemic mice. However, it is still not known
      whether estrogen also inhibits progression and destabilization of lesions once
      established and whether there are other effects of long-term hormone therapy in
      mice. To address this question, male, 20-week old, apolipoprotein E deficient
      mice were administered 17-beta estradiol or placebo subcutaneously for between 4
      and 40 weeks. Estrogen administration did not cause regression of established
      lesions in the carotid arteries, aortic arch and thoracic aorta but prevented the
      initiation of new lesions in the abdominal aorta and iliac, femoral and popliteal
      arteries. Although the established lesions were slightly smaller in the
      innominate artery of the estrogen treated mice, estrogen did not prevent lesion
      progression. Estrogen administration also had no effect on the frequency of intra
      plaque hemorrhage, atrophy of the fibrous cap, medial erosion, and fibro-fatty
      nodules, but did reduce the frequency of fatty streaks that form on top of or
      adjacent to the established lesions in the innominate artery. These data suggest
      that estrogen inhibits the initiation of the fatty streak but does not alter the
      progression of established lesions through stages of instability and healing.

PMID- 12204796
TI  - Potential role of platelet FcgammaRIIA in collagen-mediated platelet activation
      associated with atherothrombosis.
AB  - Collagen-mediated platelet activation contributes significantly to coronary and
      cerebrovascular thrombus formation associated with atherosclerotic plaque
      destabilization. Recent clinical and laboratory observations support a potential
      role for the platelet Fc receptor (FcgammaRIIA) in this process. The purpose of
      this study was to elucidate any association between platelet Fc receptor (FcR)
      expression levels and both atherosclerosis risk factors (ARFs) along with
      collagen-dependent platelet activation. Age and gender-independent variation has
      been described in the expression of this receptor that is stable over time.
      Platelet Fc surface expression was compared between patients experiencing an
      acute coronary or cerebrovascular event, healthy patients with two or more ARFs,
      and healthy patients with fewer than two ARFs. Platelet FcR expression was
      significantly and stably (6-52 weeks, mean 20 weeks) increased in 101 patients
      with acute myocardial infarction, unstable angina, or ischemic stroke syndrome
      (P<0.001) and 38 healthy patients with two or more ARFs (P=0.027) compared with
      109 healthy patients with fewer than two ARFs. Patients with diabetes mellitus
      from all groups had significantly increased platelet FcR expression over those
      without diabetes (P<0.0001). Platelet aggregation studies suggested a correlation
      between number of ARFs per patient, platelet Fc expression levels, and relative
      sensitivity to collagen stimulation. Platelet FcR surface expression is increased
      in patients with an acute coronary or cerebrovascular event, non-acutely ill
      patients with two or more ARFs, and in patients with diabetes mellitus. Increased
      platelet FcR expression may therefore contribute towards risk for
      atherothrombotic events.

PMID- 12204797
TI  - Influence of a glutamate carboxypeptidase II (GCPII) polymorphism (1561C-->T) on
      plasma homocysteine, folate and vitamin B(12) levels and its relationship to
      cardiovascular disease risk.
AB  - Elevated levels of total homocysteine and low folate in blood are independent and
      graded risk factors for arterial occlusive disease. An impairment of folate
      distribution can be an important cause of hyperhomocysteinemia. Glutamate
      carboxypeptidase II (GCPII) regulates the absorption of dietary folates. In the
      present study, we examined the relationship of a 1561C-->T variant in the GCPII
      gene with fasting, post-methionine load plasma homocysteine, folate and vitamin
      B(12) levels and the risk of cardiovascular disease (CVD) in 190 vascular disease
      patients and in 601 apparently healthy controls. Fasting as well as post-load
      homocysteine concentrations associated with the 1561TT genotype tended to be
      lower, whereas the homocysteine concentrations of the 1561CT individuals were not
      different from their 1561CC peers. The 1561C-->T polymorphism significantly
      increased both red blood cell folate and plasma folate concentrations (ANOVA
      P=0.013; test for linear trend P=0.03, respectively), but had no effect on
      vitamin B(12) levels (ANOVA P=0.35). Since not only homocysteine itself is
      considered to be positively associated with the risk of CVD, but also a decreased
      folate status, the results of this study indicate that the 1561C-->T polymorphism
      may affect the predisposition to CVD.

PMID- 12204798
TI  - Serum non-esterified very long-chain PUFA are associated with markers of
      endothelial dysfunction.
AB  - The objective of this study was to investigate the pattern of serum non
      esterified fatty acid (NEFA) fraction in association with atherosclerosis
      development. We have studied possible relationships between eicosapentaenoic acid
      (EPA), docosahexaenoic acid (DHA) and arachidonic acid (AA) in the NEFA fraction
      and biochemical markers of endothelial activation or dysfunction. The study
      population consisted of 152 elderly men with high risk for coronary heart
      disease. The composition of fasting serum NEFA was analysed by gas-liquid
      chromatography. Endothelial activation was evaluated using biochemical analyses
      of some markers of endothelial function. A significant inverse linear association
      was found between serum non-esterified EPA and DHA, and soluble vascular cell
      adhesion molecule-1 (sVCAM-1) (P=0.02 and 0.001, respectively). An inverse linear
      association was found between serum non-esterified AA and sVCAM-1 (P=0.001) and
      von Willebrand Factor (P=0.005). The significant inverse associations for DHA and
      AA were independent from the serum content of other NEFAs. Taken together,
      negative associations were found between sVCAM-1 and the serum levels of non
      esterified DHA, EPA and AA. The inverse relation between the levels of sVCAM-1
      and very long-chain n-3 fatty acids might indicate an anti-inflammatory effect of
      the latter.

PMID- 12204799
TI  - Inverse relationship between total testosterone and anti-oxidized low density
      lipoprotein antibody levels in ageing males.
AB  - Accumulating evidence indicates the involvement of sex hormones in atherogenesis.
      Endogenous testosterone is inversely related to the majority of risk factors for
      atherosclerosis and is known to be a potent immunomodulator. Recently,
      autoantibodies to oxidized LDL (anti-oxLDL Ab) were shown to predict carotid and
      coronary atherosclerosis. The aim of this study was to investigate the
      relationship between these antibodies and testosterone level in ageing males. The
      study group comprised 65 males over 50 years old (42 with coronary artery
      disease). Serum anti-oxLDL Ab titer was measured by enzyme-linked immunoassay and
      total serum testosterone by radioimmunoassay. A significant inverse correlation
      was found between serum anti-oxLDL Ab titer and testosterone concentration (r=
      0.346, P=0.0047). Alteration in serum anti-oxLDL Ab titres showed no correlation
      to classical cardiovascular risk factors, e.g. body mass index, waist/hip ratio,
      smoking, total cholesterol, triglycerides, HDL-cholesterol, LDL-cholesterol. In
      multiple regression analysis only testosterone level was independently associated
      with anti-oxLDL Ab. These data suggest a that fall of testosterone concentration
      in ageing men can influence either oxidative modification of LDL or the immune
      response to these lipoproteins which may be important in the pathogenesis of
      atherosclerosis.

PMID- 12204800
TI  - The Arg allele in position 192 of PON1 is associated with carotid atherosclerosis
      in subjects with elevated HDLs.
AB  - Human serum paraoxonase (PON1) is an HDL-associated enzyme involved in the
      protection of lipoproteins from oxidation. A polymorphism at position 192
      (Gln/Arg) influences its activity in a substrate-dependent manner. The aim of the
      present study was to evaluate, in vivo, the contribution of the PON1-192
      polymorphism to the protective effect of HDLs. Three hundred and forty seven
      subjects in the upper and lower decile of sex-specific HDL cholesterol
      distribution were selected from participants in a cardiovascular disease
      prevention study. PON1 genotypes were determined by PCR amplification and
      restriction analysis. Blood pressure, height, weight, smoking and alcohol habits,
      as well as the presence of familial or personal history of CHD were recorded.
      Plasma lipids and blood glucose were measured by routine enzymatic methods. As a
      measure of antiatherogenic HDL effect, carotid atherosclerosis was assessed by
      ultrasonography. Allele and genotype frequencies did not differ significantly
      between low- and high-HDL groups. Similarly, no significant difference was
      observed among genotypes in all variables studied. Subjects with Gln/Arg or
      Arg/Arg had more carotid abnormalities than Gln/Gln with an adjusted odds ratio
      (OR) of 3.27 (95% CI, 1.61-6.64, P=0.001) for abnormal carotid score. Stepwise
      logistic regression analysis showed that in the whole population age and presence
      of low-HDL were the only independent predictors for abnormal carotid score. In
      low-HDL, age was the only independent predictor entered into the model (OR
      1.09/year, P<0.0001); in high-HDL, age entered first (OR, 1.07/year, P=0.001),
      followed by the presence of Gln/Arg or Arg/Arg (OR, 2.94, 95% CI, 1.47-5.91,
      P=0.002). In conclusion, in subjects with low levels of HDL cholesterol, carotid
      atherosclerosis is not related to PON1-192 polymorphism. On the other hand, in
      subjects with elevated concentration of HDL cholesterol, the presence of carotid
      atherosclerosis is significantly associated with the arginine variant in position
      192 of the PON1 gene.

PMID- 12204801
TI  - Soluble intercellular adhesion molecule-1 is associated with carotid and femoral
      atherosclerosis but not with intima-media thickness in a population-based sample.
AB  - Since inflammatory mechanisms seem to be involved in different stages of
      atherosclerosis, we analysed a random population-based sample of 972 subjects to
      assess the relationships between soluble intercellular adhesion molecule-1 (sICAM
      1), subclinical peripheral atherosclerosis and intima-media thickness (IMT). B
      mode ultrasonography was used to assess the presence of carotid (common and
      internal) and femoral atherosclerotic plaques and to measure common carotid IMT
      (avoiding plaque sites). Mean sICAM-1 level was 287.4 (standard deviation: 102.8)
      and 255.2 (83.5) ng/ml, respectively, in subjects with and without carotid
      plaques (P<0.0001). It equalled 286.7 (101.1) and 249.7 (79.7) ng/ml,
      respectively, in subjects with and without femoral plaques (P<0.0001). Subjects
      beyond the 90th percentile of common carotid IMT had higher sICAM-1 levels than
      those below, but this was not significant (P=0.08). Multiple logistic regression
      analyses adjusted for age, gender and other cardiovascular risk factors showed
      that sICAM-1 was independently associated with the risk of having at least one
      carotid plaque (adjusted odds ratio for a 10 ng/ml increase in sICAM-1: OR=1.03,
      95% confidence interval: [1.02-1.05]) and with the risk of having at least one
      femoral plaque (adjusted OR=1.04 [1.02-1.06]). On the other hand, no significant
      relationship was found in multivariate analysis between sICAM-1 and common
      carotid IMT.

PMID- 12204802
TI  - Atorvastatin lowers lipoprotein(a) but not apolipoprotein(a) fragment levels in
      hypercholesterolemic subjects at high cardiovascular risk.
AB  - The effect of statins on Lp(a) levels is controversial; furthermore, the
      potential action of statins on apo(a) fragmentation is indeterminate. We
      therefore determined the circulating levels of Lp(a) and of apo(a) fragments in
      hypercholesterolemic patients before and after treatment (6 weeks) with
      Atorvastatin 10 mg/day (A10) or Simvastatin 20 mg/day (S20). In a double blind
      study, hypercholesterolemic patients (n=391) at high cardiovascular risk (LDL
      C>=4.13 mmol/l; TG<2.24 mmol/l; 34% with documented CHD; 45% hypertensive; and
      29% current smokers) were assigned to treatment with A10 (n=199) or S20 (n=192).
      Plasma Lp(a) and apo(a) fragment levels (n=206) were measured prior to and after
      treatment. At baseline, A10 and S20 groups did not differ in plasma levels of
      lipids, Lp(a) (A10: 0.45+/-0.48 mg/ml, S20: 0.46+/-0.5), and apo(a) fragments
      (A10: 3.88+/-5.22 microg/ml; S20: 3.25+/-3), and equally in apo(a) isoform size
      (A10: 26+/-5 kr, S20: 25.5+/-5.3). After treatment, both statins significantly
      reduced Lp(a) levels (A10: 0.42+/-0.47 mg/ml, 6% variation, P<0.001; S20: 0.45+/
      0.53 mg/ml, 0.02% variation, P=0.046). A10 and S20 did not significantly differ
      in their efficacy to lower Lp(a) levels. In a multivariate logistic regression
      analysis, the reduction of Lp(a) levels was independently associated with Lp(a)
      baseline concentration, but not to other variables, including LDL-C reduction.
      Plasma levels of apo(a) fragments were not modified by either statin. In
      conclusion, both A10 and S20 significantly lowered Lp(a), although this effect
      was of greater magnitude in atorvastatin-treated patients.

PMID- 12204803
TI  - Chlamydia pneumoniae seropositivity and early carotid atherosclerosis in a
      suburban Japanese population.
AB  - To evaluate the association between Chlamydia pneumoniae (C. pneumoniae)
      infection and carotid atherosclerosis (CA), we investigated CA assessed by
      carotid B-mode ultrasound and known or suspected atherosclerotic risk factors
      including C. pneumoniae IgG and IgA antibodies in 2410 residents (mean age 54.5+/
      13.6 years, 697 men) of a suburban Japanese town. CA was found in 30.1% of men
      and in 14.0% of women, IgG in 59.4% and in 51.4%, and IgA in 36.9% and in 32.4%,
      respectively. In univariate analysis, most conventional atherosclerotic risk
      factors and IgA antibody were significantly associated with CA in both sexes, but
      not IgG. In multivariate logistic regression analysis, independent risk factors
      for CA were confirmed with age and triglycerides (TG) in men and age, systolic
      blood pressure, pack-years of smoking, and low-density lipoprotein cholesterol
      (LDL-C) in women, but not IgG and IgA in either sex. These results do not support
      C. pneumoniae infection as an important risk factor for CA in this Japanese
      population.

PMID- 12204804
TI  - Effects of serum B vitamins on elevated plasma homocysteine levels associated
      with the mutation of methylenetetrahydrofolate reductase gene in Japanese.
AB  - High plasma homocysteine, a risk factor for atherosclerosis, is frequently caused
      by a common mutation in the gene for the enzyme, 5,10-methylenetetrahydrofolate
      reductase (MTHFR), C677T (alanine to valine substitution) or low intake of B
      vitamins that affect the remethylation or transsulfuration pathways in
      homocysteine metabolism. However, the interaction of the C677T mutation and B
      vitamins other than folate has not been well elucidated. We conducted a cross
      sectional survey of 324 men and 641 women who participated in a 1996 health
      examination under a hypothesis that high nutritional status of folate, vitamin
      B12 and vitamin B6 expressed as high serum levels, may compensate for the
      hyperhomocysteinemia associated with homozygosity for the C677T mutation, but not
      for having the mutation per se. Age-adjusted plasma homocysteine levels were
      higher for both men and women with the homozygous genotype for the mutation than
      those who were heterozygous or had no mutation. Elevated homocysteine levels in
      homozygous genotype was attenuated among persons with higher serum levels of
      vitamin B12 and folate, but not vitamin B6, and among persons with the
      combination of lower folate and higher vitamin B12 and of higher folate and
      higher vitamin B12, split by the median. These findings suggest that elevated
      homocysteine levels among Japanese with the homozygous genotype for the MTHFR
      gene mutation can be modified efficiently by dietary supplement of vitamin B12 as
      well as folate.

PMID- 12204805
TI  - Coronary artery calcification is related to functional polymorphism of matrix
      metalloproteinase 3: the Helsinki Sudden Death Study.
AB  - Matrix metalloproteinase 3 (MMP3) is expressed in human coronary atherosclerotic
      lesions and is known to be involved in degradation of the plaque and to be co
      localized with calcium and fibrin deposits in advanced lesions, indicating a
      possible role of MMP3 in arterial calcification. The MMP3 gene promoter
      polymorphism leads to low promoter activity 6A6A, intermediate promoter activity
      5A6A and high promoter activity 5A5A genotypes. To determine whether these
      genotypes predict the extent of atherosclerosis we investigated their association
      with different types of coronary lesions in an autopsy series of 300 middle-aged
      white Finnish men (aged 35-69 years) from the Helsinki Sudden Death Study (HSDS).
      Areas of the coronary wall covered with different atherosclerotic lesions were
      measured and MMP3 genotypes were determined by PCR and minisequencing. In men
      >/=53 years the mean area of calcified lesion in the most severely affected
      coronary artery was significantly associated with the MMP3 genotype (P=0.029).
      Subjects with high promoter activity genotypes had on average larger calcified
      lesion areas than those with the low-activity genotype. The MMP3 genotype
      (P=0.025) persisted as an independent predictor of mean calcified lesion area
      after stepwise adjustment for age, BMI, hypertension, diabetes, number of
      affected vessels and smoking. These data provide evidence that the proposed
      effect of MMP3 in the process of atherogenesis may be modified by the MMP3
      genotype.

PMID- 12204806
TI  - Evidence of insulin resistant lipid metabolism in adipose tissue in familial
      combined hyperlipidemia, but not type 2 diabetes mellitus.
AB  - In patients with familial combined hyperlipidemia (FCHL) and type 2 diabetes
      (DM2) organ-specific differences in insulin resistance may exist. In FCHL and DM2
      in vivo insulin mediated muscle glucose uptake and inhibition of lipolysis were
      studied by euglycemic hyperinsulinemic clamp. Insulin mediated glucose uptake was
      impaired to the same extent in both FCHL and DM2. Only FCHL subjects showed no
      reduction in plasma glycerol concentrations during insulin infusion and
      incomplete suppression of plasma free fatty acid (FFA) concentrations combined.
      This finding indicated that insulin-induced suppression of lipolysis, or
      glycerol/FFA utilization, or both, were impaired in FCHL, in contrast to DM2 or
      control subjects. To analyze these possibilities in more detail, control, FCHL,
      and DM2 adipocytes were studied in vitro. In contrast to adipocytes from DM2 or
      control subjects, no reduction in medium FFA concentration was detected with FCHL
      adipocytes after incubation with insulin. This finding indicated impaired
      intracellular FFA utilization, most likely impaired FFA re-esterification.
      Genetic linkage analysis in 18 Dutch families with FCHL revealed no evidence for
      involvement of LIPE, the hormone sensitive lipase gene, indicating that genetic
      variation in adipocyte lipolysis by LIPE is not the key defect in FCHL. In
      conclusion, FCHL as well as DM2 subjects exhibited in vivo insulin resistance to
      glucose disposal, which occurs mainly in muscle. FCHL subjects showed insulin
      resistant adipose tissue lipid metabolism, in contrast to DM2 and controls. The
      different pattern of organ-specific insulin resistance in FCHL versus DM2
      advances our understanding of differences and similarities in phenotypes between
      these disorders.

PMID- 12204807
TI  - Baseline lipid values partly determine the response to high-dose simvastatin in
      patients with familial hypercholesterolemia. The examination of probands and
      relatives in Statin studies with familial hypercholesterolemia (ExPRESS FH).
AB  - Statins decrease low-density lipoprotein cholesterol (LDL-C), and additionally,
      reduce triglycerides (TG) and raise high-density lipoprotein cholesterol (HDL-C)
      levels. This study evaluated the frequency of abnormal TG and HDL-C levels in
      patients with classical familial hypercholesterolemia (FH) and assessed
      therapeutic response at different baseline levels of these lipoproteins after 1
      year of statin therapy. A total of 508 FH patients were included and mean LDL-C
      levels (8.37+/-2.12 mmol l(-1)) were severely elevated. After a washout period of
      6 weeks, all patients started monotherapy with 80 mg simvastatin. Remarkably, LDL
      C reduction was dependent on baseline LDL-C levels ranging from 51.1 to 45.5% in
      the top versus the bottom third of the LDL-C distribution. Unexpected in FH,
      elevated baseline TG levels were seen in 30% and low HDL-C levels in 15% of all
      patients. Also, changes in these lipoproteins were dependent on baseline levels;
      TG reduction was 40.7 versus 22.2% in patients with elevated versus normal
      levels, while HDL-C increase was 29.1 versus 11.4% in patients with low versus
      normal HDL-C levels. In conclusion, FH patients with the worst lipoprotein
      profile showed the greatest benefit from high-dose simvastatin treatment, since
      changes in these parameters were partly determined by baseline lipid levels.

PMID- 12204808
TI  - C-reactive protein and multiple complex coronary artery plaques in patients with
      primary unstable angina.
AB  - The aim of this study was to investigate the possible association of plasma C
      reactive protein (CRP) levels with the presence of angiographically multiple
      complex lesions (CLs) in patients with primary unstable angina (PUA). For the
      purpose of this study, 228 consecutive patients with PUA who underwent in
      hospital catheterization were evaluated. Plasma CRP levels were measured upon
      patients' admission. Coronary plaques were classified as CL or non-CL according
      to Ambrose's criteria. There were 100 (43.9%) patients with no or one CL (</=1)
      and 128 (56.1%) patients with multiple CLs (>/=2). Tertiles of plasma CRP levels
      upon admission were significantly associated with the number of CLs on
      angiographic studies. In particular there was a significant gradual increase in
      either the number of CLs, or the presence of apparently thrombus-containing CLs
      with increasing of CRP tertiles. By multivariate analysis CRP was independently
      associated with the presence of either multiple CLs (R.R.=1.8, 95%CI=1.5-2.2,
      P<0.001), or angiographically apparent thrombus-containing CLs (R.R.=1.4,
      95%CI=1.2-1.7, P=0.03).High plasma levels of CRP may reflect a multifocal
      activation of the coronary tree in patients with PUA. This finding suggests a
      generalized inflammatory reaction throughout the coronary tree in these patients.

PMID- 12204810
TI  - Predictive value of preprocedural fibrinogen concerning coronary stenting.
AB  - Elevated fibrinogen levels after coronary balloon angioplasty have been reported
      to be useful in predicting restenosis. Therefore, we sought to evaluate the
      relationship between preprocedural fibrinogen levels and the 6-12-month outcomes
      of patients undergoing coronary stenting. Plasma levels of fibrinogen were
      measured in 390 consecutive patients prior to coronary stenting. The primary end
      point was binary restenosis (percent diameter stenosis of >/=50%). The secondary
      combined end point was death due to cardiac causes, myocardial infarction related
      to the target vessel and target lesion revascularization. Patients were grouped
      into tertiles according to fibrinogen levels. Both at baseline and immediately
      after procedure, clinical and angiographic characteristics were almost identical
      in the fibrinogen tertiles. An increase in restenosis rate was observed across
      the tertiles (18.6, 23.9, 38.1%, P<0.001, respectively). In addition, the
      frequency of the secondary end point increased in the highest tertile (14.9,
      21.5, 37.2%, P<0.001, respectively). Multivariate analysis revealed that high
      levels of fibrinogen (per 100 mg/dl, OR 1.82, P<0.001) and stent length (P=0.034)
      were independent predictors for restenosis. An elevated preprocedural fibrinogen
      level should be considered as a stronger predictor for restenosis after coronary
      stenting, which might be associated with coagulation and inflammation.

PMID- 12204809
TI  - Comparing the effects of five different statins on the HDL subpopulation profiles
      of coronary heart disease patients.
AB  - We compared the effects of five different statins (atorvastatin, simvastatin,
      pravastatin, lovastatin, and fluvastatin) on the lipid, lipoprotein, and
      apolipoprotein (apo) A-I-containing high-density lipoprotein (HDL) subpopulation
      profiles of 86 coronary heart disease (CHD) patients. Patients with established
      CHD, and low density lipoprotein (LDL) cholesterol (C)>130 mg/dl, and
      triglyceride (TG)<400 mg/dl, were treated with atorvastatin 20, 40, and 80 mg/day
      and one of the other four statins at 20, 40, and when available 80 mg/day in
      increasing doses (4 weeks of each dose) in a randomized crossover fashion. There
      was an 8-week placebo controlled washout period between different drug
      treatments. All five statins on each dose resulted in significant reductions in
      total- and LDL-C compared to placebo treatment. There were also decreases in
      plasma TG and increases in HDL-C and apoA-I concentrations, but not all
      treatments changed these parameters significantly. Each statin except fluvastatin
      improved the HDL subpopulation profile by increasing the concentrations of the
      large, cholesterol-rich, LpA-I alpha-1 and prealpha-1 HDL subpopulations. CHD
      patients have significantly lower concentration of the large, LpA-I alpha-1 HDL
      particles compared to controls. Our data indicate that statins which are the most
      effective in lowering LDL-C and TG are also the most effective agents in
      modifying the HDL subpopulation profile in CHD patients towards the patterns
      found in healthy individuals. The order of efficacy of statins in increasing
      alpha-1 HDL subpopulation was: atorvastatin, simvastatin, pravastatin, lovastatin
      and fluvastatin.

PMID- 12204811
TI  - Letter in response to recent paper by Fournier et al.

PMID- 12204812
TI  - Treatment of children with familial hypercholesterolemia with colestilan, a newly
      developed bile acid-binding resin.

PMID- 12204813
TI  - Homocysteine and cardiovascular disease in diabetes mellitus.

PMID- 12204814
TI  - Characterization of thrombomodulin gene mutations of the 5'-regulatory region.

PMID- 12204815
TI  - Indicators of ocean health and human health: developing a research and monitoring
      framework.
AB  - We need to critically assess the present quality of the marine ecosystem,
      especially the connection between ecosystem change and threats to human health.
      In this article we review the current state of indicators to link changes in
      marine organisms with eventual effects to human health, identify research
      opportunities in the use of indicators of ocean and human health, and discuss how
      to establish collaborations between national and international governmental and
      private sector groups. We present a synthesis of the present state of
      understanding of the connection between ocean health and human health, a
      discussion of areas where resources are required, and a discussion of critical
      research needs and a template for future work in this field. To understand fully
      the interactions between ocean health and human health, programs should be
      organized around a "models-based" approach focusing on critical themes and
      attributes of marine environmental and public health risks. Given the extent and
      complex nature of ocean and human health issues, a program networking across
      geographic and disciplinary boundaries is essential. The overall goal of this
      approach would be the early detection of potential marine-based contaminants, the
      protection of marine ecosystems, the prevention of associated human illness, and
      by implication, the development of products to enhance human well-being. The
      tight connection between research and monitoring is essential to develop such an
      indicator-based effort.

PMID- 12204816
TI  - Can environmental purchasing reduce mercury in U.S. health care?
AB  - Environmental purchasing represents an innovative approach to mercury control for
      the health care sector in the United States. The U.S. health care sector creates
      significant environmental impacts, including the release of toxic substances such
      as mercury. Our goal in this study was to provide the health care industry with a
      method of identifying the environmental impacts associated with the products they
      use. The Health Care Environmental Purchasing Tool (HCEPT) was developed and
      tested at nine health care facilities in the Great Lakes region of the United
      States. As a result, more than 1 kg of mercury was removed from four facilities.
      The complexity of the supply chain inhibits a direct environmental information
      exchange between health-care decision makers and suppliers. However, a dialogue
      is starting within the health care supply chain to address environmental issues.
      The HCEPT has been shown to assist health care facilities with that dialogue by
      identifying products that have environmental consequences. This promising tool is
      now available for further experimentation and modification, to facilitate overall
      environmental improvement, and to provide a systematic method for environmental
      assessment of health care products.

PMID- 12204817
TI  - Linking dioxins to diabetes: epidemiology and biologic plausibility.
AB  - Recent epidemiologic studies suggest a possible association between dioxin-like
      compounds (DLCs) and diabetes in human populations, although experimental links
      between DLCs and diabetes are lacking. The public health significance of such an
      association is that all populations are exposed to small but measurable levels of
      DLCs, chronic low-dose exposure to which may hasten the onset of adult-onset
      diabetes in susceptible individuals. In this article, we review the epidemiologic
      studies and propose biologically plausible connections between dioxins and
      diabetes. Specifically, we suggest that aryl hydrocarbon (Ah) receptor functions
      may antagonize peroxisome proliferator-activated receptor (PPAR) functions, and
      hence that the Ah receptor may promote diabetogenesis through a mechanism of PPAR
      antagonism.

PMID- 12204818
TI  - The effect of weather on respiratory and cardiovascular deaths in 12 U.S. cities.
AB  - We carried out time-series analyses in 12 U.S. cities to estimate both the acute
      effects and the lagged influence of weather on respiratory and cardiovascular
      disease (CVD) deaths. We fit generalized additive Poisson regressions for each
      city using nonparametric smooth functions to control for long time trend, season,
      and barometric pressure. We also controlled for day of the week. We estimated the
      effect and the lag structure of both temperature and humidity based on a
      distributed lag model. In cold cities, both high and low temperatures were
      associated with increased CVD deaths. In general, the effect of cold temperatures
      persisted for days, whereas the effect of high temperatures was restricted to the
      day of the death or the day before. For myocardial infarctions (MI), the effect
      of hot days was twice as large as the cold-day effect, whereas for all CVD deaths
      the hot-day effect was five times smaller than the cold-day effect. The effect of
      hot days included some harvesting, because we observed a deficit of deaths a few
      days later, which we did not observe for the cold-day effect. In hot cities,
      neither hot nor cold temperatures had much effect on CVD or pneumonia deaths.
      However, for MI and chronic obstructive pulmonary disease deaths, we observed
      lagged effects of hot temperatures (lags 4-6 and lags 3 and 4, respectively). We
      saw no clear pattern for the effect of humidity. In hierarchical models, greater
      variance of summer and winter temperature was associated with larger effects for
      hot and cold days, respectively, on respiratory deaths.

PMID- 12204819
TI  - AP-1, NF-kappa-B, and ERK activation thresholds for promotion of neoplastic
      transformation in the mouse epidermal JB6 model.
AB  - The promotion-sensitive mouse epidermal JB6 cells (clone 41) have been used to
      identify the tumor-promoting activity of various compounds. Because treatment by
      tumor promoters [12-O-tetradecanoylphorbol-13-acetate (TPA), epidermal growth
      factor (EGF), or tumor necrosis factor alpha (TNF-alpha)] transforms clone 41
      cells to anchorage-independent and tumorigenic phenotypes, they are considered to
      be undergoing late-stage tumor promotion. Here we address the question of how
      much activation of transformation-relevant transcription factors [activator
      protein-1 (AP-1), ternary complex factors (TCFs), or nuclear factor kappa-B (NF
      kappa-B)] is required for transformation response and how much tumor promoter
      produces significant risk of transformation. Stable transfectants harboring a
      reporter construct with an AP-1 response element, serum-response element (SRE),
      or NF-kappa-B response element were established. We examined the relationship
      between concentration of tumor promoters, key signaling events, and activation of
      the transcription factors. A concentration of > 0.2 nM TPA or 0.12 ng/mL (0.02
      nM) EGF produced a significant increase in transformation response as well as in
      extracellular signal-regulated protein kinase (ERK), SRE, or AP-1 activation.
      Treatment with > 0.4 U/mL (2.35 pM) TNF-alpha increased NF-kappa-B activity and
      transformation response in a dose-dependent manner. However, transformation
      response decreased at > 33 U/mL TNF-alpha due to a cytotoxic response. These
      findings suggest that the signaling pathway leading to the activation of ERK,
      TCF, and AP-1 proteins constitutes a major factor determining the risk of tumor
      promotion by TPA or EGF. Cell toxicity in addition to NF-kappa-B activation
      should be considered in predicting TNF-alpha-induced transformation response.

PMID- 12204820
TI  - Long-term, low-dose lead exposure alters the gonadotropin-releasing hormone
      system in the male rat.
AB  - Lead is a male reproductive toxicant. Data suggest that rats dosed with
      relatively high levels of lead acetate for short periods of time induced changes
      in the hypothalamic gonadotropin-releasing hormone (GnRH) at the molecular level,
      but these changes were attenuated with increased concentration of exposure. The
      current study evaluated whether exposure to low levels of lead acetate over
      longer periods of time would produce a similar pattern of adaptation to toxicity
      at the molecular and biologic levels. Adult 100-day-old Sprague-Dawley male rats
      were dosed with 0, 0.025, 0.05, 0.1, and 0.3% lead acetate in water. Animals were
      killed after 1, 4, 8, and 16 weeks of treatment. Luteinzing hormone (LH) and GnRH
      levels were measured in serum, and lead levels were quantified in whole blood.
      Hypothalamic GnRH mRNA levels were also quantified. We found no significant
      differences in serum LH and GnRH among the groups of animals treated within each
      time period. A significant dose-related increase of GnRH mRNA concentrations with
      lead dosing occurred in animals treated for 1 week. Animals treated for more than
      1 week also exhibited a significant increase in GnRH mRNA, but with an
      attenuation of the increase at the higher concentrations of lead with increased
      duration of exposure. We conclude that the signals within and between the
      hypothalamus and pituitary gland appear to be disrupted by long-term, low-dose
      lead exposure.

PMID- 12204821
TI  - The association of particulate air metal concentrations with heart rate
      variability.
AB  - Numerous studies show an association between particulate air pollution and
      adverse health effects. Particulate matter is a complex mixture of elemental
      carbon, ammonium, sulfates, nitrates, organic components, and metals. The
      mechanisms of action of particulate matter less than or equal to 2.5 micro m in
      mean aerodynamic diameter (PM(2.5)), as well as the constituents responsible for
      the observed cardiopulmonary health effects, have not been identified. In this
      study we focused on the association between the metallic component of PM(2.5) and
      cardiac autonomic function based on standard heart rate variability (HRV)
      measures in an epidemiologic study of boilermakers. Thirty-nine male boilermakers
      were monitored throughout a work shift. Each subject wore an ambulatory
      electrocardiogram (Holter) monitor and a personal monitor to measure PM(2.5). We
      used mixed-effects models to regress heart rate and SDNN index (standard
      deviation of the normal-to-normal) on PM(2.5) and six metals (vanadium, nickel,
      chromium, lead, copper, and manganese). There were statistically significant mean
      increases in the SDNN index of 11.30 msec and 3.98 msec for every 1 micro g/m(3)
      increase in the lead and vanadium concentrations, respectively, after adjusting
      for mean heart rate, age, and smoking status. Small changes in mean heart rate
      were seen with all exposure metrics. The results of this study suggest an
      association between exposure to airborne metals and significant alterations in
      cardiac autonomic function. These results extend our understanding of the adverse
      health effects of the metals component of ambient PM(2.5).

PMID- 12204822
TI  - Y-chromosomal DNA markers for discrimination of chemical substance and effluent
      effects on sexual differentiation in salmon.
AB  - Chinook salmon alevins were exposed during their labile period for sex
      differentiation to different concentrations of bleached kraft mill effluent
      (BKME), primary sewage effluent, secondary sewage effluent (SE), 17ss-estradiol,
      testosterone, and nonylphenol. After exposure for 29 days post hatching (DPH),
      fish were allowed to grow until 103 and 179 DPH, at which time their genetic sex
      was determined using Y-chromosomal DNA markers and their gonadal sex was
      determined by histology. Independent of treatment, all fish identified as genetic
      females (XX) in these experiments possessed normal female gonads. Only the
      highest dose of some treatments affected the development of gonads in genetic XY
      males. At 103 DPH, some genetic males treated with 1 micro g estradiol/L, BKME
      100%,and SE 30% developed as physiological females, presenting ovaries identical
      to genetic females in the control group. The physiological female condition in XY
      fish was also observed in these treatments groups at 179 DPH, which suggests that
      the effect is permanent, whereas in other groups the effect changed between
      sampling periods. Identification of the genetic sex of individual animals using
      sex-linked DNA markers provides a useful tool for investigating environmental
      factors influencing sex determination and differentiation.

PMID- 12204823
TI  - Comparison of home lead dust reduction techniques on hard surfaces: the New
      Jersey assessment of cleaning techniques trial.
AB  - High efficiency particulate air filter (HEPA) vacuums, which collect particles >
      0.3 micro m, and trisodium phosphate (TSP), a detergent claimed to selectively
      remove lead, have been included in the HUD Guidelines for the Evaluation and
      Control of Lead Based Paint Hazards in Housing without systematic validation of
      their effectiveness. At the time the study was initiated, both HEPA vacuums and
      TSP were relatively expensive, they were not readily found in urban retail
      centers, and there were environmental concerns about the use and disposal of high
      phosphate detergents. A randomized, controlled trial was conducted in urban high
      risk homes in northern New Jersey to determine whether a more readily available
      and less expensive low-phosphate, non-TSP detergent and non-HEPA vacuum could
      perform as well as TSP and a HEPA vacuum in a cleaning protocol. Homes were
      randomized to one of three cleaning methods: TSP/HEPA vacuum, TSP/non-HEPA
      vacuum, or non-TSP/non-HEPA vacuum. Change in log-transformed lead loading was
      used in mixed models to compare the efficacy of the three cleaning techniques
      separately for uncarpeted floors, window sills, and window troughs. After we
      adjusted for baseline lead loading, the non-HEPA vacuum produced larger
      reductions on hard floors [19%; 95% confidence interval (CI), 3-38%], but the
      HEPA vacuum produced larger reductions on window sills (22%; 95% CI, 11-32%) and
      larger reductions on window troughs (16%; 95% CI, -4 to 33%). The non-TSP
      produced larger reductions on window troughs (21%; 95% CI, -2 to 50%), but TSP
      produced larger reductions on hard floors (5%; 95% CI, -12 to 19%) and window
      sills (8%; 95% CI, -5 to 20%). TSP/HEPA produced larger reductions on window
      sills (28%; 95% CI, 18-37%) and larger reductions on window troughs (2%; 95% CI, 
      24 to 23%), whereas the non-TSP/non-HEPA method produced larger reductions on
      hard floors (13%; 95% CI, -5 to 34%). Because neither vacuum nor detergent
      produced consistent results across surface types, the use of low-phosphate
      detergents and non-HEPA vacuums in a temporary control measure is supported.

PMID- 12204824
TI  - Hydroxylated PCB metabolites and PCBs in serum from pregnant Faroese women.
AB  - In the Faroe Islands in the North Atlantic, the traditional diet includes pilot
      whale meat and blubber and other marine food. Fatty fish and blubber of mammals
      may contain high concentrations of organohalogen substances (OHSs). Elevated
      levels of OHSs have been reported from the Faroe Islands, first documented in
      breast milk samples obtained in 1987. The aim of this study was to determine the
      concentrations of hydroxylated polychlorinated biphenyls (OH-PCBs) and
      polychlorinated biphenyls (PCBs) in serum samples from pregnant Faroese women
      known to differ in their dietary habits. High concentrations of OH-PCBs and PCBs
      were found in part of the human serum samples analyzed, and the relative OH-PCB
      and PCB congener distributions were similar to those observed elsewhere. There
      was a wide span between the lowest and highest OH-PCB and PCB concentrations in
      the serum samples analyzed, with ranges of 19-1,800 ng/g lipid weight (lw) and
      150-22,000 ng/g lw, respectively. The ratio of sigmaOH-PCB/sigmaPCB averaged
      about 10% and varied little. 4-Hydroxy-2,2,3,4,5,5,6-heptachlorobiphenyl was the
      most abundant OH-PCB metabolite in all samples analyzed, with four other OH-PCB
      congeners as dominating metabolites in the serum. More than 25 additional OH-PCBs
      were indicated. This study confirms the presence of high concentrations of
      organohalogen substances in populations or areas far removed from their sources.

PMID- 12204826
TI  - Disease transmission models for public health decision making: toward an approach
      for designing intervention strategies for Schistosomiasis japonica.
AB  - Mathematical models of disease transmission processes can serve as platforms for
      integration of diverse data, including site-specific information, for the purpose
      of designing strategies for minimizing transmission. A model describing the
      transmission of schistosomiasis is adapted to incorporate field data typically
      developed in disease control efforts in the mountainous regions of Sichuan
      Province in China, with the object of exploring the feasibility of model-based
      control strategies. The model is studied using computer simulation methods.
      Mechanistically based models of this sort typically have a large number of
      parameters that pose challenges in reducing parametric uncertainty to levels that
      will produce predictions sufficiently precise to discriminate among competing
      control options. We describe here an approach to parameter estimation that uses a
      recently developed statistical procedure called Bayesian melding to sequentially
      reduce parametric uncertainty as field data are accumulated over several seasons.
      Preliminary results of applying the approach to a historical data set in
      southwestern Sichuan are promising. Moreover, technologic advances using the
      global positioning system, remote sensing, and geographic information systems
      promise cost-effective improvements in the nature and quality of field data.
      This, in turn, suggests that the utility of the modeling approach will increase
      over time.

PMID- 12204825
TI  - Effects of hexamethylene diisocyanate exposure on human airway epithelial cells:
      in vitro cellular and molecular studies.
AB  - In this study we developed an in vitro exposure model to investigate the effects
      of hexamethylene diisocyanate (HDI) on human airway epithelial cells at the
      cellular and molecular level. We used immunofluorescence analysis (IFA) to
      visualize the binding and uptake of HDI by airway epithelial cell lines (A549 and
      NCI-NCI-H292) and microarray technology to identify HDI sensitive genes. By IFA,
      we observed that subcytotoxic concentrations of HDI form microscopic micelles
      that appear to be taken up by cells over a 3-hr period postexposure. Microarray
      analysis (4.6K genes) of parallel cultures identified four genes (thioredoxin
      reductase, dihydrodiol dehydrogenase, TG interacting factor, and stanniocalcin)
      whose mRNA levels were up-regulated after HDI exposure. Northern analysis was
      used to confirm that HDI increased message levels of these four genes and to
      further explore the dose dependence and kinetics of the response. The finding
      that HDI exposure increases thioredoxin reductase expression supports previous
      studies suggesting that HDI alters thiol-redox homeostasis, an important sensor
      of cellular stress. Another of the HDI-increased genes, a dihydrodiol
      dehydrogenase, encodes a protein previously shown to be specifically susceptible
      to HDI conjugation, and known to detoxify other hydrocarbons. Together, the data
      describe a novel approach for investigating the effects of HDI binding and uptake
      by human airway epithelial cells and begin to identify genes that may be involved
      in the acute response to exposure.

PMID- 12204827
TI  - Combining xenoestrogens at levels below individual no-observed-effect
      concentrations dramatically enhances steroid hormone action.
AB  - The low potency of many man-made estrogenic chemicals, so-called xenoestrogens,
      has been used to suggest that risks arising from exposure to individual chemicals
      are negligible. Another argument used to dismiss concerns of health effects is
      that endogenous steroidal estrogens are too potent for xenoestrogens to
      contribute significantly to estrogenic effects. Using a yeast reporter gene assay
      with the human estrogen receptoralpha, we tested these ideas experimentally by
      assessing the ability of a combination of 11 xenoestrogens to affect the actions
      of 17ss-estradiol. Significantly, each xenoestrogen was present at a level well
      below its no-observed-effect concentration (NOEC). To derive accurate
      descriptions of low effects, we recorded concentration-response relationships for
      each xenoestrogen and for 17ss-estradiol. We used these data to predict entire
      concentration-response curves of mixtures of xenoestrogens with 17ss-estradiol,
      assuming additive combination effects. Over a large range of concentrations, the
      experimentally observed responses decisively confirmed the model predictions. The
      combined additive effect of the 11 xenoestrogens led to a dramatic enhancement of
      the hormone's action, even when each single agent was present below its NOEC. Our
      results show that not even sub-NOEC levels of xenoestrogens can be considered to
      be without effect on potent steroidal estrogens when they act in concert with a
      large number of similarly acting chemicals. It remains to be seen to what degree
      these effects can be neutralized by environmental chemicals with antiestrogenic
      activity. Nevertheless, potential human and wildlife responses induced by
      additive combination effects of xenoestrogens deserve serious consideration.

PMID- 12204828
TI  - Effect of nickel sulfate on testicular steroidogenesis in rats during protein
      restriction.
AB  - Nickel, a widely used heavy metal, exerts potent toxic effects on peripheral
      tissues as well as on the reproductive system. Low dietary protein coupled with
      exposure to this metal induces more severe changes, including biochemical
      defects, structural disorders, and altered physiologic functions. This study was
      designed to assess the effects of nickel sulfate on testicular steroidogenesis
      and to ascertain whether such alterations are reversible with normal protein and
      protein-restricted dietary regime. Nickel sulfate [2 mg/100 g body weight (bw)]
      dissolved in double-distilled water was administered on alternate days for 10
      doses in a normal protein diet (18% casein) and a protein-restricted diet (5%
      casein) to Wistar male albino rats (bw 160 +/- 5 g). Two groups, one with a
      normal protein diet and the other with a protein-restricted diet, served as
      controls. Twenty-four hours after the last treatment, all the animals except
      those in withdrawal groups were sacrificed by decapitation. We observed a
      significant reduction in the activities of the testicular steroidogenic enzymes
      and plasma testosterone concentration accompanied by a significant elevation in
      cholesterol and ascorbic acid level in both dietary groups. After 15 days of
      withdrawal from the nickel sulfate treatment, the testicular steroidogenic
      enzymes, along with plasma testosterone level, improved significantly in both
      normal protein-fed and protein-restricted dietary groups. The effects of nickel
      on testicular cholesterol and ascorbic acid concentration were also reduced after
      withdrawal. Our results indicate that nickel sulfate affects the steroidogenic
      enzymes, causing alteration in the formation of testosterone in both dietary
      groups, which was manifested in the elevated cholesterol and ascorbic acid level
      with decreased activities of steroidogenic enzymes in adult rats testes. However,
      these alterations were reversible in both groups of animals fed normal protein
      diets and protein-restricted diets.

PMID- 12204829
TI  - Health effects assessment for environmental perchlorate contamination: the dose
      response for inhibition of thyroidal radioiodine uptake in humans.
AB  - Application of a sensitive new detection method has revealed widespread
      perchlorate contamination of groundwater in the southwestern United States,
      typically at 0.005-0.020 mg/L (5-20 ppb). Perchlorate is a competitive inhibitor
      of the process by which iodide is actively transported from the bloodstream into
      the thyroid. This inhibitory action of perchlorate is the basis of its
      pharmaceutical use (in the treatment of hyperthyroidism) as well as its potential
      toxicity. To establish the dose response in humans for perchlorate inhibition of
      thyroidal iodide uptake and any short-term effects on thyroid hormones, we gave
      perchlorate in drinking water at 0.007, 0.02, 0.1, or 0.5 mg/kg-day to 37 male
      and female volunteers for 14 days. In 24 subjects we performed 8- and 24-hr
      measurements of thyroidal (123)I uptake (RAIU) before exposure, on exposure days
      2 (E2) and 14 (E14), and 15 days postexposure (P15). In another 13 subjects we
      omitted both E2 studies and the 8-hr P15 study. We observed a strong correlation
      between the 8- and 24-hr RAIU over all dose groups and measurement days. We found
      no difference between E2 and E14 in the inhibition of RAIU produced by a given
      perchlorate dose. We also found no sex difference. On both E2 and E14, the dose
      response was a negative linear function of the logarithm of dose. Based on the
      dose response for inhibition of the 8- and 24-hr RAIU on E14 in all subjects, we
      derived estimates of the true no-effect level: 5.2 and 6.4 micro g/kg-day,
      respectively. Given default body weight and exposure assumptions, these doses
      would be ingested by an adult if the drinking-water supply contained perchlorate
      at concentrations of approximately 180 and 220 micro g/L (ppb), respectively. On
      P15, RAIU was not significantly different from baseline. In 24 subjects we
      measured serum levels of thyroxine (total and free), triiodothyronine, and
      thyrotropin in blood sampled 16 times throughout the study. Only the 0.5 mg/kg
      day dose group showed any effect on serum hormones: a slight downward trend in
      thyrotropin levels in morning blood draws during perchlorate exposure, with
      recovery by P15.

PMID- 12204831
TI  - Mapping for prevention: GIS models for directing childhood lead poisoning
      prevention programs.
AB  - Environmental threats to children's health--especially low-level lead exposure-
      are complex and multifaceted; consequently, mitigation of these threats has
      proven costly and insufficient and has produced economic and racial disparities
      in exposure among populations. Policy makers, public health officials, child
      advocates, and others currently lack the appropriate infrastructure to evaluate
      children's risk and exposure potential across a broad range of risks. Unable to
      identify where the highest risk of exposure occurs, children's environmental
      health programs remain mitigative instead of preventive. In this article we use
      geographic information system spatial analysis of data from blood lead screening,
      county tax assessors, and the U.S. Census to predict statistically based lead
      exposure risk levels mapped at the individual tax parcel unit in six counties in
      North Carolina. The resulting model uses weighted risk factors to spatially
      locate modeled exposure zones, thus highlighting critical areas for targeted
      intervention. The methods presented here hold promise for application and
      extension to the other 94 North Carolina counties and nationally, as well as to
      other environmental health risks.

PMID- 12204830
TI  - Home and allergic characteristics of children with asthma in seven U.S. urban
      communities and design of an environmental intervention: the Inner-City Asthma
      Study.
AB  - Most published environmental remediation interventions have been directed at
      single allergens and have employed demanding strategies; few have been performed
      in the homes of inner-city children disproportionately burdened by asthma. Our
      objective was a) to describe the allergen sensitivities, environmental tobacco
      smoke (ETS) exposure, and home environmental characteristics of a national sample
      of inner-city children with moderate to severe asthma and b) to develop and
      implement a multifaceted, home-based comprehensive intervention to reduce home
      allergens and ETS, tailored to the specific sensitization and exposure profiles
      of those children. Allergen skin testing and a home evaluation were performed to
      determine the presence of ETS and factors known to be associated with increased
      indoor allergen levels. Based on published remediation techniques, a home
      environmental intervention, organized into modules, each addressing one of five
      specific allergen groups or ETS, was designed. Of 994 allergic children from
      seven U.S. urban communities, 937 successfully completed baseline interviews and
      home allergen surveys and were enrolled. More than 50% of children had positive
      skin tests to three or more allergen groups. Cockroaches were reported in 58% of
      homes, wall-to-wall carpeting in the child's bedroom in 55%, a smoker in 48%,
      mice or rats in 40%, and furry pets in 28%. More than 60% of enrolled families
      received four or more modules, and between 94% and 98% of all modules were
      completed. We conclude that most inner-city children with moderate to severe
      asthma are sensitized to multiple indoor allergens and that environmental factors
      known to be associated with asthma severity are commonly present in their homes.
      The intervention developed for the Inner-City Asthma Study employs accepted
      methods to address an array of allergens and ETS exposure while ensuring that the
      intervention is tailored to the specific sensitization profiles and home
      characteristics of these children.

PMID- 12204832
TI  - Critical windows of exposure to household pesticides and risk of childhood
      leukemia.
AB  - The potential etiologic role of household pesticide exposures was examined in the
      Northern California Childhood Leukemia Study. A total of 162 patients (0-14 years
      old) with newly diagnosed leukemia were rapidly ascertained during 1995-1999, and
      162 matched control subjects were randomly selected from the birth registry. The
      use of professional pest control services at any time from 1 year before birth to
      3 years after was associated with a significantly increased risk of childhood
      leukemia [odds ratio (OR) = 2.8; 95% confidence interval (CI), 1.4-5.7], and the
      exposure during year 2 was associated with the highest risk (OR = 3.6; 95% CI,
      1.6-8.3). The ORs for exposure to insecticides during the 3 months before
      pregnancy, pregnancy, and years 1, 2, and 3 were 1.8 (95% CI, 1.1-3.1), 2.1 (95%
      CI, 1.3-3.5), 1.7 (95% CI, 1.0-2.9), 1.6 (95% CI, 1.0-2.7), and 1.2 (95% CI, 0.7
      2.1), respectively. Insecticide exposures early in life appear to be more
      significant than later exposures, and the highest risk was observed for exposure
      during pregnancy. Additionally, more frequent exposure to insecticides was
      associated with a higher risk. In contrast to insecticides, the association
      between herbicides and leukemia was weak and nonsignificant. Pesticides were also
      grouped based on where they were applied. Exposure to indoor pesticides was
      associated with an increased risk, whereas no significant association was
      observed for exposure to outdoor pesticides. The findings suggest that exposure
      to household pesticides is associated with an elevated risk of childhood leukemia
      and further indicate the importance of the timing and location of exposure.

PMID- 12204833
TI  - Children's respiratory morbidity prevalence in relation to air pollution in four
      Chinese cities.
AB  - We examined respiratory health effects of long-term exposure to ambient air
      pollution in 7,621 schoolchildren residing in eight districts of four Chinese
      cities. The four cities exhibited wide between-city and within-city gradients in
      ambient levels of four size fractions of particulate matter [less than or equal
      to 2.5 micro m in aerodynamic diameter (PM(2.5)), between 2.5 and 10 micro m
      (PM(10-2.5)), less than or equal to 10 micro m (PM(10)), and total suspended
      particulates (TSP)] and two gaseous pollutants (SO(2) and NO(x)). Informed
      consent and written responses to questionnaires about children's personal,
      residential, and family information, as well as their health histories and
      status, were obtained with the help of the parents and the school personnel. We
      used a two-stage regression approach in data analyses. In the first-stage
      logistic regressions, we obtained logits of district-specific prevalence of
      wheeze, asthma, bronchitis, hospitalization for respiratory diseases, persistent
      cough, and persistent phlegm, adjusted for covariates representing personal,
      household, and family parameters. Some of these covariates were found to be risk
      factors of children's respiratory health, including being younger in the study
      group, being male, having been breast-fed, sharing bedrooms, sharing beds, room
      being smoky during cooking, eye irritation during cooking, parental smoking, and
      a history of parental asthma. In several of the second-stage variance-weighted
      linear regressions, we examined associations between district-specific adjusted
      prevalence rates and district-specific ambient levels of each pollutant. We found
      positive associations between morbidity prevalence and outdoor levels of PM of
      all size fractions, but the association appeared to be stronger for coarse
      particles (PM(10-2.5)). The results also present some evidence that ambient
      levels of NO(x) and SO(2) were positively associated with children's respiratory
      symptoms, but the evidence for these two gaseous pollutants appeared to be weaker
      than that for the PM.

PMID- 12204834
TI  - Geologic environments and health in China.

PMID- 12204835
TI  - Parental exposure to dioxin and offspring sex ratios.

PMID- 12204836
TI  - Reviving China's ruined rivers.

PMID- 12204837
TI  - Taking a world view of asthma.

PMID- 12204838
TI  - Economy and environment: China seeks a balance.

PMID- 12204839
TI  - China: the next environmental super power?

PMID- 12204840
TI  - Mighty mica: synthetic clay remediates radium.

PMID- 12204841
TI  - Predictors of treatment failure during highly active antiretroviral therapy
      (racing trial).
AB  - PURPOSE: To determine factors associated with virological failure during long
      term treatment with the triple combination of saquinavir soft gel capsule,
      zalcitabine and zidovudine. METHOD: Open-label, prospective, multicentre study
      undertaken in private practices and the outpatient department of the Auguste
      Viktoria-Hospital. A total of 95 patients with plasma HIV RNA > 5000 copies/ml
      who had received no more than 6 months pre-treatment with NRTIs and no prior PI
      therapy received saquinavir soft gel, zalcitabine and zidovudine for 52 weeks,
      before being randomly assigned to either remain on therapy or switch to
      nelfinavir, lamivudine and zidovudine for further 52 weeks. RESULTS: Combination
      therapy with saquinavir, zalcitabine and zidovudine was found to be effective and
      well tolerated, with virological response to therapy maintained for up to 2
      years. In patients responding to therapy, switching to a novel triple regimen did
      not result in a virological or immunological worsening, but it did not confer an
      additional clinical benefit. Factors predictive of early treatment failure
      (virological failure within 16 weeks of treatment initiation) included high viral
      load and presence of RT mutations at baseline (OR: 0.30, 95% CI 0.11 0.83 and OR
      0.13, 95% CI 0.03 0.52, respectively), with baseline viral load and the
      development of genotypic mutations on therapy being predictive of late treatment
      failure (16 52 weeks; OR: 0.15, 95% 0.05 0.46 and OR: 0.26, 95% CI < 0.001 1.16,
      respectively). Plasma saquinavir concentration < 50 mg/ml at 4 weeks was also
      found to be an independent risk factor for both early and late treatment failure
      (OR: 1.80, 95% CI 1.23 2.64 and OR: 1.16, 95% CI 0.84 1.60, respectively).
      CONCLUSIONS: While antiretroviral drug resistance appears to be a principal cause
      of treatment failure, other factors such as inadequate drug plasma concentrations
      also play a role.

PMID- 12204842
TI  - Quantification of total abdominal fat volumes using magnetic resonance imaging.
AB  - The purpose of this study was to develop a rapid and reliable method for the
      measurement of total abdominal fat volumes in diabetic patients using magnetic
      resonance imaging (MRI). Total volume coverage of the abdomen was obtained using
      T1-weighted images in 37 diabetic patients (age 48 +/- 13 y mean +/-SD).
      Quantification of intraabdominal (IAF), subcutaneous (SCF), and total abdominal
      fat volumes (TAF) was performed using a semiautomated computer assisted analysis.
      The variability of image analysis for fat measurements between two observers and
      within observers was assessed. Mean volumes (+/- SD) for IAF, SCF and TAF were
      10.5 l (+/- 5.0 l), 15.1 l (+/-7.3 l) and 25.7 l (+/-11.5 l), respectively.
      Reliability of measurements was excellent for both observers (observer I:
      intraobserver reliability IAF, SCF and TAF: r = 0.999, r = 0.999 r = 1.0,
      observer II: r = 0.999, r = 0.999 and r = 1.0), as well as between both observers
      (interobserver reliability IAF, SCF, and TAF: r = 0.999, r = 0.999, r = 1.0). A
      single computer analysis required about 9 min in addition to 7 min scan time. The
      developed analysis method of MR images allows a rapid and reliable determination
      of total intraabdominal, subcutaneous and total fat volumes. This method has the
      potential to be very valuable in respective studies in patients with diabetes.

PMID- 12204843
TI  - Exhaled hydrogen peroxide, nitrite and nitric oxide in healthy children: decrease
      of hydrogen peroxide by atmospheric nitric oxide.
AB  - Hydrogen peroxide (H2O2) and nitrite (NO2-) in exhaled breath condensate have
      recently been suggested as non-invasive markers of airway inflammation. The goal
      of this study was to clarify the role of factors that may potentially influence
      the measurement of H2O2 and nitrite and to look for possible correlations among
      these inflammatory markers. H2O2 and nitrite values were assessed
      fluorometrically in breath condensate of 102 healthy children (age 4-18 years)
      and a detailed status of atopy (including history, lung function and skin prick
      test) was taken in all children. To find out the role of atmospheric nitric
      oxide, eNO and envNO were measured via chemiluminescence in association with the
      sampling of the breath condensate. Median (interquartile range) H2O2 was 0.51
      (0.26 - 0.74) microM and nitrite was 3.3 (2.7 4.1) microM. A significant negative
      correlation between H2O2 and envNO was observed (r = -0.50; p < 0.0001). ENO was
      independent of envNO at our envNO range up to 56 ppb. No further correlation was
      found. The inflammatory markers in exhaled breath condensate H2O2, nitrite and
      eNO are not interrelated to each other in healthy children. Whereas eNO was not
      dependent on envNO values, high envNO values must be taken into account when
      measuring H2O2 in exhaled breath condensate.

PMID- 12204844
TI  - Induction of antibodies to viscotoxins A1, A2, A3, and B in tumour patients
      during therapy with an aqueous mistletoe extract.
AB  - Mistletoe extracts exert immunomodulatory properties on immunocompetent cells of
      the innate as well as the specific immune system. These effects have been mainly
      ascribed to mistletoe lectin 1 (ML-1) present in most of the extracts. However,
      it became evident that also other components of these extracts may induce
      immunological reactions, and especially viscotoxins (VT) may be of relevance. Aim
      of the study was, therefore, to evaluate whether VT like ML-1 could activate B
      cells and lead to the production of VT-specific antibodies. Sera from 26 patients
      with different tumours who were treated with the mistletoe extract ABNOBAviscum
      Mali (AM) 4 for at least 18 weeks were analysed before therapy and after 3, 6, 9,
      12, and 18 weeks. Sera were tested by ELISA against the four viscotoxins A1, A2,
      A3, B, as well as against ML-1. Within the observation period twenty-four (92%)
      of the 26 patients developed antibodies to at least one of the four VT and 25
      (96%) to ML-1. In most instances, anti-VT antibodies appeared after 6-9 weeks of
      treatment. The antibodies were predominantly of the IgG type belonging
      preferentially to the IgG1 and IgG3 subclass. IgE antibodies were found only to
      VT-B and to ML-1. There was no relation between the development of antibodies to
      VT and ML-1, and also cross-reactivity could be excluded with high probability.
      These data indicate that not only ML-1 but also VT induce immunological responses
      in patients treated with mistletoe extracts. Whether there is any relationship to
      the postulated anti-tumour effect of mistletoe extracts has, however, still to be
      evaluated.

PMID- 12204845
TI  - Regular intake of non-opioid analgesics is associated with an increased risk of
      restless legs syndrome in patients maintained on antidepressants.
AB  - OBJECTIVE: To evaluate prevalence and risk factors of restless legs syndrome
      (RLS) in secondary-care patients maintained on tricyclic and serotonin reuptake
      inhibiting antidepressants. METHOD: A total of 243 subjects with affective and
      anxiety disorders were interviewed for symptoms of RLS before and after at least
      6 months of antidepressant pharmacotherapy within a naturalistic study. Logistic
      regression analysis was applied to adjust for the effects of age, gender,
      comorbidities, and the most frequent co-medications. RESULTS: The overall
      prevalence of RLS was 27%. In the RLS-affected patients, regular use or overuse
      of non-opioid analgesics frequently combined with caffeine was the major risk
      factor which significantly correlated with psychiatric and medical comorbidity.
      In a subsample of 172 patients who had seldom taken analgesics the prevalence of
      RLS was 9%, which corresponds with its prevalence in the general population.
      CONCLUSION: Neither antidepressants nor neuroleptics but non-opioid analgesics
      appear to be a major risk factor of RLS. Their regular use should be considered
      in studies of RLS-patients on psychotropic or other drugs. In this sample of
      secondary-care patients, ICD-10 classified depression or anxiety per se did not
      appear to be a risk factor of RLS.

PMID- 12204846
TI  - Derivation of stem taper from the pipe theory in a carbon balance framework.
AB  - A dynamic tree growth model is described. The model derives the development of
      stem taper and vertical distribution of branch basal area from the pipe model,
      assuming that reuse of active pipes is regulated by foliage dynamics in a
      vertically explicit crown with a foliage distribution of constant shape. Based on
      empirical findings, the pipe model was modified slightly to allow the
      foliage/sapwood ratio to vary as a function of distance from the treetop. Growth
      was derived from carbon balance in a stand of different size trees that may shade
      each other. The model was applied to old and middle-aged trees growing in dense
      and sparse stands of Scots pine for which stand-level measurements are available
      as a chronosequence, but individual trees have been measured only once. Measured
      trees were compared with corresponding simulated trees for stem taper and
      vertical distribution of branch basal area. The results indicated that the pipe
      model assumptions, combined with a model of tree growth, are capable of producing
      realistic predictions of the vertical distribution of stem and branch diameter in
      trees of different sizes in the stand. A comparison of the results with a simple
      form of the uniform stress theory showed good agreement between the two models.
      However, a significant difference was found between the measured relative
      contribution of heartwood to total stem diameter and the predicted share of
      disused pipes in the stem. A possible explanation for this discrepancy is that
      the transition from sapwood to heartwood is gradual rather than abrupt as assumed
      in the model. A modification of the pipe model to incorporate a gradual
      transition is outlined.

PMID- 12204847
TI  - Radial patterns of sap flow in woody stems of dominant and understory species:
      scaling errors associated with positioning of sensors.
AB  - We studied sap flow in dominant coniferous (Pinus sylvestris L.) and broadleaf
      (Populus canescens L.) species and in understory species (Prunus serotina Ehrh.
      and Rhododendron ponticum L.) by the heat field deformation (HFD) method. We
      attempted to identify possible errors arising during flow integration and scaling
      from single-point measurements to whole trees. Large systematic errors of -90 to
      300% were found when it was assumed that sap flow was uniform over the sapwood
      depth. Therefore, we recommend that the radial sap flow pattern should be
      determined first using sensors with multiple measuring points along a stem radius
      followed by single-point measurements with sensors placed at a predetermined
      depth. Other significant errors occurred in the scaling procedure even when the
      sap flow radial pattern was known. These included errors associated with
      uncertainties in the positioning of sensors beneath the cambium (up to 15% per 1
      mm error in estimated xylem depth), and differences in environmental conditions
      when the radial profile applied for integration was determined over the short
      term (up to 47% error). High temporal variation in the point-to-area correction
      factor along the xylem radius used for flow integration is also problematic.
      Compared with midday measurements, measurements of radial variation of sap flow
      in the morning and evening of sunny days minimized the influence of temporal
      variations on the point-to-area correction factor, which was especially
      pronounced in trees with a highly asymmetric sap flow radial pattern because of
      differences in functioning of the sapwood xylem layers. Positioning a single
      point sensor at a depth with maximum sap flow is advantageous because of the high
      sensitivity of maximum sap flow to water stress conditions and changes in micro
      climate, and because of the lower random errors associated with the positioning
      of a single-point sensor along the xylem radius.

PMID- 12204848
TI  - Effects of summer drought and winter freezing on stem hydraulic conductivity of
      Rhododendron species from contrasting climates.
AB  - We studied the limits to maximum water transport in three diffuse-porous
      evergreen shrubs exposed to frequent winter freeze-thaw events (Rhododendron
      maximum L. and R. catawbiense Michaux from the Appalachian Mountains) and to a
      severe summer drought (R. macrophyllum G. Don. from the Oregon Cascades). Percent
      loss of hydraulic conductivity (PLC), vulnerability curves to xylem embolism and
      freezing point temperatures of stems were measured over 2 years. Controlled
      freeze-thaw experiments were also conducted to determine the effect of thaw rate
      on PLC. During both years, native PLC was significantly higher in winter than in
      summer for R. macrophyllum. Seasonal changes in PLC were variable in both R.
      catawbiense and R. maximum. Only R. maximum plants growing in gaps or clearings
      showed higher PLC than understory plants. A rapid (2-4 day) natural recovery of
      high native PLC during the winter was observed in both R. maximum and R.
      macrophyllum. Compared with the bench-dehydration method, vulnerability curves
      based on the air-injection method consistently had less negative slopes and
      greater variation. Fifty percent PLC (PLC(50)) obtained from vulnerability curves
      based on the dehydration method occurred at -1.75, -2.42 and -2.96 MPa for R.
      catawbiense, R. maximum and R. macrophyllum, respectively. Among the study
      species, R. macrophyllum, which commonly experiences a summer drought, had the
      most negative water potential at PLC(50). In all species, stem freezing point
      temperatures were not consistently lower in winter than in summer. A single fast
      freeze-thaw event significantly increased PLC, and R. catawbiense had the highest
      PLC in response to freezing treatments. Recovery to control PLC values occurred
      if a low positive hydraulic pressure was maintained during thawing. Rhododendron
      macrophyllum plants, which commonly experience few freeze-thaw events, had large
      stem diameters, whereas plants of R. catawbiense, which had small stem diameters,
      suffered high embolism in response to a single freeze-thaw event. Both drought
      induced and winter-induced embolism caused a significant reduction in hydraulic
      conductivity in all species during periods when drought or freeze-thaw events
      occurred in their native habitats. However, rapid recovery of PLC following
      freezing or drought maintained the species above their relatively low margins of
      safety for complete xylem dysfunction.

PMID- 12204849
TI  - Effects of crown development on leaf irradiance, leaf morphology and
      photosynthetic capacity in a peach tree.
AB  - The three-dimensional (3-D) architecture of a peach tree (Prunus persica L.
      Batsch) growing in an orchard near Avignon, France, was digitized in April 1999
      and again four weeks later in May 1999 to quantify increases in leaf area and
      crown volume as shoots developed. A 3-D model of radiation transfer was used to
      determine effects of changes in leaf area density and canopy volume on the
      spatial distribution of absorbed quantum irradiance (PAR(a)). Effects of changes
      in PAR(a) on leaf morphological and physiological properties were determined.
      Leaf mass per unit area (M(a)) and leaf nitrogen concentration per unit leaf area
      (N(a)) were both nonlinearly related to PAR(a), and there was a weak linear
      relationship between leaf nitrogen concentration per unit leaf mass (N(m)) and
      PAR(a). Photosynthetic capacity, defined as maximal rates of ribulose-1,5
      bisphosphate carboxylase (Rubisco) carboxylation (V(cmax)) and electron transport
      (J(max)), was measured on leaf samples representing sunlit and shaded micro
      environments at the same time that the tree crown was digitized. Both V(cmax) and
      J(max) were linearly related to N(a) during May, but not in April when the range
      of N(a) was low. Photosynthetic capacity per unit N(a) appeared to decline
      between April and May. Variability in leaf nitrogen partitioning between Rubisco
      carboxylation and electron transport was small, and the partitioning coefficients
      were unrelated to N(a). Spatial variability in photosynthetic capacity resulted
      from acclimation to varying PAR(a) as the crown developed, and acclimation was
      driven principally by changes in M(a) rather than the amount or partitioning of
      leaf nitrogen.

PMID- 12204850
TI  - Defense chemistry of cyanogenic Eucalyptus cladocalyx seedlings is affected by
      water supply.
AB  - Cyanogenesis is a widespread and effective defense mechanism in plants. Published
      evidence suggests that cyanogenic capacity (i.e., cyanogenic glycoside
      concentration) is enhanced in response to water stress, although potentially
      confounding variables preclude a definite conclusion. We used highly cyanogenic
      Eucalyptus cladocalyx var. nana F. Muell. seedlings grown with varying amounts of
      water and nitrogen (N) to determine the relationship between cyanogenic capacity
      and water stress. We also examined whether variation in cyanogenic capacity
      affects phenolic biosynthesis because both pathways use phenylalanine as a
      substrate. Cyanogenic capacity in fully expanded leaves increased 70% in response
      to moderate water stress when N availability was high but only 30% when growth
      was N-limited. Absolute cyanogenic capacity also increased with increasing N
      supply. Total phenolics and condensed tannins decreased with increasing N supply,
      but these compounds were unaffected by water stress. We conclude that, under the
      influence of water stress, the enhanced demand for phenylalanine for cyanogenic
      glycoside biosynthesis can be sustained by enhanced shikimate pathway flux
      without affecting phenolic metabolism.

PMID- 12204851
TI  - Shoot development, chlorophyll, gas exchange and carbohydrates in lychee
      seedlings (Litchi chinensis).
AB  - Shoot growth, chlorophyll concentrations, gas exchange and starch concentrations
      were studied in lychee (Litchi chinensis Sonn.) seedlings of cultivar "Wai Chee"
      grown in a heated greenhouse at Nambour in subtropical Australia (27 degrees S).
      We also examined the effects of shoot defoliation and root pruning on leaf
      expansion. Shoot growth showed a rhythmic cycle under constant greenhouse
      conditions, with a mean duration of flushing of 20 days and an interval of 10
      days over three cycles. Shoots and leaves expanded in a sigmoidal pattern to
      about 80 mm and 500 cm(2), respectively, for each flush. Starch concentrations of
      the lower stem and roots decreased as the young red leaves expanded, and
      increased as the fully expanded leaves turned dark green. Chlorophyll
      concentrations and net CO(2) assimilation rate were highest in the fully expanded
      dark green leaves. Removing 50% of the area of each fully expanded leaf had
      little effect on the expansion of younger leaves, but total biomass of defoliated
      plants was only 60% of that of controls. In contrast, removing half the roots
      just before bud swelling reduced final leaf area by 80%. We conclude that the
      young shoot has relatively low rates of photoassimilation until the leaves are
      fully expanded and dark green, and depends on assimilates from elsewhere in the
      plant. During leaf expansion, translocation of assimilates to the shoot occurred
      at the expense of the roots.

PMID- 12204852
TI  - Effects of leaf, shoot and fruit development on photosynthesis of lychee trees
      (Litchi chinensis).
AB  - Changes in gas exchange with leaf age and fruit growth were determined in lychee
      trees (Litchi chinensis Sonn.) growing in subtropical Queensland (27 degrees S).
      Leaves expanded in a sigmoid pattern over 50 days during spring, with net CO2
      assimilation (A) increasing from -4.1 +/- 0.9 to 8.3 +/- 0.5 micromol m-2 s-1 as
      the leaves changed from soft and red, to soft and light green, to hard and dark
      green. Over the same period, dark respiration (Rd) decreased from 5.0 +/- 0.8 to
      2.0 +/- 0.1 micromol CO2 m-2 s-1. Net CO2 assimilation was above zero about 30
      days after leaf emergence or when the leaves were half fully expanded.
      Chlorophyll concentrations increased from 0.7 +/- 0.2 mg g-1 in young red leaves
      to 10.3 +/- 0.7 mg g-1 in dark green leaves, along with stomatal conductance (gs,
      from 0.16 +/- 0.09 to 0.47 +/- 0.17 mol H2O m-2 s-1). Fruit growth was sigmoidal,
      with maximum values of fresh mass (29 g), dry mass (6 g) and fruit surface area
      (39 cm2) occurring 97 to 115 days after fruit set. Fruit CO2 exchange in the
      light (Rl) and dark (Rd) decreased from fruit set to fruit maturity, whether
      expressed on a surface area (10 to 3 micromol CO2 m-2 s-1 and 20 to 3 micromol
      CO2 m-2 s-1, respectively) or on a dry mass basis (24 to 2 nmol CO2 g-1 s-1 and
      33 to 2 nmol CO2 g-1 s-1, respectively). Photosynthesis never exceeded
      respiration, however, the difference between Rl and Rd was greatest in young
      green fruit (4 to 8 micromol CO2 m-2 s-1). About 90% of the carbon required for
      fruit growth was accounted for in the dry matter of the fruit, with the remainder
      required for respiration. Fruit photosynthesis contributed about 3% of the total
      carbon requirement of the fruit over the season. Fruit growth was mainly
      dependent on CO2 assimilation in recently expanded dark green leaves.

PMID- 12204853
TI  - Genomics and acute respiratory distress syndrome.

PMID- 12204854
TI  - Exercise carbon dioxide retention in chronic obstructive pulmonary disease: a
      case for ventilation/perfusion mismatch combined with hyperinflation.

PMID- 12204855
TI  - The adaptive response of smokers to oxidative stress: moving from culture to
      tissue.

PMID- 12204856
TI  - p21(CIP1/WAF1) and the immunologic fate of macrophages in smokers: at the
      crossroad between proliferation, survival, and death.

PMID- 12204857
TI  - Serendipity times two: fiberoptic bronchoscopy becomes a medical procedure.

PMID- 12204858
TI  - Diffuse alveolar hemorrhage in hematopoietic stem cell transplant recipients.

PMID- 12204859
TI  - Angiotensin converting enzyme insertion/deletion polymorphism is associated with
      susceptibility and outcome in acute respiratory distress syndrome.
AB  - Acute respiratory distress syndrome (ARDS) is an often fatal condition for which
      a genetic predisposition is postulated, although no specific genes have been
      identified to date. Angiotensin converting enzyme (ACE) has a potential role in
      the pathogenesis of ARDS via effects on pulmonary vascular tone/permeability,
      epithelial cell survival, and fibroblast activation. Forty-seven percent of the
      variance in plasma ACE activity is accounted for by the ACE insertion/deletion
      (I/D) polymorphism, the D allele being associated with higher activity. We
      therefore hypothesized that the presence of the D allele would be associated with
      the development of ARDS. Ninety-six white patients fulfilling American/European
      Consensus Committee criteria for ARDS were genotyped for the ACE polymorphism
      together with individuals from three comparison groups: 88 white patients with
      non-ARDS respiratory failure ventilated in the intensive care unit (ICU), 174 ICU
      patients undergoing coronary artery bypass grafting, and 1,906 individuals from a
      general population group. DD genotype frequency was increased in the patients
      with ARDS compared with the ICU (p = 0.00008), coronary artery bypass grafting (p
      = 0.0009), and general population group (p = 0.00004) control groups and was
      significantly associated with mortality in the ARDS group (p < 0.02). These data
      suggest a potential role for renin-angiotensin systems in the pathogenesis of
      ARDS and for the first time implicate genetic factors in the development and
      progression of this syndrome.

PMID- 12204860
TI  - Tumor necrosis factor-alpha and angiostatin are mediators of endothelial
      cytotoxicity in bronchoalveolar lavages of patients with acute respiratory
      distress syndrome.
AB  - Acute respiratory distress syndrome (ARDS) is characterized by an extensive
      alveolar capillary leak, permitting contact between intra-alveolar factors and
      the endothelium. To investigate whether factors contained in the alveolar milieu
      induce cell death in human lung microvascular endothelial cells, we exposed these
      cells in vitro to bronchoalveolar lavage fluid (BALF) supernatants from control
      patients, patients at risk of developing ARDS, and patients with early- and late
      phase ARDS. In contrast to BALF from control patients, a significant cytotoxicity
      was found in BALF from patients at risk of developing ARDS, with late-phase ARDS,
      and especially from patients with early-phase ARDS. Subsequently, we determined
      the levels of factors known to exert cytotoxicity in endothelial cells, i.e.,
      tumor necrosis factor (TNF)-alpha, transforming growth factor (TGF)-beta1, and
      angiostatin. BALF from patients at risk of developing ARDS, with early-phase
      ARDS, and with late-phase ARDS, contained increased levels of TNF-alpha and
      angiostatin, but not of TGF-beta1, as compared with BALF from control patients.
      Whereas inhibition of TGF-beta1 had no effect in this setting, neutralization of
      TNF-alpha or angiostatin inhibited the cytotoxic activity on endothelial cells of
      part of the early-phase ARDS BALF. These results indicate that TNF-alpha and
      angiostatin may contribute to ARDS-related endothelial injury.

PMID- 12204861
TI  - Platelet-activating factor-induced pulmonary edema is partly mediated by
      prostaglandin E(2), E-prostanoid 3-receptors, and potassium channels.
AB  - Platelet-activating factor (PAF) is an important endogenous mediator of pulmonary
      edema in many models of acute lung injury. PAF triggers edema formation by
      simultaneous activation of two independent pathways; one is mediated by a
      cyclooxygenase metabolite, and the other is blocked by quinine. We examined the
      hypothesis that the cyclooxygenase-dependent part of PAF-induced edema is
      mediated by prostaglandin E(2) (PGE(2)). In isolated rat lungs, PAF
      administration stimulated release of PGE(2) into the venous effluate and
      increased lung weight as a measure of edema formation. Perfusion with a
      neutralizing PGE(2) antibody attenuated the PAF-induced edema formation. In vivo,
      E-prostanoid 3-receptor-deficient mice showed less pulmonary Evans blue
      extravasation in response to PAF injection than did mice deficient in EP1, EP2,
      or EP4 receptors. Perfusion of rat lungs with PGE(2) caused pulmonary edema,
      which was largely prevented by inhibition of voltage-gated potassium channels (25
      nM beta-dendrotoxin), but not by blocking calcium-dependent potassium currents
      (100 micro M paxilline). In line with its effects on PGE(2)-induced edema
      formation, beta-dendrotoxin attenuated PAF-induced edema partly if given alone,
      and completely in combination with quinine. Our findings suggest that PAF
      triggered edema is partly mediated by the release of PGE(2), activation of EP3
      receptors, and activation of voltage-gated potassium channels.

PMID- 12204862
TI  - Exercise hypercapnia in advanced chronic obstructive pulmonary disease: the role
      of lung hyperinflation.
AB  - In severe chronic obstructive pulmonary disease (COPD), carbon dioxide retention
      during exercise is highly variable and is poorly predicted by resting pulmonary
      function and arterial blood gases or by tests of ventilatory control. We reasoned
      that in patients with compromised gas exchange capabilities, exercise hypercapnia
      could be explained, in part, by the restrictive consequences of dynamic lung
      hyperinflation. We studied 20 stable patients with COPD (FEV(1) = 34 +/- 3
      percent predicted; mean +/- SEM) with varying gas exchange abnormalities
      (Pa(O(2)) range, 35 to 84 mm Hg; Pa(CO(2)) range, 31 to 64 mm Hg). During symptom
      limited maximum cycle exercise breathing room air, Pa(CO(2)) increased 7 +/- 1 mm
      Hg (p < 0.05) from rest to peak exercise (range, -6 to 25 mm Hg). We measured the
      change in Pa(CO(2)) after hyperoxic breathing at rest as an indirect test of
      ventilation-perfusion abnormalities. The change in Pa(CO(2)) from rest to peak
      exercise correlated best with the acute change in Pa(CO(2)) during hyperoxia at
      rest (r(2) = 0.62, p < 0.0005) and with resting arterial oxygen saturation (r(2)
      = 0.30, p = 0.011). During exercise, the strongest correlates of serial changes
      in Pa(CO(2)) from rest included concurrent changes in end-expiratory lung volume
      expressed as a percentage of total lung capacity (partial correlation coefficient
      [r] = 0.562, p < 0.0005) and oxygen saturation (partial r = 0.816, p < 0.0005).
      In severe COPD, the propensity to develop carbon dioxide retention during
      exercise reflects marked ventilatory constraints as a result of lung
      hyperinflation as well as reduced gas exchange capabilities.

PMID- 12204863
TI  - Comparison of effects of strength and endurance training in patients with chronic
      obstructive pulmonary disease.
AB  - We determined the effect of different exercise training modalities in patients
      with chronic obstructive pulmonary disease, including strength training (n = 17),
      endurance training (n = 16), and combined strength and endurance (n = 14) (half
      of the endurance and half of the strengthening exercises). Data were compared at
      baseline, the end of the 12-week exercise-training program, and 12 weeks later.
      Improvement in the walking distance was only significant in the strength group.
      Increases in submaximal exercise capacity for the endurance group were
      significantly higher than those observed in the strength group but were of
      similar magnitude than those in the combined training modality, which in turn
      were significantly higher than for the strength group. Increases in the strength
      of the muscle groups measured in five weight lifting exercises were significantly
      higher in the strength group than in the endurance group but were of similar
      magnitude than in the combined training group, which again showed significantly
      higher increases than subjects in the endurance group. Any training modality
      showed significant improvements of the breathlessness score and the dyspnea
      dimension of the chronic respiratory questionnaire. In conclusion, the
      combination of strength and endurance training seems an adequate training
      strategy for chronic obstructive pulmonary disease patients.

PMID- 12204864
TI  - Smoking and lung function of Lung Health Study participants after 11 years.
AB  - Eleven years after Lung Health Study (LHS) entry, we performed spirometry in
      77.4% of surviving participants who enrolled in a long-term follow-up study.
      Those not enrolling tended to be younger male heavy smokers who continued to
      smoke during the LHS. Their initial LHS lung function, after adjustment for these
      factors, did not differ from that of enrollees. Smoking habits by original LHS
      treatment groups (smoking intervention vs. usual care) tended to converge, but
      93% of participants who were abstinent throughout the LHS were still abstinent at
      11 years. Differences in lung function between treatment groups persisted;
      smoking intervention participants had less decline in FEV(1) than usual care
      participants. Men who quit at the beginning of the LHS had an FEV(1) rate of
      decline of 30.2 ml/year, whereas women who quit declined at 21.5 ml/year. Men
      continuing to smoke throughout the 11 years declined by 66.1 ml/year, and women
      continuing to smoke declined by 54.2 ml/year. When decline in FEV(1) was
      expressed as a percentage of predicted normal value, no significant sex-based
      difference was apparent among continuing smokers. At 11 years, 38% of continuing
      smokers had an FEV(1) less than 60% of the predicted normal value compared with
      10% of sustained quitters.

PMID- 12204865
TI  - Health-related quality of life and mortality in male patients with chronic
      obstructive pulmonary disease.
AB  - To assess whether generic and specific health-related quality of life (HRQL) are
      independently associated with total and specific mortality in patients with
      chronic obstructive pulmonary disease (COPD), we followed until 1999 a cohort of
      321 male patients with COPD, recruited in 1993-1994 at outpatient respiratory
      clinics. Baseline characteristics recorded under stable clinical conditions
      included forced spirometry, arterial blood gas tensions, dyspnea scales, 11
      comorbid conditions, St. George's Respiratory Questionnaire (SGRQ), and SF-36
      Health Survey. Vital status was assessed through reinterviews, the Mortality
      Register, and clinical records. Subjects who died (106) were older (69.8 versus
      62.5 years) (p < 0.001), had lower body mass index (BMI) (25.4 versus 27.1) (p <
      0.01), were more impaired in the clinical characteristics studied (%FEV(1), 34.0
      versus 51.0) (p < 0.001), and had long-term oxygen therapy more frequently (31%
      versus 7%) (p < 0.001). Survival was shorter when worse HRQL was reported. SGRQ
      total and SF-36 physical summary scores were independently associated with total
      and respiratory mortality in Cox models, including age, FEV(1), and BMI. The
      total mortality-standardized hazard ratios for both HRQL measures were 1.3,
      whereas those for FEV(1) were 1.6. HRQL measures provide independent and relevant
      information on the health status of male patients with COPD. Their use should be
      considered for a more thorough evaluation and staging of patients with COPD.

PMID- 12204866
TI  - A functional polymorphism in the RANTES gene promoter is associated with the
      development of late-onset asthma.
AB  - The CC chemokine regulated upon activation, normal T-cell expressed and secreted
      (RANTES) attracts eosinophils, basophils, and T cells during inflammation and
      immune response, indicating a possible role for this chemokine in asthma. Both
      the -403A and -28G alleles of the RANTES promoter region exhibit significantly
      enhanced promoter activity in reporter constructs in vitro. We therefore
      investigated the genetic influence of these alleles on the development of asthma
      using case-control analysis in a Japanese population (298 patients with asthma
      and 311 control subjects). Given the evidence for heterogeneity of asthma
      according to age at onset, we divided patients with asthma into three subgroups:
      117 late-onset patients with asthma (onset at more than 40 years of age), 83
      middle-onset patients with asthma (onset at 20 to 40 years of age), and 98 early
      onset patients with asthma (onset at less than 20 years of age). The -28G allele
      was significantly associated with late-onset asthma (odds ratio = 2.033; 95%
      confidence interval, 1.379-2.998; corrected p < 0.0025) but was not associated
      with the other two asthma subgroups. The -403A allele was not associated with any
      of the asthma subgroups. Further evidence of the importance of the -28G allele
      was a significant increase in the production of RANTES in vitro in individuals
      who carried this allele. Our findings suggest that, among Japanese, the -28G
      allele of the RANTES promoter region confers susceptibility to late-onset asthma.

PMID- 12204867
TI  - The impact of oral corticosteroid use on bone mineral density and vertebral
      fracture.
AB  - The use of oral corticosteroids is associated with an increased risk of fracture,
      but there is limited information on the relationship between corticosteroid dose,
      bone mineral density (BMD), and fracture. We examined this relationship in a
      community population (more than 50 years) taking oral corticosteroids for chronic
      lung disease. Details of corticosteroid use and lifestyle were obtained by
      questionnaire, general practice records, and patient interview. BMD was assessed
      at the lumbar spine and femur and vertebral fracture by morphometric X-ray
      absorptiometry. Of the 117 patients who participated (median age, 69), 48% were
      female. Fifty-eight percent had osteoporosis (a T score of less than -2.5), and
      61% had a vertebral fracture. The presence of vertebral fracture was related to
      BMD at the femoral neck, with an odds ratio of 1.6 for a 1 SD reduction in BMD.
      The cumulative prednisolone dose ranged from 3.4 to 175 g and was strongly
      associated with vertebral fracture, with the odds ratio between the highest and
      lowest dose quartiles being 4.4 (95% confidence interval, 1.04, 18.8). The
      difference in femoral neck BMD between the same dose quartiles was only modest,
      however (0.5 SD; 95% confidence interval, 0.09, 0.94). In patients taking long
      term oral corticosteroids for chronic lung disease, the relationship between
      vertebral fracture risk and BMD is similar to that seen in other populations.
      Cumulative prednisolone dose is strongly related to fracture risk, and this
      effect is independent of its more modest impact on BMD.

PMID- 12204868
TI  - Effect of cat and dog ownership on sensitization and development of asthma among
      preteenage children.
AB  - An inverse relationship has been proposed between exposure to high quantities of
      cat allergen at home and both asthma and cat allergy. First- and second-grade
      children from Lulea, Kiruna, and Pitea, Sweden participated in an asthma
      questionnaire study (n = 3,431) and incidence was evaluated over the next 3
      years. Skin testing was performed on the children in Lulea and Kiruna (n =
      2,149). The strongest risk factor for incident cases of asthma was Type 1 allergy
      (relative risk [RR], 4.9 [2.9-8.4]), followed by a family history of asthma (RR,
      2.83 [1.8-4.5]). Living with a cat was inversely related both to having a
      positive skin test to cat (RR, 0.62 [0.47-0.83]) and incidence of physician
      diagnosed asthma (RR, 0.49 [0.28-0.83]). This effect on incident asthma was most
      pronounced among the children with a family history of asthma (RR, 0.25 [0.08
      0.80]). The evidence also suggests that many of the children exposed to cats at
      home can develop an immune response that does not include immunoglobulin E.
      Weaker protective trends were seen with dog ownership. The traditional thinking
      that not owning cats can provide protection against developing allergy and asthma
      among those with a family history of allergy needs to be re-evaluated. In a
      community where cat sensitization was strongly associated with asthma, owning a
      cat was protective against both prevalent and incident asthma.

PMID- 12204869
TI  - Antioxidant supplementation and lung functions among children with asthma exposed
      to high levels of air pollutants.
AB  - To evaluate whether acute effects of ozone, nitrogen dioxide, and particulates
      with mass median diameter less than 10 micro m could be attenuated by antioxidant
      vitamin supplementation, we conducted a randomized trial using a double-blinded
      design. Children with asthma (n = 158) who were residents of Mexico City were
      randomly given a daily supplement of vitamins (50 mg/day of vitamin E and 250
      mg/day of vitamin C) or a placebo and were followed from October 1998 to April
      2000. Pulmonary function tests were carried out twice a week in the morning.
      During the follow-up observation period, the mean 1-hour maximum ozone level was
      102 ppb (SD = 47), and the mean 24-hour average PM(10) level was 56.7 micro
      g/m(3) (SD = 27.4). In children with moderate and severe asthma, ozone levels 1
      day before spirometry were inversely associated significantly with forced
      expiratory flow (FEF(25-75)) (-13.32 ml/second/10 ppb; p = 0.000), FEV(1) (-4.59
      ml/10 ppb; p = 0.036), and peak expiratory flow (PEF) (-15.01 ml/second/10 ppb; p
      = 0.04) in the placebo group after adjusting for potential confounding factors.
      No association between ozone and lung functions was observed in the supplement
      group. We observed significant differences in lung function decrements between
      groups for FEF(25-75) and PEF. Our results suggest that supplementation with
      antioxidants might modulate the impact of ozone exposure on the small airways of
      children with moderate to severe asthma.

PMID- 12204872
TI  - Increased p21(CIP1/WAF1) and B cell lymphoma leukemia-x(L) expression and reduced
      apoptosis in alveolar macrophages from smokers.
AB  - Alveolar macrophages (AMs) are the predominant defense cells in the airway, and
      their numbers are increased in smokers and subjects with chronic obstructive
      pulmonary disease. This increase may result from increased recruitment, increased
      proliferation, or reduced cell death. Apoptosis regulates inflammatory cell
      survival, and p21(CIP1/WAF1) is an important inhibitory regulator of cycle
      progression after oxidative stress. We have investigated whether chronic smoke
      exposure influences the expression and localization of cell cycle and apoptotic
      proteins in AM and bronchial epithelial cells in vivo. The increased numbers of
      AMs seen in smokers were only partially due to enhanced proliferation.
      p21(CIP1/WAF1) protein expression was increased in AMs and biopsies isolated from
      smokers and was found predominantly within the cytoplasm. In addition, B cell
      lymphoma leukemia (Bcl)-x(L), an antiapoptotic regulator, was also highly
      expressed in macrophages from smokers compared with nonsmokers and subjects with
      asthma. Hydrogen peroxide, an oxidative stress, induced cytoplasmic expression of
      p21(CIP1/WAF1) and failed to induce apoptosis in an in vitro model. These results
      suggested that AM and bronchial epithelial cells from smokers, in contrast to
      those from normal subjects and subjects with asthma, have reduced cell death.
      Thus, oxidative stress induced by cigarette smoking may contribute to the
      chronicity of inflammation in the airway, through a reduction of apoptosis.

PMID- 12204870
TI  - Effects of glutathione-S-transferase M1, T1, and P1 on childhood lung function
      growth.
AB  - The effects of glutathione-S-transferase (GST) M1, GSTT1, and GSTP1 genotypes on
      lung function growth were investigated in 1,940 children enrolled in the
      Children's Health Study as fourth graders (aged 8-11 years) in two cohorts during
      1993 and 1996 and were followed annually over a 4-year period. Genotypes for
      GSTM1 and GSTT1 and GSTP1 codon 105 variants (ile105 and val105) were determined
      using DNA from buccal cell specimens. We used two-level regression models to
      estimate the effects of GSTM1, GSTT1, and GSTP1 genotypes on the adjusted annual
      average lung function growth. GSTM1 null was associated with deficits in annual
      growth rates for FVC (-0.21%; 95% confidence interval [CI], -0.40, -0.03) and
      FEV(1) (-0.27%; 95% CI, -0.50, -0.04). Children who were homozygous for the GSTP1
      val105 allele had slower lung function growth (FVC -0.35%; 95% CI, -0.62, -0.07;
      and FEV(1) -0.34%; 95% CI, -0.68, 0.00) than children with one or more ile105
      alleles. Children with asthma who were homozygous for the GSTP1 val105 allele had
      substantially larger deficits in FVC, FEV(1), and maximal mid-expiratory flow
      than children without asthma. The deficits in FVC and FEV(1) growth associated
      with both GSTM1 null and the GSTP1 val105 allele were largest and were
      statistically significant in non-Hispanic white children. We conclude that GSTM1
      and GSTP1 genotypes are associated with lung function growth in school children.

PMID- 12204871
TI  - Severe community-acquired pneumonia: use of intensive care services and
      evaluation of American and British Thoracic Society Diagnostic criteria.
AB  - Despite careful evaluation of changes in hospital care for community-acquired
      pneumonia (CAP), little is known about intensive care unit (ICU) use in the
      treatment of this disease. There are criteria that define CAP as "severe," but
      evaluation of their predictive value is limited. We compared characteristics,
      course, and outcome of inpatients who did (n = 170) and did not (n = 1,169)
      receive ICU care in the Pneumonia Patient Outcomes Research Team prospective
      cohort. We also assessed the predictive characteristics of four prediction rules
      (the original and revised American Thoracic Society criteria, the British
      Thoracic Society criteria, and the Pneumonia Severity Index [PSI]) for ICU
      admission, mechanical ventilation, medical complications, and death (as proxies
      for severe CAP). ICU patients were more likely to be admitted from home and had
      more comorbid conditions. Reasons for ICU admission included respiratory failure
      (57%), hemodynamic monitoring (32%), and shock (16%). ICU patients incurred
      longer hospital stays (23.2 vs. 9.1 days, p < 0.001), higher hospital costs
      (21,144 dollars vs. 5,785 dollars, p < 0.001), more nonpulmonary organ
      dysfunction, and higher hospital mortality (18.2 vs. 5.0%, p < 0.001). Although
      ICU patients were sicker, 27% were of low risk (PSI Risk Classes I-III). Severity
      adjusted ICU admission rates varied across institutions, but mechanical
      ventilation rates did not. The revised American Thoracic Society criteria rule
      was the best discriminator of ICU admission and mechanical ventilation (area
      under the receiver operating characteristic curve, 0.68 and 0.74, respectively)
      but none of the prediction rules were particularly good. The PSI was the best
      predictor of medical complications and death (area under the receiver operating
      characteristic curve, 0.65 and 0.75, respectively), but again, none of the
      prediction rules were particularly good. In conclusion, ICU use for CAP is common
      and expensive but admission rates are variable. Clinical prediction rules for
      severe CAP do not appear adequately robust to guide clinical care at the current
      time.

PMID- 12204873
TI  - Gene therapy with galectin-3 inhibits bronchial obstruction and inflammation in
      antigen-challenged rats through interleukin-5 gene downregulation.
AB  - The pathophysiology of asthma involves an intricate network of molecular and
      cellular interactions. Elevated Th2 cytokines (interleukin [IL]-5 and IL-4)
      associated with eosinophilic inflammation characterize allergic diseases and
      provide potential targets for immunomodulation. Recent evidence has demonstrated
      that galectin-3 induces selective downregulation of IL-5 gene expression in
      several cell types (eosinophils, T cell lines, and antigen specific T cells).
      Accordingly, we sought to elucidate whether in vivo intratracheal instillation of
      plasmid DNA encoding galectin-3 would inhibit an experimental asthmatic reaction
      in a rat model with increased eosinophils and T cells in bronchoalveolar fluid
      and impaired pulmonary function. We found that instillation of galectin-3 gene in
      these rats led to normalization of the eosinophil and T cell count in
      bronchoalveolar lavage fluid and that there was a strong concomitant inhibition
      of IL-5 mRNA in the lungs. As a consequence, galectin-3-treated rats showed
      recovery of pulmonary functional parameters, such as pulmonary pressure and
      expiratory flows. These data emphasize the potential utility of galectin-3 as a
      novel therapeutic approach for treatment of allergic asthma.

PMID- 12204874
TI  - Cysteinyl leukotrienes promote human airway smooth muscle migration.
AB  - Cysteinyl leukotrienes promote airway smooth muscle (ASM) contraction and
      proliferation. Little is known about their role in ASM migration. We investigated
      this using cultured human ASMs (between the second and fifth passages) obtained
      from the large airways of resected nonasthmatic lung. Platelet-derived growth
      factor-BB (1 ng/ml) promoted significant (3.5-fold) ASM migration of myocytes
      across collagen-coated 8- micro m polycarbonate membranes in Transwell culture
      plates. Leukotriene E(4) (10(-7), 10(-8), 10(-9) M) did not demonstrate a
      chemotactic effect; it did promote chemokinesis. Priming by leukotriene E(4) (10(
      7) M) significantly augmented the directional migratory response to platelet
      derived growth factor (1.5-fold, p < 0.05). This was blocked by montelukast (10(
      6) M), demonstrating the effect to be mediated by the cysteinyl leukotriene
      receptor. The "priming effect" was also partially attenuated by prostaglandin
      E(2) (10(-7) M). Whereas both the chemokinetic and the chemotactic "primed"
      responses were equally attenuated by a p38 mitogen-activated protein kinase
      inhibitor (SB203580, 25 micro M) and by a Rho-kinase inhibitor (Y27632, 10 micro
      M), the chemotactic response showed greater inhibition than chemokinesis by a
      phosphatidylinositol-3 kinase inhibitor (LY294002, 50 micro M). These experiments
      suggest that cysteinyl leukotrienes play an augmentary role in human ASM
      migration. The phosphatidylinositol-3 kinase pathway is a key signaling mechanism
      in the chemotactic migration of ASM cells in response to cysteinyl leukotrienes.

PMID- 12204875
TI  - Oral appliance therapy improves symptoms in obstructive sleep apnea: a
      randomized, controlled trial.
AB  - The aim of this study was to evaluate the effect of a mandibular advancement
      splint (MAS) on daytime sleepiness and a range of other symptoms in obstructive
      sleep apnea (OSA). Using a randomized crossover design, patients received 4 weeks
      of treatment with MAS and a control device (inactive oral appliance), with an
      intervening 1-week washout. At the end of each treatment period, patients were
      reassessed by questionnaire, polysomnography, and multiple sleep latency test.
      Fifty-nine men and 14 women with a mean (+/- SD) age of 48 +/- 11 years and
      proven OSA experienced a significantly improved mean (+/- SEM) sleep latency on
      the multiple sleep latency test (10.3 +/- 0.5 versus 9.1 +/- 0.5 minutes, p =
      0.01) and Epworth sleepiness scale score (7 +/- 1 versus 9 +/- 1, p < 0.0001)
      with the MAS compared with the control device after 4 weeks. The proportion of
      patients with normal subjective sleepiness was significantly higher with the MAS
      than with the control device (82 versus 62%, p < 0.01), but this was not so for
      objective sleepiness (48 versus 34%, p = 0.08). Other OSA symptoms were
      controlled in significantly more patients with the MAS than with the control
      device. MAS therapy improves a range of symptoms associated with OSA.

PMID- 12204876
TI  - Peripheral blood mononuclear cell proliferation to heat shock protein-70 derived
      from autologous lung carcinoma.
AB  - In animals, tumor-derived heat shock proteins (HSP) induce immune-mediated
      protection against autologous cancer. We investigated whether HSP-70 derived from
      human lung carcinoma are also complexed to tumor-specific antigens. Peripheral
      blood mononuclear cells collected 10 days after surgery from patients with lung
      cancer were stimulated with HSP-70 purified from autologous and heterologous
      tumors. The stimulation index (SI) obtained when stimulating cells with
      autologous tumor-derived HSP-70 averaged 3.07 +/- 0.75 in patients with lung
      cancer and 1.57 +/- 0.33 in control subjects (p < 0.001 by analysis of variance).
      No significant stimulation was observed with HSP-70 derived either from the
      majority of heterologous tumors or from autologous tumor-free lung tissue. SI
      decreased from 3.59 +/- 0.65 to 1.65 +/- 0.38 in six patients tested again 3
      months after surgery (p = 0.02 by Wilcoxon test for paired data). HSP-70 derived
      from lung carcinoma are shown to be associated with T cell antigens. The T cell
      reactivity appears transient and restricted to antigens complexed to HSP-70
      derived from autologous tumors only. This suggests that the antigenicity of human
      lung tumors is unique, which may be crucial for the design of new vaccines.

PMID- 12204877
TI  - Diminished immunoreactivity of gamma-glutamylcysteine synthetase in the airways
      of smokers' lung.
AB  - Glutathione (GSH) plays a major role in protecting the airways against oxidative
      stress. The rate-limiting enzyme in de novo GSH synthesis is gamma
      glutamylcysteine synthetase (gamma-GCS), which is induced by acute exposure to
      GSH-depleting cytokines and oxidants, but downregulated by transforming growth
      factor beta and prolonged oxidant exposure, at least in vitro. Cell-specific
      expression or regulation of gamma-GCS may play an important role both in the
      defense against oxidants and in the pathogenesis of oxidant-associated airway
      diseases. In this study, the localizations of gamma-GCS heavy (gamma-GCS-HS) and
      light (gamma-GCS-LS) subunits were investigated by immunohistochemistry in 22
      patients with chronic obstructive pulmonary disease (COPD), 20 smokers without
      COPD, and 13 lifelong nonsmokers. The ultrastructural distributions of both gamma
      GCS subunits were assessed by immuno-electron microscopy. Both subunits were
      expressed most prominently in the large airways, and their ultrastructural
      localization was both cytoplasmic and along the plasma membrane. The expression
      of gamma-GCS-HS was stronger in the central bronchial epithelium than in the
      peripheral bronchioli (p = 0.020), or in alveolar macrophages (p = 0.008). The
      expression of gamma-GCS-HS in the central bronchial epithelium showed a tendency
      to be higher in nonsmokers compared with all smokers (p = 0.052). Alveolar
      macrophages of nonsmokers had higher levels of gamma-GCS-HS (p = 0.001) and gamma
      GCS-LS (p = 0.001) than did smokers. The expression of gamma-GCS-HS in the
      central bronchial epithelium was more marked in nonsmokers than in patients with
      COPD (p = 0.015), the difference between smokers and patients with COPD was not
      significant. In conclusion, the heavy and light subunits of gamma-GCS are mainly
      expressed in the large airways. Their tendency to decrease in cigarette smokers
      may further predispose lung cells to ongoing oxidant stress, which contributes to
      the progression of lung injury.

PMID- 12204878
TI  - Prone position increases collapsibility of the passive pharynx in infants and
      small children.
AB  - On the basis of two observations that avoiding prone sleeping decreased incidence
      of sudden infant death syndrome and that obstructive sleep apnea is closely
      linked with the syndrome, we hypothesized that the prone position may increase
      upper airway collapsibility in infants and small children. Passive pharyngeal
      collapsibility of 19 infants and small children (10-101 weeks old) was examined
      in three postures: supine with face straight up, supine with neck rotated, and
      prone with neck rotated. The collapsibility was evaluated with the maximal
      distension of the most collapsible region, pharyngeal stiffness, and pharyngeal
      closing pressure, estimated from static pressure-area relationship of the passive
      pharynx. No significant changes in pharyngeal stiffness were detected; however,
      maximal distension was reduced in the prone position (mean +/- SD, 0.56 +/- 0.26
      versus 0.44 +/- 0.20 cm(2); supine with face straight up versus prone position, p
      < 0.05). Pharyngeal closing pressure increased at neck rotation in the supine
      position (-4.5 +/- 2.4 versus -2.8 +/- 2.3 cm H(2)O; supine with face straight up
      versus supine with neck rotated, p < 0.05), and a further increase was observed
      in the prone position (-0.3 +/- 2.9 cm H(2)O, p < 0.05 versus supine with neck
      rotation). Pharyngeal closing pressure in the prone position was above
      atmospheric pressure in half of our subjects, whereas all subjects had negative
      pharyngeal pressure in the supine position. We conclude that the prone position
      increases upper airway collapsibility, although the mechanism is yet unclear.

PMID- 12204879
TI  - Basic fibroblast growth factor and its receptors in idiopathic pulmonary fibrosis
      and lymphangioleiomyomatosis.
AB  - Basic fibroblast growth factor (bFGF) is a potent mitogenic factor for smooth
      muscle cells, myofibroblasts, and fibroblasts, proliferation of which is a
      hallmark of idiopathic pulmonary fibrosis (IPF) and lymphangioleiomyomatosis
      (LAM). Mast cells produce bFGF and have been associated with pulmonary fibrosis.
      We hypothesize that smooth muscle cell/myofibroblast-like cells will be spatially
      associated with bFGF-containing mast cells and that bFGF receptors will be
      expressed on the effector cells in IPF and LAM. We performed quantitative
      immunohistochemistry for bFGF, mast cell tryptase, smooth muscle actin for smooth
      muscle cell/myofibroblast-like cells, and fibroblast growth factor receptors
      (Flg, Bek) and measured collagen and elastic fiber in lung sections from IPF (n =
      14), LAM (n = 9), and control lung (n = 10). IPF and LAM lung contained more
      smooth muscle cell/myofibroblast-like cells than did control lung. bFGF
      containing mast cells were abundant both in IPF and LAM and were associated with
      collagen, elastic fibers, and smooth muscle cell/myofibroblast-like cells in IPF.
      Flg was expressed on epithelial cells, endothelial cells, smooth muscle
      cell/myofibroblast-like cells, and macrophages in IPF. In LAM, Flg was expressed
      on epithelial cells adjacent to smooth muscle cell/myofibroblast-like cell
      aggregates. Bek was expressed dominantly on smooth muscle cell/myofibroblast-like
      cells in LAM and on smooth muscle cell/myofibroblast-like cells as well as
      neutrophils in IPF. These data suggest that mast cell-derived bFGF might exert
      fibrogenic, proliferative effects on smooth muscle cell/myofibroblast-like cells
      through its receptors.

PMID- 12204880
TI  - Familial aggregation of pulmonary function in a rural Chinese community.

PMID- 12204881
TI  - Application of an algorithm for the diagnosis of asthma in Chinese families:
      limitations and alternatives for the phenotypic assessment of asthma in family
      based genetic studies.

PMID- 12204882
TI  - Familial aggregation of bronchodilator response: a community-based study.

PMID- 12204883
TI  - Asthma, rhinitis, and skin test reactivity to aeroallergens in families of
      asthmatic subjects in Anqing, China.

PMID- 12204884
TI  - A comparison of myocardial function after primary cardiac and primary asphyxial
      cardiac arrest.

PMID- 12204885
TI  - Exposure-response relationship between paternal smoking and children's pulmonary
      function.

PMID- 12204886
TI  - Body mass index and asthma in adults in families of subjects with asthma in
      Anqing, China.

PMID- 12204887
TI  - Association of asthma with beta(2)-adrenergic receptor gene polymorphism and
      cigarette smoking.

PMID- 12204888
TI  - Modeling allergic asthma in mice: pitfalls and opportunities.
AB  - Studies in murine experimental models have contributed greatly to understanding
      the mechanisms of allergic inflammation underlying asthma. However, models
      involving short-term high-level exposure of sensitized animals to antigen have
      significant limitations for investigating the pathogenesis of the lesions of
      chronic asthma. Modeling chronic asthma is problematic, because long-term
      antigenic challenge often triggers widespread pulmonary parenchymal inflammation
      or leads to eventual downregulation of inflammation and airway hyperreactivity.
      We have developed an improved murine model in which animals are exposed to low
      mass concentrations of aerosolized antigen for 6-8 wk. The mice exhibit airway
      specific acute-on-chronic inflammation and changes of airway wall remodeling as
      seen in human asthma, together with hyperreactivity to a cholinergic agonist
      which can be specifically attributed to airway disease. This more realistic model
      of asthma offers a number of opportunities for investigation of pathogenetic
      mechanisms and novel therapeutic agents.

PMID- 12204889
TI  - Regulation of human Clara cell 10 kD protein expression by chicken ovalbumin
      upstream promoter transcription factors (COUP-TFs).
AB  - Clara cell 10 kD protein (CC10) is expressed specifically in a portion of
      nonciliated airway epithelial cells. The molecular mechanisms that determine its
      high specificity are not clear. Transcription factors implicated in the
      regulation of CC10 in rodents do not show the same level of cell specificity. We
      report here that a 3.3 kb human CC10 DNA fragment, containing the 5' flanking
      region and promoter, directs lacZ reporter expression in a small portion of Clara
      cells of the airway epithelia of transgenic mice, indicating the requirement of
      additional regulatory elements for expression. Addition of an intron containing a
      transcription enhancer from the human cytokeratin 18 gene greatly enhances the
      level of transgene expression and broadens epithelial specificity. To gain
      insight into the mechanisms underlying the cell specificity of human CC10
      expression, we performed a promoter analysis of the CC10 gene and a yeast one
      hybrid screening to identify factors that regulate the promoter. We have found
      that chicken ovalbumin upstream promoter transcription factors (COUP-TFs)
      interact with a proximal promoter region and confirmed the interaction by gel
      shift assays. Cotransfection analyses with reporter constructs in cultured cells
      indicated that COUP-TFs inhibit human CC10 expression. These experiments suggest
      that COUP-TFs may play a pivotal role in cell specificity of the human CC10 gene
      by inhibiting its expression in nonpermissive cells.

PMID- 12204890
TI  - Altered zinc homeostasis and caspase-3 activity in murine allergic airway
      inflammation.
AB  - Zn may have an important protective role in the respiratory epithelium and Zn
      deficiency may enhance airway inflammation and epithelial damage. The effects of
      mild nutritional Zn deficiency on airway hyperresponsiveness (AHR) and airway
      inflammation in mice sensitized and challenged with ovalbumin (OVA) to induce an
      allergic response were investigated. Balb/c mice were given Zn normal (ZN, 50
      mg/kg Zn) or Zn limited diets (ZL, 14 mg/kg Zn) before and during induction of
      allergic airway inflammation, with appropriate controls (saline-treated, SAL). ZL
      mice had greater levels of AHR than ZN mice, regardless of presence or absence of
      allergic inflammation. These mice also had increased eosinophilia and mucus cell
      hyperplasia compared with ZN mice. Second, ZN and ZL OVA-treated mice had
      significant decreases in airway epithelial Zinquin fluorescence, indicating a
      lowered availability of Zn compared with their SAL-treated counterparts. In
      contrast, the pro-apoptotic protein caspase-3, which was co-localized with Zn in
      the apical epithelium, was significantly increased in both ZN and ZL OVA-treated
      mice. Immunologically active caspase-3 and apoptosis were increased in OVA
      treated mice, especially the ZL group. These findings provide the first data for
      adverse effects of Zn deficiency on the respiratory epithelium and support a role
      for altered Zn homeostasis and caspase upregulation in asthma.

PMID- 12204891
TI  - Surfactant protein A decreases lung injury and mortality after murine marrow
      transplantation.
AB  - Surfactant protein A (SP-A), a collectin associated with surfactant lipids, can
      have immune modulatory effects. We hypothesized that exogenous and basal
      endogenous SP-A can function to suppress donor T-cell-dependent inflammation that
      occurs during the generation of idiopathic pneumonia syndrome after bone marrow
      transplantation (BMT). Wild-type and SP-A-deficient mice were conditioned with
      cyclophosphamide and lethal irradiation and then given allogeneic donor bone
      marrow plus inflammation-inducing spleen T cells. On Day 7 after BMT,
      bronchoalveolar lavage fluids from SP-A-deficient mice contained increased
      numbers of inflammatory cells and higher levels of proinflammatory mediators
      tumor necrosis factor-alpha, interferon-gamma, and nitric oxide than wild-type
      mice. Exaggerated inflammation in SP-A-deficient mice was associated with
      decreased dynamic lung compliance and increased donor T-cell-dependent mortality
      (P = 0.0007, n = 10). Nitrative stress in alveolar macrophages from SP-A(-/-)
      conditioned BMT recipients was higher than for SP-A(+/+) mice. Similarly, mice
      treated with transtracheal human SP-A (50 micro g), instilled on Day 4 after BMT
      during a time of in vivo donor T cell activation, exhibited decreased
      inflammation and improved early survival compared with buffer-instilled mice. We
      concluded that basal endogenous SP-A and enhanced alveolar SP-A level modulate
      donor T-cell-dependent immune responses and prolong survival after allogeneic
      BMT.

PMID- 12204892
TI  - Neuregulin-1 activates the JAK-STAT pathway and regulates lung epithelial cell
      proliferation.
AB  - Neuregulin-1 (NRG-1) is part of a family of proteins whose members are
      structurally related to epidermal growth factor. NRG-1 induces cell proliferation
      through a high-affinity receptor complex composed of a heterodimer of human
      epidermal growth factor-like receptor (HER) 2 and 3. In this study, we show that
      NRG-1 activates the Janus kinases (JAK) and signal transducer and activator of
      transcription proteins (STAT). NRG-1 induced a rapid and transient increase in
      tyrosine phosphorylation of TYK2 and JAK3, but not JAK1 or JAK2, and induced
      STAT3 and STAT5 tyrosine phosphorylation. Upon phosphorylation, STAT3
      translocated to the nucleus within 1 h. Activation of the JAK-STAT pathway was
      dependent on HER2/HER3 heterodimerization and was necessary for NRG-1-induced
      proliferation. Inhibition of HER2's ability to dimerize using the HER2-specific
      antibody 2C4 completely blocked NRG-1-induced JAK3, TYK2, STAT3, and STAT5
      tyrosine phosphorylation. Blocking the JAK-STAT pathway with a specific JAK-STAT
      pathway inhibitor, AG490, inhibited NRG-1-induced JAK and STAT phosphorylation
      and cell proliferation. These data suggest that NRG-1 activates the JAK-STAT
      signal transduction pathway through its high-affinity receptor, the HER2/HER3
      heterodimer. This pathway plays an important role in NRG-1-stimulated
      proliferation of pulmonary epithelial cells.

PMID- 12204893
TI  - Systemic pseudohypoaldosteronism from deletion of the promoter region of the
      human Beta epithelial na(+) channel subunit.
AB  - Systemic pseudohypoaldosteronism type I (PHAI) is an autosomal recessive disorder
      that arises from loss of function mutations of the alpha, beta, or gamma subunit
      of Epithelial Na(+) Channel (ENaC). In addition to a severe renal phenotype in
      the neonatal period, patients with PHAI develop a childhood pulmonary syndrome
      characterized by cough and frequent respiratory infections. We tested a patient,
      born to consanguineous parents, who presented with dehydration, metabolic
      acidosis, hyperkalemia, elevated renin and aldosterone levels at birth, and
      recurrent respiratory symptoms in his first year. He demonstrated defective
      epithelial Na(+) transport in multiple organs (raised sweat Cl(-), 120 mM; raised
      salivary Na(+) and Cl(-), 118 and 111 mM, respectively; and little nasal
      amiloride-sensitive potential difference). No deleterious mutation was identified
      in the coding region of the three ENaC subunits. Reverse transcriptase-polymerase
      chain reaction of nasal epithelial RNA showed reduced betaENaC expression, and
      inability to amplify promoter elements indicated the possibility of a deletion in
      the 5' region. Using a probe that corresponded to exon 1A of betaENaC, we
      confirmed a large deletion (> 1,300 bp). In summary, a homozygous mutation in the
      promoter region of betaENaC leads to PHAI, the first description of a mutation in
      the regulatory regions of an ENaC subunit leading to a clinical phenotype.

PMID- 12204894
TI  - Glucocorticoids inhibit lung cancer cell growth through both the extracellular
      signal-related kinase pathway and cell cycle regulators.
AB  - Glucocorticoids inhibit the proliferation of various cell types, but the
      mechanism of this inhibition remains unclear. We investigated the effect of
      dexamethasone on non-small cell lung cancer cell growth and cell cycle
      progression. We showed that dexamethasone suppresses the proliferation of A549
      and Calu-1 cells, with accumulation of cells in G1/G0 stage of the cell cycle, as
      determined by fluorescence-activated cell sorter analysis. Western blot analysis
      confirmed that this is associated with hypophosphorylation of retinoblastoma
      protein. Using Western blot analysis and in vitro kinase assays, we found that
      dexamethasone results in decreased activity of CDK2 and 4, decreased levels of
      cyclin D, E2F, and Myc, and increased levels of the CDK inhibitor p21(Cip1). In
      addition, we found that dexamethasone decreases activity of extracellular signal
      related kinase (ERK)/mitogen-activated protein kinase (MAPK). The kinetics of all
      these changes indicate that inhibition of the ERK/MAPK pathway precedes the cell
      cycle effects, suggesting that regulation of this MAPK-signaling pathway may be
      an alternative mechanism for glucocorticoid-induced cell cycle arrest and growth
      inhibition.

PMID- 12204895
TI  - The role of mitogen-activated protein kinases in eotaxin-induced cytokine
      production from bronchial epithelial cells.
AB  - Eotaxin is a critical chemokine eliciting migration of eosinophils and basophils
      in the pathogenesis of bronchial asthma. Recent studies have shown that the
      specific receptor for eotaxin, CCR3, is expressed in bronchial epithelial cells.
      Although mitogen-activated protein (MAP) kinases are involved in diverse cell
      functions of bronchial epithelial cells, their role in eotaxin signaling is
      unknown. In this study, we studied the activation and functional relevance of MAP
      kinases in bronchial epithelial cells stimulated with eotaxin. Eotaxin (1-100 nM)
      induced tyrosine/threonine phosphorylation and activation of extracellular
      regulated kinase (ERK) 1/2 and p38 in NCI-H(292) cells and normal human bronchial
      epithelial cells. The phosphorylation of these MAP kinases was detectable after
      30 s, and peaked at 5 min. Eotaxin stimulated production of interleukin-8 and
      granulocyte macrophage colony-stimulating factor. Pretreatment of Compound X (a
      specific CCR3 antagonist), pertussis toxin, genistein, and wortmannin reduced the
      MAP kinase phosphorylation and cytokine production. The eotaxin-induced cytokine
      production was inhibited by specific inhibitors for MAP/ERK kinase (PD98059) and
      p38 MAP kinase (SB202190). These results suggest that both ERK1/2 and p38 MAP
      kinase activated by eotaxin have a critical role in the pathogenesis of asthma.

PMID- 12204896
TI  - Insulin-like growth factor-I inhibits cell growth in the a549 non-small lung
      cancer cell line.
AB  - Insulin-like growth factors (IGFs) are potent mitogenic and antiapoptotic factors
      for many cell types, including some normal and neoplastic lung cells in vitro.
      However, in this study we show that IGF-I, at concentrations of 10 ng/ml or
      greater, significantly inhibits DNA synthesis and cell proliferation in a human
      lung adenocarcinoma cell line, A549. Inhibition of DNA synthesis was completely
      reversed by an IGF-I receptor-neutralizing antibody, alphaIR-3, indicating that
      IGF-I receptor activation is involved in its inhibitory effect. Attenuation of
      the p44/42 mitogen-activated protein kinase (MAPK) and phosphatidylinositol 3'
      kinase (PI 3'-kinase) pathways downstream of the IGF-I receptor using the
      inhibitors PD98059 and LY294002, respectively, partially reversed IGF-I-induced
      inhibition. Acute (2-60 min) and chronic (24 h) exposure of A549 cells to 100
      ng/ml IGF-I resulted in sustained phosphorylation of Akt/protein kinase B
      downstream of PI 3'-kinase, whereas p44/42 MAPK phosphorylation was decreased in
      response to chronic exposure to IGF-I. An IGF-I dose-dependent increase in the
      cyclin-dependent kinase inhibitor p21(Cip1/WAF1) was also observed over 24 h of
      treatment. Collectively, these data suggest that IGF-I is growth inhibitory to
      A549 cells, possibly via sustained activation of the PI 3'-kinase signaling
      pathway, and induction of p21(Cip1/WAF1).

PMID- 12204897
TI  - Heparin inhibits DNA synthesis and gene expression in alveolar type II cells.
AB  - Responses of isolated type II alveolar cells to fibroblast growth factors (FGF)
      have been shown to be sensitive to the level of sulfation in extracellular matrix
      (ECM) substrata. These observations may reflect the specific in situ distribution
      and level of sulfation of ECM within the alveolar basement membranes (ABM)
      associated with type II cells. The goal of this study was to determine if the
      model sulfated ECM heparin modified DNA synthesis and gene expression by type II
      cells in a concentration dependent-manner. Isolated rat type II cells were
      exposed to different concentrations of heparin (0.005-500 micro g/ml) in serum
      free medium for 1-3 d with or without FGF-1 or FGF-2. The effects of heparin were
      examined by [(3)H]thymidine incorporation into DNA, total cell protein, cell
      number, and selected gene expression. Results indicated that heparin inhibited
      [(3)H]thymidine uptake in a concentration-dependent manner. Total protein, cell
      number, and FGF-2 protein expression and mRNA of FGF-1, -2, and FGF receptor-2
      detected by reverse transcriptase-polymerase chain reaction were decreased by
      heparin. These results demonstrate that sulfated molecules in the ABM may play
      important regulatory role(s) in selected type II cell activities during normal
      cell homeostasis, turnover, and repair after lung injury.

PMID- 12204898
TI  - Surfactant protein a inhibits lipopolysaccharide-induced immune cell activation
      by preventing the interaction of lipopolysaccharide with lipopolysaccharide
      binding protein.
AB  - Pulmonary surfactant protein (SP)-A, an innate immune molecule, modifies
      lipopolysaccharide (LPS)-induced cell responses. Because SP-A avidly binds to the
      deep rough (Re) mutant of LPS, we first investigated the functional consequences
      of this interaction and found that preincubation of Re-LPS with SP-A
      significantly and in a dose-dependent manner decreased the sensitivity of rat
      alveolar macrophages and human mononuclear cells to Re-LPS-induced activation at
      limited amounts of LPS-binding protein (LBP). At high LBP concentrations, the SP
      A-mediated cellular inhibition of Re-LPS-induced activation was abrogated.
      Because LBP-catalyzed binding of LPS to CD14 is essential for low-dose LPS
      induced signaling, we then hypothesized that SP-A inhibits Re-LPS-induced immune
      cell activation via inhibiting the binding of Re-LPS to LBP. Binding competition
      experiments employing a surface plasmon resonance technique showed that Re-LPS
      preincubated with SP-A bound to LBP to a significantly lesser extent than Re-LPS
      alone. For enhanced cellular association of [(3)H]LPS/SP-A complexes to occur,
      the expression of membrane-bound CD14 by human embryonic kidney cells 293 was not
      essential. Therefore, the ability of SP-A to inhibit immune cell activation by Re
      LPS may be due to its ability to block the binding of Re-LPS to LBP and prevent
      the initiation of the LBP/CD14 pathway for inflammatory reactions in the lung.

PMID- 12204899
TI  - Increased glucocorticoid receptor Beta expression converts mouse hybridoma cells
      to a corticosteroid-insensitive phenotype.
AB  - Glucocorticoid (GC) insensitivity is a challenging clinical problem associated
      with many chronic inflammatory disorders and life-threatening disease
      progression. The molecular basis of GC insensitivity, however, is unknown.
      Alternative splicing of the GC receptor (GCR) pre-mRNA generates a second GCR,
      termed GCRbeta, which does not bind GC but antagonizes the transactivating
      activity of the classic GCR, termed GCRalpha. GC-insensitive conditions have been
      associated with increased GCRbeta expression. Whether or not increased GCRbeta
      expression can contribute to GC insensitivity, however, remains controversial. To
      more precisely demonstrate the effect of GCRbeta on steroid responsiveness, we
      virally transduced GCRbeta cDNA into mouse DO-11.10 hybridoma cells, as mice are
      known to be deficient in the GCRbeta gene. We demonstrate that viral transduction
      of GCRbeta cDNA into mouse hybridoma cells to induce stable expression of GCRbeta
      results in GC insensitivity of these cells. Furthermore, in such cells GCRalpha
      is complexed with GCRbeta. Such heterodimer formation may account for the reduced
      effectiveness of GC action in cells overexpressing GCRbeta.

PMID- 12204900
TI  - Acute cigarette smoke-induced connective tissue breakdown requires both
      neutrophils and macrophage metalloelastase in mice.
AB  - The cells/proteases responsible for the development of smoke-induced emphysema is
      an area of intense investigation. Mice with knockout of macrophage
      metalloelastase genes (MME(-/-)) do not develop emphysema after smoke exposure,
      but we also observed that neutrophils (PMN) in lavage appeared to be a
      requirement for acute connective tissue breakdown. In this study we exposed mice
      to cigarette smoke and examined lavage PMN, macrophages (MAC), desmosine (DES, a
      measure of elastin breakdown) and hydroxyproline (HP, a measure of collagen
      breakdown) 24 h afterwards. MME(+/+) mice exposed to smoke showed elevations in
      PMN, DES, and HP, but no elevations were seen in MME-deficient mice. Both PMN
      influx and increased levels of DES/HP could be restored by administering MAC from
      MME(+/+) mice to MME-deficient mice and then exposing them to smoke. RS113456, a
      metalloprotease inhibitor, also prevented PMN influx and connective tissue
      breakdown. Western blots against mouse alpha(1)-antitrypsin (alpha(1)AT) showed
      that alpha(1)AT was not protected in MME-deficient mice, nor by administration of
      RS113456. We conclude that, in mice, acute smoke-induced connective tissue
      breakdown, the precursor to emphysema, requires both PMN and MME, that PMN influx
      appears to be secondary to MAC activation, and that this process initially does
      not involve protection of alpha(1)AT from metalloprotease attack.

PMID- 12204901
TI  - PGD(2) modulates fibroblast-mediated native collagen gel contraction.
AB  - Repair of tissues is a necessary step in restoring tissue function following
      injury consequent to inflammation. Many inflammatory mediators are capable of
      modulating not only the activity of "inflammatory cells" but also of modulating
      functions of parenchymal cells that may contribute to repair. Disordered repair
      is believed to contribute to tissue dysfunction in many inflammatory diseases,
      including bronchial asthma. The current study evaluated the ability of
      prostaglandin D(2) (PGD(2)) to modulate fibroblast repair using the in vitro
      contraction of three-dimensional native collagen gels as a model system. PGD(2)
      stimulated gel contraction in a concentration- and time-dependent manner. In
      contrast, the PGD(2) analog BW245C inhibited contraction. Both effects were
      blocked by a DP-receptor blocker (AH6809). Neither TP receptor blocker SQ29548
      nor protein kinase (PK) A antagonist KT5720 hand an effect on PGD(2)-stimulated
      contraction, suggesting action through a novel prostaglandin D receptor. PKC
      inhibitor calphostin-C (10(-6) M) blocked the PGD(2) stimulation of gel
      contraction. A calcium-independent PKC-epsilon inhibitor (Ro31-8220), but not
      calcium-dependent PKC-alpha and -beta inhibitors, also blocked the PGD(2) effect
      on contraction, implying a role for a calcium-independent pathway. This study,
      therefore, supports a role for PGD(2) in tissue repair and remodeling. These
      effects of PGD(2) appear to be mediated through receptor-signal transduction
      pathways different from the cAMP-PKA pathways mediating the proinflammatory
      activity of PGD(2), creating the possibility for selective therapeutic
      manipulation.

PMID- 12204918
TI  - Global burden of depressive disorders: the issue of duration.

PMID- 12204919
TI  - Clozapine-resistant schizophrenia: a positive approach.

PMID- 12204920
TI  - Post-streptococcal autoimmune psychiatric and movement disorders in children.

PMID- 12204921
TI  - Suicide among the elderly: the promise of telecommunications.

PMID- 12204922
TI  - Fatal and non-fatal repetition of self-harm. Systematic review.
AB  - BACKGROUND: Non-fatal self-harm frequently leads to non-fatal repetition and
      sometimes to suicide. We need to quantify these two outcomes of self-harm to help
      us to develop and test effective interventions. AIMS: To estimate rates of fatal
      and non-fatal repetition of self-harm. METHOD: A systematic review of published
      follow-up data, from observational and experimental studies. Four electronic
      databases were searched and 90 studies met the inclusion criteria. RESULTS:
      Eighty per cent of studies found were undertaken in Europe, over one-third in the
      UK. Median proportions for repetition 1 year later were: 16% non-fatal and 2%
      fatal; after more than 9 years, around 7% of patients had died by suicide. The UK
      studies found particularly low rates of subsequent suicide. CONCLUSIONS: After 1
      year, non-fatal repetition rates are around 15%. The strong connection between
      self-harm and later suicide lies somewhere between 0.5% and 2% after 1 year and
      above 5% after 9 years. Suicide risk among self-harm patients is hundreds of
      times higher than in the general population.

PMID- 12204923
TI  - Beds, budgets and burdens: learning disability expenditure v. workload across
      English health authorities. Comparative review.
AB  - BACKGROUND: Following the closure of asylums and widespread changes in the
      population distribution of people with learning disabilities, there has been
      little investigation of changing expenditure requirements of health authorities
      in England. AIMS: To compare expenditure on learning disability health services
      across England with the burden of services regionally, as estimated by numbers of
      people with learning disabilities. METHOD: A national database was set up using
      data from the National Audit Commission and the Department of Health. The
      spend/burden ratio was calculated and correlation tests for likely causes of
      inequality were applied. RESULTS: There is widespread discrepancy from the median
      spend/burden ratio of 10,260 UK pounds per person with learning disability. There
      is a positive correlation between ratios and levels of net exports of people
      funded by their local authority social services to reside "out of area".
      Comparative underspending occurs in rural areas. CONCLUSIONS: There are
      inequalities in levels of spending on learning disability services. Comparison of
      regions suggests resources may not be allocated fairly. Health authorities should
      ensure that population increases are mirrored by appropriate adjustments in
      expenditure.

PMID- 12204924
TI  - Duration of major depressive episodes in the general population: results from The
      Netherlands Mental Health Survey and Incidence Study (NEMESIS).
AB  - BACKGROUND: Data on the duration of major depressive episodes (MDE) in the
      general population are sparse. AIMS: To assess the duration of MDE and its
      clinical and socio-demographic determinants in a study group drawn from the
      general population with newly originated episodes of major depression. METHOD:
      The Netherlands Mental Health Survey and Incidence Study is a prospective
      epidemiological survey in the adult population (n=7076), using the Composite
      International Diagnostic Interview. Duration of MDE over 2 years was assessed
      with a Life Chart Interview. RESULTS: The median duration of MDE was 3.0 months;
      50% of participants recovered within 3 months, 63% within 6 months, 76% within 12
      months and nearly 20% had not recovered at 24 months. Determinants of persistence
      were severity of depression and comorbid dysthymia. A recurrent episode predicted
      shorter duration. CONCLUSIONS: Although half of those affected with MDE recovered
      rapidly, the risk of chronicity (duration 24 months or more) was considerable.
      This underlines the necessity of diagnosing and treating those at risk.

PMID- 12204925
TI  - Prevalence of psychiatric disorder and the need for psychiatric care in Northern
      Ireland. Population study in the District of Derry.
AB  - BACKGROUND: This is the first report on the epidemiology of psychiatric disorders
      and needs for psychiatric treatment in the District of Derry, Northern Ireland.
      AIMS: To assess the prevalence of psychiatric disorder and the needs for
      treatment in the general population of Derry. METHOD: The sample was drawn at
      random with a two-phase design using the General Health Questionnaire (GHQ-28)
      during the first phase, and the Schedules for Clinical Assessment in
      Neuropsychiatry (SCAN) with the Needs for Care Assessment (NFCAS-C) in the second
      phase. RESULTS: The second phase (n=307) gave a weighted 1-month prevalence of
      hierarchically ordered ICD-10 psychiatric disorders of 7.5% and a 1-year
      prevalence of 12.2%. The equivalent prevalences for depressive disorders were
      2.4% and 6.0%, respectively, and those for anxiety states were 3.5% and 3.7%.
      Only a quarter of needs for treatment were met, with the situation being better
      for depression than for anxiety. CONCLUSIONS: The rates of psychiatric disorder
      in Derry were even higher than those reported by a similar survey in inner
      London. This almost certainly reflects the very high levels of social deprivation
      in the District. Needs for treatment were often unmet.

PMID- 12204926
TI  - Residential care in Italy. National survey of non-hospital facilities.
AB  - BACKGROUND: In Italy, where all mental hospitals have been gradually phased out
      since 1978, psychiatric patients requiring long-term care are being treated in
      non-hospital residential facilities (NHRFs). However, detailed data on these
      facilities are sparse. AIMS: The Progetto Residenze (PROGRES) residential care
      project is a three-phase study, the first phase of which aims to survey the main
      characteristics of all Italian NHRFs. METHOD: Structured interviews were
      conducted with the manager of each NHRF. RESULTS: On 31 May 2000 there were 1370
      NHRFs with 17 138 beds; an average of 12.5 beds each and a rate of 2.98 beds per
      10 000 inhabitants. Residential provision varied ten-fold between regions and
      discharge rates were very low. Most had 24-hour staffing with 1.42 patients per
      full-time worker. CONCLUSIONS: There is marked variability in the provision of
      residential places between different regions; discharge rates are generally low.

PMID- 12204927
TI  - Suicide among the elderly: the long-term impact of a telephone support and
      assessment intervention in northern Italy.
AB  - BACKGROUND: Previous short-term work reported fewer suicides among elderly users
      of a telephone helpline and emergency response service (the TeleHelp-TeleCheck
      Service). AIMS: To examine long-term effects of the service on suicide in an
      elderly population of northern Italy. METHOD: The service provided twice-weekly
      support and needs assessment telephone calls and a 24h emergency alarm service.
      Data from 1988 to 1998 allowed comparison of 18 641 service users with a
      comparable general population group of the Veneto region in Italy. RESULTS:
      Significantly fewer suicide deaths (n(OBSERVED)=6) occurred among elderly service
      users (standardised mortality ratio (SMR) 28.8%) than expected
      (n(EXPECTED)=20.86; chi(2)=10.58, d.f.=1, P<0.001) despite an assumed
      overrepresentation of persons at increased risk. The service performed well for
      elderly females (n(OBSERVED)=2, SMR=16.6%, n(EXPECTED)=12.03; chi(2)=8.36,
      d.f.=1, P<0.001). CONCLUSIONS: The study confirms the initial promise of the
      TeleHelp-TeleCheck service over a much longer time period. Further research will
      clarify the apparent lack of benefit for elderly males.

PMID- 12204928
TI  - Self-help for bulimic disorders: a randomised controlled trial comparing minimal
      guidance with face-to-face or telephone guidance.
AB  - BACKGROUND: There is great potential demand for treatment of bulimia nervosa and
      binge eating disorder. Skilled therapists are in short supply. Self-help and
      guided self-help based upon books have shown some promise as an economical
      alternative to full therapy in some cases. AIMS: To investigate the efficacy and
      effectiveness of self-help with and without guidance in a specialist secondary
      service. METHOD: A randomised controlled trial comparing three forms of self-help
      over 4 months with a waiting-list comparison group and measurement of service
      consumption over the subsequent 8 months. RESULTS: Self-help delivered with four
      sessions of face-to-face guidance led to improved outcome over 4 months. There is
      also some evidence to support the use of telephone guidance. A minority of
      participants achieved lasting remission of their disorder in relation to self
      help, but there was no significant difference in final outcome between the groups
      after they had progressed through the stepped care programme. Patients initially
      offered guided self-help had a lower long-term drop-out rate. CONCLUSIONS: Guided
      self-help is a worthwhile initial response to bulimia nervosa and binge eating
      disorder. It is a treatment that could be delivered in primary care and in other
      non-specialist settings.

PMID- 12204929
TI  - Exposure to case management: relationships to patient characteristics and
      outcome. Report from the UK700 trial.
AB  - BACKGROUND: Trials in community psychiatry must balance rigour with
      generalisability. The UK700 trial failed to find a significant effect on
      hospitalisation, but its sample population contained significant heterogeneity of
      exposure to case management in the two groups. AIMS: To test whether patients
      successfully exposed to a minimum of 12 months' intensive case management over
      the 2-year follow-up period achieved reduced hospitalisation. METHOD: Of 679
      participants with hospitalisation data, 84 were identified as having < 12 months'
      exposure owing to prolonged hospitalisation, imprisonment or a combination of the
      two. These patients were excluded and outcomes tested for the remaining 595
      patients. RESULTS: Overall reduced case-load size did not reduce hospitalisation
      or treatment costs over 2 years despite elimination of outliers. Age, previous
      hospitalisation and source of recruitment to the study all correlated with
      outcome. CONCLUSIONS: Case-load reduction is not in itself enough to reduce the
      need for hospital care in psychosis. Baseline patient characteristics (in
      particular length of previous hospitalisation and recruitment from in-patient
      care) have a significant influence and should be allowed for in power
      calculations. Identifying the optimal clinical profile for patients likely to
      benefit from intensive case management remains a pressing need for further
      studies.

PMID- 12204930
TI  - Neuroticism as a predictor of mood change: the effects of tryptophan depletion.
AB  - BACKGROUND: Acute tryptophan depletion (ATD) results in a transient lowering of
      mood in patients recovered from depression and in healthy volunteers with a
      family history of affective disorders. The personality trait of neuroticism is
      strongly associated with depression. AIMS: To assess whether neuroticism predicts
      mood change in response to ATD in healthy volunteers. METHOD: Healthy volunteers
      who scored at the top and bottom fifth percentiles of neuroticism scores (17 and
      15 respectively) were selected. In a double-blind, crossover study they received
      a tryptophan-free or a control drink. Mood and cognition were assessed. RESULTS:
      Neuroticism did not predict the amount of mood change following ATD but did
      moderate performance on the verbal fluency test. A family history of affective
      disorder (n=5) predicted mood change but not cognitive function following ATD.
      CONCLUSIONS: Neuroticism moderates aspects of cognitive function, but in this
      study it was not strongly related with mood change via serotonin.

PMID- 12204931
TI  - Predictors of response to treatment for chronic fatigue syndrome.
AB  - BACKGROUND: Controlled trials have shown that psychological interventions
      designed to encourage graded exercise can facilitate recovery from chronic
      fatigue syndrome. AIMS: To identify predictors of response to psychological
      treatment for chronic fatigue syndrome. METHOD: Of 114 patients assigned to
      equally effective treatment conditions in a randomised, controlled trial, 95
      completed follow-up assessments. Relationships between variables measured prior
      to randomisation and changes in physical functioning and subjective handicap at 1
      year were evaluated by multiple regression. RESULTS: Poor outcome was predicted
      by membership of a self-help group, being in receipt of sickness benefit at the
      start of treatment, and dysphoria as measured by the Hospital Anxiety and
      Depression scale. Severity of symptoms and duration of illness were not
      predictors of response. CONCLUSIONS: Poor outcome in the psychological treatment
      of chronic fatigue syndrome is predicted by variables that indicate resistance to
      accepting the therapeutic rationale, poor motivation to treatment adherence or
      secondary gains from illness.

PMID- 12204932
TI  - Compensation claims after whiplash neck injury.

PMID- 12204933
TI  - Forget community care--reinstitutionalisation is here.

PMID- 12204934
TI  - Regional selectivity of novel antipsychotics.

PMID- 12204935
TI  - Compensation claims after whiplash neck injury.

PMID- 12204936
TI  - Measuring amygdala volume.

PMID- 12204937
TI  - Phenomenology of acute confusional states.

PMID- 12204938
TI  - Psychiatry in China.

PMID- 12204939
TI  - One hundred years ago: amaurotic family idiocy. Lancet, 23 August 1902, p. 519.

PMID- 12204942
TI  - Biological and clinical significance of lipids as modulators of immune system
      functions.

PMID- 12204944
TI  - Peripheral blood lymphocyte subsets in adolescents: a longitudinal analysis from
      the REACH project.
AB  - Flow cytometry analysis of lymphocyte subset markers was performed for a group of
      sexually active, human immunodeficiency virus (HIV)-negative adolescents over a 2
      year period to establish normative data. Data were collected in the REACH Project
      (Reaching for Excellence in Adolescent Care and Health), a multicenter,
      longitudinal study of HIV-positive and high-risk HIV-negative adolescents. Two-
      and three-color flow cytometry data were collected every 6 months for these
      subjects. We determined the effects of gender, race, and age on the following
      lymphocyte subset markers: total CD4(+) cells, CD4(+) naive cells, CD4(+) memory
      cells, all CD8(+) cells, CD8(+) naive cells, CD8(+) memory cells, CD16(+) natural
      killer cells, and CD19(+) B cells. Gender was the demographic characteristic most
      frequently associated with differences in lymphocyte subset measures. Females had
      higher total CD4(+) cell and CD4(+) memory cells counts and lower CD16(+) cell
      counts than males. Age was associated with higher CD4(+) memory cell counts as
      well as higher CD8(+) memory cell counts. For CD19(+) cells, there was an
      interaction between age and gender, with males having significantly lower CD19(+)
      cell counts with increasing age, whereas there was no age effect for females.
      Race and/or ethnicity was associated with differences in total CD8(+) cell counts
      and CD8(+) memory cell counts, although both of these associations involved an
      interaction with gender.

PMID- 12204943
TI  - Laboratory diagnosis of visceral leishmaniasis.

PMID- 12204945
TI  - Active surveillance for scrapie by third eyelid biopsy and genetic susceptibility
      testing of flocks of sheep in Wyoming.
AB  - Control of scrapie, an ovine transmissible spongiform encephalopathy or prion
      disorder, has been hampered by the lack of conventional antemortem diagnostic
      tests. Currently, scrapie is diagnosed by postmortem examination of the brain and
      lymphoid tissues for PrP(Sc), the protein marker for this group of disorders. For
      live, asymptomatic sheep, diagnosis using tonsil or third-eyelid lymphoid tissue
      biopsy and PrP(Sc) assay has been described. To evaluate the feasibility and
      efficacy of third-eyelid testing for identification of infected flocks and
      individual infected sheep, 690 sheep from 22 flocks were sampled by third-eyelid
      lymphoid tissue biopsy and immunohistochemistry. Sheep were further evaluated for
      relative genetic susceptibility and potential contact exposure to scrapie. Third
      eyelid testing yielded suitable samples for 80% of the sheep tested, with a mean
      of 18.1 lymphoid follicles (germinal centers) per histologic section. Three
      hundred eleven of the sheep were sampled through passive surveillance programs,
      in which only sheep with potential contact with an infected sheep at a lambing
      event were tested, regardless of their scrapie susceptibility genotype. In
      addition, 141 genetically susceptible sheep with no record of contact with an
      infected animal at a lambing event were sampled through a targeted active
      surveillance program. Ten PrP(Sc)-positive sheep were identified through the
      passive surveillance program, and an additional three PrP(Sc)-positive sheep,
      including two from flocks with no history of scrapie, were identified through the
      active surveillance program. All PrP(Sc)-positive sheep had the highly
      susceptible PrP genotype. Third-eyelid testing is a useful adjunct to flock
      monitoring programs, slaughter surveillance, and mandatory disease reporting in a
      comprehensive scrapie eradication and research program.

PMID- 12204946
TI  - Augmentation of the lipopolysaccharide-neutralizing activities of human
      cathelicidin CAP18/LL-37-derived antimicrobial peptides by replacement with
      hydrophobic and cationic amino acid residues.
AB  - Mammalian myeloid and epithelial cells express various peptide antibiotics (such
      as defensins and cathelicidins) that contribute to the innate host defense
      against invading microorganisms. Among these peptides, human cathelicidin
      CAP18/LL-37 (L(1) to S(37)) possesses not only potent antibacterial activity
      against gram-positive and gram-negative bacteria but also the ability to bind to
      gram-negative lipopolysaccharide (LPS) and neutralize its biological activities.
      In this study, to develop peptide derivatives with improved LPS-neutralizing
      activities, we utilized an 18-mer peptide (K(15) to V(32)) of LL-37 as a template
      and evaluated the activities of modified peptides by using the CD14(+) murine
      macrophage cell line RAW 264.7 and the murine endotoxin shock model. By
      replacement of E(16) and K(25) with two L residues, the hydrophobicity of the
      peptide (18-mer LL) was increased, and by further replacement of Q(22), D(26),
      and N(30) with three K residues, the cationicity of the peptide (18-mer LLKKK)
      was enhanced. Among peptide derivatives, 18-mer LLKKK displayed the most powerful
      LPS-neutralizing activity: it was most potent at binding to LPS, inhibiting the
      interaction between LPS and LPS-binding protein, and attaching to the CD14
      molecule, thereby suppressing the binding of LPS to CD14(+) cells and attenuating
      production of tumor necrosis factor alpha (TNF-alpha) by these cells.
      Furthermore, in the murine endotoxin shock model, 18-mer LLKKK most effectively
      suppressed LPS-induced TNF-alpha production and protected mice from lethal
      endotoxin shock. Together, these observations indicate that the LPS-neutralizing
      activities of the amphipathic human CAP18/LL-37-derived 18-mer peptide can be
      augmented by modifying its hydrophobicity and cationicity, and that 18-mer LLKKK
      is the most potent of the peptide derivatives, with therapeutic potential for
      gram-negative bacterial endotoxin shock.

PMID- 12204947
TI  - Impaired macrophage phagocytosis of apoptotic neutrophils in patients with human
      immunodeficiency virus type 1 infection.
AB  - Dysfunction of neutrophils (polymorphonuclear leukocytes [PMNL]) and macrophagic
      cells occurs as a consequence of human immunodeficiency virus type 1 (HIV-1)
      infection. Macrophages contribute to the resolution of early inflammation
      ingesting PMNL apoptotic bodies. This study investigated macrophage ability to
      phagocytose PMNL apoptotic bodies in patients with HIV-1 infection in comparison
      with uninfected individuals and the effect of HIV Nef protein on apoptotic body
      phagocytosis to determine if phagocytic activity is impaired by HIV infection.
      Monocytes/macrophages were isolated from 10 HIV-1-infected patients and from five
      healthy volunteers, whereas PMNL were isolated from healthy volunteers.
      Macrophage phagocytosis of apoptotic PMNL was determined by staining of apoptotic
      bodies with fluorescein-conjugated concanavalin A or with fluorescein-labeled
      phalloidin. Our data show significant impairment of PMNL apoptotic body
      macrophage phagocytosis in subjects with HIV-1 infection presenting a
      concentration of CD4(+) T lymphocytes of >200/mm(3) and in particular in those
      with <200 CD4(+) T lymphocyte cells/mm(3). In addition, HIV-1 recombinant Nef
      protein is able to decrease phagocytosis of apoptotic PMNL from normal human
      macrophages in a dose-dependent manner. The results of our study suggest that
      impaired macrophage phagocytosis of PMNL apoptotic bodies may contribute to the
      persistence of the inflammatory state in HIV-infected subjects, especially during
      opportunistic infections that are often favored by defective phagocytic activity.

PMID- 12204948
TI  - Evaluation of an in-house-developed radioassay kit for antibody detection in
      cases of pulmonary tuberculosis and tuberculous meningitis.
AB  - A radioassay for the detection of antitubercular antibody has been developed. The
      technique involves the addition of (125)I-labeled Mycobacterium tuberculosis
      antigen as a tracer, diluted clinical sample (serum or cerebrospinal fluid
      [CSF]), and heat-inactivated Staphylococcus aureus to capture the antibody,
      incubation for 4 h, and quantitation of the amount of antibody present in the
      sample. A total of 330 serum samples from patients with pulmonary tuberculosis
      and 138 control serum samples from individuals who were vaccinated with M. bovis
      BCG and from patients with pulmonary disorders of nontubercular origin were
      analyzed. Also, 26 CSF samples from patients with tuberculous meningitis and 24
      CSF samples as controls from patients with central nervous system disorders of
      nontuberculous origin were analyzed. Sensitivities of 80 and 73% were observed
      for patients with pulmonary tuberculosis and tuberculous meningitis,
      respectively, and specificities of 90 and 88% were seen for the two groups of
      patients, respectively. The sensitivity was lower, however, for human
      immunodeficiency virus-infected patients coinfected with M. tuberculosis. The
      control population could be differentiated from the patient population. This
      assay is rapid and user friendly and, with its good sensitivity and specificity,
      should benefit the population by providing diagnoses early in the course of
      disease and, hence, permit the early administration of appropriate chemotherapy.

PMID- 12204949
TI  - Functional and phenotypic changes in circulating lymphocytes from hospitalized
      zambian children with measles.
AB  - Measles is associated with immunosuppression and increased susceptibility to
      secondary infections and is a particular problem in developing countries.
      Lymphocyte changes accompanying immune activation and regulation of the immune
      response may contribute to immunosuppression. To evaluate lymphocyte changes
      during measles, children (n = 274) hospitalized with measles in Lusaka, Zambia,
      were evaluated at entry, discharge, and 1-month follow-up and compared to healthy
      Zambian children (n = 98). Lymphopenia was present on hospital admission and
      reflected decreased CD4 and CD8 T cells but resolved quickly. Lymphopenia was
      most marked in girls, in those with temperatures of >38.5 degrees C, and in
      malnourished children. CD4/CD8 ratios were decreased at all time points and were
      lower in boys than in girls at discharge and follow-up. Spontaneous death
      occurred in cultured lymphocytes, and the proportions of freshly isolated cells
      undergoing apoptosis, based on annexin V and propidium iodide staining, were
      increased. Surface Fas was increased on both CD4 and CD8 T cells compared to
      controls, and expression was greater on CD4 T cells and was inversely correlated
      with lymphocyte viability in culture at study entry. Mitogen stimulation of
      lymphocytes improved viability, but inhibitors of Fas, tumor necrosis factor
      (TNF)-related apoptosis-inducing ligand, and TNF did not. Plasma levels of
      beta(2) microglobulin and soluble Fas, Fas ligand, CD8, CD4, and TNF receptor
      were increased, and soluble CD8 was higher in boys than in girls. The multiple
      effects of measles on lymphocytes from Zambian children include decreased numbers
      in circulation, increased activation, and increased susceptibility to cell death,
      with substantive differences in the magnitude of these changes between boys and
      girls.

PMID- 12204950
TI  - Comparison of in-house and commercial slides for detection by immunofluorescence
      of immunoglobulins G and M against Bartonella henselae and Bartonella quintana.
AB  - We compared the sensitivities and specificities of indirect fluorescent antibody
      tests developed in our laboratory and commercially available from Focus
      Technologies (FT; formerly MRL Diagnostic) for detection of serum antibodies to
      Bartonella spp. Serum samples tested were from patients with culture- or PCR
      confirmed Bartonella quintana or B. henselae infections causing cat scratch
      disease (CSD), chronic bacteremia, or endocarditis. At a cutoff titer of 64, the
      FT test had higher sensitivity than our in-house test in detecting anti-B.
      henselae immunoglobulin G (IgG) antibodies in CSD patients (91.2 versus 52.9%; P
      < 0.001). The specificity in serum samples from 85 control patients was, however,
      lower with the FT test (87%) than with the in-house test (98.8%) (P = 0.002). A
      cutoff titer of 128 improves the specificity for the FT test but lowers the
      sensitivity to 85%. For patients infected with B. henselae, our in-house test,
      but not the FT test, enabled endocarditis to be detected more reliably. With the
      in-house test, titers of IgG against B. henselae of >/=1,024 were found only in
      endocarditis patients and not in CSD patients. With the FT test, 19.1% of CSD
      patients had titers of IgG against B. henselae of >/=1,024 (P < 0.001). Our in
      house technique also improved detection of anti-B. quintana antibodies in
      homeless patients with endocarditis. IgG titers of >/=1,024 were present in 75%
      of serum samples, but only in 16.7% of serum samples with the FT test (P =
      0.004). Since each test has advantages over the other, the serological diagnosis
      of Bartonella infections would benefit if both tests were used concurrently.

PMID- 12204952
TI  - Comparison between the skin snip test and simple dot blot assay as potential
      rapid assessment tools for Onchocerciasis in the postcontrol era in Ghana.
AB  - Successful control of onchocerciasis through mass distribution of ivermectin
      needs to be coupled with reliable, sensitive, specific, yet affordable diagnostic
      methods to monitor and ensure the efficacy of such measures. The effort put into
      the development of diagnostic methods for onchocerciasis that can substitute for
      or work in combination with the present "gold standard," the skin snip test, has
      resulted in the discovery of a number of immunogenic proteins with potential use
      as diagnostic tools in the postcontrol era. Most of these proteins have now been
      produced through recombinant DNA techniques. However, when costs are not a
      trivial issue, none of them have yet found their way into the areas where the
      disease still exists. In the present study, we have evaluated the performance of
      a simple dot blot assay which uses a mixture of native proteins designated PakF
      as a serious contender in the quest for a less invasive and more sensitive method
      to detect Onchocerca volvulus infection in areas with diverse endemicities. Our
      results indicate that the assay we propose is more sensitive than the skin snip
      test and shows high specificity, both characteristics required for a suitable
      tool for the monitoring of onchocerciasis in the postcontrol era.

PMID- 12204951
TI  - Antibody responses of cattle with respiratory coronavirus infections during
      pathogenesis of shipping fever pneumonia are lower with antigens of enteric
      strains than with those of a respiratory strain.
AB  - The serum antibody responses of cattle with respiratory coronavirus infections
      during the pathogenesis of shipping fever pneumonia were analyzed with different
      bovine coronavirus antigens, including those from a wild-type respiratory bovine
      coronavirus (RBCV) strain (97TXSF-Lu 15-2) directly isolated from lung tissue
      from a fatally infected bovine, a wild-type enteropathogenic bovine coronavirus
      (EBCV) strain (Ly 138-3), and the highly cell culture-adapted, enteric prototype
      strain (EBCV L9-81). Infectivity-neutralizing (IN) and hemagglutinin-inhibiting
      (HAI) activities were tested. Sequential serum samples, collected during the
      onset of the respiratory coronavirus infection and at weekly intervals for 5
      weeks thereafter, had significantly higher IN and HAI titers for antigens of RBCV
      strain 97TXSF-Lu15-2 than for the wild-type and the highly cell culture-adapted
      EBCV strains, with P values ranging from <0.0001 to 0.0483. The IN and HAI
      antibody responses against the two EBCV strains did not differ significantly, but
      the lowest titers were detected with EBCV strain L9-81.

PMID- 12204953
TI  - Calcium phosphate nanoparticles induce mucosal immunity and protection against
      herpes simplex virus type 2.
AB  - Previously we reported that calcium phosphate nanoparticles (CAP) represented a
      superior alternative to alum adjuvants in mice immunized with viral protein.
      Additionally, we showed that CAP was safe and elicited no detectable
      immunoglobulin E (IgE) response. In this study, we demonstrated that following
      mucosal delivery of herpes simplex virus type 2 (HSV-2) antigen with CAP, CAP
      adjuvant enhanced protective systemic and mucosal immunity versus live virus.
      Mice were immunized intravaginally and intranasally with HSV-2 protein plus CAP
      adjuvant (HSV-2+CAP), CAP alone, phosphate-buffered saline, or HSV-2 alone. HSV
      2+CAP induced HSV-specific mucosal IgA and IgG and concurrently enhanced systemic
      IgG responses. Our results demonstrate the potency of CAP as a mucosal adjuvant.
      Furthermore, we show that systemic immunity could be induced via the mucosal
      route following inoculation with CAP-based vaccine. Moreover, neutralizing
      antibodies were found in the sera of mice immunized intranasally or
      intravaginally with HSV-2+CAP. Also, the results of our in vivo experiments
      indicated that mice vaccinated with HSV-2+CAP were protected against live HSV-2
      infection. In conclusion, these preclinical data support the hypothesis that CAP
      may be an effective mucosal adjuvant that protects against viral infection.

PMID- 12204954
TI  - Serodiagnosis of mice minute virus and mouse parvovirus infections in mice by
      enzyme-linked immunosorbent assay with baculovirus-expressed recombinant VP2
      proteins.
AB  - Mice minute virus (MMV) and mouse parvovirus (MPV) type 1 are the two
      parvoviruses known to naturally infect laboratory mice and are among the most
      prevalent infectious agents found in contemporary laboratory mouse colonies.
      Serologic assays are commonly used to diagnose MMV and MPV infections in
      laboratory mice; however, highly accurate, high-throughput serologic assays for
      the detection of MMV- and MPV-infected mice are needed. To this end, the major
      capsid viral protein (VP2) genes of MMV and MPV were cloned and MMV recombinant
      VP2 (rVP2) and MPV rVP2 proteins were expressed by using a baculovirus system.
      MMV rVP2 and MPV rVP2 spontaneously formed virus-like particles that were
      morphologically similar to empty parvovirus capsids. These proteins were used as
      antigens in enzyme-linked immunosorbent assays (ELISAs) to detect anti-MMV or
      anti-MPV antibodies in the sera of infected mice. Sera from mice experimentally
      infected with MMV (n = 43) or MPV (n = 35) and sera from uninfected mice (n = 30)
      were used to evaluate the ELISAs. The MMV ELISA was 100% sensitive and 100%
      specific in detecting MMV-infected mice, and the MPV ELISA was 100% sensitive and
      98.6% specific in detecting MPV-infected mice. Both assays outperformed a
      parvovirus ELISA that uses a recombinant nonstructural protein (NS1) of MMV as
      antigen. The MMV rVP2 and MPV rVP2 proteins provide a ready source of easily
      produced antigen, and the ELISAs developed provide highly accurate, high
      throughput assays for the serodiagnosis of MMV and MPV infections in laboratory
      mice.

PMID- 12204955
TI  - Specificities and opsonophagocytic activities of antibodies to pneumococcal
      capsular polysaccharides in sera of unimmunized young children.
AB  - An enzyme immunoassay (EIA) for antibodies to pneumococcal capsular
      polysaccharides (Pnc PSs) detects in some cases antibodies that are cross
      reactive within different Pnc PSs. Recently, it has been suggested that for
      detection of only serotype-specific antibodies, EIA can be modified by removing
      cross-reactive antibodies by absorption with an irrelevant PS, e.g., the type 22F
      PS. The opsonophagocytosis assay measures the functional activities of antibodies
      in vitro, and the results of that assay correlate with in vivo protection better
      than measurement of the antibody concentration by EIA. We compared these
      different methods for measuring antibodies to type 1, 6B, 11A, 14, 19F, and 23F
      Pnc PSs in the sera of unimmunized young children who had been monitored for
      pneumococcal carriage, acute otitis media, and acquisition of antibodies to Pnc
      PSs from 2 to 24 months of age. Serum samples with antibody increases after
      contact with a pneumococcus of a homologous serotype contained specific
      antibodies and often had opsonophagocytic activity (OPA) (20 of 46). In samples
      with antibody increases from children who had not had contact with a pneumococcus
      of a homologous serotype, the antibodies found to be type specific by
      conventional EIA were usually cross-reactive and infrequently had OPA (10 of 68).
      When type 22F PS absorption was used in the EIA, most of the false antibody
      increases were eliminated, but most of the true antibody increases were still
      detected and the association between the antibody concentration detected by EIA
      and OPA was improved. However, there were serotype-dependent differences in the
      frequency of OPA. Use of absorption with a heterologous PS in EIA should be
      encouraged, and both the specificity of EIA and the sensitivity of
      opsonophagocytic assays should be further evaluated and improved.

PMID- 12204956
TI  - In vitro whole-blood analysis of cellular immunity in patients with active
      coccidioidomycosis by using the antigen preparation T27K.
AB  - Measurement of cellular immunity in human coccidioidomycosis has important
      diagnostic and prognostic implications. The coccidioidin skin test has been the
      standard for the measurement of this, but it is not available in the United
      States. We examined the utility of measuring surface expression of CD69 on T
      lymphocytes in whole blood incubated with the coccidioidal antigen preparation
      T27K as an alternative to the skin test. Seventy donors with active
      coccidioidomycosis were studied. The mean fluorescent intensity (MFI) of CD69
      expression on CD3 lymphocytes in response to T27K was 28.61 +/- 1.77,
      significantly greater than the control response of 11.45 +/- 0.78 (P < 0.001).
      The MFI CD69 response to T27K above that for the control (MFI CD69 above control)
      was 6.35 +/- 2.18 for seven subjects with disseminated coccidioidomycosis who
      were studied within 5 months of diagnosis. This was significantly below the value
      of 20.17 +/- 3.17 for 18 subjects with pulmonary coccidioidomycosis studied
      within 5 months of diagnosis and the value of 19.58 +/- 2.91 for 27 subjects with
      disseminated coccidioidomycosis studied after 5 months of diagnosis (for both, P
      < 0.05). There was an inverse correlation between coccidioidal clinical score and
      MFI CD69 above control for all 34 subjects with disseminated coccidioidomycosis
      (r = 0.362; P = 0.036) but not for the 36 subjects with pulmonary disease (r <
      0.001; P = 0.993). Among 30 subjects for whom data were available, there was a
      highly significant association between the MFI CD69 above control and the
      supernatant concentrations of gamma interferon, interleukin-2 (IL-2), and tumor
      necrosis factor alpha (for all, P < 0.001), but not for IL-4, IL-5, or IL-10.
      These data indicate that in vitro assessment of CD69 expression on T lymphocytes
      by using T27K may be a useful measure of cellular immune response among subjects
      with active coccidioidomycosis.

PMID- 12204957
TI  - Immunoglobulin G antibody against Helicobacter pylori: clinical implications of
      levels found in serum.
AB  - The clinical significance of high levels of antibody against Helicobacter pylori
      is still unclear. We sought to evaluate whether the serum antibody levels could
      predict the presence of macroscopic gastroduodenal disease, to identify factors
      that correlate with antibody levels in a multivariate context, and to determine
      the predictive value of antibody levels for diagnosing H. pylori infection. The
      grades of gastritis and density of H. pylori colonization were scored separately
      using the updated Sydney system for antral and body mucosa. An enzyme-linked
      immunosorbent assay (ELISA) for the quantitative detection in serum of IgG
      antibodies to H. pylori was performed. Of the 170 dyspeptic patients, 105 (62%)
      had H. pylori infection. There was no difference in antibody levels among
      endoscopic findings of normal mucosa, chronic gastritis, and duodenal ulcer. On
      multivariate linear regression analysis, the status of H. pylori infection,
      mononuclear cell infiltration of body mucosa, and age correlated with antibody
      levels. The negative predictive value for antibody levels of <30 U/ml is 94%, and
      the positive predictive value of antibody levels of >70 U/ml is 98%. We conclude
      that serum antibody levels do not predict the severity of gastroduodenal diseases
      or the density of H. pylori colonization in H. pylori-infected dyspeptic
      patients. Higher levels are associated with the presence of H. pylori infection,
      the chronic gastritis score of the corpus, and older age. Setting a gray zone is
      necessary for ELISA, since the accuracy in this zone does not allow a precise
      determination of H. pylori status.

PMID- 12204958
TI  - Spontaneous cytokine production and its effect on induced production.
AB  - Cytokines regulate cellular immune activity and are produced by a variety of
      cells, especially lymphocytes, monocytes, and macrophages. Multiparameter flow
      cytometry is often used to examine cell-specific cytokine production after in
      vitro phorbol 12-myristate 13-acetate and ionomycin induction, with brefeldin A
      or other agents added to inhibit protein secretion. Spontaneous ex vivo
      production reportedly rarely occurs. We examined the spontaneous production of
      interleukin 2 (IL-2), IL-4, IL-6, IL-8, IL-10, tumor necrosis factor alpha (TNF
      alpha), and gamma interferon (IFN-gamma) by peripheral-blood B lymphocytes, T
      cells, CD8(-) T cells, CD8(+) T cells, CD3(-) CD16/56(+) lymphocytes (natural
      killer [NK] cells), CD3(+) CD16/56(+) lymphocytes (natural T [NT] cells), and/or
      monocytes of 316 acutely ill hospitalized persons and 62 healthy adults in
      Malawi, Africa. We also evaluated the relationship between spontaneous and
      induced cytokine production. In patients, spontaneous TNF-alpha production
      occurred most frequently, followed in descending order by IFN-gamma, IL-8, IL-4,
      IL-10, IL-6, and IL-2. Various cells of 60 patients spontaneously produced TNF
      alpha; for 12 of these patients, TNF-alpha was the only cytokine produced
      spontaneously. Spontaneous cytokine production was most frequent in the
      immunoregulatory cells, NK and NT. For IL-2, IL-4, IL-6, IL-8, and IL-10,
      spontaneous cytokine production was associated with greater induced production.
      For TNF-alpha and IFN-gamma, the relationships varied by cell type. For healthy
      adults, IL-6 was the cytokine most often produced spontaneously. Spontaneous
      cytokine production was not unusual in these acutely ill and healthy persons
      living in an area where human immunodeficiency virus, mycobacterial, malaria, and
      assorted parasitic infections are endemic. In such populations, spontaneous, as
      well as induced, cell-specific cytokine production should be measured and
      evaluated in relation to various disease states.

PMID- 12204959
TI  - Bacillus species are present in chewing tobacco sold in the United States and
      evoke plasma exudation from the oral mucosa.
AB  - Five Bacillus species, predominantly Bacillus megaterium and Bacillus pumilus,
      were isolated from two popular brands of commercially available chewing tobacco
      [(5.0 +/- 1) x 10(6) CFU/ml of supernatant; results for four experiments].
      Moreover, the supernatant of the Bacillus culture evoked plasma exudation from
      postcapillary venules in the intact hamster cheek pouch, exudation that was
      mediated by the kallikrein/kinin metabolic pathway. Taken together, these data
      indicate that Bacillus species contaminate chewing tobacco commercially available
      in the United States and elaborate a potent exogenous virulence factor(s) that
      injures the oral mucosa.

PMID- 12204960
TI  - Use of egg yolk-derived immunoglobulin as an alternative to antibiotic treatment
      for control of Helicobacter pylori infection.
AB  - The present study evaluated the potential use of immunoglobulin prepared from the
      egg yolk of hens immunized with Helicobacter pylori (immunoglobulin Y [IgY]-Hp)
      in the treatment of H. pylori infections. The purity of our purified IgY-Hp was
      91.3%, with a yield of 9.4 mg of IgY per ml of egg yolk. The titer for IgY-Hp was
      16 times higher than that for IgY in egg yolk from nonimmunized hens, and IgY-Hp
      significantly inhibited the growth and urease activity of H. pylori in vitro.
      Bacterial adhesion on AGS cells was definitely reduced by preincubation of both
      H. pylori (10(8) CFU/ml) and 10 mg of IgY-Hp/ml. In Mongolian gerbil models, IgY
      Hp decreased H. pylori-induced gastric mucosal injury as determined by the degree
      of lymphocyte and neutrophil infiltration. Therefore, in this experimental model,
      H. pylori-associated gastritis could be successfully treated by orally
      administered IgY-Hp. The immunological activity of IgY-Hp stayed active at 60
      degrees C for 10 min, suggesting that pasteurization can be applied to sterilize
      the product. Fortification of food products with this immunoglobulin would
      significantly decrease the H. pylori infection. In conclusion, the IgY-Hp
      obtained from hens immunized by H. pylori could provide a novel alternative
      approach to treatment of H. pylori infection.

PMID- 12204961
TI  - Immunoglobulin G antibody response to infection with coccoid forms of
      Helicobacter pylori.
AB  - An increasing number of studies support a potential role for coccoid forms in
      Helicobacter pylori infection. Evidence for this was obtained through scanning
      microscopy, genetic analysis for virulence traits, examination of the presence
      and activity of key enzymes, and other methods. We studied the serum
      immunoglobulin G responses to coccoid H. pylori forms by enzyme-linked
      immunosorbent assay (ELISA) and immunoblotting and compared them with those of
      bacillary cells. Sera from a total of 295 infected individuals were studied;
      these included sera from 100 patients with duodenal ulcers, 98 patients with
      nonulcer dyspepsia, 11 patients with gastroduodenal cancer, and 86 asymptomatic
      individuals. Initially, we characterized and selected coccoid and bacillary
      antigenic preparations by one-dimensional (1-D) and 2-D gel electrophoresis and
      immunoblotting. Data showed that coccoid and bacillary preparations with
      comparable protein contents have similar patterns in 1-D and 2-D electrophoresis
      gels and antigenic recognition at blotting. These results revealed that coccoid
      and spiral antigens in ELISA can equally recognize specific antibodies to H.
      pylori in sera from infected individuals. The analysis of the spiral and coccoid
      preparations by Western blotting showed no major differences in antigen
      recognition. No specific bands or profiles associated with a single gastric
      condition were identified.

PMID- 12204962
TI  - Clinical and epidemiological relevance of quantitating hepatitis E virus-specific
      immunoglobulin M.
AB  - Diagnosis of acute hepatitis E by detection of hepatitis E virus (HEV)-specific
      immunoglobulin M (IgM) is an established procedure. We investigated whether
      quantitation of HEV IgM and its ratio to HEV total Ig furnished more information
      than conventional IgM tests that are interpreted as positive or negative. A
      previously described indirect immunoassay for total Ig against a baculovirus
      expressed HEV capsid protein was modified to quantitate HEV-specific IgM in
      Walter Reed (WR) antibody units by using a reference antiserum and the four
      parameter logistic model. A receiver-operating characteristics curve derived from
      197 true-positive specimens and 449 true-negative specimens identified 30 WR
      units/ml as an optimum cut point. The median HEV IgM level in 36 patients with
      acute hepatitis E fell from 3,000 to 100 WR units/ml over 6 months, suggesting
      that 100 WR units/ml would be a more appropriate cut point for distinguishing
      recent from remote IgM responses. Among three hepatitis E case series,
      determination of the HEV IgM-to-total-Ig ratio in acute-phase serum revealed that
      most patients had high ratios consistent with primary infections whereas a few
      had low ratios, suggesting that they had sustained reinfections that elicited
      anamnestic antibody responses. The diagnostic utility of the new IgM test was
      similar to that of a commercially available test that uses different HEV
      antigens. In conclusion, we found that HEV IgM can be detected specifically in
      >95% of acute hepatitis E cases defined by detection of the virus genome in serum
      and that quantitation of HEV IgM and its ratio to total Ig provides insight into
      infection timing and prior immunity.

PMID- 12204963
TI  - Cytokine gene expression by peripheral blood leukocytes in horses experimentally
      infected with Anaplasma phagocytophila.
AB  - Human granulocytic ehrlichiosis (HGE), a tick-borne zoonosis, is caused by an
      obligatory intragranulocytic bacterium, the HGE agent, a strain of Anaplasma
      phagocytophila. The equine model of HGE is considered valuable in understanding
      pathogenic and immune mechanisms of HGE. In the present study, cytokine mRNA
      expression by peripheral blood leukocytes (PBLs) in horses was examined during
      the course of infection by intravenous inoculation of A. phagocytophila or by
      allowing feeding by infected ticks. The p44 genes encoding the major outer
      membrane protein P44s of A. phagocytophila were detected by PCR in PBLs of all
      four horses from 4 to 20 days postexposure. During the 20-day infection period,
      interleukin-1beta (IL-1beta) and tumor necrosis factor alpha (TNF-alpha) mRNA
      expression was upregulated in PBLs of all four horses, and IL-8 mRNA expression
      was upregulated in three horses. Gamma interferon, IL-10, and IL-12 p35 mRNAs
      were weakly expressed in only one horse each. IL-2, IL-4, IL-6, and IL-12 p40
      mRNA expression, however, could not be detected in the PBLs of any of the four
      horses. These results suggest that IL-1beta, TNF-alpha, and IL-8 generation
      during A. phagocytophila infection has a primary role in HGE pathogenesis and
      immunomodulation.

PMID- 12204964
TI  - Affordable CD4(+)-T-cell counting by flow cytometry: CD45 gating for volumetric
      analysis.
AB  - The flow cytometers that are currently supported by industry provide accurate
      CD4(+)-T-cell counts for monitoring human immunodeficiency virus disease but
      remain unaffordable for routine service work under resource-poor conditions. We
      therefore combined volumetric flow cytometry (measuring absolute lymphocyte
      counts in unit volumes of blood) and simpler protocols with generic monoclonal
      antibodies (MAbs) to increase cost efficiency. Volumetric absolute counts were
      generated using CD45/CD4 and CD45/CD8 MAb combinations in two parallel tubes. The
      percentage values for the various subsets were also determined within the
      leukocyte and lymphocyte populations utilizing a fully automated protocol. The
      levels of agreement between the newly developed method and the present industry
      standards, including both volumetric and bead-based systems using a full MAb
      panel for subset analysis, were tested by Bland-Altman analyses. The limits of
      agreement for CD4 counts generated by the volumetric methods using either
      CD45/CD4 (in a single tube) or the full Trio MAb panel (in three tubes) on the
      CytoronAbsolute flow cytometer were between -29 and +46 cells/mm(3) with very
      little bias for CD4 counts (in favor of the Trio method: +8 CD4(+)
      lymphocytes/mm(3); 0.38% of lymphocytes). The limits of agreement for absolute
      CD4 counts yielded by the volumetric CD45/CD4 method and the bead-based method
      were between -118 and +98 cells/mm(3), again with a negligible bias (-10 CD4(+)
      lymphocytes/mm(3)). In the volumetric method using CD45/CD8, the strongly CD8(+)
      cells were gated and the levels of agreement with the full Trio showed a minor
      bias (in favor of the Trio; +40 CD8(+) cells/mm(3); 5.2% of lymphocytes) without
      a significant influence on CD4/CD8 ratios. One trained flow cytometrist was able
      to process 300 to 400 stained tubes per day. This workload extrapolates to a
      throughput of >30,000 samples per year if both CD45/CD4 and CD45/CD8 stainings
      are performed for each patient or a throughput of >60,000 samples if only
      CD45/CD4 counts are tested in a single tube. Thus, on the basis of the high
      efficiency and excellent agreement with the present industry standards,
      volumetric flow cytometers with automated gating protocols and autobiosamplers,
      complemented by generic CD45, CD4, and CD8 MAbs used in two-color
      immunofluorescence, represent the most suitable arrangements for large regional
      laboratories in resource-poor settings.

PMID- 12204965
TI  - Gamma interferon inhibits production of Anti-OspA borreliacidal antibody in
      vitro.
AB  - The ability of a Lyme borreliosis vaccine to induce and maintain sustained levels
      of borreliacidal antibody is necessary for prolonged protection against infection
      with Borrelia burgdorferi. Vaccination against infection with B. burgdorferi
      could be improved by determining the mechanism(s) that influences the production
      of protective borreliacidal antibody. Borreliacidal antibody was inhibited in
      cultures of lymph node cells obtained from C3H/HeJ mice vaccinated with formalin
      inactivated B. burgdorferi and cultured with macrophages and B. burgdorferi and
      treated with recombinant gamma interferon (rIFN-gamma). The suppression of
      production of outer surface protein A (OspA) borreliacidal antibody by rIFN-gamma
      was not affected by the time of treatment. In addition, treatment with rIFN-gamma
      inhibited the production of other anti-B. burgdorferi antibodies. By contrast,
      treatment of cultures of immune lymph node cells with anti-IFN-gamma marginally
      increased the production of borreliacidal antibody and enhanced the production of
      other antibodies directed against B. burgdorferi. These results show that IFN
      gamma does not play a major role in the production of anti-OspA borreliacidal
      antibody. Additional studies are needed to determine which cytokine(s) will
      enhance production of borreliacidal antibody.

PMID- 12204966
TI  - Suppression of growth by all-trans retinoic acid requires prolonged induction of
      interferon regulatory factor 1 in cervical squamous carcinoma (SiHa) cells.
AB  - All-trans retinoic acid (ATRA) suppresses growth of cervical dysplasias in vivo,
      although the sensitivity to retinoids is frequently lost during cervical
      carcinogenesis. It has been suggested that prolonged treatment or use of higher
      doses of retinoids might offer favorable response rates. We found SiHa cervical
      squamous carcinoma cells that were virtually resistant to ATRA-induced growth
      inhibitory effects at physiological doses (10(-7 to) 10(-6) M) to be more
      responsive at pharmacological doses (10(-5 to) 10(-4) M). The growth inhibition
      by high-dose (10(-4) M) ATRA was associated with a sustained activation of
      interferon regulatory factor 1 (IRF-1), while a low dose (10(-6) M) of ATRA
      activated IRF-1 only transiently. Antisense IRF-1 inhibited the high-dose (10(-4)
      M), ATRA-mediated growth arrest; forced expression of IRF-1 caused a significant
      reduction in cell growth. High-dose (10(-4) M) ATRA increased binding of NF
      kappaB and STAT1 proteins to sequences that originated from the IRF-1 promoter
      region, while low-dose (10(-6) M) ATRA induced only NF-kappaB binding. A delayed
      tyrosine phosphorylation of the signal transducer and activator of transcription
      1 (STAT1) was observed after high-dose (10(-4) M) but not low-dose (10(-6) M)
      ATRA treatment. In agreement with this, induction of IRF-1 mRNA by ATRA was only
      modest and transient in a STAT1 knockout cell line, suggesting the importance of
      STAT1 in sustained IRF-1 expression. Our data showed that ATRA is capable of
      inducing dose-dependent cellular changes, which might be appropriate to overcome
      resistance to retinoids that frequently develops during cervical carcinogenesis.

PMID- 12204967
TI  - Double-blind study to evaluate flow cytometry analysis of anti-live
      trypomastigote antibodies for monitoring treatment efficacy in cases of human
      Chagas' disease.
AB  - The validation of flow cytometry analysis of anti-live trypomastigote antibodies
      (FC-ALTA) to monitor cure after treatment of Chagas' disease was evaluated with
      serum samples from treated and nontreated chagasic patients. After optimization
      of the original technique, toward better sensitivity and applicability to field
      surveys, we design a double blind study of 94 coded samples classified into the
      following categories: patients not treated (NT) and patients treated but not
      cured (TNC), both presenting positive conventional serology and xenodiagnosis;
      patients treated and cured (TC), showing negative serology and xenodiagnosis; and
      patients treated under evaluation (TUE), who presented positive or oscillating
      conventional serology (CSA) but negative xenodiagnosis. Coded samples, diluted
      1:256, were assayed by incubation with live cell culture trypomastigotes, which
      were subsequently stained with fluorescein isothiocyanate-conjugated anti-human
      immunoglobulin G, with prior fixation and analysis by flow cytometry. The results
      were expressed as the percentages of positive fluorescent parasites (PPFP) for
      each individual sample, establishing 20% PPFP as the cutoff between negative and
      positive results. Our data demonstrated that all NT and TNC presented positive
      results while all but one TC had a PPFP lower than 20%. Analysis of TUE
      demonstrated a wide degree of reactivity, with PPFP values that were negative
      (PPFP </= 20%), low positive (20% < PPFP </= 50%), and high positive (PPFP >
      50%). As TUE with negative PPFP presented negative xenodiagnosis and positive or
      oscillating CSA, they were classified as dissociated according to the criteria of
      Krettli and Brener (J. Immunol. 128:2009-2012, 1982) and could indeed be
      considered cured after chemotherapy. This study demonstrates and validates the
      use of FC-ALTA to easily identify anti-live trypomastigote membrane-bound
      antibodies, offering another approach for investigating and monitoring the
      efficacy of specific chemotherapy in cases of human Chagas' disease.

PMID- 12204968
TI  - Modulation of human immunodeficiency virus (HIV)-specific immune response by
      using efavirenz, nelfinavir, and stavudine in a rescue therapy regimen for HIV
      infected, drug-experienced patients.
AB  - Analysis of the virologic and immunomodulatory effects of an association of
      efavirenz (EFV), nelfinavir (NFV), and stavudine (d4T) was performed in 18 human
      immunodeficiency virus (HIV)-infected and highly active antiretroviral therapy
      (HAART)-experienced patients who failed multiple therapeutic protocols. Patients
      (<500 CD4(+) cells/ micro l; >10,000 HIV copies/ml) were nonnucleoside reverse
      transcriptase inhibitor (NNRTI)-naive and were treated for 10 months with EFV
      (600 mg/day) in association with NFV (750 mg three times daily) and d4T (30 or 40
      mg twice daily). Measurement of HIV peptide- and mitogen-stimulated production of
      interleukin-2 (IL-2), gamma interferon (IFN-gamma), IL-4, and IL-10 as well as
      quantitation of mRNA for the same cytokines in unstimulated peripheral blood
      mononuclear cells were performed at baseline and 2 weeks (t1), 2 months (t2), and
      10 months (t3) into therapy. The results showed that HIV-specific (but not
      mitogen-stimulated) IL-2 and IFN-gamma production was augmented and IL-10
      production was reduced in patients who received EFV, NFV, and d4T. Therapy was
      also associated with a reduction in HIV RNA in plasma and an increase in CD4(+)
      cell count. These changes occurred in the first year of therapy (t2 and t3) and
      were confirmed by quantitation of cytokine-specific mRNA. Therapy with EFV, NFV,
      and d4T increases HIV-specific type 1 cytokine production as well as CD4 counts
      and reduces plasma viremia. This therapeutic regimen may be considered for use in
      cases of advanced HIV infection.

PMID- 12204969
TI  - Immunoblot analysis of the humoral immune response to Leishmania donovani
      polypeptides in cases of human visceral leishmaniasis: its usefulness in
      prognosis.
AB  - Sera from Indian patients with parasitologically confirmed visceral leishmaniasis
      were studied by immunoblot analysis in order to identify a specific pattern for
      Leishmania infection. A soluble extract of Leishmania donovani was used as
      antigen. At diagnosis the sera from patients with visceral leishmaniasis
      specifically recognized fractions represented by bands of 201 kDa (50% of serum
      samples), 193 kDa (60%), 147 kDa (50%), 120 kDa (60%), 100 kDa (50%), 80 kDa
      (80%), 70 kDa (70%), 65 kDa (100%), 50 kDa (50%), 36 kDa (50%), 20 kDa (70%), and
      18 kDa (50%). The 65-kDa band, common to all patients infected with Leishmania
      parasites, was found at the time of diagnosis. However, the immunoblot pattern
      changed after patients were treated and cured with sodium antimony gluconate
      (SAG; n =10) or miltefosine (n =10), as was evident from blots of sera obtained
      pretreatment and at 1, 3, and 6 months posttreatment. At 6 months posttreatment,
      immunoblots of sera from patients on the SAG regimen showed the disappearance of
      all bands except the 70-kDa band. Similarly, sera from those on the miltefosine
      regimen showed the disappearance of all bands except the 65- and 70-kDa bands.
      This study shows that Western blot analysis is a sensitive test for detection of
      anti-Leishmania antibodies. Moreover, the persistence of reactivity with the 65-
      and 70-kDa bands in the sera of all groups shows its promise as a diagnostic and
      prognostic tool.

PMID- 12204970
TI  - Performance of two commercial glycoprotein G-based enzyme immunoassays for
      detecting antibodies to herpes simplex viruses 1 and 2 in children and young
      adolescents.
AB  - In 61 patients 1 to 14 years of age, the Gull/Meridian enzyme-linked
      immunosorbent assay (ELISA) had a sensitivity of 100% for herpes simplex virus
      type 1 (HSV-1) and specificities of 74% for HSV-1 and 48% for HSV-2. In 128
      similarly aged patients, the HerpeSelect ELISA (Focus Technologies) showed
      sensitivities of 80% for HSV-1 and 88% for HSV-2, and specificities of 97% for
      HSV-1 and 100% for HSV-2.

PMID- 12204971
TI  - Helicobacter pylori-specific immune responses of children: implications for
      future vaccination strategy.
AB  - We analyzed the specific anti-Helicobacter pylori immunoglobulin G (IgG) antibody
      profile for a sample of 824 asymptomatic schoolchildren in southern Germany (mean
      age, 10.7 +/- 0.65 years) with an H. pylori-specific IgG enzyme-linked
      immunosorbent assay and Western blot analysis. The prevalence of infection was
      19.8% (95% confidence interval, 17.1 to 22.7%). The immunoresponses were
      characterized predominantly by antibodies against low-molecular-mass antigens of
      14 and 29 kDa, with a significant difference between children of German and
      Turkish nationalities (P = 0.0012 and P < 0.0001, respectively).

PMID- 12204972
TI  - CD4(+) CD25(+) T-cell production in healthy humans and in patients with thymic
      hypoplasia.
AB  - Regulatory T cells are found primarily in the CD4(+) CD25(+) fraction of T cells
      and play an important role in the prevention of autoimmunity. We examined CD4(+)
      CD25(+) T cells in 33 healthy children and adults and compared them to a
      population with an inherited form of thymic hypoplasia and a predisposition to
      autoimmune disease. Absolute numbers of CD4(+) CD25(+) T cells were markedly
      higher in healthy infants than in infants with chromosome 22q11.2 deletion
      syndrome.

PMID- 12204973
TI  - Determination of the nucleotide sequences of heat shock operon groESL and the
      citrate synthase gene (gltA) of Anaplasma (Ehrlichia) platys for phylogenetic and
      diagnostic studies.
AB  - The 1,670-bp nucleotide sequence of the heat shock operon groESL and the 1,236-bp
      sequence of the citrate synthase gene (gltA) of Anaplasma (Ehrlichia) platys were
      determined. The topology of the groEL- and gltA-based phylogenetic tree was
      similar to that derived from 16S rRNA gene analyses with distances. Both groESL-
      and gltA-based PCRs specific to A. platys were also developed based upon the
      alignment data.

PMID- 12204975
TI  - Centrifugation of human lung epithelial carcinoma a549 cells up-regulates
      interleukin-1beta gene expression.

PMID- 12204974
TI  - Diagnostic techniques to detect cryptic leishmaniasis in dogs.
AB  - This study of several techniques for detecting cryptic leishmaniasis in dogs from
      areas in Spain where Leishmania infantum is highly endemic concludes that
      immunological techniques (enzyme-linked immunosorbent assay, immunofluorescence
      antibody test, Western blotting, delayed-type hypersensitivity reaction, and in
      vitro lymphocyte proliferation assay) do not clearly differentiate between
      noninfected and infected asymptomatic dogs and that culture and PCR are more
      reliable diagnostic tools.

PMID- 12204977
TI  - Emergency medicine in differently resourced settings: what can we offer each
      other?

PMID- 12204978
TI  - Information exchange is two way.

PMID- 12204979
TI  - Challenges and changes.

PMID- 12204980
TI  - Use of tissue adhesives in the management of paediatric lacerations.

PMID- 12204981
TI  - Chronic and occult carbon monoxide poisoning: we don't know what we're missing.

PMID- 12204982
TI  - Registry based trauma outcome: perspective of a developing country.
AB  - OBJECTIVE: To report trauma outcome from a developing country based on the Trauma
      and Injury Severity Scoring (TRISS) method and compare the outcome with the
      registry data from Major Trauma Outcome Study (MTOS). DESIGN: Registry based
      audit of all trauma patients over two years. SETTING: Emergency room of a
      teaching university hospital. SUBJECTS: 279 injured patients meeting trauma team
      activation criteria including all deaths in the emergency room. OUTCOME MEASURES:
      TRISS methodology to compare expected and observed outcome. STATISTICAL ANALYSIS:
      W, M, and Z statistics and comparison with MTOS data. RESULTS: 279 patients
      meeting the trauma triage criteria presented to the emergency room, 235 (84.2%)
      were men and 44 (15.8%) women. Blunt injury accounted for 204 (73.1%) and
      penetrating for 75 (26.9%) patients. Seventy two patients had injury severity
      score of more than 15. Only 18 (6.4%) patients were transported in an ambulance.
      A total of 142 (50.9%) patients were transferred from other hospitals with a mean
      prehospital delay of 7.1 hours. M statistic of our study subset was 0.97,
      indicating a good match between our patients and MTOS cohort. There were 18
      deaths with only one unexpected survivor. The expected number of deaths based on
      MTOS dataset should have been 12. CONCLUSIONS: Present injury severity
      instruments using MTOS coefficients do not accurately correlate with observed
      survival rates in a developing country.

PMID- 12204983
TI  - ROMEO: a rapid rule out strategy for low risk chest pain. Does it work in a UK
      emergency department?
AB  - AIMS: To examine the feasibility of using the ROMEO (rule out myocardial events
      on "obs" ward) pathway for low risk patients with chest pain in a UK emergency
      department. METHODS: A prospective study was undertaken to determine outcomes for
      the first 100 patients entering the pathway (from May to Oct 1999). Serum
      troponin levels, serial ECG recordings, exercise test result, total length of
      stay, and final diagnoses were reviewed. Patients were telephoned after discharge
      to inquire about persisting or recurrent pain, and further investigations after
      completing the ROMEO pathway. RESULTS: 82 of 100 (82%) had myocardial damage
      excluded by serum troponin assay. Sixty two of 82 (76%) of these completed
      exercise tolerance testing (ETT). Fifty seven of 62 (92%) ETTs were negative.
      Twenty of 82 (26%) did not undergo ETT because of mobility problems, recent ETT,
      or if considered very low probability of cardiac pain on consultant review. Five
      of 100 (5%) had an increased initial troponin and five of 100 (5%) had an
      increased 12 hour troponin. These patients were referred for admission under the
      general physicians. Seven of 100 (7%) were referred for other reasons (late ECG
      changes, continuing or worsening pain). One patient self discharged. Length of
      stay varied because of changes to arrangements for ETT. The median time for all
      patients over the period studied was 23 hours. All patients were discharged
      within an hour of a negative ETT. FOLLOW UP RESULTS: 67 of 74 (91%) eligible
      patients were contacted by telephone. Forty six of 67 (69%) had no further pain,
      attendances, or GP consultations. Six of 67 (9%) had further cardiological
      investigation or treatment. CONCLUSIONS: A rapid rule out strategy such as the
      ROMEO pathway is feasible in the UK healthcare setting and provides standardised
      and consistent evaluation.

PMID- 12204984
TI  - The psychological burden of injury: an 18 month prospective cohort study.
AB  - OBJECTIVES: To determine the prevalence of post-trauma psychological problems
      among a cohort of male accident and emergency department patients admitted to
      hospital. To identify the changes in their psychological symptoms over an 18
      month follow up period. METHODS: A prospective cohort study of male accident and
      emergency department patients who were admitted for treatment of an injury.
      Baseline interview recorded demographic details and accident details.
      Standardised questionnaires measured baseline psychological state and personality
      type. Follow up at six weeks, six months, and 18 months after injury was by face
      to face interview or postal questionnaire and recorded progress since injury, and
      documented psychological status through the use of standardised questionnaires to
      detect psychiatric disorder and symptoms of post-traumatic stress disorder
      (PTSD). RESULTS: 210 male patients were recruited into the study. Psychiatric
      disorder was identified in 47.6% of responders at six weeks, and 43.4% at six
      months after injury. This improved significantly at 18 months. PTSD symptoms were
      moderate in 25%-30% and severe in 5%-14% and did not change significantly over
      the study period. A significant relation was found between previous psychiatric
      history and psychological symptoms at 18 months after injury. No relation was
      identified between injury severity and psychological status after injury.
      CONCLUSION: This study finds a high prevalence of psychological distress in male
      accident and emergency department patients after injury. Although some symptoms
      resolve over the follow up period, a proportion remain and may be related to
      previous psychiatric history. There was no relation identified between severity
      of injury and psychological morbidity.

PMID- 12204985
TI  - A randomised, controlled trial comparing a tissue adhesive (2-octylcyanoacrylate)
      with adhesive strips (Steristrips) for paediatric laceration repair.
AB  - OBJECTIVE: To compare the tissue adhesive 2-octylcyanoacrylate (Dermabond) with
      adhesive strips, Steristrips in paediatric laceration repair. METHOD: Children
      with suitable lacerations were randomly allocated for wound closure with either a
      tissue adhesive or adhesive strips. Thirty children were treated in each group.
      Linear Visual Analogue Scores were used to judge parents' and nurses' opinions of
      the application of each treatment. A similar scoring system was used to judge the
      cosmetic outcome as viewed by parents and a plastic surgeon. Complications and
      trial failures were noted. RESULTS: Complete data were available for 44 of the
      children. Parents viewed the treatments as equally acceptable. In contrast those
      performing the procedure judged the tissue adhesive more difficult to apply.
      Scores of cosmetic outcome by both parents and the plastic surgeon showed no
      significant difference in the treatment method used. There were four children in
      the tissue adhesive group and one from the adhesive strip group in whom the
      wounds were unable to be closed. CONCLUSION: Both tissue adhesives and adhesive
      strips are excellent "no needle" alternatives for the closure of suitable
      paediatric lacerations. This study suggests that the techniques are similar in
      efficacy, parental acceptability, and cosmetic outcome. The choice as to which is
      used may come down to economics and operator preference.

PMID- 12204986
TI  - Measuring plasma paracetamol concentrations in all patients with drug overdoses;
      development of a clinical decision rule and clinicians willingness to use it.
AB  - OBJECTIVES: The study proposed a clinical decision rule: In patients who have
      taken a deliberate overdose, but deny taking paracetamol or paracetamol
      containing compounds, who have a GCS of 15, understand English well, and have not
      taken excessive alcohol, there is no need to take blood for paracetamol
      estimation. METHODS: 307 consecutive emergency department patients were followed
      up, and the history of their overdose was correlated to blood paracetamol
      concentrations. In addition, clinicians were asked what level of confidence they
      required from such a clinical decision rule before they would use it. RESULTS:
      152 admitted paracetamol and 155 denied it. Of the 155 that denied it, 13 had
      concentrations detected in the blood, but needed no treatment with antidote.
      Eighty three per cent of clinicians require a false negative rate of less than
      1%. CONCLUSIONS: Using this decision rule, only 46 of 307 patients would not have
      required paracetamol concentrations to be measured. To show a negative rate of
      less than 1% a sample size of 20,000 patients would be needed. BOTTOM LINE: All
      patients who allege taking an overdose need paracetamol concentrations checking.

PMID- 12204987
TI  - A changing pattern of injuries to horse riders.
AB  - OBJECTIVES: To describe the demographics and nature of injuries occurring on or
      around horses, to examine the nature of protective clothing in relation to these
      injuries, and to compare our data with previously published work in this area.
      METHODS: Patients were identified using the term "sports injury-horse riding"
      from the departmental database for one calendar year from February 2000. Data
      were collected regarding demographics, injuries, protective clothing, and
      outcome. The data were then analysed and compared with the previously published
      literature. RESULTS: 260 patients' records were analysed. The patients were
      mostly young (median age 26) and female (84.6%). The majority of patients had a
      single injury (88.8%). Seventeen per cent had an isolated head injury, all of
      which proved to be minor. Multiple injuries including the head accounted for 8.5%
      of all injuries. These again proved minor, bar one fatality where the helmet came
      off before impact. Upper limb injuries accounted for 29.2% of all injuries of
      which 61.8% sustained a fracture of which 36.2% were to the wrist. When compared
      with previous work the incidence and severity of head injury continues to decline
      while the relative number and severity of upper limb injuries increases.
      CONCLUSIONS: The majority of head injured riders are wearing approved helmets and
      sustaining only minor injury. There is currently no protective gear recommended
      for the upper limb and more specifically the wrist. This paper identifies the
      potential need for research and development of such protection.

PMID- 12204988
TI  - Fatal asthma or anaphylaxis?
AB  - The incidence of anaphylaxis is under-reported. Children with asthma are
      frequently atopic and prone to allergic reactions. Parents and clinicians may
      attribute wheeze of rapid onset to acute severe asthma, rather than recognising
      an anaphylactic event. Two cases of fatal anaphylaxis are reported who were
      initially diagnosed as acute severe asthma, and responded poorly to
      bronchodilator treatment. Survivors of "acute asphyxic asthma" should be screened
      for reactions to common allergens that provoke anaphylactic reactions. Even if no
      provoking factor is identified, the asthma management plan of children who
      survive an episode of acute asphyxic asthma should include intramuscular
      adrenaline (epinephrine) in addition to conventional bronchodilators.

PMID- 12204989
TI  - Is cocaine needed in topical anaesthesia?

PMID- 12204990
TI  - Ethical considerations in accident and emergency research.

PMID- 12204991
TI  - Towards evidence based emergency medicine: best BETs from the Manchester Royal
      Infirmary. Electrical stimulation and Bell's palsy.
AB  - A short cut review was carried out to establish whether electrical stimulation
      had any advantages over facial exercises in promoting recovery after Bell's
      palsy. Altogether 270 papers were found using the reported search, of which one
      presented the best evidence to answer the clinical question. The author, date,
      and country of publication, patient group studied, study type, relevant outcomes,
      results, and study weaknesses of this best paper are tabulated. A clinical bottom
      line is stated.

PMID- 12204992
TI  - Towards evidence based emergency medicine: best BETs from the Manchester Royal
      Infirmary. White cell count and diagnosing appendicitis in children.
AB  - A short cut review was carried out to establish whether a single white cell count
      has clinical utility in the diagnosis of acute appendicitis in children.
      Altogether 100 papers were found using the reported search, of which four
      presented the best evidence to answer the clinical question. The author, date,
      and country of publication, patient group studied, study type, relevant outcomes,
      results, and study weaknesses of these best papers are tabulated. A clinical
      bottom line is stated.

PMID- 12204994
TI  - Towards evidence based emergency medicine: best BETs from the Manchester Royal
      Infirmary. White cell count and diagnosing appendicitis in adults.
AB  - A short cut review was carried out to establish whether a single white cell count
      has clinical utility in the diagnosis of acute appendicitis in adults. Altogether
      176 papers were found using the reported search, of which five presented the best
      evidence to answer the clinical question. The author, date, and country of
      publication, patient group studied, study type, relevant outcomes, results, and
      study weaknesses of these best papers are tabulated. A clinical bottom line is
      stated.

PMID- 12204995
TI  - Towards evidence based emergency medicine: best BETs from the Manchester Royal
      Infirmary. Serum amylase or lipase to diagnose pancreatitis in patients
      presenting with abdominal pain.
AB  - A short cut review was carried out to establish whether serum amylase was better
      than serum lipase in the diagnosis of pancreatitis in patients presenting with
      abdominal pain. Altogether 320 papers were found using the reported search, of
      which seven presented the best evidence to answer the clinical question. The
      author, date, and country of publication, patient group studied, study type,
      relevant outcomes, results, and study weaknesses of these best papers are
      tabulated. A clinical bottom line is stated.

PMID- 12204996
TI  - Towards evidence based emergency medicine: best BETs from the Manchester Royal
      Infirmary. Management of acute ethylene glycol poisoning.
AB  - A short cut review was carried out to establish whether methylpyrazole is better
      than ethanol and/or haemodialysis in the treatment of ethylene glycol poisoning.
      Altogether 524 papers were found using the reported search, of which none
      presented any evidence to answer the clinical question. Two papers reported
      relevant case series. The author, date, and country of publication, patient group
      studied, study type, relevant outcomes, results, and study weaknesses of these
      papers are tabulated.

PMID- 12204997
TI  - Towards evidence based emergency medicine: best BETs from the Manchester Royal
      Infirmary. Bed rest after lumbar puncture.
AB  - A short cut review was carried out to establish whether a period of bed rest
      reduces the incidence of headache or other complications in patients undergoing
      diagnostic lumbar puncture. Altogether 85 papers were found using the reported
      search, of which five presented the best evidence to answer the clinical
      question. The author, date, and country of publication, patient group studied,
      study type, relevant outcomes, results, and study weaknesses of these best papers
      are tabulated. A clinical bottom line is stated.

PMID- 12204998
TI  - Towards evidence based emergency medicine: best BETs from the Manchester Royal
      Infirmary. Difficult intubation, the bougie and the stylet.
AB  - A short cut review was carried out to establish whether a gum elastic bougie is
      more effective than a stylet at improving the success rate in difficult
      intubation. Altogether 32 papers were found using the reported search, of which
      one presented the best evidence to answer the clinical question. The author,
      date, and country of publication, patient group studied, study type, relevant
      outcomes, results, and study weaknesses of this best paper are tabulated. A
      clinical bottom line is stated.

PMID- 12204999
TI  - Towards evidence based emergency medicine: best BETs from the Manchester Royal
      Infirmary. To stab or slash: the percutaneous dilatation or standard surgical
      approach to cricothyroidotomy in prehospital care.
AB  - A short cut review was carried out to establish whether surgical or percutaneous
      dilatation techniques offer better success rates in emergency cricothyroidotomy.
      Altogether 114 papers were found using the reported search, of which two
      presented the best evidence to answer the clinical question. The author, date,
      and country of publication, patient group studied, study type, relevant outcomes,
      results, and study weaknesses of these best papers are tabulated. A clinical
      bottom line is stated.

PMID- 12205000
TI  - British Thoracic Society guidelines on non-invasive ventilation.

PMID- 12205001
TI  - Article 10 media handling, consent in children, and some one wants you to spend 2
      million pounds sterling.

PMID- 12205002
TI  - The case for urban prehospital thrombolysis.
AB  - This is the first part in a debate on the benefits and disadvantages of urban
      prehospital thrombolysis. I put the case for prehospital thrombolysis in the
      urban environment and argue that it is a rational development that will save
      lives and reduce long term morbidity.

PMID- 12205003
TI  - Is prehospital thrombolysis for acute myocardial infarction warranted in the
      urban setting? The case against.
AB  - This paper forms the second part of the debate on prehospital thrombolysis (PHT).
      It is argued that large scale studies have failed to show a benefit for PHT, even
      when the time saved over conventional treatment was considerably greater than
      would be the case in the UK urban setting. In practice, a relatively small
      proportion of the total population receiving thrombolysis would receive PHT.
      Other strategies to reduce time to thrombolysis can benefit all patients and are
      likely to be more cost effective and safer.

PMID- 12205005
TI  - Emergency (999) calls to the ambulance service that do not result in the patient
      being transported to hospital: an epidemiological study.
AB  - OBJECTIVE: To describe the demographic and clinical characteristics of patients
      who are not transported to hospital after an emergency (999) call to the East
      Midlands Ambulance Service, the reason for non-transportation, and the priority
      assigned when the ambulance is dispatched. METHODS: The first 500 consecutive non
      transported patients from 1 March 2000 were identified from the ambulance service
      command and control data. Epidemiological and clinical data were then obtained
      from the patient report form completed by the attending ambulance crew and
      compared with the initial priority dispatch (AMPDS) code that determined the
      urgency of the ambulance response. RESULTS: Data were obtained for 498 patients.
      Twenty six per cent of these calls were assigned an AMPDS delta code (the most
      urgent category) at the time the call was received. Falls accounted for 34% of
      all non-transported calls. This group of patients were predominantly elderly
      people (over 70 years old) and the majority (89%) were identified as less urgent
      (coded AMPDS alpha or bravo) at telephone triage. The mean time that an ambulance
      was committed to each non-transported call was 34 minutes. CONCLUSIONS: This
      study shows that falls in elderly people account for a significant proportion of
      non-transported 999 calls and are often assigned a low priority when the call is
      first received. There could be major gains if some of these patients could be
      triaged to an alternative response, both in terms of increasing the ability of
      the ambulance service to respond faster to clinically more urgent calls and
      improving the cost effectiveness of the health service. The AMPDS priority
      dispatch system has been shown to be sensitive but this study suggests that its
      specificity may be poor, resulting in rapid responses to relatively minor
      problems. More research is required to determine whether AMPDS prioritisation can
      reliably and safely identify 999 calls where an alternative to an emergency
      ambulance would be a more appropriate response.

PMID- 12205006
TI  - Facilities for chemical decontamination in accident and emergency departments in
      the United Kingdom.
AB  - OBJECTIVE: To audit the facilities for chemical decontamination, with special
      reference to cyanide poisoning, in all major accident and emergency departments
      in the UK. METHOD: A simple postal questionnaire was used to audit planning,
      premises, equipment, protection for staff, and stocks of specific antidotes to
      cyanide poisoning. RESULTS: 227 questionnaires from 261 departments (87%) were
      returned and used in the survey. Of the 227 departments who responded, 151 (66%)
      had a written plan; 168 (74%) departments had premises for decontamination; 55
      (24%) were judged to have satisfactory premises; 146 (64%) departments had a
      shower or hose for decontamination; 60 (26%) departments had a decontamination
      trolley suitable for "stretcher" patients; 203 (89%) had some protective
      equipment for staff but only 77 (34%) had complete protection--that is, goggles,
      chemical resistant clothing, and breathing apparatus. In the authors' opinion
      only seven (3%) departments had satisfactory premises and equipment to treat
      "stretcher" patients and full protection for staff. A further 11 (5%) departments
      were equipped to manage ambulant patients at a similar level. Some 205 (90%)
      departments stocked one or more antidotes to cyanide and 77 (34%) stocked all
      four antidotes. Thirty four (15%) departments held all four antidotes to cyanide
      and had full protection for staff. Only five (2%) departments had satisfactory
      premises and equipment to treat "stretcher" patients, full protection for staff,
      and at least three of four antidotes. CONCLUSIONS: Most departments had some
      equipment for chemical decontamination. However, there were major inconsistencies
      in the range of equipment held and these limited its usefulness. Only a small
      minority of departments was satisfactorily equipped to deal with a serious
      chemical incident.

PMID- 12205007
TI  - Non-cardiogenic pulmonary oedema in the course of verapamil intoxication.
AB  - Only three cases of non-cardiogenic pulmonary oedema secondary to high dose
      verapamil ingestion have been described in the literature. This report describes
      two girls, who developed pulmonary oedema in the course of massive dose verapamil
      ingestion (total of 6000 mg and 7200 mg). Left ventricule size and function was
      normal on transthoracic echocardiograms in both of these patients. They were
      treated successfully with mechanical ventilatory support. The report emphasises
      that this fatal complication may be seen with verapamil overdose and underlying
      mechanisms and therapeutic approach are discussed.

PMID- 12205008
TI  - An unusual presentation of a lumbar hernia.

PMID- 12205009
TI  - Two cases of biceps injury in bodybuilders with initially misleading
      presentation.
AB  - Two cases are reported of biceps injuries in body builders. In both cases the
      mechanism of injury is either unclear or initially misleading. One case went on
      to develop necrotising fasciitis, requiring extensive debridement after an
      initial diagnosis of a biceps haematoma. This report emphasises the difficulties
      inherent in differentiating necrotising and non-necrotising infections in the
      emergency department setting and highlights a subgroup of patients who may be at
      particular risk of delayed diagnosis.

PMID- 12205010
TI  - Flagellation: a rare cause of pneumothorax.

PMID- 12205011
TI  - The externally rotated leg: a trap for the unwary.

PMID- 12205012
TI  - Subcutaneous emphysema of the neck and colonic perforation.
AB  - Subcutaneous emphysema may result from pathological changes in the thorax or
      lung, as a result of localised infection with gas producing organisms, after
      abdominal procedures, or herald an intestinal perforation. The location and
      spread of extraperitoneal gas is determined by the anatomical barriers and fixed
      fascial layers surrounding the region of pathological change. The case highlights
      the extent of extraperitoneal gas after colonic perforation despite minimal
      clinical features and the importance of intra-abdominal causes of cervical
      subcutaneous emphysema.

PMID- 12205013
TI  - Traumatic pneumomammothorax.

PMID- 12205014
TI  - Failure of detection of pneumothorax on initial chest radiograph.
AB  - Failure to detect a pneumothorax may have serious complications. A case of a
      pneumothorax, which may have been overlooked if thoracic computed tomography had
      not been performed, is discussed.

PMID- 12205015
TI  - A strange case of a tension pneumothorax.

PMID- 12205016
TI  - A hemlock water dropwort curry: a case of multiple poisoning.

PMID- 12205017
TI  - Histamine fish poisoning: a common but frequently misdiagnosed condition.
AB  - Scombrotoxic or histamine fish poisoning is a common condition normally
      associated with consuming spoiled tuna, mackerel, bonito, or skipjack. Typical
      symptoms like flushing, urticaria, and palpitations mimic those of allergy so
      histamine fish poisoning can easily be misdiagnosed. Diagnosis is often clinical
      and the mainstay of treatment is antihistamines.

PMID- 12205018
TI  - Sudden visual loss after closed head injury.

PMID- 12205019
TI  - Fascicular tachycardia: uncommon or just unrecognised?

PMID- 12205020
TI  - Dead? Or just cold: profoundly hypothermic patient with no signs of life.
AB  - A 37 year old man was found in his garden cold with no signs of life. Pupils were
      fixed and dilated. Electrocardiography showed asystole initially. The paramedic
      crew started cardiopulmonary resuscitation and transferred him to the accident
      and emergency department. His temperature was 17.0 degrees C. Cardiopulmonary
      resuscitation was continued for three hours before rewarming using partial
      cardiopulmonary bypass. He eventually regained spontaneous cardiac output and
      made a full neurological recovery. Hypothermic patients with no evidence of life
      cannot be assumed to be dead as there is a chance of full recovery when fully
      warmed.

PMID- 12205021
TI  - Urgent contrast enhanced computed tomography in the diagnosis of acute bowel
      infarction.
AB  - Bowel infarction commonly presents as an acute abdomen that rapidly progresses to
      severe shock. The diagnosis is often not clinically suspected. Three cases are
      described where the diagnosis was made during dynamic contrast enhanced computed
      tomography (CT), when gas was demonstrated in the portal venous system and liver.
      Two patients died during surgery, the third survived because of the prompt
      diagnosis made on CT, and subsequent surgical treatment. The radiological
      findings are reviewed.

PMID- 12205022
TI  - Pseudomyocardial infarction associated with a retrocaecal gangrenous appendix.
AB  - The case is presented of a 54 year old man who attended the emergency department
      with a history of central abdominal pain and electrocardiograpic changes
      consistent with an anteroseptal myocardial infarction. Myocardial infarction was
      not confirmed with serial cardiac enzymes and a subsequent laparotomy revealed a
      gangrenous retrocaecal appendix. This case highlights the rare but recognised
      association between an acute surgical abdomen and pseudomyocardial infarction. It
      is, to the authors' knowledge, the first reported case of pseudomyocardial
      infarction complicating a retrocaecal appendicitis.

PMID- 12205023
TI  - Urinary schistosomiasis.

PMID- 12205024
TI  - Torsade de pointes.
AB  - A case is described of torsade de pointes in a 41 year old woman with pre
      existing QTc prolongation, potentially exacerbated by treatment with sotalol.
      Previous cardiac investigations had been normal and after a second episode of
      ventricular fibrillation the patient was referred for electrophysiological
      studies. The authors review the physiology, causes, and treatment of QTc
      prolongation and torsade de pointes.

PMID- 12205025
TI  - Muscle-derived interleukin-6: mechanisms for activation and possible biological
      roles.
AB  - It has recently been demonstrated that the marked increase in the systemic
      concentration of cytokine interleukin-6 (IL-6) seen with exercise originates from
      the contracting limb and that skeletal muscle cells per se are the likely source
      of the production. This review summarizes the possible mechanisms for activation
      and biological consequences of muscle-derived IL-6. It appears that intramuscular
      IL-6 is stimulated by complex signaling cascades initiated by both calcium (Ca2+)
      -dependent and -independent stimuli. It also seems likely that skeletal muscle
      produces IL-6 to aid in maintaining metabolic homeostasis during periods of
      altered metabolic demand such as muscular exercise or insulin stimulation. It may
      do so via local and/or systemic effects. This review also explores the efficacy
      that IL-6 may be used as a therapeutic drug in treating metabolic disorders such
      as obesity, type 2 diabetes, and atherosclerosis.

PMID- 12205026
TI  - The fetal origins of atherosclerosis: maternal hypercholesterolemia, and
      cholesterol-lowering or antioxidant treatment during pregnancy influence in utero
      programming and postnatal susceptibility to atherogenesis.
AB  - It has long been postulated that pathogenic events during fetal development
      influence atherosclerosis-related diseases later in life, but the mechanisms
      involved are unknown. This review focuses on the evidence indicating that
      maternal hypercholesterolemia during pregnancy is responsible for one cascade of
      pathogenic events. Maternal hypercholesterolemia is associated with greatly
      increased fatty streak formation in human fetal arteries and accelerated
      progression of atherosclerosis during childhood. Recent experiments in
      genetically more homogeneous rabbits established that temporary diet-induced
      maternal hypercholesterolemia is sufficient to enhance fetal lesion formation.
      More important, maternal hypercholesterolemia or ensuing pathogenic events in the
      fetus increase postnatal atherogenesis in response to hypercholesterolemia.
      Maternal treatment with cholesterol-lowering agents or antioxidants greatly
      reduces fetal and postnatal atherogenesis, indicating a pathogenic role of lipid
      peroxidation and a potential involvement of oxidation-sensitive signaling
      pathways. Experiments in a murine model showed that differences in arterial gene
      expression between offspring of normo- and hypercholesterolemic mothers persist
      long after birth, supporting the assumption that fetal lesion formation is
      associated with genetic programming, which may in turn affect postnatal
      atherogenesis. A better understanding of pathogenic programming events in utero
      may lead to the identification of genes determining the susceptibility to
      atherosclerosis and define novel preventive approaches.

PMID- 12205027
TI  - Persistence of microscopic human cancers in mice: alterations in the angiogenic
      balance accompanies loss of tumor dormancy.
AB  - Some human tumor lines do not form visible tumors when inoculated into
      immunosuppressed mice. The fate of these human tumor lines was followed by
      transfecting them with green fluorescence protein before inoculating them into
      mice. Although the tumor lines failed to grow progressively, they formed small
      dormant microscopic foci maintained at constant mass by balanced proliferation
      and apoptosis. Transfecting the cells with either VEGF165 or activated c-Ha-ras
      induced loss of dormancy, which correlated with a shift in the angiogenic balance
      toward increased vascularity with reduced tumor cell apoptosis. These results
      support a model in which loss of dormancy is controlled in part by a switch to an
      angiogenic phenotype. These tumor lines may serve as models for investigating the
      cellular mechanisms controlling dormancy and identifying those factors that
      promote the loss of balanced proliferation and apoptosis. Finally, these models
      may prove useful in the design and testing of therapies directed toward
      eradicating dormant tumors and preventing tumor recurrence.

PMID- 12205028
TI  - Role of transglutaminase 2 in glucose tolerance: knockout mice studies and a
      putative mutation in a MODY patient.
AB  - Transglutaminase 2 (TGase 2) is a Ca+2-dependent enzyme that catalyzes both
      intracellular and extracellular cross-linking reactions by transamidation of
      specific glutamine residues. TGase 2 is known to be involved in the membrane
      mediated events required for glucose-stimulated insulin release from the
      pancreatic beta cells. Here we show that targeted disruption of TGase 2 impairs
      glucose-stimulated insulin secretion. TGase 2-/- mice show glucose intolerance
      after intraperitoneal glucose loading. TGase 2-/- mice manifest a tendency to
      develop hypoglycemia after administration of exogenous insulin as a consequence
      of enhanced insulin receptor substrate 2 (IRS-2) phosphorylation. We suggest that
      the increased peripheral sensitivity to insulin partially compensates for the
      defective secretion in this animal model. TGase 2-/- mouse phenotype resembles
      that of the maturity-onset diabetes of young (MODY) patients. In the course of
      screening for human TGase 2 gene in Italian subjects with the clinical features
      of MODY, we detected a missense mutation (N333S) in the active site of the
      enzyme. Collectively, these results identify TGase 2 as a potential candidate
      gene in type 2 diabetes.

PMID- 12205029
TI  - cDNA array analysis of gene expression profiles in the striata of wild-type and
      Cu/Zn superoxide dismutase transgenic mice treated with neurotoxic doses of
      amphetamine.
AB  - Amphetamine (AMPH) is a drug of abuse that causes the degeneration of striatal
      dopamine terminals in mammals. Superoxide radicals seem to participate in AMPH
      induced damage because its toxicity is attenuated in Cu/Zn superoxide dismutase
      transgenic (SOD-tg) mice. To provide a detailed analysis of molecular changes
      associated with AMPH toxicity, we used cDNA arrays consisting of 1176 genes to
      detect differential changes in gene expression in the striata of wild-type and
      SOD-tg mice treated with neurotoxic doses of the drug. We found 42 genes that
      showed >1.8-fold changes in at least two consecutive time points during the
      course of the study and were differentially affected by AMPH in the two
      genotypes. Specifically, more transcription factors and genes involved in
      responses to injury/inflammation were affected in wild-type mice after AMPH
      administration. Some of these stimulant-induced superoxide-dependent alterations
      in gene expression might affect neuronal functions and promote neuronal damage.
      Other changes might help to provide some degree of protection against AMPH
      toxicity. These results support the view that the use of global array analysis of
      gene expression will help to identify novel molecular mediators of AMPH-induced
      neurodegeneration.

PMID- 12205030
TI  - Estrogen regulates development of the somatic cell phenotype in the eutherian
      ovary.
AB  - Steroids play a critical role in gonadal differentiation in birds, reptiles, and
      amphibia whereas gonadal differentiation in mammals is thought to be determined
      by genetic mechanisms. The gonads of female mice incapable of synthesizing
      estrogens due to disruption of the aromatase gene (ArKO) provide a unique model
      to test the role of estrogen in regulating the gonadal phenotype. We have shown
      that in the absence of estrogen, genetically female mice develop testicular
      tissue within their ovaries. The ovaries develop cells that possess structural
      and functional characteristics of testicular interstitial cells and of
      seminiferous tubule-like structures lined with Sertoli cells. Moreover, the
      ovaries express mRNA for the testis-specific Sertoli cell transcription factor
      Sox 9 and espin protein, which is specific for inter-Sertoli cell junctions. The
      development of the testicular tissue in this model can be reverted/postponed by
      replacing estrogen. When ArKO female mice were fed a diet containing
      phytoestrogens, the appearance of Leydig and Sertoli cells was postponed and
      reduced. Furthermore, administration of estradiol-17beta decreased the number of
      Sertoli and Leydig cells in the ovaries. These findings constitute definitive
      evidence that estrogen plays a critical role in maintaining female somatic
      interstitial and granulosa cells in the eutherian ovary.

PMID- 12205031
TI  - Modulation of renal Ca2+ transport protein genes by dietary Ca2+ and 1,25
      dihydroxyvitamin D3 in 25-hydroxyvitamin D3-1alpha-hydroxylase knockout mice.
AB  - Pseudovitamin D-deficiency rickets (PDDR) is an autosomal disease characterized
      by hyperparathyroidism, rickets, and undetectable levels of 1,25
      dihydroxyvitaminD3 (1,25(OH)2D3). Mice in which the 25-hydroxyvitamin D3-1alpha
      hydroxylase (1alpha-OHase) gene was inactivated presented the same clinical
      phenotype as patients with PDDR and were used to study renal expression of the
      epithelial Ca2+ channel (ECaC1), the calbindins, Na+/Ca2+ exchanger (NCX1), and
      Ca2+-ATPase (PMCA1b). Serum Ca2+ (1.20+/-0.05 mM) and mRNA/protein expression of
      ECaC1 (41+/-3%), calbindin-D28K (31+/-2%), calbindin-D9K (58+/-7%), NCX1 (10+/
      2%), PMCA1b (96+/-4%) were decreased in 1alpha-OHase-/- mice compared with 1alpha
      OHase+/- littermates. Feeding these mice a Ca2+-enriched diet normalized serum
      Ca2+ levels and expression of Ca2+ proteins except for calbindin-D9K expression.
      1,25(OH)2D3 repletion resulted in increased expression of Ca2+ transport proteins
      and normalization of serum Ca2+ levels. Localization of Ca2+ transport proteins
      was clearly polarized in which ECaC1 was localized along the apical membrane,
      calbindin-D28K in the cytoplasm, and calbindin-D9K along the apical and
      basolateral membranes, resulting in a comprehensive mechanism facilitating renal
      transcellular Ca2+ transport. This study demonstrated that high dietary Ca2+
      intake is an important regulator of the renal Ca2+ transport proteins in
      1,25(OH)2D3-deficient status and thus contributes to the normalization of blood
      Ca2+ levels.

PMID- 12205032
TI  - NMDA sensitization and stimulation by peroxynitrite, nitric oxide, and organic
      solvents as the mechanism of chemical sensitivity in multiple chemical
      sensitivity.
AB  - Multiple chemical sensitivity (MCS) is a condition where previous exposure to
      hydrophobic organic solvents or pesticides appears to render people
      hypersensitive to a wide range of chemicals, including organic solvents. The
      hypersensitivity is often exquisite, with MCS individuals showing sensitivity
      that appears to be at least two orders of magnitude greater than that of normal
      individuals. This paper presents a plausible set of interacting mechanisms to
      explain such heightened sensitivity. It is based on two earlier theories of MCS:
      the elevated nitric oxide/peroxynitrite theory and the neural sensitization
      theory. It is also based on evidence implicating excessive NMDA activity in MCS.
      Four sensitization mechanisms are proposed to act synergistically, each based on
      known physiological mechanisms: Nitric oxide-mediated stimulation of
      neurotransmitter (glutamate) release; peroxynitrite-mediated ATP depletion and
      consequent hypersensitivity of NMDA receptors; peroxynitrite-mediated increased
      permeability of the blood-brain barrier, producing increased accessibility of
      organic chemicals to the central nervous system; and nitric oxide inhibition of
      cytochrome P450 metabolism. Evidence for each of these mechanisms, which may also
      be involved in Parkinson's disease, is reviewed. These interacting mechanisms
      provide explanations for diverse aspects of MCS and a framework for hypothesis
      driven MCS research.

PMID- 12205034
TI  - In vivo gene transfer of soluble TNF-alpha receptor 1 alleviates myocardial
      infarction.
AB  - Apoptosis is the major independent form of cardiomyocyte cell death in acute
      myocardial infarction (AMI). TNF-alpha release early in the course of AMI
      contributes to myocardial injury, and TNF-alpha induces apoptosis in
      cardiomyocytes. Soluble TNF-alpha receptor 1 (sTNFR1) is an antagonist to TNF
      alpha. However, the effect of sTNFR1 on AMI remains unclear. Here we report that
      direct injection of an sTNFR1 expression plasmid DNA to the myocardium reduces
      infarct size in experimental rat AMI. Treatment with sTNFR1 expression plasmid
      DNA reduced the TNF-alpha bioactivity in the myocardium and the apoptosis of
      cardiomyocytes. These findings suggest that the anti-TNF-alpha therapy by sTNFR1
      can be a new strategy for treatment of AMI.

PMID- 12205033
TI  - Androgen receptor with elongated polyglutamine tract forms aggregates that alter
      axonal trafficking and mitochondrial distribution in motor neuronal processes.
AB  - The CAG/polyglutamine (polyGln)-related diseases include nine different members
      that together form the most common class of inherited neurodegenerative
      disorders; neurodegeneration is linked to the same type of mutation, found in
      unrelated genes, consisting of an abnormal expansion of a polyGln tract normally
      present in the wild-type proteins. Nuclear, cytoplasmic, or neuropil aggregates
      are detectable in CAG/polyGln-related diseases, but their role is still debated.
      Alteration of the androgen receptor (AR), one of these proteins, has been linked
      to spinal and bulbar muscular atrophy, an X-linked recessive disease
      characterized by motoneuronal death. By using immortalized motoneuronal cells
      (the neuroblastoma-spinal cord cell line NSC34), we analyzed neuropil aggregate
      formation and toxicity: green fluorescent protein-tagged wild-type or mutated ARs
      were cotransfected into NSC34 cells with a blue fluorescent protein tagged to
      mitochondria. Altered mitochondrial distribution was observed in neuronal
      processes containing aggregates; occasionally, neuropil aggregates and
      mitochondrial concentration corresponded to axonal swelling. Neuropil aggregates
      also impaired the distribution of the motor protein kinesin. These data suggest
      that neuropil aggregates may physically alter neurite transport and thus deprive
      neuronal processes of factors or components that are important for axonal and
      dendritic functions. The soma may then be affected, leading to neuronal
      dysfunctions and possibly to cell death.

PMID- 12205035
TI  - Mechanical stress-induced DNA damage and rac-p38MAPK signal pathways mediate p53
      dependent apoptosis in vascular smooth muscle cells.
AB  - Recently, we demonstrated that biomechanical stress induces apoptosis of vascular
      smooth muscle cells (SMCs) (Mayr et al., FASEB J. 2000; 15:261-270). In this
      article we investigated the molecular mechanisms of mechanical stress-induced
      apoptosis. When SMCs were subjected to cyclic strain, tumor-suppressor p53 was
      activated as evidenced by gel mobility shift assays and Western blot analyses.
      p53 activation was largely attenuated if SMCs were pretreated with SB202190, a
      specific p38MAPK inhibitor, or were stably transfected with dominant negative
      rac, an upstream signal transducer of p38MAPK pathways. Kinase assays provided
      direct evidence that p38MAPKs phosphorylated p53 within 30 min of cyclic strain.
      Additionally, mechanical stress resulted in oxidative DNA damage as detected by
      the presence of 8-oxoguanine. Treatment with the antioxidant U-74389G abrogated
      p53 activation. p53 activation was followed by expression and mitochondrial
      translocation of the proapoptotic protein Bax. Likewise, mechanical stress
      resulted in up-regulation of anti-apoptotic Bcl-2 proteins, including Bcl-2 and
      Bcl-xL. However, a marked loss of mitochondrial membrane potential occurred in
      wild-type, but not in p53-/-, SMCs. The latter lost their ability to express Bax
      and showed no apoptosis in response to cyclic strain. Taken together, our data
      provide the first evidence that SMC apoptosis induced by mechanical stress is p53
      dependent.

PMID- 12205036
TI  - Gene delivery by a steroid-peptide nucleic acid conjugate.
AB  - We previously introduced a method called steroid-mediated gene delivery (SMGD),
      which uses steroid receptors as shuttles to facilitate the nuclear uptake of
      transfected DNA. Here, we describe a SMGD strategy with peptide nucleic acids
      (PNAs) that allowed linkage of a steroid molecule to a defined position in a
      plasmid without disturbing its gene expression. We synthesized and tested several
      bifunctional steroid derivatives [patent in process of nationalization] and
      finally selected the compound named DEX-bisPNA, a molecule consisting of a
      dexamethasone moiety linked to a PNA clamp (bisPNA) through a 30-atom chemical
      spacer. Dex-bisPNA binds to the glucocorticoid receptor (GR) as well as to
      reporter plasmids containing the corresponding PNA binding sites, translocates
      the GR from the cytoplasm into the nucleus, and increases the delivery of plasmid
      to the nucleus, resulting in enhanced GR-dependent expression of the reporter
      gene. The SMGD effect was more pronounced in growth-arrested cells than in
      proliferating cells. The specificity for the GR was shown by the reversion of the
      SMGD effect in the presence of dexamethasone as well as an enhanced expression in
      GR-positive cells but not in GR-negative cells. Thus, SMGD with PNA is a
      promising strategy for nonviral gene delivery into target tissues expressing
      specific steroid receptors.

PMID- 12205037
TI  - The human prostate cancer cell line LNCaP bears functional membrane testosterone
      receptors that increase PSA secretion and modify actin cytoskeleton.
AB  - Recent findings have shown that, in addition to the genomic action of steroids,
      through intracellular receptors, short-time effects could be mediated through
      binding to membrane sites. In the present study of prostate cancer LNCaP cells,
      we report that dihydrotestosterone and the non-internalizable analog testosterone
      BSA increase rapidly the release of prostate-specific antigen (PSA) in the
      culture medium. Membrane testosterone binding sites were identified through
      ligand binding on membrane preparations, flow cytometry, and confocal laser
      microscopy of the non-internalizable fluorescent analog testosterone-BSA-FITC, on
      whole cells. Binding on these sites is time- and concentration-dependent and
      specific for testosterone, presenting a KD of 10.9 nM and a number of 144
      sites/mg protein (approximately 13000 sites/cell). Membrane sites differ
      immunologically for intracellular androgen receptors. The secretion of PSA after
      membrane testosterone receptor stimulation was inhibited after pretreatment with
      the actin cytoskeleton disrupting agent cytochalasin B. In addition, membrane
      testosterone binding modifies the intracellular dynamic equilibrium of monomeric
      to filamentous actin and remodels profoundly the actin cytoskeleton organization.
      These results are discussed in the context of a possible involvement of these
      sites in cancer chemotherapy.

PMID- 12205038
TI  - Innervation-dependent phosphorylation and accumulation of alphaB-crystallin and
      Hsp27 as insoluble complexes in disused muscle.
AB  - Levels and phosphorylation states of the two small molecular chaperones, alphaB
      crystallin and Hsp27, in disused rat soleus muscles were determined by Western
      blot analysis of extracts with antibodies recognizing each of the two proteins
      and their phosphorylated serine residues. Increased phosphorylation and
      relocalization to insoluble fractions were found within a few days of hind-limb
      suspension. High phosphorylation of alphaB-crystallin at Ser-59 (and to a certain
      extent, at Ser-45) and of Hsp27 at Ser-15 and Ser-85, along with phosphorylated,
      active states of p38 and p44/42 mitogen-activated protein kinases were maintained
      during hind-limb suspension but promptly returned to control levels within a 5
      day recovery period. These results are similar to those observed with U373 MG
      glioma cells exposed to proteasome inhibitors (16). However, the responses of
      alphaB-crystallin and Hsp27 in suspended soleus muscles did not appear with
      ipsilateral transection of the sciatic nerve trunk, indicating mediation by nerve
      activity. The fact that ubiquitinated proteins accumulated in the insoluble
      fractions of suspended soleus muscle further suggests participation of alphaB
      crystallin and Hsp27 in quality control of proteins in disused soleus muscle,
      with involvement of nerve activity-dependent processes.

PMID- 12205039
TI  - Protein kinase C-epsilon mediates bradykinin-induced cyclooxygenase-2 expression
      in human airway smooth muscle cells.
AB  - We previously reported that proinflammatory mediator bradykinin (BK) induces
      cyclooxygenase (COX)-2 expression in human airway smooth muscle (HASM), but the
      mechanism is unknown in any biological system. Here, we studied the role of
      specific protein kinase C (PKC) isozyme(s) in COX-2 expression. Among the eight
      PKC isozymes present in HASM cells, the Ca2+-independent PKC-delta and -epsilon
      and the Ca2+-dependent PKC-alpha and -betaI were translocated to the nucleus upon
      BK stimulation. BK-induced COX-2 expression and prostaglandin E2 (PGE2)
      accumulation were mimicked by the direct PKC activator phorbol 12-myristate 13
      acetate (PMA) and inhibited by the broad spectrum PKC inhibitor
      bisindolylmaleimide I. However, the selective Ca2+-dependent PKC isozyme
      inhibitor Go 6976 had no effect. Furthermore, the membrane-permeable calcium
      chelator BAPTA-AM had no effect on BK-induced COX-2 expression and COX activity
      despite its inhibition of PGE2 accumulation, suggesting the involvement of Ca2+
      independent PKC isozymes. Rottlerin, a PKC-delta inhibitor, also had no effect,
      likely implicating PKC-epsilon. BK-stimulated transcriptional activation of a COX
      2 promoter reporter construct was enhanced by overexpression of wild-type PKC
      epsilon and abolished by a dominant negative PKC-epsilon, but it was not affected
      by wild-type or dominant negative PKC-alpha or -delta. Collectively, our results
      demonstrate that PKC-e mediates BK-induced COX-2 expression in HASM cells.

PMID- 12205040
TI  - Differential effects of leptin on thermoregulation and uncoupling protein
      abundance in the neonatal lamb.
AB  - As the role of leptin in energy balance in neonate is unknown, we investigated
      the effect of acute (2 h) and chronic (7 days) administration of leptin (100
      microg/day) on thermoregulation and mitochondrial protein abundance in adipose
      tissue. The concentration of uncoupling protein (UCP)1 and voltage-dependent
      anion channel (VDAC) located on the inner and outer mitochondrial membranes,
      respectively, were measured. Administration of leptin prevented the normal
      decline in colonic temperature over the first few hours and days after birth. It
      subsequently accelerated the loss of both mRNA and protein for UCP1 but had no
      effect on VDAC abundance. At seven days of age, colonic temperature was
      correlated strongly with both mRNA abundance and thermogenic potential of UCP1 in
      leptin-treated but not control lambs, indicating more effective use of UCP1 for
      heat production following leptin administration. Leptin had no effect on weight
      gain or adipose tissue deposition; at one day of age only, leptin mRNA was
      correlated positively with adipose tissue weight. In conclusion, leptin
      administration to neonatal lambs improves thermoregulation and promotes the loss
      of UCP1 in brown adipose tissue.

PMID- 12205041
TI  - Extracellular signal-regulated kinases phosphorylate 5-lipoxygenase and stimulate
      5-lipoxygenase product formation in leukocytes.
AB  - 5-lipoxygenase (5-LO) is the key enzyme in the biosynthesis of proinflammatory
      leukotrienes. Here, we demonstrate that extracellular signal-regulated kinases
      (ERKs) can phosphorylate 5-LO in vitro. Efficient phosphorylation required the
      presence of unsaturated fatty acids and was abolished when Ser-663 was mutated to
      alanine. In intact HeLa cells stimulated with arachidonic acid (AA), impaired 5
      LO product formation was evident in cells expressing the S663A-5-LO mutant
      compared with cells expressing wild-type 5-LO. For Mono Mac 6 cells, priming with
      phorbol myristate acetate (PMA) before stimulation with ionophore was required
      for ERK1/2 activation and efficient 5-LO phosphorylation, in parallel with
      substantial AA release and 5-LO product formation. Inhibition of PKC by GF109203x
      or MEK1/2 by U0126 (or PD98059) abolished the 5-LO up-regulation effects of PMA.
      In contrast, these inhibitors failed to suppress 5-LO product formation induced
      by stimuli such as AA plus ionophore, which apparently do not involve the ERK1/2
      pathway. Based on inhibitor studies, ERKs are also involved in AA-stimulated 5-LO
      product formation in PMNL, whereas a role for ERKs is not apparent in 5-LO
      activation induced by ionophore or cell stress. Finally, the data suggest that
      ERKs and p38 MAPK-regulated MAPKAPKs can act in conjunction to stimulate 5-LO by
      phosphorylation.

PMID- 12205042
TI  - Development of hepatocytes from ES cells after transfection with the HNF-3beta
      gene.
AB  - We have attempted to generate embryonic stem (ES) cell-derived hepatocytes
      expressing liver-specific functional properties by use of ES cell technology. It
      was found that ES cells are allowed to differentiate into hepatocytes possessing
      high metabolic activities when hepatocyte nuclear factor (HNF)-3beta-transfected
      ES cells are cultured in alpha-MEM medium supplemented with 10% fetal bovine
      serum (FBS) and fibroblast growth factor (FGF)-2 in the three-dimensional cell
      culture system at 5% CO2. The differentiated cells induced albumin,
      triacylglycerol, urea, and glycogen synthesis as well as further expression of
      metabolic proteins and serum factors as markers of hepatocytic differentiation
      for at least 4 months. The cells differentiated from HNF-3beta-transfected ES
      cells also had hepatocyte-like ultrastructural characteristics, including several
      endoplasmic reticula, mitochondrion, and glycogen. Our findings indicate that
      generation of hepatocytes maintaining high metabolic functions developed from
      mouse ES cells will facilitate the study of the basic mechanism for hepatogenesis
      and will certainly provide new opportunities for tissue transplantation.

PMID- 12205043
TI  - Conjugated linoleic acids (CLAs) regulate the expression of key apoptotic genes
      in human breast cancer cells.
AB  - Conjugated linoleic acid (CLA) reduces mammary tumorigenesis in rodent models,
      induces apoptosis in rodent mammary tumor cell lines, and decreases expression of
      antiapoptotic bcl-2 in rat mammary tissue. This investigation focused on the cell
      mechanisms underlying the antitumor effects of CLA. Changes (mRNA, protein) in
      expression of major proapoptotic p53, p21WAF1/CIP1, bax, bcl-Xs genes, and the
      antiapoptotic bcl-2 gene were observed in malignant MCF-7 and MDA-MB-231 cells
      and in benign MCF-10a human mammary tumor cells in culture. CLA, but not linoleic
      acid (LA), inhibited proliferation in all cells; CLA mix was most effective. CLA
      increased DNA damage (apoptosis). CLA increased mRNA expression of p53 and
      p21WAF1/CIP1 (three- to fivefold and twofold, respectively) but either decreased
      bcl-2 by 20-30% or had no effect in MCF-7 and MCF-10a cells, respectively;
      protein expression reflected mRNA values. In MDA-MBA-231 (mutant p53) cells, mRNA
      for p53 was not changed, but p21WAF1/CIP1 and bcl-2 mRNA was increased. Protein
      expression largely reflected mRNA changes but, surprisingly, CLA completely
      suppressed mutant p53 protein in MDA-MB-231 cells. Apparent antiapoptotic effects
      of increased bcl-2 expression in MDA-MBA-231 cells were countered by increased
      proapoptotic p21WAF1/CIP1, Bax, and Bcl-Xs proteins. Findings indicate that CLA
      elicits mainly proapoptotic effects in human breast tumor cells through both p53
      dependent and p53-independent pathways, according to cell type.

PMID- 12205044
TI  - Human TNF-alpha in transgenic mice induces differential changes in redox status
      and glutathione-regulating enzymes.
AB  - Tumor necrosis factor a (TNF-alpha) is a pleiotropic cytokine involved in several
      diseases. Various effects of TNF-alpha are mediated by the induction of a
      cellular state consistent with oxidative stress. Glutathione (GSH) is a major
      redox-buffer of eukaryotic cells and is important in the defense against
      oxidative stress. We hypothesized that persistent TNF-alpha secretion could
      induce oxidative stress through modulation of GSH metabolism. This hypothesis was
      examined in a transgenic mouse model with low, persistent expression of human TNF
      alpha in the T cell compartment. Major findings were i) marked tissue-specific
      changes in GSH redox status and GSH regulating enzymes, with the most pronounced
      changes in liver; ii) moderate changes in GSH metabolism and up-regulation of GSH
      regulating enzymes were observed in lung and kidney from transgenic mice; and
      iii) liver, lung and kidney from transgenic mice had decreased levels of total
      glutathione, whereas splenic CD4+ and CD8+ T cells had a marked increase in
      oxidized glutathione as the major change. Oxidative stress induced by persistent
      low-grade exposure to TNF-alpha in transgenic mice appears to involve marked
      organ-specific alterations in glutathione redox status and glutathione-regulating
      enzymes with the most pronounced changes in the liver. These mice constitute a
      useful model for immunodeficiency syndromes and chronic inflammatory diseases
      involving pathogenic interaction between TNF-alpha and oxidative stress.

PMID- 12205045
TI  - Bcl-2 overexpression in human melanoma cells increases angiogenesis through VEGF
      mRNA stabilization and HIF-1-mediated transcriptional activity.
AB  - The aim of this paper was to study the molecular mechanisms by which bcl-2
      increases hypoxia-induced vascular endothelial growth factor (VEGF) expression.
      We demonstrated that bcl-2 overexpression in M14 human melanoma cell line
      enhances hypoxia-induced VEGF mRNA stability and promoter activation. In
      particular, the half-life of the message was longer in bcl-2 transfectants
      (approximately 330 min) than in control cells (approximately 180 min). In
      addition, bcl-2 overexpression increased VEGF promoter activity through the
      hypoxia-inducible factor-1 (HIF-1) transcription factor. Increased HIF-1a protein
      expression and DNA binding activity were detected in bcl-2 overexpressing cells
      compared with control cells. An enhanced functional activity of secreted VEGF was
      found both in in vitro and in vivo angiogenic assays, and the use of VEGF
      specific antibodies validated the role of VEGF on bcl-2-induced angiogenesis.
      Taken together our results indicate that bcl-2 plays an important role in
      melanoma angiogenesis, and that VEGF mRNA stabilization and HIF-1-mediated
      transcriptional activity are two important control points in bcl-2/hypoxia
      induced VEGF expression.

PMID- 12205046
TI  - 3H-thymidine is a defective tool with which to measure rates of DNA synthesis.
AB  - Metabolic incorporation of 3H-thymidine into cellular DNA is a widely used
      protocol to monitor rates of DNA synthesis and cell proliferation. However, this
      radiochemical has also been reported to induce cell-cycle arrest and apoptosis in
      addition to DNA damage. Using stable isotope-labeled thymidine, we demonstrate
      that 3H-thymidine induces dose-dependent inhibition of the rate of DNA synthesis.
      This inhibition occurred within the first round of replication after addition of
      the radiolabeled tracer and demonstrates the cytotoxic effects of conventional
      doses of 3H-thymidine (typically greater than or equal to 1 microCi/ml). These
      results thus show that stable isotope methods are superior to radioisotopes for
      determining rates of DNA synthesis and cell replication. Because 3H-thymidine
      perturbs the very process it was employed to study, experiments using 3H
      thymidine to monitor DNA synthesis and cell proliferation should be interpreted
      with caution.

PMID- 12205047
TI  - Cleavage of hemoglobin by hookworm cathepsin D aspartic proteases and its
      potential contribution to host specificity.
AB  - Hookworms routinely reach the gut of nonpermissive hosts but fail to successfully
      feed, develop, and reproduce. To investigate the effects of host-parasite
      coevolution on the ability of hookworms to feed in nonpermissive hosts, we cloned
      and expressed aspartic proteases from canine and human hookworms. We show here
      that a cathepsin D-like protease from the canine hookworm Ancylosotoma caninum
      (Ac-APR-1) and the orthologous protease from the human hookworm Necator
      americanus (Na-APR-1) are expressed in the gut and probably exert their
      proteolytic activity extracellularly. Both proteases were detected
      immunologically and enzymatically in somatic extracts of adult worms. The two
      proteases were expressed in baculovirus, and both cleaved human and dog
      hemoglobin (Hb) in vitro. Each protease digested Hb from its permissive host
      between twofold (whole molecule) and sixfold (synthetic peptides) more
      efficiently than Hb from the nonpermissive host, despite the two proteases'
      having identical residues lining their active site clefts. Furthermore, both
      proteases cleaved Hb at numerous distinct sites and showed different substrate
      preferences. The findings suggest that the paradigm of matching the molecular
      structure of the food source within a host to the molecular structure of the
      catabolic proteases of the parasite is an important contributing factor for host
      parasite compatibility and host species range.

PMID- 12205048
TI  - Glycosulfopeptides modeled on P-selectin glycoprotein ligand 1 inhibit P-selectin
      dependent leukocyte rolling in vivo.
AB  - Leukocytic inflammation can be limited by inhibiting selectin-dependent leukocyte
      rolling. In spite of intensive efforts to develop small molecule selectin
      inhibitors with defined structure-activity profiles, inhibition of P-selectin
      dependent leukocyte rolling in vivo by such a compound has yet to be described.
      We recently reported that glycosulfopeptides (GSP), modeled on the high affinity
      selectin ligand PSGL-1, inhibit leukocyte binding to P-selectin in vitro. Here,
      we have used intravital microscopy to investigate whether GSP can inhibit P
      selectin-dependent leukocyte rolling in vivo. Surgical preparation of the mouse
      cremaster muscle for intravital microscopy induced P-selectin-dependent leukocyte
      rolling. Baseline rolling was recorded for 1 min followed by i.v. injection of
      GSP. 2-GSP-6 and 4-GSP-6 substantially reversed P-selectin-dependent leukocyte
      rolling, whereas control GSP, which are not fully glycosylated, did not.
      Inhibition of leukocyte rolling by 2- and 4-GSP-6 lasted 2-4 min. Clearance
      studies with 125I-labeled 4-GSP-6 demonstrated rapid reduction in its circulating
      levels concurrent with accumulation in urine. These data represent the first
      demonstration that a precisely defined structure based on a natural P-selectin
      ligand can inhibit P-selectin-dependent leukocyte rolling in vivo.

PMID- 12205049
TI  - Polycyclic aromatic hydrocarbons present in cigarette smoke cause endothelial
      cell apoptosis by a phospholipase A2-dependent mechanism.
AB  - Smoking is a major risk factor for endothelial cell injury and subsequent
      coronary artery disease. Epidemiological studies implicate the phospholipase
      A2/arachidonic acid cascade in the mechanism by which smoking causes heart
      disease. However, specific components of cigarette smoke that activate this
      pathway have not been identified. The purpose of this study was to investigate
      the effects of polycyclic aromatic hydrocarbons contained in cigarette smoke on
      phospholipase A2 (PLA2) activity and apoptosis of human coronary artery
      endothelial cells. 1-methylanthracene (1-MA), phenanthrene (PA), and
      benzo(a)pyrene (B(a)P) caused significant release of 3H-arachidonate from
      endothelial cells. 1-MA and PA, but not B(a)P, also caused significant release of
      3H-linoleic acid. Release of fatty acids from membrane phospholipids preceded the
      onset of apoptosis. 3H-arachidonate release and apoptosis induced by 1-MA, B(a)P,
      and PA were inhibited by methylarachidonoyl-fluorophosphonate, an inhibitor of
      Groups IV and VI PLA2s. Bromoenol lactone, an inhibitor of Group VI enzymes,
      inhibited both 3H-arachidonate release and apoptosis induced by 1-MA and PA, but
      not B(a)P. MJ33, an inhibitor of the acidic calcium-independent PLA2, attenuated
      3H-arachidonate release and apoptosis by PA, but not 1-MA or B(a)P. The presence
      of Groups IV and VI and the acidic iPLA2 in endothelial cells was demonstrated by
      reverse transcriptase-polymerase chain reaction and Western analysis. These data
      suggest that 1-MA, B(a)P and PA induce apoptosis of endothelial cells by a
      mechanism that involves activation of these three distinct isoforms of PLA2.

PMID- 12205050
TI  - Reduced tumor growth, experimental metastasis formation, and angiogenesis in rats
      with a hyperreactive dopaminergic system.
AB  - Outgrowth of solid tumors requires blood supply to the tumor. Tumor angiogenesis
      is dependent on the interplay between tumor-derived angiogenic factors and
      stromal cells. Recently, it has been shown that the neurotransmitter dopamine is
      a potent inhibitor of VEGF-induced angiogenesis. Moreover, there is evidence that
      patients with schizophrenia have a hyperreactive dopaminergic system and are
      relatively protected from cancer. We hypothesized that hyperreactivity of the
      dopaminergic system is related to reduced angiogenesis and tumor development.
      Therefore, we investigated tumor growth and angiogenesis in two lines of Wistar
      rats with high (APO-SUS) or low (APO-UNSUS) dopaminergic reactivity. Subcutaneous
      implants of mammary adenocarcinoma cells (MADB106) in matrigel remained 35%
      smaller in APO-SUS rats than in APO-UNSUS rats (P<0.01). Moreover, APO-SUS rats
      developed less lung metastases after i.v. administration of MADB106 tumor cells.
      Furthermore, hemoglobin content (APO-SUS: 40.6+/-7.6; APO-UNSUS: 76.9+/-13 mg/dl,
      P<0.05) and expression of the endothelial determinant PECAM-1 in tumors from APO
      SUS rats were reduced (APO-SUS: 37+/-18; APO-UNSUS 69+/-25 units, P<0.01),
      indicating that reduced angiogenesis is responsible for reduced tumor development
      in APO-SUS rats. These results suggest a novel link between dopaminergic
      reactivity, angiogenesis, and tumor development and may explain part of the
      individual differences in cancer progression.

PMID- 12205051
TI  - Delta opioid agonists and volatile anesthetics facilitate cardioprotection via
      potentiation of K(ATP) channel opening.
AB  - Opioids and volatile anesthetics produce marked cardioprotective effects against
      myocardial infarction via the activation of ATP-sensitive potassium (K(ATP))
      channels, however, the effect of combined treatment with both drugs is unknown.
      We examined the hypothesis that opioids and volatile anesthetics potentiate
      cardiac K(ATP) channel opening, thereby enhancing cardioprotection. Rats were
      treated with the delta opioid agonists, TAN-67 or BW373U86, or isoflurane,
      together or alone with and without diazoxide, a mitochondrial K(ATP) channel
      opener. Glibenclamide, a non-selective K(ATP) channel blocker, was used to
      further characterize the signaling mechanism involved. Myocardial infarct size
      (IS) was determined by tetrazolium staining and was expressed as a percent of the
      area at risk (AAR). High doses of TAN-67 (10 mg/kg), diazoxide (10 mg/kg), and
      isoflurane (1 MAC) produced a significant reduction in IS compared with the
      control group (30+/-3%, 36+/-5%, and 42+/-2 vs. 58+/-2%, respectively), whereas
      lower doses of the drugs had no effect except for the low dose of isoflurane (0.5
      MAC). The combination of TAN-67 and diazoxide or isoflurane and diazoxide
      resulted in a marked reduction in IS compared with controls in the presence of
      high (9+/-3% and 14+/-3%) and low (17+/-7% and 31+/-7%) dose combinations,
      respectively. The combination of TAN-67 or BW373U86 and isoflurane also caused a
      striking reduction in IS/AAR (16+/-7% and 7+/-2%, respectively). To date, this is
      the first demonstration that opioids and volatile anesthetics work in conjunction
      to confer protection against myocardial infarction through potentiation of
      cardiac K(ATP) channel opening.

PMID- 12205052
TI  - Interleukin-1alpha promotes angiogenesis in vivo via VEGFR-2 pathway by inducing
      inflammatory cell VEGF synthesis and secretion.
AB  - During inflammation, functional changes occur in the vasculature, including
      extensive endothelial cell mitotic activity and remodeling of capillaries.
      Interleukin-1alpha (IL-1alpha)is a prototypical proinflammatory cytokine.
      Vascular endothelial growth factor (VEGF) is a strong endothelial cell-specific
      mitogen that exerts a pivotal role in angiogenesis under physiological and
      pathological conditions. We show that IL-1alpha stimulates VEGF secretion by
      human peripheral blood mononuclear cells (PBMNCs) in a dose-dependent manner.
      This represents induction of de novo VEGF synthesis, as an induction of VEGF mRNA
      was observed. Also, the release of VEGF was blocked by cycloheximide. Reverse
      transcription-polymerase chain reaction (RT-PCR) detected four VEGF splice
      variants in unstimulated and in IL-1alpha-stimulated PBMNCs. In vivo in mice,
      subcutaneously administered IL-1alpha caused a strong local angiogenic response,
      which was accompanied by an infiltrate of VEGF-expressing inflammatory cells. The
      angiogenic effect of IL-1a was blocked when the mice were treated with VEGF
      receptor 2 (VEGFR-2) neutralizing antibodies. VEGFR-1 blocking antibodies had a
      marginal inhibitory effect on IL-1alpha-induced angiogenesis. These observations
      indicate that IL-1alpha induces angiogenesis by activating the VEGF-VEGFR-2
      signaling pathway between inflammatory cells and blood vessel endothelial cells.
      This novel mechanism of IL-1alpha-action may enhance the shift to angiogenic
      phenotype in various conditions designated by excessive angiogenesis.

PMID- 12205053
TI  - Mice deficient in TNF receptors are protected against dopaminergic neurotoxicity:
      implications for Parkinson's disease.
AB  - The pathogenic mechanisms underlying idiopathic Parkinson's disease (PD) remain
      enigmatic. Recent findings suggest that inflammatory processes are associated
      with several neurodegenerative disorders, including PD. Enhanced expression of
      the proinflammatory cytokine, tumor necrosis factor (TNF)-alpha, has been found
      in association with glial cells in the substantia nigra of patients with PD. To
      determine the potential role for TNF-alpha in PD, we examined the effects of the
      1-methyl-4-phenyl-1,2,3,4-tetrahydropyridine (MPTP), a dopaminergic neurotoxin
      that mimics some of the key features associated with PD, using transgenic mice
      lacking TNF receptors. Administration of MPTP to wild-type (+/+) mice resulted in
      a time-dependent expression of TNF-alpha in striatum, which preceded the loss of
      dopaminergic markers and reactive gliosis. In contrast, transgenic mice carrying
      homozygous mutant alleles for both the TNF receptors (TNFR-DKO), but not the
      individual receptors, were completely protected against the dopaminergic
      neurotoxicity of MPTP. The data indicate that the proinflammatory cytokine TNF
      alpha is an obligatory component of dopaminergic neurodegeneration. Moreover,
      because TNF-alpha is synthesized predominantly by microglia and astrocytes, our
      findings implicate the participation of glial cells in MPTP-induced
      neurotoxicity. Similar mechanisms may underlie the etiopathogenesis of PD.

PMID- 12205054
TI  - HIV-1 in peripheral blood monocytes: an underrated viral source.

PMID- 12205055
TI  - Genetic characterization of the fusidic acid and cadmium resistance determinants
      of Staphylococcus aureus plasmid pUB101.
AB  - We report the cloning of the fusidic acid and cadmium resistance determinants
      from Staphylococcus aureus plasmid pUB101. The pUB101 fusidic acid resistance
      determinant was located on a 2.9 kb HindIII fragment. Sequencing of this fragment
      revealed three putative open reading frames (ORFs) of 213 (far1), 152 (orf152)
      and 170 amino acids (orf170), which are flanked by the right-hand end of
      insertion sequence IS431/257 (IS431/257RH) and a partial ORF. Far1 and Orf152
      demonstrated homology with a chromosomally encoded fibronectin-binding protein of
      Listeria monocytogenes and the putative protein YosT, found on the SP beta c2
      prophage of Bacillus subtilis, respectively. Transformation of S. aureus with a
      construct containing a 949 bp far1-specific amplicon led to the isolation of a
      fusidic acid-resistant transformant, thereby identifying the pUB101 fusidic acid
      resistance structural gene. Between orf152 and far1 we identified a unique 113 bp
      symmetrical element and other repeat elements that may be involved with the
      control of orf152 and/or far1 expression. Hybridization of Southern blots
      revealed that far1 was not located on the chromosome or plasmid content of a
      limited number of Australian, UK and Hong Kong fusidic acid-resistant isolates.
      The pUB101 cadmium resistance determinant was located on a 3.6 kb HindIII
      fragment that carried a cadDX operon, remnants of two putative plasmid
      replication protein genes and IS431/257RH. Sequence analysis also demonstrated
      the presence of a single-stranded origin of replication, normally found on
      rolling circle replicating plasmids, within the putative promoter region of the
      cadDX operon.

PMID- 12205056
TI  - Multilocus sequence typing (MLST) shows that the 'Iberian' clone of methicillin
      resistant Staphylococcus aureus has spread to France and acquired reduced
      susceptibility to teicoplanin.
AB  - Infection by methicillin-resistant Staphylococcus aureus (MRSA) presents a
      serious problem, as these organisms are resistant to a wide range of antibiotics.
      Moreover, MRSA with reduced susceptibility to glycopeptides (GISA) have emerged
      in recent years. In our hospital we were faced with an outbreak of GISA between
      January and March 2000, involving six patients who were free of MRSA when the
      GISA isolate emerged, and five of whom had not been given glycopeptides. The
      initial GISA isolate from the six patients was compared with six 'historical'
      multiple-resistant MRSA isolates (1996-1999), which had not been found to be GISA
      by the routinely used method. Antibiotic susceptibility was studied through the
      disc diffusion method, and MICs of glycopeptides were determined by Etest, agar
      and broth dilution techniques. Molecular strain typing was done by PFGE and
      multilocus sequence typing (MLST). All 12 isolates that belonged to the
      gentamicin-resistant group of MRSA were susceptible to vancomycin, but showed
      reduced susceptibility to teicoplanin through at least one MIC method. PFGE
      typing yielded five different but closely related profiles, and eight of the 12
      clinical isolates were classified into a single PFGE type. MLST yielded an
      identical allelic profile for all 12 isolates, corresponding to the profile (3-3
      1-12-4-4-16) of the 'Iberian' clone HPV107 of MRSA. MLST allowed us to confirm
      the presence of the 'Iberian' MRSA clone HPV107 with the same allelic profile in
      our hospital for several years. We can now note that strains of this clone have
      acquired reduced susceptibility to teicoplanin.

PMID- 12205057
TI  - Sequence and genome context analysis of a new molecular class D beta-lactamase
      gene from Legionella pneumophila.
AB  - Legionella pneumophila Philadelphia-1 (ATCC 33152) produces a serine active site
      beta-lactamase. The chromosomal gene that encodes this enzyme, loxA, has been
      cloned by PCR using information from the L. pneumophila Philadelphia-1 genome
      sequencing project. LoxA is a class 2d penicillinase, and its sequence puts it
      into the molecular class D beta-lactamase family, although phylogenetic analysis
      shows that LoxA forms a distinct branch in the OXA family along with the LoxA
      homologue, OXA-29, from Legionella gormanii ATCC 33297(T). Upstream of loxA on
      the L. pneumophila Philadelphia-1 chromosome is a two-gene locus similar to that
      found linked to the beta-lactamase genes of Gram-positive bacteria. The unit
      consists of loxI, encoding a homologue of the Gram-positive beta-lactamase
      expression regulator, and pbpX, encoding a putative penicillin-binding
      transpeptidase. Despite the presence of beta-lactamase regulator homologues, we
      could find no evidence of LoxA induction upon challenge of L. pneumophila
      Philadelphia-1 with beta-lactams.

PMID- 12205058
TI  - Analysis of the cytotoxicity of synthetic antimicrobial peptides on mouse
      leucocytes: implications for systemic use.
AB  - We have analysed the toxicity of highly cationic, artificial alpha-helical
      antimicrobial peptides on blood cells to assess their suitability for systemic
      application. Flow cytometric methods, based on the uptake of propidium iodide,
      were used to obtain a rapid and quantitative estimate of membrane damage to
      resting and concanavalin A-activated mouse lymphocytes, which was further
      confirmed by morphological changes as observed by scanning electron microscopy.
      Membrane permeabilization appeared to correlate with structural characteristics,
      so that the peptide L-19(9/B), which contains helix-stabilizing aminoisobutyric
      acid (Aib) residues and is a potent antimicrobial, was also the most lytic
      towards both mouse lymphocytes and human erythrocytes. Reducing the propensity
      for helix formation in P19(8) resulted in a marked reduction in in vitro
      cytotoxicity. Changing the helical sense in D-P19(9/B) also resulted in a
      significant decrease in cytolytic activity towards both erythrocytes and
      leucocytes. A limited assessment in BALB/c mice confirmed a lower in vivo
      toxicity of P19(8) than L-P19(9/B). In a study of the systemic antimycotic
      activity of P19(8) in a mouse protection model, a modest prolongation in survival
      of Candida albicans-infected animals after intravenous administration was
      observed at 5 mg/kg peptide but not at higher doses. The implications of these
      observations for the systemic use of this type of peptide are discussed.

PMID- 12205059
TI  - Efficacy and pharmacodynamics of simulated human-like treatment with levofloxacin
      on experimental pneumonia induced with penicillin-resistant pneumococci with
      various susceptibilities to fluoroquinolones.
AB  - Newer fluoroquinolones, such as levofloxacin, have shown an enhanced in vitro and
      in vivo activity against penicillin-resistant Streptococcus pneumoniae
      infections. The frequency of S. pneumoniae with reduced susceptibility to
      quinolones, although currently low, raises the question of the therapeutic
      efficacy of levofloxacin on infection due to such strains. We used an animal
      model of penicillin-resistant pneumococcal pneumonia using six strains with
      various levels of susceptibility to ciprofloxacin and levofloxacin in rabbits to
      induce pneumonia, and simulated a human-like treatment of 500 mg twice a day for
      48 h. Strains' susceptibility profiles for ciprofloxacin and levofloxaxin were
      (ciprofloxacin/levofloxacin MIC, mg/L; genotype): 0.5/0.5 (Cip0.5), 2/1 (Cip2),
      4/1.75 (Cip4), 8/1.75 (parC mutation) (Cip8), 10/2 (parC mutation) (Cip10), 64/16
      (parC and gyrA mutations) (Cip64), respectively. All the strains induced a crude
      pneumonia in all rabbits. Significant bacterial reductions at the end of
      treatment in lung and spleen were observed for the four former strains (P < 0.05)
      but not for the latter two. An AUC/MIC ratio of at least 32 identified 95% of an
      at least bacteriostatic effect (P = 0.038) and 76% of a bactericidal effect (P =
      0.09). Mutants were detected in treated animals infected with strains harbouring
      parC mutations (Cip8 and Cip10) and when the AUC/MIC ratio was between 13 and 31.
      We conclude that levofloxacin is effective against experimental pneumonia due to
      pneumococci with MIC < 1.5 mg/L, ineffective on experimental pneumonia due to
      pneumococci with MIC > or = 2 mg/L, and could be associated with the appearance
      of mutants when a parC mutation is pre-existing.

PMID- 12205060
TI  - Zeamatin, clotrimazole and nikkomycin Z in therapy of a Candida vaginitis model.
AB  - OBJECTIVE: To study the interaction of antifungal drugs in topical therapy.
      MATERIALS AND METHODS: Local therapy of Candida vaginitis with drugs alone and in
      combination was examined in a murine model. Zeamatin, a natural plant-derived
      antifungal protein, was tested alone and in combination with an azole,
      clotrimazole or nikkomycin Z, a chitin synthase inhibitor. RESULTS: Whereas
      alone, zeamatin was ineffective, nikkomycin Z was effective only when dosed
      multiple times per day, and clotrimazole efficacy was variable when administered
      in experimental vehicles (unlike the complex and undefined commercial
      preparation), zeamatin enhanced the efficacy of either of the other two drugs
      when they were given in combination. CONCLUSION: Drug interactions between novel
      drugs with unique mechanisms of action should be explored further, and may lead
      to more potent regimens.

PMID- 12205061
TI  - Pharmacokinetic and antiretroviral activity in mice of oral [P(1),P(2)-bis[2
      (adenin-9-yl)ethoxymethyl]phosphonate], a prodrug of 9-(2
      phosphonylmethoxyethyl)adenine.
AB  - 9-(2-Phosphonylmethoxyethyl)adenine (PMEA) is an antiviral drug with activity
      against herpes viruses, Epstein-Barr virus and retroviruses, including the human
      immunodeficiency virus. Unfortunately, oral PMEA administration, as required for
      long-term therapy, is hindered by its low bioavailability. In the present study,
      the synthesis, oral bioavailability and antiretroviral activity of a new prodrug
      of PMEA, consisting of two molecules of PMEA bound together by a P-O-P bond (Bis
      PMEA), are reported. Pharmacokinetic experiments in mice showed that the oral
      bioavailabilities of PMEA following oral gavage of Bis-PMEA or PMEA (at a dose
      equivalent to 28 mg of PMEA/kg) were 50.8 and 13.5%, respectively. These results
      correlate with the antiviral efficacy of Bis-PMEA administered orally at a dose
      equivalent to 50 mg/kg of PMEA in C57 BL/6 mice infected with the retroviral
      complex LP-BM5. Oral treatment with Bis-PMEA proved to be more effective than
      oral treatment with PMEA given at equimolar doses. Moreover, oral Bis-PMEA was
      more effective than intraperitoneal PMEA (50 mg/kg) in reducing lymphoadenopathy,
      hypergammaglobulinaemia and lymph node proviral DNA content, overall in the first
      weeks post virus inoculation. Bis-PMEA thus appears to be an efficient oral
      prodrug of PMEA without significant toxicity, at least in this mouse model.

PMID- 12205062
TI  - Risk factors and predictors of mortality of methicillin-resistant Staphylococcus
      aureus (MRSA) bacteraemia in HIV-infected patients.
AB  - OBJECTIVES: To define the incidence, risk factors and short-term predictors of
      mortality of methicillin-resistant Staphylococcus aureus (MRSA) bacteraemia in
      HIV-infected patients. PATIENTS AND METHODS: All HIV-infected subjects with S.
      aureus bacteraemia were consecutively enrolled in a case-control study between
      January 1, 1991 and December 31, 2000 and prospectively followed up. RESULTS: In
      the study period, 129 of 419 (31%) HIV-infected patients with bacteraemia had a
      diagnosis of S. aureus bacteraemia. The comparative analysis of incidence of S.
      aureus bacteraemia in the period 1991-96 and 1997-2000 showed a significant
      decrease (P < 0.001). The same trend was observed for MRSA bacteraemia (P =
      0.002). The analysis of antimicrobial resistance showed that among 129 S. aureus
      strains, 88 (68%) were methicillin susceptible and 41 (32%) were methicillin
      resistant. The majority of MRSA bacteraemia was hospital acquired (78%). Previous
      administration of beta-lactams (P < 0.001), multiple previous hospital admissions
      (P < 0.001) and low numbers of CD4+ peripheral cells (P < 0.001) were found to be
      independent risk factors of methicillin resistance at multivariate analysis. The
      mortality rate was 34% in the cases and 11% in the controls (P = 0.002).
      Multivariate analysis indicated that a high Acute Physiology and Chronic Health
      Evaluation (APACHE) III score (P < 0.001) and high HIV viraemia (P = 0.02), but
      not methicillin resistance, predicted an increased risk of death in patients with
      S. aureus bacteraemia. CONCLUSION: Individual exposure to beta-lactams, in
      association with a history of multiple hospitalizations and low CD4+ cell number,
      plays a pivotal role as a risk factor for the development of methicillin
      resistance in HIV-infected patients. Methicillin resistance does not influence
      the outcome of S. aureus bacteraemia when included in a multivariate analysis.

PMID- 12205063
TI  - Emergence of vancomycin-intermediate Staphylococcus aureus in a Belgian hospital:
      microbiological and clinical features.
AB  - In 1999, all clinical Staphylococcus aureus isolates from patients admitted to a
      Belgian University hospital were tested for decreased vancomycin susceptibility.
      Three vancomycin-intermediate Staphylococcus aureus (VISA) and four hetero-VISA
      strains were detected among 2145 isolates tested. They emerged from strains that
      belonged to locally endemic methicillin-resistant S. aureus (MRSA) genotypes in
      three patients who had received repeated courses of vancomycin therapy. A cystic
      fibrosis patient with MRSA/VISA-associated broncho-pulmonary exacerbation was
      successfully treated by continuous vancomycin infusion plus fusidic acid followed
      by oral minocycline-fusidic acid. Two other patients had VISA recovered from
      specimens of undetermined clinical significance. Emergence of VISA variants of
      endemic MRSA strains in Belgium warrants active microbiological surveillance and
      careful monitoring of vancomycin therapy. Therapy with high-dose vancomycin
      administered by continuous infusion in combination with other antimicrobials may
      be a therapeutic option worth investigating for VISA infection.

PMID- 12205064
TI  - Ceftazidime-hydrolysing CTX-M-15 extended-spectrum beta-lactamase (ESBL) in
      Poland.
AB  - The CTX-M-15 extended-spectrum beta-lactamase (ESBL) was recently identified in
      Enterobacteriaceae isolates in India, and demonstrated significant hydrolytic
      activity against ceftazidime, in contrast to the majority of CTX-M enzymes. CTX-M
      15 differs from CTX-M-3, which is one of the most prevalent ESBLs in Poland, by
      only a single amino acid change (Asp-240-->Gly). Three cefotaxime- and
      ceftazidime-resistant Enterobacteriaceae isolates, recovered during 1998-2000 in
      two Polish hospitals, were found to produce CTX-M-15. Similar to those from
      India, the isolates contained the ISEcp1 insertion sequence located upstream of
      the bla(CTX-M-15) gene, which has been recently demonstrated to mobilize 3'
      adjacent genes to transfer between DNA replicons. However, its different position
      with respect to the beta-lactamase gene indicated the independent selection of
      the ESBL gene in the two countries.

PMID- 12205065
TI  - First outbreak of vancomycin-resistant enterococci in a tertiary hospital in
      Turkey.
AB  - Twenty multidrug-resistant vancomycin-resistant Enterococcus faecium strains of
      the VanA phenotype were isolated over a 1 year period from five patients in the
      intensive care unit at the University Hospital of Antalya, Turkey. Molecular
      investigation showed that these strains belonged to five different pulsotypes and
      that the vanA gene was carried by a Tn1546-like transposon inserted onto a self
      transferable plasmid of approximately 200 kb. One patient was infected by two
      different strains, suggesting horizontal gene transfer within that patient. This
      is the first documented outbreak of VRE in Turkey with concomitant spread of
      plasmid and strains.

PMID- 12205066
TI  - Genotypic characterization of macrolide-resistant strains of Streptococcus
      pneumoniae isolated in Quebec, Canada, and in vitro activity of ABT-773 and
      telithromycin.
AB  - Increasing resistance of Streptococcus pneumoniae to macrolides represents a
      challenge for clinicians. New ketolides have an enhanced activity against
      macrolide-resistant strains. Four hundred and seventy-four strains of S.
      pneumoniae were collected during the 2000-2001 season in Quebec through a
      surveillance network. Macrolide resistance was 20.2%, and significantly higher in
      non-invasive strains versus invasive ones (22.4% versus 14.8%), and in children
      (30%) versus adults (14.8%). For susceptible strains, MIC(90)s of ABT-773 and
      telithromycin were 0.008 and 0.015 mg/L. Among the 96 macrolide-resistant
      strains, 56 (58%) were erm(B), 35 (37%) carried the mef(A) gene, four were
      carrying both genes and one none. ABT-773 and telithromycin were very active
      against all these resistant strains irrespective of the resistance mechanism,
      with MIC(90)s of 0.25 and 0.5 mg/L, respectively.

PMID- 12205067
TI  - Comparative in vitro activity of garenoxacin against Chlamydia spp.
AB  - The in vitro susceptibilities of 33 isolates of Chlamydia trachomatis, Chlamydia
      pneumoniae and Chlamydia psittaci to a new quinolone drug, garenoxacin (BMS
      284756), in comparison with levofloxacin, ciprofloxacin, doxycycline,
      erythromycin and roxithromycin, were determined. Garenoxacin was the most active
      of the quinolone drugs tested, with identical MIC and MBC, which ranged from
      0.007 to 0.03 mg/L. The MIC and MBC of the other two quinolones tested,
      levofloxacin and ciprofloxacin, were also identical, ranging from 0.25 to 2 mg/L.
      The MICs and MBCs of doxycycline, erythromycin and roxithromycin were also
      determined.

PMID- 12205068
TI  - Comparative in vitro activity of faropenem and 11 other antimicrobial agents
      against 405 aerobic and anaerobic pathogens isolated from skin and soft tissue
      infections from animal and human bites.
AB  - Faropenem, a new oral beta-lactam agent with a penem structure, was very active
      against 405 aerobic and anaerobic bite isolates. It inhibited 232 of 236 (98%)
      aerobic isolates, including all Pasteurella spp. and Eikenella corrodens at < or
      = 0.25 mg/L, and 164/169 (97%) anaerobic isolates, at < or = 1 mg/L. The 10
      isolates that required > or = 2 mg/L for inhibition were one strain each of
      Acinetobacter lwoffi, Corynebacterium minutissimum, Bacteroides ovatus,
      Lactobacillus delbrueckii and Peptostreptococcus tetradius, plus Corynebacterium
      'aquaticum' (two strains) and Veillonella sp. (three strains).

PMID- 12205069
TI  - Significance of low-level resistance to ciprofloxacin in Klebsiella pneumoniae
      and the effect of increased dosage of ciprofloxacin in vivo using the rat
      granuloma pouch model.
AB  - This study was designed to compare the killing effect of ciprofloxacin on strains
      of Klebsiella pneumoniae with different MICs of ciprofloxacin in vivo using the
      rat granuloma pouch infection model. Five different strains were used: one
      ciprofloxacin-susceptible strain (MIC 0.06 mg/L); one strain highly resistant to
      ciprofloxacin (MIC 8 mg/L); and three nalidixic acid-resistant strains with low
      level resistance to ciprofloxacin (MIC 0.25-0.5 mg/L). The efficacy of
      ciprofloxacin was evaluated 3 h after bacterial challenge (treating an acute
      infection) or after 3 days (treating a late infection) with a single
      intraperitoneal injection of ciprofloxacin (40 and 200 mg/kg). Ciprofloxacin was
      bactericidal against both growing K. pneumoniae (acute infection model) and non
      growing K. pneumoniae (late infection model), but the extent of killing was
      significantly higher on growing bacteria and against ciprofloxacin-susceptible K.
      pneumoniae. A peak concentration of ciprofloxacin, at the infection site, <3 x
      MIC was not sufficient for optimal bacterial elimination. However, it was
      possible to compensate for the lower killing in low-level ciprofloxacin-resistant
      K. pneumoniae by increasing the dosage of ciprofloxacin from 40 to 200 mg/kg,
      consistent with the higher MIC.

PMID- 12205070
TI  - Pharmacodynamics of cefepime in patients with Gram-negative infections.
AB  - We conducted a prospective, open-label study to delineate a relationship between
      exposure and outcomes in 36 patients treated with cefepime. Twenty patients had
      documented Gram-negative infections. Timed blood and urine samples were obtained
      at steady state to determine pharmacokinetic and pharmacodynamic parameters.
      Microbiological success was significantly correlated with the proportion of the
      dosing interval that cefepime concentrations exceeded 4.3 x MIC. Our results
      support in vitro data that suggest bactericidal activity of beta-lactams is
      optimized at concentrations approximately 4 x MIC. These results should be
      validated by large prospective clinical trials.

PMID- 12205071
TI  - Free and total cefazolin plasma and interstitial fluid concentrations at steady
      state during continuous infusion.
AB  - Free and total concentrations of cefazolin were compared in plasma and
      interstitial fluid during continuous intravenous infusion therapy. Seven
      patients, median age 53 (25-74) years, were administered a constant infusion of
      cefazolin at a mean (+/-S.D.) dose of 3.5 g (+/-1.1) per 24 h for > or = 5 days.
      Four blisters were induced on the forearm of each patient for sampling of
      interstitial fluid. Free concentrations in plasma and interstitial fluid were
      similar, and correlated better than total concentrations (r(2) = 0.82, P = 0.005
      versus r(2) = 0.54, P = 0.056). In all patients, the free concentrations in the
      interstitial fluid were at least two-fold the MIC(90) for Staphylococcus aureus.

PMID- 12205072
TI  - Azithromycin is effective in patients with chronic bronchitis.

PMID- 12205073
TI  - Reply to: Ciprofloxacin susceptibility testing of enterococcal urinary isolates
      in accordance with BSAC guidelines.

PMID- 12205075
TI  - Ganciclovir treatment of symptomatic congenital cytomegalovirus infection.

PMID- 12205076
TI  - Prevalence of macrolide and tetracycline resistance mechanisms in Streptococcus
      pyogenes isolates and in vitro susceptibility to telithromycin.

PMID- 12205078
TI  - Evidence of cross-resistance between ciprofloxacin and non-fluoroquinolones in
      European Gram-negative clinical isolates.

PMID- 12205079
TI  - Time-dependent antibacterial effects of linezolid in experimental rabbit
      endocarditis.

PMID- 12205080
TI  - Coenzymatic activity of randomly broken or intact double-stranded DNAs in auto
      and histone H1 trans-poly(ADP-ribosylation), catalyzed by poly(ADP-ribose)
      polymerase (PARP I).
AB  - The enzymatic transfer of ADP-ribose from NAD to histone H1 (defined as trans
      poly(ADP-ribosylation)) or to PARP I (defined as auto-poly(ADP-ribosylation)) was
      studied with respect to the nature of the DNA required as a coenzyme. Linear
      double-stranded DNA (dsDNA) containing the MCAT core motif was compared with DNA
      containing random nicks (discontinuous or dcDNA). The dsDNAs activated trans
      poly(ADP-ribosylation) about 5 times more effectively than dcDNA as measured by
      V(max). Activation of auto-poly(ADP-ribosylation) by dcDNA was 10 times greater
      than by dsDNA. The affinity of PARP I toward dcDNA or dsDNA in the auto-poly(ADP
      ribosylation) was at least 100-fold lower than in trans-poly(ADP-ribosylation)
      (K(a) = 1400 versus 3-15, respectively). Mg2+ inhibited trans-poly(ADP
      ribosylation) and so did dcDNA at concentrations required to maximally activate
      auto-poly(ADP-ribosylation). Mg2+ activated auto-poly(ADP-ribosylation) of PARP
      I. These results for the first time demonstrate that physiologically occurring
      dsDNAs can serve as coenzymes for PARP I and catalyze preferentially trans
      poly(ADP- ribosylation), thereby opening the possibility to study the physiologic
      function of PARP I.

PMID- 12205081
TI  - Crystal structure of the anticoagulant slow form of thrombin.
AB  - Using the thrombin mutant R77aA devoid of the site of autoproteolytic degradation
      at exosite I, we have solved for the first time the structure of thrombin free of
      any inhibitors and effector molecules and stabilized in the Na(+)-free slow form.
      The slow form shows subtle differences compared with the currently available
      structures of the Na(+)-bound fast form that carry inhibitors at the active site
      or exosite I. The most notable differences are the displacement of Asp-189 in the
      S1 specificity pocket, a downward shift of the 190-193 strand, a rearrangement of
      the side chain of Glu-192, and a significant shift in the position of the
      catalytic Ser-195 that is no longer within H-bonding distance from His-57. The
      structure of the slow form explains the reduced specificity toward synthetic and
      natural substrates and suggests a molecular basis for its anticoagulant
      properties.

PMID- 12205082
TI  - Impaired trafficking of connexins in androgen-independent human prostate cancer
      cell lines and its mitigation by alpha-catenin.
AB  - Gap junctions, composed of connexins, provide a pathway of direct intercellular
      communication for the diffusion of small molecules between cells. Evidence
      suggests that connexins act as tumor suppressors. We showed previously that
      expression of connexin-43 and connexin-32 in an indolent prostate cancer cell
      line, LNCaP, resulted in gap junction formation and growth inhibition. To
      elucidate the role of connexins in the progression of prostate cancer from a
      hormone-dependent to -independent state, we introduced connexin-43 and connexin
      32 into an invasive, androgen-independent cell line, PC-3. Expression of these
      proteins in PC-3 cells resulted in intracellular accumulation. Western blot
      analysis revealed a lack of Triton-insoluble, plaque-assembled connexins. In
      contrast to LNCaP cells, connexins could not be cell surface-biotinylated and did
      not reside in the cell surface derived endocytic vesicles, in PC-3 cells,
      suggesting impaired trafficking to the cell surface. Intracellular accumulation
      of connexins was observed in several androgen-independent prostate cancer cell
      lines. Transient expression of alpha-catenin facilitated the trafficking of both
      connexins to the cell surface and induced gap junction assembly. Our results
      suggest that impaired trafficking, and not the inability to form gap junctions,
      is the major cause of communication deficiency in human prostate cancer cell
      lines.

PMID- 12205083
TI  - Relevance of dopamine signals anchoring dynamin-2 to the plasma membrane during
      Na+,K+-ATPase endocytosis.
AB  - Clathrin-dependent endocytosis of Na(+),K(+)-ATPase in response to dopamine
      regulates its catalytic activity in intact cells. Because fission of clathrin
      coated pits requires dynamin, we examined the mechanisms by which dopamine
      receptor signals promote dynamin-2 recruitment and assembly at the site of
      Na(+),K(+)-ATPase endocytosis. Western blotting revealed that dopamine increased
      the association of dynamin-2 with the plasma membrane and with
      phosphatidylinositol 3-kinase. Dopamine inhibited Na(+),K(+)-ATPase activity in
      OK cells and in those overexpressing wild type dynamin-2 but not in cells
      expressing a dominant-negative mutant. Dephosphorylation of dynamin is important
      for its assembly. Dopamine increased protein phosphatase 2A activity and
      dephosphorylated dynamin-2. In cells expressing a dominant-negative mutant of
      protein phosphatase 2A, dopamine failed to dephosphorylate dynamin-2 and to
      reduce Na(+),K(+)-ATPase activity. Dynamin-2 is phosphorylated at Ser(848), and
      expression of the S848A mutant significantly blocked the inhibitory effect of
      dopamine. These results demonstrate a distinct signaling network originating from
      the dopamine receptor that regulates the state of dynamin-2 phosphorylation and
      that promotes its location (by interaction with phosphatidylinositol 3-kinase) at
      the site of Na(+),K(+)-ATPase endocytosis.

PMID- 12205084
TI  - Identification of a conserved GATA3 response element upstream proximal from the
      interleukin-13 gene locus.
AB  - Differentiation of naive CD4 T cells into type 2 helper (Th2) cells is
      accompanied by chromatin remodeling of Th2 cytokine gene loci. Hyperacetylation
      of histone H3 on nucleosomes associated with the interleukin (IL)-4, IL-13 and IL
      5 genes was observed in developing Th2 cells but not in Th1 cells. Histone
      hyperacetylation on IL-5 gene-associated nucleosomes was Th2-specific but
      occurred with delayed kinetics, and hyperacetylation on RAD50 gene-associated
      nucleosomes was T cell antigen receptor stimulation-dependent but not Th2
      specific. The induction of the Th2-specific histone hyperacetylation was STAT6-
      and GATA3-dependent, and interestingly, it was accompanied by the expression of
      intergenic transcripts within the IL-13 and IL-4 gene loci. A conserved GATA3
      response element (CGRE) containing four GATA consensus sequences was identified
      1.6 kbp upstream from the IL-13 gene, corresponding with the 5'-border of the Th2
      specific histone hyperacetylation region. The CGRE was shown to bind to GATA3,
      histone acetyltransferase complexes including CBP/p300, and RNA polymerase II.
      Also, the CGRE showed a significant enhancing effect on the Th2 cytokine gene
      promoters. Thus, the CGRE may play a crucial role for GATA3-mediated targeting
      and downstream spreading of core histone hyperacetylation within the IL-13 and IL
      4 gene loci.

PMID- 12205085
TI  - Trigger factor retards protein export in Escherichia coli.
AB  - Trigger factor (TF) is a ribosome-associated protein that interacts with a wide
      variety of nascent polypeptides in Escherichia coli. Previous studies have
      indicated that TF cooperates with DnaK to facilitate protein folding, but the
      basis of this cooperation is unclear. In this study we monitored protein export
      in E. coli that lack or overproduce TF to obtain further insights into its
      function. Whereas inactivation of genes encoding most molecular chaperones
      (including dnaK) impairs protein export, inactivation of the TF gene accelerated
      protein export and suppressed the need for targeting factors to maintain the
      translocation competence of presecretory proteins. Furthermore, overproduction of
      TF (but not DnaK) markedly retarded protein export. Manipulation of TF levels
      produced similar effects on the export of a cytosolic enzyme fused to a signal
      peptide. The data strongly suggest that TF has a unique ability to sequester
      nascent polypeptides for a relatively prolonged period. Based on our results, we
      propose that TF and DnaK promote protein folding by distinct (but complementary)
      mechanisms.

PMID- 12205086
TI  - Abrogation of upstream open reading frame-mediated translational control of a
      plant S-adenosylmethionine decarboxylase results in polyamine disruption and
      growth perturbations.
AB  - S-Adenosylmethionine decarboxylase (AdoMetDC) is a key enzyme in polyamine
      biosynthesis. We show that the plant AdoMetDC activity is subject to post
      transcriptional control by polyamines. A highly conserved small upstream open
      reading frame (uORF) in the AdoMetDC mRNA 5' leader is responsible for
      translational repression of a downstream beta-glucuronidase reporter cistron in
      transgenic tobacco plants. Elimination of the small uORF from an AdoMetDC cDNA
      led to increased relative translational efficiency of the AdoMetDC proenzyme in
      transgenic plants. The resulting increased activity of AdoMetDC caused disruption
      to polyamine levels with depletion of putrescine, reduction of spermine levels,
      and a more than 400-fold increase in the level of decarboxylated S
      adenosylmethionine. These changes were associated with severe growth and
      developmental defects. The high level of decarboxylated S-adenosylmethionine was
      not associated with any change in 5'-methylcytosine content in genomic DNA and S
      adenosylmethionine levels were more or less normal, indicating a highly efficient
      system for maintenance of S-adenosylmethionine levels in plants. This work
      demonstrates that uORF-mediated translational control of AdoMetDC is essential
      for polyamine homeostasis and for normal growth and development.

PMID- 12205087
TI  - Squash glycerol-3-phosphate (1)-acyltransferase. Alteration of substrate
      selectivity and identification of arginine and lysine residues important in
      catalytic activity.
AB  - Glycerol-3-phosphate 1-acyltransferase is a soluble chloroplast enzyme involved
      in glycerol-lipid biosynthesis associated with chilling resistance in plants ().
      Resistance is associated with higher selectivity for unsaturated acyl substrates
      over saturated ones. In vitro substrate selectivity assays performed under
      physiologically relevant conditions have been established that discriminate
      between selective and non-selective forms of the enzyme. A mutation, L261F, in
      the squash protein converts it from a non-selective enzyme into a selective one.
      The mutation lies within 10 A of the predicted acyl binding site and results in a
      higher K(m) for 16:0 acyl carrier protein (ACP). Site-directed mutagenesis was
      used to determine the importance of four residues, Arg(235), Arg(237), Lys(193),
      and His(194), implicated to be involved in binding of the phosphate group of
      glycerol 3-phosphate to the enzyme. All the proteins were highly homologous in
      structure to the wild type enzyme. Mutations in Arg(235), Arg(237), and Lys(193)
      resulted in inactive enzyme, while His(194) had reduced catalytic activity. The
      mutant proteins retained the ability to bind stoichiometric quantities of acyl
      ACPs supporting the potential role of these residues in glycerol 3-phosphate
      binding.

PMID- 12205088
TI  - RAG2 is down-regulated by cytoplasmic sequestration and ubiquitin-dependent
      degradation.
AB  - Periodic accumulation and degradation of RAG2 (recombination-activating gene 2)
      protein controls the cell-cycle-dependent V(D)J recombination of lymphocyte
      antigen receptor genes. Here we show the molecular mechanism of RAG2 degradation.
      The RAG2 protein is translocated from the nucleus to the cytoplasm and degraded
      through the ubiquitin/proteasome system. RAG2 translocation is mediated by the
      Thr-490 phosphorylation of RAG2. Inhibition of this phosphorylation by p27Kip1
      stabilizes the RAG2 protein in the nucleus. These results suggest that RAG2
      sequestration in the cytoplasm and its subsequent degradation by the
      ubiquitin/proteasome system upon entering the S phase is an integral part of
      G0/G1-specific V(D)J recombination.

PMID- 12205089
TI  - Clathrin-mediated endocytosis and recycling of the neuron-specific Na+/H+
      exchanger NHE5 isoform. Regulation by phosphatidylinositol 3'-kinase and the
      actin cytoskeleton.
AB  - Mammalian Na+/H+ exchangers (NHEs) are a family of integral membrane proteins
      that play central roles in sodium, acid-base, and cell volume homeostasis. The
      recently cloned NHE5 isoform is expressed predominantly in brain, but its
      functional and cellular properties are poorly understood. To facilitate its
      characterization, an epitope-tagged construct of NHE5 was ectopically expressed
      in nonneuronal and neuronal cells. In NHE-deficient Chinese hamster ovary AP-1
      cells, NHE5 localized at the plasmalemma, but a significant fraction accumulated
      intracellularly in vesicles that concentrated in a juxtanuclear region.
      Similarly, in nerve growth factor-differentiated neuroendocrine PC12 cells and
      primary hippocampal neurons, immunolabeling of NHE5 was detected in endomembrane
      vesicles in the perinuclear region of the cell body but also along the processes.
      More detailed characterization in AP-1 cells using organelle-specific markers
      showed that NHE5 co-localized with internalized transferrin, a marker of
      recycling endosomes. Transient transfection of a dominant negative mutant of
      dynamin-1, which inhibits clathrin-mediated endocytosis, blocked uptake of
      transferrin as well as internalization of NHE5. Likewise, wortmannin inhibition
      of phosphatidylinositol 3'-kinase, a lipid kinase implicated in endosomal
      traffic, induced coalescence of vesicles containing NHE5 and caused a pronounced
      inhibition of plasmalemmal Na+/H+ exchange. By contrast, disruption of the F
      actin cytoskeleton with cytochalasin D increased cell surface NHE5 activity and
      abundance. These observations demonstrate that NHE5 is localized to the recycling
      endosomal pathway and is dynamically regulated by phosphatidylinositol 3'-kinase
      and by the state of F-actin assembly.

PMID- 12205090
TI  - Two highly conserved glutamate residues critical for type III sodium-dependent
      phosphate transport revealed by uncoupling transport function from retroviral
      receptor function.
AB  - Type III sodium-dependent phosphate (NaP(i)) cotransporters, Pit1 and Pit2, have
      been assigned housekeeping P(i) transport functions and suggested involved in
      chondroblastic and osteoblastic mineralization and ectopic calcification. Both
      proteins exhibit dual function, thus, besides being transporters, they also serve
      as receptors for several gammaretroviruses. We here show that it is possible to
      uncouple transport and receptor functions of a type III NaP(i) cotransporter and
      thus exploit the retroviral receptor function as a control for proper processing
      and folding of mutant proteins. Thus exchanging two putative transmembranic
      glutamate residues in human Pit2, Glu(55) and Glu(575), with glutamine or with
      lysine severely impaired or knocked out, respectively, P(i) transport function,
      but left viral receptor function undisturbed. Both glutamates are conserved in
      type III NaP(i) cotransporters, in fungal NaP(i) cotransporters PHO-4 and Pho89,
      and in other known or putative phosphate permeases from a number of species and
      are the first residues shown to be critical for type III NaP(i) cotransport.
      Their putative transmembranic positions together with the presented data are
      consistent with Glu(55) and Glu(575) being parts of a cation liganding site or
      playing roles in conformational changes associated with substrate transport.
      Finally, the results also show that Pit2 retroviral receptor function per se is
      not dependent on Pit2 P(i) transport function.

PMID- 12205091
TI  - Leu-574 of HIF-1alpha is essential for the von Hippel-Lindau (VHL)-mediated
      degradation pathway.
AB  - Oxygen homeostasis is crucial for a myriad of developmental, physiological, and
      pathophysiological processes. Hypoxia-inducible factor 1alpha (HIF-1alpha) plays
      a pivotal role in response to hypoxia by transcriptionally activating target
      genes involving oxygen uptake, transport, delivery, and consumption. HIF-1alpha
      activity is regulated primarily through the ubiquitin-proteasome degradation
      pathway, which targets the oxygen-dependent degradation domain (ODD) of HIF
      1alpha. In particular, the von Hippel-Lindau (VHL) protein complex, an E3
      ubiquitin ligase, binds to the ODD upon hydroxylation of HIF-1alpha Pro-564.
      Here, we show that in vivo VHL interacts with the N-terminal as well as the C
      terminal ODD independently, supporting the notion of functional redundancy within
      the ODD. Moreover, we demonstrate that Leu-574 of HIF-1alpha is essential for VHL
      binding to the C-terminal ODD. Despite the presence of Pro-564, deletion or
      mutation of Leu-574 resulted in a loss of VHL binding and a gain of protein
      stability. Furthermore, the identification of Leu-574 redefines the N-terminal
      activation domain of HIF-1alpha to be constitutively active. Taken together, this
      study provides new insight into the mechanisms underlying VHL-mediated HIF-1alpha
      degradation and transcriptional activation, and a molecular basis for drug
      targeting.

PMID- 12205092
TI  - The third intracellular loop of alpha 2-adrenergic receptors determines subtype
      specificity of arrestin interaction.
AB  - Nonvisual arrestins (arrestin-2 and -3) serve as adaptors to link agonist
      activated G protein-coupled receptors to the endocytic machinery. Although many G
      protein-coupled receptors bind arrestins, the molecular determinants involved in
      binding remain largely unknown. Because arrestins selectively promote the
      internalization of the alpha(2b)- and alpha(2c)-adrenergic receptors (ARs) while
      having no effect on the alpha(2a)AR, here we used alpha(2)ARs to identify
      molecular determinants involved in arrestin binding. Initially, we assessed the
      ability of purified arrestins to bind glutathione S-transferase fusions
      containing the third intracellular loops of the alpha(2a)AR, alpha(2b)AR, or
      alpha(2c)AR. These studies revealed that arrestin-3 directly binds to the
      alpha(2b)AR and alpha(2c)AR but not the alpha(2a)AR, whereas arrestin-2 only
      binds to the alpha(2b)AR. Truncation mutagenesis of the alpha(2b)AR identified
      two arrestin-3 binding domains in the third intracellular loop, one at the N
      terminal end (residues 194-214) and the other at the C-terminal end (residues 344
      368). Site-directed mutagenesis further revealed a critical role for several
      basic residues in arrestin-3 binding to the alpha(2b)AR third intracellular loop.
      Mutation of these residues in the holo-alpha(2b)AR and subsequent expression in
      HEK 293 cells revealed that the mutations had no effect on the ability of the
      receptor to activate ERK1/2. However, agonist-promoted internalization of the
      mutant alpha(2b)AR was significantly attenuated as compared with wild type
      receptor. These results demonstrate that arrestin-3 binds to two discrete regions
      within the alpha(2b)AR third intracellular loop and that disruption of arrestin
      binding selectively abrogates agonist-promoted receptor internalization.

PMID- 12205093
TI  - Developmentally regulated N-terminal variants of the nuclear receptor hepatocyte
      nuclear factor 4alpha mediate multiple interactions through coactivator and
      corepressor-histone deacetylase complexes.
AB  - To understand the mechanisms governing the regulation of nuclear receptor (NR)
      function, we compared the parameters of activation and repression of two isoforms
      of the orphan receptor hepatocyte nuclear factor (HNF) 4alpha. HNF4alpha7 and
      HNF4alpha1 differ only in their N-terminal domains, and their expression in the
      liver is regulated developmentally. We show that the N-terminal activation
      function (AF)-1 of HNF4alpha1 possesses significant activity that can be enhanced
      through interaction with glucocorticoid receptor-interacting protein 1 (GRIP-1)
      and cAMP response element-binding protein-binding protein (CBP). In striking
      contrast, HNF4alpha7 possesses no measurable AF-1, implying major functional
      differences between the isoforms. Indeed, although HNF4alpha1 and HNF4alpha7 are
      able to interact via AF-2 with GRIP-1, p300, and silencing mediator for retinoid
      and thyroid receptors (SMRT), only HNF4alpha1 interacts in a synergistic fashion
      with GRIP-1 and p300. Although both isoforms interact physically and functionally
      with SMRT, the repression of HNF4alpha7 is less robust than that of HNF4alpha1,
      which may be caused by an increased ability of the latter to recruit histone
      deacetylase (HDAC) activity to target promoters. Moreover, association of SMRT
      with HDACs enhanced recruitment of HNF4alpha1 but not of HNF4alpha7. These
      observations suggest that NR isoform-specific association with SMRT could affect
      activity of the SMRT complex, implying that selection of HDAC partners is a novel
      point of regulation for NR activity. Possible physiological consequences of the
      multiple interactions with these coregulators are discussed.

PMID- 12205094
TI  - Cooperativity in transcription factor binding to the coactivator CREB-binding
      protein (CBP). The mixed lineage leukemia protein (MLL) activation domain binds
      to an allosteric site on the KIX domain.
AB  - The interactions between cAMP-response element-binding protein (CREB)-binding
      protein (CBP) and gene-specific transcription factors play an important role in
      activation of transcription from numerous genes. Cooperative interactions between
      CBP and multiple transcriptional activators may provide a mechanism for
      synergistic increases in transcriptional activation. Here we report the
      characterization of ternary complexes formed by the KIX domain of CBP and the
      transactivation domain of the trithorax group protein mixed lineage leukemia
      protein (MLL), together with either the phosphorylated kinase-inducible domain
      (pKID) of CREB or the activation domain from c-Myb. Isothermal titration
      calorimetry experiments show that KIX in complex with the MLL activation domain
      binds the c-Myb activation domain and pKID domain with 2-fold higher affinity
      than does the KIX domain alone. Thus, the activation domains of Myb and MLL or of
      pKID and MLL bind cooperatively to KIX. The thermodynamics of these interactions
      imply different mechanisms of binding cooperativity for the two ternary
      complexes; the KIX.MLL.pKID complex is stabilized by entropy increases, whereas
      the enhancement of Myb binding in the presence of the MLL activation domain is
      due to more favorable enthalpy. NMR experiments show that the MLL-binding site on
      KIX is distinct from the surface that binds the pKID and c-Myb activation
      domains. Our data indicate that KIX can directly mediate cooperative interactions
      between pairs of transcriptional regulatory proteins. In the case of MLL and c
      Myb, both proteins are involved in proliferation of hematopoietic cells and
      leukemogenesis, and synergistic interactions mediated by CBP may play a
      functional role.

PMID- 12205096
TI  - Crystal structure of ClpA, an Hsp100 chaperone and regulator of ClpAP protease.
AB  - Escherichia coli ClpA, an Hsp100/Clp chaperone and an integral component of the
      ATP-dependent ClpAP protease, participates in regulatory protein degradation and
      the dissolution and degradation of protein aggregates. The crystal structure of
      the ClpA subunit reveals an N-terminal domain with pseudo-twofold symmetry and
      two AAA(+) modules (D1 and D2) each consisting of a large and a small sub-domain
      with ADP bound in the sub-domain junction. The N-terminal domain interacts with
      the D1 domain in a manner similar to adaptor-binding domains of other AAA(+)
      proteins. D1 and D2 are connected head-to-tail consistent with a cooperative and
      vectorial translocation of protein substrates. In a planar hexamer model of ClpA,
      built by assembling ClpA D1 and D2 into homohexameric rings of known structures
      of AAA(+) modules, the differences in D1-D1 and D2-D2 interfaces correlate with
      their respective contributions to hexamer stability and ATPase activity.

PMID- 12205095
TI  - Targeted deletion of the Tsg101 gene results in cell cycle arrest at G1/S and p53
      independent cell death.
AB  - The tumor susceptibility gene 101 (Tsg101) was originally discovered in a screen
      for potential tumor suppressors using insertional mutagenesis in immortalized
      fibroblasts. To investigate essential functions of this gene in cell growth and
      neoplastic transformation, we derived primary mouse embryonic fibroblasts from
      Tsg101 conditional knockout mice. Expression of Cre recombinase from a retroviral
      vector efficiently down-regulated Tsg101. The deletion of Tsg101 caused growth
      arrest and cell death but did not result in increased proliferation and cellular
      transformation. Inactivation of p53 had no influence on the deleterious
      phenotype, but Tsg101(-/-) cells were rescued through expression of exogenous
      Tsg101. Fluorescence-activated cell sorting, proliferation assays, and Western
      blot analysis of crucial regulators of the cell cycle revealed that Tsg101
      deficiency resulted in growth arrest at the G(1)/S transition through
      inactivation of cyclin-dependent kinase 2. As a consequence, DNA replication was
      not initiated in Tsg101-deficient cells. Our results clearly demonstrate that
      Tsg101 is not a primary tumor suppressor in mouse embryonic fibroblasts. However,
      the protein is crucial for cell proliferation and cell survival.

PMID- 12205097
TI  - Structure and stability of an acidic fibroblast growth factor from Notophthalmus
      viridescens.
AB  - The three-dimensional solution structure of an acidic fibroblast growth factor
      (nFGF-1) from the newt (Notophthalmus viridescens) is determined using
      multidimensional NMR techniques. Complete assignment of all the atoms ((1)H,
      (15)N, and (13)C) has been achieved using a variety of triple resonance
      experiments. 50 structures were calculated using hybrid distance geometry
      dynamical simulated annealing technique with a total of 1359 constraints. The
      atomic root mean square distribution for the backbone atoms in the structured
      region is 0.60 A. The secondary structural elements include 12 beta-strands
      arranged antiparallely into a beta-barrel structure. The protein (nFGF-1) exists
      in a monomeric state upon binding to the ligand, sucrose octa sulfate (SOS), in a
      stoichiometric ratio of 1:1. The SOS binding site consists of a dense cluster of
      positively charged residues located at the C-terminal end of the molecule. The
      conformational stabilities of nFGF-1 and its structural and functional homologue
      from the human source (hFGF-1) are drastically different. The differential
      stabilities of nFGF-1 and hFGF-1 are attributed to the differences in the number
      of hydrogen bonds and the presence of solvent inaccessible cavities in the two
      proteins.

PMID- 12205098
TI  - Ligand receptor interactions in the Wnt signaling pathway in Drosophila.
AB  - Secreted Wnt proteins have numerous signaling functions during development,
      mediated by Frizzled molecules that act as Wnt receptors on the cell surface. In
      the genome of Drosophila, seven Wnt genes (including wingless; wg), and five
      frizzled genes have been identified. Relatively little is known about signaling
      and binding specificities of different Wnt and Frizzled proteins. We have
      developed an assay to determine the strength of binding between membrane-tethered
      Wnts and ligand binding domains of the Frizzled receptors. We found a wide
      spectrum of binding affinities, reflecting known genetic interactions. Most Wnt
      proteins can bind to multiple Frizzleds and vice versa, suggesting redundancy in
      vivo. In an extension of these experiments, we tested whether two different
      subdomains of the Wg protein would by themselves bind to Frizzled and generate a
      biological response. Whereas these two separate domains are secreted from cells,
      suggesting that they form independently folded parts of the protein, they were
      only able to evoke a response when co-transfected, indicating that both are
      required for function. In addition to the Frizzleds, members of the LRP family
      (represented by the arrow gene in Drosophila) are also necessary for Wnt signal
      transduction and have been postulated to act as co-receptors. We have therefore
      examined whether a soluble form of the Arrow molecule can bind to Wingless and
      Frizzled, but no interactions were detected.

PMID- 12205099
TI  - Identification and characterization of tyrosyl radical formation in Mycobacterium
      tuberculosis catalase-peroxidase (KatG).
AB  - The catalytic function of Mycobacterium tuberculosis catalase-peroxidase (KatG)
      and its role in activation of the anti-tuberculosis antibiotic isoniazid were
      investigated using rapid freeze-quench electron paramagnetic resonance (RFQ-EPR)
      experiments. The reaction of KatG with peroxyacetic acid was followed as a
      function of time using x-band EPR at 77 K. A doublet EPR signal appears within
      6.4 ms after mixing and at time points through hundreds of milliseconds.
      Thereafter, a singlet signal develops and finally predominates after 1 s, with a
      total yield of radical approximately 0.5 spin/heme. Simulation of the spectra
      provided EPR parameters consistent with those for tyrosyl radicals. Changes in
      the hyperfine splitting and/or line width in spectra for l-3,3-[2H2]tyrosine
      labeled, but not l-2,4,5,6,7-[2H5]tryptophan-labeled KatG confirmed this
      assignment. The initial rate of radical formation was unchanged using a 3-fold or
      10-fold excess of peroxyacetic acid, consistent with a rate-determining step
      involving an intermediate. Although Compound I is likely to be the precursor of
      tyrosyl radical in KatG, neither its EPR signal nor its reduction to Compound II
      during formation of the radical(s) could be observed. The tyrosyl radical doublet
      signal was rapidly quenched by addition of isoniazid and benzoic hydrazide, but
      not by iproniazid, which binds poorly to KatG.

PMID- 12205100
TI  - Homologous DNA pairing by human recombination factors Rad51 and Rad54.
AB  - Human Rad51 (hRad51) and Rad54 proteins are key members of the RAD52 group
      required for homologous recombination. We show an ability of hRad54 to promote
      transient separation of the strands in duplex DNA via its ATP hydrolysis-driven
      DNA supercoiling function. The ATPase, DNA supercoiling, and DNA strand opening
      activities of hRad54 are greatly stimulated through an interaction with hRad51.
      Importantly, we demonstrate that hRad51 and hRad54 functionally cooperate in the
      homologous DNA pairing reaction that forms recombination DNA intermediates. Our
      results should provide a biochemical model for dissecting the role of hRad51 and
      hRad54 in recombination reactions in human cells.

PMID- 12205101
TI  - Structure/function relationships responsible for the kinetic differences between
      human type 1 and type 2 3beta-hydroxysteroid dehydrogenase and for the catalysis
      of the type 1 activity.
AB  - Two distinct genes encode the 93% homologous type 1 (placenta, peripheral
      tissues) and type 2 (adrenals, gonads) 3beta-hydroxysteroid
      dehydrogenase/isomerase (3beta-HSD/isomerase) in humans. Mutagenesis studies
      using the type 1 enzyme have produced the Y154F and K158Q mutant enzymes in the
      Y(154)-P-H(156)-S-K(158) motif as well as the Y269S and K273Q mutants from a
      second motif, Y(269)-T-L-S-K(273), both of which are present in the primary
      structure of the human type 1 3beta-HSD/isomerase. In addition, the H156Y mutant
      of the type 1 enzyme has created a chimera of the type 2 enzyme motif (Y(154)-P
      Y(156)-S-K(158)) in the type 1 enzyme. The mutant and wild-type enzymes have been
      expressed and purified. The K(m) value of dehydroepiandrosterone is 13-fold
      greater, and the maximal turnover rate (K(cat)) is 2-fold greater for wild-type 2
      3beta-HSD compared with the wild-type 1 3beta-HSD activity. The H156Y mutant of
      the type 1 enzyme has substrate kinetic constants for 3beta-HSD activity that are
      very similar to those of the wild-type 2 enzyme. Dixon analysis shows that
      epostane inhibits the 3beta-HSD activity of the wild-type 1 enzyme with 14-17
      fold greater affinity compared with the wild-type 2 and H156Y enzymes. The Y154F
      and K158Q mutants exhibit no 3beta-HSD activity, have substantial isomerase
      activity, and utilize substrate with K(m) values similar to those of wild-type 1
      isomerase. The Y269S and K273Q mutants have low, pH-dependent 3beta-HSD activity,
      exhibit only 5% of the maximal isomerase activity, and utilize the isomerase
      substrate very poorly. From these studies, a structural basis for the profound
      differences in the substrate and inhibition kinetics of the wild-type 1 and 2
      3beta-HSD, plus a catalytic role for the Tyr(154) and Lys(158) residues in the
      3beta-HSD reaction have been identified. These advances in our understanding of
      the structure/function of human type 1 and 2 3beta-HSD/isomerase may lead to the
      design of selective inhibitors of the type 1 enzyme not only in placenta to
      control the onset of labor but also in hormone-sensitive breast, prostate, and
      choriocarcinoma tumors to slow their growth.

PMID- 12205102
TI  - Regulation of the uncoupling protein-2 gene in INS-1 beta-cells by oleic acid.
AB  - Current evidence suggests that uncoupling protein-2 (UCP2) is a regulator of
      insulin secretion. It is also known that chronic exposure of pancreatic islets to
      free fatty acids (FFAs) blunts glucose-stimulated insulin secretion and is
      accompanied by elevated levels of UCP2. However, the mechanisms regulating
      expression of UCP2 in beta-cells are unknown. Here, we show that UCP2 mRNA and
      protein levels were increased after a 48-h exposure of INS-1(832/13) beta-cells
      to oleic acid (0.5 mm) by activation of the UCP2 promoter. Furthermore,
      progressive deletions of the mouse UCP2 promoter (from -7.3 kb to +12 bp)
      indicated that an enhancer region (-86/-44) was responsible for both basal and
      FFA-stimulated UCP2 gene transcription. This enhancer contains tightly clustered
      Sp1, sterol regulatory element (SRE), and double E-Box elements. While all three
      sequence motifs were required for basal activity of the UCP2 promoter, the
      mutations in either the SRE or the E-Box elements eliminated the response to
      FFAs. The SRE and sterol regulatory element binding protein-1 (SREBP1) appear to
      be crucial for the response of the UCP2 gene to FFAs, since overexpression of the
      nuclear forms of the SREBPs increased UCP2 promoter activity by 7-10-fold and
      restored the ability of E-Box mutants to respond to oleic acid. These data
      support a model in which SREBP is the major modulator of UCP2 gene transcription
      by FFA, while E-Box binding factors play a supportive role.

PMID- 12205103
TI  - Hereditary paraganglioma targets diverse paraganglia.
AB  - Paragangliomas are highly vascularised and often heritable tumours derived from
      paraganglia, a diffuse neuroendocrine system dispersed from skull base to the
      pelvic floor. The carotid body, a small oxygen sensing organ located at the
      bifurcation of the carotid artery in the head and neck and the adrenal medulla in
      the abdomen, are the most common tumour sites. It now appears that mutations in
      SDHB, SDHC, and SDHD, which encode subunits of mitochondrial complex II
      (succinate dehydrogenase; succinate-ubiquinone oxidoreductase), are responsible
      for the majority of familial paragangliomas and also for a significant fraction
      of non-familial tumours. Germline mutations in complex II genes are associated
      with the development of paragangliomas in diverse anatomical locations, including
      phaeochromocytomas, a finding that has important implications for the clinical
      management of patients and genetic counselling of families. Consequently,
      patients with a paraganglioma tumour, including phaeochromocytoma, and a complex
      II germline mutation should be diagnosed with hereditary paraganglioma,
      regardless of family history, anatomical location, or multiplicity of tumours.
      This short review attempts to bring together relevant genetic data on
      paragangliomas with a particular emphasis on head and neck paragangliomas and
      phaeochromocytomas.

PMID- 12205104
TI  - Fraser syndrome and cryptophthalmos: review of the diagnostic criteria and
      evidence for phenotypic modules in complex malformation syndromes.
AB  - Fraser syndrome is characterised by cryptophthalmos, cutaneous syndactyly,
      malformations of the larynx and genitourinary tract, craniofacial dysmorphism,
      orofacial clefting, mental retardation, and musculoskeletal anomalies. The
      inheritance is autosomal recessive. No diagnostic cytogenetic abnormalities have
      been documented in affected patients, and no molecular genetic studies have been
      reported. We have reviewed 117 cases diagnosed as Fraser syndrome or
      cryptophthalmos published since the comprehensive review of Thomas et al in 1986
      in order to validate the published diagnostic criteria and to delineate the
      phenotype associated with this syndrome. Our series showed more females (57/117)
      than males and consanguinity was present in 29/119 (24.8%). Eighty-eight patients
      satisfied the diagnostic criteria for Fraser syndrome (75%). Cryptophthalmos was
      present in 103/117 (88%), syndactyly in 72/117 (61.5%), and ambiguous genitalia
      in 20/117 (17.1%). Ear malformations were recorded in 69/117 (59%), and renal
      agenesis in 53/117 (45.3%). Use of the published diagnostic criteria excluded
      several patients with cryptophthalmos and one or more physical feature(s)
      consistent with Fraser syndrome. The frequency of additional anomalies in our
      series was also higher than previously reported (for example, imperforate anus or
      anal stenosis were found in 34/117 (29%) compared with 2/124 (2%) in the series
      of Thomas et al (1986) and choanal stenosis or atresia was present in 7/117 (6%)
      compared to 0/124. These findings emphasise the clinical variability associated
      with Fraser syndrome and support genetic heterogeneity of the syndrome. We also
      noted patterns of anomalies (for example, bicornuate uterus with imperforate anus
      or anal stenosis and renal malformations) that are found in other syndromes and
      associations without cryptophthalmos, suggesting that common modifier genes may
      explain some of the phenotypic variation in Fraser syndrome.

PMID- 12205105
TI  - Identification of a locus for a form of spondyloepiphyseal dysplasia on
      chromosome 15q26.1: exclusion of aggrecan as a candidate gene.
AB  - We have investigated a family with an autosomal dominant form of
      spondyloepiphyseal dysplasia (SED) characterised by short stature and severe
      premature degenerative arthropathy. Previous studies have excluded linkage
      between this condition and the locus for the type II collagen gene. Here we
      report the identification of linkage between this disorder and a locus on the
      long arm of chromosome 15 between markers D15S979 and D15S1004. According to
      current linkage maps and sequence data, this locus includes that of the aggrecan
      gene (AGC1). Our linkage data from the SED family show, however, that AGC1 maps
      to a locus that is proximal to D15S979. This proximal location for AGC1 is
      further supported by linkage data from a second family with an autosomal
      recessive form of multiple epiphyseal dysplasia that also maps to the SED locus.
      In both families AGC1 is therefore excluded as a candidate gene.

PMID- 12205106
TI  - Apolipoprotein E4 is only a weak predictor of dementia and cognitive decline in
      the general population.
AB  - BACKGROUND: Apolipoprotein E (APOE) polymorphisms are unequivocally associated
      with risk for Alzheimer's disease (AD). It is crucial to understand how this
      genetic factor affects dementia risk in the general population, as well as in
      narrowly diagnosed, selected, patient groups. METHODS: We assessed the cross
      sectional association between APOE genotype and dementia status in a community
      based sample, the MRC Cognitive Function and Ageing Study (MRC CFAS). In
      addition, we tested the effects of APOE genotypes on the differences in MMSE
      scores between the first and third assessment waves (about six years apart), an
      index of cognitive decline. RESULTS: The APOE epsilon4 allele conferred increased
      risk for dementia (OR=1.5, 95% CI=1.1 to 2.2) compared to epsilon3 in the MRC
      CFAS sample. Compared with APOE epsilon3/epsilon 3 subjects, those with the
      epsilon3/epsilon4 genotypes were not at significantly higher risk for dementia
      (OR=1.1, 95% CI=0.6 to 1.9), although epsilon4/epsilon4 subjects were (OR= 3.8,
      95% CI=1.0 to 14.0). Risk estimates were not different between men and women.
      Notably, our risk estimates for dementia were significantly lower than those
      reported for a diagnosis of Alzheimer's disease. MMSE scores at wave 3 and the
      difference in MMSE between baseline and at the third assessment wave were not
      different across APOE genotypes. INTERPRETATION: The APOE epsilon4 allele is a
      weaker predictor for dementia in the general population than for AD. This may be
      because dementia can be caused by non-AD pathological processes and because most
      prevalent dementia occurs at an age when the APOE epsilon4 effect on AD risk (and
      therefore dementia) has started to decline.

PMID- 12205108
TI  - Mapping of a novel locus for achromatopsia (ACHM4) to 1p and identification of a
      germline mutation in the alpha subunit of cone transducin (GNAT2).
AB  - OBJECTIVE: To determine the molecular basis for achromatopsia using autozygosity
      mapping and positional candidate gene analysis. DESIGN AND METHODS: A large
      consanguineous Pakistani family containing six subjects with autosomal recessive
      complete achromatopsia was ascertained. After excluding linkage to the two known
      achromatopsia genes (CNGA3 and CNGB3), a genome wide linkage screen was
      undertaken. RESULTS: Significant linkage was detected to a 12 cM autozygous
      segment between markers D1S485 and D1S2881 on chromosome 1p13. Direct sequence
      analysis of the candidate gene GNAT2 located within this interval identified a
      frameshift mutation in exon 7 (c842_843insTCAG; M280fsX291) that segregated with
      the disease. CONCLUSIONS: The GNAT2 gene codes for cone alpha-transducin, the G
      protein that couples the cone pigments to cGMP-phosphodiesterase in
      phototransduction. Although cone alpha-transducin has a fundamental role in cone
      phototransduction, mutations in GNAT2 have not been described previously. Since
      mutations in the CNGA3 gene may cause a variety of retinal dystrophies (complete
      and incomplete achromatopsia and progressive cone dystrophy), GNAT2 mutations may
      also prove to be implicated in other forms of retinal dystrophy with cone
      dysfunction.

PMID- 12205107
TI  - Identification of candidate lung cancer susceptibility genes in mouse using
      oligonucleotide arrays.
AB  - We applied microarray gene expression profiling to lungs from mouse strains
      having variable susceptibility to lung tumour development as a means to identify,
      within known quantitative trait loci (QTLs), candidate genes responsible for
      susceptibility or resistance to lung cancer. At least eight chromosomal regions
      of mice have been mapped and verified to be linked with lung tumour
      susceptibility or resistance. In this study, high density oligonucleotide arrays
      were used to measure the relative expression levels of >36 000 genes and ESTs in
      lung tissues of A/J, BALB/cJ, SM/J, C3H/HeJ, and C57BL/6J mice. A number of
      differentially expressed genes were found in each of the lung cancer
      susceptibility QTLs. Bioinformatic analysis of the differentially expressed genes
      located within QTLs produced 28 susceptibility candidates and 22 resistance
      candidates. These candidates may be extremely helpful in the ultimate
      identification of the precise genes responsible for lung tumour susceptibility or
      resistance in mice and, through follow up, humans. Complete data sets are
      available at http://thinker.med.ohio-state.edu.

PMID- 12205110
TI  - Spondyloepimetaphyseal dysplasia with multiple dislocations (Hall type): three
      further cases and evidence of autosomal dominant inheritance.

PMID- 12205109
TI  - Vitreoretinopathy with phalangeal epiphyseal dysplasia, a type II collagenopathy
      resulting from a novel mutation in the C-propeptide region of the molecule.
AB  - A large family with dominantly inherited rhegmatogenous retinal detachment,
      premature arthropathy, and development of phalangeal epiphyseal dysplasia,
      resulting in brachydactyly was linked to COL2A1, the gene encoding proalpha1(II)
      collagen. Mutational analysis of the gene by exon sequencing identified a novel
      mutation in the C-propeptide region of the molecule. The glycine to aspartic acid
      change occurred in a region that is highly conserved in all fibrillar collagen
      molecules. The resulting phenotype does not fit easily into pre-existing
      subgroups of the type II collagenopathies, which includes spondyloepiphyseal
      dysplasia, and the Kniest, Strudwick, and Stickler dysplasias.

PMID- 12205111
TI  - Familial chronic nail candidiasis with ICAM-1 deficiency: a new form of chronic
      mucocutaneous candidiasis.

PMID- 12205112
TI  - Expression of wild type and mutant TSC2, but not TSC1, causes an increase in the
      G1 fraction of the cell cycle in HEK293 cells.

PMID- 12205113
TI  - Mutation in KCNQ1 that has both recessive and dominant characteristics.

PMID- 12205114
TI  - Heterozygous truncating mutation in the human homeobox gene GSH2 has no
      discernable phenotypic effect.

PMID- 12205115
TI  - Coping style, psychological distress, risk perception, and satisfaction in
      subjects attending genetic counselling for hereditary cancer.

PMID- 12205116
TI  - Genetic counselling for familial breast and ovarian cancer in Ontario.

PMID- 12205117
TI  - The use of audiotapes in consultations with women from high risk breast cancer
      families: a randomised trial.

PMID- 12205119
TI  - Parental attitude towards genetic testing for familial hypercholesterolaemia in
      children.

PMID- 12205120
TI  - Surviving campomelic dysplasia has the radiological features of the previously
      reported ischio-pubic-patella syndrome.

PMID- 12205121
TI  - Exceptionally mild Angelman syndrome phenotype associated with an incomplete
      imprinting defect.

PMID- 12205122
TI  - Transmission of an unbalanced (Y;1) translocation in Brittany, France.

PMID- 12205123
TI  - Subtelomeric rearrangements detected by FISH in three of 33 families with
      idiopathic mental retardation and minor physical anomalies.

PMID- 12205124
TI  - Survival in trisomy 13 and trisomy 18 cases ascertained from population based
      registers.

PMID- 12205125
TI  - Two novel aspartoacylase gene (ASPA) missense mutations specific to Norwegian and
      Swedish patients with Canavan disease.

PMID- 12205126
TI  - Molecular analysis of the aldolase B gene in patients with hereditary fructose
      intolerance from Spain.

PMID- 12205127
TI  - The intron 14 2140+5G>A variant in the low density lipoprotein receptor gene has
      no effect on plasma cholesterol levels.

PMID- 12205128
TI  - Allelic variants in the 5' non-coding region of the connexin32 gene: possible
      pitfalls in the diagnosis of X linked Charcot-Marie-Tooth neuropathy (CMTX).

PMID- 12205130
TI  - Functional properties of ryanodine receptors in hippocampal neurons change during
      early differentiation in culture.
AB  - 6-((4,4-difluoro-5,7-dimethyl-4-bora-3a,4a-diaza-s-indacene-3
      propionyl)amino)hexanoic acid ryanodine (BODIPY-ryanodine) binding and Ca(2+)
      imaging were used to study the properties of ryanodine receptors (RyRs) and
      cytoplasmic Ca(2+) (Ca) changes in neurons cultured from the embryonic rat
      hippocampus during the earliest stages of differentiation. Baseline Ca levels
      declined from 164 +/- 5 (SD) nM at early stages to 70 +/- 4 nM in differentiated
      neurons. Fluorescent BODIPY-ryanodine binding signals identified activated RyRs
      in somata, which were eliminated by removal of external Ca(2+) or by blockage of
      Ca(2+) entry through L-type but not N-type Ca(2+) channels. The GABA synthesis
      inhibitor 3-mercaptopropionic acid completely abolished ryanodine binding.
      Caffeine or K(+)-depolarization inhibited the activity of RyRs at very early
      stages of differentiation but had stimulatory effects at later stages after a
      network of processes had formed. BayK-8644 stimulated RyRs throughout all regions
      of all differentiating cells. The results suggest that in differentiating
      embryonic hippocampal neurons the activity of RyRs is maintained via Ca(2+)
      entering through L-type Ca(2+) channels. The mode of activation of L-type voltage
      gated Ca(2+) channels with either membrane depolarization or specific
      pharmacological agents affects the coupled activity of RyRs differently as
      neurons differentiate processes and networks.

PMID- 12205131
TI  - Regulation of the retinal bipolar cell mGluR6 pathway by calcineurin.
AB  - Glutamate produces a hyperpolarizing postsynaptic potential in ON bipolar cells
      by binding to the metabotropic receptor mGluR6 and subsequently closing a cation
      selective channel. It has been proposed that Ca(2+) influx through the cation
      channel triggers a depression of the synaptic potential. Here we report that this
      Ca(2+)-mediated depression requires activation of calcineurin, a
      Ca(2+)/calmodulin-regulated phosphatase. We measured glutamate-evoked currents
      (I(glu)) with whole cell recordings of ON bipolar cells in light-adapted retinal
      slices. Depression of I(glu) by Ca(2+) was prevented by inhibitors of calcineurin
      or by tightly buffering Ca(2+) with bis-(o-aminophenoxy)-N,N,N',N'-tetraacetic
      acid (BAPTA). However, when cells were dialyzed with BAPTA and a Ca(2+)
      independent form of calcineurin (CaN420), depression of I(glu) was restored.
      Similarly, CaN420 induced depression of I(glu) during continuous glutamate
      application, a protocol that ordinarily prevents depression. Analysis of changes
      in the amplitude of the cation-selective current (I(cat)) of cells that were
      dialyzed with high Ca(2+) (1 microM), or with BAPTA and CaN420, indicates that
      Ca(2+) depresses I(glu) by reducing I(cat) and that calcineurin acts via the same
      mechanism. Ca(2+)-mediated depression of I(glu) was not found to involve CaMKII,
      as inhibitors of CaMKII did not prevent this depression nor did they affect the
      sensitivity of the response to small changes in the concentration of mGluR6
      agonist. Our data suggest that Ca(2+) and calcineurin may play an adaptive role
      at the synapse between photoreceptor and ON bipolar cells, closing postsynaptic
      cation channels that are opened by a drop in synaptic glutamate levels during
      prolonged photoreceptor illumination.

PMID- 12205132
TI  - Sensorimotor integration in human postural control.
AB  - It is generally accepted that human bipedal upright stance is achieved by
      feedback mechanisms that generate an appropriate corrective torque based on body
      sway motion detected primarily by visual, vestibular, and proprioceptive sensory
      systems. Because orientation information from the various senses is not always
      available (eyes closed) or accurate (compliant support surface), the postural
      control system must somehow adjust to maintain stance in a wide variety of
      environmental conditions. This is the sensorimotor integration problem that we
      investigated by evoking anterior-posterior (AP) body sway using pseudorandom
      rotation of the visual surround and/or support surface (amplitudes 0.5-8 degrees
      ) in both normal subjects and subjects with severe bilateral vestibular loss
      (VL). AP rotation of body center-of-mass (COM) was measured in response to six
      conditions offering different combinations of available sensory information.
      Stimulus-response data were analyzed using spectral analysis to compute transfer
      functions and coherence functions over a frequency range from 0.017 to 2.23 Hz.
      Stimulus-response data were quite linear for any given condition and amplitude.
      However, overall behavior in normal subjects was nonlinear because gain decreased
      and phase functions sometimes changed with increasing stimulus amplitude.
      "Sensory channel reweighting" could account for this nonlinear behavior with
      subjects showing increasing reliance on vestibular cues as stimulus amplitudes
      increased. VL subjects could not perform this reweighting, and their stimulus
      response behavior remained quite linear. Transfer function curve fits based on a
      simple feedback control model provided estimates of postural stiffness, damping,
      and feedback time delay. There were only small changes in these parameters with
      increasing visual stimulus amplitude. However, stiffness increased as much as 60%
      with increasing support surface amplitude. To maintain postural stability and
      avoid resonant behavior, an increase in stiffness should be accompanied by a
      corresponding increase in damping. Increased damping was achieved primarily by
      decreasing the apparent time delay of feedback control rather than by changing
      the damping coefficient (i.e., corrective torque related to body-sway velocity).
      In normal subjects, stiffness and damping were highly correlated with body mass
      and moment of inertia, with stiffness always about 1/3 larger than necessary to
      resist the destabilizing torque due to gravity. The stiffness parameter in some
      VL subjects was larger compared with normal subjects, suggesting that they may
      use increased stiffness to help compensate for their loss. Overall results show
      that the simple act of standing quietly depends on a remarkably complex
      sensorimotor control system.

PMID- 12205133
TI  - Spontaneous miniature hyperpolarizations affect threshold for action potential
      generation in mudpuppy cardiac neurons.
AB  - Mudpuppy parasympathetic neurons exhibit spontaneous miniature hyperpolarizations
      (SMHs) that are generated by potassium currents, which are spontaneous miniature
      outward currents (SMOCs), flowing through clusters of large conductance voltage-
      and calcium (Ca(2+))-activated potassium (BK) channels. The underlying SMOCs are
      initiated by a Ca(2+)-induced Ca(2+) release (CICR) mechanism. Perforated-patch
      whole cell voltage recordings were used to determine whether activation of SMHs
      contributed to action potential (AP) repolarization or affected the latency to AP
      generation. Blockade of BK channels by iberiotoxin (IBX, 100 nM) slowed AP
      repolarization and increased AP duration. Treatment with omega-conotoxin GVIA (3
      microM) or nifedipine (10 microM) to inhibit Ca(2+) influx through N- or L-type
      voltage-dependent calcium channels (VDCCs), respectively, also decreased the rate
      of AP repolarization and increased AP duration. Elimination of CICR by treatment
      with either thapsigargin (1 microM) or ryanodine (10 microM) produced no
      significant change in AP repolarization or duration. Blockade of BK channels with
      IBX and inhibition of N-type VDCCs with omega-conotoxin GVIA, but not inhibition
      of L-type VDCCs with nifedipine, decreased the latency of AP generation. A
      decrease in latency to AP generation occurred with elimination of SMHs by
      inhibition of CICR following treatment with thapsigargin. Ryanodine treatment
      decreased AP latency in three of six cells. Apamin (100 nM) had no affect on AP
      repolarization, duration, or latency to AP generation, but did decrease the
      hyperpolarizing afterpotential (HAP). Inhibition of L-type VDCCs by nifedipine
      also decreased HAP amplitude. Inhibition of CICR by either thapsigargin or
      ryanodine treatment increased the number of APs generated with long depolarizing
      current pulses, whereas exposure to IBX or omega-conotoxin GVIA depressed
      excitability. We conclude that CICR, the process responsible for SMH generation,
      represents a unique mechanism to modulate the response to subthreshold
      depolarizing currents that drive the membrane potential toward the threshold for
      AP initiation but does not contribute to AP repolarization. Subthreshold
      depolarizations would not activate sufficient numbers of VDCCs to allow Ca(2+)
      influx to elevate [Ca(2+)](i) to the extent needed to directly activate nearby BK
      channels. However, the elevation in [Ca(2+)](i) is sufficient to trigger CICR
      from ryanodine-sensitive Ca(2+) stores. Thus CICR acts as an amplification
      mechanism to trigger a local elevation of [Ca(2+)](i) near a cluster of BK
      channels to activate these channels at negative levels of membrane potential.

PMID- 12205134
TI  - Responses of primate visual cortical V4 neurons to simultaneously presented
      stimuli.
AB  - We report here results from 45 primate V4 visual cortical neurons to the
      preattentive presentations of seven different patterns located in two separate
      areas of the same receptive field and to combinations of the patterns in the two
      locations. For many neurons, we could not determine any clear relationship for
      the responses to two simultaneous stimuli. However, for a substantial fraction of
      the neurons we found that the firing rate was well modeled as the maximum firing
      rate of each stimulus presented separately. It has previously been proposed that
      taking the maximum of the inputs ("MAX" operator) could be a useful operation for
      neurons in visual cortex, although there has until now been little direct
      physiological evidence for this hypothesis. Our results here provide direct
      support for the hypothesis that the MAX operator plays a significant (although
      certainly not exclusive) role in generating the receptive field properties of
      visual cortical neurons.

PMID- 12205135
TI  - Responses of reticulospinal neurons in intact lamprey to pitch tilt.
AB  - In the swimming lamprey, a postural control system maintains a definite
      orientation of the animal's longitudinal axis in relation to the horizon (pitch
      angle). Operation of this system is based on vestibular reflexes. Important
      elements of the postural network are the reticulospinal (RS) neurons, which are
      driven by vestibular input and transmit commands for postural corrections from
      the brain stem to the spinal cord. Here we describe responses to vestibular
      stimulation (rotation of the animal in the pitch plane) in RS neurons of intact
      lampreys. The activity of neurons was recorded from their axons in the spinal
      cord by chronically implanted arrays of macroelectrodes. From the multielectrode
      recordings of mass activity, discharges in individual axons were extracted by
      means of a spike-sorting program, and the axon position in the spinal cord and
      its conduction velocity were determined. Vestibular stimulation was performed by
      rotating the animal in steps of 45 degrees throughout 360 degrees or by
      periodical "trapezoid" tilts between the nose-up and -down positions. Typically,
      the RS neurons exhibited both dynamic responses (activity during movement) and
      static responses (activity in a new sustained position). The neurons were
      classified into two groups according to their pattern of response. Group UP
      neurons responded preferentially to nose-up rotation with maximal activity at 0
      135 degrees up. Group DOWN neurons responded preferentially to nose-down rotation
      with maximal activity at 0-135 degrees down. Neurons of the two groups also
      differed in the position of their axons in the spinal cord and axonal conduction
      velocity. An increase in water temperature, which presumably causes a downward
      turn in swimming lampreys, affected the activity in the UP and DOWN groups
      differently, so that the ratio UP responses to DOWN responses increased. We
      suggest that the UP and DOWN groups mediate the opposing vestibular reflexes and
      cause the downward and upward turns of the animal, respectively. The lamprey will
      stabilize the orientation in the pitch plane at which the effects of UP and DOWN
      groups are equal to each other. In addition to the main test (rotation in the
      pitch plane), the animals were also tested by rotation in the transverse (roll)
      plane. It was found that 22% of RS neurons responding to pitch tilts also
      responded to roll tilts. The overlap between the pitch and roll populations
      suggests that the RS pathways are partly shared by the pitch and roll control
      systems.

PMID- 12205136
TI  - Allopregnanolone activates GABA(A) receptor/Cl(-) channels in a multiphasic
      manner in embryonic rat hippocampal neurons.
AB  - Although 3alpha-substituted metabolites of progesterone are well established to
      interact with GABA(A) receptor/Cl(-) channels, the nature of the interaction(s)
      remains uncertain. We used patch-clamp recording to study the interaction with
      GABA(A) receptor/Cl(-) channels expressed by embryonic hippocampal neurons
      differentiating in culture and nonneuronal cells transfected with GABA(A)
      receptor subunits. Allopregnanolone primarily induced multiphasic current
      responses in neurons, which were eliminated by bicuculline, an antagonist of GABA
      at GABA(A) receptor/Cl(-) channels. Similar multiphasic responses blocked by
      bicuculline were induced by allopregnanollone in nonneuronal cells transfected
      with alpha(1) and gamma(2) subunits, indicating that the steroid activation of
      GABA(A) receptor/Cl(-) channels occurred independently of GABA. Fluctuation
      analyses of current responses to allopregnanolone and GABA revealed underlying
      channel activities with similar estimated unitary properties. However, although
      both agonists activated Cl(-) channels with similar estimated short and long
      burst-length durations, most of those stimulated by the steroid were short, while
      most of those opened by GABA were long. Allopregnanolone potentiated GABA-evoked
      Cl(-) currents in nonneuronal cells transfected with alpha(1) and beta(2) or
      beta(3) subunits, which did not exhibit multiphasic responses to the steroid,
      indicating another, independent action of the steroid at activated receptors.
      Pertussis toxin treatment eliminated the low-amplitude current and attenuated the
      high-amplitude current induced by allopregnanolone in a reversible manner.
      Mastoparan, which activates G proteins directly, triggered a high-amplitude
      current after a delay, which was blocked by bicuculline. The results indicate
      that allopregnanolone interacts with GABA(A) receptor/Cl(-) channels expressed by
      embryonic hippocampal neurons in multiple ways, some of which are mediated by G
      proteins.

PMID- 12205137
TI  - Associative interactions within the superficial layers of the entorhinal cortex
      of the guinea pig.
AB  - Associative fiber systems in the entorhinal cortex (EC) have been extensively
      studied in different mammals with tracing techniques. The largest contingent of
      intra-EC cortico-cortical fibers runs in the superficial layers and is
      distributed predominantly within longitudinal cortical bands. We studied the
      patterns of intrinsic EC connectivity in the in vitro isolated guinea pig brain
      preparation by performing current-source density analysis of field potential
      laminar profiles recorded with multi-channel silicon probes. The response pattern
      evoked by stimulation of the lateral olfactory tract was utilized to identify the
      lateral (l-EC) and medial (m-EC) entorhinal cortex. Stimulation of the deep
      layers did not evoke consistent responses. Local stimulation of the superficial
      layers in different portions of the EC induced an early, possibly direct response
      restricted to layer II-III in the close proximity to the stimulating electrode,
      followed by a late potential in the superficial layer I, that propagated at
      distance with a progressively increasing latency. The monosynaptic nature of the
      delayed response was verified by applying a pairing test. The results
      demonstrated that stimulation in the rostral-medial part of the EC generated
      activity restricted to the rostral pole of the l-EC, stimulation of the m-EC
      induced an associative activation that propagated rostrocaudally within the m-EC,
      stimulation of the caudal pole of the m-EC induced an additional response
      directed laterally, and stimulation of the lateral band of the EC determined a
      prominent longitudinal propagation of neuronal activity, but also induced
      associative potentials that propagated medially. The results are in partial
      agreement with the general picture derived from the anatomical studies performed
      in different species. Even though the largest associative interactions between
      superficial layers are restricted within either the m-EC or the l-EC, both
      rostral and caudal stimuli in the EC region close to the rhinal sulcus induced
      activity that propagated across the border between l- and m-EC.

PMID- 12205138
TI  - Inhibitory synchronization of bursting in biological neurons: dependence on
      synaptic time constant.
AB  - Using the dynamic clamp technique, we investigated the effects of varying the
      time constant of mutual synaptic inhibition on the synchronization of bursting
      biological neurons. For this purpose, we constructed artificial half-center
      circuits by inserting simulated reciprocal inhibitory synapses between identified
      neurons of the pyloric circuit in the lobster stomatogastric ganglion. With
      natural synaptic interactions blocked (but modulatory inputs retained), these
      neurons generated independent, repetitive bursts of spikes with cycle period
      durations of approximately 1 s. After coupling the neurons with simulated
      reciprocal inhibition, we selectively varied the time constant governing the rate
      of synaptic activation and deactivation. At time constants <or=100 ms, bursting
      was coordinated in an alternating (anti-phase) rhythm. At longer time constants
      (>400 ms), bursts became phase-locked in a fully overlapping pattern with little
      or no phase lag and a shorter period. During the in-phase bursting, the higher
      frequency spiking activity was not synchronized. If the circuit lacked a robust
      periodic burster, increasing the time constant evoked a sharp transition from out
      of-phase oscillations to in-phase oscillations with associated intermittent phase
      jumping. When a coupled periodic burster neuron was present (on one side of the
      half-center circuit), the transition was more gradual. We conclude that the
      magnitude and stability of phase differences between mutually inhibitory neurons
      varies with the ratio of burst cycle period duration to synaptic time constant
      and that cellular bursting (whether periodic or irregular) can adopt in-phase
      coordination when inhibitory synaptic currents are sufficiently slow.

PMID- 12205139
TI  - Low-frequency oscillations (<0.3 Hz) in the electromyographic (EMG) activity of
      the human trapezius muscle during sleep.
AB  - The surface electromyographic (EMG) signal from right and left trapezius muscles
      and the heart rate were recorded over 24 h in 27 healthy female subjects. The
      root-mean-square (RMS) value of the surface EMG signals and the heartbeat
      interval time series were calculated with a time resolution of 0.2 s. The EMG
      activity during sleep showed long periods with stable mean amplitude, modulated
      by rhythmic components in the frequency range 0.05-0.2 Hz. The ratio between the
      amplitude of the oscillatory components and the mean amplitude of the EMG signal
      was approximately constant over the range within which the phenomenon was
      observed, corresponding to a peak-to-peak oscillatory amplitude of approximately
      10% of the mean amplitude. The duration of the periods with stable mean amplitude
      ranged from a few minutes to approximately 1 h, usually interrupted by a sudden
      change in the activity level or by cessation of the muscle activity. Right and
      left trapezius muscles presented the same pattern of FM. In supplementary
      experiments, rhythmic muscle activity pattern was also demonstrated in the upper
      extremity muscles of deltoid, biceps, and forearm flexor muscles. There was no
      apparent association between the rhythmic components in the muscle activity
      pattern and the heart rate variability. To our knowledge, this is the first time
      that the above-described pattern of EMG activity during sleep is documented. On
      reanalysis of earlier recorded trapezius motor unit firing pattern in experiments
      on awake subjects in a situation with mental stress, low-FM of firing with
      similar frequency content was detected. Possible sources of rhythmic excitation
      of trapezius motoneurons include slow-wave cortical oscillations represented in
      descending cortico-spinal pathways, and/or activation by monoaminergic pathways
      originating in the brain stem reticular formation. The analysis of muscle
      activity patterns may provide an important new tool to study neural mechanisms in
      human sleep.

PMID- 12205140
TI  - Effect of tactile inputs on thalamic responses to noxious colorectal distension
      in rat.
AB  - Recent discoveries of visceral nociceptive inputs sharing the classical tactile
      pathway in the dorsal-column medial lemniscus system have opened a new venue for
      the investigation of somatovisceral interactions. The current study was designed
      to determine whether somatic innocuous inputs modulate visceral nociceptive
      transmission at the thalamic level. The investigation was carried out by means of
      extracellular single-unit recordings in the ventroposterior lateral nucleus of
      the thalamus in rats anesthetized with pentobarbital. Noxious visceral
      stimulation was achieved by reproducible colorectal distension (CRD, 20-80 mmHg)
      with a balloon catheter. Tactile stimulation was delivered by means of a feedback
      controlled mechanical stimulator. The response of the neurons to CRD was compared
      before and after the conditioning procedure by giving tactile stimulation either
      immediately before CRD or overlapping it. Twenty-five ventroposterior lateral
      (VPL) thalamic neurons were found among numerous tactile-only neurons to have
      convergent inputs from both tactile and visceral sources. Their responses to CRD
      were excitatory (19), inhibitory (4), or bimodal. When cutaneous tactile stimuli
      were delivered before CRD, the responses were reduced in 18 cases. The reduction,
      however, was usually short-lasting, immediately following tactile stimulation and
      could not be enhanced by a prolonged conditioning procedure. It was unlikely to
      be attributable to neuronal habituation as the inverted procedure, CRD
      stimulation before tactile, often produced the opposite effect, that is, an
      enhanced response to skin stimulation. Repeated CRD could bring about
      sensitization of the responses of thalamic neurons as manifested by increased
      spontaneous discharge, lowered response threshold, and increased response level.
      Under such circumstances, the original effect of tactile stimulation on CRD
      responses could be weakened. In conclusion, tactile stimulation may in most
      circumstances inhibit thalamic neuronal responses to visceral nociceptive input
      produced by CRD. However, the effect appears to be mild and short-lasting at the
      individual neuronal level in the VPL thalamus.

PMID- 12205141
TI  - Muscarinic activation of a cation current and associated current noise in
      entorhinal-cortex layer-II neurons.
AB  - The effects of muscarinic stimulation on the membrane potential and current of in
      situ rat entorhinal-cortex layer-II principal neurons were analyzed using the
      whole cell, patch-clamp technique. In current-clamp experiments, application of
      carbachol (CCh) induced a slowly developing, prolonged depolarization initially
      accompanied by a slight decrease or no significant change in input resistance. By
      contrast, in a later phase of the depolarization input resistance appeared
      consistently increased. To elucidate the ionic bases of these effects, voltage
      clamp experiments were then carried out. In recordings performed in nearly
      physiological ionic conditions at the holding potential of -60 mV, CCh
      application promoted the slow development of an inward current deflection
      consistently associated with a prominent increase in current noise. Similarly to
      voltage responses to CCh, this inward-current induction was abolished by the
      muscarinic antagonist, atropine. Current-voltage relationships derived by
      applying ramp voltage protocols during the different phases of the CCh-induced
      inward-current deflection revealed the early induction of an inward current that
      manifested a linear current/voltage relationship in the subthreshold range and
      the longer-lasting block of an outward K(+) current. The latter current could be
      blocked by 1 mM extracellular Ba(2+), which allowed us to study the CCh-induced
      inward current (I(CCh)) in isolation. The extrapolated reversal potential of the
      isolated I(CCh) was approximately 0 mV and was not modified by complete
      substitution of intrapipette K(+) with Cs(+). Moreover, the extrapolated I(CCh)
      reversal shifted to approximately -20 mV on removal of 50% extracellular Na(+).
      These results are consistent with I(CCh) being a nonspecific cation current.
      Finally, noise analysis of I(CCh) returned an estimated conductance of the
      underlying channels of approximately 13.5 pS. We conclude that the depolarizing
      effect of muscarinic stimuli on entorhinal-cortex layer-II principal neurons
      depends on both the block of a K(+) conductance and the activation of a "noisy"
      nonspecific cation current. We suggest that the membrane current fluctuations
      brought about by I(CCh) channel noise may facilitate the "theta" oscillatory
      dynamics of these neurons and enhance firing reliability and synchronization.

PMID- 12205142
TI  - Coexistence of functional IP(3) and ryanodine receptors in vagal sensory neurons
      and their activation by ATP.
AB  - Intracellular photorelease of caged D-myo-inositol 1,4,5-trisphosphate (IP(3)),
      caffeine application, and immunofluorescence confocal microscopy were used to
      determine that D-myo-inositol 1,4,5-trisphosphate receptors (IP(3)Rs) and
      ryanodine receptors (RyRs) coexist in rabbit vagal sensory nodose ganglion
      neurons (NGNs). ATP, an extracellular physiological signaling molecule,
      consistently evoked robust transient increases in cytosolic free Ca(2+)
      concentration (Ca(2+) transients). ATP applied in Ca(2+)-free physiological
      saline elicited Ca(2+) transients that averaged approximately 70% of the
      amplitude of transients evoked in the presence of extracellular Ca(2+). The
      component of the ATP-evoked Ca(2+) transient that was independent of
      extracellular Ca(2+) corresponds to Ca(2+) release from intracellular stores.
      This release component was sensitive to the pharmacological antagonists
      pyridoxalphosphate-6-azophenyl-2',4'-disulphonic acid (PPADS), U73122, neomycin,
      and heparin (13.5-15 kD), indicating that P2 purinoreceptors (P2Y) and the IP(3)
      signaling pathway are required for ATP-evoked Ca(2+) release. Additionally, a
      portion of ATP-evoked Ca(2+) release was inhibited by ryanodine, a selective
      blocker of RyRs. The ryanodine-insensitive component (approximately 70%) of ATP
      evoked Ca(2+) release corresponds to IP(3)-induced Ca(2+) release via IP(3)Rs,
      while the ryanodine-sensitive component (approximately 30%) corresponds to
      consequent Ca(2+)-induced Ca(2+) release (CICR) via RyRs. These results indicate
      that functional IP(3)Rs and RyRs coexist in nodose neurons and that both IP(3)
      induced Ca(2+) release and CICR can be activated by ATP.

PMID- 12205143
TI  - Effects of voluntary blinks on saccades, vergence eye movements, and saccade
      vergence interactions in humans.
AB  - Blinks are known to change the kinematic properties of horizontal saccades,
      probably by influencing the saccadic premotor circuit. The neuronal basis of this
      effect could be explained by changes in the activity of omnipause neurons in the
      nucleus raphe interpositus or in the saccade-related burst neurons of the
      superior colliculus. Omnipause neurons cease discharge during both saccades and
      vergence movements. Because eyelid blinks can influence both sets of neurons, we
      hypothesized that blinks would influence the kinematic parameters of saccades in
      all directions, vergence, and saccade-vergence interactions. To test this
      hypothesis, we investigated binocular eye and lid movements in five normal
      healthy subjects with the magnetic search coil technique. The subjects performed
      conjugate horizontal and vertical saccades from gaze straight ahead to targets at
      20 degrees up, down, right, or left while either attempting not to blink or
      voluntarily blinking. While following the same blink instruction, subjects made
      horizontal vergence eye movements of 7 degrees and combined saccade-vergence
      movements with a version amplitude of 20 degrees. The movements were performed
      back and forth from two targets simultaneously presented nearby (38 cm) and more
      distant (145 cm). Small vertical saccades accompanied most vergence movements.
      These results show that blinks change the kinematics (saccade duration, peak
      velocity, peak acceleration, peak deceleration) of not only horizontal but also
      of vertical saccades, of horizontal vergence eye movements, and of combined
      saccade-vergence eye movements. Peak velocity, acceleration, and deceleration of
      eye movements were decreased on the average by 30%, and their duration increased
      by 43% on the average when they were accompanied by blinks. The blink effect was
      time dependent with respect to saccade and vergence onset: the greatest effect
      occurred 100 ms prior to saccade onset, whereas there was no effect when the
      blink started after saccade onset. The effects of blinks on saccades and
      vergence, which are tightly coupled to latency, support the hypothesis that
      blinks cause profound spatiotemporal perturbations of the eye movements by
      interfering with the normal saccade/vergence premotor circuits. However, the
      measured effect may to a certain degree but not exclusively be explained by
      mechanical interference.

PMID- 12205144
TI  - Reflections of efferent activity in rotational responses of chinchilla vestibular
      afferents.
AB  - To study presumed efferent-mediated responses, we determined if afferents
      responded to head rotations that stimulated semicircular canals other than the
      organ being innervated. To minimize stimulation of an afferent's own canal, its
      plane was placed nearly orthogonal to the rotation plane. Otolith units were
      tested in a horizontal head position with the ear placed near the rotation axis
      to minimize linear forces. Under these circumstances, angular-velocity trapezoids
      (2-s ramps, 2-s plateau) evoked excitatory responses for both rotation
      directions. These type III responses were considerably larger in decerebrate than
      in anesthetized preparations. In addition to their being exclusively excitatory,
      the responses resembled those obtained with electrical stimulation of efferent
      pathways in including per-stimulus and more prolonged post-stimulus components
      and in being larger in irregularly discharging than in regularly discharging
      units. Responses, which were not seen for rotations <80 degrees/s, grew as
      velocity increased between 80 and 500 degrees/s but were seldom larger than 20
      spikes/s. Complete section of the VIIIth nerve abolished type III responses,
      leaving conventional afferent responses intact. To study the separate
      contributions of canals on the two sides, responses were compared when the
      labyrinths were intact and when the ipsilateral or contralateral horizontal canal
      was mechanically inactivated. Both sides contributed to the efferent-mediated
      responses. That afferents could be influenced from the contralateral labyrinth
      was confirmed with the use of unilateral galvanic currents. Following
      inactivation, excitatory responses were produced by rotations exciting or
      inhibiting the intact horizontal canal with the responses resulting from
      excitatory rotations being much larger. Such a response asymmetry is consistent
      with a semicircular-canal origin for the type III responses. A similar asymmetry
      was seen in the post-stimulus responses to contralateral cathodal (excitatory)
      and anodal (inhibitory) galvanic currents. We conclude that the efferent system
      receives a sufficiently powerful vestibular input from both the ipsilateral and
      contralateral labyrinths to affect afferent discharge.

PMID- 12205145
TI  - Suppression by zinc of AMPA receptor-mediated synaptic transmission in the
      retina.
AB  - Zinc is strikingly co-localized with glutamate-containing vesicles in the
      synaptic terminals of retinal photoreceptors, and it is thought to be co-released
      with glutamate onto postsynaptic neurons such as horizontal cells and bipolar
      cells. Here we examined exogenous zinc modulation of glutamate receptors on
      cultured retinal horizontal cells using patch-clamp recording and endogenous zinc
      effect on intact horizontal cells using intracellular recording techniques.
      Application of 3, 30, and 300 microM zinc reduced the whole cell peak current of
      response to 200 microM glutamate by 2, 30, and 56%, respectively. Zinc
      suppression of glutamate response persisted in the presence of 10 microM
      cyclothiazide (CTZ). Glutamate responses of outside-out patches were completely
      abolished by 30 microM 1-(4-aminophenyl)-4-methyl-7,8-methylenedioxy-5H-2,3
      benzodiazepine (GYKI 52466), and the receptor desensitization was blocked by 30
      microM CTZ, indicating that receptor target for the zinc action on horizontal
      cells is alpha-amino-3-hydroxy-5-methyl-4-isoxazoleproponic acid (AMPA)
      receptors. Zinc decreased the amplitude of outside-out patch peak current without
      an effect on either its 10-90% rise time or the rate of receptor desensitization.
      Dose-response curves for glutamate show that zinc reduced the maximal current
      evoked by glutamate and increased EC(50) from 50 +/- 3 to 70 +/- 6 microM without
      changing the Hill coefficient. Chelation of endogenous zinc with 1 mM Ca-EDTA
      depolarized horizontal cells in the intact retina by 3 mV, consistent with relief
      of the partial glutamate receptor inhibition by zinc. Overall, the results
      describe a unimodal form of zinc modulation of AMPA-type glutamate receptor
      responses not previously described in native neuronal preparations and a novel
      role for endogenous zinc in modulating neurotransmission.

PMID- 12205146
TI  - Frequency response properties of lateral line superficial neuromasts in a vocal
      fish, with evidence for acoustic sensitivity.
AB  - The mechanosensory lateral line of fish is a hair cell based sensory system that
      detects water motion using canal and superficial neuromasts. The trunk lateral
      line of the plainfin midshipman fish, Porichthys notatus, only has superficial
      neuromasts. The posterior lateral line nerve (PLLn) therefore innervates trunk
      superficial neuromasts exclusively and provides the opportunity to investigate
      the physiological responses of these receptors without the confounding influence
      of canal organs. We recorded single-unit activity from PLLn primary afferents in
      response to a vibrating sphere stimulus calibrated to produce an equal velocity
      across frequencies. Threshold tuning, isovelocity, and input/output curves were
      constructed using spike rate and vector strength, a measure of phase locking of
      spike times to the stimulus waveform. All units responded maximally to
      frequencies of 20-50 Hz. Units were classified as low-pass, band-pass, broadly
      tuned, or complex based on the shapes of tuning and isovelocity curves between 20
      and 100 Hz. A 100 Hz stimulus caused an increase in spike rate in almost 50%, and
      significant synchronization in >80%, of all units. Midshipman vocalizations
      contain significant energy at and below 100 Hz, so these results demonstrate that
      the midshipman peripheral lateral line system can encode these acoustic signals.
      These results provide the first direct demonstration that units innervating
      superficial neuromasts in a teleost fish have heterogeneous frequency response
      properties, including an upper range of sensitivity that overlaps spectral peaks
      of behaviorally relevant acoustic stimuli.

PMID- 12205147
TI  - Inhibitory interactions between spiny projection neurons in the rat striatum.
AB  - The spiny projection neurons are by far the most numerous type of striatal
      neuron. In addition to being the principal projection neurons of the striatum,
      the spiny projection neurons also have an extensive network of local axon
      collaterals by which they make synaptic connections with other striatal
      projection neurons. However, up to now there has been no direct physiological
      evidence for functional inhibitory interactions between spiny projection neurons.
      Here we present new evidence that striatal projection neurons are interconnected
      by functional inhibitory synapses. To examine the physiological properties of
      unitary inhibitory postsynaptic potentials (IPSPs), dual intracellular recordings
      were made from pairs of spiny projection neurons in brain slices of adult rat
      striatum. Synaptic interactions were found in 9 of 45 pairs of neurons using
      averages of 200 traces that were triggered by a single presynaptic action
      potential. In all cases, synaptic interactions were unidirectional, and no
      bidirectional interactions were detected. Unitary IPSPs evoked by a single
      presynaptic action potential had a peak amplitude ranging from 157 to 319 microV
      in different connections (mean: 277 +/- 46 microV, n = 9). The percentage of
      failures of single action potentials to evoke a unitary IPSP was estimated and
      ranged from 9 to 63% (mean: 38 +/- 14%, n = 9). Unitary IPSPs were reversibly
      blocked by bicuculline (n = 4) and had a reversal potential of -62.4 +/- 0.7 mV
      (n = 5), consistent with GABA-mediated inhibition. The findings of the present
      study correlate very well with anatomical evidence for local synaptic
      connectivity between spiny projection neurons and suggest that lateral inhibition
      plays a significant role in the information processing operations of the
      striatum.

PMID- 12205148
TI  - Ryanodine receptors contribute to cGMP-induced late-phase LTP and CREB
      phosphorylation in the hippocampus.
AB  - We previously found that the nitric oxide (NO)-cGMP-cGMP-dependent protein kinase
      (PKG) signaling pathway acts in parallel with the cAMP-cAMP-dependent protein
      kinase (PKA) pathway to produce protein and RNA synthesis-dependent late-phase
      long-term potentiation (L-LTP) and cAMP response element-binding protein (CREB)
      phosphorylation in the CA1 region of mouse hippocampus. We have now investigated
      the possible involvement of a downstream target of PKG, ryanodine receptors. L
      LTP can be induced by either multiple-train tetanization, NO or 8-Br-cGMP paired
      with one-train tetanization, or the cAMP activator forskolin, and all three types
      of potentiation are accompanied by an increase in phospho-CREB immunofluorescence
      in the CA1 cell body area. Both the potentiation and the increase in phospho-CREB
      immunofluorescence induced by multiple-train tetanization or 8-Br-cGMP paired
      with one-train tetanization are reduced by prolonged perfusion with ryanodine,
      which blocks Ca(2+) release from ryanodine-sensitive Ca(2+) stores. By contrast,
      neither the potentiation nor the increase in immunofluorescence induced by
      forskolin are reduced by depletion of ryanodine and inositol-1,4,5-triphosphate
      (IP3)-sensitive Ca(2+) stores. These results suggest that NO, cGMP, and PKG cause
      release of Ca(2+) from ryanodine-sensitive stores, which in turn causes
      phosphorylation of CREB in parallel with PKA during the induction of L-LTP.

PMID- 12205149
TI  - GluR2-dependent properties of AMPA receptors determine the selective
      vulnerability of motor neurons to excitotoxicity.
AB  - AMPA receptor-mediated excitotoxicity has been implicated in the selective motor
      neuron loss in amyotrophic lateral sclerosis. In some culture models, motor
      neurons have been shown to be selectively vulnerable to AMPA receptor agonists
      due to Ca(2+) influx through Ca(2+)-permeable AMPA receptors. Because the absence
      of GluR2 in AMPA receptors renders them highly permeable to Ca(2+) ions, it has
      been hypothesized that the selective vulnerability of motor neurons is due to
      their relative deficiency in GluR2. However, conflicting evidence exists about
      the in vitro and in vivo expression of GluR2 in motor neurons, both at the mRNA
      and at the protein level. In this study, we quantified electrophysiological
      properties of AMPA receptors, known to be dependent on the relative abundance of
      GluR2: sensitivity to external polyamines, rectification index, and relative
      Ca(2+) permeability. Cultured rat spinal cord motor neurons were compared with
      dorsal horn neurons (which are resistant to excitotoxicity) and with motor
      neurons that survived an excitotoxic insult. Motor neurons had a higher
      sensitivity to external polyamines, a lower rectification index, and a higher
      relative Ca(2+) permeability ratio than dorsal horn neurons. These findings
      confirm that motor neurons are relatively deficient in GluR2. The AMPA receptor
      properties correlated well with each other and with the selective vulnerability
      of motor neurons because motor neurons surviving an excitotoxic event had similar
      characteristics as dorsal horn neurons. These data indicate that the relative
      abundance of GluR2 in functional AMPA receptors may be a major determinant of the
      selective vulnerability of motor neurons to excitotoxicity in vitro.

PMID- 12205150
TI  - Local circuit properties underlying cortical reorganization.
AB  - Peripheral denervation has been shown to cause reorganization of the deafferented
      somatotopic region in primary somatosensory cortex (S1). However, the basic
      mechanisms that underlie reorganization are not well understood. In the
      experiments described in this paper, a novel in vivo/in vitro preparation of
      adult rat S1 was used to determine changes in local circuit properties associated
      with the denervation-induced plasticity of the cortical representation in rat S1.
      In the present studies, deafferentation of rat S1 was induced by cutting the
      radial and median nerves in the forelimb of adult rats, resulting in a rapid
      shift of the location of the forepaw/lower jaw border; the amount of the shift
      increased over the times assayed, through 28 days after denervation. The
      locations of both borders (i.e., original and reorganized) were marked with vital
      dyes, and slices from the marked region were used for whole-cell recording.
      Responses were evoked using electrical stimulation of supragranular S1 and
      recorded in supragranular neurons close to either the original or reorganized
      border. For each neuron, postsynaptic potentials (PSPs) were evoked by
      stimulation of fibers that crossed the border site (CB stim) and by equivalent
      stimulation that did not cross (NCB stim). Monosynaptic inhibitory postsynaptic
      potentials (IPSPs) were also examined after blocking excitatory transmission with
      15 microM CNQX plus 100 microM DL-APV. The amplitudes of PSPs and IPSPs were
      compared between CB and NCB stimulation to quantify effects of the border sites
      on excitation and inhibition. Previous results using this preparation in the
      normal (i.e., without induced plasticity) rat S1 demonstrated that at a normal
      border both PSPs and IPSPs were smaller when evoked with CB stimulation than with
      NCB stimulation. For most durations of denervation, a similar bias (i.e., smaller
      responses with CB stimulation) for PSPs and IPSPs was observed at the site of the
      novel reorganized border, while no such bias was observed at the suppressed
      original border site. Thus changes in local circuit properties (excitation and
      inhibition) can reflect larger-scale changes in cortical organization. However,
      specific dissociations between these local circuit properties and the presence of
      the novel border at certain durations of denervation were also observed,
      suggesting that there are several intracortical processes contributing to
      cortical reorganization over time and that excitation and inhibition may
      contribute differentially to them.

PMID- 12205151
TI  - Neuroprotective effects of increased extracellular Ca(2+) during aglycemia in
      white matter.
AB  - We investigated the effects of extracellular [Ca(2+)] ([Ca(2+)](o)) on aglycemia
      induced dysfunction and injury in adult rat optic nerves. Compound action
      potentials (CAPs) from adult rat optic nerve were recorded in vitro, and the area
      under the CAP was used to monitor nerve function before and after 1 h periods of
      aglycemia. In control artificial cerebrospinal fluid (ACSF) containing 2 mM
      Ca(2+), CAP function fell after 29.9 +/- 1.5 (SE) min and recovered to 48.8 +/-
      3.9% following aglycemia. Reducing bath [Ca(2+)] during aglycemia progressively
      improved recovery. For example, in Ca(2+)-free ACSF, the CAP recovered to 99.1 +/
      3.8%. Paradoxically, increasing bath [Ca(2+)] also improved recovery from
      aglycemia. In 5 or 10 mM bath [Ca(2+)], CAP recovered to 78.8 +/- 9.2 or 91.6 +/-
      5.2%, respectively. The latency to CAP failure during aglycemia increased as a
      function of bath [Ca(2+)] from 0 to 10 mM. Increasing bath [Mg(2+)] from 2 to 5
      or 10 mM, with bath [Ca(2+)] held at 2 mM, increased latency to CAP failure with
      aglycemia and improved recovery from this insult. [Ca(2+)](o) recorded with
      calcium-sensitive microelectrodes in control ACSF, dropped reversibly during
      aglycemia from 1.54 +/- 0.03 to 0.45 +/- 0.04 mM. In the presence of higher
      ambient levels of bath [Ca(2+)] (i.e., 5 or 10 mM), the aglycemia-induced
      decrease in [Ca(2+)](o) declined, indicating that less Ca(2+) left the
      extracellular space to enter an intracellular compartment. These results indicate
      that the role of [Ca(2+)], and divalent cations in general, during aglycemia is
      complex. While extracellular Ca(2+) was required for irreversible aglycemic
      injury to occur, higher levels of [Ca(2+)] or [Mg(2+)] increased the latency to
      CAP failure and improved the extent of recovery, apparently by limiting Ca(2+)
      influx. These effects are theorized to be mediated by divalent cation screening.

PMID- 12205152
TI  - Mutability of bifunctional thigh muscle activity in pedaling due to contralateral
      leg force generation.
AB  - Locomotion requires uninterrupted transitions between limb extension and flexion.
      The role of contralateral sensorimotor signals in executing smooth transitions is
      little understood even though their participation is crucial to bipedal walking.
      However, elucidating neural interlimb coordinating mechanisms in human walking is
      difficult because changes to contralateral sensorimotor activity also affect the
      ipsilateral mechanics. Pedaling, conversely, is ideal for studying bilateral
      coordination because ipsilateral mechanics can be independently controlled. In
      pedaling, the anterior and posterior bifunctional thigh muscles develop needed
      anterior and posterior crank forces, respectively, to dominate the flexion-to
      extension and extension-to-flexion transitions. We hypothesized that
      contralateral sensorimotor activity substantially contributes to the appropriate
      activation of these bifunctional muscles during the limb transitions. Bilateral
      pedal forces and surface electromyograms (EMGs) from four thigh muscles were
      collected from 15 subjects who pedaled with their right leg against a right-crank
      servomotor, which emulated the mechanical load experienced in conventional two
      legged coupled-crank pedaling. In one pedaling session, the contralateral (left)
      leg pseudo-pedaled (i.e., EMG activity and pedal forces were pedaling-like, but
      pedal force was not allowed to affect crank rotation). In other sessions, the
      mechanically decoupled contralateral leg was first relaxed and then produced
      rhythmic isometric force trajectories during either leg flexion or one of the two
      limb transitions of the pedaling leg. With contralateral force production in the
      extension-to-flexion transition (predominantly by the hamstrings), rectus femoris
      activity and work output increased in the pedaling leg during its flexion-to
      extension transition, which occurs simultaneously with contralateral extension-to
      flexion in conventional pedaling. Similarly, with contralateral force production
      in the other transition (i.e., flexion-to-extension; predominantly by rectus
      femoris), hamstrings activity and work output increased in the pedaling leg
      during its extension-to-flexion transition. Therefore rhythmic isometric force
      generation in the contralateral leg supported the ongoing bifunctional muscle
      activity and resulting work output in the pedaling leg. The results suggest that
      neural interlimb coordinating mechanisms fine-tune bifunctional muscle activity
      in rhythmic lower-limb tasks to ensure limb flexion/extension transitions are
      executed successfully.

PMID- 12205153
TI  - Two types of nicotinic receptors mediate an excitation of neocortical layer I
      interneurons.
AB  - Nicotinic acetylcholine receptors are widely expressed in the neocortex but their
      functional roles remain largely unknown. Here we investigated the effect of
      nicotinic receptor activation on interneurons of layer I, which contains a high
      density of cholinergic fiber terminals. Ninety-seven of 101 neurons recorded in
      whole cell configuration in rat acute slices were excited by local pressure
      application of nicotinic agonists, acetylcholine (500 microM), 1,1-dimethyl-4
      phenyl-piperazinium (500 microM) or choline (10 mM). Biocytin labeling confirmed
      that our sample included different morphological types of layer I interneurons.
      The responses to nicotinic agonists persisted in presence of glutamate and
      muscarinic receptor antagonists and on further addition of Cd(2+) or
      tetrodotoxin, indicating that they were mediated by direct activation of
      postsynaptic nicotinic receptors. The kinetics of the currents and their
      sensitivity to nicotinic receptor antagonists, methyllycaconitine (1-10 nM) or
      dihydro-beta-erythroidine (500 nM), suggested that early and late components of
      the responses were mediated by alpha7 and non-alpha7 types of receptors. Both
      components had inwardly rectifying I-V curves, which differed when intracellular
      spermine was omitted. Single-cell RT-PCR experiments identified alpha4, alpha7,
      and beta2 as the predominantly expressed mRNAs, suggesting that the receptors
      consisted of alpha7 homomers and alpha4beta2 heteromers. Finally, selective
      excitation of layer I interneurons through activation of their nicotinic
      receptors resulted in a tetrodotoxin-sensitive increase of inhibitory synaptic
      currents recorded in nonpyramidal cells but not in pyramidal cells of layer
      II/III. These results suggest that acetylcholine released in layer I may induce a
      disinhibition of the cortical network through activation of nicotinic receptors
      expressed by layer I interneurons.

PMID- 12205154
TI  - Synaptic precedence during synapse formation between reciprocally connected
      neurons involves transmitter-receptor interactions and AA metabolites.
AB  - The cellular mechanisms that determine specificity of synaptic connections
      between mutually connected neurons in the nervous system have not yet been fully
      examined in vertebrate and invertebrate species. Here we report on a novel form
      of synaptic interaction during early stages of synapse formation between
      reciprocally connected Lymnaea neurons. Specifically, using soma-soma synapses
      between an identified dopaminergic neuron (also known as the giant dopamine
      cell), right pedal dorsal 1 (RPeD1), and a FMRFamidergic neuron, visceral dorsal
      4 (VD4), we demonstrate that although reciprocal inhibitory synapses re-form
      between the somata after 24-36 h of pairing, VD4 is, however, the first cell to
      establish synaptic contacts with RPeD1 (within 12-18 h). We show that VD4
      "captures" RPeD1 first as a postsynaptic cell by suppressing its transmitter
      secretory machinery during early stages of cell-cell pairing. The VD4-induced
      suppression of transmitter release from RPeD1 was transient, and it required
      transcription and de novo protein synthesis dependent step in VD4 but not in
      RPeD1. The VD4-induced effects on RPeD1 were mimicked by a FMRFamide-like
      peptide. Perturbation of FMRFamide-activated metabolites of the arachidonic acid
      pathway in RPeD1 not only prevented FMRFamide-induced suppression of transmitter
      release from the giant dopamine cell but also shifted the synaptic balance in
      favor of RPeD1, thus making it the first cell to begin synaptic transmission with
      VD4 within 12-18 h. A single RPeD1 that had developed dopamine secretory
      capabilities overnight and was subsequently paired with VD4 for 12-18 h was,
      however, immune to VD4-induced suppression of transmitter release. Under these
      experimental conditions, both cells developed mutual inhibitory synapses
      concurrently. Taken together, our data provide evidence for novel synaptic
      interaction between reciprocally connected neurons and underscore the importance
      of transmitter-receptor interplay in regulating the timing of synapse formation
      in the nervous system.

PMID- 12205155
TI  - An index of topographic normality in rat somatosensory cortex: application to a
      sciatic nerve crush model.
AB  - Previous studies have demonstrated that peripheral denervation of the skin is
      reflected in the CNS as a reorganization of somatotopic representations. In cases
      in which peripheral nerve regeneration occurs there is a gradual reactivation of
      cortex by novel receptive fields that is reversed as regenerated nerves
      reestablish connections with the original skin surface. Functional recovery
      appears to depend on the pattern in which somatotopic organization in the cortex
      is reestablished. The relationship between functional recovery and cortical
      topography is not precise, however, since the descriptions of postinjury
      representations in the cortex have been largely descriptive and not quantitative.
      The purpose of this study was to derive an index to quantify deviations from
      normal somatotopic organization in the somatosensory cortex. Multiunit recordings
      of cutaneous representations in the somatosensory cortex (S1) of the rat were
      defined using Semmes-Weinstein monofilaments to stimulate the skin over the
      distal hindlimb of the rat 2 and 4 months after a sciatic nerve crush. To derive
      a sensitive index of topography, the sciatic nerve crush was selected as the
      injury model since nerve regeneration following crush injuries has been reported
      to reinstate preinjury cortical topography. Group comparisons were made with an
      intact control group. The results show that there were subtle, but significant
      differences in topography between rats with a regenerated sciatic nerve and
      normal rats. In addition, average thresholds for evoking cortical responses were
      higher than normal (but within normal range) 2 and 4 months after the crush.
      These results demonstrate that the index of topography derived for this study can
      reveal deviations that may not be distinguishable from normal topography when
      based on qualitative descriptions.

PMID- 12205156
TI  - Calcium-dependent regulation of cholinergic cell phenotype in the hypothalamus in
      vitro.
AB  - Glutamate is a major fast excitatory neurotransmitter in the CNS including the
      hypothalamus. Our previous experiments in hypothalamic neuronal cultures showed
      that a long-term decrease in glutamate excitation upregulates ACh excitatory
      transmission. Data suggested that in the absence of glutamate activity in the
      hypothalamus in vitro, ACh becomes the major excitatory neurotransmitter and
      supports the excitation/inhibition balance. Here, using neuronal cultures, fura-2
      Ca(2+) digital imaging, and immunocytochemistry, we studied the mechanisms of
      regulation of cholinergic properties in hypothalamic neurons. No ACh-dependent
      activity and a low number (0.5%) of cholinergic neurons were detected in control
      hypothalamic cultures. A chronic (2 wk) inactivation of N-methyl-D-aspartate
      (NMDA) ionotropic glutamate receptors, L-type voltage-gated Ca(2+) channels,
      calmodulin, Ca(2+)/calmodulin-dependent protein kinases II/IV (CaMK II/IV), or
      protein kinase C (PKC) increased the number of cholinergic neurons (to 15-24%)
      and induced ACh activity (in 40-60% of cells). Additionally, ACh activity and an
      increased number of cholinergic neurons were detected in hypothalamic cultures 2
      wk after a short-term (30 min) pretreatment with bis-(o-aminophenoxy)-N,N,N',N'
      tetraacetic acid tetrakis(acetoxy-methyl) ester (BAPTA AM; 2.5 microM), a
      membrane permeable Ca(2+)-chelating agent that blocks cytoplasmic Ca(2+)
      fluctuations. An increase in the number of cholinergic neurons following a
      chronic NMDA receptor blockade was likely due to the induction of cholinergic
      phenotypic properties in postmitotic noncholinergic neurons, as determined using
      5-bromo-2'-deoxyuridine (BrdU) labeling. In contrast, a chronic inactivation of
      non-NMDA glutamate receptors or cGMP-dependent protein kinase had little effect
      on the expression of ACh properties. The data suggest that Ca(2+), at normal
      intracellular concentrations, tonically suppresses the development of cholinergic
      properties in hypothalamic neurons. However, a decrease in Ca(2+) influx into
      cells (through NMDA receptors or L-type Ca(2+) channels), inactivation of
      intracellular Ca(2+) fluctuations, or downregulation of Ca(2+)-dependent signal
      transduction pathways (CaMK II/IV and PKC) remove the tonic inhibition and
      trigger the development of cholinergic phenotype in some hypothalamic neurons. An
      increase in excitatory ACh transmission may represent a novel form of neuronal
      plasticity that regulates the activity and excitability of neurons during a
      decrease in glutamate excitation. This type of plasticity has apparent region
      specific character and is not expressed in the cortex in vitro; neither increase
      in ACh activity nor change in the number of cholinergic neurons were detected in
      cortical cultures under all experimental conditions.

PMID- 12205157
TI  - Contrast-dependent changes in spatial frequency tuning of macaque V1 neurons:
      effects of a changing receptive field size.
AB  - Previous studies on single neurons in primary visual cortex have reported that
      selectivity for orientation and spatial frequency tuning do not change with
      stimulus contrast. The prevailing hypothesis is that contrast scales the response
      magnitude but does not differentially affect particular stimuli. Models where
      responses are normalized over contrast to maintain constant tuning for parameters
      such as orientation and spatial frequency have been proposed to explain these
      results. However, our results indicate that a fundamental property of receptive
      field organization, spatial summation, is not contrast invariant. We examined the
      spatial frequency tuning of cells that show contrast-dependent changes in spatial
      summation and have found that spatial frequency selectivity also depends on
      stimulus contrast. These results indicate that contrast changes in the spatial
      frequency tuning curves result from spatial reorganization of the receptive
      field.

PMID- 12205158
TI  - PACAP potentiates L-type calcium channel conductance in suprachiasmatic nucleus
      neurons by activating the MAPK pathway.
AB  - The endogenous pacemaker activity of the suprachiasmatic nuclei (SCN; the master
      clock in mammals) is regulated by photic information relayed from the retina to
      the SCN via the retinohypothalamic tract (RHT). Recent work has revealed that
      glutamate and pituitary adenylate cyclase-activating polypeptide (PACAP) are
      stored in RHT nerve terminals and function in a coordinated manner to regulate
      clock timing. To address this interaction on a cellular level, Fura-2 Ca(2+)
      digital imaging was employed and the effects of PACAP on glutamate evoked Ca(2+)
      transients in SCN neurons were examined. Pretreatment of SCN neurons with PACAP
      markedly potentiated Ca(2+) transients elicited by both exogenous glutamate
      application and synaptically released glutamate. Many neurons became responsive
      to glutamate only after PACAP administration, suggesting that PACAP sets the
      lower concentration threshold required for glutamate to initiate a robust rise in
      postsynaptic cytosolic Ca(2+). Facilitation of glutamate-induced Ca(2+)
      transients was inhibited by nimodipine, indicating that PACAP potentiates L-type
      Ca(2+) channel activity. The modulatory actions of PACAP were inhibited by
      antagonizing signaling via the p42/44 mitogen-activated protein kinase (MAPK)
      signal transduction cascade. Immunocytochemistry and Western analysis confirmed
      that PACAP stimulates MAPK activity at doses and time points shown to potentiate
      Ca(2+) influx. Down-regulation of protein kinase C (PKC) with the phorbol ester
      12-O-tetradecanoyl phorbol 13-acetate (TPA) or PKC inhibition with
      bisindolylmaleimide attenuated the actions of PACAP, indicating that PKC also
      couples PACAP to potentiation of depolarization-induced Ca(2+) transients. The
      data presented here identify potentially important mechanisms by which PACAP
      regulates SCN physiology.

PMID- 12205159
TI  - Acute topical application of tumor necrosis factor alpha evokes protein kinase A
      dependent responses in rat sensory neurons.
AB  - Local perfusion of the dorsal root ganglion (DRG) with tumor necrosis factor
      alpha (TNF-alpha) in rats induces cutaneous hypersensitivity to mechanical
      stimuli. Thus we investigated the cellular mechanisms of TNF-alpha-induced
      mechanical hyperalgesia. The L(4) and L(5) DRGs with the sciatic nerves attached
      were excised from rats for in vitro dorsal root microfilament recording. After
      baseline recording for 15 min, TNF-alpha (0.001, 0.01, 0.1, or 1 ng/ml) was
      applied to the DRG for 15 min, followed by washout for at least 30 min.
      Alternatively, H-89 or Rp-cAMPS, two specific cAMP-dependent protein kinase (PKA)
      inhibitors, was added to the perfusion solution for 15 min prior to TNF-alpha
      application. TNF-alpha (1 ng/ml) induced neuronal discharges in 67% (14/21) of C
      fibers and 27% (4/15) of Abeta fibers when applied topically to the DRG. Acute
      TNF-alpha application not only evoked discharges in silent fibers, but also
      enhanced ongoing activity of spontaneously active fibers and increased neuronal
      sensitivity to electrical stimulation of the peripheral nerves. H-89 (10 microM)
      and Rp-cAMPS (100 microM) each completely blocked the TNF-alpha-evoked response
      in most C and Abeta fibers tested but did not affect fiber conductivity. Our
      results demonstrates that exogenous inflammatory cytokines such as TNF-alpha can
      elicit a PKA-dependent response in sensory neurons and thus strongly suggest that
      endogenous TNF-alpha may contribute to the development of certain pathological
      pain states.

PMID- 12205160
TI  - Increased sensitivity of sensory neurons to tumor necrosis factor alpha in rats
      with chronic compression of the lumbar ganglia.
AB  - Proinflammatory cytokines may sensitize primary sensory neurons and facilitate
      development of neuropathic pain processes after peripheral nerve injury. The goal
      of this study was to determine whether responses of dorsal root ganglion (DRG)
      neurons to exogenous tumor necrosis factor alpha (TNF-alpha) are altered in a
      chronically compressed DRG (CCD) injury model. Extracellular recordings from
      teased dorsal root microfilaments demonstrated that acute topical application of
      TNF-alpha to the DRG for 15 min evoked C- and Abeta-fiber responses in both
      normal and CCD rats. However, the response latency was significantly shorter, and
      the peak discharge rate was higher, in CCD fibers than in normal fibers.
      Intracellular recordings from small- and large-sized neurons showed that TNF
      alpha induced greater depolarization and greater decrease in rheobase in CCD
      neurons than in normal neurons. The proportion of both small- and large-sized
      neurons that were responsive to TNF-alpha increased significantly after CCD
      injury. Furthermore, TNF-alpha altered the discharge patterns of large,
      spontaneously active neurons in addition to enhancing their discharge rates.
      However, the depolarization caused by TNF-alpha in such neurons was minor (<2
      mV). Inflammatory cytokines such as TNF-alpha increased the sensitivity of
      sensory neurons in normal and CCD rats. The CCD injury itself, on the other hand,
      increased neuronal responses to inflammatory cytokines.

PMID- 12205161
TI  - Somatosensory processing in the human inferior prefrontal cortex.
AB  - Three inferior prefrontal regions in the monkey receive afferents from
      somatosensory cortices: the orbitofrontal cortex (OFC), the ventral area of the
      principal sulcus, and the anterior frontal operculum. To determine whether these
      areas show responses to tactile stimuli in humans, we examined data from an
      ongoing series of PET studies of somatosensory processing. Unlike previous work
      showing ventral frontal activity to hedonic (pleasant/unpleasant) sensory
      stimulation, the tactile stimuli used in these studies had a neutral hedonic
      valence. Our data provide evidence for at least two discrete ventral frontal
      brain regions responsive to somatosensory stimulation: 1) the posterior inferior
      frontal gyrus (IFG) and adjacent anterior frontal operculum, and 2) the OFC. The
      former region (posterior IFG/anterior frontal operculum) may have a more specific
      role in attending to tactile stimuli.

PMID- 12205162
TI  - GAT-1 and reversible GABA transport in Bergmann glia in slices.
AB  - Although glial GABA uptake and release have been studied in vitro, GABA
      transporters (GATs) have not been characterized in glia in slices. Whole cell
      patch-clamp recordings were obtained from Bergmann glia in rat cerebellar slices
      to characterize carrier-mediated GABA influx and efflux. GABA induced inward
      currents at -70 mV that could be pharmacologically separated into GABA(A)
      receptor and GAT currents. In the presence of GABA(A/B/C) receptor blockers, mean
      GABA-induced currents measured -48 pA at -70 mV, were inwardly rectifying between
      -70 and +50 mV, were inhibited by external Na(+) removal, and were diminished by
      reduction of external Cl(-). Nontransportable blockers of GAT-1 (SKF89976-A and
      NNC-711) and a transportable blocker of all the GAT subtypes (nipecotic acid)
      reversibly reduced GABA-induced transport currents by 68 and 100%, respectively.
      A blocker of BGT-1 (betaine) had no effect. SKF89976-A and NNC-711 also
      suppressed baseline inward currents that likely result from tonic GAT activation
      by background GABA. The substrate agonists, nipecotic acid and beta-alanine but
      not betaine, induced voltage- and Na(+)-dependent currents. With Na(+) and GABA
      inside the patch pipette or intracellular GABA perfusion during the recording,
      SKF89976-A blocked baseline outward currents that activated at -60 mV and
      increased with more depolarized potentials. This carrier-mediated GABA efflux
      induced a local accumulation of extracellular GABA detected by GABA(A) receptor
      activation on the recorded cell. Overall, these results indicate that Bergmann
      glia express GAT-1 that are activated by ambient GABA. In addition, GAT-1 in glia
      can work in reverse and release sufficient GABA to activate nearby GABA
      receptors.

PMID- 12205163
TI  - Differential processing patterns of motor information via striatopallidal and
      striatonigral projections.
AB  - The functional loop linking the frontal lobe and the basal ganglia plays an
      important role in the control of motor behaviors. To delineate the principal
      features of motor information processing in the cortico-basal ganglia loop, the
      present study aimed at investigating how corticostriatal inputs from the primary
      motor cortex (MI) and the supplementary motor area (SMA) are transposed onto the
      pallidal complex and the substantia nigra. In macaque monkeys, stimulating
      electrodes were chronically implanted into identified forelimb representations of
      the MI and SMA. Subsequently, the distribution of neurons exhibiting orthodromic
      responses was examined in the caudal putamen to demarcate striatal zones
      receiving inputs separately or confluently from the MI and SMA. Finally,
      anterograde double labeling was performed by paired injections of tracers into
      two of three identified zones: the MI-recipient zone, SMA-recipient zone, and the
      convergent zone. Data have revealed that inputs from the MI-recipient and SMA
      recipient striatal zones were substantially segregated in the pallidal complex
      and that those from the convergent zone were distributed to fill in blanks made
      by terminal bands derived from the MI and SMA. On the other hand, striatonigral
      inputs from the SMA-recipient and convergent zones of the putamen largely
      overlapped, while the input from the MI-recipient zone was minimal. The present
      results clearly indicate that the mode to process corticostriatal motor
      information through the striatopallidal and striatonigral projections is target
      dependent, such that the parallel versus convergent rules govern the arrangement
      of striatopallidal or striatonigral inputs, respectively.

PMID- 12205164
TI  - Sound repetition rate in the human auditory pathway: representations in the
      waveshape and amplitude of fMRI activation.
AB  - Sound repetition rate plays an important role in stream segregation, temporal
      pattern recognition, and the perception of successive sounds as either distinct
      or fused. This study was aimed at elucidating the neural coding of repetition
      rate and its perceptual correlates. We investigated the representations of rate
      in the auditory pathway of human listeners using functional magnetic resonance
      imaging (fMRI), an indicator of population neural activity. Stimuli were trains
      of noise bursts presented at rates ranging from low (1-2/s; each burst is
      perceptually distinct) to high (35/s; individual bursts are not distinguishable).
      There was a systematic change in the form of fMRI response rate-dependencies from
      midbrain to thalamus to cortex. In the inferior colliculus, response amplitude
      increased with increasing rate while response waveshape remained unchanged and
      sustained. In the medial geniculate body, increasing rate produced an increase in
      amplitude and a moderate change in waveshape at higher rates (from sustained to
      one showing a moderate peak just after train onset). In auditory cortex (Heschl's
      gyrus and the superior temporal gyrus), amplitude changed somewhat with rate, but
      a far more striking change occurred in response waveshape-low rates elicited a
      sustained response, whereas high rates elicited an unusual phasic response that
      included prominent peaks just after train onset and offset. The shift in cortical
      response waveshape from sustained to phasic with increasing rate corresponds to a
      perceptual shift from individually resolved bursts to fused bursts forming a
      continuous (but modulated) percept. Thus at high rates, a train forms a single
      perceptual "event," the onset and offset of which are delimited by the on and off
      peaks of phasic cortical responses. While auditory cortex showed a clear,
      qualitative correlation between perception and response waveshape, the medial
      geniculate body showed less correlation (since there was less change in waveshape
      with rate), and the inferior colliculus showed no correlation at all. Overall,
      our results suggest a population neural representation of the beginning and the
      end of distinct perceptual events that is weak or absent in the inferior
      colliculus, begins to emerge in the medial geniculate body, and is robust in
      auditory cortex.

PMID- 12205165
TI  - Direct comparison of neural systems mediating conscious and unconscious skill
      learning.
AB  - Procedural learning, such as perceptual-motor sequence learning, has been
      suggested to be an obligatory consequence of practiced performance and to reflect
      adaptive plasticity in the neural systems mediating performance. Prior
      neuroimaging studies, however, have found that sequence learning accompanied with
      awareness (declarative learning) of the sequence activates entirely different
      brain regions than learning without awareness of the sequence (procedural
      learning). Functional neuroimaging was used to assess whether declarative
      sequence learning prevents procedural learning in the brain. Awareness of the
      sequence was controlled by changing the color of the stimuli to match or differ
      from the color used for random sequences. This allowed direct comparison of brain
      activation associated with procedural and declarative memory for an identical
      sequence. Activation occurred in a common neural network whether initial learning
      had occurred with or without awareness of the sequence, and whether subjects were
      aware or not aware of the sequence during performance. There was widespread
      additional activation associated with awareness of the sequence. This supports
      the view that some types of unconscious procedural learning occurs in the brain
      whether or not it is accompanied by conscious declarative knowledge.

PMID- 12205166
TI  - Involvement of calcium in rhythmic activity induced by disinhibition in cultured
      spinal cord networks.
AB  - Disinhibition of rat spinal networks induces a spontaneous rhythmic bursting
      activity. The major mechanisms involved in the generation of such a bursting are
      intrinsic neuronal firing of a subpopulation of interneurons, recruitment of the
      network by recurrent excitation, and autoregulation of neuronal excitability. We
      have combined whole cell recording with calcium imaging and flash photolysis of
      caged-calcium to investigate the contribution of [Ca(2+)](i) to rhythmogenesis.
      We found that calcium mainly enters the neurons through voltage-activated calcium
      channels and N-methyl-D-aspartate (NMDA) channels as a consequence of the
      depolarization during the bursts. However, [Ca(2+)](i) could neither predict the
      start nor the termination of bursts and is therefore not critically involved in
      rhythmogenesis. Also calcium-induced calcium release is not involved as a primary
      mechanism in bursting activity. From these findings, we conclude that in the
      rhythmic activity induced by disinhibition of spinal cord networks, the loading
      of the cells with calcium is a consequence of bursting and does not functionally
      contribute to rhythm generation.

PMID- 12205167
TI  - Postnatal development of rat hippocampal gamma rhythm in vivo.
AB  - Network oscillations in the gamma-frequency band (20-100 Hz) may have a central
      role in the timing and coordination of neural activity in the adult brain, yet
      their appearance in the course of development has remained unexplored. Moreover,
      electroencephalogram (EEG)-based classification of the vigilance states [active
      sleep (AS), quiet sleep (QS), or awake (W)] has been thought to be possible only
      after the second postnatal week. We now report the presence of spontaneous
      hippocampal gamma oscillations in the area CA3 of freely moving rats at postnatal
      days (P) 5-10. Initially, at P5, the gamma oscillations were seen in time
      frequency analyses of intrahippocampal EEG recordings as brief (<500 ms) bursts
      at 20-30 Hz. The early gamma rhythmicity was most pronounced during periods of AS
      but was occasionally detected also during QS. Toward P10, the gamma oscillations
      gained amplitude and extended also to higher (<or=60 Hz) frequencies. In
      parallel, the gamma oscillations were progressively more and more confined to AS.
      To further consolidate these findings, we compared amplitude spectra averaged
      within the behavioral categories. AS was characterized by the appearances of
      gamma (20-30 Hz) and theta (3-5 Hz) peaks at P6 and at P8, respectively. QS, on
      the other hand, had considerably smoother amplitude distributions between 1 and
      100 Hz for P5-P10, with no peaks in gamma or theta bands. Hippocampal gamma
      rhythm thus seems to hallmark early AS. Our data provide the first in vivo
      evidence for both the presence and the behavioral correlate of spontaneous gamma
      oscillations in the newborn rat.

PMID- 12205168
TI  - Differential involvement of Ca(2+) channels in survival and neurite outgrowth of
      cultured embryonic cockroach brain neurons.
AB  - The contribution of voltage-gated calcium channels (VGCC) to the development of
      cultured embryonic cockroach brain neurons was assessed using pharmacological
      agents. VGCC currents were recorded using the patch-clamp technique and were
      found to be blocked dose-dependently by micromolar concentrations of mibefradil.
      The activation and inactivation properties of the calcium channels enable a
      sizeable calcium current to flow at rest (about -30 and -20 mV in high-potassium
      culture media). As expected, the cytoplasmic-free calcium concentration was found
      to rise when the extracellular potassium concentration was raised from 3 to 15
      and 30 mM. The effects of VGCC blockers and calcium chelators were different in
      fresh and in mature cultures in which the neurons were connected to each other to
      form a defined network. In fresh cultures, the two non-selective VGCC blockers
      (verapamil and mibefradil) induced a dose-dependent cell death that was
      proportional to their blocking effect on I(Ba). This effect could not be
      prevented by addition of fetal calf serum to the culture medium. A similar effect
      was obtained using intra- or extracellular calcium chelating agents (10 microM
      BAPTA-AM or 10 mM EGTA). Quite unexpectedly, blockade of the P/Q-like (omega-Aga
      WA-sensitive) component of the calcium current by 500 nM of omega-AgaTx IVA had
      no lethal effect, suggesting that the corresponding channels are not involved in
      the survival mechanism. As expected from their lack of effect on I(Ba),
      isradipine, nifedipine, and omega-CgTx GVIA did not induce cell death. When the
      neurons started growing neurites, their sensitivity to calcium channel blockade
      by mibefradil decreased, indicating a correlation between neurite outgrowth and
      resistance to calcium depletion. In mature cultures, the neurons became resistant
      to mibefradil, verapamil, and BAPTA-AM. However, these agents, as well as omega
      AgaTx IVA, had a significant inhibitory effect on the increase in diameter of the
      connectives that linked adjacent clusters of neurons. This effect has been shown
      to result, in the case of mibefradil, from an inhibition of neurite outgrowth
      characterized by a significant reduction of the number of primary neurites and
      secondary branchings but not to a significant modification of the diameter of
      individual neurites. These results support the view that, as in vertebrates,
      calcium influx through VGCC plays an important role in survival and neurite
      outgrowth of cultured embryonic insect neurons. The differential contribution of
      the P/Q-like and R-like (omega-Aga WA-sensitive) calcium channels in these
      processes is discussed.

PMID- 12205169
TI  - Prehension movements in the macaque monkey: effects of object size and location.
AB  - Prehension movements were examined in freely behaving monkeys and compared with
      the well-known characteristics of human movements. The degree of independence of
      the components of movements (i.e., reaching and grasping) was investigated in
      animals trained to reach for and grasp three-dimensional objects. To this aim,
      the kinematics of prehension movements was recorded using an Optotrak system in
      two tasks. In one task, monkeys grasped a small or a large object (size task), in
      the other, they grasped an object of constant size placed at three different
      spatial locations (location task). We found that object size and its location
      affected both reaching and grasping. In particular, in the size task, we found
      that the maximum grip aperture strongly depended on the selection of the grip and
      not only on the size of an object. Our results also revealed that, in monkeys as
      well as in humans, the reaching parameters are highly sensitive to task-related
      constraints such as accuracy demands. The results of the location task showed a
      difference between rightward and leftward movements, a pattern of grip aperture
      that varied across animals, and a large degree of coordination between the two
      components. These findings argue against a strict postulate of independence
      between the visuo-motor channels, favoring instead the idea of variable degrees
      of coordination between the reach and grasp components depending on the task
      demands. Finally, this work emphasizes the relevance of studying monkey's
      prehension movements as a useful step to the understanding of visuo-motor control
      in humans.

PMID- 12205170
TI  - BOLD fMRI identifies limbic, paralimbic, and cerebellar activation during air
      hunger.
AB  - Air hunger (uncomfortable urge to breathe) is a component of dyspnea (shortness
      of breath). Three human H(2)(15)O positron emission tomography (PET) studies have
      identified activation of phylogenetically ancient structures in limbic and
      paralimbic regions during dyspnea. Other studies have shown activation of these
      structures during other sensations that alert the organism to urgent homeostatic
      imbalance: pain, thirst, and hunger for food. We employed blood oxygen level
      dependent (BOLD) functional magnetic resonance imaging (fMRI) to examine
      activation during air hunger. fMRI conferred several advantages over PET:
      enhanced signal-to-noise, greater spatial resolution, and lack of ionizing
      radiation, enabling a greater number of trials in each subject. Six healthy men
      and women were mechanically ventilated at 12-14 breaths/min. The primary
      experiment was conducted at mean end-tidal PCO(2) of 41 Torr. Moderate to severe
      air hunger was evoked during 42-s epochs of lower tidal volume (mean = 0.75 L).
      Subjects described the sensation as "like breath-hold," "urge to breathe," and
      "starved for air." In the baseline condition, air hunger was consistently
      relieved by epochs of higher tidal volume (mean = 1.47 L). A control experiment
      in the same subjects under a background of mild hypocapnia (mean end-tidal PCO(2)
      = 33 Torr) employed similar tidal volumes but did not evoke air hunger,
      controlling for stimulus variables not related to dyspnea. During each
      experiment, we maintained constant end-tidal PCO(2) and PO(2) to avoid systematic
      changes in global cerebral blood flow. Whole-brain images were acquired every 5 s
      (T2*, 56 slices, voxel resolution 3 x 3 x 3 mm). Activations associated with air
      hunger were determined using voxel-based interaction analysis of covariance that
      compared data between primary and control experiments (SPM99). We detected
      activations not seen in the earlier PET study using a similar air hunger stimulus
      (Banzett et al. 2000). Limbic and paralimbic loci activated in the present study
      were within anterior insula (seen in all 3 published studies of dyspnea),
      anterior cingulate, operculum, cerebellum, amygdala, thalamus, and basal ganglia.
      Elements of frontoparietal attentional networks were also identified. The
      consistency of anterior insular activation across subjects in this study and
      across published studies suggests that the insula is essential to dyspnea
      perception, although present data suggest that the insula acts in concert with a
      larger neural network.

PMID- 12205171
TI  - Prostaglandin E(2) modulates TTX-R I(Na) in rat colonic sensory neurons.
AB  - This study was performed to determine the impact of the inflammatory mediator
      prostaglandin E(2) (PGE(2)) on the biophysical properties of tetrodotoxin
      resistant voltage-gated Na(+) currents (TTX-R I(Na)) in colonic dorsal root
      ganglion (DRG) neurons. TTX-R I(Na) was studied in DRG neurons from thoracolumbar
      (TL: T(13)-L(2)) and lumbosacral (LS: L(6)-S(2)) DRG retrogradely labeled
      following the injection of DiIC(18) (DiI) into the wall of the descending colon
      of adult male rats. TTX-R I(Na) in colonic DRG neurons had a high threshold for
      activation [V(0.5) of conductance-voltage (G-V) curve = -3.1 +/- 1.0 (SE) mV] and
      steady-state availability (V(0.5) for H-infinity curve = -18.4 +/- 1.4 mV), was
      slowly inactivating (10.6 +/- 1.4 ms at 0 mV), and recovered rapidly from
      inactivation (83.5 +/- 5.0% of the current recovered with a time constant of 1.3
      +/- 0.1 ms at -80 mV). TTX-R I(Na) was present in every colonic DRG neuron
      studied (n = 62). PGE(2) induced a rapid (<15 s) increase in TTX-R I(Na) that was
      associated with a hyperpolarizing shift in the G-V curve (3.4 +/- 0.7 mV), an
      increase in the rate of inactivation (4.21 +/- 0.7 ms at 0 mV), and no change in
      steady-state availability. There was no statistically significant difference (P >
      0.05) between TL and LS colonic DRG neurons with respect to the biophysical
      properties of TTX-R I(Na), the current density or the magnitude of PGE(2)-induced
      changes in the current. However, both the proportion of TL and LS neurons in
      which TTX-R I(Na) was modulated by PGE(2) (16 of 16 TL neurons and 12 of 14 LS
      neurons) as well as the magnitude of PGE(2)-induced changes in the current were
      significantly larger in colonic DRG neurons than in the total population of DRG
      neurons. These results suggest that changes in nociceptive processing associated
      with inflammation of the colon does not reflect differences between TL and LS
      neurons with respect to the properties of TTX-R I(Na), distribution of current,
      or magnitude of inflammatory mediator-induced changes in the current. However,
      these results do suggest modulation of TTX-R I(Na) in colonic afferents is an
      underlying mechanism of hyperalgesia and pain associated with inflammation of the
      colon and that this current constitutes a novel target for therapeutic relief of
      visceral inflammatory pain.

PMID- 12205172
TI  - Optical imaging of long-lasting depolarization on burst stimulation in area CA1
      of rat hippocampal slices.
AB  - Postsynaptic depolarization of dendrites paired with spike generation at the soma
      is considered to be a central mechanism of long-term potentiation (LTP) induction
      and a prime example of a Hebbian synapse. This pairing, however, has never been
      actually demonstrated on tetanic stimulation. Optical imaging of neural activity
      with a voltage-sensitive dye (VSD) is one potentially suitable method for
      examining this pairing. It is possible with optical recording to examine
      simultaneously the excitation of postsynaptic neurons at multiple sites. Thus the
      pairing of spike generation at the soma and dendritic depolarization can be
      examined with population level optical recording in highly laminar structures
      such as the hippocampal slice preparation. For example, one can correlate the
      optical signals obtained from cell layers with the activity of the soma, and,
      similarly, optical signals from stratum radiatum can be correlated with the
      activity of the apical dendrite, even though one cannot calibrate the optical
      signals in terms of actual membrane potential. Using the VSD
      aminonaphthylethenylpyridinium in rat hippocampal slices, we aimed to examine the
      pairing. Standard tetanic stimulation (100 Hz, 1 s) that elicited LTP in the
      field excitatory postsynaptic potential (fEPSP) resulted in a long-lasting
      depolarizing optical signal (about 2 s) that spread progressively along the known
      input pathway of CA1. The time course of this long-lasting depolarization was
      similar to that recorded intracellularly and to that reflected in the fEPSP. The
      long-lasting depolarization was insensitive to D,L-2-amino-5-phosphonovaleric
      acid (D,L-APV, 50 microM), but D,L-APV inhibited the induction of LTP; this
      allowed us to increase the signal-to-noise ratio of the optical signal by
      averaging several trials. Using this improved optical signal, we confirmed that
      postsynaptic cells practically "missed" spikes during tetanic stimulation in most
      parts of CA1, which had been suggested in the intracellular recordings.
      Intracellular recordings revealed a 23% reduction in input resistance, which
      might explain the failed spike generation at the soma via shunting. A steep
      spatial convergence of the depolarization along the transverse axis of area CA1
      was observed. In contrast to the response resulting from a standard 100-Hz
      tetanus, broader activation, and paired depolarization with somatic spikes was
      observed on theta-burst stimulation. Overall we concluded that postsynaptic spike
      generation, at least in synchronous form, has less effect on LTP induction with
      standard tetanic stimulation, while theta-burst tetanic stimulation can elicit
      pairing of dendritic depolarization and somatic discharge.

PMID- 12205173
TI  - Sources of signal-dependent noise during isometric force production.
AB  - It has been proposed that the invariant kinematics observed during goal-directed
      movements result from reducing the consequences of signal-dependent noise (SDN)
      on motor output. The purpose of this study was to investigate the presence of SDN
      during isometric force production and determine how central and peripheral
      components contribute to this feature of motor control. Peripheral and central
      components were distinguished experimentally by comparing voluntary contractions
      to those elicited by electrical stimulation of the extensor pollicis longus
      muscle. To determine other factors of motor-unit physiology that may contribute
      to SDN, a model was constructed and its output compared with the empirical data.
      SDN was evident in voluntary isometric contractions as a linear scaling of force
      variability (SD) with respect to the mean force level. However, during
      electrically stimulated contractions to the same force levels, the variability
      remained constant over the same range of mean forces. When the subjects were
      asked to combine voluntary with stimulation-induced contractions, the linear
      scaling relationship between the SD and mean force returned. The modeling results
      highlight that much of the basic physiological organization of the motor-unit
      pool, such as range of twitch amplitudes and range of recruitment thresholds,
      biases force output to exhibit linearly scaled SDN. This is in contrast to the
      square root scaling of variability with mean force present in any individual
      motor-unit of the pool. Orderly recruitment by twitch amplitude was a necessary
      condition for producing linearly scaled SDN. Surprisingly, the scaling of SDN was
      independent of the variability of motoneuron firing and therefore by inference,
      independent of presynaptic noise in the motor command. We conclude that the
      linear scaling of SDN during voluntary isometric contractions is a natural by
      product of the organization of the motor-unit pool that does not depend on signal
      dependent noise in the motor command. Synaptic noise in the motor command and
      common drive, which give rise to the variability and synchronization of
      motoneuron spiking, determine the magnitude of the force variability at a given
      level of mean force output.

PMID- 12205174
TI  - Optical imaging of intrinsic signals in ferret auditory cortex: responses to
      narrowband sound stimuli.
AB  - This paper describes optical imaging of the auditory cortex in the anesthetized
      ferret, particularly addressing optimization of narrowband stimuli. The types of
      sound stimuli used were tone-pip trains and sinusoidal frequency and amplitude
      modulated (SFM and SAM) tones. By employing short illumination wavelengths (546
      nm), we have successfully characterized the tonotopic arrangement, in agreement
      with the well-established electrophysiological tonotopic maps of the ferret
      auditory primary field (AI). The magnitude of the optical signal increased with
      sound level, was maximal for a modulation frequency (MF) of 2-4 Hz, and was
      larger for tone-pip trains and SFM sounds than for SAM sounds. Accordingly, an
      optimal narrowband stimulus was defined. Thus optical imaging can be used
      successfully to obtain frequency maps in auditory cortex by an appropriate choice
      of stimulus parameters. In addition, background noise consisting of 0.1-Hz
      oscillations could be reduced by introduction of blood pressure enhancing drugs.
      The optical maps were largely independent of 1) the type of narrowband stimulus,
      2) the sound level, and 3) the MF. This stability of the optical maps was not
      predicted from the electrophysiological literature.

PMID- 12205175
TI  - Synchronization of Ca(2+) oscillations among primate LHRH neurons and nonneuronal
      cells in vitro.
AB  - Periodic release of luteinizing hormone-releasing hormone (LHRH) from the
      hypothalamus is essential for normal reproductive function. Pulsatile LHRH
      release appears to result from the synchronous activity of LHRH neurons. However,
      how the activity of these neurons is synchronized to release LHRH peptide in a
      pulsatile manner is unclear. Because there is little evidence of physical
      coupling among LHRH neurons in the hypothalamus, we hypothesized that the
      activity of LHRH neurons might be coordinated by indirect intercellular
      communication via intermediary (nonneural) cells rather than direct interneural
      coupling. In this study, we used an in vitro preparation of LHRH neurons derived
      from the olfactory placode of monkey embryos to assess whether nonneuronal cells,
      play a role in coordinating LHRH neuronal activity. We found that cultured LHRH
      neurons and nonneuronal cells both exhibit spontaneous oscillations in the
      concentration of intracellular Ca(2+) ([Ca(2+)](i)) at similar frequencies.
      Moreover, [Ca(2+)](i) oscillations in both types of cell were periodically
      synchronized. Synchronized [Ca(2+)](i) oscillations spread as intercellular
      Ca(2+) waves across fields of cells that included LHRH neurons and nonneuronal
      cells, although waves spread at a higher velocity among LHRH neurons. These
      results suggest that LHRH neurons and nonneuronal cells are functionally
      integrated and that nonneuronal cells could be involved in synchronizing the
      activity of the LHRH neurosecretory network.

PMID- 12205176
TI  - Subliminal messages in hippocampal pyramidal cells.

PMID- 12205177
TI  - Exercise and gene expression: physiological regulation of the human genome
      through physical activity.
AB  - The current human genome was moulded and refined through generations of time. We
      propose that the basic framework for physiologic gene regulation was selected
      during an era of obligatory physical activity, as the survival of our Late
      Palaeolithic (50 000-10 000 BC) ancestors depended on hunting and gathering. A
      sedentary lifestyle in such an environment probably meant elimination of that
      individual organism. The phenotype of the present day Homo sapiens genome is much
      different from that of our ancient ancestors, primarily as a consequence of
      expressing evolutionarily programmed Late Palaeolithic genes in an environment
      that is predominantly sedentary. In this sense, our current genome is maladapted,
      resulting in abnormal gene expression, which in turn frequently manifests itself
      as clinically overt disease. We speculate that some of these genes still play a
      role in survival by causing premature death from chronic diseases produced by
      physical inactivity. We also contend that the current scientific evidence
      supports the notion that disruptions in cellular homeostasis are diminished in
      magnitude in physically active individuals compared with sedentary individuals
      due to the natural selection of gene expression that supports the physically
      active lifestyle displayed by our ancestors. We speculate that genes evolved with
      the expectation of requiring a certain threshold of physical activity for normal
      physiologic gene expression, and thus habitual exercise in sedentary cultures
      restores perturbed homeostatic mechanisms towards the normal physiological range
      of the Palaeolithic Homo sapiens. This hypothesis allows us to ask the question
      of whether normal physiological values change as a result of becoming sedentary.
      In summary, in sedentary cultures, daily physical activity normalizes gene
      expression towards patterns established to maintain the survival in the Late
      Palaeolithic era.

PMID- 12205178
TI  - An external site controls closing of the epithelial Na+ channel ENaC.
AB  - Members of the ENaC/degenerin family of ion channels include the epithelial
      sodium channel (ENaC), acid-sensing ion channels (ASICs) and the nematode
      Caenorhabditis elegans degenerins. These channels are activated by a variety of
      stimuli such as ligands (ASICs) and mechanical forces (degenerins), or otherwise
      are constitutively active (ENaC). Despite their functional heterogeneity, these
      channels might share common basic mechanisms for gating. Mutations of a conserved
      residue in the extracellular loop, namely the 'degenerin site' activate all
      members of the ENaC/degenerin family. Chemical modification of a cysteine
      introduced in the degenerin site of rat ENaC (betaS518C) by the sulfhydryl
      reagents MTSET or MTSEA, results in a approximately 3-fold increase in the open
      probability. This effect is due to an 8-fold shortening of channel closed times
      and an increase in the number of long openings. In contrast to the intracellular
      gating domain in the N-terminus which is critical for channel opening, the intact
      extracellular degenerin site is necessary for normal channel closing, as
      illustrated by our observation that modification of betaS518C destabilises the
      channel closed state. The modification by the sulfhydryl reagents is state- and
      size-dependent consistent with a conformational change of the degenerin site
      during channel opening and closing. We propose that the intracellular and
      extracellular modulatory sites act on a common channel gate and control the
      activity of ENaC at the cell surface.

PMID- 12205179
TI  - The presence of Ca2+ channel beta subunit is required for mitogen-activated
      protein kinase (MAPK)-dependent modulation of alpha1B Ca2+ channels in COS-7
      cells.
AB  - In rat sensory neurones, voltage-dependent calcium channels (VDCCs), including
      the N-type, are tonically up-regulated via Ras/mitogen-activated protein kinase
      (MAPK) signalling. To determine whether VDCC beta subunit is involved in this
      process, the role of the four neuronal betas (beta1b, beta2a, beta3, beta4) in
      MAPK-dependent modulation of alpha1B (Ca(v)2.2, N-type) Ca(2+) channels has been
      examined in COS-7 cells. MAPK is exclusively activated by MAPK kinase (MEK), and
      here, acute application of a MEK-specific inhibitor UO126, significantly
      inhibited peak alpha1B Ca2+ channel current (I(max)) within a period of 5-10 min,
      regardless of which beta subunit was co-expressed (25-50 %, P < 0.01). With
      beta2a however, the percentage inhibition of I(max) was less than that observed
      with any other beta (ANOVA: F(3,34) = 6.48, P < 0.01). UO126 also caused a
      hyperpolarising shift (6 +/- 1 mV, P < 0.001) in the voltage dependence of beta2a
      current activation, such that inhibition occurred only at depolarised potentials
      (> +5 mV) whereas at more negative potentials the current amplitude was enhanced.
      A marked change in beta2a current kinetics, perceived either as decreased
      activation or increased inactivation, was also associated with UO126 application.
      A similar effect of UO126 on beta4 current kinetics was also observed. The beta2a
      specific effects of UO126 on current inhibition and voltage dependence of
      activation were abolished when alpha1B was co-expressed with de-palmitoylated
      beta2a(C3,4S), in which amino terminal cysteines 3 and 4 had been mutated to
      serines. In the absence of beta subunit, UO126 had no effect on alpha1B Ca2+
      channel current. Together, these data suggest an absolute requirement for beta in
      MAPK-dependent modulation of these channels. Since beta subunits vary both in
      their temporal expression and localisation within neurones, beta subunit
      dependent modulation of N-type Ca2+ channels via MAPK could provide an important
      new mechanism by which to fine-tune neurotransmitter release.

PMID- 12205180
TI  - Ca2+ current-gated focal and local Ca2+ release in rat atrial myocytes: evidence
      from rapid 2-D confocal imaging.
AB  - In atrial myocytes immunocytochemistry has shown two groups of ryanodine
      receptors (RyRs): those at the periphery colocalized with dihydropyridine
      receptors (DHPRs) and those at the cell interior not associated with DHPRs. The
      extent to which the two sets of RyRs are controlled by Ca2+ current (I(Ca)) or
      Ca2+ diffusion remains to be determined. Here, using rapid (240 Hz) two
      dimensional confocal Ca2+ imaging in rat atrial myocytes, we examine directly the
      role of I(Ca) on the two-dimensional patterns of local and focal Ca2+ releases.
      I(Ca) evoked peripheral Ca2+ release within 1-4 ms, causing a rapid monophasic
      local rise of Ca2+, which then propagated into the cell interior along sarcomeric
      lines (approximately 2 microm) with a velocity of approximately 230 microm s(-1),
      even though we found no evidence for organized t-tubules using di-8-ANEPPS
      staining. I(Ca)-triggered Ca2+ release in the cell centre, on the other hand, had
      both a rapid (12 ms) and slower delayed components (12-50 ms). The voltage
      dependence of peripheral Ca2+ release and the two components of central release
      was bell shaped, and the magnitude of each release component was linearly related
      to I(Ca). Premature termination (2-10 ms) of I(Ca) was equally effective in
      abbreviating both the peripheral and slow central Ca2+ release. High
      concentration of Ca2+ buffers (2-5 mM EGTA plus 1 mM fluo-3) completely abolished
      the I(Ca)-gated propagation wave and the slow delayed component of Ca2+ release,
      but had little or no effect on the rapid component of central release. The
      efficacy of I(Ca) to trigger Ca2+ release in periphery of the myocyte was
      approximately 5 times higher than in the centre, consistent with the smaller
      measured central Ca2+ release. The quantification of central Ca2+ release as a
      function of peripheral release suggests a cooperative gating mechanism(s) for
      central release. These findings indicate that both I(Ca) and diffusion of Ca2+
      from the peripheral sites contribute to the gating of Ca2+ release from central
      SR. How in fact the I(Ca)-dependent fast component of central release is
      activated remains to be determined.

PMID- 12205181
TI  - Discrete store-operated calcium influx into an intracellular compartment in
      rabbit arteriolar smooth muscle.
AB  - This study tested the hypothesis that store-operated channels (SOCs) exist as a
      discrete population of Ca2+ channels activated by depletion of intracellular
      Ca(2+) stores in cerebral arteriolar smooth muscle cells and explored their
      direct contractile function. Using the Ca2+ indicator fura-PE3 it was observed
      that depletion of sarcoplasmic reticulum (SR) Ca2+ by inhibition of SR Ca2+
      ATPase (SERCA) led to sustained elevation of [Ca2+]i that depended on
      extracellular Ca2+ and slightly enhanced Mn2+ entry. Enhanced background Ca2+
      influx did not explain the raised [Ca2+]i in response to SERCA inhibitors because
      it had marked gadolinium (Gd3+) sensitivity, which background pathways did not.
      Effects were not secondary to changes in membrane potential. Thus SR Ca2+
      depletion activated SOCs. Strikingly, SOC-mediated Ca2+ influx did not evoke
      constriction of the arterioles, which were in a resting state. This was despite
      the fura-PE3-indicated [Ca2+]i rise being greater than that evoked by 20 mM [K+]o
      (which did cause constriction). Release of endothelial vasodilators did not
      explain the absence of SOC-mediated constriction, nor did a change in Ca2+
      sensitivity of the contractile proteins. We suggest SOCs are a discrete subset of
      Ca2+ channels allowing Ca2+ influx into a 'non-contractile' compartment in
      cerebral arteriolar smooth muscle cells.

PMID- 12205182
TI  - Spatial segregation and interaction of calcium signalling mechanisms in rat
      hippocampal CA1 pyramidal neurons.
AB  - Postsynaptic [Ca2+]i increases result from Ca2+ entry through ligand-gated
      channels, entry through voltage-gated channels, or release from intracellular
      stores. We found that these sources have distinct spatial distributions in
      hippocampal CA1 pyramidal neurons. Large amplitude regenerative release of Ca2+
      from IP3-sensitive stores in the form of Ca2+ waves were found almost exclusively
      on the thick apical shaft. Smaller release events did not extend more than 15
      microm into the oblique dendrites. These synaptically activated regenerative
      waves initiated at points where the stimulated oblique dendrites branch from the
      apical shaft. In contrast, NMDA receptor-mediated increases were observed
      predominantly in oblique dendrites where spines are found at high density. These
      [Ca2+]i increases were typically more than eight times larger than [Ca2+]i from
      this source on the main aspiny apical shaft. Ca2+ entry through voltage-gated
      channels, activated by backpropagating action potentials, was detected at all
      dendritic locations. These mechanisms were not independent. Ca2+ entry through
      NMDA receptor channels or voltage-gated channels (as previously demonstrated)
      synergistically enhanced Ca2+ release generated by mGluR mobilization of IP3.

PMID- 12205183
TI  - Role of protein kinase C in light adaptation of molluscan microvillar
      photoreceptors.
AB  - The mechanisms by which Ca2+ regulates light adaptation in microvillar
      photoreceptors remain poorly understood. Protein kinase C (PKC) is a likely
      candidate, both because some sub-types are activated by Ca2+ and because of its
      association with the macromolecular 'light-transduction complex' in Drosophila.
      We investigated the possible role of PKC in the modulation of the light response
      in molluscan photoreceptors. Western blot analysis with isoform-specific
      antibodies revealed the presence of PKCalpha in retinal homogenates.
      Immunocytochemistry in isolated cell preparations confirmed PKCalpha localization
      in microvillar photoreceptors, preferentially confined to the light-sensing lobe.
      Light stimulation induced translocation of PKCalpha immunofluorescence to the
      photosensitive membrane, an effect that provides independent evidence for PKC
      activation by illumination; a similar outcome was observed after incubation with
      the phorbol ester PMA. Several chemically distinct activators of PKC, such as
      phorbol-12-myristate-13-acetate (PMA), (-)indolactam V and 1,2,-dioctanoyl-sn
      glycerol (DOG) inhibited the light response of voltage-clamped microvillar
      photoreceptors, but were ineffective in ciliary photoreceptors, in which light
      does not activate the G(q)/PLC cascade, nor elevates intracellular Ca2+.
      Pharmacological inhibition of PKC antagonized the desensitization produced by
      adapting lights and also caused a small, but consistent enhancement of basal
      sensitivity. These results strongly support the involvement of PKC activation in
      the light-dependent regulation of response sensitivity. However, unlike adapting
      background light or elevation of [Ca2+]i, PKC activators did not speed up the
      photoresponse, nor did PKC inhibitors antagonize the accelerating effects of
      background adaptation, suggesting that modulation of photoresponse time course
      may involve a separate Ca2+-dependent signal.

PMID- 12205184
TI  - Allosteric modulation of the mouse Kir6.2 channel by intracellular H+ and ATP.
AB  - The ATP-sensitive K+ (K(ATP)) channels are regulated by intracellular H+ in
      addition to ATP, ADP, and phospholipids. Here we show evidence for the
      interaction of H+ with ATP in regulating a cloned K(ATP) channel, i.e. Kir6.2
      expressed with and without the SUR1 subunit. Channel sensitivity to ATP decreases
      at acidic pH, while the pH sensitivity also drops in the presence of ATP. These
      effects are more evident in the presence of the SUR1 subunit. In the Kir6.2 +
      SUR1, the pH sensitivity is reduced by about 0.4 pH units with 100 microM ATP and
      0.6 pH units with 1 mM ATP, while a decrease in pH from 7.4 to 6.8 lowers the ATP
      sensitivity by about fourfold. The Kir6.2 + SUR1 currents are strongly activated
      at pH 5.9-6.5 even in the presence of 1 mM ATP. The modulations appear to take
      place at His175 and Lys185 that are involved in proton and ATP sensing,
      respectively. Mutation of His175 completely eliminates the pH effect on the ATP
      sensitivity. Similarly, the K185E mutant-channel loses the ATP-dependent
      modulation of the pH sensitivity. Thus, allosteric modulations of the cloned
      K(ATP) channel by ATP and H+ are demonstrated. Such a regulation allows protons
      to activate directly the K(ATP) channels and release channel inhibition by
      intracellular ATP; the pH effect is further enhanced with a decrease in ATP
      concentration as seen in several pathophysiological conditions.

PMID- 12205186
TI  - Modulation of ASIC channels in rat cerebellar Purkinje neurons by ischaemia
      related signals.
AB  - Acid-sensing ion channels (ASICs), activated by a decrease of extracellular pH,
      are found in neurons throughout the nervous system. They have an amino acid
      sequence similar to that of ion channels activated by membrane stretch, and have
      been implicated in touch sensation. Here we characterize the pH-dependent
      activation of ASICs in cerebellar Purkinje cells and investigate how they are
      modulated by factors released in ischaemia. Lowering the external pH from 7.4
      activated an inward current at -66 mV, carried largely by Na+ ions, which was
      half-maximal for a step to pH 6.4 and was blocked by amiloride and gadolinium.
      The H+-gated current desensitized within a few seconds, but approximately 30 % of
      cells showed a sustained inward current (11 % of the peak current) in response to
      the maintained presence of pH 6 solution. The peak H+-evoked current was
      potentiated by membrane stretch (which occurs in ischaemia when [K+]o rises) and
      by arachidonic acid (which is released when [Ca2+]i rises in ischaemia).
      Arachidonic acid increased to 77 % the fraction of cells showing a sustained
      current evoked by acid pH. The ASIC currents were also potentiated by lactate
      (which is released when metabolism becomes anaerobic in ischaemia) and by
      FMRFamide (which may mimic the action of related mammalian RFamide transmitters).
      These data reinforce suggestions of a mechanosensory aspect to ASIC channel
      function, and show that the activation of ASICs reflects the integration of
      multiple signals which are present during ischaemia.

PMID- 12205185
TI  - A-type potassium currents active at subthreshold potentials in mouse cerebellar
      Purkinje cells.
AB  - Voltage-dependent and calcium-independent K+ currents were whole-cell recorded
      from cerebellar Purkinje cells in slices. Tetraethylammonium (TEA, 4 mM)
      application isolated an A-type K+ current (I(K(A))) with a peak amplitude, at +20
      mV, of about one third of the total voltage-dependent and calcium-independent K+
      current. The I(K(A)) activated at about -60 mV, had a V(0.5) of activation of 
      24.9 mV and a V(0.5) of inactivation of -69.2 mV. The deactivation time constant
      at -70 mV was 3.4 +/- 0.4 ms, while the activation time constant at +20 mV was
      0.9 +/- 0.2 ms. The inactivation kinetics was weakly voltage dependent, with two
      time constants; those at +20 mV were 19.3 +/- 3.1 and 97.6 +/- 9.8 ms. The
      recovery from inactivation had two time constants of 60.8 ms (78.4 %) and 962.3
      ms (21.6 %). The I(K(A)) was blocked by 4-aminopyridine with an IC50 of 67.6
      microM. Agitoxin-2 (2 nM) blocked 17.4 +/- 2.1 % of the I(K(A)). Flecainide
      completely blocked the I(K(A)) with a biphasic effect with IC50 values of 4.4 and
      183.2 microM. In current-clamp recordings the duration of evoked action
      potentials was affected neither by agitoxin-2 (2 nM) nor by flecainide (3
      microM), but action potentials that were already broadened by TEA were further
      prolonged by 4-aminopyridine (100 microM). The amplitude of the hyperpolarisation
      at the end of depolarising steps was reduced by all these blockers.

PMID- 12205187
TI  - Capsaicin activation of glutamatergic synaptic transmission in the rat locus
      coeruleus in vitro.
AB  - The vanilloid receptor protein (VR1) is a well-characterised integrator of
      noxious stimuli in peripheral sensory neurones. There is evidence for the
      presence of VR1 in the central nervous system, but little information as to its
      role there. In this study we have examined the actions of agonists for VR1
      receptors in the rat locus coeruleus (LC), using whole-cell patch-clamp
      recordings from acutely isolated neurones and neurones in slices. Superfusion
      with capsaicin resulted in a concentration-dependent increase in the frequency of
      isolated miniature excitatory postsynaptic currents (mEPSCs) in LC neurones. The
      mean amplitude of the mEPSCs was not affected by capsaicin. The effects of
      capsaicin (1 microM) were abolished by the VR1 receptor antagonists capsazepine
      (10 microM) and iodoresiniferatoxin (300 nM). Removal of extracellular Ca2+
      abolished the capsaicin-induced increase in frequency of mEPSCs. Capsaicin
      superfusion had no consistent effects on evoked excitatory postsynaptic currents.
      Capsaicin superfusion also resulted in the release of an adrenoceptor agonist in
      the LC but did not affect the membrane currents of acutely isolated LC neurones.
      These data demonstrate that the VR1 receptor appears to be located
      presynaptically on afferents to the LC, and that activation of VR1 may serve to
      potentiate the release of glutamate and adrenaline/noradrenaline in this brain
      region.

PMID- 12205188
TI  - Brainstem modulation of visual response properties of single cells in the dorsal
      lateral geniculate nucleus of cat.
AB  - The dorsal lateral geniculate nucleus (dLGN) transmits visual signals from the
      retina to the cortex. In the dLGN the antagonism between the centre and the
      surround of the receptive fields is increased through intrageniculate inhibitory
      mechanisms. Furthermore, the transmission of signals through the dLGN is
      modulated in a state-dependent manner by input from various brainstem nuclei
      including an area in the parabrachial region (PBR) containing cholinergic cells
      involved in the regulation of arousal and sleep. Here, we studied the effects of
      increased PBR input on the spatial receptive field properties of cells in the
      dLGN. We made simultaneous single-unit recordings of the input to the cells from
      the retina (S-potentials) and the output of the cells to the cortex (action
      potentials) to determine spatial receptive field modifications generated in the
      dLGN. State-dependent modulation of the spatial receptive field properties was
      studied by electrical stimulation of the PBR. The results showed that PBR
      stimulation had only a minor effect on the modifications of the spatial receptive
      field properties generated in the dLGN. The PBR-evoked effects could be described
      mainly as increased response gain. This suggested that the spatial modifications
      of the receptive field occurred at an earlier stage of processing in the dLGN
      than the PBR-controlled gain regulation, such that the PBR input modulates the
      gain of the spatially modified signals. We propose that the spatial receptive
      field modifications occur at the input to relay cells through the synaptic
      triades between retinal afferents, inhibitory interneurone dendrites, and relay
      cell dendrites and that the gain regulation is related to postsynaptic
      cholinergic effects on the relay cells.

PMID- 12205189
TI  - Isotonic force modulates force redevelopment rate of intact frog muscle fibres:
      evidence for cross-bridge induced thin filament activation.
AB  - We tested the hypothesis that force-velocity history modulates thin filament
      activation, as assessed by the rate of force redevelopment after shortening
      (+dF/dt(R)). The influence of isotonic force on +dF/dt(R) was assessed by
      imposing uniform amplitude (2.55 to 2.15 microm sarcomere(-1)) but different
      speed releases to intact frog muscle fibres during fused tetani. Each release
      consisted of a contiguous ramp- and step-change in length. Ramp speed was changed
      from release to release to vary fibre shortening speed from 1.00 (2.76 +/- 0.11
      microm half-sarcomere(-1) s(-1)) to 0.30 of maximum unloaded shortening velocity
      (V(u)), thereby modulating isotonic force from 0 to 0.34 F(o), respectively. The
      step zeroed force and allowed the fibre to shorten unloaded for a brief period of
      time prior to force redevelopment. Although peak force redevelopment after
      different releases was similar, +dF/dt(R) increased by 81 +/- 6 % (P < 0.05) as
      fibre shortening speed was reduced from 1.00 V(u). The +dF/dt(R) after different
      releases was strongly correlated with the preceding isotonic force (r = 0.99, P <
      0.001). Results from additional experiments showed that the slope of slack test
      plots produced by systematically increasing the step size that followed each ramp
      were similar. Thus, isotonic force did not influence V(u) (mean: 2.84 +/- 0.10
      microm half-sarcomere(-1) s(-1), P < 0.05). We conclude that isotonic force
      modulates +dF/dt(R) independent of change in V(u), an outcome consistent with a
      cooperative influence of attached cross-bridges on thin filament activation that
      increases cross-bridge attachment rate without alteration to cross-bridge
      detachment rate.

PMID- 12205190
TI  - Passive transfer of Lambert-Eaton syndrome to mice induces dihydropyridine
      sensitivity of neuromuscular transmission.
AB  - Lambert-Eaton myasthenic syndrome (LEMS) is a paraneoplastic disorder in which
      autoantibodies apparently target the voltage-gated Ca2+ channels that regulate
      acetylcholine (ACh) release at motor nerve terminals. P/Q-type Ca2+ channels are
      primarily involved in ACh release at mammalian neuromuscular junctions. Passive
      transfer of LEMS to mice by repeated administration of plasma from LEMS patients
      reduces the amplitude of the perineurial P/Q-type current, and unmasks a
      dihydropyridine (DHP)-sensitive L-type Ca2+ current at the motor nerve terminal.
      The present study sought to determine if this DHP-sensitive component contributes
      to ACh release. Mice were treated for 30 days with plasma from healthy human
      controls or patients with LEMS. For some studies, diaphragms from naive mice were
      incubated with LEMS or control human plasma for 2 or 24 h. End-plate potentials
      (EPPs) and miniature end-plate potentials (MEPPs) were recorded from
      neuromuscular junctions in the hemidiaphragm. Treatment of mice with LEMS plasma
      evoked the characteristic electrophysiological signs of LEMS: reduced quantal
      content and facilitation of EPP amplitudes at high-frequency stimulation. Quantal
      content was also reduced in muscles incubated acutely with LEMS plasma.
      Nimodipine, a DHP-type blocker of L-type Ca2+ channels, did not significantly
      affect the quantal content of muscles treated for 2 or 24 h with either control
      or LEMS plasma, or following chronic treatment with control plasma. However,
      following 30 days treatment with LEMS plasma, nimodipine significantly reduced
      the remaining quantal content to 57.7 +/- 3.3 % of pre-nimodipine control levels.
      Thus, DHP-sensitive Ca2+ channels become involved in synaptic transmission at the
      mouse neuromuscular junction after chronic, but not acute treatment with LEMS
      plasma. However, reductions in quantal release of ACh occur even after very short
      periods of exposure to LEMS plasma. As such, development of the L-type Ca2+
      channel contribution to ACh release during passive transfer of LEMS appears to
      occur only after quantal release is significantly impaired for an extended
      duration, suggesting that an adaptive response of the ACh release apparatus
      occurs in LEMS.

PMID- 12205191
TI  - Disruption of the two-state membrane potential of striatal neurones during
      cortical desynchronisation in anaesthetised rats.
AB  - In anaesthetised animals, the very negative resting membrane potential of
      striatal spiny neurones (down state) is interrupted periodically by depolarising
      plateaux (up states) which are probably driven by excitatory input. In the
      absence of active synaptic input, as occurs in vitro, potassium currents hold the
      membrane potential of striatal spiny neurones in the down state. Because striatal
      spiny neurones fire action potentials only during the up state, these plateau
      depolarisations have been perceived as enabling events that allow information
      processing through cerebral cortex-basal ganglia circuits. Recent studies have
      demonstrated that the robust membrane potential fluctuation of spiny neurones is
      strongly correlated to the slow electroencephalographic rhythms that are typical
      of slow wave sleep and anaesthesia. To further understand the impact of cortical
      activity states on striatal function, we studied the membrane potential of
      striatal neurones during cortical desynchronised states. Simultaneous in vivo
      recordings of striatal neurones and the electrocorticogram in urethane
      anaesthetised rats revealed that rhythmic alternation between up and down states
      was disrupted during episodes of spontaneous or induced cortical
      desynchronisation. Instead of showing robust two-state fluctuations, the membrane
      potential of striatal neurones displayed a persisting depolarised state with
      fast, low-amplitude modulations. Spiny neurones remained in this persistent up
      state until the cortex resumed ~1 Hz synchronous activity. Most of the recorded
      neurones exhibited a low firing probability, irrespective of the cortical
      activity state. Time series analysis failed to reveal significant correlations
      between the membrane potential of striatal neurones and the desynchronised
      electrocorticogram. Our results suggest that during cortical desynchronisation
      continuous uncorrelated excitatory input sustains the membrane potential of
      striatal neurones in a persisting depolarised state, but that substantial
      additional input is necessary to impel the neurones to threshold. Our data
      support that the prevailing cortical activity state determines the duration of
      the enabling depolarising events that take place in striatal spiny neurones.

PMID- 12205192
TI  - Mechanisms of acid-induced activation of airway afferent nerve fibres in guinea
      pig.
AB  - The mechanisms underlying the response of airway afferent nerves to low pH were
      investigated in an isolated guinea-pig airway nerve preparation. Extracellular
      recordings were made from single jugular or nodose vagal ganglion neurons that
      projected their sensory fibers into the airways. The airway tissue containing the
      mechanically sensitive receptive fields was exposed into acidic solutions. Rapid
      and transient (approximately 3 s) administration of 1 mM citric acid to the
      receptive field consistently induced action potential discharge in nociceptive C
      fibers (41/44) and nodose Adelta fibres (29/30) that are rapidly adapting low
      threshold mechanosensors (RAR-like fibres). In contrast, citric acid activated
      only 8/17 high threshold mechanosensitive jugular Adelta fibres. The RAR-like
      fibres were slightly more sensitive than C-fibres to acidic solutions (pH
      threshold > 6.7). The RAR-like fibres response to the approximately 3 s acid
      treatment was not affected by a vanilloid receptor 1 (VR1) antagonist,
      capsazepine (10 microM), and was rapidly inactivating (action potential discharge
      terminated before the acid administration was completed). Gradual reduction of pH
      did not activate the RAR-like fibres even when the pH was reduced to
      approximately 5.0. The C-fibres responded to the gradual reduction of pH with
      persistent action potential discharge that was nearly abolished by capsazepine
      (10 microM) and inhibited by over 70 % with another VR1 antagonist iodo
      resiniferatoxin (1 microM). In contrast the C-fibre response to the transient
      approximately 3 s exposure to pH approximately 5.0 was not affected by the VR1
      antagonists. We conclude that activation of guinea-pig airway afferents by low pH
      is mediated by both slowly and rapidly inactivating mechanisms. We hypothesize
      that the slowly inactivating mechanism, present in C-fibres but not in RAR-like
      fibres, is mediated by VR1. The rapidly inactivating mechanism acts independently
      of VR1, has characteristics similar to acid sensing ion channels (ASICs) and is
      found in the airway terminals of both C-fibres and RAR-like fibres.

PMID- 12205193
TI  - Adrenergic signalling between rat taste receptor cells.
AB  - In taste buds, synaptic transmission is traditionally thought to occur from taste
      receptor cells to the afferent nerve. This communication reports the novel
      observation that taste receptor cells respond to adrenergic stimulation.
      Noradrenaline application inhibited outward potassium currents in a dose
      dependent manner. This inhibition was mimicked by the beta agonist isoproterenol
      and blocked by the beta antagonist propranolol. The alpha agonists clonidine and
      phenylephrine both inhibited the potassium currents and elevated intracellular
      calcium levels. Inwardly rectifying potassium currents were unaffected by
      adrenergic stimulation. Experiments using the RT-PCR technique demonstrate that
      lingual epithelium expresses multiple alpha (alpha1a, alpha1b, alpha1c, alpha1d,
      alpha2a, alpha2b, alpha2c) and beta (beta1, beta2) subtypes of adrenergic
      receptors, and immunocytochemistry localized noradrenaline to a subset of taste
      receptor cells. Collectively, these data imply strongly that adrenergic
      transmission within the taste bud may play a paracrine role in taste physiology.

PMID- 12205195
TI  - Transparency of the bovine corneal stroma at physiological hydration and its
      dependence on concentration of the ambient anion.
AB  - De-epithelialised and de-endothelialised bovine corneal stromas with a hydration
      of 3.2 equilibrated at 154 mM NaCl and buffered at pH 7.4 had their optical
      density (400-750 nm) measured. Stromas equilibrated against 10, 20, 30, 50 or 100
      mM NaCl made isotonic to 154 mM NaCl by supplementing with sorbitol were
      progressively more transparent as NaCl increased. Hypertonic equilibration
      against 300, 600 or 1000 mM NaCl resulted in a progressive loss of transparency
      compared with 154 mM NaCl. Light scattering as a function of wavelength fitted a
      lambda(-3) function well for 10, 30, 50, 100 and 154 mM NaCl preparations between
      450 and 650 nm, but not at higher wavelengths. However, hypertonic 300, 600 and
      1000 mM NaCl preparations showed a lambda(-2) dependence in the 450-750 nm range.
      Experiments with 154 mM NaCl and either 0 or 300 mM sorbitol suggested that the
      changes in light scattering in hypertonic preparations are unlikely to be caused
      by osmotic alterations to the stromal keratocytes. Psychophysical studies of the
      optical transmission function of preparations indicated that corneal stromas
      dialysed against 154 mM NaCl had usable optical properties, but preparations
      dialysed against 10 mM NaCl were effectively unable to transmit an image. The
      results are related to the known increase of fixed negative charge in the corneal
      matrix when chloride ions are adsorbed onto the matrix. It is suggested that the
      ordering force between corneal collagen fibrils, generated in part by anion
      binding, may be crucial to the physiological functioning of the visual system.

PMID- 12205194
TI  - Cytosolic Ca2+ triggers early afterdepolarizations and Torsade de Pointes in
      rabbit hearts with type 2 long QT syndrome.
AB  - The role of intracellular Ca2+ (Ca2+i) in triggering early afterdepolarizations
      (EADs), the origins of EADs and the mechanisms underlying Torsade de Pointes
      (TdP) were investigated in a model of long QT syndrome (Type 2). Perfused rabbit
      hearts were stained with RH327 and Rhod-2/AM to simultaneously map membrane
      potential (V(m)) and Ca2+i with two photodiode arrays. The I(Kr) blocker E4031
      (0.5 microM) together with 50 % reduction of [K+]o and [Mg2+]o elicited long
      action potentials (APs), V(m) oscillations on AP plateaux (EADs) then ventricular
      tachycardia (VT). Cryoablation of both ventricular chambers eliminated Purkinje
      fibres as sources of EADs. E4031 prolonged APs (0.28 to 2.3 s), reversed
      repolarization sequences (baseapex) and enhanced repolarization gradients (30 to
      230 ms, n = 12) indicating a heterogeneous distribution of I(Kr). At low [K+]o
      and [Mg2+]o, E4031 elicited spontaneous Ca2+iand V(m) spikes or EADs (3.5 +/- 1.9
      Hz) during the AP plateau (n = 6). EADs fired 'out-of-phase' from several sites,
      propagated, collided then evolved to TdP. Phase maps (Ca2+ivs. V(m)) had
      counterclockwise trajectories shaped like a 'boomerang' during an AP and like
      ellipses during EADs, with V(m) preceding Ca2+iby 9.2 +/- 1.4 (n = 6) and 7.2 +/-
      0.6 ms (n = 5/6), respectively. After cryoablation, EADs from surviving
      epicardium (~1 mm) fired at the same frequency (3.4 +/- 0.35 Hz, n = 6) as
      controls. At the origins of EADs, Ca2+ipreceded V(m) and phase maps traced
      clockwise ellipses. Away from EAD origins, V(m) coincided with or preceded Ca2+i.
      In conclusion, overload elicits EADs originating from either ventricular or
      Purkinje fibres and 'out-of-phase' EAD activity from multiple sites generates
      TdP, evident in pseudo-ECGs.

PMID- 12205196
TI  - Glycinergic inhibition is essential for co-ordinating cranial and spinal
      respiratory motor outputs in the neonatal rat.
AB  - Eupnoeic breathing in mammals is dependent on the co-ordinated activity of
      cranial and spinal motor outputs to both ventilate the lungs and adjust
      respiratory airflow, which they do by regulating upper-airway resistance. We
      investigated the role of central glycinergic inhibition in the co-ordination of
      cranial and spinal respiratory motor outflows. We developed an arterially
      perfused neonatal rat preparation (postnatal age 0-4 days) to assess the effects
      of blocking glycine receptors with systemically administered strychnine (0.5-1
      microM). We recorded respiratory neurones located within the ventrolateral
      medulla, inspiratory phrenic nerve activity (PNA) and recurrent laryngeal nerve
      activity (RLNA), as well as dynamic changes in laryngeal resistance. Central
      recordings of postinspiratory neurones revealed an earlier onset in firing
      relative to the onset of inspiratory PNA after exposure to strychnine (260 +/-
      38.9 vs. 129 +/- 26.8 ms). After glycine receptor blockade, postinspiratory
      neurones discharged during the inspiratory phase. Strychnine also evoked a
      decrease in PNA frequency (from 38.6 +/- 4.7 to 30.7 +/- 2.8 bursts min(-1)), but
      amplitude was unaffected. In control conditions, RLNA comprised inspiratory and
      postinspiratory discharges; the amplitude of the latter exceeded that of the
      former. However, after administration of strychnine, the amplitude of inspiratory
      related discharge increased (+65.2 +/- 15.2 %) and exceeded postinspiratory
      activity. Functionally this change in RLNA caused a paradoxical, inspiratory
      related glottal constriction during PNA. We conclude that during the first days
      of life in the rat, glycine receptors are essential for the formation of the
      eupnoeic-like breathing pattern as defined by the co-ordinated activity of
      cranial and spinal motor inspiratory and postinspiratory activities.

PMID- 12205197
TI  - Tetrodotoxin prevents motor unit enlargement after partial denervation in rat
      hindlimb muscles.
AB  - Findings that increased neuromuscular activity significantly reduced sprouting in
      partially denervated muscles prompted this present study to determine if the
      converse is true, namely that reduced activity promotes sprouting and motor unit
      (MU) enlargement. Partial denervation of rat hindlimb muscles by either the L4 or
      L5 spinal root avulsion resulted in extensive denervation (> 80 %) in tibialis
      anterior (TA) and medial gastrocnemius (MG) muscles, and moderate denervation
      (~50 %) in soleus (SOL) and plantaris (PL) muscles. The partially denervated
      muscles were then subjected to a 4 week programme of normal caged activity or TTX
      induced neuromuscular inactivity. At 1 month, measurement of MU enlargement and
      quantification of sprouting were evaluated, respectively, by electrophysiological
      and histochemical means. Analysis of electrophysiological data showed that MU
      forces were significantly increased in both extensively and moderately denervated
      muscles 1 month after partial denervation and normal cage activity and that
      neuromuscular activity blockade by TTX completely abolished the MU enlargement in
      these partially denervated muscles. Histochemical analysis of sprouting revealed
      that the number of sprouts was significantly increased after partial denervation
      and normal cage activity, particularly after extensive denervation. TTX-induced
      neuromuscular inactivity dramatically reduced the number of sprouts and increased
      the number of free endplates in the extensively but not the moderately denervated
      muscles. These data demonstrate that a reduction in neuromuscular activity
      mediated by presynaptic blockade of neural action potentials reduces MU
      enlargement in partially denervated muscles by reducing axonal sprouting.

PMID- 12205199
TI  - Effects of leptin on cat intestinal vagal mechanoreceptors.
AB  - Vagal afferent nerve fibres are involved in the transmission to the central
      nervous system of information relating to food intake and immune reactions.
      Leptin is involved in the control of food intake and has specific receptors in
      afferent vagal neurones. To investigate the role of these receptors, we studied
      the effects of leptin on single vagal afferent activities from intestinal
      mechanoreceptors in anaesthetized cats. The activity of 35 intestinal vagal
      mechanoreceptors was recorded by means of glass microelectrodes implanted in the
      nodose ganglion. Leptin (10 microg), administered into the artery irrigating the
      upper part of the intestine, induced activation in 17 units (P < 0.001),
      inhibition in 8 units (P < 0.05), and had no effect on 10 units. The excitatory
      effects of leptin were blocked by the endogenous interleukine-1beta receptor
      antagonist, (Il-1ra, 250 microg, I.A.). Cholecystokinin (CCK, 10 microg, I.A.)
      induced an activatory response only in the two types of units which were
      responsive to leptin alone. When leptin was administered after CCK, its
      excitatory effects were enhanced and its inhibitory effects were blocked, whereas
      it had no effect on the units which were not affected by leptin alone. The
      interactions between leptin and CCK are specific ones, since other substances
      (phenylbiguanide, a serotoninergic agonist; substance P) known to activate the
      mechanoreceptors did not modify the effects of leptin. These results indicate
      that leptin appears to play a role in the control of immune responses and food
      intake via intestinal vagal afferent nerve fibres and that there is a functional
      link between leptin and Il-1beta.

PMID- 12205198
TI  - Sleep-waking discharge patterns of median preoptic nucleus neurons in rats.
AB  - Several lines of evidence show that the preoptic area (POA) of the hypothalamus
      is critically implicated in the regulation of sleep. Functionally heterogeneous
      cell groups with sleep-related discharge patterns are located both in the medial
      and lateral POA. Recently a cluster of neurons showing sleep-related c-Fos
      immunoreactivity was found in the median preoptic nucleus (MnPN). To determine
      the specificity of the state-related behaviour of MnPN neurons we have undertaken
      the first study of their discharge patterns across the sleep-waking cycle. Nearly
      76 % of recorded cells exhibited elevated discharge rates during sleep. Sleep
      related units showed several distinct types of activity changes across sleep
      stages. Two populations included cells displaying selective activation during
      either non-rapid eye movement (NREM) sleep (10 %) or REM sleep (8 %). Neurons
      belonging to the predominant population (58 %) exhibited activation during both
      phases of sleep compared to wakefulness. Most of these cells showed a gradual
      increase in their firing rates prior to sleep onset, elevated discharge during
      NREM sleep and a further increase during REM sleep. This specific sleep-waking
      discharge profile is opposite to that demonstrated by wake-promoting
      monoaminergic cell groups and was previously found in cells localized in the
      ventrolateral preoptic area (vlPOA). We hypothesize that these vlPOA and MnPN
      neuronal populations act as parts of a GABAergic/galaninergic sleep-promoting
      ('anti-waking') network which exercises inhibitory control over waking-promoting
      systems. MnPN neurons that progressively increase activity during sustained
      waking and decrease activity during sustained sleep states may be involved in
      homeostatic regulation of sleep.

PMID- 12205200
TI  - Combined inhibition of nitric oxide and prostaglandins reduces human skeletal
      muscle blood flow during exercise.
AB  - The vascular endothelium is an important mediator of tissue vasodilatation, yet
      the role of the specific substances, nitric oxide (NO) and prostaglandins (PG),
      in mediating the large increases in muscle perfusion during exercise in humans is
      unclear. Quadriceps microvascular blood flow was quantified by near infrared
      spectroscopy and indocyanine green in six healthy humans during dynamic knee
      extension exercise with and without combined pharmacological inhibition of NO
      synthase (NOS) and PG by L-NAME and indomethacin, respectively. Microdialysis was
      applied to determine interstitial release of PG. Compared to control, combined
      blockade resulted in a 5- to 10-fold lower muscle interstitial PG level. During
      control incremental knee extension exercise, mean blood flow in the quadriceps
      muscles rose from 10 +/- 0.8 ml (100 ml tissue)(-1) min(-1) at rest to 124 +/-
      19, 245 +/- 24, 329 +/- 24 and 312 +/- 25 ml (100 ml tissue)(-1) min(-1) at 15,
      30, 45 and 60 W, respectively. During inhibition of NOS and PG, blood flow was
      reduced to 8 +/- 0.5 ml (100 ml tissue)(-1) min(-1) at rest, and 100 +/- 13, 163
      +/- 21, 217 +/- 23 and 256 +/- 28 ml (100 ml tissue)(-1) min(-1) at 15, 30, 45
      and 60 W, respectively (P < 0.05 vs. control). In conclusion, combined inhibition
      of NOS and PG reduced muscle blood flow during dynamic exercise in humans. These
      findings demonstrate an important synergistic role of NO and PG for skeletal
      muscle vasodilatation and hyperaemia during muscular contraction.

PMID- 12205201
TI  - Mechanisms of enhancement of human motor cortex excitability induced by
      interventional paired associative stimulation.
AB  - Associative stimulation has been shown to enhance excitability in the human motor
      cortex (Stefan et al. 2000); however, little is known about the underlying
      mechanisms. An interventional paired associative stimulation (IPAS) was employed
      consisting of repetitive application of single afferent electric stimuli,
      delivered to the right median nerve, paired with single pulse transcranial
      magnetic stimulation (TMS) over the optimal site for activation of the abductor
      pollicis brevis muscle (APB) to generate approximately synchronous events in the
      primary motor cortex. Compared to baseline, motor evoked potentials (MEPs)
      induced by unconditioned, single TMS pulses increased after IPAS. By contrast,
      intracortical inhibition, assessed using (i) a suprathreshold test TMS pulse
      conditioned by a subthreshold TMS pulse delivered 3 ms before the test pulse, and
      (ii) a suprathreshold test TMS pulse conditioned by afferent median nerve
      stimulation delivered 25 ms before the TMS pulse, remained unchanged when
      assessed with appropriately matching test stimulus intensities. The increase of
      single-pulse TMS-evoked MEP amplitudes was blocked when IPAS was performed under
      the influence of dextromethorphan, an N-methyl-D-aspartate (NMDA) receptor
      antagonist known to block long-term potentiation (LTP). Further experiments
      employing the double-shock TMS protocol suggested that the afferent pulse, as one
      component of the IPAS protocol, induced disinhibition of the primary motor cortex
      at the time when the TMS pulse, as the other component of IPAS, was delivered.
      Together, these findings support the view that LTP-like mechanisms may underlie
      the cortical plasticity induced by IPAS.

PMID- 12205202
TI  - Obstacle avoidance during human walking: transfer of motor skill from one leg to
      the other.
AB  - The aim of this study was to evaluate whether a newly acquired locomotor skill
      can be transferred to the mirror condition. Subjects were trained to step over an
      obstacle on a treadmill, the appearance of which was signalled by an acoustic
      stimulus, while visual information was prevented. Feedback information about foot
      clearance was provided by acoustic signals. During two successive runs (each
      consisting of 100 steps over the obstacle) the same leg was leading (i.e. the leg
      crossing the obstacle first). In the following third run, the leading and
      trailing legs were changed. During each of the three successive runs the
      adaptational changes were analysed by recording leg muscle electromyographic
      (EMG) activity, joint angle trajectories and foot clearance over the obstacle.
      The training effect gained between the first and second runs and the transfer to
      the mirror condition (third run) were evaluated. Adaptational changes of all
      measures, except ankle joint trajectory, could to a significant extent be
      transferred to the mirror condition. No side-specific differences in the amount
      of transfer were found, neither from the right to the left side, nor vice versa.
      These observations are at variance with adaptational changes observed during
      split-belt walking or one-legged hopping on a treadmill, where no transfer to the
      mirror condition occurred. It is assumed that this might be due to the specific
      requirements of the tasks and the leg muscles involved. While in the split-belt
      and hopping experiments leg extensor muscles are mainly involved, leg flexors
      predominate in the performance of the present task. It is hypothesised that the
      learning effects observed in the present experiments are mediated at a higher
      level (e.g. brainstem) of locomotor control.

PMID- 12205203
TI  - Model simulations of cardiovascular changes at the onset of moderate exercise in
      humans.
AB  - We have tested whether the cardiovascular changes at the onset of exercise could
      be simulated only by an increase in the baroreflex set point and locally induced
      vasodilatation in the exercising muscles. The mathematical model consists of a
      heart, a linear elastic arterial reservoir and two parallel resistive vascular
      beds. The arterial baroreflex loop is modelled by three separate time domain
      processing objects, each with its own gain, time constant and delay. These are
      intended to simulate the action of a sympathetic signal to the peripheral
      vascular bed, a parasympathetic signal to the heart and a sympathetic signal to
      the heart. We used this model with previously published experimental data to
      estimate the unknown parameters in the reflex control loop. In all 10 subjects
      and in the global averaged response, the short-term cardiovascular responses were
      adequately simulated by using individual sets of parameters in the model. An
      increase in the baroreflex set point and locally induced vasodilatation in the
      exercising muscles can explain almost all of the cardiovascular changes in the
      recorded variables (mean arterial pressure, RR interval and stroke volume) at the
      onset of exercise.

PMID- 12205204
TI  - Feral children.

PMID- 12205205
TI  - Expert witnesses, courts and the law.

PMID- 12205206
TI  - A simple index for detection of gestational diabetes mellitus.
AB  - The conventional screening test for gestational diabetes mellitus is measurement
      of plasma glucose 1 hour after 50 g glucose by mouth. The sensitivity and
      specificity of this test are lower than desirable; we therefore developed an
      index including other plasma constituents. In a preliminary study, 138 pregnant
      women had the standard oral glucose load screening test, and plasma fructosamine
      and total proteins were measured, in addition to glucose, in the 1-hour samples.
      An index value (I) was calculated as [fructosamine (micro mol/L) divided by total
      proteins (g/L)]x[glucose (mmol/L) divided by 100]. Cut-off values for I were then
      assessed in a second prospective study, of 642 pregnant women. Definitive
      diagnosis of gestational diabetes was by oral glucose tolerance test (OGTT). The
      index was also assessed in terms of fetal macrosomia (birthweight>or=4000 g).
      With a cut-off value of I=27.2, sensitivity was 98%, specificity 89%, diagnostic
      efficiency 90%, positive likelihood ratio 8.76. Application of the index would
      have avoided 42% of the OGTTs demanded by the standard screening test, reducing
      false positives from about 24% to 10%. Predictive efficacy for macrosomia was
      10.3% versus 7.9%. Our index offers an efficient screening test for gestational
      diabetes, and with more stringent cut-off points may be applicable as a single
      step diagnostic procedure.

PMID- 12205207
TI  - A comparison of patients with chronic fatigue syndrome attending separate fatigue
      clinics based in immunology and psychiatry.
AB  - Hospital clinics for patients with chronic unexplained fatigue are held in
      departments of various disciplines. This causes difficulties for referrers in
      choosing the appropriate clinic and for researchers in generalizing findings from
      one type of clinic to others. We randomly selected 37 outpatients attending an
      immunology fatigue clinic and 36 outpatients attending a psychiatry fatigue
      clinic, all of whom had chronic fatigue syndrome. We compared demographic
      factors, symptoms, disability, quality of life, psychological distress and
      illness attributions. The patients from the two clinics were closely similar in
      their specific symptoms, disability, quality of life, psychological distress and
      previous attendance to mental health professionals. Psychological distress was
      high and equal in the two samples. The proportion of men was greater among
      patients attending the immunology clinic. In a post-hoc analysis, 64% of
      immunology attenders attributed their fatigue to physical factors, compared with
      31% of psychiatry clinic attenders (chi(2)=6.35, 1 d.f., P=0.01). These findings
      suggest that research data from one type of chronic fatigue clinic can be
      generalized to others. Clinically similar patients are referred to different
      clinics, and the choice of clinic may be influenced by the patients' illness
      beliefs. The high levels of emotional distress suggest that psychosocial
      management is as important as physical management in hospital outpatients with
      chronic fatigue syndrome, irrespective of its aetiology.

PMID- 12205208
TI  - Cardiovascular autonomic dysfunction in Africans infected with human
      immunodeficiency virus.
AB  - The effects of human immunodeficiency virus (HIV) on cardiovascular autonomic
      function have been little investigated in African patients. We performed standard
      heart-rate and blood pressure tests on 75 consecutive consenting patients
      referred for an HIV test in Yaounde, Cameroon. 54 patients proved to be HIV
      infected (30 having progressed to AIDS). Cardiovascular autonomic dysfunction was
      present in 8 (28%) patients with AIDS and in 1 (4%) HIV-positive patient without
      AIDS; no HIV-negative individuals had abnormal results. If borderline results are
      included, over 80% of HIV-positive patients had cardiovascular autonomic
      dysfunction. In HIV-infected patients, simple tests such as blood pressure
      responses to standing or handgrip can warn of cardiovascular autonomic
      dysfunction, thus signalling the need for added precautions when invasive
      procedures are proposed.

PMID- 12205209
TI  - Influence of a nurse practitioner on non-attendance rate for barium enema.
AB  - Non-attendance for barium enema investigation wastes resources, prolongs waiting
      times and delays diagnosis of colorectal carcinoma. In an inner-city hospital
      with a previous non-attendance rate of over 20% for barium enema we investigated
      the value of systematic personal contact with a nurse practitioner at the time of
      booking. We compared two groups of patients, all of whom received an explanation
      of the procedure from the referring clinician. Patients referred from the
      colorectal clinic were accompanied by the colorectal nurse practitioner to the
      radiology department for booking, an appointment being sent later by mail. The
      nurse practitioner reiterated the details of the procedure, provided
      supplementary information, confirmed the patient's contact details and provided a
      telephone number in case further information or assistance was needed. Patients
      referred from the gastroenterology clinic were managed as previously, making
      their own way to the radiology department and receiving supplementary information
      only on request. The patients referred from the two clinics were closely similar;
      however, the non-attendance rate for the intervention (colorectal) clinic was
      4/157 (2.5%) compared with 17/110 (15.5%) for the comparison clinic (P<0.001). A
      year previously the non-attendance rates in these clinics had been 23% and 20%,
      respectively. These results indicate that personal contact, with supplementary
      information, can substantially reduce the non-attendance rate for barium enema.

PMID- 12205210
TI  - Can hospital transfusion committees change transfusion practice?
AB  - Blood and blood products are commonly over-used in hospital practice. We
      investigated whether the introduction of a red-cell transfusion trigger
      (haemoglobin <8 g dL(-1)) influenced transfusion practice in surgery. Coronary
      artery bypass grafts (CABGs, n=400), total hip replacements (n=107), colectomies
      (n=85) and transurethral prostatectomies (TURPs, n=158) were reviewed over two
      periods of six months, before and after the introduction of the policy by the
      local hospital transfusion committee. After introduction of the policy, the
      proportion of patients transfused fell from 57% to 45% with CABGs (P=0.02) and
      from 52% to 26% with hip replacements (P=0.006); for colectomies and TURPs there
      was no change. Hospital stay did not increase in any of the groups. In the second
      period, haemoglobin concentration on discharge was lower after total hip
      replacement, by a mean (95% CI) of 0.7 (0.3-1.2) g dL(-1) (P=0.002) and after
      colectomy, by a mean of 0.6 (0.1-1.1) g dL(-1) (P=0.03). Although other factors
      cannot be excluded, we suggest that the reductions in red-cell transfusion were
      in large part attributable to the new transfusion policy.

PMID- 12205211
TI  - Starting insulin therapy in elderly patients.

PMID- 12205212
TI  - Management of pain in sickle-cell disease.

PMID- 12205213
TI  - Morphea presenting as widespread oedema.

PMID- 12205214
TI  - Incidental splenic artery aneurysm.

PMID- 12205215
TI  - Hyponatraemia without hypovolaemia.

PMID- 12205216
TI  - Stevens' cure: a secret remedy.

PMID- 12205217
TI  - Hospice: a global network.

PMID- 12205218
TI  - Mendel-forgotten or ignored?

PMID- 12205219
TI  - The safety of homeopathic products.

PMID- 12205220
TI  - Delayed diagnosis of slipped upper femoral epiphysis.

PMID- 12205221
TI  - Decline in autopsy rate.

PMID- 12205222
TI  - Sternoclavicular dislocations.

PMID- 12205223
TI  - Unkept outpatient appointments.

PMID- 12205224
TI  - Neuromuscular blocking drugs.

PMID- 12205225
TI  - Animal experiments and the doctor.

PMID- 12205228
TI  - Waiting in the NHS.

PMID- 12205229
TI  - Critical evaluation of smallpox vaccination for laboratory workers.

PMID- 12205231
TI  - Work organisation and unintentional sleep: results from the WOLF study.
AB  - BACKGROUND: Falling asleep at work is receiving increasing attention as a cause
      of work accidents. AIMS: To investigate which variables (related to work,
      lifestyle, or background) are related to the tendency to fall asleep
      unintentionally, either during work hours, or during leisure time. METHODS: 5589
      individuals (76% response rate) responded to a questionnaire. A multiple logistic
      regression analysis of the cross sectional data was used to estimate the risk of
      falling asleep. RESULTS: The prevalence for falling asleep unintentionally at
      least once a month was 7.0% during work hours and 23.1% during leisure time. The
      risk of unintentional sleep at work was related to disturbed sleep, having shift
      work, and higher socioeconomic group. Being older, being a woman, and being a
      smoker were associated with a reduced risk of unintentionally falling asleep at
      work. Work demands, decision latitude at work, physical load, sedentary work,
      solitary work, extra work, and overtime work were not related to falling asleep
      at work. Removing "disturbed sleep" as a predictor did not change the odds ratios
      of the other predictors in any significant way. With respect to falling asleep
      during leisure time, disturbed sleep, snoring, high work demands, being a smoker,
      not exercising, and higher age (>45 years) became risk indicators. CONCLUSION:
      The risk of involuntary sleep at work is increased in connection with disturbed
      sleep but also with night work, socioeconomic group, low age, being a male, and
      being a non-smoker.

PMID- 12205230
TI  - Occupational exposure assessment in case-control studies: opportunities for
      improvement.
AB  - Community based case-control studies are an efficient means to study disease
      aetiologies, and may be the only practical means to investigate rare diseases.
      However, exposure assessment remains problematic. We review the literature on the
      validity and reliability of common case-control exposure assessment methods:
      occupational histories, job-exposure matrices (JEMs), self reported exposures,
      and expert assessments. Given the variable quality of current exposure assessment
      techniques, we suggest methods to improve assessments, including the
      incorporation of hygiene measurements: using data from administrative exposure
      databases; using results of studies identifying determinants of exposure to
      develop questionnaires; and where reasonable given latency and biological half
      life considerations, directly measuring exposures of study subjects.

PMID- 12205232
TI  - Risk factors for occupational knee related disability among enlisted women in the
      US Army.
AB  - AIMS: To identify sociodemographic and occupational determinants of knee related
      disability discharge from the US Army among enlisted women, and to investigate
      effect modification. METHODS: A case-control study of 692 cases of knee related
      disability discharge and 2080 incidence density matched controls nested within
      the population of all 244 000 enlisted women on active duty in the US Army, 1980
      97. We used logistic regression to identify determinants of disability,
      stratified to explore effect modification by demographic and work
      characteristics. RESULTS: The risk of disability discharge was twice as high
      (odds ratio (OR) 2.4, 95% confidence interval (CI): 1.71 to 3.47) for the oldest
      (33-60 years) versus the youngest (17-21 years) women. Non-whites had lower risk
      than whites (OR 0.5, 95% CI: 0.41 to 0.60), as did married (OR 0.7, 95% CI: 0.54
      to 0.81) relative to non-married women. Those of lower rank (pay grades E1-E3)
      were at five times the risk of disability discharge compared to those of higher
      ranks (pay grades E4-E9, OR 5.0, 95% CI: 2.86 to 8.33), while ORs were highest
      for those with longer duration of service compared to women on active duty for a
      year or less (OR 1.4, 95% CI: 0.8 to 2.55 after 12 years). Race modified several
      effects, including that of rank. Age, duration of service, and pay grade were too
      highly correlated to draw firm conclusions about their independent modifying
      effects on risk of disability discharge from the Army. CONCLUSIONS:
      Sociodemographic factors had larger effects than occupational characteristics on
      risk of knee related disability discharge from the US Army. Interactions suggest
      subgroups at differing risk levels that might be targeted for more detailed
      investigations.

PMID- 12205233
TI  - Occupational exposure to cytotoxic drugs in two UK oncology wards.
AB  - AIMS: To investigate the potential exposure to cytotoxic drugs of staff on two
      oncology wards in a large district, UK hospital under normal working conditions.
      METHODS: Cytotoxic drug exposure was monitored in urine samples, surface wipes,
      and on disposable gloves by using a number of commonly used marker drugs, namely
      cyclophosphamide, ifosfamide, methotrexate, and the platino coordinated drugs.
      Questionnaire data on their work practices, potential exposure, use of protective
      personal equipment, and relevant training were collected from nursing, domestic,
      and clerical staff on two oncology wards. RESULTS: The majority of staff were
      female with a mean age of 31 years. Roughly half of the staff studied were
      specifically trained nurses with an average of 3.5 years experience of
      administering cytotoxic drugs. No cytotoxic drug preparation or reconstitution
      was carried out on the wards. Disposable gloves, plastic armlets and aprons, but
      not eye protection, were invariably worn where there was potential exposure to
      cytotoxics. No cytotoxic drug was detected in any of the staff's urine samples.
      Isolated disposable latex gloves from nurses administering drugs showed some
      contamination, as did some surfaces within the wards' sluice rooms, but not in
      the ward areas where the drugs were stored and checked prior to administration.
      CONCLUSIONS: The risk management strategies in place, including use of personal
      protective equipment, staff training, and other organisational measures, have
      ensured that internal exposure is lower than the detection limits for the current
      biological monitoring methods. Levels of contamination appear significantly lower
      than earlier, non-UK published studies where different risk management strategies
      were in place and, in particular, ward staff may have been involved in some
      degree of cytotoxic drug reconstitution.

PMID- 12205234
TI  - Cancer at sea: a case-control study among male Finnish seafarers.
AB  - AIMS: To study the possible work related reasons for the increased incidence of
      many cancers among seafarers. METHODS: A case-control study, nested in a cohort
      of all male seafarers (n = 30 940) who, according to the files of the Seamen's
      Pension Fund, had worked on board Finnish ships for any time during the period
      1960-80. Cases of cancer of the lung, nervous system, kidney, and pancreas,
      leukaemia, lymphoma, and all cases histologically defined as mesotheliomas were
      identified from the Finnish Cancer Registry in 1967-92. The preceding numbers of
      years at sea in various occupational categories were collected according to the
      type of ship (dry cargo ship, tanker, passenger vessel, icebreaker, other
      vessel). RESULTS: The incidence for lung cancer among engine crew increased with
      the increase in employment time, the odds ratio (OR) after three years being 1.68
      (95% CI 1.17 to 2.41). The OR of lung cancer for deck officers was 0.42 (95% CI
      0.29 to 0.61). Deck personnel on icebreakers had a significantly increased risk
      of lung cancer > or =20 years after first employment (OR 3.41, 95% CI 1.23 to
      9.49). The OR for mesothelioma among engine crew with a latency of 20 years was
      9.75 (95% CI 1.88 to 50.6). The OR for renal cancer among deck officers after
      three years employment was 2.15 (95% CI 1.14 to 4.08), but there was no increase
      by employment time or by latency. A rise of OR for lymphoma was detected among
      deck personnel on tankers, if the employment had lasted over three years (OR
      2.78, 95% CI 0.98 to 7.92). The risk pattern for leukaemia was similar to that of
      lymphoma, the OR among deck personnel on tankers varying from 2.26 (95% CI 1.01
      to 5.06) to 6.86 (95% CI 1.62 to 28.8) depending on the length of employment.
      CONCLUSIONS: Results indicate that occupational exposures of deck crews on
      tankers add to their risk of renal cancer, leukaemia, and possibly lymphoma.
      Engine crews have an asbestos related risk of mesothelioma, and the engine room
      conditions also seem to increase risk of lung cancer.

PMID- 12205236
TI  - Validity of empirical models of exposure in asphalt paving.
AB  - AIMS: To investigate the validity of empirical models of exposure to bitumen fume
      and benzo(a)pyrene, developed for a historical cohort study of asphalt paving in
      Western Europe. METHODS: Validity was evaluated using data from the USA, Italy,
      and Germany not used to develop the original models. Correlation between observed
      and predicted exposures was examined. Bias and precision were estimated. RESULTS:
      Models were imprecise. Furthermore, predicted bitumen fume exposures tended to be
      lower (-70%) than concentrations found during paving in the USA. This apparent
      bias might be attributed to differences between Western European and USA paving
      practices. Evaluation of the validity of the benzo(a)pyrene exposure model
      revealed a similar to expected effect of re-paving and a larger than expected
      effect of tar use. Overall, benzo(a)pyrene models underestimated exposures by
      51%. CONCLUSIONS: Possible bias as a result of underestimation of the impact of
      coal tar on benzo(a)pyrene exposure levels must be explored in sensitivity
      analysis of the exposure-response relation. Validation of the models, albeit
      limited, increased our confidence in their applicability to exposure assessment
      in the historical cohort study of cancer risk among asphalt workers.

PMID- 12205237
TI  - Urinary bisphenol A and plasma hormone concentrations in male workers exposed to
      bisphenol A diglycidyl ether and mixed organic solvents.
AB  - AIMS: To evaluate effects of exposure to bisphenol A diglycidyl ether (BADGE) on
      urinary excretion of bisphenol A, and plasma gonadotrophic hormones and
      testosterone in male epoxy resin sprayers. METHODS: Cross sectional study of 42
      workers whose job was to spray epoxy resin hardening agents including BADGE and
      mixed organic solvents, and 42 matched control workers without BADGE use in the
      same machine plants. RESULTS: Concentrations of urinary bisphenol A were higher
      in the epoxy resin sprayers (median 1.06 micro mol/mol creatinine) compared with
      the controls (median 0.52 micro mol/mol creatinine). Urinary metabolite
      concentrations of organic solvents used were all higher in the epoxy resin
      workers compared with the controls. Endocrinological examination showed different
      concentrations of follicle stimulating hormone (FSH) between the epoxy sprayers
      (median 5.3 mIU/ml) and the controls (median 7.6 mIU/ml). FSH showed a mild
      correlation with urinary bisphenol A, but not with the metabolites of organic
      solvents. Luteinising hormone and free testosterone concentrations did not differ
      between the two groups. CONCLUSION: BADGE may generate bisphenol A endogenously.
      Results suggest that bisphenol A may disrupt secretion of gonadotrophic hormones
      in men. The clinical significance of endocrine disrupting effects by bisphenol A
      should be further investigated in male workers exposed to bisphenol A.

PMID- 12205238
TI  - Lung function over six years among professional divers.
AB  - AIMS: To analyse longitudinal changes in pulmonary function in professional
      divers and their relation with cumulative diving exposure. METHODS: The study
      included 87 men at the start of their education as professional divers. At follow
      up one, three, and six years later, 83, 81, and 77 divers were reexamined. The
      median number of compressed air dives in the 77 divers over the follow up period
      was 196 (range 37-2000). A group of non-smoking policemen (n = 64) were subjected
      to follow up examinations in parallel with the divers. Assessment of lung
      function included dynamic lung volumes, maximal expiratory flow rates, and
      transfer factor for carbon monoxide (Tl(CO)). The individual rates of change of
      the lung function variables were calculated by fitting linear regression lines to
      the data, expressed as percent change per year. RESULTS: The annual reductions in
      forced vital capacity (FVC) and forced expired volume in one second (FEV(1)) were
      0.91 (SD 1.22) and 0.84 (SD 1.28) per cent per year in divers, which were
      significantly higher than the reductions in the policemen of 0.24 (SD 1.04) and
      0.16 (SD 1.07) per cent per year (p < 0.001). The annual reduction in the maximal
      expiratory flow rates at 25% and 75% of FVC expired (FEF(25%) and FEF(75%)) were
      related to the log(10) transformed cumulative number of dives in a multiple
      regression analysis (p < 0.05). The annual reductions in Tl(CO) were 1.33 (SD
      1.85) and 0.43 (SD 1.53) per cent per year in divers and policemen (p < 0.05).
      CONCLUSIONS: FVC, FEV(1), maximal expiratory flow rates, and Tl(CO) were
      significantly reduced in divers over the follow up period when compared with
      policemen. The contrasts within and between groups suggest that diving has
      contributed to the reduction in lung function.

PMID- 12205239
TI  - Occupational exposure to noise and the attributable burden of hearing
      difficulties in Great Britain.
AB  - AIMS: To determine the prevalence of self reported hearing difficulties and
      tinnitus in working aged people from the general population, and to estimate the
      risks from occupational exposure to noise and the number of attributable cases
      nationally. METHODS: A questionnaire was mailed to 22 194 adults of working age
      selected at random from the age-sex registers of 34 British general practices (21
      201 subjects) and from the central pay records of the British armed services (993
      subjects). Information was collected on years of employment in a noisy job; and
      whether the respondent wore a hearing aid, had difficulty in hearing
      conversation, or had experienced persistent tinnitus over the past year.
      Associations of hearing difficulty and tinnitus with noise exposure were examined
      by logistic regression, with adjustment for age, sex, smoking habits, and
      frequent complaints of headaches, tiredness, or stress. The findings were
      expressed as prevalence ratios (PRs) with associated 95% confidence intervals
      (CIs). Attributable numbers were calculated from the relevant PRs and an estimate
      of the prevalence of occupational exposure to noise nationally. RESULTS: Some 2%
      of subjects reported severe hearing difficulties (wearing a hearing aid or having
      great difficulty in both ears in hearing conversation in a quiet room). In men,
      the prevalence of this outcome rose steeply with age, from below 1% in those aged
      16-24 years to 8% in those aged 55-64. The pattern was similar in women, but
      severe hearing loss was only about half as prevalent in the oldest age band.
      Tinnitus was far more common in subjects with hearing difficulties. In both
      sexes, after adjustment for age, the risk of severe hearing difficulty and
      persistent tinnitus rose with years spent in a noisy job. In men older than 35
      years with 10 or more years of exposure, the PR for severe hearing difficulty was
      3.8 (95% CI 2.4 to 6.2) and that for persistent tinnitus 2.6 (95% CI 2.0 to 3.4)
      in comparison with those who had never had a noisy job. Nationally, some 153 000
      men and 26 000 women aged 35-64 years were estimated to have severe hearing
      difficulties attributable to noise at work. For persistent tinnitus the
      corresponding numbers were 266 000 and 84 000. CONCLUSIONS: Significant hearing
      difficulties and tinnitus are quite common in men from the older working age
      range. Both are strongly associated with years spent in a noisy occupation--a
      predominantly male exposure. The national burden of hearing difficulties
      attributable to noise at work is substantial.

PMID- 12205240
TI  - Raynaud's phenomenon, vibration induced white finger, and difficulties in
      hearing.
AB  - BACKGROUND: An association has previously been reported between finger blanching
      and hearing difficulties, but only in workers with exposure to noise and hand
      transmitted vibration (HTV). AIMS: To explore the association in a community
      sample, including cases who lacked occupational exposure to noise or HTV. METHOD:
      A questionnaire was mailed to 12 606 subjects aged 35-64 years, chosen at random
      from the age-sex registers of 34 British general practices. Inquiry was made
      about years of employment in noisy jobs, lifetime exposure to HTV, hearing
      difficulties and tinnitus, and lifetime history of cold induced finger blanching.
      Subjects were classed as having severe hearing difficulty if they used a hearing
      aid or found it difficult or impossible to hear conversation in a quiet room.
      Associations of finger blanching with hearing difficulties and tinnitus were
      analysed by logistic regression. RESULTS: Among 8193 respondents were 185 who
      reported severe hearing difficulty and 1151 who reported finger blanching. After
      adjustment for age and years of work in noisy jobs, hearing difficulty was about
      twice as common in men and women who reported finger blanching, including those
      who had never been importantly exposed to noise and in those never exposed to
      HTV. CONCLUSIONS: These data support an association between finger blanching and
      hearing loss, which is not explained by confounding occupational exposure to
      noise, and suggest that it may extend to causes of blanching other than vibration
      induced white finger. Further investigations are warranted to confirm the
      association and explore possible mechanisms, such as sympathetic vasoconstriction
      in the cochlea.

PMID- 12205241
TI  - Chrysotile and tremolite asbestos fibres in the lungs and parietal pleura of
      Corsican goats.
AB  - BACKGROUND AND AIMS: Environmental exposures to chrysotile and tremolite from the
      soil cause pleural plaques and mesothelioma in northeast Corsica. Goats grazing
      in the contaminated areas inhale asbestos fibres. We used this natural animal
      model to study whether these exposures actually result in increased fibre burdens
      in the lungs and parietal pleura. METHODS: Ten goats from areas with asbestos
      outcrops and two from other areas were slaughtered. Fibre content of lung and
      parietal pleural samples was determined by analytical transmission electron
      microscopy. RESULTS: Both chrysotile and tremolite fibres were detected. In the
      exposed goats, the geometric mean concentrations of asbestos fibres longer than 1
      microm were 0.27 x 10(6) fibres/g dry lung tissue and 1.8 x 10(6) fibres/g dry
      pleural tissue. Asbestos fibres were not detected in the lungs of the two control
      goats. Chrysotile fibres shorter than 5 microm were predominant in the parietal
      pleura. Tremolite fibres accounted for 78% and 86% of the fibres longer than 5
      microm in lung and parietal pleural samples, respectively. CONCLUSIONS:
      Environmental exposure in northeast Corsica results in detectable chrysotile and
      tremolite fibre loads in the lung and parietal pleura of adult goats. Tremolite
      fibres of dimensions with a high carcinogenic potency are detected in the
      parietal pleura.

PMID- 12205242
TI  - Competency in occupational health.

PMID- 12205243
TI  - Neurobehavioural testing in workers occupationally exposed to lead.

PMID- 12205244
TI  - Are incinerator workers exposed to PCDDs and PCDFs?

PMID- 12205245
TI  - Importance of work intensity on respiratory problems in hairdressers.

PMID- 12205246
TI  - Suicide mortality among electricians.

PMID- 12205247
TI  - Perinatal screening for group B streptococci: cost-benefit analysis of rapid
      polymerase chain reaction.
AB  - OBJECTIVE: To evaluate the costs and benefits of a group B streptococci screening
      strategy using a new, rapid polymerase chain reaction test in a hypothetical
      cohort of expectant mothers in the United States. METHODS:  DESIGN: Cost-benefit
      analysis using the human capital method. We developed a decision model to analyze
      the costs and benefits of a hypothetical group B streptococci screening strategy
      using a new, rapid polymerase chain reaction test as compared with the currently
      recommended group B streptococci screening guidelines-prenatal culture performed
      at 35 to 37 weeks or risk-factor-based strategy with subsequent intrapartum
      treatment of the expectant mothers with antibiotics to prevent early-onset group
      B streptococcal infections in their infants. PARTICIPANTS: A hypothetical cohort
      of pregnant women and their newborns. INTERVENTIONS: Screening strategies for
      group B streptococci using the new polymerase chain reaction technique, the 35-
      to 37-week culture, or maternal risk factors. OUTCOME MEASURES: Infant infections
      averted, infant deaths, infant disabilities, costs, and societal benefits of
      healthy infants. RESULTS: A screening strategy using the new polymerase chain
      reaction test generates a net benefit of $7 per birth when compared with the
      maternal risk-factor strategy. For every 1 million births, 80 700 more women
      would receive antibiotics, 884 fewer infants would become infected with early
      onset group B streptococci, and 23 infants would be saved from death or
      disability. The polymerase chain reaction-based strategy generates a net benefit
      of $6 per birth when compared with the 35- to 37-week prenatal culture strategy
      and results in fewer maternal courses of antibiotics (64 080 per million births),
      fewer perinatal infections with early-onset group B streptococci (218/million),
      and a reduction in 6 infant deaths and severe infant disability per million
      births. The benefits hold over a wide range of assumptions regarding key factors
      in the analysis. CONCLUSIONS: Although additional clinical trials are needed to
      establish the accuracy of this new polymerase chain reaction test, initial
      studies suggest that strategies using this test will be superior to the other 2
      strategies. Using the rapid polymerase chain reaction test becomes less
      attractive as the cost of the test increases. The test's greatest strengths lie
      in its ability to identify women and infants at risk at the time of labor,
      thereby decreasing the number of false-positives and false-negatives seen with
      the other 2 strategies and allowing for more accurate and effective intrapartum
      prophylaxis.

PMID- 12205248
TI  - Rate, risk factors, and outcomes of nosocomial primary bloodstream infection in
      pediatric intensive care unit patients.
AB  - OBJECTIVE: The objective of this study was to determine the rate, risk factors,
      and outcomes of nosocomial primary bloodstream infection in pediatric intensive
      care unit (PICU) patients. DESIGN: Prospective cohort study. SETTINGS: This study
      was performed at St Louis Children's Hospital, a 235-bed academic tertiary care
      center with a combined 22-bed medical and surgical PICU. PATIENTS: Subjects for
      this study were patients admitted to the PICU between September 1, 1999, and May
      31, 2000. INTERVENTIONS: None. OUTCOME MEASURES: Patients were monitored for the
      development of nosocomial bloodstream infections from the day of PICU admission
      until 48 hours after PICU discharge. RESULTS: Of 911 patients, 526 (58%) were
      male and 674 (74%) were white. Congenital heart disease (29%), lung disease
      (25%), and genetic syndrome (18%) were common. There were 65 episodes of primary
      bloodstream infection in 57 patients; 5 were polymicrobial and 7 patients had
      multiple bloodstream infections. Coagulase-negative Staphylococcus was the
      leading cause of bloodstream infection (n = 28), followed by Enterobacter cloacae
      (n = 8). The rate of bloodstream infection was 13.8 per 1000 central venous
      catheter days. In multiple logistic regression analysis, patients with
      bloodstream infection were more likely to have multiple central venous catheters
      (adjusted odds ratio [aOR]: 5.7; 95% confidence interval [CI]: 2.9-10.9),
      arterial catheters (aOR: 5.5; 95% CI: 1.8-16.3), invasive procedures performed in
      the PICU (aOR: 4.0; 95%CI: 2.0-7.8), and be transported out of the PICU (aOR:
      3.4; 95% CI: 1.8-6.7) to the radiology or operating room suites. Severity of
      illness as measured by admission Pediatric Risk of Mortality score, underlying
      illnesses, and medications were not associated with increased risk of nosocomial
      bloodstream infection. Conclusions This study identified a high rate of
      bloodstream infection among St Louis Children's Hospital PICU patients. Risk
      factors for bloodstream infection were related more to process of care than to
      severity of illness. Additional research is needed to develop interventions to
      reduce nosocomial bloodstream infections in children.

PMID- 12205249
TI  - Home visiting by paraprofessionals and by nurses: a randomized, controlled trial.
AB  - OBJECTIVE: To examine the effectiveness of home visiting by paraprofessionals and
      by nurses as separate means of improving maternal and child health when both
      types of visitors are trained in a program model that has demonstrated
      effectiveness when delivered by nurses. METHODS: A randomized, controlled trial
      was conducted in public- and private-care settings in Denver, Colorado. One
      thousand one hundred seventy-eight consecutive pregnant women with no previous
      live births who were eligible for Medicaid or who had no private health insurance
      were invited to participate. Seven hundred thirty-five women were randomized to
      control, paraprofessional, or nurse conditions. Nurses completed an average of
      6.5 home visits during pregnancy and 21 visits from birth to the children's
      second birthdays. Paraprofessionals completed an average of 6.3 home visits
      during pregnancy and 16 visits from birth to the children's second birthdays. The
      main outcomes consisted of changes in women's urine cotinine over the course of
      pregnancy; women's use of ancillary services during pregnancy; subsequent
      pregnancies and births, educational achievement, workforce participation, and use
      of welfare; mother-infant responsive interaction; families' home environments;
      infants' emotional vulnerability in response to fear stimuli and low emotional
      vitality in response to joy and anger stimuli; and children's language and mental
      development, temperament, and behavioral problems. RESULTS: Paraprofessional
      visited mother-child pairs in which the mother had low psychological resources
      interacted with one another more responsively than their control-group
      counterparts (99.45 vs 97.54 standard score points). There were no other
      statistically significant paraprofessional effects. In contrast to their control
      group counterparts, nurse-visited smokers had greater reductions in cotinine
      levels from intake to the end of pregnancy (259.0 vs 12.32 ng/mL); by the study
      child's second birthday, women visited by nurses had fewer subsequent pregnancies
      (29% vs 41%) and births (12% vs 19%); they delayed subsequent pregnancies for
      longer intervals; and during the second year after the birth of their first
      child, they worked more than women in the control group (6.83 vs 5.65 months).
      Nurse-visited mother-child pairs interacted with one another more responsively
      than those in the control group (100.31 vs 98.99 standard score points). At 6
      months of age, nurse-visited infants, in contrast to their control-group
      counterparts, were less likely to exhibit emotional vulnerability in response to
      fear stimuli (16% vs 25%) and nurse-visited infants born to women with low
      psychological resources were less likely to exhibit low emotional vitality in
      response to joy and anger stimuli (24% vs 40% and 13% vs 33%). At 21 months,
      nurse-visited children born to women with low psychological resources were less
      likely to exhibit language delays (7% vs 18%); and at 24 months, they exhibited
      superior mental development (90.18 vs 86.20 Mental Development Index scores) than
      their control-group counterparts. There were no statistically significant program
      effects for the nurses on women's use of ancillary prenatal services, educational
      achievement, use of welfare, or their children's temperament or behavior
      problems. For most outcomes on which either visitor produced significant effects,
      the paraprofessionals typically had effects that were about half the size of
      those produced by nurses. CONCLUSIONS: When trained in a model program of
      prenatal and infancy home visiting, paraprofessionals produced small effects that
      rarely achieved statistical or clinical significance; the absence of statistical
      significance for some outcomes is probably attributable to limited statistical
      power to detect small effects. Nurses produced significant effects on a wide
      range of maternal and child outcomes.

PMID- 12205250
TI  - A prospective study of the role of depression in the development and persistence
      of adolescent obesity.
AB  - BACKGROUND: Adolescent obesity is a strong predictor of adult obesity, and adult
      obesity has been associated with depression, especially in women. Studies have
      also suggested an association between depression in adolescence and higher body
      mass index (BMI) in adulthood. Whether depression leads to obesity or obesity
      causes depression is unclear. OBJECTIVE: To determine in longitudinal analyses
      whether depressed mood predicts the development and persistence of obesity in
      adolescents. METHODS: A prospective cohort study of 9374 adolescents in grades 7
      through 12 who completed in-home interviews for the National Longitudinal Study
      of Adolescent Health. Assessments were made at baseline (1995) and at follow-up 1
      year later. Depressed mood was assessed with the Center for Epidemiologic Studies
      Depression Scale. BMI (kg/m2) was calculated from self-reported height and
      weight. BMI percentiles and z scores were computed using the 2000 Centers for
      Disease Control and Prevention growth charts. Obesity was defined as BMI > or
      =95th percentile, overweight as BMI > or =85th percentile and <95th percentile,
      and normal weight as BMI <85th percentile. A parental respondent gave information
      on household income, parental education, and parental obesity. RESULTS: At
      baseline, 12.9% were overweight, 9.7% were obese, and 8.8% had depressed mood.
      Baseline depression was not significantly correlated with baseline obesity. Among
      the 9.7% who were obese at follow-up, 79.6% were obese at baseline, 18.6% were
      overweight at baseline, and 1.8% were normal weight at baseline. Having depressed
      mood at baseline independently predicted obesity at follow-up (odds ratio: 2.05;
      95% confidence interval: 1.18, 3.56) after controlling for BMI z score at
      baseline, age, race, gender, parental obesity, number of parents in the home, and
      family socioeconomic status. This finding persisted after controlling further for
      the adolescents' report of smoking, self-esteem, delinquent behavior (conduct
      disorder), and physical activity. After controlling for all these same factors,
      depressed mood at baseline also predicted obesity at follow-up among those not
      obese at baseline (odds ratio: 2.05; 95% confidence interval: 1.04, 4.06) and
      follow-up BMI z score among those obese at baseline (beta = 0.11; standard error
      beta = 0.05). In contrast, baseline obesity did not predict follow-up depression.
      CONCLUSIONS: Depressed adolescents are at increased risk for the development and
      persistence of obesity during adolescence. Understanding the shared biological
      and social determinants linking depressed mood and obesity may inform the
      prevention and treatment of both disorders.

PMID- 12205251
TI  - Television viewing and initiation of smoking among youth.
AB  - BACKGROUND: Smoking is the leading preventable cause of death in the United
      States, and the risk of disease increases the earlier in life smoking begins. The
      prevalence of smoking among US adolescents has increased since 1991. Despite bans
      on television tobacco advertising, smoking on television remains widespread.
      OBJECTIVE: To determine whether youth with greater exposure to television viewing
      exhibit higher rates of smoking initiation. METHODS: We used the National
      Longitudinal Survey of Youth, Child Cohort to examine longitudinally the
      association of television viewing in 1990 among youth ages 10 to 15 years with
      smoking initiation from 1990-1992. Television viewing was based on the average of
      youth and parent reports. We used multiple logistic regression, taking into
      account sampling weights, and controlled for ethnicity; maternal education, IQ,
      and work; household structure; number of children; household poverty; child
      gender; and child aptitude test scores. RESULTS: Among these youth, smoking
      increased from 4.8% in 1990 to 12.3% in 1992. Controlling for baseline
      characteristics, youth who watched 5 or more hours of TV per day were 5.99 times
      more likely to initiate smoking behaviors (95% confidence interval: 1.39-25.71)
      than those youth who watched <2 hours. Similarly, youth who watched >4 to 5 hours
      per day were 5.24 times more likely to initiate smoking than youth who watched <2
      hours (95% confidence interval: 1.19-23.10). CONCLUSIONS: Television viewing is
      associated in a dose-response relationship with the initiation of youth smoking.
      Television viewing should be included in adolescent risk behavior research.
      Interventions to reduce television viewing may also reduce youth smoking
      initiation.

PMID- 12205252
TI  - Parental screening for intimate partner violence by pediatricians and family
      physicians.
AB  - OBJECTIVE: To ascertain and compare the knowledge, practices, and training needs
      of pediatricians and family physicians regarding intimate partner violence
      screening and intervention. METHODS: Surveys were mailed to national random
      samples of 1350 pediatricians and 650 family physicians evenly divided between
      senior residents, practitioners completing their residency training within the
      last 5 years, and practitioners completing their training >5 years ago. RESULTS:
      The overall response rate was 37% (41% for pediatricians, 30% for family
      physicians). Among practicing physicians, only 8% of family physicians and 5% of
      pediatricians routinely screened a parent for intimate partner violence during
      well-child and teen visits. Family medicine residents were significantly more
      likely to routinely screen for intimate partner violence (18%), whereas pediatric
      residents were not (7%). All groups demonstrated deficits in knowledge of
      appropriate management of situations of domestic abuse; for example, over 60% of
      family medicine and 75% of pediatric residents and practitioners agreed with the
      inappropriate response of always urging a woman to leave her abusive partner
      immediately. Many physicians indicated a need for more information about domestic
      violence, ranging from 40% of family medicine residents to 72% of pediatric
      residents. Residency training and continuing medical education in the prevention
      of child/adolescent violence and having an office protocol for managing cases
      involving domestic violence increased the likelihood of parental screening for
      intimate partner violence. CONCLUSIONS: Few child and adolescent primary care
      physicians routinely screen parents for intimate partner violence and most need
      more information on this topic. Residency training and continuing medical
      education on violence prevention, including screening and intervention skills in
      intimate partner violence, and office protocols for managing cases of domestic
      violence could increase screening rates.

PMID- 12205253
TI  - Early introduction of oral feeding in preterm infants.
AB  - OBJECTIVE: To determine whether transition from tube to all oral feeding can be
      accelerated by the early introduction of oral feeding in preterm infants. It is
      hypothesized that this shortened transition time will lead to earlier attainment
      of all oral feeding. DESIGN: Twenty-nine infants (<30 weeks' gestation) were
      randomized to an intervention or control group. The intervention group (n = 13)
      was initiated to oral feeding 48 hours after achieving full tube feeding (120
      kcal/kg/d), and the feeding progression followed a structured protocol. The oral
      feeding management of the control infants (n = 16) was left to the discretion of
      their attending physicians. Oral feeding progress was monitored for achievement
      of selected feeding milestones: achievement of first and all successful oral
      feedings. Feeding performance was assessed by overall transfer (percent volume
      transferred during a feeding/total volume offered) and rate of milk transfer
      (mL/min), which were measured from introduction of oral feeding to first
      successful oral feeding. RESULTS: Infants in the experimental group, when
      compared with their control counterparts, were introduced to oral feeding
      significantly earlier (31.1 +/- 1.3 vs 33.7 +/- 0.9 weeks' postmenstrual age,
      respectively) and attained all oral feeding significantly earlier as well (34.5
      +/- 1.6 vs 36.0 +/- 1.5 weeks' postmenstrual age, respectively). The transition
      time from full tube feeding to all oral feeding was 26.8 +/- 12.3 days for the
      experimental group and 38.4 +/- 14.0 days for the control group. Both groups of
      infants demonstrated similar increase in overall transfer and rate of milk
      transfer from introduction of oral feeding until achievement of first successful
      oral feeding. CONCLUSIONS: Early introduction of oral feeding accelerates the
      transition time from tube to all oral feeding. This not only allows earlier
      attainment of all oral feeding, but it also provides practice opportunities that
      enhance the oral motor skills necessary for safe and successful feeding.

PMID- 12205254
TI  - Routine sucrose analgesia during the first week of life in neonates younger than
      31 weeks' postconceptional age.
AB  - OBJECTIVE: To determine the efficacy of sucrose analgesia for procedural pain
      during the first week of life in preterm neonates in neonatal intensive care
      units on enhancing later clinical outcomes. METHODS: A total of 107 preterm
      neonates who were born at <31 weeks' postconceptional age (PCA) entered this
      double-blind, randomized, controlled trial within 48 hours of birth at 3 level
      III university-affiliated neonatal intensive care units in Canada, and 103
      completed the study. Sucrose (0.1 mL of 24%) or sterile water was administered
      orally up to 3 times, 2 minutes apart, for every invasive procedure during a 7
      day period. Motor development and vigor, and alertness and orientation components
      of the Neurobehavioral Assessment of the Preterm Infant were measured at 32, 36,
      and 40 weeks' PCA; Score for Neonatal Acute Physiology was measured on the last
      day of intervention; and Neuro-Biological Risk Score (NBRS) was measured at 2
      weeks of age and at discharge. Primary analyses of covariance were applied for
      each outcome to compare group differences followed by secondary analyses using
      standard linear regression within each group to determine predictors of outcomes.
      RESULTS: Although there were no differences between the groups on any outcomes,
      there were significant dose-related effects within each group. In the sucrose
      group only, higher number of doses of sucrose predicted lower scores on motor
      development and vigor, and alertness and orientation at 36 weeks', lower motor
      development and vigor at 40 weeks', and higher NBRS at 2 weeks' postnatal age.
      Higher number of invasive procedures was predictive of higher NBRS both times in
      the water group. CONCLUSIONS: Repeated use of sucrose analgesia in infants <31
      weeks' PCA may put infants at risk for poorer neurobehavioral development and
      physiologic outcomes. Additional study is needed to determine the most
      appropriate age and duration of sucrose analgesia in preterm infants.

PMID- 12205255
TI  - Effects of volume-guaranteed synchronized intermittent mandatory ventilation in
      preterm infants recovering from respiratory failure.
AB  - OBJECTIVE: Volume guarantee (synchronized intermittent mandatory ventilation
      [SIMV]+VG) is a novel mode of SIMV for automatic adjustment of the peak
      inspiratory pressure to ensure a minimum set mechanical tidal volume (V(T mech)).
      The objective of this study was to compare the effects of SIMV+VG with
      conventional SIMV on ventilation and gas exchange in a group of very low birth
      weight infants recovering from acute respiratory failure. METHODS: Nine infants
      were initially studied during 2 consecutive 60-minute ventilatory modalities of
      conventional SIMV (ventilator settings by clinical team) and SIMV+VG 4.5 (V(T
      mech) set at 4.5 mL/kg) in random order. Eight additional infants were studied
      during the same ventilatory modalities plus 1 additional epoch consisting of
      SIMV+VG 3.0 (V(T mech) set at 3.0 mL/kg). RESULTS: Peak inspiratory pressure was
      significantly lower during SIMV+VG 3.0. Mean airway pressure, V(T mech), number
      of large V(T mech) (>7 mL/kg), and mechanical minute ventilation (V'(E)) were
      reduced during SIMV+VG 4.5 compared with SIMV and were further reduced during
      SIMV+VG 3.0. Spontaneous V'(E) increased during SIMV+VG 4.5 and was even higher
      during SIMV+VG 3.0. The resulting total V'(E) was higher during both SIMV+VG
      modes compared with SIMV. Arterial oxygen saturation by pulse oximetry,
      transcutaneous carbon dioxide tension, and fraction of inspired oxygen did not
      differ significantly, although transcutaneous carbon dioxide tension increased
      slightly during SIMV+VG 3.0. CONCLUSIONS: The short-term use of SIMV+VG resulted
      in automatic weaning of the mechanical support and enhancement of the spontaneous
      respiratory effort while maintaining gas exchange relatively unchanged in
      comparison to conventional SIMV.

PMID- 12205256
TI  - Free thyroxine levels during the first weeks of life and neurodevelopmental
      outcome until the age of 5 years in very preterm infants.
AB  - BACKGROUND: We have conducted a randomized trial with thyroxine (T4) in 200
      infants <30 weeks' gestation. T4 treatment was associated with better 5-year
      outcome in infants <29 weeks' gestation, but with worse outcome in infants of 29
      weeks. These effects could be related to low, respectively high free thyroxine
      (FT4) levels METHODS: For each infant, the average FT4 of 5 scheduled
      measurements was calculated between day 3 and day 28. Infants of the placebo and
      the T4 group separately were divided in 2 groups. The placebo group consisted of
      a group of infants with average FT4 in the lowest quartile and a group in the
      upper 75%. The T4 group consisted of a group of infants with average FT4 in the
      upper quartile and a group in the lower 75%. Developmental outcome
      (mental/cognitive, motor, and neurologic) at 2 and 5.7 years was compared between
      high and low FT4 groups, and then compared separately for the T4 and placebo
      group. RESULTS: In the placebo group, low FT4 was associated with worse outcome
      on all domains at both time points. After correction for confounding variables,
      mental and neurologic outcome remained significantly different at 2 years, and
      motor outcome at 5 years. In the T4 group, high FT4 was not associated with worse
      outcome, neither at 2 nor at 5 years. CONCLUSIONS: In untreated infants, low FT4
      values during the first 4 weeks after birth in infants born at <30 weeks'
      gestation are associated with worse neurodevelopmental outcome at 2 and 5 years.
      In T4-treated infants, high FT4 is not associated with worse outcome. Other
      factors than high FT4 concentrations must play a role in the worse outcome of the
      T4-treated group of 29 weeks' gestational age.

PMID- 12205257
TI  - Retinopathy of prematurity outcome in infants with prethreshold retinopathy of
      prematurity and oxygen saturation >94% in room air: the high oxygen percentage in
      retinopathy of prematurity study.
AB  - OBJECTIVES: To determine the rate of progression from prethreshold to threshold
      retinopathy of prematurity (ROP) in infants excluded from Supplemental
      Therapeutic Oxygen for Prethreshold Retinopathy of Prematurity (STOP-ROP) because
      their median arterial oxygen saturation by pulse oximetry (SpO2) values were >94%
      in room air at the time of prethreshold diagnosis and to compare them with
      infants who were enrolled in STOP-ROP and had median SpO2 < or =94% in room air.
      METHODS: Fifteen of the 30 centers that participated in STOP-ROP elected to
      participate in the High Oxygen Percentage in Retinopathy of Prematurity study
      (HOPE-ROP) from January 1996 to March 1999. Infants were followed prospectively
      from the time prethreshold ROP was diagnosed until ROP either progressed to
      threshold in at least 1 study eye (adverse outcome) or resolved (favorable
      outcome). RESULTS: A total of 136 HOPE-ROP infants were compared with 229 STOP
      ROP infants enrolled during the same time period from the same 15 hospitals. HOPE
      ROP infants were of greater gestational age at birth (26.2 +/- 1.8 vs 25.2 +/-
      1.4 weeks) and greater postmenstrual age at the time of prethreshold ROP
      diagnosis (36.7 +/- 2.5 vs 35.4 +/- 2.5 weeks). HOPE-ROP infants progressed to
      threshold ROP 25% of the time compared with 46% of STOP-ROP infants. After
      gestational age, race, postmenstrual age at prethreshold diagnosis, zone 1
      disease, and plus disease at prethreshold diagnosis were controlled for, logistic
      regression analysis showed that HOPE-ROP infants progressed from prethreshold to
      threshold ROP less often than STOP-ROP infants (odds ratio: 0.607; 95% confidence
      interval: 0.359-1.026). CONCLUSIONS: The mechanisms that result in better ROP
      outcome for HOPE-ROP versus STOP-ROP are not fully understood. It seems that an
      infant's SpO2 value at the time of prethreshold diagnosis is a prognostic
      indicator for which infants may progress to severe ROP. When other known
      prognostic indicators are factored in, the SpO2 is of borderline significance.

PMID- 12205258
TI  - Sex differences in iron status during infancy.
AB  - BACKGROUND: It is commonly assumed that there is no difference in iron status
      between male and female infants, despite a lack of studies addressing this
      question. OBJECTIVE: To study sex differences in different measures of iron
      status in infants. METHODS: At 4 months of age, 263 term, breastfed infants (121
      Swedish and 142 Honduran) were randomized to receive iron supplements or placebo
      until 9 months of age. Blood samples at 4, 6, and 9 months of age were analyzed
      for hemoglobin (Hb), mean cell volume (MCV), zinc protoporphyrin (ZPP), plasma
      ferritin, and transferrin receptors (TfR). RESULTS: At 4, 6, and 9 months, boys
      had significantly lower Hb, MCV, and ferritin and higher ZPP and TfR than girls.
      At 9 months, boys had a 10-fold higher risk of being classified as having iron
      deficiency anemia. The differences at 9 months in MCV (71.6 vs 75.1 fL) and ZPP
      (59 vs 49 micro mol/mol heme) remained significant after controlling for iron
      supplementation, site, growth variables, and other possible confounders. For
      ferritin, there was a remaining sex difference at 9 months among Swedish (29 vs
      53 micro g/L) but not Honduran infants. For Hb and TfR, sex differences at 9
      months were larger in unsupplemented infants, especially in those with a birth
      weight of <3500 g. CONCLUSIONS: There are substantial sex differences in Hb and
      other indicators of iron status during infancy. Some of these may be genetically
      determined, whereas others seem to reflect an increased incidence of true iron
      deficiency in boys.

PMID- 12205259
TI  - Comparison of oral versus normal and high-dose rectal acetaminophen in the
      treatment of febrile children.
AB  - OBJECTIVES: To compare the defervescent effect of high-dose rectal suppository
      acetaminophen with the recommended oral and rectal dosages and to evaluate
      acceptability of rectal acetaminophen. METHODS: A randomized, controlled trial
      was performed in 70 patients aged 6 months to 6 years with fever > or =39 degrees
      C. Group A received rectal acetaminophen 15 mg/kg, group B received rectal
      acetaminophen 30 mg/kg, and group C received oral acetaminophen 15 mg/kg. Primary
      outcome was maximal change in temperature during the 3-hour study period after
      initial treatment. RESULTS: There were 24 patients in group A, 23 in group B, and
      23 in group C. There was no significant difference in temperature change between
      the groups during the 3 hours or in the maximum drop in temperature or final
      temperature. Visual analog scores for satisfaction of parents did not reveal any
      significant differences between the oral and rectal routes. CONCLUSIONS: There
      was no difference between the temperature decrement in patients treated with 15
      mg/kg oral acetaminophen and the same or double dose rectally. Thus, there seems
      to be no evidence to support the use of higher doses of rectal acetaminophen for
      the treatment of fever in children. The rectal route proved to be as acceptable
      as the oral among parents.

PMID- 12205260
TI  - Prevalence of retinal hemorrhages and child abuse in children who present with an
      apparent life-threatening event.
AB  - OBJECTIVE: Child abuse (CA) can present with a spectrum of signs and symptoms.
      Apparent life-threatening events (ALTEs) may be a subtle presentation of CA.
      Retinal hemorrhages (RHs) are a well-described finding in some patients with CA.
      We hypothesized that screening children who present with a chief complaint of an
      ALTE for RH would detect an otherwise occult presentation of CA. METHODS:
      Children who were younger than 24 months of age and presented to the emergency
      department between March 1, 1997, and February 28, 1999, with signs and symptoms
      consistent with the National Institutes of Health's definition of an ALTE were
      studied prospectively. Children were excluded when it was readily apparent on
      presentation that the child was a victim of CA. Demographic data, a complete
      blood count with differential, venous blood gas, carboxyhemoglobin level, and
      urine toxicological screen were collected. A pediatric ophthalmologist performed
      a dilated funduscopic examination; patients who were found to have RH underwent a
      noncontrast computerized tomographic scan of the head and skeletal survey to
      evaluate for occult injury. Evaluations by social services or Children, Youth and
      Families, the results of all diagnostic tests obtained, and the final discharge
      diagnosis were recorded. Medical records of all patients were reviewed at 1 year;
      subsequent visits, hospitalizations, and evaluations by social services or
      Children, Youth and Families were recorded. RESULTS: A total of 128 patients
      presented to the emergency department with an ALTE during the study period. No
      patients were excluded. Mean age was 2.1 months (median: 1.27; range: 0.07-16.0;
      standard deviation: 2.1). Fifty-seven (44.5%) were boys; 86 (67.2%) were white,
      and 36 (27.9%) were black. A total of 26 (20.3%) of 128 patients had a history of
      an ALTE, 4 (3.4%) of 117 had a family history of an ALTE, and 15 (12.8%) of 117
      had a family history of sudden infant death syndrome. Dilated funduscopic
      examination was performed on 73 (57.0%) of 128 patients; RH was detected in 1
      patient (1.4%). Four children, including the patient with RH, underwent an
      evaluation for suspected abuse; 3 (2.3%) of 128 were determined to have been
      abused. CONCLUSIONS: RH was detected in 1 (1.4%) of 73 patients in our population
      of infants with ALTEs and 1 of 3 patients who were victims of CA and presented
      with an ALTE. CA was detected in 2.3% of patients who presented with an ALTE. The
      diagnosis of CA should be seriously considered in patients who present with an
      ALTE. The evaluation of ALTEs should include funduscopic examination as ALTEs and
      RHs are associated with CA.

PMID- 12205261
TI  - Assessment of adrenal function in the initial phase of meningococcal disease.
AB  - OBJECTIVE: To determine the status of the hypothalamic-pituitary-adrenal axis in
      children who had meningococcal disease and were admitted to 2 regional pediatric
      intensive care units. METHODS: Sixty-five children (34 boys; median age: 2.5
      years; range: 0.2-15 years) had cortisol and adrenocorticotropic hormone (ACTH)
      levels measured on admission, then at 8 AM and 8 PM during the next 48 hours. At
      48 hours, a low-dose short Synacthen test (LDST) (500 ng of 1-24
      corticotropin/m2) was performed in 42 patients (19 boys). Normal ranges for 8 AM
      cortisol and ACTH levels in unstressed children were 140 to 500 nmol/L and 2 to
      11.3 pmol/L, respectively. Adrenal insufficiency (AI) was defined as a peak
      cortisol <500 nmol/L on the LDST or an 8 AM cortisol value <140 nmol/L. RESULTS:
      Five (7.7%) of the 65 children died, including 1 with primary AI. Cortisol levels
      were elevated on admission (median: 1122 mmol/L; range: 65-2110 nmol/L) with 81%
      of values more than the 8 AM normal range. The median ACTH level on admission was
      within the 8 AM normal range, but 40% of values were more than the 8 AM normal
      range. However, 7% and 8% of cortisol and ACTH values, respectively, were less
      than the normal range. Both cortisol and ACTH levels fell thereafter and showed
      no diurnal variation during the 48-hour profile. Six (14%) of the 42 failed the
      LDST. These patients had significantly lower mean 8 AM cortisol values than those
      with a normal peak value on the LDST. Five additional patients who did not have
      the LDST had 8 AM cortisol values <140 nmol/L. In the diagnosis of AI, the
      sensitivity of the 8 AM mean cortisol value at a cutoff of 400 nmol/L, judged
      against the LDST, was 83%; the specificity was 81%. CONCLUSIONS: During the
      initial phase of meningococcal disease, raised cortisol and ACTH levels indicate
      an appropriate stress response within the hypothalamic-pituitary-adrenal axis.
      However, a substantial subpopulation (11 [16.9%] of 65) has evidence of adrenal
      dysfunction during this period. Morning cortisol values in the initial phase of
      meningococcal disease could be used as a potential early index of AI.

PMID- 12205262
TI  - Does parenchymal brain injury affect biobehavioral pain responses in very low
      birth weight infants at 32 weeks' postconceptional age?
AB  - OBJECTIVE: Children with neurologic impairments have shown diminished pain
      response compared with control subjects; however, it remains unclear what
      mechanisms underlie this response or when it develops. If this were also true
      with premature infants who undergo neonatal intensive care, then infants with
      parenchymal brain injury (PBI) would be at increased risk of underrecognition and
      undertreatment of procedural pain. The purpose of this study was to determine
      whether infants with PBI display altered responses to acute procedural pain at 32
      weeks' postconceptional age (PCA), compared with control subjects. METHODS: We
      compared responses to blood collection by heel lance at 32 weeks' PCA in 12 very
      low birth weight infants (mean [range] birth weight: 876 g [630-1240 g];
      gestational age: 26.3 weeks (24-28 weeks) who had sustained PBI in the neonatal
      period, with 12 control subjects matched for gestational age at birth and gender
      (838 g [625-990 g]; 26.3 weeks [24-28 weeks[) who had normal neonatal brain
      imaging. PBI was defined as cerebral parenchymal infarction (grade 4
      intraventricular hemorrhage) or cystic periventricular leukomalacia on serial
      cranial ultrasound scans conducted in the neonatal period. Biobehavioral
      responses to pain were measured using facial activity (Neonatal Facial Coding
      System) and measures of heart rate (HR) variability (low-frequency [LF] power
      [0.04-0.15], high-frequency [HF] power [0.15-0.8 Hz], and LF/HF ratio) as a
      measure of cardiac autonomic modulation. Neurodevelopmental follow-up was
      undertaken at 18 months. RESULTS: The infants with PBI had significantly higher
      illness severity scores at day 1 compared with day 3 (Score of Neonatal Acute
      Physiology II: 32.1 vs 19.8) but similar previous pain experiences (109 vs 115)
      and total morphine exposure (0.29 vs 0.30 mg/kg). Both groups of children mounted
      similar responses to heel lance at 32 weeks' PCA with no difference in facial
      response or HR variability. Mean HR and facial action scores increased from
      baseline to the lance, whereas LF, HF, and the LF/HF ratio decreased
      significantly. No group differences were found. The only statistically
      significant difference between groups was that infants with PBI had more tongue
      protrusion at lance. Neurodevelopmental follow-up showed 8 of 11 toddlers with
      PBI had cerebral palsy compared with 0% of control toddlers. Psychomotor
      Developmental Index score on the Bayley Scales of Infant Development II was
      significantly lower in the PBI group. Five of 11 toddlers with PBI had Mental
      Developmental Index score <2 standard deviations below mean compared with 0% of
      the control toddlers. CONCLUSION: Contrary to expectations, we did not find any
      evidence of an altered pain response pattern in infants with proven brain injury
      in the neonatal period. Although most infants with PBI developed cerebral palsy,
      these findings suggest that cerebral injury predominantly to the central white
      matter leaves brainstem responses intact in the neonatal period. Furthermore, it
      seems that the injured brain of the preterm infant has not yet expressed the
      identifiable differences in pain display and the functional impairment observed
      at later ages.

PMID- 12205263
TI  - National practices regarding payment to research subjects for participating in
      pediatric research.
AB  - OBJECTIVE: Payment to subjects for participation in research is reportedly
      common, but no published data documents the nature of this practice.
      Institutional review boards (IRBs) are responsible for ensuring both the safety
      and voluntary participation of research subjects, yet guidance from federal and
      expert pediatric sources regarding appropriate payment approaches is conflicting.
      Ethical issues of payment for participation of adult versus pediatric research
      subjects may differ. This empirical study sought to examine current payment
      practices for participation in pediatric research as reported by IRBs. DESIGN: An
      18-question survey regarding payment practices for participation in pediatric
      research was sent to IRB chairs at member institutions of the National
      Association of Children's Hospitals and Related Institutions, and to a systematic
      random sample of IRB chairs listed with the Office for Protection From Research
      Risks. Descriptive, nonparametric, and qualitative analyses were used to describe
      institution types, payment practices, and correlations among responses. RESULTS:
      Data from 128 institutions that conduct pediatric research revealed that payment
      for participation in pediatric research was allowed by 66% of responding
      institutions, and practices varied widely among institutions. Most responding
      IRBs that allowed payment required disclosure of payment before enrollment
      (during the consent process), following federal guidelines more closely than
      American Academy of Pediatrics guidelines. An IRB's perception of potential
      benefits or harms of a study correlated with the amount of payment approved.
      CONCLUSIONS: IRBs must balance the need to recruit pediatric research subjects
      against the risk of undue influence during the recruitment process. Federal
      guidelines and expert pediatric opinion differ in recommendations regarding
      payment; responding IRBs appeared to follow federal guidelines more closely than
      guidelines proposed by the American Academy of Pediatrics.

PMID- 12205264
TI  - Adult survivors of pediatric illness: the impact on pediatric hospitals.
AB  - CONTEXT: Patients now live well into adulthood surviving diseases with pediatric
      onset. The size and financial impact of this growing population is unknown.
      OBJECTIVE: To describe the demographics of adult inpatients in pediatric
      facilities and to assess the financial impact of providing care for these
      patients on freestanding children's hospitals. DESIGN AND DATA SOURCES: An
      observational study using the Pediatric Health Information System, a proprietary
      database available to Child Health Corporation of America member hospitals,
      covering years 1994-1999. These data reflect inpatient services and exclude
      outpatient encounters and adult patients transitioned to adult providers.
      National estimates of the number of adult survivors of pediatric illness and the
      financial impact of care were calculated. Hospitals with >100 discharge events
      for patients > or =age 21 in 1999, and having both clinical and financial data in
      the dataset, assured an adequate sample size to discern resource utilization.
      Both 18 and 21 were used as lower limits of adult age to reflect common
      definitions of legal majority (age 18) and common pediatric practice (age 21). We
      truncated the data at age 64 to exclude patients eligible for Medicare. RESULTS:
      Ten hospitals representing all geographic regions of the United States were used
      for an in-depth analysis of financial impact during 1999. Six of 10 had data for
      1994-1999 to describe trends over time. The number of patients admitted over the
      6-year period increased, as did average and total adjusted charges. In 1999, 3863
      patients 18 to 64 years old incurred 5051 discharge episodes and total charges of
      $134.5 million. Of these, about half (1785) were > or =21 with charges of $66
      million. Of the hospitals' total discharges and financial charges, on average
      2.1% and 3.1%, respectively, were from the inpatient care of patients 21 to 64
      years old. Forty percent of patients receive public aid. Extrapolating from
      census data, up to 15 000 patients > or =21 years annually may seek inpatient
      care in part at children's hospitals, with charges exceeding $500 million. The 3
      most common diagnostic groups to be admitted were those with cystic fibrosis,
      mental retardation or cerebral palsy, and congenital heart disease. CONCLUSIONS:
      We describe a subset of adults who have survived diseases of pediatric onset. We
      focused on the portion of that population that obtains at least some inpatient
      care at a children's hospital. The data reported here can be used to set a lower
      boundary for the size of this population, and thereby provide valuable data for
      health planners as well as clinicians. If one includes estimates of expenses
      across the continuum of care, the financial impact of this growing population is
      substantial. Public policy discussions should include the medical, psychological,
      social, and financial needs of this population.

PMID- 12205265
TI  - Survival in early- and late-term infants with congenital diaphragmatic hernia
      treated with extracorporeal membrane oxygenation.
AB  - BACKGROUND: Congenital diaphragmatic hernia (CDH) is a malformation of the
      diaphragm that allows bowel to enter the thoracic cavity, resulting in pulmonary
      hypoplasia and pulmonary hypertension. Approximately 50% of CDH patients are
      treated with extracorporeal membrane oxygenation (ECMO). The optimal gestational
      age for delivery of term infants with CDH at high risk for requiring ECMO is not
      known. The goal of this study was to compare survival of infants with CDH
      receiving ECMO born early term (38 0/7-39 6/7 weeks' gestation) with those born
      late term (40 0/7-41 6/7 weeks' gestation). Changes in survival rates of term
      infants and the factors associated with these changes were assessed over the 25
      years that ECMO has been available. METHODS:  DESIGN: Retrospective cohort study
      of infants with CDH treated with ECMO. DATA SOURCES: The Extracorporeal Life
      Support Organization registry of patients treated at active Extracorporeal Life
      Support Organization centers from April 1976 through June 2001. ANALYSIS:
      Survival and clinical predictors of survival were compared between infants born
      early term (38 0/7-39 6/7 weeks' gestation) and infants born late term (40 0/7-41
      6/7 weeks' gestation). Changes in survival rates over time and factors associated
      with survival were evaluated. RESULTS: Among full-term infants with CDH treated
      with ECMO, late-term compared with early-term delivery was associated with
      improved survival (63% vs 53%). Among full-term survivors of ECMO, late-term
      infants spent less time on ECMO (181 vs 197 hours) and less time in the hospital
      (60 vs 67 days). In multivariate analysis, greater birth weight, higher 5-minute
      Apgar score, higher arterial pH and PCO(2) <50 torr before ECMO, and absence of a
      prenatal diagnosis of CDH were associated with survival. Since the late 1980s,
      survival of infants with CDH requiring ECMO decreased from 63% to 52%. The
      decreased survival rate was associated with increased rates of prenatal
      diagnosis, early-term delivery, lower birth weight, longer ECMO runs, and more
      frequent complications on ECMO. CONCLUSIONS: Among term infants with CDH
      receiving ECMO, late-term delivery compared with early-term delivery is
      associated with improved survival, shorter ECMO duration, shorter hospital length
      of stay, and fewer complications on ECMO. These data suggest that, at least for
      the approximately 50% of CDH patients treated with ECMO, outcomes for infants
      with CDH may be improved by delay of elective delivery until 40 completed weeks
      of gestation.

PMID- 12205266
TI  - Infant feeding and blood cholesterol: a study in adolescents and a systematic
      review.
AB  - OBJECTIVE: To examine the influence of infant feeding method on serum total
      cholesterol (TC) and low-density lipoprotein (LDL) cholesterol. METHODS: A cross
      sectional study of 13- to 16-year-olds and a systematic review of studies (all
      observational) on the effects of infant feeding on cholesterol in infancy (<1
      year), childhood or adolescence (1-16 years), and adulthood (> or =17 years) were
      conducted using random effects models. Differences are presented as breastfed
      bottle-fed. A total of 1532 individuals (92% white; 55% male; mean age: 15.1
      years) in 10 British towns were studied, and 37 studies with 52 observations on
      TC (26 in infancy, 17 in childhood or adolescence, and 9 in adulthood;
      corresponding figures for LDL were 7, 4, and 6) were reviewed. RESULTS: Mean TC
      in childhood or adolescence (including the new study) was not related to infant
      feeding pattern (mean TC difference = 0.00; 95% confidence interval [CI]: -0.07
      to 0.07 mmol/L). However, in infancy, mean TC was higher among those breastfed
      (mean TC difference = 0.64; 95% CI: 0.50-0.79 mmol/L), whereas in adults, mean TC
      was lower among those breastfed (mean TC difference = -0.18; 95% CI: -0.30 to 
      0.06 mmol/L). Patterns for LDL were similar to those for TC throughout.
      CONCLUSIONS: Breastfeeding is associated with increased mean TC and LDL levels in
      infancy but lower levels in adulthood/adult life. These results suggest that
      breastfeeding may have long-term benefits for cardiovascular health and may have
      implications for the content of formula feed milks.

PMID- 12205267
TI  - Oxygen therapy: 50 years of uncertainty.

PMID- 12205268
TI  - Intersex issues: a series of continuing conundrums.

PMID- 12205269
TI  - Abraham Morris Rudolph: an appreciation.
AB  - Dr Abraham Rudolph is one of the most distinguished pediatric cardiologists in
      the world. He entered pediatric cardiology (almost by accident) when the subject
      was still in its infancy and was present at--and indeed contributed to--most of
      its advances. He is best known for his studies on the pathophysiology of
      congenital heart diseases and for imaginative studies of fetal cardiovascular
      development and the transition to postnatal life.

PMID- 12205270
TI  - Clinical profile of 30 infants with acute pulmonary hemorrhage in Cleveland.
AB  - Between 1993 and 2000, 30 infants were hospitalized with acute pulmonary
      hemorrhage at Rainbow Babies and Children's Hospital in Cleveland. Most infants
      presented with severe pulmonary symptoms requiring intensive support, but a few
      infants had less severe hemorrhage. Three quarters of the patients required
      ventilator support and blood transfusions. Eleven patients had transitory
      hemoglobinuria. Five patients died, but infants who survived did well. There are
      currently no specific treatment modalities, although we have advised moving to a
      different home and avoiding environmental tobacco smoke. Subsequently, rebleeding
      from the lower respiratory tract has decreased from 5 of 7 infants to 1 in 21. On
      the basis of decreased subsequent fatal hemorrhage, high dose glucocorticoids
      seem to be of some value. Several patients revealed continued low-grade alveolar
      hemorrhage for months after their initial bleed, even after removal from their
      original home environments.

PMID- 12205271
TI  - Head lice.
AB  - Head lice infestation is associated with little morbidity but causes a high level
      of anxiety among parents of school-aged children. This statement attempts to
      clarify issues of diagnosis and treatment of head lice and makes recommendations
      for dealing with head lice in the school setting.

PMID- 12205272
TI  - When inflicted skin injuries constitute child abuse.
AB  - Child abuse should be considered as the most likely explanation for inflicted
      skin injuries if they are nonaccidental and there is any injury beyond temporary
      reddening of the skin. Minor forms of abuse may lead to severe abuse unless
      abusive skin injuries are identified and labeled as such and interventions are
      made.

PMID- 12205273
TI  - Acetaminophen recommendation.

PMID- 12205274
TI  - Pediatric career choices.

PMID- 12205275
TI  - Closing the "ductal connection"--the diabetes insipidus way.

PMID- 12205276
TI  - Too many vaccinations?

PMID- 12205277
TI  - Centers for Disease Control and Prevention growth charts versus breastfeeding?

PMID- 12205278
TI  - Survey of the injury rate for children in community sports.
AB  - OBJECTIVE: To determine the baseline injury rate for children ages 7 to 13
      participating in community organized baseball, softball, soccer, and football.
      METHODS: In this observational cohort study, 1659 children were observed during 2
      seasons of sports participation in an urban area. Data were collected by coaches
      using an injury survey tool designed for the study. A reportable injury was
      defined as one requiring on-field evaluation by coaching staff, or causing a
      player to stop participation for any period of time, or requiring first aid
      during an event. Logistic regression analyses were done within and across sports
      for injury rates, game versus practice injury frequencies, and gender differences
      where appropriate. RESULTS: The injury rates, calculated per 100 athlete
      exposures during total events (games plus practices), were: baseball, 1.7;
      softball, 1.0; soccer, 2.1; and football, 1.5. The injury rates for baseball and
      football were not significantly different. Across sports, contusions were the
      most frequent type of injury. Contact with equipment was the most frequent method
      of injury, except in football where contact with another player was the most
      frequent method. In baseball, 3% of all injuries reported were considered serious
      (fracture, dislocation, concussion); in soccer, 1% were considered serious; and
      in football, 14% were considered serious. The frequency of injury per team per
      season (FITS), an estimation of injury risk, was 3 for baseball and soccer, 2 for
      softball, and 14 for football for total events. For all sports, there were more
      game than practice injuries; this difference was significant except for softball.
      There were no significant gender differences in soccer for injury rates during
      total events. CONCLUSIONS: Given the classification of football as a collision
      sport, the high number of exposures per player, the FITS score, and the
      percentage of injuries considered serious, youth football should be a priority
      for injury studies. Health professionals should establish uniform medical
      coverage policies for football even at this age level. RECOMMENDATIONS FOR
      MODIFICATIONS: Injury surveillance for youth sports is gaining momentum as an
      important step toward formulating injury prevention methods. However,
      establishing patterns of injuries, taking preventive measures, and evaluating
      equipment and coaching modifications may take years. In addition to the objective
      findings of this study, our direct observations of community sports through 2
      seasons showed areas where immediate modifications could reduce injury risk. The
      first recommendation is that youth sports leagues provide and require first aid
      training for coaches. Training could be done by sports medicine professionals and
      include recognition and immediate response to head, neck, and spine injuries, as
      well as heat-related illnesses. The second recommendation is that youth sports
      leagues have clear, enforceable return to play guidelines for concussions, neck
      and back injuries, fractures, and dislocations. The third recommendation is that
      baseball and softball leagues consider the injury prevention potential of face
      guards on batting helmets.

PMID- 12205279
TI  - Distribution and correlates of non-high-density lipoprotein cholesterol in
      children: the Bogalusa Heart Study.
AB  - OBJECTIVE: Serum non-high-density lipoprotein (HDL) cholesterol (total
      cholesterol minus HDL cholesterol) is considered a better screening tool than low
      density lipoprotein (LDL) cholesterol for the assessment of coronary artery
      disease (CAD) risk in adults because it includes all classes of atherogenic
      lipoproteins. Although population frequency distribution and clinically useful
      cutpoints for this variable in adults have been reported recently, such
      information is lacking in children. Therefore, this study sought to provide
      population-based data on the distribution and correlates of non-HDL cholesterol
      in biracial (black-white) children. METHODS: The study sample consisted of 2843 5
      to 17-year-olds (57% white, 50% female) who participated in a cross-sectional
      screening of cardiovascular risk factors as part of the Bogalusa Heart Study.
      RESULTS: Non-HDL cholesterol levels were similar in black and white children, and
      higher in girls than in boys, especially among the younger (5-11 years) age
      group. Age was inversely related to both non-HDL cholesterol and LDL cholesterol.
      Body fatness as measured by body mass index and waist circumference was
      positively associated with non-HDL cholesterol. The magnitude of correlation with
      triglycerides was relatively higher for non-HDL cholesterol versus LDL
      cholesterol. Non-HDL cholesterol showed an inverse relation to HDL cholesterol.
      In a multivariate analysis, body mass index, age, gender, waist circumference,
      and cigarette smoking accounted for 7.7% of the variance in non-HDL cholesterol.
      Non-HDL cholesterol levels equivalent to currently recommended LDL cutpoints
      (110, 130, 160, and 190 mg/dL) for CAD risk assessment were 123, 144, 176, and
      207 mg/dL. CONCLUSION: Population-based data on non-HDL cholesterol are now
      available for children, which may help improve the CAD risk assessment and
      intervention.

PMID- 12205280
TI  - Birth weight and hearing impairment in norwegians born from 1967 to 1993.
AB  - OBJECTIVES: To estimate the association between birth weight and hearing
      impairment among Norwegians born between 1967 and 1993, taking other pregnancy
      related conditions into consideration. METHODS: A cohort study was conducted of
      all Norwegian live births from 1967 to 1993 (n = 1 548 429) linking information
      of the Medical Birth Registry of Norway and the register for the National
      Insurance Administration, which covers all Norwegians. The Medical Birth Registry
      of Norway has recorded information on birth weight and other pregnancy-related
      conditions as well as diseases of the mother before and during pregnancy. The
      register of the National Insurance Administration contains information on all
      Norwegians who have received cash benefits for a disease/disability, including
      hearing impairment. Data up to 1997 are included; thus, the follow-up period
      varies between 29 and 3 years. RESULTS: The occurrence of hearing impairment was
      11 per 10 000, decreasing from 60 per 10 000 for birth weights <1500 g to 6 per
      10 000 for birth weights >4499 g. Compared with birth weights between 3000 g and
      3499 g, the adjusted rate ratio of hearing impairment was 7.55 (95% confidence
      interval: 4.81-11.87) for birth weights <1500 g and 0.50 (95% confidence
      interval: 0.34-0.73) for birth weights >4499 g. The association did not change
      substantially with adjustment for other pregnancy-related conditions. Restricting
      the analyses to term born, the association between hearing impairment and low
      birth weight became stronger. CONCLUSIONS: Birth weight was a strong predictor of
      hearing impairment in the Norwegian population. Children who were born at term
      with a low birth weight seemed to be a particularly vulnerable group.

PMID- 12205281
TI  - Ambiguous genitalia with perineoscrotal hypospadias in 46,XY individuals: long
      term medical, surgical, and psychosexual outcome.
AB  - OBJECTIVES: To identify and study adults (21 years or older) who have a 46,XY
      karyotype and presented as infants or children with genital ambiguity, including
      a small phallus and perineoscrotal hypospadias, reared male or female. METHODS:
      Participants were classified according to the cause underlying their intersex
      condition based on review of medical and surgical records. Long-term medical and
      surgical outcome was assessed with a written questionnaire and physical
      examination. Long-term psychosexual development was assessed with a written
      questionnaire and semistructured interview. RESULTS: Thirty-nine (72%) of 54
      eligible patients participated. The cause underlying genital ambiguity of
      participants included partial androgen insensitivity syndrome (n = 14; 5 men and
      9 women), partial gonadal dysgenesis (n = 11; 7 men and 4 women), and other
      intersex conditions. Men had significantly more genital surgeries (mean: 5.8)
      than women (mean: 2.1), and physician-rated cosmetic appearance of the genitalia
      was significantly worse for men than for women. The majority of participants were
      satisfied with their body image, and men and women did not differ on this
      measure. Most men (90%) and women (83%) had sexual experience with a partner. Men
      and women did not differ in their satisfaction with their sexual function. The
      majority of participants were exclusively heterosexual, and men considered
      themselves to be masculine and women considered themselves to be feminine.
      Finally, 23% of participants (5 men and 4 women) were dissatisfied with their sex
      of rearing determined by their parents and physicians. CONCLUSIONS: Either male
      or female sex of rearing can lead to successful long-term outcome for the
      majority of cases of severe genital ambiguity in 46,XY individuals. We discuss
      factors that should be considered by parents and physicians when deciding on a
      sex of rearing for such infants.

PMID- 12205282
TI  - 46,XY intersex individuals: phenotypic and etiologic classification, knowledge of
      condition, and satisfaction with knowledge in adulthood.
AB  - OBJECTIVES: The objective of this study was to identify and study adults who have
      a 46,XY karyotype and presented as infants or children with variable degrees of
      undermasculinization of their genitalia (female genitalia, ambiguous genitalia,
      or micropenis). Participants' knowledge of their condition, satisfaction with
      their knowledge, and desire for additional education about their intersex
      condition were assessed. METHODS: Participants were classified according to the
      cause underlying their intersex condition based on review of medical and surgical
      records. Knowledge of medical condition, satisfaction with that knowledge, and
      desire for additional education were assessed with a written questionnaire and a
      semistructured interview. RESULTS: Patients were ineligible for recruitment
      because of death (9%), because of developmental delay (12%), or because they were
      not located (27%). Among the 96 eligible patients, 78% participated.
      Approximately half of the men (53%) and women (54%) exhibited a good
      understanding of their history. Fewer women who have a 46,XY chromosome
      complement and were born with female genitalia were informed about their intersex
      condition (36% with complete androgen insensitivity syndrome) than were women who
      were born with masculinized genitalia such as micropenis (80%) or ambiguous
      genitalia (72%). More women (66%) than men (38%) were satisfied with their
      knowledge of their medical and surgical history. CONCLUSIONS: Almost half of the
      patients, reared male or female, were neither well informed about their medical
      and surgical history nor satisfied with their knowledge.

PMID- 12205283
TI  - Validation of 2 pain scales for use in the pediatric emergency department.
AB  - OBJECTIVE: To determine the construct, content, and convergent validity of 2 self
      report pain scales for use in the untrained child in the emergency department
      (ED). METHODS: A prospective study was conducted of all children who presented to
      an urban ED between 5 and 16 years of age inclusive after written informed
      consent was obtained. Children were excluded if they were intoxicated, had
      altered sensorium, were clinically unstable, did not speak English, or had
      developmental delays. Children marked their current pain severity on a
      standardized Color Analog Scale (CAS) and a 7-point Faces Pain Scale (FPS). They
      were then asked whether their pain was mild, moderate, or severe. Children were
      then administered an analgesic at the discretion of the attending physician and
      asked to repeat these measurements. For assessing content validity, the scales
      were also administered to age- and gender-matched children in the ED for
      nonpainful conditions. Convergent validity was assessed by determining the
      Spearman correlation coefficient between the 2 pain scales. RESULTS: A total of
      60 children were enrolled, 30 with pain and 30 without, with a mean age of 9.3 +/
      3.3 years. Boys accounted for 38 of the enrollees (63.3%). The median score
      before analgesic administration was 6.0 cm (interquartile range [IQR]: 4.0-8.0)
      on the CAS and 3.0 faces (IQR: 2.0-5.0) on the FPS; after analgesic
      administration, the median scores decreased to 3.1 cm (IQR: 1.1-4.3) and 2.0
      faces (IQR: 1.0-3.0), respectively. As the reported pain intensity increased, so
      did the scores on the 2 pain scales. The 30 children with no pain had a median
      score on the CAS of 0.0 (IQR: 0.0-1.0) and on the FPS of 0.0 (IQR: 0.0-1.0),
      whereas the 13 children with severe pain had a median CAS of 7.0 (IQR: 6.0-8.0)
      and a median FPS of 5.0 (IQR: 4.0-6.0). The Spearman correlation coefficient
      between the CAS and the FPS was positive and strong (r = 0.894). CONCLUSION: The
      CAS and the FPS exhibit construct, content, and convergent validity in the
      measurement of acute pain in children in the ED.

PMID- 12205284
TI  - Long-term safety and efficacy of risperidone for the treatment of disruptive
      behavior disorders in children with subaverage IQs.
AB  - OBJECTIVE: The objective of this study was to investigate the long-term safety
      and efficacy of risperidone in disruptive behavior disorders in children with
      subaverage IQs. Disruptive behavior disorders were defined as oppositional
      defiant disorder, disruptive behavior disorder, and conduct disorder as per the
      Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV)
      criteria. METHODS: This was a 48-week open-label (OL) extension study of
      risperidone in 77 children diagnosed with a disruptive behavior disorder, and
      either borderline intellectual function or mild or moderate mental retardation
      who had participated in a previous 6-week, double-blind (DB) study and completed
      at least 2 weeks of DB therapy. Children, aged 5 to 12 years inclusive, who had:
      1) a DSM-IV Axis I diagnosis of conduct disorder, oppositional defiant disorder,
      or disruptive behavior disorder- not otherwise specified; 2) a parent-assessed
      rating of > or =24 in the Conduct Problem Subscale of the Nisonger-Child Behavior
      Rating Form(28); 3) a DSM-IV Axis II diagnosis of mild or moderate mental
      retardation or borderline intellectual functioning with an IQ > or =36 and < or
      =84; and 4) a score of < or =84 on the Vineland Adaptive Behavior Scale.
      Participants received oral solution risperidone given at a once daily dose of
      between 0.02 and 0.06 mg/kg for a maximum of 48 weeks. Participants in the DB
      study who had been randomized would have had a maximum of 54 weeks of risperidone
      therapy. Study visits were scheduled at entry, weekly for the first month, and
      monthly for the remaining 11 months. RESULTS: Baseline scores on the conduct
      problem subscale at the start of the previous DB study were similar for both
      treatment groups: mean values of 33.5 and 33.3 were recorded for placebo- and
      risperidone-treated participants, respectively. At the time of the OL baseline
      visit, mean Conduct Problem Subscale scores were lower in those who had been
      treated with risperidone than in those who remained risperidone-naive (17.5 and
      26.1, respectively). Within 1 week of receiving daily risperidone therapy (mean
      daily dose: 1.38 mg), those participants who had been risperidone-naive at OL
      entry showed a rapid improvement in the Conduct Problem Subscale score. At the
      week 1 assessment, the mean change from baseline for those who had been
      risperidone-naive at OL entry was similar in magnitude to the change from DB
      baseline recorded for participants who had received risperidone in the DB study.
      This mean improvement was sustained in both groups throughout the remainder of
      the OL study. At study endpoint, those participants who had been risperidone
      naive at OL entry experienced a highly significant mean decrease from OL baseline
      in the mean Conduct Problem Subscale score of 10.6 +/- 2.18. The response to
      risperidone in the OL trial remained stable in those participants who had been
      treated with risperidone in the previous DB trial; in this group, the mean change
      at study endpoint from OL baseline was a nonsignificant decrease of 1.26 +/-
      1.45. At DB baseline, 68% of participants had a Clinical Global Impression
      assessment rated as marked, severe, or extremely severe. By DB study endpoint,
      only 17% of participants (15% of whom had received placebo and 19% of whom had
      been treated with risperidone in the previous study) had this severe an
      assessment; 63% of participants had symptoms rated as either none, very mild, or
      mild. Similarly, highly significant decreases from baseline in the Vineland
      Adaptive Behavior Scale rating of the most troublesome symptom (often identified
      as either aggression (hitting, fighting, or temper tantrums) were observed by
      study endpoint after 48 weeks of risperidone therapy. For those participants who
      had received placebo in the previous study, a mean decrease of 47.1 +/- 4.87 mm
      from a DB baseline of 79.4 +/- 2.69 mm was observed. In those who had received
      risperidone, a mean decrease of 43.5 +/- 4.57 mm from a DB baseline of 79.3 +/-
      3.66 mm was observed. Five subgroup analyses of the primary efficacy outcome were
      performed. These included analysis by diagnosis (conduct disorder, oppositional
      defiant disorder, and disruptive behavior disorder-not otherwise specified),
      degree of mental retardation (borderline, mild, moderate), and presence or
      absence of somnolence, attention-deficit/hyperactivity disorder, and
      psychostimulants. The results showed that the efficacy of risperidone was not
      affected by type of disorder, level of retardation, presence/absence of
      somnolence or attention-deficit/hyperactivity disorder, or use of
      psychostimulants. Adverse events were reported for 76 participants; none were
      serious and most were mild/moderate in severity. Somnolence (52%), headache
      (38%), and weight gain (36%) were the most common adverse events. The degree of
      sedation was mild and not associated with cognitive deterioration. In fact, for
      most parameters assessed on the modified California Verbal Learning Test (a test
      for verbal learning and memory), there were statistically significant
      improvements relative to both OL and DB baselines in the mean scores. In
      addition, statistically significant improvements over baseline were also seen for
      some Continuous Performance Task (which is a test for attention and impulsivity)
      parameters. Overall, no deterioration of cognitive function was observed while
      participants were treated with risperidone. Almost half of the 8.5 kg gained was
      attributable to normal growth. Asymptomatic peak prolactin levels were observed
      within 4 weeks of beginning risperidone treatment and declined over time to
      within normal range. At study endpoint, mean prolactin levels were statistically
      significantly greater than baseline only in male participants but still <20
      ng/mL, which is within the normal range. Twenty participants experienced mild or
      moderate extrapyramidal symptoms, although none withdrew for this reason.
      CONCLUSIONS: Risperidone, administered as an oral solution at a mean dose of 1.38
      mg/d (range: 0.02-0.06 mg/kg/d) for 1 year, was well tolerated, safe, and showed
      maintenance of effect in the treatment of disruptive behavior disorders in
      children aged 5 to 12 years with subaverage IQs.

PMID- 12205286
TI  - Factors associated with HIV testing among HIV-positive and HIV-negative high-risk
      adolescents: the REACH Study. Reaching for Excellence in Adolescent Care and
      Health.
AB  - OBJECTIVE: To describe human immunodeficiency virus (HIV) testing patterns among
      high-risk, uninfected adolescents and HIV-infected adolescents, and factors
      associated with testing. METHODS: HIV-infected adolescents (N = 246) and high
      risk, uninfected adolescents (N = 141) at 15 sites nationwide were asked about
      the number of times they were tested for HIV, the type of agency at which testing
      occurred, and reasons for testing. RESULTS: The majority of participants reported
      being influenced to obtain testing by health care providers (53.1% of the HIV
      infected group and 66.1% of the HIV-uninfected group, respectively). Female
      participants were somewhat more likely to have used a confidential or anonymous
      site for the most recent test, compared with male participants (73.5% and 67.5%,
      respectively). Among the HIV-infected group, feeling sick was the only factor
      associated with number of tests. Among the HIV-uninfected group, having more male
      partners, marijuana use in the past 3 months, white race, and having had same
      gender partners in their lifetime (males only) were associated with number of
      tests. Multivariate analyses identified 2 significant models. Modeling the
      probability of having been tested 3 or more times, black participants were less
      likely to be tested than white participants (odds ratio [OR] = 0.4), and
      participants who felt sick were more likely to be tested than those who did not
      (OR = 1.7). Modeling the probability that the last test would be positive, black
      participants were more likely than white participants to test positive (OR =
      2.3); those who were tested because they thought they might have gotten HIV from
      sex (OR = 3.0) or they felt sick (OR = 3.9) were more likely to test positive;
      participants who were tested because a health care professional recommended it
      were actually less likely (OR = 0.5) to test positive. CONCLUSIONS: Overall,
      these findings highlight the importance of making HIV testing more routinely
      available to sexually active adolescents. More work needs to be done to normalize
      HIV testing among adolescents, and more innovative approaches need to be
      implemented on a wide scale.

PMID- 12205287
TI  - Outcomes of primary image-guided drainage of parapneumonic effusions in children.
AB  - OBJECTIVE: To assess the outcome of image-guided needle aspiration when compared
      with image-guided percutaneous catheter drainage in the management of
      parapneumonic effusions in children. METHODS: A retrospective chart review was
      conducted of the medical records, microbiology, and radiology reports of 67
      children who presented with parapneumonic effusions and underwent primary image
      guided drainage between April 1, 1995, and April 1, 2000. RESULTS: Thirty-four
      patients had aspiration only, and 33 patients had pigtail catheters placed. The 2
      drainage methods had similar median length of stay and complication rates. The
      reintervention rate in this study was 27% (18 patients). Children who underwent
      primary aspiration without catheter placement had significantly higher rates of
      reintervention. Method of drainage, pH lower than 7.2, and loculation of the
      fluid collection were independent predictors of reintervention. A low glucose
      level was an additive predictor of reintervention when the pH was low.
      CONCLUSIONS: Aspiration and catheter drainage of parapneumonic effusions had
      similar complication rates and lengths of stay, but children who underwent
      primary aspiration had significantly higher reintervention rates, particularly
      when pH and glucose levels were low. Therefore, primary catheter placement for
      parapneumonic effusions should be considered in children who undergo diagnostic
      thoracentesis. The decision regarding tube placement could be facilitated by the
      on-site availability of a pH meter and a glucometer.

PMID- 12205285
TI  - Maternal adherence to the zidovudine regimen for HIV-exposed infants to prevent
      HIV infection: a preliminary study.
AB  - OBJECTIVE: To describe the extent of adherence to the recommended neonatal
      zidovudine (ZDV) regimen administered to infants who have been exposed to the
      human immunodeficiency virus (HIV) to prevent mother-to-child transmission of HIV
      and to determine which maternal factors are associated with compliance. METHODS:
      HIV-infected women (n = 87) who were participating in a larger study of perinatal
      transmission at 3 inner-city New York City hospitals were interviewed 2 to 6
      weeks' postpartum to assess adherence to neonatal prophylaxis, social support,
      social network factors, and depression. In addition, plasma samples of 45 of
      their infants were assayed for ZDV levels. RESULTS: A majority of women (71%)
      administered all of the prescribed 4 daily doses in the previous week, as
      measured by interview; self-reported adherence was not associated with any
      maternal characteristics. In contrast, poor adherence, as measured by lower
      infant ZDV plasma levels, was associated with asymptomatic HIV illness in the
      mother and having 2 or more other children; good adherence, as indicated by
      higher ZDV levels, was associated with the presence of a maternal social support
      network, disclosure of HIV infection, and mothers' adherence to their own ZDV
      regimens during pregnancy. In multivariate regression analyses, maternal
      asymptomatic status (beta = -0.40) was associated with lower infant ZDV levels,
      and maternal adherence during pregnancy (beta = 0.37) was associated with higher
      levels. CONCLUSIONS: Women who are HIV asymptomatic and lack a social support
      network are more likely not to comply with the recommended neonatal prophylactic
      regimen of antiretroviral therapy. Future studies should address the prenatal
      period and social network factors, such as disclosure of serostatus, and the
      custody of other children.

PMID- 12205288
TI  - Nebulized morphine as a treatment for dyspnea in a child with cystic fibrosis.
AB  - OBJECTIVE: To shed light on nebulized morphine, a new treatment for dyspnea in
      children with terminal lung disease. METHODS: A clinical case study was conducted
      on a patient in a tertiary care medical center. RESULTS: Nebulized morphine was
      administered in incremental doses ranging from 2.5 mg to 12.5 mg in a 10-year
      old, 20-kg boy with end-stage cystic fibrosis. Before the nebulized morphine
      treatments were started, a dose of nebulized lidocaine failed to provide the
      patient with any relief. After each dose of morphine, the following parameters
      were recorded: visual analog "dyspnea" scores, vital signs, venous blood gases,
      and blood levels of morphine. The nebulized morphine was found to have a modest
      effect on the patient's dyspnea, with no significant differences found between
      the varying doses. Venous carbon dioxide tension levels increased <4 mm Hg for
      all doses except 12.5 mg, for which there was a 9-mm Hg increase. Systemic blood
      levels of morphine were <10 ng/mL at all doses. The nebulized morphine did not
      cause any significant changes in blood pressure or heart rate for doses <12.5 mg.
      CONCLUSIONS: Inhaled morphine was associated with a mild, beneficial effect on
      dyspnea, with minimal differences found between the lowest and highest doses.
      This "ceiling" effect may be the result of saturation of opioid receptors in the
      lung, the variable bioavailability of inhaled morphine, or a placebo response.
      More studies are needed to determine what, if any, the optimum dose of nebulized
      morphine is for children.

PMID- 12205289
TI  - Kimura's disease: a diagnostic challenge.
AB  - Kimura's disease is a rare inflammatory disorder of unknown cause, primarily seen
      in young Asian males. The disease is characterized by a triad of painless
      subcutaneous masses in the head or neck region, blood and tissue eosinophilia,
      and markedly elevated serum immunoglobulin E levels. We describe an 11-year-old
      Asian boy with Kimura's disease who presented with a chronic left neck mass. The
      diagnosis was based on the characteristic histopathologic findings after surgical
      excision in conjunction with peripheral eosinophilia and elevated serum
      immunoglobulin E levels. Pediatricians in western countries should be aware of
      the clinical presentation of Kimura's disease.

PMID- 12205290
TI  - Heterozygous alpha 2A-adrenergic receptor mice unveil unique therapeutic benefits
      of partial agonists.
AB  - Genetic manipulation of the alpha(2A)-adrenergic receptor (alpha(2A)-AR) in mice
      has revealed the role of this subtype in numerous responses, including agonist
      induced hypotension and sedation. Unexpectedly, alpha(2)-agonist treatment of
      mice heterozygous for the alpha(2A)-AR (alpha(2A)-AR(+/-)) lowers blood pressure
      without sedation, indicating that more than 50% of alpha(2A)-AR must be activated
      to evoke sedation. We postulated that partial activation of alpha(2A)-AR in wild
      type alpha(2A)-AR(+/+) animals could be achieved with partial agonists, agents
      with variable ability to couple receptor occupancy to effector activation, and
      might elicit one versus another pharmacological response. In vitro assays reveal
      that moxonidine is a partial agonist at alpha(2A)-AR. Although moxonidine was
      developed to preferentially interact with imidazoline binding sites, it requires
      the alpha(2A)-AR to lower blood pressure because we observe no hypotensive
      response to moxonidine in alpha(2A)-AR-null (alpha(2A)-AR(-/-)) mice. Moreover,
      we observe that moxonidine lowers blood pressure without sedation in wild-type
      mice, consistent with the above hypothesis regarding partial agonists. Our
      findings suggest that weak partial agonists can evoke response-selective pathways
      and might be exploited successfully to achieve alpha(2A)-AR pharmacotherapy where
      concomitant sedation is undesirable, i.e., in treatment of depression or
      attention deficit hyperactivity disorder, in suppression of epileptogenesis, or
      enhancement of cognition. Furthermore, rigorous physiological and behavioral
      assessment of mice heterozygous for particular receptors provides a general
      strategy for elucidation of pathways that might be selectively activated by
      partial agonists, thus achieving response-specific therapy.

PMID- 12205291
TI  - Whole-genome comparative analysis of three phytopathogenic Xylella fastidiosa
      strains.
AB  - Xylella fastidiosa (Xf) causes wilt disease in plants and is responsible for
      major economic and crop losses globally. Owing to the public importance of this
      phytopathogen we embarked on a comparative analysis of the complete genome of Xf
      pv citrus and the partial genomes of two recently sequenced strains of this
      species: Xf pv almond and Xf pv oleander, which cause leaf scorch in almond and
      oleander plants, respectively. We report a reanalysis of the previously sequenced
      Xf 9a5c (CVC, citrus) strain and the two "gapped" Xf genomes revealing ORFs
      encoding critical functions in pathogenicity and conjugative transfer. Second, a
      detailed whole-genome functional comparison was based on the three sequenced Xf
      strains, identifying the unique genes present in each strain, in addition to
      those shared between strains. Third, an "in silico" cellular reconstruction of
      these organisms was made, based on a comparison of their core functional
      subsystems that led to a characterization of their conjugative transfer
      machinery, identification of potential differences in their adhesion mechanisms,
      and highlighting of the absence of a classical quorum-sensing mechanism. This
      study demonstrates the effectiveness of comparative analysis strategies in the
      interpretation of genomes that are closely related.

PMID- 12205292
TI  - M-FISH analysis shows that complex chromosome aberrations induced by alpha 
      particle tracks are cumulative products of localized rearrangements.
AB  - Complex chromosome aberrations are characteristically induced after exposure to
      low doses of densely ionizing radiation, but little is understood about their
      formation. To address this issue, we irradiated human peripheral blood
      lymphocytes in vitro with 0.5 Gy densely ionizing alpha-particles (mean of 1
      alpha-particle/cell) and analyzed the chromosome aberrations produced by using 24
      color multiplex fluorescence in situ hybridization (M-FISH). Our data suggest
      that complex formation is a consequence of direct nuclear alpha-particle
      traversal and show that the likely product of illegitimate repair of damage from
      a single alpha-particle is a single complex exchange. From an assessment of the
      "cycle structure" of each complex exchange we predict alpha-particle-induced
      damage to be repaired at specific localized sites, and complexes to be formed as
      cumulative products of this repair.

PMID- 12205293
TI  - Topical applications of caffeine or (-)-epigallocatechin gallate (EGCG) inhibit
      carcinogenesis and selectively increase apoptosis in UVB-induced skin tumors in
      mice.
AB  - SKH-1 hairless mice were irradiated with ultraviolet B (UVB) twice weekly for 20
      weeks. These tumor-free mice, which had a high risk of developing skin tumors
      during the next several months, were then treated topically with caffeine (6.2
      micromol) or (-)-epigallocatechin gallate (EGCG; 6.5 micromol) once a day 5 days
      a week for 18 weeks in the absence of further treatment with UVB. Topical
      applications of caffeine to these mice decreased the number of nonmalignant and
      malignant skin tumors per mouse by 44% and 72%, respectively. Topical
      applications of EGCG decreased the number of nonmalignant and malignant tumors
      per mouse by 55% and 66%, respectively. Immunohistochemical analysis showed that
      topical applications of caffeine or EGCG increased apoptosis as measured by the
      number of caspase 3-positive cells in nonmalignant skin tumors by 87% or 72%,
      respectively, and in squamous cell carcinomas by 92% or 56%, respectively, but
      there was no effect on apoptosis in nontumor areas of the epidermis. Topical
      applications of caffeine or EGCG had a small inhibitory effect on proliferation
      in nonmalignant tumors as measured by BrdUrd labeling (16-22%), and there was
      also a similar, but nonsignificant, inhibitory effect on proliferation in
      malignant tumors. The results suggest a need for further studies to determine
      whether topical applications of caffeine or EGCG can inhibit sunlight-induced
      skin cancer in humans.

PMID- 12205294
TI  - Genomic profiles of clinical and environmental isolates of Vibrio cholerae O1 in
      cholera-endemic areas of Bangladesh.
AB  - Diversity, relatedness, and ecological interactions of toxigenic Vibrio cholerae
      O1 populations in two distinctive habitats, the human intestine and the aquatic
      environment, were analyzed. Twenty environmental isolates and 42 clinical
      isolates were selected for study by matching serotype, geographic location of
      isolation in Bangladesh, and season of isolation. Genetic profiling was done by
      enterobacterial repetitive intergenic consensus sequence-PCR, optimized for
      profiling by using the fully sequenced V. cholerae El Tor N16961 genome. Five
      significant clonal clusters of haplotypes were found from 57 electrophoretic
      types. Isolates from different areas or habitats intermingled in two of the five
      significant clusters. Frequencies of haplotypes differed significantly only
      between the environmental populations (exact test; P < 0.05). Analysis of
      molecular variance yielded a population genetic structure reflecting the
      differentiating effects of geographic area, habitat, and sampling time. Although
      a parameter confounding the latter differences explained 9% of the total
      molecular variance in the entire population (P < 0.01), the net effect of habitat
      and time could not be separated because of the small number of environmental
      isolates included in the study. Five subpopulations from a single area were
      determined, and from these we were able to estimate a relative differentiating
      effect of habitat, which was small compared with the effect of temporal change.
      In conclusion, the resulting population structure supports the hypothesis that
      spatial and temporal fluctuations in the composition of toxigenic V. cholerae
      populations in the aquatic environment can cause shifts in the dynamics of the
      disease.

PMID- 12205296
TI  - Evidence-based medicine: sounds good. What is it?

PMID- 12205297
TI  - Nontuberculous mycobacteria.

PMID- 12205295
TI  - Nerve growth factor and galantamine ameliorate early signs of neurodegeneration
      in anti-nerve growth factor mice.
AB  - Phenotypic knockout of nerve growth factor (NGF) activity in transgenic anti-NGF
      mice (AD11 mice) results in a progressive neurodegenerative phenotype resembling
      Alzheimer's disease. In this article, we examine whether and how the progressive
      neurodegenerative phenotype of AD11 mice could be prevented or ameliorated by
      pharmacological treatments with NGF or the cholinergic agonist galantamine, at a
      relatively early phase of Alzheimer's disease-like neurodegeneration. We
      demonstrate that the neurodegeneration induced by the expression of anti-NGF
      antibodies in AD11 mice can be largely reversed by NGF delivery through an
      olfactory route.

PMID- 12205298
TI  - Performance-enhancing: substances and their use among adolescent athletes.

PMID- 12205299
TI  - Evidence-based medicine for the pediatrician.

PMID- 12205300
TI  - Index of suspicion.

PMID- 12205301
TI  - Question from the clinician: phages in infections.

PMID- 12205302
TI  - Aspiration in infants and children.

PMID- 12205332
TI  - Faecal calprotectin: a bright future for assessing disease activity in Crohn's
      disease.

PMID- 12205333
TI  - The relationship between the thyroid gland and the liver.
AB  - Thyroxine and tri-iodothyronine are essential for normal organ growth,
      development and function. These hormones regulate the basal metabolic rate of all
      cells, including hepatocytes, and thereby modulate hepatic function; the liver in
      turn metabolizes the thyroid hormones and regulates their systemic endocrine
      effects. Thyroid dysfunction may perturb liver function, liver disease modulates
      thyroid hormone metabolism, and a variety of systemic diseases affect both
      organs. We highlight the intricate relations between the thyroid gland and the
      liver in health and disease.

PMID- 12205334
TI  - Selective recording in blood pressure readings may increase subsequent mortality.
AB  - BACKGROUND: Rounding blood pressure (BP) to the nearest 10 mmHg (terminal digit
      preference) and selecting for particular values near treatment cut-offs (number
      preference) have both been previously described. Both reduce measurement
      accuracy, and may have consequences for treatment and survival. AIM: To check for
      number preference in screening for hypertension, and whether this influenced
      subsequent mortality. DESIGN: Prospective case-control screening study. METHODS:
      In the General Practice Hypertensive Study Group (GPHSG), prospective case
      control study patients (n=23 574) were screened on one occasion for high phase-IV
      diastolic BP (DBP4) (> or =90 mmHg). Identified cases were matched with
      normotensive controls for age, sex, date of screen and ethnic group, and were
      registered for mortality follow-up (n=6310). Patients with a high DBP4 had two
      further readings, and were treated if it remained elevated. RESULTS: For DBP4
      terminal digit, '0' was over-represented (28.2% vs. 20%), and the number '88' was
      over-represented in both men and women. There was an excess adjusted death rate
      for females with DBP4 88-89 mmHg vs. 90-99 mmHg for both cardiovascular (RR 2.56,
      95%CI 1.43-4.56, p=0.0015) and all-cause (1.56, 95%CI 1.06-2.29, p=0.023)
      mortality. For males, the corresponding rates were non-significantly reduced:
      cardiovascular RR 0.69, 95%CI 0.42-1.14, p=0.15; all-cause RR 0.93, 95%CI 0.68
      1.27, p=0.64. DISCUSSION: The quality of BP measurements should be monitored both
      in research studies and in clinical practice as part of clinical governance
      procedures.

PMID- 12205335
TI  - Acute renal failure requiring renal replacement therapy: incidence and outcome.
AB  - BACKGROUND: Renal replacement therapy (RRT) for acute renal failure (ARF) may be
      provided in many settings within the hospital. Such patients require a high level
      of care and often have a poor prognosis. No prospective studies have accurately
      defined this population, making the prediction of necessary resources and the
      planning of services difficult. AIM: To ascertain the incidence, causes and
      outcomes of acute renal failure requiring renal replacement therapy in Scotland.
      DESIGN: A prospective observational census of all clinical areas providing renal
      replacement therapy in three Scottish health boards (Grampian, Highland,
      Tayside). METHODS: Patients were identified by liaison with each unit providing
      RRT. Factors precipitating renal failure and reasons for RRT were recorded at the
      time of initiation. Comorbid disease burden was scored using the Charlson index.
      Patient status at 90 days was assessed from case-notes, contacting general
      practitioners where necessary. RESULTS: 375 patients per million population per
      year received RRT; 203 per million per year for either ARF or acute-on-chronic
      renal failure. 73.5% of patients receiving RRT for ARF died within 90 days, 23.5%
      became independent of RRT. The median duration of hospital admission was 19 days.
      DISCUSSION: The annual incidence of ARF requiring RRT is just over 200 per
      million population, almost twice that of end-stage renal disease requiring RRT.
      Such treatment places high demands upon health care resources.

PMID- 12205336
TI  - High incidence of renal failure requiring short-term dialysis: a prospective
      observational study.
AB  - BACKGROUND: Previous estimates of incidence of acute renal failure (ARF)
      requiring renal replacement therapy have varied from 18 to 75 patients per
      million per year, but have been beset by problems of definition. AIM: To
      investigate whether the '90-day rule' provides a more reliable, reproducible and
      robust estimate of the need for short-term dialysis. SETTING: District general
      hospital serving a population of 147 000. DESIGN: Prospective observational
      study. METHODS: Patients who received renal replacement therapy in Dumfries and
      Galloway between 01/01/94 and 31/12/2000 were divided into two groups: long-term
      dialysis (> or =90 days) and short-term dialysis (<90 days). RESULTS: Of 302
      patients, 193 received short-term dialysis, giving an incidence for short-term
      dialysis of 187 patient episodes per million per year (95%CI 170-203). Use of a
      more conventional definition for ARF (including all ARF and acute-on-chronic
      renal failure, but excluding patients with chronic renal failure who present
      acutely) produced a similar estimate at 176 patients per million per year (95%CI
      160-193). DISCUSSION: The 90-day rule estimated the incidence of short-term
      dialysis/ARF at nearly twice the incidence of chronic renal failure requiring
      dialysis, and more than twice the most recent estimate of the incidence of ARF in
      the UK. The main attraction of the 90-day rule is its simplicity. If the high
      level of short-term dialysis/ARF found in our study is confirmed by other
      centres, there are significant resource implications for the provision of renal
      care.

PMID- 12205337
TI  - Hazardous and harmful drinking: a comparison of the AUDIT and CAGE screening
      questionnaires.
AB  - BACKGROUND: Hazardous and harmful use of alcohol remains a public health concern,
      and many general hospital admissions are alcohol-related. AIM: To compare the
      CAGE and Alcohol Use Disorders Identification Test (AUDIT) questionnaires in
      screening general medical admissions for harmful or hazardous drinking. DESIGN:
      Prospective questionnaire-based study. METHODS: Both questionnaires were
      administered, and demographic data collected. RESULTS: One hundred and three
      patients were included. Of these, 36% were identified by the AUDIT to be drinking
      hazardously or harmfully, and 22% were identified as CAGE cases. All CAGE cases
      were also AUDIT cases. DISCUSSION: As the CAGE and the AUDIT are designed to
      identify different populations, it is not surprising that significantly fewer
      cases were identified using the CAGE. The AUDIT identifies not just the harmful
      drinkers detected by the CAGE, but also hazardous drinkers, who have not yet
      reached that level of harm. As drinkers at an earlier stage may respond better to
      interventions aimed at reducing their consumption, the AUDIT is preferable in
      clinical practice.

PMID- 12205338
TI  - Early treatment with allopurinol in familial juvenile hyerpuricaemic nephropathy
      (FJHN) ameliorates the long-term progression of renal disease.
AB  - BACKGROUND: The efficacy of allopurinol in autosomal dominant familial juvenile
      hyperuricaemic nephropathy (FJHN) has been disputed. AIM: To address this
      question, in the absence of controlled trials. DESIGN: Retrospective long-term
      follow-up study. METHODS: All kindreds were biochemically screened. Measurements
      included uric acid clearance, creatinine clearance, serum creatinine, and
      glomerular filtration rate (GFR). We used five siblings who had died or
      progressed to transplantation, ten other deceased relatives, and two index cases
      (one untreated, one non-compliant) as controls to assess the effects of
      allopurinol. RESULTS: Of eight families with FJHN, six had a strong history of
      renal disease and early parental death (mean age 41 years, n=10). Of 27 patients
      started immediately on allopurinol and treated uninterruptedly, 21 responded
      well, including three children born subsequently. Eight siblings (mean age 19
      years) with a normal plasma creatinine at start (<120 micromol/l, mean GFR 80
      ml/min/1.73 m(2)) retained stable renal function (mean 14.5 years, mean age 34
      years, GFR 85 ml/min/1.73 m(2)). Of the 13 other responders, treated for up to 34
      years, 10 with a creatinine <200 micromol/l at diagnosis (mean age 28 years, mean
      creatinine 137 micromol/l at start) now have a mean creatinine of 210 micromol/l.
      In contrast, five patients (mean age 26 years) with a creatinine >200 micromol/l
      (GFR <35 ml/min/1.73 m(2)) when allopurinol commenced, plus one untreated index
      case, all progressed rapidly (mean 6 years) to end-stage renal failure. In two
      others (one non-compliant, one initially untreated), GFR fell by >50% in 7 years.
      Introduction of allopurinol in the latter has stabilized GFR. DISCUSSION:
      Allopurinol reduced the morbidity and mortality from renal failure seen in
      untreated siblings and previous generations of these families. Early diagnosis of
      FJHN is important, so that treatment can begin before irreversible renal damage
      has developed.

PMID- 12205339
TI  - Paracetamol toxicity: epidemiology, prevention and costs to the health-care
      system.
AB  - Paracetamol has been used as an analgesic and antipyretic for many years, with
      toxicity first noted in the 1960s. Since then the incidence of poisoning has
      increased, and paracetamol is now the most common drug in self-poisoning, with a
      high rate of morbidity and mortality. The use, abuse and ways of reducing
      paracetamol toxicity are reviewed, but in view of the potential for harm, serious
      consideration should be given to changing the legal status of paracetamol,
      possibly to a prescription-only medicine.

PMID- 12205341
TI  - Abciximab-induced thrombocytopenia.

PMID- 12205342
TI  - A recurrent rash treated by oophorectomy.

PMID- 12205343
TI  - Diagnosing deep-vein thrombosis.

PMID- 12205344
TI  - Functional foods.

PMID- 12205346
TI  - Sidebranch occlusion after coronary stenting with or without balloon predilation:
      direct versus conventional stenting.
AB  - Direct stenting (DS) is a novel approach in percutaneous treatment of coronary
      artery lesions. Several studies confirmed the safety and feasibility of the
      procedure with success rates greater than 90%. However, the data regarding the
      incidence of sidebranch occlusion (SBO) after DS are scarce. The purpose of this
      study was to evaluate SBO (> 1 mm) after DS and compare it to conventional
      stenting (CS) with balloon predilation. The study population consisted of 151
      patients (88 underwent DS, 63 underwent CS) with 185 sidebranches jailed by the
      stent (110 in DS group, 75 in CS group). SBO was observed in 20 out of 110
      patients in the DS group (18.2%) and 18 out of 75 patients in the CS group (24%).
      Although the incidence of SBO was higher in the CS group compared to the DS group
      (24% vs. 18.2%, respectively), these values did not reach statistical
      significance (p > 0.05). Most of the SBOs were observed in cases with type D
      sidebranch morphology (p < 0.001) and in cases with sidebranch ostial diameter
      stenosis   50% (p = 0.019). None of the other clinical and angiographic variables
      predicted the SBO. To the best of our knowledge, this is the first report
      comparing incidence of SBO between two different PCI methods (CS vs DS).
      Randomized studies with larger patient populations should be conducted to compare
      this approach with conventional stenting.

PMID- 12205347
TI  - Sidebranch patency during main branch stenting: try to keep the branch open
      immediate and long-term!

PMID- 12205348
TI  - Optimization of local methylprednisolone delivery to inhibit inflammatory
      reaction and neointimal hyperplasia of coated coronary stents.
AB  - Polymer coating can optimize the surface characteristics of metallic coronary
      stents and serve as a vehicle for local drug delivery. Major problems, however,
      include the lack of biocompatibility of the polymers used and the limited amount
      of drug that can be loaded onto the stent. Stainless-steel stents were spray
      coated or spray-coated combined with a barrier coating using a fluorinated
      polymethacrylate PFM-P75 impregnated with different methylprednisolone
      concentrations. When spray-coated with highly concentrated methylprednisolone (
      33%) fluorinated polymethacrylate PFM-P75, the surface became progressively more
      rough. Adding a barrier coating, however, could decrease these surface
      irregularities of methylprednisolone-loaded PFM-P75 spray-coated stents. In
      vitro, most of the methylprednisolone was released in the first 48 hours. A
      barrier coating could dramatically slow down the drug release from 80% to 13%
      during the first 48 hours. Histomorphometric analysis showed that the
      inflammatory response and neointimal hyperplasia of methylprednisolone-loaded
      stents were lower than in control stents. Neointimal hyperplasia of
      methylprednisolone-loaded PFM-P75 stents spray-coated with a barrier coating was
      decreased compared to the non-barrier-coated methylprednisolone-loaded stents. In
      conclusion, spray coating enables the use of high methylprednisolone
      concentrations. A barrier coating could significantly slow down the
      methylprednisolone release. Methylprednisolone-loaded PFM-P75-coated stents could
      significantly inhibit the inflammatory response and neointimal hyperplasia. The
      response to methylprednisolone was related to the dose used and the release time
      of the drug.

PMID- 12205349
TI  - Is zero enough?

PMID- 12205350
TI  - Reduction of early elastic recoil by cutting balloon angioplasty as compared to
      conventional balloon angioplasty.
AB  - BACKGROUND: Restenosis after successful balloon angioplasty remains problematic.
      Early elastic response after angioplasty is significant when considering the
      possible development of restenosis. The purpose of this study was to compare
      early elastic recoil within 10 minutes after successful percutaneous transluminal
      coronary angioplasty and early lumen loss at 24 hours after angioplasty in a
      cutting balloon group and a conventional balloon group. METHODS: Extent of early
      elastic recoil was quantitatively measured as the difference of mean balloon
      diameter at maximal inflation pressure and minimal luminal diameter after
      angioplasty in 82 cutting balloon-treated lesions and 51 conventional balloon
      treated lesions. RESULTS: Reference diameter and balloon/artery ratio were
      similar between the cutting balloon and conventional balloon groups (2.89   0.47
      mm vs. 2.88   0.60 mm; 1.19   0.11 vs. 1.19   0.13, respectively). Early elastic
      recoil after angioplasty was significantly smaller in the cutting balloon than
      the conventional balloon group (0.96   0.40 mm vs. 1.12   0.37 mm, respectively;
      p = 0.04). Also, the mean amount of lumen loss from 10 minutes after angioplasty
      to 24 hours after was significantly smaller in the cutting balloon than the
      conventional balloon group (0.08   0.28 mm vs. 0.20   0.33 mm, respectively; p =
      0.02). CONCLUSION: There is significantly less early elastic recoil in the
      cutting balloon angioplasty than in the conventional balloon angioplasty group.
      The efficacy of cutting balloon continues 24 hours after angioplasty.

PMID- 12205351
TI  - Cutting balloon angioplasty   teaching the old dog new tricks!

PMID- 12205353
TI  - Anterior ischemia secondary to embolization of the posterior descending artery in
      a patient with a chronic total occlusion of the left anterior descending artery.

PMID- 12205352
TI  - Outcome of percutaneous mitral balloon valvuloplasty: comparison of the inoue and
      retrograde non-transseptal techniques. A single-center experience.
AB  - INTRODUCTION: The transseptal Inoue (IN) and to a lesser extend retrograde non
      transseptal (RNT) techniques are established procedures for percutaneous mitral
      balloon valvuloplasty (PBMV) in patients with mitral stenosis. However, a head to
      head comparison of these two techniques, especially from a single center, has not
      yet been reported. METHODS: Seventy-two consecutive patients (n = 35 IN and n =
      37 RNT) underwent PMBV in our clinic from October 1993 to December 1999. All
      baseline and procedural characteristics were compared, as well as immediate and
      long-term outcomes (mean follow-up, 42   12 months) of the patients. RESULTS:
      Baseline characteristics were similar in the two groups. A successful immediate
      result was achieved in 91% of IN patients and 89% of RNT patients. After the
      PMBV, mitral valve area (MVA) increased from 1.04   0.16 cm2 to 1.6   0.3 cm2 and
      from 1.06   0.23 cm2 to 1.55   0.3 cm2 in the IN group and RNT group,
      respectively (p = NS). There was a higher percentage of mild mitral regurgitation
      (MR) after the RNT technique (p = 0.03). Mean fluoroscopy time was 31   16
      minutes in the IN group and 39   11 minutes in the RNT group (p = 0.02). After
      discharge, major adverse cardiac events (MACE: mitral valve replacement, repeat
      PMBV) occurred in 3 patients (8%) patients in the IN group and 5 patients (13.5%)
      in the RNT group (p = NS). Follow-up echocardiographic evaluation revealed no
      significant changes regarding MVA in either group. CONCLUSIONS: The IN and RNT
      techniques are comparable regarding the achieved MVA, with slightly more frequent
      MR post-RNT PBMV. IN requires significantly less fluoroscopy time. MACE and event
      free survival rates at follow-up were similar in the two groups.

PMID- 12205354
TI  - Closure of a very large patent ductus arteriosus using the amplatzer duct
      occluder.
AB  - A very large patent ductus arteriosus was closed completely using an Amplatzer
      Duct Occluder. This represents the largest patent ductus arteriosus to undergo
      closure with this endovascular technique.

PMID- 12205355
TI  - A blind comparison of four non-invasive twelve-lead electrocardiogram algorithms
      for predicting susceptibility to ventricular tachycardia.
AB  - INTRODUCTION: To reduce QT measurement error, a new method was tested in which
      high-gain, high-speed, simultaneous 12-lead electrocardiographic (ECG) recordings
      were obtained during a single cardiac cycle. To increase its predictive power,
      the utility of combining QTD with the QRS duration for predicting susceptibility
      to ventricular tachyarrhythmia (VT) was analyzed. METHODS AND RESULTS: A total of
      113 patients referred for electrophysiological study underwent baseline
      simultaneous 12-lead ECG followed by electrophysiological study to determine VT
      inducibility. Twenty-six patients had inducible VT while 87 patients did not. QT
      intervals and the width of QRS complex were measured from a single cardiac cycle
      with high-gain (8 times normal) and high-speed (100 mm/second) 12-lead ECG
      recordings. This method resulted in 100% QT interval identification throughout
      all 12 leads for every patient. Receiver-operator characteristic curves (ROC) and
      the areas under the ROC curves (AUC) were used to quantitatively analyze the
      performance of four ECG variables (QTD3, QTD12, QTD12 + QRS and QTD3 + QRS). All
      four ECG variables were significantly increased in the patients with inducible VT
      as compared to those without inducible VT. The QTD3 algorithm was less useful
      than QTD12 in predicting inducible VT; however, the addition of QRS duration to
      all QTD algorithms enhanced VT detection. CONCLUSION: 1) QRS duration has an
      incremental benefit in the detection of VT when combined with QTD; 2) QTD12 + QRS
      duration provided the highest predictive power among the four tested algorithms;
      3) high-gain, high-speed 12-lead ECG recordings reduced QT measurement error.

PMID- 12205356
TI  - Embolization containment device for a native coronary arterial lesion with large
      thrombus burden.
AB  - Distal embolization and no reflow, resulting in myocardial infarction, are
      frequently observed during percutaneous coronary intervention in lesions with
      large thrombus burden. This case report describes the successful treatment of a
      lesion with large thrombus burden with an embolization containment device.

PMID- 12205357
TI  - Cutting and stenting in a heavily calcified left anterior descending artery
      lesion.
AB  - The significance of heavily calcified proximal left anterior descending coronary
      artery stenosis in a 57-year-old man was assessed physiologically using a Doppler
      flow wire. Intravascular ultrasound guidance allowed for adequate dilatation with
      a cutting balloon and optimization of stent deployment. The cutting balloon
      offers an effective alternative in this challenging scenario.

PMID- 12205359
TI  - Cutting balloon angioplasty through stent struts of a  jailed  sidebranch ostial
      lesion.
AB  - The treatment of sidebranch ostial lesions  jailed  after stent implantation is
      challenging. We report a case of successful Cutting Balloon angioplasty through
      stent struts of a severe, elastic sidebranch ostial lesion. Three-day follow-up
      angiography showed no recurrent stenosis. The patient was discharged with
      complete resolution of chest discomfort and the post-hospitalization course was
      uneventful. Cutting Balloon angioplasty may be an optimal strategy for the
      treatment of elastic ostial lesions in smaller vessels that are suboptimal for
      stenting. The long-term benefits of using a Cutting Balloon for the treatment of
      sidebranch ostial lesions are still to be determined.

PMID- 12205358
TI  - Cutting balloon angioplasty.
AB  - The Cutting Balloon is a unique angioplasty device used in percutaneous coronary
      interventions. The advantage of the Cutting Balloon is its ability to reduce
      vessel stretch and vessel injury by scoring the vessel longitudinally rather than
      causing an uncontrolled disruption of the atherosclerotic plaque. The atherotomes
      deliver a controlled fault line during dilatation to ensure that the crack
      propagation ensues in an orderly fashion. Lower balloon inflation pressures (4 8
      atmospheres) are recommended with the Cutting Balloon. The Cutting Balloon also
      dilates the target vessel with less force to decrease the risk of a
      neoproliferative response and in-stent restenosis.

PMID- 12205360
TI  - Successful treatment with primary angioplasty of acute myocardial infarction
      during cerebellar hemorrhage.
AB  - We describe a case of acute myocardial infarction related to a cerebellar
      hemorrhage. The infarction occurred just before the neurosurgical operation of
      ventricular drainage and was successfully treated by primary coronary
      angioplasty, with the implantation of coated stents and low doses of glycoprotein
      (GP) IIb/IIIa inhibitors. The patient recovered well from both interventions and
      the 6-month follow-up angiography showed a good result.

PMID- 12205361
TI  - Integrating GP IIb/IIIa inhibition into treatment strategies for acute ST
      elevation myocardial infarction.

PMID- 12205362
TI  - KVTeO5 and a redetermination of the Na homologue.
AB  - A single crystal of KVTeO(5), potassium vanadium tellurite, has been grown. The
      present structure determination has been conducted together with the refinement
      of the NaVTeO(5) homologue, sodium vanadium tellurite, for the sake of precise
      comparison. The network consists of [VTeO(5)](n) ribbons built up by VO(4)
      tetrahedra linking centrosymmetric Te(2)O(6) groups and stacked along the [010]
      direction; the alkali cations are intercalated in between. The Te(IV) atom
      exhibits a typical one-sided coordination number (CN) of 4, completed by a lone
      pair, which forms a distorted triangular bipyramid with the four O atoms.

PMID- 12205363
TI  - Bis(trichlorophosphine)iminium salts, [Cl3P=N=PCl3]+, with transition metal
      halide counter-ions.
AB  - The structures of four bis(trichlorophosphine)iminium [[Cl(3)P=N=PCl(3)](+);
      systematic name: trichloro[(trichlorophosphoranylidene)iminio]phosphorus(V)]
      salts, namely bis(trichlorophosphine)iminium hexachloroniobate,
      (Cl(6)NP(2))[NbCl(6)], (I), bis(trichlorophosphine)iminium hexachlorotantalate,
      (Cl(6)NP(2))[TaCl(6)], (II), bis(trichlorophosphine)iminium tri-micro-chloro
      bis[trichlorotitanium(IV)], (Cl(6)NP(2))[Ti(2)Cl(9)], (III), and
      bis[bis(trichlorophosphine)iminium] di-micro-chloro
      bis[tetrachlorozirconium(IV)], (Cl(6)NP(2))(2)[Zr(2)Cl(10)], (IV), have been
      determined. The P=N distances in the discrete [Cl(3)P=N=PCl(3)](+) moieties in
      structures (I), (II) and (IV) range from 1.5460 (14) to 1.5554 (16) A, and the
      P=N=P angles range from 136.8 (3) to 143.4 (4) degrees. The [Cl(3)P=N=PCl(3)](+)
      cation in (III) is disordered and the calculated geometries for the cation are
      therefore less reliable. Compounds (I) and (II) are isostructural and the metal
      anions have slightly distorted octahedral geometries. The anion in compound (III)
      consists of two distorted octahedral Ti centres linked by three micro (2)-Cl
      atoms, while in compound (IV), the dianion is derived from two distorted edge
      shared ZrCl(6) octahedra.

PMID- 12205364
TI  - Cs[Ag4Zn2(SCN)9].
AB  - Caesium tetrasilver dizinc nonathiocyanate, Cs[Ag(4)Zn(2)(SCN)(9)], forms a
      continuous structure, where the Ag atoms and the S atoms of the thiocyanate
      groups form chains which run along [101]. These chains are bonded together
      through the Cs and Zn atoms. It is not possible to distinguish between space
      groups P1 and P-1, but, if the latter space group is correct, the structure
      contains a thiocyanate group disordered across a centre of inversion. The
      structure is described in space group P-1, in which the Cs atom also lies on a
      centre of inversion.

PMID- 12205365
TI  - A uranyl sulfate cluster in Na10[(UO2)(SO4)4](SO4)2.3H2O.
AB  - Decasodium uranyl hexasulfate trihydrate,
      Na(10)[(UO(2))(SO(4))(4)](SO(4))(2).3H(2)O, contains an unusual uranyl sulfate
      cluster with the composition [(UO(2))(SO(4))(4)](6-). The cluster is composed of
      a uranyl pentagonal bipyramid and four sulfate tetrahedra. Three sulfate
      tetrahedra are linked to the uranyl pentagonal bipyramid by the sharing of
      vertices, and the other shares an equatorial edge of the uranyl pentagonal
      bipyramid. The uranyl sulfate clusters occur in layers parallel to (010). The
      structure also contains two isolated symmetrically distinct sulfate tetrahedra,
      which also occur in layers parallel to (010). The uranyl sulfate clusters and
      isolated sulfate tetrahedra are linked through bonds to Na(+) cations, and by
      hydrogen bonding involving the water molecules.

PMID- 12205366
TI  - Dineodymium tritelluride, Nd2Te3.
AB  - From a single-crystal study, Nd(2)Te(3) is found to be isostructural with
      Gd(2)Te(3), crystallizing in the U(2)S(3) structure type. Each of the two non
      equivalent Nd atoms is surrounded by seven Te atoms, with the polyhedra best
      described as a seven-octahedron and a monocapped trigonal prism. All atoms lie on
      mirror planes.

PMID- 12205367
TI  - The superconductor (Tl,Hg,Ca)2(Ba,Sr)2(Ca,Sr,Tl)Cu2O7.6.
AB  - In the title 2212-type superconductor (thallium mercury calcium barium strontium
      copper oxide), which contains both Tl and Hg in the charge reservoir (CR), Sr is
      located at both alkali-earth (AE) metal sites. Ca enters the CR at the same time
      as Tl shares the smaller AE site, which increases the apical Cu-Cu distance
      significantly. The structure causes the superconducting Cu-O layers to become
      significantly puckered.

PMID- 12205368
TI  - Hexaaquacobalt(II) bis(hypophosphite) and hexaaquacobalt(II)/nickel(II)
      bis(hypophosphite).
AB  - The title compounds, hexaaquacobalt(II) bis(hypophosphite),
      [Co(H(2)O)(6)](H(2)PO(2))(2), and hexaaquacobalt(II)/nickel(II)
      bis(hypophosphite), [Co(0.5)Ni(0.5)(H(2)O)(6)](H(2)PO(2))(2), are shown to adopt
      the same structure as hexaaquamagnesium(II) bis(hypophosphite). The packing of
      the Co(Ni) and P atoms is the same as in the structure of CaF(2). The
      Co(II)(Ni(II)) atoms have a pseudo-face-centred cubic cell, with a = b
      approximately 10.3 A, and the P atoms occupy the tetrahedral cavities. The
      central metal cation has a slightly distorted octahedral coordination sphere. The
      geometry of the hypophosphite anion in the structure is very close to ideal, with
      point symmetry mm2. Each O atom of the hypophosphite anion is hydrogen bonded to
      three water molecules from different cation complexes, and each H atom of the
      hypophosphite anion is surrounded by three water molecules from further different
      cation complexes.

PMID- 12205369
TI  - The ordered hydrocerussite-type structure of (PbCO3)2.BaF2.
AB  - Single crystals of synthetic (PbCO(3))(2).BaF(2), bis[lead(II) carbonate] barium
      difluoride, have been grown under hydrothermal conditions. The compound
      crystallizes in the ordered hydrocerussite [(PbCO(3))(2).Pb(OH)(2)] structure and
      can be derived from a close packing of the metal atoms with a stacking sequence
      of [c(h)(2)](3) along the c axis. O and F atoms are situated approximately in the
      tetrahedral voids, resulting in the formation of a slightly distorted
      [BaF(6)O(6)] icosahedron and a [1+6+3]-coordinate Pb atom, with one short bond to
      F, six bonds to O and three longer bonds to additional O atoms. The carbonate
      group deviates only slightly from the geometry of an equilateral triangle.

PMID- 12205370
TI  - Bis[1-(pyridin-2-yl)ethanone-kappa N 4-phenylthiosemicarbazonato-kappa
      2N4,S]manganese(II).
AB  - One half of the molecule of the title complex, [Mn(C(14)H(13)N(4)S)(2)], is
      related to the other half by a twofold axis passing through the Mn atom. This
      high-spin Mn atom is six-coordinated, in an octahedral geometry, by the
      azomethine N, the pyridyl N and the thiolate S atom of two planar 1-(pyridin-2
      yl)ethanone N(4)-phenylthiosemicarbazone ligands. In the crystal, the molecules
      are interconnected by N-H.S and C-H.N interactions, forming a three-dimensional
      network.

PMID- 12205371
TI  - (Et4N)4[V4O12].2H2O.
AB  - The title compound, tetrakis(tetraethylammonium) cyclo-tetra-micro-oxo
      tetrakis[dioxovanadium(V)] dihydrate, (C(8)H(20)N)(4)[V(4)O(12)].2H(2)O, was
      obtained by reacting V(2)O(5) with (C(2)H(5))(4)NOH. It consists of a discrete
      centrosymmetric molecular anion, [V(4)O(12)](4-), where four tetrahedral VO(4)
      units share two vertices with each other to form a ring. A water molecule is
      attached on each side of the ring through hydrogen bonds.

PMID- 12205372
TI  - Chlorotris(2,4,6-trimethylphenyl)tin(IV) and its ethanol hemisolvate.
AB  - Chlorotris(2,4,6-trimethylphenyl)tin(IV), crystallizes from ethanol as solvent
      free needles, [Sn(C(9)H(11))(3)Cl], (I), and as the hemisolvate,
      [Sn(C(9)H(11))(3)Cl].0.5C(2)H(6)O, (II). The asymmetric unit in (I) has three
      independent molecules, whereas in (II), there are two [Sn(C(9)H(11))(3)Cl]
      molecules together with one ethanol molecule. In the unit cell of (II), the
      ethanol molecules lie in channels between stacks of (Mes)(3)SnCl molecules (Mes
      is 2,4,6-trimethylphenyl) and each ethanol molecule is disordered (0.50:0.50)
      over two positions. A comparison of the structures of the title compounds and
      other (Mes)(3)SnX (X = F, Br or I) systems with those of the triphenyltin
      analogues shows that the steric requirements of the o-CH(3) groups are met by a
      flattening of the SnC(3) skeleton and increases in the average Sn-X and Sn-C
      values. Comparing Sn-X data for (Mes)(3)SnX (X = F, Cl, Br or I) systems with
      values for the tris(o-methoxyphenyl)tin analogues suggests that the Sn-F distance
      of 1.961 A in (Mes)(3)SnF may well be characteristic of sterically unhindered
      four-coordinate Ar(3)SnF systems.

PMID- 12205373
TI  - Bis(5-hydroxy-2-hydroxymethyl-4-pyrone-kappa 2O4,O5)bis(2-hydroxymethyl-5-oxido-4
      pyrone-kappa 2O4,O5)calcium(II) tetrahydrate.
AB  - In the title compound, [Ca(C(6)H(5)O(4))(2)(C(6)H(6)O(4))(2)].4H(2)O, which is a
      kojic acid-Ca(2+) complex, the Ca atom is on a twofold axis and is
      octacoordinated by O atoms from four pyrone ligand molecules. The hydroxyl and
      ketone O atoms of each ligand form a five-membered chelate ring with the Ca atom.
      The crystal structure is stabilized by partial stacking and O-H.O hydrogen bonds.

PMID- 12205374
TI  - Tetrakis(mu-guanidinoacetic acid-kappa 2O:O')bis[(nitrato-kappa O)copper(II)].
AB  - The title compound, [Cu(2)(NO(3))(2)(C(3)H(7)N(3)O(2))(4)], forms a
      centrosymmetric dimer, with the two Cu(2+) ions separated by 2.6525 (6) A. The
      asymmetric unit contains a Cu atom coordinated to two guanidinoacetic acid
      ligands (via one carboxylate O atom from each ligand) and to a nitrate group. The
      inversion centre in P-1 generates the entire molecule, in which each Cu atom is
      coordinated to four carboxylate and to one nitrate O atom; ignoring the Cu-Cu
      separation, the geometry about each Cu atom is square pyramidal. The amino acid
      ligand is in the zwitterionic form. Strong N-H.O hydrogen bonds lead to a three
      dimensional supramolecular structure, in which the N.O distances are in the range
      2.931 (4)-3.278 (3) A, with N- H.O angles ranging from 128 to 170 degrees.

PMID- 12205375
TI  - 8-Hydroxyquinaldinic acid and its nickel(II) complex.
AB  - The molecules of 8-hydroxyquinolinium-2-carboxylate, C(10)H(7)NO(3), have a
      planar structure, in which the carboxyl group is ionized and the ring N atom is
      protonated. The derived nickel(II) complex, bis(8-hydroxyquinoline-2-carboxylato
      kappa(3)O(2),N,O(8))nickel(II) trihydrate, [Ni(C(10)H(6)NO(3))(2)].3H(2)O,
      contains an octahedral central Ni(II) ion coordinated by the hydroxyl O atom, the
      ring N atom and the carboxylate O atom of each of the two tridentate ligands,
      with a perpendicular orientation of the quinoline rings.

PMID- 12205376
TI  - Tetraaqua-1kappa4O-bis(epsilon -caprolactam-1kappa O)-mu-cyano-1:2kappa 2N:C
      pentacyano-2kappa 5C-iron(III)yttrium(III), a novel cyano-bridged dinuclear
      complex.
AB  - Using caprolactam as a ligand, the novel title cyano-bridged yttrium(III)
      ferricyanide complex, [Y(caprolactam)(2)(H(2)O)(4)Fe(CN)(6)] or
      [FeY(CN)(6)(C(6)H(11)NO)(2)(H(2)O)(4)], has been synthesized and structurally
      characterized. The Y atom is seven-coordinate and has approximately pentagonal
      bipyramidal stereochemistry, with water molecules occupying apical positions. Of
      the five ligands in equatorial positions, one is the N-bound bridging cyano
      group, and flanking this are two O-bound caprolactam moieties, which are markedly
      inclined towards the bridged ferricyanide moiety such that they partially envelop
      it. Water molecules occupy the remaining two equatorial positions. The Y-N-C-Fe-C
      N sequence of atoms lies on a crystallographic twofold axis and is therefore
      perfectly linear, which has not been observed previously in cyano-bridged
      bimetallic complexes.

PMID- 12205377
TI  - Polymeric (3-amino-2-chloropyridine)nitratosilver(I).
AB  - In the title compound [alternative name: poly[silver(I)-micro-(3-amino-2
      chloropyridine)-micro-nitrato]], [Ag(NO(3))(C(5)H(5)ClN(2))](n) the Ag(I) atom is
      in an irregular AgN(2)O(3) geometry, surrounded by one pyridyl N atom [Ag-N 2.283
      (5) A], one amine N atom [Ag-N 2.364 (6) A] and three O atoms from different
      nitrate ions [Ag-O 2.510 (6)-2.707 (6) A]. The Ag ions are bridged by the 3-amino
      2-chloropyridine ligands into helical chains. Adjacent uniform chiral chains are
      further interlinked through the NO(3) bridges into an interesting two-dimensional
      coordination network in the solid.

PMID- 12205378
TI  - [Cd[C2(COO)2](H2O)3].H2O, the first cadmium salt of acetylenedicarboxylic acid.
AB  - In catena-poly[[[triaquacadmium(II)]-micro-acetylenedicarboxylato
      kappa(4)O,O':O",O"'] hydrate], [[Cd(C(4)O(4))(H(2)O)(3)].H(2)O](n), the Cd(II)
      atom is coordinated by two bidentate carboxylate groups and three water
      molecules, thus forming a sevenfold coordination polyhedron with all atoms
      located on general sites. These polyhedra are connected by the bifunctional
      acetylenedicarboxylate ligands, forming zigzag chains running parallel to [120].
      Hydrogen bonds, which involve the non-coordinated water molecule, connect these
      chains to form a three-dimensional framework.

PMID- 12205379
TI  - Dibromo[5,10,15,20-tetrakis(4-methoxyphenyl)porphyrinato-kappa 4N]platinum(IV)
      chloroform acetonitrile solvate.
AB  - In the title compound, [PtBr(2)(C(48)H(36)N(4)O(4))].0.896CHCl(3).0.569CH(3)CN,
      the centrosymmetric metal complex is octahedral, with the porphyrin ring
      essentially planar and the Br atoms occupying axial positions. The two
      independent methoxyphenyl substituents are tilted at angles of 89.0 and 67.0
      degrees with respect to the porphyrin plane. The Pt-N distances are 2.035 (4) and
      2.036 (4) A and the Pt-Br distance is 2.4666 (6) A. Chloroform and acetonitrile
      solvent molecules, exhibiting substantial disorder, occupy positions between the
      porphyrin molecules. This is the first crystal and molecular structure of a
      Pt(IV)-porphyrin complex to be reported.

PMID- 12205380
TI  - A comparative analysis of mono- and disaccharide benzyl fucopyranosides.
AB  - The syntheses and X-ray analyses of two fucopyranosides, the monosaccharide
      benzyl 3,4-di-O-acetyl-2-hydroxy-beta-D-fucopyranoside, C(17)H(22)O(7), and the
      disaccharide 1-benzyl O-(2,3-di-O-acetyl-4,6-O-benzylidene-beta-D-glucopyranosyl)
      (1-->2)-3,4-O-isopropylidene-beta-D-fucopyranoside, C(33)H(40)O(12), are
      described. The different substituents induce small conformational changes on the
      fucopyranoside ring. However, the conformation of the benzyl group varies from
      (+)gauche for the monosaccharide to synperiplanar for the disaccharide.

PMID- 12205381
TI  - L-Tryptophan formic acid solvate at 183 K.
AB  - In the title compound, C(11)H(12)N(2)O(2).CH(2)O(2), at 183 K. L-tryptophan
      appears in the zwitterionic form, while the formic acid molecule is neutral. The
      formic acid molecule is the donor in a strong O-H.O hydrogen bond to the
      carboxylate group of the tryptophan molecule, with a short O.O contact of 2.487
      (2) A.

PMID- 12205382
TI  - 11-Methyl-12a-phenyl-9a,12a-dihydrophenanthro[9',10:5,6][1,4]dioxino[2,3
      d]thiazole.
AB  - In the title compound, C(24)H(17)NO(2)S, the dioxine and thiazoline rings are
      distorted from planarity towards a half-chair and an envelope conformation,
      respectively. The configurations of the dioxine ring, the thiazoline ring and the
      attached phenyl ring are conditioned by the sp(3) state of the two bridgehead C
      atoms. The phenanthrene system is nearly coplanar with the dioxine ring, while
      the attached phenyl ring is orthogonal to the thiazoline ring.

PMID- 12205383
TI  - Orthorhombic polymorphs of two trans-4-aminoazoxybenzenes.
AB  - The two isomeric compounds 4-amino-ONN-azoxybenzene [or 1-(4-aminophenyl)-2
      phenyldiazene 2-oxide], i.e. the alpha isomer, and 4-amino-NNO-azoxybenzene [or 2
      (4-aminophenyl)-1-phenyldiazene 2-oxide], i.e. the beta isomer, both
      C(12)H(11)N(3)O, crystallized from a polar solvent in orthorhombic space groups,
      and their crystal and molecular structures have been determined using X-ray
      diffraction. There are no significant differences in the bond lengths and valence
      angles in the two isomers, in comparison with their monoclinic polymorphs.
      However, the conformations of the molecules are different due to rotation along
      the Ar-N bonds. In the alpha isomer, the benzene rings are twisted by 31.5 (2)
      and 14.4 (2) degrees towards the plane of the azoxy group; the torsion angles
      along the Ar-N bond in the beta isomer are 24.3 (3) and 23.5 (3) degrees. Quantum
      mechanical calculations indicate that planar conformations are energetically
      favourable for both isomers. The N-H.O hydrogen bonds observed in both networks
      may be responsible for the deformation of these flexible molecules.

PMID- 12205384
TI  - 1,4-Bis[(1-methyl-1-phenylethyl)peroxymethyl]benzene.
AB  - The title compound, C(26)H(30)O(4), is one of the first alkyl bis-peroxides to be
      structurally characterized. The molecule lies on a centre of inversion and
      therefore the terminal phenyl rings are parallel. Although there are three
      aromatic rings in the molecule, the C-O-O-C torsion angle of 163.10 (10) degrees
      is close to the value found in Me(3)COOCMe(3).

PMID- 12205385
TI  - N,N'-Dithiobisphthalimide-nitrobenzene (2/1): a Pn solvate with localized solvent
      molecules ordered head-to-tail in channels.
AB  - N,N'-Dithiobisphthalimide crystallizes from nitrobenzene solution as a solvate,
      2C(16)H(8)N(2)O(4)S(2).C(6)H(5)NO(2), having space group Pn. The bisphthalimide
      molecules are linked by C-H.O hydrogen bonds and by aromatic pi-pi-stacking
      interactions, forming a framework enclosing continuous channels running along the
      [100] direction and accounting for ca 20% of the unit-cell volume. The
      nitrobenzene molecules lie in these channels, ordered in a head-to-tail fashion
      and linked to the bisphthalimide framework by C-H.O and C-H.pi(arene) hydrogen
      bonds.

PMID- 12205386
TI  - The low-temperature phase of diisopropylammonium bromide.
AB  - The title compound, C(6)H(16)N(+).Br(-), was refined against room-temperature
      data in space group P2(1) as a racemic twin by Kociok-Kohn, Lungwitz & Filippou
      [Acta Cryst. (1996). C52, 2309-2311]. At low temperature, we found a different
      phase, which is characterized by a different cell (twice as big as the cell at
      room temperature) and a different space group (P2(1)/n). Surprisingly, the cell
      parameters obtained at low temperature can be transformed into those measured at
      ambient temperature. Even the coordinates can be transformed and the structure
      can be refined in the small cell. However, some warning signs (e.g. a low |E(2) -
      1| value, apparent twinning and peaks in the electron-density map) point to the
      correct cell and space group.

PMID- 12205387
TI  - The stable inner salt 2,2-dimorpholino-2-ethylium-1-dithioate.
AB  - The title compound, C(10)H(16)N(2)O(2)S(2), is considered to maintain an inner
      salt structure in the crystal, where the planes of the carbenium and the
      thiocarboxylate moieties are nearly perpendicular to each other [77 (2) degrees
      ], and the backbone C-C bond length [N(2)C-CS(2) 1.510 (2) A] is significantly
      shorter than a normal C-C single-bond length.

PMID- 12205388
TI  - 2,3-Dihydro-3,3-dimethylspiro[1H-4-oxanthracene-5,2'-oxiran]-10(5H)-one.
AB  - The central six-membered ring in the title compound, C(16)H(16)O(3), is almost
      planar (and almost coplanar with the aromatic ring), despite one of its C atoms
      being formally sp(3) hybridized. The planarity is a consequence of the C atom at
      the centre of the spirocyclic system also being part of the three-membered
      epoxide ring. The molecules are linked by pi-pi and C-H.pi interactions.

PMID- 12205389
TI  - 3,6,13,16-Tetrabromo-2,7,12,17-tetrapropylporphycene.
AB  - The title compound [systematic name: 3,10,13,20-tetrabromo-4,9,14,19-tetrapropyl
      21,22,23,24-tetraazapentacyclo[16.2.1.1(2,5).1(8,11).1(12,15)]tetracosa
      2(22),3,5,7,9,11,13,15(24),16,18,20-undecaene], C(32)H(34)Br(4)N(4), crystallizes
      in two distinct crystalline forms, viz. monoclinic prisms and triclinic plates,
      and the first of these is described here. The molecule of the prismatic form has
      a centre of symmetry and a more warped structure than that of the triclinic plate
      like form. The shape of the central N(4) cavity is rectangular, enlarged in the
      direction of the methine-bridge C atoms, and the N.N distances are 2.713 (3) and
      2.818 (3) A.

PMID- 12205390
TI  - 1,1'-Di(hydrazinocarbonylmethyl)-2,2'-biimidazole monohydrate and 1,1'-di[2
      (hydrazinocarbonyl)ethyl]-2,2'-biimidazole.
AB  - The crystal structures of the title compounds, alternatively called 2,2'-(2,2'
      biimidazole-1,1'-diyl)diacetohydrazide monohydrate, C(10)H(14)N(8)O(2).H(2)O,
      (I), and 3,3'-(2,2'-biimidazole-1,1'-diyl)dipropionohydrazide,
      C(12)H(18)N(8)O(2), (II), respectively, have been determined. The molecules
      consist of half-molecule asymmetric units related by a twofold rotation in (I)
      and by a center of inversion in (II). The imidazole rings of both molecules
      crystallize in a nearly coplanar fashion [dihedral angles of 5.91 (3) and 0.0 (1)
      degrees for (I) and (II), respectively]. Both planar hydrazinocarbonylalkyl
      substituents are essentially planar and assume the E orientation.

PMID- 12205391
TI  - 5-Methyl-2-thiouracil.
AB  - The molecular structure of the title compound, also known as 2-thiothymine
      [systematic name: 2,3-dihydro-5-methyl-2-thioxopyrimidin-4(1H)-one],
      C(5)H(6)N(2)OS, is similar to that of thymine, with only small changes in the
      ring structure, apart from a significant difference at the substitution site [S=C
      = 1.674 (1) A]. The molecules are connected by hydrogen bonds, with N-H.O = 2.755
      (2) A and N-H.S = 3.352 (1) A. The hydrogen-bond network is different from that
      in thymine, since it involves all the donor and acceptor atoms.

PMID- 12205392
TI  - 2-Methyl-1-phenylsulfanyl-1,2-dicarba-closo-dodecaborane(12).
AB  - In the title o-carborane derivative, C(9)H(18)B(10)S, the methyl and
      phenylsulfanyl groups are connected to the C atoms of the carborane cage. The
      C(cage)-C(cage) distance is 1.708 (4) A.

PMID- 12205393
TI  - Ethyl 4-dodecyl-3,5-dimethyl-1H-pyrrole-2-carboxylate: intermolecular
      interactions in an amphiphilic pyrrole.
AB  - The title compound, C(21)H(37)NO(2), is a new amphiphilic pyrrole with a long
      hydrocarbon chain, which will be used as a precursor for the synthesis of
      Langmuir-Blodgett films of porphyrins. Molecules related by an inversion centre
      are joined head-to-head into dimers by strong N-H.O hydrogen bonds. The dimers
      pack in the structure with their carbon chains parallel to one another, thereby
      forming alternating layers of carbon chains and pyrrole heads. The structure is
      further stabilized by two weak C-H.pi intermolecular interactions, thereby
      saturating the hydrogen-bonding capability of the aromatic pi-electron clouds.

PMID- 12205394
TI  - Hydrogen-bonded assemblages in 2,6-bis(hydroxymethyl)-4-R-phenol, with R =
      methyl, methoxy, phenoxy and 1-(4-methoxyphenyl)-1-methylethyl.
AB  - Four derivatives of 2,6-bis(hydroxymethyl)phenol, with various para substituents,
      have been investigated; these are 2,6-bis(hydroxymethyl)-4-methylphenol,
      C(9)H(12)O(3), (I), 2,6-bis(hydroxymethyl)-4-methoxyphenol, C(9)H(12)O(4), (II),
      2,6-bis(hydroxymethyl)-4-phenoxyphenol, C(14)H(14)O(4), (III), and 2,6
      bis(hydroxymethyl)-4-[1-(4-methoxyphenyl)-1-methylethyl]phenol, C(18)H(22)O(4),
      (IV). All four structures display hydrogen-bonding networks resulting in sheets,
      with possible weak inter-sheet pi-pi interactions in one case. In all the
      structures but one, the molecules form centrosymmetric dimeric subunits held
      together by two hydrogen bonds between the hydroxymethyl groups and, in two
      cases, by probable pi-pi interactions.

PMID- 12205395
TI  - 4,10-Dinitro-2,6,8,12-tetraoxa-4,10-diazaisowurtzitane (TEX): a nitramine with an
      exceptionally high density.
AB  - The title compound (systematic name: 4,10-dinitro-2,6,8,12-tetraoxa-4,10
      diazatetracyclo[5.5.0.0(3,11).0(5,9)]dodecane), C(6)H(6)N(4)O(8), exhibits the
      highest density among known N-nitramines, due to its close-packed crystal
      structure. It may be regarded as consisting of a distorted hexagonal close-packed
      lattice formed by the isowurtzitane cages, with the nitro groups occupying the
      free space between the cages.

PMID- 12205396
TI  - 3,6-Bis(dimethylamino)-10-(10-iododecyl)acridinium iodide.
AB  - In the title compound, C(27)H(39)IN(3)(+).I(-), the acridinium system shows the
      usual approximate mirror symmetry about the central C.N line, and the
      corresponding bond lengths and angles in the two halves agree within experimental
      error. The alkyl chain at the ring N atom is initially perpendicular to the ring
      plane and then bends sharply at the fourth C atom. Pairs of centrosymmetrically
      related cations overlap two of their rings and the dimethylamino groups are also
      partly involved in the overlap. Each I(-) ion is involved in short-range
      interactions with two cations. These interactions give rise to a 14-membered
      cyclic structure, which involves pairs of cations and anions across an inversion
      centre.

PMID- 12205397
TI  - Ethyl 5-[2-(2-aminophenylimino)-2-phenylethylidene]-4-(4-chlorophenyl)-4,5
      dihydro-1,3,4-thiadiazole-2-carboxylate et ethyl 5-[2-[2
      (methylamino)phenylimino]-2-phenylethylidene]-4-(4-nitrophenyl)-4,5-dihydro-1,3,4
      thiadiazole-2-carboxylate.
AB  - Condensation of N-aryl-C-(ethoxycarbonyl)nitrilimines with 4-phenyl-1,2-dihydro
      3H-1,5-benzodiazepine-2-thione lead to the title compounds,
      C(25)H(21)ClN(4)O(2)S, (IIIa), and C(26)H(23)N(5)O(4)S, (IIIb), respectively.
      Crystals of both compounds were obtained by evaporation of ethanol solutions at
      room temperature. In the structures of both compounds, a non-bonding interaction
      is observed between the S atom and the imino N atom. It is established that 1,3
      dipolar cycloaddition occurs on the C=S double bond of the 1,5-benzodiazepine-2
      thione.

PMID- 12205398
TI  - The ternary complex 4-(2-pyridyl)pyridinium-3,5-dinitrobenzoate-3,5
      dinitrobenzoic acid (1/1/1).
AB  - In the title ternary complex, C(10)H(9)N(2)(+).C(7)H(3)N(2)O(6)(
      ).C(7)H(4)N(2)O(6), the pyridinium cation adopts the role of the donor in an
      intermolecular N-H.O hydrogen-bonding interaction with the carboxylate group of
      the 3,5-dinitrobenzoate anion. The molecules of the ternary complex form
      molecular ribbons perpendicular to the b direction, which are stabilized by one N
      H.O, one O-H.O and five C-H.O intermolecular hydrogen bonds. The ribbons are
      further interconnected by three intermolecular C-H.O hydrogen bonds into a three
      dimensional network.

PMID- 12205399
TI  - Genetics and the pathogenesis of adult respiratory distress syndrome.
AB  - Most human diseases are substantially affected by genetic factors. It now seems
      clear that the pathogenesis of most diseases lies in complex interactions among
      the genotype, the environment, and the nature of the process that leads to cell,
      tissue, organ, or systemic injury. The information derived from the knowledge of
      the recent completion of the human genome, when combined with the sophisticated
      tools of molecular biology, will provide the framework for more rapid
      identification of the genes responsible for susceptibility to disease. Genetic
      approaches to complex disorders offer great potential to improve our
      understanding of their pathophysiology, but they also offer significant
      challenges. There is evidence that cellular and humoral immune responses are
      subject to polymorphic genetic control, which could explain the well-known
      diversity of clinical manifestations and outcomes in critically ill patients with
      the same disease. Therefore, genetic differences between people may affect the
      likelihood of the development of diseases. Markers of susceptibility will
      indicate differences in individuals or populations that affect the body's
      response. The underlying principle of susceptibility markers is the
      interindividual differences that confer sensitivity or resistance to
      environmentally induced diseases. This article reviews some of those
      susceptibility factors for critical illness and acute lung injury.

PMID- 12205400
TI  - Role of reactive oxygen and nitrogen species in acute respiratory distress
      syndrome.
AB  - Reactive oxygen species are reactive, partially reduced derivatives of molecular
      oxygen (O 2 ). Important reactive oxygen species in biologic systems include
      superoxide radical anion, hydrogen peroxide, and hydroxyl radical. Closely
      related species include the hypohalous acids, particularly hypochlorous acid;
      chloramine and substituted chloramines; and singlet oxygen. Reactive nitrogen
      species are derived from the simple diatomic gas, nitric oxide. Peroxynitrite and
      its protonated form, peroxynitrous acid, are the most significant reactive
      nitrogen species in biologic systems. A variety of enzymatic and nonenzymatic
      processes can generate reactive oxygen species and reactive nitrogen species in
      mammalian cells. An extensive body of experimental evidence from studies using
      animal models supports the view that reactive oxygen species and reactive
      nitrogen species are important in the pathogenesis of acute respiratory distress
      syndrome. This view is further supported by data from clinical studies that
      correlate biochemical evidence of reactive oxygen species-mediated or reactive
      nitrogen species-mediated stress with the development of acute respiratory
      distress syndrome. Despite these data, pharmacologic strategies directed at
      minimizing reactive oxygen species-mediated or reactive nitrogen species-mediated
      damage have yet to be successfully introduced into clinical practice. The most
      extensively studied compound in this regard is N -acetylcysteine; unfortunately,
      clinical trials with this compound in patients with acute respiratory distress
      syndrome have yielded disappointing results.

PMID- 12205401
TI  - Ventilator-induced lung injury.
AB  - The clinical relevance of experimental ventilator-induced lung injury has
      recently received a resounding illustration by the Acute Respiratory Distress
      Syndrome Network trial that showed a 22% reduction of mortality in patients with
      acute respiratory disease syndrome when lung mechanical stress was lessened by
      tidal volume reduction during mechanical ventilation. This clinical confirmation
      of the concept of ventilator-induced lung injury has also undisputedly
      substantiated the experimental observation that excessive tidal volume and/or end
      inspiratory lung volume is the main determinant of ventilator-induced lung
      injury. More recently, attention has focused on the roles and implication in the
      pathogenesis of ventilator-induced lung injury of inflammatory cells and
      mediators that may be activated and released either in the alveolar space or in
      the systemic circulation because of the rupture of the alveolar-capillary barrier
      and on the cellular response to mechanical stress.

PMID- 12205402
TI  - Pulmonary versus extrapulmonary acute respiratory distress syndrome: different
      diseases or just a useful concept?
AB  - The acute respiratory distress syndrome may complicate both pulmonary and
      extrapulmonary conditions. There is a growing belief that the predisposition to,
      and clinical course of, the syndrome may be influenced by the extent to which the
      lung is directly involved in the precipitating pathologic changes. Several
      studies have highlighted differences in morphology and respiratory physiology
      between the two subgroups in the early stages of acute respiratory distress
      syndrome. Further, preliminary reports have suggested that the effects of
      therapeutic interventions such as alterations in positive end-expiratory
      pressure, prone ventilation, and the use of inhaled vasoactive agents may differ
      between pulmonary and extrapulmonary acute respiratory distress syndrome. There
      are, however, inconsistencies between various studies addressing these issues,
      which may relate in part to differences in etiologic case mix. There are also
      practical difficulties in assigning certain cases to one of these two groups.
      Finally, there are as yet no outcome data to support any modification of clinical
      management on the basis of this distinction.

PMID- 12205403
TI  - Recent advances in the clinical application of heart-lung interactions.
AB  - Clinical applications of heart-lung interactions have centered on the impact of
      ventilation on regional blood flow and the measures of cardiovascular
      responsiveness to both positive end-expiratory pressure and fluid resuscitation.
      These new and exciting applications of established physiology provide new
      therapeutic options for the caregiver with reduced risk for complications in the
      patient. This review illustrates several of these studies within the context of
      known cardiopulmonary physiology.

PMID- 12205404
TI  - Reinterpreting the pressure-volume curve in patients with acute respiratory
      distress syndrome.
AB  - New evidence requires a reinterpretation of the inflation pressure-volume curve
      and suggests that neither the lower nor the upper inflection point provides
      reliable information to determine safe ventilator settings in the acute
      respiratory distress syndrome. Recruitment probably continues throughout the
      inflation pressure-volume curve, and studies of the deflation pressure-volume
      curve, reinflations after partial deflation, or decremental positive end
      expiratory pressure trials after a recruitment maneuver are probably needed to
      determine open-lung positive end-expiratory pressure.

PMID- 12205405
TI  - Gas exchange in the ventilated patient.
AB  - Increased knowledge of the pathophysiologic mechanisms of impaired gas exchange
      during acute respiratory failure during recent years has stimulated many studies
      that evaluate different treatments to improve oxygenation and outcome. Changes in
      body position (mainly prone positioning) can significantly improve gas exchange
      in patients with acute respiratory distress syndrome and acute lung failure, with
      few complications related to the maneuver; however, no survival advantage has yet
      been detected. A correlation between aerated lung tissue and oxygenation also
      confirms the importance of recruitment maneuvers in improving gas exchange.
      Recent suggestions that recruitment of alveoli proceeds during most of the
      inspired vital capacity and not only around the lower inflection point of the
      pressure-volume curve raises the question how to best perform recruitment
      maneuvers. New data support the hypothesis that maintenance of even small amount
      of spontaneous breathing during mechanical ventilation (with airway pressure
      release ventilation or biphasic positive airway pressure) can improve gas
      exchange, whereas other unconventional ventilatory modes have not yet proved
      advantageous. Some mechanisms responsible for the high percentage of nonresponse
      to inhaled nitric oxide have recently been proposed, and combinations of inhaled
      nitric oxide with other therapies have been tested. Increased knowledge in this
      area may, in the future, make inhaled nitric oxide more attractive in the
      treatment of adult respiratory failure as well as in neonatal intensive care.

PMID- 12205406
TI  - Reduced tidal volumes and lung protective ventilatory strategies: where do we go
      from here?
AB  - Three major determinants of lung injury associated with mechanical ventilation
      have been clearly identified: high pressure/high volume, the shear forces caused
      by intratidal collapse and decollapse leading to barotrauma/volotrauma/biotrauma.
      The lung protective strategy aims to reduce the impact of all three determinants.
      A groundbreaking study showed that reduced tidal volume is less dangerous than
      high tidal volume, but the researchers did not apply "full" lung protective
      strategy and did not take into account the shear forces. "Full" protective lung
      strategy was tested in only one study and in a limited number of patients.
      Several physiologic studies strongly suggest the advantages of the lung
      protective strategy.

PMID- 12205407
TI  - Controlled versus assisted mechanical ventilation.
AB  - On the basis of currently available data, it can be suggested that maintained
      spontaneous breathing during mechanical ventilation should not be suppressed even
      in patients with severe pulmonary dysfunction if no contraindications, such as
      increased intracranial pressure, are present. Improvements in pulmonary gas
      exchange, systemic blood flow, and oxygen supply to tissues, which have been
      observed when spontaneous breathing was allowed during ventilatory support, are
      reflected in the clinical improvement in the patient's condition, as indicated by
      significantly fewer days with ventilation, earlier extubation, and shorter stays
      in the intensive care unit. The positive effects of spontaneous breathing have
      been documented only for some of the available partial ventilatory support
      modalities. If ventilatory modalities are limited to those whose positive effects
      have been documented, then partial ventilatory support can be used as a primary
      modality even in patients with severe pulmonary dysfunction. Whereas controlled
      mechanical ventilation followed by weaning with partial ventilatory support
      modalities has been the earlier standard in ventilation therapy, this approach
      should be reconsidered in view of the available data.

PMID- 12205408
TI  - Prevention and management of ventilator-associated pneumonia.
AB  - Worldwide, the increasing rates of microbial resistance represent a serious
      public health problem. Therefore, measures to prevent ventilator-associated
      pneumonia gain increasing importance. Because antimicrobial treatment in the ICU
      is a major source of microbial resistance, prevention should be understood not
      only as the sum of preventive measures but also as part of any management
      strategy. In this year of review, several important contributions have been made
      to a better understanding of the relative role of preventive measures. This is
      particularly true of noninvasive ventilation, continuous aspiration of subglottic
      secretions, and closed endotracheal suctioning. Management strategies for
      ventilator-assisted pneumonia remain highly controversial. Despite two decades of
      vigorous research, there is still no evidence that invasive bronchoscopic
      techniques should form part of a routine approach to suspected ventilator
      assisted pneumonia. Moreover, an impact in terms of important outcome variables
      could not be consistently demonstrated. In the authors' view, the controversy
      regarding the relative validity of diagnostic tools should end, and the focus
      should shift to strategies that define low-risk patients with suspected
      ventilator-assisted pneumonia who can safely be treated by short-term
      monotherapy. Finally, several contributions have refined the established
      treatment regimen. Several new drugs for the treatment of ventilator-assisted
      pneumonia caused by Gram-positive multiresistant pathogens have been evaluated
      with promising results.

PMID- 12205409
TI  - Ventilation of patients with asthma and chronic obstructive pulmonary disease.
AB  - Ventilatory intervention is often life-saving when patients with asthma or
      chronic obstructive pulmonary disease (COPD) experience acute respiratory
      compromise. Although both noninvasive and invasive ventilation methods may be
      viable initial choices, which is better depends upon the severity of illness, the
      rapidity of response, coexisting disease, and capacity of the medical
      environment. In addition, noninvasive ventilation often relieves dyspnea and
      hypoxemia in patients with stable severe COPD. On the basis of current evidence,
      the general principles of ventilatory management common to patients with acutely
      exacerbated asthma/COPD are these: noninvasive ventilation is suitable for a
      relatively simple condition, but invasive ventilation is usually required in
      patients with more complex or more severe disease. It is crucial to provide
      controlled hypoventilation, longer expiratory time, and titrated extrinsic
      positive end-expiratory pressure to avoid dynamic hyperinflation and its
      attendant consequences. Controlled sedation helps achieve synchrony of
      triggering, power, and breath timing between patient and ventilator. When
      feasible, noninvasive ventilation often facilitates the weaning of ventilator
      dependent patients with COPD and shortens the patient's stay in the intensive
      care unit.

PMID- 12205411
TI  - Overview of bone morphogenetic proteins.
AB  - STUDY DESIGN: A literature review was conducted. OBJECTIVES: To review the
      discovery of the bone morphogenetic proteins and describe the bone morphogenetic
      protein products that will or may be available for clinical use. SUMMARY OF
      BACKGROUND DATA: Bone morphogenetic proteins comprise the osteoinductive
      component of several tissue engineering products in late-stage development as
      replacements for autogenous bone graft, and for bone augmentation and repair.
      METHODS: The literature on bone morphogenetic proteins was reviewed. RESULTS:
      Bone morphogenetic proteins were discovered originally on the basis of their
      presence in osteoinductive extracts of bone matrix. Molecular cloning of bone
      morphogenetic proteins demonstrated that they are a family of related
      differentiation factors, each capable of inducing the formation of new bone
      tissue when implanted. Two of the molecules in clinical use, recombinant human
      bone morphogenetic protein-2 and recombinant human bone morphogenetic protein-7
      (OP-1) are produced in a biotechnology process using recombinant deoxyribonucleic
      acid technology that offers unlimited supply and substantial control over purity
      and reproducible activity. A third material, bovine bone morphogenetic protein
      extract, is extracted from bone, and contains a mixture of bone morphogenetic
      protein molecules. Each of these molecules, although osteoinductive in vivo, has
      different physiologic roles and biologic activities in vivo and in vitro.
      Successful development of a product for use in spinal fusion involves selecting
      the osteoinductive molecule, the amount of the bone morphogenetic protein
      required, and the method of delivery, as well as conducting subsequent
      preclinical and clinical studies to evaluate its efficacy and safety.
      CONCLUSIONS: On the basis of the data provided in this issue of Spine, some of
      these bone morphogenetic protein-based products provide for revolutionary
      therapies in orthopedic practice.

PMID- 12205413
TI  - Mechanism for the action of bone morphogenetic proteins and regulation of their
      activity.
AB  - Although the bone morphogenetic proteins (BMPs) are multifunctional proteins,
      implantation of osteogenic BMPs such as BMP-2 and BMP-7 at an osseous or
      extraosseous site results in bone and cartilage formation. These molecules are
      soluble, local-acting signaling proteins, which bind to specific receptors on the
      surface of the cell. The receptors then transduce the signal via a group of
      proteins called Smads, which in turn activate particular genes. In vivo, these
      BMPs act primarily as differentiation factors, turning responsive mesenchymal
      cells into cartilage- and bone-forming cells. A summary of the in vitro and in
      vivo studies suggests that implantation of these BMPs stimulates cells from the
      soft and hard tissues (e.g., muscle, bone marrow, periosteum) to become bone, and
      in some cases, cartilage forming cells. The activity of BMPs is tightly
      controlled at many levels. The tissue-specific transcription factor (basic helix
      loop-helix factor) and its binding sequence (E-box) together play a critical role
      in deciding the expression of BMPs. Outside the cell, soluble inhibitory proteins
      such as noggin, chordin, and follistatin can bind certain of the BMPs and inhibit
      their binding to cell surface receptors. Inside the cell, the activity of BMPs is
      controlled through the combination of signal-transducing and inhibitory Smad
      proteins. Bone morphogenetic proteins can upregulate expression of the inhibitory
      Smad proteins. These Smads are phosphorylated and translocate into the nucleus,
      where they regulate the transcription of target genes together with other
      transcription factors including PEBP2alphaA/Cbfa1. Cooperation between
      PEBP2alphaA/Cbfa1 and BMP-activated Smad (Smad1/5) in the nucleus induces the
      expression of the genes related to the osteoblast phenotype. In addition, a
      number of negative regulators of BMP action exist within the nucleus. All of
      these regulatory mechanisms together cause the bone-induction process to be
      controlled tightly and self-limiting. Thus, bone induction is observed only
      locally at the site of BMP and matrix implantation, as defined by the volume of
      matrix, and it is limited temporally only to the time when the BMP is present.

PMID- 12205414
TI  - Bone morphogenetic protein delivery systems.
AB  - STUDY DESIGN: A review was conducted. OBJECTIVES: To review the rationale for the
      use of carrier systems to deliver bone morphogenetic proteins to sites of
      orthopedic repair, and to discuss commonly used carriers. SUMMARY OF BACKGROUND
      DATA: Carriers for bone morphogenetic protein in spine fusion are used to
      increase the retention of these osteogenic factors at the treatment site, and to
      serve as an osteoconductive matrix for bone forming cells while maintaining a
      space or volume in which bone formation can occur. METHODS: The literature is
      reviewed and discussed. RESULTS: Although bone morphogenetic proteins can induce
      bone formation when delivered in formulation buffer in small animal models,
      carriers often are used in larger animal models and human clinical trials to
      maintain the concentration of osteogenic factors at the treatment site for a
      sufficient period to allow bone-forming cells to migrate to the area of injury
      and to proliferate and differentiate. For spine fusion, carriers also are
      required to serve as an osteoconductive matrix for bone-forming cells while
      maintaining a space or volume in which bone formation can occur. Four major
      categories of carrier materials are used for osteogenic factor delivery:
      inorganic materials, synthetic polymers, natural polymers, and composites of the
      first three materials. In addition, allograft bone has been used to deliver
      osteogenic factors to the site of orthopedic repairs. The efficacy of osteogenic
      carrier combinations often is site specific and species specific. The requirement
      for supraphysiologic concentrations of osteogenic factors may be related to the
      ability of the delivery system to increase the retention time at the treatment
      site and overcome tight regulation of these factors by their inhibitors. Dose
      escalation in large animal models also may be related to a decrease in the number
      of responding cells and a slower rate of bone formation. New delivery systems
      being evaluated include depot delivery systems, viral vector systems, conjugated
      osteogenic factor delivery systems, and oral small molecule targets. CONCLUSIONS:
      Delivery systems play an important role in the use of osteogenic factors to
      augment spine fusions and other orthopedic repairs.

PMID- 12205416
TI  - Overview of the biology of lumbar spine fusion and principles for selecting a
      bone graft substitute.
AB  - STUDY DESIGN: Reviews were conducted. OBJECTIVES: To review the biology of spine
      fusion healing, and to outline several fundamental principles required for the
      selection of a bone graft substitute. SUMMARY OF BACKGROUND DATA: More than
      200,000 spine fusions are performed each year in the United States. The success
      of this procedure is limited by morbidity from iliac crest bone graft harvest and
      a nonunion rate that ranges from 10% to 40%. In recent years, there has been an
      increased understanding of the biology of spine fusion healing. In addition,
      there has been a focus on finding suitable substitutes for autogenous iliac crest
      bone graft to promote spine fusion. The selection of a specific bone graft
      substitute can be a daunting task for the surgeon. METHODS: The available
      literature was reviewed and combined with the author's personal experience.
      RESULTS: A basic understanding of the biology of healing in different types of
      spine fusions and the differences between different categories of bone graft
      substitutes can help surgeons organize the graft selection process. CONCLUSIONS:
      In general, purely osteoconductive substitutes are less effective in adult
      posterolateral spine fusions, but may be suitable in the anterior spine when it
      is rigidly immobilized. Osteoinductive substitutes are more likely to be
      successful as extenders, enhancers, or substitutes for posterolateral spine
      fusion.

PMID- 12205417
TI  - Animal models for preclinical assessment of bone morphogenetic proteins in the
      spine.
AB  - STUDY DESIGN: A review of the rationale behind the use of animal models for the
      assessment of bone morphogenetic proteins (BMPs) in the spine. OBJECTIVE: To
      summarize the underlying principles of animal experimentation in the context of
      bone morphogenetic proteins and the spine. SUMMARY OF BACKGROUND DATA: Animal
      models aid in the collection of important information regarding the precise
      mechanobiologic events that occur during spinal fusion healing. Reproducible
      spinal fusion models have been developed in several animal species, leading to
      experimentation in a controlled fashion. Reliable assessment of outcome measures
      for osseous healing, including histology and biomechanical testing, has made
      preclinical testing of innovative growth factors essential before the advance to
      clinical trials. METHODS: These materials have initially gone through the "burden
      of proof" steps: proof of concept studies, feasibility studies, and efficacy
      studies. RESULTS AND CONCLUSIONS: Bone morphogenetic proteins have undergone
      extensive scrutiny in the preclinical arena. This article summarizes the
      evolution of animal experimentation with BMP including the background and future
      directions.

PMID- 12205419
TI  - Safety profile for the clinical use of bone morphogenetic proteins in the spine.
AB  - STUDY DESIGN: A review was conducted. OBJECTIVE: To determine the safety profiles
      of human recombinant bone morphogenetic protein-2 (rhBMP-2) and osteogenic
      protein-1 (OP-1) used clinically in spine applications. SUMMARY OF BACKGROUND
      DATA: Safety issues associated with the use of bone morphogenetic proteins in
      spine applications include the possibility of bony overgrowth, interaction with
      exposed dura, cancer risk, systemic toxicity, reproductive toxicity,
      immunogenicity, local toxicity, osteoclastic activation, and effects on distal
      organs. These issues have been given detailed examination in both human and
      animal studies, and safety data are available for both rhBMP-2 and OP-1. The
      safety data available for OP-1 are less detailed. METHODS: The study involved
      reviews of published reports and the safety data submitted to the Food and Drug
      Administration (rhBMP-2 and OP-1) and to the European Agency for the Evaluation
      of Medicinal Products (OP-1), as well as personal communication with the
      manufacturers of rhBMP-2 (Medtronic Sofamore Danek, Memphis, TN) and OP-1
      (Stryker Biotech, Hopkinton, MA). RESULTS: Application of either rhBMP-2 or OP-1
      to raw decorticated bony surfaces leads to new bone formation, which is desirable
      in the intertransverse or interbody regions. However, new bone formation also may
      occur if rhBMP-2 or OP-1 comes in contact with laminectomy sites or decompressed
      neuroforamina, and may lead to restenosis. Inadvertent placement of either rhBMP
      2 or OP-1 in the spinal canal leads to formation of bone. Leakage of rhBMP-2 or
      OP-1 outside the fusion area may lead to adjacent-level fusion. Accurate
      placement of these factors and adequate retention by their carrier are highly
      important factors in minimizing these problems. Subdural bone formation occurs if
      OP-1 is implanted directly beneath the dura. Osteoclastic overstimulation does
      not appear to be a significant problem with rhBMP-2. However, bone resorption has
      been associated with OP-1 used in the setting of thoracolumbar fractures.
      Findings show that RhBMP-2 has an antiproliferative effect on many cancer cells,
      and no evidence exists that it is carcinogenic. It is unlikely that OP-1 has
      carcinogenic potential, although fewer data are available. Systemic and local
      toxicity, significant adverse effects, and harmful effects on distant organs have
      not been observed in either human or animal studies on rhBMP-2 and OP-1. The
      benign safety profile of rhBMP-2 may result from its rapid systemic clearance,
      which results in very little systemic exposure. Systemic exposure to OP-1 also is
      low. No reproductive toxicity has been observed with either rhBMP-2 or OP-1.
      However, there is no human safety data. Subclinical immune responses in human
      subjects to collagen carriers have been reported. Antibody responses to rhBMP-2
      have been detected in less than 1% of spine patients. Low titer immune responses
      have been observed in 38% of patients treated with OP-1. There were no associated
      clinical adverse effects. CONCLUSIONS: Given the available data, both rhBMP-2 and
      OP-1 appear to be safe provided they are used appropriately, placed accurately,
      not allowed to come into contact with decompressed areas, and contained in the
      region of fusion. They must be used with caution in the presence of dural
      defects.

PMID- 12205421
TI  - Purified bovine BMP extract and collagen for spine arthrodesis: preclinical
      safety and efficacy.
AB  - STUDY DESIGN: Rabbit and nonhuman primate posterolateral intertransverse process
      spinal fusions were performed. OBJECTIVES: To determine the preclinical safety
      and efficacy of bBMPx product (a composite of collagen and bovine bone
      morphogenetic protein extract) mixed with demineralized bone matrix for
      posterolateral intertransverse process spinal fusions. SUMMARY OF BACKGROUND
      DATA: A dose response of bovine BMP extract with collagen in demineralized bone
      matrix has demonstrated spinal fusion to a rate of 100% in a rabbit spinal fusion
      model. This study furthers the research to demonstrate safety in the rabbit and
      efficacy of bovine BMP extract for spinal fusion applications in nonhuman
      primates. Additionally, preliminary human clinical data are presented. METHODS:
      For the safety portion of the study, 45 New Zealand white rabbits underwent
      posterolateral intertransverse process spinal fusion after laminectomy. Nine
      additional rabbits served as nontreated control subjects. Graft material
      (autograft or bBMPx product) was placed in the gutters in 30 animals, and no
      material was used in 15 animals. The animals were observed for abnormal physical
      activity, then killed at 8, 29, or 57 days. Histologic evaluation was performed
      on explanted spines. In the nonhuman primate efficacy studies, 54 rhesus macaques
      also underwent bilateral posterolateral intertransverse process fusion. bBMPx
      product with varying bovine BMP extract doses was implanted bilaterally. The
      animals were killed at 4, 8, 12, 18, or 24 weeks. Plain radiograph, computed
      tomography scanning, and histology were performed. RESULTS: The rabbit safety
      study demonstrated that any spinal cord compression or degeneration was caused by
      the inflammatory response after surgery and was equivalent in all groups. These
      issues resolved over time. Efficacy data demonstrated an autograft fusion rate of
      only 21% in the rhesus macaques. The bovine BMP extract demonstrated a dose
      response in which 3 mg per side gave twice the fusion rate as autograft.
      CONCLUSIONS: bBMPx product is safe and effective as an autograft substitute for
      posterolateral intertransverse process spinal fusion. Clinical studies are
      underway.

PMID- 12205422
TI  - Recombinant human osteogenic protein-1 (bone morphogenetic protein-7) as an
      osteoinductive agent in spinal fusion.
AB  - STUDY DESIGN: The data related to spinal applications of osteogenic protein-1
      presented at national meetings or published in peer-reviewed literature are
      reviewed. OBJECTIVES: To review the available data related to the use of
      osteogenic protein-1 for spinal arthrodesis. REVIEW OF BACKGROUND DATA:
      Osteogenic protein-1 (bone morphogenetic protein-7) is a member of the bone
      morphogenetic protein family and has shown strong osteoinductivity in vivo.
      METHODS: The background related to osteogenic protein-1 for spinal applications
      and the known studies presented at national meetings or published in the peer
      reviewed literature are reviewed. RESULTS: Osteogenic protein-1 is able to
      achieve solid bony fusion of the spine in both the anterior and posterolateral
      environments in animal studies and has a good safety profile. Early human trials
      appear to be promising. CONCLUSIONS: Animal studies support the ability of
      osteogenic protein-1 to enhance or replace autograft for spinal arthrodesis in
      both the posterolateral and interbody environment. Human trials ultimately will
      provide data to clarify the optimal role of osteogenic protein-1 in human spinal
      surgery.

PMID- 12205423
TI  - Use of recombinant human bone morphogenetic protein-2 in spinal fusion
      applications.

PMID- 12205425
TI  - Bone morphogenetic protein gene therapy.
AB  - STUDY DESIGN: A retrospective analysis of previous BMP gene therapy and general
      gene therapy publications. OBJECTIVE: To present the potential role of BMP gene
      therapy for the induction of osteogenesis and spinal fusion. SUMMARY OF
      BACKGROUND DATA: A variety of viral and non-viral techniques have been utilized
      to insert foreign transgenes into cells, both in vivo and in vitro. These
      techniques are now being used to transduce cells with a BMP gene to express
      significant amounts of BMP. This secreted BMP can subsequently stimulate
      osteogenesis in a variety of locations, including in the paraspinal regions.
      METHODS: A retrospective analysis of the literature. RESULTS: Direct and ex vivo
      BMP gene therapy has been shown to successfully promote bone healing and
      regeneration in a variety of animal models. Long-term and regulated transgene
      expression are clear advantages of BMP gene delivery, compared to direct BMP
      application. To date, BMP gene delivery with adenoviral vectors have been the
      most effective approach for stimulating bone induction in vivo. CONCLUSIONS:
      Although BMP gene therapy techniques have significant potential for the treatment
      of spine pathology, further preclinical and clinical research and development are
      required before this technology will have direct clinical applications.

PMID- 12205426
TI  - Economic evaluation of bone morphogenetic protein versus autogenous iliac crest
      bone graft in single-level anterior lumbar fusion: an evidence-based modeling
      approach.
AB  - STUDY DESIGN: Economic evaluation provides a framework to explicitly measure and
      compare the value of alternative medical interventions in terms of their
      clinical, health-related quality-of-life, and economic outcomes. Computerized
      economic models can help inform the design of future prospective studies by
      identifying the cost-drivers, the most uncertain parameter estimates, and the
      parameters with the greatest impact on the results and inferences. OBJECTIVE: An
      economic analysis of bone morphogenetic protein versus autogenous iliac crest
      bone graft for single-level anterior lumbar fusion poses several methodologic
      challenges. This article describes how such an economic evaluation may be framed
      and designed, while enumerating challenges, offering some solutions, and
      suggesting an agenda for future research. SUMMARY OF BACKGROUND DATA: An evidence
      based modeling approach can incorporate epidemiologic, clinical, and economic
      data from several sources including randomized clinical trials, peer-reviewed
      literature, and expert opinion. Sensitivity analyses can be conducted by varying
      key parameter estimates within a reasonable range to assess the impact on the
      results and inferences. RESULTS: Preliminary results suggest that from a payer
      perspective, the upfront price of bone morphogenetic protein is likely to be
      entirely offset by reductions in the use of other medical resources. That is,
      bone morphogenetic protein appears to be cost neutral. The cost offsets were
      attributable largely to prevention of pain and complications associated with
      autogenous iliac crest bone graft, as well as reduction of the costs associated
      with fusion failures. CONCLUSIONS: Future research should focus on quantifying
      the health-related quality-of-life impact of bone morphogenetic protein relative
      to autogenous iliac crest bone graft, as well as the impact on lost productivity.

PMID- 12205427
TI  - Influenza prevention 2002-2003.

PMID- 12205428
TI  - Gefitinib (Iressa) for advanced non-small cell lung cancer.

PMID- 12205429
TI  - Tests for drugs of abuse.

PMID- 12205430
TI  - Neotame - a new artificial sweetener.

PMID- 12205431
TI  - Freedom of information.

PMID- 12205432
TI  - Sphingosine 1-phosphate preserves fertility in irradiated female mice without
      propagating genomic damage in offspring.

PMID- 12205433
TI  - An international solution to recruiting physician-scientists?

PMID- 12205434
TI  - Decisions to be made on biologically 'sensitive' research.

PMID- 12205435
TI  - NIH commercializes new imaging technique.

PMID- 12205436
TI  - Trial tests chelation's effect on heart disease.

PMID- 12205437
TI  - Nuclear receptor community goes virtual.

PMID- 12205438
TI  - Atherosclerosis groups bid for fresh funds.

PMID- 12205439
TI  - Resurrecting the resurrection drug.

PMID- 12205440
TI  - Lifestyle drug market booming.

PMID- 12205443
TI  - Endocrine gland-derived VEGF and the emerging hypothesis of organ-specific
      regulation of angiogenesis.
AB  - The diversity in growth and morphological characteristics among endothelial cells
      in different normal tissues and tumors has been long recognized. Yet there has
      been no clear molecular explanation for such diversity at the level of vascular
      endothelial growth factor A (VEGF-A) and other established regulators of
      angiogenesis that are expressed widely and show little tissue selectivity in
      their angiogenic properties. Endocrine gland-derived VEGF represents the first
      example of a tissue-specific angiogenic factor, likely to be followed by others.

PMID- 12205444
TI  - A reevaluation of integrins as regulators of angiogenesis.
AB  - Pharmacological agents directed against the integrins alpha(v)beta(3) and
      alpha(v)beta(5) have been reported to inhibit angiogenesis. However, genetic
      ablations of the genes encoding these integrins fail to block angiogenesis and in
      some cases even enhance it. This apparent paradox suggests the hypotheses that
      these integrins are negative regulators of angiogenesis and that the drugs
      targeting them may be acting as agonists rather than antagonists.

PMID- 12205448
TI  - The makings of a killer.

PMID- 12205450
TI  - 'Good' lipids for asthma.

PMID- 12205449
TI  - Limitations in brain repair.

PMID- 12205451
TI  - Stem cells go for the eyes.

PMID- 12205452
TI  - Keeping telomerase in its place.

PMID- 12205453
TI  - Inflammation takes on Alzheimer disease.

PMID- 12205461
TI  - Natural evolution.

PMID- 12205454
TI  - Paving new pathways.

PMID- 12205462
TI  - Designer meetings.

PMID- 12205463
TI  - The Clonal Selection Theory: what it really is and why modern challenges are
      misplaced.

PMID- 12205464
TI  - Life and death in effector T cells.

PMID- 12205465
TI  - BLySsful interactions between DCs and B cells.

PMID- 12205466
TI  - Does AID need another aid?

PMID- 12205467
TI  - Up the down staircase.

PMID- 12205468
TI  - Transplantation--caught in the crossfire!

PMID- 12205469
TI  - Attacking HIV.

PMID- 12205471
TI  - Growing pains.

PMID- 12205470
TI  - Natural killer cell activation in mice and men: different triggers for similar
      weapons?
AB  - The signaling pathways that regulate B and T lymphocytes are remarkably conserved
      between humans and mice. However, recent evidence suggests that the pathways
      regulating natural killer (NK) cell activation may actually differ between these
      two species. We discuss the controversies in the field and propose that this
      divergence could be deceptive: despite some clear differences between human and
      mouse NK cell receptors, the many ways of activating NK cells and their functions
      may well be conserved.

PMID- 12205472
TI  - Paths to the pancreas.

PMID- 12205473
TI  - ATM heterozygosity and cancer risk.

PMID- 12205474
TI  - Immortalizing the immortal.

PMID- 12205481
TI  - A minor actin catastrophe.

PMID- 12205477
TI  - Genetics, cytokines and human infectious disease: lessons from weakly pathogenic
      mycobacteria and salmonellae.
AB  - Host genetic factors are important in determining the outcome of infections
      caused by intracellular pathogens, including mycobacteria and salmonellae, but
      until now have been poorly characterized. Recently, some individuals with severe
      infections due to otherwise weakly pathogenic mycobacteria (non-tuberculous
      mycobacteria or Mycobacterium bovis bacille Calmette-Guerin) or Salmonella
      species have been shown to be unable to produce or respond to interferon-gamma.
      This inability results from mutations in any of five genes encoding essential
      proteins of the type 1 cytokine cascade: interleukin-12p40, interleukin-12R beta
      1, interferon-gamma R1, interferon-gamma R2 or STAT1. Ten syndromes have thus far
      been identified. Recent insights in genetically controlled host defense and
      susceptibility to mycobacterial disease are discussed.

PMID- 12205482
TI  - Unconventional ways to travel.

PMID- 12205483
TI  - Taking the easy way out?

PMID- 12205484
TI  - TSC1-TSC2: a complex tale of PKB-mediated S6K regulation.

PMID- 12205485
TI  - The progress zone -- alive or dead?

PMID- 12205487
TI  - Changing partners.

PMID- 12205488
TI  - Beating back the bushes.

PMID- 12205489
TI  - Pfizer-Pharmacia merger bodes ill for biotech?

PMID- 12205490
TI  - EMEA approves OGS drug rejected by FDA.

PMID- 12205491
TI  - Efficacy of UK smallpox vaccine questioned.

PMID- 12205492
TI  - US legislation could boost renewable fuel and materials uses.

PMID- 12205493
TI  - New Zealand GMO incident highlights lack of standardized tests.

PMID- 12205494
TI  - US federal agencies add extra steps for handling GM plants.

PMID- 12205496
TI  - Criticism preserves the vitality of science.

PMID- 12205497
TI  - Labeling GM foods--the ethical way forward.

PMID- 12205498
TI  - Just mad about mAbs.

PMID- 12205499
TI  - Beyond gene containment.

PMID- 12205500
TI  - QC in antisense oligo synthesis.

PMID- 12205502
TI  - Sunbaked biotechnology in Australia.

PMID- 12205503
TI  - Reduce, reuse, and recycle.

PMID- 12205504
TI  - Toward a new cash cow.

PMID- 12205505
TI  - Feeding hungry stem cells.

PMID- 12205506
TI  - Creating a good impression.

PMID- 12205507
TI  - Disulfide bond switches.

PMID- 12205508
TI  - Inhibition of glioma growth by tumor-specific activation of double-stranded RNA
      dependent protein kinase PKR.
AB  - Activated double-stranded RNA (dsRNA-dependent protein kinase PKR is a potent
      growth inhibitory protein that is primarily activated in virally infected cells,
      inducing cell death. Here we investigate whether selective activation of PKR can
      be used to kill cancer cells that express mutated genes containing deletions or
      chromosomal translocations. We show that antisense (AS) RNA complementary to
      fragments flanking the deletion or translocation can produce a dsRNA molecule of
      sufficient length to activate PKR and induce cell death following hybridization
      with mutated but not wild-type mRNA. Using the U87MG Delta EGFR cell line, which
      expresses a truncated form of epidermal growth factor receptor (EGFR), Delta(2-7)
      EGFR, we found that expression of a 39-nucleotide (nt) AS RNA complementary to
      the unique exon 1 to 8 junction caused selective death of cells harboring the
      truncated EGFR both in vitro and in vivo but did not affect cells expressing wild
      type EGFR. A lentiviral vector expressing the 39-nt AS sequence strongly
      inhibited glioblastoma growth in mouse brain when injected after tumor cell
      implantation. This PKR-mediated killing strategy may be useful in treating many
      cancers that express a unique RNA species.

PMID- 12205509
TI  - Macrolide-based transgene control in mammalian cells and mice.
AB  - Heterologous mammalian gene regulation systems for adjustable expression of
      multiple transgenes are necessary for advanced human gene therapy and tissue
      engineering, and for sophisticated in vivo gene-function analyses, drug
      discovery, and biopharmaceutical manufacturing. The antibiotic-dependent
      interaction between the repressor (E) and operator (ETR) derived from an
      Escherichia coli erythromycin-resistance regulon was used to design repressible
      (E(OFF)) and inducible (E(ON)) mammalian gene regulation systems (E.REX)
      responsive to clinically licensed macrolide antibiotics (erythromycin,
      clarithromycin, and roxithromycin). The E(OFF) system consists of a chimeric
      erythromycin-dependent transactivator (ET), constructed by fusing the prokaryotic
      repressor E to a eukaryotic transactivation domain that binds and activates
      transcription from ETR-containing synthetic eukaryotic promoters (P(ETR)).
      Addition of macrolide antibiotic results in repression of transgene expression.
      The E(ON) system is based on E binding to artificial ETR-derived operators cloned
      adjacent to constitutive promoters, resulting in repression of transgene
      expression. In the presence of macrolides, gene expression is induced. Control of
      transgene expression in primary cells, cell lines, and microencapsulated human
      cells transplanted into mice was demonstrated using the E.REX (E(OFF) and E(ON))
      systems. The macrolide-responsive E.REX technology was functionally compatible
      with the streptogramin (PIP-regulated and tetracycline (TET-regulated expression
      systems, and therefore may be combined for multiregulated multigene therapeutic
      interventions in mammalian cells and tissues.

PMID- 12205510
TI  - Engineering soluble proteins for structural genomics.
AB  - Structural genomics has the ambitious goal of delivering three-dimensional
      structural information on a genome-wide scale. Yet only a small fraction of
      natural proteins are suitable for structure determination because of bottlenecks
      such as poor expression, aggregation, and misfolding of proteins, and
      difficulties in solubilization and crystallization. We propose to overcome these
      bottlenecks by producing soluble, highly expressed proteins that are derived from
      and closely related to their natural homologs. Here we demonstrate the utility of
      this approach by using a green fluorescent protein (GFP) folding reporter assay
      to evolve an enzymatically active, soluble variant of a hyperthermophilic protein
      that is normally insoluble when expressed in Escherichia coli, and determining
      its structure by X-ray crystallography. Analysis of the structure provides
      insight into the substrate specificity of the enzyme and the improved solubility
      of the variant.

PMID- 12205515
TI  - The role of foreign worker scientists in the US biotechnology industry.

PMID- 12205511
TI  - Licensing research tool patents.

PMID- 12205516
TI  - [Hormone replacement therapy (HRT)].

PMID- 12205517
TI  - [Urogenital diseases in the climacteric: What to do?].

PMID- 12205518
TI  - [When to indicate endovascular treatment in type B aortic dissection?].

PMID- 12205519
TI  - [How to appraise the cervix uteri in obstetrical ultrasonography].

PMID- 12205520
TI  - [Do you indicate surgery based only in genetic examination].

PMID- 12205521
TI  - [What to do in anal idiopathic ulcer in a positive HIV patient].

PMID- 12205522
TI  - [When to indicate and what is the result of open lung biopsy?].

PMID- 12205523
TI  - [Cystatin C: A new marker for children kidney function].

PMID- 12205524
TI  - [Neisseria meningitidis with penicillin intermediate sensitivity: a emergent
      problem].

PMID- 12205526
TI  - [Aneurysmal bone cyst].

PMID- 12205527
TI  - [Stomach neoplasm and inguinal hernia in same patient].

PMID- 12205528
TI  - [Radiotherapy for pancreatic cancer].
AB  - BACKGROUND: The pancreatic adenocarcinoma is an aggressive disease for which cure
      is only possible in less than 20% of the best cases. Adjuvant radiotherapy and
      chemotherapy so far have improved symptoms with little, but significant, increase
      in survival rates. METHODS: Retrospective assessment of 40 patients admitted at
      Department of Radiation Oncology of the Hospital Israelita Albert Einstein
      between April 1993 and August 1999 was done. Radical surgery with tumor resection
      was previously performed in 25 and palliative procedures or nothing in 15.
      RESULTS: Overall actuarial median survival was 14.8 months; and actuarial
      survival rates at 12 and 24 months were 70% and 22.2% respectively. Actuarial
      median survival for the group of patients with resected tumor was 21.4 and for
      the group of patients with non-resected tumor was 16.1 months. Expected survival
      rates at 12 and 24 months were 76% and 32% for the former group and 60% and 0%
      for the latter. CONCLUSIONS: Results were similar to other published series.
      Better drugs and more frequent intraoperative radiotherapy are necessary.

PMID- 12205529
TI  - [To choose who should live: a bioethical study of social criteria to
      microallocation of health care resources in medical emergencies].
AB  - OBJECTIVE: To analyze ethical dilemmas about microallocation of health care
      scarce resources, based on deontological and utilitarian bioethical basis. It
      analyzes some criteria considered in the choices and justifications for patients
      selection in medical emergencies. METHODS: 395 subjects were interviewed in the
      city of Diadema/SP, about dilemmas among two people needing a place in a public
      hospital of emergency service. The presented situations dealed with the following
      social criteria: age, sex, social responsibility and economical condition.
      RESULTS: They pointed that significant portion of those researched seems to
      consider that the use of social criteria is valid and that the people lives can
      have unequal value in situations of scarce resources, accepting social variables
      to prioritize in situations of evidenced medical emergency. CONCLUSIONS: It could
      be evoked the coexistence of deontological orientations, defending the more "weak
      and vulnerable", and utilitarian positions, opting for the potential and life
      expectation as well as for the social responsibility.

PMID- 12205531
TI  - [Sensibility and specificity of cytology and colposcopy exams with the
      histological evaluation of cervical intraepithelial lesions].
AB  - OBJECTIVE: To evaluate the correlation of cytopathological and colposcopycal
      diagnosis with the histopathological analysis from biopsy. METHODS: 80 patients
      from the colposcopy ambulatory of the Hospital e Maternidade Santa Brigida de
      Curitiba, PR, were selected. Those patients were sent to colposcopy under the
      following criteria: 1) previous abnormal cytopathological exams, 2) Indicative
      clinical data or, 3) Suspected lesions on gynecological exam. The statistical
      significance analysis of the results was done using the chi-square test.
      Sensibility, specificity, positive predictive value (PPV) and negative predictive
      value (NPV) were also determined. RESULTS: The patients' mean age was 30.2 (+/
      10.9). Cytopathological capability of identifying lesions was 50% when compared
      to histology. Its specificity was 77%, the sensibility 41%, the PPV 74%, and the
      NPV 45%. Colposcopy capability of identifying lesions was 50%. Its sensibility,
      specificity, PPV and NPV were 96%, 19%, 65% and 75% respectively. The two methods
      associated were capable of identifying 63% of the lesions. CONCLUSIONS:
      Cytopathology was a high specificity exam, while colposcopy from those selected
      patients had a high sensibility. Colposcopy association with cytopathological
      screening, on those selected patients, significantly raises the diagnostic
      accuracy of cervical cancer precursor lesions.

PMID- 12205530
TI  - [Reproductive performance of female wistar rat, descendent of mothers treated
      with levonorgestrel during the lactation].
AB  - Levonorgestrel is one of the contraceptives used by women during lactation.
      Previous studies have shown that the administration of levonorgestrel to
      lactating female rats has affected the offspring, causing puberty delay in males
      and alterations on uterus and oviduct weight. PURPOSE: To study the reproductive
      capacity of F1 females from rats treated with levonorgestrel. METHODS: Female
      Wistar rats were treated with levonorgestrel (0.030 mg/1 ml of distilled water)
      from day 7 to day 13 after birth (day 1 = birth). On day 90 F1 females were mated
      with fertile males and insemination was confirmed by the presence of spermatozoa
      in the vaginal smear (first day of pregnancy). Inseminated females were
      distributed in three groups of 20 animals each (10 F1 control and 10 F1 treated).
      The animals were killed on days 2, 4 and 5 after insemination by ether overdose
      inhalation and the ovaries, oviducts and uterine cornua were removed. The ovaries
      were weighed and the corpora lutea counted. Oviducts and corpora lutea were
      washed with saline solution and the pre-embryos were counted and examined in all
      segments. RESULTS: The ovaries weight, the number of corpora lutea, the number
      and development phase of the pre-embryos were similar in both groups. CONCLUSION:
      In the experimental model used, F1 females whose mothers were treated with
      levonorgestrel during lactation, did not show any alteration in their
      reproductive capacity.

PMID- 12205532
TI  - [Linear growth evaluation of asthmatic children].
AB  - OBJECTIVE: The aim was to assess the effect of atopic asthma on the stature and
      growth velocity of Brazilian adolescents and children, taking into consideration
      their socioeconomic conditions, natural disease history and individual growth.
      METHODS: 66 patients had been seen at the Pneumology, Immunology and Allergy
      Ambulatory, Unicamp, University Hospital. Their height and weight were measured
      every 3 months and the bone age was obtained once during this period. The
      patients were divided into two groups according to their puberal development:
      prepubertal and puberal. RESULTS: Prepuberal - 40 patients with 0.6 to 1.5 years
      (1.04+/-0.19) of follow-up. The mean height/age z-score was 0.028 +/- 0.978 and
      the mean growth velocity z-score was 0.045 +/- 1.11. Puberal - 26 patients with
      0.5 to 1.3 years (0.99+/-1.722) of follow-up. The mean height/age z-score was
      0.170 +/- 1.209 and the mean growth velocity z-score was 0.042 +/- 2.321. In the
      prepuberal group the patients who had one or more pneumonia during the follow-up
      had lower mean growth velocity z-score than the others (p=0.04). The high dose of
      glucocorticoids used by puberal patients was considered a risk factor for growth
      velocity (p=0.02). CONCLUSIONS: The children and adolescents suffering from
      asthma could grow normally and attain their full genetic potential by treating
      the disease correctly, controlling infections and having favorable living
      conditions.

PMID- 12205533
TI  - [Profile of patients with diabetes type 1: insulinotherapy and self-monitoring].
AB  - OBJECTIVES: A study carried out in Londrina - PR, with the cohort of local
      patients from Brazilian Study on the incidence of Diabetes Mellitus Type 1
      (EDID). To know the insulin treatment and the plan for glycemic self-monitoring
      used by these patients; to verify their knowledge as for what they consider the
      optimization of these parameters and limitations of use. METHODS: A survey was
      conducted with objective questions to 63 patients of the cohort. RESULTS: The
      average age was 13 years, without gender predominance. It was verified that most
      of the patients, 79.36%, (n=50) took at least 2 daily applications of insulin.
      All of them used insulin NPH in one (n=13) or two (n=50) doses. The use of
      regular insulin, in variable programs, was associated to the NPH in 41.27% (n=26)
      of the patients (The most frequent insulin type used was human 53.97% (n=34). Of
      the patients not making use of human insulin, 44.83% (n=13) considered it of high
      cost and 95.24% (n=60) would make use of it if it was distributed by the
      Government Unified Health System. As for the monitoring, 63.40% (n=40) took the
      tests up to 7 times a week, 20.63% (n=13) from 15 to 21 and only 1 patient from
      29 to 35 tests. The high cost was the reason for 48.21% (n=27) not to take the
      tests; 58.73% (n=37) would take the test in the blood and 33.33% (n=21) either in
      the blood or in the urine if they were given the reactive ribbons. CONCLUSION: In
      this cohort of patients, although the human insulin is already adopted as the use
      of choice, the outline insulin treatment plan is still traditional and the
      monitoring is far behind the ideal.

PMID- 12205534
TI  - [Cost involved in retrieving multiple organs].
AB  - The process of organ donation and retreat is complex and involves a high cost for
      hospitals that do it. PURPOSE: to survey the expenses with the process of
      donation and retreat of organs. METHODS: retrospective study based on medical
      records of 32 donors, admitted in the Search Organs Organisation do Instituto
      Dante Pazzanese de Cardiologia, during the period from January to December of
      1999. RESULTS: the process is complex and involves a special structure as well as
      24 hours of activities, making it costly. Expenses were related with the
      following items: human resources, permanent material, public utilities,
      complementary examinations, depreciation of equipment and transportation. A
      comparison with the values reimbursed by the Single Health System (SUS) followed.
      CONCLUSION: the total cost was high than the reimbursement provided by SUS,
      showing the necessity of research about cost of procedures and the reinvestment
      margin.

PMID- 12205535
TI  - [Safety measures in traffic and hospital morbimortality in craniocerebral trauma
      in the Distrito Federal].
AB  - BACKGROUND: The study analyzed the effectiveness of safety measures (seat belt,
      velocity control) in traffic. The parameters were the decrease in number and
      severity in head injury trauma (HIT). METHODS: Epidemiological study, based on
      the evaluation of secondary data about head injury. The data were analyzed
      between two periods, before (1992) and after (1997) measures implementation.
      RESULTS: We compared the indices (per 100.000 population) of victims in the two
      periods. In 1992 there were 125.5 victims, and in 1997 there were 155.8. From
      this total in group 1 we had 26.2 cases of HIT with 5.2 deaths, in 1997 we had
      62.1 with 4.1 deaths. About severity: in the first period were 9.6 cases severe
      or moderate head injury, in group 2 there were 8.1 cases. CONCLUSIONS: There was
      an increase in the number of victims of HIT caused by automobile accidents in
      this period, however the severity of the trauma showed a small decrease, possibly
      security measures were not efficiently in reducing the number of cases but may
      have been successful in reducing deaths related to this accidents.

PMID- 12205536
TI  - [Influence of hypertension on the incidence of end-stage renal disease in negroes
      and mulattoes with glomerulonephritis].
AB  - OBJECTIVE: To assess whether hypertension diagnosed during the first two months
      of follow-up is associated with the incidence of end-stage renal disease (ESRD)
      in negroes and mulattoes with glomerulonephritis after taking into account age,
      gender and the histological diagnosis. METHODS: A retrospective cohort study
      based on a sample of' 120 negro and mulatto patients with glomerulonephritis, 26
      with membranoproliferative glomerulonephritis (MPGN), 58 with focal segmental
      glomerulosclerosis (FSG) and 36 with other types of glomerulonephritis (OTGN).
      Hypertension was considered present if antihypertensive treatment was used, in
      adults (age >18 years) with a mean of the three first systolic blood pressures of
      140 mmHg or a mean of the corresponding diastolic blood pressure of 90 mm Hg or
      greater. For ages equal to or below 18 years the criteria recommended by the
      "Task Force on Blood Pressure in Children" were used. RESULTS: Hypertension was
      diagnosed in 48 of the 120 patients (41.6%). The incidence of ESRD was
      approximately 2.6 times higher in hypertensive patients (relative risk(RR)=2.62;
      95 % confidence interval (CI) =1.01-7.03, p=0.031). This association between
      hypertension and higher risk of ESRD was similar between the group younger than
      19 and the group older than 18 years. Even after adjusting for age, gender and
      histologic type, the incidence of ESRD remained higher (and marginally
      significant) in the hypertensive than in the normotensive group (adjusted
      RR=2.15; IC 95%=0.86-5.39, p=0.07). CONCLUSIONS: According to the findings, early
      detection of hypertension in negroes and mulattoes with glomerulonephritis helps
      to identify patients with higher risk of ESRD, independently of age, gender and
      histologic type. Further research is needed to determine to what extent the
      severity of hypertension and the degree of blood pressure control contribute to
      the development of ESRD in negroes and mulattoes with glomerulonephritis.

PMID- 12205537
TI  - [Civil, criminal and ethical liability of medical doctors].
AB  - In the last years doctors have been the target of a growing number of civil,
      criminal law suits, as well as ethical procedures. Medicine is a widely targeted
      career, not only owing to its inherent risks, but also owing to a mistaken
      approach of the Judiciary Power about the obligations of medical doctors.
      Decisions of the Medical Board in ethical procedures have an impact in civil and
      criminal justice and therefore should be followed closely. The purpose of this
      review is to provide a wide view from a doctor-lawyer perspective of cases
      involving civil, criminal liability of anesthesiologists as well as ethical
      procedures against them, in an effort to make them comprehensible to doctors.
      After a brief historical introduction civil liability foundations and legal
      articles are examined. Responsibilities of doctors, hospitals and health
      insurance providers are discussed separately, as well as reparation mechanisms.
      Crimes possible to occur during medical practice and respective penalties are
      described; the direct relationship between crime and civil reparation is
      demonstrated. The administrative nature of ethical procedure is described,
      emphasizing that the legal character of its penalties often serve as grounds for
      civil and criminal justice decisions. Prevention is still the best medicine. Good
      medical practice and a good medical-patient relationship are still the best ways
      to minimize lawsuits and their repercussions. Doctors should have some knowledge
      of juridical mechanisms in lawsuits and ethical procedures, but should not take
      defense initiatives without prior consultation of an attorney. Civil, criminal
      and ethical liability of physicians.

PMID- 12205546
TI  - Local recurrence following total mesorectal excision with double-stapling
      anastomosis for rectal cancers: analysis of risk factors.
AB  - This study reviewed the local recurrence rate in patients who had undergone total
      mesorectal excision and double-stapling low anterior resection for mid and distal
      rectal cancers. It also aimed to identify risk factors for local recurrence
      through univariate and multivariate analyses. Consecutive patients with rectal
      cancers within 12 cm of the anal verge treated with total mesorectal excision and
      double-stapling low anterior resection from August 1993 to December 2000 were
      studied. The demographic data, operative details, tumor characteristics, and
      follow-up data were collected prospectively. Factors that might affect the local
      recurrence rate were analyzed with univariate and multivariate analyses. A total
      of 270 patients were included in the study (156 men, 114 women). The mean +/- SD
      age was 64.83 +/- 11.27 years. The mean +/- SD level of the tumor was 7.17 +/-
      1.90 cm. All anastomoses were performed within 5 cm of the anal verge. During the
      mean follow-up of 35.5 months, 12 patients developed local recurrence. The 5-year
      actuarial local recurrence rate was 7.3%. The presence of lymphovascular invasion
      and the resection margin of < or = 1 cm were found to be risk factors for local
      recurrence in the univariate analysis. In the multivariate analysis, the presence
      of lymphovascular invasion was the only independent factor for local recurrence.
      In the group of patients with lymphovascular invasion, proximal tumors (6-12 cm
      from the anal verge) were shown to have a significantly lower local recurrence
      than those within 6.1 cm from the anal verge (4.2% vs. 37.8%; p <0.001). Low
      anterior resection performed with double stapling and total mesorectal excision
      achieved a local recurrence rate of 7.3%. The presence of lymphovascular invasion
      was the only independent risk factor for local recurrence. A high local
      recurrence rate was associated with distal cancers (? 6 cm from the anal verge)
      with lymphovascular invasion. Adjuvant therapy for local control should be
      considered for this subgroup of patients.

PMID- 12205547
TI  - Hemodynamic effect of transdermal glyceryl trinitrate on newly constructed
      arteriovenous fistula.
AB  - Transdermal glyceryl trinitrate (GTN) administration may have a beneficial effect
      in the creation of an arteriovenous fistula (AVF) by increasing blood flow
      through the access and by inhibiting platelet aggregation. We evaluated the
      hemodynamic effects of transdermal GTN administration on newly constructed
      arteriovenous fistula. Radiocephalic fistula at the wrist (Brescia fistula) was
      constructed as the initial vascular access in 31 uremia patients (study = 16,
      control = 15). The patient demographics and the etiology of chronic renal disease
      were similar in the two groups. None of the patients had severe vasculitis. The
      mean duration of chronic renal disease was 8 months (1-24 months). The diameter,
      blood flow rate, and blood output at the drainage vein and the subclavian vein
      were measured by duplex ultrasonography 24 hours after the procedure. The
      measurements were performed again with transdermal GTN (10 mg/24 hours adhesive
      patch) administration in the study group and, without any medication, in the
      control group 4 hours after the initial measurements were taken. In the study
      group, all of the hemodynamic parameters were significantly increased over the
      initial measurements (p <0.05) whereas in the control group all hemodynamic
      parameters were unchanged, except the diameter of the subclavian vein (p <0.05).
      The actual change in hemodynamic parameters was significant in the study group
      when compared to the control group (p <0.05). Our data showed that transdermal
      GTN administration at the forearm increases flow through the Brescia fistula.

PMID- 12205548
TI  - Surgical strategy in a kindred with a rare RET protooncogene mutation of variable
      penetrance with regard to multiple endocrine neoplasia.
AB  - Prophylactic thyroidectomy is recommended for carriers of RET protooncogene
      mutations owing to their nearly complete penetrance for medullary thyroid
      carcinoma (MTC). However, this guideline is challenged by mutations exhibiting
      variable penetrance of C-cell pathology. A 38-year-old woman presented with
      pathologic basal and pentagastrin-stimulated calcitonin levels. Genetic analysis
      revealed a heterozygous RET protooncogene germline mutation in codon 791 (exon
      13) (TAT(Tyr)-->TTT(Phe)), followed by thyroidectomy and systematic central lymph
      node dissection. Histology showed C-cell hyperplasia (CCH) only. Three additional
      carriers were identified among family members. The 71-year-old father refused
      surgery despite pathologic calcitonin levels. The index patient's 37-year-old
      sister had normal basal and stimulated calcitonin levels, and her 6-year-old son
      had a 10-fold rise of calcitonin after pentagastrin stimulation. Both patients
      underwent the same operation as the index patient. The sister had 25 hyperplastic
      C-cells, but the her son had extensive CCH without MTC. The eldest uncle of the
      index patient had died of metastatic MTC at the age of 52 with unknown carrier
      status. Despite variable penetrance, each carrier of a RET protooncogene germline
      mutation should undergo thyroidectomy, even if basal and stimulated calcitonin
      levels are normal because at present no test can exclude or predict the age of
      development of MTC. Moreover, pathologic calcitonin levels cannot differentiate
      between CCH and MTC. Central lymph node dissection is recommended, as lymph node
      metastases occur early, significantly worsening the prognosis.

PMID- 12205549
TI  - Intravenous calcium injection test is a novel complementary procedure in
      differential diagnosis for gastrinoma.
AB  - The current study evaluated efficacy of the intravenous calcium injection test as
      a new diagnostic approach to clarify the existence of gastrinoma, which often
      goes undetected with routine testing. Twenty-six patients with hypergastrinemia
      were studied. For the calcium injection test, blood samples were taken from 12
      patients with hypergastrinemia (HG), and three healthy volunteers, and one
      patient with nonfunctioning endocrine tumor in the pancreas (control). We
      compared results of the calcium injection test with those of the secretin test
      and the selective arterial secretagogue injection (SASI) test. The SASI test with
      secretin was performed in 24 of 26 patients with hypergastrinemia, including 22
      of 24 patients with Zollinger-Ellison syndrome (ZES). Accuracy in the diagnosis
      of tumor localization by the SASI test was 95% (21 of 22) in ZES patients. The
      secretin test was negative in 3 of 21 patients with ZES (14%). Either the
      secretin test or the SASI test was positive in 22 of 23 patients (96%). The
      calcium injection test was administered to 12 patients in the HG group and 4
      controls. The HG group showed significantly higher serum gastrin levels than
      those of the control group in the calcium injection test. Eight of 10 ZES
      patients (80%) had a positive calcium injection test. We could diagnose
      gastrinomas in 100% of ZES patients by either the calcium injection test or the
      secretin test. We have thus confirmed the efficacy of the intravenous calcium
      injection test in the diagnosis of gastrinoma. The calcium injection test could
      become an adjunct in the diagnosis of gastrinoma, which often goes undetected
      with routine testing.

PMID- 12205550
TI  - Assessment of early brain damage in carotid endarterectomy: evaluation of S-100B
      serum levels and somatosensory evoked potentials in a pilot study.
AB  - The release of the neuronal protein S-100B into the circulation has been
      suggested as an early indication of cellular brain damage. The objective of this
      prospective pilot study was to determine S-100B serum levels in patients
      undergoing cross-clamping during carotid endarterectomy (CEA) and to correlate
      the results with the monitoring of somatosensory evoked potentials (SSEP) and the
      neurological short-term outcome. Arterial blood samples of 21 patients were drawn
      before oral intubation, cross-clamping, and unclamping, as well as before
      extubation and 6 hours later. Recording of SSEP was obtained during carotid
      occlusion and reperfusion. If loss of SSEP appeared, cerebral ischemia was
      assumed and an intraluminal shunt was placed. During cross-clamping, S-100B serum
      levels of 14 patients increased significantly from 0.05 ng/ml to 0.21 ng/ml, but
      returned to baseline levels after unclamping. In 5 cases, loss of SSEP amplitudes
      occurred but was reversed by the shunt insertion. No significant differences of S
      100B serum values, neurological examination, and carotid duplex surveillance
      became obvious in this group when compared to the patients with undisturbed SSEP.
      However, 2 patients with complete disappearance of postcentral SSEP components
      suffered from neurological deficits in the postoperative period. S-100B serum
      levels remained highly elevated 6 hours after extubation (0.78 ng/ml and 0.41
      ng/ml) compared to the baseline values (0.15 ng/ml and 0.07 ng/ml). During CEA a
      transitory increase of the S-100B serum levels appears to present an impairment
      of the blood-brain barrier integrity without any neurological deficits. In
      contrast, persistently elevated S-100B serum levels seem to be associated with
      transient loss of SSEP and development of neurological deficits.

PMID- 12205551
TI  - History of the ISS/SIC: Robert Danis, a true general surgeon.
AB  - Robert Danis created his Prize in 1947 to reward a surgeon-member of the Societe
      Internationale de Chirurgie (presently ISS-SIC), "author of the most important
      and personal work in connection with surgical treatment of fractures."
      Consequently, many people believe that Robert Danis was an orthopedic surgeon. In
      fact, he was a man interested in all fields of surgical activity, not only in
      bone and joint surgery.

PMID- 12205552
TI  - Beneficial effect of deletion variant of hepatocyte growth factor for impaired
      hepatic regeneration in the ischemically damaged liver.
AB  - This study was conducted to determine the influence of hepatic ischemia and
      reperfusion (HIR) injury on liver regeneration and the effect of the deletion
      variant of hepatocyte growth factor (dHGF) under these conditions. Male Sprague
      Dawley rats were subjected to 60 minutes of total hepatic ischemia, and two
      thirds hepatectomy was performed just before reperfusion. Animals received
      intravenous administration of either vehicle buffer (vehicle control group) or
      dHGF (1 mg/kg) (HGF group) at the end of the period of hepatic ischemia and again
      6 hours after reperfusion. At 8 hours after hepatectomy, plasma HGF levels in the
      vehicle control group were significantly lower than those in the nonischemic
      controls. Plasma aspartate transaminase levels in the vehicle control group
      reached 3,462 +/- 1,039 IU/L, but levels in the HGF group were significantly
      inhibited to 1,849 +/- 605 IU/L. The relative liver weight in the vehicle control
      group was significantly greater than in the HGF group, a finding that was
      implicated in focal liver necrosis with sinusoidal congestion. Less histological
      damage was observed in the HGF group. Twenty-four hours after hepatectomy, an
      increase in the relative liver weight in nonischemic controls and in the HGF
      group was higher than that in vehicle control group, and the 5-bromo
      2?deoxyuridine (BrdU) labeling index in the HGF group was 23% versus 18% in the
      nonischemic controls. Administration of dHGF significantly improved the 7-day
      survival to 82% versus 40% in the vehicle control group. dHGF has potential
      benefit as a pharmacological agent to ameliorate impairment of the hepatic
      microcirculation and to potentiate a regeneration response in the ischemically
      damaged liver after hepatectomy and/or liver transplantation.

PMID- 12205553
TI  - Spigelian hernias: repair and outcome for 81 patients.
AB  - Spigelian hernia is a rare partial abdominal wall defect. The frequent lack of
      physical findings along with vague associated abdominal complaints makes the
      diagnosis elusive. A retrospective review of Mayo Clinic patients was performed
      to find all patients who had undergone surgical repair of a Spigelian hernia from
      1976 to 1997. Patients were scrutinized for presentation, work-up, therapy, and
      outcome. The goal of this study was to obtain long-term outcome. The study was
      set in a tertiary referral center. There were 76 patients in whom 81 Spigelian
      hernias were repaired. Symptoms most commonly included an intermittent mass (n =
      29), pain (n = 20), pain with a mass (n = 22), and bowel obstruction (n = 5).
      Five patients were asymptomatic. Preoperative imaging was performed in 21
      patients and correctly diagnosed the hernia in 15. Spigelian hernias were
      repaired by primary suture closure (n = 75), mesh (n = 5), and laparoscopic (n =
      1) techniques. Eight patients (10%) required emergent operations. Thirteen
      hernias (17%) were found to be incarcerated at the time of the operation. Overall
      mean follow-up for the 76 patients was 8 years, with three hernia recurrences
      identified. Spigelian hernia is rare and requires a high index of suspicion given
      the lack of consistent symptoms and signs. An astute physician may couple a
      proper history and physical examination with preoperative imaging to secure the
      diagnosis. Mesh and laparoscopic repairs are viable alternatives to the durable
      results of standard primary closure. Given the high rate of
      incarceration/strangulation, the diagnosis of Spigelian hernia is an indication
      for surgical repair.

PMID- 12205554
TI  - Grey Turner Memorial Lecture. Progress in gastrointestinal cancer management:
      challenges of the twenty-first century.

PMID- 12205555
TI  - Collis-Nissen procedure in patients with esophageal atresia: long-term
      evaluation.
AB  - A subset of patients with esophageal atresia (EA) have an associated short
      esophagus and require an antireflux procedure. The Collis-Nissen procedure, which
      consists of a combination of Collis gastroplasty and Nissen fundoplication, is
      considered an option in such conditions. The long-term results of EA patients
      undergoing this procedure have rarely been reported. The results of the Collis
      Nissen procedure were examined in four EA patients with follow-up for an average
      of 9 years. The Collis-Nissen procedure was conducted concurrently with segmental
      esophageal resection for an associated congenital esophageal stenosis close to
      the esophagogastric junction in two postoperative Gross type C patients (7
      months, 2 years), as an antireflux operation in a postoperative Gross type A
      patient with an unreducible sliding hiatal hernia (10 years), and with primary
      repair of EA in a Gross type A patient with a long gap (4 months). There were no
      significant complications except minor anastomotic leakage and an anastomotic
      stenosis that required postoperative dilation. Significant reflux was negative,
      as shown by an upper gastrointestinal study and scintigraphy. Limited esophagitis
      just above the esophagogastric junction was observed in a Gross type A patient
      with a long mediastinal gastric segment. Swallow-related pressure reduction at
      the wrapping cuff was detected by manometric examination. The Collis-Nissen
      procedure is a useful option for treating EA patients who require esophageal
      lengthening and control of gastroesophageal reflux.

PMID- 12205557
TI  - Videolaparoscopic resection of insulinomas: experience in two institutions.
AB  - Laparoscopic resection of islet cell tumors has been performed in some selected
      cases. The aim of the study was to analyze the experience of two institutions in
      the laparoscopic management of insulinomas. In a 4-year period, videolaparoscopic
      resection of sporadic insulinomas was performed in 9 patients. All patients had
      hypoglycemia/hyperinsulinism and a solitary tumor demonstrated by image studies.
      Demographics, surgical findings, results, and complications were analyzed. Mean
      age of the patients was 43 years. One patient was male and eight were females.
      One tumor was located in the head of the pancreas, 4 in the body, and 4 in the
      tail. Laparoscopic resection was completed in all patients. Procedures included 4
      enucleations and 5 distal pancreatectomies. Pancreatic resection with splenic
      preservation was achieved in 4 cases. Intraoperative ultrasound was used in 7
      patients. Mean size of the tumors was 1.6 cm. All patients became normoglycemic
      after surgery. Complications included one pancreatic fistula, one pleural
      effusion, and one peripancreatic fluid collection. All resolved spontaneously. In
      a follow-up period between 3 and 48 months no evidence of recurrence has been
      observed. This series supports laparoscopic resection of preoperatively localized
      benign solitary insulinomas. The operation provides the advantages of minimally
      invasive surgery and can be safely performed in most cases.

PMID- 12205558
TI  - Pancreaticoduodenectomy for islet cell tumors of the head of the pancreas: long
      term survival analysis.
AB  - Pancreaticoduodenectomy (PD) has been performed infrequently for islet cell
      tumors of the pancreas because of the perceived perioperative morbidity and the
      relatively protracted natural history of those tumors. To determine whether the
      improved safety of PD affects long-term outcome of patients with islet cell
      tumors, we reviewed our experience. All consecutive patients who underwent PD or
      total pancreatectomy for islet cell tumors between 1980 and 1995 were analyzed.
      Diagnoses were based on histologic findings and endocrine (biochemical)
      manifestations of the tumors. Patients were followed by outpatient clinic visits
      and mail correspondence. Clinical and pathologic factors were analyzed for
      prognostic risk. Survival and recurrence curves were generated using the Kaplan
      Meier method, and the log-rank test was used for comparison (p <0.05 was
      significant). We identified 29 patients who fulfilled the inclusion criteria with
      an even distribution by gender (14M:15F). Mean age of patients was 56 years (SD
      +/- 14 years); mean tumor size was 4.4 cm (SD +/- 2.6 cm). Most tumors were
      nonfunctioning (n = 20); there were 4 somatostatinomas, 3 insulinomas, and 2
      gastrinomas. Operating time was 316 minutes (SD +/- 75 minutes), median
      transfusion requirement was 0 units (mean 1.5 units). Standard Whipple resection
      was performed in 20 patients; the pylorus-preserving Whipple procedure, in 7; and
      total pancreatectomy, in 2. Regional lymph nodes were involved by tumor in 16
      patients. The complication rate was 31%, and operative mortality was 10% (n = 3).
      Length of hospital stay was 17 days (SD +/- 8.8 days). Overall survival was 81%
      and 70% at 5 and 10 years. Recurrence-free survival was 76% at 5 and 10 years.
      There was a trend toward greater recurrence-free survival for node-negative
      patients (88% vs 65% at 5 years, p = 0.13), and overall survival was greater for
      node-negative patients (100% vs 67% at 5 years, p = 0.04). Mean follow-up was 8.8
      years. PD is an appropriate strategy for selected malignant islet cell tumors of
      the pancreas, which offers extended survival with a low recurrence rate and
      control of endocrine symptoms.

PMID- 12205559
TI  - Reoperation for renal hyperparathyroidism.
AB  - Reoperation for secondary hyperparathyroidism (HPT) due to uremia (2HPT) may be
      required among patients with persistent renal failure if not all parathyroid
      glands are removed at the initial operation. Between March 1981 and July 2001,
      altogether 1,110 patients underwent total parathyroidectomy with forearm
      autograft for advanced 2HPT in our department. In this study, we evaluated the
      clinical features of patients who required reoperation and classified them into
      persistent HPT [the lowest intact parathyroid (PTH) level after initial operation
      remained higher than 60 pg/ml] and recurrent HPT (the lowest intact PTH level was
      normalized after surgery but reelevated became high enough to require
      reoperation). Removal of residual glands was indicated in 30 (2.7%) cases for
      persistent or recurrent HPT. All remaining glands were detected by preoperative
      imaging diagnoses. In 44 (4.0%) patients persistent HPT was recognized and in 15
      of them (1.4% of all cases) reoperation was required. In 11 cases, the
      responsible glands were supernumerary ones removed from the mediastinum. In 4
      cases, the glands were resected from the neck. In 15 cases (1.4%), reoperation
      was performed for recurrent HPT when residual glands were left either in the neck
      or in the thymic tongue. In all but one case, the missed glands were
      supernumerary. This study reveals that it is often difficult to avoid persistent
      HPT induced by mediastinal supernumerary glands and recurrent HPT caused by small
      glands left in the neck. Our findings indicate that patients with uremia should
      be closely followed considering the possibility that persistent or recurrent HPT
      may occur after parathyroidectomy.

PMID- 12205560
TI  - Locally applied granulocyte-macrophage colony-stimulating factor improves the
      impaired bowel anastomoses in rats with long-term corticosteroid treatment.
AB  - Inflammation is an essential component of the first phase of anastomotic wound
      healing, and it is suppressed by corticosteroids. The anti-inflammatory effect of
      corticosteroids is largely responsible for the impairment of wound healing in
      bowel anastomosis. It has been reported that local application of granulocyte
      macrophage colony-stimulating factor (GM-CSF) improves the healing process in
      dermal wounds. In the present study, we investigated the effects of locally
      injected GM-CSF on anastomotic wound healing in long-term corticosteroid treated
      rats. Eighty male Sprague-Dawley rats were randomized into four groups. (1)
      control, (2) steroid, (3) steroid + local GM-CSF, (4) steroid + systemic GM-CSF.
      In groups 2, 3, and 4, methylprednisolone (5 mg/kg) was injected IM daily for 14
      days. After 14 days, following anesthesia and laparotomy, colonic anastomosis was
      performed 3 cm away from the peritoneal reflection. In group 3, 50 mg GM-CSF was
      injected into the perianastomotic area. In group 4, 50 mg GM-CSF was applied
      subcutaneously. On postoperative day 3, repeat laparotomies were performed and
      bursting pressures, hydroxyproline levels, and histopathology examinations were
      studied. The mean values of bursting pressures and hydroxyproline levels in group
      3, treated with steroid + local GM-CSF, were significantly higher than that of
      the group 2 and group 4 values. In the histopathology examination, the mean score
      of group 3 was significantly higher than that of groups 2 and 4. Our study
      indicates that local application of GM-CSF significantly improves the impaired
      anastomotic wound healing in rats treated with long-term corticosteroid.

PMID- 12205561
TI  - Modified technique of percutaneous dilational tracheostomy in 600 cases.
AB  - Tracheostomy is frequently required for the treatment of critically ill patients
      to prevent the complications with prolonged translaryngeal intubation. It may
      facilitate airway suctioning and improve patient comfort during the process of
      weaning. The purpose of the study was to introduce a new modified technique for
      percutaneous dilational tracheostomy (MPDT) and assess its advantages. From
      November 1997 through December 2000, a series of 600 patients (350 men, 250
      women; mean age 44.5 years) underwent MPDT in our department. The technique we
      used is a combination of the Seldinger and Schachner techniques with an incision
      of 2 to 3 cm between the cricoid cartilage and the notch. Using a small automatic
      retractor, the thyroid muscles were dissected with the help of a curved mosquito
      clamp. This gave us the opportunity to control the isthmus and offered the
      possibility of ligation when the thyroid was large, providing a good operative
      field directly on the trachea. Hence we avoided traumatizing the isthmus, which
      is the main source of hemorrhage during this procedure. The mean operating time
      was 4.5 minutes. The morbidity rate was 0.04%. One patient developed a
      subcutaneous emphysema and in three cases we had to ligate the external jugular
      vein. The surgical incision was completely healed within 3 to 4 days after
      removing the tracheostoma. No tracheal stenoses were observed during the follow
      up. MPDT is a safe, applicable technique that can be performed quickly even by a
      nonsurgeon in the intensive care unit and emergency department, with a low risk
      of complications because there is a direct view of the trachea and minimal
      trauma.

PMID- 12205562
TI  - History of the ISS/SIC: Antoine Depage, one of the founders of the ISS/SIC.
AB  - Antoine Depage, born near Brussels in 1862, was one of the founders and first
      Secretary General of the Societe Internationale de Chirurgie (ISS-SIC). After an
      excellent medical education at the Free Brussels University, he became professor
      at the same university at the age of 27. Surgically trained by Prof. Thiriar, he
      became one of the leading Belgian surgeons at the end of the nineteenth century,
      and he published more than 100 articles in national and international journals.
      In 1907 he founded a school for nurses in Brussels, to be directed by Edith
      Cavell. He also vigorously transformed the organization of the public hospitals
      in the Belgian capital. During World War I Queen Elisabeth appointed him surgeon
      in-chief of the Ocean-hospital in De Panne, where more than 50,000 soldiers with
      wounds, fractures, cerebral trauma, nitrous gas intoxication, and infectious
      diseases, among other problems were treated. The results he and his team obtained
      were excellent, and mortality was low. Many surgeons, including Alexis Carrel, as
      well as distinguished political leaders came to visit him in the hospital
      barracks. After the war he was honored by many political and scientific
      organizations, including the Societe Internationale de Chirurgie. He served our
      Society not only as Secretary General from 1902 to 1912 but became President of
      the 4th Congress of the ISS-SIC in New York. Antoine Depage died after a long
      illness in 1925.

PMID- 12205563
TI  - A gene mutated in nephronophthisis and retinitis pigmentosa encodes a novel
      protein, nephroretinin, conserved in evolution.
AB  - Nephronophthisis (NPHP) comprises a group of autosomal recessive cystic kidney
      diseases, which constitute the most frequent genetic cause for end-stage renal
      failure in children and young adults. The most prominent histologic feature of
      NPHP consists of development of renal fibrosis, which, in chronic renal failure
      of any origin, represents the pathogenic event correlated most strongly to loss
      of renal function. Four gene loci for NPHP have been mapped to chromosomes 2q13
      (NPHP1), 9q22 (NPHP2), 3q22 (NPHP3), and 1p36 (NPHP4). At all four loci, linkage
      has also been demonstrated in families with the association of NPHP and retinitis
      pigmentosa, known as "Senior-Loken syndrome" (SLS). Identification of the gene
      for NPHP type 1 had revealed nephrocystin as a novel docking protein, providing
      new insights into mechanisms of cell-cell and cell-matrix signaling. We here
      report identification of the gene (NPHP4) causing NPHP type 4, by use of high
      resolution haplotype analysis and by demonstration of nine likely loss-of
      function mutations in six affected families. NPHP4 encodes a novel protein,
      nephroretinin, that is conserved in evolution--for example, in the nematode
      Caenorhabditis elegans. In addition, we demonstrate two loss-of-function
      mutations of NPHP4 in patients from two families with SLS. Thus, we have
      identified a novel gene with critical roles in renal tissue architecture and
      ophthalmic function.

PMID- 12205565
TI  - Bone marrow stem cells do not repopulate the healthy upper respiratory tract.
AB  - Recent studies reported differentiation of both bone marrow and tissue-specific
      stem cells into cells of other organs. The demonstration that bone marrow stem
      cells differentiate into human hepatocytes in vivo has raised the possibility of
      new therapeutic approaches for liver disease. For diseases such as cystic
      fibrosis (CF), correction of the respiratory epithelium is being attempted by
      gene therapy. Differentiation of bone marrow stem cells into epithelium of the
      lung and airway was recently reported in an animal model, and would provide an
      alternative approach. We examined the nasal epithelium of female patients up to
      15 years after gender-mismatched bone marrow transplantation. Donor-derived
      epithelial cells were sought with a combination of Y-chromosome fluorescence in
      situ hybridization and anti-cytokeratin antibody. In nasal brushing samples from
      6 transplant-recipients, a median of 2.5% (range, 0.7-18.1%) of nuclei was male
      and identified as being of donor-origin. However, a complete absence of staining
      with anti-cytokeratin antibodies confirmed that these were not epithelial cells,
      but were likely to be either intraepithelial lymphocytes or mesenchymal cells.
      Following whole bone marrow transplantation, bone marrow progenitor cells do not
      differentiate into respiratory epithelium of the healthy upper airway. The
      differences between this and other studies could relate to the cells
      transplanted, to differential rates of turnover, or to the requirement for
      specific triggers to stimulate migration and differentiation. In the absence of
      such conditions, whole bone marrow transplantation is unlikely to provide a route
      for correction of the CF airway.

PMID- 12205564
TI  - Human diallelic insertion/deletion polymorphisms.
AB  - We report the identification and characterization of 2,000 human diallelic
      insertion/deletion polymorphisms (indels) distributed throughout the human
      genome. Candidate indels were identified by comparison of overlapping genomic or
      cDNA sequences. Average confirmation rate for indels with a > or =2-nt allele
      length difference was 58%, but the confirmation rate for indels with a 1-nt
      length difference was only 14%. The vast majority of the human diallelic indels
      were monomorphic in chimpanzees and gorillas. The ratio of
      deletionrcolon;insertion mutations was 4.1. Allele frequencies for the indels
      were measured in Europeans, Africans, Japanese, and Native Americans. New alleles
      were generally lower in frequency than old alleles. This tendency was most
      pronounced for the Africans, who are likely to be closest among the four groups
      to the original modern human population. Diallelic indels comprise approximately
      8% of all human polymorphisms. Their abundance and ease of analysis make them
      useful for many applications.

PMID- 12205566
TI  - Transmission of colistin-resistant Pseudomonas aeruginosa between patients
      attending a pediatric cystic fibrosis center.
AB  - We report on an outbreak of colistin-resistant Pseudomonas aeruginosa (CRPA) that
      occurred in a United Kingdom pediatric cystic fibrosis (CF) unit and involved six
      children over a period of 5 years. All CRPA-positive children had received
      aerosolized colistin therapy before first isolation of resistant organisms (mean
      duration, 3.1 years). Four of the 6 had also received courses of intravenous
      colistin in the year before the first isolation of CRPA. No impact of CRPA
      acquisition on respiratory function, clinical condition, or radiological
      parameters could be demonstrated. Four of the 6 children carried isolates of CRPA
      indistinguishable on genotyping. Two of these 4 children were sisters. The other
      2 were on the same ward together at time of first isolation, and subsequently
      shared overlapping admissions with one of the sisters. While there is no
      conclusive evidence for the route of transmission, the frequency of overlapping
      in-patient admissions between 3 of these patients is suggestive of patient-to
      patient transfer in the nosocomial setting.CF clinicians should be aware that
      colistin resistance can occur in P. aeruginosa, and some of these strains are
      capable of spread within CF units.

PMID- 12205567
TI  - Readmission with respiratory syncytial virus (RSV) infection among graduates from
      a neonatal intensive care unit.
AB  - We evaluated the incidence of readmission with respiratory syncytial virus (RSV)
      infection among the graduates of a regional Neonatal Intensive Care Unit (NICU),
      and characterized those who were rehospitalized. These data were used as a
      predictive tool to estimate the number of babies likely to suffer readmission
      with RSV for the year 2000 cohort. Using the published efficacies of palivizumab,
      the costs and benefits of protecting this cohort were assessed. Retrospective
      analysis of 2,507 NICU inpatient records from January 1, 1994-December 31, 1999
      from the Royal Maternity Hospital, Belfast, were compared with data on positive
      RSV samples from 1,790 patients between January 1, 1995-December 31, 1999 from
      the Northern Ireland Regional Virus Laboratory. The analysis yielded 136 (7.6%)
      ex-NICU patients among the positive RSV samples over this 5-year period.
      Characteristic seasonal peaks of RSV infection with interseasonal variability
      were observed. Of those readmitted, 86.9% were hospitalized with RSV before their
      first birthday. A calculated readmission rate of 5.4% for all NICU graduates, and
      6.4% for those <or=35 weeks, was found, leading to an expectation of 36
      readmissions from the 668 NICU graduates in the year 2000 over the next 1-2
      years, 20 of whom would be <or=35 weeks and 12 would be <or=32 weeks. A cost of
      pound 1.3 million would be required to protect the <or=35-week year 2000 cohort
      and prevent 11 readmissions. This equals pound 120,000 per admission prevented,
      or 28.2 patients treated to prevent 1 readmission. A readmission rate of 6.4% may
      differ from other studies, as it represents analysis of a greater number of RSV
      seasons. Using economic arguments alone, the cost of routine administration of
      Palivizumab to ex-NICU <or=35-week infants is prohibitive. A selective practice
      of immunizing those with chronic lung disease with a background of extreme
      prematurity over the November to March RSV season may be more cost-effective.

PMID- 12205568
TI  - Influence of lipopolysaccharide exposure on airway function and allergic
      responses in developing mice.
AB  - Exposure to endotoxin has been associated with an exacerbation of asthmatic
      responses in humans and animal models. However, recent evidence suggests that
      microbial exposure in early life may protect from the development of asthma and
      atopy. In this study, we sought to evaluate the effects of lipopolysaccaride
      (LPS) on airway function in developing mice. In addition, we evaluated the
      influence of LPS on subsequent allergen sensitization and challenge. Under light
      anesthesia, 2-3-week-old Balb/c mice received a single intranasal instillation of
      LPS or sterile physiologic saline. Measurements of airway function were obtained
      in unrestrained animals, using whole-body plethysmography. Airway responsiveness
      was expressed in terms of % enhanced pause (Penh) increase from baseline to
      aerosolized methacholine (Mch). In additional studies, we assessed the functional
      and cellular responses to ovalbumin sensitization and challenge following prior
      exposure to LPS. We found that exposure to LPS induced transient airway
      hyperresponsiveness to Mch. These functional changes were associated with the
      recruitment of neutrophils and lymphocytes into the bronchoalveolar lavage (BAL)
      fluid. Airway responsiveness after allergen sensitization and challenge was
      decreased by prior exposure to LPS. The analysis of BAL cells and cytokines
      (interferon-gamma and interleukin-4) did not reveal alterations in the overall
      Th1/Th2 balance. Our findings suggest that LPS leads to airway
      hyperresponsiveness in developing mice, and may protect against the development
      of allergen-driven airway dysfunction.

PMID- 12205570
TI  - Effectiveness and tolerability of high-dose salmeterol in cystic fibrosis.
AB  - The efficacy and tolerability of high-dose salmeterol (100 mcg, BID) and
      albuterol (2.5 mg, BID) were compared with those of albuterol (2.5 mg, BID) in
      outpatients with cystic fibrosis in a randomized, double-blind, double-dummy,
      placebo-controlled, crossover study with both short- (4 weeks of each) and long
      term (24 weeks of each) treatment periods. The primary outcome measure was the
      difference in mean change in forced expired volume in 1 sec (FEV(1)) from
      baseline to the end of each treatment, and secondary measures included changes in
      forced vital capacity (FVC), forced expiratory flow between 25-75% of FVC (FEF(25
      75)), patient-rated weekly symptom scores, number of extra (rescue) albuterol
      treatments, and number of antibiotic treatments. Tolerability was evaluated by
      changes in vital signs and adverse events.Thirty-six out of 44 patients enrolled
      finished the short-term treatment period, and 19 out of 23 who continued the
      study also finished the long-term treatment period. There was no significant
      difference in the mean % change in FEV(1) from baseline to completion of 4 weeks
      with each drug in the short-term treatment period (0.1% vs. 0.06%, albuterol vs.
      salmeterol; respectively). In the long-term treatment period, there was a
      significant decrease from baseline in FEV(1) with albuterol vs. salmeterol, as
      measured after both 12 and 24 weeks of each treatment (-6.2% vs. 1.8%, P = 0.013
      after 12 weeks, and -6.5% vs. 1.7%, P = 0.002, after 24 weeks, respectively). In
      both treatment periods, salmeterol was well-tolerated. While there were more
      rescue treatments per patient per week with albuterol than with salmeterol
      treatment in both the short- and long-term periods (0.67 vs. 0.40 and 1.76 vs.
      0.74, respectively), rescue treatments were needed significantly more often for
      only the long-term period with albuterol compared to salmeterol (P = 0.022).
      Also, there were more antibiotic interventions with albuterol than with
      salmeterol treatment in both the short- and long-term periods (25 vs. 10 and 56
      vs. 42, respectively); however, antibiotics were needed significantly more often
      for only the short-term period (P = 0.011). In addition, there was a
      significantly higher symptom score with albuterol vs. salmeterol treatment during
      the second half of the long-term period (1.24 vs. 0.89, P = 0.001).In conclusion,
      long-term high-dose salmeterol was equally safe and was associated with better
      pulmonary function, fewer interventions, and fewer respiratory symptoms compared
      to standard therapy with albuterol in a population of outpatients with mild to
      moderate CF.

PMID- 12205569
TI  - Pulmonary epithelial liquid absorption, expressed in relation to alveolar surface
      area, is reduced in fetal lambs following in utero tracheal occlusion.
AB  - We examined the effect of accelerated lung growth, induced by in utero tracheal
      occlusion (TO), on lung liquid uptake in near-term fetal sheep. In utero TO was
      performed in five fetal sheep at 110 days of gestation (term, approximately 145
      days); six SHAM operated fetuses served as controls. The rate of liquid movement
      across the pulmonary epithelium was measured, using a previously established
      technique, in anesthetized fetal sheep between 133-137 days of gestation during a
      2-hr adrenaline infusion (0.50 microg/min/kg, I.V.) and while lung luminal
      pressure was maintained at 5 mmHg. The rate of fetal lung liquid uptake was
      linear in all fetuses (mean r(2) < 0.97, n = 11). Mean values of lung liquid
      uptake expressed in relation to dry lung weight and luminal surface area of the
      right lung were significantly lower in TO fetuses (1.8 +/- 0.3 mL/hr/g and 1.0 +/
      0.2 mL/hr/m(2)) than in SHAM fetuses (2.6 +/- 0.2 mL/hr/g and 1.8 +/- 0.1
      mL/hr/m(2)); surface area of the right lung was 140% greater in TO fetuses than
      in SHAM fetuses. There was a linear relationship between lung liquid uptake and
      pulmonary epithelial surface area in SHAM animals, but not in TO fetuses. We
      hypothesize that loss of alveolar epithelial type-II cells induced by increased
      levels of fetal lung expansion may impair alveolar liquid clearance in the
      perinatal period.

PMID- 12205571
TI  - Invasive mechanical ventilation for acute respiratory failure in children with
      cystic fibrosis: outcome analysis and case-control study.
AB  - The outcome for cystic fibrosis (CF) patients requiring intubation and invasive
      mechanical ventilation (IMV) due to acute respiratory failure (ARF) has been
      poor. Mortality rates have been reported as high as 60-90%. However, a review of
      mortality in children has not been published in 20 years. Our objectives were to
      study outcomes in CF patients requiring IMV due to ARF between 1988-1998, compare
      recent outcomes with those previously reported, and identify risk factors
      associated with poor outcome. We additionally attempted to identify factors
      suggesting an increased risk of developing ARF requiring IMV. A retrospective
      cohort study design was used, comparing IMV survivors and nonsurvivors with a
      nested case-control study to identify risk factors for ARF leading to IMV. All
      patients cared for at our Center who required IMV for ARF between 1988-1998 were
      identified. Outcome, age, steroid use, forced vital capacity (FVC), forced
      expired volume in 1 sec (FEV(1)), microbiology, nutritional status, CF-related
      diabetes (CFRD), liver dysfunction, and history of major hemoptysis (HEM) or
      pneumothorax (PTX) were recorded. Cases were matched for gender and age with CF
      controls identified through a clinical database.Thirty-eight episodes of IMV due
      to ARF were reported in 33 patients. Three subjects underwent IMV on two or more
      occasions, but only the first episode was included in analysis. Older age was the
      only factor that was significantly associated with mortality: 9 subjects were <5
      years of age (mortality, 22%), while 24 were 5-34 years old (mortality, 75%) (P =
      0.013). There was an increased risk of having an episode of ARF requiring IMV in
      malnourished subjects (OR = 4.2; 95% CI = 1.66-10.51) and in those with a history
      of HEM (OR = 6.3; 95% CI = 1.75-22.65). Infants and young children with CF
      requiring IMV due to ARF have a favorable prognosis, whereas those >or=5 years of
      age suffer significantly higher mortality. Malnutrition and a history of HEM are
      important risk factors for having an episode of ARF requiring IMV.

PMID- 12205572
TI  - Airway obstruction in children with congenital heart disease: assessment by
      flexible bronchoscopy.
AB  - We assessed the spectrum of airway disorders in children with congenital cardiac
      anomalies, and reviewed our experience in using flexible bronchoscopy for
      assessment of airway problems in this patient group. The clinical records,
      flexible bronchoscopic findings, and cardiac imaging results of pediatric cardiac
      patients who presented with either clinical or radiological signs of airway
      obstruction between 1992-1999 were reviewed. Flexible bronchoscopic assessment
      was performed with the patients under sedation and topical anesthesia, using one
      of two bronchoscopes, i.e., an Olympus BFN20 or Olympus BF3C20. Of a total of 52
      patients, 33 had acyanotic cardiovascular lesions, the commonest being left-to
      right shunts (61%), while 19 had cyanotic heart lesions, with right ventricular
      outflow obstruction being the commonest (63%). Twenty-seven patients had
      undergone either surgical or transcatheter interventions. The median age at
      bronchoscopic assessment was 6 months (range, 4 days to 6 years). None of the
      patients developed significant procedural complications. A definitive diagnosis
      was made in 48 (92%) patients, 8 of whom had abnormalities involving only the
      upper airways, 35 only the lower airways, and 5 both. Abnormalities of the upper
      airway included laryngomalacia (n = 6), subglottic stenosis (n = 3), pharyngeal
      collapse (n = 2), and 1 each of choanal stenosis and supraglottitis. Extrinsic
      compression was the commonest lower airway abnormality that was found in 27/40
      patients (67%), with a predilection for the left main bronchus (18/27, 67%). The
      structures that caused extrinsic compression included dilated pulmonary arteries
      with or without left atrial dilation (n = 20), an anomalous aortic or pulmonary
      arterial course (n = 3), a dilated aorta (n = 1), and a shunt (n = 1), but were
      not obvious in 2 patients. Intrinsic lower airway abnormalities included
      bronchomalacia (n = 4), tracheal stenosis (n = 4), and one each of variant
      bronchial bifurcation and a pouch arising from the tracheal wall. Intraluminal
      mucus plugging of the lower airways occurred in the remaining 3 patients.
      Children with congenital heart disease are at risk of airway obstruction both
      before and after surgery. Flexible bronchoscopy, being safe and effective in
      diagnosing airway disorders in this patient group, should be considered as the
      first line of investigation.

PMID- 12205573
TI  - Within- and between-day variability of respiratory impedance, using impulse
      oscillometry in adolescent asthmatics.
AB  - The objectives of the present study were to: 1) assess spirometric indices and
      respiratory impedance with forced oscillation (FO), using impulse oscillometry
      (IOS) in clinically stable asthmatic children over 3 consecutive days; 2) assess
      FO reactance (X), using an integrated index and resistance (R) separately during
      inspiration and expiration; and 3) assess effects on FO of hand support of cheeks
      vs. no hand support. Our hypotheses were: 1) because of increased sensitivity,
      IOS manifests day-to-day variability not demonstrable by spirometry; 2) IOS R
      during expiration exceeds that during inspiration; and 3) hand support of cheeks
      affects IOS R and X only minimally. We obtained triplicate twice-daily measures
      of IOS R and X in asthmatic adolescents at summer camp, in a convenience sample
      of children willing, with parental permission, to undergo repeated testing on
      consecutive days. Subjects received all medications between 6:30-7:30 AM, and
      were bronchodilated at time of testing. Subjects underwent IOS tests without hand
      support of cheeks, followed by tests with both hands supporting cheeks. ANOVA and
      regression analyses were used to discern technique differences.Significant
      differences in IOS inspiratory R5, R5 - R15 (frequency dependence of R), and low
      frequency reactance area (AX) occurred across 3 days, but spirometric indices
      were unchanged. Inspiratory R at 5 Hz (R5) was significantly smaller than
      expiratory R5 (P < 0.0001). ANOVA revealed no significant differences between
      hand and facial muscle cheek support for IOS R and X below 15 Hz, but significant
      differences occurred above 15 Hz. In conclusion, inspiratory R5, R5 - R15, and AX
      are sensitive measures for detecting changes in bronchomotor tone in adolescent
      asthmatic subjects, while expiratory R5 may be influenced by additional factors.
      Manual support of cheeks does not appear to affect IOS indices of peripheral
      airway obstruction in adolescent asthmatics. IOS is a practical method for
      quantifying respiratory mechanics, and its potential role in disease management
      warrants further study.

PMID- 12205574
TI  - Unusual case of stridor and wheeze in an infant: tracheal bronchogenic cyst.
AB  - Bronchogenic cysts are congenital anomalies that represent aberrant development
      of the foregut. Bronchogenic cysts in the mediastinum have been documented in
      both children and adults, but only one case of tracheal bronchogenic cyst in an
      infant was found in the literature. We report on a case of an infant with wheeze,
      stridor, and retractions, caused by a midtracheal bronchogenic cyst. This entity,
      with its unusual location, should be considered in the differential diagnosis of
      respiratory distress, cyanotic spells, wheezing, and stridor in infants.

PMID- 12205575
TI  - Recurrent unilateral bacterial pneumonias and interstitial fibrosis associated
      with pulmonary vein atresia: successful treatment with endovascular stent
      implantation.
AB  - A variety of pulmonary vascular disorders, such as hemangiomatosis,
      telangectasia, and veno-occlusive disease, may be involved in the pathogenesis of
      interstitial lung diseases. We describe the case of a girl with recurrent
      bacterial pneumonia and progressive interstitial fibrosis affecting the right
      lung. Morphologic evaluation of the lung biopsy showed structural changes of the
      vessel walls suggesting pulmonary hypertension. The echocardiogram showed the
      presence of centripetal blood flow in the right pulmonary artery from the
      periphery of the lung to the heart. A selective right angiography demonstrated
      the presence of pulmonary venous obstruction at the veno-atrial junction,
      successfully treated by endovascular stent implantation during cardiac
      catheterization.

PMID- 12205577
TI  - Analysis of the spatial characteristics of metabolic abnormalities in newly
      diagnosed glioma patients.
AB  - PURPOSE: To evaluate the role of 3D MR spectroscopic imaging (MRSI) as a tool for
      characterizing heterogeneity within a lesion in glioma patients. MATERIALS AND
      METHODS: Forty-nine patients with newly diagnosed glioma were studied with 3D
      water-suppressed proton (1-H) MRSI. Signal intensities from choline (Cho),
      creatine (Cr), N-acytel aspartate (NAA), and lactate/lipid (LL) were estimated
      from the spectra. Regions of interest (ROIs) corresponding to the metabolic
      abnormalities were defined and compared with the anatomic lesions. RESULTS: This
      study showed that the tumor burden measured with either the volumes of the
      metabolic abnormalities or the metabolic levels in the most abnormal voxels was
      correlated with the degree of malignancy of the tumor. The volumes of elevated
      Cho and decreased NAA were useful for distinguishing low-grade from high-grade
      lesions. The volume of abnormal LL was correlated with the existence of necrosis
      and with the volume of contrast-enhancing lesions in high-grade lesions. The
      differences in the volume of abnormal LL were also statistically significant
      between patients in each grade. CONCLUSION: These 3D-MRSI data provide important
      additional information to conventional MRI for evaluating and characterizing
      gliomas.

PMID- 12205578
TI  - High-resolution selective three-dimensional magnetic resonance coronary
      angiography with navigator-echo technique: segment-by-segment evaluation of
      coronary artery stenosis.
AB  - PURPOSE: To investigate the feasibility of high-resolution selective three
      dimensional (3D) magnetic resonance coronary angiography (MRCA) in the evaluation
      of coronary artery stenoses. MATERIALS AND METHODS: In 12 patients with coronary
      artery stenoses, MRCA of the coronary artery groups, including the coronary
      segments with stenoses of 50% or greater based on conventional x-ray coronary
      angiography (CAG), was performed with double-oblique imaging planes by orienting
      the 3D slab along the major axis of each right coronary artery-left circumflex
      artery (RCA-LCX) group and each left main trunk-left anterior descending artery
      (LMT-LAD) group. Ten RCA-LCX and five LMT-LAD MR angiograms were obtained, and
      the results were compared with those of conventional x-ray angiography. RESULTS:
      Among 70 coronary artery segments expected to be covered, a total of 49 (70%)
      segments were fully demonstrated in diagnostic quality. The identification of
      segmental location of stenoses showed as high an accuracy as 96%. The
      retrospective analysis for stenosis of 50% or greater yielded the sensitivity,
      specificity, and accuracy of 80%, 85%, and 84%, respectively. CONCLUSION:
      Selective 3D MRCA has the potential for segment-by-segment evaluation of major
      portions of the right and left coronary arteries with high accuracy.

PMID- 12205579
TI  - Estimation of left ventricular performance through temporal pressure variations
      measured by MR velocity and acceleration mappings.
AB  - PURPOSE: To describe a method for assessing pressure variation vs. time (dp/dt)
      using blood flow acceleration measured by MRI, and to demonstrate its
      applicability in estimating left ventricular (LV) function. MATERIALS AND
      METHODS: The method was tested in vitro using a pulsatile phantom, and a strong
      correlation was found between transducer and MRI determinations of dp/dt (r =
      0.98). Selected aortic flow parameters were then measured in 10 patients and the
      results were compared with transducer measurements of the LV dp/dt. RESULTS: The
      correlation coefficients for the reference estimations of global myocardial
      function and MRI were 0.59 for aortic velocity, 0.74 for aortic acceleration, and
      0.86 for aortic dp/dt. CONCLUSION: MR measurements of velocity and acceleration
      within the ascending aorta offer a noninvasive method for determining indices,
      such as the aortic dp/dt, that are closely correlated with the global myocardial
      contractility function.

PMID- 12205580
TI  - Comparison of right ventricular volume measurement between segmented k-space
      gradient-echo and steady-state free precession magnetic resonance imaging.
AB  - PURPOSE: To compare right ventricular volume measurements and their
      reproducibility between steady-state free precession (SSFP) and conventional
      turbo gradient-echo (TGE) imaging. MATERIALS AND METHODS: Right ventricular
      volumes and observer variabilities were compared between SSFP and TGE in 31
      subjects (21 normal volunteers and 10 subjects with heart failure). For further
      internal validation of the right ventricular volumes, the left ventricle (LV) and
      right ventricle (RV) stroke volumes were compared for the normal volunteers.
      RESULTS: The volumes as measured by SSFP were significantly larger than for TGE
      (mean bias end-diastolic volume [EDV] 11.1 +/- 14.2, end-systolic volume [ESV]
      9.8 +/- 9.75). SSFP had lower interobserver variability (SSFP EDV -10.1 +/- 11.6
      vs. TGE EDV -6.2 +/- 18.5) and intra-observer variability (SSFP EDV -2.0 +/- 6.3
      vs. TGE EDV -6.1 +/- 14.8). The mean absolute differences between LV and RV
      stroke volumes for 21 normal volunteers were: TGE 5.8 +/- 12.9 (r(2) = 0.72),
      SSFP 4.6 +/- 6.9 (r(2) = 0.92). CONCLUSION: SSFP and TGE yield different
      measurement values of RV volumes with SSFP, providing a more reproducible
      measurement.

PMID- 12205581
TI  - Double arterial phase dynamic MRI with sensitivity encoding (SENSE) for
      hypervascular hepatocellular carcinomas.
AB  - PURPOSE: To investigate the efficacy of SENSE MRI, including the double arterial
      phase dynamic study, to detect hypervascular hepatocellular carcinomas (HCCs).
      MATERIALS AND METHODS: MRI of the liver was performed in 40 consecutive patients
      (20 by conventional MRI and 20 by SENSE MRI). The SENSE technique was used to
      obtain breath-hold T1-weighted FSE images (TR/TE = 556/12 msec), respiratory
      triggered T2-weighted FSE images (TR/TE = 1800/90 msec) with and without fat
      suppression, and dynamic MR images (TR/TE/FA = 160-168/4.6 msec/70 degrees ). In
      each arterial dominant phase and portal dominant phase, two scans were
      consecutively performed with one breath-hold, leading to the double arterial
      phase and double portal phase images with SENSE. RESULTS: The sensitivity of
      SENSE MRI for HCCs diagnosed from all MR images, including dynamic study, T1
      weighted images, and T2-weighted images, was 91.7%, while that of conventional
      MRI was 76.3%. The positive predictive value of SENSE MRI for HCCs was 91.7%,
      while that of conventional MRI was 87.9%. In terms of HCCs < or = 10 mm, the
      sensitivity and positive predictive values of SENSE MRI were 78.6% and 78.6%,
      respectively, while those of conventional MRI were 27.3% and 60.0%, respectively.
      The number of detected HCCs < or = 10 mm was significantly larger in SENSE MRI
      than in conventional MRI (P < 0.05). The cause of false-positive lesions on SENSE
      MR images was an arterioportal shunt. CONCLUSION: SENSE MRI with double arterial
      phase dynamic study showed higher sensitivity compared to the conventional
      technique. Therefore, SENSE MRI is a promising method for the detection of HCC.

PMID- 12205582
TI  - Image-guided surgery for anal fistula in a 0.5T interventional MRI unit.
AB  - PURPOSE: To determine whether MR-guided anorectal surgery is feasible, and to
      develop techniques for MR-guided anal fistula surgery. MATERIALS AND METHODS: Six
      patients with pilonidal sinus (PNS), and 21 with suspected anal fistulae were
      operated on in the GE Signa SPIO 0.5T interventional MRI unit. Procedures were
      performed with magnet-safe Lockhart-Mummery fistula probes. Preprocedural and
      intra-operative MRI (IOMRI) techniques were used to identify the extent of the
      fistula tracts and septic foci, and to ensure the adequacy of the surgical
      procedure. RESULTS: IOMRI demonstrated the PNS lesions and the adequacy of
      excision. Imaging failed to demonstrate a fistula in two patients, as confirmed
      by surgical examination. No images were obtained in one patient due to his size
      (weight in excess of 100 kg). In 18 patients a fistula tract or abscess was
      demonstrated and IOMRI was used to assess the adequacy of the surgical procedure.
      In three patients this demonstrated incomplete drainage of septic foci, which was
      not obvious on inspection of the surgical field. We believe that in these
      patients IOMRI prevented an incomplete procedure and the potential requirement
      for a second operation. Further surgery was performed to rectify this situation.
      The fistula tract was laid open in 13 patients, and a Seton drain was inserted in
      five. CONCLUSION: MRI-guided surgery for anal fistula is feasible. IOMRI
      demonstrates the exact anatomy of the tracts and abscesses, and confirms that all
      have been adequately treated. We believe it may become particularly useful in
      surgery for recurrent and complex anal fistulae, and may lead to fewer
      recurrences.

PMID- 12205583
TI  - Evaluation of tissue perfusion in a rat model of hind-limb muscle ischemia using
      dynamic contrast-enhanced magnetic resonance imaging.
AB  - PURPOSE: To evaluate the feasibility of using dynamic contrast-enhanced magnetic
      resonance imaging (MRI) for assessment of muscle perfusion in a rat model of hind
      limb ischemia. MATERIALS AND METHODS: The acute alteration and chronic recovery
      in muscle perfusion and perfusion reserve after femoral artery ligation were
      quantified using the maximum Gd-DTPA uptake rate obtained by a T(1)-weighted
      gradient-recalled echo sequence. Radionuclide-labeled microsphere blood flow
      measurements were performed for comparison with the MR perfusion measurement on a
      separate set of animals. RESULTS: After femoral artery ligation, a significant
      reduction in resting muscle perfusion was only observed at 1 hour post-ligation
      during the 28-day follow-up period. Muscle perfusion reserve was severely
      diminished following the ligation. Despite significant recovery over time,
      perfusion reserve to the ligated limb reached only 63% of the perfusion capacity
      in the unaffected limb by 42 days post ligation. A strong correlation (r = 0.86)
      between MR perfusion and microsphere blood flow measurements was observed for
      evaluation of relative changes in muscle perfusion. CONCLUSION: Dynamic contrast
      enhanced MRI with Gd-DTPA is useful to assess time-dependent changes in muscle
      perfusion and perfusion reserve in this hind-limb ischemia model.

PMID- 12205584
TI  - Characterization of hematopoietic bone marrow in male professional cyclists by
      magnetic resonance imaging of the lumbar spine.
AB  - PURPOSE: To prospectively evaluate hematopoietic bone marrow of male professional
      cyclists in relation to performance data and laboratory data, and in comparison
      to age-matched healthy volunteers. MATERIALS AND METHODS: Twenty male cyclists
      and 44 volunteers (27 males and 17 females) were prospectively studied by
      magnetic resonance imaging (MRI) at high-field strength. A sagittal T1-weighted
      (T1-w) spin-echo (SE) sequence, a gradient-echo (GE) sequence with an echo time
      (TE) for out-of-phase (OOP) imaging, and a turbo inversion-recovery sequence with
      short inversion time (TIRM) for fat suppression was used. The averaged bone
      marrow signal intensity (SI) of three adjacent vertebrae was related to the
      signal of an adjacent nondegenerative disk. RESULTS: The cyclists revealed a
      significantly different SI as compared to male volunteers in the OOP (0.34 +/-
      0.14 vs. 0.28 +/- 0.09, P < 0.05) and T1-w sequences (1.62 +/- 0.19 vs. 1.77 +/-
      0.30, P < 0.05). Only in TIRM was there a significant difference compared to
      female volunteers (0.36 +/- 0.08 vs. 0.44 +/- 0.04, P < 0.01). MRI data of
      cyclists did not correlate to hemoglobin, erythrocyte, or reticulocyte counts;
      ferritin, relative heart volume, relative maximal power (rPmax; W/kg bw), or
      relative maximal oxygen consumption (VO(2)max). A borderline linear correlation
      was found for hematocrit (OOP: r = 0.42, P = 0.06; TIRM: r = 0.44, P = 0.06).
      CONCLUSION: Bone marrow hyperplasia is observed in male professional cyclists in
      the axial skeleton. The MR findings are probably independent of mechanically
      induced marrow edema. A multifactorial cause must be considered, as single
      laboratory and performance data did not appear to contribute significantly to
      these results.

PMID- 12205585
TI  - Parametric imaging of tumor perfusion using flow- and permeability-limited
      tracers.
AB  - PURPOSE: To quantitatively evaluate the spatial distribution of flow- and
      permeability-limited perfusion in MCF7 human breast cancer tumors orthotopically
      implanted in CD1-NU mice. MATERIALS AND METHODS: Flow-limited perfusion was
      derived from (2)H-MRI recorded before and after infusion of deuterated water.
      Permeability-limited perfusion was evaluated from GdDTPA-enhanced (1)H-MRI.
      RESULTS: The dominant processes in tumor perfusion, namely blood flow and
      capillary permeability, were mapped in orthotopically implanted MCF7 human breast
      cancer tumors. The dynamic data were processed according to physiological models,
      yielding parametric maps of intravascular volume fraction, water perfusion rate,
      GdDTPA permeability rate constant, and extracellular volume fraction accessible
      to GdDTPA. The maps exhibited the heterogeneous distribution of each perfusion
      parameter. Most of the tumor tissue (> or =95%) was perfused with HDO, while
      GdDTPA was perfused in only about 50% of it. In most loci the perfusion rate was
      limited by capillary permeability to GdDTPA. CONCLUSION: The results demonstrated
      the instructive value of tracers with different properties used in conjunction to
      achieve a deeper understanding of tumor perfusion capacity. This study offers
      tools for the accurate, noninvasive evaluation of drug delivery efficacy.

PMID- 12205586
TI  - Hybrid phased array for improved internal auditory canal imaging at 3.0-T MR.
AB  - PURPOSE: To develop and evaluate a hybrid phased array for internal auditory
      canal (IAC) imaging at 3.0 T. MATERIALS AND METHODS: A hybrid phased array was
      designed and built as two circular surface receive-only coils combined with a
      volume transmit-receive birdcage head coil for simultaneous image acquisition.
      Phantom and volunteer images were obtained to assess the coil performance.
      RESULTS: The phantom data show that significant signal-to-noise ratio (SNR)
      improvement was achieved in the region corresponding to the inner ear, i.e., by a
      factor of 2.5 compared to the standard head coil data. Volunteer IAC image
      quality was deemed superior as compared to images acquired at 3.0 T using a
      standard head coil. CONCLUSION: This hybrid array combined with three-dimensional
      fast spin-echo (FSE) acquisition resulted in improved high spatial resolution IAC
      imaging.

PMID- 12205587
TI  - Comparison of automated and manual MRI volumetry of hippocampus in normal aging
      and dementia.
AB  - PURPOSE: To determine whether automatic and manual measurements of hippocampal
      volume differences on MRI between normal aging, cognitive impairment (CI), and
      Alzheimer's disease (AD) yield similar results. MATERIALS AND METHODS:
      Reliability was determined for an automatic and a manual method on nine
      volunteers (22-83 years old) who underwent MRI twice in 1 day. Hippocampal
      volumes of 20 cognitively normal subjects (mean age 74.0 +/- 6.2 years) and age
      matched patients (20 CI and 20 AD) were compared. RESULTS: The intraclass
      correlation for automatic calculations of hippocampal volume was 0.94; for manual
      tracing it was 0.99. Volume differences between cognitively normal, CI, and AD
      subjects from the automatic and manual methods were similar. CONCLUSION: Because
      the automatic calculations were faster and less susceptible to rater bias than
      manual tracing, this automated method is expected to be very useful for analyzing
      hippocampal changes in studies of aging and dementia.

PMID- 12205588
TI  - Dynamic coronary MR angiography and first-pass perfusion with intracoronary
      administration of contrast agent.
AB  - PURPOSE: To evaluate whether dynamic imaging of the coronary arteries can be
      performed with intracoronary infusion of low-dose gadolinium (Gd)-based contrast
      agent and assess the effect of long duration and multiple infusions on the image
      signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR). MATERIALS AND
      METHODS: Dynamic coronary magnetic resonance (MR) imaging (130 msec/image) and
      contrast agent first pass myocardial perfusion studies were performed with
      intracoronary infusions of low-dose Gd-based MR contrast agent on dogs (N = 4)
      using a fast multislice gradient recalled echo (GRE) sequence. RESULTS: Contrast
      enhanced coronary arteries were clearly imaged during infusion periods as long as
      2.3 minutes. The SNR and CNR of the contrast-enhanced coronary arteries remained
      essentially unchanged over multiple consecutive angiographic sessions. In
      addition, we demonstrated that first pass studies performed with intracoronary
      injection of MR contrast agent can be used as a means of assessing regional
      myocardial perfusion. CONCLUSION: These studies demonstrated that, using
      intracoronary infusion of Gd, coronary magnetic resonance angiography (MRA) can
      be performed with high temporal resolution, and multiple low-dose slow infusions
      of Gd-based MR contrast agent can be performed without compromise of the vessel
      SNR and CNR.

PMID- 12205589
TI  - Myocardial tagging with 3D-CSPAMM.
AB  - PURPOSE: To introduce a true three-dimensional (3D) tagging technique for the
      assessment of myocardial tissue motion. MATERIALS AND METHODS: To generate a 3D
      tagging grid, a complementary spatial modulation of magnetization (CSPAMM) was
      applied in three spatial directions. Imaging was performed using a conventional
      fast 3D gradient-echo sequence. For automatic analysis of the 3D-CSPAMM data set,
      evaluation software, based on a 3D extension of the HARP technique, was used.
      RESULTS: Successful application of the 3D-CSPAMM technique in healthy subjects
      allowed the accurate determination of quantitative 3D motion patterns in the
      human heart. CONCLUSION: 3D-CSPAMM may contribute to the quantification of the
      local 3D myocardial motion pattern throughout the cardiac cycle.

PMID- 12205590
TI  - What is the role of proton MR spectroscopy of the lumbar spine in patients with
      glycogen storage disease type Ib?

PMID- 12205592
TI  - Abstracts of the 127th Annual Meeting of the American Neurological Association.
      October 12-16, 2002. New York, New York, USA.

PMID- 12205623
TI  - Abstracts of the 31st Annual Meeting of the Child Neurology Society. October 9
      12, 2002. Washington DC, USA.

PMID- 12205636
TI  - The ever-stimulating association of smoking and coffee and Parkinson's disease.

PMID- 12205637
TI  - Tauists, Baptists, Syners, Apostates, and new data.

PMID- 12205638
TI  - Cell transplantation for stroke.
AB  - Cell transplantation has emerged as an experimental approach to restore brain
      function after stroke. Various cell types including porcine fetal cells, stem
      cells, immortalized cell lines, and marrow stromal cells are under investigation
      in experimental and clinical stroke trials. This review discusses the unique
      advantages and limitations of the different graft sources and emphasizes the
      current, limited knowledge about their biology. The survival, integration, and
      efficacy of neural transplants in stroke patients will depend on the type,
      severity, chronicity, adequacy of circulation, and location of the stroke lesion.

PMID- 12205639
TI  - A meta-analysis of coffee drinking, cigarette smoking, and the risk of
      Parkinson's disease.
AB  - We conducted a systematic review to summarize the epidemiological evidence on the
      association between cigarette smoking, coffee drinking, and the risk of
      Parkinson's disease. Case-control and cohort studies that reported the relative
      risk of physician-confirmed Parkinson's disease by cigarette smoking or coffee
      drinking status were included. Study-specific log relative risks were weighted by
      the inverse of their variances to obtain a pooled relative risk and its 95%
      confidence interval (CI). Results for smoking were based on 44 case-control and 4
      cohort studies, and for coffee 8 case-control and 5 cohort studies. Compared with
      never smokers, the relative risk of Parkinson's disease was 0.59 (95% CI, 0.54
      0.63) for ever smokers, 0.80 (95% CI, 0.69-0.93) for past smokers, and 0.39 (95%
      CI, 0.32-0.47) for current smokers. The relative risk per 10 additional pack
      years was 0.84 (95% CI, 0.81-0.88) in case-control studies and 0.78 (95% CI, 0.73
      0.84) in cohort studies. Compared with non-coffee drinkers, relative risk of
      Parkinson's disease was 0.69 (95% CI, 0.59-0.80) for coffee drinkers. The
      relative risk per three additional cups of coffee per day was 0.75 (95% CI, 0.64
      0.86) in case-control studies and 0.68 (95% CI, 0.46-1.00) in cohort studies.
      This meta-analysis shows that there is strong epidemiological evidence that
      smokers and coffee drinkers have a lower risk of Parkinson's disease. Further
      research is required on the biological mechanisms underlying this potentially
      protective effect.

PMID- 12205640
TI  - Astrocyte-specific TSC1 conditional knockout mice exhibit abnormal neuronal
      organization and seizures.
AB  - Persons affected with tuberous sclerosis complex (TSC) develop a wide range of
      neurological abnormalities including aberrant neuronal migration and seizures. In
      an effort to model TSC-associated central nervous system abnormalities in mice,
      we generated two independent lines of astrocyte-specific Tsc1 conditional
      knockout mice by using the Cre-LoxP system. Astrocyte-specific Tsc1-null mice
      exhibit electroencephalographically proven seizures after the first month of age
      and begin to die at 3 to 4 months. Tsc1-null mice show significant increases in
      astrocyte numbers throughout the brain by 3 weeks of age and abnormal neuronal
      organization in the hippocampus between 3 and 5 weeks. Moreover, cultured Tsc1
      null astrocytes behave similar to wild-type astrocytes during log phase growth
      but demonstrate increased saturation density associated with reduced p27(Kip1)
      expression. Collectively, our results demonstrate that astrocyte-specific
      disruption of Tsc1 in mice provides a context-dependent growth advantage for
      astrocytes that results in abnormalities in neuronal organization and epilepsy.

PMID- 12205641
TI  - Complex segregation analysis of restless legs syndrome provides evidence for an
      autosomal dominant mode of inheritance in early age at onset families.
AB  - A strong familial component of restless legs syndrome (RLS) is known. The
      objective of this study therefore was to investigate the likely mode of
      inheritance of RLS. RLS patients and their first-degree relatives were
      investigated and classified in RLS affected and RLS nonaffected subjects.
      Assessments were based on direct, personal standardized diagnostic interviews.
      Complex segregation analysis was performed with the families stratified according
      to the mean age at onset of the disease within the families. Two hundred thirty
      eight RLS patients, 537 first-degree relatives, and 133 spouses were interviewed.
      Two groups of families were stratified: mean age at onset up to 30 years of age
      (Group A) and older than 30 years (Group B; p < 0.005). In Group A, segregation
      analysis strongly favored a single major gene acting autosomal dominant with a
      multifactorial component. Parameter estimates were 0.003 for the allele
      frequency, 1.0 for the penetrance, and 0.005 for the phenocopy rate. In Group B,
      no evidence for a major gene could be elucidated. The segregation pattern found
      in our families argues for an autosomal allele acting dominantly in RLS families
      with an early age at onset of symptoms and suggests that RLS is a causative
      heterogeneous disease.

PMID- 12205642
TI  - Status epilepticus in a population-based cohort with childhood-onset epilepsy in
      Finland.
AB  - Little is known about the time course over which status epilepticus occurs in
      childhood-onset epilepsy and its impact on long-term prognosis. A population
      based cohort of 150 children younger than age 16 years with new onset epilepsy
      between 1961 and 1964 residing in the catchment area of Turku University Hospital
      was observed prospectively until 1997. The occurrence of status epilepticus and
      recurrent status epilepticus, risk factors for status epilepticus, and the impact
      of status epilepticus on prognosis were examined. Of the 150 cases, 41 patients
      (27%) experienced an episode of status epilepticus of whom 22 patients (56%) had
      two or more episodes. The risk of status epilepticus was highest at the onset of
      the disorder with 30 (73%) cases occurring before (n = 12) or at (n = 18) onset
      and 37 (90%) cases within 2 years of onset. On multivariable analysis, risk
      factors for status epilepticus included remote symptomatic cause, age of onset 6
      years or younger, and partial seizures. Specific epilepsy syndromes also were
      associated with a differential risk of status epilepticus. The occurrence of
      status epilepticus did not alter the mortality rates and had only a modest impact
      on the probability of attaining remission. In subjects with no other neurological
      handicap, social and educational outcomes were similar in those with status
      epilepticus and those with no history of status epilepticus. We conclude that
      status epilepticus is a common occurrence in childhood-onset epilepsy. When it
      does occur, it occurs early in the course of the disorder. The occurrence of
      status epilepticus does not appear to have significant adverse impact on long
      term prognosis of childhood-onset epilepsy.

PMID- 12205643
TI  - Mitochondrial DNA depletion and dGK gene mutations.
AB  - Mitochondrial DNA depletion syndrome is a clinically heterogeneous group of
      disorders characterized by a reduction in mitochondrial DNA copy number. The
      recent discovery of mutations in the deoxyguanosine kinase (dGK) gene in patients
      with the hepatocerebral form of mitochondrial DNA depletion syndrome prompted us
      to screen 21 patients to determine the frequency of dGK mutations, further
      characterize the clinical spectrum, and correlate genotypes with phenotypes. We
      detected mutations in three patients (14%). One patient had a homozygous GATT
      duplication (nucleotides 763-766), and another had a homozygous GT deletion
      (nucleotides 609-610); both mutations lead to truncated proteins. The third
      patient was a compound heterozygote for two missense mutations (R142K and E227K)
      that affect critical residues of the protein. These mutations were associated
      with variable phenotypes, and their low frequencies suggests that dGK is not the
      only gene responsible for mitochondrial DNA depletion in liver. The patient with
      the missense mutations had isolated liver failure and responded well to liver
      transplantation, which may be a therapeutic option in selected cases.

PMID- 12205644
TI  - Hyperthermia induces age-dependent changes in rat hippocampal excitability.
AB  - The mechanisms underlying the generation of febrile seizures are poorly
      understood. This study investigated hyperthermia-induced changes in the
      hippocampus, a structure implicated in febrile seizures. It was hypothesized that
      neuronal excitability in the hippocampus changes with increasing temperature, and
      that this change is different in adult as compared with immature rats. Adult and
      immature (15-17 days postnatal) male rats were studied under urethane anesthesia
      during normothermia, moderate hyperthermia (38-39.5 degrees C), and severe
      hyperthermia (>39.5 degrees C). Paired-pulse inhibition of the orthodromically
      activated population spikes in the dentate gyrus and cornu ammonis 1 region of
      the hippocampus (CA1), two structures within the hippocampus, was measured after
      stimulation of the medial perforant path and Schaffer collaterals, respectively.
      In the adult rat, paired-pulse inhibition was increased in the dentate gyrus
      during moderate and severe hyperthermia but decreased in CA1 during severe
      hyperthermia (all p values < 0.05). In the immature rat, paired-pulse inhibition
      was unchanged in the dentate gyrus but decreased in CA1 during moderate
      hyperthermia (p < 0.05). We suggest that hyperthermia contributes to seizure
      susceptibility in the immature hippocampus by decreasing CA1 inhibition. In the
      adult rat, a decrease in CA1 inhibition requires a higher degree of hyperthermia,
      and hippocampal seizure generation is opposed by an increase in dentate gyrus
      inhibition.

PMID- 12205645
TI  - Exploring white matter tracts in band heterotopia using diffusion tractography.
AB  - Band heterotopia is a malformation of cortical development characterized by bands
      of gray matter in the white matter parallel to the surface of the neocortex.
      Histopathological studies have suggested that small white matter tracts pass
      through the heterotopia, and functional magnetic resonance imaging studies have
      shown activation in the malformation. We used diffusion tractography to explore
      the anatomical connectivity of band heterotopia and, in particular, whether in
      vivo white matter tracts traverse the heterotopic gray matter. Five patients with
      band heterotopia and five control subjects were scanned with whole brain
      diffusion tensor imaging. Anisotropy maps were calculated. Using fast marching
      tractography, we produced maps of connectivity and tract traces from two seed
      points, in the splenium of the corpus callosum and the right parietal lobe.
      Eigenvectors were found to pass through the band heterotopia in an aligned
      fashion. Patterns for maps of connectivity were similar in patients and control
      subjects. Areas of high connectivity were found in the band heterotopia and in
      cortical areas on the far side of the malformation from the seed point. The
      tracts hence appeared to traverse or end within the band heterotopia. The results
      are in agreement with previous histopathological studies and indicate the
      structural basis of the functional connectivity and absence of focal deficits in
      these patients.

PMID- 12205646
TI  - Periventricular cerebral white matter lesions predict rate of cognitive decline.
AB  - The prospect of declining cognitive functions is a major fear for many elderly
      persons. Cerebral white matter lesions, as commonly found with magnetic resonance
      imaging, have been associated with cognitive dysfunction in cross-sectional
      studies. Only a few longitudinal studies using small cohorts confirmed these
      findings. We examined the relation between severity of white matter lesions and
      cognitive decline over a nearly 10-year period in 563 elderly subjects sampled
      from the general nondemented Dutch population. Severity of white matter lesions
      was scored for periventricular and subcortical regions separately using an
      extensive semiquantitative scale. Cognitive function was measured by the Mini
      Mental State Examination at regular time intervals during 1990 to 2000, and
      magnetic resonance imaging scans were made in 1995 to 1996. More severe white
      matter lesions were associated with more rapid cognitive decline over a mean
      follow-up period of 7.3 years (standard deviation, 1.5). After adjusting for age,
      gender, educational level, measures of depression, and brain atrophy and
      infarcts, subjects with severe periventricular white matter lesions experienced
      cognitive decline nearly three times as fast (0.28 Mini-Mental State Examination
      points/year [95% confidence interval, 0.20-0.36]) as the average (0.10
      points/year [95% confidence interval, 0.09-0.11]). There was no independent
      relationship between severity of subcortical white matter lesions and rate of
      cognitive decline.

PMID- 12205647
TI  - Midodrine in neurally mediated syncope: a double-blind, randomized, crossover
      study.
AB  - Neurally mediated syncope is the most frequent cause of syncope in patients
      without structural heart disease. Its most common trigger is a reduction in
      venous return to the heart due to excessive venous pooling in the legs. We
      conducted a double-blind, randomized, crossover trial to investigate the efficacy
      of midodrine, a selective alpha-1 adrenergic agonist that decreases venous
      capacitance, in preventing neurally mediated syncope triggered by passive head-up
      tilt. Twelve patients with history of recurrent neurally mediated syncope, which
      was reproduced during head-up tilt, were randomized to receive a nonpressor dose
      of midodrine (5mg) or placebo on day 1 and the opposite on day 3. One hour after
      drug or placebo administration, patients underwent 60-degree head-up tilt lasting
      40 minutes (unless hypotension or bradycardia developed first). In the supine
      position, midodrine produced no significant change in blood pressure or heart
      rate. The responses to head-up tilt were significantly different on the midodrine
      and the placebo day: on the placebo day, 67% (8/12) of the subjects suffered
      neurally mediated syncope, whereas only 17% (2/12) of the subjects developed
      neurally mediated syncope on the midodrine day (p < 0.02). These results indicate
      that midodrine significantly improves orthostatic tolerance during head-up tilt
      in patients with recurrent neurally mediated syncope.

PMID- 12205648
TI  - Treatment with simvastatin in normocholesterolemic patients with Alzheimer's
      disease: A 26-week randomized, placebo-controlled, double-blind trial.
AB  - In a randomized, placebo-controlled, double-blind study, we investigated whether
      statins alter cholesterol metabolites and reduce Abeta levels in the
      cerebrospinal fluid of 44 patients with Alzheimer's disease. Individuals were
      given up to 80mg simvastatin daily or placebo for 26 weeks. Overall, simvastatin
      did not significantly alter cerebrospinal fluid levels of Abeta40 and Abeta42. In
      post hoc analysis, simvastatin significantly decreased Abeta40 levels in the
      cerebrospinal fluid of patients with mild Alzheimer's disease. The reduction of
      Abeta40 correlated with the reduction of 24S-hydroxycholesterol. These changes
      were not observed in more severely affected patients.

PMID- 12205649
TI  - Niemann-Pick type C disease: accelerated neurofibrillary tangle formation and
      amyloid beta deposition associated with apolipoprotein E epsilon 4 homozygosity.
AB  - Niemann-Pick type C disease is a neurovisceral storage disorder. Neurofibrillary
      tangles similar to those in Alzheimer's disease have been reported in most
      juvenile/adult patients without amyloid beta protein (Abeta) deposits. Recently,
      we found deposits of Abeta in the form of diffuse plaques in three (31- and 32
      year-old sisters and a 37-year-old man) of nine Niemann-Pick type C disease
      patients, who presented with most severe tauopathy and with numerous
      neurofibrillary tangles. Abeta deposits were not detected in any of the control
      brains of patients younger than age 42 years. These three patients with Abeta
      deposit all were homozygotes of apolipoprotein E epsilon 4. Our study suggested
      that NPC1 gene mutations combined with homozygosity of apolipoprotein E epsilon 4
      alleles could manifest neuropathology similar to that of Alzheimer's disease.
      Investigation of these patients may provide an important clue for understanding
      the pathogenesis of Alzheimer's disease.

PMID- 12205650
TI  - Spontaneous mutations in the prion protein gene causing transmissible spongiform
      encephalopathy.
AB  - We analyzed the prion protein gene (PRNP) region in patients with transmissible
      spongiform encephalopathy associated with the PRNP D178N mutation. The results
      suggest that the D178N chromosomes had independent origins in each affected
      pedigree or apparently sporadic case. A de novo spontaneous PRNP mutation was
      observed. We provide evidence that hereditary and apparently sporadic
      transmissible spongiform encephalopathy cases associated with the D178N mutation
      result from multiple recurrent mutational events.

PMID- 12205651
TI  - Exclusion mapping of the genetic predisposition for cervical artery dissections
      by linkage analysis.
AB  - Skin biopsies from a patient with a dissection of the left internal carotid
      artery and from four of his children were analyzed by electron microscopy. The
      index patient and three children showed mild but regular electron microscopic
      connective tissue aberrations. They were considered as carriers of an unknown
      autosomal dominant mutation. Thirty-four candidate genes involved in the
      biosynthesis of the extracellular matrix were excluded by genetic linkage
      analysis as possible sites of a disease-causing mutation in this family
      (logarithm of odds [LOD]-score less than -2.0).

PMID- 12205652
TI  - LGI1 is mutated in familial temporal lobe epilepsy characterized by aphasic
      seizures.
AB  - Autosomal dominant lateral temporal lobe epilepsy previously has been linked to
      chromosome 10q22-q24, and recently mutations in the LGI1 gene (Leucine-rich gene,
      Glioma Inactivated) have been found in some autosomal dominant lateral temporal
      lobe epilepsy families. We have now identified a missense mutation affecting a
      conserved cysteine residue in the extracellular region of the LGI1 protein. The
      C46R mutation is associated with autosomal dominant lateral temporal lobe
      epilepsy in a large Norwegian family showing unusual clinical features like short
      lasting sensory aphasia and auditory symptoms.

PMID- 12205653
TI  - Impaired chemosensitivity to hypoxia is a marker of multiple system atrophy.
AB  - Sudden death is common in patients with multiple system atrophy (MSA). In its
      early stages, the cerebellar presentation MSA-C can be indistinguishable from
      idiopathic late-onset cerebellar ataxia. We studied the hypoxic ventilatory
      response in MSA-C and idiopathic late-onset cerebellar ataxia patients. Six
      patients with idiopathic late-onset cerebellar ataxia that later evolved to MSA
      had impaired hypoxic ventilatory response when minimal autonomic failure was
      still present, whereas for patients with unimpaired hypoxic ventilatory response
      their diagnosis remained idiopathic late-onset cerebellar ataxia. The
      demonstration of impaired hypoxic ventilatory response appears to be a good
      marker enabling earlier diagnosis of MSA in patients presenting with idiopathic
      late-onset cerebellar ataxia.

PMID- 12205654
TI  - Increased urine phenylethylamine after methylphenidate treatment in children with
      ADHD.
AB  - The urine levels of beta-phenylethylamine, 3-methoxy-4-hydroxyphenyl glycol,
      homovanillic acid, and 5-hydroxyindoleacetic acid were measured to clarify the
      neurochemical mechanism in attention deficit hyperactivity disorder. beta
      Phenylethylamine levels were significantly lower in attention deficit
      hyperactivity disorder individuals (n = 37) than in controls (n = 21). The 22
      children with attention deficit hyperactivity disorder were treated with
      methylphenidate, and they were further divided into methylphenidate responders (n
      = 18) and nonresponders (n = 4). beta-Phenylethylamine levels significantly
      increased after methylphenidate therapy in responders, whereas they did not
      increase in nonresponders.

PMID- 12205655
TI  - Leigh-like encephalopathy complicating Leber's hereditary optic neuropathy.
AB  - Leber's hereditary optic neuropathy is a mitochondrial disease caused by point
      mutations in mitochondrial DNA. It usually presents as severe bilateral visual
      loss in young adults. We report on a neurological disorder resembling Leigh
      syndrome, which complicated Leber's hereditary optic neuropathy in three
      unrelated male patients harboring mitochondrial DNA mutations at nucleotide
      positions 3460, 14459, and 14484, respectively. This Leigh-like encephalopathy
      appears to be associated with a much more severe outcome than isolated Leber's
      hereditary optic neuropathy.

PMID- 12205656
TI  - Clasmatodendrosis correlating with periventricular hyperintensity in mixed
      dementia.
AB  - We report a 79-year-old woman with possible Alzheimer's disease and confluent
      periventricular white matter hyperintensities on magnetic resonance imaging in
      whom postmortem analysis unexpectedly demonstrated no periventricular
      demyelination or cerebral arteriosclerosis. However, astrocytes in the
      periventricular white matter exhibited clasmatodendrosis, defined as cytoplasmic
      swelling and vacuolation of astroglia, with beading of their dendrites. This
      finding represents a previously unrecognized correlate of periventricular white
      matter hyperintensities. Ann Neurol 2002;52:378-381

PMID- 12205657
TI  - No evidence for individual blood-brain barrier phenylalanine transport to
      influence clinical outcome in typical phenylketonuria patients.

PMID- 12205659
TI  - Mild cognitive impairment and the cholinergic hypothesis: a very different take
      on recent data.

PMID- 12205662
TI  - Stem cell biology of the central nervous system.
AB  - Neural stem cells (NSCs) are multipotential progenitor cells that have self
      renewal activities. A single NSC is capable of generating various kinds of cells
      within the central nervous system (CNS), including neurons, astrocytes, and
      oligodendrocytes. Because of these characteristics, there is increasing interest
      in NSCs and neural progenitor cells from the aspects of both basic developmental
      biology and therapeutic applications to the damaged brain. This special issue,
      dedicated to understanding the nature of the NSCs present in the CNS, presents an
      introduction to several avenues of research that may lead to feasible strategies
      for manipulating cells in situ to treat the damaged brain. The topics covered by
      these studies include the extracellular factors and signal transduction cascades
      involved in the differentiation and maintenance of NSCs, the population dynamics
      and locations of NSCs in embryonic and adult brains, prospective identification
      and isolation of NSCs, the induction of NSCs to adopt particular neuronal
      phenotypes, and their transplantation into the damaged CNS.

PMID- 12205663
TI  - Radial glial cells as neuronal precursors: the next generation?

PMID- 12205664
TI  - Developmental regulation of the effects of fibroblast growth factor-2 and 1
      octanol on neuronogenesis: implications for a hypothesis relating to mitogen
      antimitogen opposition.
AB  - Neocortical neurons arise from a pseudostratified ventricular epithelium (PVE)
      that lies within the ventricular zone (VZ) at the margins of the embryonic
      cerebral ventricles. We examined the effects of fibroblast growth factor-2 (FGF
      2) and 1-octanol on cell output behavior of the PVE in explants of the embryonic
      mouse cerebral wall. FGF-2 is mitogenic and 1-octanol antimitogenic in the PVE.
      Whereas all postmitotic cells migrate out of the VZ in vivo, in the explants some
      postmitotic cells remain within the VZ. We refer to these cells as the
      indeterminate or I fraction, because they neither exit from the VZ nor reenter S
      phase as part of the proliferative (P) fraction. They are considered to be either
      in an extremely prolonged G(1) phase, unable to pass the G(1)/S transition, or in
      the G(0) state. The I fate choice is modulated by both FGF-2 and 1-octanol. FGF-2
      decreased the I fraction and increased the P fraction. In contrast, 1-octanol
      increased the I fraction and nearly eliminated the P fraction. The effects of FGF
      2 and 1-octanol were developmentally regulated, in that they were observed in the
      developmentally advanced lateral region of the cerebral wall but not in the
      medial region.

PMID- 12205665
TI  - Neurons tend to stop migration and differentiate along the cortical internal
      plexiform zones in the Reelin signal-deficient mice.
AB  - The Reelin molecule plays a fundamental role in corticogenesis. After Reelin
      binds to its receptors, the Reelin signal is transduced through tyrosine
      phosphorylation of the intracellular adaptor protein disabled 1 (Dab1). The
      reelin-gene-deficient mouse, reeler, and Dab1-deficient mouse, yotari, show
      disrupted positioning of neurons. Several molecules have been identified recently
      as being involved in Reelin signaling, however, the biological function of Reelin
      during cortical plate development was still unknown. We observed the migrating
      behavior of neurons during development in Reelin-signal-deficient mice. To
      visualize the migrating neurons directly, we introduced green fluorescent protein
      (GFP)-expression vectors into the ventricular zone with an in utero
      electroporation system and allowed the embryos to develop in utero until they
      were analyzed. The result showed that the migrating cells in the mutants were
      morphologically indistinguishable from those of normal mice. At the stage when
      the GFP-expressing cells reached the marginal zone near the pial surface and
      began dendrite formation in normal mice, the GFP-positive cells were found at
      various deeper positions in the mutant cortex. They had the morphology of
      migrating cells extending leading processes toward the pial surface. By contrast,
      in the mutants these cells tended to stop migration along the borders of the
      internal plexiform zone, the irregular structure consisting mainly of dendrites
      in the mutant cortex. Postnatally, these neurons began to develop dendrites later
      than the cells in the normal cortex. During this process, some neurons above the
      internal plexiform zone extended and developed dendrites in the opposite
      direction into the internal plexiform zone. These results suggest that the
      abnormal positioning of neurons in the Reelin-signal-deficient mice is caused, at
      least in part, by abnormal formation of the internal plexiform zone in the mutant
      cortex.

PMID- 12205666
TI  - Size distribution of retrovirally marked lineages matches prediction from
      population measurements of cell cycle behavior.
AB  - Mechanisms that regulate neuron production in the developing mouse neocortex were
      examined by using a retroviral lineage marking method to determine the sizes of
      the lineages remaining in the proliferating population of the ventricular zone
      during the period of neuron production. The distribution of clade sizes obtained
      experimentally in four different injection-survival paradigms (E11-E13, E11-E14,
      E11-E15, and E12-E15) from a total of over 500 labeled lineages was compared with
      that obtained from three models in which the average behavior of the
      proliferating population [i.e., the proportion of cells remaining in the
      proliferative population (P) vs. that exiting the proliferative population (Q)]
      was quantitatively related to lineage size distribution. In model 1, different
      proportions of asymmetric, symmetric terminal, and symmetric nonterminal cell
      divisions coexisted during the entire developmental period. In model 2, the
      developmental period was divided into two epochs: During the first, asymmetric
      and symmetric nonterminal cell divisions occurred, but, during the second,
      asymmetric and symmetric terminal cell divisions occurred. In model 3, the shifts
      in P and Q are accounted for by changes in the proportions of the two types of
      symmetric cell divisions without the inclusion of any asymmetric cell divisions.
      The results obtained from the retroviral experiments were well accounted for by
      model 1 but not by model 2 or 3. These findings demonstrate that: 1) asymmetric
      and both types of symmetric cell divisions coexist during the entire period of
      neurogenesis in the mouse, 2) neuron production is regulated in the proliferative
      population by the independent decisions of the two daughter cells to reenter S
      phase, and 3) neurons are produced by both asymmetric and symmetric terminal cell
      divisions. In addition, the findings mean that cell death and/or tangential
      movements of cells in the proliferative population occur at only a low rate and
      that there are no proliferating lineages "reserved" to make particular laminae or
      cell types.

PMID- 12205667
TI  - Adult neurogenesis and neural stem cells of the central nervous system in
      mammals.

PMID- 12205668
TI  - Differential expression of Musashi1 and nestin in the adult rat hippocampus after
      ischemia.
AB  - Both nestin and the neural RNA-binding protein Musashi1 (Msi1) are expressed in
      neural stem cells in the subventricular zone. Neurogenesis in the hippocampus has
      received much attention, so we evaluated the expression of Msi1 and nestin in the
      adult rat hippocampus after transient forebrain ischemia. Both Msi1 and nestin
      were induced in the reactive astrocytes after ischemia, especially in the CA1
      region, until 35 days after ischemia. Induction of both molecules suggested that
      reactive astrocytes might have immature characteristics. In the subgranular zone
      (SGZ) of the hippocampal dentate gyrus, Msi1-positive cells formed clusters after
      ischemia. These cells were labeled by bromodeoxyuridine (BrdU) but did not
      express glial fibrillary acidic protein. In contrast, very few nestin-positive
      cells were labeled by BrdU. Our results suggest that neuronal progenitor cells in
      the SGZ expressed Msi1 but not nestin.

PMID- 12205669
TI  - Amphiregulin is a mitogen for adult neural stem cells.
AB  - Neurons are continuously generated from stem cells in the hippocampus and along
      the lateral ventricles in the adult brain. Neural stem cells can be propagated in
      vitro in the presence of epidermal growth factor (EGF) or fibroblast growth
      factor-2. We report here that amphiregulin, a growth factor related to EGF, is a
      mitogen for adult mouse neural stem cells in vitro and displays potency similar
      to that of EGF. Neural stem cell cultures can be initiated and the cells
      propagated as efficiently in the presence of amphiregulin only as with EGF.
      Furthermore, we show that amphiregulin is expressed in the choroid plexus of the
      ventricular system and in the hippocampus in the adult brain, suggesting that
      amphiregulin may participate in the regulation of neural stem cell proliferation
      and neurogenesis in the adult brain.

PMID- 12205670
TI  - Growth factor treatment promotes mobilization of young but not aged adult
      subventricular zone precursors in response to demyelination.
AB  - Precursor cells of the adult mouse subventricular zone (SVZ) are mobilized and
      recruited by a lysolecithin (LPC)-induced demyelination of the corpus callosum.
      Because age decreases the proliferation of the SVZ neural precursors as well as
      the potential for myelin repair of the adult central nervous system, we have
      compared the ability of young and aged adult neural precursors to respond to LPC
      induced demyelination. With age, the SVZ cells lost their capacity to proliferate
      and to be recruited by the lesion. Whereas a single injection of fibroblast
      growth factor-2 or transforming growth factor-alpha stimulated the proliferation
      of SVZ and rostral migratory stream precursors in both groups of animals after
      demyelination, they favored recruitment at the lesion in young mice but not in
      aged ones. In vitro experiments using neurospheres derived from young and aged
      animals indicated that both populations have the same migratory performances. Our
      in vivo data thus suggest that aged neural precursors may loose their intrinsic
      capacities to respond to demyelination-induced signals. Alternatively, their
      function may be altered by modification of the aged extracellular environment.

PMID- 12205671
TI  - Hippocampal adult neurogenesis occurs in a microenvironment provided by PSA-NCAM
      expressing immature neurons.
AB  - Neurons continue to be generated in the adult hippocampus. In the present study,
      the early developmental processes of newly generated neurons in the adult rat
      hippocampus were examined by confocal laser scanning microscopy using a
      combination of bromodeoxyuridine (BrdU) labeling and immunohistochemistry for
      highly polysialylated neural cell adhesion molecule (PSA-NCAM) and NeuroD, which
      are markers for immature neurons, and glial fibrillary acidic protein (GFAP).
      Rats were injected with BrdU and 2 hours, 1, 3, and 7 days after the injection,
      the hippocampus was processed for immunohistochemistry. One day after the
      injection, BrdU-labeled cells were found frequently in clusters consisting of
      dividing cells, putative undifferentiated cells, NeuroD-positive differentiated
      neurons, and GFAP-positive astrocytes. Three days later, BrdU-labeled cells were
      loosely aggregated and BrdU-positive fragmented nuclei were sometimes observed,
      suggesting that apoptosis occurred in the clusters. These BrdU-labeled nuclei
      were frequently associated in various ways with the processes of immature PSA
      positive granule cells. They are positioned along PSA-positive apical and basal
      dendrites or surrounded by these processes. By 7 days after the injection, the
      number of the clusters was reduced and the BrdU-labeled cells had developed
      dendrites. These cell-to-cell associations support the hypothesis that the
      clustering and a microenvironment provided by the PSA-expressing immature neurons
      contribute to the early developmental events of adult neurogenesis, such as
      proliferation, differentiation, apoptosis, and neurophilic migration in the adult
      hippocampus.

PMID- 12205672
TI  - Nestin enhancer requirements for expression in normal and injured adult CNS.
AB  - The nestin gene is expressed in many CNS stem/progenitor cells, both in the
      embryo and the adult, and nestin is used commonly as a marker for these cells. In
      this report we analyze nestin enhancer requirements in the adult CNS, using
      transgenic mice carrying reporter genes linked to three different nestin enhancer
      constructs: the genomic rat nestin gene and 5 kb of upstream nestin sequence
      (NesPlacZ/3), 636 bp of the rat nestin second intron (E/nestin:EGFP), and a
      corresponding 714 bp region from the human second intron (Nes714tk/lacZ).
      NesPlacZ/3 and E/nestin:EGFP mice showed reporter gene expression in stem cell
      containing regions of brain and spinal cord during normal conditions. NesPlacZ/3
      and E/nestin:EGFP mice showed increased expression in spinal cord after injury
      and NesPlacZ/3 mice displayed elevated expression in the periventricular area of
      the brain after injury, which was not the case for the E/nestin:EGFP mice. In
      contrast, no expression in adult CNS in vivo was seen in the Nes714tk/lacZ mice
      carrying the human enhancer, neither during normal conditions nor after injury.
      The Nes714 tk/lacZ mice, however, expressed the reporter gene in reactive
      astrocytes and CNS stem cells cultured ex vivo. Collectively, this suggests a
      species difference for the nestin enhancer function in adult CNS and that
      elements outside the second intron enhancer are required for the full injury
      response in vivo.

PMID- 12205673
TI  - Intrinsic and extrinsic regulation of the proliferation and differentiation of
      cells in the rodent rostral migratory stream.
AB  - An overriding principle of development is that neurons become permanently
      postmitotic once they initiate differentiation. Work in our laboratory, however,
      has provided evidence for a population of progenitor cells in mammalian forebrain
      that express properties of differentiated neurons, even though they continue to
      divide. These neuronal progenitor cells are situated in the rostral migratory
      stream (RMS), which extends from a specialized portion of the subventricular zone
      surrounding the anterior tip of the lateral ventricle, referred to as the SVZa,
      to the middle of the olfactory bulb. As SVZa-derived cells migrate to the
      olfactory bulb, they undergo cell division, and they never deviate from the RMS.
      Once they reach their final destinations, they become terminally postmitotic
      interneurons. This Mini-Review concerns findings from our recent experiments
      designed to reveal the intrinsic and extrinsic mechanisms governing the
      proliferation and differentiation of the unique SVZa neuronal progenitor cells.
      We have investigated the role(s) of cell cycle regulatory proteins, in
      particular, the cell cycle inhibitor p19(INK4d), in the control of SVZa cell
      proliferation. Several studies have indicated that cells withdraw from the cell
      cycle once they express p19(INK4d). To begin to investigate whether p19(INK4d)(+)
      SVZa-derived cells are postmitotic, we analyzed the pattern of p19(INK4d)
      expression by the cells of the RMS. A pronounced gradient of p19(INK4d)
      expression was demonstrated; progressively more cells are p19(INK4d)
      immunoreactive as the olfactory bulb is approached. In addition, the capacity of
      p19(INK4d)(+) cells to incorporate bromodeoxyuridine was investigated. From the
      results of these studies, we conclude that SVZa cells in the RMS can successively
      down-regulate their expression of p19(INK4d) as they migrate and that they
      repeatedly exit and reenter the cell cycle while en route to the olfactory bulb.
      These studies led us to investigate whether bone morphogenetic proteins (BMPs)
      are involved in the regulation of SVZa cell proliferation and p19(INK4d)
      expression, because, elsewhere in the CNS, BMPs modulate cell proliferation and
      influence cell fate decisions. To determine the effects of BMP signaling on SVZa
      cell proliferation and differentiation, we altered the expression of the BMP
      receptor Ia (BMPR-Ia) using retrovirally mediated gene transfer. The cells in the
      SVZa encoding the wild-type BMPR-Ia exit the cell cycle and do not appear to
      migrate through the RMS. Conversely, both within the SVZa and along the RMS, the
      majority of SVZa-derived cells encoding a dominant-negative BMPR-Ia gene do not
      express p19(INK4d). These findings indicate that p19(INK4d) expression is
      suppressed when BMP signaling is inhibited. Furthermore, SVZa-derived cells with
      both augmented and inhibited BMP signaling retain their neuronal commitment.
      Collectively, these studies have revealed that SVZa cell proliferation and
      differentiation is under the control of several interacting intrinsic and
      extrinsic factors.

PMID- 12205674
TI  - Msx2 and p21(CIP1/WAF1) mediate the proapoptotic effects of bone morphogenetic
      protein-4 on ventricular zone progenitor cells.
AB  - Treatment of cultured ventricular zone (VZ) progenitor cells with bone
      morphogenetic protein-4 (BMP4) promoted cell death in a dose-dependent manner. VZ
      progenitor cells became progressively more resistant to the proapoptotic effects
      of BMP4 between E10 and E16, and, by E18 and thereafter, BMP4 treatment no longer
      led to progenitor cell death. BMP4 treatment of E13 progenitor cells promoted
      expression of msx2 and p21(CIP1/WAF1) (p21) and inhibition of expression of
      either gene prevented BMP4-mediated apoptosis. Treatment of E18 cells with BMP4
      failed to induce apoptosis but still induced expression of low levels of msx2 and
      p21. Knockout of bax significantly reduced but did not prevent BMP4-mediated
      death of E13 murine progenitor cells. These observations indicate that msx2 and
      p21 mediate the proapoptotic effects of BMP4 on VZ progenitor cells and that each
      gene is necessary but insufficient to promote apoptosis.

PMID- 12205675
TI  - Selective specification of CNS stem cells into oligodendroglial or neuronal cell
      lineage: cell culture and transplant studies.
AB  - Neural stem cells (NSCs) were isolated from embryonic day 16 Sprague-Dawley rats
      and cultured in a novel serum-free stem cell medium that selected for the growth
      of NSCs and against the growth of GFAP(+) cells (astrocytes). NSCs maintained in
      culture for extended periods of time retained immunoreactivity for both nestin
      and PSA-NCAM, two markers characteristic of the stem cell phenotype. Moreover,
      using an oligodendrocyte (OL) specification medium, NSCs differentiated into OL
      as evidenced by their morphology and expression of multiple
      oligodendrocyte/myelin-specific markers. In addition, NSCs are capable of
      acquiring a neuronal phenotype as evidenced by expressing neuronal markers, such
      as neurofilament (NF) and NeuN when cultured in a defined medium for neurons
      indicating that these cells are also a good source of neuroblasts, which could be
      used to replace neuronal populations in the brain. We also showed successful
      propagation and differentiation of NSCs into OL after cryostorage, allowing for
      the later use of stored NSCs. The long-term goal of culturing NSCs and committed
      oligodendrocyte progenitors (OLP) is to obtain homogeneous populations for
      transplantation with the goal of remyelinating the myelin-deficient CNS. Our
      preliminary experiments carried out on normal and myelin deficient rats
      demonstrate that these cells survive and migrate extensively in both types of
      hosts. NSCs grafted as such, as well as cells derived from NSCs exposed to
      selective specification before grafting, are able to differentiate within the
      host brain. As expected, NSCs are capable of giving rise to astrocytes in a
      medium favoring this phenotype.

PMID- 12205676
TI  - Differentiation of proliferated NG2-positive glial progenitor cells in a
      remyelinating lesion.
AB  - Cells that express the NG2 proteoglycan (NG2+ cells) constitute a large cell
      population in the adult mammalian central nervous system (CNS). They give rise to
      mature oligodendrocytes in culture and are thus considered to be oligodendrocyte
      progenitor cells (OPCs). They proliferate in response to a variety of insults to
      the CNS, but their ability to differentiate into oligodendrocytes in vivo has not
      been established. We used bromodeoxyuridine (BrdU) to trace the fate of NG2+
      cells that proliferated in response to a chemically induced demyelinating lesion
      in the adult rat spinal cord. Cells that were proliferating 24 hr after lesioning
      were labeled by a single injection of BrdU, and their antigenic phenotype was
      examined at various times up to 28 days post-lesioning (28 dpl). Initially, at 2
      dpl, NG2+/BrdU+ cells were found almost exclusively at the periphery of the
      lesion. At 7 dpl, the number of NG2+/BrdU+ cells increased in the lesion center
      and decreased from the surrounding areas. The number of NG2+/BrdU+ cells inside
      the lesion further decreased with time, concomitant with progression of
      remyelination and appearance of BrdU+ mature oligodendrocytes. Double labeling
      with (3)H-thymidine and BrdU combined with NG2 immunohistochemistry showed that
      some NG2+ cells in the lesion had undergone at least two rounds of cell division.
      These observations strongly suggest that NG2+/BrdU+ cells that appeared in
      response to the demyelinating insult gave rise to mature remyelinating
      oligodendrocytes, providing an in vivo evidence for the differentiation of NG2+
      cells into oligodendrocytes.

PMID- 12205677
TI  - Flow cytometric analysis of neural stem cells in the developing and adult mouse
      brain.
AB  - Despite recent progress in the neural stem cell biology, their cellular
      characteristics have not been described well. We investigated various
      characteristics of neural stem cells (NSCs) in vivo during CNS development, using
      FACS to identify the NSCs. We first examined stage-dependent changes in the
      physical parameters, using forward scatter (FSC) and side scatter (SSC) profiles,
      of NSCs from the developing striatum, where they appear to be active throughout
      the life of mammals. NSCs were divided into several fractions according to their
      FSC/SSC profile. With development, their number decreased in the FSC(high)
      fractions but increased in the FSC(low)/SSC(high) fraction, whereas NSCs were
      significantly concentrated in the fraction containing the largest cells (about 20
      microm in diameter) at any stage, which were mostly the cells with the highest
      nestin-enhancer activity. Furthermore, we demonstrated that, at all stages
      examined, the "side population" (SP), defined as the Hoechst 33342 low/negative
      fraction, which is known to be a stem cell-enriched population in bone marrow,
      was also enriched for Notch1-positive immature neural cells (about 60%) from the
      developing striatum. However, these immature SP cells were not detected in the
      large-cell fraction, however, but were concentrated instead in the FSC(low/mid)
      fractions. FACS analysis showed that SP cells from adults were included to some
      extent in the CD24(low)/PNA(low) fraction, where NSCs were greatly concentrated.
      Collectively, the characteristics of NSCs were not uniform and changed
      developmentally.

PMID- 12205678
TI  - Notch signaling promotes astrogliogenesis via direct CSL-mediated glial gene
      activation.
AB  - In the developing central nervous system (CNS), Notch signaling preserves
      progenitor pools and inhibits neurogenesis and oligodendroglial differentiation.
      It has recently been postulated that Notch instructively drives astrocyte
      differentiation. Whether the role of Notch signaling in promoting astroglial
      differentiation is permissive or instructive has been debated. We report here
      that the astrogliogenic role of Notch is in part mediated by direct binding of
      the Notch intracellular domain to the CSL DNA binding protein, forming a
      transcriptional activation complex onto the astrocyte marker gene, glial
      fibrillary acidic protein (GFAP). In addition, we found that, in CSL-/- neural
      stem cell cultures, astrocyte differentiation was delayed but continued at a
      normal rate once initiated, suggesting that CSL is involved in regulating the
      onset of astrogliogenesis. Importantly, although the classical CSL-dependent
      Notch signaling pathway is intact and able to activate the Notch canonical target
      promoter during the neurogenic phase, it is unable to activate the GFAP promoter
      during neurogenesis. Therefore, the effect of Notch signaling on target genes is
      influenced by cellular context in regulation of neurogenesis and gliogenesis.

PMID- 12205679
TI  - Visualization of cell cycling by an improvement in slice culture methods.
AB  - Slice culture combined with the use of fluorescent dyes and/or the introduction
      of fluorescent protein genes provides live and three-dimensional information on
      cytogenetic and histogenetic events at the level of the individual cell. Using
      slices prepared from midembryonic mouse cerebral wall tissue upon which fine DiI
      crystals were placed on the pial or ventricular surface, we recently found that
      dividing progenitor cells do not lose their pia-connected (basal) processes and
      that the processes are inherited by daughter cells, including neurons (Miyata et
      al. [2001] Neuron 31:727-741). To understand more fully the biological
      significance of this inheritance process, the fate of each daughter cell should
      be monitored over a culture period extended long enough to allow a neuron to
      migrate up to the cortex or for a progenitor to proceed to the next round of
      division. Exposure of slices to 40%, instead of 20%, O(2) significantly improved
      their overall thickening, cell production, and layer formation and also provided
      better spatial resolution by preventing the loss of transparency that accompanies
      cell death.

PMID- 12205680
TI  - Evaluation of in vitro proliferative activity of human fetal neural
      stem/progenitor cells using indirect measurements of viable cells based on
      cellular metabolic activity.
AB  - To scale up human neural stem/progenitor cell (NSPC) cultures for clinical use,
      we need to know how long these cells can live ex vivo without losing their
      ability to proliferate and differentiate; thus, a convenient method is needed to
      estimate the proliferative activity of human NSPCs grown in neurosphere cultures,
      as direct cell counting is laborious and potentially inaccurate. Here, we
      isolated NSPCs from human fetal forebrain and prepared neurosphere cultures. We
      determined the number of viable cells and estimated their proliferative activity
      in long-term culture using two methods that measure viable cell numbers
      indirectly, based on their metabolic activity: the WST-8 assay, in which a
      formazan dye is produced upon reduction of the water-soluble tetrazolium salt WST
      8 by dehydrogenase activity, and the ATP assay, which measures the ATP content of
      the total cell plasma. We compared the results of these assays with the
      proliferative activity estimated by DNA synthesis using the 5-bromo-2'
      deoxyuridine incorporation assay. We found the numbers of viable human NSPCs to
      be directly proportional to the metabolic reaction products obtained in the WST-8
      and ATP assays. Both methods yielded identical cell growth curves, showing an
      exponentially proliferative phase and a change in the population doubling time in
      long-term culture. They also showed that human NSPCs could be expanded for up to
      200 days ex vivo without losing their ability to proliferate and differentiate.
      Our findings indicated that indirect measurements of viable cells based on
      metabolic activity, especially the ATP assay, are very effective and reproducible
      ways to determine the numbers of viable human NSPCs in intact neurospheres.

PMID- 12205681
TI  - Neural cells derived from adult bone marrow and umbilical cord blood.
AB  - Under experimental conditions, tissue-specific stem cells have been shown to give
      rise to cell lineages not normally found in the organ or tissue of residence.
      Neural stem cells from fetal brain have been shown to give rise to blood cell
      lines and conversely, bone marrow stromal cells have been reported to generate
      skeletal and cardiac muscle, oval hepatocytes, as well as glia and neuron-like
      cells. This article reviews studies in which cells from postnatal bone marrow or
      umbilical cord blood were induced to proliferate and differentiate into glia and
      neurons, cellular lineages that are not their normal destiny. The review
      encompasses in vitro and in vivo studies with focus on experimental variables,
      such as the source and characterization of cells, cell-tracking methods, and
      markers of neural differentiation. The existence of stem/progenitor cells with
      previously unappreciated proliferation and differentiation potential in postnatal
      bone marrow and in umbilical cord blood opens up the possibility of using stem
      cells found in these tissues to treat degenerative, post-traumatic and hereditary
      diseases of the central nervous system.

PMID- 12205682
TI  - Neuronal differentiation of stem cells isolated from adult muscle.
AB  - Lineage uncommitted pluripotent stem cells reside in the connective tissue of
      skeletal muscle. The present study was carried out with pluripotent stem cells
      (PPSCs) isolated from 6-month old rat muscle. Before differentiation, these cells
      were vimentin+, CD90+, CD45-, and varied in their expression of CD34. The PPSCs
      were expanded as non-adherent aggregates under similar conditions to those used
      to generate neurospheres from embryonic or neural stem cells. The PPSC-derived
      neurospheres were positive for nestin, an early marker present in neuronal
      precursors, and expressed the two alternative mRNA forms of the neuroectodermal
      marker Pax-6, as well as mRNA for Oct-4, a gene related to the pluripotentiality
      of stem cells. To confirm their neural potential, PPSC-derived neurospheres were
      plated on coated coverslips under varying conditions: Neurobasal medium with N2
      or B27, and either NT3 or BDNF. After 4-6 days the cells expressed neuronal
      (Tuj1+, NF68), astrocytic (GFAP) and oligodendrocytic (MOSP+, MBP+) markers, both
      by immunocytochemistry and RT-PCR. In addition, PPSCs were cultured as monolayers
      under adherent conditions, exposed to growth factors and defined differentiating
      conditions for 5 hr, and subsequently kept for 2 days in a maturation medium. At
      this point they gave rise to a mixed population of early neural progenitors
      (Nestin+ or NG2+), immature and mature neurons (Tuj1+ and NF145+) and myelin
      producing oligodendrocytes (CNPase + and MOSP+). Our study shows that PPSCs
      present in adult muscle can overcome germ lineage restrictions and express the
      molecular characteristics of brain cells. Therefore, PPSCs isolated from adult
      muscle could provide a novel source for autologous cell replacement in
      neurodegenerative and demyelinating diseases.

PMID- 12205683
TI  - Adult bone marrow stromal stem cells express germline, ectodermal, endodermal,
      and mesodermal genes prior to neurogenesis.
AB  - Bone marrow stromal stem cells (MSCs) normally differentiate into mesenchymal
      derivatives but recently have also been converted into neurons, classical
      ectodermal cells. To begin defining underlying mechanisms, we extended our
      characterization of MSCs and the differentiated neurons. In addition to expected
      mesodermal mRNAs, populations and clonal lines of MSCs expressed germinal,
      endodermal, and ectodermal genes. Thus, the MSCs are apparently
      "multidifferentiated" in addition to being multipotent. Conversely, the
      differentiating neurons derived from populations and clonal lines of MSCs
      expressed the specific markers beta-III tubulin, tau, neurofilament-M, TOAD-64,
      and synaptophysin de novo. The transmitter enzymes tyrosine hydroxylase and
      choline acetyltransferase were localized to neuronal subpopulations. Our
      observations suggest that MSCs are already multidifferentiated and that neural
      differentiation comprises quantitative modulation of gene expression rather than
      simple on-off switching of neural-specific genes.

PMID- 12205684
TI  - Tau EGFP embryonic stem cells: an efficient tool for neuronal lineage selection
      and transplantation.
AB  - Pluripotency and the capacity for continuous self-renewal make embryonic stem
      (ES) cells an attractive donor source for cell-replacement strategies. A key
      prerequisite for a therapeutic application of ES cells is the generation of
      defined somatic cell populations. Here we demonstrate that a targeted insertion
      of the EGFP gene into the tau locus permits efficient fluorescence-activated cell
      sorting (FACS)-based lineage selection of ES cell-derived neurons. After in vitro
      differentiation of heterozygous tau EGFP ES cells into multipotent neural
      precursors, EGFP is selectively induced in postmitotic neurons of various
      neurotransmitter phenotypes. By using FACS, ES cell-derived neurons can be
      enriched to purities of more than 90%. Because neuron-specific EGFP fluorescence
      is also observed upon transplantation of ES cell-derived neural precursors, the
      tau EGFP mutant represents a useful tool for the in vivo analysis of grafted ES
      cell-derived neurons.

PMID- 12205685
TI  - Transplantation of in vitro-expanded fetal neural progenitor cells results in
      neurogenesis and functional recovery after spinal cord contusion injury in adult
      rats.
AB  - Neural progenitor cells, including neural stem cells, are a potential expandable
      source of graft material for transplantation aimed at repairing the damaged CNS.
      Here we present the first evidence that in vitro-expanded fetus-derived
      neurosphere cells were able to generate neurons in vivo and improve motor
      function upon transplantation into an adult rat spinal-cord-contusion injury
      model. As the source of graft material, we used a neural stem cell-enriched
      population that was derived from rat embryonic spinal cord (E14.5) and expanded
      in vitro by neurosphere formation. Nine days after contusion injury, these
      neurosphere cells were transplanted into adult rat spinal cord at the injury
      site. Histological analysis 5 weeks after the transplantation showed that mitotic
      neurogenesis occurred from the transplanted donor progenitor cells within the
      adult rat spinal cord, a nonneurogenic region; that these donor-derived neurons
      extended their processes into the host tissues; and that the neurites formed
      synaptic structures. Furthermore, analysis of motor behavior using a skilled
      reaching task indicated that the treated rats showed functional recovery. These
      results indicate that in vitro-expanded neurosphere cells derived from the fetal
      spinal cord are a potential source for transplantable material for treatment of
      spinal cord injury.

PMID- 12205686
TI  - Optimal conditions for in vivo induction of dopaminergic neurons from embryonic
      stem cells through stromal cell-derived inducing activity.
AB  - A method of inducing dopamine (DA) neurons from mouse embryonic stem (ES) cells
      by stromal cell-derived inducing activity (SDIA) was previously reported. When
      transplanted, SDIA-induced DA neurons integrate into the mouse striatum and
      remain positive for tyrosine hydroxylase (TH) expression. In the present study,
      to optimize the transplantation efficiency, we treated mouse ES cells with SDIA
      for various numbers of days (8-14 days). SDIA-treated ES cell colonies were
      isolated by papain treatment and then grafted into the 6-hydroxydopamine (6-OHDA)
      lesioned mouse striatum. The ratio of the number of surviving TH-positive cells
      to the total number of grafted cells was highest when ES cells were treated with
      SDIA for 12 days before transplantation. This ratio revealed that grafting cell
      colonies was more efficient for obtaining TH-positive cells in vivo than grafting
      cell suspensions. When we grafted a cell suspension of 2 x 10(5), 2 x 10(4), or 2
      x 10(3) cells into the 6-OHDA-lesioned mouse striatum, we observed only a few
      surviving TH-positive cells. In conclusion, inducing DA neurons from mouse ES
      cells by SDIA for 12 days and grafting cell colonies into mouse striatum was the
      most effective method for the survival of TH-positive neurons in vivo.

PMID- 12205687
TI  - Immunohistochemical and electron microscopic study of invasion and
      differentiation in spinal cord lesion of neural stem cells grafted through
      cerebrospinal fluid in rat.
AB  - Neurospheres were obtained by culturing hippocampal cells from transgenic rat
      fetuses (E16) expressing green fluorescent protein (GFP). The neurosphere cells
      were injected into the cerebrospinal fluid (CSF) through the 4th ventricle of
      young rats (4 weeks old) that had been given a contusion injury at T8-9 of the
      spinal cord. The injected neural stem cells were transported through the CSF to
      the spinal cord, attached to the pial surface at the lesion, and invaded
      extensively into the spinal cord tissue as well as into the nerve roots. The
      grafted stem cells survived well in the host spinal cord for as long as 8 months
      after transplantation. Immunohistochemical study showed that many grafted stem
      cells had differentiated into astrocytes at 1-4 months, and some into
      oligodendrocytes at 8 months postoperatively. Immunoelectron microscopy showed
      that the grafted stem cells were well integrated into the host tissue, extending
      their processes around nerve fibers in the same manner as astrocytes. In
      addition, grafted stem cells within nerve roots closely surrounded myelinated
      fibers or were integrated into unmyelinated fiber bundles; those associated with
      myelinated fibers formed basal laminae on their free surface, whereas those
      associated with unmyelinated fibers were directly attached to axons and Schwann
      cells, indicating that grafted stem cells behaved like Schwann cells in the nerve
      roots.

PMID- 12205688
TI  - Neuroprotective and restorative effects of intrastriatal grafting of encapsulated
      GDNF-producing cells in a rat model of Parkinson's disease.
AB  - Glial cell line-derived neurotrophic factor (GDNF) has been shown to possess
      potent neurotrophic effects on dopaminergic (DA) neurons. We attempted the
      transplantation of encapsulated GDNF-producing cells to generate a stable supply
      of GDNF in the brain to promote neuroprotective and restorative effects for DA
      neurons. We established baby hamster kidney (BHK) cells and introduced GDNF cDNA
      to produce human GDNF (BHK-GDNF). These BHK-GDNF cells, or nontransfected BHK
      cells (BHK-Control), were encapsulated into hollow fibers, and the polymer
      encapsulated cells were unilaterally implanted into the striatum of adult rats,
      either before or after the administration of 6-hydroxydopamine into the same
      striatum. The encapsulated BHK-GDNF cells produced GDNF continuously in the
      striatum for up to 6 months. The rats that received a BHK-GDNF capsule showed a
      significant decrease in rotational behaviour compared to those that received a
      BHK-control capsule. Preservation of the nigrostriatal pathway was significantly
      greater in those that received a BHK-GDNF capsule than in those that received a
      BHK-control capsule. This indicates that encapsulated GDNF-producing cells can
      supply GDNF in a stable fashion and have protective and restorative effects on
      host DA neurons. Our results support a role for this grafting technique in the
      treatment of Parkinson's disease.

PMID- 12205689
TI  - Neurospheres modified to produce glial cell line-derived neurotrophic factor
      increase the survival of transplanted dopamine neurons.
AB  - Glial cell line-derived neurotrophic factor (GDNF) has been shown to increase the
      survival of dopamine neurons in a variety of in vitro and in vivo model systems.
      Therefore, it constitutes an important therapeutic protein with the potential to
      ameliorate dopamine neuronal degeneration in Parkinson's disease or to support
      dopamine neuronal replacement strategies. However, biophysical and practical
      considerations present obstacles for the direct delivery of the GDNF protein to
      CNS neurons. Here we show that rodent neural precursor cells isolated and
      expanded in culture as neurospheres (NS) can be genetically modified to express
      green fluorescent protein (GFP) or to release GDNF using lentiviral constructs.
      GDNF-NS increased the fibre outgrowth of primary embryonic dopamine neurons in
      cocultures, showing that the protein was released in biologically significant
      quantities. Furthermore, after transplantation into the 6-hydroxydopamine
      lesioned rat striatum, GDNF-NS significantly increased the survival of cografted
      primary dopamine neurons. However, this was not reflected in behavioural recovery
      in these animals. We found that, by 6 weeks, few cells expressed GDNF or GFP,
      suggesting either that transgene expression was down-regulated over time or that
      the cells died. This may explain the initial effects on dopamine neuronal
      survival within the graft but the lack of long-term effect on subsequent fibre
      outgrowth and behaviour. Providing sustained levels of neural precursor-mediated
      transgene expression can be achieved following transplantation in the future;
      this approach may prove beneficial as an alternative therapeutic strategy in the
      cell-based management of Parkinson's disease.

PMID- 12205690
TI  - Progenitor cells derived from the adult human subcortical white matter disperse
      and differentiate as oligodendrocytes within demyelinated lesions of the rat
      brain.
AB  - A distinct population of white matter progenitor cells (WMPCs), competent but not
      committed to generate oligodendrocytes, remains ubiquitous in the adult human
      subcortical white matter. These cells are present in both sexes and into
      senescence and may constitute as much as 4% of the cells of adult human capsular
      white matter. Transduction of adult human white matter dissociates with plasmids
      bearing early oligodendrocytic promoters driving fluorescent reporters permits
      the separation of these cells at high yield and purity, as does separation based
      on their expression of A2B5 immunoreactivity. Isolates of these cells survive
      xenograft to lysolecithin-demyelinated brain and migrate rapidly to infiltrate
      these lesions, without extending into normal white matter. Within several weeks,
      implanted progenitors mature as oligodendrocytes, and develop myelin-associated
      antigens. Lentiviral tagging with green fluorescent protein confirmed that A2B5
      sorted progenitors develop myelin basic protein expression within regions of
      demyelination and that they fail to migrate when implanted into normal brain.
      Adult human white matter progenitor cells can thus disperse widely through
      regions of experimental demyelination and are able to differentiate as
      myelinating oligodendrocytes. This being the case, they may constitute
      appropriate vectors for cell-based remyelination strategies.

PMID- 12205691
TI  - Engraftment of sorted/expanded human central nervous system stem cells from fetal
      brain.
AB  - Direct isolation of human central nervous system stem cells (CNS-SC) based on
      cell surface markers yields a highly purified stem cell population that can
      extensively expand in vitro and exhibit multilineage differentiation potential
      both in vitro and in vivo. The CNS-SC were isolated from fetal brain tissue using
      the cell surface markers CD133(+), CD34(-), CD45(-), and CD24(-/lo) (CD133(+)
      cells). Fluorescence-activated cell sorted (FACS) CD133(+) cells continue to
      expand exponentially as neurospheres while retaining multipotential
      differentiation capacity for >10 passages. CD133(-), CD34(-), and CD45(-) sorted
      cells (approximately 95% of total fetal brain tissue) fail to initiate
      neurospheres. Neurosphere cells transplanted into neonatal immunodeficient NOD
      SCID mice proliferated, migrated, and differentiated in a site-specific manner.
      However, it has been difficult to evaluate human cell engraftment, because many
      of the available monoclonal antibodies against neural cells (beta-tubulin III and
      glial fibrillary acidic protein) are not species specific. To trace the progeny
      of human cells after transplantation, CD133(+)-derived neurosphere cells were
      transduced with lentiviral vectors containing enhanced green fluorescent protein
      (eGFP) expressed downstream of the phosphoglycerate kinase promoter. After
      transduction, GFP(+) cells were enriched by FACS, expanded, and transplanted into
      the lateral ventricular space of neonatal immunodeficient NOD-SCID brain. The
      progeny of transplanted cells were detected by either GFP fluorescence or
      antibody against GFP. GFP(+) cells were present in the subventricular zone
      rostral migrating stream, olfactory bulb, and hippocampus as well as
      nonneurogenic sites, such as cerebellum, cerebral cortex, and striatum. Antibody
      against GFP revealed that some of the cells displayed differentiating dendrites
      and processes with neurons or glia cells. Thus, marking human CNS-SC with
      reporter genes introduced by lentiviral vectors is a useful tool with which to
      characterize migration and differentiation of human cells in this mouse
      transplantation model.

PMID- 12205692
TI  - Estimating a treatment effect in survival studies in which patients switch
      treatment.
AB  - For disease indications such as Acquired Immune Deficiency Syndrome (AIDS) and
      various cancers, randomization to a pure control treatment may be scientifically
      desirable but not ethically acceptable. Clinicians may insist that the
      experimental treatment be made available, at least as a rescue medication, for
      all patients in the control arm. A method for estimating a treatment effect in
      survival data from randomized clinical trials of this type is developed under an
      accelerated failure time model. This approach retains all patients in the groups
      to which they were randomized and is not based on an ad hoc subgroup analysis. By
      conditioning on having observed patient switch times, this method avoids the need
      to model patient switching patterns in the analysis. This new approach is
      evaluated using simulation studies, and is illustrated through analysing data
      from a Medical Research Council lung cancer trial.

PMID- 12205693
TI  - Inflation of type I error rate in two statistical tests for the detection of
      publication bias in meta-analyses with binary outcomes.
AB  - The use of meta-analysis to combine results of several trials is still increasing
      in the medical field. The validity of a meta-analysis may be affected by various
      sources of bias (for example, publication bias, language bias). Therefore, an
      analysis of bias should be an integral part of any systematic review. Statistical
      tests and graphical methods have been developed for this purpose. In this paper,
      two statistical tests for the detection of bias in meta-analysis were
      investigated in a simulation study. Binary outcome data, which are very common in
      medical applications, were considered and relative effect measures (odds ratios,
      relative risk) were used for pooling. Sample sizes were generated according to
      findings in a survey of eight German medical journals. Simulation results
      indicate an inflation of type I error rates for both tests when the data are
      sparse. Results get worse with increasing treatment effect and number of trials
      combined. Valid statistical tests for the detection of bias in meta-analysis with
      sparse data need to be developed.

PMID- 12205694
TI  - Minimax two-stage-designs with applications to tissue banking case-control
      studies.
AB  - 'Tissue banks' are created, at least in part, to help medical scientists learn
      about disease biology on the basis of samples provided by patients on treatment
      protocols that were competed years earlier. The bank inventory consists of
      precious non-renewable patient material (such as frozen diagnostic blood or bone
      marrow), which can be linked to both clinical data and long term follow-up
      information. Case-control studies, where cases represent clinical failures and
      controls clinical successes, are ideal for rapidly learning if a laboratory
      marker might have prognostic significance. While group sequential (multi-stage)
      methods are widely used in clinical trials, they have rarely been applied in case
      control studies. Further, unlike clinical trials where safety and efficiency may
      actually be in conflict, case-control studies can focus on efficiency. Hence,
      minimizing the expected sample size is a desirable goal in such a setting. Since
      the true effect size is never known, and since no prior distribution can be
      postulated for the effect size, we have opted for the minimax solution. A
      strategy is developed to determine amongst all two-stage designs with given type
      I and type II errors, the one for which the maximum expected sample size is
      minimized. The user is provided with simple tables, whereby one can determine
      everything necessary to conduct the study from the corresponding calculation for
      a single-stage design. A matched pair example is given where the suggested design
      can be modified, to obtain a superior 'two-plus' stage design. The basic idea is
      to conduct the first stage as planned, but use the estimate of variance to
      redesign the study, without using the estimate of effect size in the redesign.

PMID- 12205695
TI  - Bias in risk estimation: application to Down's syndrome screening.
AB  - In this paper we consider the bias associated with parametric estimation of a
      univariate or bivariate Gaussian density, and also the induced bias when these
      Gaussian densities are used to determine a likelihood ratio. Algebraic
      approximations are derived that accurately predict the relative biases obtained,
      verification being achieved by a simulation exercise. The expressions confirm
      that when estimating a univariate Gaussian density there are four Z-scores for
      which there is zero bias and that relative bias increases rapidly beyond two
      standard deviations from the mean. The results are then extended to determine
      approximate confidence intervals for both the true density and the likelihood
      ratio. A simulation exercise confirms that the derived 95 per cent confidence
      intervals have coverage that ranges from 94 to 97 per cent. The results are
      applied to a Down's syndrome screening programme where 95 per cent confidence
      intervals are established for a woman's posterior odds of carrying a Down's
      foetus. It is shown that patients with similar posterior odds can give rise to
      confidence intervals for their true posterior odds that have very different
      widths, thus emphasizing that not all risks are of equal quality.

PMID- 12205696
TI  - A multistate model for the genetic analysis of the ageing process.
AB  - In this paper a multivariate frailty model is suggested that can be used in the
      genetic analysis of the ageing process as a whole, simplified to consisting of
      the states 'healthy', 'disabled' and 'deceased'. The model allows us to evaluate
      simultaneously the relative magnitude of genetic and environmental influences on
      frailty variables corresponding to the period of good health and to the life
      span. The frailty variables can be interpreted as susceptibility to illness or
      death. The model can be applied to data on groups of related individuals (twins,
      siblings, a litter). One of the major advantages of this model is that it allows
      one to include groups of individuals where some or all members of the group are
      already deceased at the time of observation. The current health status of the
      living individuals and the exact life span of individuals who are already
      deceased is the only information necessary for the application of the model.
      Questions concerning the identifiability of the model based on current health
      status data and estimation strategies are discussed in the context of specifying
      the model for twins. Finally, the results of a sample analysis of twin data on
      prostate cancer are presented.

PMID- 12205697
TI  - Assessing the gain in diagnostic performance when combining two diagnostic tests.
AB  - Combining dichotomous (or dichotomized) results of two diagnostic tests will
      result in a trade-off in sensitivity and specificity of the combined test
      relative to the component tests. Because of this inherent trade-off, likelihood
      ratios provide a clinically relevant means of comparing the combined test with
      one of its components. The likelihood ratios depend on both sensitivity and
      specificity and hence take into account the trade-off between them. A graphical
      approach is used to assess whether the combined test is superior to a component
      test, or vice versa. Asymptotic standard errors are derived for comparing
      likelihood ratios when a paired study design is used. The trade-off in the
      expected number of additional true positive and false positive results (or true
      negative and false negative results) is used as the basis for deciding whether to
      use tests in combination when neither the combined nor a component test shows
      superior test performance based on their likelihood ratios. These methods are
      illustrated with an example that considers the combined use of Pap and HPV
      testing.

PMID- 12205698
TI  - Multivariate survival analysis with doubly-censored data: application to the
      assessment of Accutane treatment for fibrodysplasia ossificans progressiva.
AB  - Fibrodysplasia ossificans progressiva is a rare genetic disorder in which the
      joints of patients become disabled by the formation of heterotopic bone. Data are
      available on the status of 11 joints of each of 21 patients before, during and
      after treatment with Accutane. These are compared with data obtained by
      questionnaire from 40 untreated patients to determine the efficacy of the
      treatment. Both left- and right-censoring are present in each group, which,
      together with the multivariate nature of the data and the time-dependent
      treatment covariate, makes analysis difficult. We consider two alternative
      parametric models for incorporating within-subject dependence: a marginal model
      and a frailty model. Both analyses suggest that Accutane treatment is effective.
      We discuss and illustrate the differences between the two approaches. We also
      discuss the extent to which the conclusions are compromised by the observational
      nature of the study.

PMID- 12205699
TI  - Likelihood methods for measuring statistical evidence.
AB  - Focused on interpreting data as statistical evidence, the evidential paradigm
      uses likelihood ratios to measure the strength of statistical evidence. Under
      this paradigm, re-examination of accumulating evidence is encouraged because (i)
      the likelihood ratio, unlike a p-value, is unaffected by the number of
      examinations and (ii) the probability of observing strong misleading evidence is
      naturally low, even for study designs that re-examine the data with each new
      observation. Further, the controllable probabilities of observing misleading and
      weak evidence provide assurance that the study design is reliable without
      affecting the strength of statistical evidence in the data. This paper
      illustrates the ideas and methods associated with using likelihood ratios to
      measure statistical evidence. It contains a comprehensive introduction to the
      evidential paradigm, including an overview of how to quantify the probability of
      observing misleading evidence for various study designs. The University Group
      Diabetes Program (UGDP), a classic and still controversial multi-centred clinical
      trial, is used as an illustrative example. Some of the original UGDP results, and
      subsequent re-analyses, are presented for comparison purposes.

PMID- 12205700
TI  - Randomized consent designs for clinical trials: an update.

PMID- 12205705
TI  - Afferent input regulates the formation of distal dendritic branches.
AB  - During postembryonic development, the dendritic arbors of neurons grow to
      accommodate new incoming synaptic inputs. Our goal was to examine which features
      of dendritic architecture of postsynaptic interneurons are regulated by these
      synaptic inputs. To address this question, we took advantage of the cockroach
      cercal system where the morphology of the sensory giant interneurons (GIs) is
      uniquely identified and, therefore, amenable to quantitative analysis. We
      analyzed the three-dimensional architecture of chronically deafferented vs.
      normally developed dendritic trees of a specific identified GI, namely GI2. GI2
      shows five prominent dendrites, four of which were significantly altered after
      deafferentation. De-afferentation induced an average of 55% decrease in metric
      measures (number of branch points, total length, and total surface area) on the
      entire dendritic tree. Sholl and branch order analysis showed a decrease in the
      most distal and higher order branches. We suggest that afferent input plays a
      specific role in shaping the morphology of dendritic trees by regulating the
      formation or maintenance of high-order distal branches.

PMID- 12205706
TI  - Central projections of the utricular nerve in the gerbil.
AB  - The central projections of primary afferent fibers in the utricular nerve, which
      convey linear head acceleration signals to neurons in the brainstem and
      cerebellum, are not completely defined. The purpose of this investigation was
      twofold: 1) to define the central projections of the gerbil utricular afferents
      by injecting horseradish peroxidase (HRP) and biotinylated dextran amine (BDA)
      into the utricular macula; and 2) to investigate the projections of individual
      utricular afferents by injecting HRP intracellularly into functionally identified
      utricular neurons. We found that utricular afferents in the gerbil projected to
      all divisions of the vestibular nuclear complex, except the dorsal lateral
      vestibular nucleus. In addition, terminals were observed in the interstitial
      nucleus of the eighth nerve, nucleus Y, external cuneate nucleus, and lobules I,
      IV, V, IX, and X of the cerebellar vermis. No projections appeared in the
      flocculus or paraflocculus. Fibers traversed the medial and intermediate
      cerebellar nuclei, but terminals appeared only occasionally. Individual utricular
      afferents collateralize extensively, projecting to much of the brainstem area
      innervated by the whole of the utricular nerve. This study did not produce
      complete filling of individual afferent collateral projections into the
      cerebellar cortex.

PMID- 12205707
TI  - Dopamine depletion causes fragmented clustering of neurons in the sensorimotor
      striatum: evidence of lasting reorganization of corticostriatal input.
AB  - Firing during sensorimotor exam was used to categorize single neurons in the
      lateral striatum of awake, unrestrained rats. Five rats received unilateral
      injection of 6-hydroxydopamine (6-OHDA) into the medial forebrain bundle to
      deplete striatal dopamine (DA; >98% depletion, postmortem assay). Three months
      after treatment, rats exhibited exaggerated rotational behavior induced by L
      dihydroxyphenylalanine (L-DOPA) and contralateral sensory neglect. Electrode
      track "depth profiles" on the DA-depleted side showed fragmented clustering of
      neurons related to sensorimotor activity of single body parts (SBP neurons).
      Clusters were smaller than normal, and more SBP neurons were observed in
      isolation, outside of clusters. More body parts were represented per unit volume.
      No recovery in these measures was observed up to one year post lesion. Overall
      distributions of neurons related to different body parts were not altered. The
      fragmentation of SBP clusters after DA depletion indicates that a percentage of
      striatal SBP neurons switched responsiveness from one body part to one or more
      different body parts. Because the specific firing that characterizes striatal SBP
      neurons is mediated by corticostriatal inputs (Liles and Updyke [1985] Brain Res.
      339:245-255), the data indicate that DA depletion resulted in a reorganization of
      corticostriatal connections, perhaps via unmasking or sprouting of connections to
      adjacent clusters of striatal neurons. After reorganization, sensory activity in
      a localized body part activates striatal neurons that have switched to that body
      part. In turn, switched signals sent from basal ganglia to premotor and motor
      neurons, which likely retain their original connections, would create mismatches
      in these normally precise topographic connections. Switched signals could
      partially explain parkinsonian deficits in motor functions involving
      somatosensory guidance and their intractability to L-DOPA therapy-particularly if
      the switching involves sprouting.

PMID- 12205708
TI  - In vivo modulation of a cortical functional sensory representation shortly after
      topical cholinergic agent application.
AB  - The aim of the present study was to determine whether cholinergic increase in the
      size of a functional representation (collective evoked response from a large
      population of neurons) can be observed shortly (within an hour) after treatment
      onset and whether nicotinic receptors can participate in this type of modulation.
      Cholinergic agonist application has been found previously to increase the
      response of a single cortical neuron to a stimulus. Also, pairing cholinergic
      basal forebrain stimulation with delivery of a tone has been reported to increase
      the size of that tone's functional representation. Whereas the increase in a
      single cortical neuron response can occur within seconds after cholinergic
      agonist application, to date the increase in the size of a functional
      representation has only been investigated within one to several weeks after the
      onset of pairing basal forebrain stimulation with tone delivery. Furthermore,
      primarily muscarinic receptors have been implicated in these types of changes in
      cortical activity. By using optical imaging of intrinsic signals in vivo, we
      found that the size of a whisker's functional representation in the primary
      somatosensory cortex of the rat increases substantially within 69 or 46 minutes
      after topical application of either a muscarinic or nicotinic agonist to the
      exposed cortex, respectively, and decreases within 23 minutes after topical
      application of a muscarinic antagonist. For each cholinergic agent, we verified
      that delivery of a cholinergic agent by means of topical application can lead to
      the agent's successful penetration through the cortical layers in the time
      allotted to complete an imaging experiment. Furthermore, the time course of
      penetration for each agent was characterized. Based on the combined
      imaging/penetration results, we speculate on potential sites of cholinergic
      action in the cortex. Irrespective of the exact mechanism of action, we
      demonstrate here that an increase in the size of a functional sensory
      representation can occur shortly by means of activation of either nicotinic or
      muscarinic receptors.

PMID- 12205709
TI  - Expression of EphB receptors and EphrinB ligands in the developing chick auditory
      brainstem.
AB  - Nucleus magnocellularis (NM) in the avian auditory brainstem receives auditory
      input from nerve the VIIIth and projects bilaterally to nucleus laminaris (NL).
      This projection preserves binaural segregation in that ipsilateral NM projects to
      dorsal dendrites of NL and contralateral NM projects to ventral dendrites of NL.
      We have begun to examine the molecular signals that influence segregation of
      inputs onto discrete regions of NL cells. We previously showed that the Eph
      receptor, EphA4, is expressed selectively in the dorsal NL neuropil from
      embryonic day (E) 9 to E11, when NM axons grow into the NL neuropil. This
      asymmetric distribution suggests that EphA4 acts as a guidance molecule during
      binaural segregation. We report here on the developmental changes in the
      expression of two other Eph receptors, EphB2 and EphB5, and two ligands, ephrin
      B1 and ephrin-B2, in the chick auditory brainstem. These proteins are expressed
      in the auditory nuclei during the maturation of the NM-NL projection. EphB2,
      EphB5, and ephrin-B1 are expressed in dorsal and ventral NL neuropil and at the
      midline of the brainstem at E10-E12. At this age, ephrin-B2, a ligand for EphB
      receptors and for EphA4, is expressed in NL cell bodies and NM-NL axons. The
      expression of these proteins diminishs in the posthatch ages examined. These
      results suggest that several members of the Eph family are involved in maturation
      of the nuclei and their projections. Moreover, ephrin-B2 in growing axons may
      interact with the asymmetrically expressed EphA4 during the establishment of
      binaural segregation.

PMID- 12205710
TI  - Medial forebrain bundle axotomy during development induces apoptosis in dopamine
      neurons of the substantia nigra and activation of caspases in their degenerating
      axons.
AB  - There is growing evidence that programmed cell death may play a role in
      degenerative neurologic disease. The caspases are a family of cell death proteins
      that mediate proteolytic cascades in the death process. Although there is clear
      evidence that caspases play a role in the destruction of the components of the
      neuronal soma, it has been controversial whether they play a role in the
      degeneration of axons that accompanies the death of the cell body. It is
      important to define the molecular mechanisms of axonal degeneration, because
      terminal degeneration may occur early in neurodegenerative disease. We have
      therefore investigated whether caspases play a role in axonal degeneration in the
      dopaminergic nigrostriatal system following axotomy of the median forebrain
      bundle during development. We find that this lesion induces apoptosis in midbrain
      dopaminergic neurons at the level of the cell soma. Concomitantly with this
      induction of apoptosis, degeneration of dopaminergic axons occurs and is
      characterized by the formation of axonal swellings and spheroids.
      Immunohistochemical analysis reveals that the activated form of caspase-3 and a
      caspase cleavage product of beta-actin are abundantly expressed in these
      degenerating fibers. We conclude that caspases are activated in degenerating
      dopaminergic axons as the somata undergo programmed cell death in this model.
      These results raise the possibility that caspase activation may occur in other
      programmed cell death contexts for these neurons, and, if this is so, then their
      inhibition may be a useful therapeutic target.

PMID- 12205711
TI  - Developmental cell death in vivo: rescue of neurons independently of changes at
      target tissues.
AB  - Programmed cell death is a prominent feature of neural development that is
      regulated by a variety of cell-cell interactions. We used the avian ciliary
      ganglion to dissect the relative contributions of target tissues vs. ganglionic
      inputs in regulating cell death. The two populations of the ciliary ganglion
      innervate different targets: choroid neurons innervate vasculature, whereas
      ciliary neurons innervate the iris and ciliary body. By counting after labeling
      all neurons with Islet-1 and choroid neurons with anti-somatostatin, we
      determined that alpha-bungarotoxin (alpha-btx) at 12.5 microg/day rescued only
      ciliary neurons, whereas 75 microg/day rescued both ciliary and choroid neurons.
      It is unlikely that alpha-btx acted by blocking nerve transmission at both
      targets because the choroid vasculature lacked transcripts for alpha-btx binding
      molecules. In addition, no inherent trophic activity could be ascribed to alpha
      btx, and survival could not be attributed to differences in total trophic
      activity of eyes from saline vs. alpha-btx-treated embryos. In contrast, the
      alpha7 antagonist alpha-methyllycaconitine (MLA) rescued ciliary neurons at 2.6
      microg/day, whereas 26 microg/day rescued choroid neurons. Nerve terminals of
      ciliary neurons rescued with alpha-btx were significantly larger; however,
      differences in nerve terminal size or branching of axons were not observed in
      ciliary neurons rescued with MLA or choroid neurons rescued by either MLA or
      alpha-btx. Our results suggest that neuronal survival can be promoted
      independently of changes at the target tissues when orthograde signals acting by
      means of neuronal alpha7 nicotinic receptors are blocked.

PMID- 12205713
TI  - Symptoms of schizophrenia and neurocognitive test performance.
AB  - Schizophrenic in-patients were rated on factor-derived symptom dimensions based
      on negative and positive symptom ratings. Participants were administered
      neuropsychological tests (digit span, digit vigilance, logical memory, and Trails
      A and B) and then instructed on how to improve performance on the tests. Follow
      up tests were administered shortly after coaching. Comparisons of pre- and post
      instruction test scores indicated that the patient group was able to improve
      significantly their performance on the tests after coaching. Symptom dimensions
      were predictive of improved post-instruction test performance beyond the impact
      of the level of pre-instruction scores. Symptoms of disorganization and negative
      symptoms were related to lack of ability to improve performance on one or more of
      the tests, and positive symptoms and premorbid adjustment were associated with
      improved post-instruction performance. The symptom dimensions provide a
      potentially useful approach to reducing heterogeneity within samples of
      schizophrenic patients.

PMID- 12205712
TI  - Ebony protein in the Drosophila nervous system: optic neuropile expression in
      glial cells.
AB  - The Drosophila ebony mutation (Bridges and Morgan, [1923] Publs Carnegie Inst
      Wash 327:50) reveals a pleiotropic phenotype with cuticular and behavioral
      defects. To understand Ebony function in the nervous system, particularly in
      transmission of the visual signal, it is essential to know the cell type and
      temporal characteristics of its expression throughout development. Therefore, we
      raised an antiserum against an Ebony peptide to detect the protein in whole-mount
      and slice preparations of Drosophila. Attention was focused on ebony expression
      in the adult optic neuropiles of the fly. Colocalization of Ebony with neuronal
      or glial cell markers in frozen sections showed non-neuronal expression of ebony
      in the lamina and medulla neuropiles. Furthermore, colocalization with glial cell
      markers demonstrated glial expression of ebony in epithelial glia of the lamina
      and neuropile glia of the distal medulla. This finding was confirmed for the
      lamina epithelial glia by electron microscopic examination of immunolabeling by
      using the diaminobenzidine method. These glia have in common that they match the
      two sites of histamine release from the compound eye's photoreceptors. Possible
      ways in which the biochemical activity of Ebony might function with respect to
      histamine release are considered.

PMID- 12205714
TI  - Psychotherapists' representations of their patients.
AB  - Using a new measure, the Patient Representation Inventory (PRI), this study
      investigated the nature of psychotherapists' working clinical models of their
      patients. The data provided by 73 therapists suggest that, regardless of
      experience level or theoretical orientation (cognitive-behavioral or
      psychodynamic), therapists tend to evoke such representations by accessing the
      words spoken during sessions and by recreating visual images of their patients'
      nonverbal contributions to the therapeutic dialogue. These representations tend
      to be in the service of more deeply understanding patients; their affective tone
      is suggestive of empathy, authenticity, and involvement. More-experienced
      therapists tend to evoke representations that rely largely on bodily sensations
      and the emotional atmosphere reflective of clinical interactions. Apparently,
      similarities and differences among therapists can be studied not only at the
      manifest level of clinical work, but at the representational level as well.

PMID- 12205715
TI  - Diagnosing complicated grief: a closer look.
AB  - Over the past decade, a number of researchers have proposed a separate DSM
      category for complicated grief. Recently, there have been attempts to determine
      empirically the number and nature of variables comprising the complicated-grief
      syndrome. The present research addresses one such procedure for defining these
      variables. Combining a past methodology that demonstrated the relative utility of
      one classification of complicated grief (Worden, 1991) with dimensional concepts
      derived from other classifications, the present research concludes that a
      relatively small number of variables account for the concept. These findings are
      discussed not only in terms of previous research on Worden's categorization and
      more recent classifications, but, more importantly, in terms of the more global
      theoretical and methodological issues surrounding the definition(s) of
      complicated grief.

PMID- 12205716
TI  - Correspondence between supervisors and trainees in their perception of
      supervision events.
AB  - The focus of this study is on how the participants in 16 supervisory dyads
      perceive the content and process in a supervisory session, and on the meaning
      they attach to supervisory events. A central issue is to what degree the
      participants in each dyad correspond in their perceptions and evaluation of
      supervisory events. Another question is how lack of correspondence affects the
      trainees' experience of satisfaction with the supervision. A majority of the
      dyads were rated low or moderate in correspondence, and it is discussed whether
      the influence of low correspondence on trainee satisfaction may be related to
      supervisory intentions and style characteristics. A main point in the discussion
      is whether role ambiguity may be related to obscure communication and reduced
      correspondence, and it is suggested that more attention should be paid to
      negotiating and renegotiating rules for the supervisory relationship.

PMID- 12205717
TI  - Comparison of seven-subtest and Satz-Mogel short forms of the WAIS-III.
AB  - Intellectual functioning remains an important domain of functioning to be
      measured. To reduce the lengthy administration time, numerous short forms of the
      WAIS-III have been devised. The present study aimed to compare two methods of
      applying short forms of the WAIS-III within a clinical population. The results
      revealed that both item-reduced and selected subtest short forms provide
      excellent predictions of full administration WAIS-III summary and index scores.
      The Satz-Mogel short form appeared to provide higher predictive power than the
      seven-subtest short forms and accounted for a higher number of cases within 6
      points of the obtained scores from the full administration. However, the Satz
      Mogel short form was inferior to the seven-subtest short forms in terms of the
      reliability of the index and summary IQ scores. As found in previous research, a
      trade-off occurs between the predictive power and the reliability of a short
      form.

PMID- 12205718
TI  - Predictors of graduate student attitudes toward prescription privileges for
      psychologists.
AB  - The issue of gaining prescription privileges and its potential impact on the
      field of clinical psychology has special relevance for graduate students. This
      study was designed to investigate clinical graduate students' attitudes toward
      prescription authority, identify salient variables that contribute to these
      attitudes, and ascertain preferred models of training. Only 42.5% of respondents
      personally desired to obtain prescription privilege, although 61.8% of
      respondents favored efforts of the American Psychological Association to acquire
      prescription authority. Proponents and opponents were compared on their ratings
      of positive and negative aspects of the debate. There was strong agreement that
      the training should not be predoctoral and that it should lead to board
      certification. The strongest predictors of graduate students' attitudes were
      concerns about fundamental change to the field, malpractice premiums, and whether
      they considered it a logical extension of the field. This study provides a
      framework for understanding important factors influencing the decision-making
      process among clinical psychology graduate students.

PMID- 12205719
TI  - Childhood antecedents of adult sense of belonging.
AB  - Sense of belonging has been proposed to be a basic human need, and deficits in
      sense of belonging have been linked to problems in social and psychological
      functioning. Yet, there is little evidence about what early life experiences
      contribute to sense of belonging. The purpose of this study was to examine
      potential childhood antecedents of adult sense of belonging. The sample consisted
      of 362 community college students ranging in age from 18 to 72 years, with a mean
      age of 26 years. Measures included the Sense of Belonging Instrument, the
      Parental Bonding Instrument, and the Childhood Adversity and Adolescent Deviance
      Instrument. Multiple regression analysis was used to correlate childhood
      antecedents with adult sense of belonging. The final reduced model included 12
      variables, which accounted for 25% of the variance in sense of belonging.
      Significant positive antecedents with a relationship with sense of belonging were
      perceived caring by both mother and father while growing up, participation in
      high school athletic activity, and parental divorce. Significant negative
      variables with a relationship with sense of belonging included perceived
      overprotection of father, high school pregnancy, family financial problems while
      growing up, incest, and homosexuality. Knowledge of these factors should
      influence interventions with families regarding child-rearing and parenting
      practices, mediating the effects of crises during childhood such as divorce and
      teen pregnancy, and the interpersonal growth needs of teenagers.

PMID- 12205720
TI  - Personality and deviant sexual fantasies: an examination of the MMPIs of sex
      offenders.
AB  - A sample of 228 sex offenders and nonsex offender controls were divided into two
      groups, based on the presence or absence of deviant sexual fantasies, as
      determined by their replies to the Clarke Sex History Questionnaire Fantasy
      Scales. The sex offenders were divided into six groups based on sexual
      preferences and criminal history. There were 14 heterosexual pedophiles, 23
      homosexual pedophiles, 51 exhibitionists, 17 incest offenders, 24 sexual
      aggressives, and 57 multiple/miscellaneous offenders as well as 42 nonviolent
      nonsex offender controls. A 2 (fantasy group) x 7 (sex offender group)
      multivariate analysis with age and education as covariates was used to compare
      the MMPI validity scales (L, F, and K) and the 10 clinical scales as dependent
      variables. Deviant fantasizers had more clinically significantly scores on the F,
      Psychopathic Deviate, Masculinity-Femininity, Paranoia, and Schizophrenia Scales
      compared to nondeviant fantasizers, regardless of group membership. Results
      suggest that deviant fantasizers may be more socially alienated and less
      emotionally stable than nondeviant fantasizers, although few were diagnosed as
      psychotic. The sex offender and control groups showed considerable overlap on
      mean MMPI Scales. The groups tended to differ in level of depression and extent
      of persecutory ideas, but the multivariate sex offender group effect was not
      statistically significant when problems of inhomogeneity of variance were
      corrected. There was no interaction of fantasy groups and sex offender groups,
      indicating that the two factors can be considered independently.

PMID- 12205721
TI  - A longitudinal study of the effects of seizure symptoms on the Minnesota
      Multiphasic Personality Inventory-2 (MMPI-2) clinical interpretation.
AB  - This study investigated whether the Minnesota Multiphasic Personality Inventory-2
      (MMPI-2) items reflecting seizure symptoms spuriously inflate MMPI-2 scores in
      persons with epilepsy. In a repeated measures prospective design, patients with
      epilepsy completed the MMPI-2 prior to epilepsy surgery and again two years later
      when they were either seizure-free or not seizure-free. Compared to baseline
      scores, only seizure-free patients showed a decline in endorsement of seizure
      items, and only on one scale, Hypochondriasis (Hs). Clinical profiles were not
      meaningfully different when readministered when seizures were no longer present.
      Moreover, profiles generated by individuals with and without seizures were not
      significantly different. We conclude the MMPI-2 is a valid test in an epilepsy
      population, as seizure content did not alter its clinical interpretation. In
      using the MMPI-2 in patients with epilepsy, a modest correction on the Hs and
      Schizophrenia (Sc) scales is warranted in selected cases. In MMPI-2 research,
      assessing both statistical and clinical significance is recommended.

PMID- 12205722
TI  - An analysis of the influence of insurance sponsorship on MMPI changes among
      patients with chronic pain.
AB  - Pretreatment and posttreatment MMPI scores of 821 patients who completed a
      chronic pain program were submitted to a multivariate analysis of variance,
      examining the effects of age, gender, and insurance sponsorship. With the
      exception of scale 9, all clinical scales were significantly lower at
      posttreatment. Only the sponsorship variable was found to be a moderator variable
      for these treatment effects, with decreases on scales 1, 2, 3, and 0 attenuated
      in subjects with Worker's Compensation sponsorship compared to other sponsorship.
      Suggestions for further multivariate research with this population are discussed.

PMID- 12205723
TI  - Remission, recovery, relapse, and recurrence in eating disorders:
      conceptualization and illustration of a validation strategy.
AB  - In a consensus-building process a group of experts from 19 European countries
      (COST Action B6) adapted the terms partial and full remission, relapse, recovery,
      and recurrence according to principles described by Frank et al. for depression.
      The empirical validity of the operationalizations was illustrated by longitudinal
      data on the post treatment course of 233 anorectic and 422 bulimic patients
      (diagnosed according to DSM-IIIR) from the German Project TR-EAT. These data were
      collected 2.5 years after admission using the Longitudinal Interval Follow-up
      Evaluation (LIFE) and statistically explored by survival-analysis. It was
      demonstrated that these consensus definitions measure what they intend to
      measure. They open a longitudinal perspective in that one can learn not only
      whether, but also when and with what probability patients change for the better
      or worse. Data suggest that persistence of symptom improvement has different
      implications for anorexia and bulimia nervosa. For example, relapse prevention
      would be most beneficial for bulimic patients for about 4 months after key
      symptoms remit, while this would be of less importance for anorexic patients. It
      is discussed whether and how this longitudinal approach can contribute to an
      empirically based rationale for targeted and individualized treatment.

PMID- 12205724
TI  - The comparison of the behavioral observation system and the brief psychiatric
      rating scale-expanded.
AB  - The construct validity of the Behavioral Observation System (BOS), an
      observational instrument used by line staff to rate psychopathological behaviors,
      was studied using comparisons with the Brief Psychiatric Rating Scale-Expanded
      version (BPRS-E). A sample of 100 inpatient participants was rated using the BPRS
      E on the same day they were rated by line staff using the BOS. Pearson product
      moment correlations were performed, supporting good convergence and divergence.
      Principle component analysis on the six BPRS-E scales and the four BOS scales
      resulted in a three-factor finding. This analysis was supportive of construct
      validity. Uses of the BOS in light of these findings were discussed.

PMID- 12205725
TI  - Patterns of substance use in treatment-seeking problem gamblers: impact on
      treatment outcomes.
AB  - Accumulating evidence suggests that treatment-seeking problem gamblers have high
      rates of substance abuse. However, relatively little is known about the relation
      between gambling problems and specific psychoactive substances apart from alcohol
      and methadone-treated opiate addicts. In this study of 169 individuals seeking
      outpatient treatment for problem gambling, lifetime drug use and medication use
      were very high. Approximately half of the sample were using a psychiatric
      medication at the time they sought gambling treatment while very few individuals
      were using other drugs. Gambling treatment outcomes were unrelated to history of
      drug or medication use. No evidence was found for substitution of psychoactive
      substance use for gambling during the follow-up year. These findings indicate
      that gamblers are more likely to be involved with drug and medication use
      compared to the general population, but that such histories are not associated
      with gambling treatment outcomes.

PMID- 12205726
TI  - Countertransference management and therapy outcome: an initial evaluation.
AB  - The relationship between therapist countertransference management ability and
      therapy outcome was examined. Participants were 32 therapist-trainees and their
      clinical supervisors. Supervisors completed the Countertransference Factors
      Inventory (CFI) with regard to their supervisees. The CFI assesses five therapist
      characteristics thought to comprise countertransference management: Self-Insight,
      Self-Integration, Anxiety Management, Empathy, and Conceptualizing Skills. Both
      trainees and their supervisors rated the degree of improvement for each client
      seen in therapy. Results indicated that the CFI total score and the subscales of
      Anxiety Management and Conceptualizing Skills were positively related to both
      trainee and supervisor ratings of outcome; Self-Integration was related to
      trainee, but not supervisor, outcome ratings.

PMID- 12205727
TI  - Child-rearing practices and psychological disorders in children: cross-cultural
      comparison of Korea and Australia.
AB  - The present study was designed to explore cultural differences in the
      relationship between parenting behaviors and psychological adjustment of the
      child. Mother-son interaction behaviors of 37 Korean boys (11 with Anxiety
      Disorder, 10 with Externalizing Disorders and 16 Non-clinical boys) and 54
      Australian boys (20 with Anxiety Disorder, 17 with Externalizing Disorders and 17
      Non-clinical boys) between the ages of 7 and 15 were compared in terms of
      parental negativity and involvement. The results indicated that Korean mothers
      displayed more overall negativity and lower overall involvement than Australian
      mothers. Furthermore, anxiety diagnosis was associated with low maternal
      involvement in the Korean subjects, while in the Australian subjects, high
      maternal involvement was associated with clinical status in the child.

PMID- 12205728
TI  - Comparison of sevoflurane-nitrous oxide and target-controlled propofol with
      fentanyl anesthesia for hysteroscopy.
AB  - A randomized prospective study was performed on the anesthetic induction,
      maintenance, and recovery characteristics of sevoflurane-nitrous oxide, compared
      to that of target- controlled propofol and fentanyl anesthesia, for forty day
      case hysteroscopic surgery. The patients in the sevoflurane group (n = 20)
      received sevoflurane-nitrous oxide for both induction (8%) and maintenance (1 -
      2%) of anesthesia, while the patients in the propofol group (n = 20) received
      target-controlled propofol (4 micro g/ml, 3-6 micro g/ml as occasion demanded)
      with fentanyl (1 micro g/kg). In both groups, the airway was maintained by a
      facemask with the patient breathing spontaneously during the surgery. The mean
      times to unconsciousness and readiness for surgery were similar in both groups,
      with those for the sevoflurane group, compared to the propofol group being 80.4
      +/- 18.9 vs. 83.6 +/- 38.8 sec, and 220.1 +/- 76.9 vs. 231.0 +/- 95.4 sec,
      respectively. Propofol was associated with significantly higher incidences of
      involuntary movement (30% vs. 5%) and apnea (35% vs. 0%) during the induction
      period than with sevoflurane. Hemodynamic variables were similar with the
      exception of significantly lower blood pressures during the first 5 minutes of
      induction with propofol. Emergence times to eye opening, hand squeezing and
      orientation for sevoflurane compared to propofol were: 316.6 +/- 79.3 vs. 507.4
      +/- 218.8 sec, 390.0 +/- 69.3 vs. 653.1 +/- 201.6 sec and 380.6 +/- 80.8 vs.
      666.3 +/- 208.7 sec, respectively, all of these being significantly faster for
      sevoflurane than propofol. The postanesthetic Aldrete's recovery scores of the
      patients immediately after surgery were higher in the sevoflurane group. Propofol
      was associated with more drowsiness, with sevoflurane being associated with more
      nausea, in the recovery period; however, neither delayed the time to discharge
      (103.7 +/- 28.1 vs. 99.0 +/- 36.2 min). In conclusion, sevoflurane-nitrous oxide
      appears to be superior for day-case hysteroscopic surgery, than target-controlled
      propofol with fentanyl, with regards to the speed of recovery from anesthesia and
      the return to hemodynamic stability.

PMID- 12205729
TI  - Altered expression of Lewis antigen on tissue and erythrocytes in gastric cancer
      patients.
AB  - To elucidate the clinical significance of phenotypic alterations of Lewis antigen
      in gastric cancer patients, we investigated Lewis antigens by analyzing the
      genotypes of the Le and Se genes and by comparing the results obtained with the
      phenotypic expression of Lewis antigen in gastric cancer tissue and blood cells.
      One hundred and twenty gastric cancer patients were examined and compared with
      respect to Lewis blood phenotype and genotype. The expression of Le(a), Le(b),
      sialylated Le(a), and sialylated Le(x) antigens was immunohistochemically
      examined in uninvolved gastric mucosa, intestinal metaplasia, and cancerous
      tissue. We also analyzed the significance of Lewis antigen expression by
      analyzing patient survival. The frequencies of the Lewis phenotypes of RBCs
      corresponding to Le(a+b-), Le(a-b+), and Le(a-b-) were 16%, 58%, and 26%,
      respectively. The Le and le allele gene frequencies calculated from genotyping in
      gastric cancer patients were 0.623 and 0.377, respectively. The frequency for
      Le(a-b-) of the RBC phenotype had a tendency to be higher in cancer patients than
      in normal healthy Koreans. However, no difference in the Lewis gene frequency was
      found between these gastric cancer patients and healthy persons. The phenotype of
      Le(a-b+) was most prevalent in uninvolved gastric mucosal tissue, whereas the
      most prevalent form in tumor tissue was Le(a-b-). Sialyl-Le(a) and sialyl-Le(x)
      antigens were hardly detectable in uninvolved gastric mucosa, whereas the two
      antigens were expressed highly in intestinal metaplastic mucosa and tumor cells.
      In conclusion, the loss of Lewis antigen expression in tissue and on RBCs in
      gastric cancer patients is not a result of genetic influences, but rather a
      result of sialylation in tissue. We also confirm that poor prognosis is
      associated with dimeric sialyl-Le(x) and vascular spread.

PMID- 12205730
TI  - The effects of sulphasalazine on urinary excretion of the hydroxypyridinium
      crosslinks of collagen in patients with rheumatoid arthritis.
AB  - Secondary osteoporosis is a feature of rheumatoid arthritis (RA). In recent
      years, several attempts have been made to develop specific markers for monitoring
      connective tissue metabolism in arthritic diseases. Our purpose, in this study
      was to assess pyridinium crosslinks (PYD and DPYD) excretion in relation to the
      activity of RA (changes related to sulphasalazine treatment). Fourty
      premenopausal female patients with active RA (mean age; 36.0 +/- 7.2 years), 20
      postmenopausal women with active RA (mean age; 60.0 +/- 6.8 years), 23
      postmenopausal women with OA (mean age; 56.1 +/- 6.6 years) and 17 premenopausal
      healthy subjects (mean age; 28.3 +/- 4.28 years) were enrolled in our study. All
      of the 40 premenopausal female patients with active RA were given sulphasalazine.
      The mean follow up period for these patients was 10.3 +/- 1.1 months. In all of
      these patients, urine samples were collected both in the active and in the
      inactive periods. Urine PYD and DPYD levels were measured by ELISA. Urine PYD
      levels were significantly higher in the active period (14.01 +/- 3.16 nmol/mmol
      cr) than in the inactive (8.25 +/- 4.23 nmol/mmol cr) period in patients with
      premenopausal RA (p < 0.05). Urine PYD levels were significantly high in
      postmenopausal active RA patients (19.06 +/- 3.26 nmol/mmol cr) compared to
      premenopausal active and ind inactive, postmenopausal inactive RA patients,
      osteoarthritis and healthy controls. Urine DPYD excretion was similar in patients
      with premenopausal RA in the active (7.46 +/- 2.13 nmol/mmol cr) and inactive
      periods (5.08 +/- 0.87 nmol/mmol cr) (p > 0.05). In active premenopausal RA
      patients, a correlation was found between PYD excretion and RAI, ESR, CRP and
      functional capacity (r=0.5729 p < 0.01, r=0.5953 p < 0.01, r=0.6125 p < 0.01 and
      r=0.6232, p < 0.01 respectively). But in the inactive period, no such correlation
      was was evident. In disease activity parameters did not correlate with DPYD
      excretion in either the active or the inactive period. As a result, urine PYD
      excretion was significantly high in patients with active RA. During
      sulphasalazine treatment, urine PYD levels decreased. This is attributed to
      improvement in bone destruction.

PMID- 12205731
TI  - Reorganization of cortical language areas in patients with aphasia: a functional
      MRI study.
AB  - The purpose of this study is to delineate the pattern of reorganization of
      cortical language areas using functional magnetic resonance imaging (fMRI) after
      rehabilitation therapy in patients with aphasia. Six right-handed aphasic
      patients were investigated. Causes of aphasia were intracerebral hemorrhages of
      the left basal ganglia in 3 patients, cerebral infarction of the left MCA in 2,
      and surgical resection of the frontotemporal lobes to control intractable
      epilepsy in 1. An auditory sentence completion task was used to activate brain
      language areas during the fMRI. Three patients with left frontal lesions showed
      activation in the right inferior frontal lobes while performing language tasks,
      whereas the other 3, whose lesions located at subcortical areas, showed
      activation in the bilateral frontal and temporal lobes. Our results demonstrated
      the differences in interhemispheric reorganization of the language network
      depending on the location of the lesion in aphasic patients. While the patients
      with subcortical lesion showed tendency of bilateral frontal activation, those
      with cortical lesion showed activation of the right frontal lobe.

PMID- 12205732
TI  - Laser photocoagulation repair of recurrent macula-sparing retinal detachments.
AB  - Laser photocoagulation was performed around a detached retina in 4 patients who
      developed localized retinal detachment after successful scleral buckling. The
      range of retinal redetachment in all 4 patients was no larger than that of the
      initial retinal detachment and did not go over the vascular arcade. No evidence
      of vitreous traction or proliferative vitreoretinopathy was observed in these
      cases. Laser photocoagulation was performed in 3 lines of gray-white burn around
      the detached retina. Retinal attachment occurred between 4 and 14 days of laser
      treatment in all cases. No procedure related complications were seen. Laser
      photocoagulation may be an alternative procedure for the treatment of redetached
      retina with little and shallow detachment, before considering resurgery.

PMID- 12205733
TI  - Comparison of gastric cancer surgery with versus without nasogastric
      decompression.
AB  - There is a widespread belief that nasogastric decompression in gastric cancer
      surgery allows better surgical field and leads to the reduction of postoperative
      complications. The aim of this study was to evaluate whether gastric cancer
      surgery can be safely performed without nasogastric decompression. From March to
      June 2000, 119 patients with gastric adenocarcinoma were randomized into either a
      tubeless group (n=56) or an intubated group (n=63). Exclusion criteria included a
      history of upper gastrointestinal bleeding and pyloric obstruction. No remarkable
      difference was found in the incidence of complications in the tubeless and
      intubated groups (mean 10.9%, p=0.945). The incidence of nasogastric tube
      insertion in the tubeless group was similar to the incidence of nasogastric tube
      reinsertion in the intubated group (p=0.747). Time to pass flatus was not
      different in the two groups (p=0.054), nor was the length of hospital stay
      (p=0.148). These results suggest that gastric cancer surgery can be performed
      safely without nasogastric decompression.

PMID- 12205734
TI  - Esophageal involvement in Behcet's disease.
AB  - Esophageal involvement in Behcet's disease is very rare, and normally is observed
      as aphtosis and esophagitis, but serious complications such as erosions,
      perforations, and stenosis may occur. We carried out this prospective study to
      evaluate the prevalence of esophageal involvement in Behcet's disease and to
      establish if routine endoscopy and/or manometry are necessary. Twenty-three
      patients who fulfilled the diagnostic criteria of the international study group
      for Behcet's disease were enrolled. None were taking drugs or had disease that
      might produce esophageal abnormalities or alter any existing changes due to the
      Behcet's disease itself. Twenty- three patients underwent
      esophagogastroduodenoscopy by a single observer. Esophageal biopsies were
      performed in thirteen patients and esophageal manometry in twenty. At the
      beginning of the study, the disease activity was defined by the presence of more
      than one symptom related to Behcet's disease, and upon the classification of
      Behcet's disease. Of the twenty three patients enrolled two were excluded from
      final analysis because of the presence of hiatus hernia. Thus, 13 men and 8
      women, ranging in age from 20 to 63 years with a mean age of 36.2 years were
      included. Ten patients (47.6%) had active disease and four (19%) complained of
      upper gastrointestinal symptoms at the time of the study. Fourteen patients had
      endoscopic, manometric and/or microscopic abnormalities. Esophageal manometry was
      performed in twenty patients and was abnormal in 7 cases (35%). Esophageal
      biopsies were done in 13 patients and revealed histopathological abnormalities in
      5 cases. Microscopic findings showed vasculities in one case, and non-specific
      inflammatory infiltration mainly consisting of neutrophils in 4 cases. Our
      results suggest that the prevalence of esophageal involvement in Behcet's disease
      is rather high and occur even in asymptomatic patients, but that this usually
      does not result in specific abnormalities.

PMID- 12205736
TI  - The roles of stromelysin-1 and the gelatinase B gene polymorphism in stable
      angina.
AB  - Matrix metalloproteinases contribute to vascular remodeling by breaking down
      extracellular-matrix while new matrix is synthesized. Of the variety of MMPs,
      stromelysin-1 and gelatinase B may have key roles in coronary artery
      atherosclerosis. Moreover, The 5A/6A polymorphism in the promoter region of the
      stromelysin-1 gene may be a pathogenetic risk factor for acute myocardial
      infarction. Gelatinase B (92-kDa type IV collagenase and MMP-9) is one of the
      MMPs found to be highly expressed in the disruption-prone regions of
      atherosclerotic plaques. C- to T substitution at the promoter site (-1562)
      resulted in the higher promoter activity of the T-allelic promoter. The R279Q
      polymorphism in exon 6 led to the substitution of adenosine by guanine, and was a
      common polymorphism in the general population. We evaluated the relation between
      these polymorphisms and stable angina, the severity of atherosclerosis in
      coronary artery disease, and in-stent restenosis after percutaneous coronary
      angioplasty. The study population was composed of 131 patients with stable angina
      (mean age 61.3 years, 89 males) and 117 control subjects (mean age 59.3 years, 59
      males). Coronary angiographies were performed in all cases at Yonsei University
      Cardiovascular Hospital from February 1998 to June 2000. The genotype for each
      polymorphism was determined using a SNaPshotTM kit and by restriction fragment
      length polymorphism (RFLP). The prevalence of 5A containing a polymorphism of the
      stromelysin-1 gene was higher in the stable angina group than in control
      patients, but no difference in the two polymorphisms of the gelatinase B gene was
      found between the two groups. By multiple logistic analysis, the 5A-allele of the
      stromelysin-1 gene was found to be an independent risk factor of stable angina
      with an odds ratio of 2.29 (95% CI; 1.19-4.38). However, the severity of
      atherosclerosis in coronary artery or in stent restenosis was not related to any
      polymorphism of stromelysin-1 or gelatinase B. Our results show that functional
      genetic variation of stromelysin-1 could be a significant risk factor for stable
      angina, and might play an important role in coronary atherosclerosis involving
      vascular remodeling.

PMID- 12205735
TI  - Renin-angiotensin-aldosterone system (RAAS) gene polymorphism as a risk factor of
      coronary in-stent restenosis.
AB  - Intimal proliferation is a main cause of in-stent restenosis. Over-excretion of
      angiotensin I converting enzyme (ACE) and aldosterone is reported to stimulate
      intimal hyperplasia and the genetic effect of these molecules may alter the
      process of in-stent restenosis. We hypothesized that the genetic polymorphisms
      that alter the expression of genes such as ACE I/D, CYP11B2-344C/T, and AGT M235T
      can affect in-stent restenosis. We analyzed the angiographic and clinical data of
      238 patients (272 stents) who underwent coronary stenting and follow-up
      angiography, and analyzed the genotypes of ACE I/D, CYP11B2-344T/C, and AGT
      M235T. There was no significant difference in age, sex, or lipid profiles between
      the patent and restenosis groups. Diabetes mellitus was more frequent in the
      binary restenosis group. Quantitative computer-assisted angiographic (QCA)
      analysis revealed that the risk of in-stent restenosis increased with lesion
      length and was inversely proportional to post- stenting minimal luminal diameter
      (MLD) and reference diameter. There was no difference in the frequency of binary
      restenosis between genotypes in each of the three genes. However, follow-up MLD
      was significantly smaller in the ACE DD genotype than in the ACE II or ID
      genotypes. Defining restenosis as MLD < 2 mm, the restenosis rate was
      significantly higher in the ACE DD genotype than in the ACE II or ID genotypes.
      There was no significant synergistic effect between the three gene polymorphisms.
      In conclusion, while the ACE I/D polymorphism promoted the progress of in-stent
      restenosis and was of clinical significance, the other potential variables
      examined did not correlate with in-stent restenosis.

PMID- 12205737
TI  - Influence of GnRH agonist and neural antagonists on stress-blockade of LH and
      prolactin surges induced by 17beta-estradiol in ovariectomized rats.
AB  - In our previous study, we demonstrated that immobilization stress blocked
      estrogen-induced luteinizing hormone (LH) surge possibly by inhibiting the
      synthesis and release of gonadotropin-releasing hormone (GnRH) at the
      hypothalamic level and by blocking estrogen-induced prolactin (PRL) surge by
      increasing the synthesis of dopamine receptor at the pituitary level in
      ovariectomized rats. The present study was performed to determine whether
      immobilization stress affects pituitary LH responsiveness to GnRH, and whether
      endogenous opioid peptide (EOP) and dopamine systems are involved in blocking LH
      and PRL surges during immobilization stress. Immobilization stress was found to
      inhibit basal LH release and to completely abolish LH surge. However, the
      intravenous application of GnRH agonist completely restored immobilization
      blocked LH surge and basal LH release. Treatment with naloxone did not exert any
      effect on immobilization-blocked LH surge but increased basal LH release during
      immobilization stress. Pimozide did not affect immobilization-blocked LH surge or
      basal LH release. Naloxone also decreased immobilization-induced basal PRL
      release, but had no effect on immobilization-blocked PRL surge. Immobilization
      increased basal PRL levels were augmented by pimozide treatment and
      immobilization-blocked PRL surge was dramatically restored by pimozide. We
      conclude that immobilization stress does not impair pituitary LH response to
      GnRH, and that the immobilization stress-induced blockage of LH surge is probably
      not mediated by either the opioidergic or the dopaminergic system. However,
      immobilization-blockade of PRL surge may be partly mediated by the dopaminergic
      system.

PMID- 12205738
TI  - The metabolism and liver toxicity of N,N-dimethylformamide in the isolated
      perfused rat liver.
AB  - N,N-dimethylformamide (DMF) is metabolized by the microsomal cytochrome p-450
      into mainly N-hydroxymethyl- N-methylformamide (HMMF), which further breaks down
      to N-methyformamide (NMF). However, the detailed mechanism of its toxicity
      remains unclear. We investigated the metabolism and the toxicity of DMF using the
      isolated perfused liver model. DMF was added to the recirculating perfusate of
      the isolated perfused rat liver at concentrations of 0, 10 and 25 mM. Samples
      were collected from the inferior vena cava at 0, 30, 45, 60, 75, and 90 minutes
      following addition of the DMF. The metabolites of DMF were analyzed using Gas
      chromatography (GC). The changes in the rate of oxygen consumption by the DMF
      were monitored during perfusion. The enzyme activities (aspartic
      aminotransferase:AST, alanine aminotransferase:ALT, and lactic
      dehydrogenase:LDH)) in the perfusate were monitored to see if DMF caused
      hepatotoxicity. As the perfusion progressed, the DMF concentration in the
      perfusate decreased, but the level of NMF increased to a maximum of 1.16 mM. The
      rate of oxygen consumption increased at DMF concentrations of 10 mM and 25 mM.
      However, when a known inhibitor of cytochrome p-450, SKF 525A (300 micro M), was
      used to pretreat the perfusate prior to the addition of the DMF, the rate of
      oxygen consumption was significantly inhibited, indicating the cytochrome p-450
      system was responsible for the conversion of DMF to NMF. On addition of the DMF,
      the activities of the enzymes AST, ALT and LDH were significantly increased a
      time and dose dependent manner. However, following pretreatment with SKF 525A,
      their releases were inhibited.

PMID- 12205739
TI  - The effect of alphaMSH analogues on rat bones.
AB  - Melanocortin is the downstream mediator of leptin signaling and absence of leptin
      signaling in ob/ob and db/db mice revealed the enhancement of bone formation
      through the central regulation. While alpha-melanocyte-stimulating hormone
      (alphaMSH) inhibits the secretion of interleukin-1alpha and tumor necrosis factor
      alpha from the inflammatory cells, alphaMSH can also enhance clonal expansion of
      pro B cells linked to stimulation of osteoclastogenesis. Therefore, we tested the
      effect of melanocortin on bones. alphaMSH analogues [(6)His]alphaMSH-ND and
      [(6)Asn]alphaMSH-ND were synthesized and the radio-ligand receptor binding- and
      cyclic AMP generating activity were analyzed in China Hamster Ovary cell line
      over- expressing melanocortin receptors. The EC(50) of [(6)His]alphaMSH-ND
      measured from melanocortin-1, 3, 4 and 5 receptors were 0.008 +/- 0.0045, 1.523
      +/- 0.707, 0.780 +/- 0.405, and 250.320 +/- 42.234 nM, respectively, and the
      EC(50) of [(6)Asn]alphaMSH-ND were 16.8 +/- 6.94, 271.8 +/- 21.95, 8.0 +/- 1.21,
      and 1132.5 +/- 635.46 nM, respectively. Four weeks after the subcutaneous
      injection of the analogues, the body weights in the [(6)His]alphaMSH-ND and the
      [(6)Asn]alphaMSH-ND treated groups (346.0 +/- 20.63 g vs. 350.0 +/- 13.57 g) were
      lower than that of the vehicle treated group (375.8 +/- 17.31 g, p < 0.05). There
      was no difference in the total femoral BMD measured by dual x-ray absorptiometry
      among the three groups. Among the three groups, there were no differences in the
      total numbers of crystal violet positive- or alkaline phosphatase positive
      colonies, in the expression of Receptor Activator of Nuclear Factor Kappa-B
      ligand on the tibia and the total number of multinucleated osteoclast-like cells
      differentiated from primary cultured bone marrow cells. From the above results,
      no evidence of bone gain or loss was found after treatment of the alphaMSH
      analogues peripherally.

PMID- 12205740
TI  - Effect of induced and spontaneous hypothermia on survival time of uncontrolled
      hemorrhagic shock rat model.
AB  - We examined the hypothesis that mild hypothermia (rectal temperature 34 degrees
      C) results in the same survival time, whether induced spontaneously or
      intentionally, during untreated, lethal, uncontrolled hemorrhagic shock in rats.
      Sixty-four Sprague-Dawley male rats were randomly assigned to normothermia (Nth)
      (n=19), spontaneous mild hypothermia (Sp.Hth) (n=25) or controlled mild
      hypothermia (Con.Hth) (n=20) groups. After blood withdrawal of 3 mL/100 g over 15
      minutes, followed by 75% tail amputation under spontaneous breathing and light
      anesthesia by i.p. injection of pentobarbital sodium, rats were observed without
      fluid resuscitation or hemostasis for 180 minutes or until death. The initial
      temperature of the Nth group was artificially maintained throughout the
      experiment. For the mild hypothermia groups, the Sp.Hth group was exposed to
      ambient temperature while the Con. Hth group was actively cooled to a target
      rectal temperature of 34 degrees C. In the Con.Hth group, all rats except one
      died before 180 minutes. All rats in the Nth group died within 38 minutes, and
      within 67 minutes in the Sp.Hth group. The average survival time was shortest in
      the Nth group at 20.3 +/- 5.3 minutes, followed by the Sp.Hth group at 30.1 +/-
      13.5 minutes, and the Con.Hth group at 81.9 +/- 39.8 minutes (p < 0.01). Tail
      bleed out volume was 0.51 +/- 0.19, 0.26 +/- 0.15 and 0.19 +/- 0.12 mL/100 g in
      the Nth, Sp.Hth and Con.Hth groups, respectively (p < 0.05). In conclusion,
      spontaneous mild hypothermia did not prolong the survival time as much as
      controlled mild hypothermia in the rat model for untreated, lethal, uncontrolled
      hemorrhagic shock.

PMID- 12205741
TI  - Evaluation of the cytotoxicity of polyetherurethane (PU) film containing zinc
      diethyldithiocarbamate (ZDEC) on various cell lines.
AB  - A polyetherurethane (PU) film containing 0.1% zinc diethyldithiocarbamate (ZDEC)
      is the international standard reference material for testing the in vitro
      cytotoxicity of polymer based biomaterials. Nowadays, culturing L929 or BALB/3T3
      cells in direct contact or in an extract dilution condition is the most
      frequently using method for evaluating the cytotoxicity from biomaterials and
      medical devices. However, the results often vary, because it is directly related
      to the cellular functions and the mechanism of the toxicity of the contacting
      cells. In this study, 13 cell lines originating from various tissues were used to
      detect the cytotoxic activities of a PU film containing 0.1% ZDEC (PU-ZDEC). The
      correlation between the reactivity zone size and the relative cytotoxicity by
      quantifying the released total protein from each cell in the direct contact
      testing method was investigated. Hepa-1c1c7 cells demonstrated the highest
      sensitivity in the reactivity zone size, while CHO/dhFr(-) cells were the most
      sensitive in terms of the relative cytotoxicity. A correlation between the two
      processes in each cell line was not found (r=-0.478). In the extract dilution
      method, which involved cultivating the cells in the medium with various ZDEC
      concentrations prepared by diluting the PU incubation, the cytotoxicity increased
      with increasing ZDEC concentration in all cell lines. The BALB/ 3T3 cells
      demonstrated the highest sensitivity in the extract dilution method. No
      correlation in a comparison of the relative cytotoxicity from the direct contact
      method with the extract dilution method in each cell line, was found (r=-0.445).
      In this experiment, Hepa-1c1c7, BALB/3T3, CHO/dhFr(-) and L-929 cells among the
      13 types of cell lines were the sensitive cell lines according to the two
      methods. The preliminary results suggest that a comparison of at least one or
      more cytotoxicity testing methods and many cell lines is necessary for an in
      vitro cytotoxicity test of biomaterials.

PMID- 12205742
TI  - A case of intravenous immunoglobulin-resistant Kawasaki disease treated with
      methotrexate.
AB  - Kawasaki disease, an acute febrile vasculitis of unknown etiology, is usually
      treated with high doses of immunoglobulin (IVIG) and aspirin. However, 20% of
      children show persistent or recurrent fever despite IVIG, and coronary artery
      aneurysm progression. In such cases of resistance to IVIG treatment, repeated
      IVIG administration or the initiation of steroid therapy, and the use of
      cyclophosphamide have been reported. We aimed to show in this study that
      methotrexate (MTX) may be used as a treatment for Kawasaki disease resistant to
      IVIG treatment. We report the case of a 6-year old boy who was admitted at
      another hospital with an initial complaint of a fever for 5 days and skin rashes
      for 3 days. The patients fever persisted despite three courses of IVIG (2 gm/kg,
      1 gm/kg, 1 gm/kg, respectively) over a 14-day period. On day 14 of his illness he
      showed a dilated right coronary artery, and on day 19 dexamethasone, at a daily
      dose of 0.3 mg/kg, was given but this resulted in defervescence. However, upon
      stopping the dexamethasone treatment, his fever recurred and he was transferred
      to our hospital. On days 31 and 38 of his illness, IVIG (400 mg/kg for 5 days,
      twice) was administered and from day 38 onwards the patient was given
      dexamethasone (0.6 mg/kg, daily) and MTX (10 mg/BSA, once weekly) whereupon his
      fever subsided and did not recur. On day 48 dexamethasone was replaced with
      prednisolone, which was subsequently tapered. The patient is now taking MTX and
      being observed on an outpatient basis. We report the case of a boy with IV
      globulin resistant Kawasaki disease, who after repeated infusions of IVIG and
      steroid therapy showed fever recurrence, which that subsided after MTX treatment.

PMID- 12205743
TI  - Bilateral putaminal hemorrhage with cerebral edema in hyperglycemic hyperosmolar
      syndrome.
AB  - Bilateral putaminal hemorrhages rarely occur simultaneously in hypertensive
      patients. The association of intracerebral hemorrhage with cerebral edema (CE)
      has been rarely reported in diabetic patients. We present a patient with
      bilateral putaminal hemorrhage (BPH) and CE during the course of hyperglycemic
      hyperosmolar syndrome (HHS). A 40-year-old man with a history of diabetes
      mellitus and chronic alcoholism was admitted with acute impaired mentality. His
      blood pressure was within the normal range on admission. Laboratory results
      revealed hyperglycemia and severe metabolic acidosis without ketonuria. After
      aggressive treatment, plasma sugar fell to 217 mg/dl, but brain CT showed BPH and
      diffuse CE. Our case demonstrated that HHS should be considered as a cause of BPH
      with CE. Initial brain imaging study may be recommended for patients with
      diabetic coma.

PMID- 12205744
TI  - Lymphadenoma arising in the parotid gland: a case report.
AB  - We report a case of lymphadenoma arising in the parotid gland. A 53-year-old
      female patient presented with a mass in the parotid gland. Grossly, it was a well
      demarcated solid mass measuring 3 cm in diameter. Microscopic examination
      revealed many cysts or duct-like structures in the background of the prominent
      lymphoid stroma, confirming a diagnosis of lymphadenoma. This particular case was
      thought to have arisen from an intraparotid lymph node. Lymphadenoma is a rare
      benign neoplasm of the salivary gland with partial resemblance to other salivary
      gland tumors, such as Warthin's tumor, cystadenoma, sebaceous lymphadenoma or
      mucoepidermoid carcinoma. Therefore proper recognition of this rare entity is
      warranted to avoid confusion in the diagnosis.

PMID- 12205745
TI  - Tuberculous subdeltoid bursitis with rice bodies.
AB  - A 41-year-old woman with a 2-month history of diffused swelling and persistent
      dull pain in her right shoulder was examined. Magnetic resonance imaging (MRI)
      findings revealed subdeltoid bursitis and rice bodies with normal surrounding
      tissue and shoulder joint. Arthoscopic debridement and biopsy of the subdeltoid
      bursa were performed. Histologic examination of the bursal tissue showed
      granulomatous tissue with typical caseous necrosis. A positive culture of
      Mycobacterium tuberculosis confirmed the diagnosis of tuberculosis. We report on
      the clinical, radiological and athological findings in a patient with tuberculous
      subdeltoid bursitis accompanied by multiple rice body formation without
      coexisting active bone and joint tuberculosis, and conduct a literature review.

PMID- 12205746
TI  - Massive hemoptysis after generalized tonic clonic seizure requiring mechanical
      ventilation.
AB  - A 38-year-old woman presented with massive hemoptysis (>200 mL/ 24 hours)
      occurring abruptly after generalized tonic clonic seizure. She experienced
      similar episodes of hemoptysis on three later occasions. Although the coexistence
      of hemoptysis and seizure has been reported, albeit rarely, as a clinical
      manifestation of postictal neurogenic pulmonary edema, massive hemoptysis after
      seizure is an extremely rare event with no recurrent cases of such episodes
      having ever been reported. The coexistence of hemoptysis and seizure increases
      the difficulty in diagnosis for the clinician. We describe the differential
      diagnosis among the diseases capable of causing seizure and hemoptysis.

PMID- 12205747
TI  - Endobronchial metastasis of uterine cervix cancer: a two case reports and a
      review of the literature.
AB  - Endobronchial metastasis from uterine cervix cancer defines a bronchoscopically
      visible nonpulmonary neoplasm metastatic to the bronchus and histologically
      identical to cervix cancer. Endobronchial metastasis of uterine cervix cancer is
      rare, therefore, it is difficult to diagnose without pulmonary symptoms or
      abnormal radiological findings. Moreover, endobronchial metastasis of a
      nonpulmonary neoplasm is difficult to differentiate from a primary pulmonary
      neoplasm. The incidence of endobronchial metastasis is increasing because of the
      regular use of fiberoptic bronchoscopy and the longer survival of cancer
      patients. This study describes our experience of two patients with pulmonary
      symptoms and abnormal radiologic findings during the follow up of uterine cervix
      cancer, who were diagnosed as having endobronchial metastasis from uterine cervix
      cancer, and includes a brief review of related articles.

PMID- 12205748
TI  - Vulvar myiasis.
AB  - BACKGROUND: To report a rare case of vulvar myiasis caused by Wohlfartia
      magnifica, including clinical and microscopic observations. CASE: A vulvar lesion
      was found in a 31-year old married female villager with the history of dropping
      fly larvae from vulva, vulvar pain and itching sensation. The larvae were
      identified as the species of Wohlfartia magnifica. The lesion was washed with
      batticon over a period of five days and the patient was discharged. CONCLUSION:
      Vulvar myiasis should be considered in the differential diagnosis of genital
      lesions. The diagnosis can be easily established based on microscopic features of
      the maggots, especially those relating to stigma structures.

PMID- 12205749
TI  - Reference to the mutations in the embB locus among Korean clinical isolates of
      Mycobacterium tuberculosis resistant to ethambutol.

PMID- 12205750
TI  - The living arrangements of new unmarried mothers.
AB  - We use data from the Fragile Families and Child Wellbeing Study to describe the
      living arrangements of new, unwed mothers and to examine the selection process
      that underlies choices of living arrangements. Our analysis goes beyond previous
      studies by examining a wide diversity of living arrangements for a homogenous
      sample of recent unwed mothers and by using information on both parents'
      demographic and human capital characteristics and the quality of their
      relationships. We find that about half the new unwed mothers are cohabiting at
      the time their children are born, and only 17% are living alone. We also find
      that mothers' choices of living arrangements are significantly related to
      parents' human capital, the quality of their relationship, and the cost of
      housing.

PMID- 12205751
TI  - An empirical analysis of the matching patterns of same-sex and opposite-sex
      couples.
AB  - We used 1990 Census data to compare the matching behaviors of four types of
      cohabiting couples: same-sex male couples, same-sex female couples, opposite-sex
      unmarried couples, and married couples. In general, we found evidence of positive
      assortative mating for all traits and across all types of couples. The positive
      assortative mating, however, is stronger for non-labor-market traits (e.g., age,
      education) than for labor-market traits (e.g., hourly earnings). Further, members
      of married couples are more alike with respect to most characteristics than are
      members of opposite-sex cohabiting couples, and members of opposite-sex
      cohabiting couples are more alike than are members of same-sex couples.

PMID- 12205752
TI  - How well can we track cohabitation using the SIPP? A consideration of direct and
      inferred measures.
AB  - Cohabitation is an alternative to marriage and to living independently for an
      increasing number of Americans. Still, research that explores links between
      living arrangements and economic behavior is limited by a lack of data that
      explicitly identify cohabiting couples. To aid researchers in using the Survey of
      Income and Program Participation's (SIPP) rich data to explore cohabitation
      issues, we consider direct and inferred measures of cohabitation. We find, first,
      that the use of inferred definitions (relative to direct measures) in the SIPP is
      likely to yield higher cohabitation rates in the United States by incorrectly
      coding roommates as cohabitors. Second, the SIPP (whether by direct or inferred
      measures) counts a significantly larger number of cohabiting couples than the
      widely used Current Population Survey (CPS). Third, spells of cohabitation occur
      less frequently and last longer when a direct measure of cohabitation is used
      than when either of the two inferred measures of cohabitation is used; ours is
      the first article to reveal this result.

PMID- 12205753
TI  - Only English by the third generation? Loss and preservation of the mother tongue
      among the grandchildren of contemporary immigrants.
AB  - We investigate whether a three-generation model of linguistic assimilation, known
      from previous waves of immigration, can be applied to the descendants of
      contemporary immigrant groups. Using the 5% Integrated Public Use Microdata
      Sample 1990 file, we examine the home languages of second- and third-generation
      children and compare the degree of their language shift against that among the
      descendants of European immigrants, as evidenced in the 1940 and 1970 censuses.
      Overall, the rates of speaking only English for a number of contemporary groups
      suggest that Anglicization is occurring at roughly the same pace for Asians as it
      did for Europeans, but is slower among the descendants of Spanish speakers.
      Multivariate models for three critical groups--Chinese, Cubans, and Mexicans-
      indicate that the home languages of third-generation children are most affected
      by factors, such as intermarriage, that determine the languages spoken by adults
      and by the communal context.

PMID- 12205754
TI  - Insights from longitudinal data on the earnings growth of U.S. foreign-born men.
AB  - Does the growth in earnings of foreign-born men exceed that of U.S. natives? We
      use longitudinal data on earnings from a Social Security Administration (SSA)
      database matched to the 1994 March Current Population Survey to shed new light on
      this important issue. We also examine the trend over time in the foreign-born
      men's earnings growth and illuminate the various ways that SSA data can be used
      to explore the earnings patterns of immigrants.

PMID- 12205755
TI  - Are black workers missing the connection? The effect of spatial distance and
      employee referrals on interfirm racial segregation.
AB  - I use data on the hiring practices and spatial location of firms in four cities
      to model the process of interfirm racial segregation. When I control for the
      spatial location of the firm, the use of employee referrals reduced the
      probability of hiring a black worker by 75% in firms that are less than 10%
      black. Among all firms, the results suggest that employee referrals are just as
      important as the geographic location of the firm in generating employment
      segregation: both increase the predicted level of interfirm racial segregation
      among blue-collar workers in the cities studied by about 10%.

PMID- 12205756
TI  - Mortality rates of elderly Asian American populations based on Medicare and
      Social Security data.
AB  - We present sex- and age-specific death probabilities for the elderly of six Asian
      American subgroups--Chinese, Filipino, Indian, Japanese, Korean, and Vietnamese-
      based on data from social Security Administration files. We determined ethnicity
      by combining race, place of birth, surname, and given name. The data source and
      ethnic determination are the same for deaths and the population at risk, avoiding
      the problem of noncomparability present when data for the numerator come from
      vital records and data for the denominator come from census records. We found
      that death rates for elderly Asian Americans are lower than those for whites, and
      that socioeconomic differences between subgroups do not translate into like
      differences in mortality.

PMID- 12205757
TI  - Self-reported work-limitation data: what they can and cannot tell us.
AB  - Despite their widespread use in the literature, the Current Population Survey
      (CPS) and similar surveys have come under attack of late. We put the criticisms
      in perspective by systematically examining what the CPS data can and cannot be
      used for in disability research compared to the National Health Interview Survey.
      On the basis of our findings, we argue (1) that the CPS can be used to monitor
      trends in outcomes of those with disabilities and (2) that the dramatic decline
      in the employment of people with disabilities we describe in the CPS during the
      1990s is not an artifact of the data.

PMID- 12205758
TI  - Has the Chinese family planning policy been successful in changing fertility
      preferences?
AB  - Has China's strict one-child policy been successful in changing fertility
      preferences? Using linked data from surveys conducted in four counties of
      northern China in 1991 and 1994, we compare reproductive behavior against prior
      fertility preferences and show when and where women change from wanting to not
      wanting more children. The acceptance of policy-sanctioned family size follows a
      development gradient and reflects the degree of enforcement. High acceptance
      occurs in the most urban, industrialized county and in the county with the most
      rigid family planning policy. Acceptance is weaker among women living in the
      poorest county and in the county where enforcement is most lenient.

PMID- 12205759
TI  - Reporting of fertility events by men and women in rural Gambia.
AB  - We conducted a survey of male and female fertility in rural villages in The
      Gambia and compared men and women's reports of recent pregnancy events in the
      aggregate and of children ever born for matched couples. Despite widespread
      polygyny and sex differences in fertility, men's and women's reports were
      similar. Small sex differences in reports of recent stillbirths and neonatal
      deaths were found. For matched couples, husbands reported 0.23 more children ever
      born than their wives on average, but discordant reporting had little effect on
      recent marital fertility rates. Modeling of discordant reports indicates that
      fertility reports are more likely to be underestimated by both men and women for
      their earliest marriages. Reliable fertility data can be collected from men in
      this population.

PMID- 12205760
TI  - It's your choice.

PMID- 12205761
TI  - On with the plan. Interview by Christian Duffin.

PMID- 12205762
TI  - Global killer.

PMID- 12205763
TI  - Barriers to healthy eating in the nursing profession: Part 2.
AB  - AIM: This is the second of two articles that report on work commissioned by the
      NHS Executive North West, to explore the perceived barriers to healthy eating
      within the nursing profession. METHOD: Observations were made of catering
      facilities within eight healthcare sites (six acute hospitals, an NHS walk-in
      centre and an NHS Direct site) across the North West region. Twenty four
      unstructured interviews were conducted with nurses and three were sampled from
      each healthcare site. RESULTS: Four main themes emerged as barriers to healthy
      eating: availability; variety; distance from catering facilities; and
      breaks/staffing levels/workload issues CONCLUSION: Respondents in this study do
      not consider their working environments to be conducive to healthy eating
      practices.

PMID- 12205764
TI  - Responding to people with a learning disability who offend.
AB  - AIM: This article reports on a small survey conducted in one NHS trust to
      establish the number of people with a learning disability known by staff to have
      committed, or be alleged to have committed, an offence. METHOD: A sample of 35
      members of staff who were likely to be in contact with this client group were
      sent questionnaires. Thirty responses were received, giving a response rate of 86
      per cent. RESULTS: A total of four nurses and two clinical psychologists were in
      contact with 31 individuals known or alleged to have committed an offence. These
      offences were mainly sexual and some were violent. Several individuals had
      committed a number of separate offences. Respondents felt that the needs of these
      individuals were not adequately met by current service provision. CONCLUSION: A
      planned inter-agency response is required to deal with people with learning
      disabilities who carry out criminal offences, rather than the current system
      which is vague in terms of allocating responsibility for action. The nurse's role
      in providing sexual health education for those with learning disabilities also
      needs to be considered in the light of the survey results.

PMID- 12205765
TI  - Evaluating nurse-led inpatient units.
AB  - This article highlights findings from three studies into nurse-led inpatient
      units. The results are not the same in each case, particularly with regard to
      length of stay, and the authors discuss the possible reasons for this. Further
      work is needed to develop NLIUs and identify cost savings.

PMID- 12205766
TI  - Myocardial infarction: Part 2.
AB  - Complications can and often do arise following myocardial infarction. Patients
      can be offered several tests and treatments. Nurses have an important health
      promotion role at all stages.

PMID- 12205767
TI  - Defining moment.

PMID- 12205768
TI  - Stem the flow.

PMID- 12205769
TI  - Anything's possible.

PMID- 12205770
TI  - Rites of passage.

PMID- 12205771
TI  - Family ties.

PMID- 12205772
TI  - Service evaluation of an autism diagnostic clinic for children.
AB  - AIM: To examine parents' personal experiences of a diagnostic clinic for children
      suspected of having autistic spectrum disorder, and to evaluate parental
      satisfaction with the multidisciplinary assessment team at the clinic. METHOD: A
      structured interview schedule was designed to obtain information from parents.
      The questionnaire consisted of set questions divided into four sections using
      closed and open-ended questions. Interviews were conducted in the parents' homes
      over a period of one hour. RESULTS: All families whose child had been diagnosed
      by the clinic were contacted and invited to take part in the study. Of a total of
      24 families, parents from 11 families were interviewed. Responses indicated that
      although many parents were dissatisfied with the clinic, they would continue to
      attend appointments and recommend the clinic to others requiring this service.
      CONCLUSION: The findings of this small-scale study highlight the need for
      improved services for parents and families of children with autistic spectrum
      disorder attending the clinic. Better collaboration between members of the
      multidisciplinary team and parents is required to address the needs of this group
      of people.

PMID- 12205773
TI  - Impaired wound healing in patients with diabetes.
AB  - BACKGROUND: This article reviews a cross-section of literature on wound healing
      and highlights how diabetes mellitus can cause deviations from usual healing
      patterns. CONCLUSION: Nursing interventions can either enhance or delay the
      healing process. Nurses need to understand the defective processes to optimise
      the available healing potential.

PMID- 12205774
TI  - Compression bandaging.
AB  - Compression therapy is an important element to the treatment of venous leg
      ulcers. The factors to be considered when applying compression bandage therapy
      are discussed in detail.

PMID- 12205775
TI  - Warning over rise in HIV infection figures.

PMID- 12205776
TI  - You can make a difference.

PMID- 12205777
TI  - Role of lipid rafts in virus assembly and budding.

PMID- 12205778
TI  - Treatment of arenavirus infections: from basic studies to the challenge of
      antiviral therapy.

PMID- 12205779
TI  - Evaluation of drug resistance in HIV infection.

PMID- 12205780
TI  - Perspectives on polydnavirus origins and evolution.

PMID- 12205781
TI  - Bacteriophage phi 29 DNA packaging.

PMID- 12205782
TI  - Novel vaccine strategies.

PMID- 12205783
TI  - The interaction of orthopoxviruses and interferon-treated cultured cells.

PMID- 12205784
TI  - The potential of plant viral vectors and transgenic plants for subunit vaccine
      production.

PMID- 12205785
TI  - [What kind of surveillance for children with neurofibromatosis type I?].

PMID- 12205787
TI  - [Patterns of use, cannabis beliefs and dependence: study of 159 adolescent
      users].
AB  - OBJECTIVE: To evaluate the connections between the frequency and patterns of
      cannabis use and dependence, and the beliefs linked to cannabis use in a sample
      of adolescents. METHOD: In 2001, 285 high school students (163 boys, 122 girls;
      mean age = 17.5 +/- 1.1 years) completed questionnaires assessing the patterns of
      cannabis use, and the symptoms of dependence and abuse, using a questionnaire
      derived from the Mini International Neuropsychiatric Interview. Cannabis-related
      beliefs were assessed using the Beliefs Questionnaire for Drug Addiction.
      RESULTS: Frequency of subjects who reported having used cannabis during the last
      year was 65.4% of boys and 42.6% of girls. Among users, 53.6% of boys and 39.3%
      of girls were regular users, 10.6% of boys and 7.8% of girls being daily users.
      Almost half of the users reported other means of consumption than "joints", in
      particular water-pipes or "bongs" (34.5% of boys, 26.4% of girls). Among users,
      near of 33% of boys and girls met the criteria for cannabis dependence.
      Dependence was more frequent in users practicing other means of consumption than
      "joints", increasing to 51% for "bong" users. Expectancies of pleasure or relief,
      and permissive beliefs reflecting the perception of cannabis use as risk free
      were higher in users and, particularly, in subjects with cannabis dependence.
      Regression analysis showed that these beliefs were the strongest predictors of
      cannabis use and dependence. Predictors of use in the total sample were
      expectancies of pleasure and permissive beliefs, being a male and the age of the
      subject. Predictors of dependence among users were expectancies of relief,
      frequency of use, and use of other means of consumption than "joints".
      CONCLUSIONS: Cannabis use in adolescents appeared to be characterized by the
      frequency of use, consumption by means other than "joints" and by the frequency
      of dependence. Cannabis use and dependence are linked to expectancies and
      permissive beliefs that could be targeted for prevention and treatment.

PMID- 12205786
TI  - [Effect of racecadotril in the management of acute diarrhea in infants and
      children].
AB  - BACKGROUND: The treatment of diarrhoea relies on the maintenance or restoration
      of hydration with maintenance of an adequate nutritional intake. Racecadotril has
      been shown to reduce the stools output during acute diarrhoea. The present work
      was aimed at measuring the number of emergency department visits for acute
      diarrhoea either the children received racecadotril or not. METHOD: Racecadotril
      and rehydration were compared with rehydration alone in children aged three
      months to three years who had acute diarrhoea and were evaluated in the emergency
      department (ED). The primary end point was the number of medical exams during the
      week after starting treatment. Secondary end points were the number of stools
      during the first 48 hours, the duration of the diarrhoea and the weight on day 7.
      RESULTS: One hundred and sixty-six children were alternatively randomized to the
      treated and the control groups. There was no difference for age, degree of
      dehydration and length of illness before the first visit between the groups.
      Whatever type of rehydration (oral or i.v.), the treated group had a significant
      lower number of stools (p < 0.001) and a faster recovery (p < 10(-9)). The
      children receiving racecadotril needed less additional ED visits for the same
      episode (p < 0.05). There was no difference for the weight-gain on day 7.
      CONCLUSIONS: This study demonstrates the efficacy of racecadotril as adjuvant
      therapy to oral and i.v. rehydration in the treatment of acute diarrhoea and a
      fewer emergency department second visit before recovery.

PMID- 12205788
TI  - [Chiari type I malformation in children: presentation in 34 cases].
AB  - Incidental diagnoses of Chiari I malformation are more and more frequent in pauci
      or asymptomatic children. The value of neurophysiological investigations for
      surgical indications is discussed. OBJECTIVE: To determine clinical presentations
      of Chiari I malformation and relative frequencies of severe and incidental forms,
      and to evaluate the usefulness of neurophysiological investigations for surgical
      indications. METHODS: This retrospective study included 34 patients admitted from
      1984 to 2000, with Chiari I malformation diagnosis in different pediatric
      (intensive care, neurology and neurosurgery) units of a university hospital.
      RESULTS: The clinical presentation was severe (two children died) in four cases
      (12%). Signs of brain stem compression were found in 41% of cases, scoliosis in
      21%, and incidental diagnosis in 26%. The polysomnography, performed in 12 cases,
      showed sleep-apneas in six cases. One child with an incidental diagnosis of
      Chiari I malformation had many sleep-apneas which required a surgical treatment.
      A surgical decompression was performed in 69% of cases, with clinical improvement
      in 77%. CONCLUSION: The high incidence (12%) of severe forms revealing Chiari I
      malformations justifies systematic neurophysiological investigations for the
      initial evaluation and the follow-up of Chiari 1 malformations, including the
      less symptomatic forms.

PMID- 12205789
TI  - [Optic pathway gliomas in neurofibromatosis type I. Longitudinal study of 30
      cases in two multidisciplinary practices].
AB  - The aim of this study was to analyse the outcome of optic pathway gliomas in 30
      children with neurofibromatosis type 1, the indications of treatment, and the
      follow-up and screening protocol. PATIENTS AND METHODS: All patients with a
      minimal two years follow-up (median six years, range two to 19 years), in two
      multidisciplinary consultations of Saint-Vincent-de-Paul (Paris) and Purpan
      (Toulouse) hospitals, were included in the study. In our series, we practiced
      systematic screening MRI in children under six years' of age or with
      neuropsychological deficiency that may imply an unreliable ophthalmological
      examination. RESULTS: Thirty-seven percent (11 patients) had progressive
      ophthalmological signs and were treated, and 63% (19 patients) were not
      progressive. Our study confirmed that most of optic pathway gliomas were stable
      during evolution, but rare cases may have bad prognosis. CONCLUSION: Our study
      supported the importance of close ophthalmological follow-up during childhood for
      which screening methods are discussed. There is a consensus to limit treatment
      for patients with progressive ophthalmological symptoms.

PMID- 12205790
TI  - [Congenital long QT syndrome in newborns].
AB  - The perinatal manifestations of the long QT syndrome are rare, but early
      diagnosis and therapy are necessary to prevent sudden death. CASE REPORTS: A long
      QT syndrome was diagnosed in two neonates who presented with foetal bradycardia.
      In one case, a mutation in the gene KCNQ1 was identified, and a long QT syndrome
      was diagnosed in the mother and two brothers of the neonate. On beta-blocker
      therapy, one infant became free of long QT syndrome related symptoms, but a
      sudden death of the second infant occurred. CONCLUSION: The long QT syndrome
      should be considered in the differential diagnosis of foetal bradycardia. Early
      treatment of the neonate and his family may prevent ventricular arrhythmias and
      sudden death.

PMID- 12205791
TI  - [Severe multiorgan psittacosis in a 10-year-old boy].
AB  - Psittacosis is rare among children and severe cases appear exceptional. We
      describe a child with psittacosis and multiorgan involvement. CASE REPORT: T., a
      ten-year-old boy, was admitted for a prolonged fever associated with meningism.
      Laboratory tests showed an important inflammatory response, mild renal failure
      and coagulation disorders. On admission, the chest X-Ray and the cerebrospinal
      fluid were normal. He rapidly developed shock, acute abdomen, oxygenodependency,
      pneumonia and bilateral pleural effusion. No improvement was observed after 48
      hours of cefotaxime therapy. History revealed the presence of two parrots at
      home. Treatment by intravenous clarithromycin was therefore initiated. Serology
      for Chlamydia psittaci was strongly positive. All symptoms disappeared a few days
      later. CONCLUSION: The case reported was particular for two reasons: severe
      disease with multi-organ involvement and young age of the patient. We emphasize
      the need to search for a history of contact with birds in any case of unexplained
      pneumonia.

PMID- 12205792
TI  - [Brachial plexus paralysis of infectious origin: report of four cases].
AB  - BACKGROUND: Brachial plexus palsy (BPP) may occur after septic osteoarthritis of
      the shoulder. BPP is a rare, well recognized complication. The pathophysiology is
      thought to be either ischemic nerve damage secondary to occlusion of vasa
      nervorum or extrinsic compression. Early diagnosis and treatment of the infection
      are needed. CASE REPORTS: We report the cases of three infants aged less than
      three months and one six-day-old newborn infant who presented with an authentic
      BPP due to an osteoarthritis of the shoulder. The diagnosis of osteoarthritis
      relied on clinical, biological and radiological signs. In one case, the causal
      germ (Enterobacter) was isolated. The diagnosis of the palsy was based on
      clinical signs. EMG performed on one patient, showed signs of abnormal motor
      pattern. Following intravenous antibiotics and percutaneous drainage, all infants
      completely recovered.

PMID- 12205793
TI  - [Massive fetomaternal transfusion after induction of labor by oxytocin].
AB  - Severe fetomaternal transfusions are seldom, but may lead to neonatal morbidity
      or death. CASE REPORT: We report a case of lethal fetomaternal transfusion in
      which a failure to induce labour, at term, can be suspected. COMMENTS: We
      emphasize the need of a close monitoring of the fetal well-being in cases of
      failed induced labour at term.

PMID- 12205794
TI  - [Hematologic manifestations of inborn errors of metabolism].
AB  - Haematological symptoms can be helpful for the diagnosis of metabolic diseases. A
      megaloblastic anemia orientates to folate and cobalamine anomalies when
      associated with homocystinemia and decreased plasma methionine levels, or to
      congenital oroticuria (hypochromia), Pearson syndrome (sideroblasts and
      vacuolisation of precursors) and thiamine transporter abnormality (sideroblasts)
      in the absence of homocystinuria. An hemolytic anemia orientates to anomalies of
      anaerobic glycolysis, heme synthesis, or iron metabolism, and Wilson disease. A
      pancytopenia orientates to organic aciduria, lysinuric protein intolerance,
      mevalonic aciduria and lysosomal storage diseases (Gaucher, Niemann Pick, Wolman)
      when hepatosplenomegaly is present. Uremic hemolytic syndrome and hemophagocytic
      lymphohistiocytosis respectively orientate to B12 anomalies, lysinuric protein
      intolerance, lysosomal storage diseases and organic aciduria.

PMID- 12205795
TI  - [Biphosphonates in children: present and future].
AB  - Biphosphonates are synthetic analogs of the natural pyrophosphate molecule,
      introduced primarily for the treatment of Paget disease of bone. Their main
      mechanism of action consisting in an inhibition of osteoclastic activity is
      critical for treatment of disorders including an increased bone resorption. In
      childhood osteoporosis (especially osteogenesis imperfecta), hypercalcemia and
      heterotopic calcifications are the three main situations in which they have been
      successfully used, with however few follow-up and no controlled studies. The
      evolution of these compounds generating more potent products, given orally, with
      limited effect on bone mineralization should allow an extension of their use in
      pediatric patients. Multicentric studies are now necessary to specify their
      efficacy and guidelines for use in children.

PMID- 12205796
TI  - [Allergic rhinitis in children].
AB  - The diagnosis of allergic rhinitis (AR) in children is mainly based upon history
      which leads to distinguish between seasonal (periodic or intermittent) pollinic
      AR and perrenial (permanent or chronic) AR. The consequences of an AR can be
      severe with major nasal discomfort, repercussion on quality of life and school
      attendance, and impact on facial bone growth. In addition it can be complicated
      by asthma. Specific desensitization is the only treatment which may modify the
      immune response towards allergens. However it must be compared with the other
      treatments including local or general antihistaminic drugs and intranasal
      corticosteroids, the choice resting upon the severity of the symptoms, the
      respiratory repercussion, and the age of the child.

PMID- 12205797
TI  - [Antiepileptics].
AB  - Antiepileptic drugs can be schematically classified according to their spectrum
      of action on generalized or partial epileptic seizures: sodium valproate,
      lamotrigine, benzodiazepines and topiramate are large spectrum molecules which
      are effective in generalized and partial epilepsies. Carbamazepine, vigabatrin,
      gabapentine, tiagabine, phenytoin and phenobarbital are effective in partial
      epilepsies. Ethosuccimide is effective in absence seizures. The main
      characteristics of these different drugs are described and the general principles
      of their prescription are recalled.

PMID- 12205798
TI  - [Conjoined twins of of the caudal parapagus type].

PMID- 12205799
TI  - [Deep venous thrombosis in an adolescent taking oral contraceptives].

PMID- 12205800
TI  - [Reliability and utility of the Apgar score].

PMID- 12205801
TI  - [Obstetrical and neonatal risk associated with teenage delivery in a hospital
      center in Dakar (Senegal)].

PMID- 12205802
TI  - [Estimation of urine specific gravy using dipstick].

PMID- 12205803
TI  - [Ambulatory management of acute diarrhea in infants].

PMID- 12205804
TI  - [Biliary lithiasis in patients with sickle cell anemia. Greek experience].

PMID- 12205805
TI  - [Allergen skin tests. Asthmatic infants and young children].
AB  - Skin tests represent a major tool in the diagnosis of IgE mediated-allergy. The
      main indication is the measure of atopy during infancy and early childhood, as a
      predictive factor of the development of asthma. When atopic eczema is present,
      skin testing can provide a diagnosis of food allergy. Skin tests are easily done,
      without absolute contraindications. The epidemiological knowledge helps to choose
      the allergens to test. The skin-prick test method is well standardized and must
      be rigorous because of the hyporeactivity of the infant skin. Results are always
      confounded with positive and negative control solutions. The interpretation of
      pricks tests must be careful, standing out a clinical allergy (when clinical
      allergic symptoms are presents) from a sensitization (atopy). The predictive
      value of a positive skin test is discussed: predisposition to asthma, association
      with severe asthma, predisposition to acute bronchiolitis during an epidemic of
      respiratory virus. A positive skin test to food allergen would predict a later
      pneumallergen sensitization.

PMID- 12205806
TI  - [Asthma in infants and young children: definitions and epidemiology].
AB  - Asthma of infants and young children (under school age) is a syndrome and not a
      disease. While the definitions given in 1981 by Tabachnik an Levision and by
      Geubelle still hold good, recent epidemiological findings show that several
      situations exist. Less than 20% of asthmatic infants in fact have allergic asthma
      that will persist after the age of 10. Bronchiolitis due to respiratory syncytial
      virus leads to a common variety of asthma. But pre-existing abnormalities of the
      small airways which create favorable conditions for bronchiolitis may also lead
      us to overestimate the sequelae. Prospective follow-up of cohorts of newborns is
      thus very important, and all wheezy children should undergo careful examination
      to exclude "false asthma" and identify "true asthma".

PMID- 12205807
TI  - [Inflammatory markers in infant asthma].
AB  - After a brief review of airway inflammation mechanisms, the main results
      concerning the studies on airways inflammation in wheezing infants are commented.
      Infantile asthma differed from adult asthma by a predominance of neutrophils in
      airways, but less eosinophils or mastocytes. However, the presence of eosinophil
      or mastocyte markers does not allow to exclude a contribution of eosinophils in
      infantile wheeze. Studies on macrophages at cell level showed that a potent
      inflammation from macrophages exists in asymptomatic asthmatic infants.
      Lymphocyte subsets studies demonstrated a modulation of CD8 in these infants,
      suggesting the role of lymphocytes and the contribution of viruses in the
      pathophysiology of the disease. Lastly, the measurement of various mediators in
      airways confirmed that airway inflammation is present in infantile wheeze.

PMID- 12205808
TI  - [Asthma in infants: clinical aspects].
AB  - The diagnosis of asthma in infants is primarily clinical. It is based on the
      recurrence of episodes of bronchial obstruction that may vary in severity and in
      their manifestations. In its typical form, asthma in infants differs little from
      that observed in older children and combines attacks of dyspnoea with coughing
      and wheezing without intercritical clinical disorders. Serious forms are
      characterized by more frequent attacks, impairment of the patient's general
      state, and reduced efficacy of treatment. In some infants, manifestations may
      differ from the usual clinical picture with predominant coughing attacks or
      chronic recurrent episodes of bronchial obstruction. Relating these non-specific
      clinical signs to asthma requires a detailed history-taking, thorough physical
      examination, and routine investigations. In all cases, establishing the diagnosis
      of asthma in young children warrants the use of specific treatment both during
      attacks and as means of preventing their occurrence.

PMID- 12205809
TI  - [Differential diagnosis of asthma in infants and young children].
AB  - Although when an infant or a young child presents with persistent or recurrent
      wheezing, the probability of asthma is high, one must remain very careful in
      order not to miss an other etiology. Except for the chest X ray with inspiratory
      and expiratory studies that is mandatory, the other evaluations should be based
      on a careful interview and clinical examination. Fiberoptic bronchoscopy may be
      indicated each time there is a doubt on foreign body aspiration or
      tracheobronchomalacia.

PMID- 12205810
TI  - [Role of viral infections and Chlamydia pneumoniae and Mycoplasma pneumoniae
      infections in asthma in infants and young children. Epidemiologic study of 118
      children].
AB  - Wheezing associated with upper respiratory tract infections is common in
      children. Using conventional techniques (viral culture and immunofluorescence)
      and molecular techniques (PCR), we studied the prevalence of viral, Chlamydia
      pneumoniae (CP) and Mycoplasma pneumoniae (MP) infections in 118 children
      hospitalised for acute asthma exacerbation. A virus was identified by
      conventional techniques in 40 of the 118 nasal swabs (34%), while PCR allowed
      identification of virus CP and MP in 80 samples (68%). Combination of both
      techniques allowed identification of an infectious agent in 91 cases (77%). More
      than one agent was isolated in 15 cases (23%). Rhinovirus (RV) (45%) were
      prevalent, followed by respiratory syncytial virus (RSV) (28%) and enterovirus
      (8.5%). RV and RSV have a similar prevalence (42% and 36% respectively) before
      two years of age, as compared with 66% and 27% respectively in older children. CP
      and MP were identified by PCR in only 6 cases. Molecular techniques of
      identification demonstrated a clear advantage in sensitivity compared with
      conventional techniques. The high prevalence of RV and RSV infections is
      remarkable, while CP and MP do not seem particularly involved in children acute
      asthma exacerbation.

PMID- 12205811
TI  - [From bronchiolitis to asthma].
AB  - Relationships between lower respiratory diseases with wheezing during infancy and
      asthma at school-age remain debatted. Indeed, although epidemiologic studies show
      that wheezy infants most often become asymptomatic before entry to school, they
      also demonstrate that severe bronchiolitis during infancy is a significant risk
      factor for persistence of wheezing episodes at school-age. One of the most
      important factors demonstrated to enhance the risk for persistence of asthma is
      an early allergic sensitization.

PMID- 12205812
TI  - [Risk factors: environment, tobacco smoke].
AB  - Environmental factors are usually considered as risk factors for increase of
      asthma prevalence. They may act isolately but are frequently associated. They act
      either directly by inducing asthma or more likely by increasing allergenic
      sensitization. Geographic situation is a well known risk factor. Important
      differences are noted between countries. The western lifestyle is evocated,
      including type of alimentation, small size of siblings, increased allergen
      exposure in houses. Intrauterine environment may play a role, particularly
      tobacco smoke during pregnancy and its respiratory effects on infant. Maternal
      allergenic exposure during pregnancy is an important factor because of
      maternofetal immunologic interactions. Outdoor pollution acts by enhancing
      bronchial responsiveness, allergenic sensitization and worsening respiratory
      diseases. Its effect is probably less important in infants and small children who
      are living indoor most of the time. Infections seems to have a complex action.
      Some virus, including respiratory syncytial virus, act to induce asthma or
      sensitization. Other type of infections (viral ou microbial) have a protector
      effect. Exposure to tobacco smoke, particularly maternal smoking, is identified
      in all studies, as one of the most important factors to be considered in
      childhood asthma. Exposure to allergen increases the risk of sensitization. Its
      direct responsibility to induce asthma is not established. Some of recent studies
      are suggesting the concept of a protective effect of early exposure. As far as
      preventive intervention is concerned, the recognition of these factors is
      important to limit the prevalence of childhood asthma.

PMID- 12205813
TI  - [The beta-2-agonists in asthma in infants and young children].
AB  - beta 2-agonists, by inducing a fast and long relaxation of the bronchial smooth
      muscle, are considered as the more potent bronchodilators. beta 2-receptors are
      present from the 16th gestational week, explaining a possible bronchial response
      in the youngest children. beta 2-agonists do not induce any bronchodilator
      response in healthy children. Short-acting beta 2-agonists (salbutamol or
      albuterol, terbutaline) are indicated for asthma attacks, as needed in chronic
      asthma, and for prevention of symptoms during effort. They are safe and secure.
      The more efficient route of administration in preschool children is pressurized
      metered-dose inhaler used with a spacer device. Therefore, whatever the route of
      inhalation chosen (inhalation, injection, or continuous nebulization in acute
      asthma attack), more specified indications and doses are needed in young
      children. Long-acting beta 2-agonists (formoterol, salmeterol) are not authorized
      in France in children under 4 to 5 years of age depending on the drug used.
      Because of new oral formulations and recent considerations about their use in
      asthma attack, instead of short-acting beta 2-agonists, their indication in
      preschool asthmatic children might be reconsidered.

PMID- 12205814
TI  - [Inhaled corticosteroids in asthma in infants and young children].
AB  - Inhaled corticosteroids have become the mainstain in the treatment of asthmatic
      children and adults. Asthma in infancy and early childhood is a heterogeneous
      condition, with different disease phenotypes and outcome. However, rationale data
      justifying the use of inhaled corticosteroids in toddlers and preschool children
      are now available. We recall the results of controlled trials studying the
      efficacy of inhaled corticosteroids, their potential side-effects, and their
      actual indications and modalities of prescription.

PMID- 12205815
TI  - [Role of gastroesophageal reflux in asthma in infants and young children].
AB  - Gastroesophageal reflux (GER) occurs more frequently in asthmatic children than
      in general population. Esophageal pH recording data may be somewhat particular.
      The debate on GER increasing bronchial obstruction or GER being a parallel
      phenomenon remains controversial. Hypotheses are: acid microaspirations giving
      bronchospasm, vagally-transmitted reflex, or more probably coexisting phenomena.
      Pulmonary contamination is rarely seen during esophageal scintigraphy. Asthma
      symptoms are rarely clearly correlated to acid reflux episodes in pH-recording
      studies. However the esophageal acid infusion test may increase bronchial
      obstruction in adult asthmatics. Basically, when should one seek GER in asthmatic
      children? Many authors keep this for asthmatic children not responding to
      conventional treatment, also keeping in mind that GER-specific therapy efficacy
      is often difficult to appreciate in such patients. Briefly, one may speculate
      that GER improves with bronchodilator treatment in most cases.

PMID- 12205816
TI  - [Asthma and food allergy: report of 163 pediatric cases].
AB  - The prevalence of food as a cause for asthma is not well known. The aim of this
      study was to define with standardized tests the incidence of food-induced asthma,
      the distribution of foods allergens in asthmatic children with food allergy. The
      study was carried on 163 asthmatic children with food allergy followed during
      average of 5.5 years. Asthma has been identified with pulmonary function tests
      (reversibility of FEV1 to bronchodilators) and food allergy has been documented
      by double-blind placebo-controlled food challenge (DBPCFC). Familial atopic
      disease was found in 148 children (90.7%). Inhalant sensitization was documented
      in 132 children (81%). Positive DBPCFC were observed in 250 of 385 challenges
      (65%) carried on these 163 children. The most frequent offending foods were,
      sometimes in association, peanut (30.6%), egg (23.1%), cow's milk (9.3%), mustard
      (6.9%), codfish (6%), shrimp (4.5%), kiwi fruit (3.6%), hazelnut (2.7%), cashew
      nut (2.1%), almond (1.5%), garlic (1.2%). Symptoms occurring during DBPCFC were
      cutaneous (143 cases, 59%), respiratory symptoms (58 cases, 23.9%),
      gastrointestinal symptoms (28 cases, 11.5%) and 15 anaphylactic shock (6.1%).
      Respiratory symptoms were oral allergy syndrome in 13 cases (5.3%),
      rhinoconjunctivitis in 15 cases (6.1%), asthma in 23 cases (9.5%). Only seven of
      these children had asthma only (2.8% of cases). The prevalence of asthma induced
      by food allergy is low. In our study, asthma induced by food allergy concerned
      9.5% of cases and asthma alone was identified in only 2.8% of cases. We observed
      new food allergens associated with respiratory symptoms such as kiwi fruit, tree
      nuts (hazelnut, cashew) and spices. Diagnosis relied upon data obtained from
      history, skin prick-tests and specific IgE. Oral food challenge is the corner
      stone of the diagnosis. Asthma induced by food allergens is potentially severe
      leading to prescribe to these patients a first aid kit with bronchodilators and
      epinephrine auto-injectors.

PMID- 12205817
TI  - [Asthma in infants and young children. Prevention, challenge of the 21st
      century?].
AB  - Many studies have been dedicated to the prevention of infant and childhood asthma
      in recent years. Primary prevention begins during intra uterine life (maternal
      smoke, diet, allergen exposure). During the first year of life, prolonged
      breastfeeding has been found to be a protective factor against the development of
      allergy and asthma. The role of infections and lifestyle is controversial and it
      is not clear whether these factors reduce or increase the risk of asthma.
      Environmental measures such as avoidance of tobacco smoke and reducing allergens
      exposure must be recommended to infants with high risk of asthma.

PMID- 12205818
TI  - [Inhalers and nebulizers in the children].
AB  - Inhaled way is the most efficient method to deliver drugs for the treatment of
      respiratory diseases. Pulmonary deposition depends upon the inhalation system and
      technique. The evaluation of the drug deposition is difficult, particularly in
      children. Because of irradiation, scintigraphic studies which permit the best
      approach of the pulmonary deposition are rare in children. Various inhalation
      systems are available: nebuliser, metered-dose inhaler with or without spacer
      device, dry powder inhaler. Whatever the system used, the control of asthma will
      be only possible with the regular evaluation of the child inhalatory technique.

PMID- 12205819
TI  - The status of physiologists and physiology at US medical Schools.

PMID- 12205820
TI  - Impact factors: arbiter of excellence?

PMID- 12205821
TI  - Treatment compliance and outcome in obsessive-compulsive disorder.
AB  - Exposure and ritual prevention (EX/RP) is an effective treatment for obsessive
      compulsive-disorder (OCD), although it is neither universally nor completely
      helpful. Compliance with EX/RP treatment procedures has been linked theoretically
      to posttreatment outcome, yet empirical exploration of this relationship has been
      insufficient. In this study, therapists were asked to rate the treatment
      compliance of 28 consecutive patients who received EX/RP on a fee-for-service
      basis. Results indicated that understanding the treatment rationale and
      compliance with in-session and homework exposure instructions, but not with
      ritual prevention and self-monitoring of rituals, was significantly related to
      posttreatment OCD symptom severity. Clinical implications of these findings and
      future directions in treatment compliance research with OCD patients are
      discussed.

PMID- 12205822
TI  - Positive parenting and child psychosocial adjustment in inner-city single-parent
      African American families. The role of maternal optimism.
AB  - The primary purposes of this study were to examine whether maternal optimism is
      related to positive parenting and child adjustment and whether it contributes
      beyond maternal depressive symptoms to our understanding. The participants were
      141 African American single mothers and one of their children. Findings revealed
      that maternal optimism was associated with positive parenting and this
      association was only partially mediated by maternal depressive symptoms. Maternal
      optimism was not associated with child psychosocial adjustment, but positive
      parenting was associated with lower levels of both internalizing and
      externalizing difficulties. The utility of understanding the link between
      maternal optimism and parenting for prevention and intervention efforts aimed at
      enhancing quality of life and subsequent child adjustment is discussed, as well
      as directions for future research on maternal optimism.

PMID- 12205823
TI  - Assessment and treatment of vocal tics associated with Tourette's syndrome.
AB  - A functional analysis suggested that a young man's vocal tics were maintained by
      automatic reinforcement. A preference assessment was conducted to identify
      stimuli that effectively competed with the occurrence of vocal tics. When used as
      components of a reinforcement-based intervention, however, these stimuli were
      ineffective at reducing the occurrence of vocal tics. Observations conducted in a
      naturalistic context led to the hypothesis that variations in tics were
      associated with body positioning. Thus, an additional analysis was conducted to
      determine if vocal tics occurred less when the participant was lying down versus
      when he was seated upright. Results suggested that a combination of procedures
      might be useful in developing idiosyncratic interventions for automatically
      reinforced problem behavior, such as vocal tics.

PMID- 12205824
TI  - The effects of training parents in functional behavior assessment on problem
      identification, problem analysis, and intervention design.
AB  - In this study, parents were trained in four sessions to identify problems,
      conduct a functional assessment, and design an appropriate intervention based on
      the function of the problem behavior. First, parents were trained to
      operationally define problem behaviors, given examples of consequences, and
      discussed the functions of behavior. Second, parents were given examples of
      antecedents and discussed replacement behaviors. Third, procedures to increase
      appropriate behaviors were discussed. Fourth, procedures to decrease
      inappropriate behaviors were discussed. Prior to the first session and after each
      session, parents watched a videotaped vignette of a child exhibiting a behavior
      problem and completed a Problem Identification Questionnaire, Problem Analysis
      Questionnaire, and Intervention Design Questionnaire. A repeated-measures ANOVA
      was used to test for significant differences on each of the dependent variables.
      Results indicated that parents' scores on each of the measures improved
      significantly. Limitations, future research ideas, and implications for school
      psychologists and other professionals are discussed.

PMID- 12205825
TI  - An analysis of physical guidance as reinforcement for noncompliance.
AB  - Physical guidance is a strategy commonly used for noncompliance. In two
      experiments, we evaluated reinforcing effects of physical guidance. Experiment 1
      include three individuals with developmental disabilities who were noncompliant
      with tasks. Anecdotal observations indicated physical contact was highly
      reinforcing, and a functional analysis identified attention as a reinforcer for
      problem behavior. Two conditions compared physical guidance following
      noncompliance and no physical guidance following noncompliance. Results showed
      noncompliance increased for all three participants when physical guidance
      followed noncompliance. The second experiment empirically evaluated the function
      of noncompliance prior to examining the effect of physical guidance on
      noncompliance. A functional analysis, conducted with two participants, indicated
      noncompliance served an escape function for one and an attention function for the
      other. Comparisons of physical guidance and no physical guidance indicated
      physical guidance resulted in decreased noncompliance for the participant with an
      escape function but increased noncompliance for the participant with an attention
      function.

PMID- 12205826
TI  - The efficacy of using a personal stereo to treat auditory hallucinations.
      Preliminary findings.
AB  - This article presents preliminary findings from the first participant to complete
      an experiment assessing the efficacy of the personal stereo in treating auditory
      hallucinations. O.C., a 50-year-old woman, took part in a controlled treatment
      trial in which 1-week baseline, personal stereo, and control treatment
      (nonfunctioning hearing aid) stages were alternated for 7 weeks. The Positive and
      Negative Syndrome Scale, Clinical Global Impression Scales, Beliefs About Voices
      Questionnaire, Rosenberg Self-Esteem Scale, and Topography of Voices Rating Scale
      were used. The personal stereo led to a decrease in the severity of O.C.'s
      auditory hallucinations. For example, she rated her voices as being fairly
      distressing during baseline and control treatment stages but neutral during
      personal stereo stages. A slight decrease in other psychopathology also occurred
      during personal stereo stages. Use of the personal stereo did not lead to a
      decrease in self-esteem, contradicting suggestions that counterstimulation
      treatments for auditory hallucinations may be disempowering.

PMID- 12205827
TI  - The Coolidge Personality and Neuropsychological Inventory for Children (CPNI).
      Preliminary psychometric characteristics.
AB  - This study describes the preliminary psychometric characteristics of a new parent
      as-respondent assessment tool, the Coolidge Personality and Neuropsychological
      Inventory for Children (CPNI). The CPNI contains 200 items answered on a 4-point
      Likert-type scale. The CPNI has a three-fold purpose: (a) to assess the 12
      personality disorders according to the criteria on Axis II and Appendix B of the
      Diagnostic and Statistical Manual of Mental Disorders; (b) to assess
      neuropsychological dysfunction, including Attention-Deficit/Hyperactivity
      Disorder, Mild Neurocognitive Disorder, executive function deficits, and other
      related symptoms; and (c) to measure some Axis I diagnoses including Separation
      Anxiety Disorder, Oppositional Defiant Disorder, depression, and general anxiety,
      as well as other clinical syndromes. The scale reliabilities and test-retest
      reliabilities were moderate to high, and construct validity was good, which
      supports further research with the inventory.

PMID- 12205828
TI  - Use, quality, and outcomes of care for mental health: the rural perspective.
AB  - This review synthesizes empirical research in rural mental health services to
      identify current research priorities to improve the mental health of rural
      Americans. Using a conceptual framework of the multiple determinants of use,
      quality, and outcomes, the authors address (1) how key constructs are
      operationalized, (2) their theoretical influence on the care process, (3)
      reported differences for nonmetropolitan and metropolitan individuals or within
      nonmetropolitan individuals, (4) salient issues rural advocates have raised, and
      (5) key research questions. While the authors recognize that rurality is a useful
      political umbrella to organize advocacy efforts, they propose that investigators
      no longer employ any of the multiple definitions of the term in the literature as
      even intrarural comparisons have not provided compelling evidence about the
      underlying causes of observed outcomes differences. Until these underlying causes
      have been identified, it is difficult to determine which components of the
      nonmetropolitan service system need to be improved.

PMID- 12205829
TI  - Patterns of health insurance coverage among rural and urban children.
AB  - Despite the potential for the State Children's Health Insurance Program to
      improve the health care coverage of rural children, the expansion of public
      health insurance to children in rural areas may be hampered by a lack of
      understanding about the patterns of insurance coverage they experience. This
      study uses the Census Bureau's 1993-1996 panel of the Survey of Income and
      Program Participation to evaluate differences in the duration of, and in their
      entry into and exit from, uninsured spells. While the average duration of new
      spells was shorter for rural children and most regained coverage quickly, rural
      children were also more likely than urban children to experience protracted
      spells of uninsurance. Moreover, rural children were more likely than urban
      children to move between public and private coverage. These findings have
      important implications for designing insurance expansion programs and outreach
      strategies to effectively enroll and retain rural children.

PMID- 12205830
TI  - Measuring patients' trust in their primary care providers.
AB  - Existing scales to measure trust in physicians have differing content and limited
      testing. To improve on these measures, a detailed conceptual model was
      constructed and a large item pool (n = 78) was generated following a detailed
      conceptual model and expert review. After pilot testing, the best-performing
      items were validated with a random national sample (n = 959) and a regional
      sample of HMO members (n =1,199). Various psychometric tests produced a 10-item
      unidimensional scale consistent with most aspects of the conceptual model.
      Compared with previous scales, the Wake Forest physician trust scale has a
      somewhat improved combination of internal consistency, variability, and
      discriminability. The scale is more strongly correlated with satisfaction, desire
      to remain with a physician, willingness to recommend to friends, and not seeking
      second opinions; it is less correlated with insurer trust, membership in managed
      care, and choice of physician. Correlations are equivalent with lack of disputes,
      length of relationship, and number of visits [corrected].

PMID- 12205832
TI  - Rating outlets for health care management research: an update and extension.
AB  - The ongoing discussion of our intellectual community requires that occasionally
      an effort be made to value the outlets for our research and erect guideposts for
      our colleagues to signal important contributions to our discipline. This study
      extends previous work through a survey sent to 1,254 academics involved in health
      care management research that asked them to rate 54 potential outlets for their
      research. Ratings were made on journal knowledge, quality, and relevance. Two
      survey waves resulted in 389 responses (adjusted response rate 37.8 percent). For
      quality and relevance, journal rankings were separated into A, B, and C
      categories. The results correlated strongly with the two previous studies in this
      area. This study extends previous research and provides a categorization of
      journals on knowledge, quality, and relevance that may assist in faculty
      performance evaluation and identification of appropriate outlets for manuscripts.

PMID- 12205831
TI  - Effect of CAHPS performance information on health plan choices by Iowa Medicaid
      beneficiaries.
AB  - This evaluation tested if Consumer Assessment of Health Plans Study (CAHPS)
      information on plan performance affected health plan choices by new beneficiaries
      in Iowa Medicaid. New cases entering Medicaid in selected counties during
      February through May 2000 were assigned randomly to experimental or control
      groups. The control group received standard Medicaid enrollment materials, and
      the experimental group received these materials plus a CAHPS report. We found
      that CAHPS information did not affect health plan choices by Iowa Medicaid
      beneficiaries, similar to previously reported findings for New Jersey Medicaid.
      However, it did affect plan choice in an earlier laboratory experiment. The value
      of this information may be limited to a subset of receptive consumers who
      actively study information received, even then only when (1) ratings of available
      plans differ greatly, (2) ratings differ from prior beliefs about plan quality,
      and (3) reports are easy to understand.

PMID- 12205833
TI  - Breast intentions.

PMID- 12205834
TI  - Over the edge. Interview by Lynne Wallis.

PMID- 12205835
TI  - The cost of care.

PMID- 12205836
TI  - Alternative measures.

PMID- 12205837
TI  - Barriers to healthy eating in the nursing profession: Part 1.
AB  - AIM: The aim of this study commissioned by the NHS Executive North West was to
      identify the main areas of the nurse's working environment that prevent healthy
      eating, to ascertain if nurses have enough nutritional knowledge to make informed
      choices, and to review sources, availability and quality of food provided for
      nursing staff. METHOD: A purposive sample size of 126 nurses from across eight
      healthcare sites in the North West region completed questionnaires. RESULTS:
      Shift patterns and failure to take breaks were identified as the two main
      barriers to healthy eating by respondents. However, satisfaction with food on
      offer and a supportive environment were also identified as important influences.
      CONCLUSION: Several recommendations were made as a result of the study. Ideally,
      nurses should take regular breaks. Food should carry nutritional labelling and
      nutritional information should be displayed at healthcare sites in a more
      imaginative and innovative way. More refrigerated vending machines with a
      selection of healthier options should be supplied. Packed lunches or plated
      salads obtainable from restaurants by evening and night-shift nurses should be
      offered, in addition to a better selection of sandwiches and other food choices
      outside the hours of 9 am to 5 pm, Monday to Friday. Nurses should be encouraged
      to drink the recommended amount of eight glasses of water per day (Health and
      Fitness Tips 2000) by providing adequate water dispensers. The possibility of
      having separate catering facilities for staff who wish to avoid patients and
      visitors during breaks should be explored.

PMID- 12205838
TI  - Practice development: individualized care.
AB  - This article describes the development of a person-centred approach to working
      with older people. The main focus is on developing the ward leader as a key
      facilitator of practice development work. This process was enabled through
      external facilitation of the role and project management. The stages of the
      project work are outlined using an established practice development framework,
      which ensured a systematic approach to the change process. Registered nurses
      developed their skills and knowledge in clinical leadership and by the end of the
      project, nursing care had moved away from meeting the physical needs of the
      patients only, to a more individualized approach to patient care.

PMID- 12205839
TI  - Myocardial infarction: Part 1.
AB  - Informed nursing care is crucial in effective treatment and rehabilitation of the
      patient following MI. The National Service Framework for Coronary Heart Disease
      should be integrated into nursing practice.

PMID- 12205840
TI  - Practice what you preach. Interview by Frances Pickersgill.

PMID- 12205841
TI  - At a stroke.

PMID- 12205842
TI  - Healing old wounds. Interview by Catharine Sadler.

PMID- 12205843
TI  - Why do you want this job? Interview by Renate Thome.

PMID- 12205844
TI  - Blurred vision.

PMID- 12205845
TI  - Expectations of newly qualified nurses.
AB  - AIM: This study offers an overview of the concerns and expectations of newly
      qualified staff at the beginning of their careers. METHOD: A focus group was used
      to question nine newly qualified nurses about concerns and expectations in
      relation to their new role. The information obtained from the focus group was
      transcribed. RESULTS: The themes highlighted were role acquisition, separation
      from student status, transition to staff nurse status and integration into the
      profession. Discussion in the focus group led to the recommendation of guidelines
      to help support the role. CONCLUSION: Action is recommended to promote retention
      of this particular staff group.

PMID- 12205846
TI  - Implementing evidence-based practice in clinical situations.
AB  - Many nurses in a variety of clinical settings are facing the challenges posed by
      incorporating evidence-based practice in health care. Some of the steps involved
      in implementing evidence-based care in clinical practice are discussed and a two
      step framework to assist practitioners in implementing evidence-based practice is
      outlined. Factors such as the relevance of specific guidelines or research,
      generalisability of research findings, the strength of the evidence relative to
      the risks and benefits of treatment, and patient preferences are discussed in
      terms of evidence-based decision making.

PMID- 12205847
TI  - Food safety.
AB  - Food poisoning remains one of the most common causes of illness worldwide. Nurses
      are well placed to educate patients on food safety and provide balanced arguments
      about pesticides, genetic modification and BSE.

PMID- 12205848
TI  - AIDS care takes its toll on staff.

PMID- 12205849
TI  - Equal opportunity.

PMID- 12205850
TI  - Don't shoot the messenger.

PMID- 12205851
TI  - Power struggle.

PMID- 12205852
TI  - Getting there.

PMID- 12205853
TI  - Nurse training has lost its way.

PMID- 12205854
TI  - Waiting for ages.

PMID- 12205855
TI  - Looking at the stars.

PMID- 12205856
TI  - Living with chronic pain: the patient's perspective.
AB  - AIM: The aim of this study is to investigate patients' perceptions and
      experiences of chronic pain management before and after attending pain services.
      METHOD: A sample of 245 patients with chronic pain, who attended specialist pain
      services in 11 UK hospitals, were interviewed using a structured questionnaire.
      Patients' ages ranged between 23 and 86 years (median 51 years), and the duration
      of pain ranged between six months and 57 years (median five years). RESULTS:
      Patients reported that pain had had a profound effect on their lives, restricting
      daily living and leisure activities. 33 per cent (81) were classified as
      medically disabled. Patients' perceptions and attitudes to the management of
      chronic pain varied. Their main concern was that, although they wanted a specific
      diagnosis, they were often not given a reason for their chronic pain. CONCLUSION:
      Pain management requires a significant amount of input by health professionals.
      Patients wanted advice on the best techniques to help them cope with chronic
      pain. Most patients had previously tried many different pain treatments to obtain
      short-term pain relief. One third of patients had waited up to four months for
      their initial pain assessment at the pain service. Once referred to specialist
      pain services, patients were satisfied with their care. Almost half (47 per cent,
      115) of the interviewees reported that their pain had improved. As chronic pain
      has a profound effect on patients' lives, it is important that early diagnosis,
      treatment and referral to appropriate specialists is given high priority. This
      study has raised the awareness and understanding of an important, but often
      misunderstood area.

PMID- 12205857
TI  - A collaborative approach to urgent mental health referrals.
AB  - The National Service Framework for Mental Health was launched in October 1999 and
      detailed the standards required for an effective and robust service (DoH 1999).
      Within North Solihull, a quick response initiative for urgent referrals to the
      mental health team has been in operation for the past five years. It is a nurse
      led service that appears to meet some of the standards set, including
      collaboration with primary care and suicide prevention. This article identifies
      the benefits of a nurse-led service to combat the growing need for urgent
      assessment. It also discusses the need for specific mental health practitioner
      involvement at the point of referral. Particular reference is made to clients in
      crisis and with suicidal ideation. Important liaison at the interface between
      primary and secondary care is presented, for the benefit of this client group and
      effective alleviation of referrer anxiety.

PMID- 12205858
TI  - Enquiry-based learning: an introductory guide.
AB  - Enquiry-based learning uses real life situations to analyse and possibly refine
      nursing practice. Bob Price discusses the process.

PMID- 12205859
TI  - Women on the move. Interview by Frances Pickersgill.

PMID- 12205860
TI  - [Classification distribution and medicinal sorts of endemic plants in Anhui
      province].
AB  - OBJECTIVE: To explore the natural resources of endemic medicinal plants in
      Anhuei, for reference in regional study of Chinese medicines. METHOD:
      Investigating the natural resources of medicinal plants in Anhuei and collating
      and studying the findings. RESULT AND CONCLUSION: There are 109 species of 37
      families, of which Aristolochiaceae, Ranunculaceae, Crassulaceae, Cucurbitaceae,
      Labiatae, Liliaceae and Berberidaceae, Compositae, Orchidaceae are of greater
      medicinal value.

PMID- 12205861
TI  - [Studies on identification of yinchaihu by UV and IR].
AB  - OBJECTIVE: To study the identification of nine species of Yinchaihu derived from
      four genera of Caryophyllaceae, namely, Stellaria dichotoma var. lanceolata, St.
      dichotoma var. dichotoma, Arenaria juncea, A. capillaris var. glandulifera,
      Silene fortunei, Si. jenisseensis, Gypsophila pacifica, G. oldhamiana and G.
      licentiana. METHOD: UV and IR of alcohol extraction. RESULTS: The UV and IR
      spectra of these 9 plant roots have some difference. CONCLUSION: St. dichotoma
      var. lanceolata specified in the Chinese Pharmacopoeia can be distinguished from
      the other plants and all these 4 genera can be differentiated from one another by
      both UV and first derivative spectra. The genus Stellaria can be identified from
      the other 3 genera by IR.

PMID- 12205862
TI  - [RAPD analysis of germplasm in "baizhi"].
AB  - OBJECTIVE: To analyse the germplasm in Baizhi. METHOD: Using 12 random primers,
      over seventeen individuals' RAPD were detected in four populations from wild
      Baizhi (Angelica dahurica), Qi Baizhi and Hang Baizhi. RESULTS: A total of 40
      loci were amplified, 26 of which were polymorphism(65%). The PPS values of Hang
      Baizhi and Qi Baizhi indicate their low levels of genetic diversity. According to
      the RAPDinstance analysis, the genetic distance(0.16) between Qi Baizhi and Hang
      Baizhi is shorter than that of the individuals of the populations of Qi Baizhi
      and Hang Baizhi, and all of these genetic distances are shorter than those
      between wild Baizhi and Hang Baizhi(Qi Baizhi). CONCLUSION: Hang Baizhi- and Qi
      Baizhi belong to the same taxon, which is different from the wild Baizhi.

PMID- 12205863
TI  - [Seed germinative characteristics and embryo development of Schisandra chinensis
      (Turcz.) Bail].
AB  - OBJECTIVE: To detect the germinative character of S. chinensis seeds. METHOD:
      Using low temperature and gibberellin treatment. RESULT: The breach rate of seeds
      was increased by both low temperature and gibberellin, but the breach on
      different seeds appeared untidy, which showing a character. The embryo
      development is normal before breaching and increased in volume rapidly after
      breaching. CONCLUSION: The bypoplasia of embryos is not the primary reason for
      long dormancy of the seeds.

PMID- 12205864
TI  - [Comprehensive evaluation and practical confirmation on processing technology of
      Daphne genkwa Sieb. et Zucc].
AB  - OBJECTIVE: To investigate the effect of five processing methods for D. genkwa.
      METHOD: Comparing the pharmacodynamic and toxic parameters and related chemical
      constituents of the processed products with those of crude D. genkwa and vinegar
      processed D. genkwa recorded in Chinese Pharmacopoeia. THE RESULT: The vinegar
      stir-fry method was the best. One hundred kilograms of crud D. genkwa was evenly
      mixed with 30 kg vinegar diluted in 60 kg water and moistened in a closed
      container for an hour, then put into a drug-parching machine to get nearly dry
      with slow fire wenhuo and taken out timely. CONCLUSION: Three repetitions of
      pilot production have shown that the technology is simple, easy to operate and of
      good reproducibility, and thus can be used in the production of D. genkwa in
      slice form.

PMID- 12205865
TI  - [A study on major chemical components of Uvaria grandiflora].
AB  - OBJECTIVE: To make clear the chemical constituents of Uvaria grandiflora
      (Annonaceae). METHODS: Purification was performed using sephadex LH-20 permeation
      and silica gel chromatography. Structures of the purified components were
      determined on the basis of 1H, 13C NMR analysis and also by comparison with those
      of authentic compounds. RESULTS: Two major triterpenes, suberosol and lupeol,
      were identified. CONCLUSION: This paper is the first report on the identification
      of suberosol and lupeol from the gunus Uvaria.

PMID- 12205866
TI  - [Chemical constituents of Saururus chinensis (Lour.) Bail].
AB  - OBJECTIVE: To search for the active chemical constituents of Saururus chinensis.
      METHOD: 95% ethanol extracts from the aerial part of Saururus chinensis was mixed
      with silica gel, and then eluted with petroleum ether, ethyl acetate and
      methanol. On the basis of physicochemical properties and spectroscopic analysis,
      structures of the compounds obtained were identified. RESULTS: Eight compounds
      were isolated from the ethyl acetate and methanol parts, and identified as
      aristolactam A II(I), daucosterol(II), hyperoside(III), isoquercitrin(IV),
      quercitrin(V), quercitin-3-O-beta-D-glucopyranosyl(1-->4)-alpha-L
      rhamnopyranoside(VI), ellagic acid(VII) and corilagin(VIII) respectively.
      CONCLUSION: Compounds I, II, VI, VII and VIII were found from this plant for the
      first time.

PMID- 12205867
TI  - [Determination of isofraxidin in Sarcandra glabra (Thunb.) Nakai by HPLC].
AB  - OBJECTIVE: To establish a method for the determination of isofraxidin in
      Sarcandra glabra. METHOD: Using HPLC with mu-Bondapak C18 column, acetonitrile 
      0.1% phosphoric acid solution(20:80) as mobile phase and detection wavelength at
      344 nm. RESULT: The recovery and RSD were 98.1% and 1.9% (n = 5) respectively.
      CONCLUSION: This method is rapid, simple and accurate, thus may be used for the
      quality control of this drug.

PMID- 12205869
TI  - [Inhibitory effect of paeonol on experimental atherosclerosis in quails].
AB  - OBJECTIVE: To study the effect of paeonol on experimental atherosclerosis in
      quails caused by high lipid feeding. METHOD: The effects of oral administration
      of 300 and 600 mg/kg of paeonol on lipid levels in serum, hemorrheology and
      aortic intimal abnormalities were investigated. RESULT: Paeonol decreased TC, TG,
      LDL, vLDL, APOB100 levels in serum and TC levels in aorta and liver. The ratios
      of HDL/TC, HDL2/HDL3, apoA1/apoB100 were elevated. In addition, the drug reduced
      the whole blood viscosity, Plasma viscosity and plasma fibrinogen, and inhibited
      erythrocyte aggregation. CONCLUSION: Oral administration of paeonol can reduce
      the development of atherosclerosis.

PMID- 12205868
TI  - [Antihypertensive study of xingnao qingxuan recipe].
AB  - OBJECTIVE: To observe the effect of decreasing blood pressure of Xingnao Qingxuan
      Casuples. METHOD: The blood pressure in normal and anesthetised cats was examined
      with direct method, the blood pressure in the conscious SHR was obtained by
      indirect method. RESULTS: Duodenuos administration(id) of XQC of 2.8 g/kg
      produced a decrease of blood pressure in normal cats; XQC of 1.4, 2.8 and 5.6
      g/kg once a day for 14 days produced a dose-dependent reduction of blood pressure
      in SHR, 3-4 days after administration the blood pressure returned to the level
      before but the change was not significant. With gastric administration of XQC of
      2.8 and 5.6 g/kg for 3 times, the incubation period of eyeball tremor induced by
      chloroform by dropping into the ear was prolonged by 14.4% and 13.0%, and the
      keeping time shortened by about 33.3% and 23.3% respectively. Brain basic
      arterial spasm induced by KCl or 5-HT in dog was relaxed obviously by XQC in
      vitro experiment. CONCLUSION: XQC has the effect of reducing blood pressure
      resisting dizziness, which is related to the diastole of brain blood vessel.

PMID- 12205870
TI  - [Research and development of wuzhuyu decoction].

PMID- 12205871
TI  - [Application of X-ray diffraction to the analysis of traditional Chinese
      medicine].
AB  - OBJECTIVE: To approach the application of powder Xray diffraction in analysis of
      traditional Chinese medicine(TCM). METHOD: Studying the references published in
      recent years and making a summary on the subject of application of Xray in the
      pharmaceutical analysis of TCM. RESULT: This method is effective in identifying
      and analyzing TCM. CONCLUSION: This technique may have broad prospects for
      pharmaceutical analysis.

PMID- 12205872
TI  - [Qualitative and quantitative studies on Chinese drug maidong].
AB  - OBJECTIVE: To explore a better approach to controlling the quality of Maidong.
      METHOD: The differences between Ophiopogon japonicus and the plants belonging to
      Liriope genus were identified by TLC. The total saponins in plants collected from
      different areas were determined by spectrophotometry, using HClO4 as the staining
      agent. RESULTS: The quantity of Maidong markedly varies with producing areas.
      CONCLUSION: This method is convenient and effective, and the MeOH extract of
      samples can be determined directly after reaction with HClO4 without preliminary
      treatment. The RSD was 0.75% (n = 5).

PMID- 12205873
TI  - [Studies on gel electrophoresis of soluble protein and two kinds of isodynamic
      enzyme in hongqu from different producing areas].
AB  - OBJECTIVE: To investigate the consanguinity between 12 strains of Monascus(MS 01
      12) separated and purified from different samples of Hongqu collected from 12
      areas in China and the variant strain of Monascus(MS 18) mutated from M.
      purpureus. METHOD: Gel electrophoresis of soluble protein, esterase and
      superoxide dismutase(SOD) was used to study the consanguinity between strains MS
      01-12 and the variant strain MS 18. RESULTS: The electrochromatophoreses of
      soluble protein, esterase and SOD in the 12 strains (MS 01-12) are identical, but
      in the variant strain MS 18 are remarkably different. The results are consistent
      with those of morphological studies. CONCLUSION: Strains MS 01-12 are the
      identical species M. purpureus, but strain MS 18 is different from strains of MS
      01-12, or a variant of M. purpureus.

PMID- 12205874
TI  - [Morphological studies on 18 species of gualoupi].
AB  - OBJECTIVE: To gain a clear idea of the drug Gualoupi and its adulterants. METHOD:
      Collecting data and spot investigating in 30 provinces, cities and autonomous
      regions in China. RESULT: Gualoupi used as drug in China consists of 15 species
      of Trichosanthes, 1 species of Momordica, 1 species of Citrullus and 1 species of
      Adenia(Passifloraceae). CONCLUSION: The main commodity is the rind of T.
      kirilowii or T. rosthornii, and the main adulterant is the rind of T. hupehensis.

PMID- 12205875
TI  - [Research on cause of distinction in antiendotoxic activation of radix isatidis
      from different cultivated populations].
AB  - OBJECTIVE: To research into the cause of distinction in antiendotoxic activation
      of Radix Isatidis from different cultivated populations. METHOD: 19 samples of
      Radix Isatidis were gathered. 12 portions of seeds were cultivated in the same
      field in Shanghai, and the selected and artificially bred autotetraploid seeds
      were planted in 5 different locations. All the samples were compared through
      antiendotoxic experiment. RESULTS: There are some marked distinction among the 19
      samples from different populations. The distinction of the 12 samples cultivated
      in the same field didn't disappear. The activation of autotetraploid from 5
      different locations didn't vary on the whole. CONCLUSION: Germplasm is the main
      factor to cause activation distinctions of Radix Isatidis, while environment is
      less important.

PMID- 12205876
TI  - [Studies on chemical constituents of seeds of Desmos chinensis Lour].
AB  - OBJECTIVE: To investigate the chemical constituents of Desmos chinensis. METHOD:
      Various column chromatographic techniques were employed for the isolation and
      purification of constituents from the ethanol extract. The structures were
      elucidated by spectral analysis. RESULT: Eleven compounds were isolated and
      identified as lawinal(1), desmosal(2), desmethoxymatteucinol(3), unonal(4),
      isounonal(5), desmosflavone(6), allantoic acid(7), succinic acid(8),
      daucosterol(9), beta-sitosterol(10) and stearic acid(11). The structures of
      compounds 1 and 2 were reconfirmed by NOEDS technique. CONCLUSION: Compound 2 is
      a new natural product and 7, 8 and 9 were found from this plant for the first
      time.

PMID- 12205877
TI  - [Studies on chemical constituents in the fruit of Canarium album Raeusch].
AB  - OBJECTIVE: To study the chemical constituents in the fruit of Canarium album.
      METHOD: Compounds were isolated by chromatography and elucidated on the basis of
      spectroscopic analysis. RESULT: The compounds obtained were determined as
      scoparone, scopoletin, (E)-3,3'-dihydroxy-4,4'-dimethoxystilbene and gallic acid.
      CONCLUSION: All the compounds, except gallic acid, were obtained from this plant
      for the first time.

PMID- 12205878
TI  - [Determination on chemical constituents of Curcuma L. produced in China].
AB  - OBJECTIVE: To provide some valuable information for the research on species
      systematization and quality standardization of Curcuma drugs. METHODS:
      Colorimetry, TLC-colorimetry and water vapour distillation were used to determine
      the contents of curcuminoids, curcumin and essential oils of 34 samples of
      Curcuma produced in China. RESULTS AND CONCLUSION: The contents of curcuminoids
      and curcumin are different upto an extent of over 100 times among the varieties
      of Curcuma, and those of essential oils to an extent of 6 times. But there is
      little difference in the samples of the same species from different producing
      areas. There is also an obvious correlativity between the contents of
      curcuminoids and essential oils in the varieties of curcuma.

PMID- 12205879
TI  - [Effects of Chinese patent medicine tongfugushen on adenine-induced chronic renal
      failure in rats].
AB  - OBJECTIVE: To observe the effects of Tongfugushen(TFGS) on adenine-induced
      chronic renal failure in rats. METHODS: The model of chronic renal failure was
      made by feeding rats with food containing 0.5% adenine. Two weeks later, along
      with the above food, the treated group was administered the Chinese patent
      medicine TFGS, and the control group was given NS. Blood tests including urea
      nitrogen(BUN), serum creatinine(Scr), red blood cell(RBC), hemoglobin (Hb),
      hematocrit(HCT) and renal pathological tests were performed at the end of the
      fourth week. RESULT: In the TFGS treated group, the mean levels of BUN and Scr
      were lower and the mean values of RBC, Hb and HCT were higher than those in the
      control group, and the deposited crystals of adenine metabolite and the
      proliferation of fibroid tissue in kidney were decreased. CONCLUSION: TFGS is
      helpful in improving the symptoms of chronic renal failure in rats.

PMID- 12205880
TI  - [Studies on Chinese drugs zhiqiao and zhishi origin investigation and merchandise
      identification].
AB  - OBJECTIVE: To sort out the main original plants of Chinese drugs Zhiqiao and
      Zhishi. METHOD: Investigating the medicinal plant resources in the growing area
      and conducting morphological identification of more than 40 pieces of these two
      commercial drugs. RESULT: A taxonomic table, a distribution table and a
      commercial drug identification table are given. CONVLUSION: The Chinese medicinal
      plants Zhiqiao and Zhishi originated from Citrus aurantium and its varieties C.
      aurantium "Xiucheng", C. aurantium "Xiangcheng" and Poncirus trifoliata x C.
      aurantium, some other plants from Citrus genus and Poncirus trifoliata are taken
      as the origin of Zhiqiao and Zhishi only in a few areas.

PMID- 12205881
TI  - [Studies on pharmacognostic identification and quality control standards for
      hongqu].
AB  - OBJECTIVE: To develop effective methods for quality control of the traditional
      Chinese drug Hongqu. METHOD: TLC and microscopic identification were performed.
      HPLC was used to determine the content of lovastatin. RESULT: A lot of hyphae and
      spores in Hongqu were observed under microscope. The spot of lovastatin was found
      on the TLC chromatogram. The standard curve of lovastatin by HPLC was linera in
      the range of 5 micrograms/ml-100 micrograms/ml. The average recovery of
      lovastatin was 96.4%, RSD 3.68%, n = 5. CONCLUSION: The methods are simple,
      sensitive and accurate. These studies provide the scientific basis for quality
      evaluation and quality control of Hongqu.

PMID- 12205882
TI  - [Ultrastructural changes after space flight in Platycodon grandiflorum (Jacq.)
      DC].
AB  - OBJECTIVE: To substantiate the effect of space conditions on medicinal plants.
      METHOD: The seeds of platycodon grandiflorumg were set up in retrievable
      satellites. After returning to earth, the ultrastructural changes of leaves were
      studied. RESULT: Under light microscope, the leaf tissue structure of the flight
      group and the earth controlled group were alike and under electron microscope,
      some differences could be found in the nucleus and choloroplasts between the two
      groups. CONCLUSION: Space environment has some effect on Platycodon grandiflorum,
      and the effect needs to be further explored.

PMID- 12205883
TI  - [A study on maillard reaction and its products during processing of red ginseng].
AB  - OBJECTIVE: To isolate and identify maltol and maltol-3-O-beta-D-glucoside and
      argininyl-fructosyl-glucoside in red ginseng, and prove that they are products of
      processing through comparative analysis and artificial synthesis of different
      products of ginseng. METHOD: Column chromatography, spectral analysis, TLC
      scanning quantification, amino acid analysis and artificial synthesis on
      simulated conditions. RESULT: Maltol and its glycoside are peculiar components in
      red ginseng, and the content of argininyl-fructosyl-glucoside in red ginseng the
      product of processing is three times higher than that of white ginseng.
      CONCLUSION: Maillard reaction exists in the processing of red ginseng, thus
      proper control of this reaction helps improve the quality red ginseng.

PMID- 12205884
TI  - [Chemical constituents of Pistia stratiotes L].
AB  - OBJECTIVE: To investigate the chemical constituents of Pistia stratiotes, a kind
      of duckweed. METHOD: Compounds were separated by chromatography on sillica gel,
      and their structures were identified by spectral analysis and chemical evidence.
      RESULT: Four compounds were obtained and identified as stigmasta-4,22-dien-3-one,
      stigmasterol, stigmasteryl stearate and palmitic acid. CONCLUSION: All the four
      compounds were isolated from this plant for the first time.

PMID- 12205885
TI  - [Preliminary study on chemical changes in the decocting process of radix et
      rhizoma Rhei].
AB  - OBJECTIVE: To understand the chemical changes in the decocting process of Radix
      et Rhizoma Rhei. METHOD: Comparing the contents of many kinds of anthraquinones
      in the crude drug, decoction and drug sediments of Radix et Rhizoma Rhei by HPLC.
      RESULT: The contents of combined and free anthraquinones changed after the crude
      drug was decocted. CONCLUSION: These changes may be related to the hydrolysis of
      combined anthraquinones, the decomposition of free anthraquinones, and the inter
      transition among anthraquinones.

PMID- 12205886
TI  - [Studies on chemical constituents and pharmacological effects of the stem of
      Cynomorium songaricum Rupr].
AB  - OBJECTIVE: In order to exploit the medicinal resources and provide a scientific
      evidence for the clinical use and quality of Cynomorium songaricum control, the
      chemical constituents and pharmacological effects of the stem of the plant were
      studied preliminarily. METHOD: The chemical constituents were studied by spectral
      analysis and chemical method. The pharmacological effects were studied by an
      experiment on the defecation and deficiency of kidney function. RESULT AND
      CONCLUSION: Seven compounds were isolated from the stem of C. songaricum and
      identified as beta-sitosterol(I), palmitic acid (II), ursloic acid (III),
      daucosterol (IV), (-)-catechin (VI), naringenin-4'-O-pyranogluoside (VII) and
      succinicyacid (XII). Compounds VI and XII were isolated from this species for the
      first time. The pharmacological results show that the different extracts
      facilitate catharsis and replenish the deficiency of kidney yang.

PMID- 12205887
TI  - [Isolation and identification of saxifragin from Glycyrrhiza uralensis Fisch].
AB  - OBJECTIVE: To extract flavonoid constituents from Glycyrrhiza uralensis. METHOD:
      30% EtOH extraction and column chromatographic isolation. RESULT: A flavonoid
      compound was isolated. CONCLUSION: Obtained from G. uralensis for the first time,
      the flavonoid compound was identified as saxifragin through spectral, physical
      and chemical analyses.

PMID- 12205888
TI  - [Studies on chemical constituents of Forsythia suspensa (Thunb) Vahl].
AB  - OBJECTIVE: To study the chemical constituents of Forsythia suspensa. METHOD:
      Basedon silicacolumn chromatography, of which six compounds were obtained from
      the alcohol extract of F. suspensa, three identified by physicochemical and
      spectroscopic analyses. RESULT: The three compounds were identified as stearic
      acid, palmitic acid and beta-sitosterol. CONCLUSION: The three compounds were
      separated from F. suspensa fruits for the first time.

PMID- 12205889
TI  - [Pharmacological comparison between volatile oil and water extract].
AB  - OBJECTIVE: To compare the pharmacological differences between volatile oil and
      water extract in eight aromatic drugs for resolving dampness. METHOD: Volatile
      oil and water extract of eight commonly used aromatic drugs for resolving
      dampness were ig administered to rats respectively, and the effects of volatile
      oil and water extract on the secretion of gastric juice, volume of gastric mucous
      blood flow and activity of SOD in gastric mucous membrane were studied. RESULT:
      It was shown that the effects of aromatic volatile oil in eight drugs on the
      indexes mentioned above were generally equal or similar to those of water
      extract, and it was obvious that the volatile oil in some high oil content drugs
      such as Amonum cardamomum L(Baidoukou), Alpinia katsumadai Hagata (Caodoukou),
      Amomum villosum Lour (Saren), and Amomum tsao-ko Crevost et Lem (Caogou) had
      better effects on the secretion of gastric juice and volume of gastric mucous
      blood flow that those of water extract. CONCLUSION: It has been pharmacologically
      proved that in using aromatic drugs for resolving dampness, the loss of aromatic
      (volatile) components should be avoided.

PMID- 12205890
TI  - [Experimental research of Ephedra sinica's influence on lipid metabolism of
      lipocyte].
AB  - OBJECTIVE: To study the influence of Ephedra sinica on the lipid metabolism of
      lipocyte. METHOD: The rat's epididymal lipocytes were used to observe the effect
      of Ephedra sinica in lipogenesis from 14C-glucose and lipolysis promoted by
      norepinephrine (NE). RESULT: Ephedra sinica can promote lipogenesis from glucose,
      which is related with the pH value of matrix solution; and it also can inhibit
      the lipolysis promoted by NE. CONCLUSION: Ephedra sinica can promote the
      lipogenesis of lipocyte that is not induced by ephedrine, the mechanism being
      similar to that of insulin.

PMID- 12205891
TI  - [Effect of puerarin on coronary collateral circulation in dogs with experimental
      acute myocardial infarction].
AB  - OBJECTIVE: To evaluate the effect and mechanism of puerarin on coronary
      collateral circulation in dogs with experimental acute myocardial infarction.
      METHOD: Twelve dogs were randomly divided into puerarin (Gegen su, G) group and
      control(C) group, the acute myocardial infarction model was built in all dogs.
      Puerarin or saline was administered for 21 days. Coronary angiography was
      performed before and after ligating coronary artery. The capillaries and
      distribution vessel density in tissue sections of myocardium were assessed.
      RESULT: Angiography on hour 2 and day 22 after ligating coronary artery revealed
      significant augmentation of collateral vessels in G group versus controls.
      Capillaries and distribution vessel density in ischemic and infarctive zone on
      day 22 revealed statistically significant augmentation in G group versus controls
      (P < 0.05 and P < 0.01). CONCLUSION: Puerarin might improve the opening and
      forming of coronary collateral circulation to ischemic myocardium in dogs and
      protect ischemic myocardium.

PMID- 12205892
TI  - [Determination of alkaloids in Coptis-Cinnamomum compatibility by capillary
      electrophoresis].
AB  - OBJECTIVE: To establish a HPCE method to determine the contents of alkalods in
      Rhizoma Coptidis. METHOD: HPCE. RESULT: The constituents thus determined have
      good linearity and separation. The average recovery of coptisine, berberine,
      palmatine and jatrorrhizine was 98.28%, 98.38%, 97.78% and 98.89% respectively
      and RSD 0.86%, 1.12%, 1.06% and 1.11% respectively. CONCLUSION: The method is
      convenient, rapid, accurate and practicable. The compatibility reduces the
      contents of alkaloids in Rhizoma Coptidis in different degrees.

PMID- 12205893
TI  - [Advance in the research on triterpenoids of tribe Cimicifugeae].

PMID- 12205894
TI  - [A study on producing areas of Chinese flos Dendranthematis].
AB  - OBJECTIVE: To probe into the cultural environment and changes of producing areas
      of different species of Chinese Flos Dendranthematis. METHOD: On-the-spot
      investigation and literature study. RESULTS: A clearer idea has been gained on
      the geographical distribution, growing environment and changes of producing areas
      of Gongju, Hangju, Chuju, Boju, Huaiju and Jiju. CONCLUSION: Different
      environments fit for the growth of different species of Flos Dendranthematis. The
      present study provides some valuable information on the cultivation and
      development of Chinese Flos Dendranthematis.

PMID- 12205895
TI  - [Studies on tannin and hydrolysate in three species of Chinese Caesalpinia
      plants].
AB  - OBJECTIVE: To get Chinese Caesalpinia plants that can replace the imported Tara
      to produce tannin and gallic acid. METHOD: Extract tannin with water, condense
      and hydrolyze the extracts with alkali, the hydrolysates were identified.
      Furthermore, an enlarged scale experiment was conducted. RESULT: Tannin contents
      of the plants were 32.2%, 46.6% and 58.5% respectively, the converted ratios of
      raw material to hydrolysate were 154:1, 11.8:1, 3.09-2.79:1 respectively.
      CONCLUSION: We got the Tara-replacing plants in Chinese Caesalpinia plants for
      the first time.

PMID- 12205896
TI  - [Identification of medicinal and edible tender shoots of Aralia in China].
AB  - OBJECTIVE: To Study the identification of medicinal and edible tender shoots of
      Aralia in China. METHODS: Morphological identification and differential thermal
      analysis(DTA). RESULTS: Important morphological and DTA features for
      identification were found. CONCLUSION: It is difficult to identify these tender
      shoots merely on morphological characteristics, but the combination of
      morphological features with distinctive aspects of DTA curve helps distinguish
      these species and give an identification index.

PMID- 12205897
TI  - [Effects of cultivating measures on rhizome yield and some main active
      constituents of Curcuma longa L].
AB  - OBJECTIVE: To substantiate the effects of cultivating measures on the rhizome
      yield and main active constituents of Curcuma longa. METHOD: Randomized block
      design was applied to the study of the sowing time and plant density, and
      orthogonal experiment L9 (3(4)) was conducted to determine the quantity of
      fertilizer. RESULT: The effects of cultivating measures on the rhizome yield and
      some main active constituents of Curcuma longa were noticeable. The rhizome yield
      went up, and the contents of curcuminoids and essential oils went down with the
      increase of fertilizer application. CONCLUSION: The main cultivating measures for
      high-yield and good-quality of rhizome: rational sowing time-late March, plant
      population-12 checkrows per m2, 1 mother rhizome per checkrow. The suitable
      fertilizer requirements have also been formulated.

PMID- 12205898
TI  - [Comparison of constituents extracted from prepared Licorice by semi-bionic
      extraction with those by water extraction].
AB  - OBJECTIVE: To study the granulation of prepared licorice. METHOD: Semi-bionic
      extraction(SBE) and water extraction(WE) were used in the extraction of prepared
      licorice, and then compared with glycyrrhetinic acid, total flavone and extract
      with which were taken as the indexes. RESULT: SBE is superior to WE. CONCLUSION:
      It is better to use SBE in the preparation of oral licorice granules.

PMID- 12205899
TI  - [Anthraquinones in Eremurus chinensis Fedtsch].
AB  - OBJECTIVE: To investigate the chemical constituents in herbs of Eremurus
      chinensis METHOD: The chemical constituents were extracted with solvents and
      separated by column chromatography. RESULTS: The structures were identified by
      spectral analysis as chrysophanol, 10-(chrysophanol-7'-yl)-10-hydroxychrysophanol
      9-anthrone and phthalic acid dibutyl ester. CONCLUSION: All the three compounds
      were separated from E. chinensis for the first time.

PMID- 12205900
TI  - [Separation and identification of thellungianin G from the root of Pimpinella
      thellungiana Wolff].
AB  - OBJECTIVE: To study the effective components in the root of Pimpinella
      thellungiana METHOD: Column chromatography with silica gel and ODS was employed
      for the isolation and purification of ingredients. Their structures were
      elucidated by spectral analysis. RESULT: Three compounds were obtained and
      identified as 2-(1',2'-epoxy)-4-methoxy pheryl-2-methyl-butyrate(I),4-(1'
      propenyl) phenol(II) and 2-methyl butyric acid(III). CONCLUSION: Compound I is a
      new compound and named thellungianin G. Compounds II and III were separated from
      P. Thellungiana for the first time.

PMID- 12205901
TI  - [Determination of columbianetin, columbianetin acetate and osthol in Angelica
      pubescens Maxim. f. biserrata Shan et Yuan by HPLC].
AB  - OBJECTIVE: To develop a method for the determination of columbianetin,
      columbianetin acetate and osthol in Angelica pubescens f. biserrata METHOD: HPLC
      method, ODS column (6.0 mm x 150 mm) with a mobile phase of methanol-acetonitrile
      0.025 mol.L-1 phosphoric acid (32:20:48), and wave length detection at 320 nm.
      RESULT AND CONCLUSION: The method can be used for the quality control of raw
      medicinal materials.

PMID- 12205902
TI  - [Determination of sarsasapogenin in Anemarrhena asphodeloides Bunge by GC].
AB  - OBJECTIVE: To determine sarsasapogenin in Anemarrhena asphodeloides. METHOD:
      Chloromethane extract (1 microliter) with cholesterol as internal standard was
      analyzed on HP-1 column, operated at 270 degrees C with N2 as carrier gas and
      FID. RESULT: The method was linear within the range of 0.245-2.94
      micrograms.microliter-1, with a correlation coefficient of 0.9996. The average
      recovery was 95.52% +/- 1.77%, CONCLUSION: The method is reproducible, rapid and
      sensitive.

PMID- 12205903
TI  - [Synergistic interaction between Ys-96, a bisbenzylisoquinoline compound derived
      from Stephania tetrandra, and adriamycin or vincristine against human cancer cell
      lines in vitro].
AB  - OBJECTIVE: To study in vitro the anticancer interaction between Ys-96, a
      bisbenzylisoquinoline compound derived from Stephania tetrandra, and adriamycin
      or vincristine against human cancer cell lines. METHOD: Using human breast cancer
      cell MCF-7 and its adriamycin-resistant cell line MCF-7/Adr, and human
      nasopharyngeal cancer cell KB and its vincristine-resistant cell line KBv200 in
      an in vitro system, anticancer interaction between Ys-96 and adriamycin or
      vincristine was evaluated with a method reported by Berenbaum. RESULT: The SFIC
      values (sum of fractional inhibitory concentration) of the combinations with 3
      different ratios between Ys-96 and adriamycin or vincristine were markedly less
      than 1.0, and the shapes of all the isobologram curves were concave. CONCLUSION:
      The synergistic interaction between Ys-96 and adriamycin or vincristine against
      the above human cancer cell lines was positively observed in vitro.

PMID- 12205904
TI  - [Skeletal effect of xianzhen gubao on preventing prednisone-induced osteoporosis
      in male rats].
AB  - OBJECTIVE: To study the effect of Chinese medicine Xianzhengubao (XZGB) capsules
      of compound prescription on corticosteroid-induced osteoporosis in rats. METHOD:
      3-month-old SD male rats were randomly divided into basal control and aging
      control, prednisone (4.5 mg.kg-1, ig, twice a week) and XZGB capsules were used
      in three different doses (0.2, 0.4, 0.8 g.kg-1.d-1 ig)6 times a week. All the
      rats were killed. On the 90th day afteradministration. The proximal tibiae were
      processed in undecalcified sections at a thickness of 4-10 microns for
      histomorphometric analysis. RESULT: Compared with the aging controls
      corticosteroid reduced markedly the trabecular bone mass due to increase of bone
      resorption and decrease of bone formation (%Tb. Ar 52.9%). Treatment with XZGB
      capsules in high doses increased significantly the trabecular area as compared
      with the hormone control(% Tb. Ar + 91.2%). The protective mechanism of XZGB
      capsules mainly consists in suppressing bone resorption and mildly increasing
      bone formation in rats. CONCLUSION: Xianzhen gubao capsules have an effect on
      preventing bone loss in rats induced by corticosteroid, and higher doses produce
      greater effect.

PMID- 12205905
TI  - [Expression and distribution of bFGF mRNA in lung tissue of rat with chronic
      pulmonary hypertension].
AB  - To evaluate the role of basic fibroblast growth factor (bFGF) in the development
      of hypoxic pulmonary hypertension, 30 wistarmale rats were divided into hypoxic
      group and control group. Rat models with chronic hypoxia induced pulmonary
      hypertension were established. The pulmonary hemodynamics was measured and the
      concentration of bFGF in rat lung tissue was determined quantitatively by enzyme
      linked immunosorbent assay (ELISA). Expression and distribution of bFGF messenger
      ribonucleic acid (mRNA) in rat lung was observed by in situ hybridization using
      digoxigenin-labeled oligonucleotide probe. The result showed the mean pulmonary
      artery pressure and the concentration of bFGF in rat lung tissue were 3.96 +/-
      0.47 kPa, 18.06 +/- 2.97 pg/ml in rats exposed to hypoxia for 3 weeks,
      respectively; both were significantly higher than those in control group (P <
      0.01, P < 0.001 respectively); expression of bFGF mRNA in the wall of pulmonary
      arterioles in rats exposed to hypoxia was stronger than that of control group.
      bFGF mRNA increased obviously in endothial cells, smooth muscle and advential
      tissue of pulmonary arterioles. These suggest that bFGF takes part in
      reconstruction of pulmonary arterioles wall in chronic hypoxic pulmonary
      hypertension, and the main mechanism of bFGF in modulating the structural
      remodeling of pulmonary arterioles may be autocrine and paracrine.

PMID- 12205906
TI  - [Effect of po li gan capsule on immunofunction in mice].
AB  - This study aimed at the immune response of mice to Po Li Gan Capsule (PLGC). The
      effects of PLGC on phagocytosis of phagocyte, on serum hemolysin, and on IL-1, IL
      2 in mice were investigated. The results showed that the coefficient and index of
      phagocytosis obviously increased in the experiment group, compared with that in
      the control group (P < 0.01); the serum hemolysin in the experiment group
      increased too (P < 0.01). The results also showed that PLGC could restore the
      capacity of macrophage for secreting IL-1 that had been inhibited by
      cyclophosphamide and PLGC could enhance the release of IL-2 from spleen cell in
      the experiment group (P < 0.05-0.01). These suggest that PLGC enhances both
      cellular and humoral immunity function in mice.

PMID- 12205907
TI  - [Anaerobic bacterial analysis of 436 specimens of clinical infection].
AB  - This study was aimed at the relationship between anaerobes and clinical
      infection. Aerobic and anaerobic bacterial culture was performed for 436
      specimens of clinical infection. The incidence of anaerobic bacteria isolates and
      predominant species were analyzed. The results showed that the incidence of
      anaerobic isolates was 88.3% (385/436), the main predeminoue species were Gram
      negative nonsporeforming anaerobic rods (Bacteroids, Prevotella and
      Porphyromonas) and peptostreptococcus. The endogenous infection, caused by
      anaerobic microflora of human body as the main pathogens, and the mixed bacterial
      infection are the most common feature of human clinical anaerobic infections.

PMID- 12205908
TI  - [The standardized techniques for preparing samples used in pathologic diagnostic
      transmission electron microscopy].
AB  - Transmission electron microscopy (TEM) has been used widespreadly in the field of
      diagnostic pathology. Based on the practical domestic condition and aimed at
      fully satisfying the needs of the pathologic diagnostic TEM, a set of
      standardized techniques were established for preparing different kinds of
      samples. The techniques included the preparation and storage of fixatives and
      embedding media, the requirement of sampling, the 5 h and 24 h embedding
      procedures for fresh specimens, the embedding procedure for suspension specimens
      and specimens collected from fine needle aspiration biopsy, as well as the
      procedures for preparing samples taken from paraffin embedded blocks or paraffin
      sections. In practical use, we found that the advantage of these techniques was
      that the ultrastructures of the tissues and cells were well preserved and they
      perfectly met the needs for diagnosis of tumors, kidney diseases, et al. The main
      points of the standardized techniques have been discussed in detail in this
      paper.

PMID- 12205909
TI  - [Isolation of isoforms of apolipoprotein CIII from human serum by
      chromatofocusing].
AB  - This study aimed to isolate isoforms of apolipoprotein (apo) C III from human
      serum. 24-hour fasting serum from normal and hyperlipidemic subjects was pooled
      and subjected to ultracentrifugation at plasma density for 20 hours. Very low
      density lipoprotein (VLDL) was collected at density of d < 1.006 g/ml, and it was
      delipidated by ethanol and ether. The delipidated apo-VLDL was dissolved in a
      solution containing 7.2 mol/L urea and 20 mmol/L dithiothreitol. The insoluble
      apo B was removed by centrifugation. The soluble apo-VLDL was applied to PBE94
      column, and eluted with elution buffer containing polybuffer 74 and 8 mol/L urea
      (1:8, pH4.0). After pooled, the eluted peaks of apolipoproteins were applied to
      column chromatography of hydroxylapatite to remove the polybuffer. The purified
      isoforms of apoC III and the purified apo C I, C II and E, were characterized by
      isoelectrofocusing and west blot. The results showed that the purified apoC III1,
      C III2, and C II were pure.

PMID- 12205910
TI  - [Plasma HDL subfractions in endogenous hypertriglyceridemia].
AB  - Our previous studies indicated that while the plasma triglycerides (TG) levels
      were significantly increased, HDL-C and apo A I levels were significantly
      decreased and abnormal HDL compositions were found in hypertriglyceridemic (HTG)
      patients. Whether the particle sizes of plasma HDL in HTG undergo a change has
      not yet been reported. This study was designed to observe the changes of plasma
      HDL subfractions in HTG patients. The plasma TG, total cholesterol (TC), HDL-C,
      apo A I, A II, B100, C II, C III, and E, HDL compositions and HDL subfractions-
      HDL2a, HDL2b, HDL3a, HDL3b and HDL3c were measured in 25 HTG patients (plasma TG
      > 2.26 mmol/L, TC < 6.72 mol/L) and 25 age-sex matched healthy subjects (plasma
      TG < 1.69 mmol/L, TC < 5.17 mmol/L). Plasma HDL was isolated by one step density
      gradient ultracentrifugation. Plasma and HDL TC, TC were determined by enzymatic
      methods; apo A I, A II, B100, C II, C III and E were measured by RID kits
      developed by ourselves. HDL subfractions were analyzed by a gradient gel
      electrophoresis method (GGE). The variation coefficients in one gel were 2.3% to
      8.3% and the variation coefficients among gels were 3.5% to 9.3%. The results
      indicated that in the HTG group, the fasting plasma TG, apo B100, C II, C III and
      E levels were significantly higher (P < 0.001) and HDL-C, apo A I levels were
      lower (P < 0.05) as compared with those in the control group. TC in HDL in the
      HTG group were significantly increased (P < 0.05), while TG, apo A I, C II, C III
      and E were significantly decreased (P < 0.05, P < 0.01). Among HDL subfractions
      in the HTG group, HDL2b was significantly decreased (P < 0.02); HDL2a and HDL3a
      were increased (P < 0.05, P < 0.02). With the increase of plasma TG levels in the
      HTG group, the HDL particle sized tended to become smaller. According to the
      results, it is suggested that the changes of plasma HDL subfractions in HTG are
      related to the changes of the apolipoprotein compositions of HDL, which lead to
      the increase of HDL catabolism, therefore the plasma HDL2b content decreases and
      HDL2a, HDL3a contents increase.

PMID- 12205911
TI  - [An experimental study on the biological basis of cortex-to-cortex bone healing
      after oblique ramus osteotomy].
AB  - This study was designed to elucidate biological basis of cortex-to-cortex bone
      healing after oblique ramus osteotomy. 12 rhesus monkeys were subjected to
      oblique ramus osteotomy bilaterally, and the operated sites were examined by
      microvascular irrigation section and histology techniques. The results showed
      that, besides the blood supply from the attachment of lateral pterygoid muscles
      and capsule of temporomandibular joint to the medial segments, the blood supply
      from the attachment of medial pterygoid muscles also played an important role.
      Cortex-to-cortex bone healing was achieved by the formation of a large volume of
      scab surrounding the operated sites. It is concluded that oblique ramus osteotomy
      has its good biological basis both in blood supply and cortex-to-cortex bone
      healing process.

PMID- 12205912
TI  - [Comparative study of the effect on stress distribution of porcelain laminate
      complex with different elastic moduli].
AB  - Porcelain laminate has been a kind of popular treatment modality for its
      aesthetics and less tooth reduction. The models of 3-D FEA of left upper
      permanent central incisor were designed by microtomy. Comparative studies of
      stress distribution were carried out to reveal the stress of three designs of
      tooth preparation with two kinds of occlusions. The results showed that under
      loads imitating of central occlusion, the stress level increased a little with
      the rising of elastic modulus of the porcelain material, while the stress values
      of type II veneer seemed the highest under loads imitating of protruding
      occlusion. For the designing of laminate, it implies that porcelain material with
      low elastic modulus should be used in case of type II veneers.

PMID- 12205913
TI  - [The behaviour of rat mandibular condylar cartilage in cell culture].
AB  - This study aimed to identify the behaviour of mandibular condylar chondrocytes in
      vitro. Cells were harvested from the mandibular condyles of 3 week-old S. D.
      rats. Cell structure, morphology and characteristics were assessed by phase
      contrast microscopy, scanning electron microscopy, enzymohistochemistry and
      immunohistochemistry. The cultured condylar chondrocytes, stellated or spindle
      shaped, could grow in several layers and form many cell colonies. They could
      secret proteoglycans, alkaline phosphatase, type II collagen, et al. The methods
      of isolation, culture and identification of condylar chondrocytes were presented
      and discussed, which can be adopted in probing further into the cellular
      mechanism of functional orthopedics.

PMID- 12205914
TI  - [A study on porins of Escherichia coli HX88108].
AB  - To investigate the relationship between porins deficiency and the resistance of
      Escherichia coli HX88108. The porins of Escherichia coli HX88108 were studied by
      SDS-PAGE and were compared with the porins of standard strains. The result showed
      that E. coli HX88108 did not lose OmpF and OmpC, and the molecular weights of
      these two porins were 38 kd and 37 kd respectively. There is no relationship
      between the resistance of Escherichia coli HX88108 and porins deficiency.

PMID- 12205915
TI  - [Purification and identification of pili of Vibrio cholera O139].
AB  - To provide the base of manufacturing V. cholera O139 subunit vaccine,
      purification and identification methods of V. cholera O139 Toxin-coregulated pili
      (TCP) were studied. The results showed the optimal expressing condition of TCP
      was in AKI or CFA medium, at 30 C for 24-36 h with stationary cultivation. The
      molecular weight of the TCP subunit protein measured by sodium dodecyl sulfate
      poly acrylamide gel electrophoresis was about 20.5 kd. By using mouse anti-TCP
      monoclone antibody and sheep anti-mouse IgG-HRP antibody, the TCP was confirmed
      by dot blot immunoassay. Rabbit immune serum of TCP purified from O139 strain
      agglutinated both O139 biotype and El Tor biotype Vibrio cholera strains. These
      indicate that TCP may be an effective and protective antigen to conduct the
      preparation of V. cholera vaccine.

PMID- 12205916
TI  - [Preparation of oral microspheres carrying V. cholera vaccine and its target's
      distribution].
AB  - To prepare oral biodegradable microspheres carrying V. cholera vaccine, the major
      outer membrane protein (OMP, MW = 41 kd) as a common antigen of cholera Vibriae
      was obtained from the classical strain Inaba 569 B, and the OMP was encapsulated
      in the biodegradable delivery system comprising Poly (DL-Lactide)-Co
      Poly(ethylene glycol)microspheres. The average size of the microspheres was less
      than 5 microns, the amount of OMP encapsulated in microspheres was 15.3%. It was
      found that microspheres were taken up in Peyer's patches and then distributed in
      spleen, liver and mesenteric lymph nodes after oral administration.

PMID- 12205917
TI  - [An investigation of immunoprotecting mechanism of macroencapsulated pancreatic
      islet xenograft].
AB  - Macroencapsulated islet xenografts in agarose are able to prevent rejection. This
      study was conducted to shed light on the immunoprotecting mechanism of
      macroencapsulated islet xenografts in agarose. There were four groups (n = 5 in
      each group): (1) macroencapsulated islet xenografts in agarose; (2)
      nonencapsulated islet xenografts; (3) agarose macroeencapsule without islet; (4)
      syngenic pancreatic islets. Mixed lymphocyte islet culture (MLIC) was used in the
      experiment. The results showed that stimulating index (SI) of MLIC and IL-2 level
      in the macroencapsulated islet xenografts in agarose group were similar to those
      of syngenic pancreatic islets group. The SI and IL-2 levels of nonencapsulated
      islet xenograft group were significant higher than those in macroencapsulated
      islet xenografts in agarose group and syngenic pancreatic islets group. These
      indicate that macroencapsulation is capable of reducing the immunogenicity of
      islet xenograft, and it is presumable that macroencapsulated islet xenografts in
      agarose be not recognized by the recipient's immune system because of being
      separated by the selectively permeable membrane made with agarose.

PMID- 12205918
TI  - [The synthesis of multifunctional groups and multibranched compounds: IX.
      Synthesis of several branched building block].
AB  - The branched building plays a pivotal part in the study of Dendrimers. In order
      to synthesized Dendrimers more effectively, we designed and synthesized four new
      branched building blocks via 2-4 steps starting from diethyl malonate and
      pentaerythritol. Their structures were confirmed by IR and 1HNMR etc. They
      compare favourably with previous branched building blocks as regards to steric
      hindrance and branched effect.

PMID- 12205919
TI  - [Investigation of inhibitory effect of ramipril on apoptosis in spontaneously
      hypertensive rats].
AB  - To explore the effect of angiotensin converting enzyme (ACE) inhibitor on
      apoptosis in spontaneously hypertensive rats(SHR), and normotensive control rats
      (WKY) at different ages were used. Ramipril (1 mg.kg-1.d-1) was administered
      orally to male SHR from 3 or 5 weeks to 10 weeks of age. Male and age-matched
      untreated SHR and WKY were used as controls. Experiments determined. Apoptosis in
      cardiomyocytes of SHR was quantified by a maximal labeling (Lmax) method and the
      characteristic features of apoptosis were identified by electron microscopy (EM),
      in situ labeling of DNA strand breaks with terminal deoxynucleotidyl transferase
      mediated dUTP end labeling (TUNEL) and autoradiographic analysis of DNA
      fragments. The results of the quantitative method showed an age-dependent
      increase in apoptosis in the cardiac tissues of SHR. A significant increase in
      DNA breaks occurred as early as age 4 weeks and continued to increase up to a
      plateau at age 16 weeks in the cardiac tissue of SHR, whereas there was no
      significant change in apoptosis in WKY up to 64 weeks. Moreover, after the
      treatment of SHR with ramipril, an inhibitor of ACE, the DNA fragmentation, like
      BP and HW/BW, was reduced significantly (70.7%) as compared with that of
      untreated SHR(P < 0.01); and similar to that of the WKY (P > 0.1), the DNA ladder
      disappeared, which was very obvious in the untreated SHR. These studies
      demonstrate that ramipril can prevent the development of hypertension and
      myocardial hypertrophy and can inhibit the increase in the apoptosis of SHR
      cardiac myocytes, suggesting that apoptosis may be involved in the pathogenesis
      of genetic hypertension.

PMID- 12205920
TI  - [Intracerebral distribution of albumin after closed brain traumas].
AB  - Twenty cases of closed brain traumas were investigated immunohistochemically to
      detect intracerebral distribution of albumin. The brain contusions' areas were
      heavily stained in all cases, even in those of only 15 minutes' survival. Some
      neurons, nerve fibers, astrocytes and gitter cells of the softening area both
      nearby the contusion areas and far from the contusion areas, including thalamus,
      midbrain, pons and medulla, were also heavily stained in all cases. The marked
      immunoreactivity to albumin also took place in extravascular spaces, endothelial
      cells and membrane of red blood cells. The results suggested that
      immunohistochemical staining of albumin should be a sign of early brain trauma,
      inclusive of brainstem trauma. It is especially useful in the identification of
      brain traumas without bleeding.

PMID- 12205921
TI  - [Study on cross-sections at the plane of the aortic arch and its adjacent
      structures].
AB  - The purpose of this study was to describe and explain the normal appearances of
      aortic arch and its adjacent structures on the transaxial sections and to provide
      anatomical data for the diagnosis of CT and MR images. Dissections were performed
      on 1.2 cm interval cross-sections of the thorax of 30 embalmed cadavers. The
      results showed 20.00 +/- 7.30% of the aortic arch and arch of the azygos vein at
      the same plane and 40.00 +/- 8.94% of the arch of the azygos vein at the level of
      concavity of the aortic arch. 80.00 +/- 7.30% of the top of the superior aortic
      recess extended to the level of the aortic arch from which the branchiocephalic
      trunk arises. At the level of the aortic arch, 100% of the lymph nodes of
      superior vena cava were located among the aortic arch, superior vena cava and
      trachea. At the level of azygos vein, 100% of the lymph nodes of azygos vein and
      the superior aortic recess were located among the superior vena cava, arch of
      azygos vein, trachea and concavity of aortic arch. These data suggest that aortic
      arch and arch of azygos vein are the key structures to identify the superior
      aortic recess and lymph nodes. They are essential for understanding the related
      pathologic changes depicted on CT and MR images.

PMID- 12205922
TI  - [PCR amplification and cloning of the specific region of the gene encoding 83kd
      antigen from Borrelia burgdorferi].
AB  - According to the published gene sequence coding the 83 kd antigen from B31 strain
      of Borrelia Burgdorferi, we selected the region from 1419 bp to 1896 bp as the
      target sequence to design a pair of oligonucleotide primers, obtained the gene
      fragment by using PCR, and recombinant expression vector pBX1 by cloning the gene
      fragment into plasmid vector pBK-CMV. The recombinant plasmid can be made into
      nucleic acid probe for the classification of Borrelia burgdorferi. The gene
      fragment product expressed by pBX1 can be used as antigen in the serological
      diagnosis of Lyme disease.

PMID- 12205923
TI  - [Comparative study of ventilatory functions of smokers with MTTp and F-V curve
      configuration].
AB  - To assess the clinical significance of partial mean transit time(MTTp) and F-V
      curve configuration for testing small airway functions in smokers, routine
      ventilatory functions, MTTp and F-V curve configuration were studied in 116
      passive and active light, heavy smokers. Routine ventilatory functions and F-V
      curve configuration were determined with routine methods. MTTp were calculated
      with "convenient calculation". The results showed that the distribution of convex
      type of F-V curve rose with the degree of smoking. The decrease of V50, V25 and
      prologation of MTT45%-55%, MTT70%-80% in convex type were just correspondent with
      heavy smokers. The range of prolongation of MTT45%-55% and MTT70%-80% was 110%
      120% of predicted value both in heavy smokers and convex type. These showed there
      were light disturbances in small airways. Therefore, the convex type, the
      prolongation of MTT45%-55% and MTT70%-80%, and the decrease of V50 and V25 should
      all be used as sensitive indices for testing small airway functions. The value of
      MTTp calculated with "convenient calculation" is accurate and easy-to-do so the
      method is appropriate for clinical application.

PMID- 12205924
TI  - [The satisfaction, efficacy, and relative factors for Norplant in countryside of
      Sichuan].
AB  - A total of 1473 Norplant users in the countryside of Sichuan Province were
      investigated to present a multivariate analysis of satisfaction, side effect, and
      efficacy for Norplant. The results showed that contraceptive efficacy rate,
      continuation rate, prevalence rate of side effects and satisfactory rate were
      99.3%, 90.6%, 86.4%, and 69.7%, respectively. The logistic regression analysis
      showed that the variables significantly contributing to satisfaction were the
      user's knowledge about Norplant, the user's voluntary choice of Norplant, and the
      spouse's satisfaction. The satisfaction was associated with continuation and the
      prevalence of side effects. It is concluded that Norplant is efficacious and
      satisfactory to a certain extent among the users in rural Sichuan; its
      continuation rate is high but the prevalence of side effects is noticeable. For
      the wide application of Norplant in the countryside, it is important to
      strengthen propagation and education.

PMID- 12205925
TI  - [Epidemiological survey of conjoined twins in China].
AB  - A descriptive study was conducted to investigate the incidence and
      epidemiological characteristics of conjoined twins in China. From 1988 to 1992,
      data were collected from more than 500 hospital-based units involved in a
      monitoring program and were analyzed by the National Center for Birth Defects
      Monitoring. The monitored subjects were the hospitalized births from 28 weeks
      gestation to a period within 7 days after delivery. 106 conjoined twins were
      found in 3,246,408 births with an incidence rate of 0.3/10,000. The highest rate
      was 0.8/10,000 in He'nan Province and Anhui Province(P < 0.05), and the lowest
      0.1/10,000 in Beijing and Jilin Province (P < 0.01). Conjoined twins were more
      common in females; the ratio of female to male was 2 to 1. No difference was
      observed between the urban and rural areas. The prenatal mortality was as high as
      915@1000. Only 31.13% conjoined twins were diagnosed prenatally. The results
      indicate that the incidence of conjoined twins in China is not different from
      that in other countries, but the work of prenatal diagnosis in China should be
      improved.

PMID- 12205926
TI  - [On the problems of fitting linear regression models for hierarchically
      structured data in medical research].
AB  - There are a large number of the hierarchically structured data in the field of
      medical sciences, which have been analyzed usually by conventional linear
      regression models. The objective of this paper is to explore the problems and the
      relationship of parameter estimates of the three common linear regression models
      in fitting the hierarchically structured date, and the correction of the
      precision of parameter estimates. It is shown that the estimate of parameter and
      it's precision of linear regression models is related to the variation of
      independent variable between and within level 2 units, and the difference of
      residual estimates is associated with the difference of parameter estimates. The
      three common linear regression models are all inappropriate for the
      hierarchically structured data, but the standard error of the level 1 combined
      model can be corrected by variance inflation factor in conditions.

PMID- 12205927
TI  - [Application of intraclass correlation coefficient to reliability assessment].
AB  - To evaluate the reliability of questionnaire and expound the simple method of
      calculating and testing the intraclass correlation coefficient (ICC), the authors
      gave an example of how to simply calculate and conduct the hypothesis testing of
      ICC by using the analysis table of variance. The results demonstrated a high test
      retest reliability of the illustrative questionnaire. By using ANOVA table, the
      calculation and hypothesis testing of the ICC is easy to do. The method can be
      used in the analysis of quantitative data, and categorical data as well.

PMID- 12205928
TI  - [Changes of lipids metabolism during gallstone formation in rabbit model and the
      effects on these changes by high density lipoprotein preparation injection].
AB  - To study the changes of lipids metabolism during gallstone formation and the
      effects fo the exogenous high-density lipoprotein (HDL) preparation on the
      formation of gallbladder stone in rabbit model in which the stones were induced
      by high-cholesterol (HC) diet. The plasma lipids, the bile cholesterol, the
      activity of plasma lecithine cholesterol acyltransferase (LCAT), the bile acids
      in both bile and plasma, and the incidence of stone formation were investigated
      in the control group, HC group, and HC + HDL group (in this group the rabbits
      were given HDL preparation intravenously regularly). The results showed that the
      lipids metabolic disorder was characterized by a large amount of cholesterol
      accumulated in the rabbit's body and when the liver cleaned the accumulated
      cholesterol, the ratio of biliary cholesterol to bile acids was significantly
      increased. The latter could cause the production of lithogenic bile. Thought HDL
      preparation could decrease hepatic cholesterol and increase the level of plasma
      HDL2-C and the activity of LCAT, it could not lower the incidence of gallstone
      formation. The results suggest that the HDL preparation had some effects on
      lipids metabolism, but no significant effect on gallstone formation in rabbit
      model has been evidenced, so the problem awaits further studies.

PMID- 12205929
TI  - [Polymorphism at cholesteryl ester transfer protein gene loci in patients with
      gallstone].
AB  - This study was designed to reveal the association between the polymorphism of
      cholesteryl ester transfer protein (CETP) gene loci and gallbladder stone
      disease. By means of polymerase chain reaction (PCR) and restriction fragment
      length polymorphisms (RFLEs) of CETP taqIB, BamHI genes were examined in 104
      patients subjected to cholecystectomy for symptomatic gallstone disease and 68
      healthy controls. The distribution of CETP taqIB polymorphism in the patients
      with gallstones differed significantly from that of the controls. The B1 allele
      and B1B1 jects were more frequently revealed in patients with gallstones (0.523,
      vs 0.346, 0.288 vs 0.1176, P < 0.05). The B2 allele and the B2B2 jects appeared
      in the controls more frequently (0.654 vs 0.477, 0.4264 vs 0.242, P < 0.05). The
      H1 allele, H2 allele and H1H1 genotypic, H2H2 genotypic frequencies of the
      patients with gallstones were not significantly different from those of the
      controls (P > 0.05). The results suggest that B1 allele is the major gene in the
      patients with gallstones, and B2 allele is more frequently revealed in the
      controls.

PMID- 12205930
TI  - [In vitro hepatic targeting tendency of galactosyl-anti CD3 McAb-TILS].
AB  - This study was undertaken to enhance the hepatic targeting tendency of tumor
      infiltrating lymphocytes (TILs) and hence to lower the recurrence rate of primary
      liver cancer after hepatectomy. Galactosyl-anti CD3McAb-TILs were prepared and
      then were incubated together with hepatocytes. Their interaction through
      asialoglycoprotein receptor-mediated mechanism was observed under the inverted
      phase contrast microscope. The carbohydrate density of galactosyl-anti CD3McAb
      and the combining rate of galactosyl-anti CD3McAb with TILs were measured. The
      results revealed that galactosyl-anti CD3 McAb-TIL obviously were adhered to
      hepatocytes. The carbohydrate density of galactosyl-anti CD3McAb was 62.18, and
      the combining rate of galactosyl-anti CD3McAb with TILs was 97.9%. The results
      suggested that in vitro hepatic targeting tendency of galactosyl-anti CD3McAb
      TILs was satisfactory, and that the carbohydrate density of 62.18 and the
      combining rate of 97.9% ensured the effective use of TILs.

PMID- 12205931
TI  - [Expression of C-erbB-2 protein in breast cancer and its clinical significance].
AB  - In order to understand the expression of C-erbB-2 protein in breast cancer and
      its clinical significance, we examined the expression of C-erbB-2 protein in 106
      breast carcinomas by using the immunohistochemical techniques LSAB. The results
      showed that the positive rate of C-erbB-2 expression was 63.21% (67/106). The
      overexpression of C-erbB-2 protein related negatively with survival. 81.63% of
      the cases with overexpression of C-erbB-2 protein survived < or = 5 years and
      34.29% survived > 10 years. There were significant associations of C-erbB-2
      overexpression with advanced clinical stage, high histological grade, and
      positive axillary node status in breast cancers. All of these findings suggested
      that overexpression of C-erbB-2 protein might be an important prognostic factor
      and the detection of C-erbB-2 protein might be arranged as a regular pathological
      examination in the cases of breast cancer.

PMID- 12205932
TI  - [Protective and therapeutic effects of intravenous-immunoglobulin on viral
      myocarditis].
AB  - This study was conducted to determine whether the administration of domestically
      manufactured intravenous-immunoglobulin (IVIG) could prevent or alleviate
      myocarditis in mice. Male BALB/c mice were randomized into two groups for
      protection group (P) and therapy group (T), and each of the two groups was
      subdivided into 4 groups (1, 2, 3 and c). A 7-day protocol with daily IVIG dosage
      of 200 mg/kg, 500 mg/kg and 1 g/kg for groups, P1, T1, P2, T2 and P3, T3
      respectively was designed. In the experiment, the mice were inoculated with
      Coxsackie virus B3. The prevention groups (P1, P2, P3) received IVIG in the week
      immediately after the inoculation; the therapy groups (T1, T2, T3) received IVIG
      in the second week after the inoculation. All the animals were observed for 14
      days. The results showed that all mice in groups P2 and P3 survived and the
      pathological studies revealed no myocarditis change. By the end of observation,
      however, 7 mice in the control group (Pc) died with severe myocarditis changes
      while one mouse in group P1 died with only slight inflammatory lesions in the
      heart. The survival rates of groups P1, P2 and P3(95%, 100% and 100%) differed
      significantly from the control (65%) statistically (P < 0.05). Similarly, the
      results of computed image analysis demonstrated that a significant difference
      existed between the cardiac lesions of groups P1 and Pc in severity (P < 0.05).
      The survival rates were 80.0%, 93.3%, 93.3% and 53.3% for groups T1, T2, T3 and
      Tc respectively (P < 0.05 for T2, T3 v. s. control), yet the hearts and
      heart/body weight ratios of T2 and T3 were significantly smaller than those of
      control, pathological study was supportive which showed slight (T2 and T3) or
      mild (T1) lesions of the heart in comparison with the control. These results
      demonstrate that Chinese made IVIG has definite protective and therapeutic
      effects on the mice infected with CVB3.

PMID- 12205933
TI  - [Activation of neutrophil and its relation to neutrophil-endothelial cell
      adherence].
AB  - Neutrophil was activated by chemotactic tripeptide N-formyl-methionyl-leucyl
      phenylalanine(fMLP) of different concentration. The activation rate was tested by
      the method of nitroblue tetrazolium reduction. Using flow chamber system, we
      quantitatively studied the properties of neutrophil adhesion to human umbilical
      vein endothelial cell (HUVEC) under different shear stress. The results showed
      that the activation rate of neutrophil significantly increased with increase of
      fMLP concentration that the adhesion rate of neutrophil pretreated with fMLP
      decreased with the gradual increase of shear stress, such a change was also found
      in the control group; and that the adhesion rate of neutrophil to HUVEC increased
      with the increase of activation rate of neutrophil, but the adhesion rate had a
      tendency to decrease when shear stress increased. These indicated that shear
      stress induced by bloodstream might play an important role in inhibiting
      neutrophil-endothelial cell adherence in vivo and the enhanced activation of
      neutrophil could increase neutrophil-endothelial cell adherence.

PMID- 12205934
TI  - [Leukocyte adhesion molecule expression and circulating ICAM-1, E-selectin levels
      during cardiopulmonary bypass in patients undergoing valve replacement].
AB  - The objectives of this study were to measure leukocyte adhesion molecule
      expression, assess the possibility of evaluating the serum levels of the soluble
      form of endothelium adhesion molecule as an alternative for endothelia cell
      activation, and analyze the correlation and regression between leukocyte adhesion
      molecule expression and soluble endothelium adhesion molecule levels during
      cardiopulmonary bypass (CPB) in patients undergoing valve replacement. Twelve
      adult patients were included in this study. The extracorporeal circuit was primed
      with Ringer's lactate. After systemic heparinization (300 IU/kg), CPB was
      initiated with a bubble oxygenator. Patients were cooled to about 28 degrees C,
      at that temperature, aorta was clamped and cold crystalloid cardioplegia was
      delivered into aortic root. The activatal clotting time was maintained at greater
      than 450 seconds. 1-1. 3 mg of protamine was administered for each 100 IU of
      heparin given prior to CPB. Peripheral blood was collected at the day prior to
      surgery and the morning of postoperative days 1, 2, 5, and 7 for determination of
      the expression of leukocyte CD11a, CD18, CD11a/CD18, CD11b, CD11b/CD18
      (immunofluorescent flow cytometry) and the plasma soluble intercellular adhesion
      molecule-1(sICAM-1), soluble E-selectin (sE-selectin) (enzyme-linked
      immunoabsorbent assay). CPB caused a sustained increase in the leukocyte CD11a,
      CD18, CD11a/CD18, CD11b/CD18 expression and the plasma sICAM-1, sE-selectin
      levels in patients (P < 0.05). Upregulation of the leukocyte adhesion molecule
      expression and increase of the circulation endothelium adhesion molecule levels
      lasted at least 2 days after surgery (P < 0.05) except CD11a. There were
      correlation and regression between leukocyte adhesion molecule expression and
      soluble endothelium adhesion molecule levels (r = 0.91-0.99, P = 0.0322-0.0005; Y
      = -1377.06-44.64 + 1.49-14.78a to Y = 44.64 + 1.49a). These results suggest that
      CPB causes obvious leukocyte-endothelia interactions, that the expression of
      these adhesion molecules are presented by means of receptor-ligand form, and that
      the measurement of sICAM-1 and sE-selectin may well be used as a marker of
      endothelial cell activation.

PMID- 12205935
TI  - [Clinical analysis of percutaneous balloon mitral valvotomy in 1063 patients].
AB  - This article reports the clinical study of 1063 patients who underwent
      percutaneous balloon mitral valvotomy (PBMV) and 1043 patients among them who did
      successfully (98.2%). After the procedure, left atrial mena pressure fell from
      3.19 +/- 1.06 kPa to 2.00 +/- 0.93 kPa (P < 0.001), mitral pressure gradient
      decreased from 2.79 +/- 1.20 kPa to 1.33 +/- 1.06 kPa (P < 0.001). Disappearance
      of diastolic murmur and significant improvement of cardiac function were
      achieved. Among the 20 failed cases, there were cardiac perforation and/or
      pericardial tamponade (8 cases), cerebral embolism (3 cases), severe mitral
      regurgitation (3 cases), atrial septal defect (2 cases) and discontinuance of the
      procedure due to various causes. The short-term outcome of PBMV is satisfying, so
      it can replace the surgical closed valvotomy as an effective treatment for
      selected patients with mitral stenosis.

PMID- 12205936
TI  - [Expression of vascular endothelial growth factor in brain astrocytoma and its
      clinical evaluation].
AB  - Angiogenesis is often involved in tumor growth. Neovascularization plays an
      important role in the prognosis of patients with brain astrocytoma. Vascular
      endothelial growth factor (VEGF) has been known as the potent angiogenetic factor
      and mitogen. To gain a deep insight into the possible relation between expression
      of VEGF and pathological characterization/prognosis in brain astrocytoma, the
      authors investigated 107 cases of brain astrocytoma and 25 cases of normal brain,
      tissue via a combination of immunohistochemical staining of paraffin-embedded
      tissue and follow-up survey. The results showed that the positive staining rate
      and PU (positive unit) were obviously higher in astrocytoma than that in normal
      brain (86.92% vs 16.00%, P < 0.05), that the value of the positive staining rate
      and PU in astrocytoma corresponded closely with its pathological grade and stage
      (P < 0.01), and that the survival rates (6, 12, 24 months) for the patients
      suffering from astrocytoma gradually decreased when the VEGF positive rate
      increased. These suggest that the expression of VEGF may have close relationship
      with brain astrocytoma and the measurement of the VEGF expression may provide
      another potential standard for judgement about pathological grade/stage and
      clinical prognosis in brain astrocytoma.

PMID- 12205937
TI  - [A study of Bcl-2 expression in normal endometrium and endometrial carcinoma].
AB  - To make an initial inquiry into the correlation of development and prognosis with
      the expression of Bcl-2 protein in endometrial carcinoma, we detected the Bcl-2
      protein expression in 40 normal and 60 malignant samples of the endometrium by
      means of an immunohistochemical technique. We observed that Bcl-2 expression
      varied with menstrual cycle, becoming stronger in proliferative phase and then
      declining in secretory phase. Bcl-2 expression in endometrial carcinoma was much
      weaker than that in normal endometrium, and Bcl-2 was particularly expressed in
      adenoacanthoma, papillary adenocarcinoma and simple adenocarcinoma. The higher
      grade and stage were, the stronger Bcl-2 expression was (P < 0.01). In 5 cases of
      endometrial carcinoma with hyperplastic endometrium, Bcl-2 expression of
      carcinoma was obviously weaker than that of hyperplastic endometrium. So we
      conclude that Bcl-2 overexpression may contribute to the formation of
      hyperplastic endometrium, that obvious reduction of Bcl-2 expression in
      endometrial carcinoma may promote apoptosis of cells, and that Bcl-2 over
      expression may be associated with good prognosis.

PMID- 12205938
TI  - [A pharmacokinetic study of teniposide in intraperitoneal chemotherapy of ovarian
      cancer].
AB  - The objectives of this study were to determine the characteristics of
      pharmacokinetics of teniposide (VM-26) instilled intraperitoneally with three
      dosages (100 mg, 150 mg and 200 mg) and to evaluate its toxicity. Twelve patients
      with ovarian cancer were divided into three groups: teniposide 100 mg i.p., 5
      patients; teniposide 150 mg i.p., 5 patients; and teniposide 200 mg i.p., 2
      patients. Samples of ascitic fluid, blood and urine were collected after
      administration of these drugs in 24 hours. Concentrations of teniposide were
      determined with high-performance liquid chromatographic procedure. The results
      showed that the data collected from peritoneum and plasma were found to conform
      to a two-compartment open model. The peak concentration (Cmax) and the area under
      the curves (AUC) in peritoneal cavity and plasma were dose-dependent. The ratios
      of Cmax and AUC between peritoneal fluid and plasma varied within 13.46 +/- 1.89
      and 7.65 +/- 2.03 respectively. The elimination half-lives (T1/2 beta) in the
      peritoneum and plasma of teniposide were 5.28 +/- 0.95 and 6.64 +/- 2.73 hours
      respectively. The volume of peritoneal distribution and its clearance were lower
      than those of plasma (P < 0.001). The side effects were mild and were not
      dependent on drug dosage. The results suggest that teniposide as an
      intraperitoneal therapeutic agent offers some advantages in the treatment of
      ovarian cancer. The tumor tissues and peritoneal growths could be bathed in a
      high concentration of teniposide. Teniposide is safe, reasonable in
      intraperitoneal chemotherapy and shows prospects in the treatment of ovarian
      cancer.

PMID- 12205939
TI  - [Characteristics of pulmonary function changes in cough variant asthma and
      chronic asthmatic bronchitis].
AB  - To understand with greater clearness the characteristics of pulmonary function
      changes in patients with cough variant asthma (CVA) and patients with chronic
      asthmatic bronchitis(CAB), 30 cases of CVA and 25 cases of CAB were examined by
      pulmonary function test and were compared clinically. The results showed the
      differences in medical history and some clinical manifestations between the two
      groups were significant (P < 0.05). The expiratory flow parameters (PEF, MMEF,
      FEV1) of pulmonary function test in CVA were generally normal; these parameters
      in CAB group, however, were obviously decreased. The airway challenge test
      uncovered a 100% positive reaction in CVA patients, but only less than 1/4 of the
      patients with CAB showed positive reaction. Furthermore, the positive
      concentration of challenge agents (Mch) required for CVA group was 1/4.7 of the
      ones for CAB group, and the positive Mch concentrations of the two groups seldom
      crossed each other. It is concluded that some clinical manifestations of CVA and
      CAB were significantly different, although many similarities between them do
      exist; the MEFV curve in pulmonary function test and the airway challenge test
      can be used to differentiate them well.

PMID- 12205940
TI  - [A pharmacognostical study on herba Spirodelae and its adulterants].
AB  - OBJECTIVE: To Study the characteristics of Herba Spirodelae(Spirodela polyrrhiza)
      and its adulterants S. oligorrhiza and Lemna minor for identification. METHOD:
      The characteristics were compared and identified morphologically and
      histologically. RESULT: The morphological and histological characteristics of S.
      polyrrhiza, S. oligorrhiza and L. minor are different from each other. Several
      tables, keys and drawings are given. CONCLUSION: The main macroscopical and
      microscopical characteristics can be used fo differentiate S. polyrrhiza from its
      adultrants.

PMID- 12205941
TI  - [Survey on traditional medicinal resources of Uncaria distributed in China].
AB  - OBJECTIVE: To make clear the botanical origin of medicinal Uncaria distributed in
      China and the situation of its use in folk medicines. METHODS: Collecting data
      and making on-the-spot investigation. RESULTS: There are thirteen medicinal
      plants which belong to Uncaria genus, and ten of them are commercially available.
      A clear idea was obtained of their geographical distribution, distribution
      features and practical experiences in folk application. CONCLUSION: This
      investigation is helpful in further researching and exploring the resources of
      Uncaria for medical use, as well as provides a scientific basis for production,
      management and safe use of crude drugs.

PMID- 12205942
TI  - [Studies on the effects of space flight on Carthamus tinctorius L].
AB  - OBJECTIVE: To substantiate the effects of space condition of medicinal plants.
      METHODS: The seeds of Carthamus tinctorius were sent to space in retrievable
      satellites. After returning to earth, the seeds were stored at 0-4 degrees C, and
      cultured in the test field in the spring of next year. The peroxidases, soluble
      proteins and ultrastructure of leaves were studied in flowering stage. RESULTS:
      The peroxidase activity of the flight group was lower than that of the earth
      controlled group, and the protein content of the flight group was higher than
      that of the earth controlled group. The main bands in electrophoresis patterns of
      peroxidases and proteins were alike, and some bands were different. Some changes
      could be observed in the ultrastructure of chloroplast between the flight group
      and the earth controlled group. CONCLUSION: Space environments have some effect
      on Carthamus tinctorius. The results of this experiment are consistent with those
      of the previous experiment.

PMID- 12205943
TI  - [The extraction of DNA from milligram amounts of wild mountain ginseng tissues].
AB  - OBJECTIVE: To keep wild mountain ginseng, a rare medicinal remedy, as intact as
      possible when extracting DNA from it, a new way to extract DNA has been explored.
      METHOD: The CTAB method was improved and a simple and direct way was developed.
      RESULT: From 0.001 g of dried samples of ginseng root DNA was obtained in an
      amount up to 2.25 micrograms. CONCLUSION: The RAPD fingerprinting generated by
      this DNA is as good as that by CTAB method. This new method may also be used for
      extraction of other precious Chinese medicinal materials.

PMID- 12205944
TI  - [A study on the quality criteria for wushicha capsules].
AB  - OBJECTIVE: To build up the quality criteria for Wushicha capsules. METHOD:
      Rhizoma Atractylodis, Cortex Magnoliae Officinalis, Rhizoma Chuanxiong, Herba
      Pogostemonis in Wushicha capsules were identified by TLC. The contents of
      magnolol in the preparation were determined by GC. RESULT: These methods are
      simple and accurate. CONCLUSION: These methods can be used for the quantitative
      analysis of Wushicha capsules.

PMID- 12205945
TI  - [Research on petroleum ether extract of rhizoma Drynariae].
AB  - OBJECTIVE: To study the petroleum ether extract of Rhizoma Drynariae. METHOD:
      Solvent extraction silica gel column isolation, and structure elucidation by
      physico-chemical evidence and spectral analysis. RESULT: Three compounds were
      isolated and elucidated as fern-9(11)-ene, hop-22(29)-ene and cyclolaudenol.
      CONCLUSION: All the three compounds are triterpenoids.

PMID- 12205946
TI  - [Studies on chemical constituents of Ilex Merr].
AB  - OBJECTIVE: To further probe into the chemical composition of Ilex hainanensis.
      METHOD: Compound isolation was affected on the basis of the EtOAc soluble
      fraction of the ethanolic extract from the leaves of the plant. RESULT: Four
      compounds were obtained and by physico-chemical and spectroscopic methods
      identified as ursolic acid, ilexgenin A, ilexsaponin A1 and beta-sitosterol-3-O
      beta-D-glucoside. CONCLUSION: All the four compounds were isolated from the plant
      for the first time.

PMID- 12205947
TI  - [Isolation and identification of two flavonoids from Taraxacum mongolicum Hand.
      Mazz].
AB  - OBJECTIVE: To study the chemical constituents of Taraxacum mongolicum. METHOD:
      Compounds were separated by column chromatography on silica gel and polyamide,
      and their structures were determined by spectral analysis and chemical evidence.
      RESULT: Two flavonoid compounds were separated and elucidated as isoquercitrin
      and hyperin. CONCLUSION: These two compounds were isolated from the plant for the
      first time.

PMID- 12205948
TI  - [Studies on chemical constituents of Euphorbia ebracteolata Ilayata].
AB  - OBJECTIVE: To search for the effective anti-epilepsiy components from the Chinese
      folk drug Langdu, the root of Euphorbia ebracteolata. METHOD: Chromatography and
      spectroscopic analysis were used to isolate and elucidate the chemical
      constituents in the plant. RESULT: Four compounds, namely 10-nonacosanol, 24
      methylenecycloartanol, stigmasterol and dacosterol have been isolated from the
      precipitate of the plant's methanol extract. CONCLUSION: 10-nonacosarnol and 24
      methylenecycloartanol were obtained from the root of E. ebracteolate for the
      first time.

PMID- 12205949
TI  - [Influence of functional groups of huatanyuxin decoction on Ca2+ transmembrane
      influx in rat aorta].
AB  - OBJECTIVE: To study the Ca2+ antagonistic effect of functional groups of
      Huatanyuxin decoction. METHOD: The 45Ca transmembrane influx technique was used
      to measure the Ca2+ blocking effect of leak, receptor-operated Ca2+ channel (ROC)
      and potential-dependent Ca2+ channel (PDC) in rat aorta. RESULT: ROC and PDC
      could be blocked when the complex prescription was used at concentrations of 0.5
      5 mg/ml. Among the functional groups, Huoxue group (activating blood) and Xinqi
      group (promoting and normalizing flow of vital energy) showed better Ca2+
      antagonistic effect. CONCLUSION: The mechanism of therapeutic effect of
      Huatanyuxin decoction may be related to its Ca2+ blocking effect similar to
      verapamil.

PMID- 12205950
TI  - [Cerebral protective effects of some compounds isolated from traditional Chinese
      herbs].
AB  - OBJECTIVE: To study the cerebral protective effects of some compounds isolated
      from traditional Chinese herbs. METHOD: Laser microcirculation dynamic analyzer
      and cultured rat cortical neurons were used. RESULT: Pueraria lobata
      flavonoids(LPF), Panax notoginseng saponins(PNS), oxymatrine, anisodamine and
      berberine could dilate microvessels and increase the cerebral blood flow of
      anesthetized mice's meninges. LPF, PNS, oxymatrine, and anisodamine also
      accelerated the flow of blood. Oxymatrine, like anisodamine, increased quantities
      of erythrocytes in high frequency movements. PNS could protect cultured rat
      cortical neurons from glutamate neurotoxicity. CONCLUSION: LPF, PNS, oxymatrine,
      anisodamine and berberine have certain protective effects on brain, but differ in
      mechanisms of action.

PMID- 12205951
TI  - [Advances in the study on the treatment of osteoporosis with Epimedium
      brevicornum and its compound prescription].

PMID- 12205952
TI  - [Species and distribution of Chinese medicinal plant Caesalpinia].
AB  - OBJECTIVE: To gain a clear idea on the resources of medicinal plant Caesalpinia
      in China. METHOD: Conducting field investigation and consulting related specimens
      and data. RESULT: The distribution, growing environment and medicinal parts of 14
      species of Caesalpinia have been clarified, and a key for their identification is
      given. CONCLUSION: A scientific basis for further study of the medicinal plant
      Caesalpinia in China has been provided.

PMID- 12205953
TI  - [Species evolution of Chinese flos Dendranthematis].
AB  - OBJECTIVE: To probe into the history and current situation and main producing
      areas of different species of Chinese Flos Dendranthematis. METHOD: On-the-spot
      investigation, cultivation observation and literature study. RESULTS:
      Morphological characteristics of different species of Flos Dendranthematis were
      clarified, and the historical changes of these species were studied. CONCLUSION:
      Congju is related to Hangju. Boju is related to Huaiju. Jiju and Qiju, and Chuju
      is a distinctive species. These findings are important for the cultivation and
      processing of Chinese Flos Dendranthematis.

PMID- 12205954
TI  - [Effect of growth period, storage time and varieties on the contents of main
      active constituents of Curcuma longa L. in rhizome].
AB  - OBJECTIVE: To provide criteria for selection, storage and cultivation of the
      rhizome of Curcuma longa. METHOD: Field observation and sample analysis on the
      rhizome. RESULT: The contents of curcuminoids and essential oils in mother and
      daughter rhizome went up with the progress of plant development. The contents of
      curcuminoids reached the maximum in early September and early October. The
      contents of essential oils in mother rhizome reached the maximum in early
      September. The contents of curcuminoids and essential oils in the rhizome varied
      with the species and went down with the increase of storage years. CONCLUSION:
      The rhizome should be collected when leaves of the plant have just withered. The
      suitable storage time is three years.

PMID- 12205955
TI  - [Studies on variations of alkaloids in zhebeimu (Fritillaria thunbergii Miq.) by
      improved colormetric determination].
AB  - OBJECTIVE: To find out the seasonal variation of active alkaloids in Zhebeimu(F.
      thunbergii) collected from Zhejiang Ninbo and Jiangsu Nantong, and confirm the
      suitable harvesting time for the crude drug. METHOD: Determining the alkaloid
      contents in the samples of Zebeimu collected monthly from the above-said
      twoplaces by improved colormetric method. RESULT: The alkaloid accumulation
      patterns of the samples from two places are very similar, with the highest
      contents appearing in samples collected in January of February, and the absolute
      amounts in samples harvested in May. CONCLUSION: The optimum time for harvesting
      Zhebeimu is in May.

PMID- 12205956
TI  - [Comparison of semi-bionic extraction and water extraction in extraction of
      chemical constituents from processed cortex Phellodendri].
AB  - OBJECTIVE: To Study the granulation of processed Cortex Phellodendri. METHOD:
      Take berberine, total alkaloids and dry extract as indexes to compare the semi
      bionic extraction (SBE) with water extraction (WE). RESULT: In 5 kinds of
      phellodendron bark solution, berberine, total alkaloids and dry extract obtained
      by SBE are much better than those obtained by WE. CONCLUSION: In the preparation
      of oral granules from processed Cortex Phellodendri, SBE is superior to WE, when
      the pH value is adjusted by HCl solution to 1.0 in the first decoction, adjusted
      by saturated Ca(OH)2 solution to 7.0 in the second decoction and to 10.0 in the
      third decoction respectively.

PMID- 12205957
TI  - [A study on chemical components of Tetrastigma hemsleyanum Diels et Gilg. Native
      to China].
AB  - OBJECTIVE: To investigate the chemical constituents of Tetrastigma hemsleyanum
      native to China. METHOD: Compounds were separated by column chronatography with
      silica gel and elucidated by chemical evidence and spectral analysis. RESULT:
      Four compounds were isolated from the petroleum ether extract. Their structures
      were identifies as taraxerone, taraxerol,beta-sitosterol and ergosterol.
      CONCLUSION: These compounds were isolated from the plant for the first time.

PMID- 12205958
TI  - [Studies on chemical constituents from fruits of Trichosanthes kirilowii Maxim].
AB  - OBJECTIVE: To study the chemical constituents of methanol extract from the dried
      ripe fruits of Trichosanthes kirilowii. METHODS: Silica gel column
      chromatographic technology and Sephadex G-10 gel filtration were employed to
      separate and purify the methanol extract, and the compounds obtained were
      elucidated by means of IR, MS, 1HNMR and authentic specimens. RESULT: Palmitic
      acid, stigmast-7-en-3 beta-ol, stigmast-7-en-3-O-beta-D-glucopyranoside,
      galactonic acid gamma-lactone and galactose were isolated and elucidated.
      CONCLUSION: All the compounds were obtained from the fruit s of T. kirilowii for
      the first time.

PMID- 12205959
TI  - [Chemical studies on the polysaccharide in fructus Corni].
AB  - OBJECTIVE: To study the tonic constituents in Fructus Corni, the pulp of Cornus
      of ficinalis. METHOD: Hot-water extraction, ethanol precipitation and column
      chromatography on DEAE-cellulose and Sephadex G-200 were used to isolate and
      purify the polysaccharides in Fructus Corni. HPGPC was used to determine the
      purity and measure the mean molecular weight of the polysaccharides. TLC, PC, GC,
      GC-MS, 13CNMR, partial acid hydrolysis and permethylation to elucidate the
      structures. RESULT: A water-soluble polysaccharide with mean molecular weight of
      2.47 x 10(14), named Co-4, was obtained. It's main chain was (1-->4) linked beta
      D-glucan, with branching points at position 6. CONCLUSION: A thorough study on
      the polysaccharides of Fructus Corni has been made for the first time and the
      structure of Co-4 has been elucidated.

PMID- 12205960
TI  - [A study on chemical composition of Gardenia sootepensis Hutch--quantitative
      determination of iridoid compounds by RP-HPLC].
AB  - OBJECTIVE: To determine the iridoid contents in Gardenia sootepensis. METHODS:
      Using RP-HPLC with geniposidic acid, geniposide and scandoside methyl ether as
      standards. RESULT: According to the selected chromatographic conditions, the
      linear ranges of geniposidic acid, geniposide and scandoside methyl ether were
      0.097-0.606 microgram, 0.0638-3.990 micrograms and 0.198-1.239 micrograms,
      respectively. The average recoveries of these three compounds were 100.0%, 99.9%
      and 100.1%, and RSD 1.23%, 1.38% and 1.53% (n = 5) respectively. CONCLUSION: The
      method is easy, rapid, and reproducible.

PMID- 12205961
TI  - [Studies on pharmacological junctions of hairy root of Astragalus membranaceus].
AB  - OBJECTIVE: To investigate the effect of hairy root of Astragalus
      membranaceus(HRA). METHOD: HRA were given 10 g/kg per day for 50 days to aged
      mice treated with D-galactose, and the effect on memory and antioxidant functions
      were estimated. After administration of HRA 10 g/kg for four days, anti-ischemia
      reperfusion kidney model of rat was prepared. The kidney function, activity of
      superoxide dismutase (SOD) and content of malondialdehyde(MDA) in kidney were
      examined. Mice with immunosuppression induced by cyclophosphamide were given
      orally HRA 10 g/kg for 12 days. The activity of natural killer (NK) cells was
      measured. RESULT: HRA improved the memory, raised SOD activity in brain and
      liver, decreased the MDA content in the liver of aged mice, reduced the MDA
      content in ischemia-reperfusion kidney, decreased the creatinine level in blood
      of rats, and promoted the activity of NK cells in immunosuppressed mice.
      CONCLUSION: Similar to the natural A. membranaceus, HRA has senility-preventing,
      antioxidizing and immunomodulating functions.

PMID- 12205962
TI  - [Research on anti-thrombosis effect of ethanol extract from beheaded leech
      (EEBL)].
AB  - OBJECTIVE: To study the anti-thrombosis effect of EEBL and its possible
      mechanism. METHOD: Using a thrombosis model induced by collagen-adrenaline in
      mice and an artery-vein bypass in rats. The effect of EEBL on erythrocyte
      membrane and thrombocyte membrane fluidity were measured by fluorescence
      polarization. RESULT: EEFL inhibited the thrombosis induced by collagen
      adrenaline in mice and the thrombosis in artery-vein bypass in rats
      significantly. EEBL also enhanced in vitro erythrocyte membrane fluidity and
      thrombocyte membrane fluidity markedly. CONCLUSION: The anti-thrombosis effect of
      EEBL may possibly be associated with the enhancement of fluidity of erythrocyte
      membrane and thrombocyte membrane. There exist anti-thrombosis chemical
      constituents in the body of beheaded leech.

PMID- 12205963
TI  - [Effects of Rg1 on calcium channel of guinea pig ventricular myocytes].
AB  - OBJECTIVE: To evaluate the effect of Rg1 (purified saponin of Panax notoginseng)
      on L-Ca2+ channel of guinea pig ventricular myocytes. METHOD: The whole-cell
      patch clamp recording technique. RESULT: When the holding potential was kept at 
      40 mV, and the cell was depolarized to +40 mV for 150 ms at a frequency of 0.5
      Hz.Rg1 10 mumol.L-1 and 30 mumol.L-1 could not reduce Bay K 8644 and nifedipine
      sensitive L-type Ca2+ inward current (P > 0.05, n = 5). CONCLUSION: Rg1 should
      not be a Ca2+ channel antagonist.

PMID- 12205964
TI  - [Effect of tian ma cu zhi chongji medicinal granules (TMCZCJ) on blood rheology
      in hypostasis rats due to stagnation of liver-qi and learning-memory disorder in
      cerebral ischemia-reperfusion mice].
AB  - OBJECTIVE: To investigate the effect of TMCZCJ on the blood rheology in
      hypostasis rats due to stagnation of the liver-qi and on the learning-memory
      disorder in cerebral ischemia-reperfusion mice. METHOD: The models of hypostasis
      due to stagnation of the liver-qi were made by combining irritation with
      hypodemic injected adrenalin and ice-bath in rats, and the models of learning
      memory disorder were made by repeatedly ligating-reperfusing the bilateral
      carotid in mice. The hypostasis rats and learning-memory disorder mice were
      perorally administrated TMCZCJ(7.7, 15.4 g.kg-1) once a day, for fourteen
      consecutive days. RESULT: TMCZCJ can significantly reduce plasma viscosity, blood
      viscosity and reduced viscosity in hypostasis rats. It can also improve the
      latent learning-memory capability and memory gain-repetition ability in water
      maze for cerebral ischemia-reperfusion mice. CONCLUSION: TMCZCJ can improve
      remarkably blood rheology in hypostasis rats and learning-memory disorder in
      cerebral ischemia-reperfusion mice.

PMID- 12205965
TI  - [Studies on medicinal plant resources of heizhu ravine in Ebian County and their
      sustainable utilization].
AB  - OBJECTIVE: To find out the medicinal plant resources of Heizhu Ravine in Ebian
      County and put forward some principles and measures for their sustainable
      utilization. METHOD: On-the-spot investigation and sample measuring, calculating,
      visiting and assessing. RESULTS: The general situation about these resources was
      expounded. New curative effects of 3 species, distribution and region output of 7
      superiority resource species, 1 plant pesticide species, 3 species suitable for
      extensive propagation and 7 rare species on the verge of extinction were also
      reported. CONCLUSION: This area has more than 1500 species of medicinal plants,
      of which about 300 are original traditional Chinese medicinal herb in most use
      and 1200 are used in folk medicine or as important medicinal raw mAterials.

PMID- 12205966
TI  - [Observation on morphology and histology of Angelica dahurica (Fisch. ex Hoffm.)
      Benth. et Hook. f. var. formosana (Boiss.) Shan et Yuan in the process of in
      vitro cultivation and polyploid induction].
AB  - OBJECTIVE: To explore the relationship between morphogenesis and histogenesis in
      the process of in vitro cultivation of Angelica dahurica f. var. formosana, and
      determine the best period for its polyploid induction. METHOD: In the different
      periods of in vitro cultivation, the explants were obtained and their sections
      observed. When the adventitiousbuds began to differentiate, aqueous solution was
      applied for polyploid induction. RESULT: The adventitious buds were mainly
      externally originated and thus fit for polyploid induction. The most appropriate
      period for induction was around the 38th day of cultivation. CONCLUSION:
      Induction treatment can be used as an effective biotechnological approach to
      adventitious buds in the process of tissue cultivation.

PMID- 12205967
TI  - [Regulation on growth and accumulation of total alkaloid in Leonurus artemisia
      (Lour.)S.Y. Hu by various microfertilizers].
AB  - OBJECTIVE: To trace the effects of various microfertilizers on the growth and
      accumulation of total alkaloid in Leonurus artemisia. METHOD: The total alkaloid
      was determined by spectrophotometry. RESULT: Microfertilizers of different
      concentrations could facilitate the growth of L. artemisia in various degrees and
      Mn-fertilizer of standard concentration and Cu-fertilizer of excessive
      concentration could help raise the output of the plant markedly by up to 43.6%
      and 55.2% respectively. Microfertilizers of different concentrations could
      improve the content of total alkaloid in L. artemisia: Mn-fertilizer of standard
      concentration and B-fertilizer of excessive concentration could enhance the
      contents of total alkaloid up to 2.15% and 2.09% respectively. Mn-fertilizer and
      Cu-fertilizer of standard concentration have been proved very useful in improving
      the resistibility and ability of the plant to survive summer safely, and Fe
      fertilizer of standard concentration could bring the plant an obvious increase of
      output after surviving summer. CONCLUSION: Application of Mn-fertilizer of
      standard concentration is very important for cultivating L. artemisia of
      excellent quality and high output.

PMID- 12205968
TI  - [Analysis on contents of flavonoids and polysaccharides in pollen of Typha
      angustifolia L. and its different processed products].
AB  - OBJECTIVE: To explore the relationship between processing of the pollen of Typha
      angustifolia (TA) and the fluctuation of contents of its effective components-
      flavonoids and polysaccharides. METHOD: The contents of flavonoids and
      polysaccharides in TA and in the different processed products of TA were
      determined by spectrophotometry. RESULTS: The contents of flavonoids in TA
      changed as follows: unprocessed TA(1) > TA stir fried with yellow wine(2) > TA
      stir fried with vinegar(3) > TA dried at 140 degrees C (4) > parched TA(5) > TA
      dried at 180 degrees C (6) > scorched TA(7) > TA dried at 220 degrees C (8) >
      charcoal TA(9). The statistic analysis showed that the flavonoid contents in raw
      TA were significantly different from those in the different processed products (P
      < 0.01) of TA except 2. The polysaccharide contents increased in 4, 5, 6 and 7
      significantly (P < 0.01 or P < 0.05), while decreased in 9 significantly (P <
      0.01). As compared with the polysaccharide contents in 1, no significant changes
      occurred in those in 2 and 8. CONCLUSION: Processing temperature, yellow wine and
      vinegar could stimulate the content change of chemical constituents in TA,
      influencing flavonoids and polysaccharides in different degrees.

PMID- 12205969
TI  - [Qualitative recognition on omitted ingredients in Liuwei Dihuang Pills by
      Bayesian analysis and PRIMA].
AB  - OBJECTIVE: To qualitatively recognize the omitted ingredients in Liuwei Dihuang
      Pills by Bayesian analysis and PRIMA. METHODS: The extracts of the pills were
      analyzed by HPLC, for each object, the areas of nine peaks relative to that of
      the internal standard were selected as classification features. The
      classification model was established on 169 training-set objects. RESULT: The
      classification average accuracy was 100% for four patterns by Bayesian analysis,
      and 99.6% by PRIMA analysis. CONCLUSION: Bayesian analysis and PRIMA analysis can
      be used to classify and recognize the omitted ingredients in Liuwei Dihuang
      Pills.

PMID- 12205970
TI  - [A study on characteristics of transdermal absorption of Radix Angelieae Sinensis
      and its compound formula].
AB  - OBJECTIVE: To investigate the characteristics of transdermal absorption of Radix
      Angelieae Sinensis and its compound formula. METHOD: Using Valia-Chien diffusion
      cell in vitro, and HPLC to determine the content of ferulic acid(FA). RESULT: The
      transdermal permeability coefficient (PC)pf FA, which is the main ingredient of
      Radix Angelieae Sinensis, is greater than that of the monomer (P < 0.01): the PC
      of FA is decreased when Radix Angelieae Sinensis and Salviae Miltiorrhizae are
      used together (P < 0.01): borneol helps enhance the permeation of Radix Angelisas
      Sinensis (P < 0.01); the PC of the compound formula is greater than that of the
      compatibility (P < 0.01). CONCLUSION: The transdermal absorption of an ingredient
      of a traditional Chinese drug is affected not by compatibility, but also by other
      ingredients of the drug. The transdermal absorption of a monomer or a single drug
      could not fully mirror the absorption of a compound formula.

PMID- 12205972
TI  - [Studies on the chemical constituents from Sophora flavescens ait].
AB  - OBJECTIVE: To study the constituents from Sophora flavescens. METHODS: Separating
      the constituents by means of chromatography and identifying their structures on
      the basis of spectral analysis. RESULTS: The five compounds obtained were
      identified as sucrose, lignoceric acid, beta-sitosterol, sinapic acid hexadecyl
      ester and umbelliferon. CONCLUSION: Sinapic acid hexadecyl ester is a new
      compound. These compounds were obtained from the plant for the first time.

PMID- 12205971
TI  - [Study the chemical constituents from Phlomis mongolica turcz].
AB  - OBJECTIVE: To investigate the chemical constituents from the root of Phlomis
      mongolica. METHOD: The chemical constituents were extracted with solvent and
      separated with chromatographic methods. Three compounds were obtained and
      identified by MS, 1H-NMR, 13C-NMR, DEPT, HMQC and HMBC methods. RESULT: The
      structures were established as phloyoside III, phloyoside I and cistanoside B.
      CONCLUSION: These compounds were obtained from P. mongolica for the first time.
      Phloyoside III is a new compound.

PMID- 12205973
TI  - [Studies on the chemical constituents of Patrinia scabiasaefolia fisch].
AB  - OBJECTIVE: To study the chemical compositions of the root and stem of Patrinia
      scabiasaefolia. METHOD: Five compounds were obtained from the ethy acetate
      extract of the root and stem of P. scabiasaefolia by silica column
      chromatography, and identified by chemical and spectroscopic analysis. RESULT:
      The compounds were identified as 2'-acetyl-3-O-beta-arabinopyranosyl-hederagenin,
      28-O-beta-D-glucopyranosyl-oleanolic acid, 3-O-alpha-L-arabinopyranosyl-(1 -->3)
      beta-D-xylopyranosyl-hederagenin and 3-alpha-L-rhamnopyranosyl-(1-->2)-beta-D
      xylopyranosyl-oleanolic acid. CONCLUSION: These compounds were obtained from the
      plant of P. scabiasaefolia for the first time.

PMID- 12205974
TI  - [Effect of Ganoderma polysaccharides on cAMP in murine peritoneal macrophages].
AB  - OBJECTIVE: Investigating the effect of GLB7 on cAMP in murine peritoneal
      macrophages to provide a scientific evidence for the immunomodulatory mechanism.
      METHOD: Cell culture and radio-immunological assay of cAMP were used. RESULT:
      GLB7 increased the production of cAMP in a concentration and time dependent
      manner in murine peritoneal macrophages. CONCLUSION: The immunopotentiating
      effect of GLB7 may be due to the activation of macrophages that leads to the
      increase of cAMP.

PMID- 12205975
TI  - [Textural research on "Shidachuan" and "Shijianchuan" in "Ben Cao Gang Mu Shi Yi"
      (a supplement to the compendium of materia medica)].
AB  - OBJECTIVE: To investigate the historical origins of folk herbal medicines
      "Shidachuan" and "Shijianchuan" METHOD: The origins of "Shidachuan" and
      "Shijianchuan" were confirmed by textural research and investigation of
      therapeutic effects. RESULTS: In "Ben Cao Gang Mu" (the Compendium of Materia
      Medica) "Shidachuan" was not recorded, and "Shijianchuan" was listed only as a
      medicine of "nomination without use", with the habitat and morphology being
      blank. CONCLUSION: The "Shidachuan" which was originally recorded in "Ben Cao
      Gang Mu Shi Yi" (A Supplement to the Compendium of Materia Medica) should be
      "Longyacao" (Agrimonia pilosa) of Rosaceae family. "Shijianchuan" should be
      "Guizhencao" (Bidens bipinata) of Compositae family instead of "Huashuweicao"
      (Salvia chinensis) of Labiatae family. The herbal medicine recorded as
      "shijianchuan" in "Chinese Pharmacopoeia" is the very species of Salvia
      chinensis, which is considered as a new rising species of "Shijianchuan".

PMID- 12205976
TI  - [A probe in good agricultural practice for traditional Chinese drugs].
AB  - OBJECTIVE: To provide some scientific reference for the good agricultural
      practice (GAP) for traditional Chinese drugs (TCDs). METHOD: Based on an
      integrated analysis of the factors bearing on the output and quality of TCD along
      with a study on the possible pollution sources of TCDs, some initial idea
      concerning the research and scope of GAP has been outlined. RESULT AND
      CONCLUSION: GAP for TCDs should be designed to incorporate large-scale production
      bases, standardization of drug varieties, optimization of planting techniques,
      rationalization of harvesting and processing, establishment of famous brands for
      quality TCDs, pollution-free production and circulation, efficient coordination
      of production, supply and marketing, etc.

PMID- 12205977
TI  - [A SEM observation on taxonomic and pharmacognostical identification of genus
      murraya produced in China].
AB  - OBJECTIVE: To Observe the morphological characteristics of the leaf epidermis of
      9 Chinese species of genus Murraya and prepare and index for their
      differentiation. METHOD: SEM(scanning electron microscope). RESULT: Sect. Murraya
      was found having with blurred dividing lines on epidermis without ropy
      emblazonry, while sect. Bergera appeared the other way round. CONCLUSION: M.
      kwangsiensis var. macrophylla should be ground under Sect. Murraya as a new
      species, while M. tetramera should be separated from M. euchrestifolia; SEM has
      been proved very useful in the identification, taxonomic and pharmacognostical
      study of Murraya.

PMID- 12205978
TI  - [Pollen morphology identification of five species of medicinal sanguisorba with
      electron microscope].
AB  - OBJECTIVE: To approach a new evidence for identifying various species of Rosaceae
      Sanguisorba, especially for distinguishing S. applanata from S. sitchinese.
      METHOD: The pollens of five species S. officinalis, S. officinalis var.
      longifolia, S. applanata, S. applanata var. villosa and S. sitchinese were
      morphologically identified with electron microscope. RESULTS: The pollens are
      prolate or perprolate, having six colporates and featuring sculptures of small
      caverns and small granules combined. The species are closed to each other in
      pollen morphology, bur display differences in the diameter of pollens, clarity of
      pore membrane and presence or absence of irregular verrucous sculptures.
      CONCLUSION: This paper provides a new evidence for identifying the Sanguisorba.

PMID- 12205979
TI  - [A study on soil suitability for growth of rhizome of Curcuma longa L].
AB  - OBJECTIVE: To seek for the type of soil that influences favorably the yield and
      quality of Curcuma longa. METHOD: Field contrast control experiment, correlation
      analysis, path analysis and cluster analysis were used. RESULT: The rhizome yield
      and quality of Curcuma longa. varied greatly with the types of soil texture.
      There are clear correlations among the soil factors, as well as between the soil
      factors and the rhizome yield and quality of the plant. A regression equation of
      the rhizome yield and soil factors has been built up. CONCLUSION: The soil
      suitable for growing Curcuma longa. can be classified into three types according
      to the results of correlation analysis and cluster analysis.

PMID- 12205980
TI  - [Studies on stimulating components of raw Pinellia ternata (Thunb.) (banxia)].
AB  - OBJECTIVE: To study the stimulating components of raw Pinellia ternata (Banxia).
      METHODS: Used the methods of extracting with various organic solvents; x-ray
      fluorescence spectrometer; scanning electron microanalyzer; oxidation and
      reduction titrations; and ultraviolet spectrophotometry. RESULTS: Experiments
      showed that calcium oxalate hydrate (C2CaO4 x H2O) was one of the stimulating
      components of raw Pinellia ternata, and its shape, and contents related to the
      stimulation of raw Pinellia ternata. After processing, the shape and contents of
      calcium oxalate changed, decreased respectively, and the stimulation of Pinellia
      ternata decreased. CONCLUSION: The needle crystal of calcium oxalate is one of
      the stimulating components in raw Pinellia ternata.

PMID- 12205981
TI  - [A study on chemical constituents in seeds of Crataegus pinnatifida Bge. var.
      major N. E. Br].
AB  - OBJECTIVE: To study the chemical constituents in the seed of Crataegus
      pinnatifida var. major. METHOD: Four compounds were isolated and identified by
      column chromatography and 1H, 13C-NMR data. RESULTS: The compounds obtained were
      identified as protocatechuic acid, gallic acid, catechol and p-hydroxybenzoic
      acid. CONCLUSION: All the compounds were isolated from this plant for the first
      time.

PMID- 12205982
TI  - [GC-MS analysis of volatile constituents of rhizoma Heterosmilacis].
AB  - OBJECTIVE: To extract and analyze the volatile constituents from the dried
      rhizomes of Heterosmilax yunnanensis(A) and H. chinensis(B). METHODS: Qualitative
      and quantitative analysis were made by GC-MS and GC. RESULTS: Forty and forty
      seven constituents were identified from A and B respectively, the identification
      rates being 74.85% and 81.26% respectively. CONCLUSION: The volatile constituents
      of A and B are almost the same, but slightly different in content.

PMID- 12205983
TI  - [Chemical studies on polysaccharides from mycelium of Hericium erinaceum (Bull.
      Ex Fr.) Pers].
AB  - OBJECTIVE: To study the chemical composition and structure of polysaccharides
      from the mycelium of Hericium erinaceum. METHOD: DEAE-cellulose and DEAE-Sephadex
      column chromatography were employed for isolation and purification. Sephadex
      column chromatography and agarose gel electrophoresis were used to measure the
      purity. Gel filtration was employed to measure MW. Acid hydrolysis, enzymolysis,
      GC and spectral analysis etc. were employed for determination of the composition
      and construction of the unique homogeneous polysaccharides. RESULT: The five
      homogeneous polysaccharides were obtained from the mycelium. The main
      compounds(HEPA1, HEPA4 and HEPB2) were identified. CONCLUSION: HEPA1 (MW 62,000)
      is a heteropolysaccharide consisting mainly of glucose. HEPA4 (MW 26,000) is a
      heteropolysaccharide peptide. HEPB2 (MW 12,000) is a heteropolysaccharide
      consisting mainly of glucose. The main linkage of all the afore-said homogeneous
      monosaccharides is alpha-linkage.

PMID- 12205984
TI  - [Determination of oleanolic acid and ursolic acid in spica Prunellae by
      derivative GC method].
AB  - OBJECTIVE: To develop a GC method to determine the oleanolic acid and ursolic
      acid in Spica Prunellae. METHOD: Before GC analysis, the sample was derivatized
      with CH2N2 solution. The GC conditions were as follows: comumn-10% SE-30(2m x
      3mm) and column temperature -270 degrees C. RESULT: The two constituents were
      well separated and had good linearity in the range of 0.0025-0.4000 mg/ml. The
      average recoveries and RSD of oleanolic acid were 93.53% and 3.5%, 94.18% and
      3.0% respectively. CONCLUSION: The method is good for determining oleanolic acid
      and ursolic acid in Chinese medicines.

PMID- 12205985
TI  - [Effect of Boschniakia rossica extract on antioxidative activities in rat hepatic
      preneoplasia induced by diethylnitrosamine].
AB  - OBJECTIVE: To study the antioxidative effect of aqueous fraction of Boschniakia
      rossica(BR) extracted with methanol and fractionated with dichloromethane and
      water. METHOD: Serum activities of superoxide dismutase(SOD),
      malondialdehyde(MDA), glutathione peroxidase (GSH-PX) and glutathione S
      transferase (GST) were investigated in rat with preneoplasia induced by Solt
      Farber protocol under administration with BR extract for 6 weeks. RESULT: Serum
      activities of SOD and GSH-PX rose again in rats administered with BR extract, and
      the increase of GST activity and content of MDA due to hepatic preneoplasia was
      decreased by the extract of BR, thus the pathological changes of tissues and
      cells can be reduced. CONCLUSION: BR extract has antioxidative effect which may
      be a part of the antitumor mechanism of B. rossica.

PMID- 12205986
TI  - [Effect of gui xin tong on sorbitol and nerve conduction velocity in diabetic
      rats].
AB  - OBJECTIVE: To investigate the effect of Gui Xin Tong(GXT) on sorbitol and nerve
      conduction velocity in diabetic rats. METHOD: The model rats suffering from
      diabetes were induced by STZ, and blood sugar levels above 16 mmol/L were chosen
      for observation. The rats were divided into GXT group, AG group and control
      group. The nerve conduction velocity, aldose reductase activity and sorbitol in
      STZ induced diabetic rats were investigated. RESULT: Compared with the control
      group GXT could increase the sciatic nerve conduction velocity significantly (P <
      0.05), decrease the RBC and sciatic nerve, aldose reductase activity, and RBC
      sorbitol content. CONCLUSION: GXT has the effect of improving nerve conduction
      velocity significantly and reducing aldose reductase activity and sorbitol

PMID- 12205987
TI  - [Effects and mechanism of thrombin on the expression of tissue factor activity in
      cultured bovine aortic endothelial cells].
AB  - OBJECTIVE: To explore the effects and mechanism of thrombin on the expression of
      tissue factor (TF) activity in cultured bovine aortic endothelial cells(BAECs).
      METHODS: BAECs were cultured according to Schwartz's method, and one stage
      clotting time assay was used to measure TF activity. RESULTS: 1. Thrombin
      enhanced the expression of TF activity in cultured BAECs. 2. A23187, a calcium
      ionophore, induced slightly the expression of TF activity, but markedly promoted
      the thrombin-induced TF activity in BAECs(P < 0.05). 3. TFP, a Ca2+/CaM
      inhibitor, inhibited the inductive effects of thrombin. 4. Pentoxifylline, a
      phosphodiesterase inhibitor, inhibited thrombin-induced TF activity in BAECs.
      CONCLUSION: Thrombin can induce the expression of TF activity in cultured BAECs,
      and the processes of signal transduction may be associated with Ca2+/CaM
      dependent pathway and cAMP.

PMID- 12205989
TI  - The role of cellular trace elements in oral carcinogenesis induced by 4
      nitroquinoline 1-oxide(4NQO).
AB  - The aim of this study was to define the changes of cellular trace element
      concentration during the carcinogenesis process of Wistar rat palatine mucosa
      squamous epithelial cell induced by 4-nitroquinoline-1-oxide (4NQO). 4NQO was
      painted three times weekly for nineteen weeks on the palatine mucosae of 28
      Wistar rats. Histologically normal, precancerous and squamous epithelial cell
      carcinoma tissues were obtained, and were studied by electron probe X-ray
      microanalysis. The measured elements were copper (Cu), zinc (Zn), selenium (Se),
      and molybdenum (Mo). The results were that both copper and zinc in the cellular
      nucleus and cytoplasm of the squamous epithelial carcinoma cells were
      significantly decreased. The concentration of cytoplasmic molybdenum
      significantly decreased in precancerous cells and significantly increased in
      squamous epithelial carcinoma cells. Minor changes in the concentration of
      selenium were observed in the process of normal to precancerous and then to
      cancerous cells. Cu/Zn increased in squamous epithelial carcinoma cells and Cu/Se
      and Zn/Se decreased in squamous epithelial carcinoma cells. These results suggest
      that the changes in intracellular copper, zinc, molybdenum are distinctly related
      to experimental oral carcinogenesis.

PMID- 12205988
TI  - [Study of monoclonal anti-idiotype antibody that bears the internal image of
      nasopharyngeal carcinoma associated antigen].
AB  - We prepared anti-idiotypic monoclonal antibodies (Ab2) against FC2 and HNL5 that
      recognized as nasopharyngeal cancer (NPC) associated antigens. These Ab2, which
      designated as 2H4 and 5D3, could inhibit the binding of FC2 or HNL5 to NPC cell
      lines. The anti-sera from the immunized mice that contained anti-anti-idiotype
      antibodies (Ab3) could compete with FC2 or HNL5 for binding with NPC cell by a
      competitive inhibition assay. When 2H4 or 5D3 immunized mice coupled with keyhole
      limpet hemocyanin(KLH), positive and specific delayed-type hypersensitivity (DTH)
      reaction occurred after the mice were stimulated by NPC cells. The proliferative
      response of the splenocytes was significantly higher in experimental groups than
      that in control groups. Therefore, it is suggested that the anti-idiotypic
      antibodies (Ab2) 2H4 and 5D3 are the Ab2 beta bearing the internal image of the
      epitope of NPC associated antigen, that either 2H4 or 5D3 expressing three
      dimensional shapes which resemble the structure of natural antigens can induce
      humoral and cellular immune response.

PMID- 12205990
TI  - [Candida albicans resistance and genotyping by randomly amplified polymorphic DNA
      method].
AB  - The Etest was used to determine the minimum inhibitory concentrations(MICs) of
      five antifungal agents for 30 C. albicans clinical isolates. Randomly amplified
      polymorphic DNA(RAPD) analysis was established and was used to type 30
      epidemiological unrelated strains of C. albicans. The relationship between
      genotype of C. albicans and its resistance to antifungal was analysed by
      dendrogram according to RAPD patterns. The results were that there were 2 of 30
      isolates of C. albicans against fluconazole and their RAPD profiles had high
      similarity. These results suggest that a high degree of genetic correlation
      exists between fluconazole-resistant patterns and RAPD profiles of C. albicans.

PMID- 12205991
TI  - [Abnormal expression of the FHIT gene in human primary gastrointestinal cancers].
AB  - OBJECTIVE: To evaluate the relationship between FHIT gene and gastrointestinal
      cancers. METHODS: Matched normal and cancerous tissues from 26 patients with
      primary gastric carcinoma and 30 patients with colorectal carcinoma were analysed
      by nested polymerase chain reaction(RT-PCR) and direct sequencing of the
      products. RESULTS: Seven of 26(26.9%) gastric cancer tissues and eight of
      30(26.7%) colorectal cancer tissues expressed aberrant FHIT transcripts, but no
      aberrant FHIT transcript was observed in all the matched normal tissues. Sequence
      analysis of the aberrant transcripts of 2 gastric cancer tissues(G8T, G25T) and 2
      colorectal cancer tissues(C5T, C26T) confirmed the absence of 1 to 3 exons of
      FHIT gene. CONCLUSIONS: The expression of aberrant FHIT transcripts is common and
      tumor-specific in gastrointestinal cancers and abnormalities of FHIT gene may be
      associated with gastrointestinal tumorigenesis.

PMID- 12205992
TI  - [Experimental study on immunization of mice with nucleic acid vaccine Sj31BIN
      combining IL-12 against Schistosoma japonicum].
AB  - Based on the anti-fecundity effect of Schistosoma japonicum nucleic acid vaccine
      Sj31BIN, we combined Sj31BIN with IL-12 in vaccination of mice to explore the
      role of IL-12 as an adjuvant. The result showed that immunization of the mice
      with Sj31BIN + IL-12 led to a significant decrease in adult worm recovery, a
      liver egg count reduction of 59.74%, an intestine egg count reduction of 59.60%
      and a liver surface egg granuloma reduction of 71.3%. In addition, vaccination of
      the mice with IL-12 alone also led to some but not significant decrease in adult
      worm recovery and the egg counts. It is concluded that Sj31BIN plus IL-12 induces
      significant anti-fecundity immunity.

PMID- 12205993
TI  - [Clinical significance and relation between ascendant velocity of artery systolic
      pressure and blood pressure].

PMID- 12205994
TI  - [A molecular epidemiologic study of TT virus in various population].
AB  - To investigate infection and sequence divergence of TT virus in various
      population, a nested polymerase chain reaction (nPCR) assay with primers from TTV
      ORF1 genome was used to detect serum TTV DNA. TTV DNAs from various population
      were cloned and sequenced. Six gene sequences derived from two patients with non
      A through non-E and non-G hepatitis, a hepatitis patient with HBsAg, a normal
      blood donor, an intravenous drug user and a woman prostitute, were compared with
      known sequence of TTV isolate (N22) reported by Okamoto, Japan. The nucleotide
      homology were 96%-98% and the whole sequences belonged to la genotype. The data
      indicate that TTV DNA from various population in China might chiefly be la
      genotype. There is no correlation between genotype and disease transmission and
      development.

PMID- 12205995
TI  - [The study on serological epidemiology of Helicobacter pylori infection in
      medical staffs].
AB  - Serum anti- Helicobacter pylori (Hp) IgG was determined using ELISA in 633
      medical staffs and 85 non-medical staffs(as controls) in order to know the
      prevalence of Hp infection. The results showed that Hp infection rate in medical
      staffs was significantly higher than that in non-medical staffs(P < 0.05). Among
      the medical staffs, the highest prevalence of Hp infection was found in
      gastroenterologists and dental doctors(P < 0.05). Also, Hp infection was
      significantly higher in subjects with dyspeptic symptoms than those without(P <
      0.01). It is concluded that medical staffs, especially gastroenterologists and
      dental doctors, have occupational risk for Hp infection.

PMID- 12205996
TI  - [A further research on physiopathological basis of "Liver Yang Forming Wind
      Syndrome"].
AB  - The multiple experimental parameters of different aspects in this study were
      determined in the patients with "Liver Yang Forming Wind Syndrome (LYFWS)", "Qi
      Deficiency Blood Stagnation Syndrome (QDBSS)" and "Yin Deficiency Forming Wind
      Syndrome (YDFWS)". The results showed that cerebral hemorrhage was similar to
      cerebral infarction in almost all parameters and the two diseases were with
      LYFWS. It was found that there were several characteristics in LYFWS, i.e. 1.
      Hyperfunction of sympathetic adrenal medullary system. 2.
      Hypotriiodothyroidoglobulin syndrome. 3. The marked changes of the active
      substance regulating vessel smooth muscle function. 4. The increased inflammatory
      medicators. The pathophysiological parameters in patients with QDBSS were the
      same as those with YDFWS, but the changes of QDBSS and YDFWS weRe milder than
      those of LYFWS.

PMID- 12205997
TI  - [The effect of increasing ventral movement on the small solutes transport during
      peritoneal dialysis].
AB  - OBJECTIVE: To investigate whether the small solutes transport and the efficiency
      of peritoneal dialysis can be improved through ventral movement. METHODS:
      Eighteen continuous ambulatory peritoneal dialysis (CAPD) patients and 6 male New
      Zealand rabbits peritoneal dialysis models were observed. Through self and pre
      post control, we compared the concentration ratio of the solutes in effluent
      dialyste(D) to the solutes in plasma(P), mass transfer area coefficient and the
      drained volume. RESULTS: The animal experiments showed that the D/P value for BUN
      was different prominently when comparing the vibration and non-vibration groups
      in 45 min and 60 min separately(P < 0.05). On the contrary, no obvious difference
      existed between the two groups when comparing the D/P values for protein and
      drained volume. The clinical study showed: D/P value for BUN at the 2 and 4 hr
      and D/P value for creatinine at the 2 hr increased obviously either in the low or
      high frequency group when compared with the control group(P < 0.01, P < 0.01, P <
      0.05, respectively). D/P for protein and drained volume had no difference
      compared with the control group(P > 0.05). CONCLUSION: The ventral movement and
      vibration could efficiently increase the transport of small solutes such as BUN
      and creatinine while had no influence on the transport of large molecular solutes
      such as protein and the ultrafiltration volume. It suggested that increasing the
      movement of CAPD patients can improve the efficiency of peritoneal dialysis.

PMID- 12205998
TI  - [Analgesic effect of tramadol in the treatment of pulpitis].

PMID- 12205999
TI  - [Protective effect of ischemic preconditioning on ischemia-reperfusion injury].
AB  - OBJECTIVE: To study the protective effect of ischemic preconditioning(IP) on
      ischemia-reperfusion injury of limb. METHODS: One to three times of short-term
      ischemia was applicated before prolonged ischemia, a series of biological
      examinations, including creatine phosphate kinase(CPK), glutamic-oxalacetic
      transaminase(GOT), lactic dehydrogenase(LDH), malondiadehyde(MDA) and superoxide
      dismutase(SOD) were carried out in each group. RESULTS: Compared with the
      control, release of skeletal muscle intracellular enzyme(CPK, GOT and LDH)
      decreased in experiment groups after preconditioning had been performed. The
      serum concentration of MDA was lower, activity of SOD was higher, and
      pathological lesion was less in preconditioning groups than that in non
      preconditioning group. Different frequency of preconditioning led to different
      results. CONCLUSIONS: Preconditioning has protective effect on ischemia
      reperfusion injury of limbs, and the effect of IP is correlated with the number
      of preconditioning cycles.

PMID- 12206000
TI  - [Role of nitric oxide in pathogenesis of pregnancy induced hypertension].
AB  - OBJECTIVE: We attempted to investigate the role of nitric oxide(NO) in
      pathogenesis of pregnancy-induced hypertension(PIH). METHODS: No-nitro-L-arginine
      methyl ester(L-NAME) was used to inhibit nitric oxide synthase(NOS) in pregnant
      rats. Indices including blood pressure, urine protein concentration, pup weight,
      serum NO level and plasma ET-1 level were measured. Nitroglycerin, a nitric oxide
      donor, was used to observe its impact on the effect of L-NAME at the same time.
      RESULTS: Infusion of L-NAME elevated blood pressure, increased urine protein
      concentration, decreased pup weight, decreased serum NO level and raised plasma
      ET-1 level(P < 0.01, respectively); However in the L-NAME-treated animals
      nitroglycerin significantly lowered blood pressure, decreased urine protein
      concentration, increased pup weight, increased serum NO level and decreased
      plasma ET-1 level(P < 0.01, respectively). CONCLUSIONS: 1. Infusion of L-NAME, an
      inhibitor of NOS, causes decreased serum NO level and some signs similar to
      preeclampsia such as hypertension, proteinuria and intrauterine growth
      retardation(IUGR). Nitroglycerin can reverse the lesions induced by the treatment
      of L-NAME. These findings indicate that reduced level of NO may be a factor
      responsible for PIH. 2. NO can decrease the plasma ET-1 level. NO may regulate
      the process of PIH via ET-1 pathway. It may be one mechanism for NO. 3. An useful
      animal model for PIH is provided to test novel therapeutic and preventive
      strategies.

PMID- 12206001
TI  - [Effects of nitroprusside and vibration on peritoneal transport of solutes in
      continuous ambulatory peritoneal dialysis patients].
AB  - To explore the relationship between peritoneal transport of solutes and
      permeability of the peritoneum capillary as well as peritoneal stagnant fluid
      layer within dwell time, we observed the effects of nitroprusside and vibration
      on peritoneal transport of solutes in continuous ambulatory peritoneal
      dialysis(CAPD) patients. Twelve stable, routine CAPD patients were involved, who
      had no peritonitis for at least 4 weeks before the test. Standard peritoneal
      equilibrium tests(PETs) were performed, and mass transfer area coefficiency(MTAC)
      were calculated after adding nitroprusside to the dialysate or vibrating the
      patients's peritoneum. The concentrations of total protein, albumin and immunity
      globulin G in total drained dialysate were examined, and total drained volumes
      were recorded. Compared with the control, the MTACs value of BUN, Creatinine(Cr)
      increased significantly both in the nitroprusside group and vibration group(P <
      0.05); the concentration of immunoglobin G in the total drained fluid was higher
      in the nitroprusside group than that in the control(P < 0.05); However, there was
      no significant difference in the total drained volume among the three groups. We
      conclude that nitroprusside and vibration can increase the peritoneal transport
      of small molecular solutes, and vibration has less influence on the loss of
      protein in CAPD. It suggests that moderated movement may improve the removal of
      the small molecules in CAPD patients.

PMID- 12206002
TI  - [Effect of pantoprazole on non-variceal bleeding].
AB  - The treatment effect of 101 non-variceal bleeding(NVB) patients treated with
      pantoprazole was observed, and it was compared with 57 NVB patients treated with
      omeprazole. RESULTS: 87.1% of the patients in 48 h and 97% of the patients in 72
      h with Pantoprazole bleeding-stopped. And the result was almost equal to
      omeprazole group. The side-effect of pantoprazole was few and slight. It is
      suggested that pantoprazole is effective and safe on treating NVB.

PMID- 12206003
TI  - [Effects of nitroglycerin and dexamethasone on nitric oxide and endothelin
      derived from alveolar macrophages in patients with mild and middle asthma].
AB  - OBJECTIVE: To investigate the changes about nitric oxide(NO), endothelin(ET)
      derived from alveolar macrophages(AMs) and the effects of nitroglycerin(NTG) and
      mexamethason(DXM) on ET and NO in patients with mild and middle asthma. METHODS:
      The AMs from 7 healthy control subjects and 15 patients with attacking asthma
      were purified, and divided into healthy control unpretreated(Group 1), asthmatic
      unpretreated (Group 2), asthmatic pretreated by DXM(Group 3), asthmatic
      pretreated by NTG(Group 4). All purified AMs were cultured for 48 hours. The NO
      level and ET level in supernatant and the expression of iNOS-mRNA, ET-mRNA of
      cultured AM from above subjects were examined by copper coated cadmiunm
      reduction, radioimmunoassay method and in situ hybridization respectively.
      RESULTS: 1. The AM of Group 1 secreted a little of NO, ET and expressed a little
      of iNOS-mRNA and ET-mRNA; 2. The NO and ET level in supernatant and the
      expression of iNOS-mRNA and ET-mRNAin Group 2 were evidently higher than those in
      other groups(P < 0.05, respectively); 3. The NO and ET level in supernatant and
      the expression of iNOS-mRNA and ET-mRNA in Group 3 were evidently decreased, but
      they were still higher than those in Group 1(P < 0.05, respectively); 4. The NO
      level in Group 4 was higher than that in other groups(P < 0.05, respectively); 5.
      The expression of iNOS-mRNA was negatively correlated with the NO level(r = 
      0.59, P < 0.05), and the expression of ET-mRNA was positively correlated with the
      ET level(r = 0.92, P < 0.01) in Group 4. CONCLUSION: The AMs from patients with
      asthma exacerbation secrete a large quantity of NO and ET because of the
      increasing expression of iNOS-mRNA, ET-mRNA; DXM can inhibit the expression of
      iNOS-mRNA and ET-mRNA, and decrease NO and ET level, but the NO and ET level are
      still abnormal; NTG can improve directly the production of NO and inhibit
      significantly the expression of iNOS-mRNA and ET-mRNA as well as decrease the ET
      level.

PMID- 12206005
TI  - [The technical improvement of staining of trichomonas vaginalis].

PMID- 12206004
TI  - [A study of the autoimmune pathogenesis of chronic HCV infection].
AB  - To explore the autoimmune pathogenesis of chronic hepatitis C virus(HCV)
      infection. Anti-GOR, antinuclear antibodies(ANA), thyroglobulin antibody(TGA),
      thyroid microsome antibody(TMA), serum levels of soluble Fas(sFas), and
      peripheral blood lymphocyte(PBMC) subsets and their apoptosis were measured in
      chronic HCV infection by using immunity assay and flow cytometry, respectively.
      The results showed that the positive rates of anti-GOR, ANA and TMA/TGA were
      significantly higher in chronic HCV-infected patients than those in normal
      controls(P < 0.01, respectively). In comparison with chronic HBV infected
      patients, anti-GOR and ANA were also significantly increased in chronic HCV
      infected patients(P < 0.01, P < 0.05, respectively). The serum levels of sFas
      were significantly higher in chronic HCV infection than those in healthy donors(P
      < 0.01). The apoptosis percentage of PBMCs and CD3+ cell was all increased in
      chronic HCV infection (vs normal controls P < 0.05). However, the apoptosis
      percentages of CD4+ T and CD19+ B cells in PBMCs were significantly decreased in
      patients with anti-GOR positive as compared with anti-GOR negative(P < 0.01, P <
      0.05). The results indicate that autoimmune reactions and the imbalance of
      lymphocyte apoptosis exist during chronic HCV infection. Decreasing of the
      apoptosis of CD4+ T and CD19+ B lymphocytes may be the important reasons for the
      mechanism of autoimmune pathogenesis of chronic HCV infection. Increased serum
      levels of sFas may be responsible for the decrease of the apoptosis in a part of
      lymphocytes in chronic HCV infection.

PMID- 12206006
TI  - [Effect of human serum on the growth of Helicobacter pylori].
AB  - To investigate whether sheep blood could be replaced with human serum or fetal
      calf serum for Helicobacter pylori(Hp) culture, Hp was inoculated onto the
      culture plates containing 7% of sheep blood, human serum, or fetal calf serum
      respectively. The colonies were counted after 5 days of culture. Similar culture
      results were obtained in the plates containing sheep blood, human serum, or fetal
      calf serum respectively. No effect of anti-Hp-IgG antibody in human serum on the
      growth of Hp was found (P > 0.05). However, heat-inactivated human serum
      significantly suppressed the growth of Hp (P < 0.01). Human serum or fetal calf
      serum may be used for Hp culture where sheep blood is not available. Bactericidal
      activity against Hp in human serum is mediated by complements.

PMID- 12206007
TI  - [Discriminant function based on serum analyte for diagnosis of primary hepatic
      cancer].
AB  - OBJECTIVE: The aim of this study was to diagnose primary hepatic cancer(PHC).
      METHODS: Seven serum indexes of 92 serum samples consisting of 48 controls and 44
      PHC were detected. Four discriminant functions based on seven serum indexes were
      obtained with computer SPSS statistic package. RESULTS: The rate of coincidence,
      sensitivity, and specificity of the general discriminant functions were 86.96%,
      77.27%, and 95.83% respectively; and that of the stepwise discriminant functions
      were 84.78%, 79.55%, and 89.59% respectively. CONCLUSION: Usually PHC can be
      diagnosed by analyzing patients serum indexes with the discriminant functions.

PMID- 12206008
TI  - [Effect of Panax notoginseng saponins combined isovolumic haemodilution on the
      retinal microcirculation of patients with retinal vein occlusion].
AB  - OBJECTIVE: To study the effect of Panax notoginseng saponins (PNS) or isovolumic
      haemodilution (IHD) and combination of PNS with IHD on retinal microcirculation
      of patients with retinal vein occlusion (RVO). METHOD: Seventy three patients
      with RVO were allocated at random to three groups which were treated with PNS,
      IHD, or PNS + IHD respectively. The retinal circulation time (RCT) and retinal
      hemorrhage, edema, leakage of capillary, cystoid macular edema (CME), and
      nonperfusion area of capillary in retina were observed before and after
      treatment. RESULT: RCT of patients with RVO was shortened by three treating
      methods. RCT in the patients who treated by PNS + IHD was the shortest,
      especially in the patients with nonischemic RVO and branch retinal vein
      occlusion(BRVO). The retinal hemorrhage, edema, leakage of capillary, and CME in
      the patients treated by PNS + IHD disappeared quicker than those treated by PNS
      or IHD. At the same time, the incidence of nonperfusion area in patients whose
      course of disease was shorter than fourteen days was decreased. The perfusion of
      capillaries was increased at the edge of nonperfusion area which existed before
      the treatment. But the effect for nonperfusion area which existed before the
      treatment in the type of ischemic RVO was not obvious. CONCLUSION: The treatment
      of PNS + IHD can both shorten RCT of patients with RVO, and promote absorption of
      retinal hemorrhage, edema, leakage of capillary, and CME. It is possible that PNS
      + IHD treatment also has an effect to decrease the forming of nonperfusion area
      in patients whose course of disease is at early stage.

PMID- 12206009
TI  - [Heat shock protein 70 expression following transient ischemia in the gerbil].
AB  - OBJECTIVE: To study the expression of heat shock protein 70(HSP70) following
      transient ischemia in the gerbil. METHODS: Immunohistochemistry(IHC) was used to
      determine the expression of the HSP70 protein in the forebrain during different
      periods after post-ischemic reperfusion in the gerbil, and the neuronal damage
      was examined with microscope. RESULTS: The HSP70 protein was only expressed at
      the 1st day of reperfusion(P < 0.01); and most of the neurons showed damage on
      the 7th day of reperfusion; heat-preconditioning could increase the expression of
      HSP70 protein(P < 0.01) and decrease the neuronal damage(P < 0.001) after 6 min
      of ischemia. CONCLUSION: Heat-preconditioning could protect neural cells from
      damage by increasing the expression of the HSP70 protein.

PMID- 12206010
TI  - [Effects of urapidil on cardiovascular response to tracheal intubation and
      incision during fentanyl co-induction].
AB  - To study the effects of urapidil (URA) on cardiovascular response to tracheal
      intubation and incision during fentanyl co-induction, forty-two patients (ASA I
      II) were randomly divided into four groups: Group F1(n = 10), fentanyl 5
      micrograms.kg-1 was given by venous injection; Group F2(n = 10), fentanyl 10
      micrograms.kg-1; Group U1(n = 10), URA 0.25 mg.kg-1 plus fentanyl 5 micrograms.kg
      1; Group U2(n = 12), URA 0.5 mg.kg-1 plus fentanyl 5 micrograms.kg-1. After
      tracheal intubation, mean arterial pressure (MAP), diastolic pressure (DP) in
      Group F1 and systolic pressure (SP) in Group U1 were increased more significantly
      than those in Group U2(P < 0.05). After incision, the values of SP, MAP, DP and
      rate-pressure product (RPP) in Group F1 were higher apparently than those in
      Group U2(P < 0.05); at the 5th minute, SP, MAP, heart rate (HR) and RPP in Group
      F1 were in higher than those in Group F2 (P < 0.05), and SP, MAP in Group U2 were
      lower than those in Group U1(P < 0.05). It is suggested that the cardiovascular
      response to tracheal intubation and incision may be effectively inhibited in
      combination URA with fentanyl, and the dosage of fentanyl might reduce.

PMID- 12206011
TI  - [The protection of renal function in the ACEI treatment of renal hypertension].
AB  - OBJECTIVE: To explore the influence of angiotensin-converting enzyme inhibitors
      (ACEI) on plasma endothelin (ET-1), nitric oxide (NO) and renal function in renal
      hypertension patients. METHODS: Sixty renal-hypertension patients (Group II) were
      treated with ACEI (lotensin) for 10 weeks then we measure their blood pressure
      (BP), plasma ET-1, NO and renal functions (BUN, Scr and proteinuria) before and
      after the treatment. Thirty healthy persons (Group I) acted as control. RESULTS:
      The level of plasma ET-1 was higher and plasma NO was lower in Group II than
      those in Group I. After the treatment of ACEI plasma ET-1 and proteinuria were
      decreased (P < 0.01), and NO increased in Group II significantly (P < 0.01),
      while BUN and Scr decreased in abnormal-renal function patients (Group II2) (P <
      0.05, P < 0.01). CONCLUSION: The Study indicates that: ACEI is effective to renal
      hypertension; it decreases plasma ET-1 and increases NO in the renal hypertension
      patients; ACEI may play an important role in protection of renal functions and
      prolonging the chronic renal failure.

PMID- 12206012
TI  - [Clinical study on nosocomial infection in patients with burns].
AB  - OBJECTIVE: To study clinical characters and related factors of nosocomial
      infection in patients with burns. METHODS: To study 782 cases of burns as a group
      hospitalized in our department for more than 48 h, from January, 1993 to
      December, 1996. Prospective and retrospective investigation of infection
      locations, infection rates, pathogen and drug sensibility was carried out.
      RESULTS: The infection most often found in blood and wound, less often in
      respiratory system. Nosocomial infection rates in patients with burns were
      closely related to the severe degree, diagnosis and therapy of these patients and
      hospital surroundings. Infection bacteria species: Gram-positive bacterium
      accounted for 43.82%, and mainly were staphylococcus aureus and anaerobic
      peptococcus. Gram-negative bacterium accounted for 52.81%, of which pseudomonas
      aeruginosa and nitrate-negative bacillus constituted the majority. CONCLUSION:
      According to these characters and related factors of nosocomial infection in
      patients with burns, effective measures of preventing and controlling infection
      should be taken, so that the incidence of nosocomial infection in these patients
      will drop.

PMID- 12206013
TI  - [Evaluation of two-dimensional and color Doppler ultrasonography in diagnosis of
      peritoneal mesothelioma].
AB  - OBJECTIVE: To evaluate diagnostic value of two-dimensional and color Doppler
      ultrasonography in peritoneal mesothelioma. METHODS: Ten cases of ultrasonograms
      and color Doppler ultrasonographic manifestations in 3 cases of them were
      analysed and compared with the outcome of surgery and pathology. RESULTS: Images
      of 8 cases were showed to be hypoechoic mass which some had no-echoic area; 5 to
      be ascites; 5 to be peritoneal thickness. With color Doppler, we saw the mass
      which is rich in the blood flow. CONCLUSION: Combining clinical manifestations,
      ultrasonography is of benefit to initial diagnosis of peritoneal mesothelioma.

PMID- 12206014
TI  - [The expression of p16 and Rb protein in the tissue of cervical squamous
      carcinoma].
AB  - OBJECTIVE: To study the aberrant expression and coexpression of protein p16 and
      Rb in cervical squamous carcinomas, and to evaluate whether these alterations
      provide causative information. METHODS: The expressions of p16 and Rb protein
      were detected by treptavidin-peroxidase(S-P) immunohistochemical methods.
      RESULTS: 1. The p16 protein expression was mainly found in cytoplasm. The
      positive rate in carcinoma, CIN and normal cervix were 43.1%(25/58), 62.5%(5/8)
      and 70%(14/20), respectively; the positive expression were decreased in lower
      grade and clinical advanced cases(P < 0.05). 2. The Rb protein expression was
      detected in nucleus. The positive rate of Rb protein were 37.9%(22/58), 75%(6/8)
      and 85(17/20) in tum. The difference of the expression of Rb protein between the
      cervical squamous carcinoma and the normal cervix was significant(P < 0.05). The
      positive expression were increased in lower grade cancers(P < 0.05), and
      decreased in advanced cases(P > 0.05). 3. The positive rates of p16 and Rb
      protein in cervical squamous carcinoma showed an inverse correlation (vs = 
      0.4301, P < 0.01). CONCLUSIONS: 1. The abnormal p16 and Rbn expression might play
      an important role in the tumor genesis and the development of cervical squamous
      carcinoma. 2. Loss of function of both tumor suppressor genes may be an advanced
      event in cervical squamous carcinomas and might involve a bad prognosis.

PMID- 12206015
TI  - [Expression of bcl-2 in acute leukemia patients and its significance].
AB  - RT-PCR method was used to detect the expression level of bcl-2 gene in 38
      patients of acute leukemia. RESULTS: Expression level of bcl-2 in the patients
      with clinical refractoriness increased more obviously than previously untreated
      and CR patients, and the expression level of bcl-2 was obviously correlated with
      clinical refractoriness(r = 0.83, P < 0.01), which indicated that high expression
      of bcl-2 was one of the factors in clinical refractoriness. It was also a
      sensitive method for predicting the effect of anti-tumor agents and prognosis in
      clinic work.

PMID- 12206016
TI  - [Ischemic preconditioning decrease the release of cardiac troponin T during heart
      valve replacement].
AB  - Using cardiac troponin T(cTnT), a highly sensitive and specific marker of
      myocardial injury, we evaluated the effects of ischemic precondition on ischemic
      reperfusion myocardial injury. Thirty two patients were randomly divided into
      control group(n = 16) and ischemic preconditioning group(n = 16). The marker cTnT
      was measured in each group before operation, and 4 h, 24 h and 72 h after
      operation. The results showed that the peak value of cTnT was lower, and more
      quickly recovered in the preconditioning group than that in the control. It is
      suggested that ischemic preconditioning exert an evidently protective effect on
      ischemic reperfusion myocardial injury.

PMID- 12206017
TI  - [Levels of plasma TF and TFPI activities in patients with acute leukemia].
AB  - OBJECTIVE: To investigate the changes of plasma tissue factor(TF) and tissue
      factor pathway inhibitor(TFPI) activities in the patients with acute leukemia.
      METHODS: TF and TFPI activities were measured by using chromogenic assays.
      RESULTS: Plasma TF activity in the patients with acute leukemia was higher and
      TFPI activity was lower than those in normal(P < 0.01). In 7 patients who
      underwent the first chemotherapy, the plasma TF activity was decreased after
      chemotherapy(P < 0.01), while TFPI activity increased(P < 0.05). CONCLUSION: The
      unbalance between plasma TF and TFPI activities contributes to the coagulant
      disorders in acute leukemia.

PMID- 12206018
TI  - [A quantitative analysis of renal pathology in the children with anaphylactoid
      purpura nephritis (APN)].
AB  - OBJECTIVE: To provide the theoretical value for the treatment and prognostic
      judgement of APN. METHODS: All cases were scored on the pathologic change of
      glomeruli and tubules. RESULTS: The pathologic scores of glomeruli in 30 cases
      were as follows: no one on Grade 0; 6(20%) on Grade 1; 17(56.7%) on Grade 2 and 7
      (23.3%) on Grade 3. The pathologic scores of tubule were: Grade 0 was 2(6.7%);
      Grade 1 was 6(20%); Grade 2 was 14(46.7%); Grade 3 was 8(26.7%). There was
      positive correlation between glomerulus and tubule pathologic degree(r = 0.783, P
      < 0.01). The pathologic score of nephrotic syndrome in clinical manifestation was
      higher than that of non-nephrotic syndrome(P < 0.01). There was no significant
      difference in glomerular pathologic score between the simple urinary protein
      group and acute glomerulonephritis(AGN) group(P > 0.05), but tubular pathologic
      score in simple urinary proteins group was higher than that of AGN and essential
      hematuria group (P < 0.01, P < 0.05). The pathologic score of kidney(including
      glomerulus and tubule) was positively correlated with the disease course(r =
      0.563, P < 0.01), but not with serum urea nitrogen and creatinine(r = 0.281, r =
      0.236, P > 0.05). CONCLUSION: Serious tubular pathologic changes(not only
      glomerular pathologic change, but also tubular pathologic change in the APN
      children) were found in the patients with nephrotic syndrome and simple urinary
      proteins. Long-term urinary protein and the recurrence of the disease may be the
      important risk factor in kidney pathologic of APN.

PMID- 12206020
TI  - [Determination of tetrandrine in human plasma by high-performance liquid
      chromatography].
AB  - The paper reports the determination of tetrandrine by high performance liquid
      chromatography (HPLC). A C18 column was used and the mobile phase was methanol
      water(80:20) containing 0.03% triethylamine, detective wave was at 282 nm, the
      internal standard was diazepam, the sample was extracted with ether. The linear
      range was from 0.289 microgram.ml-1 to 4.618 micrograms.ml-1, the average
      recovery rate was 95.8%. The coefficients of variation of within-day and day-to
      day were less than 5%. This method is simple, rapid and accurate. It can be used
      in biomedical sample analysis of tetrandrine.

PMID- 12206019
TI  - [The expression and significance of VEGF mRNA and bFGF mRNA in the malignant
      neoplasms of ovary].
AB  - The expression and significance of VEGF mRNA and bFGF mRNA in the malignant
      neoplasms of ovary were studied by in situ hybridization technique. The results
      were that the positive rates of VEGF mRNA and bFGF mRNA were higher in the serous
      adenocarcinoma and embryonal carcinoma than that in the mucous adenocarcinoma and
      granulosa cell tumor. The positive rates of VEGF mRNA and bFGF mRNA were lower in
      the cases of clinical Stage I and without metastasis than that of clinical Stage
      III-IV and with metastasis. The results suggest that the expressions of VEGF mRNA
      and bFGF mRNA might be related to the pathological types, clinical stages, and
      metastasis of the malignant neoplasms of ovary and the patients who have positive
      expression of VEGF mRNA and bFGF mRNA might have a poor prognosis.

PMID- 12206021
TI  - [Filling blood vessels with latex and its application].
AB  - The purpose of this study is to find out the better conditions for filling blood
      vessels of the body with latex. We test it on 500 bodies. Our data show that the
      temperature for storing the latex, filling positions, the wash of blood vessels
      prior to filling and filling pressure are all important in this process. A good
      filling increases elasticity of vessels, makes vessels stronger and facilitates
      dissection of vessel. It is of importance in the study of cardiovascular system.

PMID- 12206022
TI  - [Approach to application of laser scanning confocal microscope in bone
      morphometry].
AB  - The laser scanning confocal microscope(LSCM) is the new high distinguishing
      microscope, which can be used in observation on fluorescence, since 1990. The
      bone morphometry is an important way to study metabolic bone diseases. Our study
      on research combination of LSCM with bone morphometry in observing
      microarchitecture of bone found that LSCM could make the photo of bone trabecula
      distinctly and its location accurately. Because of its technical advantages, LSCM
      could link histochemical or immunohistochemical method for the bone morphometry
      and bone cells at the same time and obserrate the thick-slide. It is a new method
      and way to study and diagnose metabolic bone diseases.

PMID- 12206023
TI  - [Significance of preoperative digital subtraction dacryocystography for
      nasolacrimal stent].
AB  - Digital subtraction dacryocystography were performed prior to placement of a
      nasolacrimal stent. Among the 107 eyes, the sites of obstruction were in the
      common canaliculus in 9 eyes, above the neck of the lacrimal sac in 12 eyes and
      under the neck of the lacrimal sac in 86 eyes. The placement of a nasolacrimal
      stent may become the treatment of choice for epiphora due to obstruction of the
      nasolacrimal duct at the saccular or subsaccular level. After operation, these
      nasolacrimal ducts after stenting were patent and epiphora was resolved
      completely or partially. The results suggest that the preoperative digital
      subtraction dacryocystography is helpful in selective indication of placement of
      a nasolacrimal stent and prognostic assessment of the postoperative outcome.

PMID- 12206024
TI  - [The state of hepatitis C virus in peripheral blood mononuclear cells of infected
      patients].

PMID- 12206025
TI  - [Relation between the position and parameter of the radio frequency delivery and
      acute myocardial injury].

PMID- 12206026
TI  - [Inhibitory effect of tumor necrosis factor and interferon with chemotherapeutic
      drugs on the growth of cancer cell of tongue].

PMID- 12206027
TI  - [Diagnosis of inner-lymphoma of extra-lung tuberculosis].

PMID- 12206028
TI  - [Effect of "home of asthma" action on patients with asthma].

PMID- 12206029
TI  - Clinical efficacy of an optimized stannous fluoride dentifrice, Part 2: A 6-month
      plaque/gingivitis clinical study, northeast USA.
AB  - The objective of this 6-month, double-blind clinical study, conducted following
      the American Dental Association guidelines, was to investigate the efficacy of
      Colgate Optimized Stannous Fluoride (COSF) dentifrice for the control of
      supragingival dental plaque and gingivitis. This dentifrice contains 0.454%
      stannous fluoride, stannous chloride, polyphosphate, and citrate in a silica
      base. At the 3- and 6-month study examinations, the COSF dentifrice group
      exhibited statistically significant reductions in both plaque and gingivitis
      compared to the control dentifrice group. At the 6-month examination, the
      magnitude of these percent reductions exceeded 20% for all 4 parameters measured.
      Thus, the results of this study support the conclusion that the COSF dentifrice
      is efficacious for the control of supragingival plaque and gingivitis.

PMID- 12206031
TI  - The scientific rationale and development of an optimized stannous fluoride
      dentifrice, Part 1.
AB  - Stannous fluoride has been recognized as an effective anticavity therapeutic
      agent since the early 1950s. There has recently been a resurgence in activity to
      discover ways to fully exploit its documented antimicrobial activity. Through the
      use of targeted in vitro methodology to predict in vivo efficacy, a highly
      optimized stannous fluoride dentifrice has been developed. Careful selection of
      stabilizing agents formulated into a unique system has resulted in a Colgate
      Optimized Stannous Fluoride (COSF) dentifrice that has been proven to
      simultaneously help control supragingival plaque, gingivitis, supragingival
      calculus, and caries. Furthermore, the COSF dentifrice has been clinically shown
      not to cause the traditional stannous fluoride staining of dentition.

PMID- 12206030
TI  - Clinical efficacy of an optimized stannous fluoride dentifrice, Part 3: A 6-month
      plaque/gingivitis clinical study, southeast USA.
AB  - This 6-month, double-blind clinical study, also following the American Dental
      Association guidelines, investigated the efficacy of Colgate Optimized Stannous
      Fluoride (COSF) dentifrice in controlling supragingival dental plaque and
      gingivitis. The same dentifrice, containing 0.454% stannous fluoride, stannous
      chloride, polyphosphate, and citrate in a silica base was used. Adult men and
      women from the Atlanta, Georgia, area received an oral prophylaxis and were
      instructed to brush their teeth twice daily (morning and evening) for 1 minute
      with their assigned dentifrice, using a soft-bristled toothbrush. As in the first
      study, plaque and gingivitis examinations were conducted after 3 months and again
      after 6 months of using the dentifrices. At both the 3- and 6-month study
      examinations, the COSF dentifrice group exhibited statistically significant
      reductions in both plaque and gingivitis compared to the control dentifrice
      group. At the 6-month examination, the magnitude of these percent reductions
      exceeded 20% for all 4 parameters measured. Thus, the results of this study
      reflect those found in the New Jersey study, i.e., supporting the conclusion that
      the COSF dentifrice is efficacious for the control of supragingival plaque and
      gingivitis.

PMID- 12206032
TI  - Clinical efficacy of an optimized stannous fluoride dentifrice, Part 4: A 3-month
      calculus clinical study, northwest USA.
AB  - The objective of this 3-month, double-blind study was to investigate the efficacy
      of Colgate Optimized Stannous Fluoride (COSF) dentifrice for the control of
      supragingival dental calculus accumulation. After 3 months' use, the COSF
      dentifrice group exhibited a statistically significant 56.6% reduction in
      supragingival calculus formation, as compared to the control dentifrice group.
      The results of this study support the conclusion that the COSF dentifrice is
      efficacious for controlling the accumulation of supragingival calculus.

PMID- 12206034
TI  - Evaluation of influenza virus detection by direct enzyme immunoassay (EIA) and
      conventional methods in asthmatic patients.
AB  - Throat gargle specimens of fifty-seven acute asthmatic patients (age range 18-40
      years) were collected for the study. Thirty-four patients were found influenza
      virus positive in acute asthma cases. Influenza virus was isolated by
      conventional culture method on MDCK cell-line and by enzyme immunoassay test
      (EIA). The EIA negative specimens were retested after virus amplification on MDCK
      cell-line. Virus shedding and virus surface receptors assay was carried out to
      determine influenza virus titre. Airway functions were measured by spirometry. A
      good relationship was observed between the degree of airflow limitation and
      presence of influenza virus infection (p < 0.001; r = 0.85). A comparable
      difference in % FEV1 was observed in relation to the symptoms. The patients with
      greater viral antigen load had lower % FEV1. Two specimens, which were EIA
      negative, turned out to be positive after amplification on MDCK cell-line. The
      sensitivity was 98% and specificity was 100%. It was concluded that EIA method is
      a useful diagnostic tool as it detects influenza viral antigen quickly as
      compared to conventional methods.

PMID- 12206033
TI  - Clinical efficacy of an optimized stannous fluoride dentifrice, Part 5: A 3-month
      study of extrinsic tooth staining, northeast USA.
AB  - The objective of this 3-month, double-blind clinical study was to investigate the
      level of tooth staining associated with the use of Colgate Optimized Stannous
      Fluoride (COSF) dentifrice compared to the tooth staining associated with two
      commercially available dentifrices. The results of this clinical study support
      the conclusion that the intensity and extent of extrinsic tooth stain associated
      with the use of the COSF dentifrice are significantly lower than that associated
      with Crest Gum Care Toothpaste. Further, this study provided no indication that
      the use of the COSF dentifrice is associated with a greater level of stain than
      that associated with the use of Crest Regular Toothpaste, a standard 0.243%
      sodium fluoride/silica dentifrice.

PMID- 12206035
TI  - Primary multi-drug resistant tuberculous gumma.
AB  - A 28-year old lady presented with three discrete gummatous lesions on the
      anterior abdominal wall, one at the site of a previous laparoscopic scar. Skin
      biopsy showed epitheloid cell granulomas and a pus culture and sensitivity (for
      AFB) performed, showed growth of M. tuberculosis. The culture-isolate was
      resistant to all the essential anti-TB drugs. The patient was put on second line
      anti-TB chemotherapy and the gummas resolved.

PMID- 12206036
TI  - Antigen distribution pattern of West Nile virus in Culex tritaeniorhynchus, Culex
      vishnui and Culex pseudovishnui mosquitoes.
AB  - Distribution of West Nile (WN) virus antigen in different tissues of mosquitoes
      was studied in three species viz., Culex tritaeniorhynchus, C. vishnui and C.
      pseudovishnui. Overall per cent positivity was higher in the intra thoracically
      inoculated as compared to the orally infected mosquitoes, suggesting the
      existence of a midgut barrier. In a small number of mosquitoes salivary glands
      were found negative even though fluorescence was seen in the respective head
      squashes, suggesting salivary gland barrier in these mosquitoes. There was no
      difference in the per cent salivary gland and salivary gland area positivity
      between these three species. Presence of virus antigen in the ovaries of these
      three species on the 3rd post infection day suggests the possibility of
      transovarial transmission of virus even in the first gonotrophic cycle, which is
      of epidemiological importance.

PMID- 12206037
TI  - Relative efficacy of DEPA and neem oil for repellent activity against Phlebotomus
      papatasi, the vector of leishmaniasis.
AB  - The insect repellent N, N-diethylphenyl acetamide (DEPA) was compared with neem
      oil, a commercial preparation, for protection against 3 day old un-fed female of
      the sandfly, Phlebotomus papatasi, (Diptera: Psychodidae) under laboratory
      conditions on mouse. The percentage protection against sandfly bite provided by
      neem oil was significantly higher than DEPA when applied at 1% and 2%
      concentrations (p = 0.000, t = 21.474; df = 6 and p = 0.001, t = 5.960; df = 6
      respectively). However, neem oil did not show any significant difference with
      DEPA at 5% (p = 0.1682, t = 0.15667; df = 6). This clearly indicates that at
      higher concentration (5%) both neem oil and DEPA exhibited similar repellent
      action against P. papatasi.

PMID- 12206038
TI  - Eye lesions and onchocerciasis in a rural farm settlement in Delta State,
      Nigeria.
AB  - Between December 1999 and September 2000, an investigation on 326 inhabitants who
      voluntarily participated in screening for eye lesions and onchocerciasis in a
      rural farm settlement in Aniocha North local government area of Delta State,
      Nigeria was carried out. Microfilariae were reported in the skin tissues of 134
      (41.1%) inhabitants. Of these, males had more microfiladermia (49.9%) than their
      female counterparts (33.3%). The percentage prevalence of the clinical signs of
      onchocerciasis in the farm settlement was hanging groin 14.1%, onchocercal
      nodules 25.1%, onchocercal dermatitis 27.6% and scrotal enlargement 3.7%. The
      percentage prevalence of the eye lesions among the onchocerciasis infected
      inhabitants was cataract 7.4%, glaucoma 3.7%, optic atrophy 0.6% and uveitis 18
      (5.5%). Impaired vision occurred among 80 (24.5%) inhabitants and blindness was
      reported among 2 (0.6%) inhabitants.

PMID- 12206039
TI  - Mass DEC campaign for filariasis in a hyper endemic district of West Bengal.
AB  - As a part of the on-going National Filaria Control Programme, National Filaria
      Day was observed in Purulia district of West Bengal on 26th Nov 2000 with an
      extensively organized mass DEC consumption campaign preceded by IEC activities
      and followed by mopping up operations. In all 81.07% of the targeted population
      was covered, females (84.3%) being more available than males (78.3%). Percentage
      of coverage declines with increase in age. Municipalities and notified areas had
      less coverage as well as supervised consumption than in other areas. Consumption
      was highest in Balarampur block (88.6%). Supervised consumption among surveyed
      population was highest in Bandwan (56.0%). Overall patient compliance was very
      good, with side effects of vomiting, dizziness, headache and fever being 2.12%
      only among surveyed population. Disease prevalence among population covered
      showed 0.1% hand swelling, 0.6 to 0.8% leg swelling, while 1.1% of males had
      hydrocele.

PMID- 12206040
TI  - Community perception of Malayan filariasis in the rural areas of Cherthala Taluk
      of Kerala State, south India.
AB  - Lymphatic filariasis, one of the major public health problems can be controlled
      with the active participation of the community. The human factors involved in the
      disease transmission are important. The knowledge on the community perception and
      practice is essential to develop community oriented control programmes. A
      descriptive study was conducted in the filariasis endemic area of Cherthala,
      Kerala State, India, to identify the level of people's perception on Malayan
      filariasis. Two methods namely, interviews and uncontrolled observation were used
      in the study. A total of 450 respondents (150 microfilaria carriers, 150 chronic
      patients and 150 normals) were interviewed. The study results showed that
      majority of the respondents (86.7%) were aware that the disease was caused by a
      parasite and 93.6% had awareness on transmission of the disease through mosquito
      bite. The knowledge on the preventive measures against filariasis was also high
      (78.2%) among the sampled respondents. The strategy for community mobilization in
      filariasis control programme is discussed in view of high awareness.

PMID- 12206041
TI  - Teachers awareness and opinion about AIDS--a study from eastern Nepal.
AB  - The potential for spread of HIV in Nepal is considered large because of the
      presence of extensive commercial sex workers, high rate of sexually transmitted
      disease, low condom use and many pockets of intravenous drug users. To prevent
      this disease from producing any public health problem in Nepal, strategies have
      been formulated by Government and non-government agencies in Nepal. School
      teachers' views and knowledge regarding HIV/AIDS are very important so that they
      can impart correct acknowledge about this dreaded disease AIDS to the school
      children who ultimately serve as catalytic agent to spread correct acknowledge in
      the community in long run. Teachers' awareness about HIV/AIDS in this study was
      fairly good. Majority of them were aware about established routes of HIV/AIDS
      transmission and various ways of preventing it. Various misconceptions regarding
      HIV transmission and its causes are the matter of concern. To impart education to
      the teachers and the community, more than 60% of the teachers expressed the radio
      to be the most effective medium. This can be suggested to the government to
      deliver more simple and attractive programmes about HIV/AIDS education through
      radio in suitable time for the community. The special AIDS education programme,
      for school teachers long term objective and with the support of government, non
      government and social organizations will go a long way in dissemination of health
      knowledge to the school children.

PMID- 12206042
TI  - Vertical transmission of dengue-2 virus through Aedes albopictus mosquitoes.

PMID- 12206043
TI  - Intestinal parasitic infection in the university campus of Aligarh.

PMID- 12206044
TI  - Seroprevalence of toxoplasmosis in HIV infected patients in Pondicherry.

PMID- 12206045
TI  - The Para Check-PC Test:--a simple rapid Dip stick test to detect Plasmodium
      falciparum infection.

PMID- 12206046
TI  - The assessment of pain behavior: implications for applied psychophysiology and
      future research directions.
AB  - Persons who have pain engage in behaviors such as resting in bed, taking
      medication, moving in a guarded fashion, or grimacing that communicate the fact
      that pain is being experienced. Pain-related behaviors increasingly are viewed as
      an important target in pain assessment. Traditionally, pain behavior has been
      assessed through interview or self-recording methods (e.g. diary records). Pain
      behaviors, however, are overt and can be recorded through direct observation.
      Over the past 20 years, observation methods have been developed to assess pain
      behavior in patients having persistent pain conditions. Although these methods
      are not widely used in applied psychophysiological settings, they potentially
      could be quite useful. The purpose of this paper is to review the literature on
      such observation methods. The paper is divided into five parts. The first part
      provides a description of the basic elements of pain behavior observation
      protocols. The second part presents information on the psychometric properties of
      the most commonly used protocols. The third part highlights applications of pain
      behavior observation protocols. The fourth part briefly describes the strengths
      and limitations of pain behavior observation. The paper concludes with a
      discussion of the implications of pain behavior observation for applied
      psychophysiology and future directions for research and practice in this area.

PMID- 12206047
TI  - Stress and psychophysiological dysregulation in patients with fibromyalgia
      syndrome.
AB  - Fibromyalgia syndrome (FMS) is a prevalent musculoskeletal pain disorder
      characterized by diffuse pain and associated psychophysiological symptoms.
      Despite extensive research in the past 3 decades, the etiology and
      pathophysiology of FMS and effective treatment approaches are yet to be
      delineated. Recently, it has been suggested that FMS may be related to
      hypofunctional stress systems, particularly in the autonomic nervous system (ANS)
      and the hypothalamic-pituitary-adrenal (HPA) axis. Studies have demonstrated that
      patients with FMS exhibit lowered sympathoadrenal reactivity to stress. These
      findings seem to be consistent with the large volume of research indicating the
      inverse relationship between pain sensitivity and sympathetic reactivity. In this
      paper, we discuss the role of stress in the pain experience in general, stress in
      patients with FMS, and review the studies evaluating the ANS and HPA functions in
      response to various stressors.

PMID- 12206048
TI  - Biofeedback in the treatment of headache and other childhood pain.
AB  - Since the first biofeedback (BFB) studies on pediatric pain were published in the
      early 1980s, most of the studies have focused on the treatment of pediatric
      migraine. More recently, BFB has also been evaluated in the treatment of tension
      headache in children. Not surprisingly, most of what we know about the efficacy
      and mechanisms of BFB in the treatment of children's pain problems concerns the
      treatment of childhood headache (HA). In this review, we provide a detailed
      summary of studies that have evaluated BFB in the treatment of childhood HAs with
      an emphasis on treatment outcome and maintenance of treatment success. Moreover,
      findings and hypotheses with regard to the mechanisms that may mediate the
      treatment effects of BFB are addressed. Finally, we discuss specific issues
      relating to the treatment of pain in children with BFB and outline future
      directions of research.

PMID- 12206049
TI  - Behavioral management of recurrent headache: three decades of experience and
      empiricism.
AB  - In the past three decades, behavioral interventions (chiefly relaxation,
      biofeedback, and stress-management) have become standard components of the
      armamentarium for management of migraine and tension-type headaches. Meta
      analytic literature reviews of these behavioral interventions have consistently
      identified clinically significant reductions in recurrent headache. Across
      studies, behavioral interventions have yielded approximately 35-50% reduction in
      migraine and tension-type headache activity. Although we have only recently begun
      to directly compare standard drug and nondrug treatments for headache, the
      available evidence suggests that the level of headache improvement with
      behavioral interventions may rival those obtained with widely used pharmacologic
      therapies in representative patient samples. In recent years, some attempts have
      been made to increase the availability and cost effectiveness of behavioral
      interventions through alternative delivery formats and mass communications.
      Recent developments within diagnosis and classification are summarized, pointing
      out implications for behavioral researchers. Select future directions are
      discussed, which include impact of the triptans, cost and cost effectiveness, and
      integration of behavioral treatments into primary care settings, the place where
      the great majority of headache sufferers receive treatment.

PMID- 12206050
TI  - Biofeedback and behavioral treatment of persistent pain in the older adult: a
      review and a study.
AB  - Persistent pain is a common health problem for older adults, age 60+, with a
      prevalence twice that in younger adults. Yet, older adults with chronic pain and
      headache are underrepresented in behaviorally oriented clinical programs that
      have proven effective for younger adults. A review of the literature indicates
      that older adults develop multiple pain-related problems that are similar to
      those of younger individuals. When offered the opportunity, older pain patients
      accept and benefit from multidisciplinary pain programs, cognitive-behavioral
      therapies and biofeedback training. A study comparing 58 older and 59 younger
      adults in a multidisciplinary pain program indicates that older pain patients
      readily acquire the physiological self-regulation skills taught in biofeedback
      assisted relaxation training, and achieve comparable decreases in pain for the
      pain program as a whole.

PMID- 12206051
TI  - On the pathophysiology of migraine--links for "empirically based treatment" with
      neurofeedback.
AB  - Psychophysiological data support the concept that migraine is the result of
      cortical hypersensitivity, hyperactivity, and a lack of habituation. There is
      evidence that this is a brain-stem related information processing dysfunction.
      This cortical activity reflects a periodicity between 2 migraine attacks and it
      may be due to endogenous or exogenous factors. In the few days preceding the next
      attack slow cortical potentials are highest and habituation delay experimentally
      recorded during contingent negative variation is at a maximum. These striking
      features of slow cortical potentials are predictors of the next attack. The
      pronounced negativity can be fed back to the patient. The data support the
      hypothesis that a change in amplitudes of slow cortical potentials is caused by
      altered habituation during the recording session. This kind of neurofeedback can
      be characterized as "empirically based" because it improves habituation and it
      proves to be clinically efficient.

PMID- 12206052
TI  - The modification of cortical reorganization and chronic pain by sensory feedback.
AB  - Recent neuroscientific evidence has revealed that the adult brain is capable of
      substantial plastic change in areas such as the primary somatosensory cortex that
      were formerly thought to be modifiable only during early experience. We discuss
      research on phantom limb pain as well as chronic back pain that revealed
      functional reorganization in both the somatosensory and the motor system in these
      chronic pain states. In phantom limb pain patients, cortical reorganization is
      correlated with the amount of phantom limb pain; in low back pain patients the
      amount of reorganizational change increases with chronicity. We present a model
      of the development of chronic pain that assumes an important role of
      somatosensory pain memories. In phantom limb pain, we propose that those patients
      who experienced intense pain prior to the amputation will later likely develop
      enhanced cortical reorganization and phantom limb pain. We show that cortical
      plasticity related to chronic pain can be reduced by behavioral interventions
      that provide feedback to the brain areas that were altered by somatosensory pain
      memories.

PMID- 12206053
TI  - Pollutants in house dust as indicators of indoor contamination.
AB  - This review summarizes occurrence of organic and inorganic contaminants in house
      dust and the contribution of house dust as a marker of indoor exposure. Several
      studies have identified house dust as an important route of toxicant exposure.
      Often levels of pollutants found in house dust, including compounds banned long
      ago, are significant sources of exposure for the general population, especially
      children. House dust is a sink and repository for semivolatile organic compounds
      and particle-bound matter. Analyses of compounds in house dust are a measure of
      indoor contamination but may also provide valuable information for assessment of
      human indoor exposure. The objective of analyzing house dust are to describe the
      extent, distribution, and determinants of exposure, to identify possible sources
      of indoor contamination, or to record elevated indoor exposure leading to
      intervention or sanitation. House dust and compounds adsorbed to house dust may
      enter the human body by inhalation of suspended and resuspended particles,
      through nondietary ingestion of dust, through ingestion of particles adhering to
      food, surfaces in the homes, and on the skin as well as by absorption through the
      skin. The quantity of dust inhaled and deposited in the differing parts of the
      alveolar tract is dependent on the aerodynamic diameter. Exposure to house dust
      does not exclusively and may not even predominantly occur via inhalation,
      however. For instance, ingestion of house dust particles adhering to food,
      objects, and the skin or direct absorption through the skin may be primary routes
      of exposure (Lewis et al. 1994). Samples referred to as "house dust" vary
      significantly because house dust may be of different origin, amount, and
      composition and the method of sampling the dust influences the properties of the
      sample used for analysis. Passive and active sampling methods are described and
      discussed. For the analysis of organic pollutants in house dust, the < or = 63
      microns fraction should be favored because variances caused by inhomogeneity of
      the subsample are low. Results from studies on house dust are presented for
      polychlorinated biphenyls (PCB), polycyclic aromatic hydrocarbons (PAH),
      plasticizers (phthalates, phenols), flame retardants, other organic xenobiotics,
      and inorganic constituents. If available, medians as a measure of the average
      concentration and the 90th or 95th percentiles are added as reference values. The
      review of the literature points out that ingestion of house dust may be a major
      route of exposure to pesticides for infants and toddlers. So far, only a few
      guideline values or limiting values for house dust exist. For lead in house dust,
      the health risk is regulated only in the U.S. and for PAH in the Federal Republic
      of Germany. Risk associated with the ingestion of contaminated dust by small
      children (age, 1-6 years; mean body weight, 16 kg) can be estimated using the
      chronic oral reference dose (RfD) and a daily intake of 100 mg house dust. The
      tentative benchmark house dust concentrations that are believed to be without
      health effect for small children were calculated for several compounds from their
      current RfD. Comparison with the maximum concentrations reviewed for
      chlorpyrifos, DDT, and diazinon indicates that the tolerable exposure
      concentration in house dust might be exceeded and that chlorpyrifos especially
      can be considered as a potential hazard to householders. The role of house dust
      as an exposure source is gaining more attention over the years but several open
      questions related to health remain to be resolved. Pesticides applied outside or
      within the household that are absorbed and preserved by house dust can lead
      through the everyday activities of children and infants to increased exposure.
      Residential exposure including house dust residues contribute to combined
      exposure from dietary and nondietary sources. It is justified to shift more
      attention to indoor pollution by house dust contamination and to improve the risk
      assessment of nondietary ingestion, but any health-based standard must be
      accompanied by a specific dust sampling method.

PMID- 12206054
TI  - Factors influencing levels of trace elements in human hair.
AB  - Hair, as a biological tissue, is unique in that it remains isolated from human
      metabolic activities and indicates concentration profiles of elements in an
      individual at a particular time period. However, hair concentrations of elements
      are affected by different factors that are also specific to certain regions and
      subjects. Many causal factors have been reported for element level changes in
      hair; however, in the future more new factors are likely to be reported. All the
      factors causing change in the hair levels of elements are grouped under four main
      categories: biological factors, personal factors, environmental factors, and
      analytical and methodological factors. Comparison of results of element levels in
      hair for certain factors shows different (positive, negative, or specific) trends
      because of regional variation. Regarding certain factors (age, sex, health,
      occupation, etc.), the influence causing the change in element levels is obvious,
      whereas the influence of other factors (structure of hair, height and weight of
      the subject, etc.) is obscure. It is very important to consider all the factors
      at the time of investigation for effective interpretation, validity, and
      application of results of hair analysis.

PMID- 12206056
TI  - Best foot forward.

PMID- 12206055
TI  - Abiotic hydrolysis of pesticides in the aquatic environment.
AB  - Hydrolysis of a pesticide is basically a reaction with a water molecule involving
      specific catalysis by proton or hydroxide, and sometimes inorganic ions such as
      phosphate ion, present in the aquatic environment that play a role in general
      acid-base catalysis. In this review, the basic profiles of hydrolysis such as pH
      and temperature dependencies are clarified for each class of pesticides together
      with typical reaction mechanisms. Although these hydrolytic profiles depend on
      the chemical structure and functional group(s) of a pesticide molecule, they are
      not always consistent within a chemical class of pesticides. For example,
      organophosphorus pesticides are primarily susceptible to alkaline hydrolysis with
      less acidic catalysis, but some of phosphorodithioates are found to be acid
      labile. In the case of carbamates, the pKa value of a leaving group is known to
      control their hydrolysis mechanism, whether BAC2 or E1cB. As one of the
      predictive approaches, the linear free-energy relationship has been successfully
      applied to hydrolysis of a series of organophosphorus and carbamate pesticides
      under conditions in which the reaction mechanism does not change. However, it
      still seems advantageous to estimate a priori hydrolytic profiles of pesticides,
      either because there is insufficient precision in the methodology or the chemical
      class is limited, or because of pH and temperature dependencies of hydrolysis.
      Therefore, it would still be practical, for the present, when investigating
      abiotic hydrolysis of a new pesticide that a laboratory study be effectively
      designed on the basis of accumulated knowledge of hydrolytic profiles for the
      essential chemical structure and functional groups and conducted to obtain pH-
      and temperature-rate profiles. Various instrumental techniques have been applied
      to chemical identification of degradates, leading to clarification of the
      reaction mechanisms involved, but greater use of computational methods such as ab
      initio and semiempirical molecular orbital calculations would be highly
      recommended for better understanding at a molecular level by considering the
      solvent effect (hydration). The chemical identification of degradates is usually
      cumbersome and challenging, especially when these are unstable species. The
      recent progress of LC-MS allows unstable or polar degradates to be identified
      more efficiently, and such knowledge will help researchers to hydrolytic
      processes more easily understand. Although testing guidelines being harmonized
      throughout the world afford valuable information on the basic profiles of
      hydrolysis, recent investigations on interactions of pesticides with dissolved
      organic matter and catalytic or inhibitive effects caused by metal ions, metal
      oxides, and clay seem to raise the question as to what degree laboratory and
      field data differ and how laboratory data can be more precisely extrapolated to
      field data. Moreover, pesticides are usually applied as a suitable formulation,
      and thus the effects of surfactants and other formulation reagents on hydrolysis
      should be examined in more detail. To assess the fate and impact of pesticides
      and their degradates in real aquatic environments, these concerns should be
      further examined using the various analytical techniques together with simulation
      models.

PMID- 12206057
TI  - Out of reach.

PMID- 12206058
TI  - Special relationship.

PMID- 12206059
TI  - Patient satisfaction with chronic pain management.
AB  - BACKGROUND: This article describes the use of focus groups in research, including
      the advantages and disadvantages of using this type of research methodology.
      Using an example of a focus group of patients who experienced chronic pain, the
      authors discuss the planning, organisation, conduct and analysis of focus groups.
      CONCLUSION: Focus groups enabled an exploration of the topics in-depth including
      obtaining insight from a patient's perspective of the management of their chronic
      pain. It was important and of value to take into account the experiences and
      expectations of health service delivery from a consumer's perspective.

PMID- 12206060
TI  - The mental health needs of patients in physical care settings.
AB  - Mental health problems are frequently seen in physical care settings. The author
      gives an overview of different types of psychological illness and discusses
      appropriate treatment and management.

PMID- 12206061
TI  - Peer-led and adult-led school drug prevention: a meta-analytic comparison.
AB  - Several studies have suggested that peer-led drug prevention programs are more
      effective than adult-led programs, but the evidence is not conclusive. In this
      article the results are presented of a meta-analysis of studies that compare drug
      prevention programs led by peers to the same programs led by adults. Twelve
      studies were identified in a systematic literature search. The quality of these
      studies was not optimal, and the interventions and target groups differed
      considerably among studies. Overall, peer-led programs were found to be somewhat
      more effective than adult-led programs (standardized difference d: 0.24). Large
      differences between studies were found, with some studies indicating greater
      effects for peer-led programs and other studies showing greater effects for adult
      led programs. It is concluded that the effectiveness of a prevention program is
      determined by several characteristics of the programs. The leader may constitute
      one of those characteristics.

PMID- 12206062
TI  - Development and immediate impact of a self-instruction curriculum for an
      adolescent indicated drug abuse prevention trial.
AB  - This article describes the development and immediate impact of a self-instruction
      indicated drug abuse prevention program, Project Towards No Drug Abuse (TND).
      Self-instruction programming often is used to help youth that are at high risk
      for dropout and drug abuse to complete their high school education, and is a
      method of choice among educators at alternative high schools. This article
      describes the justification for the self-instruction program, keys to good
      programmed self-learning, and how a 12-session health educator delivered program
      was converted to a self-instruction format. In addition, the immediate impact of
      a 3-group experimental trial is presented. Health educator led, self-instruction,
      and standard care control conditions are compared on knowledge change, and the
      two program conditions are compared on process ratings. Self-instruction
      programming can be successfully adapted from a health educator-led format, though
      the lack of student group interaction in this modality may limit its receptivity
      among students.

PMID- 12206063
TI  - Comparing drug use between welfare-receiving arrestees and non-welfare-receiving
      arrestees.
AB  - The Personal Responsibility and Work Opportunity Reconciliation Act of 1996
      (PRWORA) symbolized a comprehensive change to the nation's welfare system.
      Despite several provisions within PRWORA that focus on the use of illegal drugs,
      few studies have attempted to identify the prevalence of illegal drug use among
      welfare recipients. Moreover, no scholarly works have compared rates of drug use
      in welfare-receiving populations to those of non-welfare-receiving populations
      with an objective measure of drug use. In the current study, urine specimens were
      collected from 1,572 arrestees interviewed through Houston's Arrestee Drug Abuse
      Monitoring (ADAM) Program in 1999. Drug positive rates are compared between
      welfare-receiving arrestees (n = 116), non-welfare receiving arrestees living
      below the poverty level (n = 539), and non-welfare receiving arrestees living
      above the poverty level (n = 917). Welfare-receiving arrestees were more likely
      to be female, older, less educated, and to test positive for opiates and
      benzodiazepines than the other subgroups. Implications for welfare reform policy
      are discussed in light of the current findings.

PMID- 12206064
TI  - Attendance problems and disciplinary procedures in Nebraska schools.
AB  - STUDY PURPOSE: School principals were surveyed in rural and urban Nebraska
      schools to compare policies and procedures on school attendance, and to contrast
      the use of disciplinary procedures for attendance, violence and substance abuse.
      METHODS: A survey was sent to a 50 percent random sample of Nebraska schools.
      Respondent school addresses in metropolitan statistical areas (MSA) areas were
      categorized as urban, and non-MSA respondents were classified as rural area
      schools. RESULTS: Of the 680 surveys mailed, 464 (68.2 percent) completed surveys
      were returned. Overall, 86.2 percent of respondents were from rural schools and
      13.8 percent from urban schools. A list of disciplinary problems and procedures
      was reported for a first-time offense by rural and urban schools. Both an
      "occasional attendance problem" and a "chronic attendance problem" were most
      frequently addressed through parent contact in both urban and rural areas. For
      "fighting with another student," rural schools most commonly reported discipline
      by teacher, followed by discipline by principal and parent contact. In urban
      schools, discipline by principal was most common. For "using drugs other than
      alcohol or tobacco at school" in both areas, disciplinary procedures included
      parent contact and short-term suspension. A list of disciplinary problems and
      procedures was also reported for a second-time offense and third-time offense.
      For "fighting with another student," the most commonly reported procedure was
      discipline by principal and parent contact for a second-time offense, followed by
      short-term suspension and long-term suspension for a third-time offense. For
      "using drugs other than alcohol or tobacco at school," for a second time offense
      was long-term suspension and semester expulsion for a third-time offense.
      Principals were also asked in an open-response format, what program or procedures
      were currently in place to prevent violence in their school. Common responses
      were "conflict resolution training," followed by "the Boys Town social skills and
      behaviors model" and "a zero tolerance policy." CONCLUSIONS: School principals
      generally reported similar disciplinary actions for most disciplinary problems.
      For recurrent offenses and for serious problems, principals generally used
      tougher disciplinary procedures. Some of the discrepancies in disciplinary
      actions, however, suggest the need for consistent enforcement and communication
      of policies for both urban and rural schools.

PMID- 12206065
TI  - Needle and syringe cleaning practices among injection drug users.
AB  - Bleach-mediated disinfection (BMD) of needles and syringes (NS) has been
      advocated as a risk-reduction intervention against HIV among injection drug users
      (IDUs). The effect of needle exchange on the BMD practices of 176 NS-sharing IDUs
      was evaluated. IDUs were randomly assigned to either 1) Pharmacy Sales Condition,
      access to NS via legal sales of nonprescription NS; or 2) Needle Exchange
      Condition, with additional access to NS via an experimental needle exchange
      program. Repeated measures analysis revealed a main effect of time on BMD, no
      effect of assignment condition, and no time by assignment interaction. Logistic
      regression revealed IDUs who traded sex for money or drugs were less likely to
      practice BMD, and IDUs who reported a reduced number of sex partners were more
      likely to practice BMD. Future interventions should incorporate behavioral BMD
      components and address the concerns of those who trade sex for money or drugs.

PMID- 12206066
TI  - The expected personality characteristics of alcohol-dependent individuals.
AB  - The Big Five personality factors were used as a framework for examining the
      expected personality characteristics of individuals who are alcohol-dependent. In
      an experimental study, participants used a measure of the Big Five personality
      factors to rate two individuals, each described with either signs of alcohol
      dependence or not. The ratings of the participants showed that they expected the
      alcohol-dependent versions of both individuals to be less agreeable and less
      conscientious. The participants expected the alcohol-dependent college student to
      be more extraverted and the alcohol-dependent lawyer-father to be more neurotic.
      The expected personality characteristics of the alcohol-dependent versions of the
      two described persons were very similar to the actual personality characteristics
      of alcohol-dependent individuals. The results were consistent with prior findings
      regarding narrow-band personality traits related to the Big Five. The results
      help explain prior findings about the social handicap of problem drinking with
      regard to making friends, dating, marriage, and working. The findings have
      potential use in alcohol-problem prevention and treatment.

PMID- 12206067
TI  - Pancreatic cancer in West Virginia: results from a rural academic medical center.
AB  - Pancreatic cancer accounts for over 28,000 deaths a year in the United States.
      Since incidence rates and outcomes in a rural academic hospital setting have not
      previously been reported, we reviewed all patient records at Ruby Memorial
      Hospital in Morgantown from 1/90 to 12/99. Our study revealed 32,231 cancer
      patients during this time, of which 152 (0.5 percent) were diagnosed with
      pancreatic cancer. Only 32 (21.2 percent) patients had resectable tumors at time
      of diagnosis. The mean age of these patients was 67 years (range 34-83 years) and
      only 36 percent of operable patients were male. The majority of tumors (26 or 81
      percent) were found in the pancreatic head, and 97 percent of the tumors were
      adenocarcinomas. Only three patients (9.3 percent) had well-differentiated
      tumors, with poorly and moderately differentiated histologies making up 40
      percent and 50 percent, respectively. Operations performed included
      pancreaticoduodenectomy in 26 patients, total pancreatectomy in four patients,
      and distal pancreatectomy in two patients. There was only one perioperative death
      (3.1 percent). A total of 75 percent of the of the group underwent postoperative
      chemotherapy, mostly with fluorouracil-based monotherapy. Postoperative survival
      rate was 47 percent at one year, 25 percent at two years, and 9.6 percent at
      three years. No survival advantage was demonstrable in adjuvant treated patients.
      Our results show for the first time that pancreatic cancer is managed well in a
      rural hospital setting with equivalent short and long-term outcomes. The social
      and economic advantages of local patient care are supported by these results and
      warrant further study.

PMID- 12206068
TI  - The diagnosis and treatment of childhood melanoma.
AB  - The incidence of melanoma in prepubertal children is 0.3% to 0.4%, with 2 percent
      of all melanomas occurring in patients under the age of 20 years. Superficial
      spreading and nodular melanomas are the most common subtypes in childhood
      melanoma. This article describes conditions associated with an increased
      incidence of juvenile melanoma and how to best manage this disease.

PMID- 12206069
TI  - Contemporary management of renal trauma.
AB  - The genitourinary tract is frequently involved in various types of trauma to the
      chest, abdomen and pelvis. Genitourinary trauma is typically divided into upper
      tract trauma and lower tract trauma. Upper tract trauma involves injury to kidney
      and ureter while lower tract trauma typically involves bladder or urethral
      injury. This review will focus on current trends in the diagnosis, evaluation and
      treatment of renal trauma.

PMID- 12206070
TI  - Regional ileitis, Eisenhower and the Greenbrier.

PMID- 12206071
TI  - Changing minds.

PMID- 12206072
TI  - Making sense of cancer.

PMID- 12206073
TI  - Clinical governance for nurses: smoking cessation interventions.
AB  - AIM: To raise clinical governance issues by drawing on a Health Education
      Authority-sponsored review of the style, form and effect of a smoking cessation
      service in north west Lancashire. This service operated for five years before the
      government's decision to set up smoking cessation services. METHOD: A postal
      survey was undertaken of 800 clients. RESULTS: 193 people responded. Of these,
      132 (68 per cent) claimed to be helped by the service. Proactive telephone
      contact, carbon monoxide monitoring, the six-week course, nicotine replacement
      therapy, and reading materials were well received. Thirty six per cent of the
      respondents were not smoking at the time of the survey. CONCLUSION: Nursing staff
      are increasingly expected to provide smoking cessation support. The government is
      funding this work and monitoring the number of clients helped, rather than the
      quality of the service. However, in terms of clinical governance, the quality of
      the service is crucially important.

PMID- 12206074
TI  - Developing a learning pathway for student nurses.
AB  - It is essential to ensure equity and consistency of clinical learning for student
      nurses who will inevitably work in a variety of practice settings. This article
      describes the development of a learning pathway in response to the need to
      improve the quality of learning outcomes in the clinical environment. The North
      Devon and Exeter model uses a three-step approach, with particular emphasis on
      the preparation for clinical placements. The model gives equal responsibility to
      students and clinical staff, promoting a partnership, which takes the student
      through a quality learning experience. The philosophy that clinical learning
      should be enjoyable, stimulating and inspirational underpins the structure of the
      pathway.

PMID- 12206075
TI  - Hepatitis C: transmission, treatment and occupational risk.
AB  - There is a risk to nurses of contracting hepatitis C through occupational
      exposure, although in the UK infection is mainly limited to intravenous drug
      users. In this article Peter Washer discusses what is currently known about the
      virus, mainly focusing on transmission, treatment and the risk of occupational
      exposure.

PMID- 12206076
TI  - Managing post-operative nausea and vomiting.
AB  - Post-operative nausea and vomiting leads to unnecessary suffering for many
      surgical patients. Improved nursing management can help prevent and better treat
      this condition.

PMID- 12206077
TI  - Walking the talk. Interview by Frances Pickersgill.

PMID- 12206078
TI  - AIDS forcing exodus from Africa.

PMID- 12206079
TI  - The last straw.

PMID- 12206080
TI  - Community spirit.

PMID- 12206081
TI  - At the learning stage.

PMID- 12206082
TI  - Damage control.

PMID- 12206083
TI  - Listen, share, then lead.

PMID- 12206084
TI  - Stress buster.

PMID- 12206085
TI  - Food for thought.

PMID- 12206086
TI  - Coughs and colds: nurse management of upper respiratory tract infection.
AB  - BACKGROUND: Nurses in general practice are increasingly managing minor illness.
      This literature review examines the management of upper respiratory tract
      infection (URTI) as one area of patient care where nurses can make a major
      contribution. CONCLUSION: The challenge for nurses is to respond to the changing
      healthcare environment creatively and in collaboration with doctors and patients.

PMID- 12206087
TI  - Empowerment for adults with chronic mental health problems and obesity.
AB  - Obesity is a major health risk and a common problem among people with mental
      health problems. This article examines the role of empowerment within a health
      promotion framework for overweight and obese adults with chronic mental health
      problems. Behaviour change, while a valid strategy for health promotion, might
      not achieve the desired health gain. On the other hand, an empowered individual
      or community is able to bring about positive and permanent change by mobilising
      the necessary resources to achieve health.

PMID- 12206088
TI  - Blood and the classification of anaemia.
AB  - This article gives a brief overview of the function and composition of blood,
      focusing on the red blood cell and the development of the various types of
      anaemia. Good patient care and effective treatment of this complex condition is
      dependent on informed nursing practice.

PMID- 12206089
TI  - [Akseli Gallen-Kallela: The curse of Kullervo 1899].

PMID- 12206091
TI  - Are prevention programs falling prey to political pressure?
AB  - AIDS advocates and clinicians express alarm about an investigation that has been
      launched targeting all federally funded HIV/AIDS prevention programs. The
      Department of Health and Human Services intends to assess the programs' materials
      to make certain they adhere to 1992 requirements of the Centers for Disease
      Control and Prevention. Critics say these programs already are thoroughly
      reviewed by local program review panels that assess content according to
      community obscenity standards and that the federal government should not second
      guess their decisions. Meanwhile, the investigation has already resulted in one
      state turning down an HIV/AIDS prevention project until it's given a green light
      by the feds.

PMID- 12206090
TI  - [Unnecessary visits?].

PMID- 12206093
TI  - Special report: federal AIDS prevention funding at risk. The letter that launched
      federal 'obscenity' audits. Thompson writes to Rep. Mark E. Souder.
AB  - Here's the Bush administration letter that was the first step toward
      investigating all federally funded HIV prevention programs.

PMID- 12206092
TI  - Research shows targeted HIV prevention succeeds.
AB  - Systematic reviews of HIV prevention intervention literature for the target
      populations of African-Americans, Latinos, youths, and men who have sex with men
      in the United States shows that targeted interventions work in reducing HIV risk
      behaviors. Interventions that succeeded were culturally sensitive, of longer
      duration, and included skills training, according to a project supported by the
      Surgeon General's Leadership Campaign on AIDS and teh California HealthCare
      Foundation in Oakland.

PMID- 12206094
TI  - Special report: federal AIDS prevention funding at risk. Here is how obscenity
      issue was raised.
AB  - Obscenity may be in the eye of the community beholder, but that apparently won't
      stop the federal government from taking a peek. Federal officials are conducting
      comprehensive reviews of all CDC-funded HIV/AIDS program activities, and federal
      funding for HIV/AIDS prevention programs now is at risk if local review panels
      fear that the materials could be considered obscene by federal officials. The
      federal reviews also will assess whether these programs are adhering to CDC
      prevention material requirements.

PMID- 12206095
TI  - Special report: federal AIDS prevention funding at risk. 1992 CDC guidelines
      spell out dos and don'ts.
AB  - The Centers for Disease Control and Prevention has asked all HIV prevention grant
      recipients to review their HIV/AIDS prevention materials to make certain these
      meet the CDC's requirements. Here is an abridged reprint of what's in the
      guidelines.

PMID- 12206096
TI  - In memoriam. Claude Poyart, M.D. (1933-2001).

PMID- 12206097
TI  - Update on women and HIV.

PMID- 12206098
TI  - Adolescents and HIV.

PMID- 12206099
TI  - HLA B57 and abacavir hypersensitivity.

PMID- 12206100
TI  - IQs, VIQs, and NIQs: are we smart yet?

PMID- 12206101
TI  - TB and HIV: challenges and progress.

PMID- 12206102
TI  - Update on opportunistic infections.

PMID- 12206103
TI  - AIDS and boundaries: instinct versus empathy.

PMID- 12206104
TI  - Editorial: the third person.

PMID- 12206105
TI  - Boundaries and HIV-related case management.

PMID- 12206106
TI  - Report from the XI International Conference. Psychological distress and support.

PMID- 12206107
TI  - Editorial: unanswered questions.

PMID- 12206108
TI  - Two worlds: one conference.

PMID- 12206109
TI  - Death anxiety and HIV disease.

PMID- 12206110
TI  - Editorial: imagining anxiety.

PMID- 12206111
TI  - Anxiety and anxiety disorders.

PMID- 12206112
TI  - HIV-related mental health in correctional settings.

PMID- 12206113
TI  - Editorial: jailhouse rights.

PMID- 12206114
TI  - Late-stage AIDS and prison populations.

PMID- 12206115
TI  - Intimacy and safer sex.

PMID- 12206116
TI  - Editorial: intimate understanding.

PMID- 12206117
TI  - Gay men and intimacy: missing link in HIV prevention.

PMID- 12206118
TI  - HIV incidence trends among gay and bisexual men.

PMID- 12206119
TI  - Editorial: surveying HIV.

PMID- 12206120
TI  - The AIDS epidemic among women in the United States.

PMID- 12206121
TI  - The changing picture of HIV: a chronic illness, again?

PMID- 12206122
TI  - Editorial: chronic unease.

PMID- 12206123
TI  - Being chronically ill.

PMID- 12206124
TI  - U.S. Supreme Court refuses to hear case of Atlanta dental hygienist.

PMID- 12206125
TI  - Manganese: miracle or myth?

PMID- 12206126
TI  - Advanced directives--tools for empowerment.

PMID- 12206128
TI  - When anger becomes rage: working with threatening clients.

PMID- 12206127
TI  - Task force on the management of chest pain.

PMID- 12206129
TI  - Establishing a safe environment.

PMID- 12206130
TI  - Purity, pragmatism and hip protector pads.

PMID- 12206131
TI  - The continued evolution of hyphenated instruments.

PMID- 12206132
TI  - Hyphenated techniques--the most commonly used method for trace elemental
      speciation analysis.

PMID- 12206133
TI  - Ischemic stroke secondary to vertebral and cartid artery dissection following
      chiropractic manipulation of the cervical spine.

PMID- 12206134
TI  - [Physiopathology of the respiratory system and hypersensitivity and its clinical
      diagnosis].

PMID- 12206135
TI  - The drug efflux pump MRP2: regulation of expression in physiopathological
      situations and by endogenous and exogenous compounds.
AB  - The multidrug resistance-associated protein 2 (MRP2) is an ATP-binding cassette
      transporter involved in biliary, renal, and intestinal secretion of numerous
      organic anions, including endogenous compounds such as bilirubin and exogenous
      compounds such as drugs and toxic chemicals. Its expression can be modulated in
      various physiopathological situations, notably being markedly decreased during
      liver cholestasis and upregulated in some cancerous tissues. In addition, MRP2
      levels are altered in hepatocytes in response to hormones such as glucocorticoids
      and to structurally unrelated drugs such as rifampicin, phenobarbital, ritonavir,
      and cisplatin. The chemical carcinogen 2-acetylaminofluorene and chemopreventive
      agents such as oltipraz and sulforaphane also markedly increased MRP2 expression
      in liver parenchymal cells. Interestingly, most of the chemical inducers of MRP2
      act on drug-metabolizing enzymes, indicating a coordinated regulation of these
      detoxifying proteins; cellular mechanisms involved are, at least partly, common
      and may be related to nuclear hormone receptors such as the pregnane X receptor.
      Owing to the major role played by MRP2 in elimination of drugs and endogenous
      compounds, modulation of its expression may lead to adverse effects or to changes
      in drug pharmacokinetics.

PMID- 12206136
TI  - In vitro cytotoxicity of the organophosphorus insecticide methylparathion to FG
      9307, the gill cell line of flounder (Paralichthys olivaceus).
AB  - FG-9307, a cell line derived from the gill of flounder Paralichthys olivaceus,
      was used to determine the acute cytotoxic effects of the organophosphorus
      insecticide methylparathion. The cytotoxic effects of methylparathion were
      initially measured by three endpoint systems: neutral red (NR) uptake assay,
      tetrazolium (MTT) assay, and cell protein assay. Results indicated that
      concentrations of methylparathion ranging from 5 microg/ml to 60 microg/ml were
      toxic, and there was no significant difference in cytotoxic effects between the
      three test systems. Thus, the FG-9307 cell line is one of several choices for
      evaluating the acute toxicities of organophosphorus insecticides such as
      methylparathion. The ultrastructure of the cells was also studied. It was found
      that the ultrastructure of the cells was markedly altered by methylparathion, as
      evidenced by dilation of mitochondria, breakdown of rough endoplasmic reticulum,
      nuclear necrosis, and production of numerous lysosomes and lipid vacuoles. This
      appears to be the first report that a marine fish cell line can be used for acute
      in vitro cytotoxicity evaluation of methylparathion.

PMID- 12206137
TI  - All-trans-retinoic acid-mediated modulation of p53 during neural differentiation
      in murine embryonic stem cells.
AB  - All-trans-retinoic acid (RA) plays an important physiological role in embryonic
      development and is teratogenic in large doses in almost all species. p53, a tumor
      suppressor gene encodes phosphoproteins, which regulate cellular proliferation,
      differentiation, and apoptosis. Temporal modulation of p53 by retinoic acid was
      investigated in murine embryonic stem cells during differentiation and apoptosis.
      Undifferentiated embryonic stem cells express a high level of p53 mRNA and
      protein followed by a decrease in p53 levels as differentiation proceeds. The
      addition of retinoic acid during 8-10 days of differentiation increased the
      levels of p53 mRNA and protein, accompanied by accelerated neural differentiation
      and apoptosis. Marked increase in apoptosis was observed at 10-20 h after
      retinoic acid treatment when compared with untreated controls. Retinoic acid
      induced morphological differentiation resulted in predominantly neural-type
      cells. Maximum increase in p53 mRNA in retinoic acid-treated cells occurred on
      day 17, whereas maximum protein synthesis occurred on days 14-17, which coincided
      with increased neural differentiation and proliferation. Increased p53 levels did
      not induce p21 transactivation, interestingly a decrease in p21 was observed on
      day 17 on exposure to retinoic acid. The level of p53 declined by day 21 of
      differentiation. The results demonstrated that retinoic acid-mediated apoptosis
      preceded the changes in p53 expression, suggesting that p53 induction does not
      initiate retinoic acid-induced apoptosis during development. However, retinoic
      acid accelerated neural differentiation and increased the expression of p53 in
      proliferating neural cells, corroborated by decreased p21 levels, indicating the
      importance of cell type and stage specificity of p53 function.

PMID- 12206138
TI  - Ozone-mediated cytotoxicity after short-term exposure and its relation to the
      production of cellular metabolites (NO, H2O2).
AB  - Alveolar macrophages secrete numerous mediators, playing an important role in
      host defence. Among these mediators, nitric oxide (NO) and hydrogen peroxide
      (H2O2) are both involved in bactericidal killing and trigger the release of other
      cellular metabolites. We have analyzed the effect of an atmosphere polluted with
      ozone (0.03-0.5 ppm v/v) on the monocytic cell line THP-1, as a model for
      alveolar macrophages, in vitro. NO and H2O2 were chosen to evaluate cell response
      to ozone. Cell injury was evaluated using lactate dehydrogenase (LDH) liberation
      into the medium. An exposure to 0.5 ppm ozone proved to be more toxic to the
      cells, than 0.1 or 0.03 ppm, evidenced by more LDH being liberated and
      cytotoxicity reaching values up to 64%. For all ozone concentrations, H2O2
      production reached a peak value after 10-15 min of exposure, after which the
      concentration of extracellular H2O2 production diminished rapidly. The highest NO
      concentrations were measured with 0.5 ppm ozone, reaching a maximum value of 1460
      nmol/L per 5 x 10(6) cells, which is 1.55 times higher than for nonexposed cells.
      Lower concentrations barely induced higher NO concentrations compared to
      nonexposed cells. The results indicate that ozone effects not only the viability
      of human monocytes but also the release of antibacterial and defense signaling
      molecules and suggest that ozone-mediated cytotoxicity may be related to the
      secretion of NO and H2O2.

PMID- 12206139
TI  - Population growth kinetics and bulk membrane lipid alterations in Tetrahymena
      pyriformis: exposure to pentachlorophenol.
AB  - This study describes effects of exposure of the freshwater ciliate Tetrahymena
      pyriformis to the "classic" weak acid respiratory uncoupler pentachlorophenol
      (PCP) on the population growth kinetics and membrane lipid profiles. The
      assessment of growth kinetics of naive populations exposed to PCP, at
      concentrations eliciting < 50% growth inhibition, showed generation times of
      exposed cultures similar to generation times of controls but preceded by a short
      lag phase (< 2 h). Assessment of exposed cultures exhibiting > 50% growth
      inhibition revealed generation times that increased with increasing
      concentrations of toxicant. In addition, the relative percentages of selected
      fatty acid methyl esters (FAMEs) in both pellicle and mitochondrial membranes
      were examined. Upon exposure to PCP the relative percentages of FAMEs 12:0, 14:0,
      16:0, 16:1, and 18:0 did not change. However, with exposure to PCP a decrease was
      observed for FAMEs 15:0 and 17:0. Conversely, with PCP exposure there was an
      increase in FAME 18:1. A comparison of these results with those elicited upon
      exposure to the model narcotic 1-octanol reveals marked differences in both
      growth kinetics and fatty acid shifts.

PMID- 12206140
TI  - DNA damage in human colonic mucosa cells evoked by nickel and protective action
      of quercetin - involvement of free radicals?
AB  - Nickel is a toxic and carcinogenic environmental and occupational pollutant and
      quercetin is a dietary flavonoid that is reported to modulate effects of many
      mutagens and carcinogens. We investigated the ability of nickel chloride to
      induce DNA damage in human colonic mucosa cells in the presence of quercetin,
      using the alkaline comet assay. Nickel chloride (5-250 micromol/L) evoked dose
      dependent DNA damage and quercetin at 50 micromol/L decreased the extent of this
      damage. The cells exposed to nickel chloride progressively removed their DNA
      damage and the presence of 50 micromol/L quercetin in the repair-incubation
      medium did not affect the repair kinetics. Cells exposed to nickel and treated
      with endonuclease III, an enzyme recognizing oxidized bases, displayed a greater
      extent of DNA damage than those not treated with the enzyme. Quercetin did not
      exert a significant effect on the production of oxidized bases by nickel.
      Pretreatment of the cells with a nitrone spin trap, N-tert-butyl-alpha
      phenylnitrone, decreased the extent of DNA damage evoked by nickel. Quercetin
      caused a further decrease in the extent of the damage in the presence of the
      trap. The results obtained suggest that reactive oxygen species, including free
      radicals, might be involved in the formation of DNA lesions induced by nickel
      chloride in colonic mucosa cells and that quercetin may exert protective effects
      in these cells.

PMID- 12206141
TI  - Lupus: immunity gone awry.

PMID- 12206142
TI  - My skin has become drier and more fragile as I've aged. Why is that, and what can
      I do about it?

PMID- 12206143
TI  - I've been diagnosed with carpal tunnel syndrome. Should I have surgery?

PMID- 12206145
TI  - Stopping heavy periods. For some women, endometrial ablation is a viable
      alternative to hysterectomy.

PMID- 12206144
TI  - Choosing an antidepressant. Finding the right drug often requires patience.

PMID- 12206147
TI  - Newfangled pacemaker helps with heart failure.

PMID- 12206146
TI  - COX-2 inhibitors: better than traditional NSAIDs? Vioxx and Celebrex may be no
      less risky than NSAIDs.

PMID- 12206148
TI  - Whole grains, two drinks a day may help repel type 2 diabetes.

PMID- 12206149
TI  - Insect repellent report card.

PMID- 12206151
TI  - Lightning safety tips.

PMID- 12206150
TI  - Added golden years from smoking cessation.

PMID- 12206152
TI  - Reduced fat is not equal to low calorie.

PMID- 12206153
TI  - The usefulness of serum adenosine deaminase 2 (ADA2) activity in adults for the
      diagnosis of pulmonary tuberculosis.
AB  - Rapid diagnosis of Mycobacterium tuberculosis remains an obstacle for therapy of
      tuberculosis (TB). Adenosine deaminase isoform 2 (ADA2) is produced by activated
      macrophages and has been used for diagnosis of TB from extra-pulmonary sites.
      However, few studies adequately address whether serum ADA2 activity is useful for
      diagnosis of active pulmonary tuberculosis (PTB). We prospectively measured serum
      ADA2 activity in 110 patients with pulmonary disease (65 cases with active PTB
      and 45 cases with other respiratory diseases) and 78 healthy volunteers (eight
      with tuberculin skin test positive). The serum ADA2 for the diagnosis of PTB had
      the sensitivity of 36.9%, the specificity of 84.5%, the positive predictive value
      of 10.9% and the negative predictive value of 96.2%. We concluded that serum ADA2
      activity is neither useful to diagnosis of active PTB nor to differentiate from
      other respiratory diseases.

PMID- 12206155
TI  - JAMA patient page. Carbon monoxide poisoning.

PMID- 12206154
TI  - Things to know and do about cancer clusters.
AB  - Perceived cancer clusters present difficulties and opportunities for clinicians
      and public health officials alike. Public health officials receive reports of
      perceived cancer clusters, evaluate the validity of these reports, and/or launch
      investigations to identify potential causes. Clinicians interact directly with
      the affected patients, families, or community representatives who question the
      occurrence of cancer and the underlying causes. Clinicians may identify cancer
      clusters when they question the unusual occurrence of a rare form of cancer
      within their practice or community. In addition, clinicians may be asked to
      discuss cancer clusters and inform local debates. In this paper, we describe the
      public health practice experience with cancer clusters and identify cancer
      prevention and control opportunities for clinicians and public health officials.
      Scientific investigations of cancer clusters rarely uncover new knowledge about
      the causes of cancer. However, a set of common characteristics, unique to
      etiologic cluster investigations have uncovered new information about the causes
      of cancer or demonstrated a preventable link to a known carcinogen. These
      characteristics may provide useful clues for sorting out the small number of
      clusters worthy of further scientific investigation. Public awareness of cancer
      clusters may promote an opportunity to inform and motivate people about the
      preventable causes of cancer and effective cancer screening methods.

PMID- 12206156
TI  - Screening for diabetes.

PMID- 12206157
TI  - Quiz page. Transplant glomerulopathy.

PMID- 12206158
TI  - Health and healing in twentieth-century African history. (Introduction to his
      volume, Dis-Ease in the Colonial State).

PMID- 12206159
TI  - Theory and simulation of buoyancy-driven convection around growing protein
      crystals in microgravity.
AB  - We present an order-of-magnitude analysis of the Navier-Stokes equations in a
      time-dependent, incompressible and Boussinesq formulation. The hypothesis
      employed of two different length scales allows one to determine the different
      flow regimes on the basis of the geometrical and thermodynamical parameters
      alone, without solving the Navier-Stokes equations. The order-of-magnitude
      analysis is then applied to the field of protein crystallization, and to the flow
      field around a crystal, where the driving forces are solutal buoyancy-driven
      convection, from density dependence on species concentration, and sedimentation
      caused by the different densities of the crystal and the protein solution. The
      main result of this paper is to provide predictions of the conditions in which a
      crystal is growing in a convective regime, rather than in the ideal diffusive
      state, even under the typical microgravity conditions of space platforms.

PMID- 12206161
TI  - CECILIA, a versatile research tool for cellular responses to gravity.
AB  - We describe a centrifuge designed and constructed according to current demands
      for a versatile instrument in cellular gravitational research, in particular
      protists (ciliates, flagellates). The instrument (called CECILIA, centrifuge for
      ciliates) is suited for videomonitoring, videorecording, and quantitative
      evaluation of data from large numbers of swimming cells in a ground-based
      laboratory or in a drop tower/drop shaft under microgravity conditions. The
      horizontal rotating platform holds up to six 8mm-camcorders and six chambers
      holding the experimental cells. Under hypergravity conditions (up to 15 g)
      chambers can be rotated about 2 axes to adjust the swimming space at right angles
      or parallel to the resulting gravity vector. Evaluations of cellular responses to
      central acceleration-- in the presence of gravitational 1 g--are used for
      extrapolation of cellular behaviour under hypogravity conditions. CECILIA is
      operated and monitored by computer using a custom-made software. Times and slopes
      of rising and decreasing acceleration, values and and quality of steady
      acceleration are supervised online. CECILIA can serve as an on-ground research
      instrument for precursor investigations of the behaviour of ciliates and
      flagellates under microgravity conditions such as long-term experiments in the
      International Space Station.

PMID- 12206160
TI  - Bacteriorhodopsin crystal growth in reduced gravity--results under the
      conditions, given in CPCF on board of a Space Shuttle, versus the conditions,
      given in DCAM on board of the Space Station Mir.
AB  - For the purpose of bio-electronics, bacteriorhodopsin was crystallized into two
      habits through liquid-liquid-diffusion, namely individual needles of up to 1.9 mm
      in length and needle bunch-like clusters of up 4.9 mm in total length. In both
      the reduced gravity experiments performed, the morphology of the individual
      needles (crystal form A) had improved in terms of sharp needle edges and compact
      needle packing, compared to the parallel ground controls. For the long duration
      wide range low gravity condition in the "Diffusion-controlled Crystallization
      Apparatus for Microgravity (DCAM)" on Mir (STS-89 up), needle bunches on average
      were longer there than on the ground, while the compactness of the clusters, i.e.
      the average ratio of clustered length to clustered width was the reverse. Some
      exceptionally large individuals needles were grown in DCAM. For the "Commercial
      Protein Crystallization Facility (CPCF)" in short duration high definition
      microgravity conditions during a science mission of the Space Shuttle Discovery
      (STS-95), size and shape of the individual needles were homogeneous and superior
      to those of both the parallel ground controls and the results in DCAM. In CPCF,
      the average volume of the individual needles in suspension was increased by 50%
      in microgravity compared to those in the ground control.

PMID- 12206162
TI  - Hans Goldmann: scholar, clinician, friend.

PMID- 12206163
TI  - Public fantasy and the logic of sacrifice in the Physician's tale.

PMID- 12206164
TI  - Completeness of India's sample registration system: an assessment using the
      general growth balance method.
AB  - In the preceding issue of this journal, a generalized version of the Brass growth
      balance method was proposed that made it applicable to populations that are not
      stable and are open to migration. In this companion paper, the results of
      applying this new procedure to data from India's Sample Registration system for
      the decades 1971-80 and 1981-90 are discussed. The results at the national level
      show that, during the decade 1981-90, 5 percent of the deaths among men, 12
      percent of the deaths among women, and about 7 percent of births were being
      missed by the system. Further, it is estimated that the level of under
      enumeration in the 1991 Census was more than that of the 1981 Census by 0.7
      percent for males and 1.4 percent for females. The paper also presents results
      for major Indian states.

PMID- 12206165
TI  - Infant feeding and post-neonatal mortality in Derbyshire, England, in the early
      twentieth century.
AB  - This paper examines influences on post-neonatal mortality in Derbyshire (England)
      in the early twentieth century, by applying multivariate hazard analysis to a
      rare individual-level data set. The data allow detailed patterns of breastfeeding
      and weaning to be examined. The role of feeding is given special attention as a
      mediator between mortality and the other environmental, social, and demographic
      factors considered. Twins and illegitimate children were more likely to have been
      hand-fed, but this could explain only a small fraction of their increased
      vulnerability. Artificial feeding was associated with increased risks of death
      from diseases was predominantly the result of the greater likelihood of
      congenitally weak children being hand-fed. Most of the variation in post-neonatal
      mortality, particularly from respiratory disease, was explained by environmental
      influences - population density, altitude, and the presence of mining.

PMID- 12206166
TI  - Continuity of women's work, breastfeeding, and fertility in Ghana in the 1980s.
AB  - Much of the inconsistency that has appeared in studies of the effect of women's
      work on fertility in less developed countries has been attributed to the varying
      accessibility of employment in the modern sector. The analysis presented in this
      paper shows that continuity of work matters more than sector of work. It also
      confirms that, even in a setting of low contraceptive prevalence, increased
      fecundity associated with the less intense breastfeeding practices of working
      women do not result in shorter birth intervals. The influence of women's work on
      fertility control is likely to be underestimated if the effects of sporadic
      versus continuous work are conflated, or if fecundity differentials by work
      status are unmeasured.

PMID- 12206167
TI  - Distinctive features of age-specific fertility profiles in the English-speaking
      world: common patterns in Australia, Canada, New Zealand and the United States,
      1970-98.
AB  - The paper seeks to identify common features in the fertility patterns of the
      English-speaking world and provide a model basis for comparison of fertility
      between countries and over time. Attention is focused on the heterogeneity within
      the fertility patterns of Australia, Canada, New Zealand, and the United States,
      similar to that reported earlier for the UK and the Irish Republic. The recent
      age-specific fertility patterns of these countries display a marked 'bulge' in
      fertility of women under age 25. A mixture model with two-component Hadwiger
      functions provides a suitable fit. The heterogeneity thus suggested is related to
      the proportion of births outside marriage. Additionally, there is some evidence
      that, in the United States, and lesser extent in New Zealand, this heterogeneity
      in fertility patterns may be explained by ethnic difference in the timing and
      number of births.

PMID- 12206168
TI  - Violations of service fairness and legal ramifications: the case of the managed
      care industry.
AB  - Adapted from Chan's (2000) model depicting success of litigation, this paper
      argues that with the application of various legislation, health maintenance
      organizations' (HMOs') violations of service fairness to each group: enrollees,
      physicians, and hospitals give rise to each group's lawsuits against the HMOs.
      Various authors (Bowen et al., 1999; Seiders and Berry, 1998) indicate that
      justice concepts such as distributive, procedural, and interactional justice can
      be applied to the area of service fairness. The violation of these underlying
      justice principles with HMOs' service unfairness to enrollees, physicians, and
      hospitals is examined. A general synopsis of the ethical issues in the managed
      care industry is provided. The various lawsuits launched by each group:
      enrollees, physicians, and hospitals together with the key statutes used are
      discussed. This paper also highlights the provisions and ramifications of the 11
      April 2000 landmark agreement that Aetna made with Texas Attorney General John
      Cornyn to settle the 1998 lawsuit brought against the company. Lastly, the
      current ethical issues in the managed care industry are further discussed. The
      value of this paper can be adapted to the study of organizations' service
      fairness violations in other industries or in the educational, governmental, and
      not-for-profit sectors both nationally and internationally.

PMID- 12206169
TI  - The effect of extreme cooling on globular and fibrillar proteins.
AB  - In connection with space research and the development of exobiology, it is of
      interest to study the influence of various physical conditions of some planets on
      biochemically significant substances at the organismal as well as the molecular
      level. From a series of investigations for the present communication, we have
      chosen data demonstrating the action of one of such factors, low and super low
      temperatures, on biomacromolecules in vitro.

PMID- 12206170
TI  - Life in the spacecraft and planetary station.
AB  - Further exploration of outer space and the solar system, performance of
      interplanetary flights and establishment of planetary stations necessitate
      extensive physiological studies and development of reliable life-support systems.
      When developing the systems, particular attention should be paid to the concept
      and testing of new processes which can provide a highly efficient regeneration of
      vitally important materials and decrease the weight of expendables. Of great
      significance is the establishment of optimal parameters of the environment for
      long-term manned spaceflights and selection of facilities securing them. The
      development of new life-support systems should be based on a thorough study of
      the particular environment, proper selection and physiological and hygienical
      evaluation of their components. Long duration space missions can be planned from
      studies on the effects of space flight factors upon the human body to reveal its
      variability limits under peculiar conditions of the spacecraft or planetary
      station.

PMID- 12206171
TI  - Man as the main component of the closed ecological system of the spacecraft or
      planetary station.
AB  - Current life-support systems of the spacecraft provide human requirements for
      food, water and oxygen only. Advanced life-support systems will involve man as
      their main component and will ensure completely his material and energy
      requirements. The design of individual components of such systems will assure
      their entire suitability and mutual control effects. Optimization of the
      performance of the crew and ecological system, on the basis of the information
      characterizing their function, demands efficient methods of collection and
      treatment of the information obtained through wireless recording of physiological
      parameters and their automatic treatment. Peculiarities of interplanetary
      missions and planetary stations make it necessary to conform the schedule of
      physiological recordings with the work-and-rest cycle of the space crew and
      inertness of components of the ecological system, especially of those responsible
      for oxygen regeneration. It is rational to model ecological systems and their
      components, taking into consideration the correction effect of the information on
      the health conditions and performance of the crewmen. Wide application of
      physiological data will allow the selection of optimal designs and sharply
      increase reliability of ecological systems.

PMID- 12206172
TI  - Experimental biological life support system. I. Continuous cultivation of algae
      as a link of a closed ecosystem.
AB  - According to the opinion of many researchers, a culture of microalgae may serve
      as a regenerator of atmosphere in the cabin of a spaceship. To use microalgae for
      these objectives, it was necessary to have an automatic unit possessing a high
      productivity of the cultivation process. This unit, containing a minimum of
      equipment, enables carrying on for an unlimited time the cultivation of algae
      without a drop in their productivity. The unit meeting these requirements (the
      cultivator) was developed by the authors and will be described in the
      presentation. The stability of the microalga photosynthetic system is
      characterized by the fact that after 70% biosynthesis repression by the
      ultraviolet radiation, a full regeneration of the productivity level takes place
      within 24 hours. In our experiments the system was functioning with the stable
      estimated productivity for many days (up to two months without interruption).
      During the process, no biological inhibitions to permanent performance and
      further prolongation of its life were found. As to the productivity, stability
      and control, the described biotechnological method may appear to be useful as a
      link of the closed ecosystem.

PMID- 12206173
TI  - Problem of reproduction of food protein by autotrophic organisms in
      extraterrestrial conditions.
AB  - To supply a man during his prolonged stay in extraterrestrial space with dietary
      protein by storing it in space vehicles seems to be impractical. Protein
      reproduction could be realized at present only by biosynthesis, which is possible
      with the autotrophic organisms and is the most economic, universal and therefore
      quite possible for use in life-support systems. In the paper, experimental
      results are presented on the biological value of single-celled algae proteins.
      The results obtained suggested that algae biomass in human rations could not be
      used in quantities needed for turnover of the components of the space-cabin
      atmosphere. The main obstacles lie in a hard broken algae shell, a large quantity
      of pigment, "allergization" of persons with biomass included in their rations,
      lack of some aminoacids in the protein, as well as man's psychological negativism
      to algae as a food product. Use of single-celled algae as a food source in the
      future will depend on improvement of its technological and biological management.
      A possible use of hydrogen-reducing bacteria as a biological dietary protein
      product is discussed.

PMID- 12206174
TI  - Correlation of dose rate and spectral measurements in the Inner Van Allen Belt.
AB  - Dose rate measurements and the charged particle environment of the Inner Van
      Allen Belt have been correlated using recent data obtained from the radiation
      research satellite, OV3-4. Six tissue equivalent ionization chambers, constructed
      of a material which simulates the muscle tissue response to ionizing radiation,
      measured the dose rate behind various types and thicknesses of material. The
      specific shields used for several of the chambers were 0.192 g/cm2 aluminum,
      0.797 g/cm2 Lucite and 4.485 g/cm2 brass. The proton and electron spectra were
      determined with an omnidirectional spectrometer using solid state detectors. The
      spectral measurements discussed here include geomagnetically trapped protons with
      energies in the range of 15 to 200 MeV. The proton spectra and dose rates are
      presented as profiles in terms of the McIlwain parameters of L (1.5, 2.0 and 2.5
      earth radii) and the magnetic field B (0.050 to 0.250 gauss). The excellent
      agreement between the measured dose rate and the theoretically predicted dose
      rate based on the measured spectra provides justification for the radiation
      transport techniques now being employed to predict the doses to be encountered
      during future manned space missions. It was found, however, that a more adequate
      description of the proton fluxes for energies greater than 50 MeV will be
      necessary to predict dose rate accurately behind shields of 2.5 g/cm2 thickness
      or greater.

PMID- 12206175
TI  - On the interrelations between ultraviolet and visible light during their
      simultaneous action on the cell.
AB  - Beyond the Earth's atmosphere, ultraviolet (UV) light that is a component of the
      Sun's spectrum appears as one of the limiting factors to life in space and on the
      planets which have no ozone layer in their atmosphere. At early stages in the
      evolution of life, the Earth's atmosphere contained neither free oxygen nor the
      layers serving as a screen for short-wave UV light. Under such conditions, the UV
      radiation lasted for 8-10 hours a day. Similar radiation conditions may be found
      on Mars. Still, we do not know to what extent the photo-reactivating region of
      sun radiation (3000-5490 angstroms) can protect cells from the action of short UV
      light. Therefore, it will be of interest to study a prolonged action of UV
      radiation on living systems (protozoa, bacteria, fungi, animal and plant cells)
      in the presence of visible rays capable of reactivating UV damage. We subjected
      infusoria (Paramecium caudatum) to prolonged action of UV light (2537 angstroms).
      The cells were irradiated daily for 8-16 hours with doses of 1.5-40 and 120 mkvt.
      A sharp reduction in the rate of division and the lethality to the infusoria were
      observed from the second to the fifth day of experimentation. In the light
      variant, UV radiation was performed simultaneously with the application of
      visible light (2800-15000 lux). In such conditions, the cells kept their normal
      rate of division for 12 days. In the next 30 days without irradiation, no
      deviation from the normal rate was noted. The experimental results permit the
      conclusion that under certain conditions of interaction between visible and UV
      light, UV does not produce a deleterious effect on cell division.

PMID- 12206176
TI  - Immune states in long-term space flights.
AB  - Maintenance of health, as contrasted to illness induced by infectious agents,
      reflects a tenuous balance between the host's resistance and the number and
      genetic characteristics of the infectious organisms present. Nature has evolved
      both nonspecific defense mechanisms and specific immune systems to protect the
      body against invasion by exogenous organisms or the numerous agents which may
      reside dormant within the host. Long-term space flights with their accompanying
      prolonged weightlessness, unaccustomed environmental factors, emotional
      disturbances, and unforeseen influences may alter the host's natural or specific
      immune states. The non-specific and specific host defenses will be discussed, and
      the particular effects which their alteration might have on provocation of latent
      viral infections will be considered. Viruses which classically may be induced to
      cause recurrent infections such as herpes simplex and herpes zoster will be
      described, but in addition the effect that altered host defenses might have on
      slow virus infections such as kuru and virus-induced malignancies will be
      emphasized.

PMID- 12206177
TI  - Microbiological and immunological aspects of extended manned space flights.
AB  - This paper is concerned with alterations in microbial flora and immunologic
      response of men during exposure to long-term confinement in a sealed cabin. The
      above changes depend on the environmental parameters, the duration of the
      exposure to different environmental factors, as well as on work rest schedules.
      An interchange of micro-organisms between subjects and activation of some species
      forming the normal human microflora took place in conditions of isolation. It was
      demonstrated that under these conditions some significant shifts in intestinal
      microflora occurred, including its general "simplification". It was found that
      the immunocompetent lymphoid tissue of the animals that had a simplified (reduced
      in number of species) intestinal microflora was significantly underdeveloped.
      Some ways of stimulating the immunocompetent systems of astronauts during long
      term space flights were considered. Special attention should be paid to the
      microbiological examination as part of the selection routine for future
      astronauts.

PMID- 12206178
TI  - Survival of bacterial spores under some simulated lunar surface conditions.
AB  - Spores of Bacillus subtilis were exposed to simulated lunar environmental
      factors, in order to estimate the chance of living matter to survive on the moon.
      Vacuum, radiation and extreme temperature were selected and their individual and
      combined influence was tested. High vacuum up to 2 x 10(-7) torr and ultra-high
      vacuum up to 5 x 10(-9) torr, ultraviolet rays (254 nm) and a temperature of 80
      degrees C were used. The results were compared with those of experiments on
      vegetative cells.

PMID- 12206179
TI  - Some potentialities of living organisms under simulated Martian conditions.
AB  - Temperature, humidity, pressure, composition of the atmosphere and radiation are
      the main factors conditioning life on the surface of Mars. When studying the
      Martian ecology, one must know the total effect of these factors. One may expect
      that, as a result of adaptation to low temperatures, there is a corresponding
      shift in the temperature optimum of enzymatic activity. Dryness is the main
      obstacle to active life. We suggest the presence of some soil moisture and water
      vapour. Moreover, there can be areas of permafrost. This minimum supply of water
      and periodic fluctuations of humidity may create conditions for the existence of
      drought-resistant organisms. Decreased atmospheric pressure alone does not affect
      micro-organisms, plants, protozoa and even insects. Ciliates reproduce in a
      flowing atmosphere of pure nitrogen containing 0.0002-0.0005% oxygen as an
      impurity. Protozoa may also develop in an atmosphere of 98-99% carbon dioxide
      mixed with 1% O2. Therefore, even traces of oxygen in the Martian atmosphere
      would be sufficient for aerobic unicellular organisms. Cells and organisms on
      earth have acquired various ways of protection from uv light, and therefore may
      increase their resistance further by adaptation or selection. The resistance of
      some organisms to ionizing radiation is high enough to enable them to endure hard
      ionizing radiation of the sun. Experiments with unicellular [correction of
      unicellar] organisms show that the effect of short wave uv radiation depends on
      the intensity of visible light, long-wave solar uv radiation, temperatures, cell
      repair processes, and the state of cell components, i.e. whether the cell was
      frozen, dried or hydrated.

PMID- 12206180
TI  - The influence of ultra-high vacuum on crystalline enzymes.
AB  - The exploration of physical conditions in space is closely related to the study
      of the influence of space factors on biological objects. The study of high vacuum
      is of particular importance because its effects are as yet imperfectly
      understood. Micro-organisms are suitable models for these investigations. It has
      already been found that in reference to high vacuum, micro-organisms may be
      divided into two groups: resistant and nonresistant forms. Bacterial and
      actinomycetal spores and conidia of Aspergillus are classified as the resistant
      forms. Parallel with these, rod-shaped non-sporeforming bacteria, yeasts and
      conidia of Penicillium, were found to be non-resistant forms. The mechanism of
      resistance and death of micro-organisms under high vacuum is still not clearly
      understood. Because of this the investigation employing such important
      macromolecules as crystalline cytochrome C, catalase, peroxidase and ATP have
      been carried out. These compounds were exposed to a high vacuum (10(-8)-10(-9) mm
      Hg) over a period of 72 hours. Then the weighed samples taken from treated
      specimens and controls were dissolved firstly in a phosphate buffer solution
      (pH=6.8-7.2) and were then diluted by this buffer up to a concentration of 10(-9)
      mg ml. The solutions obtained were investigated by the chemiluminescent method.
      It was found that high vacuum effects gave rise to a slight decrease (up 7%) in
      enzyme activity in concentrated solutions and to a significant inactivation (up
      to 30%) in diluted ones.

PMID- 12206181
TI  - Normalization of the immune status of the human body during prolonged space
      flight.
AB  - During long duration space flights a number of unfavourable situations arise due
      to changes in endogenous microflora and immunologic reactivity of men. It appears
      very important to develop procedures that can be used to normalize human
      resistance to infection. Methods of affecting protein synthesis in immune
      responsive cells are being investigated. It was found that ribonucleic acids
      stimulated antibody formation. Application of immunological, immunochemical, and
      isotopic methods confirmed that one of the main factors were ribonucleotides.
      Their effect is mainly to accelerate the proliferation of immunocompetent cells.
      Our experiments have shown that a single parenteral injection of a stimulant of
      such type is sufficient to sustain capacity for accelerated antibody formation
      for a long time. A search for non-specific stimulants is needed since they can be
      effectively used in cases of acute and subacute inhibition of immunity. Their use
      in combination with specific or non-specific activators may be required in
      chronic inhibition of immune reactions occurring, for instance, in qualitative
      and quantitative reduction of normal microflora. Our investigations have
      demonstrated that germ-free animals and animals with reduced microflora exhibit
      diminished regional lymphatic nodes, underdeveloped lymphoid tissue of Peyer's
      plaques and other changes. The paper discusses several methods of maintaining
      antigen balance.

PMID- 12206182
TI  - Gas exchange ("soil breathing") in the detection of extraterrestrial life.
AB  - The major exobiological problem is the detection of life on other planets. The
      present paper presents experimental data on gas exchange between different
      samples of terrestrial soils and the atmosphere. The feasibility of applying the
      gas chromatographic technique to the detection of extraterrestrial life is
      discussed.

PMID- 12206183
TI  - Shifts in the immunocompetence of lymphoid tissue in guinea pigs containing a
      limited microflora.
AB  - Many authors have demonstrated simplification of the species composition of the
      normal microflora in animals long kept in a closed environment. The purpose of
      the present work is to reveal the effect of such simplification (without
      reduction of the total number of bacteria) on the immunocompetent system of the
      animals. Three months old germ-free, monocontaminated (Staph. albus) and
      conventional guinea pigs with reduced fecal microflora were used in this study.
      Guinea pigs of the second group were fed a sterile diet but were kept in an
      ordinary vivarium. Two groups of control animals were: 1) conventionals fed
      regular diets; 2) conventionals fed the diet contaminated with fecal microflora
      of guinea pigs after sterilization. The fecal microflora was examined. The total
      number of bacteria in faeces of monocontaminated and microflora-reduced
      conventional animals was approximately the same as in conventional controls.
      Various lymphoid organs were examined. Their weight, size, number and activity of
      germinal centres, amount of globulin-producing cells, their differentiation and
      amount of globulins in single cells were determined. The lymphoid tissue in
      microflora-reduced animals and especially in monocontaminated guinea pigs was
      found to be underdeveloped. These changes were, however, less pronounced than in
      germ-free animals. It is suggested that simplification of the microflora in a
      macro-organism during long-term enclosure reduces the lymphoid tissue; such a
      macro-organism may develop severe reactions of the microbial shock, when
      occurring in a normal microbial environment.

PMID- 12206184
TI  - Resistance to infections in extended space flight.
AB  - Although much can be done to minimize the spread of micro-organisms from one
      individual to another, it is inevitable that an exchange of microflora will occur
      among individuals in an enclosed space. The chief sources of the microflora will
      be the respiratory tract, the gastrointestinal tract and the skin. Local care can
      deal with most problems of the skin, but potential problems in the respiratory
      and gastrointestinal tract cannot be dealt with as readily. Although many of the
      common pathogens can be eliminated by pre-flight procedures, the building up of
      normal flora represents potential hazards of substantial magnitude. The chief
      limitations of the effects of high concentrations of normal microbial flora are
      in the variety of host defensive mechanisms. Some of these have been reviewed,
      and it has been indicated that with respect to the bronchopulmonary defense
      mechanisms, the major defenses rest in the pulmonary alveolar macrophage system.
      This system has been shown to be adversely affected by a large variety of
      environmental circumstances, many of which will be operative in prolonged
      spaceflight. Similarly in the gastrointestinal tract, the large microbial load
      represents a source of micro-organisms and of waste products, which represent
      potential hazards. Methods for minimizing the latter effects include reducing the
      total microbial load or implanting a monoculture of a desired micro-organism
      which produces a minimum of the undesirable side effects. The solution to these
      problems requires sustained effort, and it is likely that solutions when found
      will have substantial application to medicine and public health in ground-based
      communities.

PMID- 12206185
TI  - Changes in the colicinogenic and hemolytic activities of Escherichia isolated
      from man during long-term confinement.
AB  - The paper presents data obtained during the year-long medico-engineering
      experiment (in which three test subjects participated) with respect to changes in
      the Escherichia composition as judged by colicinogenic and hemolytic activity. At
      the beginning of the experiment colicinogenic E. coli (col/D and col/B) was found
      in one of the three test subjects (U-85%); he also showed the highest stability
      of intestinal microflora throughout the experiment. The two other test subjects
      (B and M) displayed colicinogenic micro-organisms of the same type plus an
      unidentified type only during and immediately after emergency situations.
      Hemolytically active E. coli was isolated from the subjects with unstable
      microflora under emergency situations and at the end of the experiment. The
      results obtained allowed to note the periodicity in predominance of Escherichia
      with antagonistic and hemolytic activity as related to the changes in the
      physiological state of the macro-organism and the rate of mechanical and possibly
      genetic exchange within the microbial associations in the human intestine.

PMID- 12206186
TI  - The microflora of the human integument during prolonged confinement.
AB  - Under conditions of long-term isolation in a sealed environment the microbial
      contamination of the skin and upper respiratory tract of man was much more
      pronounced than under normal conditions. This intensification of the
      contamination went on in a series of periodic increases in the amount of micro
      organisms. Every such increase in micro-organisms was much more prominent than
      the preceding one. The harmful nature of the rise of the level of microbial
      contamination of human epidermal tissues was expressed by the development of
      bacterial population shifts and periodic increases in the number of pathogenic
      microbial forms.

PMID- 12206187
TI  - Bacterial contamination of confined, sealed space during long-term human
      occupation.
AB  - The long-term presence of human beings in a closed room of small volume is
      accompanied by the accumulation of a common and hemolytic microflora on their
      bodies, clothes, in the air, and on the room surfaces. A study was made of the
      dynamics of the spreading of such microflora in rooms measuring from 5-21 m3 when
      occupied by 1-3 persons for 5-30 days. With minimal sanitation the skin, after 30
      40 days, is covered with several thousands of microbes per cm2, of which the
      hemolytic staphylococci amount to about 500 cells per cm2. Linen contained tens
      of thousands of bacteria per cm2, including up to 7000 hemolytic staphylococci
      per cm2. Generally, air contamination increases during the experiment. The rate
      of increase depends on many factors, and includes, in addition to common
      microbes, hemolytic staphylococci, streptococci, including pathogenic ones. The
      distribution of microbes in the air depends on human activity, and the total
      number is lowered by improved sanitation. While initial surface contamination
      depends on preliminary disinfection, there is a steady accumulation of micro
      organisms on the chamber surfaces. No Escherichia coli could be found on chamber
      surfaces. Most bacteria were found on horizontal surfaces, working areas and
      floors (thousands of microbes per cm2), while ceilings and walls yielded from
      units to hundreds of cells per cm2.

PMID- 12206188
TI  - Microbiological problems of manned space flight.
AB  - The hazard of infectious disease in long-duration manned space flight is
      discussed in relation to the unique conditions of spacecraft environment.
      Confinement in a small, enclosed volume, special problems of waste disposal and
      personal hygiene, zero gravity, and high oxygen content present special features
      that favor transmission of micro-organisms. Alterations in microbial flora will
      occur and these will influence host defenses against disease. Genetic variants of
      micro-organisms could be induced by and selected under the unique conditions of
      space flight. A reduction in the variety of microbial flora could result in
      "microbial shock" on re-entry. The influence of environmental conditions of the
      spacecraft on host defenses against infection is unpredictable in the absence of
      investigative work. However, pre-flight assessment of immune status is
      recommended. A graduated pre-flight isolation period is highly recommended to
      permit exchange of flora, to protect astronauts from new agents, and to allow
      most infections to emerge.

PMID- 12206189
TI  - Theoretical and experimental decisions in the creation of an artificial ecosystem
      for human life support in space.
AB  - All of man's former space flights were not real ventures into space in the
      biological sense, as his life was supported with unregenerated earth supplies.
      The coming stage of space exploration requires man's long existence in the cosmos
      and on the other planets. This stage of man's activity outside the earth become
      possible only by creating small man-made ecosystems, permitting the support of
      his metabolism by the recycling of substances of the terrestrial biosphere.
      Creation of such systems is a new scientific and technical task. Man-made
      ecosystems are a new product of man's activity, which have no complete analogy,
      either in nature, or in technology. Stochastic mechanisms, which stabilize
      biogeocenosis, cannot be effective in small ecosystems. A technique of parametric
      control over biosynthesis made it possible to calculate, and put to practice, an
      ecosystem for man with a cyclic regeneration of the atmosphere, water and,
      partially, food. The specific bio-technological properties of small man-made
      ecosystems are being analysed. The possibility of their application for man's
      excursions into space and for the settlement of other planets is being
      considered.

PMID- 12206190
TI  - Brain and cognitive evolution: forms of modularity and functions of mind.
AB  - Genetic and neurobiological research is reviewed as related to controversy over
      the extent to which neocortical organization and associated cognitive functions
      are genetically constrained or emerge through patterns of developmental
      experience. An evolutionary framework that accommodates genetic constraint and
      experiential modification of brain organization and cognitive function is then
      proposed. The authors argue that 4 forms of modularity and 3 forms of neural and
      cognitive plasticity define the relation between genetic constraint and the
      influence of developmental experience. For humans, the result is the ontogenetic
      emergence of functional modules in the domains of folk psychology, folk biology,
      and folk physics. The authors present a taxonomy of these modules and review
      associated research relating to brain and cognitive plasticity in these domains.

PMID- 12206191
TI  - A cross-cultural analysis of the behavior of women and men: implications for the
      origins of sex differences.
AB  - This article evaluates theories of the origins of sex differences in human
      behavior. It reviews the cross-cultural evidence on the behavior of women and men
      in nonindustrial societies, especially the activities that contribute to the sex
      typed division of labor and patriarchy. To explain the cross-cultural findings,
      the authors consider social constructionism, evolutionary psychology, and their
      own biosocial theory. Supporting the biosocial analysis, sex differences derive
      from the interaction between the physical specialization of the sexes, especially
      female reproductive capacity, and the economic and social structural aspects of
      societies. This biosocial approach treats the psychological attributes of women
      and men as emergent given the evolved characteristics of the sexes, their
      developmental experiences, and their situated activity in society.

PMID- 12206192
TI  - Parental investment: how an equity motive can produce inequality.
AB  - The equity heuristic is a decision rule specifying that parents should attempt to
      subdivide resources more or less equally among their children. This investment
      rule coincides with the prescription from optimality models in economics and
      biology in cases in which expected future return for each offspring is equal. In
      this article, the authors present a counterintuitive implication of the equity
      heuristic: Whereas an equity motive produces a fair distribution at any given
      point in time, it yields a cumulative distribution of investments that is
      unequal. The authors test this analytical observation against evidence reported
      in studies exploring parental investment and show how the equity heuristic can
      provide an explanation of why the literature reports a diversity of birth order
      effects with respect to parental resource allocation.

PMID- 12206193
TI  - The association between psychopathology in fathers versus mothers and children's
      internalizing and externalizing behavior problems: a meta-analysis.
AB  - In light of the selective focus on maternal (vs. paternal) psychopathology as a
      risk factor for child development, this meta-analysis examines the relative
      strength of the association between psychopathology in mothers versus fathers and
      the presence of internalizing and externalizing disorders in children.
      Associations were stronger between maternal than paternal psychopathology and the
      presence of internalizing (but not externalizing) problems in children, with all
      average effect sizes being small in magnitude. Relations were moderated by
      variables that highlight theoretically relevant differences between
      psychopathology in mothers versus fathers (e.g., age of children studied, type of
      parental psychopathology) and by variables related to methodological differences
      across studies (e.g., method of assessing psychopathology in parents and
      children, type of sample recruited, familial composition).

PMID- 12206194
TI  - The effects of praise on children's intrinsic motivation: a review and synthesis.
AB  - The authors argue against a purely behavioral definition of praise as verbal
      reinforcement in favor of the view that praise may serve to undermine, enhance,
      or have no effect on children's intrinsic motivation, depending on a set of
      conceptual variables. Provided that praise is perceived as sincere, it is
      particularly beneficial to motivation when it encourages performance attributions
      to controllable causes, promotes autonomy, enhances competence without an
      overreliance on social comparisons, and conveys attainable standards and
      expectations. The motivational consequences of praise also can be moderated by
      characteristics of the recipient, such as age, gender, and culture.
      Methodological considerations, such as including appropriate control groups and
      measuring postfailure outcomes, are stressed, and directions for future research
      are highlighted.

PMID- 12206195
TI  - Translating emotion theory and research into preventive interventions.
AB  - Scientific advances in the field of emotions suggest a framework for
      conceptualizing the emotion-related aspects of prevention programs that aim to
      enhance children's socioemotional competence and prevent the emergence of
      behavior problems and psychopathology. A conception of emotions as inherently
      adaptive and motivational and the related empirical evidence from several
      disciplines and specialities suggest 7 principles for developing preventive
      interventions: the utilization of positive and negative emotions, emotion
      modulation as a mediator of emotion utilization, emotion patterns in states and
      traits, different processes of emotion activation, emotion communication in early
      life, and the development of connections for the modular and relatively
      independent emotions and cognitive systems. Each principle's practical
      implications and application in current prevention programs are discussed.

PMID- 12206196
TI  - Risk and maintenance factors for eating pathology: a meta-analytic review.
AB  - This meta-analytic review of prospective and experimental studies reveals that
      several accepted risk factors for eating pathology have not received empirical
      support (e.g., sexual abuse) or have received contradictory support (e.g..
      dieting). There was consistent support for less-accepted risk factors(e.g., thin
      ideal internalization) as well as emerging evidence for variables that potentiate
      and mitigate the effects of risk factors(e.g., social support) and factors that
      predict eating pathology maintenance(e.g., negative affect). In addition, certain
      multivariate etiologic and maintenance models received preliminary support.
      However, the predictive power of individual risk and maintenance factors was
      limited, suggesting it will be important to search for additional risk and
      maintenance factors, develop more comprehensive multivariate models, and address
      methodological limitations that attenuate effects.

PMID- 12206197
TI  - Critical Eotvos numbers for buoyancy-induced oil drop detachment based on shape
      analysis.
AB  - Critical values of the Eotvos number, which is half the Bond number, above which
      buoyancy induced drop detachment occurs, are estimated based on force balance
      equations available in the literature [Colloids Surf. A: Physicochem. Eng.
      Aspects 178 (2001) 249]. Since there are two significantly different expressions
      of the capillary retention force responsible for holding oil drops on a solid
      substrate in an aqueous phase, the critical dimensionless number is estimated
      with these two distinct equations. The differential equation defining the drop
      shape, with the constraints of the drop volume and the 'pinned' or 'receding'
      contact line, is numerically solved. The equilibrium drop shapes predicted are
      shown to match the experimentally observed variations in drop shape. From the
      numerical solution, it is observed that for interfacial tension (IFT) values
      lower than a certain limit for a given drop size, no numerically estimated drop
      shape can fulfil the drop volume constraint. Similarly, for the dimensionless
      number above a critical value, no shape can meet all the constraints. These
      critical Eotvos numbers are estimated, based on the above numerical approach, for
      initial contact angles measured in oil varying from 20 degrees to 90 degrees. It
      is found that the critical Eotvos numbers estimated from the numerical shape
      analysis are between the critical values estimated from the two force-balance
      equations. Near 90 degrees, the critical values estimated from the drop shape
      analysis matches the values from one of the force balance estimates, but merges
      with the critical values of the dimensionless number, estimated from the other
      force balance model near 10 degrees. From this analysis, it appears that a
      combination of the two equations for the capillary retention force is required,
      with one dominating when the contact angles are high, while the other applies for
      low values of the contact angle.

PMID- 12206198
TI  - Chirality, twist and structures of micellar lyotropic cholesteric liquid crystals
      in comparison to the properties of chiralic thermotropic phases.
AB  - Phase chirality in disk-like lyotropic cholesteric phases (Ch(D)) was
      investigated, which was induced by addition of center and axial chiral dopants to
      achiral lyotropic nematic host phases (N(D)). In a lyotropic nematic matrix of
      the disk-like N(D) phase in the ternary system hexadecyldimethylethyl ammonium
      bromide (C16Me2EABr)/water/n-decanol, a disk-like lyotropic cholesteric phase
      Ch(D) was induced by addition of the axial optically active compound R(-)-1,1'
      binaphthalene-2,2'-diyl-hydrogen-phosphate (BDP). The helical twisting power
      (HTP) of the BDP is generally lower than the HTP value of inducing substances
      with center chirality as cholesterol, prednisolone and taurocholic acid. At
      constant composition of the N(D) phase, the helix lengths were determined in
      dependence on the BDP and steroid concentration by means of evaluation of the
      'spaghetti-like' texture using polarizing microscopy. The reciprocal helix
      lengths are changing linearly with rising BDP concentration. The properties of
      the Ch(D) phase (textures, helix lengths, structural parameters of the micelles)
      induced by the chiral compounds and changed by the composition of host phases can
      give information to the mechanism of chirality transfer from the molecular level
      to that of the micellar aggregates and finally, to the liquid crystalline
      superstructure. Furthermore, the matrix influence of the N(D) phase on the helix
      formation was examined at constant BDP and steroid concentration. The structure
      in the Ch(D) phase was described in terms of micelle parameters. Finally, the
      inducing properties of a center chiral optically active compound such as
      cholesterol, prednisolone and taurocholic acid were compared with those of the
      axial chiral compound BDP. Last but not least, the situation of the theoretical
      and structural background for helix formation in liquid crystals, e.g. the
      explanation of chiralic transfer between micelles is analyzed and discussed. Two
      main conditions are necessary to build up the helix in the Ch(D) phase: the
      formation of H-bridges; and the existence of a specific chiralic interaction
      energy between neighboring micelles in the cholesteric superstructure.

PMID- 12206199
TI  - Analysis of different approaches for evaluation of surface energy of microbial
      cells by contact angle goniometry.
AB  - Microbial adhesion on solid substrate is important in various fields of science.
      Mineral-microbe interactions alter the surface chemistry of the minerals and the
      adhesion of the bacterial cells to mineral surface is a prerequisite in several
      biobeneficiation processes. Apart from the surface charge and hydrophobic or
      hydrophilic character of the bacterial cells, the surface energy is a very
      important parameter influencing their adhesion on solid surfaces. There were many
      thermodynamic approaches in the literature to evaluate the cells surface energy.
      Although contact angle measurements with different liquids with known surface
      tension forms the basis in the calculation of the value of surface energy of
      solids, the results are different depending on the approach followed. In the
      present study, the surface energy of 140 bacterial and seven yeast cell surfaces
      has been studied following Fowkes, Equation of state, Geometric mean and Lifshitz
      van der Waals acid-base (LW-AB) approaches. Two independent issues were addressed
      separately in our analysis. At first, the surface energy and the different
      components of the surface energy for microbial cells surface are examined.
      Secondly, the different approaches are evaluated for their internal consistency,
      similarities and dissimilarities. The Lifshitz-van der Waals component of surface
      energy for most of the microbial cells is realised to be approximately 40 mJ/m2
      +/-10%. Equation of state and Geometric mean approaches do not possess any
      internal consistency and yield different results. The internal consistency of the
      LW-AB approach could be checked only by varying the apolar liquid and it
      evaluates coherent surface energy parameters by doing so. The electron-donor
      surface energy component remains exactly the same with the change of apolar
      liquid. This parameter could differentiate between the Gram-positive and Gram
      negative bacterial cells. Gram-negative bacterial cells having higher electron
      donor parameter had lower nitrogen, oxygen and phosphorous content on their cell
      surfaces. Among the four approaches, LW-AB was found to give the most consistent
      results. This approach provides more detailed information about the microbial
      cell surface and the electron-donor parameter differentiates different type of
      cell surfaces.

PMID- 12206200
TI  - Simultaneous measurements of skin sea surface temperature and sea surface
      emissivity from a single thermal imagery.
AB  - A novel method, to our knowledge, to measure simultaneously the thermal
      emissivity and skin temperature of a sea surface has been developed. The proposed
      method uses an infrared image that includes a sea surface and a reference object
      located near the surface. By combining this image with sky radiation temperature,
      we retrieve both skin sea surface temperature and sea surface emissivity from the
      single infrared image. Because the method requires no knowledge of thermal
      radiative properties of actual sea surfaces, it can be used even for a
      contaminated sea surface whose emissivity is hard to determine theoretically,
      e.g., oil slicks or slicks produced by biological wastes. Experimental results
      demonstrate that the estimated emissivity agrees with the theoretical prediction
      and, also, the recovered temperature distribution of skin sea surface has no
      appreciable high-temperature area that is due to reflection of the reference
      object. The method allows the acquisition of match-up data of radiometric sea
      surface temperatures that precisely correspond to the satellite observable data.

PMID- 12206202
TI  - Ocean optics phase-function inverse equations.
AB  - Equations are obtained for determining the Legendre polynomial expansion
      coefficients of the phase function from angular or angular-spatial integrals of
      the radiance measured either in water or at the surface.

PMID- 12206201
TI  - Path-radiance correction by polarization observation of Sun glint glitter for
      remote measurements of tropospheric greenhouse gases.
AB  - High-accuracy remote measurement of greenhouse gases is hampered by contamination
      of the field of view by the path radiance of solar radiation scattered from
      clouds and aerosols. A method is proposed for eliminating the effect of path
      radiance by differentiating two components of polarized light. The polarization
      of path radiance is measured directly at the wave-number region of strong water
      vapor absorption. Using this measurement, we eliminate the components of path
      radiance involved in other bands, which are used for greenhouse gas measurements,
      by differentiating two components of the polarized light. It is shown that the
      effect of path radiance on retrieving the column amount of gases potentially can
      be reduced to below 0.1%.

PMID- 12206204
TI  - Suppression of afterpulsing in photomultipliers by gating the photocathode.
AB  - A number of gating schemes to minimize the long-term afterpulse signal in
      photomultipliers have been evaluated. Blocking the excitation pulse by gating the
      photocathode was found to reduce the gate-on afterpulse background by a factor of
      230 over that for nongated operation. This afterpulse or signal-induced
      background (SIB), which is particularly troublesome in stratospheric lidar
      measurements, appears as a weak exponentially decaying signal extending into the
      millisecond region after the photomultiplier tube (PMT) is exposed to an intense
      submicrosecond optical pulse. Photocathode gating is not feasible in PMTs with
      semitransparent bialkali photocathodes because of their slow gate response time,
      but is easily implemented in PMTs with opaque bialkali or semitransparent
      multialkali (S-20) photocathodes that can be gated with nanosecond response. In
      those PMTs with semitransparent bialkali photocathodes, a gated (adjacent) focus
      grid (if available) also produces a significant reduction in the SIB.

PMID- 12206203
TI  - Fast and accurate model of underwater scalar irradiance.
AB  - A spectral model of scalar irradiance with depth is applied to calculations of
      photosynthetically available radiation for a vertically homogeneous water column.
      The model runs more than 14,000 times faster than the full Hydrolight code, while
      it limits the percentage error to 2.20% and the maximum error to less than 4.78%.
      The distribution of incident sky radiance and the effects of a wind-roughened
      surface are integrated into this model. It can be applied to case 1 waters as
      well as to case 2 waters that happen to be gelbstoff rich, and the volume
      scattering phase function can be generated dynamically based on the backscatter
      fraction. This new model is both fast and accurate and is, therefore, suitable
      for use interactively in models of the oceanic system, such as biogeochemical
      models or the heat budget part of global circulation models. It can also be
      applied by use of remote-sensing data to improve light-field calculations as a
      function of depth, which is needed for the estimation of global ocean carbon
      production and the ocean heat budget.

PMID- 12206205
TI  - Applications of optical sensing for laser cutting and drilling.
AB  - Any reliable automated production system must include process control and
      monitoring techniques. Two laser processing techniques potentially lending
      themselves to automation are percussion drilling and cutting. For drilling we
      investigate the performance of a modification of a nonintrusive optical focus
      control system we previously developed for laser welding, which exploits the
      chromatic aberrations of the processing optics to determine focal error. We
      further developed this focus control system for closed-loop control of laser
      cutting. We show that an extension of the technique can detect deterioration in
      cut quality, and we describe practical trials carried out on different materials
      using both oxygen and nitrogen assist gas. We base our techniques on monitoring
      the light generated by the process, captured nonintrusively by the effector
      optics and processed remotely from the workpiece. We describe the relationship
      between the temporal and the chromatic modulation of the detected light and
      process quality and show how the information can be used as the basis of a
      process control system.

PMID- 12206206
TI  - Surface displacement imaging by interferometry with a light emitting diode.
AB  - We present an imaging technique to measure static surface displacements of
      electronic components. A device is supplied by a transient current that creates a
      variation of temperature, thus a surface displacement. To measure the latter, a
      setup that is based on a Michelson interferometer is used. To avoid the
      phenomenon of speckle and the drawbacks inherent to it, we use a light emitting
      diode as the light source for the interferometer. The detector is a visible CCD
      camera that analyzes the optical signal containing the information of surface
      displacement of the device. Combining images, we extract the amplitude of the
      surface displacement. Out-of-plane surface-displacement images of a
      thermoelectric device are presented.

PMID- 12206207
TI  - Application of a high-repetition-rate laser diagnostic system for single-cycle
      resolved imaging in internal combustion engines.
AB  - High-repetition-rate laser-induced fluorescence measurements of fuel and OH
      concentrations in internal combustion engines are demonstrated. Series of as many
      as eight fluorescence images, with a temporal resolution ranging from 10 micros
      to 1 ms, are acquired within one engine cycle. A multiple-laser system in
      combination with a multiple-CCD camera is used for cycle-resolved imaging in
      spark-ignition, direct-injection stratified-charge, and homogeneous-charge
      compression-ignition engines. The recorded data reveal unique information on
      cycle-to-cycle variations in fuel transport and combustion. Moreover, the imaging
      system in combination with a scanning mirror is used to perform instantaneous
      three-dimensional fuel-concentration measurements.

PMID- 12206208
TI  - Relationship between sensitivity and waveguide position on the diaphragm in
      integrated optic pressure sensors based on the elasto-optic effect.
AB  - The sensitivities of integrated optic pressure sensors with diaphragms
      theoretically are known to be strongly dependent on the position of the sensing
      waveguide on the diaphragm. According to the theoretical results, the diaphragm
      edge is the best position for the waveguide of a sensor based on the elasto-optic
      effect. The relationship between sensitivity and the waveguide position, however,
      has not been investigated experimentally, although it is important in the
      designing of such a sensor and in determining the misalignment tolerance of the
      sensing waveguide. In this study, this relationship in a glass-based integrated
      optic sensor by use of an intermodal interference was examined experimentally.

PMID- 12206209
TI  - Arc-shaped waveguide switch based on the third-order nonlinear effect.
AB  - A kind of arc-shaped all-optical waveguide switch is proposed for the first time,
      to the best of our knowledge, and the switching characteristics of it are
      investigated by means of the beam propagation method. The effects of saturation
      and loss on the characteristics of the switch are discussed.

PMID- 12206210
TI  - Rapidly tuning miniature transversely excited atmospheric-pressure CO2 laser.
AB  - An experimental study of a rapidly tuning miniature transversely excited
      atmospheric-pressure CO2 laser is reported. To rapidly shift laser wavelengths
      over selected transitions in the 9-11 microm wavelength region, we have utilized
      a high-frequency stepping motor and a diffraction grating. The laser is highly
      automated with a monolithic microprocessor controlled laser line selection. For
      the achievement of stable laser output, a system of laser excitation with a
      voltage of 10 kV, providing effective surface corona preionization and allowing
      one to work at various gas pressures, is utilized. Laser operation at 59 emission
      lines of the CO2 molecule rotational transition is obtained and at 51 lines, the
      pulse energy of laser radiation exceeds 30 mJ. The system can be tuned between
      two different rotational lines spanning the wavelength range from 9.2 to 10.8
      microm within 10 ms.

PMID- 12206211
TI  - Fabrication of a distributed-feedback dye laser with a grating structure in its
      plastic waveguide.
AB  - Two approaches of fabricating grating structures for waveguided plastic dye
      lasers are described and compared for lasing performance. Rhodamine6G-doped
      poly(methyl methacrylate) (PMMA) film on a PMMA substrate was used for the
      waveguide, and a distributed-feedback (DFB) laser operation with a single
      propagation mode was demonstrated. The performances of both types of permanent
      grating structured DFB dye laser were better than those of a DFB dye laser on a
      plain waveguide with a dynamic grating formed by the interference of two pump
      beams. Wide tuning range is expected by use of a multistripe DFB laser with
      different grating pitches.

PMID- 12206212
TI  - Simultaneous injection locking of couples of high-power broad-area lasers driven
      by a common current source.
AB  - We experimentally demonstrate the simultaneous injection locking of pairs of high
      power broad-area laser diodes in a 19-laser array driven by a common current
      source. Each pair is injection locked by use of a single-mode low-power
      semiconductor laser. The frequency and phase locking are verified bythe optical
      spectrum and the interference pattern between the injection-locked lasers. The
      influence of frequency detuning on the (simultaneous) injection behavior has been
      experimentally clarified. We validate a necessary condition for the injection
      locking of a broad-area laser array.

PMID- 12206213
TI  - Sellmeier and thermo-optic dispersion formulas for KTP.
AB  - KTP has been found to be phase matchable for type-2 second-harmonic generation of
      the third harmonics of the CO2 laser wavelengths at 9.2714 and 9.5525 microm at
      20.0 degrees C. The resulting angle and temperature-tuning data combined with the
      literature values of the Nd:YAG laser-pumped optical parametric oscillator were
      used to improve the Sellmeier equations and the thermo-optic dispersion formula
      that reproduce well the temperature-tuned 90 degree phase-matching conditions of
      the flux-grown crystals. Applications to quasi phase matching are presented.

PMID- 12206214
TI  - Characterization of angled tapered superluminescent LEDs.
AB  - We present a detailed analysis of the output beam of high-power edge-emitting
      angled tapered superluminescent LEDs (A-TSLEDs). A device model, including
      spontaneous and stimulated emission processes as well as the typical nonuniform
      carrier-density distribution due to current spreading and carrier diffusion, has
      been developed and used to interpret the experimentally obtained characteristics
      of inhouse-fabricated A-TSLEDs. The good match between measured and theoretical
      results indicates that the model reproduces the A-TSLED operation very
      satisfactorily and clearly explains the role of the collecting lens on the
      pronounced asymmetry of some of the measured optical intensity profiles.

PMID- 12206215
TI  - Neural network scheme for the retrieval of total ozone from Global Ozone
      Monitoring Experiment data.
AB  - A novel approach to retrieving total ozone columns from the ERS2 GOME (Global
      Ozone Monitoring Experiment) spectral data has been developed. With selected GOME
      wavelength regions, from clear and cloudy pixels alike plus orbital and
      instrument data as input, a feed-forward neural network was trained to determine
      total ozone in a one-step inverse retrieval procedure. To achieve this training,
      ground-based total ozone measurements from the World Ozone and Ultraviolet Data
      Center (WOUDC) for the years 1996-2000, supplemented with Dobson-corrected Total
      Ozone Mapping Spectrometer (TOMS) data to provide global coverage, were
      collocated with GOME ground pixels into a training data set. Validation of the
      neural-network-retrieved ozone values relative to independent ground stations
      yielded a rms error of better than 11 Dobson units. Comparisons performed on the
      basis of operationally available TOMS and GOME level-3 maps exhibit good
      agreement in general, with a latitude-dependent offset.

PMID- 12206216
TI  - Estimation of the total uncertainty of sky-radiance measurements in field
      experimental conditions: implications for the aerosol single-scattering albedo.
AB  - We compare the spectral sky radiance measured by three ground-based optical
      radiometers during the second Aerosol Characterization Experiment (ACE-2) to
      estimate the total uncertainty of the radiance in field experimental conditions.
      The propagation of this uncertainty on the column-integrated aerosol single
      scattering albedo omega0 at 868 nm is investigated. The radiance measurements are
      affected by a systematic gain uncertainty of less than 2% in the visible spectral
      region and within 6% in the near-IR region. Correcting the measured radiance by a
      systematic uncertainty reduces the dispersion of the omega0 from 0.07 to 0.03.
      Besides, the total relative uncertainty of the radiance measurements in field
      experimental conditions is within 4% at any wavelength. The corresponding
      uncertainty delta omega0 is 4% for an aerosol optical thickness of 0.2.

PMID- 12206217
TI  - Expanding the dynamic range of a lidar receiver by the method of dynode-signal
      collection.
AB  - A method of lidar data collection by simultaneous registration of signals from
      the anode and several dynodes of the photomultiplier is suggested. The dynamic
      range of the receiver has been extended as many as 5 orders of magnitude in the
      case of cloud sensing. The stable operation under strong background illumination
      is possible without losses in fine signal structure.

PMID- 12206218
TI  - Optimal method of linear regression in laser remote sensing.
AB  - Remote lidar sensing in the photon-counting mode is now the commonly accepted
      method for studying atmospheric processes in the lower and free atmosphere.
      However, when processing signals obtained from lidar measurements, investigators
      necessarily face the problem of achieving accuracy in reconstructing the
      atmospheric parameters despite the presence of inhomogeneous noise in the
      measured signals. We propose an optimal method of linear regression (OMLR) of
      signals. The accuracy of the the method for the reconstructed signal is
      estimated. An example of application of the OMLR to the reconstruction of the
      temperature profile from the data obtained with a Raman lidar at the Siberian
      Lidar Station of the Institute of Atmospheric Optics (Tomsk, Russia) is given.
      The proposed method is distinguished by simplicity of interpretation of the
      criteria used, based on careful adherence to statistical principles. This method
      is shown to be an efficient auxiliary tool for the processing of measured data.

PMID- 12206219
TI  - Photon-limited synthetic-aperture imaging for planet surface studies.
AB  - The carrier-to-noise ratio that results from phase-sensitive heterodyne detection
      in a photon-limited synthetic-aperture ladar (SAL) is developed, propagated
      through synthetic-aperture signal processing, and combined with speckle to give
      the signal-to-noise ratio of the resultant image. Carrier- and signal-to-noise
      ratios are defined in such a way as to be familiar to the optical imaging
      community. Design equations are presented to show that a 10-microm SAL in orbit
      around Mars can give centimeter-class resolution with reasonable laser power. SAL
      is harder to implement in the short-wave infrared and is probably not practical
      at visible wavelengths unless many separate images can be averaged. Some tutorial
      information on phase-sensitive heterodyne detection and on synthetic-aperture
      signal processing and image formation is provided.

PMID- 12206220
TI  - Implementing torsional-mode Doppler ladar.
AB  - Laguerre-Gaussian laser modes carry orbital angular momentum as a consequence of
      their helical-phase front screw dislocation. This torsional beam structure
      interacts with rotating targets, changing the orbital angular momentum (azimuthal
      Doppler) of the scattered beam because angular momentum is a conserved quantity.
      I show how to measure this change independently from the usual longitudinal
      momentum (normal Doppler shift) and derive the apropos coherent mixing
      efficiencies for monostatic, truncated Laguerre and Gaussian-mode ladar antenna
      patterns.

PMID- 12206221
TI  - Strain measurement in a concrete beam by use of the Brillouin-scattering-based
      distributed fiber sensor with single-mode fibers embedded in glass fiber
      reinforced polymer rods and bonded to steel reinforcing bars.
AB  - The strain measurement of a 1.65-m reinforced concrete beam by use of a
      distributed fiber strain sensor with a 50-cm spatial resolution and 5-cm readout
      resolution is reported. The strain-measurement accuracy is +/-15 microepsilon
      (microm/m) according to the system calibration in the laboratory environment with
      non-uniform-distributed strain and +/-5 microepsilon with uniform strain
      distribution. The strain distribution has been measured for one-point and two
      point loading patterns for optical fibers embedded in pultruded glass fiber
      reinforced polymer (GFRP) rods and those bonded to steel reinforcing bars. In the
      one-point loading case, the strain deviations are +/-7 and +/-15 microepsilon for
      fibers embedded in the GFRP rods and fibers bonded to steel reinforcing bars,
      respectively, whereas the strain deviation is +/-20 microepsilon for the two
      point loading case.

PMID- 12206222
TI  - Polarization opposition effect and second-order ray tracing.
AB  - I develop a second-order ray-tracing model of the light scattered by a cloud of
      randomly oriented facets having sizes much larger than the incident wavelength.
      My results suggest that both symmetric and asymmetric branches of the
      polarization opposition effect can be produced by the same mechanism responsible
      for the photometric opposition effect, i.e., constructive interference of light
      rays traversing reciprocal paths that is associated with coherent backscattering
      enhancement. The model provides a greatly simplified representation of the
      physical phenomena to isolate the two mechanisms that may be responsible for the
      effect. The shapes and positions of the two branches of the polarization
      opposition effect calculated with the model are consistent with observation, so
      the model may provide a rapid technique to characterize the optical and physical
      properties of a scattering system. I note, however, that the model is a gross
      simplification containing only two physical mechanisms, Fresnel reflections and
      coherent interference, and it is possible that it represents a nonphysical
      description of particles smaller than the wavelength or that other mechanisms
      contributing to the polarization opposition effect are not included.

PMID- 12206223
TI  - Forward scattering induced by water drops on a transmissive substrate.
AB  - In this study the scattering of radiation by condensation drops deposited on a
      single glass plate is dealt with. Experiments were carried out in the visible
      radiation range by means of a laboratory measuring unit as a function of three
      parameters, namely, the phase of the condensation process, the wavelength of the
      incident radiation, and the radiation incidence angle. The experiments indicated
      that during the condensation process a steady state in the scattering pattern of
      single glass occurred after a transition phase. Owing to the condensate, more
      than 80% of the transmitted visible radiation was scattered. The scattering
      slightly diminished with increasing wavelength, from 400 to 700 nm, and the
      asymmetry of the scattering pattern enlarged with increasing incidence angle of
      the radiation.

PMID- 12206224
TI  - Model for optical forward scattering by nonspherical raindrops.
AB  - We describe a numerical model for the interaction of light with large raindrops
      using realistic nonspherical drop shapes. We apply geometrical optics and a Monte
      Carlo technique to perform ray traces through the drops. We solve the problem of
      diffraction independently by approximating the drops with area-equivalent
      ellipsoids. Scattering patterns are obtained for different polarizations of the
      incident light. They exhibit varying degrees of asymmetry and depolarization that
      can be linked to the distortion and thus the size of the drops. The model is
      extended to give a simplified long-path integration.

PMID- 12206225
TI  - Variable pressure infrared diode laser spectroscopy: a new method for trace-gas
      monitoring.
AB  - A new method for measuring trace concentrations of atmospheric pollutants by
      infrared diode laser spectroscopy has been devised. This method relies on the
      increase of the signal as the pressure inside the cell increases, while the
      frequency of the diode is stabilized on the line, even if it is unresolved.
      Performances of this method were tested with N2O and with 1,3-butadiene. As an
      example of application, we measured the butadiene emitted by car exhausts.
      Sensitivity and rapidity of this method are equivalent to the usual scanning
      method in which the whole line is described, but this new method benefits from
      its simplicity and robustness.

PMID- 12206226
TI  - Compact 50-Hz terawatt Ti:sapphire laser for x-ray and nonlinear optical
      spectroscopy.
AB  - We report a high-repetition-rate, compact terawatt Ti:sapphire laser system. The
      oscillator produces an 82-MHz pulse train consisting of broad-bandwidth pulses of
      0.5-nJ/pulse energy and of 9-fs pulse duration. The spectrally shaped, lambda/4
      regenerative amplifier supports an 80-nm bandwidth. A single 50-Hz repetition
      rate pump laser pumps both the regenerative amplifier and a multiple-pass
      amplifier. The final output from this laser is a 50-Hz pulse train made from
      pulses of 53 mJ/pulse energy and of 24-fs pulse duration. For generating
      ultrafast x-ray pulses, 90% of the energy from the final output of a 28-mm
      diameter (1/e2) beam is focused onto an ultrafast x-ray wire target. The energy
      conversion efficiency from optical (800-nm central wavelength) to x-ray
      (characteristic lines of K(alpha) from Cu at 8 keV) pulses is estimated to be 7 x
      10(-5). This laser system can also generate a lower-peak-power, dual-pulse output
      that can excite, simultaneously and coherently, Raman modes within an adjustable
      bandwidth (up to 700 cm(-1)) and at a tunable central vibrational frequency.
      Preliminary results for the generation of dual-pulse output and ultrafast x rays
      are presented.

PMID- 12206227
TI  - Fluorescence diagnostics of oil pollution in coastal marine waters by use of
      artificial neural networks.
AB  - We discuss the problems with and the real possibilities of determining oil
      pollution in situ in coastal marine waters with fluorescence spectroscopy and of
      using artificial neural networks for data interpretation. In general, the
      fluorescence bands of oil and aquatic humic substance overlap. At oil
      concentrations in water from a few to tens of micrograms per liter, the intensity
      of oil fluorescence is considerably lower than that of humic substances at
      concentrations that typically are present in coastal waters. Therefore it is
      necessary to solve the problem of separating the small amount of oil fluorescence
      from the humic substance background in the spectrum. The problem is complicated
      because of possible interactions between the components and variations in the
      parameters of the fluorescence bands of humic substances and oil in water.
      Fluorescence spectra of seawater samples taken from coastal areas of the Black
      Sea, samples prepared in the laboratory, and numerically simulated spectra were
      processed with an artificial neural network. The results demonstrate the
      possibility of estimating oil concentrations with an accuracy of a few micrograms
      per liter in coastal waters also in cases in which the contribution from other
      organic compounds, primarily humic substances, to the fluorescence spectrum
      exceeds that of oil by 2 orders of magnitude and more.

PMID- 12206228
TI  - Cavity ringdown spectroscopy of thin films in the mid-infrared.
AB  - To demonstrate the potential of the cavity ringdown technique in mid-infrared
      spectroscopy of thin film samples, we measured absorption losses in a C60 film on
      a BaF2 substrate using a tunable optical parametric amplifier source. With a
      Brewster angle sample geometry, we achieved a fractional loss sensitivity as
      small as 1.3 x 10(-7) with 1.5 cm(-1) resolution, an improvement in sensitivity
      of 2 orders of magnitude compared to standard Fourier transform infrared methods.
      At an absorption sensitivity of 5 x 10(-7), spectra of several C60 overtone lines
      were recorded.

PMID- 12206229
TI  - Determination of refractive indices of quarter-wavelength Bragg reflectors by
      reflectance measurements in wavelength and angular domains.
AB  - We show that all the structural properties of periodic dielectric multilayers can
      be accurately determined by a combined measurement of the transmission as a
      function of the wavelength and of the reflection as a function of the angle of
      incidence when the wavelength of the incident light is fixed. This method is
      applied to determine the structural properties of two commercial dielectric
      mirrors, and the results obtained are compared with a measurement of the same
      structural parameters by use of another technique based on the more standard
      optical guiding method.

PMID- 12206230
TI  - Photothermal deflection studies of GaAs epitaxial layers.
AB  - Photothermal beam deflection studies were carried out with GaAs epitaxial double
      layers grown on semi-insulating GaAs substrates. The impurity densities in thin
      epitaxial layers were found to influence the effective thermal diffusivity of the
      entire structure.

PMID- 12206231
TI  - Single-shot generation of a sonogram by time gating of a spectrally decomposed
      ultrashort laser pulse.
AB  - An experimental technique for single-shot generation of the sonogram of an
      ultrashort laser pulse is demonstrated. The method is based on the time gating of
      a spectrally decomposed test signal, transferring its spectral phase into a
      spatial phase, and the spatial filtering of the signal to produce a sonogram. The
      technique is evaluated experimentally, producing sonograms for linearly and
      nonlinearly chirped femtosecond laser pulses. The single-shot technique permits
      reconstruction of ultrashort pulse complex amplitude profiles and is useful for
      showing the signal in real time.

PMID- 12206232
TI  - Microscopic time-resolved two-dimensional imaging with a femtosecond amplifying
      optical Kerr gate.
AB  - We demonstrate microscopic time-resolved two-dimensional (2D) imaging that is
      based on a femtosecond amplifying optical Kerr gate (fs-amp OKG). The
      contribution of the optical nonlinear effects to the transverse imaging
      performance and the limit of the transverse resolving power are investigated. The
      optical Kerr effect in the excited state with amplification, used in the fs-amp
      OKG, does not deteriorate the quality of the time-resolved image at transverse
      resolutions up to at least 5.5 microm. We obtain a femtosecond-time-resolved 2D
      image of a microscopic object with a transverse resolution of 1.7 microm.

PMID- 12206233
TI  - Perspective: Here's to Fisher, additive genetic variance, and the fundamental
      theorem of natural selection.
AB  - Fisher's fundamental theorem of natural selection, that the rate of change of
      fitness is given by the additive genetic variance of fitness, has generated much
      discussion since its appearance in 1930. Fisher tried to capture in the formula
      the change in population fitness attributable to changes of allele frequencies,
      when all else is not included. Lessard's formulation comes closest to Fisher's
      intention, as well as this can be judged. Additional terms can be added to
      account for other changes. The "theorem" as stated by Fisher is not exact, and
      therefore not a theorem, but it does encapsulate a great deal of evolutionary
      meaning in a simple statement. I also discuss the effectiveness of reproductive
      value weighting and the theorem in integrated form. Finally, an optimum
      principle, analogous to least action and Hamilton's principle in physics, is
      discussed.

PMID- 12206234
TI  - The population genetics of adaptation: the adaptation of DNA sequences.
AB  - I describe several patterns characterizing the genetics of adaptation at the DNA
      level. Following Gillespie (1983, 1984, 1991), I consider a population presently
      fixed for the ith best allele at a locus and study the sequential substitution of
      favorable mutations that results in fixation of the fittest DNA sequence locally
      available. Given a wild type sequence that is less than optimal, I derive the
      fitness rank of the next allele typically fixed by natural selection as well as
      the mean and variance of the jump in fitness that results when natural selection
      drives a substitution. Looking over the whole series of substitutions required to
      reach the best allele, I show that the mean fitness jumps occurring throughout an
      adaptive walk are constrained to a twofold window of values, assuming only that
      adaptation begins from a reasonably fit allele. I also show that the first
      substitution and the substitution of largest effect account for a large share of
      the total fitness increase during adaptation. I further show that the
      distribution of selection coefficients fixed throughout such an adaptive walk is
      exponential (ignoring mutations of small effect), a finding reminiscent of that
      seen in Fisher's geometric model of adaptation. Last, I show that adaptation by
      natural selection behaves in several respects as the average of two idealized
      forms of adaptation, perfect and random.

PMID- 12206235
TI  - Within- and between-population variation for Wolbachia-induced reproductive
      incompatibility in a haplodiploid mite.
AB  - Wolbachia pipientis is a bacterium that induces cytoplasmic incompatibility (CI),
      the phenomenon in which infected males are reproductively incompatible with
      uninfected females. CI spreads in a population of hosts because it reduces the
      fitness of uninfected females relative to infected females. CI encompasses two
      steps: modification (mod) of sperm of infected males and rescuing (resc) of these
      chromosomes by Wolbachia in the egg. Infections associated with CI have mod+
      resa+ phenotypes. However, mod- resc+ phenotypes also exist; these do not result
      in CI. Assuming mod/resc phenotypes are properties of the symbiont, theory
      predicts that mod- resc+ infections can only spread in a host population where a
      mod+ resc+ infection already occurs. A mod- resc+ infection spreads if the cost
      it imposes on the infected females is lower than the cost inflicted by the
      resident (mod+ resc+) infection. Furthermore, introduction of a mod- Wolbachia
      eventually drives infection to extinction. The uninfected population that results
      can be recolonized by a CI-causing Wolbachia. Here, we investigated whether
      variability for induction of CI was present in two Tetranychus urticae
      populations. In one population all isofemale lines tested were mod-. In the
      other, mod+ resc+ and mod- resc+ isofemale lines coexisted. We found no evidence
      for a cost difference to females expressing either type (mod-/-). Infections in
      the two populations could not be distinguished based on sequences of two
      Wolbachia genes. We consider the possibility that mod- is a host effect through a
      population dynamics model. A mod- host allele leads to infection extinction in
      the absence of fecundity differences. Furthermore, the uninfected population that
      results is immune to reestablishment of the (same) CI-causing Wolbachia.

PMID- 12206236
TI  - Local adaptation in the Linum marginale-Melampsora lini host-pathogen
      interaction.
AB  - The potential for local adaptation between pathogens and their hosts has
      generated strong theoretical and empirical interest with evidence both for and
      against local adaptation reported for a range of systems. We use the Linum
      marginale-Melampsora lini plant-pathogen system and a hierarchical spatial
      structure to investigate patterns of local adaptation within a metapopulation
      characterised by epidemic dynamics and frequent extinction of pathogen
      populations. Based on large sample sizes and comprehensive cross-inoculation
      trials, our analyses demonstrate strong local adaptation by Melampsora to its
      host populations, with this effect being greatest at regional scales, as
      predicted from the broader spatial scales at which M. lini disperses relative to
      L. marginale. However, there was no consistent trend for more distant pathogen
      populations to perform more poorly. Our results further show how the
      coevolutionary interaction between hosts and pathogens can be influenced by local
      structure such that resistant hosts select for generally virulent pathogens,
      while susceptible hosts select for more avirulent pathogens. Empirically, local
      adaptation has generally been tested in two contrasting ways: (1) pathogen
      performance on sympatric versus allopatric hosts; and (2) sympatric versus
      allopatric pathogens on a given host population. In situations where no host
      population is more resistant or susceptible than others when averaged across
      pathogen populations (and likewise, no pathogen population is more virulent or
      avirulent than others), results from these tests should generally be congruent.
      We argue that this is unlikely to be the case in the metapopulation situations
      that predominate in natural host-pathogen interactions, thus requiring tests that
      control simultaneously for variation in plant and pathogen populations.

PMID- 12206237
TI  - Age at maturity and diversification in woody angiosperms.
AB  - Angiosperm diversification has been associated with plant-animal interactions
      such as seed dispersal and pollination and life-history characters such as rapid
      growth and fast reproduction. This paper relates a life-history character (age at
      maturity) to woody angiosperm diversification. Here I present a comparative
      analysis of data drawn from the literature, indicating that time to first
      reproduction is shorter in woody angiosperms than in gymnosperms. In addition,
      age at maturity is negatively correlated with the rate of diversification
      (measured as the number of species per genus) at all the taxonomic levels
      analyzed and also when phylogenetically independent contrasts were conducted.
      This correlation suggests that early reproduction promotes diversification in
      woody angiosperms. Furthermore, this correlation is not a confounding effect of
      the association between age at maturity and other ecological factors that promote
      angiosperm diversification, such as pollination and seed dispersal systems.

PMID- 12206238
TI  - High male reproductive success of hermaphrodites in the androdioecious Phillyrea
      angustifolia.
AB  - Androdioecy, the coexistence of males and hermaphrodites within a population, is
      a rare breeding system, often considered as unlikely to evolve because of
      restrictive conditions for its maintenance. Phillyrea angustifolia, a wind
      pollinated shrub, is one of the handful species reported to be androdioecious.
      Our previous studies have shown that natural populations of this species in
      southern France exhibit higher male frequencies (approximately 50%) than
      predicted on theoretical grounds. Thus, the male functionality of hermaphrodites
      is still debated. To assess the functional breeding system of this species in the
      wild, a paternity analysis was performed with two highly polymorphic
      microsatellite loci on 729 seeds collected on 10 maternal shrubs in a natural
      population of 24 mature individuals of P. angustifolia. A large proportion of
      seeds were found to have been sired by pollen from outside the population.
      Analysis of seeds sired by individuals within the study population revealed a
      high male fertility of hermaphrodites resulting in a low male advantage in
      fertility for male plants. Intermate distances were found to have a strong impact
      on male reproductive success, whereas sexual morph had no effect, with males and
      hermaphrodites performing equivalently. This study is the first to unequivocally
      document the occurrence of a male function of hermaphrodites in a natural
      population of an androdioecious species.

PMID- 12206239
TI  - Gondwanan evolution of the grass alliance of families (Poales).
AB  - Phylogenetic interrelationships among all 18 families of Poales were assessed by
      cladistic analysis of chloroplast DNA rbcL and atpB sequences from 65 species.
      There are two well-supported main clades; the graminoid clade with Poaceae
      (grasses), Anarthriaceae, Centrolepidaceae, Ecdeiocoleaceae, Flagellariaceae,
      Joinvilleaceae, and Restionaceae; and the cyperoid clade with Cyperaceae,
      Juncaceae, and Thurniaceae. A sister group relationship between Poaceae and
      Ecdeiocoleaceae is identified with strong support. The sister group of this pair
      is Joinvilleaceae. These relationships help in elucidating the evolution of
      grasses and the grass spikelet. Dating of the tree was done by nonparametric rate
      smoothing of rbcL molecular evolution. Most Poales families date back to the
      Cretaceous >65 million years ago (mya). Dispersal-vicariance analysis indicates
      that the Poales originated in South America, the cyperoid clade in West Gondwana
      (South America or Africa), and the graminoid clade in East Gondwana (Australia).
      The Trans-Antarctic connection between South America and Australia, and its
      breakup about 35 mya, probably influenced the evolution of the Poales and the
      graminoid clade in particular, leading to vicariance between the continents, but
      the separation of Africa from the other Gondwanan areas, completed about 105 mya,
      is too old for such a relation.

PMID- 12206240
TI  - Genomes, multiple origins, and lineage recombination in the Glycine tomentella
      (Leguminosae) polyploid complex: histone H3-D gene sequences.
AB  - Relationships among the various diploid and polyploid taxa that comprise Glycine
      tomentella have been hypothesized from crossing studies, isozyme data, and repeat
      length variation for the 5S nuclear ribosomal gene loci. However, several key
      questions have persisted, and detailed phylogenetic evidence from homoeologous
      nuclear genes has been lacking. The histone H3-D locus is single copy in diploid
      Glycine species and has been used to elucidate relationships among diploid races
      of G. tomentella, providing a framework for testing genome origins in the
      polyploid complex. For all six G. tomentella polyploid races (T1-T6), alleles at
      two homoeologous histone H3-D loci were isolated and analyzed phylogenetically
      with alleles from diploid Glycine species, permitting the identification of all
      of the homoeologous genomes of the complex. Allele networks were constructed to
      subdivide groups of homoeologous alleles further, and two-locus genotypes were
      constructed using these allele classes. Results suggest that some races have more
      than one origin and that interfertility within races has led to lineage
      recombination. Most alleles in polyploids are identical or closely related to
      alleles in diploids, suggesting recency of polyploid origins and spread beyond
      Australia. These features parallel the other component of the Glycine subgenus
      Glycine polyploid complex, G. tabacina, one of whose races shares a diploid
      genome with a G. tomentella polyploid race.

PMID- 12206241
TI  - Phenotypic and allozyme variation in Mediterranean and desert populations of wild
      barley, Hordeum spontaneum Koch.
AB  - Populations of wild barley, Hordeum spontaneum Koch, were collected in two
      distinct climatic regions, desert and Mediterranean. Plants from five desert and
      five Mediterranean populations were compared and contrasted for extent and
      structure of phenotypic variation. These same 10 and one other population from
      each region were analyzed for allozyme variation. In a field trial of phenotypic
      diversity, two phenological and 14 morphological traits were examined. Study of
      allozyme variation was performed using eight enzyme systems encoding for 13 loci.
      Plants from the desert and Mediterranean regions were significantly different in
      seven of 16 phenotypic traits, exhibited a high (30%) interregional component of
      phenotypic variation, and showed a high degree of segregation on a principal
      component scattergram indicating ecotypic differentiation. Mediterranean
      populations were twice as variable as desert populations in reproductive growth
      parameters (stem and spike length) and grain filling (spikelet weight), but half
      as variable for onset of reproduction. The extent and structure of phenotypic and
      allozyme variation did not match. The Mediterranean and desert populations did
      not differ in amount of allozyme variation as estimated by mean number of alleles
      per locus, effective number of alleles, polymorphism, and gene diversity (n(a),
      n(e), P, and H(e)), did not segregate on the basis of population genetic
      distances, and exhibited a low proportion of interregion allozyme diversity (2%).
      No effect of selection on allozyme distribution was detected. Our results suggest
      that the adaptation of plants originating from desert and Mediterranean
      environments is reflected in phenotypic but not in allozyme variation.

PMID- 12206242
TI  - Evolution in the real world: stochastic variation and the determinants of fitness
      in Carlina vulgaris.
AB  - Empirical studies of life histories often ignore stochastic variation, despite
      theoretical demonstrations of its potential impact on life-history evolution.
      Here we use a novel approach to explore the effects of stochastic variation on
      life-history evolution and estimate the selection pressures operating on the
      monocarpic perennial Carlina vulgaris, in which flowering may be delayed by up to
      eight years. The approach is novel in that we use modern theoretical techniques
      to estimate selection pressures and the fitness landscape from a fully
      parameterised individual-based model. These approaches take into account temporal
      variation in demographic rates and density dependence. Analysis of 16 years' data
      revealed significant temporal variation in growth, mortality, and recruitment in
      our study population. Flowering was strongly size dependent and, unusually for
      such a species, also age dependent. Individual-based models of the flowering
      strategy, parameterized using field data, consistently underestimated the size at
      flowering, when temporal variation in demographic rates was ignored. In contrast,
      models that incorporated temporal variation in growth, mortality, and recruitment
      predicted sizes at flowering not significantly different from those observed in
      the field. Temporal variation in mortality, which had the largest effect on the
      flowering strategy, selected for increased size at flowering. An analytical
      approximation is presented to explain this result, extending the "1-year look
      ahead criterion" presented in Rees et al. (2000). A fitness landscape generated
      by following the fate of rare mutant invaders with a broad range of alternative
      flowering strategies demonstrated that the observed parameters were adaptive.
      However, the fitness landscape reveals that approximately equal fitness is
      achieved by a broad range of strategies, providing a mechanism for the
      maintenance of genetic variation. To understand how the different parameters that
      defined our models determine the fitness of rare mutants, we numerically
      estimated the elasticities and sensitivities of mutant fitness. This demonstrated
      strong selection on a number of the parameters. Elasticities and sensitivities
      estimated in constant and random environments were significantly positively
      correlated, and both were negatively related to the standard error of the
      parameter. This last result is surprising and, we argue, reflects the genetic and
      phenotypic responses to selection.

PMID- 12206243
TI  - Speciation in ancient cryptic species complexes: evidence from the molecular
      phylogeny of Brachionus plicatilis (Rotifera).
AB  - Continental lake-dwelling zooplanktonic organisms have long been considered
      cosmopolitan species with little geographic variation in spite of the isolation
      of their habitats. Evidence of morphological cohesiveness and high dispersal
      capabilities support this interpretation. However, this view has been challenged
      recently as many such species have been shown either to comprise cryptic species
      complexes or to exhibit marked population genetic differentiation and strong
      phylogeographic structuring at a regional scale. Here we investigate the
      molecular phylogeny of the cosmopolitan passively dispersing rotifer Brachionus
      plicatilis (Rotifera: Monogononta) species complex using nucleotide sequence
      variation from both nuclear (ribosomal internal transcribed spacer 1, ITS1) and
      mitochondrial (cytochrome c oxidase subunit I, COI) genes. Analysis of rotifer
      resting eggs from 27 salt lakes in the Iberian Peninsula plus lakes from four
      continents revealed nine genetically divergent lineages. The high level of
      sequence divergence, absence of hybridization, and extensive sympatry observed
      support the specific status of these lineages. Sequence divergence estimates
      indicate that the B. plicatilis complex began diversifying many millions of years
      ago, yet has showed relatively high levels of morphological stasis. We discuss
      these results in relation to the ecology and genetics of aquatic invertebrates
      possessing dispersive resting propagules and address the apparent contradiction
      between zooplanktonic population structure and their morphological stasis.

PMID- 12206244
TI  - The recruitment sweepstakes has many winners: genetic evidence from the sea
      urchin Strongylocentrotus purpuratus.
AB  - As a consequence of free spawning in the unpredictable nearshore environment,
      marine species with large fecundities and high pre-reproductive mortality may be
      subject to extreme variance in reproductive success. If the unpredictability of
      the ocean results in only a small subset of the adult population contributing to
      each larval cohort, then reproduction may be viewed as a sweepstakes, with chance
      events determining which adults are successful each spawning season. Such a
      reproductive sweepstakes scenario may partially account for large reductions in
      effective population sizes relative to census population sizes in marine species.
      We evaluated two predictions of the sweepstakes reproductive success hypothesis
      by testing: (1) whether sea urchin recruits contain reduced genetic variation
      relative to the adult population; and (2) whether cohorts of sea urchin recruits
      are genetically differentiated. Mitochondrial DNA sequences were collected from
      283 recently settled Strongylocentrotus purpuratus recruits from four annual
      cohorts spanning seven years in locations throughout California. Observed
      haplotype numbers and haplotype diversities showed little evidence of reduced
      genetic variation in the recruits relative to the diversity estimated from a
      previously reported sample of 145 S. purpuratus adults. Different cohorts of
      recruits were in some cases mildly differentiated from each other. A computer
      simulation of sweepstakes recruitment indicates that our sampling strategy had
      sufficient statistical power to detect large variances in reproductive success.

PMID- 12206245
TI  - Family-level covariation between parasite resistance and mating system in a
      hermaphroditic freshwater snail.
AB  - Genetic compatibility, nonspecific defenses, and environmental effects determine
      parasite resistance. Host mating system (selfing vs. outcrossing) should be
      important for parasite resistance because it determines the segregation of
      alleles at the resistance loci and because inbreeding depression may hamper
      immune defenses. Individuals of a mixed mating hermaphroditic freshwater snail,
      Lymnaea ovata, are commonly infected by a digenetic trematode parasite,
      Echinoparyphium recurvatum. We examined covariation between quantitative
      resistance to novel parasites and mating system by exposing snail families from
      four populations that differed by their inbreeding coefficients. We found that
      resistance was unrelated to inbreeding coefficient of the population, suggesting
      that the more inbred populations did not carry higher susceptibility load than
      the less inbred populations. Most of the variation in resistance was expressed
      among the families within the populations. In the population with the lowest
      inbreeding coefficient, resistance increased with outcrossing rate of the family,
      as predicted if selfing had led to inbreeding depression. In the other three
      populations with higher inbreeding coefficients, resistance was unrelated to
      outcrossing rate. The results suggest that in populations with higher inbreeding
      some of the genetic load has been purged, uncoupling the predicted relationship
      between outcrossing rate and resistance. Snail families also displayed crossing
      reaction norms for resistance when tested in two environments that presented low
      and high immune challenge, suggesting that genotype-by-environment interactions
      are important for parasite resistance.

PMID- 12206246
TI  - The Africanization of honeybees (Apis mellifera L.) of the Yucatan: a study of a
      massive hybridization event across time.
AB  - Until recently, African and European subspecies of the honeybee (Apis mellifera
      L.) had been geographically separated for around 10,000 years. However, human
      assisted introductions have caused the mixing of large populations of African and
      European subspecies in South and Central America, permitting an unprecedented
      opportunity to study a large-scale hybridization event using molecular analyses.
      We obtained reference populations from Europe, Africa, and South America and used
      these to provide baseline information for a microsatellite and mitochondrial
      analysis of the process of Africanization of the bees of the Yucatan Peninsula,
      Mexico. The genetic structure of the Yucatecan population has changed
      dramatically over time. The pre-Africanized Yucatecan population (1985) comprised
      bees that were most similar to samples from southeastern Europe and northern and
      western Europe. Three years after the arrival of Africanized bees (1989),
      substantial paternal gene flow had occurred from feral Africanized drones into
      the resident European population, but maternal gene flow from the invading
      Africanized population into the local population was negligible. However by 1998,
      there was a radical shift with both African nuclear alleles (65%) and African
      derived mitochondria (61%) dominating the genomes of domestic colonies. We
      suggest that although European mitochondria may eventually be driven to
      extinction in the feral population, stable introgression of European nuclear
      alleles has occurred.

PMID- 12206247
TI  - Host-associated genetic differentiation in the goldenrod elliptical-gall moth,
      Gnorimoschema gallaesolidaginis (Lepidoptera: Gelechiidae).
AB  - Careful study of apparently generalist phytophagous insects often reveals that
      they instead represent complexes of genetically differentiated host races or
      cryptic species. The goldenrod elliptical-gall moth, Gnorimoschema
      gallaesolidaginis, attacks two goldenrods in the Solidago canadensis complex: S.
      altissima and S. gigantea (Asteraceae). We tested for host-associated genetic
      differentiation in G. gallaesolidaginis via analysis of variation at 12 allozyme
      loci among larvae collected at six sites in Iowa, Minnesota, and Nebraska.
      Gnorimoschema gallaesolidaginis from each host are highly polymorphic (3.6-4.7
      alleles/locus and expected heterozygosity 0.28-0.38 within site-host
      combinations). Although there were no fixed differences between larvae from S.
      altissima and S. gigantea at any site, these represent well differentiated host
      forms, with 11 of 12 loci showing significantly different allele frequencies
      between host-associated collections at one or more sites. Host plant has a larger
      effect on genetic structure among populations than does location (Wright's FST =
      0.16 between host forms vs. F(ST) = 0.061 and 0.026 among altissima and gigantea
      populations, respectively). The estimated F(ST) between host forms suggests that
      the historical effective rate of gene flow has been low (N(e)m approximately
      1.3). Consistent with this historical estimate is the absence of detectable
      recombinant (hybrid and introgressant between host form) individuals in
      contemporary populations (none of 431 genotyped individuals). Upper 95%
      confidence limits for the frequency of recombinant individuals range from 5% to
      9%. Host association is tight, but imperfect, with only one likely example of a
      host mismatch (a larva galling the wrong host species). Our inferences about
      hybridization and host association are based on new maximum-likelihood methods
      for estimating frequencies of genealogical classes (in this case, two parental
      classes, F1 and F2 hybrids, and backcrosses) in a population and for assigning
      individuals to genealogical classes. We describe these new methods in the context
      of their application to genetic structure in G. gallaesolidaginis. Population
      phenograms are consistent with the origin of the host forms (at least in the
      midwestern United States) via a single host shift: altissima and gigantea moth
      populations form distinct lineages with 100% bootstrap support. Genetic structure
      in Gnorimoschema is of particular interest because another gallmaking insect
      attacking the same pair of hosts, the tephritid fly Eurosta solidaginis, includes
      a pair of host races with partial reproductive isolation. Gnorimoschema
      gallaesolidaginis and E. solidaginis therefore represent the first reported case
      of parallel host-associated differentiation, that is, differentiation by
      evolutionarily independent insect lineages across the same pair of host plants.

PMID- 12206248
TI  - The phylogeography of Amazonia revisited: new evidence from riodinid butterflies.
AB  - A fully resolved cladogram for 19 species in the Charis cleonus group of riodinid
      butterflies, which have closely parapatric ranges throughout the Amazon basin, is
      used to derive an area cladogram for the region. This represents the first
      comprehensive species-level analysis using insects and results in a hypothesis of
      Amazonian area relationships that is the most detailed to date. The Charis area
      cladogram is interpreted as supporting an historical vicariant split between the
      Guianas and the remainder of the Amazon and then between the upper and lower
      Amazon. The latter two clades can be further divided into the six most widely
      recognized areas of endemism and even smaller endemic centers within these, some
      of which, especially along the Madeira and lower Amazon Rivers, have never been
      previously hypothesized for butterflies. The overall pattern of historical
      interrelationships indicated is Guiana + ((Rondjnia + (Para + Belem)) + (Imeri +
      (Napo + Inambari))). The area relationships for riodinid butterflies show
      substantial congruence with those presented from the literature for amphibians,
      reptiles, birds, primates, rodents, and marsupials, suggesting a common vicariant
      history for these organisms. A summary area cladogram generated by combining area
      cladograms for all the aforementioned groups of organisms indicated the pattern
      of historical interrelationships to be (Guiana + (Rondjnia + (Para + Belem))) +
      (Imeri + (Napo + Inambari)). Charis cleonus group species distributions are
      noticeably larger around the upland periphery of Amazonia and smaller in the
      central and lower regions. A significant positive correlation between the
      proportion of range area above 100 m and total range size for each species is
      used to suggest that past sea-level rises may explain smaller range sizes in low
      lying regions and that riverine barriers have been important in shaping the
      current distribution of C. cleonus group species.

PMID- 12206250
TI  - Reconstructing the evolution of complex bird song in the oropendolas.
AB  - The elaborate songs of songbirds are frequent models for investigating the
      evolution of animal signals. However, few previous studies have attempted to
      reconstruct historical changes in song evolution using a phylogenetic comparative
      approach. In particular, no comparative studies of bird song have used a large
      number of vocal characters and a well-supported, independently derived phylogeny.
      We identified 32 features in the complex vocal displays of male oropendolas
      (genera Psarocolius, Gymnostinops, and Ocyalus) that are relatively invariant
      within taxa and mapped these characters onto a robust molecular phylogeny of the
      group. Our analysis revealed that many aspects of oropendola song are
      surprisingly evolutionarily conservative and thus are potentially useful
      characters for reconstructing historical patterns. Of the characters that varied
      among taxa, nearly two thirds (19 of 29) showed no evidence of evolutionary
      convergence or reversal when mapped onto the tree, which was reflected in a high
      overall consistency index (CI = 0.78) and retention index (RI = 0.88). Some
      reconstructed patterns provided evidence of selection on these signals. For
      example, rapid divergence of the songs of the Montezuma oropendola, Gymnostinops
      montezuma, from those of closely related taxa suggests the recent influence of
      strong sexual selection. In general, our results provide insights into the mode
      of vocal evolution in songbirds and suggest that complex vocalizations can
      provide information about phylogeny. Based on this evidence, we use song
      characters to estimate the phylogenetic affinities of three oropendola taxa for
      which molecular data are not yet available.

PMID- 12206249
TI  - Evidence for parallel ecological speciation in scincid lizards of the Eumeces
      skiltonianus species group (Squamata: Scincidae).
AB  - We identify instances of parallel morphological evolution in North American
      scincid lizards of the Eumeces skiltonianus species group and provide evidence
      that this system is consistent with a model of ecological speciation. The group
      consists of three putative species divided among two morphotypes, the small
      bodied and striped E. skiltonianus and E. lagunensis versus the large-bodied and
      typically uniform-colored E. gilberti. Members of the group pass through markedly
      similar phenotypic stages during early development, but differ with respect to
      where terminal morphology occurs along the developmental sequence. The
      morphotypes also differ in habitat preference, with the large-bodied gilberti
      form generally inhabiting lower elevations and drier environments than the
      smaller, striped morphs. We inferred the phylogenetic relationships of 53
      skiltonianus group populations using mtDNA sequence data from the ND4 protein
      coding gene and three flanking tRNAs (900 bp total). Sampling encompassed nearly
      the entire geographic range of the group, and all currently recognized species
      and subspecies were included. Our results provide strong evidence for parallel
      origins of three clades characterized by the gilberti morphotype, two of which
      are nested within the more geographically widespread E. skiltonianus. Eumeces
      lagunensis was also nested among populations of E. skiltonianus. Comparative
      analyses using independent contrasts show that evolutionary changes in body size
      are correlated with differences in adult color pattern. The independently derived
      association of gilberti morphology with warm, arid environments suggests that
      phenotypic divergence is the result of adaptation to contrasting selection
      regimes. We provide evidence that body size was likely the target of natural
      selection, and that divergences in color pattern and mate recognition are
      probable secondary consequences of evolving large body size.

PMID- 12206251
TI  - Hormonal manipulation of offspring number: maternal effort and reproductive
      costs.
AB  - We used exogenous gonadotropin hormones to physiologically enlarge litter size in
      the bank vole (Clethrionomys glareolus). This method allowed the study design to
      include possible production costs of reproduction and a trade-off between
      offspring number and body size at birth. Furthermore, progeny rearing and
      survival and postpartum survival of the females took place in outdoor enclosures
      to capture salient naturalistic effects that might be present during the fall and
      early winter. The aim of the study was to assess the effects of the manipulation
      on the growth and survival of the offspring and on the reproductive effort,
      survival, and future fecundity of the mothers. Mean offspring body size was
      smaller in enlarged litters compared to control litters at weaning, but the
      differences disappeared by the winter. Differences in litter sizes disappeared
      before weaning age due to higher mortality in enlarged litters. In addition to
      the effects of the litter size, offspring performance was probably also
      influenced by the ability of the mother to support the litter. Experimental
      females had higher reproductive effort at birth, and they also tended to have
      higher mortality during nursing. Combined effects of high reproductive effort at
      birth and high investment in nursing the litter entailed costs for the
      experimental females in terms of decreased probability of producing a second
      litter and a decreased body mass gain. Thus, enlarged litter size had both
      survival and fecundity costs for the mothers. Our results suggest that the
      evolution of litter size and reproductive effort is determined by reproductive
      costs for the mothers as well as by a trade-off between offspring number and
      quality.

PMID- 12206252
TI  - Sexual dimorphism in lizard body shape: the roles of sexual selection and
      fecundity selection.
AB  - Sexual dimorphism is widespread in lizards, with the most consistently dimorphic
      traits being head size (males have larger heads) and trunk length (the distance
      between the front and hind legs is greater in females). These dimorphisms have
      generally been interpreted as follows: (1) large heads in males evolve through
      male-male rivalry (sexual selection); and (2) larger interlimb lengths in females
      provide space for more eggs (fecundity selection). In an Australian lizard (the
      snow skink, Niveoscincus microlepidotus), we found no evidence for ongoing
      selection on head size. Trunk length, however, was under positive fecundity
      selection in females and under negative sexual selection in males. Thus,
      fecundity selection and sexual selection work in concert to drive the evolution
      of sexual dimorphism in trunk length in snow skinks.

PMID- 12206253
TI  - Direct application of keratinocyte growth factor, basic fibroblast growth factor
      and transforming growth factor-alpha during healing of tympanic membrane
      perforation in glucocorticoid-treated rats.
AB  - Peptide growth factors and cytokines modulate both normal and impaired wound
      healing. Topical application of growth factors in the form of ear drops may
      counteract impairment of wound healing in the tympanic membrane (TM). We applied
      keratinocyte growth factor (KGF), transforming growth factor (TGF)-alpha or basic
      fibroblast growth factor (bFGF) to the perforated TMs of rats in which healing
      impairment had been caused by systemic administration of a glucocorticoid.
      Histologic studies of the injured TM, including anti-5-bromo-2'-deoxyuridine
      immunohistochemistry, were performed on the third day after wounding. In the
      control ear, epidermal migration was markedly inhibited by glucocorticoid
      treatment and no hyperplasia was observed in any layer at the perforation edge.
      TMs treated with KGF showed marked hyperplasia in the epithelial layer at the
      perforation edge. In the bFGF- and TGF-alpha-treated groups, hyperplasia was
      observed in the epithelial and intermediate layers of the TM near the malleus
      handle and annulus, while no hyperplasia was seen in any layer at the perforation
      edge. Only KGF, therefore, improved epidermal migration in the TM, while all the
      growth factors tested induced hyperplasia in the TM.

PMID- 12206254
TI  - Correlations between virtual endoscopy and otoendoscopy of the retrotympanum.
AB  - The aim of this study was to examine the anatomical landmarks of the
      retrotympanum using two different techniques, virtual endoscopy (VE) and
      fiberoptic endoscopy, and to correlate the results furnished by the two methods.
      Ten otosclerotic patients who were due to undergo stapedectomy were scanned using
      high-resolution spiral CT. Selected CT datasets were processed with Navigator 2.0
      software to obtain virtual endoscopic views of the retrotympanum. Subsequently,
      during the surgical procedure, fiberoptic endoscopy was performed with 2.7-mm 0
      degrees and 30 degrees rigid endoscopes. The ability of the two imaging methods
      to identify specific anatomical structures was then compared. In all cases the
      pyramidal eminence, pyramidal crest and sinus tympani were clearly identified in
      both VE images and otoendoscopy recordings, while fiberoptic endoscopy seemed to
      be less satisfactory than VE for studying the facial sinus, sinus of Proctor and
      fossula of Grivot. The two techniques proved to be equally sensitive for
      visualizing the ponticulus and subiculum, while the stapedius tendon could be
      visualized only by means of fiberoptic endoscopy. Overall, VE imaging appears
      promising for rendering important anatomical details of the retrotympanum,
      allowing identification of osseous landmarks and exploring recesses that are
      difficult to visualize via otoendoscopy.

PMID- 12206255
TI  - Early structural tympanic membrane reactions to myringotomy: a study in an acute
      otitis media model.
AB  - Myringotomy (Myr) is one of the most frequently performed surgical procedures in
      children. However, events occurring in the early phases, i.e. a matter of hours,
      following Myr in the acute otitis media (AOM) model have not been described. The
      aim of the present study was to evaluate the early otomicroscopic and
      histopathologic reactions of the tympanic membrane (TM) after Myr during the
      course of AOM (AOM-Myr). The left tympanic bulla from 36 healthy Sprague-Dawley
      rats was inoculated with Streptococcus pneumoniae type 3. Forty-eight h later, at
      Day 0, 4 randomized animals were immediately sacrificed and the remaining animals
      were treated with bilateral Myr. Otomicroscopy and sacrifices were performed in
      series of 4 animals at 3, 6, 9, 12, 24 and 48 h, and 4 and 7 days. The AOM-Myr
      TMs were compared to non-infected Myr TMs (non-AOM-Myr). The TMs were then
      dissected free and routinely processed for light and electron microscopy. AOM
      developed in all inoculated ears at Day 0. In the pars tensa of the AOM-Myr TMs
      the reaction of the keratinocyte layer of the perforation border was already
      evident at 6 h. The lamina propria exhibited a strong inflammatory reaction,
      which became more organized from 12 h onwards. At Day 4 the perforations were
      closed in three-quarters of cases. At Day 7 all perforations were healed with a
      distorted scar. In the non-AOM Myr TMs a strong degranulation of mast cells and
      edema were found in the pars flaccida at 6 h. A keratin spur at the perforation
      border was not seen until 24 h. All perforations were patent on Day 7 and
      myringosclerotic deposits were abundant in these TMs. The infected TMs
      regenerated faster and closed their perforations at an earlier stage. These
      findings favor the hypothesis that there is a low risk of chronic perforations
      when myringotomizing AOM TMs.

PMID- 12206256
TI  - Suppression of epithelial ion transport transcripts during pneumococcal acute
      otitis media in the rat.
AB  - Until recently, it was not feasible to conduct genome-wide screening for gene
      transcript variations that play key roles in the pathogenesis of otitis media. In
      this study microarray technology was used to profile differential gene expression
      patterns from rat middle ear mucosa at 12 and 48 h after Streptococcus pneumoniae
      challenge. Real-time polymerase chain reaction was performed for independent
      verification of the microarray results. Three ion transport mRNAs were
      simultaneously suppressed more than 4-fold at 12 h in bacteria-challenged ears,
      including Na,K-ATPase alpha I subunit (SPATPa1), sodium channel beta 2 subunit
      (SCNB2) and sodium-hydrogen exchange protein isoform 2 subunit (NHE2). At 48 h
      after infection, the mRNA levels of SCNB2 and NHE2 had decreased 7- and 10-fold,
      respectively, whereas the relatively abundant SPATPa1 transcript showed recovery.
      The downregulation of Na(+)-transporting transcripts suggests a reduced number of
      epithelial cells and transporting proteins and/or the dysfunction of sodium
      transporters secondary to the bacterial infection. These changes can disrupt the
      coupling of the apical Na + entry and basolateral Na + extrusion, deplete the
      electrochemical Na+ transmembrane gradient, disrupt the intracellular osmotic
      equilibrium and lead to intracellular acidification and the accumulation of
      excess sodium, water and other organic and inorganic molecules in the middle ear
      cavity. Any or all of these changes may contribute to the initiation and
      persistence of middle ear mucosa inflammation and effusion during an episode of
      bacterial acute otitis media.

PMID- 12206257
TI  - Three-dimensional analysis of human locomotion in normal subjects and patients
      with vestibular deficiency.
AB  - The purpose of this study was to clarify the role of the vestibular system in
      human locomotion. The subjects were nine healthy controls, nine patients with
      unilateral vestibular deficiency (UVD) and nine patients with bilateral
      vestibular deficiency (BVD). The UVD subjects were Meniere's disease patients who
      were being treated with administration of gentamicin into the tympanic cavity.
      BVD subjects were hearing-impaired individuals who showed no response to the ice
      water caloric test. A total of 13 markers were attached to the head, trunk (C7),
      hip and foot in order to measure translational and rotational motions with the
      aid of a video image processing system. All subjects were instructed to restrict
      their stride length to approximately 80 cm while walking on a treadmill and
      watching a visual target. However, walking speed varied depending on the ability
      of the subject to maintain body equilibrium. The results showed that walking
      speed and step frequency were significantly lower for the UVD and BVD groups than
      for the normal group. Analysis of head movements in the sagittal plane showed a
      counteracting motion between pitch rotations and vertical translation as
      previously reported. We also found head counteracting motions between yaw
      rotation and lateral translation in the horizontal plane. These mechanisms are
      thought to help stabilize the gaze during walking. When the head fixation point
      was calculated by projecting the naso-occipital axis line during walking, the
      head counteracting motion was found to assist the vestibulo-ocular reflex in
      stabilizing the gaze. In addition, normal subjects seemed to use head
      stabilization as a space strategy in order to minimize head yaw movement. In
      contrast, UVD and BVD subjects adopted head stabilization as a trunk strategy.

PMID- 12206258
TI  - Cavernous haemangioma of the internal auditory canal.
AB  - Cavernous haemangioma is a rare neoplasm that can be easily misdiagnosed as
      acoustic neuroma when it occurs in the internal auditory canal (IAC) or cerebello
      pontine angle. A right cavernous haemangioma is reported in a 61-year-old male.
      The lesion was associated with non-pulsative tinnitus, deteriorating hearing loss
      and facial nerve dysfunction (House and Brackmann grade IV). A T1-weighted Gd
      diethylenetriaminepentaacetic acid-enhanced MRI scan demonstrated a small
      hyperintense lesion confined to the right IAC. The tumor was completely resected
      via a retrosigmoidal approach. Histologic examination demonstrated a vascular
      tumor composed of an irregular, dilated vascular space with collagenous walls
      lined by a vascular endothelium. Facial nerve function remained unchanged and the
      patient remained well with no evidence of recurrence 2 years after surgery. We
      conclude that progressive hearing loss associated with facial nerve dysfunction,
      particularly when the lesion in the IAC is small, should raise the possibility of
      cavernous haemangioma.

PMID- 12206259
TI  - Acoustic impedance study of peritubal myoclonus.
AB  - An audible clicking sound coexistent with the contractions of the peritubal
      muscles is thought to be an isolated form of palatal myoclonus that presents with
      myoclonal contractions of the soft palate, larynx, pharynx and, sometimes,
      cervicofacial area. Acoustic impedance measurements, by demonstrating the
      relation between the muscle contractions and the clicking noise, represent one of
      the ways in which the diagnosis can be confirmed. This paper reports the
      impedance changes following various maneuvers and simultaneous electromyography
      recordings in four patients with peritubal myoclonus and confirms the accuracy
      and simplicity of these tests. The pathology of peritubal myoclonus and its
      treatment options are discussed.

PMID- 12206260
TI  - Electromagnetic interference of bone-anchored hearing aids by cellular phones
      revisited.
AB  - The electromagnetic interference of the recently introduced bone-anchored hearing
      aid (BAHA) model "BAHA Compact" by digital cellular phones is investigated and
      compared with that of the older "BAHA Classic 300" model. Measurements with two
      different digital cellular phones in a laboratory setting indicated that the
      noise level due to electromagnetic interference was at least 10 dB lower for the
      BAHA Compact device than for the BAHA Classic 300. To compare the experience of
      patients using the BAHA Compact with those using a BAHA Classic 300 in an earlier
      study, a survey was performed. Six users of a BAHA Compact who used digital
      cellular phones participated in the survey. Four patients did not hear any noise
      associated with the use of a digital cellular phone. Two patients reported
      hearing quiet sounds when they were on the telephone, but not when somebody else
      in the vicinity used a digital cellular phone. These findings confirm that the
      susceptibility to electromagnetic interference of the BAHA Compact device is low.

PMID- 12206261
TI  - Functional roles of nasal nitric oxide in nasal patency and mucociliary function.
AB  - The purpose of this study was twofold: (i) to clarify whether it is possible to
      change the amount of nasal nitric oxide (NO) artificially; and (ii) to confirm
      that the artificially altered nasal NO has biological properties such as
      vasodilatation and mucociliary function. We measured nasal NO and nasal airway
      resistance (NAR) in healthy subjects before and after topical administration of
      sodium nitroprusside (SNP), an NO donor. We also measured nasal NO and saccharin
      transport time after administration of SNP or L-N(G)-nitroarginine methylester (L
      NAME), a NO synthase inhibitor. In addition, we examined the effect of SNP and L
      NAME on nasal NO and saccharin transport time after pretreatment with flutropium
      bromide (FB), an anticholinergic agent. Administration of SNP elicited increases
      in nasal NO and NAR in a dose-dependent manner. Nasal NO decreased significantly
      after topical administration of L-NAME. Saccharin transport time, an indicator of
      mucociliary function, was shortened after topical administration of SNP and
      prolonged after administration of L-NAME. Moreover, these phenomena were observed
      even after pretreatment with FB. These results suggest that artificially altered
      nasal NO may affect NAR and mucociliary function.

PMID- 12206263
TI  - Z-pharyngoplasty for sleep disorder and rhonchopathy.
AB  - We developed an operation that leaves the uvula intact and opens the pharynx by
      creating a Z-shaped incision in the palate, a procedure known as a Z
      pharyngoplasty (ZPP). Twenty-four patients were studied before and after ZPPs.
      None of the patients complained of symptoms after the procedure. In terms of
      subjective changes, 79% of patients felt that they could breathe better after
      ZPPs and 75% felt that they had slept well upon waking. In terms of differences
      noted by sleep monitoring, the minimum oxygen saturation (SaO2) level increased
      significantly (p = 0.0025), the number of hours of sleep during which SaO2 was >
      95% increased significantly (p = 0.0345), the apnea index decreased significantly
      (p = 0.0316), snoring decreased (p = 0.0637) and pulse rate decreased
      significantly (p = 0.0144) after ZPP.

PMID- 12206262
TI  - A decrease in maxillary sinus pressure, as seen in upper airway allergy or
      infection, results in an increase in upper airway nitric oxide levels.
AB  - The paranasal sinuses are connected to the nasal cavity via small osties. Ostial
      occlusion, caused by mucosal swelling, will result in a slowly increasing
      negative pressure inside the sinus cavity. In parallel, the oxygen content in the
      sinus will decrease, resulting in the development of relative hypoxia. Hypoxia is
      a powerful inducer of nitric oxide (NO) synthase, and inducible NO synthase has
      been shown to be present in considerable amounts in the upper airways, including
      the sinuses. The present study was designed to investigate whether a reduction in
      sinus pressure would affect upper airway NO production. Thirteen healthy
      volunteers were investigated. A pressure chamber was used to lower the ambient
      pressure to -4.9 kPa. NO was sampled from one nostril or via a drainage tube
      inserted into the maxillary sinus before, during and after the hypobaric
      exposure. When the pressure was decreased, NO levels increased from 256 +/- 15 to
      316 +/- 19 ppb (n = 13, p < 0.001). The NO levels remained elevated (282 +/- 21
      ppb; p < 0.05) when measurements were repeated 20 min after leaving the chamber.
      The nasal airway resistance (V2tot) also increased as a result of the chamber
      session (from 16 +/- 2 degrees before to 21 +/- 3 degrees after; p < 0.05). An
      increase in NO levels was also found when the experiments were repeated with NO
      sampled directly from the maxillary sinus (225 +/- 6 before and 265 +/- 9 ppb
      after; n = 6, p < 0.001). For control purposes the nasal analyses were repeated
      again, this time under hyperbaric conditions (+ 4.9 kPa). This resulted in a
      slight decrease in the NO levels (from 273 +/- 22 to 241 +/- 17 ppb; n = 10, p <
      0.001), but there was no change in the nasal airway resistance. We conclude that
      a reduction in sinus pressure, as seen in upper airway allergy or infection, may
      result in an increase in upper airway NO production.

PMID- 12206264
TI  - Tongue base reduction with temperature-controlled radiofrequency volumetric
      tissue reduction for treatment of obstructive sleep apnea syndrome.
AB  - In recent years a considerable effort has been made to establish the use of
      different surgical techniques for the treatment of obstructive sleep apnea
      syndrome (OSAS). Nevertheless, treatment of hypopharyngeal obstruction due to
      tongue base hypertrophy remains in many ways an unsolved problem. The aim of this
      study was to evaluate the safety and efficacy of tongue base reduction with
      temperature-controlled radiofrequency volumetric tissue reduction in the
      treatment of OSAS. Twenty patients with OSAS and tongue base hypertrophy were
      treated with radiofrequency tissue ablation. An intensified treatment protocol
      was used, delivering 2,800 J per treatment session under local anesthesia. Two
      nights of polysomnography testing were performed before and after treatment.
      Daytime sleepiness, snoring and postoperative morbidity were assessed using
      questionnaires. Mean respiratory disturbance index (RDI) was reduced from 32.1 to
      24.9/h after a mean of 3.4 treatment sessions. Six patients (33%) were cured
      after the procedure (reduction in RDI of > or = 50% and a postoperative RDI of <
      15/h) and ten (55%) showed an improvement of > 20% in their RDI. Daytime
      sleepiness and snoring improved significantly. Peri- and postoperative morbidity
      was low; one severe complication occurred (tongue base abscess). We were able to
      achieve similar cure and responder rates to those reported in a recently
      published pilot study but with a reduced number of treatment sessions. We believe
      that this technique may improve patient acceptance and have beneficial cost
      implications.

PMID- 12206265
TI  - Use of freeze-dried autologous fascia to augment the vocal fold: an experimental
      study in dogs.
AB  - This study assessed the practicality of using autologous freeze-dried fascia to
      augment the vocal fold. Freeze-dried autologous fascia was injected into the
      vocal fold and skin of dogs in order to monitor sequential histological changes.
      Fascia lata was harvested from six adult dogs. After freeze-drying, minced fascia
      suspended in hyaluronic acid was injected subcutaneously into the abdominal wall
      and directly into the vocal fold. The specimens were extracted 3 weeks after
      injection and studied histologically. Freeze-drying destroyed all cellular
      components but did not affect the collagen fibers, which are the major components
      of fascia. There was no evidence of degeneration, necrosis or infection.
      Fibroblastic infiltration was seen in the fascia injected into the vocal fold,
      but the fascia remained as an unencapsulated mass at the site of injection. This
      study demonstrates that freeze-drying does not compromise the collagen in fascia
      and that the injection of freeze-dried collagen is well tolerated. Freeze-dried
      fascia is a promising new augmentation material.

PMID- 12206266
TI  - Tissue engineering of human salivary gland organoids.
AB  - Radiation therapy for malignant head and neck tumours is mainly responsible for
      inadvertent damage of the salivary glands. Xerostomia is the major symptom of
      this condition, with consequent mucositis, dental caries, dysphagia and
      nutritional deficits. At present there is no routine treatment for radiation
      induced salivary dysfunction. Based on the principles of tissue engineering, this
      study presents a new experimental concept for reconstituting salivary gland
      function after radiation therapy for head and neck cancer. Human parotid cells
      were cultured with two different types of commercially available microcarriers
      Cytodex 3 and Cytopore 1-for up to 3 weeks in vitro. Cultures were controlled
      daily by means of inverted microscopy. Medium samples were tested for alpha
      amylase, tissue polypeptide antigen (TPA) and S100 in order to control parotid
      cell function in vitro. The vitality of the cells was investigated by in vitro
      staining with erythrosine. Immunocytochemical analysis for amylase and
      cytokeratin was performed in order to confirm epithelial character and maintain
      acinar cell type. Parotid gland cells could be cultured in a differentiated and
      vital state on both types of microcarriers for up to 3 weeks. Almost all of the
      cultured cells exhibited immunoreactivity for cytokeratin. High concentrations of
      TPA, a specific marker for salivary duct epithelium, indicated persistent
      differentiation of this cell type in vitro. Positivity for amylase was detectable
      in 20-45%, of cells growing on the microcarriers, and especially on Cytodex 3.
      Decreasing amylase levels in the culture medium indicated functional deficiencies
      of the remaining acinar cells. Tissue engineering of human salivary gland
      organoids on microcarriers is a new approach for potential causative treatment of
      radiation-induced xerostomia. Before clinical application can be considered
      significant improvements in the in vitro cultivation of salivary gland tissue and
      scaffold design have to be realized.

PMID- 12206267
TI  - Tumor-associated antigens as possible targets for immune therapy in head and neck
      cancer: comparative mRNA expression analysis of RAGE and GAGE genes.
AB  - Specific immune therapy targeting residual areas of cancer cells may emerge as a
      powerful treatment strategy for head and neck squamous cell carcinoma (HNSCC). In
      order to define possible targets for immune therapy, we evaluated the frequency
      of two groups of tumor antigens-the RAGE and GAGE families-by means of reverse
      transcriptase polymerase chain reaction using primary HNSCCs (n = 28), mucosa
      specimens as normal controls (n = 10) and HNSCC cell lines (n = 6). By means of
      specific primer selection we could differentiate between RAGE-1, -2, -3 and -4,
      as well as between two groups of GAGE genes (GAGE-1,2,7 vs GAGE-3,4,5,6,8). While
      all mucosa tissues (from smokers and non-smokers) were negative for both antigen
      families, 24/28 investigated tumors were positive for up to 5 tumor antigens.
      Among the RAGE genes, RAGE-1-positive tumors were the most abundant (8/28),
      followed by RAGE-2 (7/28) and RAGE-4 (6/28). Differences in the locations of
      HNSCCs were reflected by different RAGE family members being expressed most
      frequently: larynx, RAGE-1; oropharynx, RAGE-2; and hypopharynx, RAGE-4. Primers
      against GAGE-1,2,7 and GAGE-3,4,5,6,8 revealed 6/27 and 16/27 positive tumors,
      respectively. This report suggests that RAGE genes and GAGE-3,4,5,6,8 may be
      promising candidates for specific immune therapy in HNSCC.

PMID- 12206269
TI  - Retropharyngeal lymph node metastasis from cancer of the head and neck.

PMID- 12206268
TI  - The use and misuse of level IA dissection for head and neck cancer.

PMID- 12206270
TI  - Carotid resection and reconstruction for locally advanced head and neck tumors.
AB  - Head and neck surgeons hesitate to resect the carotid artery because of the
      postoperative risk of neurologic sequelae. However, there is no curative
      therapeutic option for head and neck neoplasms involving the carotid artery, with
      the exception of complete tumor removal. To evaluate the benefits and risks of
      carotid revascularization techniques in locally advanced head and neck tumors we
      performed a retrospective analysis in an institutional, tertiary care medical
      center. Seven patients (5 males, 2 females) with a median age of 58 years
      underwent en bloc removal of locally advanced head and neck tumors, including
      carotid resection and revascularization, in the University of Vienna General
      Hospital, over a 15-year period. In six patients carotid reconstruction was
      accomplished by bypass grafting (five autologous grafts, one synthetic graft) and
      in one patient angiopatchplasty was used. There were no perioperative neurologic
      complications or deaths. Survival was > 12 months in 5/7 patients; the other 2
      patients died within 6 months due to untractable progression of cancer. We
      conclude that carotid revascularization techniques offer the possibility of
      better local control for advanced head and neck tumors without additional risks
      of neuromorbidity or mortality.

PMID- 12206271
TI  - Headache as an unusual presenting symptom of retropharyngeal ganglioneuroma.
AB  - Ganglioneuromas are rare benign neurogenous neoplasms. The clinical symptoms of
      ganglioneuromas of the neck are usually mild and non-specific and definitive
      diagnosis requires a histological examination. We present the case of a 35-year
      old female who complained of retroauricular pain as her first symptom and who was
      initially diagnosed with migraine. ENT examination revealed a bulging of the left
      pharyngeal wall. Fine-needle aspiration biopsy was misleading in terms of
      diagnosis. Histology after extirpation showed a ganglioneuroma. Ganglion cell
      differentiation was proven using the new intermediate filament class alpha
      internexin immunohistochemical staining technique. Headache is an
      uncharacteristic symptom of ganglioneuroma and an interdisciplinary approach is
      required to find a possible cause. Periauricular pain without abnormal otoscopic
      findings should lead the otorhinolaryngologist to consider a retropharyngeal
      condition, especially if combined with dysphagia. Complete resection of the tumor
      using modern microsurgical techniques is the best way to extract ganglioneuroma
      today.

PMID- 12206272
TI  - Cervical metastasis of unknown origin: a series of 72 patients.
AB  - Cervical metastasis of unknown origin is still a challenging problem because of
      its relatively poor prognosis and the uncertainty regarding the primary site. We
      analyzed retrospectively all 72 patients with cervical metastases of unknown
      origin, diagnosed and treated between 1985 and 1995 in the five university
      hospitals of Finland in order to analyze survival rates and some prognostic and
      clinical factors of the disease. The most common sites where the primary tumor
      was found during follow-up or at autopsy were the lung (8%), the oral and
      pharyngeal region (7%) and the skin (6%). When the lower neck nodes (regions IV
      VI) were affected, the primary tumor was significantly (p < 0.001) more often
      found from the subclavicular sites. The disease-specific 5-year survival rate was
      32%. In multivariate analysis, nodal stage N2c or N3 [adjusted relative hazard of
      death (HR) 2.43], other metastases found at the time of treatment (HR 2.15) and
      age > 65 years (HR 2.12) were significantly associated with a poor prognosis.
      Median survival tended to be longer for patients treated with surgery combined
      with radiotherapy (39.9 months) compared with those treated with radiotherapy
      alone (16.8 months), but this difference was not statistically significant (p =
      0.153).

PMID- 12206273
TI  - Re: Extensive interstital collagen...by Sanai et al.

PMID- 12206274
TI  - Thinking styles and modes of thinking: implications for education and research.
AB  - The author investigated the relationship of thinking styles to modes of thinking.
      Participants were 371 freshmen (aged 18 and 19) from the University of Hong Kong.
      Participants responded to the Thinking Styles Inventory (R. J. Sternnberg & R. K.
      Wagner, 1992) and the Style of Learning and Thinking (Youth Form; E. P. Torrance,
      B. McCarthy, & M. T. Kolesinski, 1988). A major finding was that creativity
      generating and complex thinking styles were significantly positively correlated
      with the holistic mode of thinking but significantly negatively correlated with
      the analytic mode of thinking. Thinking styles that denote the tendency to norm
      favoring and simplistic information processing were significantly positively
      correlated with the analytic mode of thinking and significantly negatively
      correlated with the holistic mode of thinking. In a preliminary conclusion, it
      appears that the thinking style construct overlaps the mode of thinking
      construct. Implications of this finding for teachers and researchers are
      delineated.

PMID- 12206275
TI  - Individualist and collectivist values: hypotheses suggested by Alexis de
      Tocqueville.
AB  - The work of Alexis de Tocqueville, the 19th-century social theorist who coined
      the term individualism, supplied a conceptual foundation for hypothesizing that
      individualism and collectivism, as value systems, should be directly correlated.
      In previous research (D. K.-S. Chan, 1994), individualist and collectivist values
      were negatively correlated in a sample of men, and in a combined sample of men
      and women (P. J. Watson, J. Sherbak, & R. J. Morris, 1998) these values were
      positively correlated. In the present study, a positive relationship was in fact
      observed in both men and women. Linkages with other measures of self and social
      functioning uncovered a few small associations of individualist values with
      maladjustment. Collectivist values predicted adjustment. These data confirm that
      individualist and collectivist values are compatible, just as Tocqueville had
      suggested, and that gender differences do not explain the conflicting results
      previously reported in this literature.

PMID- 12206276
TI  - "Mindless" decision making as a failure of contextual reasoning.
AB  - People often make decisions without reference to vital information, even when
      such information is readily available. In the present research, the authors
      addressed the possibility that this tendency may derive from failure to have
      pertinent information immediately available in the decision context. Participants
      rated the utility of decisions in either the presence or absence of simple
      pertinent information. The information provided required no training and was
      relatively obvious (e.g., if money is spent on a given item, that money will not
      be available for other expenditures). Presentation of such information in the
      immediate context of decisions significantly improved participants' abilities to
      understand their negative consequences. These results indicate that the
      presentation of pertinent information in immediate decision contexts, even
      information that is already available through participants' long-term memory, can
      improve the understanding of decision situations and reduce "mindlessness" in
      decision processes.

PMID- 12206277
TI  - Language and mathematical problem solving among bilinguals.
AB  - Does using a bilingual's 1st or 2nd language have an effect on problem solving in
      semantically rich domains like school mathematics? The author conducted a study
      to determine whether Filipino-English bilingual students' understanding and
      solving of word problems in arithmetic differed when the problems were in the
      students' 1st and 2nd languages. Two groups participated-students whose 1st
      language was Filipino and students whose 1st language was English-and easy and
      difficult arithmetic problems were used. The author used a recall paradigm to
      assess how students understood the word problems and coded the solution accuracy
      to assess problem solving. The results indicated a 1st-language advantage; that
      is, the students were better able to understand and solve problems in their 1st
      language, whether the 1st language was English or Filipino. Moreover, the
      advantage was more marked with the easy problems. The theoretical and practical
      implications of the results are discussed.

PMID- 12206278
TI  - Further psychometric evaluation of the Japanese version of an academic self
      concept scale.
AB  - In the present study, the author replicated earlier research (Paik & Michael,
      1999) seeking additional information on the reliability and construct validity of
      a Japanese academic self-concept scale, a 70-item questionnaire comprising 5
      subscales (Aspiration, Anxiety, Academic Interest and Satisfaction, Leadership
      and Initiative, and Identification vs. Alienation). A sample of 196 Japanese high
      school students completed the scale. Internal consistency reliability for the 5
      subscales ranged from .75 to .87. Confirmatory factor analyses performed on
      several alternative models showed that the a priori 5-factor model fit the
      observed data best-a finding consistent with the previous study. Results of Z
      tests revealed statistically significant score differences between genders and
      between high and low academic achievers.

PMID- 12206279
TI  - Police officer job satisfaction in relation to mood,well-being, and alcohol
      consumption.
AB  - The authors examined job satisfaction, job stress, and thoughts of quitting in
      relation to positive and negative affect, life satisfaction, self-esteem, and
      alcohol consumption among police officers. Exploratory and confirmatory factor
      analyses revealed that 2 dimensions, positive affect and negative affect,
      provided a clear family-tree organizational framework for representing the
      otherwise confusing pattern of associations between job and well-being variables.
      Job satisfaction was primarily associated with positive affect, life
      satisfaction, and self-esteem; job stress was primarily associated with negative
      affect and alcohol consumption; thoughts of quitting had moderate loadings on
      both factors. The 2-dimensional framework may prove useful as a guide in
      reviewing research in this field and in selecting constructs and measures for
      inclusion in future research.

PMID- 12206280
TI  - Phencyclidine (PCP): a dangerous drug, but useful in schizophrenia research.
AB  - Phencyclidine (PCP) is a dangerous drug, and the federal government has placed it
      on Schedule II of the Controlled Substance Act (see http:// www .mninter.net/
      publish/csa2.htm#Schedule%20III). Typically, users smoke PCP, and it is often
      mixed with parsley, marijuana, or cocaine. Most researchers have conducted
      experiments on animals rather than on people, and a few have been done on persons
      diagnosed with schizophrenia, so answers to questions about its addictive
      potential or development of tolerance are not clear. In healthy volunteers, PCP
      can induce symptoms that mimic those of schizophrenia, lasting from a few days to
      more than a week. The neurotransmitter glutamate and N-methyl-D-aspartate (NMDA)
      appear to play a role in the mechanism by which PCP induces positive and negative
      schizophrenic symptoms and cognitive defects (D. C. Javitt & S. R. Zukin, 1991;
      A. Lahti, B. Koffel, D. LaPorte, & C. A. Tamminga, 1995; T. W. Robbins, 1990).
      Because PCP can induce symptoms that are almost indistinguishable from those
      associated with schizophrenia, further research may lead to new medications that
      could be helpful to people who do not respond to neuroleptics that are currently
      available.

PMID- 12206281
TI  - Associations between anxiety and marital adjustment.
AB  - Cognitive-behavioral theories of marital functioning and contextual models of
      close relationships highlight the importance of proximal affect states such as
      anxiety in couple functioning. Despite these assertions, research examining the
      role of state anxiety is lacking in the literature on intimate relationships. In
      this study, the authors examined state anxiety and marital adjustment in a sample
      of 45 couples. Hierarchical regression analyses indicated that husbands' Time 1
      anxiety can predict their own and their wives' subsequent reports of marital
      adjustment. Wives' Time 1 anxiety did not predict their own or their husbands'
      subsequent reports of marital adjustment. In this study, the authors focused on
      the role of husband anxiety in marital adjustment and on implications for further
      study of the contextual model of close relationships.

PMID- 12206282
TI  - A comparison of job performance and disciplinary records of smokers and
      nonsmokers.
AB  - The authors compared job performance and receipt of disciplinary action among
      smoking and nonsmoking hotel employees using organizational records and
      observation. Although smokers and nonsmokers did not differ on 3 measures of
      discipline, there were significant differences on a guest relations performance
      dimension and a summated overall job performance measure. Smokers received higher
      ratings than did nonsmokers. Implications of these findings for the management of
      smoking behavior in the workplace are discussed.

PMID- 12206283
TI  - Time and sensation.

PMID- 12206284
TI  - Barriers to children walking and biking to school--United States, 1999.
AB  - Physical activity is an important part of a healthy lifestyle; however, many
      children in the United States do not meet recommended levels of physical
      activity. Although walking and biking to school can increase physical activity
      among children, motor-vehicle traffic and other factors can make these activities
      difficult. The majority of U.S. children do not walk or bike to school,
      approximately one third ride a school bus, and half are driven in a private
      vehicle. Less than one trip in seven is made by walking or biking. To examine why
      the majority of children do not walk or bike to school, CDC analyzed data from
      the national HealthStyles Survey. This report summarizes the results of that
      analysis, which indicate that long distances and dangerous motor-vehicle traffic
      pose the most common barriers to children walking and biking to school. Public
      health and community-based efforts that encourage walking and biking to school
      should address these barriers.

PMID- 12206285
TI  - School transportation modes--Georgia, 2000.
AB  - Moderate physical activity (e.g., walking or bicycling) offers substantial health
      benefits. Physical activity is especially important for young persons not only
      because of its immediate benefits but also because participation in healthy
      behaviors early in life might lead to healthier lifestyles in adulthood. Persons
      aged > 2 years should engage in > or = 30 minutes of moderately intense physical
      activity on all or most days of the week. However, sedentary after-school
      activities (e.g., watching television or using computers), decreased
      participation in physical education, and fewer students walking or riding their
      bicycles to school might contribute to the high rate of childhood obesity.
      Walking to school provides a convenient opportunity for children to be physically
      active. To examine modes of transportation to school for Georgia children, the
      Georgia Division of Public Health analyzed data from the Georgia Asthma Survey
      conducted during May-August 2000. This report summarizes the results of that
      analysis, which indicate that < 19% of Georgia school-aged children who live < or
      = 1 mile from school walk to school the majority of days of the week. Statewide
      surveillance data of school transportation modes should be collected to monitor
      prevalence of walking to school.

PMID- 12206286
TI  - Serotyping discrepancies in Haemophilus influenzae type b disease--United States,
      1998-1999.
AB  - Since Haemophilus influenzae type b (Hib) conjugate vaccines were introduced in
      the United States in 1990, the incidence of Hib invasive disease has declined
      markedly. The majority of cases of Haemophilus influenzae (Hi) disease are caused
      by organisms with capsule types other than b or by nontypeable organisms. One of
      the national health objectives for 2010 is to reduce to zero indigenous Hib
      invasive disease cases in children aged <5 years (objective 14-1c). In 2000, a
      total of 297 cases of invasive Hi disease were reported in children aged <5
      years; serotype b represented 51 (22%) of 236 cases for which serotype
      information was known. This report describes inconsistencies in Hib serotyping
      between state health departments and CDC; these inconsistencies suggest that the
      burden of Hib disease might be less than estimated previously. Accurate
      laboratory information is essential for the accurate assessment of progress
      toward the elimination of Hib in the United States.

PMID- 12206287
TI  - West Nile virus activity--United States, August 8-14, 2002, and Mississippi, July
      1-August 14, 2002.
AB  - This report summarizes West Nile virus (WNV) surveillance data reported to CDC
      through ArboNET and by states and other jurisdictions as of August 14, 2002.

PMID- 12206288
TI  - Recall of LCx Neisseria gonorrhoeae assay and implications for laboratory testing
      for N. gonorrhoeae and Chlamydia trachomatis.
AB  - On July 18, 2002, Abbott Laboratories (Abbott Park, IL) initiated a voluntary
      recall of its LCx Neisseria gonorrhoeae Assay (List Numbers 8A48-81 and 8A48-82)
      because, during routine quality assurance testing, several reagent lots failed to
      meet the analytical sensitivity described in the product insert. The cause of the
      failure is under investigation by the company. Abbott Laboratories has sent a
      letter to its customers informing them of this recall and the specific reagent
      lot numbers not meeting the analytical sensitivity.

PMID- 12206289
TI  - 2000 SPR Award for distinguished contributions to psychophysiology.

PMID- 12206290
TI  - Aging and the Simon task.
AB  - A visual Simon task was used to study the influence of aging on visuospatial
      attention and inhibitory control processes. Responses were much slower for
      elderly than for young participants. The delay in trials in which stimulus and
      response side did not correspond as compared to when they did correspond (the
      Simon effect) was larger for older people, even after correcting for general
      slowing due to aging. The slowing of responses reflected a slowing of internal
      processing, as indicated by progressively larger delays of the peak latencies of
      the N1, the posterior contralateral negativity (PCN), and P3. A comparison
      between the amplitudes of the PCN and early lateralized readiness potential (pre
      LRP) indicated that transmission from posterior sites (PCN) to the motor cortex
      may be affected by age. The data support the view that aging affects an
      inhibitory process that controls direct visuomotor transmission.

PMID- 12206291
TI  - The effect of background noise on P300 to suprathreshold stimuli.
AB  - Both the amplitude and latency of P300 vary with changes in stimulus parameters.
      Stimuli at intensities or pitch separations near threshold evoke a smaller and
      later P300. P300 is also affected by extraneous stimulus parameters in tasks
      where stimulus frequency separation is large and stimuli are well above intensity
      thresholds. For example, the presence of background white noise when tones are
      suprathreshold and easily detectable has been reported to increase P300 latency.
      However, the effects of background masking noise on P300 amplitude and scalp
      topography have not been reported. Subjects performed an oddball task both in the
      presence and in the absence of background noise. Performance accuracy was
      unaffected by background noise. P300 showed latency increases when noise was
      present, but P300 peak amplitude was unaffected. P300 scalp topography was stable
      across both conditions. P300 latency is affected by background noise, even when
      performance is not, but amplitude and amplitude topography remain unaffected.

PMID- 12206292
TI  - ERD as an index of anticipatory attention? Effects of stimulus degradation.
AB  - Previous research has suggested that the stimulus-preceding negativity (SPN) is
      largely independent of stimulus modality. In contrast, the scalp topography of
      the event-related desynchronization (ERD) related to the anticipation of stimuli
      providing knowledge of results (KR) is modality dependent. These findings,
      combined with functional SPN research, lead to the hypothesis that anticipatory
      ERD reflects anticipatory attention, whereas the SPN mainly depends on the
      affective-motivational properties of the anticipated stimulus. To further
      investigate the prestimulus ERD, and compare this measure with the SPN, 12
      participants performed a time-estimation task, and were informed about the
      quality of their time estimation by an auditory or a visual stimulus providing
      KR. The KR stimuli could be either intact or degraded. Auditory degraded KR
      stimuli were less effective than other KR stimuli in guiding subsequent behavior,
      and were preceded by a larger SPN. There were no effects of degradation on the
      SPN in the visual modality. Preceding auditory KR stimuli no ERD was present,
      whereas preceding visual stimuli an occipital ERD was found. However, contrary to
      expectation, the latter was larger preceding intact than preceding degraded
      stimuli. It is concluded that the data largely agree with an interpretation of
      the pre-KR SPN as a reflection of the anticipation of the affective-motivational
      value of KR stimuli, and of the prestimulus ERD as a perceptual anticipatory
      attention process.

PMID- 12206293
TI  - Changes in the scalp topography of event-related potentials and behavioral
      responses during the sleep onset period.
AB  - Event-related potentials (ERPs) and behavioral responsiveness were investigated
      during the transition from wakefulness to sleep. Ten participants were presented
      with an auditory oddball task during repeated sleep onset periods. The EEG was
      recorded from 29 different scalp sites. A 1500-Hz tone pip was presented
      infrequently (p = .04) within a series of lower pitch 1000-Hz "standard" stimuli
      (p = .96). Participants were required to button press upon detection of the rare
      "target" stimulus. During wakefulness, almost all targets were detected. A large
      amplitude P300 was observed to these detected targets. This P300 was maximum over
      parietal areas of the scalp. During stage 1 sleep, subjects continued to respond
      on 47% of trials. The parietal P300 amplitude remained large to these detected
      targets. It was, however, much attenuated at frontal sites. When the participant
      failed to detect the target in either stage 1 or 2, no P300 was visible. P300 is
      thus associated with behavioral detection of the target stimulus, whether in
      wakefulness or stage 1 "sleep." Trials were also sorted by reaction time (RT), in
      which bins 1-3 represented increasingly long RT. In the waking state, P300
      amplitude did not significantly vary across the different bins. Although mean RT
      latency varied by 512 ms from bin 1 to bin 3, P300 latency varied by only 25 ms.
      Differences in RT are thus probably due to response-related processes rather than
      stimulus classification time.

PMID- 12206294
TI  - Music matters: preattentive musicality of the human brain.
AB  - During listening to a musical piece, unexpected harmonies may evoke brain
      responses that are reflected electrically as an early right anterior negativity
      (ERAN) and a late frontal negativity (N5). In the present study we demonstrate
      that these components of the event-related potential can be evoked
      preattentively, that is, even when a musical stimulus is ignored. Both ERAN and
      N5 differed in amplitude as a function of music-theoretical principles.
      Participants had no special musical expertise; results thus provide evidence for
      an automatic processing of musical information in onmusicians."

PMID- 12206295
TI  - Event-related potentials to auditory stimuli in female Vietnam nurse veterans
      with posttraumatic stress disorder.
AB  - Individuals with posttraumatic stress disorder (PTSD) have been found to show
      several event-related brain potential (ERP) abnormalities including reduced
      target P3b amplitude, P50 suppression, and P2 amplitude/intensity slope. Female
      Vietnam nurse veterans with (n = 29) and without (n = 38) current PTSD completed
      P50 paired-click, three-tone "oddball" and four-tone stimulus-intensity
      modulation procedures. Opposite to previous findings, the current PTSD group had
      larger target P3b amplitudes and increased P2 amplitude/intensity slopes. Reduced
      P50 suppression was associated with increased severity of general
      psychopathology, but not with PTSD diagnosis. Findings suggest that target P3b
      amplitude and P2 amplitude/intensity slope abnormalities reflect different
      pathophysiological processes. Future research is needed to determine whether the
      opposite ERP abnormalities observed in this PTSD sample reflect gender-, trauma-,
      or sample-specific findings.

PMID- 12206296
TI  - A new model of individual differences in hemodynamic profile and blood pressure
      reactivity.
AB  - A quantitative, theory-driven model of hemodynamics was developed, relating
      reactivity in blood pressure to orthogonal dimensions of "hemodynamic profile"
      and "compensation deficit," which were derived from the (multiplicative)
      interaction of cardiac output and total peripheral resistance. A Finapres 2300e
      was used to estimate blood pressure, cardiac output, and total peripheral
      resistance in 100 healthy men and women during mental arithmetic and cold pressor
      tasks on two occasions. Results were consistent with model predictions. As
      predicted, cardiac output and peripheral resistance reactions were curvilinearly
      related, and blood pressure reactivity was strongly related to compensation
      deficit (r = .76-.89). Conversely, the orthogonally defined hemodynamic profile
      remained independent of blood pressure reactivity (r = .11 or less). The data
      show that the present model overcomes several difficulties and inconsistencies in
      previous attempts to obtain an independent measure of hemodynamic profile. The
      new model could help to elucidate sources of cardiovascular pathogenesis not
      suggested from the study of blood pressure reactivity alone.

PMID- 12206297
TI  - The effects of feeding on the electroencephalogram in 3- and 6-month-old infants.
AB  - The human infant's neurophysiological responses to feeding are poorly understood.
      We found recently a significant increase of EEG amplitude in the newborn during
      nutritive feeding, but not during pacifier sucking. In this study, we report EEG
      responses to feeding in 13 infants at the ages of 3 and 6 months. The
      undifferentiated response of the newborn was found to wane until the age of 3
      months, whereas in 6-month-old infants, relatively abundant rhythmic 3-5 Hz theta
      activity was recorded during feeding with an amplitude maximum in right posterior
      areas. Cessation of feeding was followed by cessation of theta activity. The
      rhythmic 3-5 Hz theta response to feeding is likely to represent emotional
      arousal, as it is similar to previous findings showing posterior theta increase
      in other settings connected with emotional arousal in infants.

PMID- 12206298
TI  - Acute psychological stress reduces plasma triglyceride clearance.
AB  - Acute stress elevates blood lipids, with the largest increases among men and
      postmenopausal women. The mechanisms for the effect are unknown, but may be due
      to altered lipid metabolism. This study investigated if acute stress induces
      transient reductions in triglyceride clearance in middle-aged men and women, and
      determined if gender and menopause affect triglyceride metabolism. Of the 35
      women, half were premenopausal, and half were naturally postmenopausal; men (n =
      35) were age matched. Clearance of an intravenously administered fat emulsion was
      assessed twice: once during a nonstress session, and again during a stress
      testing session. During the stress session, a battery of behavioral stressors
      (serial subtraction, speech, mirror tracing, and Stroop) were performed for 40
      min. The clearance rate of exogenous fat was significantly diminished during the
      stress, relative to the nonstress session. Women had more efficient clearance,
      relative to men, but there were no effects of menopausal status. The diminished
      ability to clear an intravenous fat emulsion during stress suggests one mechanism
      for stress-induced elevations in lipids.

PMID- 12206299
TI  - Effects of affective picture viewing and imagery on respiratory resistance in
      nonasthmatic individuals.
AB  - We studied the modulation of oscillatory resistance (R(os)) by viewing and
      imagery of affective pictures. Thirty nonasthmatic participants viewed 36
      affective slides precategorized as positive, neutral, and negative in valence.
      Each picture was presented for 15 s, followed by an imagery epoch of 15 s. R(os),
      facial EMGs, respiration, skin conductance response, heart period, and
      respiratory sinus arrhythmia were measured throughout the session, as well as
      viewing time and ratings of pleasure, arousal, and interest. Increases of R(os)
      were observed for negative pictures, and little changes for positive or neutral
      pictures. Other physiological parameters did not mirror this response pattern,
      leaving no clear indication for a ventilatory or vagal origin of R(os) changes.
      Overall differences between behavioral contexts of visual processing and imagery
      revealed evidence for a coupling of cardiac and respiratory responses, which
      included changes in R(os). The findings in R(os) are discussed in the light of
      earlier discrepant findings on the affective modulation of airway resistance and
      cardiac activity.

PMID- 12206300
TI  - The effect of stimulus probability on P3 in the respiratory-related evoked
      potential.
AB  - The present study investigated the effect of target stimulus probability on the
      P3 component of the respiratory-related evoked potential (RREP). A single
      respiratory stimulus paradigm was employed where normal breaths served as
      standard stimuli and occluded breaths presented at various probability levels
      served as target stimuli. EEG was recorded from 29 channels in young adults in
      two conditions. In Condition 1, occlusions were presented at target probabilities
      of 0.5, 0.33, 0.25, 0.2, 0.1, and 0.05, that is, every 2nd, 3rd, 4th, 5th, 10th,
      and 20th breath. Order of target probability presentation varied randomly.
      Condition 2 used the same target probabilities, but held breathing rate constant
      by using a paced respiration task. Results indicated that P3 amplitude was
      significantly affected by stimulus probability, such that the component showed an
      inverse relationship with probability. This effect was similar between
      conditions. However, P3 amplitude reduced and latency increased when the
      secondary task of paced respiration was introduced. These data suggest that
      models developed to describe the effect of stimulus probability on the amplitude
      of visual and auditory P3 components are applicable to the respiratory
      somatosensory modality.

PMID- 12206301
TI  - Adrenocortical stress responses and altered working memory performance.
AB  - This study examined stress cortisol responses and cognitive performance. We
      initially measured cortisol responses of 40 right-handed healthy male volunteers
      to counterbalanced mental arithmetic and public speaking stressors. We then
      examined the relationship between cortisol reactivity and dichotic listening and
      mental arithmetic performance. High cortisol responders made more errors and
      completed fewer mental arithmetic items than low reactors. On dichotic listening,
      high responders tended toward better performance in all conditions and to both
      ears. High responders showed better performance to the right ear in the forced
      right than in the nonforced condition, whereas no difference between these
      conditions was found in low responders. High cortisol responders may have an
      increased focus on sensory stimuli and a decreased allocation of resources to
      working memory tasks.

PMID- 12206302
TI  - Nucleotide sequences of double-stranded RNA segments from a hypovirulent strain
      of the white root rot fungus Rosellinia necatrix: possibility of the first member
      of the Reoviridae from fungus.
AB  - Twelve double-stranded (ds) RNA segments were detected from a hypovirulent strain
      W370 of the white root rot fungus Rosellinia necatrix. The estimated molecular
      weights ranged from 0.41 x 10(6) to 2.95 x 10(6). Full length cDNA clones for
      eight segments were obtained. Northern blot analysis suggested that each segment
      was genetically unique. The nucleotide sequences of eight full length dsRNA
      segments were determined. One long open reading frame was found in each segment.
      Conserved sequences at the 5'-end (5'-ACAAUUU-3') and at the 3'-end (5'-UGCAGAC
      3') were identified in all eight segments. Segment-specific panhandle structures,
      formed by inverted terminal repeats, were also found in all segments. Comparative
      analyses of the predicted translational products of eight dsRNA segments showed
      that the deduced amino acid sequence partially matched those of the Reoviridae
      family members: Colorado tick fever virus, Nilaparvata lugens reovirus, and rice
      black streaked dwarf virus. The results suggested that W370 dsRNA is derived from
      a new member of the family Reoviridae detected in fungus.

PMID- 12206303
TI  - Drift in the nucleoprotein gene of swine influenza virus (H1N1) causing
      respiratory disease in pigs.
AB  - The nucleoprotein (NP) gene of swine influenza H1N1 variant, A/Sw/Quebec/5393/91
      (SwQc91) was sequenced. When compared with other H1N1 strains, 12 amino acid (aa)
      replacements were observed in the 101-484 aa region of the NP protein including
      two aas, 345 and 430, representing the unique lineage of swine viruses.
      Phylogenetic analysis showed a drift in the NP gene.

PMID- 12206304
TI  - Distinct patterns of mitogen-activated protein kinase phosphorylation and Epstein
      Barr virus gene expression in Burkitt's lymphoma cell lines versus B
      lymphoblastoid cell lines.
AB  - In order to understand mechanistic relationships between signaling pathways
      regulating mitogen-activated protein kinase (MAPK) phosphorylation and Epstein
      Barr virus (EBV) reactivation, we compared MAPK phosphorylation, and EBV
      reactivation and latency in Burkitt's lymphoma cell lines (BLCLs) versus B
      lymphoblastoid cell lines (LCLs). EBV was reactivated in the BLCLs Akata and
      Raji, and in a LCL OB-R33 cells after cross-linking surface immunoglobulin (sIg)
      with anti-Ig. After stimulation with anti-Ig, MAPK phosphorylation was strongly
      induced in all BLCLs and in a few LCLs, but not in other LCLs. MAPK was
      constitutively phosphorylated in most LCLs but not in BLCLs. Expression of EBNA2
      and LMP1, and LMP2A was analyzed with both immunoblotting and RT-PCR. EBNA2 and
      LMP1 were expressed in most LCLs and in some BLCLs. LMP2A was expressed in all
      BLCLs and LCLs except Namalwa cells. To test the hypothesis that LMPI induces
      constitutive MAPK phosphorylation, the LMP1 expression vector was transfected
      into Akata cells. MAPK phosphorylation was not induced in such transfected cells.
      Our results indicate that BLCLs and LCLs respectively have distinct MAPK
      phosphorylation patterns, and that induction of MAPK phosphorylation correlates
      with EBV reactivation in a few cell lines but not in most of the tested cell
      lines.

PMID- 12206305
TI  - Emergence of a new strain of type O foot-and-mouth disease virus: its
      phylogenetic and evolutionary relationship with the PanAsia pandemic strain.
AB  - In India, Foot-and-mouth disease virus (FMDV) serotype O has been associated with
      more than 75% of the outbreaks. Previous studies with this serotype have
      indicated that the viruses circulating in India belong to a single genotype.
      Recent (February 2001) FMD epidemics in Europe have focussed global attention on
      the source of the virus and have been traced to a strain, PanAsia (serotype O),
      which is present in India since 1990. In this study, to further characterize the
      isolates belonging to the PanAsian strain, we sequenced the complete VP1-encoding
      (1 D) gene for 71 FMDV serotype O isolates from India recovered from the field
      outbreaks during the last 4 decades (1962-2001). All the isolates in the tree
      were distributed in to three major branches (designated as A, B and C); the
      branch C is further divided into four groups (I-IV), of which the group IV
      belongs to the PanAsia strain. Furthermore, we show that the PanAsia strain has
      been circulating endemically since 1982 (not 1990 as reported earlier) and has
      been the most dominant outbreak strain in the recent years and distributed at
      least in 17 states of the country. During the year 2001, another new group (group
      III) of virus with genetic divergence of 5.4-11.1% at nucleotide level from the
      PanAsia strain is found to co-circulate endemically, and is slowly replacing it.
      At amino acid level this strain differed from PanAsia strain at five amino acid
      positions in the VP1. Although these strains are divergent at nucleotide level,
      they maintained a good antigenic relationship with one of the vaccine strains
      (IND R2/75) widely used in the country. Given the ability of the PanAsia virus to
      persist, spread and to outcompete other strains, the present trend could be of
      serious concern as the newly emerging virus is replacing it. If this is true,
      then there is another equally divergent strain as PanAsia that may pose a serious
      threat to the global dairy and meat industries.

PMID- 12206306
TI  - The genetic organization of a 2,966 basepair DNA fragment of a single capsid
      nucleopolyhedrovirus isolated from Trichoplusia ni.
AB  - In order to investigate the genomic organization of the Trichoplusia ni Single
      Capsid Nucleopolyhedrovirus (TnSNPV), a 2,966 basepairs (bp) genomic fragment was
      sequenced. The fragment was found to contain five open reading frames (ORFs)
      homologous to baculovirus genes, including p26, fibrillin (p10), AcMNPV ORF-29,
      late expression factor 6 (lef-6) and the C-terminal portion of p74, on either
      strand of DNA. Predicted amino acid sequences for the ORFs were compared and
      identity values of between 12% and 54% were observed. TnSNPV has previously been
      tentatively identified as a member of the Group II NPVs. Clustering and
      arrangement of the TnSNPV genes were similar to the clustering reported for
      SeMNPV, confirming TnSNPV as a Group II NPV.

PMID- 12206308
TI  - High-level expression of the C-terminal hydrophobic region of HCV E2 protein
      ectodomain in E. coli.
AB  - High-level expression of hepatitis C virus (HCV) E2 protein fragments
      encompassing its C-terminal hydrophobic region (downstream of aa 661) in
      Escherichia coli has been proven difficult. The extreme hydrophobicity of this
      region has been suspected to be detrimental to the host. In this work, we found
      that the C-terminal region (downstream of aa 565) of E2 ectodomain interfered
      with full-length expression of E2 fragments in E. coli. Nonetheless, when the
      central region (aa 484-622) of E2 was deleted, full-length protein was
      efficiently produced. C-terminal region aa 567-700 could not be efficiently
      expressed individually or as mouse dihydrofolate reductase (DHFR) fusion protein.
      However, a mutant that emerged in the cloning process was able to express full
      length DHFR fusion protein. Sequencing analysis reveals the mutation to be a
      short frame-shift around the fusion junction, altering aa 568-571 of E2. C
      terminal region of E2 ectodomain (aa 567-730) carrying this mutation was
      successfully expressed as hexa-histidine-tagged protein to a high level. The
      protein was highly insoluble and was purified under denaturing conditions. The
      purified protein displayed HCV E2-specific antigenicity in Western blot and
      specific rabbit antiserum was raised against it. These results demonstrate that
      hydrophobicity of the C-terminal region of E2 ectodomain is not harmful to E.
      coli host and has no dominative adverse effect on its bacterial expression. Other
      nucleotide and/or amino acid sequence properties seem to play a more important
      role. This finding opens up new possibilities for the development of novel
      bacterially-derived E2 proteins for research and clinical applications.

PMID- 12206307
TI  - Transgenic plants expressing HC-Pro show enhanced virus sensitivity while
      silencing of the transgene results in resistance.
AB  - Nicotiana benthamiana plants were engineered to express sequences of the helper
      component-proteinase (HC-Pro) of Cowpea aphid-borne mosaic potyvirus (CABMV). The
      sensitivity of the transgenic plants to infection with parental and heterologous
      viruses was studied. The lines expressing HC-Pro showed enhanced symptoms after
      infection with the parental CABMV isolate and also after infection with a
      heterologous potyvirus, Potato virus Y (PVY) and a comovirus, Cowpea mosaic virus
      (CPMV). On the other hand, transgenic lines expressing nontranslatable HC-Pro or
      translatable HC-Pro with a deletion of the central domain showed wild type
      symptoms after infection with the parental CABMV isolate and heterologous
      viruses. These results showed that CABMV HC-Pro is a pathogenicity determinant
      that conditions enhanced sensitivity to virus infection in plants, and that the
      central domain of the protein is essential for this. The severe symptoms in CABMV
      infected HC-Pro expressing lines were remarkably followed by brief recovery and
      subsequent re-establishment of infection, possibly indicating counteracting
      effects of HC-Pro expression and a host defense response. One of the HC-Pro
      expressing lines (h48) was found to contain low levels of transgenic HC-Pro RNA
      and to be resistant to CABMV and to recombinant CPMV expressing HC-Pro. This
      indicated that h48 was (partially) posttranscriptionally silenced for the HC-Pro
      transgene inspite of the established role of HC-Pro as a suppressor of
      posttranscriptional gene silencing. Line h48 was not resistant to PVY, but
      instead showed enhanced symptoms compared to nontransgenic plants. This may be
      due to relief of silencing of the HC-Pro transgene by HC-Pro expressed by PVY.

PMID- 12206309
TI  - Genetic organization and sequence analysis of pVIII, fiber and early region 4 of
      bovine adenovirus type 7.
AB  - The DNA sequence of 8,810 nucleotides at the right end of bovine adenovirus type
      7 (BAV7) genome was determined and compared with similar regions of other
      adenoviruses. This genomic region of BAV7 consists of sequences encoding partial
      33K, pVIII, fiber, putative early region 4 (E4) proteins and other unassigned
      proteins. However, BAV7 E3 region is not present in the expected location between
      pVIII and fiber as BAV7 intergenic region between pVIII and fiber genes is only
      183 nucleotides. The predicted pVIII and fiber demonstrates highest homology to
      corresponding proteins of ovine adenovirus 287 (OAV287), bovine adenovirus-4
      (BAV4) and egg drop syndrome virus (EDSV). The E4 region encodes three ORFs,
      which shows significant homology only to corresponding proteins encoded by E4
      region of OAV287 and BAV4. Sequence comparisons, phylogenetic analysis and
      overall genome organization in this region of BAV7 provide further evidence for
      the inclusion of BAV7 together with OAV287, BAV4, and EDSV in the proposed genus
      'Atadenovirus'.

PMID- 12206310
TI  - Complete nucleotide sequence, genome organization and phylogenic analysis of the
      canine calicivirus.
AB  - The complete genomic sequence of canine calicivirus (CaCV) isolated from feces of
      a dog with diarrhea was determined. The CaCV genome, a positive-sense single
      stranded RNA, contained 8513 nucleotides excluding the poly(A) tail and was
      longer than that of any other calicivirus strain with a completely known
      sequence. There were three open reading frames (ORF1, nt 12-5801; ORF2, nt 5805
      7880; and ORF3, nt 7877-8278). ORF1 encoded a polyprotein (calculated Mr of
      214,802) which had the conserved motifs of non-structural proteins of other
      caliciviruses and picornaviruses. Regions containing characteristic motifs in the
      non-structural polyprotein of CaCV showed highest similarity with those of the
      species Feline calicivirus and Vesicular exanthema of swine virus in the genus
      Vesivirus. Phylogenic analysis indicated that CaCV formed a distinct branch
      within the genus. Our results strongly suggested that CaCV is a new species in
      the genus Vesivirus.

PMID- 12206311
TI  - The molecular variability analysis of the RNA 3 of fifteen isolates of Prunus
      necrotic ringspot virus sheds light on the minimal requirements for the synthesis
      of its subgenomic RNA.
AB  - The nucleotide sequences of the RNA 3 of fifteen isolates of Prunus necrotic
      ringspot virus (PNRSV) varying in the symptomatology they cause in six different
      Prunus spp. were determined. Analysis of the molecular variability has allowed,
      in addition to study the phylogenetic relationships among them, to evaluate the
      minimal requirements for the synthesis of the subgenomic RNA in Ilarvirus genus
      and their comparison to other members of the Bromoviridae family. Computer
      assisted comparisons led recently to Jaspars (Virus Genes 17, 233-242, 1998) to
      propose that a hairpin structure in viral minus strand RNA is required for
      subgenomic promoter activity of viruses from at least two, and possibly all five,
      genera in the family of Bromoviridae. For PNRSV and Apple mosaic virus two stable
      hairpins were proposed whereas for the rest of Ilarviruses and the other four
      genera of the Bromoviridae family only one stable hairpin was predicted.
      Comparative analysis of this region among the fifteen PNRSV isolates
      characterized in this study revealed that two of them showed a 12-nt deletion
      that led to the disappearance of the most proximal hairpin to the initiation
      site. Interestingly, the only hairpin found in these two isolates is very similar
      in primary and secondary structure to the one previously shown in Brome mosaic
      virus to be required for the synthesis of the subgenomic RNA. In this hairpin,
      the molecular diversity was concentrated mostly at the loop whereas compensatory
      mutations were observed at the base of the stem strongly suggesting its
      functional relevance. The evolutionary implications of these observations are
      discussed.

PMID- 12206312
TI  - Molecular characterization of three new avian infectious bronchitis virus (IBV)
      strains isolated in Quebec.
AB  - Three unrecognized field isolates of Infectious Bronchitis Virus (IBV) were
      recovered from commercial broiler chickens vaccinated with live Mass viral strain
      (H120). These isolates were identified by immunofluorescence using monoclonal
      antibodies produced against reference serotypes: Mass, Conn, and Ark. RT-PCRs
      were performed on viral RNAs to amplify S1 gene using a specific set of primers
      S1OLIGO3' and S1OLIGO5'. Restriction polymorphism (RFLP) of PCR products was
      determined by the use of HaeIII restriction enzyme. As expected, patterns of PCR
      products were different from common pattern of strains assigned to Mass serotype
      M41, Beaudette, H120, and Florida. Molecular analysis showed a nucleotide
      insertion in hypervariable region one (HVR-1) of S1 gene of only Quebec isolates
      (Qu16, Qu_mv and Q_37zm). However, New Brunswick IBV isolate (NB_cp) did not
      display these insertions. Major amino acid changes involved insertion of two
      stretches (aa118-119: Arg-Ser and aa141-145: Sys-Ser-Asn-Ala-Ser-Cys) located at
      N-terrminal and C-terminal regions of HVR-2. It is speculated that cysteine
      residue located upstream and downstream of Cys-Ser-Asn-Ala-Ser-Cys segment might
      be involved in the formation of loop structure and disulfide bond that could
      trigger important epitope changes. Insertion of new NXT and NXS (X not equal to
      P) glycosylation motifs scattered along S1 region and insertion of cysteine
      residues in HVR are contributing to the antigenic shifting of Quebec isolates.
      Fragment insertions were thought to be induced by inter-serotype recombination
      between vaccine strain (H120) that belongs to Mass serotype and another strain
      belonging to Ark serotype. Phylogenetic tree based on amino acid sequences showed
      that Quebec isolates formed a new phylogenetic cluster.

PMID- 12206314
TI  - Comments to the paper of H.S. Randhawa, A.Y. Mussa & Z.U. Khan: Decaying wood in
      tree trunk hollows as a natural substrate for Cryptococcus neoformans and other
      yeast-like fungi of clinical interest--Mycopathologia 151: 63-69, published in
      July 2001.

PMID- 12206313
TI  - Sequence analysis of the S3 gene from a turkey reovirus.
AB  - The deduced sigma-2 protein sequence from the S3 gene segment of a novel turkey
      reovirus, designated NC98, isolated from the bursa of birds exhibiting poult
      enteritis and mortality syndrome was determined. The isolate, serologically
      distinct from other avian reoviruses, was isolated in turkey embryo kidney cells
      and RNA was purified for cDNA synthesis. Oligonucleotide primers were designed
      based on conserved avian S3 nucleotide sequence data. The NC98 S3 open reading
      frame comprised 1,101 base pairs and encoded 366 amino acids with a predicated
      molecular mass of 40.5 kDa. Although the S3 nucleotide sequence from several
      chicken isolates share at least 86% identity, they share only 64% with the NC98
      turkey isolate. Interestingly, the S3 nucleotide sequence from a muscovy duck
      reovirus shares 55% identity with NC98 and 53% identity with chicken isolates. As
      observed in other avian reovirus sigma2 protein sequences, a zinc-binding motif
      and double-stranded RNA binding domain were found within the predicted amino acid
      sequence of NC98. Phylogenetic analysis of the deduced sigma2 sequence
      demonstrated that NC98 separated as a distinct virus relative to other avian
      strains. The results of this study indicate that NC98 is a novel turkey reovirus
      that shares limited genomic sequence identity to isolates of chicken and duck
      origin and should be considered a separate virus species within subgroup 2 of the
      Orthoreovirus genus.

PMID- 12206315
TI  - Deep dermatophytoses in association with atopy and diabetes mellitus: Majocchi's
      granuloma tricophyticum or dermatophytic pseudomycetoma?
AB  - Two patients presenting with subcutaneous nodules, plaques, papules and
      ulceration caused by dermatophytes are described in this report. The first case
      was atopic and had used low dose systemic corticosteroids intermittently for his
      asthma. The second case was a poorly controlled and long-standing diabetic
      patient. The diagnoses were suspected after direct microscopical examinations of
      the discharge materials which revealed the presence of hyaline hyphae and spores,
      and histological examination which showed an inflammatory infiltrate with fungal
      elements in the dermis. Cultures of puncture materials and skin biopsies
      confirmed the diagnosis identifying Trichophyton rubrum and T. mentagrophytes var
      interdigitale, in the first and second case respectively. Antifungal therapy with
      itraconazole was successful in both patients. The cases are presented to
      emphasize the possibility of this unusual condition in association with atopy and
      diabetes mellitus as in profoundly immunosuppressed cases. The nomenclature
      concerning this type of dermatophyte infections is also discussed.

PMID- 12206316
TI  - Incidence of dermatophytes and cyclohexamide resistant fungi on healthy children
      hairs and nails in nurseries.
AB  - In order to estimate the prevalence of dermatophytes and other fungi on healthy
      children hairs and nails, 92 hair samples and 85 nail samples (groups of 10
      finger nails from each child) were collected from 5 nurseries (children aged 9
      months up to 4 years) in Assiut city. From hair samples 22 species were
      collected, Trichophyton (2 species) and Microsporum (2 species) were the only
      recovered dermatophytes in addition to well known keratinophilic genus
      Chrysosporium (4 species). From nail samples, 18 species were identified,
      Trichophyton was represented by 4 species, Microsporum, 2 species and
      Chrysosporium, 4 species. Also, several other saprophytes and cycloheximide
      resistant fungi were isolated.

PMID- 12206317
TI  - Studies on the fungal infestation of five traditionally smoke-dried freshwater
      fish in Ago-Iwoye, Nigeria.
AB  - Samples of traditionally smoke-dried Clarias gariepinus (Burchell), Chrysichthys
      nigrodigitatus (Lacepede), Sarotherodon galilaeus (Trewavas), Heterotis niloticus
      (Cuvier) and Heterobranchus bidorsalis (Geoffroy) were obtained from Oja Oba
      Market, Ago-Iwoye, Nigeria and examined for fungal infestation. The fish samples
      incubated on potato dextrose agar (PDA) for 7 days showed fungal infestation.
      Fungi isolated and identified included Mucor sp., Aspergillus sp., Rhizopus sp.
      and Fusarium sp. Six fungal species were isolated from C. nigrodigitatus, five
      each on C. gariepinus and H. niloticus.

PMID- 12206318
TI  - Candida parapsilosis peritonitis in patients on CAPD.
AB  - Twenty-four episodes of C. parapsilosis peritonitis in 23 patients on continuous
      ambulatory peritoneal dialysis (CAPD) over 6 years were reviewed. Clinical
      manifestations and laboratory findings were similar to those of other pathogens.
      All started treatment with intravenous amphotericin B. In six cases it was
      attempted to maintain a peritoneal catheter in situ, but removal became essential
      to relieve fungal peritonitis. Of the patients who developed peritonitis, 15
      episodes (62.5%) continued the CAPD program. Nine cases could not resume CAPD
      because of death in 4, patient preference in 2, and abdominal adhesion in 3.
      Antifungal treatment alone was ineffective in most cases. It was found that
      peritonitis developing after gram negative bacterial peritonitis and the use of
      fluconazole after catheter removal were associated with CAPD discontinuation. It
      was suggested that C. parapsilosis peritonitis in CAPD patients should be treated
      with rapid catheter removal, particularly those with fungal peritonitis who had
      prior gram negative peritonitis.

PMID- 12206319
TI  - Degradation of keratin substrates by fungi isolated from sewage sludge.
AB  - Four fungal species including two dermatophytes and two saprophytes were isolated
      from sewage sludge samples at Basrah (Iraq) they were tested for their
      degradative ability towards three types of keratin substrates (human hair,
      chicken feathers and wool). The rate of keratin degradation was expressed as
      weight loss over three weeks of incubation using a liquid culture medium. Human
      hair had the highest degradation rate by colonization of Chrysosporium pannicola
      and Microsporum gypseum at a rate of 62% and 48% respectively. Chicken feathers
      were highly degraded by Aspergillus flavus (32%) while wool degradation was
      highest by C. pannicola (45.5%) and Trichophyton mentagrophytes var. erinacei
      (38%). There was a significant difference (p < 0.001) in keratin substrate
      degradation rates by the examined fungi. Keratinase activity was highest for C.
      pannicola and M. gypseum in the culture medium baited with human hair.
      Aspergillus flavus revealed the highest activity of this enzyme in cultures
      amended with chicken feathers while T mentagrophytes var. erinacei showed highest
      keratinase activity in cultures with wool substrate. The amount of protein
      released into the culture medium varied among the tested fungi. The medium's
      alkalinity increased over incubation time from 6.5 to 7.8. Microscopic
      examination showed maceration of the keratin substrates by the fungi.

PMID- 12206320
TI  - In vitro, greenhouse and field assessments of cassava lines for resistance to
      anthracnose disease caused by Colletotrichum gloeosporioides f.sp. manihotis.
AB  - Fifty-three cassava lines were selected from breeding populations at the
      International Institute of Tropical Agriculture (IITA), Ibadan, Nigeria and
      screened in vitro for resistance to cassava anthracnose disease (CAD). The in
      vitro inoculation of stem cuttings with the fungus Colletotrichum gloeosporioides
      f.sp. manihotis showed significant differences (p +/- 0.05) in acervuli
      production and in the sensitivity of the cassava lines to the fungal infection
      after 7 days of incubation at 25 degrees C. Cassava lines 88/01084, 91/00595,
      91/00475, 91/00344, 91/00684, 91/00313, 91/00422, and 91/00344 were highly
      resistant, with necrotic lesion sizes less than 7 mm. In contrast pedigree lines
      88/02549, 89/0008, 91/00390 and 91/00402 were highly susceptible with the largest
      necrotic lesion size being greater than 20 mm. Ten cassava lines from the in
      vitro screening that showed varying levels of resistance to CAD were selected,
      based on their flowering abilities for diallel hydridization trials, and were
      further screened in greenhouse and field trials for CAD resistance. The
      greenhouse and field screening showed significant varietal differences (p +/-
      0.05) in sensitivity to the fungus. In all cases, the progeny lines showed
      correlated levels of resistance irrespective of the type of screening or
      assessments. Correlation analysis of the in vitro, greenhouse and field
      assessments showed that there was a good correspondence among all three methods
      of evaluating for CAD.

PMID- 12206321
TI  - Agalactia in mares fed with grain contaminated with Claviceps purpurea.
AB  - This article reports an outbreak of intoxication of female horses with Claviceps
      purpurea in southern Brazil. The outbreak affected twelve pregnant mares which
      were fed with black oat (Avena strigosa) during the pre-delivery period.
      Underdevelopment of the mammary gland in the pre-delivery period resulting in
      post-delivery agalactia was the most pronounced finding. These mares delivered
      weak and unviable foals, which showed no suckling reflex and died within a few
      hours of birth. Laboratory analysis of oat samples fed to the animals resulted in
      the identification of Claviceps purpurea sclerotia. The fungus was identified in
      0.22% of the examined seeds.

PMID- 12206322
TI  - Metabolite profiles of Stachybotrys isolates from water-damaged buildings and
      their induction of inflammatory mediators and cytotoxicity in macrophages.
AB  - The metabolite profiles of 20 Stachybotrys spp. isolates from Finnish water
      damaged buildings were compared with their biological activities. Effects of
      purified compounds on cytotoxicity and production of inflammatory mediators such
      as nitric oxide, IL-6 and TNFalpha in murine RAW264.7 macrophage cells were
      studied. The 11 isolates belonging to the satratoxin-producing chemotype were
      highly cytotoxic to the macrophages. The isolates inducing inflammatory mediators
      all belonged to the atranone-producing chemotype, but pure atranones B, and D did
      not elicit a response in the bioassay. Altogether, cytotoxicity of Stachybotrys
      sp. isolates appear to be related to satratoxin production whereas the specific
      component inducing inflammatory responses in atranone-producing isolates remains
      obscure.

PMID- 12206323
TI  - Isolation of Beauveria bassiana and Metarhizium anisopliae var. anisopliae from
      Boophilus microplus tick (Canestrini, 1887), in Rio de Janeiro State, Brazil.
AB  - The objective of this work were to isolate and identify strains of
      entomopathogenic fungi from ingurgitated female Boophilus microplus ticks,
      collected from the soil in the municipality of Paracambi, Rio de Janeiro State,
      Brazil. The ingurgitated females were inoculated in the selective medium oat
      dodine agar (oda), where 49 colonies of Beauveria bassiana (71%) and 20 of
      Metarhizium anisopliae var. anisopliae (29%) were isolated. These isolated
      strains characterize for the first time in Brazil the natural occurrence of these
      species of fungi in this tick, and will be used to conduct bioassays to evaluate
      the pathogenicity and virulence of these strains for ticks of the genus Boophilus
      microplus.

PMID- 12206324
TI  - A new practice analysis of hand therapy.
AB  - The Hand Therapy Certification Commission, Inc. (HTCC) conducted a role
      delineation in 2001 to characterize current practice in the profession of hand
      therapy. Building upon previous HTCC studies of practice (i.e., Chai, Dimick &
      Kasch, 1987; Roth, Dimick, Kasch, Fullenwider & Taylor, 1996), subject matter
      experts identified the clinical behaviors, knowledge, and technical skills needed
      by hand therapists. A large scale survey was conducted with therapists across the
      United States and Canada who rated the clinical behaviors, knowledge, and
      technical skills in terms of their relevance to practice, and provided
      information about their own patient populations. A high survey return rate (72%)
      was indicative of the professional commitment of CHTs to their profession.
      Results of the survey are discussed and practice trends are identified. A new
      test outline for the Hand Therapy Certification Examination was created based on
      the results of the survey, and the 1987 Definition and Scope of Hand Therapy was
      revised.

PMID- 12206325
TI  - Comparison of range-of-motion constraints provided by prefabricated splints used
      in the treatment of carpal tunnel syndrome: a pilot study.
AB  - Nocturnal splinting of the wrist is commonly used to treat carpal tunnel
      syndrome. Rationales for overnight wrist splinting are based on several research
      studies, which suggest that passively and actively sustained positions of the
      wrist and digits during sleep contribute to elevated carpal tunnel pressures. The
      types of splints used for carpal tunnel syndrome include custom and prefabricated
      orthoses of many variations. The purpose of this paper is to assess the resting
      and passive range-of-motion position restrictions and parameters provided by four
      prefabricated orthoses commonly prescribed for or used by patients at the
      authors' treatment facility. A literature review provides information that
      supports optimal wrist and finger positioning to minimize resting carpal tunnel
      pressures. This information may be useful in determining the most effective
      splint design choices.

PMID- 12206326
TI  - The prevalence of occupational injuries among hand therapists in Australia and
      New Zealand.
AB  - Little research has been dedicated to the prevalence of occupational injury among
      hand therapists (occupational therapists and physiotherapists). This study
      investigates the prevalence of occupational injuries and pain in hand therapists
      in Australia and New Zealand. Another aim of the study was to identify risk
      factors and prevention strategies. A questionnaire was distributed to 155
      therapists in Australia and New Zealand. One hundred and ten questionnaires were
      returned and analyzed. Results indicated a significant prevalence of primarily
      hand and upper limb injuries in hand therapists. There were 148 injuries
      discussed by 73 participants. Of these, 75% were described as work-related
      injuries. Forty percent of participants described two or more current injuries or
      pain sites. The most commonly reported occupational injury or pain was around the
      metacarpophalangeal or carpometacarpal thumb joint. Analysis of data showed no
      characteristics of participants that particularly put them at risk. There was no
      statistically significant difference in the incidence of injury in relation to
      hours of work, handedness, time since graduation, age, or sex. Participants
      identified possible causes of occupational injury and pain and prevention
      strategies. Further studies need to assess correlation between anthropometric
      measures and the prevalence of occupational injury. Studies also need to
      investigate specific prevention strategies.

PMID- 12206327
TI  - Simultaneous bilateral testing: validation of a new protocol to detect insincere
      effort during grip and pinch strength testing.
AB  - The detection of feigned weakness in hand grip strength assessment is difficult.
      The authors review several proposed methods and their weaknesses. A comparison of
      unilateral testing and simultaneous bilateral testing with the Jamar dynamometer
      and the Baseline pinch gauge is demonstrated as a solution. An experiment
      involved 100 asymptomatic subjects who were tested twice, once under instructions
      to give a full effort and once under instructions to feign weakness. Seven
      statistical criteria of noncompliance were chosen. Defining noncompliance as
      failing two or more of the seven criteria, 99% of the instructed noncompliant
      subjects were correctly classified as noncompliant. No subjects were incorrectly
      classified as noncompliant during instructed compliant testing. Twelve subjects
      failed on a single criterion. On retesting, all but one were correctly
      classified. One subject in the instructed noncompliant group passed all criteria.
      Accuracy was 99.5%, including retesting of the 12 "gray-zone" subjects.

PMID- 12206328
TI  - Treatment of worker's compensation cases of carpal tunnel syndrome: an outcome
      study.
AB  - The primary goal of this retrospective study was to determine the most effective
      treatment protocol to return worker's compensation patients with carpal tunnel
      syndrome (CTS) to their original jobs. By examining a homogeneous subject pool
      and using specific, functional outcome measures determined by what is needed to
      reduce worker's compensation costs, a treatment protocol could be developed
      benefiting both the employer and employee. A total of 121 charts of worker's
      compensation patients with diagnoses of work-related CTS were reviewed. For
      inclusion in the study, patients could have no other upper extremity disorder,
      they must have completed treatment for the CTS, and the etiology of their CTS
      could not be traumatic. A total of 58 patients were included. Those who received
      conservative treatment followed by surgery (n = 27) were compared with those who
      were treated with surgery only (n = 31). A chi-square test showed a significant
      relationship between type of treatment and return to work (chi2(1)=4.065;
      p=0.044). Of the 31 patients who received only surgical treatment, 83.9% returned
      to original employment. Of the 27 patients who received both conservative and
      surgical treatment, 59.1% returned to their original employment. While this is a
      small sample size, the findings suggest that conservative treatment alone is not
      effective in returning worker's compensation patients with CTS to work.

PMID- 12206329
TI  - Krukenberg kineplasty: a case study.
AB  - Functional independence has always been one of the most important goals in hand
      therapy. Following below-elbow amputation, this goal is often achieved by means
      of a prosthetic device. Unfortunately, there are rare instances in which an
      individual possesses an additional debilitating injury, such as blindness, that
      may preclude the use of a prosthetic device. Few hand therapists or surgeons
      actually have the opportunity to treat this type of patient. The purpose of this
      case study is to report the surgical methods, assessment techniques, and therapy
      guidelines for a 13-year-old male patient who suffered a below-elbow amputation
      of the left upper extremity and loss of vision after stepping on a land mine in
      his native country, Nicaragua.

PMID- 12206330
TI  - Management of a proximal interphalangeal joint fracture dislocation with a
      compass proximal interphalangeal joint hinge and therapy: a case report.
AB  - The purpose of this report is to describe the management of a chronic proximal
      interphalangeal (PIP) joint fracture dislocation in a 46-year-old computer
      programmer. Twenty days following injury, a right ring finger volar plate
      arthroplasty was performed, loose fracture fragments were excised, and a Compass
      PIP joint hinge was applied. The hinge was locked at 10 degrees to 15 degrees
      extension and held in this position for 8 days. On postoperative day 8, hand
      therapy was initiated. Many challenges were encountered. Insurance constraints
      required the patient to change therapists. The device frame cracked. The patient
      developed a PIP joint contracture with extensor lag. Despite these obstacles, the
      patient achieved a successful outcome, returning to normal pain-free use with
      grip strength at 87% of that of the uninvolved hand. At discharge, active range
      of motion was 12 degrees/100 degrees at the PIP joint and 0 degrees/40 degrees at
      the DIP joint. Passive extension was 0 degrees. At 6 months postoperatively,
      active range of motion was 0 degrees/105 degrees at the PIP joint and 0
      degrees/60 degrees at the DIP joint. This case demonstrates the need for closely
      supervised postoperative therapy that includes good communication between
      providers, ongoing patient education, and close monitoring of range of motion.

PMID- 12206331
TI  - Function of the upper extremity and ability to perform housework following
      reconstructive surgery of the shoulder joint using a free vascularized fibula
      bone graft: a case report.
AB  - The cases of two female patients who underwent reconstructive surgery using free
      vascularized fibular bone grafting of the proximal humerus are reported. Both
      patients were evaluated 1 year postoperatively for active range of motion; an
      Enneking evaluation and activities-of-daily-living (housework) assessment were
      also done. Patient 1 regained flexion and abduction to 110 degrees, and patient 2
      regained flexion and abduction to 90 degrees. On the Enneking test, the patients
      achieved scores of 23 and 25 points, respectively. On the activities-of-daily
      living housework assessment, patient 1 performed at 91.0% and patient 2 at 60.6%.
      In both cases, neither active range of motion nor the Enneking scores accurately
      reflected the functional abilities of the reconstructed limbs. It is important
      that upper extremity therapists evaluate and consider functional abilities in
      activities of daily living, such as housework, in the early phases of
      rehabilitation.

PMID- 12206332
TI  - Splint for the re-education of the transferred tendon-muscle unit.

PMID- 12206334
TI  - Biological warfare.

PMID- 12206333
TI  - Keeper of the flame.

PMID- 12206335
TI  - Self-extubation in intensive care and re-intubation predictors: a retrospective
      study.
AB  - To find out the incidence of self-extubation in intensive care, to evaluate the
      factors responsible for it and to identify the predictors of need for re
      intubation, a retrospective analysis was conducted among 350 patients who were
      admitted to the intensive care unit over a two-year period and required
      ventilatory therapy for more than 48 hours. In all patients who self-extubated,
      the demographic data, ventilatory parameters before self-extubation (mode of
      ventilation, inspired oxygen concentration, positive end-expiratory pressure),
      partial pressure of oxygen in arterial blood and inspired oxygen fraction ration
      (PaO2/FiO2), and the event of re-intubation were noted. These values were
      compared among patients who were re-intubated and those who were not. Twelve
      patients out of 350 self-extubated. Of these 12 patients, 7 required re
      intubation while 5 did not. Of these 7 patients, 3 died within 48 hours of the
      episode of self-extubation and one patient's death was directly attributable to
      self-extubation. Of the remaining 4 patients, 3 died within a span of 7 days. Re
      intubation after self-extubation should not be considered mandatory. Patients who
      required re-intubation had lower PaO2/FiO2 than patients who did not.

PMID- 12206336
TI  - Role of potassium hydroxide mount in rapid diagnosis of fungal corneal ulcers.
AB  - The aim of the study was to establish the importance of KOH mount in rapid
      diagnosis of fungal corneal ulcers. Corneal scrapings were collected from 50
      patients with corneal ulcers where clinical features suggested fungal aetiology
      and ulcers showed no signs of healing on initial treatment. Corneal scrapings
      were subjected to wet mount with 10% KOH, Gram's stain, and culture on SDA media.
      Wet mount showed fungal elements in 34 cases (68%) and were classified according
      to morphology. Gram's stain of corneal scrapings did not provide much help.
      Fungal culture was positive in 9 (26.4%) out of 34 cases. Specific antifungal
      treatment was instituted in all cases that showed positive wet mount without
      waiting for culture reports and on follow-up all these 34 patients showed
      improvement. Thus wet mount with 10% KOH can be relied upon as the singlemost
      important screening tool for rapid diagnosis of fungal corneal ulcer and
      treatment should be dispensed on its basis.

PMID- 12206337
TI  - Pulmonary hydatidosis--a surgical experience.
AB  - Twenty-five cases of pulmonary hydatid cysts were studied with emphasis on age,
      sex and site distribution. In the present study, the youngest patient was of 4
      years. Male predominance (2.125:1) with peak incidnce at 21-40 years was
      observed. Right lung was involved more frequently. Pain chest and haemoptysis
      were the commonest symptoms. No recurrence and no mortality were reported.

PMID- 12206338
TI  - Optimal age for measles vaccination.
AB  - Children in the age groups of 6-9 (group I) and >9-12 months (group II, control)
      75 in each group, sex-matched were studied for antimeasles antibodies IgG and IgM
      by ELISA technique, before immunisation with Schwarz strain of measles vaccine.
      IgG antibodies were found in 66% in group I and none in group II, indicating the
      waning of maternal antibodies at an early age which come down before 6 months of
      age. After administration of measles vaccine to both the groups seroconversion
      was estimated at intervals of 4 weeks and 6 months after vaccination. Antimeasles
      IgM antibodies increased after vaccination and decreased 6 months after
      vaccination in both groups. Antimeasles IgG antibodies showed a significant
      increase in both groups. Increase was high in group II. This shows that anti-IgG
      antibodies to measles increased with age. The study shows the disappearance of
      protective level of immunisation at an early age. Seroconversion following
      vaccination at the age of 6 months is low, and hence a booster dose is
      recommended at 15 months.

PMID- 12206339
TI  - Management of low back pain.
AB  - A sizeable section of world's population develop back pain sometime in their
      lives and the specific causes cannot be identified. Various clinical conditions
      like trauma, infection (tuberculous, pyogenic, etc), malignancy, rheumatological
      diseases, neurological disorders and degenerative diseases produce back pain, and
      also some systemic illnesses cause the same. Radiological studies are very
      important for the diagnosis of back pain. Plain radiographs, myelography,
      computed tomography, magnetic resonance imaging and bone scintigraphy are various
      radiological procedures often selected for diagnosis. Treatment modality
      comprises non-surgical and surgical methods. Non-surgical treatment consists of
      rest, pharmacological therapy, physical therapy and injection therapy. Disc
      surgery, widening of spinal canal, spinal fusion using bone grafts, removal of
      tumour or sequestrated disc are carried out when surgical intervention is needed.

PMID- 12206340
TI  - Fatal promise of immortality.
AB  - The Census of 2001 brings the heartening news that the secular decline in the sex
      ratio of file population has come to a halt: The sex ratio in the population has
      increased from 927 females per thousand males to 933 females per thousand males
      in 2001. However it also brings disturbing figures of the continuing decline in
      the sex ratio in the 0-6 years age group. Partly due to higher female mortality
      in this age group, demographers had agreed that it is also due to female
      foeticide, the sex-selective abortion of female foetuses. The figure for the
      number of females per 1000 males has come down from 945 in 1991 to 927 in 2001.
      Some states in the country, Himachal Pradesh, with a decline of 54, Punjab of 82,
      Haryana of 59, and Delhi and Gujarat of 50 each, have shown more precipitous
      declines. Indeed the sex ratio at birth, based on the SRS, points to an
      increasing masculinisation from 109.5 males per 100 females in 1990 to 111.0
      males per 100 females in 1998. As a consequence there has been a great deal of
      official concern, the Indian Medical Association initiated a campaign to
      sensitise the public, the Supreme Court has instructed states to implement the
      Prenatal Diagnostic Techniques (PNDA) Act, and so-called religious leaders have
      too entered the fray. The situation is complex: Prenatal sex diagnostic tests are
      increasingly available, prospective parents apparently want it. A section of the
      medical profession, which supplies these services, argues that they reflect the
      values of society and are merely meeting the demands of women. It is in this
      context that Amin Malouf's excellent novel 'The Century after Beatrice' should
      perhaps be made essential reading for medical students, indeed all medical
      professionals.

PMID- 12206341
TI  - Research--what is it all about?
AB  - Research is an evolutionary process and being complicated, time-consuming and
      costly one whose end result is never known at the outset. Discovering a new drug
      has been likened to searching for the proverbial needle in a haystack. In test
      tube experiments called assays, compounds are added one at a time to enzymes,
      cell cultures or cellular substances grown in a laboratory. In the search for a
      new cholesterol drug, scientists found a fungus that inhibited the HMG-CoA
      reductase enzyme in a test tube. Chemists then had to identify which of the
      fungus' dozens of chemical by-products was actually inhibiting the enzyme. Once
      that was done, the chemical's structure was analysed and improved on to enhance
      its effects. Research has aimed at discovering what a drug does to the body. If a
      drug's active ingredients don't get into the blood, it won't work. In research
      one has to know when to cut losses if one goes down a wrong way. The role of FDA
      in the early stages of drug research is little. FDA first becomes involved when a
      drug company has completed its testing in animals and is ready to test a drug on
      humans. Drug research is a long, difficult and costly road certainly.

PMID- 12206342
TI  - Bioterrorism--a review.
AB  - With the turn of the new millennium, a new kind of warfare has evolved-
      bioterrorism. After the September 11, 2001 attacks on the World Trade Center,
      every country in the world is now living under the shadow of an unknown yet
      deadly enemy--biological weapons. Every individual has suddenly become very
      vulnerable to this new weapon, which can strike anybody at any time without any
      warning. It is, therefore, important that we take a close look at this new
      weapon, so that we can take appropriate measures to shield ourselves from this
      deadly enemy.

PMID- 12206343
TI  - Compulsory accounts and records maintenance by doctors for saving tax.
AB  - Under the Income-tax Law, it is mandatory on the part of a medical practitioner
      to maintain accounts. Such Books of Accounts and other documents may enable
      theAssessing Officer to compute his total income in accordance withthe provision
      of Income-tax Act, 1961 US/44AA. Rule 6F of the Income-tax Rules, 1962 gives
      details of the Books of Account and other documents. Apart from maintaining the
      Books of Account he is also required to maintain a Daily Case Register in Form No
      3C as also an inventory under broad heads as on the first and last dates of the
      previous year of the stock of drugs and medicines and other consumable
      accessories used for the purpose of his profession.

PMID- 12206344
TI  - Acute intermittent porphyria as a cause of acute respiratory failure.
AB  - A fatal case of acute intermittent porphyria in a 22 years old Indian male is
      reported. He presented with abdominal pain and constipation, subsequently
      developed status epilepticus, acute respiratory failure and quadriparesis. He
      succumbed to the illness on the twelfth day. Among the neuromuscular causes of
      acute respiratory failure, requiring ventilatory support, porphyria is a
      condition potentially treatable, but rarely suspected.

PMID- 12206345
TI  - Urethrorectal fistula by bull horn injury.
AB  - Bull horn injuries are common in rural India. Here one such case causing
      urethrorectal fistula has been reported. The patient was presented with history
      of bull horn injury 6 hours back. He was examined under general anaesthesia and
      found to have lacerations in the anus and anterior wall of rectum. Urgent
      retrograde urethrography and cystography showed partial rupture of bulbar urethra
      and urethrorectal fistula. Initially sigmoid colostomy and suprapubic cystostomy
      was done. Later optical internal urethrotomy was done. The patient was
      catheterised for 3 weeks and the fistula healed completely.

PMID- 12206346
TI  - Ovarian multifoetal pregnancy.
AB  - A 24 years Muslim lady was admitted to SSKM Hospital with the complaint of pain
      lower abdomen, more on left side with ultrasonography diagnosis of alive foetuses
      in a twin pregnancy of 19-20 weeks of gestational age. On the very next day,
      foetal heart sound disappeared with complaint of no foetal movement. Doppler
      study and USG confirmed death of the foetuses. Laparotomy performed 3 weeks after
      foetal death revealed soft bulky uterus of about 10 weeks gestational age. Left
      fallopian tube was found highly stretched over the upper aspect of gestational
      mass and left overy could not be traced. Total hysterectomy with removal of the
      mass and left tube with preservation of right ovary and tube was carried out. On
      pathological examination, the uterus and the gestational mass were found empty
      and separated from the mass. There were two gestational sacs with two separate
      placentae, cords and foetuses of 20 weeks maturity. Microscopic examination
      showed infiltration of ovarian stroma by intermediate trophoblast indicating
      ovarian nidation.

PMID- 12206347
TI  - Our decimating daughters.

PMID- 12206348
TI  - President's tour.

PMID- 12206349
TI  - Female foeticide.

PMID- 12206350
TI  - Needless interventions in medicine.

PMID- 12206351
TI  - Diagnosis and management of foetal nomalies.
AB  - Prenatal diagnosis of foetal anomalies and their management by invasive and non
      invasive techniques are discussed. Early diagnosis allows the parents to organise
      appropriate neonatal management for sublethal and correctable anomalies while
      termination of early pregnancy is an option for lethal anomalies.

PMID- 12206352
TI  - Unusual clinical features of foetal alcohol syndrome.
AB  - Foetal alcohol syndrome (FAS) is a collection of signs and symptoms seen in
      children of women who consume alcohol during pregnancy. With the increasing
      incidence of FAS, there is a great variation of its clinical features different
      from that described in the standard textbooks. This article aims to report on the
      unusual clinical features of FAS. It also aims to explain the mechanism of action
      of alcohol as a teratogenic agent.

PMID- 12206353
TI  - Treatment of thalassoemia--the current scenario.

PMID- 12206354
TI  - Comparative evaluation of functional endoscopic sinus surgery and conventional
      surgery in the management of chronic sinusitis.
AB  - Fifty patients with signs and symptoms of chronic sinusitis and refractory to
      medical treatment constituted this study. They were divided at random into two
      groups of 25 patients each. Group A (study group) patients were subjected to
      functional endoscopic sinus surgery (FESS) and group B (control group) patients
      were treated by conventional surgery. The age of the patients varied from 16-55
      years (mean 29.1). Out of 25 patients in the study group, 19(76%) had complete
      relief of symptoms, 4(16%) had partial relief of symptoms and 2(8%) had no relief
      of symptoms in the follow-up period of 15-33 months (mean 19.2 months). Out of 25
      patients in the control group, 15(60%) had complete relief of symptoms, 4(16%)
      had partial relief of symptoms and 6(24%) had no relief of symptoms in the follow
      up period of 15-33 months (mean 19.2 months). The results of this series revealed
      that FESS had the combined advantages of precise, atraumatic removal of the
      disease with minimal morbidity and at the same time retaining the physiological
      function of the nose and paranasal sinuses.

PMID- 12206355
TI  - Maternal malnutrition, perinatal mortality and foetal pathology--a
      clinicopathological study.
AB  - The close relationship between the maternal malnutrition and consequent birth of
      low birth weight babies and the perinatal mortality is now an accepted fact and
      has been studied extensively in developed countries, though the problem is more
      acute in developing countries. The present study was proposed to find out
      relationship between the maternal nutritional status and the perinatal mortality.
      Autopsy was performed on 100 babies dying perinatally and pathological
      examination of different foetal organs in both well and malnourished mothers was
      also undertaken. Maternal nutritional status was evaluated by estimating
      haemoglobin level and total serum protein level. A mother with haemoglobin level
      below 11 g/dl and/or serum protein level below 5 g/dl was considered as
      malnourished. Pathological findings in the dead babies included low birth weight
      (500-1,999g), haemorrhage in multiple organs, atelectasis of the lungs, fatty
      changes in the liver, cystic changes of the kidneys and ill developed parenchyma
      of the pituitary.

PMID- 12206356
TI  - Asymptomatic haematuria in children.
AB  - Asymptomatic haematuria is not an uncommon problem in children and adolescents.
      Isolated haematuria even when gross is less sinister than haematuria associated
      with proteinuria. Extensive evaluation is usually not necessary in such cases and
      they can generally be followed up after careful evaluation to rule out urinary
      tract infection, hypercalciuria, familial (benign) haematuria, and structural
      abnormalities (cysts, stones, obstruction, Wilms' tumour). Patients with various
      forms of glomerulonephrtis usually have associated proteinuria and may require
      renal biopsy. Intravenous pyelography, cystoscopy and renal angiography should be
      carried out when very clearly indicated.

PMID- 12206357
TI  - Hepatitis C in childhood.
AB  - The prevalence of hepatitis C virus (HCV) infection is relatively low in
      childhood. Blood transfusion has been the principal route of acquisition in
      children but vertical transmission is gradually occupying primacy in the
      developed world. The risk of vertical transmission increases with higher maternal
      viraemia and human immuno-deficiency virus (HIV) co-infection but current
      international guidelines do not suggest avoidance of vaginal delivery and
      breastfeeding to minimise the risk of vertical transmission. The diagnosis of
      perinatal transmission is different from that in older child or adult and
      detection of HCV-RNA is essential. Although the natural history of HCV infection
      in children is not well characterised, almost 50-80% will progress to chronic
      hepatitis among vertically infected and blood transfusion acquired hepatitis C
      cases. Children have a lower viral load, lower ALT values and milder histological
      derangement as compared to adults with chronic hepatitis C cases. Experience of
      treatment of chronic hepatitis C in children is limited and still evolving. Few
      patients achieve spontaneous remission and progression to a more severe liver
      disease might occur in adult life. Here, the natural history, diagnosis and
      management of HCV infection in children are discussed with special emphasis on
      features which are different from adults.

PMID- 12206358
TI  - Serodiagnosis of tuberculosis in children.
AB  - Serodiagnostic tests aid in clinical decision-making process while evaluating
      symptomatic children for active tuberculosis. Interpretation of test results must
      take into consideration the type of antigen used, stage of the disease in the
      child and prevalence of the disease in the population. Epitope specific serology
      and multi-antigen cocktail assays will render acceptable specificity and
      sensitivity to serodiagnostic tests in tuberculosis.

PMID- 12206359
TI  - Polytene chromosomes of Simulium craigi (Diptera: Simuliidae).
AB  - Simulium craigi Adler and Currie is a polymorphic species based on polytene
      chromosome banding patterns in the long arm of chromosome III (IIIL). Three
      cytotypes are described based on the predominant IIIL sequences. These correspond
      to three broad geographic areas: cytotype 'CC' from Pennsylvania; cytotype 'AF'
      from Ontario and Manitoba; and cytotype 'ACF/BCF' from New Hampshire. In the
      absence of sympatric populations, these cytotype differences are best explained
      by clinal variation within a single species. The relationship of S. craigi to
      other described members of the S. vernum group is discussed.

PMID- 12206361
TI  - A comparative cytogenetic study of five piranha species (Serrasalmus,
      Serrasalminae) from the Amazon basin.
AB  - Cytogenetic studies were conducted on five piranha species belonging to the genus
      Serrasalmus, subfamily Serrasalminae (Serrasalmus altispinis, S. compressus, S.
      elongatus, S. manuelli, and S. spilopleura). All the species were collected in
      the Amazon basin: confluence of Negro and Solimoes Rivers (CatalaoLake), Solimoes
      River (Marchantaria Island - Camaleao Lake), Uatuma River (Hydroelectric Power
      Station of Balbina), and Pitinga River (Hydroelectric Power Station of Pitinga).
      All the five species possess 2n = 60 chromosomes with 5-12 subtelo-and
      acrocentric chromosomes bearing nucleolar organizer regions. A proximal C-band
      positive heterochromatin block was evident on the long arms of a medium-sized
      metacentric chromosome pair in all the analized species, thus making it a
      cytogenetic marker for the genus. It is hypothesized that 2n = 60 chromosomes
      represents a derived feature in terms of the chromosomal evolution of piranhas
      because the basal lineages possess 2n = 62. Both Robertsonian centric fusion and
      non-Robertsonian rearragements such as pericentric inversions seem implicated in
      the chromosomal evolution of this group.

PMID- 12206360
TI  - Linkage analysis of quantitative trait loci in multiple line crosses.
AB  - Simple line crosses, for example, backcross and F2, are commonly used in mapping
      quantitative trait loci (QTL). However, these simple crosses are rarely used
      alone in commercial plant breeding; rather, crosses involving multiple inbred
      lines or several simple crosses but connected by shared inbred lines may be
      common in plant breeding. Mapping QTL using crosses of multiple lines is more
      relevant to plant breeding. Unfortunately, current statistical methods and
      computer programs of QTL mapping are all designed for simple line crosses or
      multiple line crosses but under a regular mating system. It is not
      straightforward to extend the existing methods to handle multiple line crosses
      under irregular and complicated mating designs. The major hurdle comes from
      irregular inbreeding, multiple generations, and multiple alleles. In this study,
      we develop a Bayesian method implemented via the Markov chain Monte Carlo (MCMC)
      algorithm for mapping QTL using complicated multiple line crosses. With the MCMC
      algorithm, we are able to draw a complete path of the gene flow from founder
      alleles to their descendents via a recursive process. This has greatly simplified
      the problem caused by irregular mating and inbreeding in the mapping population.
      Adopting the reversible jump MCMC algorithm, we are able to simultaneously search
      for multiple QTL along the genome. We can even infer the posterior distribution
      of the number of QTL, one of the most important parameters in QTL study.
      Application of the new MCMC based QTL mapping procedure is demonstrated using two
      different mating designs. Design I involves two inbred lines and their derived
      F1, F2, and BC populations. Design II is a half-diallel cross involving three
      inbred lines. The two designs appear different, but can be handled with the same
      robust computer program.

PMID- 12206362
TI  - Cytogenetic variability in genus odontocheila (Coleoptera, Cicindelidae):
      karyotypes, C-banding, NORs and localisation of ribosomal genes of O. confusa and
      O. nodicornis.
AB  - Two species of Odontocheila, O. confusa and O. nodicornis, from the Neotropical
      Region were studied regarding their karyotypes, localisation and activity of
      ribosomal genes and C-banding. The species, although belonging to the same genus,
      have quite distinct karyotypes. O. confusa has 10 pairs of autosomes and a single
      sex chromosome mechanism of the XY/XX type, thus a diploid value of 2n = 22 in
      males and females. One aneuploid male with a diploid number of 2n = 20 and one
      male with three B chromosomes were found in a total of eight males studied. O.
      nodicornis has 17 autosomal pairs and also a single chromosome system but of the
      X0/XX type, thus a diploid value of 2n = 35 in males and 2n = 36 in females.
      Fluorescence in situ hybridisation (FISH) revealed the presence of rDNA clusters
      in two autosomes in both species in mitotic and meiotic figures. Silver staining
      of male interphase nuclei confirmed the FISH results and showed that all rDNA
      genes were active. C-banding analysis revealed the presence of constitutive
      heterochromatin in the centromeres of all chromosomes in the two species plus two
      pairs in O. nodicornis with terminal positive C-bands. These results are
      discussed from the cytogenetic and evolutionary point of view.

PMID- 12206363
TI  - Chromosome inversion polymorphisms influence morphological traits in
      Trimerotropis pallidipennis (Orthoptera).
AB  - Trimerotropis pallidipennis is a New World grasshopper whose South-American
      populations are polymorphic for six pericentric inversions. Previous work has
      demonstrated that the frequences of these inversions correlate with climatic
      variables, and hence a possible adaptive pattern was put forward. In the present
      work we analysed a sample of a natural population of T pallidipennis to ascertain
      whether the chromosomal inversions have effects on exophenotypes. Two hundred and
      sixty-eight males coming from a natural population at Uspallata, Mendoza
      Province, Argentina were analysed, and it was observed that most inversions had
      significant effects on phenotypes. Furthermore, some body size-related
      characteristics (such as tegmina length) were correlated with the number of
      inversions. Individuals from populations at higher altitude or latitude (i.e., at
      lower minimum temperatures), along with higher frequencies of standard sequences,
      were significantly smaller, and this coherence between interpopulational with
      intrapopulational results may indicate that the diminished body size of the
      standard sequence-carrying individuals may be caused by an effect of the
      inversions, or genes within the inversions, on body size. We finally put forward
      the hypothesis that reduced body size in a context of reduced minimum temperature
      may be a response to shortened development season, and so smaller individuals may
      be advantageous.

PMID- 12206364
TI  - Description of the cytochrome c oxidase subunit II gene in some genera of New
      World monkeys (primates, Platyrrhini).
AB  - Nucleotide sequence variation at the mitochondrial cytochrome c oxidase subunit
      II gene (COII) was analyzed in 27 New World monkey specimens, nine newly reported
      herein. The study involved comparisons among platyrrhines and also between
      platyrrhines and catarrhines. The analysis of the frequencies of transitions and
      transversions at each codon position showed transitional saturation at third
      codon position. Neighbor-Joining trees obtained from genetic distances estimated
      by means of Kimura's (1980) two-parameter model showed poor resolution of
      phylogenetic relationships among platyrrhine genera. Rates of nucleotide
      substitutions were largely homogeneous except in the genus Saimiri that showed
      low numbers of unique substitutions suggesting the maintenance of ancestral or
      plesiomorphic states of platyrrhine mt DNA nucleotide characters probably due to
      its large population sizes as compared to other platyrrhines.

PMID- 12206365
TI  - Involvement of desat1 gene in the control of Drosophila melanogaster pheromone
      biosynthesis.
AB  - Cuticular pheromones in Drosophila melanogaster are unsaturated hydrocarbons with
      at least one double bond in position 7: 7-tricosene and 7-pentacosene in males
      and 7,11 -heptacosadiene and 7,11 -nonacosadiene in females. We have previously
      shown that a desaturase gene, desat1, located in chromosome region 87 C could be
      involved in this process: the Desat1 enzyme preferentially leads to the synthesis
      of palmitoleic acid, a precursor of omega7 fatty acids and 7-unsaturated
      hydrocarbons. Therefore, we have searched for P-elements in the 87 region and
      mapped them. One was found inserted into the first intron of the desat1 gene.
      Flies heterozygous for this insertion showed a large decrease in the level of 7
      unsaturated hydrocarbons, comparable to that observed in flies heterozygous for a
      deficiency overlapping desat1. Less than 1 % of flies homozygous for this
      insertion were viable. They were characterized by dramatic pheromone decreases.
      After excision of the transposon, the pheromone phenotype was reversed in 69% of
      the lines and the other excision lines had more or less decreased amounts of 7
      unsaturated hydrocarbons. All these results implicate desat1 in the synthesis of
      Drosophila pheromones.

PMID- 12206366
TI  - Chromosome mapping of Miller-Diecker, Smith-Magenis and RARA loci in non-human
      primates: implications in the evolution of human chromosome 17.
AB  - Molecular cytogenetics allows to verify chromosomal homologies previously
      hypothesised on the base of banding pattern comparison in different species. So
      far only the chromosome painting technique has been extensively used in studies
      of chromosomal evolution. This technique allows to detect only interchromosomal
      rearrangements. Human and Great Apes chromosomes basically differ by
      intrachromosomal rearrangements, in particular inversions; with chromosome
      painting it has just been possible to confirm the origin by fusion of human
      chromosome 2 and a reciprocal translocation in Gorilla, involving the homologous
      of chromosome 5 and 17. In order to verify intrachromosomal rearrangements in
      human chromosomal evolution, chromosome mapping of human loci in non-human
      primates is a useful approach. We mapped Miller-Diecker, Smith-Magenis and RARA
      loci localised on human chromosome 17, in Gorilla gorilla, Pongo pygmaeus, Macaca
      fascicularis and Cercopithecus aethiops. On the base of the obtained results it
      was possible to verify chromosomal rearrangements previously identified by
      banding, to achieve new informations about the controversial evolution of human
      chromosome 17, and to detect the occurrence of a paracentric inversion in the
      homologous in Cercopithecus aethiops.

PMID- 12206367
TI  - Hidden evolution: progress and limitations in detecting multifarious natural
      selection.
AB  - From illustrative examples of research on the best-studied group of species to
      date, Drosophila melanogaster and its closest relatives, we argue that selection
      is multifarious, but often hidden. Selective fixation of new, highly advantageous
      alleles is the most parsimonious explanation for a typical pattern of molecular
      variation observed in genomic regions characterized by very low recombination:
      drastically reduced DNA sequence variation within species and typical levels of
      sequence divergence among species. At the same time, the identity of the gene (or
      genes) influenced by selection is not just difficult to discern; it may be
      impossible. Studies of the genetic basis of reproductive isolation demonstrate
      that, although the D. melanogaster complex species appear virtually identical,
      dozens of currently unidentified genes contribute to hybrid sterility. We argue
      that these findings are best explained by selectively-driven functional
      divergence and demonstrate the multifarious nature of selection. Although
      multifarious selection certainly occurs, the exact characters responsible for
      differences in survival and reproductive success are unknown. We do not see these
      inherent limits as a cause for despair or a problem for evolutionary biology.
      Instead, we hope to raise awareness of these complexities of evolution by
      highlighting both the progress and the limitations of characterizing multifarious
      natural selection.

PMID- 12206368
TI  - The Drosophila melanogaster Ku70 coding sequence is wild-type in mus309 mutants.
AB  - Drosophila melanogaster mus309 mutations have been identified as being in the
      Ku70 gene, encoding one subunit of the DNA-dependent protein kinase. However,
      recent work has suggested that these mutations are in the Bloom's syndrome
      homologue. Here, we demonstrate that the coding sequence of Ku70 gene is indeed
      wild-type in two mus309 mutant lines.

PMID- 12206369
TI  - Polio eradication in Australia and the world.

PMID- 12206370
TI  - Australia's notifiable diseases status, 2000. Annual report of the National
      Notifiable Diseases Surveillance System.
AB  - In 2000, there were 89,740 notifications of communicable diseases in Australia
      collected by the National Notifiable Diseases Surveillance System (NNDSS). The
      number of notifications in 2000 was an increase of 5.9 per cent over those
      reported in 1999 (84,743) and the largest reporting year since the NNDSS
      commenced in 1991. Notifications in 2000 consisted of 28,341 bloodborne
      infections (32% of total), 24,319 sexually transmitted infections (27%), 21,303
      gastrointestinal infections (24%), 6,617 vaccine preventable infections (7%),
      6,069 vectorborne infections (7%), 2,121 other bacterial infections
      (legionellosis, meningococcal infection, leprosy and tuberculosis) (2%), 969
      zoonotic infections (1%) and only one case of a quarantinable infection. Steep
      declines in some childhood vaccine preventable diseases such as Haemophilus
      influenzae type b, measles, mumps and rubella, continued in 2000. In contrast,
      notifications of pertussis and legionellosis increased sharply in the year.
      Notifications of bloodborne viral diseases (particularly hepatitis B and
      hepatitis C) and some sexually transmitted infections such as chlamydia, continue
      to increase in Australia. This report also summarises data on communicable
      diseases from other surveillance systems including the Laboratory Virology and
      Serology Surveillance Scheme (LabVISE) and sentinel general practitioner schemes.
      In addition this report comments on other important developments in communicable
      disease control in Australia in 2000.

PMID- 12206371
TI  - Annual report of the National Influenza Surveillance Scheme, 2001.
AB  - Surveillance of influenza in Australia in 2001 was based on data from national
      and state-based sentinel practice consultations for influenza-like illness,
      laboratory isolations of influenza virus and absenteeism rates from a national
      employer. In 2001, laboratory-confirmed influenza became a notifiable disease and
      was reported to the National Notifiable Diseases Surveillance System (NNDSS).
      Influenza A was the dominant type, 81 per cent of which were subtype H1N1 and 19
      per cent were subtype H3N2. The influenza A (H1N1) analysed were all A/New
      Caledonia/20/99-like strains. The H3N2 isolates were antigenically similar to the
      reference strain A/Moscow/10/99 and the vaccine strain A/Panama/2007/99. The
      influenza B isolates, which made up only 10 per cent of all isolates, were mainly
      B/Sichuan/379/99-like strains but 10 per cent of isolates were more closely
      related to B/Harbin/7/94-like viruses, which circulated in previous years. The
      Australian 2001 influenza vaccine represented a good match for the circulating
      viruses and 77 per cent of persons over 65 years in Australia were vaccinated in
      2001.

PMID- 12206372
TI  - Tuberculosis notifications in Australia, 2000.
AB  - Australia has one of the lowest incidences of tuberculosis (TB) in the world. The
      annual incidence rate has remained stable at between 5 and 6 per 100,000
      population, since 1991. In 2000, there were 1,060 TB notifications in Australia,
      of which 1,004 were newly diagnosed cases and 56 were relapse cases. The
      corresponding incidence rate for new and relapsed TB was 5.2 and 0.3 cases per
      100,000 population, respectively. The highest incidence of TB disease in
      Australia continues to be among the overseas-born (18.0 per 100,000 population)
      and Indigenous Australians (15.3 per 100,000 population). By contrast, the
      incidence of disease in the non-indigenous Australian-born population remains low
      (1.2 per 100,000 population).

PMID- 12206373
TI  - Tuberculosis in Australia: bacteriologically confirmed cases and drug resistance,
      2000: report of the Australian Mycobacterium Laboratory Reference Network.
AB  - The Australian Mycobacterium Reference Laboratory Network collected and analysed
      laboratory data on new diagnoses of disease caused by Mycobacterium tuberculosis
      complex in the year 2000. A total of 765 cases were identified, representing an
      annual reporting rate of 4.0 cases of laboratory-confirmed tuberculosis (TB) per
      100,000 population. Pulmonary disease was diagnosed in 64.9 per cent of cases
      with a male:female ratio of 1.5:1. Smears were positive for 209/365 (57.3%) of
      sputum isolates and 39/117 (33.3%) bronchoscopy isolates. Sputum from males was
      more likely to be smear-positive (63.3%) than from females (47.5%). Isolates from
      lymph node accounted for 136 (17.7%) of all cases; only 28.7 per cent were smear
      positive. Eighty-four (11.0%) isolates, comprising 82 M. tuberculosis and 2 M.
      bovis strains, demonstrated in vitro resistance to at least one of the standard
      anti-TB medications. Resistance to at least isoniazid and rifampicin (defined as
      multidrug-resistant TB) was observed for only 8 (1.0%) strains, a rate similar to
      previous years. Almost all (96.3%) of patients with drug resistant strains were
      classified as having initial resistance. The country of birth was known for 76
      (92.7%) of 82 patients with a drug resistant strain of M. tuberculosis; 6 were
      Australian-born and 70 (92.1%) had migrated from a total of 17 countries. Of
      these 70 migrants with drug-resistant disease, 68.6 per cent had migrated from
      one of the following countries: Vietnam (n=15), China (n=11), Philippines (n=11),
      India (n=6), and Indonesia (n=5).

PMID- 12206375
TI  - Towards global polio eradication: Australia's commitment to the global
      eradication of poliovirus by 2005.

PMID- 12206374
TI  - Report on the Second technical advisory group meeting to stop TB in the Western
      Pacific Region, Beijing, China 4-6 June 2001.

PMID- 12206376
TI  - National strategic plan for TB control in Australia beyond 2000.

PMID- 12206377
TI  - Annual report of the Australian Gonococcal Surveillance Programme, 2001.
AB  - The Australian Gonococcal Surveillance Programme monitors the antibiotic
      susceptibility of Neisseria gonorrhoeae isolated in all States and Territories.
      In 2001 the in vitro susceptibility of 3,641 isolates of gonococci from public
      and private sector sources was determined by standardised methods. Antibiotic
      susceptibility patterns again varied considerably between regions. Resistance to
      the penicillins remained high in larger urban centres and warrants close
      attention in those rural centres where treatment with the penicillins continues.
      Quinolone resistance in gonococci (QRNG) became more widespread in Australia in
      2001 and MICs increased. Nationally, 17.5 per cent of all isolates were QRNG.
      Endemic cycles of transmission of QRNG in homosexually active men declined
      further, but heterosexual transmission increased substantially. All isolates
      remained sensitive to spectinomycin. A small number of isolates in a number of
      jurisdictions again showed some decreased susceptibility to ceftriaxone. A high
      proportion of gonococci examined in larger urban centres were from male patients,
      and rectal and pharyngeal isolates were common. In other centres and in rural
      Australia the male to female ratio of cases was lower, and most isolates were
      from the genital tract.

PMID- 12206378
TI  - OzFoodNet: enhancing foodborne disease surveillance across Australia: quarterly
      report, October to December 2001.

PMID- 12206379
TI  - Australia declared polio free.
AB  - For Australia to be declared polio free, evidence of the absence of circulation
      of wild poliovirus was required by the Regional Commission for the Certification
      of Eradication of Poliomyelitis in the Western Pacific in August 2000. Data on
      surveillance of poliomyelitis, acute flaccid paralysis (AFP), vaccine associated
      paralytic polio and enteroviruses were provided to document the absence of
      circulation of wild poliovirus. The last wild poliomyelitis virus case in
      Australia was in 1972. AFP surveillance has improved since it was initiated in
      1995 and achieved a rate of 0.94 per 100,000 population in 1999. No wild
      polioviruses have been isolated from stool samples of AFP cases. Australia has in
      place a comprehensive network of laboratories for enterovirus surveillance and
      this provides further evidence for the absence of wild poliovirus infection. The
      immunisation coverage in the country has been over 80 per cent over the last 3
      years. If there were an importation of a case of poliomyelitis into Australia, a
      national outbreak response would be coordinated through the Communicable Diseases
      Network Australia. Plans for containment of laboratory stocks of wild poliovirus
      are being implemented. The evidence provided was sufficient to satisfy the
      Regional Commission that there was no wild poliovirus circulating in the region
      and enabled Australia to be declared polio free on October 29, 2000 along with
      the other 36 countries in the Western Pacific Region. Australia must remain
      vigilant against importations of wild poliovirus from endemic countries and
      maintain high immunisation coverage and sensitive surveillance systems.

PMID- 12206380
TI  - A large, prolonged outbreak of human calicivirus infection linked to an aged-care
      facility.
AB  - This report investigates an outbreak of acute gastrointestinal illness,
      microbiologically and epidemiologically linked to an aged-care facility and seeks
      to determine if there was a point source of infection. A register of cases that
      included onset date and time of illness and symptoms was maintained by nursing
      staff. Faecal specimens were tested for conventional gastrointestinal pathogens
      and for human calicivirus (HuCV). There were 81 cases reported. Specimens were
      received for testing from 25 cases. Twenty-three of the 25 (92%) specimens were
      positive for HuCV RNA by reverse transcriptase polymerase chain reaction (RT
      PCR). The 2 negative samples contained RT-PCR inhibitors. Descriptive
      epidemiology suggested that staffing practices were important in prolonging the
      outbreak. No point source of infection was identified. Instead environmental
      contamination, aerosol transmission and work practices that fail to take account
      of the natural history of HuCV infection probably contributed to the size (81
      cases) and duration (3 weeks) of this outbreak among the residents, staff and
      visitors of an aged-care facility and their contacts. Institutional outbreaks
      caused by HuCV, formerly called Norwalk-like or small round structured viruses,
      are extremely difficult to control. Infected staff may contribute significantly
      to the amplification of outbreaks. Rapid confirmation of HuCV infection is now
      routinely possible using polymerase chain reaction diagnostics but progress in
      laboratory technology has not yet translated into faster or more effective
      interventions.

PMID- 12206381
TI  - Evaluation of the Australian CJD surveillance system.
AB  - An evaluation of the surveillance capacity of the Australian National Creutzfeldt
      Jakob Disease Registry (ANCJDR) was undertaken. It focused on the ability of the
      Registry to detect CJD in Australia and, in particular, to identify cases that
      require public health responses. The Registry relies on a complex reporting
      system and staff with expertise to accurately identify and classify cases of CJD.
      The Registry satisfies the criteria of flexibility and acceptability and has a
      high positive predictive value and representativeness. The sensitivity of the
      system could not be evaluated, as the rarity of the condition precludes an
      independent assessment of the incidence of CJD, but the incidence of CJD is
      comparable to that found in other countries. The time required to establish a
      definite diagnosis of CJD is approximately 2 months, impacting negatively on the
      timeliness of the system. In order to maximise the likelihood of detecting all
      cases of CJD in Australia in a timely fashion, suggestions are made for improving
      the system's sensitivity and timeliness of reporting as well as for using methods
      that allow meaningful comparisons of incidence between populations with different
      age structures.

PMID- 12206382
TI  - A measles outbreak among young adults in Victoria, February 2001.
AB  - In January 2001 a 19-year-old Sydney resident, who had recently returned from
      India, visited Melbourne for 4 days while infectious with measles. A further 50
      measles cases were subsequently identified, mainly among young adults. Thirty
      eight cases (75%) were in the same birth cohort (born between 1968 and 1981).
      This cohort was identified as being at high risk of measles infection after a
      previous outbreak in Victoria involving 75 cases. These individuals are now aged
      between 20 and 33 years. A high proportion of cases, 22 (43%) were hospitalised
      after multiple visits to various healthcare providers. None of the cases had
      documentation of receiving the recommended number of doses of measles-containing
      vaccine for their age. Repeated outbreaks clearly demonstrate that young adults
      remain the group at highest risk of measles infection in Victoria. More targeted
      strategies for young adults and healthcare workers are required to better protect
      these groups against measles.

PMID- 12206383
TI  - Melioidosis in the Torres Strait islands of far North Queensland.
AB  - During the six-year period from 1995 to 2000, 23 cases of melioidosis were
      diagnosed from the Torres Strait islands that lie between northern Queensland and
      Papua New Guinea. This represents an average annual incidence of 42.7 per 100,000
      population, the highest documented to date in this region. This probably reflects
      the extremely high prevalence of diabetes, the high seasonal rainfall in the
      area, and the lifestyle of Torres Strait Islanders. The majority of patients (20
      out of 23) acquired their disease in one of the more remote outer island
      indigenous communities. Most patients presented with a community-acquired
      pneumonia or with deep seated abscesses. One patient presented with the first
      case of suppurative parotitis due to melioidosis recorded in Australia. Diabetes
      was the overwhelming risk factor, being present in over three-quarters of all
      cases. Five patients (22%) died. Strategies to try to minimise illness and death
      due to melioidosis in the Torres Strait are discussed.

PMID- 12206384
TI  - The National Public Health Partnership.

PMID- 12206385
TI  - Outbreak of gastroenteritis due to Salmonella typhimurium phage type I 35a
      following consumption of raw egg.

PMID- 12206386
TI  - Communicable Diseases Surveillance Highlights for 1st quarter, 2002.

PMID- 12206387
TI  - Magnesium chemistry and biochemistry.

PMID- 12206388
TI  - Structural and catalytic roles for divalent magnesium in nucleic acid
      biochemistry.

PMID- 12206389
TI  - Structural and catalytic chemistry of magnesium-dependent enzymes.

PMID- 12206390
TI  - Determination of [Mg(2+)]i - an update on the use of Mg(2+)-selective electrodes.
AB  - Since their invention, ion-selective microelectrodes have become an indispensable
      tool for investigations of intracellular ion regulation and transport. While
      highly selective sensors for all major intracellular monovalent ions have been
      available for decades, the development of sensors for divalent cations seems to
      have presented more difficulties. As ion-selective microelectrodes typically have
      time-constants in the range of 0.5 to several seconds they turned out to be inapt
      for the investigation of intracellular Ca2+. The development of sensors for Mg2+
      selective electrodes has made its most striking progress only over the past few
      years. While the first Mg2+ sensor, ETH 1117, was barely able to detect
      physiological Mg2+ concentrations in the presence of other mono- and divalent
      cations, the newest sensors allow measurements in the micromolar range. When used
      in macroelectrodes, the most recent developments, ETH 5506 and ETH 5504, have
      even been reported to do so in the presence of millimolar Ca2+ concentrations.
      Although there is still room for improvement to make these sensors applicable in
      microelectrodes, some preliminary data look extremely promising and indicate that
      a new era for Mg2+-selective microelectrodes is about to start.

PMID- 12206391
TI  - Intracellular magnesium and magnesium buffering.
AB  - The development of new techniques for measuring intracellular free Mg2+ during
      the 1980s has provided investigators with the tools needed to produce new
      insights into the regulation of cellular magnesium. Within the limits of this
      technology, it appears that all mammalian cells maintain free cytosolic Mg2+
      levels within the fairly narrow range of 0.25-1 mM. While transport mechanisms
      and sequestration within cellular organelles will contribute to this regulation,
      it is binding of Mg2+ to an as yet poorly defined system of buffers that is
      largely responsible for determining the set point of this regulation. The lack of
      an adequately Mg2+-selective ionophore remains an impediment to progress in this
      area.

PMID- 12206392
TI  - Structure, properties and regulation of magnesium transport proteins.

PMID- 12206393
TI  - Hormonal regulation of Mg2+ transport and homeostasis in eukaryotic cells.

PMID- 12206394
TI  - Mg2+ transport in the kidney.
AB  - Magnesium is abundant in biological systems and an important divalent cation in
      the human body. Mg2+ helps mediate cellular energy metabolism, ribosomal and
      membrane integrity. Additionally Mg2+ modulates the activity of several membrane
      transport and signal transduction systems. Despite its importance however, little
      is known about the molecular mechanisms of Mg2+ transport and homeostasis in
      mammals. In mammals the amount of Mg2+ absorption is about the same as the amount
      of Mg2+ excretion in urine. Additionally, when total Mg2+ intake is deficient,
      the kidney is capable of reabsorbing all filtered Mg2+. This balance between
      intake and excretion indicates that the kidney plays a principal role in
      maintenance of total body Mg2+ homeostasis. Within the kidney, Mg2+ filtered by
      the glomerulus is handled in different ways along the nephron. About 10-20% of
      Mg2+ is reabsorbed by the proximal tubule. the bulk of Mg2+ (about 50-70%) is
      reabsorbed by the cortical thick ascending limb of the loop of Henle. In this
      region, Mg2+ moves across the epithelium through the paracellular pathway, driven
      by the positive lumenal transepithelial voltage. A recently cloned human gene,
      paracellin-1 was shown to encode a protein localized to the tight junctions of
      the cortical thick ascending limb and is thought to mediate Mg2+ transport via
      the paracellular space of this epithelium. The distal convoluted tubule reabsorbs
      the remaining 5-10% of filtered Mg2+. This segment seems to play an important
      role in determining final urinary excretion, since there is no evidence for
      significant Mg2+ absorption beyond the distal tubule. Although many renal Mg2+
      transport activities have been characterized, no Mg2+ transporter cDNAs have been
      cloned from mammalian tissues. Recent research has certainly expanded our
      knowledge of Mg2+ transport in kidney; but details of the transport processes and
      the mechanisms by which they control Mg2+ excretion must await cloning of renal
      Mg2+ transporters and/or channels. Such information would provide new concepts in
      our understanding of renal Mg2+ handling.

PMID- 12206395
TI  - Genetic disorders of magnesium homeostasis.

PMID- 12206396
TI  - Magnesium transport and function in plants: the tip of the iceberg.
AB  - The maintenance of Mg2+ homeostasis in the plant is essential for viability. This
      review describes Mg2+ functions and balancing in plants, with special focus on
      the existing knowledge of the involved transport mechanisms. Mg2+ is essential
      for the function of many cellular enzymes and for the aggregation of ribosomes.
      Mg2+ concentrations also modulate ionic currents across the chloroplast and the
      vacuolar membranes, and might thus regulate ion balance in the cell and stomatal
      opening. The significance of Mg2+ homeostasis has been particularly established
      with regard to Mg2+'s role in photosynthesis. Mg2+ is the central atom of the
      chlorophyll molecule, and fluctuations in its levels in the chloroplast regulate
      the activity of key photosynthetic enzymes. Relatively little is known of the
      proteins mediating Mg2+ uptake and transport in plants. The plant vacuole seem to
      play a key role in Mg2+ homeostasis in plant cells. Physiological and molecular
      evidence indicate that Mg2+ entry to the vacuole is mediated by Mg2+/H+
      exchangers. The Arabidopsis vacuolar Mg2+/H+ exchanger, AtMHX, is highly
      transcribed at the vascular tissue, apparently most abundantly at the xylem
      parenchyma. Inclusion of Mg2+ ions into the vacuoles of this tissue may determine
      their partitioning between the various plant organs. Impacts of Mg2+ imbalance
      are described with respect for both plant physiology and for its nutritional
      value to animal and human.

PMID- 12206397
TI  - Saliva substitutes: how effective and safe are they?

PMID- 12206398
TI  - Deep cervical infections - an uncommon but significant problem.

PMID- 12206399
TI  - The use of gene transfer for the protection and repair of salivary glands.

PMID- 12206400
TI  - The effect of commercially available saliva substitutes on predemineralized
      bovine dentin in vitro.
AB  - OBJECTIVE: The objective of this study was to evaluate the effects of various
      saliva substitutes (Artisial; Glandosane; Oralube; Saliva medac; Oralbalance) on
      the lesion depth and the mineral content of predemineralized bovine dentin in
      vitro. MATERIALS AND METHODS: Ninety-six dentin samples were prepared from 24
      freshly extracted bovine incisors. The samples were predemineralized (pH 5.5; 10
      days), and subsequently exposed to the various artificial salivas. A carbonate
      reduced mineral water (Hirschquelle) as well as the mouthwash solutions Meridol
      and biotene served as controls. Lesion depth and mineral loss were evaluated from
      microradiographs of thin sections (110 microm) by a dedicated software package
      (TMR 1.24). RESULTS: After storage in Glandosane and biotene, the results
      indicated a significant mineral loss and an increase in lesion depth (P < 0.01;
      Wilcoxon). In contrast, specimens stored in Oralube showed a decrease in lesion
      depth and an increase in mineral content (P < 0.05; Wilcoxon). CONCLUSIONS: Thus,
      the use of neither Glandosane nor biotene can be recommended in dentate patients
      with severe xerostomia.

PMID- 12206401
TI  - Impact of lysozyme and lactoferrin on oral Candida isolates exposed to polyene
      antimycotics and fluconazole.
AB  - OBJECTIVE: To assess the antifungal activity of lysozyme and lactoferrin on 10
      oral isolates each of Candida albicans and Candida tropicalis following their
      brief exposure (I h) to subtherapeutic concentrations of two polyene drugs -
      nystatin, amphotericin B, and an azole -fluconazole. METHODS: Yeasts were
      sequentially exposed to subtherapeutic concentrations of antifungals and then to
      either lysozyme or lactoferrin and the viability evaluated by quantifying colony
      forming units. RESULTS: The exposure of both C. albicans and C. tropicalis
      isolates to all three antifungal agents significantly increased their
      susceptibility to lysozyme (P < 0.05) but not to lactoferrin. Exposure to the two
      polyene drugs had a lesser impact on the lysozyme susceptibility of both Candida
      species compared with the azole drug. Both interspecies and intraspecies
      sensitivity to lysozyme was noted and C. albicans was less susceptible than C.
      tropicalis. CONCLUSIONS: Lysozyme, in addition to being a potent natural
      antifungal agent, may act synergistically with the studied antimycotics.

PMID- 12206402
TI  - Bacterial and yeast flora of root surface caries in elderly, ethnic Chinese.
AB  - OBJECTIVES: Root caries is emerging as a significant problem in the middle aged
      and elderly. As little data is available on the microbiology of root caries in
      Chinese cohorts, we evaluated 30 such lesions in elderly, institutionalized,
      ethnic Chinese. METHODS: Samples of carious dentine were aseptically taken from
      root caries lesions of 18 subjects (five males and 13 females, mean age 79.67 +/-
      8.57). The cultivable bacteria, both aerobic and anaerobic, were isolated and
      identified using standard methods and commercial identification kits. The yeasts
      were isolated on Sabouraud's agar and identified using the API system. RESULTS:
      The main findings were: (1) of the total isolates, 91.09% were Gram-positive and
      8.91% were Gram-negative microorganisms; (2) the proportions of cocci and rods
      were 36.68 and 63.31%, respectively; (3) the predominant groups of organisms
      isolated were Streptococcus spp., Lactobacillus spp., Staphylococcus spp. and
      Actinomyces spp. with isolation frequencies of 100, 90.00, 73.33 and 63.33%,
      respectively; (4) the isolation frequency of yeasts belonging to Candida spp.
      (63.33%) was notably high although the proportion of yeasts within each sample
      was low (0.01%). Candida dubliniensis, a newly identified yeast species
      particularly prevalent in HIV infection, comprised 14.29% of yeasts. CONCLUSIONS:
      This study provides baseline information on the microbiologic features of root
      caries in the elderly, ethnic Chinese. Whilst our data on the most predominant
      bacteria isolated in root caries concur with those from other regions of the
      world the isolation of C. dubliniensis from these lesions has not been documented
      before.

PMID- 12206403
TI  - Oral mucosal conditions in elderly dental patients.
AB  - OBJECTIVES: The goals of this study were as follows: to obtain baseline
      information on the incidence of oral mucosal conditions in a population of
      elderly Thai patients and to investigate differences in the presentation of these
      findings in relation to age, sex and the wearing of dentures. SUBJECTS AND
      METHODS: The incidence of oral mucosal conditions was determined by the clinical
      examination of a sample of 500 Thai patients aged 60 years and older. RESULTS:
      The overall incidence of oral mucosal conditions was 83.6% with no significant
      difference between men (81.4%) and women (85%). The incidence of oral mucosal
      conditions indicated a significant increase with advancing age. Varices (59.6%),
      fissured tongue (28%) and traumatic ulcer (15.6%) were the three most common
      conditions; and the incidence increased with age. Leukoplakia and smoker's
      melanosis were more common in men whereas lichen planus was seen more frequently
      in women. Three cases of oral cancer were detected, representing an incidence of
      0.6%. Denture wearers (62.7%) exhibited a significantly higher prevalence of oral
      mucosal conditions than subjects who had no dentures (28.5%) and subjects with
      crowns and/or bridges (8.8%). The three most common denture-related problems were
      traumatic ulcer (22.6%), denture stomatitis (14.3%) and angular cheilitis (4.8%).
      In addition, the incidence of denture-related conditions among complete denture
      wearers (46.3%) was higher than in those wearing partial dentures (40.8%).
      CONCLUSION: The current results regarding an elderly Thai population support the
      studies of other populations whereby the incidence of oral mucosal conditions in
      the elderly is related to age, sex and the wearing of dentures.

PMID- 12206404
TI  - Clostridial deep neck infection developed after extraction of a tooth: a case
      report and review of the literature in Japan.
AB  - A rare case of severe deep neck infection caused by clostridia after extraction
      of the left lower canine is presented. The patient was a 63-year-old Japanese
      woman who had a history of diabetes. The pertinent literature in Japan is
      reviewed and discussed.

PMID- 12206405
TI  - Oncocytic metaplasia in denture hyperplasia. Is it a rare occurrence?

PMID- 12206406
TI  - Underwater sounds near a fuel receiving facility in western Hong Kong: relevance
      to dolphins.
AB  - Western Hong Kong is home to two species of marine mammals: Indo-Pacific
      humpbacked dolphins (Sousa chinensis) and finless porpoises (Neophocaena
      phocaenoides). Both are threatened in many parts of their range in southeast Asia
      [for example, International Biological Research Institute Reports 9 (1997), 41;
      Asian Marine Biology 14 (1997) 111]. In 1998, when the new Hong Kong
      International Airport opened in western Hong Kong, small tankers (about 100 m
      long, cargo capacity about 6300 metric tons) began delivering fuel to the
      Aviation Fuel Receiving Facility (AFRF) just off Sha Chau Island, north of the
      airport. Calibrated sound recordings were taken over a 4-day period from a quiet,
      anchored boat at distances 80-2000 m from aviation fuel delivery activities at
      the AFRF. From the recordings, 143 sections were selected for analysis.
      Narrowband spectral densities on the sound pressures were computed, and one-third
      octave band levels were derived for center frequencies from 10 to 16,000 Hz.
      Broadband levels, viz. 10-20,000 Hz. were also computed. The results showed that
      the Sha Chau area is normally noisy underwater, with the lowest broadband levels
      measured corresponding to those expected during a storm at sea (sea state 6).
      This background noise is believed to come largely from heavy vessel traffic in
      the Urmston Road to the north and east of Sha Chau and from vessels in the Pearl
      River Estuary to the West. The sound levels from the AFRF tankers are comparable
      to the levels measured from similar- and smaller-sized supply vessels supporting
      offshore oil exploration. The strongest sounds recorded were from a tanker
      leaving the AFRF at distance 100 m from the hydrophone, for which the one-third
      octave band level at 100 Hz was 141 dB re 1 microPa (spectrum level 127 dB re 1
      microPa2/Hz) and the 10-20,000 Hz broadband level was 146 dB. At distances of 100
      m or more and frequencies above 300 Hz, the one-third octave band levels were
      less than 130 dB (spectrum level 111 dB re 1 microPa2/Hz) and decreased with
      increasing frequency and distance. At distances greater than about 500 m, AFRF
      associated sounds were negligible, masked by the generally high noise level of
      the area and attenuated by poor transmission in the very shallow water (<10 m).
      Because it is believed that humpbacked dolphins and finless porpoises are not
      very sensitive to sounds below 300 Hz, the Airport Authority Hong Kong (AA)
      stipulated that dedicated terminal vessels not radiate underwater sounds at
      spectrum levels greater than 110 dB re 1 microPa2/Hz at frequencies above 300 Hz
      and distances greater than 300 m. The spectrum levels at 300 Hz and higher
      frequencies of sounds from the tankers arriving, departing, or off-loading at
      AFRF were less than 110 dB re 1 microPa2/Hz even at distances of 200 m or less.
      The AA stipulation was met. However, it is presently unknown whether the
      generally strong noise levels of western Hong Kong inhibit acoustically based
      feeding and communication, or result in increased stress or permanent shifts in
      hearing thresholds.

PMID- 12206407
TI  - Physiological responses to copper in giant clams: a comparison of two methods in
      revealing effects on photosynthesis in zooxanthellae.
AB  - In the present work physiological responses to a short term, sub-lethal exposure
      to copper (5 microg Cu2 l(-1) were studied on two species of giant clams,
      Tridacna gigas and Hippopus hippopus. All giant clams (fam. Tridacnidae) maintain
      a symbiotic relationship with photo-synthesising microalgae (zooxanthellae) and
      the phytotoxic effects of this copper concentration were approached with two
      different end points: changes in oxygen production and maximal quantum yield
      (Fv/Fm). Additionally we measured respiration, whereby Pg:R ratios could be
      calculated for the system (algae and clam) and used as an indicator of stress. Cu
      accumulation was only determined for T. gigas and showed significantly higher
      tissue concentrations in exposed specimens (11.3 microg Cu g(-1) dry wt) compared
      to the controls (4.2 microg Cu g(-1)). Both species displayed significantly
      reduced Pg:R ratios due to exposure, mainly explained by lowered gross
      production. No indication of stress was shown in the fluorescence measurements
      and possible explanations are discussed in the paper. We propose that inhibitions
      in the slow kinetics of photosynthesis were not captured by this fluorescence
      parameter. Accordingly we suggest that measurements of maximum fluorescence yield
      should be accompanied by complementary parameters when studying pollutants with
      unclear phytotoxic mechanisms.

PMID- 12206408
TI  - Bacterioplanktonic abundance, productivity and petroleum hydrocarbon
      biodegradation in marinas and other coastal waters in North Carolina, USA.
AB  - The purpose of this study was to assess the differences in the abundance and
      activity of the bacterioplankton at sites with varied boating activity, and to
      determine the response of the communities to additional petroleum pollution.
      Three sites, including two marinas and a site on Bogue Sound in coastal North
      Carolina, were selected for monthly experiments. Seasonal patterns of
      bacterioplanktonic abundance and diesel fuel biodegradation for each site were
      examined, and possible correlations with intensity of boating activities were
      explored. Bacterioplanktonic communities at the three sites in this study were
      more similar in their structure and biodegradation potential than would have been
      expected from previous studies. We found no differences in the abundance and
      biodegradation potential of theses communities at the three sites, and only a
      slightly elevated number of hydrocarbon degraders at one of the marinas. Patterns
      of biodegradation were more closely related to total bacterial abundance, rather
      than number of petroleum hydrocarbon degraders. There was a strong seasonal
      pattern in bacterial abundance and biodegradation at all three sites. The
      bacterioplanktonic Community at all sites responded similarly to additions of
      diesel fuel. Bacterial abundance and productivity were both elevated to some
      extent, and number of petroleum hydrocarbon degraders changed relatively little.
      These data indicate that marinas may not profoundly after the bacterioplankton
      and that coastal waters often have resident bacterial communities capable of
      degrading petroleum hydrocarbon pollution.

PMID- 12206409
TI  - Cypermethrin induces glutathione S-transferase activity in the shore crab,
      Carcinus maenas.
AB  - Cypermethrin is a synthetic pyrethroid that is particularly toxic to crustacea.
      It is therefore applied as a chemotherapeutant in the salmonid aquaculture
      industry for the treatment of sea lice infestations. After use, cypermethrin is
      released directly into the marine environment, to be diluted by fresh seawater.
      The shore crab, Carcinus maenas is found in the vicinity of fish farms, and may
      come into contact with released cypermethrin. The detoxification enzyme,
      glutathione S-transferase (GST) has been implicated in cypermethrin metabolism in
      terrestrial arthropods, but this has not yet been demonstrated in crustacea. In
      this paper we investigate the response of GST activity in Carcinus to
      cypermethrin exposure, and also the time course of the induction process. GST
      activity is significantly increased in Carcinus exposed to nominal concentrations
      of 50 and 500 ng/l of water-borne cypermethrin. Carcinus demonstrate a
      significant elevation in GST activity following intra-cephalothoracic injection
      with 10 ng of cypermethrin. GST activity returns to basal levels after 36 h. The
      potential application of GST activity in Carcinus as a biomarker of cypermethrin
      exposure is discussed.

PMID- 12206410
TI  - Routes of TBT uptake in the clam Ruditapes decussatus. I. Water and sediments as
      vectors of TBT uptake.
AB  - This study assesses the relative importance of water and sediments as vectors of
      TBT uptake in the sediment-dwelling suspension feeder, Ruditapes decussatus.
      Accumulation of TBT was determined in R. decussatus exposed for 60 days to
      moderately high but environmentally realistic levels of TBT in water (100 ng Snl(
      1)) and sediments (0.8 microg Sn g(-1) dw), separately or in combination, using
      constant-flow systems. The results indicate that this species accumulates TBT
      predominantly from water. Although some accumulation from sediments does occur,
      the processing of large amounts of water needed to sustain the filter-feeding
      habits of this species is a prime determinant of TBT uptake. The route of
      exposures reflected in tissue distributions of TBT in R. decussatus. However,
      gills are the most important site for accumulation of TBT from water,
      irrespective of whether contaminated sediments are present or not.

PMID- 12206411
TI  - Routes of TBT uptake in the clam Ruditapes decussatus. II. Food as vector of TBT
      uptake.
AB  - Marine bivalves are exposed to contaminants via the aqueous phase, sediments and
      food. Nevertheless, the relative importance of these phases as uptake vectors of
      contaminants in these marine organisms has not been well studied. Phytoplankton
      concentrate contaminants from seawater and given their position at the base of
      most marine food webs, these algal cells may play critical roles in the transfer
      of contaminants to higher trophic levels. This study assesses the relative
      importance of microalgae as a vector of tributylin (TBT) uptake in the infaunal,
      suspension-feeding bivalve Ruditapes decussatus. Accumulation of TBT via the
      algal diet was determined by experimental exposure of R. decussatus to 14C-TBT
      labelled phytoplankton Isochrisis galbana, for a period up to 60 days. The
      digestive tract of these clams initially accumulates TBT preferentially from
      food. After a few weeks of exposure, internal remobilization results in a more
      widespread partitioning of TBT amongst tissues.

PMID- 12206412
TI  - Anthropogenic trace metals in sediment and settling particulate matter on a high
      energy continental shelf (Sydney, Australia).
AB  - The anthropogenic contribution of trace metals to settling particulate matter
      (SPM) and surficial sediments was determined on the high-energy continental shelf
      adjacent to Sydney, Australia. Settling particulate matter and surficial sediment
      was collected in the vicinity of a major sewage outfall and at five control sites
      on the middle shelf (80-100 m water depth). Sediment traps were deployed on 10
      occasions for up to 2 weeks during the summer and winter of 1995 and SPM was
      analyzed for Ag, Co, Cr, Cu, Fe, Mn, Ni, Pb and Zn. Cobalt, Fe, Mn and Ni act
      conservatively in SPM and in sediments regionally and are used as normalizing
      elements to determine anthropogenic enrichment. Surficial sediments and SPM are
      enriched in Ag, Cr, Cu, Pb and Zn near a major ocean outfall and at four of the
      five control sites, although sewage particles contribute < 5% of trace metals in
      the total sample. Silver is the most sensitive trace metal tracer for
      establishing the presence of sewage particulate matter. Sewage particulate matter
      flux near the outfall was estimated using a two end-member mixing model and is
      below 0.5 g m(-2) day(-1) during all deployment periods. The mean sewage
      particulate matter flux at sampling locations 30 km and 60 km north of the
      outfall are <0.13 g m(-2) day(-1) and <0.01 g m(-2) day(-1), respectively,
      indicating an efficient dispersal of anthropogenic material on this high energy
      continental shelf.

PMID- 12206413
TI  - Aerobic biodegradation of aliphatic polyethoxylates: an 1H-nuclear magnetic
      resonance spectroscopy investigation.
AB  - Aerobic biodegradation tests of three blends representative of the most commonly
      marketed aliphatic alcohol polyethoxylates (AE) and a commercial polyethylene
      glycols (PEG) mixture were run under standard test conditions (Organization for
      Economic Cooperation and Development, Paris, France [OECD] 301 E protocol). The
      test liquors were investigated using a 400-MHz proton-nuclear magnetic resonance
      (1H-NMR) spectrometer in order to elucidate the biodegradation mechanism.
      Diagnostic signals for both linear and branched AE homologs were identified by
      bidimensional homocorrelated spectroscopy (COSY) and by double quantum filter
      correlated spectroscopy (DQFCOSY). The 1H-NMR allowed individually monitoring the
      fate of the alkyl and polyethoxyl fragments of the parent compounds and
      distinguishing between oxidative and nonoxidative polyethoxyl depolymerization,
      which could not be performed by other reported techniques such as high-peformance
      liquid chromatography (HPLC) or mass spectrometry (MS) or FAB spectroscopy. The
      AE biodegradation time profiles showed that under the test conditions, both alkyl
      and polyethoxyl chains of the linear and oxo-AE were biodegraded quite readily.
      The removal of the multibranched AE was slower when compared to that of linear
      and oxo-AE, while PEG exhibited a time profile characterized by a biodegradation
      rate significantly slower than that of PEG released by the microbial attack of
      linear and oxo-AE. In the case of linear AE, the alkyl chain was biodegraded much
      faster than the polyethoxyl chain, while in the case of oxo- and multibranched
      AE, both the alkyl and the polyethoxyl chains were biodegraded at similar rates.

PMID- 12206414
TI  - Validation of a modified flory-huggins concept for description of hydrophobic
      organic compound sorption on dissolved humic substances.
AB  - Sorption coefficients (K(DOC)) on dissolved organic matter (DOM) have been
      determined by means of solid-phase microextraction (SPME) for hydrophobic organic
      compounds (HOCs) of various classes, for example, polycyclic aromatic
      hydrocarbons (PAHs), noncondensed arenes, and alkanes. Relating the K(DOC) values
      obtained to the octanol-water partition coefficients of the solutes results in
      class-specific correlations. Obviously, PAHs have a higher affinity to DOM than
      other HOCs with equal K(OW) values. The different K(DOC) to K(OW) correlations
      can be combined into one general formula based on a modified Flory-Huggins
      concept. It permits the calculation of sorption coefficients from the solubility
      parameters (delta) and K(OW) values of the solutes and the solubility parameter
      of the sorbent. The latter value, which is specific to the DOM under
      consideration, can be determined from a single measured sorption coefficient. By
      applying the proposed Flory-Huggins concept, which is based on the presumption of
      nonspecific interactions between HOCs and DOM, the different affinities of PAHs,
      noncondensed arenes, and alkanes to DOM can be accurately predicted.

PMID- 12206415
TI  - Trace metal distribution in soluble organic matter from municipal solid waste
      compost determined by size-exclusion chromatography.
AB  - Municipal solid waste (MSW) composts carry high amounts of trace metals and
      organic complexing agents that may influence metal bioavailability and mobility
      after application to soils. In order to assess the degree of organic complexation
      of trace metals in the solution phase of MSW compost and the relevance of organic
      ligand type, size exclusion chromatography (SEC) was applied to compost-extracted
      organic ligands. Adjustment of the elution conditions minimized the interaction
      with the gel matrix for compost humic substances and dissolved organic matter
      (DOM) fractions. The SEC was then used to separate the aqueous compost extract
      into samples with distinct differences in chemical constituents. The highest
      quantities of Cu, Zn, Ni, Mn, and Cd were found to coelute with the main peak of
      the SEC elution curve, which, as observed by Fourier-transformed infrared (FTIR)
      spectroscopy, also had the highest density of carboxyl groups. The ratio of
      aromatic to aliphatic structures was higher for eluates with low retention times,
      and cations such as Al, Cr, and Fe were preferably associated with these larger
      organic molecules. All trace metals in the compost solution phase were bound
      mostly to DOM rather than forming inorganic complexes.

PMID- 12206416
TI  - Comparison of polycyclic aromatic hydrocarbon levels in mussels and oysters in
      France and the United States.
AB  - This paper compares data of 15 individual polycyclic aromatic hydrocarbon (PAH)
      concentrations from two monitoring programs: the French Rdseau National
      d'Observation de la qualite du milieu marin (RNO) and the Mussel Watch project of
      the U.S. National Status and Trends (NST) program. Polycyclic aromatic
      hydrocarbon measurements in bivalve (mussels and oysters) are made from samples
      collected at 265 sites along the U.S. coastline and at 97 sites in the French
      coastal waters. Individual PAH patterns were found strikingly similar between the
      two countries with higher concentrations for high-molecular-weight (HMW) PAHs.
      Principal component analysis results for both RNO and NST show the variability to
      be dominated by just two components with HMW compounds contributing primarily to
      the first and low-molecular-weight (LMW) compounds to the second. This could
      imply a separation of petrogenic and pyrolytic sources with the latter being the
      more important in both nations accounting for the similarity in results.

PMID- 12206417
TI  - Use of anodic stripping voltammetry in predicting toxicity of copper in river
      water.
AB  - The labile concentration and toxicity of Cu as influenced by alkalinity and
      different concentrations of ethylenediaminetetraacetic acid (EDTA) and naturally
      derived fulvic acid (FA) were determined by bioassays carried out in the culture
      media for Daphnia magna (D. magna). The labile concentration of Cu was obtained
      by differential pulse anodic stripping voltammetry with a double-acidification
      method (DAM-DPASV). Changes in water alkalinity did not affect the labile
      concentration of Cu, but increase in alkalinity did reduce the mortality of D.
      magna. In the presence of EDTA and FA, both labile concentration of Cu and
      mortality were reduced. By excluding Cu-carbonate complexes from the labile
      concentration, a bioavailable concentration of Cu ([Cu*]) was obtained and was
      used to predict the acute toxicity of Cu on D. magna. For natural waters, the
      labile concentration of Cu was measured by DAM-DPASV, and [Cu*] was calculated
      using MINTEQ A2 software (developed by the U.S. Environmental Protection Agency)
      based on the anion composition of waters. This procedure was tested for waters
      and sediment elutriates sampled from the Le An River (Jiangxi Province, China)
      that were severely polluted by the discharges from a copper mine. The results
      showed that [Cu*] was a good indicator for Cu toxicity and could be used under
      field conditions.

PMID- 12206418
TI  - Analysis of trace organic contaminants in sediment, pore water, and water samples
      from Onsan Bay, Korea: instrumental analysis and in vitro gene expression assay.
AB  - Persistent organic pollutants and alkylphenols (APs) were determined in sediment
      and water samples from Onsan Bay, Korea, by using instrumental analysis and in
      vitro gene expression cell bioassay. Polycyclic aromatic hydrocabons (PAHs) were
      the predominant compounds in sediments with concentrations as great as 573 ng/g
      dry weight. The PAH concentrations were elevated in sediment from inland rivers
      that flow through Onsan City (mean: 116 ng/g dry wt) and discharge into Onsan
      Bay. Concentrations of polychlorinated biphenyls (PCBs) in sediments ranged from
      <1.00 to 56.2 ng/g dry weight. Among different organochlorine (OC) pesticides
      analyzed (hexachlorobenzene, hexachlorocyclohexanes, chlordanes, and DDTs), DDT
      concentrations were the greatest, ranging from <0.01 to 7.58 ng/g dry weight. The
      spatial gradient of contaminant concentrations suggested that streams and rivers
      are the major sources of PCBs, PAHs, and APs to the bay. Maximum concentrations
      of nonylphenol, octylphenol, and bisphenol A in sediments were 860, 11, and 204
      ng/g dry weight, respectively. Screening of Onsan Bay sediment samples for
      dioxinlike activity with the H4IIE-luc in vitro cell bioassay revealed that 17 of
      22 samples contained significant dioxinlike activity. Further fractionation of
      sediment extracts indicated that mid-polar and more polar fractions were
      responsible for the significant dioxinlike activity. Based on a mass balance
      analysis, PAHs apparently accounted for only a small portion of dioxinlike
      responses elicited by sediment extracts. Only one raw extract of sediment
      elicited a significant estrogenic response by MVLN cells. The combination of
      instrumental analysis and in vitro bioassay was useful to assess sediment quality
      and characterize the causative agents or potential toxic compounds present.

PMID- 12206419
TI  - Vapor pressures, aqueous solubilities, and Henry's law constants of some
      brominated flame retardants.
AB  - The subcooled liquid vapor pressures (P0(L),25S) and aqueous solubilities
      (Sw,25s) were determined and Henry's law constants (H25s) were estimated for a
      number of brominated flame retardants (BFRs) at 25 degrees C. The established
      methods of the gas chromatography-retention time and generator column techniques
      were used to experimentally determine P0(L),25 and Sw,25 for hexabromobenzene and
      a series of brominated diphenyl ether (BDE) congeners. The H25 was estimated as
      the ratio of P0(L)25 to the subcooled liquid aqueous solubility. Values of
      PL0(L),25 obtained ranged from 0.000000282 Pa (BDE-190) to 0.259 Pa (BDE-3);
      Sw,25 ranged from 0.00000087 g/L (BDE-153 and BDE-154) to 0.00013 g/L (BDE-15);
      and H25 ranged from 0.0074 Pa m3/mol (BDE-183) to 21 Pa m3/mol (BDE-15). An
      increase in the bromine content of polybrominated diphenyl ether congeners
      resulted in significant decreases Of P0(L),25, Sw25, and H25. A simple four
      compartment equilibrium distribution model suggested that the majority of BFRs
      being released into the environment would reside in soil and sediment and have
      localized distributions. The model also suggested that lower brominated congeners
      tend to be somewhat more mobile. Degradative debromination reactions that yield
      these congeners would mobilize them environmentally, and ultimately affect the
      fate and distribution of BFRs.

PMID- 12206420
TI  - Environmental cadmium induces histopathological changes in kidneys of roe deer.
AB  - Kidney samples of 224 roe deer (113 males, 111 females) aged three months to
      approximately nine years were collected in eastern Austria. Cadmium contents were
      examined and histological examinations were performed considering 11 different
      pathomorphological parameters. Cadmium burden was relatively high (range: 0.010
      22.076 ppm) and increased with age. Females aged one to two years had higher
      contents than males of the same age. The culling site had no influence on cadmium
      load. The relation between the occurrence of histopathological changes and age,
      sex, origin, and cadmium concentration in 208 roe deer was tested. The frequency
      of vacuolic degeneration, pycnotic nuclei, caryolysis, and necrosis was related
      to increased cadmium levels. Increasing age correlated with lymphohistiocytic
      infiltration, interstitial fibrosis, and swelling of glomeruli. Pigment deposits
      and thickening of Bowman's capsule could be related to both cadmium and age.
      Furthermore, roe deer from an industrialized region showed alterations more
      frequently than animals from rural areas. We found no relation between
      morphological changes and sex. Though it remains to be established whether
      environmental cadmium exposure is the sole cause for the histopathological
      alterations observed, the results of this study indicate that chronic cadmium
      poisoning may be an important cofactor in the pathogenic mechanisms of renal
      damage in roe deer and that cadmium intoxication may be more widespread among
      wildlife than previously known.

PMID- 12206421
TI  - Uptake and loss of chlorpyrifos and atrazine by Juncus effusus l. in a mesocosm
      study with a mixture of pesticides.
AB  - Abstract-Aquatic organisms in agricultural regions typically are exposed to
      mixtures of agrochemicals, and effects are not adequately predicted from results
      of single pesticide exposure studies. Thus, a mesocosm study was designed to
      examine the fate and effects of varying mixtures of three pesticides
      (chlorpyrifos, atrazine, and monosodium methanearsonate) and mercury-contaminated
      sediment to the common freshwater macrophyte Juncus effusus L. Exposure doses of
      pesticides added to mesocosms represented those that might be encountered in a
      typical runoff or direct spray application. This study reports the uptake and
      loss of chlorpyrifos and atrazine in the leaves of J. effusus after a single and
      a repeated dose of the chemical mixture over 94 d. The measured chlorpyrifos
      levels in leaves were highest on day 1, but levels in both leaves and water
      dropped rapidly and were at background levels by day 32. Atrazine remained near
      nominal concentrations in the water through day 16 and reached maximum
      accumulation in the leaves on day 16. The chemical mixture affected uptake of
      chlorpyrifos more strongly than atrazine as measured by differences in uptake
      variability. After the second dose, J. effusus showed a similar uptake pattern
      for both compounds, although somewhat faster, to that observed after the first
      dose, with no diminished capacity for uptake of either compound. The greater
      volatility of chlorpyrifos, the higher solubility of atrazine, and the more
      efficient transport of atrazine to the root zone are characteristics that are
      consistent with the differences observed in their uptake and loss behavior.

PMID- 12206422
TI  - Biochemical effects of chlorpyrifos on two developmental stages of Xenopus
      laevis.
AB  - Abstract-The effects of a 96-h static exposure to chlorpyrifos were examined in
      two developmental stages of larval Xenopus laevis (premetamorph and metamorph).
      Measures of effect included mortality, deformity, cholinesterase (ChE) activity,
      and DNA and protein concentration. All parameters indicated that metamorphs were
      more sensitive than were premetamorphs. For larvae exposed as premetamorphs, the
      median lethal concentration and median effective concentration were 14.6 mg/L and
      1.71 mg/L; for those exposed as metamorphs, values were 0.56 mg/L and 0.24 mg/L,
      respectively. Cholinesterase activity was the most sensitive biochemical
      parameter. Exposure to chlorpyrifos at 0.01 mg/L caused significant decreases in
      the ChE activity of metamorphs; 0.1 mg/L significantly decreased premetamorph ChE
      activity. Metamorph DNA was significantly decreased at 0.1 mg/L; premetamorph DNA
      was not reduced until exposure to 1.0 mg/L. Whole-body protein was the least
      sensitive biochemical measure of effect. Premetamorphs did not experience a
      reduction in protein concentrations. Metamorph protein concentration was
      significantly decreased at 1.0 mg/L. Based on current surface water data, the
      most sensitive effect would not have a high probability (< or = 4.2%) of
      occurring in the environment.

PMID- 12206423
TI  - Cadmium-induced production of a metallothioneinlike protein in Tubifex tubifex
      (Oligochaeta) and Chironomus riparius (Diptera): correlation with reproduction
      and growth.
AB  - Laboratory-cultured Chironomus riparius and Tubifex tubifex were exposed to
      sediments artificially enriched with a range of cadmium (Cd) concentrations. Both
      species accumulated Cd in a concentration-dependent manner. The concentration of
      a metallothioneinlike protein (MTLP), as measured by a mercury saturation assay,
      increased with increasing Cd exposure. After reaching a threshold of Cd exposure,
      the whole-body endpoints of reproductive output in T. tubifex and growth in C.
      riparius declined significantly. The threshold effect concentrations for T.
      tubifex and C. riparius were 2.68 and 0.134 micromol Cd/g dry sediment,
      respectively. Metallothioneinlike protein and Cd tissue concentrations were more
      sensitive indicators of exposure than the whole-body endpoints. For T. tubifex,
      the concentrations of MTLP and tissue Cd were significantly elevated above
      control levels after exposure to the 0.67 micromol Cd/g dry sediment treatment.
      In C. riparius, MTLP concentration and tissue Cd concentration were both
      significantly elevated above control levels after exposure to the 3.8 x 10(-3)
      micromol Cd/g dry sediment treatment. Analysis of these data suggests that MTLP
      and tissue Cd concentrations are sensitive subcellular endpoints, which can be
      used to predict exposure to and the effects of metals at the individual or
      population level.

PMID- 12206424
TI  - Altering cytochrome P4501A activity affects polycyclic aromatic hydrocarbon
      metabolism and toxicity in rainbow trout (Oncorhynchus mykiss).
AB  - The polycyclic aromatic hydrocarbons (PAHs) phenanthrene and retene (7-isopropyl
      1-methyl phenanthrene) are lethal to rainbow trout (Oncorhynchus mykiss) larvae
      during chronic exposures. Phenanthrene is a low-toxicity, non-cytochrome P4501A
      (CYP1A)-inducing compound that accumulates in fish tissues during exposure to
      lethal concentrations in water. Retene is a higher toxicity CYP1A-inducing
      compound that is not detectable in tissue at lethal exposure concentrations. The
      metabolism, excretion, and toxicity of retene and phenanthrene were examined in
      juvenile and larval rainbow trout during coexposure to the model CYP1A inducer
      beta-naphthoflavone (betaNF), or to the inducer-inhibitor piperonyl butoxide to
      determine if modulating CYP1A activity affected PAH metabolism and toxicity.
      Phenanthrene metabolism, excretion rate, and toxicity increased with coexposure
      to betaNE Piperonyl butoxide inhibited phenanthrene metabolism and reduced the
      excretion of all phenanthrene metabolites. As a consequence, embryo mortality
      rates increased but rates of sublethal effects did not. Coexposure of trout to
      retene and betaNF caused no change in retene metabolism and excretion, but retene
      toxicity increased, perhaps due to additivity. Piperonyl butoxide inhibited
      retene metabolism, decreased the excretion of some retene metabolites while
      increasing the excretion of others, and increased the toxicity of retene. These
      results support the role of CYP1A activity in PAH metabolism and excretion, and
      the role ofthe CYP1A-generatedmetabolites of PAHs in chronic toxicity to larval
      fish.

PMID- 12206425
TI  - Response of macroinvertebrates to copper and zinc in a stream mesocosm.
AB  - Metal pollution of streams and rivers is recognized as one of the major concerns
      for management of freshwaters. Macroinvertebrate communities were established
      within 12 artificial streams and exposed to three replicated concentrations of a
      metals mixture (copper and zinc) for 34 d. The cumulative criterion units (CCU =
      sigma[metals]/hardness-adjusted U.S. Environmental Protection Agency [U.S. EPA]
      1996 chronic criterion value) of total metals in the low, medium, and high
      treatments were 2.4, 5.9, and 18 CCUs. Zinc comprised approximately 75% of the
      CCUs in each of the treatments. Effects on taxa richness and the number of taxa
      in the orders Ephemeroptera, Plecoptera, and Trichoptera (EPT) were moderate at
      the high exposure concentration (-23% and -26% respectively, p < 0.05). All of
      the five major mayfly species showed near extinction, whereas four of the seven
      caddisflies showed stimulation (up to +121%) and three were reduced (up to -76%).
      Redundancy analysis for this metal gradient indicated that 94% of the variance in
      community structure was explained by three quantitative variables: total mayfly
      abundance, a mollusk (Potamopyrgus antipodarum) abundance, and the number of EPT
      individuals, indicating that multiple indices do provide improved predictors of
      metal stress. Most species showed a threshold response relationship, whereas some
      community indicators showed apparent hormetic responses (e.g., number of mayfly
      taxa, total taxa, and number of EPT taxa). Model concentration-response
      relationships with generalized linear models were used to provide threshold of
      20% effective concentration values for species and community metrics. Threshold
      effect values ranged upwards of 1.4 CCUs, indicating that U.S. EPA chronic
      criteria would be protective of species and community responses.

PMID- 12206426
TI  - Development of a fish reporter gene system for the assessment of estrogenic
      compounds and sewage treatment plant effluents.
AB  - This study reports on the development and application of a fish-specific estrogen
      responsive reporter gene assay. The assay is based on the rainbow trout
      (Oncorhynchus mykiss) gonad cell line RTG-2 in which an acute estrogenic response
      is created by cotransfecting cultures with an expression vector containing
      rainbow trout estrogen receptor a complementary DNA (rtERalpha cDNA) in the
      presence of an estrogen-dependent reporter plasmid and an estrogen receptor (ER)
      agonist. In a further approach, RTG-2 cells were stably transfected with the
      rtERalpha cDNA expression vector, and clones responsive to 17beta-estradiol (E2)
      were selected. The estrogenic activity of E2, 17alpha-ethinylestradiol, 4
      nonylphenol, nonylphenoxy acetic acid, 4-tert-octylphenol, bisphenol A, o,p'-DDT,
      p,p'-DDT, o,p'-2,2-bis(chlorophenyl)-1,1-dichloroethylene (o,p'-DDE), p,p'-DDE,
      o,p'-2,2-bis(chlorophenyl)-1,1-di-chloroethane (o,p'-DDD), p,p'-DDD, and p,p'-2,2
      bis(chlorophenyl)acetic acid (p,p'-DDA) was assessed at increasing
      concentrations. All compounds except o,p'-DDT, p,p'-DDE, and p,p'-DDA showed
      logistic dose-response curves, which allowed the calculation of lowest-observed
      effect concentrations and the concentrations at which half-maximal reporter gene
      activities were reached. To check whether estrogen-responsive RTG-2 cells may be
      used to detect the estrogenic activity of environmental samples, an extract from
      a sewage treatment plant (STP) effluent was assessed and found to have estrogenic
      activity corresponding to the transcriptional activity elicited by 0.05 nM of E2.
      Dose-response curves of nonylphenol, octylphenol, bisphenol A, and o,p'-DDD
      revealed that the RTG-2 reporter gene assay is more sensitive for these compounds
      when compared to transfection systems recombinant for mammalian ERs. These
      differences may have an effect on the calculation of E2 equivalents when
      estrogenic mixtures of known constitution, or environmental samples, such as STP
      effluents, are assessed.

PMID- 12206427
TI  - Nonylphenol polyethoxylate adjuvant mitigates the reproductive toxicity of
      fomesafen on the freshwater snail Lymnaea stagnalis in outdoor experimental
      ponds.
AB  - The influence of nonylphenol polyethoxylates (NPEO), formulated as the adjuvant
      Agral 90, on the effects of the diphenyl ether herbicide fomesafen in the pond
      snail Lymnaea stagnalis was investigated, with particular attention to the
      reproductive performances and underlying energetic and hormonal processes.
      Separate short-term exposures to low concentrations of fomesafen and fomesafen
      Agral mixture were performed in the laboratory. Outdoor experimental ponds
      (mesocosms) were used for long-term exposures to higher chemical concentrations.
      At the concentrations used in the studies, NPEO were known as nontoxic in L
      stagnalis. Fomesafen was mixed with the adjuvant in the 3:7 ratio recommended for
      agricultural uses (nominal herbicide concentrations of 22 and 40 microg/L in
      laboratory and mesocosm, respectively). In mesocosms, multiple application of
      fomesafen, leading to maximal herbicide concentrations of 60.33 +/- 2.68 microg/L
      in water, resulted in reduced number of egg masses and altered glycogen
      metabolism in contaminated snails. These changes, as well as affected steroid
      like levels in fomesafen-exposed snails, support the hypothesis of impaired
      neuroendocrine functions. When Agral 90 was added to the herbicide, results
      obtained in mesocosms showed that the adjuvant softened the impact of fomesafen.
      In mesocosms treated with the fomesafen-Agral mixture, significantly lower
      herbicide levels were found in the water (30.33 +/- 14.91 microg/L at the end of
      the contamination period). Consequently, internal exposure of the snails to
      fomesafen was reduced when the herbicide was mixed with the adjuvant. Mitigation
      of the effects of fomesafen by the adjuvant may therefore result from nonionic
      surfactant activity of NPEO that prevented fomesafen from reaching the snails.

PMID- 12206428
TI  - Transplanted zebra mussels (Dreissena polymorpha) as active biomonitors in an
      effluent-dominated river.
AB  - For over 20 years, mussels have been recommended as one of the most suitable
      biomonitoring organisms for aquatic ecosystems. Though the common mussel (Mytilus
      edulis) is frequently used for biomonitoring estuarine and marine ecosystems, no
      freshwater species is promoted for similar monitoring networks. Recently,
      however, the zebra mussel (Dreissena polymorpha) has been proposed as a suitable
      monitoring organism in freshwater ecosystems. The aim of this study was to
      explore the usefulness of transplanted zebra mussels as active biomonitors in an
      effluent-dominated stream. Results showed that for these purposes, an exposure
      period of at least a few weeks is required to detect any significant changes in
      condition status or scope for growth. Wet-tissue-weight:dry-tissue-weight ratio
      was the most sensitive measure to quantify effects of field exposure on
      physiological fitness. In case of scope for growth (SfG), energy intake was the
      factor determining the overall energy budget of the mussels. Based on the
      dilution rates of the two different effluents present, effluent 2 had the most
      important effect on the condition status of the exposed organisms. Overall, we
      conclude that the use of transplanted mussels is a sensitive and easily
      applicable active biomonitor that can be used to assess water quality, pollution,
      and subsequent recovery through self-purification in field situations.

PMID- 12206429
TI  - Fish (Fundulus heteroclitus) populations with different exposure histories differ
      in tolerance of creosote-contaminated sediments.
AB  - Prior studies suggest that field-collected fish (Fundulus heteroclitus) from a
      creosote-contaminated Superfund site (Atlantic Wood Industries site, Elizabeth
      River, VA, USA) have enhanced tolerance to local, contaminated sediments. This
      study was designed to test whether other populations in the Elizabeth River at
      less contaminated sites also show similar tolerance and whether this tolerance is
      heritable. To test this, F. heteroclitus populations were sampled from four sites
      within the Elizabeth River with varying sediment polycyclic aromatic hydrocarbon
      (PAH) concentrations (3.9-264 ng PAH/g dry wt 10(3)) and one reference site in a
      nearby, uncontaminated estuary (York River, VA, USA; 0.27 ng PAH/g dry wt x
      10(3)). Embryo assays were performed to quantify population differences in
      teratogenic effects during contaminated sediment exposure. Atlantic Wood sediment
      was mixed with reference sediment to achieve a range of sediment concentrations.
      Minimal differences were observed in teratogenic effects among fish taken from
      sites within the Elizabeth River; however, embryos of fish collected from a
      nearby, uncontaminated York River site and exposed to contaminated sediments had
      a significantly higher proportion of embryos with cardiac abnormalities than
      those from the Elizabeth River sites. Embryos from wild-caught and laboratory
      reared Elizabeth River F. heteroclitus were simultaneously exposed to
      contaminated sediments, and no significant tolerance differences were found
      between embryos from fish taken directly from the field and those reared for a
      generation in the lab. Differences between fish populations from the two
      estuaries were larger than differences within the Elizabeth River, and these
      differences in tolerance were heritable.

PMID- 12206430
TI  - Demographic responses of the polychaete Dinophilus gyrociliatus to chromium
      exposure.
AB  - The effects of chromium on the life history and demography of Dinophilus
      gyrociliatus (Polychaeta) were studied on a control and three treated cohorts
      kept in artificial seawater enriched with nominal concentrations of chromium at
      1.0, 1.4, and 1.6 microg/ml. Survival and fecundity were significantly reduced by
      chromium. Fecundity was higher in the chromium treatments than in the control
      group at the beginning of the reproductive period; however, overall, the highest
      fecundity was observed in the control. Life expectancy, net growth rate, and
      generation time were also significantly reduced by chromium. The population
      growth rate (lambda) was higher in the treated animals than in the controls. The
      differences in lambda between the treated animals and the controls (deltalambda)
      were almost completely due to the differences in the life tables observed during
      the first three weeks of life. The differences in survival between the treated
      and control animals did not contribute to deltalambda. The contribution to
      deltalambda of the slight increase in age-specific fecundity in the early
      reproductive events compensated for the marked decrease in overall fecundity in
      the treated animals. The complex effects of chromium enrichment on D.
      gyrociliatus underline the importance of analyzing both individual and population
      responses when assessing the effects of pollutants on organisms. Our results
      confirm that D. gyrociliatus might serve as an indicator species in confined
      areas of polluted seawater such as lagoons and harbors.

PMID- 12206431
TI  - Polychlorinated dibenzo-p-dioxins and dibenzofurans and dioxinlike
      polychlorinated biphenyls in sediments and mussels at three sites in the lower
      Great Lakes, North America.
AB  - Levels of contaminants including polychlorinated dibenzo-p-dioxins (PCDDs),
      polychlorinated dibenzofurans (PCDFs), non-ortho-substituted and mono-ortho
      substituted dioxinlike polychlorinated biphenyls (DLPCBs) were determined in
      sediments and freshwater mussels (Dreissena spp. and Elliptio complanata) at
      three sites in the lower Great Lakes (North America). Impacts of mussel
      colonization on sediment quality were investigated by comparing contaminant
      levels in colonized sediment with levels in sediment in the same area that was
      not colonized, but exposed to similar environmental conditions. Significant
      impacts on contaminant levels of colonized sediment, compared to noncolonized
      sediment, were observed at two sites exhibiting high mussel population densities
      (Fort Erie, eastern Lake Erie, ON, Canada, 2.2 kg/m2 dry wt biomass, and Port
      Dalhousie, western Lake Ontario, Ontario, Canada, 6.1 kg/m2 dry wt biomass);
      these differences were not observed at a site with lower mussel densities (Bay of
      Quinte, eastern Lake Ontario, Ontario, Canada, 0.7 kg/m2). Total organic carbon
      and contaminant concentrations were statistically significantly greater in
      colonized sediment, compared to noncolonized sediment, at the two impacted sites.
      Areal estimates of PCDD/PCDF and DLPCB toxicity equivalents (TEQs) in mussel
      biomass at the three sites averaged 0.16% and 3.3%, respectively, of the TEQs in
      the top 3 cm of sediment, indicating that the sediments were the primary sink for
      contaminants. The observed differences between colonized and noncolonized
      sediment suggest that Dreissena are capable of influencing the chemical
      properties of sediment they colonize.

PMID- 12206432
TI  - Acute and chronic toxicity of zinc to the mottled sculpin Cottus bairdi.
AB  - The acute and chronic toxicity of zinc to wild mottled sculpin (Cottus bairdi)
      was measured with 13-d and 30-d flow-through toxicity tests, respectively.
      Exposure water hardness was 48.6 mg/L as CaCO3 and 46.3 mg/L as CaCO3 in the
      acute and chronic tests, respectively; pH was slightly above neutral; and
      temperature near 12 degrees C. The median lethal concentration (LC50) after 96 h
      was 156 microg Zn/L, but decreased with exposure duration to a median incipient
      lethal level (ILL50) of 38 microg Zn/L after 9 d, the lowest zinc LC50 reported
      for any fish species. The 30-d chronic no-effect and lowest-effect concentrations
      were 16 microg Zn/L (no mortality) and 27 microg Zn/L (32% mortality),
      respectively. The ILL50 was 32 microg Zn/L. No sublethal growth differences were
      observed during the chronic test. Analysis of the results from these tests
      suggested that mottled sculpin may experience acute and chronic toxicity at zinc
      concentrations lower than any other fish species tested to date. Protection of
      aquatic communities in stream reaches contaminated by metals seem to require
      determination of zinc toxicity to lotic species other than trout and other
      species amenable to aquaculture.

PMID- 12206433
TI  - Relative sensitivity of three terrestrial invertebrate tests to polycyclic
      aromatic compounds.
AB  - In a project investigating the ecotoxicity of polycyclic aromatic compounds
      (PACs), we have previously reported on the sublethal toxicity of eight PACs to
      springtails (Folsomia fimetaria) and enchytraeids (Enchytraeus crypticus). The
      model substances included four polycyclic aromatic hydrocarbons (PAHs) and four N
      S-O-heterocyclics. Here, new data are presented on the effects of PACs on the
      survival and growth of the earthworm Eisenia veneta, showing that, in general,
      earthworm growth was reduced at PAC concentrations above 25 mg/kg soil dry
      weight. The E. veneta tests were performed using the same soil type and very
      similar test conditions as for the F. fimetaria and E. crypticus tests, thus
      providing a good opportunity to compare the sensitivity of these three organisms.
      Species sensitivity was examined using the 50% reduction in survival (LC50
      values) and no-observable-effect concentrations (NOEC values) for growth or
      reproduction as endpoints. The difference between the least and most sensitive
      species was generally much larger for LC50 values as compared to the NOEC values,
      suggesting a higher degree of uncertainty when extrapolating from one species to
      another for the LC50 data. For the NOEC data, relatively small differences in
      sensitivity was observed, but as a rather consistent pattern, F. fimetaria was
      the most sensitive and E. crypticus the least sensitive species. However, one
      substance (acridine) showed specific toxicity toward E. veneta, which was more
      sensitive than the two other species by more than one order of magnitude.

PMID- 12206434
TI  - Accumulation of heavy metals in water spinach (Ipomoea aquatica) cultivated in
      the Bangkok region, Thailand.
AB  - The aquatic plant water spinach (Ipomoea aquatica), either wild or cultivated, is
      found throughout Southeast Asia and is a widely consumed vegetable in the region.
      Many of the waters where I. aquatica grows serve as recipients for domestic and
      other types of wastewater. Because these waters contain not only nutrients, but
      often also a wide variety of pollutants such as heavy metals from various human
      activities, many people risk intoxication. To estimate the accumulation of lead
      (Pb), cadmium (Cd), total mercury (total Hg), and methylmercury in I. aquatica
      and the potential hazard to human health via consumption, nine sites for
      cultivation of I. aquatica in the greater Bangkok region of Thailand were
      sampled. At seven of the sites, I. aquatica was cultivated for the local food
      market. The concentrations of methylmercury, total Hg, Pb, and Cd in I. aquatica
      were 0.8 to 221, 12 to 2,590, 40 to 530, and < or = 10 to 123 microg/kg dry
      weight, respectively. At all sites at least one element showed relatively high
      concentrations and no reference site could be established. From threshold values
      for highest tolerable intake of these metals by humans and information about
      consumption of I. aquatica among local people, Pb and Cd concentrations in I.
      aquatica do not seem to be a direct threat to human health. However,
      concentrations of Hg were very high at some sites, and were higher in leaves
      (highest mean value: 1,440 microg/kg dry wt) than in stems (highest mean value:
      422 microg/kg dry wt). This might be a threat, especially to children and
      fetuses, because Hg in I. aquatica was composed of methylmercury, partly or
      totally, at most sites to 11% or less and at one site from 50 to 100%. At the
      latter site, I. aquatica was not cultivated for the food market. Because other
      food sources, such as fish, may have high concentrations of methylmercury, these
      results indicate a need for monitoring of Hg, especially methylmercury, in
      different foodstuffs in the region.

PMID- 12206435
TI  - Uptake of intact zinc-ethylenediaminetetraacetic acid from soil is dependent on
      plant species and complex concentration.
AB  - Pot experiments were conducted with barley (Hordeum vulgare L.), potato (Solanum
      tuberosum L.), Indian mustard (Brassicajuncea L.), and white lupin (Lupinus albus
      L.) to determine the nature of Zn mobilization, uptake, and root-shoot transport
      from a Zn-contaminated soil in the presence of increasing concentrations of
      ethylenediaminetetraacetic acid (EDTA; 0.0-3.4 mmole/kg soil). Increasing EDTA
      concentrations lead to a greater proportion of soil-solution Zn being detected as
      the ZnEDTA complex. However, a significant increase in the concentration of soil
      solution Zn was only observed after the addition of 3.4 mmole EDTA/ kg soil. At
      this application rate, regardless of the plant species, 97 +/- 9% (+/- SD) of the
      increase in soil-solution Zn could be accounted for by chelation/desorption, and
      89 +/- 9% of total Zn in solution was measured as ZnEDTA. Although the complex
      was detected in the xylem exudate of B. juncea after 0.34 mmole EDTA/kg soil had
      been added, ZnEDTA was only found in the xylem exudate of the other plant species
      following the highest application rate of EDTA. In this case, the accumulation of
      Zn and the concentration of ZnEDTA in the xylem sap of B. juncea were
      significantly greater than those of H. vulgare and S. tuberosum. Measurements of
      plant transpiration following the addition of EDTA indicated that B. juncea
      experienced greater physiological stress in the presence of high concentrations
      of EDTA. It was therefore concluded that two different mechanisms of ZnEDTA
      uptake existed for these plant species. Based on a review of the literature, it
      was hypothesized that uptake of ZnEDTA by B. juncea occurred only after
      physiological damage to its root system, whereas uptake by H. vulgare and S.
      tuberosum was via an apoplastic pathway (passive extracellular transport into the
      xylem).

PMID- 12206436
TI  - Detection of environmental androgens: a novel method based on enzyme-linked
      immunosorbent assay of spiggin, the stickleback (Gasterosteus aculeatus) glue
      protein.
AB  - We report the development and validation of a novel in vivo biomarker test for
      waterborne androgens. During breeding, male sticklebacks (Gasterosteus aculeatus)
      manufacture a glue protein, spiggin, in their kidneys that they use to build
      their nests. Spiggin production is under the control of androgens. Until now,
      however, it has only been possible to quantify its production by measurement of
      the height of kidney epithelial cells. In the present study, we report the
      development of an enzyme-linked immunosorbent assay (ELISA) for spiggin and
      demonstrate its application to the measurement of spiggin in the kidneys of
      female sticklebacks that have been exposed to androgens in water. Results from
      the ELISA procedure revealed a strong correlation with measurement of kidney
      epithelial cell height (r2 = 0.93). However, the ELISA was much quicker and had a
      considerably higher response range (100,000-fold vs fourfold). Clear, graded
      responses in spiggin production were obtained by exposing intact females to
      increasing concentrations of 17a-methyltestosterone and 5alpha
      dihydrotestosterone over three-week test periods. The lowest effective
      concentrations for these two steroids were 100 ng/L and 3 micorg/L, respectively.
      Female sticklebacks that were exposed to pulp mill effluent also produced spiggin
      in their kidneys. Possession of an androgen-regulated protein by the female
      stickleback makes it a unique bioassay organism for detecting androgenic
      contamination in the aquatic environment.

PMID- 12206437
TI  - Development of photosynthetic biofilms affected by dissolved and sorbed copper in
      a eutrophic river.
AB  - Photosynthetic biofilms are capable of immobilizing important concentrations of
      metals, therefore reducing bioavailability to organisms. But also metal pollution
      is believed to produce changes in the microalgal species composition of biofilms.
      We investigated the changes undergone by natural photosynthetic biofilms from the
      River Meuse, The Netherlands, under chronic copper (Cu) exposure. The suspended
      particles in the river water had only a minor effect on reduction of sorption and
      toxicity of Cu to algae. Biofilms accumulated Cu proportionally to the added
      concentration, also at the highest concentration used (9 microM Cu). The
      physiognomy of the biofilms was affected through the growth of the chain-forming
      diatom Melosira varians, changing from long filaments to short tufts, although
      species composition was not affected by the Cu exposure. The Cu decreased
      phosphate uptake and algal biomass measured as chl a, which degraded
      exponentially in time. Photosynthetic activity was always less sensitive than
      algal biomass; the photon yield decreased linearly in time. The protective and
      insulating role of the biofilm, supported by ongoing autotrophic activity, was
      indicated as essential in resisting metal toxicity. We discuss the hypothesis
      that the toxic effects of Cu progress almost independently of the species
      composition, counteracting ongoing growth, and conclude that autotrophic biofilms
      act as vertical heterogeneous units. Effective feedback mechanisms and density
      dependence explain several discrepancies observed earlier.

PMID- 12206438
TI  - Metabonomic assessment of toxicity of 4-fluoroaniline, 3,5-difluoroaniline and 2
      fluoro-4-methylaniline to the earthworm Eisenia veneta (Rosa): identification of
      new endogenous biomarkers.
AB  - High-resolution 1H nuclear magnetic resonance (NMR) spectroscopy can be used to
      produce a biochemical fingerprint of low-molecular-weight metabolites from
      complex biological mixtures such as tissue extracts and biofluids. Changes in
      such fingerprint profiles can be used to characterize the effects of toxic insult
      in in vivo systems. The technique is nonselective and requires little sample
      preparation or derivatization. In the present study, earthworms (Eisenia veneta)
      were exposed to three different model xenobiotics by a standard filter paper
      contact test, and toxicant-induced biochemical changes were then investigated by
      characterizing the changes in endogenous metabolites visible in 600-MHz 1H NMR
      spectra of tissue extracts. The NMR spectral intensities were converted to
      discrete numerical values and tabulated in order to provide data matrices
      suitable for multivariate analysis. Principal component analysis showed that
      changes had occurred in the biochemical profiles relative to the undosed
      controls. The 2-fluoro-4-methylaniline-treated worms showed a decrease in a
      resonance from a compound identified as 2-hexyl-5-ethyl-3-furansulfonate using a
      combination of high-performance liquid chromatography (HPLC)-Fourier transform
      mass spectrometry (IonSpec, Lake Forest, CA, USA) and 1H and 13C NMR
      spectroscopy. An increase in inosine monophosphate was also observed. The 4
      fluoroaniline-treated worms showed a decrease in maltose concentrations, and 3,5
      difluoroaniline exerted the same effect as 2-fluoro-4-methylaniline but to a
      lesser extent. These changes could potentially be used as novel biomarkers of
      xenobiotic toxicity and could be used to determine the mechanism of action of
      other toxic chemicals.

PMID- 12206439
TI  - Evaluation of androstenedione as an androgenic component of river water
      downstream of a pulp and paper mill effluent.
AB  - This study evaluates a recent report indicating that androstenedione (4-androsten
      3, 17-dione) contributes to the androgenicity of water downstream of a pulp and
      paper mill discharge on the Fenholloway River (FL, USA). Extraction and
      concentration of Fenholloway water with C18 solid-phase extraction columns
      followed by reverse-phase high-pressure liquid chromatography resulted in clearly
      defined fractions with in vitro androgenic activity in CV-1 cells that had been
      transiently cotransfected with human androgen receptor and reporter gene
      constructs. However, we were unable to detect androstenedione in the active
      fractions by gas chromatography/mass spectrometry. Mass spectrometry analyses of
      deionized and Fenholloway River water samples that had been spiked with
      androstenedione, then extracted and fractionated, revealed that the androgen was
      found only in inactive fractions. We conclude that, although androstenedione was
      present at easily detectable concentrations in the river water (> 100 ng/L), this
      compound is not associated with androgenic activity of water from the site.

PMID- 12206440
TI  - Effects analysis of time-varying or repeated exposures in aquatic ecological risk
      assessment of agrochemicals.
AB  - Exposure to agrochemicals in the aquatic environment often occurs as time-varying
      or repeated pulses. Time-varying exposures may occur due to runoff events and
      spray drift associated with precipitation and application events. Hydrologic
      dilution, dispersion, and degradation also produce pulsed exposures. Standard
      laboratory toxicity tests using constant exposure concentrations typically do not
      investigate the toxicity of time-varying or repeated exposures. Detoxification,
      elimination, and recovery may occur within organisms or populations during the
      periods between exposures. The difficulty of estimating effects of realistic time
      varying exposures from measurements made under constant exposure conditions is
      often an important source of uncertainty in ecological risk assessment of
      pesticides. This article discusses the criteria and tools for deciding whether
      time-varying exposures are relevant in a particular risk assessment, approaches
      for laboratory toxicity testing with time-varying exposure, modeling approaches
      for addressing effects oftime-varying exposure, deterministic and probabilistic
      ecological risk characterization of time-varyingexposures and toxicity, and
      uncertainty analysis.

PMID- 12206441
TI  - Predicting amphipod toxicity from sediment chemistry using logistic regression
      models.
AB  - Individual chemical logistic regression models were developed for 37 chemicals of
      potential concern in contaminated sediments to predict the probability of
      toxicity, based on the standard 10-d survival test for the marine amphipods
      Ampelisca abdita and Rhepoxynius abronius. These models were derived from a large
      database of matching sediment chemistry and toxicity data, which includes
      contaminant gradients from a variety of habitats in coastal North America.
      Chemical concentrations corresponding to a 20, 50, and 80% probability of
      observing sediment toxicity (T20, T50, and T80 values) were calculated to
      illustrate the potential for deriving application-specific sediment effect
      concentrations and to provide probability ranges for evaluating the reliability
      of the models. The individual chemical regression models were combined into a
      single model, using either the maximum (P(Max) model) or average (P(Avg) model)
      probability predicted from the chemicals analyzed in a sample, to estimate the
      probability of toxicity for a sample. The average predicted probability of
      toxicity (from the P(Max) model) within probability quartiles closely matched the
      incidence of toxicity within the same ranges, demonstrating the overall
      reliability of the P(Max) model for the database that was used to derive the
      model. The magnitude of the toxic effect (decreased survival) in the amphipod
      test increased as the predicted probability of toxicity increased. Users have a
      number of options for applying the logistic models, including estimating the
      probability of observing acute toxicity to estuarine and marine amphipods in 10-d
      toxicity tests at any given chemical concentration or estimating the chemical
      concentrations that correspond to specific probabilities of observing sediment
      toxicity.

PMID- 12206442
TI  - Impact of activity behaviors on physical activity identity and self-efficacy.
AB  - OBJECTIVE: To examine the relationship of level of physical activity and length
      of time of adherence to physical activity, with physical activity identity (PAI)
      and physical activity self-efficacy (PASE). METHODS: In a cross-sectional design,
      409 adults completed a survey assessing activity level and adherence, PAI and
      PASE. RESULTS: Vigorous activity was associated with higher scores on PAI and
      PASE scales with activity level contributing significantly larger proportions of
      the variance in scores compared to adherence. CONCLUSION: Effort should be
      invested in encouraging people when beginning an exercise regimen to set a long
      term goal of vigorous activity. This approach may lead to stronger identification
      with and self-efficacy for physical activity leading to greater adherence.

PMID- 12206443
TI  - Stage of motivational readiness: predictive ability for exercise behavior.
AB  - OBJECTIVE: To determine if stage of motivational readiness for exercise predicted
      adherence to a 9-month exercise intervention. METHODS: Three hundred forty-two
      individuals were randomized into a diet and physical activity trial. The exercise
      goal was to complete or add at least 10 miles of weekly brisk walking or jogging.
      Adherence was determined from logs. RESULTS: Sixty-four percent of men and 34% of
      women reported an increase of at least 10 miles per week. Adherence did not
      differ by baseline exercise motivational readiness stage. CONCLUSIONS: Future
      work should determine in what contexts stage-targeted interventions are most
      successful for adoption and maintenance of physical activity.

PMID- 12206444
TI  - Preservice teachers' perceived confidence in teaching school violence prevention.
AB  - OBJECTIVE: To examine preservice teachers' perceived confidence in teaching
      violence prevention and the potential effect of violence-prevention training on
      preservice teachers' confidence in teaching violence prevention. METHODS: Six
      Ohio universities participated in the study. More than 800 undergraduate and
      graduate students completed surveys. RESULTS: Violence-prevention training, area
      of certification, and location of student- teaching placement significantly
      influenced preservice teachers' perceived confidence in teaching violence
      prevention. CONCLUSION: Violence-prevention training positively influences
      preservice teachers' confidence in teaching violence prevention. The results
      suggest that such training should be considered as a requirement for teacher
      preparation programs.

PMID- 12206446
TI  - An evaluation of an abstinence education curriculum series: sex can wait.
AB  - OBJECTIVE: To examine the effects of an abstinence education curriculum series on
      student outcomes. METHODS: The series was taught at upper elementary, junior
      high, and high school levels. A questionnaire was administered to all
      intervention and comparison students before and after implementation of the
      curriculum. RESULTS: At the upper elementary level, the curriculum group had
      better outcomes on knowledge, self-efficacy, and a more hopeful outlook; at the
      middle school level no differences; at the high school level, findings favored
      the curriculum group on attitude, behavioral intent, and sexual behavior
      variables. CONCLUSION: Results are encouraging and should be considered by those
      interested in helping young people postpone sexual involvement.

PMID- 12206445
TI  - Project towards no drug abuse: a review of the findings and future directions.
AB  - OBJECTIVE: To provide a review of the evidence from 3 experimental trials of
      Project Towards No Drug Abuse (TND), a senior-high-school-based drug abuse
      prevention program. METHODS: Theoretical concepts, subjects, designs, hypotheses,
      findings, and conclusions of these trials are presented. A total of 2,468 high
      school youth from 42 schools in southern California were surveyed. RESULTS: The
      Project TND curriculum shows reductions in the use of cigarettes, alcohol,
      marijuana, hard drugs, weapon carrying, and victimization. Most of these results
      were replicated across the 3 trials. CONCLUSION: Project TND is an effective drug
      and violence prevention program for older teens, at least for one-year follow-up.

PMID- 12206447
TI  - Feasibility of a tailored intervention targeting STD-related behaviors.
AB  - OBJECTIVES: To determine if populations at high risk are receptive to tailored,
      multimedia interventions as a means of promoting adoption of health-protective
      behaviors related to STD prevention and control. METHODS: Study participants (N =
      41) were exposed to the tailored, multimedia intervention and asked for feedback.
      RESULTS: Participants were able to interact independently with the intervention.
      A majority found it engaging and indicated that their interaction with the
      intervention would change their future behavior. CONCLUSION: An urban, primarily
      African American sample of STD clinic patients was receptive to this tailored,
      multimedia intervention.

PMID- 12206448
TI  - A comparison of sustained-release bupropion and placebo for smokeless tobacco
      cessation.
AB  - OBJECTIVE: To evaluate the potential efficacy of bupropion sustained release when
      used in combination with minimal counseling for moist snuff cessation in males.
      METHODS: A double-blind, placebo-controlled 3-month trial. The active treatment
      group (n = 35) received bupropion SR at 150 mg/qd day for the first 3 days, then
      beginning day 4 through day 49 (7 weeks) 150 mg/ b.i.d. The placebo group (n= 35)
      received 1 tablet qd for 3 days and beginning day 4 through day 49, 1
      tablet/b.i.d. RESULTS: Bupropion 300 mg/day (150 b.i.d.) produced significantly
      higher quit rates for smokeless tobacco cessation at the end of treatment (7
      weeks) than placebo (p = 0.04) with an OR of 2.73. CONCLUSION: Bupropion SR
      appears to be effective for smokeless tobacco cessation.

PMID- 12206449
TI  - Creating a virtual community using electronic discussion lists.

PMID- 12206450
TI  - Viral strategies of translation initiation: ribosomal shunt and reinitiation.
AB  - Due to the compactness of their genomes, viruses are well suited to the study of
      basic expression mechanisms, including details of transcription, RNA processing,
      transport, and translation. In fact, most basic principles of these processes
      were first described in viral systems. Furthermore, viruses seem not to respect
      basic rules, and cases of "abnormal" expression strategies are quiet common,
      although such strategies are usually also finally observed in rare cases of
      cellular gene expression. Concerning translation, viruses most often violate
      Kozak's original rule that eukaryotic translation starts from a capped
      monocistronic mRNA and involves linear scanning to find the first suitable start
      codon. Thus, many viral cases have been described where translation is initiated
      from noncapped RNA, using an internal ribosome entry site. This review centers on
      other viral translation strategies, namely shunting and virus-controlled
      reinitiation as first described in plant pararetroviruses (Caulimoviridae). In
      shunting, major parts of a complex leader are bypassed and not melted by scanning
      ribosomes. In the Caulimoviridae, this process is coupled to reinitiation after
      translation of a small open reading frame; in other cases, it is possibly
      initiated upon pausing of the scanning ribosome. Most of the Caulimoviridae
      produce polycistronic mRNAs. Two basic mechanisms are used for their translation.
      Alternative translation of the downstream open reading frames in the bacilliform
      Caulimoviridae occurs by a leaky scanning mechanism, and reinitiation of
      polycistronic translation in many of the icosahedral Caulimoviridae is enabled by
      the action of a viral transactivator. Both of these processes are discussed here
      in detail and compared to related processes in other viruses and cells.

PMID- 12206451
TI  - Regulation of pathways of mRNA destabilization and stabilization.
AB  - The level of an mRNA in the cytoplasm represents a balance between the rate at
      which the mRNA precursor is synthesized in the nucleus and the rates of nuclear
      RNA processing and export and cytoplasmic mRNA degradation. Although most studies
      of gene expression have focused on gene transcription and in the area of
      eukaryotic mRNA degradation, but to provide a short general discussion of the
      importance of mRNA degradation and its regulation and a brief overview of recent
      findings and present knowledge. The overview is followed by a more in-depth
      discussion of one of the several pathways for mRNA degradation. We concentrate on
      the pathway for regulated mRNA degradation mediated by mRNA-binding proteins and
      endonucleases that cleave within the body of mRNAs. As a potential example of
      this type of control, we focus on the regulated degradation of the egg yolk
      precursor protein vitellogenin on the mRNA-binding protein vigilin and the mRNA
      endonuclease polysomal ribonuclease 1 (PMR-1).

PMID- 12206452
TI  - Jasmonates and octadecanoids: signals in plant stress responses and development.
AB  - Plants are sessile organisms. Consequently they have to adapt constantly to
      fluctuations in the environment. Some of these changes involve essential factors
      such as nutrients, light, and water. Plants have evolved independent systems to
      sense nutrients such as phosphate and nitrogen. However, many of the
      environmental factors may reach levels which represent stress for the plant. The
      fluctuations can range between moderate and unfavorable, and the factors can be
      of biotic or abiotic origin. Among the biotic factors influencing plant life are
      pathogens and herbivores. In case of bacteria and fungi, symbiotic interactions
      such as nitrogen-fixating nodules and mycorrhiza, respectively, may be
      established. In case of insects, a tritrophic interaction of herbivores,
      carnivores, and plants may occur mutualistically or parasitically. Among the
      numerous abiotic factors are low temperature, frost, heat, high light conditions,
      ultraviolet light, darkness, oxidation stress, hypoxia, wind, touch, nutrient
      imbalance, salt stress, osmotic adjustment, water deficit, and desiccation. In
      the last decade jasmonates were recognized as being signals in plant responses to
      most of these biotic and abiotic factors. Signaling via jasmonates was found to
      occur intracellularly, intercellularly, and systemically as well as
      interorganismically. Jasmonates are a group of ubiquitously occurring plant
      growth regulators originally found as the major constituents in the etheric oil
      of jasmine, and were first suggested to play a role in senescence due to a strong
      senescence-promoting effect. Subsequently, numerous developmental processes were
      described in which jasmonates exhibited hormone-like properties. Recent knowledge
      is reviewed here on jasmonates and their precursors, the octadecanoids. After
      discussing occurrence and biosynthesis, emphasis is placed upon the signal
      transduction pathways in plant stress responses in which jasmonates act as a
      signal. Finally, examples are described on the role of jasmonates in
      developmental processes.

PMID- 12206453
TI  - The ubiquitous nature of RNA chaperone proteins.
AB  - RNA chaperones are ubiquitous and abundant proteins found in all living organisms
      and viruses, where they interact with various classes of RNA. These highly
      diverse families of nucleic acid-binding proteins possess activities enabling
      rapid and faithful RNA-RNA annealing, strand transfer, and exchange and RNA
      ribozyme-mediated cleavage under physiological conditions. RNA chaperones appear
      to be critical to functions as important as maintenance of chromosome ends, DNA
      transcription, preRNA export, splicing and modifications, and mRNA translation
      and degradation. Here we review some of the properties of RNA chaperones in RNA
      RNA interactions that take place during cellular processes and retrovirus
      replication. Examples of cellular and viral proteins are dicussed vis a vis the
      relationships between RNA chaperone activities in vitro and functions. In this
      new "genomic era" we discuss the possible use of small RNA chaperones to improve
      the synthesis of cDNA libraries for use in large screening reactions using DNA
      chips.

PMID- 12206454
TI  - Mechanisms of basal and kinase-inducible transcription activation by CREB.
AB  - The cAMP response element (CRE)-binding protein (CREB) stimulates basal
      transcription of CRE-containing genes and mediates induction of transcription
      upon phosphorylation by protein kinases. The basal activity of CREB maps to a
      carboxy-terminal constitutive activation domain (CAD), whereas phosphorylation
      and inducibility map to a central, kinase-inducible domain (KID). The CAD
      interacts with and recruits the promoter recognition factor TFIID through an
      interaction with a specific TATA-binding-protein-associated factor (TAF),
      dTAFII110/ hTAFII135. Interaction between the TAF and the CAD is mediated by a
      central cluster of hydrophobic amino acids, mutation of which disrupts TAF
      binding, polymerase recruitment, and transcription activation. Assessment of the
      contributions of the CAD and KID to recruitment of the polymerase complex versus
      enhancement of subsequent reaction steps (isomerization, promoter clearance, and
      reinitiation) showed that the CAD and P-KID act in a concerted mechanism to
      stimulate transcription. The CAD, but not the KID, mediated recruitment of a
      complex containing components of a transcription initiation complex, including
      pol II, IIB, and IID. However, the CAD was relatively ineffective in stimulating
      subsequent steps in the reaction mechanism. In contrast, phosphorylation of the
      KID in CREB effectively stimulated isomerization of the recruited polymerase
      complex and multiple-round transcription. A model for the activation of
      transcription by phosphorylated CREB is proposed, in which the polymerase is
      recruited by interaction of the CAD with TFIID and the recruited polymerase is
      activated further by phosphorylation of the KID in CREB.

PMID- 12206455
TI  - eIF4A: the godfather of the DEAD box helicases.
AB  - eIF4A has long been considered the "gold standard" for DEAD box helicases. In
      large measure, this reflected two items: first, the role of eIF4A in protein
      synthesis initiation was relatively well established. Second, a wide variety of
      biochemical studies had established the ability of eIF4A to bind nucleic acids in
      an ATP-dependent manner, to hydrolyze ATP in an RNA-dependent manner, and to
      unwind RNA duplexes in an ATP-dependent manner. In this article, these basic
      observations are reviewed for biochemical consistency and also interpreted in
      light of the available crystal structures for DEAD box proteins. The role of non
      processive vs. processive helicase activity in protein synthesis is discussed.
      Also examined is the influence of ancillary protein factors (eIF4B, eIF4G, and
      eIF4H) on this activity. Finally, the "real" role(s) for eIF4A helicase activity
      in protein synthesis is discussed and related to other circumstances that likely
      also involve the use of non-processive or slightly processive DEAD box helicases
      (ribosome biosynthesis, RNA splicing).

PMID- 12206456
TI  - CTD phosphatase: role in RNA polymerase II cycling and the regulation of
      transcript elongation.
AB  - The repetitive C-terminal domain (CTD) of the largest RNA polymerase II subunit
      plays a critical role in the regulation of gene expression. The activity of the
      CTD is dependent on its state of phosphorylation. A variety of CTD kinases act on
      RNA polymerase II at specific steps in the transcription cycle and preferentially
      phosphorylate distinct positions within the CTD consensus repeat. A single CTD
      phosphatase has been identified and characterized that in concert with CTD
      kinases establishes the level of CTD phosphorylation. The involvement of CTD
      phosphatase in controlling the progression of RNAP II around the transcription
      cycle, the mobilization of stored RNAP IIO, and the regulation of transcript
      elongation and RNA processing is discussed.

PMID- 12206458
TI  - Initiation of eukaryotic DNA replication: regulation and mechanisms.
AB  - The accurate and timely duplication of the genome is a major task for eukaryotic
      cells. This process requires the cooperation of multiple factors to ensure the
      stability of the genetic information of each cell. Mutations, rearrangements, or
      loss of chromosomes can be detrimental to a single cell as well as to the whole
      organism, causing failures, disease, or death. Because of the size of eukaryotic
      genomes, chromosomal duplication is accomplished in a multiparallel process. In
      human somatic cells between 10,000 and 100,000 parallel synthesis sites are
      present. This raises fundamental problems for eukaryotic cells to coordinate the
      start of DNA replication at each origin and to prevent replication of already
      duplicated DNA regions. Since these general phenomena were recognized in the
      middle of the 20th century the regulation and mechanisms of the initiation of
      eukaryotic DNA replication have been intensively investigated. These studies were
      carried out to find the essential factors involved in the process and to
      determine their functions during DNA replication. These studies gave rise to a
      model of the organization and the coordination of DNA replication within the
      eukaryotic cell. The elegant experiments carried out by Rao and Johnson (1970)
      (1), who fused cells in different phases of the cell cycle, showed that G1 cells
      are competent for replication of their chromosomes, but lack a specific
      diffusible factor required to activate their replicaton machinery and showed that
      G2 cells are incompetent for DNA replication. These findings suggested that
      eukaryotic cells exist in two states. In G1 phase, cells are competent to
      initiate DNA replication, which is subsequently triggered in S phase. After
      completion of S phase, cells in G2 are no longer able to initiate DNA replication
      and they require a transition through mitosis to reenable initiation of DNA
      replication to take place in the next S phase. The Xenopus cell-free replication
      system has proved a good model system in which to study DNA replication in vitro
      as well as the mechanism preventing rereplication within a single cell cycle (2).
      Studies using this system resulted in the development of a model postulating the
      existence of a replication licensing factor, which binds to chromatin before the
      G1-S transition and which is displaced during replication (2, 3). These results
      were supported by genetic and biochemical experiments in Saccharomyces cerevisiae
      (budding yeast) and Schizosaccharomyces pombe (fission yeast) (4, 5). The
      investigation of cell division cycle mutants and the budding yeast origin of
      replication resulted in the concept of a prereplicative and a postreplicative
      complex of initiation proteins (6-9). These three individual concepts have
      recently started to merge and it has become obvious that initiation in eukaryotes
      is generally governed by the same ubiquitous mechanisms.

PMID- 12206457
TI  - Translational control of gene expression: role of IRESs and consequences for cell
      transformation and angiogenesis.
AB  - Translational control of gene expression has, over the last 10 years, become
      appreciated as an important process in its regulation in eukaryotes. Among a
      series of control mechanisms exerted at the translational level, the use of
      alternative codons provides a very subtle means of increasing gene diversity by
      expressing several proteins from a single mRNA. The internal ribosome entry sites
      (IRESs) act as specific translational enhancers that allow translation initiation
      to occur independently of the classic cap-dependent mechanism, in response to
      specific stimuli and under the control of different trans-acting factors. It is
      striking to observe that the two processes mostly concern genes coding for
      control proteins such as growth factors, protooncogenes, angiogenesis factors,
      and apoptosis regulators. Here, we focus on the translational regulation of four
      mRNAs, with both IRESs and alternative initiation codons, which are the
      messengers of retroviral murine leukemia virus, fibroblast growth factor 2,
      vascular endothelial growth factor, and protooncogene c-myc. Four of them are
      involved in cell transformation and/or angiogenesis, with important consequences
      for such translation regulations in these pathophysiological processes.

PMID- 12206459
TI  - Structure and function of phi29 hexameric RNA that drives the viral DNA packaging
      motor: review.
AB  - One notable feature of linear dsDNA viruses is that, during replication, their
      lengthy genome is squeezed with remarkable velocity into a preformed procapsid
      and packed into near crystalline density. A molecular motor using ATP as energy
      accomplishes this energetically unfavorable motion tack. In bacterial virus
      phi29, an RNA (pRNA) molecule is a vital component of this motor. This 120-base
      RNA has many novel and distinctive features. It contains strong secondary
      structure, is tightly folded, and unusually stable. Upon interaction with ion and
      proteins, it has a knack to adapt numerous conformations to perform versatile
      function. It can be easily manipulated to form stable homologous monomers,
      dimers, trimers and hexamers. As a result, many unknown properties of RNA have
      been and will be unfolded by the study of this extraordinary molecule. This
      article reviews the structure and function of this pRNA and focuses on novel
      methods and unique approaches that lead to the illumination of its structure and
      function.

PMID- 12206460
TI  - Deoxyribonucleotide synthesis in anaerobic microorganisms: the class III
      ribonucleotide reductase.
AB  - For growth under oxygen-free atmosphere, some strict or facultative anaerobes
      depend on a class III ribonucleotide reductase for the synthesis of
      deoxyribonucleotides, the DNA precursors. Prototypes for this class of enzymes
      are ribonucleotide reductases from Escherichia coli and bacteriophage T4. This
      review article describes their structural and mechanistic properties as well as
      their complex allosteric regulation. Their evolutionnary relationship to class I
      and class II ribonucleotide reductases is also discussed.

PMID- 12206462
TI  - Hispanics and the politics of health care.
AB  - Difficulties with health care for Hispanics are many and complex and have
      consequences. These difficulties are aggravated by their inability to access
      health care. Other issues partner the major problem. They are language barriers,
      culturally insensitive service, no medical coverage and scarce minority health
      professionals and minority researchers to provide critical data. Self-imposed
      isolation and suspicion by the Hispanic community add to the difficulties in
      accessing care. Discussion is followed by recommendations.

PMID- 12206461
TI  - Children of working poor families in California: the effects of insurance status
      on access and utilization of primary health care.
AB  - We examined the effects of health insurance on access and utilization of health
      care among children of working poor families. These children experience strong
      access barriers yet have not been studied systematically. 1,492 children in
      California under 19 years old who had workforce participating parents and a
      subset of full-time year round working families earning below 200% of poverty
      were examined from the 1994 National Health Interview Survey. Thirty-two percent
      of children of working poor families were uninsured in California compared with
      26% nationwide. Difficulties in accessing a regular care source and obtaining
      after-hour care were markedly higher in California. Full-time year round work did
      not increase insurance coverage and worsened access to a regular source of care.
      Uninsured children in California were far more likely than insured children to
      face access barriers and less likely to see a physician in the previous year.
      Between privately and publicly insured children, the gap in access and
      utilization narrowed markedly. Health insurance is critical for children in
      working poor families. Healthy Families, California's response to CHIP, could
      improve coverage for this population.

PMID- 12206463
TI  - Understanding and treating the ethnically Asian client: a collectivist approach.
AB  - Asian clients represent a growing population of clients seeking professional
      assistance for a variety of social and emotional difficulties. Ethnically Asian
      clients often have a collective notion of "self" which is highly influenced by
      family and culture. Clinical work with Asian clients requires very different
      treatment strategies than those used in work with western clients whose notion of
      "self" is far more individualistic. The cultural issues at play in the
      development of a "Collective Self" are described in the article along with common
      crisis situations which often require the Asian client to seek treatment.

PMID- 12206464
TI  - Leadership/citizen participation: perceived impact of advocacy activities by
      people with physical disabilities on access to health care, attendant care and
      social services.
AB  - Increasingly, the climate of shrinking health care resources will impact access
      to health care for the people most vulnerable-those with disabilities. This study
      looked at the perceived impact of leadership and participation by people with
      physical disabilities and at their ability to gain increased access to health
      care, attendant care and social services. Respondents were randomly selected from
      Canada and the United States, from a pool of participants with physical
      disabilities serving in leadership roles within disability organizations in
      either country. Responses from a mail-out survey questionnaire were tabulated
      using logistic regression procedures to identify the perceived impact of advocacy
      activity on improved access to health care, attendant care and social ser- vices.
      Findings suggest that those who participated in advocacy activities were
      significantly more likely to feel that their action improved access to health
      care resources, attendant care resources and social services. Advocates also
      perceived the impact of access for their family, local organizations, and at a
      regional/national level. This study highlights the value of consumer/citizen
      participation, and the vital role this action can play in collaboration with
      social work professionals for system changes, health resource planning and policy
      development.

PMID- 12206465
TI  - The molecular basis of sperm-oocyte membrane interactions during mammalian
      fertilization.
AB  - Gamete membrane interactions begin with adhesion (binding) of the sperm to the
      oocyte plasma membrane and culminate with fusion of the membranes of the gametes,
      thus creating the zygote through the union of these two very different cells.
      This review summarizes the molecular and cell biology of the cell-cell
      interactions between mammalian gametes. Recent research studies have provided new
      insights into the complexity of these interactions and into the importance of
      multimeric molecular networks and optimal membrane order in both sperm and
      oocytes for successful fertilization. Molecules that will be highlighted include
      cysteine-rich secretory protein 1 (CRISP1) and ADAMs [fertilin alpha (ADAM1),
      fertilin beta (ADAM2) and cyritestin (ADAM3)] on sperm, and integrins, CD9, and
      other integrin-associated proteins on oocytes, as well as other molecules. The
      characteristics of these gamete molecules are summarized, followed by discussions
      of the experimental data that provide evidence for their participation in gamete
      membrane interactions, and also of the specific roles that these molecules might
      play. Insights from a variety of research areas, including gamete biology, cell
      adhesion, and membrane fusion, are put together for a tentative model of how
      sperm-oocyte adhesion and fusion occur. The clinical relevance of correct gamete
      membrane interactions is also noted.

PMID- 12206466
TI  - Signalling mechanisms of mammalian oocyte activation.
AB  - Intensive study over the past 10 years has resulted in major advances in our
      understanding of the signalling mechanisms required for the transformation of the
      oocyte into an embryo capable of developing into a new individual. This review
      focuses on the signal transduction events that occur subsequent to the initial
      sperm-oocyte plasma membrane interaction, with particular emphasis on the
      mechanism(s) by which sperm initiate these signalling pathways. Downstream
      signalling/effector molecules that respond to sperm-induced calcium oscillations
      and appear to have important roles in oocyte activation are then discussed.
      Finally, the mechanisms of physiological oocyte activation are compared with
      events of oocyte activation that occur after ICSI.

PMID- 12206467
TI  - The molecular foundations of the maternal to zygotic transition in the
      preimplantation embryo.
AB  - The maternal to zygotic transition is the first major transition that occurs
      following fertilization, and entails a dramatic reprogramming of gene expression
      that is essential for continued development. Although the major reprogramming of
      gene expression occurs during the 2-cell stage, transcription is evident in the 1
      cell embryo, with the male pronucleus supporting a significantly higher level of
      transcription than the female pronucleus. This difference is likely due to
      differences in chromatin structure as a consequence of the protamine-histone
      exchange. Although the 1-cell embryo is transcriptionally competent,
      transcription and translation appear uncoupled. This transcription, however, may
      mark promoters for efficient utilization in the 2-cell embryo. Genome activation
      in the 2-cell embryo is accompanied by a requirement for an enhancer for
      efficient transcription and the more efficient utilization of TATA-less
      promoters. These changes in promoter utilization could contribute substantially
      to the reprogramming of gene expression. Superimposed on genome activation is the
      development of a chromatin-mediated transcriptionally repressive state that is
      relieved by either inducing histone hyperacetylation or inhibiting the second
      round of DNA replication. Since genome activation appears to be a relatively
      opportunistic process, the development of the transcriptionally repressive state
      may be a major determinant in establishing the appropriate gene expression
      profile that is essential for continued development.

PMID- 12206468
TI  - Conception to ongoing pregnancy: the 'black box' of early pregnancy loss.
AB  - Even when conditions are optimal, the maximum chance of a clinically recognized
      pregnancy occurring in a given menstrual cycle is 30-40%. Increasing evidence
      points to preclinical pregnancy loss rather than failure of conception as the
      principal cause for the relatively low fecundity observed in humans. While
      sensitive assays for hCG have provided a glimpse of the events occurring between
      implantation and the missed menstrual period, new cytogenetic techniques have
      further opened this 'black box', providing novel insights into the causes of
      early pregnancy wastage. In this article, the evidence and causes of preclinical
      or 'occult' pregnancy are reviewed, and the implications for the infertile
      patient are addressed.

PMID- 12206469
TI  - Residual ovarian activity during oral steroid contraception.
AB  - Steroid drugs with contraceptive properties have been available in the clinical
      setting for over four decades and are still subject to improvement. Estrogens,
      progestins and anti-progestins have been used alone or in various combinations,
      regimens and routes of administration to favour the balance between efficacy and
      undesirable effects. One of the most important changes in this respect is the
      gradual lowering of steroid dosage in commercially available contraceptives.
      Current steroid contraceptive pills still achieve the goal of suppression of
      pituitary-ovarian activity, but the margins for error are minimal. In this review
      the available data on modes of action and the effects on suppressing pituitary
      ovarian activity by different forms of oral contraception are reassessed.
      Although pregnancy rates provide a crude measure of contraceptive efficacy, no
      benchmark for pituitary-ovarian inhibition is available to test the suppressive
      potential of contraceptive drugs. Consequently, many studies provide incomplete
      and/or incomparable results. For the further study of those forms of steroid
      contraception that rely predominantly on suppression of ovarian activity,
      prevention of dominant follicles selection should be the objective.

PMID- 12206470
TI  - Hormonal contraception: what is new?
AB  - Hormonal contraception has become more effective and more widely used, while the
      world population has grown from 3000 million in 1960 to 6000 million in 2000.
      There is a need for improved contraception, because legal abortion is used in a
      high proportion of pregnancies and illegal abortion continues to be common in
      some countries. Hormonal contraception now includes different choices of
      administration and dose regimens. The best selection depends on the benefits and
      risks of the method and whether there is a medical disability. Medical
      eligibility for combined oral contraceptives has improved during the past 40
      years so that, for most women, all currently available low-dose products are
      safe. For women with medical conditions, wider eligibility for oral contraceptive
      use has evolved from better knowledge of the risk factors. The long-term risks of
      rare cardiovascular and malignant adverse events remain controversial. There are
      long-term benefits, however, as oral contraceptive use appears to protect against
      endometrial, ovarian and colorectal cancers. Emergency contraception provides an
      option that reduces the number of unplanned pregnancies with little or no long
      term risk. Endometrial contraception is an option that would ideally have no
      influence on ovarian function or the bleeding pattern, and cause no significant
      side-effects. Hormonal male contraception, with indirect suppression of
      spermatogenesis by decreasing gonadotrophin output, is a further choice. Although
      hormonal contraception is effective and safe, many research investigations remain
      to be carried out in order to improve tolerance and achieve wider utilization.

PMID- 12206471
TI  - Intrauterine insemination: a systematic review on determinants of success.
AB  - Intrauterine insemination (IUI) is a frequently indicated therapeutic modality in
      infertility. Here, a systematic review of the literature was performed to examine
      the current status of clinical and laboratory methodologies used in IUI and the
      impact of female and male factors on pregnancy success. Emphasis was centred in
      questioning the following: (i) the value of IUI against timed intercourse; (ii)
      IUI application with or without controlled ovarian hyperstimulation; (iii) timing
      and frequency of IUI; and (iv) impact of various parameters (male/female) on the
      prediction of pregnancy outcome. The odds of multiple pregnancy occurrence and
      its risk factors, as well as the cost-effectiveness of IUI treatment compared
      with more complex assisted reproductive technologies are discussed. A
      computerized literature search was performed including Medline and the Cochrane
      library, as well as a crossover search from retrieved papers. It is concluded
      that although IUI is a successful contemporary treatment for appropriately
      selected cases of female and/or male infertility, further research is needed
      through well-designed studies to improve the methodologies currently utilized.
      Importantly, the clinical management of the infertile couple should be performed
      in an expedited manner taking into consideration the age of the woman, the
      presence of multifactorial infertility and cost-effectiveness of the available
      treatment alternatives.

PMID- 12206473
TI  - Newer techniques of radiation therapy in lung cancer.

PMID- 12206472
TI  - A systematic review of the prevalence of Chlamydia trachomatis among European
      women.
AB  - The study aim was to establish by systematic review the prevalence of
      asymptomatic Chlamydia trachomatis infection of the lower female genital tract in
      Europe and also to assess the extent and effect of screening. The search process
      was wide ranging, using the electronic databases Medline, Embase and Aidsline and
      the Internet using the search engines Netscape and Euro-ferret. Studies published
      in any language during 1980-2000 were included if they unambiguously reported
      prevalence of C. trachomatis infection in asymptomatic women, and were assessed
      qualitatively. From >300 papers which quantified C. trachomatis urogenital
      infection, only 14 studies met the inclusion criteria: four from the UK, two from
      Sweden, two from The Netherlands, and one each from Bulgaria, France, Finland,
      Hungary, Italy and Spain. In only one study had screening taken place. The
      prevalence of C. trachomatis in unscreened asymptomatic women in Europe ranges
      from 1.7 to 17% depending upon the setting, context and country. The mode was -6%
      for women seeking contraception, and 4% for women having cervical smears. In
      conclusion, this review confirms high prevalence rates of C. trachomatis
      infection among asymptomatic women in many European settings.

PMID- 12206474
TI  - Clinical profile of tuberculosis in patients with HIV Infection/AIDS.
AB  - Tuberculosis is said to be one of the commonest opportunistic infection in
      patients with HIV/ AIDS. A study was carried out to study the clinical,
      bacteriological and radiological features of HIV/TB patients. Over a period of
      two years, a total of 301 tuberculosis patients were suspected to have HIV/AIDS
      co-infection, and upon testing, 42 patients were found to be HIV seropositive.
      Most of the study patients were manual labourers followed by truck drivers.
      Sexual (heterosexual) route was found to be the major risk factor for HIV/AIDS.
      The most common symptom in these patients was cough and expectoration, followed
      by fever and weight loss. Acid-fast bacilli (AFB) smear positivity was found in
      21.4% patients. On chest skiagram, infiltrative lesions were commonly seen in
      61.9% patients. Extra-pulmonary tubercular manifestations were seen in 45.6% of
      HIV/TB cases.

PMID- 12206475
TI  - An evaluation of salmeterol in the treatment of chronic obstructive pulmonary
      diseases.
AB  - BACKGROUND: Salmeterol has been shown a useful drug for the treatment of chronic
      obstructive pulmonary disease (COPD). However, its positioning in the current
      treatment of COPD remains to be defined. The present study was carried out to
      evaluate its role as an add-on drug to the current first-line drug, ipratropium.
      METHODS: A double-blind randomized, parallel group, placebo-controlled design was
      used in an outpatient setting. Thirty-three patients with moderate or severe COPD
      were included. After a run-in period of two weeks on 40 microg four-times-daily
      ipratropium and 400 microg twice-daily beclomethasone dipropionate, they were
      randomized into two groups to receive either salmeterol (50 microg twice daily)
      or placebo for eight weeks. The outcome parameters were: (i) spirometry, (ii) six
      minute walking test, (iii) SF-36 health-related quality of life (HRQoL)
      questionnaire score, (iv) baseline dyspnoea index (BDI), (v) patient's self
      assessment and (vi) supplemental use of salbutamol. RESULTS: The mean FEV1 and
      FVC increased significantly over the initial values in the salmeterol group but
      not in the placebo group. Salmeterol produced greater improvements in almost all
      the dimensions of HRQoL as well as in the BDI and the supplemental use of
      salbutamol was lower in this group. However, the six-minute walk distance was
      similar in the two groups. CONCLUSIONS: The present study shows that eight weeks
      treatment with salmeterol 50 microg twice-daily added to the existing regimen of
      ipratropium bromide and beclomethasone dipropionate provides greater symptomatic
      relief and improvement in lung function than placebo. This is accompanied by an
      improvement in the health-related quality of life.

PMID- 12206476
TI  - Antibiotic resistance among gram-negative bacteria of lower respiratory tract
      secretions in hospitalized patients.
AB  - Data on antibiotic resistance pattern of gram-negative bacterial isolates of
      lower respiratory tract secretions of hospitalized patients were fed into WHONET
      computer and analyzed for the year 1999. Out of 860 samples, 269 (31.2%) were
      culture positive. Gram-negative bacteria (GNB) accounted for 238 (88.4%) positive
      samples. Non-fermenting gram-negative bacteria (NFGNB) were found in 34% samples,
      the other common ones being Klebsiella spp (29.8%) and Pseudomonas spp (17.2%).
      GNB isolates from tracheal aspirates and sputum were 132 (55.4%) and 106 (44.5%)
      respectively. Adults (32.7%) and elderly patients (24.3%) recorded higher
      isolation of GNB as compared to pediatric patients (1.6%). The highest mean
      resistance among predominant GNB in both tracheal aspirate (96.6%) and sputum
      (86.9%) was noted to ampicillin while the lowest mean resistance in tracheal
      aspirate (28%) and sputum (14.3%) was to amikacin. NFGNB of tracheal aspirates
      and sputum showed highest resistance of 50% and 32% to amikacin, respectively.
      Pseudomonas spp showed the highest variation in the resistance pattern between
      tracheal aspirates and sputum samples. Overall mean resistance was highest among
      tracheal aspirate isolates compared to sputum isolates.

PMID- 12206477
TI  - Screening of early detection of lung cancer.
AB  - Methods for detecting early lung cancers, carcinoma in situ, and dysplastic
      lesions of the tracheobronchial tree ultimately aim to eradicate them before they
      become invasive. This approach is being developed to detect early stage lung
      cancer, when treatment is more likely to be curative. This review describes the
      recent developments in lung cancer screening and the possible impact on
      management of lung cancer.

PMID- 12206478
TI  - Non resolving pneumonia in a young boy.

PMID- 12206479
TI  - Intercostodiaphragmatic hernia secondary to a bull gore injury: a delayed
      detection.
AB  - We report a case of a 45-year-old male presenting with asymptomatic right lower
      chest mass following a forgotten penetrating trauma. This case highlights a rare;
      delayed complication of lower chest penetrating injuries by the bull gore,
      involving the diaphragm. Intercostodiaphragmatic hernia should be kept as a
      differential diagnosis of slowly growing lower chest wall asymptomatic masses
      with forgotten injuries in the past.

PMID- 12206480
TI  - Transdiaphragmatic extension of hepatic hydatid cyst.
AB  - Transdiaphragmatic extension of hydatid cyst (HC) or cystic echinococcosis (CE)
      of the liver is a rare phenomenon. We report a case that presented as a right
      middle lobe consolidation. The diagnosis of transdiaphragmatic extension of
      hepatic hydatid cyst was suspected on CT scan of the chest and abdomen, and
      confirmed operatively. A successful outcome was achieved by a combination of pre-
      and post-operative albendazole therapy combined with surgery.

PMID- 12206481
TI  - Mounier-Kuhn syndrome.
AB  - A variant of Mounier-Kuhn syndrome is reported where the patient had
      bronchiectasis with tracheo-bronchomegaly. The patient also had facial anomalies
      and asthenozoospermia. This combination has not been reported so far in the
      literature.

PMID- 12206482
TI  - Flour mill lung: a pneumoconiosis of mixed aetiology.
AB  - We report two cases of mixed dust fibrosis which occurred in the setting of
      poorly ventilated flour mills where various kinds of grain, chiefly wheat, were
      ground using stones whose silica content was analysed to be greater than 80
      percent. While one patient was a non-smoker and the other was an ex-smoker, both
      cooked on kerosene stoves in the same room. We propose the term 'Flour mill lung'
      for this form of pneumoconiosis. A larger study would be required to establish
      the entity and its incidence among flour mill workers.

PMID- 12206483
TI  - Open lung biopsy in diffuse infiltrative lung disease with progressive dyspnoea:
      is it useful?
AB  - Eleven subjects, aged between 15 and 60 years, presenting with diffuse
      infiltrative lung disease (DILD) and progressive dyspnoea, underwent an open lung
      biopsy (OLB). The authors feel that OLB does give a confidence to the treating
      physician to begin with a specific therapy in the form of steroids. But, as a
      matter of fact, at most health care delivery centres in the country, facilities
      for OLB are not available. Hence, the specific therapy should be instituted
      presumptively following an overall suggestion of disease based upon the clinical,
      physiological (chiefly comprising the pulmonary function test or PFT) and the
      radiological criteria, so that progression of disease could be arrested at an
      early stage.

PMID- 12206484
TI  - Effect of expression of P-glycoprotein on technetium-99m
      methoxyisobutylisonitrile single photon emission computed tomography of brain
      tumors.
AB  - The expression of P-glycoprotein was investigated immunohistochemically in 26
      brain tumor tissues and compared with the findings of technetium-99m
      methoxyisobutylisonitrile single photon emission computed tomography (99mTc-MIBI
      SPECT) to clarify the effect of P-glycoprotein on the diagnostic accuracy. P
      glycoprotein labeling index of both tumor cells and vascular endothelial cells
      showed no clear relationship with the findings of 99mTc-MIBI SPECT imaging.
      Expression of P-glycoprotein has no effect on the diagnostic accuracy of 99mTc
      MIBI SPECT.

PMID- 12206485
TI  - Spontaneous subfalcial transcallosal migration of a missile to the contralateral
      hemisphere causing deterioration in neurological status--case report.
AB  - A 26-year-old man sustained a gunshot injury. Computed tomography (CT)
      demonstrated the missile in the right parietal region. Twenty-four hours later,
      the missile had moved towards the midline. Following slight deterioration in his
      neurological condition one week later, follow-up CT revealed that the missile had
      crossed the midline through the corpus callosum and was located in the left
      parietal region. CT during the second week demonstrated that the missile had
      stopped close to the left parietal bone. Spontaneous migration of a missile to
      the contralateral side via a subfalcial-transcallosal route with deterioration in
      neurological status is unusual. The missile may have moved under the influence of
      the intracranial pressure and pulsatile effect of the cerebrospinal fluid.

PMID- 12206487
TI  - Rapid expansion of benign scalp neurofibroma caused by massive intratumoral
      hemorrhage--case report.
AB  - A 62-year-old man with neurofibromatosis type 1 presented with rapid growth of a
      scalp mass. Head computed tomography demonstrated a large extracranial tumor of
      soft tissue density with massive intratumoral hematoma. Cerebral angiography
      demonstrated remarkable hypervascularity of the tumor. Preoperative embolization
      and total removal of the tumor was performed. The tumor contained a large amount
      of intratumoral hematoma (500 ml). The histological diagnosis was neurofibroma
      without malignant transformation. Benign scalp neurofibroma showing massive
      intratumoral hemorrhage is rare. Rapid growth or intratumoral hemorrhage in
      neurofibroma may be an indicator of malignant transformation.

PMID- 12206486
TI  - Early development and rupture of de novo aneurysm--case report.
AB  - A 38-year-old non-smoker man presented with a ruptured aneurysm one month after
      clipping of a previous aneurysm. He was first admitted because of sudden onset of
      severe headache. Brain computed tomography showed subarachnoid hemorrhage.
      Angiography showed an aneurysm of the left anterior choroidal artery which was
      surgically clipped. Two weeks later, he was discharged without neurological
      deficits. One month after the initial hemorrhage, he was readmitted to the
      emergency room with stuporous mentality. Repeat angiography showed two aneurysms
      of the A2 portion of the left anterior cerebral artery which were not
      demonstrated by the initial angiography. The diagnosis was de novo aneurysms. The
      larger aneurysm was clipped and the other was coated. De novo aneurysm should be
      suspected if a patient with a previously clipped aneurysm complains of typical
      headache or any suggestive symptoms or signs of cranial nerve dysfunction,
      especially if known risk factors are present.

PMID- 12206488
TI  - Magnetic resonance imaging and [11C]methyl-L-methionine positron emission
      tomography of fibrous dysplasia--two case reports.
AB  - Two cases of fibrous dysplasia in the skull base bone appeared hypointense on T1-
      and T2-weighted magnetic resonance imaging, with accumulation of [11C]methyl-L
      methionine ([11C]Met) on positron emission tomography (PET). Fibrous dysplasia is
      a benign bone disorder which is identified by its distinctive radiography,
      computed tomography, and bone scintigraphy findings. [11C]Met PET may indicate
      the presence of viable tumor-like cells in fibrous dysplasia.

PMID- 12206489
TI  - Brain abscess and glioblastoma identified by combined proton magnetic resonance
      spectroscopy and diffusion-weighted magnetic resonance imaging--two case reports.
AB  - The differential diagnosis between brain abscesses and necrotic tumors such as
      glioblastomas is sometimes difficult to establish by conventional computed
      tomography and magnetic resonance imaging. Combined proton magnetic resonance
      spectroscopy (1H-MRS) and diffusion-weighted magnetic resonance imaging (DWI)
      were used to establish the preoperative diagnosis of brain abscess and
      glioblastoma. DWI visualized the brain abscess as a homogeneous hyperintense
      lesion and 1H-MRS revealed the presence of acetate, lactate, and amino acids and
      the absence of the normal brain components. DWI sometimes shows glioblastoma as a
      hyperintense lesion, but 1H-MRS reveals markedly increased lactate and decreased
      N-acetyl-aspartate. Combined DWI and 1H-MRS findings can distinguish brain
      abscess and glioblastoma.

PMID- 12206490
TI  - Intramedullary subependymoma occupying the right half of the thoracic spinal cord
      -case report.
AB  - A 37-year-old female presented with a rare spinal subependymoma manifesting as
      progressive weakness of her right lower extremity over an 8-month period. She had
      a 10-year history of back pain and urinary disturbance. Magnetic resonance
      imaging showed diffuse enlargement of the spinal cord from T-2 to T-7 on the T1
      weighted images. The enlarged spinal cord was divided into two compartments by a
      vertical septum-like structure on the T2-weighted images. The tumor occupied the
      right half of the thoracic spinal cord, and was totally removed through a
      laminectomy from T-2 to T-7. The histological diagnosis of the resected specimen
      was subependymoma. Subependymomas are slow-growing tumors usually found in the
      ventricular system. Spinal subependymomas are difficult to distinguish from other
      intramedullary spinal tumors based on neuroradiological findings. Subependymomas
      are surgically curable tumors, so if the tumor is well demarcated and a
      subependymoma is indicated, an attempt should be made to totally remove the
      tumor.

PMID- 12206491
TI  - Goldenhar's syndrome associated with occipital meningoencephalocele--case report.
AB  - A male neonate presented with Goldenhar's syndrome (oculoauriculovertebral
      dysplasia), a combination of facial microsomia and auricular malformation,
      associated with occipital meningoencephalocele. Three-dimensional computed
      tomography images clearly showed a suboccipital cranial cleft extending to the
      foramen magnum and hypogenesis of the left temporal bone. The patient died of
      heart failure due to ventricular septal defect at age 5 months.

PMID- 12206492
TI  - Visual activation positron emission tomography for presurgical evaluation of
      occipital lobe epilepsy--case report.
AB  - A 14-year-old boy suffered from daily epileptic seizures originating from the
      left polymicrogyric occipital cortex. Visual activation positron emission
      tomography (PET) was used to map the function of the occipital cortex
      presurgically. Loss of visual function in the left occipital cortex was suggested
      by both visual activation PET and electrical cortical stimulation. Left occipital
      lobectomy resulted in a completely seizure-free status without deterioration in
      the visual function. Preoperative evaluation of the visual function in the
      epileptogenic occipital cortex by activation studies using PET or functional
      magnetic resonance imaging is the key to the successful surgical treatment of
      occipital lobe epilepsy.

PMID- 12206493
TI  - Possible acute hemorrhagic leukoencephalitis manifesting as intracerebral
      hemorrhage on computed tomography--case report.
AB  - A 15-year-old girl presented with meningeal irritation and bilateral cerebral
      signs after contracting influenza. A lumbar puncture revealed bloody
      cerebrospinal fluid and polymorphonuclear predominant pleocytosis with an
      elevated protein level and normal glucose level. Computed tomography showed a
      hematoma in the right basal ganglia and lateral ventricles. Symmetrical low
      density areas were also noted in the bilateral white matter. The preliminary
      diagnosis was hemorrhagic cerebrovascular disease of unknown cause. However, her
      neurological condition deteriorated. Magnetic resonance (MR) imaging showed
      diffuse high intensity signals in the bilateral white matter and small spotty
      lesions, indicating hemorrhages in various stages. The final diagnosis was acute
      hemorrhagic leukoencephalitis (AHL). However, high-dose steroid administration
      and plasmapheresis failed to improve her condition. Hypothermia could not control
      her intracranial pressure and she died 12 days after admission. The neuroimaging
      findings indicated the histological characteristics of AHL, but the hematoma
      formation is rare. AHL is a fulminant form of brain demyelination and can be
      fatal, so early diagnosis and aggressive treatment are important for successful
      recovery. Therefore, early investigation by MR imaging is necessary.

PMID- 12206494
TI  - Chiral crystallization of anti-dodecaisopropyltricyclo-[4.2.00.0(2,5)]
      octasilane.
AB  - The aim of this article is to describe the results of our investigation on the
      chiral crystallization of anti-tricyclic ladder polysilane, anti
      dodecaisopropyltricyclo [4.2.0.0(2,5)] octasilane (1). In solid state, the
      silicon framework of 1 adopts twisted conformation in which the Si4 rings are
      puckered in the same direction. Crystallization of 1 afforded a large
      conglomerate crystal in high yield. X-ray crystallography revealed that the
      crystal consists of either right-handed (P) or left-handed (M) molecules. The
      ultraviolet and circular dichroism spectra of the chiral crystals of 1 reveal two
      absorption bands in the 400-250 nm region.

PMID- 12206495
TI  - Vibrational circular dichroism in the near infrared: instrumental developments
      and applications.
AB  - Near infrared vibrational circular dichroism spectra in the region of 1300 to 800
      nm were recorded for 12 enantiomeric pairs of molecules with a home-made
      dispersive apparatus. With respect to earlier measurements, a better signal-to
      noise ratio was obtained, thus allowing a more precise determination of molecular
      parameters. A detailed examination of the spectra between 1300 and 1100 nm
      allowed us to correlate the data of the different molecules, based on local
      properties of given molecular moieties. The relevance of this correlation in
      configurational and/or conformational studies is discussed.

PMID- 12206496
TI  - High-performance photoelastic modulator for polarization modulation spectrometer.
AB  - A high-performance photoelastic modulator (PEM) has been built. It consists of a
      home-made PEM head and a home-built PEM driver that is based on the principle of
      the phase-locked loop (PLL) (PLL PEM driver). It was installed in our new type
      circular dichroism (CD) spectrometer for visible light region and its performance
      was evaluated. With the phase angle being set exactly to zero, the PEM is found
      to be about eight times more efficient than commercially available one. The
      efficiency of PEM depends not only on the efficiency of PEM driver but also on
      the quality of PEM head. The latter can be estimated from admittance-parameter
      measurements without installing it into a spectrometer. With substituting the PLL
      PEM driver for a conventional one, the PEM drive voltage can be reduced from one
      half to one-third and the baseline shift for air blank that is a measure of the
      total performance of polarization modulation spectrometers becomes quite small.

PMID- 12206497
TI  - Circular dichroism of amino acid films in UV-VUV region.
AB  - Circular dichroism (CD) spectra of sublimated films of alanine and alanine
      dipeptide were measured in UV-VUV region. When a film has some linear anisotropy,
      the apparent CD signal is known to be strongly distributed by linear anisotropy.
      In order to obtain the true CD spectra, we examined this disturbance for L
      alanine films. We measured linear dichroism spectra and CD spectra as a function
      of the sample rotation angle, turning the sample over. On the basis of these
      measurements, we concluded that the linear anisotropy contribution to CD was
      sufficiently small for carefully prepared films. In addition, we revealed that it
      is essential for accurate measurement to prepare thin film of which thickness is
      smaller than 100 nm for the case of alanine films. CD of amino acid films was
      compared with that of aqueous solution. Sign of CD signal of solid films was
      observed to be the same for aspartic acid, but it was reversed from that of
      aqueous solution for alanine and alanine dipeptide.

PMID- 12206498
TI  - Vibrational circular dichroism spectrum of 1-amino-2-propanol.
AB  - Vibrational circular dichroism (VCD) spectra of 1-amino-2-propanol, of neat
      sample and in dilute solution of CDCl3, were measured in 2000 to 800 cm(-1)
      region. Two VCD bands, which appear at 1272 and 1412 cm(-1) in dilute solution,
      were assigned, respectively, to the OH bending mode and the mode that is
      influenced by the OH bending of the most stable conformer. The assignments were
      confirmed according to the prediction by a high-level density function theory
      (DFT) calculation and the isotope shift of deuterated samples. The joint analysis
      of the spectra obtained by the VCD and ordinary infrared (IR) measurements seems
      to be a useful way of using vibrational spectroscopy to investigate the hydrogen
      bonding system in solution.

PMID- 12206499
TI  - CD and ACD spectroscopy on anisotropic samples: chirality of oriented molecules
      and anisotropic phases--a critical analysis.
AB  - Chiral anisotropic phases exhibit an elliptical birefringence and dichroism
      instead of the circular effects of isotropic dissymmetric and the linear effects
      of achiral anisotropic phases. Therefore, techniques to determine chiral effects
      of chiral anisotropic phases yield not always results of chirality measurements,
      namely, pseudoscalar quantities. From definitions for a chirality measurement
      with non-oriented and oriented macroscopic anisotropic phases procedures are
      derived by which the pseudoscalar contribution included in the elliptical
      birefringence and dichroism can be obtained. Within this description the CD of
      chiral microcrystallites, isotropically distributed in pressed KBr plates or in
      Nujol, is a chirality measurement. With an excess of anisotropic distributed
      material in pressed KBr plates or, in general, with oriented macroscopic
      anisotropic phases, the ACD is no longer a pseudoscalar. An achiral information
      is included in the ACD which is not an artifact obtained by the mixing of
      "circular and linear effects" via nonideal optical elements in a CD spectrometer.

PMID- 12206500
TI  - Circular dichroism spectra of regioregular poly[3 [(S)-2-methylbutyl]-thiophene]
      and of poly[3,4-di[(S)-2-methylbutyl]-thiophene].
AB  - Ultraviolet absorption and Circular Dichroism spectra in the region 300-700 nm
      for highly regioregular samples of Poly[3[(S)-2-methylbutyl]-thiophene] are
      reported for solutions in good and poor solvents, at variable temperature, and
      for films in various conditions. In the latter case novel CD data up to the
      melting temperature provide some hints for the self-assembling process towards
      supramolecular organization. UV-visible and CD data are also reported on the
      related polymer Poly[3,4-di[(S)-2-methylbutyl]-thiophene].

PMID- 12206501
TI  - Comparison of CD spectra of (2-methylphenyl)- and (2,6-dimethylphenyl)
      phenylmethanols leads to erroneous absolute configurations.
AB  - Enantiopure (2,6-dimethylphenyl)phenylmethanol (+)-(3) and analog (+)-(4) were
      prepared and their CD spectra were found opposite to that of (2
      methylphenyl)phenylmethanol (R)-(-)-(2), the absolute configuration of which was
      previously established by X-ray crystallography. Therefore the S absolute
      configuration was once assigned to (+)-3 and (+)-4. After that we have succeeded
      in the X-ray analyses of chiral dichlorophthalate esters of (+)-3 and (+)4, which
      clearly indicated R absolute configuration. It is thus evident that comparison of
      the CD spectra of alcohols 2, 3, and 4 leads to erroneous absolute
      configurations.

PMID- 12206502
TI  - Crystalline state conformation of 2-methoxy-2-(1-naphthyl)propionic acid ester.
AB  - The enantioresolution method using (S)-(+)-2-methoxy-2-(1-naphthyl)propionic acid
      (MalphaNP acid 1) was applied to 1,2,3,4-tetrahydro-4-phenanthrenol (4). Racemic
      alcohol (+/-)-4 was esterified with (S)-(+)-1, and a diastereomeric mixture of
      esters formed was separated by HPLC on silica gel giving the first-eluted ester
      5a and the second-eluted one 5b. Ester 5a was reduced with LiAlH4 yielding
      enantiopure alcohol (+)-4. A single crystal of ester 5a was subjected to X-ray
      crystallography to determine its absolute configuration as (S,S), and therefore
      to assign the S absolute configuration to (+)-4. The most striking finding in the
      X-ray analysis is that the methoxyl oxygen atom is syn to the ester carbonyl
      oxygen even in the crystalline state. This is just the preferred conformation of
      MalphaNP acid esters assumed in the 1H NMR anisotropy method. The S absolute
      configuration of (+)-4 was also confirmed by the CD and 1H NMR anisotropy
      methods.

PMID- 12206503
TI  - Fluorescence-detected circular dichroism by modulated beam in the wavelength
      axial direction.
AB  - A novel device is described that permits fluorescence-detected circular dichroism
      (FDCD) detection in a conventional fluorescence spectrophotometer. FDCD is a
      phenomenon in which the emission intensity of a chiral analyte depends on the
      polarization state of the excitations. Although FDCD is a sensitive chiral
      detection technique, measurement of FDCD by using a special CD spectrometer has
      involved many difficulties. The proposed device consists of a polarizing prism
      and a retardation plate that fit on the excitation light side in the sample
      compartment of the fluorescence spectrophotometer. In this method, a FDCD wave
      superimposed on the fluorescence excitation spectrum of a chiral analyte was
      detected. We have also demonstrated the possibility of the enantiomeric purity
      determination of chiral analytes in real samples.

PMID- 12206504
TI  - Kinetic resolution of beta- and gamma-hydroxy sulfides by fungal lipase from
      Humicola lanuginosa.
AB  - Racemic beta- and gamma-hydroxy sulfides were resolved by Humicola lanuginosa
      lipase catalyzed transesterification using vinyl acetate both as acyl donor and
      solvent. The effect of substituents and spacer length on rate of reaction and
      enantioselectivity is observed.

PMID- 12206505
TI  - Secondary structural studies of bovine caseins: structure and temperature
      dependence of beta-casein phosphopeptide (1-25) as analyzed by circular
      dichroism, FTIR spectroscopy, and analytical ultracentrifugation.
AB  - The defining structural feature of all of the caseins is their common
      phosphorylation sequence. In milk, these phosphoserine residues combine with
      inorganic calcium and phosphate to form colloidal complexes. In addition,
      nutritional benefits have been ascribed to the phosphopeptides from casein. To
      obtain a molecular basis for the functional, chemical, and biochemical properties
      of these casein peptides, the secondary structure of the phosphopeptide of bovine
      beta-casein (1-25) was reexamined using Fourier transform infrared (FTIR) and
      circular dichroism (CD) spectroscopies. Both methods predict secondary structures
      for the peptide which include polyproline II elements as well as beta-extended
      sheet and turn-like elements. These structural elements were highly stable from 5
      degrees to 70 degrees C. Reexamination of previously published 1H NMR data using
      chemical shift indices suggests structures in accord with the CD and FTIR data.
      Dephosphorylation showed little or no secondary structural changes, as monitored
      by CD and FTIR, but the modified peptide demonstrated pronounced self
      association. The polymers formed were not highly temperature sensitive, but were
      pressure sensitive as judged by analytical ultracentrifugation at selected rotor
      speeds. Molecular dynamics (MD) simulations demonstrated relatively large volume
      changes for the dephosphorylated peptide, in accord with the pressure dependent
      aggregation observed in the analytical ultracentrifuge data. In contrast the
      native peptide in MD remained relatively rigid. The physical properties of the
      peptide suggest how phosphorylation can alter its biochemical and physiological
      properties.

PMID- 12206506
TI  - Effect of chaotropic agents on the structure-function of recombinant acylpeptide
      hydrolase.
AB  - Acylpeptide hydrolase, a new class the serine-type peptidase, belongs to the
      alpha,beta hydrolase group of proteins. The tetrameric enzyme showed varying
      degree of stability in the presence of 1-8 M urea. The enzyme displayed about 15%
      of its original activity when treated with 8 M urea for 1 h at 25 degrees C.
      Complete recovery of the enzyme activity was observed on dialysis or dilution (50
      fold) of the denatured enzyme. However, complete abolition of the enzyme activity
      was observed in the presence of 1 M GnHCl. Dialysis of the 1 M GnHCl-treated
      enzyme resulted in 15-20% recovery of the enzyme activity. The fluorescence
      emission spectra of the native enzyme at 337 nm showed a red shift up to 16 nm in
      8 M urea and 18 nm in the presence of 4 M GnHCl. Native enzyme during far-UV
      circular dichroism spectroscopy exhibited predominantly beta-sheet structure. The
      enzyme lost its secondary structure at urea concentrations of 2 M and higher,
      whereas the tertiary structure was minimally perturbed below 4 M urea. However,
      in 1 M GnHCl the enzyme lost both its secondary and tertiary structures and the
      enzyme was found to dissociate into monomers of 70 kDa. Both monomeric and
      dimeric species were observed after 24-h dialysis of the enzyme denatured with
      GnHCl indicating the reassociation process. Both monomer and dimers forms
      recovered after dialysis were active.

PMID- 12206507
TI  - Substrate size selectivity of 20S proteasomes: analysis with variable-sized
      synthetic substrates.
AB  - Proteasomes are tubular complexes with proteolytic activities on their lumenal
      surfaces so that large substrates should be sterically hindered from reaching the
      catalytic sites. Here we examine effects of substrate size on rates of cleavage
      by 20S proteasomes of Methanosarcina thermophila. Synthetic chromogenic
      substrates of variable size were prepared by linking a constant substrate group
      (Ala-Ala-Phe-p-nitroanilide) to a linear polymer (methoxypolyethylene glycol)
      with variable chain length. The smallest macromolecular substrates were cleaved
      more efficiently than free tripeptide substrate, and cleavage of macromolecular
      substrates was saturable, whereas cleavage of free tripeptide substrate was not,
      indicating mechanistic differences between the cleavage of large and small
      substrates. Rates of macromolecular substrate cleavage decreased progressively up
      to 10-fold as the size of the polymeric component of substrates increased.
      Macromolecular synthetic substrates appear to be better models of proteasome
      action on natural protein substrates and demonstrate substrate size selectivity
      of proteasomes.

PMID- 12206508
TI  - Affinity labeling of the guanine nucleotide binding site of transducin by
      pyridoxal 5'-phosphate.
AB  - Transducin (T), a guanine nucleotide binding regulatory protein composed of alpha
      , beta-, and gamma-subunits, serves as an intermediary between rhodopsin and cGMP
      phosphodiesterase during signaling in the visual process. Pyridoxal 5'-phosphate
      (PLP), a reagent that has been used to modify enzymes that bind phosphorylated
      substrates, was probed here as an affinity label for T. PLP inhibited the guanine
      nucleotide binding activity of T in a concentration dependent manner, and was
      covalently incorporated into the protein in the presence of [3H]NaBH4.
      Approximately 1 mol of 3H was bound per mol of T. GTP and GTP analogs appreciably
      hindered the incorporation of 3H to T, suggesting that PLP specifically modified
      the protein active site. Interestingly, PLP modified both the alpha- and beta
      subunits of T. Moreover, PLP in the presence of GDP behaved as a GTP analog,
      since this mixture was capable of dissociating T from T:photoactivated rhodopsin
      complexes.

PMID- 12206509
TI  - Comparison of the average structures, from molecular dynamics, of complexes of
      GTPase activating protein (GAP) with oncogenic and wild-type ras-p21:
      identification of potential effector domains.
AB  - GTPase activating protein (GAP) is a known regulator of ras-p21 activity and is a
      likely target of ras-induced mitogenic signaling. The domains of GAP that may be
      involved in this signaling are unknown. In order to infer which domains of GAP
      may be involved, we have performed molecular dynamics calculations of GAP
      complexed to wild-type and oncogenic (Val 12-containing) ras-p21, both bound to
      GTP. We have computed and superimposed the average structures for both complexes
      and find that there are four domains of GAP that undergo major changes in
      conformation: residues 821-851, 917-924, 943-953, and 1003-1020. With the
      exception of the 943-953 domain, none of these domains is involved in making
      contacts with ras-p21, and all of them occur on the surface of the protein,
      making them good candidates for effector domains. In addition, three ras-p21
      domains undergo major structural changes in the oncogenic p21-GAP complex: 71-76
      from the switch 2 domain; 100-108, which interacts with SOS, jun and jun kinase
      (JNK); and residues 122-138. The change in conformation of the 71-76 domain
      appears to be induced by changes in conformation in the switch 1 domain (residues
      32-40) and in the adjacent domain involving residues 21-31. In an accompanying
      paper, we present results from microinjection of peptides corresponding to each
      of these domains into oocytes induced to undergo maturation by oncogenic ras-p21
      and by insulin-activated wild-type cellular p21 to determine whether these domain
      peptides may be involved in ras signaling through GAP.

PMID- 12206510
TI  - Inhibition of ras-induced oocyte maturation by peptides from ras-p21 and GTPase
      activating protein (GAP) identified as being effector domains from molecular
      dynamics calculations.
AB  - In the accompanying article, using molecular dynamics calculations, we found that
      the 66-77 and 122-138 domains in ras-p21 and the 821-827, 832-845, 917-924, 943
      953, and 1003-1020 domains in GAP have different conformations in complexes of
      GAP with wild-type and oncogenic ras-p21. We have now synthesized peptides
      corresponding to each of these domains and coinjected them into oocytes with
      oncogenic p21, which induces oocyte maturation, or injected them into oocytes
      incubated with insulin that induces maturation by activating wild-type cellular
      ras-p21. We find that all of these peptides inhibit both agents but do not
      inhibit progesterone-induced maturation that occurs by a ras-independent pathway.
      The p21 66-77 and 122-138 peptides cause greater inhibition of oncogenic p21. On
      the other hand, the GAP 832-845 and 1003-1021 peptides inhibit insulin-induced
      maturation to a significantly greater extent. Since we have found that activated
      wild-type and oncogenic p21 activate downstream targets like raf differently,
      these GAP peptides may be useful probes for identifying elements unique to the
      wild-type ras-p21 pathway.

PMID- 12206511
TI  - Identification of the site of inhibition of mitogenic signaling by oncogenic ras
      p21 by a ras effector peptide.
AB  - We have previously found that a ras switch 1 domain peptide (PNC-7, residues 35
      47) selectively blocks oocyte maturation induced by oncogenic (Val 12-containing)
      ras-p21 protein and also blocks c-raf-induced oocyte maturation. We now find that
      oncogenic ras-p21 does not inhibit oocyte maturation of a constitutively
      activated raf protein (raf BXB) that is lacking most of the first 301 amino
      terminal amino acids, including the major ras binding domain and accessory ras
      binding regions. We also find that a dominant negative raf that completely blocks
      c-raf-induced maturation likewise does not block raf-BXB-induced maturation. We
      conclude that PNC-7 blocks ras by binding to the amino-terminal domain of raf and
      that raf BXB must initiate signal transduction in the cytosol.

PMID- 12206512
TI  - Rates for breast cancer characteristics by estrogen and progesterone receptor
      status in the major racial/ethnic groups.
AB  - It has been reported that age-specific breast cancer rates vary by estrogen
      receptor and progesterone receptor status. We report breast cancer rates for age
      at-diagnosis, stage-at-diagnosis, histological grade and type by estrogen (ER)
      and progesterone (PgR) receptor status in six major racial/ethnic groups. The
      average annual age-adjusted rates for breast cancers with estrogen receptor
      positive (ER+), ER-, progesterone receptor positive (PgR+), PgR-, ER+PgR+, ER+PgR
      , ER-PgR+ and ER-PgR- are determined from 123,732 breast cancers with known ER
      status, diagnosed from 1992 to 1998 from 11 Surveillance, Epidemiology, and End
      Results (SEER) cancer registries. For each racial/ethnic group, their ER+
      (ER+PgR+ and ER+PgR-) age-specific rates increased with age (but at a slower pace
      after ages 50-54) while their ER- (ER- PgR+ and ER-PgR-) age-specific rates did
      not increase after ages 50-54. The rank orders of the rates among the
      racial/ethnic groups varied by ER/PgR status. The stage I rates were greater than
      the stage II rates for the ER/PgR groups except for ER- and ER- PgR- cancers. The
      grade 2 (moderately differentiated) rates were greater than the grades 3 and 4
      (poorly differentiated and undifferentiated cancers) rates for ER+ cancers, but
      not for ER- cancers. These results suggest that although breast cancer is a
      disease with enormous heterogeneity, the multiple types of breast cancer can be
      separated into distinct subgroups by their ER status, and perhaps by their ER/PgR
      status, and their cancer characteristics may be important in understanding the
      multiple nature of breast cancer.

PMID- 12206513
TI  - Prognostic value of thermographical findings in patients with primary breast
      cancer.
AB  - Thermography is a technique to measure the body surface temperature and is used
      in medical applications. We evaluated its prognostic value in 340 female patients
      with unilateral invasive breast cancer without distant metastases. The difference
      of mean temperatures of the tumor area and corresponding area of the
      contralateral breast was defined as AT. The patients with hot tumors (delta T >
      or = 0.9 degrees C) had significantly worse disease free and specific survival
      than those with cold tumors (delta T < 0.9 degrees C) (p = 0.0003 and p < 0.0001,
      respectively). AT was significantly correlated with tumor size, histological
      nodal status and nuclear grade, positively. But AT did not have any relation with
      estrogen receptor status. Multivariate analyses including those conventional
      prognostic factors showed that AT was a marginally significant prognostic factor
      for disease-free survival (hazard ratio (HR) = 1.62; 95% confidence interval (CI)
      = 0.99-2.66, p = 0.0557) and an independent significant prognostic one for
      disease specific survival (HR = 1.95; 95% CI = 1.09-3.49, p = 0.0251). However,
      AT did not have prognostic impact on the node negative patients. AT might be a
      useful prognostic factor in node positive breast cancer, especially in patients
      who plan to be treated with preoperative systemic therapy.

PMID- 12206514
TI  - The Long Island Breast Cancer Study Project: description of a multi-institutional
      collaboration to identify environmental risk factors for breast cancer.
AB  - The Long Island Breast Cancer Study Project is a federally mandated, population
      based case-control study to determine whether breast cancer risk among women in
      the counties of Nassau and Suffolk, NY, is associated with selected environmental
      exposures, assessed by blood samples, self-reports, and environmental home
      samples. This report describes the collaborative project's background, rationale,
      methods, participation rates, and distributions of known risk factors for breast
      cancer by case-control status, by blood donation, and by availability of
      environmental home samples. Interview response rates among eligible cases and
      controls were 82.1% (n = 1,508) and 62.8% (n = 1,556), respectively. Among case
      and control respondents who completed the interviewer-administered questionnaire,
      98.2 and 97.6% self-completed the food frequency questionnaire; 73.0 and 73.3%
      donated a blood sample; and 93.0 and 83.3% donated a urine sample. Among a random
      sample of case and control respondents who are long-term residents, samples of
      dust (83.6 and 83.0%); soil (93.5 and 89.7%); and water (94.3 and 93.9%) were
      collected. Established risk factors for breast cancer that were found to increase
      risk among Long Island women include lower parity, late age at first birth,
      little or no breast feeding, and family history of breast cancer. Factors that
      were found to be associated with a decreased likelihood that a respondent would
      donate blood include increasing age and past smoking; factors associated with an
      increased probability include white or other race, alcohol use, ever breastfed,
      ever use of hormone replacement therapy, ever use of oral contraceptives, and
      ever had a mammogram. Long-term residents (defined as 15+ years in the interview
      home) with environmental home samples did not differ from other long-term
      residents, although there were a number of differences in risk factor
      distributions between long-term residents and other participants, as anticipated.

PMID- 12206515
TI  - Differential gene expression of TGF-beta family members and osteopontin in breast
      tumor tissue: analysis by real-time quantitative PCR.
AB  - Several cytokines including members of the transforming growth factor-beta (TGF
      beta) and tumor necrosis factor (TNF) families have been implicated in the homing
      mechanism of breast cancer metastasis. We hypothesize that primary breast tumor
      tissues differentially express modulators of bone cell function and that this
      expression pattern contributes to their aggressive and metastatic potential and
      to their capacity to establish and grow in bone. We, therefore, examined the gene
      expression pattern of the TGF-beta family members (inhibin/activin betaA subunit
      (activin betaA), inhibin alpha subunit, and bone morphogenetic protein-2 (BMP
      2)), the TNF family members (receptor activator of NF-KB ligand (RANKL) and
      osteoprotegerin (OPG)), and osteopontin (OPN) in normal, non-invasive, invasive,
      and metastatic human breast cancer specimens. The mRNA transcript levels of these
      genes were quantified by reverse transcription (RT) and fluorescent-based kinetic
      PCR in 18 normal breast tissues, five ductal carcinoma in situ (DCIS). 24 primary
      breast tumor tissue, and five distant metastases. The mRNA transcript level of
      each gene was normalized to the amount of beta-actin present in the samples. We
      observed differential gene expression of the selected TGF-beta family members as
      well as OPN in breast cancer progression. The average gene expression of the
      putative tumor suppressor, inhibin alpha, did not significantly change in any of
      the tumor tissues examined compared to normal breast tissue. The mRNA level of
      BMP-2, a protein with anti-proliferative effects in breast cancer cell lines and
      involved in bone formation, significantly decreased in non-invasive, invasive,
      and liver metastatic breast tumor tissue compared to normal breast tissue. The
      gene expression of activin betaA, a protein involved in cell proliferation and
      osteoclast induction, increased in invasive and bone metastatic tumor tissue
      compared to normal breast tissue. The mRNA level of OPN, a bone matrix protein
      associated with enhanced malignancy, increased in non-invasive, invasive, and
      liver and bone metastatic breast tumor tissue compared to normal breast tissue.
      In contrast, the average gene expressions of the TNF family members, RANKL and
      OPG, proteins involved in the regulation of osteoclastogenesis, were only
      slightly if at all changed in the different stage breast tumor tissues. These
      results suggest that differential gene expression of bone-related proteins,
      especially OPN, activin betaA, and BMP-2, by primary breast tumor tissues may
      play a significant role in the invasiveness and metastatic potential of breast
      cancer.

PMID- 12206516
TI  - Association between nitrotyrosine levels and microvascular density in human
      breast cancer.
AB  - Nitrotyrosine (NO2Y) is a global marker of protein modification by reactive
      nitrogen species such as peroxynitrite derived from nitric oxide (NO). Because NO
      and its derivatives are postulated to enhance carcinogenesis, we used stable
      isotope dilution mass spectrometry to measure the levels of NO2Y in 30 samples of
      human breast cancer of varying pathologic types. In the samples tested, the NO2Y
      levels were generally low (average of 14.1 +/- 9.2 micromol NO2Y per mole of
      tyrosine). Breast cancers with a high microvascular density, however, had a
      significantly higher average level of NO2Y than tumors with a low microvascular
      density (20 v.s. 10 micromol NO2Y per mole of tyrosine, p = 0.007 by two-tailed t
      test, assuming unequal variances of two samples). There was no apparent
      association between NO2Y levels and the differentiation of the tumors, tumor
      aneuploidy, estrogen receptor status, HER-2 expression, lymph node status, or
      infiltration of the tumors by neutrophils or eosinophils. When the tissues were
      stained by immunohistochemistry for NO2Y, the NO2Y was localized predominantly
      within inflammatory cells located immediately adjacent to blood vessels at the
      edges of the tumors. NO2Y was generally not evident within the tumor cells or
      inflammatory cells in the stroma. We conclude that low levels of reactive
      nitrogen species are located predominantly within inflammatory cells near blood
      vessels of breast cancer and that higher NO2Y levels are associated with an
      increased density of blood vessels. Our findings, therefore, support a possible
      association between inflammatory cells and reactive nitrogen species in
      modulating microvascular density at the edges of breast cancer.

PMID- 12206517
TI  - Sequencing surgery, radiotherapy and chemotherapy: insights from a mathematical
      analysis.
AB  - We present results from a mathematical analysis that is aimed at finding the best
      way to sequence the three traditional cancer treatments: surgery (S),
      chemotherapy (C), and radiotherapy (R). The mathematical model tracks the
      temporal evolution of the primary tumor and its associated metastases, and
      incorporates the primary tumor's effect on the dormancy and growth of the
      metastases. We show that the SCR schedule (i.e., surgery followed by chemotherapy
      followed by radiotherapy) achieves a higher cure probability than SRC if the
      primary tumor is sufficiently large or if the metastatic population is
      sufficiently large relative to the primary tumor. We also show that a novel
      schedule, SRCR, which splits the radiotherapy regimen into two disjoint portions,
      is optimal among all schedules, provided that the patient's dormant metastatic
      tumors do not become vascularized within about 40 days after surgery.

PMID- 12206518
TI  - An in vitro study of the reduction in wear of metal-on-metal hip prostheses using
      surface-engineered femoral heads.
AB  - Although the wear of existing metal-on-metal (MOM) hip prostheses (1 mm3/10(6)
      cycles) is much lower than the more widely used polyethylene-on-metal bearings,
      there are concerns about the toxicity of metal wear particles and elevated metal
      ion levels, both locally and systemically, in the human body. The aim of this
      study was to investigate the possibility of reducing the volume of wear, the
      concentration of metal debris and the level of metal ion release through using
      surface-engineered femoral heads. Three thick (8-12 microm) coatings (TiN, CrN
      and CrCN) and one thin (2 microm) coating (diamond-like carbon, DLC), were
      evaluated on the femoral heads when articulating against high carbon content
      cobalt-chromium alloy acetabular inserts (HC CoCrMo) and compared with a
      clinically used MOM cobalt-chromium alloy bearing couple using a physiological
      anatomical hip joint simulator (Leeds Mark II). This study showed that CrN, CrCN
      and DLC coatings produced substantially lower wear volumes for both the coated
      femoral heads and the HC CoCrMo inserts. The TiN coating itself had little wear,
      but it caused relatively high wear of the HC CoCrMo inserts compared with the
      other coatings. The majority of the wear debris for all half-coated couples
      comprised small, 30 nm or less, CoCrMo metal particles. The Co, Cr and Mo ion
      concentrations released from the bearing couples of CrN-, CrCN- and DLC-coated
      heads articulating against HC CoCrMo inserts were at least 7 times lower than
      those released from the clinical MOM prostheses. These surface-engineered femoral
      heads articulating on HC CoCrMo acetabular inserts produced significantly lower
      wear volumes and rates, and hence lower volumetric concentrations of wear
      particles, compared with the clinical MOM prosthesis. The substantially lower ion
      concentration released by these surface-engineered components provides important
      evidence to support the clinical application of this technology.

PMID- 12206519
TI  - Analysis of contact mechanics in ceramic-on-ceramic hip joint replacements.
AB  - The contact mechanics in ceramic-on-ceramic hip implants has been analysed in
      this study using the finite element method. Only the ideal conditions where the
      contact occurs within the acetabular cup were considered. It has been shown that
      the contact pressure distribution and the contact area at the main articulating
      bearing surfaces depend largely on design parameters such as the radial clearance
      between the femoral head and the acetabular cup, as well as the thickness of the
      ceramic insert. For the ceramic-on-ceramic hip implants used in clinics today,
      with a minimum 5-mm-thick ceramic insert, it has been shown that the radius of
      the contact area between the femoral head and the acetabular cup is relatively
      small compared with that of the femoral head and the ceramic insert thickness.
      Consequently, Hertz contact theory can be used to estimate the contact parameters
      such as the maximum contact pressure and the contact area.

PMID- 12206520
TI  - Effects of acetabular resurfacing component material and fixation on the strain
      distribution in the pelvis.
AB  - A 3D finite element (FE) model of an implanted pelvis was developed as part of a
      project investigating an all-polymer hip resurfacing design. The model was used
      to compare this novel design with a metal-on-metal design in current use and a
      metal-on-polymer design typical of early resurfacing implants. The model included
      forces representing the actions of 22 muscles as well as variable cancellous bone
      stiffness and variable cortical shell thickness. The hip joint reaction force was
      applied via contact modelled between the femoral and acetabular components of the
      resurfacing prosthesis. Five load cases representing time points through the gait
      cycle were analysed. The effect of varying fixation conditions was also
      investigated. The highest cancellous bone strain levels were found at mid-stance,
      not heel-strike. Remote from the acetabulum there was little effect of prosthesis
      material and fixation upon the von Mises stresses and maximum principal strains.
      Implant material appeared to have little effect upon cancellous bone strain
      failure with both bended and unbonded bone-implant interfaces. The unbonded
      implants increased stresses in the subchondral bone at the centre of the
      acetabulum and increased cancellous bone loading, resembling behaviour obtained
      previously for the intact acetabulum.

PMID- 12206521
TI  - Ride quality evaluation of an actively-controlled stretcher for an ambulance.
AB  - This study considers the subjective evaluation of ride quality during ambulance
      transportation using an actively-controlled stretcher (ACS). The ride quality of
      a conventional stretcher and an assistant driver's seat is also compared. Braking
      during ambulance transportation generates negative foot-to-head acceleration in
      patients and causes blood pressure to rise in the patient's head. The ACS absorbs
      the foot-to-head acceleration by changing the angle of the stretcher, thus
      reducing the blood pressure variation. However, the ride quality of the ACS
      should be investigated further because the movement of the ACS may cause motion
      sickness and nausea. Experiments of ambulance transportation, including rapid
      acceleration and deceleration, are performed to evaluate the effect of
      differences in posture of the transported subject on the ride quality; the
      semantic differential method and factor analysis are used in the investigations.
      Subjects are transported using a conventional stretcher with head forward, a
      conventional stretcher with head backward, the ACS, and an assistant driver's
      seat for comparison with transportation using a stretcher. Experimental results
      show that the ACS gives the most comfortable transportation when using a
      stretcher. Moreover, the reduction of the negative foot-to-head acceleration at
      frequencies below 0.2 Hz and the small variation of the foot-to-head acceleration
      result in more comfortable transportation. Conventional transportation with the
      head forward causes the worst transportation, although the characteristics of the
      vibration of the conventional stretcher seem to be superior to that of the ACS.

PMID- 12206522
TI  - The validity of using a video-based motion analysis system for measuring maximal
      area of fingertip motion and angular variation.
AB  - The aim of the study was to verify the application of a three-dimensional video
      motion analysis system to evaluate maximal fingertip motion area and angular
      variation of the hand by comparison and correlation with videofluoroscopic
      analysis. Eight normal subjects were recruited in this study. The maximal motion
      area of the fingertip and the angles of the metacarpal phalangeal (MP), proximal
      interphalangeal (PIP) and distal interphalangeal (DIP) joints in performing five
      sequential postures for functional evaluation of the hand were measured using a
      video motion analysis system and a fluoroscopy system respectively. The results
      indicated that the intraclass correlation coefficient (ICC) of the calculated
      maximal fingertip motion area between the two methods was 0.9597. The ICC for
      total active motion (TAM) measurements of three finger joints was 0.940 between
      the surface and bony landmarks by fluoroscopy, 0.952 between the surface
      landmarks from fluoroscopy and motion analysis, and 0.927 between the bony
      landmark from fluoroscopy and surface markers from motion analysis. The ICC for
      angular measurements between three different paired assessments was 0.9650,
      0.8896 and 0.8799 for the MP, PIP and DIP joints respectively. The results
      indicate that motion analysis is a practical method for assessing impairment of
      the hand.

PMID- 12206523
TI  - Subsidence in impaction grafting: the effect of adding a ceramic bone graft
      extender to bone.
AB  - The incidence of revision total hip arthroplasty is increasing dramatically and
      the associated demand for allograft bone is likely to exceed the available
      supply. In addition, allograft presents potential problems with regard to
      infection, antigenicity, availability, reproducibility and cost. It is therefore
      desirable to develop an alternative to allograft. This study investigated
      BoneSave, a porous tricalcium phosphate-hydroxyapatite ceramic for use in
      impaction grafting of the femur at revision total hip arthroplasty. The findings
      of an in vitro mechanical study comparing the initial stability of pure
      allograft, a volume mixture of 50 per cent allograft and 50 per cent BoneSave,
      and a volume mixture of 10 per cent allograft and 90 per cent BoneSave are
      reported. The BoneSave-allograft mixtures exhibit both much greater mechanical
      stability and reproducibility than the pure allograft (p < 0.05) at all tested
      loads (200-800 N). At high peak loads the high volume (90%, v/v) BoneSave mix
      also provided higher mechanical stability than the medium volume (50 per cent
      BoneSave-50 per cent allograft) mix (p < 0.05). These results demonstrate
      thatfrom a mechanical standpoint the tested ceramic provides adequate initial
      stability to be used as a bone graft extender with allograft in impaction
      grafting of the femur.

PMID- 12206524
TI  - Fracture mechanics analysis of the dentine-luting cement interface.
AB  - The objectives of this study were to determine the fracture toughness of adhesive
      interfaces between dentine and clinically relevant, thin layers of dental luting
      cements. Cements tested included a conventional glass-ionomer, F (Fuji 1), a
      resin-modified glass-ionomer, FP (Fuji Plus) and a compomer cement, D
      (DyractCem). Ten miniature short-bar chevron notch specimens were manufactured
      for each cement, each comprising a 40 microm thick chevron of lute, between two
      1.5 mm thick blocks of bovine dentine, encased in resin composite. The
      interfacial K(IC) results (MN/m3/2) were median (range): F; 0.152 (0.14-0.16),
      FP; 0.306 (0.27-0.37), D; 0.351 (0.31-0.37). Non-parametric statistical analysis
      showed that the fracture toughness of F was significantly lower (p <0.05) than
      those of FP or D, and all were significantly lower than values for monolithic
      cement specimens. Scanning electron microscopy of the specimens suggested crack
      propagation along the interface. However, energy dispersive X-ray analysis
      indicated that failure was cohesive within the cement. It is concluded that the
      fracture toughness of luting cement was lowered by cement-dentine interactions.

PMID- 12206525
TI  - Tunnel vision to tunnel mind.

PMID- 12206526
TI  - Achromatic transparency and the role of local contours.
AB  - In this paper we investigate the role of contours and junctions in the perception
      of single-plane achromatic transparency. In order to measure the accuracy with
      which observers encode transparency, a six-luminance stimulus was employed in
      which the figural properties could be easily manipulated. Accuracy was measured
      by requiring subjects to select (either by the method of adjustment or by using a
      forced-choice procedure) the luminance that best completed a simulated
      transparent filter. The X junctions in the stimulus were destroyed or perturbed
      in three experiments. Simple occlusion of the junction (experiment 1), and
      perturbation of the orientation of the contours of the filter as they pass
      through the junction (experiment 3) resulted in small but significant reductions
      in performance. On the other hand, a sudden change in orientation of the
      background (material) contours (experiment 2) resulted in a small but significant
      enhancement of overall performance compared with the control stimulus. In the
      forced-choice task, reversals in the polarity of contours (as defined by the
      brightness order of flanking regions) around the junction were shown to effect
      large changes in subjects' accuracy in processing transparency. The overall
      results show that X and Psi junctions are indeed salient properties of
      transparent stimuli. The findings suggest that jagged contours with sudden
      changes in direction are more likely to be attributed to reflectance (material)
      changes than to changes due to a transparent filter (or to illumination).

PMID- 12206527
TI  - Rapid long lasting learning in a collinear edge-detection task.
AB  - We have developed a detection task in which subjects identify a pair of collinear
      edges in a field of polygons. Five of our six subjects showed significant, rapid
      learning at this task. Four showed evidence of retention a day and a week later.
      In several transfer tests, we found that disruption of the distractors produced a
      significant drop-off in performance. These results are consistent with a model in
      which collinear targets initially produce a salience signal too weak to be
      reliably detected over the noise of the distractors. As the experiment proceeds,
      the visual system learns to dampen the distractor signals, allowing for more
      reliable detection.

PMID- 12206528
TI  - Absolute and relative effects of similarity and distance on grouping.
AB  - Four experiments are reported, the aim of which was to explore the achromatic
      colour and distance relations that determine the probability of achromatic
      surfaces grouping perceptually. The first two experiments were performed to test
      Wertheimer's conjecture that similarity and dissimilarity of achromatic colours
      jointly determine grouping. The results indicate that only similarity of
      achromatic colours determines grouping. Data from the other two experiments show
      that grouping is determined by absolute, relative, and Gillam's distances. These
      findings agree with previous literature showing that different algorithms or
      mechanisms determine grouping by similarity and grouping by distance.
      Additionally, these findings show that the single factor of grouping by distance
      also depends on multiple algorithms or mechanisms.

PMID- 12206529
TI  - How context influences predominance during binocular rivalry.
AB  - Variations in the predominance of an object engaged in binocular rivalry may
      arise from variations in the durations of dominance phases, suppression phases,
      or both. Earlier work has shown that the predominance of a binocular rival target
      is enhanced if that target fits well-via common color, orientation, or motion
      with its surrounding objects. In the present experiments, the global context
      outside of the region of rivalry was changed during rivalry, to learn whether
      contextual information alters the ability to detect changes in a suppressed
      target itself. Results indicate that context will maintain the dominance of a
      rival target, but will not encourage a suppressed target to escape from
      suppression. Evidently, the fate of the suppressed stimulus is determined by
      neural events distinct from those responsible for global organization during
      dominance. To reconcile diverse findings concerning rivalry, it may be important
      to distinguish between processes responsible for selection of one eye's input for
      dominance from processes responsible for the implementation and maintenance of
      suppression.

PMID- 12206530
TI  - Buildup and decay of a three-dimensional rotational aftereffect obtained with a
      three-dimensional figure.
AB  - Gaps in past literature have raised questions regarding the kinds of stimuli that
      can lead to three-dimensional (3-D) rotation aftereffects. Further, the
      characteristics of the buildup and decay of such aftereffects are not clear. In
      the present experiments, rotation aftereffects were generated by projections of
      cube-like stimuli whose dynamic perspective motions gave rise to the perception
      of rotation in unambiguous directions; test stimuli consisted of similar cubes
      whose rotation directions were ambiguous. In experiment 1, the duration of the
      adaptation stimulus was varied and it was found that the 3-D rotation aftereffect
      develops with a time constant of approximately 26 s. In experiment 2, the
      duration between adaptation and testing was varied. It was found that the 3-D
      rotation aftereffect has a decay constant of about 9 s, similar to that observed
      with 2-D motion aftereffects. Experiment 3 showed that the rotation aftereffects
      were not simple depth aftereffects. To account for these aftereffects and related
      data, a modification of an existing neural-network model is suggested.

PMID- 12206531
TI  - Active versus passive processing of biological motion.
AB  - Johansson's point-light walker figures remain one of the most powerful and
      convincing examples of the role that motion can play in the perception of form
      (Johansson, 1973 Perception & Psychophysics 14 201 - 211; 1975 Scientific
      American 232(6) 76 - 88). In the current work, we use a dual-task paradigm to
      explore the role of attention in the processing of such stimuli. In two
      experiments we find striking differences in the degree to which direction
      discrimination performance in point-light walker displays appears to rely on
      attention. Specifically, we find that performance in displays thought to involve
      top-down processing, either in time (experiment 1) or space (experiment 2) is
      adversely affected by dividing attention. In contrast, dividing attention has
      little effect on performance in displays that allow low-level, bottom-up
      computations to be carried out. We interpret these results using the
      active/passive motion distinction introduced by Cavanagh (1991 Spatial Vision 5
      303-309).

PMID- 12206532
TI  - Lateralization of narrow-band noise by blind and sighted listeners.
AB  - The effects of varying interaural time delay (ITD) and interaural intensity
      difference (IID) were measured in normal-hearing sighted and congenitally blind
      subjects as a function of eleven frequencies and at sound pressure levels of 70
      and 90 dB, and at a sensation level of 25 dB (sensation level refers to the
      pressure level of the sound above its threshold for the individual subject).
      Using an 'acoustic' pointing paradigm, the subject varied the IID of a 500 Hz
      narrow-band (100 Hz) noise (the 'pointer') to coincide with the apparent lateral
      position of a 'target' ITD stimulus. ITDs of 0, +/-200, and +/-400 micros were
      obtained through total waveform delays of narrow-band noise, including envelope
      and fine structure. For both groups, the results of this experiment confirm the
      traditional view of binaural hearing for like stimuli: non-zero ITDs produce
      little perceived lateral displacement away from 0 IID at frequencies above 1250
      Hz. To the extent that greater magnitude of lateralization for a given ITD,
      presentation level, and center frequency can be equated with superior
      localization abilities, blind listeners appear at least comparable and even
      somewhat better than sighted subjects, especially when attending to signals in
      the periphery. The present findings suggest that blind listeners are fully able
      to utilize the cues for spatial hearing, and that vision is not a mandatory
      prerequisite for the calibration of human spatial hearing.

PMID- 12206533
TI  - Spatial stimulus cue information supplying auditory saltation.
AB  - Auditory saltation is a misperception of the spatial location of repetitive,
      transient stimuli. It arises when clicks at one location are followed in perfect
      temporal cadence by identical clicks at a second location. This report describes
      two psychophysical experiments designed to examine the sensitivity of auditory
      saltation to different stimulus cues for auditory spatial perception. Experiment
      1 was a dichotic study in which six different six-click train stimuli were used
      to generate the saltation effect. Clicks lateralised by using interaural time
      differences and clicks lateralised by using interaural level differences produced
      equivalent saltation effects, confirming an earlier finding. Switching the
      stimulus cue from an interaural time difference to an interaural level difference
      (or the reverse) in mid train was inconsequential to the saltation illusion.
      Experiment 2 was a free-field study in which subjects rated the illusory motion
      generated by clicks emitted from two sound sources symmetrically disposed around
      the interaural axis, ie on the same cone of confusion in the auditory hemifield
      opposite one ear. Stimuli in such positions produce spatial location judgments
      that are based more heavily on monaural spectral information than on binaural
      computations. The free-field stimuli produced robust saltation. The data from
      both experiments are consistent with the view that auditory saltation can emerge
      from spatial processing, irrespective of the stimulus cue information used to
      determine click laterality or location.

PMID- 12206534
TI  - Evidence for transliminality from a subliminal card-guessing task.
AB  - In this experiment we sought to provide evidence for transliminality from a test
      of subliminal perception that was disguised as a computerised ESP card-guessing
      task. It was predicted that highly transliminal individuals would outperform
      those with low levels of transliminality when given subliminal primes or 'clues'
      to the correct choice of card, but not when no primes were given. In line with
      the prediction, higher levels of transliminality were found to be associated with
      a greater number of correct selections of the target card on the primed trials,
      but not on the unprimed trials. In addition, a positive correlation was obtained
      between transliminality and detection accuracy, suggesting that higher levels of
      transliminality are associated with a greater sensitivity to visual stimulation.
      The results are discussed with reference to the possibility that transliminality
      might offer an alternative explanation for some ostensibly psychic perceptual
      experiences if subliminally acquired material is wrongly attributed to psychic
      sources.

PMID- 12206535
TI  - Last but not least. Foreshortening gives way to forelengthening.

PMID- 12206536
TI  - A boycott by passport.

PMID- 12206537
TI  - The future of psychoanalytic research: turning points and new opportunities.

PMID- 12206538
TI  - Where's the text? The problem of validation in psychoanalysis.
AB  - Whatever their differences, the various schools of psychoanalysis all subscribe
      to the case study, based on clinical vignette and anecdote, as the "text" of
      psychoanalysis. Because the typical case study presents not the actual analytic
      dialogue but a reconstruction based on the analyst's selective memory, the use of
      such a text renders problematic the validation of an analyst's case formulation,
      and has traditionally diminished the epistemological status of psychoanalysis.
      Pristine clinical data, as would be provided by verbatim transcripts of audio
      recorded analytic sessions, are rarely created and even more rarely made public.
      Study of the psychoanalytic process is thereby made impossible, whether by
      clinical exegesis, qualitative analysis, or quantitative statistical analysis.
      Yet the analytic community, highly resistant to this public documentation,
      continues to marshal five common arguments against it. These arguments are
      reviewed and responded to in the belief that such documentation would enhance the
      field's intellectual status by allowing the problem of clinical validation to be
      addressed in ways that move beyond appeals to the authority of private clinical
      experience.

PMID- 12206539
TI  - A new language for psychoanalytic diagnosis.
AB  - Many psychoanalysts believe it is impossible to conduct empirical research
      without eviscerating or trivializing psychoanalytic constructs, and past research
      efforts have all too often reinforced this view. A new method for studying
      personality and personality pathology is presented that challenges such beliefs.
      This method, the Shedler-Westen Assessment Procedure (SWAP), captures the
      richness and complexity of psychoanalytic constructs and formulations while also
      providing reliable data for research. The method is being used to develop a new
      personality disorder taxonomy, as an alternative to the DSM, that is both
      empirically grounded and psychoanalytically relevant. Its role in psychoanalytic
      training and supervision is discussed, as is its value as a measure of structural
      change in psychoanalytic process and outcome research.

PMID- 12206540
TI  - Quantitative research on the primary process: method and findings.
AB  - Freud always defined the primary process metapsychologically, but he described
      the ways it shows up in dreams, parapraxes, jokes, and symptoms with enough
      observational detail to make it possible to create an objective, reliable scoring
      system to measure its manifestations in Rorschach responses, dreams, TAT stories,
      free associations, and other verbal texts. That system can identify signs of the
      thinker's efforts, adaptive or maladaptive, to control or defend against the
      emergence of primary process. A prerequisite and a consequence of the research
      that used this system was clarification and elaboration of the psychoanalytic
      theory of thinking. Results of empirical tests of several propositions derived
      from psychoanalytic theory are summarized. Predictions concerning the method's
      most useful index, of adaptive vs. maladaptive regression, have been repeatedly
      verified: People who score high on this index (who are able to produce well
      controlled "primary products" in their Rorschach responses), as compared to those
      who score at the maladaptive pole (producing primary-process-filled responses
      with poor reality testing, anxiety, and pathological defensive efforts), are
      better able to tolerate sensory deprivation, are more able to enter special
      states of consciousness comfortably (drug-induced, hypnotic, etc.), and have
      higher achievements in artistic creativity, while schizophrenics tend to score at
      the extreme of maladaptive regression. Capacity for adaptive regression also
      predicts success in psychotherapy, and rises with the degree of improvement after
      both psychotherapy and drug treatment. Some predictive failures have been
      theoretically interesting: Kris's hypothesis about creativity and the controlled
      use of primary process holds for males but usually not for females. This body of
      work is presented as a refutation of charges, brought by such critics as Crews,
      that psychoanalysis cannot become a science.

PMID- 12206541
TI  - The priority of primary process categorizing: experimental evidence supporting a
      psychoanalytic developmental hypothesis.
AB  - Earlier work has provided experimental evidence for the existence of the primary
      and secondary process mental organization posited by Freud and has demonstrated
      that primary process effects are the more active unconsciously (Brakel et al.
      2000). Primary and secondary processes were assessed by a categorization test in
      which qualitatively different principles could be used. In new experiments using
      the same stimuli, another significant implication of Freud's model was tested:
      that primary process mental organization has developmental priority. In these
      experiments, which studied 559 participants ranging in age from 3 to 80, it was
      found (1) that primary process mentation predominates in preschoolers; (2) that
      it is not until around age 7 that primary process organization is supplanted by
      secondary process organization; and (3) that after age 7 the predominance of
      secondary process organization remains remarkably stable throughout the life
      span.

PMID- 12206542
TI  - Mourning analysis: the post-termination phase.
AB  - One hundred twenty-one analytic candidates who had completed training analysis
      responded to a survey about their post-termination experience. Seventy-six
      percent of respondents experienced a mourning process that lasted on average
      between six months and a year, while 24 per cent experienced no discernible sense
      of painful loss. Twenty candidates were interviewed to obtain a deeper
      understanding of the mourning process that follows analysis. During the post
      termination phase, the analysand's self-analytic capacity is tested in the
      struggle to contain and understand feelings about the loss of the analyst, as
      well as transference reactions triggered by that loss. After a "good-enough
      analysis," the analysand internalizes not only the analyst's functions and
      attitudes toward him or her, but also a sustaining, positive internal image of
      the analyst. Four cases illustrate unexpected difficulties that may emerge during
      the post-termination phase when the loss of the analyst is experienced as a
      repetition of earlier, traumatic losses or as a rupture of an unanalyzed,
      selfobject transference.

PMID- 12206543
TI  - Defining character integrity.
AB  - Previous work on the integrity of character is reviewed and a contemporary
      definition offered using concepts of subordinate and supraordinate
      schematizations of self and relationships with others. The definition is
      clarified by a developmental perspective on possible growth in character
      integrity over the life cycle. Three types are defined by patterns in sense of
      identity, object relations, and defensive control of emotion. Such type
      formulations are useful because technique can be varied according to the inferred
      level of character integrity.

PMID- 12206544
TI  - Psychoanalytic patients in the U.S., CANADA, and Australia: I. DSM-III-R
      disorders, indications, previous treatment, medications, and length of treatment.
AB  - To determine the demographics, DSM-III-R disorders diagnosed, indications used in
      recommending psychoanalysis, previous treatment histories, use of medication, and
      length of treatment in patients in psychoanalysis in the U.S., Canada, and
      Australia, a mail survey of practice was sent to every other active member of the
      American Psychoanalytic Association and every member of the Australian
      Psychoanalytical Society. This supplemented an earlier survey sent to all Ontario
      psychoanalysts. The response rates were 40.1 % (n = 342) for the U.S., 67.2% (n =
      117) for Canada, and 73.9% (n = 51) for Australia. Respondents supplied data on
      1,718 patients. The employment rate for patients increases as analysis progresses
      (p < .0001). The mean number of concurrent categories of disorders (Axis I, Axis
      II, and Disorders First Evident in Childhood) per patient at the start of
      treatment is 5.01 (SD = 3.66; median = 4; mode = 3). There are no statistically
      significant differences across countries. Mood, anxiety, sexual dysfunction, and
      personality disorders are most common. American Psychiatric Association /
      American Psychoanalytic Association peer review criteria for indicating
      psychoanalysis are followed for 86.5% of patients. Over 80% of patients in all
      three countries had undergone previous treatments prior to analysis. In the U.S.,
      18.2% of analysands are on concurrent psychoactive medication; in Australia,
      9.6%. The mean length of analyses conducted in the U.S. is 5.7 years, in
      Australia 6.6, and in Canada 4.8. Psychoanalytic patients in all three countries
      have similar rates of DSM-III-R psychopathology, and many indications of
      chronicity.

PMID- 12206545
TI  - Psychoanalytic patients in the U.S., Canada, and Australia: II. A DSM-III-R
      validation study.
AB  - A study was conducted to validate our previous work on the DSM-III-R disorders
      diagnosed in patients in psychoanalysis in the U.S., Canada, and Australia and to
      determine which specific mood, anxiety, and personality disorders were the most
      common in these patients. The earlier study consisted of three surveys of
      psychoanalytic practice that together obtained data on 1,718 patients, through
      extensive mail surveys to analysts in the three countries. In the validation
      study, 206 patients were diagnosed using a different technique. Analysts similar
      in important respects to those who participated in the original surveys rated
      patients diagnostically before and after DSM-III-R training. After training, no
      significant changes appeared in the rates for any of the specific mood disorders.
      For the thirty disorders examined, training effects decreased the identification
      of the generalized anxiety disorder, and increased the identification of three
      personality disorders: avoidant, dependent, and personality disorder not
      otherwise specified. Thus, analysts slightly underdiagnosed the number of
      personality disorders, and some "anxious" patients appear to have qualified for
      personality disorders. Some limitations of the DSM-III-R notion of narcissistic
      personality are discussed, as are the importance and stability of the self
      defeating (masochistic) personality disorder. The most common Axis I disorder in
      psychoanalytic patients was dysthymia, followed by major depression, recurrent.
      This study reinforces the findings of the original three surveys. Minor
      corrections were developed to adjust the original three surveys.

PMID- 12206546
TI  - Current perspectives on the goals of psychoanalysis. Panel report.

PMID- 12206547
TI  - Wallerstein on lay analysis and the lawsuit.

PMID- 12206548
TI  - Schmidt-Hellerau on Greenberg's new look.

PMID- 12206549
TI  - Kantrowitz on her Greenberg commentary.

PMID- 12206550
TI  - Schwaber on Meissner and psychic reality.

PMID- 12206551
TI  - Percutaneous aortic valvoplasty in congenital aortic valvar stenosis.

PMID- 12206552
TI  - Mitral valvar prolapse: overlap or masked syndrome?

PMID- 12206553
TI  - Current insights in diagnosis and management of the cardiovascular complications
      of Marfan's syndrome.
AB  - Marfan's syndrome is an inherited disorder of connective tissue, caused by
      mutations in the fibrillin-1 gene located on chromosome 15. Diagnosis is still
      based on a combination of major and minor clinical features. Prognosis is mainly
      determined by the cardiovascular complications. Advances in surgical and medical
      treatment for these complications have dramatically improved the prognosis of the
      syndrome.

PMID- 12206554
TI  - Percutaneous aortic valvoplasty in congenital aortic valvar stenosis.
AB  - OBJECTIVE: To evaluate immediate and midterm results with percutaneous aortic
      valvoplasty. MATERIAL AND METHODS: We reviewed the records of 141 patients
      undergoing percutaneous aortic valvopasty over a period of 13 years. RESULTS: The
      patients were aged from 2 months to 40 years, with a mean of 10.9 +/- 9.9 years.
      Of the total, 90 (63+/%) were male. The initial systolic peak-to-peak gradient
      decreased from 163 +/- 52 mmHg to 32 +/- 18 mmHg (p < 0.01) after valvoplasty in
      all 141 patients, while the proportional reduction ranged from 0 to 100%, with a
      mean of 72 +/- 27%. The index of the size of the balloon to the diameter of the
      valvar orifice was 0.88 +/- 0.19 in 128 patients. The follow-up ranged from 6 to
      168 months, with a mean 51 +/- 48 months in 70 patients. A significant difference
      was found in those failing after dilation when the initial evaluation was
      compared to the final evaluation of patients with follow-up. In those failing,
      the number of patients rose from 12 (17%) to 21 (30%) (p < 0.01). In contrast, in
      those in whom we achieved success, there was not such a great difference between
      the initial and final evaluation: 58 (83%) versus 49 (70%) (p < 0.1). The
      actuarial freedom curve of patients not needing new percutaneous aortic
      valvoplasty or surgery, by 182 months, was at 87% and 82% respectively.
      CONCLUSION: We have reviewed the largest series of patients in Latin-America
      reported thus far after undergoing percutaneous aortic valvoplasty, concentrating
      on mid term follow-up and limitations. New prospective and multicentric studies
      are needed from our region.

PMID- 12206555
TI  - A prospective study to determine the significance of ventricular late potentials
      in children with mitral valvar prolapse.
AB  - We aimed prospectively to determine the incidence of ventricular arrhythmias and
      ventricular late potentials in children with mitral valvar prolapse, and to
      assess whether signal-averaged electrocardiography could identify which such
      children were at high risk of developing ventricular tachycardia. In all, we
      examined 151 children with mitral valvar prolapse, at an age of 12.2 +/- 3.1
      years, and 164 healthy subjects aged 12.3 +/- 3.7 years. All children underwent
      24-hour ambulatory Holter monitoring and echocardiography. The children with
      mitral valvar prolapse were followed prospectively for a mean of 64 months. There
      was a significantly higher prevalence of ventricular arrhythmias in those with
      prolapse than in the controls (p < 0.0001). Runs of ventricular tachycardia were
      observed in 3 children with mitral valvar prolapse compared with one from the
      control group. Late potentials were more frequently observed in the children with
      mitral valvar prolapse than in those who were healthy (p < 0.0001), and also in
      those with prolapse suffering ventricular arrhythmias compared with those without
      ventricular arrhythmias (p < 0.02). During follow-up, 24 children with prolapsing
      mitral valves developed non-sustained ventricular tachycardia, giving a frequency
      of 3.1/100 subject-years. The sensitivity of late potentials was low, at 52%, for
      the identification of children with mitral valvar prolapse who developed
      ventricular tachycardia, although the specificity was high at 90%. This gave a
      positive predictive value of 50%, and a negative predictive value of 91%. We
      conclude that prolapse of the mitral valve predisposes to the development of
      ventricular arrhythmias and late potentials in children. An abnormal signal
      averaged electrocardiogram is a specific, but not very sensitive, predictor for
      the development of ventricular tachycardia in such children.

PMID- 12206556
TI  - Cineangiographic aortic dimensions in normal children.
AB  - Knowledge of normal aortic dimensions is important in the management of children
      with aortic disease. So as to define such dimensions, we undertook a
      retrospective review of clinical data and aortic cineangiograms from 167 subjects
      without aortic disease having a mean age of 3.67 years, with a range from 0.01 to
      14.95 years. Amongst the patients, 56 were without detectable cardiac lesions, 66
      patients had mild pulmonary stenosis, 30 were seen with Kawasaki disease, and 15
      with small interatrial defects within the oval fossa. Aortograms were available
      in all. No patient had any hemodynamic derangement that would have affected the
      aorta during intrauterine life or childhood. Systolic dimensions were measured in
      the ascending and descending aorta at the level of the carina, at the transverse
      aortic arch distal to the brachiocephalic, of the left common carotid artery at
      its origin, at the transverse aortic arch distal to the left common carotid
      artery, at the aortic isthmus, and of the aorta at the level of the diaphragm. A
      regression analysis model was used to establish the range of predicted normal
      values, with their confidence limits, standardizing the values to height as the
      biophysical parameter having the highest correlation to aortic dimensions. Normal
      ranges were established for all the levels of measurement. The data should prove
      useful in identifying abnormalities of the thoracic aorta during childhood, and
      when assessing the outcomes of interventions.

PMID- 12206557
TI  - Influence of early repair of tetralogy of fallot without an outflow patch on late
      arrhythmias and sudden death: a 27-year follow-up study following a uniform
      surgical approach.
AB  - Pulmonary regurgitation and older age at the time of repair may have a large
      impact late after repair on subsequent mortality of patients with tetralogy of
      Fallot. We aimed to identify whether age at repair, and preservation of the
      pulmonary valve, had a favorable influence on morbidity and mortality. We also
      analyzed risk factors for late death subsequent to surgical repair. We identified
      167 patients who, between 1965 and 1975, and at a mean age of 6 years, underwent
      total repair of tetralogy of Fallot by a single surgical team without use of an
      outflow patch. All patients were known to have survived for at least 30 days
      after repair, and late mortality was identified though the use of hospital
      records, interviews, and death certificates. The 29-year actuarial survival rate
      was 86%, with 24 late deaths. Of these deaths, seven occurred suddenly (4.2%).
      Morbidity was analyzed in 99 of the patients by means of a written questionnaire
      and telephone interview. It proved possible to analyze ventricular and valvar
      function in 50 of the patients. Survivors experienced no re-intervention, and 89%
      of them were in class I of the grading system of the New York Heart Association.
      We found evidence of 3 episodes of sustained ventricular tachycardia (3.0%), and
      two episodes of atrial tachycardia (2.0%). Of the 50 patients in whom serial
      examinations were available, 18 had pulmonary regurgitation of moderate degree or
      greater, and none had more than moderate tricuspid regurgitation, with a mean QRS
      duration of 148 ms and an ejection fraction for the left ventricle of 50%. Older
      age at repair (p = 0.03), and longer periods of cardiac arrest during repair (p =
      0.02), were associated with late mortality. Although the mortality was similar to
      that observed in previous reports, our operative method might have a better
      effect in terms of late morbidity.

PMID- 12206558
TI  - Transcatheter closure of atrial septal defects in the oval fossa: is the method
      applicable in small children?
AB  - We report our experience from 1996 through 1999, representing our initial
      experience with use of the Amplatzer device to close atrial septal defects. Of 46
      patients taken to the catheter laboratory with the intention to close the defect,
      the device was permanently implanted in 40 (87%). They were aged between 1.4 and
      71.8 years, with weights ranging from 7.8 to 90 kg. Both age and weight
      distributed into two peaks, demonstrating two different populations. The size of
      the devices, taking the biggest device if two were inserted, was between 9 and 30
      mm. We underwent a short learning curve, but the time required for fluoroscopy,
      or the number of difficulties experienced, showed no connection with the size or
      age of the patient, nor the size of the defect itself. A suspicion that young age
      and small size would increase the risk and difficulties, and result in more
      interrupted procedures, could not be substantiated. In children no interruption
      was procedural. Our early experience, therefore, demonstrates that an experienced
      interventional team can use the Amplatzer occluder successfully to close atrial
      septal defects in patients of all ages and sizes, at least from 7.8 kg and up.

PMID- 12206559
TI  - Closure of ventricular septal defects: a study of factors influencing spontaneous
      and surgical closure.
AB  - INTRODUCTION: Aspects of the management of ventricular septal defects which
      remain uncertain include the role of screening, and the need for closure of
      defects that remain patent. AIM: To ascertain the natural history of clinically
      significant ventricular septal defects, and to examine uncertainties in
      strategies of management. METHODS: We studied prospectively a regional cohort of
      children born with isolated ventricular septal defects, noting age at
      presentation; sex; morphology and size of the defect; age at closure, if it
      occurred, and the means of closure. RESULTS: We identified 290 children with
      isolated ventricular septal defects, of whom 147 (51%) were male. The mean follow
      up period was 65 months, with five cases being lost to follow up. Surgical
      closure was required in 41 (14%) cases, and 155 (54%) defects closed
      spontaneously. Spontaneous closure occurred in 123 (68%) out of 180 cases with
      completely muscular borders, and in 31 (29%) of the 107 patients with
      perimembranous defects. There were two cases with associated aortic regurgitation
      and no cases of endocarditis. Size and morphology of the defect were significant
      predictors of spontaneous and surgical closure. In addition, young age at
      diagnosis was a significant predictor of spontaneous closure. CONCLUSIONS: The
      size and morphology of a ventricular septal defect are important determinants of
      spontaneous closure and to the need for surgical intervention. Early age at
      presentation, in contrast, is not predictive of the need for surgical
      intervention. In early childhood, there appears to be very little risk of
      endocarditis or aortic valvar prolapse. Neither screening of populations to
      identify ventricular septal defects, nor surgical closure of asymptomatic defects
      in childhood, are supported by our findings.

PMID- 12206560
TI  - Interatrial communication through the mouth of the coronary sinus.
AB  - OBJECTIVES: We describe the structure of, and suggest an etiology for, the
      interatrial communication which can occur through the mouth of the coronary
      sinus. Based on the study of human embryos, we propose that the defect is best
      explained by dissolution of the wall of the coronary sinus adjacent to the left
      atrium, permitting shunting between the atriums through the right atrial orifice
      of the sinus. BACKGROUND: An interatrial communication across the mouth of the
      coronary sinus defect was first described in 1965 by Raghib and colleagues, its
      existence being predicated on the basis of incomplete formation of the left
      "atriovenous fold". Their hypothesis implies that the coronary sinus never
      develops, and thus the atrial septum itself is incomplete. METHODS: We have
      studied the development of the coronary sinus in a series of human embryos. Based
      on this work, we present the anatomical findings in 6 specimens with varying
      degrees of dissolution of the walls of the coronary sinus, and ten specimens with
      isomerism of the right atrial appendages, in which the sinus has never been
      formed. RESULTS: The coronary sinus defect is not a hole within the atrial
      septum, but a communication between the atriums through the mouth of the sinus.
      There was a range of defects in our series of specimens with usual atrial
      arrangement, extending from complete absence of the walls which normally separate
      the coronary sinus from the left atrium, to small fenestrations between this
      vessel and the left atrial cavity. In the hearts with isomerism of the right
      atrial appendages, however, we never observed an orifice of the coronary sinus.
      Thus, a coronary sinus defect cannot exist in this setting. CONCLUSIONS: Our
      findings indicate that the defect requires initial formation of the walls of the
      coronary sinus, but with subsequent dissolution of the wall adjacent to the left
      atrium. This produces a communication between the atriums through the mouth of
      the sinus.

PMID- 12206561
TI  - Systemic-to-pulmonary blood supply in Tetralogy of Fallot with pulmonary atresia.
AB  - Tetralogy of Fallot with pulmonary atresia is one of the most challenging
      congenital cardiac malformations, for the morphologist, cardiologist and surgeon
      alike. Much of the difficulty in this lesion concerns the nature and development
      of pulmonary arterial supply, and the manner in which complete segmental supply
      to the lungs can be successfully restored or maintained. In this review, we
      discuss the anatomy and nomenclature of the lesion, emphasising the variability
      that can occur in pulmonary arterial anatomy, particularly in the presence of
      systemic-to-pulmonary collateral arteries. We speculate on the likely embryologic
      origins of these connections. Then by means of anatomic-clinical correlations, we
      emphasise the diagnostic approach to delineating the origin and extent of the
      pulmonary vasculature.

PMID- 12206562
TI  - Incomplete scimitar syndrome.

PMID- 12206563
TI  - Thrombotic obstruction of modified Blalock-Taussig shunt.

PMID- 12206564
TI  - Divided left atrium.

PMID- 12206565
TI  - Abraham Morris Rudolph.

PMID- 12206566
TI  - Twisted atrioventricular valves in double inlet left ventricle.
AB  - Twisted atrioventricular connections usually occur in hearts with biventricular
      artioventricular connections. Here, we describe a case of twisted
      atrioventricular valves associated with double inlet left ventricle and
      discordant ventriculo-arterial connections. Color Doppler echocardiography, and
      cine magnetic resonance imaging, clearly demonstrated that the right
      atrioventricular valve was located anterior and superior to the left
      atrioventricular valve, and that the axes of the two atrioventricular valves
      crossed each other within the dominant left ventricle.

PMID- 12206567
TI  - Creation with a stent of an unrestrictive lasting atrial communication.
AB  - A new technique is presented to create percutaneously an unrestrictive and
      lasting atrial communication in small children. In 2 infants, a stent was
      deployed in a restrictive atrial communication and first inflated with an 8 mm
      balloon. The stent was then further expanded up to 10 or 12 mm. The gradient and
      turbulent flow between the two atriums disappeared completely. The stent retained
      a very stable position without embolisation. Other complications, such as
      formation of thrombus or arrhythmia, were not observed until elective
      explantation after 2 and 11 months. We conclude that, in infants, dilation of the
      atrial septum with a stent can provide a safe, lasting, and unrestrictive atrial
      communication.

PMID- 12206568
TI  - Provision of services for rehabilitation of children and adolescents with
      congenital cardiac disease: a survey of centres for paediatric cardiology in the
      United Kingdom.
AB  - A postal questionnaire survey of the 17 centres for paediatric cardiology in the
      UK investigated the attitudes of staff towards rehabilitation and the current
      level of provision. The majority of respondents (82%) believed they should
      provide rehabilitation for their patients, but only one centre had a programme
      for rehabilitation. Few respondents (18%) believed they were meeting the needs of
      their patients' for rehabilitation. Major barriers to providing rehabilitation
      were funding and the wide geographical catchment areas.

PMID- 12206569
TI  - Acute myocardial infarction in the neonatal period.
AB  - We describe two neonates presenting with myocardial infarction, due to two
      different aetiologies of this extremely rare but potentially treatable condition,
      and discuss the management. One neonate had myocardial infarction complicating
      enteroviral myocarditis and recovered completely. The second had fatal myocardial
      infarction due to thrombosis of the left coronary artery. Although rare, the
      attending paediatrician should have a high index of suspicion when evaluating a
      neonate with acute onset of collapse. Electrocardiographic changes are
      diagnostic, but further echocardiographic assessment and prompt management at a
      tertiary cardiac centre are advised.

PMID- 12206570
TI  - Myocardial bridging of the anterior interventricular coronary artery in the
      setting of hypertrophic cardiomyopathy in children and adolescents.

PMID- 12206571
TI  - Use of the reliable change index to evaluate clinical significance in SF-36
      outcomes.
AB  - The SF-36 Health Survey is the most widely used self-report measure of functional
      health. It is commonly used in both randomized controlled trials (RCT) and non
      controlled evaluation of medical or other health services. However, determining a
      clinically significant change in SF-36 outcomes from pre-to-post-intervention, in
      contrast to statistically significant differences, is often not a focus of
      medical outcomes research. We propose use of the Reliable Change Index (RCI) in
      combination with SF-36 norms as one method for researchers, provider groups, and
      health care policy makers to determine clinically significant healthcare outcomes
      when the SF-36 is used as a primary measure. The RCI is a statistic that
      determines the magnitude of change score necessary of a given self-report measure
      to be considered statistically reliable. The RCI has been used to determine
      clinically significant change in mental health and behavioral medicine outcomes
      research, but is not widely applied to medical outcomes research. A usable table
      of RCIs for the SF-36 has been calculated and is presented. Instruction and a
      case illustration of how to use the RCI table is also provided. Finally,
      limitations and cautionary guidelines on using SF-36 norms and the RCI to
      determine clinically significant outcome are discussed.

PMID- 12206572
TI  - Reversible bronchial obstruction and disease-related health status in COPD.
AB  - We aimed to assess whether partially reversible and fixed airway obstructions are
      associated with different health status profiles of chronic obstructive pulmonary
      disease (COPD) patients. We characterized health status profiles of outpatients
      over 64 years suffering from COPD with fixed (n = 181) or partially reversible
      obstruction (n = 95) and from chronic bronchitis with forced expiratory volume in
      the first second (FEV1) > 69% of that predicted (n = 109) on the basis of the
      Saint George Respiratory Questionnaire (SGRQ) and indexes assessing cognitive
      (Mini Mental State), affective (15-item Geriatric Depression Scale) and physical
      status (Index of Barthel, six-minute walking test) and quality of sleep (Index of
      disturbed sleep). The degree of group-specificity of health status profiles was
      assessed by discriminant analysis. The 54.1% of COPD patients with partially
      reversible obstruction were recognized to have a distinctive health status
      profile characterized by a moderate to severe impairment of all components
      ('Symptoms', 'Activity', 'Impacts') of the SGRQ and of select indexes of
      performance. According to logistic regression analysis, this health status
      profile was associated with FEV < 46% of that predicted (odds ratio (OR): 1.6,
      95% confidence interval (CI): 1.07-2.38), the use of at least three respiratory
      drugs (OR: 2.28, CI: 1.46-3.57) and living alone (OR: 2.01, 95% CI: 1.3-2.29).
      COPD patients with fixed obstruction had a very heterogeneous health status.
      Research is needed to verify whether the unfavorable health status profile
      typical of a subset of COPD patients is associated with a distinctive prognosis
      and can be improved by dedicated therapeutic interventions.

PMID- 12206573
TI  - Reliability and validity of the COOP/WONCA health status measure in patients with
      chronic obstructive pulmonary disease.
AB  - The objective of the study was to assess the reliability and validity of the
      Dartmouth Primary Care Cooperative Information Project/World Organization of
      National Colleges, Academies, and Academic Associations of General
      Practice/Family Physicians (COOP/WONCA) questionnaire in outpatients with chronic
      obstructive pulmonary disease (COPD). The test-retest reliability of individual
      items of the COOP/WONCA questionnaire was assessed using a weighted kappa
      statistic, and construct validity was assessed by correlating items of the
      COOP/WONCA with the EQ-5D health status measure. Discriminant validity was
      assessed by comparing scores for known groups, at the same time comparing the
      results with those of a lung-specific health status questionnaire. The individual
      items of the COOP/WONCA had test-retest reliabilities of 0.67-0.78 (weighted
      kappa). Spearman's rank correlations between COOP/WONCA single-item scores and
      corresponding EQ-5D ranged 0.45-0.72, which were generally higher than
      associations between non-corresponding items. Four of the five COOP/WONCA items
      did not discriminate between patient groups divided according to forced
      expiratory flow in 1 sec (FEV1) in percent of predicted and 6-min walking
      distance, while four of five items of the lung-specific questionnaire
      discriminated well between these groups. The COOP/WONCA chart system was reliable
      and showed properties supporting the construct validity of the measure. The
      items, however, did not discriminate well between known groups, indicating that
      this questionnaire is not very sensitive in patients with COPD. The reliability
      of the COOP/WONCA items was acceptable for use at group level, but lower than
      current recommendations for use in individual patients.

PMID- 12206574
TI  - Development and validation of a short measure of health status for individuals
      with acute myocardial infarction: the myocardial infarction dimensional
      assessment scale (MIDAS).
AB  - The purpose of this study was to develop and validate a disease-specific health
      status measure for individuals with myocardial infarction (MI). The development
      of the myocardial infarction dimensional assessment scale (MIDAS) followed three
      main stages. Stage 1 consisted of in-depth, semi-structured, exploratory
      interviews conducted on a sample of 31 patients to identify areas of salience and
      concern to patients with MI. These interviews generated 48 candidate questions.
      In stage 2 the 48-item questionnaire was used in a postal survey to identify
      appropriate rephrasing/shortening, to determine acceptability and to help
      identify sub-scales of the instrument addressing different dimensions of MI.
      Finally, in stage 3 the construct validity of MIDAS subscales was examined in
      relation to clinical and other health outcomes. A single centre (district general
      hospital) in England was used for stages 1 and 3 and a national postal survey was
      conducted for stage 2. A total of 410 patients were recruited for the national
      survey (stage 2). Full data were available on 348 (85%) patients. One hundred and
      fifty-five patients were recruited to test construct validity (stage 3). The
      MIDAS contains 35 questions measuring seven areas of health status: physical
      activity, insecurity, emotional reaction, dependency, diet, concerns over
      medication and side effects. The measure has high face, internal and construct
      validity and is likely to prove useful in the evaluation of treatment regimes for
      MI.

PMID- 12206575
TI  - Changes in health related quality of life among patients treated for eating
      disorders.
AB  - OBJECTIVE: To prospectively investigate changes in the perception of health
      related quality of life (HRQoL) among eating disorder patients after 2 years of
      treatment and follow-up and clinical predictors of change. METHOD: One hundred
      and thirty-one consecutive subjects were recruited from an eating disorder
      outpatient clinic. Subjects completed a generic HRQoL questionnaire, the Short
      Form-36 (SF-36), as well as the Eating Attitudes Test (EAT-40) to measure symptom
      severity and the Hospital Anxiety and Depression scale (HAD), at the first visit
      and after 24 months. RESULTS: Perception of HRQoL, measured by the SF-36, showed
      significant improvement in all but the role emotional domain after 2 years. The
      greatest improvements were observed in the physical function and social function
      domains, followed by mental health and vitality. Despite significant improvement
      in the summary mental health scale, scores after 2 years of treatment and follow
      up were still below normative population values of women aged 18-34. Severity of
      eating disorder symptoms and presence of anxiety or depression at baseline
      significantly affected improvement in various SF-36 domains. CONCLUSIONS: Despite
      improvements in perception of HRQoL, eating disorder patients were more
      dysfunctional in all domains of the SF-36 even after 2 years of treatment and
      follow-up compared with women in the general population, and the severity of
      eating disorder symptoms was correlated with degree of dysfunction.

PMID- 12206576
TI  - Subjective quality of life in severely mentally ill patients: a comparison of two
      instruments.
AB  - Although many quality of life (QOL) scales have been developed, comparison of
      specific QOL instruments is lacking. We compared the psychometric properties of
      two QOL measures in parallel samples of mentally disturbed and non-patient
      subjects. We simultaneously administered the Quality of Life Enjoyment and
      Satisfaction Questionnaire (Q-LES-Q) and self-report items of the Lancashire
      Quality of Life Profile (LQOLP) to 199 patients with severe mental disorders and
      175 non-patients. The patients were evaluated with psychiatric rating scales. We
      identified five concordant domains, and five instrument-specific domains for the
      LQOLP and four for the Q-LES-Q. The Q-LES-Q provides better psychometric
      properties than the LQOLP in both samples. Both instruments show a good capacity
      to evaluate QOL and discriminate between the patients and non-patient controls.
      Within the patient sample, both QOL measures showed similarly negative
      correlations with severity of depression, but not mania, positive, negative, and
      general symptomatology. Both instruments proved to be mental health related, but
      neither was mental-disorder specific. Despite the acceptable psychometric
      properties and correlation of general QOL indices, similar QOL domains proved to
      be instrument specific and not sufficiently compatible. These discrepancies
      should be considered when comparing evaluations from similar domains in these QOL
      scales.

PMID- 12206578
TI  - Reliability and validity of the child health questionnaire-child form (CHQ-CF87)
      in a Dutch adolescent population.
AB  - Feasibility, reliability, and discriminative validity of the cross-culturally
      adapted Dutch version of the originally US child health questionnaire-child form
      (CHQ-CF87), an 87-item generic pediatric health-related quality of life
      instrument, were assessed. The success criterion in this first evaluation was the
      equivalence of psychometric properties of the adapted and the original CHQ. A
      total of 466 schoolchildren (9-17 years) were invited to complete the
      questionnaire in the classroom. Test-retest reliability was measured after 14
      days in a subgroup (n = 71). Response was 96%. Four scales had ceiling effects
      (>50%), as was reported in an Australian study. Cronbach alpha-values were
      adequate (>0.70), except for 'physical functioning' (0.56). Test-retest
      correlations, not previously reported, were not statistically significant for two
      CHQ-scales, whereas average retest scores indicated better health for five scales
      (p < 0.01). The CHQ scales discriminated significantly (p < 0.01) between
      children without (n = 281) and children with two or more self-reported chronic
      diseases (n = 59). This is in correspondence with US and Australian reports.
      CONCLUSIONS: The current data support application of the Dutch CHQ-CF in
      predominantly healthy populations, e.g. in school settings. Given the limitations
      of this study and some less favorable results (score distributions, internal
      consistency, test-retest reliability), further evaluation of the CHQ-CF is
      recommended, preferably by analyses of item performance and scale validity in
      international data sets that include varied clinical subgroups.

PMID- 12206577
TI  - Psychometric validation of an overactive bladder symptom and health-related
      quality of life questionnaire: the OAB-q.
AB  - OBJECTIVE: Overactive bladder (OAB) is characterized by symptoms of urinary
      frequency and urgency, with and without incontinence, and has been shown to have
      significant impact on health-related quality of life (HRQL). Currently, no OAB
      specific questionnaires exist to evaluate all symptoms of OAB; thus we sought to
      evaluate the psychometric properties of a newly developed OAB HRQL questionnaire.
      METHODS: The 33-item, self-administered OAB-q contains a symptom bother and HRQL
      scale. Both the OAB-q and SF-36 were completed by participants from two sources:
      (1) a community sample who screened positive for OAB in a random-digit dial
      telephone survey and participated in a clinical validation study (n = 254); and
      (2) a clinical study of patients' seeking treatment for OAB symptoms (baseline
      assessment) (n = 736). Item and exploratory factor analysis were performed to
      assess the subscale structure of the questionnaire. Psychometric evaluation was
      conducted to assess reliability and validity. RESULTS: Seventy-four percent of
      the sample were women with mean age of 58.5. Participants with continent and
      incontinent symptoms reported significantly greater symptom bother and HRQL
      impact than normal participants. Significant differences were present among all
      patient groups in all OAB-q subscales (p < 0.0001) except sleep where the impact
      of continent and incontinent OAB was similar, but significantly worse than normal
      participants (p < 0.0001). Internal consistency was high with the subscale
      Cronbach alpha-values ranging from 0.86 to 0.94. CONCLUSION: The OAB-q is a
      reliable and valid instrument that discriminates between normal and clinically
      diagnosed continent and incontinent OAB participants. The OAB-q demonstrates that
      both continent and incontinent OAB symptoms cause significant symptom bother and
      have a negative impact on HRQL.

PMID- 12206579
TI  - The Psychosocial Impact of Assistive Devices Scale (PIADS): translation and
      preliminary psychometric evaluation of a Canadian-French version.
AB  - This article reports on the Canadian-French translation of the Psychosocial
      Impact of Assistive Devices Scale (PIADS), a 26-item questionnaire that measures
      the quality of life (QoL) impacts of using assistive technologies from the person
      with disability's point of view. Following standard procedures, the study
      included forward and backward translations, committee reviewing, pre-testing with
      bilingual lay people, and psychometric evaluation of the translated questionnaire
      with subjects with mobility impairment (n = 83) and visual impairment (n = 37).
      The use of translators translating in their mother tongue and the participation
      of one author of the questionnaire contributed to the quality of the translation.
      We found that words that had equivalence in English and French did not
      necessarily cover the same areas of meaning. The subscales (n = 3) and total
      scale of the French PIADS achieved good test-retest stability (ICC of 0.77-0.90)
      and internal consistency (0.75-0.94). Concurrent validity with the source PIADS
      also produced acceptable coefficients (0.77-0.83). At the item level, non
      significant t test (p > 0.10) results supported the premise that the scores were
      not different across languages, except for two items. The results are robust
      enough to recommend the use of the Canadian-French questionnaire for the
      investigation of the QoL impacts of assistive technologies for persons with
      disability.

PMID- 12206580
TI  - Development of the Korean versions of WHO Quality of Life scale and WHOQOL-BREF.
AB  - The purpose of this study was to develop the Korean version of World Health
      Organization Quality of Life study assessment instrument (WHOQOL) and WHOQOL
      BREF, an abbreviated version of WHOQOL and to identify contributing factors in
      the quality of life of Koreans. The WHOQOL and WHOQOL-BREF were translated into
      colloquial Korean according to instructions of the WHOQOL study group. Then the
      Korean questionnaire was applied to 538 subjects, composed of 171 medical
      patients and 367 healthy subjects who volunteered to rate the scale. Finally, 486
      subjects completed the rating. Collected data were analyzed statistically. The
      Korean version of WHOQOL and WHOQOL-BREF domain scores demonstrated good test
      retest reliability, internal consistency, criterion validity, content validity
      and discriminant validity. The physical, psychological, social and environmental
      domains made a significant contribution to explaining the variance in the quality
      of life while the independence and spiritual domains made a lesser contribution.
      The domain scores produced by the WHOQOL-BREF correlated highly with the WHOQOL.
      The physical health domain contributed most in overall quality of life, while the
      social domain made the least contribution. These results suggest that the Korean
      version of WHOQOL and WHOQOL-BREF are valid and reliable in the assessment of
      quality of life and that physical domain is contributing most and social and
      spiritual factors are contributing least to the quality of life in Koreans.

PMID- 12206581
TI  - Validation assessment of the Chinese version of the Snore Outcomes Survey.
AB  - The aim of this study was to use a parallel model to translate the Snore Outcomes
      Survey (SOS) into Mandarin Chinese language by comparing performing
      characteristics and statistical properties of the original and Chinese versions
      SOS. The Chinese version SOS (CSOS) was validated in a prospective, non
      randomized manner. A total of 359 patients with sleep-disordered breathing (SDB)
      aged 18 years and older diagnosed as having SDB participated in the study at
      entry. Reliability, validity, and longitudinal sensitivity data for CSOS were
      obtained. CSOS demonstrated good test-retest reliability (Intra-class correlation
      coefficient = 0.751). The Cronbach's alpha coefficient was 0.86. The item-total
      correlation coefficients varied from 0.30 to 0.99. The CSOS correlated well with
      polysomnogram (PSG) parameters including respiratory distress index (RDI), lowest
      arterial O2 saturation (LAST). CSOS also yielded significant correlations with
      vitality subscale of Chinese Taiwan version SF-36 (r = 0.4, p = 0.0011). The
      standard response mean (SRM) for CSOS was 1.33. The validation demonstrated only
      minor effects of language; the statistical properties of the CSOS were equivalent
      to the English version. The CSOS is a valid tool to evaluate adults with SDB
      among Chinese-speaking population.

PMID- 12206582
TI  - The pest status and distribution of three cryptic blue oat mite species
      (Penthaleus spp.) and redlegged earth mite (Halotydeus destructor) in
      southeastern Australia.
AB  - Earth mites are pests of crops and pastures in southeastern Australia. Recent
      studies show differences between earth mite species in their mode of
      reproduction, preferred hosts and pesticide tolerance. This paper examines the
      distribution and pest status of each species. The southeastern Australian
      distribution for each species is mapped, incorporating new data from eastern New
      South Wales, South Australia and Tasmania. A new population of an undescribed
      species previously identified from northwestern Victoria was found in northern
      New South Wales. CLIMEX was used to identify climatic factors limiting the
      distribution of P. major and P. falcatus, the most broadly distributed species.
      This analysis suggests tolerance to heat and desiccation limits the inland
      distribution of these two species. A three-year survey of agricultural outbreaks
      indicates that all Penthaleus species are major agricultural pests although their
      pest status on crop types appears to differ. All species contributed to chemical
      control failures. However P. falcatus, previously identified in laboratory tests
      as having increased tolerance to pesticides, was the most common species
      associated with control failures. A laboratory experiment indicated that mites
      are sometimes pests on crops on which they cannot persist for a generation.
      Results are discussed with respect to management of these agricultural pests.

PMID- 12206583
TI  - Resistance to 2-tridecanone in Tetranychus urticae: effects of induced
      resistance, cross-resistance and heritability.
AB  - Earlier studies of resistance to the tomato toxin 2-tridecanone revealed similar
      levels of resistance among tomato and cucumber strains of Tetranychus urticae,
      whereas we anticipated the tomato strains to have a higher resistance. Between
      strain differences, however, may be concealed by toxin accumulation and/or cross
      resistance. Mites do accumulate 2-tridecanone to a considerable extent, but we
      have shown before that this cannot explain the lack of difference in resistance.
      In this paper, we provide evidence against cross-resistance: selection for
      resistance to a homologous compound from cucumber, 2-nonanone, did not confer
      resistance to 2-tridecanone. Observed increases in resistance levels over
      generations may be due to induction or selection. To study induction, adult
      females from a cucumber strain and a tomato strain were exposed to a sublethal
      dose of 2-tridecanone. One day after exposure, the cucumber strain gained in
      resistance to 2-tridecanone (c. 8-fold), whereas the tomato strain showed a
      decrease in resistance. These changes in resistance disappeared within three days
      after exposure, the time the mites need to dispose themselves of the toxin. The
      results support earlier findings that resistance is induced in the cucumber
      strain, but not in the tomato strain. To assess the heritability of resistance to
      2-tridecanone, offspring was obtained from individual females, and both the
      mothers and their offspring were tested for resistance. For the cucumber strain,
      offspring from susceptible or resistant mothers did not differ in resistance. For
      the tomato strain, however, offspring from resistant mothers were significantly
      more resistant to the toxin than offspring from susceptible mothers. This result
      provides unambiguous evidence that resistance to 2-tridecanone can be selected
      for.

PMID- 12206584
TI  - Population dynamics of interacting predatory mites, Phytoseiulus persimilis and
      Neoseiulus californicus, held on detached bean leaves.
AB  - The success of combined release of the predatory mites Phytoseiulus persimilis
      and Neoseiulus californicus in suppression of spider mites may be related to the
      effects of the interactions between the two predators on their population
      dynamics. We studied population growth and persistence of the specialist P
      persimilis and the generalist N. californicus reared singly versus reared in
      combination after simultaneous and successive predator introductions on detached
      bean leaf arenas with abundant prey, Tetranychus urticae. and with diminishing
      prey. When reared singly with abundant prey, either predator population persisted
      at high densities to the end of the experiment. In every predator combination
      system with abundant prey and various initial predator:predator ratios N.
      californicus displaced P persimilis. When held singly with diminishing prey, the
      population of P. persimilis grew initially faster than the population of N.
      californicus but both species reached similar population peaks. Irrespective
      whether reared singly or in combination. N. californicus persisted three to five
      times longer after prey depletion than did P. persimilis. Regarding the crucial
      interactions in the predator combination systems, we conclude that intraguild
      predation was a stronger force than food competition and finally resulted in the
      displacement of P. persimilis. Previous studies showed that intraguild predation
      between the specialist P. persimilis and the generalist N. californicus is
      strongly asymmetric favoring the generalist. We discuss the implications of
      potential interactions between P. persimilis and N. californicus to biological
      control of spider mites.

PMID- 12206585
TI  - The natural control of the tracheal mite of honey bees.
AB  - The natural control of the tracheal mite, Acarapis woodi, of the honey bee
      depends greatly on good foraging opportunities for bee colonies and on limited
      competition between colonies. The severe, widely-publicised disease of bees,
      referred to as 'the Isle of Wight disease' in Britain early in the last century
      when colonies were more numerous than subsequently, was wrongly attributed to the
      mite, which causes no overt symptoms. The disease was almost certainly caused by
      bee paralysis virus, which does cause the symptoms and is independent of the
      mite, and which is similarly associated with large densities of bee colonies.

PMID- 12206586
TI  - Life-cycle of Suidasia medanensis (=pontifica) (Acari: Suidasiidae) under
      laboratory conditions in a tropical environment.
AB  - The life cycle of Suidasia medanensis (=pontifica) was studied under laboratory
      conditions at 26 degrees C and 86% relative humidity. Freshly laid eggs were
      observed until they developed into adults and the periods between stages were
      recorded. Production of eggs by mated females was monitored until they died. The
      eggs required an average of 12.6 +/- 0.6 days to develop into adults. Mean
      longevity of mated females and males was similar (48.6 +/- 13 and 49.1 +/- 20
      days, respectively). The conditions used in this study may be considered optimal
      for in vitro culture of S. medanensis.

PMID- 12206587
TI  - Abnormal development of Rhipicephalus sanguineus (Ixodidae).
AB  - Three malformed Rhipicephalus sanguineus specimens were noticed in a tick
      laboratory colony. These specimens had different degrees of twining, from an
      almost fused individual (with two anal pores) to a partially fused adult male,
      with four spiracular plates. One female was a heart-shaped specimen. with both
      body halves fused along a longitudinal axes, with four spiracular plates and two
      anal pores.

PMID- 12206588
TI  - The curve of Spee and craniofacial morphology: a multiple regression analysis.
AB  - The aim of this study was to investigate the relationship between the curve of
      Spee and skeletal facial morphology. Dental casts and lateral cephalograms were
      obtained from 59 orthodontic patients. The amount of concavity of the curve of
      Spee was calculated by a second-order quadratic interpolation of buccal cusp tips
      obtained from lateral digital photographs of the teeth. The cephalometric
      analysis aimed to evaluate the sagittal and vertical craniofacial dimensions as
      well as the position of the mandibular condyle with respect to the occlusal
      plane. These variables, included in a multiple regression model, could explain
      34% of the total variance of the curve of Spee. The amount of the curvature was
      significantly related to (a) the horizontal position of the condyle with respect
      to the dentition, (b) the sagittal position of the mandible with respect to the
      anterior cranial base, and (c) the ratio between the posterior and anterior
      facial height. No significant relationship was found between the curve of Spec
      and any of the other cephalometric variables. The curve of Spee was not
      influenced by age and gender of the subjects investigated.

PMID- 12206589
TI  - Detection of marginal defects of composite restorations with conventional and
      digital radiographs.
AB  - The purpose of this study was to determine the validity of detecting approximal
      imperfections of composite fillings using three intraoral radiographic systems in
      vitro. Class II composite resin restorations (108) with three radiopacities (264,
      306, 443% Al 99.5) of which 27 had marginal openings or overhangs, respectively,
      were conventionally (Ektaspeed plus) and digitally (Dexis, Digora) radiographed.
      Images were assessed by 10 observers for the presence of marginal gaps and
      overhangs, as well as for their need of restorative treatment according to a five
      point confidence rating scale. The validity of the observations were expressed as
      areas under receiver operating characteristic (ROC) curves (Aroc). Repeated
      measures analysis of variance revealed significant effects of 'radiographic
      system' and 'diagnostic purpose'. Marginal overhangs (Aroc = 0.90) were
      significantly easier to diagnose than openings (Aroc = 0.63). Marginal gaps were
      better detected on conventional and Dexis radiographs than on Digora images. the
      range of sensitivities and specificities of the treatment decision was 0.53-0.56
      and 0.87-0.88, respectively. It was concluded that the validity of detecting
      marginal defects of composite resin restorations based on radiographs was only
      slightly affected by the radiographic system being used. The diagnosis of
      marginal gaps frequently resulted in false-positive and false-negative decisions.

PMID- 12206590
TI  - A 3-year comparison of dental anxiety treatment outcomes: hypnosis, group therapy
      and individual desensitization vs. no specialist treatment.
AB  - Outcomes of hypnotherapy (HT), group therapy (GT) and individual systematic
      desensitization (SD) on extreme dental anxiety in adults aged 19-65 yr were
      compared by regular attendance behaviors, changes in dental anxiety and changes
      in beliefs about dentists and treatment after 3 yr. Treatment groups were
      comparable with a static reference control group of 65 anxious patients (Dental
      Anxiety Scale > or = 15) who were followed for a mean of nearly 6 yr. After 3 yr,
      54.5% of HT patients, 69.6% of GT patients and 65.5% of SD patients were
      maintaining regular dental care habits. This was better than the 46.1% of the
      reference group, who reported going regularly to the dentist again within the
      cohort follow-up period, and 38.9% of a control subgroup with observation for 3
      yr. Women were better regular attenders than men at 3 yr. Specialist-treated
      regular attenders were significantly less anxious and had more positive beliefs
      than regular attenders from reference groups. There were few differences between
      HT, GT and SD after 3 yr. It was concluded that many patients can, on their own,
      successfully start and maintain regular dental treatment habits with dentists
      despite years of avoidance associated with phobic or extreme anxiety. However, it
      also appears that these patients had less success in reducing dental anxiety and
      improving beliefs about dentists long-term than did patients who were treated at
      the specialist clinic with psychological strategies.

PMID- 12206591
TI  - Amine fluoride gel affects the viability and the generation of superoxide anions
      in human polymorphonuclear leukocytes: an in vitro study.
AB  - Amine hydrofluorides are widely used to prevent caries. As an acidulated gel,
      they were also studied for their applicability to reduce pathogenic bacteria in
      periodontal pockets. We assessed the toxicity of this pharmaceutical amine
      hydrofluoride preparation on human polymorphonuclear leukocytes in vitro by
      measuring Trypan blue exclusion and the generation of superoxide anions (O2) by
      the chemotactic peptide N-formyl-L-methionyl-L-leucyl-L-phenylalanine (fMLP)
      after a 3-min contact with gel. Depending on the experimental conditions, gel
      dilutions up to 1.3 x 10(4) resulted in an increase in Trypan blue-colored cells
      and liberation of beta-glucuronidase. Dilutions between 3 x 10(4) and 1 x 10(5)
      augmented the fMLP-mediated O2- generation, which could be prevented by Ca2+
      chelation with BAPTA-AM (1,2'-bis (o-aminophenoxyethane-N.N.N'.N'-tetraacetic
      acid tetra (acetoxymethyl) ester) and ethyleneglycoltetraacetic acid (EGTA) or
      inhibition of protein kinase C (PKC) with staurosporine and bisindolylmaleimide
      I. respectively. Compared with data published on the minimal inhibitory
      concentration for periodontal pathogenic bacteria, the cytotoxicity of amine
      hydrofluorides on eukaryotic cells is much greater and thus of consequence for
      their clinical use.

PMID- 12206592
TI  - Signal pathways involved in the production of MMP-1 and MMP-3 in human gingival
      fibroblasts.
AB  - Periodontitis is associated with enhanced production of cytokines, prostaglandins
      and matrix metalloproteinases (MMPs). The aim of this study was to investigate
      the production and regulation of MMP-1 and MMP-3 in human gingival fibroblasts
      challenged with the cytokines interleukin-lbeta (IL-1beta), tumor necrosis factor
      alpha (TNFalpha) or epidermal growth factor (EGF). The results showed that
      gingival fibroblasts constitutively produce MMP-1 and MMP-3, and that the
      cytokines IL-1beta, TNFalpha and EGF increase both MMP-1 and MMP-3 production in
      gingival fibroblasts. The upregulation by the cytokines was apparent at 8 h of
      incubation and increased thereafter continuously during 48 h of incubation. The
      upregulation of MMPs, induced by IL-1beta or TNFalpha, was reduced by the
      cyxlooxygenase-2 (COX-2) inhibitor NS-398, the p38 MAP-kinase inhibitor SB
      203580, and the tyrosine kinase inhibitor herbimycin A. In addition, MMP-1 and
      MMP-3 production, induced by IL-1beta, TNFalpha or EGF, was strongly reduced by
      the presence of the glucocorticoid dexamethasone. Our findings demonstrate that
      the cytokines IL-1beta, TNFalpha and EGF, respectively, enhance both MMP-1 and
      MMP-3 production in human gingival fibroblasts, and that the signal pathways COX
      2, MAP-kinases and tyrosine kinases are partly involved in the production of
      MMPs.

PMID- 12206594
TI  - Expression of cytoskeletal proteins in developing human minor salivary glands.
AB  - The presence of an epithelium at different stages of proliferation and
      differentiation raises interesting questions concerning the histogenesis, cell
      turnover and differentiation of normal salivary glands. In order to expand
      knowledge of these aspects, we investigated the expression of cytokeratins (CKs)
      7,8,10,13,14,16,18 and 19, vimentin (VIM), and smooth muscle actin (SMA) in
      developing human minor salivary glands using monoclonal antibodies. Labial,
      buccal, palatine, and lingual salivary glands and those from the floor of the
      mouth were obtained from human fetuses (forensic postmortem) ranging in age from
      gestational weeks 10 to 29. Serial sections, 3 microm thick, were immunostained
      using a strepto-avidin-biotin technique. Reactivity for all antibodies was
      negative in the salivary gland epithelium during the developmental stages of bud
      formation, cord growth, and branching of cord. During canalization and
      cytodifferentiation, the glandular epithelial cells showed a positive reaction to
      some CKs and SMA. Cytokeratins 7, 8, 18, and 19 showed strong labeling in luminal
      duct cells that exhibited some degree of morphological differentiation.
      Myoepithelial cellc were recognized by antibodies to SMA. Cytoskeletal protein
      expression changes according to the cell type, degree of differentiation, and
      stage of morphological development of the glandular structure. These changes
      occur independently of the localization of the gland.

PMID- 12206593
TI  - Enamelysin and kallikrein-4 mRNA expression in developing mouse molars.
AB  - Proteolytic processing and degradation of enamel matrix proteins appears to be an
      essential feature of dental enamel formation. The source and character of
      proteolytic activity in the enamel matrix of developing teeth changes as enamel
      formation progresses. Two proteinases have been isolated from the extracellular
      enamel matrix of developing teeth: enamelysin (MMP-20), a matrix
      metalloproteinase. and kallikrein-4 (KLK4), a serine proteinase. Here, we ask if
      the expression of MMP-20 and KLK4 correlate with the stage-associated changes in
      the digestion of enamel proteins. Using in situ hybridization, we localized MMP
      20 and KLK4 mRNA in mouse maxillary first molars on postnatal days 1, 2, 3, 5, 6,
      7, 9, 11, and 14. Enamelysin signal was first detected in preameloblasts,
      ameloblasts, and odontoblasts on day 2, but not in ameloblasts covering the
      enamel-free zone. Enamelysin signal declined in ameloblasts on day 6 but
      persisted in the dental pulp. In contrast, KLK4 transcripts were first observed
      on day 3 in pulp and on day 6 in ameloblasts covering the enamel-free zone. the
      KLK4 signal was present in maturation-stage ameloblasts on days 9, 11, and 14.
      The expression patterns of MMP-20 and KLK4 by ameloblasts in mouse molars are
      stage-specific and complementary.

PMID- 12206595
TI  - Micro-tensile bond strength of two adhesives to Erbium:YAG-lased vs. bur-cut
      enamel and dentin.
AB  - The purpose of the study was to assess the hypotheses that laser irradiation is
      equally effective for bonding as traditional acid-etch procedures, and that tooth
      substrate prepared either by Erbium:YAG laser or diamond bur is equally receptive
      to adhesive procedures. Buccal/oral enamel and mid-coronal dentin were laser
      irradiated using an Erbium:YAG laser. A total-etch adhesive (OptiBond FL) applied
      with and without prior acid-etching and a self-etch adhesive (Clearfil SE Bond)
      were employed to bond the composite. The micro-tensile bond strength (microTBS)
      was determined after 24 h of storage in water. Failure patterns were analysed
      using a stereo-microscope, and samples were processed for Field-emission Scanning
      Electron Microscopy (Fe-SEM) evaluation. Unbonded, lased enamel and dentin
      surfaces were evaluated using Fe-SEM as well. The total-etch adhesive bonded
      significantly less effectively to lased than to bur-cut enamel/dentin. Laser
      'conditioning' was clearly less effective than acid-etching. Moreover, acid
      etching lased enamel and dentin significantly improved the microTBS of OptiBond
      FL. The self-etch adhesive performed equally to lased as to bur-cut enamel, but
      significantly less effectively to lased than to bur-cut dentin. It is concluded
      that cavities prepared by laser appear less receptive to adhesive procedures than
      conventional bur-cut cavities.

PMID- 12206596
TI  - Effects of aging and cyclic loading on the mechanical properties of glass ionomer
      cements.
AB  - The purpose of this study was to examine the effect of cyclic loading on the
      flexural strength and fracture toughness of a conventional glass ionomer cement
      (GIC), a metal containing GIC, hybrid GICs, and, for comparison, a composite. Two
      sets of specimens were evaluated: a set of controls (at 37 degrees C and 95%
      humidity) and a set aged for 9 months at 37 degrees C in water. The specimens
      were tested in static loading in air and water, and cyclic loaded in water.
      Cyclic loading and aging decreased the flexure strength of all materials
      significantly. However, wet static fracture toughness did not change on aging,
      and occasionally increased. Cyclic fracture toughness was lower with all
      materials except a hybrid glass ionomer without aging. Deterioration in
      properties was related to relative amount of glass ionomer vs. the resin
      component. Both flexural strength and fracture toughness of these materials were
      significantly affected by testing environment, aging and cyclic loading. The
      lower the resin component of the material, the lower the mechanical properties.
      The influence of these parameters should be given importance in considering their
      clinically durability in the oral environment.

PMID- 12206597
TI  - Obturator bypass: a classic approach for the treatment of contemporary groin
      infection.
AB  - As the number of cardiac and interventional radiologic procedures has risen, the
      frequency with which surgeons are called to treat groin complications has
      increased. Infectious groin problems that often involve foreign prosthetic
      material or remnants of percutaneous femoral closure devices are particularly
      challenging and require control of bleeding, removal of foreign material, wide
      debridement, and sometimes arterial resection. Management of the consequential
      limb ischemia in such cases is controversial. The purpose of this study is to
      review the utility of extra-anatomic common femoral bypass through the obturator
      foramen (obturator bypass) as a method of treating limb ischemia after arterial
      groin infection. From July 1992 through June 2001 a total of 12 patients (six
      male) presented with severe vascular infections of the groin and underwent
      obturator bypass. Infections occurred as a consequence of an isolated vascular
      graft infection (nine) or after a percutaneous interventional femoral access
      procedure (three). Patients presented with systemic sepsis and a draining sinus
      (six), infected pseudoaneurysm (two), or hemorrhage (four). Treatment included
      debridement of the groin wound, sartorius muscle flap coverage of the femoral
      vessels, antibiotics and synthetic (eight polytetrafluoroethylene and four
      Dacron) obturator bypass via a lower abdominal extraperitoneal incision from an
      aortobifemoral bypass graft limb to the superficial femoral artery (six), native
      iliac to femoral artery (three), iliac to popliteal artery (two), and
      aortobifemoral bypass limb to the popliteal artery (one). Graft patency and limb
      salvage were assessed by Kaplan-Meier life table analysis. There were two (17%)
      deaths (multisystem organ failure at postoperative days 9 and 6) and four major
      complications (25%) requiring reoperation in the first 30 days. Ten patients
      (83%) survived, healed their groin wounds, and are infection free. With a mean
      follow-up of 37 months graft patency and limb salvage at 60 months were 80 and 60
      per cent, respectively. There were no late graft infections. We conclude that the
      obturator bypass is an effective and durable means of revascularization in the
      presence of the septic groin. This procedure belongs in the armamentarium of all
      surgeons managing these complications.

PMID- 12206598
TI  - Surgical experience with functioning pancreatic neuroendocrine tumors.
AB  - Pancreatic islet-cell tumors (ICTs) are rare malignancies usually recognized by
      specific clinical endocrinopathies. The purpose of this study is to evaluate our
      surgical experience with functioning pancreatic ICT in an academic referral
      center. Twenty patients (male:female 12:8) with a mean age of 53 years (range 26
      82) underwent surgery for a functioning pancreatic ICT [gastrinoma (eight),
      multiple endocrine neoplasia (three), insulinoma (seven), glucagonoma (four), and
      VI-Poma (vasoactive intestinal peptide; one)] between June 1975 and March 2001.
      Signs and symptoms of hormonal excess were present in 95 per cent (19 of 20). One
      patient (glucagonoma) presented with obstructive jaundice and mild glucose
      intolerance. Elevated peptide levels were detected preoperatively in 65 per cent,
      including all patients with an insulinoma. Curative resections were attempted in
      80 per cent including three procedures for insulinoma. Palliative procedures were
      performed in 20 per cent--all gastrinomas. One patient with an insulinoma had
      diffuse nesidioblastosis. Three patients (with gastrinoma, insulinoma, and
      glucagonoma) had lymph node-positive disease and three patients with gastrinoma
      had liver metastasis. The overall 30-day morbidity rate was 30 per cent and
      mortality rate 0 per cent. Symptomatic improvement was achieved in 90 per cent at
      a mean follow-up of 44 months. Two patients developed diabetes after a subtotal
      and a total pancreatectomy, respectively. Sixty-three per cent of patients who
      underwent an attempted curative resection are alive at a mean follow-up of 47
      months (range 3-231) and all patients who underwent a palliative procedure are
      alive at a mean follow-up of 31 months (range 27-36). Functioning pancreatic ICTs
      are fascinating tumors that produce distinct clinical syndromes. Symptomatic
      improvement is accomplished in the majority of patients after surgery and short
      term palliation is achieved in patients with nonresectable disease.

PMID- 12206599
TI  - Cytoreductive surgery in patients with advanced-stage carcinoid tumors.
AB  - The role of aggressive surgical resections as well as criteria for resectability
      in patients with advanced carcinoid tumors is not clearly defined. Thirty
      patients (17 male and 13 female) who were previously diagnosed to have
      "unresectable carcinoid disease" were treated using a multimodality approach over
      a period of 2 years. Extensive liver involvement was present in 28 of 30 (93%) of
      the cases. Small bowel involvement was noted in 22 of 30 (73%), and
      peritoneal/retroperitoneal/mesenteric invasion was observed in 15 of 30 (50%) of
      the cases. Three patients had remote metastases (brain, bone, and eye). Twenty of
      30 (66%) patients had carcinoid syndrome with severely disabling symptoms. Eight
      patients (26%) had small bowel obstruction. All patients underwent at least one
      surgical exploration/intervention. Radiofrequency ablation (RFA) of one or more
      liver lesions was performed as an adjunct in 22 of 30 (73%) patients. Six
      patients (20%) had a second surgical procedure. There were 11 complications in
      eight patients (27%) after the initial operation. Median hospital stay for
      patients who underwent RFA only, RFA/liver resection, and liver resection with
      abdominal tumor debulking were 2, 4, 8, and 16 days respectively. Twenty-five of
      30 patients (83%) showed symptomatic improvement. Mean pre- and postoperative
      Karnofsky physical performance scores were 55 and 85 respectively (P < 0.02).
      Small bowel obstruction was due to adhesions in five patients. All patients with
      intestinal obstruction had complete relief of their symptoms postoperatively. 5
      Hydroxyindolacetic acid levels decreased by 50 per cent in all patients with
      follow-up determinations available. Aggressive surgical exploration and tumor
      debulking could be performed with significantly improved symptomatic outcome and
      relatively minor complications. Longer follow-up is needed for assessment of
      effect on survival.

PMID- 12206600
TI  - Surgical management of primary breast sarcoma.
AB  - Primary sarcoma constitutes less than one per cent of breast malignancies. A
      retrospective review of this disease at our institution was undertaken to assess
      the effect of different treatment modalities on outcome. Over a 24-year period 28
      patients were identified. Follow-up ranged from one to 228 months. Partial
      mastectomy was done in seven patients, whereas ten underwent total mastectomy and
      nine had modified radical mastectomy. Two refused surgery. All margins of
      resection were negative. In total ten axillary lymph node dissections were done
      with no positive nodes identified. Pathologic analysis of tumors revealed a
      variety of sarcomas including high-grade malignant cystosarcoma phyllodes in 13.
      Recurrence of disease occurred in two women, both with malignant cystosarcoma
      phyllodes. One was a local recurrence in a patient who had undergone partial
      mastectomy. This was successfully treated with a total mastectomy. The second
      recurrence involved a distant metastasis in a patient treated with modified
      radical mastectomy that eventually led to her death. For the entire group the
      disease-free survival was 75 per cent at 10 years whereas overall survival was
      87.5 per cent. In conclusion an adequate margin of resection is the single most
      important determinant of long-term survival. Axillary lymph node dissection is
      not necessary for the treatment of these tumors.

PMID- 12206601
TI  - A comparison of total thyroidectomy and lobectomy in the treatment of dominant
      thyroid nodules.
AB  - Patients with a clinically concerning dominant thyroid nodule have been managed
      by lobectomy or total thyroidectomy at our institution. We determined the
      complications associated with both approaches and the ability of thyroid
      lobectomy to avoid the need for thyroid hormone replacement therapy. Records of
      all patients with a dominant thyroid nodule managed with surgery from August 1993
      through December 2000 were reviewed for demographics, history of head and neck
      radiation, indication for surgery, preoperative fine-needle aspirate results,
      final pathologic evaluation, perioperative complications, determinations of need
      for subsequent thyroid surgery after lobectomy, and need for thyroid hormone
      replacement therapy after surgery. Patients with a preoperative diagnosis of
      malignancy or bilateral or diffuse disease were excluded because these conditions
      would uniformly be managed by bilateral thyroidectomy. The complications for the
      lobectomy group (n = 131) compared with the total thyroidectomy group (n = 84)
      were: recurrent laryngeal nerve paresis (4.6% vs 2.4%), recurrent laryngeal nerve
      injury (0.8% vs 0), and transient hypoparathyroidism (1.5% vs 9.5%; P = 0.007).
      No permanent hypoparathyroidism was identified in either group. Postoperative
      thyroid hormone replacement was required in 64 of 131 lobectomy patients (48.8%).
      Complications associated with either surgery were low. Total thyroidectomy was
      not associated with clinically significant additive morbidity. Patients treated
      by lobectomy should be aware of a nearly 50 per cent chance of requiring thyroid
      hormone replacement. Total thyroidectomy avoids future thyroid surgery; lobectomy
      patients remain at risk. When complications can be minimized total thyroidectomy
      should be considered an option in the management for patients with dominant
      thyroid nodules that require surgery.

PMID- 12206602
TI  - Sequential dermal-peritumoral radiocolloid injection for sentinel node biopsy for
      breast cancer: the University of Florida experience.
AB  - Although sentinel lymph node (SLN) biopsy is rapidly becoming the standard of
      care for small breast cancers the optimal radiocolloid injection technique
      remains controversial. We report our experience with sequential dermal
      peritumoral radiocolloid injection that takes advantage of both techniques. One
      hundred eighteen patients with clinical stage T(is), T1, T2 and N0 breast cancer
      underwent SLN biopsy at the University of Florida. Twelve to 18 hours before
      surgery patients received either an injection of 0.5 to 1.0 mCi 50:50
      filtered:unfiltered technetium sulfur colloid into the dermis overlying the tumor
      and/or a peritumoral injection of a 3 to 4-mCi of radiocolloid 30 minutes later.
      Dynamic lymphoscintigraphy was performed and the topographical location of all
      imaged lymph nodes was marked on the skin. The next morning the surgeon utilized
      a hand-held gamma probe to remove all SLN(s) defined as any lymph node with
      radioactive counts 10 per cent or more of the ex vivo counts of the most
      radioactive SLN [internal mammary (IM) nodes were not removed]. The SLN
      identification rate was 98.5 per cent (3 IM nodes) for dermal injection (d.),
      83.3 per cent (1 IM node) for peritumoral injection (p.), and 100 per cent (14 IM
      nodes) for sequential dermal-peritumoral injection (d.p.) (p < 0.05 DP versus D).
      Sequential d.p. 50:50 filtered:unfiltered technetium sulfur colloid injection
      results in a rapid, high SLN identification rate that persists until surgery the
      next morning. Delineation of nonaxillary SLNs may lead to more accurate breast
      cancer staging and may also influence the delivery of IM node radiation.

PMID- 12206603
TI  - Assessment of initial base deficit as a predictor of outcome: mechanism of injury
      does make a difference.
AB  - Initial base deficit in injured patients has been shown to predict the adequacy
      of resuscitation and outcome. The usefulness of base deficit as a predictor of
      outcome, however, may be dependent on the mechanism of injury. We conducted a
      retrospective review of the trauma registry, supplemented by chart review, of all
      trauma patients treated at a Level I trauma center from January 1995 through July
      2001. Data collected included mechanism of injury, base deficit, Injury Severity
      Score, and outcome. From 1995 through 2001 a total of 3275 patients (23% of
      trauma admissions) at a mean age of 34 +/- 15 years had a base deficit recorded
      at the time of admission. The patients were 78 per cent male, and the mechanism
      of injury was blunt trauma in 58.2 per cent. Mortality increased with successive
      increases in base deficit but was markedly lower for a given base deficit in
      those patients having sustained stab wounds and/or severe lacerations as compared
      with those with gunshot wounds or blunt trauma. The value of the base deficit as
      a predictor of outcome depends upon the mechanism of injury and appears most
      useful for patients sustaining gunshot wounds or blunt trauma. Future studies in
      patients with penetrating trauma using base deficit as a predictor of outcome
      should separate patients with gunshot wounds from those with stab wounds or
      lacerations.

PMID- 12206604
TI  - Cryosurgery of close or positive margins after hepatic resection for primary and
      metastatic hepatobiliary malignancies.
AB  - Obtaining a one-centimeter negative margin is an important factor in preventing
      disease recurrence after surgery for hepatic tumors. Cryotherapy of the resected
      edge has been used to achieve optimal margin clearance in cases in which the
      alternative would be an extended high-risk liver resection. The effect of this
      technique on margin recurrence was examined. Between 1994 and 2001 a total of 56
      patients underwent cryosurgery with or without resection for primary and
      metastatic hepatobiliary malignancies. A 5-cm cryotherapy lollipop probe was used
      to ablate surgical margins less than one centimeter in 13 of these patients.
      There were seven colorectal metastases, three hepatocellular carcinomas, and
      three gallbladder carcinomas. The median size of the colorectal and
      hepatocellular lesions was 3 cm (range 2-14 cm), and all gallbladder primaries
      were T2 tumors. All tumors except three were located centrally in the liver
      requiring cryoablation of margins at segments 4, 5, and 8. Most patients had one
      site frozen (n = 9) with a median target temperature of -190 degrees C and a
      median of two freeze-thaw cycles. Final pathological analysis of the resected
      specimens revealed nine close (<1 cm) and four positive margins. With a median
      follow-up of 16 months seven patients are alive with no evidence of disease and
      six have developed recurrences with three of them dying of their disease. Only
      one (8%) of the initial recurrences was at the cryoablated margin. Cryosurgery of
      the resection edge facilitates liver resection for malignant tumors when margins
      are close or positive. Because disease recurrence at the cryoablated margin is
      low this technique may allow more patients to undergo effective surgical
      treatment of their hepatobiliary cancers.

PMID- 12206605
TI  - Efficacy of computed tomography in the diagnosis of pancreatic injury in adult
      blunt trauma patients: a single-institutional study.
AB  - Blunt trauma to the pancreas is an uncommon injury, which can be difficult to
      diagnose. Most studies are multi-institutional, include both helical and axial
      CT, and report sensitivities of 40 to 67 per cent. We evaluated the efficacy of
      spiral CT for the diagnosis of blunt pancreatic injury in a single large-volume
      institution. We retrospectively reviewed 22,000 blunt trauma patients seen
      between 1996 and 2000. Pancreatic injury was identified in 40 patients (0.2%).
      All patients evaluated with spiral CT were given both oral and intravenous
      contrast. A total of 40 blunt pancreatic injuries were identified. The mean age
      was 35 years. Seventy-five per cent were male. Mean Injury Severity Scale score
      was 29 and overall mortality 12.5 per cent. Thirty-one patients (78%) underwent
      laparotomy. Twelve patients went directly to the operating room for urgent
      exploration and 19 had a preoperative CT. CT was positive for pancreatic injury
      in 13 patients (sensitivity 68%). All 13 patients had confirmed pancreatic injury
      at the time of surgery (positive predictive value = 100%). Using the American
      Association for the Surgery of Trauma grading system operative findings and CT
      correlated in 68 per cent of those patients who had both CT and laparotomy. CT
      underestimated pancreatic injury in the remaining 31 per cent. Nine patients were
      managed nonoperatively without complication, and six had pancreatic injury on CT.
      The other three had a negative CT but had clinical and laboratory evidence of
      pancreatic injury. Overall CT scan was 68 per cent (19 of 28) accurate in
      diagnosing pancreatic injury. We conclude that CT scan is only moderately
      sensitive and can underestimate or miss pancreatic injury. Although CT moderately
      correlated with injury grade it was highly predictive for presence of injury. The
      new multidetector helical scanner may improve our diagnostic ability.

PMID- 12206606
TI  - Management of Fournier's gangrene: an eleven year retrospective analysis of early
      recognition, diagnosis, and treatment.
AB  - Fournier's gangrene is an infectious necrotizing fasciitis of the perineum and
      genital regions. It is a synergistic infection caused by a mixture of aerobic and
      anaerobic organisms. The mortality rate from this infection ranges from 0 to 67
      per cent. One of the most important determinants of overall outcome is early
      recognition and extensive surgical debridement upon initial diagnosis. This is
      followed by aggressive antibiotic therapy combined with other precautionary and
      resuscitative measures. Our hypothesis is that early aggressive surgical
      debridement combined with broad-spectrum antibiotic coverage results in decreased
      mortality from Fournier gangrene. The objective of this study was to determine
      our morbidity and mortality as compared with other institutions. This was a
      retrospective review of 200 charts of patients from 1990 through 2001. The charts
      reviewed included patients with a diagnosis of male and female genital abscesses,
      cellulitis, necrotizing fasciitis, and vascular disorders. This resulted in 33
      patients who had a final diagnosis of Fournier's gangrene. There were 26 (79%)
      males and seven (21%) females with a diagnosis of Fournier's gangrene. The
      patients ranged in age from 30 to 85 years (mean age 51.5). There were a number
      of predisposing factors that were examined. Thirteen patients (39%) were
      diabetic, 18 (55%) suffered from hypertension, 18 (55%) were obese, and 18 (55%)
      were cigarette smokers. Four patients (12%) had no predisposing factors. The
      treatment consisted of wide surgical debridement which was performed in all 33
      patients. Most patients received multiple debridements ranging from one surgery
      to seven (mean 3.25) per hospital stay. The majority of patients received broad
      spectrum antibiotic coverage. Three patients died, which resulted in a mortality
      rate of 9 per cent. Early recognition and aggressive surgical debridement is the
      most essential intervention in stopping the rapidly progressing infectious
      process of Fournier's gangrene. This intervention should be combined with
      aggressive triple-antibiotic therapy and other precautionary measures for
      supporting the patient who has the systemic effects of Fournier's gangrene. Our
      data do not reach statistical significance with regard to the use of triple
      antibiotic therapy. However, we believe that it is an important part of the
      treatment regimen. The combination of aggressive surgical therapy and appropriate
      antibiotic coverage results in a reduction in mortality.

PMID- 12206607
TI  - Diagnosis and management of enterovesical fistulas in patients with Crohn's
      disease.
AB  - The objective of this study was to investigate the clinical manifestations and
      diagnostic studies used to evaluate Crohn's patients with enterovesical fistulas
      (EVFs) and to assess outcome after surgical intervention. This is a ten year
      multi-institutional retrospective chart review of patients with Crohn's disease.
      Of 400 patients identified with Crohn's disease eight (2%) were diagnosed with
      EVF. The mean age at diagnosis was 27 years. No patients had prior surgeries for
      Crohn's. Duration of symptoms ranged from 6 months to 15 years. There were seven
      ileovesical and one colovesical fistula identified. One patient had associated
      perianal disease. Three had concomitant enteroenteral fistulae. Clinical features
      included pneumaturia in seven patients (88%), fecaluria in three (38%), hematuria
      in five (63%), and urinary tract infection symptoms in seven (88%). Diagnostic
      studies included CT scan in six, barium or gastrografin enema in four, and
      cystoscopy in four. Surgical therapy involved resection of the affected bowel.
      The bladder defect was closed primarily in two layers in all patients using
      absorbable suture, with omental patch in four. Two patients underwent ileostomy
      and one underwent colostomy, all taken down within 6 months. There were no
      bladder leaks and no anastamotic leaks. There were no perioperative deaths. The
      mean postoperative stay was nine days. The mean follow-up was 39 months. We
      conclude that pneumaturia is a strong clinical indicator of EVF. CT has been
      valuable in identifying gas within the bladder in these patients. Cystoscopy has
      proven useful in identifying the fistulous tract and in evaluation of the
      ureters. The presence of an EVF should heighten suspicion as to the presence of
      concomitant enteroenteral fistulae. Barium or gastrografin studies are useful in
      this capacity. Surgical treatment of EVFs should include resection of affected
      bowel. The bladder defect can safely be closed using absorbable suture.

PMID- 12206608
TI  - Resection of benign esophageal stricture through a minimally invasive endoscopic
      and transgastric approach.
AB  - Recurrent benign esophageal strictures that are refractory to dilation can be
      difficult to manage. We report a novel technique for treatment of a recurrent
      esophageal stricture using a minimally invasive endoscopic and transgastric
      approach. The patient is a 40-year-old women who developed a recurrent distal
      esophageal stricture after repair of an esophageal perforation. Multiple prior
      dilations had been unsuccessful in achieving sustained esophageal patency, and
      the patient presented with a complete distal obstruction demonstrated on barium
      esophagram. Two flexible endoscopes were used: one placed through the mouth and
      another through a gastrostomy. While the transilluminated lesion was visualized
      from below the obstruction was traversed with an endoscopic aspiration needle
      from above. A guidewire was placed through the needle and pulled out the
      gastrostomy. Both the esophageal lesion and the gastrostomy tract were then
      serially dilated over the wire. After dilation the residual stricture was
      resected using a circular stapler placed through the dilated gastrostomy tract.
      After this procedure the patient maintained esophageal patency with a diminished
      need for dilation. Details of our technique are described and the literature is
      reviewed.

PMID- 12206609
TI  - Unusual presentations of gastroschisis.
AB  - Gastroschisis is a defect of the ventral abdominal wall nearly always located to
      the right of the umbilicus. A relatively low incidence of associated anomalies
      exists with the most common being nonduodenal intestinal atresia occurring in 10
      per cent of patients. Although multiple hypotheses have been proposed the
      pathogenesis of gastroschisis is unproven and controversial. Herein we describe
      four infants with rare presentations of gastroschisis: one infant with true left
      sided gastroschisis and three infants with unusual patterns of intestinal
      atresia. At present there is a female preponderance of left-sided gastroschisis
      as reported in the world literature (five female:two male). These cases
      illustrate the anatomic spectrum of gastroschisis as well as support intrauterine
      spontaneous closure of the abdominal wall defect as an etiology for midgut
      atresia.

PMID- 12206610
TI  - Fibrin sealant facilitates hemostasis in arteriovenous polytetrafluoroethylene
      grafts for renal dialysis access.
AB  - A prospective randomized study was performed to evaluate the efficacy of fibrin
      sealant (FS) in patients undergoing upper-extremity polytetrafluoroethylene
      (PTFE) graft placement for dialysis. This procedure appears to be a reproducible
      and clinically relevant model for evaluating FS in vascular surgery. Consenting
      adult patients (n = 28) undergoing placement of a PTFE graft (6 mm) were
      randomized to either the treatment group using FS (Hemaseel APR, Haemacure Corp.,
      Sarasota, FL) or control comparator groups (four) of bovine thrombin (T)
      (Thrombogen, GenTrac Inc., Middleton, WI), pressure (P), bovine thrombin
      (Thrombogen, GenTrac Inc.) -soaked cellulose sponges (TG) (Gelfoam, Upjohn Co.,
      Kalamazoo, MI), or oxidized regenerated cellulose (S) (Surgicel, Johnson &
      Johnson, New Brunswick, NJ). All patients received heparin (3000 IU intravenous
      push) before placement of vascular clamps. The mean time to hemostasis was 29.3
      seconds for FS, 147.4 seconds for T, 872.2 seconds for P, 346 seconds for TG, and
      1044.5 seconds for S. There were no significant adverse events. FS appeared to be
      a superior hemostatic agent in these vascular procedures. No complications from
      FS were noted.

PMID- 12206611
TI  - Ruptured umbilical hernia in a case of alcoholic cirrhosis with massive ascites.
AB  - Umbilical hernias are common in patients with cirrhosis of the liver and ascites.
      However, spontaneous rupture of the hernia is not frequently seen. This is a
      serious complication and carries a high mortality. A search of the literature
      shows that patients have been managed both operatively and nonoperatively for
      this condition. We present a case of spontaneous rupture of an umbilical hernia
      in a patient with cirrhosis and ascites which was managed successfully with
      hernia repair.

PMID- 12206612
TI  - Breast cancer recurrences in elderly patients after lumpectomy.
AB  - Approximately half of breast cancers occur in women 65 years or older. Some
      studies suggest that breast cancer may be a more indolent disease in this group
      of patients. Debate exists over the appropriate treatment of these women as they
      are significantly underrepresented in breast cancer research studies. As a result
      of comorbid conditions and patient refusal many are often treated less
      aggressively than their younger counterparts. This study investigated the
      recurrence rate in elderly breast cancer patients who had undergone lumpectomy as
      their primary treatment at our institution. A chart review was conducted on
      breast cancer patients treated from January 1, 1995 through September 26, 2000
      with lumpectomy performed at Wake Forest University Baptist Medical Center. Study
      criteria included female gender and age greater than 65 years, first incidence of
      breast cancer, no evidence of distant disease at presentation, and availability
      follow-up assessed by clinical examination and mammogram records. Clinical and
      pathological features and treatments were evaluated. The Cox proportional-hazards
      model, Fisher's exact test, and analysis of variance were used for statistical
      analysis. One hundred thirteen patients met study criteria. The stage
      distribution was as follows: stage 0 (T(IS)), 16 per cent; stage I, 56 per cent;
      stage IIA, 24 per cent; and stage IIB, 4 per cent. With a median follow up of 30
      months six (5%) patients developed locoregional recurrence, four (4%) developed
      contralateral cancer, and two patients (2%) developed distant disease. Mean time
      to recurrence was 21 months. No patient has died of breast cancer, but one
      patient died of a second malignancy. Radiation therapy and tamoxifen decreased
      recurrence as compared with no adjuvant treatment or with adjuvant radiation only
      (P < 0.05). We conclude that patients treated with tamoxifen and radiation
      therapy had a significantly smaller risk of recurrences than those treated with
      lumpectomy only or those receiving radiation alone. This supports similar
      treatment patterns recommended for younger patients. Women over 65 years of age
      should be carefully evaluated for adjuvant therapy.

PMID- 12206613
TI  - Right-sided diverticulitis--surgical and nonsurgical treatment: two case reports
      and review of the literature.
AB  - Right-sided diverticulitis is difficult to distinguish from other sources of
      right-sided abdominal pain. Diverticula localized to the right colon occur at a
      rate of 6.6 to 14 per cent. Two types of diverticula have been described in the
      right colon on the basis of etiologic and pathologic features: multiple
      diverticula and solitary diverticulum of the cecum. The most common clinical
      presentation of right-sided colonic diverticula is an acute inflammatory
      complication, which is difficult to distinguish from other causes of right iliac
      fossa pain. We present two case reports on right-sided diverticulitis with one
      treated surgically and the other treated nonsurgically. The clinical
      manifestations, differential diagnosis and management options are discussed
      including a review of the literature.

PMID- 12206614
TI  - International outreach for pediatric surgical subspecialists.

PMID- 12206615
TI  - Developmental risks and protective factors for influencing cognitive outcome at 5
      1/2 years of age in very-low-birthweight children.
AB  - In a population-based follow-up study (the Stockholm Neonatal Project), 182
      children with a birthweight of 1500 g or less (very-low birthweight: VLBW) and a
      control group of 125 children born healthy at term were examined with the
      Wechsler Preschool and Primary Scale of Intelligence-Revised (WPPSI-R) and a
      neuropsychological test battery (Nepsy) at 5 1/2 years of age. The WPPSI-R
      results of the VLBW children fell well within the normal range: WPPSI-R full
      scale IQ 95.7, verbal subscale IQ 99.9, and performance subscale IQ 91.6.
      Nevertheless, the control group had significantly better results than the VLBW
      group which could be attributed to the greater variability of the VLBW group,
      with a larger proportion falling in the lower area of the IQ distribution,
      especially on the performance subscale. Likewise, the control group displayed
      better executive function (Nepsy). Paternal education was equal in the two groups
      and was the single most important predictor of IQ, possibly acting as a
      protective factor. The need for glasses or lenses was inversely associated with
      all IQ measures and severe retinopathy of prematurity (ROP) had the most negative
      impact on full-scale and performance IQ. These two IQ measures were also
      negatively associated with intrauterine growth retardation late in pregnancy. We
      conclude that VLBW children, in the absence of these identified risk factors,
      have normal cognitive development.

PMID- 12206616
TI  - Intelligence in preterm children at four years of age as a predictor of school
      function: a longitudinal controlled study.
AB  - The aim of the study was to examine whether school performance was reduced in
      children with very-low birthweight beyond what could be explained by the deficit
      in intelligence-score at 4 years of age. Participants (n=333) examined at 4 years
      of age included three subgroups on the basis of birthweight: very-low birthweight
      (VLBW < 1501 g; n=102), low birthweight (LBW 1500-2300 g; n=139), and normal
      birthweight (NBW > or = 2500 g; n=92). The general cognitive index index (CGI)
      from the McCarthy Scales of Children's Abilities was used as an intelligence
      measurement at this assessment. At 18 to 20 years of age a telephone interview
      concerning school performance was conducted. Two hundred and fifty-seven
      participants (53% male, 47% female) entered the analysis. A model with School
      Performance score after the last year of compulsory school as the outcome
      variable, and McCarthy GCI and birthweight group as predicting variables, was
      used in linear regression analyses. Twenty-four per cent of the variance was
      explained. Birthweight had no influence in this model. In conclusion, the study
      did not find that birthweight influenced school performance beyond that
      represented by the McCarthy GCI found at age 4 years.

PMID- 12206617
TI  - Long-term follow up of childhood tuberculous meningitis.
AB  - The purpose of the present study was to determine the long-term outcome of 76
      children (40 females and 36 males) diagnosed and treated with modern
      antituberculosis drugs. The median age of the children on admission was 29.5
      months and on follow-up 9 years. Antituberculosis therapy consisted of daily
      isoniazid (20 mg/kg), rifampicin (20 mg/kg), ethionamide (20 mg/kg), and
      pyrazinamide (40 mg/kg) for 6 months. Twenty-three children received daily
      prednisone (2-4 mg/kg) for the first month of treatment. Raised intracranial
      pressure was actively monitored and treated. Patients with non-communicating
      hydrocephalus received ventriculo-peritoneal shunts shortly after admission while
      communicating hydrocephalus was treated with oral acetazolamide (100 mg/kg/day)
      and furosemide (1 mg/kg/day) in 3-4 divided doses. Communicating hydrocephalus
      that did not respond to this regimen within the first month of treatment also
      underwent ventriculo-peritoneal shunting. Only 20% of children were functionally
      completely normal at follow-up. Main areas of functional deficit were cognitive
      impairment (80%), poor scholastic progress (43%), and emotional disturbance
      (40%). Twenty-five per cent of children had evidence of motor impairment, but all
      could walk and only 5 of 76 children (6% of total) were unable to run. One child
      was blind but no child had sensori-neural deafness. It was concluded that these
      disabilities in children from mainly deprived socioeconomic backgrounds have
      serious implications for their future social, academic, and career prospects. A
      high index of suspicion of TBM in high tuberculosis incidence communities will
      help prevent the morbidity documented in this study.

PMID- 12206618
TI  - Automatic processing of tones and speech stimuli in children with specific
      language impairment.
AB  - It is well known from behavioural experiments that children with specific
      language impairment (SLI) have difficulties discriminating consonant-vowel (CV)
      syllables such as /ba/, /da/, and /ga/. Mismatch negativity (MMN) is an auditory
      event-related potential component that represents the outcome of an automatic
      comparison process. It could, therefore, be a promising tool for assessing
      central auditory processing deficits for speech and non-speech stimuli in
      children with SLI. MMN is typically evoked by occasionally occurring 'deviant'
      stimuli in a sequence of identical 'standard' sounds. In this study MMN was
      elicited using simple tone stimuli, which differed in frequency (1000 versus 1200
      Hz) and duration (175 versus 100 ms) and to digitized CV syllables which differed
      in place of articulation (/ba/, /da/, and /ga/) in children with expressive and
      receptive SLI and healthy control children (n=21 in each group, 46 males and 17
      females; age range 5 to 10 years). Mean MMN amplitudes between groups were
      compared. Additionally, the behavioural discrimination performance was assessed.
      Children with SLI had attenuated MMN amplitudes to speech stimuli, but there was
      no significant difference between the two diagnostic subgroups. MMN to tone
      stimuli did not differ between the groups. Children with SLI made more errors in
      the discrimination task, but discrimination scores did not correlate with MMN
      amplitudes. The present data suggest that children with SLI show a specific
      deficit in automatic discrimination of CV syllables differing in place of
      articulation, whereas the processing of simple tone differences seems to be
      unimpaired.

PMID- 12206619
TI  - High incidence of language disorder in children with focal epilepsies.
AB  - To investigate the relationship between the presence of language disorder, type
      of epilepsy, and epileptic seizures in childhood, language levels, types of
      language impairment, and aetiologies were examined in 109 children, aged between
      5 and 17 years, attending a national children's epilepsy assessment unit over a 4
      year period. There were 70 males and 39 females. Median age was 11 years 4 months
      (range 5 to 18 years 9 months). In addition to neurological assessment,
      simultaneous video and EEG monitoring and prolonged ambulatory EEG, each child
      underwent a comprehensive series of multidisciplinary tests, including
      intelligence, language, and communication assessments. Classification of seizures
      and epilepsy syndromes was agreed in conference by a physician specializing in
      childhood epilepsies, a paediatric neurologist, and a neuropsychiatrist. Other
      test procedures were administered by a speech and language pathologist with
      assistance from a neuropsychologist when relevant. Level of language disability
      in these children was associated with a range of aetiological factors. Evidence
      was found of a significant number of associations between focal epilepsies,
      certain seizure types, and language disorder. Of the 46 (42.2%) children with
      language disorders in the research sample, 30 had localization-related epilepsies
      and a further three had epilepsies which were undetermined as to whether focal or
      generalized. Children with focal epilepsies were 30% more likely to have language
      disorder than other language disability subtypes. The research demonstrated a
      clear though often subtle association between focal (localization-related)
      epilepsy and language disorder, indicating an increased risk in this patient
      group. Children with simple or complex partial seizures were more likely to have
      language disorder than other language disability subtypes; they also tended to
      have the lowest number of seizure types per case. This is of importance to
      clinicians managing children with epilepsy and has implications for their
      educational and social welfare.

PMID- 12206620
TI  - Prevalence and selected characteristics of childhood vision impairment.
AB  - The objective of this study was to examine the descriptive epidemiology of vision
      impairment among 6- to 10-year-old children in metropolitan Atlanta, Georgia,
      USA. Children with vision impairment (n=310; 42% black, 56% white; 57% male, 43%
      female), defined as a best corrected visual acuity in the better eye of 20/70 or
      worse, were identified through the Metropolitan Atlanta Developmental
      Disabilities Surveillance Program. The overall prevalence was 10.7 per 10,000
      children. Fifty-nine percent had low vision; nearly two-thirds had coexisting
      disabilities. Educational program varied by vision impairment severity and
      presence of coexisting disabilities. The common presence of coexisting
      disabilities emphasizes the importance of multidisciplinary services. The
      inclusion of case ascertainment sources other than vision impairment classes is
      critical to ensure an accurate prevalence rate and unbiased description of
      children with vision impairment.

PMID- 12206621
TI  - Oculomotor dysfunction in cerebral visual impairment following perinatal hypoxia.
AB  - The aim of the study was to describe ocular motility in a sample of 56 patients
      affected by cerebral visual impairment (CVI) of hypoxic-ischemic origin. The
      sample consisted of 56 participants (37 males and 19 females), ranging in age
      from 2 to 16 years. In all cases CVI was associated with MRI-verified damage of
      the cerebral visual system. A complete ophthalmologic and neurological assessment
      was performed. Behaviour of gaze was studied in four conditions: during scanning
      of the surrounding environment, during fixation, execution of saccades, and
      pursuing. In addition, strabismus, nystagmus, and paroxysmal ocular deviations
      were evaluated. Ocular motility was studied by video recording the patients' eye
      motility during orthoptic examination. Each pattern of ocular motility studied
      revealed profound alterations in all the individuals examined. Typical features
      of ocular motility in CVI were: paroxysmal ocular deviations (present in 78%);
      the presence of variable angle strabismus (86%); and defective coordination of
      saccades (93%). Exploration of the environment and fixation were also impaired
      (88% and 84%, respectively). Disorders of initiation and performing saccades,
      absence of smooth pursuit, vergence abnormalities, nystagmus beats, instability
      of fixation, and difficulty in the systematic exploration of the environment were
      observed. These abnormalities characterize lack of gaze coordination found in
      children with brain damage. An early and detailed evaluation of ocular motility
      in individuals with CVI is important, especially when rehabilitation intervention
      is intended.

PMID- 12206622
TI  - Double-blind comparison study of two doses of botulinum toxin A injected into
      calf muscles in children with hemiplegic cerebral palsy.
AB  - Despite several trials showing reductions in tone and improvements in gait, the
      relation between botulinum toxin A (BTX-A) dose and response has rarely been
      investigated. A double-blind randomized comparison of two doses of BTX-A in
      children with spastic hemiplegic cerebral palsy (n=48, mean age 7 years 6 months,
      range 3 to 15 years) was undertaken. The two doses selected were representative
      of the lower and the higher doses used in clinical practice (24 units/kg body
      weight and 8 units/kg body weight). Using gait analysis we evaluated hip, knee,
      and ankle joint kinetics and sagittal kinematics throughout the gait cycle.
      Gastrocnemius muscle length was calculated at each visit using the method
      described by Eames and used as our primary outcome measure. Our secondary outcome
      variable was maximum ankle angle measured during stance and swing phases. In
      summary, we found that there were indications that 24 units/kg body weight was
      more effective and lasted longer than 8 units/kg. Analysis in terms of absolute
      dose suggested that the dose-response correlation was non-linear, and that the
      optimal range lay between 200 and 500 units BTX-A (Dysport).

PMID- 12206624
TI  - Two distinct forms of minor neurological dysfunction: perspectives emerging from
      a review of data of the Groningen Perinatal Project.

PMID- 12206623
TI  - Psychomotor development in children with early diagnosed giant interhemispheric
      cysts.
AB  - Systematic studies of cognitive development in individuals with congenital giant
      interhemispheric cysts (GIC) without neurosurgical intervention are rare.
      However, data from such studies are of great importance in deciding whether or
      not to perform cerebral shunting in otherwise asymptomatic patients. In this
      study, psychomotor function was examined in 13 children (three females, 10 males;
      mean age at follow-up: females 1 year 6 months, males 3 years 2 months; age
      range: females 13 months to 4.2 years, males 10 months to 10 years) all diagnosed
      with GIC during the neonatal period after indicative foetal ultrasound. Eight
      patients received neurosurgical treatment due to increased intracerebral pressure
      during the first year of life. Psychomotor development was evaluated using
      Griffith's Psychomotor Developmental Scales, the Sniders-Oomen Non-verbal
      Intelligence Scale for Young Children and the Kaufmann Assessment Battery for
      Children. The majority of patients showed normal intelligence, irrespective of
      the presence or absence of neurosurgical intervention. Evidence was found that
      the cognitive outcome might be related to an association of GIC with agenesis of
      the corpus callosum or additional congenital cerebral malformations, such as
      gyration anomalies. Main postoperative complications were chronic subdural
      effusions with spastic cerebral (hemi)-paresis; were present in three patients.
      In view of the risk of severe postoperative neurological complications and a
      comparable psychomotor development in patients without neurosurgical treatment,
      recommendations for early neurosurgical intervention in otherwise asymptomatic
      patients with a foetal or neonatal diagnosis of GIC should be viewed with
      caution.

PMID- 12206625
TI  - Rasmussen's encephalitis followed by lupus erythematosus.
AB  - A 6-year-old female presented with right hemichorea, initially thought to be post
      streptococcal, which subsequently progressed to a right dystonic hemiplegia. At 7
      1/2 years she developed right focal and secondary generalized tonic-clonic
      seizures. These became intractable. A brain biopsy was consistent with
      Rasmussen's encephalitis (RE). At 9 1/2 years the child underwent a left
      hemispherectomy making a good recovery with resolution of seizures. At 12 years
      she presented with recurrent episodes of abdominal pain, fever, and malar rash
      with serological evidence of systemic lupus erythematosus (SLE). A possible link
      between RE and SLE is discussed.

PMID- 12206626
TI  - Techniques for phase correction in coherent ultrasound imaging systems.
AB  - The problem of phase aberrations modeled as a near field thin phase screen is
      considered. Here three new techniques for phase aberration correction are
      presented. In the "central element" correction technique the echo-signal at each
      array element is aligned with the signal at the central array element. In the
      "variable speckle look-back" correction technique the signal at each array
      element is aligned with the sum of signals from all previously corrected
      elements. In the "variable central speckle look-back" correction technique the
      signal at each array element is aligned with the sum of signals from the central
      group of all previously corrected elements. The performance of new techniques for
      phase aberration correction is tested by means of simulating the point-spread
      function for both point and speckle targets. The results of simulation show that
      the new techniques have the better accuracy of phase correction than the
      classical "neighbor element" technique.

PMID- 12206627
TI  - Elastic constants of the SrLaAlO4 and SrLrGagaO4 crystals measured at ultrasonic
      and hypersonic oustic frequencies.
AB  - Elastic constants measured by Brillouin light-scattering experiments were
      compared with results estimated from the pulse-echo-overlap method for the
      ultrasonic frequency to find dispersion in their values. In this way Brillouin
      hypersonic experiments complete the ultrasonic results. The present investigation
      includes a careful analysis of the accuracy of the results. The measured values
      of elastic constants suggest a weak dispersion in acoustic wave velocities.
      However, given the magnitude of the experimental errors, it is difficult to
      conclude about the dispersion.

PMID- 12206628
TI  - On the verification of the applicability of the orthotropic plate wave theory to
      paper.
AB  - In the literature one basic work can be found that describes an attempt to verify
      the applicability of the orthotropic plate wave theory to paper. In the present
      study we have repeated the key experiment and also modified the original
      experimental set-up to be able to make new complementary measurements. The
      performed verification attempt is based on a key experiment in which an
      ultrasonic resonance method is used. When it is applied to paper, a second
      resonance can be observed in addition to the one that originates from the
      asymmetric A0 mode. The result of the verification experiment is conclusive only
      if the source of this second resonance is the symmetric S0 mode. Our results show
      that the second resonance is not generated by the S0 mode. Instead, they indicate
      that the source is a longitudinal wave propagating in the thickness direction of
      the paper. We therefore conclude that the applicability of the orthotropic plate
      wave theory to paper cannot be verified by performing the key experiment that is
      described in the literature.

PMID- 12206629
TI  - Measurement of viscosity and shear wave velocity of a liquid or slurry for on
      line process control.
AB  - An on-line sensor to measure the density of a liquid or slurry, based on
      longitudinal wave reflection at the solid-fluid interface, has been developed by
      the staff at Pacific Northwest National Laboratory. The objective of this
      research is to employ shear wave reflection at the solid-fluid interface to
      provide an on-line measurement of viscosity as well. Both measurements are of
      great interest for process control in many industries. Shear wave reflection
      measurements were conducted for a variety of liquids. By analyzing multiple
      reflections within the solid (only 0.63 cm thick-similar to pipe wall thickness)
      we increased the sensitivity of the measurement. At the sixth echo, sensitivity
      was increased sufficiently and this echo was used for fluid interrogation. Shear
      wave propagation of ultrasound in liquids is dependent upon the viscosity and the
      shear modulus. The data are analyzed using the theory for light liquids (such as
      water and sugar water solutions) and also using the theory for highly viscous
      liquids (such as silicone oils). The results show that, for light liquids, the
      shear wave reflection measurements interrogate the viscosity. However, for highly
      viscous liquids, it is the shear wave modulus that dominates the shear wave
      reflection. Since the density is known, the shear wave velocity in the liquid can
      be determined from the shear wave modulus. The results show that shear wave
      velocities in silicone oils are very small and range from 315 to 2389 cm/s. Shear
      wave reflection measurements are perhaps the only way that shear wave velocity in
      liquids can be determined, because the shear waves in liquids are highly
      attenuated. These results show that, depending on the fluid characteristics,
      either the viscosity or the shear wave velocity can be used for process control.
      There are several novel features of this sensor: (1) The sensor can be mounted as
      part of the wall of a pipeline or tank or submerged in a tank. (2) The sensor is
      very compact and can be located within the process stream. (3) The sensor can
      interrogate and characterize very attenuative liquids or slurries because the
      sensor operation depends upon reflection at the interface between the solid and
      the fluid, rather than on transmission through a liquid. (4) The sensor
      performance is not affected by fluid flow rate, entrained air, or vibration.

PMID- 12206630
TI  - Reconstruction of ultrasonic fields by deconvolving the hydrophone aperture
      effects. I. Theory and simulation.
AB  - In many ultrasound applications-especially in the area of medical diagnostics
      conventional sensors and particularly piezoelectric hydrophones do not comply
      with the requirements for "point detectors". It therefore suggests itself to
      develop methods, which allow ultrasonic fields to be reconstructed from the
      spatially averaged measurement values with the necessary spatial resolution. In
      this publication, this task will be treated as an inverse problem. It will be
      shown by simulations that it is possible with the aid of reconstruction methods
      to invert the aperture effects of the sensor. Three different reconstruction
      methods are tested: (1) Wiener's method furnishes the best approximation of the
      field to be reconstructed in the sense of the minimum mean square error. (2) The
      power spectral equalization method is based on equalization between the spatial
      power spectral densities of the field to be reconstructed and that of its
      estimated value. (3) With the maximum a-posteriori method, the maximum a
      posteriori probability density function for the reconstructed field is searched.
      The results of this paper show that the quality of reconstruction depends on the
      signal-to-noise ratio (SNR) and the spatial frequency bandwidth of the sound
      field investigated. Good quality reconstructions were obtained at correlation
      coefficients larger than 0.995 and an SNR of at least 40 dB. In general, the
      quality of reconstruction decreases with decreasing SNR and is unacceptable at
      SNR = 20 dB. The quality also decreases with decreasing axial distance from the
      source that is with increasing spectral frequency bandwidth.

PMID- 12206631
TI  - Reconstruction of ultrasonic fields by deconvolving the hydrophone aperture
      effects. II. Experiment.
AB  - The correction of the averaging effect of finite-size hydrophones is at present
      realized by various methods which are based on idealized models for the sound
      field and thus are valid only to a limited extent. In the present article three
      methods for inverting the aperture effects of the hydrophone viz. the Wiener
      method, the power spectral equalization (PSE) method and the maximum a posteriori
      (MAP) method, are experimentally tested and their efficiency is compared. It is
      shown that both for a rectangular and for a circular hydrophone aperture all
      three methods are suitable to reconstruct complex sound field structures from
      spatially averaged data. The results of this paper confirm the finding of Part I
      [Ultrasonics 39 (2002) 603], i.e. the quality of reconstruction depends on the
      spatial frequency bandwidth of the sound field investigated. Good quality
      reconstructions are obtained when the effective dimensions of the hydrophone's
      sensing area are directly derived from the spatial frequency spectrum of the
      measurement signal. The Wiener method and the MAP method are superior to the PSE
      method, since the PSE filter does not take phase information into account. For
      the Wiener and the MAP method normalized correlation coefficients, r(pp), between
      the reconstructed sound pressure field and that of a reference measurement of
      typically 0.97 are obtained provided that the axial distance is not too small.
      Although the working frequency used for the experiments is rather low, it can be
      expected that the results obtained are applicable at higher frequencies provided
      that the complex spatial transfer function is determined with the necessary high
      precision.

PMID- 12206632
TI  - The frequency width of symmetric modes of an aluminum plate: manifestation of a
      complex slowness on a frequency spectrum.
AB  - The evolution of the experimental frequency width of symmetric modes of an
      aluminum plate is studied as a function of the angle of incidence below the first
      critical angle. It is found that the frequency width predicted by resonant
      scattering theory, corrected for the directivity of emitter and receiver,
      generally explains the experimental frequency width well. However, large
      discrepancies remain for the frequency width of the S1 mode at angles of
      incidence larger than 9 degrees. It is demonstrated that these are caused by not
      taking into account the complex nature of the slowness of the plate mode. This
      suggests that there is a need for a theory that models the interaction of a beam
      of ultrasound, bounded in space and time, with an elastic plate.

PMID- 12206633
TI  - Simulations of circular 2D phase-array ultrasonic imaging transducers.
AB  - Theoretical simulations of the pulse-echo beam forming of two-dimensional (2D)
      circular planar phase-array ultrasound transducers were conducted for the
      optimization of the effective architectures. These results were compared with
      equivalent linearly reticulated 2D phase-array transducer configurations. It is
      predicted that ultrasound imagers based on circular 2D phase-array transducers
      will out perform the other architectures for several medical applications. This
      study was motivated by the recent demonstration of micromachining of high-density
      circular as well as linear reticulated 2D phase-array transducers, to achieve
      real-time high-resolution completely electronic steerable volumetric medical
      noninvasive ultrasound imaging.

PMID- 12206634
TI  - A study on the friction of a self-correction ultrasonic stepping motor.
AB  - An experiment has been carried out to investigate the self-correction function of
      a self-correction ultrasonic stepping motor. When a slider (rotor) is placed on a
      vibrating beam (stator), it will stay at a stable equilibrium position. If the
      slider is slightly moved off the equilibrium position, a restoring force will
      urge the slider back towards its equilibrium position. The experimental result
      shows that the position of the maximum restoring force on the slider differs from
      that predicted by using the linear theory. Study found that when a quadratic form
      is assumed for the dynamic friction coefficient, the theoretical and experimental
      results are in good agreement.

PMID- 12206635
TI  - Duration of adjuvant chemotherapy; anthracyclines, taxanes and novel agents--more
      or less.

PMID- 12206636
TI  - Survey of UK breast radiotherapy techniques: background prior to the introduction
      of the quality assurance programme for the START (standardisation of
      radiotherapy) trial in breast cancer.
AB  - As an integral part of a quality assurance programme, this survey was undertaken
      to establish precise details of breast radiation techniques used within centres
      expressing an interest to participate in the START Trial--a U.K. multi-centre
      randomised trial of different dose fractionation schedules for breast cancer. A
      questionnaire was circulated between November 1997 and January 1999 to 56 U.K.
      radiotherapy centres. This covered specific details of patient immobilisation,
      technique and dose fractionation when treating breast or chest wall,
      supraclavicular fossa and axilla and when directing a boost to the tumour bed.
      Variations in technique, incorporating immobilisation, treatment energy and dose
      prescription span the entire radiation treatment process from localisation to
      planning and subsequent treatment. A range of dose/fraction/time schedules were
      used for tangential fields, nodal fields and the tumour bed boost. As part of the
      quality assurance programme for the START Trial this independent review of breast
      radiotherapy practice has provided a baseline of techniques used by centres prior
      to participating in the trial. It has also presented a view of the complexity of
      the issues to enable the design of the next phase of the quality assurance
      programme. Adherence to the trial protocol will ensure acceptable technique and
      dosimetry across centres.

PMID- 12206637
TI  - Radiotherapy for perianal Paget's disease.
AB  - The role of radiotherapy in the management of perianal Paget's disease (PPD) is
      not well defined in clinical practice or within the medical literature. We
      present 6 cases, document the radiotherapy details and review our results. A
      comprehensive literature search has been undertaken attempting to identify all
      published cases of PPD and survey the number receiving radiotherapy. To further
      define the role for radiotherapy in PPD these cases have been reviewed. Published
      results are sporadic and often poorly documented with respect to technical
      radiotherapy details. Two main roles for radiotherapy in PPD were found. One is
      as primary treatment for in situ or invasive disease and the other is following
      surgical relapse of in-situ or invasive disease. Other possible uses of
      radiotherapy in PPD such as neoadjuvant or adjuvant treatment or chemo
      radiotherapy are discussed. Results of radiotherapy treatment for case of in situ
      and invasive disease are presented. We disagree with the view in some areas of
      the surgical literature that radiotherapy has no place in the management of the
      disease. Despite a thorough surveying of the literature however, precise
      recommendations on several areas of the technical radiotherapy treatment such as
      dose-fractionation schedules and field margins are difficult because of the small
      number of cases and poor general documentation. Our practice recommendations are
      presented. Radiotherapists should be encouraged to publish their experience in
      this disease to help define further a role for this treatment.

PMID- 12206638
TI  - Successful chemoradiotherapy for anal cancer despite previous radical
      radiotherapy for gynaecological malignancy.
AB  - Repeat radical irradiation of the pelvis is generally not undertaken because of
      concerns regarding normal tissue damage; in particular to small bowel, bladder
      and bone. Two patients with carcinoma of the anal canal are presented who had
      previously been treated by radical pelvic radiotherapy for gynaecological
      malignancy. Both were re-treated with radical radiotherapy to the pelvis with
      concomitant chemotherapy. A complete remission of anal cancer was achieved in
      both patients with minimal acute and late toxicities.

PMID- 12206639
TI  - Brain as sanctuary site of relapse in germ cell cancer patients previously
      treated with chemotherapy.
AB  - BACKGROUND: Post chemotherapy isolated relapse to the brain of germ cell cancer
      is potentially curable. PATIENTS AND METHODS: We reviewed the experience of germ
      cell cancer with cerebral metastases at the CRC Wessex Medical Oncology Unit in
      Southampton. Patients were classified according to their presentation (initial
      diagnosis, solitary relapse or widespread). Treatment and outcome of these
      patients is presented and compared with previous series. RESULTS: Of 1049
      patients treated for metastatic germ cell cancer, 15 were diagnosed with cerebral
      metastases. Six patients had cerebral sanctuary site relapse, and underwent
      resection and cranial irradiation. Four of these are continuously disease free
      after treatment at 2, 67, 96, and 145 months from therapy, another is receiving
      chemotherapy for limited systemic relapse and the sixth has relapsed and died.
      Three further patients relapsed with cerebral disease in the presence of active
      disease elsewhere and each progressed and died. The final six patients had
      cerebral disease at presentation of whom five have progressed and died.
      CONCLUSIONS: Isolated cerebral metastases occurring after successful systemic
      chemotherapy for germ cell cancer are curable. An aggressive salvage approach
      with surgery followed by radiotherapy is indicated.

PMID- 12206640
TI  - Repeated AFP surge: an unusual and potentially misleading tumour marker
      phenomenon.

PMID- 12206641
TI  - Conformal radiotherapy to the prostate: are bigger fields better?

PMID- 12206642
TI  - A dose-volume histogram analysis of the seminal vesicles in men treated with
      conformal radiotherapy to 'prostate alone'.
AB  - BACKGROUND AND PURPOSE: There is no consensus on whether the seminal vesicles
      should be included in the clinical target volume (CTV) for radiotherapy of
      localized prostate cancer. To inform the debate, we have undertaken a dose-volume
      histogram (DVH) analysis of the seminal vesicles in patients treated with
      escalated dose conformal radiation to 'prostate alone'. MATERIAL AND METHODS:
      Twenty-five consecutive patients receiving conformal radiation to the prostate,
      to a dose of 75.6 Gy in 42 daily fractions, were studied. The CTV was defined as
      the prostate only, and the planning target volume (PTV) was defined by a 10 mm
      margin, except posteriorly where the margin was 7 mm. DVHs were calculated for
      the entire seminal vesicles, and for 6 mm segments through the seminal vesicles.
      RESULTS: Incorporating a correction for organ motion, the D90 (minimum dose
      received by 90% of the volume of interest) for the most inferior 6 mm volume of
      the seminal vesicles (SV1) ranged from 25 to 70 Gy, and the percentage volume of
      SV1 receiving 50 Gy ranged from 47-100%. Using a D90 of 50 Gy as a cut-off, eight
      of the 25 patients had unacceptably low-dose coverage of SV1. CONCLUSIONS:
      Escalated dose conformal radiation to the 'prostate alone' does not ensure
      adequate dose coverage of even the most inferior 6 mm of the seminal vesicles. We
      consider such treatment acceptable in patients at low risk of seminal vesicle
      involvement (T1/2ab, Gleason < or = 7, PSA < 10 ng/ml). In higher risk patients,
      if it is deemed necessary to treat the possibility of sub-clinical seminal
      vesicle involvement, this should be reflected in the definition of the CTV.

PMID- 12206643
TI  - Unresolved issues in the management of locally advanced non-metastatic pancreas
      cancer.

PMID- 12206644
TI  - Locally advanced pancreatic cancer treated with radiation and 5-fluorouracil.
AB  - A retrospective analysis was performed, in a single institution, of patients with
      locally advanced pancreatic carcinoma without evidence of distant metastases, who
      were treated with chemoradiation. Between 1994 and 2000, 24 patients were treated
      with radiation and 5-fluorouracil (5-FU). The standard dose of radiation
      prescribed was 45 Gy to the 95% isodose in 25 fractions over 5 weeks. 5-FU was
      given as a 60 min infusion on days 1-5 and 29-33 at 350 mg/m2, following low dose
      folinic acid. Actuarial survival, local control and toxicity rates were assessed
      for the group. The median survival was 12 months, with a 48% 1-year survival and
      a 29% 2-year survival. The median time to progression was 8 months. The treatment
      was well tolerated and all patients achieved 100% compliance. In terms of
      radiological tumour response, five patients (22%) had a complete response, 10
      patients (45%) demonstrated partial tumour shrinkage and a further three
      additional patients had radiological stable disease. The majority of patients
      experienced a symptomatic improvement. Chemoradiation can produce effective local
      control with symptomatic improvement in patients with localised carcinoma of the
      pancreas. Further studies are needed to determine the most effective combination
      of chemotherapy agents, combined with radiotherapy in the management of this
      disease.

PMID- 12206645
TI  - Coronary artery brachytherapy.
AB  - Coronary artery disease is the leading cause of mortality in the West with over
      1.2 million angioplasties performed annually. Despite the introduction of stents,
      restenosis occurs in 30-40% of vessels, which until recently has only been
      treated effectively by coronary artery bypass surgery. Coronary artery
      brachytherapy appears to provide an alternative, less invasive remedy. The
      mechanisms of restenosis and how these are inhibited by radiation are described
      here. The practicalities of radiation delivery and the history of the development
      of intravascular radiation as an effective clinical tool are outlined. Finally,
      the pitfalls of the current technology and the areas in which future research
      must be targeted for the field to develop are discussed.

PMID- 12206646
TI  - Successful salvage of relapsed adults Wilms' tumour with high dose chemotherapy
      and autologous peripheral blood stem cell rescue.

PMID- 12206647
TI  - Health-related quality of life in patients on radiotherapy waiting lists.

PMID- 12206648
TI  - Health-related quality of life in patients on radiotherapy waiting lists.

PMID- 12206649
TI  - Is octreotide useful for hepatic metastases due to non-neuroendocrine primary
      tumors?

PMID- 12206650
TI  - CHART and chemotherapy.

PMID- 12206651
TI  - The proportion of NSCLC patients eligible for CHART may be much higher than
      originally anticipated.

PMID- 12206652
TI  - Mac1, a fission yeast transmembrane protein localizing to the poles and septum,
      is required for correct cell separation at high temperatures.
AB  - Schizosaccharomyces pombe represents a genetic model system for studying cell
      polarity and division in eukaryotes. We report here the identification of Mac1, a
      novel fission yeast protein that localized predominantly to the cell tips and
      septum. Sequences corresponding to roughly the first 180 amino acids of Mac1,
      which exhibited weak homology to the transmembrane domains of the Aspergillus
      Pall protein [Mol. Microbiol. 30 (1998) 259], were found to specify localization
      to the cell periphery. The other 574 amino acids of Mac1 localized to the
      cytoplasm when expressed alone, thus suggesting that the N-terminal part of Mac1
      functions as a plasma membrane anchor for the rest of the protein. In pom1 null
      mutant cells, which never switch from unipolar to bipolar growth but, instead,
      grow exclusively at the randomly chosen end [Genes Dev. 12 (1998) 1356], Mac1
      was, nevertheless, found at both poles, thus suggesting that Mac1 does not
      specifically localize to the sites of growth. mac1 null mutant cells had no overt
      phenotype at 22-32 degrees C, but, nevertheless, displayed a marked decrease in
      viability at 34-36 degrees C, accompanied by severe separation defects.
      Overexpression of mac1 resulted in similar defects. Our data suggest that a
      correct dosage of Mac1 is needed for correct cell separation at elevated
      temperatures of growth.

PMID- 12206653
TI  - Subcellular distribution of the acidic ribosomal P-proteins from Saccharomyces
      cerevisiae in various environmental conditions.
AB  - The yeast ribosomal "stalk"--a lateral protuberance on the 60S subunit--consists
      of four acidic P-proteins, P1A, P1B, P2A and P2B, which play an important role
      during protein synthesis. Contrary to most ribosomal proteins, which are rapidly
      degraded in the cytoplasm, P-proteins are found as a cytoplasmic pool and are
      exchanged with the ribosome-bound proteins during translation. As yet,
      subcellular trafficking of P-proteins has not been extensively investigated.
      Therefore, we have characterized--using immunological approaches--the cellular
      distribution of P-proteins in several environmental conditions, characteristic of
      yeast cells, such as growth phases, and heat-, osmotic-, and oxygen-stress. Using
      the western blotting approach, we have shown P-proteins to be present in constant
      amounts on the ribosomes, despite their exchangeability with the cytoplasmic
      pool, and regardless of environmental conditions. On the other hand, P-protein
      level in the cytoplasm decreased sharply throughout the consecutive growth
      phases, but was not affected by several stress conditions. Applying the electron
      microscopic technique and immunogold labeling, we have found that P-proteins are
      located in two cell compartments. The first one is the cytoplasm and the second
      one--an unexpected place--the cell wall, where P-proteins are fully
      phosphorylated. Moreover, the existence of P-proteins on the cellular wall is not
      affected by various environmental conditions.

PMID- 12206654
TI  - Heterozygosity in MAT locus affects stability and function of microtubules in
      yeast.
AB  - The dynamic nature of microtubules is important for their cellular function and
      is tightly regulated by the cell cycle machinery and through other pathways that
      act on microtubule-associated proteins. Recently, it was reported that
      simultaneous expression of MATa and MATa genes in haploid cells of Saccharomyces
      cerevisiae increases microtubule stability [Mol. Gen. Genet. 264 (2000) 300]. In
      order to investigate the effect of zygosity in the MAT loci on microtubules
      independent of the effect of the actual ploidy, we compared microtubule stability
      and function in homozygous (MATa/MATa) and heterozygous (MATa/MATa) wild-type
      diploid cells. It was found that homozygosity in the MAT locus decreases
      stability of both cytoplasmic and nuclear microtubules. This was expressed in a
      more symmetrical distribution in the placement of the spindle relative to the
      neck, a delay in cytokinesis and reduced fidelity of chromosome segregation in
      these cells compared to the heterozygotes. Our results suggest that expression of
      both MAT loci initiates a pathway that results in an increase in microtubule
      stability and the fidelity of chromosome segregation in diploids. This pathway is
      independent of the pathway that determines the budding pattern in haploids and
      diploids, which is also initiated by simultaneous expression of MATa and MATa
      genes.

PMID- 12206655
TI  - The mitotic spindle and associated membranes in the closed mitosis of
      trichomonads.
AB  - In the present work, we followed the several phases of Tritrichomonas foetus and
      Trichomonas vaginalis cell cycles using immunofluorescence, serial thin sections,
      three-dimensional (3D) reconstruction, and transmission electron microscopy. In
      motile trichomonad cells or in pseudocyst forms, the nuclear envelope persists
      throughout mitosis, and the spindle is extranuclear. We found three types of
      spindle microtubules: pole-to-nucleus microtubules which are attached to the
      nuclear envelope, pole-to-pole microtubules forming a cylindrical, cytoplasmic
      groove on the nuclear compartment in pseudocysts of T. foetus cells, and pole-to
      cytosol microtubules which extend freely into the cytoplasm. We demonstrated
      that: (1) in T. foetus, the spindle is assembled from an MTOC located at the base
      of the costa, underneath one of the basal bodies; (2) the spindle presents an
      unusual arc shape during the initial phases of mitosis in motile trophozoites;
      (3) the spindle microtubules are glutamylated, but not acetylated; (4) several
      membranes similar to those of the endoplasmic reticulum follow the spindle
      microtubules; (5) finger-like projections extend from the nucleus towards the
      cell poles in pseudocysts and multinucleated cells; and (6) vesicles formed in
      between the two nuclear membranes are seen in the course of mitosis in both
      trophozoite and pseudocyst forms.

PMID- 12206656
TI  - Endocytic prolactin routes to the secretory pathway in lactating mammary
      epithelial cells.
AB  - Plasma-borne prolactin is carried from blood to milk by transcytosis across the
      mammary epithelial cell through the endocytic and secretory pathways. To
      determine the precise route of prolactin endocytosis, intracellular transport of
      biotinylated prolactin was monitored, in parallel with endocytosis of fluorescein
      isothiocyanate-conjugated dextran and IgG, by using pulse-chase experiments in
      lactating mammary fragments and in enzymatically dissociated acini. Biotinylated
      prolactin was sorted to vesiculo-tubular organelles whereas dextran was very
      rapidly carried to the lumen and IgG remained accumulated in the basal region of
      cells. To determine whether prolactin uses routes into and across the Golgi and
      trans-Golgi network, localisation of biotinylated prolactin was combined with the
      immunofluorescence detection of caseins and, respectively, p58 and TGN38.
      Biotinylated prolactin strongly colocalised with caseins during a chase but not
      all or only very little with p58 and TGN38. To characterise the organelles
      involved in transcytosis, gold-labelled prolactin, experimentally accumulated in
      late endosomes and which recovered a normal transport, was localised by electron
      microscopy. In mammary fragments incubated at low temperature, and in mammary
      fragments from rats fed with a lipid-deprived diet, transport of gold-labelled
      prolactin was restored by increasing the temperature and by adding arachidonic
      acid, respectively. These data demonstrate that a sorting occurs very rapidly
      between prolactin, dextran and IgG. They suggest that prolactin may reach the
      biosynthetic pathway after direct fusion between multivesicular bodies and
      secretory vesicles.

PMID- 12206657
TI  - Structure-function relationships in the integument of Salamandra salamandra
      during ontogenetic development.
AB  - Morphological, cytological and transport properties of the integument of
      Salamandra salamandra were investigated during natural ontogenetic development,
      from birth to adult. Three stages were operationally defined: I, larvae, from
      birth to metamorphosis; II, metamorphosis (judged externally by the colour change
      and loss of the gills); and III, post-metamorphosis to adult. Pieces of skin were
      fixed at various stages for immunocytochemical examinations, and the electrical
      properties were investigated on parallel pieces. Distinct cellular changes take
      place in the skin during metamorphosis, and lectin (PNA, WGA and ConA) binding
      indicates profound changes in glycoprotein composition of cell membranes,
      following metamorphosis. Band 3 and carbonic anhydrase I (CA I) were confined to
      mitochondria-rich (MR)-like cells, and were detected only in the larval stage. CA
      II on the other hand, was detected both in MR-like and in MR cells following
      metamorphosis. The electrical studies show that the skin becomes more tight
      (transepithelial resistance increases) upon metamorphosis, followed by
      manifestation of amiloride-sensitive short-circuit current (I(SC)) indicating
      that functional Na+ uptake has been acquired. The skin of metamorphosed adults
      had no finite transepithelial Cl- conductance, and band 3 was not detected in its
      MR cells. The functional properties of MR-like and MR cells remain to be
      established.

PMID- 12206658
TI  - Extracellular matrix development during differentiation into adipocytes with a
      unique increase in type V and VI collagen.
AB  - In order to study how adipose conversion affects the extracellular environment,
      levels of extracellular matrix (ECM) proteins during differentiation were
      analyzed by 125I-labeled antibody binding to each specific primary antibody. When
      confluent bovine intramuscular preadipocytes (BIP) were stimulated with
      adipogenic medium, there was a significant accretion on the cell surface of type
      I-VI collagens, laminin and fibronectin, compared with undifferentiated cells.
      The deposition amount of ECM proteins had reached near maximal levels at an early
      stage of differentiation and lasted throughout the culture. However, the
      increasing manners were not all the same in these eight proteins. Type V and type
      VI collagen tended to show a transient decline after the rapid rise at the
      beginning of stimulation, and fibronectin instead, subsequently decreased.
      Further analysis by immunocytochemical staining showed that remodeling occurred
      in type V and VI collagen matrices during this period; extensive fibrillar
      networks seen at 10 d after stimulation were quite unlike that formed earlier.
      These specific increases and development of matrix during adipocyte
      differentiation imply some significance for organizing fat lobules in each ECM
      proteins, especially type V and VI collagens.

PMID- 12206659
TI  - Comparative models for human apolipoprotein A-I bound to lipid in discoidal high
      density lipoprotein particles.
AB  - We have constructed a series of models for apolipoprotein A-I (apo A-I) bound to
      discoidal high-density lipoprotein (HDL) particles, based upon the molecular belt
      model [Segrest, J. P., et al. (1999) J. Biol. Chem. 274, 31755-31758] and helical
      hairpin models [Rogers, D. P., et al. (1998) Biochemistry 37, 11714-11725], and
      compared these with picket fence models [Phillips, J. C., et al. (1997) Biophys.
      J. 73, 2337-2346]. Molecular belt models for discoidal HDL particles with
      differing diameters are presented, illustrating that the belt model can explain
      the discrete changes in HDL particle size observed experimentally. Hairpin models
      are discussed for the binding of apo A-I to discoidal HDL particles with
      diameters identical to those for the molecular belt model. Two models are
      presented for the binding of three monomers of apo A-I to a 150 A diameter
      discoidal HDL particle. In one model, two monomers of apo A-I bind to the
      exterior of the HDL particle in an antiparallel belt, with a third monomer of apo
      A-I bound to the disk in a hairpin conformation. In the second model, all three
      monomers of apo A-I are bound to the discoidal HDL particle in a hairpin
      conformation. Previously published experimental data for each model are reviewed,
      with FRET favoring either the belt or hairpin models over the picket fence models
      for HDL particles with diameters of 105 A. Naturally occurring mutations appear
      to favor the belt model for the 105 A particles, while the 150 A HDL particles
      favor the presence of at least one hairpin.

PMID- 12206660
TI  - Identification of novel hemes generated by heme A synthase: evidence for two
      successive monooxygenase reactions.
AB  - Heme A, an obligatory cofactor in eukaryotic cytochrome c oxidase, is produced
      from heme B (protoheme) via two enzymatic reactions catalyzed by heme O synthase
      and heme A synthase. Heme O synthase is responsible for the addition of a
      farnesyl moiety, while heme A synthase catalyzes the oxidation of a methyl
      substituent to an aldehyde. We have cloned the heme O synthase and heme A
      synthase genes from Bacillus subtilis (ctaB and ctaA) and overexpressed them in
      Escherichia coli to probe the oxidative mechanism of heme A synthase. Because E.
      coli does not naturally produce or utilize heme A, this strategy effectively
      decoupled heme A biosynthesis from the native electron transfer pathway and heme
      A transport, allowing us to observe two previously unidentified hemes. We
      utilized HPLC, UV/visible spectroscopy, and tandem mass spectrometry to identify
      these novel hemes as derivatives of heme O containing an alcohol or a carboxylate
      moiety at position C8 on pyrrole ring D. We interpret these derivatives to be the
      putative alcohol intermediate and an overoxidized byproduct of heme A synthase.
      Because we have shown that all hemes produced by heme A synthase require O(2) for
      their synthesis, we propose that heme A synthase catalyzes the oxidation of the
      C8 methyl to an aldehyde group via two discrete monooxygenase reactions.

PMID- 12206661
TI  - Structural basis of phospholipase A2 inhibition for the synthesis of
      prostaglandins by the plant alkaloid aristolochic acid from a 1.7 A crystal
      structure.
AB  - This is the first structural observation of a plant product showing high affinity
      for phospholipase A(2) and regulating the synthesis of arachidonic acid, an
      intermediate in the production of prostaglandins. The crystal structure of a
      complex formed between Vipera russelli phospholipase A(2) and a plant alkaloid
      aristolochic acid has been determined and refined to 1.7 A resolution. The
      structure contains two crystallographically independent molecules of
      phospholipase A(2) in the form of an asymmetric dimer with one molecule of
      aristolochic acid bound to one of them specifically. The most significant
      differences introduced by asymmetric molecular association in the structures of
      two molecules pertain to the conformations of their calcium binding loops, beta
      wings, and the C-terminal regions. These differences are associated with a unique
      conformational behavior of Trp(31). Trp(31) is located at the entrance of the
      characteristic hydrophobic channel which works as a passage to the active site
      residues in the enzyme. In the case of molecule A, Trp(31) is found at the
      interface of two molecules and it forms a number of hydrophobic interactions with
      the residues of molecule B. Consequently, it is pulled outwardly, leaving the
      mouth of the hydrophobic channel wide open. On the other hand, Trp(31) in
      molecule B is exposed to the surface and moves inwardly due to the polar
      environment on the molecular surface, thus narrowing the opening of the
      hydrophobic channel. As a result, the aristolochic acid is bound to molecule A
      only while the binding site of molecule B is empty. It is noteworthy that the
      most critical interactions in the binding of aristolochic acid are provided by
      its OH group which forms two hydrogen bonds, one each with His(48) and Asp(49).

PMID- 12206662
TI  - Kinetic characterization of native and cysteine 112-modified glutathione S
      transferase A1-1: reassessment of nonsubstrate ligand binding.
AB  - We have prepared human glutathione S-transferase isoform A1-1 (GST A1-1) which
      has been chemically modified at cysteine 112. These modifications include
      formation of mixed disulfides with glutathione ("glutathiolation") and cross
      linkage of the GST dimer with bis-maleimides reacting with the equivalent Cys 112
      residues of the two monomers. This residue (Cys 112) lies adjacent to the
      hydrophobic substrate binding site, and its side chain thiol projects into the
      large, solvent-filled cleft which is widely reported in the literature to be the
      binding site of nonsubstrate ligands. Both types of modification block this
      intersubunit cleft region and significantly change its chemical environment.
      Kinetic experiments with these altered enzymes revealed that neither type of
      modification affects the catalytic activity of GST A1-1 or the binding of
      nonsubstrate ligands. The lack of an effect on glutathione conjugation activity
      is somewhat surprising given the proximity of cysteine 112 to the hydrophobic
      substrate binding site. More surprising, however, is the observation that
      modification at cysteine 112 has no effect on the binding of nonsubstrate
      ligands. Furthermore, two of these ligands, lithocholic acid and estradiol
      disulfate, unexpectedly exhibited competitive inhibition of the unmodified
      enzyme, suggesting that they bind in the hydrophobic substrate site rather than
      some accessory ligand binding site. Together, these results strongly argue
      against the intersubunit cleft as the nonsubstrate ligand binding site and prompt
      a reassessment of how these ligands interact with GST A1-1.

PMID- 12206663
TI  - Membrane topologies of neuronal SNARE folding intermediates.
AB  - Assembly of the SNARE complex is essential for neurotransmitter release at
      synapses. Target plasma membrane SNAREs (t-SNAREs) syntaxin 1A and SNAP-25 form
      the t-SNARE complex that serves as an intermediate toward final SNARE assembly
      with vesicle-associated SNARE (v-SNARE). Membrane topologies of syntaxin 1A and
      the t-SNARE complex were investigated using site-directed spin labeling EPR. EPR
      analysis revealed that the basic region at the membrane-water interface is
      unstructured but inserted into the membrane. Such membrane insertion leaves no
      gap between the t-SNARE core and the membrane. Yet the lack of structure could
      provide the flexibility necessary for the t-SNARE core. Further, the insertion of
      the basic interfacial region into the membrane may have profound implications for
      the mechanism of SNARE-induced membrane fusion.

PMID- 12206664
TI  - Biochemical evidence for multiple dimeric states of the Sinorhizobium meliloti
      DctD receiver domain.
AB  - X-ray crystal structures suggest very different dimeric states for the inactive
      and active forms of the two-component receiver domain of Sinorhizobium meliloti
      DctD, a sigma(54)-dependent AAA+ ATPase. Moreover, the receiver domain in
      crystals grown from unphosphorylated protein is refractory to phosphorylation
      whereas solution protein is fully phosphorylatable, and equilibrium analytical
      ultracentrifugation data are consistent with solution dimers for both
      phosphorylated and unphosphorylated forms of the protein. Here we report
      biochemical data consistent with the presence of multiple dimeric conformations
      in the inactive and active states, and evidence for significant change in the
      dimeric state upon activation by phosphorylation or binding of Mg(2+) and BeF(3)(
      ).

PMID- 12206665
TI  - Solution structure and backbone dynamics of the functional cytoplasmic subdomain
      of human ephrin B2, a cell-surface ligand with bidirectional signaling
      properties.
AB  - The cytoplasmic domain of B ephrins plays a central role in bidirectional signal
      transduction processes controlling pattern formation and morphogenesis, such as
      axon guidance, cell migration, segmentation, and angiogensis. In particular, the
      extremely conserved last 33-residue cytoplasmic subdomain was shown to bind to
      both a PDZ domain for one signaling pathway [Lu et al. (2001) Cell 105, 69-79]
      and an SH2 domain from an alternative signaling network [Cowan and Henkemeyer
      (2001) Nature 413, 174-179]. To date, no structural information is available for
      the cytoplasmic domain of ephrin B proteins. We report here a detailed NMR study
      on the structural and dynamic properties of the cytoplasmic domain of human
      ephrin B2. Our results reveal the following: (1) the N-terminal region of the
      cytoplasmic domain from residues 253 to 300 lacks the ability for structure
      formation and is particularly prone to aggregation; and (2) the C-terminal
      functional subdomain from residues 301 to 333 assumes two distinctive structural
      elements with residues 301-322 adopting a well-packed hairpin structure followed
      by a flexible C-terminal tail. Furthermore, the backbone (15)N relaxation data
      demonstrate that the hairpin structure has significantly limited backbone
      motions, indicating a high conformational stability for the folded structure.
      Therefore, while the flexible C-terminal tail is suitable for binding to the PDZ
      domain, the folded hairpin may represent a latent structure requiring
      phosphorylation-induced conformational changes for high-affinity interactions
      with the SH2 domain.

PMID- 12206666
TI  - Crystallographic investigation of the role of aspartate 95 in the modulation of
      the redox potentials of Desulfovibrio vulgaris flavodoxin.
AB  - The side chain of aspartate 95 in flavodoxin from Desulfovibrio vulgaris provides
      the closest negative charge to N(1) of the bound FMN in the protein. Site
      directed mutagenesis was used to substitute alanine, asparagine, or glutamate for
      this amino acid to assess the effect of this charge on the
      semiquinone/hydroquinone redox potential (E(1)) of the FMN cofactor. The D95A
      mutation shifts the E(1) redox potential positively by 16 mV, while a negative
      shift of 23 mV occurs in the oxidized/semiquinone midpoint redox potential
      (E(2)). The crystal structures of the oxidized and semiquinone forms of this
      mutant are similar to the corresponding states of the wild-type protein. In
      contrast to the wild-type protein, a further change in structure occurs in the
      D95A mutant in the hydroquinone form. The side chain of Y98 flips into an
      energetically more favorable edge-to-face interaction with the bound FMN.
      Analysis of the structural changes in the D95A mutant, taking into account
      electrostatic interactions at the FMN binding site, suggests that the pi-pi
      electrostatic repulsions have only a minor contribution to the very low E(1)
      redox potential of the FMN cofactor when bound to apoflavodoxin. Substitution of
      D95 with glutamate causes only a slight perturbation of the two one-electron
      redox potentials of the FMN cofactor. The structure of the D95E mutant reveals a
      large movement of the 60-loop (residues 60-64) away from the flavin in the
      oxidized structure. Reduction of this mutant to the hydroquinone causes the
      conformation of the 60-loop to revert back to that occurring in the structures of
      the wild-type protein. The crystal structures of the D95E mutant imply that
      electrostatic repulsion between a carboxylate on the side chain at position 95
      and the phenol ring of Y98 prevents rotation of the Y98 side chain to a more
      energetically favorable conformation as occurs in the D95A mutant. Replacement of
      D95 with asparagine has no effect on E(2) but causes E(1) to change by 45 mV. The
      D95N mutant failed to crystallize. The K(d) values of the protein FMN complex in
      all three oxidation-reduction states differ from those of the wild-type
      complexes. Molecular modeling showed that the conformational energy of the
      protein changes with the redox state, in qualitative agreement with the observed
      changes in K(d), and allowed the electrostatic interactions between the FMN and
      the surrounding groups on the protein to be quantified.

PMID- 12206667
TI  - Crystal structure of memapsin 2 (beta-secretase) in complex with an inhibitor
      OM00-3.
AB  - The structure of the catalytic domain of human memapsin 2 bound to an inhibitor
      OM00-3 (Glu-Leu-Asp-LeuAla-Val-Glu-Phe, K(i) = 0.3 nM, the asterisk denotes the
      hydroxyethylene transition-state isostere) has been determined at 2.1 A
      resolution. Uniquely defined in the structure are the locations of S(3)' and
      S(4)' subsites, which were not identified in the previous structure of memapsin 2
      in complex with the inhibitor OM99-2 (Glu-Val-Asn-LeuAla-Ala-Glu-Phe, K(i) = 1
      nM). Different binding modes for the P(2) and P(4) side chains are also observed.
      These new structural elements are useful for the design of new inhibitors. The
      structural and kinetic data indicate that the replacement of the P(2)' alanine in
      OM99-2 with a valine in OM00-3 stabilizes the binding of P(3)' and P(4)'.

PMID- 12206668
TI  - Mutations in the ribonuclease H active site of HIV-RT reveal a role for this site
      in stabilizing enzyme-primer-template binding.
AB  - The RNase H activity of HIV-RT is coordinated by a catalytic triad (E478, D443,
      D498) of acidic residues that bind divalent cations. We examined the effect of
      RNase H deficient E(478)-->Q and D(549)-->N mutations that do not alter
      polymerase activity on binding of enzyme to various nucleic acid substrates.
      Binding of the mutant and wild-type enzymes to various nucleic acid substrates
      was examined by determining dissociation rate constants (k(off)) by titrating
      both Mg(2+) and salt concentrations. In agreement with the unaltered polymerase
      activity of the mutant, the k(off) values for the wild-type and mutant enzymes
      were essentially identical using DNA-DNA templates in the presence of 6 mM
      Mg(2+). However, with lower concentrations of Mg(2+) and in the absence of
      Mg(2+), although both enzymes dissociated more rapidly, the mutant enzymes
      dissociated several-fold more slowly than the wild type. This was also observed
      on RNA-DNA templates. These results indicate that alterations in residues
      essential for Mg(2+) binding have a pronounced positive effect on enzyme-template
      stability and that the negative residues in the RNase H region of the enzyme have
      a negative influence on binding in the absence of Mg(2+). In this regard RT is
      similar to other nucleic acid cleaving enzymes that show enhanced binding upon
      mutation of active site residues.

PMID- 12206669
TI  - Role of DNA flexibility in sequence-dependent activity of uracil DNA glycosylase.
AB  - Uracil DNA glycosylase (UDG) is a base excision repair enzyme that specifically
      recognizes and removes uracil from double- or single-stranded DNA. The efficiency
      of the enzyme depends on the DNA sequence surrounding the uracil. Crystal
      structures of UDG in complex with DNA reveal that the DNA is severely bent and
      distorted in the region of the uracil. This suggests that the sequence-dependent
      efficiency of the enzyme may be related to the energetic cost of DNA distortion
      in the process of specific damage recognition. To test this hypothesis, molecular
      dynamics simulations were performed on two sequences representing extreme cases
      of UDG efficiency, AUA/TAT (high efficiency) and GUG/CAC (low efficiency).
      Analysis of the simulations shows that the effective bending force constants are
      lower for the AUA/TAT sequence, indicating that this sequence is more flexible
      than the GUG/CAC sequence. Fluorescence lifetimes of the adenine analogue 2
      aminopurine (2AP), replacing adenine opposite the uracil, are shorter in the
      context of the AUA/TAT sequence, indicating more dynamic base-base interaction
      and greater local flexibility than in the GUG/CAC sequence. Furthermore, the K(M)
      of Escherichia coli UDG for the AUA/TAT sequence is 10-fold smaller than that for
      the GUG/CAC sequence, while the k(cat) is only 2-fold smaller. This indicates
      that differences in UDG efficiency largely arise from differences in binding and
      not catalysis. These results link directly flexibility near the damaged DNA site
      with the efficiency of DNA repair.

PMID- 12206670
TI  - Parallel symmetric immobile DNA junctions as substrates for E. coli RuvC Holliday
      junction resolvase.
AB  - RuvC is a well-characterized Holliday junction resolvase from E. coli. The
      presence of symmetry in its preferred recognition sequence leads to ambiguity in
      the position of the crossover point in the junction, because a symmetric junction
      can undergo branch migration. Symmetric immobile junctions are junctions that
      contain such symmetric sites, but are prevented from migrating by their physical
      characteristics. RuvC activity had been analyzed previously by traditional
      symmetric immobile junctions, in which the helix axes are held antiparallel in a
      double-crossover motif. Bowtie junctions are branched four-arm molecules
      containing 5',5' and 3',3' linkages at their crossover points. A new type of
      symmetric immobile junction can be made by flanking the crossover point of a
      Bowtie junction with a symmetric sequence. The junction is immobile because
      mobility would lead to pairing between parallel, rather than antiparallel,
      nucleotide pairs. In contrast to conventional Holliday junctions and their
      analogues, the Bowtie junction assumes a parallel, rather than antiparallel,
      helical domain conformation, offering a new type of substrate for Holliday
      junction resolvases. Here, we report the digestion of Bowtie junctions by RuvC.
      We demonstrate that Bowtie junctions can function as symmetric immobile junctions
      in this system. We also show that RuvC cleaves antiparallel junctions much more
      efficiently than parallel junctions, where the protein can bind (and cleave) only
      one site at a time. These data suggest that the presence of two binding sites
      leads to communication between the two subunits of the enzyme to increase its
      activity.

PMID- 12206671
TI  - L-methionine inhibits reaction of DNA with anticancer cis
      diamminedichloroplatinum(II).
AB  - Sufficient evidence has accumulated to identify DNA as the relevant
      pharmacological target of antitumor cisplatin [cis-diamminedichloroplatinum(II)].
      This drug is administered intravenously so that before it reaches DNA in the
      nucleus of tumor cells it may interact with various compounds including sulfur
      containing molecules such as L-methionine or the compounds containing these
      residues. L-Methionine increases the rate of reaction of cisplatin with monomeric
      guanosine 5'-monophosphate, and it was suggested on the basis of these results
      previously obtained by other authors that methionine residues could mediate the
      transfer of platinum onto DNA. We studied in the present work the reactions of
      the 1:1 complex formed between cisplatin and L-methionine or N-acetyl-L
      methionine with synthetic, single- and double-stranded oligodeoxyribonucleotides
      and natural, high molecular mass DNA by using high-pressure liquid chromatography
      and flameless atomic absorption spectrophotometry. The results demonstrate that
      both L-methionine and N-acetyl-L-methionine decrease the rate of reaction of
      cisplatin with base residues in natural, high molecular mass DNA. Thus, the
      possibility that cisplatin bound to methionine residues serves as a drug
      reservoir available for platination of DNA in the nucleus of tumor cells appears
      unlikely.

PMID- 12206673
TI  - Unfolding and conformational studies on bovine adrenodoxin probed by engineered
      intrinsic tryptophan fluorescence.
AB  - An intrinsic steady-state fluorescent system for bovine adrenodoxin has been
      developed to study the protein structure in solution and the processes involved
      in protein unfolding. Since mature Adx contains no natural Trp residue as
      internal probe, all of the aromatic amino acids, tyrosine at position 82 and four
      phenylalanines at positions 11, 43, 59 and 64, were at each case replaced by
      tryptophan. The resulting single tryptophan containing mutants kept their
      biological function compared with the wild type. Molecular modeling studies
      verify thermal unfolding experiments which point to a dramatically reduced
      stability caused by steric hindrance only for mutant F59W. Fluorescence spectra,
      Stern-Volmer quenching constants, and fluorescence energy transfer calculations
      indicated the analyzed positions to be situated in solution in the same immediate
      environment as in the crystal structure. Unfolding experiments with Gdn-HCl and
      time-resolved stopped-flow measurements provide evidence for differential
      stability and a chronologically ordered unfolding mechanism of the different
      fluorescence probe positions in the protein.

PMID- 12206672
TI  - Inhibition of transforming growth factor-beta signaling by low molecular weight
      compounds interfering with ATP- or substrate-binding sites of the TGF beta type I
      receptor kinase.
AB  - Transforming growth factor-beta (TGFbeta) is a potent regulator of cell
      proliferation, differentiation, apoptosis, and migration. TGF-beta type I
      receptor (TbetaR-I), which has intrinsic serine/threonine kinase activity, is a
      key component in activation of intracellular TGFbeta signaling. We studied two
      different classes of TbetaR-I inhibitors, i.e., compounds interfering with the
      ATP-binding site of the kinase and substrate-mimicking peptides. We found that
      pyridinylimidazole compounds inhibited TbetaR-I kinase at micromolar
      concentration. A representative compound, SB203580, inhibited in vivo Smad2
      phosphorylation by TbetaR-I and affected TGFbeta-dependent transcriptional
      activation. Peptides mimicking the TbetaR-I phosphorylation sites at the C
      terminus of Smad2 also inhibited the autophosphorylation of TbetaR-I and
      phosphorylation of Smad2 by TbetaR-I in vitro and in vivo, whereas a similar
      peptide from Smad5 was without effect. The substrate-mimicking peptide, fused to
      penetratin, inhibited a TGFbeta1-dependent transcriptional response in a
      luciferase reporter assay and ligand-dependent growth inhibition of Mv1Lu cells.
      Thus, the substrate-mimetic peptide is a new type of specific inhibitor of the
      TGFbeta signaling in vivo.

PMID- 12206674
TI  - Unusual property of prion protein unfolding in neutral salt solution.
AB  - The unfolding of cellular prion protein and its refolding to the scrapie isoform
      are related to prion diseases. Studies in the literature have shown that
      structures of proteins, either acidic or basic, are stabilized against
      denaturation by certain neutral salts, for example, sulfate and fluoride.
      Contrary to these observations, the full-length recombinant prion protein (amino
      acid residues 23-231) is denatured by these protein structure stabilizing salts.
      Under identical concentrations of salts, the structure of the sheep prion
      protein, which contains a greater number of glycine groups in the N-terminal
      unstructured segment than the mouse protein, becomes more destabilized. In
      contrast to the full-length protein, the C-terminal 121-231 prion protein
      fragment, consisting of all the structural elements of the protein, viz., three
      alpha-helices and two short beta-strands, is stabilized against denaturation by
      these salts. We suggest that an increase in the concentration of the anions on
      the surface of the prion protein molecule due to their preferential interaction
      with the glycine residues in the N-terminal segment destabilizes the structure of
      the prion protein by perturbing the prion helix 1 which is the most soluble of
      all the protein alpha-helices reported so far in the literature. The present
      results could be relevant to explain the observed structural conversion of the
      prion protein by anionic nucleic acids and sulfated glycosaminoglycans.

PMID- 12206675
TI  - Diversity in the oxidation of substrates by cytochrome P450 2D6: lack of an
      obligatory role of aspartate 301-substrate electrostatic bonding.
AB  - Cytochrome P450 (P450) 2D6 was first identified as the polymorphic human
      debrisoquine hydroxylase and subsequently shown to catalyze the oxidation of a
      variety of drugs containing a basic nitrogen. Residue Asp301 has been
      characterized as being involved in electrostatic interactions with substrates on
      the basis of homology modeling and site-directed mutagenesis experiments [Ellis,
      S. W., Hayhurst, G. P., Smith, G., Lightfoot, T., Wong, M. M. S., Simula, A. P.,
      Ackland, M. J., Sternberg, M. J. E., Lennard, M. S., Tucker, G. T., and Wolf, C.
      R. (1995) J. Biol. Chem. 270, 29055-29058]. However, pharmacophore models based
      on the role of Asp301 in substrate binding are compromised by reports of
      catalytic activity toward substrates devoid of a basic nitrogen, which have
      generally been ignored. We characterized a high-affinity ligand for P450 2D6,
      also devoid of a basic nitrogen atom, spirosulfonamide [4-[3-(4-fluorophenyl)-2
      oxo-1-oxaspiro[4.4]non-3-en-4-yl]benzenesulfonamide], with K(s) 1.6 microM.
      Spirosulfonamide is a substrate for P450 2D6 (k(cat) 6.5 min(-)(1) for the
      formation of a syn spiromethylene carbinol, K(m) 7 microM). Mutation of Asp301 to
      neutral residues (Asn, Ser, Gly) did not substantially affect the binding of
      spirosulfonamide (K(s) 2.5-3.5 microM). However, the hydroxylation of
      spirosulfonamide was attenuated in these mutants to the same extent (90%) as for
      the classic nitrogenous substrate bufuralol, and the effect of the D301N
      substitution was manifested on k(cat) but not K(m). Analogues of spirosulfonamide
      were also evaluated as ligands and substrates. Analogues in which the sulfonamide
      moiety was modified to an amide, thioamide, methyl sulfone, or hydrogen were
      ligands with K(s) values of 1.7-32 microM. All were substrates, and the methyl
      sulfone analogue was oxidized to the syn spiromethylene carbinol analogue of the
      major spirosulfonamide product. The D301N mutation produced varying changes in
      the oxidation patterns of the spirosulfonamide analogues. The peptidometic
      ritonavir and the steroids progesterone and testosterone had been reported to be
      substrates for P450 2D6, but the affinities (K(s)) were unknown; these were
      estimated to be 1.2, 1.5, and 15 microM, respectively (cf. 6 microM for the
      classic substrate bufuralol). The results are consistent with a role of Asp301
      other than electrostatic interaction with a positively charged ligand. H-Bonding
      or electrostatic interactions probably enhance binding of some substrates, but
      our results show that it is not required for all substrates and explain why
      predictive models fail to recognize the proclivity for many substrates,
      especially those containing no basic nitrogen.

PMID- 12206676
TI  - Photoexcitation of tryptophan groups induces reduction of two disulfide bonds in
      goat alpha-lactalbumin.
AB  - Illumination of goat alpha-lactalbumin (GLA) with 280 or 295 nm light results in
      tryptophan-mediated photolysis of disulfide bonds within the protein. The
      photolysis is not dependent on the absence or presence of Ca(2+) and is observed
      as well on illumination of native and of partially unfolded GLA. However,
      photolysis of native GLA results in a partial unfolding of the protein. The
      latter phenomenon is most clearly observed on fluorescence measurements at low
      temperatures (near 3 degrees C). The photolysis induces some dimerization and
      oligomerization, but most GLA molecules remain monomeric. To obtain more
      information about the reaction products, the illuminated protein is treated with
      iodoacetamide to label the free thiol groups, it is fragmented with trypsin, and
      the fragments are analyzed by mass spectrometry. Via this approach, we observe
      that the cleavage of disulfide bonds is restricted to Cys6-Cys120 and Cys73-Cys91
      bonds. The photolytic cleavage of either of these disulfide bonds results in the
      formation of a single free thiol, a phenomenon restricted to Cys120 and Cys91,
      respectively. We also found indications that a thioether linkage is formed
      between Cys73 and Trp60. The alkylsulfenylation of Trp60 presumably results from
      a combination of primary thiyl and tryptyl radicals.

PMID- 12206677
TI  - Mechanism and kinetics of delta-lysin interaction with phospholipid vesicles.
AB  - Delta-lysin is a 26 amino acid, hemolytic peptide toxin secreted by
      Staphylococcus aureus. It has been reported to form an amphipathic helix upon
      binding to lipid bilayers and is often cited as a typical example of the barrel
      stave model for pore formation in lipid bilayer membranes. However, the exact
      mechanism by which it lyses cells and the physical basis of its target
      specificity are still unknown. Moreover, the evidence for delta-lysin insertion
      and pore formation in the membrane stems largely from theoretical modeling of the
      toxin and lacks experimental confirmation. We investigated binding and insertion
      of delta-lysin into phospholipid bilayer vesicles. The kinetics of these
      processes were studied by stopped-flow fluorescence with two types of
      experiments: (a) carboxyfluorescein release from the vesicles upon peptide
      vesicle interaction, with concomitant relief of dye self-quenching; (b)
      fluorescence energy transfer from the intrinsic tryptophan of the peptide to a
      membrane-bound lipid probe. We formulated a detailed kinetic mechanism with
      explicit molecular rate constants for peptide binding, association, and
      insertion, obtaining a quantitative description of the experimental results.
      delta-Lysin insertion is strongly dependent on the peptide-to-lipid ratio,
      suggesting that association of a critical number of monomers on the membrane is
      required for activity. However, we found no evidence for a stable membrane
      inserted pore. Rather, the peptide appears to cross the membrane rapidly and
      reversibly and cause release of the lipid vesicle contents in this process.

PMID- 12206679
TI  - pH-controlled fluorescent emission in the nickel(II) complex of a bifunctional
      tetramine macrocycle.
AB  - In the Ni(II) complex of a reinforced tetramine macrocycle, equipped with both a
      sulfonamide pendant arm and a naphthalene fragment, light emission of the
      fluorophore is pH-controlled, as a result of a change of the geometry of the
      complex.

PMID- 12206678
TI  - Repair of amino acid radicals of apolipoprotein B100 of low-density lipoproteins
      by flavonoids. A pulse radiolysis study with quercetin and rutin.
AB  - Selective oxidative damage to apolipoprotein B in LDL can be effected
      radiolytically by (*)Br(2)(-) radicals. Twenty-seven Trp residues constitute
      major primary sites of oxidation, but two-thirds of oxidized Trps ((*)Trp) that
      are formed are repaired by intramolecular electron transfer from Tyr residues
      with formation of phenoxyl radicals (TyrO(*)). Analysis of (*)Trp and TyrO(*)
      transient absorbance changes suggests that other apolipoprotein B residues,
      probably Cys, are oxidized. LDL-bound quercetin can efficiently repair this
      damage. Absorption studies show that a LDL particle has the capacity to bind
      approximately 10 quercetin molecules through interaction with apolipoprotein B.
      The repair occurs by intramolecular electron transfer characterized by a rate
      constant of 2 x 10(3) s(-)(1). In contrast, rutin, a related flavonoid which does
      not bind to LDL, cannot repair oxidized apolipoprotein B. Urate is a hydrophilic
      plasma antioxidant which displays synergistic antioxidant properties with
      flavonoids. Urate radicals produced by (*)Br(2)(-) can also be repaired by LDL
      bound quercetin. This repair occurs with a reaction rate constant of 6.8 x 10(7)
      M(-)(1) s(-)(1). Comparison with previous studies conducted with human serum
      albumin-bound quercetin suggests that quercetin analogues tailored to be carried
      preferentially by lipoproteins might be more powerful plasma antioxidants than
      natural quercetin carried by serum albumin.

PMID- 12206680
TI  - Ferromagnetism and chirality in two-dimensional cyanide-bridged bimetallic
      compounds.
AB  - The combination of hexacyanoferrate(III) anions, [Fe(CN)(6)](3)(-), with
      nickel(II) complexes derived from the chiral ligand trans-cyclohexane-1,2-diamine
      (trans-chxn) affords the enantiopure layered compounds [Ni(trans-(1S,2S)
      chxn)(2)](3)[Fe(CN)(6)](2).2H(2)O (1) and [Ni(trans-(1R,2R)
      chxn)(2)](3)[Fe(CN)(6)](2).2H(2)O (2). These chiral systems behave as
      ferromagnets (T(c) = 13.8 K) with a relatively high coercive field (H(c) = 0.17
      T) at 2 K. They also exhibit an unusual magnetic behavior at low temperatures
      that has been attributed to the dynamics of the magnetic domains in the ordered
      phase.

PMID- 12206681
TI  - X-ray crystal structure of (eta(5)-pentaphenylcyclopentadienyl)[1-(eta(5/6)
      phenyl)-2,3,4,5-tetraphenylcyclopentadienyl]iron(II), [Fe(eta(5)
      C(5)Ph(5))[(eta(5/6)-C(6)H(5))C(5)Ph(4)]], a linkage isomer of
      decaphenylferrocene.
AB  - Very dark blue prismatic crystals of [Fe(eta(5)-C(5)Ph(5))[(eta(5/6)
      C(6)H(5))(C(5)Ph(4))]], the linkage isomer of decaphenylferrocene, were grown
      from (3:1 v/v) hexane/ethyl acetate and characterized by single-crystal X-ray
      diffraction (space group P2(1)/n, R1(F) 0.0404). The iron atom is coordinated to
      two C(5)Ph(5) ligands: one with an eta(5)-C(5)-configuration and the other with a
      coordinated arene configuration. The phenyl groups of the (eta(5)-C(5)Ph(5))
      ligand are oriented in a "paddle-wheel" arrangement about the C(5) ring, with
      which four of them make an average angle of approximately 53 degrees, the other,
      an angle of approximately 42 degrees. The coordinated C(6)H(5) ring of the other
      ligand is inclined at only approximately 5 degrees to the uncoordinated C(5)
      ring, with which three of the other four phenyl rings make an average angle of
      approximately 64 degrees, and the other (opposite the coordinated arene ring), an
      angle of 38 degrees.

PMID- 12206682
TI  - Hydrothermal synthesis of the first vanadomolybdenum polyoxocation with a "metal
      bonded" spherical framework.
AB  - The heteropoly compound [(V(V)O(4))Mo(VI)(12)O(36)(V(IV)O)(6)][(OH)(9)].11H(2)O
      (1), synthesized by hydrothermal method under weak basic conditions, represents
      the first mixed Mo/V six-capped Keggin structural derivative with a spherical
      skeleton, and the first transition metal polyoxocation. The successful synthesis
      of 1 demonstrates that basic hydrothermal synthesis might be a power synthetic
      route to the isolation of more new polycationic metal-oxo clusters.

PMID- 12206683
TI  - Synthesis, structure, properties, and phosphatase-like activity of the first
      heterodinuclear Fe(III)Mn(II) complex with the unsymmetric ligand H(2)BPBPMP as a
      model for the PAP in sweet potato.
AB  - The new heterodinuclear mixed valence complex
      [Fe(III)Mn(II)(BPBPMP)(OAc)(2)]ClO(4) (1) with the unsymmetrical N(5)O(2) donor
      ligand 2-bis[((2-pyridylmethyl)-aminomethyl)-6-((2-hydroxybenzyl)(2
      pyridylmethyl))-aminomethyl]-4-methylphenol (H(2)BPBPMP) has been synthesized and
      characterized. Compound 1 crystallizes in the monoclinic system, space group
      P2(1)/c, and has an Fe(III)Mn(II)(mu-phenoxo)-bis(mu-carboxylato) core. Two
      quasireversible electron transfers at -870 and +440 mV versus Fc/Fc(+)
      corresponding to the Fe(II)Mn(II)/Fe(III)Mn(II) and Fe(III)Mn(II)/Fe(III)Mn(III)
      couples, respectively, appear in the cyclic voltammogram. The dinuclear
      Fe(III)Mn(II) center has weakly antiferromagnetic coupling with J = -6.8 cm(-1)
      and g = 1.93. The (57)Fe Mossbauer spectrum exhibits a single doublet, delta =
      0.48 mm s(-1) and DeltaE(Q) = 1.04 mm s(-1) for the high spin Fe(III) ion.
      Phosphatase-like activity at pH 6.7 with the substrate 2,4
      bis(dinitrophenyl)phosphate reveals saturation kinetics with the following
      Michaelis-Menten constants: K(m) = 2.103 mM, V(max) = 1.803 x 10(-5) mM s(-1),
      and k(cat) = 4.51 x 10(-4) s(-1).

PMID- 12206684
TI  - Molecular structures of five-coordinated halide ligated iron(III) porphyrin,
      porphycene, and corrphycene complexes.
AB  - Molecular structures of 12 porphyrin analogues, Fe(III)(EtioP)X(1(a)-1(d)),
      Fe(III)(EtioCn)X(2(a)-2(d)), and Fe(III)(Etio-Pc)X(3(a)-3(d)), where X = F (a),
      Cl (b), Br (c), and I (d), are determined on the basis of X-ray crystallography.
      Combined analyses using Mossbauer, (1)H NMR, and EPR spectroscopy as well as
      SQUID magnetometry have revealed that 3(d) exhibits a quite pure S = 3/2 spin
      state with a small amount of an S = 5/2 spin admixture. In contrast, all the
      other complexes show the S = 5/2 spin state with a small amount of the S = 3/2
      spin admixture. The structural and spectroscopic data indicate a strong
      correlation between the spin states of the complexes and the core geometries such
      as Fe-N bond lengths, cavity areas, and DeltaFe values.

PMID- 12206685
TI  - Possible nonactivated conductivity of the low-dimensional ternary nitride
      Ca(2)GeN(2).
AB  - The electronic structure of the recently reported ternary nitride Ca(2)GeN(2) has
      been studied by means of first-principles density functional calculations. The
      relatively short nonbonded Ge...Ge contacts along the direction approximately
      perpendicular to the plane of the bent GeN(2) units confer a large dispersion to
      the energy bands based on the antibonding pi-type level of GeN(2). This feature
      as well as the smaller but non-negligible interactions along the perpendicular
      directions suggests that this material, despite being built from discrete units,
      may exhibit a metallic behavior. This study suggests that the nature of the
      alkaline-earth atom has a crucial influence on the electrical conductivity of
      this type of phase.

PMID- 12206686
TI  - A periodic walk: a series of first-row transition metal complexes with the
      pentadentate ligand PY5.
AB  - A series of transition metal complexes derived from the pentadentate ligand PY5,
      2,6-(bis-(bis-2-pyridyl)methoxymethane)pyridine, illustrates the intrinsic
      propensity of this ligand to complex metal ions. X-ray structural data are
      provided for six complexes (1-6) with cations of the general formula
      [M(II)(PY5)(Cl)](+), where M = Mn, Fe, Co, Ni, Cu, Zn. In complexes 1-4 and 6,
      the metal ions are coordinated in a distorted-octahedral fashion; the four
      terminal pyridines of PY5 occupy the equatorial sites while the axial positions
      are occupied by the bridging pyridine of PY5 and a chloride anion. Major
      distortions from an ideal octahedral geometry arise from displacement of the
      metal atom from the equatorial plane toward the chloride ligand and from
      differences in pyridine-metal-pyridine bond angles. The series of complexes shows
      that M(II) ions are consistently accommodated in the ligand by displacement of
      the metal ion from the PY5 pocket, a tilting of the axial pyridine subunit, and
      nonsymmetrical pyridine subunit ligation in the equatorial plane. The
      displacement from the ligand pocket increases with the ionic radius of M(II). The
      axial pyridine tilt, however, is approximately the same for all complexes and
      appears to be independent of the electronic ground state of M(II). In complex 5,
      the Cu(II) ion is coordinated by only four of the five pyridine subunits of the
      ligand, resulting in a square-pyramidal complex. The overall structural
      similarity of 5 with the other complexes reflects the strong tendency of PY5 to
      enforce a distorted-octahedral coordination geometry. Complexes 1-6 are further
      characterized in terms of solution magnetic susceptibility, electrochemical
      behavior, and optical properties. These show the high-spin nature of the
      complexes and the anticipated stabilization of the divalent oxidation state.

PMID- 12206687
TI  - A spectrochemical walk: single-site perturbation within a series of six
      coordinate ferrous complexes.
AB  - A series of ferrous complexes with the pentadentate ligand 2,6-(bis-(bis-2
      pyridyl)methoxymethane)pyridine (PY5) was prepared and examined. PY5 binds
      ferrous iron in a square-pyramidal geometry, leaving a single coordination site
      accessible for complexation of a wide range of monodentate exogenous ligands:
      [Fe(II)(PY5)(X)](n+), X = MeOH, H(2)O, MeCN, pyridine, Cl-, OBz-, N(3)-, MeO-,
      PhO-, and CN-. The spin-states of these ferrous complexes are extremely sensitive
      to the nature of the single exogenous ligand; the spectroscopic and structural
      properties correlate with their high-spin (hs) or low-spin (ls) electronic ground
      state. Systematic metrical trends within six crystallographic structures clearly
      indicate a preferred conformational binding mode of the PY5 ligand. The relative
      binding affinities of the exogenous ligands in MeOH indicate that exogenous
      ligand charge is the primary determinant of the binding affinity; the
      [Fe(II)(PY5)](2+) unit preferentially binds anionic ligands over neutral ligands.
      At parity of charge, strong-field ligands are preferentially bound over weak
      field ligands. In MeOH, the pK(a) of the exogenously ligated MeOH in
      [Fe(PY5)(MeOH)](2+) (9.1) limits the scope of exogenous ligands, as strongly
      basic ligands preferentially deprotonate [Fe(PY5)(MeOH)](2+) to yield
      [Fe(PY5)(OMe)](1+) rather than ligate to the ferrous center. Exogenous ligation
      by a strongly basic ligand, however, can be achieved in polar aprotic solvents.

PMID- 12206688
TI  - New oxorhenium(V) complexes from the widely used diaminedithiol (DADT) ligand
      system.
AB  - Synthesis of the 2,9-dimethyl-4,7-diaza-4-alkyl-2,9-decanedithiol (1, alkyl =
      morpholinylethyl in a, and alkyl = pyrrolidinylethyl in b), following a widely
      used synthetic scheme for diaminedithiol (DADT) ligands, led to the isolation of
      1-alkyl-2-(1'-methyl-1'-sulfanylethyl)-3-(2' '-methyl-2' '
      sulfanylpropyl)diazolidine (3) as the major product. Both ligands 1 and 2 gave
      complexes with the oxorhenium ReO(V) core. Ligand 1 gave the expected ReO[SNNS]
      complex (2) with the side chain on nitrogen in the syn configuration. Ligand 3
      gave, in the presence of a monodentate aromatic thiol, complexes of the
      ReO[SNN][S][S] (4) and ReO[SNN][S] type (5), respectively, in which the
      diazolidine ring has rearranged to a thiazolidine ring. Crystallographic analysis
      showed that in 4 the coordination geometry about the metal is distorted
      octahedral where the equatorial plane is defined by the sulfur and one of the
      nitrogen atoms of the ligand and the two sulfurs of the aromatic thiols, while
      the axial positions are occupied by the oxygen of the ReO core and the second
      nitrogen of the ligand. Specifically, complex 4a crystallizes in space group
      P2(1)/c, a = 15.63(1) A, b = 15.28(2) A, c = 16.07(1) A, beta = 113.78(2)
      degrees, V = 3512(5) A(3), Z = 4. Complex 4b crystallizes in space group P2(1)/n,
      a = 14.560(9) A, b = 14.804(9) A, c = 19.85(1) A, beta = 90.94(2) degrees, V =
      4278(1) A(3), Z = 4. In 5b, the coordination geometry is distorted square
      pyramidal with the SNN donor atom of the ligand and the aromatic thiol defining
      the equatorial plane and the doubly bonded oxygen occupying the apex of the
      pyramid. Complex 5b crystallizes in space group P(-)1, a = 9.387(5) A, b =
      11.306(5) A, c = 14.040(6) A, alpha = 84.51(1) degrees, beta = 84.45(2) degrees,
      gamma = 87.17(1) degrees, V = 1475(1) A(3), Z = 2. All isolated complexes are
      neutral and lipophilic. Complete assignments of (1)H and (13)C NMR resonances are
      reported.

PMID- 12206689
TI  - Flux growth of vanadyl pyrophosphate, (VO)(2)P(2)O(7), and spin dimer analysis of
      the spin exchange interactions of (VO)(2)P(2)O(7) and vanadyl hydrogen phosphate,
      VO(HPO(4)).0.5H(2)O.
AB  - Large transparent blue crystals of vanadyl pyrophosphate, (VO)(2)P(2)O(7), were
      grown from a phosphorus pentoxide flux, and the single-crystal X-ray structure of
      (VO)(2)P(2)O(7) was determined with high precision. On the basis of spin dimer
      analysis, we examined the spin exchange interactions of (VO)(2)P(2)O(7) and its
      precursor VO(HPO(4)).0.5H(2)O. Our analysis of (VO)(2)P(2)O(7) using two high
      precision crystal structures shows unambiguously that the V3-V4 chain has a
      larger spin gap than does the V1-V2 chain and that the super-superexchange (V
      O...O-V) interaction is stronger than the superexchange (V-O-V) interaction in
      the V3-V4 chain while the opposite is true in the V1-V2 chain. Our analysis of
      VO(HPO(4)).0.5H(2)O reveals that the superexchange interaction must dominate over
      the super-superexchange interaction, in disagreement with the conclusion from a
      powder neutron scattering study of VO(DPO(4)).0.5D(2)O.

PMID- 12206690
TI  - New synthetic routes to cationic rhenium tricarbonyl bipyridine complexes with
      labile ligands.
AB  - Triflate abstraction from the complex [Re(OTf)(CO)(3)(bipy)] (1) using the salt
      NaBAr'(4) (Ar' = 3,5-bis(trifluoromethyl)phenyl) in dichloromethane solution in
      the presence of L = PPh(3), NCMe, NCPh, imines, ketones, Et(2)O, THF, MeOH, and
      MeI affords cationic complexes [Re(L)(CO)(3)(bipy)](+) as their BAr'(4)(-) salts.
      The new complexes have been characterized spectroscopically and, for [Re(eta(1)
      O=C(Me)R)(CO)(3)(bipy)]BAr'(4) (R = CH(3), 6a; R = Ph, 6b), and
      [Re(THF)(CO)(3)(bipy)]BAr'(4) (9), also by single-crystal X-ray diffraction.
      Compared with conventional methodologies, the route reported here allows the
      coordination of a broader range of weakly coordinating ligands and requires
      considerably milder conditions. On the other hand, the reactions of lithium
      acetylides with [Re(THF)(CO)(3)(bipy)]BAr'(4) (9) can be used for the high-yield
      syntheses of rhenium alkynyls [Re(Ctbd1;CR)(CO)(3)(bipy)] (R = Ph, 12; R =
      SiMe(3), 13). Complex 9 was found to catalyze the aziridination of
      benzylideneaniline with ethyl diazoacetate.

PMID- 12206691
TI  - Binding of the two-valence-electron metal ions Sc(+), Ti(2+), and V(3+) to the
      second-row hydrides BeH(2), BH(3), NH(3), OH(2), and FH: a computational study.
AB  - We report results from a computational study of the binding in complexes formed
      from one of the transition-metal ions Sc(+), Ti(2+), or V(3+), each of which has
      two valence electrons outside an argon core, and one of the second-row hydrides
      FH, OH(2), NH(3), BH(3), or BeH(2). The complexes that involve the electron-rich
      ligands FH, OH(2), and NH(3) have strong ion-dipole components to their binding.
      There are large stabilization energies for sigma-interactions that transfer
      charge from occupied lone-pair natural bond orbitals on the F, O, or N atom of
      the (idealized) Lewis structure into empty non-Lewis orbitals on the metal ions;
      these interactions effectively increase electron density in the bonding region
      between the metal ion and liganded atom, and the metal ions in these complexes
      act in the capacity of Lewis acids. The complexes formed from the electron-poor
      hydrides BH(3) and BeH(2) consistently incorporate bridging hydrogen atoms to
      support binding, and there are large stabilization energies for interactions that
      transfer charge from the Be-H or B-H bonds into the region between the metal ion
      and liganded atom. The metal ions in Sc(+)-BeH(2), Ti(2+)-BeH(2), Ti(2+)-BH(3),
      and V(3+)-BH(3) act in the capacity of Lewis acids, whereas the scandium ion in
      Sc(+)-BH(3) acts as a Lewis base.

PMID- 12206692
TI  - Electronic structure, electrical and magnetic properties of RMo(8)O(14) compounds
      (R = La, Ce, Pr, Nd, Sm) containing bicapped Mo(8) clusters.
AB  - Magnetic and electrical resistivity properties of RMo(8)O(14) (R = La, Ce, Pr,
      Nd, Sm) compounds containing different bicapped-octahedral Mo(8) clusters are
      discussed. Extended Huckel (EH) molecular calculations were carried out in order
      to study the influence of the position of metal capping atoms on the electronic
      structure of different Mo(8) isomers. Different optimal metal electron counts are
      possible for these clusters. Periodic density functional calculations confirm the
      molecular character of these compounds and allow the understanding of their
      semiconducting and magnetic properties.

PMID- 12206693
TI  - Gallium and gallium dichloride, new solid-state reductants in preparative
      transition metal chemistry. New, lower temperature syntheses and convenient
      isolation of hexatantalum tetradecachloride octahydrate, Ta(6)(mu
      Cl)(12)Cl(2)(OH(2))(4).4H(2)O, and synthesis and solid-state structure of a
      tetraalkylammonium derivative, [N(CH(2)Ph)Bu(3)](4)[Ta(6)(mu-Cl)(12)Cl(6)], of
      the reduced [Ta(6)(mu-Cl)(12)](2+) cluster core(1).
AB  - Reduction of TaCl(5) with either Ga or Ga(2)Cl(4), in the presence of NaCl, in a
      sealed borosilicate glass ampule at 500 degrees C, followed by aqueous Soxhlet
      extraction and treatment with SnCl(2) and hydrochloric acid, yielded Ta(6)(mu
      Cl)(12)Cl(2)(OH(2))(4).4H(2)O in 92% (Ga) or 96% (Ga(2)Cl(4)) yield. Ga(2)Cl(4),
      a probable intermediate in the Ga-based reduction, is a more convenient reductant
      than Ga because it is readily dispersed in the reaction mixture, and these
      mixtures do not require homogenizations in order to afford high yields. Ta(6)(mu
      Cl)(12)Cl(2)(OH(2))(4).4H(2)O was converted by ligand exchange to the first
      tetraalkylammonium derivative, [N(CH(2)Ph)Bu(3)](4)[Ta(6)(mu-Cl)(12)Cl(6)], of
      the reduced cluster core Ta(6)(mu-Cl)(12)(2+), in 88% yield.
      [N(CH(2)Ph)Bu(3)](4)[Ta(6)(mu-Cl)(12)Cl(6)] crystallizes from 1,2
      dichloroethane/toluene mixtures in two crystalline morphologies, a nonsolvated
      cubic form and a solvated needle form. The solid-state molecular structures of
      both crystalline morphologies of [N(CH(2)Ph)Bu(3)](4)[Ta(6)(mu-Cl)(12)Cl(6)]
      consist of octahedral, 16 VEC hexatantalum cluster anions with an average Ta-Ta
      distance of 2.900[2] A, a Ta-Cl(bridge) distance of 2.463[2] A, a Ta-Cl(terminal)
      distance of 2.567[5] A, and a Ta-Cl-Ta angle of 72.1[1] degrees for the cubic
      form, and for the solvated needle morphology, an average Ta-Ta distance of
      2.900[1] A, a Ta-Cl(bridge) distance of 2.461[1]A, a Ta-Cl(terminal) distance of
      2.567[3] A, and a Ta-Cl-Ta angle of 72.19[7] degrees.

PMID- 12206694
TI  - The effect of ligand charge on the coordination geometry of an Fe(III)ion: five-
      and six-coordinate Fe(III) complexes of tris(2-benzimidazolylmethyl)amine.
AB  - By using the tripodal tetradentate ligand tris(2-benzimidazolylmethyl)amine
      (H(3)ntb), which can have several charge states depending on the number of
      secondary amine protons, mononuclear octahedral and dinuclear trigonal
      bipyramidal Fe(III) complexes were prepared. The reaction of mononuclear
      octahedral [Fe(III)(H(3)ntb)Cl(2)]ClO(4), 1, with 3 equiv of sec-butylamine in
      methanol led to the formation of mononuclear cis-dimethoxo octahedral
      Fe(III)(H(2)ntb)(OMe)(2), 2. One equivalent of the sec-butylamine was used to
      generate the monoanionic H(2)ntb(-) ligand where one of the three amines in the
      benzimidazolyl groups was deprotonated. The remaining 2 equiv were used to
      generate two methoxides that were coordinated to the octahedral Fe(III) ion in a
      cis fashion as demonstrated by the chlorides in 1. Reaction of 1 with excess (7
      equiv) sec-butylamine generated the doubly deprotonated dianionic Hntb(2-) that
      stabilized the dinuclear mu-oxo Fe(III)(2)O(Hntb)(2), 3, adopting a five
      coordinate trigonal bipyramidal geometry. The magnetic data for 3 are consistent
      with the antiferromagnetically coupled Fe(III) (S = 5/2) sites with the coupling
      constant J = -127 cm(-1).

PMID- 12206695
TI  - Tris(dimethylamino)oxosulfonium difluorotrimethylsilicate,
      (Me(2)N)(3)SO(+)Me(3)SiF(2)(-) (TAOS Fluoride).
AB  - In the OSF(4)/Me(2)NSiMe(3) system besides the long known Me(2)NS(O)F(3) only the
      trisubstituted derivative is isolated as (Me(2)N)(3)SO(+)Me(3)SiF(2)(-) (3).
      Similar to (Me(2)N)(3)S(+)Me(3)SiF(2)(-) compound 3 is an excellent fluoride ion
      donor. With AsF(5) and HF the corresponding hexafluoroarsenate
      (Me(2)N)(3)SO(+)AsF(6)(-) (4) and the hydrogen bifluoride (Me(2)N)(3)SO(+)HF(2)(
      ) (5) are formed in almost quantitative yield. X-ray structure determinations of
      3-5 surprisingly showed two different types of structures for the cation. In 3
      and 5 this cation has C(3) symmetry, while in the hexafluoroarsenate 4 a
      (Me(2)N)(3)S(+)-like structure with C(s)() symmetry is determined. The
      experimental results for (Me(2)N)(3)SO(+) and (Me(2)N)(3)S(+) are compared with
      theoretical calculations for these cations and their isoelectronic neutral
      counterparts, the phosphorus amides (Me(2)N)(3)PO and (Me(2)N)(3)P, respectively.

PMID- 12206696
TI  - Flattening of rhodium vertices in mixed rhodium-nickel carbonyl clusters:
      relationships to borane and zintl ion structures.
AB  - The flattened deltahedra and related polyhedra found in hypoelectronic bare group
      13 metal cluster anions are also found in some anionic mixed rhodium-nickel
      carbonyl clusters. In all cases the rhodium vertices rather than the nickel
      vertices are involved in the flattening process so that the rhodium vertices
      contribute four internal orbitals and the nickel vertices three internal orbitals
      to the skeletal bonding of the cluster. Thus, the 11-vertex cluster
      Rh(5)Ni(6)(CO)(21)(3-) has a D(3h) triflattened pentacapped trigonal prismatic
      structure similar to that found in the In(11)(7-) anion of the intermetallic
      K(8)In(11). Similarly the polyhedra in the 11-vertex cluster RhNi(10)(CO)(19)(3-)
      and the 9-vertex cluster Rh(3)Ni(6)(CO)(17)(3-) are both derived from a 10-vertex
      isocloso polyhedron by capping (for RhNi(10)(CO)(19)(3-)) or vertex removal (for
      Rh(3)Ni(6)(CO)(17)(3-)) followed by flattening all of the rhodium vertices. A
      D(3h) icosahedron with flattened rhodium vertices is found in the 12-vertex
      cluster Rh(3)Ni(9)(CO)(22)(3-).

PMID- 12206697
TI  - Kinetics and mechanism of oxygen atom abstraction from a dioxo-rhenium(VII)
      complex.
AB  - The kinetics of reaction between triarylphosphanes and two newly prepared
      dioxorhenium(VII) compounds has been evaluated. The compounds are
      MeRe(VII)(O)(2)("O,S") in which "O,S" represents an alkoxo, thiolato chelating
      ligand. With MeReO(3), ligands derived from 1-mercaptoethanol and 1-mercapto-2
      propanol form MeRe(O)(2)(met), 2, and MeRe(O)(2)(m2p), 3. These compounds persist
      in chloroform solution for several hours at room temperature and for 2-3 weeks at
      -22 degrees C, particularly when water is carefully excluded. They were obtained
      as red oils with clean (1)H NMR spectra, but attempts to obtain pure, crystalline
      products were not successful because one decomposition pathway shows a kinetic
      order >1. The fastest reaction occurs between P(p-MeOC(6)H(4))(3) and 2; k(298) =
      215(7) L mol(-1) s(-1) in chloroform at 25(1) degrees C. The other rate constants
      follow a Hammett correlation against 3sigma, with rho = -0.69(7). This study
      relates to oxygen atom transfer reactions catalyzed by MeReO(mtp)PPh(3), 1, in
      which MeRe(O)(2)(mtp), 4, is a postulated intermediate that does not build up to
      a measurable concentration during the catalytic cycle. Compound 2 does not react
      with MeSTol, but MeS(O)Tol was formed when tert-butyl hydroperoxide was added.
      This suggests that equilibrium lies to the left in this reaction, 2 + MeSTol + L
      = MeReO(met)L + MeS(O)Tol, and is drawn to the right by a reaction between
      MeReO(met)L and the hydroperoxide. Triphenyl arsane does not react with 2, but
      thermodynamic versus kinetic barriers were not resolved.

PMID- 12206698
TI  - From monomer zinc-oxamato complexes to tetranuclear inverse 12-membered and
      octanuclear 12-membered metallacrowns.
AB  - Interaction of ZnCl(2) with Hpko (Hpko, di-2-pyridyl-ketonoxime) results in the
      formation of a uninuclear Zn(Hpko)Cl(2) (1) compound or in a 12-membered
      tetranuclear metallacrown (OH)(2)[inv12-MC(Zn(II)N(pko))-4]Cl(2) (2) depending on
      the pH of the mother solution. The addition of H(3)shi (H(3)shi,
      salicylhydroxamic acid) leads to the formation of the octanuclear 12-membered
      tetranuclear metallacrown [Zn(2)]([Zn(2)(pko)(4)][12-MC(Zn(II)N(shi))
      4](CH(3)OH)(2)) (3). The metallacrown core of 2 is characterized as "inverse"
      because the zinc atoms, rather than oxygen atoms, are oriented toward the central
      cavity. Two triply bridging hydroxides are accommodated in the center of the
      metallacrown ring. The pko(-) ligands form a propeller configuration that imposes
      absolute stereoisomerism with Lambda and Delta chirality. Each hydroxo oxygen
      bridges two octahedral zinc atoms and a tetrahedral one. The octanuclear cluster
      Zn(8)(shi)(4)(pko)(4)(CH(3)OH)(2) contains a 12-membered tetranuclear
      metallacrown core constructed by four Zn metal atoms and four shi(3-) ligands.
      So, a part of the cluster can be described as having the formally anionic [12
      MC(Zn(II)N(shi))-4](4-) core. Two of the zinc atoms are in octahedral
      coordination environment while for the other two the geometry is best described
      as distorted trigonal bipyramidal. The metallacrown core accommodates a binuclear
      compound with the formula [Zn(2)(pko)(4)]. Two of the ring metal ions create
      binuclear units with two zinc ions, respectively, with two oxamato oxygens, and
      two phenolato oxygens, of the four interlinked shi(3-) ligands acting as bridging
      atoms.

PMID- 12206699
TI  - Conformation versus coordination: synthesis and structural investigations of
      tellurium(II) dithiolates derived from beta-donor-substituted thiols.
AB  - New methods of preparing tellurium(II) dithiolates, Te(SR)(2), are presented.
      Te(SCH(2)CH(2)OAc)(2), 1, was made from Te(SCH(2)CH(2)OH)(2) by acetylation of
      the hydroxyl groups. Te(SCH(2)CH(2)SAc)(2), 2, [Te(SCH(2)CH(2)NH(3))(2)]Cl(2), 3,
      and Te(SC(6)H(4)(o-NH(2)))(2), 4, were synthesized by ligand exchange reactions
      of Te(S(t)Bu)(2) with 2 equiv of HSCH(2)CH(2)SAc, [HSCH(2)CH(2)NH(3)]Cl, and
      HSC(6)H(4)(o-NH(2)), respectively. Of all compounds, 4 exhibits the strongest
      thermal sensitivity toward decomposition and the largest low-field shift of the
      (125)Te NMR signal, two features that are attributed to weak Te.N interactions.
      The structural parameters of the CSTeSC unit exhibit very similar values for all
      four compounds, while the torsion angles of the side chains differ between the
      molecules, a feature rationalized by ab initio studies. In the solid state,
      different kinds of intermolecular aggregation and contacts to the Te atoms are
      present. 1 and 2 crystallize in the same space group (orthorhombic, Pbcn) and
      exhibit C(2) symmetric molecules, with two intermolecular Te.S contacts, leading
      to a trapezoidal coordination mode of the Te atoms. SCCE and C(S)CEC (with E = O,
      S) torsion angles represent the major differences between 1 and 2, which are
      attributed to their unlike intermolecular hydrogen bridges. In the solid state
      structure of 3, [Te(SCH(2)CH(2)NH(3))(2)](2+) cations and Cl(-) anions form a
      three-dimensional network via N-H...Cl and C-H...Cl hydrogen bonds (triclinic, P(
      )1). Two neighboring [Te(SCH(2)CH(2)NH(3))(2)](2+) cations are linked via two
      Te...S contacts, and each Te atom forms one additional Te...Cl contact, resulting
      in a slightly distorted trapezoidal coordination mode. In the solid state
      structure of 4, adjacent molecules form Te...Te and Te...N contacts as well as
      hydrogen bridges. Two chemically different Te atoms are present, both of which
      are tetracoordinate with distorted sawhorse configurations. The absence of
      intramolecular Te...O, Te...S, or Te...N contacts in 1, 2, and 4, respectively,
      is attributed to the conformational rigidity of the CSTeS unit, where
      conformation ruling coordination is the case.

PMID- 12206700
TI  - Spectroscopic and structural assignment of the absolute stereochemistry in a
      series of 1,2-difluorovinyl organometalloids. The first crystallographic
      characterization and structural series of group 14 fluorovinyl compounds.
AB  - The group 14 trifluorovinyl compounds Ph(3)ECF=CF(2) (E = Ge, Sn, Pb) have been
      prepared in high yield by the low-temperature reaction of the triphenylelement
      halide with trifluorovinyllithium, generated from tetrafluoroethane (CF(3)CH(2)F,
      HFC-134a) and 2 equiv of n-butyllithium. The X-ray crystal structures of these
      materials have been obtained, so affording the first structural series for such
      species. Subsequent reaction of Ph(3)GeCF=CF(2) with LiAlH(4) and a range of
      organolithium reagents has led to preparation of the 1,2-difluorovinylgermanes
      Ph(3)GeCF=CFR (R = H, Me, n-Bu, t-Bu, Ph). Multinuclear NMR spectroscopic and X
      ray crystallographic studies of these compounds have been undertaken and have
      shown unequivocally the exclusive trans-geometry of the 1,2-difluorovinyl moiety.

PMID- 12206701
TI  - Characterization of a soluble molecular magnet: unusual magnetic behavior of
      cyano-bridged Gd(III)-Cr(III) complexes with one-dimensional and nanoscaled
      square structures.
AB  - Two cyano-bridged Gd(III)-Cr(III) complexes
      [Gd(urea)(4)(H(2)O)(2)](2)[Cr(CN)(6)](2) (1) and
      ([Gd(capro)(2)(H(2)O)(4)Cr(CN)(6)].H(2)O)(n)(2) (capro represents caprolactam)
      have been synthesized and characterized structurally and magnetically. Complex 1
      has a tetranuclear Gd(2)Cr(2) square structure, in which two cis-CN(-) ligands of
      each [Cr(CN)(6)] link two [Gd(urea)(4)(H(2)O)(2)] groups and in turn, two
      [Gd(urea)(4)(H(2)O)(2)] link two [Cr(CN)(6)] in a cis fashion. Complex 2 is
      composed of 1D chains with alternating [Gd(capro)(2)(H(2)O)(4)] and [Cr(CN)(6)]
      moieties connected by the trans-CN(-) ligands of [Cr(CN)(6)]. The dehydration of
      2 at 120 degrees C generates a new complex, [Gd(capro)(2)(H(2)O)(2)Cr(CN)(6)]
      (2'). Magnetic studies show the existence of antiferromagnetic Gd(III)-Cr(III)
      interaction in these complexes. On the basis of the tetranuclear model, the
      magnetic susceptibilities of 1 have been analyzed giving the intermetallic
      magnetic coupling constant of -0.36 cm(-1). Complex 2' exhibits a ferrimagnetic
      order below 2.1 K. Interestingly, 2' is quite soluble in water, and slow
      evaporation of the solution gives the hydrated complex 2. Therefore, 2' is a
      soluble molecular magnet, and this significant behavior implies potential
      applications. Isothermal magnetization measurements of 2' and other cyano-bridged
      Gd(III)-Cr(III) molecular magnets show unusual field-induced metamagnetic
      behavior from the ferrimagnetic ground state to the ferromagnetic state. Field
      dependence of magnetization of the cyano-bridged Gd(III)-Cr(III) complexes shows
      unusual field-induced metamagnetic behavior from the ferrimagnetic ground state
      to the ferromagnetic state.

PMID- 12206702
TI  - Metallic conductivity and ferromagnetic interaction of iron(III) d spins in the
      needle crystals of (ethylenedithiotetrathiafulvalenoquinone-1,3
      dithiolemethide)(2).FeBr(4) salt.
AB  - The 2:1 charge-transfer (CT) salts (1(2).FeBr(4) and 1(2).GaBr(4)) of
      ethylenedithiotetrathiafulvalenoquinone-1,3-dithiolemethide (1) with FeBr(4)(-)
      and GaBr(4)(-) counteranions were obtained as needle crystals, whose structures
      are almost the same as each other. The 1 molecules form a one dimensionally
      stacked column with alternation of their molecular axis direction, while the
      counteranions are aligned in parallel with the 1-stacked columns with the
      direction of their distorted-tetrahedral geometry maintained. The room
      temperature electrical conductivities measured on the single crystals of
      1(2).FeBr(4) and 1(2).GaBr(4) were 4.6 and 2.1 S cm(-1), respectively. From the
      temperature dependences of their electrical conductivities in both cases the
      electrical conducting properties were metallic between ca. 170 and 300 K, but
      below ca. 170 K converted to be semiconducting and continued till 5 K, although
      the activation energies are very small (4-10 meV). For 1(2).FeBr(4) very weak and
      antiferromagnetic interaction occurred between the d spins of FeBr(4)(-) ions in
      the temperature range of ca. 1-300 K. However, below ca. 15 K the ferromagnetic
      interaction was reversely preferential possibly by participation of the pi spin
      of 1.

PMID- 12206703
TI  - Dichlorogallane (HGaCl(2))(2): its molecular structure and synthetic potential.
AB  - Dichlorogallane (HGaCl(2))(2) is readily prepared from gallium trichloride and
      triethylsilane in quantitative yield. Its crystal structure has been determined
      by single crystal X-ray diffraction. In the chlorine-bridged dimers of
      crystallographically imposed C(2h) symmetry, the terminal hydrogen atoms are in
      trans positions. In the reaction with 2 equiv of triethylphosphine, the
      mononuclear complex (Et(3)P)GaHCl(2) is formed. Thermal decomposition of
      (HGaCl(2))(2) affords hydrogen gas and quantitative yields of "GaCl(2)" as mixed
      valent Ga[GaCl(4)]. Treatment of this product with triethylphosphine gives the
      symmetrical, Ga-Ga-bonded gallium(II) complex [GaCl(2)(PEt(3))](2) with an ethane
      type structure and with the phosphine ligands in a single-trans conformation. The
      corresponding [GaBr(2)(PEt(3))](2) complex is prepared from Ga[GaBr(4)] and has
      an analogous structure. (Et(3)P)GaCl(3) has been synthesized and structurally
      characterized as a reference compound.

PMID- 12206704
TI  - Reactions of N-silylphosphoranimines with alcohols: synthesis and structure of
      cyclotriphosphazenes with nongeminal methyl and phenyl substituents.
AB  - The reactions of Me(3)SiN=P(OR")RR'(R" = Ph, CH(2)CF(3); R, R' = Me, Ph) with
      alcohols were investigated. With nonequivalent amounts of CF(3)CH(2)OH, the
      reactions produced high yields of the cyclic phosphazene (Me(2)PN)(3) and both
      the cis and trans isomers of nongeminally substituted [(Ph)(Me)PN](3). The
      isomers of this new cyclic phosphazene were separated by column chromatography
      and characterized by NMR and IR spectroscopy, elemental analysis, and X-ray
      crystallography. Crystals of the cis isomer 6a have a monoclinic crystal system,
      while the trans isomer 6b has a triclinic crystal system with two different
      molecules in an asymmetric unit. The bond lengths and bond angles are very
      similar to those of the simpler cyclic trimers (Me(2)PN)(3) and (Ph(2)PN)(3.) A
      likely pathway for the formation of these compounds is discussed.

PMID- 12206705
TI  - Kinetic and mechanistic studies of sulfur transfer from imidomethylrhenium
      sulfides.
AB  - The bis(2,6-diisopropylphenylimido)methylrhenium(VII) sulfide dimer,
      [CH(3)Re(NAr)(2)](2)(mu-S)(2) (1), reacts with a 1:1 amount of a phosphine or an
      alkyl isocyanide to yield a dimeric rhenium(VI) species, [CH(3)Re(NAr)(2)](2)(mu
      S) (2), which has been structurally characterized. The two rhenium atoms in 2 are
      within bonding distance, 280 pm, more than 90 pm shorter than in 1. With excess
      L, 1 reacts to give a monomeric rhenium(V) complex, CH(3)Re(NAr)(2)L(2) (3A, L =
      PZ(3), Z = alkyl, aryl; 3B, L = isocyanide). The rate of formation of 3A is first
      order with respect to [1] and second-order with respect to monodentate phosphine
      concentrations. With bidentate phosphines, however, the order with respect to the
      phosphine drops to unity. The addition of another (nonoxidizable) coordinating
      ligand, such as pyridine or one of its derivatives, accelerates the formation of
      3A. In the presence of a pyridine ligand the reaction is first-order with respect
      to phosphine concentration, both monodentate and bidentate. The reactions between
      phosphines and 2 are slower than those with 1, which excludes
      [CH(3)Re(NAr)(2)](2)(mu-S) from being the intermediate in the reactions of 1. To
      account for that, we have proposed an intervening species that partitions between
      transformation to 3 with excess L and to 2 otherwise.

PMID- 12206706
TI  - Peroxynitrite decomposition activity of iron porphyrin complexes.
AB  - Peroxynitrite (ONOO(-)/ONOOH), a putative cytotoxin formed by combination of
      nitric oxide (NO.) and superoxide (HO(2)(.)) radicals, is decomposed
      catalytically by micromolar concentrations of water-soluble Fe(III) porphyrin
      complexes, including 5,10,15,20-tetrakis(2',4',6'-trimethyl-3,5
      disulfonatophenyl)porphyrinatoferrate(7-), Fe(TMPS); 5,10,15,20-tetrakis(4'
      sulfonatophenyl)porphyrinatoiron(3-), Fe(TPPS); and 5,10,15,20-tetrakis(N-methyl
      4'-pyridyl) porphyrinatoiron(5+), Fe(TMPyP). Spectroscopic (UV-visible), kinetic
      (stopped-flow), and product (ion chromatography) studies reveal that the
      catalyzed reaction is a net isomerization of peroxynitrite to nitrate (NO(3)(-)).
      One-electron catalyst oxidation forms an oxoFe(IV) intermediate and nitrogen
      dioxide, and recombination of these species is proposed to regenerate
      peroxynitrite or to yield nitrate. Michaelis-Menten kinetics are maintained
      accordingly over an initial peroxynitrite concentration range of 40-610 microM at
      5.0 microM catalyst concentrations, with K(m) in the range 370-620 microM and
      limiting turnover rates in the range of 200-600 s(-1). Control experiments
      indicate that nitrite is not a kinetically competent reductant toward the
      oxidized intermediates, thus ruling out a significant role for NO(2)(.)
      hydrolysis in catalyst turnover. However, ascorbic acid can intercept the
      catalytic intermediates, thus directing product distributions toward nitrite and
      accelerating catalysis to the oxidation limit. Additional mechanistic details are
      proposed on the basis of these and various other kinetic observations,
      specifically including rate effects of catalyst and peroxynitrite concentrations,
      solution pH, and isotopic composition.

PMID- 12206707
TI  - Zinc(II)/ketoxime system as a simple and efficient catalyst for hydrolysis of
      organonitriles.
AB  - The hydrolysis of sterically hindered and unhindered alkyl nitriles, and also of
      benzyl and phenyl nitriles RCN (R = Me, CH(2)Cl, Et, n-Pr, i-Pr, n-Bu, t-Bu, p
      MeOC(6)H(4)CH(2), Ph), to carboxamides is catalyzed by a novel system of superior
      simplicity consisting of cheap, widely commercially available, and rather
      environmentally friendly compounds, that is, a ZnX(2)/ketoxime combination, but
      it does not proceed at all with either the zinc salt or the ketoxime taken alone.
      The nature of the anion X(-) in the zinc salt (X = NO(3), Cl, CF(3)SO(3)) or of
      the ketoxime (Me(2)C=NOH, C(4)H(8)C=NOH, C(5)H(10)C=NOH) does not affect strongly
      the catalytic properties of the system, but the best results were obtained so far
      with a Zn(NO(3))(2).6H(2)O/2-propanone oxime molar ratio of 1:4; turnover numbers
      are typically above ca. 100 but reach as high as 1000 for p
      MeOC(6)H(4)CH(2)C(=O)NH(2). The previously unknown structures of the two
      carboxamide products n-BuC(=O)NH(2) and p-MeOC(6)H(4)CH(2)C(=O)NH(2) were
      determined by X-ray diffraction studies. The complexes [ZnX(2)(R(2)C=NOH)(2)] (X
      = Cl, R(2) = 2Me, C(4)H(8), C(5)H(10); X = NO(3), R = C(4)H(8)), prepared by
      heating the appropriate zinc salts with 2 equiv of the ketoxime in acetone and
      characterized by C, H, N analyses, FAB-MS, (1)H and (13)C[(1)H] NMR
      spectroscopies, and also X-ray crystallography (for X = Cl, R(2) = 2Me; X =
      NO(3), R = C(4)H(8)), proved to be catalyst precursors in the conversions because
      the activity of these species is high only in the presence of 2 equiv of the
      ketoxime.

PMID- 12206708
TI  - Inter- and intramolecular pi-stacking interactions in cis-bis[1-(9
      anthracene)]phosphirane complexes of platinum(II).
AB  - The bis[1-(9-anthracene)phosphirane]dithiolatoplatinum(II) complexes, Pt[1-(9
      anthracene)phosphirane](2)(dithiolate), where dithiolate = 1,1-dimethoxycarbonyl
      ethylene-2,2-dithiolate (dmdt) (2), 1,1-diethoxycarbonyl-ethylene-2,2-dithiolate
      (dedt) (3), 1-ethoxycarbonyl-1-cyano-ethylene-2, 2-dithiolate (ecdt) (4), and 1,1
      dicyano-ethylene-2,2-dithiolate (dcdt) (5), were prepared from cis-dichlorobis[1
      (9-anthracene)phosphirane]platinum(II) (1). Complexes 3 and 5 were characterized
      by X-ray crystallography and were found to have vastly different crystal and
      molecular structures. The crystal and molecular structure of 3 is dominated by
      intramolecular pi-stacking between the anthracene rings of the cis
      bis(anthracene)phosphiranes with a ring...ring separation of 3.48(6) A. The
      molecular structure of 5 does not exhibit an intramolecular interaction between
      the anthracene rings. Instead, the crystal structure of 5shows significant
      intermolecular pi-stacking between the anthracene rings of the phosphirane
      ligands of adjacent molecules packed in the crystal lattice. The intermolecular
      stacking interaction results in a ring...ring separation of 3.33(4) A. Complexes
      2-5 were found to emit at 530 nm at low temperatures in the solid state. Complex
      5 emits strongly in fluid THF or benzene solution at 430 nm.

PMID- 12206709
TI  - Protonation state of the equatorial ligands and dynamics of the OH...O units in a
      cobaloxime biomimetic.
AB  - The protonation state of the dimethylglyoxime ligands in the B(12) coenzyme
      biomimetic [Co(CCl=CHCl)(dmgH)(2)(py)].CHCl(3) was investigated by using first
      principles molecular dynamics. Our simulations at 173 and 300 K reveal that one
      of the oxime protons remains bonded to a nitroxyl group, while the proton of the
      second NO...H-ON unit is essentially shared with similar probability between the
      two oxygen atoms. This reconciles the results of the experimental determination
      (Jones, P. G.; Yang, L.; Steinborn, D. Acta Cryst. 1996, C52, 2399), showing all
      N-O distances as equivalent, with the commonly accepted rule that the protonation
      state of the dimethylglyoxime ligands can be identified by the different N-O
      distances. Further aspects of the dynamics of the OH...O units, in relation to
      the occurrence of weak CH...O intermolecular interactions, are analyzed.

PMID- 12206710
TI  - Stoichiometric and catalytic oxygen activation by trimesityliridium(III).
AB  - Trimesityliridium(III) (mesityl = 2,4,6-trimethylphenyl) reacts with O(2) to form
      oxotrimesityliridium(V), (mes)(3)Ir=O, in a reaction that is cleanly second order
      in iridium. In contrast to initial reports by Wilkinson, there is no evidence for
      substantial accumulation of an intermediate in this reaction. The oxo complex
      (mes)(3)Ir=O oxidizes triphenylphosphine to triphenylphosphine oxide in a second
      order reaction with DeltaH++ = 10.04 +/- 0.16 kcal/mol and DeltaS++ = -21.6 +/-
      0.5 cal/(mol.K) in 1,2-dichloroethane. Triphenylarsine is also oxidized, though
      over an order of magnitude more slowly. Ir(mes)(3) binds PPh(3) reversibly
      (K(assoc) = 84 +/- 3 M(-1) in toluene at 20 degrees C) to form an unsymmetrical,
      sawhorse-shaped four-coordinate complex, whose temperature-dependent NMR spectra
      reveal a variety of dynamic processes. Oxygen atom transfer from (mes)(3)Ir=O and
      dioxygen activation by (mes)(3)Ir can be combined to allow catalytic aerobic
      oxidations of triphenylphosphine at room temperature and atmospheric pressure
      with overall activity (approximately 60 turnovers/h) comparable to the fastest
      reported catalysts. A kinetic model that uses the rates measured for dioxygen
      activation, atom transfer, and phosphine binding describes the observed catalytic
      behavior well. Oxotrimesityliridium does not react with sulfides, sulfoxides,
      alcohols, or alkenes, apparently for kinetic reasons.

PMID- 12206711
TI  - Synthesis and reactions of group 6 metal half-sandwich complexes of 2,2
      dicyanoethylene-1,1-dichalcogenolates [(Cp*)M[E(2)C=C(CN)(2)](2)]-(M = Mo, W; E =
      S, Se).
AB  - A series of group 6 transition metal half-sandwich complexes with 1,1
      dichalcogenide ligands have been prepared by the reactions of Cp*MCl(4)(Cp* =
      eta(5)-C(5)Me(5); M = Mo, W) with the potassium salt of 2,2-dicyanoethylene-1,1
      dithiolate, (KS)(2)C=C(CN)(2) (K(2)-i-mnt), or the analogous seleno compound,
      (KSe)(2)C=C(CN)(2) (K(2)-i-mns). The reaction of Cp*MCl(4) with (KS)(2)C=C(CN)(2)
      in a 1:3 molar ratio in CH(3)CN gave rise to K[Cp*M(S(2)C=C(CN)(2))(2)] (M = Mo,
      1a, 74%; M = W, 2a, 46%). Under the same conditions, the reaction of Cp*MoCl(4)
      with 3 equiv of (KSe)(2)C=C(CN)(2) afforded K[Cp*Mo(Se(2)C=C(CN)(2))(2)] (3a) and
      K[Cp*Mo(Se(2)C=C(CN)(2))(Se(Se(2))C=C(CN)(2))] (4) in respective yields of 45%
      and 25%. Cation exchange reactions of 1a, 2a, and 3a with Et(4)NBr resulted in
      isolation of (Et(4)N)[Cp*Mo(S(2)C=C(CN)(2))(2)] (1b),
      (Et(4)N)[Cp*W(S(2)C=C(CN)(2))(2)] (2b), and (Et(4)N)[Cp*Mo(Se(2)C=C(CN)(2))(2)]
      (3b), respectively. Complex 4 crystallized with one THF and one CH(3)CN molecule
      as a three-dimensional network structure. Inspection of the reaction of Cp*WCl(4)
      with (KSe)(2)C=C(CN)(2) by ESI-MS revealed the existence of three species in
      CH(3)CN, [Cp*W(Se(2)C=C(CN)(2))(2)]-,
      [Cp*W(Se(2)C=C(CN)(2))(Se(Se(2))C=C(CN)(2))]-, and [Cp*W(Se(Se(2))C=C(CN)(2))(2)]
      , of which [Cp*W(Se(2)C=C(CN)(2))(Se(Se(2))C=C(CN)(2))]-(5) was isolated as the
      main product. Treatment of 2a with 1/4 equiv of S(8) in refluxing THF resulted in
      sulfur insertion and gave rise to K[Cp*W(S(2)C=C(CN)(2))(S(S(2))C=C(CN)(2))](6),
      which crystallized with two THF molecules forming a three-dimensional network
      structure. 6 can also be prepared by refluxing 2a with 1/4 equiv of S(8) in THF.
      3a readily added one Se atom upon treatment with 1 mol of Se powder in THF to
      give 4 in high yield, while the treatment of 3a or 4 with 2 equiv of Na(2)Se in
      THF led to formation of a dinuclear complex [(Cp*Mo)(2)(mu-Se)(mu
      Se(Se(3))C=C(CN)(2))] (7). The structure of 7 consists of two Cp*Mo units bridged
      by a Se(2-) and a [Se(Se(3))C=C(CN)(2)](2-) ligand in which the triselenido group
      is arranged in a nearly linear way (163 degrees). The reaction of 2a with 2 equiv
      of CuBr in CH(3)CN yielded a trinuclear complex [Cp*WCu(2)(mu-Br)(mu(3)
      S(2)C=C(CN)(2))(2)] (8), which crystallized with one CH(3)CN and generated a one
      dimensional chain polymer through bonding of Cu to the N of the cyano groups.

PMID- 12206712
TI  - (RO)(2)Ta[tris(2-oxy-3,5-dimethylbenzyl)amine]: structure and lactide
      polymerization activities.
AB  - The novel atrane-like six-coordinate (RO)(2)TaL complexes [where R = Me or Et and
      L = tris(2-oxy-3,5-dimethylbenzyl)amine] containing three six-membered rings have
      been synthesized and characterized. The R = Me complex is the first group 5
      representative of this class of compounds structurally characterized by X-ray
      means. Somewhat surprisingly, these compounds failed to function as single-site
      initiators for the polymerization of l-LA to isotactic PLA and rac-LA to atactic
      PLA, whereas Ta(OEt)(5) and two titanium analogues ROTiL (where R = 2,6-di-i
      PrC(6)H(3) and i-Pr) as well as Ti(O-i-Pr)(4) were effective catalysts for both
      polymerizations.

PMID- 12206713
TI  - Cell population modelling of yeast glycolytic oscillations.
AB  - We investigated a cell-population modelling technique in which the population is
      constructed from an ensemble of individual cell models. The average value or the
      number distribution of any intracellular property captured by the individual cell
      model can be calculated by simulation of a sufficient number of individual cells.
      The proposed method is applied to a simple model of yeast glycolytic oscillations
      where synchronization of the cell population is mediated by the action of an
      excreted metabolite. We show that smooth one-dimensional distributions can be
      obtained with ensembles comprising 1000 individual cells. Random variations in
      the state and/or structure of individual cells are shown to produce complex
      dynamic behaviours which cannot be adequately captured by small ensembles.

PMID- 12206714
TI  - A locus on human chromosome 20 contains several genes expressing protease
      inhibitor domains with homology to whey acidic protein.
AB  - A locus containing 14 genes, encoding protein domains that have homology with
      whey acidic protein (WAP), has been identified in a region of 678 kb on human
      chromosome 20q12-13.1. Among them are genes of the known or postulated protease
      inhibitors elafin, secretory leucocyte protease inhibitor, human epididymis gene
      product 4, eppin, and huWAP2. Nucleotide sequences of full-length transcripts
      were obtained from cDNA fragments generated by rapid amplification of cDNA ends.
      Characteristic features of the genes are that the upstream promoter regions are
      devoid of TATA-boxes and that the coding nucleotides are divided into distinct
      exons for the signal peptide and for each WAP domain. In most cases, there is
      also a separate exon encompassing a few terminal codons and the 3' untranslated
      nucleotides. There are also examples of mixed type inhibitors, that encode
      inhibitor domains of both WAP and Kunitz types. Several of the genes appear to be
      expressed ubiquitously, but, in most cases, the highest transcript levels are
      found in epididymis followed by testis and trachea. Some of the genes also
      display high transcript levels in neural tissues. Potential biological roles of
      protein products could be in host defence against invading micro-organisms or in
      the regulation of endogenous proteolytic enzymes, of which those originating from
      the kallikrein gene locus on chromosome 19 are of particular interest.

PMID- 12206719
TI  - Oz reprised: training and experience vs. greed.

PMID- 12206720
TI  - Interstitial laser hyperthermia for colorectal liver metastases: the effect of
      thermal sensitization and the use of a cylindrical diffuser tip on tumor
      necrosis.
AB  - OBJECTIVE: Our aim in this study was to investigate the characteristics of a
      diffuser-tipped optical fiber in producing tumor necrosis, compared to a standard
      bare-tipped fiber. The potential synergistic effect between thermal sensitization
      by metronidazole and interstitial laser hyperthermia (ILH)-induced tumor necrosis
      is also evaluated. BACKGROUND DATA: ILH is a minimally invasive technique for the
      treatment of colorectal liver metastases. One of the major limitations is the
      size of tissue necrosis achieved by a single optical fiber. Use of cylindrical
      diffuser-tipped fibers and thermal sensitization of tumor cells by metronidazole
      may increase the size of tumor necrosis achieved by a single optical fiber.
      MATERIALS AND METHODS: A model of colorectal cancer liver metastases in male
      inbred CBA mice was used. Laser hyperthermia was applied to tumor tissue using
      either a bare optical quartz fiber or a cylindrical diffuser-tipped fiber from a
      Medilas fibertom 4100 Nd:YAG surgical laser generator. Six hundred joules of
      energy was applied at two power settings, 5 and 10 watts, using bare- and
      diffuser-tipped fibers, respectively. The extent of necrosis was assessed by
      histological techniques. A similar study with three experimental groups was
      treated with 300 J of applied energy. Extent of immediate tumor necrosis was
      compared to that seen 24 h after ILH treatment. The third group, which had been
      treated with intraperitoneal metronidazole prior to ILH, was also assessed for
      tumor necrosis after 24 h and results compared with both the previous groups.
      RESULTS: ILH delivered using a cylindrical diffuser-tipped fiber resulted in a
      significantly larger diameter of tumor necrosis when compared to a bare-tipped
      fiber, for a given amount of applied energy. The differences were more
      significant at higher power settings. Six hundred joules of energy applied by ILH
      using a bare-tipped fiber at 5 and 10 watts produced 6.7 +/- 1.1 mm and 5.9 +/-
      0.6 mm diameter of tumor necrosis, respectively. At equivalent settings, the
      diffuser-tipped fiber produced 7.7 +/- 1.0 mm and 8.1 +/- 0.6 mm diameter of
      tumor necrosis (p = 0.02 and p < 0.001). Using a diffuser-tipped fiber and an
      applied energy of 300 J delivered at 5 watts power, mean diameter of tumor
      necrosis immediately after treatment was 6.7 +/- 1.1 mm and after 24 h 7.9 +/-
      1.3 mm (p = 0.006). Mean diameter of tumor necrosis 24 h after ILH in animals
      treated with metronidazole was 8.3 +/- 1.9 mm (p = 0.11). CONCLUSION: Diffuser
      tipped optical fiber appears to significantly increase the diameter of ILH
      induced tumor necrosis compared to the bare fiber. In contrast to the bare fiber,
      it enables the application of laser energy using higher power settings without
      compromising the diameter of tumor necrosis achieved. In animals treated with
      metronidazole, a trend towards increased tumor destruction at the tumor-host
      interface was seen on histolopathology. In addition, a trend towards increased
      diameter of tumor necrosis was also seen; however, statistical significance was
      not achieved.

PMID- 12206715
TI  - Oxidation-triggered c-Jun N-terminal kinase (JNK) and p38 mitogen-activated
      protein (MAP) kinase pathways for apoptosis in human leukaemic cells stimulated
      by epigallocatechin-3-gallate (EGCG): a distinct pathway from those of chemically
      induced and receptor-mediated apoptosis.
AB  - We investigated intracellular signalling pathways for apoptosis induced by
      epigallocatechin-3-gallate (EGCG) as compared with those induced by a toxic
      chemical substance (etoposide, VP16) or the death receptor ligand [tumour
      necrosis factor (TNF)]. EGCG as well as VP16 and TNF induced activation of two
      apoptosis-regulating mitogen-activated protein (MAP) kinases, namely c-Jun N
      terminal kinase (JNK) and p38 MAP kinase, in both human leukaemic U937 and OCI
      AML1a cells. In U937 cells, the apoptosis and activation of caspases-3 and -9
      induced by EGCG but not VP16 and TNF were inhibited with SB203580, a specific
      inhibitor of p38, while those induced by EGCG and VP16 but not TNF were inhibited
      with SB202190, a rather broad inhibitor of JNK and p38. In contrast, the EGCG
      induced apoptosis in OCI-AML1a cells was resistant to SB203580 but not to
      SB202190. Unlike TNF, EGCG did not induce the activation of nuclear factor-kappaB
      but rather induced the primary activation of caspase-9. N -Acetyl-L-cysteine
      (NAC) almost completely abolished apoptosis induced by EGCG under conditions in
      which the apoptosis induced by VP16 or TNF was not affected. The JNK/p38
      activation by EGCG was also potently inhibited by NAC, whereas those by VP16 and
      TNF were either not or only minimally affected by NAC. In addition,
      dithiothreitol also suppressed both apoptosis and JNK/p38 activation by EGCG, and
      EGCG-induced activation of MAP kinase kinase (MKK) 3/6, MKK4 and apoptosis
      regulating kinase 1 (ASK1) was suppressed by NAC. Dominant negative ASK1, MKK6,
      MKK4 and JNK1 potently inhibited EGCG-induced cell death. EGCG induced an
      intracellular increase in reactive oxygen species and GSSG, both of which were
      also inhibited by NAC, and the decreased synthesis of glutathione rendered the
      cell susceptible to EGCG-induced apoptosis. Taken together these results strongly
      suggest that EGCG executed apoptotic cell death via an ASK1, MKK and JNK/p38
      cascade which is triggered by NAC-sensitive intracellular oxidative events in a
      manner distinct from chemically induced or receptor-mediated apoptosis.

PMID- 12206721
TI  - A comparative study of microleakage through enamel and cementum after laser
      Er:YAG instrumentation in class V cavity obturations, using scanning electron
      microscopy.
AB  - OBJECTIVE: The purpose of this study was to use scanning electron microscopy
      (SEM) in order to compare the surfaces of cavities prepared using laser with
      those prepared conventionally, and to measure the degree of leakage through both
      enamel and cementum. MATERIALS AND METHODS: We prepared 135 class V cavities and
      divided them randomly into three groups: laser-treated (group A), laser-treated,
      and acid-etched (group B) and rotary instrumented (group C). RESULTS: On
      analyzing the tooth enamel, the amount of leakage was found to be similar in
      groups A and B, whilst the samples in the group C were more prone to leakage. On
      analyzing the cementum, the group C samples appeared to display surfaces that
      were more conducive to the adhesion of the materials used in obturation (although
      this difference was not strictly significant), and this might have provoked the
      relatively low levels of leakage. CONCLUSION: The use of acid etching in
      conjunction with both conventional and laser cavity preparation improves the
      adhesion of the materials used in obturation to enamel surfaces.

PMID- 12206722
TI  - Application of holmium:YAG laser in epiduroscopy: extended practicabilities in
      the treatment of chronic back pain syndrome.
AB  - OBJECTIVE: Minimally invasive and endoscopic techniques offer advantages in the
      treatment of chronic back pain syndrome and may provide for expanded indications
      and visualization. Epiduroscopy for the visualization of the epidural space still
      is burdened with technical problems. The mechanical instruments now available,
      coupled with the narrow working canal, result in marked limitations. The aim of
      this study was to assess the possibilities and technical requisites for the use
      of the holmium:YAG laser in lumbar epiduroscopy. BACKGROUND DATA: Epiduroscopy
      has been used for visualization of the lumbar epidural space since the 1930s.
      Studies have been performed to evaluate the effects and possibilities of
      epiduroscopy in chronic back pain. Most of them only describe the anatomical
      aspects. MATERIALS AND METHODS: Forty-seven patients were epiduroscopied and
      treated, for findings of corresponding epidural adhesions, with the holmium:YAG
      laser. The examinations concentrated on the general applicability of the
      holmium:YAG laser in epiduroscopy and the technical parameters necessary for this
      procedure. The clinical evaluation of therapy was made prospectively in
      comparison with the preoperative status and compared to already recorded groups
      in previous studies. RESULTS: Bending behavior without negative impact of the
      epiduroscope was only attained with laser fibers less than 300 microm, so a fiber
      with a diameter of 265 microm was used as the standard. The minimum energy output
      of the laser required for an adequate ablative effect was 0.8 J at a frequency of
      8 Hz. The total energy output was 0.256-1.4 kJ. Complications did not occur
      intraoperatively nor following the procedure. The follow-up examinations showed
      no deterioration of the complaints in any patient. There was no occurrence of
      relevant laser-related edemas or adhesions. The proportion of painful conditions
      that could be positively influenced corresponded to that in a control group
      treated only by mechanical means. CONCLUSION: The results show that the
      holmium:YAG laser considerably expands therapeutic possibilities and aids in
      solving the technical problems of epiduroscopy. No negative effects occurred when
      the laser is used.

PMID- 12206723
TI  - Er:YAG laser versus Blue Peel in the treatment of photoaging hands.
AB  - OBJECTIVE: This study aims at comparing the effects of Er:YAG laser and Blue Peel
      on the treatment of photoaged hands. BACKGROUND DATA: The face and hands are
      constantly being exposed to sunlight, which causes early skin aging and damage.
      Currently, there are many studies showing how to deal with photoaging of the
      face; however, very few have investigated treatment of photoaging of the hands,
      whose skin properties differ from the face. MATERIALS AND METHODS: We studied the
      effects (edema, erythema, temperature, reepithelialization) of laser and Blue
      Peel on the hands of 22 patients. The follow-up was 3 months. RESULTS: Edema,
      erythema, and temperature were more intense in the Er:YAG group during the early
      postoperative days, but those clinical parameters became similar to the ones
      observed in the Blue Peel group over time. Forty-five percent of the patients
      considered the results of Er:YAG treatment excellent, while 16.67% rated the
      treatment with Blue Peel as excellent. CONCLUSION: Both methods showed very good
      clinical results, but Er:YAG laser treatment satisfied the patients the most.

PMID- 12206724
TI  - Effects of Nd:YAG and Er:YAG lasers on the sealing of root canal fillings.
AB  - OBJECTIVE: The ability of the laser irradiation to promote the cleaning and
      disinfection of the radicular canal system has become this type of treatment in a
      viable and real alternative in endodontics. The purpose of this study was to
      evaluate the apical marginal sealing of root canal fillings after the irradiation
      with the laser of Nd:YAG or of Er:YAG. MATERIALS AND METHODS: Forty-two human,
      extracted single-rooted teeth had their crowns sectioned and the root canals
      prepared with a no. 70 K-file. Then, they were dried and divided into three
      groups according to canal wall treatment: group 1: the canals were filled with
      EDTA for 3 min, followed by irrigation with 1% sodium hypochlorite solution;
      group 2: the canal walls were irradiated with Nd:YAG laser; and group 3: the
      canal walls were irradiated with Er:YAG laser. Afterwards, the root canals were
      obturated by the lateral condensation technique. The roots were externally
      waterproof, except in the apical foramen and immersed in 2% methylene blue
      aqueous solution during 48 hours. RESULTS: The results showed that the largest
      infiltrations happened in the group 3-Er:YAG (7.3 mm), proceeded by the group 1
      EDTA (1.6 mm) and by the group 2-Nd:YAG (0.6 mm). The group Er:YAG differed
      statistically of the others (p < 0.05). CONCLUSION: It was concluded that the
      Er:YAG laser intracanal irradiation previously to the root canal filling must be
      used with caution until future research is define the best parameters for it's
      use.

PMID- 12206725
TI  - Assessment of the behavior of myofibroblasts on scalpel and CO(2) laser wounds:
      an immunohistochemical study in rats.
AB  - OBJECTIVE: The aims of this study were to quantitative and statistically assess
      the presence of myofibroblasts on both conventional and CO(2) laser wounds.
      BACKGROUND DATA: Wound contraction of both traumatic and surgical origin may
      reduce or limit the function of the tissue. Myofibroblasts are cells involved in
      the process of wound contraction, which is smaller in CO(2) laser wounds.
      MATERIALS AND METHODS: Thirty-two animals (rattus norvegicus) were divided into
      four groups and treated using either the CO(2 )laser (groups 1 and 2) or
      conventional scalpel (groups 3 and 4). The animals were sacrificed eight days
      post-operatively (groups: 1 and 3) and 14 days after surgery (groups: 2 and 4).
      The specimens were routinely processed to wax and stained with alpha-smooth
      muscle actin (alpha SMA) and analyzed under light microscopy (40x) using a
      calibrated eyepiece and a graticule. Two standard areas around the wound of each
      slide were selected and used to count the number of myofibroblasts present.
      RESULTS: The results of this study show that it is possible to determine the
      number of myofibroblasts present in wounds produced by the laser or the scalpel
      at both eight and 14 days after surgery. However the number of myofibroblasts at
      day eight was significantly higher than at day 14 (laser, p = 0.007 and scalpel,
      p = 0.001). The number of cells present in group 3 was significantly higher than
      in group 1 (p = 0.001). However on the 14th day there was no such difference (p =
      0.072). CONCLUSION: It is concluded that the small number of myofibroblasts at
      day eight after wounding with the CO(2) laser may be the reason that contraction
      on this wound is smaller than the one observed in conventional surgery.

PMID- 12206727
TI  - Laser literature watch.

PMID- 12206728
TI  - New Highlights in Dermatovenerology. Opatija, Croatia, May 16-19, 2002.
      Abstracts.

PMID- 12206738
TI  - [The everyday value. Urinary tract infection in children].

PMID- 12206739
TI  - [Role of direct radionuclide cystography and renal study by dimercaptosuccinic
      acid (DMSA) in the diagnosis and follow-up of vesicoureteral reflux].
AB  - AIM: To evaluate the role of isotopic studies in the diagnosis and follow-up of
      vesicoureteral reflux (VUR) and to present the results of our current protocol.
      MATERIAL AND METHODS: Forty three patients with VUR were retrospectively studied
      with a mean follow-up of 43 years (1-11 years). VUR was diagnosed by voiding
      cystourethrography and followed-up by direct radionuclide cystography. During the
      follow-up all patients were studied by means of renal DMSA scintigraphy (21 were
      also studied during the acute phase of febrile urinary tract infection). RESULTS:
      Eighty three renal units were examined. Voiding cystourethrography was positive
      for VUR in 49 renal units (59%; 8 grade I, 18 grade II, 15 grade III, and 8 grade
      IV). During the follow-up, direct radionuclide cystography showed decrease or
      disappearance of VUR in 29 renal units (35%; 4 grade I, 16 grade II, 7 grade III,
      and 2 grade IV). DMSA studies performed during the follow-up showed cortical
      lesions in 17 renal units (5 with VUR grade II, 7 with grade III, and 5 grade
      IV). Nine of 21 patients examined by DMSA during the acute phase of febrile
      urinary tract infection showed cortical damage (43%), and 6 of them (67%)
      progressed to cortical lesion in the follow-up DMSA. CONCLUSIONS: The present
      protocol allows for the correct diagnosis and control of VUR, the early detection
      of acute renal damage, and the control of its evolution.

PMID- 12206740
TI  - [Pulmonary activity in sarcoidosis: 67Ga uptake quantification and plasma
      determination of 1,25-dihydroxyvitamin D)].
AB  - AIM: The aim of our study was to produce a quantitative determination of Ga-67
      pulmonary intake and correlate it with plasma levels of calcitriol. MATERIAL AND
      METHODS: A prospective study was conducted, and included 65 patients (29 female,
      36 male) referred to our section due to suspected sarcoidosis or fibrosis of the
      lungs. Gammagraphic images were obtained after injecting Ga-67 citrate, and
      vitamin D was determined by IRMA method. The final diagnosis led to 4 groups of
      patients: 26 with active sarcoidosis; 5 with inactive sarcoidosis (4 with a
      previous gammagraphic study, included in the previous group); 8 with fibrosis of
      the lungs; and 30 patients with no demonstrable pathology following
      medical/instrumental examination. For the quantitative analysis, areas of
      interest were drawn around each lung, together with another region in soft tissue
      of the right shoulder (background). The geometric mean for each region was
      calculated, as well as the Ga intake rate (InGa = [lung activity
      background]/background). RESULTS: Significant differences were found (p<0.01)
      when comparing each group's InGa, with the highest values occurring in the active
      sarcoidosis group. No significant differences were found when comparing plasma
      levels of calcitriol. No significant correlation was demonstrated between hormone
      and InGa rates. CONCLUSIONS: InGa would seem to be a useful parameter for
      assessing inflammatory activity in the parenchyma of the lungs. Perhaps as a
      result of their variability, plasma concentrations of the active vitamin D
      metabolite have a limited role in this assessment.

PMID- 12206741
TI  - [Check-ups with brain SPECT in electroconvulsive therapy in patients with severe
      drug-resistant depressive episodes and Parkinson's disease].
AB  - We have studied three women (66,72 and 72 years) with Parkinson's disease of 11,
      6 and 21 years of evolution and drug-resistant severe depressive episodes treated
      with electroconvulsive therapy (ECT). We have performed a brain SPECT (99mTc
      HMPAO) before and after the ECT. The clinical improvement of the severe
      depressive episodes were measured using the Hamilton score. The first patient did
      not experience any clinical improvement (Hamilton score 42 to 42). In this
      patient the brain SPECT before treatment presented a reduced perfusion in the
      posterior parietal region, anterior cingulate cortex and medial frontal and
      parietal cortex. After the treatment, the brain SPECT did not present significant
      variations. The second patient presented a moderate clinical improvement
      (Hamilton score 46 to 36) and also presented moderate improvement in the
      neurological symptoms. The brain SPECT before the treatment showed reduced
      perfusion in the left temporal cortex and medium-posterior parietal cortex. After
      the treatment, it also did not reflect significant variations. The third patient
      experienced a very good response to the ECT sessions (Hamilton score 45 to 10)
      and also an improvement regarding the neurological symptoms. This patient
      presented a reduced perfusion in the medium-posterior parietal regions in the
      brain SPECT performed before the treatment; these regions presented a moderate
      improvement in the brain SPECT performed after the treatment. The patient who
      presented a significant neurological and psychiatric improvement also presented
      an improvement in the perfusion of the decreased areas in the brain SPECT and
      showed fewer alterations in the baseline brain SPECT compared with the others.
      The brain SPECT could have a prognostic (and confirmation) role regarding
      clinical improvement induced by ECT in resistant depression in Parkinson's
      disease. ECT is an alternative in treatment of severe depressive drug-resistant
      episodes associated to the Parkinson's disease.

PMID- 12206742
TI  - [99mTc-labelled antigranulocyte anibody fragment Fab scintigraphy (sulesomab,
      leukoscan) and three-phase bone scintigraphy in the study of painful hip and knee
      prosthesis].
AB  - We aim to assess the diagnostic utility of the combination of a three phase bone
      scintigraphy (3FBS) and scintigraphy with Fab'antigranulocyte fragments-99mTc
      (Sulesomab, Leukoscan) in patients with painful joint replacements. We studied 29
      patients (22 women and 7 men with mean age 64 years) with knee (15) and hip (14)
      prosthesis. Scintigraphy was performed with a Siemens Orbiter 75 gammacamera with
      all purpose collimator. 3FBS was performed as usual with 740 MBq of MDP-99mTc.
      Sulesomab images were obtained at 1 and 4 hours following injection of 740 MBq,
      with 300,000 cts per view (knee) and 500,000 cts per view (hip). Both
      scintigraphic studies were interpreted visually by two nuclear medicine
      physicians with a 0, 1, 2, 3 score corresponding to normal or mild, moderate or
      intense hyperactivity respectively. Interpretation criteria for bone infection
      was Sulesomab uptake grade 2 or 3 in a moderate or large sized area, with
      congruent hyperactivity on the bone scan. Grade 1 uptake with Sulesomab was
      considered nonspecific associated to nonseptic conditions. The frequent pattern
      of uptake in synovial femoral tissue (cap shape sign) in knee prosthesis was
      considered nonspecific. Diagnostic confirmation procedures were surgery and
      culture (9) and follow-up (20). All six septic joints were correctly identified.
      A false positive result was obtained in a case of mechanical loosening in the
      knee. Negative studies were very helpful in the exclusion of infection. Our
      conclusion is that sensitivity is high, 100%, and that a normal or grade 1
      Sulesomab image makes the presence of infection improbable.

PMID- 12206743
TI  - [Intense uptake of 99mTc-MDP in primary abdominal neuroblastoma].

PMID- 12206744
TI  - [99mTc-HDP uptake by soft tissue secondary to hypercalcemia].

PMID- 12206745
TI  - [It is the erythrocytic volume and not the blood volume that is directly measured
      after red blood cells are labeled with 51Cr].

PMID- 12206747
TI  - [Myocardial positron emission tomography (PET) with fluorodeoxyglucose-18F].

PMID- 12206748
TI  - [Positron emission tomography (PET) in clinical oncology [Part III]].

PMID- 12206749
TI  - [A proposal for the rational use of the PET in oncology].
AB  - OBJECTIVE: This study aims to develop a Clinical Practice Guide for the rational
      use of the Positron Emission Tomography (PET) in Oncology, that makes it possible
      to approach the real existence of demand in the public health care service of
      Andalucia, by limiting the clinical indications, using criteria based on the
      existence of sufficient scientific evidence on the effectiveness and clinical
      impact of PET. METHOD: The consensus technique was used to elaborate the Guide,
      gathering a group of nuclear medicine experts. Prior to this a systematic
      research of the scientific literature was carried out, using strict criteria for
      the selection of the articles, such as the evaluation of the epidemiological
      data, work methodology, clinical and pathological diagnosis, gold standard
      references and statistical analysis. In each pathology group, the existence of
      alternative non-invasive diagnostic techniques was assessed, comparing its
      effectiveness and clinical impact with the PET, and the existence of useful
      treatments correlated with the results of the examination was also evaluated.
      When it was possible, we evaluated the cost-effectiveness of the PET. Finally,
      the cost-effectivity of the technique was assessed and the limitation of present
      and future resources and the economical costs arising from the PET costs and
      introduction were evaluated. RESULTS AND CONCLUSIONS: It was considered that the
      PET was indicated in the following clinical conditions: 1: Assessment of
      Colorectal Cancer recurrence in patients with increased levels of tumor markers
      and negative morphological imaging techniques. Suspicion of isolated resectable
      recurrence. 2: Restaging in patients with high risk melanoma. 3: Differential
      diagnosis of solitary pulmonary nodules. 4: Staging of non-small cell bronchial
      carcinoma. 5: Staging and detection of recurrences of lymphomas. 6: Restaging of
      head and neck cancer with possibilities of curative treatment. 7: Diagnosis of
      recurrences in differentiated thyroid cancer in patients with increased plasma
      levels of thyroglobulin and negative radioiodine scintiscan. 8: Staging and
      follow-up of medullary thyroid carcinoma. 9: Differential diagnosis between
      recurrent tumor and scar or radionecrosis in brain tumors.

PMID- 12206751
TI  - Complete characterisation of Tn5530 from Burkholderia cepacia strain 2a (pIJB1)
      and studies of 2,4-dichlorophenoxyacetate uptake by the organism.
AB  - The complete genetic characterisation of Tn5530 in Burkholderia cepacia strain 2a
      (pIJB1) has been accomplished, indicating that it is a Tn3-like transposon with a
      complex structure bearing operons for the catabolism of 2,4
      dichlorophenoxyacetate (2,4-D) and malonate. Tn5530 is terminated at both ends by
      the IS1071::IS1471 element and the 2,4-D- and malonate-dissimilatory operons are
      separated by a region encoding a putA and lrp gene and a gene encoding a chloride
      channel protein. The chloride channel protein may have a role in the expulsion of
      chloride ions liberated by the dissimilation of 2,4-D. In addition, a putative
      transposase with a high level of sequence similarity to those of plasmid pGH1
      from Xanthomonas campestris pv. vesicatoria and Pseudomonas syringae pv.
      glycinea, and a transcription factor similar to those of the TetR family with low
      but significant levels of sequence similarity to those identified in a number of
      other organisms was observed. The entire Tn5530 sequence length, including the
      IS1071::IS1471 elements, was found to be 40,956bp, and pIJB1 was replicon-typed
      and otherwise characterised as being of the IncP-1beta subgroup, bearing merA and
      merD genes conferring resistance to mercuric chloride. The rate of uptake of 2,4
      D by B. cepacia strain 2a was observed to proceed more readily at acid pH,
      suggesting involvement of the undissociated form of the compound. Uptake did not
      show saturation kinetics, was concentration-dependent, and appeared to occur in
      two stages; an initial accumulation followed by a linear second phase. Uptake
      could be inhibited by sodium azide but not by arsenate, N,N(')
      dicyclohexylcarbodi-imide (DCCD) or carbonylcyanide m-chlorophenyl-hydrazone
      (CCCP) suggesting that it is not energy-dependent.

PMID- 12206752
TI  - Replication of a linear mini-chromosome with terminal inverted repeats from the
      Kluyveromyces lactis linear DNA plasmid k2 in the cytoplasm of Saccharomyces
      cerevisiae.
AB  - The k1 and k2 linear DNA plasmids of Kluveromyces lactis replicate in the
      cytoplasm under the control of plasmid-encoded genes. These plasmids can also
      replicate autonomously in the cytoplasm of mitochondrial DNA-deficient strains of
      Saccharomyces cerevisiae. Essential for replication are plasmid-specific terminal
      inverted repeats (TIRs) to which a terminal protein (TP) is attached at the 5'
      ends. A plasmid was constructed with k2 TIRs in opposite orientations and with a
      selectable marker (URA3) under the control of k1UCS2 (upstream conserved sequence
      2, the promoter of k1 open reading frame 2) in between the TIRs. Transformation
      of k1- and k2-containing S. cerevisiae with a fragment generated by releasing the
      TIR-flanked fragment from the plasmid by restriction digestion was very
      efficient, despite the absence of a TP. Transformation was also achieved with a
      fragment generated by PCR. Southern blotting demonstrated that transformants
      contained multiple copies of DNA fragments with the same size as the transforming
      DNA, supporting the hypothesis that these were replicating linear mini
      chromosomes. The high frequency of transformation strongly suggests that these
      mini-chromosomes readily replicate supported by k2. Derivatives with a
      heterologous gene, firefly luciferase (LUC), expressed luciferase at high levels
      provided the gene was adjacent to a cytoplasmic plasmid promoter (k2UCS5).

PMID- 12206753
TI  - Analysis and characterization of the IncFV plasmid pED208 transfer region.
AB  - pED208 is a transfer-derepressed mutant of the IncFV plasmid, F(0)lac, which has
      an IS2 element inserted in its traY gene, resulting in constitutive
      overexpression of its transfer (tra) region. The pED208 transfer region, which
      encodes proteins responsible for pilus synthesis and conjugative plasmid
      transfer, was sequenced and found to be very similar to the F tra region in terms
      of its organization although most pED208 tra proteins share only about 45% amino
      acid identity. All the essential genes for F transfer had homologs within the
      pED208 transfer region with the exception of traQ, which encodes the chaperone
      for stable F-pilin expression. F(0)lac appears to have a fertility inhibition
      system different than the FinOP system of other F-like plasmids, and its transfer
      efficiency was increased in the presence of F or R100, suggesting that it could
      be mobilized by these plasmids. The F-like transfer systems specified by F, R100,
      and F(0)lac were highly specific for their cognate origins of transfer (oriT) as
      measured by their abilities to mobilize chimeric oriT-containing plasmids.

PMID- 12206754
TI  - Characterisation and genetic organisation of a 24-MDa plasmid from the Brazilian
      Purpuric Fever clone of Haemophilus influenzae biogroup aegyptius.
AB  - Strains of Haemophilus influenzae biogroup aegyptius causing septicaemia were
      identified in Brazil in the 1980s, causing the life-threatening illness of
      Brazilian Purpuric Fever (BPF). The strains were found to fall into a single
      clonal group, the BPF clone, characterised by their possession of the
      approximately 24MDa "3031" plasmid. In this work we report the characterisation
      and genetic organisation of this plasmid. Analysis of the gene content of what
      appears to be a typical broad host range conjugative plasmid, its presence in non
      BPF strains as revealed by Southern hybridisation, and the recent discovery of
      plasmid-lacking BPF strains, has led us to conclude that it is unlikely to play a
      critical role in bacterial virulence. Establishing its entire sequence has
      nonetheless been an important step on the road to delineating, by comparison of
      BPF and non-BPF strains, chromosomal genetic loci that are involved in the
      special virulence of the BPF clone.

PMID- 12206755
TI  - Polyadenylation can regulate ColE1 type plasmid copy number independently of any
      effect on RNAI decay by decreasing the interaction of antisense RNAI with its
      RNAII target.
AB  - Replication of ColE1-type plasmids is regulated by RNAI, an antisense RNA that
      interacts with the replication pre-primer, RNAII. Exonucleolytic attack at the 3'
      end of RNAI is impeded in pcnB mutant bacteria, which lack poly(A) polymerase I
      the principal RNA polyadenylase of E. coli; this leads to accumulation of an RNAI
      decay intermediate (RNAI(-5)) and dramatic reduction of the plasmid copy number.
      Here, we report that polyadenylation can also affect RNAI-mediated control of
      plasmid DNA replication by inhibiting interaction of RNAI(-5) with RNAII. We show
      that mutation of the host pcnB gene profoundly affects the plasmid copy number,
      even under experimental conditions that limit the effects of polyadenylation on
      RNAI(-5) decay. Moreover, poly(A) tails interfere with RNAI/RNAII interaction in
      vitro without producing any detectable alteration of RNAI secondary structure.
      Our results establish the existence of a previously undetected mechanism by which
      RNA polyadenylation can control plasmid copy number.

PMID- 12206756
TI  - Sequence analysis and characterization of plasmid pSFD10 from Salmonella
      choleraesuis.
AB  - The nucleotide sequence of a small plasmid, designated pSFD10, is isolated from
      the vaccine strain Salmonella choleraesuis C500 in China, has been determined.
      This plasmid is 4091 bp long with a total G+C content of 51.4%, which is in the
      range of Salmonella genomic DNA. Analysis of the complete nucleotide sequence
      reveals that pSFD10 has a high degree of similarity to ColE1-type plasmid, having
      the possible cer and rom genes, and a putative mobilization origin of ColE1-type.
      Plasmid pSFD10 possesses six main open reading frames (ORFs), five of which have
      a very high degree of amino acid identity to ColE1-type plasmid gene products
      involved in mobilization and copy number control. The other ORF (ORF6) encodes a
      putative protein, which has 49% homology to the invasion plasmid antigen J
      protein (IpaJ) secreted by the type III secretion apparatus of Shigella flexneri.
      In addition, pSFD10 belongs to a different incompatibility group than ColE1-type
      and pMB1-type to which it is related. Plasmid pSFD10 can be mobilized by the
      plasmid RP4 in E. coli.

PMID- 12206757
TI  - Prevotella intermedia native plasmid can be mobilized by an Escherichia coli
      conjugal IncP plasmid.
AB  - We have determined the nucleotide sequence of a small Prevotella intermedia
      cryptic plasmid, pYHBi1, which consisted of sequences that were highly homologous
      to the amino acid sequence of the replication and mobilization proteins found in
      related organisms. We have also demonstrated that chimeric plasmids derived from
      this P. intermedia native plasmid can be mobilized between Escherichia coli
      strains by using a broad-host-range E. coli conjugative plasmid, IncP plasmid
      RP4. The results suggest that pYHBi1 possesses gene(s) responsible for conjugal
      transfer.

PMID- 12206758
TI  - Chromosomal sequences from Klebsiella pneumoniae flank the SHV-5 extended
      spectrum beta-lactamase gene in pACM1.
AB  - The nucleotide sequence was determined for Anon 13, a 1250-bp SmaI fragment
      located approximately 2.8 kb downstream from bla(SHV-5) in pACM1. Anon 13 is 99%
      identical to a segment of the unpublished sequence of the Klebsiella pneumoniae
      chromosome. Genes of the K. pneumoniae sequence are undefined, but conceptual
      amino acid translations of two ORFs in Anon 13 are homologous to L-fuculose-1
      phosphate aldolase (FucA) and a conserved hypothetical protein present in the
      chromosomes of several species of bacteria. In addition, restriction mapping
      indicates that the region of homology between the K. pneumoniae chromosome and
      pACM1 is as least 7.9 kb and includes both Anon 13 and bla(SHV). These
      observations demonstrate the chromosomal origin of the bla(SHV-5) on pACM1.

PMID- 12206759
TI  - One fold with many functions: the evolutionary relationships between TIM barrel
      families based on their sequences, structures and functions.
AB  - The eightfold (betaalpha) barrel structure, first observed in triose-phosphate
      isomerase, occurs ubiquitously in nature. It is nearly always an enzyme and most
      often involved in molecular or energy metabolism within the cell. In this review
      we bring together data on the sequence, structure and function of the proteins
      known to adopt this fold. We highlight the sequence and functional diversity in
      the 21 homologous superfamilies, which include 76 different sequence families. In
      many structures, the barrels are "mixed and matched" with other domains
      generating additional variety. Global and local structure-based alignments are
      used to explore the distribution of the associated functional residues on this
      common structural scaffold. Many of the substrates/co-factors include a phosphate
      moiety, which is usually but not always bound towards the C-terminal end of the
      sequence. Some, but not all, of these structures, exhibit a structurally
      conserved "phosphate binding motif". In contrast metal-ligating residues and
      catalytic residues are distributed along the sequence. However, we also found
      striking structural superposition of some of these residues. Lastly we consider
      the possible evolutionary relationships between these proteins, whose sequences
      are so diverse that even the most powerful approaches find few relationships, yet
      whose active sites all cluster at one end of the barrel. This extreme example of
      the "one fold-many functions" paradigm illustrates the difficulty of assigning
      function through a structural genomics approach for some folds.

PMID- 12206760
TI  - The mechanism of transcriptional activation by the topologically DNA-linked
      sliding clamp of bacteriophage T4.
AB  - Three viral proteins participate directly in transcription of bacteriophage T4
      late genes: the sigma-family protein gp55 provides promoter recognition, gp33 is
      the co-activator, and gp45 is the activator of transcription; gp33 also represses
      transcription in the absence of gp45. Transcriptional activation by gp45, the
      toroidal sliding clamp of the T4 DNA polymerase holoenzyme, requires assembly at
      primer-template junctions by its clamp loader. The mechanism of transcriptional
      activation has been analyzed by examining rates of formation of open promoter
      complexes. The basal gp55-RNA polymerase holoenzyme is only weakly held in its
      initially formed closed promoter complex, which subsequently opens very slowly.
      Activation ( approximately 320-fold in this work) increases affinity in the
      closed complex and accelerates promoter opening. Promoter opening by gp55 is also
      thermo-irreversible: the T4 late promoter does not open at 0 degrees C, but once
      opened at 30 degrees C remains open upon shift to the lower temperature. At a
      hybrid promoter for sigma(70) and gp55-holoenzymes, only gp55 confers thermo
      irreversibility of promoter opening. Interaction of gp45 with a C-terminal
      epitope of gp33 is essential for the co-activator function of gp33.

PMID- 12206761
TI  - Crystal structure and anion binding in the prokaryotic hydrogenase maturation
      factor HypF acylphosphatase-like domain.
AB  - [NiFe]-hydrogenases require a set of complementary and regulatory proteins for
      correct folding and maturation processes. One of the essential regulatory
      proteins, HypF (82kDa) contains a N-terminal acylphosphatase (ACT)-like domain, a
      sequence motif shared with enzymes catalyzing O-carbamoylation, and two zinc
      finger motifs similar to those found in the DnaJ chaperone. The HypF
      acylphosphatase domain is thought to support the conversion of carbamoylphosphate
      into CO and CN(-), promoting coordination of these ligands to the hydrogenase
      metal cluster. It has been shown recently that the HypF N-terminal domain can
      aggregate in vitro to yield fibrils matching those formed by proteins linked to
      amyloid diseases. The 1.27A resolution HypF acylphosphatase domain crystal
      structure (residues 1-91; R-factor 13.1%) shows a domain fold of
      betaalphabetabetaalphabeta topology, as observed in mammalian acylphosphatases
      specifically catalyzing the hydrolysis of the carboxyl-phosphate bonds in
      acylphosphates. The HypF N-terminal domain can be assigned to the ferredoxin
      structural superfamily, to which RNA-binding domains of small nuclear
      ribonucleoproteins and some metallochaperone proteins belong. Additionally, the
      HypF N-terminal domain displays an intriguing structural relationship to the
      recently discovered ACT domains. The structures of different HypF acylphosphatase
      domain complexes show a phosphate binding cradle comparable to the P-loop
      observed in unrelated phosphatase families. On the basis of the catalytic
      mechanism proposed for acylphosphatases, whereby residues Arg23 and Asn41 would
      support substrate orientation and the nucleophilic attack of a water molecule on
      the phosphate group, fine structural features of the HypF N-terminal domain
      putative active site region may account for the lack of acylphosphatase activity
      observed for the expressed domain. The crystallographic analyses here reported
      were undertaken to shed light on the molecular bases of inactivity, folding,
      misfolding and aggregation of the HypF N-terminal acylphosphatase domain.

PMID- 12206762
TI  - The role of the alpha2 chain in the stabilization of the collagen type I
      heterotrimer: a study of the type I homotrimer in oim mouse tissues.
AB  - We have previously reported that the fragility of skin, tendon and bone from the
      oim mouse is related to a significant reduction in the intermolecular cross
      linking. The oim mutation is unlikely to affect the efficacy of the lysyl
      oxidase, suggesting that the defect is in the molecule and fibre. We have
      therefore investigated the integrity of both the oim collagen molecules and the
      fibre by differential scanning calorimetry. The denaturation temperature of the
      oim molecule in solution and the fibre from tail tendon were found to be higher
      than the wild-type by 2.6deg.C and 1.9deg.C, respectively. With the loss of the
      alpha2 chain, the hydroxyproline content of the homotrimer is higher than the
      heterotrimer, which may account for the increase. There is a small decrease in
      the enthalpy of the oim fibres but it is not significant, suggesting that the
      amount of disorder of the triple-helical molecules and of the fibres is small and
      involves only a small part of the total bond energy holding the helical structure
      together. The difference in denaturation temperature of the skin collagen
      molecules (t(m)) and fibres (t(d)) is significantly lower for the oim tissues,
      19.9deg.C against 23.1deg.C, indicating reduced molecular interactions and hence
      packing of the molecules in the fibre. Computation of the volume fraction of the
      water revealed that the interaxial separation of the oim fibres was indeed
      greater, increasing from 19.6A to 21.0A. This difference of 1.4A, equivalent to a
      C-C bond, would certainly decrease the ability of the telopeptide aldehyde to
      interact with the epsilon -amino group from an adjacent molecule and form a cross
      link. We suggest, therefore, that the reduction of the cross-linking is due to
      increased water content of the fibre rather than a distortion of the molecular
      structure. The higher hydrophobicity of the alpha2 chain appears to play a role
      in the stabilisation of heterotrimeric type I collagen, possibly by increasing
      the hydrophobic interactions between the heterotrimeric molecules, thereby
      reducing the water content and increasing the binding of the molecules in the
      fibre.

PMID- 12206763
TI  - T7 DNA helicase: a molecular motor that processively and unidirectionally
      translocates along single-stranded DNA.
AB  - DNA helicases are molecular motors that use the energy from NTP hydrolysis to
      drive the process of duplex DNA strand separation. Here, we measure the
      translocation and energy coupling efficiency of a replicative DNA helicase from
      bacteriophage T7 that is a member of a class of helicases that assembles into
      ring-shaped hexamers. Presteady state kinetics of DNA-stimulated dTTP hydrolysis
      activity of T7 helicase were measured using a real time assay as a function of
      ssDNA length, which provided evidence for unidirectional translocation of T7
      helicase along ssDNA. Global fitting of the kinetic data provided an average
      translocation rate of 132 bases per second per hexamer at 18 degrees C. While
      translocating along ssDNA, T7 helicase hydrolyzes dTTP at a rate of 49 dTTP per
      second per hexamer, which indicates that the energy from hydrolysis of one dTTP
      drives unidirectional movement of T7 helicase along two to three bases of ssDNA.
      One of the features that distinguishes this ring helicase is its processivity,
      which was determined to be 0.99996, which indicated that T7 helicase travels on
      an average about 75kb of ssDNA before dissociating. We propose that the ability
      of T7 helicase to translocate unidirectionally along ssDNA in an efficient manner
      plays a crucial role in DNA unwinding.

PMID- 12206764
TI  - Proteorhodopsin is a light-driven proton pump with variable vectoriality.
AB  - Proteorhodopsin, a homologue of archaeal bacteriorhodopsin (BR), belongs to a
      newly identified family of retinal proteins from marine bacteria, which could
      play an important role in the energy balance of the biosphere. We cloned the cDNA
      sequence of proteorhodopsin by chemical gene synthesis, expressed the protein in
      Escherichia coli cells, purified and reconstituted the protein in its functional
      active state. The photocycle characteristics were determined by time-resolved
      absorption and Fourier transform infrared (FT-IR) spectroscopy. The pH-dependence
      of the absorption spectrum indicates that the pK(a) of the primary acceptor of
      the Schiff base proton (Asp97) is 7.68. Generally, the photocycle of
      proteorhodopsin is similar to that of BR, although an L-like photocycle
      intermediate was not detectable. Whereas at pH>7 an M-like intermediate is formed
      upon illumination, at pH 5 no M-like intermediate could be detected. As the
      photocycle kinetics do not change between the acidic and alkaline state of
      proteorhodopsin, the only difference between these two forms is the protonation
      status of Asp97. This is corroborated by time-resolved FT-IR spectroscopy, which
      demonstrates that proton transfer from the retinal Schiff base to Asp97 is
      observed at alkaline pH, but the other vibrational changes are essentially pH
      independent.After reconstitution into proteoliposomes, light-induced proton
      currents of proteorhodopsin were measured in a compound membrane system where
      proteoliposomes were adsorbed to planar lipid bilayers. Our results show that
      proteorhodopsin is a light-driven proton pump with characteristics similar to
      those of BR at alkaline pH. However, at acidic pH, the direction of proton
      pumping is inverted. Complementary experiments were carried out on
      proteorhodopsin expressed heterologously in Xenopus laevis oocytes under voltage
      clamp conditions. The following results were obtained. (1) At alkaline pH,
      proteorhodopsin mediates outwardly directed proton pumping like BR. (2) The
      direction of proton pumping can be inverted, when Asp97 is protonated. (3) The
      current can be inverted by changes of the polarity of the applied voltage. (4)
      The light intensity-dependence of the photocurrents leads to the conclusion that
      the alkaline form of proteorhodopsin shows efficient proton pumping after
      sequential excitation by two photons.

PMID- 12206765
TI  - Flexibility of the rings: structural asymmetry in the DnaB hexameric helicase.
AB  - DnaB is the primary replicative helicase in Escherichia coli and the hexameric
      DnaB ring has previously been shown to exist in two states in the presence of
      nucleotides. In one, all subunits are equivalent, while in the other, there are
      two different subunit conformations resulting in a trimer of dimers. Under all
      conditions that we have used for electron microscopy, including the absence of
      nucleotide, some rings exist as trimers of dimers, showing that the symmetry of
      the DnaB hexamer can be broken prior to nucleotide binding. Three-dimensional
      reconstructions reveal that the N-terminal domain of DnaB makes two very
      different contacts with neighboring subunits in the trimer of dimers, but does
      not form a predicted dimer with a neighboring N-terminal domain. Within the
      trimer of dimers, the helicase domain exists in two alternate conformations, each
      of which can form symmetrical hexamers depending upon the nucleotide cofactor
      used. These results provide new information about the modular architecture and
      domain dynamics of helicases, and suggest, by comparison with the hexameric
      bacteriophage T7 gp4 and SV40 large T-antigen helicases, that a great structural
      and mechanistic diversity may exist among the hexameric helicases.

PMID- 12206766
TI  - Sequence plasticity in the antigen-binding site of a therapeutic anti-HER2
      antibody.
AB  - We have examined the plasticity of the antigen-combining site of a high-affinity
      antibody. In phage-displayed Fab libraries, selected CDR positions and one FR
      position of the humanized anti-Her2 antibody hu4D5 were substituted with all 20
      amino acids. Antigen-binding selections were used to enrich for high-affinity
      variants, and a large number of sequences were obtained prior to convergence of
      the selected pool to a small set of clones. As expected, sequence variability of
      the antigen-binding site is overall diminished compared to known IgG sequences;
      however, certain positions retain much higher variability than others. The
      sequence variability map of the hu4D5 binding site is compared with a map derived
      from previous alanine-scanning of the antibody. Affinities of soluble Fab
      fragments for antigen confirm that multiple variants were selected with high
      affinity for antigen, including one variant with a single point mutation that was
      about threefold improved in affinity compared to the parental hu4D5.
      Interestingly, this mutation is one of the most radical in terms of changing side
      chain chemistry (Trp for Asp) and occurs at the most plastic site as calculated
      by the Wu-Kabat variability coefficient. Thus variability mapping yields
      information about the antibody-antigen interaction that is useful and
      complementary to that obtained by alanine scanning mutagenesis.

PMID- 12206767
TI  - NMR investigation of the dynamics of tryptophan side-chains in hemoglobins.
AB  - NMR relaxation measurements of 15N spin-lattice relaxation rate (R(1)), spin-spin
      relaxation rate (R(2)), and heteronuclear nuclear Overhauser effect (NOE) have
      been carried out at 11.7T and 14.1T as a function of temperature for the side
      chains of the tryptophan residues of 15N-labeled and/or (2H,15N)-labeled
      recombinant human normal adult hemoglobin (Hb A) and three recombinant mutant
      hemoglobins, rHb Kempsey (betaD99N), rHb (alphaY42D/betaD99N), and rHb
      (alphaV96W), in the carbonmonoxy and the deoxy forms as well as in the presence
      and in the absence of an allosteric effector, inositol hexaphosphate (IHP). There
      are three Trp residues (alpha14, beta15, and beta37) in Hb A for each alphabeta
      dimer. These Trp residues are located in important regions of the Hb molecule,
      i.e. alpha14Trp and beta15Trp are located in the alpha(1)beta(1) subunit
      interface and beta37Trp is located in the alpha(1)beta(2) subunit interface. The
      relaxation experiments show that amino acid substitutions in the alpha(1)beta(2)
      subunit interface can alter the dynamics of beta37Trp. The transverse relaxation
      rate (R(2)) for beta37Trp can serve as a marker for the dynamics of the
      alpha(1)beta(2) subunit interface. The relaxation parameters of deoxy-rHb Kemspey
      (betaD99N), which is a naturally occurring abnormal human hemoglobin with high
      oxygen affinity and very low cooperativity, are quite different from those of
      deoxy-Hb A, even in the presence of IHP. The relaxation parameters for rHb
      (alphaY42D/betaD99N), which is a compensatory mutant of rHb Kempsey, are more
      similar to those of Hb A. In addition, TROSY-CPMG experiments have been used to
      investigate conformational exchange in the Trp residues of Hb A and the three
      mutant rHbs. Experimental results indicate that the side-chain of beta37Trp is
      involved in a relatively slow conformational exchange on the micro- to
      millisecond time-scale under certain experimental conditions. The present results
      provide new dynamic insights into the structure-function relationship in
      hemoglobin.

PMID- 12206768
TI  - Crystal structure of a conger eel galectin (congerin II) at 1.45A resolution:
      implication for the accelerated evolution of a new ligand-binding site following
      gene duplication.
AB  - The crystal structure of congerin II, a galectin family lectin from conger eel,
      was determined at 1.45A resolution. The previously determined structure of its
      isoform, congerin I, had revealed a fold evolution via strand swap; however, the
      structure of congerin II described here resembles other prototype galectins. A
      comparison of the two congerin genes with that of several other galectins
      suggests acceralated evolution of both congerin genes following gene duplication.
      The presence of a Mes (2-[N-morpholino]ethanesulfonic acid) molecule near the
      carbohydrate-binding site in the crystal structure points to the possibility of
      an additional binding site in congerin II. The binding site consists of a group
      of residues that had been replaced following gene duplication suggesting that the
      binding site was built under selective pressure. Congerin II may be a protein
      specialized for biological defense with an affinity for target carbohydrates on
      parasites' cell surface.

PMID- 12206769
TI  - Unfolding of a leucine zipper is not a simple two-state transition.
AB  - Temperature-induced unfolding of the leucine zipper, an alpha-helical, double
      stranded, coiled-coil, was studied by circular dichroism spectroscopy,
      spectrofluorimetry and heat capacity scanning calorimetry. It is shown that this
      process does not represent a simple two-state transition, as previously believed,
      but consists of several stages. The first transition starts at the very beginning
      of heating from 0 degrees C and proceeds with significant heat absorption and
      decrease of ellipticity. This transition does not depend on the concentration of
      protein and is sensitive to modification of the N terminus; it is therefore
      associated with unfolding or fraying of this part of the leucine zipper. The
      second transition takes place at a considerably higher temperature; it is more
      pronounced than the first one and does not depend on the concentration of
      protein, i.e. it is unimolecular. This transition is sensitive to modification of
      both termini of the leucine zipper and affects the optical properties of a
      tryptophan residue placed in the central part of the zipper. It therefore
      involves the whole dimer but does not result in its dissociation, presumably
      being associated with some repacking of the coiled-coil. This second transition
      is followed at higher temperatures by the concentration-dependent cooperative
      unfolding/dissociation of the two strands. The enthalpy and entropy of the
      temperature-induced structural changes of the leucine zipper that take place
      before its cooperative unfolding/dissociation comprises almost 40% of the total
      enthalpy and entropy of unfolding of the completely folded coiled-coil, the state
      in which it appears to be below 0 degrees C. Comparison of the total enthalpy of
      leucine zipper unfolding with that of a single-stranded alpha-helix shows that
      their temperature-dependence correlates with the extent of intramolecular non
      polar contacts and allows an assessment of the enthalpy of hydrogen bonding in
      alpha-helices, which appears to be about 3.3kJmol(-1) at 20 degrees C.

PMID- 12206770
TI  - Elastic properties of proteins: insight on the folding process and evolutionary
      selection of native structures.
AB  - We carry out a theoretical study of the vibrational and relaxation properties of
      naturally occurring proteins with the purpose of characterizing both the folding
      and equilibrium thermodynamics. By means of a suitable model, we provide a full
      characterization of the spectrum and eigenmodes of vibration at various
      temperatures by merely exploiting the knowledge of the protein native structure.
      It is shown that the rate at which perturbations decay at the folding transition
      correlates well with experimental folding rates. This validation is carried out
      on a list of about 30 two-state folders. Furthermore, the qualitative analysis of
      residues mean square displacements (shown to reproduce crystallographic data
      accurately) provides a reliable and statistically accurate method to identify
      crucial folding sites/contacts. This novel strategy is validated against clinical
      data for human immunodeficiency virus type 1 (HIV-1) protease. Finally, we
      compare the spectra and eigenmodes of vibration of natural proteins against
      randomly generated compact structures and regular random graphs. The comparison
      reveals a distinctive enhanced flexibility of natural structures accompanied by
      slow relaxation times at the folding temperature. The fact that these properties
      are connected intimately to the presence and assembly of secondary motifs hints
      at the special criteria adopted by evolution in the selection of viable folds.

PMID- 12206771
TI  - Computational de novo design, and characterization of an A(2)B(2) diiron protein.
AB  - Diiron proteins are found throughout nature and have a diverse range of
      functions; proteins in this class include methane monooxygenase, ribonucleotide
      reductase, Delta(9)-acyl carrier protein desaturase, rubrerythrin, hemerythrin,
      and the ferritins. Although each of these proteins has a very different overall
      fold, in every case the diiron active site is situated within a four-helix
      bundle. Additionally, nearly all of these proteins have a conserved Glu-Xxx-Xxx
      His motif on two of the four helices with the Glu and His residues ligating the
      iron atoms. Intriguingly, subtle differences in the active site can result in a
      wide variety of functions. To probe the structural basis for this diversity, we
      designed an A(2)B(2) heterotetrameric four-helix bundle with an active site
      similar to those found in the naturally occurring diiron proteins. A novel
      computational approach was developed for the design, which considers the energy
      of not only the desired fold but also alternatively folded structures. Circular
      dichroism spectroscopy, analytical ultracentrifugation, and thermal unfolding
      studies indicate that the A and B peptides specifically associate to form an
      A(2)B(2) heterotetramer. Further, the protein binds Zn(II) and Co(II) in the
      expected manner and shows ferroxidase activity under single turnover conditions.

PMID- 12206772
TI  - Genome-wide nuclear morphology screen identifies novel genes involved in nuclear
      architecture and gene-silencing in Saccharomyces cerevisiae.
AB  - Organisation of the cell nucleus is crucial for the regulation of gene expression
      but little is known about how nuclei are structured. To address this issue, we
      designed a genomic screen to identify factors involved in nuclear architecture in
      Saccharomyces cerevisiae. This screen is based on microscopic monitoring of
      nuclear pore complexes and nucleolar proteins fused with the green fluorescent
      protein in a collection of approximately 400 individual deletion mutants. Among
      the 12 genes identified by this screen, most affect both the nuclear envelope and
      the nucleolar morphology. Corresponding gene products are localised
      preferentially to the nucleus or close to the nuclear periphery. Interestingly,
      these nuclear morphology alterations were associated with chromatin-silencing
      defects. These genes provide a molecular context to explore the functional link
      between nuclear architecture and gene silencing.

PMID- 12206773
TI  - TraY DNA recognition of its two F factor binding sites.
AB  - F factor TraY, a ribbon-helix-helix DNA-binding protein, performs two roles in
      bacterial conjugation. TraY binds the F origin of transfer (oriT) to promote
      nicking of plasmid DNA prior to conjugative transfer. TraY also binds the P(Y)
      promoter to up-regulate tra gene expression. The two plasmid regions bound by
      TraY share limited sequence identity, yet TraY binds them with similar
      affinities. TraY recognition of the two sites was first probed using in vitro
      footprinting methods. Hydroxyl radical footprinting at both oriT and P(Y) sites
      indicated that bound TraY protected the DNA backbone bordering three adjacent DNA
      subsites. Analytical ultracentrifugation results for TraY:oligonucleotide
      complexes were consistent with two of these subsites being bound cooperatively,
      and the third being occupied at higher TraY concentrations. Methylation
      protection and interference footprinting identified several guanine bases
      contacted by or proximal to bound TraY, most located within these subsites. TraY
      affinity for variant oriT sequences with base substitutions at or near these
      guanine bases suggested that two of the three subsites correspond to high
      affinity, cooperatively bound imperfect inverted GA(G/T)A repeats. Altering the
      spacing or orientation of these sites reduced binding. TraY mutant R73A failed to
      protect two symmetry-related oriT guanine bases in these repeats from
      methylation, identifying possible direct TraY-DNA contacts. The third subsite
      appears to be oriented as an imperfect direct repeat with its adjacent subsite,
      although base substitutions at this subsite did not reduce binding. Although
      unusual for ribbon-helix-helix proteins, this binding site arrangement occurs at
      both F TraY sites, consistent with it being functionally relevant.

PMID- 12206774
TI  - Mutational analysis of the uracil DNA glycosylase inhibitor protein and its
      interaction with Escherichia coli uracil DNA glycosylase.
AB  - Uracil DNA glycosylase inhibitor (Ugi), a protein of 9.4 kDa consists of a five
      stranded antiparallel beta sheet flanked on either side by single alpha helices,
      forms an exclusive complex with uracil DNA glycosylases (UDGs) that is stable in
      8M urea. We report on the mutational analysis of various structural elements in
      Ugi, two of which (hydrophobic pocket and the beta1 edge) establish key
      interactions with Escherichia coli UDG. The point mutations in helix alpha1
      (amino acid residues 3-14) do not affect the stability of the UDG-Ugi complexes
      in urea. And, while the complex of the deltaN13 mutant with UDG is stable in only
      approximately 4M urea, its overall structure and thermostability are maintained.
      The identity of P37, stacked between P26 and W68, was not important for the
      maintenance of the hydrophobic pocket or for the stability of the complex.
      However, the M24K mutation at the rim of the hydrophobic pocket lowered the
      stability of the complex in 6M urea. On the other hand, non-conservative
      mutations E49G, D61G (cancels the only ionic interaction with UDG) and N76K, in
      three of the loops connecting the beta strands, conferred no such phenotype. The
      L23R and S21P mutations (beta1 edge) at the UDG-Ugi interface, and the N35D
      mutation far from the interface resulted in poor stability of the complex.
      However, the stability of the complexes was restored in the L23A, S21T and N35A
      mutations. These analyses and the studies on the exchange of Ugi mutants in
      preformed complexes with the substrate or the native Ugi have provided insights
      into the two-step mechanism of UDG-Ugi complex formation. Finally, we discuss the
      application of the Ugi isolates in overproduction of UDG mutants, toxic to cells.

PMID- 12206775
TI  - Zebularine: a novel DNA methylation inhibitor that forms a covalent complex with
      DNA methyltransferases.
AB  - Mechanism-based inhibitors of enzymes, which mimic reactive intermediates in the
      reaction pathway, have been deployed extensively in the analysis of metabolic
      pathways and as candidate drugs. The inhibition of cytosine-[C5]-specific DNA
      methyltransferases (C5 MTases) by oligodeoxynucleotides containing 5
      azadeoxycytidine (AzadC) and 5-fluorodeoxycytidine (FdC) provides a well
      documented example of mechanism-based inhibition of enzymes central to nucleic
      acid metabolism. Here, we describe the interaction between the C5 MTase from
      Haemophilus haemolyticus (M.HhaI) and an oligodeoxynucleotide duplex containing 2
      H pyrimidinone, an analogue often referred to as zebularine and known to give
      rise to high-affinity complexes with MTases. X-ray crystallography has
      demonstrated the formation of a covalent bond between M.HhaI and the 2-H
      pyrimidinone-containing oligodeoxynucleotide. This observation enables a
      comparison between the mechanisms of action of 2-H pyrimidinone with other
      mechanism-based inhibitors such as FdC. This novel complex provides a molecular
      explanation for the mechanism of action of the anti-cancer drug zebularine.

PMID- 12206777
TI  - ATP synthase from Saccharomyces cerevisiae: location of the OSCP subunit in the
      peripheral stalk region.
AB  - A biotinylation signal has been fused to the C terminus of the oligomycin
      sensitivity conferral protein (OSCP) of the ATP synthase complex from
      Saccharomyces cerevisiae. The signal is biotinylated in vivo and the biotinylated
      complex binds avidin in vitro. By electron microscopy of negatively stained
      particles of the ATP synthase-avidin complex, the bound avidin has been localised
      close to the F(1) domain. The images were subjected to multi-reference alignment
      and classification. Because of the presence of a flexible linker between the OSCP
      and the biotinylation signal, the class-averages differ in the position of the
      avidin relative to the F(1) domain. These positions lie on an arc, and its centre
      indicates the position of the C terminus of the OSCP on the surface of the F(1)
      domain. Since the N-terminal region of the OSCP is known to interact with the N
      terminal regions of alpha-subunits, which are on top of the F(1) domain distal
      from the F(o) membrane domain, the OSCP extends almost 10nm along the surface of
      F(1) down towards F(o) where it interacts with the C terminus of the b subunit,
      which extends up from F(o). The labelling technique has also allowed a reliable
      2D projection map to be developed for the intact ATP synthase from S.cerevisiae.
      The map reveals a marked asymmetry in the F(o) part of the complex that can be
      attributed to subunits in the F(o) domain.

PMID- 12206776
TI  - Enzyme-ligand complexes of pyridoxine 5'-phosphate synthase: implications for
      substrate binding and catalysis.
AB  - Pyridoxine 5'-phosphate (PNP) synthase is the last enzyme in the de novo
      biosynthesis of vitamin B(6) catalyzing the complicated ring-closure reaction
      between 1-deoxy-D-xylulose-5-phosphate and 1-amino-acetone-3-phosphate. Here we
      present the crystal structures of four PNP synthase complexes with substrates and
      substrate analogs. While the overall fold of the enzyme is conserved in all
      complexes, characteristic readjustments were observed in the active site. The
      complementary structural information allowed us to postulate a detailed reaction
      mechanism. The observed binding mode of substrates indicates how the first
      reaction intermediate, the Schiff-base conjugate, is formed. The most important
      mechanistic features are the presence of two phosphate-binding sites with
      distinct affinities and the existence of a water relay system for the release of
      reaction water molecules. Furthermore, the complexes provide the basis to
      rationalize the open-closed transition of a flexible loop located on the C
      terminal side of the TIM-barrel. Binding of both substrate molecules to the
      active site seems to be a prerequisite to trigger this transition. Highly
      conserved mechanistically important residues in the PNP synthase family imply a
      similar active site organization and reaction mechanism for all family members.
      Due to the exclusive presence of PNP synthase in a subset of eubacteria,
      including several well-known pathogens, and due to its outstanding physiological
      importance for these organisms, the enzyme appears to be a promising novel target
      for antibacterial drug design.

PMID- 12206779
TI  - Crystal structure of the jacalin-T-antigen complex and a comparative study of
      lectin-T-antigen complexes.
AB  - Thomsen-Friedenreich antigen (Galbeta1-3GalNAc), generally known as T-antigen, is
      expressed in more than 85% of human carcinomas. Therefore, proteins which
      specifically bind T-antigen have potential diagnostic value. Jacalin, a lectin
      from jack fruit (Artocarpus integrifolia) seeds, is a tetramer of molecular mass
      66kDa. It is one of the very few proteins which are known to bind T-antigen. The
      crystal structure of the jacalin-T-antigen complex has been determined at 1.62A
      resolution. The interactions of the disaccharide at the binding site are
      predominantly through the GalNAc moiety, with Gal interacting only through water
      molecules. They include a hydrogen bond between the anomeric oxygen of GalNAc and
      the pi electrons of an aromatic side-chain. Several intermolecular interactions
      involving the bound carbohydrate contribute to the stability of the crystal
      structure. The present structure, along with that of the Me-alpha-Gal complex,
      provides a reasonable qualitative explanation for the known affinities of jacalin
      to different carbohydrate ligands and a plausible model of the binding of the
      lectin to T-antigen O-linked to seryl or threonyl residues. Including the present
      one, the structures of five lectin-T-antigen complexes are available. GalNAc
      occupies the primary binding site in three of them, while Gal occupies the site
      in two. The choice appears to be related to the ability of the lectin to bind
      sialylated sugars. In either case, most of the lectin-disaccharide interactions
      are at the primary binding site. The conformation of T-antigen in the five
      complexes is nearly the same.

PMID- 12206778
TI  - Crystal structures of the reaction intermediate and its homologue of an extradiol
      cleaving catecholic dioxygenase.
AB  - BphC derived from Pseudomonas sp. strain KKS102 is an extradiol-cleaving
      catecholic dioxygenase. This enzyme contains a non-heme iron atom and plays an
      important role in degrading biphenyl/polychlorinated biphenyls (PCBs) in the
      microbe. To elucidate detailed structures of BphC reaction intermediates, crystal
      structures of the substrate-free form, the BphC-substrate complex, and the BphC
      substrate-NO (nitric oxide) complex were determined. These crystal structures
      revealed (1) the binding site of the O(2) molecule in the coordination sphere and
      (2) conformational changes of His194 during the catalytic reaction. On the basis
      of these findings, we propose a catalytic mechanism for the extradiol-cleaving
      catecholic dioxygenase in which His194 seems to play three distinct roles. At the
      early stage of the catalytic reaction, His194 appears to act as a catalytic base,
      which likely deprotonates the hydroxyl group of the substrate. At the next stage,
      the protonated His194 seems to stabilize a negative charge on the O2 molecule
      located in the hydrophobic O2-binding cavity. Finally, protonated His194 seems to
      function as a proton donor, whose existence has been proposed.

PMID- 12206780
TI  - NMR structures of two variants of bovine pancreatic trypsin inhibitor (BPTI)
      reveal unexpected influence of mutations on protein structure and stability.
AB  - Here we determined NMR solution structures of two mutants of bovine pancreatic
      trypsin inhibitor (BPTI) to reveal structural reasons of their decreased
      thermodynamic stability. A point mutation, A16V, in the solvent-exposed loop
      destabilizes the protein by 20 degrees C, in contrast to marginal destabilization
      observed for G, S, R, L or W mutants. In the second mutant introduction of eight
      alanine residues at proteinase-contacting sites (residues 11, 13, 17, 18, 19, 34,
      37 and 39) provides a protein that denatures at a temperature about 30 degrees C
      higher than expected from additive behavior of individual mutations. In order to
      efficiently determine structures of these variants, we applied a procedure that
      allows us to share data between regions unaffected by mutation(s). NOAH/DYANA and
      CNS programs were used for a rapid assignment of NOESY cross-peaks, structure
      calculations and refinement. The solution structure of the A16V mutant reveals no
      conformational change within the molecule, but shows close contacts between V16,
      I18 and G36/G37. Thus, the observed 4.3kcal/mol decrease of stability results
      from a strained local conformation of these residues caused by introduction of a
      beta-branched Val side-chain. Contrary to the A16V mutation, introduction of
      eight alanine residues produces significant conformational changes, manifested in
      over a 9A shift of the Y35 side-chain. This structural rearrangement provides
      about 6kcal/mol non-additive stabilization energy, compared to the mutant in
      which G37 and R39 are not mutated to alanine residues.

PMID- 12206781
TI  - Dynamics of hydrogen bond desolvation in protein folding.
AB  - As proteins fold, a progressive structuring, immobilization and eventual
      exclusion of water surrounding backbone hydrogen bonds takes place. This process
      turns hydrogen bonds into major determinants of the folding pathway and
      compensates for the penalty of desolvation of the backbone polar groups. Taken as
      an average over all hydrogen bonds in a native fold, this extent of protection is
      found to be nearly ubiquitous. It is dynamically crucial, determining a
      constraint in the long-time limit behavior of coarse-grained ab initio
      simulations. Furthermore, an examination of one of the longest available
      (1micros) all-atom simulations with explicit solvent reveals that this average
      extent of protection is a constant of motion for the folding trajectory. We
      propose how such a stabilization is best achieved by clustering five hydrophobes
      around the backbone hydrogen bonds, an arrangement that yields the optimal
      stabilization. Our results support and clarify the view that hydrophobic surface
      burial should be commensurate with hydrogen-bond formation and enable us to
      define a basic desolvation motif inherent to structure and folding dynamics.

PMID- 12206782
TI  - Structure-based combinatorial protein engineering (SCOPE).
AB  - Presented here is the development a semi-rational protein engineering approach
      that uses information from protein structure coupled with established DNA
      manipulation techniques to design and create multiple crossover libraries from
      non-homologous genes. The utility of structure-based combinatorial protein
      engineering (SCOPE) was demonstrated by its application to two distantly related
      members of the X-family of DNA polymerases: rat DNA polymerase beta (Pol beta)
      and African swine fever virus DNA polymerase X (Pol X). These proteins share
      similar folds but have low sequence identity, and differ greatly in both size and
      activity. "Equivalent" subdomain elements of structure were designed on the basis
      of the tertiary structure of Pol beta and the corresponding regions of Pol X were
      inferred from homology modeling and sequence alignment analysis. Libraries of
      chimeric genes with up to five crossovers were synthesized in a series of PCR
      reactions by employing hybrid oligonucleotides that code for variable connections
      between structural elements. Genetic complementation in Escherichia coli enabled
      identification of several novel DNA polymerases with enhanced phenotypes. Both
      the composition of structural elements and the manner in which they were linked
      were shown to be essential for this property, indicating the importance of these
      aspects of design.

PMID- 12206783
TI  - The unfolding of oxidized c-type cytochromes: the instructive case of Bacillus
      pasteurii.
AB  - The reversible unfolding of oxidized Bacillus pasteurii cytochrome c(553) by
      guanidinium chloride under equilibrium conditions has been monitored by NMR and
      optical spectroscopy. The results obtained indicate that unfolding takes place
      through a mechanism involving the detachment from heme iron coordination of the
      sulfur of the Met71 axial ligand and yielding either a high spin (HS) or a low
      spin (LS(1)) species, depending on the pH value. In the LS(1) form the Met71 is
      replaced by another protein ligand, possibly Lys. The ligand exchange reaction
      does not reach completion until the protein backbone reaches a largely unfolded
      state, as monitored through 1H-15N NMR experiments, thus demonstrating that there
      is a significant correlation between formation of the Fe-S bond and native
      structure stability. 1H/2H exchange data, however, show that helix alpha(3), the
      C-terminal region of helix alpha(4), and helix alpha(5) maintain low
      exchangeability of the amide protons in the LS(1) form. This finding most likely
      implies that these regions maintain some ordered non-covalent structure, in which
      the amide moieties are involved in H-bonds. Finally, a folding mechanism is
      proposed and discussed in terms of analogies and differences with the larger
      mitochondrial cytochrome c proteins. It is concluded that the thermodynamic
      stability of the region around the metal cofactor is determined by the chemical
      nature of the residues around the axial methionine residue.

PMID- 12206784
TI  - Domain organization of D-AKAP2 revealed by enhanced deuterium exchange-mass
      spectrometry (DXMS).
AB  - Dual specific A-kinase anchoring protein 2 (D-AKAP2) is a scaffold protein that
      coordinates cAMP-mediated signaling complexes by binding to type I and type II
      protein kinase A (PKA). While information is unfolding regarding specific binding
      motifs, very little is known about the overall structure and dynamics of these
      scaffold proteins. We have used deuterium exchange-mass spectrometry (DXMS) and
      limited proteolysis to probe the folded regions of D-AKAP2, providing for the
      first time insight into the intra-domain dynamics of a scaffold protein.
      Deuterium on-exchange revealed two regions of low deuterium exchange that were
      surrounded by regions of high exchange, suggestive of two distinctly folded
      regions, flanked by disordered or solvent accessible regions. Similar folded
      regions were detected by limited proteolysis. The first folded region contained a
      putative regulator of G-protein signaling (RGS) domain. A structural model of the
      RGS domain revealed that the more deuterated regions mapped onto loops and turns,
      whereas less deuterated regions mapped onto alpha-helices, consistent with this
      region folding into an RGS domain. The second folded region contained a highly
      protected PKA binding site and a more solvent-accessible PDZ binding motif, which
      may serve as a potential targeting domain for D-AKAP2. DXMS has verified the
      multi-domain architecture of D-AKAP2 implied by sequence homology and has
      provided unique insight into the accessibility of the PKA binding site.

PMID- 12206785
TI  - Crystallographic structure of the K intermediate of bacteriorhodopsin:
      conservation of free energy after photoisomerization of the retinal.
AB  - The K state, an early intermediate of the bacteriorhodopsin photocycle, contains
      the excess free energy used for light-driven proton transport. The energy gain
      must reside in or near the photoisomerized retinal, but in what form has long
      been an open question. We produced the K intermediate in bacteriorhodopsin
      crystals in a photostationary state at 100K, with 40% yield, and determined its X
      ray diffraction structure to 1.43 A resolution. In independent refinements of
      data from four crystals, the changes are confined mainly to the photoisomerized
      retinal. The retinal is 13-cis,15-anti, as known from vibrational spectroscopy.
      The C13=C14 bond is rotated nearly fully to cis from the initial trans
      configuration, but the C14-C15 and C15=NZ bonds are partially counter-rotated.
      This strained geometry keeps the direction of the Schiff base N-H bond vector
      roughly in the extracellular direction, but the angle of its hydrogen bond with
      water 402, that connects it to the anionic Asp85 and Asp212, is not optimal.
      Weakening of this hydrogen bond may account for many of the reported features of
      the infrared spectrum of K, and for its photoelectric signal, as well as the
      deprotonation of the Schiff base later in the cycle. Importantly, although 13
      cis, the retinal does not assume the expected bent shape of this configuration.
      Comparison of the calculated energy of the increased angle of C12-C13=C14, that
      allows this distortion, with the earlier reported calorimetric measurement of the
      enthalpy gain of the K state indicates that a significant part of the excess
      energy is conserved in the bond strain at C13.

PMID- 12206787
TI  - Therapeutic possibilities in Duchenne muscular dystrophy. Proceedings of the
      special centennial international ENMC workshop. Naarden, The Netherlands, 30
      November-2 December 2001.

PMID- 12206786
TI  - Crystallographic structure of the retinal and the protein after deprotonation of
      the Schiff base: the switch in the bacteriorhodopsin photocycle.
AB  - We illuminated bacteriorhodopsin crystals at 210K to produce, in a
      photostationary state with 60% occupancy, the earliest M intermediate (M1) of the
      photocycle. The crystal structure of this state was then determined from X-ray
      diffraction to 1.43 A resolution. When the refined model is placed after the
      recently determined structure for the K intermediate but before the reported
      structures for two later M states, a sequence of structural changes becomes
      evident in which movements of protein atoms and bound water are coordinated with
      relaxation of the initially strained photoisomerized 13-cis,15-anti retinal. In
      the K state only retinal atoms are displaced, but in M1 water 402 moves also,
      nearly 1A away from the unprotonated retinal Schiff base nitrogen. This breaks
      the hydrogen bond that bridges them, and initiates rearrangements of the hydrogen
      bonded network of the extracellular region that develop more fully in the
      intermediates that follow. In the M1 to M2 transition, relaxation of the C14-C15
      and C15=NZ torsion angles to near 180 degrees reorients the retinylidene nitrogen
      atom from the extracellular to the cytoplasmic direction, water 402 becomes
      undetectable, and the side-chain of Arg82 is displaced strongly toward Glu194 and
      Glu204. Finally, in the M2 to M2' transition, correlated with release of a proton
      to the extracellular surface, the retinal assumes a virtually fully relaxed bent
      shape, and the 13-methyl group thrusts against the indole ring of Trp182 which
      tilts in the cytoplasmic direction. Comparison of the structures of M1 and M2
      reveals the principal switch in the photocycle: the change of the angle of the
      C15=NZ-CE plane breaks the connection of the unprotonated Schiff base to the
      extracellular side and establishes its connection to the cytoplasmic side.

PMID- 12206788
TI  - Myoblast transplantation.
AB  - Myoblast transplantation was the first quasi-gene therapy to be suggested for
      Duchenne muscular dystrophy. Animal experiments established the principles that
      the missing gene could be targeted to muscle by grafting of genetically normal
      myoblasts that were able to repair the disease-damaged muscle fibres. In the
      recipient muscle the gene was expressed and the resultant protein provided some
      functional benefit in protecting the fibres against necrosis. However, these
      effects were limited to a small region around the injection site and there was
      some evidence of immunological problems. Human trials provided little evidence of
      effectiveness probably, in part due to immune rejection, and in part to the
      inadequacy of the cells implanted. Most work since this time has been directed at
      preventing immune rejection, improving dispersion of the injected cells, and
      selecting more 'stem cell-like' myogenic cells which might be more effective at
      reconstituting large regions of muscle. Most recently, a number of sources of
      'stem cell' with myogenic potential have been described, some of which have been
      found to be dispersed via the blood vascular system but none of which have been
      very efficient at generating new muscle.

PMID- 12206789
TI  - Myogenic stem cells from the bone marrow: a therapeutic alternative for muscular
      dystrophy?
AB  - Differentiated muscle fibres can be formed by transplanted haematopoietic stem
      cells in models of acute or chronic muscle regeneration, including the dystrophin
      deficient mdx mouse. Muscle-forming activity can be found in adult, foetal and
      embryonic haematopoietic tissues. The blood-to-muscle transition may be due to
      transdifferentiation of haematopoietic progenitors in response to local signals
      provided by the regenerating muscle. These signals are only poorly provided by
      the muscle of the mdx mouse, since transplantation into these mice of normal
      C57Bl/6 bone marrow gives rise only to a minimal number of muscle fibres
      expressing the normal dystrophin protein (<1%) throughout the animal life span.
      Expansion and active recruitment to myogenic differentiation of transplanted
      haematopoietic cells are therefore critical factors for a future use of bone
      marrow transplantation in cell/gene therapy of muscular dystrophy.

PMID- 12206790
TI  - Gene transfer studies in animals: what do they really tell us about the prospects
      for gene therapy in DMD?
AB  - There is a pressing need to develop new therapeutic approaches to Duchenne
      muscular dystrophy, an X-linked fatal disease primarily affecting skeletal and
      cardiac muscle. Gene therapy is an approach that has attracted much interest
      since the description of the Duchenne muscular dystrophy gene and its mutations
      in 1987. Since 1990 numerous reporter and dystrophin gene transfer studies have
      been conducted on muscles of animals but mostly in mice. Experimental protocols
      have ranged from germ-line gene transfer (via the production of transgenics) to
      somatic gene transfer studies using viral or non-viral vectors. But what have we
      actually learned from such studies that can be applied to patients with Duchenne
      muscular dystrophy? Various dystrophin, utrophin and integrin recombinant cDNAs
      have been shown to prevent the development of muscular dystrophy in transgenic
      dystrophic (mdx) mice. Somatic gene transfer prior to the onset of pathology have
      been shown to prevent the development of the muscular dystrophy in the mdx mouse
      but the data is less convincing for the beneficial effects of somatic gene
      transfer following the establishment of pathology. The time of onset and the
      course of the disease differ substantially between mouse and man and raise
      concerns about the applicability of gene therapy in man where the disease
      manifests in utero and the progression is more severe. The other major concern
      relates to uncertainty over the efficiency of the different vectors in man,
      particularly as many patients are likely to have encountered the infectious forms
      of the viruses that are proposed as vectors.

PMID- 12206791
TI  - Viral vectors for gene transfer of micro-, mini-, or full-length dystrophin.
AB  - Gene therapy for Duchenne muscular dystrophy will require methods to deliver gene
      constructs encoding functional versions of dystrophin to the vast majority of a
      patient's musculature. Obstacles to achieving these goals include identifying
      which forms of dystrophin would be effective in a clinical setting and developing
      gene delivery shuttles capable of carrying and expressing dystrophin cassettes
      without toxic or adverse immunologic consequences. We review here recent work
      from our laboratory to identify sequences within dystrophin that are required to
      prevent development of dystrophic changes in muscle or which might be able to
      correct pre-existing damage. We also describe work aimed at developing viral
      shuttle vectors able to carry and express these dystrophin cassettes at high
      levels and in a muscle-specific fashion. While great challenges remain in
      developing methods for systemic gene delivery, we show that a variety of viral
      vectors are able to carry and express therapeutic levels of dystrophin when
      delivered directly to mouse skeletal muscle.

PMID- 12206792
TI  - Strategies for muscle-specific targeting of adenoviral gene transfer vectors.
AB  - Currently, adenoviral transfer of therapeutic genes such as dystrophin is
      hampered by low transduction efficiency of adult skeletal muscle. This is largely
      due to the lack of appropriate virus attachment receptors on the myofiber
      surface. Recent studies in transgenic mice revealed that upregulation of
      Coxsackie- and adenovirus receptor improves gene transfer efficiency by
      approximately ten-fold. Conversely, the vector load that needed to be
      administered to achieve sufficient gene transfer could be lowered significantly.
      Reduced viral vector loads may help to control virally mediated toxicity and
      immunogenicity. To date, there are no drugs or methods known to increase
      Coxsackie- and adenovirus receptor expression in skeletal muscle that would be
      easily applicable in humans. However, alternative strategies such as vector
      retargeting are currently being investigated that may allow for an increase in
      binding of adenoviral vectors to skeletal muscle. Recent experiments have shown
      that directed mutagenesis of the adenoviral fiber knob allows for a significant
      reduction in Coxsackie- and adenovirus receptor binding and for introduction of a
      new binding domain. Therefore, vector retargeting towards efficient and specific
      infection of skeletal muscle may be achieved by directed genetic alteration of
      adenoviral capsid proteins.

PMID- 12206793
TI  - Recombinant micro-genes and dystrophin viral vectors.
AB  - An effective gene therapy for Duchenne muscular dystrophy ideally relies on the
      ability to provide long-term expression to muscle tissue of the missing protein,
      dystrophin. Early work in the mdx mouse using a 6.3 kb mini-dystrophin cDNA,
      carried out in either adenoviral or retroviral vectors was generally successful,
      however, expression was only transient. In an attempt to remedy this problem, two
      approaches are being investigated. The first of these is a hybrid vector system
      that combines the efficacy of gene transfer into skeletal muscle of adenoviral
      vectors with the long-term stability of retroviral vectors. The second utilises
      the inherently efficient transducing properties and stability of the adeno
      associated viral delivery system. Using highly truncated micro-dystrophin cDNAs
      we have shown that both vector systems were able to restore dystrophin and
      dystrophin-associated protein expression at the plasma membrane of mdx mice for
      prolonged periods of time. Additionally, evaluation of central nucleation
      indicated a significant inhibition of degenerative dystrophic muscle pathology.
      These studies suggest that hybrid adenoviral-retroviral and adeno-associated
      viral vectors are capable of ameliorating dystrophic pathology at the cellular
      level and as such are useful tools in the development of a gene therapy for
      Duchenne muscular dystrophy.

PMID- 12206794
TI  - Current protocol of a research phase I clinical trial of full-length dystrophin
      plasmid DNA in Duchenne/Becker muscular dystrophies. Part II: clinical protocol.
AB  - A phase I open clinical study on gene therapy in Duchenne and Becker muscular
      dystrophy, without direct individual benefit for the patient, is being performed
      at the Pitie-Salpetriere Hospital, Paris. The aims of this project are: (a) to
      determine the tolerance and the safety of the intramuscular administration of
      dystrophin cDNA and (b) to study the quality of the gene transfer in vivo in
      human patients affected by Duchenne and Becker muscular dystrophy. This clinical
      trial is conducted sequentially and includes three cohorts of three patients
      each. Patients must be at least 15 years of age. Diagnosis of Duchenne and Becker
      muscular dystrophy was confirmed by molecular analysis of the dystrophin gene and
      for each patient the abnormal expression of dystrophin was confirmed, in skeletal
      muscle, with antibodies directed against the deleted part of the dystrophin. This
      phase I study is scheduled to be completed by the end of 2002.

PMID- 12206796
TI  - Current protocol of a research phase I clinical trial of full-length dystrophin
      plasmid DNA in Duchenne/Becker muscular dystrophies. Part III. Ethical
      considerations.
AB  - Ethical aspects on human gene therapy are briefly discussed, in relation to the
      protocol developed in Duchenne/Becker muscular dystrophy with a full-length
      dystrophin plasmid. Differences between somatic therapies--as considered in this
      study--and germline gene interventions are underlined. Regulatory aspects for
      France are summarized. Special emphasis is put on the necessary control of
      publicity in the lay media in such a clinical study.

PMID- 12206795
TI  - Current protocol of a research phase I clinical trial of full-length dystrophin
      plasmid DNA in Duchenne/Becker muscular dystrophies. Part I: rationale.
AB  - Since the identification of abnormalities in the dystrophin gene as primary cause
      of Duchenne muscular dystrophy, gene therapy has been seen as an obvious option
      among various approaches to treat the disease. It is also considered to be
      especially challenging, as in this context, one must achieve massive transfer of
      the gene with a sustained lifelong correction of the muscle phenotype. Our goal
      is to allow large scale transfection of skeletal muscle fibers of Duchenne
      muscular dystrophy patients with the full-length 11-kb human dystrophin cDNA.
      Extensive in vitro and in vivo studies, together with safety considerations and
      the prospects of a very efficient intra-arterial delivery procedure, led us
      progressively to focus our efforts on plasmid DNA administration. We are now
      conducting a phase I safety clinical trial which will pave the way for future
      therapeutic gene therapy trials for Duchenne muscular dystrophy.

PMID- 12206797
TI  - Oligonucleotide-mediated gene therapy for muscular dystrophies.
AB  - Several new approaches to gene therapy for the muscular dystrophies involve
      oligonucleotides as targeting vectors. These oligonucleotides are designed to
      repair genetic mutations, to modify genomic sequences in order to compensate for
      gene deletions, or to modify RNA processing in order to ameliorate the effects of
      the underlying gene mutation. Among the various approaches currently under
      investigation for dystrophin mutations that cause Duchenne muscular dystrophy is
      the use of chimeric RNA/DNA oligonucleotides ("chimeraplasts") to repair point
      mutations. Studies in the mdx mouse and the GRMD dog have demonstrated that point
      mutations in the dystrophin gene can be corrected by chimeraplasts that have been
      injected into muscles. The scope of this review includes a summary of the current
      status of chimeraplast-mediated gene repair for dystrophin mutations, ongoing
      studies to apply chimeraplast-mediated gene repair to frame-shift deletions of
      the dystrophin gene, and major hurdles that need to be overcome to translate
      current experimental successes into a viable therapeutic modality for Duchenne
      muscular dystrophy.

PMID- 12206798
TI  - CD45 fraction bone marrow cells as potential delivery vehicles for genetically
      corrected dystrophin loci.
AB  - Targeted correction of mutations in muscle can be delivered by direct i.m.
      injection of corrective DNA to the dystrophic muscle or by autologous injection
      of cells that have been genetically corrected after isolation from the individual
      with the dystrophic muscle. The successful application of chimeraplasty and short
      fragment homologous replacement to correct the exon 23 nonsense mdx transition at
      the mouse dys locus has opened up the possibility that with further development,
      targeted gene correction may have some future application for the treatment of
      muscular dystrophies. In vitro, application of targeted gene correction at the
      mdx dys locus results in better correction efficiencies than when applied
      directly to dystrophic muscle. This suggests that at least for the time being, a
      strategy involving ex vivo correction may be advantageous over a direct approach
      for delivery of gene correction to dystrophic muscle. This, particularly in view
      of recent developments indicating that bone-marrow-derived cells are able to
      systemically remodel dystrophic muscle, whilst penetration of DNA introduced to
      muscle is limited to individually injected muscles. Application of targeted gene
      correction to Duchenne dystrophy needs to account for the fact that about 65% of
      Duchenne muscular dystrophy cases involve large frame-shift deletion of gene
      sequence at the dys locus. Traditionally, whilst targeted gene correction is able
      to restore point mutations entirely, it remains to be seen as to whether a
      strategy for the 'correction' of frame shift deletions may be engineered
      successfully. This communication discusses the possibility of applying targeted
      gene correction to dystrophic muscle in Duchenne dystrophy.

PMID- 12206799
TI  - Screening for antisense modulation of dystrophin pre-mRNA splicing.
AB  - Most gene therapy approaches to genetic disorders aim to compensate loss-of
      function by introducing recombinant cDNA-based minigenes into diseased tissues.
      The current report represents an ongoing series of studies designed to correct
      genetic mutations at the post-transcriptional level. This strategy modifies the
      binding of components of the spliceosome by high affinity hybridisation of small
      complementary (antisense) RNA oligonucleotides to specific pre-mRNA sequences.
      These, so-called 'splicomer' reagents are chemically modified to impart bio
      stability, and are designed to cause skipping of mutant frame-shifting exon
      sequences leading to restoration of the reading frame and an internally deleted
      but partially functional gene product. For instance, Duchenne muscular dystrophy
      is generally caused by frame-shift mutations in the dystrophin gene, whereas in
      frame deletions of up to 50% of the central portion of the gene cause Becker
      muscular dystrophy, a much milder myopathy, which in some cases can remain
      asymptomatic to old age. In the mdx mouse model of Duchenne muscular dystrophy, a
      mutation in exon 23 of the dystrophin gene creates a stop codon and leads to a
      dystrophin-deficient myopathy in striated muscle. In previous studies, we have
      demonstrated that forced skipping of this mutant exon by treatment of mdx muscle
      cells with splicomer oligonucleotides can generate in-frame dystrophin
      transcripts and restore dystrophin expression. Here, we report the results of an
      optimisation of splicomer sequence design by the use of both high-throughput
      arrays and biological screens. This has resulted in specific and, importantly,
      exclusive skipping of the targeted exon in greater than 60% of dystrophin mRNA,
      leading to the de novo synthesis and localisation of dystrophin protein in
      cultured mdx muscle cells.

PMID- 12206800
TI  - Targeted exon skipping as a potential gene correction therapy for Duchenne
      muscular dystrophy.
AB  - Duchenne muscular dystrophy is primarily caused by frame-disrupting mutations in
      the Duchenne muscular dystrophy gene which abort dystrophin synthesis. We have
      explored a gene correction therapy aimed at restoration of the reading frame in
      Duchenne muscular dystrophy patients. Through the binding of antisense
      oligoribonucleotides to exon-internal sequences in the pre-mRNA, the splicing can
      be manipulated in such a manner that the targeted exon is skipped and a slightly
      shorter, but in-frame, transcript is generated. We recently showed that antisense
      oligoribonucleotide-mediated skipping of exon 46 efficiently induced dystrophin
      synthesis in cultured muscle cells from Duchenne muscular dystrophy patients
      carrying an exon 45 deletion. In this study we have identified antisense
      oligoribonucleotides with which the skipping of 11 other Duchenne muscular
      dystrophy exons could be induced in cultured human muscle cells. The targeted
      skipping of only one particular exon may restore the reading frame in a series of
      patients with different mutations. Accordingly, these antisense
      oligoribonucleotides would allow correction of over 50% of deletions and 22% of
      duplications reported in the Leiden DMD-mutation Database.

PMID- 12206801
TI  - The role of utrophin in the potential therapy of Duchenne muscular dystrophy.
AB  - Duchenne muscular dystrophy is an X-linked recessive muscle wasting disease
      caused by the absence of the muscle cytoskeletal protein, dystrophin. Dystrophin
      is a member of the spectrin superfamily of proteins and is closely related in
      sequence similarity and functional motifs to three proteins that constitute the
      dystrophin related protein family, including the autosomal homologue, utrophin.
      An alternative strategy circumventing many problems associated with somatic gene
      therapies for Duchenne muscular dystrophy has arisen from the demonstration that
      utrophin can functionally substitute for dystrophin and its over-expression in
      muscles of dystrophin-null transgenic mice completely prevents the phenotype
      arising from dystrophin deficiency. One potential approach to increase utrophin
      levels in muscle for possible therapeutic purpose in humans is to increase
      expression of the utrophin gene at a transcriptional level via promoter
      activation. This has lead to an interest in the identification and manipulation
      of important regulatory regions and/or molecules that increase the expression of
      utrophin and their delivery to dystrophin-deficient tissue. As pre-existing
      cellular mechanisms are utilized, this approach would avoid many problems
      associated with conventional gene therapies.

PMID- 12206802
TI  - Multivariate evaluation of the functional recovery obtained by the overexpression
      of utrophin in skeletal muscles of the mdx mouse.
AB  - This paper summarizes the various aspects of functional recovery obtained in
      dystrophin-deficient muscles of the mdx mice where utrophin was overexpressed.
      This includes preliminary results on tetracycline-controlled expression of
      utrophin. It is shown that overexpression of utrophin leads to major functional
      improvements and that full-length utrophin is more efficient than truncated
      utrophin, missing a part of the central rod-segment. A generalized way of
      presenting improvements obtained by any treatment in the form of a 'recovery
      score' is emphasized. The quantitative aspect of the replacement of dystrophin by
      utrophin is discussed.

PMID- 12206803
TI  - Glucocorticoid-mediated regulation of utrophin levels in human muscle fibers.
AB  - Previous studies on transgenic mice indicate that upregulation of utrophin
      protein may offer a potential treatment strategy for Duchenne muscular dystrophy.
      We have analyzed the effect of the glucocorticoid 6alpha-methylprednisolone-21
      sodium succinate on utrophin protein levels, using a cell-based assay with
      differentiated human myotubes, derived from biopsies of healthy individuals or
      Duchenne muscular dystrophy patients. We found that within 5-7 days 6alpha
      methylprednisolone-21 sodium succinate increases utrophin protein up to
      approximately 40% in both normal and dystrophin-deficient myotubes compared to
      untreated control cultures. When analyzed in promoter-reporter assays 6alpha
      methylprednisolone-21 sodium succinate activated a utrophin promoter A-fragment
      but did not activate a utrophin promoter B-fragment. Surprisingly, endogenous
      levels of utrophin mRNA in 6alpha-methylprednisolone-21 sodium succinate-treated
      muscle cells were unaltered indicating that the utrophin-inducing effect of
      glucocorticoids may be a result of post-transcriptional mechanisms. We have also
      analyzed 66 glucocorticoids for their effect on utrophin protein levels and found
      that glucocorticoids in general are able to induce utrophin protein in human
      myotubes.

PMID- 12206804
TI  - Dystrophin and functionally related proteins in the nematode Caenorhabditis
      elegans.
AB  - We investigated the function of dystrophin in the nematode Caenorhabditis
      elegans. Although nematodes and mammals diverged early in evolution, their
      muscles share many structural and molecular features, thus rendering C. elegans
      relevant as a model to study muscle function. Dystrophin, dystrobrevin,
      dystroglycans and several sarcoglycans have conserved homologues in the genome of
      C. elegans. The major strength of the model comes from its genetic tractability,
      which allows the quick and easy manipulation of gene expression, either to
      inactivate genes, or to create transgenic animals. Over the last 2 years, work on
      C. elegans dystrophin has led to the identification of a putative new member of
      the dystrophin-glycoprotein complex, and has brought additional data suggesting
      that dystrophin mutations affect ion channel function.

PMID- 12206805
TI  - Dystrobrevin dynamics in muscle-cell signalling: a possible target for
      therapeutic intervention in Duchenne muscular dystrophy?
AB  - The dystrophin-protein complex forms one of the connections between the
      extracellular matrix and the cytoskeleton of muscle. This link is disrupted in
      patients with Duchenne and Becker muscular dystrophies. Dystrobrevin is a
      component of the dystrophin-protein complex that binds to the C-terminus of
      dystrophin and also to syntrophin. As its name suggests, dystrobrevin is a
      relative of dystrophin participating in similar intermolecular interactions.
      Dystrobrevin-deficient mice have a form of muscular dystrophy that leaves the
      sarcolemma and dystrophin-protein complex intact but affects an as yet
      unidentified signalling pathway in muscle. Given that the up-regulation of
      several genes has a beneficial effect on the muscle in some dystrophic mouse
      models, alpha-dystrobrevin has a number of properties that might be protective in
      muscular dystrophy. This article discusses the function of dystrobrevin in muscle
      and reviews its suitability as a therapeutic target for treating patients with
      Duchenne and Becker muscular dystrophies.

PMID- 12206806
TI  - Expression profiling in stably regenerating skeletal muscle of dystrophin
      deficient mdx mice.
AB  - The mdx mouse is comparable to Duchenne muscular dystrophy in having an absence
      of dystrophin. While dystrophic human skeletal muscle undergoes progressive
      degeneration, in the mdx mouse regeneration and tissue remodeling substantially
      compensate for the lack of dystrophin. To better understand the molecular events
      leading to active muscle regeneration in mdx muscles, we have determined the gene
      expression profiles of wild-type and mdx hind limb muscles using oligonucleotide
      arrays. Compared to wild-type, 58 genes were found to be differentially expressed
      in mdx. The molecular signature of actively regenerating skeletal muscle in young
      adult mdx mice showed upregulation of muscle development genes and genes involved
      in immune response, proteolysis and extracellular matrix remodeling. Moreover,
      energy metabolism and mitochondrial function were not compromised. Insights into
      the processes activated in the mdx muscle to compensate for chronic degeneration
      may have important implications for therapy in patients with muscular dystrophy.

PMID- 12206807
TI  - A web-accessible complete transcriptome of normal human and DMD muscle.
AB  - We present an assessment of the complete transcriptome of human skeletal muscle
      in Duchenne muscular dystrophy patient muscle and non-dystrophic controls (36
      RNAs analyzed from ten Duchenne dystrophy and eight controls; approximately
      65,000 gene/expressed sequence tag/probe sets queried on U95 five-GeneChip series
      and MuscleChip). The use of the multiple chip types allowed us to compare results
      from different probe sets for the same gene: we found excellent concordance
      between different probe sets on different microarrays. We found 30% of human
      genes expressed in muscle at detectable levels. Three percent of these showed
      differential regulation in dystrophin deficiency. Among 1,882 dysregulated probe
      sets, 1,324 corresponded to characterized genes/proteins (891 non-redundant
      transcript units), and 588 to expressed sequence tags or predicted genes. Data
      interpretation was limited to the insulin-like growth factor pathway members, an
      investigation of possible de-regulation towards a cardiac lineage, and
      identification of male- and female-specific transcripts. We found transcriptional
      upregulation of both IGF-I and IGF-II in dystrophic muscle, however the possible
      beneficial effects of the growth factors appear offset by transcriptional
      upregulation of inhibitory IGF-binding proteins and regulators (IGFBP-2, -4, -6
      and -7; and PRSS11 [IGFBP-5 protease]). We hypothesize that the beneficial
      effects of IGF-I or IGF-II supplementation in dystrophic muscle may be the result
      of dose-dependent sequestration of inhibitory IGF-binding proteins. We also
      focused on six 'cardiac' genes expressed in muscle (alpha-cardiac actin, CARP,
      CASQ2, troponin T2 cardiac [TNNT2], CUGBP2, and connexin 43). Comparison to a 27
      time point murine muscle regeneration series and mdx muscle profiles showed that
      CARP and Cx43 were macrophage-associated, and TNNT2 activated-myoblast
      associated. Upregulation of cardiac actin and CUGBP2 was not associated with
      muscle regeneration profiles, suggesting a more specific dysregulation induced by
      dystrophin deficiency. We found two Y-linked genes expressed solely in male
      muscle (RPS4Y, DDX3Y), and two autosomal genes expressed much more highly in
      female muscle (GRO2, ZNF91) (all comparisons P<0.01). Finally, we present the
      first web-accessible expression profiling database for all data, including image
      files (.dat), processed image files (.cel), and complete comparison files which
      are publicly available through a novel queriable web site, that permits query-by
      gene across all profiles (http://microarray.cnmcresearch.org/pga). These data
      enumerate the full range of molecular changes associated downstream of dystrophin
      deficiency, and provide a web-accessible platform to study the specificity of
      transcriptional pathway alterations in muscle disease.

PMID- 12206808
TI  - Pre-clinical trials in Duchenne dystrophy: what animal models can tell us about
      potential drug effectiveness.
AB  - The symptomatic pharmacological therapy of Duchenne dystrophy is poor,
      glucocorticoids being the sole compounds showing a certain efficacy, although
      their use is restricted by serious side effects. Pre-clinical trials of prompt-to
      use drugs need reliable animal models of the human disease to predict drug
      effectiveness in patients. The exercised mdx mouse develops a typical pattern of
      muscle weakness in vivo, which has already been used as an index on which to
      evaluate drug effectiveness. We have demonstrated that the macroscopic
      conductance to chloride ion, an index of degeneration-regeneration events
      occurring in mdx mouse muscles, is specifically impaired by a chronic exercise
      protocol and is sensitive to the action of in vivo administered drugs acting
      either by stimulating regeneration (insulin-like growth factor-1 and steroids) or
      by counteracting calcium-induced degeneration or inflammation (Taurine and
      steroids). The monitoring of conductance to chloride ion also allows the
      evaluation of false positive compounds, effective on mouse strength in vivo but
      not at muscle level, and the functional correlation with other cellular
      parameters.

PMID- 12206809
TI  - Collaborative translational research leading to multicenter clinical trials in
      Duchenne muscular dystrophy: the Cooperative International Neuromuscular Research
      Group (CINRG).
AB  - Progress in the development of rationally based therapies for Duchenne muscular
      dystrophy has been accelerated by encouraging multidisciplinary, multi
      institutional collaboration between basic science and clinical investigators in
      the Cooperative International Research Group. We combined existing research
      efforts in pathophysiology by a gene expression profiling laboratory with the
      efforts of animal facilities capable of conducting high-throughput drug screening
      and toxicity testing to identify safe and effective drug compounds that target
      different parts of the pathophysiologic cascade in a genome-wide drug discovery
      approach. Simultaneously, we developed a clinical trial coordinating center and
      an international network of collaborating physicians and clinics where those
      drugs could be tested in large-scale clinical trials. We hope that by bringing
      together investigators at these facilities and providing the infrastructure to
      support their research, we can rapidly move new bench discoveries through animal
      model screening and into therapeutic testing in humans in a safe, timely and cost
      effective setting.

PMID- 12206810
TI  - Pharmacological control of cellular calcium handling in dystrophic skeletal
      muscle.
AB  - Duchenne muscular dystrophy arises due to the lack of the cytoskeletal protein
      dystrophin. In Duchenne muscular dystrophy muscle, the lack of dystrophin is
      accompanied by alterations in the dystrophin-glycoprotein complex. We and others
      have found that the absence of dystrophin in cells of the Duchenne muscular
      dystrophy animal model, the mdx mouse, leads to elevated Ca(2+) influx and
      cytosolic Ca(2+) concentrations when exposed to stress. We have also shown that
      alpha-methylprednisolone, the only drug used successfully in the therapy of
      Duchenne muscular dystrophy, and creatine lowered cytosolic Ca(2+) levels in mdx
      myotubes. It is likely that chronic elevation of [Ca(2+)] in the cytosol in
      response to stress is an initiating event for apoptosis and/or necrosis in
      Duchenne muscular dystrophy or mdx muscle and that alterations in mitochondrial
      function and metabolism are involved. Other cellular signalling pathways (e.g.
      nitric oxide) might also be affected.

PMID- 12206812
TI  - Considerations to the policy of future clinical therapeutic trials in DMD.
AB  - In spite of rapidly increasing insight into the molecular basis of neuromuscular
      diseases, treatment still relies on convention and clinical studies. Experience
      with a multicentre double blind treatment study in Duchenne muscular dystrophy
      and with consecutive steroid treatment documentation for up to 8 years enables us
      to identify a series of crucial points on which to focus while planning such
      clinical trials. The most important seem to be: a carefully structured, detailed
      study, clear-cut aims and objectives, expertise of investigators, sufficient
      training of examiners, and careful monitoring. If patients with neuromuscular
      diseases are treated outside structured studies, their course should be monitored
      comparably. Examples of the impact of such documentation are available from the
      ongoing German multicentre trial on the treatment of Duchenne muscular dystrophy.

PMID- 12206811
TI  - Steroids in Duchenne muscular dystrophy: from clinical trials to genomic
      research.
AB  - Steroids represent the only pharmacological palliative treatment for Duchenne
      muscular dystrophy. However, they do have side effects and despite a large number
      of published studies showing their efficacy, they are still not universally used.
      This is largely due to the lack of functional outcome and quality of life
      measures in most of the published studies and suggests that further trials might
      be required to answer some of the still unclear aspects of their role. Another
      important aspect of steroid therapy in Duchenne dystrophy is that we do not know
      how they work in dystrophic muscle. We have initiated a collaborative study on
      gene profiling using microarray in steroid-treated mdx mice. cDNA microarray
      studies were performed to examine the levels of skeletal muscle gene expression
      in a pool of mdx mice treated with prednisolone for 1 and 6 weeks. Interesting
      preliminary data on untreated mdx mice suggest that the gene profiling of young
      (7 weeks) versus older (12 weeks) mice is very significantly different.
      Furthermore, a large number of genes showed significant changes in expression at
      the mRNA level on treatment with prednisolone. These included structural protein
      genes; signalling genes and genes involved in immune response. Hopefully,
      analysis of this pattern of steroid-induced gene expression will provide some
      insight into understanding how glucocorticoids improve strength in Duchenne
      dystrophy, and may help in developing more effective and less toxic therapeutic
      approaches.

PMID- 12206813
TI  - An effective, low-dosage, intermittent schedule of prednisolone in the long-term
      treatment of early cases of Duchenne dystrophy.
AB  - The aim of this study was to evaluate the long-term effects in young children
      with Duchenne dystrophy of an intermittent low dosage regime of prednisolone
      (0.75 mg/kg per day for 10 days per month, or 10 days on and 10 days off). Six
      children under 5 years with Duchenne dystrophy have been commenced on this
      schedule, four of whom have been followed for at least 30 months and are reported
      here. All four presented with classical Duchenne dystrophy, and had an out-of
      frame deletion in the Duchenne gene and absence of dystrophin in their muscle.
      All four showed a rapid and dramatic response in muscle function and strength. In
      three of the four there was an almost complete remission of all clinical signs of
      dystrophy. Their functional scores remained well above the average scores
      recorded in untreated Duchenne boys at the same age. There was no increase in
      weight, stunting of growth, decreased bone density or any other significant side
      effects related to the prednisolone. Our current experience suggests that this
      intermittent, low-dosage prednisolone regime is well tolerated and can be safely
      given long-term in young children with Duchenne dystrophy. The striking response
      also suggests that there may be an optimal window for treatment of Duchenne
      dystrophy in the early stages of the disease.

PMID- 12206814
TI  - Effect of nordihydroguaiaretic acid on intracellular Ca(2+) concentrations in
      hepatocytes.
AB  - The effect of nordihydroguaiaretic acid (NDGA) on Ca(2+) signaling in human
      hepatoma cells (HA22/VGH) has been investigated. NDGA (5-50 microM) increased
      [Ca(2+)](i) concentration-dependently. The [Ca(2+)](i) increase comprised an
      initial rise and an elevated phase over a time period of 4 min. Removal of
      extracellular Ca(2+) reduced 10-50 microM NDGA induced [Ca(2+)](i) signals by
      45+/-5%. Consistently, the 50 microM NDGA-induced [Ca(2+)](i) increase in Ca(2+)
      containing medium was reduced by 41+/-2% by 10 microM of La(3+), nifedipine or
      verapamil. In Ca(2+)-free medium, pretreatment with 20 microM NDGA for 6 min
      abolished the [Ca(2+)](i) increase induced by the endoplasmic reticulum Ca(2+)
      pump inhibitor thapsigargin (1 microM). Conversely, 20 microM NDGA failed to
      increase [Ca(2+)](i) after 1 microM thapsigargin had depleted the endoplasmic
      reticulum Ca(2+) store. Inhibition of phospholipase C with 2 microM U73122 had
      little effect on 20 microM NDGA-induced Ca(2+) release. Several other
      lipoxygenase inhibitors had no effect on basal [Ca(2+)](i). Together, the data
      suggest that NDGA increased [Ca(2+)](i) in hepatocytes in a lipoxygenase
      independent manner, by releasing Ca(2+) from the endoplasmic reticulum and
      causing Ca(2+) influx.

PMID- 12206815
TI  - Main targets of tetraaza macrocyclic copper complex on L1210 murine leukemia
      cells.
AB  - Several metal complex agents have already been introduced into clinical tumor
      therapy and others are subject of antitumor studies. In this study we focused on
      the tetraaza macrocyclic copper complex (Cu(TAAB)Cl(2)). We studied the influence
      of the substance on cell growth, cell cycle, membrane integrity, necrosis,
      apotosis and glutathione level on the leukemic cell line L1210 in 1-day (22 h)
      and 3-day (72 h) experiments. The metal complex shows a dose-dependent
      antiproliferative effect, without affecting cell cycle phases. The present
      results confirm that copper complex can damage plasmatic membranes and trigger
      apoptosis, and that after treatment of leukemic cells with the copper complex,
      glutathione levels were increased.

PMID- 12206816
TI  - The in vitro effects of Pb acetate on NO production by C6 glial cells.
AB  - The CNS neurotoxic effects of lead (Pb) are well documented; however, the
      molecular toxicity targets have not been clearly delineated. Astroglial cells,
      which are the most abundant cells in the brain and provide critical support to
      the neurons, are known to accumulate Pb. Although NO generated by inducible NO
      synthase (iNOS) in glial cells has been associated with many neurotoxic events,
      it can also serve to protect by modulating blood flow, increase antimicrobial and
      tumoricidal activities, and promote immune responses following injury or insult.
      The present investigations were designed to test the hypothesis that Pb exposure
      may perturb cytokine signal transduction pathways leading to NO production by
      astroglial cells. Pretreatment with Pb acetate (500 nM-10 microM) attenuated the
      generation of NO in a concentration-dependent manner up to 90%, and suppressed
      iNOS protein expression, as well as interfered with the homeostatic functions of
      calcium in the cytokine-induced NO signal transduction pathway. In addition,
      pretreatment with staurosporine, a serine-threonine kinase inhibitor, or KT5720,
      a specific protein kinase A inhibitor (PKA), inhibited cytokine-induced NO
      production in a concentration-dependent manner with IC(50) values of 26.3 and
      346.7 nM, respectively. Therefore, Pb may impede events within the PKA signal
      transduction pathway; although, based on results from a gel shift assay, Pb does
      not directly affect PKA enzyme activity. Taken together, these results suggest
      the possibility that the suppressive effect of Pb acetate on cytokine-induced NO
      production in glial cells may be implicated in the neurophysiologic changes noted
      following occupational or environmental exposure to Pb.

PMID- 12206817
TI  - Pretreatment of rats with the inducing agents phenobarbitone and 3
      methylcholanthrene ameliorates the toxicity of chromium (VI) in hepatocytes.
AB  - To exert cytotoxicity chromium VI (Cr(VI)) has to be reduced inside cells. This
      is achieved through both enzymatic and non-enzymatic mechanisms. Enzymatic
      mechanisms include DT-diaphorase, cytochrome P450, and NADPH cytochrome c
      reductase, and non-enzymatic mechanisms involve reduced glutathione (GSH) and
      ascorbic acid. The extent of cytotoxicity of Cr(VI) may thus be influenced by the
      availability of non-enzymatic reductants, and by the activities of the reductase
      enzymes. In the present paper we have investigated the effect of pretreatment
      with the inducing agents, phenobarbitone (PB) and 3-methylcholanthrene (3-MC), on
      the response of rat hepatocytes to Cr(VI). Pretreatment with PB increased the
      activity of NADPH cytochrome c reductase, and 3-MC increased DT-diaphorase
      activity in hepatocytes. Both inducers increased cytochrome P450 content, while
      neither influenced intracellular GSH content or the activity of glutathione
      reductase. Pretreatment with either PB or 3-MC resulted in amelioration of Cr(VI)
      toxicity both in terms of hepatocyte viability, and to a greater extent, in terms
      of Cr(VI) induced GSH loss. We propose that the inducing agents increase the
      amount of enzymatic reduction of Cr(VI) relative to non-enzymatic reduction.
      Thus, less GSH is used in the reduction of Cr(VI), and intracellular GSH does not
      fall as rapidly as in cells from control animals therefore cell integrity is
      better maintained. Exposure to environmental inducing agents in vivo may also
      alter the response of human tissues to Cr(VI).

PMID- 12206818
TI  - The immunomodulatory effects of the herbicide simazine on murine macrophage
      functions in vitro.
AB  - We examined the immunomodulating effects of simazine, a triazine herbicide, on
      murine peritoneal macrophages after in vitro pre-exposure. When thioglycollate
      elicited macrophages pre-exposed to simazine were stimulated with
      lipopolysaccharide (LPS), the antitumor activity induced by LPS was suppressed by
      simazine. Simazine also inhibited poly I:C-induced antiviral activity and
      interferon (IFN) production in macrophages. In addition, the production of nitric
      oxide (NO) and tumor necrosis factor-alpha (TNF-alpha) which have been known to
      be major effector molecules in macrophage-mediated cytotoxicity was decreased by
      simazine pretreatment in a dose-dependent manner. However, simazine had little
      effect on phagocytosis and the level of hydrogen peroxide (H(2)O(2)), interleukin
      1 (IL-1) and IL-6 by LPS-stimulated macrophages. Taken together, these data
      indicate that simazine has a differential immunomodulating effect on macrophage
      secretory and cellular activities.

PMID- 12206819
TI  - Acute effects of aflatoxins on guinea pig isolated ileum.
AB  - Previous studies on the aflatoxins have focused mainly on their chronic toxic
      effects. In this study we investigated the acute gastrointestinal effects of four
      common aflatoxins on isolated guinea pig ileum. AFB(1) (EC(50) 4.6+/-0.4 microM)
      and AFB(2) (EC(50)17+/-4.4 microM) contracted isolated guinea pig ileum in a dose
      dependent manner, whereas AFG(1) and AFG(2) evoked no contractions. Atropine (5.9
      nM 11.8 and 23.6 nM) antagonized AFB(1)-induced contractions in a dose-dependent
      manner. Pretreatment with the nicotinic ganglionic blocker, hexamethonium (up to
      55 microM), left AFB(1)-induced contractions unchanged. In contrast, tetrodotoxin
      (0.3 microM), blocked AFB(1) contractile activity. The two inhibitors of ACh
      release, morphine (0.3 microM) and clonidine (0.4 microM), antagonized EC(50)
      AFB(1)-induced contractions, and apamin, a drug that increases neuronal
      excitability, facilitated the EC(50) AFB(1)-induced contractile effect. The
      choline uptake blocker, hemicholinium (17.4 microM) markedly reduced AFB(1)
      induced contractions. These results suggest that aflatoxins induce their
      contractile effect indirectly through the cholinergic system by stimulating
      acetylcholine release from the postganglionic parasympathetic nerve endings. The
      acute actions of aflatoxins on isolated guinea pig ileum could explain their
      acute gastrointestinal effects in humans and animals.

PMID- 12206820
TI  - Inhibition of vacuolation toxin activity of Helicobacter pylori by iodine,
      nitrite and potentiation by sodium chloride, sterigmatocystin and fluoride.
AB  - The toxin VacA produced by Helicobacter pylori is an important determinant of
      virulence. VacA causes vacuolation of cultured cells such as HeLa cells. Iodine,
      nitrite, sodium chloride, thiocyanate and fungus toxin sterigmatocystin are
      universally present in nature and could possibly be related to carcinogenesis of
      the stomach. The present study was designed to examine the effects of the above
      mentioned compound on VacA-induced vacuolation of HeLa cells, which was
      quantitated using the neutral red uptake assay. VacA-induced vacuolation was
      inhibited by BafA1 and NPPB. Formation of large vacuoles was inhibited in the
      presence of iodine, nitrite, but enhanced by sodium chloride, thiocyanate,
      fluoride and sterigmatocystin. Our results indicate that VacA toxin may interact
      with other gastric cancer risk factors present naturally in the environment, and
      suggest that those compounds may modulate the development of gastric cancer
      induced by H. pylori.

PMID- 12206821
TI  - Effects of hexachlorobenzene on embryonic mammalian cells.
AB  - Hexachlorobenzene (HCB) is a persistent organic pollutant that has been found to
      be bioaccumulating in several Arctic regions of the world. The response of
      embryonic cells to HCB exposure has been evaluated for several different
      cytotoxic responses, including genotoxic effects. NIH 3T3 (mouse) and WS1 (human)
      embryonic cells were exposed to HCB at 1 and 10 times the average newborn cord
      blood concentrations of Alaska Arctic natives. Assays were then performed to
      determine the subsequent effects of HCB on overall cell number, viability, cell
      growth fraction and long-term survival, as well as specific biochemical and
      molecular responses. Exposure of both cell types to HCB results in cell membrane
      damage, a short-term decrease in cell number, increased DNA strand breaks, and a
      long-term decrease in colony survival. WS1 cells also undergo cell-cycle arrest
      and modulations in glutathione concentration after exposure to HCB. In addition,
      NIH 3T3 cells exhibit an increased number of transformed foci after repeated
      exposure to HCB. This study demonstrates that relevant environmental
      concentrations of HCB have significant effects on mammalian embryonic cells in
      culture.

PMID- 12206822
TI  - Sulfation of bisphenol A abolished its estrogenicity based on proliferation and
      gene expression in human breast cancer MCF-7 cells.
AB  - Bisphenol A, an endocrine-disrupting chemical, is widely used in many consumer
      products. We previously showed the sulfoconjugation of bisphenol A catalyzed by a
      human thermostable phenol sulfotransferase, ST1A3. The estrogenic potency of
      bisphenol A sulfate was compared with that of bisphenol A by an E-screen assay
      using human breast cancer MCF-7 cells. An increase in the expression level of an
      estrogen-responsive pS2 gene was also examined using MCF-7 cells after exposure
      to bisphenol A and its sulfate for their estrogenicity. Bisphenol A sulfate did
      not exhibit estrogenic effects at 0.1 microM (E-screen assay) and 1 mM (pS2 gene
      expression) compared with bisphenol A, which exhibited the effects at 3 nM (E
      screen assay) and 1 microM (pS2 gene expression), respectively. We have therefore
      evaluated major roles of cytosolic phenol sulfotransferase in the human liver.
      Bisphenol A sulfation in human liver cytosols was inhibited by more than 90% by p
      nitrophenol and quercetin, a typical substrate and specific inhibitor of phenol
      sulfotransferase, respectively. These results indicated that the estrogenicity of
      bisphenol A was abolished through its sulfation catalyzed by a human hepatic
      thermostable phenol sulfotransferase.

PMID- 12206823
TI  - Predictive ability of reconstructed human epidermis equivalents for the
      assessment of skin irritation of cosmetics.
AB  - The aim of this study was to examine the concordance between human in vivo and in
      vitro skin irritation classifications of cosmetic products and to evaluate the
      correlations between the different parameters. For that purpose, 22 formulations
      from product development test series, covering the full range of in vivo scores
      and representing different cosmetic product classes, were tested in vivo
      (modified Frosch-Kligman Soap Chamber Patch Test with repetitive occlusive
      application) and in vitro using two epidermis equivalents commercially available
      as kits (EpiDerm and EPISKIN) and one in-house model (Cosmital). In vivo, skin
      reactions (erythema, dryness and fissures) were visually evaluated and, in
      addition, skin redness and transepidermal water loss (TEWL) were measured by
      means of technical instruments. The parameters measured in vitro were the percent
      cell viability in the MTT reduction assay, with ET(50) determination, and the
      extracellular release of the pro-inflammatory mediator IL-1alpha and of the
      cytosolic enzyme lactate dehydrogenase (LDH), into the culture medium collected
      after topical application of the products for different exposure times (time
      course assay). In general, good Spearman rank correlations could be observed
      between the different in vivo parameters (with the exception of TEWL and dryness
      at day 2). Furthermore, high correlation coefficients were obtained by comparing
      the different in vitro parameters (except for LDH release) and different models,
      which allowed to conclude that the results obtained with the different
      reconstructed epidermis models were very similar. A comparison between in vivo
      and in vitro parameters resulted in the best rank correlation for ET(50), then in
      decreasing order, for the percent MTT viability at 16 h, the IL-1alpha release
      and finally, for LDH release, where the correlation was generally low. A direct
      comparison of the mean total scores (sum of erythema, dryness and fissures at day
      5) of the 22 products with the best predictor, ET(50) obtained with the three
      reconstructed epidermis models, using simple linear regression analysis resulted
      in a coefficient of correlation R=0.94 for EpiDerm, R=0.90 for Cosmital and
      R=0.84 for EPISKIN. Multivariate descriptive statistics showed that the in vitro
      parameters, MTT viability evaluated after the 16-h exposure and ET(50), as well
      as the in vivo parameters, sum of visual scores at day 5 and chromameter value,
      were the best endpoints to discriminate between irritant and non-irritant
      products. Using the in vivo mean total scores at day 5 with a cut-off value at 2
      and the in vitro percent MTT viability after the 16-h exposure with a cut-off
      value at 50% to classify the products, the same two-by-two contingency table was
      obtained for all the three reconstructed epidermis models with sensitivity=92%,
      specificity=100% and observed concordance=95% (kappa=0.91; 95% confidence
      interval 0.74-1.08). This classification system was a satisfactory and relevant
      approach to discriminate the "irritant" from the "non-irritant" cosmetic products
      in this study. In conclusion, this study demonstrated the usefulness of
      reconstructed human epidermis equivalents for the in vitro assessment of the
      irritation potential of a series of cosmetic products. These models allow the
      measurement of quantifiable and objective endpoints relevant to in vivo
      irritative phenomena.

PMID- 12206824
TI  - Colorimetric quantitation of in vitro cell density using carmine, a chromosome
      specific stain.
AB  - Cell number is usually evaluated during in vitro studies to estimate metabolic or
      pharmacological effects of specific compounds. However, estimation of in vitro
      cell density by direct cell counting is a laborious and time-consuming task,
      whereas indirect methods for cell quantitation have serious disadvantages such as
      environmental costs or inaccuracies derived from non-specific interferences. We
      developed a new method for in vitro cell density quantitation which employs
      carmine, a natural dye widely used for chromosome staining in cytological
      studies. Normal or transformed murine fibroblasts, avian normal fibroblasts,
      human epithelial HeLa cells, and insect cells, inoculated at a range of cell
      densities, were fixed with 4% formaldehyde/PBS and stained with 0.4% alcoholic
      HCl carmine. The stain retained in cell monolayers was extracted with 0.01 M NaOH
      and spectrophotometrically measured at 531 nm. Invariably, high correlation
      coefficients between cell number and absorbance were obtained for each cell type,
      within a range of 5 x 10(3) to 5 x 10(5) cells. Moreover, identical cell growth
      curves were obtained when cell number was estimated over several days of culture
      by both direct cell counting and carmine staining methods. Our results show that
      the carmine staining method represents an easy, precise and reliable alternative
      for in vitro cell quantitation, avoiding interferences caused by cell components
      modulable by culture treatments, and over a wide range of cell types and cell
      densities.

PMID- 12206825
TI  - An in vitro model for detecting skin irritants: methyl green-pyronine staining of
      human skin explant cultures.
AB  - We evaluated the potential of human organotypic skin explant cultures (hOSECs)
      for screening skin irritants. Test chemicals were applied to the epidermis of the
      skin explants which were incubated for 4, 24 or 48 h in tissue culture medium. A
      decrease in epidermal RNA staining, visualised in frozen sections using a
      modified methyl-green pyronine (MGP) staining procedure, was used as a marker of
      irritancy. A decrease in epidermal RNA after a 4-, 24- or 48-h exposure to a
      certain concentration of a test chemical equated to a MGP score of 3, 2 or 1,
      respectively. The MGP score was 0 if there was no keratinocyte cytotoxicity after
      a 48-h exposure. A minimum of three donors were used per chemical and the average
      MGP score was used to classify the chemical as irritant or not. Chemicals with an
      average MGP score > or =1.5 were classified as irritants (R38), at that
      concentration. Chemicals with a MGP score <1.5 were not classified (NC), at that
      concentration. The results obtained using human skin in vitro were compared with
      published data obtained using cultured porcine skin, the cutaneous Draize test
      (from this point referred to as the "rabbit skin irritation test") and volunteer
      studies. There was an excellent correlation between the classification of a
      chemical, as R38 or NC, based on hOSEC and results of volunteer studies. The
      hOSEC model predicted perfectly the irritation hazard of the 22 chemicals for
      which volunteer data were available. The porcine OSEC correctly predicted the
      classification of 21 of 22 (95%) chemicals and the rabbit skin irritation test
      correctly predicted the classification of 14 of 15 chemicals (93%) for which data
      were available. In conclusion, MGP staining of human skin explant cultures can be
      used to predicted human skin irritancy in vivo. In addition, the data validate
      the use of porcine skin as an alternative to human skin for screening for dermal
      irritants in vitro.

PMID- 12206826
TI  - The use of quantitative image analysis in the assessment of in vitro
      embryotoxicity endpoints based on a novel embryonic stem cell clone with endoderm
      related GFP expression.
AB  - The capacity of pluripotent embryonic stem cells (ESC) to differentiate in vitro
      into various tissues provides the opportunity to develop an in vitro assay for
      investigating mechanisms of developmental toxicity. ESC clones carrying tissue
      specific reporter gene constructs are currently being developed. The clones
      should allow the quantification of the effects of chemicals on the development of
      germ layers and main target tissues. We report the establishment of the alpha
      fetoprotein_GFP/D3 reporter gene clone: alpha-fetoprotein (AFP) enhancers and the
      homologous promoter regulate green fluorescent protein (GFP) expression in cells
      of the D3-ESC clone. AFP was used as a marker for endodermal cells.
      Differentiation of this clone via embryoid bodies (EBs, spheroids of cells) leads
      to green fluorescence on the surfaces of EBs. AFP- related GFP expression was
      confirmed. An easy and quick image analysis-based endpoint measurement was
      developed for quantifying low amounts of cells expressing GFP. As demonstrated
      with the embryotoxic chemical diphenylhydantoin, image analysis can be used to
      distinguish between a general effect on EB growth and a specific effect on the
      development of GFP-positive endodermal cells. Endoderm development was inhibited
      at a different dose than cardiomyocyte development.

PMID- 12206827
TI  - Evaluation of eight in vitro assays for assessing the cytotoxicity of cigarette
      smoke condensate.
AB  - The accurate assessment of cytotoxicity is important for evaluating the potential
      of a test agent to induce pathologies that result from cell killing and to
      determine appropriate doses for other endpoints, such as genetic toxicology
      studies. The objective of this work was to determine the most sensitive assays
      for assessing cytotoxicity in Chinese hamster ovary (CHO) cells following short
      term (1 h) and long-term (24 h) exposure to cigarette smoke condensate (CSC).
      Eight in vitro cytotoxicity assays with different endpoints were used to evaluate
      the cytotoxicity of Kentucky reference 1R4F (K1R4F) CSC in CHO cells. The assays
      used for this study were neutral red uptake, LDH release, kenacid blue binding,
      MTT formation, XTT formation, acid phosphatase activity, sulforhodamine B binding
      and resazurin binding. Four of the more widely used cytotoxicity assays (neutral
      red, MTT, kenacid blue and LDH) were also evaluated at 3-, 6-, 12- and 18-h time
      points. At the 1-h exposure time, LDH was the most sensitive with toxicity
      observed beginning at 100 microg/ml. None of the other assays demonstrated a
      concentration-dependent increase in toxicity after 1-h exposures even at the
      maximum concentration of 150 microg/ml of CSC. Following 24 h of exposure,
      neutral red and kenacid blue were the most sensitive. The results of our study
      indicate the assay that measured membrane integrity was the most sensitive for
      short exposure times, whereas the neutral red and kenacid blue assays that
      measured total cell number were more sensitive for longer exposure times.

PMID- 12206828
TI  - Measurement of the intracellular distribution of reduced glutathione in cultured
      rat hepatocytes using monochlorobimane and confocal laser scanning microscopy.
AB  - Intracellular reduced glutathione (GSH) plays a key role in protecting cells from
      toxicity by maintaining intracellular redox status, conjugating with
      electrophilic xenobiotics and free radicals, and detoxifying reactive peroxides.
      Several toxic chemicals interact with GSH during their metabolism, and in many
      cases it would be advantageous to monitor intracellular GSH distribution during
      that process. We present a novel method to monitor intracellular GSH levels
      utilising a new laser light source, InGaN laser, for confocal microscopy and
      fluorescent detection of monochlorobimane (mBCl) binding to GSH. The sensitivity
      of the method was compared with that obtained using o-phthalaldehyde (OPT) as a
      fluorochrome. In the presence of a source of glutathione S-transferase (GST),
      mBCl was specific for GSH, forming a fluorescent conjugate that was retained in
      hepatocytes for at least 35 min. mBCl was able to detect the GSH depleting
      effects caused by progressive inhibition of GSH synthesis by increasing
      concentrations of buthionine sulfoximine. It effectively monitored the rapid
      effects of menadione and chromium VI metabolism on intracellular GSH levels in
      the cytosol and nuclear compartments of the cells. The combination of a specific
      stain, a novel laser light source and confocal microscopy provide a valuable
      system for mechanistic studies of intracellular GSH distribution in toxicology
      studies.

PMID- 12206829
TI  - A redesigned corneal holder for the bovine cornea opacity and permeability assay
      that maintains normal corneal morphology.
AB  - The bovine cornea opacity and permeability assay (BCOP) has been in use for
      nearly 10 years but has not been submitted for regulatory approval. In previous
      reports we have presented corneal hydration and endothelial damage as additional
      endpoints in this assay and have suggested that the design of the BCOP's corneal
      holder should be modified. The standard holder used in the BCOP assay induces
      physical damage to the cornea because it contacts clear cornea causing edge
      damage to the epithelial, stromal and endothelial layers. Second, by forcing a
      curved, oval-shaped bovine cornea into a flat, circular opening, corneal
      wrinkling occurs which can alter the cornea's optical characteristics and, most
      importantly, induces endothelial damage. We now report on a redesigned BCOP
      corneal holder that clamps onto the sclera, maintains normal corneal shape and
      does not cause damage to the endothelium. This ensures that irritancy tests are
      conducted using healthy, anatomically normal tissue. Tests of this holder using
      acetone, trichloroacetic acid, isopropanol and benzalkonium chloride show that it
      is now possible to evaluate effects of chemical substances on the endothelium.
      The effects of these compounds on corneal opacity and hydration in the new holder
      are similar to their effects on the cornea in the standard holder.

PMID- 12206830
TI  - Quantitative determination of OH radical generation and its cytotoxicity induced
      by TiO(2)-UVA treatment.
AB  - Titanium dioxide (TiO(2)) has been reported to produce OH radical under
      ultraviolet-A (UVA) irradiation and to induce cytotoxicity. Various crystal forms
      and sizes of TiO(2) with UVA irradiation from OH radical generation was analysed
      spin trapping-X band (electron-spin resonance (ESR) spectroscopy. The amount of
      OH radical was determined with ESR signal intensity of the adducts in which OH
      radical was trapped with the spin-trapping reagent dimethyl pyrroline-N-oxide
      (DMPO). The formation of OH radicals varied in both crystal size and form of
      TiO(2). Irradiation of the anatase form of TiO(2) produced large numbers of OH
      radical in TiO(2) and UVA in a dose-dependent manner, but rutil form (90 nm in
      size) showed less OH radical generation. The crystal size had large influence on
      OH radical generation, but the optimum size for the OH radical generation was
      different between both forms. The UVA absorption spectrum of TiO(2) differed in
      regard to crystal size and form of TiO(2), but no relation was observed between
      UVA absorbency and OH radical formation. The cytotoxicity of TiO(2)-UVA
      irradiation was determined against Chinese hamster ovary (CHO) cells and a
      significant relationship was obtained between the cytotoxicity and the OH
      generation. Measurement of the amount of OH radical production by UVA irradiation
      with ESR is needed to clarify the effect of crystal form or sizes of TiO(2) on OH
      radical production and cytotoxicity.

PMID- 12206831
TI  - Turkey and chicken interleukin-18 (IL18) share high sequence identity, but have
      different polyadenylation sites in their 3' UTR.
AB  - The cDNA of turkey interleukin-18 (IL18) was cloned, initially using
      oligonucleotide primers based on the sequence of the chicken IL18 gene. The
      coding regions of the turkey and chicken IL18 genes are highly conserved (96.1%
      nucleotide identical and 97.4% amino acid identical). The 3' UTR of the turkey
      IL18 mRNA contains two 'instability' motifs and a canonical polyadenylation site,
      as compared to the chicken IL18 mRNA which contains only one instability motif
      and lacks a canonical polyadenylation site. Phylogenetic analysis shows that
      turkey and chicken IL18 have diverged to a less extent than IL18 from closely
      related mammalian species. We predict that turkey and chicken IL18 will cross
      react in functional assays.

PMID- 12206832
TI  - Oligoclonal Peyer's patch follicles in the terminal small intestine of cattle.
AB  - In small ruminants, the development of B cells differs from that in mice or in
      man. The anti-body repertoire is expanded in the Peyer's patches of the terminal
      ileum where each B-cell follicle is found by a few cells. To investigate the
      amount of founder clones in bovine ileal follicles, we have used sex mismatched
      cattle twins. These animals are chimeric due to placental anastomoses. Y
      chromosome targeted in situ hybridization was used to trace donor-derived cells
      of the male genotype in a female recipient (called a freemartin). A strong
      clustering of lymphoid cells originating from either twin was seen in the ileal
      Peyer's patches (IPPs). Furthermore, the follicles displayed a low amount of
      immunoglobulin heavy chain gene configurations in comparison with the splenic or
      jejunal follicles. These findings strongly suggest that as in sheep, the B-cell
      follicles in cattle IPPs develop oligoclonally.

PMID- 12206833
TI  - IMGT, the international ImMunoGeneTics database: a high-quality information
      system for comparative immunogenetics and immunology.
AB  - IMGT, the international ImMunoGeneTics database (http://imgt.cines.fr), is a high
      quality integrated information system specializing in Immunoglobulins (IG), T
      cell Receptors (TR) and Major Histocompatibility Complex (MHC) of human and other
      vertebrates, created in 1989, by LIGM, at the Universite Montpellier II, CNRS,
      Montpellier, France. IMGT provides a common access to standardized data, which
      include nucleotide and protein sequences, oligonucleotide primers, gene maps,
      genetic polymorphisms, specificities, 2D and 3D structures. IMGT includes several
      databases (IMGT/LIGM-DB, IMGT/HLA-DB, IMGT/3Dstructure-DB), Web resources ('IMGT
      Marie-Paule page') which comprise IMGT Scientific Chart, IMGT Repertoire, IMGT
      Bloc-notes, IMGT Education, IMGT Aide-memoire and IMGT Index, and interactive
      tools (IMGT/V-QUEST, IMGT/JunctionAnalysis). These expertly annotated data on the
      genome, proteome, genetics and structure of the IG, TR and MHC are of high value
      for comparative genome evolution studies of the adaptative immune response.

PMID- 12206834
TI  - Comparative study on characteristics of lysozymes from the hemolymph of three
      lepidopteran larvae, Galleria mellonella, Bombyx mori, Agrius convolvuli.
AB  - Lysozymes were purified from the hemolymph of three immunized Lepidopteran
      larvae, Galleria mellonella, Bombyx mori, Agrius convolvuli to compare their
      physico-chemical properties and antibacterial activities with those of chicken
      lysozyme. Four lysozymes including the one from chicken had similar molecular
      masses and chromatographic behavior on reverse phase-high pressure liquid
      chromatography. Western blotting analysis using an antibody raised against G.
      mellonella revealed that lysozyme cross-reacted with two other insect lysozymes
      but not with commercial chicken lysozyme. Antibacterial activities of lysozymes
      were measured in two types of tests: radial diffusion assay and colony count
      assay. Our antibacterial tests revealed that all lysozymes have strong activities
      against Gram-positive bacteria and three insect lysozymes still retain a little
      potency against Gram-negative bacteria, while chicken lysozyme has no activity
      against Gram-negative bacteria. Taken together, we conclude three Lepidopteran
      lysozymes have a common distinct structure and have an antibacterial activity,
      which is absent in chicken lysozyme, against Gram-negative bacteria.

PMID- 12206835
TI  - Characterization and partial purification of a lectin from the hemolymph of the
      white shrimp Litopenaeus schmitti.
AB  - The agglutinating activity of the hemolymph of Litopenaeus schmitti is
      insensitive to calcium and specific for acetylated sugars, particularly sialic
      acid (Neu5Ac) and O-sialoglycoconjugates (bovine submaxillary mucin) and has
      varying specificity for different LPS, which may suggest a putative role in
      microorganism recognition. Affinity chromatography on fetuin-agarose of the
      agglutinin resulted in a 220 kDa band (lectin), and a 82.5 kDa band, which
      probably is hemocyanin. The 220 kDa protein consists of 31 and 34 kDa subunits,
      suggesting that this lectin is multimeric. The lectin molecular mass was
      estimated by gel filtration to be 153+/-10 kDa. The hemolymph of L. schmitti
      comprises at least another soluble lectin, with distinct chemical and
      carbohydrate specificity than the 220 kDa lectin.

PMID- 12206836
TI  - Metabolism of oxidized and chemically modified low density lipoproteins in
      rainbow trout--clearance via scavenger receptors.
AB  - Oxidative modifications of low density lipoprotein (LDL) convert LDL into a
      ligand recognized by a variety of scavenger receptors (SR) in mammals. This
      oxidized LDL (oxLDL) activate several cell types, and have been shown to induce
      expression of a variety of genes in mammals. Lipoproteins of poikilothermic
      animals like salmonid fishes contain high levels of polyunsaturated fatty acids
      susceptible to oxidative modifications. We have investigated, and found trout LDL
      to be susceptible to oxidation in the presence of Cu(2+). When oxidized or
      acetylated trout LDL was injected intravenously, the clearance rate was increased
      compared to that of native LDL. Modified LDL was taken up almost exclusively in
      the kidney, whereas native LDL was also taken up in the liver. Uptake of both
      oxLDL and acetylated LDL in the kidney was significantly inhibited by
      lipoteichoic acid (LTA) and formaldehyde treated BSA (fBSA), both of which are
      known ligands of SR.

PMID- 12206837
TI  - Xenopus class II A genes: studies of genetics, polymorphism, and expression.
AB  - The amphibian Xenopus laevis has been a central model for the study of evolution
      of the major histocompatibility complex (MHC). Many of the counterparts of
      mammalian MHC genes have been identified in Xenopus, facilitating the
      understanding of MHC structure and function. Herein we characterize X. laevis MHC
      class II-alpha chain genes. There are three related class II A genes/haplotype in
      the four commonly used partially inbred strains, all of which linked to the
      functional MHC. At least two of these genes in the f haplotype encode full-length
      cDNA clones and a genomic fragment encoding the immunoglobulin-like domain of the
      third gene was also characterized. The protein structure and domain organization
      deduced from the two f/f cDNA clones are similar to mammalian MHC class II-alpha
      chains. Expression of class II A genes is highest in the spleen and intestine,
      similar to the previously examined tissue distribution of class II B genes. The
      two highly expressed genes display high sequence diversity among alleles, similar
      to what has been found in most other species. Surprisingly, transcript sizes of
      class II A alleles/isotypes are diverse, suggesting that Xenopus class II allelic
      lineages are very old.

PMID- 12206838
TI  - Initiation of humoral immunity. I. The role of cytokines and hormones in the
      initiation of humoral immunity using T-independent and T-dependent antigens.
AB  - The early events during the initiation of immune responses following the
      injection of T-independent (lipopolysaccharide, LPS) and T-dependent (bovine
      serum albumin, BSA) antigens were studied in immature male chickens.
      Specifically, the role of cytokines and hormones in the initiation of humoral
      immunity against these antigens was investigated. Both interleukin-1 (IL-1) and
      tumor necrosis factor (TNF-alpha) increased significantly post-LPS but not post
      BSA injection. While interleukin-2 (IL-2) significantly decreased post-LPS
      injection, IL-2 significantly increased post-BSA injection. Furthermore,
      corticosterone levels significantly increased and tri-iodothyronine (T(3)) levels
      significantly decreased post-LPS but not post-BSA injection. In this study, the
      results indicate that although LPS and BSA can induce a humoral antibody response
      in chickens, they activate different cytokines and neuroendocrine network
      systems.

PMID- 12206839
TI  - Initiation of humoral immunity. II. The effects of T-independent and T-dependent
      antigens on the distribution of lymphocyte populations.
AB  - The effect of injecting T-independent (lipopolysaccharide, LPS) and T-dependent
      (bovine serum albumin, BSA) antigens on the redistribution of lymphocyte
      populations in immature male chickens was investigated. In the blood, percentages
      of total T-cells (CD3+), T-helper cells (CD4+), and T-cytotoxic/suppressor cells
      (CD8+) significantly decreased post-LPS injection (PLI) but not post-BSA
      injection (PBI), while percentages of monocytes/thrombocytes (K1+) significantly
      increased PLI. Interleukin-1 receptor expression on blood lymphocytes increased
      significantly PLI and PBI. In the spleen, the percentages of total T-cells (CD3+)
      increased significantly PLI and PBI, macrophage (K1+) percentages increased
      significantly PLI, while B-cell percentages decreased significantly PLI. These
      results indicate that following antigen injection, there is a redistribution of
      peripheral blood lymphocytes (specifically T-lymphocytes) to secondary lymphoid
      organs and the kinetics and magnitude of the changes can differ according to the
      type of antigen used.

PMID- 12206841
TI  - Introduction. Recent scientific and technological advances have challenged the
      traditional treatment options for patients with localized prostate cancer.

PMID- 12206842
TI  - Targeted cryoablation of the prostate: 7-year outcomes in the primary treatment
      of prostate cancer.
AB  - The efficacy and safety of the long-term experience with targeted cryoablation of
      prostate cancer (TCAP) at a community hospital is retrospectively reviewed. A
      series of 590 consecutive patients who underwent TCAP as primary therapy with
      curative intent for localized or locally advanced prostate cancer from March 1993
      to September 2001 were identified. Patients were stratified into 3 risk groups
      according to clinical characteristics. Biochemical disease-free survival (bDFS),
      post-TCAP biopsy results, and post-TCAP morbidity were calculated and presented.
      The mean follow-up time for all patients was 5.43 years. The percentages of
      patients in the low-, medium-, and high-risk groups were 15.9%, 30.3%, and 53.7%,
      respectively. Using a prostate-specific antigen (PSA)-based definition of
      biochemical failure of 0.5 ng/mL, results were as follows: (1) the 7-year
      actuarial bDFS for low-, medium-, and high-risk patients were 61%, 68%, and 61%,
      respectively; (2) the bDFS probabilities for a PSA cutoff of 1.0 ng/mL for low-,
      medium-, and high-risk patients were 87%, 79%, and 71%, respectively; and (3) the
      bDFS probabilities for low-, medium-, and high-risk patients using the American
      Society for Therapeutic Radiology and Oncology (ASTRO) definition of biochemical
      failure (3 successive increases of PSA level) were 92%, 89%, and 89%,
      respectively. The rate of positive biopsy was 13%. After a positive biopsy, 32
      patients underwent repeat cryoablation. For those patients who underwent repeat
      cryoablation, 68%, 72%, and 91% remain bDFS using definitions of 0.5 ng/mL, 1.0
      ng/mL, and the ASTRO criteria, respectively, after a mean follow-up time since
      repeat cryoablation of 63 months. The rates of morbidity were modest, and no
      serious complications were observed. TCAP was shown to equal or surpass the
      outcome data of external-beam radiation, 3-dimensional conformal radiation, and
      brachytherapy. These 7-year outcome data provide compelling validation of TCAP as
      an efficacious treatment modality for locally confined and locally advanced
      prostatic carcinoma.

PMID- 12206843
TI  - Quality of life and sexuality of men with prostate cancer 3 years after
      cryosurgery.
AB  - The current study was designed to describe the long-term life quality and
      sexuality of men enrolled in a phase 2 clinical trial of cryosurgery for the
      treatment of localized prostate cancer. A total of 75 men were administered the
      Functional Assessment of Cancer Treatment-Prostate (FACT-P) before treatment and
      after treatment at 6 weeks, and at 3, 6, 12, 24, and 36 months. Additionally,
      these men completed a Sexuality Follow-Up Questionnaire (SFQ) 3 years after
      cryosurgery. By 12 months after cryosurgery, most FACT-P subscales had returned
      to pretreatment levels. Quality of life remained stable over the subsequent 2
      years. The only exception to this general trend was persistent impairment in
      measures of social/family well-being. At 36 months, 13% (5 of 38) of patients had
      regained erectile functioning, and an additional 34% (13 of 38) of patients were
      sexually active with the help of aids. The 3-year quality-of-life outcomes
      support the renewed interest in cryosurgery. No late complications were observed.
      Whereas improvements in erectile function were observed between years 1 and 3 for
      some patients, most continue to experience erectile dysfunction. For these
      patients, aids are an important adjunct to the treatment of their erectile
      dysfunction.

PMID- 12206844
TI  - Prostate cryoablation: a scientific rationale for future modifications.
AB  - This investigation was designed to identify potential directions for future
      modification of the percutaneous prostate cryoablation procedure. An analysis of
      prostate cancer location and volume in radical prostatectomy specimens was
      performed to evaluate the potential clinical consequences of these proposed
      modifications. A list of recommendations for improvements in the prostate
      cryoablation procedure was compiled from informal discussions held with
      participants in 9 training courses and conferences on prostate cryoablation over
      18 months. Subsequently, a population of 112 consecutive, sagittally sectioned
      whole-mount radical prostatectomy samples was evaluated for prostate cancer
      volume, number of individual foci, and location to examine the disease-specific
      outcomes of these proposed modifications. The most common areas for potential
      alterations in the current cryoablation technique include modifications that
      would further simplify the procedure, continue to reduce real and perceived
      toxicity, and augment efficacy. Importantly, modifications designed to reduce
      treatment side effects could conflict with efforts designed to improve
      eradication of prostate cancer. Pathologic analysis revealed multifocal cancer in
      79.5% of the samples, with 66% of cases exhibiting cancer within 5 mm of the
      urethra. The median volume of the index cancer was 1.6 cm3, whereas the median
      volume of the smaller ancillary lesions was 0.3 cm3. Prostate parenchymal-sparing
      alterations, proposed to reduce incontinence and erectile dysfunction by
      targeting the index cancer, would likely eradicate clinically significant cancer
      in 79% of men. The recent enthusiasm for prostate cryoablation as a reasonable
      minimally invasive treatment option for men with clinically localized cancer is
      likely to result in modifications of the established surgical technique.
      Knowledge of the anatomic location and cancer volume within the prostate gland is
      an important adjunct to planning such alterations. It is possible that
      parenchymal-sparing modifications to total gland prostate cryoablation can
      eradicate clinically significant cancer in most men, with a reduction in toxicity
      and cost.

PMID- 12206845
TI  - The evolution and state of modern technology for prostate cryosurgery.
AB  - Cryosurgery is the in situ ablation of a target tissue by application of extreme
      cold temperature. The ability of cryosurgery to ablate tissue is unquestioned. It
      is the controlled application of a cryoinjury in a manner to minimize morbidity
      that is problematic. Prostate cryosurgery is complicated by the proximity of the
      prostate to adjacent structures that are sensitive to a freeze injury, namely the
      urethra, rectal wall, and neurovascular bundles. Several recent technological
      advances have led to the development of an effective treatment protocol with
      acceptable morbidity. These include the advent of real-time transrectal
      ultrasound, cryomachines with almost instant freeze-thaw control through the use
      of the Joule-Thompson effect, and warming catheters to effectively preserve the
      integrity of the urethra and external sphincter. Further, temperature monitoring
      at the posterior margin of the prostate sometimes combined with an injection of
      saline solution into Denonvilliers fascia has reduced the occurrence of
      urethrorectal fistula formation to 0% to 0.5% in modern series. We review the key
      innovations of prostate cryosurgery that differentiate this state-of-the-art
      procedure from that used by early investigators to even that of the early 1990s.
      Potential future innovations, specifically related to image guidance of the
      procedure, are also addressed.

PMID- 12206846
TI  - Cryosurgery as primary treatment for localized prostate cancer: a community
      hospital experience.
AB  - The technique and recent experience incorporating cryosurgery into our community
      practice for primary treatment of localized prostate cancer is described. Between
      December 2000 and December 2001, a total of 93 patients underwent targeted
      cryoablation for localized prostate cancer. Of the 93 patients, 18 had failed
      radiotherapy, and cryotherapy was used as salvage therapy. The remaining 75
      patients underwent targeted cryoablation of the prostate as primary therapy. A
      single urologist using an argon-based cryoablation system performed the
      procedure. Cryoprobes and thermosensors were placed under transrectal ultrasound
      guidance via a transperineal route. A double freeze-thaw cycle was used with
      anterior-to- posterior probe operation. Strategically placed thermosensors were
      used to monitor and control the freezing, and a warming catheter was used to
      protect the urethra. We achieved a nadir prostate-specific antigen level of < or
      =0.4 ng/mL in 84% of the entire population we studied (63 of 75 patients).
      Postsurgery complications were minimal. Incontinence developed in 4 patients, as
      did postsuprapubic catheter removal urinary retention. Erectile dysfunction
      developed in 28 of 34 patients who were potent preoperatively, with 6 of the 34
      patients regaining potency after surgery. No rectourethral fistula formation
      occurred. Urethral sloughing was observed in 5 patients, 1 of whom developed a
      scrotal abscess during treatment of the sloughing. The use of cryoablation of the
      prostate for the treatment of localized adenocarcinoma of the prostate is
      feasible and can easily be transferred from the pioneering centers to the
      community hospitals without sacrificing safety or efficacy.

PMID- 12206847
TI  - The cryobiology of cryosurgical injury.
AB  - Cryosurgery, or tissue destruction by controlled freezing, has been investigated
      as a possible alternative to surgical intervention in the treatment of many
      diseases. This technique, which is under the larger category of thermal therapy,
      has its origins in the 1800s when advanced carcinomas of the breast and uterine
      cervix were treated with iced saline solutions. Since those early times, this
      technique has been used routinely to treat malignancies on the surface of the
      body (ie, dermatologic tumors) and has gained some acceptance as a clinical tool
      for the management of internal malignancies, including carcinoma of the prostate
      and kidney. The main advantages of the technique are the potential for less
      invasiveness and lower morbidity compared with surgical excision. The study of
      the destructive process of freezing is the focus of this article and is divided
      into 2 main areas: (1) understanding the mechanism by which freezing destroys
      tissue, and (2) understanding the thermal history that causes tissue destruction.
      The term "thermal history," as used in this article, will mean the time
      temperature history experienced by the tissue during a thermal insult.

PMID- 12206848
TI  - Future directions for cryosurgery computer treatment planning.
AB  - Computer treatment planning for cryosurgery is an area of research and
      development that will greatly assist the practicing physician and will promote
      improved quality assurance for clinical procedures. Good planning and precision
      image-guided treatment delivery are complementary in achieving an optimal
      treatment outcome. State-of-the-art cryosurgery treatment planning systems are at
      an early stage of development in comparison with radiation treatment planning
      systems for external beams. Using 30 years of progress in the area of radiation
      treatment planning as a guide, this article presents a summary of the avenues for
      research and development in cryosurgery treatment planning that are likely to
      accelerate the practical application of precision cryosurgery to a broad spectrum
      of anatomical sites. Emphasis is placed on prostate cryosurgery, imaging
      techniques, and recommendations for manufacturers of these systems. Optimization
      of the clinical procedure in the planning stage using mathematical algorithms to
      define the positioning and operation of cryoprobes is discussed.

PMID- 12206849
TI  - Bosentan, a dual endothelin receptor antagonist, activates the pregnane X nuclear
      receptor.
AB  - Recent clinical studies have shown that bosentan, a dual endothelin receptor
      antagonist, decreases the exposure to various substrates of cytochrome P450 (CYP)
      isoenzymes 2C9 and 3A4. The aim of the study was to investigate the effect of
      bosentan, its metabolites and glibenclamide on the activity of the pregnane X
      receptor, a nuclear receptor that regulates the transcription of CYP3A4. CV-1
      monkey kidney cells were transiently transfected with a luciferase reporter
      plasmid containing three copies of the ER6 response element of CYP3A4 and the
      human or mouse pregnane X receptor. Subsequently, the cells were incubated with
      the test compounds and the activity of luciferase determined. Bosentan activated
      the human pregnane X receptor with an EC(50) of 19.9 microM, whereas rifampicin
      had an EC(50) value of 1.9 microM. Ro 47-8634 (4-tert-butyl-N-[6-(2-hydroxy
      ethoxy)-5-(2-hydroxy-phenoxy)-2,2'-bipyrimidin-4-yl]-benzenesulfonamide), a
      metabolite of bosentan, and glibenclamide also activated the pregnane X receptor.
      The findings provide a molecular mechanism for the interactions observed between
      bosentan and several drugs.

PMID- 12206850
TI  - The pharmacology of T-kinin and des-Arg(11)-T-kinin in primary cultures of rat
      bladder smooth muscle cells.
AB  - T-kinin and its putative carboxypeptidase product des-Arg(11)-T-kinin are members
      of the kinin family that are unique to the rat. Primary cultures of rat bladder
      smooth muscle cells were used to investigate the pharmacology of these peptides.
      Calcium imaging experiments showed that rat bladder smooth muscle cells responded
      to both bradykinin and des-Arg(9)-bradykinin with an increase in [Ca(2+)](i) and
      responses to both agonists could be observed in the same cell. A more detailed
      pharmacological characterisation with a range of bradykinin receptor agonists and
      antagonists using 45Ca(2+) efflux confirmed the presence of both B(1) and B(2)
      bradykinin receptors. Using this cellular model, we confirm that T-kinin is a
      bradykinin B(2) receptor agonist and show for the first time that des-Arg(11)-T
      kinin is a potent and selective bradykinin B(1) receptor agonist. In addition,
      using cells expressing the cloned rat and human bradykinin B(2) receptors plus
      the Ca(2+)-sensitive protein aequorin, T-kinin was shown to be selective for the
      rat over the human bradykinin B(2) receptor.

PMID- 12206851
TI  - Arachidonic acid release and prostaglandin F(2alpha) formation induced by
      anandamide and capsaicin in PC12 cells.
AB  - Anandamide, an endogenous agonist of cannabinoid receptors, activates various
      signal transduction pathways. Anandamide also activates vanilloid VR(1) receptor,
      which was a nonselective cation channel with high Ca(2+) permeability and had
      sensitivity to capsaicin, a pungent principle in hot pepper. The effects of
      anandamide and capsaicin on arachidonic acid metabolism in neuronal cells have
      not been well established. We examined the effects of anandamide and capsaicin on
      arachidonic acid release in rat pheochromocytoma PC12 cells. Both agents
      stimulated [3H]arachidonic acid release in a concentration-dependent manner from
      the prelabeled PC12 cells even in the absence of extracellular CaCl(2). The
      effect of anandamide was neither mimicked by an agonist nor inhibited by an
      antagonist for cannabinoid receptors. The effects of anandamide and capsaicin
      were inhibited by phospholipase A(2) inhibitors, but not by an antagonist for
      vanilloid VR(1) receptor. In PC12 cells preincubated with anandamide or
      capsaicin, [3H]arachidonic acid release was marked and both agents were no more
      effective. Co-addition of anandamide or capsaicin synergistically enhanced
      [3H]arachidonic acid release by mastoparan in the absence of CaCl(2). Anandamide
      stimulated prostaglandin F(2alpha) formation. These findings suggest that
      anandamide and capsaicin stimulated arachidonic acid metabolism in cannabinoid
      receptors- and vanilloid VR(1) receptor-independent manner in PC12 cells. The
      possible mechanisms are also discussed.

PMID- 12206852
TI  - Cyclooxygenase inhibitor modulation of dopamine-related behaviours.
AB  - The sequential action of phospholipase A(2) and cyclooxygenase leads to the
      production of prostaglandins in the brain, an event hypothesised to cause
      dopaminergic stimulation. To investigate this further, we examined the effect of
      the nonselective cyclooxygenase inhibitors indomethacin and piroxicam on several
      indices of dopaminergic function in adult male rats. Both drugs inhibited
      catalepsy induced by the dopamine D1-like receptor antagonist R(+)-7-chloro-8
      hydroxy-3-methyl-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine (SCH23390), the
      dopamine D2-like receptor antagonist raclopride and by haloperidol, findings in
      agreement with a dopaminergic effect of cyclooxygenase inhibitors. However,
      neither cyclooxygenase inhibitor had an effect upon disruption of prepulse
      inhibition of the auditory startle reflex by amphetamine or on the rate of
      amphetamine self-administration. Both drugs reduced amphetamine-stimulated
      locomotor activity. Our data indicate that the mechanism by which cyclooxygenase
      inhibitors alter motor behaviour is unlikely to be due to a simple direct action
      at the dopaminergic synapse. Their apparent ability to antagonise hypoactivity
      without generalised dopaminergic stimulation suggests that other, possibly
      multiple, neurotransmitter systems may be involved.

PMID- 12206853
TI  - Modulation of formalin-induced behaviors and edema by local and systemic
      administration of dextromethorphan, memantine and ketamine.
AB  - The present study examined the effects of local peripheral and systemic
      administration of three clinically used excitatory amino acid receptor
      antagonists (dextromethorphan, memantine, ketamine) on pain behaviors and edema
      produced by formalin (1.5% and 5%) in rats. Peripheral administration of
      dextromethorphan produced a locally mediated suppression of flinching behaviors
      induced by 1.5% and 5% formalin, but biting/licking behaviors were not affected.
      Memantine and ketamine had no effect on either of these behaviors. All three
      agents augmented edema produced by 1.5% and 5% formalin. When administered alone,
      dextromethorphan, memantine and ketamine produced an intrinsic paw swelling
      response, and this was blocked by the biogenic amine receptor antagonists
      mepyramine, phentolamine, methysergide and ketanserin. Following systemic
      administration, all three agents suppressed biting/licking behaviors, had no
      effect on flinching behaviors, and suppressed paw swelling induced by 5% formalin
      to varying degrees. These results provide evidence for a peripherally mediated
      antinociceptive action of dextromethorphan in the rat formalin test, but this may
      not necessarily be due to block of excitatory amino acid receptors as it is not
      observed with memantine or ketamine. All three agents produce a peripherally
      mediated paw swelling, which is likely due to blockade of biogenic amine
      reuptake. Systemic administration of all three agents produces antinociceptive
      and anti-inflammatory actions that may be due to block of excitatory amino acid
      receptors in the spinal cord.

PMID- 12206854
TI  - Naltrexone attenuates plasma nitric oxide release following acute heat stress.
AB  - Previous studies have shown that naltrexone attenuates morbidity and mortality in
      heat stress by inhibiting endogenous opioids. In this study, we hypothesized that
      naltrexone can decrease heat stress by attenuating nitric oxide release. Male
      Sprague-Dawley rats were pretreated with naltrexone or normal saline, and exposed
      to 45 degrees C for 25 min; controls were exposed to 25 degrees C. Colonic
      temperatures were recorded and plasma samples from an in-dwelling i.v. cannula
      were analyzed for nitrate/nitrite levels. Following heat stress, peak colonic
      temperature was significantly diminished (P < 0.05) in naltrexone-treated rats
      compared to saline-treated rats. Plasma nitrate/nitrite levels were significantly
      lower (P < 0.05) in naltrexone-treated rats compared to saline-treated rats.
      These findings suggest that naltrexone is able to attenuate the rise in plasma
      nitric oxide levels commonly observed after heat stress.

PMID- 12206855
TI  - Effect of the vasopressin receptor antagonist conivaptan in rats with heart
      failure following myocardial infarction.
AB  - Myocardial infarction often induces congestive heart failure accompanied by a
      significant increase in plasma vasopressin concentration. To delineate the role
      of vasopressin in the pathogenesis of congestive heart failure, the acute
      hemodynamic and aquaretic effects of conivaptan (YM087, 4'-(2-methyl-1,4,5,6
      tetrahydroimidazo[4,5-d][1]benzoazepine-6-carbonyl)-2-phenylbenzanilide
      monohydrochloride), a combined vasopressin V(1A) and V(2) receptor antagonist,
      were assessed in rats with heart failure induced by myocardial infarction. Left
      coronary artery ligation resulted in decreased left ventricular systolic pressure
      and first derivatives of left ventricular developed pressure, as well as
      increased left ventricular end-diastolic pressure, lung and right ventricular
      weight. Single oral administration of conivaptan (0.3 to 3.0 mg/kg) dose
      dependently increased urine volume and decreased urine osmolality in heart
      failure rats. Furthermore, conivaptan (3.0 mg/kg) attenuated the changes in left
      ventricular end-diastolic pressure, lung and right ventricular weight induced by
      heart failure while reducing blood pressure. These results show that vasopressin
      plays a significant role in elevating vascular tone through vasopressin V(1A)
      receptors and plays a major role in retaining free water through vasopressin V(2)
      receptors in this model of congestive heart failure. Additionally, conivaptan,
      with its dual vasopressin V(1A) and V(2) receptor-inhibiting properties, could
      exert a beneficial effect on cardiac function in the congestive heart failure rat
      model.

PMID- 12206856
TI  - Reperfusion duration paradox with late myocardial preconditioning in rabbits.
AB  - In this study, pharmacological late preconditioning was induced in 53 rabbits
      with an adenosine A(1) receptor agonist (2-chloro-N(6)-cyclopentyladenosine,
      CCPA, 100 microg/kg), or a NO-donor (S-nitroso-N-acetyl-penicillamine, SNAP, 2.5
      microg/kg/min; 75 min) vs. saline as control. Later, after 24 h, rabbits
      underwent a 30-min coronary occlusion and subsequent reperfusion. After 3 h of
      coronary artery reperfusion, infarct size was reduced with CCPA (43+/-4%) and
      SNAP (27+/-4%) vs. saline (56+/-4%). However, after 72 h of coronary artery
      reperfusion, infarct sizes were similar in all groups, demonstrating an only
      transient effect of late preconditioning against myocardial infarction. Combined
      administration of CCPA and SNAP failed to induce sustained cardioprotection.

PMID- 12206857
TI  - Renal protective effect of YM598, a selective endothelin ET(A) receptor
      antagonist, against diabetic nephropathy in OLETF rats.
AB  - We have investigated the effect of potassium (E)-N-[6-methoxy-5-(2
      methoxyphenoxy)-2-(pyrimidin-2-yl) pyrimidin-4-yl]-2-phenylenthenesulfonamidate
      (YM598), a selective endothelin ET(A) receptor antagonist, on renal function in
      Otsuka Long-Evans Tokushima Fatty (OLETF) rats, an animal model of type II
      diabetes. YM598 (0.1 or 1 mg kg(-1)), enalapril (5 mg kg(-1)), an angiotensin
      converting enzyme inhibitor, or vehicle was administered once daily by gastric
      gavage to 22-week-old male Otsuka Long-Evans Tokushima Fatty rats for 32 weeks.
      Enalapril but not YM598 mildly lowered blood pressure in the diabetic rats. YM598
      blunted the development of albuminuria in a dose-dependent manner. High dose of
      YM598 reduced albuminuria comparable to enalapril. Urinary endothelin-1 excretion
      was greater in the diabetic than in the control rats, and was not substantially
      influenced by the agents. These data suggest that endothelin is involved in the
      progression of diabetic nephropathy in Otsuka Long-Evans Tokushima Fatty rats,
      and an endothelin ET(A) receptor antagonist may be useful for the treatment of
      diabetic nephropathy.

PMID- 12206858
TI  - SCH 206272: a potent, orally active tachykinin NK(1), NK(2), and NK(3) receptor
      antagonist.
AB  - Experiments were performed to characterize the pharmacology of SCH 206272 [(R,R)
      1'[5-[(3,5-dichlorobenzoyl)methylamino]-3-(3,4-dichlorophenyl)-4(Z)
      (methoxyimino)pentyl]-N-methyl-2-oxo-[1,4'bipiperidine]-3-acetamide] as a potent
      and selective antagonist of tachykinin (NK) NK(1), NK(2), and NK(3) receptors.
      SCH 206272 inhibited binding at human tachykinin NK(1), NK(2), and NK(3)
      receptors (K(i) = 1.3, 0.4, and 0.3 nM, respectively) and antagonized [Ca(2+)](i)
      mobilization in Chinese hamster ovary (CHO) cells expressing the cloned human
      tachykinin NK(1), NK(2), or NK(3) receptors. SCH 206272 inhibited relaxation of
      the human pulmonary artery (pK(b) = 7.7 +/- 0.3) induced by the tachykinin NK(1)
      receptor agonist, [Met-O-Me] substance P and contraction of the human bronchus
      (pK(b = 8.2 +/- 0.3) induced by the tachykinin NK(2) receptor agonist, neurokinin
      A. In isolated guinea pig tissues, SCH 206272 inhibited substance P-induced
      enhancement of electrical field stimulated contractions of the vas deferens,
      (pK(b = 7.6 +/- 0.2), NKA-induced contraction of the bronchus (pK(b) = 7.7 +/-
      0.2), and senktide-induced contraction of the ileum. In vivo, oral SCH 206272
      (0.1-10 mg/kg, p.o.) inhibited substance P-induced airway microvascular leakage
      and neurokinin A-induced bronchospasm in the guinea pig. In a canine in vivo
      model, SCH 206272 (0.1-3 mg/kg, p.o.) inhibited NK(1) and NK(2) activities
      induced by exogenous substance P and neurokinin A. Furthermore, in guinea pig
      models involving endogenously released tachykinins, SCH 206272 inhibited
      hyperventilation-induced bronchospasm, capsaicin-induced cough, and airway
      microvascular leakage induced by nebulized hypertonic saline. These data
      demonstrate that SCH 206272 is a potent, orally active tachykinin NK(1), NK(2),
      and NK(3) receptor antagonist. This compound may have beneficial effects in
      diseases thought to be mediated by tachykinins, such as cough, asthma, and
      chronic obstructive pulmonary disease.

PMID- 12206859
TI  - Carbazochrome attenuates pulmonary dysfunction induced by a radiographic contrast
      medium in rats.
AB  - The effects of carbazochrome sodium sulfonate (AC-17), a capillary stabilizer, on
      pulmonary edema and dysfunction induced by ioxaglate, an ionic radiographic
      contrast medium, were evaluated in rats. The pulmonary edema was evaluated by the
      extravasation of intravenously injected Evans blue into lung tissues, while
      pulmonary dysfunction was determined by monitoring blood gasses including pO(2).
      Ioxaglate (4 g I/kg, i.v.) caused a marked increase in vascular permeability and
      a decrease in arterial pO(2). AC-17 reversed the ioxaglate-induced vascular
      hyperpermeability in a dose-dependent manner. In addition, AC-17 (10 mg/kg)
      significantly inhibited the decrease in arterial pO(2). In isolated rat pulmonary
      mast cells, ioxaglate markedly enhanced the histamine release, which was not
      affected by AC-17. On the other hand, AC-17 did significantly blocked the
      hyperpermeability induced in cultured bovine endothelial cells by tryptase,
      thrombin and proteinase-activated receptor-2 agonist peptide (SLIGKV-NH(2)).
      These findings suggest that AC-17 blocks radiographic contrast medium-induced
      pulmonary dysfunction by maintaining the endothelial barrier function. Thus, the
      compound is potentially useful for the prophylaxis of contrast media-induced
      acute pulmonary adverse events during angiography.

PMID- 12206860
TI  - Short-term prophylaxis with deoxyspergualin prevents testicular autoimmunity in
      mice.
AB  - The effects of the treatment with the immunosuppressant deoxyspergualin on the
      development of experimental autoimmune orchitis were studied. The results showed
      that C3H/He mice immunized with testicular germ cells and treated daily with
      either 0.3 or 3 mg/kg body weight deoxyspergualin during days 15-20 post
      immunization developed experimental autoimmune orchitis lesions with a
      significantly lower incidence and severity than did the control mice treated
      under the same experimental conditions with phosphate buffered saline (PBS). The
      effects of deoxyspergualin were clearly dose-dependent, and the higher dose of
      the drug also markedly reduced the degree of delayed type hypersensitivity
      responses against testicular germ cells. These data suggest that deoxyspergualin
      may be worthy of consideration for the prevention/treatment of human
      immunoinflammatory orchitis.

PMID- 12206861
TI  - Comparative evaluation of magnetization transfer MR imaging and in-vivo proton MR
      spectroscopy in brain tuberculomas.
AB  - We have compared and analyzed the value of in vivo proton MR spectroscopy (PMRS)
      and T1 weighted magnetization transfer (MT) MR imaging in tissue characterization
      of brain tuberculomas. We studied 33 cases of proven intracranial tuberculomas
      with in vivo PMRS and T1 weighted MT MR imaging. MT ratios from the rim and core
      of the tuberculomas were calculated and compared with metabolites seen on PMRS.
      Final diagnosis of tuberculoma was based on histopathology (n = 26) and/or
      associated tuberculous meningitis (n = 7) in all the cases. Out of the 33
      patients who underwent both PMRS and T1 weighted MT MR imaging, spectroscopy
      showed only lipids at 0.9 ppm, 1.3 ppm, 2.0 ppm, and 2.80 ppm in 26 cases while
      lipids at 0.9 ppm, 1.3 ppm, 2.0 ppm and 2.80 ppm along with choline at 3.22 ppm
      was seen in remaining 7 patients. MT ratios from the core or solid necrosis
      varied from 21-29% while from the rim or cellular region varied from 16-24%. MT
      ratios from all the 33 lesions were consistent with tuberculomas while PMRS
      showed choline along with lipids in 7 predominantly cellular lesions simulating a
      neoplasm. We conclude that T1 weighted MT MR imaging appears to be more
      consistent in the tissue characterization of brain tuberculomas.

PMID- 12206862
TI  - A longitudinal study of MR diffusion changes in normal appearing white matter of
      patients with early multiple sclerosis.
AB  - BACKGROUND AND PURPOSE: The stage at which normal appearing white matter (NAWM)
      abnormalities first appear in multiple sclerosis (MS) is not clear. The aim of
      our study was to monitor water diffusion changes over time in NAWM of patients
      with early MS. METHODS: Out of a consecutive series of patients enrolled in a MR
      study on clinically isolated syndrome (CIS), we selected 19 subjects who had
      completed a one year follow-up. The MR scans obtained at baseline and at 12
      months were reviewed according to the new criteria on the diagnosis of MS. Lesion
      load on T2 and T1 weighted images and the trace of the apparent diffusion
      coefficient in NAWM were measured both at baseline and at 12 months in patients
      and in 12 healthy controls. RESULTS: In three patients the diagnosis of MS was
      done at baseline based on MR. Thirteen patients developed MS during the study and
      in three patients the diagnosis remained "possible MS." TADC in NAWM in patients
      was significantly higher than in controls at the 12 months' follow-up but not at
      baseline (controls mean tADC +/- sd = 0.745 +/- 0.02 mm(2)/sec x 10(-3); patients
      mean tADC(12) +/- sd = 0.767 +/- 0.02 mm(2)/sec x 10(-3); p < 0.02). TADC and T2
      lesion load at 12 months were significantly correlated (p < 0.01). Patients
      exhibiting tADC(12) above a confidence interval had a significantly greater EDSS
      score at the same time period (EDSS(12) +/- sd = 1.9 +/- 0.5 and = 1.1 +/- 0.4
      respectively; p < 0.01). CONCLUSIONS: This study suggests that diffusion MR
      cannot detect alterations in NAWM of patients with a CIS suggestive of MS. After
      one year, when most patients develop MS, diffusion MR abnormalities in NAWM
      become apparent. These abnormalities are correlated with T2 lesion load and may
      contribute to neurological impairment.

PMID- 12206863
TI  - Magnetic resonance studies of laryngeal tumors implanted in nude mice: effect of
      treatment with bleomycin and electroporation.
AB  - Recently, a new type of cancer treatment has been introduced that combines pulsed
      electric fields (PEF) with anticancer drugs. The proposed mode of action is that
      PEF create transient pores in the membranes which allow entry of drugs into the
      cells. This method increases cytotoxicity of some anticancer drugs like bleomycin
      (BLM) by 2-3 orders of magnitude, which, in turn, reduces systemic drug dosage
      without decreasing efficacy. In the present study, magnetic resonance imaging
      (MRI) was used to determine changes in apparent water self-diffusion coefficients
      (ADC) and spin-lattice (T(1)) and spin-spin (T(2)) relaxation times that occur in
      an animal laryngeal tumor (HEp-2 cells) model with BLM delivered by PEF. A Bruker
      14 Tesla (600 MHz) wide-bore spectrometer with micro-imaging capability was used
      to generate all the data. Mice carrying approximately 8 mm tumors were treated
      with several combinations of drug and PEF. All measurements were made on tumor
      samples excised from mice 24 and 48 hours after treatment with (i) saline,
      intratumor injection (i.t.), (ii) BLM, i.t., (iii) saline with PEF, and (iv) BLM,
      i.t., followed by PEF. Although T(1) does not differ between the controls (i, ii,
      and iii) and full treatment (iv) 6.72 +/- 0.20 s vs. 6.31 +/- 1.7 s, T(2) for
      (iv) at 24 hours is significantly different from the controls 52.4 +/- 0.91 ms
      vs. 46.5 +/- 1.54 ms. T(2) differences between treatment and controls disappear
      at 48 hours. ADC increases significantly from 24 to 48 hours (7.31 +/- 0.16 x 10(
      6) to 8.28 +/- 0.28 x 10(-6) cm(2)/sec, p = 0.05). Longer T(2) values may reflect
      early apoptosis and tumor death when the tumor is structurally less dense. Higher
      ADC's, associated with the periphery of the tumors and the central region, may
      indicate loose structural organization and necrosis resulting from the
      combination treatment.

PMID- 12206864
TI  - Water diffusion features as indicators of muscle structure ex vivo.
AB  - The structures of two different bovine muscles, the Semitendinosus (ST) and the
      Triceps brachii (TB), were studied using quantitative maps obtained by diffusion
      tensor imaging at 4.7 T. The estimated features were: mean diffusivity, intra-
      and inter-voxel anisotropy and fiber tract orientation angles. Significant
      differences in anisotropy (fractional anisotropy and lattice index), spatial
      variations of anisotropy and fiber tract orientation were detected between ST and
      TB, and are discussed. Accumulation of free water, which diffuses more freely and
      isotropically than in the rest of the muscle, was detected and localized in ST.
      These results underline the usefulness of diffusion tensor measurements to
      characterize muscle structure and help understand the mechanisms of post mortem
      water exudation.

PMID- 12206865
TI  - MR imaging of fatigue stress injuries to bones: intra- and interobserver
      agreement.
AB  - The aim of this study was to determine the validity of MR imaging (MRI) in the
      assessment of stress-related injuries to bone.MR images of 50 military recruits
      (8 females and 42 males; 18-27 (mean 20) years of age) were retrospectively
      evaluated twice for stress injuries to bone by 4 radiologists (2 musculoskeletal
      radiologists, 2 radiology residents). Coronal T1-weighed (T1W) and STIR images,
      as well as axial and coronal T2-weighted (T2W) fat-suppressed images were taken
      using a 1.0T scanner. Rates for sensitivity, specificity, and accuracy of MRI of
      the stress-related injuries were calculated. Intraobserver and interobserver
      agreement was determined with kappa statistics. Rates for MRI sensitivity were 27
      96%, for specificity 65-100%, and for diagnostic accuracy 58-97%. Lowest rates
      were seen when reading T1W images and highest when reading STIR images. Readers
      showed moderate to excellent intraobserver agreement (kappa 0.75-0.95).
      Interobserver agreement was fair to excellent (kappa 0.41-0.91), and the lowest
      values were seen in the interpretation of T1W images. Normal findings could be
      differentiated from various grades of stress injury to bone.MRI is a valid means
      of revealing the presence of stress injuries to bone and their staging. Observer
      agreement is good to excellent when using T2W images and STIR images, while T1W
      images are of lesser value.

PMID- 12206866
TI  - An evaluation of gadolinium polyoxometalates as possible MRI contrast agent.
AB  - Two gadolinium polyoxometalates, K(9)GdW(10)O(36) and K(11)[Gd(PW(11)O(39))(2)],
      have been evaluated both in vivo and in vitro as candidates for tissue-specific
      MRI contrast agents. T(1)-relaxivities of 6.89 mM(-1). s(-1) for K(9)GdW(10)O(36)
      and 5.27 mM(-1). s(-1) for K(11)[Gd(PW(11)O(39))(2)] are slightly higher than
      that of the commercial MRI contrast agent (Gd-DTPA). Both compounds bind with
      bovine serum albumin and human serum transferrin and favorable liver-specific
      contrast enhancement in in vivo MRI with Sprague-Dawley rats after i.v.
      administration has been demonstrated. Imaging studies demonstrate that the two
      agents have a long residence time, showing MR signal enhancement in the liver for
      more than 40 min, longer than commercially available contrast agents. In vivo and
      in vitro assays showed that GdW(10) and Gd(PW(11))(2) are promising liver
      specific MRI contrast agents and GdW(10) may be used in the diagnosis of the
      pathological state. However, with the higher acute toxicity, the two gadolinium
      polyoxometalates need to be modified and studied further before clinical use.

PMID- 12206867
TI  - Numerical calculations of the static magnetic field in three-dimensional multi
      tissue models of the human head.
AB  - Susceptibility-induced perturbation of the static magnetic field by the human
      body during magnetic resonance imaging (MRI) leads to undesirable artifacts as
      well as valuable physiological information, as in functional MRI. The ability to
      calculate these perturbations for a multi-tissue human body model provides a
      powerful tool in designing hardware and acquisition methods for reducing the
      artifacts, and in relating observed image contrast to physiological origins. We
      have developed a method for calculating the static field in arbitrary 3D magnetic
      susceptibility distributions and performed calculations in a complete model of
      the human head and shoulders. The accuracy of our method was validated in regular
      geometries with known analytical solutions and in comparison with experimental
      results acquired from the head of the same human subject used for computer
      modeling. Results are presented in parts per million (ppm) deviation from the
      applied field strength and are valid for any imaging or spectroscopy system.

PMID- 12206868
TI  - Cerebellum segmentation employing texture properties and knowledge based image
      processing: applied to normal adult controls and patients.
AB  - A semi-automated method is described for segmenting the cerebellum from T(1)
      weighted 3-dimensional magnetic resonance imaging scans of adult controls and
      patients. The method relies on prior knowledge involving a user-defined template
      as a guide to aid the segmentation of the cerebellum. As the gray and white
      matter intensity distribution in the cerebellum has a complex pattern, texture
      information that identified the "graininess" was employed to capture the
      intensity distribution of voxels. The textural information was used to group
      voxels in a small circular structuring element as belonging to the cerebellum
      region. The cerebella from scans of 15 of the 20 subjects were segmented both
      manually and using the semi-automated procedure; the results were strongly
      correlated (r = 0.985, n = 15, p < 0.0001), and the volumes obtained from the two
      methods differed by 2.3%. The cerebellar volumes in 10 normal subjects and 10 age
      and sex-matched patients with a neuropsychiatric disorder (schizophrenia) did
      not differ significantly (p = 0.18). The whole cerebellum was segmented in
      approximately 30 min using the semi-automated procedure. The method described is
      robust, easy-to-use, fairly fast and gives objective measurements.

PMID- 12206869
TI  - Graded image segmentation of brain tissue in the presence of inhomogeneous radio
      frequency fields.
AB  - Image segmentation is used increasingly to interpret MR spectroscopic data of the
      brain, using image contrast to identify gray matter (GM), white matter (WM), and
      cerebral spinal fluid (CSF). T(1)- or T(2)-weighted images are typically used,
      but poor shimming, susceptibility effects, and small variations in B(1) and
      receptivity cause difficulties in tissue identification. Quantitative imaging of
      T(1) can reduce many of these difficulties but is still subject to complications
      when B(1) has large variations like those observed with the surface coils often
      used for spectroscopy. In this study, B(1) imaging was implemented to support
      quantitative imaging of T(1) with either a surface coil or a volume coil. The
      T(1) observed by this method is a continuous function across mixtures of WM/GM
      and GM/CSF, and this function was measured and used to convert the images of T(1)
      to maps of percent GM, WM, and CSF.

PMID- 12206870
TI  - MRI inter-slice reconstruction using super-resolution.
AB  - MRI reconstruction using super-resolution is presented and shown to improve
      spatial resolution in cases when spatially-selective RF pulses are used for
      localization. In 2-D multislice MRI, the resolution in the slice direction is
      often lower than the in-plane resolution. For certain diagnostic imaging
      applications, isotropic resolution is necessary but true 3-D acquisition methods
      are not practical. In this case, if the imaging volume is acquired two or more
      times, with small spatial shifts between acquisitions, combination of the data
      sets using an iterative super-resolution algorithm gives improved resolution and
      better edge definition in the slice-select direction. Resolution augmentation in
      MRI is important for visualization and early diagnosis. The method also improves
      the signal-to-noise efficiency of the data acquisition.

PMID- 12206871
TI  - Comparing mRNA levels of genes encoding leptin, leptin receptor, and lipoprotein
      lipase between dairy and beef cattle.
AB  - Body weight and fat mass vary distinctly between German Holstein (dairy cattle)
      and Charolais (beef cattle). The aim of this study was to determine whether the
      expression of the obese (Ob) gene and lipoprotein lipase (LPL) gene in fat
      tissues and expression of the long isoform leptin receptor (Ob-Rb) gene in the
      hypothalamus were different between these two cattle breeds. Body weight and the
      area of longissimus muscle cross-section of German Holstein were lower (P<0.001),
      while body fat content, as well as the omental and perirenal fat mass were higher
      (P<0.001), compared to Charolais. Plasma insulin and leptin levels between two
      cattle breeds were determined by radioimmunoassay. Compared to Charolais, plasma
      insulin concentrations were significantly higher (P<0.01), and plasma leptin
      levels were tended to be higher (P<0.1) in German Holstein. Ob mRNA levels in
      subcutaneous and perirenal fat depots, but not in the omental fat depot, were
      significantly higher (P<0.05) in German Holstein than in Charolais. LPL mRNA
      expression in the perirenal fat depot of German Holstein was greater in abundance
      than that of Charolais. No significantly different LPL mRNA levels were found in
      subcutaneous and omental fat depots, and Ob-Rb mRNA levels in the hypothalamus
      between these two cattle breeds (P<0.05). Both Ob and LPL expression was greater
      in perirenal and omental fat depots than in the subcutaneous fat depot (P<0.05).
      Data indicated that in bovine the Ob and LPL gene expression levels in perirenal
      fats are an important index that is associated with body fat content, while Ob-Rb
      in hypothalamus is not.

PMID- 12206872
TI  - Regulation of endometrial granulocyte macrophage-colony stimulating factor (GM
      CSF) in the ewe.
AB  - Granulocyte macrophage-colony stimulating factor (GM-CSF) increases ovine
      interferon-tau (oIFNtau) secretion by ovine conceptuses, but endometrial
      production of GM-CSF has not been characterized. Endometrial GM-CSF expression
      was evaluated in ovariectomized ewes implanted with estradiol-17beta (E(2))
      and/or progesterone (P(4)) for 14 days, in day 14 cyclic and day 14 pregnant
      ewes. Relative levels of endometrial GM-CSF mRNA were 3-fold higher in E(2)- and
      E(2)/P(4)-treated ewes than that of control or P(4)-treated ovariectomized ewes.
      Levels of endometrial GM-CSF mRNA for cyclic ewes were similar to E(2)- and
      E(2)/P(4)-treated ewes, but amounts of GM-CSF mRNA in pregnant ewes were 2-fold
      higher. GM-CSF concentrations in endometrial culture media, determined by GM-CSF
      bioassay, for cyclic and E(2)/P(4)-treated ovariectomized ewes were 3-fold higher
      than those of control, E(2)- and P(4)-treated ovariectomized ewes; however,
      amounts of GM-CSF in pregnant ewes were 2-fold higher. Immunoreactive GM-CSF,
      examined by western blot, was detected in the culture medium from E(2)/P(4)
      treated ovariectomized, cyclic and pregnant ewes. Luminal and glandular epithelia
      and stromal regions were determined to be sites of GM-CSF expression by
      immunohistochemistry and in situ hybridization techniques. Data indicate that
      combined E(2) and P(4) treatment of ovariectomized ewes is sufficient to restore
      GM-CSF expression to the level found in cyclic ewes; however, GM-CSF mRNA and
      protein in pregnant ewes is 2-fold greater than in ovariectomized or cyclic ewes.
      These data suggest that the conceptus, in addition to steroids, may play a role
      in the regulation of endometrial production of GM-CSF.

PMID- 12206873
TI  - Molecular cloning and tissue distribution of the ovine somatostatin receptor
      subtype 5: osst5.
AB  - The sheep is a valuable model to study growth hormone (GH) neuroregulation since
      its GH secretion pattern is close to that in humans and an integrated
      physiological approach is possible in this species. Somatostatin receptor subtype
      5 (sst5) appears to be important in GH regulation but the ovine sst5 gene (osst5)
      has not yet been cloned. We report here the cloning of sst5 in that species. We
      screened a cDNA sheep library and isolated a 1.24 kb cDNA, which includes the
      whole coding region of osst5. The predicted protein consists of 367 amino acids
      exhibiting a putative seven transmembrane domain topology typical of G protein
      coupled receptors. Nucleotide sequence comparisons with that of other species
      sst5 showed that osst5 displays 83.8, 81 and 79.7% homology with human, rat, and
      mice sst5, respectively. Southern blot analysis of ovine cortex DNA demonstrated
      that osst5 is encoded by a single gene. Osst5 transiently expressed in Chinese
      Hamster ovary (CHO) cells exhibit a high affinity for somatostatin-14. Reverse
      transcriptase-polymerase chain reaction (RT-PCR) studies demonstrated that osst5
      mRNAs are present in pituitary, cortex, hypothalamus, hippocampus, colon and
      adrenal gland. The cloning of osst5 should provide a useful tool to study the
      mechanisms through which somatostatin inhibits hormone secretion in the sheep.

PMID- 12206874
TI  - Characterization of leptin binding in bovine kidney membranes.
AB  - The interactions of leptin with its receptor and other leptin binding sites is
      not well described or understood. We have used Scatchard analysis of saturation
      binding data to characterize the affinity of leptin for binding sites in bovine
      kidney membranes. 125I-Leptin was used in saturation studies, over a range of
      concentrations from 50 pM to 9 nM. 125I-Leptin differentiated a high affinity
      binding site from an abundant low affinity site. The high affinity/low density
      binding site (putative leptin receptor) had K(d)=0.098 nM and B(max)=46.2f mol/mg
      protein. An additional class of low affinity, highly abundant sites with an
      apparent K(d)=175 nM, and B(max)=574 fmol/mg protein was characterized. The
      association and dissociation kinetics for 125I-leptin binding were also studied.
      Dissociation of the leptin-receptor complex was very rapid, and this necessitated
      the use of a specially developed separation method for radioligand binding
      studies (precipitation with PEG and filtration). Competitive displacement of 125I
      leptin by mouse and human leptin and polyclonal anti-bovine leptin antibodies was
      dose-dependent. Specificity of binding was shown as bound 125I-leptin was not
      displaced by insulin or control antibodies. These data indicate that leptin binds
      the bovine leptin receptor with high affinity and that a pool of leptin is bound
      to abundant cell membrane-associated proteins. These observations are consistent
      with the plasma concentration range for leptin and imply that free leptin
      concentration in the tissues may be partially buffered by cell-associated and
      bound forms in plasma. Thus, acute changes in leptin secretion may have little
      effect at the leptin receptor. The development of leptin agonists/antagonists
      should facilitate further characterization of leptin binding and clarify the role
      of abundant low affinity binding sites at the leptin axis.

PMID- 12206875
TI  - Regulation of haptoglobin secretion by recombinant bovine cytokines in primary
      cultured bovine hepatocytes.
AB  - We examined the regulation of haptoglobin (Hp) secretion in primary cultured
      bovine hepatocytes using recombinant bovine (rb) proinflammatory cytokines. The
      concentrations of Hp in the supernatant of cultured hepatocytes after incubation
      with rb interleukin (IL)-6, rb tumor necrosis factor (TNF)-alpha, rbIL-1 beta or
      rbIFN-gamma alone or with combinations of two of these cytokines were measured by
      ELISA. The rbIL-6, rbTNF-alpha and rbIL-1 beta increased Hp synthesis, but rbIFN
      gamma did not, and rbIL-6 was the most effective Hp inducer among these
      cytokines. The Hp secretion was accelerated synergistically by combined treatment
      with rbIL-6 and rbTNF-alpha, whereas it remained unchanged with a combination of
      rbIL-6 and rbIL-1 beta. In contrast, the combination of rbIL-6 and rbIFN-gamma
      downregulated Hp secretion. In conclusion, IL-6 is the principal cytokine in Hp
      secretion in bovine hepatocytes in vitro, and its activity may be regulated by
      other cytokines.

PMID- 12206876
TI  - Oxytocin stimulates secretion of prostaglandin F(2alpha) from endometrial cells
      of swine in the presence of progesterone.
AB  - Oxytocin (OT) stimulates endometrial secretion of prostaglandin (PG) F(2 alpha)
      during corpus luteum regression in swine but there is differential responsiveness
      to OT among endometrial cell types. To determine if progesterone influenced
      responsiveness of luminal epithelial, glandular epithelial, and stromal cells to
      100 nM OT during luteolysis in swine, cells were isolated from endometrium of 15
      gilts by differential enzymatic digestion and sieve filtration on day 16
      postestrus and cultured continuously in the presence of 0, 10 or 100 nM
      progesterone. For phospholipase C (PLC) activity and PGF(2 alpha) secretion,
      stromal cells were most responsive to OT (P<0.01) in the absence of progesterone,
      whereas luminal epithelial cells were unresponsive and glandular epithelial cells
      displayed an intermediate response to OT (P<0.09). Progesterone enhanced PLC
      activity linearly in glandular epithelial cells (P<0.05) and influenced it
      quadratically in stromal cells (P=0.05). The effect of OT and progesterone on PLC
      activity in luminal epithelial cells was not significant, and progesterone did
      not increase PLC activity in response to OT in any cell type. Culture in the
      presence of progesterone, enhanced PGF(2 alpha) secretion in response to OT in
      luminal epithelial cells (P<0.05) but not in glandular epithelial or stromal
      cells. Progesterone also increased overall PGF(2 alpha) release from glandular
      epithelial (P<0.05) and stromal cells (P<0.06) across both levels of OT
      treatment. These results indicate that progesterone enhanced PGF(2 alpha)
      secretion from luminal epithelial cells in response to OT and increased basal
      PGF(2 alpha) release from glandular epithelial and stromal cells.

PMID- 12206877
TI  - Hepatitis B treatment: rational combination chemotherapy based on viral kinetic
      and animal model studies.
AB  - Hepatitis B virus (HBV) causes a generally non-cytopathic infection in the liver.
      Even though HBV is a DNA virus, it replicates via reverse transcription which is
      coordinated within the viral nucleocapsid by the virus-specific polymerase. The
      major transcriptional template is the viral mimichromosome from which the viral
      DNA exists as a covalently closed circular (ccc) molcule. The virus infects
      hepatocytes but can also be found in non-hepatocyte reservoirs such as bile-duct
      epithelium, mesangial cells of the kidney, pancreatic islet cells and lymphoid
      cells. When patients infected with HBV are treated with either interferon alpha
      or lamivudine, responses are variable and unpredictable. Sophisticated
      mathematical models analysing the dynamics of viral clearance during antiviral
      therapy have recently been applied to chronic hepatitis B. Typically complex
      profiles, rather than the usual biphasic responses seen with other diseases have
      been observed, indicating that antiviral efficacy requires substantila
      improvement. This may be achieved with combination chemotherapy. However, chronic
      hepatitis B is a complex and heterogeneous disease entity, and the challenge for
      the future is to define measurable end-points of treatment and address key
      virological issues such as the role of cccDNA and extra-hepatocyte replication in
      treatment failure. Clearly, new therapies and effective combination therapy
      protocols are urgently required in order to improve the present poor response
      rates in patients undergoing treatment.

PMID- 12206878
TI  - Nucleotide triphosphatase/helicase of hepatitis C virus as a target for antiviral
      therapy.
AB  - The RNA nucleoside triphosphatase (NTPase)/helicases represent a large family of
      proteins that are detected in almost all biological systems where RNA plays a
      central role. The enzymes are capable of enzymatically unwinding duplex RNA
      structures by disrupting the hydrogen bonds that keep the two strands together.
      The strand separating activity is associated with hydrolysis of nucleoside
      triphosphate (NTP). Because of this, potential specific inhibitors of
      NTPase/helicases could act by one or more of the following mechanisms: (i)
      inhibition of NTPase activity by interference with NTP binding, (ii) inhibition
      of NTPase activity by an allosteric mechanism and (iii) inhibition of the
      coupling of NTP hydrolysis at the unwinding reaction. There are also other
      inhibitory mechanisms conceivable, which may involve a modulation of the
      interaction of the enzyme with its RNA substrate, for example, (iv) the
      competitive inhibition of RNA binding and (v) the inhibition of the unwinding by
      sterical blockade of the translocation of the NTPase/helicase along the
      polynucleotide chain. NTPase/helicase has also been identified in the viral
      genome of hepatitis C virus (HCV) which is a member of the Flaviviridae family.
      It is conceivable that the inhibition of the unwinding activity of the enzyme
      leads to the inhibition of virus replication and this may represent a novel
      antiviral strategy. This review updates the current spectrum of inhibitors
      targeting different mechanisms by which the NTPase and/or helicase activities of
      the HCV NTPase/helicase are inhibited. Consequently, some of the compounds might
      be important as antiviral agents against HCV.

PMID- 12206879
TI  - 2-Chloro-3-pyridin-3-yl-5,6,7,8-tetrahydroindolizine-1-carboxamide (CMV423), a
      new lead compound for the treatment of human cytomegalovirus infections.
AB  - Human cytomegalovirus (HCMV) remains one of the major pathogens in
      immunocompromised patients (AIDS and transplants) and the main cause for
      congenital infections leading from slight cognitive defects up to severe mental
      retardation. The drugs that are currently available for the treatment of HCMV
      infections, i.e. ganciclovir, foscarnet and cidofovir, are all acting at the
      level of the viral DNA polymerase. Here we describe an entirely new molecule, the
      2-chloro-3-pyridin-3-yl-5,6,7,8-tetrahydroindolizine-1-carboxamide (CMV423), that
      shows very potent in vitro activity against HCMV. CMV423 is highly active against
      HCMV reference strains and clinical isolates, but also against those strains,
      isolated from patients or emerging after in vitro selection, that are resistant
      to either ganciclovir, foscarnet or cidofovir. CMV423 also showed activity in two
      ex vivo models, that are both highly relevant for the pathophysiology of HCMV,
      the retinal pigment epithelial and the bone marrow stromal cell assays. Viral
      antigen expression analysis by flow cytometry, as well as time of addition
      experiments, confirmed that CMV423 acts on a step of the viral replicative cycle
      that precedes the DNA polymerase step and, most likely, coincides with the
      immediate early (IE) antigen synthesis. Finally, CMV423 combined with either
      ganciclovir, foscarnet or cidofovir in checkerboard experiments demonstrated a
      highly synergistic activity.

PMID- 12206881
TI  - Mode of inactivation of arenaviruses by disulfide-based compounds.
AB  - Several disulfide-based compounds, including intermolecular aromatic disulfides
      of the type Ph-S-S-Ph and dithianes with the sulfur atoms tethered in a ring
      structure, have shown effective inhibitory activity against the arenaviruses
      Junin (JUNV), agent of Argentine hemorrhagic fever, and Tacaribe (TCRV). These
      compounds showed a strong virucidal effect with inactivating concentration 50%
      (IC(50)) values in the range 0.6-5.0 microM, and also were effective to reduce
      virus yields from infected cells. The mode of inactivating action of two active
      compounds, the aromatic bis disulfide NSC20625 and the dithiane NSC624152, was
      further studied. Both compounds were able to inactivate arenaviruses after a few
      minutes of direct contact with virions, in a concentration- and time-dependent
      manner. The ability of drug-treated virus to perform several steps of the
      replication cycle was analyzed. The killed virus particles were found to bind and
      enter to Vero cells with the same efficacy as infectious native virions, but the
      ability of inactivated virions to synthesize viral proteins in Vero cells was
      abolished. Thus, treatment of JUNV and TCRV with these compounds destroyed virion
      infectivity, generating particles which entered the host cell but were unable to
      complete the viral biosynthetic processes.

PMID- 12206880
TI  - The combination of interferon alpha-2b and n-butyl deoxynojirimycin has a greater
      than additive antiviral effect upon production of infectious bovine viral
      diarrhea virus (BVDV) in vitro: implications for hepatitis C virus (HCV) therapy.
AB  - Interferon alpha-2b (IFN) alone or in combination with Ribavirin is approved in
      the United States for the treatment of chronic hepatitis C virus (HCV) infection.
      We have previously reported that the glucosidase inhibitor, n-butyl
      deoxynojirimycin (nB-DNJ) inhibits the production of infectious bovine diarrhea
      virus (BVDV) (Proc. Natl. Acad. Sci. 96 (1999) 11878). Since BVDV has been used
      as a model for HCV and grows productively in tissue culture, and IFN and
      glucosidase inhibitors are thought to act at different steps in the virus life
      cycle, it was of interest to determine the antiviral impact of combining nB-DNJ
      with IFN. Using plaque reduction and single-step growth analyses of the
      cytopathic BVDV strain NADL, data are presented that shows human IFN inhibited
      BVDV production in a dose dependent manner, with 3 IU/ml inhibiting 50% of the
      yield of virus (IC50) when added within 1 h post infection. Under the same
      conditions, the glucosidase inhibitors nB-DNJ and castanospermine (CST) also
      prevented BVDV production in a dose dependent manner with IC50s of 226 microM and
      47 microM, respectively. In combination with 138 microM nB-DNJ the apparent IC50
      for IFN was 0.056 IU/ml. This 54-fold increase in IFN potency suggests that nB
      DNJ can synergize with IFN. Two additional independent analyses were performed to
      measure combination effects which demonstrated that the combined antiviral effect
      of nB-DNJ and IFN were greater than would be expected for a simple additivity.
      These data are consistent with an interpretation that glucosidase inhibitors and
      IFN have a synergistic antiviral effect in tissue culture. The relevance of these
      finding to treatment of HCV infection is discussed.

PMID- 12206882
TI  - Antiherpes simplex virus type 2 activity of casuarinin from the bark of
      Terminalia arjuna Linn.
AB  - Casuarinin, a hydrolyzable tannin isolated from the bark of Terminalia arjuna
      Linn. (Combretaceae), was investigated for its antiviral activity on herpes
      simplex type 2 (HSV-2) in vitro. Results showed that the IC(50) of casuarinin in
      XTT and plaque reduction assays were 3.6+/-0.9 and 1.5+/-0.2 microM,
      respectively. The 50% cytotoxic concentration for cell growth (CC(50)) was 89+/-1
      microM. Thus, the selectivity index (SI) (ratio of CC(50) to IC(50)) of
      casuarinin was 25 and 59 for XTT and plaque reduction assays, respectively.
      Casuarinin continued to exhibit antiviral activity even added 12 h after
      infection. During the attachment assay, casuarinin was shown to prevent the
      attachment of HSV-2 to cells. Furthermore, casuarinin also exhibited an activity
      in inhibiting the viral penetration. Interestingly, casuarinin was virucidal at a
      concentration of 25 microM, reducing viral titers up to 100,000-fold. This study
      concludes that casuarinin possesses anti-herpesvirus activity in inhibiting viral
      attachment and penetration, and also disturbing the late event(s) of infection.

PMID- 12206883
TI  - Multidrug transporters and antibiotic resistance in Lactococcus lactis.
AB  - The Gram-positive bacterium Lactococcus lactis produces two distinct multidrug
      transporters, designated LmrA and LmrP, that both confer resistance to a wide
      variety of cationic lipophilic cytotoxic compounds as well as to many clinically
      relevant antibiotics. While LmrP is a proton/drug antiporter that belongs to the
      major facilitator superfamily of secondary transporters, LmrA is an ATP-dependent
      primary transporter that belongs to the ATP-binding cassette superfamily of
      transport proteins. Both LmrA and LmrP function as "hydrophobic vacuum cleaners"
      by excreting lipophilic cationic compounds from the inner leaflet of the membrane
      directly into the external water phase. LmrA is both functionally and
      structurally homologous to the human multidrug transporter P-glycoprotein. LmrA
      is a half ABC transporter that is functional as a homodimer, consistent with the
      general four-domain organization of ABC transporters, and is proposed to mediate
      drug transport by an alternating two-site transport mechanism.

PMID- 12206884
TI  - A conformational change in the isolated NADP(H)-binding component (dIII) of
      transhydrogenase induced by low pH: a reflection of events during proton
      translocation by the complete enzyme?
AB  - Transhydrogenase couples the reduction of NADP(+) by NADH to inward proton
      translocation across the bacterial (or mitochondrial) membrane. Conformational
      changes in the NADP(H)-binding component of the enzyme (dIII) are central to the
      coupling mechanism. In the "open" state, NADP(H) bound to dIII can readily
      exchange with nucleotides in the solvent but hydride transfer [to/from NAD(H)
      bound to dI] is prevented. In the "occluded" state, bound NADP(H) cannot exchange
      with solvent nucleotides but the hydride transfer reaction is permitted. It was
      previously found that the conformational state of isolated, recombinant dIII is
      pH dependent. At neutral pH, the protein adopts a conformation resembling the
      occluded state, and at low pH, it adopts a conformation resembling the open
      state. The crystal structure of dIII indicates that the loop E "lid" might be
      largely responsible for the very high affinity of the protein for NADP(H). In
      this paper we show, using fluorescence resonance energy transfer, that the
      distance between the apex of loop E of isolated dIII, and the core of the
      protein, increases when the solution pH is lowered. This is consistent with the
      view that the lid is retracted to permit NADPH release during turnover of the
      complete enzyme.

PMID- 12206885
TI  - Mitochondrial bound type II hexokinase: a key player in the growth and survival
      of many cancers and an ideal prospect for therapeutic intervention.
AB  - Despite more than 75 years of research by some of the greatest scientists in the
      world to conquer cancer, the clear winner is still cancer. This is reflected
      particularly by liver cancer that worldwide ranks fourth in terms of mortality
      with survival rates of no more than 3-5%. Significantly, one of the earliest
      discovered hallmarks of cancer had its roots in Bioenergetics as many tumors were
      found in the 1920s to exhibit a high glycolytic phenotype. Although research
      directed at unraveling the underlying basis and significance of this phenotype
      comprised the focus of cancer research for almost 50 years, these efforts
      declined greatly from 1970 to 1990 as research into the molecular and cell
      biology of this disease gained center stage. Certainly, this change was necessary
      as the new knowledge obtained about oncogenes, gene regulation, and programmed
      cell death once again placed Bioenergetics in the limelight of cancer research.
      Thus, we now have a much better molecular understanding of the high glycolytic
      phenotype of many cancers, the pivotal roles that Type II hexokinase
      mitochondrial interactions play in this process to promote tumor cell growth and
      survival, and how this new knowledge can lead to improved therapies that may
      ultimately turn the tide on our losing war on cancer.

PMID- 12206886
TI  - Electron transfer between yeast cytochrome bc(1) complex and cytochrome c: a
      structural analysis.
AB  - The structure of the complex between cytochrome c (CYC) and the cytochrome bc(1)
      complex (QCR) from yeast crystallized with an antibody fragment has been recently
      determined at 2.97 A resolution [Proc. Natl. Acad. Sci. U. S. A. 99 (2002) 2800].
      CYC binds to subunit cytochrome c(1) of the enzyme stabilized by hydrophobic
      interactions surrounding the heme crevices creating a small, compact contact
      site. A central cation-pi interaction is an important and conserved feature of
      CYC binding. Peripheral patches with highly conserved complementary charges
      further stabilize the enzyme-substrate complex by long-range electrostatic forces
      and may affect the orientation of the substrate. Size and characteristics of the
      contact site are optimal for a transient electron transfer complex. Kinetic data
      show a bell-shaped ionic strength dependence of the cytochrome c reduction with a
      maximum activity near physiological ionic strength. The dependence is less
      pronounced in yeast compared to horse heart CYC indicating less impact of
      electrostatic interactions in the yeast system. Interestingly, a local QCR
      activity minimum is found for both substrates at 120-140 mM ionic strength. The
      architecture of the complex results in close distance of both c-type heme groups
      allowing the rapid reduction of cytochrome c by QCR via direct heme-to-heme
      electron transfer. Remarkably, CYC binds only to one of the two possible binding
      sites of the homodimeric complex and binding appears to be coordinated with the
      presence of ubiquinone at the Q(i) site. Regulatory aspects of CYC reduction are
      discussed.

PMID- 12206887
TI  - Coupling proton movements to c-ring rotation in F(1)F(o) ATP synthase: aqueous
      access channels and helix rotations at the a-c interface.
AB  - F(1)F(o) ATP synthases generate ATP by a rotary catalytic mechanism in which H(+)
      transport is coupled to rotation of a ring of c subunits within the transmembrane
      sector of the enzyme. Protons bind to and then are released from the aspartyl-61
      residue of subunit c at the center of the membrane. Proton access channels to and
      from aspartyl-61 are thought to form in subunit a of the F(o) sector. Here, we
      summarize new information on the structural organization of subunit a and the
      mapping of aqueous accessible residues in the fourth and fifth transmembrane
      helices (TMHs). Cysteine substituted residues, lying on opposite faces of aTMH-4,
      preferentially react with either N-ethyl-maleimide (NEM) or Ag(+). We propose
      that aTMH-4 rotates to alternately expose each helical face to aspartyl-61 of
      subunit c during the proton transport cycle. The concerted helical rotation of
      aTMH-4 and cTMH-2 are proposed to be coupled to the stepwise mechanical movement
      of the c-rotor.

PMID- 12206888
TI  - The bc(1) complex of the iron-grown acidophilic chemolithotrophic bacterium
      Acidithiobacillus ferrooxidans functions in the reverse but not in the forward
      direction. Is there a second bc(1) complex?
AB  - Acidithiobacillus ferrooxidans is an acidophilic chemolithotrophic bacterium that
      can grow in the presence of either a weak reductant, Fe(2+), or reducing sulfur
      compounds that provide more energy for growth than Fe(2+). Here we first review
      the latest findings about the uphill electron transfer pathway established in
      iron-grown A. ferrooxidans, which has been found to involve a bc(1) complex. We
      then provide evidence that this bc(1) complex cannot function in the forward
      direction (exergonic reaction), even with an appropriate substrate. A search for
      the sequence of the three redox subunits of the A. ferrooxidans bc(1) complex
      (strain ATCC 19859) in the complete genome sequence of the A. ferrooxidans ATCC
      23270 strain showed the existence of two different bc(1) complexes in A.
      ferrooxidans. Cytochrome b and Rieske protein sequence comparisons allowed us to
      point out some sequence particularities of these proteins in A. ferrooxidans.
      Lastly, we discuss the possible reasons for the existence of two different
      "classical" bc(1) complexes and put forward some suggestions as to what role
      these putative complexes may play in this acidophilic chemolithotrophic
      bacterium.

PMID- 12206889
TI  - Peroxisomes: surprisingly versatile organelles.
AB  - Peroxisome development is a dynamic process that is not yet completely
      understood. We use the methylotrophic yeast Hansenula polymorpha as model in our
      studies on peroxisome homeostasis. Cells of this species may contain different
      types of peroxisomes that differ in protein composition and capacity to
      incorporate matrix proteins. This protein import machinery is highly flexible and
      can accommodate unfolded and complex folded proteins.

PMID- 12206891
TI  - Detection and interpretation of redox potential optima in the catalytic activity
      of enzymes.
AB  - It is no surprise that the catalytic activity of electron-transport enzymes may
      be optimised at certain electrochemical potentials in ways that are analogous to
      observations of pH-rate optima. This property is observed clearly in experiments
      in which an enzyme is adsorbed on an electrode surface which can supply or
      receive electrons rapidly and in a highly controlled manner. In such a way, the
      rate of catalysis can be measured accurately as a function of the potential
      (driving force) that is applied. In this paper, we draw attention to a few
      examples in which this property has been observed in enzymes that are associated
      with membrane-bound respiratory chains, and we discuss its possible origins and
      implications for in vivo regulation.

PMID- 12206890
TI  - Interactions of quinone with the iron-sulfur protein of the bc(1) complex: is the
      mechanism spring-loaded?
AB  - Since available structures of native bc(1) complexes show a vacant Q(o)-site,
      occupancy by substrate and product must be investigated by kinetic and
      spectroscopic approaches. In this brief review, we discuss recent advances using
      these approaches that throw new light on the mechanism. The rate-limiting
      reaction is the first electron transfer after formation of the enzyme-substrate
      complex at the Q(o)-site. This is formed by binding of both ubiquinol (QH(2)) and
      the dissociated oxidized iron-sulfur protein (ISP(ox)). A binding constant of
      approximately 14 can be estimated from the displacement of E(m) or pK for quinone
      or ISP(ox), respectively. The binding likely involves a hydrogen bond, through
      which a proton-coupled electron transfer occurs. An enzyme-product complex is
      also formed at the Q(o)-site, in which ubiquinone (Q) hydrogen bonds with the
      reduced ISP (ISPH). The complex has been characterized in ESEEM experiments,
      which detect a histidine ligand, likely His-161 of ISP (in mitochondrial
      numbering), with a configuration similar to that in the complex of ISPH with
      stigmatellin. This special configuration is lost on binding of myxothiazol.
      Formation of the H-bond has been explored through the redox dependence of
      cytochrome c oxidation. We confirm previous reports of a decrease in E(m) of ISP
      on addition of myxothiazol, and show that this change can be detected
      kinetically. We suggest that the myxothiazol-induced change reflects loss of the
      interaction of ISPH with Q, and that the change in E(m) reflects a binding
      constant of approximately 4. We discuss previous data in the light of this new
      hypothesis, and suggest that the native structure might involve a less than
      optimal configuration that lowers the binding energy of complexes formed at the
      Q(o)-site so as to favor dissociation. We also discuss recent results from
      studies of the bypass reactions at the site, which lead to superoxide (SO)
      production under aerobic conditions, and provide additional information about
      intermediate states.

PMID- 12206892
TI  - Supramolecular organisation of the photosynthetic chain in anoxygenic bacteria.
AB  - This minireview summarizes our present view of the supramolecular organization of
      the photosynthetic apparatus of Rhodobacter sphaeroides and Rhodobacter
      capsulatus. These two species present a close association between two reaction
      centers (RCs), one cytochrome (cyt) bc(1) and one cyt c. In R. sphaeroides, the
      RCs are only partially surrounded by LH1 complexes. This open ring of LH1
      complexes is required for an efficient photoinduced cyclic electron transfer only
      under conditions where the quinone pool totally reduced. When the quinone pool is
      partially oxidized, a closed ring of LH1 complexes around the RCs does not impair
      the exchange of quinone molecules between the RC and the cyt bc(1) complex. To
      explain the efficient photochemistry of the various species which possess a RC
      surrounded by a closed ring of LH, it is proposed that their quinone pool is
      partially oxidized even under anaerobic condition.

PMID- 12206893
TI  - Inter- and intra-molecular electron transfer in the cytochrome bc(1) complex.
AB  - In this review, we compare the intra-molecular and inter-molecular electron
      transfer rate constants of the high-potential branch of the cytochrome bc(1)
      complex. Several methods such as the conventional stopped-flow spectroscopy, pH
      induced electron transfer, photoactivated ruthenium complex induced electron
      transfer and photoreleaseable caged quinol, have been used to determine reaction
      rates between redox centers in an attempt to elucidate the reaction mechanism of
      this vital energy conserving complex. Since the most active pure cytochrome bc(1)
      complex has a turnover number of 800 s(-1), any step with a rate constant much
      larger than this will not be rate-limiting. The most likely rate-limiting step is
      the cytochrome b redox state governed movement of the head domain of iron-sulfur
      protein from its electron-accepting site ("fixed" or "b-state" position) to its
      electron donating site ("c(1)-state" position).

PMID- 12206894
TI  - Structure, subunit function and regulation of the coated vesicle and yeast
      vacuolar (H(+))-ATPases.
AB  - The vacuolar (H(+))-ATPases (or V-ATPases) are ATP-dependent proton pumps that
      function to acidify intracellular compartments in eukaryotic cells. This
      acidification is essential for such processes as receptor-mediated endocytosis,
      intracellular targeting of lysosomal enzymes, protein processing and degradation
      and the coupled transport of small molecules. V-ATPases in the plasma membrane of
      specialized cells also function in such processes as renal acidification, bone
      resorption and pH homeostasis. Work from our laboratory has focused on the V
      ATPases from clathrin-coated vesicles and yeast vacuoles.Structurally, the V
      ATPases are composed of two domains: a peripheral complex (V(1)) composed of
      eight different subunits (A-H) that is responsible for ATP hydrolysis and an
      integral complex (V(0)) composed of five different subunits (a, d, c, c' and c")
      that is responsible for proton translocation. Electron microscopy has revealed
      the presence of multiple stalks connecting the V(1) and V(0) domains, and
      crosslinking has been used to address the arrangement of subunits in the complex.
      Site-directed mutagenesis has been employed to identify residues involved in ATP
      hydrolysis and proton translocation and to study the topology of the 100 kDa a
      subunit. This subunit has been shown to control intracellular targeting of the V
      ATPase and to influence reversible dissociation and coupling of proton transport
      and ATP hydrolysis.

PMID- 12206895
TI  - A turbo engine with automatic transmission? How to marry chemicomotion to the
      subtleties and robustness of life.
AB  - Most genomes are much more complex than required for the minimum chemistry of
      life. Evolution has selected sophistication more than life itself. Could this
      also apply to bioenergetics? We first examine mechanisms through which
      bioenergetics could deliver sophistication. We illustrate possible benefits of
      the turbo-charging of catabolic pathways, of loose coupling, low-gear catabolism,
      automatic transmission in energy coupling, and of homeostasis. Mechanisms for
      such phenomena may reside at the level of individual proton pumps, or consist of
      rerouting of electrons over parallel pathways. The mechanisms may be confined to
      preexisting components, or involve the plasticity of gene expression that is so
      characteristic of most living organisms. These possible benefits lead us to the
      conjecture that also bioenergetics has evolved more for sophistication than for
      necessity. We next discuss a hitherto unresolved enigma, i.e. that bioenergetics
      does not seem to be critical for the physiological state. To decide on how
      critical bioenergetics is, we quantified the control exerted by catabolism on
      important physiological functions such as growth rate and growth yield. We also
      determined whether a growth inhibition mostly affected bioenergetics (catabolism)
      or anabolism; if ATP increases with growth rate, then growth should be considered
      energy (catabolism) limited. The experimental results for Escherichia coli
      pinpoint the enigma: its energy metabolism (catabolism) is not critical for
      growth rate. These results might suggest that because it has no direct control
      over cell function, bioenergetics is unimportant. Paradoxically however, in
      biology, highly important mechanisms tend to have little control on cell
      function, precisely because of that importance. Sophistication in terms of
      homeostatic mechanisms has evolved to guarantee robustness of the most important
      functions: The most important mechanisms are redundant in biology. Bioenergetics
      may be an excellent example of this paradox, in line with the above conjecture.
      It may be highly important and sophisticated. We then discuss work that has begun
      to focus on the sophistication of bioenergetics. Homeostasis of the energetics of
      DNA structure in E. coli is extensive. It relies both on preexisting components
      and on responsive gene expression. The vastly parallel electron-transfer network
      of Paracoccus denitrificans engages in sophisticated dynamic and hierarchical
      regulation. The growth yield of the organism can depend on which terminal
      oxidases are active. Effective proton translocation may vary due to rerouting of
      electrons. We conclude that much sophistication of bioenergetics will be
      discovered in this era of functional genomics.

PMID- 12206896
TI  - Yarrowia lipolytica, a yeast genetic system to study mitochondrial complex I.
AB  - The obligate aerobic yeast Yarrowia lipolytica is introduced as a powerful new
      model for the structural and functional analysis of mitochondrial complex I. A
      brief introduction into the biology and the genetics of this nonconventional
      yeast is given and the relevant genetic tools that have been developed in recent
      years are summarized. The respiratory chain of Y. lipolytica contains complexes I
      IV, one "alternative" NADH-dehydrogenase (NDH2) and a non-heme alternative
      oxidase (AOX). Because the NADH binding site of NDH2 faces the mitochondrial
      intermembrane space rather than the matrix, complex I is an essential enzyme in
      Y. lipolytica. Nevertheless, complex I deletion strains could be generated by
      attaching the targeting sequence of a matrix protein, thereby redirecting NDH2 to
      the matrix side. Deletion strains for several complex I subunits have been
      constructed that can be complemented by shuttle plasmids carrying the deleted
      gene. Attachment of a hexa-histidine tag to the NUGM (30 kDa) subunit allows fast
      and efficient purification of complex I from Y. lipolytica by affinity
      chromatography. The purified complex has lost most of its NADH:ubiquinone
      oxidoreductase activity, but is almost fully reactivated by adding 400-500
      molecules of phosphatidylcholine per complex I. The established set of genetic
      tools has proven useful for the site-directed mutagenesis of individual subunits
      of Y. lipolytica complex I. Characterization of a number of mutations already
      allowed for the identification of several functionally important amino acids,
      demonstrating the usefulness of this approach.

PMID- 12206897
TI  - The dual-function glutamate transporters: structure and molecular
      characterisation of the substrate-binding sites.
AB  - Glutamate transporters are essential for terminating synaptic excitation and for
      maintaining extracellular glutamate concentrations below neurotoxic levels. These
      transporters also mediate a thermodynamically uncoupled chloride flux, activated
      by two of the molecules they transport, sodium and glutamate. Five eukaryotic
      glutamate transporters have been cloned and identified. They exhibit
      approximately 50% identity and this homology is even greater at the carboxyl
      terminal half, which is predicted to have an unusual topology. Determination of
      the topology shows that the carboxyl terminal part contains several transmembrane
      domains separated by two reentrant loops that are in close proximity to each
      other. We have identified several conserved amino acid residues in the carboxyl
      terminal half that play crucial roles in the interaction of the transporter with
      its substrates: sodium, potassium and glutamate. The conformation of the
      transporter gating the anion conductance is different from that during substrate
      translocation. However, there exists a dynamic equilibrium between these
      conformations.

PMID- 12206898
TI  - Influence of structure, pH and membrane potential on proton movement in
      cytochrome oxidase.
AB  - Cytochrome c oxidase (CcO) reconstituted into phospholipid vesicles and subject
      to a membrane potential, exhibits different characteristics than the free enzyme,
      with respect to effects of mutations, pH, inhibitors, and native structural
      differences between CcO from different species. The results indicate that the
      membrane potential influences the conformation of CcO and the direction of proton
      movement in the exit path. The importance of the protein structure above the
      hemes in proton exit, back leak and respiratory control is discussed.

PMID- 12206899
TI  - Atp11p and Atp12p are chaperones for F(1)-ATPase biogenesis in mitochondria.
AB  - The bioenergetic needs of aerobic cells are met principally through the action of
      the F(1)F(0) ATP synthase, which catalyzes ATP synthesis during oxidative
      phosphorylation. The catalytic unit of the enzyme (F(1)) is a multimeric protein
      of the subunit composition alpha(3)beta(3)(gamma)(delta) epsilon. Our work, which
      employs the yeast Saccharomyces cerevisiae as a model system for studies of
      mitochondrial function, has provided evidence that assembly of the mitochondrial
      alpha and beta subunits into the F(1) oligomer requires two molecular chaperone
      proteins called Atp11p and Atp12p. Comprehensive knowledge of Atp11p and Atp12p
      activities in mitochondria bears relevance to human physiology and disease as
      these chaperone actions are now known to exist in mitochondria of human cells.

PMID- 12206900
TI  - Manipulation of mitochondrial DNA gene expression in the mouse.
AB  - Mitochondrial dysfunction due to impaired respiratory chain function is
      increasingly recognized as an important cause of human disease. Mitochondrial
      disorders are relatively common and have an estimated incidence of 1:10,000 live
      births. There are more than 100 different point mutations and numerous large
      rearrangements of mitochondrial DNA (mtDNA; mainly single deletions) that cause
      human disease. We aimed at obtaining an animal model to study physiological
      aspects of mtDNA mutation disorders. There are as yet unsolved technical problems
      associated with transfection of mammalian mitochondria. We therefore choose to
      manipulate mtDNA expression by targeting of the nuclear gene encoding Tfam. We
      utilised the cre-loxP recombination system to disrupt Tfam since this system
      allows manipulation of respiratory chain function in selected mouse tissues. We
      have found increased cell death or apoptosis induction in both germ line and
      tissue-specific Tfam knockouts. Our results further suggest that increased
      production of reactive oxygen species (ROS) is not a prominent feature in cells
      with impaired mtDNA expression.

PMID- 12206901
TI  - Combined in-gel tryptic digestion and CNBr cleavage for the generation of peptide
      maps of an integral membrane protein with MALDI-TOF mass spectrometry.
AB  - A limitation of the in-gel approaches for the generation of peptides of membrane
      proteins is the size and hydrophobicity of the fragments generated. For membrane
      proteins like the lactose transporter (LacS) of Streptococcus thermophilus,
      tryptic digestion or CNBr cleavage yields several hydrophobic fragments larger
      than 3.5 kDa. As a result, the sequence coverage of the membrane domain is low
      when the in-gel tryptic-digested or CNBr-cleaved fragments are analyzed by matrix
      assisted laser desorption/ionization-time-of-flight (MALDI-TOF) mass spectrometry
      (MS). The combination of tryptic digestion and subsequent CNBr cleavage on the
      same gel pieces containing LacS approximately doubled the coverage of the
      hydrophobic membrane domain compared to the individual cleavage methods, while
      the coverage of the soluble domain remained complete. The fragments formed are
      predominantly below m/z 2500, which allows accurate mass measurement.

PMID- 12206902
TI  - ATR-FTIR difference spectroscopy of the P(M) intermediate of bovine cytochrome c
      oxidase.
AB  - Perfusion-induced attenuated total reflection Fourier transform infrared (ATR
      FTIR) spectroscopy was used to investigate changes induced in protein and
      cofactors of bovine cytochrome c oxidase when it was converted from the oxidised
      state to the catalytic P(M) intermediate. The transition was induced in a film of
      detergent-depleted 'fast' oxidase with a buffer containing CO and O(2). The
      extent of formation of the P(M) state was quantitated simultaneously by
      monitoring formation of its characteristic 607-nm band with a scanned visible
      beam reflected off the top surface of the prism. The P(M) minus O FTIR difference
      spectrum is distinctly different from the redox spectra reported to date and
      includes features that can be assigned to changes of haem a(3) and surrounding
      protein. Tentative assignments are made based on vibrational data of related
      proteins and model compounds.

PMID- 12206903
TI  - The organization of the membrane domain and its interaction with the NADP(H)
      binding site in proton-translocating transhydrogenase from E. coli.
AB  - Proton-translocating nicotinamide nucleotide transhydrogenase is a
      conformationally driven pump which catalyzes the reversibel reduction of NADP(+)
      by NADH. Transhydrogenases contain three domains, i.e., the hydrophilic NAD(H)
      binding domain I and the NADP(H)-binding domain III, and the hydrophobic domain
      II containing the proton channel. Domains I and III have been separately
      expressed and characterized structurally by, e.g. X-ray crystallography and NMR.
      These domains catalyze transhydrogenation in the absence of domain II. However,
      due to the absence of the latter domain, the reactions catalyzed by domains I and
      III differ significantly from those catalyzed by the intact enzyme. Mutagenesis
      of residues in domain II markedly affects the activity of the intact enzyme. In
      order to resolve the structure-function relationships of the intact enzyme, and
      the molecular mechanism of proton translocation, it is therefore essential to
      establish the structure and function of domain II and its interactions with
      domains I and III. This review describes some relevant recent results in this
      field of research.

PMID- 12206904
TI  - Proton translocation by cytochrome c oxidase in different phases of the catalytic
      cycle.
AB  - Since mitochondrial cytochrome c oxidase was found to be a redox-linked proton
      pump, most enzymes of the haem-copper oxidase family have been shown to share
      this function. Here, the most recent knowledge of how the individual reactions of
      the enzyme's catalytic cycle are coupled to proton translocation is reviewed. Two
      protons each are pumped during the oxidative and reductive halves of the cycle,
      respectively. An apparent controversy that concerns proton translocation during
      the reductive half is resolved. If the oxidised enzyme is allowed to relax in the
      absence of reductant, the binuclear haem-copper centre attains a state that lies
      outside the main catalytic cycle. Reduction of this form of the enzyme is not
      linked to proton translocation, but is necessary for a return to the main cycle.
      This phenomenon might be related to the previously described "pulsed" vs.
      "resting" and "fast" vs."slow" forms of haem-copper oxidases.

PMID- 12206905
TI  - Inhibition of proton transfer in cytochrome c oxidase by zinc ions: delayed
      proton uptake during oxygen reduction.
AB  - We have investigated the effect of Zn ions on proton-transfer reactions in
      cytochrome c oxidase. In the absence of Zn(2+) the transition from the "peroxy"
      (P(R)) to the "ferryl" (F) intermediate has a time constant of approximately 100
      micros and it is associated with proton transfer from the bulk solution with an
      intrinsic time constant of <<100 micros, but rate limited by the P(R)-->F
      transition. While in the presence of 100 microM Zn(2+) the P(R)-->F transition
      was slowed by a factor of approximately 2, proton uptake from the bulk solution
      was impaired to a much greater extent. Instead, about two protons (one proton in
      the absence of Zn(2+)) were taken up during the next reaction step, i.e. the
      decay of F to the oxidized (O) enzyme with a time constant of approximately 2.5
      ms. Thus, the results show that there is one proton available within the enzyme
      that can be used for oxygen reduction and confirm our previous observation that F
      can be formed without proton uptake from the bulk solution. No effect of Zn(2+)
      was observed with a mutant enzyme in which Asp(I-132), at the entry point of the
      D-pathway, was replaced by its non-protonatable analogue Asn. In addition, no
      effect of Zn(2+) was observed on the F-->O transition rate when measured in
      D(2)O, because in D(2)O, the transition is internally slowed to approximately 10
      ms, which is already slower than with bound Zn(2+). Together with earlier results
      showing that both the P(R)-->F and F-->O transitions are associated with proton
      uptake through the D-pathway, the results from this study indicate that Zn(2+)
      binds to and blocks the entrance of the D-pathway.

PMID- 12206906
TI  - Molecular devices of chloroplast F(1)-ATP synthase for the regulation.
AB  - In chloroplasts, synthesis of ATP is energetically coupled with the utilization
      of a proton gradient formed by photosynthetic electron transport. The involved
      enzyme, the chloroplast ATP synthase, can potentially hydrolyze ATP when the
      magnitude of the transmembrane electrochemical potential difference of protons
      (Delta(micro)H(+)) is small, e.g. at low light intensity or in the dark. To
      prevent this wasteful consumption of ATP, the activity of chloroplast ATP
      synthase is regulated as the occasion may demand. As regulation systems
      Delta(micro)H(+) activation, thiol modulation, tight binding of ADP and the role
      of the intrinsic inhibitory subunit epsilon is well documented. In this article,
      we discuss recent progress in understanding of the regulation system of the
      chloroplast ATP synthase at the molecular level.

PMID- 12206907
TI  - The NDUFS4 nuclear gene of complex I of mitochondria and the cAMP cascade.
AB  - Results of studies on the role of the 18 kDa (IP) polypeptide subunit of complex
      I, encoded by the nuclear NDUFS4 gene, in isolated bovine heart mitochondria and
      human and murine cell cultures are presented.The mammalian 18 kDa subunit has in
      the carboxy-terminal sequence a conserved consensus site (RVS), which in isolated
      mitochondria is phosphorylated by cAMP-dependent protein kinase (PKA). The
      catalytic and regulatory subunits of PKA have been directly immunodetected in the
      inner membrane/matrix fraction of mammalian mitochondria. In the mitochondrial
      inner membrane a PP2Cgamma-type phosphatase has also been immunodetected, which
      dephosphorylates the 18 kDa subunit, phosphorylated by PKA. This phosphatase is
      Mg(2+)-dependent and inhibited by Ca(2+). In human and murine fibroblast and
      myoblast cultures "in vivo", elevation of intracellular cAMP level promotes
      phosphorylation of the 18 kDa subunit and stimulates the activity of complex I
      and NAD-linked mitochondrial respiration. Four families have been found with
      different mutations in the cDNA of the NDUFS4 gene. These mutations, transmitted
      by autosomal recessive inheritance, were associated in homozygous children with
      fatal neurological syndrome. All these mutations destroyed the phosphorylation
      consensus site in the C terminus of the 18 kDa subunit, abolished cAMP activation
      of complex I and impaired its normal assembly.

PMID- 12206908
TI  - Respiratory chain supercomplexes of mitochondria and bacteria.
AB  - Respiratory chain complexes are fragments of larger structural and functional
      units, the respiratory chain supercomplexes or "respirasomes", which exist in
      bacterial and mitochondrial membranes. Supercomplexes of mitochondria and
      bacteria contain complexes III, IV, and complex I, with the notable exception of
      Saccharomyces cerevisiae, which does not possess complex I. These supercomplexes
      often are stable to sonication but sensitive to most detergents except digitonin.
      In S. cerevisiae, a major component linking complexes III and IV together is
      cardiolipin.In Paracoccus denitrificans, complex I itself is rather detergent
      sensitive and thus could not be obtained in detergent-solubilized form so far.
      However, it can be isolated as part of a supercomplex. Stabilization of complex I
      by binding to complex III was also found in human mitochondria. Further
      functional roles of the organization in a supercomplex are catalytic enhancement
      by reducing diffusion distances of substrates or, depending on the organism,
      channelling of the substrates quinone and cytochrome c. This makes redox
      reactions less dependent of midpoint potentials of substrates, and permits
      electron flow at low degree of substrate reduction.A dimeric state of ATP
      synthase seems to be specific for mitochondria. Exclusively, monomeric ATP
      synthase was found in Acetobacterium woodii, in P. denitrificans, and in spinach
      chloroplasts.

PMID- 12206909
TI  - Effects of fatty acids on mitochondria: implications for cell death.
AB  - Fatty acids have prominent effects on mitochondrial energy coupling through at
      least three mechanisms: (i) increase of the proton conductance of the inner
      mitochondrial membrane; (ii) respiratory inhibition; (iii) opening of the
      permeability transition pore (PTP). Furthermore, fatty acids physically interact
      with membranes and possess the potential to alter their permeability; and they
      are also excellent respiratory substrates that feed electrons into the
      respiratory chain. Due to the complexity of their actions, the effects of fatty
      acids on mitochondrial function in situ are difficult to predict. We have
      investigated the mitochondrial and cellular effects of fatty acids of increasing
      chain length and degree of unsaturation in relation to their potential to affect
      mitochondrial function in situ and to cause cell death. We show that saturated
      fatty acids have little effect on the mitochondrial membrane potential in situ,
      and display negligible short-term cytotoxicity for Morris Hepatoma 1C1 cells. The
      presence of double bonds increases both the depolarizing effects and the
      cytotoxicity, but these effects are offset by the hydrocarbon chain length, so
      that more unsaturations are required to observe an effect as the hydrocarbon
      chain length is increased. With few exceptions, depolarization and cell death are
      due to opening of the PTP rather than to the direct effects of fatty acids on
      energy coupling.

PMID- 12206910
TI  - A concerted, alternating sites mechanism of ubiquinol oxidation by the dimeric
      cytochrome bc(1) complex.
AB  - A refinement of the protonmotive Q cycle mechanism is proposed in which oxidation
      of ubiquinol is a concerted reaction and occurs by an alternating, half-of-the
      sites mechanism. A concerted mechanism of ubiquinol oxidation is inferred from
      the finding that there is reciprocal control between the high potential and low
      potential redox components involved in ubiquinol oxidation. The potential of the
      Rieske iron-sulfur protein controls the rate of reduction of the b cytochromes,
      and the potential of the b cytochromes controls the rate of reduction of the
      Rieske protein and cytochrome c(1). A concerted mechanism of ubiquinol oxidation
      reconciles the findings that the ubiquinol-cytochrome c reductase kinetics of the
      bc(1) complex include both a pH dependence and a dependence on Rieske iron-sulfur
      protein midpoint potential.An alternating, half-of-the-sites mechanism for
      ubiquinol oxidation is inferred from the finding that some inhibitory analogs of
      ubiquinol that block ubiquinol oxidation by binding to the ubiquinol oxidation
      site in the bc(1) complex inhibit the yeast enzyme with a stoichiometry of 0.5
      per bc(1) complex. One molecule of inhibitor is sufficient to fully inhibit the
      dimeric enzyme, and the binding is anti-cooperative, in that a second molecule of
      inhibitor binds with much lower affinity to a dimer in which an inhibitor
      molecule is already bound. An alternating, half-of-the-sites mechanism implies
      that, at least under some conditions, only half of the sites in the dimeric
      enzyme are reactive at any one time. This provides a raison d'etre for the
      dimeric structure of the enzyme, in that bc(1) activity may be regulated and
      capable of switching between a half-of-the-sites active and a fully active
      enzyme.

PMID- 12206911
TI  - Is there a relationship between the supramolecular organization of the
      mitochondrial ATP synthase and the formation of cristae?
AB  - Blue native polyacrylamide gel electrophoresis (BN-PAGE) analyses of detergent
      mitochondrial extracts have provided evidence that the yeast ATP synthase could
      form dimers. Cross-linking experiments performed on a modified version of the i
      subunit of this enzyme indicate the existence of such ATP synthase dimers in the
      yeast inner mitochondrial membrane. We also show that the first transmembrane
      segment of the eukaryotic b-subunit (bTM1), like the two supernumerary subunits e
      and g, is required for dimerization/oligomerization of ATP synthases. Unlike
      mitochondria of wild-type cells that display a well-developed cristae network,
      mitochondria of yeast cells devoid of subunits e, g, or bTM1 present
      morphological alterations with an abnormal proliferation of the inner
      mitochondrial membrane. From these observations, we postulate that an anomalous
      organization of the inner mitochondrial membrane occurs due to the absence of ATP
      synthase dimers/oligomers. We provide a model in which the mitochondrial ATP
      synthase is a key element in cristae morphogenesis.

PMID- 12206912
TI  - Aquaglyceroporins, one channel for two molecules.
AB  - In the light of the recently published structure of GlpF and AQP1, we have
      analysed the nature of the residues which could be involved in the formation of
      the selectivity filter of aquaporins, glycerol facilitators and
      aquaglyceroporins. We demonstrate that the functional specificity for major
      intrinsic protein (MIP) channels can be explained on one side by analysing the
      polar environment of the residues that form the selective filter. On the other
      side, we show that the channel selectivity could be associated with the
      oligomeric state of the membrane protein. We conclude that a non-polar
      environment in the vicinity of the top of helix 5 could allow aquaglyceroporins
      and GlpF to exist as monomers within the hydrophobic environment of the membrane.

PMID- 12206913
TI  - From NADH to ubiquinone in Neurospora mitochondria.
AB  - The respiratory chain of the mitochondrial inner membrane includes a proton
      pumping enzyme, complex I, which catalyses electron transfer from NADH to
      ubiquinone. This electron pathway occurs through a series of protein-bound
      prosthetic groups, FMN and around eight iron-sulfur clusters. The high number of
      polypeptide subunits of mitochondrial complex I, around 40, have a dual genetic
      origin. Neurospora crassa has been a useful genetic model to characterise complex
      I. The characterisation of mutants in specific proteins helped to understand the
      elaborate processes of the biogenesis, structure and function of the oligomeric
      enzyme. In the fungus, complex I seems to be dispensable for vegetative growth
      but required for sexual development. N. crassa mitochondria also contain three to
      four nonproton-pumping alternative NAD(P)H dehydrogenases. One of them is located
      in the outer face of the inner mitochondrial membrane, working as a calcium
      dependent oxidase of cytosolic NADPH.

PMID- 12206914
TI  - A replicating module as the unit of mitochondrial structure and functioning.
AB  - The mitochondrion within human cells in tissue culture is pleomorphic and highly
      dynamic. The organelle mass can exist as thousands of small ovoids or as one
      continuous reticulum. In either state, the mitochondrial mass is in constant
      thermal motion, as well as moving in approximately 0.8-microm jumps that are
      determined by, and related to, attachments with cytoskeletal elements. Many
      protein complexes, such as the pyruvate dehydrogenase (PDH) complex and DNA
      containing nucleoids, are dispersed through the mass and as though fixed by
      attachments to membranes, such that they can become distributed to all of the
      individual small ovoid mitochondria when the reticulum becomes fragmented. This
      leads us to propose that a replicating module is the repeating unit of
      mitochondrial structure. Studies to examine heterogeneity of functioning within
      the organelle mass are briefly reviewed.

PMID- 12206915
TI  - Insight into mitochondrial structure and function from electron tomography.
AB  - In recent years, electron tomography has provided detailed three-dimensional
      models of mitochondria that have redefined our concept of mitochondrial
      structure. The models reveal an inner membrane consisting of two components, the
      inner boundary membrane (IBM) closely apposed to the outer membrane and the
      cristae membrane that projects into the matrix compartment. These two components
      are connected by tubular structures of relatively uniform size called crista
      junctions. The distribution of crista junction sizes and shapes is predicted by a
      thermodynamic model based upon the energy of membrane bending, but proteins
      likely also play a role in determining the conformation of the inner membrane.
      Results of structural studies of mitochondria during apoptosis demonstrate that
      cytochrome c is released without detectable disruption of the outer membrane or
      extensive swelling of the mitochondrial matrix, suggesting the formation of an
      outer membrane pore large enough to allow passage of holo-cytochrome c. The
      possible compartmentation of inner membrane function between the IBM and the
      cristae membrane is also discussed.

PMID- 12206916
TI  - The ferredoxin docking site of photosystem I.
AB  - The reaction center of photosystem I (PSI) reduces soluble ferredoxin on the
      stromal side of the photosynthetic membranes of cyanobacteria and chloroplasts.
      The X-ray structure of PSI from the cyanobacterium Synechococcus elongatus has
      been recently established at a 2.5 A resolution [Nature 411 (2001) 909]. The
      kinetics of ferredoxin photoreduction has been studied in recent years in many
      mutants of the stromal subunits PsaC, PsaD and PsaE of PSI. We discuss the
      ferredoxin docking site of PSI using the X-ray structure and the effects brought
      by the PSI mutations to the ferredoxin affinity.

PMID- 12206918
TI  - Quality of life instruments in studies of menorrhagia: a systematic review.
AB  - BACKGROUND: The use of quality of life (QoL) instruments in menorrhagia research
      is increasing but there is concern that not enough emphasis is placed on patient
      focus in these measurements, i.e. on issues which are of importance to patients
      and reflect their experiences and concerns (clinical face validity). The
      objective was to assess the quality of QoL instruments in studies of menorrhagia.
      STUDY DESIGN: A systematic review of published research. Papers were identified
      through MEDLINE (1966-April 2000), EMBASE (1980-April 2000), Science Citation
      Index (1981-April 2000), Social Science Citation Index (1981-April 2000), CINAHL
      (1982-1999) and PsychLIT (1966-1999), and by manual searching of bibliographies
      of known primary and review articles. Studies were selected if they assessed
      women with menorrhagia for life quality, either developing QoL instruments or
      applying them as an outcome measure. Selected studies were assessed for quality
      of their QoL instruments, using a 17 items checklist including 10 items for
      clinical face validity (issues of relevance to patients' expectations and
      concerns) and 7 items for measurement properties (such as reliability,
      responsiveness, etc.). RESULTS: A total of 19 articles, 8 on instrument
      development and 11 on application, were included in the review. The generic Short
      Form 36 Health Survey Questionnaire (SF36) was used in 12/19 (63%) studies. Only
      two studies developed new specific QoL instruments for menorrhagia but they
      complied with 7/17 (41%) and 10/17 (59%) of the quality criteria. Quality
      assessment showed that only 7/19 (37%) studies complied with more than half the
      criteria for face validity whereas 17/19 (90%) studies complied with more than
      half of the criteria for measurement properties (P = 0.0001). CONCLUSION: Among
      existing QoL instruments, there is good compliance with the quality criteria for
      measurement properties but not with those for clinical face validity. There is a
      need to develop methodologically sound disease specific QoL instruments in
      menorrhagia focussing both on face validity and measurement properties.

PMID- 12206919
TI  - Simultaneous use of intrapartum fetal pulse oximetry and amnioinfusion in
      meconium stained amniotic fluid.
AB  - OBJECTIVE: Fetal pulse oximetry is a minimally invasive, simple technique which
      continuously helps to reflect in utero well-being. The presence of meconium in
      the amniotic fluid may be a clinical sign of fetal hypoxaemia. Amnioinfusion has
      a beneficial effect on the incidence of meconium aspiration syndrome (MAS), and
      the presence of meconium below the level of the vocal cords. STUDY DESIGN: We
      studied the impact of amnioinfusion combined with fetal pulse oximetry on the
      incidence of meconium aspiration syndrome and operative delivery. RESULTS: The
      retrospective analysis revealed that the presence of meconium below the level of
      vocal cords was significantly reduced. The frequency of cesarean section is
      decreased, however, it did not reach statistical significance. CONCLUSION: Fetal
      pulse oximetry may be used in combination with amnioinfusion and cardiotocography
      (CTG) to reduce the risk of meconium aspiration syndrome and the number of
      instrumental deliveries and improve perinatal outcome.

PMID- 12206920
TI  - Multidrug resistance 3 gene mutation 1712delT and estrogen receptor alpha gene
      polymorphisms in Finnish women with obstetric cholestasis.
AB  - OBJECTIVE: To investigate the contribution of the estrogen receptor alpha
      (ERalpha) polymorphism in the development of obstetric cholestasis and to
      determine whether multidrug resistance 3 (MDR3) gene 1712delT mutation detected
      in French patients is also present in Finnish women with obstetric cholestasis.
      STUDY DESIGN: In a retrospective case-control study, two ERalpha polymorphisms
      and MDR3 gene mutation 1712delT were investigated in healthy control women (N =
      47) and in women with diagnosis of obsteric cholestasis (N = 57). PvuII and XbaI
      polymorphisms in ERalpha gene were evaluated in genomic DNA by using the
      polymerase chain reaction (PCR). In addition, the frequencies in the general
      population in our area are presented for comparison. RESULTS: None of the ERalpha
      genotypes or alleles was significantly over-represented in obstetric cholestasis.
      When the two ERalpha gene polymorphisms were analyzed in parallel, six genotype
      combinations were recognized, and the distribution of these genotype combinations
      did not reveal statistically significant differences between the cases and
      controls (P = 0.612). No patient or control was heterozygous or homozygous for
      the mutant allele in the MDR3 gene. CONCLUSION: The present data indicate that
      polymorphism of the ERalpha gene and MDR3 gene 1712delT mutation are unlikely to
      play any significant role in obstetric cholestasis in affected Finnish women.
      Further work to identify explanatory factors is of particular interest.

PMID- 12206921
TI  - A comparison of clinical assessment with ultrasound in the management of
      secondary postpartum haemorrhage.
AB  - OBJECTIVE: To compare the diagnostic accuracy of clinical assessment with
      transabdominal ultrasound in the management of secondary postpartum haemorrhage
      (PPH). DESIGN: A prospective cohort study. METHODS: Fifty-three women who
      presented to a teaching hospital obstetric unit with secondary PPH were studied.
      Patients were divided into those in whom retained placental tissue was or was not
      the suspected cause of bleeding. This diagnosis was based on history/examination
      and transabdominal pelvic ultrasound scan. The definitive diagnosis was made
      following uterine evacuation or was assumed in women who stopped bleeding without
      surgical management. Likelihood ratio (LR) was used as an accuracy measure.
      RESULTS: The positive LR for clinical assessment was 5.5 (95% CI 2.7-12.1)
      compared with 2.4 (95% CI 1.5-3.7) for ultrasound. The negative LRs were 0.1 (95%
      CI 0.04-0.5) and 0.1 (95% CI 0.02-0.5) for clinical and ultrasound assessment,
      respectively. CONCLUSION: Clinical examination and ultrasound scan assessment
      have limited diagnostic accuracy in secondary PPH.

PMID- 12206922
TI  - Prepidil compared to Propess for cervical ripening.
AB  - OBJECTIVES: To compare the efficacy and safety of intracervical PGE(2) gel
      (Prepidil) with intravaginal PGE(2) insert (Propess) in cervical ripening and
      induction of labour. STUDY DESIGN: This was a retrospective analysis of patients
      with single pregnancies, intact membranes and a viable fetus who required
      cervical ripening. In the first half of 1998, all patients received Prepidil and
      in the first half of 1999 all patients received Propess. In both periods 50
      consecutive files were retrieved and compared. RESULTS: The Prepidil and Propess
      group were similar in patient characteristics, indication for induction of labour
      and delivery outcome. Cervical ripening within 24 h was achieved in the Propess
      group in 80% as compared to 56% in the Prepidil group. The application-membrane
      rupture-interval was shorter in the Propess group compared to the Prepidil group
      (23.7 +/- 21.3 h versus 56.4 +/- 77.7 h, P = 0.009) as well as the application
      delivery interval (29.8 +/- 22.0 h versus 62.0 +/- 78.8 h, P = 0.039). In the
      Propess group 62% delivered within 24 h compared to 28% in the Prepidil group. A
      smaller number of applications was observed in the Propess group (1.2 versus 1.8,
      P < 0.005). Both methods proved to be safe in cervical priming and no relevant
      differences in mode of delivery and outcome of labour were detected. None of the
      patients required an emergency caesarean section during the treatment with
      prostaglandines. CONCLUSIONS: Both prostaglandin E(2) agents are safe and
      effective in achieving cervical ripening; however the vaginal insert demonstrated
      a shorter application-delivery interval. The hospital stay was consequently
      shorter, contributing to cost effectiveness.

PMID- 12206923
TI  - Pre-term cervical ripening and labor induction.
AB  - OBJECTIVE: To evaluate retrospectively pre-term induction; with Prostaglandin
      (PG) E(2)-gel and i.v. oxtytocin, respectively. METHODS: Fifty pre-term women
      with a gestational age between 28 + 0 and 36 + 6 and medical indications for
      labor induction were compared with the two next induced at term and post-term.
      The obstetric end points were numbers of PGE(2)-gel applications, failed
      inductions, instrumental delivery and heavy bleeding after partus (>1000 ml). The
      neonatal outcome was registered as operative delivery for fetal distress (ODFD)
      or Apgar score <7 at 5'. RESULTS: The number of PGE(2)-gel applications did not
      differ. The duration of labor was shorter in the pre-term group (P = 0.043). A
      five-fold higher risk of heavy postpartum bleeding (>1000 ml) was noticed in the
      post-term group compared to the pre-term. The incidence of low Apgar scores were
      similar in the three groups. CONCLUSIONS: Safe vaginal labor induction and
      delivery can be anticipated pre-term with PGE(2)-gel.

PMID- 12206924
TI  - Changing trends in pregnancy outcome among HIV-infected women between 1985 and
      1997 in two southern French university hospitals.
AB  - OBJECTIVES: To analyze risk factors for pregnancy outcome among HIV-infected
      women before and after introduction of AZT prophylaxis in 1994. STUDY DESIGN: A
      prospective, two-center observational study conducted from 1 January 1985 to 31
      December 1997. PATIENTS: Pregnant HIV-infected women followed in one of the
      obstetrics units during the study period. MAIN OUTCOME MEASURES: pregnancy
      outcome (normal delivery, ectopic pregnancy, spontaneous abortion, voluntary
      termination of pregnancy (TOP) according to year of pregnancy, age at pregnancy
      professional status, marital status, ethnic origin, mode of contamination, stage
      of disease, partner's human immunodeficiency virus (HIV) status and prior
      pregnancy. RESULTS: One thousand one hundred and three pregnancies among 937 HIV
      infected women were studied. Mean age of patients was 28.1 +/- 4.9 years.
      Pregnancy outcomes were distributed as follows: 473 normal deliveries, 589 TOP, 9
      ectopic pregnancies and 32 spontaneous abortions. The proportion of TOP decreased
      from 59.4% before 1994 to 37.5% from 1994 (P < 0.001). In univariate analysis,
      mode of transmission, marital status, ethnic origin, partner's HIV status and
      prior pregnancy were also significantly correlated with pregnancy outcome.
      However, after adjustment by logistic regression for each period (before and
      after 1994), mode of transmission no longer appeared to influence pregnancy
      outcome. CONCLUSION: Effective prevention of mother-to-child transmission of HIV
      infection appears to have influenced HIV-infected women's decisions on continuing
      their pregnancy to term. Incidence of voluntary TOP has decreased significantly
      after introduction of AZT.

PMID- 12206925
TI  - Comparison of the ICSI outcome of ejaculated sperm with normal, abnormal
      parameters and testicular sperm.
AB  - OBJECTIVE(S): To compare fertilization rates, quality of embryos, pregnancy rates
      (PRs) and outcome of pregnancies in intracytoplasmic sperm injection (ICSI) using
      sperm from ejaculates of normal and abnormal semen and testicular sperm of non
      obstructive azoospermia. STUDY DESIGN: Four hundred fifty-four patients who
      underwent 454 ICSI cycles were evaluated retrospectively. Patients were divided
      into three groups according to the quality and source of sperm. Patients in group
      1 underwent 133 cycles of ICSI using ejaculated normal semen, group 2 underwent
      235 cycles using ejaculated abnormal semen, and group 3 underwent 86 cycles using
      testicular sperm. RESULTS: The parameters were compared among the groups with
      respect to cycles induced by long (n = 160) and short (n = 294) protocol. In
      group 3, the fertilization and PRs were significantly lower than in all other
      groups (51.3 and 10.6% in the long protocol cycles, 53.3 and 5.1% in the short
      protocol cycles, respectively). There was no significant difference in the
      outcome of pregnancies in respect to abortion rates between different groups.
      CONCLUSION(S): The fertilizing ability of sperm in ICSI is highest with
      ejaculated sperm and lowest with sperm extracted by testicular biopsy. Also, the
      clinical PRs are significantly lower in ICSI with sperm from testicular biopsy.
      However, the outcomes of pregnancies are not affected by using surgically
      retrieved sperm from ejaculated semen.

PMID- 12206926
TI  - Endometrial vascularity and ongoing pregnancy after IVF.
AB  - BACKGROUND: Embryo transfer is prone to failure. AIM: To investigate whether
      endometrial vascularity influences in vitro fertilization (IVF) outcome. METHODS:
      Total 144 patients receiving IVF (conventional or microinjection) were assessed
      with color and power Doppler on the day of embryo transfer: age, IVF type, number
      and quality of embryos, endometrial thickness and aspect, mean uterine PI,
      uterine notch, type of endometrial vascularity (peripheral or sub- and intra
      endometrial), and pregnancy involving second trimester were recorded. RESULTS: 27
      (18.7%) pregnancies were obtained. By univariate analysis, two parameters were
      significant: high frequency of uterine notch (P = 0.03) and peri-endometrial
      vascularity (P = 0.012) in the group of failures. Multivariate analysis by
      logistic regression clearly showed that the absence of sub- and intra-endometrial
      color signal decreased the chances of pregnancy eight-fold odds ratio (OR) = 0.14
      [CI: 0.029-0.68]. CONCLUSION: In this limited series, the presence of sub- and
      intra-endometrial vascularity on the day of transfer seemed to be mandatory for
      obtaining an ongoing pregnancy.

PMID- 12206927
TI  - Risk factors for cervical stenosis after laser cone biopsy.
AB  - OBJECTIVE: To evaluate the incidence of cervical stenosis after laser cone biopsy
      and to identify risks factors for this adverse outcome. METHODS: Prospective
      study evaluating all patients (n = 375) treated by laser cone biopsy for
      suspected cervical intraepithelial neoplasia between 1 January 1990 and 31
      December 1996. Patients were contacted by mail for a clinical evaluation, 37 +/-
      26 months after surgery. Two hundred and thirty-eight patients (63%) reply to
      this clinical follow-up examination including colposcopy, cervical smear and
      evaluation of cervical stenosis. Cervical stenosis was defined as cervical os
      narrowing preventing the insertion of a cotton swab. RESULTS: Forty patients
      (16.8%) had cervical stenosis at follow-up. The risk of postoperative cervical
      stenosis increases when patients were older (mean age of women with stenosis 42
      years versus 35 years; P < 0.0001), when the depth of surgical excision increases
      (mean surgical specimen height 18.2 mm in women with stenosis versus 15.9 mm; P <
      0.01), when preoperative junction was endocervical (2.5; 95% confidence interval
      (CI) 1.4-4.7), when vaginal packing was necessary (2.4; 95% CI 1.4-4.2), and when
      continuous laser mode was used (2.1; 95% CI 1.2-3.7). Stenosis incidence was
      lower when human papilloma virus (HPV) was present on cervical biopsy (0.47; 95%
      CI 0.3-0.8), when women were smokers (0.48; 95% CI 0.3-0.9), and when a Surgicel
      compress was placed in the excision site (0,4; 95% CI 0.2-0.8). Patient age was
      the only significant independent predictor of stenosis identified by a
      multivariate analysis using logistic regression. CONCLUSIONS: Patient with
      advanced age should be counselled regarding the risks for cervical stenosis after
      laser cone biopsy. Other surgical options may be considered when patient age
      exceeds 40 years.

PMID- 12206928
TI  - Hysterectomy: surgical route and complications.
AB  - OBJECTIVES: To compare the morbidity associated with abdominal, vaginal and
      laparoscopic hysterectomies in a group of patients suitable for anyone of these
      surgical routes. STUDY DESIGN: Retrospective analysis of 1000 consecutive
      hysterectomies. RESULTS: The 513 patients were deemed to be suitable for
      hysterectomy by anyone of the three surgical routes. The overall complication
      rates were 34, 24 and 21% for abdominal, vaginal and laparoscopic hysterectomy,
      respectively. Multiple regression analysis showed that the morbidity was similar
      when confounding factors were allowed for, in particular the use of peri
      operative antibiotics. CONCLUSIONS: The route of hysterectomy is not a major
      determining factor of peri-operative complications when other confounding
      variables are taken into account.

PMID- 12206929
TI  - The role of intra-peritoneal honey administration in preventing post-operative
      peritoneal adhesions.
AB  - OBJECTIVE(S): The accelerative effect of honey in the wound healing process is
      known. This effect is related to its specific physical properties of
      hygroscopicity, hypertonicity, lower pH and complex chemical composition. Because
      peritoneal healing is a kind of wound healing process we hypothesised that post
      operative peritoneal adhesions (PPA) may be reduced with intra-peritoneal honey
      administration. STUDY DESIGN: The study was conducted with 40, 6-month-old, out
      bred female Wistar albino rats with a mean weight of 197 +/- 12 g. The rats were
      divided into two equal groups. An adhesion model was constituted in the cecum and
      terminal ileum of all rats in each groups. Later the adhesion areas were washed
      with 0.9% NaCl solution and 5 ml of the same solution was left in the peritoneal
      cavity in the control group. The same area in the rats in the other group was
      covered with honey and 5 ml of honey was left in the peritoneal cavity of each
      animals. Ten days later the rats were sacrificed and the adhesions were graded
      according to their degree of severity. Statistical analysis was performed with
      the non-parametric Mann-Whitney U-test. RESULTS: In the control group, there were
      no rats with grade-0 or grade-1 adhesions but in the honey administered group
      there were six rats (30%) with grade-0 and 12 rats (60%) with grade-1 adhesions.
      In the control group, there were six rats (30%) with grade-2 and 14 rats (70%)
      with grade-3 adhesions. In the honey administered group while two rats (10%) with
      grade-2 adhesions were present, no rat with grade-3 adhesions was seen. In the
      comparison, the difference between the groups was found to be highly significant
      (P < 0.001). CONCLUSION(S): The wound healing accelerative effect and the
      mechanical barrier formed by the honey, since, it has a high density and, thus,
      absorbed slowly from peritoneal cavity, may be the reasons for its inhibitory
      effect on the PPA. This study indicates that though the mechanism is not clear
      intra-peritoneal honey administration reduces PPA.

PMID- 12206930
TI  - Low Vitamin B(12) level as a risk factor for very early recurrent abortion.
AB  - OBJECTIVE: To examine the relationship between Vitamin B(12) deficiency and early
      recurrent abortion (ERA) or very early recurrent abortion (VERA) abortion around
      5 weeks of amenorrhea. STUDY DESIGN: Serum B(12), folate and homocysteine levels
      were carried out in 110 consecutive women with unexplained ERA or VERA and in 96
      women with one or more children and no abortion history. RESULTS: Ten women were
      found to have low serum B(12) levels versus one in the control group. A total of
      50% of these had raised homocysteine. No difference was noticed between cases and
      controls for folate. Among women with low serum B(12) level and ERA, 87.5% of the
      abortions were VERA. Vitamin B(12) supplementation led to four normal pregnancies
      in five women who became pregnant again. In a statistical analysis performed on
      five studies in which serum B(12) was assayed in ERA, including ours, a
      significant relationship was found between ERA and Vitamin B(12) deficiency.
      CONCLUSION: Vitamin B(12) deficiency may be involved in ERA. Vitamin B(12) assay
      should be done in ERA women whether or not hematological abnormalities are
      present.

PMID- 12206931
TI  - A multicenter survey of complications associated with 21,676 operative
      hysteroscopies.
AB  - OBJECTIVE: The following study analyses the hysteroscopic experience of multiple
      gynecologic centers throughout Germany in regard to the incidence of
      complications, the therapy of these complications and anesthesiological
      management during 21,676 hysteroscopic procedures. METHODS AND MATERIAL: Under
      the supervision of the German Society of Gynecology Endoscopy, 92 hysteroscopic
      centers were evaluated and the following information was collected: hysteroscopic
      experience in years, number of surgical hysteroscopies per year, total number of
      operative hysteroscopies, types of hysteroscopic procedures, intra- and post
      operative complications. RESULTS AND CONCLUSION: The results of the study show
      that in most German centers, hysteroscopy is just being established.
      Nevertheless, the rate of complications such as perforation of the uterus, fluid
      overload syndrome, infection and perioperative bleeding is small. This may be due
      to the high proportion of documented procedures performed by the more experienced
      centers.

PMID- 12206932
TI  - Variable response of Hermansky-Pudlak syndrome to prophylactic administration of
      1-desamino 8D-arginine in subsequent pregnancies.
AB  - Hermansky-Pudlak syndrome is characterised by oculocutaneous albinism and
      haemorrhagic diathesis. The bleeding tendency that is associated with this
      autosomal recessive disease is caused by storage-pool deficiency and has been
      reported to be controllable by prophylactic administration of 1-desamino 8D
      arginine (desmopressin, DDAVP). The DDAVP prophylaxis at the first delivery of
      our patient did not prevent the severe haemorrhagic sequeal requiring transfusion
      of packed red cells and platelets, but the same preventive measure was successful
      at her second childbirth. Response to prophylactic DDAVP administration varies
      between as well as within patients with Hermansky-Pudlak syndrome.

PMID- 12206933
TI  - Two kinds of endometrial neoplasia arising from different origins in the uterine
      corpus: comparison of p53 expression and sex steroid receptor status.
AB  - This study presents a case of endometrial clear cell adenocarcinoma complicated
      by complex atypical glandular hyperplasia surrounded by adenomyosis in the
      uterine myometrium. The former was immuno-negative for estrogen receptor (ER) and
      positive for p53, whereas both of the latter were immuno-positive for ER and
      negative for p53. Therefore, there were two kinds of neoplasia arising from
      different origins in the uterine corpus.

PMID- 12206934
TI  - Premenopausal metrorrhagia as a symptom of sarcoidosis.
AB  - Sarcoidosis rarely affects the female genitalia. We report a 36-year-old woman
      who had a hysterectomy for metrorrhagia. Histologic examination showed sarcoid
      granulomas in the endometrium and myometrium. Subsequent examinations revealed
      pulmonary sarcoidosis as well.

PMID- 12206935
TI  - The gynaecological-obstetrical practice of the renaissance physician Amatus
      Lusitanus (Dubrovnik, 1555-1557).
AB  - OBJECTIVE: A gynaecological-obstetrical causation review in Dubrovnik from 1555
      to 1557. Extract from the book "Curationum Medicinalium Centuriae V et VI" Amatus
      Lusitanus. METHOD: A thorough life and work archive study of Amatus Lusitanus has
      been made and, for this review, extracted his gynaecological-obstetrical
      causation observations and annotations. RESULTS: Amatus Lusitanus was an
      undisputed, reputable and respected medical figure during the mid 16th century.
      He decisively focused on intern medicine, incorporating the gynaecological
      obstetrical field. His work and skill, most assuredly, contributed to the better
      comprehension, acknowledgement and reputation of the gynaecological-obstetrical
      practice, thus leaving repute and respect in medical history latitude.
      CONCLUSION: All these cases occurred in Dubrovnik during 1555-1557 and Amatus is
      assuredly an excellent observer and exactist, extracting the "relevant from the
      non-relevant" even in Dubrovnik's gynaecological-obstetrical daily happenings. He
      thoughtfully concludes his inability to remedy a malignant, advanced illness of
      the uterus, presumes an utero-vesico-intestinal fistula and openly speaks of
      medical ineptness of this causation. Proud of his invention in treating
      "contracted nipples"; correct in his advice and recommendations of "long and
      difficult births". Impartial in his perception of puerperal sepsis and its
      unfavourable pathology outcome. His description of "hormone insufficiency" is
      concise and precise; the preferred procedure in an "abortus in tractu" is
      purposeful and meaningful. He closely works with other physicians living and
      working in Dubrovnik; conscientiously directing surgeons in procedures of
      stillborn child births. He explains and treats pyschosexual disturbances "without
      fault" and in concurrence with, not only, the contemporary knowledge of such
      sexual disturbances, but also in concurrence with contemporary psychiatric
      procedures that, even today, are applied in such pathology treatment.

PMID- 12206936
TI  - Term labor and post-term pregnancy can be predicted using fetal fibronectin (fFN)
      and IL-lb concentrations in cervicovaginal secretions of pregnant women.

PMID- 12206938
TI  - Specialist lives: Yldiz Perk.

PMID- 12206939
TI  - Does a pelvic belt influence sacroiliac joint laxity?
AB  - OBJECTIVE: To evaluate the influence of different positions and tensions of a
      pelvic belt on sacroiliac joint laxity in healthy young women. BACKGROUND:
      Clinical experience has shown that positive effects can be obtained with
      different positions and tensions of a pelvic belt. A functional approach to the
      treatment of the unstable pelvic girdle requires an understanding of the effect
      of a pelvic belt on a normal pelvic girdle. METHODS: Sacroiliac joint laxity was
      assessed with Doppler imaging of vibrations. The influence of two different
      positions (low: at the level of the symphysis and high: just below the anterior
      superior iliac spines) and tensions (50 and 100 N) of a pelvic belt was measured
      in ten healthy subjects, in the prone position. Data were analysed using repeated
      measures analysis of variance. RESULTS: Tension does not have a significant
      influence on the amount by which sacroiliac joint laxity with belt differs from
      sacroiliac joint laxity without belt. A significant effect was found for the
      position of the pelvic belt. Mean sacroiliac joint laxity value was 2.2 (SD, 0.2)
      threshold units nearer to the without-belt values when the belt was applied in
      low position as compared to the case with the belt in high position. CONCLUSIONS:
      A pelvic belt is most effective in a high position, while a tension of 100 N does
      not reduce laxity more than 50 N. RELEVANCE: Information about the biomechanical
      effects of a pelvic belt provided by this study will contribute to a better
      understanding of the treatment of women with pregnancy-related pelvic pain.

PMID- 12206940
TI  - Consequences of deltoid muscle elongation on deltoid muscle performance: a
      computerised study.
AB  - BACKGROUND: The deltoid muscle plays an important role in normal shoulder
      function. Knowledge of the position of the glenohumeral rotational centre and of
      the deltoid muscle length is essential to understand optimal placement of a total
      shoulder prosthesis. OBJECTIVE: This study is designed to analyse the effect of
      deltoid muscle elongation on shoulder joint function. DESIGN: A three-dimensional
      model of the glenohumeral joint with deltoid muscle analysis in the scapular
      plane. METHODS: A geometrical three-dimensional ball-and-socket model of the
      shoulder joint was developed. From dry bones, the position of the origins and
      insertions of the three parts of the deltoid muscle relative to the calculated
      centre of rotation of the humeral head was defined. The position and the
      direction of the muscle force working lines relative to this humeral centre were
      calculated using former measurements and CT-data of the deltoid. Muscle length
      tension data were applied to obtain angle-force relationships. The model was used
      to calculate the angle-force relationships, the moment arm and the moment of the
      deltoid muscle components for successive arm elevation angles in the scapular
      plane. These data were compared to those of a theoretical situation assuming a
      10% elongation of the muscle. RESULTS: Muscle angle-force curves show a more
      favourable slope after moderate (10%) deltoid muscle elongation. Elongating the
      muscle by changing the distance between the humeral rotation point and the
      deltoid insertion along the humeral axis does not affect moment arms. The moments
      of the deltoid muscle forces themselves, however, seem more adapted to elevation
      in the scapular plane. The deltoid maximal moment exceeds the arm-weight moment
      by about 40% instead of being approximately equal, and that the maximum is
      situated around 100 degrees of elevation. CONCLUSIONS: From a biomechanical point
      of view, stretching the deltoid muscle by 10% seems to result in a significantly
      more favourable position in case of shoulder elevation at 90 degrees of abduction
      in the scapular plane in a centred glenohumeral joint. RELEVANCE: This model
      suggests that a 10% elongation of the deltoid muscle, the most important shoulder
      abductor, improves its ability to elevate the arm. If properly implemented, this
      observation can be very important in the treatment and early rehabilitation of
      rotator-cuff-insufficient shoulders treated by a specific total shoulder
      replacement design.

PMID- 12206941
TI  - Three-dimensional carpal kinematics in vivo.
AB  - OBJECTIVE: The purpose of this study was to accurately quantify three-dimensional
      in vivo kinematics of all carpal bones in flexion and extension and radial and
      ulnar deviation. DESIGN AND METHODS: The right wrists of 11 healthy volunteers
      were imaged by spiral CT with rotational increments of 5 degrees during ulnar
      radial deviation and of five of them also during flexion-extension motion. One
      regular-dose scan was used and the subsequent scans during wrist motion were
      performed with one-tenth of the regular dose. A three-dimensional matching
      technique using the internal structure of the bones was developed to trace the
      relative translations and rotations of the carpal bones very accurately. RESULTS:
      Most of our results are in concordance with previously published in vitro data.
      We could, among others, substantiate proof to the statement that there is more
      than one kinematic pattern of the scaphoid. Furthermore, we could accurately
      describe small adaptive intercarpal motions in vivo of the distal carpal row.
      CONCLUSIONS: To our knowledge, this is the first time the three-dimensional in
      vivo kinematics of all eight carpal bones is quantified accurately and non
      invasively. RELEVANCE: Kinematics of an injured wrist can be compared to these
      reference data. It may become possible that in this way a ligament lesion can be
      detected with high specificity and sensitivity, and that no other diagnostic
      modality will be needed. With these data we made animations with which the
      complex movements of the bones during different motions of the wrist can be
      viewed. In the future it may become possible that this analysis provides valuable
      information on the long-term results of operative interventions and possibly
      predicts results of operative techniques.

PMID- 12206942
TI  - Grip forces of the fingertips.
AB  - OBJECTIVE: A model has been developed for the power grip on a cylindrical handle.
      The model gives estimates of the forces acting on the fingertips as functions of
      total grip force, diameter of the handle, and hand size. DESIGN: The data in the
      literature were used to estimate the parameters of the model. An experiment was
      conducted to verify that the distribution of the forces is independent of the
      force level. BACKGROUND: In the authors' opinion, the outcomes of the various
      experiments described in the literature can be represented in a compact model
      without too much information loss. METHODS: The forces acting on the fingertips
      of 10 subjects were measured with three different handle diameters and five grip
      force levels. RESULTS: The force sharing turned out to be independent of the grip
      force and the diameter of the handle. CONCLUSIONS: It is advantageous to shape
      the handle so that the local diameters at the fingers are proportional to the
      finger lengths. RELEVANCE: Knowing the force distribution of the power grip is
      important in design of handles. Experimental data presented in a concise form is
      needed also in the development of biomechanical models.

PMID- 12206943
TI  - Analysis of the shape of the tibial tray in total knee arthroplasty using a three
      dimension finite element model.
AB  - OBJECTIVE AND DESIGN: The purpose of this study was to evaluate whether the
      stress and displacement change with differing shapes of the tibial component in
      total knee arthroplasty. BACKGROUND: There are few reports on tibial tray
      mechanics with and without a posterior concave slot, using three-dimensional
      finite element analysis. METHODS: By considering two different shapes for the
      tibial component, we analyzed the von Mises stresses and displacements at the
      component/bone interface and surrounding bone using a three-dimensional finite
      element model. RESULTS: There was no difference between the two designs in
      regards to the von Mises stress fields or displacements. The displacement of the
      tibial tray with a posterior concave slot was less than that of the tray without
      one in some of the loading configurations. The posterior concave slot appears to
      reduce the micromotion of the tibial component. DISCUSSION AND CONCLUSION:
      Overall, this finite element analysis showed little difference between the two
      different types of tibial base plates used with both posterior cruciate ligament
      retention and substitution. The results of this finite element model analysis do
      not support the use of tibial base plates without a posterior cut-out slot.

PMID- 12206944
TI  - Comprehensive testing of 10 different ankle braces. Evaluation of passive and
      rapidly induced stability in subjects with chronic ankle instability.
AB  - OBJECTIVE: The aim of the present investigation was to test the stability of 10
      different ankle braces under passive and rapidly induced loading conditions in a
      population suffering from chronic ankle instability in order to provide objective
      information to choose or recommend an appropriate model for specific needs. In
      addition, the relationship between passive and rapidly induced testing of the
      stabilizing effect against inversion was evaluated to identify if passive support
      characteristics of braces are reflected under rapidly induced conditions. DESIGN:
      An experimental in vivo study with a repeated-measures design was used.
      BACKGROUND: Ankle braces are commonly used for treatment, rehabilitation, and
      prevention of ankle injuries. A variety of products exists but there is few
      information available to assist clinicians, physiotherapists and coaches as well
      as consumers in choosing a brace on a basis of objective information.
      Furthermore, there is a lack of studies that provide data for both passively and
      rapidly induced movement of the ankle joint when using different ankle braces.
      METHODS: Twenty-four subjects with chronic ankle instability participated in the
      project. Passive ankle range of motion measurements were performed in a custom
      built fixture and simulated inversion sprains were elicited on a tilting
      platform. RESULTS: The tested braces restrict range of motion significantly
      compared to the no-brace condition for both the passively and rapidly induced
      inversion and marked differences between braces were revealed. A close
      relationship between passive and rapidly induced test results for inversion was
      found. CONCLUSIONS: Passive as well as rapidly induced stability tests provide a
      basis of objective information to describe the characteristics of different ankle
      braces. Combined results of passive and rapidly induced inversion as well as
      correlation between results demonstrate that passive support characteristics of
      braces are reflected under rapidly induced conditions but the amount of
      restriction is reduced. Therefore, caution should be taken when recommending
      braces for applications under dynamic circumstances only on the basis of passive
      support characteristics. RELEVANCE: A basis of information regarding the
      stability characteristics of different ankle braces under passive and rapidly
      induced conditions will help the clinician and consumer in choosing the most
      appropriate brace model for specific use. The results also provide more insights
      into factors that influence stability characteristics of ankle braces.

PMID- 12206945
TI  - Stiffness and passive peak force changes at the ankle joint: the effect of
      different joint angular velocities.
AB  - OBJECTIVE: To compare peak force and stiffness at the ankle joint in response to
      repetitive dorsiflexion at two joint angular velocities (5 and 25 deg s(-1)).
      DESIGN: Pre- post-repeated measures design. BACKGROUND: Stretching affects the
      biomechanical properties of tissues. In many instances, stretching is performed
      in a cyclic manner. An important factor that might influence the effects of
      stretching is the speed at which the tissues are lengthened. METHODS: Eighteen
      healthy subjects participated. A dynamometer repeatedly moved the ankle joint
      from 0 deg of dorsiflexion to 80% of maximum dorsiflexion over a 2 min period.
      Two joint angular velocities were examined: 5 and 25 deg s(-1). Force and angle
      data were recorded simultaneously. Electromyographic activity from plantar and
      dorsiflexor muscles was monitored. The variables of interest were peak passive
      force and average stiffness at the first and last repetition of motion. RESULTS:
      Peak force was significantly higher (P < 0.05) at 25 deg s(-1) for the first
      repetition. At both joint angular velocities, peak passive force decreased
      significantly over the 2 min of motion. The decreases were 13% and 21% at 5 and
      25 deg s(-1) respectively. Peak passive force was not significantly different (P
      > 0.05) across velocities at 2 min. Stiffness was greater at 25 deg s(-1)
      initially (P < 0.05), however, it decreased significantly across time. The
      magnitude of the decrease was 20% and 31% at 5 and 25 deg s(-1) respectively.
      After 2 min of motion, there was no significant difference (P > 0.05) in
      stiffness across the joint angular velocities examined. CONCLUSION(S): The
      findings showed that while significant differences existed in stiffness and peak
      force across angular velocities at the start of the stretching motion, the
      differences decreased considerably with repeated motion, and were relatively
      similar within 2 min. RELEVANCE: It has long been thought that greater speeds of
      stretch are more likely to lead to muscle injury. Our findings suggest that it is
      most beneficial to stretch at a slow speed initially, thereafter, the speed of
      stretch may be increased.

PMID- 12206946
TI  - Decrease in elbow flexor inhibition after cervical spine manipulation in patients
      with chronic neck pain.
AB  - OBJECTIVE: This study measured functional capacity and subjective pain in
      patients with chronic neck pain before and after manipulation of the cervical
      spine. DESIGN: Outcomes study on 16 patients with chronic neck pain. BACKGROUND:
      Muscle inhibition, i.e., the inability to fully activate a muscle, has been
      observed following joint pathologies and in low back pain conditions. Although
      chronic neck pain has been associated with changes in muscle recruitment and
      coordination in the shoulder and arms, the possibility of muscle inhibition has
      not been explored. METHODS: Biceps activation during a maximal voluntary elbow
      flexor contraction was assessed using the interpolated twitch technique and
      electromyography. Cervical range of motion and pressure pain thresholds were
      measured using a goniometer and an algometer. Manipulation of the cervical spine
      was applied at the level of C5/6/7, and functional assessments were repeated.
      RESULTS: Patients showed significant inhibition in their biceps muscles. Cervical
      range of motion was restricted laterally, and increased pressure pain sensitivity
      was evident. After cervical spine manipulation, a significant reduction in biceps
      inhibition and an increase in biceps force occurred. Cervical range of motion and
      pressure pain thresholds increased significantly. CONCLUSIONS: Significant
      dysfunction in biceps activation was evident in patients with chronic neck pain,
      indicating that this muscle group cannot be used to the full extent. Spinal
      manipulation decreased muscle inhibition and increased elbow flexor strength at
      least in the short term. RELEVANCE: Muscle inhibition in the biceps has not been
      previously documented in patients with chronic neck pain. Further research is
      needed to establish whether muscle inhibition is related to clinical symptoms and
      functional outcome. Spinal manipulation improved muscle function, cervical range
      of motion and pain sensitivity, and might therefore be beneficial for treating
      patients with chronic neck pain.

PMID- 12206947
TI  - Neck muscle strength across the sagittal and coronal planes: an isometric study.
AB  - OBJECTIVE: To determine the maximal isometric strength of neck muscles across
      different anatomical positions in the body sagittal and coronal planes. DESIGN: A
      descriptive study involving maximal isometric strength measurements of the
      cervical musculature in extension, flexion, and left and right lateral bending.
      Before measurements, the new device was tested for reliability. BACKGROUND: The
      literature contains only a few studies on cervical musculature strength
      assessment. Of these, measurement methods have displayed weak reliability. No
      studies existed reporting neck strength at various positions in the body coronal
      plane. METHODS: A new device incorporating local population anthropometry was
      developed for neck strength assessment on an isokinetic dynamometer. The device's
      repeatability attributes at measuring the strength of functionally different
      groups of neck muscles were first evaluated. The isometric apparatus was next
      used to determine the maximal strength of the cervical musculature of 17 healthy
      volunteers at different anatomical positions across the body sagittal and coronal
      motion planes. RESULTS: The results showed good intratester repeatability for
      intraday and day-to-day studies for all measured parameters. Strength values
      demonstrated that extensor muscles yielded the greatest torque and that flexor
      muscles provided the least torque. Linear regression analyses showed strong
      association of isometric strength with anatomical positions in the two body
      planes. CONCLUSIONS: Maximal isometric strength of neck muscles in four
      directions was quantified. Cervical musculature strength levels vary in
      discernible patterns with head-neck positions and contraction directions.
      RELEVANCE: Knowledge of normative values of neck muscle strength is essential for
      designing and implementing appropriate rehabilitation programmes. Results from
      the present study contribute to such literature.

PMID- 12206948
TI  - Does respiration perturb body balance more in chronic low back pain subjects than
      in healthy subjects?
AB  - OBJECTIVE: To determine whether body balance is perturbed more in low back pain
      patients than in healthy subjects, under the concept of posturo-kinetic capacity.
      DESIGN: Comparison of posturographic and respiratory parameters between low back
      pain and healthy subjects. BACKGROUND: It has been demonstrated that respiratory
      movements constitute a perturbation to posture, compensated by movements of the
      spine and of the hips, and that low back pain is frequently associated with a
      loss of back mobility. METHOD: Ten low back pain patients and ten healthy
      subjects performed five posturographic tests under three different respiratory
      rate conditions: quiet breathing (spontaneous), slow breathing (0.1 Hz) and fast
      breathing (0.5 Hz). RESULTS: Intergroup comparison showed that the mean
      displacements of the center of pressure were greater for the low back pain group,
      especially along the antero-posterior axis, where respiratory perturbation is
      primarily exerted. Inter-condition comparison showed that in slow and fast
      breathing relatively to quiet breathing, the mean displacement of the center of
      pressure along the antero-posterior axis was significantly increased only for the
      low back pain group. CONCLUSION: According to the results, respiration presented
      a greater disturbing effect on body balance in low back pain subjects. RELEVANCE:
      This study provides information on the causes of the impaired body balance
      associated with chronic low back pain, which could be used to improve treatment
      strategy.

PMID- 12206949
TI  - Loading response following anterior cruciate ligament reconstruction during the
      parallel squat exercise.
AB  - OBJECTIVE: To determine if individuals 1.5-15 months post-anterior cruciate
      ligament reconstruction demonstrated an equal loading response on their involved
      and uninvolved lower extremity during a parallel squat exercise versus a control
      group. DESIGN: Four-group repeated measures design with one between-subject
      factor (time post-anterior cruciate ligament reconstruction) and two within
      subject factors (knee angle and added weight). BACKGROUND: It has been a clinical
      observation that post-anterior cruciate ligament reconstruction, individuals do
      not place equal amounts of weight upon each lower extremity during double-leg
      exercises. METHODS: Twenty-four subjects were in each of the experimental groups,
      1.5-4 months, 6-7 months, and 12-15 months post-anterior cruciate ligament
      reconstruction, while 24 subjects without history of lower extremity
      pathology/injury served as the control group. Pedar in-shoe sensors were placed
      inside the subjects' shoes to record loading response patterns during the
      exercises. All performed 3 sets of 9 randomized squats to each of the three knee
      flexion angles (30 degrees, 60 degrees, and 90 degrees ) with the three different
      weights (20.45 kg bar only, 35%, and 50% body mass) using a Smith squat rack. A
      three-way repeated measures ANOVA (P < 0.050) was used to compare the differences
      between groups in loading response statically between the uninvolved and involved
      lower extremity for each of the different weights at each knee flexion angle
      during the squat exercise. RESULTS: The three-way repeated measures ANOVA
      revealed that there was a significant group effect (P < 0.001). Thus, the amount
      of time post-anterior cruciate ligament reconstruction affected the difference in
      the subjects' loading response for the uninvolved and involved lower extremities.
      There was also a three-way interaction, indicating that the difference in loading
      response was dependent on the group, amount of knee flexion, and amount of added
      weight (P = 0.010). CONCLUSION: These data suggest that subjects significantly
      load their uninvolved lower extremity until 12-15 months post-anterior cruciate
      ligament reconstruction. RELEVANCE: Based on the results of this study, caution
      may be warranted when adding resistance during the parallel squat for an
      individual's first year post-anterior cruciate ligament reconstruction,
      particularly with less knee flexion to avoid compensation and injury.

PMID- 12206950
TI  - Multidirectional measures of seated postural stability.
AB  - OBJECTIVE: To quantify the limits of stability during a leaning/reaching task and
      determine (1) test-retest reliability and (2) effect of movement direction and
      foot support. DESIGN: Test-retest reliability design. BACKGROUND: Seated reaching
      and leaning are used in rehabilitation programs to assess and train sitting
      balance and motor function. Continuous (as opposed to ordinal), multidirectional
      measures of seated postural stability have not been previously presented.
      METHODS: Twelve older adults performed a seated reaching/leaning task while net
      body centre of pressure displacement and velocity were measured with three
      forceplates (under buttocks and each foot) over two separate days. Conditions of
      movement direction (forward, backward, lateral) and foot support (with and
      without) were randomized. RESULTS: Except for the backward movement in the
      supported foot condition, all measures had moderate to very high reliability.
      Measurements were sensitive to both foot support and movement direction.
      RELEVANCE: Centre of pressure measures provide reliable measures which may be
      useful for clinical assessment of seated postural stability.

PMID- 12206952
TI  - Global Fund dispute in KwaZulu-Natal.

PMID- 12206951
TI  - Who gets smallpox vaccine?

PMID- 12206957
TI  - HIV vaccine optimism in Barcelona.

PMID- 12206960
TI  - Crackdown on persistent infections imminent.

PMID- 12206962
TI  - Scientists join smallpox vaccine controversy.

PMID- 12206965
TI  - Kenya issues new AIDS bill.

PMID- 12206966
TI  - Influenza--WHO cares.

PMID- 12206968
TI  - West Nile virus.
AB  - West Nile (WN) virus is a mosquito-borne flavivirus and human, equine, and avian
      neuropathogen. The virus is indigenous to Africa, Asia, Europe, and Australia,
      and has recently caused large epidemics in Romania, Russia, and Israel. Birds are
      the natural reservoir (amplifying) hosts, and WN virus is maintained in nature in
      a mosquito-bird-mosquito transmission cycle primarily involving Culex sp
      mosquitoes. WN virus was recently introduced to North America, where it was first
      detected in 1999 during an epidemic of meningoencephalitis in New York City.
      During 1999-2002, the virus extended its range throughout much of the eastern
      parts of the USA, and its range within the western hemisphere is expected to
      continue to expand. During 1999-2001, 142 cases of neuroinvasive WN viral disease
      of the central nervous system (including 18 fatalities), and seven cases of
      uncomplicated WN fever were reported in the USA. Most human WN viral infections
      are subclinical but clinical infections can range in severity from uncomplicated
      WN fever to fatal meningoencephalitis; the incidence of severe neuroinvasive
      disease and death increase with age. Serology remains the mainstay of laboratory
      diagnosis. No WN virus-specific treatment or vaccine is available. Prevention
      depends on organised, sustained vector mosquito control, and public education.

PMID- 12206969
TI  - Fluoroquinolone resistance among Gram-positive cocci.
AB  - Resistance to fluoroquinolones among Gram-positive cocci has emerged as these
      antimicrobial agents have become extensively used in clinical medicine.
      Resistance is effected by changes in the bacterial target enzymes DNA gyrase and
      topoisomerase IV, which reduce drug binding, and by action of native bacterial
      membrane pumps that remove drug from the cell. In both cases, quinolone exposure
      selects for spontaneous mutants that are present in large bacterial populations,
      and which contain chromosomal mutations that alter the target protein or increase
      the level of pump expression. Resistance among clinical isolates has been
      greatest in Staphylococcus aureus and particularly among meticillin-resistant
      strains, in which both selection by quinolone exposure and transmission of clonal
      strains in health-care settings have contributed to high prevalence. Resistance
      in Streptococcus pneumoniae has also emerged in the community. Fluoroquinolone
      resistance has arisen in multidrug-resistant clones and its prevalence has been
      especially high in Hong Kong and Spain. Further spread and selection of such
      resistance could compromise the utility of a valuable class of antimicrobial
      agents, a point that emphasises the importance of the careful use of these agents
      in appropriate patients and doses, as well as careful infection-control
      practices.

PMID- 12206970
TI  - Infections and solid organ transplant rejection: a cause-and-effect relationship?
AB  - Although evidence is far from being conclusive, several studies have suggested
      that infections could trigger rejection in different transplant settings. In this
      review we examine the evidence linking cytomegalovirus (CMV), adenovirus,
      enterovirus, parvovirus, and herpes simplex virus infections to the vasculopathy
      leading to cardiac allograft rejection, the association between CMV and chronic
      kidney, lung, and liver graft rejection, and the association of human herpesvirus
      6 reactivation with CMV-related disease in kidney and liver transplant
      recipients. We also review the numerous antiviral prophylactic or pre-emptive
      treatments in use to control CMV infection, and suggest that they do not limit
      immune reactions leading to graft rejection or lower the risk of developing post
      transplantation atherosclerosis in allograft recipients. Finally, we emphasise
      the need for prospective, international studies to clarify the role of infections
      in transplant rejection, to look at virus-to-virus interactions, and to establish
      specific therapeutic strategies. Such strategies must not rely exclusively on
      expensive antiviral agents but also on vaccination or other, innovative
      approaches, such as the use of agents able to inhibit the activity of natural
      killer cells, which might have an important role in acute allograft rejection.

PMID- 12206971
TI  - Antifungal drug resistance to azoles and polyenes.
AB  - There is an increased awareness of the morbidity and mortality associated with
      fungal infections caused by resistant fungi in various groups of patients.
      Epidemiological studies have identified risk factors associated with antifungal
      drug resistance. Selection pressure due to the continuous exposure to azoles
      seems to have an essential role in developing resistance to fluconazole in
      Candida species. Haematological malignancies, especially acute leukaemia with
      severe and prolonged neutropenia, seem to be the main risk factors for acquiring
      deep-seated mycosis caused by resistant filamentous fungi, such us Fusarium
      species, Scedosporium prolificans, and Aspergillus terreus. The still
      unacceptably high mortality rate associated with some resistant mycosis indicates
      that alternatives to existing therapeutic options are needed. Potential measures
      to overcome antifungal resistance ranges from the development of new drugs with
      better antifungal activity to improving current therapeutic strategies with the
      present antifungal agents. Among the new antifungal drugs, inhibitors of beta
      glucan synthesis and second-generation azole and triazole derivatives have
      characteristics that render them potentially suitable agents against some
      resistant fungi. Other strategies including the use of high doses of lipid
      formulations of amphotericin B, combination therapy, and adjunctive immune
      therapy with cytokines are under investigation. In addition, antifungal control
      programmes to prevent extensive and inappropriate use of antifungals may be
      needed.

PMID- 12206972
TI  - Malaria: current status of control, diagnosis, treatment, and a proposed agenda
      for research and development.
AB  - Rolling back malaria is possible. Tools are available but they are not used.
      Several countries deploy, as their national malaria control treatment policy,
      drugs that are no longer effective. New and innovative methods of vector control,
      diagnosis, and treatment should be developed, and work towards development of new
      drugs and a vaccine should receive much greater support. But the pressing need,
      in the face of increasing global mortality and general lack of progress in
      malaria control, is research into the best methods of deploying and using
      existing approaches, particularly insecticide-treated mosquito nets, rapid
      methods of diagnosis, and artemisinin-based combination treatments. Evidence on
      these approaches should provide national governments and international donors
      with the cost-benefit information that would justify much-needed increases in
      global support for appropriate and effective malaria control.

PMID- 12206973
TI  - Kenya rises to infectious diseases challenge.

PMID- 12206974
TI  - Keryn Christiansen, president-elect of the International Society for Infectious
      Diseases. Interviewed by Megan Howe.

PMID- 12206977
TI  - It's a funny new world.

PMID- 12206978
TI  - [Prognostic value of gene expression profiling using cDNA arrays in lymphomas].
AB  - Lymphomas are the most frequent haematological malignancies in France. Their
      histoclinical heterogeneity reflects their complex and combinatorial nature which
      remains poorly elucidated at the molecular level. Today, DNA arrays allow to
      tackle this diversity by measuring the mRNA expression level of thousands of
      genes simultaneously in one sample. Recent publications show the potential of DNA
      arrays to improve the prognostic classification of diffuse large B cell lymphomas
      and of Hodgkin's lymphoma, by identifying new tumour classes unrecognised by
      classical factors.

PMID- 12206979
TI  - [Cured from Hodgkin's disease].
AB  - Hodgkin's disease can be cured from 80 to 90% of cases with a regular improvement
      of therapeutic results since 1960. We detailed the remission criteria with a
      focus on post therapeutic residual masses which did not influence the relapse
      rate. The follow-up of patients in remission is made as an outbasis care every 4
      months during the first year than every 6 months with a routine bilan for 10
      years. Some adverse events can occur with first, the acute leukemia arising
      before 10 years, this risk is decreasing with the disminished use of MOPP
      chemotherapy. The other solid tumors occur later and are related to the patient
      age, the type of treatment given and individual factors. Thyroid diseases are
      frequent but mostly benign needing only consumption of thyroid extracts.
      Fertility is directly related to chemotherapy (including alkylating agents) and
      to pelvic radiation therapy. With the current use of ABVD-type chemotherapy the
      preservation of fertility is good but there is a risk for long term
      cardiopulmonary toxicity almost for the older patients receiving together
      mediastinal radiation therapy. At the end most long-term survivors of Hodgkin's
      disease recover a normal socioprofessional life, while reporting a longer
      duration of fatigue and many children were born after treatments.

PMID- 12206980
TI  - [The detection of sentinel lymph node in nuclear medicine].
AB  - The isotopic detection of the sentinel node is undergoing a fast development in
      breast cancer and melanoma. It requires a good collaboration between a surgeon
      and a nuclear medicine specialist. Although the method is now well defined for
      melanoma, several options remain possible for breast cancer. The injected dose
      and volume can differ between centers, as well as the sites of injection in terms
      of their number, anatomical location and depth. However, since all options seem
      to provide equivalent results, a single intradermal periareolar injection could
      be the preferred choice. The role of imaging remains controversial, but it
      provides a definite complementary information, in particular in case of an
      unusual location of the sentinel node. The addition of dye injection also adds to
      the results. The optimal use of a peroperative hand-held gamma probe requires
      some training for the surgeon. A good selection of the indications is essential
      for a successful detection. Other fields of application are under investigation
      such as colon cancer, head and neck tumors, lung and prostate cancers. By
      avoiding a majority of the routine axillary lymph nodes dissections in small
      breast cancer, the isotopic detection of the sentinel node should dramatically
      decrease the morbidity of axillary staging and the duration of hospital stay for
      the patients.

PMID- 12206981
TI  - [Sentinel lymph nodes in gynecologic cancers].
AB  - The detection of the sentinel lymph node is one of the most significant surgical
      advance in cancer research. This technique allow to decrease the morbidity of a
      surgical gesture which can be noxious in itself even without bringing a profit in
      survival. In the gynaecological cancers the detection of the sentinel lymph node
      is still at the stage of feasibility. An evaluation of the technique and the
      applicability in these cancers is mandatory in view of the prognostic value of
      the nodal involvement in these patients.

PMID- 12206982
TI  - [From cytogenetics to cytogenomics of adipose tissue tumors: 1. Benign adipose
      tissue tumors].
AB  - Benign lipomatous tumors are characterized at the genetic level by different
      types of chromosomal abnormalities. A rearrangement of the HMGIC (HMGA2) gene,
      localized in 12q15 and coding for an architectural non-histone DNA protein, is
      observed in a majority of solitary superficial lipomas. Alterations of HMGIC are
      often resulting from reciprocal translocations, such as t(3;12)(q27-28;q15) that
      fuses LPP with HMGIC, but a variety of chromosomal anomalies, such as deletions,
      inversions or insertions are also observed. Rearrangements of chromosomal regions
      6p21-22, 13q, 11q13, 12q13 or others are described in approximately one third of
      superficial lipoma cases with abnormal karyotypes. The genes involved in these
      alterations remain to be determined. Lipoblastomas are pediatric neoplasms that
      are characterized by rearrangements of PLAG1, located in 8q11-12 whereas
      hibernomas, that resemble brown fat, are associated with 11q13 rearrangements
      together with often complex chromosomal alterations. Deletions of 13q and 16q
      have been identified in spindle cell lipomas. A t(11;16)(q13;p12-13) have been
      described in the two published karyotypes of chondroid lipomas. The chromosomal
      features of other rare benign lipomatous tumors, the differential diagnosis of
      which is occasionally difficult, such as infiltrating intra-muscular lipomas,
      organic deep-seated lipomas, or angiomyolipomas, myolipomas, myxolipomas are
      still poorly defined. Although the genetic characterization of benign lipomatous
      tumors has been dramatically in progress over the last ten years, many aspects
      remain obscure and warrant future investigations for a better comprehension of
      underlying molecular mechanisms.

PMID- 12206983
TI  - [Standards, Options and Recommendations 2000: non metastatic endometrial cancer].
AB  - CONTEXT: The "Standards, Options and Recommendations" (SOR) project, started in
      1993, is a collaboration between the Federation of French Cancer Centers
      (FNCLCC), the 20 French Cancer Centers, and specialists from French Public
      Universities, General Hospitals and Private Clinics, and some specialists learned
      societies. The main objective is the development of clinical practice guidelines
      to improve the quality of health care and the outcome of cancer patients. The
      SORs are developed using a methodology based on a literature review and critical
      appraisal by a multidisciplinary group of experts, with feedback from specialists
      in cancer care delivery. OBJECTIVES: To develop clinical practice guidelines for
      the management of patients with carcinoma of the endometrium according to the
      definitions of the Standards, Options and Recommendations project. METHODS: Data
      were identified by searching Medline , web sites, and using the personal
      reference lists of members of the expert groups. Once the guidelines were
      defined, the document was submitted for review to 63 independent reviewers.
      RESULTS: The main recommendations for the management of carcinoma of the
      endometrium are: 1) The diagnosis of carcinoma of the endometrium is based on
      biopsy and histological examination. However, as first intention, the first
      elements for diagnosis can be obtain from a hysterography, or particularly, a
      endovaginal ultrasound examination. Ultrasound allows locoregional metastases to
      be detected, the CT scan allows the lymph node involvement to be assessed and
      magnetic resonance imaging allows the myometrium invasion to be evaluated. 2) For
      the majority of patients, surgery is the initial treatment, both for localised
      and advanced-stage carcinomas. The excised sample can be used for pathological
      analysis and tumour staging, using the FIGO (Federation internationale de
      gynecologie obstetrique) classification. Surgery for patients with stage I and II
      carcinomas involves total extrafascial hysterectomy with bilateral salpingo
      oophorectomy., In patients with stage III and IV carcinomas radical surgery
      should be performed, when possible. If this is not possible, then surgery should
      be as complete as possible and be associated with a complementary treatment. In
      patients with the most advanced carcinomas, tumour reduction by surgery should be
      performed. 3) Complementary treatment includes external-beam radiotherapy and
      brachytherapy. The decision concerning the extent and type of irradiation should
      be taken taking into consideration the stage and the prognostic factors present.
      For patients with stage I and II carcinoma, complementary treatment with
      brachytherapy can be performed, if the myometrium invasion is not deep, or if the
      carcinoma is grade 2 or 3. Patients with stage III carcinomas can be treated with
      pelvic or abdominal-pelvic complementary irradiation. In patients that cannot
      undergo surgery, exclusive radiotherapy can be performed. 4) In the absence of
      any symptoms, surveillance should include a general clinical and gynaecological
      examination. All patients with symptoms should undergo an additional work-up.

PMID- 12206984
TI  - [Brachial fluoroscopically guided implantation of venous port devices in oncology
      patients].
AB  - Access to the central venous circulation for chemotherapy infusion has
      traditionally been achieved surgically via the subclavian or jugular routes. With
      ongoing improvements in technical management, alternative means of central venous
      access have been developed such as arm-port or forearm-port implantation under
      imaging guidance. Venous arm port devices implantation was attempted in 200
      cancer patients under fluoroscopic guidance, after arm venography. The 4% failure
      rate was due to the inability to perform the arm venogram, venous spasm or
      presence of a large contrast medium hematoma (rolling vein). Median follow-up was
      180 days (range 4-671) and the complication rate was 13.3% (0.7/1,000 patients
      day). Twenty-six complications occurred and were due to venous thrombosis (n =
      3), large brachial hematoma (n = 1), local (n = 7) and systemic sepsis (n = 1),
      skin dehiscence (n = 4), fissuration (n = 4), dislocation (n = 2), obstruction (n
      = 2), and twist of the port (n = 2), leading to a 8.5% removal rate. Main
      indications for arm port implantation may be breast cancer, previous arm or
      cervical venous thrombosis, morbid obesity, respiratory insufficiency, previous
      surgical failure and the irradiated neck.

PMID- 12206985
TI  - [Radiation therapy for chordomas and chondrosarcomas of the base of the skull and
      cervical spine].
AB  - PURPOSE: Prospective analysis of local tumour control, survival and treatment
      complications in 67 consecutive patients treated with fractionated photon and
      proton radiation for a chordoma or a chondrosarcoma of the base of the skull and
      of the cervical spine. PATIENTS AND METHODS: Between December 1995 and January
      2000, 67 patients with a median age of 52.3 years (14-85), were treated using 201
      MeV proton beam of the centre de protontherapie d'Orsay (CPO), 49 for a chordoma
      and 18 for a chondrosarcoma. Irradiation combined high-energy photons and
      protons. Photons represented 2/3 of the total dose and protons 1/3. The median
      total dose delivered within gross tumour volume was 67 Cobalt Gray Equivalent
      (CGE) (60-70). RESULTS: With a mean follow-up of 32 months (4-71), the 3-year
      local control rates were for chordomas and chondrosarcomas of 70.8% and 85.2%,
      respectively and 4-year overall survival rates of 87.7% and 75%, respectively.
      Fourteen tumours (21.5%) failed locally (eight within the gross tumor volume,
      four into the CTV and 2 in an unknown site). Seven patients died of tumour and
      one of intercurrent disease. In univariate analysis, age inferieur ou egal a 52.3
      years (p = 0.002), maximum tumoral diameter < 44.7 mm (p = 0.02) and GTV < 28.4
      mL (0.02), at time of radiotherapy, influenced positively the local control.
      According to multivariate analysis, only age was an independent prognostic factor
      of local control. Only five (7.7%) patients presented grade 3 or 4 complications.
      CONCLUSION: In base of skull chordomas and chondrosarcomas, the combined photon
      and proton therapy offers excellent chances of cure at the price of an acceptable
      toxicity. These results should be confirmed with a longer follow-up.

PMID- 12206986
TI  - [Atypical mesoblastic nephroma: histopathological entity or specific
      anatomoclinical form?].
AB  - Atypical mesoblastic nephroma is a rare kidney tumor mostly which occurred in
      early infancy. We describe two cases of atypical mesoblastic nephroma diagnosed
      in infants aged respectively 2 and 3 months. The tumors were completely removed
      and surgical margins were histologically free of disease. The two patients are
      well 14 and 9 months after surgery. Microscopically, the tumor was characterized
      by a densely cellular proliferation, high mitotic levels, cystic degeneration and
      necrosis. In the literature, the prognostic is good in patients aged fewer than 3
      months and in cases in which the surgical removal was complete.

PMID- 12206987
TI  - [Report on 93rd AACR].

PMID- 12206988
TI  - [Evidence from North-African patients for breast cancer].

PMID- 12206990
TI  - Ara-C- and daunorubicin-induced recruitment of Lyn in sphingomyelinase-enriched
      membrane rafts.
AB  - Induction of apoptosis by DNA-damaging agents such as 1-beta-D
      arabinofuranosylcytosine (Ara-C) includes the activation of Lyn protein tyrosine
      kinase. We have previously established that Ara-C-induced activation of Lyn
      results in its binding to a neutral sphingomyelinase (SMase) and is requisite for
      its stimulation and the induction of apoptosis in U937 cells. However, the spacio
      temporal organization of these events is unclear. This study demonstrates that
      part of the total cellular SMase activity is sequestered in sphingomyelin
      enriched plasma membrane microdomains (rafts). Under Ara-C and daunorubicin (DNR)
      treatment, Lyn is rapidly activated and translocated into rafts. The
      compartmentalization of Lyn (as well as neutral SMase activation and apoptosis)
      induced by these drugs was blocked by the tyrosine kinase inhibitor herbimycin A
      and raft disruption. In conclusion, this study establishes that DNA-damaging
      agents such as Ara-C and DNR rapidly induce Lyn activation and its translocation
      into membrane rafts. This, in turn leads to neutral SMase activation and raft
      associated sphingomyelin hydrolysis with the concomitant generation of the
      proapoptotic lipid second messenger, ceramide. The apparent topological
      partitioning between DNA damage and apoptosis signaling (integrated into
      specialized plasma membrane domains) is discussed.

PMID- 12206991
TI  - Dietary salt intake activates MAP kinases in the rat kidney.
AB  - This study explored the hypothesis that dietary salt promoted changes in renal
      expression of TGF-beta1 and NOS3 by modulating the mitogen-activated protein
      kinase (MAPK) pathways. Sprague-Dawley rats were maintained for four days on
      formulated diets that contained 0.3, 1.0, 3.0, or 8.0% NaCl. An increase in salt
      intake to greater than or equal to 3.0% NaCl increased kinase activities of p38
      MAPK and p42/44 MAPK, but not p46/54 JNK/SAPK, in the cortex and outer and inner
      medulla. Associated with this increased activity was a relative increase in the
      phosphorylated forms of the transcription factors ATF-2 and Elk-1. Compared with
      rats on 0.3% NaCl diet, glomerular preparations from rats on 8.0% NaCl diet
      contained more NOS3 and produced greater amounts of total and active TGF-beta1
      and NOx. PD-098059, a MEK1 inhibitor, and SB-203580, an inhibitor of p38
      MAPKalpha-gamma, diminished NOS3 expression and production of TGF-beta1 and NOx.
      TEA, administered intravenously 5 min before harvesting kidneys of rats on the
      8.0% NaCl diet, decreased activities of both p38 MAPK and p42/44 MAPK, compared
      with vehicle-treated animals. Thus, an increase in dietary salt activated through
      a TEA-sensitive pathway the p38 MAPK and p42/44 MAPK signaling cascades, which
      promoted the increase in glomerular TGF-beta1 and NOS3 expression.

PMID- 12206992
TI  - Transgenic overexpression of the sarcoplasmic reticulum Ca2+ATPase improves
      reticular Ca2+ handling in normal and diabetic rat hearts.
AB  - Slowed relaxation in diabetic cardiomyopathy (CM) is partially related to
      diminished expression of the sarcoplasmic reticulum (SR) Ca2+-ATPase SERCA2a. To
      evaluate the impact of SERCA2a overexpression on SR Ca2+ handling in diabetic CM,
      we 1) generated transgenic rats harboring a human cytomegalovirus
      enhancer/chicken beta-actin promotor-controlled rat SERCA2 transgene (SERCA2
      TGR), 2) characterized their SR phenotype, and 3) examined whether transgene
      expression may rescue SR Ca2+ transport in streptozotocin-induced diabetes. The
      transgene was expressed in all heart chambers. Compared to wild-type (WT) rats, a
      heterozygous line exhibited increased SERCA2 mRNA (1.5-fold), SERCA2 protein
      (+26%) and SR Ca2+ uptake (+37%). Phospholamban expression was not altered. In
      SERCA2-TGR, contraction amplitude (+48%) and rates of contraction (+34%) and
      relaxation (+35%) of isolated papillary muscles (PM) were increased (P2+ uptake
      and SERCA2 protein of SERCA2-TGR were 1.3-fold higher (P2+ uptake, accelerates
      relaxation and compensates, in part, for depressed Ca2+ uptake in diabetic CM.
      Therefore, SERCA2 expression might constitute an important therapeutic target to
      rescue cardiac SR Ca2+ handling in diabetes.

PMID- 12206993
TI  - Fatty acid augmentation of the cardiac slowly activating delayed rectifier
      current (IKs) is conferred by hminK.
AB  - The mechanism by which dietary fatty acids confer protection against cardiac
      arrhythmias and sudden cardiac death is not resolved. Here, we study the effects
      of several known cardio-protective and arrhythmogenic fatty acids on the slowly
      activating delayed rectifier potassium current (IKs), which is responsible for
      the repolarization phase of the cardiac action potential. cRNAs encoding either
      or both of the two subunits, KvLQT1 and hminK, that together produce IKs, were
      injected into Xenopus oocytes, and the effects of various fatty acids were
      determined. Docosahexaenoic acid (DHA) significantly augmented IKs as did the
      short-chained fully saturated lauric acid, and to a lesser extent the cis
      unsaturated oleic acid. Eicosapentaenoic acid (EPA) was without significant
      effect on current magnitude, although it reduced the rate of activation. These
      results suggest that not all "antiarrhythmic" fatty acids target the same
      channel. To examine the role of hminK in this response, KvLQT1 was expressed
      alone. In this case, DHA, lauric acid, and oleic acid did not augment current,
      suggesting that hminK confers fatty acid sensitivity to IKs.

PMID- 12206994
TI  - MEK and ERK inhibitors enhance the anti-proliferative effect of interferon
      alpha2b.
AB  - Interferon (IFN)-alpha, initially characterized as an antiviral cytokine, affects
      several cellular functions. It is used in clinical practice for the treatment of
      several tumors, including hematopoietic malignancies, due to its
      antiproliferative effects. To better characterize the molecular mechanism(s)
      underlying this property, we conducted our studies in purified primary CD4+ T
      cells stimulated with anti-CD3 and interleukin (IL)-2. Upon treatment with IFN
      alpha, the cells were blocked in the G0/G1 phase of the cell cycle and exhibited
      impaired entry into S phase and reduced proliferation. Moreover, we detected
      short- and long-term inhibition of extracellular signal-regulated kinase (ERK)
      and mitogen-activated ERK-regulating kinase (MEK) function, known to control
      cellular proliferation. The activity of the upstream regulators, Ras and Raf-1,
      was not affected. Analysis of downstream events controlled by the MEK/ERK pathway
      showed reduced activity of cyclin-dependent kinase (Cdk)-2 and -4, high levels of
      the mitotic inhibitors, p21Waf1 and p27Kipl, and decreased cyclin D and E
      expression. When IFN-alpha was used in combination with MEK and ERK inhibitors,
      we observed a dose-dependent additive effect in reducing cellular proliferation.
      Our data demonstrate that IFN-alpha may be associated with other molecules to
      inhibit cellular growth by targeting the MEK/ERK pathway. This may eventually
      lead to new clinical strategies to strengthen its anticancer effect.

PMID- 12206995
TI  - The PDZ scaffold protein INAD abolishes apparent store-dependent regulation of
      the light-activated cation channel TRP.
AB  - In fly photoreceptor cells, light initiates a G protein-coupled phospholipase Cb
      dependent signaling cascade that results in the depolarization of the cell
      membrane, which is mediated by the cation channels TRP and TRPL. Together with
      phospholipase Cb and an eye-specific protein kinase C, TRP is tethered to the
      scaffolding protein INAD, which forms a multimolecular signaling complex.
      Divergent data from expressed TRP and studies from photoreceptor cells have
      brought up a controversy whether or not a capacitative calcium entry (CCE)
      mechanism is involved in the Drosophila phototransduction pathway. Our initial
      characterization of TRP from photoreceptors of Calliphora vicina supported the
      hypothesis of a CCE mechanism, as heterologously expressed TRP was stimulated
      after application of thapsigargin. The situation changed when the PDZ domain
      protein INAD was coexpressed with TRP. In cells coexpressing TRP and INAD, no
      calcium entry was detectable on application of store depletion protocols.
      Suppression of CCE by INAD was not observed when the described interaction was
      disrupted by mutations in TRP and INAD. Our data show that apparent activation of
      TRP by CCE is abolished by INAD. Within the complex, the proteins necessary for
      phototransduction mutually influence their activities. The results support the
      hypothesis of a store-independent activation of TRP.

PMID- 12206996
TI  - Involvement of MAP kinase in the regulation of amyloid precursor protein
      processing by novel cholinesterase inhibitors derived from rasagiline.
AB  - Two novel neuroprotective cholinesterase (ChE) inhibitors, TV3326, (N-propargyl
      (3R) aminoindan-5-yl)-ethyl methyl carbamate, and TV3279, (N-propargyl-(3S)
      aminoindan-5-yl)-ethyl methyl carbamate, were derived from rasagiline for the
      treatment of Alzheimer's disease (AD). TV3326 also inhibits monoamine oxidase
      (MAO)-A and -B, whereas its S-isomer, TV3279, lacks MAO inhibitory activity. The
      action of these drugs in the regulation of amyloid precursor protein (APP)
      processing, using rat PC12 and human SH-SY5Y neuroblastoma cells, was examined.
      Both isomers stimulated the release of the non-amyloidogenic a-secretase form of
      soluble APP (sAPPalpha) from these cell lines. The increases in sAPPalpha,
      induced by TV3326 and TV3279, were dose-dependent (0.1-100 mM) and blocked by the
      hydroxamic acid-based metalloprotease inhibitor, Ro31-9790, suggesting mediation
      via a-secretase activity. Using several signal transduction inhibitors, we
      identified the involvement of protein kinase C (PKC), mitogen-activated protein
      (MAP) kinase, and tyrosine kinase-dependent pathways in the enhancement of
      sAPPalpha release by TV3326 and TV3279. In addition, both drugs directly induced
      the phosphorylation of p44 and p42 MAP kinase, which was abolished by the
      specific inhibitors of MAP kinase activation, PD98059 and U0126. These data
      suggest a novel pharmacological mechanism whereby these ChE inhibitors regulate
      the secretory processes of APP via activation of the MAP kinase pathway.

PMID- 12206997
TI  - Etomoxir-induced increase in UCP3 supports a role of uncoupling protein 3 as a
      mitochondrial fatty acid anion exporter.
AB  - The physiological function of human uncoupling protein-3 is still unknown.
      Uncoupling protein-3 is increased during fasting and high-fat feeding. In these
      situations the availability of fatty acids to the mitochondria exceeds the
      capacity to metabolize fatty acids, suggesting a role for uncoupling protein-3 in
      handling of non-metabolizable fatty acids. To test the hypothesis that uncoupling
      protein-3 acts as a mitochondrial exporter of non-metabolizable fatty acids from
      the mitochondrial matrix, we gave human subjects Etomoxir (which blocks
      mitochondrial entry of fatty acids) or placebo in a cross-over design during a 36
      h stay in a respiration chamber. Etomoxir inhibited 24-h fat oxidation and fat
      oxidation during exercise by approximately 14-19%. Surprisingly, uncoupling
      protein-3 content in human vastus lateralis muscle was markedly up-regulated
      within 36 h of Etomoxir administration. Up-regulation of uncoupling protein-3 was
      accompanied by lowered fasting blood glucose and increased translocation of
      glucose transporter-4. These data support the hypothesis that the physiological
      function of uncoupling protein-3 is to facilitate the outward transport of non
      metabolizable fatty acids from the mitochondrial matrix and thus prevents
      mitochondria from the potential deleterious effects of high fatty acid levels. In
      addition our data show that up-regulation of uncoupling protein-3 can be
      beneficial in the treatment of type 2 diabetes.

PMID- 12206998
TI  - Function of beta-amyloid in cholesterol transport: a lead to neurotoxicity.
AB  - Amyloid beta-peptide (Abeta), Abeta precursor protein (APP), apolipoprotein E
      (apoE), and elevated cholesterol levels have been linked to Alzheimer's disease
      (AD) pathology. High cholesterol levels increase APP and apoE expression in human
      NT2 neuron progenitor cells. A cholesterol-rich environment also induces
      processing of APP, leading to the formation of Abeta and Abeta peptide fragments.
      Using a novel method, we determined that 1) cholesterol binds to Abeta at alpha
      secretase cleavage site; 2) Abeta17-40 rather than Abeta1-40 prevents cholesterol
      from binding to apoE; 3) Abeta1-40 inhibits cholesterol from binding to low
      density lipoprotein (LDL), leading to decrease cholesterol influx and
      intracellular cholesterol levels; 4) the binding of cholesterol to apoE or LDL
      was abolished completely in presence of Abeta1-42. Increased extracellular free
      cholesterol levels are toxic to neurons; this toxicity is prevented by specific
      lipoproteins, such as high-density lipoproteins, which maintain their ability to
      bind cholesterol in the presence of Abeta. We propose that one of the
      physiological functions of Abeta and APP is to control cholesterol transport. AD
      is associated with increased Abeta production. High cholesterol levels also lead
      to overproduction of Abeta. Abeta blocks cholesterol trafficking and changes
      cholesterol homeostasis leading to neurodegeneration and the onset and/or
      progression of AD pathology.

PMID- 12206999
TI  - Augmentation of cardiac contractility with no change in L-type Ca2+ current in
      transgenic mice with a cardiac-directed expression of the human adenylyl cyclase
      type 8 (AC8).
AB  - The beta-adrenergic cascade is severely impaired in heart failure (HF), in part
      because of a reduction in the activity of the two dominant cardiac adenylyl
      cyclase (AC) isoforms, AC5 and AC6. Hence, cardiac-directed AC overexpression is
      a conceivable therapeutic strategy in HF. In this study, we explored the
      consequences at the cellular and organ level of a cardiac-directed expression of
      the human AC8 in the transgenic mouse line AC8TG. Unlike AC5 and AC6, which are
      inhibited by intracellular Ca2+, AC8 is stimulated by Ca2+-calmodulin.
      Langendorff perfused hearts from AC8TG mice had a twofold higher left ventricular
      systolic pressure, a 40% faster heart rate, a 37% faster relaxation, and a 30%
      higher sensitivity to external Ca2+ than nontransgenic control mice (NTG). Cell
      shortening measured in isolated ventricular myocytes developed 22% faster and
      relaxed 43% faster in AC8TG than in NTG mice. Likewise, Ca2+ transients measured
      in fluo-3 AM-loaded myocytes were 30% higher and relaxed 24% faster in AC8TG
      compared with NTG mice. In spite of the large increase in Ca2+ transients and
      contraction, expression of AC8 had no effect on the whole-cell L-type Ca2+
      current (ICa, L) amplitude. Moreover, ICa, L was unchanged even when AC8 was
      activated by raising intracellular Ca2+. Thus, cardiac expression of AC8 leads to
      an increase in cAMP that activates specifically Ca2+ uptake into the sarcoplasmic
      reticulum but not Ca2+ influx at the sarcolemma, suggesting a strong
      compartmentation of the cAMP signal.

PMID- 12207000
TI  - Low doses of the endocrine disruptor bisphenol-A and the native hormone 17beta
      estradiol rapidly activate transcription factor CREB.
AB  - Endocrine-disrupting chemicals (EDCs) are hormone-like agents present in the
      environment that alter the endocrine system of wildlife and humans. Most EDCs
      have potencies far below those of the natural hormone 17beta-E2 when acting
      through the classic estrogen receptors (ERs). Here, we show that the
      environmental estrogen Bisphenol-A and the native hormone 17beta-E2 activate the
      transcription factor, cAMP-responsive element binding protein (CREB) with the
      same potency. Phosphorylated CREB (P-CREB) was increased after only a 5-minute
      application of either BPA or 17beta-E2 in a calcium-dependent manner. The effect
      was reproduced by the membrane-impermeable molecule E2 conjugated to horseradish
      peroxidase (E-HRP). The increase in P-CREB was not modified by the anti-estrogen
      ICI 182,780. Therefore, low-dose of BPA activates the transcription factor CREB
      via an alternative mechanism, involving a non-classical membrane estrogen
      receptor. Because these effects are elicited at concentrations as low as 10(-9)
      M, this observation is of environmental and public health relevance.

PMID- 12207001
TI  - Hypoxic pulmonary artery fibroblasts trigger proliferation of vascular smooth
      muscle cells: role of hypoxia-inducible transcription factors.
AB  - Chronic lung hypoxia causes vascular remodeling with pulmonary artery smooth
      muscle cell (SMCPA) hyperplasia, resulting in pulmonary hypertension and cor
      pulmonale. We investigated SMCPA and pulmonary artery adventitial fibroblasts
      (FBPA) for their proliferative response to hypoxia. Strong SMCPA growth occurred
      under hypoxic conditions in SMCPA/FBPA co-cultures, but not in SMCPA
      monocultures. SMCPA growth was fully reproduced by transferring serum-free
      supernatant from hypoxic cultured FBPA to normoxic SMCPA. Hypoxia-inducible
      transcription-factor subtypes (HIF-1alpha, HIF-2alpha, HIF-3alpha) and its
      dependent target genes, carrying the hypoxia-responsive-element as regulatory
      component, were strongly activated in both hypoxic FBPA and SMCPA. HIF
      transcription-factor decoy technique, employed to FBPA during hypoxic culturing,
      blocked the mitogenic activity of FBPA conditioned medium on SMCPA. The data
      suggest that hypoxia-driven gene regulation in pulmonary artery fibroblasts
      results in a mitogenic stimulus on adjacent pulmonary artery smooth muscle cells,
      and HIF-transcription-decoy may offer a new therapeutic approach to suppress
      these events.

PMID- 12207002
TI  - Crystal structures of leukotriene A4 hydrolase in complex with captopril and two
      competitive tight-binding inhibitors.
AB  - Leukotriene (LT) A4 hydrolase/aminopeptidase is a bifunctional zinc enzyme that
      catalyzes the final step in the biosynthesis of LTB4, a potent chemoattractant
      and immune modulating lipid mediator. Here, we report a high-resolution crystal
      structure of LTA4 hydrolase in complex with captopril, a classical inhibitor of
      the zinc peptidase angiotensin-converting enzyme. Captopril makes few
      interactions with the protein, but its free thiol group is bound to the zinc,
      apparently accounting for most of its inhibitory action on LTA4 hydrolase. In
      addition, we have determined the structures of LTA4 hydrolase in complex with two
      selective tight-binding inhibitors, a thioamine and a hydroxamic acid. Their
      common benzyloxyphenyl tail, designed to mimic the carbon backbone of LTA4, binds
      into a narrow hydrophobic cavity in the protein. The free hydroxyl group of the
      hydroxamic acid makes a suboptimal, monodentate complex with the zinc, and
      strategies for improved inhibitor design can be deduced from the structure. Taken
      together, the three crystal structures provide the molecular basis for the
      divergent pharmacological profiles of LTA4 hydrolase inhibitors. Moreover, they
      help define the binding pocket for the fatty acid-derived epoxide LTA4 as well as
      the subsites for a tripeptide substrate, which in turn have important
      implications for the molecular mechanisms of enzyme catalyses.

PMID- 12207003
TI  - The relationship of hepatic tissue oxygenation with nitric oxide metabolism in
      ischemic preconditioning of the liver.
AB  - Ischemic preconditioning (IPC) may increase the hepatic tolerance of ischemic
      injury during liver surgery and transplantation via nitric oxide (NO) formation.
      This study investigates the effect of IPC on hepatic tissue oxygenation and the
      role of NO stimulation and inhibition on the preconditioning effect in the rat
      liver. Study groups had 1) sham laparotomy; 2) 45-min lobar liver ischemia and 2
      h reperfusion (IR); 3) IPC with 5-min ischemia and 10-min reperfusion before IR;
      4) L-arginine before IR; and 5) Nw-Nitro-L-arginine methyl ester (L-NAME) + IPC
      before IR. Hepatic tissue oxygenation was monitored by near-infrared
      spectroscopy. Plasma alanine aminotransferase and plasma nitrite/nitrate were
      measured. Following IR there was significant decrease in oxyhemoglobin and
      cytochrome oxidase and an increase in deoxyhemoglobin (PA redox state, PL
      arginine did not attenuate the impairment in hepatic tissue oxygenation after IR
      (P>0.05 vs IR). In contrast, inhibition of NO synthesis blocked the effect of IPC
      and further impaired tissue oxygenation (decreased cytochrome oxidase CuA redox
      state and increased deoxyhemoglobin, both PL-arginine and increased by NO
      blockade with L-NAME (Plasma ALT, all P< 0.05 vs IR). Hepatic tissue oxygenation
      correlated significantly with ALT and plasma nitrite/nitrate. Ischemic
      preconditioning significantly improved hepatic intra cellular oxygenation and
      reduced hepatocellular injury. NO stimulation reduced hepatocellular injury,
      whereas inhibition of nitric oxide synthesis blocked the effect of IPC and
      reduced tissue oxygenation and increased hepatocellular injury.

PMID- 12207004
TI  - The role of caspases in cryoinjury: caspase inhibition strongly improves the
      recovery of cryopreserved hematopoietic and other cells.
AB  - Cryopreserved cells and tissues are increasingly used for stem cell
      transplantation and tissue engineering. However, their freezing, storage, and
      thawing is associated with severe damage, suggesting the need for better
      cryopreservation methods. Here, we show that activation of caspase-3 is induced
      during the freeze-thaw process. Moreover, we demonstrate that prevention of
      caspase activation by the caspase inhibitor zVAD-fmk strongly improves the
      recovery and survival of several cryopreserved cell types and hematopoietic
      progenitor cells. A short preincubation with the caspase inhibitor after thawing
      also enhances the colony-forming activity of hematopoietic progenitor cells up to
      threefold. Furthermore, overexpression of Bcl-2, but not the blockade of the
      death receptor signaling, confers protection, indicating that cryoinjury
      associated cell death is mediated by a Bcl-2-controlled mitochondrial pathway.
      Thus, our data suggest the use of zVAD-fmk as an efficient cryoprotective agent.
      The addition of caspase inhibitors may be an important tool for the
      cryopreservation of living cells and advantageous in cell transplantation, tissue
      engineering, and other genetic technologies.

PMID- 12207005
TI  - Codon 12 and codon 13 mutations at the K-ras gene induce different soft tissue
      sarcoma types in nude mice.
AB  - K-ras codon 12 mutation is more oncogenic in in vitro and in vivo experimental
      systems than K-ras codon 13 mutation. Moreover, human colorectal tumors bearing a
      codon 12 mutation are more aggressive, invasive, and metastatic than the same
      tumor types carrying a codon 13 mutation. However, despite the association
      between specific sarcoma types and codon 12 or codon 13 mutations, the
      relationship between the position of the mutated codon at ras genes and tumor
      aggressiveness has not been studied in this tumor type. Here, we used a nude mice
      model to evaluate the tumorogenic capacity of stable transfectants of NIH3T3
      fibroblasts, expressing K-ras mutated at codon 12 (K12) or 13 (K13), and
      morphologically, functionally, and molecularly compared these tumors. We found
      histopathological differences between them, K12-derived tumors showing
      fibrosarcoma-like features, whereas K13-derived tumors resembled malignant
      fibrous histiocytomas. Moreover, K12 tumors showed shorter latency of appearance,
      lower apoptotic and mitotic rates, and higher expression of markers for sarcoma
      aggressiveness (Ki67, p53 and c-myc) than K13 tumors. They also showed
      differences in the expression or activation of Ras, Ras downstream pathways [c
      Jun N-terminal kinase (JNK), MAPK and AKT], and apoptotic [AKT, Bcl-2, Focal
      adhesion kinase (FAK)] and mitotic (cyclin B1) regulators, which could explain
      their functional differences. Most remarkably, the significantly diminished
      apoptotic rate observed in K12-derived tumors was associated with enhanced
      antiapoptotic signaling through the AKT pathway. These morphological, functional,
      and molecular differences demonstrate that codon 12 and codon 13 mutations in the
      K-ras oncogene can induce two different soft tissue sarcoma types in our in vivo
      model.

PMID- 12207007
TI  - SAGE transcript profiles of normal primary human hepatocytes expressing oncogenic
      hepatitis B virus X protein.
AB  - Hepatitis B virus (HBV) is a major risk factor for hepatocellular carcinoma
      (HCC). HBV encodes an oncogenic HBx gene that functions as a transcriptional
      coactivator of multiple cellular genes. To understand the role(s) of HBx in the
      early genesis of HCC, we systematically analyzed gene expression profiles by
      serial analysis of gene expression (SAGE) in freshly isolated human primary
      hepatocytes infected with a replication-defective adenovirus containing HBx. A
      total of 19,501 sequence tags (representing 1443 unique transcripts) were
      analyzed, which provide a distribution of a transcriptome characteristic of
      normal hepatocytes and a profile associated with HBx expression. Examples of the
      targeted genes were confirmed by the Megarray analysis with a significant
      correlation between quantitative SAGE and Megarray (r = 0.8, P < 0.005). In HBx
      expressing hepatocytes, a total of 57 transcripts (3.9%) were induced, and 46
      transcripts (3.3%) were repressed by more than fivefold. Interestingly, most of
      the HBx-up-regulated transcripts can be clustered into three major classes,
      including genes that encode ribosomal proteins, transcription factors with zinc
      finger motifs, and proteins associated with protein degradation pathways. These
      results suggest that HBx may function as a major regulator in common cellular
      pathways that, in turn, regulate protein synthesis, gene transcription, and
      protein degradation.

PMID- 12207006
TI  - Cyclosporin A blocks muscle differentiation by inducing oxidative stress and
      inhibiting the peptidyl-prolyl-cis-trans isomerase activity of cyclophilin A:
      cyclophilin A protects myoblasts from cyclosporin A-induced cytotoxicity.
AB  - Allogenic myoblast transplantation (AMT) is under investigation for treatment of
      severe genetic myopathies. Data regarding the role of cyclosporine (CsA) and FK
      506 in AMT have shown that CsA is less effective than FK-506. For this study, we
      investigated mechanisms of CsA toxicity during AMT and showed that a high level
      of reactive oxygen species (ROS) generated by CsA, mediated partly by inhibition
      of the peptidylprolyl-cis-trans-isomerase (PPIase)-like activity of cyclophilin A
      (CypA), blocked differentiation and induced apoptosis at an early stage of muscle
      differentiation. Inhibition of the PPIase-like activity of CypA alone also
      blocked muscle differentiation. However, CsA toxicity did not depend on the
      inhibition of calcineurin activity during muscle differentiation. Together, these
      data suggest that CsA-mediated inhibition of the PPIase-like activity of CypA and
      the high level of ROS generation contributed to the low efficacy of CsA in AMT.
      In addition, we showed that a reduction of oxidative stress protected cells from
      CsA-induced apoptosis, and myoblasts that had survived after preexposure to CsA
      not only proliferated and differentiated reversibly but also gained resistance to
      subsequent CsA exposure. Thus, administration of antioxidants or overexpression
      of CypA either exogenously or endogenously during CsA treatment has the potential
      to improve the success of this treatment in AMT.

PMID- 12207008
TI  - Bioreactors mediate the effectiveness of tissue engineering scaffolds.
AB  - We hypothesized that the mechanically active environment present in rotating
      bioreactors mediates the effectiveness of three-dimensional (3D) scaffolds for
      cartilage tissue engineering. Cartilaginous constructs were engineered by using
      bovine calf chondrocytes in conjunction with two scaffold materials (SM)
      (benzylated hyaluronan and polyglycolic acid); three scaffold structures (SS)
      (sponge, non-woven mesh, and composite woven/non-woven mesh); and two culture
      systems (CS) (a bioreactor system and petri dishes). Construct size, composition
      [cells, glycosaminoglycans (GAG), total collagen, and type-specific collagen mRNA
      expression and protein levels], and mechanical function (compressive modulus)
      were assessed, and individual and interactive effects of model system parameters
      (SM, SS, CS, SM*CS and SS*CS) were demonstrated. The CS affected cell seeding
      (higher yields of more spatially uniform cells were obtained in bioreactor-grown
      than dish-grown 3-day constructs) and subsequently affected chondrogenesis
      (higher cell numbers, wet weights, wet weight GAG fractions, and collagen type II
      levels were obtained in bioreactor-grown than dish-grown 1-month constructs). In
      bioreactors, mesh-based scaffolds yielded 1-month constructs with lower type I
      collagen levels and four-fold higher compressive moduli than corresponding sponge
      based scaffolds. The data imply that interactions between bioreactors and 3D
      tissue engineering scaffolds can be utilized to improve the structure, function,
      and molecular properties of in vitro-generated cartilage.

PMID- 12207009
TI  - The alpha-like RNA polymerase II core subunit 3 (RPB3) is involved in tissue
      specific transcription and muscle differentiation via interaction with the
      myogenic factor myogenin.
AB  - RNA polymerase II core subunit 3 (RPB3) is an a-like core subunit of RNA
      polymerase II (pol II). It is selectively down-regulated upon treatment with
      doxorubicin (dox). Due to the failure of skeletal muscle cells to differentiate
      when exposed to dox, we hypothesized that RPB3 is involved in muscle
      differentiation. To this end, we have isolated human muscle RPB3-interacting
      proteins by using yeast two-hybrid screening. It is of interest that an
      interaction between RPB3 and the myogenic transcription factor myogenin was
      identified. This interaction involves a specific region of RPB3 protein that is
      not homologous to the prokaryotic a subunit. Although RPB3 contacts the basic
      helix-loop-helix (HLH) region of myogenin, it does not bind other HLH myogenic
      factors such as MyoD, Myf5, and MRF4. Coimmunoprecipitation experiments indicate
      that myogenin contacts the pol II complex and that the RPB3 subunit is
      responsible for this interaction. We show that RPB3 expression is regulated
      during muscle differentiation. Exogenous expression of RPB3 slightly promotes
      myogenin transactivation activity and muscle differentiation, whereas the region
      of RPB3 that contacts myogenin, when used as a dominant negative molecule (Sud),
      counteracts these effects. These results indicate for the first time that the
      RPB3 pol II subunit is involved in the regulation of tissue-specific
      transcription.

PMID- 12207010
TI  - Physiological role of tumor necrosis factor alpha in traumatic muscle injury.
AB  - degenerative and regenerative roles of tumor necrosis factor alpha (TNF-alpha), a
      pro-inflammatory cytokine with pleiotropic functions, were investigated by using
      TNF receptor 1 and 2 double knockout (TNFR-DKO) and TNF-alpha antibody
      neutralized mice following traumatic freeze injury to the tibialis anterior
      muscle. In wild-type control mice, TNF-alpha mRNA transcripts and protein
      increased following injury and gradually returned to control (uninjured) levels
      by 13 days. A reduction in MyoD mRNA expression occurred in TNF-alpha-deficient
      mice, although there were no visible differences in MyoD immunostaining or
      histological characteristics in regenerating muscles. At 5 days post-injury, the
      reductions in isometric strength in TNFR-DKO and TNF-alpha-depleted mice did not
      differ from that of wild-type mice but by 13 days after injury, the TNFR-DKO and
      TNF-alpha-depleted mice exhibited strength deficits twice that of wild-type mice
      (i.e., 27-31% vs 13%). Muscle injury was also accompanied by increased expression
      of interleukin-6 (IL-6), but IL-6-deficient mice demonstrated MyoD expression and
      recovery of isometric strength similar to that of wild-type mice. These data
      indicate that TNF-alpha is involved in the recovery of muscle function after
      traumatic muscle injury, and this effect might be associated with modulation of
      muscle regulatory genes, including MyoD.

PMID- 12207011
TI  - NCX-4016, a nitric oxide-releasing aspirin, protects endothelial cells against
      apoptosis by modulating mitochondrial function.
AB  - We investigated the effect of a nitric oxide (NO)-releasing derivative of aspirin
      (NCX-4016) on a mitochondria-dependent model of apoptosis in human umbilical
      endothelial cells (HUVEC). Exposure of HUVEC to staurosporine caused a
      progressive fall in mitochondrial membrane potential (DeltaPsi(m)) and apoptosis.
      Exposure to an NO donor, (z)-1-[2-(2-aminoethyl)-N-(2-ammonioethyl)amino]diazen-1
      ium-1,2-diolate (DETA-NO), caused an early (1-3h) hyperpolarization of
      DeltaPsi(m) and reduction of apoptosis that was followed (at 4-8 h) by an
      accelerated collapse of DeltaPsi(m) and cell death. In contrast, treatment with
      NCX-4016, but not with aspirin or a non-NO-releasing analogue of NCX-4016,
      protected HUVEC against the apoptotic actions of staurosporine for up to 8 h.
      Confocal microscopy demonstrated that although NCX-4016 released NO in
      subcellular compartments, DETA-NO caused a generalized increase in cytosolic
      fluorescence. Exposure to DETA-NO resulted in a rapid and profound inhibition of
      cell respiration (78.3 +/- 6.4%), whereas NCX-4016 caused a less pronounced
      reduction in oxygen consumption (43.5 +/- 5.3%). Staurosporine caused a time
      dependent activation of proapoptotic caspases. NCX-4016 prevented this
      activation, whereas DETA-NO failed to inhibit caspase activity. In contrast to
      DETA-NO, NCX-4016 did not increase mitochondrial oxidative stress. These data
      demonstrated that NCX-4016 conveys NO directly inside endothelial cells and
      modulates mitochondrial function.

PMID- 12207012
TI  - The HIV-1 Nef protein and phagocyte NADPH oxidase activation.
AB  - Nef, a multifunctional HIV protein, activates the Vav/Rac/p21-activated kinase
      (PAK) signaling pathway. Given the potential role of this pathway in the
      activation of the phagocyte NADPH oxidase, we have investigated the effect of the
      HIV-1 Nef protein on the phagocyte respiratory burst. Microglia (cell line and
      primary culture) were transduced with lentiviral expression vectors. Expression
      of Nef did not activate the NADPH oxidase by itself but led to a massive
      enhancement of the responses to a variety of stimuli (Ca(2+) ionophore, formyl
      peptide, endotoxin). These effects were not caused by up-regulation of phagocyte
      NADPH oxidase subunits. Nef mutants lacking motifs involved in the interaction
      with Vav and PAK failed to reproduce the effects of wild type Nef, suggesting a
      role for the Vav/Rac/PAK signaling pathway. The following results suggest a key
      role for Rac in the priming effect of Nef. (i) Inactivation of Rac by Clostridium
      difficile toxin B abolished the Nef effect. (ii) The fraction of activated Rac1
      was increased in Nef-transduced cells, and (iii) the dominant positive Rac1(V12)
      mutant mimicked the effect of Nef. These results are to our knowledge the first
      analysis of the effect of Rac activation on the NADPH oxidase in intact
      phagocytes. Rac activation is not sufficient to stimulate the phagocyte NADPH
      oxidase; however, it markedly enhances the NADPH oxidase response to other
      stimuli.

PMID- 12207013
TI  - Phosphorylation of threonine 210 and the role of serine 137 in the regulation of
      mammalian polo-like kinase.
AB  - The mammalian polo-like kinase (Plk) plays a critical role in M-phase
      progression. Plk is phosphorylated and activated by an upstream kinase(s), which
      has not yet been identified in mammalian cells. Phosphopeptide mapping and
      phosphoamino acid analyses of Plk labeled in vivo and phosphorylated in vitro by
      Xenopus polo-like kinase kinase-1 (xPlkk1) or by lymphocyte-oriented kinase, its
      most closely related mammalian enzyme, indicate that Thr-210 is a major
      phosphorylation site in activated Plk from mitotic HeLa cells. Although the amino
      acid sequence surrounding Ser-137 is similar to that at Thr-210 and is conserved
      in Plk family members, Ser-137 is not detectably phosphorylated in mitotic
      mammalian cells or by xPlkk1 in vitro. Nevertheless, the substitution of either
      Thr-210 or Ser-137 with Asp (T210D or S137D) elevates the kinase activity of Plk.
      The kinase activity of the double mutant S137D/T210D is not significantly
      different from that of T210D or S137D, demonstrating that substitution of both
      residues does not have an additive effect on Plk activity. Expression of the
      S137D mutant construct arrested HeLa cells in early S-phase with slightly
      separated centrosomes, whereas cells expressing wild type and T210D were arrested
      or delayed in M-phase. These data indicate that the Ser-137 may have an
      unexpected and novel role in the function of Plk.

PMID- 12207014
TI  - The presence of chlorophyll b in Synechocystis sp. PCC 6803 disturbs tetrapyrrole
      biosynthesis and enhances chlorophyll degradation.
AB  - Both chlorophyll (Chl) a and b accumulate in the light in a Synechocystis sp. PCC
      6803 strain that expresses higher plant genes coding for a light-harvesting
      complex II protein and Chl a oxygenase. This cyanobacterial strain also lacks
      photosystem (PS) I and cannot synthesize Chl in darkness because of the lack of
      chlL. When this PS I-less/chlL(-)/lhcb(+)/cao(+) strain was grown in darkness,
      small amounts of two unusual tetrapyrroles, protochlorophyllide (PChlide) b and
      pheophorbide (pheide) b, were identified. Accumulation of PChlide b trailed that
      of PChlide a by several days, suggesting that PChlide a is an inefficient
      substrate of Chl a oxygenase. The presence of pheide b in this organism suggests
      a breakdown of Chl b via a pathway that does not involve conversion to a-type
      pigments. When the PS I-less/chlL(-) control strain was grown in darkness, Chl
      degradation was much slower than in the PS I-less/chlL(-)/lhcb(+)/cao(+) strain,
      suggesting that the presence of Chl b leads to more rapid turnover of Chl-binding
      proteins and/or a more active Chl degradation pathway. Levels and biosynthesis
      kinetics of Chl and of its biosynthetic intermediates are very different in the
      PS I-less/chlL(-)/lhcb(+)/cao(+) strain versus in the control. Moreover, when
      grown in darkness for 14 days, upon the addition of delta-aminolevulinic acid,
      the level of magnesium-protoporphyrin IX increased 60-fold in the PS I-less/chlL(
      )/lhcb(+)/cao(+) strain (only approximately 2-fold in the PS I-less/chlL(-)
      control strain), whereas the PChlide and protoheme levels remained fairly
      constant. We propose that a b-type PChlide, Chl, or pheide in the PS I-less/chlL(
      )/lhcb(+)/cao(+) strain may bind to tetrapyrrole biosynthesis regulatory
      protein(s) (for example, the small Cab-like proteins) and thus affect the
      regulation of this pathway.

PMID- 12207015
TI  - Cloning and characterization of mitochondrial 5-formyltetrahydrofolate
      cycloligase from higher plants.
AB  - 5-Formyltetrahydrofolate cycloligase (5-FCL) catalyzes the conversion of 5
      formyltetrahydrofolate (5-CHO-H(4)PteGlu(n)) to 5,10-methenyltetrahydrofolate and
      is considered to be the main means whereby 5-CHO-H(4)PteGlu(n) is metabolized in
      mammals, yeast, and bacteria. 5-CHO-H(4)PteGlu(n) is known to occur in plants and
      to be highly abundant in leaf mitochondria. Genomics-based approaches identified
      Arabidopsis and tomato cDNAs encoding proteins homologous to 5-FCLs of other
      organisms but containing N-terminal extensions with the features of mitochondrial
      targeting peptides. These homologs were shown to have 5-FCL activity by
      characterizing recombinant enzymes produced in Escherichia coli and by functional
      complementation of a yeast fau1 mutation with the Arabidopsis 5-FCL cDNA. The
      recombinant Arabidopsis enzyme is active as a monomer, prefers the penta- to the
      monoglutamyl form of 5-CHO-H(4)PteGlu(n), and has kinetic properties broadly
      similar to those of 5-FCLs from other organisms. Enzyme assays and immunoblot
      analyses indicated that 5-FCL is located predominantly if not exclusively in
      plant mitochondria and that the mature, active enzyme lacks the putative
      targeting sequence. Serine hydroxymethyltransferase (SHMT) from plant
      mitochondria was shown to be inhibited by 5-CHO-H(4)PteGlu(n) as are SHMTs from
      other organisms. Since mitochondrial SHMT is crucial to photorespiration, 5-FCL
      may help prevent 5-CHO-H(4)PteGlu(n) from reaching levels that would inhibit this
      process. Consistent with this possibility, 5-FCL activity was far higher in leaf
      mitochondria than root mitochondria.

PMID- 12207018
TI  - Electron transfer from the Rieske iron-sulfur protein (ISP) to cytochrome f in
      vitro. Is a guided trajectory of the ISP necessary for competent docking?
AB  - The time course of electron transfer in vitro between soluble domains of the
      Rieske iron-sulfur protein (ISP) and cytochrome f subunits of the cytochrome
      b(6)f complex of oxygenic photosynthesis was measured by stopped-flow mixing. The
      domains were derived from Chlamydomonas reinhardtii and expressed in Escherichia
      coli. The expressed 142-residue soluble ISP apoprotein was reconstituted with the
      [2Fe-2S] cluster. The second-order rate constant, k(2)((ISP-f)) = 1.5 x 10(6) m(
      1) s(-1), for ISP to cytochrome f electron transfer was <10(-2) of the rate
      constant at low ionic strength, k(2)((f-PC))(> 200 x 10(6) m(-1) s(-1)), for the
      reduction of plastocyanin by cytochrome f, and approximately 1/30 of k(2)((f-PC))
      at the ionic strength estimated for the thylakoid interior. In contrast to
      k(2)((f-PC)), k(2)((ISP-f)) was independent of pH and ionic strength, implying no
      significant role of electrostatic interactions. Effective pK values of 6.2 and
      8.3, respectively, of oxidized and reduced ISP were derived from the pH
      dependence of the amplitude of cytochrome f reduction. The first-order rate
      constant, k(1)((ISP-f)), predicted from k(2)((ISP-f)) is approximately 10 and
      approximately 150 times smaller than the millisecond and microsecond phases of
      cytochrome f reduction observed in vivo. It is proposed that in the absence of
      electrostatic guidance, a productive docking geometry for fast electron transfer
      is imposed by the guided trajectory of the ISP extrinsic domain. The requirement
      of a specific electrically neutral docking configuration for ISP electron
      transfer is consistent with structure data for the related cytochrome bc(1)
      complex.

PMID- 12207016
TI  - Specific characterization of substrate and inhibitor binding sites of a glycosyl
      hydrolase family 11 xylanase from Aspergillus niger.
AB  - The importance of aromatic and charged residues at the surface of the active site
      of a family 11 xylanase from Aspergillus niger was evaluated using site-directed
      mutagenesis. Ten mutant proteins were heterologously produced in Pichia pastoris,
      and their biochemical properties and kinetic parameters were determined. The
      specific activity of the Y6A, Y10A, Y89A, Y164A, and W172A mutant enzymes was
      drastically reduced. The low specific activities of Y6A and Y89A were entirely
      accounted for by a change in k(cat) and K(m), respectively, whereas the lower
      values of Y10A, Y164A, and W172A were due to a combination of increased K(m) and
      decreased k(cat). Tyr(6), Tyr(10), Tyr(89), Tyr(164), and Trp(172) are proposed
      as substrate-binding residues, a finding consistent with structural sequence
      alignments of family 11 xylanases and with the three-dimensional structure of the
      A. niger xylanase in complex with the modeled xylobiose. All other variants,
      D113A, D113N, N117A, E118A, and E118Q, retained full wild-type activity. Only
      N117A lost its sensitivity to xylanase inhibitor protein I (XIP-I), a protein
      inhibitor isolated from wheat, and this mutation did not affect the fold of the
      xylanase as revealed by circular dichroism. The N117A variant showed kinetics, pH
      stability, hydrolysis products pattern, substrate specificity, and structural
      properties identical to that of the wild-type xylanase. The loss of inhibition,
      as measured in activity assays, was due to abolition of the interaction between
      XIP-I and the mutant enzyme, as demonstrated by surface plasmon resonance and
      electrophoretic titration. A close inspection of the three-dimensional structure
      of A. niger xylanase suggests that the binding site of XIP-I is located at the
      conserved "thumb" hairpin loop of family 11 xylanases.

PMID- 12207017
TI  - Roles of Mcm7 and Mcm4 subunits in the DNA helicase activity of the mouse
      Mcm4/6/7 complex.
AB  - Mcm, which is composed of six structurally related subunits (Mcm2-7), is
      essential for eukaryotic DNA replication. A subassembly of Mcm, the Mcm4/6/7
      double-trimeric complex, possesses DNA helicase activity, and it has been
      proposed that Mcm may function as a replicative helicase at replication forks. We
      show here that conserved ATPase motifs of Mcm7 are essential for ATPase and DNA
      helicase activities of the Mcm4/6/7 complex. Because uncomplexed Mcm7 displayed
      neither ATPase nor DNA helicase activity, Mcm7 contributes to the DNA helicase
      activity of the Mcm complex through interaction with other subunits. In contrast,
      the Mcm4/6/7 complex containing a zinc finger mutant of Mcm4 with partially
      impaired DNA binding activity exhibited elevated DNA helicase activity. The
      Mcm4/6/7 complex containing this Mcm4 mutant tended to dissociate into trimeric
      complexes, suggesting that the zinc finger of Mcm4 is involved in subunit
      interactions of trimers. The Mcm4 mutants lacking the N-terminal 35 or 112 amino
      acids could form hexameric Mcm4/6/7 complexes, but displayed very little DNA
      helicase activity. In conjunction with the previously reported essential role of
      Mcm6 in ATP binding (You, Z., Komamura, Y., and Ishimi, Y. (1999) Mol. Cell.
      Biol. 19, 8003-8015), our data indicate distinct roles of Mcm4, Mcm6, and Mcm7
      subunits in activation of the DNA helicase activity of the Mcm4/6/7 complex.

PMID- 12207019
TI  - Structure-function analysis of Escherichia coli DNA helicase I reveals non
      overlapping transesterase and helicase domains.
AB  - TraI (DNA helicase I) is an Escherichia coli F plasmid-encoded protein required
      for bacterial conjugative DNA transfer. The protein is a sequence-specific DNA
      transesterase that provides the site- and strand-specific nick required to
      initiate DNA strand transfer and a 5' to 3' DNA helicase that unwinds the F
      plasmid to provide the single-stranded DNA that is transferred from donor to
      recipient. Sequence comparisons with other transesterases and helicases suggest
      that these activities reside in the N- and C-terminal regions of TraI,
      respectively. Computer-assisted secondary structure probability analysis
      identified a potential interdomain region spanning residues 304-309. Proteins
      encoded by segments of traI, whose N or C terminus either flanked or coincided
      with this region, were purified and assessed for catalytic activity. Amino acids
      1-306 contain the transesterase activity, whereas amino acids 309-1504 contain
      the helicase activity. The C-terminal 252 amino acids of the 1756-amino acid TraI
      protein are not required for either helicase or transesterase activity. Protein
      and nucleic acid sequence similarity searches indicate that the occurrence of
      both transesterase- and helicase-associated motifs in a conjugative DNA transfer
      initiator protein is rare. Only two examples (other than R100 plasmid TraI) were
      found: R388 plasmid TrwC and R46 plasmid (pKM101) TraH, belonging to the IncW and
      IncN groups of broad host range conjugative plasmids, respectively. The most
      significant structural difference between these proteins and TraI is that TraI
      contains an additional region of approximately 650 residues between the
      transesterase domain and the helicase-associated motifs. This region is required
      for helicase activity.

PMID- 12207020
TI  - Crystal structure of OxyB, a cytochrome P450 implicated in an oxidative phenol
      coupling reaction during vancomycin biosynthesis.
AB  - Gene-inactivation studies point to the involvement of OxyB in catalyzing the
      first oxidative phenol coupling reaction during glycopeptide antibiotic
      biosynthesis. The oxyB gene has been cloned and sequenced from the vancomycin
      producer Amycolatopsis orientalis, and the hemoprotein has been produced in
      Escherichia coli, crystallized, and its structure determined to 1.7-A resolution.
      OxyB gave UV-visible spectra characteristic of a P450-like hemoprotein in the low
      spin ferric state. After reduction to the ferrous state by dithionite or by
      spinach ferredoxin and ferredoxin reductase, the CO-ligated form gave a 450-nm
      peak in a UV-difference spectrum. Addition of putative heptapeptide substrates to
      resting OxyB produced type I changes to the UV spectrum, but no turnover was
      observed in the presence of ferredoxin and ferredoxin reductase, showing that
      either the peptides or the reduction system, or both, are insufficient to support
      a full catalytic cycle. OxyB exhibits the typical P450-fold, with helix L
      containing the signature sequence FGHGXHXCLG and Cys(347) being the proximal
      axial thiolate ligand of the heme iron. The structural similarity of OxyB is
      highest to P450nor, P450terp, CYP119, and P450eryF. In OxyB, the F and G helices
      are rotated out of the active site compared with P450nor, resulting in a much
      more open active site, consistent with the larger size of the presumed
      heptapeptide substrate.

PMID- 12207021
TI  - The cystine knot promotes folding and not thermodynamic stability in vascular
      endothelial growth factor.
AB  - Cystine knots consist of three intertwined disulfide bridges and are considered
      major determinants of protein stability in proteins in which they occur. We
      questioned this function and observed that removal of individual disulfide
      bridges in human vascular endothelial growth factor (VEGF) does not reduce its
      thermodynamic stability but reduces its unexpected high thermal stability of 108
      degrees C by up to 40 degrees C. In wild-type VEGF (deltaG(u,25)(0) = 5.1
      kcal.mol(-1)), the knot is responsible for a large entropic stabilization of
      TdeltaS(u,25)(0) = -39.3 kcal mol(-1), which is compensated for by a
      deltaH(u,25)(0) of -34.2 kcal mol(-1). In the disulfide-deficient mutants, this
      entropic stabilization disappears, but instead of a decrease, we observe an
      increase in the thermodynamic stability by about 2 kcal.mol(-1). A detailed
      crystallographic analysis of the mutant structures suggests a role of the cystine
      knot motif in protein folding rather than in the stabilization of the folded
      state. When assuming that the sequential order of the disulfide bridge formation
      is conserved between VEGF and glycoprotein alpha-subunit, the crystal structure
      of the mutant C61A-C104A, which deviates by a root mean square deviation of more
      than 2.2 A from wild-type VEGF, identifies a true folding intermediate of VEGF.

PMID- 12207022
TI  - Structural consequences of cardiac troponin I phosphorylation.
AB  - beta-Adrenergic stimulation of the heart results in bisphosphorylation of the N
      terminal extension of cardiac troponin I (TnI). Bisphosphorylation of TnI reduces
      the affinity of the regulatory site on troponin C (TnC) for Ca(2+) by increasing
      the rate of Ca(2+) dissociation. What remains unclear is how the phosphorylation
      signal is transmitted from one subunit of troponin to another. We have produced a
      series of mutations in the N-terminal extension of TnI designed to further our
      understanding of the mechanisms involved. The ability of phosphorylation of the
      mutant TnIs to affect Ca(2+) sensitivity has been assessed. We find that the Pro
      residues found in a conserved (Xaa-Pro)(4) motif N-terminal to the
      phosphorylation sites are not required for the effect of the N-terminal extension
      on Ca(2+) binding in the presence or absence of phosphorylation. Our experiments
      also reveal that the full effects of phosphorylation are seen even when residues
      1-15 of TnI are deleted. If further residues are removed, not only does the
      effect of phosphorylation diminish but deletion of the N-terminal extension
      mimics phosphorylation. We propose that TnI residues 16-29 bind to TnC
      stabilizing the "open" Ca(2+)-bound state. Phosphorylation (or deletion) prevents
      this binding, accelerating Ca(2+) release.

PMID- 12207023
TI  - Intrinsically slow dynamic instability of HeLa cell microtubules in vitro.
AB  - The dynamic behavior of mammalian microtubules has been extensively studied, both
      in living cells and with microtubules assembled from purified brain tubulin. To
      understand the intrinsic dynamic behavior of mammalian nonneural microtubules, we
      purified tubulin from cultured HeLa cells. We find that HeLa cell microtubules
      exhibit remarkably slow dynamic instability, spending most of their time in an
      attenuated state. The tempered dynamics contrast sharply with the dynamics of
      microtubules prepared from purified bovine brain tubulin under similar
      conditions. In accord with their minimal dynamic instability, assembled HeLa cell
      microtubules displayed a slow treadmilling rate and a low guanosine-5'
      triphosphate hydrolysis rate at steady state. We find that unlike brain tubulin,
      which consists of a heterogeneous mixture of beta-tubulin isotypes (beta(II),
      beta(III), and beta(IV) and a low level of beta(I)), HeLa cell tubulin consists
      of beta(I) tubulin ( approximately 80%) and a minor amount of beta(IV) tubulin (
      approximately 20%). The slow dynamic behavior of HeLa cell microtubules in vitro
      differs strikingly from the dynamic behavior of microtubules in living cultured
      mammalian cells, supporting the idea that accessory factors create the robust
      dynamics that occur in cells.

PMID- 12207024
TI  - Identification of a novel maturation mechanism and restricted substrate
      specificity for the SspB cysteine protease of Staphylococcus aureus.
AB  - The SspB cysteine protease of Staphylococcus aureus is expressed in an operon,
      flanked by the sspA serine protease, and sspC, encoding a 12.9-kDa protein of
      unknown function. SspB was expressed as a 40-kDa prepropeptide pSspB, which did
      not undergo autocatalytic maturation. Activity of pSspB was reduced compared with
      22-kDa mature SspB, but it was equivalent to mature SspB after incubation with
      SspA, which specifically removed the pSspB N-terminal propeptide. SspC abrogated
      the activity of pSspB when incubated in a 1:1 complex but had no effect on SspA
      or papain. Activity of the pSspB.SspC complex was restored when incubated with
      SspA, and SspC was cleaved by SspA but not pSspB. Thus, SspC maintains pSspB as
      an inert zymogen, and SspA is required for removal of the propeptide and
      inactivation of SspC. Like the papain protease family, SspB cleaved substrates
      with a hydrophobic amino acid at P2 but had a strong preference for arginine at
      P1. It did not cleave casein, serum albumin, IgG, or IgA, but it promoted
      detachment of cultured keratinocytes and cleaved fibronectin and fibrinogen at
      sites recognized by urokinase plasminogen activator and plasmin, respectively. It
      also processed high molecular weight kininogen in a manner resembling plasma
      kallikrein. Thus, SspB exhibits a novel maturation mechanism and mimics the
      specificity of plasma serine proteases.

PMID- 12207025
TI  - Crystal structure of porcine mitochondrial NADP+-dependent isocitrate
      dehydrogenase complexed with Mn2+ and isocitrate. Insights into the enzyme
      mechanism.
AB  - The crystal structure of porcine heart mitochondrial NADP+-dependent isocitrate
      dehydrogenase (IDH) complexed with Mn2+ and isocitrate was solved to a resolution
      of 1.85 A. The enzyme was expressed in Escherichia coli, purified as a fusion
      protein with maltose binding protein, and cleaved with thrombin to yield
      homogeneous enzyme. The structure was determined by multiwavelength anomalous
      diffraction phasing using selenium substitution in the form of selenomethionine
      as the anomalous scatterer. The porcine NADP+-IDH enzyme is structurally compared
      with the previously solved structures of IDH from E. coli and Bacillus subtilis
      that share 16 and 17% identity, respectively, with the mammalian enzyme. The
      porcine enzyme has a protein fold similar to the bacterial IDH structures with
      each monomer folding into two domains. However, considerable differences exist
      between the bacterial and mammalian forms of IDH in regions connecting core
      secondary structure. Based on the alignment of sequence and structure among the
      porcine, E. coli, and B. subtilis IDH, a putative phosphorylation site has been
      identified for the mammalian enzyme. The active site, including the bound Mn2+
      isocitrate complex, is highly ordered and, therefore, mechanistically
      informative. The consensus IDH mechanism predicts that the Mn2+-bound hydroxyl of
      isocitrate is deprotonated prior to its NADP+-dependent oxidation. The present
      crystal structure has an active site water that is well positioned to accept the
      proton and ultimately transfer the proton to solvent through an additional bound
      water.

PMID- 12207026
TI  - Evidence for regulation of the tumor necrosis factor alpha-convertase (TACE) by
      protein-tyrosine phosphatase PTPH1.
AB  - Tumor necrosis factor alpha-convertase (TACE) is a metalloprotease-disintegrin
      involved in the ectodomain shedding of several proteins and is critical for
      proper murine development. TACE-mediated ectodomain shedding is regulated, and
      the cytoplasmic domain of TACE contains several potential signaling motifs,
      suggesting that this domain may play a role in regulating the metalloprotease
      activity. Here we report that the protein-tyrosine phosphatase PTPH1, which
      contains both a band 4.1 domain and a single PDZ domain, can interact with the
      cytoplasmic domain of TACE. The interaction was initially observed in a yeast two
      hybrid screen and was confirmed using an in vitro binding assay and co
      immunoprecipitations from eukaryotic cell extracts. The interaction is mediated
      via binding of the PDZ domain of PTPH1 to the COOH terminus of TACE. The latter
      represents a novel group I PDZ binding sequence characterized by a terminal
      cysteine residue. In co-expression experiments, significantly lower levels of
      TACE were observed in the presence of catalytically active forms of PTPH1
      compared with catalytically inactive forms of PTPH1. Furthermore, phorbol ester
      stimulated shedding of the TACE substrate tumor necrosis factor-alpha was
      decreased in cells expressing catalytically active PTPH1 compared with inactive
      PTPH1. Taken together, these results suggest that PTPH1 may be a negative
      regulator of TACE levels and function, and thus provide the first evidence for
      the regulation of TACE through a cytoplasmic protein.

PMID- 12207027
TI  - Autocatalytic processing of gamma-glutamyltranspeptidase.
AB  - gamma-Glutamyltranspeptidase is the key enzyme in glutathione metabolism, and we
      previously presented evidence suggesting that it belongs to the N-terminal
      nucleophile hydrolase superfamily. Enzymatically active gamma
      glutamyltranspeptidase, which consists of one large subunit and one small
      subunit, is generated from an inactive common precursor through post
      translational proteolytic processing. The processing mechanism for gamma
      glutamyltranspeptidase of Escherichia coli K-12 has been analyzed by means of in
      vitro studies using purified precursors. Here we show that the processing of a
      precursor of gamma-glutamyltranspeptidase is an intramolecular autocatalytic
      event and that the catalytic nucleophile for the processing reaction is the
      oxygen atom of the side chain of Thr-391 (N-terminal residue of the small (beta)
      subunit), which is also the nucleophile for the enzymatic reaction.

PMID- 12207028
TI  - Effect of Bcl-2 overexpression on mitochondrial structure and function.
AB  - Overexpression of the antiapoptotic Bcl-2 protein enhances the uptake of
      fluorimetric dyes sensitive to mitochondrial membrane potential, suggesting that
      Bcl-2 changes the mitochondrial proton gradient. In this study, we performed
      calibrated measurements of mitochondrial respiration, membrane potential,
      deltapH, and intramitochondrial [K+] in digitonin-permeabilized PC12 and GT1-7
      neural cells that either do not express human Bcl-2 (control transfectants) or
      that were transfected with and overexpressed the human bcl-2 gene to evaluate
      whether Bcl-2 alters mitochondrial inner membrane ion transport. We found that
      although Bcl-2-overexpressing cells exhibit higher fluorescence responses to
      membrane potential, pH, and K+-sensitive dyes, this increased response is due to
      an enhanced accumulation of these dyes and not an increased mitochondrial
      membrane potential, deltapH, or [K+]. This result is supported by the presence of
      equal respiratory rates in Bcl-2+ and Bcl-2- cells. Possible structural
      alterations in Bcl-2+ mitochondria that could account for increases in
      fluorescent dye uptake were evaluated using flow cytometry particle sizing and
      light scattering determinations. These experiments established that Bcl-2
      overexpressing mitochondria present both increased volume and structural
      complexity. We suggest that increased mitochondrial volume and structural
      complexity in Bcl-2+ cells may be related to many of the effects of this protein
      involved in the prevention of cell death.

PMID- 12207029
TI  - Dissection of the functional differences between sarco(endo)plasmic reticulum
      Ca2+-ATPase (SERCA) 1 and 3 isoforms by steady-state and transient kinetic
      analyses.
AB  - Steady-state and transient-kinetic studies were conducted to characterize the
      overall and partial reactions of the Ca(2+)-transport cycle mediated by the human
      sarco(endo)plasmic reticulum Ca(2+)-ATPase 3 (SERCA3) isoforms: SERCA3a, SERCA3b,
      and SERCA3c. Relative to SERCA1a, all three human SERCA3 enzymes displayed a
      reduced apparent affinity for cytosolic Ca(2+) in activation of the overall
      reaction due to a decreased E(2) to E(1)Ca(2) transition rate and an increased
      rate of Ca(2+) dissociation from E(1)Ca(2). At neutral pH, the ATPase activity of
      the SERCA3 enzymes was not significantly enhanced upon permeabilization of the
      microsomal vesicles with calcium ionophore, indicating a difference from SERCA1a
      with respect to regulation of the lumenal Ca(2+) level (either an enhanced efflux
      of lumenal Ca(2+) through the pump in E(2) form or insensitivity to inhibition by
      lumenal Ca(2+)). Other differences from SERCA1a with respect to the overall
      ATPase reaction were an alkaline shift of the pH optimum, increased catalytic
      turnover rate at pH optimum (highest for SERCA3b, the isoform with the longest C
      terminus), and an increased sensitivity to inhibition by vanadate that
      disappeared under equilibrium conditions in the absence of Ca(2+) and ATP. The
      transient-kinetic analysis traced several of the differences from SERCA1a to an
      enhancement of the rate of dephosphorylation of the E(2)P phosphoenzyme
      intermediate, which was most pronounced at alkaline pH and increased with the
      length of the alternatively spliced C terminus.

PMID- 12207030
TI  - Molecular configuration of xanthophyll cycle carotenoids in photosystem II
      antenna complexes.
AB  - The molecular configuration of the xanthophyll cycle carotenoids, violaxanthin
      and zeaxanthin, was studied in various isolated photosystem II antenna components
      in comparison to intact photosystem II membranes using resonance Raman combined
      with low-temperature absorption spectroscopy. The molecular configurations of
      zeaxanthin and violaxanthin in thylakoids and isolated photosystem II membranes
      were found to be the same within an isolated oligomeric LHCII antenna, confirming
      our recent conclusion that these molecules are not freely located in
      photosynthetic membranes (Ruban, A. V., Pascal, A. A., Robert, B., and Horton, P.
      (2001) J. Biol. Chem. 276, 24862-24870). In contrast, xanthophyll cycle
      carotenoids bound to LHCII trimers had largely lost their in vivo configuration,
      suggesting their partial dissociation from the binding locus. Violaxanthin and
      zeaxanthin associated with the minor antenna complexes, CP26 and CP29, were also
      found to be in a relaxed configuration, similar to that of free pigment. The
      origin of the characteristic C-H vibrational bands of violaxanthin and zeaxanthin
      in vivo is discussed by comparison with those of neoxanthin and lutein in
      oligomeric and trimeric LHCII respectively.

PMID- 12207031
TI  - Volume exclusion effect as a driving force for reverse proteolysis. Implications
      for polypeptide assemblage in a macromolecular crowded milieu.
AB  - Macromolecular crowding, in principle, should affect any reaction that is
      accompanied by significant reduction in excluded volume. Here we have examined
      the influence of crowding on reverse proteolysis. We show that proteosynthesis of
      a polypeptide product with an interacting folding motif such as coiled coil is
      facilitated in crowded media as a consequence of the volume exclusion effect.
      Further, we demonstrate that crowding could also effect the conversion of a
      noncovalent protein complex (fragment complementing protein) obtained by limited
      proteolysis to the native covalent form, but only if the formation of the native
      protein results in large compaction leading to a substantial volume exclusion
      effect. Subtilisin-catalyzed reformation of native triosephosphate isomerase
      (TIM) from multiple fragments is facilitated by crowding. However, a single nick
      in ribonuclease S (RNase S) could not be ligated under similar conditions. The
      failure of generation of RNase A from RNase S is consistent with the fact that
      the crystal structure of the two forms are almost superimposable, and hence no
      significant difference of volume exclusion exists between reactant (RNase S) and
      product (RNase A). In contrast, considerable compaction, and consequently large
      reduction in excluded volume, is attained through the assembly of a TIM barrel
      structure. Taken together, these results have implications for both in vitro as
      well as in vivo polypeptide assemblage by reverse proteolysis.

PMID- 12207032
TI  - Structural conservation between the actin monomer-binding sites of twinfilin and
      actin-depolymerizing factor (ADF)/cofilin.
AB  - Twinfilin is an evolutionarily conserved actin monomer-binding protein that
      regulates cytoskeletal dynamics in organisms from yeast to mammals. It is
      composed of two actin-depolymerization factor homology (ADF-H) domains that show
      approximately 20% sequence identity to ADF/cofilin proteins. In contrast to
      ADF/cofilins, which bind both G-actin and F-actin and promote filament
      depolymerization, twinfilin interacts only with G-actin. To elucidate the
      molecular mechanisms of twinfilin-actin monomer interaction, we determined the
      crystal structure of the N-terminal ADF-H domain of twinfilin and mapped its
      actin-binding site by site-directed mutagenesis. This domain has similar overall
      structure to ADF/cofilins, and the regions important for actin monomer binding in
      ADF/cofilins are especially well conserved in twinfilin. Mutagenesis studies show
      that the N-terminal ADF-H domain of twinfilin and ADF/cofilins also interact with
      actin monomers through similar interfaces, although the binding surface is
      slightly extended in twinfilin. In contrast, the regions important for actin
      filament interactions in ADF/cofilins are structurally different in twinfilin.
      This explains the differences in actin-interactions (monomer versus filament
      binding) between twinfilin and ADF/cofilins. Taken together, our data show that
      the ADF-H domain is a structurally conserved actin-binding motif and that
      relatively small structural differences at the actin interfaces of this domain
      are responsible for the functional variation between the different classes of ADF
      H domain proteins.

PMID- 12207034
TI  - Core protein dependence of epimerization of glucuronosyl residues in
      galactosaminoglycans.
AB  - Chondroitin sulfate and dermatan sulfate proteoglycans are distinguished by
      differences in their proportion of d-glucuronosyl and l-iduronosyl residues, the
      latter being formed by chondroitin-glucuronate 5-epimerase during or after
      glycosaminoglycan chain polymerization. To investigate the influence of the core
      protein on the extent of epimerization, we expressed chimeric proteins in 293 HEK
      cells constructed from intact or modified Met(1)-Gln(153) of decorin (DCN), which
      normally has a single dermatan sulfate chain at Ser(34), in combination with
      intact or modified Leu(241)-Ser(353) of CSF-1, which has a chondroitin sulfate
      attachment site at Ser(309). Transfected DCN(M1-Q153), like full-length DCN,
      contained approximately 20% l-iduronate. Conversely, transfected CSF-1(L241
      S353), attached C-terminally on the DCN prepropeptide, contained almost
      exclusively d-glucuronate. Transfected intact chimeric DCN(M1-Q153)-CSF-1(L241
      S353), with two glycosaminoglycan chains, also contained almost exclusively d
      glucuronate in chains at both sites, as did chimeras in which alanine was
      substituted for serine at either of the glycosaminoglycan attachment sites.
      Nevertheless, undersulfated intact chimeric proteoglycan was an effective
      substrate for epimerization of glucuronate to iduronate residues when incubated
      with microsomal proteins and 3'-phosphoadenylylphosphosulfate. C-terminal
      truncation constructs were prepared from the full-length chimera with an alanine
      substitution at the CSF-1 glycosaminoglycan attachment site. Transfected
      truncations retaining the alanine-blocked site contained chains with essentially
      only glucuronate, whereas those further truncated by 49 or more amino acids and
      missing the modified attachment site contained chains with approximately 15%
      iduronate. This 49-amino acid region contains a 7-amino acid motif that appears
      to be conserved in several chondroitin sulfate proteoglycans. The results are
      consistent with a model in which the core protein, possibly via this motif, is
      responsible for routing to subcellular compartments with or without sufficient
      access to chondroitin-glucuronate 5-epimerase for the addition of chains with or
      without iduronate residues, respectively.

PMID- 12207033
TI  - Double-stranded RNA-dependent protein kinase (pkr) is essential for
      thermotolerance, accumulation of HSP70, and stabilization of ARE-containing HSP70
      mRNA during stress.
AB  - We have investigated the role of the double-stranded RNA-dependent protein kinase
      gene (pkr) in the regulation of the heat shock response. We show that the pkr
      gene is essential for efficient activation of the heat shock response and that
      pkr disruption profoundly inhibits heat shock protein 70 (HSP70) synthesis and
      blocks the development of thermotolerance. Despite these profound effects, pkr
      disruption did not markedly affect the activation of heat shock factor 1 by heat
      and did not reduce the rate of transcription of the HSP70 gene after heat shock.
      However, despite the lack of effect of pkr disruption on HSP70 gene
      transcription, we found a significant decrease in the expression of HSP70 mRNA in
      pkr-/- cells after heat shock. Kinetic studies of mRNA turnover suggested a block
      in the thermal stabilization of HSP70 mRNA in pkr-/- cells. As the thermal
      stabilization of HSP70 mRNA is thought to involve cis-acting A+U rich (ARE)
      elements in the 3'-untranslated region (UTR), we examined a potential role for
      pkr in this process. We found that a reporter beta-galactosidase mRNA
      destabilized by introduction of a functional ARE into the 3'-UTR became
      stabilized by heat but only in cells containing an intact pkr gene. Our studies
      suggest therefore that pkr plays a significant role in the stabilization of mRNA
      species containing ARE destruction sequences in the 3'-UTR and through this
      mechanism, contributes to the regulation of the heat shock response and other
      processes.

PMID- 12207035
TI  - Gene cluster for ferric iron uptake in Agrobacterium tumefaciens MAFF301001.
AB  - Agrobacterium tumefaciens harboring a Ti plasmid causes crown gall disease in
      dicot plants by transferring its T-DNA into plant chromosomes. Iron acquisition
      plays an important role for pathogenicity in animal pathogens and several
      phytopathogens and for growth in the rhizosphere and on plant surfaces. Under
      iron-limiting condition, bacteria produce various iron-chelating agents called
      siderophores. Agrobacterium strains have the diversity in producing siderophores
      and a certain strain produces a typical catechol-type siderophore, called
      agrobactin, although its biosynthesis genes have not been analyzed yet. Here we
      describe the cloning and characterization of a functional gene cluster involved
      in ferric iron uptake in A. tumefaciens strain MAFF301001. Four complete open
      reading frames (ORFs) were found in 5-kb region of a genomic library clone 1A3.
      We named these genes agb, after agrobactin. agbC, agbE, agbB and agbA genes were
      identified in this order, and narrow intergenic spaces suggested that these genes
      constitute an operon. Predicted agb gene products and their phylogenetic analysis
      showed sequence similarity with enzymes which are involved in ferric iron uptake
      in other bacteria. Southern hybridization analysis clearly indicated the location
      of agb genes on the linear chromosome in strain MAFF301001 but the complete lack
      in another A. tumefaciens strain C58. Mutation analysis of agbB revealed that it
      is essential for growth and production of catechol compounds in iron-limiting
      medium.

PMID- 12207036
TI  - The fission yeast RPA21 subunit of RNA polymerase I: an evolutionarily conserved
      subunit interacting with ribosomal DNA (rDNA) transcription factor Rrn3p for
      recruitment to rDNA promoter.
AB  - Recruitment of RNA polymerases to the cognate promoter is a key step for the
      transcription initiation of specific genes in eukaryotes. Recently, RNA
      polymerase I (pol I) of Saccharomyces cerevisiae was shown to be recruited to the
      rDNA promoter via interaction between Rrn3p, a conserved transcription factor for
      rDNA, and A43, a subunit specific to pol I. The question of whether a similar
      interaction for pol I recruitment is conserved in other eukaryotes remains to be
      answered. We show here that Schizosaccharomyces pombe rpa21(+) encodes a protein
      of apparent molecular mass 21 kD which shows 36% identity to the A43 subunit of
      pol I in S. cerevisiae, and that rpa21(+) is essential for cell growth. To gain
      further insight into the functions of RPA21, we isolated a total of 22
      temperature-sensitive (ts) mutants of rpa21(+) and found that most of the
      substitutions causing the ts phenotype are clustered in the N-terminal half of
      RPA21. The ts mutants showed a markedly reduced amount of primary transcripts of
      rDNA immediately after temperature shift-up. Over-expression of S. pombe rrn3(+)
      in the ts mutants suppressed the growth defect in an allele-specific manner.
      Therefore, we conclude that S. pombe RPA21 plays a functional role similar to
      that of A43 in S. cerevisiae and that the mechanism of recruitment of pol I to
      the rDNA promoter by the interaction of a specific pol I subunit with Rrn3p is
      evolutionarily conserved.

PMID- 12207037
TI  - Characterization of duplicated two cytosolic phosphoglucose isomerase (PgiC) loci
      in Arabidopsis halleri ssp. gemmifera.
AB  - Arabidopsis halleri ssp. gemmifera has two cytosolic phosphoglucose isomerase
      (PgiC) loci. A 48-bp deletion was observed in the junction of exon 17 and intron
      17 for a locus (PgiC2). PCR-RFLP analysis using cDNA template did not detect the
      PgiC2 locus. Another locus (PgiC1) has common structure with A. thaliana and
      expressed normally. A phylogenetic tree of PgiC sequences revealed that
      duplication of the two loci in A. gemmifera occurred after species splitting of
      A. thaliana and A. gemmifera. More than 12 kb region encompassing PgiC was
      sequenced for both loci. In both PgiC1 and PgiC2, sequence homologous to A.
      thaliana PgiC 5' upstream region was not detected. A gene located on chromosome 4
      of A. thaliana was detected in the 5' upstream of PgiC2. This result suggested
      that the microsyntheny around the PgiC region between A. thaliana and A.
      gemmifera is not established.

PMID- 12207038
TI  - DNA variation in the acidic chitinase locus (ChiA) region in Arabis gemmifera and
      its related species.
AB  - We analyzed DNA variation at the acidic chitinase (ChiA) locus of Arabis
      gemmifera and among its eight related species. Nucleotide diversity (pi) of the
      entire locus in A. gemmifera was 0.0032, which was one third that of A. thaliana.
      In A. gemmifera, an excess of unique polymorphisms yielded significantly negative
      results with the tests of Tajima and Fu and Li. The McDonald and Kreitman test
      revealed that the ratio of nucleotide replacement to synonymous changes in A.
      gemmifera was significantly greater than those between A. gemmifera and A.
      glabra, A. gemmifera and A. griffithiana, A. gemmifera and A. korshinskyi, A.
      gemmifera and A. wallichii, and A. gemmifera and A. himalaica. These results
      indicated that the neutrality assumption, the equilibrium population assumption,
      or both, could not be applied to the ChiA locus of A. gemmifera. The small size
      and relative isolation of local subpopulations of A. gemmifera could explain the
      excess of unique polymorphisms and the high proportion of replacement changes.
      The specific sampling scheme of this study, where one strain each was sampled
      from each local subpopulation might also have led to an excess of singletons.
      Interspecific comparison among Arabidopsis, Arabis and Cardaminopsis species
      showed that Ka was always lower than Ks, providing evidence against the adaptive
      evolution of ChiA. However, Ka/Ks was greater between closely related species
      than between more distant related species. ChiA had a higher level of replacement
      divergence and a lower level of synonymous divergence compared than did Adh. We
      suggest that both the mutation rate at the nucleotide level and the selective
      constraints at the protein level are lower in ChiA than in Adh.

PMID- 12207039
TI  - Genetic variation of Trigonobalanus verticillata, a primitive species of
      Fagaceae, in Malaysia revealed by chloroplast sequences and AFLP markers.
AB  - The genetic variation of Trigonobalanus verticillata, the most recently described
      genus of Fagaceae, was studied using chloroplast DNA sequences and AFLP
      fingerprinting. This species has a restricted distribution that is known to
      include seven localities in tropical lower montane forests in Malaysia and
      Indonesia. A total of 75 individuals were collected from Bario, Kinabalu, and
      Fraser's Hill in Malaysia. The sequences of rbcL, matK, and three non-coding
      regions (atpB-rbcL spacer, trnL intron, and trnL-trnF spacer) were determined for
      19 individuals from these populations. We found a total of 30 nucleotide
      substitutions and four length variations, which allowed identification of three
      haplotypes characterizing each population. No substitutions were detected within
      populations, while the tandem repeats in the trnL -trnF spacer had a variable
      repeat number of a 20-bp motif only in Kinabalu. The differentiation of the
      populations inferred from the cpDNA molecular clock calibrated with
      paleontological data was estimated to be 8.3 MYA between Bario and Kinabalu, and
      16.7 MYA between Fraser's Hill and the other populations. In AFLP analysis, four
      selective primer pairs yielded a total of 431 loci, of which 340 (78.9%) were
      polymorphic. The results showed relatively high gene diversity (H(S) = 0.153 and
      H(T) = 0.198) and nucleotide diversity (pi(S) = 0.0132 and pi(T) = 0.0168) both
      within and among the populations. Although the cpDNA data suggest that little or
      no gene flow occurred between the populations via seeds, the fixation index
      estimated from AFLP data (F(ST) = 0.153 and N(ST) = 0.214) implies that some gene
      flow occurs between populations, possibly through pollen transfer.

PMID- 12207040
TI  - Light wavelength dependency of mating activity in the Drosophila melanogaster
      species subgroup.
AB  - The action spectra of mating activity among the six species of the Drosophila
      melanogaster species subgroup were compared to understand how light wavelength
      affects mating activity. The species fell into three groups with respect to the
      action spectrum of mating activity. We chose one representative species from each
      of the three types for detailed study: D. melanogaster, D. sechellia and D.
      yakuba. The mating activities were investigated under three different light
      intensities of three monochromatic lights stimulus. Each species showed a unique
      spectral and intensity response. To know the evolutionary meaning of the light
      wavelength dependency of mating activity, we superimposed the type of action
      spectrum of mating activity in these six species on a cladogram. Mating
      inhibition under UV was conserved in evolution among these species. Furthermore
      we clarified that D. melanogaster showed low mating activity under UV because
      males courted less under UV.

PMID- 12207041
TI  - Changes in body temperature pattern in vertebrates do not influence the codon
      usages of alpha-globin genes.
AB  - Codon usages are known to vary among vertebrates chiefly due to variations in
      isochore structure. Under the assumption that marked differences exist in
      isochore structure between warm-blooded and cold-blooded animals, the variations
      among vertebrates were previously attributed to an adaptation to homeothermy.
      However, based on data from a turtle species and a crocodile (Archosauromorpha),
      it was recently proposed that the common ancestors of mammals, birds and extent
      reptiles already had the "warm-blooded" isochore structure. We determined the
      nucleotide sequences of alpha-globin genes from two species of heterotherms,
      cuckoo (Cuculus canorus) and bat (Pipistrellus abramus), and three species of
      snakes (Lepidosauromorpha), Naja kaouthia from a tropical terrestrial habitat,
      Elaphe climacophora from a temperate terrestrial habitat, and Hydrophis
      melanocephalus from a tropical marine habitat. Our purposes were to assess the
      influence of differential body temperature patterns on codon usage and GC content
      at the third position of a codon (GC3), and to test the hypothesis concerning the
      phylogenetic position at which GC contents had increased in vertebrates. The
      results of principal component analysis (PCA) using the present data and data for
      other taxa from GenBank indicate that the primary difference in codon usage in
      globin genes among amniotes and other vertebrates lies in GC3. The codon usages
      (and GC3) in alpha-globin genes from two heterotherms and three snakes are
      similar to those in alpha-globin genes from warm-blooded vertebrates. These
      results refute the influence of body temperature pattern upon codon usages (and
      GC3) in alpha-globin genes, and support the hypothesis that the increase in GC
      content in the genome occurred in the common ancestor of amniotes.

PMID- 12207042
TI  - On the efficiency of composite interval mapping in an outbred population.
AB  - Composite interval mapping (CIM) has been successfully applied to the detection
      of QTL in experimental animals and plants. However, practical analyses based on
      CIM have been reported mainly for populations derived from cross between inbred
      lines. There are few studies on QTL analyses with CIM in outbred populations. To
      evaluate the applicability of CIM to outbred populations is prerequisite for the
      fine mapping of QTL in industrial animals such as pig and chicken. Some markers
      are usually not fully informative in outbred populations. In application of CIM
      to outbred populations, the influence of inclusion of such uninformative markers
      used as covariates on the efficiency of CIM should be investigated. In this paper
      a least-squares method for CIM was formalized in an F(2) population derived by
      crossing two outbred lines. The efficiencies of CIM were evaluated for outbred
      populations in comparison with simple interval mapping (SIM) for several cases of
      marker informativeness using simulations. By incorporating markers linked to a
      tested position as well as those unlinked, CIM showed a higher efficiency to
      separate two linked QTL over SIM. The efficiency of dissection was enhanced as
      the marker informativeness was increased. The power of CIM to detect an isolated
      QTL was improved by excluding markers linked to a tested position from covariates
      and higher than SIM regardless of marker informativeness. In conclusion, CIM is a
      useful procedure for the analysis of QTL in outbred populations even under low
      marker informativeness.

PMID- 12207043
TI  - Effects of the phosphatase inhibitors, okadaic acid, ATPgammaS, and calyculin A
      on the dividing sand dollar egg.
AB  - The effects of the phosphatase inhibitors, okadaic acid (OA), adenosine 5'-O-(3
      thiotriphosphate) (ATPgammaS), and calyculin A (CL-A) on anaphase chromosome
      movement, cytokinesis, and cytoskeletal structures at cell division were examined
      by being microinjected into mitotic sand dollar eggs. When OA was injected,
      chromosome movement was inhibited and, moreover, chromosomes were ejected from
      the polar regions of the mitotic apparatus. By immunofluorescence, microtubules
      were observed to be severed in the OA-injected eggs, causing the smooth cell
      surface to be changed to an irregular surface. When ATPgammaS and CL-A were
      injected, the effect on cell shape was remarkable: In dividing eggs, furrowing
      stopped within several seconds after injection, small blebs appeared on the cell
      surface and became large, spherical or dumbbell cell shapes then changed to
      irregular forms, and subsequently cytoplasmic flow occurred. Microfilament
      detection revealed that actin accumulation in the cortex, which was not limited
      to the furrow cortex, occurred shortly after injection. Cortical accumulation of
      actin is thought to induce force generation and random cortical contraction, and
      accordingly to result in bleb extrusion from the cortex. Consequently, the
      phosphatase inhibitors inhibited the transition from mitosis to interphase by
      mediating cortical accumulation of actin filaments and/or fragmentation of
      microtubules.

PMID- 12207044
TI  - Gene expression of type I and type III collagen by mechanical stretch in anterior
      cruciate ligament cells.
AB  - Mechanical stretch affects the healing and remodeling process of the anterior
      cruciate ligament (ACL) after surgery in important ways. In this study, the
      effects of mechanical stress on gene expression of type I and III collagen by
      cultured human ACL cells and roles of transforming growth factor (TGF)-beta1 in
      the regulation of mechanical strain-induced gene expression were investigated.
      Uniaxial cyclic stretch was applied on ACL cells at 10 cycles/min with 10% length
      stretch for 24 h. mRNA expression of the type I and type III collagen was
      increased by the cyclic stretch. TGF-beta1 protein in the cell culture
      supernatant was also increased by the stretch. In the presence of anti-TGF-beta1
      antibody, stretch-induced increase in type I and type III mRNA expression was
      markedly ablated. The results suggest that the stretch-induced mRNA expression of
      the type I and type III collagen is mediated via an autocrine mechanism of TGF
      beta1 released from ligament cells.

PMID- 12207045
TI  - Evidence of a novel dipeptidyl aminopeptidase in mammalian GH(3) cells: new
      insights into the processing of peptide hormone precursors.
AB  - We investigated whether yeast signals could regulate hormone processing in
      mammalian cells. Chmeric genes coding for the prepro region of yeast alpha-factor
      and the functional hormone region of anglerfish somatostatin was expressed in rat
      pituitary GH(3) cells. The nascent prepro-alpha-factor-somatostatin peptides
      disappeared from cells with a half-life of 30 min, and about 20% of unprocessed
      precursors remained intracellular after a 2 h chase period. Disappearance of
      propeptide was insensitive to lysosomotropic agents, but was inhibited at 15
      degrees C or 20 degrees C, suggesting that the hybrid propeptides were not
      degraded in the secretory pathway to the trans Golgi network or in lysosomes. It
      appeared that while most unprocessed precursors were constitutively secreted into
      the medium, a small portion were processed at their paired dibasic sites by
      prohormone-processing enzymes located in trans Golgi network/secretory vesicles,
      resulting in the production of mature somatostatin peptides. To test this
      hypothesis, we investigated the processing pattern of two different hybrid
      precursors: the 52-1 hybrid precursor, which has a Glu-Ala spacer between the
      prepro region of alpha-factor and somatostatin, and the 58-1 hybrid precursor,
      which lacks the Glu-Ala spacer. Processing of metabolically labeled hybrid
      propeptides to smaller somatostatin peptides was assessed by HPLC. When pulse
      labeled cells were chased for up to 2 h, 68% of the initially synthesized
      propeptides were secreted constitutively. About 22% of somatostatin-related
      products were proteolytically processed to mature somatostatin, of which 38.7%
      were detected intracellularly after 2 h. From N-terminal peptide sequence
      determination of somatostatin-related products in GH(3)-52 and GH(3)-58 cells, we
      found that both hybrid precursors were accurately cleaved at their dibasic amino
      acid sites. Notably, we also observed that the Glu-Ala spacer sequence was
      removed from 52-1 hybrid precursors. The latter result strongly suggests that a
      novel dipeptidyl aminopeptidase activity - a yeast STE13-like enzyme - is present
      in the post-trans Golgi network compartment of GH(3) cells. The data from these
      studies indicate that mechanisms which control protein secretion are conserved
      between yeast and mammalian cells.

PMID- 12207046
TI  - Steryl glucoside is a lipid mediator in stress-responsive signal transduction.
AB  - We previously reported that steryl glucoside (SG) is rapidly induced in cells
      from molds to humans by exposure to environmental stress (Murakami-Murofushi et
      al. (1997) J. Biol. Chem., 272, 486-489, Kunimoto et al. (2000) Cell Stress &
      Chaperones, 5, 3-7), and in mold cells SG production is followed by activation of
      a certain protein kinase and induction of heat shock proteins (HSP) (Maruya et
      al. (1997) Cell Struct. Funct., 21, 533-538). To determine the biological
      significance of SG in stress responsive signal transduction, we added SG to the
      culture of human fibroblasts and examined its effect on HSP induction. We
      demonstrated a rapid activation of heat shock transcription factor 1 (HSF1) to
      bind to heat shock element (HSE) and induction of heat shock protein 70 (HSP70)
      in fibroblast cells by exposure to exogenously added human major SG, cholesteryl
      glucoside (CG). In addition, enzyme activity to form CG from cholesterol and UDP
      glucose was detected in the homogenate of fibroblast cells. These results
      strongly suggest that CG acts as a mediator in the early stage of stress
      responsive signal transduction.

PMID- 12207047
TI  - Utilization of liposomes in vesicular transport studies.
AB  - Various coated vesicles are implicated in the intracellular transport between
      different compartments. In vitro reconstitution is a powerful experimental system
      to study molecular mechanisms involved in assembly of coat proteins from cytosol
      onto membranes as well as formation of coated vesicles. Liposomes have been
      recently utilized in the cell-free systems. In this review, we summarize studies
      on reconstitutions of coated vesicles or coated structures on liposomes. A novel
      method using dynamic light scattering (DLS) to quantify vesicle formation from
      liposomes also is described. Our recent study on the role of phospholipids in
      vesicle formation, where the DSL assay is used in combination with lipid
      analysis, also is introduced.

PMID- 12207048
TI  - Development and characterization of conditionally immortalized gastric epithelial
      cell lines from transgenic rats harboring temperature-sensitive simian virus 40
      large T-antigen gene.
AB  - Conditionally immortalized gastric epithelial cell lines were established from
      transgenic rats harboring temperature-sensitive simian virus 40 (tsSV40) large T
      antigen gene. Gastric mucosal cells and epithelial tissues isolated from the
      stomach of the transgenic rats were cultured at permissive temperature (33
      degrees C), and proliferative cells were cloned by colony formation. Six cell
      lines (designated as RGE1-01, RGE1-02, RGE1-03, RGE1-21, RGE1-22 and RGE2-01)
      showing epithelial-like morphology have been established. All cells grew at 33
      degrees C, but did not at nonpermissive temperature (39 degrees C). High
      expression level of large T-antigen in the nuclei was observed at 33 degrees C,
      whereas the expression level was gradually decreased in a time-dependent manner
      at 39 degrees C. These results suggest that the temperature-sensitive growth
      characteristics arise as a result of a function of the tsSV40 large T-antigen.
      None of the cell lines were transformed as judged by anchorage-independent growth
      assay. Immunocytochemical findings indicated that all cells expressed epithelial
      cell markers including cytoskeletal (cytokeratin and actin), basement membrane
      (laminin and collagen type IV) and junctional complex (ZO-1 and desmoplakin I+II)
      proteins at 33 degrees C. All cells expressed mRNA of cathepsin E, a pit cell
      marker. Moreover, transepithelial resistance was observed between apical and
      basolateral sides in the cells. RGE1-22 cells produced prostaglandin E(2). Levels
      of mRNA for cathepsin E, transepithelial resistance and prostaglandin E(2) were
      influenced by the nonpermissive temperature. Thus, these conditionally
      immortalized gastric cell lines which preserve some epithelial cell
      characteristics will provide a useful in vitro model of gastric epithelium.

PMID- 12207049
TI  - Identification of negative regulator of interleukin-3 (NIL-3) in bone marrow.
AB  - We have reported that an inhibitor of interleukin-3 (NIL-3) is produced from
      murine bone marrow cells in response to excess stimulation of interleukin-3. In
      this report, we attempted the purification of the NIL-3 activity from bone marrow
      culture supernatant in the presence of interleukin-3. The purified NIL-3 activity
      was a protein with relative molecular weight of 54.5 kDa (SDS-PAGE), which
      inhibited the growth of IL-3 dependent DA-1 cell growth in a dose dependent
      manner. The N-terminal amino acid sequence of purified NIL-3 activity was
      determined to be homologous to beta-2 glycoprotein I (apolipoprotein H: APO-H).
      The gene expression of APO-H was detected by nested-PCR in STIL-3 C5-CM
      stimulated total bone marrow cells and STIL-3 C5-CM stimulated bone marrow
      fraction 2 (Fr. 2) which has been reported as a hematopoietic stem cell rich
      fraction. These observations indicate the possibility that the APO-H is the NIL-3
      which was produced from bone marrow cells in response to excess IL-3 stimuli.

PMID- 12207050
TI  - Participation of host cell actin filaments during interaction of trypomastigote
      forms of Trypanosoma cruzi with host cells.
AB  - The involvement of actin filaments from the host cell on the process of invasion
      of trypomastigote forms of Trypanosma cruzi was analyzed in seven different cell
      lines. Prior incubation of all cell lines with cytochalasin D, under conditions
      which interfere with actin filaments, markedly inhibited parasite internalization
      and increased parasite attachment. Attached parasites were readily ingested
      following washing of the drug-treated cells. Cytochalasin treatment interfered
      with the distribution of actin filaments of the host cell as evaluated by
      visualization of the filaments using confocal laser scanning microscopy of cells
      incubated in the presence of FITC-phalloidin. Concentration of actin filaments
      could be observed in most, but not all, parasites in the process of
      internalization. We also treated LLCMK 2 and macrophage cells with
      Jasplakinolide, a drug that stabilizes actin filaments, before interaction with
      the trypomastigote forms. This drug partially inhibits parasite invasion into the
      cells. Prior incubation of the host cells in the presence of colchicine, which
      interfere with microtubules, also inhibited parasite internalization into the
      cells.

PMID- 12207051
TI  - Expression of selected apoptosis related genes, MIF, IGIF and TNF alpha, during
      retinoic acid-induced neural differentiation in murine embryonic stem cells.
AB  - Apoptosis plays an important role during embryonic development. Apoptotic cell
      death is executed by caspases and can be regulated by the Bcl-2 family of genes.
      Ribonuclease protection assay was used to investigate the expression of selected
      apoptosis-related genes of the Bcl-2 family, pro-apoptotic Bax, Bad and anti
      apoptotic Bcl-2, during differentiation of murine embryonic stem cells (ES)
      mediated by all-trans-retinoic acid. The mRNA expression of caspase 3, caspase 6
      and certain pro-inflammatory cytokines was also investigated simultaneously. ES
      cells exposed to 1 microM all-trans-retinoic acid on day 8, 9 and 10 of
      differentiation revealed increased expression of Bax and Bad compared to the
      vehicle-treated cells. No effect on Bcl-2 mRNA was noted after all-trans-retinoic
      acid treatment. Increased mRNA expression of caspase 3 and caspase 6 in all-trans
      retinoic acid-exposed ES cells suggested that caspases play an important role in
      retinoic acid-mediated apoptosis during ES differentiation. Increase in the
      expression of TNF alpha and macrophage migration inhibitory factor (MIF) was
      noted in retinoic acid-treated cells on day 14. Significant increase observed in
      interferon gamma inducing factor (IGIF/IL-18) mRNA expression in all-trans
      retinoic acid-treated cells on day 14 and 17 did not translate to increased INF
      gamma expression. No change in the expression of other pro-inflammatory cytokines
      was noted with all-trans-retinoic acid treatment. The function of TNF alpha,
      IGIF/IL-18 and MIF in all-trans-retinoic acid-treated cells during ES
      differentiation and apoptosis is still speculatory. Results suggested that RA
      mediated apoptosis during neural differentiation of ES cells involves up
      regulation of caspase 3, caspase 6, Bad, and Bax.

PMID- 12207052
TI  - Midkine expression is associated with postnatal development of the lungs.
AB  - A heparin-binding growth factor, midkine, is the product of a retinoic acid
      responsive gene. Since retinol plays critical roles in lung development and
      treatment of bronchopulmonary dysplasia, and midkine has been implicated in the
      maturation of lung explants and in cytoprotection, we herein examined midkine
      expression during postnatal development of the lungs and hyperoxic lung injury.
      Midkine protein transiently increased to a maximum level at around 4 days
      postnatal. Immunohistochemistry revealed that the amounts of midkine increased in
      resident alveolar cells, but not in smooth muscle cells or the large airway
      epithelium. If neonatal mice were exposed to >95% oxygen, lung development was
      impaired and midkine expression was suppressed. In contrast, when adult mouse
      lungs as well as in vitro cultured lung adenocarcinoma cells were exposed to
      hyperoxia, midkine expression was not affected. Furthermore, a pronounced
      induction of midkine by retinoic acid was observed in neonatal lungs. The results
      indicate that midkine expression is associated with postnatal lung development,
      but not necessarily with hyperoxic cell damage.

PMID- 12207053
TI  - Expression of Golgi membrane protein p138 is cell cycle-independent and
      dissociated from centrosome duplication.
AB  - In order to elucidate the mechanism controlling the biogenesis of the Golgi
      complex, we have studied whether the expression of a resident membrane protein
      p138 of the Golgi complex is dependent upon the cell cycle. The protein level of
      p138 in human KB cells was increased during thymidine block to synchronize the
      cells in the early-S phase, but changed little from S to G2 after release from
      the block. On the other hand, the mRNA level of the p138 gene was constant during
      the block. The change in mRNA level in the cells was small with a low peak at S
      to G2. Both p138 protein and mRNA levels decreased after cell division and then
      rose rapidly to the same level as those of log-phase cells in the next G1 to S.
      Thus, translation of p138 protein was upregulated in the cells at the early-S
      phase. However, we found also that the p138 protein level increased during an
      arrest at G2/M caused by etoposide. The kinetics of centrosome duplication
      apparently differ from those of p138 protein production. The duplication occurred
      mainly at S to G2 after the release from thymidine block, while the ratio of
      cells containing duplicated centrosomes increased gradually during the block.
      Taken together, these results show that both the translation and transcription of
      p138 protein are regulated independent of the cell cycle and dissociated from the
      duplication of the centrosome. Rather, the expression of p138 protein seems to be
      coupled with a change in cell size since both thymidine block and etoposide
      inhibition resulted in an apparent increase in cell size.

PMID- 12207054
TI  - Sexual selection, seminal coagulation and copulatory plug formation in primates.
AB  - This study examines the question of whether multipartner matings by female
      primates, with resulting sperm competition among males, may have favored the
      evolution of biochemical mechanisms to enhance seminal coagulationand copulatory
      plug formation. Comparative ratings of seminal coagulation (using a four-point
      scale where 1 = no coagulation and 4 = copulatory plug formation) were obtained
      for 40 species representing 26 primate genera. Coagulation ratings were highest
      (mean = 3.64) in those genera where females commonly mate with multiple partners,
      and lowest (mean = 2.09) in genera where females are primarily monogamous or
      belong to polygynous (one male) units(p < 0.0001). This result remained
      significant (p < 0.001) after the use of comparative analysis of independent
      contrasts (CAIC) to control for possible phylogenetic biases in the data set.
      Results indicate that sexual selection has played an important role in the
      evolution of seminal coagulation, and copulatory plug function, in primates.

PMID- 12207055
TI  - The functions of laryngeal air sacs in primates: a new hypothesis.
AB  - A possible function of laryngeal air sacs in apes and gibbons was investigated by
      examining the relationships between air sac distribution, call rate, call
      duration and body weight in a phylogenetic context. The results suggest that lack
      of sacs in the smaller gibbons and in humans is a derived feature. Call
      parameters in primates, such as rate and duration, scaled to resting breathing
      rate (and therefore to body weight) only in species without air sacs, which
      appear to modify these relationships. Apes and larger gibbons may be able to
      produce fast extended call sequences without the risk of hyperventilating because
      they can re-breathe exhaled air from their air sacs. Humans may have lost air
      sacs during their evolutionary history because they are able to modify their
      speech breathing patterns and so reduce any tendency to hyperventilate.

PMID- 12207056
TI  - Ranging behavior, group size and behavioral flexibility in Ethiopian hamadryas
      baboons (Papio hamadryas hamadryas).
AB  - This study reports group size, home range size, daily path lengths, seasonal
      effects on ranging behavior and qualitative information on diet for a population
      of hamadryas baboons inhabiting the lowlands of the northern Rift Valley in
      central Ethiopia. The minimum home range size and daily path length for this
      population are similar to those reported for other populations of hamadryas
      baboons in Ethiopia and Saudi Arabia. Group sizes, however, are much larger than
      those in most other hamadryas populations for which published data are available.
      The large group sizes in this area may be related to the abundance of one food
      resource in particular, doum palm nuts. Overall, this study suggests that
      hamadryas baboons may be more flexible in some aspects of their behavioral
      ecology (e.g. group size) than in others (e.g. ranging behavior).

PMID- 12207057
TI  - Duetting in the Titi monkey Callicebus cupreus: structure, pair specificity and
      development of duets.
AB  - Duets from a total of 6 female and 6 male titi monkeys (Callicebus cupreus) were
      analysed in order to provide an in-depth analysis of the duet structure, to
      investigate whether duets are pair specific and to examine whether duets of newly
      formed pairs differ from those of established pairs. Callicebus duets are
      composed of alternately uttered male and female contributions. Duets were pair
      specific as a result of a summation of individual attributes of the two mates
      rather than due to unidirectional or reciprocal song adaptation by mates. The two
      examined newly formed pairs produced species-typical duets from the first day on,
      but their duets showed greater variability in sequence durations than those of
      established pairs.

PMID- 12207058
TI  - Past and present distribution of the red-bellied monkey Cercopithecus
      erythrogaster erythrogaster in Benin.
AB  - This study provides data on the past and present distribution of the red-bellied
      monkey, Cercopithecus erythrogaster erythrogaster, a subspecies that is endemic
      to Benin's southern ecosystems. The original distribution of this subspecies was
      between the Couffo River and the Nigerian border, but it has since been reduced
      to regions degraded by intense human settlement (such as the Oueme river valley)
      and to some better preserved areas, such as the Lama protected forest and some
      sacred grove forests in wet areas. Local people participated in this research
      programme and, as a result, many new localities have been discovered. All of
      these have been in wetlands in southern Benin, mainly in sacred groves.
      Conservation action for this subspecies will succeed only if local people are
      involved in its protection.

PMID- 12207059
TI  - Acoustic differences between spontaneous and induced long calls of golden lion
      tamarins, Leontopithecus rosalia.
AB  - Long calls are emitted by several primate taxa and appear to have multiple
      functions related to spacing mechanisms and reproduction. Yet, in some species
      the spontaneous rate of emission of these calls is low, and playbacks are used to
      elicit long calls to augment the sample size of studies. The objective of this
      study was to compare the acoustic structure of spontaneously emitted and
      experimentally induced long calls of golden lion tamarins. Results from 6 adult
      tamarins show that spontaneously emitted long calls differ acoustically from
      experimentally induced long calls in several frequency measures. Several
      explanations for these differences are discussed. We conclude that regardless of
      the underlying mechanisms, playbacks elicit responses that may be different from
      naturally occurring calls.

PMID- 12207060
TI  - Individual distinctiveness of the contact calls of ring-tailed lemurs.

PMID- 12207061
TI  - Drinking observations in Temminck's red colobus.

PMID- 12207062
TI  - Negative reinforcement in primate societies related to aggressive restraint.

PMID- 12207063
TI  - Sifaka predation by a large boa.

PMID- 12207064
TI  - Boa constrictor attack and successful group defence in moustached tamarins,
      Saguinus mystax.

PMID- 12207066
TI  - Clinical potential of biological response modifiers combined with chemotherapy
      for gastric cancer. Japanese experience.
AB  - The most effective treatment for gastric cancer is complete surgical resection
      with lymphadenectomy. However, a number of patients experience recurrence of the
      cancer even after curative surgery. This review focuses on comparative trials
      studying the use of adjuvant therapy with chemotherapy plus immunotherapy in the
      treatment of patients with curatively resected gastric cancer. Preoperative and
      intraperitoneal therapy, and therapy for advanced or recurrent gastric cancer are
      also discussed. At present, some subset analyses of adjuvant trials have shown
      favorable results suggesting that the biological response modifiers (BRMs), PSK
      or OK-432, add a benefit to chemotherapy. For advanced gastric cancer, although
      gastric cancer cells are generally not very sensitive to most of the currently
      available chemotherapeutic agents, it has been reported that biochemical
      modulation with treatments including low-dose cisplatin + 5-FU (fluorouracil)
      have high response rates and exert an immunomodulatory effect especially when
      used in combination with BRMs. The impact of splenectomy and some of the
      promising newly developed drugs are discussed.

PMID- 12207067
TI  - Aboral pouch with preserved duodenal passage--new reconstruction method after
      total gastrectomy.
AB  - A new reconstruction method--the aboral pouch with preserved duodenal passage-
      has been introduced after total gastrectomy. After removal of the stomach,
      preparation of the Roux loop and construction of the esophago-jejunostomy, a
      jejuno-duodenostomy is performed approximately 50 cm away from the esophageal
      anastomosis between the Roux limb and the duodenal stump. Right below this second
      anastomosis, the Roux limb is closed with a stapling device to provide a
      unidirectional food passage through the duodenum. The aboral pouch is constructed
      as a side-to-side anastomosis between the Roux limb under the stapled segment and
      the aboral end of the Y limb. The advantages of the reservoir-constructing
      methods and the interposition methods are combined in this new reconstruction
      type. Our experiences of 17 cases having undergone this reconstruction method are
      presented.

PMID- 12207068
TI  - Metastatic hepatocellular carcinoma of the gallbladder.

PMID- 12207069
TI  - Results of surgical therapy of adenocarcinomas of the esophagogastric junction
      according to a standardized surgical resection technique.
AB  - AIM: The aim of this retrospective analysis was to exclusively present the
      surgical results of patients with type-I-III adenocarcinomas of the
      esophagogastric junction thereby providing a basis for comparison with other
      approaches. METHODS: 56 patients with Barrett's carcinomas and 74 patients with
      cardial and subcardial tumors were operated on and evaluated. The surgical
      procedure for type-II/III carcinomas was identical: total gastrectomy,
      omentectomy and splenectomy with lymph node dissection after a combined left
      thoraco-abdominal incision. Both tumor entities were summarized into 1 group and
      compared with the results of surgery for Barrett's carcinomas: subtotal
      esophagectomy and proximal stomach resection with lymph node dissection after
      right thoracotomy and an additional abdominal incision. RESULTS: In 93% of all
      patients an R0 resection was possible. In patients with Barrett's carcinomas
      pulmonal complications (41%) were the predominant postoperative problems. The 30
      day lethality (5.3%) was higher in the group of patients with type-I carcinomas
      compared to those with type-II/III carcinomas (1.4%). Tumor infiltration and
      nodal involvement determined the prognosis after R0 resection. The presence of
      Barrett's mucosa in type-I adenocarcinomas and the histological assessment
      according to Lauren's classification into type-II/III carcinomas also influenced
      the long-term prognosis. CONCLUSION: After R0 resection it is not the tumor
      location but tumor infiltration, lymph node status and a differentiated
      histological assessment that determine the prognosis of patients with
      adenocarcinomas of the esophagogastric junction.

PMID- 12207070
TI  - Early surgical correction for isolated gastric stricture following acid corrosion
      injury.
AB  - OBJECTIVE: To evaluate the feasibility and long-term results of early gastric
      surgery for patients with isolated gastric stricture following acid corrosion
      injury. MATERIALS AND METHODS: Upper gastrointestinal (UGI) series was routinely
      performed around the 4th week after acid corrosion injury. Patients with gastric
      stricture and no risk of delayed esophageal stricture underwent early solitary
      gastric surgery, which was defined when performance of the procedure took place
      within 2 months of the injury. RESULTS: From June 1988 to June 2000, 35 of 378
      patients with acid corrosion injury developed isolated gastric stricture. Twenty
      four (68.6%) lesions were located in the antrum, and 11 (31.4%) in the gastric
      body. Postprandial vomiting presented earlier for the antral stricture group
      (17.6 +/- 1.1 versus 25.4 +/- 3.4 days after injury; p = 0.005). The UGI series
      was performed from 16 to 41 days after injury (average 25 days). Of the 35 acid
      corrosion injury patients in this study, 4 were excluded because of late
      referrals to our institution or the patient's hesitation which resulted in
      delayed surgery. The remaining 31 patients underwent gastric surgery 35.7 +/- 3.2
      days after ingestion (34.6 +/- 3.6 and 38.1 +/- 3.4 days for cases of antral and
      gastric body stricture, respectively). Surgical procedures consisted of
      hemigastrectomy (n = 16), antrectomy (n = 2), gastroenterostomy (n = 2), subtotal
      gastrectomy (n = 6), and total gastrectomy (n = 5). There were 4 cases of
      postoperative complications (12.9%) including adhesion ileus (n = 2), wound
      infection (n = 1), and massive, postoperative UGI bleeding (n = 1). Surgical
      mortality was zero. All patients tolerated oral intake well after surgery. During
      the minimum follow-up period of 1 year, 1 patient developed esophagojejunostomy
      stenosis, which was resolved by dilation, and there was 1 case of dumping
      syndrome, which was treated by diet control. CONCLUSION: Early surgery correction
      is feasible and safe if patients with isolated gastric stricture following acid
      corrosion injury are carefully selected. All patients in our study recovered
      early, with a low morbidity rate.

PMID- 12207071
TI  - Results of combined gastrectomy and pancreatic resection in patients with
      advanced primary gastric carcinoma.
AB  - BACKGROUND/AIMS: Although the incidence of primary gastric carcinoma is
      decreasing, the majority of patients in Western countries are still diagnosed
      with advanced tumor stages. In many cases surgical therapy can be performed only
      by multivisceral resections including the pancreas. METHODS: Between April 1986
      and April 1997, thirty-three patients with primary gastric carcinoma underwent
      gastric resection and segmental/total pancreatectomy at our institution (21
      males, 12 females; median age 57 years). The operative and pathologic findings
      and clinical course in these patients were analyzed retrospectively. RESULTS: In
      all patients total gastrectomy with D2 lymphadenectomy was performed. In 26
      patients (79%) the pancreatic tail was also resected. Other resections included
      the pancreatic head in 5 patients (15%) and the whole pancreas in 2 cases (6%).
      Radical (R0) resections were possible in 73% of all cases (n = 24). 22 patients
      (67%) had stage-IV disease due to liver/peritoneal metastases (n = 11) or to
      extensive lymph node metastases (N3, n = 11). Histology showed a predominance of
      the diffuse type according to Lauren (n = 16, 49%). Intraoperatively suspected
      tumor infiltration of the pancreas was confirmed by histology only in 39% (n =
      13) of the examined resection specimens. Postoperative morbidity was 36% (n = 12)
      and mortality was 9% (n = 3). Five patients developed pancreatitis or
      peripancreatic abscess, 2 with a lethal outcome. Overall the median survival was
      13 months. Following R0 resection median survival was 17 months. If the pancreas
      was microscopically not infiltrated, median survival was 23 months. CONCLUSION:
      Pancreatic invasion in patients with gastric carcinoma is often associated with
      positive lymph nodes and liver metastases or peritoneal carcinomatosis.
      Intraoperatively, true pancreas invasion is difficult to differentiate from
      inflammatory reactions. Postoperative morbidity and mortality are increased by
      pancreatic resection, mainly due to pancreatitis or peripancreatic abscess.
      Curative (R0) resection improves prognosis and even long-term survival can be
      achieved in selected individual cases. Palliative resections can be performed for
      local complications like bleeding or obstruction refractory to other therapies.

PMID- 12207072
TI  - Clinicopathologic features of mucinous gastric carcinoma.
AB  - BACKGROUND/AIMS: Mucinous gastric carcinoma (MGC) is a histopathologic subtype of
      gastric carcinoma with a poor prognosis. The purpose of this study was to compare
      the disease course of MGC with non-mucinous gastric carcinoma (NMGC) and study
      the clinicopathologic features that influence the prognosis of MGC patients.
      METHODS: We reviewed the records of 2,383 patients with a confirmed histologic
      diagnosis of gastric carcinoma. There were 157 patients with MGC compared to
      2,226 with NMGC. RESULTS: A depth of invasion greater than T3 was more frequently
      found in MGC than in NMGC. The mean number of lymph nodes with metastases was
      2.78 in MGC and 2.28 in NMGC (p < 0.001). There were more MGC patients with TNM
      stages II through IV (UICC classification). The overall survival rate was lower
      for the MGC group (46.5%) than for the NMGC group (64.0%; p < 0.05). Depth of
      invasion, lymph node metastases, and stage at diagnosis were significant factors
      affecting the outcome. CONCLUSION: The factors influencing the poorer prognosis
      (lower 5-year survival rate) of MGC are the advanced stage at the time of
      diagnosis, lymph node metastases, and a higher TNM status. Mucinous histologic
      type itself was not an independent predictive factor in survival.

PMID- 12207073
TI  - Pancreatic injury in severe trauma: early diagnosis and therapy improve the
      outcome.
AB  - BACKGROUND: Pancreatic injury is a dangerous complication in multiple injury, and
      experience with its diagnosis and treatment is usually limited. METHOD:
      Retrospective analysis of 3,840 patients admitted after multiple trauma from
      January 1, 1982, until May 31, 2000. RESULTS: A laparotomy was performed in 121
      cases (3.15%) due to suspected intra-abdominal lesion. 32% of the patients
      (39/121) had a pancreatic lesion; 23% (9/39) had a rupture of the major
      pancreatic duct. Primary laparotomy was performed in 72% of the patients (28/39).
      Superficial lesions were treated by explorative laparotomy alone (n = 7),
      debridement and external drainage (n = 20), or necrosectomy and lavage (n = 3).
      Complex pancreatic lesions were treated by pancreatojejunostomies (n = 5),
      pancreatic left resections (n = 2), or exploration alone (n = 2). 8 of 39
      patients died (20%), 4 intraoperatively. Of the surviving 35 patients, a pancreas
      associated complication developed in 8 patients (23%): pancreatic abscesses (n =
      4), traumatic pancreatitis (n = 3), pancreatic fistulas (n = 2), and pseudocysts
      (n = 2). CONCLUSIONS: Pancreatic injury is an infrequent but dangerous
      complication in severe trauma. Superficial lesions not affecting the major
      pancreatic duct can be managed by debridement and external drainage. If the major
      pancreatic duct is ruptured, organ-preserving, complex reconstructive procedures
      are necessary. When diagnosed timely and treated according to severity and
      overall situation, pancreatic injuries have an acceptable morbidity, but usually
      a high mortality.

PMID- 12207074
TI  - Influence of a human protease inhibitor on surgical stress induced
      immunosuppression.
AB  - BACKGROUND/AIM: Postoperative tissue injury and immunosuppression can occur after
      major surgery. In this study, we explore the potential benefits of administering
      a protease inhibitor to treat immunosuppression caused by surgical stress.
      METHODS: Sixteen patients with esophageal cancer were preoperatively allocated at
      random into two equal groups. A urinary trypsin inhibitor, ulinastatin (UTI), was
      intravenously administered to the treatment (UTI) group at a dose of 150,000 U
      every 12 h from the start of surgery until postoperative day 5, whereas the
      control group received a placebo. One unit of UTI was defined as the amount of
      UTI necessary to inhibit the activity of 2 microg of bovine pancreatic trypsin by
      50%. We measured the plasma levels of polymorphonuclear neutrophil elastase,
      interleukin 8, circulating T lymphocyte subsets, and mitogenic activity and in
      vitro production of tumor necrosis factor alpha in lipopolysaccharide-stimulated
      whole blood. RESULTS: The postoperative serum value of polymorphonuclear
      neutrophil elastase was significantly lower in the UTI group, but the interleukin
      8 concentrations did not significantly vary between the two groups. On the other
      hand, the severity of the postoperative immunosuppression was reduced in the UTI
      group, and immune functions, such as the numbers of T lymphocytes, the mitogenic
      activity of lymphocytes, and the level of tumor necrosis factor alpha production
      in whole blood, recovered significantly earlier in the UTI group. CONCLUSION:
      These data suggest that a protease-modulating therapy may be a new strategy for
      the treatment of surgical stress induced immune dysfunction.

PMID- 12207075
TI  - Could honey have a place in colitis therapy? Effects of honey, prednisolone, and
      disulfiram on inflammation, nitric oxide, and free radical formation.
AB  - BACKGROUND/AIMS: The purpose of this study was to investigate the potential
      therapeutic roles of honey, prednisolone and disulfiram in an experimental model
      of inflammatory bowel disease. Another aspect of the study was to find out
      whether these substances have any effect on nitric oxide (NO) and free radical
      production. METHODS: After the induction of colitis with trinitrobenzene sulfonic
      acid in 64 male rats, physiological saline, honey, prednisolone and disulfiram
      enemas were applied to the rats once daily for 3 days (acute treatment groups) or
      7 days (chronic treatment groups). Control groups received only saline enemas.
      Rats were killed on the 4th or 8th days and their colonic mucosal damage was
      quantitated using a scoring system. Acute and chronic inflammatory responses were
      determined by a mucosal injury score, histological examination and measurement of
      the myeloperoxidase (MPO) activity of tissues. The content of malonylaldehyde
      (MDA) and NO metabolites in colon homogenates was also measured to assess the
      effects of these substances on NO and free oxygen radical production. RESULTS:
      Estimation of colonic damage by mucosal injury scoring was found to be strongly
      correlated with the histologic evaluation of colon specimens. On the other hand,
      mucosal injury scores were not correlated with MPO, MDA or NO values. There were
      significant differences between the MPO results of chronic-control and chronic
      honey groups, as well as chronic-control and chronic-prednisolone groups (p =
      0.03 and p = 0.0007). The acute honey, prednisolone, and disulfiram groups had
      significantly lower MDA results compared to the acute control group (p = 0.04, p
      = 0.02, and p = 0.04). In terms of NO, there was no significant difference
      between the treatment and control groups. NO was found to have a strong
      relationship with MDA (p = 0.03) and MPO values (p = 0.001). On the other hand,
      MPO results were not found to be correlated with MDA values (p > 0.05).
      CONCLUSIONS: MPO activity is not directly proportional to the severity of the
      inflammation, but it may only determine the amount of neutrophil in the tissues.
      Inflammatory cells are not the sole intensifying factor in colitis. Therefore,
      mucosal injury scores may not correlate well with MPO activities. In an
      inflammatory state NO and MPO levels have a strong relationship, since NO is
      released from the neutrophils. In an inflammatory model of colitis, intrarectal
      honey administration is as effective as prednisolone treatment. Honey may have
      some features in the treatment of colitis, but this issue requires further
      investigation. Honey, prednisolone and even disulfiram also have some value in
      preventing the formation of free radicals released from the inflamed tissues.
      Prednisolone may also have some possible benefits in the inhibition of NO
      production in colitis therapy.

PMID- 12207076
TI  - Jan Mikulicz-Radecki (1850-1905)--the creator of modern European surgery.

PMID- 12207077
TI  - Massive bleeding from Dieulafoy's lesion of the small intestine in a child-
      therapy for the bleeding from gastrointestinal tract out of endoscopic
      observation.
AB  - Dieulafoy's lesion is recognized as a submucosal artery associated with a minute
      mucosal defect and a rare cause of severe gastrointestinal hemorrhage.
      Especially, that of distal jejunum or ileum is extraordinarily rare. It is very
      difficult to detect the lesion in these parts. We experienced massive bleeding
      from Dieulafoy's lesion of the distal jejunum in a 12-year-old girl. Preoperative
      angiography and intraoperative palpation detected the point of bleeding. She was
      rescued by partial jejunectomy. Compiled reports suggested that careful palpation
      was useful for detection of the location of the bleeding point, which was
      enhanced as vascular dilatation by the angiogram, during the operation
      comparatively.

PMID- 12207078
TI  - Mucin-secreting bile duct adenoma--clinicopathological resemblance to intraductal
      papillary mucinous tumor of the pancreas.
AB  - We describe a case of mucin-secreting biliary adenoma associated with obstructive
      jaundice due to mucin production. Duodenal endoscopy revealed mucin secretion
      through an enlarged papilla of Vater. On the cholangiogram, large filling defects
      caused by mucin were observed in the dilated bile duct. Granular and/or papillary
      mucosa was noted from the hilar to the common bile duct by using percutaneous
      transhepatic cholangioscopy. Biopsy specimens taken from the papillary mucosa
      revealed slightly papillary projection without any evidence of malignancy. This
      lesion was diagnosed as mucin-secreting superficial adenoma and
      pancreatoduodenectomy was performed according to the malignant behavior. Using a
      histologic examination of the specimen, pure adenoma was documented. Since the
      surgical margin was positive, radiation was added for the residual adenoma in the
      intrahepatic bile ducts. The patient has been well without any evidence of
      recurrence for 21 months since her operation. It is only recently that the term
      'intraductal papillary mucinous tumor (IPMT)', which is accepted as a distinct
      disease entity of pancreas, has begun to be used for mucin-secreting bile duct
      tumor. This case also seemed to clinicopathologically resemble an IPMT of the
      pancreas.

PMID- 12207079
TI  - Sigmoidoscopy-assisted colostomy--an adapted trephine stoma formation.
AB  - BACKGROUND/AIM: The purpose of this article was to report an adapted colostomy
      procedure that can be used on patients with multiple morbidities requiring fecal
      diversion. METHODS: An adapted colostomy was performed on a patient needing fecal
      diversion who had multiple surgical and medical complications. RESULTS: Thirteen
      weeks after colostomy placement, the patient's colostomy functioned well and was
      viable throughout his course without related complications. CONCLUSION: The
      method of sigmoidoscopy-assisted colostomy described here can be beneficial to
      the complicated patient needing fecal diversion but unable to tolerate a
      laparotomy or laparoscopy.

PMID- 12207080
TI  - Convergence: obstacle or opportunity?

PMID- 12207081
TI  - Evolutionary convergence in nervous systems: insights from comparative
      phylogenetic studies.
AB  - Over the past 20 years, cladistic analyses have revolutionized our understanding
      of brain evolution by demonstrating that many structures, some of which had
      previously been assumed to be homologous, have evolved many times independently.
      These and other studies demonstrate that evolutionary convergence in brain
      anatomy and function is widespread. Although there are relatively few
      neuroethological studies in which brain and behavior have be studied within an
      evolutionary framework, three relatively well studied cases are reviewed here:
      electric communication among gymnotiform and mormyriform fishes, prey capture
      among frogs, and sound localization among owls. These three examples reveal
      similar patterns of brain evolution. First, it is clear that novel abilities have
      evolved many times independently in taxa whose common ancestors lack these
      abilities. Second, it is apparent that small changes in neural pathways can lead
      to dramatic changes in an organism's abilities. Brain evolution at this small
      scale is quite common. The behavioral importance of small scale changes on one
      hand, and the pervasiveness of convergent evolution on the other, have several
      implications for understanding brain evolution. First, similar abilities may be
      conferred by convergent rather than homologous circuits, even among closely
      related species. Furthermore, closely related species may use the same
      information in different ways, or they may use different means to obtain the same
      information. One reason that convergence is so common in the biological world may
      be that the evolutionary appearance of novel functions is associated with
      constraints, for example in the algorithms used for a given neural computation.
      Convergence in functional organization may thus reveal basic design features of
      neural circuits in species that possess unique evolutionary histories but use
      similar algorithms to solve basic computational problems.

PMID- 12207082
TI  - Convergent evolution on the molecular level.
AB  - Divergence and convergence are two evolutionary processes by which organisms
      become adapted to their environments. With the advent of molecular biological
      techniques it is possible to ask if these processes are observed at the molecular
      level. There are many examples of molecular divergence in which molecular
      sequence or function change over evolutionary time. There are fewer reports of
      convergent evolution on the molecular level, and these claims are sometimes
      controversial. In this paper I discuss the types of convergent molecular
      evolution, describe the criteria for accepting or rejecting convergence, and give
      some examples relevant to neurobiology where convergence has been claimed. These
      include convergent evolution of opsins, gap junction proteins, neurotransmitter
      receptors, ion channels, and venoms directed against ion channels.

PMID- 12207083
TI  - Convergences in the modular and areal organization of the forebrain of mammals:
      implications for the reconstruction of forebrain evolution.
AB  - Early efforts to reconstruct the course of the evolution of the human brain
      relied on comparing the brains of a few related mammals with brains at
      successively higher levels of complexity. This Clark or ladder of levels approach
      is now seen as having limited usefulness in that species are not easily assigned
      to levels, and extant mammals are now recognized as mosaics of primitive and
      derived features. In addition, direction of change does not necessarily proceed
      from simple to complex, small to large, or diffuse to differentiated. A modern
      cladistic approach reconstructs the brains of ancestors by identifying brain
      characters within and across phylogenetic groups (clades), and uses parsimony or
      likelihood to infer direction of change and distinguish ancestral features from
      independently evolved convergences. Unfortunately, an idealized cladistic
      approach is often difficult to realize because characters may be hard to identify
      and validate, key species may be unavailable for study, and broadly based
      comparative studies can be costly, poorly funded, and labor intensive. Thus, many
      investigators pursue a truncated approach that is superficially Clark-like but
      conceptually cladistic. A truncated approach that relies on the extensive study
      of a few species may compensate for weaknesses by including niche-matched species
      that offer the opportunity to estimate the likelihood of similar brain features
      evolving as convergent adaptations. Because inferences about the brains of the
      primate ancestor are often made from the brains of tree shrews, we compare the
      brains of squirrel-like tree shrews with the brains of diurnal squirrels, and
      suggest that many of the primate-like features of the visual system of tree
      shrews arose independently of those in primates.

PMID- 12207084
TI  - Why are olfactory systems of different animals so similar?
AB  - As we learn more about the neurobiology of olfaction, it is becoming increasingly
      clear that olfactory systems of animals in disparate phyla possess many striking
      features in common. Why? Do these features provide clues about the ways the
      nervous system processes olfactory information? This might be the case if these
      commonalities are convergent adaptations that serve similar functions, but
      similar features can be present in disparate animals for other reasons. For
      example, similar features may be present because of inheritance from a common
      ancestor (homology), may represent responses to similar constraints, or may be
      superficial or reflect strategies used by researchers studying the system. In
      this paper, I examine four examples of features of olfactory systems in members
      of different phyla: the presence of odorant binding proteins in the fluid
      overlying olfactory receptor neurons; the use of G protein-coupled receptors as
      odorant receptors; the use of a two-step pathway in the transduction of odorant
      signals; and the presence of glomerular neuropils in the first central target of
      the axons of olfactory receptor cells. I analyze data from nematodes, arthropods,
      molluscs, and vertebrates to investigate the phylogenetic distribution of these
      features, and to try to explain the presence of these features in disparate
      animals. Phylogenetic analyses indicate that these features are not homologous
      across phyla. Although these features are often interpreted as convergent
      adaptations, I find that alternative explanations are difficult to dismiss. In
      many cases, it seems that olfactory system features that are similar across phyla
      may reflect both responses to similar constraints and adaptations for similar
      tasks.

PMID- 12207085
TI  - Evolutionary convergence and shared computational principles in the auditory
      system.
AB  - Precise temporal coding is a hallmark of the auditory system. Selective pressures
      to improve accuracy or encode more rapid changes have produced a suite of
      convergent physiological and morphological features that contribute to temporal
      coding. Comparative studies of temporal coding also point to shared computational
      strategies, and suggest how selection acts to improve coding. Both the avian
      cochlear nucleus angularis and the mammalian cochlear nuclei have heterogeneous
      cell populations, and similar responses to sound. These shared characteristics
      may represent convergent responses to similar selective pressures to encode
      features of airborne sound.

PMID- 12207086
TI  - Evolution of cerebellum-like structures.
AB  - All vertebrate brains have a cerebellum, and most of them have one or more
      additional structures that are histologically similar to the cerebellum. The
      cerebellum-like structures include the medial octavolateral nucleus in most
      aquatic vertebrates; the dorsal octavolateral nucleus in many aquatic vertebrates
      with an electrosensory system; the marginal layer of the optic tectum in ray
      finned fishes; electrosensory lobes in the few groups of advanced bony fish with
      an electrosensory system; the rostrolateral nucleus of the thalamus in a few
      widely scattered groups of bony fish; and the dorsal cochlear nucleus in all
      mammals except monotremes. All of these structures receive topographically
      organized sensory input in their deep layers. Purkinje-like cells receive the
      sensory input near their cell bodies. These cells extend apical dendrites up into
      the molecular layer where they receive synaptic input from parallel fibers. The
      cerebellum itself can be included within this characterization by considering the
      climbing fiber as at least in part a conveyor of sensory information and by
      recalling that climbing fibers in more basal vertebrates terminate on smooth
      dendrites close to the soma. Physiological findings from three different systems
      suggest the hypothesis that cerebellum-like structures remove predictable
      features from the sensory inflow. Phylogenetic homology can explain the
      similarities across different taxa for some types of cerebellum-like structures,
      but similarities within other types cannot be explained in this way. Moreover,
      phylogenetic homology cannot explain the similarities among different types of
      cerebellum-like structures. Evolutionary convergence provides the best
      explanation for all these similarities that cannot be explained by homology. The
      convergence is almost surely constrained by the availability of a genetic
      developmental program for creating cerebellum-like circuitry and by the need
      within many different systems for the type of information processing that
      cerebellum-like circuitry can provide.

PMID- 12207087
TI  - Do convergent developmental mechanisms underlie convergent phenotypes?
AB  - Convergence is a pervasive evolutionary process, affecting many aspects of
      phenotype and even genotype. Relatively little is known about convergence in
      developmental processes, however, nor about the degree to which convergence in
      development underlies convergence in anatomy. A switch in the ecology of sea
      urchins from feeding to nonfeeding larvae illustrates how convergence in
      development can be associated with convergence in anatomy. Comparisons to more
      distantly related taxa, however, suggest that this association may be limited to
      relatively close phylogenetic comparisons. Similarities in gene expression during
      development provide another window into the association between convergence in
      developmental processes and convergence in anatomy. Several well-studied
      transcription factors exhibit likely cases of convergent gene expression in
      distantly related animal phyla. Convergence in regulatory gene expression domains
      is probably more common than generally acknowledged, and can arise for several
      different reasons.

PMID- 12207089
TI  - From erythropoietin to oxygen: hypoxia-inducible factor hydroxylases and the
      hypoxia signal pathway.
AB  - The regulation of blood red cell production by the hormone erythropoietin (Epo)
      provides a paradigm for control of gene expression by oxygen. Analysis of this
      pathway has revealed a widespread system of gene regulation based on a
      transcriptional complex termed hypoxia-inducible factor (HIF). Hydroxylation of
      specific prolyl and asparinyl residues in the alpha subunit of HIF by a series of
      non-haem iron-dependent dioxygenases has been defined as a novel mechanism of
      protein modification that transduces the oxygen-sensitive signal.

PMID- 12207090
TI  - Uremia-specific alterations in lipid metabolism.
AB  - Uremic patients suffer from a secondary form of complex dyslipidemia consisting
      of quantitative and qualitative abnormalities in serum lipoproteins resulting in
      altered lipoprotein composition and metabolism. The most prominent are an
      increase in serum triglyceride levels (due to elevated very-low-density
      lipoprotein remnants and intermediate-density lipoprotein) and low high-density
      lipoprotein (HDL) cholesterol. Low-density lipoprotein (LDL) cholesterol is often
      normal, but the cholesterol may originate from the atherogenic small and dense
      LDL subclass. The apolipoprotein B-containing part of the lipoprotein may undergo
      modifications (peptide modification of the enzymatic and advanced glycation end
      product, oxidation or glycosylation). Modifications contribute to impaired LDL
      receptor-mediated clearance from plasma and promote prolonged circulation. HDL
      particles are structurally altered during states of inflammation. The
      contribution of this complex and atherogenic form of dyslipidemia to
      cardiovascular disease in patients with renal disease is at present unclear. Most
      studies are negative in demonstrating the predictive power of serum lipids for
      the development of cardiovascular disease. This is most likely due to
      interference with deteriorating aspects of the activated acute-phase response.
      Since it is also still unclear whether we have therapeutics available with a
      sufficient impact on LDL size, remnant lipoprotein lowering and restoration of
      HDL function, we urgently need specific intervention trials.

PMID- 12207091
TI  - Inflammation, malnutrition and atherosclerosis in end-stage renal disease: a
      global perspective.
AB  - End-stage renal disease (ESRD) is characterized by an exceptional cardiovascular
      mortality rate. Although traditional risk factors are common in ESRD patients,
      they alone may not be sufficient to account for the high prevalence of
      cardiovascular disease (CVD). Recent evidence demonstrated that chronic
      inflammation, a non-traditional risk factor which is commonly observed in ESRD
      patients, may cause malnutrition and progressive atherosclerotic CVD by several
      pathogenetic mechanisms. Although both malnutrition and inflammation have been
      shown to be strong predictors of cardiovascular mortality in ESRD patients, it
      must be remembered that the majority of studies describing the presence of
      inflammation and malnutrition have been performed in Western and Asian
      industrialized countries. As it is evident that the prevalence of malnutrition
      and inflammation may differ markedly between different regions of the world and
      developing countries face a much higher prevalence of chronic infectious
      diseases, comparative inter-regional studies focusing on the etiology and
      prevalence of the malnutrition, inflammation and atherosclerosis syndrome are
      warranted.

PMID- 12207092
TI  - Endothelial dysfunction in uraemia.
AB  - Cardiovascular disease is a major cause of morbidity and mortality in chronic
      renal failure (CRF). The endothelium plays a central role in the control of many
      aspects of vascular function, and abnormalities may contribute to the generation
      of atherosclerosis. The endothelium produces a wide range of regulatory molecules
      which, in health, function in concert to provide a carefully balanced anti
      atherogenic environment. Endothelial dysfunction has been repeatedly demonstrated
      in renal failure, is present in the absence of anatomically obvious disease and
      appears to be useful in the prediction of morbidity and mortality in other
      cardiovascular risk groups. One of the most intensively studied and important
      mediators of endothelial function is nitric oxide (NO), whose production is
      reduced in CRF. A number of possible mechanisms for reduced NO bioavailability
      have been investigated including substrate limitation, competitive inhibition of
      NO synthase by endogenous NO synthase inhibitors known to accumulate in renal
      failure, and premature quenching of NO by free radicals present in high
      concentrations in this group. A clearer understanding of the pathogenesis of
      endothelial dysfunction in CRF has potential clinical implications. It may
      provide avenues for therapeutic interventions before the onset of clinically
      obvious cardiovascular disease in this high-risk patient group.

PMID- 12207093
TI  - Cardiovascular changes in renal failure.
AB  - In patients with renal failure cardiovascular complications are an important
      clinical problem and cardiac death is the main cause of death in these patients.
      It is well documented that cardiac risk is increased by a factor of 20 in uremic
      patients compared with age- and sex-matched segments of the general population.
      This finding in patients with renal failure can be at least partially explained
      by the well-described structural and metabolic abnormalities of the myocardium.
      The present article focuses on the structural changes in the heart and the
      vasculature and their potential repercussions for cardiovascular function, in
      particular their contribution to the high cardiovascular morbidity and mortality
      in patients with renal failure.

PMID- 12207094
TI  - Relationship between salt intake, nitric oxide and asymmetric dimethylarginine
      and its relevance to patients with end-stage renal disease.
AB  - Patients with essential hypertension (n = 24) were administered a low-salt diet
      (2 g NaCl/day), a high-salt diet (20-23 g) and then a low-salt diet for 7 days,
      and plasma levels of nitrate and nitrite (NOx) and asymmetric dimethylarginine
      (ADMA) were examined. There was a negative correlation between the percent
      changes in mean blood pressure and the plasma NOx concentration after salt
      loading and restriction. The percent change in plasma ADMA concentration was
      negatively correlated with that in the plasma NOx concentration after salt
      loading and restriction. In patients with end-stage renal disease (n = 51), the
      plasma ADMA concentration was positively correlated with the duration of dialysis
      treatment. The frequency of cardiovascular events was greater in patients with a
      plasma ADMA level of >/=3 microM than in those with a plasma AMDA level of <3
      microM. The results indicate that ADMA is not only a modulator of salt
      sensitivity in hypertension but also a cardiovascular risk factor in end-stage
      renal disease.

PMID- 12207095
TI  - Endothelial damage, asymmetric dimethylarginine and cardiovascular risk in end
      stage renal disease.
AB  - To be appropriately labelled as a 'risk factor' any putative risk factor should
      increase the prediction power of standard statistical models based on
      'traditional' (Framingham) risk factors. In end-stage renal disease (ESRD),
      Framingham risk factors do not fully explain the cardiovascular burden of these
      patients. Inflammation, hyperhomocysteinemia and anemia contribute to the high
      cardiovascular risk of ESRD, but knowledge is still incomplete. We suspected that
      asymmetric dimethylarginine (ADMA) is an important cardiovascular risk factor in
      dialysis patients. This substance inhibits nitric oxide synthase thus triggering
      a series of pathophysiological events leading to atherosclerosis. To test this
      hypothesis, we studied the relationship between ADMA and intima media thickness
      (IMT) in the carotid artery. ADMA was found to be strongly and independently
      related to IMT. More importantly we found that patients with relatively higher
      plasma ADMA had shorter survival and a higher rate of incident cardiovascular
      complications in comparison to those with a relatively lower plasma
      concentration. These data represent a sound basis for intervention studies aimed
      at modifying the plasma ADMA concentration in ESRD patients.

PMID- 12207096
TI  - Novel insights into uremic vascular calcification: role of matrix Gla protein and
      alpha-2-Heremans Schmid glycoprotein/fetuin.
AB  - Cardiovascular mortality is markedly increased in the dialysis population when
      compared to non-uremic subjects. Vascular and valvular calcifications are most
      frequently found in dialysis patients at risk and are independent predictors of
      cardiovascular death in this population. Traditionally, the presence of
      hyperphosphatemia and an increased calcium x phosphate product was considered a
      major pathomechanistic condition leading to excessive vascular and soft-tissue
      calcifications in uremic subjects. Recent studies in knockout mice, however,
      revealed that deficiencies in calcium-regulatory proteins may also directly
      contribute to the development of extraosseus calcifications. alpha(2)-Heremans
      Schmid glycoprotein and matrix Gla protein are important inhibitors of
      calcification in vivo and there is novel evidence available that a deficiency in
      such proteins is involved in the pathogenesis of cardiovascular calcifications in
      dialysis patients.

PMID- 12207097
TI  - Incidence of infectious morbidity and mortality in dialysis patients.
AB  - Infections remain among the major causes of disease, hospitalization and death in
      uremic patients, especially in those treated by dialysis. Several
      pathophysiologic factors enhance this infectious risk: (1) breakdown of
      protective barriers; (2) affinity of bacteria for foreign materials; (3)
      bioincompatibility; (4) uremic toxin retention; (5) deficiency and resistance to
      vitamin D; (6) carriership of germs, and (7) malnutrition. Twenty to 30% of
      dialysis patients develop infection, and 20-30% of these die from their
      infection. Sepsis is significantly more frequent, and mortality secondary to
      sepsis is 50 times higher than in the normal population. Bacteremia (prevalence 1
      episode/100 patient-months) is mainly caused by Gram-positive species, especially
      in vascular access-related infection and infection of unknown origin. Among these
      Gram-positive germs, staphylococci play a predominant role. The most frequent and
      most morbid viral infections are associated with hepatitis. Whereas the incidence
      of hepatitis B decreases, hepatitis C has become the major variant. The incidence
      of tuberculosis has increased up to 15 times, and in the Western world it mainly
      affects patients who immigrated from endemic areas. Fungal infections are also
      frequent, especially in the setting of peritoneal dialysis. In conclusion,
      infections remain a frequent and morbid problem in dialysis patients. Preventive
      measures should be applied more vigorously.

PMID- 12207098
TI  - Immune system dysregulation in uremia: role of oxidative stress.
AB  - Immune system dysregulation in end-stage renal disease patients is a
      multifactorial process combining profound immunodeficiency with a state of
      cellular activation. While at the origin of the deficiency uremic toxins are
      thought to play a prominent role, the dialysis procedure is the main factor for
      the genesis of a recurrent cellular activation process leading to a chronic
      inflammation state dominated by oxidative stress and its related severe
      complications, e.g. beta(2)-microglobulin amyloid arthropathy and accelerated
      atherosclerosis. The recent identification of advanced oxidation protein products
      (AOPPs) in the plasma of uremic patients and the following demonstration that
      AOPPs act as both potential uremic toxins and proinflammatory mediators, have
      opened novel areas of research on these novel molecular bases of oxidative stress
      and on therapeutic strategies aimed at reducing its most deleterious effects in
      hemodialysis patients.

PMID- 12207099
TI  - Humoral immune responses in uremia and the role of IL-10.
AB  - Chronic renal failure severely influences the immune functions of the host.
      Recent work has shown that uremic intoxication as well as its treatment alters
      distinct aspects of immunity and that the organism has certain mechanisms to
      compensate, at least in part, for these influences. Failure of the humoral branch
      of immune function becomes apparent when vaccinations are applied to the dialysis
      patient. Severely impaired vaccine responses are common, particularly against
      hepatitis B, tetanus, or influenza. In contrast, patients with chronic renal
      failure may develop adequate humoral responses against vaccines such as
      pneumococcus. The degree of impairment of humoral responses is related to the
      antigen's dependence on T-helper lymphocyte activation, which is high for
      hepatitis or influenza, and low for large polysaccharide antigens. T-helper cell
      activation on the other hand is greatly influenced by inflammatory processes,
      e.g. the secretion of cytokines such as interleukin (IL-)-1 or IL-6. These
      inflammatory processes are induced by uremic toxins and contacts between blood
      and extracorporeal surfaces of the dialysis equipment. They are subject to the
      body's compensatory mechanisms for inflammation, which are mainly based on the
      anti- inflammatory cytokine IL-10. Genetically determined differences in the
      secretion capacity for this compensatory cytokine strongly influence humoral
      immunity in the patient with chronic renal failure and thus allow the definition
      of a high-risk group for infection and vaccine nonresponse.

PMID- 12207100
TI  - Peritoneal membrane failure in peritoneal dialysis patients.
AB  - A review is given of the conditions associated with peritoneal membrane failure,
      and the possible causes. Ultrafiltration failure is the most important
      manifestation. It is mostly associated with high transport rates of low molecular
      weight solutes suggesting the presence of a large vascular surface area.
      Enlargement of the peritoneal surface area can be functional (effective surface
      area: more perfused microvessels) or anatomic (more microvessels). The former is
      likely to be present in some patients in the beginning of peritoneal dialysis,
      and also during peritonitis. The latter can develop in long-term peritoneal
      dialysis.

PMID- 12207101
TI  - Advanced oxidation protein products, parathyroid hormone and vascular
      calcification in uremia.
AB  - Vascular calcification is a frequent complication of uremic patients. In addition
      to classical risk factors such as age, male gender, smoking, inflammation,
      hypertension, dyslipidemia, and diabetes, which also exist in the general
      population, patients with chronic renal failure have other risk factors such as
      oxidative stress, inflammation, hyperparathyroidism, hypoparathyroidism,
      hypercalcemia, hyperphosphatemia, and overtreatment with calcium and vitamin D.
      These latter risk factors may even have a better predictive value than classical
      risk factors for coronary heart disease in uremic patients.

PMID- 12207103
TI  - Assay sensitivity, failed clinical trials, and the conduct of science.

PMID- 12207104
TI  - Atypical antipsychotic drug use and diabetes.
AB  - Recently, there has been increased concern about the occurrence of diabetes
      associated with the use of atypical antipsychotic (AAP) drugs. The relationship
      between diabetes, schizophrenia, and antipsychotic drugs is complex and
      intriguing, as untreated patients with schizophrenia are known to suffer from
      diabetes more often than the general population. Thirty individual case reports
      of clozapine-, 26 cases of olanzapine- and a few others of seroquel- and
      risperidone-associated diabetes mellitus, hyperglycemia and diabetic ketoacidosis
      were found by a Medline search. The case reports do not provide the incidence of
      diabetes in patients treated with AAP drugs, but they suggest that AAP drugs may
      cause hyperglycemia. Further research is needed to identify the cause of the
      susceptibility of the schizophrenic population, and to elucidate the mechanisms
      by which the antipsychotic drugs either cause diabetes or precipitate its onset.
      Which antipsychotic drugs have a higher and which have a lower potential to
      induce diabetes is not conclusively answered at present. However, the findings
      that 50% of the patients completely improve upon drug discontinuation, and that
      hyperglycemia promptly recurs upon reinstitution of the incriminated drug
      indicate that this side effect is reversible and is drug related. African
      Americans are particularly susceptible to AAP drug-induced diabetes. Until the
      new research data become available, AAP drug treatment of schizophrenic patients
      aims at prevention, institution of vigilant screening procedures, and management
      of hyperglycemia.

PMID- 12207105
TI  - Obsessive-compulsive symptom dimensions as predictors of compliance with and
      response to behaviour therapy: results from a controlled trial.
AB  - BACKGROUND: Recent factor-analytic studies in obsessive-compulsive disorder (OCD)
      identified consistent symptom dimensions. Support for the validity of these
      dimensions comes from studies of psychiatric comorbidity, functional brain
      imaging, genetic transmission, and treatment response to medications. This study
      examined whether previously identified OCD symptom dimensions are associated with
      treatment compliance and response to behaviour therapy (BT) for OCD. METHODS: One
      hundred and fifty-three OCD outpatients who participated in a multi-centre
      randomised controlled trial of computer- versus clinician-guided BT for OCD were
      included in the study. Logistic and multiple regression models tested for
      significant predictors of compliance with and response to BT and relaxation.
      RESULTS: The patients studied were phenomenologically comparable (including the
      presence of 'pure' obsessions and mental rituals) to those in previous serotonin
      reuptake inhibitor (SRI) trials and those in clinical epidemiology studies. High
      scorers on the 'hoarding' dimension were more likely to drop out prematurely from
      the study and tended to improve less. For those completing treatment, the
      strongest predictor of outcome was pre-treatment severity. Initial depression
      scores were unrelated to outcome. After controlling for symptom severity, higher
      scores on the 'sexual/religious obsessions' factor predicted poorer outcome with
      BT, especially when computer-guided. CONCLUSIONS: BT is especially indicated for
      OCD patients with aggressive/checking, contamination/cleaning and
      symmetry/ordering symptoms. Previous accounts of unsuccessful BT in patients with
      hoarding symptoms may be due in part to their propensity to drop out earlier from
      treatment. Patients with sexual/religious obsessions, but not those with mental
      rituals, might respond less well to traditional BT techniques. Existing
      treatments need to be refined and/or new treatments developed to improve these
      patients' adherence and response to treatment.

PMID- 12207106
TI  - The relevance of psychiatric and somatic comorbidity in depressed chronic
      benzodiazepine users.
AB  - BACKGROUND: Comorbid conditions may add to the burden of depressed patients and
      hamper their treatment. We therefore investigated the impact of anxiety disorders
      and somatic comorbidity in a group of depressed chronic benzodiazepine users on
      disease status, treatment, benzodiazepine history and discontinuation outcome.
      METHODS: At screening for a discontinuation programme, full psychiatric status
      was determined using the MINI-interview and psychopathology was assessed using
      several rating scales. Relevant medical history, including surgeries, was
      recorded as well. RESULTS: Patients with comorbid anxiety disorders were 8 years
      younger (p < 0.001), more anxious (p = 0.004) and reported more benzodiazepine
      withdrawal symptoms (p = 0.011) than depressed patients without comorbid anxiety
      disorders. They also had been using more long-acting benzodiazepines (p = 0.003),
      in higher dosages (p = 0.019). However, this did not result in more difficulty in
      tapering off benzodiazepines, either at post-test, or at follow-up 2.3 years
      later. Somatic comorbidity was not associated with the level of psychopathology
      and not related to the outcome of the discontinuation programme. CONCLUSIONS:
      Comorbid anxiety disorders are associated with a more severe disease status in
      depressed chronic benzodiazepine users, but have no influence on the
      benzodiazepine discontinuation. Somatic comorbidity has no impact on the severity
      of the psychopathology, or on benzodiazepine discontinuation.

PMID- 12207107
TI  - Treatment-resistant depression and Axis II comorbidity.
AB  - BACKGROUND: Researchers of unipolar depression have speculated that personality
      disturbance is a contributing factor in the development of treatment resistance.
      The purpose of this study was to compare the prevalence of Axis II disorders
      between a sample of rigorously defined, treatment-resistant depressed outpatients
      and a sample of depressed outpatients not having experienced treatment
      resistance. METHODS: 53 patients with treatment-resistant depression (TRD) and
      105 patients with non-treatment-resistant depression (non-TRD) were recruited
      through respective outpatient clinical trials at the Massachusetts General
      Hospital's Depression Clinical and Research Program. Diagnosis of Major
      Depressive Disorder was made using the Structured Clinical Interview for the DSM
      III-R, personality disorders were assessed using the Structured Clinical
      Interview for DSM-III-R Personality Disorders, and antidepressant treatment
      resistance was defined using the McLean Hospital Antidepressant Treatment Record.
      Participants from both studies were matched for baseline HAM-D-17 total score and
      gender. Multiple chi-square analysis was used to compare frequencies of Axis II
      disorders between TRD and non-TRD patients as well as to compare categorical
      baseline demographic variables. Unpaired t tests were used to compare baseline
      demographic and clinical variables measured in a continuous manner. RESULTS: Non
      TRD patients had a higher rate of obsessive-compulsive personality disorder than
      TRD patients, but this difference was not statistically significant after
      adjusting for multiple comparisons. No other differences were found to be
      statistically significant. Range of Axis II comorbidity was 0.0-30.2% for TRD
      patients and 2.9-37.1% for non-TRD patients. CONCLUSIONS: In this sample,
      treatment resistance in a current major depressive episode was not associated
      with an increased rate of Axis II disorders. Strengths of this study include the
      use of structured interview instruments to assess Axis I and II conditions, and
      having the two study groups matched for gender and baseline severity of
      depression. Limitations of this study include a modest sample size and reliance
      on DSM personality constructs.

PMID- 12207108
TI  - Subjective quality of life: its relationship with clinician-rated and patient
      rated psychopathology. The South-Verona Outcome Project 6.
AB  - BACKGROUND: The study compared clinician-rated and patient-rated psychopathology
      and analysed their relationship with subjective quality of life (QoL) in a sample
      of patients with a wide range of psychiatric conditions attending a community
      based mental health service. METHODS: In the context of the South-Verona Outcome
      Project (SVOP), 139 patients were assessed for both clinician-rated and self
      rated psychopathology (by using respectively the Brief Psychiatric Rating Scale
      and the revised version of the Symptom Checklist 90), and asked to report on
      their subjective quality of life (by using the Lancashire Quality of Life
      Profile). In order to explore the associations between psychopathology and
      subjective QoL bivariate and multivariate analyses were performed. RESULTS: BPRS
      and SCL-90-R were poorly correlated, both in their total scores and in their
      various dimension scores. BPRS showed only a modest negative correlation with
      LQL, which, in contrast, was highly negatively correlated with SCL-90-R.
      Regression analyses showed that patient-rated psychopathology was the strongest
      predictor of subjective quality of life, with self-rated depressive symptoms and
      self-reported paranoid ideation having the highest predictive power. CONCLUSIONS:
      Self-reported psychological distress is more important than clinician-rated
      symptom severity in predicting subjective QoL. In order to improve QoL,
      psychiatric treatment should focus not only on simple reduction of symptoms but
      also on patients' subjective psychological distress.

PMID- 12207109
TI  - Psychiatric and psychosocial outcome of orthotopic liver transplantation.
AB  - BACKGROUND: The study aimed to explore the prevalence of psychiatric disorders
      among orthotopic liver transplantation (OLT) recipients, and to investigate how
      psychiatric morbidity was linked to health-related quality of life (HRQOL).
      METHODS: We recruited 75 patients who had undergone OLT a median of 3.8 years
      previously (range = 5-129 months). Psychiatric morbidity was assessed using the
      Structural Clinical Interview for the DSM-III-R. Psychometric observer-rating and
      self-rating scales were administered to evaluate cognitive functioning (SKT),
      depressive symptomatology (HAMD(17)), posttraumatic stress symptoms (PTSS-10),
      social support (SSS), and HRQOL (SF-36 Health Status Questionnaire). Treatment
      characteristics were obtained from medical records. RESULTS: 22.7% (n = 17) of
      our sample had a current or probable psychiatric diagnosis according to DSM-III
      R: 2.7% full posttraumatic stress disorder (PTSD) (n = 2), 2.7% major depressive
      disorder (MDD) comorbid to full PTSD (n = 2), 1.3% MDD comorbid to partial PTSD
      (n = 1), and 16% partial PTSD (n = 12). Patients with PTSD symptoms demonstrated
      lower cognitive performance, higher severity of depressive symptoms and more
      unfavorable perception of social support. OLT-related PTSD symptomatology was
      associated with maximal decrements in HRQOL. The duration of intensive care
      treatment, the number of medical complications, and the occurrence of acute
      rejection were positively correlated with the risk of PTSD symptoms subsequent to
      OLT. CONCLUSION: OLT-related PTSD symptomatology impairing HRQOL is a
      complication for a subgroup of OLT recipients. Health-care providers should be
      aware of the possible presence of PTSD in OLT survivors.

PMID- 12207110
TI  - Elevated blood levels of dehydroepiandrosterone sulphate vary with symptom load
      in posttraumatic stress disorder: findings from a longitudinal study of refugees
      in Sweden.
AB  - BACKGROUND: The present study is part of a longitudinal study of recently
      resettled refugees with the aim of learning which factors in their daily life
      influence health as measured by self-report and stress-responsive hormones.
      METHODS: In a group of recently resettled refugees with a high incidence of
      posttraumatic stress disorder (PTSD), diagnosed by structured interview, self
      rated symptoms of PTSD were followed three times over a period of 9 months after
      inclusion in the study. Eighty-six individuals were included in the study and 58
      subjects (67.4%) completed it. Blood samples were drawn at each examination for
      assessment of hormone levels. RESULTS: After adjustment for age,
      dehydroepiandrosterone sulphate (DHEA-s) was observed to be higher in non
      depressed PTSD cases than in non-PTSD without depression. There was an
      interaction between PTSD and depression regarding DHEA-s levels. DHEA-s
      correlated significantly with changes in self-rated symptoms of PTSD at last
      follow-up; the greater the increase in PTSD symptoms, the greater the increase in
      plasma DHEA-s. The variation of DHEA-s levels in relation to changes in self
      rated health in non-PTSD showed the opposite pattern, although not reaching
      significance. CONCLUSIONS: The finding of changes in DHEA-s should encourage
      further studies of the role of altered steroid metabolism in PTSD.

PMID- 12207111
TI  - In vitro effect of fluticasone propionate on interleukin 8 production by
      monocytes obtained from patients affected by moderate-severe allergic asthma.
AB  - BACKGROUND: Interleukin-8 (IL-8), a potent chemotactic and activating factor for
      neutrophils and eosinophils, may be a crucial factor in severe asthma. The aim of
      this study was to evaluate the effect of fluticasone propionate (FP), a
      corticosteroid with potent anti-inflammatory activity, on the in vitro release of
      IL-8 by monocytes obtained from asthmatic patients. METHODS: Monocytes from 15
      non-atopic healthy donors and from 15 patients affected by moderate-severe
      allergic asthma were isolated and incubated (37 degrees C, 5% CO(2)) for 24 h
      with varying combinations of lipopolysaccharide (LPS) from Escherichia coli (1
      microg/ml) and FP (100 nmol/l). IL-8 concentration in the culture supernatant was
      measured by an immuno-enzymatic method (ELISA). RESULTS: A highly significant
      inverse correlation between FEV1 (forced expiratory volume) values before
      withdrawal and in vitro IL-8 production by unstimulated monocytes from asthmatic
      patients was observed (Rho = -0.787; p = 0.0032). IL-8 production by either LPS
      stimulated or unstimulated monocytes from asthmatic subjects was statistically
      increased compared to monocytes from healthy donors (p < 0.05). FP addition
      reduced IL-8 production by monocytes from asthmatic patients and also from
      healthy donors (p < 0.05). CONCLUSIONS: The partial IL-8 inhibition by FP could
      be closely related to the anti-inflammatory activity of this corticosteroid.
      Based on these results, we propose that the clinical improvement of asthma,
      observed following FP administration, may depend, at least in part, on the
      ability of this drug to modulate cytokine production by monocytes.

PMID- 12207112
TI  - Smooth muscle, neurons and interstitial cells of guinea pig ileum: are there
      tachykinin neurokinin 1 receptor subtypes?
AB  - Binding and autoradiographic studies were carried out in guinea pig ileum to
      examine neurokinin (NK) 1 receptor location and subtypes using the NK-1-selective
      radioligand [(125)I]Bolton-Hunter[Sar(9),Met(O(2))(11)]SP. Two membrane
      preparations were made: (1) longitudinal muscle containing the myenteric plexus
      and (2) circular muscle containing the interstitial cells of Cajal. In saturation
      binding studies, the K(D) was estimated as 1.3 and 1.0 nmol/l in each
      preparation, respectively. In competition binding, the rank order of potency was
      similar in both membrane preparations: SR140333 approximately CP99994 > or =
      [Sar(9),Met(O(2))(11)]SP approximately physalaemin approximately CP96345 (pIC(50)
      9.5-8.7) >> neuropeptide gamma > or = septide (pIC(50) 7.8-7.4). Similarly,
      scyliorhinin I displayed equal affinity in both preparations, although binding
      was at two sites, of high affinity (pIC(50) 9.1, 30%) and low affinity (pIC(50)
      7.2-6.6, 70%). The only competitor to bind differently in the two muscle
      preparations was scyliorhinin II, which bound to one site with low potency in the
      circular muscle (pIC(50) 6.9) but to high-affinity (pIC(50) 9.0, 17%) and low
      affinity (pIC(50) 6.7, 83%) sites in the longitudinal muscle. In autoradiographic
      studies, dense specific binding was associated with the myenteric plexus and the
      inner circular muscle containing the interstitial cells of Cajal, with minimal
      specific binding to longitudinal and circular smooth muscle. These results
      suggest that the NK-1 receptor on the interstitial cells and the myenteric plexus
      is similar. The apparently low numbers of binding sites on intestinal smooth
      muscle may be due to a low expression of the NK-1 receptor. Alternatively, the
      radioligand may not recognize the guinea pig ileum muscle NK-1 receptors due to
      possible minor differences in their sequence or glycosylation.

PMID- 12207113
TI  - Gastric damage induced by subchronic administration of preferential
      cyclooxygenase-1 and cyclooxygenase-2 inhibitors in rats.
AB  - Nonsteroidal anti-inflammatory drugs (NSAIDs) are well known to induce
      gastrointestinal damage including bleeding, ulceration and perforation in humans
      and animals. The aim of this study was to compare the effects of two oxicams,
      preferential cyclooxygenase (COX)-1 or COX-2 inhibitors, on both gastric mucosa
      and some biological parameters (hematological, hepatic and renal) after
      subchronic administration (14 and 28 days) in rats. Neutrophil infiltration was
      also assessed. Equipotent doses of meloxicam (3.75 and 7.5 mg/kg) and piroxicam
      (5 and 10 mg/kg) were administered. Both drugs dose-dependently caused multiple
      gastric erosions and hemorrhage in rats after 14 and 28 days of administration.
      Treatment with meloxicam led to a higher gastric damage than with piroxicam on
      day 14 although these results were not significant. The levels of myeloperoxidase
      activity (as an index of neutrophil infiltration) were not changed compared with
      control after drug treatment. All the hematological parameters obtained after
      drugs administration for 14 and 28 days were in the range of normal values, and a
      significant increase in platelet levels could be observed in the group treated
      with 5 mg/kg of piroxicam for 14 days. Aspartate aminotransferase (AST or GOT)
      increased significantly after 14 days, but after 28 days the values returned to
      normality. Creatinine and urea did not undergo significant changes except for the
      piroxicam 14-day 5 mg/kg group, in which uremia increased significantly over
      normal values. In conclusion, our results show that meloxicam, a preferential COX
      2 inhibitor, causes rates of gastric lesion comparable to those seen with
      traditional NSAIDs, without inducing important changes in biological parameters.

PMID- 12207114
TI  - Intrathecal bradykinin administration: opposite effects on nociceptive
      transmission.
AB  - Injected intrathecally, bradykinin (BK) produced either hyperalgesia (0.15
      microg) or antinociception (6.0 microg) in rats when thermal noxious stimuli were
      used. Similarly, des-Arg(9)-BK at the lower dose (0.15 microg) decreased, whereas
      at the higher dose (6.0 microg) it increased the threshold to thermal noxious
      stimuli; however, these effects were less pronounced than those of BK. The
      antinociception induced by BK was abolished by HOE 140, a B(2) receptor
      antagonist, injected intrathecally at a dose of 1.3 ng and was markedly
      attenuated by des-Arg(10)-HOE 140, a B(1) receptor antagonist (1.15 ng i.t.). The
      results obtained in this study showed that--depending on the dose used--BK and
      des-Arg(9)-BK could produce pro- as well as antinociceptive actions. Both B(2)
      and B(1) receptors are involved in the action of intrathecally applied BK.

PMID- 12207115
TI  - Effects of SK-1080 on intimal thickening and impaired vascular relaxation after
      balloon injury in rats.
AB  - We investigated the effects of SK-1080, a novel angiotensin AT(1) receptor
      antagonist, on neointimal proliferation in the rat carotid artery after balloon
      injury, together with its effects on the impaired endothelium-dependent vascular
      relaxation. SK-1080 (0.3 and 1.0 mg/kg/day) was orally administered in balloon
      injured rats for 21 days (from 6 days before to 14 days after balloon injury). SK
      1080 (1 mg/kg) exerted significant effects on three important parameters
      associated with the intimal thickening induced by balloon injury (50.0% reduction
      in neointimal area, 42.7% reduction in stenosis ratio and 69.1% increase in
      lumen/total area ratio). Acetylcholine-induced relaxation was significantly
      reduced in the balloon-injured carotid arteries (64.0 +/- 9.1%), and this
      impairment of acetylcholine-induced relaxation was significantly restored by SK
      1080 (maximal relaxation: 87.1 +/- 6.5 and 88.6 +/- 1.9% at 0.3 and 1.0 mg/kg,
      respectively, p < 0.05). However, the endothelial-independent, sodium
      nitroprusside-induced relaxation was clearly demonstrated and did not differ in
      carotid arteries from all treatment groups. Furthermore, acetylcholine-induced
      relaxation was completely inhibited by L-NAME but not by indomethacin. SK-1080
      caused a slight hypotension 1 day before balloon injury (8.7%), which gradually
      returned to the baseline 6 and 13 days after balloon injury. These results
      suggest that SK-1080 may have therapeutic potential for the treatment of vascular
      diseases such as restenosis and atherosclerosis.

PMID- 12207116
TI  - Paradoxical pharmacological effects of deoxy-tetrahydrocannabinol analogs lacking
      high CB1 receptor affinity.
AB  - The present study investigated the role of peripheral cannabinoid (CB(2))
      receptors in producing hypomobility, antinociception and hypothermia in mice.
      Results revealed that the CB(2)-selective antagonist, SR144528, did not block
      cannabimimetic effects of a potent delta(8)-tetrahydrocannabinol (THC) analog in
      mice. While most of a series of CB(2)-selective 1-deoxy-THC analogs were active
      in vivo only if they also had good affinity for CB(1) receptors, four of these
      analogs showed in vivo activity even though their affinities for CB(1) receptors
      were poor. Further, this activity was blocked by the CB(1) antagonist SR141716A,
      but not by SR144528. One of the deoxy analogs also stimulated [(35)S]GTPgammaS
      binding, an effect that was blocked by SR141716A. These results provide further
      evidence that these cannabimimetic effects are not mediated through action at
      CB(2) receptors. In addition, some of these analogs may be very low efficacy
      agonists at CB(1) receptors that act as full agonists in vivo, but lack the
      ability to displace high affinity and high efficacy binding ligands in vitro.

PMID- 12207117
TI  - Effect of bremazocine, a kappa-opioid receptor agonist, on inositol phosphate
      formation in isolated iris-ciliary bodies.
AB  - The goal of the current study was to examine the effect of the kappa-opioid
      agonist, bremazocine (BRE), on inositol phosphate (IP) formation in the rabbit
      iris-ciliary body (ICB). Concentrations of BRE (10(-7) to 10(-5) M) augmented
      levels of IP. Incubation of ICBs with BRE (10(-6) M) produced a time-dependent
      increase in IP levels that peaked at 60 s and declined to basal levels by 5 min.
      The increase in IP levels produced by BRE (10(-6) M) was inhibited by the kappa
      opioid receptor antagonist, nor-binaltorphimine (nor-BNI, 10(-7) to 10(-5) M) and
      by activation of PKC with PDBu (10(-7) M). These results demonstrate that kappa
      opioid receptor activation by BRE in the rabbit ICB is linked to IP production.
      Thus, opioid agonist-induced increases in IP activity could play a role in BRE
      induced increases in atrial natriuretic peptide release and alterations in
      aqueous humor dynamics.

PMID- 12207118
TI  - Effect of SMP-500, a novel acyl-CoA:cholesterol acyltransferase inhibitor, on
      serum cholesterol level and LDL cholesterol clearance in hamsters with induced
      hyperlipidemia.
AB  - The effect of SMP-500, a novel acyl-CoA:cholesterol acyltransferase (ACAT)
      inhibitor, on serum cholesterol levels was investigated in hyperlipidemic
      hamsters whose condition had been preestablished by diet. SMP-500 reduced the
      total serum cholesterol level in a dose-dependent manner. SMP-500 also reduced
      the hepatic free cholesterol content and markedly reduced the esterified
      cholesterol content compared with the control group. Interestingly, SMP-500 at a
      dose of 30 mg/kg increased LDL clearance in vivo. As SMP-500 at this dose
      potently lowered the total serum cholesterol level, the increased LDL clearance
      was identified as another mechanism for the cholesterol-lowering effect of SMP
      500. However, unlike HMG CoA reductase inhibitors, SMP-500 did not affect
      cholesterol biosynthesis in HepG2 cells. Therefore the etiology of the increased
      LDL clearance is not yet clear, but the reduced hepatic free cholesterol may play
      an important role in this process. These results suggest that the cholesterol
      lowering effect of SMP-500 is due, not only to the inhibition of ACAT, but also
      to the increase in cholesterol clearance from the blood. This finding supports
      the therapeutic potential of SMP-500 for the treatment of human
      hypercholesterolemia.

PMID- 12207119
TI  - The subretinal implant: can microphotodiode arrays replace degenerated retinal
      photoreceptors to restore vision?

PMID- 12207120
TI  - T cells in autoimmune disorders.

PMID- 12207121
TI  - Management of presbyopia with soft contact lenses.

PMID- 12207122
TI  - Colour Doppler assessment of blood flow in eyes with central retinal vein
      occlusion.
AB  - PURPOSE: To assess the blood flow changes in eyes with central retinal vein
      occlusion (CRVO) and compare these values with values of fellow eyes and eyes of
      normal subjects. METHODS: 25 eyes of 25 consecutive newly diagnosed patients with
      CRVO comprised the study group. Their fellow eyes and those of 25 healthy
      subjects were the control group. All patients underwent a complete
      ophthalmological examination. Eyes with CRVO were classified into two groups as
      non-ischaemic and ischaemic by fundus fluorescein angiography. Colour Doppler
      imaging was performed with a Toshiba Sonolayer SSH-140A and 7.5-MHz linear array
      probe. Maximum systolic velocity (V(max)), end-diastolic velocity (V(min)) and
      resistive index (R(i)) values were noted for each of the central retinal artery
      (CRA), central retinal vein (CRV) and ophthalmic artery (OA). These parameters
      were compared with those of the fellow eyes and both eyes of the control group.
      RESULTS: Mean ages were 63.55 and 61.45 years in the CRVO and control groups,
      respectively. Age and sex distributions were statistically identical in both
      groups. When we compared the eyes with CRVO to the control group, no
      statistically significant difference existed between the two groups with regard
      to the V(min) and R(i )values of the CRA and CRV. However, V(max ) values of the
      CRA and CRV were significantly lower in CRVO eyes when compared to the control
      group. The CRVO group and control group had similar V(max), V(min ) and R(i)
      values for the OA. Only the V(max) was significantly lower in the CRV in eyes
      with CRVO when compared to the unaffected fellow eyes. No statistically
      significant difference could be detected between any of the parameters of CRA,
      CRV and OA of the ischaemic and non-ischaemic CRVO groups. CONCLUSIONS: More data
      on broader series need to be obtained in order to decide on the practical use of
      colour Doppler imaging in the differentiation of ischaemic eyes from non
      ischaemic eyes in CRVO.

PMID- 12207123
TI  - Deep sclerectomy with collagen implant: initial experience.
AB  - OBJECTIVE: To evaluate complications of deep sclerectomy with collagen implant
      (DSCI), a recently introduced nonpenetrating glaucoma-filtering surgical
      technique. PATIENTS AND METHODS: 30 eyes of 23 patients with open-angle glaucoma
      were included in this prospective, noncomparative, interventional case series. In
      all eyes, preoperative intraocular pressure (IOP) was lowered inadequately by
      topical antiglaucomatous medications. After undergoing DSCI, the patients were
      followed prospectively. If necessary, the procedure was combined with cataract
      surgery or mitomycin C application. RESULTS: In 27 (90%) of 30 eyes, DSCI could
      be performed. In 3 (10%) of 30 eyes, DSCI had to be transformed intraoperatively
      into a trabeculectomy because of a large trabecular penetration.
      Microperforations without further consequences occurred in 2 (7%) of 30 eyes. The
      mean follow-up was 6.6 +/- 3.8 months. IOP dropped from 26.0 +/- 6.7 to 13.6 +/-
      4.7 mm Hg (p < 0.05). Medical glaucomatous treatment was reduced from 2.3 +/- 3.8
      to 0.3 +/- 0.6 (p < 0.05). In cases without cataract, visual acuity decreased
      from 0.7 +/- 0.3 to 0.66 +/- 0.4 at the last visit (p > 0.1). Postoperative
      complications included Seidel (1/27, 4%), encapsulated bleb (4/27, 15%),
      astigmatism (1/27, 4%), iris capture (2/27, 7%), microhyphema (3/27, 11%) and
      peripheral anterior synechiae (4/27, 15%). Fifteen (56%) of the 27 eyes needed
      the following postoperative procedures: laser goniopuncture (8/27, 30%), needling
      of the filtering bleb (4/27, 15%), surgical revision in the operating theater
      (3/27, 11%). All 3 eyes where trabeculectomy was performed instead of DSCI had a
      favorable course. CONCLUSIONS: During the evaluation period, complications
      occurred in about half of the cases. None of the complications was severe or
      irreversible. Target pressure and a reduction in drug treatment could be achieved
      in all of the patients.

PMID- 12207124
TI  - Axial length measurements after cataract surgery in adults.
AB  - The purpose of the study was to check the difference in eye axial length before
      and after cataract surgery and to find out the possible correlation with
      refraction changes. The axial length was measured by ultrasound before and after
      cataract extraction with intraocular lens implantation. Keratometry measurements
      were also performed. The study comprised 32 eyes. The mean difference in axial
      length was 0.53 mm. The mean difference in keratometry was 0.37 D. There was no
      correlation between these values. CONCLUSION: The changes in axial length are not
      due to corneal curve changes. Perhaps in pseudophakic eyes different ultrasound
      velocity should be used.

PMID- 12207125
TI  - The role of the vitreous in retinal detachment surgery with external buckling.
AB  - PURPOSE: To prove the role of the vitreous in retinal detachment surgery with
      scleral buckling procedures, we retrospectively investigated the charts of
      patients who were operated on for retinal detachment by scleral buckling between
      January 1995 and June 1997. METHODS: Out of a total of 718 cases, 41 retinal
      detachments occurred in previously vitrectomized eyes. The buckling procedure
      consisted of silicone sponge explants in 513 cases (254 radial, 259
      circumferential) and of encircling elements in 202 cases. Three eyes received a
      temporary balloon. The minimal follow-up was 3 months. RESULTS: After primary
      surgery in the 677 nonvitrectomized eyes, the retina was attached in 482 eyes
      (71.2%), after reoperation in 627 eyes (92.6%). With up to 3 reoperations
      (including vitrectomy with gas or silicone oil tamponade in 79 eyes), the final
      success rate was 98.7%. The corresponding reattachment rates in the 41
      vitrectomized eyes were 82.9% after primary surgery and 97.6% after reoperation.
      Repeated surgery in 6 eyes consisted of successful internal tamponade by silicone
      oil. The reattachment rates after primary buckle procedure are of most interest
      to the role of the vitreous: the highest success rate (82.9%) was achieved in the
      vitrectomized eyes versus 71.2% in the nonvitrectomized eyes. The difference is
      statistically not significant. CONCLUSIONS: We therefore conclude that the
      absence of the vitreous has no adverse effect on the results of buckling
      procedures for retinal detachment. The choice of the surgical technique in
      treating retinal detachments in vitrectomized eyes should only determined by
      retinal findings such as the number and extent of breaks or the presence and
      stage of proliferative vitreoretinopathy.

PMID- 12207126
TI  - Consecutive exotropia following strabismus surgery.
AB  - We investigated the clinical factors affecting the development of consecutive
      exotropia following esotropia surgery. The development period of consecutive
      exotropia, amblyopia and limitation of adduction were evaluated in 89 patients
      with primary esotropia that changed to consecutive exotropia after surgery. In
      the presence of deep amblyopia, consecutive exotropia developed earlier. When two
      horizontal muscles were operated, limitation of adduction was more frequent in
      symmetrical rather than asymmetrical surgical procedure. Since consecutive
      exotropia may develop many years after esotropia surgery, a long-term follow-up
      period in patients without consecutive exotropia in the early postoperative
      period is advised.

PMID- 12207127
TI  - Outcome of penetrating keratoplasty in rheumatoid arthritis.
AB  - BACKGROUND: Keratolysis in rheumatoid arthritis is a well-known disorder that may
      rapidly destroy the entire corneal stroma, resulting in descemetocele formation
      and eventually corneal perforation. The purpose of this study was to determine
      the anatomical and functional results of therapeutic penetrating keratoplasty
      (PK) in these patients. PATIENTS AND METHODS: We reviewed the charts of patients
      having undergone PK over a 5-year period and evaluated the outcome. In 16 eyes of
      15 patients, PKs were performed (graft diameter 3.0-11.0 mm) because of corneal
      melting with perforation or descemetocele formation. In 9 eyes, we used topical
      cyclosporine A (2%) as an adjunct therapy after transplantation in addition to
      systemic immunosuppressive agents. RESULTS: Following a mean follow-up time of 17
      months, anatomical success could be achieved in all eyes; none of the eyes
      underwent enucleation or evisceration. Postoperative complications following the
      first PK were epithelial keratopathy in 8 eyes (50%), corneal ulceration in 5
      eyes (31%), fistulation in 4 eyes (25%), suture loosing in 4 eyes (25%) and graft
      rejection in 2 eyes (13%). Additionally 5 regrafts were required because of
      recurrence of corneal melting or persistent deep stromal defects. Comparison of
      complications of the patients receiving topical cyclosporine A to the control
      group showed a statistically significant lower incidence of epithelial
      keratopathy (p < 0.025) and ulcer recurrence in the cyclosporine A group during
      the first 3 months postoperatively (p < 0.05). The final best corrected visual
      acuity was 20/40 in 4 eyes but was limited to 20/200 or less in 7 eyes.
      CONCLUSION: Whereas PK can be successful to restore the anatomical integrity of
      severely altered eyes, the high prevalence of complications limits the indication
      for PK as a last stage procedure when other methods of management have failed.
      The use of topical cyclosporine A as adjunct therapy needs further evaluation.

PMID- 12207129
TI  - Intravitreal penetration of cefepime after systemic administration to humans.
AB  - PURPOSE: To investigate the penetration of cefepime (a fourth-generation
      cephalosporin) into the vitreous after single-dose intravenous administration to
      human subjects. METHODS: Thirty phakic patients about to undergo vitreous surgery
      received 1 g (group 1, 15 patients) or 2 g cefepime (group 2, 15 patients) in a
      single intravenous injection before surgery. The indications for vitreous surgery
      were retinal detachment with proliferative vitreoretinopathy (24 patients),
      retinal detachment associated with giant retinal tear (4 patients), macular hole
      (1 patient) and intraocular foreign body (1 patient). Samples of vitreous and
      serum were obtained at 0.5, 1, 2, 4 and 12 h after injection. Three patients were
      used for each sampling time and for 1 g and 2 g of cefepime. Samples were assayed
      for cefepime concentrations with high-performance liquid chromatography (HPLC).
      RESULTS: All the patients had detectable cefepime in their vitreous and serum
      measurable by HPLC. The level of cefepime in the vitreous peaked at 2 h and
      reached a minimum at 12 h after intravenous injection in both groups. A mean peak
      vitreous level of cefepime was 1.91 +/- 0.13 microg/ml in group 1 and 2.86 +/-
      0.37 microg/ml in group 2. The level of cefepime in the vitreous at 12 h after
      injection was 0.89 +/- 0.14 microg/ml in group 1 and 0.97 +/- 0.30 microg/ml in
      group 2. CONCLUSION: The vitreous level of cefepime after intravenous injection
      was below the minimum inhibitory concentration (MIC(90)) against Staphylococcus
      aureus, Staphylococcus epidermidis and Pseudomonas aeruginosa, but was over the
      MIC(90) against Proteus mirabilis, Klebsiella spp., Haemophilus influenzae,
      Streptococcus pneumoniae, Streptococcus pyogenes and Enterobacter spp.

PMID- 12207128
TI  - Use of piritramide for analgesia and sedation during peribulbar nerve block for
      cataract surgery.
AB  - PURPOSE: To investigate the effects of pre-block analgesia and sedation using
      piritramide on haemodynamic stability, endocrine stress response and patients'
      pain perception. METHODS: In a randomized, single-blinded, placebo-controlled
      study, 60 patients having cataract surgery with peribulbar block were randomly
      assigned into two groups: group A (n = 30) received 0.05 mg/kg piritramide
      (Dipidolor) intravenously; group B received normal saline intravenously prior to
      peribulbar block. Mean arterial pressure, heart rate, respiratory rate and pulse
      oximetry were recorded perioperatively. Pain from peribulbar block was assessed
      using a verbal analogue scale. Urinary excretion of vanillylmandelic acid was
      measured to assess the endocrine stress response. Using a questionnaire, patients
      assessed their anxiety and back pain before and during surgery. RESULTS: Mean
      arterial pressure remained near baseline in group A. In group B, a significant
      increase in mean arterial pressure after peribulbar block was found (p < 0.001).
      In addition, a significant increase in urinary excretion of vanillylmandelic acid
      was found in group B (p = 0.013). Pain scores (p < 0.001), anxiety before nerve
      block (p = 0.02) and during surgery (p < 0.001) and back pain (p = 0.003) were
      significantly lower in group A. CONCLUSION: The presented study suggests that
      using piritramide for analgesia and sedation prior to peribulbar block produces
      haemodynamic stability and reduces pain perception and endocrine stress response.

PMID- 12207130
TI  - Plasma levels of endothelin-1 in retinitis pigmentosa.
AB  - Retinitis pigmentosa (RP) is an inherited retinal disorder clinically
      characterized by a pale, waxy optic nerve head, attenuated retinal blood vessels
      and bone spicule pigment in the retina. Hemodynamic studies have demonstrated
      that RP is associated with a reduction in the retinal and choroidal blood flow.
      Retinal hemodynamic impairment is also present in the early stages of RP and
      various hypotheses have been advanced as to its cause. The authors studied 20
      patients, 12 males and 8 females, aged between 26 and 42 years (mean 34.6 years)
      affected by simplex RP. The twenty patients were divided in two groups according
      to the degree of sight impairment: group A consisted of 10 patients with a visual
      acuity of 0.3 +/- 0.1, visual field mean defect 18.988 +/- 3.419 dB and b-wave
      electroretinogram amplitude of 13.14 +/- 0.308 microV. Group B consisted of 10
      patients with a visual acuity of 0.8 +/- 0.2, visual field MD 10.523 +/- 3.582 dB
      and b-wave electroretinogram amplitude of 26.000 +/- 0.757 microV. An increase in
      plasma levels of endothelin-1 (ET-1) was found as compared with healthy controls:
      1.910 +/- 0.617 pg/ml vs. 1.180 +/- 0.210 pg/ml (p < 0.021), but there was no
      statistical difference between group A and B (p < 0.163). It is thought that an
      increase in ET-1 and retinal oxygen levels in RP could lead to vasoconstriction
      and a decrease in the retinal blood flow worsening the abiotrophic process.

PMID- 12207131
TI  - Self-enucleation in drug-related psychosis.
AB  - OBJECTIVE: To report on a patient who committed self-enucleation with his own
      fingers. METHODS: Case report of a 28-year-old man who self-enucleated his right
      eye. After ophthalmological treatment, he was referred to the psychiatric
      department for further evaluation and treatment. RESULTS: Reconstruction of the
      orbit was performed, and neither ophthalmological nor neurological complications
      were noted. The psychiatric history revealed continuous drug abuse (cannabis and
      amphetamines). The diagnosis of a drug-induced psychosis was established.
      CONCLUSIONS: Self-enucleation or 'oedipism' is a rare entity which requires,
      besides an operative reconstruction of the orbit, neurological monitoring to
      prevent possible intracranial complications. Long-term psychiatric therapy should
      be attempted to prevent further self-injurious behaviour.

PMID- 12207132
TI  - Stenosis of the lachrymal system in Rubinstein-Taybi syndrome.
AB  - In this article the authors describe a case of atypical stenosis of the lachrymal
      excretory system in Rubinstein-Taybi syndrome (RTS) characterised by morphologic
      anomalies of the lachrymal bag and by alterations of the osseous structure of the
      nose. A 9-year-old girl, with typical findings of RTS, was affected by recurrent
      acute dacryocystitis and tearing. Ocular examination revealed bilateral reflux
      with mucous and purulent material flowing back after digital pressing: low and
      bilateral nose-lachrymal duct obstruction was the main cause of the reflux as
      confirmed by orifice probing, lachrymal drainage system irrigation and spiral CT
      examination using hydrosoluble contrast medium. The multiplanar reconstruction
      obtained from CT scanning shows that the right lachrymal sac has an abnormal
      shape ('grape-bunch' image) and that the left one has various bulgings, or
      swellings, in its shape. The 'grape-bunch' lachrymal bags are the most unusual
      features of our patient's lachrymal system and it is important to consider the
      difficulties that could occur during surgery because of the abnormal bag shape
      and because of the increased bone thickness in RTS patients. The 'grape-bunch'
      lachrymal sac is a truly unusual anatomical feature and, most probably, it could
      be distinctive of this syndrome.

PMID- 12207133
TI  - Orbital sinus histiocytosis (Rosai-Dorfman disease): a lacrimal gland
      involvement.
AB  - We report the clinical and histopathological features of 2 cases of orbital Rosai
      Dorfman disease with lacrimal gland involvement but no lymphadenopathy or
      cutaneous involvement. The first case was a 7-year-old boy, who was referred to
      the ophthalmology department with a proptosis in the left eye. The second case
      involved a 57-year-old African man, who developed oedema of the right upper
      eyelid over a 4-month period. Ocular involvement in Rosai-Dorfman disease is rare
      (10%). The diagnosis is histological in combination with immunohistology and is
      often delicate, especially in extranodal localizations. Histopathologically,
      normal gland morphology was altered by fibrosis and inflammatory cells. To our
      knowledge, this is the first report on lacrimal involvement in incomplete, thus
      uncommon sinus histiocytosis with massive lymphadenopathy.

PMID- 12207134
TI  - Choroidal neovascularization occurring concurrently in myopic eyes of monozygotic
      twins.
AB  - PURPOSE: To present young monozygotic twins both of whom developed choroidal
      neovascularization at the same time. CASE/OBSERVATIONS: Monozygotic twins, 22
      year-old women, who lived in the same house, developed choroidal
      neovascularization in the left eye at the same time. The degree of myopia was
      higher in the left eye (-7.75 and -8.5 dpt in spherical equivalent) than in the
      right eye (-6.75 and -4.5 dpt) of both patients. The choroidal neovascularization
      regressed in a different time course and the visual acuity returned to normal in
      both patients. CONCLUSION: This pair of monozygotic twins suggests that both
      genetic and environmental factors underlie the development of choroidal
      neovascularization in myopic eyes.

PMID- 12207135
TI  - Human connective tissue growth factor mRNA expression of epiretinal and
      subretinal fibrovascular membranes: a report of three cases.
AB  - PURPOSE: To investigate the correlation between connective tissue growth factor
      (CTGF) mRNA expression and immunohistochemical characteristics (expression of
      type I collagen and tenascin) of fibrovascular membranes of proliferative retinal
      diseases under in vivo conditions. METHODS: CTGF mRNA expression was investigated
      using in situ hybridization. Expression of type I collagen and tenascin was
      detected by immunohistochemical staining. RESULTS: CTGF mRNA is produced in
      transformed retinal pigment epithelial cells and appears also in fibroblast-like
      cells, which are embedded in epiretinal and subretinal membranes of proliferative
      retinal diseases as well as in surgically removed subretinal membranes. In all
      examined membranes, expression of human CTGF mRNA appears in concurrence with the
      expression of type I collagen and tenascin. CONCLUSIONS: The predominant
      expression of CTGF mRNA in the development of fibrovascular membranes of
      proliferative retinal diseases suggests a significant role of CTGF in the
      pathological course of these ocular disorders.

PMID- 12207136
TI  - Malignant transformation of optic disc melanocytoma? A clinical dilemma at
      presentation with a review of the literature.
AB  - Malignant transformation of optic disc melanocytoma is an uncommon feature,
      although in the past a few cases have been reported. Though our case, a healthy
      30-year-old female, presented with all clinical features of melanocytoma, the
      triad of moderate visual loss, elevation of the lesion of 5.2 mm and an atypical
      ultrasonic picture could be an indication of malignant change at presentation. In
      the event of a moderate visual loss, long-term follow-up with serial fundus
      photographs and ultrasonic measurements is necessary for further management.

PMID- 12207137
TI  - Pseudotumor cerebri in a patient with Goldenhar's and Duane's syndromes.
AB  - A 4-year-old boy presented with Goldenhar's syndrome, Duane's syndrome and
      bilateral papilledema. Magnetic resonance imaging of the brain was unremarkable.
      On lumbar puncture, the cerebrospinal fluid (CSF) pressure measured 36 cm H(2)O.
      CSF examination was normal. The diagnosis of pseudotumor cerebri was made, and
      treatment with acetazolamide was started. As the papilledema did not resolve,
      steroids were added to the treatment. Lumbar puncture was repeated after 1 month,
      and pressure was found to be 30 cm H(2)O. Because medical treatment was not
      effective in lowering the CSF pressure, optic nerve sheath fenestration was
      performed. Papilledema resolved over the next 2 months. To the best of our
      knowledge, this is the first case of Goldenhar's syndrome associated with
      pseudotumor cerebri.

PMID- 12207138
TI  - Disseminated hydatid disease involving orbit, spleen, lung and liver.
AB  - Orbital hydatid disease is rare, even in endemic areas. We present a case of
      disseminated hydatid disease involving the orbit, spleen, lung and liver in a
      lady aged 35 years. Based on a typical clinical presentation, presence of
      eosinophilia, a positive indirect haemagglutination test for hydatid disease and
      presence of similar disseminated, anechoic cystic masses in the liver, lung,
      spleen and orbit on imaging studies, the diagnosis of hydatid cyst was seriously
      considered before surgery. Aspiration of the cyst, followed by cryo-extraction of
      the cyst wall through transconjunctival route was safely performed.
      Histopathological examination confirmed the diagnosis. In conclusion,
      multisystemic involvement of liver, lung and spleen in a case of orbital hydatid
      cyst has never been reported before. The surgical technique adopted in this case
      is safe and effective.

PMID- 12207139
TI  - Twenty-four-hour QT interval variability: increased QT variability during sleep
      in patients with panic disorder.
AB  - Recent studies on beat-to-beat QT interval variability (QTV) have shown that it
      can be used as a noninvasive measure of cardiac repolarization lability. It is
      also a predictor of sudden cardiac death and is higher in patients with anxiety
      and depression. This study examined the diurnal measures in QTV in 32 normal
      adults and 22 patients using 24-hour electrocardiogram records. We obtained 8 5
      min segments of ECG sampled at 1,000 Hz from the 24-hour records. Our results
      show that QTV measures at nighttime are significantly higher in patients with
      panic disorder compared with controls. These findings demonstrate blunted diurnal
      changes in ventricular repolarization lability in patients resulting in a higher
      QT variability index during sleep. We speculate that these effects may relate to
      a relative increase in cardiac sympathetic activity in patients with panic
      disorder, and may contribute to the increased risk for cardiac mortality in
      patients with anxiety.

PMID- 12207140
TI  - Schizophrenic patients who develop postoperative confusion have an increased
      norepinephrine and cortisol response to surgery.
AB  - The purpose of this study was to investigate the relationship between
      postoperative confusion and the plasma norepinephrine (NE), adrenocorticotropin
      (ACTH) or cortisol response to surgery in schizophrenic patients. We studied 50
      schizophrenic patients and 35 control patients who underwent orthopedic surgery
      and perioperatively measured plasma NE, ACTH and cortisol levels. Postoperative
      confusion during 72 h after the end of the operation occurred in 14 of 50
      schizophrenic patients (28%) and in 2 of 35 control patients (6%). Plasma NE
      levels 15 min after skin incision, the next day, the second day and the third day
      after operation in schizophrenic patients with postoperative confusion (668.0 +/-
      59.2, 522.0 +/- 96.5, 463.2 +/- 71.2 and 398.9 +/- 56.2 pg/ml, respectively) were
      significantly higher than those in schizophrenic patients without confusion
      (524.1 +/- 62.6, 342.4 +/- 38.6, 311.2 +/- 58.3 and 314.1 +/- 77.1 pg/ml,
      respectively). Plasma cortisol levels 15 min after the skin incision and the next
      and second days after operation in schizophrenic patients with postoperative
      confusion (23.6 +/- 3.2, 21.1 +/- 4.3 and 19.9 +/- 4.4 microg/dl, respectively)
      were significantly higher than those in schizophrenic patients without confusion
      (15.2 +/- 4.5, 14.3 +/- 5.1 and 13.8 +/- 3.8 microg/dl, respectively). In
      conclusion, the occurrence of postoperative confusion in schizophrenic patients
      is associated with an increase in plasma norepinephrine and cortisol levels
      during and after surgery.

PMID- 12207141
TI  - Brain perfusion in autism varies with age.
AB  - Our subjects consisted of 14 autistic individuals and 14 controls ranging in age
      from 3 to 37 years. A (99m)Tc HMPAO single photon emission computed tomogram
      (SPECT) was used to examine blood flow variations between autistic subjects,
      compared to an age- and gender-matched control group. We found significant
      hypoperfusion in the prefrontal areas of autistic individuals as compared to
      normals in every case (p < 0.01). As the age of the autistic individuals
      increased the hypoperfusion of verbal-associated areas in the left temporal lobe
      and frontal areas became more evident. The findings were significant at the p <
      0.001 level. The changes in perfusion over time correlated with language
      development and acquisition as individuals matured. We conclude that autistic
      individuals have a deficiency in prefrontal areas associated with word
      identification and language formation skills. This subsequently prevents
      development of true verbal fluency and development in the temporal and frontal
      areas associated with speech and communication.

PMID- 12207142
TI  - Allelic variation in the human prodynorphin gene promoter and schizophrenia.
AB  - Experimental and clinical studies suggest an involvement of the opioid
      neuropeptide system in schizophrenia. In particular, the prodynorphin (PDYN), the
      precursor of the dynorphin opioid peptides, has been shown to play an important
      role in several aspects of human mental diseases. Recently, a functional
      polymorphism in the promoter of PDYN gene has been described. We studied the
      possible relationship between this polymorphism and schizophrenia and we found no
      significant difference in allelic and genotype distributions between
      schizophrenic patients and control subjects. However, we observed a significant
      interactive effect with the receptor 3 of dopamine gene (DRD3); in particular,
      the frequency of subjects carrying PDYN allele 3 being also homozygotes for DRD3
      Gly allele (of Ser9Gly polymorphism) was significantly greater in patients than
      controls. We conclude that PDYN gene polymorphism alone does not alter the risk
      for schizophrenia but, by an epistatic interaction with the Gly allele of DRD3
      gene, may contribute to the susceptibility to this disorder.

PMID- 12207143
TI  - Cortisol response to surgery and postoperative confusion in depressed patients
      under general anesthesia with fentanyl.
AB  - The purpose of this study was to investigate the relationship between
      postoperative confusion and plasma cortisol response to surgery in depressed
      patients. We studied 80 depressed patients and 40 control patients who had
      undergone orthopedic surgery and perioperatively measured plasma cortisol and
      adrenocorticotropin levels. Postoperative confusion in the first 3 postoperative
      days occurred in 5 (13%) depressed patients given fentanyl during anesthesia, 13
      (33%) patients without fentanyl and 1 (3%) control patients. Plasma cortisol
      concentration (19.7 +/- 6.9 and 19.2 +/- 8.0 microg dl(-1)) 15 min after skin
      incision and 60 min after the end of surgery in depressed patients with fentanyl
      was significantly lower than that (24.2 +/- 7.2 and 23.5 +/- 8.1 microg dl(-1))
      of depressed patients without fentanyl. Plasma cortisol levels during and after
      surgery in depressed patients with postoperative confusion were higher than those
      of depressed patients without postoperative confusion. We conclude that the
      occurrence of postoperative confusion in depressed patients is associated with an
      increase in plasma cortisol levels during and after surgery. The incidence of
      postoperative confusion in depressed patients with fentanyl was significantly
      lower than that of depressed patients without fentanyl.

PMID- 12207144
TI  - Antioxidant enzyme activities and malondialdehyde levels in patients with
      obsessive-compulsive disorder.
AB  - To examine the importance of free radicals in the pathogenesis of obsessive
      compulsive disorder (OCD), we aimed to evaluate whether malondialdehyde (MDA), a
      product of lipid peroxidation, and antioxidant enzyme [superoxide dismutase
      (SOD), glutathione peroxidase (GSH-Px) and catalase (CAT)] activity levels were
      associated with OCD. The patients were divided into two subgroups according to
      whether DSM-IV major depressive disorder (MDD) was accompanied (OCD + MDD) or not
      (OCD - MDD). The MDA and antioxidant enzyme levels both in patients and controls
      were determined. SOD activity levels were significantly higher in the OCD + MDD
      group compared with the control and the OCD - MDD group. Although the OCD - MDD
      group had slightly higher SOD activity levels as compared with the controls, the
      difference was not statistically significant. GSH-Px activity levels were
      statistically significantly higher in both groups compared with controls.
      Likewise, there was a significant difference in GSH-Px activity levels between
      the OCD + MDD and OCD - MDD group. CAT activity levels were slightly higher in
      the OCD + MDD group compared with the OCD - MDD and control group. MDA levels in
      both groups were significantly higher than in controls. In addition, the
      difference in MDA levels between both groups was statistically significant. In
      conclusion, our results suggest that OCD is associated with free radicals and
      that it may be a heterogeneous subtype including some biological indications of
      anxiety and affective disorders. More comprehensive and detailed studies are
      needed to decipher the exact role of free radicals in OCD.

PMID- 12207145
TI  - Long-term effects of the substituted benzamide derivative amisulpride on baseline
      and stimulated prolactin levels.
AB  - In the present study, we investigated the long-term effects of treatment with
      amisulpride, a substituted benzamide derivative, as compared with the effects of
      treatment with flupenthixol, a thioxanthene, on the prolactin levels in
      schizophrenic patients. After completing 6 weeks of medication with either
      amisulpride or flupenthixol, the patients entered a long-term maintenance
      treatment with amisulpride 200-600 mg/day or flupenthixol 5-15 mg/day for a
      maximum of 12 months with a subsequent drug-free follow-up until month 15.
      Eighteen initially included patients were still participating in the study at
      month 6. In the flupenthixol group, only 1 patient treated reached month 12, and
      none of the patients reached month 15. For the amisulpride treatment group,
      months 12 and 15 were completed by 9 and 6 patients, respectively. After 1, 3, 6,
      and 12 months of treatment, and finally 3 months after cessation of treatment,
      the basal and thyrotropin-releasing hormone-stimulated secretions of prolactin
      were investigated. The prolactin plasma levels were elevated in both treatment
      groups during the course of maintenance treatment with a maximum effect at month
      1. Flupenthixol treatment initially raised the prolactin levels about two- or
      threefold, and a subsequent decline during months 3 and 6 occurred. However, only
      the changes for month 1 reached the level of a statistical trend. The prolactin
      secretion was initially increased over tenfold by amisulpride. The prolactin
      levels at months 1, 3, 6, and 12 were significantly elevated as compared with the
      baseline values. A continuous decline of prolactin levels in both treatment
      groups occurred over the course of the next months. The prolactin response after
      the thyrotropin-releasing hormone challenge was not significantly changed over
      the long-term course. Notably, in the amisulpride group, 3 months after cessation
      of treatment at month 12, the elevated levels of prolactin returned to baseline
      at month 15. In summary, amisulpride demonstrated more pronounced effects than
      flupenthixol on the prolactin levels. However, the findings indicate also that
      treatment with amisulpride at clinically effective doses can be achieved at
      significantly lower prolactin levels during the long-term maintenance phase than
      during the prior acute phase.

PMID- 12207146
TI  - Impact of cortisol on emotions under stress and nonstress conditions: a
      pharmacopsychological approach.
AB  - Although the importance of the hypothalamic-pituitary-adrenal axis in emotional
      stress response is a well-established fact, the causal relationship between
      glucocorticoids and emotions remains unclear. Therefore, it was tried to
      elucidate this relationship by an experimental approach in 100 healthy
      volunteers. The effects of different oral dosages of cortisol (hydrocortisone; 20
      and 40 mg) or placebo on emotional states were tested under stress and nonstress
      conditions in an independent group design. Furthermore, the time of drug
      application was varied in relation to the onset of the stress/nonstress
      conditions (1 vs. 2 h prior to exposure). Stress and nonstress conditions were
      induced by a film depicting violence and neutral scenes, respectively. The
      results indicate that the application of cortisol ameliorates emotional states
      irrespective of the time of drug administration and stress exposure. Also the
      dimensions of activity were increased by cortisol in all experimental conditions,
      except when applied 1 h before stress onset, indicating an adaptive negative
      feedback regulation preventing stress-induced overactivation.

PMID- 12207147
TI  - Quantitative EEG changes in Alzheimer patients during long-term donepezil
      therapy.
AB  - Twenty patients affected with probable mild-to-moderate Alzheimer's disease (AD;
      NINCDS-ADRDA criteria; 14 women and 6 men, mean age 75.2 +/- 7.1 years) who
      regularly received an oral acetylcholinesterase inhibitor (AChEI; donepezil 5
      mg/day; Dz group) were compared with a control group of 11 AD patients (6 women
      and 5 men, mean age 73.5 +/- 6.0 years) diagnosed and followed up in the pre
      AChEIs era (C group). At basal evaluation (t(0)), the 2 groups were comparable
      for age, education, and severity of disease (Global Deterioration Scale). All
      patients underwent quantitative EEG (qEEG, average reference, 10-20 International
      System), and were reexamined about 1 year later (t(1); i.e., after 12.3 +/- 3.6
      months the Dz group, and after 13.7 +/- 3.9 months the C group). Log-transformed
      values of two qEEG bands, i.e. 2-6 and 6.5-12 Hz, were averaged between adjacent
      channels (frontal F3 and F7, F4 and F8; parietotemporal P3 and T7, P4 and T8) to
      obtain a qEEG ratio (6.5-12/2-6 Hz.) from one frontal and one temporoparietal
      region in each hemisphere. Neuropsychological impairment was summarized by the
      Mini-Mental Status Examination (MMSE). At t(0), both the MMSE score and the qEEG
      ratio values were somewhat higher in the C than in the Dz group, although
      nonsignificantly. Between t(0) and t(1), the MMSE score decreased significantly
      (p < 0.01) more in the C group (-4.36 +/- 2.25) than in the Dz group (-1.45 +/-
      2.16), as did the qEEG ratio in the right frontal region (p < 0.01), whereas in
      the left frontal region the significance level was not reached (p = 0.02).
      Between t(0) and t(1), the qEEG ratio difference in both frontal regions and in
      the right temporoparietal region significantly correlated with the MMSE
      difference (p < 0.01), but neither with time between examinations nor with the
      difference on the Visual Search Test score. Long-term treatment with Dz led to a
      lesser deterioration of qEEG, paralleling a milder neuropsychological decline.
      The effect was significant in frontal regions, possibly because they are
      relatively spared during the mild-to-moderate phases of the disease.

PMID- 12207148
TI  - Prevalence of disorders of executive cognitive functioning among the elderly:
      findings from the San Luis Valley Health and Aging Study.
AB  - The San Luis Valley Health and Aging Study is a population-based epidemiologic
      study of chronic illness and disability among Hispanic and non-Hispanic white
      persons over the age of 60 in two counties in rural southern Colorado, USA.
      Between 1993 and 1995, we examined the prevalence of impaired executive cognitive
      functioning in a sample of 1,313 individuals living both in the community and in
      nursing homes. Overall, 1 person in 3 was found to have at least mild impairment,
      while 1 in 6 had moderate to severe deficits. Increasing levels of executive
      functioning impairment were associated with lower education, advancing age, and
      Hispanic ethnicity. After controlling for education and acculturation, the
      differences by ethnic group were no longer significant.

PMID- 12207149
TI  - Epidemiology of myasthenia gravis: a population-based study in Stockholm, Sweden.
AB  - A regional database of myasthenia gravis (MG) patients was used to estimate the
      prevalence and selected characteristics of the disease in the county of
      Stockholm, Sweden. The prevalence of MG was 14.1/100,000 (17.1 for women and 10.8
      for men). The mean age at onset for women and men was 34.9 and 48.5 years,
      respectively. About 60% of patients were diagnosed within the first year after
      initial symptoms. Generalized MG was found in 79% of patients, and 10% had severe
      symptoms. Almost two thirds of the patients had undergone thymectomy, and 30%
      needed immunosuppressive treatment. The increase in the prevalence of MG since
      the 1960s probably reflects an improvement in prognosis and higher detection
      rates of patients with milder symptoms. A delay in diagnosis indicates that early
      signs and symptoms of MG are still not well known by all doctors.

PMID- 12207150
TI  - Prevalence of multiple sclerosis in Austria. Results of a nationwide survey.
AB  - The epidemiology of multiple sclerosis (MS) in Austria is almost unknown. We
      evaluated the prevalence of MS in Austria using data from questionnaires
      completed by neurologists, comprising information on a total of 1,006 MS patients
      who attended 30 out-patient specialized clinics nationwide. Additional data were
      collected from 2,414 MS patients, who received questionnaires from the Austrian
      MS Society or their doctor. A novel extrapolation model, based on frequencies of
      patients visits at MS clinics, was used to estimate the overall prevalence of MS.
      Considering either disability or the course of the disease, the prevalence of MS
      patients in Austria was estimated to be 98.5 per 100,000 people. The prevalence
      of MS in Austria was found to be similar to that of other countries in Central
      Europe. Epidemiological studies, such as this, provide a unique source of data
      from which key features of a disease and its impact on patients may be examined.

PMID- 12207151
TI  - Survival of multiple sclerosis patients in the Belgrade population.
AB  - The aim of this study was to estimate survival rates of multiple sclerosis (MS)
      patients in the Belgrade population, Yugoslavia, and furthermore, to determine
      the prognostic value of some demographic and clinical variables for survival. The
      cumulative survival probability was calculated by the Kaplan-Meier method. The
      prognostic value of different variables was assessed by univariate and
      multivariate analyses using the Cox regression model. In the Belgrade population,
      the cumulative 25-year survival probability of MS patients and the mean survival
      time from MS onset were 73.2% and 38 years, respectively. The univariate analysis
      showed that survival was significantly related to sex, age at onset, course of
      disease and monoregional initial symptoms. A multivariate model demonstrated that
      a relapsing-remitting course of MS and monoregional onset were predictors of a
      better prognosis. The presence of motor symptoms at the onset was found to be an
      independent predictor of a poorer outcome of MS.

PMID- 12207152
TI  - Charcot-Marie-Tooth disease in Molise, a central-southern region of Italy: an
      epidemiological study.
AB  - An epidemiological survey of Charcot-Marie-Tooth disease (CMT) was conducted in
      Molise, a central-southern region of Italy, from March 1998 to June 2000. Fifty
      eight cases of CMT in 13 unrelated families were identified within the selected
      area. The prevalence of all subtypes of CMT was 17.5/100,000. All families
      underwent a bio-molecular analysis to disclose the duplication at gene locus
      17p11.2 in order to ascertain the diagnosis of CMT type 1A. Our data revealed
      that 64% of all the observed patients had CMT1A, thus confirming the high
      prevalence of duplication of the 17p11.2 locus.

PMID- 12207153
TI  - An epidemiological genetic study of Charcot-Marie-Tooth disease in Western Japan.
AB  - We identify the prevalence and genetic features of Charcot-Marie-Tooth disease
      (CMT) in Yonago and Sakaiminato, western Japan. From information in registered
      records and questionnaires, definite or candidate CMT patients were examined.
      Eleven families with 19 patients (7 female and 12 male) were identified and the
      prevalence was 10.8 per 100,000 in April 2000. Eleven patients in 6 families
      showed a Thr124Met mutation of the MPZ gene, in 2 families duplication of the
      PMP22 gene was suggested and no abnormalities were found in 2 families. To
      identify the occurrence of mildly affected CMT, the exhaustive region-matched and
      family study was necessary.

PMID- 12207154
TI  - Risk factors for cryptogenic and idiopathic partial epilepsy: a community-based
      case-control study in Copparo, Italy.
AB  - OBJECTIVES: The etiology of epilepsy remains unknown in most cases. We sought to
      investigate the role of some pre-, peri- and postnatal factors in the etiology of
      idiopathic and cryptogenetic partial epilepsy. METHODS: We carried out a
      community-based case-control study using the incidence cohort of epileptic
      patients living in the district of Copparo, in the province of Ferrara, Italy.
      The study was performed in 55 cases and 165 controls. A standardized
      questionnaire was used to collect information in face-to-face interviews.
      RESULTS: Multivariate logistic regression analysis found that a personal history
      of febrile convulsions [odds ratio (OR) = 4.01, 95% confidence interval (CI) =
      1.3-19.1] and a family history of seizures in first-degree relatives (OR = 4.5,
      95% CI = 1.8-18.6) were independent risk factors for the condition under study.
      We failed to demonstrate an association between partial epilepsy and previously
      suggested perinatal risk factors. CONCLUSION: The findings of this study further
      support the hypothesis of a genetic propensity for seizures, which may be
      expressed early by the occurrence of febrile convulsions.

PMID- 12207155
TI  - Annualized incidence and spectrum of illness from an outbreak investigation of
      Bell's palsy.
AB  - BACKGROUND: There are limited clinical and epidemiological data on patients
      diagnosed with Bell's palsy. While investigating an apparent clustering of Bell's
      palsy, we sought to characterize the spectrum of illness in patients with this
      diagnosis. METHODS: A telephone survey of persons with idiopathic facial (Bell's)
      palsy in the Greater Toronto Area (GTA, population = 4.99 million) and Nova
      Scotia (population = 0.93 million) from August 1 to November 15, 1997 collected
      information on subject demographics, neurological symptoms, constitutional
      symptoms, medical investigation and management. Information regarding potential
      risks for exposure to infectious agents, past medical history, and family history
      of Bell's palsy was also collected. Subjects with other secondary causes of
      facial palsy were excluded. RESULTS: In the GTA and Nova Scotia, 222 and 36
      patients were diagnosed with idiopathic facial (Bell's) palsy, respectively. The
      crude annualized incidence of Bell's palsy was 15.2 and 13.1 per 100,000
      population in the GTA and Nova Scotia, respectively. There was no temporal or
      geographical clustering, and symptomatology did not differ significantly between
      the two samples. The mean age was 45 years, with 55% of subjects being female.
      The most common symptoms accompanying Bell's palsy were increased tearing (63%),
      pain in or around the ear (63%), and taste abnormalities (52%). A significant
      number of patients reported neurological symptoms not attributable to the facial
      nerve. CONCLUSION: No clustering of cases of Bell's palsy was observed to support
      an infectious etiology for the condition. Misdiagnosis of the etiology of facial
      weakness is common. Patients diagnosed with Bell's palsy have a variety of
      neurological symptoms, many of which cannot be attributed to a facial nerve
      disorder.

PMID- 12207157
TI  - Preferential survival of an MBP-specific T cell clone in an HLA-DR2 multiple
      sclerosis patient.
AB  - Anti-myelin basic protein (MBP) autoreactive T cells play a key role in the
      pathogenesis of multiple sclerosis. Thus, we applied the Immunoscope strategy to
      cerebrospinal fluid (CSF) and peripheral blood lymphocytes (PBLs) of an HLA-DR2
      patient. Both compartments showed major expansion for the V(beta)13S5 chain,
      which was associated in peripheral blood with significant proliferation of PBLs
      in response to MBP and the 84-102 HLA-DR2-restricted peptide. Sequencing revealed
      a unique nucleotide sequence in the CSF that gives rise to the amino acid
      sequence V(beta)13S5-RPGQGDQETQ-J(beta)2.5 if translated. This CDR3 sequence had
      already been reported to be reactive against the 84-102 peptide. This specific
      sequence was not detected in PBLs on day 0, whereas it was readily detectable on
      day 6 culture samples. Thus, cell culture may lead to enrichment in a T cell
      clone identified as autoreactive.

PMID- 12207158
TI  - The analgesic domain of interferon-alpha2b contains an essential proline(39)
      residue.
AB  - OBJECTIVE: It has been demonstrated that there are structural and functional
      similarities between interferon-alpha (INF-alpha) and endorphins. We have
      reported that there are distinct domains in the IFN-alpha molecule that mediate
      immune and analgesic effects, respectively, and that the opioid-like analgesic
      effect of IFN-alpha is mediated by the mu opioid receptor, thus inferring that
      the analgesic domain of IFN-alpha consists of Tyr(122) and the residues around
      Tyr(122) in the tertiary structure. The aim of this work was to further explore
      the molecular basis for the analgesic domain of IFN-alpha. METHODS: By using site
      directed mutagenesis, the structure of IFN-alpha was changed and a mutant of IFN
      alpha was obtained. Then, the antiviral activity and opioid-like analgesic
      activity of IFN-alpha were measured. RESULTS: When the Pro(39) residue of IFN
      alpha, which is located close to the Tyr(122) residue in the tertiary structure,
      was mutated to Gly, the analgesic activity of this mutant was lost completely,
      but the antiviral activity of IFN-alpha was maintained compared with wild-type
      IFN-alpha. CONCLUSIONS: Combining the sequence of the endomorphin, it is
      suggested that the Pro(39) residue is one of the constituents of the analgesic
      domain of IFN-alpha and contributes to IFN-alpha binding to the mu opioid
      receptor.

PMID- 12207159
TI  - Function of the hypothalamo-pituitary-adrenal axis and humoral immune mechanisms
      during experimental allergic encephalomyelitis in SJL/J mice.
AB  - OBJECTIVES: In the present work, a method to induce experimental allergic
      encephalomyelitis (EAE) in female SJL/J mice was developed and validated in our
      laboratory. Although the latter is a popular animal model to mimic human multiple
      sclerosis, it remains to be clarified if: (1) the measurement of circulating
      antibodies against myelin antigens can be used as an index to predict the
      development of clinical EAE, as well as the severity of disease, and (2) the
      genetic susceptibility of this strain is associated with altered hypothalamo
      pituitary-adrenal (HPA) function. METHODS AND RESULTS: We observed that SJL/J
      mice display a strong humoral response to immunization with myelin basic protein
      (MBP), as assessed by the titration of circulating anti-MBP antibodies. However,
      there was no apparent correlation between the presence and amount of circulating
      antibodies and the occurrence or severity of disease. Concerning the
      responsiveness of the HPA axis, we observed that circulating corticosterone
      levels are not modified at all during the induction of EAE, whereas an increase
      is observed at a later stage of the disease. CONCLUSIONS: The above profile is
      strongly reminiscent of the HPA axis response to the induction of EAE in Lewis
      rats, suggesting that the susceptibility of SJL/J mice to EAE may similarly be
      caused, at least in part, by blunted HPA reactivity to immune challenges.

PMID- 12207160
TI  - Inhibitory effect of neurogenic and immune stressors on testosterone secretion in
      rats.
AB  - OBJECTIVE: We investigated the ability of foot shocks, endotoxemia and turpentine
      induced tissue injury, to interfere with luteinizing hormone (LH) and
      testosterone (T) secretion, and the putative role of beta-adrenergic, opiate- and
      corticotropin-releasing factor (CRF) receptors in these responses. METHODS: Adult
      male rats were exposed to mild intermittent foot shocks for 1 h, administered
      endotoxin [lipopolysaccharide (LPS)] intravenously (i.v., 5 microg/kg), or
      injected with turpentine intradermally (i.m., 400 microl/kg), prior to injection
      with human chorionic gonadotropin (hCG, 1 U/kg i.v.). In some cases, antagonists
      to CRF, adrenergic or opiate receptors, or their vehicle were administered prior
      to the stressors. Levels of LH, T, tumor necrosis factor-alpha (TNF-alpha),
      interleukin-6 (IL-6), adrenocorticotropin (ACTH) and/or corticosterone were
      measured in serial blood samples. RESULTS: All three challenges significantly
      lowered basal LH and T levels and blunted the T response to hCG, though the
      magnitude of this inhibition was significantly (p < 0.01) smaller in shocked rats
      (42%), compared to animals injected with LPS (92%) or turpentine (78%). Shocks,
      LPS and turpentine all significantly stimulated ACTH and corticosterone release,
      and the magnitude and time course of these responses were also stressor specific.
      While turpentine only increased circulating IL-6 concentrations, shocks and LPS
      both significantly increased circulating TNF-alpha and IL-6 levels, but the
      effect of shocks was markedly smaller. Pretreatment with propranolol did not
      restore T responses, while naloxone produced small and inconsistent effects.
      However, the CRF antagonist Astressin B, which significantly prevented stressor
      induced increase in circulating levels of ACTH and corticosterone, partially
      reversed the inhibitory effect of LPS on hCG-induced T release. CONCLUSION: (1)
      Both neurogenic and systemic stressors lower basal plasma LH and T levels and
      blunt the T response to hCG. (2) LPS, whose ability to release ACTH and
      corticosterone was similar to that of shocks, but caused increases in circulating
      TNF-alpha and IL-6 levels that were significantly larger than those due to the
      other stressors, was the most potent inhibitor of the T response to hCG. (3)
      Neither beta-adrenergic nor opiate receptors play a major role in the ability of
      the stressors we used to inhibit T release.

PMID- 12207161
TI  - Lipopolysaccharide- and tumor necrosis factor-alpha-induced changes in prolactin
      secretion and dopaminergic activity in the hypothalamic-pituitary axis.
AB  - Bacterial lipopolysaccharide (LPS) affects pituitary hormone secretion, including
      prolactin release, by inducing synthesis and release of cytokines such as tumor
      necrosis factor-alpha (TNF-alpha). Since prolactin is mainly under tonic
      inhibitory control of dopamine, we investigated the effect of LPS and TNF-alpha
      on the hypothalamic-pituitary dopaminergic system. LPS (100-250 microg/rat, i.p.)
      decreased serum prolactin levels after 1 or 3 h. Sulpiride, a dopaminergic
      antagonist, increased serum prolactin and blocked the inhibitory effect of LPS.
      LPS increased hypothalamic dopamine and DOPAC concentrations and the
      DOPAC/dopamine ratio both in mediobasal hypothalamus and the posterior pituitary.
      LPS also enhanced dopamine and DOPAC concentration in the anterior pituitary. LPS
      elevated plasma levels of epinephrine, norepinephrine and dopamine but it did not
      modify the concentration of epinephrine or norepinephrine in the tissues studied.
      The administration of TNF-alpha (i.c.v., 1 h, 100 ng/rat) decreased serum
      prolactin but did not affect plasma catecholamine levels. TNF-alpha did not
      modify the DOPAC/dopamine ratio in hypothalamus or posterior pituitary but
      increased dopamine and DOPAC concentrations in the anterior pituitary.
      Incubations of hypothalamic explants showed that TNF-alpha did not modify in
      vitro basal dopamine release and reduced K(+)-evoked dopamine release. On the
      contrary, incubations of posterior pituitaries showed that TNF-alpha
      significantly increased basal and K(+)-evoked dopamine release. These results
      indicate that LPS and TNF-alpha increase dopamine turnover in the hypothalamic
      pituitary axis. This increase in dopaminergic activity could mediate the
      inhibitory effect of LPS and TNF-alpha on prolactin release. Furthermore, the
      increase in dopaminergic activity elicited by LPS could be mediated by an
      increase in hypothalamic TNF-alpha during endotoxemia.

PMID- 12207162
TI  - Attenuation of LPS-induced changes in synaptic activity in rat hippocampus by
      Vasogen's Immune Modulation Therapy.
AB  - Systemic injection of lipopolysaccharide (LPS) blocks the expression of long-term
      potentiation in the hippocampus of the rat. This is coupled with increased IL
      1beta concentration and c-Jun NH(2)-terminal kinase activity, as well as an
      increase in the number of cells displaying apoptotic characteristics in the
      hippocampus. Vasogen's Immune Modulation Therapy (IMT) is a procedure involving
      intramuscular administration of syngeneic blood which has been exposed ex vivo to
      elevated temperature, oxidation and ultraviolet light. We report that Vasogen's
      IMT significantly abrogates these LPS-induced effects with a concomitant increase
      in the concentration of the anti-inflammatory cytokine IL-10. These data suggest
      that Vasogen's IMT may play a protective role against the deleterious effects of
      immune insults in the brain.

PMID- 12207163
TI  - Molecular and cellular basis of isolated dominant-negative growth hormone
      deficiency, IGHD type II: insights on the secretory pathway of peptide hormones.
AB  - Estimates of the frequency of GH deficiency range from 1:4,000 to 1:10,000. Most
      cases are sporadic and presumed to be secondary to a wide variety of aetiologies.
      However, in families with consanguinity, or when a second case occurs in the same
      family, a genetic cause may be suspected. Given that the patient is isolated GH
      deficient four distinct familial types of isolated GH deficiencies (IGHD) are
      well-differentiated on the basis of inheritance, hormonal deficiencies as well as
      molecular analyses. Two forms are autosomal recessively (IGHD type IA and IB),
      one is autosomal dominantly (IGHD type II) and one X-linked inherited. In this
      review, we focus on the secretory pathway of peptide hormones in general and on
      the possible mechanisms causing IGHD type II in detail. Most interestingly, in
      IGHD type II the apparently same phenotype of IGHD is caused by distinct GH-1
      gene alterations leading to different blockades within the secretory pathway.
      Furthermore, this type of IGHD, in addition to some other specific GH-1 gene
      mutations, provides the most important opportunity to shed light on cell
      biological mechanisms far beyond its pure description at the DNA/RNA level.

PMID- 12207164
TI  - Plasma soluble intercellular adhesion molecule 1 levels are increased in type 2
      diabetic patients with nephropathy.
AB  - BACKGROUND/AIM: Intercellular adhesion molecule 1 (ICAM-1) is a mediator in the
      recruitment of leukocytes in the glomerular cells. The role of ICAM-1 in diabetic
      complications is still a matter of debate. This study was performed to
      investigate the relation of plasma soluble ICAM-1 (sICAM-1) to nephropathy in
      patients with type 2 diabetes mellitus. METHODS: Ninety-three patients (24 males
      and 69 females) with type 2 diabetes mellitus were included into the study. Fifty
      patients had nephropathy, and 43 were free from nephropathy. Fifty healthy
      subjects (14 males and 36 females) served as the control group (group 1). Twenty
      five of the diabetic patients had microalbuminuria (group 2), 25 had
      macroalbuminuria (group 3), and 43 had neither micro- nor macroalbuminuria (group
      4). The plasma sICAM-1 levels were measured in blood samples drawn after fasting.
      RESULTS: The mean plasma sICAM-1 levels were not different in the 93 diabetic
      patients as compared with the healthy controls (392.7 +/- 119.5 vs. 350.1 +/-
      90.2 ng/ml, p > 0.05). The mean sICAM-1 level was significantly higher in the
      diabetic patients with nephropathy than in those without nephropathy (430.3 +/-
      78.2 vs. 368.2 +/- 122.5 ng/ml, p = 0.03) and in the controls (430.3 +/- 78.2 vs.
      350.1 +/- 90.2 ng/ml, p = 0.016). The difference in sICAM-1 levels between groups
      2 and 3 was not significant (p > 0.05). The plasma sICAM-1 levels were
      significantly higher in both groups 2 and 3 than in both groups 1 and 4 (434.5 +/
      129.2 vs. 427.2 +/- 113.7 ng/ml and 368.2 +/- 122.5 vs. 350.1 +/- 90.2 ng/ml,
      respectively). CONCLUSIONS: The plasma sICAM-1 levels in patients with type 2
      diabetes mellitus are not significantly different from those in nondiabetic
      subjects. High levels of sICAM-1 suggest that sICAM-1 may play a role in the
      development of nephropathy in patients with type 2 diabetes mellitus.

PMID- 12207165
TI  - Short-term growth response to GH treatment and considerations upon the limits of
      short-term growth predictions.
AB  - OBJECTIVES: To investigate the impact of short-term growth measurements on
      predicting the individual growth response to GH treatment, and to elucidate the
      possible reasons for the limited accuracy of current growth prediction models for
      GH-treated children. METHODS: Short-term growth measurements by knemometry and
      stadiometer in 99 short, GH-treated children (27 girls, 72 boys), aged 10.3 +/-
      2.3 years, from the Children's University Hospital, Leipzig, Germany. RESULTS: GH
      treatment significantly accelerated the mean height velocity (HV) from 4.3 +/-
      1.0 to 8.1 +/- 1.8 cm/year during the first year of treatment, the average height
      standard deviation score (SDS) shifted by +0.52 SD. The variation in HV also
      increased, from S(2) = 1.0 before to S(2) = 3.4 cm(2)/year(2) during treatment.
      Lower leg length (LLL) velocity accelerated from 1.6 +/- 0.7 before treatment to
      3.4 +/- 1.0 cm/year during the first 8 weeks of treatment. Four coefficients of
      correlation appeared clinically meaningful: (1) LLL velocity vs. body HV during
      the first year of GH treatment (r = 0.87), indicating that GH acts simultaneously
      on leg and rump growth; (2) early (first 8 weeks) LLL velocity vs. 1-year body HV
      during treatment, with r = 0.61 (R(2) = 0.38), indicating that 38% of the
      variation in HV during the first year of treatment is already predictable by an
      initial 8-week period of knemometry; (3) early (first 8 weeks) LLL velocity vs. 1
      year LLL velocity during treatment, with r = 0.63 (R(2) = 0.39), and (4) early
      (first 8 weeks) LLL velocity vs. later LLL velocity, up to the end of the first
      year, with r = 0.53 (R(2) = 0.28) indicating that the early response on lower leg
      growth persists for at least 1 year of GH treatment. CONCLUSIONS: (1) Thirty
      eight percent of the variation in HV during the first year of GH treatment is
      predictable by an initial 8-week period of knemometry. This parallels early
      changes in biochemical markers of bone turnover after GH treatment. (2) There is
      evidence for a baseline variability in HV both in healthy children and in
      children with growth disorders that make growth prediction difficult.

PMID- 12207166
TI  - Iodized oil as a complement to iodized salt in schoolchildren in endemic goiter
      in Romania.
AB  - OBJECTIVE: To evaluate the long-term efficacy and possible side effects of low
      doses of iodized oil on iodine nutrition and thyroid function in endemic goiter
      in Romania. METHODS: Random selection of 214 schoolchildren aged 6-14 years.
      Serial measurements of urinary iodine, thyroid volume with ultrasound, serum
      concentrations of thyrotropin, free thyroxine, thyroglobulin and thyroid
      autoantibodies before and up to 2 years after the oral administration of 200 mg
      iodine in iodized oil. RESULTS: Urinary iodine concentrations indicated a
      moderate iodine deficiency before therapy, sharply increased soon after therapy
      and slowly decreased thereafter but remained within the normal range up to more
      than 1 year after therapy. The prevalence of goiter was 29% before the
      administration of iodized oil and 9% 1 year later. Thyroid function tests and
      autoantibodies were normal before and up to 2 years after therapy. CONCLUSION: A
      single dose of 200 mg iodine from oral Lipiodol appears adequate and safe for
      correcting moderate iodine deficiency in children.

PMID- 12207167
TI  - Normal progression of testicular size in boys with idiopathic short stature and
      isolated growth hormone deficiency treated with growth hormone: experience from
      the KIGS.
AB  - BACKGROUND: The aim of this retrospective analysis was to evaluate the effects of
      growth hormone (GH) treatment on testicular development in boys with idiopathic
      short stature (ISS) and isolated GH deficiency (IGHD) followed in the KIGS
      (Pharmacia International Growth Database). METHODS: For inclusion in the study,
      the patients had to have received more than 1 year of prepubertal GH treatment,
      at least 4 consecutive years of GH treatment in total, and to have attained their
      final height, defined as a height velocity of less than 2 cm/year. Data on 107
      boys in the KIGS database have been analyzed. RESULTS: No significant differences
      in duration of GH treatment and testicular volume at the start of treatment or at
      final height were found between the boys with ISS and those with IGHD. The
      progression of testicular volume in boys with ISS or IGHD during GH treatment did
      not differ from the reference population. CONCLUSIONS: This analysis shows that
      GH treatment does not alter testicular growth in boys with ISS or IGHD. However,
      prospective controlled studies are needed to rule out moderate attenuating or
      stimulating effects.

PMID- 12207168
TI  - In vitro effects of leptin on human adipocyte metabolism.
AB  - OBJECTIVE: Leptin receptors are expressed in adipocytes, suggesting potential
      autocrine/paracrine effects. Studies on the direct effects of leptin on adipose
      tissue metabolism in different species have yielded controversial data. To assess
      the in vitro effects of leptin on human adipocyte metabolism: lipolysis, the
      insulin-induced inhibition of lipolysis and lipogenesis were studied in
      adipocytes obtained from infants and adults. METHODS: Lipolysis was studied by
      incubating adipocytes with increasing concentrations of leptin or isoprenaline.
      Glycerol in the incubation medium was measured as an indicator of lipolysis. For
      the lipogenesis and insulin-induced inhibition of lipolysis experiments, the
      cells were preincubated with 0, 25, or 250 ng/ml of leptin for 2 h. RESULTS:
      Leptin did not stimulate lipolysis in human adipocytes, either in children or
      adults. Preincubation with leptin did not affect the insulin-induced inhibition
      of lipolysis, but decreased the insulin-induced lipogenesis (p < 0.05).
      CONCLUSIONS: This study shows that leptin has no direct lipolytic effect in human
      adipocytes. The lack of effect on the insulin-induced inhibition of lipolysis and
      the negative effect on lipogenesis indicates that the effect of leptin is not at
      the proximal insulin-signalling pathway but further downstream.

PMID- 12207169
TI  - Factors influencing the growth hormone response to growth hormone-releasing
      hormone in children with idiopathic growth hormone deficiency.
AB  - OBJECTIVE: To evaluate the factors influencing the growth hormone (GH) response
      to GH-releasing hormone (GHRH) test in idiopathic GH deficiency. METHODS: 28
      patients aged 4.9 +/- 0.7 years with certain GH deficiency were given GHRH (2
      microg/kg). RESULTS: The GH peak after GHRH was correlated negatively with age at
      evaluation (r = -0.37, p < 0.05) and body mass index (r = -0.44, p = 0.02), and
      positively with anterior pituitary height (r = 0.47, p = 0.02), GH peak after non
      GHRH stimulation (r = 0.78, p < 0.0001) and spontaneous GH peak (r = 0.82, p =
      0.007). It was lower in the patients aged >5 years than in the youngest (p =
      0.04), but it was similar in the patients with and without features suggesting a
      hypothalamic origin. CONCLUSION: The GH response to GHRH test cannot be used to
      differentiate between hypothalamic and pituitary forms of idiopathic GH
      deficiency, probably because the GH response decreases after the first 5 years of
      life, whatever the origin of the deficiency.

PMID- 12207170
TI  - Estrogen receptor-alpha and estrogen receptor-beta are present in the human
      growth plate in childhood and adolescence, in identical distribution.
AB  - OBJECTIVE: To localize estrogen receptor-alpha (ER-alpha) and estrogen receptor
      beta (ER-beta) within the growth plate and adjacent bony tissue of children in
      the prepubertal and pubertal age period. METHODS: Tissue was taken during
      orthopedic surgery (epiphysiodesis) for correction of congenital or traumatic leg
      length difference in 2 prepubertal females and 2 adolescent males.
      Immunohistochemistry was performed on paraffin-embedded or cryostat sections by
      using commercially available rabbit polyclonal antibodies for ER-alpha and ER
      beta. RESULTS: Both ER-alpha and ER-beta were detected within the growth plate in
      all sections investigated. Immunostaining was restricted to hypertrophic
      chondrocytes. In the bony tissue adjacent to the growth plate, osteoblasts
      stained positive for both ER-alpha and ER-beta, whereas osteocytes and
      osteoclasts were negative. Staining with ER-alpha was mainly nuclear but some
      cells also showed cytoplasmic signals, while ER-beta staining was predominantly
      cytoplasmic, only few nuclei stained positive. There was no difference in the
      local distribution of both ERs between tissue from prepubertal and pubertal
      patients. CONCLUSION: Our findings indicate that the hypertrophic chondrocyte is
      the main target cell for estrogen action within the growth plate. The presence of
      ER in prepubertal children suggests that estrogens play a role in skeletal
      maturation under physiological conditions also in this age-group.

PMID- 12207171
TI  - Mitochondrial cytochrome c release precedes transmembrane depolarisation and
      caspase-3 activation during ceramide-induced apoptosis of Jurkat T cells.
AB  - Whilst the role of ceramide, a second messenger of the sphingolipid family, in
      the initiation of receptor-mediated apoptosis is controversial, a growing body of
      evidence is emerging for a role of ceramide in the amplification of apoptosis via
      mitochondrial perturbations that culminate in the activation of execution
      caspases. Treatment of Jurkat T cells with the cell-permeable analog, C(2)
      ceramide, resulted in the rapid onset of apoptosis as evidenced by Annexin V-FITC
      staining of externalised phosphatidylserine residues. Cells bearing this early
      apoptotic marker had a reduced mitochondrial transmembrane potential
      (Delta(Psi)m) that was preceded by the release of cytochrome c from mitochondria.
      Subsequent activation of caspase-3 provides the link between these ceramide
      induced mitochondrial changes and execution caspases that ultimately result in
      the physical destruction of the cell. Collectively these results demonstrate that
      ceramide signalling results in caspase-mediated apoptosis via mitochondrial
      cytochrome c release and are further supportive of the role of ceramide in the
      amplification of apoptosis.

PMID- 12207172
TI  - Mitochondrial permeability transition as a novel principle of hepatorenal
      toxicity in vivo.
AB  - Atractyloside (Atr) binds to the adenine nucleotide translocator (ANT) and
      inhibits ANT-mediated ATP/ADP exchange on the inner mitochondrial membrane. In
      addition, Atr can trigger opening of a non-specific ion channel, within the ANT
      containing permeability transition pore complex (PTPC), which is subject to redox
      regulation and inhibited by cyclosporin A (CsA). Here we show that the cytotoxic
      effects of Atr, both in vivo and in vitro, are determined by its capacity to
      induce PTPC opening and consequent mitochondrial membrane permeabilization (MMP).
      Thus, the Atr-induced MMP and death of cultured liver cells are both inhibited by
      CsA as well as by glutathione (GSH) and enhanced by GSH depletion. Similarly, the
      hepatorenal toxicity of Atr, assessed in vivo, was reduced by treating mice with
      CsA or a diet rich in sulfur amino acids, a regime which enhances mitochondrial
      GSH levels. Atr injection induced MMP in hepatocytes and proximal renal tubular
      cells, and MMP was reduced by either CsA or GSH. Acetaminophen (paracetamol)
      induced acute poisoning was also attenuated by CsA and GSH, both in vitro and in
      vivo. Altogether these data indicate that PTPC-mediated MMP may determine the
      hepatorenal toxicity of xenobiotics in vivo.

PMID- 12207173
TI  - Didemnin B induces apoptosis in proliferating but not resting peripheral blood
      mononuclear cells.
AB  - We have previously shown that didemnin B, a branched cyclic depsipeptide composed
      of seven amino acids and two hydroxy acids, can induce rapid and complete
      apoptosis in HL-60 cells (Grubb, D.R. et al. (1995) Biochem. Biophys. Res.
      Commun. 215, 1130-1136). We now report that didemnin B can induce apoptosis in a
      wide range of transformed cell lines. Resting normal lymphocytes, however, are
      apparently unaffected by exposure to the drug. To investigate whether cell
      transformation, and/or cell proliferation is necessary for didemnin B to induce
      apoptosis, we examined the effect of didemnin B on freshly harvested human
      lymphocytes before and after stimulation with concanavalin A. Didemnin B induced
      apoptosis in normal lymphocytes only after mitogenic stimulation and therefore
      warrants further examination for its potential as a chemotherapeutic agent,
      especially for treatment of leukemia.

PMID- 12207174
TI  - Tumor necrosis factor-related apoptosis inducing ligand (TRAIL) up-regulates
      death receptor 5 (DR5) mediated by NFkappaB activation in epithelial derived cell
      lines.
AB  - Tumor necrosis factor-related apoptosis inducing ligand (TRAIL/APO-2L) activates
      nuclear factor kappaB (NFkappaB). This activation is regulated by the recruitment
      of an adaptor protein Fas associating death domain (FADD) to TRAIL death
      receptors, death receptor 4 (DR4, TRAIL-R1) and death receptor 5 (DR5 TRAIL-R2).
      This leads to recruitment of caspase 8 and receptor interacting protein (RIP) to
      the receptor complex. Upon recruitment of caspase 8 and RIP, NFkappaB inducing
      kinase (NIK) becomes activated causing NFkappaB activation. The role of TRAIL
      induced NFkappaB activation in epithelial cells is unknown. Herein we demonstrate
      that TRAIL increases expression of DR5 in human embryonic kidney (HEK) 293, MCF-7
      and MDA MB 231 epithelial cell lines while DR4 expression remains unchanged.
      Blockage of NFkappaB activation either by expression of dominant negative IkappaB
      or treatment with proteasome inhibitor lactacystin eliminates TRAIL induced DR5
      expression. Expression of FADD dominant negative in HEK 293 cells that prevents
      the recruitment of caspase 8 and RIP to TRAIL death receptors also eliminates
      this increase. By over expression of the p65 subunit of NFkappaB that increases
      NFkappaB transcriptional activity, DR5 expression was increased compared to
      vector alone expressing cells. By blocking TRAIL induced NFkappaB activation, the
      sensitivity of cells to undergo TRAIL induced apoptosis was significantly
      decreased. Conversely, the amount of TRAIL induced apoptosis was increased in HEK
      293 cells over expressing p65 subunit of NFkappaB. Finally blockage of NFkappaB
      activation eliminates the synergistic apoptotic response of TRAIL and etoposide.
      Thus, TRAIL mediated NFkappaB activation increases DR5 expression thereby
      amplifying the apoptotic response of TRAIL in epithelial derived cells.

PMID- 12207175
TI  - Candidate tumour suppressor LUCA-15 can regulate multiple apoptotic pathways.
AB  - Functional screening of a human bone marrow cDNA library for suppressors of CD95
      mediated apoptosis has led to the identification of a 326 bp fragment (Je2),
      which not only suppresses CD95-induced apoptosis in Jurkat T-cells, but maps to
      3p21.3, to an intronic region of the candidate TSG LUCA-15 locus. Here we report
      that overexpression of Je2 in CEM-C7 T-cell line is able to suppress CD95
      mediated apoptosis, and apoptosis induced by TNFalpha and the glucocorticoid
      analogue dexamethasone, but was not able to suppress death induced by the
      topoisomerase II inhibitor etoposide. Je2 inhibition of apoptosis is also
      associated with a change in the pattern of expression of LUCA-15-encoded
      proteins. Je2 might therefore function to inhibit apoptosis by destabilising
      message expression of LUCA-15 and promoting the degradation of its RNA and
      protein. This suppression of apoptosis by Je2 also appears to be associated with
      up-regulation of the apoptosis inhibitory protein Bcl-x(L). This study confirms
      that Je2 is a selective inhibitor of cell death and further implicates LUCA-15
      gene locus in the control of apoptosis.

PMID- 12207176
TI  - The roles of Bid.
AB  - Bid is an abundant pro-apoptotic protein of the Bcl-2 family that is crucial for
      death receptor-mediated apoptosis in many cell systems. Bid action has been
      proposed to involve the mitochondrial re-location of its truncated form, tBid, to
      facilitate the release of apoptogenic proteins like cytochrome c. However, the
      precise mechanism of (t)Bid action is unknown. To advance our knowledge, this
      review evaluates the basic steps of Bid activation--caspase cleavage,
      dissociation of tBid, and lipid-mediated mitochondrial relocation--and their
      structure-function aspects. Relevant current information is thoroughly examined
      to outline the problems that hamper our understanding of the possible roles of
      Bid in cell life and death, and suggest valuable directions for obtaining a
      clarification of its pro-apoptotic mechanism.

PMID- 12207177
TI  - New insights in the role of Bcl-2 Bcl-2 and the endoplasmic reticulum.
AB  - The oncogenic protein Bcl-2 which is expressed in membranes of different
      subcellular organelles protects cells from apoptosis induced by endogenic
      stimuli. Most of the results published so far emphasise the importance of Bcl-2
      at the mitochondria. Several recent observations suggest a role of Bcl-2 at the
      endoplasmic reticulum (ER). Bcl-2 located at the ER was shown to interfere with
      apoptosis induction by Bax, ceramides, ionising radiation, serum withdrawal and c
      myc expression. Although the detailed functions of Bcl-2 at the ER remain
      elusive, several speculative mechanisms may be supposed. For instance, Bcl-2 at
      the ER may regulate calcium fluxes between the ER and the mitochondria. In
      addition, Bcl-2 is able to interact with the endoplasmic protein Bap31 thus
      avoiding caspase activation at the ER. Bcl-2 may also abrogate the function of ER
      located pro-apoptotic Bcl-2 like proteins by heterodimerization. Current data on
      the function of Bcl-2 at the ER, its role for the modulation of calcium fluxes
      and its influence on caspase activation at the ER are reviewed.

PMID- 12207179
TI  - Apoptotic markers for tumor recurrence: a minireview.
AB  - The control of apoptotic mechanisms is integral to many aspects of tumor biology
      and appears to be involved in the process of recurrence. Apoptosis serves as an
      essential mechanism to prevent the proliferation of cells with a higher mutation
      rate, thus tempering malignant transformation. Most antineoplastic therapies
      function by triggering apoptosis in sensitive cells. Resistance to treatment may
      result from specific inhibition of apoptotic signaling. Chemotherapy or radiation
      may increase the mutation rate and hasten tumor evolution in cancer cells that
      are resistant to apoptosis. Summarizing the current evidence regarding the
      usefulness of various apoptotic markers for predicting tumor recurrence, the most
      extensively studied appear to be bcl-2 and p53, as well as the apoptotic rate
      itself, with promising prognostic potential in several neoplasias. Investigative
      results, however, mostly refer to multiple single-center retrospective studies,
      awaiting validation by large prospective clinical trials. Despite initial
      optimism, it becomes apparent that the measurement of one or more gene products
      is inadequate to directly predict a phenomenon as complex as the clinical
      outcome. One of the challenges that is only beginning to be addressed is the
      combined assessment of traditional prognostic parameters and molecular biomarkers
      by creating models or equations to predict the likelihood of recurrence. Such
      screening of patients may help define prognostic categories and influence
      treatment decisions.

PMID- 12207178
TI  - TNF-related apoptosis inducing ligand (TRAIL) and its receptors in tumor
      surveillance and cancer therapy.
AB  - TNF-related apoptosis-inducing ligand (TRAIL/APO-2L) is a typical member of the
      TNF ligand family that induces apoptosis by activating the death receptors TRAIL
      R1 and TRAIL-R2. TRAIL has attracted great attention in recent years as a
      promising anti cancer reagent because recombinant soluble TRAIL derivatives
      induce apoptosis in a broad range of tumor cells but not or only rarely in non
      transformed cells. In this review we will address the putative role of TRAIL in
      cancer treatment in the light of the emerging importance of TRAIL in tumor
      surveillance and discuss the molecular basis of the cooperation of TRAIL and
      chemotherapeutic drugs. In particular, we debate controversial data in the
      literature concerning the cytotoxicity of different TRAIL derivatives on primary
      human cells.

PMID- 12207180
TI  - Multidetector row CT coronary angiography: technique and preliminary experience.
AB  - PURPOSE: To report our preliminary experience with multi-slice spiral CT coronary
      angiography of the coronary arteries. MATERIALS AND METHODS: 50 volunteers (mean
      age 61 years, range 45-72) with baseline heart rates below 70 bpm underwent multi
      detector row CT coronary angiography (GE Light Speed Plus, 140 kVp, 270 mA, 1.25
      mm collimation, 0.5-second rotation time, high quality pitch) with retrospective
      ECG gating after receiving 140-150 ml of iodinated contrast medium (Iopamiro 300
      mg-dl, Bracco, Italy) at a flow rate of 4 ml/sec. Three of the 50 patients had
      previously undergone coronary procedures (1 anterior descending artery stent, 1
      left circumflex artery stent and 1 anterior descending artery percutaneous
      angioplasty) and three were undergoing follow-up examinations after by-pass
      surgery. The remaining 44 patients were asymptomatic and had no history of
      coronary artery disease. All CT angiograms were back-reconstructed from 20 to 80%
      of the diastolic cycle with 10% increments to establish the phase with fewer
      "stair-step" motion artefacts for each artery. Patients with heart rates above 70
      bpm were administered beta-blockers during the five days preceding the
      examination in doses appropriate for the patient's clinical characteristics.
      RESULTS: The CT room occupation time ranged from 25 to 35 minutes (mean time 27')
      and the post-processing time from 30 to 60 minutes (mean time 40'). The left
      anterior descending artery was best visualised in middle diastole (70% of cardiac
      cycle), the circumflex artery at 60% of the cardiac cycle, and the right coronary
      artery at 40%. Out of 132 arteries, 19 (14.4%) were considered non-assessable due
      to "stair-step" motion artefacts, whereas 2 (1.5%) were only partially visualised
      owing to the presence of extensive wall calcifications. Among the 113 assessable
      arteries, we observed: 72 normal coronary arteries without stenosis or wall
      calcifications (54.5%); 28 arteries with minimal wall irregularities and stenoses
      below 50% (21.2%); 7 stenoses >50% involving the right coronary artery (no. 2),
      the anterior descending arteries (no. 4) and the left circumflex artery (no. 1)
      (5.3%). In the remaining 6 patients, optimal visualisation of the stents and
      venous and arterial surgical by-passes was obtained. CONCLUSIONS: Although
      further larger-scale studies are required to compare MSCT coronary angiography
      with CT coronary angiography, the application of MSCT technology to the study of
      the coronary arteries is a promising technique with a good potential for use in
      routine clinical practice. In selected patients (with baseline heart rates <70
      bpm, or after beta-blocker therapy) it is able to provide very interesting
      results and could be used as a method of choice for following patients after
      interventional procedures or as a mass-screening tool to select patients to be
      referred for coronary angiography.

PMID- 12207181
TI  - Multislice CT angiography of the celiac and superior mesenteric arteries:
      comparison with arteriographic findings.
AB  - PURPOSE: The aim of the present study is to evaluate the feasibility of
      multislice computed tomography (MSCT) angiography of the celiac and superior
      mesenteric arteries with a non tailored protocol. Sixteen patients underwent both
      MSCT of the upper abdomen and digital subtraction celiac and superior mesenteric
      angiography. CT examinations included unenhanced scanning and dual-phase
      (arterial and portal) scanning of the upper abdomen. Retrospective 2.5 mm thick
      slices with 50% overlap were used for CT angiography reformations with volume
      rendering (VR), high density maximum intensity projection (HD-MIP) and subvolume
      MIP technique; normal arterial anatomy, variants, stenoses and aneurysms were
      assessed and compared with findings of digital subtraction angiography. RESULTS:
      All VR and HD-MIP reconstructions were considered satisfactory, except in two
      cases because of inappropriate setting of scan parameters; subvolume MIP
      reformations were considered satisfactory in all cases, and superior in the
      depiction of small arteries. Aneurysms and stenoses were always detected, whereas
      a case of replaced right hepatic artery in a patient with complex vascular
      anatomy was misdiagnosed by MSCT angiography. The overall accuracy of VR, HD-MIP
      and MIP CT angiographic reconstructions was 71.9%, 81.8% and 94.6%, respectively.
      CONCLUSIONS: In our preliminary report, CT angiography with multidetector CT has
      proved effective in depicting splanchnic arterial anatomy, and can replace
      diagnostic invasive angiography in most cases. Good quality of axial images is
      necessary for reformations with VR and MIP techniques.

PMID- 12207182
TI  - Intra-articular osteoid osteoma: diagnostic imaging in three cases.
AB  - PURPOSE: To report our experience pertaining to three cases of intra-articular
      osteoid osteoma assessed by means of integrated imaging and review of literature.
      MATERIALS AND METHODS: Medical records, radiologic and nuclear medicine findings
      pertaining to three cases of intra-articular osteoid osteoma were retrospectively
      evaluated and compared with those of surgery. All the patients (2 males, one
      female; age range 8-38 ys) affected by intra-articular osteoid osteoma
      respectively of the elbow, tibio-talar joint and hip were evaluated by means of
      radiographic examination and Magnetic Resonance Imaging (MRI). SE T1-w and T2-w,
      GRE T2*-w, GRE 3D T1-w and STIR pulse sequences were used and axial, coronal and
      sagittal images were acquired. Two patients underwent CT scan. One patient
      underwent skeletal scintigraphy. All the patients underwent surgery. RESULTS: In
      2 out of 3 cases plain radiography allowed the radiologist to suspect the
      presence of the lesion. In the remaining one, plain radiography failed to detect
      both the nidus and the perilesional osteosclerosis; nevertheless, a small
      osteochondral erosion of the humeral condyle suggested the presence of joint
      inflammation, thus leading to further investigation. CT scan well depicted the
      presence of the nidus and, in one case, the presence of joint effusion. MRI was
      always able to detect the nidus, which presented as lesion of low to intermediate
      signal in T1-w images, low signal in the T2-w images in one patient and high
      signal in the remaining two; in these latter STIR images showed high intensity
      nidus and edema of neighbouring cancellous bone. Furthermore, in all patients MRI
      clearly depicted joint effusion. Skeletal scintigraphy demonstrated both the
      lesion and the inflammatory involvement of neighbouring soft tissue. In all
      patients histologic specimen confirmed the diagnosis of osteoid osteoma with
      joint inflammation and synovitis. CONCLUSIONS: According to our results and
      literature data the pre-surgical diagnosis of osteoid osteoma is very difficult
      to achieve. Indeed, only the combination of clinical information and radiologic
      and nuclear medicine findings enables the radiologist to make the right
      diagnosis.

PMID- 12207183
TI  - Renal angiomyolipoma: typical and atypical features.
AB  - Renal angiomyolipoma is an uncommon lesion, well-known to the radiologists as one
      of the few lesions for which a specific diagnosis can be achieved on the basis of
      radiological findings. It contains variable amounts of adipose tissue, smooth
      muscle and vessels. It usually grows as single lesion, and it can be isolated or
      associated with tuberous sclerosis or with the more rare
      lymphangioleiomyomatosis. From a radiological point of view there are typical
      aspects that allow a confident diagnosis, whereas more rarely there are atypical
      aspects that make the diagnosis more controversial. In this review the clinical,
      macro and microscopic morphological aspects of angiomyolipoma are presented as
      well as the therapeutic approaches that can be adopted in different
      circumstances. The most frequent and the atypical characteristics that can be
      appreciated with diagnostic imaging are described as well.

PMID- 12207184
TI  - Magnetic resonance imaging in evaluating functional disorders of female pelvic
      floor.
AB  - PURPOSE: To evaluate the diagnostic capabilities of MRI in the study of
      functional diseases of the female pelvic floor. MATERIALS AND METHODS: Ten
      healthy volunteers and 30 patients with clinically suspected pelvic floor
      deficiency, with or without pelvic organ prolapse, were evaluated by a high field
      strength magnet operating at 1.5 T. In each case SSFSE sequences (TR/TE:25720/67)
      in axial, coronal and sagittal planes, both at rest and during Valsalva's
      manoeuvre, were performed. Based on the MRI findings using fixed and mobile
      anatomical landmarks, the functional disease of the pelvic floor was diagnosed
      and quantified based on the identification and grading of visceral prolapse. The
      MRI findings were compared with the clinical findings in all cases and with the
      surgical data in the 7 patients who had undergone surgery. RESULTS: The MR image
      quality was adequate in all cases. In the group of symptomatic women MRI
      diagnosed: urethral hypermobility syndrome: 22 cases; isolated abnormalities of
      the anterior compartment: 8 cases of cystocele (low grade: 2, middle grade: 2,
      severe: 4); isolated abnormalities of the middle compartment: 6 cases of
      hysterocele (low grade: 2, middle grade: 4); isolated abnormalities of the
      posterior compartment: 5 cases of low-grade rectocele; 2 cases of enterocele (1
      low grade, 1 middle grade); multi-compartment abnormalities: 11 cases; joint
      prolapse of anterior and middle compartment: 5 cases; joint prolapse of posterior
      and middle compartment: 3 cases; joint prolapse of anterior, middle and posterior
      compartment: 3 cases. The values of both fixed and mobile landmarks were
      significantly higher in the symptomatic group compared with the healthy
      volunteers. MRI confirmed the pelvic examination findings in all cases; in
      particular MRI findings were in total agreement with the clinical severity of
      prolapse, as defined by the Baden-Walker classification. In 7 cases MRI detected
      additional alterations (4 cases of hysterocele and 3 of enterocele) that had been
      missed at clinical evaluation. DISCUSSION AND CONCLUSIONS: In our experience MRI
      made an important contribution to the diagnosis and grading of functional
      disorders of the female pelvic floor and pelvic organ prolapse. The ability to
      simultaneously demonstrate both muscular and ligamentous structures and pelvic
      viscera, without using X-rays or contrast agents, is the main reason for the good
      results achieved by MRI and for its widespread use in this disorder. Furthermore
      the use of fast, breath-hold sequences can provide high-quality images both at
      rest and during Valsalva's manoeuvre. In conclusion MRI proved to be an accurate
      imaging tool that is more sensitive than clinical pelvic evaluation in diagnosing
      and grading functional disorders of the female pelvic floor and pelvic visceral
      prolapse.

PMID- 12207185
TI  - Multidetector CT-urography in the study of urological complications in renal
      transplant.
AB  - PURPOSE: To evaluate the value of CT-urography in the diagnosis and follow-up of
      the urological complications of renal transplantation. MATERIALS AND METHODS: We
      performed 19 CT-urography examinations (3 of which were follow-up) on 15 patients
      by using a spiral multislice CT scanner and multiplanar reconstructions. The
      examinations were carried out directly after administration of 100 ml of
      iodinated contrast medium by slow iv infusion, with acquisitions starting 5
      minutes after the end of the infusion. Surgery was regarded as the gold standard
      for the diagnosis of urological complications in the operated patients, whereas
      in patients who had undergone medical therapy or stent placement the gold
      standard was 1 month ultrasound and clinical follow-up with evaluation of
      diuresis and renal function. RESULTS: Between January 1999 and December 2001 a
      total of 210 kidney transplantations were performed at our hospital. There were
      34 urological complications in 28 patients with a 16.1% prevalence, consistent
      with the major international studies. The complications detected were 14 urine
      leaks and 19 ureteral obstructions secondary to stones, oedema, blood clots and
      stricture. We observed one case of reflux in the allograft ureter. Fourteen out
      of 16 CT-urography examinations yielded important clues for the diagnosis of
      urological complications in kidney allografts, completely replacing standard
      urography. In particular, CT-urography correctly detected 5 urinary fistulas by
      demonstrating iodinated contrast material leaks along the ureteral tract, and 8
      cases of obstructive uropathy due to different causes (1 submucosal tunnel edema,
      1 blood clot, 1 stone and 5 cases of ureteral stricture). One case of urinary
      fistula and one of obstructive uropathy were not detected. DISCUSSION AND
      CONCLUSIONS: CT-urography proved to be an important diagnostic tool in the
      evaluation of urological complications of kidney allografts, showing a diagnostic
      accuracy over 90%; it is useful for confirming the type and site of urological
      lesions, and therefore to provide guidance for a targeted surgical approach.
      Compared with excretory urography, which is no longer used in this diagnostic
      field, CT-urography is more complete and precise as it provides information not
      only about the urinary tract, but also about the kidney parenchyma and pararenal
      fluid collections. The only disadvantage, which limits its use to selected cases,
      is the risk associated with the use of iodinated contrast agents in patients with
      impaired renal function.

PMID- 12207186
TI  - Regarding six cases of mesenteric panniculitis: US, spiral CT, Magnetic
      Resonance.
AB  - PURPOSE: Mesenteric panniculitis is a rare inflammatory disease. The inflammation
      produces a lesion which appears as a mass, and normally produces abdominal pain
      without any other significant clinical signs. The radiological pattern is not
      typical, but the diagnosis is aided by a number of elements which are important
      to recognise in order to avoid invasive diagnostic methods or therapy. Six cases
      are presented, all evaluated with sonography, Color-Doppler US, Spiral CT and
      Magnetic Resonance Imaging (MRI). MATERIALS AND METHODS: We evaluated six
      patients with negative clinical histories and endoscopic examinations. The
      patients reported the recent onset of indefinite symptoms and abdominal pain
      treated at home. Abdominal plain film radiography, performed also in the upright
      position, was negative in all cases. All the patients underwent abdominal
      sonography and Colour-Doppler ultrasound. Spiral CT scanning was carried out with
      5-mm slice thickness, a pitch of 1.3, and single breath-hold volumetric
      acquisitions starting 60 s after intravenous injection of iodinated contrast
      medium. Only in one case, where Crohn's disease was suspected and subsequently
      not confirmed, did we perform small bowel enema with transparent contrast medium
      to distend the bowel loops. MR imaging was performed using a medium-field 0.5 T
      magnet, T1-weighted Fast SE, T2-weighted Fast SE and Fast STIR sequences. We
      considered: the mass effect of the lesion; the presence of vascular infiltration;
      the presence of a peripheral pseudocapsule; the presence of perivascular loose
      tissue proper, having densitometric characteristics distinctive from the
      remaining fatty tissue of the diseased mesentery. RESULTS: In all cases
      ultrasound detected only an central abdominal mass. The fatty content of the
      mass, however, reduced US transmission, preventing the acquisition of more
      complete information. The color-Doppler US also produced little data, except some
      isolated colour spots within the mass. In no case did CT directly detect a
      peripheral pseudocapsule, although it did identify a difference in density
      between the perivisceral abdominal loose tissue and the mesentery proper, which
      is hyperdense. The vessels inside the mesentery on no occasion appeared
      infiltrated. The CT scans were unable to identify differential elements between
      the perivascular loose tissue and the fatty tissue of the main mass. MRI, on the
      other hand, enabled the detection of the peripheral pseudocapsule which
      surrounded the mesenteric mass as a band of tissue with low signal intensity in
      all the sequences performed. In fast STIR sequences suppression of the fat signal
      of the mesenteric mass was insufficient, being suppressed only in the adipose
      tissue surrounding the arterial branches of the mesenteric artery. Four of the
      six patients underwent exploratory laparotomy. The histological examination of
      the biopsies revealed a massive inflammatory infiltration of the mesentery, with
      relatively little involvement of the perivascular adipose tissue. CONCLUSIONS: In
      mesenteric panniculitis, sonography and spiral-CT are useful in focusing
      diagnostic attention on the mesentery, but only MRI is capable of providing the
      information necessary formulating a complete diagnosis of the disease.

PMID- 12207187
TI  - New automatic software for virtual colonoscopy: technical aspects.
AB  - PURPOSE: To evaluate a new virtual endoscopy software package capable of
      automatically plotting the path along which to perform endoscopic exploration.
      MATERIALS AND METHODS: We reviewed the examinations of 50 patients with colonic
      neoplasms studied by CT colonoscopy by using a single-detector CT scanner
      (Philips Tomoscan AVE1). The technical parameters used were: slice thickness 3
      mm, pitch 1.4, reconstruction interval 2-2.5, 120 kV, 150-200 mA. The images were
      processed on a separate workstation (Philips Easy Vision 5.1) running an
      experimental virtual endoscopy software package capable of automatically drawing
      a line along which to move the virtual endoscope to explore the colon.
      Reconstruction of the endoscopic images along the path obtained was set at an
      interval of 15-20 mm between one endoscopic view and the next, to a total of 70
      to 120 images. The endoscopic animated image sequence was then saved and
      evaluated by comparing the starting axial images and the three-dimensional images
      obtained. RESULTS: The programme plotted the endoscopic path correctly in a
      single pass in 40 of the 50 cases studied. The overall time spent by the
      radiologist on image-processing did not exceed 5 minutes. DISCUSSION: The need to
      reduce the time spent by audiologists on post-processing has led to a gradual
      improvement in image-processing hardware and software. In the context of virtual
      endoscopy, one of the main goals is to obtain the path for endoscopic exploration
      in as short a time as possible. The programme we evaluated successfully fulfils
      this requirement as, once the image-processing technical parameters have been
      defined, it plots a path along the entire colon and performs the reconstruction
      procedures automatically. The time spent by the operator on post-processing does
      not exceed 5 minutes. CONCLUSIONS: The new programme evaluated in this study
      facilitates the processing of endoscopic images, reduces radiologist time and may
      contribute to the widespread use of virtual colonoscopy.

PMID- 12207188
TI  - Magnetic Resonance applications in dental implantology: technical notes and
      preliminary results.
AB  - PURPOSE: To evaluate the possible use of Magnetic Resonance Imaging (MRI) in the
      field of dental implantology, for identifying the mandibular nerve, as proposed
      by several authors. MATERIALS AND METHODS: MRI was used for the study of the
      mandible in ten subjects (five healthy volunteers and five subjects awaiting
      dental implants). Imaging was performed on a 1.0-T MR scanner with a brain coil.
      T2 TSE, T1 spin-echo and T2 gradient-echo sequences were performed, both parallel
      and perpendicular to the horizontal portion of the mandible, with a thickness of
      3 mm. RESULTS: In all the subjects MRI clearly identified the intraosseous course
      of the inferior alveolar neurovascular bundle within the mandibular canal.
      CONCLUSIONS: MRI appears useful for the depiction of the mandibular canal before
      dental implantation. Further studies are required to compare the accuracy of MRI
      and CT based on a statistically significant sample.

PMID- 12207189
TI  - Osteo-articular, mammographic and thoracic films: clinical evaluation of digital
      view box versus conventional view box.
AB  - PURPOSE: To compare in a clinical setting a conventional view box with a digital
      view box (Smart Light 2000 Digital Film Viewer System, Smart Light, Israel) in
      the identification of osteo-articular, mammographic and thoracic lesions.
      MATERIALS AND METHODS: Six radiologists (two for each imaging procedure), experts
      in osteo-articular, mammographic and thoracic diseases, independently, compared
      600 plain films (100 patient with two projections for each imaging procedure).
      The radiologists evaluated the films by filling-out a multiple choice
      questionnaire containing questions concerning the type of pathology seen and the
      technical quality of the radiography in terms of exposure along with specific
      questions concerning each of the imaging procedures. RESULTS: We observed a
      higher sensitivity of the digital view box for lesion identification (p<0.05);
      furthermore, we analyzed a greater number of radiographs, recovering technically
      unsuitable films, because of over or under-exposure (high or low optical
      density). The interreader agreement was also good (> 0.75). The better lesion
      perception derived from the increase luminance of the digital view box in the
      evaluation of higher film densities, such as in overexposed films. DISCUSSION.
      The technical characteristics of the digital view box reduce or eliminate
      negative factors that reduce perceptional performance, and often permit the
      recovery of films that would have otherwise been considered technically
      unreadable.

PMID- 12207190
TI  - Philloides tumor of the breast detected by US in a 11 years old patients. A case
      report.

PMID- 12207191
TI  - Unusual pelvic mass in female newborn: mucocolpos by imperforate hymen.

PMID- 12207192
TI  - Double blind ureteral duplication: report of an unusual case.

PMID- 12207193
TI  - Urethral duplication associated with penile abnormalities.

PMID- 12207194
TI  - Primary heart angiosarcoma with pulmonary metastases.

PMID- 12207196
TI  - [The biological effects of a nuclear explosion. Introduction of a new system on a
      colorimetric scale (black, grey, red, orange, yellow and white zone) to estimate
      the effects of fall-out on civilian populations].
AB  - Following September 11 the eventuality of terrorist attacks using bags containing
      nuclear devices is considered possible in western cities like New York, London,
      Paris, Rome, Berlin, Moscow etc. However, with a modern Civil Defence programme
      the effects of a catastrophe of this nature can be partially limited, at least as
      far as Fall-out is concerned. The present paper explains the medical reasons for
      building anti-fall-out shelters for the larger part of western populations: from
      the USA to Russia. The paper also sets out a new method for classifying levels of
      radioactive Fall-out based on a scale of colours (black, grey, red, orange,
      yellow and white) whatever kind of radioactivity is involved (total gamma levels,
      Cesium 137 levels, Strontium 90 levels). The arrival times for fall-out in each
      area of the scale are fixed, whatever the energy of the explosion and the speed
      of the wind might be. The radioactive decay in each area of the scale, from the
      time of arrival of the fall-out is described with precision. Also described are
      the acute radiation syndrome, tumours, miscarriages and genetic diseases. A
      nomogram is attached for civil defence purposes showing the leeward extension of
      these areas, easily measurable in just a few minutes, if four parameters are
      known: ground zero (locality) of the explosion, the energy of the explosion, the
      direction of the wind and the speed of the wind.

PMID- 12207195
TI  - Bilateral renal embolization in the treatment of patients with renal
      insufficiency and arterial hypertension: report of a case of polycystic kidneys.

PMID- 12207197
TI  - [Cardiovascular prevention: new biochemical plasmatic markers of risk].
AB  - The primary prevention of acute coronary syndromes is an open question. The
      scientific progress has discovered new biochemical markers of cardiovascular
      disease risk that may be useful for primary prevention. They are plasmatic
      markers of inflammation (serum amyloid A, C-reactive protein, phospholipase A2)
      and of infection (seropositivity to Chlamydia pneumoniae, cytomegalovirus). They
      are plasmatic markers of endothelial activation (adhesion molecules such as ICAM
      1, VCAM-1) immunological markers (autoantibodies against oxydized LDL, hemostatic
      markers (TFPI, PAI-1) and metabolic indices (Lpa, homocystein). A gap is evident
      between the scientific progress in the knowledge of the epidemiology of
      cardiovascular pathology and its application in clinical practice. The priority
      should become the population approach to primary prevention: the rapidly changing
      and complex global context presents new challenges for public health
      practitioners struggling to implement preventive policies and programmes. New
      risk factors of cardiovascular disease have been pointed out by research. This
      study shows the situation on the topic with critique and updated analysis.

PMID- 12207198
TI  - [Obligatory and facultative symptoms of the Alice in wonderland syndrome].
AB  - The Alice in Wonderland syndrome (AIWS), as described by Todd in 1955, denotes a
      variety of self-experienced paroxysmal body schema disturbances (obligatory core
      symptoms of the AIWS) which may co-occur with depersonalization, derealization,
      visual illusions and disorders of the time perception (facultative symptoms of
      the AIWS). The name comes, of course, from Lewis Carroll's 1865 novel "Alice's
      Adventures in Wonderland", which is believed to have been inspired by Carroll's
      own migraine experiences documented as early as 1856. Recent studies of the AIWS
      occurring as somesthetic migraine aura indicated that the body schema disturbance
      of macrosomatognosia most frequently affects the head and upper extremities,
      paralleling the extension of their representation in the human brain. As a
      misapprehension commonly encountered in the medical literature, it has been
      suggested to define the AIWS by the presence of visual rather than somesthetic
      perceptual disturbances, e.g. metamorphopsia and/or visual hallucinations, but
      this change and broadening of Todd's definition of the AIWS turns it to a both
      scientifically and clinically useless concept.

PMID- 12207199
TI  - [Vomiting].
AB  - Vomiting, the culminating sign of nausea, is primarily a protective reflex
      occurring in a wide variety of vertebrates. Even tough nausea and vomiting are
      among the most basic neural reflexes, they remain poorly understood. Poorly
      understood are the pathogenetic mechanisms from the anatomic receptor and
      neuroendocrine point of view. This is the reason why drugs are useful in some
      types of vomiting but not in others. The aim of this paper is to summarize
      current knowledge about anatomy of vomiting reflex, neurotransmitter receptor
      subtypes, agonists and antagonists of serotonin and substance P. Particularly in
      the treatment of post-chemotherapy and postoperative vomiting. It is pointed out
      that nausea an vomiting may be field of neurochemical and neuropharmacological
      research. Finally, in clinical research drugs for vomiting therapy may be useful
      in other pathologies (migraine, rheumatoid arthritis, bronchial asthma).

PMID- 12207200
TI  - Efficacy of anthracyclines and paclitaxel as first line chemotherapy in patients
      with visceral metastases of breast cancer.
AB  - BACKGROUND: Anthracyclines combined with paclitaxel are one of the most active
      schedules in patients with advanced breast cancer: response rates range from 40
      to 80%, considering all metastatic sites (visceral and soft tissues). We
      performed a non-randomized phase II trial with anthracyclines/paclitaxel
      combination to evaluate response and toxicity only in patients with visceral
      metastases. METHODS: Twenty-seven patients (median age 50 years; range 30-72)
      with visceral metastases of breast cancer were enrolled in this study. Overall,
      11 patients had lung metastases (41%), 10 liver (37%), 4 liver-lung metastases
      (15%) and 2 peritoneal carcinosis (7%). 7 patients had received adjuvant
      anthracycline-based chemotherapy (26%) and 10 patients adjuvant CMF combination
      chemotherapy (37%); 10 patients (37%) received hormonal therapy for advanced
      disease. Treatment schedules were: group A) 17 patients, Adriamicyn 50 mg/m2 on
      day 1 i.v. bolus and Paclitaxel 175 mg/m2 on day 2 i.v. 3 hours infusion, every 3
      weeks; group B) 10 patients, epirubicin 90 mg/m2 on day 1 i.v. bolus and
      paclitaxel 200 mg/m2 on day 2 i.v., 3 hours infusion, every 3 weeks. The number
      of cycles administered was 141 with a median of 5 (range 3-9). RESULTS: All
      patients were evaluable for response and toxicity. The objective response rate
      was 59% - 16 patients - (15% complete and 44% partial remission), 95% C.I. 40.7
      77%; 10/17 in group A and 7/10 in group B. Stable disease 30% (8 patients) and
      progressive disease 11% (3 patients). The median duration of response was 5
      months (range 1-16); median time to progression 13 months (range 3-18) and median
      survival 17 months (range 4-24). The main toxicity was neutropenia, occurred in
      16 patients (59%; grade IV in 7 patients, of whom 2 febrile neutropenia, and
      grade III in 9 patients); grade III gastrointestinal toxicity in 2 patients;
      grade III neurological toxicity in 1 patient; grade III stomatitis in 2 patients.
      No congestive hearth failure or treatment death related was observed.
      CONCLUSIONS: These schedules of anthracyclines and paclitaxel confirmed their
      efficacy in metastatic breast cancer even in patients with visceral disease.
      Neutropenia was the main toxicity; grade IV neutropenia was more frequently
      observed in epirubicin/paclitaxel arm.

PMID- 12207201
TI  - Protein S deficiency. Description of a case associated with chronic inflammatory
      bowel disease.
AB  - Thrombotic disease is one of the most relevant clinical problems for morbility
      and mortality. We can differentiate congenital and acquired forms. In this short
      communication we describe 1 case observed by us that seems interesting for the
      association of a congenital and acquired form [Protein S deficiency and
      inflammatory bowel disease (IBD)] and for the dramatic events suffered before
      receiving a complete diagnosis and therapy, indicating the importance of
      recollection of information from the patients, starting from anamnestic data.

PMID- 12207202
TI  - [Long term study on the efficacy and safety of lornoxicam in rheumatoid
      arthritis].
AB  - BACKGROUND: To assess the long term safety and therapeutic action of lornoxicam,
      a new non steroidal anti-inflammatory agent, in rheumatoid arthritis. METHODS:
      Open trial was carried out on different dosage schedules of lornoxicam (4 or 8 mg
      bid and 4mg tid) administered for six to twelve months. Patients of both sexes
      were enrolled, with classical or definite rheumatoid arthritis according to the
      A.R.A. criteria. RESULTS: Thirty-four patients (28 F, 6 M) were admitted, mean
      age (+/- SD) 53.9+/-14.2 years, mean duration of illness 9.2+/-10.7 years.
      Lornoxicam 8-16 mg/day showed good safety and therapeutic activity in long term
      treatment. Clinical improvement was limited, but progression of the disease was
      controlled. No adverse events were complained. CONCLUSIONS: Lornoxicam presented
      a worth-while therapeutic action and a good tolerability in rheumatoid arthritis
      long term treatment.

PMID- 12207203
TI  - [TOWARDS A MORE LATINAMERICAN ACCENT JOURNAL: CHALLENGE FOR THE NEXT MILLENIUM]

PMID- 12207204
TI  - [HELICOBACTER PYLORI INFECTION ERRADICATION IN DISPEPTIC PATIENTS WITH AND
      WITHOUT PEPTIC ULCER]
AB  - BACKGROUND: Helicobacter pylori (HP) infection is very prevalent worldwide, and
      has been associated with the presence of duodenal ulcer, gastric ulcer and
      chronic active gastritis. It is also speculated that HP may have a role in
      gastric cancer development. Triple drug schemes have been shown to be the most
      effective approach to erradicate HP infection. Nevetheless, high rates of
      resistance against some antibiotics as well as high costs affect the
      effectiveness of these therapies. The goal of the present study is to assess the
      effectiveness of the combination of tetracycline, furazolidone and bismuth in
      erradicating HP, as well as the changes in the histology.METHODS: Patients with
      diagnosis of HP infection, found in their antral gastric biopsies (hematoxylin
      and eosin staining (H-E)), were included. They received the following scheme for
      10 days: tetracycline 500 mg qid., furazolidone 100 mg qid., and colloidal
      bismuth subcitrate 120 mg qid. Patients were instructed to come back for follow
      up 6 to 8 weeks after starting the therapy. At that time a control upper
      endoscopy was performed and 3 antral biopsies were taken. Biopsies were stained
      with H-E and read by experienced pathologists. In both, the biopsy before
      treatment and the control biopsy, the following parameters were looked for:
      presence and density of HP; presence, depth and grade of chronic gastritis
      (lymphoplasmocytic infiltrate); presence and grade of inflammatory activity
      (polymorphonuclear inflitrate); presence of glandular atrophy; presence, grade
      (partial or total) and extent (focal or multifocal) of mucinous damage
      (epithelial damage); presence of intestinal metaplasia; and presence of lymphoid
      follicles.RESULTS: Fifty-nine patients (30 men and 29 women) completed per
      protocol. Mean age was 43 +/- 18 (range: 14-73). HP erradication was achieved in
      54 patients (91.5%). Control biopsies showed improvement in the following
      parameters: presence and density of HP (p<0.001); presence, depth and grade of
      chronic gastritis (p<0.001); presence and grade of inflammatory activity
      (p<0.001); presence, grade and extent of mucinous damage (p<0.001); and presence
      of lymphoid follicles (p<0.001). Neither the presence of glandular atrophy nor
      the presence of intestinal metaplasia showed any significant change. Patients who
      did not erradicate HP showed no significant difference in any of the
      parameters.CONCLUSIONS: The triple drug scheme including tetracycline,
      furazolidone and bismuth is effective in HP erradication. Erradication of HP is
      followed by an improvement in the following histologic parameters: presence,
      depth and grade of chronic gastritis (LMN infiltrate); presence and grade of
      inflammatory activity (PMN infiltrate); presence, grade and extent of mucinous
      damage; and presence of lymphoid follicles. This scheme is a cost-effective
      alternative for the therapy of HP infection in low income populations with a high
      prevalence of infection with this bacteria.

PMID- 12207205
TI  - [HELICOBACTER PYLORI, CHRONIC GASTRITIS, GASTRIC ANDDUODENAL ULCER: STUDY OF 1638
      PATIENTS]
AB  - We anaylize in patients from high socio economic level the histologic findings of
      biopsies from the gastric mucosa taken endoscopically. Patients with upper
      gastrointestinal symptoms were examined with esophagogastroduodenoscopy. In the
      histologic study we considered: presence of Helicobacter pylori, mucinous damage,
      displasia, atrophy and intestinal metaplasia. Patients were divided in two
      groups: those who endoscocopically did not present gastric or duodenal active
      ulcer, gastric neoplasia or were not gastrectomized or vagotomized and those in
      which active gastric or duodenal ulcer was found. The first group was comprised
      of 1406 patients (647 women and 769 men). 57.33% (806) showed presence of
      Helicobacter pylori in the histologic study. Males presented higher prevalence of
      the bacteria (57.32% vs 42.68%, p=0.021873). Atrophys was found in 8.25% and was
      more frequent in patients with H. pylori (78.45% vs 21.55% p=0.0000026) /
      Intestinal metaplasla was found in 11.24% being related more with the presence of
      H.pylori (74.68% vs 25.32%, p=0.0000043). In the second group comprised of 232
      patients: 192 males (82.7%) 82.75% showed presence of the bacteria. There was not
      a statistical difference by comparing sex and age vs presence of ulcer.

PMID- 12207206
TI  - [IT IS USEFULL THE UREA/CREATININE RATE FORDIFFERENTIATION OF UPPER FROM LOWER
      GASTROINTESTINAL BLEEDING?]
AB  - Gastrointestinal bleeding constitutes a third part of the hospitalizations in our
      service. Some times is difficult to clinically distinguish the site of bleeding.
      It was pointed that the urea/creatinine ratio can help to define the site of
      bleeding, but there is a lot of superposition in the results. We studied
      prospectively 154 patients with gastrointestinal bleeding. 123 (79.9%) patients
      had upper gastrointestinal bleeding with an urea/creatinine ratio of 62.27 +/-
      29.13 and 31(20.1%) patients had lower gastrointestinal bleeding with an
      urea/creatinine ratio of 39.49 +/- 13.83. This difference is statistically
      significant but has a lot of overlap results. Defining gastrointestinal bleeding
      as an urea/creatinine ratio greater than 60, we found a great specificity
      (96.77%) but a low sensibility (51.22). In addition, when we only took
      hematochezia cases, that usually is a diagnostic problem, the specificity was
      96.42% and the sensitivity 46.15%. In conclusion, an urea/creatinine ratio
      greater than 60 usually indicate us an upper gastrointestinal bleeding, but
      values below of 60 isn't of diagnostic value.

PMID- 12207207
TI  - [CONTRIBUTION STUDY TO THE EPIDEMIOLOGY OF HELICOBACTERPYLORI IN PERU: ANALYSIS
      OF 3005 CASES]
AB  - Compiling our observations from the last 15 years in regard to the epidemiology
      of Helicobacter pylori in Peru, we have analized 3005 cases. Studying and
      comparing the rates of infection among japanese inmigrants living in Peru for
      more than 10 years, niseis, japanese visitors and peruvians, we found similar
      rates. According to these results it seems that at least in japaneses there is
      not any genetic predisposition to acquire the infection. Studying peruvians of
      different socioeconomic levels, we observed similar rates of infection with the
      exception of women of high socioeconomic level. It seems that the last group of
      people is not exposed to the different mechanisms of infection. We found similar
      rates of infection in patients of low socioeconomic level living in the coast,
      sierra and jungle. Our studies in children showed that the infection is acquired
      during early childhood. Therefore in Peru we have not observed an ascending rate
      of infection according to age as has been described in industrialized countries.
      Analizing water from 48 sources we found Helicobacter pylori in 24 samples, 20 of
      them were taken from the municipal source of water. Water seems to be an
      important vehicle of infection, according to our studies, in children drinking
      water from different sources.

PMID- 12207208
TI  - [TREATMENT OF HUMAN HEPATIC FASCIOLASIS WITH TRICLABENDAZOLE]
AB  - This study has the purpose to evaluate the effect of triclabendazole over human
      fasciolasis produced by Fasciola hepatica. 70 patients with positive stools
      studies for fasciolasis were treated with 12 mg/kg/ day of triclabendazole for 2
      days.The control stools tests were performed 15 and 45 days after the treatment
      was finished. Parasitologic negativitation of stools was found in 83% of those
      patients who recieved 1 cycle of treatment. 14% needed 2 cycles and 3% a third
      one.No important side effects were reported because of treatment. We conclude
      that triclabendazole is highly efficient and good against liver fasciolasis in
      humans.

PMID- 12207209
TI  - [TREATMENT OF CHOLESTASIS]
AB  - Cholestasis includes a wide variety of causes. When extrahepatic causes are
      excluded a number of disorders causing intrahepatic cholestasis are defined at
      this time. The cellular mechanisms of cholestasis have as yet to be completely
      understood. Diagnosis can be made using history, physical examination, a few
      laboratory parameters, serology and also ERCP. Treatment depends largely on the
      cause of the cholestasis. Regarding the leading disorders such as PBC and PSB,
      ursodesoxycholic acid and in some instances in addition immunosuppressants are
      thus far established. Liver transplantation remains an important treatment
      option. All other treatments need to be evaluated against these standard
      measures.

PMID- 12207210
TI  - [PRIMARY SCLEROSING CHOLANGITIS ASSOCIATED TO ULCERATIVECOLITIS AS A CAUSE OF
      CIRRHOSIS]
AB  - We report case of a peruvian patient with cirrhosis due to primary sclerosing
      cholangitis, associated with ulcerative colitis. The patient presented initially
      with intermittent diarrhea, manifesting features of chronic liver failure which
      progressed rapidly.Primary sclerosing cholangitis is a progressive diasease
      affecting intra and extrahepatic billary radicles, and is associated with
      ulcerative colitis in the majority of cases. The diagnosis is made by
      cholangiography, showing areas of stenosis, irregularity and dilatation of the
      biliary tree.In this article we report the clinical presentation and course of
      the patient, reviewing recent literature with emphasis in the association between
      primary sclerosing cholangitis and ulcerative colitis.

PMID- 12207211
TI  - The calculative nature of microbial biofilms and bioaggregates.
AB  - Biological proliferation is optimized at various levels of organization,
      including the molecule (e.g. nucleic acids, prions), the cell (e.g. prokaryotic
      cells, eukaryotic cells), and the community (e.g. microbial biofilms,
      bioaggregates). Although it was initially assumed that this occurred through the
      genesis of information within DNA alone, it now appears that innovative design
      originates at other levels of organization in addition to DNA. For example, the
      recombination of community structures affects the proliferation rate of genetic
      structures; and the recombination of genetic structures affects the proliferation
      rate of community structures. This feedback mechanism computes compromises
      between the form and function of both community and nucleic acid. A nested series
      of proliferating objects (e.g. genetic structure, cell structure, community
      structure) is thus capable of continually updating the form of each object in the
      series. This accounts for the calculative nature of prokaryotic cells, eukaryotic
      cells, biofilms, bioaggregates, microbial consortia, and most other complex
      adaptive systems.

PMID- 12207212
TI  - Low prevalence of vancomycin-resistant enterococci in clinical samples from
      hospitalized patients of the Canary Islands, Spain.
AB  - Over the last decade vancomycin-resistant enterococci (VRE) have emerged as
      nosocomial pathogens. The aim of this study was to determine the prevalence of
      VRE in clinical samples from hospitalized patients in the Canary Islands. From
      April to November 2000, 437 enterococci were isolated from patients hospitalized
      at the four main health care centers in those islands. Identification to the
      species level was performed with the GPS-TA (Vitek 1) or the Wider I system. A
      PCR assay was used to determine the genotype of glycopeptide resistance ( vanA,
      vanB, vanC1, and vanC2/C3 genes). Only three (0.7%) VRE were detected: one vanA
      Enterococcus faecalis, and two vanC1 Enterococcus gallinarum. To our knowledge,
      this is the first VRE study carried out in the Canary Islands hospitals, and the
      results showed a low prevalence of VRE.

PMID- 12207213
TI  - Effect of the fungicide Prochloraz-Mn on the cell wall structure of Verticillium
      fungicola.
AB  - The chemical structure of the cell wall of two isolates of Verticillium
      fungicolacollected from diseased fruit bodies of the commercial mushroom Agaricus
      bisporus treated with the fungicide Prochloraz-Mn was analyzed. The isolates were
      obtained during different periods of time and grown in the absence and presence
      of the LD(50) values of the fungicide for V. fungicola. In addition, another V.
      fungicola isolate collected previous to the routine utilization of Prochloraz-Mn
      but grown under the same conditions was also analyzed. The overall chemical
      composition of the cell wall from the three isolates showed detectable
      differences in their basic components, with a significant decrease in the protein
      content in fungicide-treated cells. This inhibitory effect was partially
      compensated by an increase in neutral and/or aminated carbohydrates and was
      accompanied by appreciable modifications of polysaccharide structure, as deduced
      after methylation analysis and gas-liquid chromatography-mass spectrometry (GLC
      MS). Moreover, differences in hyphal morphology caused by the fungicide were
      observed by transmission electron microscopy (TEM).

PMID- 12207214
TI  - beta-Galactosidase activity of Escherichia coli under long-term starvation,
      alterations in temperature, and different nutrient conditions in lake water.
AB  - beta-Galactosidase activity of Escherichia coli was investigated in response to
      long-term starvation, changes in temperature and the presence of certain nutrient
      sources in lake water. beta-Galactosidase activity decreased markedly in filtered
      autoclaved lake water at 25 degrees C and 37 degrees C, whereas it remained
      almost constant at 4 degrees C and 15 degrees C for 60 days. Increases in beta
      galactosidase activity were observed in response to the following nutrient
      sources: glycine, serine, methionine and ammonium sulfate at 4 degrees C; glycine
      and ammonium sulfate at 15 degrees C; glycine, serine, methionine and ammonium
      sulfate at 30 degrees C. Glycine addition led to an increase in beta
      galactosidase activity of almost five and seven orders of magnitude at 15 degrees
      C and 30 degrees C, respectively. In addition, L-methionine had the strongest
      influence on beta-galactosidase activity, which was detected as an increase of
      seven and eleven orders of magnitude at 4 degrees C and 30 degrees C,
      respectively. The effect of several amino acids and other nitrogen sources
      depended on the concentration of the nutrient source and the temperature. The
      results showed that, in lake water, long-term starvation, temperature change, and
      variations in nitrogen sources alter beta-galactosidase activity. Those effects
      should be taken into account when monitoring coliforms from the environment.

PMID- 12207215
TI  - Sulfide fluxes in a microbial mat from the Ebro Delta, Spain.
AB  - The sulfur cycle of Ebro Delta microbial mats was studied in order to determine
      sulfide production and sulfide consumption. Vertical distribution of two major
      functional groups involved in the sulfur cycle, anoxygenic phototrophic bacteria
      and dissimilatory sulfate-reducing bacteria (SRB), was also studied. The former
      reached up to 2.2x10(8) cfu cm(-3) sediment in the purple layer, and the latter
      reached about 1.8x10(5) SRB cm(-3) sediment in the black layer. From the changes
      in sulfide concentrations under light-dark cycles it can be inferred that the
      rate of H(2)S production was 6.2 micro mol H(2)S cm(-3) day(-1) at 2.6 mm, and
      7.6 micro mol H(2)S cm(-3) day(-1) at 6 mm. Furthermore, sulfide consumption was
      also assessed, determining rates of 0.04, 0.13 and 0.005 mmol l(-1) of sulfide
      oxidized at depths of 2.6, 3 and 6 mm, respectively.

PMID- 12207216
TI  - Bacteriological conversion in twenty urinary tuberculosis patients treated with
      ofloxacin, rifampin and isoniazid: a 10-year follow-up study.
AB  - Twenty patients with urinary tuberculosis were treated with ofloxacin (200
      mg/day, 6 months), rifampin (600 mg/day, 3 months) and isoniazid (300 mg/day, 3
      months) between 1989 and 1990. All patients were new cases, diagnosed by
      observation and/or isolation of Mycobacterium tuberculosis in one of the three
      morning urine samples. Bacteriological culture conversion (negativization) was
      assessed as a clinical guide of efficacy, comparing it, as the only parameter,
      against a control group (150 patients) with urinary tuberculosis who received
      conventional therapy. Bacteriological follow-up studies were performed in both
      groups monthly for 6 months, then again 6 months later and then every year for 10
      years after completion of treatment. In the 20 patients, the initial culture was
      positive with over 100 colonies per culture (>50%); the smear was positive in 45%
      of the patients (most were 2+). All strains were susceptible to rifampin,
      isoniazid and ofloxacin. Two patients discontinued treatment. Beginning with the
      first month of treatment, the bacteriological conversion was 100%, 89.5% and 100%
      in the remaining controls. In the control group, which received conventional
      treatment, the conversion was: 90%, 87%, 93% and 100% in the remaining controls.
      Treatment with ofloxacin resulted in a bacteriological conversion similar to that
      following conventional treatment ( p>0.05, Fisher's exact test). After 10 years
      of patient follow-up, we conclude that ofloxacin, in combination with rifampin
      and isoniazid (both for 3 months only is effective against M. tuberculosis,
      providing satisfactory bacteriological and clinical efficacy.

PMID- 12207217
TI  - Proteome analysis of Aspergillus nidulans reveals proteins associated with the
      response to the antibiotic concanamycin A, produced by Streptomyces species.
AB  - Competition between microbes is common to all ecosystems, but the exact nature of
      the competition is in most cases unknown. We have previously studied the
      antagonism between Streptomyces halstedii and several fungi at both the
      organismal and gene expression levels. Here we analysed the effect of an
      antibiotic produced by Streptomyces, concanamycin A, on protein levels in the
      filamentous fungus Aspergillus nidulans. Two-dimensional gel electrophoresis
      revealed that 20 proteins either increased or decreased in abundance upon
      treatment of the fungus with the antibiotic. Five of the most prominent proteins
      which changed in abundance were identified based on peptide analysis by mass
      spectrometry. Two of these correspond to proteins previously described in A.
      nidulans, and three others are homologous to proteins found in other organisms.
      Of these, one down-regulated protein was identified as glyceraldehyde
      dehydrogenase, a protein involved in general metabolic pathways. A second down
      regulated protein, CpcB, affects the initiation of sexual development. Among the
      proteins not previously described in A. nidulans, all of them up-regulated by
      concanamycin A, we found two proteins with described homologues in other fungal
      species. The first is homologous to a cadmium-induced protein in Candida sp. The
      second protein is homologous to LovC, an enoyl transferase involved in the
      biosynthesis of lovastatin, a secondary metabolite identified in A. terreus. A
      third protein has a homologue in A. niger, which is of unknown function. This
      study indicates that proteome analysis may be a useful method for studying
      effects on gene expression during competitive interactions between bacteria and
      filamentous fungi.

PMID- 12207218
TI  - Multiple environmental signals determine the transcriptional activation of the
      mycoparasitism related gene prb1 in Trichoderma atroviride.
AB  - Trichoderma atroviride parasitizes a large variety of phytopathogenic fungi. This
      characteristic has allowed its use as a biological control agent. The production
      of hydrolytic enzymes appears to be a key element in the parasitic process. Among
      the enzymes released by Trichoderma, the proteinase Prb1 plays a major role. We
      show here that the corresponding gene ( prb1) is subject to nitrogen catabolite
      repression. Accordingly, induction of prb1 transcription by Rhizoctonia solani
      cell walls and by osmotic stress requires release from a repressed condition,
      which is determined by nitrogen availability. Furthermore, the transcription
      pattern of the prb1 gene was not affected when an inhibitor of p38-Hog1, a
      regulator of the response to osmotic shock, was used. In contrast, a MEK1/2
      (MAPK/ERK) inhibitor blocked prb1 transcription in response to nitrogen
      limitation, indicating that the pathway employed in the nitrogen response
      involves proteins similar to p42-p44. Fusion of the prb1 promoter to the gfp
      reporter gene allowed the detection of a novel regulatory element, providing an
      initial insight into the nature of the sites that control prb1 expression.

PMID- 12207219
TI  - Genome sequencing of a 239-kb region of rice chromosome 10L reveals a high
      frequency of gene duplication and a large chloroplast DNA insertion.
AB  - In this study we describe a 239-kb region on the long arm of rice chromosome 10
      that contains a high density (71%) of locally duplicated genes, including 24
      copies of a glutathione S-transferase gene. Intriguingly, embedded within this
      cluster is a large insertion (approximately 33 kb) of rice (Oryza sativa)
      chloroplast DNA that is derived from two separate regions of the chloroplast
      genome. We used DNA fiber-based fluorescence in situ hybridization (fiber-FISH)
      analyses of O. sativa spp. japonica nuclei to confirm that the insertion of
      organellar DNA was not a cloning artifact. The sequence of the chloroplast
      insertion is nearly identical (99.7% identity) to the corresponding regions in
      the published rice chloroplast genome sequence, suggesting that the transfer
      event occurred recently. PCR amplification and sequence analysis in two
      subspecies of rice, O. sativa spp. japonica and spp. indica, indicates that the
      transfer event predated the divergence of these two subspecies. The chloroplast
      insertion is flanked by a 2.1-kb perfect direct repeat that is unique to this
      location in the rice genome.

PMID- 12207220
TI  - DNA microarray analysis of fim mutations in Escherichia coli.
AB  - Bacterial adhesion is often mediated by complex polymeric surface structures
      referred to as fimbriae. Type 1 fimbriae of Escherichia coli represent the
      archetypical and best characterised fimbrial system. These adhesive organelles
      mediate binding to D-mannose and are directly associated with virulence in the
      urinary tract. A typical type 1 fimbriated bacterium has up to 500 fimbriae on
      its surface, with each fimbria consisting of approximately 1000 individual
      subunits. This equates to approximately 8% of the total cellular protein and is
      potentially a significant resource drain for the cell. Here we have used DNA
      microarray analysis to examine the molecular events involved in response to
      fimbrial gene expression in E. coli K-12. Observed differential expression levels
      of the fim genes were in good agreement with our current knowledge of the
      stoichiometry of type 1 fimbriae. Changes in fim expression correlated directly
      with alterations in colony morphology. Deletion of the entire fim gene cluster
      resulted in the converse expression of another surface protein Antigen 43 (Ag43).
      Specific deletion of the fimH gene did not affect expression of other fim genes
      or Ag43, but did dramatically reduce the number of fimbriae expressed on the cell
      surface. The use of high-resolution oligonucleotide arrays for defining points of
      transcription initiation and termination is also demonstrated.

PMID- 12207221
TI  - Genomic analysis of the terpenoid synthase ( AtTPS) gene family of Arabidopsis
      thaliana.
AB  - A family of 40 terpenoid synthase genes ( AtTPS) was discovered by genome
      sequence analysis in Arabidopsis thaliana. This is the largest and most diverse
      group of TPS genes currently known for any species. AtTPS genes cluster into five
      phylogenetic subfamilies of the plant TPS superfamily. Surprisingly, thirty AtTPS
      closely resemble, in all aspects of gene architecture, sequence relatedness and
      phylogenetic placement, the genes for plant monoterpene synthases, sesquiterpene
      synthases or diterpene synthases of secondary metabolism. Rapid evolution of
      these AtTPS resulted from repeated gene duplication and sequence divergence with
      minor changes in gene architecture. In contrast, only two AtTPS genes have known
      functions in basic (primary) metabolism, namely gibberellin biosynthesis. This
      striking difference in rates of gene diversification in primary and secondary
      metabolism is relevant for an understanding of the evolution of terpenoid natural
      product diversity. Eight AtTPS genes are interrupted and are likely to be
      inactive pseudogenes. The localization of AtTPS genes on all five chromosomes
      reflects the dynamics of the Arabidopsis genome; however, several AtTPS genes are
      clustered and organized in tandem repeats. Furthermore, some AtTPS genes are
      localized with prenyltransferase genes ( AtGGPPS, geranylgeranyl diphosphate
      synthase) in contiguous genomic clusters encoding consecutive steps in terpenoid
      biosynthesis. The clustered organization may have implications for TPS gene
      evolution and the evolution of pathway segments for the synthesis of terpenoid
      natural products. Phylogenetic analyses highlight events in the divergence of the
      TPS paralogs and suggest orthologous genes and a model for the evolution of the
      TPS gene family.

PMID- 12207222
TI  - A genetic analysis of the porin gene encoding a voltage-dependent anion channel
      protein in Drosophila melanogaster.
AB  - The voltage-dependent anion channel (VDAC, also known as porin) is an abundant
      protein in the outer mitochondrial membrane that forms transmembrane channels
      permeable to solutes. While in mammals at least three different porin genes have
      been found, only one VDAC-encoding gene, porin, has been described so far in
      Drosophila melanogaster. It produces transcripts with alternative untranslated
      sequences. Here we report the identification of two PlacW insertions in the porin
      gene among a set of P-element insertions that have been mapped to the 32B3-4
      region on the second chromosome. Homozygotes, as well as trans-heterozygotes for
      these insertions, lack VDAC, and die during the late pupal stage. Function can be
      restored by precise excision of the P transposon, while most deletions in the
      porin locus, produced by imprecise excisions, display the recessive lethal effect
      of the original mutant alleles. However, one of the deletions was found to be a
      hypomorphic male-sterile allele producing low levels of the VDAC protein,
      indicating that the product of the porin gene is also essential for male
      fertility. Analysis of the new mutant alleles also showed that the untranslated
      exon 1B of the porin gene is not required for VDAC synthesis. In the course of
      our investigation, we found that immediately adjacent to the porin gene are three
      more genes encoding proteins that share homology with the VDAC protein. The
      possible evolutionary and functional relationships of the porin-like genes at
      32B3-4 are discussed.

PMID- 12207223
TI  - A gene that encodes a product with similarity to dioxygenases is highly expressed
      in teliospores of Ustilago maydis.
AB  - The phytopathogenic basidiomycete Ustilago maydis produces sexual teliospores
      only after infection of its host plant, maize. To investigate the process of
      spore formation, we have isolated Ssp1, a protein that is abundantly expressed in
      mature teliospores. The corresponding gene, ssp1, is expressed at low levels in
      haploid sporidia; however, transcriptional levels are drastically induced in
      mature teliospores. Transcriptional regulation of ssp1 involves positive and
      negative promoter elements, and is subject to control by the cAMP signaling
      cascade and histone deacetylase-mediated repression. Ssp1 shows similarity to
      linoleate diol synthase, a fatty acid dioxygenase from the fungus Gaeumannomyces
      graminis. In agreement with this presumed function, Ssp1 is localized on lipid
      bodies in germinating teliospores, suggesting a role in the mobilization of
      storage lipids.

PMID- 12207224
TI  - Mapping of genes controlling aluminum tolerance in rice: comparison of different
      genetic backgrounds.
AB  - Aluminum toxicity is the main factor limiting the productivity of crop plants in
      acid soils, particularly in the tropics and subtropics. In this study, a doubled
      haploid population derived from the rice ( Oryza sativa L.) breeding lines CT9993
      and IR62266 was used to map genes controlling Al tolerance. A genetic linkage map
      consisting of 280 DNA markers (RFLP, AFLP and SSR) was constructed to determine
      the position and nature of quantitative trait loci (QTLs) affecting Al tolerance.
      Three characters - control root length (CRL), Al-stressed root length (SRL) and
      root length ratio (RR) - were evaluated for the DH lines and the parents at the
      seedling stage in nutrient solution. A total of 20 QTLs controlling root growth
      under Al stress and control conditions were detected and distributed over 10 of
      the 12 rice chromosomes, reflecting multigenic control of these traits. The two
      QTLs of largest effect, qALRR-1-1 and qALRR-8 for root length ratio (a
      measurement of Al tolerance) were localized on chromosomes 1 and 8, respectively.
      Three other QTLs in addition to qALRR-8 were apparently unique in the CT9993 x
      IR62266 mapping population, which may explain the high level of Al tolerance in
      CT9993. Comparative mapping identified a conserved genomic region on chromosome 1
      associated with Al tolerance across three rice genetic backgrounds. This region
      provides an important starting point for isolating genes responsible for
      different mechanisms of aluminum tolerance and understanding the genetic nature
      of this trait in rice and other cereals.

PMID- 12207225
TI  - DNA structural variation affects complex formation and promoter melting in
      ribosomal RNA transcription.
AB  - Eukaryotic ribosomal RNA promoters exhibit an unusual conservation of non
      canonical DNA structure (curvature, twist angle and duplex stability) despite a
      lack of primary sequence conservation. This raises the possibility that rRNA
      transcription factors might utilize structural anomalies in their sequence
      recognition process. We have analyzed in detail the interaction of the polymerase
      I transcription factor TIF-IB from Acanthmoeba castellanii with the CORE
      promoter. TIF-IB interacts primarily with the minor groove of the promoter. By
      correlating the effects on transcription and on DNA structure of promoter point
      mutations, we show that the TIF-IB interaction is strongly inhibited by increases
      in minor groove width. This suggests that a particular DNA structure is required
      for interaction with the transcription factor. In addition, TIF-IB induces a
      small bend in the promoter upon binding. Modeling of this bend reveals that it
      requires an additional narrowing of the minor groove, which would favor binding
      to mutants with narrower grooves. We also discuss how this narrowing would induce
      a small destabilization of the helix upstream of the transcription start site.
      Telestability predicts this would result in destabilization of the sequence that
      melts during initiation, suggesting that TIF-IB may have a role in stimulating
      melting.

PMID- 12207226
TI  - Poly(A) site choice during mRNA 3'-end formation in the Schizosaccharomyces pombe
      wos2 gene.
AB  - In the fission yeast Schizosaccharomyces pombe, the wos2 gene encodes p23, a
      highly conserved protein which functions as a co-chaperone for the heat shock
      protein Hsp90. This p23 protein binds to Hsp90, but its activities and regulatory
      mechanisms are still unclear. Northern analysis has shown that the wos2 gene
      produces three transcripts of about 1.1, 0.9 and 0.8 kb, which are expressed
      differentially depending on the growth temperature. The largest and the smallest
      transcripts were most abundant at 25 degrees C, whereas the 0.9-kb transcript
      predominated at 37 degrees C. A time-course analysis indicated that this 0.9-kb
      species rapidly increased in abundance after a shift from 25 degrees C to 37
      degrees C, reaching a maximum after 15 min. A shift back to 25 degrees C resulted
      in a decline in the amount of this transcript, albeit at a slower rate.
      Expression analysis of wos2:ura4 and nmt1:wos2 constructs showed that the 3'
      untranslated region of wos2 alone directs the formation of these multiple,
      discrete wos2 mRNAs. Sequence analysis of cDNAs derived from these mRNAs showed
      that the use of different polyadenylation sites results in the production of the
      three differently sized wos2 transcripts. In the case of the 0.9- and 0.8-kb mRNA
      species, these sites lie in a predicted hairpin loop in the mRNA, suggesting that
      polyadenylation signals in wos2 transcripts may be mediated by RNA secondary
      structure. The possibility that differential thermal stability of these hairpin
      structures could influence polyadenylation site choice during formation of the 3'
      ends of the mRNAs is discussed.

PMID- 12207227
TI  - Structural features and expression analysis of a linear mitochondrial plasmid in
      rapeseed (Brassica napus L.).
AB  - A linear plasmid molecule about 11 kb in length is present in the mitochondria of
      some varieties of rapeseed (Brassica napus L.). This plasmid can be inherited
      from the male parent, through the pollen, as well as by the usual maternal route,
      although the main mitochondrial genome is maternally inherited in rapeseed. We
      determined the complete nucleotide sequence of this plasmid DNA and clarified its
      genetic organization. The length of the linear plasmid is 11,640 bp. At the
      termini of the plasmid molecule are inverted repeats of 327 bp. The GC content of
      the plasmid DNA is 30.9%; thus, the plasmid is quite AT-rich compared to the main
      mitochondrial genome in higher plants. The plasmid has six ORFs, two of which
      encode a phage-type DNA polymerase and a phage-type RNA polymerase, respectively.
      RT-PCR analyses revealed that all six ORFs are transcribed, and all four ORFs on
      the minus strand are probably cotranscribed from a single promoter located in the
      terminal inverted repeat. We also show here that at least three of the six ORFs
      are translated into proteins in rapeseed mitochondria, and expressed at
      relatively high levels in flowers, as shown by Western analysis. These results
      suggest that this linear DNA molecule is able to replicate as an autonomous
      replicon and to express the genes it carries in rapeseed mitochondria.

PMID- 12207229
TI  - Cloning of AFLP markers linked to resistance to Peronosclerospora sorghi in
      maize.
AB  - Genetic mapping of resistance genes for sorghum downy mildew (SDM) in maize
      revealed multiple-locus inheritance. A combination of AFLP (amplified fragment
      length polymorphism) technique with bulked segregant analysis (BSA) was applied
      to map the genes involved in the resistance to SDM (Peronosclerospora sorghi) in
      a recombinant inbred population. Three AFLP markers were identified and mapped to
      chromosomes 1 and 9, in regions previously associated with SDM resistance. One
      other AFLP marker was found to be associated with disease susceptibility but
      could not be linked to any chromosome. These four AFLP fragments were isolated,
      cloned and sequenced. A BLAST search of the GenBank database showed that none of
      these four sequences was closely related to resistance genes that have been
      reported previously. Sequence-characterized amplified regions (SCARs) were
      produced and used to assess the presence of SDM resistance genes and characterize
      specific genotypes. These markers may be useful in marker-assisted breeding
      programs.

PMID- 12207228
TI  - STM1, a gene which encodes a guanine quadruplex binding protein, interacts with
      CDC13 in Saccharomyces cerevisiae.
AB  - The CDC13 gene encodes a protein that binds to the G-rich single-strand at yeast
      telomeres, and serves as a regulator of telomere replication. Cdc13 interacts
      with Est1 and DNA polymerase alpha, and cells carrying the temperature-sensitive
      allele cdc13-1 cannot complete telomere replication at the restrictive
      temperature and possess long telomeres. We attempted to isolate and characterize
      genes that interact with CDC13, in order to clarify the molecular mechanisms of
      telomere replication. A STM1 cDNA was isolated in a two-hybrid screen using CDC13
      as a bait. The temperature-sensitive growth phenotype and the alteration in
      telomere size in cdc13-1 cells were corrected by introduction of the STM1 gene on
      a multicopy vector, but the extended G-rich single-strand overhangs which are
      also characteristic in the cdc13-1 mutant were not affected. Furthermore, we
      found that multiple copies of SGS1, a gene encoding a helicase that can unwind
      guanine quadruplexes, inhibited suppression of the cdc13-1 phenotype by STM1. We
      also demonstrate that a fusion protein consisting of the N-terminal region of
      Cdc13 and the C-terminal region of Stm1 (which shows similarity to the beta
      subunit of the telomere binding complex in Oxytricha) could complement a cdc13
      disruptant. Although STM1 itself is not essential for telomere replication, our
      findings suggest that STM1 genetically interacts with CDC13 to maintain telomere
      structure.

PMID- 12207230
TI  - The Rhizobium etli gene iscN is highly expressed in bacteroids and required for
      nitrogen fixation.
AB  - Sequence analysis of the rpoN (2)- fixA intergenic region in the genome of
      Rhizobium etli CNPAF512 has uncovered three genes involved in nitrogen fixation,
      namely nifU, nifS and nifW. These genes are preceded by an ORF that is highly
      conserved among nitrogen-fixing bacteria. It encodes a putative gene product of
      105 amino acids, belonging to the HesB-like protein family. A phylogenetic
      analysis of members of the HesB-like protein family showed that the R. etli HesB
      like protein clusters with polypeptides encoded by ORFs situated upstream of the
      nifUS nitrogen fixation regions in the genomes of other diazotrophs. The R. etli
      ORF that encodes the HesB-like protein was designated iscN. iscN is co
      transcribed with nifU and nifS, and is preferentially expressed under free-living
      microaerobic conditions and in bacteroids. Expression is regulated by the
      alternative sigma factor RpoN and the enchancer-binding protein NifA. A R. etli
      iscN mutant displays a reduction in nitrogen fixation capacity of 90% compared to
      the wild-type strain. This Nif(-) phenotype could be complemented by the
      introduction of intact copies of R. etli iscN.

PMID- 12207231
TI  - Trans-complementation of an endonuclease-defective tagged I element as a tool for
      the study of retrotransposition in Drosophila melanogaster.
AB  - I factors are non-LTR retrotransposons of Drosophila melanogaster that transpose
      at high frequency in the germline of females resulting from appropriate crosses,
      allowing in vivo studies of the retrotransposition process. Reverse transcription
      of a full-length RNA intermediate is thought to occur at the site of integration,
      using a 3' hydroxyl group generated by endonucleolytic cleavage of the genomic
      DNA to prime synthesis of the first cDNA strand. This target-primed reverse
      transcription (TPRT) process is mediated by endonuclease and reverse
      transcriptase activities encoded by the element. We have designed a molecularly
      tagged, endonuclease-defective I element that can be mobilised with high
      efficiency by constructs that express the product of the I factor ORF2 in trans.
      This indicates that the endonuclease activity required for retrotransposition of
      the I factor can be provided in trans. Using this system, we show that the
      endonuclease domain of the R1Bm retrotransposon from Bombyx mori cannot
      functionally replace that of the I factor.

PMID- 12207233
TI  - New horizons in sequential injection kinetic analysis.
AB  - The need to measure several quantities rapidly in the same sample has prompted
      the development of automated methods of analysis that in both the continuous and
      discontinuous modes offer the possibility of simultaneous determinations. The
      application of pH gradients and differential kinetic determinations dominate the
      simultaneous determination of two or more closely related species in mixtures
      without prior separation. Various options enable use of kinetic-based
      measurements for the simultaneous determination of different analytes in flow
      systems. Some possible general reactions are given and discussed. The scope of
      sequential injection kinetic analysis is illustrated with examples.

PMID- 12207234
TI  - Kinetic determination of aromatic amines at millimolar level.
AB  - A kinetic method for the determination of aromatic amines is reported. The method
      involves the formation of an azo dye between 1-(4-hydroxy-6-methylpyrimidin-2-yl)
      3-methylpyrazolin-5-one and a diazonium salt formed from the amine in the
      presence of nitrite in weakly acidic media. The reaction is monitored via the
      initial rate of change of the absorbance of the azo dye at 420 nm, because this
      is proportional to the aniline concentration. The optimum acidity and
      concentration of reagents were established. The concentration ranges for which
      the calibration lines are linear are quite large. Detection limits were
      estimated. The effect of several metal ions usually present in real samples, e.g.
      waste water, was examined to assess interference.

PMID- 12207235
TI  - Catalytic determination of Pb(II) in the presence of Cu(II).
AB  - A kinetic method is presented to determine micro-molar amounts of Pb(II) from
      various river and wastewater samples, in the presence of trace copper. The
      procedure is based on the catalytic effect of both species on the oxidation of
      mercaptosuccinic acid by chromate in acidic media. The extent of the reaction is
      followed spectrophotometrically at 420 nm and pseudo-first-order rate
      coefficients of the rate-determining step are determined as a function of
      catalyst concentrations. The optimum operating conditions (ionic strength,
      temperature, and concentration of reagents) regarding sensitivity towards lead
      were established. Interference by several ionic species has been studied. The
      effect of Fe(III), the only severe interferent, is suppressed by complexation
      with 1,10-phenantroline. The bi-component calibration model employs an artificial
      neural network to compute the Pb(II) concentration from a k(obsd) value and the a
      priori-known Cu(II) concentration of the sample. Working concentration ranges are
      20-2160 micro g L(-1) for Pb(II) and 80-650 micro g L(-1) for Cu(II),
      respectively. Detection limits are 20 micro g L(-1) Pb(II) and 80 micro g L(-1)
      Cu(II), respectively. The relative standard deviations (3 measurements) for four
      different testing points are lower than 2.5%. The method was applied to samples
      of river and wastewater of the mining region of Baia-Mare, Northern Romania. The
      results were compared to those obtained by an officially standardized AAS method.
      Good agreement was achieved. The method is inexpensive, fairly rapid, and
      sensitive. Its working range covers the exact range of concentrations usually
      encountered in the mentioned geographic area.

PMID- 12207232
TI  - 7th International Symposium on Kinetics in Analytical Chemistry, Bucharest,
      Romania, 26-29 September 2001.

PMID- 12207236
TI  - Biosensors designed for environmental and food quality control based on screen
      printed graphite electrodes with different configurations.
AB  - Graphite electrodes fabricated by screen-printing have been used as amperometric
      detectors in biosensors based on NAD(+)-dependent dehydrogenases, tyrosinase, or
      genetically modified acetylcholinesterases. The mono-enzyme sensors have been
      optimized as disposable or reusable devices for detection of a variety of
      substrates important in the food industry ( D-lactic acid, L-lactic acid,
      acetaldehyde) or in environmental pollution control (phenols and dithiocarbamate,
      carbamate and organophosphorus pesticides). The sensors were prepared in four
      configurations differing in enzyme confinement, enzyme immobilization and
      location of the immobilization agent in the biosensor assembly. Tests on real
      samples have been performed with the biosensors; D-lactic acid and acetaldehyde
      have been detected in wine and phenols in air.

PMID- 12207237
TI  - Kinetic-spectrophotometric determination of theophylline, dyphylline, and
      proxyphylline by use of partial least-squares regression.
AB  - A kinetic-spectrophotometric method for the determination of theophylline,
      dyphylline and proxyphylline, based on their azo coupling reaction with the
      diazonium ion of sulfanilic acid after a treatment with alkali, is proposed. The
      absorbance is recorded from 340 to 600 nm every second during reaction for 90 s,
      and calibration is performed by partial least-squares regression, using first
      derivative spectra values. Mixtures containing 2.5-13 micro g mL(-1) dyphylline
      and proxyphylline, and 2-9 micro g mL(-1) theophylline were successfully resolved
      with root mean squared errors of prediction (RMSEP) of 0.4, 0.3, and 0.2 for
      dyphylline, proxyphylline, and theophylline, respectively. The proposed method
      was satisfactorily applied to the determination of the three compounds in a
      commercially available pharmaceutical preparation and provided results similar to
      those obtained by HPLC.

PMID- 12207238
TI  - Detection of organophosphorus insecticides with immobilized acetylcholinesterase 
      comparative study of two enzyme sensors.
AB  - Two-enzyme systems based on acetylcholinesterase (AChE) - a mono-enzyme system
      based on AChE, with p-aminophenyl acetate as substrate, and a bi-enzyme system
      based on AChE and tyrosinase, with phenyl acetate as substrate - have been
      studied for detection of organophosphate insecticides. The analytical performance
      and detection limits for determination of the pesticides were compared for the
      two AChE configurations. The enzyme loading, pH, and applied potential of the bi
      enzyme system were optimised. When phenyl acetate was used as substrate for AChE
      activity the phenol generated by enzymatic hydrolysis was determined with a
      second enzyme, tyrosinase. Amperometric measurements were performed at 100 mV and
      -150 mV relative to the Ag/AgCl reference electrode for the mono-enzyme and bi
      enzyme systems. Screen-printed sensors were used to detect the organophosphorus
      pesticides paraoxon and chlorpyrifos ethyl oxon; the detection limits achieved
      with phenyl acetate as substrate were 5.2x10(-3) mg L(-1) and 0.56x10(-3) mg L(
      1), respectively.

PMID- 12207239
TI  - Derivative spectrophotometry in the determination of phenyl-beta-naphthylamine
      used as an antioxidant in rubber mixtures.
AB  - A method for the determination of phenyl-beta-naphthylamine (PBN) in ternary
      mixtures by second-derivative spectrophotometry is described. The procedure works
      without any separation step of PBN from the other polymer additives. By applying
      the second-derivative spectrophotometry, Beer's law was valid over the range 0.25
      10 micro g mL(-1). The proposed method has been applied to the determination PBN
      in synthetic ternary mixtures and rubber samples. A comparative study of the
      results obtained using the second and the third-derivative spectrophotometric
      methods is presented and evaluated. The derivative spectrophotometric method
      indicated that the amount of PBN found after extraction from the rubber samples
      was 0.97+/-0.02 g/100 g of sample.

PMID- 12207240
TI  - Determination of para-aminobenzoic acid, a degradation product of procaine
      hydrochloride, by zero-crossing first-derivative spectrometry.
AB  - A first derivative spectrometric method has been developed for the determination
      of the para-aminobenzoic acid (PABA), a related substance and degradation product
      of the local anesthetic procaine hydrochloride (PH). The wavelength selected for
      the determination of para-aminobenzoic acid in the presence of procaine was 290
      nm. At this wavelength the calibration graphs relating the amplitude of the
      signals to the concentration of para-aminobenzoic acid were linear up to 10 mg L(
      1). The detection limit of para-aminobenzoic acid was 0.70 mg L(-1). The method
      is simple and rapid and does not require preliminary treatment of the sample. The
      method was validated.

PMID- 12207242
TI  - Use of MALDI-TOF mass spectrometry to monitor solid-phase synthesis of
      oligonucleotides.
AB  - MALDI-TOF mass spectrometry has been used to characterize solid-supported
      oligonucleotides containing natural and non-natural and non-nucleoside moieties
      and a variety of internucleosidic linkages including phosphate and phosphite
      triesters and H-phosphonate diesters. This technique was used to follow the
      reactions involved in oligonucleotide synthesis; this enabled direct control of
      the elongation and optimization of the coupling process.

PMID- 12207241
TI  - Diffraction-based assay for detecting multiple analytes.
AB  - The principles of diffraction are utilized to enable the simultaneous detection
      of multiple analytes in solution, forming the basis of a multi-analyte sensor.
      Probe molecules are immobilized on a substrate such that each type of molecule
      defines a specific pattern within the same region of substrate. The binding of a
      target molecule to its complementary probe is heralded by a characteristic
      diffraction image. This principle is demonstrated using antibody conjugates.

PMID- 12207243
TI  - Direct analysis of nine pharmaceuticals in culture media by use of cartridge
      separation with electrospray mass spectrometric detection.
AB  - A 2-cm cartridge has been used for separation before electrospray mass
      spectrometric analysis of pharmaceutical compounds in cell culture media,
      alleviating the need for sample extraction and desalting procedures. Nine
      representative pharmaceuticals listed in the biopharmaceutical classification
      system (BCS) were chosen as the candidate compounds and Hank's balanced salt
      solution with Hepes buffer (HBSS-Hepes buffer) was used as the cell-culture
      medium in an effort to study permeability of chemicals through cell monolayers.
      Effects of several conditions, e.g. pH and buffer concentration in the mobile
      phase, flow rate, and temperature on separation efficiency were examined. The
      nine pharmaceuticals were separated within 2 min by use of a 2-cm C(8) cartridge.
      Relative standard deviations (RSD) from repeated analysis within the same day or
      over five days were 0.03-0.2% for retention times and 0.6-5.3% for peak areas;
      antipyrine was used as internal standard. Calibration curves based on peak-area
      measurements were linear over the range 0.1-20 micro mol L(-1). The HBSS-Hepes
      buffer did not interfere with separation and detection; identical separation and
      peak intensity were obtained when the samples were separately prepared in
      distilled water or in the culture medium.

PMID- 12207244
TI  - Calcium ion fluorescence detection using liposomes containing Alexa-labeled
      calmodulin.
AB  - This paper describes the preparation and characterization of calcium ion
      sensitive fluorescent liposomes and their application for the determination of
      calcium ions in aqueous samples. Calmodulin (CaM), a calcium ion-binding protein
      labeled with the fluorophore Alexa-488 is embedded in the membrane of unilamellar
      liposomes. Upon calcium ion binding, calmodulin undergoes a conformational change
      that exposes its hydrophobic core and affects the fluorescence intensity of the
      attached fluorophore. Characterization studies of Alexa-CaM-containing liposomes
      reveal that embedding calmodulin molecules in the bilayer membrane of liposomes
      extends the lifetime of the calcium ion binding activity of calmodulin by about
      fourfold compared to the lifetime of its calcium-binding activity in free
      solution. Moreover, the calcium ion response of Alexa-CaM-containing liposomes is
      about threefold higher than the calcium ion response of Alexa-CaM in solution.
      The improvement in the calcium ion detection properties is attributed to the
      interaction between calmodulin, a membranal protein, and the hydrophobic
      phospholipids of the liposomes. The analytical properties of the calcium ion
      sensitive fluorescent liposomes are discussed.

PMID- 12207245
TI  - Use of phosphobetaine-type zwitterionic surfactant for the determination of
      alkali and alkaline earth metal ions and ammonium ion in human saliva by
      capillary electrophoresis.
AB  - With conventional capillary electrophoresis (CE), it was difficult to directly
      analyze samples containing proteins as a result of the irreversible adsorption of
      proteins onto the inner surface of the capillary column. This difficulty,
      however, was completely overcome by adding N-dodecylphosphocholine (DPC, a
      phosphobetaine-type zwitterionic surfactant) to the background electrolyte (BGE).
      DPC made two essential contributions to the determination of common inorganic
      cations in the protein-containing samples: protein adsorption onto the capillary
      walls was completely avoided, and the resolution of the analyte cations was
      essentially improved. The optimal BGE for analysis of biological samples was
      found to be 5 mM DPC, 5 mM copper(II) acetate/10 mM ethylenediamine (pH 8). The
      detection limits (signal-to-noise ratio =3 and UV at 215 nm) of sodium,
      potassium, calcium, magnesium, and ammonium ions were 25, 31, 24, 45, and 60
      micro M, respectively. These five species of the common inorganic cations in
      human saliva samples were detected successfully within 2 min by the proposed
      system with direct sample injection.

PMID- 12207246
TI  - Determination of xylanase, beta-glucanase, and cellulase activity.
AB  - A simple, robust and highly reproducible method for the determination of
      xylanase, beta-glucanase, and cellulase in commercial feed enzyme preparations is
      described. The method is based on measurement of reducing moieties released by
      the enzymes from arabinoxylan, beta-glucan, or carboxymethylcellulose (CMC) and
      is independent of enzyme standards.

PMID- 12207247
TI  - Derivatization reactions of carbamate pesticides in supercritical carbon dioxide.
AB  - Supercritical fluid carbon dioxide (SC-CO(2)) has been used to dissolve
      derivatizing agents (e.g. heptafluorobutyric anhydride, HFBA, and pyridine),
      which also act as a modifier in the fluid phase, for simultaneous extraction and
      derivatization of carbamates from the sample matrix. The derivatized carbamate
      pesticides (carbaryl, 3-hydroxycarbofuran, carbofuran, aldicarb, methiocarb) were
      then analyzed by GC-ECD or GC-MS with excellent sensitivity. Extraction and
      conversion of the carbamates was complete, as indicated by HPLC with post-column
      hydrolysis and o-phthalaldehyde derivatization then fluorescence detection. GC-MS
      (ion trap) was also used to confirm the formation of the carbamate derivatives.
      Compared with the same HFBA reaction in an organic solvent the derivatization
      reaction time was considerably shorter in SC-CO(2.) The described approach,
      combining both extraction and derivatization, simplifies the analysis of
      carbamate pesticides and eliminates the use of organic solvents associated with
      the derivatization step.

PMID- 12207248
TI  - Correct identification of polychlorinated biphenyls in temperature-programmed GC
      with ECD detection.
AB  - A method has been developed for peak identification of PCBs in GC with ECD
      detection under different temperature programs and isothermal conditions on two
      commonly used columns (DB-5 and DB-1701). This was achieved by means of accurate
      calibration of retention times based on the concept of the relative retention
      index P (i) and retention times of the selected PCB internal standards. The P (i)
      was calculated from the predicted retention times with the database of the
      retention parameters (A, B) and the migration equations. Through comparison of
      the calibrated and experimental retention times of PCBs in technical samples, it
      was shown that the developed method was effective for correct PCB comprehensive,
      quantitative, congener-specific (CQCS) analyses.

PMID- 12207249
TI  - Comparison of the standard SM&T sequential extraction method with small-scale
      ultrasound-assisted single extractions for metal partitioning in sediments.
AB  - A single extraction method based on the reagents employed in the SM&T (standards,
      measurement and testing programme) sequential extraction scheme for partitioning
      of Cd, Cr, Cu, Ni, and Pb in sediments has been developed. Small-scale
      extractions adapted to electrothermal atomic absorption spectrometric
      determinations (i.e. 25 mg mass in 1 mL extractant) have been used for the first
      time in conjunction with selective reagents using conventional operating
      conditions (i.e. conductive heating, magnetic stirring) or ultrasound-assisted
      extraction. Small-scale slurry preparations were implemented for determination of
      the residual/total metal content. The methodology developed enabled drastic
      reduction of extraction times, yielding extractable contents in accordance with
      those obtained by application of the conventional SM&T method, which can be
      regarded as a standard method. An important saving in the amount of sample and
      reagents is also achieved with small-scale extractions. Homogeneity of sediments
      at the mg level proved acceptable - precision was similar for between-batch and
      within-batch measurements. Method development was performed with CRM BCR 601 lake
      sediment for which extractable amounts of several metals are known. An
      application to a "real-world" sediment is also presented.

PMID- 12207250
TI  - Strategies for the analysis of coal by laser ablation inductively coupled plasma
      mass spectroscopy.
AB  - The potential of laser ablation inductively coupled mass spectrometry (LA-ICP-MS)
      was investigated for the inorganic characterization of different coal samples
      pressed into pellets. Reference analysis was performed by microwave-assisted
      digestion of the ground samples followed by ICP-MS analysis of the resulting
      solutions. Two different laser ablation sampling procedures were compared. For
      continuous sampling, three sites of the pellet were sampled for approximately one
      minute, whereas for sequential sampling 15 sites were sampled for two seconds,
      respectively. The qualitative results of the two procedures were equivalent, but
      continuous sampling allowed faster analysis and better precision (RSD about 10%)
      than sequential sampling (RSD 10-20%). Different normalization procedures with
      internal and extrinsic standards were investigated and allowed a quantitative
      determination of Al, Ti, Zn, Ni, and V with measurement uncertainties below 10%
      and Fe, Si, and Sn with measurement uncertainties below 20%.

PMID- 12207251
TI  - Reagent injection FIA system for lead determination by hydride generation -
      quartz-tube atomic absorption spectrometry.
AB  - A method is proposed for the determination of lead by generation of its hydride
      and detection by quartz-tube AAS using a reagent injection FIA system based on
      the injection of sodium tetrahydroborate. Lead hydride generation was carried out
      using a combination of 0.5 M nitric acid, 10% m/ v hydrogen peroxide and 10% m/ v
      sodium tetrahydroborate. The characteristic concentration obtained was 3.1 ng mL(
      1) and the detection limit was 2.6 ng mL(-1) for an injected volume of 0.125 mL
      of tetrahydroborate.

PMID- 12207252
TI  - Sequential spectrophotometric determination of methanol and iron in vinegar by a
      flow injection-pervaporation method.
AB  - An easily automatable sequential flow-injection-pervaporation method is proposed
      for the photometric determination of methanol and iron in vinegar. The method is
      based on separation of the methanol from the sample matrix by pervaporation
      followed by its oxidation to formaldehyde with permanganate, decolouration of the
      latter with S(2)O(5)(2-), and subsequent reaction of formaldehyde with p
      rosaniline to yield a violet reaction product with maximum absorption at 567 nm.
      Iron is determined by an existing method based on reaction with thiocyanate in
      acidic medium and monitoring at 508 nm. After optimisation by either the
      univariate or multivariate approaches, as required, the linear range was
      established for methanol (4-1000 mg L(-1)) and iron (0.18-20 mg L(-1)). The
      proposed method was then compared with reference methods for methanol and iron in
      terms of repeatability (2.452 mg L(-1) and 0.245 mg L(-1), respectively),
      reproducibility (4.435 mg L(-1) and 0.356 mg L(-1), respectively), detection
      limit (LOD=82 and 0.234 mg L(-1), respectively), and traceability. The throughput
      was nine samples per hour.

PMID- 12207253
TI  - Determination of trace bismuth by flow injection-hydride generation collection
      atomic absorption spectrometry.
AB  - Bismuth hydride gas was collected on-line and determined via a new flow injection
      hydride generation collection-flame atomic absorption spectrometry system. The
      performance of the gas-liquid separator, hydride gas collection time, acidity of
      the sample solution, NaBH(4) concentration, and the effects of concomitant
      interferents were investigated to optimize the conditions of this new method.
      Interferences from concomitant elements were investigated, and recoveries of 94.7
      105.3% for 10 ng mL(-1) Bi were obtained after the addition of 0.2% ascorbic acid
      thiourea masking reagents. The sensitivity of this new method was one order of
      magnitude higher than the continuous flow-hydride generation-flame atomic
      absorption method with a detection limit of 0.25 ng mL(-1) and a precision of
      2.3%. The method was evaluated by determining trace bismuth in standard
      biological reference material human hair GBW07601, and the results were
      consistent with the certified value. The proposed method was then employed to
      determine trace bismuth in ten colored gelatin samples; recoveries of 94.2-105.8%
      were obtained.

PMID- 12207254
TI  - On-line pre-concentration of Cr(III) and Mn(II) in FI-FAAS: A critical study
      involving interference effects and analytical use of an immobilized 8
      hydroxyquinoline minicolumn.
AB  - A flow injection system with a pre-concentration minicolumn based on a chelating
      resin was coupled to a flame atomic absorption spectrometer. The focus of this
      work was the investigation of interference effects and the analytical
      applicability of the azo-immobilized 8-hydroxyquinoline on controlled-pore glass
      for the determination of Cr and Mn in mussel and non-fat milk powder. All studied
      concomitants affected the retention of Cr(III). These effects are probably
      related to the formation of hydroxo-complexes at the optimum pH range 9.0-10. The
      positive effect caused by Ca(II) was exploited to increase the retention of
      Cr(III) species and to improve the slope by 70%. The interferences on Mn(II)
      retention were less severe. The quantification of Cr and Mn was performed by
      standard additions. The proposed methodology was validated by analysis of three
      certified reference materials of mussels (Cr and Mn) and non-fat milk powder (Mn)
      with a mean relative percent error of <6.5% and mean relative standard deviation
      of <13%. Chromium and Mn were determined in typical Chilean mussels samples, and
      Mn was determined in non-fat milk powder samples. Results agreed at the 95%
      confidence level with those obtained by electrothermal atomic absorption
      spectrometry (ETAAS) using graphite furnace atomization. The method detection
      limits for a 30 s pre-concentration time were 0.9 and 1.1 micro g L(-1) for Mn,
      and 2.2 and 2.5 micro g L(-1) for Cr in acid digested solutions of mussel and non
      fat milk, respectively. The methodology is simple, fast (sampling frequency 60-72
      h(-1)), reliable, of low cost, and can be applied to the determination of traces
      of Cr (> or =0.18 micro g g(-1)) and Mn (> or =0.6 micro g g(-1)) in mussel
      samples, and Mn (> or =0.37 micro g g(-1)) in non-fat milk powder.

PMID- 12207255
TI  - An on-line potentiometric sequential injection titration process analyser for the
      determination of acetic acid.
AB  - An on-line potentiometric sequential injection titration process analyser for the
      determination of acetic acid is proposed. A solution of 0.1 mol L(-1) sodium
      chloride is used as carrier. Titration is achieved by aspirating acetic acid
      samples between two strong base-zone volumes into a holding coil and by
      channelling the stack of well-defined zones with flow reversal through a reaction
      coil to a potentiometric sensor where the peak widths were measured. A linear
      relationship between peak width and logarithm of the acid concentration was
      obtained in the range 1-9 g/100 mL. Vinegar samples were analysed without any
      sample pre-treatment. The method has a relative standard deviation of 0.4% with a
      sample frequency of 28 samples per hour. The results revealed good agreement
      between the proposed sequential injection and an automated batch titration
      method.

PMID- 12207256
TI  - Use of the simplex method to optimize the mobile phase for the micellar
      chromatographic separation of inorganic anions.
AB  - The sequential simplex strategy has been used to optimize the mobile phase used
      for separation of inorganic anions by micellar chromatography on a C(18)- micro
      Bondapak column, with absorption detection at 230 nm. The amount of acetonitrile
      and the concentration of phosphate buffer (pH 6.0) were chosen for optimization.
      The optimum mobile phase was found to be 38% acetonitrile in 18.2 mmol L(-1)
      phosphate buffer (pH 6.0) containing 10 mmol L(-1) cetyltrimethylammonium bromide
      (CTAB); this optimum was achieved within seven experiments. The separation of the
      five anions (nitrite, nitrate, iodide, thiocyanate, and thiosulfate) was
      accomplished in 18 min.

PMID- 12207257
TI  - Investigation of carrier-mediated anion co-transport through organic membranes by
      use of competitive transport experiments.
AB  - Competitive carrier-mediated co-extraction and co-transport of a variety of
      anions and their counter ions into an organic phase or through supported liquid
      hydrophobic membranes from aqueous mixtures of salts have been monitored by ion
      chromatography. The method enables rapid screening of the anion co-transport or
      co-extraction ability of new potential ionophores and carrier molecules.

PMID- 12207258
TI  - Characterization and determination of piperine and piperine isomers in eggs.
AB  - A new analytical method for the determination of piperine and its isomers in egg
      yolk and albumen is described here. All four isomers were separated by HPLC and
      detected using UV, DAD and electrochemical detection. The absolute detection
      limit (UV detection, S/ N=3) of a standard solution of piperine was 370 pg
      piperine. The correlation coefficients for the linear calibration graphs
      (concentration range: c=100 ng-10 micro g piperine isomer/mL) are generally
      better than 0.996. The piperine isomers were characterized and identified by
      spectroscopy (MS, (1)H-NMR, FT-IR). The method was successfully applied to the
      determination of piperine deposits in eggs (egg yolk and albumen) after feeding
      hens with piperine-spiked feed. The detection limit for piperine (24.8(+/-0.2)
      ng/g egg yolk and 37.9(+/-4.9) ng/g albumen) and the recoveries (70.3(+/-7.7)%
      (egg yolk) and 75.7(+/-1.9)% (albumen)) of piperine were determined.

PMID- 12207259
TI  - Microwave-assisted extraction of zearalenone from wheat and corn.
AB  - A microwave-assisted extraction (MAE) method has been developed for determination
      of zearalenone in wheat and corn by LC-MS with an atmospheric pressure chemical
      ionization interface (APCI). Matrix effects were minimized by use of matrix
      matched standard curves for quantification of the analyte. The limit of
      quantification (LOQ) of the method was 30 ng g(-1) in wheat and 20 ng g(-1) in
      corn. The rapid LC-MS method enabled analysis of the extracts without clean-up,
      thereby reducing analyte losses, the time required for the analytical procedure,
      and costs. A factorial design approach was used to examine the effect on
      extraction efficiency of the main extraction conditions - time, temperature, and
      solvent. On the basis of results from statistical assessment extraction was
      performed with 1:1 (v/v) methanol-acetonitrile at 80 degrees C for 5 min. When
      these extraction conditions were applied to a wheat sample from a recently
      conducted international proficiency test, 92% (103 ng g(-1)) of the assigned
      zearalenone concentration (112 ng g(-1)) in the test material was obtained. This
      result was within the uncertainty (u) range of the assigned value of the test
      material (u=+/-15.8 ng g(-1), alpha=0.05) thereby demonstrating the accuracy of
      the method was sufficient. The precision of the whole method was also confirmed
      to be adequate, because the observed relative standard deviation (RSD) of 12%
      (n=10) also fulfils the quality criteria recommended by European guidelines for
      in-house method validation.

PMID- 12207260
TI  - Determination of yeast assimilable nitrogen content in wine fermentations by
      sequential injection analysis with spectrophotometric detetection.
AB  - An automated method for measuring the primary amino acid concentration in wine
      fermentations by sequential injection analysis with spectrophotometric detection
      was developed. Isoindole-derivatives from the primary amino acid were formed by
      reaction with o-phthaldialdehyde and N-acetyl- L-cysteine and measured at 334 nm
      with respect to a baseline point at 700 nm to compensate the observed Schlieren
      effect. As the reaction kinetic was strongly matrix dependent the analytical
      readout at the final reaction equilibrium has been evaluated. Therefore four
      parallel reaction coils were included in the flow system to be capable of
      processing four samples simultaneously. Using isoleucine as the representative
      primary amino acid in wine fermentations a linear calibration curve from 2 to 10
      mM isoleucine, corresponding to 28 to 140 mg nitrogen/L (N/L) was obtained. The
      coefficient of variation of the method was 1.5% at a throughput of 12 samples per
      hour. The developed method was successfully used to monitor two wine
      fermentations during alcoholic fermentation. The results were in agreement with
      an external reference method based on high performance liquid chromatography. A
      mean-t-test showed no significant differences between the two methods at a
      confidence level of 95%.

PMID- 12207261
TI  - Complex formation between phytic acid and divalent metal ions: a solution
      equilibria and solid state investigation.
AB  - An investigation on the complex formation equilibria between divalent metal ions
      Me (with Me=Mn, Co, Ni, Cu, Cd, and Pb) and phytic acid (H(12)L) is presented.
      Experiments were performed through a potentiometric methodology by measuring, at
      25 degrees C, the proton and, in some cases (Cu(2+), Cd(2+), and Pb(2+)), also
      the metal ion activity at equilibrium in solutions containing, besides the metal
      and the ligand, 3 M NaClO(4) as the ionic medium. Unhydrolyzed solutions of the
      metal ion at millimolar concentration levels were titrated with solutions of
      about 10 mM sodium phytate, until the formation of a solid phase took place
      (always at pH approximately 2.5, except in the case of Cu(2+), which formed
      soluble complexes up to pH approximately 3.3). Coulometry was employed to produce
      very dilute solutions of either Cu(2+), Cd(2+), or Pb(2+) of accurately known
      composition. The emf data were explained by assuming, in the acidity interval
      explored, the formation of the complexes of general stoichiometry MeH(5)L(5-) and
      Me(2)H(3)L(5-). Coordination compounds in the solid state were also synthesized
      and characterized by elemental analysis, thermal analysis, and ICP spectroscopy.
      The solids had a general stoichiometry Me(6)H (t)LCl (t). x H(2)O, with the
      following t and x values for each metal investigated: Me ( t; x) = Mn (4; 2); Co
      (4; 2); Ni (4; 2); Cu (2; 2.5); Zn (2; 1); Sn (6; 6).

PMID- 12207262
TI  - [Role of matrix-degrading enzymes in melanoma progression].
AB  - Cutaneous melanoma is an invasive and early metastazising tumor. Melanoma cells
      detach from the primary tumor, penetrate the basement membrane, invade lymphatics
      and blood vessels, and form metastases. These processes all depend on coordinated
      expression and/or activation of proteolytic enzymes. In addition to aspartyl- and
      cysteineproteinases, serine proteinases including the plasminogen activator
      system (uPA, uPAR, tPA, PAI-1 and PAI-2) and matrix metalloproteinases (MMPs)
      with their tissue inhibitors (TIMPs) play an essential role in these processes.
      In addition, melanoma cells require specific adhesion molecules such as integrins
      and CD44 for interaction with other cells and components of the extracellular
      matrix (ECM); these are also involved in binding activated MMPs on the cell
      surface. In this review we discuss these functional aspects of melanoma
      progression.

PMID- 12207263
TI  - [Perspectives for dermatology in the 21st century].
AB  - During the last decades dermatology has been profoundly transformed from its
      descriptive origin into an important part of modern medicine and biosciences.
      Areas of interest and expertise in the future will likely be focused on major
      topics on clinical dermatology (psoriasis, atopic dermatitis, skin infections
      including those sexually transmitted), dermatologic oncology (squamous cell
      carcinoma, malignant melanoma), gene technology in biopharmacy and
      dermatopharmacology, and also the areas dealing with the aging of the skin and
      its appendages (dermatologic endocrinology, cosmetic dermatology). Increasing
      knowledge in dermatology is not only relevant for treating skin disease but also
      for helping our patients to maintain healthy and appealing skin, thus improving
      their requirements for beautification and their quality of life. While this is an
      important aim, it should not become our main task. Overall, the perspectives for
      dermatology are promising; in the end, its further development will depend on how
      modern societies will recognize its significance and reward its efforts.

PMID- 12207264
TI  - [Verrucae vulgares. Treatment with 585 nm flashlamp pumped pulsed dye laser].
AB  - BACKGROUND AND OBJECTIVE: Various approaches have been taken in the management of
      verrucae vulgares, but a treatment of choice has not been established.
      PATIENTS/METHODS: Over a period of 12 months, 99 Patients with recalcitrant or
      untreated verrucae vulgares on their hands or feet (2:1) were treated with a 585
      nm flashlamp pumped pulsed dye laser (FPDL) every 2 to 4 weeks. Laser parameters
      were: energy density 8 J/cm2, spot size 7 mm, pulse duration 450 microseconds. No
      topical measures were employed during the course of laser treatment. RESULTS: 93
      patients finished the study, as 6 were lost to follow-up. Up to 8 laser
      treatments led to 63% total remission and 22% partial remission, 15% did not
      respond to this type of management. Relapses were not found in a follow-up period
      of 2 to 6 months. CONCLUSIONS: FPDL is efficient for the removal/reduction of
      verrucae vulgares and does not requires less patient compliance than other
      treatment options.

PMID- 12207265
TI  - [Treatment of methicillin-resistant Staphylococcus aureus (MRSA) as part of
      biosurgical management of a chronic leg ulcer].
AB  - Colonization with methicillin-resistant Staphylococcus aureus (MRSA) strains is
      an increasing problem in the treatment of wounds. Only a very limited repertoire
      of effective treatment strategies is available, especially for outpatient care.
      We successfully treated a chronic leg ulcer colonized with MRSA on an ambulatory
      basis, using larvae of the common greenbottle fly Lucilia sericata. Whereas the
      proteases secreted by Lucilia sericata may lead to efficient selective
      necrolysis, the phenylacetate and phenylacetataldehyde may exert antimicrobial
      effects. Treatment with Lucilia sericata represents an effective and inexpensive
      treatment strategy of chronic wounds, especially when colonized with MRSA Due to
      the low acceptance by patients and medical stuff, it is not often employed.

PMID- 12207266
TI  - [Unilateral blepharochalasis with IgA-deposits].
AB  - A 36-year-old male patient presented with unilateral periocular skin atrophy. The
      blepharochalasis developed without any obvious inflammation of the eyelids over
      the past 10 years. Interestingly, elongated blood vessels and microaneurysmatic
      vessel changes were found in the tarsal conjunctiva. A punch biopsy revealed a
      nearly complete loss of elastic fibres in the papillary and superficial reticular
      dermis. The contralateral side was histopathologically normal. On immunohistology
      IgA-deposits could be observed especially on perifollicular elastic fibres.
      Immunoelectronmicroscopy confirmed the diagnosis and suggested fibulin and
      fibronectin as potential binding sites for the autoantibodies. This further
      report of elastolysis in association with IgA-autoantibodies defines the
      autoantibody binding site in more detail and suggests that the immune mechanisms
      may also play a role in vessel changes of the conjunctiva.

PMID- 12207267
TI  - [Malignant atrophic papulosis (Kohlmeier-Degos disease). Failure to respond to
      interferon alpha-2a, pentoxifylline and aspirin].
AB  - A 45 year old female patient presented with the cutaneous manifestations of
      malignant atrophic papulosis (Kohlmeier-Degos disease) for two years. The typical
      papules with central porcelain-white atrophy correspond histologically to wedge
      shaped necrosis of the connective tissue due to thrombotic occlusion of small
      vessels in the corium. The pathogenesis of malignant atrophic papulosis and
      effective treatment modalities are unknown. A slow virus infection has been
      suggested by some authors. Therefore, we attempted an immune therapy with
      interferon alpha-2a over a period of 11 months, but failed to cause a significant
      effect on the appearance and progression of the skin lesions. Furthermore, we
      could not confirm the effectiveness of a recently reported treatment modality
      with pentoxifylline and aspirin administered to our patient over a period of 5
      months.

PMID- 12207268
TI  - [Medical reflections on the Cranach altar in the St. Wolfgang church at
      Schneeberg/Saxony].
AB  - When looking at some figures of the Cranach altar in the St. Wolfgang church at
      Schneeberg/Saxony, congenital syphilis and other diseases must be taken into
      diagnostic consideration. An earlier edition of this magazine contained a
      reference to a quite similar, possibly luetic saddle nose on a carved figure in
      the monastery of Waldsassen, which was made almost 200 years later. For
      iconographical reasons and because of the very early time of its creation around
      1530, the deliberate representation of such a diagnosis, at least for Schneeberg,
      seems doubtful.

PMID- 12207270
TI  - Facing the challenge of treating stuttering in the schools.
AB  - There are many difficult issues facing speech-language pathologists who work with
      school-age children who stutter; however, the challenges are not insurmountable.
      Effective treatment for children who stutter is possible, even in school
      settings. This chapter introduces two issues of Seminars in Speech and Language
      aimed at helping clinicians improve their treatment of stuttering in school-age
      children. The first issue addresses basic aspects of evaluation and treatment,
      including procedures for assessing children's communication abilities, developing
      appropriate goals for therapy, and utilizing a number of specific treatment
      strategies. The second issue addresses special topics in the treatment of school
      age children who stutter, including multicultural factors, concomitant disorders,
      and finding and using helpful resources to enhance treatment. Throughout the two
      issues, the authors will repeatedly emphasize that clinicians can help children
      who stutter become more successful communicators by drawing upon knowledge and
      strategies from a variety of perspectives and by taking a broad-based,
      comprehensive approach to understanding and treating stuttering.

PMID- 12207271
TI  - IDEA '97 and children who stutter: evaluation and intervention that lead to
      successful, productive lives.
AB  - The Individuals with Disabilities Education Act (IDEA) '97 is the federal law
      that shapes the legal process involved with evaluating and treating children who
      stutter. The speech-language pathologist is required to provide a complete
      evaluation of the child's communication skills, including documentation of the
      impact of the child's stuttering on his involvement in his education. Goals and
      benchmarks are written based on the weaknesses identified in the child's present
      level of performance within the Individualized Education Plan (IEP). Transition
      plans are crucial for the child who stutters to become a healthy, productive
      member of society. Therapy frequency and location are based on the child's
      individual needs. Placement, dismissal, and re-enrollment are issues that vary
      for each child who stutters. IDEA '97 provides speech-language pathologists with
      clear direction as to the programming for children with the complex disorder of
      stuttering.

PMID- 12207272
TI  - Diagnosing stuttering in the school environment.
AB  - School speech-language pathologists work in settings that present multiple
      challenges to diagnosing stuttering in students. Perceiving stuttering as a
      communication impairment allows integration of various issues with criteria from
      the Individuals with Disabilities Education Act 1997 into an effective diagnostic
      plan. Assessment from multiple perspectives reveals motor, linguistic, social,
      affective, and cognitive issues related to communication and educational
      competencies. Common sense and pragmatic communication concerns related to
      children who stutter are described. Clinical questions, observations, issues, and
      tasks are explored as parts of the assessment process. The multidimensional
      assessment of student-centered issues helps the clinician determine eligibility
      qualifications, develop individual education plans, and meet full-inclusion
      educational requirements.

PMID- 12207273
TI  - Therapy planning for school-age children who stutter.
AB  - This article offers principles to consider in developing therapy plans for school
      age children who stutter. Goals of speech therapy should be individualized,
      educationally relevant, and lead to functional outcomes that last. Skills and
      experiences gained through speech therapy should help children communicate
      effectively and develop positive attitudes about themselves as communicators. A
      variety of collaborative planning tools are presented to help IEP team members
      prioritize needs based on relative importance of behavioral, cognitive, and
      affective aspects of the stuttering problem from the perspective of the child,
      parents, and teachers. Strategies are included for overcoming some of the
      specific challenges inherent in therapy planning and goal setting for this
      population.

PMID- 12207274
TI  - Speech modification approaches to stuttering treatment in schools.
AB  - The treatment procedures referred to here as "speech modification" are those that
      use a known fluency-inducing condition and that have as an explicit goal teaching
      the client to speak in a manner that will not include stuttering. This paper
      briefly reviews four subcategories of speech modification approaches for children
      in the schools: variations on prolonged speech, extended length of utterance
      approaches, response-contingent approaches, and mixed approaches. Special
      challenges to be faced by clinicians who would like to use speech modification
      procedures in the schools are also addressed.

PMID- 12207275
TI  - Administering stuttering modification therapy in school settings.
AB  - Stuttering modification techniques can be used effectively in the school setting.
      In fact, speech-language pathologists can use this environment to their advantage
      to address not only disfluency but also the emotional and behavioral aspects of
      stuttering. Toward this end, stuttering modification goals and techniques are
      outlined, with a discussion of how to adapt them to school environments. Specific
      topics include writing clear, measurable IEP goals, taking advantage of the
      school setting to implement these goals, administering stuttering modification
      within a group therapy mode, involving parents and teachers, and monitoring
      progress.

PMID- 12207276
TI  - Successful communication for children who stutter: finding the balance.
AB  - For many school-age children, stuttering consists of more than just speech
      disfluencies, physical tension, and struggle. Therefore, successful therapy for
      stuttering should address more than just these observable characteristics. In
      addition to working on fluency goals, clinicians can help children (as well as
      the people in the child's environment) reduce negative reactions to stuttering
      and increase their tolerance and acceptance of their speaking abilities. By
      treating the entire stuttering disorder in this way, clinicians can help children
      reduce barriers to successful communication and improve their overall
      communication skills. When children develop a balance between increased fluency
      and healthy communication attitudes, they have the greatest opportunity for
      becoming successful communicators who can speak freely and with confidence in any
      situation they face.

PMID- 12207277
TI  - Strategies for addressing bullying with the school-age child who stutters.
AB  - This article outlines basic principles for helping school-age children who
      stutter to deal with bullying. Bullying may affect children's school performance
      and feelings of self-worth and lead to depression and feelings of helplessness
      and loneliness. Bullying can also exacerbate stuttering behavior, increase
      negative emotions and negative thoughts, and reduce therapy progress. A variety
      of techniques can be implemented as part of the overall treatment process to help
      children deal with bullying. These techniques can improve children's overall
      success in treatment by helping them develop socially appropriate responses to
      bullying, reduce or prevent negative emotion that may result from stuttering, and
      feel more comfortable in applying speech management skills learned in treatment.

PMID- 12207278
TI  - Stuttering therapy in partnership with support groups: the best of both worlds.
AB  - The current challenges facing school-based speech-language pathologist (SLPs)
      make it increasingly difficult to provide "best practice" services for children
      who stutter. Traditional modes of therapy alone do not meet many of the needs of
      children who stutter and their families. Using an interdisciplinary "team"
      approach to therapy that incorporates support organizations may increase the
      probability of positive outcomes for children who stutter. By facilitating the
      introduction of a support organization experience into the direct therapy
      process, the school-based SLP is uniquely positioned to use this resource to
      complement an overall treatment strategy. Although there is no substitute for a
      competent, professional SLP as the primary care provider in the treatment of
      stuttering, this article outlines some of the many benefits that can be gained by
      partnering with support organizations when treating children who stutter.

PMID- 12207280
TI  - Synthesis of paullones with aminoalkyl side chains.
AB  - Paullones 3 and 4 with aminoalkyl side chains in 2- or 3-position were
      synthesized as derivatives of kenpaullone 1. Both 3 and 4 showed the
      characteristic CDK1-inhibitory activity of the paullones and a modest
      antiproliferative activity on cultured human tumor cell lines. Hence, 3 and 4
      appear to be suitable tools for affinity studies directed to find additional
      intracellular paullone targets.

PMID- 12207281
TI  - Stereoselective synthesis and in vitro antifungal evaluation of (E)- and (Z)
      imidazolylchromanone oxime ethers.
AB  - A series of (E)- and (Z)-2, 3-dihydro-3-(1H-imidazol-1-yl)-4H-1-benzopyran-4-one
      oxime ethers have been synthesized and tested for antifungal activity. Most
      compounds showed moderate to potent in vitro antifungal activity. Among the
      tested compounds, compound (E)-3d was the most active agent against Candida
      albicans and Aspergillus niger, and compounds (Z)-(3a) and (E)-3a were the most
      potent compounds against Microsporum gypseum. Detailed stereoselective synthesis,
      spectroscopic, and biological data are reported.

PMID- 12207282
TI  - Synthesis and evaluation of new elastase substrates as tripartate prodrugs.
AB  - Compounds consisting of a peptide sequence, 4-aminobutyric acid or 5-aminovaleric
      acid, respectively, as spacer units, and benzyl alcohol as a model leaving group
      have been prepared and tested for their ability to serve as substrates for
      porcine pancreatic elastase and human polymorphnuclear elastase. Those compounds
      containing an Ala-Ala-Ala sequence served as effective substrates for both
      enzymes. Hydrolytic cleavage, however, occurred exclusively at the ester bond,
      not at the peptide-spacer bond. In order to direct the cleavage site from the
      ester to the amide bond the peptide sequence was varied. We introduced a proline
      residue in P(3) (in relation to the ester bond) which is known to prevent the
      cleavage of a substrate by elastase. No hydrolysis, however, either of the ester
      bond or of the peptide-spacer bond, was found for these compounds.

PMID- 12207283
TI  - Synthesis and antioxidant properties of novel N-substituted indole-2-carboxamide
      and indole-3-acetamide derivatives.
AB  - A series of N-substituted indole-2-carboxamide and indole-3-acetamide derivatives
      have been prepared and their in vitro effects on rat liver lipid peroxidation
      levels and superoxide anion formation were determined. The results clearly
      demonstrate that indole derivatives 4, 5, 10, 15, 17 are very efficient
      antioxidants compared to alpha-tocopherol.

PMID- 12207284
TI  - Synthesis of new 1-(but-2-ynyl)pyrazoles: containing a pyrrolidine or
      diethylamine moiety and their muscarinic properties.
AB  - The synthesis of two series of 1-(but-2-ynyl)pyrazole containing a pyrrolidine or
      a diethylamine moiety, respectively, is described, together with their muscarinic
      receptor affinities.

PMID- 12207285
TI  - Synthesis and acetylcholinesterase/butyrylcholinesterase inhibition activity of 4
      amino-2, 3-diaryl-5, 6, 7, 8-tetrahydrofuro(and thieno)[2, 3-b]-quinolines, and 4
      amino-5, 6, 7, 8, 9-pentahydro-2, 3-diphenylcyclohepta[e]furo(and thieno)-[2, 3
      b]pyridines.
AB  - The acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) inhibition
      activities of a series of 4-amino-2, 3-diaryl-5, 6, 7, 8-tetrahydrofuro[2, 3
      b]quinolines (10-12)/4-amino-5, 6, 7, 8-tetrahydro-2, 3-diphenylthieno[2, 3
      b]quinoline (14) and 4-amino-5, 6, 7, 8, 9-pentahydro-2, 3
      diphenylcyclohepta[e]furo[2, 3-b]pyridine (13)/4-amino-5, 6, 7, 8, 9-pentahydro
      2, 3-phenylcyclohepta[e]thieno[2, 3-b]pyridine (15) are described. These
      compounds are tacrine (THA) analogues which have been prepared either from
      readily available 2-amino-3-cyano-4, 5-diarylfurans (16-18) or from 2-amino-3
      cyano-4, 5-diphenylthiophene (19), via Friedlander condensation with
      cyclohexanone or cycloheptanone. These compounds are competitive inhibitors for
      acetylcholinesterase, the more potent being compound (13) which is three-fold
      less active than tacrine. The butyrylcholinesterase inhibition activity is
      significant only in compounds 10 and133, which are ten-fold less active than
      tacrine. It is found that the products 11 and 12 strongly inhibit
      acetylcholinesterase, and show excellent selectivity regarding
      butyrylcholinesterase.

PMID- 12207288
TI  - Modelling and optimization of the electrokinetic chromatographic separation of
      mixtures of organic anions and cations using poly(diallydimethyl- ammonium
      chloride) and hexanesulfonate as mixed pseudostationary phases.
AB  - The separation of a series of aromatic carboxylic acids, sulfonates and opiates
      using electrokinetic chromatography employing a mixture of the soluble cationic
      polymer poly(diallydimethylammonium chloride) (PDDAC) and the amphiphilic anion
      hexanesulfonate as pseudostationary phases is described. In this system, the
      PDDAC pseudostationary phase interacts with the anionic analytes, whereas the
      hexanesulfonate pseudostationary phase interacts with the cationic analytes. A
      migration model has been derived which takes into account the ion-exchange (IE)
      interactions between the anions and the cationic PDDAC as well as the ion-pair
      (IP) interactions between the opiates and the hexanesulfonate. A further
      interaction between the combined PDDAC-hexanesulfonate complex and the more
      hydrophobic analytes is also evident and is accounted for in the model. Constants
      obtained by applying the model agreed well with the expected trends in IE
      affinities of the anions for PDDAC and also corresponded with the hydrophobic
      natures of the analytes. Optimization of the PDDAC and hexanesulfonate
      concentrations was performed using the normalized resolution product and minimum
      resolution product criteria. The minimum resolution product criterion proved to
      be most successful. An advantage of the described system is the improvement in
      peak shapes obtained after addition of hexanesulfonate to the electrolyte,
      resulting in increased plate numbers and better resolution. The system was very
      robust with mobilities varying by less than 2% over a period of days and on using
      different capillaries.

PMID- 12207289
TI  - Semi-empirical relationships between effective mobility, charge, and molecular
      weight of pharmaceuticals by pressure-assisted capillary electrophoresis:
      applications in drug discovery.
AB  - Relationships between effective mobility (m(eff)), calculated charge (Z(c)), and
      molecular weight (MW) are semi-empirically derived for pharmaceuticals using
      pressure-assisted capillary electrophoresis (PACE). We determined the m(eff) at
      12 different pH points (2.0-11.4) of 66 pharmaceutical-like compounds ranging in
      MW from 79 to 825 g/mol. Plots of the observed m(eff) values versus Z(c)/MW(x )
      (where x is a fractional coefficient) gave linear relationships. For anions, it
      was found that the best correlation (R(2) = 0.9666) exists when the fractional
      coefficient is equal to 0.4920, resulting in the equation m(eff) = 0.1853
      (Z(c)/MW (0.4920)). For cations, the best linear relationship (R(2) = 0.9861)
      gave the equation m(eff) = 0.3888 (Z(c)/MW (0.6330)). The m(eff), Z(c)/MW(x)
      relationships were then applied to: (i) developing a technique for selecting an
      appropriate pH to achieve optimal separation of pharmaceuticals and (ii)
      determining the maximum charge of a molecule in the pH range of determination of
      negative log of the dissociation constants (pK(a)) by PACE, thus enabling the
      correct choice of model equation to be automated without structure analysis.

PMID- 12207290
TI  - Evalution of capillary electrophoresis-frontal analysis for the study of low
      molecular weight drug-human serum albumin interactions.
AB  - Capillary electrophoresis frontal analysis was applied to 12 low molecular weight
      compounds including 8 drug substances displaying a range of different properties
      with respect to binding affinity, binding location, structure, lipophilicity,
      charge at physiological pH, and electrophoretic mobility. It was found that
      capillary electrophoresis frontal analysis can be used as a general method to
      study and quantify drug-human serum albumin interactions. The binding parameters
      obtained were consistent with literature values. Dextran was in some cases added
      to the run buffer to improve separation of the drug and human serum albumin
      plateau peaks. Results indicate that mobility differences between free and
      complexed human serum albumin give rise to only minor errors. Capillary
      electrophoresis frontal analysis was also found applicable to the study of human
      serum albumin drug displacement reactions. Low sensitivity of the UV-detection
      system was found to be the major limitation of capillary electrophoresis frontal
      analysis. The method is simple, and minimal effort has to be put into method
      development, which makes it well suited for screening in early drug development.

PMID- 12207291
TI  - Kinetic study of gamma-glutamyltransferase activity by electrophoretically
      mediated microanalysis combined with micellar electrokinetic capillary
      chromatography.
AB  - The use of capillary electrophoresis for the determination of gamma
      glutamyltransferase (GGT) activity with gamma-glutamyl-p-nitroanilide (Glu-p-NA)
      as a substrate was investigated. The reaction velocity was quantified
      spectrophotometrically by the corrected peak area of the product p-nitroaniline
      (pNA) at 380 nm. Micelles composed of sodium deoxycholic acid were used in the
      background electrolyte in order to obtain a baseline separation between the
      substrate and the product. The presence of the micelles did not influence the
      enzymatic reaction. The electrophoretic system was used, not only for the
      separation and quantitation of the different reaction compounds but also for the
      in-capillary mixing of the enzyme and substrate plugs. This methodology is known
      as electrophoretically mediated microanalysis (EMMA). With the developed in
      capillary activity assay an average Michaelis constant (K(M)) for GGT was
      calculated to be 2.09 mM (RSD = 7.3%, n = 3), a value consistent with previously
      reported values.

PMID- 12207292
TI  - pH Change of buffer solution in a microcapillary chip and its suppression.
AB  - During the electrophoresis separation of B- and T-cells from lymphocytes
      employing a microcapillary chip, they were found to become inactive in the
      reservoir after a short time. This was caused by the buffer solution becoming
      alkaline due to electrolysis. This was considered to take place in chips with
      small reservoir volumes. The pH change was confirmed by the ISFET (ion-sensitive
      field effect transistor) embedded in the chip. To suppress the pH change, two
      methods were studied. One is the insertion of a salt bridge just in front of and
      behind the capillary, thus introducing an electric potential but stopping flow of
      the acid and alkaline solutions into the capillary. The other is neutralization
      of the alkaline solution in the reservoir by injecting the acid solution produced
      in another capillary with the same structure by employing an electroosmotic flow
      (EOF) pump. Both methods achieved no pH change during electrophoresis
      measurements in the microcapillary.

PMID- 12207293
TI  - On-line conversion and determination of artemisinin using a flow-injection
      capillary electrophoresis system.
AB  - A novel, rapid, and simple capillary electrophoresis (CE) method has been
      developed for the determination of antimalarial artemisinin by on-line treatment
      with alkaline. By on-line reaction, artemisinin was automatically and
      reproducibly converted to the strongly UV-absorbing compound, Q292, by treating
      it with 0.20 mol/L NaOH solution for 3 min at 40 degrees C. Analysis was carried
      out in less than 12 min after conversion of artemisinin in a flow injection (FI)
      system that was coupled to CE equipment via a split-flow interface cell, and a
      sampling frequency of 8 h(-1) is achievable. The on-line conversion method has
      been applied to the determination of artemisinin in the traditional Chinese
      herbal drug Artemisia annua L., and the results are satisfactory.

PMID- 12207294
TI  - Up-scaling capillary zone electrophoresis separations of polydisperse anionic
      polyelectrolytes with preparative free-flow electrophoresis exemplified with a
      soil fulvic acid.
AB  - A scale-up of analytical capillary zone electrophoresis (CZE) to preparative free
      flow electrophoresis (FFE) is described. FFE allows fractionations based on
      charge densities in larger amounts than in CZE, enabling further off-line
      analysis of the fractions. Model compounds (carboxylic acids and polystyrene
      sulfonates) showed a similar behavior in FFE as in CZE. Diffusion and
      electrodynamic distortion effects are more pronounced in FFE than in CZE. A soil
      fulvic acid was analyzed by CZE and fractionated by FFE. A comparison of the FFE
      fractions with CZE measurements of the same sample using the effective mobility
      scale showed good agreement of the two methods.

PMID- 12207295
TI  - Large-volume sample stacking for analysis of ethylenediaminetetraacetic acid by
      capillary electrophoresis.
AB  - A simple, quick, and sensitive capillary electrophoretic technique-large volume
      stacking using the electroosmotic flow (EOF) pump (LVSEP) - has been developed
      for determining ethylenediaminetetraacetic acid (EDTA) in drinking water for the
      first time. It is based on a precapillary complexation of EDTA with Fe(III) ions,
      followed by large-volume sample stacking and direct UV detection at 258 nm. The
      curve of peak response versus concentration was linear from 5.0 to 600.0
      microg/L, and 0.7 to 30.0 mg/L. The regression coefficients were 0.9988 and
      0.9990, respectively. The detection limit of the current technique for EDTA
      analysis was 0.2 microg/L with an additional 10-fold preconcentration procedure,
      based on the signal-to-noise ratio of 3. As opposed to the classical capillary
      zone electrophoresis (CE) method, the detection limit was improved about 1000
      fold by using this LVSEP method. To the best of our knowledge, it represents the
      highest sensitivity for EDTA analysis via CE. Several drinking water samples were
      tested by this novel method with satisfactory results.

PMID- 12207297
TI  - A capillary electrophoresis and off-line capillary electrophoresis/electrospray
      ionization-quadrupole time of flight-tandem mass spectrometry approach for
      ganglioside analysis.
AB  - A systematic study for the optimization and implementation of high-performance
      capillary electrophoresis (HPCE) in conjunction with negative ion electrospray
      ionization-quadrupole time of flight-tandem mass spectrometry (ESI-QTOF-MS/MS)
      for the analysis of complex glycolipids is described. The performance of the
      capillary electrophoresis (CE) and off-line CE/ESI-QTOF-MS approach has been
      explored for screening a complex ganglioside mixture from bovine brain. All
      instrumental and solution parameters demonstrated to require special adjustment
      and to have the most substantial effect on the CE separation, abundance of
      product ions produced in a low-energy collision-induced dissociation (CID)
      process and their detection by MS/MS, when attempting to identify and sequence
      single ganglioside molecular species from CE eluted fractions. Upon optimization
      of the experimental parameters, an efficient methodology emerged providing the
      general basic requirements for combined CE/ESI-MS analysis of this type of
      complex glycoconjugate.

PMID- 12207296
TI  - Considerations on contactless conductivity detection in capillary
      electrophoresis.
AB  - Nearly all analyses by capillary electrophoresis (CE) are performed using optical
      detection, utilizing either absorbance or (laser-induced) fluorescence. Though
      adequate for many analytical problems, in a large number of cases, e.g.,
      involving non-UV-absorbing compounds, these optical detection methods fall short.
      Indirect optical detection can then still provide an acceptable means of
      detection, however, with a strongly reduced sensitivity. During the past few
      years, contactless conductivity detection (CCD) has been presented as a valuable
      extension to optical detection techniques. It has been demonstrated that with CCD
      detection limits comparable, or even superior, to (indirect) optical detection
      can be obtained. Additionally, construction of the CCD around the CE capillary is
      straightforward and robust operation is easily obtained. Unfortunately, in the
      literature a large variety of designs and operating conditions for CCD were
      described. In this contribution, several important parameters of CCD are
      identified and their influence on, e.g., detectability and peak shape is
      described. An optimized setup based on a well-defined detection cell with three
      detection electrodes is presented. Additionally, simple and commercially
      available read-out electronics are described. The performance of the CCD-CE
      system was demonstrated for the analysis of peptides. Detection limits at the
      microM level were obtained in combination with good peak shapes and an overall
      good performance and stability.

PMID- 12207298
TI  - Determination of glycoalkaloids and relative aglycones by nonaqueous capillary
      electrophoresis coupled with electrospray ionization-ion trap mass spectrometry.
AB  - Glycoalkaloids are naturally occurring nitrogen-containing compounds present in
      many species of the family Solanaceae, including cultivated and wild potatoes
      (Solanum spp.), tomatoes (Lycopersicon spp.), etc. These compounds have
      pharmacological and toxicological effects on humans due to their significant
      anticholinesterase activity and disruption of cell membranes. Herein is reported
      the development of a capillary electrophoresis (CE) method using nonaqueous (NA)
      separation solutions in combination with ion trap mass spectrometry (MS and
      MS/MS) detection for the identification and quantification of glycoalkaloids and
      their relative aglycones. A mixture 90:10 v/v of MeCN-MeOH containing 50 mM
      ammonium acetate and 1.2 M acetic acid (applied voltage of 25.5 kV) was selected
      as a good compromise for the separation and detection of these compounds. The
      electrospray MS measurements were carried out in the positive ionization mode
      using a coaxial sheath liquid, methanol-water (1:1) with 1% of acetic acid at a
      flow rate of 2.5 microL/min. Under optimized experimental conditions, the
      predominant ion was the protonated molecular ion ([M+H](+)) of solanidine (m/z =
      398), tomatidine (m/z = 416), chaconine (m/z = 852), solanine (m/z = 868), and
      tomatine (m/z = 1034). MS/MS experiments were carried out systematically by
      changing the relative collisional energy and monitoring the intensities of the
      fragment ions that were not high enough to allow better quantification than with
      the mother ions. The method was used for analyzing glycoalkaloids in potato
      extracts.

PMID- 12207299
TI  - Simultaneous determination of selenium and antimony compounds by capillary
      electrophoresis with indirect fluorescence detection.
AB  - Capillary electrophoresis (CE) with indirect fluorescence detection was used to
      analyze selenium (selenite, selenate, selenomethionine, and selenocystine) and
      antimony (antimonite and antimonate) compounds. The separation was achieved by CE
      in 6 min with a 1.2 mM fluorescein solution at pH 9.5. Fluorescein also
      functioned as a background fluorophore for the indirect detection of these
      nonfluorescent species. Linearity of more than two orders of magnitude was
      generally obtained. Precision of migration times and peak areas was less than
      1.0% and 7.2%, respectively. The concentration limits of detection (CLODs) was in
      the microM range. The detection sensitivity was generally dependent upon the
      transfer ratio (TR, defined as the number of moles of fluorescein ions displaced
      by one mole of analyte ions) of each species.

PMID- 12207300
TI  - Joule heating in packed capillaries used in capillary electrochromatography.
AB  - Effective heat dissipation is critical for reproducible and efficient separations
      in electrically driven separation systems. Flow rate, retention kinetics, and
      analyte diffusion rates are some of the characteristics that are affected by
      variation in the temperature of the mobile phase inside the column. In this
      study, we examine the issue of Joule heating in packed capillary columns used in
      capillary electrochromatography (CEC). As almost all commonly used CEC packings
      are poor thermal conductors, it is assumed that the packing particles do not
      conduct heat and heat transfer is solely through the mobile phase flowing through
      the system. The electrical conductivity of various mobile phases was measured at
      different temperatures by a conductivity meter and the temperature coefficient
      for each mobile phase was calculated. This was followed by measurement of the
      electrical current at several applied voltages to calculate the conductivity of
      the solution within the column as a function of the applied voltage. An overall
      increase in the conductivity is attributed to Joule heating within the column,
      while a constant conductivity means good heat dissipation. A plot of conductivity
      versus applied voltage was used as the indicator of poor heat dissipation. Using
      theories that have been proposed earlier for modeling of Joule heating effects in
      capillary electrophoresis (CE), we estimated the temperature within CEC columns.
      Under mobile and stationary phase conditions typically used in CEC, heat
      dissipation was found to be not always efficient. Elevated temperatures within
      the columns in excess of 23 degrees C above ambient temperature were calculated
      for packed columns, and about 35 degrees C for an open column, under a given set
      of conditions. The results agree with recently published experimental findings
      with nuclear magnetic resonance (NMR) thermometry, and Raman spectroscopic
      measurements.

PMID- 12207301
TI  - Titanium dioxide coated surfaces for capillary electrophoresis and capillary
      electrochromatography.
AB  - The potential of titanium dioxide coatings to control the electroosmotic flow and
      to affect the migration behavior of analytes in capillary electrophoresis and
      open-tubular capillary electrochromatography was evaluated. The inner wall of a
      fused-silica capillary was applied with a solution of a titanium peroxo complex,
      followed by heating at an elevated temperature. The resultant product was
      ascertained to be titanium dioxide in a crystalline form of anatase by the
      results of Fourier transform-infrared spectrometry (FT-IR), X-ray photoelectron
      spectroscopy, and Raman spectroscopy. The capillary thus made had anodic or
      cathodic electroosmotic flow, depending on the pH and composition of the
      background electrolyte used. The titanium dioxide surface of the capillary was
      readily modified by a silanizing reagent. The performance of the titanium dioxide
      surfaces with or without chemical modifications was examined with inorganic
      anions, neutral compounds and peptides.

PMID- 12207302
TI  - Capillary electrochromatography with monolithic stationary phases: 1. Preparation
      of sulfonated stearyl acrylate monoliths and their electrochromatographic
      characterization with neutral and charged solutes.
AB  - A novel monolithic stationary phase having long alkyl chain ligands (C17) was
      introduced and evaluated in capillary electrochromatography (CEC) of small
      neutral and charged species. The monolithic stationary phase was prepared by the
      in situ copolymerization of pentaerythritol diacrylate monostearate (PEDAS) and 2
      acrylamido-2-methyl-1-propanesulfonic acid (AMPS) in a ternary porogenic solvent
      consisting of cyclohexanol/ethylene-glycol/water. While AMPS was meant to support
      the electroosmotic flow (EOF) necessary for transporting the mobile phase through
      the monolithic capillary, the PEDAS was introduced to provide the nonpolar sites
      for chromatographic retention. Monolithic columns at various EOF velocities were
      readily prepared by conveniently adjusting the amount of AMPS in the
      polymerization solution as well as the composition of the porogenic solvent. The
      monolithic stationary phases thus obtained exhibited reversed-phase
      chromatography behavior toward neutral solutes and yielded a relatively strong
      EOF. For charged solutes (e.g., dansyl amino acids), nonpolar as well as
      electrostatic interaction/repulsion with the monoliths were observed in addition
      to electrophoretic migration. Therefore, for charged solutes, selectivity and
      migration can be readily manipulated by changing various parameters including the
      nature of the monolith and the composition of the mobile phase (e.g., pH, ionic
      strength and organic modifier). Ultrafast separation on the time scale of seconds
      of 17 different charged and neutral pesticides and metabolites were performed
      using short capillary columns of 8.5 cm x 100 microm ID.

PMID- 12207303
TI  - Comparison of different setups for one- and two-dimensional capillary high
      performance liquid chromatography and pressurized capillary electrochromatography
      coupled on-line with mass spectrometry.
AB  - A comparison of different separation methods (high-performance liquid
      chromatography (HPLC), capillary HPLC (CHPLC) and pressurized capillary
      electrochromatography (pCEC)) coupled on-line with mass spectrometry (MS) is
      undertaken using the separation of a crude extract of ergot fungus (secalis
      cornuti) as an example. New and simple setups for a two-dimensional CHPLC coupled
      on-line with electrospray ionization (ESI)-MS (2D-CHPLC-MS) as well as for
      capillary size-exclusion chromatography performed under pCEC conditions and
      coupled on-line with ESI-MS (CSEC-pCEC-MS) are shown. In addition, an improved
      method for column packing is presented.

PMID- 12207304
TI  - On-line coupling of packed capillary electrochromatography with coordination ion
      spray-mass spectrometry for the separation of enantiomers.
AB  - Pressure-supported packed capillary electrochromatography (CEC) and packed
      capillary high-performance liquid chromatography (pHPLC) have been coupled on
      line to electrospray ionization-mass spectrometry (ESI-MS) and coordination ion
      spray-mass spectrometry (CIS-MS). Separation of enantiomers of barbiturates and
      chlorinated alkyl phenoxypropanoates were performed on a permethylated beta
      cyclodextrin stationary phase by pressure-supported CEC. For on-line detection
      with ESI- and CIS-MS, a modified sheath-liquid interface was used. CIS-MS is a
      universal, novel ionization technique which improves the selectivity as well as
      the sensitivity. Charged complexes were formed through the addition of central
      complexing ions such as silver(I), cobalt(II), copper(II), and lithium(I) to the
      sheath flow. Advantages of CIS-MS detection compared to the ESI-MS mode are
      discussed. In the CIS-MS mode, increased sensitivity and high selectivity was
      attained through different possibilities of complexation. The superiority of
      pressure-supported CEC compared to pHPLC in the hyphenation with CIS-MS is
      demonstrated.

PMID- 12207305
TI  - Physically adsorbed chiral stationary phase of avidin on monolithic silica column
      for capillary electrochromatography and capillary liquid chromatography.
AB  - The physical adsorption method proposed previously has been successfully applied
      to a monolithic silica column. By virtue of the physical adsorption, a chiral
      stationary phase of avidin was prepared onto the silica monolith. The phase ratio
      of resulting stationary phase was evaluated with frontal analysis. The method
      proved to be comparable in phase ratio to the chemical bonding methods used in
      high-performance liquid chromatography (HPLC). Enantiomer separations were
      carried out in capillary electrochromatography (CEC) and capillary liquid
      chromatography (CLC) modes. Due to its larger phase ratio, the resulting column
      showed more powerful separation capability as compared to open-tubular CEC
      (OTCEC). Twelve chiral compounds were baseline-resolved. The resulting column
      showed high separation efficiency, with average theoretical plate numbers of 66
      000/m for CLC and 122 000/m for CEC. Good reproducibility was observed, with RSD
      value less than 1.3% for retention time, retention factor and separation factor,
      and less than 6.6% for plate counts and resolution (n = 40). Fast separations
      were achieved with a short column. The test enantiomers were baseline-resolved
      within 4 min under CLC and CEC modes. In addition, field-enhanced sample
      injection (FESI) was coupled to CLC as well as CEC to improve the detection
      sensitivity.

PMID- 12207306
TI  - Multimodal open-tubular capillary electrochromatographic analysis of amines and
      peptides.
AB  - This study describes a comparison of different modes of open-tubular
      electrochromatography (OTCEC) in bare and etched capillaries. To carry out the
      investigation, the separation of impurities of two synthetic peptides and the
      separation of a mixture of five heterocyclic aromatic amines were studied. Three
      different types of stationary phase were evaluated: (i) fluorosurfactants
      (anionic and zwitterionic) adsorbed in the inner wall of the capillary
      (electrochromatography with dynamically modified stationary phases (DMS)CEC);
      (ii) physically adsorbed polymers (DMA-SO(3-) and DMA-N(+)(CH(3))(3)) and (iii)
      chemically modified capillaries (C(18), cholesteryl 10-undecanoate and diol). The
      results confirm that electrochromatography can be a viable alternative to
      capillary electrophoresis (CE) and liquid chromatography, more established
      separation techniques. It is possible to differentiate some minor species for the
      synthetic peptides that cannot be resolved by CE or high-performance liquid
      chromatography (HPLC). Moreover the separation of the amine mixture depends
      strongly on the stationary phase used.

PMID- 12207307
TI  - A new type of capillary column for open-tubular electrochromatography.
AB  - A new type of open-tubular C(18) ester-bonded electrochromatographic column was
      prepared with sol-gel technology, followed by an on-column octadecyl silylation
      reaction. Glycidoxypropyltrimethoxysilane, a widely used and important silane
      agent, was used as the sol-gel precursor to form a thin coating layer on the wall
      of the fused-silica capillary. The C(18) groups were introduced into the coating
      layer by on-column esterification reaction with stearic acid. The
      electrochromatography behavior of the column was evaluated in terms of the
      separation of peptides. A high efficiency of 4.8x10(5) plates/m was achieved for
      a basic pentapeptide using the C(18 )ester-bonded column. In comparison with bare
      capillaries and glycidoxypropyltrimethoxysilane sol-gel-coated capillaries, the
      C(18) ester-bonded column showed the best separation of a mixture of seven
      pentapeptides under identical conditions of buffer, pH, and applied voltage.

PMID- 12207308
TI  - Combinatorial enantiomeric separation of diverse compounds using capillary array
      electrophoresis.
AB  - Combinatorial chiral separations were performed on a 96-capillary array
      electrophoresis system. A comprehensive enantioseparation protocol employing
      neutral and sulfated cyclodextrins as chiral selectors for common basic, neutral
      and acidic compounds was developed. By using only four judiciously chosen
      separation buffers, successful enantioseparations were achieved for 49 out of 54
      test compounds spanning a large variety of pK and structures. Therefore, unknown
      compounds can be screened in this manner to identify the optimal enantioselective
      conditions in just one run.

PMID- 12207309
TI  - Influence of structure and chirality of the selector on the chiral recognition of
      amino acids using ligand-exchange capillary electrophoresis.
AB  - The dependence of the chiral recognition ability and enantiomer migration order
      on the structure, substitution pattern and chirality of chiral selectors used in
      ligand-exchange capillary electrophoresis is investigated. As chiral selectors
      different N-alkyl derivatives of proline and hydroxyproline as their copper(II)
      complexes are used. The influence of the position and conformation of the hydroxy
      group in the hydroxyproline derivatives and of the structure and chirality of the
      side chain on enantioselectivity is investigated. Furthermore, the effect of
      surfactants such as sodium dodecyl sulfate and cetyl trimethyl ammonium bromide
      on resolution and enantiomer migration order is studied. The investigations were
      carried out with three aromatic amino acids as model compounds.

PMID- 12207310
TI  - Illustration of a simple and versatile scheme for reversing enantiomeric elution
      order and facilitating enantiomeric impurity determination in capillary
      electrophoresis.
AB  - Determination of enantiomeric purity is most often done under overload
      conditions, which leads to deformed peaks. In general, the best resolutions are
      obtained when the small peak appears before the large peak in the
      electropherogram. To be able to determine the R(+)-impurity in the S(-)-form as
      well as the S(-)-impurity in the R(+)-form the elution orders have to be
      reversed. The present paper describes reversal of enantiomeric elution order for
      the basic analyte propranolol and the acidic analyte ibuprofen. For propranolol,
      a charged heptakis-(6-sulfo)-beta-cyclodextrin (CD) is used in the background
      electrolyte. For ibuprofen, a mix of the charged heptakis-(6-sulfo)-beta-CD and
      the uncharged heptakis-(2,3,6-tri-O-methyl)-beta-CD is used in the background
      electrolyte. The use of a coated capillary and reversal of the polarity shift the
      elution order, buffer composition is unchanged in both cases. The enantiomers of
      propranolol and ibuprofen are well separated on both the coated and uncoated
      capillaries. Detection limits of enantiomer impurities are investigated using
      spiked samples of both propranolol and ibuprofen.

PMID- 12207311
TI  - Octakis-6-sulfato-gamma-cyclodextrin as additive for capillary electrokinetic
      chromatography of dibenzoazepines: carbamazepine, oxcarbamazepine and their
      metabolites.
AB  - Single isomer octakis-(2,3-dihydroxy-)6-sulfato-gamma-cyclodextrin used as
      pseudostationary phase of the background electrolyte interacts with
      dibenzo[b,f]azepines (consisting of a condensed 3-ring system) and forms
      negatively charged complexes. Hydroxygroups in position 2 and 3 at carbamazepine
      increase the extent of interaction, whereas substitution by oxygen at position 10
      and/or 11 reduces it. The complex constants for the analytes are ranging from few
      tens L/mol (10-hydroxycarbamazepine, 10,11-dihydroxycarbamazepine, 10,11
      epoxycarbamazepine, oxcarbazepine) to several hundreds L/mol (carbamazepine, 2
      hydroxycarbamazepine, 3-hydroxycarbamazepine), and are much larger than those of
      the analytes with octakis-(2,3-dimethyl-)-6-sulfato-gamma-cyclodextrin. Full
      enantiomeric separation of the chiral metabolites of carbamazepine and
      oxcarbazepine is obtained at octakis-(2,3-dihydroxy-)-6-sulfato-gamma
      cyclodextrin concentrations of about 10 mM (3 mM borate buffer, pH 8.5). Compared
      to heptakis-6-sulfato-beta-cyclodextrin, selectivity differs and
      stereoselectivity is more pronounced.

PMID- 12207312
TI  - Comparative enantioseparations with native beta-cyclodextrin and heptakis-(2-O
      methyl- 3,6-di-O-sulfo)-beta-cyclodextrin in capillary electrophoresis.
AB  - Twenty-three cationic chiral analytes were resolved in capillary electrophoresis
      using native beta-cyclodextrin and single isomer heptakis-(2-O-methyl-3,6-di-O
      sulfo)-beta-cyclodextrin as chiral selectors. For 12 of 16 chiral analytes
      resolved with both chiral selectors the enantiomer migration order was opposite.
      In selected cases the structure of cyclodextrin-analyte complexes in aqueous
      solution was investigated using one-dimensional transverse rotating frame nuclear
      Overhauser and exchange spectroscopy. It was found that in contrast to mainly
      inclusion-type complexes between chiral analytes and beta-cyclodextrin, external
      complexes are formed between the chiral analytes and structurally crowded, highly
      charged heptakis-(2-O-methyl-3,6-di-O-sulfo)-beta-cyclodextrin.

PMID- 12207313
TI  - Enantioseparation of amino acid derivatives by capillary zone electrophoresis
      using vancomycin as chiral selector.
AB  - The separation of racemic derivatized amino acids (N-acetyl) into their
      enantiomers was achieved using capillary zone electrophoresis employing
      vancomycin as a chiral selector. Due to the strong absorption properties of the
      chiral selector at the low wavelengths used, the partial-filling countercurrent
      method was adopted in order to improve method sensitivity. In the separation
      system studied, the chiral selector filled only a part of the capillary and, due
      to the appropriate selection of the pH, was moving in the opposite direction of
      the analytes keeping the detector free from absorbing compounds. The effect of
      several experimental parameters on the enantioresolution of analytes was studied,
      e.g., vancomycin concentration (0-5 mM), pH of the background electrolyte (pH 4
      7), capillary temperature (15-35 degrees C), and the presence of an organic
      modifier in the run buffer (methanol or ethanol or n-propanol). N-Acetyl glutamic
      acid, serine, cystine, tyrosine, and proline were all baseline-resolved into
      their enantiomers and the enantioresolution factor (R(s)) was increased by
      raising the vancomycin concentration. pH 4 allowed the baseline resolution of the
      five studied analytes in the presence of 2.5 mM of chiral selector and an
      increase in pH caused a decrease of R(s).

PMID- 12207314
TI  - Enantioselective analysis of ibuprofen in human plasma by anionic cyclodextrin
      modified electrokinetic chromatography.
AB  - This paper reports the development of a rapid method for the enantioselective
      analysis of the nonsteroidal anti-inflammatory drug ibuprofen in human plasma by
      capillary electrophoresis employing the anionic cyclodextrin-modified
      electrokinetic chromatography mode. Sample cleanup was carried out by
      acidification with HCl followed by liquid-liquid extraction with
      hexane:isopropanol (99:1 v/v). The complete enantioselective analysis was
      performed within 10 min, using 100 mmol L(-1) phosphoric acid/triethanolamine
      buffer, pH 2.6, containing 2.0% w/v sulfated beta-cyclodextrin as chiral
      selector; fenoprofen, another nonsteroidal anti-inflammatory drug, was used as
      internal standard. The calibration curves were linear over the concentration
      range of 0.25-125.0 microg mL(-1) for each enantiomer of ibuprofen. The mean
      recoveries for ibuprofen enantiomers were up to 85%. The enantiomers studied
      could be quantified at three different concentrations (0.5, 5.0 and 50.0 microg
      mL(-1)) with a coefficient of variation and relative error not higher than 15%.
      The quantitation limit was 0.2 microg mL(-1) for (+)-(S)- and (-)-(R)-ibuprofen
      using 1 mL of human plasma. The plasma endogenous compounds and other drugs did
      not interfere with the present assay. The analysis of real plasma samples
      obtained from a healthy volunteer after administration of 600 mg of racemic
      ibuprofen showed a maximum plasma level of 29.6 and 39.9 microg mL(-1) of (-)-(R)
      and (+)-(S)-ibuprofen, respectively, and the area under plasma concentration
      time curve AUC(0-infinity) (+)-(S)/AUC(0-infinity) (-)-(R) ratio was 1.87.

PMID- 12207315
TI  - Methods for fractionation, separation and profiling of proteins and peptides.
AB  - In the last few years there has been an increased effort to develop technologies
      capable of identifying and quantifying large numbers of proteins expressed within
      a cell system (i.e., the proteome). The complexity of the mixtures being analyzed
      has made the development of effective fractionation and separation methods a
      critical component of this effort. This review highlights many of the protein and
      peptide fractionation and separation methods, such as electrophoresis and high
      performance liquid chromatography (HPLC), which have experienced significant
      development over the past forty years. Modern instrumental strategies for the
      resolution of cell proteins, based on separations employing a single high
      resolution or multidimensional approach, and the relative merits of each, will be
      discussed. The focus of this manuscript will be on the development of
      multidimensional separations such as two-dimensional polyacrylamide gel
      electrophoresis (2D-PAGE), HPLC/HPLC, and HPLC-capillary electrophoresis and
      their application to the characterization of complex proteome mixtures.

PMID- 12207316
TI  - DNA sequencing of close to 1000 bases in 40 minutes by capillary electrophoresis
      using dimethyl sulfoxide and urea as denaturants in replaceable linear
      polyacrylamide solutions.
AB  - The goal of this work was to reduce the capillary electrophoresis (CE) separation
      time of DNA sequencing fragments with linear polyacrylamide solutions while
      maintaining the previously achieved long read lengths of 1000 bases. Separation
      speed can be increased while maintaining long read lengths by reducing the
      separation matrix viscosity and/or raising the column temperature. As urea is a
      major contributor to the separation buffer viscosity, reducing its concentration
      is desirable both for increase in the separation speed and easier solution
      replacement from the capillary. However, at urea concentrations below 6 M, the
      denaturing capacity of the separation buffer is not sufficient for accurate base
      calling. To restore the denaturing properties of the buffer, a small amount of an
      organic solvent was added to the formulation. We found that a mixture of 2 M urea
      with 5% v/w of dimethyl sulfoxide (DMSO) resulted in 975 bases being sequenced at
      70 degrees C in 40 min with 98.5% accuracy. To achieve this result, the software
      was modified to perform base-calling at a peak resolution as low as 0.24. It is
      also demonstrated that the products of thermal decomposition of urea had a
      deleterious effect on the separation performance at temperatures above 70 degrees
      C. With total replacement of urea with DMSO, at a concentration of 5% v/w in the
      same linear polyacrylamide (LPA)-containing buffer, it was possible to increase
      the column temperature up to 90 degrees C. At this temperature, up to 951 bases
      with 98.5% accuracy could be read in only 32 min of separation. However, with
      DMSO alone, some groups of C-terminated peaks remained compressed, and column
      temperature at this level cannot at present be utilized with existing commercial
      instrumentation.

PMID- 12207317
TI  - Analysis of aminophospholipid molecular species by methyl-beta-cyclodextrin
      modified micellar electrokinetic capillary chromatography with laser-induced
      fluorescence detection.
AB  - Micellar electrokinetic capillary chromatography (MEKC) with laser-induced
      fluorescence detection is used for the analysis of three classes of
      aminophospholipids: phosphatidylethanolamine (PE), phosphatidylserine (PS), and
      lysophosphatidylethanolamine (LPE) molecular species. 3-(2-Furoyl) quinoline-2
      carboxaldehyde (FQ), a fluorogenic dye, was employed for labeling of these
      phospholipids. The FQ-labeled lipid species were then separated by sodium
      deoxycholate MEKC modified with methyl-beta-cyclodextrin. Baseline resolution of
      each class of phospholipids was achieved within 7 min. The migration time in each
      class increased with the carbon number of their side aliphatic chain. Separation
      efficiencies of approximately 3x10(5) plates were observed for most of these
      species. Concentration detection limits (3 sigma) were from 10(-9) to 10(-10) M
      for PE and LPE species and from 10(-8) to 10(-9) M for PS species. The relative
      standard deviations for migration time and peak area were less than 0.9% and
      4.5%, respectively, for seven PE species. This method was applied to the
      separation of PE isolated from HT29 human colon cancer cells and roughly 30 PE
      species were resolved.

PMID- 12207318
TI  - Determination of residues of enrofloxacin and its metabolite ciprofloxacin in
      chicken muscle by capillary electrophoresis using laser-induced fluorescence
      detection.
AB  - A method for the residue analysis of the veterinary antimicrobial agent
      enrofloxacin and its active desethyl metabolite ciprofloxacin in chicken muscle
      tissue has been developed and validated. The detection of the analytes was
      performed by laser-induced fluorescence (LIF) detection using a HeCd laser
      (lambda(ex) = 325 nm) providing an enhancement in sensitivity and selectivity
      compared to conventional UV detection. The assay has been validated with
      satisfying results. The limits of quantification for enrofloxacin and
      ciprofloxacin were 5 microg/kg and 20 microg/kg, respectively, with a fivefold
      preconcentration yielded by a sample clean-up with a simple liquid-liquid
      extraction procedure. Calibration graphs were linear from 5 to 1000 microg/kg for
      enrofloxacin and from 20 to 1000 microg/kg for ciprofloxacin. The assay allows
      the detection of contaminated muscle samples at the required maximum residue
      limit of the European Union, which is 100 microg/kg for the sum of enrofloxacin
      and ciprofloxacin.

PMID- 12207319
TI  - Separation of alkamides from Echinacea purpurea extracts by cyclodextrin-modified
      micellar electrokinetic chromatography.
AB  - Separation of nine important alkyl methylbutyl- and isobutylamides (known as
      alkamides) obtained from Echinacea purpurea extracts was investigated by using
      cyclodextrin-modified micellar electrokinetic chromatography (CD-MEKC).
      Hydrophobic alkamides interact strongly with the micelles from the most common
      surfactants used in MEKC and this lead to predominant partition of the analytes
      into the micellar phase, resulting in poor resolution. The addition of neutral
      CDs to the alkaline (10 mM phosphate buffer pH 8.0) micellar system of sodium
      dodecyl sulfate (SDS), sodium cholate (SC) and sodium deoxycholate (SDC) was
      found to improve the separation of the studied alkamides. Among the several
      combinations surfactant/CD, three different systems showed to be particularly
      effective: SDS/hydroxypropyl-beta-CD (110 mM/100 mM) and SC/heptakis (2, 3, 6-tri
      O-methyl)-beta-CD (200 mM/40 mM) which provided a complete separation of the
      studied compounds, and SDC/heptakis (2, 6-di-O-methyl)-beta-CD. The importance of
      appropriate surfactant vs. CD concentration ratio as well as that of total
      concentration of both surfactant and CD was considered. The optimization of the
      separation was performed by focussing the need for a rapid separation of nine
      alkamides diagnostically useful to define the fingerprint of Echinacea species.

PMID- 12207322
TI  - On cross-priming of MHC class I-specific CTL: rule or exception?

PMID- 12207324
TI  - Vitamin E inhibits IL-4 gene expression in peripheral blood T cells.
AB  - IL-4 plays a pivotal role in the development of allergic inflammation via
      induction of IgE isotype switching, increase of IgE receptor expression,
      promoting Th2 cell differentiation, and stimulating several genes involved in
      atopic disorders. Previous studies in human and mouse models have shown that high
      vitamin E intake correlates with low IgE concentration and reduced prevalence of
      allergic reactions. We, therefore, investigated the mechanism of the vitamin E
      effect on T cells. We show here that the natural free radical scavenger vitamin E
      suppresses IL-4 protein levels in human peripheral blood T cells in a dose
      dependent manner. The effect of vitamin E on IL-4 expression occurs at the mRNA
      level. Vitamin E has been implicated in inhibition of DNA binding and function of
      the redox-regulated transcription factors NF-kappaB and AP-1. Investigation of
      the molecular mechanism by which vitamin E suppresses IL-4 transcription shows
      that it blocks binding of transcription factors to two important IL-4 promoter
      binding sites for NF-kappaB and AP-1 and interferes with promoter activity upon T
      cell activation. Our data provide molecular evidence supporting the beneficial
      effect of dietary vitamin E on atopic disorders.

PMID- 12207323
TI  - Endothelin-2 is a macrophage chemoattractant: implications for macrophage
      distribution in tumors.
AB  - Endothelins (ET-1, ET-2 and ET-3) are 21-amino acid vasoactive peptides that bind
      to G-protein-linked transmembrane receptors, ET-RA and ET-RB. As well as
      modulating vasoconstriction, endothelins regulate growth in several cell types
      and may also affect differentiation, inflammation and angiogenesis. Both
      macrophages and endothelins are found in areas of hypoxia in solid tumors and ET
      2 expression may be modulated by hypoxia in some tumors. As the peptide structure
      of mature endothelins is similar to that of CXC chemokines, we asked if
      endothelins contribute to control of macrophage distribution in tumors. We found
      that ET-2 is a chemoattractant for macrophages and THP-1 monocytic cells, but not
      for freshly isolated monocytes. The chemotactic response to ET-2 shows a typical
      bell-shaped response curve. Experiments with endothelin receptor antagonists
      showed that migration to ET-2 is mediated via the ET-RB receptor. Moreover,
      monocytes do not express ET-RB. Chemotaxis towards ET-2 is via the MAPK pathway:
      p44 and p42 are phosphorylated when THP-1 cells are stimulated with ET-2, and the
      MAPKK inhibitor PD98059 stops chemotaxis. As with 'classical' chemokines,
      migration toET-2 is also inhibited by hypoxia and by pertussis toxin. As well as
      its chemotactic properties, ET-2 leads to activation of macrophages. In human
      breast tumors that express ET-2, endothelins and ET-RB expressing macrophages
      often co-localized. While shorter than 'classical' chemokines, ET-2 shares a
      similar peptide sequence with chemokines and may signal via a similar receptor
      and MAPK-mediated pathway. Furthermore, ET-2 expression by tumors may modulate
      the behavior of macrophages such that activated cells accumulate in areas of
      hypoxia.

PMID- 12207325
TI  - Extracellular adenine nucleotides modulate cytokine production by human monocyte
      derived dendritic cells: dual effect on IL-12 and stimulation of IL-10.
AB  - To clarify the functional consequences of adenine nucleotides action on human
      monocyte-derived dendritic cells (DC), we have systematically compared the
      effects of adenosine 5'-O-(3-thiotriphosphate) (ATPgammaS), an ATP analog active
      on the P2Y(11) receptor, on the responses to three DC stimuli, TNF-alpha, LPS,
      sCD40L, tested at various concentrations, using two different IL-12 assays. We
      observed that ATPgammaS potentiated the IL-12p40 release induced by TNF-alpha,
      but also by lipopolysaccharides (LPS) and soluble CD40 ligand (sCD40L). This
      potentiation was observed as long as the IL-12p40 concentration under agonist
      stimulation remained below a threshold value close to 10 ng/ml; inhibition was
      observed above this value. The combinations ATPgammaS-TNF-alpha and ATPgammaS
      sCD40L were unable to induce detectable bioactive IL-12p70 production and at
      concentrations of LPS that induced a significant stimulation of IL-12p70, the
      effect of ATPgammaS was purely inhibitory. Our results also show that ATPgammaS
      synergized with LPS and sCD40L, but not TNF-alpha, to stimulate IL-10 production.
      In conclusion, we have clarified the discrepancies in the literature concerning
      the action of adenine nucleotides on DC and our study supports the concept that,
      like prostaglandin E(2) and other agents increasing cyclic AMP, they favor either
      a Th2 response or tolerance.

PMID- 12207326
TI  - HLA-G inhibits the functions of murine dendritic cells via the PIR-B immune
      inhibitory receptor.
AB  - Human histocompatibility leukocyte antigen (HLA)-G is an MHC class Ib molecule
      that has been proposed to regulate immune responses during pregnancy. One of the
      possible mechanisms of that modulation is based on its interaction with
      immunoglobulin-like transcript (ILT) receptors. In this study, we show that HLA-G
      modifies the function of murine dendritic cells via interactions with the paired
      immunoglobulin-like inhibitory receptor, a homologue of the human inhibitory
      receptor ILT4. Triggering of the immune inhibitory receptors resulted in
      prolongation of allogeneic graft survival. This demonstration forms the basis for
      exploring and exploiting HLA-G molecules and immune inhibitory receptors in the
      development of a new therapeutic strategy to improve allogeneic graft survival.

PMID- 12207327
TI  - IgVH gene analysis suggests that peritoneal B cells do not contribute to the gut
      immune system in man.
AB  - The contribution of peritoneal B cells to the intestinal lamina propria plasma
      cell population is well documented in mice, but unknown in humans. We have
      analyzed immunoglobulin (Ig) genes of human peritoneal B cells, because such
      genes show distinctive characteristics in mucosal B cells, particularly highly
      mutated variable regions. Here, we report the characteristics of variable region
      genes used by IgM, IgA and IgG in peritoneal cells. We focused on the properties
      of IgV(H)4-34 to allow comparisons of like-with-like between different isotypes
      and cells from different immune compartments. We observed that the IgM genes were
      mostly unmutated, and that the mutated subset had less mutations than would be
      expected in a mucosal B cell population. Likewise, the IgV(H)4-34 genes used by
      IgA and IgG from peritoneal B cells had significantly lower numbers of mutations
      than observed in the mucosal counterparts. Other trends observed, while not
      reaching statistical significance, followed the trend of peripheral B cells. The
      peritoneal B cell population had more IgA1 than IgA2 sequences, and there was no
      dominance of J(H)4 in the IgA from peritoneum or spleen, in contrast to the
      mucosal sequences. Overall, this study suggested that human peritoneal B cell are
      either peripheral or mixed in origin; they are unlikely to represent an inductive
      compartment for the mucosal B cell system.

PMID- 12207328
TI  - Human lung myofibroblasts as effectors of the inflammatory process: the common
      receptor gamma chain is induced by Th2 cytokines, and CD40 ligand is induced by
      lipopolysaccharide, thrombin and TNF-alpha.
AB  - The common gamma (gamma c) chain, shared by Th1 and Th2 cytokines, is fundamental
      for the activation of hematopoietic cells, but its role in non-hematopoietic
      tissues has not been explored. Here we show that in normal lung fibroblasts IL-4
      and IL-13 induce the expression of the gamma c chain and its association with
      Janus kinase (JAK) 3, while lung myofibroblasts constitutively express a gamma c
      chain displaying a limited association with JAK3. In the latter cells, without
      exogenous cytokines, gamma c/JAK3 controls, through autocrine loops, tyrosine
      kinase (TYK) 2 phosphorylation and the balance between functional (IL-4Ralpha, IL
      13Ralpha 1) and decoy (IL-13Ralpha 2) high-affinity receptors. Moreover, JAK3 is
      also associated with a pre-phosphorylated IL-4Ralpha and CD40. This novel
      "heterotrimer" (p-IL-4Ralpha, CD40/JAK3) is functional and controls STAT3
      phosphorylation and CD40 expression, as shown by use of the specific JAK3
      inhibitor WHI-P31. In basal culture conditions, CD40 signaling could be induced
      by the transient establishment of inter-fibroblastic CD40/CD40 ligand (CD40L)
      functional bridges. Indeed, powerful pro-inflammatory stimuli such as
      lipopolysaccharide and thrombin can rapidly mobilize CD40L at the surface of lung
      myofibroblasts. These interactions are modified by IL-13, which triggers the
      formation of a new type of functional receptor (p-IL-4Ralpha /IL-13Ralpha 1/gamma
      c) and also the recruitment and the phosphorylation of JAK3. Treatment with JAK3
      inhibitors blocks IL-13-induced phosphorylation of JAK2, TYK2 and STAT3, but not
      of JAK1 and STAT6. These data underline (1) the pivotal role of the gamma c
      chain, CD40/CD40L, JAK3 and IL-13 in the inflammatory-like activation of lung
      myofibroblasts, (2) the cell-type restraint effects of IL-13 on these cells, and
      (3) the potential usefulness of JAK3 inhibitors in the treatment of asthma.

PMID- 12207329
TI  - Organ-specific distribution of CD4+ T1/ST2+ Th2 cells in Leishmania major
      infection.
AB  - Activated CD4(+) T helper cells (Th) comprise at least two functionally distinct
      subsets, Th1 and Th2, which mediate different immunological effector functions.
      Experimental leishmaniasis is widely used to study the effector function of Th
      cell subsets in vivo. Healing and nonhealing Leishmania major infections have
      been correlated with polarized Th1 and Th2 responses, respectively. In the study
      presented here, a stable cell surface marker expressed on Th2 cells, T1/ST2, has
      been used to assess the distribution of CD4(+) T1/ST2(+) T cells in different
      organs of healer and nonhealer strains of mice during the course of L. major
      infection. The frequency of CD4(+) T cells expressing the T1/ST2 cell surface
      marker and Th2 cytokines in the lymphoid organs was low in both strains of
      infected mice; however, CD4(+) T1/ST2(+) T cells could be enriched from the
      lymphoid organs of infected nonhealer but not from healer strains of mice. The
      highest frequency of CD4(+) T1/ST2(+) T cells was detected in the footpads of
      mice with nonhealing disease, showing that CD4(+) T1/ST2(+) T cells home to the
      footpads. Since the majority of parasites persist at the local site of infection
      in nonhealing BALB/c mice, these results show that CD4(+) T1/ST2(+) T cells are
      localized at the site of active infection and inflammation in this model.

PMID- 12207330
TI  - Role of chlamydial heat shock protein 60 in the stimulation of innate immune
      cells by Chlamydia pneumoniae.
AB  - Chlamydia pneumoniae stimulates potently maturation of and cytokine secretion by
      bone marrow-derived dendritic cells (BMDDC). BMDDC responses depend mainly on
      Toll-like receptor (TLR)2 and to a minor extent on TLR4. We demonstrate here
      using C. pneumoniae in an infectious model with the replication-permissive
      epithelial cell line HEp2 that HSP60 is produced in substantial amounts in
      chlamydial inclusions during infection. Electron microscopy of chlamydial
      inclusions revealed that HSP60 was mainly associated with reticulate bodies, but
      was also located in between the different chlamydial developmental forms.
      Supernatants of permissive HEp2 cells infected with C. pneumoniae contained
      soluble chlamydial HSP60 as demonstrated by Western blotting and were able to
      stimulate BMDDC of wild-type mice. The stimulatory capacity of culture
      supernatants correlated with the presence of chlamydial HSP60. In contrast, BMDDC
      from TLR4-mutant mice crossed to TLR2-deficient mice were not stimulated by the
      culture supernatant, indicating that chlamydial HSP60 but not cytokines, possibly
      secreted by infected HEp2 cells, are responsible for the observed stimulation of
      BMDDC. Purified recombinant HSP60 from C. pneumoniae stimulated BMDDC in a TLR2-
      and TLR4-dependent fashion similar to the whole microorganism. In summary, these
      data suggest chlamydial HSP60 as an important mediator of inflammatory responses
      during infection with C. pneumoniae.

PMID- 12207332
TI  - CD22 regulates early B cell development in BOB.1/OBF.1-deficient mice.
AB  - BOB.1/OBF.1 (also called OCA-B), a B lymphocyte-specific transcriptional
      coactivator, is recruited to octamer-containing promoters by interacting with the
      Oct-1 or Oct-2 proteins. BOB.1/OBF.1-deficient mice show impaired secondary
      immunoglobulin isotype secretion and complete absence of germinal centers.
      Furthermore, numbers of splenic B cells are reduced due to a developmental block
      at the transitional B cell stage in the bone marrow. We found that surface
      expression of CD22 is selectively increased on B lineage cells in the bone marrow
      of BOB.1/OBF.1-deficient mice. CD22 is known as a negative regulator of B cell
      receptor signaling. We therefore investigated whether defects in B cell
      development in the BOB.1/OBF.1-deficient mice might be due to CD22 up-regulation.
      Mice were generated lacking both genes. In BOB.1/OBF.1xCD22 double-deficient
      mice, numbers of transitional B cells in the bone marrow were normal.
      Consequently, double-deficient mice also had normal B to T cell ratios in the
      spleen. We show that BOB.1/OBF.1(-/-) B cells were incapable to induce BCR
      triggered Ca(2+) mobilization. This Ca(2+)-signalling defect was restored in
      BOB.1/OBF.1xCD22 double-deficient B cells. Nevertheless, double-deficient animals
      were unable to mount humoral immune responses and to form germinal centers.
      Finally, we demonstrate that CD22(-/-) splenic B cells proliferate independently
      of BOB.1/OBF.1 upon stimulation with LPS. These studies suggest that the B cell
      differentiation defect observed in BOB.1/OBF.1(-/-) mice is BCR-signal dependent.
      However, the impairment in germinal center formation is caused by a different
      mechanism.

PMID- 12207331
TI  - Caspase inhibitors induce a switch from apoptotic to proinflammatory signaling in
      CD95-stimulated T lymphocytes.
AB  - CD95 is a major apoptosis receptor that induces caspase activation and programmed
      cell death in susceptible cells. CD95-induced apoptosis can be blocked by
      peptidic caspase inhibitors such as benzyloxycarbonyl-Val-Ala-Asp-fluoromethyl
      ketone or Ile-Glu-Thr-Asp-fluoromethyl ketone. Here we show that stimulation of
      CD95 in the presence of these inhibitors induces necrosis and expression of
      various proinflammatory cytokines in primary T lymphocytes, such as TNF-alpha,
      IFN-gamma and granulocyte/macrophage colony-stimulating factor. In the absence of
      caspase inhibition CD95 stimulation did not result in cytokine expression,
      indicating that this proinflammatory signaling pathway is suppressed by active
      caspases. Further analysis with A3.01 T cells revealed that the proinflammatory
      signaling activity of CD95 was mediated by MEK/ERK, p38 and NF-kappaB signaling
      pathways. These findings point to a pivotal role of caspases not only as
      mediators of apoptosis but also as enzymes that prevent proinflammatory signaling
      during CD95-induced apoptosis. Moreover, our findings may be useful for the
      development of novel pharmacological strategies.

PMID- 12207333
TI  - Antigen-induced cell death of T effector cells in vitro proceeds via the Fas
      pathway, requires endogenous interferon-gamma and is independent of perforin and
      granzymes.
AB  - Activation of resting T cells usually leads to their proliferation and
      differentiation into effector cells and a subsequent decline following
      elimination of the antigen. A situation of excessive antigen density may result
      in T cell receptor (TCR)-induced deletion of T effector cells, a process termed
      antigen-induced cell death (AgICD). Previous studies indicate that AgICD of
      cytotoxic T cells may be induced by either of the two key cytotoxic processes,
      granule exocytosis, including perforin and granzymes, or the Fas ligand
      (FasL)/Fas pathway. By using in vitro-polyclonally activated or ex vivo-derived
      virus-induced T cell populations from mice with mutations or targeted gene
      defects in one or more components of the two key cytolytic pathways we now show
      that TCR-induced apoptosis is only impaired in the absence of FasL and/or Fas,
      but not in the absence of perforin and/or granzymes. Furthermore, antibody
      blockage of FasL alone is sufficient to inhibit early T cell death. Inhibition of
      both, FasL and tumor necrosis factor (TNF-alpha) is required to abrogate late
      apoptosis by AgICD. The fact that antibodies to IFN-gamma also inhibit AgICD
      suggests that the perforin plus granzyme-independent and FaSL and/or TNF-alpha
      facilitated process of AgICD of T effector cells is tightly regulated by
      endogenous IFN-gamma.

PMID- 12207334
TI  - Constitutive active p21ras enhances primary T cell responsiveness to Ca2+ signals
      without interfering with the induction of clonal anergy.
AB  - Chronic engagement of the T cell receptor mediates the induction of T lymphocyte
      unresponsiveness called clonal anergy. The development of such unresponsiveness
      has been suggested as one of the mechanisms that regulate peripheral tolerance to
      self-antigens and hamper the capacity of tumor antigen-specific T cells to
      eliminate cancerous cells. In the attempt to enhance the effector function of
      CD4(+) T lymphocytes and their resistance to clonal anergy induction, we have
      transduced primary T cells with a retroviral vector encoding active p21(ras)
      (Ras(Leu61)). Here we show that Ras(Leu61) elicited TCR-independent activation of
      the Ras-Raf-ERK pathway and conferred primary T cells with the ability to secrete
      IL-2 in response to stimulation with a Ca(2+) ionophore alone, without altering
      antigen-, CD3/CD28- and PMA/ionomycin-driven IL-2 secretion and T cell
      proliferation in vitro. However, chronic engagement of the TCR onthe surface of
      Ras(Leu61) T cells still led to an inability of the cells to produce IL-2 upon
      restimulation. These results indicate that enforced p21(ras) functionality
      enhances primary T cells responses to calcium-generated signals, but is
      insufficient to prevent TCR-driven T cell unresponsiveness and suggest that
      additional biochemical mechanisms, independent of p21(ras), negatively regulate
      IL-2 production in unresponsive T cells.

PMID- 12207335
TI  - Recognition of core and flanking amino acids of MHC class II-bound peptides by
      the T cell receptor.
AB  - CD4 T cells recognize peptides bound to major histocompatibility complex (MHC)
      class II molecules. Most MHC class II molecules have four binding pockets
      occupied by amino acids 1, 4, 6, and 9 of the minimal peptide epitope, while the
      residues at positions 2, 3, 5, 7, and 8 are available to interact with the T cell
      receptor (TCR). In addition MHC class II bound peptides have flanking residues
      situated outside of this peptide core. Here we demonstrate that the flanking
      residues of the conalbumin peptide bound to I-A(k) have no effect on recognition
      by the D10 TCR. To study the role of peptide flanks for recognition by a second
      TCR, we determined the MHC and TCR contacting amino acids of the I-A(b) bound
      Ealpha peptide. The Ealpha peptide is shown to bind I-A(b) using four alanines as
      anchor residues. TCR recognition of Ealpha peptides with altered flanking
      residues again suggested that, in general, no specific interactions occurred with
      the peptide flanks. However, using an HLA-DM-mediated technique to measure
      peptide binding to MHC class II molecules, we found that the peptide flanking
      residues contribute substantially to MHC binding.

PMID- 12207336
TI  - Unconventional NK1.1(-) intermediate TCR cells as major T lymphocytes expanding
      in chronic graft-versus-host disease.
AB  - Chronic graft-versus-host disease (GVHD) accompanying autoimmune disease was
      induced in (C57BL/6xDBA/2) F(1) mice (H-2(b/d)) by an injection of splenic T
      cells of parental DBA/2 origin (H-2(d)). In parallel with the onset of
      proteinuria, an expansion of lymphocytes was induced in the liver and kidney,
      showing a peak at 2 weeks after the onset of disease. The majority of lymphocytes
      were of recipient origin (H-2(b/d)). The main lymphocyte subset among T cells at
      the pre-onset stage and after the onset of disease was CD8(+) NK1.1(-) CD3(int)
      cells (of extrathymic, hepatic origin) in both the liver and kidney. NK1.1(-)
      CD3(int) cells confer primarily neither NK-like nor NKT-like cytotoxicity. No
      induction of these types of cytotoxicity was observed in these mice with the
      expansion of NK1.1(-) CD3(int) cells. This raised the possibility that
      granulocytes induced in the liver and kidney might be associated with tissue
      damage. The present results suggest that, similarly to the case of autoimmune
      prone mice with genetic background (e.g. MRL-lpr/lpr mice and BXSB mice), NK1.1(
      ) CD3(int) cells of extrathymic, hepatic origin might be crucial lymphocytes
      involved in the induction of the autoimmune-like disease in mice with chronic
      GVHD, in conjunction with Bcells (e.g. B-1 cells).

PMID- 12207337
TI  - Trafficking of CD44-deficient murine lymphocytes under normal and inflammatory
      conditions.
AB  - CD44 has been implicated in hyaluronan (HA)-dependent primary adhesion between
      leukocytes and endothelium. We studied the trafficking of lymphocytes of CD44
      deficient DBA/1 mice under normal conditions, and during chronic and transient
      forms of inflammation. Animals homozygous for the CD44 mutation (CD44(-/-))
      showed no abnormalities in the composition of the lympho-hemopoietic system, but
      their leukocytes could not recognize HA as an adhesion ligand. T cells from CD44
      deficient mice responded normally to immunization with type II collagen or
      stimulation with a bacterial superantigen. Lymphocytes harvested from naive CD44(
      /-) and wild-type (WT) animals showed similar trafficking properties when
      injected into naive recipients. However, cells from WT and CD44-deficient mice
      with collagen-induced arthritis showed distinct migration kinetics upon transfer
      to arthritic recipients. While lymphocytes from CD44(-/-) mice preferentially
      homed to lymph nodes, their entry into the inflamed synovial joints was delayed
      as compared with WT cells. Similar differences were observed in the migration
      kinetics of CD44-deficient and CD44-competent (CD44(+/+)) lymphocytes in
      bacterial superantigen-induced peritonitis. These results suggest that CD44 plays
      opposite roles in the regulation of leukocyte traffic to inflammatory sites
      versus the lymph nodes. CD44-deficient lymphocytes from animals with chronic
      arthritis, but not from those with transient peritonitis, expressed markedly
      reduced levels of the lymph node homing receptor, L-selectin. Extreme down
      modulation of L-selectin from CD44(-/-) cells in arthritic condition might be a
      counter-regulatory response, which, by extending lymphocyte transit time in the
      circulation at the expense of lymph node homing, allows CD44-deficient cells to
      gain entry to the site of chronic inflammation via secondary adhesion mechanisms.

PMID- 12207338
TI  - Bacterial fimbriae activate human peripheral blood monocytes utilizing TLR2, CD14
      and CD11a/CD18 as cellular receptors.
AB  - Bacterial fimbriae are associated with a specific adherence factor, adhesin, in
      their microbial etiology. Porphyromonas gingivalis, as an anaerobic Gram-negative
      periodontopathogenic organism, is known to possess fimbriae on its cell surfaces.
      In this study, we demonstrated that P. gingivalis fimbriae and an active
      synthetic peptide composed of residues 69 - 73 of thefimbrial subunit protein,
      ALTTE, induced IL-6 mRNA expression and cytokine production, p38 mitogen
      activated protein (MAP) kinase phosphorylation, and NF-kappaB activation in human
      peripheral blood monocytes. P. gingivalis fimbriae and ALTTE also induced IL-6
      production via human Toll-like receptor (TLR) 2, CD14, and CD11a/CD18 (LFA-1)
      molecules on human monocytes. These results suggest that P. gingivalis fimbriae
      and these degraded peptides may play an important role in the inflamed gingival
      and periodontal tissues seen in the development and progression of periodontal
      diseases.

PMID- 12207339
TI  - Tissue-specific expansion of NKT and CD5+B cells at the onset of autoimmune
      disease in (NZBxNZW)F1 mice.
AB  - Natural killer T (NKT) cells and CD5(+)B cells were searched for in various
      immune organs of autoimmune prone (NZBxNZW)F(1) (NZB/W F(1)) mice. The number of
      lymphocytes increased in the liver, spleen, and peritoneal cavity after the onset
      of disease (at the age of 30 weeks) while the number of thymocytes decreased at
      that time. Prominent changes of lymphocyte subsets were seen in the liver and
      peritoneal cavity, namely, expansion of IL-2Rbeta(+)TCRalpha beta(int) cells in
      the liver and of CD5(+)B220(+) cells in the peritoneal cavity. The majority of
      TCRalpha beta(int) cells in the liver were NK1.1(+), and CD5(+)B cells in the
      peritoneal cavity were CD1d(+). Proteinuria became prominent in NZB/W F(1) mice
      with the progression of disease. In parallel with this progression, the
      proportion of NKT cells decreased slightly in the liver, but their absolute
      number remained at a high level in this organ. These NKT cells were CD4(+) and
      used an invariant chain of Valpha14Jalpha281 for TCRalpha. Reflecting the
      elevation of CD5(+)B cells, autoantibodies against hepatocyte cytoplasmand
      denatured DNA were detected in sera. Although NKT cells are known to be
      immunoregulatory cells in some autoimmune mice, the present results raise the
      possibility that NKT cells as well as CD5(+)B cells might be associated with the
      onset of autoimmune diseases in NZB/W F(1) mice. Indeed, NKT cells in F(1) mice
      had a high potential to induce autoimmune-like inflammationwhen alpha
      galactosylceramide was administered or when active NKT cells were transferred
      into young F(1) mice.

PMID- 12207340
TI  - Pulmonary T cells induced by respiratory syncytial virus are functional and can
      make an important contribution to long-lived protective immunity.
AB  - The contribution of T cell responses to immunity against respiratory syncytial
      virus (RSV) is not fully defined, but this is an important issue for vaccine
      design. Recent studies demonstrating RSV-induced pulmonary T cell suppression
      suggest that RSV may have evolved strategies to escape T cell immunity. Here we
      evaluated potential consequences of RSV-mediated immunosuppression for protective
      memory T cell responses in vivo. Surprisingly, we found strong ex vivo cytolytic
      activity and interferon production of pulmonary RSV-specific CD8(+) T cells both
      in the acute and the memory phase of primary murine RSV infection. More
      significantly, T cell memory made an important contribution to immunity against
      RSV independent of antibodies. Thus, RSV-primed mice were protected against
      challenge with RSV-recombinant vaccinia viruses, which can be controlled by RSV
      specific T cells, but not by RSV-specific antibodies. In conclusion, RSV does not
      appear to impair acute and protective memory T cell responses induced by a
      primary infection. These findings further support that induction of T cell
      immunity should be a relevant goal for RSV vaccines.

PMID- 12207341
TI  - Differential presentation of group A streptococcal superantigens by HLA class II
      DQ and DR alleles.
AB  - Superantigens have been implicated as pivotal mediators of severe invasive group
      A streptococcal (GAS) infections, by virtue of their potent immunostimulatory
      activity. HLA polymorphism has been suggested to influence the susceptibility to
      severe invasive GAS infection. Here we studied the influence of allelic and
      isotypic variation of HLA class II molecules on GAS superantigen-induced immune
      responses using cells derived from patients with bare lymphocyte syndrome,
      untransfected or transfected with various HLA class II alleles. Significantly
      higher proliferative responses were detected when streptococcal pyrogenic
      exotoxin (Spe) A was presented by cells expressing DQA1*0101/DQB1*0302 (DQ3.2),
      as compared to cells expressing DR1, DR4, or DR5 alleles (p=0.0002-0.01). In
      contrast to SpeA, SpeC was preferentially presented by DR4 as compared to DQB1*03
      (p=0.04). In agreement with the proliferation results, a significantly higher
      frequency of IL-2-, TNF-alpha-, TNF-beta-, and IFN-gamma-producing cells was
      detected when SpeA was presented by HLA class II DQB1*03 alleles as compared to
      DR4 (p=0.0002-0.04). Binding experiments showed a high affinitybinding of SpeA to
      both class II DR4 and DQB1*0302, and there was no significant difference in SpeA
      binding affinity between the two alleles. The data confirm the effect of allelic
      polymorphism in superantigen responses and show that different superantigens are
      preferentially presented by distinct class II alleles.

PMID- 12207342
TI  - Targeting of CD45 protein tyrosine phosphatase activity to lipid microdomains on
      the T cell surface inhibits TCR signaling.
AB  - CD45, a transmembrane protein tyrosine phosphatase (PTP), can either positively
      or negatively regulate Src-family protein tyrosine kinase (PTK) activity in vivo.
      It is proposed that TCR-initiated signaling requires the segregation of PTP
      activities from the engaged TCR, based upon the differential membrane
      compartmentalization on the T cell surface. To test the importance of CD45
      exclusion from lipid microdomains for proper TCR signaling, a chimeric molecule
      was generated by fusing the CD45 cytoplasmic region, which contains the PTP
      domains, to the amino-terminal 12 amino acids of Lck, which target Lck to lipid
      microdomains. Using 3A9 T lymphocyte hybridoma (3A9H) cells whose TCR recognizes
      hen egg-white lysozyme (HEL), Lck-CD45 expression resulted in its targeting to
      lipid microdomains. The 3A9H cells expressing Lck-CD45 were reduced in their
      responses to HEL or co-cross-linking of CD3 and CD4, as assessed by IL-2
      production and Ca(2+) mobilization. Src-family PTK activity associated with lipid
      microdomains was also decreased. These results suggest that the segregation of
      CD45 from proximal TCR signaling components is necessary for TCR signaling and
      that the targeting of CD45 PTP activity to lipid microdomains on the T cell
      surface results in decreased sensitivity of TCR-mediated signaling.

PMID- 12207343
TI  - Tolerance induction to self antigens by peripheral dendritic cells.
AB  - It has been suggested, but not formally demonstrated, that peripheral dendritic
      cells (DC) alone are capable of tolerance induction by clonal deletion and/or
      anergy. To resolve such an issue, it is important to develop in vivo systems
      where DC are the only cells capable of presenting antigen and where a T cell
      population with a known antigen specificity can be followed. Here we use a
      transgenic murine model, which expresses the influenza virus hemagglutinin (HA)
      on B cells and on CD8alpha(+) and CD8alpha(-) DC but not on macrophages. If these
      mice are on a RAG(-/-) background, one has a model in which only DC present the
      HA antigen. In these mice, HA-specific T cells are deleted very efficiently in
      the thymus and those remaining in the periphery cannot respond to further
      antigenic stimulation in vitro and cannot eliminate antigen in vivo. By
      performing adoptive transfers, we show for the first time that self-antigen
      presentation exclusively by peripheral DC results in very efficient clonal
      deletion of the majority of antigen-specific T cells with the remaining ones in
      an anergic state. This model will permit us to further address the mechanisms by
      which DC tolerize or prime T cells and to investigate whether anergy induction by
      DC is similar to anergy induction by B cells.

PMID- 12207344
TI  - Uveitis in horses induced by interphotoreceptor retinoid-binding protein is
      similar to the spontaneous disease.
AB  - Equine recurrent uveitis (ERU) is an inflammatory eye disease with high
      similarity to uveitis in man. It is the only spontaneous animal model for uveitis
      and the most frequent eye disease in horses affecting up to 10% of the
      population. To further investigate the pathophysiology of ERU we now report the
      establishment of an inducible uveitis model in horses. An ERU-like disease was
      elicited in seven out of seven horses by injection of interphotoreceptor retinoid
      binding protein (IRBP) in complete Freund's adjuvant. Control horses did not
      develop uveitis. The disease model is characterized by a highly reproducible
      disease course and recurrent episodes with an identical time course elicited in
      all horses by repeated IRBP injections. The histology revealed the formation of
      lymphoid follicle-like structures in the eyes and an intraocular infiltration
      dominated by CD3(+) lymphocytes, morphological patterns typical for the
      spontaneous disease. Antigen-specific T cell proliferation of PBL was monitored
      prior to clinical uveitis and during disease episodes. An initial T cell response
      to IRBP-derived peptides was followed by epitope spreading to S-antigen-derived
      peptides in response to subsequent immunizations. Thus, horse experimental
      uveitis represents a valuable disease model for comparative studies with the
      spontaneous disease and the investigation of immunomodulatory therapeutic
      approaches after onset of the disease.

PMID- 12207345
TI  - Glycosylphosphatidylinositol-linked proteins are required for maintenance of a
      normal peripheral lymphoid compartment but not for lymphocyte development.
AB  - Surface proteins tethered to the membrane through a glycosylphosphatidylinositol
      (GPI) anchor are deficient in the blood cells of patients with paroxysmal
      nocturnal hemoglobinuria (PNH) as result of a somatic mutation, in a
      hematopoietic stem cell, of the X-linked phosphatidylinositolglycan
      complementation group A (PIG-A) gene. In PNH patients, compared to the large
      numbers of GPI-deficient myeloid cells, the proportion of GPI-deficient
      lymphocytes tends to be low, and therefore the impact of GPI deficiency on immune
      function has been unclear. We have obtained complementation by Pig-a(-) embryonic
      stem (ES) cells of Rag(-/-) blastocysts, and we show that Pig-a(-) ES cells are
      able to reconstitute the T cell and B cell compartments of Rag(-/-) mice.
      Although these mice were immunologically competent, by comparison with
      appropriate controls we detected several abnormalities: (1) increased levels of
      IgG; (2) high frequency/titers of anti-nuclear antibodies; (3) markedly reduced
      delayed hypersensitivity; and (4) impaired activation-induced lymphocyte death in
      vitro. In some cases, aging Pig-a(-)/Rag(-/-) chimeric mice developed
      lymphadenopathy and polyclonal T cell and B cell expansion. Thus, GPI-linked
      proteins are not required for lymphocyte development but they are required for
      normal lymphocyte function and for maintaining normal peripheral lymphoid
      homeostasis.

PMID- 12207346
TI  - CpG oligodeoxynucleotides induce human monocytes to mature into functional
      dendritic cells.
AB  - Dendritic cells (DC) excel at presenting antigen to T cells and thus make a key
      contribution to the induction of primary and secondary immune responses. DC
      matured in vitro and pulsed with antigen show promise for the immunotherapy of
      cancer and infectious diseases. Synthetic oligonucleotides (ODN) expressing
      immunomodulatory "CpG motifs" were found to boost APC function in mice. Current
      results demonstrate that the recently identified "D" type of CpG ODN stimulate
      human peripheral blood monocytes to mature into functionally active DC over 2-4
      days. The transition from monocyte to DC is characterized by the up-regulation of
      CD83, CD86, CD80, CD40 and the down-regulation of CD14. These DC support antigen
      specific humoral and cellular responses in vitro and in vivo. The differentiation
      of these monocytes is mediated by plasmacytoid DC, which respond to D type ODN by
      secreting IFN-alpha. Since D type CpG motifs are present in bacterial and viral
      DNA, the maturation of monocytes into functional DC may reflect a physiologic
      response that can be harnessed therapeutically through the use of CpG ODN.

PMID- 12207347
TI  - A role for membrane IgD in the tolerance of pathological human rheumatoid factor
      B cells.
AB  - Under non-autoimmune conditions, rheumatoid factor (RF) B cells coexist
      peacefully with their antigen (IgG), or can be transiently activated during
      secondary immune responses because they can present xenoantigens to specific T
      cells captured in immune complex form. Such a situation should lead to affinity
      maturation of RF B cells and potentially dangerous production of high-affinity
      RF. We used two lines of transgenic mice expressing a somatically mutated
      pathological human RF in presence (IgM and IgD) or in absence (IgM only) of
      surface IgD, and confirm that RF B cell tolerance can result from an antigen
      induced specific, but incomplete, deletion of naive RF B cells after antigen
      encounter. This deletion mainly concerns immature, transitional B cells. On the
      contrary, mature, IgM- and IgD-expressing RF B cells are resistant to such a
      deletion. These IgM and IgD RF B cells are functional and activable through both
      B cell receptor dependent (anti-IgM) and independent (LPS) pathways, but they are
      not fully responsive to human IgG either in vivo or in vitro. Taken together,
      these results suggest that another mechanism could be involved in the silencing
      of mature naive IgM and IgD RF B cells.

PMID- 12207348
TI  - Enhanced production of IL-18 in butyrate-treated intestinal epithelium by
      stimulation of the proximal promoter region.
AB  - Expression of IL-18 in intestinal epithelial cells (IEC) has been implicated in
      Th1 cell-mediated chronic intestinal inflammation and anti-tumor immunity.
      However, physiological regulatory factors have not been identified. Besides their
      effects on proliferation and restitution, immunomodulatory functions have been
      attributed to short chain fatty acids (SCFA). We investigated the effect of SCFA
      (butyrate, propionate, acetate) on expression of IL-18 in IEC in vitro and in
      vivo. Expression of IL-18 mRNA and protein in human carcinoma-derived HT-29 and
      Caco-2 cells was analyzed by reverse transcription-PCR and Western blot.
      Transcriptional regulation of IL-18 gene expression was determined by transient
      transfection of wild-type and mutated IL-18 promoter. Further, in vivo expression
      of IL-18 in the intestine from butyrate-treated and untreated mice was assessed
      by immunohistochemistry. IL-18 mRNA and the IL-18 protein were expressed in IEC,
      while IL-18 secretion was not observed. Butyrate and acetate increased
      intracellular IL-18 content in a time- and dose-dependent fashion. In contrast to
      proinflammatory stimuli butyrate potently activated the IL-18 promoter,
      indicating that IL-18 is regulated at the transcriptional level by SCFA.
      Furthermore, a 108-bp sequence in the proximal region was identified to be
      essential for IL-18 promoter activation by butyrate. As proof of principle
      butyrate effects were confirmed in vivo by demonstration of increased IL-18
      protein expression in IEC from butyrate-treated mice. In conclusion, SCFA up
      regulate IL-18 protein expression in IEC, suggesting a potential regulatory
      contribution of these luminal constituents to T cell mediated inflammatory and
      neoplastic intestinal conditions.

PMID- 12207349
TI  - Impact of antigen expression kinetics on the effectiveness of HIV-specific
      cytotoxic T lymphocytes.
AB  - Recent studies indicate that the time required for virus-infected cells to become
      vulnerable for the activity of CTL is of significance for the capacity of CTL to
      control ongoing viral reproduction. To investigate whether this applies to the
      effectiveness of HIV-1-specific CTL, we measured virus production in cultures
      containing CD4(+) T cells inoculated with HIV at low multiplicity of infection,
      and CTL directed against an early protein, Rev, or a late protein, RT. The Rev
      specific CTL prevented at least 2 log(10) more HIV-1 production, in 10 days, than
      similar numbers of RT-specific CTL. To study how CTL effectiveness depends on
      variations in the potency of effector functions and kinetics of HIV protein
      expression, we developed a mathematical model describing CTL-target cell
      interactions during successive infection cycles. The results show that
      substantially higher CTL-mediated target cell elimination rates are required to
      achieve control as there is less time for CTL to act before infected cells
      release progeny virions. Furthermore, in vitro experiments with HIV recombinant
      viruses showed that the RT-specific CTL were at least as effective as the Rev
      specific CTL, but only if the RT epitope was expressed as part of the early
      protein Nef. Together these results indicate that CTL control ongoing HIV
      reproduction more effectively if they are able to recognize infected cells
      earlier during individual viral replication cycles. This provides rationale for
      immunization strategies that aim at inducing, boosting or skewing CTL responses
      to early regulatory proteins in AIDS vaccine development.

PMID- 12207350
TI  - Massive inflammatory syndrome and lymphocytic immunodeficiency in KARAP/DAP12
      transgenic mice.
AB  - KARAP/DAP12 is a broadly distributed transmembrane signaling polypeptide with an
      immunoreceptor tyrosine-based activation motif, and is non-covalently associated
      with a variety of activating surface receptors. We report here the
      characterization of transgenic mice that overexpress KARAP/DAP12 polypeptides in
      both myeloid and lymphoid compartments. KARAP/DAP12-transgenic mice present, in a
      transgene dose-dependent manner, a complex phenotype characterized by two
      independent and spontaneous hematological abnormalities: (i) a severe lymphopenia
      and (ii) a massive inflammatory syndrome associated with neutrophilia and lung
      infiltration by multinucleated macrophages. These myeloid abnormalities observed
      in KARAP/DAP12-transgenic mice indicate that KARAP/DAP12-driven signals are
      critically involved in inflammation, and constitute an essential target to
      control the resolution of inflammatory disorders based on monocytes/macrophages
      and neutrophils.

PMID- 12207351
TI  - Processing of viable Salmonella typhimurium for presentation of a CD4 T cell
      epitope from the Salmonella invasion protein C (SipC).
AB  - We have identified Salmonella invasion protein C (SipC) as a target antigen for
      CD4 T cell recognition in mice infected with Salmonella typhimurium. SipC is a
      product of the type III secretion system encoded by S. typhimurium pathogenicity
      island 1. A SipC-specific T cell response was induced by infection with either
      the C5 wild type or attenuated SL3261 vaccine strain of S. typhimurium. We
      localized the response of T cell lines from infected mice to an epitope near the
      carboxyl terminus of SipC (SipC(381-394)) and studied the way it was processed
      from viable S. typhimurium. We demonstrated that CD4 T cell recognition of this
      epitope required actin-dependent uptake of S. typhimurium. Presentation also
      occurred when transport of newly synthesized MHC class II from the endoplasmic
      reticulum was disrupted and when the pH of intracellular compartments was raised,
      suggesting presentation by mature MHC class II recycled from the macrophage
      surface into neutral intracellular compartments. Salmonellae are known to
      colonize macrophages by localizing to compartments that do not make contact with
      the bactericidal environment of late endosomes or lysosomes, and thus might avoid
      lysosomal antigen processing. However, we demonstrate that a CD4 T cell response
      to S. typhimurium-secreted proteins may be induced by an alternative pathway
      capable of antigen presentation in conditions similar to those in the
      compartments where Salmonella localize.

PMID- 12207352
TI  - Anti-DNA autoreactivity in C4-deficient mice.
AB  - Mice lacking the classical complement component C4 (C4(-/-)) were evaluated for
      autoreactivity because classical complement deficiencies are major risk factors
      for human systemic lupus erythematosus (SLE). Naive, 6-month-old C4(-/-) mice
      have significantly more IgM anti-double-strand DNA antibodies than C4(+/+)
      controls. By 9 months, IgG anti-dsDNA antibodies are increased and this
      spontaneous autoreactivity is evident across a mixture of genetic backgrounds.
      C4(+/-) heterozygous mice also develop autoantibodies, reminiscent of the high
      incidence of partial C4 deficiency observed in human SLE. Kidneys of C4(-/-) mice
      have glomerular immune complexes, but progressive renal disease is not apparent
      in unmanipulated animals. Nonetheless, splenic B cells from C4(-/-) and not
      C4(+/+) mice as young as 3 months can be triggered to secrete IgM anti-dsDNA
      antibodies in vitro, before autoantibody titers are significantly elevated in
      vivo. These findings suggest that C4 normally helps prevent early stages of
      autoimmune disease and that C4 deficiency predisposes to abnormal regulation of
      autoreactive B cells.

PMID- 12207353
TI  - ICOS and CD28 reversely regulate IL-10 on re-activation of human effector T cells
      with mature dendritic cells.
AB  - With newly generated ICOS-ligand (ICOS-L)-specific monoclonal antibodies we
      determined that human Langerhans cells in situ express similar levels of ICOS-L,
      CD80, and CD86, compared to immature dendritic cells (DC) derived from monocytes
      in vitro. Maturation of DC strongly up-regulated CD80 and CD86 but did not
      significantly change ICOS-L levels. On coculture of "naive"CD4(+) T cells with
      mature DC in the presence of superantigen, ICOS was highly up-regulated on T
      cells, but played only a secondary role in the CD28-dominated release of TNF
      alpha and IFN-gamma, and did not participate in the induction of IL-2. Cocultures
      of "effector" CD4(+) T cells with mature DC revealed CD28 as the driving force
      for the secretion of IL-2, IFN-gamma, IL-6, and IL-13, with no apparent
      contribution of ICOS. In contrast, the release of IL-10 was differentially
      regulated. Interaction of ICOS with ICOS-L strongly promoted IL-10 secretion,
      whereas the CD28/B7 pathway acted as a potent attenuator of IL-10 release. Our
      data thus indicate a selective regulation of IL-10 secretion by ICOS on re
      activation of effector T cells with professional antigen-presenting cells
      (bearing CD80 and CD86) in lymphoid tissue.

PMID- 12207354
TI  - Genetic background determines the requirement for B7 costimulation in induction
      of autoimmunity.
AB  - B7 costimulatory molecules play an important role in inducing autoimmunity, tumor
      immunity, and transplant rejection, and therapeutic manipulation of B7 is being
      investigated in human diseases. To determine whether B7 costimulation is
      essential for inducing autoimmunity on different genetic backgrounds, we
      backcrossed B7.1/B7.2 deficient ((-/-)) mice on to the C57BL/6 (B6) and SJL
      backgrounds and induced experimental autoimmune encephalomyelitis (EAE) in these
      mice. B7.1/B7.2(-/-) mice on the B6 background were resistant to EAE induced with
      MOG 35-55, whereas the SJL B7.1/B7.2(-/-) mice were susceptible to PLP 139-151 or
      PLP 178-191-induced EAE. The SJL B7.1/B7.2(-/-) mice had a qualitatively
      different lesion pattern in that they showed increased white matter vacuolation
      compared to wild-type SJL mice when immunized with either PLP 139-151 or PLP 178
      191. (B6xSJL)F1 B7.1/B7.2(+/+) mice were susceptible to EAE whereas (B6xSJL)F1
      B7.1/B7.2(-/-) mice were resistant to EAE induced with either encephalitogenic
      peptide. Thus, genetic background determines the B7 requirement for inducing
      autoimmunity. These data have important implications for developing B7-based
      immunotherapies for human diseases.

PMID- 12207355
TI  - The fate of duplicated major histocompatibility complex class Ia genes in a
      dodecaploid amphibian, Xenopus ruwenzoriensis.
AB  - The dodecaploid anuran amphibian Xenopus ruwenzoriensis represents the only
      polyploid species of Xenopus in which the full silencing of the extra copies of
      the major histocompatibility complex (MHC) has not occurred. Xenopus
      ruwenzoriensis is a recent polyploid that has evolved within one of the two
      tetraploid groups of Xenopus through allopolyploidization. Family studies of its
      MHC haplotype suggested a polysomic inheritance of the MHC class I and II genes.
      Four class Ia bands can be detected per individual in Southern blot analysis and,
      similarly, four different cDNA sequences are expressed per individual. The
      Xenopus class Ia sequences we analyzed belong to only one of the old class I
      lineages and show a homogenization of their alpha3 domain sequences. This
      homogenization occurred after speciation within the Xenopus ruwenzoriensis
      species, either due to gene conversion or inter-alleles/loci recombination.A re
      evaluation of the polymorphism of class Ia in Xenopus, by looking at the rate of
      non-synonymous versus synonymous substitutions, suggests that Xenopus MHC class
      Ia genes are not under strong overdominant selection. This is a rare situation
      among vertebrates. The observed polymorphism is most likely due to the interlocus
      genetic exchanges related to the peculiar mode of speciation of the genus.

PMID- 12207357
TI  - Mechanistic investigation of the interaction between bisquaternary antimicrobial
      agents and phospholipids by liquid secondary ion mass spectrometry and
      differential scanning calorimetry.
AB  - Mechanisms of interaction between the antimicrobial drugs decamethoxinum and
      aethonium, which are based on bisquaternary ammonium compounds, and a
      phospholipid component of biological membranes, dipalmitoylphosphatidylcholine,
      were studied by means of liquid secondary ion mass spectrometry (LSIMS) and
      differential scanning calorimetry (DSC). Supramolecular complexes of the drugs
      with this phospholipid were recorded under secondary ion mass spectrometric
      conditions. The dependence of the structures of these complexes on structural
      parameters of the dications of the bisquaternary ammonium compounds was
      demonstrated. Tandem mass spectrometric investigations of the metastable decay of
      doubly charged ions of decamethoxinum and aethonium complexes with
      dipalmitoylphosphatidylcholine allowed estimation of structural parameters of
      these complexes in the gas phase. Interactions of decamethoxinum and aethonium
      with model membrane assemblies built from hydrated dipalmitoylphosphatidylcholine
      were studied using DSC. It was shown that while both drugs can interact with
      model membranes, the mechanisms of such interactions for decamethoxinum and
      aethonium differ. The correlation between the nature of these interactions and
      structural and electronic parameters of the dications of the two bisquaternary
      agents is discussed. Interpretation of combined mass spectrometric and
      calorimetric experimental data led to proposals that the molecular mechanisms of
      antimicrobial action of bisquaternary ammonium compounds are related to their
      effect on the membrane phospholipid components of microbial cells.

PMID- 12207358
TI  - Use of matrix clusters and trypsin autolysis fragments as mass calibrants in
      matrix-assisted laser desorption/ionization time-of-flight mass spectrometry.
AB  - Trypsin autolysis fragments and matrix clusters are often observed as intense
      peaks in mass spectra of protein digests. It is demonstrated that these can be
      exploited to improve the mass calibration of a matrix-assisted laser
      desorption/ionization time-of-flight (MALDI-TOF) spectrometer. Interpretation of
      some of the autolysis masses is complicated by the existence of disulfide bonds.
      Surprisingly large matrix clusters are often visible for alpha-cyano-4-hydroxy
      cinnamic acid. The fractional part of their masses differentiates them from
      protein digestion fragments.

PMID- 12207359
TI  - Advantages and drawbacks of nanospray for studying noncovalent protein-DNA
      complexes by mass spectrometry.
AB  - The noncovalent complexes between the BlaI protein dimer (wild-type and GM2
      mutant) and its double-stranded DNA operator were studied by nanospray mass
      spectrometry and tandem mass spectrometry (MS/MS). Reproducibility problems in
      the nanospray single-stage mass spectra are emphasized. The relative intensities
      depend greatly on the shape of the capillary tip and on the capillary-cone
      distance. This results in difficulties in assessing the relative stabilities of
      the complexes simply from MS(1) spectra of protein-DNA mixtures. Competition
      experiments using MS/MS are a better approach to determine relative binding
      affinities. A competition between histidine-tagged BlaIWT (BlaIWTHis) and the GM2
      mutant revealed that the two proteins have similar affinities for the DNA
      operator, and that they co-dimerize to form heterocomplexes. The low sample
      consumption of nanospray allows MS/MS spectra to be recorded at different
      collision energies for different charge states with 1 microL of sample. The MS/MS
      experiments on the dimers reveal that the GM2 dimer is more kinetically stable in
      the gas phase than the wild-type dimer. The MS/MS experiments on the complexes
      shows that the two proteins require the same collision energy to dissociate from
      the complex. This indicates that the rate-limiting step in the monomer loss from
      the protein-DNA complex arises from the breaking of the protein-DNA interface
      rather than the protein-protein interface. The dissociation of the protein-DNA
      complex proceeds by the loss of a highly charged monomer (carrying about two
      thirds of the total charge and one-third of the total mass). MS/MS experiments on
      a heterocomplex also show that the two proteins BlaIWTHis and BlaIGM2 have
      slightly different charge distributions in the fragments. This emphasizes the
      need for better understanding the dissociation mechanisms of biomolecular
      complexes.

PMID- 12207360
TI  - Triplex and quadruplex DNA structures studied by electrospray mass spectrometry.
AB  - DNA triplex and quadruplex structures have been successfully detected by
      electrospray ionization mass spectrometry (ESI-MS). Circular dichroism and UV
      melting experiments show that these structures are stable in 150 mM ammonium
      acetate at pH 7 for the quadruplexes and pH 5.5 for the triplexes. The studied
      quadruplexes were the tetramer [d(TGGGGT)](4), the dimer [d(GGGGTTTTGGGG)](2),
      and the intramolecular folded strand dGGG(TTAGGG)(3), which is an analog of the
      human telomeric sequence. The absence of sodium contamination allowed
      demonstration of the specific inclusion of n - 1 ammonium cations in the
      quadruplex structures, where n is the number of consecutive G-tetrads. We also
      detected the complexes between the quadruplexes and the quadruplex-specific drug
      mesoporphyrin IX. MS/MS spectra of [d(TGGGGT)](4) and the complex with the drug
      are also reported. As the drug does not displace the ammonium cations, one can
      conclude that the drug binds at the exterior of the tetrads, and not between
      them. For the triplex structure the ESI-MS spectra show the detection of the
      specific triplex, at m/z values typically higher than those typically observed
      for duplex species. Upon MS/MS the antigene strand, which is bound into the major
      groove of the duplex, separates from the triplex. This is the same dissociation
      pathway as in solution. To our knowledge this is the first report of a triplex
      DNA structure by electrospray mass spectrometry.

PMID- 12207361
TI  - Atmospheric pressure laser desorption/ionization on porous silicon.
AB  - A recently developed commercial atmospheric pressure matrix-assisted laser
      desorption/ionization (AP-MALDI) source (MassTech, Inc.) was modified to adopt
      commercially available DIOS plates (Mass Consortium Corp.) for the studies of
      laser desorption from the surface of porous silicon under atmospheric pressure
      conditions. The feasibility of atmospheric pressure laser desorption/ionization
      from the surface of porous silicon (AP-DIOS) was demonstrated. The advantages of
      this new AP-DIOS technique include reasonably good sensitivity (subpicomole range
      for standard peptide mixtures), simplicity of sample preparation, uniformity of
      target spots and the absence of matrix peaks in the spectra. The AP-DIOS source
      was interfaced with a commercial ion trap (LCQ Classic, Thermo Finnigan) which
      additionally provides a unique MS(n) capability. The AP-DIOS spectrum of 250 fmol
      of unseparated tryptic digest of bovine serum albumin (BSA) was compared with
      that of AP-MALDI for the same compound. AP-DIOS offers significantly better
      coverage for the digest components in the mass range 200-1000 Da. The combined
      data of both techniques enabled us to nearly double the number of matched peaks
      in BSA digest analysis compared with AP-DIOS or AP-MALDI analysis separately.

PMID- 12207362
TI  - Automated structural assignment of derivatized complex N-linked oligosaccharides
      from tandem mass spectra.
AB  - Glycoprotein function is controlled by several biological factors, one of them
      being the structure of carbohydrate chains (glycans) attached to specific amino
      acids of the protein backbone. Changes in glycan structures have been shown to
      modify the secondary and tertiary conformation of glycoproteins, thus their
      function. Powerful analytical tools are available for the characterization of
      sugar structures, and recently mass spectrometry (MS) has been increasingly
      useful for this purpose. Manual interpretation of tandem mass spectrum is
      possible but tedious. Automated interpretation should speed the analysis and
      enhance the results obtained. A new computer program for automated interpretation
      of tandem MS spectra of complex N-linked glycans oligosaccharides from mammals
      will be described. N-Linked oligosaccharides standards were derivatized with 1
      phenyl-3-methyl-5-pyrazolone (PMP) and analyzed by matrix-assisted laser
      desorption/ionization (MALDI)-tandem MS. Simulated tandem mass spectra of other
      common glycans were also generated to test the algorithm. The MALDI-MS/MS spectra
      featured resolved isotopic distributions for the [M + H](+) and fragment ions of
      oligosaccharides. These isotopic distributions complicated the automated analysis
      of the spectra and were removed to leave only monoisotopic peaks. An algorithm
      was written for this purpose, yielding simplified tandem mass spectra. Another
      algorithm is then used to determine the structure of the oligosaccharide. A score
      is then given to each structure, depending on agreement with experimental
      results. The program successfully assigned the true structure in 24 out of the 28
      cases (86%) and the true structure was among the three top scoring structures in
      all cases.

PMID- 12207363
TI  - Quantitative detection of salmeterol after inhalation in equine urine by liquid
      chromatography/tandem mass spectrometry.
AB  - A sensitive, accurate and precise liquid chromatography/tandem mass spectrometry
      (LC/MS(2)) method was developed for the quantification of salmeterol in the urine
      of horses. The method consists of a liquid-liquid extraction with tert
      butylmethyl ether and isopropanol at pH 12 after enzymatic hydrolysis. The
      extracts are analysed using an LC/MS system equipped with an electrospray
      ionisation (ESI) probe. Method validation showed excellent linearity,
      specificity, accuracy, precision and intra-laboratory repeatability and
      reproducibility. The limit of quantitative detection was 0.25 ng/mL and the limit
      of detection was 0.125 ng/mL. The excretion profile was determined after
      administration of 500 microg salmeterol (Serevent) to four standard-bred mares
      via a metered dose inhaler (MDI) with an Equinehaler adapter. Salmeterol was
      detected from 1 h until 12 h post-administration. Maximum urinary concentrations
      varied between 2.3 and 14.9 ng/mL.

PMID- 12207364
TI  - Electron capture negative ion mass spectra of some typical matrix-assisted laser
      desorption/ionization matrices.
AB  - A series of seven typical matrix-assisted laser desorption/ionization (MALDI)
      matrices has been investigated by means of electron capture negative ion mass
      spectrometry (ECNI-MS). It has been shown that the most effective matrices form
      deprotonated negative ions predominantly in the low-energy region. Relative
      dissociative cross sections have been measured for all molecules under
      investigation. The relative integrated abundance of [M - H](-) ion formation in
      the series changes by four orders of magnitude. It has been shown that 2,5-DHB
      (gentisic acid), one of the most effective MALDI matrices, has maximal relative
      intensity of [M - H](-) formation at the energy approximately equal 0.8 eV. This
      result is in accordance with a finding of Frankevich and Zenobi [Book of
      Abstracts, Workshop-school "Mass spectrometry in chemical physics, bio-physics
      and environmental sciences", Zvenigorod, Russia, April, 25-26, 2002, p. 40] that
      a probable origin of negative ions in MALDI is the process of low-energy (0.5-1
      eV) dissociative electron capture by matrix molecules.

PMID- 12207365
TI  - Direct determination of alkyl phosphates in human urine by liquid
      chromatography/electrospray tandem mass spectrometry.
AB  - A novel and rapid procedure based on liquid chromatography/tandem mass
      spectrometry (LC/MS/MS) for the determination of dialkyl phosphates (metabolites
      of organophosphorus pesticides) in human urine has been developed. After addition
      of 40 mM tetrabutylammonium acetate, 10 microL of urine sample were directly
      injected into the LC/MS/MS system. The method was validated yielding calibration
      curves with correlation coefficients greater than 0.997 and repeatability
      coefficient of variation (CV) lower than 9%. The accuracy and precision were
      evaluated by direct injection of spiked samples at 10 and 100 microg/L obtaining
      recoveries between 78 and 119% with coefficients of variation below 12%. Limits
      of detection of 1 microg/L for diethyl phosphate (DEP), diethylthiophosphate
      (DETP) and diethyldithiophosphate (DEDTP) and 2 microg/L for
      dimethyldithiophosphate (DMDTP) were achieved, all the analytes being detected in
      negative ion mode. The fragmentation pathway of dialkyl phosphates allowed us the
      use of an additional transition for confirmation in order to improve their
      identification in real-world samples. The applicability of the LC/MS/MS method
      was demonstrated by applying it to the analysis of urine samples of farmers
      exposed to the organophosphorus pesticide chlorpyrifos. Good correlation between
      application of the product in the field (citrus orchards), concentration levels
      of dialkyl phosphates and levels of the chlorpyrifos-specific metabolite (1,3,5
      trichloro-2-pyridinol) was obtained.

PMID- 12207366
TI  - Anomalous fractionation of sulfur isotopes during sputtering.
AB  - Secondary ion mass spectrometric (SIMS) measurements of sulfur isotope ratios
      obtained during sputtering with a Cs(+) beam and detection of negative secondary
      ions show a strong dependence of isotope fractionation on secondary ion energy
      for ions with approximately 2-10 eV excess kinetic energy (approximately 9 per
      thousand/eV), and a weak dependence for ions with approximately 10-approximately
      350 eV (0.05 per thousand/eV). Variable collection of the low-energy ions could
      thus result in variable measured sulfur isotope ratios. Being aware of this
      behavior should allow the analyst to avoid such a problem. The fractionation of
      the isotopes does not appear to follow theoretical or measured behavior for
      positive ions, and suggests that, at least for sulfur, the process of negative
      secondary ion emission is incompletely understood and may require different
      theoretical models.

PMID- 12207367
TI  - Electrospray ionization Fourier transform ion cyclotron resonance mass
      spectrometry to reveal the substrate specificity of the peptidyl-cysteine
      decarboxylase EpiD.
AB  - The microbial flavoenzyme EpiD catalyzes the oxidative decarboxylation of
      peptidyl-cysteines to peptidyl-aminoenethiols. These unusual C-terminally
      modified peptides are intermediates in the biosynthesis of the tetracyclic
      peptide antibiotic epidermin, which belongs to the lantibiotics family. The
      peptide SFNSYCC represents the C-terminal partial sequence of the natural
      precursor peptide EpiA. EpiA is posttranslationally modified to form finally the
      lantibiotic epidermin. The substrate specificity of EpiD was investigated using
      high-resolution mass spectrometry and the heptapeptide library SFNSXCC. The
      enzymatic conversion of particular peptides can be observed by a mass loss of m/z
      46. In contrast to the previously used triple quadrupole instrument, electrospray
      ionization Fourier transform ion cyclotron resonance mass spectrometry (ESI-FTICR
      MS) was able to resolve and detect all precursor and converted peptides with
      identical nominal masses in a single measurement, avoiding the necessity to
      investigate single peptides. Furthermore, a new substrate SFNSCCC of the enzyme
      EpiD was detected within the reaction mixture.

PMID- 12207368
TI  - Generic serial and parallel on-line direct-injection using turbulent flow liquid
      chromatography/tandem mass spectrometry.
AB  - The development of turbulent flow chromatography (TFC) has enabled considerable
      growth in the utility of on-line direct-injection technologies. TFC has now
      become established in a large number of varied analytical environments,
      particularly drug discovery/pharmacokinetics, metabolite profiling, combinatorial
      library purification, pre-clinical and clinical GLP applications. The utility of
      turbulent flow technology for in-house pre-clinical and clinical quantitative
      applications has necessitated extensive valve-cleaning procedures, and
      consequently lengthy cycle-times, to effectively remove the system carry-over. In
      house requirements for assay validation require carry-over less than 20% of the
      lowest level of quantification (LLOQ), corresponding to 0.02% carry-over for a
      linear calibration range incorporating 3 orders. A generic turbulent flow
      chromatography protocol has been developed for drug discovery that incorporates
      polymeric turbulent flow extraction (cyclone) with C18-based reverse-phase
      chromatography. Further, multiple wash steps are incorporated within the
      methodology to meet in-house requirements for carry-over. Selection of novel
      switching-valve materials based on polyarylethyl ketone (PAEK) and
      Hastelloy/Valcon E autosampler injection hardware has enabled us to significantly
      impact the cycle-time required to reduce carry-over. Consequently, optimal usage
      of switching valves has enabled parallel operation for a generic on-line direct
      injection methodology to successfully reduce the total cycle-time. Overall
      reductions from 4 min per sample to 90 s per sample are shown with comparable
      data quality using a proprietary target molecule from 0.1-100 ng/mL. This paper
      describes the hardware configuration and methodologies utilized to perform
      generic serial and parallel on-line direct-injection using a Turboflow HTLC 2300
      system.

PMID- 12207369
TI  - Identification of N-terminal acetylation in Hb Raleigh (beta1Val-->Ac-Ala) by
      electrospray tandem mass spectrometry.

PMID- 12207374
TI  - Solid-state NMR spectroscopic methods in chemistry.
AB  - Over the last decades, NMR spectroscopy has grown into an indispensable tool for
      chemical analysis, structure determination, and the study of dynamics in organic,
      inorganic, and biological systems. It is commonly used for a wide range of
      applications from the characterization of synthetic products to the study of
      molecular structures of systems such as catalysts, polymers, and proteins.
      Although most NMR experiments are performed on liquid-state samples, solid-state
      NMR is rapidly emerging as a powerful method for the study of solid samples and
      materials. This Review outlines some of the developments of solid-state NMR
      spectroscopy, including techniques such as cross-polarization, magic-angle
      spinning, multiple-pulse sequences, homo- and heteronuclear decoupling and
      recoupling techniques, multiple-quantum spectroscopy, and dynamic angle spinning,
      as well as their applications to structure determination. Modern solid-state NMR
      spectroscopic techniques not only produce spectra with a resolution close to that
      of liquid-state spectra, but also capitalize on anisotropic interactions, which
      are often unavailable for liquid samples. With this background, the future of
      solid-state NMR spectroscopy in chemistry appears to be promising, indeed.

PMID- 12207375
TI  - Biological and medical significance of calcium phosphates.
AB  - The inorganic part of hard tissues (bones and teeth) of mammals consists of
      calcium phosphate, mainly of apatitic structure. Similarly, most undesired
      calcifications (i.e. those appearing as a result of various diseases) of mammals
      also contain calcium phosphate. For example, atherosclerosis results in blood
      vessel blockage caused by a solid composite of cholesterol with calcium
      phosphate. Dental caries result in a replacement of less soluble and hard apatite
      by more soluble and softer calcium hydrogenphosphates. Osteoporosis is a
      demineralization of bone. Therefore, from a chemical point of view, processes of
      normal (bone and teeth formation and growth) and pathological (atherosclerosis
      and dental calculus) calcifications are just an in vivo crystallization of
      calcium phosphate. Similarly, dental caries and osteoporosis can be considered to
      be in vivo dissolution of calcium phosphates. On the other hand, because of the
      chemical similarity with biological calcified tissues, all calcium phosphates are
      remarkably biocompatible. This property is widely used in medicine for
      biomaterials that are either entirely made of or coated with calcium phosphate.
      For example, self-setting bone cements made of calcium phosphates are helpful in
      bone repair and titanium substitutes covered with a surface layer of calcium
      phosphates are used for hip-joint endoprostheses and tooth substitutes, to
      facilitate the growth of bone and thereby raise the mechanical stability. Calcium
      phosphates have a great biological and medical significance and in this review we
      give an overview of the current knowledge in this subject.

PMID- 12207376
TI  - Asymmetric photochemistry and photochirogenesis.
AB  - One of the most interesting phenomena on Earth is the chirality of biomolecules,
      the origin of which remains unknown. A challenge arising from this phenomenon is
      the selective, atom-economic synthesis of enantiomerically pure target molecules
      from nonchiral starting materials. Herein, new developments in the field of
      asymmetric photochemistry and photochirogenesis are described with special
      emphasis on absolute asymmetric synthesis. In this context, the elucidation of
      the ultimate cause of homochirality phenomena on earth and the possible
      correlation with physicochemical parameters are also presented.

PMID- 12207377
TI  - The scientific and humane legacy of Max Perutz (1914-2002).

PMID- 12207378
TI  - Biomineralization in diatoms mediated through peptide- and polyamine-assisted
      condensation of silica.

PMID- 12207379
TI  - Formal vinyl C[bond]H activation and allylic oxidation by olefin metathesis.

PMID- 12207380
TI  - An enantiomerically pure propeller-shaped supramolecular capsule based on the
      stereospecific self-assembly of two chiral tris(oxazoline) ligands around three
      Ag(I) ions.

PMID- 12207381
TI  - Deracemization of alpha-methylbenzylamine using an enzyme obtained by in vitro
      evolution.

PMID- 12207382
TI  - Fabrication of carbohydrate chips for studying protein-carbohydrate interactions.

PMID- 12207383
TI  - Vapor-induced luminescence switching in crystals of the syn isomer of a dinuclear
      (bipyridine)platinum(II) complex bridged with pyridine-2-thiolate ions.

PMID- 12207384
TI  - Ruthenium photocatalysts capable of reversibly storing up to four electrons in a
      single acceptor ligand: a step closer to artificial photosynthesis.

PMID- 12207385
TI  - Remarkably stable tetrahedral intermediates: carbinols from nucleophilic
      additions to N-acylpyrroles.

PMID- 12207386
TI  - Total synthesis of (+)-epoxyquinols A and B.

PMID- 12207387
TI  - Novel glycodendrimers self-assemble to nanoparticles which function as polyvalent
      ligands in vitro and in vivo.

PMID- 12207388
TI  - Molecular composition of liquid sulfur.

PMID- 12207389
TI  - Towards a DNA-like duplex without hydrogen-bonded base pairs.

PMID- 12207390
TI  - Stereoselective synthesis of tri- and tetrasubstituted olefins by tandem
      cyclization addition reactions featuring vinyl radicals.

PMID- 12207391
TI  - Do isopropyl and tert-butyl cations form pi complexes with benzene?

PMID- 12207392
TI  - Activity of lipases and esterases towards tertiary alcohols: insights into
      structure-function relationships.

PMID- 12207393
TI  - (1)[HgGe(9)](2-)--a polymer with zintl ions as building blocks covalently linked
      by heteroatoms.

PMID- 12207394
TI  - A further step towards single-molecule sequencing: Escherichia coli exonuclease
      III degrades DNA that is fluorescently labeled at each base pair.

PMID- 12207395
TI  - Ligand design and bioconjugation of colloidal gold nanoparticles.

PMID- 12207396
TI  - Total syntheses and structures of angular [6]- and [7]phenylene: the first
      helical phenylenes (heliphenes).

PMID- 12207397
TI  - Total syntheses of angular [7]-, [8]-, and [9]phenylene by triple cobalt
      catalyzed cycloisomerization: remarkably flexible heliphenes.

PMID- 12207398
TI  - A New Pd(0)-Cu(I) bimetallic catalyst for the synthesis of indoles from
      isocyanates and allyl carbonates.

PMID- 12207399
TI  - Fluorescence enhancement through enzymatic cleavage of internally quenched
      dendritic peptides: a sensitive assay for the AspN endoproteinase.

PMID- 12207400
TI  - Layer-by-layer deposition and ordering of low-molecular-weight dye molecules for
      second-order nonlinear optics.

PMID- 12207401
TI  - An axially bridged indium phthalocyanine dimer with an IN[bond]IN bond.

PMID- 12207402
TI  - Samarium diiodide-mediated reductive coupling of epoxides and carbonyl compounds:
      a stereocontrolled synthesis of C-glycosides from 1,2-anhydro sugars.

PMID- 12207403
TI  - Addition of ureas to arynes: straightforward synthesis of benzodiazepine and
      benzodiazocine derivatives.

PMID- 12207405
TI  - Singlet delta oxygen production from a gas-solid reaction.

PMID- 12207404
TI  - Pyrazolate coordination continues to amaze--the new mu-eta(2):eta(1) binding mode
      and the first case of unidentate coordination to a rare earth metal.

PMID- 12207406
TI  - Controlled release of a dendritically encapsulated template molecule.

PMID- 12207407
TI  - Phosphite dehydrogenase: a versatile cofactor-regeneration enzyme.

PMID- 12207408
TI  - Guest preorganization: an alternative "bioinspired" paradigm in host-guest
      chemistry.

PMID- 12207409
TI  - A concise formal total synthesis of (+/-)-strychnine by using a transannular
      inverse-electron-demand Diels-Alder reaction of a
      [3](1,3)idolo[3](3,6)pyridazinophane.

PMID- 12207410
TI  - Sterically hindered lithium dialkylcuprates for the generation of highly
      functionalized mixed cuprates through a halogen-copper exchange.

PMID- 12207411
TI  - Tin-free radical-mediated C[bond]C-bond formations with alkyl allyl sulfones as
      radical precursors.

PMID- 12207412
TI  - Chirality induction through the reversible catenation of coordination rings.

PMID- 12207413
TI  - An alkynylboronic ester annulation: development of synthetic methods for
      application to diversity-oriented organic synthesis.

PMID- 12207414
TI  - The total synthesis of coleophomones B and C.

PMID- 12207415
TI  - A highly efficient and flexible synthesis of substituted carbazoles by rhodium
      catalyzed inter- and intramolecular alkyne cyclotrimerizations.

PMID- 12207416
TI  - Transannular radical cascade as an approach to the diastereoselective synthesis
      of linear triquinane.

PMID- 12207419
TI  - Estrogen plus progestin increased coronary heart disease and breast cancer events
      in postmenopausal women.

PMID- 12207420
TI  - Review: postmenopausal estrogen replacement therapy increases the risk for venous
      thromboembolism.

PMID- 12207422
TI  - Isotonic hydration reduced contrast media-associated nephropathy in elective or
      emergency coronary angioplasty.

PMID- 12207421
TI  - Primary percutaneous coronary intervention was more effective than thrombolytic
      therapy for acute MI.

PMID- 12207423
TI  - Planned angiography after percutaneous coronary intervention increased
      reinterventions but did not affect mortality or MI.

PMID- 12207424
TI  - Mild hypothermia improved neurologic outcome and reduced mortality after cardiac
      arrest because of ventricular arrhythmia.

PMID- 12207425
TI  - Warfarin combined with low-dose aspirin in MI did not provide clinical benefit
      beyond that of aspirin alone.

PMID- 12207426
TI  - Review: angiotensin-receptor blockers do not reduce mortality or hospitalization
      rates in heart failure.

PMID- 12207427
TI  - Review: n-3 polyunsaturated fatty acids reduce fatal MI, sudden death, and
      overall mortality in coronary heart disease.

PMID- 12207428
TI  - Review: noninvasive ventilation reduces mortality in acute respiratory failure.

PMID- 12207429
TI  - Review: albumin increases mortality in critically ill patients.

PMID- 12207430
TI  - Review: tricyclic antidepressants, capsaicin, gabapentin, and oxycodone are
      effective for postherpetic neuralgia.

PMID- 12207431
TI  - Review: selegiline improves symptoms and levodopa is better than pramipexole for
      motor function in untreated Parkinson disease.

PMID- 12207432
TI  - Review: proton-pump inhibitors alleviate symptoms of functional (nonulcer)
      dyspepsia but may not be better than H2-antagonists.

PMID- 12207433
TI  - A lifestyle intervention or metformin prevented or delayed the onset of type 2
      diabetes in persons at risk.

PMID- 12207434
TI  - Review: intensive insulin pump therapy slightly improves glycemic control in type
      1 diabetes.

PMID- 12207435
TI  - Review: home visiting with multidimensional assessment and multiple visits is
      effective in low-risk elderly persons.

PMID- 12207436
TI  - Review: brief interventions reduce drinking in patients not seeking treatment.

PMID- 12207437
TI  - A brief intervention reduced alcohol drinking for up to 48 months in problem
      drinkers.

PMID- 12207438
TI  - Review: interferon alpha-2b is effective for biochemical and virologic outcomes
      in acute hepatitis C virus infection.

PMID- 12207439
TI  - Review: Pygeum africanum extracts improve symptoms and urodynamics in symptomatic
      benign prostatic hyperplasia.

PMID- 12207440
TI  - A normal-calcium, low-protein, low-salt diet reduced recurrence of renal stones
      over 5 years.

PMID- 12207441
TI  - Review: inhaled corticosteroids for asthma or chronic obstructive pulmonary
      disease do not increase bone loss.

PMID- 12207442
TI  - Parental education and guided self-management of asthma or wheeze in preschool
      children were not effective.

PMID- 12207443
TI  - Physiotherapy or a wait-and-see policy was the best option for lateral
      epicondylitis at 1 year.

PMID- 12207444
TI  - Bed rest, physiotherapy, and continuation of activities of daily living were
      equally effective for sciatica.

PMID- 12207445
TI  - Review: antiemetic drugs reduce nausea in early pregnancy.

PMID- 12207446
TI  - Telephone-based peer support increased the duration of breast-feeding in
      primiparous mothers.

PMID- 12207447
TI  - Sertraline maintenance treatment reduced relapse and dropouts in posttraumatic
      stress disorder.

PMID- 12207448
TI  - Clonidine and methylphenidate were effective for attention deficit hyperactivity
      disorder in children with comorbid tics.

PMID- 12207449
TI  - Review: nedocromil sodium decreases airflow reduction and recovery time in
      exercise-induced bronchoconstriction.

PMID- 12207450
TI  - Review: beta2-agonists are ineffective but increase adverse effects in acute
      bronchitis without underlying pulmonary disease.

PMID- 12207451
TI  - Pharmacist review changed more repeat prescriptions for elderly patients than did
      usual general practice review.

PMID- 12207452
TI  - Review: questionnaires for detecting clinical depression in primary care have
      similar diagnostic accuracy.

PMID- 12207453
TI  - Patients who survived the first 30 days after a first episode of status
      epilepticus had increased mortality at 10 years.

PMID- 12207454
TI  - Elevated plasma total homocysteine levels increased the risk for dementia in the
      elderly.

PMID- 12207455
TI  - Review: in-hospital care pathways for acute stroke do not improve clinical
      outcomes and lower quality of life.

PMID- 12207456
TI  - Practice corner: using clinical prediction rules.

PMID- 12207457
TI  - Determination of carboxylic acids in vinegars and in Aceto Balsamico Tradizionale
      di Modena by HPLC and GC methods.
AB  - The presence of carboxylic acids in grape products has been investigated for a
      long time by researchers, from both the qualitative and quantitative points of
      view. Evaluation of carboxylic acids requires the study and optimization of some
      operative variables which are strictly related to the matrix. In particular, the
      determination of organic acids in real matrixes such as Aceto Balsamico
      Tradizionale of Modena (ABTM; a traditional balsamic vinegar made from cooked
      grape must) is often difficult because of the presence of numerous interferences
      that need to be removed by separation techniques. To this aim, in the present
      work a solid-phase extraction (SPE) method with C18 and NH(2) exchangers was used
      to clean the ABTM samples prior to analysis or further treatments. Both HPLC and
      GC techniques were used to determine organic acids. The efficiency of these two
      different analytical techniques in the study of ABTM acidic composition has been
      evaluated. Both methods separately were not able to supply all the data related
      to carboxylic acids. In particular, HPLC allows acetic and lactic acids
      quantification, but gluconic and succinic acids are better determined by GC. As
      far as tartaric, citric, and malic acids are concerned, both HPLC and GC methods
      give statistically equivalent results. The variation of the single acidic species
      composition along a series of casks furnished interesting information regarding
      the chemical transformations taking place during the aging process of this
      product.

PMID- 12207458
TI  - Beef- and bovine-derived material identification in processed and unprocessed
      food and feed by PCR amplification.
AB  - This research developed and evaluated a PCR procedure to detect beef in heated
      and unheated meat, sausages, and canned food, using a specific and sensitive
      method. To confirm the effectiveness and specificity of this fragment, we tested
      45 cattle blood DNA samples (from different breeds) and obtained positive
      results. With 125 samples tested from other species, the specific beef
      amplification was not detected. Feed components intended for cattle nutrition
      were also checked, and bovine-derived material was detected. Using this method we
      can detect the degree of contamination up to 0.01% raw beef in pork. In the same
      way, 1% beef was detected in cooked meat mixtures and bovine-derived material in
      concentrate mixtures. Beef has been identified in both heated and unheated meat
      products, sausages, canned food, and hamburgers. In conclusion, specific PCR
      amplification of a repetitive DNA element seems to be a powerful technique for
      the identification of beef in processed and unprocessed food, because of its
      simplicity, specificity and sensitivity. Furthermore, feed components intended
      for cattle nutrition can be checked. The procedure is also much cheaper than
      other methods based on RFLPs-PCR, immunodiffusion, and other techniques that need
      expensive equipment.

PMID- 12207459
TI  - Quantitative PCR detection of pork in raw and heated ground beef and pate.
AB  - Quantitative estimates are important to establish whether pork adulteration in
      ground beef and pate is accidental or intentional. A PCR procedure has been
      developed and evaluated to quantify pork in heated and nonheated meat and pates
      by densitometry using a specific and sensitive repetitive DNA element. Thirty,
      twenty-five, and twenty PCR cycles were carried out to find the best standard
      curve and correlation between pork content and band intensity. Twenty cycles
      showed the best results, quantifying degree contamination up to 1% pork in beef
      (heated and nonheated) and pork in duck pate with a minimum error. Finally, fraud
      was found in commercial pates.

PMID- 12207460
TI  - Solid phase extraction and liquid chromatography-tandem mass spectrometry for the
      evaluation of 4-hydroxy-2-nonenal in pork products.
AB  - This research was aimed at setting up an analytical method for the determination
      in pork products of 4-hydroxy-2-nonenal (4-HNE), an aldehyde produced from the
      oxidation of omega-6-polyunsaturated fatty acids. Such a compound mediates
      various biological effects, but it is considered to be very toxic to mammalian
      cells at levels higher than physiological ones. The methods used for the
      determination of 4-HNE in biological fluids, such as blood, were found to be
      unsuitable for meat samples because both the repeatability and the recovery in
      spiked samples were unsatisfactory. A new method, based on solid phase extraction
      and HPLC-MS/MS, was therefore developed and validated. The limit of detection of
      4-HNE in spiked samples was 0.043 mg/kg, and the recovery was approximately 60%
      depending on the concentration. Good linearity was observed in the range of 0.1
      10 mg/kg, and repeatability and interday and intraday precision expressed as
      relative standard deviation were <10%. The method has been successfully applied
      to the determination of the aldehyde in samples of various pork products. 4-HNE
      was present in some products, especially the smoked and/or cooked ones, at levels
      that might not be a real risk for human health.

PMID- 12207461
TI  - Development of an enzyme-linked immunosorbent assay for bisphenol a using chicken
      immunoglobulins.
AB  - Bisphenol A was coupled, after derivatization into a suitable hapten, to bovine
      serum albumin and ovalbumin in order to produce immunizing and coating antigens.
      The immunizing antigens were injected into chickens, which allowed the isolation
      of specific bisphenol A immunoglobulins from the egg yolk. These antibodies were
      used in an indirect competitive enzyme-linked immunosorbent assay for the
      determination of bisphenol A in aqueous solutions. Various parameters,
      influencing the assay sensitivity, were evaluated. The applicability of the assay
      for the determination of bisphenol A in milk was also studied. The assay was not
      as sensitive as other analytical techniques used in bisphenol A analysis, since
      typical I(50) levels of 2.5 microM were reached in aqueous solutions. This study
      nevertheless illustrates the usefulness and the potency of chicken antibodies in
      the analysis of migration residues from packaging materials using immunochemical
      techniques. In addition, the assay showed to be quite specific for bisphenol A as
      well. Only for bisphenol A analogues, cross reactivities of about 40% were
      reached, enabling the use of the antibodies for the screening of bisphenol A and
      alike compounds.

PMID- 12207462
TI  - Determination by near-infrared spectroscopy of perseitol used as a marker for the
      botanical origin of avocado (Persea americana Mill.) honey.
AB  - This paper reports the application of near-infrared (NIR) reflectance
      spectroscopy to determine the concentration in honey of perseitol, a sugar that
      is specific to avocado honey. Reference values for perseitol were obtained by
      high-performance liquid chromatography analysis in 109 honey samples. Although
      the average concentration of perseitol in honey samples was only 0.48%, accurate
      prediction equations were successfully developed. The regression model of
      modified partial least squares was superior to that of principal component
      regressions. Calibrations based on the first or second derivative of Log(1/R)
      were equally good (R(2) > 0.95). Using half of the samples for calibration and
      the second half for validation, the correlation between actual and predicted
      values of the second half was satisfactory (R(2) = 0.87), the slope did not
      differ from 1, bias was low (0.005%), and the standard error of prediction was
      relatively low (0.13%). It was concluded that NIRS analysis may be used to detect
      to what extent honeybees have harvested avocado nectar but not to authenticate
      avocado honey as unifloral.

PMID- 12207463
TI  - Sensitive micellar electrokinetic chromatography-laser-induced fluorescence
      method to analyze chiral amino acids in orange juices.
AB  - In this work a new method to detect the existence of chiral amino acids in orange
      juice is presented. The method employs beta-cyclodextrins and micellar
      electrokinetic chromatography with laser-induced fluorescence (MEKC-LIF) to
      separate and detect L- and D-amino acids (L-aa and D-aa) previously derivatized
      with fluorescein isothiocianate (FITC). A systematic optimization of the chiral
      MEKC conditions is done bringing about in less than 20 min a good separation of
      the main amino acids found in orange juice (i.e., Pro, Asp, Ser, Asn, Glu, Ala,
      Arg, and the nonchiral GABA, i.e., gamma-aminobutyric acid). Using this
      procedure, the analysis time reproducibility for the 15 standard compounds (L-aa,
      D-aa, and GABA) has been determined to be better than 0.2% (n = 5) for the same
      day and better than 0.7% (n = 15) for three different days. Corrected peak area
      reproducibility is somewhat lower, providing values better than 3.3% (n = 5) for
      the same day and 6.9% (n = 15) for three different days. The limit of detection
      using this procedure was determined to be 0.86 attomoles for L-Arg. The optimized
      FITC derivatization method allows the easy and straightforward detection of amino
      acids in orange concentrates and juices (i.e., only centrifugation of diluted
      samples for 5 min is needed prior to their derivatization). D-Ala, D-Asp, D-Arg,
      and D-Glu were determined in orange juices and orange concentrates from different
      geographical origins using this new method. Moreover, the effect of different
      temperature treatments (50, 92, and 150 degrees C) on the content of D-aa in
      orange juice was evaluated.

PMID- 12207464
TI  - Antioxidant activities and phenolic composition of extracts from Greek oregano,
      Greek sage, and summer savory.
AB  - Oregano vulgare L. ssp. hirtum (Greek oregano), Salvia fruticosa (Greek sage),
      and Satureja hortensis (summer savory) were examined as potential sources of
      phenolic antioxidant compounds. The antioxidant capacities (antiradical activity
      by DPPH* test, phosphatidylcholine liposome oxidation, Rancimat test) and total
      phenol content were determined in the ethanol and acetone extracts of the dried
      material obtained from the botanically characterized plants. The ground material
      was also tested by the Rancimat test for its effect on the stability of sunflower
      oil. The data indicated that ground material and both ethanol and acetone
      extracts had antioxidant activity. Chromatographic (TLC, RP-HPLC) and NMR
      procedures were employed to cross-validate the presence of antioxidants in
      ethanol and acetone extracts. The major component of all ethanol extracts was
      rosmarinic acid as determined by RP-HPLC and NMR. Chromatography indicated the
      presence of other phenolic antioxidants, mainly found in the acetone extracts.
      The presence of the flavones luteolin and apigenin and the flavonol quercetin was
      confirmed in the majority of the extracts by the use of a novel (1)H NMR
      procedure, which is based on the strongly deshielded OH protons in the region of
      12-13 ppm without previous chromatographic separation. This deshielding may be
      attributed to the strong intramolecular six-membered ring hydrogen bond of the
      OH(5)...CO(4) moiety.

PMID- 12207465
TI  - Steryl phenolic acid esters in cereals and their milling fractions.
AB  - The steryl ferulate contents of rye and wheat grains and their milling fractions
      were analyzed using a reversed-phase high-performance liquid chromatographic
      (HPLC) method. HPLC-mass spectrometry was used for identification. In addition,
      steryl ferulates of some selected milling byproducts were determined. The total
      steryl ferulate contents of rye and wheat grains were 6.0 and 6.3 mg/100 g,
      respectively. Uneven distribution of steryl ferulates in the grains led to
      considerable differences in the milling products; their steryl ferulate contents
      ranged from trace amounts in flours with low ash content to 20 and 34 mg/100 g in
      rye and wheat brans, respectively. Campestanyl ferulate and sitostanyl ferulate
      were the main components, followed by campesteryl ferulate and sitosteryl
      ferulate, whereas sitosterol was the main component in total sterols. Among the
      other samples, a byproduct of rice milling (pearling dust) was the best source of
      steryl ferulates, its total steryl ferulate content being 119 mg/100 g, whereas
      no measurable amounts of steryl ferulates were measured in oat bran or pearling
      dust of barley. The results indicated that rye and wheat and especially their
      bran fractions are comparable to corn as steryl ferulate sources.

PMID- 12207466
TI  - Inhibition of lipid peroxidation and structure-activity-related studies of the
      dietary constituents anthocyanins, anthocyanidins, and catechins.
AB  - The antioxidant activities of a series of commonly consumed and biogenetically
      related plant phenolics, namely, anthocyanidins, anthocyanins, and catechins, in
      a liposomal model system have been investigated. The antioxidant efficacies of
      the compounds were evaluated on their abilities to inhibit the fluorescence
      intensity decay of an extrinsic probe, 3-[p-(6-phenyl)-1,3,5
      hexatrienyl]phenylpropionic acid, caused by free radicals generated during metal
      ion-induced peroxidation. Distinct structure-activity relationships were revealed
      for the antioxidant abilities of these structurally related compounds. Whereas
      antioxidant activity increased with an increasing number of hydroxyl substituents
      present on the B-ring for anthocyanidins, the converse was observed for
      catechins. However, substitution by methoxyl groups diminished the antioxidant
      activity of the anthocyanidins. Substitution at position 3 of ring C played a
      major role in determining the antioxidant activity of these classes of compounds.
      The anthocyanidins, which possess a hydroxyl group at position 3, demonstrated
      potent antioxidant activities. For the cyanidins, an increasing number of
      glycosyl units at position 3 resulted in decreased antioxidant activity.
      Similarly, the substitution of a galloyl group at position 3 of the flavonoid
      moiety resulted in significantly decreased antioxidant activity for the
      catechins. Among catechins, cis-trans isomerism, epimerization, and racemization
      did not play a role in overall antioxidant activity. The antioxidant activities
      of test compounds (at 40 microM concentrations) were compared to the commercial
      antioxidants tert-butylhydroquinone, butylated hydroxytoluene, butylated
      hydroxyanisole, and vitamin E (all at 10 microM concentrations).

PMID- 12207467
TI  - Effect of glycosylation modification (N-Q-(108)I --> N-Q-(108)T) on the freezing
      stability of recombinant chicken Cystatin overexpressed in Pichia pastoris X-33.
AB  - The cDNAs encoding chicken cystatin and its N-glycosylation-modified mutant
      (Asn(106)-Ile(108)-->Asn(106)-Thr(108)) were cloned into the pGAPZ alpha C
      expression vector, using the GAP as promoter and Zeocin as resistant agent, and
      transformed into Pichia pastoris X-33 expression host. The effect of N
      glycosylation on the stability of recombinant chicken cystatin was investigated.
      A large quantity of recombinant chicken cystatin and the Asn(106)-glycosylated
      cystatins were expressed and secreted into broth using alpha-factor
      preprosequence. The K(i) of the recombinant chicken cystatin (0.08 nM) was
      similar to that of wild-type chicken cystatin (0.05 nM). They acted as a
      competitive inhibition reaction against papain. According to the K(i), the
      inhibition ability of Asn(106)-glycosylated mutant cystatin (K(i) = 9.5 nM) was
      weaker than that of the wild-type one. However, N-glycosylation at Asn(106)
      substantially enhanced the freezing stability of recombinant chicken cystatin
      overexpressed in P. pastoris.

PMID- 12207468
TI  - Effect of different forms of alkali treatment on specific fermentation inhibitors
      and on the fermentability of lignocellulose hydrolysates for production of fuel
      ethanol.
AB  - Treatment with alkali, particularly overliming, has been widely used as a method
      for the detoxification of lignocellulose hydrolysates prior to ethanolic
      fermentation. However, the mechanisms behind the detoxification effect and the
      influence of the choice of cation have not been well understood. In this study, a
      dilute acid hydrolysate of spruce and an inhibitor cocktail consisting of six
      known inhibitors were used to investigate different alkali detoxification
      methods. The various treatments included the addition of calcium hydroxide,
      sodium hydroxide, potassium hydroxide, and ammonia to pH 10.0 and subsequent
      adjustment of the pH to 5.5 with either sulfuric or hydrochloric acid as well as
      treatment with the corresponding amounts of calcium, sodium, and potassium as
      sulfate or chloride salts at pH 5.5. An RP-HPLC method was developed for the
      separation of 18 different inhibitors in the hydrolysate, including furaldehydes
      and phenolics. Detection and quantification were carried out by means of UV, DAD,
      and ESI-MS in negative mode. Treatment of the spruce hydrolysate with alkali
      resulted in up to approximately 40% decrease in the concentration of
      furaldehydes. The effects on the aromatic compounds were complex. Furthermore,
      SFE was performed on the precipitate formed during alkali treatment to evaluate
      the inhibitor content of the precipitate, and the following RP-HPLC analysis
      implied that potential inhibitors were removed mainly through conversion rather
      than through filtration of precipitate. Parallel experiments in which sulfuric
      acid or hydrochloric acid was used for acidification to pH 5.5 after alkali
      treatment indicated that the choice of anion did not affect the removal of
      inhibitors. Detoxification with calcium hydroxide and ammonia resulted in better
      fermentability using Saccharomyces cerevisiae than detoxification with sodium
      hydroxide. The results from the experiments with the inhibitor cocktail indicated
      that the positive effects of alkali treatment are difficult to explain by removal
      of the inhibitors only and that possible stimulatory effects on the fermenting
      organism warrant further attention.

PMID- 12207470
TI  - Effects of management on the yield and high-molecular-weight polysaccharide
      content of shiitake (Lentinula edodes) mushrooms.
AB  - Shiitake (Lentinula edodes (Berk.) Pegler) mushroom production in the United
      States has increased greatly over the last twenty years. Additional expansion of
      the shiitake mushroom market should be possible if the product can be marketed as
      a functional food, i.e., a food that has health-promoting effects beyond its
      nutritional value. High-molecular-weight polysaccharides (HMWP) including
      lentinan in shiitake may promote human health. This study was conducted to
      determine if management protocols influence the HMWP of shiitake mushrooms.
      Results indicate that measuring the total carbohydrate content of water
      extractable, ethanol-insoluble polysaccharides was a simple way to estimate HMWP.
      Results also indicate that log-grown shiitake contained more HMWP than did
      substrate-grown shiitake. Among log-grown shiitake, both mushroom strain and tree
      species influenced HMWP content. The results suggest that there is considerable
      variation among shiitake mushrooms in HMWP content and that production protocols
      influenced the HMWP content of mushrooms.

PMID- 12207469
TI  - Distribution of amylose, nitrogen, and minerals in rice kernels with various
      characters.
AB  - The distribution of chemical constituents is known not to be even within a rice
      kernel. To improve the eating quality of rice or to give it some special traits
      by adjusting the milling intensity, we investigated the distribution of amylose,
      nitrogen (N), and specific minerals (P, K, Mg, Ca, and Mn) in rice kernels of 11
      cultivars with various characteristics cultivated under similar conditions. The
      distributions of these constituents were determined using flour samples prepared
      consecutively by abrasive milling from the outer to the inner portions of hulled
      rice. In all the cultivars tested, N and the minerals were found to be more
      abundant in the outer than in the inner portion, but amylose was rich in the
      inner portion. P, Mg, K, and Mn were extremely rich in the outer portion, while N
      and Ca were only relatively rich there. Koshihikari, which is the most popular
      cultivar in Japan because of its excellent eating quality, showed the highest
      Mg/K ratio in the outermost portion of polished rice. The color of flour samples
      became pure white going from outside portions toward the center of the kernel,
      even if the sample was from red rice or purple-black rice because only the
      surface of hulled rice contains pigments. These findings suggest that the outer
      portion contains various compounds other than starch and the inner portion
      contains relatively pure starch. Rice palatability and other characteristics can
      be improved through controlling the degree of milling using the biased
      distribution of chemical constituents within a rice kernel.

PMID- 12207471
TI  - Flavonoids and antioxidant capacity of Georgia-grown Vidalia onions.
AB  - Vidalia onion varieties Nirvana, DPS 1032, Yellow 2025, King-Midas, and SBO 133
      grown at Vidalia, Georgia, were analyzed for flavonoid content. A high
      performance liquid chromatographic (HPLC) method with photodiode array detection
      was used for quantification. Compounds were analyzed as aglycons after acid
      hydrolysis with 1.2 M HCl. Identification of each compound was based on
      comparison of its retention time and UV spectra with those of pure commercial
      standards. Three major flavonoids, kaempferol, myricetin, and quercetin, were
      identified and quantified. Quercetin was the major flavonoid (7.70-46.32 mg/100 g
      fresh weight, FW) present in all varieties, followed by myricetin (2.77-4.13
      mg/100 g FW). Minor quantities of kaempferol (1.10-1.98 mg/100 g FW) were also
      detected. The total polyphenols and Trolox equivalent antioxidant capacity (TEAC)
      ranged from 73.33 to 180.84 mg/100 g FW and 0.92-1.56 microM TEAC/g FW,
      respectively. A positive but weaker correlation was obtained for total
      polyphenols versus antioxidant capacity. Nevertheless, a stronger correlation
      (r(2) = 0.34) was obtained between flavonoid content versus antioxidant capacity.
      The data indicate that Vidalia onions are a rich source of quercetin, and they
      also contain myricetin and kaempferol.

PMID- 12207472
TI  - Squalene content and antioxidant activity of Terminalia catappa leaves and seeds.
AB  - Squalene was identified by gas chromatography-mass spectrometry and high
      performance liquid chromatography (HPLC) spiking analyses in the supercritical
      CO(2) extracts of freeze-dried abscisic leaves of Terminalia catappa L. When the
      freeze-dried abscisic, senescent, mature, and immature leaves and seeds were
      subjected to supercritical CO(2) extraction at 40 degrees C and 3000 psi and HPLC
      quantitation, squalene contents were 12.29, 2.42, 1.75, 0.9, and 0% in the
      extracts and corresponding to 1499, 451, 210, 65, and 0 microg/g in the freeze
      dried sample, respectively. When the extracts were applied for antioxidative
      characterization by supplementation in an iron/ascorbate system with linoleic
      acid and in a pork fat storage system for inhibition of conjugated diene
      hydroperoxide (CDHP) formation or in a free radical scavenging system with 1,1
      diphenyl-2-picryl-hydrazyl (DPPH), the extracts of leaves exhibited potent
      antioxidative and DPPH scavenging activities and increased with an increase of
      leaf maturity. However, the seed extracts only exhibited potent inhibition of
      CDHP formation and very low DPPH scavenging activity.

PMID- 12207473
TI  - Changes in the HPLC phenolic profile of virgin olive oil from young trees (Olea
      europaea L. Cv. Arbequina) grown under different deficit irrigation strategies.
AB  - The HPLC phenolic profile of virgin olive oils obtained from young olive trees
      (Arbequina cv.) grown under different deficit irrigation strategies was studied.
      Deficit irrigation (RDI) did not affect all the phenolic compounds in the same
      way. Lignans, vanillic acid, vanillin, and the unknown phenolic compound named
      P24 increased in the oils from the most irrigated treatments. The secoiridoid
      derivatives and the unknown phenolic compound named P19 increased in the oils
      from the most stressed irrigation treatments. The period of growth where a water
      stress significantly affects the phenolic profile of oils was between pit
      hardening and the first stages of fruit growth and oil accumulation,
      independently of the water applied during the previous period to harvest. The
      phenolic profile and those parameters related to phenol content, oxidative
      stability, and the bitter index were significantly affected only in the most
      severe RDI strategies. Other strategies produced important savings in irrigation
      requirements and an increase in the water use efficiency without noticeably
      affecting the phenolic profile.

PMID- 12207474
TI  - Volatile chemicals identified in extracts from newly hybrid citrus, dekopon
      (Shiranuhi mandarin Suppl. J.).
AB  - Extracts from the peel and flesh of a citrus fruit, dekopon (Shiranuhi mandarin
      Suppl. J.), were obtained under reduced pressure followed by dichloromethane
      extraction. A total of 127 volatile chemicals were identified in the extracts
      using gas chromatography (GC) and gas chromatography-mass spectrometry (GC-MS).
      They included 11 monoterpenes, 32 monoterpenoids, 9 sesquiterpenes, 5
      sesquiterpenoids, 20 aliphatic alcohols, 14 aliphatic esters, 15 aliphatic
      aldehydes and ketones, 7 aliphatic acids, and 10 miscellaneous compounds. The
      major volatile constituents of the extract from the peel were d-limonene (2380.33
      mg/kg), myrcene (36.54 mg/kg), bisabolene (30.03 mg/kg), sabinene (21.12 mg/kg),
      trans-beta-ocimene (16.96 mg/kg), valencene (12.84 mg/kg), decanal (8.14 mg/kg),
      beta-phellandrene (4.53 mg/kg), citronellol (4.51 mg/kg), 4-terpineol (4.50
      mg/kg), linalool (4.13 mg/kg), and citronellyl acetate (3.63 mg/kg). The major
      volatile constituents of the extract from the flesh were ethyl acetate (21.54
      mg/kg), acetoin (7.23 mg/kg), 3-methylbutanol (2.79 mg/kg), p-mentha-cis-2,8-dien
      1-ol (1.01 mg/kg), 3-methylbutanoic acid (0.95 mg/kg), isobutanol (0.59 mg/kg),
      trans-isopiperitenol (0.58 mg/kg), p-mentha-trans-2,8-dien-1-ol, and trans
      carveol (0.44 mg/kg). Compositions of volatile chemicals in peel and flesh
      extract were considerably different: the peel extract was rich in terpenes,
      whereas the flesh extract was rich in aliphatic compounds.

PMID- 12207475
TI  - Mapping the distribution of DDT residues as DDE in the soils of the irrigated
      regions of northern New South Wales, Australia using ELISA and GIS.
AB  - An enzyme-linked immunosorbent assay (ELISA) specific for DDE [1,1-dichloro-2,2
      bis(4-chlorophenyl)ethylene] has been used to map DDT [1,1,1-trichloro-2,2-bis(4
      chlorophenyl)ethane)] residues in the top 10 cm of soil in three river valleys of
      northern New South Wales, Australia. Despite being almost 20 years since DDT was
      last applied for cotton growing in these areas, the relationship between sites of
      greatest application and current residue levels was strong. DDE concentrations in
      the range 0-2 ppm were found, although most the 389 soil samples examined
      contained less than 0.2 ppm of DDE. Although some relationship between mode of
      land use and current residue levels was apparent, this varied from valley to
      valley and may have reflected different farming practices and times of
      application. The study demonstrates that the combination of ELISA and
      geographical information system (GIS) analysis provides an effective means of
      displaying levels of soil contamination by a pesticide and the possible need for
      remediation.

PMID- 12207476
TI  - Sorption-desorption of "aged" sulfonylaminocarbonyltriazolinone herbicides in
      soil.
AB  - Sorption-desorption interactions of pesticides with soil determine the
      availability of pesticides in soil for transport, plant uptake, and microbial
      degradation. These interactions are affected by the physical and chemical
      properties of the pesticide and soil, and for some pesticides, their residence
      time in the soil. The objective of this study was to characterize sorption
      desorption of two sulfonylaminocarbonyltriazolinone herbicides incubated in soils
      at different soil moisture potentials. The chemicals were incubated in clay loam
      and loamy sand soils for up to 12 wks at -33 kPa and at water contents equivalent
      to 50 and 75% of that at -33 kPa. Chemicals were extracted sequentially with 0.01
      N CaCl(2) and aqueous acetonitrile, and sorption coefficients were calculated.
      Sufficient sulfonylaminocarbonyltriazolinone herbicides remained (>40% of that
      applied) during incubation to allow calculation of sorption coefficients. Aging
      significantly increased sorption as indicated by increased sorption coefficients.
      For instance, for sulfonylaminocarbonyltriazolinone remaining after a 12-wk
      incubation at -33 kPa, K(d) increased by a factor of 4.5 in the clay loam soils
      and by 6.6 in the loamy sand as compared to freshly treated soils. There was no
      effect of moisture potential on sorption K(d) values. These data show the
      importance of characterization of sorption-desorption in aged herbicide residues
      in soil, particularly in the case of prediction of herbicide transport in soil.
      In this case, potential transport of sulfonylaminocarbonyltriazolinone herbicides
      would be over-predicted if freshly treated soil K(d) values were used to predict
      transport.

PMID- 12207477
TI  - Behavior of metalaxyl and its pure R-enantiomer in sunflower plants (Helianthus
      annus).
AB  - A possible stereospecific and/or stereoselective mechanism of biodegradation for
      metalaxyl and metalaxyl-M was studied to elucidate their behavior in sunflower
      plants and to compare their biodegradation. Greenhouse experiments were carried
      out to confirm the same efficacy of the two fungicides against infections by
      Plasmopara helianthi in sunflower plants. The two fungicides appear to have the
      same behavior regarding both the protection against plant infections and the mode
      of translocation and the rate and pathway of biotransformation, but we have
      evidence that this biotransformation process is enantioselective. Furthermore, we
      propose procedures for a chromatographic separation of enantiomers and acid
      metabolites of the fungicides and for the determination of the R:S ratio by HPLC
      chiral analyses. This study emphasizes the importance of examining the fate of
      both stereoisomers of a chiral agrochemical in an environmental system for the
      correct use of enantiomerically pure agrochemical compounds.

PMID- 12207478
TI  - Quantitation of odor-active compounds in rye flour and rye sourdough using stable
      isotope dilution assays.
AB  - Application of the aroma extract dilution analysis on a flavor distillate
      prepared from freshly ground rye flour (type 1150) revealed 1-octen-3-one
      (mushroom-like), methional (cooked potato), and (E)-2-nonenal (fatty, green) with
      the highest flavor dilution (FD) factors among the 26 odor-active volatiles
      identified. Quantitative measurements performed by stable isotope dilution assays
      and a comparison to the odor thresholds of selected odorants in starch suggested
      methional, (E)-2-nonenal, and hexanal as contributors to the flour aroma, because
      their concentrations exceeded their odor thresholds by factors >100. Application
      of the same approach on a rye sourdough prepared from the same batch of flour
      revealed 3-methylbutanal, vanillin, 3-methylbutanoic acid, methional, (E,E)-2,4
      decadienal, 2,3-butanedione, and acetic acid as important odorants; their
      concentrations exceeded their odor thresholds in water and starch by factors
      >100. A comparison of the concentrations of 20 odorants in rye flour and the
      sourdough made therefrom indicated that flour, besides the fermentation process,
      is an important source of aroma compounds in dough. However, 3-methylbutanol,
      acetic acid, and 2,3-butanedione were much increased during fermentation, whereas
      (E,E)-2,4-decadienal and 2-methylbutanal were decreased. Similar results were
      obtained for five different flours and sourdoughs, respectively, although the
      amounts of some odorants in the flour and the sourdough differed significantly
      within batches.

PMID- 12207479
TI  - Aroma active components in aqueous kiwi fruit essence and kiwi fruit puree by GC
      MS and multidimensional GC/GC-O.
AB  - Gas chromatography-mass spectrometry (GC-MS) and multidimensional gas
      chromatography olfactometry (GC/GC-O) were utilized to study the aroma profile
      and the aroma active components of commercial kiwi essence and the initial fresh
      fruit puree. Totals of 29 and 33 components were identified and quantified in the
      essence and the puree, respectively. Ten components were quantified for the first
      time as constituents of the kiwi fruit including 3-penten-2-ol, 3-hydroxy-2
      butanone, 3-methyl-2-butenal, 2-hexanol, nonanal, 3-methyl-1-butanol, 2-methyl-1
      butanol, 3-methyl-2-butanone, 3-methyl 3-buten-2-one, and octane. Analysis of
      these samples by multidimensional gas chromatography-olfactometry (GC-O) allowed
      for the identification of >80% of the aroma active components present at level
      traces in this fruit. A total of 35 components appear to contribute to the aroma
      of kiwi fresh puree and its aqueous essence. Components described for the first
      time as constituents of the aroma profile in this fruit were 2-ethylfuran, 3
      methyl-1-butanol, 2-cyclohexen-1-one, (E,E)-2,6-nonadienal, diethyl succinate,
      and hexyl hexanoate.

PMID- 12207480
TI  - Structural determination and odor characterization of N-(2-mercaptoethyl)-1,3
      thiazolidine, a new intense popcorn-like-smelling odorant.
AB  - The chemical structure of a novel, roasty, popcorn-like-smelling aroma compound
      formed from the reaction of fructose with cysteamine was studied by high
      resolution mass spectrometry and nuclear magnetic resonance experiments. The
      structure of N-(2-mercaptoethyl)-1,3-thiazolidine exhibiting the extremely low
      odor threshold of 0.005 ng/L in air was finally confirmed by synthesis.

PMID- 12207481
TI  - Identification and quantitation of key aroma compounds formed in Maillard-type
      reactions of fructose with cysteamine or isothiaproline (1,3-thiazolidine-2
      carboxylic acid).
AB  - Fructose was reacted in the presence of either cysteamine (model A) or
      isothiaproline (model B) in aqueous buffer at 145 degrees C and pH 7.0.
      Application of an aroma extract dilution analysis on the bulk of the volatile
      compounds formed in model A revealed 5-acetyl-3,4-dihydro-2H-1,4-thiazine (19), N
      (2-mercaptoethyl)-1,3-thiazolidine (16), 4-hydroxy-2,5-dimethyl-3(2H)-furanone
      (15), and 2-acetyl-2-thiazoline (11) as the key aroma compounds among the 10
      odorants detected. A similar set of aroma compounds was formed when
      isothiaproline was reacted (model B), but the flavor dilution factors were
      generally lower. Substitution of the buffer by silica gel/water (9 + 1 w/w) in
      both models and application of 150 degrees C for 10 min also gave the same key
      odorants from both thio compounds; however, under these conditions isothiaproline
      was the better precursor of, in particular, 19 and 11. Quantitative measurements
      performed by means of stable isotope dilution assays revealed a significant
      effect of the pH on odorant formation. For example, in model A, formation of 19
      as well as of 11 was suppressed at pH values <5.0. A clear maximum was, however,
      found for 19 at pH 7.0 (approximately 1 mol % yield), whereas 11 increased with
      increasing pH from 7.0 to 9.0.

PMID- 12207482
TI  - Real-time monitoring of thermal flavor generation in skim milk powder using
      atmospheric pressure chemical ionization mass spectrometry.
AB  - The feasibility of monitoring volatile flavor compounds formed by thermal
      treatment of skimmed milk powder in real time by atmospheric pressure chemical
      ionization mass spectrometry (APCIMS) was established. Skim milk powder samples
      were heated isothermally (70 to 120 degrees C) at different moisture contents
      (2.2 and 12.7 g water/100 g dry solids). Headspace was sampled and analyzed
      continuously in full scan mode (30-180 amu) by APCIMS. The identity of the
      volatile compounds monitored by APCIMS was confirmed by coupled GC-EI-APCIMS. The
      concentration measured by the APCIMS was the net effect of three processes,
      namely formation of the compound, partition from the skim milk powder into the
      gas phase, and dilution due to the headspace sampling method used. Preliminary
      experiments established that the technique could follow the effects of heating
      temperature and moisture content on the formation of selected compounds from skim
      milk powder.

PMID- 12207483
TI  - Monitoring chemical and physical changes during thermal flavor generation.
AB  - On-line techniques were developed to monitor chemical and physical changes
      occurring during the heating of skim milk powder (SMP). Atmospheric pressure
      chemical ionization mass spectrometry (APCIMS) followed the generation and
      release of volatile compounds from SMP in a packed-bed reactor. Operating
      conditions were optimized to avoid condensation of high boiling compounds such as
      maltol, and the system was highly reproducible (CV < 7%). Differential scanning
      calorimetry (DSC) of SMP identified a potential glass transition at an onset
      temperature of 67.9 degrees C and a series of exothermic events that were related
      to different stages of the Maillard reaction. No lactose crystallization was
      found after heating. Using a heated stage reflectance FTIR device, spectra were
      obtained at different temperatures. Analysis of the data showed a correlation
      between the intensity ratio at wavenumbers 1017 and 1064 cm(-1) and the glass
      transition measured by DSC. This FTIR system was not sensitive enough to detect
      Maillard intermediates. Combining data from the three techniques provides a
      fuller picture of the physical changes during the Maillard reaction and their
      effects on the chemical reactions.

PMID- 12207484
TI  - Identification of distinctive volatile compounds in fish sauce.
AB  - To make clear the distinctive odorants of fish sauce, addition tests were carried
      out with respect to deodorized fish sauce samples. Volatiles from the headspace
      gas of nontreated fish sauce and deodorized fish sauce were characterized by gas
      chromatography-olfactometry and gas chromatography-mass spectrometry. Four
      compounds contributing to the distinctive odor of fish sauce were 2
      methylpropanal, 2-methylbutanal, 2-ethylpyridine, and dimethyl trisulfide.
      Addition tests (quantitative descriptive analysis) with respect to the four
      odorants showed that contributors to the fishy aroma were 2-ethylpyridine and
      dimethyl trisulfide and that all four odorants contributed to the sweaty aroma.
      Furthermore, the fecal note of fish sauce was essential with 2-ethylpyridine and
      dimethyl trisulfide, and the rancid note was essential with all four odorants.

PMID- 12207485
TI  - Production of cod (Gadus morhua) muscle hydrolysates. Influence of combinations
      of commercial enzyme preparations on hydrolysate peptide size range.
AB  - The complement of enzyme activities of a selection of commercial protease
      preparations were determined using fluorogenic substrates. Alcalase was used in
      combination with other commercial enzyme preparations to produce cod muscle
      (Gadus morhua) hydrolysates. Each muscle hydrolysate was characterized with
      respect to the percentage degree of hydrolysis (DH %), peptide molecular weight
      range, and free amino acid content. The enzyme preparations containing
      predominantly protease or endopeptidase activities achieved high DH % and
      produced significant amounts of peptides below a molecular weight of 3000.
      Alcalase combined with exopeptidase-rich preparations produced hydrolysates rich
      in low-molecular-weight peptides. Selecting combinations of enzyme preparations
      with complementary activity profiles could be used to manipulate the peptide
      molecular weight profile of hydrolysates.

PMID- 12207486
TI  - Isolation and characterization of immunoglobulin in yolk (IgY) specific against
      hen egg white lysozyme by immunoaffinity chromatography.
AB  - Six hens were intramuscularly (im) immunized once a week for 3 weeks using
      chicken egg white lysozyme (LS) as antigen. Antibody (immunoglobulin in yolk,
      IgY) ELISA values of 10(3)-fold diluted yolk were almost as high as 1.879 in the
      sixth week and maintained a value of 0.756 in the eighth week after the initial
      immunization treatment. The purification efficiency (specific activity of
      purified IgY against LS/specific activity of antibody in yolk against LS) of IgY
      specific against LS isolated by laboratory-prepared LS-bound (IgY-) Sepharose 4
      Fast Flow immunoaffinity column was approximately 3380. By applying various
      amounts (0-22 mg) of the thusly obtained IgY specific against LS to the
      immunoaffinity column, the binding capacity (q(m)) and dissociation constant
      (K(d), M(-1)) of such immunoaffinity gel for IgY against LS were found to be 0.68
      mg of IgY/mL of wet gel (0.54 mg of IgY/mg of LS) and 7.13 x 10(-6) M,
      respectively, as determined by Langmuir-type adsorption isotherms.

PMID- 12207487
TI  - Physicochemical and nitrogen solubility properties of Bacillus proteinase
      hydrolysates of sodium caseinate incubated with transglutaminase pre- and post
      hydrolysis.
AB  - Sodium caseinate (NaCN), hydrolyzed with Protamex, a Bacillus proteinase
      preparation, to 0.5, 1.3, and 17.5% degrees of hydrolysis, was incubated with
      transglutaminase (TGase) for 3, 42, and 290 min at enzyme/substrate ratios of 1,
      1, and 10% (w/w), respectively, pre- and post-hydrolysis. The electrophoretic,
      reversed-phase high-performance liquid chromatography (RP-HPLC) and nitrogen
      solubility profiles of the modified products were investigated. Combinations of
      hydrolysis and incubation with TGase generated products displaying novel
      physicochemical and nitrogen solubility properties. Significant changes in sodium
      dodecyl sulfate (SDS) and urea polyacrylamide gel electrophoresis profiles were
      apparent in the modified caseinate samples. Extensive TGase cross-linking
      resulted in polymers that were unable to enter the resolving gel during SDS
      polyacrylamide gradient gel electrophoresis. Extensive combined enzymatic
      modification resulted in peptides eluting earlier on RP-HPLC than limited
      combined enzymatic modification or limited hydrolysis. Combination of enzymatic
      treatments resulted in significantly (P < 0.005) improved solubility around pH
      4.6, compared to incubation with TGase or hydrolysis of NaCN alone.

PMID- 12207488
TI  - Partial purification, characterization, and thermal and high-pressure
      inactivation of pectin methylesterase from carrots (Daucus carrota L.).
AB  - Pectin methylesterase (PME) from carrots (Daucus carrota L.) was extracted and
      purified by affinity chromatography on a CNBr-Sepharose 4B-PME inhibitor column.
      A single protein and PME activity peak was obtained. A biochemical
      characterization in terms of molar mass (MM), isoelectric points (pI), and
      kinetic parameters of carrot PME was performed. In a second step, the thermal and
      high-pressure stability of the enzyme was studied. Isothermal and combined
      isothermal-isobaric inactivation of purified carrot PME could be described by a
      fractional-conversion model.

PMID- 12207489
TI  - Ability of lipid hydroperoxides to partition into surfactant micelles and alter
      lipid oxidation rates in emulsions.
AB  - Lipid hydroperoxides are important factors in lipid oxidation due to their
      ability to decompose into free radicals. In oil-in-water emulsions, the physical
      location of lipid hydroperoxides could impact their ability to interact with
      prooxidants such as iron. Interfacial tension measurements show that linoleic
      acid, methyl linoleate, and trilinolein hydroperoxides are more surface-active
      than their non-peroxidized counterparts. In oil-in-water emulsion containing
      surfactant (Brij 76) micelles in the continuous phase, linoleic acid, methyl
      linoleate, and trilinolein hydroperoxides were solubilized out of the lipid
      droplets into the aqueous phase. Brij 76 solubilization of the different
      hydroperoxides was in the order of linoleic acid > trilinolein > or = methyl
      linoleate. Brij 76 micelles inhibited lipid oxidation of corn oil-in-water
      emulsions with greater inhibition of oxidation occurring in emulsions containing
      linoleic acid hydroperoxides. Surfactant solubilization of lipid hydroperoxides
      could be responsible for the ability of surfactant micelles to inhibit lipid
      oxidation in oil-in-water emulsions.

PMID- 12207490
TI  - Antioxidants, free radicals, storage proteins, and proteolytic activities in
      wheat (Triticum durum) seeds during accelerated aging.
AB  - Accelerated aging was performed by incubation of wheat seeds at 40 degrees C and
      100% relative humidity for 3, 4, 6, 10, and 14 days. The effects of the treatment
      on seed germinability and on several biochemical characteristics of flour
      (carotenoids, free radical and protein contents, and proteolytic activity) and
      gluten (free radical content and flexibility) were evaluated. A decrease of
      germinability was found during aging, the germination being completely inhibited
      after 14 days. The lutein content decreased gradually, without going to zero,
      while that of free radicals increased. A reduction of soluble proteins and a
      degradation of glutenins and gliadins were observed, associated with a
      substantial increase of protease activity and a decrease in gluten flexibility.
      The results were discussed in reference to those previously obtained by natural
      aging of wheat seeds of the same species and cultivar.

PMID- 12207491
TI  - Modulation of antioxidant compounds in organic vs conventional fruit (peach,
      Prunus persica L., and pear, Pyrus communis L.).
AB  - Despite the increasing interest in organic products, knowledge about how
      different levels of fertilization affect nutritionally relevant components is
      still limited. The concentration of polyphenols and the activity of
      polyphenoloxidase (PPO), together with the content in ascorbic acid, citric acid,
      and alpha- and gamma-tocopherol, were assayed in conventional and organic peach
      (Prunus persica L., cv. Regina bianca) and pear (Pyrus communis L., cv.
      Williams). 2-Thiobarbituric acid reactive substances and the
      tocopherolquinone/alpha-tocopherol ratio were used as markers of oxidative damage
      in fruits. A parallel increase in polyphenol content and PPO activity of organic
      peach and pear as compared with the corresponding conventional samples was found.
      Ascorbic and citric acids were higher in organic than conventional peaches,
      whereas alpha-tocopherol was increased in organic pear. The concentration of
      oxidation products in organic samples of both fruits was comparable to that of
      the corresponding conventional ones. These data provide evidence that an
      improvement in the antioxidant defense system of the plant occurred as a
      consequence of the organic cultivation practice. This is likely to exert
      protection against damage of fruit when grown in the absence of pesticides.

PMID- 12207492
TI  - Methyl linoleate oxidation in the presence of bovine serum albumin.
AB  - The oxidation of methyl linoleate (LMe) in the presence of bovine serum albumin
      (BSA) was studied to analyze both the processes involved when lipid oxidation
      occurs in the presence of proteins and the relative progression of the several
      reactions implicated. The disappearance of LMe, the formation of primary and
      secondary lipid oxidation products, the loss of essential amino acids, and the
      production of oxidized lipid/amino acid reaction products (OLAARPs) were studied
      as a function of incubation time. During the first steps of lipid oxidation, LMe
      was converted quantitatively to methyl linoleate hydroperoxides, which were very
      rapidly degraded to either secondary products of lipid oxidation or OLAARPs. No
      significant differences were identified in the major lipid oxidation products
      formed in incubations with or without proteins, indicating that mechanisms for
      formation of these compounds are similar in both cases. In addition, no
      significant differences were observed between the time-courses of formation of
      secondary oxidation products and OLAARPs, suggesting that hydroperoxide
      decomposition and OLAARP formation occur simultaneously when the lipid oxidation
      process takes place in the presence of proteins. Furthermore, OLAARP formation
      seems to be an unavoidable process that should be considered as a last step in
      the lipid peroxidation process.

PMID- 12207493
TI  - Oxidative dimers produced from protocatechuic and gallic esters in the DPPH
      radical scavenging reaction.
AB  - DPPH (2,2-diphenyl-1-picrylhydrazyl) radical scavenging reactions of
      protocatechuic and gallic acids, and their methyl esters, have been investigated
      by NMR. In acetone, methyl protocatechuate was gradually converted to a Diels
      Alder adduct of two molecules of the intermediate quinone in the reaction with
      DPPH radical, whereas methyl gallate rapidly gave a symmetrical dimer via a
      putative quinone precursor. Both dimers are rather unstable and their structures
      have been deduced by in situ NMR measurements of the reaction mixtures. Gallic
      acid also gave a corresponding symmetrical dimer in the same reaction as methyl
      gallate, although protocatechuquinone produced from protocatechuic acid did not
      yield a Diels-Alder adduct, unlike its methyl ester. Interestingly, these dimer
      formations were not observed in methanol solution.

PMID- 12207494
TI  - Degradation of the Amadori compound N-(1-deoxy-D-fructos-1-yl)glycine in aqueous
      model systems.
AB  - The fate of the Amadori compound N-(1-deoxy-D-fructos-1-yl)glycine (DFG) was
      studied in aqueous model systems as a function of time and pH. The samples were
      reacted at 90 degrees C for up to 7 h while maintaining the pH constant at 5, 6,
      7, or 8. Special attention was paid to the effect of phosphate on the formation
      of glycine and the parent sugars glucose and mannose, as well as formic and
      acetic acid. These compounds and DFG were quantified by high-performance anion
      exchange chromatography. The rate of DFG degradation increased with pH. Addition
      of phosphate accelerated this reaction, particularly at pH 5-7. The rate of
      glycine formation increased with pH in both the absence and presence of
      phosphate. High glycine concentrations (60-70 mol %) were obtained, preferably at
      pH 6-8 with phosphate. However, the yield of glycine formed from DFG decreased at
      the advanced reaction stage for all pH values studied, both in water and in
      phosphate buffer. The rate of parent sugar formation increased from pH 5 to pH 7
      in the absence of phosphate, leading to glucose and mannose in a constant ratio
      of 7:3. Addition of phosphate accelerated this reaction, yielding up to 18%
      parent sugars, most likely formed by reverse Amadori rearrangement. The formation
      rate of acetic and formic acid increased with increasing pH. The sum of both
      acids attained 76 mol %. However, the acetic acid concentrations were much higher
      than those of formic acid.

PMID- 12207495
TI  - Antioxidative activity of heterocyclic compounds found in coffee volatiles
      produced by Maillard reaction.
AB  - Typical heterocyclic compounds substituted with various functional groups found
      in Maillard reaction products were examined for antioxidant activity. Pyrroles
      exhibited the greatest antioxidant activity among all heterocyclic compounds
      tested. All pyrroles inhibited hexanal oxidation by almost 100% at a
      concentration of 50 microg/mL over 40 days. Addition of formyl and acetyl groups
      to a pyrrole ring enhanced antioxidative activity remarkably. Pyrrole-2
      carboxaldehyde, 2-acetylpyrrole, 1-methyl-2-pyrrolecarboxaldehyde, and 2-acetyl-1
      methylpyrrole inhibited hexanal oxidation by >80% at 10 microg/mL. Unsubstituted
      furan exhibited the greatest antioxidant activity among furans tested. Addition
      of all functional groups used in this study to furan decreased antioxidative
      activity. The antioxidant activity of thiophene increased with the addition of
      methyl and ethyl groups, but the addition of formyl or acetyl groups to thiophene
      decreased antioxidant activity. Thiazoles and pyrazines were ineffective
      antioxidants at all concentrations tested. Reaction of all heterocyclic compounds
      with hydrogen peroxide resulted in the formation of various oxidized products.

PMID- 12207496
TI  - Erythritol attenuates the diabetic oxidative stress through modulating glucose
      metabolism and lipid peroxidation in streptozotocin-induced diabetic rats.
AB  - We investigated the effects of erythritol on rats with streptozotocin- (STZ-)
      induced diabetes mellitus. Oral administration of erythritol [100, 200, or 400 mg
      (kg body weight)(-1) day(-1) for 10 days] to rats with STZ-induced diabetes
      resulted in significant decreases in the glucose levels of serum, liver, and
      kidney. Erythritol also reduced the elevated serum 5-hydroxymethylfurfural level
      that is glycosylated with protein as an indicator of oxidative stress. In
      addition, thiobarbituric acid-reactive substance levels of serum and liver and
      kidney mitochondria were dose-dependently lower in the erythritol-treated groups
      than in the control diabetic group. Furthermore, the serum creatinine level was
      reduced by oral administration of erythritol in a dose-dependent manner. These
      results suggest that erythritol affects glucose metabolism and reduces lipid
      peroxidation, thereby improving the damage caused by oxidative stress involved in
      the pathogenesis of diabetes.

PMID- 12207497
TI  - Antioxidant effects of isorhamnetin 3,7-di-O-beta-D-glucopyranoside isolated from
      mustard leaf (Brassica juncea) in rats with streptozotocin-induced diabetes.
AB  - To investigate the effects of isorhamnetin 3,7-di-O-beta-D-glucopyranoside
      (isorhamnetin diglucoside), a major flavonoid compound of mustard leaf, on
      oxidative stress due to diabetes mellitus, in vivo and in vitro studies were
      carried out. Oral administration of isorhamnetin diglucoside (10 or 20 mg/kg of
      body weight/day for 10 days) to rats with streptozotocin-induced diabetes
      significantly reduced serum levels of glucose and 5-(hydroxymethyl)furfural (5
      HMF), which is glycosylated with hemoglobin and is an indicator of oxidative
      stress. After intraperitoneal administration, isorhamnetin diglucoside did not
      show these activities. In addition, after oral administration, the thiobarbituric
      acid-reactive substance levels of serum, and liver and kidney mitochondria
      declined significantly compared with the control group in a dose-dependent
      manner, whereas after intraperitoneal administration these levels fell only
      slightly. On the basis of the oral and intraperitoneal results, it was
      hypothesized that isorhamnetin diglucoside was converted to its metabolite in
      vivo, and its conversion to its aglycone, isorhamnetin, by beta-glucosidase was
      confirmed; isorhamnetin acted as an antioxidant. Moreover, it was observed that
      isorhamnetin diglucoside had no effect on the 1,1-diphenyl-2-picrylhydrazyl
      radical, whereas isorhamnetin showed a potent antioxidant effect in vitro. In
      addition, intraperitoneal administration of isorhamnetin reduced serum glucose
      and 5-HMF levels. Furthermore, lipid peroxidation in blood, liver, and kidney
      associated with diabetes mellitus declined after the administration of
      isorhamnetin. These results suggest that isorhamnetin diglucoside is metabolized
      in vivo by intestinal bacteria to isorhamnetin and that isorhamnetin plays an
      important role as an antioxidant.

PMID- 12207498
TI  - Metabolism of polychlorinated dibenzo-p-dioxins (PCDDs) by human cytochrome P450
      dependent monooxygenase systems.
AB  - Metabolism of polychlorinated dibenzo-p-dioxins (PCDDs) by monooxygenase systems
      dependent on 12 forms of human cytochrome P450 (CYP) was examined with the
      recombinant yeast microsomes containing each of the human CYP. The metabolites of
      PCDDs were analyzed by HPLC and GC-MS. Remarkable metabolism by the multiple CYP
      forms was observed toward dibenzo-p-dioxin (DD) and mono-, di-, and trichloroDDs.
      The metabolism contained multiple reactions such as hydroxylation at an
      unsubstituted position, hydroxylation with migration of a chloride substituent,
      and hydroxylation with elimination of a chloride substituent. Although major CYPs
      in human liver such as CYP2C8, CYP2C9, and CYP3A4 showed no significant
      metabolism toward the PCDDs, CYP1A1 and CYP1A2 showed high catalytic activity
      toward DD and mono-, di-, and trichloroDDs. The kinetic parameters K(m)(app) and
      V(max) of the CYP1A1-dependent 8-hydroxylation activity of 2,3,7-trichloro-DD
      (2,3,7-triCDD) were estimated to be 0.30 microM and 51 (mol/min/mol of P450),
      respectively, suggesting that 2,3,7-triCDD was a good substrate for CYP1A1.
      However, none of the CYPs showed any detectable activity [<0.01 mol/min/mol of
      P450)] toward 2,3,7,8-tetraCDD. Substrate-induced absorption spectrum and
      inhibition studies indicated that CYP1A1 could bind 2,3,7,8-tetraCDD with
      considerably high affinity. It was strongly suggested that the long half-life
      (7.1 years) of 2,3,7,8-tetraCDD in humans was due to an extremely low activity of
      CYPs toward 2,3,7,8-tetraCDD in addition to its chemical stability.

PMID- 12207499
TI  - Nanostructured carbon arrays from block copolymers of polyacrylonitrile.
AB  - Arrays of graphitic carbon nanoclusters were obtained by pyrolysis of nanoscale
      phase-separated block copolymers of polyacrylonitrile and poly(n-butyl acrylate).
      Upon heating in an inert atmosphere to temperatures ranging from approximately
      400 to 1200 degrees C, polyacrylonitrile domains were converted into carbon
      nanoclusters, maintaining the overall shape and spacing, whereas the poly(n-butyl
      acrylate) phase was sacrificed. Preservation of the original nanoscale morphology
      of a block copolymer was possible only if pyrolysis was preceded by oxidation at
      temperatures of approximately 230 degrees C, in analogy with thermal
      stabilization of polyacrylonitrile precursor in the process used in the
      manufacturing of carbon fibers. Preorganization of the carbon precursor through
      self-assembly in block copolymers of polyacrylonitrile appears to be an
      attractive and robust strategy for templated synthesis of well-defined
      nanostructured carbon materials.

PMID- 12207500
TI  - Direct electrochemistry of cytochrome C at nanocrystalline boron-doped diamond.
AB  - Direct electron transfer of horse heart cytochrome c is measured at a
      nanocrystalline boron-doped diamond thin-film electrode. A quasi-reversible,
      diffusion-controlled cyclic voltammetric response is observed for untreated
      diamond. The peak currents change linearly with the concentration, and
      importantly, there is no electrode fouling. The results, observed for a hydrogen
      terminated and uncharged surface, (i.e., no ionizable carbon-oxygen functional
      groups), raise interesting questions about the necessary surface interactions of
      cytochrome c for relatively rapid electrode kinetics.

PMID- 12207501
TI  - Supercritical fluid-mediated alumination of mesoporous silica and its beneficial
      effect on hydrothermal stability.
AB  - We have investigated the use of supercritical fluids (SCFs) as carriers/solvents
      during the postsynthesis alumination of mesoporous silica. SCFs were found to be
      ideally suited for transport of Al into mesoporous silica and to lead to Al
      grafted aluminosilicate materials that exhibit exceptional hydrothermal (steam)
      stability even for highly aluminated materials. The improvements in steam
      stability arising from the use of SCFs as grafting media (as compared to aqueous
      or organic solvents) are remarkable, especially for Al-grafted MCM-41 materials
      with high (Si/Al < or = 10) Al contents. It is proposed that under supercritical
      fluid conditions Al is sorbed on the surface of the pore walls of the host Si-MCM
      41 with little penetration into the pore wall region, that is, the low solvating
      power of SCFs ensures the deposition of Al onto rather than into the silica
      framework. This is because the host silica framework cannot undergo any
      significant hydrolysis (to allow penetration of Al into the pore wall region)
      during the SCF-mediated alumination. Removal of the Al (i.e., dealumination)
      which occurs during steaming is therefore less detrimental to the structural
      integrity of SCF-grafted Al-MCM-41 materials since any dealumination that occurs
      will not involve removal of Al from deep within the pore walls.

PMID- 12207502
TI  - Nanotube formation favored by chalcogen-chalcogen interactions.
AB  - Close contacts between sulfur, selenium, and tellurium centers are used to
      construct nanotubes in the solid state which are able to host other molecules.

PMID- 12207503
TI  - A single-molecule probe based on intramolecular electron transfer.
AB  - Detecting structure, dynamics, and chemical reactions at the single-molecule
      level represents the ultimate degree of sensitivity for sensing and imaging.
      There is a tremendous need to develop new molecular systems and methodology for
      single-molecule-based sensing. This work presents for the first time the single
      molecule spectroscopy of a new molecular probe which uses an intramolecular
      electron transfer mechanism to detect binding, local structure, and interfacial
      processes. Moreover, we show how information about the interaction of these
      probes with their environment is obtained from an analysis of the intensity,
      duration and time-varying behavior of the single-molecule fluorescence.

PMID- 12207504
TI  - Kanosamine biosynthesis: a likely source of the aminoshikimate pathway's nitrogen
      atom.
AB  - The biosynthetic source of the nitrogen atom incorporated into the aminoshikimate
      pathway has remained a question for some time. 3-Amino-3-deoxy-D-fructose 6
      phosphate has previously been demonstrated to be a precursor to 4-amino-3,4
      dideoxy-D-arabino-heptulosonic acid 7-phosphate and 3-amino-5-hydroxybenzoic acid
      via the inferred intermediacy of 1-deoxy-1-imino-D-erythrose 4-phosphate in
      Amycolatopsis mediterranei cell-free extract. This investigation examines the
      possibility that the natural product kanosamine might be a precursor to 3-amino-3
      deoxy-D-fructose 6-phosphate. Kanosamine 6-phosphate was synthesized by a
      chemoenzymatic route and incubated in A. mediterranei cell-free lysate along with
      D-ribose 5-phosphate and phosphoenolpyruvate. Formation of 4-amino-3,4-dideoxy-D
      arabino-heptulosonic acid 7-phosphate and 3-amino-5-hydroxybenzoic acid was
      observed. Subsequent incubation in A. mediterranei cell-free lysate of glutamine
      and NAD with UDP-glucose resulted in the formation of kanosamine. The
      bioconversion of UDP-glucose into kanosamine along with the bioconversion of
      kanosamine 6-phosphate into 4-amino-3,4-dideoxy-D-arabino-heptulosonic acid 7
      phosphate and 3-amino-5-hydroxybenzoic acid suggests that kanosamine biosynthesis
      is the source of the aminoshikimate pathway's nitrogen atom.

PMID- 12207505
TI  - Characterization of the early stage aminoshikimate pathway in the formation of 3
      amino-5-hydroxybenzoic acid: the RifN protein specifically converts kanosamine
      into kanosamine 6-phosphate.
AB  - The biosynthesis of 3-amino-5-hydroxybenzoic acid (AHBA), precursor of the
      ansamycin and mitomycin antibiotics, proceeds by the aminoshikimate pathway from
      3,4-dideoxy-4-amino-D-arabino-heptulosonic acid 7-phosphate (aminoDAHP).
      Identification of RifN, product of one of three genes from the rifamycin
      biosynthetic gene cluster known to be essential for aminoDAHP formation, as a
      specific kanosamine (3-deoxy-3-amino-D-glucose) 6-kinase establishes kanosamine
      and its 6-phosphate as specific intermediates in AHBA formation. This suggests a
      hypothetical reaction sequence for aminoDAHP formation, and thus for the early
      steps of AHBA biosynthesis, starting from UDP-D-glucose and introducing the
      nitrogen by oxidation and transamination at C-3.

PMID- 12207506
TI  - Hydrogen bonds seal single-molecule capsules.
AB  - In the presence of methanol the tetrakis(benzoxazines) complex
      tetramethylammonium cation within the cavity, and the cavity is completely sealed
      by two intramolecular hydrogen bonds between amide groups. The Cl(-) anion is
      found external to the cavity. In CHCl(3), Me(4)N(+) is complexed within the
      cavity, but the Cl(-) anion acts as a stopper in the upper rim of the cavity,
      hydrogen-bonded to the amide groups. The solution results are supported by single
      crystal X-ray structural studies of both the single-molecule molecular capsules,
      and those stoppered by Cl(-).

PMID- 12207507
TI  - Substrate-facilitated assembly of elastin-like peptides: studies by variable
      temperature in situ atomic force microscopy.
AB  - Extended duration in situ variable-temperature atomic force microscopy performed
      on a series of coacervating hydrophobic peptides based on human elastin revealed
      a novel multistage surface assembly process. Formation of epitaxially arranged
      peptide rods was preceded by rapid expansion of a two-dimensional film on the
      nucleating substrate, a process facilitated by specific hydrophobic peptide
      substrate and intrapeptide interactions.

PMID- 12207508
TI  - A novel, cell-permeable, fluorescent probe for ratiometric imaging of zinc ion.
AB  - Zn(2+) plays important roles in various biological systems; as a result, the
      development of tools that can visualize chelatable Zn(2+) has attracted much
      attention recently. We report here newly synthesized fluorescent sensors for
      Zn(2+), ZnAF-Rs, whose excitation maximum is shifted by Zn(2+) under
      physiological conditions. Thus, these sensors enable ratiometric imaging, which
      is a technique to reduce artifacts by minimizing the influence of extraneous
      factors on the fluorescence of a probe. Ratiometric measurement can provide
      precise data, and some probes allow quantitative detection. ZnAF-Rs are the first
      ratiometric fluorescent sensors for Zn(2+) that enable quantitative analysis
      under physiological conditions. ZnAF-Rs also possess suitable K(d) for
      applications, and high selectivity against other biologically relevant cations,
      especially Ca(2+). Using these probes, changes of intracellular Zn(2+)
      concentration in cultured cells were monitored successfully. We believe that
      these probes will be extremely useful in studies on the biological functions of
      Zn(2+).

PMID- 12207509
TI  - Reintroducing anisotropic interactions in magic-angle-spinning NMR of half
      integer quadrupolar nuclei: 3D MQMAS.
AB  - Selective reintroduction of anisotropic interactions such as the chemical shift
      anisotropy (CSA) and homonucler dipolar (HMD) coupling were implemented in a high
      resolution NMR spectroscopy for half-integer quadrupolar nuclei. Rotary resonance
      recoupling (R(3)) combined with the multiple-quantum magic-angle spinning (MQMAS)
      in a three-dimensional (3D) experiment provides not only site-specific high
      resolution spectra to yield the quadrupolar interaction parameters but also the
      CSA or HMD interaction parameters. This 3D experiment provides an avenue for the
      complete local structural information of half-integer quadrupolar nuclei. Three
      dimensional MQMAS experiments incorporating R(3) of HMD and CSA interactions were
      demonstrated on model compounds containing (11)B, (23)Na, and (87)Rb nuclei.

PMID- 12207510
TI  - Effect of bond-length alternation in molecular wires.
AB  - Current-voltage (I-V) characteristics for metal-molecule-metal junctions formed
      from three classes of molecules measured with a simple crossed-wire molecular
      electronics test-bed are reported. Junction conductance as a function of
      molecular structure is consistent with I-V characteristics calculated from
      extended Huckel theory coupled with a Green's function approach, and can be
      understood on the basis of bond-length alternation.

PMID- 12207511
TI  - The topochemical 1,6-polymerization of a triene.
AB  - The first topochemical 1,6-polymerization of a triene has been observed. The
      required supramolecular structure for this polymerization was achieved by the pi
      pi stacking of the isonicotinate functionality. The crystal environment of this
      polymerization reaction controlled both the molecular and supramolecular
      structure of the polymer and allowed its structure to be determined by single
      crystal X-ray diffraction.

PMID- 12207512
TI  - Dramatic switching of protein kinase C agonist/antagonist activity by modifying
      the 12-ester side chain of phorbol esters.
AB  - A dramatic switching of PKC agonist and antagonist activity was observed by
      modification of the hydrophilicity of the 12-ester side chain of phorbol. Thus,
      phorbol ester 4 that contains a glycol at the 12-ester chain demonstrated a pure
      and significant antagonist ability of PKC; however, 3 that contains an alkanol at
      the 12-ester chain demonstrated a potent PKC agonist activity. On the basis of
      the structural difference between 3 and 4 and results of the partition assay in
      the Hela cell/PBS buffer system, we propose that 4 acts as a translocation poison
      of the PKC-phorbol ester complex. The approach of controlling the
      agonist/antagonist activity of phorbol esters by the nature (i.e.,
      hydrophilicity, charge, and rigidity, etc.) of the 12-ester chain may be very
      useful for developing selective PKC inhibitors and a potential pharmaceutical
      compound for anticancer therapies.

PMID- 12207514
TI  - Multiple emissions and brilliant white luminescence from gold(I) O,O'
      di(alkyl)dithiophosphate dimers.
AB  - The Au(I) dimers Au(2)[S(2)P(OR)(2)](2) for R = Me, Et are found to exhibit a
      structure in which aurophilic interactions yield one-dimensional Au...Au chains
      with intermolecular contacts (3.09-3.16 A) similar to the Au...Au distances
      within the dimers (3.10-3.18 A). The dimers are luminescent in the solid state
      and become brilliantly emissive at low temperatures. At 77 K,
      Au(2)[S(2)P(OMe)(2)](2) shows multiple emission bands. The two higher energy
      bands at 415 and 456 nm are assigned to (1)MC and (3)MC on the basis of lifetime
      measurements (20 ns and 2.16 micros, respectively) and concentration-related
      effects, while the lower energy band at 560 nm is attributed to a LMCT excited
      state. In frozen glasses of different solvents, Au(2)[S(2)P(OMe)(2)](2) as well
      as the Et and n-Pr derivatives exhibit a bright luminescence of different colors
      and striking thermochromism of the emission.

PMID- 12207513
TI  - Snapshots of dioxygen activation by copper: the structure of a 1:1 Cu/O(2) adduct
      and its use in syntheses of asymmetric Bis(mu-oxo) complexes.
AB  - The X-ray structure of a 1:1 Cu/O(2) adduct revealed side-on (eta(2)) O(2)
      coordination. Density functional calculations corroborated the structure,
      indicated a significant contribution of a Cu(III)-(O(2)(2-)) resonance form, and
      provided insights into the key bonding interactions. Reaction of a 1:1 adduct
      supported by a slightly different beta-diketiminate ligand with Cu(I) reagents
      resulted in the formation of novel asymmetric bis(mu-oxo) complexes that were
      identified by EPR, UV-vis, and Raman spectroscopy, as well as by an X-ray
      structure in one instance.

PMID- 12207515
TI  - EXAFS investigations of the mechanism of facilitated ion transfer into a room
      temperature ionic liquid.
AB  - The Sr(II)-crown ether complexes formed in a room-temperature ionic liquid
      (RTIL), 1-methyl-3-pentylimidazolium bis[(trifluoromethyl)sulfonyl]amide, have
      been studied by X-ray absorption fine structure measurements at the Sr K-edge.
      When a Sr(NO(3))(2)-crown ether complex is directly dissolved in a water
      saturated RTIL, both nitrate ligands and the crown ether coordinate the Sr, as
      observed in a conventional two-phase water-octanol system. When the cationic Sr
      crown ether complex is created in a two-phase water-RTIL system, however, only
      cationic Sr-crown ether complexes are observed in the RTIL phase. This difference
      in the coordination complexes arises from differences in the mechanism of cation
      extraction between the RTIL and conventional molecular organic solvents, a
      finding with important implications for synthesis, catalysis, and ion separations
      using two-phase water-RTIL systems.

PMID- 12207516
TI  - Three-bond sugar-base couplings in purine versus pyrimidine nucleosides: a DFT
      study of Karplus relationships for (3)J(C2/4-H1') and (3)J(C6/8-H1') in DNA.
AB  - (3)J(C2/4-H1') and (3)J(C6/8-H1') scalar spin-spin coupling constants have been
      calculated for deoxyadenosine, deoxyguanosine, deoxycytidine, and deoxythymidine
      as functions of the glycosidic torsion angle chi by means of density functional
      theory. Except for deoxythymidine, (3)J(C2/4-H1') depends little on the base
      type. On the contrary, (3)J(C6/8-H1') follows the usual trans to cis ratio
      ((3)J(C-H(cis)) < (3)J(C-H(trans))) for purine nucleosides, but reveals the
      opposite relation ((3)J(C-H(cis)) > (3)J(C-H(trans))) for pyrimidine nucleosides.
      Our results compare well with the experiment for deoxyguanosine and predict a
      novel trend in the case of pyrimidine bases for which no NMR results are
      available in the syn region. A breakdown of the key Fermi contact part of
      (3)J(C6/8-H1') into MO contributions rationalizes this trend in terms of an
      unusual coupling mechanism in the syn orientation that is very effective for
      pyrimidine nucleosides and considerably weaker for purine nucleosides.

PMID- 12207517
TI  - Single-crystal Al(18)B(4)O(33) microtubes.
AB  - Aluminum borate microtubes were prepared in excellent yield by annealing the
      Al(2)O(3)-NaBH(4)-NiCl(2) starting materials at 1050 degrees C under N(2)(H(2))
      atmosphere. The tubes are usually open at each end with the outer diameters
      narrowly distributed at ca. 1 microm. XRD results and TEM analysis identified the
      composition of these tubes as single-crystal orthorhombic Al(18)B(4)O(33). These
      newly discovered ceramic microtubes with open ends have a variety of promising
      applications such as being filled with other materials for protection or for the
      fabrication of novel composites or filtering media.

PMID- 12207518
TI  - Electrochemical metalloporphyrin-catalyzed reduction of chlorite.
AB  - We measured the redox stoichiometry and rate constants for the electrochemical
      reduction of ClO(2)(-) at pH 7, catalyzed by a series of metalloporphyrins of Mn,
      Fe, and Co with different proximal and distal environments. A clean four-electron
      reduction was observed. The catalytic activity correlates well with that observed
      in reduction of H(2)O(2). The axial imidazole and/or a redox-active distal metal
      (Cu or Co) increases the turnover frequency in several compounds. The
      metalloporphyrins were inert to ClO(x)(-) (x = 3,4) and IO(3)(-) but catalyzed
      facile two-electron reduction of IO(4)(-); six-electron reduction of BrO(3)(-)
      was also observed.

PMID- 12207519
TI  - Strained silacycles in organic synthesis: the tandem aldol-allylation reaction.
AB  - Allyl(crotyl)enolsilanes, when constrained in a five-membered ring with a 1,2
      diol, react with aldehydes in a tandem aldol-allylation reaction to give
      polyketide fragments. These experimentally trivial and efficient reactions
      establish two new carbon-carbon bonds and up to four new stereocenters. The
      silane reagents, which owe their reactivity to strain release Lewis acidity, are
      easily prepared and stable to storage.

PMID- 12207520
TI  - Self-assembling structures of long-chain phenyl glucoside influenced by the
      introduction of double bonds.
AB  - Four long-chain phenyl glucoside amphiphiles possessing a saturated or
      unsaturated long alkyl chain group as the self-assembling unit of a highly
      organized molecular architecture were synthesized. Their self-assembling
      properties were investigated by EF-TEM, SEM, CD, FT-IR, and XRD. Compound 2
      possessing one double bond in the lipophilic portion showed twisted helical
      fibers, which formed a bilayered structure with a 3.59 nm period, while compound
      3 showed the helical ribbons and left-handed nanotubular structures with 150-200
      nm inner diameters and ca. 20 nm of wall. Very interestingly, compound 4
      possessing three double bonds showed a nanotubular structure with ca. 70 nm of
      inner diameter through a helical ribbon, which formed a loose bilayered structure
      with 4.62 nm. These results indicate that self-assembling properties strongly
      depend on the number of cis double bonds.

PMID- 12207521
TI  - Synthesis and DNA binding properties of iminodiacetic acid-linked polyamides:
      characterization of cooperative extended 2:1 side-by-side parallel binding.
AB  - A series of iminodiacetic acid (IDA)-linked polyamides (DpPyPyPy-IDA-PyPyPyDp)
      were prepared and constitute polyamides joined head-to-head by a functionalizable
      five-atom linker. It was found that the IDA linker exerts a unique influence over
      the DNA binding conformation differing from both the beta-alanine (extended) or
      gamma-aminobutyric acid (hairpin) linkers, resulting in cooperative parallel side
      by-side 2:1 binding in an extended conformation most likely with a staggered
      versus stacked alignment. A generalized variant of a fluorescent intercalator
      displacement (FID) assay conducted on a series of hairpin deoxyoligonucleotides
      containing a systematically varied A/T-rich binding-site size was used to
      distinguish between the binding modes of the IDA-linked polyamides.

PMID- 12207522
TI  - A valence bond analysis of electronic degeneracies in Jahn-Teller systems: low
      lying states of the cyclopentadienyl radical and cation.
AB  - The lowest doublet electronic state of the cyclopentadienyl radical (CPDR) and
      the lowest singlet state of the cyclopentadienyl cation (CPDC) are distorted from
      the highly symmetric D(5h) structure due to the Jahn-Teller effect. A valence
      bond analysis based on the phase-change rule of Longuet-Higgins reveals that in
      both cases the distortion is due to the first-order Jahn-Teller effect. It is
      shown that, while for the radical an isolated Jahn-Teller degeneracy is expected,
      in the case of the cation the main Jahn-Teller degeneracy is accompanied by five
      satellite degeneracies. The method offers a chemically oriented way for
      identifying the distortive coordinates.

PMID- 12207524
TI  - Catalytic double-bond metathesis without the transition metal.
AB  - Iminophosphoranes of the type X(3)P=NR (X = Cl, pyrrolyl; R = alkyl, aryl)
      catalytically metathesize C=N bonds of carbodiimides via an addition/elimination
      mechanism that, despite the lack of d orbital participation in P-N bonding,
      conserves the key features of metal-catalyzed olefin metathesis.
      Diazaphosphetidine intermediates, produced by the formal [2 + 2] addition of
      carbodiimides to the P=N bond, have been isolated and characterized. All
      phosphorus-containing species in the complex catalytic reaction mixtures have
      been identified and their origins explained. The kinetics of addition of
      diisopropylcarbodiimide to Cl(3)P=NPr(i)() and subsequent elimination were
      studied, and rate constants were determined: k(add) = 1.7 x 10(-3) (+/-0.1 x 10(
      3)) M s(-1) and k(elim) = 4.0 x 10(-4) (+/-0.3 x 10(-4)) s(-1). The rate of these
      reactions corresponds well with the observed catalytic TOF of 1.44 TO/P/h.

PMID- 12207523
TI  - The origin of diastereofacial control in allylboration reactions using tartrate
      ester derived allylboronates: attractive interactions between the Lewis acid
      coordinated aldehyde carbonyl group and an ester carbonyl oxygen.
AB  - Transition-state structures for the allylboration reaction between the tartrate
      ester and tartramide modified allylboronates and acetaldehyde are located at the
      B3LYP/6-31G* level of theory. An attractive interaction between the boron
      activated aldehyde and the ester or amide carbonyl oxygen lone pair is found to
      play a major role in the favored transition states 11a and 13. This attractive
      interaction appears to be electrostatic in origin. However, an n --> pi* charge
      transfer type of interaction has not been ruled out. The distance (2.77 A)
      between the aldehydic hydrogen and the carbonyl oxygen in transition state 13 is
      beyond the sum of van der Waals radii. The formyl C-H...O bond angle (109
      degrees) in this transition structure deviates far from linearity. Therefore,
      hydrogen-bonding interactions between the formyl C-H and the amide carbonyl
      oxygen are considered negligible. The distance (3.81 A) between the aldehydic
      oxygen and the amide carbonyl oxygen in the diastereomeric, disfavored transition
      state 14 is also beyond the van der Waals radii, which suggests that n/n
      electronic repulsion plays a lesser role in stereodifferentiation in the
      allylboration reaction than originally proposed.

PMID- 12207525
TI  - Intermolecular complexes of HXeOH with water: stabilization and destabilization
      effects.
AB  - Theoretical and matrix-isolation studies of intermolecular complexes of HXeOH
      with water molecules are presented. The structures and possible decomposition
      routes of the HXeOH-(H(2)O)(n)(n = 0, 1, 2, 3) complexes are analyzed
      theoretically. It is concluded that the decay of these metastable species may
      proceed through the bent transition states (TSs), leading to the global minima on
      the respective potential energy surfaces, Xe + (H(2)O)(n+1). The respective
      barrier heights are 39.6, 26.6, 11.2, and 0.4 kcal/mol for n = 0, 1, 2, and 3.
      HXeOH in larger water clusters is computationally unstable with respect to the
      bending coordinate, representing the destabilization effect. Another
      decomposition channel of HXeOH-(H(2)O)(n), via a linear TS, leads to a direct
      break of the H-Xe bond of HXeOH. In this case, the attached water molecules
      stabilize HXeOH by strengthening the H-Xe bond. Due to the stabilization, a large
      blue shift of the H-Xe stretching mode upon complexation of HXeOH with water
      molecules is featured in calculations. On the basis of this computational result,
      the IR absorption bands at 1681 and 1742 cm(-1) observed after UV photolysis and
      annealing of multimeric H(2)O/Xe matrixes are assigned to the HXeOH-H(2)O and
      HXeOH-(H(2)O)(2) complexes. These bands are blue-shifted by 103 and 164 cm(-1)
      from the known monomeric HXeOH absorption.

PMID- 12207526
TI  - Chemical bonding variations and electron-phonon interactions.
AB  - A new functional, Psib(Phi), of an electronic state in solids based on the
      bonding indicator B(tau,tau') in terms of Mulliken's electron partitioning
      approach has been introduced. Using Psib(Phi), the bonding variations of an
      electronic state caused by electron-phonon coupling can be studied. With this
      proposed approach, the differences between the "flat band" states for Hg in
      coupling to the phonons and the peaklike structure of electron-phonon coupling
      constants in the q space are well explained.

PMID- 12207527
TI  - H-coupled electron transfer in alkane C-h activations with halogen electrophiles.
AB  - The mechanisms for the reactions of isobutane and adamantane with polyhalogen
      electrophiles (HHal(2)(+), Hal(3)(+), Hal(5)(+), and Hal(7)(+), Hal = Cl, Br, or
      I) were studied computationally at the MP2 and B3LYP levels of theory with the 6
      31G (C, H, Cl, Br) and 3-21G (I) basis sets, as well as experimentally for
      adamantane halogenations in Br(2), Br(2)/HBr, and I(+)Cl(-)/CCl(4). The
      transition structures for the activation step display almost linear C...H...Hal
      interactions and are characterized by significant charge transfer to the
      electrophile; the hydrocarbon moieties resemble the respective radical cation
      structures. The regiospecificities for polar halogenations of the 3-degree C-H
      bonds of adamantane, the high experimental kinetic isotope effects (k(H)/k(D) = 3
      4), the rate accelerations in the presence of Lewis and proton (HBr) acids, and
      the high kinetic orders for halogen (7.5 for Br(2)) can only be understood in
      terms of an H-coupled electron-transfer mechanism. The three centered-two
      electron (3c-2e) electrophilic mechanistic concept based on the attack of the
      electrophile on a C-H bond does not apply; electrophilic 3c-2e interactions
      dominate the C-H activations only with nonoxidizing electrophiles such as
      carbocations. This was shown by a comparative computational analysis of the
      electrophilic and H-coupled electron-transfer activation mechanisms for the
      isobutane reaction with an ambident electrophile, the allyl cation, at the above
      levels of theory.

PMID- 12207528
TI  - 3D TEDOR NMR experiments for the simultaneous measurement of multiple carbon
      nitrogen distances in uniformly (13)C,(15)N-labeled solids.
AB  - We describe three-dimensional magic-angle-spinning NMR experiments for the
      simultaneous measurement of multiple carbon-nitrogen distances in uniformly
      (13)C,(15)N-labeled solids. The approaches employ transferred echo double
      resonance (TEDOR) for (13)C-(15)N coherence transfer and (15)N and (13)C
      frequency labeling for site-specific resolution, and build on several previous 3D
      TEDOR techniques. The novel feature of the 3D TEDOR pulse sequences presented
      here is that they are specifically designed to circumvent the detrimental effects
      of homonuclear (13)C-(13)C J-couplings on the measurement of weak (13)C-(15)N
      dipolar couplings. In particular, homonuclear J-couplings lead to two undesirable
      effects: (i) they generate anti-phase and multiple-quantum (MQ) spin coherences,
      which lead to spurious cross-peaks and phase-twisted lines in the 2D (15)N-(13)C
      correlation spectra, and thus degrade the spectral resolution and prohibit the
      extraction of reliable cross-peak intensities, and (ii) they significantly reduce
      cross-peak intensities for strongly J-coupled (13)C sites (e.g., CO and
      C(alpha)). The first experiment employs z-filter periods to suppress the anti
      phase and MQ coherences and generates 2D spectra with purely absorptive peaks for
      all TEDOR mixing times. The second approach uses band-selective (13)C pulses to
      refocus J-couplings between (13)C spins within the selective pulse bandwidth and
      (13)C spins outside the bandwidth. The internuclear distances are extracted by
      using a simple analytical model, which accounts explicitly for multiple spin-spin
      couplings contributing to cross-peak buildup. The experiments are demonstrated in
      two U-(13)C,(15)N-labeled peptides, N-acetyl-L-Val-L-Leu (N-ac-VL) and N-formyl-L
      Met-L-Leu-L-Phe (N-f-MLF), where 20 and 26 (13)C-(15)N distances up to
      approximately 5-6 A were measured, respectively. Of the measured distances, 10 in
      N-ac-VL and 13 in N-f-MLF are greater than 3 A and provide valuable structural
      constraints.

PMID- 12207529
TI  - An NMR experiment for the accurate measurement of heteronuclear spin-lock
      relaxation rates.
AB  - Rotating-frame relaxation rates, R(1)(rho), are often measured in NMR studies of
      protein dynamics. We show here that large systematic errors can be introduced
      into measured values of heteronuclear R(1)(rho) rates using schemes which are
      usually employed to suppress cross-correlation between dipole-dipole and CSA
      relaxation mechanisms. For example, in a scalar-coupled two-spin X-H spin system
      the use of (1)H WALTZ16 decoupling or (1)H pulses applied at regularly spaced
      intervals leads to a significant overestimation of heteronuclear R(1)(rho)
      values. The problem is studied experimentally and theoretically for (15)N-(1)H
      and (13)C-(1)H spin pairs, and simple schemes are described which eliminate the
      artifacts. The approaches suggested are essential replacements of existing
      methodology if accurate dynamics parameters are to be extracted from spin-lock
      relaxation data sets.

PMID- 12207530
TI  - Charge-transfer phenomena in novel, dual-component, sugar-based organogels.
AB  - The synthesis of a new saccharide-based gelator (2) containing a donor moiety has
      been described. Gelation experiments of a dual-component gel consisting of a
      saccharide-based gelator bearing an acceptor group (1) and of 2 have been
      performed in a variety of organic solvents and water. Moreover, gelation tests at
      different molar ratios of 1 and 2 have been performed in water, octanol, and
      diphenyl ether. In these last two solvents a gel color change was observed, from
      colorless to yellow, upon cooling of the sample to room temperature. This
      phenomenon was further investigated by UV-visible spectroscopy, which revealed
      the presence of charge-transfer interactions in the gel, in octanol. Temperature
      dependence UV spectroscopy confirmed that such interactions occur in the gel but
      not in the corresponding solution sample. Furthermore, T(gel) measurements show
      that dual-component gels of 1 and 2 present increased thermal stability at a
      50:50 ratio of the two gelators, in dependence of the solvent. Transmission
      electron microscopy (TEM) images of the single-component gels in diphenyl ether
      revealed that they consist of a fibrous network, while the dual-component gel
      presents a novel, helical, fibrous-bundle structure.

PMID- 12207531
TI  - Mechanism of the double aldol reaction: the first spectroscopic characterization
      of a carbon-bound boron enolate derived from carboxylic esters.
AB  - The novel doubly borylated enolate is identified as an intermediate of the double
      aldol reaction of acetate esters. As a precursor to the formation of the doubly
      borylated enolate, carbon-bound boron enolates of carboxylic esters are
      spectroscopically characterized for the first time. When 2,6-diisopropylphenyl
      acetate (10d) is treated with c-Hex(2)BOTf (1.3 equiv) and triethylamine (1.5
      equiv) in CDCl(3), the corresponding mono-enolate is formed as a mixture of
      oxygen- (11d) and carbon-bound (12d) forms in 71% and 20% yields, respectively.
      The structures of these enolates have been unambiguously determined by NMR
      spectroscopy. Investigation of the enolization of a series of substituted aryl
      acetates shows that the steric factor of the acetate affects the degree of the
      mono-enolate (as a mixture of oxygen- and carbon-bound enolates) and the doubly
      borylated enolate formation. Studies also revealed that oxygen- and carbon-bound
      boron enolates exist as equilibrium mixtures and that a proton transfer process
      occurs between oxygen- and carbon-bound enolates. The doubly borylated enolate
      formation is general for a variety of carbonyl compounds. Besides acetate esters,
      carbonyl containing compounds, such as acetic acid, dimethylacetamide,
      methoxyacetone, and 3-acetyl-2-oxazolidinone, also produce the doubly borylated
      enolates when treated with c-Hex(2)BOTf (2.5 equiv) and triethylamine (3.0
      equiv). A plausible pathway of the double aldol reaction involving a carbon-bound
      boron enolate as a key intermediate is proposed.

PMID- 12207532
TI  - 5-Endo-trig radical cyclizations: disfavored or favored processes?
AB  - Relative kinetic data were determined for the 5-endo-trig cyclization of radical
      12 compared to hydrogen abstraction from (TMS)(3)SiH in the temperature range of
      344-430 K, which allows for the estimation of a rate constant of 2 x 10(4) s(
      )(1) at 298 K with an activation energy of ca. 9 kcal/mol for the cyclization
      process. The 5-endo-trig cyclization of a variety of radicals that afford five
      membered nitrogen-containing heterocycles was addressed computationally at the
      UB3LYP/6-31G level. The 5-endo vs 4-exo mode of cyclication and the effect of
      delocalization of the unpaired electron in the transition state were
      investigated. Because the ring formed during cyclization contains five sp(2)
      centers, electrocyclization via a pentadienyl-like resonance form was also
      considered. For comparison, similar calculations were performed for 4-penten-1-yl
      and related radicals. The factors that affect the activation energies of
      homolytic 5-endo-trig cyclization were determined. In the absence of steric or
      conformational effects, the endo cyclization to form the five-membered ring was
      strongly favored over exo cyclization to form the four-membered ring not only on
      thermodynamic grounds but also kinetically. When a substituent on the double bond
      was able to delocalize the unpaired electron in the transition state of the 4-exo
      path, the two modes of cyclization became kinetically comparable. These results
      have an important bearing on the generalization of the Baldwin-Beckwith rules,
      which classified the 5-endo-trig radical cyclization as a "disfavored" process.

PMID- 12207533
TI  - The chemistry of amine-azide interconversion: catalytic diazotransfer and
      regioselective azide reduction.
AB  - Azides have proven to be useful precursors to amines in organic syntheses. This
      report describes an improvement of the diazotransfer reaction and the first
      example of a regioselective azide reduction of compounds containing multiple
      azides. The use of a specific ratio of solvents and zinc chloride as a catalyst
      resulted in a more efficient diazotransfer reaction capable of delivering >90%
      conversion per amine with shorter reaction times than those previously reported.
      Azides can be reduced with good regioselectivity in moderate yields by a
      modification of the Staudinger reaction using trimethylphosphine at low
      temperatures. Electronic factors determine the selectivity for azide reduction,
      and the reaction is predictable by NMR analysis of the starting material. Several
      examples for the diazotransfer and regioselective azide reduction reactions are
      given, and a mechanistic hypothesis for both is proposed.

PMID- 12207534
TI  - Enhancement of enantioselectivity by THF in asymmetric mo-catalyzed olefin
      metathesis. Catalytic enantioselective synthesis of cyclic tertiary ethers and
      spirocycles.
AB  - Mo-catalyzed enantioselective rearrangement of achiral cyclopentenyl tertiary
      ethers to chiral cyclohexenyl tertiary ethers are reported. These olefin
      metathesis transformations proceed efficiently and with high levels of
      enantioselectivity. A noteworthy feature of these reactions is that added
      tetrahydrofuran exerts a remarkably positive influence on the enantioselectivity
      of the metathesis-based rearrangement. The first examples of catalytic asymmetric
      synthesis of spirocyclic structures by enantioselective olefin metathesis are
      also disclosed.

PMID- 12207536
TI  - Combined computational and experimental study of substituent effects on the
      thermodynamics of H(2), CO, arene, and alkane addition to iridium.
AB  - The thermodynamics of small-molecule (H(2), arene, alkane, and CO) addition to
      pincer-ligated iridium complexes of several different configurations (three
      coordinate d(8), four-coordinate d(8), and five-coordinate d(6)) have been
      investigated by computational and experimental means. The substituent para to the
      iridium (Y) has been varied in complexes containing the (Y-PCP)Ir unit (Y-PCP =
      eta(3)-1,3,5-C(6)H(2)[CH(2)PR(2)](2)Y; R = methyl for computations; R = tert
      butyl for experiments); substituent effects have been studied for the addition of
      H(2), C-H, and CO to the complexes (Y-PCP)Ir, (Y-PCP)Ir(CO), and (Y-PCP)Ir(H)(2).
      Para substituents on arenes undergoing C-H bond addition to (PCP)Ir or to
      (PCP)Ir(CO) have also been varied computationally and experimentally. In general,
      increasing electron donation by the substituent Y in the 16-electron complexes,
      (Y-PCP)Ir(CO) or (Y-PCP)Ir(H)(2), disfavors addition of H-H or C-H bonds, in
      contradiction to the idea of such additions being oxidative. Addition of CO to
      the same 16-electron complexes is also disfavored by increased electron donation
      from Y. By contrast, addition of H-H and C-H bonds or CO to the three-coordinate
      parent species (Y-PCP)Ir is favored by increased electron donation. In general,
      the effects of varying Y are markedly similar for H(2), C-H, and CO addition. The
      trends can be fully rationalized in terms of simple molecular orbital
      interactions but not in terms of concepts related to oxidation, such as charge
      transfer or electronegativity differences.

PMID- 12207535
TI  - Synthesis of isotopically labeled arachidonic acids to probe the reaction
      mechanism of prostaglandin H synthase.
AB  - Prostaglandin H synthase (PGHS) catalyzes the conversion of arachidonic acid to
      prostaglandin G(2) in the cyclooxygenase reaction. The first step of the
      mechanism has been proposed to involve abstraction of the pro-S hydrogen atom
      from C13 to generate a pentadienyl radical spanning C11-C15. We report here the
      synthesis of six site-specifically deuterated arachidonic acids to investigate
      the structure of the radical intermediate. The preparation of these compounds was
      achieved using a divergent scheme that involved one advanced intermediate for all
      targets. The synthetic design introduced the label late in the routes and allowed
      the utilization of common synthetic intermediates in the preparation of various
      targets. Both 13(R)- and 13(S)-deuterium-labeled arachidonic acids were
      synthesized in high enantiomeric purity as deduced from soybean lipoxygenase
      assays and mass spectrometric analysis of the resulting enzymatic products. Each
      synthetic compound was reacted under anaerobic conditions with the wide singlet
      tyrosyl radical of PGHS-2 to generate a radical intermediate that was analyzed by
      EPR. Deuterium substitution at positions 11, 13(S), and 15 resulted in the loss
      of one hyperfine interaction, indicating that the protons at these positions
      interact with the unpaired electron. Simulation of the spectra was achieved with
      one set of parameters that are consistent with the assignment of a pentadienyl
      radical. Use of 16-[(2)H(2)]-arachidonic acid indicated that only one of the
      protons at C16 gives rise to a strong hyperfine interaction. The findings are
      discussed in the context of two proposed mechanisms for the cyclooxygenase
      reaction.

PMID- 12207537
TI  - Electronic structure and reactivity of low-spin Fe(III)-hydroperoxo complexes:
      comparison to activated bleomycin.
AB  - The spectroscopic properties, electronic structure, and reactivity of the low
      spin Fe(III)-hydroperoxo complex [Fe(N4Py)(OOH)](2+) (1, N4Py = N,N-bis(2
      pyridylmethyl)-N-bis(2-pyridyl)methylamine) are investigated in comparison to
      those of activated bleomycin (ABLM). Complex 1 is characterized by Raman features
      at 632 (Fe-O stretch) and 790 cm(-1) (O-O stretch), corresponding to a strong Fe
      O bond (force constant 3.62 mdyn/A) and a weak O-O bond (3.05 mdyn/A). The UV-vis
      spectrum of 1 shows a broad absorption band around 550 nm that is assigned to a
      charge-transfer transition from the hydroperoxo to a t(2g) d orbital of Fe(III)
      using resonance Raman and MCD spectroscopies and density functional (DFT)
      calculations. Compared to low-spin [Fe(TPA)(OH(x))(OO(t)Bu)](x+)(TPA = tris(2
      pyridylmethyl)amine, x = 1 or 2), an overall similar Fe-OOR bonding results for
      low-spin Fe(III)-alkylperoxo and -hydroperoxo species. Correspondingly, both
      systems show similar reactivities and undergo homolytic cleavage of the O-O bond.
      From the DFT calculations, this reaction is more endothermic for 1 due to the
      reduced stabilization of the .OH radical compared to .O(t)Bu and the absence of
      the hydroxo ligand that helps to stabilize the resulting Fe(IV)=O species. In
      contrast, ABLM has a somewhat different electronic structure where no pi donor
      bond between the hydroperoxo ligand and iron(III) is present [Neese, F.; Zaleski,
      J. M.; Loeb-Zaleski, K.; Solomon, E. I. J. Am. Chem. Soc. 2000, 122, 11703].
      Possible reaction pathways for ABLM are discussed in relation to known
      experimental results.

PMID- 12207538
TI  - Inter- and intramolecular spin transfer in molecular magnetic materials. Solid
      state NMR spectroscopy of paramagnetic metallocenium ions.
AB  - To shed light on the interaction in molecule-based magnetic materials, the
      decamethylmetallocenium hexafluorophosphates, [(C(5)Me(5))(2)M](+) [PF(6)](-)
      with M = Cr, Mn, Fe, Co, and Ni, as well as the tetracyanoethenides,
      [(C(5)Me(5))(2)M](+) [TCNE](-) with M = Cr, Mn, Fe, and Co, have been
      investigated in the solid state by using (1)H, (13)C, (19)F, and (31)P NMR
      spectroscopy under magic angle spinning (MAS). The isotropic (13)C and (1)H NMR
      signals cover ranges of about 1300 and 500 ppm, respectively. From the shift
      anisotropies of the ring carbon signal of the [(C(5)Me(5))(2)M](+) cations, the
      total unpaired electron spin density in the ligand pi orbitals has been
      calculated; it amounts up to 36% (M = Ni) and is negative for M = Cr, Mn, and Fe.
      The radical anion of [(C(5)Me(5))(2)M](+) [TCNE](-) shifts the (13)C NMR signals
      of all [(C(5)Me(5))(2)M](+) cations to high frequency, which establishes transfer
      of positive spin density from the anions to the cations. The (19)F and (31)P NMR
      signals of the paramagnetic salts [(C(5)Me(5))(2)M](+) [PF(6)](-) are shifted up
      to 13.5 ppm relative to diamagnetic [(C(5)Me(5))(2)Co](+) [PF(6)](-). The signs
      of these shifts are the same as those of the pi spin density in
      [(C(5)Me(5))(2)M](+). After consideration of interionic ligand- and metal
      centered dipolar shifts, this establishes cation-anion spin delocalization. The
      mixed crystals [(C(5)Me(5))(2)M(x)Co(1-x)](+)[PF(6)](-) have been prepared for M
      = Cr and Ni. They are isostructural with [(C(5)Me(5))(2)Co](+) [PF(6)](-) whose
      single-crystal structure has been determined by X-ray diffraction. The (13)C,
      (19)F, and (31)P MAS NMR spectra of the mixed crystals show that the respective
      two closest paramagnetic ions in the lattice delocalize spin density to
      [(C(5)Me(5))(2)Co](+), [(C(5)Me(5))(2)Ni](+), and [PF(6)](-). In
      [(C(5)Me(5))(2)M](+), about 10(-4) au per carbon atom are transferred.

PMID- 12207539
TI  - Spectroscopic and computational studies on iron and manganese superoxide
      dismutases: nature of the chemical events associated with active-site pKs.
AB  - A combined spectroscopic/computational approach has been utilized to explore the
      chemical origins of the active-site pKs of the structurally homologous Fe- and Mn
      dependent superoxide dismutases (SODs). Absorption, circular dichroism, magnetic
      circular dichroism, and variable-temperature, variable-field magnetic circular
      dichroism spectroscopic experiments have permitted us to determine electronic
      transition energies and polarizations, as well as ground-state spin Hamiltonian
      parameters. These experimental data have been used in conjunction with
      semiempirical intermediate neglect of differential overlap/spectroscopic
      parametrization configuration interaction (INDO/S-CI) computations for evaluating
      hypothetical active-site models for the high-pH species generated by density
      functional theory (DFT) geometry optimizations. Our experimental and
      computational data indicate that both reduced FeSOD and oxidized MnSOD do not
      bind hydroxide at high pH; rather, the active-site pK for these two species is
      attributed to deprotonation of a second-sphere tyrosine. Conversely, our data
      obtained on oxidized FeSOD indicate that hydroxide binding is responsible for the
      observed active-site pK for this species. Intriguingly, in the Fe-substituted
      form of MnSOD this identical chemical event occurs at a significantly lower pH.
      Overall, our results suggest an important role for second-sphere amino acids in
      tuning the active sites' interaction with small anions and bring into question
      the assumption that these homologous enzymes operate by the same molecular
      mechanism.

PMID- 12207540
TI  - Ab initio studies on Al(+)(H(2)O)(n), HAlOH(+)(H(2)O)(n-1), and the size
      dependent H(2) elimination reaction.
AB  - We report computational studies on Al(+)(H(2)O)(n), and HAlOH(+)(H(2)O)(n-1), n =
      6-14, by the density functional theory based ab initio molecular dynamics method,
      employing a planewave basis set with pseudopotentials, and also by conventional
      methods with Gaussian basis sets. The mechanism for the intracluster H(2)
      elimination reaction is explored. First, a new size-dependent insertion reaction
      for the transformation of Al(+)(H(2)O)(n), into HAlOH(+)(H(2)O)(n-1) is
      discovered for n > or = 8. This is because of the presence of a fairly stable six
      water-ring structure in Al(+)(H(2)O)(n) with 12 members, including the Al(+).
      This structure promotes acidic dissociation and, for n > or = 8, leads to the
      insertion reaction. Gaussian based BPW91 and MP2 calculations with 6-31G* and 6
      31G** basis sets confirmed the existence of such structures and located the
      transition structures for the insertion reaction. The calculated transition
      barrier is 10.0 kcal/mol for n = 9 and 7.1 kcal/mol for n = 8 at the MP2/6-31G**
      level, with zero-point energy corrections. Second, the experimentally observed
      size-dependent H(2) elimination reaction is related to the conformation of
      HAlOH(+)(H(2)O)(n-1), instead of Al(+)(H(2)O)(n). As n increases from 6 to 14,
      the structure of the HAlOH(+)(H(2)O)(n-1) cluster changes into a caged structure,
      with the Al-H bond buried inside, and protons produced in acidic dissociation
      could then travel through the H(2)O network to the vicinity of the Al-H bond and
      react with the hydride H to produce H(2). The structural transformation is
      completed at n = 13, coincident approximately with the onset of the H(2)
      elimination reaction. From constrained ab initio MD simulations, we estimated the
      free energy barrier for the H(2) elimination reaction to be 0.7 eV (16 kcal/mol)
      at n = 13, 1.5 eV (35 kcal/mol) at n = 12, and 4.5 eV (100 kcal/mol) at n = 8.
      The existence of transition structures for the H(2) elimination has also been
      verified by ab initio calculations at the MP2/6-31G** level. Finally, the switch
      off of the H(2) elimination for n > 24 is explored and attributed to the
      diffusion of protons through enlarged hydrogen bonded H(2)O networks, which
      reduces the probability of finding a proton near the Al-H bond.

PMID- 12207541
TI  - Rapid excited-state structural reorganization captured by pulsed X-rays.
AB  - Visible light excitation of [Cu(I)(dmp)(2)](BArF), where dmp is 2,9-dimethyl-1,10
      phenanthroline and BArF is tetrakis(3,5-bis(trifluoromethylphenyl))borate, in
      toluene produces a photoluminescent, metal-to-ligand charge-transfer (MLCT)
      excited state with a lifetime of 98 +/- 5 ns. Probing this state within 14 ns
      after photoexcitation with pulsed X-rays establishes that a Cu(II) center, borne
      in a Cu(I) geometry, binds an additional ligand to form a five-coordinate complex
      with increased bond lengths and a coordination geometry of distorted trigonal
      bipyramid. The average Cu-N bond length increases in the excited state by 0.07 A.
      The transiently formed five-coordinate MLCT state is photoluminescent under the
      condition studied, indicating that the absorptive and emissive states have
      distinct geometries. The data represent the first X-ray characterization of a
      molecular excited state in fluid solution on a nanosecond time scale.

PMID- 12207542
TI  - Theoretical and experimental investigation of the effect of proton transfer on
      the (27)al MAS NMR line shapes of zeolite-adsorbate complexes: an independent
      measure of solid Acid strength.
AB  - Assessing the degree of proton transfer from a Bronsted acid site to one or more
      adsorbed bases is central to arguments regarding the strength of zeolites and
      other solid acids. In this regard certain solid-state NMR measurements have been
      fruitful; for example, some (13)C, (15)N, or (31)P resonances of adsorbed bases
      are sensitive to protonation, and the (1)H chemical shift of the Bronsted site
      itself reflects hydrogen bonding. We modeled theoretically the structures of
      adsorption complexes of several bases on zeolite HZSM-5, calculated the
      quadrupole coupling constants (Q(cc)) and asymmetry parameters (eta) for aluminum
      in these complexes and then in turn simulated the central transitions of their
      (27)Al MAS NMR spectra. The theoretical line width decreased monotonically with
      the degree of proton transfer, reflecting structural relaxation around aluminum
      as the proton was transferred to a base. We verified this experimentally for a
      series of adsorbed bases by way of single-pulse MAS and triple quantum MQMAS
      (27)Al NMR. The combined theoretical and experimental approach described here
      provides a strategy by which (27)Al data can be applied to resolve disputed
      interpretations of proton transfer based on other evidence.

PMID- 12207543
TI  - Rigid dendritic donor-acceptor ensembles: control over energy and electron
      transduction.
AB  - Several generations of phenylenevinylene dendrons, covalently attached to a C(60)
      core, have been developed as synthetic model systems with hierarchical, fine
      tuned architectures. End-capping of these dendritic spacers with dibutylaniline
      or dodecyloxynaphthalene, as antennas/electron donors, yielded new donor-bridge
      acceptor ensembles in which one, two, or four donors are allocated at the
      peripheral positions of the well-defined dendrons, while the electron accepting
      fullerene is placed at the focal point of the dendron. On the basis of our cyclic
      voltammetry experiments, which disclose a single anodic oxidation and several
      cathodic reduction processes, we rule out significant, long-range couplings
      between the fullerene core and the end-standing donors in their ground-state
      configuration. Photophysical investigations, on the other hand, show that upon
      photoexcitation an efficient and rapid transfer of singlet excited-state energy
      (6 x 10(10) to 2.5 x 10(12) s(-1)) controls the reactivity of the initially
      excited antenna portion. Spectroscopic and kinetic evidence suggests that yet a
      second contribution, that is, an intramolecular electron-transfer, exists,
      affording C(60)(.-) -dendron(.+) with quantum yields (Phi) as high as 0.76 and
      lifetimes (tau) that are on the order of hundreds of nanoseconds (220-725 ns).
      Variation of the energy gap modulates the interplay of these two pathways (i.e.,
      competition or sequence between energy and electron transfer).

PMID- 12207544
TI  - Estimates of the ab initio limit for pi-pi interactions: the benzene dimer.
AB  - State-of-the-art electronic structure methods have been applied to the simplest
      prototype of aromatic pi-pi interactions, the benzene dimer. By comparison to
      results with a large aug-cc-pVTZ basis set, we demonstrate that more modest basis
      sets such as aug-cc-pVDZ are sufficient for geometry optimizations of
      intermolecular parameters at the second-order Moller-Plesset perturbation theory
      (MP2) level. However, basis sets even larger than aug-cc-pVTZ are important for
      accurate binding energies. The complete basis set MP2 binding energies, estimated
      by explicitly correlated MP2-R12/A techniques, are significantly larger in
      magnitude than previous estimates. When corrected for higher-order correlation
      effects via coupled cluster with singles, doubles, and perturbative triples
      [CCSD(T)], the binding energies D(e) (D(0)) for the sandwich, T-shaped, and
      parallel-displaced configurations are found to be 1.8 (2.0), 2.7 (2.4), and 2.8
      (2.7) kcal mol(-1), respectively.

PMID- 12207545
TI  - In situ raman spectroelectrochemistry of electron transfer between glassy carbon
      and a chemisorbed nitroazobenzene monolayer.
AB  - In situ Raman spectroscopy was used to monitor 4-nitroazobenzene (NAB) in an
      electrochemical cell, both as a free molecule and as a chemisorbed monolayer on a
      glassy carbon (GC) electrode surface. Reduction of free NAB exhibited two well
      defined voltammetric couples in acetonitrile, and the accompanying spectral
      changes supported a mechanism involving two successive 1-e(-) transfers. Raman
      spectra of NAB chemisorbed to GC via diazonium ion reduction were obtained in
      acetonitrile with a high-sensitivity, line-focused CCD spectrometer. The
      chemisorbed NAB spectra were quite different from the free NAB spectra, and were
      sufficiently strong to monitor as a function of applied potential. In the
      potential range of +400 to -800 mV vs Ag/Ag(+), the intensity of the Raman bands
      associated with the phenyl-NO(2) moiety varied, implying an electronic
      interaction between the pi system of the graphitic substrate and the chemisorbed
      NAB molecules. Negative of -800 mV, a 1-e(-) voltammetric reduction peak was
      observed, which was reversible on the positive voltage scan. This peak was
      accompanied by significant spectral changes, particularly the loss of the N=N and
      NO(2) stretches. The spectra are consistent with formation of a quinoid structure
      containing a C=C double bond between the NAB and the graphitic surface. The
      electron transfer and spectral changes occurred over a wider potential range than
      expected for a conventional Nernstian equilibrium, but did not appear to be
      broadened by slow electron-transfer kinetics. The results imply a significant
      perturbation of electron transfer between the GC and the monolayer, caused by
      strong electronic coupling between the graphitic pi system and the NAB orbitals.
      Rather than a discrete electron transfer to a free molecule, the electron
      transfer to chemisorbed NAB is more gradual, and is presumably driven by the
      electric field at the electrode/solution interface.

PMID- 12207546
TI  - Dianionic tetraborates do exist as stable entities.
AB  - To date, B(6)H(6)(2-) and some of its derivatives are the smallest members of the
      closo-borates that have been synthesized and analyzed in condensed phases. In
      contrast, no stable dianionic tetraborate has yet been observed, either in
      solution or solids or in the gas phase. In this work, the gas-phase stability of
      dianionic tetraborates B(4)X(4)(2-) (X = H, CN, NC, or BO) is investigated with
      ab initio methods. For this objective, the geometries of the dianions are
      optimized, the electronic stability is tested, and various fragmentation channels
      are studied. In agreement with previous examinations, tetrahedral isomers of all
      examined tetraborates have been found to represent geometrically stable isomers
      and to exhibit a triplet electronic ground state. However, these isomers are
      electronically unstable, i.e., their additional electrons are not bound.
      Furthermore, new D(2)(d)()-symmetric isomers of B(4)X(4)(2-) (X = H, CN, NC, or
      BO) have been identified that have a closed-shell singlet ground state and are
      lower in energy than their tetrahedral counterparts. Moreover, B(4)(CN)(4)(2-)
      and B(4)(BO)(4)(2-) represent stable gas-phase dianions and are predicted to be
      observable in suitable experiments. The electronic properties and geometries of
      these dianions are discussed in detail and explained in terms of the
      electrostatic repulsion of the excess electrons and the aromaticity of the
      dianions.

PMID- 12207547
TI  - Exploring the capabilities of X-ray absorption spectroscopy for determining the
      structure of electrolyte solutions: computed spectra for Cr(3+) or Rh(3+) in
      water based on molecular dynamics.
AB  - Extended X-ray absorption fine structure (EXAFS) spectra of Cr(3+) and Rh(3+) in
      aqueous solution are analyzed and compared with computed spectra derived from
      structural results obtained by molecular dynamics (MD) simulation. This procedure
      quantifies the reliability of the EXAFS structural determination when applied to
      ions in solution. It provides guidelines for interpreting experimental spectra of
      octahedrally coordinated metal cations in aqueous solution. A set of
      relationships among Debye-Waller factors is proposed on the basis of MD results
      to reduce the number of independent fit parameters. The determination of the
      second hydration shell is examined. Calculated XANES spectra compare well with
      experimental ones. Indeed, the splitting observed on the main peak of the Rh K
      edge was anticipated by the calculations. Simulated spectra from MD structures of
      increasing cluster size show a relationship between the second hydration shell
      and features of the XANES region at energies just above the edge. The combination
      of quantum and statistical calculations with the XANES spectrum is found to be
      very fruitful to get insight into the quantitative estimation of structural
      properties of electrolyte solutions.

PMID- 12207548
TI  - Acetate binding at the photosystem II oxygen evolving complex: an S(2)-state
      multiline signal ESEEM study.
AB  - Previously, using acetate deuterated in the methyl hydrogen positions, we showed
      that acetate binds in close proximity to the Mn cluster/Y(.)(z) tyrosine dual
      spin complex in acetate-inhibited photosystem II (PSII) preparations exhibiting
      the "split" EPR signal arising from the S(2)-Y(.)(z) interaction [Force, D. A.;
      Randall, D. W.; Britt, R. D. Biochemistry 1997, 36, 12062-12070]. By using
      paramagnetic NO to quench the paramagnetism of Y(.)(z), we are able to observe
      the ESEEM spectrum of deuterated acetate interacting with only the Mn cluster. A
      good fit of the ESEEM data indicates two (2)H dipolar hyperfine couplings of
      0.097 MHz and one of 0.190 MHz. Modeling of these dipolar interactions, using our
      "dangler" 3 + 1 model for the S(2)-state of the Mn cluster, reveals distances
      consistent with direct ligation of acetate to the Mn cluster. As acetate
      inhibition is competitive with the essential cofactor Cl(-), this suggests that
      Cl(-) ligates directly to the Mn cluster. The effect of acetate binding on the
      structure of the Mn cluster is investigated by comparing the Mn-histidine
      coupling in NO/acetate-treated PSII and untreated PSII using ESEEM. We find that
      the addition of acetate and NO does not affect the histidine ligation to the Mn
      cluster. We also investigate the ability of acetate to access Y(.)(z) in Mn
      depleted PSII, a PSII preparation expected to be more solvent accessible than
      intact PSII. We detect no coupling between Y(.)(z) and acetate. We have
      previously shown that small alcohols such as methanol can ligate to the Mn
      cluster with ease, while larger alcohols such as 2-propanol, as well as DMSO, are
      excluded [Force, D. A.; Randall, D. W.; Lorigan, G. A.; Clemens, K. L.; Britt, R.
      D. J. Am. Chem. Soc. 1998, 120, 13321-13333]. We probe the effect of acetate
      binding on the ability of methanol and DMSO to bind to the Mn cluster. We find
      that methanol is able to bind to the Mn cluster in the presence of acetate. We
      detect no DMSO binding in the presence of acetate. Thus, acetate binding does not
      increase the affinity or accessibility for DMSO binding at the Mn cluster. We
      also explore the possibility that the acetate binding site is also a binding site
      for substrate water. By comparing the ratioed three-pulse ESEEM spectra of a
      control, untreated PSII sample in 50% D(2)O to an NO/acetate-treated PSII sample
      in 50% D(2)O, we find that the binding of acetate to the oxygen evolving complex
      of photosystem II displaces deuterons bound very closely to the Mn cluster.

PMID- 12207549
TI  - Gene therapy for renal disorders: what are the benefits for the elderly?
AB  - Chronic renal failure is one of the major health problems for the elderly.
      Currently, about 50% of all patients receiving chronic dialysis for end-stage
      renal disease (ESRD) are aged 65 years or older. Their first-year mortality rate
      is as high as 30%. The leading causes of ESRD in the elderly are diabetic
      nephropathy, hypertension and large vessel diseases, and glomerulonephritis. The
      elderly are also prone to developing acute renal failure induced by ischaemic
      injury or nephrotoxic drugs. Gene transfer in experimental animals have been
      tested in all of these conditions, as well as in animal kidney transplantation
      models, with various degrees of success. However, there are many obstacles to be
      overcome before gene therapy can be tested clinically for renal disorders. In
      particular, the major challenges include determining how to prolong and control
      transgene expression or antisense inhibition and how to minimise the adverse
      effects of viral or nonviral vectors. Once these problems are solved, gene
      therapy will have a role in treating age-related renal impairment.

PMID- 12207550
TI  - Potential of transdermal drug delivery in Parkinson's disease.
AB  - There has been a growing recognition that pulsatile stimulation of dopamine
      receptors may be an important mechanism in the generation of the motor
      fluctuations that often develop and compromise the effectiveness of long-term
      levodopa administration in persons with Parkinson's disease (PD). This has
      prompted investigation of treatment approaches that might provide more constant,
      and therefore physiological, dopamine receptor stimulation. Frequent levodopa
      administration, controlled-release levodopa preparations, inhibitors of levodopa
      metabolism, and duodenal, subcutaneous and even intravenous infusions of levodopa
      or dopamine agonists have all been employed with this goal in mind, but all have
      limitations. Transdermal drug delivery is a treatment approach that is not only
      capable of providing a constant rate of drug delivery, but is also non-invasive
      and relatively simple to use. However, developing a drug to be delivered
      transdermally for the treatment of PD has been anything but easy. Levodopa and
      many dopamine agonists are not sufficiently soluble to be administered via the
      transdermal route, and blind alleys have been encountered thus far in the
      investigation of suitably soluble drugs. Nevertheless, investigation continues
      and yet another candidate drug, rotigotine (N-0923), is currently under active
      investigation. Techniques designed to enhance skin permeation and thus improve
      the effectiveness of transdermal drug delivery are also potential sources for
      future treatment advances.

PMID- 12207551
TI  - Acute myeloid leukaemia: optimising treatment in elderly patients.
AB  - Acute myeloid leukaemia (AML) is a disease of the elderly (median age at
      presentation 64 years). The outcome in older patients with AML is much worse than
      that for similarly treated younger patients. Older patients have a high incidence
      of recognised poor prognostic features (poor performance status, unfavourable
      cytogenetics, CD34 positive phenotype, raised serum lactate dehydrogenase levels
      and increased incidence of multidrug resistance protein expression). In addition,
      treatment is less well tolerated as there is an increased incidence of
      comorbidity in the elderly. The outlook for most patients is poor (4% survival at
      5 years). However, it is possible to select a group of patients who are fit, with
      no pre-existing problems and good performance status who will respond well to
      intensive chemotherapy, and these patients should be treated aggressively. Less
      intensive treatment is probably more suitable for patients not fitting these
      criteria. Patients and their relatives should be counselled appropriately as to
      the prognosis of AML, the choices of treatment available and that intensive
      regimens are not an appropriate choice for many patients.

PMID- 12207552
TI  - Relapse prevention and maintaining abstinence in older adults with alcohol-use
      disorders.
AB  - Although older adults are sometimes believed to have the lowest rates of alcohol
      abuse as an age cohort, the prevalence of alcohol use and abuse in this group is
      clearly underestimated. The under-diagnosis of alcohol abuse is due, in part, to
      the facts that the effects of alcohol use among older adults tend to be less
      clearly visible than among other age groups and that older adults are less likely
      to seek treatment than younger age groups. An additional challenge to diagnosis
      may be a lack of previous alcohol abuse by the patient, as approximately one
      third of older adults with alcohol-use problems first develop their drinking
      problem after the age of 60 years. With a demographic shift that is expected to
      increase the number of older adults with alcohol problems, the awareness and
      understanding of this problem becomes increasingly important. Under-diagnosis of
      problem drinking in older adults is particularly unfortunate because the risks
      associated with alcohol abuse and relapse for the elderly are significant.
      Relapse, or the return to drinking following abstinence, may follow situations
      that are of particularly high risk for older adults. These include situations
      related to anxiety, interpersonal conflict, depression, loneliness, loss or
      social isolation. By helping patients to monitor these high-risk situations, to
      identify strategies that have been successful in promoting abstinence in the
      past, and to become engaged in treatment, relapse may be avoided and abstinence
      maintained. Treatments such as cognitive-behavioural therapy, group and family
      therapies and self-help groups are just as effective for older adults as they are
      for other age groups. In fact, group and family therapies and self-help groups
      may be of particular benefit to older adults because of the emphasis on social
      support. Medicinal adjuncts are also equally effective in the elderly, but strict
      compliance and careful monitoring of adverse effects are especially important in
      patients who take multiple medications. Because of their benign adverse effect
      profiles, naltrexone and acamprosate are particularly good pharmacological agents
      for relapse prevention in older adults.

PMID- 12207553
TI  - Outcomes of lipid-lowering treatment in postmenopausal women.
AB  - Elevated triglycerides and low high-density lipoprotein (HDL) levels are more
      important coronary risk factors in women, and elevated low-density lipoprotein
      (LDL) levels less important in women, than men. There is clear-cut evidence in
      clinical trials that the benefit of cholesterol lowering in women and men is
      virtually identical. Modifiers of lipids and lipoproteins in women include
      diabetes mellitus, bodyweight and its distribution, and menopausal status.
      Diabetes is a more powerful predictor of risk in women than men. This may relate
      to the importance of elevated triglycerides as a risk factor in women, and to the
      effects of lipoprotein glycosylation, which lead to increased susceptibility to
      arterial deposition of LDL and decreased reverse cholesterol transport with HDL.
      Therapy for lipoprotein disorders in women and men is identical. For the
      overwhelming majority of patients, treatment with statin therapy is both highly
      efficacious and well tolerated.

PMID- 12207555
TI  - Complexity and non-linear description of diurnal cortisol and growth hormone
      secretory patterns before and after sleep deprivation.
AB  - OBJECTIVE: The circadian secretory profiles of cortisol and growth hormone (hGH)
      in normal subjects are interrelated. Slight alterations in cortisol secretion are
      paralleled by similar ones of hGH secretion. Under physiological conditions an
      inhibitory effect of glucocorticoids on hGH secretion is more potent than a
      stimulatory one, while in normal young subjects the nychtohemeral cortisol and
      hGH levels are lower and higher, respectively, post 24 hours total sleep
      deprivation, compared to baseline values. The aim of the present work was to
      further assess the qualitative characteristics of the 24-hour secretory patterns
      of these two hormones before and after 24 hours total sleep deprivation, by
      studying their non-linear profiles using fractal analysis. METHODS: Cortisol and
      hGH were measured in 24-hour samples drawn from 10 healthy men (mean age SD: 24
      +/- 1 yr, mean BMI SD: 25 +/- 1 kg/m2) before and after 24 hours total sleep
      deprivation. Twenty-four hour blood sampling was performed serially every 30 min
      the day before and the day after total sleep deprivation. The 24-hour hormone
      profiles were analyzed by Fourier spectrum, in order to verify periodicities; the
      corresponding attractors were drawn and their respective fractal dimensions were
      calculated using the box counting method. RESULTS: Diurnal cortisol levels before
      sleep deprivation gave rise to a fractal attractor with a D0 fractal dimension of
      2.65 +/- 0.03, which decreased, post-sleep deprivation, to D0: 2.18 +/- 0.04.
      Growth hormone before sleep deprivation gave rise to a fractal attractor with a
      D0 dimension of 1.96 +/- 0.60, which increased to 2.24 +/- 0.60 post-sleep
      deprivation. These post-sleep deprivation changes of the fractal dimensions of
      cortisol and hGH, suggest that sleep deprivation leads to a more regular
      secretory profile of cortisol, while it tends to render hGH secretory profile
      less regular. Additionally, these changes of the fractal dimensions parallell the
      previously described quantitative overall changes of these hormones. CONCLUSIONS:
      The post-sleep deprivation decrease of cortisol fluctuation might reflect the
      mechanism by which sleep deprivation temporarily improves mood in melancholic
      depression, a condition associated with hyperactivity of the hypothalamic
      pituitary-adrenal axis.

PMID- 12207554
TI  - Strategies for improving quality of life in older patients with metastatic breast
      cancer.
AB  - Given both the increase in the mean age of the population of Western countries
      and the high incidence of breast cancer beyond the age of 65 years, it is evident
      that breast cancer in older women will be a very common problem for the medical
      oncologist. Metastatic breast cancer is still not amenable to a cure; therefore
      quality of life during therapy is an important issue, which until recently has
      been poorly investigated. Similarly, despite recent advances in breast cancer
      therapy, physicians have been reluctant to enrol older patients in clinical
      trials, and there is a lack of data regarding this population. This review
      focuses on quality-of-life issues during metastatic breast cancer treatment in
      geriatric patients, comparing the standard therapeutic options and newer
      approaches. Although first-line endocrine therapy with tamoxifen remains a
      standard treatment, the newer third-generation aromatase inhibitors provide
      similar or better efficacy with fewer adverse effects and a better quality of
      life. It has been a common belief that chemotherapy impairs quality of life, but
      recent studies in advanced breast cancer have shown that this therapy has a
      positive effect on quality of life, at least in responders. Consequently,
      chemotherapy should not be denied to elderly patients with metastatic breast
      cancer, provided a prior geriatric assessment is performed to evaluate the risk
      benefit ratio. New chemotherapy strategies, such as the taxanes and orally
      administered chemotherapy, represent a very attractive alternative for a better
      quality of life in elderly patients with metastatic breast cancer.

PMID- 12207556
TI  - Effect of body composition on indices of insulin sensitivity and beta-cell
      function in healthy men.
AB  - OBJECTIVE: Several indices have been published to quantify insulin sensitivity
      from fasting plasma glucose and fasting plasma insulin levels as well as from the
      data obtained by the oral glucose tolerance test (oGTT). Obesity represents the
      main risk factor associated with development of insulin resistance and Type 2
      diabetes mellitus. The aim of this study was to evaluate the influence of body
      composition on various indices of insulin sensitivity and secretion in subjects
      with normal glucose tolerance. METHODS: A total of 33 male subjects (aged 26-51
      years, BMI 19.7-30.9 kg/m2) underwent a standard oral glucose tolerance test
      (oGTT). Thereafter the cut-off value of BMI = 25 kg/m2 was set to divide the
      group into normal subjects and subjects with overweight. Indices of insulin
      sensitivity and secretion were calculated from plasma glucose and insulin
      concentrations using the formulas proposed by Matthews et al. (1985), Cederholm
      and Wibell (1990), Matsuda and DeFronzo (1999) and Stumvoll et al. (2000).
      RESULTS: All subjects had a normal glucose tolerance according to standard
      diagnostic criteria. No difference was found in the course of glycemia, while
      overweight subjects displayed an enhanced insulin response (P < 0.01). BMI
      correlated closely with all indices. The correlation coefficient was highest in
      ISI(Matsuda), followed by ISI(Cederholm) and ISI(Stumvoll). The indices of
      insulin sensitivity all significantly increased in the overweight group. The
      groups did not differ in the values of index SecrHOMA. CONCLUSIONS: The easiest
      way to predict the insulin sensitivity and to control the development of insulin
      resistance in a subject with yet normal glucose tolerance, but at high risk of
      development of overt Type 2 diabetes is to calculate an index from glucose and
      insulin concentrations during an oGTT. However, the assessment of appropriate cut
      off values is necessary for introducing the indices in clinical practice.

PMID- 12207557
TI  - Steroid hormones in human semen with particular respect to dehydroepiandrosterone
      and its immunomodulatory metabolites.
AB  - OBJECTIVE: In addition to many components, seminal fluid contains also hormonal
      steroids. So far, the studies were focused mostly to androgens, their precursors,
      estrogens and also cortisol, in most instances in relation to sperm
      abnormalities. Our group detected for the first time in the ejaculate 7
      hydroxylated metabolites of dehydroepiandrosterone, believed to function as
      immunomodulatory and immunoprotective agents. Occurrence of steroids in seminal
      fluid and their possible role is reviewed in the first part of the article.
      METHODS: In a group of 34 men (age 21-46 years) with various problems of
      fertility the presence of 7-hydroxydehydroepiandrosterone isomers and
      dehydroepiandrosterone in seminal fluid was found. The concentrations of steroids
      in seminal fluid and plasma were determined by recently developed
      radioimmunoassay. In brief, the ejaculate was extracted twice with diethyl ether
      and the water phase was separated by freezing in solid carbon dioxide and
      evaporating the solvent to dryness. The dry residue was dissolved in
      methanol:water:light petroleum ether (1.3:1.0:0.3 ml) and mixed. After separation
      the water-methanolic phase was evaporated, the dry residue was re-dissolved in
      phosphate buffer and aliquots were used for RIA. The results were corrected for
      losses by counting the residual radioactivity of [(3)H] testosterone added
      initially to the sample of seminal fluid. RESULTS: The concentrations of 7
      hydroxydehydroepiandrosterone varied from 1.08 to as much as 15.7 nmol/l, while
      those of dehydroepiandrosterone were about five times higher. The concentrations
      of both 7-hydroxydehydroepiandrosterone isomers were close to or even higher than
      recently reported levels of these substances in blood serum. CONCLUSION: The
      presence of steroids derived from dehydroepiandrosterone by 7-hydroxylation with
      recently reported immunomodulatory activity was for the first time demonstrated
      in seminal fluid of normal men.

PMID- 12207558
TI  - Structure and activation of EGF receptor: minireview.

PMID- 12207559
TI  - The role of neuroendocrine system in the pathogenesis of rheumatic diseases
      (minireview).
AB  - Interactions between the neuroendocrine and immune system play an important role
      in maintaining and restoring homeostasis. In susceptible individuals a
      dysfunction of the neuroendocrine system may be one of the risk factors involved
      in the pathogenesis of rheumatic diseases. Specific causes of altered
      neuroendocrine function are still not fully elucidated. Accumulation of
      genetical, environmental, behavioral and other risk factors during long
      preclinical period may result in chronic imbalances in homeostatic mechanisms
      maintained by neuroendocrine, microvascular and immune systems. Chronic
      inflammatory stress mediated by humoral and neural signals during active stages
      of the disease and autoantibodies against the structures of the neuroendocrine
      system may further participate in the neuroendocrine dysfunction. In a subset of
      patients with rheumatoid arthritis (RA), an assumed defect of the hypothalamic
      pituitary-adrenocortical axis may be implicated in the pathogenesis. Results of
      some studies support the concept of adrenal dysfunction in women with
      premenopausal onset of the RA. Significantly lower levels of
      dehydroepiandrosterone sulfate (DHEAS) plasma levels of women who subsequently
      developed RA indicate that neuroendocrine dysfunction may be present already in
      preclinical period and thus are not only secondary due to ongoing inflammatory
      process. These findings are sketching the new prospects of possible primary
      prevention of RA in the future. The role of some other hormones including
      prolactin, growth hormone, sex hormones and involvement of autonomic nervous
      system in relation with the rheumatic diseases is also reviewed in the paper.
      Further research concerning their role in the pathogenesis of other rheumatic
      diseases will possibly provide new prospects in optimizing their therapy.

PMID- 12207560
TI  - Characterization of iron-binding motifs in Candida albicans high-affinity iron
      permease CaFtr1p by site-directed mutagenesis.
AB  - A peptide motif Glu-Xaa-Xaa-Glu has been implicated in direct binding of ferric
      iron in several proteins involved in iron transport, sensing or storage. However,
      it is not known whether the motif alone is sufficient for iron binding and
      whether functional replacement of the conserved residues by other amino acids
      with similar properties is possible. We previously identified a Candida albicans
      iron permease, CaFtr1p, which contains five Glu-Xaa-Xaa-Glu motifs [Ramanan and
      Wang (2000) Science 288, 1062-1065]. In this study, we investigated the role of
      each of these motifs in iron uptake by site-directed mutagenesis. Substitution of
      Ala for any one of the two Glu residues in Glu-Gly-Leu-Glu(158-161) abolished
      iron-uptake activity, while the same substitution in any of the other four motifs
      had little effect, indicating that only the motif at position 158-161 is required
      for iron transport. We then evaluated the importance of each of the residues
      within and immediately adjacent to this motif in iron uptake. The permease
      remained active when any one of the Glu residues was replaced by Asp, while it
      became inactive when both were replaced. We also found that the amino acid
      immediately in front of Glu-Gly-Leu-Glu(158-161) must be either Arg or Lys. In
      addition, substitution of any of the two residues in the middle with several
      structurally distinct amino acids had no detectable effect on iron uptake. Here
      we propose to extend the iron-binding motif to Arg/Lys-Glu/Asp-Xaa-Xaa-Glu or
      Arg/Lys-Glu-Xaa-Xaa-Glu/Asp, which may serve as a guide for the identification of
      potential iron-binding sites in proteins.

PMID- 12207561
TI  - Phosphorylation is required for PMA- and cell-cycle-induced degradation of
      protein kinase Cdelta.
AB  - Classical and novel protein kinase C (PKC) isoforms are down-regulated as a
      result of chronic activation by certain tumour promoters and physiological
      stimuli; however, the mechanisms leading to down-regulation are not fully
      understood. In the present study, we have studied the PMA ('TPA')-induced
      degradation of PKCdelta in NIH 3T3 cells under culture conditions where PKCdelta
      displays cell-cycle-dependent down-regulation. In contrast with previous studies,
      a hyperphosphorylated form of this PKC isoform, promoted by calyculin A, was
      rapidly degraded in PMA-treated cells. Similarly, the presence of calyculin A
      enhanced the down-regulation of PKCdelta observed on G(1)/S-phase progression
      through the cell cycle. Analysis of phosphorylation-site mutants indicated that
      the T-loop Thr(505) phosphorylation site was critical for induced degradation.

PMID- 12207563
TI  - Effects of cytokines on contractile and dilator responses of airway smooth
      muscle.
AB  - 1. Increased bronchoconstrictor responses to contractile agonists and decreased
      dilator responses to beta-adrenoceptor agonists are characteristics of human
      asthma. One explanation for these features of asthma is that cytokines released
      in the asthmatic airway have direct effects on airway smooth muscle cells that
      alter their phenotype. 2. The present review summarizes data indicating that
      inflammatory cytokines, such as interleukin (IL)-1 beta and tumour necrosis
      factor-alpha, T helper (h) 1 cytokines, such as interferon-gamma, and Th2
      cytokines, such as IL-13 and IL-5, have the capacity to enhance contractile
      responses and/or decrease relaxant responses of airway smooth muscle. These
      effects are observed in smooth muscle from human airways and airway smooth muscle
      of other species. 3. Understanding the mechanistic basis for the effects of these
      cytokines may prove to be an important step in improving the efficacy of beta
      adrenoceptor agonists for the treatment of asthma.

PMID- 12207562
TI  - Topological analysis of peripherin/rds and abnormal glycosylation of the
      pathogenic Pro216-->Leu mutation.
AB  - Peripherin/ rds is an integral membrane glycoprotein found in the rim regions of
      vertebrate photoreceptor cell discs. The protein is believed to be involved in
      both formation and maintenance of the characteristic flattened morphology of the
      outer segment discs and its essential nature is demonstrated by the wide range of
      retinal degenerative disorders in which the protein has an involvement. Little
      structural data has been determined for peripherin/ rds, but a topological model
      of the protein has been proposed. In this paper, we present the first direct
      evidence for the topology of the protein through the use of scanning
      glycosylation mutagenesis. Both the topological data and the observation that
      only the Asn(229) site is efficiently glycosylated in this in vitro
      transcription/translation system support the common hypotheses. Additionally,
      expression of the Pro(216)-->Leu mutant demonstrates an abnormal glycosylation
      pattern, which may explain the mechanism by which this mutation precipitates a
      retinal degenerative phenotype.

PMID- 12207564
TI  - Neural control of the renal vasculature in angiotensin II-induced hypertension.
AB  - 1. Chronic administration of angiotensin (Ang) II causes an increase in blood
      pressure via a multitude of actions, including direct vasoconstriction,
      hypertrophy and increased sympathetic nerve activity. In the present study, we
      assessed whether the hypertension resulting from chronic Ang II alters the
      ability of the renal vasculature to respond to sympathetic activity. 2.
      Angiotensin II was administered for 7 weeks via an osmotic minipump at a dose of
      50 ng/kg per min, i.v., to a group of six rabbits. Blood pressure, measured at 0,
      1, 2 and 6 weeks after insertion of the pump, increased from 76 +/- 2 to 104 +/-
      6 mmHg at the end of 6 weeks, without any significant change in heart rate. The
      blood pressure in the control group remained constant at 76 +/- 2 mmHg. 3. After
      7 weeks, rabbits were anaesthetized and the renal nerves were stimulated at 0.5,
      1, 1.5, 2, 3, 5 or 8 Hz for 3 min at their supramaximal voltage (5.5 +/- 1.0 V in
      the normotensive group and 6.5 +/- 1.5 V in the hypertensive group) while the
      renal blood flow (RBF) response was recorded. Under anaesthesia, there was no
      difference in mean arterial pressure between the normotensive and hypertensive
      animals (77 +/- 2 and 80 +/- 7 mmHg, respectively). The resting RBF under these
      conditions was not significantly different in the hypertensive group (30 +/- 4 vs
      26 +/- 5 mL/min in the normotensive vs hypertensive group, respectively). 4.
      Stimulation at increasing frequencies was associated with increasing reductions
      in RBF (e.g. 36 +/- 8% at 2 Hz in normotensive rabbits and 48 +/- 7% at 2 Hz in
      hypertensive rabbits). However, there were no significant differences between RBF
      responses in normotensive and hypertensive rabbits. 5. We conclude that
      hypertension associated with chronic Ang II administration does not alter the
      response in RBF to electrical stimulation of the nerves.

PMID- 12207565
TI  - Effects of indomethacin on responses of regional kidney perfusion to vasoactive
      agents in rabbits.
AB  - 1. To determine whether differential release of products of arachidonic acid
      metabolism, via the cyclo-oxygenase pathway, underlies the diversity of responses
      of regional kidney perfusion to vasoactive agents, we tested the effects of
      intravenous indomethacin on responses to renal arterial bolus doses of vasoactive
      agents in pentobarbitone-anaesthetized rabbits. 2. Total renal blood flow (RBF)
      and regional kidney perfusion were determined by transit time ultrasound
      flowmetry and laser-Doppler flowmetry, respectively. 3. Responses of regional
      kidney blood flow to vasoactive agents were diverse: noradrenaline reduced
      cortical but not medullary perfusion, [Phe 2,Ile 3,Orn 8]-vasopressin reduced
      medullary perfusion more than cortical perfusion, endothelin-1 and angiotensin II
      increased medullary perfusion in the face of reduced cortical perfusion, while
      acetylcholine, bradykinin and the nitric oxide donor methylamine hexamethylene
      methylamine (MAHMA) NONOate all increased both cortical and medullary perfusion.
      4. Indomethacin administration was followed by reductions in total RBF (17 +/-
      6%), cortical perfusion (13 +/- 5%) and medullary perfusion (40 +/- 8%).
      Angiotensin II- and endothelin-1-induced increases in medullary perfusion were
      abolished by indomethacin, but indomethacin had no significant effects on
      responses of regional kidney perfusion to acetylcholine, bradykinin, MAHMA
      NONOate, noradrenaline and [Phe 2,Ile 3,Orn 8]-vasopressin. 5. Our results
      suggest that vasodilator cyclo-oxygenase products contribute to the maintenance
      of resting renal vascular tone, particularly in vascular elements controlling
      medullary perfusion. Cyclo-oxygenase products also appear to mediate endothelin-1
      and angiotensin II-induced increases in medullary perfusion. However, regionally
      specific engagement of cyclo-oxygenase-dependent arachidonic acid metabolism does
      not appear to contribute to the differential effects of noradrenaline and [Phe
      2,Ile 3,Orn 8]-vasopressin on cortical and medullary perfusion.

PMID- 12207566
TI  - Choleresis and inhibition of biliary lipid secretion induced by piperacillin in
      the rat.
AB  - 1. The effects of the administration piperacillin on bile flow and biliary lipid
      secretion were studied in male Wistar rats. 2. Intravenous injection of
      piperacillin at doses ranging from 0.3 to 3.0 mmol/kg bodyweight led to an
      increase in its biliary concentration and excretion rate. Maximal biliary
      excretion was reached at a dose of 2.0 mmol/kg piperacillin. 3. Excretion of the
      antibiotic into bile was associated with a marked choleresis. A linear
      relationship was observed between bile flow and piperacillin excretion, 5.7 micro
      L bile being produced per micro mol piperacillin excreted into the bile. 4.
      Continuous i.v. infusion of piperacillin at 2.0 mmol/100 g per min did not result
      in significant changes in bile acid or cholesterol secretion, but biliary
      phospholipid secretion was markedly reduced. The inhibitory effect on
      phospholipid secretion was also present when biliary lipid output had been
      previously increased by an infusion of taurocholate (200 nmol/100 g per min).
      Addition of taurocholate did not reverse the impairment of phospholipid secretion
      induced by piperacillin. 5. These results indicate that acute administration of
      piperacillin in the rat induces a marked choleresis by stimulating bile acid
      independent bile flow. The significant impairment in phospholipid secretion
      suggests a specific effect on intracellular supply and/or translocation across
      the canalicular membrane.

PMID- 12207567
TI  - Effects of creatine loading and depletion on rat skeletal muscle contraction.
AB  - 1. In humans, the effects of dietary creatine supplementation are controversial,
      with some studies showing increased muscle force and fatigue resistance and
      others reporting no effect on exercise performance. Little is known about the
      effects of creatine on muscle contractile properties. 2. Rats were fed a standard
      diet, creatine for 10 days or beta-guanidinopropionate, which depletes muscle
      creatine, for 7 days. Contractile properties were measured in isolated extensor
      digitorum longus and sternohyoid muscle as representative limb and upper airway
      dilator muscles, respectively. 3. Creatine had no effect on specific twitch and
      tetanic tension, contractile kinetics, twitch/tetanus tension ratio, the tension
      frequency relationship or fatigue in both muscles. beta-Guanidinopropionate had
      no effect on the twitch and tetanic tension, contractile kinetics, twitch/tetanus
      tension ratio or tension-frequency relationship, but significantly increased (P <
      0.05, anova) fatigue in both muscles. 4. Therefore, although creatine depletion
      increases fatigue, creatine loading has no effects on extensor digitorum longus
      and sternohyoid muscle contractile properties.

PMID- 12207568
TI  - Antiplatelet effects of policosanol (20 and 40 mg/day) in healthy volunteers and
      dyslipidaemic patients.
AB  - 1. The present study was undertaken to compare the effects of a higher dose of
      policosanol, a cholesterol-lowering drug, (40 mg/day) with the effects of 20
      mg/day policosanol on platelet aggregation in healthy volunteers and type II
      hypercholesterolaemic patients. 2. Study subjects were randomized to receive,
      under double-blind conditions, placebo or policosanol (20 or 40 mg/day) for 30
      days once a day. Blood sampling was performed at baseline and after 30 days on
      therapy. 3. Platelet aggregation was induced with three aggregating agents:
      arachidonic acid (AA), collagen and low doses of ADP. 4. Policosanol (20 and 40
      mg/day) moderately yet significantly reduced platelet aggregation, but no
      differences were observed in the effects produced by either dose of policosanol.
      In healthy volunteers, policosanol at 20 and 40 mg/day inhibited aggregation
      induced by 2 mmol/L AA (28.2 and 24.9%, respectively), 1 micro g/mL collagen
      (21.1 and 20.2%) and 1 micro mol/L ADP (30.9 and 29.1%). Changes that occurred
      following the administration of placebo were not significant, although an upward
      trend for collagen- and ADP-induced aggregation occurred in normal and
      hypercholesterolaemic subjects, respectively, thus partially masking the effects
      of policosanol on these responses. 5. The antiplatelet effects of policosanol at
      20 and 40 mg/day in hypercholesterolaemic patients were also similar, so that
      both doses inhibited aggregation induced by 1.5 mmol/L AA (20.1 and 33.0%,
      respectively), 0.5 micro g/mL collagen (22.7 and 21.1%) and 1 micro mol/L ADP
      (40.5 and 34.7%). 6. In addition, after 30 days of therapy, 20 and 40 mg/day
      policosanol significantly (P < 0.01) reduced low-density lipoprotein-cholesterol
      (15.9 and 17.0%, respectively) and total cholesterol (12.4 and 12.3%,
      respectively; P < 0.05), yet increased high-density lipoprotein-cholesterol
      values by 5% in both groups (P < 0.05). 7. Triglycerides were decreased compared
      with baseline, but not with respect to the placebo. 8. We conclude that the
      antiplatelet effects induced by 40 mg/day policosanol administered for 30 days to
      healthy volunteers and to hypercholesterolaemic patients were similar to the
      effects induced by 20 mg/day policosanol. Thus, no enhancement of the response
      was achieved with the use of a higher dose of policosanol in study patients.

PMID- 12207569
TI  - Withdrawal reveals lack of effect of prolonged antihypertensive treatment on
      intrinsic aortic wall stiffness in senescent spontaneously hypertensive rats.
AB  - 1. Chronic antihypertensive treatment lowers cardiovascular morbidity and
      mortality. The beneficial effect on the blood vessel wall may be due to the
      lowering of blood pressure (BP) and, hence, wall stress (WS), or to a treatment
      induced change in wall structure. 2. We have previously shown that, when
      evaluated at the same level of BP and WS, the stiffness of the aortic wall of old
      spontaneously hypertensive rats (SHR) is higher than that of young and adult SHR
      and that of age-matched Wistar-Kyoto (WKY) rats. In the present study, we tested
      the hypothesis that the intrinsic changes in wall composition and mechanics in
      old SHR can be modulated by long-term treatment with an angiotensin I-converting
      enzyme inhibitor (captopril; 40 mg/kg per day) combined with a diuretic
      (hydrochlorothiazide; 20 mg/kg per day) and that treatment withdrawal would
      reveal whether such changes are maintained when BP and WS return to pretreatment
      levels. 3. We evaluated aortic structure and mechanics in SHR following 1 week
      withdrawal of oral antihypertensive treatment from 3 to 15 months of age (n = 8).
      Results were compared with age-matched SHR that were maintained on treatment (n =
      12) or were not treated (n = 13) and with WKY rats (no treatment n = 11;
      maintained n = 11; withdrawn n = 10). 4. Isobaric aortic wall stiffness was
      estimated from the ratio of baseline aortic pulse wave velocity (PWV) to BP and
      the slope relating aortic PWV to BP following sodium nitroprusside-induced
      hypotension. Relative wall stiffening was estimated as the ratio of elastic
      modulus (EM) to WS. We argued that if treatment produced a change in wall elastin
      or collagen content, with a subsequent decrease in isobaric wall stiffness, then
      this would be maintained when BP increased following withdrawal of treatment. 5.
      In old SHR, treatment lowered isobaric wall stiffness (baseline PWV/BP 4.6 +/-
      0.3 cm/s per mmHg; slope relating PWV to BP 6.7 +/- 0.4 x 10-3 cm/s per mmHg and
      EM/WS 4.1 +/- 0.4 vs 6.1 +/- 0.4 cm/s per mmHg, 9.7 +/- 0.9 x 10-3 cm/s per mmHg
      and 8.9 +/- 1.1, respectively, without treatment; all P < 0.05). After 1 weeks
      treatment withdrawal, the indices (5.7 +/- 0.2 cm/s per mmHg, 9.1 +/- 0.2 x 10-3
      cm/s per mmHg and 7.2 +/- 0.6) increased in parallel with the increase in WS to
      levels similar to those observed in untreated SHR. There were no significant
      differences among the WKY rat groups. 6. Treatment increased the elastin and
      collagen contents of the aortic wall in both SHR (196 +/- 13 and 128 +/- 5 vs 111
      +/- 9 and 86 +/- 4 mg/g wet weight, respectively, in untreated; P < 0.05) and WKY
      rats (190 +/- 19 and 135 +/- 4 vs 115 +/- 7 and 114 +/- 5 mg/g wet weight,
      respectively, in untreated; P < 0.05). This increase remained following
      withdrawal (213 +/- 26 and 118 +/- 4 vs 161 +/- 14 and 127 +/- 4 mg/g wet weight
      in SHR and WKY rats, respectively). 7. In summary, 1 year of treatment with
      captopril plus hydrochlorothiazide increases wall elastin content and reduces WS
      and stiffness in old SHR. Following withdrawal, elastin content remains high, but
      wall stiffness parallels WS in a manner similar to that in untreated SHR.

PMID- 12207570
TI  - Dual nitric oxide mechanisms of cholestasis-induced bradycardia in the rat.
AB  - 1. Cholestatic liver disease is associated with nitric oxide (NO) overproduction
      and bradycardia. Nitric oxide has a dual effect on sinoatrial node and its
      effects depend on its concentration. Nitric oxide can increase heart rate by
      activating hyperpolarization-activated pacemaker current (If) but, at high
      concentrations, it can potentially decrease heart rate by inhibition of L-type
      calcium current. In the present study, the responsiveness of isolated atria to
      CsCl (an inhibitor of the If current) and acetylcholine (ACh; which decreases L
      type calcium current through a NO-dependent pathway) were evaluated in bile duct
      ligated and sham-operated control rats. 2. Bile duct ligation induced a
      significant decrease in the negative chronotropic effect of CsCl (0.2-5 mmol/L),
      but increased the responsiveness of isolated atria to ACh (10-8 to 10-3 mol/L).
      These effects were restored after incubation of the atria in the presence of the
      NO synthase inhibitor NG-nitro-l-arginine methyl ester (0.1 mmol/L). 3.
      Anaesthetized bile duct-ligated rats showed bradycardia and the plasma levels of
      NO2-/NO3- were significantly higher in bile duct-ligated rats compared with sham
      operated animals. 4. Different and opposite responses of atria of cholestatic
      rats to CsCl and ACh can be explained by NO overproduction in bile duct-ligated
      animals. A dual role of NO in the regulation of the sinoatrial node may be
      responsible for this opposite effect and may have a role in the pathophysiology
      of cholestasis-induced bradycardia.

PMID- 12207571
TI  - Intravascular granulocyte aggregates caused by the selectin-binding carbohydrate
      fucoidin in pig kidneys.
AB  - 1. Renal postischaemic reperfusion injury constitutes a significant problem after
      kidney transplantation. The polysaccharide fucoidin improves postischaemic
      function in lamb hearts, presumably by blocking selectin-mediated leucocyte
      adhesion. 2. In the present study, eight pairs of ischaemic pig kidneys were
      reperfused in an ex vivo model with autologous blood with or without fucoidin
      (100 mg/L). 3. Fucoidin resulted in a significant decrease in renal blood flow
      (45 +/- 5 vs 178 +/- 22 mL/min per 100 g; P < 0.001) and increased vascular
      resistance (3.80 +/- 0.07 vs 0.60 +/- 0.12 mmHg/mL per min per 100 g; P < 0.001).
      4. Histological examination revealed granulocyte emboli in afferent glomerular
      arteries in five of six fucoidin-treated kidneys and in one of six controls
      (Fisher's exact test; P < 0.001). 5. In vitro experiments with human granulocytes
      showed that large granulocyte aggregates were induced by fucoidin at
      concentrations similar to those used in reperfused kidneys, whereas slightly
      lower doses of fucoidin prevented l-selectin-dependent homotypic granulocyte
      adhesion. 6. The formation of embolizing granulocyte aggregates defines a narrow
      therapeutic range for fucoidin and calls into question its experimental use as an
      inhibitor of selectin-mediated leucocyte adhesion.

PMID- 12207572
TI  - Actions of specific adenosine receptor A1 and A2 agonists and antagonists in
      recovery of phrenic motor output following upper cervical spinal cord injury in
      adult rats.
AB  - 1. Previous studies from our laboratory have established that a latent
      respiratory motor pathway can be activated to restore function to a hemidiaphragm
      paralysed by upper cervical (C2) spinal cord hemisection during a reflex known as
      the 'crossed phrenic phenomenon'. In addition, theophylline, a general adenosine
      A1 and A2 receptor antagonist, can activate the latent pathway by acting
      centrally through antagonism at adenosine receptors. 2. The present study was
      designed to assess the relative contributions of adenosine A1 and A2 receptors in
      inducing functional recovery in our model of spinal cord injury. Specific
      adenosine A1 and A2 agonists and antagonists were used in an electrophysiological
      study. 3. Our results demonstrate that, in hemisected rats, systemic
      administration of the adenosine A1 receptor-specific antagonist 1,3-dipropyl-8
      cyclopentylxanthine (DPCPX) restores, in a dose-dependent manner, phrenic nerve
      respiratory related output that is lost following hemisection. Furthermore, DPCPX
      augments respiratory activity in non-injured animals. The A2 receptor agonist CGS
      21680 mediates its effects by predominantly acting on peripheral rather than
      central nervous system (CNS) receptors. CGS-21680 modulates respiratory related
      phrenic nerve activity in non-injured animals by enhancing tonic activity, but
      does not induce recovery of phrenic nerve activity in hemisected animals in the
      majority of cases. When CGS-21680 was administered prior to DPCPX in hemisected
      rats, the magnitude of recovery of respiratory function was significantly greater
      than that elicited by DPCPX alone. However, when the A2 receptor agonist was
      administered after DPCPX, the magnitude of recovery was virtually unchanged,
      whereas activity in the right phrenic nerve was significantly enhanced. The A1
      receptor agonist N6-cyclohexyladenosine depressed respiratory activity in non
      injured, as well as hemisected, rats. The A2 receptor antagonist 3,7-dimethyl-1
      propargylxanthine did not affect respiratory activity. 4. We conclude that while
      antagonism at central adenosine A1 receptors mediates functional restitution in
      hemisected animals, activation of A2 receptors located outside of the CNS
      subserves the A1 receptor-mediated respiratory recovery.

PMID- 12207573
TI  - Ageing blunts the effects of nitric oxide on myocardial O2 consumption.
AB  - 1. In the present study, we tested the hypothesis that the negative myocardial
      metabolic effects of nitric oxide (NO) were reduced in old hearts. 2. Studies
      were conducted in 17 young (approximately 6 months) and 18 old (> 36 months) New
      Zealand anaesthetized open-chest rabbits. Either vehicle or s-nitroso-N
      acetylpenicillamine (SNAP; 10-4 mol/L; a NO donor) was applied to the epicardial
      surface of the left ventricle. Coronary blood flow (microspheres) and artero
      venous (a-v) O2 difference (microspectrophotometry) were used to determine
      subepicardial (EPI) and subendocardial (ENDO) O2 consumption. Wall thickening was
      determined ultrasonically. Cyclic GMP and guanylyl cyclase activity were also
      determined. Myocardial a-v O2 difference, flow, O2 consumption and wall
      thickening were comparable in young and old hearts. 3. The EPI and ENDO O2
      consumption of SNAP-treated young hearts decreased significantly (> 25%) compared
      with vehicle (saline). However, SNAP had no significant effects on the O2
      consumption of old hearts. In addition, SNAP decreased the percentage wall
      thickening in young (from 18.0 +/- 1.7 to 13.4 +/- 1.6%), but not old (from 14.5
      +/- 0.9 to 11.4 +/- 1.6%), hearts. Basal cGMP levels in old hearts were greater
      (approximately 70%) than those in young hearts (15.7 +/- 2.0 vs 9.0 +/- 0.8
      pmol/g, EPI). s-Nitroso-N-acetylpenicillamine increased cGMP in EPI (13.7 +/- 1.8
      pmol/g) and ENDO of young, but not old (18.7 +/- 2.3 pmol/g, EPI), hearts.
      Similar results were also obtained using another NO donor, namely sodium
      nitroprusside (SNP; 10-4 mol/L). Guanylyl cyclase activity was elevated in old
      rabbit hearts with 0.5 mmol/L SNP (131 +/- 12 vs 80 +/- 12 pmol/min per mg
      protein for old and young rabbits, respectively). 4. Thus, while older hearts had
      similar O2 consumption and wall thickening compared with young hearts, they
      responded less well to NO and had significantly elevated basal levels of
      myocardial cGMP.

PMID- 12207574
TI  - Fluvastatin remodels resistance arteries in genetically hypertensive rats, even
      in the absence of any effect on blood pressure.
AB  - 1. The aims of the present study were, first, to determine whether, in the
      genetically hypertensive (GH) rat, fluvastatin would lower blood pressure and
      remodel mesenteric resistance arteries (MRA) and the basilar artery and, second,
      to see whether treatment with a combination of fluvastatin and the angiotensin
      receptor antagonist valsartan would have any extra beneficial effect on blood
      pressure and vascular remodelling. 2. Male GH rats had tail-cuff systolic blood
      pressure (SBP) monitored weekly from the age of 7 to 12 weeks. Groups (n = 12-14)
      were treated with fluvastatin (4 mg/kg per day), valsartan (5 mg/kg per day),
      both mixed in with chow, or a combination of fluvastatin 4 mg/kg per day +
      valsartan 5 mg/kg per day. Untreated GH and a group of normotensive Wistar (N)
      rats served as control groups. 3. At 12 weeks of age, intra-arterial (i.a.) blood
      pressure was measured by femoral cannulation and rats were then perfused (at the
      SBP of the animal) with Tyrode's solution containing heparin and papaverine
      followed by 2.5% glutaraldehyde in Tyrode's solution; MRA and basilar arteries
      were embedded in Technovit. Serial sections were cut and Giemsa stained and
      stereological methods used to obtain media width, lumen diameter, medial cross
      sectional area (CSA) and the ratio of media width to lumen diameter. Hearts were
      weighed to determine left ventricular (LV) mass. 4. Fluvastatin had no effect on
      blood pressure or LV mass, whereas valsartan given alone or with fluvastatin
      significantly reduced both parameters. 5. In MRA, fluvastatin reduced medial CSA,
      increased lumen size and, therefore, probably decreased vascular resistance. The
      media/lumen ratio was reduced to a level below that seen with the combination
      treatment and to below that of the N group. 6. In the basilar artery, fluvastatin
      and valsartan showed similar outward remodelling of the lumen and reduction in
      the media/lumen ratio. The combination treatment group showed, in addition, a
      reduction in medial CSA and an even lower ratio than the GH group on fluvastatin
      or valsartan alone or the N group. 7. Although fluvastatin has no effect on blood
      pressure, it does cause significant remodelling of MRA and the basilar artery.
      These beneficial structural changes in a peripheral resistance artery bed and in
      an artery involved in regulating resistance in the brain are worthy of further
      study.

PMID- 12207575
TI  - Regulation of K+ channels underlying the slow afterhyperpolarization in enteric
      afterhyperpolarization-generating myenteric neurons: role of calcium and
      phosphorylation.
AB  - 1. Myenteric afterhyperpolarization-generating myenteric (AH) neurons serve as
      intrinsic primary afferent neurons of the enteric nervous system and generate
      prolonged or slow afterhyperpolarizing potentials (slow AHP). The slow AHP is
      generated by an increase in a Ca2+-activated K+ conductance (gK-Ca) and is
      inhibited by enteric neurotransmitters leading to increased excitability. 2.
      Using cell-attached patch-clamp recordings from AH neurons, we have shown that K+
      channels with an intermediate unitary conductance (IK channels) open following
      action potential firing. 3. In excised patches from AH neurons, we have
      identified an IK-like channel that can be activated by submicromolar levels of
      cytoplasmic Ca2+ and is not voltage dependent. 4. Application of the catalytic
      subunit of cAMP-dependent protein kinase to the cytoplasmic surface of inside-out
      patches inhibits the opening of IK-like channels previously activated by Ca2+. 5.
      The IK-like channels are resistant to external tetraethylammonium (5 mmol/L) and
      apamin (0.3-1 micro mol/L), but are inhibited by clotrimazole (10 micro mol/L).
      6. Our present data support the idea that an increase in the open probability of
      IK-like channels in AH neurons following an increase in cytoplasmic [Ca2+] is
      responsible for the slow AHP and their opening is modulated by kinases.

PMID- 12207576
TI  - Thiol reagents and nitric oxide modulate the gating of BKCa channels from the
      guinea-pig taenia caeci.
AB  - 1. The site of the direct modulation of the gating of BKCa channels by the nitric
      oxide donor s-nitroso-l-cysteine (NOCys) was examined in excised membrane patches
      of the guinea-pig taenia caeci by the use of various thiol (sulphydryl)-specific
      reagents, including N-ethylmaleimide (NEM) and three charged
      methanethiosulphonate (MTS) reagents, namely positively charged 2-aminoethyl MTS
      hydrobromide (MTSEA) and [2-(trimethylammonium)ethyl] MTS bromide (MTSET) and
      negatively charged sodium (2-sulphonatoethyl) MTS (MTSES), which all specifically
      convert sulphydryls to a disulphide. 2. At 10 micro mol/L, NOCys transiently
      increased the probability of opening (N.Po) of the BKCa channels (at 0 mV) after
      a delay of 1-2 min. 3. Disulphide-reducing agents, such as dithiothreitol (10
      micro mol/L), increased N.Po in a manner that was reversed by the sulphide
      oxidizing agent thimerosal (10 micro mol/L). Both positively charged MTSET (2.5
      mmol/L) and negatively charged MTSES (2.5 mmol/L) rapidly increased N.Po.
      However, only the MTSES-evoked increase in N.Po remained after a prolonged
      washout period. 4. The specific alkylating agent of cysteine thiols NEM (1
      mmol/L) and the positively charged, but membrane permeable, MTSEA (2.5 mmol/L)
      decreased N.Po (at 0 mV). 5. Pre-exposure of excised membrane patches to NEM or
      MTSES prevented the excitatory actions of NOCys (10 micro mol/L). 6. We conclude
      that MTSES and NOCys must modify thiols on cysteine residues within basic regions
      of the channel protein that would electrostatically exclude MTSEA and MTSET. A
      consensus sequence of various mammalian alpha-subunits of the BKCa channel
      reveals two pairs of cysteine residues surrounded by basic amino acids that could
      be the site of action for NOCys and MTSES.

PMID- 12207577
TI  - Atopiform dermatitis: what's in a name?

PMID- 12207578
TI  - Recent advances in cutaneous angiogenesis.
AB  - An understanding of the molecular basis of angiogenesis is key to the
      appreciation of many of the advances made in the field of neovascularization over
      the past two decades. The sequence of events involved in angiogenesis includes:
      (i) increased vascular permeability and leakage; (ii) degradation of basement
      membrane; (iii) endothelial cell proliferation and migration through the
      surrounding extracellular matrix; and (iv) maturation and stabilization of the
      newly formed vessel bed. This review provides an update on the molecular basis of
      such pathways in the skin, with particular emphasis on the endothelial cell
      specific vascular endothelial growth factor and angiopoietins as modulators of
      angiogenesis that can be targeted in therapy of cutaneous disease.

PMID- 12207579
TI  - Atopiform dermatitis.
AB  - It is proposed to introduce the term 'atopiform dermatitis' to describe patients
      who have dermatitis with many of the characteristics of true atopic dermatitis,
      but who are not atopic. Atopy should be defined as the genetically determined and
      environmentally influenced syndrome in which the primary immunological
      abnormality is the production of allergen-specific IgE. It is suggested that by
      making a distinction between atopiform dermatitis and true atopic dermatitis,
      subsequent genetic, immunological and therapeutic studies will be improved.
      Furthermore, atopiform dermatitis would be a more appropriate diagnosis for the
      atopic dermatitis-like skin diseases that may occur in syndromes such as
      phenylketonuria, Schwachman's syndrome, Wiskott-Aldrich syndrome, Netherton's
      syndrome, Job's syndrome, selective IgA deficiency, agammaglobulinaemia and
      ataxia telangiectasia. In contrast to patients with true atopy, patients with
      atopiform dermatitis can logically be advised that allergen avoidance is not
      required, as they have no allergen-specific IgE.

PMID- 12207580
TI  - Atopiform dermatitis: do we need another confusing name for atopic dermatitis?

PMID- 12207581
TI  - Naevi in allogeneic bone marrow transplantation recipients: the effect of graft
      versus-host disease on naevi.
AB  - BACKGROUND: Non-melanoma skin carcinoma is more common in transplant recipients,
      probably because of immunosuppression. An increased risk of developing melanoma
      could be a late effect of transplantation. The number of naevi, which is a risk
      marker for melanoma, is increased in renal transplant recipients of all ages and
      may be related to immunosuppression. The risk of melanoma has been suspected to
      be particularly high after bone marrow transplantation. Cutaneous graft-versus
      host disease (GVHD) might be an interesting model for the study of interactions
      between naevi and the immune system. OBJECTIVE: To assess whether aBMT exposes an
      individual to a particularly high risk of melanoma, using naevi as a surrogate
      measure of the risk. To improve our knowledge of the effect of the immune system
      on naevi, using GVHD as a model. METHODS: We carried out an epidemiological case
      control study with two age-, sex- and hair colour-matched controls for each case.
      The results were analysed with analysis of variance, a general linear model
      analysis and multivariate analysis. RESULTS: The number of naevi was not
      significantly increased in aBMT patients, as compared with controls, although
      there was a significant excess on the palms and legs. In exploratory subgroup
      case-control comparisons and with the general linear model, patients who were
      conditioned with a combination of two alkylating drugs at high doses, and
      patients who had an aBMT before the age of 20 years tended to have a higher count
      of naevi (P = 0.002 and P = 0.06, respectively). Conversely, there was a trend in
      favour of a lower count of naevi in patients with diffuse skin lesions of chronic
      GVHD (P = 0.01). These data were corroborated by multivariate analysis, which
      showed that conditioning with high-dose chemotherapy, the absence of severe
      chronic cutaneous GVHD and a young age at transplantation were the main variables
      that independently predicted an excess of naevi. CONCLUSIONS: This study of aBMT
      patients confirms that chemotherapy stimulates naevus growth. It also suggests
      for the first time that diffuse lesions of chronic cutaneous GVHD are associated
      with a decreased number of naevi. Whether allo-immunity, chronic skin
      inflammation or the masking of naevi by pigmentation and fibrosis is responsible
      for the decreased number of naevi requires further investigation. With respect to
      the long-term risk of melanoma in aBMT recipients, our results support an
      increased risk particularly when aBMT is performed at a young age, and when
      conditioning is with high doses of alkylating drugs.

PMID- 12207582
TI  - Cytokine production in nickel-sensitized individuals analysed with enzyme-linked
      immunospot assay: possible implication for diagnosis.
AB  - BACKGROUND: Patients with suspected allergic contact dermatitis still have to
      undergo patch testing for a correct diagnosis. As this has several disadvantages
      there is a need for additional methods, preferentially those that can be
      performed in vitro. Objectives To investigate the possibility of diagnosing
      contact allergy to nickel (Ni2+) using the enzyme-linked immunospot (ELISpot)
      assay that allows the analysis of cytokines at a single-cell level in ex vivo
      activated peripheral blood mononuclear cells (PBMC). METHODS: Eleven female
      patients and nine age- and sex-matched healthy volunteers participated in the
      study. All patients had a history of nickel allergy and a positive patch test
      reaction to NiSO4, while the controls' test was negative. PBMC were cultured in
      the presence or absence of NiCl2. Cell proliferation was measured with
      [3H]thymidine incorporation, and the number of cytokine-producing cells analysed
      with the ELISpot assay. RESULTS: The proliferative response of PBMC to Ni2+,
      expressed as stimulation index, was significantly higher in the nickel-allergic
      patients than in the control group. Using the ELISpot assay, we found that PBMC
      from nickel-allergic individuals responded to Ni2+ with significantly greater
      production of interleukin (IL)-4, IL-5, IL-13 and interferon-gamma, but not IL
      12, compared with the healthy controls. The number of IL-4- and IL-5-producing
      cells correlated with the number of IL-13-producing cells in the nickel-allergic
      patients, but Ni2+-induced PBMC proliferation did not correlate with the number
      of cytokine-producing cells for any of the cytokines tested. CONCLUSIONS: Our
      results indicate that the ELISpot assay could be a tool in the discrimination
      between nickel-allergic and non-allergic individuals.

PMID- 12207583
TI  - Different phenotypes in recessive dystrophic epidermolysis bullosa patients
      sharing the same mutation in compound heterozygosity with two novel mutations in
      the type VII collagen gene.
AB  - BACKGROUND: Dystrophic epidermolysis bullosa (DEB) is a bullous skin disease
      caused by mutations in the type VII collagen gene (COL7A1). OBJECTIVE: To
      elucidate the mutations shown by two patients with DEB and understand the
      clinical phenotypes that they displayed. METHODS: We have characterized two
      patients, one affected by the severe recessive Hallopeau-Siemens variant of DEB
      (HS-RDEB) and the other by a milder recessive DEB form. RESULTS: In both patients
      we identified the R2063W missense mutation. The second mutation, in the HS-RDEB
      patient, was a novel 344insG, leading to a premature termination codon of
      translation (PTC) in exon 3, while, in the other patient, it was a novel 4965C-
      >T transition, which creates a new donor splice site in exon 53. The effect of
      this anomalous splice site leads to the maturation of a 17-nucleotides-deleted
      mRNA containing a PTC. In addition to this aberrant transcript, a certain amount
      of full-length mRNA is also generated from the mutated pre-mRNA through splicing
      at the canonical site. CONCLUSIONS: In these patients therefore the severity of
      the phenotype depends on the second mutation. In the patient with the 344insG
      mutation, leading to a PTC, type VII collagen (COLVII) molecules are exclusively
      composed of chains containing the R2063W substitution; as a consequence, all
      anchoring fibrils (AF) are abnormal and the phenotype is severe. In the other
      patient, the 4965C-->T splicing mutation allows the synthesis of a certain
      quantity of normal chains and the consequent assembly of partially functional
      COLVII molecules and AF, thus explaining the mild phenotype.

PMID- 12207584
TI  - The polymorphism of transforming growth factor-beta1 gene in Japanese patients
      with systemic sclerosis.
AB  - BACKGROUND: Transforming growth factor (TGF)-beta has been shown to be a potent
      stimulator of collagen production by fibroblasts, and could play a role in the
      pathogenesis of systemic sclerosis (SSc). OBJECTIVE: To study the possible
      involvement of TGF-beta1 gene polymorphism in Japanese patients with SSc.
      METHODS: Fifty-nine patients with SSc and 110 normal subjects were studied.
      Genomic DNA was extracted from skin tissues, and was amplified in a thermal
      cycler, generating a TGF-beta1 gene fragment with a size of 294 bp. The T to C
      transition at T869C (Leu10Pro) and the G to C transition at G915C (Arg25Pro) were
      identified by digestion with MspA1I and BglI, respectively. RESULTS: At T869C
      (Leu10Pro), the frequency of the C allele in SSc (65.3%) was significantly higher
      than in normal controls (50.5%) (P < 0.01). SSc showed C/C allele 42.4%, C/T
      45.8% and T/T 11.2%. Normal controls showed C/C allele 26.4%, C/T 48.2% and T/T
      25.5%. The frequency of the C/C allele in SSc was significantly higher than in
      normal controls, in comparison with the T/T allele (P < 0.02), but no significant
      difference was found between the frequency of the C/C allele vs. the C/T allele.
      The frequency of the C/C allele showed no significant difference between diffuse
      and limited SSc. At G915C (Arg25Pro), all the normal controls and SSc patients
      showed only the G/G allele. These results are different from a previous study in
      which the frequency of the T/T allele was high in SSc at T869C (Leu10Pro).
      CONCLUSIONS: This discrepancy may indicate that Japanese patients with SSc show a
      different genetic predisposition to TGF-beta1.

PMID- 12207586
TI  - Spectrum of subepidermal immunobullous disorders seen at the National Skin
      Centre, Singapore: a 2-year review.
AB  - BACKGROUND: The subepidermal immunobullous disorders (SEIBDs) comprise bullous
      pemphigoid (BP), cicatricial pemphigoid (CP), epidermolysis bullosa acquisita
      (EBA), linear IgA disease (LAD), dermatitis herpetiformis (DH), pemphigoid
      gestationis (PG) and bullous systemic lupus erythematosus (BSLE). They are
      thought to be rarer in the Far East than in western Europe. OBJECTIVE: This 2
      year retrospective study investigates the spectrum seen at our centre and the
      minimum estimated incidence of each. PATIENTS AND METHODS: A total of 67 patients
      seen at the National Skin Centre (NSC), Singapore between January 1998 and
      December 1999 were diagnosed as having an SEIBD. Fifty-nine (88%) had BP, four
      (6%) had EBA, two (3%) LAD and two (3%) BSLE. There were no cases of CP, DH or PG
      diagnosed during this period. The minimum estimated incidence in our local
      population was 7.6, 0.5, 0.26 and 0.26 per million population per year,
      respectively. The mean age of onset was 77, 68, 65 and 31 years, respectively.
      RESULTS: BP is the commonest SEIBD seen locally, with an incidence at least equal
      to that in western Europe. It is diagnosed at our centre three times more
      frequently than pemphigus. There is a predilection for ethnic Chinese but not
      Indian. EBA is twice as common as in western Europe and shows a predilection for
      ethnic Indians. LAD is rare here compared to China, despite the predominant
      Chinese population. BSLE is also rare. In contrast to western Europe, CP, DH and
      PG are very rare in Singapore. CONCLUSIONS: This is the first study from this
      region to show that certain SEIBDs are not rarer in the Far East, as previously
      thought.

PMID- 12207585
TI  - Molecular cytogenetic analysis of cutaneous T-cell lymphomas: identification of
      common genetic alterations in Sezary syndrome and mycosis fungoides.
AB  - BACKGROUND: Data on genome-wide surveys for chromosome aberrations in primary
      cutaneous T-cell lymphoma (CTCL) are limited. OBJECTIVE: To investigate genetic
      aberrations in CTCL. METHODS: We analysed 18 cases of Sezary syndrome (SS) and 16
      cases of mycosis fungoides (MF) by comparative genomic hybridization (CGH)
      analysis, and correlated findings with the results of additional conventional
      cytogenetics, fluorescent in situ hybridization (FISH) and allelotyping studies.
      RESULTS: CGH analysis showed chromosome imbalances (CIs) in 19 of 34 CTCL cases
      (56%). The mean +/- SD number of CIs per sample was 1.8 +/- 2.4, with losses (1.2
      +/- 2.0) slightly more frequent than gains (0.6 +/- 1.0). The most frequent
      losses involved chromosomes 1p (38%), 17p (21%), 10q/10 (15%) and 19 (15%), with
      minimal regions of deletion at 1p31p36 and 10q26. The commonly detected
      chromosomal gains involved 4/4q (18%), 18 (15%) and 17q/17 (12%). Both SS and
      late stages of MF showed a similar pattern of CIs, but no chromosomal changes
      were found in three patients with T1 stage MF. Of the 18 SS cases also analysed
      by cytogenetics, seven showed clonal chromosome abnormalities (39%). Five cases
      had structural aberrations affecting chromosomes 10 and 17, four demonstrated
      rearrangement of 1p and three revealed an abnormality of either 6q or 14q
      consistent with CGH findings. FISH analysis showed chromosome 1p and 17q
      rearrangements in five of 15 SS cases, and chromosome 10 abnormalities in four SS
      cases consistent with both the G-banded karyotype and the CGH results. In
      addition, allelotyping analysis of 33 MF patients using chromosome 1 markers
      suggested minimal regions of deletion at D1S228 (1p36), D1S2766 (1p22) and D1S397
      (1q25). CONCLUSIONS: These findings provide a comprehensive assessment of genetic
      abnormalities in CTCL and a rational approach for further studies.

PMID- 12207587
TI  - Dermoscopic diagnosis by a trained clinician vs. a clinician with minimal
      dermoscopy training vs. computer-aided diagnosis of 341 pigmented skin lesions: a
      comparative study.
AB  - BACKGROUND: In the last few years digital dermoscopy has been introduced as an
      additional tool to improve the clinical diagnosis of pigmented skin lesions.
      OBJECTIVE: To evaluate the validity of digital dermoscopy by comparing the
      diagnoses of a dermatologist experienced in dermoscopy (5 years of experience)
      with those of a clinician with minimal training in this field, and then comparing
      these results with those obtained using computer-aided diagnoses. METHODS: Three
      hundred and forty-one pigmented melanocytic and non-melanocytic skin lesions were
      included. All lesions were surgically excised and histopathologically examined.
      Digital dermoscopic images of all lesions were framed and analysed using software
      based on a trained artificial neural network. Cohen's kappa statistic was
      calculated to assess the validity with regard to the correct diagnoses of
      melanoma and non-melanoma. RESULTS: Sensitivity was high for the experienced
      dermatologist and the computer (92%) and lower for the inexperienced clinician
      (69%). Specificity of the diagnosis by the experienced dermatologist was higher
      (99%) than that of the inexperienced clinician (94%) and the computer assessment
      (74%). Notably, computer analysis gave a higher number of false positives (26%)
      compared with the experienced dermatologist (0.6%) and the inexperienced
      clinician (5.5%). CONCLUSIONS: Our results indicate that analysis either by a
      trained dermatologist or an artificial neural network-trained computer can
      improve the diagnostic accuracy of melanoma compared with that of an
      inexperienced clinician and that the computer diagnosis might represent a useful
      tool for the screening of melanoma, particularly at centres not experienced in
      dermoscopy.

PMID- 12207588
TI  - Incidence of allergic contact sensitization in Danish adults between 1990 and
      1998; the Copenhagen Allergy Study, Denmark.
AB  - BACKGROUND: Studies of incidence of contact allergy in a general population have
      not been reported. Data from incidence studies may support and direct strategies
      for prevention of contact allergy and allergic contact dermatitis. OBJECTIVE: To
      study the incidence of contact allergy and evaluate risk factors for developing
      contact allergy in an adult general population sample. PATIENTS AND METHODS: In
      1990 a random sample of 567 persons of the 15-69-year-old population living in
      the western part of Copenhagen County (Denmark) was patch tested in a cross
      sectional study. In 1998 a follow-up study was performed. Of 540 invited, 365
      (68%) were patch tested again. RESULTS: In the follow-up study, 37 persons (12%)
      of the 313 patch-test-negative persons in 1990 had developed one or more positive
      patch tests (incident contact allergy). Twenty cases (6%) of incident nickel
      allergy and 25 cases (8%) of incident contact allergy to one or more haptens
      other than nickel were found. The data indicate that female sex, young age and
      ear piercing (before 1990) were risk factors for developing nickel allergy.
      Between 1990 and 1998 metal contact dermatitis was reported in seven women with
      incident nickel allergy. Six of these women had bought the eliciting item in
      Denmark before 1995, when vigorous control of the Danish nickel legislation was
      introduced. CONCLUSIONS: We found a considerable number of incident cases of
      contact allergy in the adult population. The results of the study support the
      actions taken to restrict the use of the allergens most frequently encountered,
      and to increase the labelling demands to products intended for prolonged contact
      with the skin or a combined action.

PMID- 12207589
TI  - Evaluation of the role of contact sensitization and photosensitivity in the
      pathogenesis of poikiloderma of Civatte.
AB  - BACKGROUND: Poikiloderma of the face and neck (Civatte) is a rather common,
      indolent, chronic dermatosis, most often affecting menopausal females. Cumulative
      excessive sun exposure, a phototoxic or a photoallergic reaction, hormonal
      changes of menopause and genetic factors have all been incriminated in its
      obscure aetiopathogenesis. OBJECTIVE: To evaluate the role of contact
      sensitization and photosensitivity in the pathogenesis of poikiloderma of Civatte
      (PC). METHODS: Thirty-two patients (24 females and eight males, age range 38-74
      years) with PC were patch tested with the European standard series and the
      fragrance series, and were photopatch tested with the photoallergens series.
      Additionally, photo-testing with a monochromator was performed. RESULTS: Thirteen
      of 32 patients (40.62%) had one or more positive reactions to allergens of the
      standard series. Eight patients (25%) had positive reactions to fragrance mix
      and/or Balsam of Peru, which are included in the standard series, or to allergens
      of the fragrance series. Nickel sulphate was the single most common cause of
      contact sensitization (18.75%) among our patients. Ninety-seven subjects, who
      were patch tested with the standard series for suspected allergic contact
      dermatitis of the face and/or neck, served as age, sex and site controls. Of
      these, nine (9.27%) had one or more positive reactions to fragrance compounds.
      Statistical analysis showed a statistically significant difference in the
      frequency of positive reactions to fragrances between the PC group and the
      control group (chi2 value = 3.91, P < 0.05). In contrast, none of the PC patients
      had a positive photopatch test for the allergens included in the photoallergens
      series. The estimated minimal erythemal dose for the PC group was in all cases
      within normal limits for all wavelengths of ultraviolet (UV) radiation examined.
      CONCLUSIONS: Contact sensitization, mostly to perfume ingredients, may develop in
      PC, possibly playing a pathogenetic part, at least in a subset of patients.
      Despite negative results of photopatch testing, an allergic photo-contact
      reaction cannot be definitely excluded. PC seems not to be a photosensitivity
      disorder of the type of chronic actinic dermatitis. UV radiation-induced dermal
      connective tissue changes are the predominant histological feature of PC, leading
      to telangiectasia due to loss of vascular support. Reticular pigmentation may
      result from a delayed hypersensitivity reaction to perfume and/or cosmetic
      ingredients. Patch testing with the standard series and avoidance of documented
      allergens may be of value in patients with PC.

PMID- 12207590
TI  - Premature apoptosis of keratinocytes and the dysregulation of keratinization in
      porokeratosis.
AB  - BACKGROUND: Porokeratosis is a dyskeratotic disorder of the skin characterized by
      cornoid lamella with parakeratosis, hyperkeratosis and loss of granular layers.
      The pathogenesis of porokeratosis and the mechanism(s) of its abnormal
      keratinization are still unknown. OBJECTIVE: To elucidate the mechanism(s) of
      abnormal keratinization that leads to the formation of cornoid lamellae in
      porokeratosis. METHODS: Apoptosis of keratinocytes was assessed in the skin of
      seven patients by an in situ apoptosis assay based on the terminal
      deoxynucleotidyl transferase-mediated dUTP-biotin nick-end labelling (TUNEL)
      reaction. Patterns of loricrin and involucrin expression were examined by
      immunohistochemistry. RESULTS: TUNEL-positive keratinocytes were observed in the
      epidermis underlying the cornoid lamella in all cases examined. Furthermore,
      loricrin expression was interrupted there, in contrast to involucrin, which was
      expressed diffusely in the lesional epidermis. CONCLUSIONS: These results suggest
      that an abnormal early keratinocyte apoptosis accompanied by dysregulation of
      terminal differentiation of those cells may be involved in the pathogenesis of
      porokeratosis.

PMID- 12207591
TI  - The effect of topical corticosteroids on Ki67 and p53 expression in vulval lichen
      sclerosus.
AB  - BACKGROUND: Topical corticosteroids have become the treatment of choice for
      genital lichen sclerosus (LS) and are believed to be required for long-term
      relief of symptoms. OBJECTIVE: To compare vulval LS that had been treated with
      topical corticosteroids, vulval LS that had not received topical corticosteroids,
      and histologically normal vulval skin. METHODS: We used immunohistochemistry to
      look for Ki67 expression and abnormal p53 expression. RESULTS: We found a
      statistically significant difference for p53 overexpression, with increased
      levels seen when comparing corticosteroid-treated LS with normal genital skin (P
      = 0.011). Ki67 expression was also significantly higher in the corticosteroid
      treated group compared with normal genital skin (P = 0.001), and increased levels
      were also found in the treated group compared with untreated LS (P = 0.05).
      CONCLUSIONS: Our data suggest that topical corticosteroids have an effect on cell
      cycle proteins in genital skin and, in particular, genital skin with LS changes.

PMID- 12207592
TI  - Malignant skin cancers in the Finnish Twin Cohort: a population-based study, 1976
      97.
AB  - BACKGROUND: Both hereditary and environmental factors are implicated in the
      aetiology of cutaneous neoplasms. Studies of twins make it possible to estimate
      the contribution of inherited genes to the development of disease. OBJECTIVE: To
      assess the importance of hereditary and environmental factors (including physical
      environment and lifestyles) in malignant melanoma and malignant nonmelanoma of
      the skin. METHODS: The Finnish Twin Cohort, comprising 25 882 adult like-sexed
      twins with established zygosity, was linked with the Finnish Cancer Registry to
      identify malignant skin cancers in a prospective follow-up from 1976 to 1997.
      Standardized incidence ratios were computed based on national rates. RESULTS:
      Sixty twins were diagnosed with melanoma and 49 twins with nonmelanoma during the
      follow-up. The risks of these cancers did not differ from the risk in the
      population at large. There was only one pair where both twins had a malignant
      skin cancer (dizygotic male twins both with squamous cell carcinoma).
      CONCLUSIONS: The near-total lack of concordance for skin cancer in twin pairs
      suggests that environmental and not hereditary effects are most important in the
      causation of malignant skin cancers in a white population with low levels of sun
      exposure.

PMID- 12207593
TI  - A randomized controlled trial of nurse follow-up clinics: do they help patients
      and do they free up consultants' time?
AB  - BACKGROUND: Nurse follow-up clinics have become increasingly popular in recent
      years. Their impact on service delivery within dermatology may be useful in
      relation to chronic diseases, where education and treatment concordance are
      important factors in disease management. OBJECTIVE: To assess the impact of
      providing a nurse follow-up clinic in addition to the normal service provided by
      the dermatology outpatient department at Queen's Medical Centre, Nottingham, and
      to obtain pilot data with which to inform future study design. METHODS: Newly
      referred patients aged >/= 14 years and with a diagnosis of either eczema or
      psoriasis were identified. In a randomized, parallel-group study with a follow-up
      period of 6 weeks, participants were randomized either to normal care, or to
      receive an additional session with a dermatology nurse specialist immediately
      after their consultation with the dermatologist. The primary outcome measure was
      change in quality of life at 6 weeks, as assessed by the Dermatology Life Quality
      Index (DLQI). Secondary outcomes comprised a comparison of patient knowledge at 6
      weeks and the number of consultations (in secondary and primary care) that
      occurred during the 6-week follow-up period. RESULTS: Both groups improved by
      approximately 3 points on the DLQI scale after 6 weeks. The between-group
      difference was 0.27 (95% confidence interval - 2.3 to 2.8, P = 0.83). Patients
      who had seen the nurse were more likely to know how long they should apply
      treatment (P = 0.05). There was also a marked difference in patients'
      understanding of how to obtain a repeat prescription (P = 0.01) and from whom
      they could receive further support (P < 0.001). Following the addition of this
      service, 33% of follow-up appointments with a doctor were cancelled in the nurse
      intervention group. CONCLUSIONS: Dermatology nurses can add to a dermatology
      consultation and provide effective patient education and support in managing a
      skin condition. With this added service nurses could help to free up
      dermatologists' time, thus allowing them to see more new patients. Cost
      effectiveness studies are now needed.

PMID- 12207594
TI  - A randomized controlled evaluator-blinded trial of intravenous immunoglobulin in
      adults with severe atopic dermatitis.
AB  - BACKGROUND: There is a need for alternative therapy in severe adult atopic
      dermatitis (AD). Intravenous immunoglobulin (IVIG) treatment has been shown to be
      beneficial in a few open observations, but evidence of effectiveness is still
      lacking. OBJECTIVE: To investigate whether treatment with IVIG is effective in
      adults with severe AD. METHODS: In a randomized evaluator-blinded trial, 10
      patients with severe AD were randomized to immediate or delayed (by 1 month)
      treatment with IVIG 2 g kg-1. Patients received an 8-h infusion of 1 g kg-1 daily
      for two consecutive days. They were assessed clinically at days 15, 30, 60 and
      90. The primary efficacy criterion was measurement of the severity scoring of AD
      (SCORAD) index at day 30. RESULTS: The SCORAD values were not significantly
      different between the two groups at day 30. Similarly, global evaluation of
      disease severity by patients did not show any clinically significant change at
      day 30. In the cohort of 10 patients, the mean percentage decrease in SCORAD as
      compared with baseline was, respectively, 15%[95% confidence interval (CI) 6-24%]
      and 22% (95% CI 5-39%) at 30 and 60 days after IVIG infusion. CONCLUSIONS: IVIG
      treatment was not associated with clinically significant improvement of AD signs
      and symptoms in this randomized study. Although this study may have been too
      small to detect a beneficial effect in a small subset of patients, the results do
      not support the common use of IVIG in refractory AD.

PMID- 12207595
TI  - Topical adapalene gel 0.1% vs. isotretinoin gel 0.05% in the treatment of acne
      vulgaris: a randomized open-label clinical trial.
AB  - BACKGROUND: Topical application of isotretinoin and adapalene has proved
      effective in treating acne vulgaris. Both drugs demonstrate therapeutic
      advantages and less irritancy over tretinoin, the most widely used treatment for
      acne. They both act as retinoid agonists, but differ in their affinity profile
      for nuclear and cytosolic retinoic acid receptors. OBJECTIVE: To compare the
      efficacy and tolerability of adapalene gel 0.1% and isotretinoin gel 0.05% in the
      treatment of acne vulgaris of the face, in a randomized open-label clinical
      trial. METHODS: Eighty patients were enrolled and were instructed to apply
      adapalene gel 0.1% or isotretinoin gel 0.05% once daily over a 12-week treatment
      period. Efficacy determination included noninflammatory and inflammatory lesion
      counts by the investigator and global evaluation of improvement. Cutaneous
      tolerance was assessed by determining erythema, scaling and burning with
      pruritus. RESULTS: Adapalene and isotretinoin gels were highly effective in
      treating facial acne. Adapalene gel produced greater reductions in
      noninflammatory and inflammatory lesion counts than did isotretinoin gel, but
      differences between treatments were not statistically significant. Adapalene gel
      was significantly better tolerated than isotretinoin gel during the whole
      treatment period. CONCLUSIONS: The two gels studied demonstrated comparable
      efficacy. When adapalene and isotretinoin were compared, significantly lower skin
      irritation was noted with adapalene, indicating that adapalene may begin a new
      era of treatment with low-irritant retinoids.

PMID- 12207596
TI  - Intermittent dosing of fluticasone propionate cream for reducing the risk of
      relapse in atopic dermatitis patients.
AB  - BACKGROUND: One of the most troublesome features of atopic dermatitis (AD) is its
      chronic relapsing nature, and there is a lack of published evidence on the best
      treatment strategy for long-term management of the disease. OBJECTIVE: To compare
      an intermittent dosing regimen of fluticasone propionate (FP) cream 0.05% (twice
      per week) with its vehicle base in reducing the risk of relapse when added to
      regular daily emollient in adult and paediatric subjects with stabilized AD.
      METHODS: Subjects (aged 3 months to 65 years) with moderate or severe AD were
      enrolled into an open-label Stabilization Phase of up to 4 weeks on daily
      emollients plus FP twice daily. Those subjects who achieved 'treatment success'
      (Global Assessment Score </= 2, erythema, pruritus, and
      papulation/induration/oedema scores </= 1) entered the double-blind Maintenance
      Phase. They continued with regular emollients and were randomized at a 2 : 1
      ratio to either intermittent FP or vehicle, once daily 4 days per week for 4
      weeks followed by once daily 2 days per week for 16 weeks. Subjects who relapsed
      on intermittent FP were discontinued from the study. Those who did not relapse
      continued for an additional 24 weeks on intermittent dosing for safety
      monitoring. RESULTS: A total of 372 (247 paediatric, 125 adult) subjects were
      enrolled into the Stabilization Phase. Of these, 348 (231 children, 117 adults)
      were randomized into the Maintenance Phase. Analysis of the primary efficacy
      parameter showed that subjects receiving intermittent FP cream (twice per week),
      in addition to regular daily emollients in the Maintenance Phase, were 7.7 times
      less likely to have an AD relapse than subjects receiving intermittent vehicle
      cream/emollients [Mantel-Haenszel (MH) estimate of the odds ratio, 95% confidence
      interval (CI) 4.6, 12.8; P < 0.001]. Paediatric subjects were 8.1 times less
      likely to have an AD relapse (95% CI 4.3, 15.2; P < 0.001) and adult subjects
      were 7.0 times less likely to have an AD relapse (95% CI 3.0, 16.7; P < 0.001).
      For subjects receiving intermittent FP cream/emollient, the median time to
      relapse could not be estimated as the majority remained controlled at 20 weeks.
      For those receiving intermittent vehicle/emollient, the median time to relapse
      was 4.7 weeks. For paediatric and adult groups, this was 5.1 and 4.1 weeks,
      respectively. Median exposure to FP for all subjects was 337 days. There was only
      one study drug-related adverse event (acne) and there were no reports of skin
      thinning or atrophy associated with the use of FP cream in paediatric or adult
      subjects. CONCLUSIONS: In paediatric and adult subjects, once stabilized with
      regular FP treatment, the risk of relapse of AD can be significantly reduced by
      extended intermittent dosing with FP cream in addition to regular emollient
      therapy.

PMID- 12207597
TI  - Cost-effectiveness analysis of a psoriasis care instruction programme with
      dithranol compared with UVB phototherapy and inpatient dithranol treatment.
AB  - BACKGROUND: This study was part of a large national cost-effectiveness analysis,
      and was funded by the National Fund for Investigational Medicine of the Health
      Care Insurance Board. OBJECTIVE: To compare the costs of treatment of moderate to
      severe psoriasis by dithranol short contact therapy in a care instruction
      programme (short contact therapy) with ultraviolet B phototherapy (UVB) and
      inpatient dithranol treatment (inpatient treatment), and relate these costs to
      treatment effectiveness. METHODS: An open randomized controlled multicentre study
      was performed. The costs (both medical and non-medical) were calculated for the
      following periods: during treatment, per month during remission, after a relapse,
      and following an unsuccessful treatment. The effectiveness measures were the
      clinical response rate and the number of clearance days during follow-up.
      RESULTS: The data from 216 patients were analysed. The mean overall costs per
      patient during treatment were euro;1641, euro;1258 and euro;7706 for short
      contact treatment, UVB and inpatient treatment, respectively. During the
      clearance period the mean costs per month per patient were euro;19, euro;5 and
      euro;25, respectively. The clinical response rates were 57%, 57% and 85%,
      respectively. The mean number of clearance-days after short contact treatment was
      160 [median 119; interquartile range (0-357)], which was not significantly
      different from the other two strategies: 211 clearance-days after inpatient
      treatment [241 (99-350)] and 136 clearance-days after UVB [81 (0-266)].
      CONCLUSIONS: Short contact treatment is an attractive alternative for patients
      with moderate to severe psoriasis currently treated by inpatient treatment, as
      the costs of short contact treatment were significantly lower and the number of
      clearance days was comparable. Considering the higher costs, short contact
      treatment is not a first choice treatment when compared with UVB.

PMID- 12207598
TI  - A novel A97P amino acid substitution in alpha-galactosidase A leads to a
      classical Fabry disease with cardiac manifestations.
AB  - BACKGROUND: Fabry disease results from a genetic deficiency of alpha
      galactosidase A (GLA) activity. Phenotype-genotype correlations in this condition
      have not as yet been fully elucidated. OBJECTIVE: To report a case of a male
      patient with classical Fabry disease and his mother, a heterozygous female with
      Fabry disease, showing cardiac involvement, and to identify the underlying GLA
      gene mutation in this particular phenotype. PATIENTS/METHODS: Genomic DNA was
      extracted from the patient, his mother and the unaffected family members. Biopsy
      specimens of skin, heart and kidney were examined using light and electron
      microscopy. The mutation was identified by polymerase chain reaction and direct
      sequencing and was confirmed by restriction enzyme fragment length polymorphism.
      RESULTS: The G-->C transversion was identified in codon 97 of the GLA gene and
      resulted in an A97P amino acid substitution that was a novel pathogenic GLA gene
      mutation. The male patient who had classical Fabry disease was hemizygous and his
      mother was heterozygous for this mutation. CONCLUSIONS: These results indicate
      that the A97P amino acid substitution in GLA might tend to induce classical Fabry
      disease.

PMID- 12207599
TI  - Coexistence of beta2 microglobulin and lambda light chain in amyloid fibrils of
      dialysis-unrelated plasma cell dyscrasia-associated systemic amyloidosis.
AB  - BACKGROUND: Systemic amyloidosis occurs as a result of amyloid deposition in
      various tissues. The amyloid fibrils in systemic amyloidosis have been reported
      to originate from immunoglobulin light chains. OBJECTIVE: We studied the
      composition of amyloid fibrils from two patients with plasma cell-associated
      systemic amyloidosis (PASA). METHODS: A double immunofluorescence study of the
      lesional skin of PASA was undertaken. Amyloid proteins were extracted with
      distilled water from one case of PASA. RESULTS: The double immunofluorescence
      study showed that anti-lambda light chain and anti-beta2 microglobulin antibodies
      mostly reacted with the same area of amyloid deposit. Amyloid deposits from two
      patients with PASA who had never undergone haemodialysis showed a positive
      reaction with the antibodies for beta2 microglobulin as well as immunoglobulin
      lambda light chain. By the use of immunoblot assay of amyloid fibril proteins,
      polypeptides immunoreactive with antigamma light chain antibody (29 kDa) and with
      anti-beta2 microglobulin antibody (12 kDa) were detected. CONCLUSIONS: These
      results indicate that beta2 microglobulin is a component of amyloid fibrils in
      PASA.

PMID- 12207600
TI  - Psoriasis: response to high-dose intravenous immunoglobulin in three patients.
AB  - Treatment of recalcitrant psoriasis and psoriatic arthritis can be challenging,
      with treatment options limited by drug intolerance or poor efficacy. High-dose
      intravenous immunoglobulin (hdIVIg) has been used successfully in Kawasaki's
      disease and idiopathic thrombocytopenic purpura, where it has become the standard
      treatment. The literature also suggests its positive effect in the treatment of
      dermatological conditions, such as autoimmune chronic urticaria, atopic
      dermatitis, scleromyxoedema, dermatomyositis and autoimmune bullous disorders. We
      report three patients with treatment-resistant psoriasis and psoriatic arthritis
      who improved with hdIVIg.

PMID- 12207601
TI  - Drug-induced Sweet's syndrome in acne caused by different tetracyclines: case
      report and review of the literature.
AB  - Sweet's syndrome was first described in 1964. It is characterized by an acute
      onset of non-pruritic, painful reddish nodules on the head and neck, chest and/or
      the upper limbs, mostly accompanied by fever, general malaise and leucocytosis.
      Histopathological examination shows a diffuse dermal neutrophilic infiltrate. The
      pathogenesis is still not fully understood, and different diseases have been
      shown to be associated with this syndrome. However, although still very rare,
      there is an increase of reports on Sweet's syndrome induced by drugs. We describe
      a 30-year-old man who experienced acute neutrophilic dermatosis after systemic
      treatment with minocycline. Additionally, there is a strong possibility that the
      same patient developed a drug-induced Sweet's syndrome after oral administration
      of tetracycline and doxycycline.

PMID- 12207602
TI  - Multiple Epstein-Barr virus-associated subcutaneous angioleiomyomas in a patient
      with acquired immunodeficiency syndrome.
AB  - Tumours of smooth muscle origin, either solitary or multiple, are occasionally
      found in immunocompromised patients, particularly in children with acquired
      immunodeficiency syndrome (AIDS). Most of the reported AIDS-associated
      leiomyomatous neoplasms have been found in the visceral organs, and the tumour
      cells all possessed the Epstein-Barr virus (EBV) genome. Here we present a 32
      year-old-man with AIDS who developed three skin nodules on his lower left
      extremity. No other tumorous lesions were found using computed tomography scans.
      Two of the three nodules were resected for pathological examination.
      Histologically, both tumours were well circumscribed and located in the subcutis.
      The tumours were composed of interlacing fascicles of spindle-shaped cells with
      prominent vasculature and lymphocytic infiltration. No pleomorphism, mitosis or
      necrosis was seen. Immunohistochemically, the tumour cells were reactive to
      smooth muscle actin and desmin. Angioleiomyoma was diagnosed. EBV-encoded small
      RNAs were also demonstrated in the nucleus of the tumour cells by in situ
      hybridization but no EBV receptor (CD21) or latent membrane protein (LMP)-1 was
      found in the tumour cells. No human herpesvirus (HHV)-8 genome was detected in
      the lesion using polymerase chain reaction analysis. The results of this study
      indicated that EBV containing subcutaneous angioleiomyoma was another neoplasm
      that must be considered in patients with human immunodeficiency virus infection
      who develop skin nodules. The role of EBV in the pathogenesis of this unique
      neoplasm is still unknown.

PMID- 12207603
TI  - Dowling-Degos disease associated with squamous cell carcinomas on the dappled
      pigmentation.
AB  - We report the first case of Dowling-Degos disease associated with squamous cell
      carcinomas (SCCs) in the pigmented area of Dowling-Degos disease. A 64-year-old
      Japanese man manifested dappled pigmentation unusually localized to the buttocks,
      and two pigmented adenoid SCCs had developed on his left pigmented buttock. The
      other findings of Dowling-Degos disease were comedone-like lesions on the face
      and back, a finger-like fibroma in the right popliteal fossa, dystrophic
      fingernails, and a large number of seborrhoeic keratosis-like lesions
      predominantly on the flexural areas. Another unique clinical feature was the lack
      of vellus hair on the whole body surface. In addition to thin branching and
      elongation of rete ridges with basal hyperpigmentation, immature hair follicles
      surrounded by fibrosis and a lace-like pattern of the hair follicle epithelia
      were observed histologically. These epithelial hamartomatous features were
      consistent with Dowling-Degos disease. We speculate that the SCCs developed in
      relation to an underlying naevoid anomaly in pilosebaceous epithelia of Dowling
      Degos disease.

PMID- 12207604
TI  - Ferrochelatase gene polymorphism analysis for accurate genetic counselling in
      erythropoietic protoporphyria.
AB  - It has recently been shown that most cases of clinically overt erythropoietic
      protoporphyria (EPP) result from coinheritance of a mutated ferrochelatase gene
      and a commonly occurring low-expression normal variant allele. The identification
      of two polymorphic variant sequences associated with this low-expression allele
      now enables improved predictive counselling for couples where one partner has
      EPP. We describe a patient and his spouse in whom we have used such genetic
      analysis to provide an accurate estimate of the chance that their future
      offspring may suffer from EPP.

PMID- 12207605
TI  - New syndrome of hypotrichosis, striate palmoplantar keratoderma, acro-osteolysis
      and periodontitis not due to mutations in cathepsin C.
AB  - We report a mother and daughter with a syndrome of hypotrichosis, striate
      palmoplantar keratoderma, onychogryphosis, periodontitis, acro-osteolysis and
      psoriasis-like skin lesions. The syndrome resembles Papillon-Lefevre syndrome
      (PLS), characterized by palmoplantar keratoderma, periodontitis and psoriasis
      like skin lesions, and particularly Haim-Munk syndrome, an allelic variant of PLS
      with acro-osteolysis. Both are caused by mutations in the cathepsin C gene
      (CTSC). Our patients differ in the unique nature of the palmar keratoderma and
      hypotrichosis. We have sequenced CTSC in the mother without finding mutations in
      either coding or non-coding parts of the gene. We propose that our patients
      suffer from a new syndrome possibly caused by mutations in a gene that has a
      functional or structural relation with CTSC.

PMID- 12207606
TI  - A case of Sezary's syndrome associated with granulomatous lesions,
      myelodysplastic syndrome and transformation into CD30-positive large-cell
      pleomorphic lymphoma.
AB  - Sezary's syndrome (SS) is a leukaemic variant of mycosis fungoides, a cutaneous T
      cell lymphoma showing distinct clinical, histological, immunological, and
      genotypic features. We report a 10-year follow-up of a patient with SS exhibiting
      unusual features such as granulomatous skin lesions, transformation to a CD30
      positive large-cell pleomorphic T-cell lymphoma, and development of
      myelodysplastic syndrome and review the cases of SS reported in the literature
      with these unusual and rare complications.

PMID- 12207607
TI  - Hydroa vacciniforme-like primary cutaneous CD8-positive T-cell lymphoma.
AB  - An 8-year-old Taiwanese girl had a 6-month history of a relapsing papulovesicular
      eruption on her face that resembled hydroa vacciniforme (HV). Histologically,
      there was a dense infiltration of large atypical lymphocytic cells expressing
      CD8. TCR-gamma gene rearrangement study revealed a monoclonal band present in the
      DNA extracted from the specimen. A diagnosis of CD8+ cutaneous T-cell lymphoma
      (CTCL) was made. The patient was treated with Chinese herbal drugs and her skin
      lesions waxed and waned. At this writing, 11 months after establishment of the
      diagnosis, the skin lesions have been limited to the facial area and no definite
      evidence of systemic involvement is noted. To our knowledge, this is the first
      case of CD8+ primary CTCL with clinical features resembling HV.

PMID- 12207608
TI  - Childhood epidermolysis bullosa acquisita: a novel variant with reactivity to all
      three structural domains of type VII collagen.
AB  - Most patients with epidermolysis bullosa acquisita develop an autoimmune response
      to the non-collagenous (NC) 1 domain of type VII collagen. We report a 4-year-old
      girl of white European descent presenting with widespread blistering disease
      involving the face, hands, genital area and oral mucosa. Histopathology revealed
      subepidermal blisters, and linear deposits of IgG and C3 were seen along the
      dermal-epidermal junction on direct immunofluorescence (IF) microscopy of a
      perilesional skin biopsy. On indirect IF microscopy, circulating autoantibodies
      exclusively stained the dermal side of 1 mol L-1 NaCl-split skin. The patient's
      IgG autoantibodies labelled a 290-kDa protein on Western blotting of dermal
      extracts, and reacted with the NC1, NC2 and triple helical domains of type VII
      collagen on immunoblotting of recombinant and cell-derived fragments obtained by
      pepsin and collagenase digestion of the full-length protein. Oral
      methylprednisolone and dapsone led to clearance of lesions, which healed with
      mild scarring and milia formation. Treatment was discontinued after 1 year and
      the patient has now been in remission for more than 3 years.

PMID- 12207609
TI  - Follicular and epidermal alterations in patients treated with ZD1839 (Iressa), an
      inhibitor of the epidermal growth factor receptor.
AB  - We report the cutaneous side-effects of ZD1839 (Iressa), a new anticancer agent
      that acts by inhibiting epidermal growth factor (EGF) receptor signal
      transduction. Three patients receiving ZD1839 developed an eruption consisting of
      follicular papules and pustules in an acneiform distribution as well as diffuse
      fine scaling of the skin. Additionally, hair growth abnormalities were noted in
      two patients. Histologically, a superficial purulent folliculitis and disordered
      differentiation with focal parakeratosis were seen. The follicular eruption
      appeared to respond favourably to treatment with tretinoin cream and minocycline.
      The cutaneous adverse effects of ZD1839 are similar to those of other EGF
      receptor-targeted agents and result from direct interference with the functions
      of EGF receptor signalling in the skin.

PMID- 12207610
TI  - Myeloma-associated systemic amyloidosis presenting as digital nodules.

PMID- 12207611
TI  - Nail scabies as an initial lesion of ordinary scabies.

PMID- 12207612
TI  - Genetic syndrome with ichthyosis: congenital ichthyosis, follicular atrophoderma,
      hypotrichosis, and woolly hair; second report.

PMID- 12207613
TI  - Use of basiliximab as a cyclosporin-sparing agent in palmoplantar pustular
      psoriasis with myalgia as an adverse effect.

PMID- 12207614
TI  - A case of melanonychia caused by Fusarium solani.

PMID- 12207615
TI  - Myeloid markers should be undertaken in cases of CD56 positivity to exclude
      granulocytic sarcoma.

PMID- 12207616
TI  - Chronic recurrent multifocal osteomyelitis: a rare association with pyoderma
      gangrenosum in adults.

PMID- 12207617
TI  - Danger signals and skin sensitization.

PMID- 12207618
TI  - Injury to the skin induces p53- and Fas-dependent bystander keratinocyte
      apoptosis in vivo.

PMID- 12207619
TI  - Sartans, angiotensin II receptor antagonists, can induce psoriasis.

PMID- 12207620
TI  - Cutaneous lesions of Churg-Strauss syndrome associated with montelukast therapy.

PMID- 12207621
TI  - Scleroderma-like drug reaction to paclitaxel (Taxol).

PMID- 12207622
TI  - Topical imiquimod eradicates skin metastases of malignant melanoma but fails to
      prevent rapid lymphogenous metastatic spread.

PMID- 12207623
TI  - Localized toxic pustuloderma associated with nimesulide therapy confirmed by
      patch testing.

PMID- 12207624
TI  - Successful treatment of erosive vulvovaginal lichen planus with topical
      tacrolimus.

PMID- 12207625
TI  - Isolated thrombocytopenia associated with oral terbinafine.

PMID- 12207626
TI  - Basal cell carcinoma arising in professional radiodermatitis of the nail.

PMID- 12207627
TI  - Pharmacokinetics of tibolone in early and late postmenopausal women.
AB  - AIMS: Tibolone is a tissue-specific compound with favourable effects on bone,
      vagina, climacteric symptoms, mood and sexual well being in postmenopausal women,
      without stimulating the endometrium or breast. Since tibolone is used for the
      treatment of both young and elderly postmenopausal women, its pharmacokinetics
      were studied to investigate potential differences with age. In addition, the
      bioequivalence of the 1.25 and 2.5 mg tablets was evaluated. METHODS: Single
      doses of 1.25 or 2.5 mg of tibolone were given in a double-blind, randomized, two
      way cross-over study to women aged between 45 and 55 years or between 65 and 75
      years of age. RESULTS: Age did not have a significant effect on C(max), t(max),
      and t(1/2) of tibolone and its metabolites and on the body weight standardized
      oral clearance (CL/F kg(-1)) of the 3alpha- and 3beta-hydroxy tibolones. In early
      postmenopausal women, significantly lower values were found for the AUC(0,16 h),
      and AUC(0, infinity ) of 3alpha-hydroxy tibolone 24.6+/-6.6 vs 29.2+/-4.9 and
      27.1+/-6.9 vs 32.3+/-6.5 ng ml(-1) h for the 1.25 mg tablet, respectively, and
      45.4+/-13.9 vs 55.7+/-14.1 and 49.6+/-14.6 vs 62.6+/-17.3 ng ml-1 h for the 2.5
      mg tablet, respectively. When these values were adjusted for the significantly
      higher body weight of the early postmenopausal women, the differences
      disappeared. No significant differences between early and late postmenopausal
      women were found for the AUC(0,8 h), and AUC(0, infinity) of 3beta-hydroxy
      tibolone. The rate of absorption of tibolone and the rates of absorption or
      formation of the 3alpha- and 3beta-hydroxy tibolones were significantly higher
      after the 1.25 mg dose than after the 2.5 mg tablet, resulting in increases of
      32%, 27% and 17% for the dose normalized-C(max) of tibolone and the 3alpha- and
      3beta-hydroxy tibolones, respectively. tmax for tibolone and its metabolites was
      12-27% less after 1.25 mg compared to 2.5 mg, which was statistically
      significant. The two formulations were bioequivalent with respect to the dose
      normalized AUC(0, infinity) and the AUC(0,t(fix)) values for the 3alpha-hydroxy
      tibolone (ratio point estimate [90%, confidence limits]: 1.08 [1.04, 1.14] and
      1.08 [1.03, 1.13], respectively) and for the 3beta-hydroxy tibolone (1.07 [1.01,
      1.14] and 1.04 [0.96, 1.12], respectively). Both formulations were also
      bioequivalent with respect to CL/F kg(-1) and t(1/2). CONCLUSIONS: The
      pharmacokinetics of tibolone are similar in early (age 45-55 years) and late (65
      75 years) postmenopausal women. The 2.5 and 1.25 mg tablets are bioequivalent
      with respect to the extent of absorption. The rate of absorption or formation of
      the metabolites of tibolone were not bioequivalent, but these differences are
      considered to have no clinical relevance in view of the chronic administration of
      tibolone.

PMID- 12207628
TI  - Pharmacokinetics of the antianginal agent perhexiline: relationship between
      metabolic ratio and steady-state dose.
AB  - AIMS: 1) To develop an estimate of oral clearance (CL(Px)/F) for the antianginal
      agent perhexiline based on the ratio of cis-OH-perhexiline metabolite/parent
      perhexiline plasma concentrations at steady-state (C(OHPx,ss)/C(Px,ss)). 2) To
      determine whether the ratio measured in the first fortnight of treatment
      (C(i)(OHPx)/C(i)(Px)) may be used to guide patient dosing with perhexiline, a
      drug with a narrow therapeutic index, long half-life and saturable metabolism via
      CYP2D6. METHODS: Two retrospective studies were conducted reviewing patient
      records and data obtained from routine monitoring of plasma perhexiline and cis
      OH-perhexiline concentrations. RESULTS: Study 1 (n=70). At steady-state, the
      frequency distributions of CL(Px)/F and C(OHPx,ss)/C(Px,ss) were consistent with
      CYP2D6 metabolism. Putative poor metabolizers (approximately 8%) were identified
      by CL(Px)/F< or =50 ml min(-1) or C(OHPx,ss)/C(Px,ss)< or =0.3. A group of
      patients with CL(Px)/F> or =950 ml min(-1) may have been ultra-rapid
      metabolizers. In this group, the high CL(Px)/F values suggest extensive first
      pass metabolism and poor bioavailability. In patients with therapeutic plasma
      perhexiline concentrations (0.15-0.60 mg l(-1)), the variability in dose appeared
      directly proportional to CL(Px)/F (r2=0.741, P<0.0001). Study 2 (n=23). Using
      C(i)(OHPx)/C(i)(Px) patients were tentatively identified as poor, extensive and
      ultra-rapid metabolizers, with CL(Px)/F of 23-72, 134-868 and 947-1462 ml min(
      1), respectively, requiring doses of 10-25, 100-250 and 300-500 mg day(-1),
      respectively. CONCLUSIONS: The cis-OH-perhexiline/perhexiline concentration ratio
      may be useful for optimizing individual patient treatment with the antianginal
      agent perhexiline.

PMID- 12207629
TI  - Determination of the relative bioavailability of salbutamol to the lungs and
      systemic circulation following nebulization.
AB  - AIMS: Clinical studies comparing nebulized drug delivery systems could be flawed
      because of the high doses used. We have compared lung and total systemic delivery
      of salbutamol from a nebuliser with that from a metered dose inhaler by measuring
      urinary recovery of drug and its sulphate metabolite. METHODS: Twelve healthy
      volunteers provided urine samples at 0, 0.5, 1, 2, 4, 8, 12 and 24 h after the
      start of dosing. Formulations and doses were 5 x 100 microg oral solution (ORAL),
      5 x 100 microg from a metered dose inhaler (MDI), 2.5 mg using a nebuliser (NEB)
      and NEB with 25 g oral charcoal (NEBC). Each study phase was separated by 7 days
      and the order of dosing was randomized. RESULTS: Mean (s.d.) 30 min urinary
      salbutamol excretion after ORAL, MDI, NEB and NEBC was 0.4 (0.7), 12.1 (3.7),
      15.0 (3.9) and 18.2 (5.7) microg, respectively (all P<0.001 compared with ORAL).
      When normalized for the dose available for inhalation from MDI, NEB and NEBC, the
      mean (s.d.) 30 min urinary excretion of salbutamol was 2.4 (0.7), 2.9 (0.6) and
      2.7 (0.6)%, respectively, with a mean ratio (90% confidence interval) between NEB
      and NEBC, of 95.3 (91.1, 99.5)%. The mean (s.d.) excretion of salbutamol plus its
      metabolite over 24 h post ORAL, MDI, NEB and NEBC dosing was 297.9 (38.3), 290.3
      (41.4), 266.5 (44.6) and 151.7 (40.9) microg, respectively. The mean ratio (90%
      confidence interval) between MDI and ORAL, and NEB and ORAL were 97.5 (94.1,
      101.0) and 90.7 (81.2, 100.2)%, respectively. The NEBC data indicate that 6.07
      (1.04)% of the nominal nebulized dose was delivered to the lungs. CONCLUSIONS:
      The 30 min urinary recovery of salbutamol, an index of the relative systemic
      bioavailability of salbutamol following inhalation, can be used to compare the
      lung deposition of nebulized systems. Similarly, the urinary 24 h recovery of
      salbutamol plus its metabolite, an index of the relative systemic bioavailability
      of salbutamol following inhalation, can be used to compare the delivery of
      nebulized drug to the systemic circulation.

PMID- 12207630
TI  - Intestinal first pass metabolism of midazolam in liver cirrhosis --effect of
      grapefruit juice.
AB  - AIMS: Grapefruit juice inhibits CYP3A4 in the intestinal wall leading to a
      reduced intestinal first pass metabolism and thereby an increased oral
      bioavailability of certain drugs. For example, it has been shown that the oral
      bioavailability of midazolam, a CYP3A4 substrate, increased by 52% in healthy
      subjects after ingestion of grapefruit juice. However, this interaction has not
      been studied in patients with impaired liver function. Accordingly, the effect of
      grapefruit juice on the AUC of midazolam and the metabolite alpha
      hydroxymidazolam was studied in patients with cirrhosis of the liver. METHODS: An
      open randomized two-way crossover study was performed. Ten patients (3 females, 7
      males) with liver cirrhosis based on biopsy or clinical criteria participated.
      Six patients had a Child-Pugh score of A, one B and three C. Tap water (200 ml)
      or grapefruit juice were consumed 60 and 15 min before midazolam (15 mg) was
      administered orally. Plasma samples were analysed for midazolam and alpha
      hydroxymidazolam. RESULTS: Grapefruit juice increased the AUC of midazolam by
      106% (16, 197%) (mean (95% confidence interval)) and the AUC of the metabolite
      alpha-hydroxymidazolam decreased to 25% (12, 37%) (P<0.05 for both). The ratio of
      the AUCs of the metabolite alpha-hydroxymidazolam to midazolam decreased from
      0.77 (0.46, 1.07) to 0.11 (0.05, 0.19) (P<0.05). t(1/2) remained unaltered for
      both drug and metabolite. Midazolam C(max), t(max), and alpha-hydroxymidazolam
      t(max) increased, but these changes were not statistically significant, whereas
      C(max) of the metabolite decreased to 30% (14, 47%) (P<0.05). CONCLUSIONS: A
      marked interaction between oral midazolam and grapefruit juice was found and the
      data are consistent with a reduced first-pass metabolism of midazolam. This is
      likely to occur at the intestinal wall inhibition of CYP3A4 activity by
      grapefruit juice. These results indicate that patients with liver cirrhosis are
      more dependent on the intestine for metabolism of CYP3A4 substrates than subjects
      with normal liver function.

PMID- 12207631
TI  - Enantioselective distribution of albendazole metabolites in cerebrospinal fluid
      of patients with neurocysticercosis.
AB  - AIMS: Albendazole (ABZ) is effective in the treatment of neurocysticercosis. ABZ
      undergoes extensive metabolism to (+) and (-)-albendazole sulphoxide (ASOX),
      which are further metabolized to albendazole sulphone (ASON). We have
      investigated the distribution of (+)-ASOX (-)-ASOX, and ASON in cerebrospinal
      fluid (CSF) of patients with neurocysticercosis. METHODS: Twelve patients with a
      diagnosis of active brain parenchymal neurocysticercosis treated with albendazole
      for 8 days (15 mg kg(-1) day(-1)) were investigated. On day 8, serial blood
      samples were collected during the dose interval (0-12 h) and one CSF sample was
      taken from each patient by lumbar puncture at different time points up to 12 h
      after the last albendazole dose. Albendazole metabolites were determined in CSF
      and plasma samples by h.p.l.c. using a Chiralpak AD column and fluorescence
      detection. Population curves for CSF albendazole metabolite concentration vs time
      were constructed. RESULTS: The mean plasma/CSF ratios were 2.6 (95% CI: 1.9, 3.3)
      for (+)-ASOX and 2.7 (95% CI: 1.8, 3.7) for (-)-ASOX, with the two-tailed P value
      of 0.9873 being non-significant. These data indicate that the transport of ASOX
      through the blood-brain barrier is not enantioselective, but rather depends on
      passive diffusion. The present results suggest the accumulation of the (+)-ASOX
      metabolite in the CSF of patients with neurocysticercosis. The CSF AUC(+)/AUC(-)
      ratio was 3.4 for patients receiving albendazole every 12 h. The elimination half
      life of both ASOX enantiomers in CSF was 2.5 h. ASOX was the predominant
      metabolite in the CSF compared with ASON; the CSF AUC(ASOX)/AUC(ASON) ratio was
      approximately 20 and the elimination half-life of ASON in CSF was 2.6 h.
      CONCLUSIONS: We have demonstrated accumulation of the (+)-ASOX metabolite in CSF,
      which was about three times greater than the (-) antipode. ASOX concentrations
      were approximately 20 times higher than those observed for the ASON metabolite.

PMID- 12207633
TI  - An indirect response model of homocysteine suppression by betaine: optimising the
      dosage regimen of betaine in homocystinuria.
AB  - AIMS: To investigate the pharmacokinetics (PK) and pharmacodynamics (PD) of
      betaine in the treatment of classical homocystinuria due to cystathionine beta
      synthase (CbetaS) deficiency with a view to optimizing the dosage regimen.
      METHODS: Betaine was given as a single oral dose of 100 mg kg(-1) to six patients
      (age range 6-17 years) who normally received betaine but whose treatment had been
      suspended for 1 week prior to the study. Plasma betaine and total homocysteine
      concentrations were measured by high performance liquid chromatography (h.p.l.c.)
      at frequent intervals over 24 h. The best-fit PK model was determined using the
      PK-PD program Win-Nonlin and the concentration-time-effect data analysed by an
      indirect PD model. Using the PK and PD parameters, simulations were carried out
      with the aim of optimizing betaine dosage. RESULTS: Betaine PK was described by
      both mono- and bi-exponential disposition functions with first order absorption
      and a lag time. The correlation coefficient between betaine oral clearance and
      body weight was 0.6. Mean betaine clearance was higher in males than in females
      (P=0.03). PK-PD simulation indicated minimal benefit from exceeding a twice-daily
      dosing schedule and a 150 mg kg(-1) day(-1) dosage for betaine. CONCLUSIONS: PK
      PD modelling allows recommendations for optimal dosage of betaine in the
      treatment of homocystinuria, that have the potential for improved patient
      compliance and both therapeutic and pharmacoeconomic benefit.

PMID- 12207632
TI  - Relationships between body composition parameters and fluorouracil
      pharmacokinetics.
AB  - AIMS: To verify whether fluorouracil (FU) clearance (CL) and volume of
      distribution (V(ss)) are better correlated with specific body compartments, such
      as body cell mass (BCM), total body water (TBW) or fat free mass (FFM), rather
      than with body surface area (BSA) or total body weight (BW). METHODS: Thirty-four
      patients (13 females and 21 males) affected by colorectal cancer and receiving FU
      as adjuvant therapy entered the study. CL and Vss were determined after a 2 min
      i.v. injection of FU (425 mg m(-2)) and leucovorin (20 mg m(-2)). Body
      composition, in terms of BCM, TBW and FFM, was evaluated non-invasively by
      bioelectrical impedance analysis (BIA). RESULTS: Significant but poor
      correlations were found between CL or V(ss) and most anthropometric parameters,
      including BIA-derived measures (r2 range=0.10-0.21). However, when multiple
      regression analysis was performed with sex, TBW and FFM as independent variables,
      the correlations improved greatly. The best correlation was obtained between CL
      and sex (r2=0.44) and between V(ss) and sex (r2=0.36). FFM-normalized CL was
      significantly higher in women than in men (0.030+/-0.008 vs 0.022+/-0.005 l min(
      1) kg)(-1); 95% CI of difference 0.012, 0.003; P=0.003), suggesting that FU
      metabolism is more rapid in females. Surprisingly, V(ss) was highly correlated
      with CL (r2=0.67; CL=0.52+V(ss) x 0.040). This finding may either be explained by
      extensive drug metabolism in extra-hepatic organs or by variable inactivation on
      first-pass through the lung. Both these hypotheses need experimental validation.
      CONCLUSIONS: The pharmacokinetics of FU are better predicted by FFM and TBW than
      by standard anthropometric parameters and predictions are sex-dependent. The use
      of BIA may lead to improved dosing with FU.

PMID- 12207634
TI  - Pharmacokinetics and pharmacodynamics of low-dose methotrexate in the treatment
      of psoriasis.
AB  - AIMS: The aim of this 13 week, randomized, parallel-group study was to evaluate
      the relationship between the pharmacokinetics (PK) and pharmacodynamics (PD) of
      low-dose intermittent oral methotrexate (LDMTX) in patients with psoriasis.
      METHODS: Twenty-four psoriatic patients (15 male and 9 female, aged 31-73 years)
      were given weekly doses of MTX doses of either 7.5 mg or 15 mg with each dose
      divided into three aliquots given at 12 h intervals. The pharmacokinetics of MTX
      were evaluated at weeks 1 and 13. Skin impairment was assessed using the PASI
      scoring system (The Psoriasis Area and Severity Index) at baseline and at weeks
      5, 9 and 13 of therapy. Haematological and biochemistry tests were also performed
      at these times. RESULTS: The comparison of the areas under the plasma
      concentration-time curve (AUC(MTX)) after the first and third weekly doses showed
      that the extent of MTX accumulation in plasma was only about 12%. Two-way anova
      (factors: subject and the week of therapy) on the log-transformed AUC(MTX) showed
      no effect of the week of therapy (P>0.8). Moreover, the intraindividual
      variability in the AUC(MTX) was at least 4-fold less than the interindividual
      variability (F-test; P<0.01). The steady-state total plasma clearance of MTX
      ranged from 5.0 to 18.2 l h(-1) and was proportional to the renal clearance
      (r2=0.45, P<0.001) which accounted for 65+/-20% of the former. The renal
      clearance of 7-OHMTX was approximately 4-8% of that of the parent compound. PK/PD
      analysis revealed a highly significant inverse relationship between PASI
      (expressed as a percent of the initial value) and a steady-state AUC(MTX) (rs=
      0.65, P<0.001). Seventeen subjects (8 from the 7.5 mg group and 9 from the 15 mg
      group MTX, P=0.67) achieved a greater than 50% decrease in the initial PASI score
      and were classified as responders. Thirteen of 14 subjects with AUC(24,36 h)> or
      =700 nmol l(-1) h responded to pharmacotherapy. Conversely, only 4 out of 10
      subjects with AUC(24,36 h)<700 nmol l-1 h were responders (P<0.01, Fisher's exact
      test). CONCLUSIONS: A strong correlation was observed between the
      pharmacokinetics (AUC(MTX) at the steady state) and antipsoriatic effect (PASI
      score) of LDMTX. The considerable interindividual variability and low
      intraindividual variability in MTX pharmacokinetics support a role for
      therapeutic monitoring and dose individualization at the start of
      pharmacotherapy. The results of this study suggest that a steady state AUC(MTX)
      values of 700 nmol l(-1)h and higher are associated with a significantly better
      success rate of antipsoriatic therapy than lower values.

PMID- 12207635
TI  - The influence of CYP2B6, CYP2C9 and CYP2D6 genotypes on the formation of the
      potent antioestrogen Z-4-hydroxy-tamoxifen in human liver.
AB  - AIMS: To investigate in a large panel of 50 human liver samples the contribution
      of CYP2C9, CYP2D6, and CYP3A4 to the overall formation of the potent
      antioestrogen Z-4-hydroxy-tamoxifen, and how various genotypes affect its
      formation from tamoxifen. METHODS: The formation of Z-4-hydroxy-tamoxifen from 10
      microm tamoxifen was studied in human liver microsomes (n=50), characterized for
      CYP2B6, CYP2C9, CYP2D6 and CYP3A4 expression, and CYP2B6, CYP2C9 and CYP2D6
      genotype. The effect of chemical and monoclonal antibody inhibitors, and the
      formation in supersomes expressing recombinant CYP isoforms was also
      investigated. Z-4-hydroxy-tamoxifen was quantified using LC-MS analysis. RESULTS:
      Z-4-hydroxy-tamoxifen was formed by supersomes expressing CYP2B6, CYP2C9, CYP2C19
      and CYP2D6, but not CYP3A4. In agreement with these data, the mean formation of Z
      4-hydroxy-tamoxifen was inhibited 49% by sulphaphenazole (P=0.001), 38% by
      quinidine (P<0.05) and 13% by monoclonal antibody against CYP2B6 (MAB-2B6,
      P<0.05). Furthermore, Z-4-hydroxy-tamoxifen formation significantly correlated
      with both CYP2C9 expression (r(s)=0.256, P<0.05) and CYP2D6 expression
      (r(s)=0.309, P<0.05). Genotypes of CYP2D6, CYP2B6 and CYP2C9 had an effect on
      metabolite formation in such a way that samples with two nonfunctional CYP2D6, or
      two variant CYP2C9 or CYP2B6 alleles, showed lower enzyme activity compared with
      those with two functional or wild-type alleles, (5.0 vs 9.9 pmol mg(-1) protein
      min(-1), P=0.046, 5.1 vs 9.9 pmol mg(-1) protein min(-1), P=0.053, and 6.8 vs 9.4
      pmol mg(-1) protein min(-1), P=0.054, respectively). CYP2D6 and CYP2C9 contribute
      on average 45 and 46%, respectively, to the overall formation of Z-4-hydroxy
      tamoxifen. CONCLUSIONS: CYP2B6, CYP2C9 and CYP2D6 genotypes all affected Z-4
      hydroxy-tamoxifen formation and can predict individual ability to catalyse this
      reaction.

PMID- 12207636
TI  - Start of a selective serotonin reuptake inhibitor (SSRI) and increase of
      antiparkinsonian drug treatment in patients on levodopa.
AB  - AIMS: We determined whether the start of selective serotonin reuptake inhibitors
      (SSRI) in levodopa users was followed by a faster increase of antiparkinsonian
      drug treatment. METHODS: Selected were all levodopa users of 55 years and older
      from the PHARMO prescription database. The rate of increase of antiparkinsonian
      drug treatment was compared using Cox's proportional hazard model for starters of
      SSRI (n = 15) with starters of tricyclic antidepressants (TCA) (n = 31) and with
      patients not using antidepressants (n = 304), and was adjusted for age, gender,
      and duration of levodopa use. RESULTS: The hazard ratio for the SSRI group
      compared with the TCA group was 4.2 (95% confidence interval 1.4, 12.6) and
      compared with the second control group was 2.7 (1.2, 5.2). CONCLUSIONS: The start
      of SSRI therapy in levodopa users is followed by a faster increase of
      antiparkinsonian drug treatment.

PMID- 12207637
TI  - Non-antiarrhythmic drugs prolonging the QT interval: considerable use in seven
      countries.
AB  - AIMS: Many drugs belonging to different therapeutic classes appear to share a
      potentially fatal side-effect: ventricular tachyarrhythmias associated with QT
      prolongation. The aim of this study was to assess the relevance and the magnitude
      of the problem in seven countries by grouping all nonantiarrhythmic drugs
      according to the type of evidence on QT prolongation and analysing their sales
      data. METHODS: We divided all nonantiarrhythmic QT-prolonging agents into the
      following categories (in increasing order of clinical relevance): group A, drugs
      with published clinical or preclinical evidence on QT prolongation or with
      relevant official warnings; group B, drugs with published clinical or preclinical
      evidence; group C, drugs with published clinical evidence; group D, drug with
      published clinical evidence on torsades de pointes or ventricular arrhythmias
      associated with QT prolongation; group E, drugs belonging to group D with
      official warnings. We retrieved 1998 sales data from community pharmacies in
      seven countries (Australia, Denmark, England, Germany, Greece, Italy and Sweden).
      Data for individual agents were expressed as defined daily doses per 1000
      inhabitants per day (DDD/1000/day). Overall use in each country was calculated
      for each drug group. Groups D and E were considered as the most clinically
      relevant. RESULTS: Among the 102 nonantiarrhythmic agents meeting at least one of
      the inclusion criteria, 33 drugs had sales data > or =1 DDD/1000/day and 71 drugs
      had a use > or =0.1 DDD/1000/day in at least one country. Among the 37
      nonantiarrhythmic agents with published reports of ventricular arrhythmias
      associated with QT prolongation, 12 compounds had sales data > or =1
      DDD/1000/day. Total consumption in each country ranged: from 51.9 to 94.7
      DDD/1000/day for group A; from 51.6 to 92.7 DDD/1000/day for group B; from 37.1
      to 76.6 DDD/1000/day for group C; from 12.9 to 29.1 DDD/1000/day for group D; and
      from 5.8 to 15.3 DDD/1000/day for group E. CONCLUSIONS: In spite of wide
      variations in the sales of individual agents, the overall extent of use of
      nonantiarrhythmic QT-prolonging drugs was of the same order of magnitude in all
      countries. The significant use of drugs belonging to categories D and E should
      prompt careful risk/benefit assessment of each agent.

PMID- 12207638
TI  - Interaction between saquinavir soft-gel and rifabutin in patients infected with
      HIV.
AB  - AIMS: To evaluate the potential pharmacokinetic interaction between the HIV
      protease inhibitor saquinavir and rifabutin. METHODS: Fourteen HIV-infected
      patients provided full steady-state pharmacokinetic profiles following
      administration of rifabutin alone (300 mg once daily) or saquinavir soft-gel
      formulation (1200 mg three times daily) plus rifabutin (300 mg once daily) in
      this open label, partially randomized study. RESULTS: Coadministration of
      saquinavir and rifabutin resulted in a reduction in saquinavir AUC(0,8 h) and
      C(max)(0,8 h) of 47% (95% CI 30, 60%) and 39% (95% CI 11, 59%), respectively.
      Rifabutin AUC(0,24 h) and C(max)(0,24 h) was increased by an average of 44% (95%
      CI 17, 78%) and 45% (95% CI 14, 85%), respectively. Saquinavir in combination
      with rifabutin was well tolerated. Gastrointestinal intolerance and asymptomatic
      increases in liver enzymes were the only adverse events of note. CONCLUSIONS:
      Administration of rifabutin with saquinavir may decrease the efficacy of this HIV
      protease inhibitor.

PMID- 12207639
TI  - Intra-individual variability in urinary losartan oxidation ratio, an in vivo
      marker of CYP2C9 activity.

PMID- 12207643
TI  - Is intent-to-treat analysis always (ever) enough?

PMID- 12207642
TI  - The significance of QT interval in drug development.

PMID- 12207644
TI  - The odds of the three nons when an aptly prescribed medicine isn't working: non
      compliance, non-absorption, non-response.

PMID- 12207645
TI  - Pharmacogenetics and the future of medical practice.
AB  - Pharmacogenetic approaches are widely expected to bring about a "revolution" in
      medicine. While the application of molecular genetic approaches to disease
      research will provide us with new opportunities for progressively more targeted
      and, hopefully, more effective treatments, these developments will be
      evolutionary in nature and will, for their realization, still require the
      painstaking process that discovering and developing a new drug entails. It is
      also quintessential for the realization of these promises that we support a more
      rational understanding and more realistic expectations in the public at large
      through dialogue and information.

PMID- 12207646
TI  - Key amino acid residues required for aryl migration catalysed by the cytochrome
      P450 2-hydroxyisoflavanone synthase.
AB  - Isoflavonoids are distributed predominantly in leguminous plants, and play
      pivotal roles in the interaction of host plants with biological environments.
      Isoflavones in the diet also have beneficial effects on human health as
      phytoestrogens. The isoflavonoid skeleton is constructed by the CYP93C subfamily
      of cytochrome P450s in plant cells. The reaction consists of hydroxylation of the
      flavanone molecule at C-2 and an intramolecular 1,2-aryl migration from C-2 to C
      3 to yield 2-hydroxyisoflavanone. In this study, with the aid of alignment of
      amino acid sequences of CYP93 family P450s and a computer-generated putative
      stereo structure of the protein, candidates for key amino acid residues in
      CYP93C2 responsible for the unique aryl migration in 2-hydroxyisoflavanone
      synthase reaction were identified. Microsomes of recombinant yeast cells
      expressing mutant proteins of CYP93C2 were prepared, and their catalytic
      activities tested. The reaction with the mutant in which Ser 310 in the centre of
      the I-helix was converted to Thr yielded increased formation of 3
      hydroxyflavanone, a by-product of the 2-hydroxyisoflavanone synthase reaction, in
      addition to the major isoflavonoid product. More dramatically, the mutant in
      which Lys 375 in the end of beta-sheet 1-4 was replaced with Thr produced only 3
      hydroxyflavanone and did not yield the isoflavonoid any longer. The roles of
      these amino acid residues in the catalysis and evolution of isoflavonoid
      biosynthesis are discussed.

PMID- 12207647
TI  - Regulation of ADL6 activity by its associated molecular network.
AB  - Plant dynamin-like proteins consist of a group of high molecular weight GTPase
      with diverse structural arrangements and cellular localizations. In addition,
      unlike animal dynamins, there was no evidence for the involvement of any plant
      dynamin-like protein in clathrin-mediated vesicle trafficking. In this study we
      demonstrate that ADL6 (Arabidopsis dynamin-like protein 6), due to its domain
      arrangement, behaves similarly to the animal dynamins. The association of ADL6
      with clathrin-coated vesicles was demonstrated by co-fractionation and
      immunocytochemical studies. ADL6 also interacted via its C-terminus with gamma
      adaptin, an adaptor protein of clathrin-coated vesicles. Our results suggest that
      ADL6 participates in clathrin-mediated vesicle trafficking originating from the
      Golgi. In addition, our studies demonstrate that ADL6 intrinsic GTPase activity
      is regulated by its association with acidic phospholipids and an SH3 (Src
      homology 3)-containing protein.

PMID- 12207648
TI  - Knock-out of a putative transporter results in altered blue-light signalling in
      Chlamydomonas.
AB  - Nitrogen starvation and blue light are the two environmental cues that control
      sexual differentiation in Chlamydomonas reinhardtii. Insertional mutagenesis was
      applied to generate mutants that still require nitrogen starvation as the
      initiating signal for gametogenesis but were no longer dependent on irradiation.
      In one mutant analysed, sequences adjacent to the site of insertion were cloned
      and used for the isolation of a genomic clone that, upon transformation, could
      complement the mutant phenotype. The gene identified (LRG6) encodes two mRNAs
      that appear to be the products of differential splicing. The two putative gene
      products derived from these mRNAs differ in their C-terminal ends. Both predicted
      gene products exhibit multiple hydrophobic domains with alpha-helical secondary
      structure typical for integral membrane proteins. These proteins may form pores,
      and may function as transporters of as-yet unknown substrates. Since rendering
      the LRG6 gene non-functional resulted in light-independence of gamete formation,
      it is suggested that this transporter may inhibit signal flux from the
      photoreceptor to target genes - either directly by its activity or indirectly by
      serving as a scaffold for signalling proteins. Shutting off this transporter may
      be required for the activation of signal flux in this pathway. This concept is
      supported by the observed reduction in LRG6 mRNA levels during the first phase of
      gametic differentiation.

PMID- 12207649
TI  - The metal ion transporter IRT1 is necessary for iron homeostasis and efficient
      photosynthesis in Arabidopsis thaliana.
AB  - The mutants irt1-1 and irt1-2 of Arabidopsis thaliana were identified among a
      collection of T-DNA-tagged lines on the basis of a decrease in the effective
      quantum yield of photosystem II. The mutations responsible interfere with
      expression of IRT1, a nuclear gene that encodes the metal ion transporter IRT1.
      In irt1 mutants, photosensitivity and chlorophyll fluorescence parameters, as
      well as abundance and composition of the photosynthetic apparatus, are
      significantly altered. Additional effects of the mutation under greenhouse
      conditions, including chlorosis and a drastic reduction in growth rate and
      fertility, are compatible with a deficiency in iron transport. Propagation of
      irt1 plants on media supplemented with additional quantities of iron salts
      restores almost all aspects of wild-type behaviour. The irt2-1 mutant, which
      carries an En insertion in the highly homologous IRT2 gene of Arabidopsis
      thaliana, was identified by reverse genetics and shows no symptoms of iron
      deficiency. This, together with the finding that irt1-1 can be complemented by
      35S::IRT1 but not by 35S::IRT2, demonstrates that, although the products of the
      two genes are closely related, only AtIRT1 is required for iron homeostasis under
      physiological conditions.

PMID- 12207650
TI  - Post-transcriptional mechanisms control catalase synthesis during its light
      induced turnover in rye leaves through the availability of the hemin cofactor and
      reversible changes of the translation efficiency of mRNA.
AB  - The enzyme catalase is light-sensitive. In leaves, losses caused by
      photoinactivation are replaced by new enzyme and the rate of de novo synthesis
      must be rapidly and flexibly attuned to fluctuating light conditions. In mature
      rye leaves, post-transcriptional mechanisms were shown to control the rate of
      catalase synthesis. The amount of the leaf catalase (CAT-1) transcript did not
      increase with light intensity, but was even higher after dark exposure of light
      grown leaves. Initiation was apparently not limiting translation in the dark, as
      the association of the Cat1 mRNA with polysomes did not change notably under
      different light conditions. By analysing the translation of catalase polypeptides
      in cell-free systems with poly(A)+ RNA from leaves or with mRNA transcribed from
      a Cat1-containing cDNA clone, two mechanisms of post-transcriptional control were
      identified. First, translation of catalase depended on the presence of hemin. In
      leaves, the availability of hemin may signal the extent of catalase degradation
      as the hemin of the inactivated enzyme is recycled. Second, the translation
      efficiency of the Cat1 transcripts was reversibly modulated in a dose-dependent
      manner by the light intensity to which leaves were exposed, prior to extraction.
      The Cat1 mRNA from light-exposed leaves was translated much more efficiently than
      mRNA from dark-exposed leaves. The increase of its translation activity in vivo
      was not blocked by cordycepin but was suppressed by methylation inhibitors,
      indicating a reversible modification of pre-existing mRNA by methylation.
      Translation of in vitro synthesized Cat1 mRNA required a methylated cap
      (m7GpppG), but was virtually below detection when it contained an unmethylated
      cap (GpppG).

PMID- 12207651
TI  - Genotype-dependent transcriptional activation of novel repetitive elements during
      cold acclimation of alfalfa (Medicago sativa).
AB  - In a search for cold-regulated genes that are differentially expressed in alfalfa
      genotypes of contrasting freezing tolerance, we screened 1036 arrayed cDNA
      clones. The screening resulted in isolation of cDNA clones, which demonstrated
      dramatic differences in expression between hardy and un-hardy alfalfa varieties.
      Detailed analysis revealed that these cDNAs represent parts of novel non-coding
      repetitive elements carrying long-terminal repeats (LTR) and other retroelement
      like features. Despite strong expression under low temperatures, DNA templates
      remained highly methylated, and a drug-induced decrease in methylation did not
      activate transcription under normal temperatures. We identified that these
      repetitive elements represent a large family and could insert into, or be
      adjacent to, the unrelated polyprotein sequences of putative retrotransposons.
      These retrotransposons also showed low temperature-induced transcriptional
      activation; however, this activation was not genotype-dependent. The
      retroelements described in this study are the first retroelement characterized in
      the Medicago genus. Furthermore, they represent the only known example of
      genotype-specific cold-induced transcriptional activation of multiple copies of a
      repetitive element whose expression is associated with a genotype difference in
      cold acclimation.

PMID- 12207652
TI  - Opposite changes in membrane fluidity mimic cold and heat stress activation of
      distinct plant MAP kinase pathways.
AB  - Mitogen-activated protein kinases (MAPKs) appear to be ubiquitously involved in
      signal transduction during eukaryotic responses to extracellular stimuli. In
      plants, no heat shock-activated MAPK has so far been reported. Also, whereas cold
      activates specific plant MAPKs such as alfalfa SAMK, mechanisms of such
      activation are unknown. Here, we report a heat shock-activated MAPK (HAMK)
      immunologically related to ERK (Extracellular signal-Regulated Kinase)
      superfamily of protein kinases. Molecular mechanisms of heat-activation of HAMK
      and cold-activation of SAMK were investigated. We show that cold-activation of
      SAMK requires membrane rigidification, whereas heat-activation of HAMK occurs
      through membrane fluidization. The temperature stress- and membrane structure
      dependent activation of both SAMK and HAMK is mimicked at 25 degrees C by
      destabilizers of microfilaments and microtubules, latrunculin B and oryzalin,
      respectively; but is blocked by jasplakinolide, a stabilizer of actin
      microfilaments. Activation of SAMK or HAMK by temperature, chemically modulated
      membrane fluidity, or by cytoskeleton destabilizers is inhibited by blocking the
      influx of extracellular calcium. Activation of SAMK or HAMK is also prevented by
      an antagonist of calcium-dependent protein kinases (CDPKs). In summary, our data
      indicate that cold and heat are sensed by structural changes in the plasma
      membrane that translates the signal via cytoskeleton, Ca2+ fluxes and CDPKs into
      the activation of distinct MAPK cascades.

PMID- 12207653
TI  - Germination and storage reserve mobilization are regulated independently in
      Arabidopsis.
AB  - The phytohormone abscisic acid (ABA) inhibits the germination of many seeds,
      including Arabidopsis, but the mechanism for this is not known. In cereals, ABA
      inhibits the expression of genes involved in storage reserve mobilization. We
      have found that in Arabidopsis ABA decreases transcription from the promoters of
      marker genes for beta-oxidation and the glyoxylate cycle, essential pathways for
      the conversion of storage lipid (triacylglycerol) into sucrose. Thirty per cent
      of stored lipid is broken down over 6 days following imbibition of ABA-treated
      seed. Sucrose levels in ABA-treated seeds, rather than decreasing as under normal
      growth conditions, actually double during the 3 days following imbibition. This
      sucrose is derived from triacylglycerol as demonstrated by two mutants disrupted
      in the conversion of triacylglycerol into sucrose, kat2 and icl1, which do not
      accumulate sucrose in the presence of ABA. We conclude that the ABA block on
      germination is not a consequence of inhibition of storage lipid mobilization. Two
      independent programmes appear to operate, one that is blocked by ABA, governing
      developmental growth resulting in germination; and a second that governs storage
      lipid mobilization which is largely ABA-independent.

PMID- 12207654
TI  - Proof of C4 photosynthesis without Kranz anatomy in Bienertia cycloptera
      (Chenopodiaceae).
AB  - Kranz anatomy, with its separation of elements of the C4 pathway between two
      cells, has been an accepted criterion for function of C4 photosynthesis in
      terrestrial plants. However, Bienertia cycloptera (Chenopodiaceae), which grows
      in salty depressions of Central Asian semi-deserts, has unusual chlorenchyma,
      lacks Kranz anatomy, but has photosynthetic features of C4 plants. Its
      photosynthetic response to varying CO2 and O2 is typical of C4 plants having
      Kranz anatomy. Lack of night-time CO2 fixation indicates it is not acquiring
      carbon by Crassulacean acid metabolism. This species exhibits an independent,
      novel solution to function of the C4 mechanism through spatial compartmentation
      of dimorphic chloroplasts, other organelles and photosynthetic enzymes in
      distinct positions within a single chlorenchyma cell. The chlorenchyma cells have
      a large, spherical central cytoplasmic compartment interconnected by cytoplasmic
      channels through the vacuole to the peripheral cytoplasm. This compartment is
      filled with mitochondria and granal chloroplasts, while the peripheral cytoplasm
      apparently lacks mitochondria and has grana-deficient chloroplasts.
      Immunolocalization studies show enzymes compartmentalized selectively in the CC
      compartment, including Rubisco in chloroplasts, and NAD-malic enzyme and glycine
      decarboxylase in mitochondria, whereas pyruvate, Pi dikinase of the C4 cycle is
      localized selectively in peripheral chloroplasts. Phosphoenolpyruvate
      carboxylase, a cytosolic C4 cycle enzyme, is enriched in the peripheral
      cytoplasm. Our results show Bienertia utilizes strict compartmentation of
      organelles and enzymes within a single cell to effectively mimic the spatial
      separation of Kranz anatomy, allowing it to function as a C4 plant having
      suppressed photorespiration; this raises interesting questions about evolution of
      C4 mechanisms.

PMID- 12207656
TI  - Nitrogen-assimilating enzymes in land plants and algae: phylogenic and
      physiological perspectives.
AB  - An important biochemical feature of autotrophs, land plants and algae, is their
      incorporation of inorganic nitrogen, nitrate and ammonium, into the carbon
      skeleton. Nitrate and ammonium are converted into glutamine and glutamate to
      produce organic nitrogen compounds, for example proteins and nucleic acids.
      Ammonium is not only a preferred nitrogen source but also a key metabolite,
      situated at the junction between carbon metabolism and nitrogen assimilation,
      because nitrogen compounds can choose an alternative pathway according to the
      stages of their growth and environmental conditions. The enzymes involved in the
      reactions are nitrate reductase (EC 1.6.6.1-2), nitrite reductase (EC 1.7.7.1),
      glutamine synthetase (EC 6.3.1.2), glutamate synthase (EC 1.4.1.13-14, 1.4.7.1),
      glutamate dehydrogenase (EC 1.4.1.2-4), aspartate aminotransferase (EC 2.6.1.1),
      asparagine synthase (EC 6.3.5.4), and phosphoenolpyruvate carboxylase (EC
      4.1.1.31). Many of these enzymes exist in multiple forms in different subcellular
      compartments within different organs and tissues, and play sometimes overlapping
      and sometimes distinctive roles. Here, we summarize the biochemical
      characteristics and the physiological roles of these enzymes. We also analyse the
      molecular evolution of glutamine synthetase, glutamate synthase and glutamate
      dehydrogenase, and discuss the evolutionary relationships of these three enzymes.

PMID- 12207655
TI  - The VERNALIZATION INDEPENDENCE 4 gene encodes a novel regulator of FLOWERING
      LOCUS C.
AB  - The late-flowering, vernalization-responsive habit of many Arabidopsis ecotypes
      is mediated predominantly through repression of the floral programme by the
      FLOWERING LOCUS C (FLC) gene. To better understand this repressive mechanism, we
      have taken a genetic approach to identify novel genes that positively regulate
      FLC expression. We identified recessive mutations in a gene designated
      VERNALIZATION INDEPENDENCE 4 (VIP4), that confer early flowering and loss of FLC
      expression in the absence of cold. We cloned the VIP4 gene and found that it
      encodes a highly hydrophilic protein with similarity to proteins from yeasts,
      Drosophila, and Caenorhabditis elegans. Consistent with a proposed role as a
      direct activator of FLC, VIP4 is expressed throughout the plant in a pattern
      similar to that of FLC. However, unlike FLC, VIP4 RNA expression is not down
      regulated in vernalized plants, suggesting that VIP4 is probably not sufficient
      to activate FLC, and that VIP4 is probably not directly involved in a
      vernalization mechanism. Epistasis analysis suggests that VIP4 could act in a
      separate pathway from previously identified FLC regulators, including FRIGIDA and
      the autonomous flowering promotion pathway gene LUMINIDEPENDENS. Mutants lacking
      detectable VIP4 expression flower earlier than FLC null mutants, suggesting that
      VIP4 regulates flowering-time genes in addition to FLC. Floral morphology is also
      disrupted in vip4 mutants; thus, VIP4 has multiple roles in development.

PMID- 12207657
TI  - Carbon allocation to the insoluble fraction, respiration and triose-phosphate
      cycling in the sugarcane culm.
AB  - The changes in carbon allocation to non-sucrose metabolic pathways were
      investigated in developing internodes of sugarcane. Radiolabelling studies were
      done on internode 3, 6 and 9 tissues, representing three stages of increasing
      maturity. Carbon partitioning into sucrose increased from 34% of total 14C uptake
      in internode 3, to 66% in internodes 9. In immature tissue, the protein and fibre
      components were the dominant competing sinks with sucrose for incoming carbon, to
      which 14 and 16% of carbon was allocated. Increased carbon allocation to sucrose
      with tissue maturity coincided with a decrease in partitioning to fibre and total
      respiration. Between internodes 3 and 9 carbon allocation to total respiration
      decreased by 9%, and to fibre by 14%. Carbon cycling between the triose- and
      hexose phosphate pools was evident in all internodes. More than 90% of carbon
      entering triose-phosphates was returned to hexose in internode 3 tissue, and this
      flux decreased with tissue maturity.

PMID- 12207658
TI  - Allelochemical stress produced by the aqueous leachate of Callicarpa acuminata:
      effects on roots of bean, maize, and tomato.
AB  - The in vitro effects of an aqueous leachate (1%) of Callicarpa acuminata Kunth.
      (Verbenaceae) on radicle growth, protein expression, catalase activity, free
      radical production and membrane lipid peroxidation in roots of bean, maize, and
      tomato were examined. Aqueous extract of C. acuminata inhibited the radicle
      growth of tomato by 47%, but had no effect on root growth of maize and beans. 2D
      PAGE and densitometry analysis showed that C. acuminata aqueous leachate modified
      the expression of various proteins in the roots of all treated plants. In treated
      bean roots, microsequencing analysis of an 11.3-kDa protein, whose expression was
      enhanced by leachate treatment, revealed a 99% similarity with subunits of alpha
      amylase inhibitor of other beans. A 27.5-kDa protein induced in treated tomato
      showed 69-95% similarity to glutathione-S-transferases (GST) of other Solanaceae.
      Spectrophotometric analysis and native gels revealed that catalase activity was
      increased by 2.2-fold in tomato roots and 1.4-fold in bean roots. No significant
      changes were observed in treated maize roots. Luminol chemiluminescence levels, a
      measure of free radicals, increased 3.8-fold in treated tomato roots and 2.1-fold
      in treated bean roots. Oxidative membrane damage in treated roots was measured by
      lipid peroxidation rates. In tomato we observed a 2.4-fold increase in
      peroxidation, however, no effect was observed in maize or beans.

PMID- 12207659
TI  - Differential gene expression in proteoid root clusters of white lupin (Lupinus
      albus).
AB  - Proteoid root clusters are induced by P deficiency in white lupin. In their
      mature stage, these roots excrete organic acids (mainly citrate), thus allowing
      this species to acquire P from sparingly soluble sources. To screen for P
      regulated genes expressed during the period of citrate efflux, an experimental
      model based on proteoid root clusters contrasting in citrate efflux was
      developed. The feasibility of this model in identifying differential gene
      expression was assessed over a population of mRNAs from P-starved and P-starved
      rescued proteoid root clusters, sampled 24 and 72 h after P addition to 24 days P
      starved white lupin. Approximately 1500 bands of cDNA were displayed by
      differential display of 21-primer pair's combination; 52 differentially expressed
      bands, either up- or down-regulated after P addition, were observed. Sequence
      analysis of 17 of them revealed that they represent distinct cDNAs. A subsample
      of seven cDNAs was analysed by northern-blot, showing that six were truly
      differential products. Transcripts coding for enzymes involved in carbon flux
      (glyceraldehyde 3-phosphate dehydrogenase), glycolytic bypass
      (phosphoenolpyruvate carboxylase), Pi recycling (sulpholipid synthase), and two
      unknown cDNAs were shown to be down-regulated by P supply. Besides, an up
      regulated transcript coding for a putative auxin-induced protein was identified,
      whereas P addition did not significantly affect expression of a transcript for
      cyclophilins. These results show the feasibility of using P-starved and P-starved
      rescued proteoid root clusters as an experimental model to detect and examine the
      molecular changes occurring in root clusters during the period of citrate efflux
      in white lupin.

PMID- 12207660
TI  - Enhanced H+/ATP coupling ratio of H+-ATPase and increased 14-3-3 protein content
      in plasma membrane of tomato cells upon osmotic shock.
AB  - Modulation of proton extrusion and ATP-dependent H+ transport through the plasma
      membrane in relation to the presence of 14-3-3 proteins in this membrane in
      response to osmotic shock was studied in tomato (Lycopersicon esculentum Mill.
      cv. Pera) cell cultures. In vivo H+ extrusion by cells was activated rapidly and
      significantly after adding 100 mM NaCl, 100 mM KCl, 50 mM Na2SO4, 1.6% sorbitol
      or 2 micro M fusicoccin to the medium. The increase in H+ extrusion by cells
      treated with 100 mM NaCl was correlated with an increase of H+ transport by the
      plasma membrane H+-ATPase (EC 3.6.1.35), but not with changes in ATP hydrolytic
      activity of this enzyme, suggesting an increased coupling ratio of the enzyme.
      Immunoblot experiments showed increased amounts of 14-3-3 proteins in plasma
      membrane fractions isolated from tomato cells treated with 100 mM NaCl as
      compared to control cells without changing the amount of plasma membrane H+
      ATPase. Together, these data indicate that in tomato cells an osmotic shock could
      enhance coupling between ATP hydrolysis and proton transport at the plasma
      membrane through the formation of a membrane 14-3-3/H+-ATPase complex.

PMID- 12207661
TI  - Drought survival, summer dormancy and dehydrin accumulation in contrasting
      cultivars of Dactylis glomerata.
AB  - To study survival under prolonged and severe drought in the perennial grass
      Dactylis glomerata we compared dormant, resistant and sensitive cultivars (cvs.)
      in both field and glasshouse experiments. Water status, membrane stability and
      expression of dehydrins were assessed in the immature leaf bases, which are the
      last surviving organs. Analysis of leaf elongation and senescence of aerial
      tissues showed that dormancy was exhibited by the potentially dormant cultivar
      (cv.) only in the field. This cultivar exhibited a high survival rate, similar
      levels of dehydration and expression of a low-molecular weight (22-24 kDa)
      dehydrin in both drought and irrigated plants, whether fully dormant or not. At
      the same level of soil water deficit, there were no differences between the non
      dormant drought resistant and drought sensitive cultivars in plant water status
      and membrane stability. However, the accumulation of dehydrins as drought
      progressed was markedly different between these cultivars and was associated with
      their contrasting survival. The possible role of the major low-molecular
      dehydrins in maintenance of cell integrity under dehydration is discussed with
      reference to both summer dormancy and survival under severe drought.

PMID- 12207662
TI  - Differences in growth and nitrogen productivity between a stay-green genotype and
      a wild-type of Lolium perenne under limiting relative addition rates of nitrate
      supply.
AB  - The stay-green mutation of the nuclear gene sid inhibits chlorophyll degradation
      during leaf senescence in grasses. Decreased productivity is expected under
      conditions of limited external N availability, due to the higher retention of N
      in senescent tissues. However, this has not been reported when plants are grown
      at limiting low external concentrations of N. In the present study a different
      approach was taken, based on the relative addition rate method for defining
      limiting N supply. Wild-type and stay-green genotypes of Lolium perenne L. were
      grown for 30 days in flowing solution culture and then supplied with NO3- on an
      hourly basis over 35 days at relative addition rates (RARs) of 0.03, 0.06, 0.09
      and 0.12 day-1, ranging from severe N limitation to optimal supply. Plants were
      steady-state labelled with 15NO3- prior to RAR treatments, then switched to 14NO3
      to allow measurement of the re-distribution of N absorbed prior to RAR control.
      Following acclimation, relative growth rates (RGRs) approached the corresponding
      RAR, but were significantly lower for stay-green than wild-type at RARs of 0.03
      and 0.06 day-1. Tiller numbers were lower in stay-green plants after 35 days at
      all RARs except 0.12 day-1. Concentrations of total N in senescent laminae of
      stay-green plants exceeded those in wild-type plants by a similar margin (4.8-6.8
      mg g-1 DW) irrespective of RAR. Maximum nitrogen productivity (Pn) was 3.9 g DW g
      1 N day-1 (Nmin = 7.1 mg g-1 DW) in wild-type plants, and 5.1 g DW g-1 N day-1
      (Nmin = 10.7 mg g-1 DW) in stay-green plants. The higher N productivity of stay
      green plants indicated these plants used a smaller pool of metabolically
      available N more efficiently in biosynthesis compared with wild-type plants. The
      retention of N, absorbed prior to RAR treatments, in senescent laminae was
      significantly higher in stay-green plants at RAR of 0.03 day-1 after day 21 (i.e.
      20% versus 15% of the total N recovered). However, in terms of the whole N
      economy of the plant the margin represented only 1.7% of the total N content on
      day 35.

PMID- 12207663
TI  - Reduced atmospheric CO2 inhibits nitrogen mobilization in Festuca rubra.
AB  - In defoliated grasses, where photosynthesis is reduced due to removal of leaf
      material, it is well established that remobilization of nitrogen occurs from both
      older remaining leaves and roots towards the younger growing leaves. In contrast,
      little is known about the movement of nitrogen within intact grass plants
      experiencing prolonged inhibition of photosynthesis. We tested the following
      hypotheses in Festuca rubra L. ssp. rubra cv. Boreal: that both reduction of the
      atmospheric CO2 concentration and defoliation (1) induce mobilization of nitrogen
      from roots and older leaves towards growing leaves and (2) elicit similar
      directional change in the abundance of proteins in roots and older leaves
      relevant to the process of nitrogen mobilization including, glutamine synthetase
      (GS), EC 6.3.1.2; papain, EC 3.4.22.2; chymopapain, EC 3.4.22.6; ribulose
      bisphosphate carboxylase/oxygenase (Rubisco), EC 4.1.1.39; and the light
      harvesting complex of photosystem II (LHCPII). After growth at ambient
      atmospheric CO2 concentration, plants of F. rubra were subject to atmospheres
      containing either ambient (350 micro l l-1) or deplete (< 20 micro l l-1) CO2.
      Concurrently, plants were either left intact or defoliated on one occasion.
      Steady state 15N labelling coupled with a series of destructive harvests over a 7
      day period enabled changes in the nitrogen dynamics of the plants to be
      established. Proteins pertinent to the process of nitrogen mobilization were
      quantified by immunoblotting. Irrespective of defoliation, plants in ambient CO2
      mobilized nitrogen from older to growing leaves. This mobilization was inhibited
      by deplete CO2. Greater concentration of Rubisco and reduced chymopapain
      abundance in older remaining leaves of intact plants, in deplete compared with
      ambient CO2, suggested the inhibition of mobilization was due to inhibition of
      protein degradation, rather than to the export of degradation products. Both
      deplete CO2 and defoliation induced nitrogen mobilization from roots to growing
      leaves. In plants at ambient CO2, defoliation did not affect nitrogen uptake or
      its allocation. Therefore in F. rubra nitrogen mobilization can occur
      independently of any downregulation of nitrogen uptake. This suggests either
      different signal compounds may act to downregulate uptake and upregulate
      mobilization, or if one particular signalling compound is used its concentration
      threshold differs for induction of mobilization and downregulation of uptake. The
      abundance of the cysteine proteases papain and chymopapain was low in roots
      suggesting that they were not involved in protein degradation in this tissue.

PMID- 12207664
TI  - Transport interactions between cadmium and zinc in roots of bread and durum wheat
      seedlings.
AB  - Field studies have shown that the addition of Zn to Cd-containing soils can help
      reduce accumulation of Cd in crop plants. To understand the mechanisms involved,
      this study used 109Cd and 65Zn to examine the transport interactions of Zn and Cd
      at the root cell plasma membrane of bread wheat (Triticum aestivum L.) and durum
      wheat (Triticum turgidum L. var. durum). Results showed that Cd2+ uptake was
      inhibited by Zn2+ and Zn2+ uptake was inhibited by Cd2+. Concentration-dependent
      uptake of both Cd2+ and Zn2+ consisted of a combination of linear binding by cell
      walls and saturable, Michaelis-Menten influx across the plasma membrane.
      Saturable influx data from experiments with and without 10 micro m concentrations
      of the corresponding inhibiting ion were converted to double reciprocal plots.
      The results revealed a competitive interaction between Cd2+ and Zn2+, confirming
      that Cd2+ and Zn2+ share a common transport system at the root cell plasma
      membrane in both bread and durum wheat. The study suggests that breeding or
      agronomic strategies that aim to decrease Cd uptake or increase Zn uptake must
      take into account the potential accompanying change in transport of the competing
      ion.

PMID- 12207665
TI  - In vitro regeneration and genetic transformation of the berberine-producing
      plant, Thalictrum flavum ssp. glaucum.
AB  - Protocols have been developed for the in vitro regeneration and Agrobacterium
      mediated genetic transformation of meadow rue, Thalictrum flavum ssp. glaucum.
      Ten-day-old seedlings were bisected along the embryonic axis and the cotyledons
      were co-cultured with various Agrobacterium tumefaciens strains for 3 days. The
      cotyledons were cultured on a shoot induction medium (B5 salts and vitamins, 30 g
      l-1 sucrose, 2 mg l-1 kinetin, and 3 g l-1 Gelrite) containing 25 mg l-1
      hygromycin B as the selection agent and 250 mg l-1 timentin to facilitate the
      elimination of Agrobacterium. Only the oncogenic A. tumefaciens strains A281 and
      C58 produced transgenic T. flavum callus tissues. A281 was the most effective
      strain producing hygromycin-resistant callus on 85% of the explants. Transgenic
      callus was subcultured on the shoot induction medium every 2 weeks. After 12
      weeks, hygromycin-resistant shoots that formed on explants exposed to strain A281
      were transferred to a root induction medium (B5 salts and vitamins, 25 mg l-1
      hygromycin B, 250 mg l-1 timentin, and 3 g l-1 Gelrite). Detection of the beta
      glucuronidase (GUS) gene using a polymerase chain reaction assay, the high levels
      of GUS mRNA and enzyme activity, and the cytohistochemical localization of GUS
      activity confirmed the genetic transformation of callus cultures and regenerated
      plants. The transformation process did not alter the normal content of berberine
      in transgenic roots or cell cultures; thus, the reported protocol is valuable to
      study the molecular and metabolic regulation of protoberberine alkaloid
      biosynthesis.

PMID- 12207666
TI  - Characterization of a novel rice gene OsATX and modulation of its expression by
      components of the stress signalling pathways.
AB  - In our search to identify gene(s) involved in the rice self-defense responses, we
      cloned a novel rice (Oryza sativa L. cv. Nipponbare) gene, OsATX, a single copy
      gene, from the JA treated rice seedling leaves cDNA library. This gene encodes a
      69 amino acid polypeptide with a predicted molecular mass of 7649.7 and a pI of
      5.6. OsATX was responsive to cutting (wounding by cutting the excised leaf), over
      its weak constitutive expression in the healthy leaves. The critical signalling
      molecules, jasmonic acid (JA), salicylic acid (SA), abscisic acid (ABA), and
      hydrogen peroxide, together with protein phosphatase inhibitors, effectively up
      regulated the OsATX expression with time, over the excised leaf cut control,
      whereas ethylene had no affect. Furthermore, copper, a heavy metal, also up
      regulated OsATX expression. Moreover, induced expression of OsATX mRNA was
      influenced by light signal(s), and showed a requirement for de novo synthesized
      protein factors. Additionally, co-application of either JA or ABA with SA
      drastically suppressed the induced OsATX mRNA level. Finally, the blast pathogen,
      Magnaporthe grisea, triggered OsATX mRNA accumulation. These results strongly
      suggest a function/role(s) for OsATX in defense/stress responses in rice.

PMID- 12207667
TI  - Drought regulation of GST8, encoding the Arabidopsis homologue of ParC/Nt107
      glutathione transferase/peroxidase.
AB  - Glutathione transferases (GST; EC 2.5.1.18) have been involved in many biotic and
      abiotic interactions of plants with their environment, but very little
      information is available on their regulation and possible role in drought
      tolerance. The GST8 gene of Arabidopsis thaliana encodes, as assessed by
      phylogenetic analysis, the homologue of an extremely conserved subgroup of Tau
      GSTs. During rapid dehydration of seedlings and progressive drought stress of
      mature plants, GST8 transcript levels increased following slower kinetics than
      RNAs for dehydration responsive genes RD29A and B, and strictly paralleled, in a
      mostly ABA independent manner, expression of oxidative stress marker PRX. GST8
      RNA levels were also consistently increased by oxidative stress, high doses of
      auxin or cytokinin, and to a lesser extent, by wounding. RNA levels of ERD13, a
      previously described rapid dehydration responsive GST of the Phi class, were not
      co-regulated with those of GST8. Our results suggest that a drought-associated
      oxidative stress induces accumulation of GST8, whose function could be to
      counteract the effect of higher ROS production in stressed plants

PMID- 12207668
TI  - Phenylalanine ammonia lyase gene expression during abscission in citrus.
AB  - Phenylalanine ammonia lyase (PAL) gene expression was examined in fruit and leaf
      abscission zones of Valencia orange for periods up to 72 h after induction of
      abscission with Ethrel(R) (CEPA) or the citrus mature fruit-specific abscission
      material 5-chloro-3-methyl-4-nitro-1H-pyrazole (CMN-P). PAL gene expression was
      detected in mature fruit abscission zones beginning 6 and 24 h after CEPA and CMN
      P application, respectively, and continued up to 72 h. PAL gene expression was
      detected in leaf abscission zones 6 h after CEPA application and continued
      throughout the remainder of the study. In contrast, PAL gene expression was not
      detected in leaf abscission zones treated with CMN-P. 2-aminoindan-2-phosphonic
      acid (AIP), a specific inhibitor of PAL enzyme activity, decreased CMN-P-induced
      PAL expression in fruit abscission zones, and this was accompanied by a lack of
      fruit drop. PAL transcripts were low in abscission zones of immature fruit;
      however, the transcript was induced by CMN-P but less by CEPA application. The
      data suggest that downstream products of PAL activity may be important not only
      for wound healing and defense reactions that occur at the abscission zone
      fracture plane, but also for regulation of PAL gene expression during abscission.

PMID- 12207669
TI  - Studies on callose and cutin during the expression of competence and
      determination for organogenic nodule formation from internodes of Humulus lupulus
      var. Nugget.
AB  - Callose and cutin deposition were followed by staining with Aniline Blue and Nile
      Red and by immunolocalization using antibodies raised against callose. Along with
      morphogenesis induction from internodes of Humulus lupulus var. Nugget, a
      temporal and spatial differential deposition of callose and cutin was observed. A
      cutin layer showing bright yellow autofluorescence appears, surrounding cells or
      groups of cells committed to express morphogenic competence. This cutin layer
      that evolves to a randomly organized network appeared underneath a callose layer
      and may create a specific cellular environment with altered permeability and
      altered receptors providing conditions for entering the cell cycle. The incipient
      callose accumulation in control explants cultured on basal medium suggests the
      involvement of callose in the initiation of the morphogenic programme leading to
      nodule formation. A scanning electron microscopic study during the organogenic
      process showed that before shoot bud regeneration, the cutin layer increases in
      thickness and acquires a smooth texture. This cutin layer is specific to nodular
      organogenic regions and disappeared with plantlet regeneration. This layer may
      control permeability to water and solute transfer throughout plantlet
      regeneration.

PMID- 12207670
TI  - Regulation of the xanthophyll cycle pool size in duckweed (Lemna minor) plants.
AB  - Duckweed (Lemna minor L.) plants grown under high light are characterized, when
      compared to low light acclimated plants, by a higher xanthophyll cycle (VAZ) pool
      content, but also by a higher proportion of photoconvertible violaxanthin and a
      superior ability to synthesize VAZ pigments. When duckweed plants were
      transferred to a high light environment a general response was the quick
      adjustment of the carotenoid composition, mainly xanthophyll cycle pigments.
      These changes resulted from a balance between a process of continuous light
      independent carotenoid degradation and a light-induced accumulation. The use of
      norflurazon, an inhibitor of carotenogenesis, allowed us to demonstrate that the
      observed light induced increase of the VAZ pool was mainly caused by de novo
      synthesis through carotenogenesis. The extent of light-induced carotenogenesis
      was proportional to the light treatment and also to the operation of the VAZ
      cycle since it was partly abolished by treatments leading to a low activity of
      the VAZ cycle, such as low light, DTT or DCMU. These results suggest that not
      only the light itself, but also a mechanism triggered by a factor associated with
      the de-epoxidation state of the VAZ cycle controls carotenogenesis at some point
      before phytoene formation in the terpenoid biosynthesis pathway.

PMID- 12207671
TI  - Profiles of photosynthesis within red and green leaves of Quintinia serrata.
AB  - We have measured photosynthesis at the cellular, tissue, and whole leaf levels to
      understand the role of anthocyanin pigments on patterns of light utilization.
      Profiles of chlorophyll fluorescence through sections of red and green leaves of
      Quintinia serrata showed that anthocyanins in the mesophyll restricted absorption
      of green light to the uppermost palisade mesophyll. The distribution was further
      restricted when anthocyanins were also present in the upper epidermis. Mesophyll
      cells located beneath a cyanic light-filter assumed the characteristic
      photosynthetic features of shade-adapted cells. As a result, red leaves showed a
      23% reduction in CO2 assimilation under light-saturating conditions, and a lower
      threshold irradiance for light-saturation, relative to those of green leaves. The
      photosynthetic characteristics of red leaves are comparable to those of shade
      acclimated plants.

PMID- 12207672
TI  - Repair of cyclobutyl pyrimidine dimers in human skin: variability among normal
      humans in nucleotide excision and in photorepair.
AB  - BACKGROUND/AIMS: Photoreactivation (PR) of cyclobutyl pyrimidine dimers (CPD) in
      human skin remains controversial. Recently Whitmore et al. (1) reported negative
      results of experiments using two photorepair light (PRL) sources on UV-irradiated
      skin of volunteers. However, their PRL sources induced substantial levels of
      dimers in skin, suggesting that the additional dimers formed could have obscured
      PR. We met a similar problem of dimer induction by a PRL source. We designed and
      validated a PRL source of sufficient intensity to catalyse PR, but that did not
      induce CPD, and used it to measure photorepair in human skin. METHODS AND
      RESULTS: Using a solar simulator filtered with three types of UV-filters, we
      found significant dimer formation in skin, quantified by number average length
      analysis using electrophoretic gels of isolated skin DNA. To prevent scattered UV
      from reaching the skin, we interposed shields between the filters and skin, and
      showed that the UV-filtered/shielded solar simulator system did not induce damage
      in isolated DNA or in human skin. We exposed skin of seven healthy human
      volunteers to 302 nm radiation, then to the improved PRL source (control skin
      areas were kept in the dark for measurement of excision repair). CONCLUSIONS:
      Using a high intensity PRL source that did not induce dimers in skin, we found
      that three of seven subjects carried out rapid photorepair of dimers; two carried
      out moderate or slow dimer photorepair, and three did not show detectable
      photorepair. Excision repair was similarly variable in these volunteers. Subjects
      with slower excision repair showed rapid photorepair, whereas those with rapid
      excision generally showed little or no photoreactivation.

PMID- 12207673
TI  - The effects of EGb 761 on lipid peroxide levels and superoxide dismutase activity
      in sunburn.
AB  - BACKGROUND/PURPOSE: Free oxygen radicals are involved in inflammatory skin
      reactions induced by ultraviolet B (UVB). In this study, the effect of a herbal
      antioxidant Ginkgo biloba extract (EGb 761) was investigated in UVB irradiated
      mice skin. METHODS: The study was carried out on four groups of mice (n = 6 in
      each group). The first group was a control group (G1). The second group (G2) was
      only exposed to acute UVB irradiation. The third group (G3) received 100
      mg/kg/day of EGb 761 orally for 5 days before UVB irradiation and the fourth
      group (G4) was given only a single dose of EGb 761 immediately after UVB
      irradiation. Eighteen hours after exposing to UVB, lipid peroxide levels, and
      superoxide dismutase (SOD) activities were studied and UVB damage was evaluated
      histopathologically according to "sun-burn cell count". RESULTS: The SOD
      activities and Malondialdehyde (MDA) levels in G2, G3 and G4 were found to be
      decreased significantly when compared with G1 (P < 0.05). The SOD activities of
      G3 and G4 were higher when compared with G2 (P < 0.05). The number of sunburn
      cells (SBCs) was the highest in G2. CONCLUSIONS: Our results suggest that EGb 761
      may have an important effect, both as a protective and therapeutic agent, in
      sunburn after UVB irradiation.

PMID- 12207674
TI  - Age dependence of ultraviolet light-induced erythema following narrow-band UVB
      exposure.
AB  - BACKGROUND/PURPOSE: A report in the literature suggests longer duration and
      greater intensity of late phase UVB erythema in older people. The aim of this
      study was to identify differences in minimum erythema dose (MED) and intensity of
      UV-induced erythema after narrow band UVB exposure between older and younger
      individuals in the late phase of UVB erythema. METHODS: Using the UVA/TL 01 UV
      skin tester (Waldmann Medizintechnik, Villingen-Schwenningen, Germany), MED was
      determined for narrow-band UVB exposure in 20 young subjects aging from 20-40,
      and 20 elderly subjects over 70 years of age. The intensity of UV-induced
      erythema was measured by chromametry (a*-value and L-value) and laser Doppler 48
      h after irradiation. Minimum erythema dose (MED) was additionally assessed
      visually. RESULTS: Elderly subjects showed no statistical different MED compared
      to younger subjects. However, the erythema intensity 48 h after narrow-band UVB
      exposure was significantly greater in the elderly. CONCLUSIONS: Narrow-band UVB
      therapy may, in case of over dosage, produce more intense erythema in the late
      phase of UVB erythema in old people than in younger individuals.

PMID- 12207675
TI  - Quantitative assessment of narrow-band UVB induced tanning during phototherapy in
      Korea.
AB  - BACKGROUND/PURPOSE: Narrow-band (TL-01) UVB lamps are being increasingly used for
      phototherapy of psoriasis and other dermatoses, for their excellent effect
      compared with broad-band UVB sources. Many patients receiving phototherapy have
      complained about the tanning effect of ultraviolet radiation especially in dark
      skinned ones. So we wished to know the degree of pigmentation induced by
      phototherapy during narrow-band UVB treatment. METHODS: A total of 20 psoriasis
      patients receiving narrow-band UVB phototherapy were included in this study. A
      Minolta spectrophotometer CM-2002 was used to measure pigmentation. All patients
      were evaluated for skin color every seventh day for 7 weeks. The L* value
      (luminance) gives information about the relative lightness ranging from total
      black to pure white. The a* value represents the balance between red and green,
      and the b* value between yellow and blue. RESULTS: The L* values which indicate
      luminance decreased continuously until the 5th week, when maximum tanning was
      obtained. Afterwards minimal change was observed until the 7th week. The change
      of a* and b* values also showed the pattern that was compatible with the above
      results. The mean individual typology angle of our subjects was 41.9 degrees,
      which indicated they fell into "light" group of constitutional skin color
      category. CONCLUSION: From this study, we found that pigmentation induced by
      narrow-band UVB phototherapy increased continuously until the 5th week and then
      did not progress. Our results provide standard data of skin pigmentation during
      narrow-band UVB phototherapy in Korean brown skin.

PMID- 12207676
TI  - Positive effect of using calcipotriol ointment with narrow-band ultraviolet B
      phototherapy in psoriatic patients.
AB  - BACKGROUND/PURPOSE: The successful use of narrow-band ultraviolet B (UVB)
      phototherapy for the management of psoriasis has prompted the examination of
      various combination treatments with narrow-band UVB. However, there have been
      contradictory reports on the effect of the calcipotriol-narrow-band UVB
      combination. This study was performed to compare the clinical efficacy of the
      calcipotriol-narrow-band UVB combination with narrow-band UVB alone. METHODS: Of
      the 28 psoriasis patients, 10 were treated with the calcipotriol-narrow-band UVB
      and 18 with narrow-band UVB alone. Phototherapy was done once daily three times a
      week and the dose was gradually increased in a stepwise fashion by 0.05 J/cm2. At
      the end of therapy, overall efficacy was classified according to the chosen
      grading system. RESULTS: On assessing the therapeutic results using the criteria
      selected, 90.0% patients (n = 9) in the calcipotriol-narrow-band UVB group and
      61.1% patients (n = 11) in the narrow-band UVB group showed grade IV at the end
      of therapy. The calcipotriol-narrow-band UVB group showed more rapid improvement
      at the early stage. The final and total UVB dose were slightly lower in the
      calcipotriol-narrow-band UVB group but no significant difference was observed
      with respect to the total number of irradiations, duration of treatment, final
      UVB dose or total cumulative UVB dose required to reach grade IV in both groups
      (P > 0.05). The pattern of adverse effects was similar in both groups with a
      slightly higher frequency in the calcipotriol-narrow-band UVB group. CONCLUSION:
      Our results demonstrated that the total cumulative UVB dose required to reach
      grade IV was not significantly different in both groups, although it was slightly
      lower in the calcipotriol-narrow-band UVB group. However, a higher percentage of
      patients attained grade IV at the end of therapy in the combination group and
      this therapy was more effective in reducing the Psoriasis Area and Severity Index
      early in treatment. More studies are warranted to confirm these results.

PMID- 12207677
TI  - Ultraviolet protection factor of fabrics: comparison of laboratory and field
      based measurements.
AB  - BACKGROUND/PURPOSE: Spectrophotometry has become an accepted laboratory-based
      method for the determination of the ultraviolet protection factor (UPF) of
      fabrics. However, the validity of the UPF determined in the laboratory has been a
      controversial issue with regard to its significance in the field. To compare UPF
      values obtained by spectrophotometry, determination of the minimal erythema dose
      (MED), and biological dosimetry, we conducted laboratory and field-based
      measurements on various fabric materials. METHODS: One cotton, two viscose, and
      two polyester fabrics were enrolled into the study. Spectrophotometric (SP)
      testing was performed in accordance with the European standard. In vivo "on skin"
      (IV) testing on human subjects was performed with and without fabric protection.
      For determination of MED, a solar-simulator was used. In another part of the
      study, biological dosimetry (BD) testing was employed for laboratory testing with
      solar-simulated radiation (laboratory BD testing) as well as field-based
      measurements with natural sunlight in stationary (stationary BD testing) and
      "real life" exposure situations (mobile subject BD testing). For field-based
      measurements one light-weight polyester fabric was selected. RESULTS: The
      differences of the mean UPF values obtained by the laboratory-based methods were
      significant (MANOVA; P = 0.05), except for fabric no. 2 (MANOVA; P = 0.097). In 4
      of the 5 fabrics tested, UPF values obtained by IV testing were significantly
      lower than those obtained by SP testing (t-test; P = 0.05). In 3 fabrics, SP
      testing revealed significantly higher UPF values in comparison to laboratory BD
      testing (t-test; P = 0.05). The differences of UPF values obtained by the
      laboratory and field-based measurements employed for the light-weight polyester
      fabric were significant (ANOVA; P = 0.05). In comparison to SP testing (UPF 3.8),
      stationary BD testing resulted in significantly lower (UPF 3.5) and mobile
      subject BD testing in a significantly higher UPF of 4.4 (t-test; P = 0.05). The
      UPF obtained by mobile subject BD testing differed significantly from the UPF
      obtained by stationary BD testing (t-test; P = 0.05). CONCLUSIONS: Comparison of
      the presented methods indicates that IV testing generally results in lower UPF
      values. By contrast BD testing in "real life" exposure situations reveals
      relatively high UPF values. Although an overestimation of the
      spectrophotometrically measured UPF has been observed in comparative laboratory
      testing, UPF values obtained by field-based measurements are in relatively good
      agreement, or even surpass UPF values obtained by spectrophotometry. It is,
      therefore, suggested that SP testing provides "safe" UPF values which may be also
      valid in extreme real exposure situations. Biological UV dosimetry is, however, a
      promising alternative method for UPF testing: the test is easily performed in
      realistic exposure situations, the test is relatively inexpensive, and the
      measurements are valid.

PMID- 12207678
TI  - Photoimmunosuppression.
AB  - Ultraviolet (UV) radiation can exert a variety of biological effects, including
      induction of skin cancer, premature skin ageing and inhibition of the immune
      system. The immunosuppressive properties of UV radiation are of major biological
      relevance since suppression of the immune system by UV radiation is not only
      responsible for the exacerbation of infectious diseases following UV exposure,
      but also contributes to the induction of skin cancer. Hence, understanding of the
      mechanisms by which UV radiation compromises the immune system is of primary
      importance. UV radiation suppresses the immune system in multiple ways. It
      inhibits antigen presentation, stimulates the release of immunosuppressive
      cytokines and induces the generation of lymphocytes of the suppressor subtype. In
      the following, some of the basic mechanisms underlying UV-induced
      immunosuppression will be discussed.

PMID- 12207680
TI  - Erythropoietic protoporphyria (EPP) at 40. Where are we now?
AB  - Since Professor Magnus first defined erythropoietic protoporphyria (EPP) in 1961,
      there has been considerable progress in the understanding this disease. The past
      decade has been a period of spectacular progress in understanding the genetics
      and pathogenesis of the disease by molecular investigation. However, progress in
      therapy for EPP has been slower, and has been dogged by difficulty in assessing
      treatment efficacy in patients. We are now entering an era in which advances in
      molecular genetics are directly affecting patient management. This review
      summarises laboratory and clinical progress in EPP in the past 40 years, and
      assesses the potential impact of molecular biology on clinical practice.

PMID- 12207681
TI  - Sunscreen use and melanoma: a case of evidence-based prevention?
AB  - BACKGROUND: A preventive effect of sunscreens on melanoma development is still
      subject of intense discussion. The practical consequences for changes in public
      health campaigns are neglected in this debate. METHODS: An extensive literature
      search for studies on the association between sunscreen use and melanoma
      occurrence was performed. The principles of evidence-based medicine (EBM) are
      applied to the issue to derive at recommendations for an evidence-based
      prevention of melanoma. RESULTS: We identified 17 case-control studies providing
      risk estimates for the relationship under study. These risk estimates are too
      heterogeneous to allow a reasonable conclusion by summarizing the evidence. The
      application of the EBM approach yields therefore an inconclusive result: the
      melanoma protective potential of sunscreens cannot be proven using the existing
      evidence. The information necessary to fully assess the effect of sunscreen use
      on melanoma development is not currently available. CONCLUSION: Based on the
      current evidence the focus of recommendations for melanoma prevention in public
      awareness campaigns has to be changed. It should be much more emphasized to
      minimize exposure to ultraviolet (UV) radiation during peak hours, wear
      protective clothing, hats and UV-opaque sunglasses, seek shade and protect
      infants and children against too much UV radiation exposure at all than to use
      sunscreens.

PMID- 12207682
TI  - Chronic actinic dermatitis developed during phototherapy for psoriasis.
AB  - A patient with psoriasis vulgaris had been successfully treated with PUVA and UVB
      therapy. During maintenance phototherapy, he suddenly became photosensitive and
      developed eczematous eruption. Minimal response doses to UVB and UVA were
      extremely low--1.09 mJ/cm2 and 0.3 J/cm2, respectively. No chemical substances
      were identified as the responsible photosensitizer. The condition was diagnosed
      as chronic actinic dermatitis (CAD). PUVA therapy was unsatisfactory because it
      was not possible to administer an adequate dose of UVA. Oral cyclosporine,
      topical corticosteroid and sunscreen were used with beneficial therapeutic
      effects on psoriasis and CAD. As far as we know, the development of CAD during
      phototherapy has not been previously reported.

PMID- 12207683
TI  - Chronic actinic dermatitis: a case report and immunohistological analysis in its
      early phase.

PMID- 12207684
TI  - Polymorphous light eruption: is herpes virus the culprit?

PMID- 12207687
TI  - Iron transport and regulation, cell signalling and genomics: lessons from
      Escherichia coli and Pseudomonas.
AB  - A variety of bacterial species secrete and take up chelating compounds that
      enable acquisition of iron (siderophores). It has become clear that a common
      feature in regulation of different iron acquisition systems is the involvement of
      alternative sigma factor proteins of the extracytoplasmic function (ECF) family.
      Two of these proteins, PvdS from Pseudomonas aeruginosa and FecI from Escherichia
      coli K-12, have been studied extensively. PvdS directs transcription of genes
      required for the biosynthesis of a siderophore, pyoverdine, and FecI causes
      expression of genes for uptake of ferric citrate. FecI forms part of a signalling
      system that responds to the presence of ferric citrate. Here, we review recent
      advances in understanding of PvdS and of the Fec signalling system. PvdS and FecI
      are part of a distinct subfamily of ECF sigma factors involved in iron
      acquisition and hence named the iron-starvation sigmas. Analysis of microbial
      genome sequences shows that Fec-like signalling systems are present in a wide
      range of species and many such systems may be present in a single species. The
      availability of tools for large-scale genome analysis is likely to lead to rapid
      advances in our understanding of this expanding family of proteins.

PMID- 12207688
TI  - The dynamic microbe: green fluorescent protein brings bacteria to light.
AB  - The demonstration that the green fluorescent protein (GFP) from the jellyfish
      Aequorea victoria required no jellyfish-specific cofactors and could be expressed
      as a fluorescent protein in heterologous hosts including both prokaryotes and
      eukaryotes sparked the development of GFP as one of the most common reporters in
      use today. Over the past several years, the utility of GFP as a reporter has been
      optimized through the isolation and engineering of variants with increased
      folding rates, different in vivo stabilities and colour variants with altered
      excitation and emission spectral properties. One of the great utilities of GFP is
      as a probe for characterizing spatial and temporal dynamics of gene expression,
      protein localization and protein-protein interactions in living cells. The
      innovative application of GFP as a reporter in bacteria has made a significant
      contribution to microbial cell biology. This review will highlight recent studies
      that demonstrate the potential of GFP for real-time analysis of gene expression,
      protein localization and the dynamics of signalling transduction pathways through
      protein-protein interactions.

PMID- 12207689
TI  - The unfolding story of the Escherichia coli Hsp70 DnaK: is DnaK a holdase or an
      unfoldase?
AB  - We discuss recent experiments that have illuminated individual steps in the
      reaction cycle of the Escherichia coli Hsp70 molecular chaperone DnaK. Using this
      new information, we compare two distinctly different global mechanisms of action-
      holding versus unfolding--and argue that the available evidence suggests that
      DnaK is an unfoldase.

PMID- 12207690
TI  - Identification of novel hrp-regulated genes through functional genomic analysis
      of the Pseudomonas syringae pv. tomato DC3000 genome.
AB  - Pseudomonas syringae pv. tomato (Pst) strain DC3000 infects the model plants
      Arabidopsis thaliana and tomato, causing disease symptoms characterized by
      necrotic lesions surrounded by chlorosis. One mechanism used by Pst DC3000 to
      infect host plants is the type III protein secretion system, which is thought to
      deliver multiple effector proteins to the plant cell. The exact number of type
      III effectors in Pst DC3000 or any other plant pathogenic bacterium is not known.
      All known type III effector genes of P. syringae are regulated by HrpS, an NtrC
      family protein, and the HrpL alternative sigma factor, which presumably binds to
      a conserved cis element (called the "hrp box") in the promoters of type III
      secretion-associated genes. In this study, we designed a search motif based on
      the promoter sequences conserved in 12 published hrp operons and putative
      effector genes in Pst DC3000. Seventy-three predicted genes were retrieved from
      the January 2001 release of the Pst DC3000 genome sequence, which had 95% genome
      coverage. The expression of the 73 genes was analysed by microarray and Northern
      blotting, revealing 24 genes/operons (including eight novel genes), the
      expression of which was consistently higher in hrp-inducing minimal medium than
      in nutrient-rich Luria-Bertani broth. Expression of all eight genes was dependent
      on the hrpS gene. Most were also dependent on the hrpL gene, but at least one was
      dependent on the hrpS gene, but not on the hrpL gene. An AvrRpt2-based type III
      translocation assay provides evidence that some of the hrpS-regulated novel genes
      encode putative effector proteins.

PMID- 12207691
TI  - Dynamic distribution of BIMG(PP1) in living hyphae of Aspergillus indicates a
      novel role in septum formation.
AB  - Mutation of bimG, the major protein phosphatase 1 gene in Aspergillus nidulans,
      causes multiple cell cycle and hyphal growth defects that are associated with
      overphosphorylation of subcellular components. We have used functional
      translational fusions with the green fluorescent protein (GFP) to show that BIMG
      has at least four discrete locations within growing hyphae. Three of these
      locations, the hyphal tip, the spindle pole body and the nucleus, correlate with
      previously known requirements for bimG(PP1) in mitosis and hyphal growth and are
      highly dynamic. BIMG-GFP in the hyphal tip seemed to be associated with the
      plasma membrane and formed a collar of fluorescence within the apical dome. The
      distribution of nuclear BIMG-GFP varied depending on nutritional conditions; on
      poor medium, it concentrated more in the nucleolus than in the nucleoplasm,
      whereas on rich medium, it was more evenly distributed between the two nuclear
      regions. The association of BIMG-GFP with developing septa was transient, and we
      present evidence that BIMG phosphatase plays a direct role in septum formation,
      distinct from its role in mitosis. We conclude that, by being physically present
      at several sites, the BIMG phosphatase has roles in multiple cellular processes.

PMID- 12207692
TI  - Function in Escherichia coli of the non-catalytic part of RNase E: role in the
      degradation of ribosome-free mRNA.
AB  - RNase E contains a large non-catalytic region that binds RNA and the protein
      components of the Escherichia coli RNA degradosome. The rne gene was replaced
      with alleles encoding deletions in the non-catalytic part of RNase E. All the
      proteins are stable in vivo. RNase E activity was tested using a P(T7)-lacZ
      reporter gene, the message of which is particularly sensitive to degradation
      because translation is uncoupled from transcription. The non-catalytic region has
      positive and negative effectors of mRNA degradation. Disrupting RhlB and enolase
      binding resulted in hypoactivity, whereas disrupting PNPase binding resulted in
      hyperactivity. Expression of the mutant proteins in vivo anticorrelates with
      activity showing that autoregulation compensates for defective function. There is
      no simple correlation between RNA binding and activity in vivo. An allele
      (rne131), expressing the catalytic domain alone, was put under P(lac) control. In
      contrast to rne+,low expression of rne131 severely affects growth. Even with
      autoregulation, all the mutants are less fit when grown in competition with wild
      type. Although the catalytic domain of RNase E is sufficient for viability, our
      work demonstrates that elements in the non-catalytic part are necessary for
      normal activity in vivo.

PMID- 12207693
TI  - Double-stranded RNA-mediated gene silencing of cysteine proteases (falcipain-1
      and -2) of Plasmodium falciparum.
AB  - Malaria remains a public health problem of enormous magnitude, affecting over 500
      million people every year. Lack of success in the past in the development of new
      drug/vaccines has mainly been attributed to poor understanding of the functions
      of different parasite proteins. Recently, RNA interference (RNAi) has emerged as
      a simple and incisive technique to study gene functions in a variety of
      organisms. In this study, we report the results of RNAi by double-stranded RNA of
      cysteine protease genes (falcipain-1 and -2) in the malaria parasite, Plasmodium
      falciparum. Using RNAi directed towards falcipain genes, we demonstrate that
      blocking the expression of these genes results in severe morphological
      abnormalities in parasites, inhibition of parasite growth in vitro and
      substantial accumulation of haemoglobin in the parasite. The inhibitory effects
      produced by falcipain double-stranded (ds)RNAs are reminiscent of the effects
      observed upon administering E-64, a cysteine protease inhibitor. The parasites
      treated with falcipain's dsRNAs also show marked reduction in the levels of
      corresponding endogenous falcipain mRNAs. We also demonstrate that dsRNAs of
      falcipains are broken into short interference RNAs approximately 25 nucleotides
      in size, a characteristic of RNAi, which in turn activates sequence-specific
      nuclease activity in the malaria parasites. These results thus provide more
      evidence for the existence of RNAi in P. falciparum and also suggest
      possibilities for using RNAi as an effective tool to determine the functions of
      the genes identified from the P. falciparum genome sequencing project.

PMID- 12207694
TI  - Differential binding to and biofilm formation on, HEp-2 cells by Salmonella
      enterica serovar Typhimurium is dependent upon allelic variation in the fimH gene
      of the fim gene cluster.
AB  - Type 1 fimbria-mediated adherence to HEp-2 cells by two strains of Salmonella
      enterica serovar Typhimurium was found to be different. Although both strains
      exhibited a strong mannose-sensitive haemagglutination reaction with guinea pig
      erythrocytes, characteristic of the expression of type 1 fimbriae, only one of
      the strains adhered in large numbers to HEp-2 cells. Characterization of the fimH
      genes, encoding the fimbrial adhesins, indicated two allelic variants. Using fimH
      mutants of the two strains it was possible to demonstrate that binding to HEp-2
      cells was associated with the presence of one of the alleles regardless of the
      host strain. Therefore, this differential binding was not a function of the type
      I fimbrial shaft or the presence of other types of fimbriae produced by one
      strain but not the other. These observations may explain the differences in HEp-2
      binding by type 1 fimbriate strains of Salmonella previously reported by several
      groups. Also, our studies demonstrate that the FimH adhesin can influence the
      efficiency of biofilm formation on HEp-2 cells using once-flow-through continuous
      culture conditions. The formation of biofilms on eukaryotic cells using this
      procedure is more likely to represent those conditions found in the intestinal
      tract than conditions using batch culture techniques to investigate adherence and
      biofilm formation. Indeed, the increased efficiency of biofilm formation in the
      murine intestinal tract confirmed the role of one of the fimH alleles in this
      process.

PMID- 12207695
TI  - Antibiotics that inhibit cell wall biosynthesis induce expression of the Bacillus
      subtilis sigma(W) and sigma(M) regulons.
AB  - Bacillus subtilis encodes seven extracytoplasmic function (ECF) sigma factors.
      The sigma(W) regulon includes functions involved in detoxification and protection
      against antimicrobials, whereas sigma(M) is essential for growth at high salt
      concentrations. We now report that antibiotics that inhibit cell wall
      biosynthesis induce both sigma(W) and sigma(M) regulons as monitored using DNA
      microarrays. Induction of selected sigma(W)-dependent genes was confirmed using
      lacZ reporter fusions and Northern blot analysis. The ability of vancomycin to
      induce the sigma(W) regulon is dependent on both sigma(W) and the cognate anti
      sigma, RsiW, but is independent of the transition state regulator AbrB. These
      results suggest that the membrane-localized RsiW anti-sigma(W) factor mediates
      the transcriptional response to cell wall stress. Our findings are consistent
      with the idea that one function of ECF sigma factors is to coordinate antibiosis
      stress responses and cell envelope homeostasis.

PMID- 12207696
TI  - GeneChip expression analysis of the iron starvation response in Pseudomonas
      aeruginosa: identification of novel pyoverdine biosynthesis genes.
AB  - Upon iron restriction, the opportunistic pathogen Pseudomonas aeruginosa produces
      various virulence factors, including siderophores, exotoxin, proteases and
      haemolysin. The ferric uptake regulator (Fur) plays a central role in this
      response and also controls other regulatory genes, such as pvdS, which encodes an
      alternative sigma factor. This circuit leads to a hierarchical cascade of direct
      and indirect iron regulation. We used the GeneChip to analyse the global gene
      expression profiles in response to iron. In iron-starved cells,the expression of
      118 genes was increased at least fivefold compared with that in iron-replete
      cells, whereas the expression of 87 genes was decreased at least fivefold. The
      GeneChip data correlated well with results obtained using individual lacZ gene
      fusions. Strong iron regulation was observed for previously identified genes
      involved in biosynthesis or uptake of the siderophores pyoverdine and pyochelin,
      utilization of heterologous siderophores and haem and ferrous iron transport. A
      low-iron milieu led to increased expression of the genes encoding TonB, alkaline
      protease,PrpL protease, exotoxin A, as well as fumarase C, Mn-dependent
      superoxide dismutase SodA, a ferredoxin and ferredoxin reductase and several
      oxidoreductases and dehydrogenases. Iron-controlled regulatory genes included
      seven alternative sigma factors and five other transcriptional regulators.
      Roughly 20% of the iron-regulated genes encoded proteins of unknown function and
      lacked any conclusive homologies. Under low-iron conditions, expression of 26
      genes or operons was reduced in a DeltapvdS mutant compared with wild type,
      including numerous novel pyoverdine biosynthetic genes. The GeneChip proved to be
      a very useful tool for rapid gene expression analysis and identification of novel
      genes controlled by Fur or PvdS.

PMID- 12207697
TI  - Imp/OstA is required for cell envelope biogenesis in Escherichia coli.
AB  - In Gram-negative bacteria, all components of the outer membrane are synthesized
      in the cytoplasm or the cytoplasmic leaflet of the inner membrane and must thus
      traverse the inner membrane and the periplasm on the way to their final
      destination. In this study, we show Imp/OstA to have characteristics typical for
      proteins involved in envelope biogenesis. Imp is essential and forms a high
      molecular-weight disulphide-bonded complex in the outer membrane. Upon depletion
      of Imp, lipids and outer membrane proteins appear in a novel membrane fraction
      with higher density than the outer membrane. We propose Imp to be part of a
      targeting/usher system for components of the outer membrane.

PMID- 12207698
TI  - Nitric oxide scavenging and detoxification by the Mycobacterium tuberculosis
      haemoglobin, HbN in Escherichia coli.
AB  - Nitric oxide (NO), generated in large amounts within the macrophages, controls
      and restricts the growth of internalized human pathogen, Mycobacterium
      tuberculosis H37Rv. The molecular mechanism by which tubercle bacilli survive
      within macrophages is currently of intense interest. In this work, we have
      demonstrated that dimeric haemoglobin, HbN, from M. tuberculosis exhibits
      distinct nitric oxide dioxygenase (NOD) activity and protects growth and cellular
      respiration of heterologous hosts, Escherichia coli and Mycobacterium smegmatis,
      from the toxic effect of exogenous NO and the NO-releasing compounds. A
      flavohaemoglobin (HMP)-deficient mutant of E. coli, unable to metabolize NO,
      acquired an oxygen-dependent NO consumption activity in the presence of HbN. On
      the basis of cellular haem content, the specific NOD activity of HbN was nearly
      35-fold higher than the single-domain Vitreoscilla haemoglobin (VHb) but was
      sevenfold lower than the two-domain flavohaemoglobin. HbN-dependent NO
      consumption was sustained with repeated addition of NO, demonstrating that HbN is
      catalytically reduced within E. coli. Aerobic growth and respiration of a
      flavohaemoglobin (HMP) mutant of E. coli was inhibited in the presence of
      exogenous NO but remained insensitive to NO inhibition when these cells produced
      HbN, VHb or flavohaemoglobin. M. smegmatis, carrying a native HbN very similar to
      M. tuberculosis HbN, exhibited a 7.5-fold increase in NO uptake when exposed to
      gaseous NO, suggesting NO-induced NOD activity in these cells. In addition,
      expression of plasmid-encoded HbN of M. tuberculosis in M. smegmatis resulted in
      100-fold higher NO consumption activity than the isogenic control cells. These
      results provide strong experimental evidence in support of NO scavenging and
      detoxification function for the M. tuberculosis HbN. The catalytic NO scavenging
      by HbN may be highly advantageous for the survival of tubercle bacilli during
      infection and pathogenesis.

PMID- 12207699
TI  - Polyadenylation of Escherichia coli transcripts plays an integral role in
      regulating intracellular levels of polynucleotide phosphorylase and RNase E.
AB  - Polyadenylation in Escherichia coli has been implicated in the destabilization of
      a variety of transcripts. However, transiently increasing intracellular poly(A)
      levels has also been shown to stabilize the pnp and rne transcripts, leading to
      increased polynucleotide phosphorylase (PNPase) and RNase E levels respectively.
      Here, we show that the half-lives of both the pnp and rne transcripts are
      dependent on the intracellular level of polyadenylated transcripts. In addition,
      experiments using pnp-lacZ and rne-lacZ translational fusions demonstrate that
      the variations in transcript stability and protein levels arise from alterations
      in the autoregulation of both genes. Further support for this conclusion is
      provided by the fact that, in an rne mutant in which autoregulation is
      inactivated by deletion of most of the 5' untranslated region, variations in the
      level of polyadenylated transcripts no longer affect RNase E protein expression.
      Of even more interest is the fact that the presence of a functional degradosome
      is essential for RNase E to detect increased levels of poly(A). Thus, it appears
      that polyadenylation of transcripts in E. coli serves as a sensing mechanism by
      which the cell adjusts the levels of both RNase E and PNPase.

PMID- 12207700
TI  - Agrobacterium type IV secretion is a two-step process in which export substrates
      associate with the virulence protein VirJ in the periplasm.
AB  - Type IV secretion systems are virulence determinants in many bacteria and share
      extensive homology with many conjugal transfer systems. Although type IV systems
      and their homologues have been studied widely, the mechanism by which substrates
      are secreted remains unclear. In Agrobacterium, we show that type IV secretion
      substrates that lack signal peptides form a soluble complex in the periplasm with
      the virulence protein VirJ. Additionally, these proteins co-precipitate with
      constituents of the type IV transporter: the VirB pilus and the VirD4 protein.
      Our findings suggest that the substrate proteins localized to the periplasm may
      associate with the pilus in a manner that is mediated by VirJ, and suggest a two
      step process for type IV secretion in Agrobacterium. Our analyses of protein
      protein interactions in a variety of mutant backgrounds indicate that substrates
      are probably secreted independently of one another.

PMID- 12207701
TI  - Identification of Xenorhabdus nematophila genes required for mutualistic
      colonization of Steinernema carpocapsae nematodes.
AB  - One stage in the symbiotic interaction between the bacterium Xenorhabdus
      nematophila and its nematode host, Steinernema carpocapsae, involves the species
      specific colonization of the nematode intestinal vesicle by the bacterium. To
      characterize the bacterial molecular determinants that are essential for vesicle
      colonization, we adapted and applied a signature-tagged mutagenesis (STM) screen
      to this system. We identified 15 out of 3000 transposon mutants of X. nematophila
      with at least a 15-fold reduction in average vesicle colonization. These 15
      mutants harbour disruptions in nine separate loci. Three of these loci have
      predicted open reading frames (ORFs) with similarity to genes (rpoS, rpoE, lrp)
      encoding regulatory proteins; two have predicted ORFs with similarity to genes
      (aroA, serC) encoding amino acid biosynthetic enzymes; one, designated nilB
      (nematode intestine localization), has an ORF with similarity to a gene encoding
      a putative outer membrane protein (OmpU) in Neisseria; and three, nilA, nilC and
      nilD, have no apparent homologues in the public database. nilA, nilB and nilC are
      linked on a single 4 kb locus. nilB and nilC are > 104-fold reduced in their
      ability to colonize the nematode vesicle and are predicted to encode membrane
      localized proteins. The nilD locus contains an extensive repeat region and
      several small putative ORFs. Other than reduced colonization, the nilB, nilC and
      nilD mutants did not display alterations in any other phenotype tested,
      suggesting a specific role for these genes in allowing X. nematophila to
      associate with the nematode host.

PMID- 12207702
TI  - Repeat-induced point mutation (RIP) in Magnaporthe grisea: implications for its
      sexual cycle in the natural field context.
AB  - Repeat-induced point mutation (RIP) is a process that detects DNA duplications
      and peppers their sequences with C:G to T:A transitions in the sexual phase of
      the life cycle. So far, this unique mechanism has been identified as a currently
      active process in only two fungal species, Neurospora crassa and Podospora
      anserina. To determine whether a RIP-like process operates in the plant
      pathogenic fungus Magnaporthe grisea, the retrotransposon MAGGY and the
      hygromycin B phosphotransferase gene were introduced into the fungus as multiple
      transgenes and examined for sequence alterations after a cross. Frequent C:G to
      T:A transitions in the transgenes were found in the descendants, preferentially
      in (A/Tp)Cp(A/T)contexts, suggesting that a process similar to RIP functions in
      M.grisea. We also examined the sequence of another retrotransposon Pyret in six
      field isolates of M. grisea. Even though no perfect stage has been known in M.
      grisea under field conditions to date, RIP-like transitions were found in all the
      field isolates tested. Interestingly, the frequency of the transitions mostly
      correlated with the fertility of the isolates examined under laboratory
      conditions. These results imply that the sexual cycle of this fungus exists or
      existed in the natural field context.

PMID- 12207703
TI  - The ParB protein of Streptomyces coelicolor A3(2) recognizes a cluster of parS
      sequences within the origin-proximal region of the linear chromosome.
AB  - The mycelial prokaryote Streptomyces coelicolor A3(2) possesses a large linear
      chromosome (8.67 Mb) with a centrally located origin of replication (oriC).
      Recently, chromosome partitioning genes (parA and parB) and putative ParB binding
      sites (parS sequences) were identified in its genome. The S. coelicolor
      chromosome contains more parS sequences than any other bacterial chromosome
      characterized so far. Twenty of the 24 parS sequences are densely packed within a
      relatively short distance (approximately 200 kb) around oriC. A series of in
      vitro and in vivo experiments showed that S. coelicolor ParB protein interacts
      specifically with the parS sequences, albeit with a rather low affinity. Our
      results suggested that the binding of ParB is not only determined by the parS
      sequence, but also by the location of target DNA close to oriC. The unusually
      high number and close proximity to each other of the parS sites, together with in
      vivo and in vitro evidence that multiple ParB molecules may assemble along the
      DNA from an initial ParB-parS complex, suggest that a large DNA segment around
      the replication origin may form a massive nucleoprotein complex as part of the
      replication-partitioning cycle.

PMID- 12207704
TI  - Mechanism of membrane fluidity optimization: isothermal control of the Bacillus
      subtilis acyl-lipid desaturase.
AB  - The Des pathway of Bacillus subtilis regulates the expression of the acyl-lipid
      desaturase, Des, thereby controlling the synthesis of unsaturated fatty acids
      (UFAs) from saturated phospholipid precursors. Previously, we showed that the
      master switch for the Des pathway is a two-component regulatory system composed
      of a membrane-associated kinase, DesK, and a soluble transcriptional regulator,
      DesR, which stringently controls transcription of the des gene. Activation of
      this pathway takes place when cells are shifted to low growth temperature. Here,
      we report on the mechanism by which isoleucine regulates the Des pathway. We
      found that exogenous isoleucine sources, as well as its alpha-keto acid
      derivative, which is a branched-chain fatty acid precursor, negatively regulate
      the expression of the des gene at 37 degrees C. The DesK-DesR two-component
      system mediates this response, as both partners are required to sense and
      transduce the isoleucine signal at 37 degrees C. Fatty acid profiles strongly
      indicate that isoleucine affects the signalling state of the DesK sensor protein
      by dramatically increasing the incorporation of the lower-melting-point anteiso
      branched-chain fatty acids into membrane phospholipids. We propose that both a
      decrease in membrane fluidity at constant temperature and a temperature downshift
      induce des by the same mechanism. Thus, the Des pathway would provide a novel
      mechanism to optimize membrane lipid fluidity at a constant temperature.

PMID- 12207705
TI  - Large-scale identification of serotype 4 Streptococcus pneumoniae virulence
      factors.
AB  - Streptococcus pneumoniae (the pneumococcus) is carried in the nasopharynx of
      healthy individuals, but can spread to other host sites and lead to pneumonia,
      bacteraemia, otitis media and meningitis. Although it is logical to think a
      priori that differential gene expression would contribute to the ability of this
      pathogen to colonize different sites, in fact very few genes have been
      demonstrated to play tissue-specific roles in virulence or carriage. Using
      signature-tagged mutagenesis to screen 6149 mariner-transposon insertion strains,
      we identified 387 mutants attenuated for infection in a murine model of
      pneumonia. Among these mutants are ones with disruptions in a number of putative
      tissue-specific transcriptional regulators, surface proteins, metabolic proteins
      and proteins of unknown function, most of which had not previously been
      associated with virulence. A subset of these, including most of those with
      insertions in putative transcriptional regulators,was examined for phenotypes in
      murine models of bacteraemia and nasopharyngeal carriage. Four classes of mutants
      defective in infection models of the: (I) lung, (II) lung and blood, (III) lung
      and nasopharynx,and (IV) all three tissues were identified, thus demonstrating
      the existence of tissue-specific pneumococcal virulence factors. Included in
      these strains were two with disruptions in a genetic locus that putatively codes
      for a transcriptional regulator, three surface proteins and three sortase
      homologues. Mutation analysis revealed that three of the seven genes in this
      locus are virulence factors that are specific to mucosal surfaces.

PMID- 12207706
TI  - Molecular analysis of tyrosine-and phenylalanine-mediated repression of the tyrB
      promoter by the TyrR protein of Escherichia coli.
AB  - The mechanism of repression of the tyrB promoter by TyrR protein has been studied
      in vivo and in vitro. In tyrR+ strains, transcription of tyrB is repressed by
      either tyrosine or phenylalanine. Both of the TyrR binding sites (strong and weak
      TyrR boxes) lie downstream of the tyrB transcription start site and are required
      for tyrosine- or phenylalanine-mediated repression. Our results establish that
      the binding of the TyrR protein to the weak box, induced by cofactor tyrosine or
      phenylalanine, is critical for repression to occur. Neither the binding of the
      TyrR protein dimer formed in the presence of phenylalanine, nor the binding of
      the hexamer formed in the presence of tyrosine, blocks the binding of RNA
      polymerase to the promoter. Instead, open complex formation is inhibited in the
      presence of tyrosine whereas a step(s) following open complex formation is
      inhibited in the presence of phenylalanine. Moving the TyrR boxes 3 bp or more
      further away from the promoter affects tyrosine-mediated repression without
      affecting phenylalanine-mediated repression which remains unaltered until 6 bp
      are inserted between the TyrR boxes and the promoter. Analysis of deletion and
      insertion mutants fails to reveal any face of the helix specificity for either
      tyrosine- or phenylalanine-mediated repression.

PMID- 12207707
TI  - Multiple bacteria encode metallothioneins and SmtA-like zinc fingers.
AB  - Zinc is essential but toxic in excess. Bacterial metallothionein, SmtA from
      Synechococcus PCC 7942, sequesters and detoxifies four zinc ions per molecule and
      contains a zinc finger structurally similar to eukaryotic GATA. The dearth of
      other reported bacterial metallothioneins has been surprising. Here we describe
      related bacterial metallothioneins (BmtA) from Anabaena PCC 7120, Pseudomonas
      aeruginosa and Pseudomonas putida that bind multiple zinc ions with high
      stability towards protons. Thiol modification demonstrates that cysteine
      coordinates zinc in all of these proteins. Additionally, (111)Cd-NMR, and (111)Cd
      edited (1)H-NMR, identified histidine ligands in Anabaena PCC 7120 BmtA,
      analogous to SmtA. A related Escherichia coli protein bound only a single zinc
      ion, via four cysteine residues, with low stability towards protons; (111)Cd-NMR
      and (111)Cd-edited (1)H-NMR confirmed exclusive cysteine-coordination, and these
      cysteine residues reacted rapidly with 5,5'-dithiobis-(2-nitrobenzoic acid). (1)H
      NMR of proteins from P. aeruginosa, Anabaena PCC 7120 and E. coli generated
      fingerprints diagnostic for the GATA-like zinc finger fold of SmtA. These studies
      reveal first the existence of multiple bacterial metallothioneins, and second
      proteins with SmtA-like lone zinc fingers, devoid of a cluster,and designated
      GatA. We have identified 12 smtA-like genes in sequence databases including four
      of the gatA type.

PMID- 12207708
TI  - The RHO1-GAPs SAC7, BEM2 and BAG7 control distinct RHO1 functions in
      Saccharomyces cerevisiae.
AB  - In Saccharomyces cerevisiae, the small GTPase RHO1 plays an essential role in the
      control of cell wall synthesis and organization of the actin cytoskeleton.
      Several regulators for RHO1 are known, including the GTPase-activating proteins
      (GAPs) SAC7 and BEM2. Here we show that BAG7, identified as the closest homologue
      of SAC7, also acts as a GAP for RHO1 in vitro and in vivo. Furthermore, we find
      that BAG7, SAC7, and BEM2 are functionally different in vivo. Overexpression of
      BAG7 or SAC7,but not BEM2, suppresses the cold sensitivity of a sac7 mutation and
      the lethality of RHO1 hyperactivation in response to cell wall damage. In
      contrast, overexpression of BEM2 or SAC7, but not BAG7, downregulates the RHO1
      controlled PKC1-MPK1 pathway, and disruption of BEM2 or SAC7, but not BAG7,
      results in increased MPK1 activation. We conclude that BEM2 and SAC7, but not
      BAG7, are involved in the control of the RHO1-mediated activation of MPK1,
      whereas BAG7 and SAC7, but not BEM2, are involved in the regulation of other RHO1
      functions. This suggests that different RHO1GAPs control different RHO1 effector
      pathways, thus ensuring their individual regulation at the appropriate place and
      time.

PMID- 12207709
TI  - Chromosome replication patterns in the hyperthermophilic euryarchaea
      Archaeoglobus fulgidus and Methanocaldococcus (Methanococcus) jannaschii.
AB  - We analysed chromosome replication patterns in the two hyperthermophilic
      euryarchaea Archaeoglobus fulgidus and Methanocaldococcus(Methanococcus)
      jannaschii by marker frequency analysis (MFA). For A. fulgidus, the central
      region of the chromosomal physical map displayed a higher relative abundance in
      gene dosage during exponential growth, with two continuous gradients to a region
      of lower abundance at the diametrically opposite side of the genome map. This
      suggests bidirectional replication of the A. fulgidus chromosome from a single
      origin. The organization of the putative replication origin region relative to
      the cdc6, mcm and DNA polymerase genes differed from that reported for Pyrococcus
      species. No single replication origin or termination regions could be identified
      for M. jannaschii, adding to the list of unusual properties of this organism. The
      organization of the A. fulgidus cell cycle was characterized by flow cytometry
      analysis of the samples from which genomic DNA was extracted for MFA. The
      relative lengths of the cell cycle periods were found to be similar to those of
      crenarchaea.

PMID- 12207710
TI  - Disruption of msl3 abolishes the synthesis of mycolipanoic and mycolipenic acids
      required for polyacyltrehalose synthesis in Mycobacterium tuberculosis H37Rv and
      causes cell aggregation.
AB  - Cell wall lipids of Mycobacterium tuberculosis containing multiple methylbranched
      fatty acids play critical roles in pathogenesis and thus offer targets for new
      antimycobacterial drugs. Mycocerosicacid synthase gene (mas) encodes the enzyme
      that produces one class of such acids. Seven mas-like genes (msls) were
      identified in the genome. One of them, msl3, originally annotated as two separate
      genes, pks 3 and pks 4, is now shown to constitute a single open reading frame,
      which encodes a 220.3 kDa protein. Msl3 was disrupted using a phage mediated
      delivery system and the gene replacement in the mutant was confirmed by
      polymerase chain reaction analysis of the flanking regions of the introduced
      disrupted gene and by Southern analysis. Biochemical analysis showed that the
      msl3 mutant does not produce mycolipanoic acids and mycolipenic(phthienoic)
      acids, the major constituents of polyacyl trehaloses and thus lacks this cell
      wall lipid, but synthesizes all of the other classes of lipids. The absence of
      the major acyl chains that anchor the surface-exposed acyltrehaloses causes a
      novel growth morphology; the cells stick to each other, most probably via the
      intercellular interaction between the exposed hydrophobic cell surfaces,
      manifesting a bead-like growth morphology without affecting the overall growth
      rate.

PMID- 12207711
TI  - Homoplasy and mutation model at microsatellite loci and their consequences for
      population genetics analysis.
AB  - Homoplasy has recently attracted the attention of population geneticists, as a
      consequence of the popularity of highly variable stepwise mutating markers such
      as microsatellites. Microsatellite alleles generally refer to DNA fragments of
      different size (electromorphs). Electromorphs are identical in state (i.e. have
      identical size), but are not necessarily identical by descent due to convergent
      mutation(s). Homoplasy occurring at microsatellites is thus referred to as size
      homoplasy. Using new analytical developments and computer simulations, we first
      evaluate the effect of the mutation rate, the mutation model, the effective
      population size and the time of divergence between populations on size homoplasy
      at the within and between population levels. We then review the few experimental
      studies that used various molecular techniques to detect size homoplasious events
      at some microsatellite loci. The relationship between this molecularly accessible
      size homoplasy size and the actual amount of size homoplasy is not trivial, the
      former being considerably influenced by the molecular structure of microsatellite
      core sequences. In a third section, we show that homoplasy at microsatellite
      electromorphs does not represent a significant problem for many types of
      population genetics analyses realized by molecular ecologists, the large amount
      of variability at microsatellite loci often compensating for their homoplasious
      evolution. The situations where size homoplasy may be more problematic involve
      high mutation rates and large population sizes together with strong allele size
      constraints.

PMID- 12207712
TI  - Phylogeographical approaches to assessing demographic connectivity between
      breeding and overwintering regions in a Nearctic-Neotropical warbler (Wilsonia
      pusilla).
AB  - We characterized the pattern and magnitude of phylogeographical variation among
      breeding populations of a long-distance migratory bird, the Wilson's warbler
      (Wilsonia pusilla), and used this information to assess the utility of mtDNA
      markers for assaying demographic connectivity between breeding and overwintering
      regions. We found a complex pattern of population differentiation in
      mitochondrial DNA (mtDNA) variation among populations across the breeding range.
      Individuals from eastern North America were differentiated from western
      individuals and the eastern haplotypes formed a distinct, well-supported cluster.
      The more diverse western group contained haplotype clusters with significant
      geographical structuring, but there was also broad mixing of haplotype groups
      such that no haplotype groups were population specific and the predominance of
      rare haplotypes limited the utility of frequency-based assignment techniques.
      Nonetheless, the existence of geographically diagnosable eastern vs. western
      haplotypes enabled us to characterize the distribution of these two groups across
      14 overwintering locations. Western haplotypes were present at much higher
      frequencies than eastern haplotypes at most overwintering sites. Application of
      this mtDNA-based method of linking breeding and overwintering populations on a
      finer geographical scale was precluded by the absence of population-specific
      markers and by insufficient haplotype sorting among western breeding populations.
      Our results suggest that because migratory species such as the Wilson's warbler
      likely experienced extensive gene flow among regional breeding populations,
      molecular markers will have the greatest utility for characterizing breeding
      overwintering connectivity at a broad geographical scale.

PMID- 12207713
TI  - Population genetic subdivision in the New Zealand greenshell mussel (Perna
      canaliculus) inferred from single-strand conformation polymorphism analysis of
      mitochondrial DNA.
AB  - Single-strand conformation polymorphism (SSCP) analysis of the NADH IV region of
      the mitochondrial DNA (mtDNA) molecule in greenshell mussels (Perna canaliculus)
      indicated strong population genetic structuring in this endemic New Zealand
      species. A northern and a southern group were differentiated by frequency shifts
      in common haplotypes and by the occurrence of a unique southern haplotype at
      approximately 20% frequency. This split occurred south of Cook Strait (the body
      of water between the North and the South Island) at approximately 42 degrees S
      latitude. Northern populations were less genetically diverse than southern
      populations and mussels from the west coast of the South Island were most
      distinct from northern mussels. We hypothesize that the unique haplotype VIII
      originated in the lower South Island, and that its spread northwards was
      obstructed by the opening of Cook Strait approximately 15 000-16 000 years ago
      and the subsequent establishment of present-day surface water circulation
      patterns in Greater Cook Strait. We suggest that present-day strong tidal flows
      and turbulent mixing of water masses in Cook Strait, and intense up-welling on
      the east and west coasts in this region, represent a barrier to gene flow between
      mussels located in the North Island and northern South Island vs. mussels in most
      of the South Island and Stewart Island.

PMID- 12207714
TI  - Genetic differentiation of the dengue vector, Aedes aegypti (Ho Chi Minh City,
      Vietnam) using microsatellite markers.
AB  - Dengue haemorrhagic fever emerged in the 1950s and has become a major public
      health concern in most Asian countries. In Vietnam, little is known about the
      intraspecific variation of the vector and its consequences on vectorial capacity.
      Here we report the use of microsatellite markers to differentiate Aedes aegypti
      populations in Ho Chi Minh City, a typical, overcrowded Asian city. Six
      microsatellite loci, with 5-14 alleles per locus, were scored in 20 mosquito
      samples collected in 1998 in Ho Chi Minh City. We found substantial
      differentiation among Ae. aegypti populations from the outskirts, whereas
      populations from the centre of the city showed less differentiation. These
      results are consistent with the hypothesis that populations of Ae. aegypti in
      central Ho Chi Minh City are panmictic because there are abundant larval breeding
      sites and an abundance of humans for adults to feed upon. In contrast,
      populations on the outskirts become differentiated largely through the processes
      of genetic drift because larval breeding sites are not as abundant. These
      findings implicate human activities associated with urbanization, as factors
      shaping the genetic structure of Ae. aegypti populations.

PMID- 12207715
TI  - Intraspecific molecular variation in the seaweed fly Coelopa frigida consistent
      with behavioural distinctness of British and Swedish populations.
AB  - The major aim of this study was to compare the intraspecific variation and
      genetic structure of the behaviourally distinct British and Swedish populations
      of the seaweed fly Coelopa frigida. C. frigida has been the subject of intense
      study into the basis of female choice. The behaviour of British females is
      consistent with a 'good genes' model, whereas that of the Swedish flies suggests
      a Fisher process, in which the difference between the former and the latter is
      defined by female choice increasing offspring viability in 'good genes' models.
      Through a study of variability in the mitochondrial cytochrome oxidase II gene
      from more than 600 flies, we show that there is clear differentiation at the
      molecular level between the two countries' populations, with an FST of > 75% and
      no shared haplotypes. Tajima's test reveals an excess of rare variants relative
      to expectation, which, if not the result of selective sweep, indicates either a
      population expansion or purifying selection against weakly deleterious variants.
      Within the two populations, substantial subpopulation differentiation is observed
      in the UK, where there is also evidence of isolation by distance. Swedish
      populations exhibit lower variability, and no evidence of isolation by distance,
      with the latter result possibly being related to the continuous distribution of
      suitable habitat. The pattern of intraspecific variation is explainable by a
      combination of contemporary and also historical factors. British and Swedish
      populations may have been descended from at least two separate founding
      populations during the recolonization of these areas following Pleistocene
      glaciations.

PMID- 12207716
TI  - Genetic diversity in natural and anthropogenic inland populations of salt
      tolerant plants: random amplified polymorphic DNA analyses of Aster tripolium L.
      (Compositae) and Salicornia ramosissima Woods (Chenopodiaceae).
AB  - Eight populations of Aster tripolium (Compositae) and six of Salicornia
      ramosissima (Chenopodiaceae) from inland, naturally salt-contaminated habitats
      and anthropogenic salt-polluted sites in central Germany (Thuringia, Anhalt
      Saxony) were analysed using random amplified polymorphic DNA (RAPD) markers to
      investigate the patterns of genetic variation. In both species, the genetic
      diversity observed in the younger, anthropogenic sites caused by potash mines
      during the last century was found to be not significantly lower than in the
      older, naturally salt-contaminated habitats. Therefore, it is speculated that the
      loss of genetic diversity caused by founder effects on the anthropogenic habitats
      was balanced by successive colonization events, actual gene flow between
      populations, or the rapid growth of populations on the secondary habitats after
      colonization. Analyses of molecular variance (amova) of the RAPD markers,
      neighbour-joining clustering of populations based on Reynolds' co-ancestry
      distances, and Mantel tests indicate that: (i) anthropogenic habitats were
      colonized independently; (ii) genetic differentiation among populations of S.
      ramosissima is more pronounced than in A. tripolium, which is considered to be
      mainly due to biological differences between the two species; and (iii) the
      geographical pattern of genetic diversity was considerably modulated by
      historical events and/or population genetic effects.

PMID- 12207717
TI  - Pollen movement in declining populations of California Valley oak, Quercus
      lobata: where have all the fathers gone?
AB  - The fragmented populations and reduced population densities that result from
      human disturbance are issues of growing importance in evolutionary and
      conservation biology. A key issue is whether remnant individuals become
      reproductively isolated. California Valley oak (Quercus lobata) is a widely
      distributed, endemic species in California, increasingly jeopardized by
      anthropogenic changes in biota and land use. We studied pollen movement in a
      savannah population of Valley oak at Sedgwick Reserve, Santa Barbara County, to
      estimate effective number of pollen donors (Nep) and average distance of
      effective pollen movement (delta). Using twogener, our recently developed hybrid
      model of paternity and genetic structure treatments that analyses maternal and
      progeny multilocus genotypes, we found that current Nep = 3.68 individuals. Based
      on an average adult density of d= 1.19 stems/ha, we assumed a bivariate normal
      distribution to model current average pollen dispersal distance (delta) and
      estimated delta= 64.8 m. We then deployed our parameter estimates in spatially
      explicit models of the Sedgwick population to evaluate the extent to which Nep
      may have changed, as a consequence of progressive stand thinning between 1944 and
      1999. Assuming that pollen dispersal distance has not changed, we estimate Nep
      was 4.57 individuals in 1944, when stand density was 1.48. Both estimates
      indicate fewer effective fathers than one might expect for wind-pollinated
      species and fewer than observed elsewhere. The results presented here provide a
      basis for further refinements on modelling pollen movement. If the trends
      continue, then ongoing demographic attrition could further reduce neighbourhood
      size in Valley oak resulting in increased risk of reproductive failure and
      genetic isolation.

PMID- 12207718
TI  - Capercaillie in the Alps: genetic evidence of metapopulation structure and
      population decline.
AB  - In the Alps, the capercaillie is distributed in a metapopulation pattern with
      local populations on mountain ranges separated by farmland valleys. Habitat
      deterioration, primarily related to human land use, resulted in population
      declines and range contractions became obvious. At the edge of a species' range,
      lower connectivity and less gene flow may render populations more susceptible to
      decline and extinction than in the core of the range. If this were true for the
      capercaillie in the Alps, edge populations should be subject to limited gene flow
      and should show genetic signs of a more severe population decline than core
      populations. To test this hypothesis, we used microsatellite DNA typing
      techniques. We assessed genetic variation within and among 18 local capercaillie
      populations across the Alps in relation to geographical distribution within the
      metapopulation system. All populations showed high levels of genetic variation in
      terms of average number of alleles, allelic richness and heterozygosity. Excess
      heterozygosity suggested a recent population decline, that was more pronounced in
      edge than core populations. We found high gene flow, but also significant
      differentiation among populations. Differentiation among edge populations was
      related to geographical distance, and appeared to be a recent process, most
      probably caused by reduced gene flow after population decline. In the core group,
      the high mountains of the central Alps seem to limit dispersal, and genetic drift
      was the most likely explanation for the observed differentiation among
      populations. We conclude that maintaining connectivity within the metapopulation
      system is vital for capercaillie conservation in the Alps.

PMID- 12207719
TI  - Population differentiation and nuclear gene flow in the Dominican anole (Anolis
      oculatus).
AB  - Allele frequency data from nuclear microsatellite loci were used to investigate
      patterns of nuclear gene flow and population structure in the morphologically
      variable Dominican anole (Anolis oculatus). All six loci used proved to be highly
      polymorphic, with an average of 18.8 alleles per locus. Test for Hardy-Weinberg
      equilibrium revealed small numbers of heterozygote deficiencies at single loci in
      single populations and consistent patterns of increasingly significant
      heterozygote deficiency in global tests across populations and loci. No
      significant relationship between FST and patristic distances estimated from
      mitochondrial DNA sequences was detected and estimates of FIS were significantly
      higher in females than in males, indicating that gene flow may be sex-biased and
      mediated mainly by male migration. A highly significant correlation between
      linearized FST and loge (geographical distance) indicates that geographical
      proximity is a significant factor in the genetic structure of A. oculatus
      populations. However, levels of gene flow between morphologically differentiated
      parapatric populations are frequently seen to be relatively high. This supports
      the hypothesis of natural selection being the driving force behind the
      development and maintenance of morphological variation and shows that adaptive
      differentiation may be maintained despite the homogenizing influence of gene
      flow. Generally, the morphologically variable populations of A. oculatus are seen
      to be poor candidates for in situ speciation, but an exceptional case on the west
      coast of Dominica indicates that isolation resulting from vicariant events may
      lead to rapid differentiation at both mitochondrial and nuclear loci. This
      provides a possible mechanism for anole speciation on other Caribbean islands.

PMID- 12207720
TI  - Population genetic structure of the cyclic snowshoe hare (Lepus americanus) in
      southwestern Yukon, Canada.
AB  - Spatial population structure has important ecological and evolutionary
      consequences. Little is known about the population structure of snowshoe hares
      (Lepus americanus), despite their ecological importance in North American boreal
      forests. We used seven variable microsatellite DNA loci to determine the spatial
      genetic structure of snowshoe hares near Kluane Lake, Yukon during a cyclic
      population peak. We sampled 317 hares at 12 sites separated by distances ranging
      from 3 to 140 km, and used 46 additional samples from Alaska and Montana. The
      level of genetic variation was high (13.4 alleles/locus, 0.67 expected
      heterozygosity) and the distribution of alleles and genotypes was not homogeneous
      across the sites. The degree of differentiation was low among Yukon sites (FST =
      0.015) and between Yukon and Alaska (FST = 0.012), but the Montana site was
      highly differentiated (FST = 0.20). A weak pattern of isolation by distance was
      found over the Yukon study area, with an indication that local genetic drift may
      be important in shaping the regional genetic structure. Landscape barriers
      expected to influence gene flow did not consistently affect genetic structure,
      although there was evidence for a partial barrier effect of Kluane Lake. The high
      level of inferred gene flow confirms that snowshoe hare dispersal is widespread,
      successful and equal between the sexes. A stepping-stone model of gene flow,
      potentially influenced by the synchronous density cycle, appears to best explain
      the observed genetic structure. Our results suggest that despite their dramatic
      fluctuations in density, snowshoe hares in the northern boreal forest have a
      large evolutionary effective population size and are not strongly subdivided by
      either physical or social barriers to gene flow.

PMID- 12207721
TI  - Likely multiple origins of a diploid hybrid sunflower species.
AB  - The recurrent origin of diploid hybrid species is theoretically improbable
      because of the enormous diversity of hybrid genotypes generated by recombination.
      Recent greenhouse experiments, however, indicate that the genomic composition of
      hybrid lineages is shaped in part by deterministic forces, and that recurrent
      diploid hybrid speciation may be more feasible than previously believed. Here we
      use patterns of variation from chloroplast DNA (cpDNA), nuclear microsatellite
      loci, cross-viability and chromosome structure to assess whether a well
      characterized diploid hybrid sunflower species, Helianthus anomalus, was derived
      on multiple occasions from its parental species, H. annuus and H. petiolaris.
      Chloroplast DNA and crossability data were most consistent with a scenario in
      which H. anomalus arose three times: three different H. anomalus fertility groups
      were discovered, each with a unique cpDNA haplotype. In contrast, there was no
      clear signature of multiple, independent origins from the microsatellite loci.
      Given the age of H. anomalus (> 100 000 years bp), it may be that microsatellite
      evidence for recurrent speciation has been eroded by mutation and gene flow
      through pollen.

PMID- 12207722
TI  - Late glacial history of the cold-adapted freshwater fish Cottus gobio, revealed
      by microsatellites.
AB  - The distribution of genetic diversity at 10 highly polymorphic microsatellite
      loci within the European freshwater fish, Cottus gobio, L. was examined. The
      sampling range comprised a large geographical scale including lineages known to
      be highly divergent at both mitochondrial DNA (mtDNA) and allozymes. An analysis
      of genetic variability within populations showed that expected heterozygosity and
      allelic richness could be explained largely by current effective population
      sizes. Evidence was found, however, that historical processes predating the last
      major glaciation affected allelic richness. In addition to confirming the large
      scale patterns from earlier studies, the microsatellite data revealed new
      insights into recent processes by analysing genetic structure within ancient
      lineages defined by mtDNA data. Stepwise mutation model (SMM) and nonSMM-based
      methods demonstrated a clear genetic structuring within the Northwestern European
      lineage comprising populations from Britain and Belgium, and within the Central
      European lineage populations from the rivers Danube, Elbe and Main. Supported by
      an analysis of genetic variability within populations these results showed that
      the bullhead populations most probably persisted throughout the last major
      glaciation within the British Isles and within the drainages of the rivers Elbe
      and Main. Such observations provide the first genetic evidence for a glacial
      refugium in such close proximity to the European glacial margins.

PMID- 12207723
TI  - Speciation and the establishment of zonation in an intertidal barnacle: specific
      settlement vs. selection.
AB  - The tropical barnacle Tetraclita forms a belt on hard substrates in the
      intertidal zone of the Red Sea. Based on morphological data, three distinct
      species were suggested to exist, occupying different vertical levels - T.
      barnesorum, T. rufotincta and T. achituvi. In this study we used molecular (12S
      mitochondrial ribosomal DNA) and ecological data to examine whether this
      morphological variability reflects genetic differences, or is a result of
      environmental factors. Adults and spats, collected from settlement plates, were
      censused and screened genotypically using single strand conformation polymorphism
      (SSCP) analysis, and settlement dynamics was recorded. We provide evidence for
      the existence of only two distinct species, and point out both phenotypic
      plasticity and convergence within and between the proposed species. Cyprids of T.
      achituvi settle specifically at the lower part of the Tetraclita belt, and
      feature one phenotype. In contrast, T. rufotincta, occupying the upper and middle
      portions of the Tetraclita belt, settles throughout the range, shows phenotypic
      plasticity (three variants), and presumably undergoes selection at the lower
      part. Thus, the vertical zonation of Tetraclita is produced by the combination of
      pre-settlement and post-settlement factors, in T. achituvi and T. rufotincta,
      respectively. The examined system may offer a model in which to study the
      mechanisms underlying sympatric speciation.

PMID- 12207724
TI  - Molecular phylogeography of common garter snakes (Thamnophis sirtalis) in western
      North America: implications for regional historical forces.
AB  - Complete ND2 and partial ND4 and cytochrome b mitochondrial DNA (mtDNA) sequences
      were analysed to evaluate the phylogeographic patterns of common garter snakes
      (Thamnophis sirtalis) in western North America. This species is widely
      distributed throughout North America, and exhibits extensive phenotypic variation
      in the westernmost part of its range. The overall phylogeographic pattern based
      on mtDNA sequences is concordant with results from studies of other species in
      this region, implicating historical vicariant processes during the Pleistocene
      and indicating bottleneck effects of recent dispersal into postglacial habitat.
      Indeed, the topology is statistically consistent with the hypothesis of both
      southern (Great Basin and California) and northern (Haida Gwaii) refugia.
      Specifically, we identified genetic breaks among three major clades: Northwest
      Coastal populations, Intermountain populations, and all California populations.
      The California clade contained the only other well-supported branching patterns
      detected; relationships among populations within the two northern clades were
      indistinguishable. These molecular splits contrast sharply with all prior
      geographical analyses of phenotypic variation in T. sirtalis in this region. Our
      results suggest that the extensive phenotypic variation in western T. sirtalis
      has been shaped more by local evolutionary forces than by shared common ancestry.
      Consequently, we consider all morphologically based subspecies designations of T.
      sirtalis in this region invalid because they do not reflect reciprocal monophyly
      of the mtDNA sequences.

PMID- 12207725
TI  - Phylogeography of western Pacific Leucetta 'chagosensis' (Porifera: Calcarea)
      from ribosomal DNA sequences: implications for population history and
      conservation of the Great Barrier Reef World Heritage Area (Australia).
AB  - Leucetta 'chagosensis' is a widespread calcareous sponge, occurring in shaded
      habitats of Indo-Pacific coral reefs. In this study we explore relationships
      among 19 ribosomal DNA sequence types (the ITS1-5.8S-ITS2 region plus flanking
      gene sequences) found among 54 individuals from 28 locations throughout the
      western Pacific, with focus on the Great Barrier Reef (GBR). Maximum parsimony
      analysis revealed phylogeographical structuring into four major clades (although
      not highly supported by bootstrap analysis) corresponding to the northern/central
      GBR with Guam and Taiwan, the southern GBR and subtropical regions south to
      Brisbane, Vanuatu and Indonesia. Subsequent nested clade analysis (NCA) confirmed
      this structure with a probability of > 95%. After NCA of geographical distances,
      a pattern of range expansion from the internal Indonesian clade was inferred at
      the total cladogram level, as the Indonesian clade was found to be the internal
      and therefore oldest clade. Two distinct clades were found on the GBR, which
      narrowly overlap geographically in a line approximately from the Whitsunday
      Islands to the northern Swain Reefs. At various clade levels, NCA inferred that
      the northern GBR clade was influenced by past fragmentation and contiguous range
      expansion events, presumably during/after sea level low stands in the
      Pleistocene, after which the northern GBR might have been recolonized from the
      Queensland Plateau in the Coral Sea. The southern GBR clade is most closely
      related to subtropical L. 'chagosensis', and we infer that the southern GBR
      probably was recolonized from there after sea level low stands, based on our NCA
      results and supported by oceanographic data. Our results have important
      implications for conservation and management of the GBR, as they highlight the
      importance of marginal transition zones in the generation and maintenance of
      species rich zones, such as the Great Barrier Reef World Heritage Area.

PMID- 12207726
TI  - Chloroplast DNA variation, postglacial recolonization and hybridization in hazel,
      Corylus avellana.
AB  - To unravel the postglacial migration history of hazel, Corylus avellana, the
      genetic variation at two types of chloroplast DNA markers, polymerase chain
      reaction-restriction fragment length polymorphism (PCR-RFLP) and microsatellites,
      was assessed in 26 natural hazel populations distributed across the range of C.
      avellana. In addition a sequence of 2468 base pairs, which contains the matK
      gene, was analysed in seven individuals. Very little variation was detected
      overall [hT:PCR-RFLP= 0.091, hT:microsatellite= 0.423, pi (nucleotide diversity)
      = 0.00093] but the microsatellite markers, which have the highest levels of
      variation, show a clear geographical structure that divides Europe into two
      areas: (i) Italy and the Balkans, on one hand and (ii) the rest of Europe, on the
      other hand. These data exclude Italy and the Balkans as possible origins of the
      postglacial recolonization but cannot unambiguously show which other area is the
      origin, since the genetic data does not indicate the direction of spread. If we
      take the pollen record into account, the most likely scenario would be an
      expansion from southwestern France into most of Europe except Italy and the
      Balkans, and then a local expansion in the latter area. The two main haplotypes
      identified with both PCR-RFLP and sequencing, A and B, were found not only in C.
      avellana but also in other European Corylus species and cultivars. Haplotype A,
      which is dominating all investigated natural populations of C. avellana, is also
      found in the European tree hazel (C. colurna) and haplotype B, which is rare in
      C. avellana, has been identified in the filbert (C. maxima) and C. avellana
      cultivars. This pattern seems to indicate a history of past hybridization among
      the European Corylus species and cultivars.

PMID- 12207727
TI  - Field experiments on the distributions of eggs of different phosphoglucomutase
      (PGM) genotypes in the yellow dung fly Scathophaga stercoraria (L.).
AB  - Female yellow dung flies can, in the laboratory, influence the probability that
      stored sperm from different males are used to fertilize eggs. This matches
      offspring phosphoglucomutase genotypes to the environmental conditions in which
      the larvae will grow, increasing larval growth success. We conducted field
      experiments in which dung topology or shading conditions were controlled. The
      proportions of the five common phosphoglucomutase alleles in eggs laid in north
      facing slopes or in shaded conditions was related to their electrophoretic
      mobility. We suggest that females lay eggs of different genotypes, by
      appropriately choosing their fathers, in different places.

PMID- 12207728
TI  - High levels of genetic monogamy in the group-living Australian lizard Egernia
      stokesii.
AB  - The Australian lizard Egernia stokesii lives in spatially and temporally stable
      groups of up to 17 individuals. We have recently shown that these groups are
      comprised of breeding partners, their offspring and, in some cases, highly
      related adults, providing the first genetic evidence of a family structure in any
      lizard species. Here we investigated the mating system of E. stokesii using data
      from up to eight polymorphic microsatellite loci and tested the hypothesis that
      breeding partners are monogamous both within and between mating seasons. Among 16
      laboratory-born litters from field collected gravid females from two sites in
      South Australia, 75% had a single male parent and no male contributed to more
      than one litter, indicating a high level of genetic monogamy within a season.
      Additional analyses of field caught individuals, captured between 1994 and 1998,
      enabled assignment of parentage for 70 juveniles and subadults. These data showed
      that most young (88.6%) had both parents from within the same group and that high
      proportions of males (88.9%) and females (63.6%) have multiple cohorts of
      offspring only with the same partner. Our results suggest that monogamy both
      within and between seasons is a common mating strategy of E. stokesii and that
      breeding partners maintain stable associations together and with multiple cohorts
      of their offspring over periods of up to at least 5 years.

PMID- 12207729
TI  - Anarchy in the UK: Detailed genetic analysis of worker reproduction in a
      naturally occurring British anarchistic honeybee, Apis mellifera, colony using
      DNA microsatellites.
AB  - Anarchistic behaviour is a very rare phenotype of honeybee colonies. In an
      anarchistic colony, many workers' sons are reared in the presence of the queen.
      Anarchy has previously been described in only two Australian colonies. Here we
      report on a first detailed genetic analysis of a British anarchistic colony. Male
      pupae were present in great abundance above the queen excluder, which was clearly
      indicative of extensive worker reproduction and is the hallmark of anarchy.
      Seventeen microsatellite loci were used to analyse these male pupae, allowing us
      to address whether all the males were indeed workers' sons, and how many worker
      patrilines and individual workers produced them. In the sample, 95 of 96 of the
      males were definitely workers' sons. Given that approximately 1% of workers' sons
      were genetically indistinguishable from queen's sons, this suggests that workers
      do not move any queen-laid eggs between the part of the colony where the queen is
      present to the area above the queen excluder which the queen cannot enter. The
      colony had 16 patrilines, with an effective number of patrilines of 9.85. The 75
      males that could be assigned with certainty to a patriline came from 7
      patrilines, with an effective number of 4.21. They were the offspring of at least
      19 workers. This is in contrast to the two previously studied Australian
      naturally occurring anarchist colonies, in which most of the workers' sons were
      offspring of one patriline. The high number of patrilines producing males leads
      to a low mean relatedness between laying workers and males of the colony. We
      discuss the importance of studying such colonies in the understanding of worker
      policing and its evolution.

PMID- 12207730
TI  - Investigation of the population genetic structure and mating system in the ant
      Pheidole pallidula.
AB  - The origin of eusociality in haplo-diploid organisms such as Hymenoptera has been
      mostly explained by kin selection. However, several studies have uncovered
      decreased relatedness values within colonies, resulting primarily from multiple
      queen matings (polyandry) and/or from the presence of more than one functional
      queen (polygyny). Here, we report on the use of microsatellite data for the
      investigation of sociogenetic parameters, such as relatedness, and levels of
      polygyny and polyandry, in the ant Pheidole pallidula. We demonstrate, through
      analysis of mother-offspring combinations and the use of direct sperm typing,
      that each queen is inseminated by a single male. The inbreeding coefficient
      within colonies and the levels of relatedness between the queens and their mate
      are not significantly different from zero, indicating that matings occur between
      unrelated individuals. Analyses of worker genotypes demonstrate that 38% of the
      colonies are polygynous with 2-4 functional queens, and suggest the existence of
      reproductive skew, i.e. unequal respective contribution of queens to
      reproduction. Finally, our analyses indicate that colonies are genetically
      differentiated and form a population exhibiting significant isolation-by
      distance, suggesting that some colonies originate through budding.

PMID- 12207731
TI  - The incidence and diversity of Wolbachia in gallwasps (Hymenoptera; Cynipidae) on
      oak.
AB  - Wolbachia bacteria infect approximately 20% of all insect species, and cause a
      range of alterations to host reproduction, including imposition of thelytoky. The
      incidence and phenotypic impact of Wolbachia remains to be established in many
      insect taxa, and considerable research effort is currently focused on its
      association with particular reproductive modes and the relative importance of the
      various pathways via which infection occurs. Gallwasps represent an attractive
      system for addressing these issues for two reasons. First, they show a diversity
      of reproductive modes (including arrhenotoky, thelytoky and cyclical
      parthenogenesis) in which the impact of Wolbachia infection can be examined.
      Second, they occupy two intimately linked trophic niches (gall-inducers and
      inquilines) between which there is potential for the horizontal exchange of
      Wolbachia infection. In the arrhenotokous gallwasp lineages screened to date (the
      herb-galling 'Aylacini' and the rose-galling Diplolepidini), Wolbachia infection
      always induces thelytoky. The impact of Wolbachia in other arrhenotokous clades,
      and in the cyclically parthenogenetic clades remains unknown. Here we use
      polymerase chain reaction (PCR) screening and sequence data for two Wolbachia
      genes (wsp and ftsZ) to examine the prevalence and incidence of Wolbachia
      infection in 64 species (a total of 609 individuals) in two further tribes: the
      arrhenotokous inquilines (tribe Synergini), and the cyclically parthenogenetic
      oak gallwasps (tribe Cynipini). We ask: (i) whether Wolbachia infection has any
      apparent impact on host reproduction in the two tribes and (ii) whether there is
      any correlation between Wolbachia infection and the apparent lack of an
      arrhenotokous generation in many oak gallwasp life cycles. We show: (i) that
      Wolbachia infection is rare in the Cynipini. Infected species show no deviation
      from cyclical parthenogenesis, and infection is no more common in species known
      only from a thelytokous generation; (ii) that there is a higher incidence of
      infection within the arrhenotokous inquilines, and generally in gallwasp tribes
      without cyclical parthenogensis; (iii) all Wolbachia-positive inquiline species
      are known to possess males, implying either that Wolbachia infection does not
      result in loss of sex in this tribe or, more probably, that (as for some rose
      gallwasps) Wolbachia infection leads to loss of sex in specific populations; and
      (iv) although we find some inquilines and gall inducers to be infected with
      Wolbachia having the same wsp sequence, these hosts are not members of the same
      gall communities, arguing against frequent horizontal transmission between these
      two trophic groups. We suggest that exchange may be mediated by the generalist
      parasitoids common in oak galls.

PMID- 12207732
TI  - Communities and populations of sebacinoid basidiomycetes associated with the
      achlorophyllous orchid Neottia nidus-avis (L.) L.C.M. Rich. and neighbouring tree
      ectomycorrhizae.
AB  - Several achlorophyllous orchids associate with ectomycorrhizal hymenomycetes
      deriving carbon from surrounding trees for the plant. However, this has not been
      shown for achlorophyllous orchids associating with species of Rhizoctonia, a
      complex of basal lineages of hymenomycetes that are the most common orchid
      partners. We analysed Neottia nidus-avis, an achlorophyllous orchid symbiotic
      with a Rhizoctonia, to identify its symbionts by internal transcribed spacer
      (ITS) sequencing. Analysis of 61 root systems from 23 French populations showed
      that N. nidus-avis associates highly specifically with a group of species of
      Sebacinaceae. Their diversity emphasizes the need for further investigations in
      the Sebacinaceae systematics. Sebacinoid ITS sequences were often identical
      within orchid populations and a trend to regional variation in symbionts was
      observed. Using ITS and intergenic spacer (IGS) polymorphism, we showed that each
      root system harboured a single species, but that several genets colonized it.
      However, no polymorphism of these markers was found among portions of each root:
      this is consistent with the putative mode of entry of the fungus, i.e. from the
      rhizome into roots but not repeatedly from the soil. In addition, ectomycorrhizae
      were always found within the N. nidus-avis root systems: 120 of the 144
      ectomycorrhizae typed by ITS sequencing were colonized by a sebacinoid fungus
      identical in ITS sequence to the respective orchid symbiont (even for the IGS
      polymorphism in some cases). Because sebacinoids were demonstrated recently to be
      ectomycorrhizal, the orchid is likely to derive its resources from surrounding
      trees, a mycorrhizal cheating strategy similar to other myco-heterotrophic plants
      studied to date.

PMID- 12207733
TI  - DNA sequence and RFLP data reflect geographical spread and relationships of
      Amylostereum areolatum and its insect vectors.
AB  - The white rot fungus, Amylostereum areolatum (Basidiomycetes), is best known for
      its symbiotic relationship with various siricid wood wasp species. In this study,
      the relationship between isolates of A. areolatum associated with two wood wasp
      species, Sirex noctilio and S. juvencus, are considered to identify possible
      intraspecific groups. Isolates from the northern (native) and southern (exotic)
      hemispheres are included to determine patterns of geographical spread and origin
      of introductions into the southern hemisphere. The phylogenetic relationships of
      these isolates to authentic isolates of A. chailletii, A. laevigatum and A.
      ferreum were also investigated. Sequence and restriction fragment length
      polymorphism (RFLP) analyses of the variable nuc-IGS-rDNA region provided markers
      to distinguish intraspecific groups within A. areolatum. Isolates of A. areolatum
      associated with S. noctilio and S. juvencus contained four heterogenic sequences
      in the DNA region analysed. These sequences occurred in one of five combinations
      in each isolate. Some of these sequences were unique to isolates of A. areolatum
      from either wasp species, while others were present in both groups. This shows
      the ancient and specialized evolutionary relationship that exists between these
      insects and fungi. Isolates from the southern hemisphere all share the same
      sequence group. This supports previous hypotheses that S. noctilio has spread
      between countries and continents of this region. At the interspecific level, the
      IGS-rDNA sequence analysis showed that A. ferreum and A. laevigatum are closely
      related to each other, and they in turn are related to A. chailletii.
      Amylostereum areolatum was the most distinctly defined species in the genus. This
      can be attributed to the obligate relationship between A. areolatum and its
      insect vectors. Polymerase chain reaction-RFLP analysis was also shown to be an
      effective tool to distinguish between the different species of Amylostereum.

PMID- 12207734
TI  - Molecular genecology of temperature response in Lolium perenne: 1. preliminary
      analysis to reduce false positives.
AB  - Molecular genecology is the study of geographical clines in frequencies of
      molecular markers and their relationship to ecological clines in environmental
      conditions. This study outlines the principles underlying the selection of
      populations, focusing on avoiding 'false positives'- noncausal correlations
      between allele frequency and the environment. The principles are illustrated by
      identifying a set of populations of Lolium perenne for the study of temperature
      responses. The selected set of populations encompasses a 20 degrees C range in
      mean January temperature. Their freezing tolerance shows a linear trend with
      winter temperature, LT50 decreasing by 0.25 degrees C for each 1 degrees C
      reduction in mean January temperature.

PMID- 12207735
TI  - Molecular genecology of temperature response in Lolium perenne: 2. association of
      AFLP markers with ecogeography.
AB  - Improved winter hardiness is an important breeding objective in the forage grass
      Lolium perenne. This is a complex trait with several components, including the
      ability to survive and grow at low temperature, to acclimate to cold, tolerate
      wind, snow cover and ice encasement. Marker-assisted selection has the potential
      to increase the efficiency of breeding for improved cold tolerance. Here we
      describe a genecological approach to identifying molecular markers that are
      associated with adaptation to low winter temperatures. AFLP was used to assess
      the genetic diversity in 29 wild populations of ryegrass (Lolium perenne)
      representing a pan-European temperature cline in terms of their geographical
      origin. A further 18 populations from a temperature cline in Bulgaria were also
      analysed. In addition, two varieties and five populations representing parents of
      mapping families currently in use at IGER were included in the analysis.
      Principal coordinate (PCoA) and cluster analyses of the molecular marker data
      showed that the Bulgarian altitude cline populations could be distinguished
      clearly from the other populations. Two regression analyses were carried out; one
      to identify AFLP markers that correlated in frequency with low mean January
      temperature of the geographical origin of the population, and another to identify
      AFLP markers correlating in frequency with the cold tolerance phenotype of the
      populations, as determined by LT50 values in freezing tests. In the first
      analysis six AFLP markers showed significant type II trends with mean January
      temperature, and in the second analysis 28 bands had a significant univariate
      relationship with the LT50 value of the accessions. In steps 2 and 3 of the
      stepwise analysis a further 4 and 5 bands, respectively, improved the fit
      significantly. The results of the two types of regression analysis are discussed
      in relation to ecogeography and cold tolerance phenotype of the populations.

PMID- 12207736
TI  - A genetic assessment of parentage in a natural population of dollar sunfish
      (Lepomis marginatus) based on microsatellite markers.
AB  - We employ microsatellite markers to assess mating tactics in Lepomis marginatus.
      Genetic assignments for 1015 progeny in 23 nests indicate that about 95% of the
      offspring were sired by their respective nest-guardians, a finding consistent
      with the apparent absence of a brood parasitic morphotype in this species.
      Allopaternal care was documented in two nests, one resulting from a nest
      takeover, the other from cuckoldry by an adjoining nest-tender. Clustered de novo
      mutations also were identified. About 2.5 females (range 1-7) contributed to the
      offspring pool within a typical nest. Results are compared to those for other
      Lepomis species.

PMID- 12207737
TI  - The value of molecular analysis by PCR in the diagnosis of cutaneous lymphocytic
      infiltrates.
AB  - The diagnosis and classification of cutaneous lymphomas remain a challenge for
      the clinician and dermatopathologist. This diagnostic dilemma is mainly
      encountered in the distinction between an early malignant lymphoma and a benign
      reactive lymphocytic infiltrate (pseudolymphoma). Until the beginning of the
      1980s, our diagnostic tools were limited to the clinical presentation, course,
      and histopathology in diagnosis and classification of lymphocytic infiltrates.
      Advances in immunology and, in particular, in molecular genetics with the
      introduction of the Southern blot technique and the polymerase chain reaction
      (PCR) have revolutionized the diagnosis of lymphocytic infiltrates by
      determination of clonality. In some series, more than 90% of cutaneous T-cell
      lymphomas have a clonal rearrangement of the T-cell receptor gamma-chain gene, as
      opposed to very low percentages of rearrangement in T-cell pseudolymphomas.
      However, the presence of clonality does not necessarily imply malignancy. Cases
      of pseudolymphomas, lichen planus and pityriasis lichenoides et varioliformis
      acuta were reported with clonal lymphocytic proliferations. Therefore, care
      should be exercised in the evaluation of the results of molecular analysis, and
      these should always be correlated with the clinical, histological and
      immunophenotypic picture to arrive at the correct diagnosis. It may be expected
      that the molecular methods for diagnosis of lymphocytic infiltrates will be
      improved and refined in future, and that sensitivity and specificity will
      increase.

PMID- 12207738
TI  - Three-dimensional imaging of human skin and mucosa by two-photon laser scanning
      microscopy.
AB  - BACKGROUND: Various structural components of human skin biopsy specimens are
      difficult to visualize using conventional histologic approaches. METHODS: We used
      two-photon microscopy and advanced imaging software to render three-dimensional
      (3D) images of in situ nerves, blood vessels, and hair follicles labeled with
      various fluorescent markers. Archived frozen human skin biopsy specimens were
      cryosectioned up to 150 micro m in thickness and fluorescently stained with
      rhodamine- or fluorescein-labeled antibodies or lectins. Optical sections were
      collected by two-photon microscopy and the resulting data sets were analyzed in
      three dimensions using Voxx software. RESULTS: Reconstructed image volumes
      demonstrated the complex 3D morphology of nerves, blood vessels and adnexal
      structures in normal mucocutaneous tissue. CONCLUSION: Two-photon microscopy and
      Voxx rendering software allow for detailed 3D visualization of structures within
      human mucocutaneous biopsy specimens, as they appear in situ, and facilitate
      objective interpretation of variations in their morphology. These techniques may
      be used to investigate disorders involving cutaneous structures that are
      difficult to visualize by means of traditional microscopy.

PMID- 12207739
TI  - Expression of CD44 and CD44v6 in primary cutaneous CD30 positive T-cell
      lymphoproliferative disorders.
AB  - BACKGROUND: Expression of the lymphocyte homing receptor CD44 and its variant
      form, CD44v6, have been linked to unfavorable prognosis and tumor dissemination
      in non-Hodgkin's lymphoma. The role of CD44 and CD44v6 in primary cutaneous
      lymphomas may not necessarily correlate with that observed in nodal lymphomas.
      Our study attempts to evaluate the expression pattern of CD44 and CD44v6 in
      primary cutaneous CD30 positive T-cell lymphoproliferative disorders including
      primary cutaneous anaplastic large cell lymphoma (cALCL) and lymphomatoid
      papulosis (LyP) and compared the expression between these two subgroups. METHODS:
      Immunohistochemical staining of CD44 and CD44v6 was performed on 10 cALCL and 18
      LyP cases. RESULTS: CD44 consistently expressed in all cases of primary cutaneous
      CD30 positive T-cell lymphoproliferative disorders. In contrast with previous
      studies, our results showed that CD44v6 expressed in 46% of all cases, including
      50% cALCL and 44% LyP. There was no statistic difference in expression of CD44 or
      CD44v6 between cALCL and LyP subgroups. CONCLUSIONS: These results provide a new
      evidence that CD44v6 is expressed in a subset cases of primary cutaneous CD30
      positive T-cell lymphoproliferative disorders and suggest that other factors or
      molecules rather than CD44 or CD44v6 are responsible for the difference between
      cALCL and LyP.

PMID- 12207740
TI  - Clinical and pathological spectrum of CD8-positive cutaneous T-cell lymphomas.
AB  - CD8+ T-cell lymphomas presenting in the skin are rare. We describe the clinical
      and histological features of 18 patients with CD8+ cutaneous T-cell tumors, which
      have been divided into four groups. Seven patients had precedent long histories
      of rashes, which progressively spread in a presentation similar to that of CD4+
      mycosis fungoides (MF). Three patients had long-standing localized plaques
      consistent with a pagetoid reticulosis (PR) pattern. Two patients presented with
      erythroderma and had peripheral blood involvement consistent with a Sezary
      syndrome (SS) pattern and had rapidly progressive clinical courses. Six patients
      presented with cutaneous nodules of varying sizes and had variable outcomes, with
      two having rapidly progressive disease, two with indolent recurrences and a
      further two with complete responses to treatment. Histologically, 12 of the 18
      cases showed an epidermotropic tumor infiltrate that was most marked in the three
      PR cases. Prominent periadnexal infiltration was seen in 11 cases. Similar to
      CD4+ MF, the skin-homing antigen, (cutaneous lymphocyte antigen: CLA), was
      strongly expressed in 13 of 16 tested cases. Expression of the cytotoxic granule
      protein granzyme B was noted in a majority of tumor cells in only three of 16
      tested cases. We conclude that approximately half of CD8+ cutaneous T-cell
      lymphomas clinically and histologically resemble CD4+ MF/SS, whereas presentation
      as discrete nodular lesions are more common in CD8+ tumors as compared to those
      that express CD4.

PMID- 12207741
TI  - Aberrant expression of p16 and RB protein in eccrine porocarcinoma.
AB  - BACKGROUND: Eccrine porocarcinoma is a rare malignant tumor of the sweat gland
      and very little is known about its etiology and molecular basis. METHODS: To
      investigate the expression of p16 and retinoblastoma (RB) protein and their
      relationship, an immunohistochemical method was performed on nine eccrine
      porocarcinomas and five eccrine poromas. Furthermore, one case of eccrine
      porocarcinoma was analyzed for p16 gene mutation. RESULTS: A striking inverse
      correlation between p16 and RB expression was noted in all of the eccrine
      porocarcinomas and poromas. Strong immunoreactivity for p16 protein was observed
      in both nuclei and cytoplasm of the tumor cells in eight out of nine cases of
      eccrine porocarcinomas, while RB expression was negative in these cases.
      Conversely, one case of eccrine porocarcinoma did not show immunoreactivity for
      p16 protein, whereas RB protein was positive in the scattered nuclei. On the
      other hand, immunostaining of p16 was negative in all cases of five poromas,
      whereas RB-positive nuclei were sparse. No p16 gene mutation was detected in the
      investigated eccrine porocarcinoma case. CONCLUSIONS: These results indicate that
      detectable p16 protein and loss of RB protein are common occurrences in eccrine
      porocarcinoma lesions. Moreover, overexpression of p16 protein may be an
      additional, simple and useful diagnostic marker for eccrine porocarcinoma on
      routine laboratory screening.

PMID- 12207742
TI  - The histologic spectrum of epidermodysplasia verruciformis in transplant and AIDS
      patients.
AB  - BACKGROUND: The purpose of this study was to correlate the histologic findings of
      skin lesions clinically suspicious for epidermodysplasia verruciformis with the
      viral findings in patients with organ transplants or AIDS. METHODS: Thirty-seven
      skin biopsies from 17 patients (six with AIDS and 11 with transplants) were
      studied as a non-randomized, controlled, unblinded case series by in situ
      hybridization for HPV DNA. RESULTS: Nineteen (51%) of these biopsies were HPV
      positive by in situ hybridization either for HPV type 5 (five cases), type 8 (10
      cases), type 16 (four cases) or HPV 31 (one case, with one case of dual
      infection). Only eight of the 19 HPV-positive tissues (42%) showed the classic
      histologic features of verruca planae. The more common histologic feature
      significantly associated with HPV detection was a focally thickened and disrupted
      granular layer (13/19 [68%] vs. 8/18 [44%], p < 0.04). Dysplasia was evident in
      12/19 HPV-positive tissues (63%), which was significantly greater than in
      patients with congenital epidermodysplasia verruciformis (20%). CONCLUSIONS:
      Oncogenic HPV types are detected in about one-half of skin biopsies from
      immunocompromised patients with a clinical presentation suspicious for
      epidermodysplasia verruciformis. Many of these lesions lack the histologic
      features of verruca planae, a focally thickened granular layer is a marker for
      viral detection, and the risk for dysplasia in such lesions is much higher than
      in epidermodysplasia verruciformis not associated with acquired
      immunosuppression.

PMID- 12207744
TI  - CADASIL (cerebral autosomal dominant arteriopathy with subcortical infarcts and
      leukoencephalopathy): a neurovascular disease diagnosed by ultrastructural
      examination of the skin.
AB  - BACKGROUND: CADASIL (cerebral autosomal dominant arteriopathy with subcortical
      infarcts and leukoencephalopathy) is a recently recognized neurovascular disease
      due to mutations of the Notch3 gene, manifesting with strokes or stroke-like
      episodes, major psychiatric symptoms and dementia. The diagnosis can be confirmed
      either by molecular analysis or by ultrastructural examination of the brain or
      more simply the skin. METHODS: The skin of a patient with a suspected diagnosis
      of CADASIL was studied by electron microscopy. RESULTS: Characteristic granular
      osmiophilic material within the basement membrane surrounding pericytes and
      smooth muscle cells of small and medium-sized vessels of the skin were found,
      confirming the diagnosis of CADASIL. CONCLUSIONS: CADASIL is an additional
      example of a neurologic disease that can be diagnosed thanks to electron
      microscopic examination of the skin. Dermatopathologists should be aware of these
      ultrastructural findings, all the more so since the disease could be more common
      than originally thought.

PMID- 12207743
TI  - Melanoma associated with pseudoepitheliomatous hyperplasia: a case series and
      investigation into the role of epidermal growth factor receptor.
AB  - BACKGROUND: Pseudoepitheliomatous hyperplasia (PEH) is a reactive epithelial
      proliferation that occurs in response to underlying infectious, inflammatory, and
      neoplastic conditions. The histologic features of PEH may simulate squamous cell
      carcinoma and may obscure an underlying malignant process. The association of PEH
      with benign melanocytic nevi is well described in the literature. However,
      reports documenting the association of PEH with melanoma are rare. METHODS: We
      examined the demographic and histologic features in 13 cases of melanoma in
      association with PEH. In addition, we evaluated the possible pathogenic role of
      epidermal growth factor receptor (EGFR) using immunohistochemical methods.
      RESULTS: In each case, histologic examination revealed epidermal hyperplasia with
      irregular cords of well-differentiated epithelial cells extending into the dermis
      and infiltrating the melanoma. Although overlap existed, two patterns of
      epidermal hyperplasia were noted. The majority of cases (69%) exhibited
      acanthosis, hyperkeratosis, papillomatosis, and irregular infiltrating epithelial
      cords with squamous eddies. The remaining cases demonstrated basaloid acanthosis,
      laminated orthokeratosis, and horn cysts. EGFR immunohistochemical studies
      revealed strong staining within the basal layer of the epithelium, with no
      discernible difference between the hyperplastic epithelium overlying the melanoma
      cells and adjacent normal skin. Immunostaining among the melanoma cells was
      absent to weak in each of the cases. All cases exhibited intense EGFR
      immunoreactivity in macrophages underlying the epidermal lesions. CONCLUSIONS:
      Melanoma is capable of presenting in a variety of histologic guises, including a
      pattern with PEH. The etiology of PEH, as rarely seen in conjunction with
      melanoma, unlikely involves EGFR and remains to be elucidated.

PMID- 12207745
TI  - CD4+ T lymphocytopenia with disseminated HPV.
AB  - BACKGROUND: There have been several reports of HIV-negative patients with chronic
      idiopathic CD4+ T lymphocytopenia, the diagnostic criteria for which are:
      depressed numbers of circulating T lymphocytes (less than 300/ micro l or less
      than 20%) on more than one occasion; no laboratory evidence of HIV-1 or HIV-2
      infection; and the absence of any defined immunodeficiency or therapy associated
      with depressed levels of CD4+ T lymphocytes. METHODS: We report a patient with
      disseminated human papillomavirus infection associated with idiopathic CD4+ T
      cell lymphocytopenia. A 50-year-old woman presented to the dermatology clinic
      with a 10-year history of widespread verrucae involving the skin and the cervix.
      RESULTS: Biopsy from the arm revealed a common wart. PCR analysis performed from
      the paraffin-embedded block was strongly positive for HPV type 2. Other HPV types
      (including EV-associated HPV 5, 8, 14, 15, 17) were not found. Further laboratory
      work up revealed T-cell lymphocytopenia, with an absolute CD4 count of 21. HIV
      tests were repeatedly negative. She was treated with interferon A 8 million units
      SQ three times per week with partial improvement. The patient underwent a
      hysterectomy for cervical dysplasia and a vulvectomy for vulvar intraepithelial
      neoplasia. She developed small-cell lung carcinoma and died. CONCLUSIONS: The
      diagnosis of idiopathic CD4+ T-cell lymphocytopenia should be considered in any
      patient with widespread viral, fungal, or mycobacterial infection whose HIV test
      is negative, and appropriate evaluation of the absolute CD4+ counts should be
      performed.

PMID- 12207746
TI  - Proliferating trichilemmal tumor with a malignant spindle cell component.
AB  - BACKGROUND: Proliferating trichilemmal tumors (PTTs) are uncommon exuberant
      growths of cells derived from the external root sheath. They tend to occur in
      older women, with a predilection for the scalp. Resection is usually curative.
      Spindle cell components arising within PTTs are exceedingly rare, with only three
      known cases previously reported. Of these three cases, one patient died from
      widespread metastasis. METHODS: Histological and immunohistochemical examinations
      were performed on a tumor from a 54-year-old man which, after exhibiting slow
      growth for 3 years, increased rapidly in size. RESULTS: Microscopic examination
      revealed cystic lobules of squamous cells without a granular cell layer
      surrounding amorphous eosinophilic debris within the dermis. Also present was a
      poorly circumscribed focus of spindle cells with hyperchromasia, pleomorphism,
      giant cells, and abundant mitoses, including abnormal forms. Immunohistochemistry
      showed the spindle cells to stain positively for vimentin, but negatively for
      keratin, epithelial membrane antigen and S-100 antibodies. CONCLUSION: A
      malignant spindle cell component arising within a PTT is a rare neoplasm which
      has been associated with death from widespread metastasis.

PMID- 12207748
TI  - Research governance: for whose benefit?

PMID- 12207749
TI  - In the spirit of creativity: the learning and teaching of ethics in nursing.
AB  - AIM: This paper discusses the development of a pedagogy that nurtures not only
      the caring and the critical, but also the creative spirit of nursing. To explore
      the idea of creative pedagogy the learning/teaching of ethics in nursing is
      considered. BACKGROUND: Based on the understanding of ethics as a deeply personal
      process that is lived in the complexity and ambiguity of everyday nursing work I
      describe a pedagogy that seeks to support students to 'become' moral agents -- to
      see ethics as something they are, not merely as something they follow, and to
      develop the knowledge and ability to live in and navigate their way through the
      complex, ambiguous, and shifting terrain of ethical nursing practice. An example
      of one student's experience is used to illustrate how a pedagogy of creativity
      can promote the development of students' creative capacity in their everyday
      ethical practice.

PMID- 12207750
TI  - Nursing home employment for nursing students: valuable experience or a harsh
      deterrent?
AB  - AIM OF THE STUDY: The primary aim of the study was to examine the attitudes of
      undergraduate nursing students at the both the beginning and end of their nursing
      course. BACKGROUND: Throughout Australia there is increasing awareness of the
      ageing of the population and the widespread implications this will have for the
      future. The ramifications for the health system are expected to be wide and far
      reaching. For the nursing profession the increase in the number of aged people
      will increase the demand for nurses to practice within the aged care area. This
      raises serious concerns in light of the negative attitudes that Registered Nurses
      and undergraduate nursing students hold towards working with older people.
      METHODS: This paper reports the results of a longitudinal study of undergraduate
      nursing students at the start (n = 793) and at the end (n = 524) of their nursing
      education programme. FINDINGS: The findings support the literature in
      demonstrating that working with older people is the least preferred area of
      practice for students, and that its popularity actually declines during the
      education process. One interesting finding from this research suggests that part
      time employment of student nurses in nursing homes can further influence
      students' negative attitudes. CONCLUSIONS: If nursing students are to continue
      working in aged care, strategies to address the potential detrimental impact need
      to be identified and developed as a matter of urgency.

PMID- 12207751
TI  - The lived experience of families of children who are failing to thrive.
AB  - OBJECTIVE: This study was conducted to explore the experience of families of
      children who were failing to thrive. The aim of the study was not to generalize
      the findings but to generate a rich description of the phenomenon of living with
      children who were not growing as expected. BACKGROUND: Although failure to thrive
      has been found to have long-term negative implications for children there is
      little information available on how families experience this phenomenon. METHODS:
      A purposive sample of 12 families with children who were failing to thrive from
      multiple known and unknown reasons were interviewed (21 participants: mothers,
      fathers, and grandmothers). FINDINGS: Twenty-seven subthemes emerged from the
      descriptions provided by the participants and these were then grouped into seven
      themes. Families spoke of an all-encompassing fear with which they lived. They
      were affected by the comparisons of the children made by others and themselves.
      In the process of seeking care for the children, the families described how their
      concerns often were not heard by the professionals. They felt blamed for their
      children's growth failure and this added to a sense of isolation and
      helplessness. Nurses and doctors who listened and acknowledged that they trusted
      the family were respected and valued. Families felt they were then valuable
      members of the care team. Regardless of the difficulties, families described how
      they adapted and persevered in their attempt to provide as normal a life as
      possible for the children. They considered themselves the experts who best knew
      the children and continued to provide the complex care that was needed.
      CONCLUSIONS: The research suggests that health care professionals need to be more
      aware of the impact of their words and actions on families.

PMID- 12207752
TI  - Dis/integrated care: family caregivers and in-hospital respite care.
AB  - AIM: The aim of this study was to explore family caregivers' experiences of in
      hospital respite care for people with dementia and the factors that influenced
      their perceptions of the service. BACKGROUND: The provision of respite care is
      based on the assumption that temporary relief from caregiving will relieve
      caregiver stress and may possibly extend the duration of home care. Research
      evidence suggests that this is a simplistic perspective which fails to account
      for families' concerns about the quality of institutional care and the impact of
      relocation on the person being cared for. DESIGN: Nine family caregivers, using
      four different hospitals sites were interviewed during a period of 3 years from
      1994 to 1997. The research texts were analysed using a critical discourse
      analysis approach drawing on the work of Foucault. FINDINGS: Family caregiver
      texts were distinguished by difference rather than by homogeneity. Caregivers
      occupied a range of positions in terms of their ability to take advantage of the
      respite time intermittent care offered. My reading of these texts has highlighted
      the aspects of nurse-family relationships that ameliorated, or alternately
      exacerbated, the tensions felt by caregivers, as they were torn between the
      necessity to have a break and their anxieties about the impact of in-hospital
      respite care on the person with dementia. CONCLUSION: Nurses' practices in this
      study were a critical element in facilitating, or alternately constraining,
      family caregivers' ability to relinquish care and to take full advantage of the
      respite time. The research findings highlight the need for nurses and other
      formal caregivers to locate themselves in a secondary and supporting caregiving
      role, to acknowledge the family caregivers as the primary caregiver, and use
      family caregivers in-depth and intimate knowledge of the needs of their relative
      to inform care within the institutional setting.

PMID- 12207753
TI  - Discrepancies between patients and professionals in the assessment of patient
      needs: a quantitative study of Norwegian mental health care.
AB  - BACKGROUND: Sensitivity to and respect for the user perspective are important
      facets of user-centred services and empowerment in contemporary mental health
      care. Little is known about the extent to which new policies influence mental
      health work in practice. AIMS: To investigate discrepancy between patients and
      professionals in the assessment of patient needs. Analyses could indicate
      emphasis on user orientation in Norwegian mental health care. METHODS: Patients
      and their respective health professionals (n = 1080) completed separate
      questionnaires regarding patient characteristics and needs. Identifiers were
      removed from the data locally and then entered into a national database.
      Descriptive statistics and multiple regression analysis were used to explore mean
      levels of discrepancy and predictors of discrepancy. RESULTS: Mean discrepancy
      was low, as, on average, 30 of the listed 40 needs were considered absent by both
      the patients and their respective professional. However, the parties showed
      distinct disagreement as to the amount and type of needs that were present.
      Specifically, professionals identified more needs than patients (9.3 vs. 4.3,
      respectively) and this difference was characterized by a strong professional
      emphasis on needs regarding professional monitoring and follow-up. Results showed
      that symptoms of severe cognitive disability were over-represented in the group
      of patients with the highest level of discrepancy, however, the majority of high
      discrepancy patients were not severely disabled on cognitive functions. A
      multiple regression analysis revealed 10 predictors of high discrepancy.
      DISCUSSION: A low professional emphasis on user-orientation may be indicated in
      some cases. Results are discussed with relation to the tension between autonomy
      and beneficence. Suggestions for practice and further research conclude the
      paper.

PMID- 12207754
TI  - 'It's the first scientific evidence': men's experience of pregnancy confirmation.
AB  - BACKGROUND AND AIMS: In contrast to women's experiences of motherhood, there has
      been comparatively little research investigating men's experience of the
      transition to fatherhood and how changing cultural perspectives contribute to the
      contemporary experience of fathering. This paper draws on the findings of a
      larger ethnographic study of men's transition to fatherhood in the United Kingdom
      (UK) and discusses men's experiences of pregnancy confirmation. METHODS: A
      longitudinal ethnographic approach was chosen to investigate men's 'real life'
      accounts of their transition to fatherhood. A mixture of 'novice' and experienced
      fathers (n = 18) were recruited from antenatal classes in the north of the UK
      during 1998. Semi-structured interviews were conducted on three occasions, twice
      during their partner's pregnancy and once afterwards. FINDINGS: Framed by the
      context of the contemporary construction of involved fatherhood, the men
      frequently spoke of their desire to be 'involved' with their partner's pregnancy
      and yet reported difficulty in engaging with its reality. They nevertheless
      participated in a range of activities - body-mediated-moments - which brought
      them closer to their partner's pregnant body and therefore their unborn baby.
      These activities centred on pregnancy confirmation, announcement, foetal
      movements, the ultrasound scan, and culminated in their presence during labour
      and delivery. This paper discusses their involvement in the process of pregnancy
      confirmation. CONCLUSION: The men's experiences of early pregnancy were marked
      forcefully by their involvement in the confirmation process. This activity gave
      men entry into a physical dimension, helping them forge an involvement in the
      pregnancy and shape their early transition to fatherhood. Implications for
      practice. The study has provided insight into expectant men's experiences of
      pregnancy and contributed to the understanding of the changing nature of
      contemporary fatherhood in the UK. Recognition of men's changing roles in
      pregnancy, and greater insight into their experiences should be of relevance to
      all those supporting the transition to parenthood, including midwives,
      obstetricians, ultrasonographers and childbirth educators. Such increased
      awareness should inform the antenatal support given to men and reinforce the
      importance of relevant antenatal preparation that effectively meets the needs of
      not only expectant women, but also expectant men.

PMID- 12207755
TI  - A qualitative study of the experiences of a group of Hong Kong Chinese women
      diagnosed with postnatal depression.
AB  - AIM OF THE STUDY: To examine the lived experiences of a group of Hong Kong
      Chinese women diagnosed with postnatal depression. BACKGROUND: Postnatal
      depression affects approximately 1 in 10 childbearing women in Hong Kong.
      However, most studies of postnatal depression have been carried out in Western
      societies and no qualitative research was found describing the experience of Hong
      Kong Chinese mothers with postnatal depression. DESIGN: A phenomenological study
      was conducted. Data were collected by semi-structured interviews. A purposive
      sample of 35 women diagnosed with postnatal depression was interviewed. Interview
      data were analysed following Colaizzi's phenomenological methodology. RESULTS:
      Themes that emerged describing participants' experiences included trapped in the
      situation, ambivalent towards the baby, uncaring husband, and controlling and
      powerful in-laws. Women felt hopelessness, helplessness and loss of control. They
      were trapped in a situation that had no way of escape except by violent means,
      such as homicide or suicide. Feelings towards the baby were ambivalent, both hate
      and love. Several women had injured, or had thought of injuring or killing, their
      babies and/or themselves. Women's unhappiness was attributed to a noncaring
      husband, and controlling and powerful in-laws. Generally, women did not seek help
      until their depression was diagnosed by screening tests. CONCLUSION: This study
      has revealed insights into how women experienced postnatal depression in Hong
      Kong, and what they perceived as contributing to their depression. These insights
      may be used to guide interventions for women and their families to raise
      awareness regarding the support childbearing women need.

PMID- 12207756
TI  - Relieving discomforts: the help-seeking experiences of Chinese perimenopausal
      women in Taiwan.
AB  - BACKGROUND: Although studies show that women view perimenopause as a natural
      process, few studies explore the experiences of Taiwanese mid-life women who
      visit clinics for perimenopausal health problems. Research is required to
      understand the patterns and explanations for the women's behaviours in the
      process of seeking medical help. Such understanding will help guide teaching and
      care-giving approaches. AIMS: To generate a descriptive theoretical framework
      about the experiences of women who visited traditional Chinese and Western
      medicine clinics in Taiwan to seek medical help for perimenopausal symptoms.
      METHODS: A grounded theory research design was used. Thirty Taiwanese women, aged
      48-55 years, participated in two face-to-face audio-taped interviews. Trained
      staff nurses conducted the interviews. Data collection, coding of interviews and
      field notes, and data analysis occurred simultaneously. FINDINGS: Relieving the
      discomforts' was the core theme for describing and guiding the process of seeking
      medical help during the perimenopausal period. During the process, 'Feeling the
      discomforts' was identified as the antecedent condition. Analyses showed five
      dimensions to the women's help-seeking behaviours: (1) searching for medical
      help, (2) taking medicine, (3) reassurance of health, (4) desiring to be
      understood, and (5) emotional swings. CONCLUSIONS: Women in this study expected
      to relieve their perimenopausal discomforts by finding treatment to match their
      body constitution. They hoped to find a caring and understanding doctor or staff
      member who would carefully explain health-related issues to them. Health care
      providers need to consider women's individual health values and, based on these
      values, use different approaches to treat and teach women with perimenopausal
      symptoms and concerns.

PMID- 12207757
TI  - Preparing for change in the secondary prevention of coronary heart disease: a
      qualitative evaluation of cardiac rehabilitation within a region of Scotland.
AB  - BACKGROUND: Secondary prevention of Coronary Heart Disease (CHD) is often poorly
      managed and its benefits attained in only a minority of those with CHD.
      Guidelines developed in the United Kingdom and North America suggest that in
      future cardiac rehabilitation programmes should provide services through
      individualized programmes that cater for a wide range of conditions associated
      with CHD. This will involve substantial and costly changes to current programmes
      that are mostly standardized and for postmyocardial infarction patients. Based on
      change theory, this study examined the dynamics, strengths and weaknesses of an
      existing programme in a Scottish region which was due to undergo the changes
      suggested by guidelines. AIM: To examine the perceived provision of secondary
      prevention services for CHD from the perspectives of health professionals within
      one region in the West of Scotland. METHODS: A purposive sample of 14 health
      professionals (eight primary and six secondary care health professionals) was
      selected to cover a range of professional roles including both specialists and
      generalists. Separate focus group discussions (2) were held with primary care and
      secondary care professionals. FINDINGS: Whilst the health professionals were
      enthusiastic about CHD prevention and their involvement, they perceived barriers
      to the success of the existing service as being complex and multifactorial,
      including patient, social and service-related factors. Although both groups
      identified motivation as the most influential personal factor, secondary care
      staff tended to focus on the importance of patient factors in influencing
      motivation to change, whereas the primary care staff referred more to the
      cumulative effects of social and cultural factors. Professionals highlighted
      weaknesses in the transition between hospital and community-based services with
      regard to the information flow between primary and secondary care. CONCLUSIONS:
      Although the study has immediate relevance for the local area, it highlighted
      issues of more general relevance to cardiac rehabilitation programme development
      and intersectoral working, such as communications and role perceptions in multi
      professional working and the need to adapt services to local socio-economic
      conditions.

PMID- 12207758
TI  - Comfort: exploration of the concept in nursing.
AB  - BACKGROUND: Comfort is a substantive need throughout life. However, the rise of
      technological influence coupled with a desire to embrace the medical concept of
      cure has frequently relegated the importance of nursing comfort interventions to
      simple tasks that can be provided by non-professional caregivers rather than an
      integral part of health promotion at all levels. DEFINITION: Comfort is a concept
      that has been explored by a number of authors. Various definitions have included
      comfort as an outcome of nursing, a function of nursing, a basic human need, and
      a process. No consensus on a definition of comfort was found in the literature.
      THEORY: This investigation attempts to link the ideas of comfort presented in the
      literature with the theories of Watson (Human Care) and Leininger (Culture Care),
      and discovers the existence of an integral locus for comfort in both.
      IMPLICATIONS: Theory-based strategies for nursing education are offered. Further
      research is clearly required, research methodologies based on Watson and
      Leininger would be appropriate for additional exploration of this concept.
      Practice implications include reflecting on the meaning of comfort to the patient
      in the context of his/her cultural values, and using this one as one of the
      factors in planning and implementing nursing care. CONCLUSION: Given the current
      emphasis on health promotion and the importance of comfort to the process of
      healing, comfort is an indispensable element of holistic, culturally congruent
      human care.

PMID- 12207759
TI  - Skin manifestations of Bartonella infections.

PMID- 12207760
TI  - Localized scleroderma/morphea.

PMID- 12207761
TI  - Pellagra and skin.

PMID- 12207762
TI  - Rapid initiation of repigmentation in vitiligo with Dead Sea climatotherapy in
      combination with pseudocatalase (PC-KUS).
AB  - BACKGROUND: Low catalase levels and cellular vacuolation in the epidermis of
      patients with vitiligo support major oxidative stress in this compartment. There
      is now in vivo evidence for increased epidermal hydrogen peroxide (H(2)O(2))
      accumulation in this patient group by utilizing noninvasive Fourier Transform
      Raman spectroscopy (FT Raman). Epidermal H(2)O(2) can be removed with a topical
      application of narrow band UVB activated pseudocatalase cream (PC-KUS). (Mn/EDTA
      bicarbonate complex, patent No. EPO 58471 1 A), yielding initiation of
      repigmentation. Dead Sea climatotherapy is another successful treatment modality
      for vitiligo, but the mode of action has escaped definition so far. METHODS:
      Epidermal hydrogen peroxide (H(2)O(2)) was assessed in vivo before and after 21
      days treatment at the Dead Sea using noninvasive Fourier-Transform Raman
      spectroscopy. The effectiveness of repigmentation was followed in 59 patients
      with vitiligo by comparing Dead Sea climatotherapy alone with the combination of
      Dead Sea climatotherapy/pseudocatalase cream (PC-KUS) as well as Dead Sea
      climatotherapy/placebo cream. Clinical repigmentation was documented by
      standardized black/white photography using non-UV coated bulbs as flashlight and
      by color photography. RESULTS: This study on 59 patients who had vitiligo for an
      average time of 17 years (range 3-53 years) confirmed in vivo H(2)O(2)
      accumulation in mM concentrations in the epidermis of untreated patients.
      Furthermore, we demonstrated a pseudocatalase activity after 15 min of Dead Sea
      bathing, but the decrease of epidermal H(2)O(2) levels was significantly less
      compared to narrowband UVB activated pseudocatalase cream (PC-KUS). Initiation of
      repigmentation was already observed between day 10 and day 16 after a combination
      of Dead Sea climatotherapy/pseudocatalase cream compared to conventional
      pseudocatalase monotherapy (8-14 weeks) and Dead Sea climatotherapy alone (5-6
      weeks). CONCLUSION: The results of this study show a significantly faster
      initiation of repigmentation in vitiligo after a combination of short-term
      climatotherapy (21 days) at the Dead Sea in combination with a pseudocatalase
      cream (PC-KUS) compared to either conventional climatotherapy at the Dead Sea
      alone or with placebo cream in combination with climatotherapy. This combined
      therapy is significantly faster in repigmentation than narrowband UVB activated
      pseudocatalase cream (PC-KUS) treatment alone. The results of this study support
      the necessity of epidermal H2O2 removal as well as the influence of solar UV
      light in the successful treatment of vitiligo.

PMID- 12207763
TI  - Lupus erythematosus panniculitis: a clinicopathologic study.
AB  - BACKGROUND: Lupus erythematosus panniculitis is a clinical variant of lupus
      erythematosus which involves the deep dermis and the subcutaneous fat. The
      purpose of this study was to ascertain the clinical profile of Asian patients
      with this condition. METHODS: This was a retrospective study of all
      histologically confirmed lupus panniculitis seen at our center between 1992 and
      1997. The age, sex, past history/subsequent diagnosis of systemic lupus
      erythematosus (SLE), presence of clinical discoid lupus erythematosus (DLE)
      changes on overlying skin, direct immunofluorescence, serologic, and histologic
      findings were analyzed. RESULTS: There were 12 cases of lupus panniculitis, two
      of which were in patients already diagnosed with SLE and one in which the patient
      subsequently evolved into SLE. The mean age at diagnosis was 31.3 years. The face
      (50%), upper limbs (33%), and scalp (25%) were the most common sites of
      involvement. Thirty-three per cent had clinical evidence of DLE on the overlying
      skin, whilst 67% had histologic features of DLE on the overlying skin. A lupus
      band was present in 36%. Antinuclear antibody (ANA) was positive in three of 11
      cases; these were in the two patients who already had SLE and in the only patient
      who progressed to SLE. All of the cases showed fat necrosis and, in the majority
      of cases, there was associated lobular and paraseptal inflammation. Thirty-three
      per cent showed lymphocytic vasculitis and 75% had mucin deposition. None had
      lymphoid nodules, subepidermal hyalinization, or calcification. CONCLUSIONS:
      Lupus panniculitis affects a younger age group in Asians as compared with the
      Western population. Although about one-third of patients show clinical evidence
      of overlying DLE, two-thirds of patients show histologic evidence of DLE. It
      tends to have a mild disease course in the majority of cases.

PMID- 12207764
TI  - Perianal actinomycetoma experience of 20 cases.
AB  - BACKGROUND: Actinomycetoma is a chronic infection resulting from aerobic
      Actinomycetes. The major agents are Nocardia brasiliensis, Actinomadura madurae,
      and Streptomyces somaliensis. The most frequent topographies are the lower and
      upper limbs. The prognosis of this disease is determined by several factors, such
      as etiologic agent, clinical topography, and depth of disease (degree of
      involvement, visceral, and bone affection). The purpose of this paper was to
      present our experience with actinomycetoma of the perianal region. METHODS: This
      study comprises 20 cases of perianal actinomycetoma, all of which were clinically
      and microbiologically proven by direct examinations, cultures, and biopsies.
      Clinical responses to the two principal treatment regimes used [combination of
      trimethoprim-sulfamethoxazole (TMS/SMX) and diaminodiphenylsulfone (DDS) or
      amikacine plus TMS/SMX] are reported. RESULTS: Most of the cases were male
      (17/20, 85%), the mean age was 42.1 years, and the farmers predominated (90%).
      The principal etiologic agent isolated was N. brasiliensis (85%). CONCLUSIONS:
      Perianal actinomycetoma is a rare entity. Differential diagnosis with anal
      sinuses, hydroadenitis, and cutaneous tuberculosis must be made in endemic areas
      by performing mycologic tests and biopsies. Treatment depends on the etiologic
      agent involved and the patient's condition.

PMID- 12207765
TI  - Correlation between pH and irritant effect of cleansers marketed for dry skin.
AB  - BACKGROUND: Although it is important that dermatologists and the general
      population know the irritation potential of products marketed for dry skin used
      for body cleansing, this information is not usually available. OBJECTIVE: To
      assess the irritative effect of different soaps and liquid cleansers recommended
      for sensitive skin. To study the correlation of the irritation effect of each
      substance with its pH and with the presence or absence of syndet in the product.
      METHODS: Seventeen products marketed for dry skin and 12 common soaps used by the
      general population were studied. Fresh soap emulsions (8%) were applied to the
      volar side of the right forearm of 30 individuals with sensitive skin for 5
      consecutive days using aluminum chambers. The appearance of irritation (erythema,
      scaling and fissures) was recorded, scored, and expressed in an Irritation index
      (IrIn). The pH of each solution was measured. RESULTS: Products with a low IrIn
      were White Dove (Dove, Lever Pond's, Toronto, Ontario, Canada), Dove Baby,
      Cetaphil (bar) (Cetaphil, Gulderma Lab., Forth Worth, TX, USA), Dove liquid
      cleanser for hands, Dove pink, and Aderma (Adenma, Pierre Fabre, Dermo
      Cosmetique, Boulagne, France). Most corresponded to syndet products. Among the
      most used brand-name soap, Camay Classic (Camay, Procter & Gamble de Mexico,
      Mexico, U.F.) had the lowest IrIn. Dove Baby was the only product with a neutral
      pH. A significant correlation between pH and the IrIn of cleansers was found (P <
      0.006). CONCLUSIONS: Most products recommended for sensitive skin have a
      considerable irritation effect, which is related to the pH of the product. Better
      regulation of advertisement specifications including the pH level and type of
      cleanser contained is necessary for the majority of soaps and cleansers.

PMID- 12207766
TI  - Epidermodysplasia verruciformis: 14 members of a pedigree with an intriguing
      squamous cell carcinoma transformation.
AB  - A 38-year-old farmer was apparently well until 5 years of age. At this age, the
      patient's mother found mildly itchy, raised eruptions over the scalp during
      combing of the scalp hair. Since then, the eruptions have progressed insidiously
      to involve the face and other parts of the body, with a preponderance over the
      face, upper back, and chest, including the palms. The soles, oral cavity, and
      genital tract were unaffected. The lesions were persistent in nature and showed
      no remission or exacerbation. Mild to moderate pruritus/discomfort was
      experienced following sunlight exposure. A prominent, raised eruption appeared on
      the right side of the forehead 9 years ago, 25 years after the initial eruptions,
      which in due course ulcerated. It was progressive in nature and acquired a large
      size. Two years later, it was diagnosed as squamous cell carcinoma, for which
      liquid nitrogen cryosurgery was performed. There was a recurrence of the lesion
      at the site of surgery, which was excised 4 months later. Subsequently, there was
      a sudden flare up at the same site. It was badly infected with maggot
      infestation. The relentless course of the disease was evident by the appearance
      of two similar lesions, one on the right half of the nose and the other on the
      left preauricular region. A short while ago, fatigue and loss of weight were also
      recorded. Bladder and bowel functions were normal and there was no loss of
      appetite, hoarseness of voice, or breathlessness. Four of the patient's six
      children (three sons and one daughter) were reported to have similar lesions all
      over the body. In addition, nine other relatives were also affected. Accordingly,
      a total of 14 (12 males and two females) family members were found to be affected
      from amongst 41 individuals (26 males and 15 females) spread across several
      generations (Fig. 1). There was a second-degree consanguinity of marriage, with
      the patient's grandmother and wife's father being brother and sister. Skin
      surface examination was marked by multiple, discrete, flat-topped, scaly,
      brownish-black papules of diverse morphology, from hypopigmented macules to
      verrucous lesions, with a few coalescing to form plaques. The scales were brown,
      dry, and adherent (Fig. 2a). The lesions were conspicuous by their presence over
      the face, neck, and front and back of the chest. The extremities were also
      affected. Nevertheless, the soles and genitalia were spared. The oral mucosae,
      hair, and nails were normal. Koebner's phenomenon was explicit, whereas Auspitz's
      sign was not demonstrable. In addition, a perceptible nodulo-ulcerative lesion
      (size, 3 in x 2 in) with indurated, raised, averted margins was encountered on
      the right side of the forehead. The ulcer was tender and had a fetid discharge.
      Necrotic slough was prominent over its base. Similar lesions were located on the
      left preauricular region and right half of the nose. Hematoxylin and eosin
      stained sections prepared from biopsies taken from representative lesions of
      epidermodysplasia verruciformis and squamous cell carcinoma revealed their
      diagnostic features. Epidermodysplasia verruciformis showed features of
      hyperkeratosis and acanthosis with hardly any papillomatosis. Marginal elongation
      of the rete ridges was present. Extensive vacuolization was a remarkable feature,
      and was largely confined to the upper stratum Malpighian and the granular cell
      layer. Some of the vacuolated cells were fairly large; their nuclei were located
      in the center and had variable pyknosis. The granular cell layer was uniformly
      thickened, whereas the stratum corneum had a loosely felted (basket-weave)
      appearance. The dermis was apparently normal (Fig. 2b,c). The other
      microsection(s) from squamous cell carcinoma were conspicuous by the presence of
      hyperkeratosis, acanthosis, and irregular masses of epidermal cells,
      proliferating downwards and invading the dermis. Varying proportions of
      differentiated squamous cells formed their bulk. These cells were atypical,
      characterized by variations in size and shape, hyperplasia and hyperchromasia of
      the nuclei, absence of prickles, chas, characterization of individual cells, and
      the presence of both mitotic and atypical mitotic figures (Fig. 3b).

PMID- 12207767
TI  - En coup de sabre.
AB  - A man born in 1961 was apparently well until his marriage in May 1986. In August
      of that year, his attention was drawn to the presence of a reddish patch over the
      right forehead. It was initially asymptomatic. It continued to progress to form
      an apparent linear furrow extending from the receding hairline to the vertex and
      temporal part of the scalp. At this juncture, the patient experienced moderate
      pain when laughing. Five years later the patient experienced a constant boring
      pain affecting the right eyeball. Consultation with an ophthalmologist led to
      sacrificial enucleation of the right eye despite the lack of a precise diagnosis.
      Nevertheless, the initial condition continued to progress causing disfigurement
      of the right side of the face. Examination of the face was marked by perceptible
      asymmetry. A linear atrophic plaque in the form of a furrow was identified on the
      right side of the forehead extending from the eyebrow to the vertex and temporal
      part of the scalp. The skin over the furrow was taut and bound down (Fig. 1). A
      hematoxylin and eosin-stained section prepared from the lesion revealed marked
      thickening of the dermis. The collagen bundles were hypertrophied and closely
      packed together. The staining was homogeneously eosinophilic. It was largely
      devoid of inflammatory infiltrate. The changes in the blood vessels were
      conspicuous by narrowing of the lumina, thickening of the walls, and a sparse
      perivascular lymphocytic infiltrate. Pilosebaceous units were completely absent,
      whereas a few atrophic pulled-up sweat glands were located in the mid-dermis.
      Similar changes were observed in the subcutaneous tissue. The epidermis was
      largely atrophied, with flattening of the rete ridges.

PMID- 12207768
TI  - Leishmaniasis recidiva cutis: an unusual two steps recurrence.

PMID- 12207769
TI  - An interesting case of colocalization of segmental lichen planus and vitiligo in
      a 14-year-old boy.

PMID- 12207770
TI  - Dissecting cellulitis in a white male: response to isotretinoin.

PMID- 12207771
TI  - Leukomelanodermic leprosy.

PMID- 12207772
TI  - Erythema annulare centrifugum and pregnancy.

PMID- 12207773
TI  - Reticulate acropigmentation of Kitamura-Dowling Degos disease overlap: a case
      report.

PMID- 12207775
TI  - Reply to commentary by Drs Majewski & Jablonska, "Human papillomavirus and
      oncogenesis: critical evaluation of recent findings".

PMID- 12207774
TI  - Evaluating the efficacy of allopurinol and meglumine antimoniate (Glucantime) in
      the treatment of cutaneous leishmaniasis.
AB  - BACKGROUND: Cutaneous leishmaniasis is a common disease in Iran, particularly in
      Kerman province. It usually occurs via the bite of an infected sandfly. METHODS:
      One hundred and fifty patients suffering from cutaneous leishmaniasis were
      included in this study in Kerman. The patients were randomly divided into three
      groups. They were matched with regard to age, sex, duration of the disease, and
      type, number, and site of the lesions. For each group, one of the following
      therapeutic methods was applied: (i) oral allopurinol (15 mg/kg/day) for 3 weeks;
      (ii) intramuscular injection of Glucantime (30 mg/kg/day), corresponding to 8
      mg/kg/day of pentavalent antimony, for 2 weeks; (iii) combined therapy. The
      lesions were re-examined at the end of treatment and 2 and 4 weeks later. The
      response to treatment was graded as excellent (reduction in the size of the
      lesion by at least 80% or complete clearance), good (reduction in the size of the
      lesion by 50%), and poor (minimal or no change in the lesion). RESULTS: The
      overall results indicated that 18% of patients showed excellent response, 6% good
      response, and 76% poor response in the first group. In the second group, 24% of
      patients showed excellent response, 6% good response, and 70% poor response. In
      the third group, 46% of patients showed excellent response, 8% good response, and
      46% poor response. CONCLUSIONS: The results obtained by the three therapeutic
      methods indicated that combined therapy with allopurinol plus Glucantime was much
      more effective than that obtained by each of the two drugs when used alone (P <
      0.05).

PMID- 12207776
TI  - Transition of pemphigus vulgaris into pemphigus foliaceus confirmed by
      antidesmoglein ELISA profile.

PMID- 12207777
TI  - Digital angioleiomyoma.

PMID- 12207778
TI  - Recurrent herpes zoster revisited.

PMID- 12207779
TI  - Pemphigus and smoking.

PMID- 12207780
TI  - Minocycline hypersensitivity syndrome manifesting with rhabdomyolysis.

PMID- 12207781
TI  - Endocervical adenocarcinoma and its variants: their morphology and differential
      diagnosis.
AB  - Adenocarcinoma of the uterine cervix and its variants account for a much greater
      number of cases in routine practice of histopathology than they did several
      decades ago. The varied morphology of these tumours results in diverse problems
      in differential diagnosis. The overall area of glandular pathology of the cervix,
      of which invasive adenocarcinoma is only one subset, is further complicated by
      the fact that there are many benign glandular proliferations of the cervix that
      can potentially be misinterpreted as adenocarcinoma. In this review the
      histopathology of endocervical adenocarcinoma and its variants is presented with
      the emphasis on evaluation of routinely stained sections, still the bedrock of
      routine practice, relatively little aid being provided by immunohistochemistry or
      other new techniques, contrary to what is sometimes implied in the literature.
      Description of the appearance of each subtype of adenocarcinoma or variant
      thereof is followed by a section on their differential diagnosis. Eighty percent
      of endocervical carcinomas are of the so-called usual type being characterized by
      cells with eosinophilic cytoplasm and generally brisk mitotic activity. It is
      sometimes stated that endocervical adenocarcinomas are mucinous but the usual
      form just noted often has little or no mucin. Pure or almost pure mucinous
      adenocarcinoma do occur, however, and have an important subtype, the so-called
      adenoma malignum (minimal deviation adenocarcinoma). Although treacherous because
      of its bland cytological features and sometimes deceptive pattern, a cone biopsy
      or hysterectomy specimen showing this neoplasm typically has easily recognizable
      features that indicate the presence of an infiltrative adenocarcinoma. An
      important variant of usual endocervical adenocarcinoma is the well differentiated
      villoglandular papillary adenocarcinoma, a designation that should be reserved
      for tumours with grade 1 cytologic features as usual endocervical adenocarcinoma,
      which is typically grade 2, may have papillae. In our opinion all other variants
      of pure adenocarcinoma, including endometrioid, are rare and include in addition
      to the latter clear cell, serous and mesonephric neoplasms. Tumours with a
      glandular and nonglandular component are also reviewed: adenosquamous carcinoma,
      glassy cell carcinoma, adenoid basal carcinoma, 'adenoid cystic' carcinoma and
      adenocarcinoma admixed with a neuroendocrine tumour.

PMID- 12207782
TI  - Malignant neoplasms infiltrating pseudoangiomatous' stromal hyperplasia of the
      breast: an unrecognized pathway of tumour spread.
AB  - AIMS: To describe five malignant tumours in the breast (two invasive carcinomas
      and three non-Hodgkin's lymphomas) showing an unusual pattern of spread within
      anastomosing spaces consistent with those described in pseudoangiomatous stromal
      hyperplasia. METHODS AND RESULTS: The histological and immunohistochemical
      features of the cases are presented. In all cases, the neoplasms consisted of non
      cohesive E-cadherin-negative cells located within anastomosing vascular-like
      channels. These channels showed morphological and immunohistochemical features
      consistent with those seen in pseudoangiomatous stromal hyperplasia: they were
      lined by flattened cells that expressed CD34, bcl2 and smooth muscle actin, while
      CD31 was consistently negative. CONCLUSIONS: The open channels of
      pseudoangiomatous stromal hyperplasia have been regarded as spaces due to loss of
      cohesiveness between stromal fibroblasts if not artefacts. The fact that
      neoplastic cells spread through these spaces suggests that the spaces are true
      open channels that may represent part of a complex network of stromal channels
      (pre-lymphatics) connected to the main lymphatic system of the breast. This
      finding opens new insights into the routes of tumour spread.

PMID- 12207783
TI  - T-cell/histiocyte-rich large B-cell lymphoma is a disseminated aggressive
      neoplasm: differential diagnosis from Hodgkin's lymphoma.
AB  - AIMS: An accurate diagnosis of T-cell/histiocyte-rich large B-cell lymphoma needs
      to take into consideration those forms of Hodgkin's lymphoma also characterized
      by a predominance of small lymphocytes and histiocytes, i.e. nodular lymphocyte
      predominance Hodgkin's lymphoma and lymphocyte-rich classical Hodgkin's lymphoma.
      We have studied the clinical, phenotypic and genetic features of a series of 12
      cases of T-cell/histiocyte-rich large B-cell lymphoma along with 18 cases of
      Hodgkin's lymphoma for comparative purposes. METHODS AND RESULTS: Of the
      Hodgkin's lymphoma cases, there were 11 lymphocyte predominance type and seven
      classic type. T-cell/histiocyte-rich large B-cell lymphomas presented usually in
      advanced stages (III or IV in 11/12 cases), frequently with 'B' symptoms (6/9
      cases), and followed a more aggressive course than Hodgkin's lymphoma (4/8
      patients died due to the tumour in T-cell/histiocyte-rich large B-cell lymphoma
      versus 0/15 in Hodgkin's lymphoma). T-cell/histiocyte-rich large B-cell lymphoma
      cases showed diffuse effacement of the nodal architecture by a proliferation of
      scattered large atypical B-cells obscured by a background of small T-lymphocytes
      (more CD8+, TIA1+ than CD57+). Five cases showed also a prominent histiocytic
      component. The large B-cells expressed CD45 and often EMA (6/10 cases). On the
      other hand, CD 30, CD15 and latent infection by Epstein-Barr virus (EBV) were
      generally lacking. bc l6 and CD10 were, respectively, detected in 6/6 and 1/5
      cases. Conventional polymerase chain reaction (PCR) showed monoclonal
      immunoglobulin heavy chain (IgH) gene rearrangements in all T-cell/histiocyte
      rich large B-cell lymphomas studied (5/5), but did not detect any case with
      t(14;18) involving the major breakpoint region (0/4). CONCLUSIONS: The
      differential diagnosis of T-cell/histiocyte-rich large B-cell lymphoma from
      Hodgkin's lymphoma is facilitated by the integration of different
      immunophenotypic, molecular and clinical findings. T-cell/histiocyte-rich large B
      cell lymphoma is a monoclonal neoplasm of bc l6+ B-cells with a phenotypic
      profile similar to lymphocyte predominance Hodgkin's lymphoma, suggesting a
      germinal centre origin and a possible relation to this disease. Therefore, in
      order to distinguish it from lymphocyte predominance Hodgkin's lymphoma,
      characterization of the reactive background, IgH gene rearrangement studies by
      conventional PCR and clinical features are more useful. In contrast, T
      cell/histiocyte-rich large B-cell lymphoma can be distinguished from classical
      Hodgkin's lymphoma thanks to the presence of monoclonal IgH rearrangement and the
      CD 30-CD15-CD45+EMA+ immunophenotypic profile of the neoplastic cells in T
      cell/histiocyte-rich large B-cell lymphoma.

PMID- 12207784
TI  - CD34+ stromal cells and hyalinized vascular changes in the anal fibroepithelial
      polyps.
AB  - AIMS: To elucidate the pathogenesis of the anal fibroepithelial polyp, we
      examined surgically resected lesions histopathologically. METHODS AND RESULTS:
      Twenty-seven surgically resected anal fibroepithelial polyps were investigated
      histologically with an additional immunohistochemical examination using anti
      CD34. For a control study, the surgical specimens of the anal canal showing non
      polypoid lesions, obtained from haemorrhoidectomy (18 specimens) and rectectomy
      (five specimens) due to rectal cancer without anal canal involvement, were also
      analysed. We demonstrated characteristic spindle or stellate cells
      immunohistochemically positive for CD34 in the anal fibroepithelial polyps
      (24/27, 89%). The number of CD34+ cells was statistically related to the size of
      anal fibroepithelial polyps, although CD34+ stromal cells were recognized in the
      non-polypoid anal submucosa and haemorrhoids. We also found hyalinized vascular
      changes in the base of six anal fibroepithelial polyps examined. These features
      were not detected in the non-polypoid anal canal. CONCLUSIONS: An increase in
      CD34+ stromal cells may play a role in the enlargement of anal fibroepithelial
      polyps. CD34+ stromal cells are suggested to be distinctive mesenchymal cells
      with a capability for tissue repair and overgrowth. The vascular impairment could
      be secondary change associated with localized tissue damage by abnormal traction.

PMID- 12207785
TI  - Cytokeratin 19 and galectin-3 immunohistochemistry in the differential diagnosis
      of solitary thyroid nodules.
AB  - AIMS: The immunohistochemical expression of cytokeratin 19 (CK 19) and galectin-3
      was evaluated in 69 thyroid lesions to assess their potential as markers in the
      diagnosis and classification of thyroid malignancy. The following were studied:
      26 cases of papillary carcinoma, 12 of follicular carcinoma, 20 follicular
      adenomas, two medullary carcinomas, one anaplastic carcinoma and eight
      multinodular goitres. METHODS AND RESULTS: Formalin-fixed paraffin-embedded
      thyroid tissues were stained immunohistochemically for both CK 19 and galectin-3.
      CK 19 expression was found in all 26 papillary carcinomas, five of 12 follicular
      carcinomas, two of two medullary carcinomas and one case of anaplastic carcinoma.
      Only five of 20 follicular adenomas were positive for CK 19, and this was in a
      focal distribution. Two of eight multinodular goitres stained focally positive.
      Galectin-3 expression was found in 22 of 26 papillary carcinomas, 12 of 12
      follicular carcinomas and one of two cases of medullary carcinoma. Only two of 20
      follicular adenomas were positive. Three of eight multinodular goitres showed
      focal galectin-3 expression. CONCLUSIONS: Our findings suggest that the
      immunohistochemical localization of CK 19 and of galectin-3 is a useful adjunct
      to the histopathological diagnosis of a solitary thyroid lesion. The expression
      of CK 19 favours a diagnosis of papillary carcinoma in all its variant patterns.
      Galectin-3 may serve as a marker for the recognition of follicular carcinoma,
      particularly the minimally invasive form.

PMID- 12207786
TI  - Salivary duct carcinoma: cytokeratin 14 as a marker of in-situ intraductal
      growth.
AB  - AIMS: The aim of this study was to determine the immunoprofile of salivary duct
      carcinoma and to differentiate intraductal growth from invasive growth. METHODS
      AND RESULTS: We applied a panel of antibodies (cytokeratins 7, 8, 13, 14, 19,
      vimentin and alpha-smooth muscle actin) in five cases of salivary duct carcinoma.
      This panel is currently used for identification of different components of
      salivary gland tumours in our laboratory. All tumour cells were positive for
      cytokeratins 7 and 8. Few neoplastic structures expressed cytokeratin 14 in cells
      surrounding tumour islands. CONCLUSION: The finding of cytokeratin 14 was
      important to confirm the in-situ intraductal growth, which probably characterizes
      this low-grade neoplasm.

PMID- 12207787
TI  - Polymorphous low-grade adenocarcinoma of the salivary glands with transformation
      to high-grade carcinoma.
AB  - AIMS: Polymorphous low-grade adenocarcinoma of the minor salivary glands is an
      infiltrative neoplasm characterized by bland-looking tumour cells arranged in
      diverse architectural patterns. It is considered to be of low-grade malignant
      potential in that nodal metastases are seen in only a minority, and distant
      spread is rare. Even more unusual is the transformation of polymorphous low-grade
      adenocarcinoma to a histologically high-grade carcinoma, i.e. dedifferentiation.
      In this paper, we describe the clinicopathological and immunohistochemical
      findings in two further examples. METHODS AND RESULTS: Two patients presented
      each with a tumour of the palate. Histopathological examination showed the
      typical morphological, cytological and immunohistochemical features of a
      polymorphous low-grade adenocarcinoma. In one case there was a second component
      of high-grade carcinoma showing nuclear atypia, markedly increased mitotic
      activity and MIB1 index, as well as prominent zones of necrosis. It expressed
      epithelial markers and androgen receptors, and thus resembled salivary duct
      carcinoma. Similar tumour tissue was observed in one of the cervical nodal
      metastases, which was biopsied at the same time as the palate. In the second
      patient, a high-grade component was discovered when the tumour recurred in the
      palate 13 years after the initial biopsy. Whilst morphologically similar to that
      in first case, there were significant immunohistochemical differences such as
      retention of some of the polymorphous low-grade adenocarcinoma profile and
      absence of androgen receptor expression. CONCLUSIONS: Polymorphous low-grade
      adenocarcinoma was first described relatively recently, and as experience with it
      continues to accumulate, it is becoming clear that late recurrences and
      metastases, whilst still infrequent, may not be quite as rare as previously
      thought. Reports of histological transformation are even scarcer, and most
      occurred at least 13 years after the polymorphous low-grade adenocarcinoma was
      initially recognized. It is a real possibility that this phenomenon, like
      clinical progression, may also be encountered more often as time passes.
      Therefore, we believe that, whilst polymorphous low-grade adenocarcinoma is
      certainly far less aggressive than, for example, adenoid cystic carcinoma, it
      nevertheless remains a true malignancy with a potential to prove fatal in a
      minority of patients.

PMID- 12207788
TI  - Malignant mesothelioma: PAS-diastase positivity and inversion of polarity in
      intravascular tumour.
AB  - AIMS: Periodic acid-Schiff (PAS)-diastase-positive material was identified within
      pseudoglandular structures within the small intravascular component of two
      pleural malignant mesotheliomas. The aim of this study was to ascertain the
      nature of this material and to asses the polarity of the cells forming the
      pseudoglandular structure. METHODS AND RESULTS: Immunohistochemistry was
      performed using antibodies to laminin and type IV collagen and the antibody HBME
      1. These demonstrated the material to be basement membrane rather than mucin. The
      apical polarity marker HBME-1 was not related to the internal pseudoglandular
      structure but stained the periphery of intravascular tumour clumps. CONCLUSIONS:
      Pseudoluminal PAS-diastase-positive material in malignant mesothelioma may easily
      be mistaken for epithelial mucin, leading to an erroneous diagnosis of
      adenocarcinoma. The presence of basement membrane material in pseudolumina, as
      defined by the presence of laminin and type IV collagen, surrounded by tumour
      cells whose external surface expresses the apical polarity marker HBME-1 implies
      inversion of polarity of tumour cells within vascular spaces.

PMID- 12207789
TI  - Respiratory failure due to micronodular type II pneumocyte hyperplasia.
AB  - AIMS: To report the first case of respiratory failure due to micronodular type II
      pneumocyte hyperplasia. METHODS AND RESULTS: Biopsy, explant and autopsy material
      from a 16-year-old girl, a smoker, with no personal or family history of tuberous
      sclerosis, who died following lung transplantation necessitated by progressive
      respiratory failure, was evaluated histologically. Micronodular pneumocyte
      hyperplasia was identified histologically as the cause of the respiratory
      failure. Foci of hyperplastic type II pneumocytes measuring up to 4 mm were
      widely scattered through the lungs. The hyperplastic cells had abundant
      eosinophilic cytoplasm, vesicular nuclei and prominent nucleoli.
      Immunohistochemistry showed that they stained for cytokeratins AE1, AE3 and CAM
      5.2 and for epithelial membrane antigen (EMA), but not for carcinoembryonic
      antigen (CEA), S100, smooth muscle actin, CD68 and HMB-45. CONCLUSIONS: Although
      micronodular type II pneumocyte hyperplasia is usually of no clinical
      significance, in our patient the process was so florid as to cause respiratory
      failure, which was severe enough to necessitate lung transplantation.

PMID- 12207790
TI  - Ulcerative terminal ileitis after BCG therapy for bladder carcinoma.
AB  - AIM: We evaluated the aetiology of ulcerative ileitis in a 77-year-old patient
      receiving BCG therapy for recurring bladder carcinoma. METHODS AND RESULTS:
      Histological examination, laboratory data and the clinical history allowed us to
      exclude a classical cause such as Crohn's disease, tuberculosis or ischaemia. The
      important locoregional reaction suggests a BCG ileitis of the terminal ileum.
      Intestinal BCG ileitis has been exceptionally described after BCG vaccination.
      CONCLUSION: Our observation of ulcerative ileitis indicates that a digestive
      tract location is possible as a reaction to BCG therapy.

PMID- 12207791
TI  - 'T-cell-rich large B-cell lymphoma'-'histiocyte-rich, T-cell-rich large B-cell
      lymphoma'-'T-cell/histiocyte-rich large B-cell lymphoma': will we ever see the
      wood for the trees?

PMID- 12207792
TI  - Capsular vascular proliferation associated with thyroid paraganglioma.

PMID- 12207793
TI  - Chronic cholecystitis and myeloid metaplasia.

PMID- 12207794
TI  - Ceruminous gland tumour.

PMID- 12207795
TI  - Immunohistochemical study of a case of uterine leiomyoma showing massive lymphoid
      infiltration and localized vasculitis after LH-RH derivant treatment.

PMID- 12207797
TI  - Editorial.

PMID- 12207796
TI  - Functioning uterine sex cord tumour.

PMID- 12207798
TI  - Finding current best evidence: putting the 4Ss into searching.

PMID- 12207799
TI  - Lifestyle modification in Type 2 diabetes.

PMID- 12207800
TI  - Prevention of cardiovascular morbidity with angiotension receptor blockade: life
      after LIFE.

PMID- 12207801
TI  - No morbidity-mortality. Commentary.

PMID- 12207802
TI  - What's new in the journals?

PMID- 12207803
TI  - Advances in continuous in vivo glucose monitoring.

PMID- 12207804
TI  - General description and methods.

PMID- 12207805
TI  - IGT and IFG. Time for revision?

PMID- 12207806
TI  - Impaired glucose tolerance and impaired fasting glycaemia: the current status on
      definition and intervention.
AB  - A workshop was convened by the International Diabetes Federation to review the
      latest information relating to the risks associated with impaired glucose
      tolerance (IGT) and impaired fasting glycaemia (IFG) for future diabetes and
      cardiovascular disease (CVD). The workshop sought to address three questions: (i)
      are the current definitions of IGT and IFG appropriate; (ii) are IFG and IGT risk
      factors, risk markers or diseases; (iii) what interventions (if any) should be
      recommended for people with IFG and IGT? The determinants of elevated fasting
      glucose and 2-h plasma glucose in an oral glucose tolerance test (2-HPG) levels
      differ. Raised hepatic glucose output and a defect in early insulin secretion are
      characteristic of the former, and peripheral insulin resistance is most
      characteristic of the latter. Therefore, it is not surprising that the
      concordance between the categories of IFG and IGT is limited. In all prevalence
      studies to date only half or less of people with IFG have IGT, and even a lower
      proportion (20-30%) with IGT also have IFG. In the majority of populations
      studied, IGT is more prevalent than IFG, and there is a difference in phenotype
      and gender distribution between the two categories. IFG is substantially more
      common amongst men and IGT slightly more common amongst women. The prevalence of
      IFG tends to plateau in middle age whereas the prevalence of IGT rises into old
      age. Both IFG and IGT are associated with a substantially increased risk of
      developing diabetes, with the highest risk in people with combined IFG and IGT.
      Because IGT is commoner than IFG in most populations it is more sensitive (but
      slightly less specific) for identifying people who will develop diabetes. In most
      populations studied, 60% of people who develop diabetes have either IGT or IFG 5
      years or so before, with the other 40% having normal glucose tolerance at that
      time. The limited published data suggest that both isolated IFG (I-IFG) and
      isolated IGT (I-IGT) are similarly associated with cardiovascular risk factors,
      such as hypertension and dyslipidaemia, with the highest risk in those with
      combined IFG and IGT. However, some data have suggested that I-IGT is more
      strongly associated with hypertension and dyslipidaemia (features of the
      metabolic syndrome) than I-IFG. In unadjusted analyses both IFG and IGT are
      associated with CVD and total mortality. In separate analyses for fasting and 2
      HPG adjusted for other cardiovascular risk factors (from the DECODE study) there
      remains a continuous relationship between 2-HPG and mortality, but an independent
      relationship with fasting glucose is only found above 7.0 mmol/l. Glycated
      haemoglobin (HbA1c) levels are continuously and positively associated with CVD
      and total mortality independent of other CVD risk factors. Life style
      interventions, including weight loss and increased physical activity, are highly
      effective in preventing or delaying the onset of diabetes in people with IGT. Two
      randomized controlled trials of individuals with IGT found that life style
      intervention studies reduce the risk of progressing to diabetes by 58%. The oral
      hypoglycaemic drugs metformin and acarbose have also been shown to be effective,
      but less so than the life style measures. Similar data do not yet exist for the
      effectiveness of such interventions in people with I-IFG. Larger studies are
      required to evaluate the effects of interventions on cardiovascular outcomes in
      people with IGT. Cost effective strategies to identify people with IGT for
      intervention should be developed and evaluated. The use of simple risk scores to
      assess who should undergo an oral glucose tolerance test is one promising
      approach, although these will need to be population-specific. In conclusion, IGT
      and IFG differ in their prevalence, population distribution, phenotype, and risk
      of total mortality and CVD. The consensus of the workshop was: 1. The diagnostic
      thresholds for all categories of glucose intolerance should be revisited in the
      light of the latest evidence. There was no clear consensus (with current
      evidence) on whether IFG and IGT should be classified as diseases, but they
      clearly represent risk factors and risk markers for diabetes and CVD,
      respectively. 2. Both IGT and IFG are similarly associated with an increased risk
      of diabetes, but IGT is more strongly associated with CVD outcomes. 3. Risks are
      higher when IGT and IFG coexist. 4. Life style interventions are highly effective
      in delaying or preventing the onset of diabetes in people with IGT and may reduce
      CVD and total mortality, but the latter requires formal testing.

PMID- 12207807
TI  - Insulin: in search of a syndrome.
AB  - The insulin resistance syndrome has been defined as the clustering of
      hypertension, dyslipidaemia and impaired glucose tolerance in subjects with high
      fasting plasma insulin concentrations. The latter are usually taken as a
      surrogate measure of insulin resistance of whole-body glucose disposal. Although
      hyperinsulinaemia and insulin resistance are reciprocally related to one another,
      the association is not very strong. In the data-pooling project of the European
      Group for the study of Insulin Resistance (EGIR), clamp-derived insulin
      sensitivity (as the M value) and fasting plasma insulin concentrations were
      available in 1308 non-diabetic subjects with a wide range of age and body mass
      index. In this cohort, hyperinsulinaemia (as the upper quartile of fasting plasma
      insulin distribution in the non-obese segment of the population) and insulin
      resistance (as the bottom quartile of M value in the same subgroup) were each
      present in approximately 40% of the whole population, but identified only
      partially overlapping (60%) subsets of individuals. When the subjects with
      insulin resistance but without hyperinsulinaemia (n = 198) were compared with the
      subjects with hyperinsulinaemia but without insulin resistance (n = 267),
      significant differences emerged in the respective clinical phenotypes. Thus,
      subjects with 'pure' insulin resistance had a more central fat distribution and
      presented evidence of excessive lipolysis and endogenous glucose production. In
      contrast, subjects with 'pure' hyperinsulinaemia had suppressed lipolysis,
      endogenous glucose production and insulin clearance, higher values of systolic
      blood pressure and lower values of serum HDL-cholesterol concentrations. The only
      abnormality common to both phenotypes was the presence of raised serum
      triglycerides concentrations. This analysis indicates that hyperinsulinaemia and
      insulin resistance identify partially different subgroups of individuals in a non
      diabetic population, and suggests that hyperinsulinaemia and insulin resistance
      carry distinct pathogenic potential in terms of the components of the insulin
      resistance syndrome.

PMID- 12207808
TI  - Antibodies to GAD in Japanese patients classified as Type 2 diabetes at
      diagnosis. High titre of GAD Ab is a predictive marker for early insulin
      treatment--report of west Japan (Kyushu, Yamaguchi, Osaka) study for GAD Ab(+)
      diabetes.
AB  - AIM: We evaluated the prevalence of GAD Ab in Japanese Type 2 diabetic patients
      treated with oral hypoglycaemic agents (OHA) and/or diet and followed GAD Ab(+)
      patients to assess the usefulness of GAD Ab as a marker for future insulin
      treatment prospectively. METHODS: A total of 2658 Japanese Type 2 diabetic
      patients treated by OHA and/or diet were randomly selected between April 1996 and
      December 1998. The clinical characteristics at entry were assessed and patients
      were followed for 1-3 years. RESULTS: The overall prevalence of GAD Ab among Type
      2 diabetic patients was 2.0%. Forty-five had a history of diabetes of < or = 5
      years (short history) while those with duration > 5 years (long history) totalled
      nine. Among them, 47% of patients with a short history did not require insulin in
      the follow-up period. However, none of those with a long history required insulin
      treatment within 2 years. Comparison of patients based on GAD titre in those with
      short history showed that 33% of patients in the high-titre group (> or = 20 U)
      required no insulin treatment in the first year of follow-up. In contrast, this
      proportion was 80% in the first and 67% in the second year in the low-titre group
      (< 20 U). CONCLUSIONS: The prevalence of GAD Ab in Japanese patients with a short
      and long history of diabetes was 2.8% and 0.9%, respectively. The presence of GAD
      Ab in Japanese Type 2 diabetic patients with a short history of diabetes is a
      marker for early insulin treatment.

PMID- 12207809
TI  - Surrogate estimates of insulin sensitivity in Chinese diabetic patients and their
      offspring.
AB  - AIMS: To evaluate the relationship between surrogate measures of insulin
      sensitivity and results from euglycaemic insulin clamp in Chinese diabetic
      patients and their offspring. METHODS: The study included 59 volunteers from 20
      diabetic families. Each participant completed a 75-g oral glucose tolerance test
      (OGTT) and a euglycaemic insulin clamp. We tested the correlation of surrogate
      measures of insulin sensitivity with M-values and M/I ratios (the amount of
      glucose infused during 90-120 min of the clamp was defined as M, and the mean
      values of plasma insulin during 90-120 min as I) from the euglycaemic insulin
      clamp. These measures included fasting insulin (FPI), insulin at 120 min of OGTT,
      insulin area under the curve of OGTT, fasting glucose-to-insulin ratio,
      homeostasis model assessment for insulin sensitivity (HOMA-IR and HOMA %S) and
      the Matsuda-DeFronzo index from OGTT. RESULTS: The Matsuda-DeFronzo index closely
      correlated to M-value and M/I in 21 diabetic, 38 non-diabetic individuals and the
      59 participants overall (with M-value, r = 0.68, 0.84 and 0.84; with M/I, r =
      0.71, 0.72 and 0.75, respectively, all P < 0.001). Without OGTT, HOMA %S was a
      good surrogate index for diabetic (correlated to M-value and M/I, r = 0.71 and
      0.68, P = 0.001) and for non-diabetic subjects (to M-value, r = 0.73; to M/I, r =
      0.55, both P < 0.001). FPI was as good as HOMA %S and Matsuda-DeFronzo index.
      CONCLUSIONS: The Matsuda-DeFronzo index, HOMA %S and FPI are good surrogate
      estimates of insulin sensitivity in Chinese diabetic subjects and their
      offspring.

PMID- 12207810
TI  - Evaluation of a district-wide screening programme for diabetic retinopathy
      utilizing trained optometrists using slit-lamp and Volk lenses.
AB  - BACKGROUND: Debate exists about the optimum way to screen for diabetic
      retinopathy. Cameras produce a permanent record, but offer patients less choice
      about when and where to be screened. Optometrists offer flexibility but
      sensitivity and specificity of schemes have varied considerably, perhaps because
      of variability in screening methodology and that there is frequently no quality
      assurance programme. AIMS: To audit our district-wide (population 340000)
      screening programme for diabetic retinopathy against national targets:
      sensitivity > 80%, specificity > 95% and referral to review < 3 months. METHODS:
      Trained optometrists performed slit-lamp examination with Volk lenses (78
      dioptre) with standardized reporting. Audit was by ophthalmologist with slit-lamp
      and Volk lenses through dilated pupils. RESULTS: We examined 872 eyes of 439
      patients; 64% were normal, 29% background diabetic retinopathy, 7% sight
      threatening eye disease (STED). Sixty-three percent of patients were seen within
      6 months of the original screen. Of these, sensitivity for any retinopathy was
      72%, specificity 77%, positive predictive value (PPV) 53%, negative predictive
      value (NPV) 88%. For STED, in this group, sensitivity was 87% and specificity
      91%, PPV 30%, NPV 99%. Median interval referral to ophthalmological review was
      11.5 weeks with 73% reviewed in under the 13-week target. Of those referred 25%
      received laser therapy. Eleven patients found to have referable eye disease at
      their initial screen were not referred to an ophthalmologist by their GP.
      CONCLUSIONS: We conclude that effective district-wide screening for diabetic
      retinopathy by optometrists using slit-lamp and Volk lenses is possible; however,
      only 36% of identified people with diabetes in the district were screened over a
      4-year period.

PMID- 12207811
TI  - Less severe hypoglycaemia, better metabolic control, and improved quality of life
      in Type 1 diabetes mellitus with continuous subcutaneous insulin infusion (CSII)
      therapy; an observational study of 100 consecutive patients followed for a mean
      of 2 years.
AB  - AIMS: To compare glycaemic control, occurrence of acute complications, and
      diabetes-specific quality of life in Type 1 diabetic patients (on intensified
      conventional insulin treatment (ICT)) before and after initiation of CSII.
      METHODS: One hundred and three patients (58 women) started CSII between October
      1995 and April 1999 in our department. The indication for CSII was optimization
      of metabolic control and improvement of flexibility of life style (OF group) in
      60 patients (58%), and prevention of severe hypoglycaemia (HY group) in 43
      patients. Mean age at initiation of CSII was 33 +/- 11 years (OF 33 +/- 10, HY 33
      +/- 11 (mean +/- sd)), diabetes duration 18 +/- 9 years (OF 16 +/- 9, HY 20 +/-
      9). Three patients stopped CSII, mean duration of CSII of the remaining 100
      patients was 1.8 +/- 1.2 years. The occurrence of hypoglycaemia, ketoacidosis and
      skin abscesses was assessed retrospectively for the 12 months before starting
      CSII, and recorded continuously during CSII. Quality of life was assessed with a
      validated, diabetes-specific questionnaire before and after CSII in 50 patients.
      RESULTS: The incidence of serious hypoglycaemia (any external help) was reduced
      from 1.23 (OF 0.0; HY 2.93) during ICT to 0.29 cases/patient per year (OF 0.09;
      HY 0.55) during CSII. The incidence of severe hypoglycaemia (SH) (treated with
      i.v. glucose or glucagon injection) fell from 0.70 (OF 0.0; SH 1.67) during ICT
      to 0.06 cases/patient per year (OF 0.02; HY 0.12) during CSII. HbA1c improved
      from 7.7 +/- 1.1% to 7.2 +/- 1.0% (P < 0.001) (OF 7.8% vs. 7.2%; HY 7.6% vs.
      7.2%). During CSII the incidence of abscesses was 0.11 and of ketoacidosis 0.01
      cases/patient per year. Quality of life assessments showed significant
      improvement in all parameters during CSII. CONCLUSIONS: In our cohort of Type 1
      diabetic patients, we observed a substantial decrease of hypoglycaemia along with
      a significant fall of HbA1c. Quality of life on CSII was improved when compared
      with ICT.

PMID- 12207813
TI  - Heterogeneity in young adult onset diabetes: aetiology alters clinical
      characteristics.
AB  - AIMS: To describe the characteristics of hepatocyte nuclear factor (HNF) 1 alpha
      mutation carriers diagnosed with diabetes after 25 years and compare them with
      young-onset Type 2 diabetic patients (YT2D) diagnosed at the same age. SUBJECTS
      AND METHODS: We studied 44 (21 male, 23 female) patients with HNF-1 alpha
      mutations diagnosed with diabetes at ages 25-45 years and 44 YT2D subjects
      matched for sex and age of diagnosis. RESULTS: Median age of onset of diabetes
      was 35 years in both groups. The HNF-1 alpha group demonstrated: lower body mass
      index (25.1 vs. 30.7 kg/m2; P < 0.001) and lower fasting triglycerides (1.37 vs.
      2.96 mmol/l; P = 0.001) with similar fasting cholesterol level. They had lower
      glycated haemoglobin A1c (7.3 vs. 8.5%; P = 0.015) despite greater duration of
      diabetes (24 vs. 16 years; P = 0.02) and less frequent treatment with insulin
      (21% vs. 55%; P = 0.002). They were less likely to be treated for hypertension
      (13.3% vs. 56.3%; P = 0.009). Importantly, no difference was observed in reported
      parental history of diabetes between the two groups (65.9% vs. 63.6%; P = 0.92).
      Logistic regression showed that triglyceride levels and presence of anti
      hypertensive treatment were the most important independent variables.
      CONCLUSIONS: Patients with HNF-1 alpha mutations may present with diabetes as
      young adults between the ages of 25-45 years. In this age range a wide
      differential diagnosis of diabetes is observed. Conventional criteria of age of
      onset and family history will not differentiate HNF-1 alpha mutation carriers
      from YT2D subjects in this age range, but features of the metabolic syndrome, in
      particular fasting triglycerides and hypertension, are helpful. In patients
      diagnosed before 45 years without features of insulin resistance the diagnosis of
      HNF-1 alpha should be considered.

PMID- 12207812
TI  - Gliclazide improves anti-oxidant status and nitric oxide-mediated vasodilation in
      Type 2 diabetes.
AB  - AIMS: To evaluate the effects of gliclazide on oxidative status and vascular
      response to systemic administration of L-arginine, the natural precursor of
      nitric oxide (NO), in Type 2 diabetic patients. METHODS: Thirty Type 2 diabetic
      patients received glibenclamide (n = 15) or gliclazide (n = 15) in a 12-week,
      randomized, observer-blinded, parallel study. Plasma lipid peroxides, total
      radical-trapping anti-oxidant parameter (TRAP), and blood pressure responses to
      an intravenous bolus of L-arginine were measured pre- and post-treatment.
      RESULTS: At 12 weeks, gliclazide patients had lower plasma lipid peroxides (13.3
      +/- 3.8 micro mol/l vs. 19.2 +/- 4.3 micro mol/l; P = 0.0001) and higher plasma
      TRAP (1155.6 +/- 143.0 micro mol/l vs. 957.7 +/- 104.3 micro mol/l; P = 0.0001)
      than the glibenclamide patients. Gliclazide but not glibenclamide significantly
      reduced systolic and diastolic blood pressure (P = 0.0199 and P = 0.00199,
      respectively, two-way repeated measures analysis of variance) in response to
      intravenous L-arginine. CONCLUSIONS: Gliclazide reduces oxidative stress in Type
      2 diabetic patients by improving plasma anti-oxidant status. This effect is
      associated with enhanced NO-mediated vasodilation.

PMID- 12207814
TI  - The evaluation of screening policies for diabetic retinopathy using simulation.
AB  - AIMS: To develop a model for evaluating screening strategies and to use it to
      determine the cost effectiveness of varying the screening method and the
      screening interval. METHODS: A discrete event simulation was designed, validated
      and run for a population of 500000. Most parameters were derived from peer
      reviewed publications. RESULTS: Standard methods of screening save up to 50% of
      the potential sight years lost. They give up to 85% of the sight years saved by
      an idealized gold standard programme using mydriatic seven-field photography
      reported by an ophthalmologist. The mobile camera, used for annual screening and
      6-month follow-up after the detection of background retinopathy, had an estimated
      cost of pound 449200 per year with pound 2842 per sight year saved. It is less
      efficient to screen Type 2, rather than Type 1 diabetes mellitus patients, but
      they contributed to almost three-quarters of the sight years saved. CONCLUSIONS:
      The model can evaluate screening intervals and methods on a national or health
      authority basis. Results indicate that it appears more cost effective to continue
      to screen outside an ophthalmology clinic, until treatment is needed. Programmes
      with annual screening, and more frequent screening for those with background
      retinopathy, are robust to realistic fluctuations in compliance and screening
      sensitivity.

PMID- 12207815
TI  - Longitudinal assessment of the development of diabetic polyneuropathy and
      associated risk factors.
AB  - AIMS: To longitudinally assess risk factors for diabetic polyneuropathy (DPN)
      severity, and to longitudinally assess risk factors for the change of DPN
      severity during 2-4 years of follow-up. METHODS: From 1995 to 1999, 486 Type 2
      diabetes patients in general practice were examined annually with regard to DPN
      severity and its possible risk factors. DPN severity was assessed with a clinical
      neurological examination (CNE) which included pinprick sense, light touch sense,
      vibration sense and ankle jerk. Longitudinal (multivariate) linear associations
      of (change of) CNE score and predicting variables were analysed using multilevel
      analyses. RESULTS: In this population, 50% of participants were men and had a
      mean age of 65.4 years, almost one-third (31.7%) of the participants had a CNE
      score > 4 at baseline and were classified with DPN. CNE score significantly
      increased during follow-up. Among participants not graded with DPN at baseline,
      21.3% progressed towards a CNE score > 4 after 3 years of follow-up. Longitudinal
      multivariate analyses showed that age, diabetes duration, HbA1c, height, body
      mass index and ankle-arm index together best predicted CNE score during follow
      up. Change of CNE score during follow-up was best predicted by age, diabetes
      duration and HbA1c, with the latter being the strongest predictor. CONCLUSIONS:
      Although several factors are longitudinally associated with DPN, HbA1c, age and
      diabetes duration were the best predictors of CNE change during follow-up.
      Therefore, improving glycaemia remains an important amenable factor in preventing
      worsening of diabetic polyneuropathy.

PMID- 12207816
TI  - Diabetic ketosis activates lymphomonocyte-inducible nitric oxide synthase.
AB  - AIMS: Inappropriate production of nitric oxide (NO) may be responsible for the
      haemodynamic disturbances of diabetic ketoacidosis. We investigated whether this
      metabolic condition is associated with increased plasma nitrate (the stable
      oxidation product of NO) levels and NO synthase gene expression in
      lymphomonocytes. RESEARCH DESIGN AND METHODS: Plasma nitrate concentrations,
      lymphomonocyte-inducible nitric oxide synthase (iNOS) gene expression, tumour
      necrosis factor-alpha (TNF-alpha) and soluble thrombomodulin were measured in 11
      Type 1 diabetic patients at baseline, during mild ketosis and after euglycaemia
      was re-established. RESULTS: During diabetic ketosis plasma nitrate
      concentrations were higher (18 (16-21) vs. 9 (7-11) micro mol/l; (95% lower-upper
      confidence interval) P < 0.05) than at baseline. At baseline lymphomonocyte iNOS
      mRNA expression and iNOS protein levels were undetectable, but in ketosis both
      were increased (both at P < 0.0001). After recovery from ketosis, NO3
      concentration, iNOS mRNA, and iNOS expression (270 +/- 36%, mean +/- sd)
      decreased but not significantly. No significant changes were observed in either
      TNF-alpha or soluble thrombomodulin levels between the three conditions.
      CONCLUSIONS: Diabetic ketosis is associated with increased nitrate levels and the
      activation of iNOS expression in circulating lymphomonocytes, but it does not
      affect either the proinflammatory cytokine TNF-alpha or a marker of endothelial
      dysfunction such as thrombomodulin. Our data support the hypothesis that, during
      diabetic ketosis, alterations in NO homeostasis are present in circulating
      lymphomonocytes.

PMID- 12207817
TI  - Age of onset possibly associated with the degree of heteroplasmy in two male
      siblings with diabetes mellitus having an A to G transition at 3243 of
      mitochondrial DNA.
AB  - We describe two male siblings with diabetes mellitus caused by mitochondrial 3243
      mutation. The level of heteroplasmy in peripheral blood leucocytes was determined
      by a last-cycle hot PCR method. The younger brother, who had 39% heteroplasmy,
      developed diabetes at age of 25, and demonstrated a lean body habitus and blunted
      insulin secretion. The elder brother, who had 22% heteroplasmy, was diagnosed at
      the age of 42. The younger brother showed a higher increment of serum lactate
      after exercise. In these siblings the level of heteroplasmy in their peripheral
      blood leucocytes appeared to be associated with age of onset of diabetes.

PMID- 12207818
TI  - Ambulatory blood pressure monitoring: is it necessary for the routine assessment
      of hypertension in people with diabetes?
AB  - AIMS: The British Hypertension Society (BHS) has recommended that, for people
      with diabetes, the target 'clinic' blood pressure should be < 140/80 mmHg.
      Ambulatory monitoring of blood pressure (ABPM) is used widely in the assessment
      of hypertension and the BHS has recommended that the target 'awake' ambulatory
      blood pressure for people with diabetes should be < 130/75 mmHg. The purpose of
      the present study was to determine the utility of ABPM in the assessment of
      hypertension in patients with diabetes, over and above a careful 'clinic'
      measurement of blood pressure. METHODS: The records of 540 patients with diabetes
      who underwent ABPM (using SpaceLabs monitors) were retrospectively analysed. With
      respect to current BHS recommendations, the positive and negative predictive
      values of 'clinic' blood pressure (measured by trained nurses using mercury
      sphygmomanometers) on 'awake' ambulatory blood pressure (ABP) were calculated.
      RESULTS: The positive predictive value of the 'clinic' BP, its ability to detect
      patients whose ABP was above BHS targets, was 99%. The negative predictive value
      of 'clinic' blood pressure was 27%. CONCLUSIONS: With regard to current BHS
      guidelines, ABPM is generally unnecessary in the assessment of hypertension in
      patients with diabetes, provided careful 'clinic' measurements of blood pressure
      are made.

PMID- 12207819
TI  - Anti-diabetogenic effect of the human amylin analogue, pramlintide, in Type 1
      diabetes is not mediated by GLP-1.

PMID- 12207820
TI  - Type 2 diabetes with onset in the elderly is not a benign disease.

PMID- 12207821
TI  - A case of congenital generalized lipodystrophy with lipoatrophic diabetes
      developing anti-insulin antibodies.

PMID- 12207822
TI  - The Houssay phenomenon, another clue to Sheehan's syndrome in a diabetic.

PMID- 12207823
TI  - The C282Y/wt heterozygous HFE genotype is associated with lower blood pressure
      and HDL-cholesterol in Type 2 diabetes.

PMID- 12207826
TI  - Optimizing antibiotics in residents of nursing homes: protocol of a randomized
      trial.
AB  - BACKGROUND: Antibiotics are frequently prescribed for older adults who reside in
      long-term care facilities. A substantial proportion of antibiotic use in this
      setting is inappropriate. Antibiotics are often prescribed for asymptomatic
      bacteriuria, a condition for which randomized trials of antibiotic therapy
      indicate no benefit and in fact harm. This proposal describes a randomized trial
      of diagnostic and therapeutic algorithms to reduce the use of antibiotics in
      residents of long-term care facilities. METHODS: In this on-going study, 22
      nursing homes have been randomized to either use of algorithms (11 nursing homes)
      or to usual practise (11 nursing homes). The algorithms describe signs and
      symptoms for which it would be appropriate to send urine cultures or to prescribe
      antibiotics. The algorithms are introduced by inservicing nursing staff and by
      conducting one-on-one sessions for physicians using case-scenarios. The primary
      outcome of the study is courses of antibiotics per 1000 resident days. Secondary
      outcomes include urine cultures sent and antibiotic courses for urinary
      indications. Focus groups and semi-structured interviews with key informants will
      be used to assess the process of implementation and to identify key factors for
      sustainability.

PMID- 12207827
TI  - Medical informatics in an undergraduate curriculum: a qualitative study.
AB  - BACKGROUND: There is strong support for educating physicians in medical
      informatics, and the benefits of such education have been clearly identified.
      Despite this, North American medical schools do not routinely provide education
      in medical informatics. METHODS: We conducted a qualitative study to identify
      issues facing the introduction of medical informatics into an undergraduate
      medical curriculum. Nine key informants at the University of Toronto medical
      school were interviewed, and their responses were transcribed and analyzed to
      identify consistent themes. RESULTS: The field of medical informatics was not
      clearly understood by participants. There was, however, strong support for
      medical informatics education, and the benefits of such education were
      consistently identified. In the curriculum we examined, medical informatics
      education was delivered informally and inconsistently through mainly optional
      activities. Issues facing the introduction of medical informatics education
      included: an unclear understanding of the discipline; faculty and administrative
      detractors and, the dense nature of the existing undergraduate medical
      curriculum. CONCLUSIONS: The identified issues may present serious obstacles to
      the introduction of medical informatics education into an undergraduate medicine
      curriculum, and we present some possible strategies for addressing these issues.

PMID- 12207828
TI  - Is council tax valuation band a predictor of mortality?
AB  - BACKGROUND: All current UK indices of socio-economic status have inherent
      problems, especially those used to govern resource allocation to the health
      sphere. The search for improved markers continues: this study proposes and tests
      the possibility that Council Tax Valuation Band (CTVB) might match requirements.
      PRESENTATION OF THE HYPOTHESIS: To determine if there is an association between
      CTVB of final residence and mortality risk using the death registers of a UK
      general practice. TESTING THE HYPOTHESIS: Standardised death rates and odds
      ratios (ORs) for groups defined by CTVB of dwelling (A - H) were calculated using
      one in four denominator samples from the practice lists. Analyses were repeated
      three times - between number of deaths and CTVB of residence of deceased 1992 -
      1994 inclusive, 1995 - 1997 inc., 1998 - 2000 inc. In 856 deaths there were
      consistent and significant differences in death rates between CTVBs: above
      average for bands A and B residents; below average for other band residents.
      There were significantly higher ORs for A, B residents who were female and who
      died prematurely (before average group life expectancy). IMPLICATIONS OF THE
      HYPOTHESIS: CTVB of final residence appears to be a proxy marker of mortality
      risk and could be a valuable indicator of health needs resource at household
      level. It is worthy of further exploration.

PMID- 12207830
TI  - Achieving physiological change in school-based intervention trials: what makes a
      preventive intervention successful?

PMID- 12207829
TI  - Development of real-time NASBA assays with molecular beacon detection to quantify
      mRNA coding for HHV-8 lytic and latent genes.
AB  - BACKGROUND: Human herpesvirus-8 (HHV-8) is linked to the pathogenesis of Kaposi's
      sarcoma (KS), and the HHV-8 DNA load in peripheral blood mononuclear cells (PBMC)
      is associated with the clinical stage of KS. To examine the expression of HHV-8
      in PBMC, four HHV-8 mRNA specific NASBA assays were developed METHODS: We have
      developed four quantitative nucleic acid sequence-based amplification assays
      (NASBA-QT) specifically to detect mRNA coding for ORF 73 (latency-associated
      nuclear antigen, LANA), vGCR (a membrane receptor), vBcl-2 (a viral inhibitor of
      apoptosis) and vIL-6 (a viral growth factor). The NASBA technique amplifies
      nucleic acids without thermocycling and mRNA can be amplified in a dsDNA
      background. A molecular beacon is used during amplification to enable real-time
      detection of the product. The assays were tested on PBMC samples of two AIDS-KS
      patients from the Amsterdam Cohort. RESULTS: For all four assays, the limit of
      detection (LOD) of 50 molecules and the limit of quantification (LOQ) of 100
      molecules were determined using in vitro transcribed RNA. The linear dynamic
      range was 50 to 10(7) molecules of HHV-8 mRNA. We found HHV-8 mRNA expression in
      9 out of the 10 tested samples. CONCLUSION: These real-time NASBA assays with
      beacon detection provide tools for further study of HHV-8 expression in patient
      material.

PMID- 12207832
TI  - Olive oil phenolics: effects on DNA oxidation and redox enzyme mRNA in prostate
      cells.
AB  - Hydroxytyrosol, tyrosol and caffeic acid effects on hydrogen peroxide-induced DNA
      damage, hydroperoxide generation and redox enzyme gene expression were studied in
      oxidative-stress-sensitive human prostate cells (PC3). Hydroxytyrosol led to
      lower levels of hydroperoxides, DNA damage, and mRNA levels of classic
      glutathione peroxidase (GPx) for all the studied concentrations. Only
      hydroxytyrosol was effective at low concentrations (10 microm). Tyrosol reduced
      DNA oxidation only at high (>50 microm) concentrations and increased
      hydroperoxides, GPx and phospholipid hydroperoxide GPx mRNA levels. Caffeic acid
      elicited effects between those of the other two phenolics. Results indicate that
      hydroxytyrosol is the only significant antioxidant phenolic in olive oil and may
      be the major component accounting for its beneficial properties. Tyrosol appeared
      to exhibit pro-oxidant effects (only at high concentrations) and caffeic acid was
      neutral. Both number and position of hydroxyl groups appear to play a role in the
      cellular effects of hydroxytyrosol.

PMID- 12207833
TI  - Intestinal absorption of different types of folate in healthy subjects with an
      ileostomy.
AB  - Our knowledge on the absorption of folate is incomplete. The deconjugation
      process as a possible limiting factor in the absorption of folates was
      investigated. The study also attempted to validate the use of the area under the
      serum response curve (AUC) from food compared with folic acid as a proxy variable
      for food folate bioavailability. Folate absorption was determined in healthy
      ileostomy volunteers (n 11) using a single-dose short-term protocol. In a
      randomised crossover design, volunteers received spinach meals and a supplement.
      Based on analysis of test meals and ileostomy effluents, there was no difference
      in folate absorption between spinach with a mono-:polyglutamate ratio 40:60 and
      the same spinach with a 100:0 ratio. The absolute absorption of spinach folate
      (79 %) calculated from the difference between folate intake and folate content of
      ileostomy effluents was approximately equal to the relative absorption (81 %)
      calculated from the AUC after consumption of spinach meals in relation to the AUC
      after consumption of the folic acid supplement. We conclude that the
      deconjugation process is not a limiting factor in the absorption of spinach
      folates. Comparison of AUC of food folate v. folic acid in a short-term protocol
      may be suitable for assessing food folate bioavailability.

PMID- 12207834
TI  - The effect of dietary supplementation using isomeric blends of conjugated
      linoleic acid on lipid metabolism in healthy human subjects.
AB  - Conjugated linoleic acid (CLA) refers to a group of positional and geometric
      isomers of linoleic acid. Studies using animal models have shown that CLA reduces
      adiposity, improves plasma lipoprotein metabolism and insulin sensitivity and
      reduces arteriosclerosis. Whilst CLA may have therapeutic potential with regard
      to coronary artery disease risk factors in human subjects, there has been little
      investigation into its effects in human subjects. This current study investigated
      the effects of dietary supplementation using two isomeric blends of CLA on
      triacylglycerol (TAG)-rich lipoprotein metabolism and reverse cholesterol
      transport in human subjects and evaluates whether CLA modulated cardiovascular
      disease risk factors. Fifty-one normolipidaemic subjects participated in this
      randomised double-blind placebo-controlled intervention trial. Subjects were
      randomly assigned to receive 3 g cis-9,trans-11-trans-10,cis-12 isomeric blend
      (50 : 50) or a cis-9,trans-11-trans-10,cis-12 isomeric blend (80 : 20) CLA or
      linoleic acid (control)/d for 8 weeks. The 50 : 50 CLA isomer blend significantly
      reduced (P<or=0.005) fasting plasma TAG concentrations. The 80 : 20 CLA isomer
      blend significantly reduced (P<or=0.05) VLDL-cholesterol concentrations. CLA
      supplementation had no significant effect on LDL-cholesterol, HDL-lipid-protein
      composition or reverse cholesterol transport. CLA supplementation had no effect
      on body weight, plasma glucose and insulin concentrations. Fatty acid analysis
      revealed that the cis-9,trans-11 CLA isomer was incorporated into total plasma
      lipids following supplementation with both isomeric blends of CLA. The present
      study demonstrates that CLA supplementation significantly improves plasma TAG and
      VLDL metabolism in human subjects. The study confirms that some of the cardio
      protective effects of CLA that were shown in animal studies are relevant to man.

PMID- 12207835
TI  - Effects of folic acid and vitamin B12 supplements on folate and homocysteine
      metabolism in pigs during early pregnancy.
AB  - The present experiment aimed to determine the effects of supplements of folic
      acid (FA) alone or in combination with vitamin B12 on folate and homocysteine
      metabolism in gestating nulliparous Yorkshire-Landrace (YL) and multiparous
      Landrace (LD) occidental sows and multiparous Chinese Meishan-Landrace (ML) sows.
      LD sows were randomly assigned to two treatments: 0 or 15 mg FA/kg diet while YL
      and ML sows were assigned to three treatments: 0 mg FA/kg diet, 15 mg FA/kg or 15
      mg vitamin B12/kg diet. Supplements were given from the oestrus preceding
      insemination up to slaughter on day 15 of gestation. At slaughter, a uterine
      flush was collected to determine uterine contents of homocysteine, methionine,
      tetrahydrofolate (THF), 5-methyl-THF, pyridoxal 5-phosphate (P5P) and vitamin
      B12. Blood samples were taken at first oestrus, at insemination and on days 5, 10
      and 15 of gestation to determine plasma concentrations of homocysteine,
      methionine, THF, 5-methyl-THF, P5P, vitamin B12 and relative total folate-binding
      capacity. In occidental sows (YL and LD), the FA supplement tended to decrease
      uterine flush content of homocysteine (P=0.06) and concentrations of plasma
      homocysteine (P=0.09). Nulliparous YL sows had lower concentrations of plasma
      homocysteine, methionine, THF and 5-methyl-THF (P<0.05) than multiparous LD sows.
      Multiparous ML and LD sows had similar concentrations of plasma THF, 5-methyl
      THF, methionine and vitamin B12, but ML sows had lower concentrations of plasma
      homocysteine (P<0.05). The vitamin B12 supplement increased concentrations of
      plasma vitamin B12 (P<0.05) both in multiparous ML and nulliparous YL sows, but
      had no effect on the composition of either uterine flush or plasma. The present
      results showed also that sows had a low vitamin B12 status (<200 pg/ml) and high
      circulating homocysteine levels (>15 microm) during the first 15 d of gestation.
      Furthermore, the vitamin B12 content in uterine secretions represented between
      180 and 300 % of the total content in plasma. The low plasma concentrations of
      homocysteine in multiparous ML sows suggest a more efficient remethylation
      pathway which may not be dependent upon dietary supply of FA or vitamin B12. In
      nulliparous YL sows, low concentrations of both homocysteine and methionine
      suggest that the methionine requirement for protein deposition might have reduced
      the amount of methionine available for the methylation pathway. The results of
      the present experiment suggest that the reduction of uterine homocysteine may be
      an important aspect of the role of FA supplement on the uterine environment in
      occidental sows. The presence of high levels of vitamin B12 in uterine secretions
      merits further investigation in relation to embryonic development.

PMID- 12207836
TI  - Dietary antioxidants and DNA damage in patients on long-term acid-suppression
      therapy: a randomized controlled study.
AB  - Free radicals and reactive species produced in vivo can trigger cell damage and
      DNA modifications resulting in carcinogenesis. Dietary antioxidants trap these
      species limiting their damage. The present study evaluated the role of vitamins C
      and E in the prevention of potentially premalignant modifications to DNA in the
      human stomach by supplementing patients who, because of hypochlorhydria and
      possible depletion of gastric antioxidants, could be at increased risk of gastric
      cancer. Patients undergoing surveillance for Barrett's oesophagus (n 100), on
      long-term proton pump inhibitors were randomized into two groups: vitamin C (500
      mg twice/d) and vitamin E (100 mg twice/d) for 12 weeks (the supplemented group)
      or placebo. Those attending for subsequent endoscopy had gastric juice, plasma
      and mucosal measurements of vitamin levels and markers of DNA damage. Seventy-two
      patients completed the study. Plasma ascorbic acid, total vitamin C and vitamin E
      were elevated in the supplemented group consistent with compliance. Gastric juice
      ascorbic acid and total vitamin C levels were raised significantly in the
      supplemented group (P=0.01) but supplementation had no effect on the mucosal
      level of this vitamin. However, gastric juice ascorbic acid and total vitamin C
      were within normal ranges in the unsupplemented group. Mucosal malondialdehyde,
      chemiluminescence and DNA damage levels in the comet assay were unaffected by
      vitamin supplementation. In conclusion, supplementation does not affect DNA
      damage in this group of patients. This is probably because long-term inhibition
      of the gastric proton pump alone does not affect gastric juice ascorbate and
      therefore does not increase the theoretical risk of gastric cancer because of
      antioxidant depletion.

PMID- 12207837
TI  - Tobacco and alcohol consumption: impact on other cardiovascular and cancer risk
      factors in a southern European Mediterranean population.
AB  - Tobacco and alcohol consumption are strongly related to other cardiovascular and
      cancer risk factors. The aim of the present study was to analyse the association
      of nutrient intake, blood lipid variables and leisure-time physical activity with
      tobacco and alcohol consumption status. Participants were recruited in a cross
      sectional population-based survey, including cardiovascular risk factor
      measurements and evaluation of physical activity and diet intake in a
      Mediterranean population (n 1748). Multiple linear regression analysis, adjusted
      for several confounders, showed a direct association of saturated fatty acids (g
      and % total energy intake), dietary cholesterol intakes and serum triacylglycerol
      with smoking. An inverse association was observed for smoking and unsaturated
      fatty acids (% energy intake), vitamin C, alpha-tocopherol and beta-carotene
      intakes, leisure-time physical activity and HDL-cholesterol. These associations
      were not observed for alcohol drinking. After adjusting for the confounders
      earlier mentioned, low dietary intakes of vitamin C and dietary fibre were more
      likely in heavy-smokers as compared with non-smokers (odds ratio 1.74 (95 % CI
      1.07, 2.73) and 1.94 (95 % CI 1.29, 2.92) of low vitamin C (<60 mg/d) and dietary
      fibre intakes (<10 g/d) respectively). Alcohol consumption was directly
      associated with HDL-cholesterol and triacylglycerol, and attenuated the effects
      of smoking on HDL-cholesterol. These results suggest that the dietary intake of
      fibre and several antioxidant components of the Mediterranean diet is reduced in
      smokers, who also show an adverse lipid profile. However, the worst
      triacylglycerol levels are associated with the combination of heavy smoking and
      heavy alcohol drinking. Moderate alcohol consumption was not associated with an
      unhealthy diet pattern or adverse lipid profile. The health benefits of the
      Mediterranean diet appear to be strongly counteracted by smoking.

PMID- 12207838
TI  - Long-term programming of blood pressure by maternal dietary iron restriction in
      the rat.
AB  - We have reported that blood pressure was elevated in 3-month-old rats whose
      mothers were Fe-restricted during pregnancy. These animals also had improved
      glucose tolerance and decreased serum triacylglycerol. The aim of the present
      study was to determine whether these effects of maternal nutritional restriction,
      present in these animals at 3 months of age, can be observed in the same animals
      in later life. Pulmonary and serum angiotensin converting enzyme (ACE)
      concentrations were also measured to investigate whether the renin-angiotensin
      system was involved in the elevation of blood pressure observed in the offspring
      of Fe-restricted dams. Systolic blood pressure was higher in the offspring of Fe
      restricted dams at 16 months of age. Heart and kidney weight were increased as a
      proportion of body weight in the offspring of Fe-restricted dams. The pulmonary
      ACE concentration was not significantly different between the groups. The serum
      ACE concentration was significantly elevated in the offspring of Fe-restricted
      dams at 3 but not 14 months of age. There was a strong correlation between serum
      ACE levels at 3 and 14 months of age. Glucose tolerance and serum insulin were
      not different between the maternal diet groups. Serum triacylglycerol tended to
      be lower in the offspring of Fe-restricted dams. There were no differences in
      serum non-esterified fatty acids or serum cholesterol between the maternal diet
      groups. This study provides further evidence that maternal nutrition has effects
      on the offspring that persist throughout life. At 16 months of age, the elevation
      of blood pressure in Fe-restricted offspring does not appear to be mediated via
      changes in ACE levels. Both cardiac hypertrophy and decreased serum
      triacylglycerol have also been observed in Fe-restricted fetuses, suggesting that
      these changes may be initiated in utero.

PMID- 12207839
TI  - Effects of dietary lipids on immune function in a murine sensitisation model.
AB  - We have tested the effect of dietary fatty acids on aspects of innate and
      specific adaptive T helper (Th) 1- and Th2-driven immune responses in a murine
      sensitisation model using dinitrochlorobenzene as sensitiser. Six groups of
      fifteen BALB/c mice were fed diets containing 30 % fat (by energy) for 8 weeks.
      Diets were rich in saturated fatty acids, n-6 polyunsaturated fatty acid (PUFA),
      or n-3 PUFA, each at a sufficient (11, 35 and 68 mg/kg) and a supplemented
      vitamin E level (1028, 1031 and 1030 mg/kg respectively). Feeding n-6 PUFA
      marginally decreased % phagocytosing cells at the low vitamin E level, but had no
      other effects on immune function. The n-3 PUFA diets decreased production of
      prostaglandin E2 while increasing oxidative burst and tumour necrosis factor
      alpha production. In addition adaptive Th1-driven responses (immunoglobulin,
      Ig)G2a, IgG2b, interferon-gamma:interleukin 4) were decreased, whereas Th2-driven
      and mucosal immune responses were increased (IgE) or unaffected (IgG1, IgA).
      Combination with high levels of alpha-tocopherol did not affect the reduced
      prostaglandin E2 production, augmented the increase of tumour necrosis factor
      alpha production and tended to ameliorate the selective suppressive effects of n
      3 PUFA on certain Th1-driven effects (interferon-gamma:interleukin 4 ratio and
      IgG2a levels). We conclude that the sensitisation model appears useful for
      application in nutrition research. It allows a broad assessment of the effects of
      dietary intervention on various aspects of immune responsiveness, and as such
      provides a valuable model to assess, characterise and rank effects of foods
      and/or nutrients on a range of immune functions, including Th1-Th2 polarisation.

PMID- 12207840
TI  - Energy metabolism of young rats after early postnatal overnutrition.
AB  - Early postnatal overnutrition (PNO) induced by restricting litter size in rats
      leads to increased body-weight (BW) and body-fat gain in later life. PNO rats are
      used as an animal model of moderate obesity and early hyperinsulinism. We
      investigated whether the increased adiposity could be due to a decreased energy
      expenditure. Male newborn Wistar rats were raised in litters of either two (SL)
      or twelve pups (NL), weaned at 4 weeks of age and subsequently fed ad libitum. BW
      was recorded continuously until 12 weeks of age. Daily energy intake, total daily
      energy expenditure (EE, measured by indirect calorimetry) and body composition
      were measured in weaned pups at 5, 8 and 12 weeks of age. SL rats displayed
      increased BW compared with NL rats from week 2 to 5 and again from week 10 to 12.
      Lean body mass, body fat and protein content and total EE were increased in SL
      rats at week 5. The same linear correlation described the relationship between BW
      and total EE in NL and SL rats. At week 8 to 12 no differences in energy
      metabolism could be found, but the total fat content was increased in SL rats at
      week 12. Energy balance, i.e. assimilated energy minus EE, was no different
      between SL and NL at any time that it was measured. We conclude that although PNO
      rats display increased adiposity in early life, there seem to be no long-lasting
      effects on energy metabolism in later life, even if a tendency to increased
      adiposity can still be detected.

PMID- 12207841
TI  - Non-esterified fatty acid levels and physical inactivity: the relative importance
      of low habitual energy expenditure and cardio-respiratory fitness.
AB  - The fasting concentration of non-esterified fatty acids (NEFA) and the degree to
      which it declines during an oral glucose tolerance test are closely associated
      with insulin resistance and glucose intolerance. However, relatively few studies
      have described possible environmental determinants of NEFA concentrations.
      Physical activity is likely to be related to NEFA levels, but habitual activity
      level is difficult to quantify in epidemiological studies. In particular, it is
      unclear whether NEFA is more closely related to cardio-respiratory fitness or to
      habitual energy expenditure. In order to quantify these relationships, we
      analysed data from the Ely prospective population-based study in which 931
      subjects underwent a glucose tolerance test with measurements of cardio
      respiratory fitness and 4 d energy expenditure by heart-rate monitoring, a
      technique previously validated against whole-body calorimetry and doubly-labelled
      water. In order to estimate the latent variables of usual fitness and energy
      expenditure, a subset of 190 subjects underwent repeat testing on three further
      occasions over 1 year. In analyses adjusting only for age and sex, energy
      expenditure and cardio-respiratory fitness were both negatively correlated with
      the total area under the NEFA curve following the oral glucose load (standardised
      beta coefficients -0.030 and -0.039 respectively; both P<0.001) However, further
      adjustment for degree of obesity and bivariate measurement error suggested that
      the effect of energy expenditure was significantly greater than that for fitness
      (-0.047 and -0.005 respectively). These results suggest that the area under the
      NEFA curve in the oral glucose tolerance test, a measure of insulin sensitivity,
      is strongly associated with the habitual level of physical activity.

PMID- 12207842
TI  - Health and nutrition education in primary schools of Crete: changes in chronic
      disease risk factors following a 6-year intervention programme.
AB  - The effectiveness of a health and nutrition education programme, in changing
      certain chronic disease risk factors, was assessed after the 6 years intervention
      period was completed. The school-based intervention programme was applied to all
      children registered in the first grade (age 5.5-6.5 years) in 1992 in two
      counties of Crete, while the children from a third county served as a control
      group. In order to assess the effectiveness of the intervention, a variety of
      biological and behavioural parameters were measured before and following
      completion of the intervention in a randomly selected school-based sample of 602
      intervention group (IG) and 444 control group (CG) pupils. At the end of the 6
      year period, it was found that biochemical indices generally improved
      significantly more in the IG compared with the CG (mean change for IG v. CG was 
      0.27 v. -0.12 mmol/l for total cholesterol (TC); -0.07 v. +0.24 for TC:HDL and 
      0.13 v. +0.14 for LDL:HDL). Similarly, the changes observed in the anthropometric
      variables in the two groups were in favour of the IG (+3.68 v. +4.28 kg/m2 for
      BMI; +2.97 v. +4.47 mm for biceps skinfold). Total energy intake and consumption
      of total fat and saturated fat increased significantly less in the IG compared
      with the CG (+747.7 v. 1534.7 kJ (+178.7 v. +366.8 kcal); +5.9 v. +18.8 g and
      +0.8 v. +5.1 g respectively), while time devoted to leisure time physical
      activity and cardiovascular run test performance increased significantly more in
      the IG (+281 v. +174 min/week and +2.5 v. +1.2 stages respectively). The findings
      of the present study underline the importance of such programmes in health
      promotion and disease prevention. Although the long-term effects of these
      programmes can only be assessed by tracking this population through to
      adolescence and adulthood, these programmes seem to have the potential to lead to
      a healthier lifestyle and thus a reduction in risk factor levels.

PMID- 12207843
TI  - Measurement of total body water using 2H dilution: impact of different
      calculations for determining body fat.
AB  - This study estimated total body water (TBW) in four groups (twelve per group;
      sedentary and highly trained men and women) at the time of 2H dosing (T0) and
      after a 3.5 h equilibration period (Teq). Standard TBW calculations were employed
      at T0 (no correction for disproportionate urinary tracer loss) and Teq
      (correction for urinary tracer loss only), plus those calculations that corrected
      for a disproportionate urinary tracer loss and insensible tracer loss
      respectively. The measurement of body density enabled the four TBW estimates to
      be compared for the determination of three-compartment % body fat (BF). The very
      small difference between the standard and corrected T0 TBW data was not
      significant (P=0.914) and no GroupxTBW interaction was identified (P=0.125).
      These results reflect the closeness of the 2H concentration in the urine produced
      during the equilibration period and the Teq saliva samples. The associated mean %
      BF values were essentially identical. Although correcting for insensible 2H
      losses in addition to urinary losses at Teq produced a statistically significant
      (P<0.001) lower mean TBW (about 200 g) than the standard calculation, this
      translated to a small difference in % BF (0.3). The larger difference (about 500
      g, P<0.001) between the two (T0, Teq) corrected TBW calculations was also
      associated with a small body composition difference (0.1 % BF), which was less
      than the propagated error (0.3 % BF) for the three-compartment body composition
      model. Corrections to the standard calculations of TBW at T0 and Teq for a
      protocol employing a brief equilibration period (3.5 h) were therefore of
      marginal use for improving the accuracy of % BF estimates. The TBW difference
      over time (T0 v. Teq) also had little impact on % BF values.

PMID- 12207844
TI  - The role of de novo lipogenesis in development of obesity in man.

PMID- 12207848
TI  - Botulinum toxin therapy for myofascial pain disorders.
AB  - Myofascial pain disorder can originate from various muscles in the body. Numerous
      therapeutic approaches have been used to treat myofascial pain syndrome with
      varying success. Botulinum toxin neurolysis may become an important treatment
      regimen because it sustains relaxation of muscles. There is a growing body of
      clinical evidence for the efficacy of botulinum toxin in the treatment of painful
      myofascial conditions. The conditions that have been investigated include chronic
      low back pain, chronic cervical-associated headache, myofascial pain, myofascial
      pain syndrome and pain from chronic muscle spasm, and refractory myofascial pain.
      One of these studies was an open-label, exploratory pilot study into the
      cervicothoracic and lumbosacral regions using a novel injection technique.

PMID- 12207849
TI  - Post-traumatic myofascial pain of the head and neck.
AB  - Post-traumatic myofascial pain describes the majority of chronic head and neck
      pain seen in clinical practice. If conditions such as vascular headaches,
      neuropathic pain, degenerative cervical joint disease, and dental pain are
      excluded, myofascial tissues are directly or indirectly involved in all other
      forms of head and neck pain. The most common of these include temporomandibular
      disorders, neck pain such as whiplash-associated disorder, cervicogenic
      headaches, and tension-type headaches. The pathophysiology of these conditions is
      not widely understood; however, peripheral and central mechanisms appear to play
      a role.

PMID- 12207850
TI  - A review of the use of topical analgesics for myofascial pain.
AB  - Numerous treatment strategies for myofascial pain syndrome are available,
      including physical therapy, behavioral pain management techniques, acupuncture,
      various types of injections, and the use of various pharmacotherapeutic
      approaches. The use of topical analgesics for myofascial pain syndrome is the
      focus of this review. The use of topical analgesics in other painful states is
      also reviewed.

PMID- 12207851
TI  - Pain treatment with acupuncture for patients with fibromyalgia.
AB  - Fibromyalgia is a chronic, painful musculoskeletal syndrome of unknown
      etiopathogenesis. In addition to medicamentous and physical and psychologic
      therapies, several other adjunct therapies have been used as alternatives in the
      attempt to obtain analgesia and decrease the symptoms that are characteristic of
      this problem. This article presents a literary review on the use of acupuncture
      as an adjunct or chief treatment for patients with fibromyalgia, comparing it
      with an ongoing clinical experience that has been carried out at Hospital das
      Clinicas in the city of Sao Paulo. The results were found by applying traditional
      acupuncture, which demonstrated positive rates in the Visual Analogue Scale,
      myalgic index, number of tender points, and improvement in quality of life based
      on the SF-36 questionnaire.

PMID- 12207852
TI  - The role of temporomandibular disorders and cervical dysfunction in tension-type
      headache.
AB  - It has been estimated that 30% to 80% of the population has at least one tension
      type headache each year. Tension-type headaches can be located in any region of
      the head, which can confuse a differential diagnosis with temporomandibular joint
      disorders and cervical dysfunction. The roles of temporomandibular joint
      disorders and cervical dysfunction in tension-type headache are evaluated.
      Definitions, pathophysiology, and treatment considerations for each are
      discussed.

PMID- 12207853
TI  - Behavioral and psychologic aspects of the pathophysiology and management of
      tension-type headache.
AB  - Behavioral and psychologic factors in tension-type headache are reviewed with
      reference to pathophysiology, comorbid psychiatric disorders, headache triggers,
      and behavioral treatment, including the efficacy of behavioral treatments, brief
      minimal contact administration of behavioral treatment, therapeutic mechanisms
      underlying the effectiveness of behavioral treatments, and the integration of
      drug and behavioral treatments. Anxiety or depression may contribute to central
      sensitization that underlies frequent tension-type headaches. Excessive analgesic
      use, comorbid psychiatric disorders, or persistent unaddressed headache triggers
      may limit the effectiveness of headache treatment. Available drug and behavioral
      treatments are effective for episodic tension-type headache, but are only
      moderately effective for chronic tension-type headaches. The combination of
      behavioral and preventive drug therapies may improve outcomes for patients with
      chronic tension-type headache.

PMID- 12207854
TI  - Pharmacotherapy of tension-type headaches.
AB  - The first International Headache Society classification defined tension-type
      headaches by itemizing characteristics of migraines that tension-type headaches
      did not possess. As a result, tension-type headaches (episodic and chronic)
      remain the most nonspecific of all the commonly observed primary headaches. Until
      recently, there has been little impetus on the part of the pharmaceutical
      industry to investigate tension-type headaches; many of the potentially useful
      drugs are now generic and unprofitable. In addition, few investigators have
      pursued the study of tension-type headache because of its more glamorous
      neighbor, migraine. As a result, there are few well-designed studies on the
      pharmacotherapy of tension-type headaches. The few studies that exist support the
      use of age-old standard drug classes, the tricyclic antidepressants and the
      nonsteroidal anti-inflammatory drugs. New research is emerging that points to the
      potential use of botulinum toxin and nitric synthase inhibitors. More
      scientifically rigorous clinical studies are needed.

PMID- 12207855
TI  - Cystic Lesions of the Pancreas.
AB  - Pancreatic cystadenomas are a group of benign, premalignant, and malignant cystic
      tumors of the pancreas. Serous cystadenomas are benign lesions that often do not
      require surgical excision unless they are complicated by bleeding, obstruction,
      or pain. Mucinous cystadenomas are premalignant lesions that may be surgically
      excised if there is a concern regarding malignant degeneration. However, it may
      be difficult to predict the timing and risk of malignant change. Also, it is
      controversial whether all mucinous cystadenomas should be resected.
      Cystadenocarcinomas should be surgically managed if they are resectable, that is,
      there is no evidence of metastatic disease. Intraductal papillary mucinous tumors
      share many features with mucinous cystadenomas. However, intraductal papillary
      mucinous tumors arise from the pancreatic duct and are often associated with a
      dilated pancreatic duct. These lesions are often managed with surgical resection,
      including total pancreatectomy for diffuse lesions with evidence of localized
      malignancy.

PMID- 12207856
TI  - Pancreatic Pseudocysts.
AB  - Pseudocysts complicate acute pancreatitis in less than 5% of cases and chronic
      pancreatitis in 20% to 40% of cases. A pseudocyst is a localized collection of
      pancreatic fluid surrounded by a wall of granulation tissue and collagen. It
      takes 4 to 6 weeks for a fluid collection to mature and become a true pseudocyst.
      Unlike other cystic lesions of the pancreas from which they should be
      differentiated, pseudocysts lack an epithelial layer. Patients with pseudocysts
      present with a range of symptoms and signs. Pseudocysts are imaged using
      transabdominal ultrasound, CT, endoscopic ultrasound (EUS), and MRI. EUS confers
      an advantage over other imaging modalities in that certain EUS features are
      suggestive of pseudocysts over other cystic lesions. The diagnostic accuracy of
      EUS has improved further with the use of EUS-guided fine-needle aspiration.
      Therapeutic options include watchful observation or intervention. In our opinion,
      if acute pseudocysts are uncomplicated, asymptomatic, and do not appear to be
      enlarging on serial imaging, it is preferable to withhold intervention because
      many of these cysts resolve spontaneously. However, one needs to beware of the
      possibility of complications such as infection in unresolved pseudocysts.
      Pseudocysts associated with chronic pancreatitis are less likely to resolve
      spontaneously and are drained by intervention more frequently. Of the three
      interventional options, namely endoscopic, percutaneous, and surgical drainage,
      endoscopic drainage should be the treatment of choice if certain criteria are
      met. Preinterventional endoscopic retrograde cholangiopancreatography is
      mandatory to define ductal anatomy. If there is communication between the
      pseudocyst and the pancreatic duct, a transpapillary approach is preferred. Use
      of EUS should increase the number of cases in which pseudocysts can be drained
      endoscopically. Surgery should be reserved for cases in which there is a concern
      about malignancy or when there is glandular disruption.

PMID- 12207857
TI  - Intraductal Papillary Mucinous Neoplasm.
AB  - Surgical resection is the treatment of choice for intraductal papillary mucinous
      tumor. In intraductal papillary mucinous neoplasm, the extent of resection is
      determined by the extent of the disease. If, by pre- and intraoperative
      assessment, the disease appears localized, limited resection
      (pancreaticoduodenectomy or distal pancreatectomy) should be performed, ensuring
      that frozen sections show negative margins. Total pancreatectomy should be
      considered for extensive disease.

PMID- 12207858
TI  - Pancreatic Fistula.
AB  - External and internal pancreatic fistulas have a different etiology and natural
      history. Approximately 50% of internal and 70% to 90% of external pancreatic
      fistulas can be expected to heal with nonoperative management. Nonclosure is
      predicted by anatomic factors, which may be defined at endoscopic retrograde
      cholangiopancreatography or by CT if disconnected pancreatic segments are seen.
      Enteral nutrition beyond the ligament of Treitz is probably as effective as total
      parenteral nutrition in reducing fistula output. Octreotide reduces output and,
      possibly, time to closure. It does not increase the incidence of closure, and
      there is no convincing evidence that it prevents significant postoperative leaks.
      Endoscopic stenting has been reported to be effective treatment for side leaks,
      particularly when associated with stenoses or calculi. However, it is not widely
      available and has a significant complication rate related to pancreatic
      sphincterotomy and stent blockage. Surgical treatment is indicated for end leaks
      with a disconnected pancreatic segment. The choice of appropriate procedure is
      important. Percutaneous interventional therapies are emerging as options for
      treatment of end leaks but are still investigational.

PMID- 12207859
TI  - Gallstone Pancreatitis.
AB  - The majority of patients with acute gallstone pancreatitis have a mild attack and
      recover without additional treatment. In about 20% of patients, the attack is
      severe and is associated with a mortality rate of about 20%. Patients with severe
      pancreatitis require management in a high-dependency or intensive care setting.
      These patients are best managed in a specialized unit. Antibiotic prophylaxis is
      advised in patients with necrosis, and imipenem and cefuroxime are recommended.
      In severe pancreatitis, early enteral nutrition is recommended through a
      nasojejunal tube. In patients with severe pancreatitis or with cholangitis,
      urgent endoscopic retrograde cholangiopancreatography within 72 hours is
      indicated, and when appropriate, a sphincterotomy and clearance of the bile duct
      is performed. In sterile necrosis, conservative treatment is indicated unless the
      patient fails to improve or deteriorates, whereupon surgery is considered. If
      there is infection of pancreatic necrosis or abscess (pancreatic or
      peripancreatic), surgery is indicated. A symptomatic and persistent pancreatic
      pseudocyst requires intervention with either endoscopic drainage (transpapillary
      pancreatic stent, cystgastrostomy, or cystduodenostomy), percutaneous drainage,
      or surgery. Before discharge, patients should undergo cholecystectomy, or if they
      are unfit for surgery, endoscopic sphincterotomy and bile duct clearance.

PMID- 12207860
TI  - Treatment of Eosinophilic Esophagitis in Children.
AB  - Eosinophilic esophagitis (EE) is an important esophageal disorder with distinct
      clinicopathologic features, and the condition is associated with a high
      prevalence of food allergies and atopy. In the past decade, we have improved our
      ability to recognize the phenotype of EE, but our ability to treat EE effectively
      remains limited despite several reports of successful treatment using elemental
      or elimination diets, and systemic and topical corticosteroids. The limitations
      for developing effective treatment regimens are due to some still unresolved and
      ambiguous aspects of the pathogenesis of EE. Neither the predisposing factors for
      developing EE in a subset of patients with atopy, nor the variable responsiveness
      to control measures for allergens are fully understood. There also remain
      questions about the precise role of gastroesophageal reflux, and the natural
      history of the disorder, contingent on which is the optimal treatment of EE. In
      devising treatment for a patient with EE, all attempts should be made to identify
      and control food and other allergies. In patients who have no diagnosed allergies
      or who are unresponsive to allergy treatment, topical steroids are a safe and
      effective treatment option. Systemic steroids should be reserved for those
      patients who are refractory to topical steroids. Beyond the initial phase of
      induction treatment, it is crucial to develop effective and safe maintenance
      treatment regimens based on ongoing allergen control and mast cell inhibitors.
      There are limited but encouraging data to support further exploration of the role
      of leukotriene and interleukin-5 inhibitors as safe, effective, and steroid
      sparing treatment options.

PMID- 12207861
TI  - Treatment Options for Refractory Childhood Constipation.
AB  - Constipation in children is very common. Childhood constipation responds
      successfully to medical therapies, behavioral modifications, or a combination of
      both in approximately 70% of children within 2 years of diagnosis. Persistence of
      constipation is associated with fecal incontinence, recurrent fecal impactions,
      and significant emotional problems. Refractory constipation that interferes with
      both the child's function and the family's life requires extensive evaluations in
      order to uncover its cause and devise appropriate therapeutic strategies.
      Children with persistent constipation can be divided into three broad categories:
      1) those who have functional constipation, 2) those affected by enteric
      neuromuscular disorders, and 3) those whose constipation is associated with
      neurologic handicaps. Treatment options vary widely. The majority of patients
      require more aggressive medical and more intense behavioral interventions. Others
      benefit from novel approaches, including surgical intervention.

PMID- 12207862
TI  - Pouchitis in Children: Therapeutic Options.
AB  - Pouchitis is an unfortunate common complication of the ileal pouch-anal
      anastomosis procedure, an otherwise very attractive surgical option in patients
      with ulcerative colitis (UC). The fact that the same pouch in familial polyposis
      is hardly complicated by pouchitis suggests that the basic inflammatory process
      in UC might participate in the pathophysiology. We review the clinical features
      of pouchitis, the diagnostic approach, and the many therapeutic considerations,
      including more recent data on prebiotics and probiotics.

PMID- 12207863
TI  - Management of Gastrointestinal Bleeding in Children.
AB  - Gastrointestinal bleeding in infants and children is a potentially life
      threatening problem that is encountered by virtually all practicing pediatric
      gastroenterologists. Youngsters with a normal hematocrit, hemodynamic stability,
      and a history consistent with an acute, self-limited illness most frequently need
      only close observation; others require more in-depth assessment and intervention.
      Meticulous attention to the patient's cardiopulmonary status and knowledge of
      appropriate pediatric resuscitation schemes form the cornerstones on which more
      specific therapeutic interventions are based. Many treatment techniques and
      approaches have been extrapolated for pediatric use from adult studies; the
      regimen implemented for a child should be individualized and based on factors
      such as patient size, underlying condition, and operator expertise. Although the
      physician treating pediatric gastrointestinal hemorrhage requires more than a
      modicum of patience and determination, this must be tempered with a ready
      willingness to seek consultation from surgical colleagues to ensure optimal
      outcomes. Knowledge of acid-suppressive and vasoactive medications is essential,
      as is familiarity with at least one injection technique and one thermocoagulation
      technique for hemostasis. Endoscopic sclerotherapy and variceal band ligation are
      equally efficacious in achieving control of acute variceal bleeding, but band
      ligation is emerging as the technique best suited for prophylaxis. Beta blockade
      appears to have a smaller and less well-defined role in pediatric variceal
      prophylaxis compared with that in adults, but random controlled trials are
      necessary to confirm this impression.

PMID- 12207864
TI  - Effect of the solvent system on the in vitro permeability of nicardipine
      hydrochloride through excised rat epidermis.
AB  - PURPOSE: The present investigation was carried out to study the effect of the
      solvent system on the permeation of nicardipine hydrochloride across excised rat
      epidermis in order to select a suitable solvent system for use in the development
      of a transdermal therapeutic system. METHODS: The solubility of nicardipine
      hydrochloride in pure and mixed solvent systems was determined. The solvents used
      were water, propylene glycol, ethanol or various proportions of ethanol and
      water. The effect of these pure or mixed solvent systems on the skin permeation
      of nicardipine hydrochloride was also studied using in vitro permeation studies
      through excised rat epidermis mounted in modified Keshary-Chien diffusion cells.
      Fourier Transform Infrared Spectroscopy (FT-IR) and Differential Scanning
      Calorimetry (DSC) studies were carried out to study the effect of these solvents
      on the biophysical properties of rat' stratum corneum. RESULTS: Although the
      solubility of nicardipine hydrochloride in propylene glycol (51.23 mg/mL) was
      higher than that in water (7.90 mg/mL) and ethanol (20.01 mg/mL), the flux of the
      drug from propylene glycol was as low (7.25+/-0.13 microg/cm(2)/h) as that from
      water (7.05+/-0.15 microg/cm(2)/h) and lower than that from ethanol (21.51+/-0.81
      microg/cm(2)/h). The solubility of nicardipine hydrochloride in binary ethanol
      water solvent systems in various proportions was higher than in pure solvents.
      The highest permeability was observed from an ethanol-water (70:30 v/v) solvent
      system (56.10+/-1.23 micro g/cm(2)/h) which showed the highest solubility (224.21
      mg/mL). The DSC and FT-IR data indicated that the binary solvent system
      containing ethanol-water in the ratio of 70:30 v/v increased the drug
      permeability through the skin by disrupting the highly ordered intercellular
      lipid structure of the stratum corneum in comparison with the untreated stratum
      corneum. CONCLUSIONS: The results of the study indicate that the use of a binary
      solvent system, ethanol and water in the ratio of 70:30 v/v, is an effective
      vehicle for the development of a transdermal therapeutic system for nicardipine
      hydrochloride.

PMID- 12207865
TI  - A quantitative thin layer chromatography method for determination of theophylline
      in plasma.
AB  - A simple assay method for theophylline in plasma using thin layer chromatography
      (TLC) was developed. The method involves extraction of the drug and internal
      standard (acetaminophen) by chloroform-isopropanol (75:25) followed by separation
      on TLC silica plates using a mixture of acetic acid, isopropanol, toluene (1: 12:
      6), as the eluting solvent. Both peak height ratios and peak are ratios showed
      high correlation coefficient (r>0.98, p<0.001). However we used peak heights for
      the determinations. Within-day and between-day coefficients of variation were
      less than 4.4% and 7.8% respectively. The assay proved inexpensive, accurate and
      reproducible with a limit of detection of 100 ng/ml that makes it suitable for
      bioavailability studies.

PMID- 12207866
TI  - A novel HPLC assay for pentamidine: comparative effects of creatinine and inulin
      on GFR estimation and pentamidine renal excretion in the isolated perfused rat
      kidney.
AB  - PURPOSE: 1. To develop and validate an analytical method for pentamidine (PTM) by
      reversed-phase HPLC. 2. To compare the effects of creatinine and inulin on PTM
      excretion in the isolated perfused rat kidney. METHODS: The HPLC method utilized
      a base deactivated, 5 micro, C18 column and a mobile phase containing
      acetonitrile (24%) and 0.025 M monobasic phosphate buffer, pH 3.2 (76%). Mobile
      phase flow rate and UV detection wavelength were 1 mL/min and 270 nm,
      respectively. Sulfadiazine (SDZ) was used as the internal standard. The method
      was used to measure pentamidine in perfusate and urine samples generated from
      studies with the isolated perfused rat kidney (IPK) model. Perfusion experiments
      were conducted in the presence of two different GFR markers: creatinine and
      inulin (PTM dose 800 micro g). Both creatinine and inulin were assayed using
      colorimetric methods. RESULTS: The HPLC assay is rapid, sensitive and
      reproducible. The method was validated over two standard concentration ranges:
      0.1 to 1 micro g/mL, and 1 to 10 micro g/mL. In control (drug-naive) IPK
      perfusions, creatinine clearance was approximately 15% greater than inulin
      clearance (0.80+/- 0.21 mL/min vs. 0.69+/-0.17 mL/min, p > 0.05). In the presence
      of PTM, however, creatinine clearance was reduced to 0.56+/-0.27 (p < 0.05
      compared to control). Inulin clearance was not altered by PTM administration
      (0.76+/-0.26 mL/min). Cumulative urinary excretion of PTM (% dose) was 3.0+/
      0.47% and 9.6+/-4.2% in the presence of creatinine and inulin, respectively. PTM
      clearance was significantly reduced (0.06+/-0.01 mL/min vs. 0.13+/-0.01 mL/min, p
      < 0.05) and % kidney accumulation significantly enhanced (66+/-4.7% vs. 37+/
      9.7%, p < 0.05) by creatinine. CONCLUSIONS: Creatinine overestimated GFR in the
      IPK. The altered renal excretion of PTM by creatinine is consistent with
      inhibition of PTM tubular secretion. Because of increased kidney accumulation,
      detrimental effects of PTM on renal function were observed. Based on these
      findings, creatinine should be used cautiously as an indicator of GFR in IPK
      experimentation.

PMID- 12207867
TI  - Role of integrative pharmacokinetic and pharmacodynamic optimization strategy in
      the management of Parkinson"s disease patients experiencing motor fluctuations
      with levodopa.
AB  - Parkinson's disease is a progressively debilitating motor neuron disease that
      affects the dopaminergic neurons within the nigral-striatal and surrounding
      pathways and which is characterized clinically by rigidity, resting tremor and
      bradykinesia with or without postural imbalance. Levodopa is the "gold standard"
      for the treatment and management of Parkinson's disease worldwide. However,
      following prolonged use of the drug, the "honey-moon" which was once enjoyed by
      patients on levodopa begins to wane. The clinical as well as the socio-economic
      costs associated with such failure in response to levodopa is enormous. Various
      approaches in the management of Parkinson's disease patients experiencing motor
      fluctuations with levodopa treatment have been suggested and include both
      pharmacologic and non-pharmacologic strategies involving invasive surgical
      intervention. Currently, the non-pharmacological approach, which is invasive,
      remains to be fully perfected and is associated with high morbidity and
      mortality. The use of the non-invasive, pharmacological approach is currently the
      most widely accepted approach but would require a review of all possible drug
      regimens used. This entails evaluating the pharmacokinetics and pharmacodynamic
      actions of the drug regimens used and possibly, dosage form and route of
      administration of the drugs. The use of levodopa formulated for transdermal or
      intranasal administration might help improve the ease of use and compliance.
      Controversy abounds as to the role of plasma pharmacokinetics of levodopa in the
      management of Parkinson's patients, vis a vis its dynamics at the central nerve
      terminal and its receptor site. However, it is worthy of mention that an
      integrated optimal pharmacological approach involving the peripheral, and central
      pharmacokinetics of levodopa as well as its central pharmacodynamics would ensure
      better treatment and management of this disease. In addition, the choice of
      alternate formulations and routes of administration will not only improve on the
      bioavailability and overall pharmacokinetics of levodopa, but also increase
      compliance. Furthermore, monitoring of both plasma and central concentrations of
      levodopa and its metabolites might play a major role in individualization of
      pharmacotherapy in special Parkinsonian patients experiencing motor fluctuations
      with levodopa.

PMID- 12207868
TI  - Effect of powder polydispersity on aerosol generation.
AB  - PURPOSE: We investigated the effect of primary powder polydispersity on the
      generation of pharmaceutical powder aerosols, using mannitol and bovine serum
      albumin (BSA) as the model compounds. METHODS: Primary powders with different
      polydispersity but comparable physical and mass median aerodynamic diameter
      (MMAD) were obtained from spray drying. The polydispersity, i.e. the width of the
      particle size distribution, of the primary powder was measured by the span. Span
      = [particle diameter at 90% cumulative size] - [particle diameter at 10%
      cumulative size] / [particle diameter at 50% cumulative size]. A small span
      indicates a narrow size distribution. Solid state properties and the aerosol
      behaviour of the powders were determined. RESULTS: For both compounds, dispersion
      of the smaller span powder generated more fine particles below the MMAD of the
      primary powder, but the increase was less apparent at high air flows or with a
      high dispersion efficiency inhaler. With the Dinkihaler, however, the smaller
      span powder of BSA, but not of mannitol, was found to experience less impaction
      loss and capsule and device retention. This could be due to the BSA powder being
      more cohesive, as it was amorphous and had a higher residual moisture content
      than that of mannitol. CONCLUSIONS: The present study has demonstrated that the
      amount of fines available in the aerosol could be modified by the primary powder
      polydispersity.

PMID- 12207869
TI  - Reanalysis of carbamazepine and carbamazepine-epoxide pharmacokinetics after
      multiple dosing of extended release formulation.
AB  - PURPOSE: To model and re-evaluate the pharmacokinetics of carbamazepine (CBZ) and
      CBZ-10, 11-epoxide (CBZ-E) after 5 day b.i.d. dosing with either Carbatrol
      (extended-release beads) or Tegretol-XR (an osmotic pump tablet, an Oros tablet)
      using compartmental method. METHODS: Plasma concentration time profile data from
      15 normal healthy adults received, in a randomized crossover fashion, Carbatrol
      (2 x 200 mg capsules), b.i.d. for 5 days and Tegretol-XR (400 mg), b.i.d. for 5
      days were available for analysis from previous study. The compartmental kinetic
      parameters of CBZ and CBZ-E were simultaneously fitted by assuming: i) one
      compartment open model with zero order absorption with lag time, and first order
      elimination for CBZ and ii) one compartment open model with Michaelis-Menten
      formation with a sigmoidity factor, and first order elimination for CBZ-E. Time
      to 50% of CBZ plateau concentrations (TC50) was estimated and statistically
      compared between the two products. RESULTS: There was a good agreement between
      simulated and observed plasma concentrations. For CBZ, the fitted parameters
      were: the first order elimination rate constant (K(10)) 0.024 and 0.022 hr(-1),
      t(1/2) 27.3 and 30.3 hr, volume of central compartment (V(1) ) 1.119 and 1.160
      L/kg, for Carbatrol and Tegretol-XR, respectively. For CBZ-E, the fitted
      parameters were: the first order elimination rate constant (K (30) ) 0.128 and
      0.157 hr (-1), t (1/2) 6.1 and 5.1 hr, volume of central compartment (V (3) )
      0.728 and 0.644 L/kg, V (max) 0.085 and 0.076 mg/hr/kg, K (m) 28.639 and 33.138
      mg/mL, for Carbatrol and Tegretol-XR, respectively. The fitted pharmacokinetic
      parameters of CBZ and CBZ-E were generally consistent with published values from
      previous studies. A minimal rise in CBZ-E concentrations was observed during the
      first 12 hours, the finding of which has not been reported before. Consequently,
      the CBZ-E plasma profiles appear as sigmoid curves and have a different shape
      compared to those of the CBZ profiles. The inclusion of the sigmoidity factor
      allowed flexibility in the fitting and optimized the simulation results. When
      compared to published literature of single dose data, the investigation of CBZ
      and CBZ-E pharmacokinetics from this study suggested that autoinduction might
      occur by the fifth day of dosing and might partly contribute to the sigmoidal
      shape of CBZ-E profiles. CONCLUSION: The fitted model well described the plasma
      profiles of both CBZ and CBZ-E. Carbatrol and Tegretol-XR were similar in their
      pharmacokinetics based on compartmental analysis.

PMID- 12207870
TI  - High performance liquid chromatographic determination of glucosamine in rat
      plasma.
AB  - PURPOSE: A high performance liquid chromatographic method was developed for the
      determination of glucosamine (GlcN) in rat plasma. METHOD: Internal standard,
      galactosamine, was added to 100 micro L of plasma containing GlcN followed by
      precipitation of plasma proteins with acetonitrile. Evaporation of the decanted
      supernatant solution was accelerated by the addition of methanol. GlcN was
      derivatized by addition of a solution containing 1-naphthyl isothiocyanate.
      Sample cleanup included passage through an anion exchange cartridge. Analysis was
      accomplished by injection of 0.1 mL of the sample solution into an isocratic HPLC
      system consisting of a C18 column, a mobile phase of acetonitrile: water: acetic
      acid: triethylamine (4.5: 95.5:0.1:0.05), a flow rate of 0.9 mL/min, and a UV
      detector set at 254 nm. RESULTS: Galactosamine and GlcN appeared 26 and 29 min
      post-injection, respectively. The assay was linear over the range of 1.25-400
      micro g/mL (CV<10%) with a detection limit of 0.63 microg/mL and a limit of
      quantification of 1.25 microg/mL. The method was applied to the determination of
      GlcN in rat plasma after oral administration of 350 mg/kg of GlcN hydrochloride.
      CONCLUSION: The present assay is specific, sensitive, precise, and accurate and
      is suitable for pharmacokinetic studies.

PMID- 12207871
TI  - Single dose pharmacokinetics and bioavailability of glucosamine in the rat.
AB  - PURPOSE: To study pharmacokinetics of glucosamine following various routes of
      administration of the hydrochloride salt to rats and locate the site of its first
      pass metabolism. METHODS: Rat were cannulated in the jugular vein and single
      intravenous, oral and intra peritoneal doses of 350 mg/kg were administered.
      Serial blood samples were collected and plasma glucosamine concentrations were
      determined using HPLC. RESULTS: After intravenous administration, the apparent
      terminal half-life (1.09 +/- 0.98 h), apparent steady state volume of
      distribution (2.1 +/- 1.1 L.kg(-1)) and total body clearance (2.61 +/- 0.81 L.kg(
      1.h-1)) were calculated. The peak plasma concentration, after oral
      administration, occurred approximately 30 min post-dose and the absolute
      bioavailability was 0.19. Glucosamine was completely bioavailable after
      intraperitoneal administration. CONCLUSION: Orally administered glucosamine is
      rapidly absorbed, highly distributed and efficiently cleared. The gut rather than
      liver is mainly responsible for the first pass metabolism since reduced
      bioavailability is observed after oral but not intraperitoneal doses.

PMID- 12207873
TI  - Statistical analysis of tablet breakability methods.
AB  - PURPOSE: Using a model tablet, the influence of breakability methodology on mass
      uniformity of half- and quarter-tablets as well as the comparison of different
      data acquisition and evaluation approaches were investigated. Moreover, different
      breakability evaluation criteria were compared based upon distribution as well as
      distribution-free models. METHODS: A cross-scored tablet, i.e. having two break
      marks, was broken by different methods by different persons, and the masses
      determined for the whole (unbroken) tablets, the half-tablets and quarter
      tablets. RESULTS: Beside the possible interaction between the methodology and the
      person breaking the tablets, the major factor significantly influencing the mass
      uniformity of broken tablets is the breakability methodology. The best results,
      i.e. smallest loss and smallest variability, are obtained when the breaking force
      applied by the thumbs is directed towards the score side of the tablet, i.e. by
      "opening" the score. Using our model tablet, significant differences between the
      different evaluation criteria are observed, with the USP/NF approach being best
      in line with the detailed analysis of all broken tablets. CONCLUSIONS: Assuming
      that for this model tablet the variance is a linear function of the break-line
      length, the standard deviation of quarter-tablets is theoretically calculated to
      be 0.87 times the standard deviation of the half-tablets. As the absolute
      standard deviation, expressed in mass units, will thus remain approximately
      identical, the relative standard deviation will nearly double as the mean mass of
      the quarter-tablets will be half of the mean mass of the half-tablets. This was
      experimentally confirmed.

PMID- 12207872
TI  - Effect of several Chinese natural health products of human cytochrome P450
      metabolism.
AB  - PURPOSE: Traditional Chinese medicines (TCM) are believed by many to be safe and
      used for self-medication without supervision. Although the risk appears to be
      low, certain TCM have been associated with a number of serious adverse reactions.
      A preliminary study was undertaken with 12 products using a human cytochrome P450
      (CYP450) isozyme assay to determine if these products could affect human drug
      metabolism. METHODS: Aliquots of samples were analyzed directly or as extracts
      for their potential to affect CYP450 2C9, 2C19, 2D6, and 3A4 mediated-metabolism
      of marker substrates using an in vitro fluorometric microtiter plate assay.
      RESULTS: One product was found to be a Chinese Proprietary Medicine (CPM). Most
      aqueous extracts inhibited CYP450 mediated-metabolism of at least 3 isozymes
      (ranging from 25-100%). All liquid samples markedly inhibited the metabolism of
      all 4 isozymes. De le ke chuan kang and Rensheng dao were the strongest CYP450
      inhibitors. CONCLUSIONS: Our in vitro findings demonstrate that TCM can inhibit
      CYP450 2C9, 2C19, 2D6 and 3A4 mediated-metabolism. TCM need to be examined
      further under clinical settings to determine if potential interactions will occur
      that affect the safety and efficacy of conventional therapeutic products.

PMID- 12207874
TI  - Comparative efficacy and pharmacokinetics of racemic bupivacaine and S
      bupivacaine in third molar surgery.
AB  - PURPOSE: To compare the efficacy and pharmacokinetics of racemic bupivacaine (rac
      bupivacaine) with S-bupivacaine as primary local anesthetic agent in bilateral
      impacted third molar extractions. METHOD: A randomised, double blind, two period
      cross-over design was employed. Six subjects (2 males, 4 females; age 19-25
      years; weight 69.2+/-9.4 kg) received bupivacaine hydrochloride injection (6.6
      ml) as rac-bupivacaine (0.5% as salt) or S-bupivacaine (0.5% as base) prior to
      extraction of impacted third molars on one side and three weeks later on the
      other side. Anesthesia, blood loss associated with surgery and post-operative
      pain experience were evaluated. Plasma samples were analysed for bupivacaine
      enantiomers by chiral HPLC. RESULTS: In 7/12 operations, anesthesia adequate for
      surgery was delayed (>10 min) or unsatisfactory requiring lidocaine rescue
      medication. Despite this, there were no significant differences in onset and
      duration of anesthesia, blood loss or post-operative pain experience between the
      two arms of the study. Pharmacokinetic parameters were not significantly
      different and there was no evidence of chiral inversion after dosing with S
      bupivacaine. CONCLUSIONS: Both study drugs were inadequate as single anesthetic
      agent for third molar surgery. Any decision to use S-bupivacaine for oral surgery
      must rest on evidence that it is less toxic than the racemic drug.

PMID- 12207875
TI  - Serendipitous discoveries from sudden inspirations and the joy of being a
      scientist.

PMID- 12207876
TI  - Regeneration therapy of pancreatic beta cells: towards a cure for diabetes?
AB  - Regeneration therapy is an approach which could potentially move us towards a
      cure for type 1 diabetes. It is classified into three categories: (1) In vitro
      regeneration therapy using transplanted cultured cells, including ES cells,
      pancreatic stem cells, and beta-cell lines, in conjunction with immunosuppressive
      therapy or immunoisolation. (2) In ex vivo regeneration therapy, patients' own
      cells, such as bone marrow stem cells, are transiently removed and induced to
      differentiate into beta cells in vitro. At present, however, insulin-producing
      cells cannot be generated from bone marrow stem cells. (3) In in vivo
      regeneration therapy, impaired tissues regenerate from patients' own cells in
      vivo. beta-Cell neogenesis from non-beta-cells and beta-cell proliferation in
      vivo have been considered, particularly as regeneration therapies for type 2
      diabetes. Regeneration therapy of pancreatic beta cells can be combined with
      various other therapeutic strategies, including islet transplantation, cell-based
      therapy, gene therapy, and drug therapy to promote beta-cell proliferation and
      neogenesis, and it is hoped that these strategies will, in the future, provide a
      cure for diabetes.

PMID- 12207877
TI  - Conformation-dependent antibiotic activity of tritrpticin, a cathelicidin-derived
      antimicrobial peptide.
AB  - Tritrpticin, a Trp-rich cationic antimicrobial peptide with a unique amino acid
      sequence (VRRFPWWWPFLRR), is found in porcine cathelicidin cDNA. Tritrpticin has
      a broad spectrum of antibacterial and antifungal activities and hemolytic
      activity comparable to that of indolicidin. To investigate the mechanism of the
      bacterial killing action of tritrpticin and to identify structural features
      important for bacterial cell selectivity, we designed several tritrpticin analogs
      with amino acid substitutions of the Pro and Trp residues. Circular dichroism
      studies revealed that the substitution of Pro-->Ala (TPA) or Trp-->Phe (TWF)
      leads to significant conformational changes in SDS micelles, converting the beta
      turn to alpha-helix or to poly-L-proline II helix, respectively. Compared to
      tritrpticin, TPA retained most of its antimicrobial activity, but showed enhanced
      hemolytic and membrane-disrupting activities. In contrast, TWF showed a 2-4-fold
      increase in antimicrobial activity against Gram-negative bacteria, but a marked
      decrease in both hemolytic and membrane-disrupting activities. Taken together,
      our findings suggest that compared with the beta-turn and alpha-helical
      structures, the poly-L-proline II helix is crucial for effective bacterial cell
      selectivity in tritrpticin and its analogs.

PMID- 12207878
TI  - Testosterone up-regulates scavenger receptor BI and stimulates cholesterol efflux
      from macrophages.
AB  - By lowering high density lipoprotein (HDL) cholesterol, testosterone contributes
      to the gender difference in HDL cholesterol and has been accused to be pro
      atherogenic. The mechanism by which testosterone influences HDL cholesterol is
      little understood. We therefore investigated the effect of testosterone on the
      gene expression of apolipoprotein A-I (apoA-I), hepatic lipase (HL), scavenger
      receptor B1 (SR-BI), and the ATP binding cassette transporter A1 (ABCA1), all of
      which are important regulators of HDL metabolism. In both cultivated HepG2
      hepatocytes and primary human monocyte-derived macrophages, testosterone led to a
      dose-dependent up-regulation of SR-BI, which was assessed on both the mRNA and
      the protein levels. As a functional consequence, we observed an increased HDL(3)
      induced cholesterol efflux from macrophages. At supraphysiological dosages,
      testosterone also increased the expression of HL in HepG2 cells. Testosterone had
      no effect on the expression of apoA-I in HepG2 cells and ABCA1 in either HepG2
      cells or macrophages. These data suggest that testosterone, despite lowering HDL
      cholesterol, intensifies reverse cholesterol transport and thereby exerts an anti
      atherogenic rather than a pro-atherogenic effect.

PMID- 12207879
TI  - Gln277 and Phe554 residues are involved in thermal inactivation of protective
      antigen of Bacillus anthracis.
AB  - Protective antigen (PA) is the main component of all the vaccines against
      anthrax. The currently available vaccines have traces of other proteins that
      contribute to its reactogenicity. Thus, purified PA is recommended for human
      vaccination. PA loses its biological activity within 48h at 37 degrees C and its
      thermolability has been a cause of concern as accidental exposure to higher
      temperatures during transportation or storage could decrease its efficacy. In the
      present study, we have used protein engineering approach to increase the
      thermostability of PA by mutating amino acid residues on the surface as well as
      the interior of the protein. After screening several mutants, the mutants
      Gln277Ala and Phe554Ala have been found to be more thermostable than the wild
      type PA. Gln277Ala retains approximately 45% and Phe554Ala retains approximately
      90% activity, even after incubation at 37 degrees C for 48h while in the same
      period wild-type PA loses its biological activity completely. It is the first
      report of increasing thermostability of PA using site-directed mutagenesis.
      Generation of such mutants could pave the way for better anthrax vaccines with
      longer shelf life.

PMID- 12207880
TI  - Salinity- and ABA-induced up-regulation and light-mediated modulation of mRNA
      encoding glycine-rich RNA-binding protein from Sorghum bicolor.
AB  - Glycine-rich RNA-binding proteins play an important role in post-transcriptional
      regulation of gene expression, including RNA processing, and are known to be up
      regulated in response to a number of external stimuli. However, their regulation
      in response to salinity stress has not been reported. We have isolated a light-
      and salt-regulated, full-length cDNA clone encoding a putative glycine-rich
      protein containing conserved ribonucleoprotein motif from Sorghum bicolor
      designated as sbGR-RNP. Sequence analysis of the 701bp insert revealed that the
      open reading frame of 513bp encodes a 170 amino acid protein, with an apparent
      molecular mass of 16.68kDa and calculated pI of 6.59. The deduced amino acid
      sequence also revealed that protein is hydrophilic in nature and contains 38%
      glycine residues. Northern blot analysis revealed a transcript size of 630
      nucleotides, which shows regulation by blue and red light. The transcript is
      initially up- and down-regulated rapidly within 5min of irradiation with blue and
      red light, respectively. This kind of rapid and opposite regulation by different
      light wavelengths could be a novel behavior of this photo-regulated gene.
      Furthermore, NaCl (500mM) and abscisic acid (10 microM) also stimulated the
      transcript levels of sbGR-RNP to fourfold and sevenfold, respectively. These
      novel regulations of sbGR-RNP in response to light and salinity are important
      phenomena, which will be helpful in understanding the molecular mechanisms of
      cross-talk between abiotic stress and light signaling in plants.

PMID- 12207881
TI  - Novel optical solid-state glucose sensor using immobilized glucose oxidase.
AB  - Meso-tetra(4-carboxyphenyl)porphine (CTPP(4)) binds reversibly to immobilized
      glucose oxidase (GOD), resulting in an absorbance peak for the CTPP(4)-GOD
      complex at 427nm. The absorbance intensity of the 427nm peak is reduced upon
      exposure to glucose, which causes the dissociation of CTPP(4) from GOD. The
      change in absorbance at 427nm shows linear dependence on glucose concentration
      from 20 to 200mg/dL (1.1-11.1mM).

PMID- 12207882
TI  - Generation of thermostable monomeric luciferases from Photorhabdus luminescens.
AB  - Bacterial luciferases and the genes encoding these light-emitting enzymes have an
      increasing number of applications in biological sciences. Temperature lability
      and the heterodimeric nature of these luciferases have been the major obstacles
      for their widespread use, for instance, as genetic reporters. Escherichia coli
      expressing wild-type Photorhabdus luminescens luciferase was found to produce
      eight times more light than the corresponding Vibrio harveyi luciferase clone in
      vivo at 37 degrees C. Three monomeric luciferases were created by translationally
      fusing the two genes encoding luxA and luxB proteins of P. luminescens. These
      clones were equally active in producing light in vivo when cultivated at 37
      degrees C compared to cultivation at 30 degrees C. The fusion containing the
      longest linker showed the highest activity. In vitro, the monomeric luciferases
      were less active having at best 20% of activity of the wild-type enzyme due to
      the partial formation of insoluble aggregates. The results suggest that P.
      luminescens luciferase and monomeric derivatives thereof should be more suitable
      than the corresponding V. harveyi enzyme to be used as reporters in cell types
      which need cultivation at elevated temperatures.

PMID- 12207883
TI  - Differential effect of heme oxygenase-1 in endothelial and smooth muscle cell
      cycle progression.
AB  - Arterial remodeling in response to pathological insult is a complex process that
      depends in part on the balance between vascular cell apoptosis and proliferation.
      Studies in experimental models suggest that HO-1 mediates neointimal formation
      while limiting lumen stenosing, indicating a differential effect on vascular
      endothelial (EC) and smooth muscle cells (SMC). We investigated the effect of HO
      1 expression on cell cycle progression in EC and SMC. The addition of SnMP (10
      microM), an inhibitor of HO activity, to EC or SMC for 24h, resulted in
      significant abnormalities in DNA distribution and cell cycle progression compared
      to cells treated with the HO-1 inducers, heme (10 microM) or SnCl(2) (10 microM).
      SnMP increased G(1) phase and decreased S and G(2)/M phases in EC while heme or
      SnCl(2) decreased G(1) phase, but increased S and G(2)/M phases (p<0.05).
      Opposite effects were obtained in SMC. SnMP decreased G(1) phase and increased S
      and G(2)/M phases while heme or SnCl(2) increased G(1) phase but decreased S and
      G(2)/M phases (p<0.05). Our data demonstrate that HO-1 regulates the cell cycle
      in a cell-specific manner; it increases EC but decreases SMC cycle progression.
      The mechanisms underlying the HO-1 cell-specific effect on cell cycle progression
      within the vascular wall are yet to be explored. Nevertheless, these findings
      suggest that cell-specific targeting of HO-1 expression may provide a novel
      therapeutic strategy for the treatment of cardiovascular diseases.

PMID- 12207884
TI  - Identification of nuclear type II [(3)H]estradiol binding sites as histone H4.
AB  - [3H]Luteolin binds covalently to uterine nuclear type II sites [B. Markaverich,
      K. Shoulars, M.A. Alejandro, T. Brown, Steroids 66 (2001) 707] and was used to
      identify this protein(s). SDS-PAGE analyses of [3H]luteolin-labeled type II site
      preparations revealed specific binding to 11- and 35-kDa proteins. The 11-kDa
      protein was identified as histone H4 by amino acid sequencing. Western blotting
      confirmed that the 11- and 35-kDa proteins were acetylated forms of histone H4.
      Anti-histone H4 antibodies (but not H2A, H2B, or H3 antibodies) quantitatively
      immunoadsorbed type II binding sites from nuclear extracts. Binding analyses by
      [3H]estradiol exchange, using luteolin as a competitor, detected specific type II
      binding activity to histone H4 (but not histones H2A, H2B, or H3) generated in a
      rabbit reticulocyte lysate translation system and confirmed that histone H4 is
      the type II site.

PMID- 12207885
TI  - Casein kinase II stimulates rat liver mitochondrial glycerophosphate
      acyltransferase activity.
AB  - Rat liver mitochondrial glycerophosphate acyltransferase (mtGAT) possesses 14
      consensus sites for casein kinase II (CKII) phosphorylation. To study the
      functional relevance of phosphorylation to the activity of mtGAT, we treated
      isolated rat liver mitochondria with CKII and found that CKII stimulated mtGAT
      activity approximately 2-fold. Protein phosphatase-lambda treatment reversed the
      stimulation of mtGAT by CKII. Labeling of both solubilized and non-solubilized
      mitochondria with CKII and [gamma-32P]ATP resulted in a 32P-labeled protein of
      85kDa, the molecular weight of mtGAT. Our findings suggest that CKII stimulates
      mtGAT activity by phosphorylation of the acyltransferase. The significance of
      this observation with respect to hormonal control of the enzyme is discussed.

PMID- 12207886
TI  - TBP-interacting protein 120B, which is induced in relation to myogenesis, binds
      to NOT3.
AB  - TBP-interacting protein 120 (TIP120) has been identified by TBP-mediated affinity
      screening. Classical TIP120, TIP120A, which functions as a transcriptional
      activator, is expressed ubiquitously whereas TIP120B is specifically expressed in
      muscle tissues. We found that TIP120B gene was induced in C2C12 myoblasts when
      these cells differentiated into myotubes, whereas TIP120A gene expression was
      down-regulated. Whole-mount in situ hybridization revealed that TIP120B mRNA was
      concentrated in limb buds of mouse embryos. TIP120B is thus thought to be a
      myogenesis-responding gene. We searched for TIP120B-binding proteins by yeast two
      hybrid screening and identified NOT3. NOT3, a constituent of CCR4-NOT complex, is
      suggested to be involved in global gene regulation via interaction with TBP. The
      human NOT3 (hNOT3L), which we identified, has an extra 144 amino acids (AAs) at
      the C-terminus of a classical NOT3. GST pull-down and yeast two-hybrid assays
      demonstrated that hNOT3L is associated with TIP120B but not with TIP120A. A
      hNOT3L-specific C-terminal region of 92 AAs was assigned as a TIP120B-interacting
      domain. The N-terminus of 209 AAs of TIP120B was responsible for this binding.
      TIP120B presumably affects tissue-specific transcriptional regulation via
      interaction with NOT3.

PMID- 12207887
TI  - VCY2 protein interacts with the HECT domain of ubiquitin-protein ligase E3A.
AB  - VCY2 locates in the AZFc region on chromosome Yq and is frequently deleted in
      infertile men with severe oligozoospermia or azoospermia. VCY2 is a testis
      specific protein with unknown function. This study was to identify the protein
      that interacts with VCY2. We used the full-length VCY2 as bait to screen the
      human testis cDNA library using yeast two-hybrid approach. We identified a number
      of positive-interacting clones that encode ubiquitin-protein ligase E3A (UBE3A).
      UBE3A contains a HECT domain that binds VCY2. The specificity of the interaction
      was confirmed by co-immunoprecipitation and yeast mating. Northern blot analyses
      revealed two UBE3A transcripts 1.4 and 2kb that were abundantly expressed in
      human testis. We also showed that both VCY2 and UBE3A mRNAs were expressed in
      ejaculated human spermatozoa, indicating that both genes localize in the germ
      cell compartment. These data suggest that UBE3A ubiquitination may be required
      for VCY2 function.

PMID- 12207888
TI  - Isolation and identification of the AKH III precursor-related peptide from
      Locusta migratoria.
AB  - We have isolated an 8770Da peptide from extracts of corpora cardiaca of adult
      male and female Locusta migratoria. The N-terminal amino-acid sequence as
      partially established by Edman degradation is Ala-Leu-Gly-Ala-Pro-Ala-Ala-Gly
      Asp. These nine amino acids correspond to the first nine N-terminal amino acids
      of the adipokinetic hormone precursor-related peptide gamma-chain (APRP-gamma), a
      peptide that is predicted from the gene encoding the adipokinetic hormone III
      precursor. The APRP-gamma chain has a monoisotopic mass of 4387Da and contains
      two cysteine residues. It is known that both AKH I and AKH II precursors occur as
      dimers. After processing they give rise to the active hormones and three dimeric
      (two homodimers and one heterodimer) adipokinetic hormone precursor related
      peptides (APRPs). Based on the mass of 8770Da and the established N-terminal
      sequence tag, we conclude that the isolated peptide is a homodimer consisting of
      two APRP-gamma units, covalently linked to each other by two disulphide bounds.
      In analogy with the previous identified APRPs (APRP-1, APRP-2, and APRP-3), this
      APRP will be designated as APRP-4.

PMID- 12207889
TI  - Phylogeny of New World arenaviruses based on the complete coding sequences of the
      small genomic segment identified an evolutionary lineage produced by
      intrasegmental recombination.
AB  - Previous studies suggested that the small genomic segments (S-RNA) of the South
      American arenaviruses (SA-AVs) represent three phylogenetic lineages (designated
      A, B, and C) and indicated that the S-RNA of Whitewater Arroyo virus (WWAV) (a
      North American arenavirus [NA-AV]) is a product of genetic recombination between
      a lineage A and lineage B virus. The purpose of this study was to extend our
      knowledge on the phylogenetic relationships between WWAV, the two other NA-AVs
      (Tamiami and bear canyon), and the 15 SA-AVs. Therefore, we determined the
      complete sequence of the S-RNA of nine arenaviruses previously uncharacterized or
      sequenced only partially. Phylogenetic analyses of the two complete coding
      regions indicated that the S-RNA of the three NA-AVs have descended from a single
      ancestral virus, which was the product of recombination between a lineage A and
      lineage B arenavirus. No such evidence for genetic recombination was found in
      cupixi virus (a novel arenavirus isolated from a wild rodent captured in
      Northeastern Brazil) or the 14 other SA-AVs. The recombinant nature of the S-RNA
      of NA-AVs distinguishes them from the SA-AVs, and thus, indicates that the NA-AVs
      represent a fourth phylogenetic lineage in the Tacaribe serocomplex.

PMID- 12207891
TI  - Construction of a zebrafish cDNA microarray: gene expression profiling of the
      zebrafish during development.
AB  - Vertebrate embryogenesis is a complex process controlled by a transcriptional
      hierarchy that coordinates the action of thousands of genes. To identify and
      analyze the expression patterns of these genes, we constructed a zebrafish cDNA
      microarray containing 4512 unique genes identified from zebrafish embryonic
      heart, adult hearts, and skeletal muscle cDNA libraries. We examined the patterns
      of gene expression during development in the zebrafish between five time points
      relative to 12h post-fertilization (hpf). Differentially expressed genes can be
      grouped into two categories, early genes that are expressed at 5hpf and genes
      expressed at 48/72/120hpf. Furthermore, we report the utilization of cDNA
      microarray technology to investigate the adaptive molecular responses of
      zebrafish to hypoxia during development. Our study provides the first utilization
      of cDNA microarray in the zebrafish and reveals dynamic changes in levels of gene
      expression in relation to development and survival of the zebrafish embryos under
      hypoxic stress.

PMID- 12207890
TI  - Differential gene expression in retinoic acid-induced differentiation of acute
      promyelocytic leukemia cells, NB4 and HL-60 cells.
AB  - Acute promyelocytic leukemia (APL) is characterized by a specific chromosome
      translocation t(15;17), which results in the fusion of the promyelocytic leukemia
      gene (PML) and retinoic acid receptor alpha gene (RARalpha). APL can be
      effectively treated with the cell differentiation inducer all-trans retinoic acid
      (ATRA). NB4 cells, an acute promyelocytic leukemia cell line, have the t(15;17)
      translocation and differentiate in response to ATRA, whereas HL-60 cells lack
      this chromosomal translocation, even after differentiation by ATRA. To identify
      changes in the gene expression patterns of promyelocytic leukemia cells during
      differentiation, we compared the gene expression profiles in NB4 and HL-60 cells
      with and without ATRA treatment using a cDNA microarray containing 10,000 human
      genes. NB4 and HL-60 cells were treated with ATRA (10(-6)M) and total RNA was
      extracted at various time points (3, 8, 12, 24, and 48h). Cell differentiation
      was evaluated for cell morphology changes and CD11b expression. PML/RARalpha
      degradation was studied by indirect immunofluoresence with polyclonal PML
      antibodies. Typical morphologic and immunophenotypic changes after ATRA treatment
      were observed both in NB4 and HL-60 cells. The cDNA microarray identified 119
      genes that were up-regulated and 17 genes that were down-regulated in NB4 cells,
      while 35 genes were up-regulated and 36 genes were down-regulated in HL60 cells.
      Interestingly, we did not find any common gene expression profiles regulated by
      ATRA in NB4 and HL-60 cells, even though the granulocytic differentiation induced
      by ATRA was observed in both cell lines. These findings suggest that the
      molecular mechanisms and genes involved in ATRA-induced differentiation of APL
      cells may be different and cell type specific. Further studies will be needed to
      define the important molecular pathways involved in granulocytic differentiation
      by ATRA in APL cells.

PMID- 12207892
TI  - Genetic and physical maps of jerker (Espn(je)) on mouse chromosome 4.
AB  - The jerker mutation causes degeneration of cochlea and vestibular sensory hair
      cells in mice. A frame-shift mutation in the actin bundling gene Espin (Espn)
      leads to hair bundle defects by disrupting the actin filament assembly in
      stereocilia. Previously, jerker was mapped to distal mouse chromosome 4. Here,
      analyzing 2536 informative meioses derived from two intersubspecific
      intercrosses, we localize jerker to a 0.51+/-0.14cM interval on chromosome 4. The
      following order and distances of genes and markers were determined: D4Mit180
      0.44+/-0.13cM-Hes2, Espn(je)-0.08+/-0.06cM-D4Mit356-0.28+/-0.1cM-D4Mit208. A
      300kb physical bacterial artificial chromosome (BAC) contig was generated
      containing the Espn(je) locus. The human homologous region maps to 1p36.31. We
      present a detailed high-resolution genetic and physical map of markers located at
      distal chromosome 4 and demonstrate concordance of Espn with jerker.

PMID- 12207894
TI  - GSH-dependent peroxidase activity of the rice (Oryza sativa) glutaredoxin, a
      thioltransferase.
AB  - Glutaredoxin (Grx) is a 12-kDa thioltransferase that reduces disulfide bonds of
      other proteins and maintains the redox potential of cells. In addition to its
      oxidoreductase activity, we report here that a rice Grx (OsGrx) can also function
      as a GSH-dependent peroxidase. Because of this antioxidant activity, OsGrx
      protects glutamine synthetase from oxidative damage. Individually replacing the
      conserved Cys residues in OsGrx with Ser shows that Cys(23), but not Cys(26), is
      essential for the thioltransferase and GSH-dependent peroxidase activities.
      Kinetic characterization of OsGrx reveals that the maximal catalytic efficiency
      (V(max)/K(m)) is obtained with cumene hydroperoxide rather than H(2)O(2) or t
      butyl hydroperoxide.

PMID- 12207893
TI  - The antioxidant cocktail effective microorganism X (EM-X) inhibits oxidant
      induced interleukin-8 release and the peroxidation of phospholipids in vitro.
AB  - The antioxidant beverage EM-X is derived from the ferment of unpolished rice,
      papaya, and sea-weeds with effective microorganisms. Oxidative stress enhances
      the expression of proinflammatory genes, causing the release of the chemokine
      interleukin-8 (IL-8), which mediates a multitude of inflammatory events. Human
      alveolar epithelial cells (A549) were treated with H(2)O(2) (100 microM) or TNF
      alpha (10ng/ml) alone or with the addition of EM-X (100 microl/ml), incubated for
      20h, and the release of IL-8, measured using ELISA. EM-X inhibited the release of
      IL-8 at the transcriptional level in A549 cells. EM-X also decreased the
      iron/ascorbate dependent peroxidation of ox-brain phospholipids in a
      concentration dependent manner. A TEAC value of 0.10+/-0.05mM was obtained for EM
      X, indicating antioxidant potential. We suggest that the anti-inflammatory and
      antioxidant properties of EM-X are dependent on the flavonoid contents of the
      beverage.

PMID- 12207895
TI  - Expression of hepatitis B virus X (HBx) gene is up-regulated by adriamycin at the
      post-transcriptional level.
AB  - Hepatitis B virus (HBV) X protein (HBx) is thought to be involved in the
      development of liver cancer and alteration of cellular HBx level may influence
      the pathological progression of HBV-induced liver diseases. We found that the
      cellular levels of HBx mRNA transcript and protein in cells were greatly enhanced
      by adriamycin, a topoisomerase II inhibitor. Up-regulation of HBx mRNA by
      adriamycin was also observed in HBx transgenic mice, which was accompanied with a
      significant increase of VEGF mRNA, the downstream target of HBx. When we
      investigated the underlying mechanism, we found that half-life of HBx mRNA in HBx
      expressing Chang cells was about 3h, but was prolonged to >6h in the presence of
      adriamycin. Moreover, half-life of rapidly degrading HBx protein was determined
      as about 15min however, it remained almost constant until 60min in the presence
      of adriamycin. These results provide the first evidence that the cellular level
      of HBx gene can be increased at the post-transcriptional level.

PMID- 12207896
TI  - Mammalian Apg12p, but not the Apg12p.Apg5p conjugate, facilitates LC3 processing.
AB  - A dynamic membrane rearrangement occurs in cells during autophagy to form
      autophagosomes. In this dynamic process, two ubiquitin-like modifications, Apg12p
      conjugation and LC3-modification, are essential for the formation of
      autophagosomes. Apg7p and Apg10p catalyze the conjugation of Apg12p to Apg5p. The
      same Apg7p and Apg3p catalyze the processing of LC3 to a membrane-bound form, LC3
      II. In this paper, we investigated whether Apg12p has an influence on the second
      LC3-modification system. A cross-linking experiment revealed that Apg3p interacts
      with the endogenous Apg12p.Apg5p conjugate. However, Apg3p itself interacts with
      free Apg12p more preferentially than the Apg12p.Apg5p conjugate, when free Apg12p
      exists. When Apg12p was overexpressed, LC3 processing was significantly enhanced
      in the presence of Apg7p. In contrast, when the Apg12p.Apg5p conjugate itself was
      accumulated by the overexpression of Apg12p and Apg5p, LC3 processing was
      dominantly inhibited, even in the presence of Apg7p. These results indicate that
      both Apg12p and the Apg12p.Apg5p conjugate are regulatory factors for LC3
      processing.

PMID- 12207897
TI  - Nitration of PECAM-1 ITIM tyrosines abrogates phosphorylation and SHP-2 binding.
AB  - Platelet-endothelial cell adhesion molecule-1 (PECAM-1) is a cell adhesion
      molecule with a cytoplasmic immunoreceptor tyrosine-based inhibitory motif (ITIM)
      that, when phosphorylated, binds Src homology 2 domain-containing protein
      tyrosine phosphatase (SHP-2). PECAM-1 is expressed at endothelial cell junctions
      where exposure to inflammatory intermediates may result in post-translational
      amino acid modifications that affect protein structure and function. Reactive
      nitrogen species (RNS), which are produced at sites of inflammation, nitrate
      tyrosine residues, and several proteins modified by tyrosine nitration have been
      found in diseased tissue. We show here that the RNS, peroxynitrite, induced
      nitration of both full-length cellular PECAM-1 and a purified recombinant PECAM-1
      cytoplasmic domain. Mass spectrometric analysis of tryptic fragments revealed
      quantitative nitration of ITIM tyrosine 686. A synthetic peptide containing 3
      nitrotyrosine at position 686 could not be phosphorylated nor bind SHP-2. These
      data suggest that ITIM tyrosine nitration may represent a mechanism for
      modulating phosphotyrosine-dependent signal transduction pathways.

PMID- 12207898
TI  - Uptake and intracellular fate of gelonin, a ribosome-inactivating protein, in rat
      liver.
AB  - Gelonin, a type 1 ribosome-inactivating protein, has been used as toxin conjugate
      for several therapeutic purposes. We have investigated the endocytosis of gelonin
      by rat liver in vivo. Subcellular distribution of [125I]gelonin was established
      after differential and isopycnic centrifugation. Fractions were analyzed for acid
      soluble and acid-precipitable radioactivity. Results show that gelonin is rapidly
      cleared from the blood and within 15min reaches a peak (25% of total injected) in
      the liver. With time, radioactivity associated with the liver markedly decreases.
      Two important observations are made: (a) Radioactivity associated with all
      fractions, at any time point, is greater than 80% acid precipitable. (b) Even at
      5min, a significant amount of intact gelonin is present in the cytosolic
      fraction. Our work suggests that, though gelonin is rapidly cleared from the
      blood, there are still intact molecules that have entered the cytosol where they
      could exert their toxic effect.

PMID- 12207899
TI  - Fertilization in Sepia officinalis: the first mollusk sperm-attracting peptide.
AB  - Egg mass extract was used to characterize regulatory peptides, involved in the
      successive steps of egg-laying of the cuttlefish Sepia officinalis. Among these
      peptides, a C-terminally amidated hexapeptide revealed a sperm-attracting
      activity. MALDI-TOF MS (matrix-assisted laser desorption ionization-time of
      flight mass spectrometry) and Edman degradation led to a peptide of m/z 596.6 and
      the following primary sequence: Pro-Ile-Asp-Pro-Gly-Val-CO(NH2). From
      concentrations as low as 10(-17)M, the PIDPGVamide was able to attract freshly
      dissected spermatozoa. Nano-ESI-Q-TOF MS (nano-electrospray ionization-quadrupole
      time-of-flight mass spectrometry) analysis established the quantitative
      occurrence of this peptide in different egg structures. The PIDPGVamide appears
      to be synthesized in oocytes during vitellogenesis and released by the embedded
      oocytes in the external media during egg-laying to facilitate fertilization by
      increasing chances of gamete collision. This novel peptide called SepSAP for
      Sepia sperm attracting peptide is the first sperm-attracting peptide, identified
      in mollusks or even in protostomians.

PMID- 12207900
TI  - A sugarcane cystatin: recombinant expression, purification, and antifungal
      activity.
AB  - Plants possess several defense mechanisms against pathogenic attack. One of these
      defenses is the use of protease inhibitor proteins, which interfere in the
      development and growth of pathogens. Sugarcane productivity can be impacted by
      the plant's susceptibility to fungal diseases that result in production losses. A
      relevant line of investigation, therefore, is into the plant's natural defense
      mechanisms for the control of phytopathogens using cystatins-proteins that
      specifically inhibit cysteine proteases. In this paper, we discuss the
      expression, in Escherichia coli, of a sugarcane cystatin, its purification,
      antifungal activity, and circular dichroism to monitor correct folding. These
      studies revealed a secondary structure similar to that of the oryzacystatin I of
      rice. Moreover, the purified protein proved capable of inhibiting the growth of
      the filamentous fungus Trichoderma reesei, suggesting that it can also be
      employed to inhibit the growth of pathogenic sugarcane fungi.

PMID- 12207901
TI  - Single nucleotide polymorphisms of estrogen receptor alpha in human renal cell
      carcinoma.
AB  - Estrogens and their receptors (ERs) have been shown to play a role in various
      cancers. We hypothesize that polymorphisms and genotypic changes of the ERalpha
      gene are involved in renal cell carcinoma. To test this hypothesis, DNA samples
      from 113 cases of human renal cell cancer were analyzed by sequence-specific
      polymerase chain reaction to determine the genotypic frequency of six different
      polymorphic loci on ERalpha gene (codon 10 T-->C, codon 87 G-->C, codon 243 C-
      >T, codon 325 C-->G, codon 594 G-->A, and intron 1 C-->T). The relative risk of
      variant genotype was calculated by comparison with 200 healthy controls. The
      results of this study demonstrate that the distribution of genotypes on codon 10
      differs between renal cancer patients and healthy normal controls (p<0.05). The
      relative risk of the genotype 10C/C was calculated as 2.51. No differences in
      genotypes were observed at all other loci. We also analyzed DNA from pairs of
      cancerous and normal tissues from 96 cases of human renal cell cancer to
      characterize genotypic changes at these loci. Genotypic changes were detected in
      nine cancer samples on exon 1 (codons 10 and 87) of ERalpha, although none were
      detected at other regions. The present study demonstrates for the first time that
      codon 10 polymorphism on exon 1 of ERalpha may be involved in renal cancer risk.

PMID- 12207902
TI  - Binding patterns of vanadium ions with different valence states to human serum
      transferrin studied by HPLC/high-resolution ICP-MS.
AB  - Vanadium (V) is an essential metal for mammals and has different valence states.
      In blood, V is bound to serum transferrin (Tf), a glycoprotein which has two
      metal-binding sites, and carbonate is generally required for the binding. In this
      study, the binding patterns of V(III), V(IV), and V(V) to human serum Tf (hTf)
      were analyzed using an HPLC system equipped with an anion-exchange column and
      directly connected to a high-resolution inductively coupled plasma-mass
      spectrometer for metal detection (51V). In affinity to hTf, the three ions were
      ranked V(III)>V(IV)>V(V) in the presence of bicarbonate and V(III) reverse
      congruent V(IV)>V(V) in the absence. Intermediates in the "open forms" binding to
      the respective sites were detected at the initial stage. V(IV) and V(V) were
      bound to the N-lobe site in the "closed form" and "open form," respectively. In
      the absence of bicarbonate, V ions with respective valence states were bound to
      hTf in the "open form." In terms of binding to hTf, tri-valent V was most
      favorable in the presence of bicarbonate.

PMID- 12207903
TI  - Molecular cloning of a novel immunoglobulin superfamily gene preferentially
      expressed by brain and testis.
AB  - We have cloned and characterized a novel gene from both human and mouse that
      encodes a new member of the immunoglobulin superfamily. The gene is
      preferentially expressed in both brain and testis, and hence, termed BT-IgSF
      (brain- and testis-specific immunoglobulin superfamily). The predicted protein
      consists of V-type and C2-type immunoglobulin domains as well as a hydrophobic
      signal sequence, a single transmembrane region, and a cytoplasmic domain. Human
      BT-IgSF protein (431 amino acids) is 88% identical to the mouse protein (428
      amino acids) and both show significant homology to coxsackie and adenovirus
      receptor (CAR) and endothelial cell-selective adhesion molecule (ESAM). We
      examined the expression of BT-IgSF with various cultured cells and found that the
      gene was expressed in both neurons and glial cells in vitro. Furthermore, the
      expression was preferentially detected in pyramidal cell layers of the dentate
      gyrus and hippocampus and in commissure fibers of the corpus callosum, in brain
      tissue sections examined. These findings suggest that BT-IgSF plays a role in the
      development or function of the central nervous system.

PMID- 12207904
TI  - A ubiquitin-interacting motif from Hrs binds to and occludes the ubiquitin
      surface necessary for polyubiquitination in monoubiquitinated proteins.
AB  - The ubiquitin-interacting motif (UIM) is a short, approximately 20 residue,
      structural element, which is present in, but not limited to, the proteins
      involved in endocytotic and proteasomal degradation. UIMs facilitate endocytotic
      vesicular sorting of the monoubiquitinated proteins and may be important for the
      targeting of the polyubiquitinated proteins to the proteasome. Using
      heteronuclear NMR backbone and side-chain chemical shift mapping of the ubiquitin
      interaction surface, the UIM from the hepatocyte growth factor-regulated tyrosine
      kinase substrate, Hrs, specifically binds to the ubiquitin hydrophobic surface
      using UIM's well-conserved central helical LALAL motif. Molecular modeling of the
      ubiquitin:UIM_Hrs complex suggests that binding occurs through a specific
      interaction of Leu263 and Leu267 of the UIM_Hrs with two ubiquitin hydrophobic
      patches located in close proximity to the ubiquitin major polyubiquitination
      site, Lys48. Intramolecular binding of ubiquitin to a UIM in monoubiquitinated
      proteins would render Lys48 unavailable for further ubiquitination, thus,
      explaining the absolute requirement of UIMs for monoubiquitination. Two leucines,
      Leu265 and Leu269, located on the opposite face of UIM_Hrs can also interact,
      albeit less favorably than Leu263 and Leu267, with the ubiquitin hydrophobic
      patches, suggesting a possible mode for polyubiquitin:UIM binding and apparent
      preference of UIMs for polyubiquitins.

PMID- 12207906
TI  - Hemolytic activity and developmental expression of pore-forming peptide,
      clonorin.
AB  - Peptides pore-forming in cell membrane have been identified from a wide range of
      animals. A putative pore-forming peptide deduced from a cDNA clone of Clonorchis
      sinensis (clonorin) was predicted to consist of four amphipathic alpha-helices.
      Clonorin contained six invariably conserved cysteine residues, identified to form
      three disulfide bonds. These predicted structural features are highly homologous
      with pore-forming peptides, the amoebapores. Recombinant clonorin showed
      hemolytic activity toward rabbit erythrocytes. The hemolytic activity of C.
      sinensis extract increased dose-dependently and was inhibited by anti-clonorin
      immune sera. The clonorin was expressed developmentally in juvenile and adult
      flukes and localized in the intestinal epithelium of adult flukes. It is proposed
      that, through lysing host cellular components, clonorin could enhance proteolytic
      digestion in the intestine of C. sinensis.

PMID- 12207905
TI  - Identification of HIV-1 nucleocapsid protein: nucleic acid antagonists with
      cellular anti-HIV activity.
AB  - The crucial functions of HIV-1 nucleocapsid-p7 protein (NC-p7) at different
      stages of HIV replication are dependent on its nucleic acid binding properties.
      In this study, a search has been made to identify antagonists of the interaction
      between NC-p7 and d(TG)(4). A chemical library of approximately 2000 small
      molecules (the NCI Diversity Set) was screened, of the 26 active inhibitors that
      were identified, five contained a xanthenyl ring structure. Further analysis of
      63 structurally related compounds led to the identification of 2,3,4,5
      tetrachloro-6-(4('),5('),6(')-trihydroxy-3(')-oxo-3H-xanthen-9(')-yl)benzoic
      acid, which binds to NC-p7 stoichiometrically. This compound exerted a
      significant anti-HIV activity in vitro with an IC(50) of 16.6+/-4.3 microM
      (means+/-SD). Synthetic variants lacking the two hydroxyls at positions 4(') and
      5(') in the xanthenyl ring system failed to bind NC-p7 and showed significantly
      less protection against HIV infection. Molecular modeling predicts that these
      hydroxyl groups would bind to the amide nitrogen of Gly(35) with other contacts
      at the carbonyl oxygens of Gly(40) and Lys(33).

PMID- 12207907
TI  - A beta-tubulin-like cDNA expressed specifically in elongating cotton fibers
      induces longitudinal growth of fission yeast.
AB  - Using cDNA Representational Difference Analysis (RDA) techniques, we isolated a
      cDNA that was expressed specifically in cotton fibers but not in the ovules of a
      fuzzless-lintless mutant (fl). We designated it as Gh-BTubL for it shares high
      sequence identity with known plant and yeast beta-tubulins. RT-PCR and robotic
      cDNA dot blot analyses indicated that the expression of Gh-BTubL was correlated
      with the elongation pattern of cotton fibers. In situ hybridization results
      verified that there was no Gh-BTubL mRNA in fl ovules while it was easily
      detected in the elongating wild type cotton fiber cells. Overexpression of Gh
      BTubL in fission yeast induced longitudinal growth of the host cells by 1.74
      fold, with no apparent effect on other aspects of the host cells. We suggest that
      Gh-BTubL plays an important role in cotton fiber elongation and we believe that
      elucidation of the control mechanisms for expression of tubulin-like proteins may
      help improve fiber quality and productivity.

PMID- 12207908
TI  - The conformational alteration of the mutated extracellular domain of Fas in an
      adult T cell leukemia cell line.
AB  - Fas (APO-1/CD95) is a cell surface receptor involved in apoptosis. Almost all
      adult T cell leukemia (ATL) cells express abundant Fas antigen and show apoptosis
      induced by IgM anti-Fas monoclonal antibody (mAb). We established the ATL cell
      line, RSO4, which was obtained from Fas-sensitive ATL cell line SO4 and showed
      resistance to apoptosis induced by the mAb. By sequencing analysis of Fas gene,
      we found the mutation with the transition of A-G at nucleotide 373 at exon 2
      among the extracellular domain (ECD), resulting in substitution of arginine for
      histidine. The molecular modeling suggested the definitive conformational
      alteration around residues 52-58 among the cysteine-rich domain (CRD) 1. It was
      suggested that the polymerization of Fas antigen, which was the essential process
      for the efficient induction of apoptosis, was interfered by the alteration of
      CRD1, and that this portion, named the "histidine-rich region," played a critical
      role in Fas assembly.

PMID- 12207909
TI  - Proteasome inhibitors regulate tyrosine phosphorylation of IRS-1 and insulin
      signaling in adipocytes.
AB  - Insulin rapidly stimulates the tyrosine kinase activity of its receptor,
      resulting in the phosphorylation of insulin receptor substrates (IRS), which in
      turn associates and activates PI 3-kinase, leading to an increase in glucose
      uptake. Phosphorylation of IRS proteins and activation of downstream kinases by
      insulin are transient and the mechanisms for the subsequent downregulation of
      their activity are largely unknown. We report here that the insulin-induced IRS-1
      tyrosine phosphorylation and PI 3-kinase association to IRS-1 were strongly
      sustained by the proteasome inhibitors, MG132 and lactacystin. In contrast, no
      effect was detected on the insulin receptor and IRS-2 tyrosine phosphorylation.
      Interestingly, lactacystin also preserved PKB activation and insulin-induced
      glucose uptake. In contrast, calpeptin, a calpain inhibitor, was ineffective.
      Tyrosine phosphatase assays were also performed, showing that lactacystin was not
      functioning directly as a tyrosine phosphatase inhibitor "in vitro." In
      conclusion, proteasome inhibitors can regulate the tyrosine phosphorylation of
      IRS-1 and the downstream insulin signaling pathway, leading to glucose transport.

PMID- 12207910
TI  - IL-6 activates HSP72 gene expression in human skeletal muscle.
AB  - To determine whether the cytokine interleukin (IL)-6 induces heat shock protein
      (HSP) 72 gene expression in skeletal muscle, 18 healthy, young men had either a
      high dose of IL-6 (HiIL-6; n=6), low dose IL-6 (LoIL-6; n=6), or saline (CON;
      n=6) infused into one femoral artery for 3h. Muscle biopsies were obtained from
      the vastus lateralis of the infusion limb and samples were analyzed for HSP72
      mRNA. In addition, blood samples were collected from the femoral vein of the
      infusion limb and analyzed for plasma IL-6. In CON, femoral vein IL-6
      concentration remained at basal levels throughout the experiment but in both HiIL
      6 and LoIL-6, femoral vein IL-6 concentrations were markedly elevated (P<0.05).
      HSP72 gene expression did not increase above resting levels in CON. In contrast,
      in both HiIL-6 and LoIL-6, HSP72 mRNA increased (P<0.05) 2.5- and 2.3-fold,
      respectively after 30min of infusion and remained elevated (P<0.05) for 24h
      following infusion. These data demonstrate that IL-6 can rapidly induce HSP72
      gene expression in human skeletal muscle.

PMID- 12207911
TI  - ADP-ribose stimulates the calcium release channel RyR1 in skeletal muscle of rat.
AB  - The Ca(2+) mobilizing metabolite cyclic ADP-ribose has been shown to release
      Ca(2+) from intracellular ryanodine sensitive stores in many cells. However, the
      activation of the ryanodine receptor of skeletal muscle by cADP-ribose (cADPr)
      and its precursor and metabolite (beta-NAD(+) and ADPr) remains to be discussed.
      We studied the effect of ADPr on the Ca(2+) release channel of skeletal muscle
      RyR1 after incorporation of microsomes isolated from fast muscles of rat in
      planar lipid bilayers. We observed an increase in the electrophysiological
      activity of the channel after addition of ADPr (10 microM) at micromolar Ca(2+)
      concentrations, characterized by a time-lag. The increase in P(o) is mainly due
      to an increase in the open frequency. The long time course observed for the
      development of the ADPr effect may indicate that this activation induces a change
      in the conformation of the RyR1 channel, which increases its sensitivity to
      calcium.

PMID- 12207912
TI  - Cytochrome bo(3) from Escherichia coli: the binding and turnover of nitric oxide.
AB  - The reaction of nitric oxide (NO) with fast and reduced cytochrome bo(3)(cyt
      bo(3)) from Escherichia coli has been investigated. The stoichiometry of NO
      binding to cyt bo(3) was determined using an NO electrode in the [NO] range 1-14
      microM. Under reducing conditions, the initial decrease in [NO] following the
      addition of cyt bo(3) corresponded to binding of 1 NO molecule per cyt bo(3)
      functional unit. After this "rapid" NO binding phase, there was a slow, but
      significant rate of NO consumption ( approximately 0.3molNOmol bo(3)(-1)min(-1)),
      indicating that cyt bo(3) possesses a low level of NO reductase activity. The
      binding of NO to fast pulsed enzyme was also investigated. The results show that
      in the [NO] range used (1-14 microM) both fast and pulsed oxidised cyt bo(3) bind
      NO with a stoichiometry of 1:1 with an observed dissociation constant of
      K(d)=5.6+/-0.6 microM and that NO binding was inhibited by the presence of Cl(-).
      The binding of nitrite to the binuclear centre causes spectral changes similar to
      those observed upon NO binding to fast cyt bo(3). These results are discussed in
      relation to the model proposed by Wilson and co-workers [FEBS Lett. 414 (1997)
      281] where the binding of NO to Cu(B)(II) results in the formation of the
      nitrosonium (Cu(B)(I)-NO(+)) complex. NO(+) then reacts with OH(-), a Cu(B)
      ligand, to form nitrite, which can bind at the binuclear centre. This work
      suggests for the first time that the binding of NO to oxidised cyt bo(3) does
      result in the reduction of Cu(B).

PMID- 12207913
TI  - TEF-1 transcription factors regulate activity of the mouse mammary tumor virus
      LTR.
AB  - The mouse mammary tumor virus long terminal repeat (LTR) is a potent
      transcriptional enhancer. We identified several putative binding sites for the
      TEF-1 family of transcription factors (TEF-1, RTEF-1, DTEF-1, and ETF) in the
      proximal negative regulatory element of the LTR. Gel mobility shift assays
      revealed strong TEF-1 factor binding to one site using nuclear extracts from CV-1
      cells and from the human breast cancer cell line MCF-7. Mutation of this site
      increased basal activity of the LTR. In transient transfection assays, TEF-1
      squelched the basal LTR activity and completely abrogated the response to the
      glucocorticoid dexamethasone. RTEF-1 and DTEF-1 had little effect on the basal
      activity, whereas ETF activated the LTR. These TEF-1 factors also interfered with
      the response to dexamethasone. Taken together, our results reveal an important
      new role for TEF-1 factors in regulating MMTV LTR activity and suggest that TEF-1
      factors might participate in mammary tumorigenesis.

PMID- 12207914
TI  - Quantitative analysis for human glucocorticoid receptor alpha/beta mRNA in IBD.
AB  - We have previously reported that in peripheral blood mononuclear cells (PBMC),
      the augmented expression of the beta isoform of the human glucocorticoid receptor
      (hGRbeta), as a putative dominant negative regulator of glucocorticoid action, is
      associated with glucocorticoid (GC) unresponsiveness of UC patients. In this
      study, we quantified the levels and serial changes of hGR transcripts in PBMC of
      IBD patients by a real-time fluorescence monitoring of PCR. As results, relative
      hGRbeta mRNA expression was significantly higher in the active stage of UC than
      in inactive periods of UC or CD patients. Longitudinal analysis revealed that
      hGRbeta mRNA expression in UC was increased after the relapse of inflammation,
      suggesting that the overproduction of cytokines during inflammation may be
      responsible. In in vitro culture experiments of human lymphoid cell (CEM) and
      human PBMC, IL-7, and IL-18 increased hGRbeta mRNA expression in these cells but
      GC itself did not. Through these analyses, it is indicated that the inflammatory
      cytokines altered the splicing condition of the primary transcript of hGR gene in
      IBD patients.

PMID- 12207916
TI  - Improvement of human interferon HUIFNalpha2 and HCV core protein expression
      levels in Escherichia coli but not of HUIFNalpha8 by using the tRNA(AGA/AGG).
AB  - High-level expression from one particular heterologous gene in Escherichia coli
      generally requires the optimization of codon usage. Genes encoding for Hepatitis
      C virus core protein (HCcAg), human interferon alpha2 and 8 subtypes (HUIFNalpha2
      and HUIFNalpha8) show a high content of AGA/AGG codons. These are encoded by the
      product of the dnaY gene in E. coli. The proteins used in this work have a high
      therapeutic value and were used as models for studying the effects of these rare
      codons on the efficiency of heterologous gene expression in E. coli. Expression
      plasmids were constructed to express any of these proteins and the dnaY gene
      product simultaneously in E. coli. After dnaY gene expression, HCcAg, and
      HUIFNalpha2 expression levels increased 5 and 3 times, respectively. However,
      HUIFNalpha8 expression was barely detected either supplying or not the additional
      dnaY gene product. These results suggest that the high frequency of AGA/AGG
      codons present in the HCcAg and HUIFNalpha2 genes could be one of the factors
      limiting its expression in E. coli. Nevertheless, for HUIFNalpha8 it seems that
      other factors prevail upon the lack of dnaY product. Data presented here for
      HCcAg and HUIFNalpha2 expressions proved the value of this approach to obtain
      therapeutic proteins in E. coli.

PMID- 12207915
TI  - Inhibition of NF-kappaB activation by merlin.
AB  - The neurofibromatosis type 2 (NF2) gene encodes an ezrin-radixin-moesin (ERM)
      related protein, referred to as either merlin or schwannomin, that is known to be
      a tumor suppressor. NF-kappaB signaling is known to be important for controlling
      cellular proliferation and protecting against apoptosis. In this report, merlin
      was demonstrated to be effective in suppressing the NF-kappaB signaling pathway
      in NIH3T3 and C6 cells. In addition, merlin blocked the tumor necrosis factor
      alpha (TNF-alpha)-induced NF-kappaB-DNA binding mediated via the inhibition of
      degradation of IkappaBalpha and blocked the activation of NF-kappaB-dependent
      transcription. A reporter gene assay using deletion mutants of NF2 showed that
      the N-terminus (amino acids 1-130) of merlin may be important for its inhibition
      of NF-kappaB activation. These results show that merlin acts as a negative
      regulator of the NF-kappaB signaling pathway.

PMID- 12207917
TI  - Inhibition of yeast ribosomal stalk phosphorylation by Cu-Zn superoxide
      dismutase.
AB  - Reversible phosphorylation of acidic ribosomal proteins of Saccharomyces
      cerevisiae is an important mechanism, regulating the number of active ribosomes.
      The key role in regulation of this process is played by specific, second
      messenger-independent protein kinases. A new protein-inhibitor regulating
      activity of PK60S kinase has been purified from yeast extracts and characterised.
      Peptide mass fingerprinting (PMF) and amino-acid sequence analysis by Post Source
      Decay (PSD) have identified the inhibitor as a Cu-Zn superoxide dismutase (SOD).
      Inhibition by SOD is competitive with respect to protein substrates-P proteins
      and 80S ribosome-with K(i) values of 3.7 microM for P2A protein and 0.6 microM
      for 80S ribosomes. A close correlation was found between the state of
      phosphorylation of P proteins in diauxic shift and logarithmic growth yeast cells
      and activity of SOD. The possible mechanism of regulation of PK60S activity, and
      participation of SOD protein in regulation of 80S-ribosome activity in stress
      conditions, is discussed.

PMID- 12207918
TI  - Abeta(25-35) and Abeta(1-40) act on different calcium channels in CA1 hippocampal
      neurons.
AB  - The acute effects of beta-amyloid (25-35) and (1-40) on high voltage activated
      calcium channels were compared in CA1 pyramidal cells of adult mouse hippocampal
      slices using the whole-cell patch-clamp recording. Bath application of oligomeric
      beta-amyloid (25-35) reversibly increased the barium current (I(Ba)) to 1.61
      (normalized amplitude), while oligomeric beta-amyloid (1-40) reversibly enhanced
      the I(Ba) to 1.74. Reverse-sequence beta-amyloid [(35-25) and (40-1)] had no
      effect. The effect of beta-amyloid (25-35) was blocked by nifedipine, a selective
      antagonist of L-type calcium channels. In contrast, the effect of beta-amyloid (1
      40) was not blocked by nifedipine and I(Ba) was enhanced to 4.96. It is concluded
      that these oligomeric peptides may act through different types of calcium
      channels and/or receptors. The toxicity of Abeta(25-35) implicates a potentiation
      of L-type calcium channels while the one of Abeta(1-40) is related to an increase
      of non-L-type calcium channels, which may involve an increase in transmitter
      release.

PMID- 12207919
TI  - Expression of a p67(phox) homolog in Caco-2 cells giving O(2)(-)-reconstituting
      ability to cytochrome b(558) together with recombinant p47(phox).
AB  - Human normal and transformed (Caco-2) colon tissues as well as guinea pig gastric
      mucosal cells express Nox1, which is a homolog of the phagocyte NADPH oxidase
      subunit, gp91(phox) of membrane-bound cytochrome b(558). It was reported that
      Nox1-transfection to NIH 3T3 cells could provide O(2)(-)-generating ability,
      independently of regulatory cytosolic factors (Rac2, p67(phox), and p47(phox))
      that are obligatory in the phagocyte oxidase system. Here, we detected and
      sequenced a p67(phox) homolog in Caco-2 almost identical to the neutrophil
      sequence, except for three nucleotide substitutions, two of which changed lysines
      181 and 328 to arginines. Investigation of its ability to support O(2)(-)
      generation in cell-free reconstitution experiments combining with neutrophil
      cytochrome b(558) showed O(2)(-)-generation, provided that recombinant p47(phox)
      was added. This result demonstrates that the intrinsic p67(phox) homolog of Caco
      2 was able to function as a phagocyte p67(phox) for cytochrome b(558). The
      requirement of p47(phox) addition suggested that this component was absent in
      Caco-2 cells. Caco-2 membranes, used as a source of Nox1 in place of cytochrome
      b(558), did not show significant O(2)(-)-generation, which was mainly explained
      by their very little Nox1 expression.

PMID- 12207920
TI  - A novel, anchorless streptococcal surface protein that binds to human
      immunoglobulins.
AB  - We have characterized a novel surface protein from urea extract of whole cells of
      group A Streptococcus pyogenes (GAS). A major protein band (35kD) was found to
      hybridize with human IgG by Western blotting. A search of the N-terminal amino
      acid sequence of this protein by using the GAS genome sequence database revealed
      an open reading frame that encoded a 38-kDa protein with a signal peptide
      sequence. We have named this protein streptococcal immunoglobulin-binding protein
      35 (Sib35). It was found to be an anchorless protein with no LPXTG motif,
      distinct from the M protein superfamily exhibiting immunoglobulin-binding
      activity, and partially secreted in the culture supernatant. Recombinant Sib35
      was also shown to bind human IgA and IgM. The sib35 gene was found in all GAS
      strains examined, but not in oral, group B, C, or G streptococcal strains. These
      results suggest that Sib35 is a unique immunoglobulin-binding protein in GAS.

PMID- 12207921
TI  - Mayaro virus infection cycle relies on casein kinase 2 activity.
AB  - Replication of Mayaro virus in Vero cells induces dramatic cytopathic effects and
      cell death. In this study, we have evaluated the role of casein kinase 2 (CK2)
      during Mayaro virus infection cycle. We found that CK2 was activated during the
      initial stages of infection ( approximately 36% after 4h). This activation was
      further confirmed when the enzyme was partially purified from the cellular lysate
      either by Mono Q 5/5Hr column or heparin-agarose column. Using this later column,
      we found that the elution profile of CK2 activity from infected cells was
      different from that obtained for control cell enzyme, suggesting a structural
      modification of CK2 after infection. Treatment of infected cells with a cell
      permeable inhibitor of CK2, dichloro-1-(beta-D-ribofuranosyl)benzimidazole (DRB),
      abolished the cytopathic effect in a dose-dependent manner. Together this set of
      data demonstrates for the first time that CK2 activity in host cells is required
      in Mayaro virus infection cycle.

PMID- 12207922
TI  - p130/p107 expression distinguishes adipogenic potential in primary myoblasts
      based on age.
AB  - Recent investigations have provided significant evidence that many mesodermally
      derived tissues contain stem cell-like precursors capable of being stimulated to
      undergo differentiation into a variety of cellular lineages. We have recently
      reported that primary myoblasts isolated from 23-month-old mice have an increased
      adipogenic potential when compared to their 8-month-old counterparts. To further
      characterize the degree of adipocyte differentiation in these myoblasts, we
      examined early and late markers of adipocyte differentiation. Within the first
      24h of adipocyte differentiation, expression of p130 and p107, two members of the
      retinoblastoma tumor suppressor gene family, are regulated and this event is an
      important one early in adipogenesis. Consistent with the increased adipogenic
      potential of the older myoblasts and in contrast to the younger cells, the
      p130:p107 pattern of expression is very similar to that observed in adipogenesis
      where there is a transient increase in p107 expression accompanied by a decrease
      in p130 expression. Interestingly, while these older cells accumulated lipid and
      expressed genes associated with lipid metabolism, they failed to express adipsin
      and leptin, two well-established markers of terminal adipocyte differentiation.
      These results suggest that older myoblasts are capable of initiating and
      progressing through the adipogenic program to a point where they express genes
      associated with lipid metabolism, but do not reach a terminally differentiated
      state. This finding may have important metabolic implications in the aging
      population.

PMID- 12207923
TI  - Homology modeling of the cellulose-binding domain of a pollen allergen from rye
      grass: structural basis for the cellulose recognition and associated allergenic
      properties.
AB  - A three-dimensional model of the cellulose-binding domain of the rye-grass pollen
      allergen Lol pI built by homology modeling is proposed as a structural scaffold
      for expansins and other expansin-related proteins. A groove and an extended strip
      of aromatic and polar residues presumably account for the cellulose-binding
      properties of the protein domain. Two of the four predicted T-cell epitopes
      readily exposed on the surface of the cellulose-binding domain match with
      previously reported IgE-binding regions. A close structural relationship occurs
      between the cellulose-binding and allergenic properties.

PMID- 12207924
TI  - Preparation and analysis of small unilamellar phospholipid vesicles of a uniform
      size.
AB  - The interaction of carbonmonoxyhemoglobin and heme with small unilamellar
      phospholipid vesicles was studied using dynamic light scattering. Addition of
      carbonmonoxyhemoglobin to
      dimyristoylphosphatidylcholine:dimyristoylphosphatidylserine small unilamellar
      vesicles resulted in an increase of average vesicle size from 17.4 to 32.0nm.
      Addition of heme to vesicles produced a smaller size increase, from 17.4 to
      21.0nm. Also reported is a method for preparing small unilamellar lipid vesicles
      of a uniform size, suitable for use in NMR spectroscopy.

PMID- 12207925
TI  - Smad pathway is activated in the diabetic mouse kidney and Smad3 mediates TGF
      beta-induced fibronectin in mesangial cells.
AB  - Activation of the transforming growth factor-beta (TGF-beta) system has been
      implicated in the pathological changes of diabetic nephropathy such as renal
      hypertrophy and accumulation of extracellular matrix. Streptozotocin-induced
      diabetic mice were used to examine whether the Smad pathway, which transduces the
      TGF-beta signal, is activated in the diabetic kidney, employing Southwestern
      histochemistry with labeled Smad-binding element (SBE) oligonucleotides and
      immunoblotting of nuclear protein extracts for Smad3. Mouse mesangial cells were
      used to study the role of Smads in mediating the effects of high glucose and TGF
      beta on fibronectin expression, using transient transfections of Smad expression
      vectors and TGF-beta-responsive reporter assays. By Southwestern histochemistry,
      the binding of nuclear proteins to labeled SBE increased in both glomeruli and
      tubules at 1, 3, and 6 weeks of diabetes. Likewise, immunoblotting demonstrated
      that nuclear accumulation of Smad3 was increased in the kidney of diabetic mice.
      Both increases were prevented by insulin treatment. In mesangial cells, high
      glucose potentiated the effect of low-dose TGF-beta1 (0.2ng/ml) on the following
      TGF-beta-responsive constructs: 3TP-Lux (containing AP-1 sites and PAI-1
      promoter), SBE4-Luc (containing four tandem repeats of SBE sequence), and the
      fibronectin promoter. Additionally, Smad3 overexpression increased fibronectin
      promoter activity, an effect that was enhanced by high ambient glucose or
      treatment with TGF-beta1 (2ng/ml). The TGF-beta-stimulated activity of the
      fibronectin promoter was prevented by transfection with either a dominant
      negative Smad3 or the inhibitory Smad7. We conclude that hyperglycemia activates
      the intrarenal TGF-beta/Smad signaling pathway, which then promotes mesangial
      matrix gene expression in diabetic nephropathy.

PMID- 12207926
TI  - Acidophilic character of yeast PID261/BUD32, a putative ancestor of eukaryotic
      protein kinases.
AB  - Yeast piD261/Bud32 and its homologues are present in eukaryotes and in archaea
      but not in bacteria and are believed to make up a primordial branch of the
      eukaryotic protein kinase superfamily. Here, we show that, at variance with the
      majority of Ser/Thr protein kinases which recognize phosphoacceptor sites
      specified by basic and/or proline residues, piD261 phosphorylates in vitro a
      number of acidic proteins and peptides, and it recognizes seryl residues
      specified by carboxylic side chains. These data suggest that recognition of
      acidic sites might have been a primordial trait of protein kinases, which was
      modified during evolution to cope with the increasing complexity of protein
      phosphorylation in eukaryotes.

PMID- 12207927
TI  - Successful inactivation of endogenous Oct-3/4 and c-mos genes in mouse
      preimplantation embryos and oocytes using short interfering RNAs.
AB  - Understanding oocyte maturation and early development in mammals is very
      important, especially because these cells serve as a source of materials useful
      in medical applications, such as ES cells. However, the limited availability of
      oocytes and embryos hampers the molecular dissection of the very early stage of
      mammalian development. Recently, the RNA interference technology has been
      acknowledged to be very effective and useful in diverse groups of cells,
      including mammalian cells. In this study, we examined whether short interfering
      RNAs (siRNAs) are applicable to mouse oocytes and preimplantation embryos, by
      targeting two genes, namely, Oct-3/4 and c-mos. siRNA injections successfully
      extinguished the production of these target genes. Moreover, the siRNA-injected
      oocytes and embryos showed phenotypes very similar to those exhibited by Oct-3/4-
      or Mos-knockout mice in previous studies. Accordingly, we concluded that siRNA is
      a useful tool in molecular studies on the early development of mouse.

PMID- 12207928
TI  - Apoptosis and muscle fibre loss in neuromuscular disorders.
AB  - The past decade has witnessed increasing evidence that besides necrosis,
      apoptotic cell death mechanisms contribute to muscle fibre loss in various
      neuromuscular conditions, including the muscular dystrophies, metabolic
      myopathies, and cases of denervation. The up-regulation of bax and bcl-2, both
      members of the bcl-2 family, indicate that the predominant effectors involve
      permeability transition pores in the mitochondrial membrane and subsequent
      caspase activation which confers the typical morphological and biochemical
      features of apoptosis such as DNA-fragmentation. It is likely that apoptotic
      degradation of nuclei and contractile elements is a localized event in muscle
      fibre segments leading to muscle fibre atrophy and finally loss in these
      disorders. Essential triggers of apoptosis seem to be homeostatic dysregulation
      as well as oxidative stress, with increased generation of free oxygen radicals
      and nitric oxide. In the absence of effective primary treatments, there is hope
      that interventions in muscle fibre apoptosis will bear promising therapeutic
      strategies.

PMID- 12207929
TI  - Congenital muscular dystrophy with adducted thumbs, ptosis, external
      ophthalmoplegia, mental retardation and cerebellar hypoplasia: a novel form of
      CMD.
AB  - At least six different forms of congenital muscular dystrophy are associated with
      structural changes of the central nervous system, and three of these have been
      mapped: merosin-deficient congenital muscular dystrophy on chromosome 6q2,
      Fukuyama congenital muscular dystrophy on chromosome 9q31, and muscle eye brain
      disease on chromosome 1p32. Walker-Warburg syndrome, congenital muscular
      dystrophy with calf hypertrophy, pontocerebellar hypoplasia, and normal eyes, and
      congenital muscular dystrophy with severe mental retardation and cerebellar cysts
      are nosologically distinct and have been excluded from the known congenital
      muscular dystrophy loci with structural changes of the central nervous system.
      Here, we describe a novel congenital muscular dystrophy syndrome which is
      phenotypically distinct from the recognized forms of congenital muscular
      dystrophy with brain involvement. Two siblings, a boy and a girl, were born to
      consanguineous parents from Sicily. Both children were born with adducted thumbs
      and toe contractures. They were floppy from birth, walked late, showed profound
      generalized muscle weakness including facial muscles, elevated creatine kinase
      levels of 200-700U/l, and histological changes compatible with muscular
      dystrophy. In addition, both showed ptosis, external ophthalmoplegia, mild mental
      retardation, and mild cerebellar hypoplasia on MRI. Immunocytochemistry showed
      normal expression of muscle membrane proteins including laminin alpha 2, laminin
      beta 2, and alpha-dystroglycan. Linkage analysis excluded the candidate loci on
      chromosomes 6q2, 9q31, and 1q32. The gene locus for congenital muscular dystrophy
      1B, MDC 1B, on chromosome 1q42 was also excluded. Adducted thumbs are a distinct
      clinical sign that has not been reported in congenital muscular dystrophy before
      and should facilitate recognition of further patients with this disorder.

PMID- 12207930
TI  - Clinical and imaging findings in six cases of congenital muscular dystrophy with
      rigid spine syndrome linked to chromosome 1p (RSMD1).
AB  - We report clinical and imaging findings in six cases from five families affected
      by the form of congenital muscular dystrophy with rigid spine linked to the locus
      rigid spine muscular dystrophy 1 on chromosome 1p35-36. All cases showed rigidity
      of the spine, predominant neck and trunk weakness and frequent and severe
      thoracic scoliosis. Respiratory impairment was always observed in the first
      decade. Muscle imaging showed a marked involvement of adductors, sartorius and
      biceps femoris while rectus femoris and gracilis were relatively spared. This
      pattern of selective muscle involvement was consistent in all six cases and could
      be easily observed on either computerised tomography or magnetic resonance
      imaging. The results of this study suggest that muscle imaging, in combination
      with clinical assessment can help to identify the rigid spine muscular dystrophy
      1 form of congenital muscular dystrophy and can help to target the appropriate
      genetic investigations.

PMID- 12207931
TI  - Quantitative assessment of calf circumference in Duchenne muscular dystrophy
      patients.
AB  - Duchenne muscular dystrophy is clinically characterised by progressive muscle
      weakness and a gradual increase in the size of some affected muscles, especially
      calf muscles. The extent of calf enlargement is usually determined by subjective
      visual assessment. The purpose of this study was to determine the extent of calf
      muscle enlargement in Duchenne muscular dystrophy (DMD) patients compared with
      healthy age matched boys by quantifying calf circumference. Calf circumference in
      the group of DMD patients is significantly increased. However, in individual
      patients calf enlargement can be feigned by a discrepancy between calf
      circumference and circumference of the upper leg and arm muscles as part of a
      general muscle atrophy.

PMID- 12207932
TI  - Charcot-Marie-Tooth neuropathy: clinical phenotypes of four novel mutations in
      the MPZ and Cx 32 genes.
AB  - Charcot-Marie-Tooth Hereditary Neuropathy is a heterogeneous syndrome associated
      with mutations in several different genes including peripheral myelin protein 22,
      myelin P0, connexin 32, and early growth response 2. There is considerable
      variability in the phenotypic expression of this syndrome and the relationship of
      this variability to mutation genotypes requires extensive analysis. Here we
      describe the phenotypes and genotypes of four new mutations underlying the
      Charcot-Marie-Tooth syndrome and document segregation with disease. Four families
      with Charcot-Marie-Tooth were ascertained, examined, and evaluated
      electrophysiologically. Each family had peripheral blood DNA screened for
      mutations in myelin protein 22, myelin P0, and connexin 32. Two families were
      found with new mutations in the myelin P0 gene: S140T in the extracellular domain
      and K236del in the cytoplasmic domain. All families showed segregation of the
      mutations with the Charcot-Marie-Tooth phenotype as did a new family with the
      rare G163R mutation in the membrane domain. A 49-year-old man with the S140T
      mutation demonstrated conduction block on electrophysiological testing. A family
      with a novel S49P mutation in the connexin 32 gene had a neuropathy with very
      slow nerve conduction. These new mutations in the myelin P0 and connexin 32 genes
      help to clarify the pathophysiology of the clinical Charcot-Marie-Tooth syndrome.
      The S140T mutation in myelin P0 can be associated with conduction block and
      Charcot-Marie-Tooth should be part of the differential diagnosis of that
      phenomenon. Mutations in the cytoplasmic domain of myelin P0 can cause clinical
      neuropathy. The S49P mutation in the connexin 32 gene can produce aspects of a
      demyelinating type of X-linked hereditary neuropathy.

PMID- 12207933
TI  - Hereditary neuropathy with liability to pressure palsies with a small deletion
      interrupting the PMP22 gene.
AB  - Hereditary neuropathy with liability to pressure palsies is associated with a
      deficiency in the Peripheral Myelin Protein 22 (PMP22). Most hereditary
      neuropathy with liability to pressure palsies cases are caused by a deletion of a
      1.5 Mb region on chromosome 17p11.2-12 encompassing the PMP22 gene. We describe a
      hereditary neuropathy with liability to pressure palsies family that lacks the
      common deletion, but carries a small deletion spanning the 3' region of the PMP22
      gene, causing only a partial deletion of one copy of the gene.

PMID- 12207934
TI  - Exclusion of serine palmitoyltransferase long chain base subunit 2 (SPTLC2) as a
      common cause for hereditary sensory neuropathy.
AB  - Recently point mutations in the SPTLC1 subunit of serine palmitoyltransferase
      have been shown to cause the common form of dominant hereditary sensory
      neuropathy (HSN1). Serine palmitoyltransferase (SPT) is a heterodimeric molecule
      made up of two subunits, SPTLC1 and SPTLC2. Twelve index patients from families
      with presumed genetic sensory neuropathies were screened for SPTLC2 mutations.
      These families comprised six multigenerational families, including two previously
      reported families not linked to the SPTLC1 locus on chromosome 9 and one
      multigenerational family with a complicated hereditary sensory neuropathy
      syndrome with associated palmar plantar keratosis, ataxia and spastic paraplegia.
      The remaining families included one consanguineous family with presumed recessive
      HSN with two affected siblings, one case of congenital sensory neuropathy and
      four sporadic cases with adult onset sensory neuropathy. No mutations in the
      SPTLC2 gene were found in any family. These results suggest that SPTLC2 mutations
      are not a common cause for genetic sensory neuropathies.

PMID- 12207935
TI  - A novel mitochondrial DNA tRNA(Ile) (A4267G) mutation in a sporadic patient with
      mitochondrial myopathy.
AB  - We describe a novel mutation in the mitochondrial tRNA(Ile) gene, an A to G
      transition at nucleotide position 4267, in a 37-year-old woman with myopathy,
      ataxia and sensorineural hearing loss. The A4267G mutation was heteroplasmic in
      several of the proband's tissues and single fibre analysis revealed significantly
      higher levels of mutated mitochondrial DNA in cytochrome c oxidase-deficient
      fibres than cytochrome c oxidase-positive fibres. It is predicted to disrupt a
      highly conserved base pair within the aminoacyl acceptor stem of the tRNA causing
      functional impairment, and as such fulfils all the accepted criteria for
      pathogenicity. Moreover, we were unable to detect the A4267G mutation in
      lymphocytes, buccal epithelia and hair of the patient's mother and two siblings,
      implying that the A4267G transition represents a sporadic, germline mutation.

PMID- 12207936
TI  - Na(+)/Ca(2+) exchange in human myotubes: intracellular calcium rises in response
      to external sodium depletion are enhanced in DMD.
AB  - This study aims to investigate the sodium/calcium exchanger expression in human
      co-cultured skeletal muscle cells and to compare the effects of Na(+)/Ca(2+)
      exchange activity in normal and dystrophic (Duchenne's muscular dystrophy) human
      co-cultured myotubes. For this purpose, variations of intracellular calcium
      concentration ([Ca(2+)](int)) were monitored, as the variations of the
      fluorescence ratio of indo-1 probe, in response to external sodium depletion.
      External sodium withdrawal induced [Ca(2+)](int) rises within several seconds in
      both normal and Duchenne's muscular dystrophy myotubes. These Na(+)-free-induced
      [Ca(2+)](int) elevations were attributed to the reverse mode of the Na(+)/Ca(2+)
      exchange mechanism since the phenomenon was dependent on extracellular calcium
      concentration ([Ca(2+)](ext)), and since it was sensitive to external Ni(2+)
      ions. Amplitudes of Na(+)-free-induced [Ca(2+)](int) rises were significantly
      greater in Duchenne's muscular dystrophy cells than in normal ones. Such a
      difference disappeared when the sarcoplasmic reticulum was pharmacologically
      blocked, suggesting that the reverse mode of the Na(+)/Ca(2+) exchange mechanism
      was able to generate enhanced calcium-induced calcium-release in Duchenne's
      muscular dystrophy myotubes. Immunostaining images of Na(+)/Ca(2+) exchanger
      (NCX) isoforms, obtained by confocal microscopy, revealed the presence of NCX1
      and NCX3 at the sarcolemmal level of both normal and Duchenne's muscular
      dystrophy myotubes. No differences were observed in the location of NCX isoforms
      expression between normal and Duchenne's muscular dystrophy co-cultured myotubes.

PMID- 12207937
TI  - Mutations in the nebulin gene can cause severe congenital nemaline myopathy.
AB  - Previously, we reported results indicating that nebulin was the gene causing the
      typical form of autosomal recessive nemaline (rod) myopathy. Here we describe the
      identification of mutations in the nebulin gene in seven offspring of five
      families affected by the severe congenital form of nemaline myopathy. One
      pregnancy was terminated on the grounds of foetal abnormality, while six affected
      infants died at ages ranging from the first day of life to 19 months. Only three
      of the six neonates were able to establish spontaneous respiration. Three had
      arthrogryposis. In three of the five families, the mutations were located in exon
      184. These mutations are predicted to cause absence of the C-terminal part of
      nebulin.

PMID- 12207939
TI  - Desmin - Protein Surplus Myopathies, 96th European Neuromuscular Centre (ENMC)
      sponsored International Workshop held 14-16 September 2001, Naarden, The
      Netherlands.

PMID- 12207938
TI  - Nebulin mutations in autosomal recessive nemaline myopathy: an update.
AB  - We report mutational analysis of the last 42 exons of the nebulin gene (NEB) in
      77 patients with various forms of nemaline myopathy. In addition to the
      previously described six mutations in five families, we identified 12 novel
      recessive mutations in 13 families. Affected individuals were homozygous for the
      mutations in five families and compound heterozygous in two, while in the
      remaining cases only one heterozygous mutation was identified. The majority of
      the mutations were frameshifts due to small deletions or insertions; also common
      were point mutations causing premature stop codons or abnormal splicing, while
      missense mutations appeared rare. There were no obvious mutational hotspots,
      although four unrelated patients showed mutations in the differentially expressed
      exon 177d, and another three showed mutations in exon 184. Most of the mutations
      are predicted to result in truncated or internally deleted proteins. Mutations in
      the differentially expressed exons are expected to reduce the nebulin isoform
      diversity necessary for normal muscle development.

PMID- 12207940
TI  - Cognitive function in children with spinal muscular atrophy.

PMID- 12207942
TI  - Amyotrophic lateral sclerosis with very slow progression.

PMID- 12207944
TI  - Proteoglycans in retina.
AB  - In this article, we summarize the roles of proteoglycans in retinal tissue.
      Chondroitin sulfate and heparan sulfate proteoglycans are the major constituents
      in proteoglycans expressed in retinal tissue. Soluble heparan sulfate
      proteoglycans are found in the extracellular matrices of the basement membrane,
      such as the inner limiting membrane and Bruch's membrane, whereas heparan sulfate
      proteoglycans with their membrane-binding domain are localized primarily in the
      neurites of retinal neuronal cells, indicating their role as receptors for
      cytokines. The distribution of chondroitin sulfate proteoglycans is classified
      into two regions: nerve fiber-rich layers such as the optic nerve, inner
      plexiform layer and outer plexiform layer, and the interphotoreceptor matrix
      (IPM). The expression in the nerve fiber-rich layers of several chondroitin
      sulfate proteoglycans, such as neurocan and phosphacan, is restricted in the
      nervous tissues, and is upregulated as retinal development proceeds, then
      decreases after maturation of the retina. In vitro data suggest that these
      proteoglycans regulate axon guidance and synapse formation during the development
      of nervous tissue. In contrast, in adult vertebrate retina, the IPM is a rich
      source of chondroitin sulfate proteoglycans. Histologic data from animals with
      experimental retinitis pigmentosa, and the existence of the hyaluronan-binding
      domain in their core proteins, indicate that these proteoglycans contribute to
      the structural link between the neural retina and retinal pigment epithelium via
      the interaction with hyaluronan, which is also abundant in the IPM. Furthermore,
      several chondroitin sulfate proteoglycans in the nerve fiber-rich layers contain
      the hyaluronan-binding domain, so it is likely that the interaction of
      proteoglycans with hyaluronan plays an important role in neural network formation
      in the central nervous system.

PMID- 12207945
TI  - The role of platelet-activating factor in the corneal response to injury.
AB  - Platelet-activating factor (PAF) is a potent bioactive lipid that is generated in
      the cornea after injury and whose actions are mediated through specific
      receptors. Studies from our laboratory have shown that PAF interactions with its
      receptor activate several transmembrane signals involved in inflammation, wound
      healing, and apoptosis. The wide variety of responses to PAF implicate this lipid
      as a central player in many responses of the cornea after a pathologic stimulus.
      An exciting facet of PAF is that it induces the expression of specific genes
      involved in the remodeling of components of the extracellular matrix, such as
      some metalloproteinases, urokinase plasminogen activator, and selective
      inhibitors of metalloproteinases. These enzymes, when overexpressed, could lead
      to corneal ulceration. Continuous exposure to PAF during prolonged inflammation
      produces increase keratocyte apoptosis and inhibition of epithelial adhesion to
      the basement membrane. As a consequence, there is a marked delay in wound
      healing, which is not countered by the actions of growth factors. In this review,
      we present data mainly from our laboratory showing actions of PAF in corneal
      epithelium in vivo and in vitro in corneal models of injury as well as in cells
      in culture. We also discuss the signal-transduction mechanisms involved in the
      different actions of PAF. A therapeutic role for PAF antagonists in blocking the
      effects of PAF is guaranteed in the future.

PMID- 12207946
TI  - Retinal ganglion cell disorders: types and treatments.

PMID- 12207947
TI  - Viagra (sildenafil citrate) and ophthalmology.
AB  - Viagra (sildenafil citrate) improves penile erections in men with erectile
      dysfunction (ED) by selectively inhibiting cGMP-specific phosphodiesterase type 5
      (PDE5), which is present in all vascular tissue. It also exerts a minor
      inhibitory action against PDE6, which is present exclusively in rod and cone
      photoreceptors. At higher doses, sildenafil causes mild and transient visual
      symptoms in a minority of patients (mainly blue tinge to vision, increased
      brightness of lights). Therefore, the effects of sildenafil on the visual system
      have been investigated in a wide variety of clinical and preclinical studies. In
      preclinical studies, sildenafil shows transient reversible effects on electrical
      response to light. In long-term toxicology studies in which animals were exposed
      to high multiples of the maximum human therapeutic dose, detailed examinations
      have revealed no adverse effects on the structure or function of the eye. The
      effects of sildenafil have been systematically investigated in visual function
      studies in volunteers and in patients with eye disease; sildenafil does not
      affect visual acuity, visual fields, and contrast sensitivity. The only definite
      effect is transient, mild impairment of color discrimination occurring around the
      time of peak plasma levels. In long-term studies, no long-term effects of
      sildenafil on the visual system have been observed. Postmarketing, sildenafil has
      been prescribed to over 15 million men with ED. Isolated examples of a variety of
      visual adverse events have been reported. No consistent pattern has emerged to
      suggest any long-term effect of sildenafil on the retina or other structures of
      the eye. Based on this experience, intermittent, short-term, partial inhibition
      of PDE5 or PDE6 by sildenafil is unlikely to induce any long-term visual change.

PMID- 12207948
TI  - Anisomycin treatment paradigm affects duration of long-term potentiation in
      slices of the amygdala.
AB  - Anisomycin has been widely used as an inhibitor of protein synthesis in studies
      on learning and memory as well as synaptic plasticity. However, its mode of
      action is complicated. Besides the inhibition of translation, this drug displays
      other effects, most prominently on mitogen-activated protein kinases. In this
      report we analyze the effects of anisomycin on the late phase of long-term
      potentiation (LTP) in amygdala slices. The late phase of LTP was evoked by high
      frequency repeated-train stimulation delivered to the external capsule and
      recorded in the lateral amygdaloid nucleus. In the no-drug condition, stimulation
      resulted in LTP lasting over 3 h without any sign of decay. Application of the
      drug 15 min before high-frequency stimulation (HFS) caused LTP decay to baseline
      within 1 h after induction. However, delivering the drug just after the first
      train of HFS resulted in LTP that returned to baseline level within 3 h since the
      onset of stimulation. These results show that the duration of the LTP in the
      amygdala depends on the anisomycin treatment paradigm and thus special caution
      should be exercised when interpreting the data obtained with this drug.

PMID- 12207949
TI  - Stress-induced preproenkephalin mRNA expression in the amygdala changes during
      early ontogeny in the rat.
AB  - Stress activates endogenous opioids that modulate nociceptive transmission.
      Exposure to a potentially infanticidal adult male rat suppresses pain-related
      behaviors in pre-weaning but not in older rats. This male-induced analgesia is
      mediated by l opioid receptors in the periaqueductal gray, a midbrain structure
      that is innervated by amygdala projections. To determine whether enkephalin, a l
      and d opioid receptor agonist, is activated by male exposure, mRNA levels of its
      precursor, preproenkephalin, were measured in subdivisions of the amygdala and
      the periaqueductal gray. In 14-day-old but not in 21-day-old rats, 5 min of male
      exposure induced analgesia to heat and increased preproenkephalin mRNA levels in
      the central nucleus of the amygdala but not in the periaqueductal gray. The
      change in the activation of enkephalinergic neurons in the central amygdala may
      contribute to the change in stress-induced analgesia during early ontogeny.

PMID- 12207950
TI  - Activity-dependent regulation of genes implicated in X-linked non-specific mental
      retardation.
AB  - X-linked forms of non-specific mental retardation are complex disorders, for
      which mutations in several genes have recently been identified. These include
      OPHN1, GDI1, PAK3, IL1RAPL, TM4SF2, FMR2 and RSK2. To investigate the mechanisms
      through which alterations of these gene products could result in cognitive
      impairment, we analyzed their expression using quantitative PCR technique in two
      in vitro models of activity-dependent gene regulation: kainate-induced seizures
      and long-term synaptic potentiation (LTP). We found that the level of expression
      of four genes, PAK3, IL1RAPL, RSK2 and TM4SF2, was significantly up-regulated
      following kainate treatment. Furthermore we observed a significant increase in
      mRNA levels of PAK3 and IL1RAPL following LTP induction. These results suggest a
      possible role for these four genes in activity-dependent brain plasticity.

PMID- 12207951
TI  - Blurring of the senses: common cues for distance perception in diverse sensory
      systems.
AB  - Distance perception is an essential task of sensory systems. Our visual systems
      effectively use binocular visual cues to determine an object's distance. Other
      visual, but monocular, cues are also available for distance perception. Visual
      contrast and image blur are two such cues [O'Shea et al., 1994. Vis. Res. 34,
      1595-1604; O'Shea et al., 1997. Perception 26, 599-612; Mather, 1997. Perception
      26, 1147-1158]. We show the effects of combining these cues using a simple
      psychophysical test. The novelty in our approach is that our exact choice of
      visual stimuli allows us to show a direct parallel between visual distance
      perception and distance perception using an entirely different sense, the
      electric sense of weakly electric fish. We discuss previous work on
      electrosensory psychophysics [von der Emde et al., 1998. Nature 395, 890-894] and
      show that cues used for electrosensory distance perception are analogous to
      visual contrast and blur. We also suggest that analogous cues are involved in
      auditory distance perception. The utilization of analogous cues implies that
      these diverse sensory systems perform similar computations for distance
      perception.

PMID- 12207952
TI  - Intracellular recordings of pontine medial gigantocellular tegmental field
      neurons in the naturally sleeping cat: behavioral state-related activity and soma
      size difference in order of recruitment.
AB  - Intracellular recordings and neurobiotin labeling of medial pontine
      gigantocellular tegmental field (m-PFTG) neurons in the undrugged, naturally
      sleeping cat were performed to establish the relationship between soma size and
      membrane potential (MP) activity before and during the onset of the rapid eye
      movement (REM) phase of sleep. Initial recordings without labeling revealed that
      recorded neurons in the m-PFTG had a tonic, sustained membrane depolarization in
      REM sleep as compared with more polarized MP levels in slow-wave sleep (S) and
      phasic depolarizations in wakefulness (W) on a more polarized MP level. In
      neurobiotin-labeled neurons, there was a strong correlation between the soma size
      of m-PFTG neurons and the 'lead time', the time of onset relative to the
      beginning of REM, of a sustained increase in membrane depolarization. Thirty-nine
      m-PFTG neurons with soma cross-sectional areas ranging from 2098 microm(2) to
      5958 microm(2) (mean value 3833.8 microm(2)) were analyzed. A majority of these m
      PFTG neurons showed an increase in membrane depolarization associated with
      depolarizing postsynaptic potentials (PSPs) and spike generation that occurred
      before electrographic signs of REM sleep onset, while the rest of the neurons
      depolarized at the beginning of or just after REM sleep onset. Our previous work
      had suggested that many of these m-PFTG neurons were output neurons to the spinal
      cord. Analysis of the onset time of sustained membrane depolarization
      (Leadtime(MP)) revealed that larger cells had a longer lead time, while analysis
      of the lead times for onset of sustained PSPs and action potentials
      (Leadtime(AP)) showed this measure not to be dependent on soma size, but to be
      rather uniform, occurring just before the onset of REM sleep. Hence recruitment
      time, defined as the difference between Leadtime(AP) and Leadtime(MP), was
      dependent on cell soma size, implying that larger neurons may take longer to
      depolarize to an MP level critical for generating sustained action potentials,
      while smaller neurons may require less time.

PMID- 12207953
TI  - Detailed localization of regulator of G protein signaling 2 messenger ribonucleic
      acid and protein in the rat brain.
AB  - Regulator of G protein signaling (RGS) proteins are a recently identified family
      of proteins which dampen G protein-coupled receptor-mediated signaling by
      accelerating the intrinsic GTPase activity of Galpha subunits of heterotrimeric G
      proteins. More than 20 different RGSs have been identified and at least 10 are
      expressed in the CNS. The present study describes in detail the localization in
      the rat brain of one member of this family, RGS2. The distribution of RGS2 mRNA
      and protein has been studied in parallel by performing in situ hybridization and
      immunoautoradiography on adjacent rat brain sections. Our localization study
      reveals that RGS2 mRNA and protein are widely expressed in the brain. Protein and
      mRNA are mostly colocalized such as in neocortex, piriform cortex, caudate
      putamen, septum, hippocampus, locus coeruleus. Some mismatches were also observed
      such as presence of mRNA but not protein in the paraventricular nucleus, the
      substantia nigra pars compacta and the red nucleus, suggesting that RGS2 protein
      is present in neuronal projections. Previous reports describing an induction of
      RGS2 mRNA in the rat striatum after psychostimulants (amphetamine, cocaine) led
      us to focus on the distribution of RGS2 in the basal ganglia circuitry. The
      absence of RGS2 mRNA and protein in the globus pallidus suggests that RGS2 would
      play its regulatory role more in the direct (striatonigral) than in the indirect
      (striatopallidal) striatal output pathway. In addition, to delineate the
      implication of RGS2 in pre- and/or postsynaptic functions in the basal ganglia,
      we performed lesions of the nigrostriatal pathway by 6-hydroxydopamine (6-OHDA)
      and striatal quinolinic acid lesions. The 6-OHDA lesion did not modify RGS2 mRNA
      or protein levels in the caudate-putamen whereas the intrastriatal quinolinic
      acid infusion caused a marked reduction of RGS2 mRNA and protein in the lesioned
      zone. These data indicate that RGS2 is predominantly expressed in intrinsic
      striatal neurons. Moreover, the absence of detectable change in RGS2 expression
      after injections of 6-OHDA suggests also that RGS2 is not primarily involved in
      the hypersensitization of postsynaptic dopamine receptors observed after lesion
      of the nigrostriatal pathway.

PMID- 12207954
TI  - Synergistic effects of corticosterone and kainic acid on neurite outgrowth in
      axotomized dorsal root ganglion.
AB  - Corticosterone is the main adrenal glucocorticoids induced by stress in rats.
      Therapeutic use of high concentration of synthetic glucocorticoids in clinical
      treatment of spinal cord injury suggests that pharmacological action of
      glucocorticoids might be beneficial for nerve repair. In this article we cultured
      axotomized rat dorsal root ganglion neurons to investigate the effects of
      corticosterone and a glutamate receptor agonist kainic acid on neurite outgrowth.
      Our results revealed a synergistic effect of corticosterone and kainic acid in
      promoting neurite outgrowth when applied as early as one and two days in vitro,
      but not effective at three and four days in vitro. In addition, applied
      corticosterone and kainic acid were neurotoxic at three and four days in vitro
      but not at one and two days in vitro. The minimal concentrations of
      corticosterone and kainic acid to be effective were 10 microM and 1 mM,
      respectively. The neurotrophic effect of corticosterone and kainic acid was
      attenuated by the receptor tyrosine kinase A (TrkA) inhibitor AG-879. Western
      blot analysis and immunocytochemical studies revealed an increase of expressions
      of both TrkA and growth-associated protein GAP-43 in dorsal root ganglion neurons
      with combined treatment of corticosterone and kainic acid. Immunocytochemistry
      showed that corticosterone+kainic acid increase nerve growth factor
      immunoreactivity in dorsal root ganglion neurites and enhance GAP-43
      immunointensity in dorsal root ganglion neurons. These results suggest that the
      neurotrophic effect of glucocorticoids on axonal regeneration might require
      facilitation of excitatory stimulation at an early stage of nerve injury, and
      nerve growth factor may mediate a growth signaling to accomplish the effect.

PMID- 12207955
TI  - Effects of glucose and 2-deoxyglucose on memory formation in the chick:
      interaction with beta(3)-adrenoceptor agonists.
AB  - Consolidation of a weakly reinforced memory that would otherwise fade after 30
      min can be achieved by central or peripheral injection of the selective beta(3)
      adrenoceptor agonist CL316243 as well as the beta(2)-adrenoceptor agonist
      zinterol and the alpha(1)-adrenoceptor antagonist prazosin in the day-old chick.
      The effect of the beta(3)-adrenoceptor agonist is mimicked by peripheral or
      central injection of glucose that is effective in enhancing memory from 25 min
      before to 25 min after training. Glucose uptake into various cell types has been
      described following activation of beta(3)-adrenoceptors and in this paper we
      demonstrate that activation of beta(3)-adrenoceptors by CL316243 facilitates the
      effect of a dose of glucose that does not normally enhance memory, whereas a
      beta(2)-adrenoceptor agonist and an alpha(1)-adrenoceptor antagonist have no
      effect. Administration of the glucose uptake inhibitor 2-deoxyglucose prevented
      the consolidation of strongly reinforced training. The beta(3)-adrenoceptor
      agonist facilitated the effect of a non-amnestic dose of 2-deoxyglucose to
      inhibit memory. There are two time periods relative to the learning trial where
      memory is vulnerable to interference by centrally administered 2-deoxyglucose:
      one related to short-term memory and one at the time of consolidation into long
      term memory. Peripheral injection of 2-deoxyglucose is only effective at the time
      of consolidation. The action of the beta(3)-adrenoceptor agonist to facilitate
      the action of 2-deoxyglucose only occurs at the time of consolidation. We suggest
      that a noradrenergic agonist acting at beta(3)-adrenoceptors enhances memory
      formation by facilitation of glucose uptake at the time of memory consolidation.
      This may represent a novel mechanism that would be beneficial for developing
      compounds for the facilitation of memory in diseases with cognitive deficits.

PMID- 12207956
TI  - Cyclic AMP differentially regulates the expression of fibroblast growth factor
      and epidermal growth factor receptors in cultured cortical astroglia.
AB  - Fibroblast growth factor (FGF)-2 and transforming growth factor alpha (TGFalpha)
      promote astroglial proliferation during brain development and reactive processes.
      The mitogenic potential of both growth factors is attenuated by increasing
      intracellular cAMP levels, an effect currently assumed to depend on the
      inhibition of the mitogen-activated protein kinase cascade. In the present study,
      we sought to determine whether cAMP interferes with the mitogenic potential of
      FGF-2 and TGFalpha on astroglia by affecting the expression of respective growth
      factor receptors. Treatment of highly enriched cultures of cortical astrocytes
      with dibutyryl cAMP accelerated the TGFalpha-induced internalization and
      subsequent functional inactivation of epidermal growth factor (EGF) receptor by
      transiently inhibiting EGF receptor mRNA synthesis. In apparent contrast, both
      short- and long-term activation of cAMP-dependent signaling pathways robustly
      promoted the expression of FGF receptors 1 and 2, whereas expression levels of
      FGF receptor 3 remained unaffected. Moreover, elevation of intracellular cAMP
      levels did not prevent translocation of FGF receptor 1 to the cell nucleus, a
      mechanism thought to be essential for FGF-2-induced cell proliferation. We
      propose that cAMP controls the mitogenic effects of TGFalpha and FGF-2 on
      astroglial cells by distinctly different mechanisms. Whereas cAMP seems to
      interfere with the mitogenic effects of TGFalpha on astroglial cells by affecting
      both the expression level and signaling of the EGF receptor, the modulatory
      effects of cAMP on FGF-2-induced astroglial proliferation seem to solely result
      from an inhibition of FGF receptor-activated signaling pathways.

PMID- 12207958
TI  - Behavioural and immunohistochemical changes following supranigral administration
      of sonic hedgehog in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-treated common
      marmosets.
AB  - Sonic hedgehog (SHH) has trophic actions on dopaminergic cell cultures and
      protects them from MPP(+) toxicity but its in vivo actions have not been
      explored. We now investigate the effects of unilateral supranigral administration
      of SHH on nigro-striatal function in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine
      treated common marmosets. SHH (0.1 or 1.0 microg) or vehicle was stereotaxically
      injected into the region of the right substantia nigra twice with an interval of
      5 weeks between administrations. The first or second administration of low dose
      SHH (0.1 microg) did not significantly improve motor disability or locomotor
      activity compared to time-matched vehicle-treated animals. There was, however, an
      approximately 30% improvement in both motor disability and locomotor activity
      following the first administration of high dose SHH (1.0 microg). No further
      improvements occurred following the second high dose SHH treatment. Acute oral
      administration of L-3,4-dihydroxyphenylalanine (L-DOPA) produced a smaller
      increase in locomotor activity and greater reversal of motor disability in
      animals treated with SHH than occurred in vehicle-treated common marmosets. In
      the substantia nigra pars compacta, ipsilateral to SHH administration, the number
      of tyrosine hydroxylase-positive neurones was increased by 21% (P > 0.05) and 57%
      (P < 0.05) in low and high dose SHH groups respectively compared to the untreated
      contralateral hemisphere. There was no difference in the number of glial
      fibrillary acidic protein-positive cells. SHH may improve nigro-striatal function
      by restoring tyrosine hydroxylase positivity. This is reflected by an improvement
      in basal disability and a reduction in the lesion-induced response to L-DOPA.

PMID- 12207957
TI  - Rivastigmine antagonizes deficits in prepulse inhibition induced by selective
      immunolesioning of cholinergic neurons in nucleus basalis magnocellularis.
AB  - Impairments of cortical cholinergic inputs from the nucleus basalis
      magnocellularis fundamentally alter information processing and attentional
      function, thereby advancing the severity of psychopathology in major
      neuropsychiatric disorders. It was previously shown in adult rats that bilateral
      192 IgG saporin-induced selective immunolesioning of the cholinergic neurons in
      the nucleus basalis produces pronounced and long-lasting deficits in sensorimotor
      gating measured by prepulse inhibition of the startle reflex. This behavioral
      paradigm is considered a valid model of sensorimotor gating deficits in the
      psychotic spectrum and efforts to analyze the significance of the cholinergic
      basal forebrain in this context are of great interest. In the present study the
      predictive value of the selective cholinergic immunolesioning model was tested by
      examining the ability of the cholinesterase inhibitor rivastigmine to restore
      prepulse inhibition in immunolesioned rats. We report here a pronounced restoring
      effect of acute (0.75 or 1.5 mg/kg s.c.) as well as repeated (0.75 mg/kg s.c.
      b.i.d., for 10 days) treatment with rivastigmine in this model of disrupted
      prepulse inhibition. Intra-nucleus basalis magnocellularis infusions of 192 IgG
      saporin resulted in extensive loss of basal-cortical cholinergic neurons as shown
      by the marked decrease in basal telencephalic choline acetyltransferase
      immunopositive neurons and cortical choline acetyltransferase activity. In this
      condition, rivastigmine was found to significantly increase cortical
      acetylcholine extracellular levels in lesioned animals measured by in vivo
      microdialysis. Taken together, our results strengthen the proposal that the
      nucleus basalis represents a critical station of the startle gating circuitry. In
      addition, our findings strongly indicate that even after dramatic decrease of
      cholinergic neurons, inhibition of acetylcholinesterase restores the cholinergic
      synaptic function to a point approaching normalization of experimentally induced
      psychopathology.

PMID- 12207959
TI  - L-citrulline immunostaining identifies nitric oxide production sites within
      neurons.
AB  - The cellular and subcellular localization of L-citrulline was analyzed in the
      adult rat brain and compared with that of traditional markers for the presence of
      nitric oxide synthase. Light, transmission electron, and confocal laser scanning
      microscopy were used to study tissue sections processed for immunocytochemistry
      employing a monoclonal antibody against L-citrulline or polyclonal anti-neuronal
      nitric oxide synthase sera, and double immunofluorescence to detect neuronal
      nitric oxide synthase and L-citrulline co-localization. The results demonstrate
      that the same CNS regions and cell types are labeled by neuronal nitric oxide
      synthase polyclonal antisera and L-citrulline monoclonal antibodies, using both
      immunocytochemistry and immunofluorescence. Short-term pretreatment with a nitric
      oxide synthase inhibitor reduces L-citrulline immunostaining, but does not affect
      neuronal nitric oxide synthase immunoreactivity. In the vestibular brainstem,
      double immunofluorescence studies show that many, but not all, neuronal nitric
      oxide synthase-positive cells co-express L-citrulline, and that local
      intracellular patches of intense L-citrulline accumulation are present in some
      neurons. Conversely, all L-citrulline-labeled neurons co-express neuronal nitric
      oxide synthase. Cells expressing neuronal nitric oxide synthase alone are
      interpreted as neurons with the potential to produce nitric oxide under other
      stimulus conditions, and the subcellular foci of enhanced L-citrulline staining
      are viewed as intracellular sites of nitric oxide production. This interpretation
      is supported by ultrastructural observations of subcellular foci with enhanced L
      citrulline and/or neuronal nitric oxide synthase staining that are located
      primarily at postsynaptic densities and portions of the endoplasmic reticulum. We
      conclude that nitric oxide is produced and released at focal sites within neurons
      that are identifiable using L-citrulline as a marker.

PMID- 12207960
TI  - GABAergic and glutamatergic terminals differentially influence the organization
      of GABAergic synapses in rat cerebellar granule cells in vitro.
AB  - Synapse formation in CNS neurons requires appropriate sorting and clustering of
      neurotransmitter receptors and associated proteins at postsynaptic sites. In
      GABAergic synapses, clustering of GABA(A) receptors requires gephyrin, but it is
      not known whether presynaptic signals are also involved in this process. To
      investigate this issue, we analyzed the subcellular distribution of GABA(A)
      receptors and gephyrin in primary cultures of cerebellar granule cells, by
      comparing cells receiving GABAergic input with cells devoid of such afferents.
      Using immunofluorescence staining, we show that the GABA(A) receptor alpha1 and
      gamma2 subunit, but not alpha6 or delta subunit, form clusters co-localized with
      gephyrin in granule cell neurites, irrespective of the presence of GABAergic
      axons. GABAergic terminals typically were surrounded by groups of gephyrin
      clusters, pointing to the presence of multiple synaptic sites. In contrast, in
      neurites devoid of GABAergic input, gephyrin clusters were distributed at random
      and apposed to glutamatergic terminals, suggesting the formation of mismatched
      synapses. Both populations of gephyrin clusters were co-localized with GABA(A)
      receptor subunits, indicating that these proteins are associated also in non
      GABAergic synapses. To determine whether signaling mediated by GABA(A) receptors
      is required for the formation of appropriately matched gephyrin clusters,
      cultures were treated chronically with bicuculline, or with either muscimol or
      4,5,6,7-tetrahydroisoxazolo[5,4-c]pyridin-3-ol. All these treatments failed to
      influence the distribution of gephyrin clusters. We conclude that although
      GABAergic presynaptic terminals have a preponderant influence on the distribution
      of gephyrin clusters in dendrites of cerebellar granule cells, GABA transmission
      is dispensable for postsynaptic clustering of gephyrin and GABA(A) receptors and
      for the formation of appropriately matched GABAergic synapses.

PMID- 12207961
TI  - Gene expression in rat vestibular and reticular structures during and after space
      flight.
AB  - Space flight produces profound changes of neuronal activity in the mammalian
      vestibular and reticular systems, affecting postural and motor functions. These
      changes are compensated over time by plastic alterations in the brain. Immediate
      early genes (IEGs) are useful indicators of both activity changes and neuronal
      plasticity. We studied the expression of two IEG protein products [Fos and Fos
      related antigens (FRAs)] with different cell persistence times (hours and days,
      respectively) to identify brainstem vestibular and reticular structures involved
      in adaptation to microgravity and readaptation to 1 G (gravity) during the NASA
      Neurolab Mission (STS-90). IEG protein expression in flight animals was compared
      to that of ground controls using Fisher 344 rats killed 1 and 12 days after
      launch and 1 and 14 days after landing. An increase in the number of Fos-protein
      positive cells in vestibular (especially medial and spinal) regions was observed
      1 day after launch and 1 day after landing. Fos-positive cell numbers were no
      different from controls 12 days after launch or 14 days after landing. No G
      related changes in IEG expression were observed in the lateral vestibular
      nucleus. The pattern of FRA protein expression was generally similar to that of
      Fos, except at 1 day after landing, when FRA-expressing cells were observed
      throughout the whole spinal vestibular nucleus, but only in the caudal part of
      the medial vestibular nucleus. Fos expression was found throughout the entire
      medial vestibular nucleus at this time. While both Fos and FRA expression
      patterns may reflect the increased G force experienced during take-off and
      landing, the Fos pattern may additionally reflect recent rebound episodes of
      rapid eye movement (REM) sleep following forced wakefulness, especially after
      landing. Pontine activity sources producing rhythmic discharges of vestibulo
      oculomotor neurons during REM sleep could substitute for labyrinthine signals
      after exposure to microgravity, contributing to activity-related plastic changes
      leading to G readaptation. Reticular structures exhibited a contrasting pattern
      of changes in the numbers of Fos- and FRA-positive cells suggestive of a major
      influence from proprioceptive inputs, and plastic re-weighting of inputs after
      landing. Asymmetric induction of Fos and FRAs observed in some vestibular nuclei
      1 day after landing suggests that activity asymmetries between bilateral otolith
      organs, their primary labyrinthine afferents, and vestibular nuclei may become
      unmasked during flight.

PMID- 12207962
TI  - A novel role of pedunculopontine tegmental kainate receptors: a mechanism of
      rapid eye movement sleep generation in the rat.
AB  - Considerable evidence suggests that pedunculopontine tegmental cholinergic cells
      are critically involved in normal regulation of rapid eye movement sleep. The
      major excitatory input to the cholinergic cell compartment of the
      pedunculopontine tegmentum arises from glutamatergic neurons in the pontine
      reticular formation. Immunohistochemical studies reveal that both ionotropic and
      metabotropic receptors are expressed in pedunculopontine tegmental cells. This
      study aimed to identify the role of endogenous glutamate and its specific
      receptors in the pedunculopontine tegmentum in the regulation of physiological
      rapid eye movement sleep. To identify this physiological rapid eye movement sleep
      inducing glutamate receptor(s) in the pedunculopontine tegmental cholinergic cell
      compartment, specific receptors were blocked differentially by local
      microinjection of selective glutamate receptor antagonists into the
      pedunculopontine tegmental cholinergic cell compartment while quantifying the
      effects on rapid eye movement sleep in freely moving chronically instrumented
      rats. By comparing the alterations in the patterns of rapid eye movement sleep
      following injections of control vehicle and selective glutamate receptor
      antagonists, contributions made by each receptor subtype in rapid eye movement
      sleep were evaluated. The results demonstrate that when kainate receptors were
      blocked by local microinjection of a kainate receptor selective antagonist,
      spontaneous rapid eye movement sleep was completely absent for the first 2 h, and
      for the next 2 h the total percentage of rapid eye movement sleep was
      significantly less compared to the control values. In contrast, when N-methyl-D
      aspartate, alpha-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid, groups I,
      II, and III metabotropic receptors were blocked, total percentages of rapid eye
      movement sleep did not change compared to the control values. These findings
      suggest, for the first time, that the activation of kainate receptors within the
      cholinergic cell compartment of the pedunculopontine tegmentum is a critical step
      for the regulation of normal rapid eye movement sleep in the freely moving rat.
      The results also suggest that the different types of glutamate receptors within a
      small part of the brainstem may be involved in different types of physiological
      functions.

PMID- 12207963
TI  - Changes in cortical and cerebellar bcl-2 mRNA levels in the developing
      hydrocephalic rat (LEW-HYR) as measured by a real time quantified RT-PCR.
AB  - In order to evaluate the appearance of brain bcl-2 during development of the
      hydrocephalus, we measured levels of bcl-2 mRNA in the cortex and cerebellum of
      congenital hydrocephalic rats (LEW-HYR) at 1 and 2 weeks after birth using the
      quantified reverse transcriptase-polymerase chain reaction (RT-PCR) with TaqMan
      fluorogenic detection system. Normal and hydrocephalic siblings were killed 7 and
      14 days after birth, and their cortices and cerebella were homogenized with the
      Isogen-chloroform mixtured solution. By means of the RT-PCR with genetic
      analyzer, the sequence of bcl-2 mRNA detected in the LEW-HYR was identified to be
      the same as that of the registered rat brain (L14680). During the development of
      normal siblings of LEW-HYR, the levels of bcl-2 mRNA detected in the cortex and
      cerebellum 7 days after birth were significantly higher than those seen on day 14
      after birth. In the hydrocephalic rats, however, these levels were not
      significantly different during development. On days 7 and 14 after birth, the
      cortical levels of bcl-2 mRNA detected in the hydrocephalic rats were
      significantly higher than those in normal rats. In the cerebellum, these levels
      in the hydrocephalic rats were higher, but not significantly, than those of
      normal rats. These results indicate that the significant appearance of bcl-2 mRNA
      in the developing normal rat brain is related to sprouting and to the diminished
      number of neurons, whereas the significant increase of bcl-2 levels seen in the
      developing hydrocephalic rats is indicative of an excess activity of glutamate
      neurons in cerebral cortex and the protection of neurons from cell death induced
      by cerebral ventricular dilatation in the cortex after bcl-2 levels.

PMID- 12207964
TI  - A detailed mapping of the histamine H(3) receptor and its gene transcripts in rat
      brain.
AB  - The detailed distribution of histamine H(3) receptor mRNAs in rat brain was
      analyzed by in situ hybridization using a 33P-labelled riboprobe and was combined
      for the first time with the detailed autoradiographic distribution of the
      receptor determined in the same animals with [(125)I]iodoproxyfan, a selective
      radioligand. The signals generated on adjacent brain sections by each probe were
      quantified and/or rated and were compared in order to identify neuronal
      populations expressing the receptor. In addition, the cellular localization of
      the transcripts within various brain structures was analyzed in sections dipped
      in a photographic emulsion. In the cerebral cortex, the strong mRNA expression in
      intermediate and deep layers indicates the presence of H(3) receptors on several
      types of neurons. The binding is dense except in layer V, suggesting that H(3)
      receptors are located on granule cells and apical dendrites of pyramidal cells.
      In addition to their localization on monoaminergic afferents, the dense binding
      in layer IV and strong mRNA expression in thalamic nuclei suggest the presence of
      heteroreceptors on thalamocortical projections. In the hippocampus, the strong
      mRNA expression but low binding in pyramidal layers of the CA1 and ventral CA3
      fields suggest that H(3) receptors are abundant on efferent projections of
      pyramidal cells. In the dentate gyrus, some binding sites in the molecular layer
      may correspond to H(3) receptors synthesized in granule cells and coexpressed
      with H(1) and H(2) receptors in their dendrites. In the basal ganglia, H(3)
      receptors are highly expressed in the striatal complex and olfactory tubercles
      but not in islands of Calleja. Some of the striatal binding sites may correspond
      to presynaptic receptors present on afferents. The mRNAs in cortical layer V may
      encode for heteroreceptors on corticostriatal neurons. The presence of mRNAs in
      the substantia nigra pars compacta suggests that H(3) receptors are located upon
      nigrostriatal afferents. However, the absence of any signal in the ventral
      tegmental area indicates that some but not all dopaminergic neurons express H(3)
      receptors. In addition, the homogeneous mRNA expression within the caudate
      putamen and nucleus accumbens suggests that many striatal H(3) receptors are
      present on medium-sized, spiny projection neurons of both the direct and indirect
      movement pathways. In agreement, a dense binding, but low mRNA expression, is
      observed in external and internal pallidum and in substantia nigra pars
      reticulata. In the amygdala, the dense binding and mRNA expression indicate the
      presence of receptors on both afferents and projections. In the thalamus, the
      binding in some association nuclei may correspond to receptors present on neurons
      emanating from the deep cortical layers that strongly express the mRNAs, as well
      as receptors on the visual systems. However, the low binding and high mRNA
      expression in most nuclei indicate that many receptors are present upon thalamic
      projections. In the hypothalamus, the mRNA expression parallels the density of
      binding sites and is the highest in the tuberomammillary nucleus. Further
      investigation is needed to know if the dense binding and mRNA expression observed
      in other nuclei such as the paraventricular, ventromedial and medial tuberal
      nuclei correspond to pre- and/or postsynaptic receptors. mRNAs are also observed
      in several areas projecting to the tuberomammillary nucleus, such as the
      ventrolateral preoptic nucleus. In the lower brainstem, the high mRNA expression
      and very low binding in the locus coeruleus and raphe nuclei indicate that
      presynaptic rather than somatodendritic receptors regulate noradrenaline and
      serotonin release, respectively. A similar pattern in vestibular nuclei suggests
      that receptors located on projections account for the anti-vertigo properties of
      H(3) receptor antagonists. In the cerebellum, binding is hardly detectable but a
      strong mRNA expression is found in most, if not all, Purkinje cells as well as in
      several central cerebellar nuclei, suggesting the presence of H(3) receptors on
      efferent projections. The present study reports the first detailed quantification
      and/or rating of H(3) receptor mRNAs in the brain. The comparison, performed in
      the same animals, with the distribution of the H(3) receptor protein provides
      evidence for the presence of H(3) receptors on many neuronal perikarya, dendrites
      and projections. Although some localizations, mainly as auto- or heteroreceptors,
      are consistent with previous functional studies, the physiological role, if any,
      of most of these presynaptic or postsynaptic receptors remains to be established.

PMID- 12207965
TI  - Effects of neonatal handling on basal and stress-induced monoamine levels in the
      male and female rat brain.
AB  - Neonatal handling has pervasive effects on the rat brain leading to increased
      ability to cope with and adapt to stressful stimuli. We determined the effects of
      neonatal handling on the dopaminergic and serotonergic system, in the male and
      female rat brain, under basal conditions before and after puberty and after short
      and long-term forced swimming stress. Exposure of animals to neonatal handling
      resulted in sex-dependent changes in the concentration and turnover of monoamines
      in the different brain areas. In the prepubertal brain, the effect of neonatal
      handling was manifested as an increase in dopamine turnover in the females,
      particularly in the hypothalamus, an increase in serotonin levels and a decrease
      in its turnover in all three brain regions examined of both males and females.
      Certain of the handling-induced effects observed in the prepubertal brain were
      reversed in the postpubertal animals. Thus, in the postpubertal brain, the
      handling-induced changes in serotonin levels and its turnover observed in both
      sexes before puberty were abolished. On the other hand, the handling-induced
      increase in hypothalamic dopamine turnover was maintained. After exposure to
      short-term stress, the effect of handling was manifested on one hand as decreased
      striatal dopamine levels in the females, and decreased dopamine turnover in the
      hypothalamus of both males and females, and on the other, as increased serotonin
      levels in the hypothalamus. After exposure to long-term stress, handled females
      had decreased dopamine turnover in the hypothalamus and the striatum, but there
      was no effect of handling on the serotonergic system. Our results provide some
      neurobiological evidence supporting the determinant role of the mother-infant
      relationship in the development of psychopathology. Neonatal handling, which
      modifies normal mother-pup interactions, results in alterations in brain
      dopaminergic and serotonergic systems, both of which are involved in the
      etiopathogenesis of major psychoses. Exposure to either short- or long-term
      stress in adult life results in sex-dependent changes in brain monoamines, which
      are affected by handling thus making coping more efficient and rendering the
      stressful stimulus less noxious.

PMID- 12207966
TI  - Presynaptic modulation of GABAergic inhibition by GABA(B) receptors in the rat's
      inferior colliculus.
AB  - Whole-cell patch clamp recordings were made from neurons in a brain slice
      preparation of the inferior colliculus in 11-15-day-old rat pups. Synaptic
      responses were elicited by applying a current pulse to the lateral lemniscus just
      below the central nucleus of the inferior colliculus. To examine GABAergic
      inhibition in the inferior colliculus all excitatory postsynaptic potentials and
      glycinergic inhibitory postsynaptic potentials were blocked by bath application
      of their respective antagonists and the contribution of GABA(B) receptors was
      determined for the remaining inhibitory postsynaptic potentials. For most cells
      the isolated inhibitory postsynaptic potential was completely blocked by the
      GABA(A) receptor antagonist, bicuculline, but was unaffected by the GABA(B)
      receptor antagonist, phaclofen. The GABA(B) receptor agonist, baclofen (10-20
      microM), decreased the amplitude of the inhibitory postsynaptic potentials. This
      effect was completely blocked by phaclofen. Baclofen did not increase the cell
      membrane conductance or alter the rate of firing produced by depolarization of
      the cell membrane. In contrast, muscimol, a GABA(A) receptor agonist, greatly
      increased membrane conductance and lowered the firing rate produced by
      depolarization. Our results indicate that GABAergic inhibition in the auditory
      midbrain can be reduced by the activation of GABA(B) receptors and suggest that
      the effects are presynaptic.

PMID- 12207967
TI  - Physiological and pathological caspase cleavage of the neuronal RasGEF GRASP-1 as
      detected using a cleavage site-specific antibody.
AB  - Caspases are proteases involved in various physiological and pathological
      processes in the nervous system, including development and pathogenesis. GRASP-1
      is a recently identified neuronal substrate of caspase-3-subfamily caspases. It
      is a Ras-guanine nucleotide exchange factor (RasGEF) that interacts with the
      glutamate receptor interacting protein (GRIP). This alpha-amino-3-hydroxy-5
      methyl-4-isoxazole propionate (AMPA) receptor/GRIP protein complex has been
      proposed to be involved in AMPA receptor synaptic targeting. The caspase-3
      cleavage of GRASP-1 separates the N-terminal RasGEF catalytic domain from the C
      terminal GRIP-interacting region, potentially disrupting regulation of the RasGEF
      activity by GRIP. To examine the regulation and regional distribution of the
      caspase-3 cleavage of GRASP-1 in vivo, we generated a cleavage site-specific
      antibody, termed CGP, against the cleaved N-terminal fragment of GRASP-1. Using
      this antibody, we have examined the caspase cleavage of GRASP-1 during postnatal
      development and following ischemia in mice. We found that caspase cleavage of
      GRASP-1 occurs in specific brain regions in a time-dependent manner during
      development and ischemia. This data provides an important account of the brain
      areas that might require caspase-3 activity in postnatal development and ischemic
      damage, which has not been documented. It also demonstrates that the CGP antibody
      is a powerful tool for studying neuronal activity of the caspase-3-subfamily
      caspases in vivo.

PMID- 12207968
TI  - Prolactin-releasing peptide (PrRP) promotes awakening and suppresses absence
      seizures.
AB  - Prolactin releasing peptide (PrRP) is a recently identified neuropeptide that
      stimulates prolactin release from pituitary cells. The presence of its receptor
      outside the hypothalamic-pituitary axis suggests that it may have other
      functions. We present here evidence that PrRP can modulate the activity of the
      reticular thalamic nucleus, a brain region with prominent PrRP receptor
      expression that is critical for sleep regulation and the formation of non
      convulsive absence seizures. Intracerebroventricular injection of PrRP (1-10
      nmol) into sleeping animals significantly suppresses sleep oscillations and
      promotes rapid and prolonged awakening. Higher concentrations of PrRP (10-100
      nmol) similarly suppress spike wave discharges seen during absence seizures in
      genetic absence epilepsy rats from Strasbourg, an animal model for this disorder.
      In concordance with these findings, PrRP suppressed evoked oscillatory burst
      activity in reticular thalamic slices in vitro. These results indicate that PrRP
      modulates reticular thalamic function and that activation of its receptor
      provides a new target for therapies directed at sleep disorders and absence
      seizures.

PMID- 12207969
TI  - Firing pattern modulation by oscillatory input in supragranular pyramidal
      neurons.
AB  - Neocortical neurons in vivo receive periodic stimuli due to feedforward input
      from the periphery as well as local cellular and circuit properties. In order to
      understand how neurons process such information, the responses of neurons to
      periodic sine wave current stimuli of varying frequencies and amplitudes were
      investigated. Sine wave stimuli were injected into pyramidal cells of young adult
      ferret visual cortical slices in vitro using sharp microelectrodes. To simulate
      higher resting membrane potentials observed in vivo a slight depolarizing current
      was injected to bring the neuron just to threshold. Initially, neurons discharged
      at least one action potential per sine wave cycle, but as the frequency was
      increased, a point was reached where this one-to-one responsiveness was lost.
      This critical frequency was dependent upon the injected sine wave amplitude and
      the magnitude of the underlying steady-state depolarization, and was correlated
      with spike width. Larger steady-state depolarizations and thinner action
      potentials corresponded to higher critical frequencies. Thus, when a neuron was
      very active it could respond in a one-to-one fashion over a greater range of
      frequencies than with the smallest DC offset. The results suggest that the
      frequency-following characteristics of individual cortical neurons can be
      modulated by the activity state of the neuron itself.

PMID- 12207970
TI  - Biochemical and immunocytochemical characterization of calsenilin in mouse brain.
AB  - Mutations in the presenilin 1 and 2 genes cause the majority of early onset
      familial forms of Alzheimer's disease. Here we describe the biochemical and
      immunohistochemical characterization of calsenilin, a novel calcium binding
      protein that we have previously shown to interact with presenilins 1 and 2, in
      mouse brain. The co-immunoprecipitation of endogenous calsenilin and presenilin 1
      demonstrates that these proteins are physiologic binding partners. Although
      calsenilin has been predicted to be a soluble protein, we have found that the
      majority of it is tightly associated with the cytoplasmic face of intracellular
      membranes and that it can only be dissociated using harsh treatments such as
      urea. In addition, we have demonstrated that calsenilin is a developmentally
      regulated protein that is mainly present in the brain, where it localizes to both
      the hippocampus and cerebellum. Calsenilin staining co-localized with the
      somatodendritic marker microtubule-associated protein-2 primarily in the granular
      cell layer of the cerebellum, indicating that calsenilin expression is primarily
      neuronal. In primary cultured neurons, calsenilin immunoreactivity was observed
      in cell bodies as well as in some neuronal processes. Co-localization experiments
      using specific axonal and dendritic markers indicate that these processes were
      mainly axonal in nature, although a smaller subset of dendrites also appears to
      contain calsenilin. In summary, we have established that calsenilin and
      presenilin 1 can interact at physiologic levels, and that calsenilin is a
      developmentally regulated protein that is expressed primarily in the cerebellum
      and hippocampus. Although calsenilin is a soluble protein, it is tightly
      associated with the membrane. Finally, the expression pattern of calsenilin,
      which is similar to that of the presenilin(s), suggests that the common locations
      of these two proteins provide an opportunity for physical interaction in vivo.

PMID- 12207971
TI  - Characterization of neuronal dystrophy induced by fibrillar amyloid beta:
      implications for Alzheimer's disease.
AB  - Amyloid deposition, neuronal dystrophy and synaptic loss are characteristic
      pathological features of Alzheimer's disease (AD). We have used cortical neuronal
      cultures to assess the dystrophic effect of fibrillar amyloid beta (Abeta) and
      its relationship with neurotoxicity and synaptic loss. Treatment with fibrillar
      Abeta led to the development of neuritic dystrophy in the majority of the neurons
      present in the culture. Morphometric analysis and viability assays showed that
      neuronal dystrophy appeared significantly earlier and at lower Abeta
      concentrations than neurotoxicity, suggesting that both effects are generated
      independently by different cellular mechanisms. The development of dystrophic
      features required Abeta fibril formation and did not depend on the presence of
      the RHDS adhesive domain in the sequence of Abeta. Finally, a dramatic reduction
      in the density of synaptophysin immunoreactivity was closely associated with
      dystrophic changes in viable neurons. These results suggest that aberrant plastic
      changes and loss of synaptic integrity induced by fibrillar Abeta may play a
      significant role in the development of AD pathology.

PMID- 12207972
TI  - Neurobiology of ammonia.
AB  - Hyperammonemia resulting from inherited urea cycle enzyme deficiencies or liver
      failure results in severe central nervous system dysfunction including brain
      edema, convulsions and coma. Neuropathologic evaluation in these disorders
      reveals characteristic alterations of astrocyte morphology ranging from cell
      swelling (acute hyperammonemia) to Alzheimer Type II astrocytosis (chronic
      hyperammonemia). Having no effective urea cycle, brain relies on glutamine
      synthesis for the removal of excess ammonia and the enzyme responsible, glutamine
      synthetase, has a predominantly astrocytic localization. Accumulation of ammonia
      in brain results in a redistribution of cerebral blood flow and metabolism from
      cortical to sub-cortical structures. In addition to changes in astrocyte
      morphology, increased brain ammonia concentrations result in alterations in
      expression of key astrocyte proteins including glial fibrillary acidic protein,
      glutamate and glycine transporters and "peripheral-type" (mitochondrial)
      benzodiazepine receptors. Such changes result in alterations of astrocytic volume
      and increased extracellular concentrations of excitatory and inhibitory
      substances. In addition, the ammonium ion has direct effects on excitatory
      inhibitory transmission via distinct mechanisms involving cellular chloride
      extrusion and postsynaptic receptor function. Acute ammonia exposure leads to
      activation of NMDA receptors and their signal transduction pathways. Chronic
      hyperammonemia also results in increased concentrations of neuroactive L
      tryptophan metabolites including serotonin and quinolinic acid. Therapy in
      hyperammonemic syndromes continues to rely on ammonia-lowering strategies via
      peripheral mechanisms (reduction of ammonia production in the gastrointestinal
      tract, increased ammonia removal by muscle).

PMID- 12207973
TI  - The neurophysiology of concussion.
AB  - Cerebral concussion is both the most common and most puzzling type of traumatic
      brain injury (TBI). It is normally produced by acceleration (or deceleration) of
      the head and is characterized by a sudden brief impairment of consciousness,
      paralysis of reflex activity and loss of memory. It has long been acknowledged
      that one of the most worthwhile techniques for studying the acute pathophysiology
      of concussion is by the recording of neurophysiological activity such as the
      electroencephalogram (EEG) and sensory evoked potentials (EPs) from experimental
      animals. In the first parts of this review, the majority of such studies
      conducted during the past half century are critically reviewed. When potential
      methodological flaws and limitations such as anesthetic protocols, infliction of
      multiple blows and delay in onset of recordings were taken into account, two
      general principles could be adduced. First, the immediate post-concussive EEG was
      excitatory or epileptiform in nature. Second, the cortical EP waveform was
      totally lost during this period. In the second parts of this review, five
      theories of concussion which have been prominent during the past century are
      summarized and supportive evidence assessed. These are the vascular, reticular,
      centripetal, pontine cholinergic and convulsive hypotheses. It is concluded that
      only the convulsive theory is readily compatible with the neurophysiological data
      and can provide a totally viable explanation for concussion. The chief tenet of
      the convulsive theory is that since the symptoms of concussion bear a strong
      resemblance to those of a generalized epileptic seizure, then it is a reasonable
      assumption that similar pathobiological processes underlie them both. Further, it
      is demonstrated that EPs and EEGs recorded acutely following concussive trauma
      are indeed the same or similar to those obtained following the induction of a
      state of generalized seizure activity (GSA). According to the present incarnation
      of the convulsive theory, the energy imparted to the brain by the sudden
      mechanical loading of the head may generate turbulent rotatory and other
      movements of the cerebral hemispheres and so increase the chances of a tissue
      deforming collision or impact between the cortex and the boney walls of the
      skull. In this conception, loss of consciousness is not orchestrated by
      disruption or interference with the function of the brainstem reticular
      activating system. Rather, it is due to functional deafferentation of the cortex
      as a consequence of diffuse mechanically-induced depolarization and synchronized
      discharge of cortical neurons. A convulsive theory can also explain traumatic
      amnesia, autonomic disturbances and the miscellaneous collection of symptoms of
      the post-concussion syndrome more adequately than any of its rivals. In addition,
      the symptoms of minor concussion (a.k.a. being stunned, dinged, or dazed) are
      often strikingly similar to minor epilepsy such as petit mal. The relevance of
      the convulsive theory to a number of associated problems is also discussed. These
      include the relationship between concussion and more serious types of closed head
      injury, the utility of animal models of severe brain trauma, the etiology of the
      cognitive deficits which may linger long after a concussive injury, the use of
      concussive (captive bolt) techniques to stun farm animals prior to slaughter and
      the question of why some animals (such as the woodpecker) can tolerate massive
      accelerative forces without being knocked out.

PMID- 12207974
TI  - Depth from subjective color and apparent motion.
AB  - We report that color and depth, as well as form, are recovered in tandem with
      seeing motion. The stimulus, consisting of multiple frames, was designed to keep
      all aspects, except color, of the binocular images identical. In still view,
      rivalry occurs due to the unmatched color of some corresponding image elements in
      the two eyes. When frames--created by translating color assignments and nothing
      else--are rapidly cycled, a colored object is seen moving in depth. In natural
      scenes the same mechanisms may be used to reconstruct depth, color, and form of
      hidden objects so that they can be seen as if in plain view.

PMID- 12207975
TI  - Spatial-frequency characteristics of letter identification in central and
      peripheral vision.
AB  - Spatial-frequency characteristics of letter identification are much better
      understood in the fovea than in the periphery. The purpose of this study was to
      compare the spatial-frequency characteristics of letter identification in central
      and peripheral vision. We measured contrast thresholds for identifying single,
      Times-Roman lower-case letters that were spatially band-pass filtered. Each of
      the 26 letters was digitally filtered with a set of nine cosine log filters, with
      peak object spatial frequencies ranging from 0.63 to 10 c/letter, in half-octave
      steps. Bandwidth of the filters was 1 octave. Three observers with normal vision
      were each tested monocularly at the fovea, and at 5 degrees and 10 degrees in the
      inferior visual field. Letter sizes were 0.2, 0.4 and 0.6 log units larger than
      high contrast, unfiltered acuity letters. Plots of contrast sensitivity for
      letter identification vs. frequency of the band-pass filters exhibit spatial
      tuning. In general, the spatial-frequency characteristics of letter
      identification are fundamentally identical between central and peripheral vision.
      These characteristics include the scaling of the peak frequency of the spatial
      tuning functions with letter size and the bandwidth of the tuning functions. The
      only difference between the fovea and the periphery is that for the same physical
      letter size, peak sensitivity of the spatial-tuning functions occurs at a higher
      retinal frequency at the fovea than in the periphery. To test whether or not the
      contrast sensitivity function (CSF) can account for the differences in the
      spatial-frequency characteristics of letter identification between central and
      peripheral vision, we incorporated a human CSF into an ideal-observer model, and
      tested the performance of this ideal-observer on the same letter identification
      task used with the human observers. Data from this CSF-ideal-observer resemble
      closely those of human observers, suggesting that the spatial-frequency
      characteristics of human letter identification can be accounted for by the CSF
      and the letter-identity information, without invoking selection among narrow-band
      spatial-frequency channels.

PMID- 12207976
TI  - Contour completion through depth interferes with stereoacuity.
AB  - Local disparity signals must interact in visual cortex to represent boundaries
      and surfaces of three-dimensional (3D) objects. We investigated how disparity
      signals interact in 3D contours and in 3D surfaces generated from the contours.
      We compared flat (single disparity) stimuli with curved (multi-disparity)
      stimuli. We found no consistent differences in sensitivity to contours vs.
      surfaces; for equivalent amounts of disparity, however, observers were more
      sensitive to flat stimuli than curved stimuli. Poor depth sensitivity for curved
      stimuli cannot be explained by the larger range of disparities present in the
      curved surface, nor by disparity averaging, nor by poor sensitivity to the
      largest disparity in the stimulus. Surprisingly, sensitivity to surfaces curved
      in depth was improved by removing portions of the surface and thus removing
      disparity information. Stimulus configuration had a profound effect on stereo
      thresholds that cannot be accounted for by disparity-energy models of V1
      processing. We suggest that higher-level 3D contour or 3D shape mechanisms are
      involved.

PMID- 12207977
TI  - Uniformity and asymmetry of rapid curved-line detection explained by parallel
      categorical coding of contour curvature.
AB  - The aim of this work was to elucidate several characteristic phenomena associated
      with rapid curved-line detection in multi-element arrays and to provide a unified
      account of the underlying curvature-sensitive mechanisms. To this end, a
      parametric experiment was performed in which the detectability of a curved-line
      target in a briefly presented planar array of curved-line distractors was
      measured for a range of target and distractor curvatures and distractor numbers.
      For both vertically oriented and randomly oriented curved lines, it was found
      that (1) the dependence of target detectability on target curvature was
      independent of distractor number for small distractor curvatures but not for
      medium-to-large distractor curvatures; (2) an asymmetry in target detectability
      with respect to interchange of target and distractor curvatures occurred only
      with large distractor numbers; and (3) with small distractor numbers, target
      detectability depended only on the difference between target and distractor
      curvatures. These properties of spatial parallelism, asymmetry, and uniformity
      were explained quantitatively by a minimal model of rapid curved-line detection
      in which contour curvature was coded in terms of just two or three curvature
      categories, depending on curved-line orientation.

PMID- 12207978
TI  - Recognizing spatial patterns: a noisy exemplar approach.
AB  - Models of categorization typically rely on the use of stimuli composed of well
      defined dimensions (e.g., Ashby & Maddox (1998) in Choice, decision, and
      measurement: Essays in honor of R. Duncan Luce, p. 251-301, Mahwah, NJ: Erlbaum).
      We apply a similar approach to the analysis of recognition memory. Using a
      version of short-term recognition paradigm (Sternberg, Science 153 (1966) 652),
      we asked whether NEMO Sternberg's, a noisy exemplar summed-similarity model,
      could account for variation in mean performance on individual trials. NEMO
      provided a very good overall fit to recognition data from three experiments.
      However, its failure to fit data for certain lists of stimuli suggested a
      revision of the summed-similarity assumption. Our model-based analysis showed
      that subjects used interitem similarity, in addition to probe-item similarity, as
      the basis for their decisions. This represents a major departure from existing
      recognition models that assume subjects' judgments depend exclusively on the
      summed similarity of the probe to the study items.

PMID- 12207979
TI  - Perceptual learning of highly demanding visual search tasks.
AB  - Inefficient visual search can become efficient with practice [Vision Research 35
      (1995) 2037; 40 (2000) 2925]. In this study, we wondered whether this improvement
      depends on unique visual features associated with the target, on differences in
      item-specific brightness distribution between target and distractors, or only on
      a change in the allocation of attention and thus global search strategy. We found
      that both, unique visual features and differences in brightness distribution lead
      to parallelisation with practice of originally inefficient search. Prolonged
      practice of inefficient search tasks lacking both unique visual features and
      differences in brightness distribution (conjunctions) does not lead to improved
      performance, thus indicating that perceptual learning in visual search does not
      solely reflect an unspecific global improvement in search strategy. Changing the
      brightness polarity of the stimuli leads to instantaneous, complete transfer to
      the new task. There is no transfer but rather trade-off between the learning
      based on unique visual features or on differences in brightness distribution
      between target and distractors.

PMID- 12207980
TI  - The vestibulo-ocular reflex in fourth nerve palsy: deficits and adaptation.
AB  - The effects of fourth nerve palsy on the vestibulo-ocular reflex (VOR) had not
      been systematically investigated. We used the magnetic scleral search coil
      technique to study the VOR in patients with unilateral fourth nerve palsy during
      sinusoidal head rotations in yaw, pitch and roll at different frequencies. In
      darkness, VOR gains are reduced during incyclotorsion, depression and abduction
      of the paretic eye, as anticipated from paresis of the superior oblique muscle.
      VOR gains during excyclotorsion, elevation and adduction of the paretic eye are
      also reduced, whereas gains in the non-paretic eye remain normal, indicating a
      selective adjustment of innervation to the paretic eye. In light, torsional
      visually enhanced VOR (VVOR) gains in the paretic eye remain reduced; however,
      visual input increases vertical and horizontal VVOR gains to normal in the
      paretic eye, without a conjugate increase in VVOR gains in the non-paretic eye,
      providing further evidence of selective adaptation in the paretic eye. Motions of
      the eyes after fourth nerve palsy exemplify monocular adaptation of the VOR, in
      response to peripheral neuromuscular deficits.

PMID- 12207981
TI  - Mr. Chips 2002: new insights from an ideal-observer model of reading.
AB  - The integration of visual, lexical, and oculomotor information is a critical part
      of reading. Mr. Chips is an ideal-observer model that combines these sources of
      information optimally to read simple texts in the minimum number of saccades.
      This model provides a computational framework for interpreting human reading
      saccades in both normal and low vision. The purpose of this paper is to report
      performance of the model for conditions emulating reading with normal vision--a
      visual span of nine characters, multiplicative saccade noise with a standard
      deviation of 30%, and texts based on three full-length children's books.
      Comparison of fixation locations by humans and Mr. Chips revealed: (1) that both
      exhibit very similar word-skipping behavior; (2) both show initial fixations near
      the center of words, but with a systematic difference suggestive of an asymmetry
      in the human visual span; and (3) differences in the pattern of refixations
      within words that may uncover non-optimal lexical inference by human readers. A
      human context effect--30% difference in mean saccade size between continuous text
      and random sequences of words--was very similar to the 25% effect for the model
      associated with a corresponding difference in the predictability of text words.
      Overall, our findings show that many of the complicated aspects of human reading
      saccades can be explained concisely by early information-processing constraints.

PMID- 12207982
TI  - Numerical modelling of the accommodating lens.
AB  - Data on geometric and material properties of the human lens derived from various
      published sources are used to construct axisymmetric, large displacement, finite
      element models of the accommodating lens of subjects aged 11, 29 and 45 years.
      The nucleus, cortex, capsule and zonule are modelled as linearly elastic
      materials. The numerical model of the 45-year lens is found to be significantly
      less effective in accommodating than the 29-year lens, suggesting that the
      modelling procedure is capable of capturing at least some of the features of
      presbyopia. The model of the 11-year lens shows some anomalous behaviour, and
      reasons for this are explored.

PMID- 12207983
TI  - Visual search in Alzheimer's disease: a deficiency in processing conjunctions of
      features.
AB  - Human vision often needs to encode multiple characteristics of many elements of
      the visual field, for example their lightness and orientation. The paradigm of
      visual search allows a quantitative assessment of the function of the underlying
      mechanisms. It measures the ability to detect a target element among a set of
      distractor elements. We asked whether Alzheimer's disease (AD) patients are
      particularly affected in one type of search, where the target is defined by a
      conjunction of features (orientation and lightness) and where performance depends
      on some shifting of attention. Two non-conjunction control conditions were
      employed. The first was a pre-attentive, single-feature, "pop-out" task,
      detecting a vertical target among horizontal distractors. The second was a single
      feature, partly attentive task in which the target element was slightly larger
      than the distractors-a "size" task. This was chosen to have a similar level of
      attentional load as the conjunction task (for the control group), but lacked the
      conjunction of two features. In an experiment, 15 AD patients were compared to
      age-matched controls. The results suggested that AD patients have a particular
      impairment in the conjunction task but not in the single-feature size or pre
      attentive tasks. This may imply that AD particularly affects those mechanisms
      which compare across more than one feature type, and spares the other systems and
      is not therefore simply an 'attention-related' impairment. Additionally, these
      findings show a double dissociation with previous data on visual search in
      Parkinson's disease (PD), suggesting a different effect of these diseases on the
      visual pathway.

PMID- 12207984
TI  - Progressive impairment of constructional abilities: a visuospatial sketchpad
      deficit?
AB  - The case of a patient, PC, with an impairment of constructional abilities due to
      a progressive degenerative disease is described. Ideomotor apraxia was also
      present. PC showed difficulties in all tasks requiring a "manipulation" of a
      visual model or requiring a visual model to address a specific movement or a
      choice among alternatives. The spatial component of mental imagery was also
      severely impaired. The conclusion was that the patient presented a deficit of the
      rehearsal component of the visuospatial sketchpad (VSSP). This produced an
      impairment of spatial learning, but spatial retrograde memory was preserved, as
      well as object recognition. The most prominent sites of atrophy were located in
      the parietal lobe bilaterally. A 3-year follow-up is reported, showing a
      progressive impairment of verbal abilities.

PMID- 12207985
TI  - Vertical sound localization in blind humans.
AB  - It is widely held that early-blind people compensate their visual loss by a
      general sharpening of spatial hearing. The present study reports a possible
      exception to this view: when the vertical position (elevation) of a sound source
      had to be localized, four out of six early-blind subjects exhibited systematic
      deviations in pointing, while two early-blind subjects were as accurate as
      sighted controls. On the other hand, blind and sighted individuals were able to
      judge relative positions of different sound locations with similar precision.
      These results suggest that visual experience may be used to accurately calibrate
      the relation between the vertical coordinates of auditory space and body, but is
      not needed to develop sufficiently high resolution of spatial hearing.

PMID- 12207986
TI  - The role of the vertical meridian in visual memory for objects.
AB  - It is widely believed that, in human and nonhuman primates, visual memories of
      objects are stored in the temporal lobe. Electrophysiological results in monkeys,
      however, indicate that when a visual scene contains two or more objects, with at
      least one object in each visual hemifield, neurons in the temporal lobe of each
      hemisphere respond only to the objects that are in the contralateral visual
      hemifield, and their activity is unaffected by the objects in the ipsilateral
      hemifield. Putting these two premises together predicts that object memory should
      fail, or at least suffer a substantial decrement, when an object is presented for
      learning and retention as part of such a scene, but crosses the vertical meridian
      between the learning trial and the retention test. The effect of this change
      should be much greater than the effect of an equal retinal translation that
      crosses the horizontal rather than the vertical meridian. An experiment with
      normal human subjects verified this prediction under conventional conditions of
      tachistoscopic viewing, with a single constant fixation spot. A further condition
      in the same experiment, however, tested the same retinal translations in a more
      naturalistic condition, where the retinal changes were produced by varying the
      position on the display screen of the fixation spot rather than of the objects.
      Here, there was no significant special effect of crossing the vertical meridian.
      We conclude that visual memories are not stored exclusively in the temporal lobe.

PMID- 12207987
TI  - Evidence for magnocellular involvement in the identification of flanked letters.
AB  - Little is known about the role of the magno system in reading. One important
      hypothesis is that this system is involved in the allocation of attention. We
      reasoned that the presentation of a single letter automatically draws attention
      to this letter, whereas in the case of a flanked letter, an additional process of
      attention allocation is required for identification to occur. In three letter
      naming experiments with 24 subjects each, normally reading adults were presented
      with flanked (e.g. xax) and with single (e.g. a) letters at three possible
      (para)foveal locations. The letters appeared in magno-disadvantageous colour
      contrast or in parvo-disadvantageous weak luminance contrast with the background.
      A control experiment verified that colour contrast had generated less
      magnocellular activity than had luminance contrast. Colour-contrast presentation
      led to a significantly lower naming performance for flanked letters than did
      luminance-contrast presentation, despite the fact that the two contrasts did not
      elicit differences in naming performance when the letters were presented in
      isolation. This latter finding rules out the possibility that colour contrast had
      generated not only less magno- but also less parvocellular activity than had
      luminance contrast. Thus, it can be concluded that the magno system is involved
      in the identification of flanked letters. This conclusion supports the hypothesis
      that the magno system is important to the allocation of attention. Further, it
      may provide an explanation for the frequent finding that people with
      developmental dyslexia have impairments in their magnocellular system.

PMID- 12207988
TI  - Orbitofrontal cortex mediates inhibition of return.
AB  - Recent accounts have proposed that orbitofrontal cerebral cortex mediates the
      control of behavior based on emotional feedback and its somatic correlates. Here,
      we describe the performance of a patient with circumscribed damage to
      orbitofrontal cortex during a task that requires switching between sensory-motor
      mappings, contingent on the occurrence of positive and negative reward feedbacks.
      In this test, normal subjects and other patients with prefrontal damage show an
      increase in latencies for eye movements towards locations at which a negative
      feedback was presented on the preceding trial. In contrast, our patient does not
      show this reward-dependent inhibition of return effect on saccades. She was also
      found to make an increased rate of ocular refixations during visual search and
      used a disorganized search strategy in a token foraging task. These findings
      suggest that orbital regions of the prefrontal cortex mediate an inhibitory
      effect on actions directed towards locations that have been subject to negative
      reinforcement. Further, this mechanism seems to play a role in controlling
      natural search and foraging behavior.

PMID- 12207989
TI  - Hemispheric lateralization of the processing of consonant-vowel syllables
      (formant transitions): effects of stimulus characteristics and attentional
      demands on evoked magnetic fields.
AB  - It is still unsettled in how far temporal resolution of dynamic acoustic events
      (formant transitions) or phonetic/linguistic processes contribute to predominant
      left-hemisphere encoding of consonant-vowel syllables. To further elucidate the
      underlying mechanisms, evoked magnetic fields in response to consonant-vowel
      events (synthetic versus spoken) were recorded (oddball design:
      standards=binaural/ba/, deviants=dichotic/ba/-/da/; 20 right-handed subjects)
      under different attentional conditions (visual distraction versus stimulus
      identification). Spoken events yielded a left-lateralized peak phase of the
      mismatch field (MMF; 150-200ms post-stimulus onset) in response to right-ear
      deviants during distraction. By contrast, pre-attentive processing of synthetic
      items gave rise to a left-enhanced MMF onset (100ms), but failed to elicit later
      lateralization effects. In case of directed attention, synthetic deviants
      elicited a left-pronounced MMF peak resembling the pre-attentive response to
      natural syllables. These interactions of MMF asymmetry with signal structure and
      attentional load indicate two distinct successive left-lateralization effects:
      signal-related operations and representation of 'phonetic traces'. Furthermore, a
      right-lateralized early MMF component (100ms) emerged in response to natural
      syllables during pre-attentive processing and to synthetic stimuli in case of
      directed attention. Conceivably, these effects indicate right hemisphere
      operations prior to phonetic evaluation such as periodicity representation. Two
      distinct time windows showed correlations between dichotic listening performance
      and ear effects on magnetic responses reflecting early gain factors (ca. 75ms
      post-stimulus onset) and binaural fusion strategies (ca. 200ms), respectively.
      Finally, gender interacted with MMF lateralization, indicating different
      processing strategies in case of artificial speech signals.

PMID- 12207990
TI  - Unilateral neglect and perceptual parsing: a large-group study.
AB  - Array-centred and subarray-centred neglect were disambiguated in a group of 116
      patients with left neglect by means of a modified version of the Albert test in
      which the central column of segments was deleted so as to create two separate
      sets of targets grouped by proximity. The results indicated that neglect was more
      frequent in array- than subarray-centred coordinates and that, in a minority of
      cases, neglect co-occurred in both coordinate-systems. The two types of neglect
      were functionally but not anatomically dissociated. Presence of visual field
      defects was not prevalent in one type of neglect with respect to the other. These
      data contribute further evidence to previous single-case and small-group studies
      by showing that neglect can occur in single or multiple reference frames
      simultaneously, in agreement with current neuropsychological, neurophysiological
      and computational concepts of space representation.

PMID- 12207991
TI  - Mechanisms underlying perseveration in aphasia: evidence from a single case
      study.
AB  - Aphasic individuals often inappropriately and unintentionally repeat recent
      responses, errors termed recurrent perseverations. In a series of picture naming
      experiments, we investigated the impact of manipulating stimulus factors on the
      number of perseverations produced by an aphasic patient (E.B.) with markedly
      impaired naming skills. E.B. produced significantly more perseverations to
      pictures with low frequency names and following stimulus repetition. In contrast,
      semantic relatedness and presentation rate failed to influence perseveration. Our
      results are considered in the context of theories that relate recurrent
      perseverations to intact priming mechanisms [Brain 121 (1998) 1641; Aphasiology
      12 (1998) 319; J. Exp. Psychol. Learn. Mem. Cogn. 19 (1993) 243]. We conclude
      that these theories can correctly predict some but not all aspects of E.B.'s
      perseverations. In particular, they failed to predict that: (1) perseverations
      often appeared to reflect the earlier sequential proximity of stimuli and
      responses; and (2) perseverations became less likely as more experimental trials
      intervened, a trend that did not interact with presentation rate. We review
      evidence relating recurrent perseverations to neuromodulatory deficits and we
      conclude that a theory of the functional role of neuromodulation in the cerebral
      cortex proposed by Hasselmo [Neural Netw. 7 (1994) 13] is capable of accounting
      for all aspects of E.B.'s perseverative behavior.

PMID- 12207992
TI  - Task switching deficits associated with Parkinson's disease reflect depleted
      attentional resources.
AB  - Using a Stroop task switching paradigm, Brown and Marsden [Brain 111 (1988) 323;
      Brain 114 (1991) 215] proposed that set shifting deficits in Parkinson's disease
      (PD) reflect limited attentional resources rather than deficits in internal
      control, as was previously supposed. In the present study, we tested this claim
      using a more recently developed Stroop task switching paradigm for which the
      internal control and attentional resources accounts made contrasting predictions.
      A PD group (N=30) was compared with an age-matched control group (N=34) on vocal
      response time (RT) for color naming and word reading in response to neutral and
      incongruent Stroop stimuli. Participants carried out four blocks of task
      repetition trials, and eight blocks of task switching trials. The results
      revealed that a deficit due to PD was absent for two conditions necessitating
      internal control, but was present in the condition which placed the highest
      demand on attentional resources. This selective deficit is congruent with Brown
      and Marsden's conclusions that depleted attentional resources, not an impairment
      in internal control per se, is the basis of the set shifting deficits associated
      with PD.

PMID- 12207993
TI  - The neuroanatomical substrate of sound duration discrimination.
AB  - We investigated the neuroanatomical substrate of sound duration discrimination,
      using the same experimental design as in a previous study on sound intensity
      discrimination [J. Neurosci. 18 (16) (1998) 6388]. Seven normal subjects were
      trained to detect deviant sounds presented with a slightly longer duration than a
      300 ms long standard harmonic sound, using a Go/No Go paradigm. Individual
      psychometric curves were assessed using a three-step psychoacoustic procedure.
      Subjects were then scanned while passively listening to the standard sound, and
      while discriminating changes in sound duration at four different performance
      levels (d'=1.5, 2.5, 3.5 and 4.5). Analysis of regional cerebral blood flow
      (rCBF) data outlined activation, during the discrimination conditions, of a right
      hemispheric fronto-parietal network very similar to the one previously observed
      for intensity discrimination, as well as additional activation in the right
      prefrontal cortex (Brodmann Area (BA) 10), bilateral basal ganglia and cerebellar
      hemispheres. These findings suggest that discrimination of sound duration, as for
      discrimination of sound intensity, involves two cerebral networks: a supramodal
      right fronto-parietal cortical network responsible for allocation of sensory
      attentional resources, and a network of regions such as the basal ganglia,
      cerebellum, and right prefrontal cortex, more specifically involved in the
      temporal aspects of the discrimination task.

PMID- 12207994
TI  - Visual, proprioceptive and tactile performance in left neglect patients.
AB  - Patients with unilateral spatial neglect due to right-hemisphere lesions
      typically fail to attend to and explore left-sided stimulus objects. It has been
      postulated that in right-brain damaged (RBD) patients an ipsilesional
      displacement of the egocentric frame of reference (ER), whether visual or
      tactile, may be responsible for a contralesional supramodal spatial bias causing
      their left neglect behavior. However, this hypothesis had been proposed without
      testing, in the same patients, the position of the ER or their performance in the
      visual and tactile modalities. Thus, the aim of the present study was to test the
      hypothesis that an ipsilateral shift of the ER is responsible for a supramodal
      spatial bias in neglect. For this purpose, a within-subject design is required.
      Consequently, 12 left neglect patients and 12 control subjects were asked to
      perform a proprioceptive straight-ahead pointing task while blindfolded, as well
      as visual and tactile bisection tasks. In the left neglect patients, we found:no
      systematic deviation of the ER on the ipsilesional right side;a significant
      rightward bias in visual bisection, and normal performance in tactile
      bisection;no correlation among the three tasks;that only visual bisection
      correlated with the severity of neglect. These results are discussed with regard
      to the egocentric and attentional hypothesis of neglect.

PMID- 12207995
TI  - Impaired perception of temporal order in auditory extinction.
AB  - It has been proposed that patients with extinction show a chronic bias of spatial
      attention towards the ipsilesional side. In this case, the law of 'prior entry'
      predicts that ipsilesional events should be perceived earlier than physically
      synchronous contralesional stimuli. In line with this prediction, previous
      studies have revealed substantial delays of awareness for contralesional visual
      and tactile events in patients with visual and with tactile extinction. The
      present study provides evidence that a 'prior entry' bias also occurs in the
      auditory modality. Patients with auditory extinction perceived two acoustic
      events (one presented to the left ear, the other to the right ear) as being
      'simultaneous' when the contralesional sound was leading by 270 ms. The magnitude
      of this asynchrony was quite similar to that measured previously in the visual
      modality. Thus, the pathological delay of awareness for contralesional events may
      be independent of the sensory modality of the stimuli.

PMID- 12207996
TI  - Interhemispheric communication of abstract and specific visual-form information.
AB  - Pairs of letters were compared after being viewed in different visual fields
      (i.e. across-hemispheres, AH) or in the same visual field (i.e. within
      hemisphere, WH). In an abstract-category comparison task, participants decided
      whether two letter exemplars belonged to the same abstract category (e.g. "k" and
      "K") or not (e.g. "k" and "P") and performed more accurately in AH trials than in
      WH trials. In a specific-exemplar comparison task, they decided whether two
      letters within the same abstract category were the same specific exemplars (e.g.
      "k" and "k") or not (e.g. "k" and "K") and performed more accurately in WH trials
      than in AH trials. This pattern of results was observed when the exemplars in a
      category were visually similar (e.g. "k" and "K", "a" and "a") but not when they
      were visually dissimilar (e.g. "a" and "A"). The reversed association technique
      was used to confirm the independence of subsystems underlying abstract category
      and specific-exemplar comparisons. Most important, the results support the theory
      that a specific-exemplar subsystem is more detrimentally affected by
      interhemispheric transfer of information than an abstract category subsystem.

PMID- 12207997
TI  - Spatial shifts in visual attention in normal ageing and dementia of the Alzheimer
      type.
AB  - Using a spatial-cueing paradigm, we assessed the ability of Alzheimer's disease
      patients, age-matched controls and younger participants to use cues to guide
      attention to the location indicated by the cue. In separate experiments, we
      attempted to isolate cues that attract attention automatically (exogenous cueing)
      and those that require the wilful movement of attention (endogenous cues). We
      found significant cueing effects for all three groups of participants for both
      types of cue. However, the group with Alzheimer's disease showed far greater
      cueing effects when using an exogenous cue, whilst no difference between group's
      ability to use the cue was found for the endogenous cue. No differences in cueing
      were found for either cue type as a function of normal ageing. We further tested
      whether the differences in cueing found in the group with Alzheimer's disease was
      due to a generalised slowing of function. After transforming the data to take
      account of the overall slowing of all responses in this group, we still found
      significant differences between this group and the control groups. We conclude
      that patients with Alzheimer's disease have an abnormality in automatic, but not
      controlled visuospatial attention.

PMID- 12207998
TI  - Risky decisions and response reversal: is there evidence of orbitofrontal cortex
      dysfunction in psychopathic individuals?
AB  - This study investigates the performance of psychopathic individuals on tasks
      believed to be sensitive to dorsolateral prefrontal and orbitofrontal cortex
      (OFC) functioning. Psychopathic and non-psychopathic individuals, as defined by
      the Hare psychopathy checklist revised (PCL-R) [Hare, The Hare psychopathy
      checklist revised, Toronto, Ontario: Multi-Health Systems, 1991] completed a
      gambling task [Cognition 50 (1994) 7] and the intradimensional/extradimensional
      (ID/ED) shift task [Nature 380 (1996) 69]. On the gambling task, psychopathic
      participants showed a global tendency to choose disadvantageously. Specifically,
      they showed an impaired ability to show learning over the course of the task. On
      the ID/ED task, the performance of psychopathic individuals was not significantly
      different from incarcerated controls on attentional set-shifting, but significant
      impairments were found on response reversal. These results are interpreted with
      reference to an OFC and amygdala dysfunction explanation of psychopathy.

PMID- 12207999
TI  - Dopamine and the representation of the upper visual field: evidence from vertical
      bisection errors in unilateral Parkinson's disease.
AB  - It has been suggested that dopamine is an important neurotransmitter in the brain
      mechanisms which represent the upper visual field. This idea was tested with a
      vertical line bisection task in unilateral Parkinson's disease. Stimuli of a
      range of lengths were presented on a large screen in three positions (left,
      centre and right) and at two viewing distances (0.6 and 1.5m). The patients, who
      were compared with a group of normal age-matched controls, comprised 16 sufferers
      from predominantly unilateral disease, 8 with more severe left-sided symptoms
      (LPD) and 8 with more severe right-sided symptoms (RPD). The LPD group
      consistently set the bisecting cursor below the midpoint of the stimulus lines,
      and their bisection error became larger as the length of the line increased. In
      contrast, the controls set the cursor above the midpoint of the line, an error
      which also increased with line length. The settings of the RPD group were similar
      to those of the controls. The results suggest altitudinal neglect in left
      unilateral PD, and support the hypothesis of dopaminergic involvement in the
      coding of upper visual space, with the proviso that the perceptual component of
      this involves the right hemisphere in humans.

PMID- 12208000
TI  - Chronic anosognosia: a case report and theoretical account.
AB  - Unawareness of motor disorders (anosognosia) has often been reported after brain
      lesions, and it has been considered a temporary condition common in the acute and
      post-acute phases. The presence of anosognosia in a chronic phase (i.e. lasting
      more than few weeks) is a rare occurrence, thought to be the result of reasoning
      deficits which prevent patients from performing an adequate check of reality.
      Although this assumption is widely shared amongst researchers, only a few studies
      have actually addressed this issue. We report on the case of a patient (NS) who
      was still showing anosognosia for hemiplegia 1 year after a traumatic brain-head
      injury, while his reasoning abilities were well preserved. By means of a series
      of tests and experiments, we evaluated the main theoretical approaches. NS's long
      lasting anosognosia is discussed in terms of a combination of clinical
      manifestations, whereby personal neglect and motor-sensory information play a key
      role in preventing awareness, whereas memory difficulties in updating pre
      existing personal schema may be crucial in maintaining NS's anosognosic status.

PMID- 12208001
TI  - Deficits in the initiation of eye movements in the absence of a visual target in
      adolescents with high functioning autism.
AB  - BACKGROUND: We used ocular motor paradigms to examine whether or not saccades are
      impaired in individuals with high functioning autism (HFA). METHODS: We recorded
      eye movements in patients with HFA (n=11), and in normal adolescents (n=11) on
      anti-saccade, memory-guided saccade (MGS), predictive saccade and gap/overlap
      tasks. RESULTS: Compared with the normal subjects, patients with HFA had (1) a
      significantly higher percentage of directional errors on the anti-saccade task
      (63.2% versus 26.6%), (2) a significantly higher percentage of response
      suppression errors on a MGS task (60.3% versus 29.5%) and (3) a significantly
      lower percentage of predictive eye movements on a predictive saccade task. They
      also showed longer latencies on a MGS task and for all conditions tested on a
      gap/null/overlap task (fixation target extinguished before, simultaneously, or
      after the new peripheral target appeared). When the latencies during the gap
      condition were subtracted from the latencies in the overlap condition, there was
      no difference between patients and normals. CONCLUSIONS: Abnormalities in ocular
      motor function in patients with HFA provide preliminary evidence for involvement
      of a number of brain regions in HFA including the dorsolateral prefrontal cortex
      (dlPFC) and the frontal eye fields (FEFs) and possibly the basal ganglia and
      parietal lobes.

PMID- 12208002
TI  - Age-related dedifferentiation of visuospatial abilities.
AB  - Forty-eight older adults were tested on a battery of seven speeded visuospatial
      tasks that were developed by Chen et al. to measure the functions of the ventral
      and dorsal neural processing streams. Principal components analysis revealed only
      one factor with an eigenvalue greater than 1.0, and all of the tasks loaded
      heavily on this general factor. These results are in contrast to those reported
      in a previous study of young adults in which principal components analysis
      revealed two factors with eigenvalues greater than 1.0. Importantly, for young
      adults the second principal component was a bipolar factor which grouped the
      tasks based on the neural processing stream (i.e. ventral versus dorsal) whose
      function they had been designed to assess. The age-related difference in the
      factor structure of visuospatial abilities apparent from the present results may
      be interpreted as reflecting an age-related dedifferentiation of the neural
      processing streams consistent with the results of recent neuroimaging studies.

PMID- 12208003
TI  - Human brain potential correlates of repetition priming in face and name
      recognition.
AB  - We investigated repetition priming in the recognition of famous people by
      recording event-related brain potentials (ERPs) and reaction times (RTs).
      Participants performed speeded two-choice responses depending on whether or not a
      stimulus showed a famous person. In Experiment 1, a facilitation was found in RTs
      to famous (but not to unfamiliar) faces when primed by the same face shown in an
      earlier priming phase of the experiment. In ERPs, an influence of repetition
      priming was observed neither for the N170 nor for a temporal N250 component which
      in previous studies had been shown to be sensitive to immediate face repetitions.
      ERPs to primed unfamiliar faces were more negative over right occipitotemporal
      areas than those to unprimed faces, but this effect was specific for repetitions
      of the same image, consistent with recent findings. In contrast, ERPs to primed
      familiar faces were more positive than those to unprimed faces at parietal sites
      from 500-600 ms after face onset, and these priming effects were comparable
      regardless of whether the same or a different image of the celebrity had served
      as prime. In Experiment 2, similar results were found for name recognition-a
      facilitation in RTs to primed familiar but not unfamiliar names, and a parietal
      positivity to primed names around 500-600 ms. ERP repetition effects showed
      comparable topographies for faces and names, consistent with the idea of a common
      underlying source. With reference to current models of face recognition, we
      suggest that these ERP repetition effects for familiar stimuli reflect a change
      in post-perceptual representations for people, rather than a neural correlate of
      recognition at a perceptual level.

PMID- 12208004
TI  - The effects of hand preference side and hand preference switch history on
      measures of psychological and physical well-being and cognitive performance in a
      sample of older adult right-and left-handers.
AB  - Claims have been made that left-handedness often arises from pathological causes,
      and that owing to this underlying pathology, the presence of sinistrality may
      entail disadvantages for both the length and quality of life. A prime implication
      of these claims is that left-handers, as a group, should display signs of poorer
      fitness than right-handers. This poorer fitness might take the form of an
      increased incidence of illnesses and/or accidents. In addition, it might also be
      predicted that left-handers would experience a psychological and, perhaps,
      cognitive quality of life that is inferior to that of right-handers. In the
      present study, we measured a large sample (N=1277) of older adults on four
      indexes of lateral preference (hand, foot, eye, and ear), on whether or not they
      experienced pressure to switch their preferred writing hand, and variables
      related to psychological well-being, physical health, and cognitive performance.
      The results revealed that the presence of left hand writing, in isolation, did
      not predict decreases in quality of life factors; however, in conjunction with
      left-handed writing, the presence of a hand preference switch report was shown to
      be important. In particular, one subset of left-handers-those who attempted to
      change their preferred writing hand but were unsuccessful-was found to have a
      lower quality of psychological and physical well-being on multiple measures.

PMID- 12208005
TI  - Vestibulo-ocular and optokinetic impairments in left unilateral neglect.
AB  - Right brain damaged patients affected by left unilateral neglect (N+) typically
      fail to explore the contralesional space. For the first time, this study
      investigates the dynamic and spatial features of the horizontal vestibular-ocular
      response (VOR), the optokinetic response (OKR) and the VOR-OKR interaction in six
      N+ and in five right brain damaged patients without neglect (N-). No lateral
      asymmetry of the gain (i.e. eye velocity to head velocity ratio) of VOR slow
      phases was found in either group. In the VOR, N+ had higher frequency of slow
      rightward/fast-leftward phases and higher contralesional shift of the beating
      field (i.e. orbital position of fast phases). In the VOR-OKR, there was an
      increase of gain in both lateral directions and in both groups even though in N-,
      there was a lower phase shift between eye and head velocity. In contrast to the
      VOR, in the VOR-OKR, N+ had higher frequency of slow-leftward/fast-rightward
      phases. The VOR-OKR interaction also introduced an ipsilesional shift of the
      beating field in both N+ and N-. In the OKR, N+ showed a drop in the velocity,
      amplitude and frequency of slow-rightward/fast-leftward phases. These findings
      potentially suggest that each hemisphere modulates VOR with contralaterally
      directed slow phases and OKR with ipsilaterally directed slow phases. This
      organisation could facilitate maintenance or fast recovery of combined VOR + OKR
      after unilateral brain damage. The same findings suggest that by inducing slow
      leftward phases, vestibular and optokinetic stimulation improve left side neglect
      through the activation of different hemispheric pathways. No ipsilesional
      deviation of the subjective "straight ahead" was found in N+. These results show
      that chronic unilateral neglect can be dissociated both from deficits of
      ipsilesionally directed VOR and from ipsilesional deviation of the subjective
      midsagittal plane of the body.

PMID- 12208006
TI  - Ipsilesional deficits during fast diadochokinetic hand movements following
      unilateral brain damage.
AB  - Impaired sensorimotor function of the hand ipsilateral to a unilateral brain
      lesion has been reported in a variety of motor tasks; however, elementary
      diadochokinetic movements, such as tapping with the index finger, seem to be
      preserved in chronic-lesion patients. Three different diadochokinetic movements
      (forearm diadochokinesis, hand tapping (HT) and finger tapping (FT)) were tested
      in patients with left brain damage (LBD) and right brain damage (RBD) and control
      subjects. Movements were measured three-dimensionally and the kinematics of joint
      angles were analyzed. While the patients' measures of movement speed and symmetry
      appeared normal, detailed kinematic analysis revealed clear deficits in several
      measures of movement variability, which reflected decreased regularity of the
      alternating movement cycles. This impairment was greater in LBD patients and
      tended to be greater during forearm diadochokinesis. The necessity of ipsilateral
      control in addition to dominant, contralateral control, especially during left
      hand and more complex or more proximal manual tasks may account for these
      findings. In addition, the role of apraxia (defined by impairments during the
      imitation of gestures) in the performance deficits of LBD patients was also
      assessed. Although, some performance decrements were associated with the presence
      of apraxia, these were different from the group findings and restricted to the
      two tapping tasks. Thus, although apraxia may have caused deficits in
      establishing dynamic representations of the elementary postures in conditions of
      high speed and low complexity, the disturbances during diadochokinetic movements
      must for the most part be attributed to more motor-related deficits of
      ipsilateral sensorimotor control, which are particularly apparent when the motor
      dominant left hemisphere is affected. The absence of clear correlations between
      performance deficits and lesion characteristics suggests that a distributed
      network is involved in this ipsilateral control.

PMID- 12208007
TI  - Spared error-related potentials in mild to moderate Parkinson's disease.
AB  - Several lines of evidence indicate that people with Parkinson's disease are
      impaired at detecting their own motor errors. In the present study, we use a
      component of the event-related brain potential called the error-related
      negativity (ERN) to ask whether a high-level, generic error-processing system is
      compromised in Parkinson's disease. We recorded the electroencephalogram (EEG)
      from nine patients with mild to moderate Parkinson's disease and from nine normal
      control subjects while they performed a choice reaction time task. We found that
      the amplitude of the ERN was the same for both populations, indicating that the
      error-processing system associated with the ERN is not severely compromised in
      this Parkinson's disease population. These results are discussed in terms of
      disease progression.

PMID- 12208008
TI  - Lateralized spatial processes and their lexical implications.
AB  - Numerous lateralized tasks have been identified as involving spatial processing,
      but the extent to which they use the same spatial process is largely unknown. The
      present research investigated relationships among significant asymmetries from
      seven visuo-spatial and two verbal tasks, combining samples from previous factor
      analytic experiments with those from three new studies (combined N=789). All of
      the spatial intercorrelations were negligible (r<0.20), unlike previous outcomes
      finding robust correlations within certain clusters of verbal asymmetries.
      However, lateral differences involving spatial quantitative processing on the one
      hand and figure-ground separation on the other, showed significant but
      independent correlations with one from visual lexical processing (word
      recognition). The results support three major conclusions. First, there are at
      least several and possibly many lateralized spatial processes. Second,
      hemispheric processes follow a modular architecture in preference to a diffuse or
      parallel distributed architecture. Finally, the dissociated correlations are
      consistent with a visual lexical processing model having both occipital and
      parietal components, potentially reconciling a current controversy over the
      cerebral localization of language.

PMID- 12208009
TI  - Evidence for cortical encoding specificity in episodic memory: memory-induced re
      activation of picture processing areas.
AB  - Functional magnetic resonance imaging (fMRI) was used to examine whether neural
      pathways used to encode pictures into memory were re-activated during retrieval
      of those memories. At encoding, subjects semantically classified common objects
      presented as pictures or words. At retrieval, subjects performed yes/no
      recognition memory judgments on words that had been encoded as pictures or as
      words. The retrieval test probed memory for the encoded item, but not memory for
      the modality of the encoded item (picture/word). Results revealed that a subset
      of the brain regions involved specifically in encoding of pictures were also
      engaged during recognition memory for the encoded pictures. Specifically,
      encoding of pictures relative to words engaged bilateral extrastriate visual
      cortex, namely fusiform, lingual, middle occipital, and inferior temporal gyri
      (Broadman area (BA) 18/19/37). Recognition memory judgments about words that were
      encoded as pictures relative to those that were encoded as words activated
      fusiform and inferior temporal gyri primarily in the left hemisphere. Thus,
      cortical areas originally involved in perception of a visual experience become
      part of the long-term memory trace for that experience. These findings suggest a
      neural basis for encoding specificity and transfer appropriate processing in
      human memory.

PMID- 12208010
TI  - Executive functioning in adults and children with developmental dyslexia.
AB  - The performance of developmentally dyslexic children and adults was studied upon
      a range of tasks that involved executive functioning. Both adult and child
      samples of dyslexics were found to under-perform on the group-embedded figures
      test. This test required the identification of constituent parts from within
      complex visual arrays, with good performance necessitating the inhibition of the
      processing of the surrounding context. A general deficit on visual-spatial tasks
      was eliminated as an explanation as dyslexics performed normally upon a range of
      other non-verbal assessments. The dyslexics consistently demonstrated a deficit
      in digit span tasks, a decrement that was increased with distractors, again
      suggesting difficulties in inhibiting the processing of the surrounding context.
      A deficit was also identified upon a verbal fluency task without a deficit in
      vocabulary level. Additionally, a specific deficit in the recollection of the
      temporal order of the presentation of items was in evidence, without a deficit in
      the recognition of the items themselves. The findings taken as a whole suggest
      that dyslexic individuals show deficiencies in executive functions relating to
      inhibition of distractors and to sequencing of events, a set of tasks associated
      with left prefrontal cortex functioning in the acquired neuropsychology
      literature.

PMID- 12208011
TI  - Neural response to emotional faces with and without awareness: event-related fMRI
      in a parietal patient with visual extinction and spatial neglect.
AB  - This study examined whether differential neural responses are evoked by emotional
      stimuli with and without conscious perception, in a patient with visual neglect
      and extinction. Stimuli were briefly shown in either right, left, or both fields
      during event-related fMRI. On bilateral trials, either a fearful or neutral left
      face appeared with a right house, and it could either be extinguished from
      awareness or perceived. Seen faces in left visual field (LVF) activated primary
      visual cortex in the damaged right-hemisphere and bilateral fusiform gyri.
      Extinguished left faces increased activity in striate and extrastriate cortex,
      compared with right houses only. Critically, fearful faces activated the left
      amygdala and extrastriate cortex both when seen and when extinguished; as well as
      bilateral orbitofrontal and intact right superior parietal areas. Comparison of
      perceived versus extinguished faces revealed no difference in amygdala for
      fearful faces. Conscious perception increased activity in fusiform, parietal and
      prefrontal areas of the left-hemisphere, irrespective of emotional expression;
      while a differential emotional response to fearful faces occurring specifically
      with awareness was found in bilateral parietal, temporal, and frontal areas.
      These results demonstrate that amygdala and orbitofrontal cortex can be activated
      by emotional stimuli even without awareness after parietal damage; and that
      substantial unconscious residual processing can occur within spared brain areas
      well beyond visual cortex, despite neglect and extinction.

PMID- 12208012
TI  - When writing 0 (zero) is easier than writing O (o): a neuropsychological case
      study of agraphia.
AB  - Though a few case studies reported a dissociation between intact writing of
      Arabic and impaired writing of alphabetical script, a detailed experimental
      analysis of such a dissociation is still lacking. We report a follow-up study of
      a patient with a parieto-occipital lesion who is affected by severe peripheral
      agraphia for letters, but not for Arabic digits. While letters in writing to
      dictation are frequently illegible, distorted, or consist in meaningless strokes,
      Arabic digits are well-formed and fluently produced. In a series of tasks,
      including copying of letters with tachistoscopic presentation and handwriting on
      a digitizing tablet, several processing levels are assessed in order to localize
      JS' functional writing impairment and to determine different processing routes
      for letters and for numbers. Overall, the results of the experimental
      investigation suggest a notation specific deficit in the activation of
      graphomotor patterns for letters, but not for digits. The study thus adds
      evidence to the so far reported dissociations between Arabic and alphabetical
      scripts.

PMID- 12208013
TI  - Cognitive dysfunction in adult males with non-syndromic clefts of the lip and/or
      palate.
AB  - Cognitive deficits have been well-documented in children with non-syndromic
      clefts of the lip and/or palate. However, no study to date has formally assessed
      cognition in adults with oral clefts. This study was designed to evaluate
      neuropsychological functioning in adult males with non-syndromic clefts of the
      lip and/or palate (n=50) compared to age and sex-matched controls. Subjects with
      oral clefts were found to have significantly lower full scale IQ, performance IQ
      and verbal IQ scores compared to their matched controls. After controlling for
      IQ, patients showed specific deficits in verbal fluency. Adult males with oral
      clefts manifest a specific pattern of cognitive deficits. As the development of
      the face is highly interdependent with the development of the brain, it is
      theorized that the etiology of these cognitive deficits is a primary problem with
      abnormal brain development.

PMID- 12208015
TI  - Proceedings of TIAFT2001PRAGUE. The 39th Meeting of the International Association
      of Forensic Toxicologists (TIAFT). Prague, Czech Republic. August 27-30, 2001.

PMID- 12208014
TI  - Is implicit learning spared in amnesia? Rule abstraction and item familiarity in
      artificial grammar learning.
AB  - We examined implicit learning of an artificial grammar in amnesic and control
      participants. The "biconditional" grammar used to generate study and test strings
      allows two potential sources of judgements in artificial grammar learning to be
      unconfounded: participants could either learn the abstract biconditional rules or
      could learn about the distributional statistics of the surface elements (e.g.
      bigrams) composing the study items. Test strings varied these two sources
      orthogonally. We found no evidence of abstract rule learning either in the
      control or amnesic groups. In contrast, both groups learned about the surface
      elements and tended to call test strings "grammatical" when they were composed of
      familiar bigrams. However, this sensitivity to bigram familiarity was
      significantly reduced in the amnesic compared to the control group. The results
      challenge the claim that implicit learning is intact in amnesia.

PMID- 12208016
TI  - Recording acute poisoning deaths.
AB  - Recording deaths from acute poisoning/substance abuse is not straightforward. The
      International Classification of Diseases (ICD), used to code mortality
      statistics, is aimed towards recording the underlying cause of death such as
      suicide or drug dependence rather than gathering data on poisoning per se.
      Despite the inherent difficulties clear trends can be observed from the data
      available for England and Wales. There have been marked changes in the compounds
      featuring in suicidal poisoning in the last 35 years reflecting changes in the
      availability of poisons, notably carbon monoxide and prescription barbiturates.
      However, although the number of poisoning suicides has decreased in the recent
      years, suicides from other means have increased in males (suicides in 1999, 75%
      male), hence there has been little change in the annual total of suicides. There
      are also striking differences in drug abuse- and volatile substance abuse (VSA)
      related deaths between males and females. Drug abuse-related fatal poisoning (83%
      male, 1979-1999, European Monitoring Centre for Drugs and Drug Addiction (EMCDDA)
      definition which does not include suicide), largely attributable to heroin and
      methadone, increased markedly during the 1990s, with a sharp rise in deaths
      attributed to accidental poisoning, although deaths involving methadone are now
      declining. VSA-related deaths (90% male, 1971-1999, almost entirely accidental
      deaths), nowadays predominantly from abuse of fuel gases (liquefied petroleum
      gas, LPG) from, for example, cigarette lighter refills, have declined from a peak
      in the early 1990s and are now becoming manifest in an older age group. These two
      latter instances especially provide examples where ICD-derived fatal poisoning
      data are inadequate and a 'poisons oriented' approach to data collection and
      analysis is necessary.

PMID- 12208017
TI  - Drug abuse's smallest victims: in utero drug exposure.
AB  - The social and economic impact of drug use on our global population continues to
      increase leaving no geographical, social or cultural group untouched. The
      National Institute on Drug Abuse (NIDA), in one of the few large surveys of
      maternal abuse, found that 5.5% of mothers reported taking an illicit substance
      during gestation. These figures certainly are underestimates due to the stigma of
      drug use during pregnancy and the accompanying legal, ethical and economic
      issues. Although drugs of choice and routes of administration vary by country,
      exposure of our most valuable resource, our children, to the developmental
      effects of drugs is an enormous problem. In utero drug exposure can have a severe
      impact not only on the development of the fetus, but also on the child during
      later stages of life. More than 75% of infants exposed to drugs have major
      medical problems as compared to 27% of unexposed infants. The cost of treating
      drug-affected infants was twice the cost of non-affected infants. Obstetrical
      complications including placental insufficiency, miscarriage, intrauterine death,
      and increased incidence of infectious and sexually-transmitted diseases are
      higher in the drug-abusing mother. Treatment for pregnant addicts should be a
      high priority for our governments. Increased awareness and improvement in our
      understanding of drug abuse in the medical, legal and social realms will enable
      us to reduce the barriers to treatment for this important population.Accurate
      identification of in utero drug exposure has important implications for the care
      of the mother and child, but can raise difficult legal issues. Society
      discourages prenatal care with the infliction of harsh criminal penalties.
      Maternal drug use during pregnancy can be monitored with urine, sweat, oral fluid
      and/or hair testing. Detection of in utero drug exposure has traditionally been
      accomplished through urine testing; however, the window of detection is short,
      reflecting drug use for only a few days before delivery. Monitoring exposure
      through testing of alternative matrices, such as neonatal meconium and hair,
      offers advantages including non-invasive collection and detection earlier in
      gestation. There are many unresolved issues in monitoring in utero drug exposure
      that urgently require research. These can be divided into research to
      definitively differentiate drug exposed and non-drug-exposed fetuses, determine
      the most efficient methods to routinely monitor women's drug use, and determine
      how these drug test results relate to neonatal and maternal outcomes. Research in
      this area is difficult and expensive to perform, but necessary to assess
      accurately drug effects on the fetus. By increasing our understanding of the
      physiological, biochemical and behavioral effects of gestational drug exposure,
      we may ultimately provide solutions for better drug prevention, treatment and a
      reduction in the number of drug-exposed children.

PMID- 12208018
TI  - Amphetamine derivative related deaths in northern Greece.
AB  - Until 1997, only one amphetamine related derivatives (AMPs) fatality had been
      reported in Greece. Since then, amphetamine (AMP) or AMPs have been found in
      seven out of 1,500 post-mortem toxicological cases. The cause and manner of death
      of these seven cases were: 3,4-methylenedioxy-N-methamphetamine (MDMA) and 3,4
      methylenedioxy-N-ethylamphetamine (MDEA) poisoning (n = 1), drowning in water (n
      = 4), cranial injuries caused by a traffic accident (n = 1) and heart failure (n
      = 1). In the case where the use of AMP or AMPs was considered, the immediate
      cause of death post-mortem toxicological analysis revealed 2 microg/ml MDMA and
      0.7 microg/ml MDEA in blood. MDMA was identified in two cases of drowning (2
      microg/ml in blood in the first case and 1.7 microg/g in liver in the second
      case) and in the traffic accident case (0.4 microg/g in liver). Methamphetamine
      was detected in two cases of drowning (2.5 microg/ml in blood in the first case
      and 6 microg/g in liver in the second case). AMP was found in the heart failure
      case (0.2 microg/g in liver). Alcohol was present, together with AMP or AMPs, in
      four cases. These findings indicate an increase in the illegal abuse of AMPs in
      Greece. Because of this, we now routinely screen for AMPs.

PMID- 12208019
TI  - Bile analysis of drugs in postmortem cases.
AB  - Bile is, in certain cases, collected together with blood from different sites
      (heart, brain, femoral), urine and other organs or matrices. This study reports
      comparative results obtained from the analysis of blood and bile for different
      drugs found: acetaminophen, amphetamine and related compounds, several
      antidepressants, several benzodiazepines, cocaine and its metabolites,
      dextropropoxyphene and its metabolite, hydroxyzine, methadone and metabolite,
      morphine and codeine, levomepromazine, thioridazine, propranolol, tramadol and
      its metabolite. Several findings are presented: (1) There were no significant
      differences in the levels of the compounds among the samples of blood obtained
      from different sites. (2) Levels in bile are generally several fold higher than
      those in blood. The mean bile to blood ratios vary from about 1 (for
      acetaminophen, amphetamine) to about 2000 (for desmethylclobazam). (3) In certain
      cases (16 over 44), although the drug or its metabolite was not detected in blood
      from different sites, it was detected in bile. As other authors had advocated, it
      is very useful to ask the pathologist to take the gall bladder with its contents
      together with the other samples, in order that the sample of bile can be used in
      the comprehensive toxicological analysis and therefore be complementary to the
      other fluids or matrices. An additional advantage for using bile is that the
      concentrations of drugs or their metabolites are generally several fold higher
      than their blood concentrations.

PMID- 12208020
TI  - Subacute fatal aluminum poisoning in dialyzed patients: post-mortem toxicological
      findings.
AB  - The population of Curacao, Netherlands Antilles (133,000) shows a very high
      prevalence of end-stage renal disease (approximately 1 per 1,000). These patients
      are often treated chronically with haemodialysis. As the drinking water on the
      island is prepared by distillation of sea water, the haemodialysis fluid used to
      be prepared with tap water without further treatment. In 1996, the 27 patients of
      one of the dialysis centers on the island presented with nausea, vomiting, and
      hypercalcaemia in a short time span, which was initially diagnosed as 'hard water
      syndrome'. In spite of treatment with low-calcium dialysate, microcytic anaemia
      and neurological symptoms developed. Ten patients died of convulsions, sepsis,
      and coma. As aluminum (Al) intoxication was suspected, Al in serum (AlS) was
      measured. Ante mortem AlS was 808 microg/l (n = 7; range 359-1189); in the
      survivors AlS was 255 microg/l (n = 17; range 113-490). Normal AlS is < 10
      microg/l, and <50 microg/l in asymptomatic dialyzed patients. The court requested
      post-mortem toxicological analysis of four patients. Al concentrations in liver,
      bone, and cerebral cortex were significantly increased as compared with
      background levels. Al intoxication was, therefore, considered to be the most
      likely cause of death in these patients. Investigations of the tap water supply
      revealed that a few weeks before the onset of the symptoms, a water conduit pipe
      to the dialysis unit had been replaced, which was lined with Al- and Ca-rich
      cement mortar. These ions leached into the distilled water and caused both Ca-
      and Al-intoxication through uptake from the dialysate into the patients'
      circulation. The symptoms of the latter were initially not recognized as they
      were masked by the symptoms of hypercalcaemia.

PMID- 12208021
TI  - Glycated hemoglobin: a useful post-mortem reference marker in determining
      diabetes.
AB  - Glycated hemoglobin (HbA(1c)) has been demonstrated to be a useful marker for
      long-term glucose control in diabetes. This parameter characterizes each non
      enzymatic fixation of glucose on hemoglobin. It is a useful test in addition to
      periodic glycemia controls since it reflects the mean glycemia of the past 60
      days. We studied the conservation of HbA(1c) at 4 degrees C as a function of time
      with different anti-coagulants and preservatives (3, 6 months, 1 year). A total
      of 106 tests were performed using the high performance liquid chromatography
      (HPLC) method dedicated to the semi-automatic analysis of HbA(1c) (Bio-Rad) and
      we applied the method in forensic cases. Conservation at 4 degrees C was good for
      as long as 3 months in blood samples collected with fluoride and 6 months in
      samples collected in a dry or in a heparinized tube. In non-diabetic subjects,
      HbA(1c) reference values obtained from forensic samples were identical to those
      of living controls (3.5-6.25% of total hemoglobin). All positive HbA(1c) results
      were confirmed by a medical evaluation. This method was successfully applied to
      five forensic cases. In cases of increased acetonemia, acetone or isopropanol are
      easily measured. However, in some unexplained post-mortem circumstances,
      increased HbA(1c) permits to differentiate alcoholic or starvation ketoacidosis
      from the diabetic cases. Glycated hemoglobin should, therefore, be considered the
      forensic marker of choice in the post-mortem diagnosis of a diabetic disorder and
      demonstrates its usefulness in post-mortem validation.

PMID- 12208022
TI  - Collective poisoning with hallucinogenous herbal tea.
AB  - An incident wherein more than 30 people were poisoned with a herbal infusion
      during a meditation session is described. The clinical features observed were
      hallucinations, aggression, agitation, amnesia, mydriasis, dry skin, tachycardia,
      hyperthermia, hypotension, collapse, coma and respiratory depression. All
      patients recovered, although mechanical ventilation was required in some
      instances. A portion of the herbal infusion was found to contain atropine
      (hyoscyamine), scopolamine (hyoscine), harmine, and other alkaloids. The
      estimated ingested doses (free bases) were atropine 4 mg, harmine 27 mg, and
      scopolamine 78 mg. The mean concentrations in 21 serum samples obtained
      approximately 6h after ingestion of the infusion were atropine 5 ng/ml, harmine 8
      ng/ml, and scopolamine 13 ng/ml.

PMID- 12208023
TI  - Determination of CDT, a marker of chronic alcohol abuse, for driving license
      issuing: immunoassay versus capillary electrophoresis.
AB  - The present work is aimed at a validation of the carbohydrate-deficient
      transferrin (CDT) determination in real cases by comparison between the a
      commercial immunometric method and a method based on capillary electrophoresis.
      Overall, 650 serum samples from subjects applying to re-obtain their driving
      license, previously withdrawn for "drunk driving", were investigated. A highly
      significant correlation (P < 0.001) was found between the results from
      immunoassay and capillary electrophoresis. However, particularly in the samples
      with CDT values around the cut-off or moderately elevated, a wide dispersion of
      the correlation data was found. This finding stresses the need to confirm by
      alternative techniques all the results from CDT immunoassays. For this purpose,
      capillary electrophoresis, because of its inherent characteristics of high
      selectivity, easy operation, high productivity and low operative costs looks well
      suited for becoming the method of choice.

PMID- 12208024
TI  - Determination of ethyl glucuronide in human hair by SPE and LC-MS/MS.
AB  - A method for the sensitive and selective determination of ethyl glucuronide (EtG)
      in hair has been developed using solid-phase extraction (SPE) and liquid
      chromatography-tandem mass spectrometry (LC-MS/MS). Washed and cut hair segments
      were extracted by ultrasonication (3h, 50 degrees C) and the extracts were
      cleaned-up with aminopropyl SPE columns. LC-MS/MS analysis was performed using a
      polar-endcapped phenyl-hexyl-RP-phase with negative mode electrospray ionisation
      (ESI) using a triple quadrupole mass spectrometer (Sciex API 365) with a
      turboionspray source and post-column addition of acetonitrile for enhanced
      sensitivity. The MS/MS transitions monitored were m/z 221 -->75 for EtG and 226 -
      >75 for D(5)-EtG as an internal standard. The method was selective and sensitive,
      with a detection limit of 51 pg/mg hair at a signal-to-noise ratio of 3:1. The
      mean recovery was 96%, with an intra- and inter-day precision of less than 11.7%
      at a concentration of 200 pg/mg. The linearity was assessed in the range of 25
      2000 pg/mg hair, with a correlation coefficient of 0.997. The method was
      successfully applied to 97 human hair samples which were taken at autopsies from
      persons with known alcoholism or were obtained from alcoholics who were
      hospitalized for ethanol withdrawal, from social drinkers and from children
      having not consumed any alcohol. Although, approximately two-third of the
      alcoholics showed EtG concentrations in hair of higher than 51 pg/mg (up to >4000
      pg/mg), in one-third the EtG concentration was below the detection limit.
      However, only in one of five hair samples of "social drinkers", the EtG
      concentration was above the detection limit (51 pg/mg). No EtG has been detected
      in the hair of children. These investigations demonstrate that heavy alcohol
      consumption may be but not necessarily has to be detectable by EtG analysis in
      hair.

PMID- 12208025
TI  - Hair analysis for delta(9)-THC, delta(9)-THC-COOH, CBN and CBD, by GC/MS-EI.
      Comparison with GC/MS-NCI for delta(9)-THC-COOH.
AB  - A sensitive analytical method was developed for quantitative analysis of delta(9)
      tetrahydrocannabinol (delta(9)-THC), 11-nor-delta(9)-tetrahydrocannabinol
      carboxylic acid (delta(9)-THC-COOH), cannabinol (CBN) and cannabidiol (CBD) in
      human hair. The identification of delta(9)-THC-COOH in hair would document
      Cannabis use more effectively than the detection of parent drug (delta(9)-THC)
      which might have come from environmental exposure. Ketamine was added to hair
      samples as internal standard for CBN and CBD. Ketoprofen was added to hair
      samples as internal standard for the other compounds. Samples were hydrolyzed
      with beta-glucuronidase/arylsulfatase for 2h at 40 degrees C. After cooling,
      samples were extracted with a liquid-liquid extraction procedure (with
      chloroform/isopropyl alcohol, after alkalinization, and n-hexane/ethyl acetate,
      after acidification), which was developed in our laboratory. The extracts were
      analysed before and after derivatization with pentafluoropropionic anhydride
      (PFPA) and pentafluoropropanol (PFPOH) using a Hewlett Packard gas
      chromatographer/mass spectrometer detector, in electron impact mode (GC/MS-EI).
      Derivatized delta(9)-THC-COOH was also analysed using a Hewlett Packard gas
      chromatographer/mass spectrometer detector, in negative ion chemical ionization
      mode (GC/MS-NCI) using methane as the reagent gas. Responses were linear ranging
      from 0.10 to 5.00 ng/mg hair for delta(9)-THC and CBN, 0.10-10.00 ng/mg hair for
      CBD, 0.01-5.00 ng/mg for delta(9)-THC-COOH (r(2)>0.99). The intra-assay
      precisions ranged from <0.01 to 12.40%. Extraction recoveries ranged from 80.9 to
      104.0% for delta(9)-THC, 85.9-100.0% for delta(9)-THC-COOH, 76.7-95.8% for CBN
      and 71.0-94.0% for CBD. The analytical method was applied to 87 human hair
      samples, obtained from individuals who testified in court of having committed
      drug related crimes. Quantification of delta(9)-THC-COOH using GC/MS-NCI was
      found to be more convenient than GC/MS-EI. The latter may give rise to false
      negatives due to the detection limit.

PMID- 12208026
TI  - Hair analysis for opiates, cocaine and metabolites. Evaluation of a method by
      interlaboratory comparison.
AB  - The aim of this study was to evaluate the performance of a technique for the
      simultaneous testing of opiates, cocaine and metabolites in hair by
      interlaboratory comparison. Sixteen forensic and clinical laboratories with
      different degrees of experience in hair analysis participated voluntarily in the
      study (no selection criteria were applied). The suggested analytical procedure,
      the one routinely used in our laboratory, consisted of incubation in HCl 0.1N (45
      degrees C, overnight), solid phase extraction (with Bond Elut Certify)
      cartridges), derivatisation (trimethylsilyl (TMS) derivatives) and GC-MS
      analysis. Three different mixtures of finely cut (1 mm or less) hair were
      prepared using drug-users' and drug-free hair: one 'negative' sample (<0.1 ng/mg
      for morphine, 6-acetylmorphine (6AM), cocaine and benzoylecgonine (BE)), one 'low
      concentration' sample (between 0.5 and 2 ng/mg) and one 'high concentration'
      sample (>3 ng/mg). Accuracy and precision (CV% lower than 5.1, 9.9, 5.2, 3.8, 7.3
      and 8.3% for morphine, 6AM, codeine, cocaine, BE, and methylecgonine (ME),
      respectively; range 0.5-5 ng/mg) of the method and homogeneity of the mixtures
      were evaluated in our laboratory by intraday (CV% lower than 12% for all
      analytes) and interday analyses (CV% lower than 17% for all analytes except 6AM,
      25%). Participants in the study were grouped into: (1) laboratories (n = 6)
      obtaining the best qualitative and quantitative values, corresponding to those
      with long experience in hair analysis; (2) laboratories (n = 5) with no reported
      false positive and/or false negatives; (3) laboratories (n = 5) with one or more
      reported false positives/false negatives. The results obtained by the labs of the
      first group were used as reference values. The scatter of data was similar to
      those obtained in other published studies.

PMID- 12208027
TI  - Quantitation using GC-TOF-MS: example of bromazepam.
AB  - Time-of-flight mass spectrometry (TOF-MS) offers new perspectives for forensic
      toxicology. Qualitative and quantitative analyses of a mixture of three selected
      benzodiazepines (diazepam, nordazepam and bromazepam) were used to compare gas
      chromatography (GC-TOF-MS, quadrupole GC-MS, GC-ECD) and liquid chromatography
      (HPLC-DAD) data. Method validation parameters like LOD, LOQ, S/N-ratios reflect
      the capabilities of GC-TOF-MS. Five-point calibrations for bromazepam in human
      peripheral blood (50, 100, 160, 200, 300 ng/ml) using medazepam as internal
      standard (1000 ng/ml) were performed. The calibrations using GC-TOF-MS (using the
      fragments of m/z 236 and 288), GC-ECD (dual system) and HPLC-DAD (at 235 nm) all
      showed correlation coefficients close or superior to 0.99. Quadrupole GC-MS data
      was not used in the comparison of extracted samples due to the low sensitivity in
      the full scan mode. Two analyses of real cases concerning bromazepam are
      presented. In the first case, the presence or absence of bromazepam could not be
      established with both HPLC-DAD and GC-ECD due to background signals. The
      extracted ion chromatograms and spectrum traces after the analysis with the GC
      TOF-MS could clearly excluded the presence of bromazepam. The second case
      illustrates the quantitation of bromazepam, where both HPLC-DAD and GC-ECD were
      unable to give satisfactory results, again due to interfering background signals.
      The analyses performed on the GC-TOF-MS-system demonstrated high sensitivity and
      also high selectivity due to the high quality of mass spectra obtained. The
      advantages of GC-TOF-MS make it a promising analytical technique for forensic
      toxicology.

PMID- 12208028
TI  - Plasma, oral fluid and sweat wipe ecstasy concentrations in controlled and real
      life conditions.
AB  - In a double-blind placebo controlled study on psychomotor skills important for
      car driving (Study 1), a 75 mg dose of +/- 3,4-methylenedioxymethamphetamine
      (MDMA) was administered orally to 12 healthy volunteers who were known to be
      recreational MDMA-users. Toxicokinetic data were gathered by analysis of blood,
      urine, oral fluid and sweat wipes collected during the first 5h after
      administration. Resultant plasma concentrations varied from 21 to 295 ng/ml, with
      an average peak concentration of 178 ng/ml observed between 2 and 4h after
      administration. MDA concentrations never exceeded 20 ng/ml. Corresponding MDMA
      concentrations in oral fluid, as measured with a specific LC-MS/MS method (which
      required only 50 microl of oral fluid), generally exceeded those in plasma and
      peaked at an average concentration of 1215 ng/ml. A substantial intra- and inter
      subject variability was observed with this matrix, and values ranged from 50 to
      6982 ng/ml MDMA. Somewhat surprisingly, even 4-5h after ingestion, the MDMA
      levels in sweat only averaged 25 ng/wipe. In addition to this controlled study,
      data were collected from 19 MDMA-users who participated in a driving simulator
      study (Study 2), comparing sober non-drug conditions with MDMA-only and multiple
      drug use conditions. In this particular study, urine samples were used for
      general drug screening and oral fluid was collected as an alternative to blood
      sampling. Analysis of oral fluid samples by LC-MS/MS revealed an average
      MDMA/MDEA concentration of 1121 ng/ml in the MDMA-only condition, with large
      inter-subject variability. This was also the case in the multiple drug condition,
      where generally, significantly higher concentrations of MDMA, MDEA and/or
      amphetamine were detected in the oral fluid samples. Urine screening revealed the
      presence of combinations such as MDMA, MDEA, amph, cannabis, cocaine, LSD and
      psilocine in the multiple-drug condition.

PMID- 12208029
TI  - External quality assessment schemes for toxicology.
AB  - A variety of external quality assurance (EQA) schemes monitor quantitative
      performance for routine biochemical analysis of agents such as paracetamol,
      salicylate, ethanol and carboxyhaemoglobin. Their usefulness for toxicologists
      can be lessened where the concentrations monitored do not extend fully into the
      toxic range or where the matrix is synthetic, of animal origin or serum as
      opposed to whole human blood. A scheme for quantitative determinations of a wider
      range of toxicological analytes such as opioids, benzodiazepines and tricyclics
      in human blood has been piloted by the United Kingdom National External Quality
      Assessment Scheme (UKNEQAS). Specialist schemes are available for drugs of abuse
      testing in urine and for hair analysis. Whilst these programmes provide much
      useful information on the performance of analytical techniques, they fail to
      monitor the integrated processes that are needed in investigation of
      toxicological cases. In practice, both qualitative and quantitative tests are
      used in combination with case information to guide the evaluation of the samples
      and to develop an interpretation of the analytical findings that is used to
      provide clinical or forensic advice. EQA programs that combine the analytical and
      interpretative aspects of case studies are available from EQA providers such as
      UKNEQAS and the Dutch KKGT program (Stichting Kwaliteitsbewaking Klinische
      Geneesmiddelanalyse en Toxicologie).

PMID- 12208030
TI  - Mitogenic potential inducible by He:Ne laser in human lymphocytes in vitro.
AB  - The objective of the study was to investigate the mitogenic and genotoxic effects
      of He:Ne laser irradiation (632.8 nm) on human peripheral lymphocytes in vitro.
      We used the cytokinesis-block micronucleus assay, which incorporates cytochalasin
      B to inhibit cytokinesis while karyokinesis proceeds normally leading to the
      appearance of proliferating lymphocytes as binucleated cells. Also micronuclei
      will appear in cases of genotoxicologically-affected cells. Buffy coat leukocytes
      were exposed to 10 mW He:Ne laser at energy densities of 1, 2, 3 and 5 J/cm(2).
      Cells were then cultured in media 199 without any supplementation for 24, 48, 72
      and 96 h adding cytochalasin B 24 h before harvesting of cells. Our results
      showed that laser-induced lymphocytes proliferate throughout the four consecutive
      days post-laser irradiation. The difference in the frequency of micronuclei
      between pre- and post-laser irradiation indicates that a He:Ne laser at such
      energy densities 1, 2, 3 and 5 J/cm(2) does not induce micronucleus formation.
      These results shed some light on the mechanism encountered by lymphocytes in the
      process of He:Ne laser-induced biostimulation.

PMID- 12208031
TI  - Timing of 5-aminolaevulinic acid-induced photodynamic therapy for the treatment
      of patients with Barrett's oesophagus.
AB  - 5-Aminolaevulinic acid-induced photodynamic therapy (ALA-PDT) is being used as an
      experimental treatment of Barrett's oesophagus (BE), a pre-malignant disorder in
      the distal oesophagus. The present study aims to acquire detailed knowledge on
      the pharmacokinetics of ALA and the photosensitizer protoporphyin IX (PPIX) in
      tissues and plasma of patients with BE to provide a rationale for the conditions
      used in ALA-PDT. A total of 26 patients with BE were randomized to varying time
      intervals between ingesting 60 mg/kg ALA and undergoing an endoscopy with
      biopsies of BE, normal oesophageal and gastric mucosa. At 1, 2, 7, 8 and 24 h,
      two patients at each time, and at 3, 4, 5 and 6 h, four patients at each time
      after ALA ingestion were included. ALA, porphyrin intermediates and PPIX were
      determined in all biopsy and plasma samples. The maximum concentration of PPIX
      was found earlier in BE (4.6+/-0.5 h) than in squamous epithelium (SQ) (6.6+/-2.2
      h) (P<0.05). PPIX concentrations were higher in SQ than in BE especially at
      longer time intervals. In addition, tissue ALA concentrations were found to be 20
      fold higher than the plasma concentrations at 1 h after ALA ingestion, suggesting
      uptake from the oesophageal lumen. Skin photosensitivity was short-lasting but
      often debilitating. Our results provide a rationale for the use of ALA-PDT for
      the treatment of BE at 4-5 h after ALA ingestion and for local application of ALA
      in the oesophagus. Patients undergoing ALA-PDT must be strongly advised to avoid
      sunlight for at least 24-36 h.

PMID- 12208032
TI  - Photophysical and photosensitizing properties of selected cyanines.
AB  - The present work has been carried out to obtain detailed information about the
      photophysical and photobiological properties of selected cyanines, in view of
      their possible use as photosensitizing agents. All the cyanines studied by us
      except CY-IV (3,3'-diethyl-4,4'-oxacarbocyanine), expressed an accelerated
      photobleaching in aqueous medium, a poor generation of singlet oxygen, and a
      relative weak photosensitizing activity towards albumin. On the cellular level,
      all cyanines exhibited a significant phototoxicity towards Balb/c 3T3 cells, upon
      irradiation with a total fluence of 30 J/cm(2). CY-III (3,3'
      diethylcarbothiocayanine iodide) and CY-II (1,1'-diethyl-4,4'-carbocyanine
      iodide) appear to be promising photosensitizers, in spite of previous reports on
      the inefficiency of the former cyanine, and the rapid photobleaching of the
      latter compound.

PMID- 12208033
TI  - Influence of ice and snow covers on the UV exposure of terrestrial microbial
      communities: dosimetric studies.
AB  - Bacillus subtilis spore biological dosimeters and electronic dosimeters were used
      to investigate the exposure of terrestrial microbial communities in micro
      habitats covered by snow and ice in Antarctica. The melting of snow covers of
      between 5- and 15-cm thickness, depending on age and heterogeneity, could
      increase B. subtilis spore inactivation by up to an order of magnitude, a
      relative increase twice that caused by a 50% ozone depletion. Within the snow
      pack at depths of less than approximately 3 cm snow algae could receive two to
      three times the DNA-weighted irradiance they would receive on bare ground. At the
      edge of the snow-pack, warming of low albedo soils resulted in the formation of
      overhangs that provided transient UV protection to thawed and growing microbial
      communities on the soils underneath. In shallow aquatic habitats, thin layers of
      heterogeneous ice of a few millimetres thickness were found to reduce DNA
      weighted irradiances by up to 55% compared to full-sky values with equivalent DNA
      weighted diffuse attenuation coefficients (K(DNA)) of >200 m(-1). A 2-mm snow
      encrusted ice cover on a pond was equivalent to 10 cm of ice on a perennially ice
      covered lake. Ice covers also had the effect of stabilizing the UV exposure,
      which was often subject to rapid variations of up to 33% of the mean value caused
      by wind-rippling of the water surface. These data show that changing ice and snow
      covers cause relative changes in microbial UV exposure at least as great as those
      caused by changing ozone column abundance.

PMID- 12208034
TI  - Preparation and biological evaluation of the new chlorin photosensitizer T3,4BCPC
      for detection and treatment of tumors.
AB  - The new water-soluble photosensitizer 5,10,15,20-tetrakis[3,4
      bis(carboxymethyleneoxy)phenyl]chlorin (T3,4BCPC) has been prepared,
      characterized and labeled with 99mTc radionuclide. The radiotracer was evaluated
      for tissue distribution in Wistar rats. Accumulation of administrated activities
      in the liver, kidney, bladder and large intestine at 4 h post-injection indicated
      that the labeled ligand was largely eliminated through the renal and partly
      through the hepatobiliary system. In vivo biodistribution studies of the labeled
      compound were carried out in rodent and murine tumor models in comparison with
      other tumor-seeking radiopharmaceuticals such as 99mTc(V)-dimercaptosuccinic acid
      (DMSA), 201thallous chloride (TlCl) and 99mTc-citrate using a gamma camera
      computer system. In N-nitrosomethylurea (NMU)-induced rat mammary tumors, the
      labeled ligand showed a five-fold tumor to muscle (T/M) ratio compared to
      99mTc(V)-DMSA (3-fold) and 201TlCl (3-fold). In the case of C(3)H/J virus-induced
      spontaneous mammary tumors, the differences were not marked. However, in the
      transplanted rat C(6)-glioma, the T/M ratio of the labeled compound was
      appreciably higher (four-fold) than that noted with 99mTc(V)-DMSA (two-fold),
      201TlCl (three-fold) and 99mTc-citrate (more than three-fold). These findings
      suggest that the radiolabeled T3,4BCPC may have potential for the detection of
      cancer. In order to ascertain the efficacy of the compound for photodynamic
      therapy applications, a preclinical PDT study was carried out in fibrosarcoma
      bearing mice after injecting 5.0 mg/kg body weight of the T3,4BCPC. A laser dose
      of 20 mW for 60 s resulted in 80% destruction of tumors. These data suggest that
      this molecule could be useful for PDT of cancer. The labeled agent could also be
      useful in monitoring the progression/regression of tumors before, during, and
      after chemotherapy, radiation therapy or PDT.

PMID- 12208035
TI  - Xanthophyll pigments lutein and zeaxanthin in lipid multibilayers formed with
      dimyristoylphosphatidylcholine.
AB  - This paper reports the research on the effect of two main carotenoid pigments
      present in the membranes of macula lutea of the vision apparatus of primates,
      including humans, lutein and zeaxanthin, on the structure of model membranes
      formed with dimyristoylphosphatidylcholine (DMPC). The effects observed in DMPC
      are compared to the effects observed in the membranes formed with other
      phosphatidylcholines (PC): egg yolk PC (EYPC), and dipalmitoyl-PC (DPPC). The
      analysis has been focused, in particular, on the following aspects of the
      organization of lipid-carotenoid membranes: aggregation state of pigments, an
      effect on a thickness of the bilayer and pigment orientation within the
      membranes. These problems have been addressed with the application of UV-Vis
      absorption spectroscopy, linear dichroism measurements and the diffractometric
      technique. (1) Both lutein and zeaxanthin appear in a partially aggregated form
      in the oriented DMPC multibilayers, even at molar fractions as low as 2 mol.%
      with respect to lipid. (2) Orientation of the transition dipole of both
      xanthophylls with respect to the axis normal to the plane of DMPC membrane is
      different in the case of a monomeric form (34+/-3 degrees in the case of lutein
      and 26+/-3 degrees in the case of zeaxanthin) but essentially the same in the
      case of aggregated forms of both pigments (42+/-3 degrees in the case of lutein
      and 40+/-5 degrees in the case of zeaxanthin). It was found that only lutein has
      an effect on the increase in the thickness of the DMPC membranes (by about 3 A at
      25 degrees C). A similar effect was observed also in the case of DPPC at the same
      temperatures despite the differences in the physical state of both membrane
      systems. The differences between the effects of lutein and zeaxanthin observed
      are interpreted in terms of differences of stereochemical structure of both
      xanthophylls leading to the different localization in the lipid phase. The
      results demonstrate significant differences in the behavior of lutein and
      zeaxanthin in model membranes, which may contribute to their different
      physiological functions and different efficacy as membrane antioxidants.

PMID- 12208036
TI  - Misclassification due to body hair and seasonal variation on melanin density
      estimates for skin type using spectrophotometry.
AB  - Recent advances have enabled quite accurate estimations of cutaneous melanin
      density by spectrophotometry using reflectance of light at wavelengths 400 and
      420 nm. Our purpose was to assess the effect of body hair and seasonal variation
      at the upper inner arm and buttock on measurements of melanin density. We
      estimated melanin density of 104 volunteers at 3-monthly intervals over 12 months
      both before and after shaving. Removing body hair at the upper inner arm had no
      effect, but substantially reduced melanin estimates at the buttock in men.
      Significant seasonal variation was only observed at the upper inner arm, with
      highest readings in summer-autumn. In case-control studies, misclassification due
      to body hair at the buttock and seasonal variation at the upper inner arm could
      affect the observed odds ratio substantially. However, both sources of error can
      be reduced by careful attention to key aspects of study design.

PMID- 12208037
TI  - A computational study of physical and biological characterization of common UV
      sources and filters, and their relevance for substituting sunlight.
AB  - Sunlight is the most important environmental UV source, affecting not only human
      health but also the whole terrestrial ecosystem. The use of artificial sources is
      advantageous since it is independent of geographical location and seasonal
      variations, however, in some photobiological/photochemical studies the choice of
      a specific UV source in relation to the biological end-point studied is sometimes
      questionable. Furthermore, it is often difficult to compare the results obtained
      in different laboratories due to 'slight' differences in the physical
      characteristics of the UV sources used. In an attempt to address these issues we
      calculated and compared the physical characteristics and the biological
      efficiency in UV-B and UV-A regions for two biological end-points (CPD and Fpg
      sensitive sites formation) for frequently used UV-B, UV-A sources and solar light
      simulators (SLS). Our calculation shows that FS20 lamp is appropriate for
      studying the biological effects of UV-B radiation although differences in
      spectral characteristics of the associated filters may lead to at least 2-fold
      yields in CPD production. Furthermore, the use of a SLS with a Kodacel filter
      alone is inadequate for studying environmental UV effects. A metal-halide source
      with a Schott WG345 filter is appropriate for studies on biological effects due
      to UV-A region. Relative exposure duration was calculated to achieve equal amount
      of CPD or Fpg-sensitive sites, provided equal, total UV-(A+B) irradiance for the
      different UV sources.

PMID- 12208038
TI  - Presence of human Giardia in domestic, farm and wild animals, and environmental
      samples suggests a zoonotic potential for giardiasis.
AB  - Giardia lamblia which parasitize humans belong to either of two genotypes, A or
      B, based on specific signature sequences in the 5' end of the small subunit (16S)
      ribosomal RNA (rRNA) gene. These two genotypes also were found in cysts from
      fecal samples of animal origin such as dogs, cats, some farm animals and wild
      animals. In addition, trophozoites recovered from cysts obtained from
      environmental samples belonged to these two genotypes as well, suggesting that
      the G. lamblia genotypes A and B are widespread and possibly zoonotic.
      Trophozoites were recovered from rats and these isolates might belong to another
      genotype of G. lamblia. Deer mice and one dog appeared to be parasitized by
      genotypes of Giardia with close affinity to G. microti. This species, therefore,
      also consists of a genotype complex.

PMID- 12208039
TI  - An epidemiological study on ovine babesiosis in the Mashhad suburb area, province
      of Khorasan, Iran.
AB  - The prevalence of Babesia spp. infection was studied in sheep of the Mashhad area
      in Iran from 1998 to 2000. A total of 677 sheep originating from 115 flocks were
      clinically examined and investigated for the presence of Babesia spp. in
      appropriate blood smears and any tick species on the body of the animals. The
      study revealed that the infection rate for Babesia ovis and Babesia motasi were
      167 (24.6%) and 4 (0.5%), respectively. Double (mixed) infections occurred in 21
      (3%) sheep. Differences in infection rates were statistically non-significant
      between male and female sheep and between different age groups. Seasonally, the
      prevalence of Babesia spp. infection started to increase in April and reached
      highest values in August (56%), while a decrease was observed in September,
      reaching the lowest levels In February and March. The study demonstrated that
      1.7% of sheep infected with B. ovis and 50% of sheep infected with B. motasi
      exhibited clinical signs. Sheep infected with B. motasi showed the highest levels
      of parasitemia. We found that 550 (73%) of the animals harbored Rhipicephalus
      sanguineus; 166 (21%) Hyalomma marginatum; 19 (2.5%) Dermacentor daghestanicus;
      14 (1.8%) Hyalomma anatolicum; 6 (0.66%) Hyalomma asiaticum; and one (0.13%)
      Haemaphysalis punctata. The examination of 727 tick haemolymph samples and 52
      tick egg smears showed that one sample (0.2%) of haemolymph of R. sanguineus, two
      (1.2%) haemolymphs of H. marginatum and two (2%) eggs of R. sanguineus harbored
      kinetes morphologically matching the criteria described for B. ovis.

PMID- 12208040
TI  - Susceptibility of trypanotolerant West African Dwarf goats and F1 crosses with
      the susceptible Sahelian breed to experimental Trypanosoma congolense infection
      and interactions with helminth infections and different levels of diet.
AB  - Forty pure West African Dwarf (WAD) goats and 35 of its F1 crosses with the
      Sahelian breed were used in a multifactorial experimental design to evaluate the
      effects of an experimental Trypanosoma congolense infection and interactions with
      natural helminth infections and different levels of diet on health and
      productivity of these two breeds. Trypanosome infection caused a severe drop in
      packed cell volume (PCV), but this was not significantly affected by breed.
      Neither deworming nor diet had any effect on the course of anaemia after
      trypanosome infection. The mean score of parasitaemia tended to be higher in
      crossbreeds than in WAD goats although this was not significant (P>0.05).
      Similarly, the antibody response to trypanosome infection was not significantly
      different between breeds. Parasitaemia level was significantly influenced by the
      level of diet with the group under high supplementation having a higher mean
      parasitaemia score than the group under low supplementation. Weight loss due to
      trypanosome infection tended to be greater in crossbreeds than in WAD goats
      (P>0.05). During this study, there was no difference in mean helminth egg output
      between crossbred and WAD goats. However, between weeks 4 and 10 after
      trypanosome infection (corresponding to a period of heavy rainfall and highly
      infective pastures), the mean egg output was higher in the crossbreeds. The
      immunosuppressive effect of trypanosome infections was revealed by a lower
      antibody response to Haemonchus contortus in infected animals compared to the
      uninfected controls. Trypanosome infection tended to increase strongyle egg
      output. This study did no reveal any superior trypanotolerance of WAD goats
      compared to crossbreeds.

PMID- 12208041
TI  - A cross-sectional coprological survey of liver flukes in cattle and sheep from an
      area of the southern Italian Apennines.
AB  - A cross-sectional coprological survey of liver flukes (Fasciola hepatica and
      Dicrocoelium dendriticum) was conducted on 81 bovine farms and 197 ovine farms
      with animals pasturing in an area (3971 km(2)) of the southern Italian Apennines.
      The farms were selected to be uniformly distributed throughout the study area
      using geographical information system (GIS) software. Between June 1999 and March
      2000, faecal samples were collected from 975 cattle and 3940 sheep and examined
      using a modified McMaster technique. The results were subjected to statistical
      analysis and point distribution maps (PDMs) were drawn by GIS. Cattle of 9 of the
      81 (11.1%) farms were positive for F. hepatica and of 43 (53.1%) for D.
      dendriticum. Sheep of 8 of the 197 (4.1%) farms were positive for F. hepatica and
      of 133 (67.5%) for D. dendriticum. Co-infection was found in cattle of 2 (2.5%)
      farms, and in sheep of 8 (4.1%) farms. The findings of the present survey show
      that D. dendriticum was the predominant liver fluke found in cattle and sheep
      with respect to egg count numbers for both farms and animals. In addition, the
      general trends of the PDMs show that D. dendriticum was widely and homogeneously
      spread throughout the study area, whereas F. hepatica was present only in a few
      concentrated zones of the study area that had both positive bovine and positive
      ovine farms.

PMID- 12208042
TI  - Subcutaneous infection of Lagochilascaris minor in domestic cats from Uruguay.
AB  - The nematode Lagochilascaris minor was collected from subcutaneous abscesses on
      the face and neck of three female cats aged 8 months, and 1 and 2 years. These
      cats were born in the Department of Maldonado, Uruguay. Female and male nematodes
      were 10.1-14.4 and 10.0-14.3mm long, respectively. The lips were one dorsal lip
      and two subventral lips separated from the body by a deep post-labial groove, and
      were separated from each other by triangular interlabial projections. The width
      of the lips was almost equal to the width of the post-labial collar. The vulva
      was near the middle of the female body. The eggs were oval or spherical and
      measured 0.059-0.073 mm long and 0.045-0.065 mm wide. Irregular-shaped pits were
      on the egg surface; 20-32 pits were around the equator of the eggs. The male
      posterior region was ventrally curved. Each spicule was about three quarters of
      the ejaculator duct length. From these findings, the nematodes were identified as
      L. minor. We believe this is the first report of its infection in Uruguay.

PMID- 12208043
TI  - Molecular phylogenetic analysis of Onchocerca lupi and its Wolbachia
      endosymbiont.
AB  - The morphology of Onchocerca lupi, responsible for canine ocular onchocercosis,
      is unique within the genus. Earlier analyses of the 5S ribosomal RNA gene spacer
      region sequence of the parasite and the 16S ribosomal RNA gene sequence of its
      Wolbachia endosymbiotic bacteria (Rickettsiales) supported the morphological and
      biological arguments that O. lupi is a distinct species. However, the exact
      phylogenetic position of O. lupi and its endosymbiont could not be unambiguously
      determined. Herein we report analyses based on the mitochondrial cytochrome
      oxidase I (COI) gene of the filarial species and the Wolbachia surface protein
      (wsp) and the bacterial cell-cycle ftsZ genes of their wolbachiae. Our results
      indicate that O. lupi separated from other Onchocerca spp. early in evolution.
      This is in line with the previous morphological analysis demonstrating that O.
      lupi is an atypical Onchocerca species showing both primitive and evolved
      characters. The phylogenetic trees generated for the COI sequences of filariae
      and the wsp and ftsZ sequences of their wolbachiae were congruent with each
      other, which supports the hypothesis that nematodes and their Wolbachia
      endobacteria share a long co-evolutionary history.

PMID- 12208044
TI  - Evaluation of ELISA and Western Blot Analysis using three antigens to detect anti
      Trichinella IgG in horses.
AB  - We assessed a serological method for detecting Trichinella infection in horses,
      specifically, an ELISA using three antigens to detect anti-Trichinella IgG (i.e.
      a synthetic tyvelose glycan-BSA (stg-BSA) antigen, an excretory/secretory (ES)
      antigen, and a crude worm extract (CWE) antigen). Serum samples were collected
      from 2502 horses (433 live horses from Romania and 2069 horses slaughtered in
      Italy and originating from Italy, Poland, Romania, and Serbia). Serum samples
      were also taken from horses experimentally infected with different doses of T.
      spiralis and T. murrelli larvae, as controls. The cut-off value of ELISA was
      determined on serum samples from 330 horses from Trichinella-free regions of
      Italy, which were also examined by artificial digestion of preferential-muscle
      samples. In the experimentally infected horses, the stg-BSA and ES antigens were
      less sensitive than the CWE antigen. Trichinella spiralis showed a higher
      immunogenicity than T. murrelli, and the IgG immunoresponse was dose-dependent.
      The kinetics of anti-Trichinella IgG were similar among all experimentally
      infected horses. No circulating antibodies were detected 4-5 months after
      experimental infection, although these horses still harbored infective larvae.
      Depending on the antigen used, for 4-7 of the 330 horses from Trichinella-free
      areas, the optical density (OD) of the serum sample was higher than the cut-off
      value, yet these samples were negative when subjected to Western Blot. Similar
      results were obtained for the 1739 horses slaughtered in Italy (originating from
      Italy, Poland, Romania, and Serbia) and the 433 live Romanian horses. Of the 4
      horses with muscle larvae, only one was positive by ELISA and Western Blot.
      Because the anti-Trichinella IgG remain circulating for only a short period of
      time, whereas the larvae remain infective for longer periods, serology cannot be
      used for either diagnosing Trichinella infection in horses or estimating the
      prevalence of infection. Artificial digestion of at least 5 g of preferential
      muscle tissue continues to be the method of choice at the slaughterhouse for
      preventing equine-borne trichinellosis in humans.

PMID- 12208045
TI  - Diagnosis of equine piroplasmosis in Xinjiang province of China by the enzyme
      linked immunosorbent assays using recombinant antigens.
AB  - The prevalence of equine piroplasmosis in Xinjiang province, China, was examined
      by enzyme-linked immunosorbent assays (ELISAs). A total of 70 serum samples were
      taken from horses pastured on three farms in western Xinjiang, and examined for
      diagnosis of equine Babesia equi (B. equi) infection and B. caballi infection by
      ELISAs using recombinant equi merozoite antigen 1 (EMA-1) and recombinant P48
      antigen, respectively. Of the 70 samples, 28 (40.0%) and 17 (24.3%) samples were
      positive for B. equi infection and B. caballi infection, respectively. In
      addition, 11 (15.7%) samples were positive for both B. equi and B. caballi
      infections. These results indicate that equine piroplasmosis is widespread and
      therefore a cause for serious concern in western Xinjiang. To our knowledge, this
      is the first report describing a survey on equine piroplasmosis in Xinjiang
      province, China.

PMID- 12208046
TI  - DNA vaccination in the avian.
AB  - Inoculation of naked DNA represents a novel approach to vaccine and immune
      therapeutic development. DNA vaccines or genetic immunization offers several
      advantages over the conventional vaccines for specific immune activation.
      Although a large number of vaccines have been made and are being used in the
      poultry industry, there have been no major advances in vaccine technology for
      this animal industry sector for decades. The potential advantages of DNA
      vaccines, such as over coming maternal immunity, in ovo delivery and absence of
      requirement for a cold-chain, combined with immunological efficacy make this new
      vaccine technology very attractive for the poultry industry. This review lists
      all of the published reports of experimental DNA vaccines developed for use in
      poultry and focuses on the trends, potentials and remaining barriers in the
      development of this new revolution in poultry vaccinology.

PMID- 12208047
TI  - Cloning, expression, purification, and biological activity of five feline type I
      interferons.
AB  - Type I interferons (IFN) are important mediators of the host defense against
      viral infections in mammals. In humans multiple subtypes of IFN-alpha exist, most
      of which possess antiviral activity. Little is known about the type I IFN genes
      in cats and the role they may play in feline immunological responses to viruses.
      We have isolated cDNAs encoding five feline IFN-alpha (feIFN) subtypes that share
      from 95 to 99% amino acid sequence identity. FeIFN-alpha5 has five additional
      amino acids inserted at position 139, which are not present in the other four
      subtypes. Sequence identity of the feIFN proteins encoded by the five clones
      compared to human IFN-alpha2 is approximately 60%. Unlike most of the human
      subtypes, each of the five feline IFN sequences has an N-glycosylation
      recognition site. Expression of all five feIFN-alpha subtypes in Chinese hamster
      ovary (CHO) cells was confirmed by Western blot analysis, and all resulting
      proteins were glycosylated. The antiviral activity of each feIFN-alpha subtype
      produced in transiently transfected CHO cell cultures was tested in vitro. In
      addition, subtype feIFN-alpha6 was expressed in the yeast, Pichia pastoris. The
      resulting secreted mature recombinant protein was purified and demonstrated
      significant antiviral activity and induction of 2',5'-oligoadenylate synthetase
      activity in vitro.

PMID- 12208048
TI  - Effects of phenoxyethanol on the innate immune system of gilthead seabream
      (Sparus aurata L.) exposed to crowding stress.
AB  - Phenoxyethanol is routinely used in seabream aquaculture to minimise fish stress
      response despite the secondary negative effects which have been observed. In this
      study, two different doses (60 and 200 microl/l) of phenoxyethanol, sedative and
      narcotic, were tested for their ability to reduce the stress caused in gilthead
      seabream (Sparus aurata L.) by crowding. Blood glucose and serum cortisol
      concentrations were measured as stress indicators. In order to study the effects
      of the treatment on the innate immune system of crowded specimens, two parameters
      of the innate immune response, serum complement activity and phagocytosis, were
      assessed. The results show that anaesthesia itself produced a stress response in
      the fish and affected the immune system, although the effects were greater with
      the narcotic dose. When the effects of anaesthesia on crowded fish were analysed,
      the results pointed to a slight reduction in stress as a result of the sedative
      dose of phenoxyethanol (lower increase in cortisol and lower reduction in
      phagocytosis). However, additive negative effects were seen in crowded fish when
      the narcotic dose of phenoxyethanol was used. Since the use of phenoxyethanol is
      a common practice in aquaculture, the significance of the results should be
      considered.

PMID- 12208049
TI  - Cloning and expression of the ovine CD40 molecule and the inhibition of the mixed
      lymphocyte reaction by the ovine CD40(e)-EGFP fusion protein.
AB  - The CD40 molecule is a member of the tumour necrosis factor receptor (TNFR)-like
      supergene family and plays a major role as a co-stimulatory molecule in the
      activation of T cells in response to antigens presented by dendritic cells. In
      this study, reverse transcription-PCR cloning was used to derive the sequence
      encoding ovine CD40. The ovine CD40 sequence demonstrated a similarity of 97, 76
      and 64% with the bovine, human and murine sequences, respectively, at the nucleic
      acid level. The cysteine residues characteristic of the TNFR family and N-linked
      glycosylation sites are conserved. Furthermore, RNA analysis confirmed expression
      of CD40 mRNA in both ovine dendritic cells from lymphatic drainage and dermal
      fibroblasts in culture. In addition, cDNA encompassing the extracellular region
      of ovine CD40 (CD40(e)) was fused 'in-frame' with the enhanced green fluorescent
      protein (EGFP) to generate a fusion protein upon the transfection of Chinese
      hamster ovary (CHO) cells. Immunoprecipitation with an anti-GFP monoclonal
      antibody of a 78 kD a protein from conditioned medium of CHO transfectants
      confirmed that the CD40(e)-EGFP was secreted in the supernatant. All experiments
      were controlled with a pEGFP-N1 vector-blank construct. Moreover, the biological
      activity of ovine CD40(e)-EGFP was demonstrated by its ability to inhibit a two
      way mixed lymphocyte reaction. Thus these observations confirm that ovine CD40
      blockade inhibits co-stimulation mediated by CD40-CD40L (CD154) interactions as
      has been reported in murine and human studies.

PMID- 12208050
TI  - Immunological differences between layer- and broiler-type chickens.
AB  - In commercial poultry husbandry, alternatives for the use of antibiotics and
      vaccines are under investigation, which preferably have to be applicable for both
      layer- and broiler-type chickens. There are indications that the defense
      mechanisms vary between layer- and broiler-type chickens. Therefore, the
      difference in immune response between layer- and broiler-type chickens of the
      same age was investigated, using TNP-KLH (trinitrophenyl-conjugated keyhole
      limpet hemocyanin) as antigen without adjuvant. First different routes of
      immunization (intravenously, intramuscular, subcutaneous and ocular) were
      examined to find out which immunization route gives the highest antibody titers.
      The intravenous immunization route resulted in higher TNP-specific antibody
      responses than the other immunization routes tested and therefore this
      immunization route was used in both following experiments. In order to
      investigate the optimal dose of antigen needed for immunization, a dose-response
      curve in broiler- and layer-type chickens was completed. The humoral immune
      response was measured in serum by a TNP-specific ELISA and the in vitro cellular
      immune response by an antigen-specific lymphocyte proliferation assay. The
      antibody response of layer- and broiler-type chickens appeared to differ, not
      only in optimal dose and response, but also in kinetics of the response itself.
      Broiler chickens generated higher IgM anti-TNP titers whereas layer-type chickens
      generated higher IgG anti-TNP titers. This specific antibody response in broiler
      type chickens did not last as long as in layer-type chickens. The TNP-specific
      cellular immune response was detectable in layer-type chickens, but not in
      broilers. Both types generate a non-specific cellular immune response, although
      this response in broilers is lower than in layer-type chickens. From these
      results, we conclude that broilers primarily respond to TNP-KLH with a high IgM
      antibody response whereas layer-type chickens respond with a high IgG response.
      In addition, the cellular response of layer-type chickens is much higher than the
      response of broilers. The results suggest that broilers are specialized in the
      production of a strong short-term humoral response and layer-type chickens in a
      long-term humoral response in combination with a strong cellular response, which
      is in conformity with their life expectancy.

PMID- 12208051
TI  - Immunological responses of the lactating ovine udder following experimental
      challenge with Staphylococcus epidermidis.
AB  - The responses of five lactating ewes to experimental mammary infection with
      Staphylococcus epidermidis were examined. Infection caused an intense but
      transient influx of neutrophils into milk, which peaked at 8 h and was
      accompanied by mild fever and mild leukopaenia in blood. No other signs of
      systemic infection were observed. Number of staphylococci in milk decreased
      logarithmically until 24 h, were absent from three ewes at 48 h and then
      increased in number or re-emerged in four of the five ewes at 72 or 144 h. At all
      times milk appeared grossly normal. Expression of the adhesion molecules CD11b
      and CD18 increased on neutrophils in milk at 24 h then tended to decline over
      subsequent days. The proportion of lymphocytes positive for CD4, CD8, WC1 and
      MHCII tended to decrease from 24 to 72 h then increased at 144 h. Cytokines in
      milk were measured by ELISA. IL-8 was elevated in infected glands at 2 h, peaked
      at 24 h and remained elevated until the final sampling at 144 h. IL-6 was
      transiently elevated at 4 and 8 h while IL-1beta remained elevated from 8 until
      144 h. The results suggest that the intense early neutrophil infiltrate
      eliminated most but not all bacteria and a state of subclinical infection ensued.
      After 24 h , leukocyte numbers in milk declined while cytokines, especially IL-8
      remained elevated, suggesting that sensitivity or responsiveness of gland to
      inflammatory signals decreased as infection progressed. This attenuation of the
      host defence response may have contributed to the failure of the gland to
      eliminate bacteria and may be an important feature of the development of chronic
      and subclinical mastitis.

PMID- 12208052
TI  - A novel transcutaneous plasmid-dimethylsulfoxide delivery technique for avian
      nucleic acid immunization.
AB  - In this report, we show that dimethylsulfoxide (DMSO) enhances liposome-mediated
      transfection of nucleic acid in chicken macrophage cells and that this could be
      exploited for the transcutaneous delivery of naked DNA through the intact skin of
      chickens. We found that DMSO enhanced transfection efficiencies of lipofectamine
      and polyethyleneimine in HD-11 chicken macrophage cells. Based on this principle,
      we showed that transcutaneous delivery of a DNA plasmid-dimethylsulfoxide mixture
      (1:1) to untreated skin of chickens results in a wide distribution of the plasmid
      in the body. Distribution studies were done using plasmids encoding enhanced
      green fluorescent protein (EGFP) reporter gene and a bivalent DNA vaccine coding
      for infectious bursal disease virus (IBDV) and Newcastle disease virus (NDV)
      immunogenic protein genes. This bivalent vaccine induced mucosal and systemic
      immune responses, as evidenced by IgA and IgM production in the tears and serum
      of vaccinated chickens. Mucosal immune responses in the tears after topical
      vaccination were significantly higher (P < 0.05) than after i.m. delivery of the
      same DNA vaccine and were characterized by the absence of an IgG response. The
      biodistribution of plasmid indicated that topical delivery with DMSO resulted in
      a wide distribution and persistence of the plasmid until 15 weeks post-primary
      vaccination. Both delivery methods resulted in insert-specific message being made
      in several body tissues, but after topical delivery the virus-specific mRNA could
      be detected in the bone marrow of one out of three chickens until 15 weeks post
      primary vaccination. Furthermore, transcutaneous delivery of this DNA vaccine
      using DMSO conferred protection from challenge with virulent IBDV (86% survival)
      and NDV (86% survival). This novel transcutaneous method of delivery of a DNA
      vaccine shows promise as being an easy and effective way to deliver nucleic acids
      through intact skin for vaccination or therapeutic purposes.

PMID- 12208053
TI  - Graft-versus-host reaction (GVHR) in clonal amago salmon, Oncorhynchus rhodurus.
AB  - The graft-versus-host reaction (GVHR) was demonstrated in a salmonid model system
      of clonal diploid and triploid amago salmon. Triploid operculum grafts on clonal
      diploid evoked an acute rejection within 12 days. Grafts exchanged among triploid
      amago salmon exhibited prolonged survival for 18 days. In contrast, diploid
      grafts on triploid, and allografts among clonal diploid amago salmon were
      accepted. A typical GVHR was induced in triploid recipients by intraperitonal
      injection of head kidney cells from sensitised diploid donors. The clinical signs
      of graft-versus-host disease (GVHD) were observed in the recipients after 1 week
      of cell injection as a loss of appetite and appearance of solid faeces, followed
      by haemorrhage, local swelling of ventral skin and an enlarged spleen. Three of
      six fish died within 1 month. Water temperature and frequency of sensitisation
      are critical to induce GVHR. Diploid donors had to be sensitised three times at
      20 degrees C to induce the typical GVHR. GVHR was most effectively induced by
      head kidney cells, followed by peripheral blood leucocytes (PBL) and spleen
      cells. Ploidy analysis by flow cytometry revealed that the donor head kidney
      cells greatly increased in the recipient liver, head kidney and spleen, and
      reached the peak after 9 days of donor cell injection. The results in the present
      study are quite similar to the findings in ginbuna and ginbuna-gold fish hybrid
      system, suggesting the presence of T cells in salmonid as well as cyprinid fish.

PMID- 12208054
TI  - Isolation and characterization of immortalized porcine aortic endothelial cell
      lines.
AB  - Primary porcine endothelial cells have a limited life span in culture. After four
      to five passages, they tend to de-differentiate and eventually reach senescence.
      The aim of this work was to establish immortalized porcine aortic endothelial
      cell lines (AOCs) to facilitate in vitro studies of different pathological
      process involving the endothelium. Primary porcine aortic endothelial cells
      (PAECs) were transfected with a plasmid containing the SV40 genome and selected
      on the basis of morphological and phenotypical features. Flow cytometry analysis
      demonstrated uptake of acetylated low density lipoproteins (Ac-LDL) and
      constitutive expression of SLA class I, CD29, CD31, CD41/61, CD80/86, CD46, SWC3,
      and LAMP-1 antigens by all analyzed lines and showed little differences to
      primary cells. The functional similarity between primary and immortalized
      endothelial cells was demonstrated in a cytotoxicity assay using a human natural
      killer cell line (NKL) as effector. The AOCs cell lines should be valuable tools
      for in vitro study of the human immune response against pig endothelial cells. In
      addition, they would be very useful to gain insight in the pathogenesis of some
      viral haemorrhagic diseases of pig such as African swine fever (ASF) or classical
      swine fever (CSF).

PMID- 12208055
TI  - A rapid and simple method for the separation of pure lymphocytes from horse
      blood.
AB  - A method for the separation of pure and viable lymphocytes and granulocytes from
      the same blood sample in horses was reported. By centrifuging equine heparinized
      blood at 100 xg for 10 min at room temperature (r.t.), the resulting supernatant
      plasma was an almost pure (97.71 +/- 0.30%; n = 15) suspension of highly viable
      (98.72 +/- 0.28%) lymphocytes. When sodium citrate was used as an anticoagulant,
      lymphocyte suspensions collected in the same manner showed lower purity (87.89 +/
      1.59%; n = 9) and higher yields (56.56 +/- 3.89%, n = 9 versus 36.11 +/- 2.23%,
      n = 15). Where needed, a further centrifugation at 250 xg for 3 min (r.t.) of
      heparinized lymphocyte preparations removed an average of 87.39% (n = 15)
      contaminating platelets. A suspension of 85.96 +/- 2.20% pure granulocytes (93.23
      +/- 1.74% neutrophils; n = 14) with minimal contamination by erythrocytes and
      high viability (93.11 +/- 1.26%) was obtained by performing a flash red blood
      cell lysis on the white-greyish layer resulting from the centrifugation of the
      heparinized blood samples. Among the several methods available, the procedure
      described herein is easy, rapid, cheap and reproducible.

PMID- 12208056
TI  - Trauma deaths in an Italian urban area: an audit of pre-hospital and in-hospital
      trauma care.
AB  - In Italy, a comprehensive regional study of trauma deaths has never been
      performed. We examined the organization and delivery of trauma care in the city
      area of Milan, using panel review of trauma deaths. Two panels evaluated the
      appropriateness of care of all trauma victims occurred during 1 year, applying
      predefined criteria and judging deaths as not preventable (NP), possible
      preventable (PP), and definitely preventable (DP). Two hundred and fifty-five
      deaths were reviewed. Blunt trauma were 78.04% and motor vehicle crashes
      accounted for over 50%. Most victims (73.72%) died during pre-hospital settings
      and 91.1% died within the first 6h, principally because of central nervous system
      injuries in blunt and hemorrhage in penetrating trauma. Panels judged 57% of
      deaths NP, 32% PP, 11% DP (inter-panel K-test 0.88). Preventable deaths were
      higher after in-hospital admission. Main failures of treatment were lack in
      airway control or intravenous infusions in pre-hospital and mismanagement with
      missed injuries in emergency department. The high rate of avoidable deaths in
      Milan supports the need of trained pre-hospital personnel and of well equipped
      referring hospitals for trauma.

PMID- 12208057
TI  - Injury patterns in skiboarding. A 2-year study in Scotland.
AB  - OBJECTIVES: To examine the incidence and patterns of injury associated with
      skiboarding, a new snow sport whose popularity has increased in recent years.
      METHODS: A prospective study of all injured skiboarders at Cairngorm, Glenshee
      and Nevis Range ski areas during the 1999-2000 and 2000-2001 winter seasons.
      Personal details, skiboarding parameters, diagnosis and treatment were recorded.
      Random counts were performed to analyse the percentage of skiboarders amongst the
      on-slope population. RESULTS: The 84 injuries were recorded in 80 individuals.
      The injury rate for skiboarding was 252 mean days between injury (MDBI).
      Skiboarders comprised 5% of the total on-slope population. Ligament sprains and
      fractures accounted for 49 and 36% of all injuries, respectively. Over 70% of all
      injuries affected the lower limb and 21% of injuries were below knee fractures.
      The incidence of upper limb injuries was lower than expected at 13% of total.
      CONCLUSIONS: Skiboarding, whilst not associated with an excess injury rate, has a
      unique pattern of injury with a higher fracture rate than any other snow sport.
      The rates of lower limb and upper limb injury may be explained by the use of a
      non-release binding and inherent differences in the nature of a skiboard fall.

PMID- 12208058
TI  - Whiplash injury--a retrospective study on patients seeking compensation.
AB  - The purpose of this cohort study is to evaluate the objective long-term findings
      and the final outcome of a population suffering from whiplash-associated
      disorders (WAD) after rear-end car collision and claiming legal compensation.
      Eight hundred and sixty-six patients after whiplash injury were followed up on
      average 32 months post-trauma. All patients had clinical examination and
      radiographs performed on the day of the accident and at follow up. MRI, CT scan,
      bone scan, electromyographic (EMG) tests were performed upon request of the
      treating physician and correlated by the authors with the clinical findings.
      Cervical pain was the most common complaint (96%). Radiating pain to one side of
      the upper limbs or the shoulder was also very common (36 and 24%, respectively).
      Chin to chest test was found to be a strong indicator in differentiating between
      the less severe (grades 1 and 2) to more severe (grades 3 and 4) WAD patients. In
      10% of the patients with normal radiographic findings, degenerative changes were
      found at follow up. CT scan and MRI did not add to patient diagnosis, except for
      those patients suffering from degenerative changes and decreased range of motion
      (RoM). Based on our findings the initial radiograph taken in the emergency room
      was the best imaging modality and probably the only one needed routinely
      following whiplash injury. Although this is a special subgroup of patient seeking
      compensation, the overall prognosis is favorable in all grades of WAD injury and
      there is no need for further diagnostic expenditures.

PMID- 12208060
TI  - Low lumbar spinal fractures: management options.
AB  - Fifty-four patients with low lumbar spinal fractures were retrospectively
      reviewed. Of these, there were 25 compression fractures, 21 burst fractures,
      three flexion-distraction fractures and five fracture-dislocations. Three
      patients had a complete neurological lesion, 17 sustained an incomplete
      neurological injury, and 34 were neurologically intact. Twenty-six patients were
      treated non-operatively and 28 underwent surgery. All patients were followed up
      for l-12 years. Forty-three patients (79.6%) have returned to their former
      employment or activity level. Four patients had experienced significant
      improvement but suffered from some limitation of activity. Five patients were
      unable to stand up and walk without support although they had some degree of
      improvement. Two remained completely paralyzed. There were no differences in
      neurologic function between patients treated non-operatively or operatively
      (P>0.05). The patients treated operatively had significantly less pain compared
      to the patients treated non-operatively (P<0.01). Because of the unique anatomy
      and biomechanics, fractures of the low lumbar spine are different from those in
      the remaining regions of spine. Most compression fractures are stable, and
      therefore conservative management is indicated. Surgery should be performed in
      those with burst fractures or flexion-distraction fractures, with severe spinal
      stenosis or kyphotic deformity, and fracture-dislocation.

PMID- 12208059
TI  - Failure to administer methylprednisolone for acute traumatic spinal cord injury-a
      prospective audit of 100 patients from a regional spinal injuries unit.
AB  - OVERVIEW: The National Acute Spinal Cord Injury Studies (NASCIS II and III) and
      the Cochrane review advocate the administration of high dose methylprednisolone
      following acute traumatic spinal cord injury. OBJECTIVE: To determine the actual
      use and correct implementation of the NASCIS protocols in patients referred to a
      regional spinal injuries unit. DESIGN: Observational study on the timing and
      correct dosage of methylprednisolone. The admission Frankel grade, American
      Spinal Injury Association (ASIA) neurological classification were recorded
      prospectively. SUBJECTS: The 100 consecutive patients with complete or incomplete
      spinal cord injuries (Frankel grade A-D) were studied over a 2 years period. MAIN
      OUTCOME MEASURE: Correct administration of methylprednisolone according to the
      NASCIS protocols. RESULTS: During the study period only 25% of the patients
      admitted to our spinal injuries unit received methylprednisolone at the referring
      hospital according to the NASCIS protocols. An additional 10 patients were given
      methylprednisolone incorrectly. CONCLUSION: Evidence based medicine is not being
      practiced in the management of patients with acute spinal cord injury.

PMID- 12208061
TI  - Late lower extremity fractures in patients with paraplegia.
AB  - We report the result of the treatment of 26 lower limb fractures in patients with
      established paraplegia. We treated one fracture of the femoral neck, one
      intertrochanteric, two subtrochanteric, two of the femoral shaft, seven of the
      supracondylar region, six of the proximal tibia, one of the tibial shaft, and six
      pilon fractures. Nine fractures were treated non-operatively, and the remaining
      fractures were treated operatively. Union was achieved in all the patients, but
      we think that open reduction and internal fixation may improve the level of
      independence and mobility of these patients during fracture healing.

PMID- 12208062
TI  - The prevalence of spinal trauma associated with brachial plexus injuries.
AB  - Severe closed traction lesions to the adult brachial plexus are caused by high
      energy transfer injuries, in which injuries to other systems are common. Of the
      149 patients urgently operated on for lesions of the brachial plexus between 1
      June 1997 and 1999, 18 (12%) suffered significant injury to the spinal column.
      Accurate diagnosis of the spinal injury was made in 13 cases of these before
      transfer to our unit.The injury to the spine was not necessarily a
      contraindication to urgent exploration of the brachial plexus.

PMID- 12208063
TI  - The comparison of electrophysiologic findings of traumatic brachial plexopathies
      in a tertiary care center.
AB  - This study was undertaken to demonstrate the distribution of causative factors of
      brachial plexopathy (BP), to assess the association between the mechanism of
      injuries and the predominant level of the brachial plexus involved in the
      injuries, and to characterize the extent and degree of severity of injury in
      patients with BPI. It consisted of a cross-sectional, retrospective review of
      electrophysiological data of 5547 patients with 117 patients being identified as
      having BPI, of whom 86 patients were recruited into the study. The patients were
      divided into six subgroups according to the mechanism of the damage. The injury
      was subdivided according to the brachial plexus levels predominantly affected,
      and each component of the four major anatomical plexus levels-root, trunk, cord
      and nerve levels was analyzed. The affiliation between the type of injuries and
      the specified brachial plexus levels was calculated via a two-tailed Fisher's
      exact test. These findings demonstrated that the type of brachial plexus injury
      (BPI) is significantly related to the brachial plexus level involved. The
      motorcycle and birth injury groups were affected at the trunk level, the fall
      group at the nerve level, the automobile group at the cord level, and the blunt
      injury group at the cord or nerve level. Moreover, the majority of patients in
      the motorcycle, fall, and pedestrian groups suffered from severe, incomplete
      lesions, while the neurophysiological results of the other groups varied.

PMID- 12208064
TI  - Transposition of local muscles to restore elbow flexion in brachial plexus palsy.
AB  - Between 1994 and 2001, triceps to biceps transfers were done in 10 men and a
      transfer of the forearm flexors and extensors (Steindler procedure) in nine. All
      had suffered from a post-traumatic lesion of their brachial plexus, resulting in
      loss of elbow flexion. Their mean age at the time of the original accident was 27
      years (range 16-50 years) and at the time of muscle transfer 35 years (range 22
      56 years), with a mean observation period of 20 months (range 6-51 months). In 16
      patients, a neurosurgical procedure had been performed after the trauma, and in
      22 patients other reconstructive operations had been done. Transfer of the
      forearm flexors and extensors resulted in active elbow flexion with a mean of 94
      degrees (range 70-130 degrees ). After triceps to biceps transposition a mean of
      109 degrees (range 70-140 degrees ) was reached. A mean deficit of passive
      extension of 12 degrees (range 0-30 degrees ) remained after the Steindler
      procedure, and of 5 degrees (range 0-10 degrees ) after triceps to biceps
      transposition. Two complications occurred with the Steindler procedure. The
      transfer of the triceps muscle to the tendon of the biceps and the transfer of
      the forearm flexors or extensors on loss of elbow flexion, therefore, resulted in
      adequate movement and strength. Both procedures involve operating close to the
      elbow joint and had minimal complications. The triceps to biceps transfer is
      particularly suitable for co-contraction of triceps and biceps.

PMID- 12208065
TI  - Duodenal injuries: surgical management adapted to circumstances.
AB  - OBJECTIVES: To evaluate the results of an evolving policy of primary repair of
      duodenal injuries, when considered feasible and safe, complemented by pyloric
      exclusion if any doubt as to the integrity of the repair existed. PATIENTS AND
      METHODS: A prospective analysis of all patients with surgically identified
      duodenal injuries treated at a single institution over a 3-year period. RESULTS:
      In 30 patients studied, there were four deaths (13%) and an overall complication
      rate of 47%. There were 68 associated intra-abdominal injuries in 29 patients.
      Primary duodenorraphy was employed in 18 patients (60%), pyloric exclusion in 11
      (37%) and pancreatoduodenectomy in one patient (3%). No failures of duodenal
      repair were recorded. CONCLUSION: Adverse results in patients with duodenal
      trauma are largely a reflection of frequent associated injuries and their
      consequences. Selective, liberal employment of pyloric exclusion, based on
      individualized intra-operative assessment, can minimize duodenum-related
      morbidity.

PMID- 12208066
TI  - Intra-abdominal gastrointestinal tract injuries following blunt trauma: the
      experience of an Australian trauma centre.
AB  - AIMS: The aim of the study was to use the extensive experience of an Australian
      Level I trauma centre to develop guidelines for diagnosis and management of
      significant gastrointestinal tract injuries (GITIs). METHODS: This was a
      retrospective study of 74 patients admitted to Westmead Hospital between 1985 and
      1996 who had sustained major gastrointestinal tract (GIT) injuries following
      blunt trauma. The patients were identified from the trauma unit database.
      Clinical information was retrieved from the database and augmented by a review of
      the medical records. RESULTS: Motor vehicle accidents were responsible for 55
      (92%) admissions. Laparotomy was performed as a result of a positive diagnostic
      peritoneal lavage in 26 (35.1%) patients, abdominal signs in 20 (27%), diagnostic
      findings on computed tomography in 19 (25.7%), haemodynamic instability in eight
      (10.8%) and a positive contrast study in one (1.4%) patient. There was a total of
      95 injuries: one gastric (1.1%), eight duodenal (8.4%), 64 small bowel (67.3%),
      two appendiceal (2.1%), 19 colonic (20%) and one rectal (1.1%). Thirty day
      mortality was 23% (17 patients). Seven (9.5%) patients died within 24h of injury,
      three (4.1%) of which were directly related to the GIT. Ten (13.5%) patients died
      within 2 weeks of admission, three (4.1%) of which were attributable to the GIT.
      Thirty day GIT morbidity was 29.7% (22 patients). The development of GIT
      morbidity was significantly related to a delay to laparotomy of more than 24h
      (P=0.036) and tachycardia on presentation (P=0.023). Associated injuries, injury
      severity scores (ISS) and age did not significantly impact on GITI related
      morbidity and mortality. DISCUSSION: Major GITIs are associated with a high
      mortality due to the severity and complexity of associated injuries. Morbidity
      from GITIs correlates to delays in diagnosis and management.

PMID- 12208067
TI  - Peripheral nerve reconstruction by autograft.
AB  - The purpose of this retrospective clinical study was to present the results
      achieved by microsurgical reconstruction of peripheral nerve injuries in the 15
      years between 1985 and 1999. Sixty patients underwent 63 surgical procedures.
      Forty-five nerves were reconstructed by autograft in 42 patients with injuries of
      the upper extremities; 14 patients had lower limb peripheral nerve
      reconstruction. The facial nerve was reconstructed by autograft in four patients.
      Factors that could possibly affect the results, such as delaying surgery, age of
      the patient, nature of the injury, length of the autograft, height of the injury
      and type of nerve damage, were assessed. The results were better in the
      reconstruction of nerve injuries in the upper than the lower limbs.
      Reconstruction of the tibial nerve was also rewarding. In general, the results of
      facial nerve reconstruction were good. The time between injury and reconstructive
      surgery was a crucial factor for successful outcome, especially in younger
      patients.

PMID- 12208068
TI  - Segmental fracture of the dens.

PMID- 12208069
TI  - Self inflicted neck injury with an electric drill.

PMID- 12208070
TI  - Traumatic thoracobiliary fistulae: a case report with a review of the current
      management options.

PMID- 12208071
TI  - Choledochal cyst and blunt trauma--case report.

PMID- 12208072
TI  - An alternative technique for the delayed primary closure of traumatic wounds.

PMID- 12208073
TI  - Vertex haematoma and paraplegia.

PMID- 12208074
TI  - Differential gene expression of vascular endothelial growth factor isoforms and
      their receptors in the development of the rat masseter muscle.
AB  - The capillary network in the masseter muscle develops dramatically with the
      differentiation of muscle fibres after birth, especially around weaning. Here,
      developmental changes in mRNA expression for four splicing variants of vascular
      endothelial growth factor (VEGF) and for two distinct VEGF receptors (Fms-like
      tyrosine kinase (Flt-1) and kinase insert domain-containing receptor/fetal liver
      kinase-1 (KDR/Flk-1)) were studied in rat masseter. The relative abundance of
      VEGF (120) mRNA was the highest, representing 35% of total VEGF mRNA on day 7
      after birth and gradually decreased with age to become approximately 5% on day
      37. In contrast, VEGF (188) mRNA was very low in the newborn rat, but increased
      sharply before weaning and reached 40-50% of the total on day 50. Neither VEGF
      (144) nor VEGF(164) mRNA showed any significant change in abundance after birth.
      The expression of KDR/Flk-1 mRNA was transiently high in the early postnatal
      stage and gradually decreased with age, Flt-1 mRNA was stably expressed at a
      constant level after birth. These findings suggest that different combinations of
      VEGF isoforms and their receptors regulate angiogenesis in the development of the
      masseter muscle.

PMID- 12208075
TI  - Differential expression of the Fas-Fas ligand system on cytokine-induced
      apoptotic cell death in mouse osteoblastic cells.
AB  - Apoptotic signalling, particularly in the Fas-Fas ligand (FasL) system, was
      studied in a mouse osteoblastic cell line, MC3T3-E1. A combination of the
      cytokines tumour necrosis factor-alpha, interleukin-1beta and interferon-gamma
      activated the Fas-FasL-dependent cell-death system. The cytokines caused
      significant enhancement of Fas mRNA and Fas protein, and led to apoptotic cell
      death. Western blot demonstrated that FasL protein was continuously present in
      MC3T3-E1 cells, although the cytokines had no effect on the induction of FasL.
      Exogenous FasL caused a decrease in cell viability and a large increase in
      apoptotic cell death in cells pre-treated with cytokines, indicating that the Fas
      FasL system has the potential to cause apoptosis in osteoblastic cells. Treatment
      with anti-Fas IgG (antagonistic antibody) inhibited the DNA fragmentation induced
      by cytokines in a dose-dependent manner, suggesting that cytokine-induced Fas may
      cause apoptotic cell death in MC3T3-E1 cells. Taken together, these findings show
      that cytokine-induced apoptotic cell death was mediated by the autocrine or
      paracrine Fas-FasL system in mouse osteoblastic cells, and suggest that cytokine
      induced apoptosis could have an important role in localised bone destruction
      associated with inflammatory bone diseases such as periodontal disease.

PMID- 12208076
TI  - A histomorphometric study of adaptive responses of cancellous bone in different
      regions in the sheep mandibular condyle following experimental forward mandibular
      displacement.
AB  - Forward mandibular displacement in animal models is associated with faster and/or
      redirected condylar growth. Here the effect of forward displacement induced with
      an intraoral appliance on modelling/remodelling of the mandibular condyle was
      investigated in eight, 4-month-old, castrated male Merino sheep, randomly
      allocated to experimental and control groups (n=4 in each group). The study
      period was 15 weeks, during that time, (1). calcein, (2). tetracycline, and (3).
      alizarin red S fluorochromes were given to all animals from day 1. Midsagittal
      sections of the temporomandibular joints were selected for analysis. Dynamic
      variables of bone formation, static indices of bone-forming and -resorbing
      activity, and structural indices of trabecular bone were estimated
      histomorphometrically. The sampling site was divided into two regions for
      analysis: (a). a 'subchondral region' (2 and 3 labels only), believed to be the
      bone newly formed during the experimental period; (b). a 'central region'
      (labelled by all three fluorochromes), believed to be the bone that existed
      before the experiment. Regional differences in adaptive response were found. In
      the experimental group, the bone-volume fraction (BV/TV) of the subchondral
      regions had decreased, although the specific bone-surface and bone-formation
      rates had increased. This low BV/TV was associated with decreased trabecular
      thickness and increased trabecular separation. In the central condylar region of
      the experimental group, BV/TV was unchanged, but an increased osteoid surface was
      apparent when the eroded surface was taken into consideration. These adaptive
      condylar responses to forward mandibular displacement appeared to be the result
      of increased osteoblastic activity. Further studies are recommended to examine
      why the subchondral and central regions responded differently.

PMID- 12208077
TI  - Oxygen distribution and consumption in rat lower incisor pulp.
AB  - The aim was to determine the oxygen tension (P(O(2))) and rate of oxygen
      consumption in the pulp. Twelve rats were anaesthetised and artificially
      ventilated. Under an operating microscope, a recessed oxygen-sensitive
      microelectrode was inserted into the pulp through a small saline-covered cavity
      on the labial surface of the lower incisor. P(O(2)) was measured as a function of
      the transverse distance from the saline medium through to the middle of the pulp.
      Oxygen profiles were characterised by a decline of oxygen tension outside the
      pulp in the saline medium and a steeper gradient across the interface, before a
      localised oxygen consuming region corresponding to the odontoblasts. A plateau
      with some localised fluctuations was then followed by an increase in oxygen
      tension in the middle of the pulp. The average oxygen tension in the plateau
      region was 23.2 mmHg+/-2.1 mmHg (n=12). A mathematical model was used to extract
      oxygen consumption data from P(O(2)) profiles recorded from non-perfused pulp
      (created by reducing systemic blood pressure). The analysis revealed that there
      was a distinct oxygen consumption zone in the outer pulp, which anatomically
      corresponded to the odontoblast layer. The average oxygen consumption rate of the
      odontoblasts was 3.2+/-0.2 ml O(2)/min per 100g pulp tissue. The zone of high
      oxygen consumption was 68.7 micro m+/-6.9 micro m (n=24) thick. It is concluded
      that pulpal oxygen distribution is heterogeneous and that the odontoblast could
      be a major oxygen consumer within the rat incisor pulp.

PMID- 12208078
TI  - Reperfusion response changes induced by repeated, sustained contractions in
      normal human masseter muscle.
AB  - The purpose was to evaluate the intramuscular reperfusion response
      characteristics associated with repeated isometric contractions in normal human
      masseter. Intramuscular blood volume was quantified with a near-infrared
      spectroscopic device that measured the total haemoglobin (Hb) concentration in
      the muscle. Electromyographic (EMG) activity from the masseter and total bite
      forces were also recorded. Sixteen healthy volunteers, eight females and eight
      males, without masticatory muscle pain participated. They were asked first to
      clench their teeth for as long as possible at 50% of their maximum voluntary
      contraction (MVC). This was followed by a 60s rest and then immediately by a
      standard clenching task (50% MVC for 30s) and a 60s recovery period, immediately
      after which they were asked to repeat exactly the same procedure, with a final 5
      min recovery period after the second 30s contraction. Bite force, EMG and Hb
      concentration were measured continuously and the duration of the two endurance
      tasks and the amplitudes of all recorded signals were compared (first trial
      versus second trial). Specifically, the difference between the lowest Hb (trough)
      seen during the standardised 30s contractions and the highest (peak) seen just
      after them was assessed. The trough-to-peak difference in Hb concentration of the
      second standard contraction task was significantly smaller than that of the first
      standard task (P<0.05, paired t-test). These data show that with sustained effort
      the post-contraction vasodilatory reperfusion responses of the human masseter are
      diminished, suggesting a progressive desensitisation of the vasodilatory system.

PMID- 12208079
TI  - Impact of landmark reliability on the planar Procrustes analysis of tooth shape.
AB  - In a recent study, the ideas of Procrustes analysis were introduced to the study
      of tooth shape for teeth represented as configurations of 'landmarks' from
      digital images. This study aimed to establish how well the method could be
      expected to perform (in its standard form) when used on surfaces from a variety
      of tooth types and, in particular, how much impact inconsistencies in the
      positioning of landmarks would have on investigations of shape. Using four
      different operators' images and landmarks from 10 different surfaces from each of
      20 patients, the consequences of location inconsistency are evaluated by
      calculating its effect on the recorded variation in Procrustes fits, obtained for
      each set of multiple representations. The proportion of variation in shape
      attributable to actual differences between patients, rather than other sources of
      error, ranged from only 36 to 65% for the five buccal-surfaces considered and was
      no more than 30% for any of the five occlusal surfaces. Further examination of
      these results indicated that consistent orientation differences before imaging
      might be a particular source of error in obtaining any occlusal-landmark data, as
      might location ambiguities around the edges of the teeth. Orientation effects
      were also suggested for the buccal-surfaces of the molar teeth. In contrast, the
      relatively flatter buccal-surfaces of the incisors and canines produced the most
      reliable data. Methods of analysis need to accommodate these problems if landmark
      data are to be used to describe variations in tooth shape. Different surfaces
      each present their own particular difficulties and so a variety of solutions may
      be required.

PMID- 12208080
TI  - A comparison between a conventional optical method and image-analysis for
      measuring the unimpeded eruption rate of the rat mandibular incisor.
AB  - The impeded/unimpeded eruption rates of the rat incisor have been much studied.
      The most commonly used optical microscopic method, which has inherent weaknesses,
      was compared here with an image-analysis method to measure the eruption rate of
      the mandibular incisor. The study also evaluated the incisal edge as a reference
      point for the measurement of the unimpeded eruption rate, and the frequency of
      shortening the mandibular incisor. The image-analysis method was found to be a
      simple and reliable technique that could replace the optical method. There was no
      significant difference between the data from the two methods; their kappa
      coefficients were similar at the 0.99 level. It was concluded that shortening the
      incisor in the measurement of the unimpeded eruption rate should be done at least
      every 48 h, and that the incisal edge of the shortened incisor can be used as the
      reference point for that measurement.

PMID- 12208081
TI  - Comparison of amylase mRNAs from rat parotid gland, pancreas and liver using
      reverse transcriptase-polymerase chain reaction.
AB  - The expression of mRNA for amylase was examined using the reverse transcriptase
      polymerase chain reaction (RT-PCR). An amylase product was strongly detected in
      parotid and pancreas, but less strongly in liver. The degree of identity between
      the PCR products was assessed by restriction-enzyme mapping using two restriction
      enzymes, EcoRI and ScaI, and DNA sequencing. The PCR product from pancreas was
      cut by both EcoRI and ScaI, while the products from parotid and liver were cut by
      EcoRI but not by ScaI. The sequence of the parotid product was 90.4% homologous
      to that of the pancreas, and 100% homologous to that of the liver. These results
      indicate that the same amylase mRNA may be expressed in parotid and liver. In
      addition, the expression of amylase mRNAs in other rat tissues was investigated
      using RT-PCR, and the sensitivity of each PCR product to ScaI was tested. A weak
      single band was detected in submandibular gland, sublingual gland and stomach.
      ScaI digestion cut the stomach product into two fragments, but had no effect on
      the submandibular and sublingual products. Thus, it may be possible to classify
      amylase isoenzymes into pancreatic and parotid types based on the sensitivity of
      their PCR products to ScaI.

PMID- 12208083
TI  - Responses of C fiber afferents of the rabbit airways and lungs to changes in
      extra-vascular fluid volume.
AB  - Effects of changes in extra-vascular fluid volume produced by pulmonary lymphatic
      obstruction and plasmapheresis on the activities of bronchial and pulmonary C
      fiber receptors and rapidly adapting receptors (RARs) were investigated in New
      Zealand White rabbits. In intact rabbits, pulmonary lymphatic obstruction either
      alone or in combination with plasmapheresis did not stimulate pulmonary C fiber
      receptors. Only the combined stimulus activated the bronchial C fiber receptors.
      Bronchial C fiber receptors were also stimulated by graded increases in left
      atrial pressure (+5 and +10 mmHg). In contrast, RARs were activated by lymphatic
      obstruction either alone or in combination with plasmapheresis. These procedures
      increase the extra-vascular fluid volume in the carina and bronchi but not in the
      lungs (alveoli). In rabbits with chronic pulmonary venous congestion secondary to
      mitral valve damage, bronchial C fiber receptors were not stimulated by these
      increments in left atrial pressure which were insufficient to increase the extra
      vascular fluid content of the airways. However, both pulmonary and bronchial C
      fiber receptors were stimulated when the left atrial pressure was raised to 25
      mmHg in these animals to cause pulmonary edema.

PMID- 12208084
TI  - Serotonin and serotonin receptor expression in the aorta of carotid intact and
      denervated newborns.
AB  - Pharmacological blocking of serotonin (5-HT) 5A receptors abolishes aortic
      ventilatory chemosensitivity of carotid body denervated (CBD) piglets [J. Appl.
      Physiol. 92 (2002) 893]. Accordingly, the purpose of the present study was to
      determine whether 5-HT and 5-HT receptors exist at aortic sites that are
      chemosensitive after CBD. Aortas from CBD and sham CBD rats and piglets and from
      aortic denervated (AOD) and combined AOD+CBD piglets were harvested, sectioned
      and then studied using immunohistochemistry and western blot techniques. 5-HT
      immunoreactivity in piglets and rats was concentrated in the endothelium and sub
      endothelial areas in several aortic regions studied, and in some areas also in
      the adventitia. At the aortic chemosensitive site (descending aorta in CBD
      piglets and the ascending aorta in CBD rats), the immunoreactivity was greater (P
      < 0.05) than in other aortic regions and greater than in other groups studied.
      The 5-HT(5a) receptor was expressed only at the chemosensitive sites and only in
      aortic innervated piglets. We conclude that the data from this and a previous
      study [J. Appl. Physiol. 92 (2002) 893] suggest that a serotonergic mechanism
      contributes to the aortic ventilatory chemoreflex after CBD.

PMID- 12208085
TI  - Neurogenesis of gasping does not require inhibitory transmission using GABA(A) or
      glycine receptors.
AB  - We evaluated the hypothesis that the neurogenesis of gasping is not dependent
      upon inhibitory synaptic transmission involving GABA(A) or glycine receptors.
      Activity of the phrenic nerve was recorded in a perfused juvenile rat
      preparation. The pattern of phrenic activity was altered from eupnea to gasping
      in severe hypoxia or ischaemia. To block GABA(A) receptors, bicuculline or
      picrotoxin was administered. Strychnine was used to block transmission by
      glycine. Following administrations of bicuculline, picrotoxin or strychnine, the
      eupneic rhythm was greatly distorted whereas the decrementing pattern of the gasp
      was maintained. At high concentrations of these antagonists, the frequency of
      gasps was increased and the peak height of gasps fell. We conclude that the
      neurogenesis of gasping is not dependent upon fast, chloride-mediated inhibitory
      synaptic transmission.

PMID- 12208086
TI  - Acetazolamide and respiratory chemosensitivity to CO(2) in the neonatal rat
      transverse medullary slice.
AB  - Hypoglossal nerve rootlets in the transverse medullary slice prepared from
      neonatal rats exhibit a bursting 'respiratory' rhythm that increases in frequency
      with CO(2), presumably due to activation of chemosensitive cells such as the
      central chemoreceptors. Carbonic anhydrase is associated with areas of central
      chemoreception and we propose a hypothesis for its involvement in the
      chemoreception process. We tested this hypothesis by blocking its activity with
      acetazolamide in six slice preparations. However, the addition of 1 mM
      acetazolamide dissolved in dimethyl sulphoxide to the superfusing bathing
      solution produced no alteration in the bursting frequency response of the slice
      to CO(2). We concluded that the chemoreception process producing the CO(2)
      response of the superfused, transverse medullary slice does not involve carbonic
      anhydrase.

PMID- 12208087
TI  - Chemical lesions of the nucleus isthmi increase the hypoxic and hypercarbic drive
      to breathing of toads.
AB  - The nucleus isthmi (NI) is a mesencephalic structure of the amphibian brain that
      has recently been reported to participate in the hypoxic and hypercarbic drive to
      breathing. However, previous studies used electrolytic and kainic lesions, which
      causes diffuse and nonspecific destruction. Thus, in the present study, we
      assessed the participation of NI in the respiratory response to hypoxia and
      hypercarbia using lesions produced with ibotenic acid (a substance that
      selectively destroys cell bodies but spares fibers of passage) into the NI of
      toads (Bufo paracnemis). Our results demonstrated that, under resting breathing,
      NI plays no role in pulmonary ventilation. Hypoxia and hypercarbia caused
      hyperventilation in all groups. Chemical lesions in the NI elicited an increase
      in ventilatory response to hypoxia and hypercarbia, due to a higher tidal volume.
      We conclude that NI cell bodies do not participate in the control of pulmonary
      ventilation under resting conditions, but exert an inhibitory modulation of
      hypoxic and hypercarbic drive to breathing, acting on tidal volume.

PMID- 12208088
TI  - Reproducibility of twitch and sniff transdiaphragmatic pressures.
AB  - Twitch transdiaphragmatic pressure (Tw Pdi) measured with magnetic stimulation of
      the phrenic nerve is used to follow up patients and to assess the effect of
      clinical treatments on diaphragm function. However the reproducibility of Tw Pdi
      on different occasions has been little studied. We investigated 32 normal
      subjects, measuring Tw Pdi elicited by bilateral magnetic stimulation of the
      phrenic nerves on two to 14 occasions. Sniff transdiaphragmatic pressure (sniff
      Pdi) was also measured. The mean value of Tw Pdi and sniff Pdi were 28+/-5 and
      134+/-24 cm H(2)O, respectively. The within subjects coefficient of variation was
      11% for both Tw Pdi and sniff Pdi. We conclude that there is a variability of Tw
      Pdi and the variability of Tw Pdi is the same as that of sniff Pdi.

PMID- 12208089
TI  - Differential effect of epidermal growth factor on serous and mucous cells in
      porcine airway submucosal gland.
AB  - Using a patch-clamp technique, we found that the fresh porcine submucosal gland
      acinar cells contained two functionally distinct cell populations, i.e.
      physiologically relevant concentration of acetylcholine (ACh, 30 nM) induced two
      distinct patterns of electric response in tracheal gland acinar cells. One was
      characterized by an outstanding oscillatory Cl(-)-current activity, and the other
      was with poor Cl(-)-current response but with a comparable K(+)-current. We
      examined the effect of epidermal growth factor (EGF) on the ACh-induced electric
      responses in these cells. EGF affected only the latter (K(+)-prominent) cell type
      to potentiate significantly the ACh-induced K(+)-current. An immunohistochemistry
      revealed that the receptor for EGF was identified preferentially on the mucous,
      but not serous, cells. Genistein, one of the tyrosine-kinase inhibitors,
      abolished the augmentation effect of EGF on the ACh-induced current. Thus, we
      identified the serous cell with a Cl(-)-rich current in response to ACh and the
      mucous cell with a K(+)-dominant response. Moreover, EGF affected the mucous
      cells alone to potentiate the ACh-induced electric response. EGF may contribute
      to the pathophysiological alterations in chronic inflammatory airways both in
      morphological (mucous cell hypertrophy/hyperplasia) and functional (thick viscous
      hypersecretion) ways.

PMID- 12208090
TI  - Secretion movement during manual lung inflation and mechanical ventilation.
AB  - This project aimed to investigate the direction of artificial sputum movement
      during mechanical ventilation (MV) and bagging (MH) using a tube model. Three
      solutions of artificial sputum (ultrasonic gel, viscosity 100, 200 and 300 poise
      (P)) were prepared. About 1 ml of gel was placed in a glass tube connected to a
      test lung at one end and, via a pneumotachograph, to either a mechanical
      ventilator or a self-inflating bag, at the other. The position of the gel in the
      tube was recorded before and after 20 artificial breaths. Simultaneous breath-to
      breath respiratory mechanics were measured. The procedure was repeated three
      times for each gel viscosity, with a fresh experimental set up for each
      measurement. Results showed that the distance travelled from the lung was
      significantly greater with MH compared with MV (P < 0.001). The lower the gel
      viscosity, the further the gel moved from the lung with both ventilatory modes (P
      < 0.001). MH was superior to MV for secretion mobilisation in a tube model.

PMID- 12208091
TI  - Axial and radial distribution of the bronchial vasculature in sheep.
AB  - A morphometric analysis was made on the bronchial vasculature of intrapulmonary
      airways in sheep lungs. This study provides the parameters to calculate the
      quantity of soluble gas diffusion between the vasculature and airways for use in
      a mathematical model describing heat and mass exchange in the lungs. To achieve
      these results, the lungs of four adult sheep (30-36 kg.) were excised, fixed,
      dissected and microtomed to obtain airway cross-sections for measurement. Blood
      vessel size and airway proximity was measured using a microscope interfaced with
      a computer. Distance from airway lumen to most airway vessels ranged from 30 to
      270 microm. It was found that the bronchial vessels surrounding intraparenchymal
      airways can be described by a right-skewed distribution. Most importantly, a
      practical description of the bronchial capillary size and airway proximity as a
      function of airway diameter was found using a weighed average. This analysis
      facilitates calculation of soluble gas flux from the bronchial vasculature to the
      airway for use in a mathematical model.

PMID- 12208092
TI  - In vitro wounding of airway smooth muscle cell monolayers increases expression of
      TGF-beta receptors.
AB  - During an exacerbation of asthma, there is bronchial epithelial cell injury and
      influx of inflammatory cells. In these instances, the release of proteases and
      various cytokines could lead to injury of the airway smooth muscle cells (ASMCs).
      Airway remodeling is a characteristic finding in asthma but the role of ASMC
      injury in remodeling is unknown. Previously, we demonstrated that mechanical
      wounding of confluent monolayers of bovine ASMCs resulted in the release of
      biologically active transforming growth factor-beta1 (TGF-beta1), which in turn,
      induced collagen I expression. In the present study, we demonstrate that after
      mechanical wounding, ASMCs had an increased expression of the signal transducing
      TGF-beta receptors TbetaR-I and TbetaR-II as detected by flow cytometry and
      Western analysis. Corticosteroids are standard therapy in asthma and the presence
      of dexamethasone decreased wound-induced release of TGF-beta1 and the expression
      of collagen I, fibronectin, and TbetaR-II. These results suggest that ASMC injury
      may play an important role in airway fibrosis mediated by TGF-beta1, which can be
      prevented by the use of corticosteroids.

PMID- 12208094
TI  - Kernicterus: an international perspective.
AB  - Kernicterus occurs in all parts of the world. The risk is increased in countries
      where glucose-6-phosphate dehydrogenase-deficiency is common. In the 1990's more
      case reports of infants who developed kernicterus were published than in the
      previous decades. A combination of reduced concern for jaundice in newborns,
      early discharge with inadequate follow-up and a decreased awareness of the signs
      that may herald serious toxicity may have contributed to the apparent increase in
      the incidence of kernicterus. Although most jaundiced newborns do not need
      aggressive evaluation or treatment, physicians who deal with such infants still
      need to be vigilant. We lack the necessary tools to distinguish infants who may
      be particularly vulnerable to the effects of bilirubin on the brain from those
      who may tolerate high serum bilirubin levels without harm. Therefore it is
      imperative that each infant with significant jaundice be conscientiously
      evaluated and a plan for testing and, if necessary, therapy be formulated.
      Transcutaneous measurement of bilirubin is a simple tool that significantly
      reduces the need for invasive tests. Signs of possible neurotoxicity must never
      be disregarded or neglected. Any jaundiced infant who shows signs of possible
      neurotoxicity should receive intensive phototherapy as an emergency procedure
      while further evaluation continues. Further studies regarding bilirubin toxicity
      and neonatal jaundice are needed, both in the basic science as well as in the
      clinical arena.

PMID- 12208095
TI  - Pharmacological interventions for the treatment of neonatal jaundice.
AB  - In the neonate, hyperbilirubinaemia is usually due to a combination of an
      increased bilirubin load and decreased bilirubin elimination. Despite an
      understanding of the enzymatic pathways leading to bilirubin production and
      elimination, very few pharmacological interventions to prevent
      hyperbilirubinaemia are utilized and the mainstay of treatment remains
      phototherapy. Previously studied pharmacological agents such as D-penicillamine,
      phenobarbital and clofibrate may yet prove useful. Recent clinical trials using
      metalloporphyrins to inhibit heme catabolism and bilirubin production provides a
      novel pharmacological intervention for the treatment of neonatal jaundice. The
      safety and efficacy of these therapies will need to be confirmed prior to
      widespread use.

PMID- 12208097
TI  - Non-invasive bilirubinometry in neonatal jaundice.
AB  - This chapter will focus on techniques that have been developed to measure
      transcutaneous bilirubin (TcB). The first electronic TcB device proved to be
      useful when used as a screening method for identifying newborns who needed a
      serum bilirubin determination. Newer TcB devices can be used not only as
      screening tools but also as reliable substitutes for serum bilirubin
      measurements. The Chromatics Colormate III is still based on the colour of the
      skin, estimating serum bilirubin from skin-reflectance (skin colour) whereas the
      BiliCheck measures transcutaneous bilirubin by utilizing the entire spectrum of
      visible light (380 to 760 nm) reflected by the skin.

PMID- 12208096
TI  - Glucose-6-phosphate dehydrogenase deficiency: a potential source of severe
      neonatal hyperbilirubinaemia and kernicterus.
AB  - Glucose-6-phosphate dehydrogenase (G-6-PD) deficiency is a commonly occurring
      enzyme defect that can lead to severe neonatal hyperbilirubinaemia and
      kernicterus. Both increased haemolysis, sometimes due to an identifiable chemical
      trigger or to infection, and diminished bilirubin conjugation, the result of an
      interaction between G-6-PD deficiency and Gilbert's syndrome, contribute to the
      pathogenesis of the jaundice. Phototherapy is the mainstay of treatment, with
      exchange transfusion held in reserve for those neonates who do not respond to
      phototherapy. Pharmacological agents such as Sn-mesoporphyrins, which prevent
      bilirubin production by inhibiting the enzyme heme oxygenase, can limit
      hyperbilirubinaemia and possibly prevent the need for exchange transfusion.
      Predischarge serum total bilirubin screening is useful in predicting which
      neonates are at high risk for developing hyperbilirubinaemia. Migration patterns
      make G-6-PD deficiency a condition which may nowadays be encountered in virtually
      any corner of the globe and a high degree of physician awareness is essential.

PMID- 12208098
TI  - Breast-feeding, neonatal jaundice and kernicterus.
AB  - Despite the many advantages of breast-feeding, there is ample documentation of
      the strong association between breast-feeding and an increase in the risk of
      neonatal hyperbilirubinaemia. Breast-fed infants have higher bilirubin levels
      than formula-fed infants. Suggested mechanisms for these findings include poor
      fluid and caloric intake, inhibition of hepatic excretion of bilirubin, and
      intestinal absorption of bilirubin (enterohepatic circulation). On rare
      occasions, breast-fed infants without evidence of haemolysis have developed
      extreme hyperbilirubinaemia and kernicterus. Because almost all of the cases of
      kernicterus reported in the last 15 years have occurred in fully or partially
      breast-fed newborns, it is important that these infants be followed closely.
      Appropriate support and advice must be provided to the lactating mother so that
      successful breast-feeding can be established and the risk of severe
      hyperbilirubinaemia reduced.

PMID- 12208099
TI  - Understanding neonatal hyperbilirubinaemia in the era of genomics.
AB  - The genomics revolution offers novel approaches to scientific investigation.
      Application of genomics technologies including microarray gene chips will provide
      a more complete picture of biological phenomena and help define the genetic
      contribution to disease by monitoring changes in expression across thousands of
      genes in physiological and clinical contexts. We briefly summarize identified
      genetic components that contribute to the genesis of neonatal hyperbilirubinaemia
      with a focus on inborn errors of hepatic bilirubin conjugation and discuss the
      potential use of microarray gene expression profiling technology to enhance our
      understanding of the pathogenesis of hyperbilirubinaemic neuronal cell injury.
      Expanded study using the tools of genomics will shed insights into the genetics
      of newborn jaundice and the pathogenesis of hyperbilirubinaemic encephalopathy.

PMID- 12208100
TI  - Neonatal cholestasis.
AB  - Neonatal cholestasis must always be considered in a newborn who is jaundiced for
      more than 14-21 days and a measurement of the serum total and conjugated
      bilirubin in these infants is mandatory. Conjugated hyperbilirubinaemia, dark
      urine and pale stools are pathognomic of the neonatal hepatitis syndrome which
      should be investigated urgently. The neonatal hepatitis syndrome has many causes
      and should be investigated using a structured protocol. The most important
      condition in the differential diagnosis is biliary atresia and affected infants
      require a Kasai portoenterostomy performed by an experienced surgeon, ideally
      before the infant is 60 days old. A modified evaluation schedule should be used
      for preterm infants who have required neonatal intensive care. Genetic causes of
      the neonatal hepatitis syndrome are increasingly recognized and early diagnosis
      facilitates genetic counselling and, in some situations, specific treatment. The
      management of cholestasis is largely supportive, consisting of aggressive
      nutritional support with particular attention to fat-soluble vitamin status. The
      use of ursodeoxycholic acid is associated with improvement in biochemical
      measures of cholestasis and may improve the natural history of cholestasis in
      some circumstances. Outcome is dependent on aetiology. In idiopathic neonatal
      hepatitis more than 90% make a complete biochemical and d clinical recovery.

PMID- 12208101
TI  - Tenascin and proteoglycans: the role of tenascin and proteoglycans in canine
      tumours.
AB  - Tenascin is a high molecular weight, extracellular matrix glycoprotein, subject
      to complex spatial and temporal patterns of expression during embryogenesis,
      wound healing and neoplastic processes. Proteoglycans are complex macromolecules,
      containing one or more glycosaminoglycans attached to a core protein, which are
      involved in cell-cell and cell-matrix interaction. Altered expression of both
      tenascin and proteoglycans has been found in tumours and expression of these two
      extracellular matrix proteins seems to be modulated in the same way in human and
      canine tumours. The quantitative and qualitative changes in tenascin and
      proteoglycan composition may significantly affect behaviour of tumour cells.
      While tenascin and proteoglycans have many biological functions likely to
      influence tumour development and progression, their exact role in regulation of
      tumour cell-cell interaction, proliferation, invasion and metastasis remains to
      be established. This review focuses on the role of tenascin and proteoglycans in
      neoplasia and recent developments in canine tumours.

PMID- 12208102
TI  - The application of nucleic acid vaccines in veterinary medicine.
AB  - Nucleic acid immunisation entails the delivery of DNA (or RNA) encoding a vaccine
      antigen to the recipient. The DNA is taken up by host cells and transcribed to
      mRNA, from which the vaccine proteins are then translated. The expressed proteins
      are recognised as foreign by the host immune system and elicit an immune
      response, which may have both cell-mediated and humoral components. DNA vaccines
      offer a number of advantages over conventional vaccines, including ease of
      production, stability and cost. They also allow the production of vaccines
      against organisms which are difficult or dangerous to culture in the laboratory.
      This review describes the principles of DNA vaccination and the application of
      DNA vaccines to veterinary species. Although a great deal of developmental work
      is required before the technology can give rise to commercial vaccines in
      domestic animals, there is ongoing research in many fields and it is expected
      that a number of exciting developments will arise in the next decade.

PMID- 12208103
TI  - Rabies: recent developments.
AB  - Rabies remains as one of the most feared zoonotic diseases in the world. All warm
      blooded animals are susceptible to infection by the virus, but the main vectors
      of human infection are dogs and cats. The control of rabies largely depends on
      the prevention of infection of dogs and cats by vaccination in endemic areas and
      the control of their movement, including measures of quarantine and vaccination,
      in rabies-free countries. This paper provides an overview on recent developments
      in rabies, with particular emphasis on the epidemiology, pathogenesis, diagnosis,
      and control.

PMID- 12208104
TI  - Virulence factors of Escherichia coli serotypes associated with avian
      colisepticaemia.
AB  - The current understanding of the pathogenesis of avian pathogenic Escherichia
      coli (APEC) in colisepticaemia is limited. This review discusses putative
      virulence determinants per se, such as a number of surface organelles including
      fimbriae and flagella; together with other factors such as iron sequestering
      mechanisms, which are involved in the survival of E. coli in the host rather than
      initiation of infection. It is concluded that avian colisepticaemia is a multi
      factorial disease and that to date only a limited number of virulence factors of
      APEC have been thoroughly elucidated.

PMID- 12208105
TI  - Experimental induction of pneumonic pasteurellosis in calves by intratracheal
      infection with Pasteurella multocida biotype A:3.
AB  - The study aimed to establish an experimental model to investigate the
      pathogenesis of lung infection by Pasteurella multocida, an important cause of
      bovine respiratory disease. An experimental model is required to assist the
      development of an effective vaccine. Sixteen 8-week-old calves were challenged
      intratracheally with 10(9) or 10(10) colony forming units of P. multocida in
      either 60 or 300 ml saline in a 2 x 2 factorial experiment. All animals became
      dull within 2-6h post-infection (p.i.) and two calves were killed humanely
      because of suspected endotoxic shock. Remaining animals showed increased
      respiratory rates by 15-20 h p.i. and, at 23 h p.i., calves given the high dose,
      high volume challenge showed higher (P < 0.05) rectal temperatures. From 24 to 36
      h p.i., clinical signs decreased in a majority of animals. Plasma haptoglobin
      concentrations increased (P < 0.05) in calves given the high volume challenge
      irrespective of the number of bacteria. At post-mortem examination (4d p.i.),
      lung lesions, mainly in the apical lobes, were found in all calves.
      Histopathological examination showed areas of purulent pneumonia with a tendency
      to abscessation and inflamed interlobular septa characterised by accumulation of
      neutrophils and oedema. The clinical and pathological responses described were
      typical of bovine pneumonic pasteurellosis.

PMID- 12208106
TI  - Proliferation activity in oral and cutaneous canine melanocytic tumours:
      correlation with histological parameters, location, and clinical behaviour.
AB  - A total of 62 canine melanocytic tumours (10 melanocytomas and 52 primary
      malignant melanomas) were investigated to compare the accuracy of prognosis
      provided by MIB-1 proliferation index (MIB-1-PI) with classical histological
      criteria and location. MIB-1-PI was assessed by means of quantitative image
      analysis of sections immunostained with MIB-1 monoclonal antibody. Tumour
      location, histological cell type, stromal or lymphatic vessel invasion, maximum
      tumour thickness, and presence of inflammation or necrosis were recorded for each
      case. Thirty-eight dogs were submitted to a 1-year follow-up and the clinical
      outcome of the disease determined. MIB-1-PI in melanocytomas differed
      significantly from that detected in primary malignant melanomas (P=0.0001). A
      significant difference in MIB-1-PI was revealed between oral and cutaneous
      malignant melanomas (P=0.015), and between presence and absence of lymphatic
      vessel invasion (P=0.05). MIB-1-PI was not correlated with the other parameters.
      In univariate analysis, only tumour location (oral vs cutaneous), presence of
      lymphatic vessel invasion, and MIB-1-PI were associated with decreased overall
      survival (P=0.0001,P=0.0144, and P=0.0489, respectively). In conclusion, the
      results of our study confirm that the assessment of the MIB-1-PI may be of
      additional prognostic value for dogs with primary malignant melanomas.

PMID- 12208107
TI  - Multiparametric survival analysis of histological stage and proliferative
      activity in feline mammary carcinomas.
AB  - Mammary tumours are among the most frequent malignant neoplasms in the cat and
      determination of prognosis on histological grounds alone can be unsatisfactory
      because it does not always correspond to the clinical behaviour of the neoplastic
      disease. The aim of this two-year post-mastectomy survival study is to relate the
      histological stage or invasiveness (the most commonly used histological parameter
      to grade malignancy) to several parameters assessing the proliferative activity
      mitotic index, MIB1 index, and AgNOR index. Invasiveness was graded as local and
      vascular invasion whilst values of the parameters expressing proliferative
      activity, all quantified by image analysis, have been classified into low and
      high proliferative activity groups according to their median values, (0.719 for
      mitotic index, 12.11 for MIB1 index, and 3.19 for AgNOR index). For each group,
      mean survival (months+/-SD) was calculated. Histological stage (local invasion
      21.83+/-7.83 months, blood vessels and/or lymphatics invasion 13.38+/
      8.99,P<0.01), mitotic index (low 22.43+/-88.78, high 12.37+/-7.49,P<0.001), and
      AgNOR index (low 21.86+/-10.68, high 13.82+/-7.11,P<0.05) revealed a significant
      association with survival in univariate analysis and had an independent
      prognostic value in multiparametric survival test (P<0.001).

PMID- 12208108
TI  - Effects of local anaesthesia or local anaesthesia plus a non-steroidal anti
      inflammatory drug on the acute cortisol response of calves to five different
      methods of castration.
AB  - The cortisol response of calves to different methods of castration (ring, band,
      surgical, clamp) with or without local anaesthetic, or local anaesthetic plus a
      non-steroidal anti-inflammatory drug were recorded. All methods of castration
      caused a significant cortisol response and by inference pain and distress. Band
      castration caused a greater cortisol response than ring castration but the
      responses were eliminated by local anaesthetic. The cortisol response to surgical
      castration, by traction on the spermatic cords or by cutting across them with an
      emasculator, was not diminished by local anaesthetic but when ketoprofen was
      given with local anaesthetic the cortisol response was eliminated. Local
      anaesthetic did reduce the behavioural response to cutting the scrotum and
      handling the testes. Clamp castration caused the smallest cortisol response which
      was reduced or eliminated by local anaesthetic or local anesthetic plus
      ketoprofen respectively, but this method of castration was not always successful.

PMID- 12208109
TI  - The accuracy of the i-STAT portable analyser for measuring blood gases and pH in
      whole-blood samples from dogs.
AB  - To assess the suitability of the i-STAT portable analyser for use by non
      laboratory personnel, we measured blood gases and pH in venous blood samples from
      100 dogs. Deming's regression and bias plots were used to compare i-STAT results
      with those obtained by laboratory professionals using two different
      autocalibrated benchtop analysers. Overall accuracy of the portable analyser
      proved excellent for pH, pO(2), and pCO(2) (r=0.978, 0.968 and 0.997,
      respectively), with Deming's regression slopes close to 1.00 (0.96, 0.97 and 1.08
      for pH, pO(2), and pCO(2), respectively) and intercepts close to zero (0.28, 0.47
      kPa and 0.46 kPa for pH, pO(2), and pCO(2), respectively). The accuracy of the i
      STAT was also satisfactory for calculated parameters: bicarbonates, total CO(2),
      base excess and oxygen saturation. Our findings show this portable analyser to be
      a valid substitute for expensive benchtop analysers in situations requiring
      mobility, or when small numbers of tests are to be performed by users not
      specialized in laboratory techniques.

PMID- 12208110
TI  - Localisation of CD25+ cells and MHCII+ cells in lymph nodes draining
      Mycobacterium avium subsp. paratuberculosis vaccination granuloma and the
      presence of a systemic immune response.
AB  - Vaccination of goat kids against paratuberculosis protects against lesions and
      clinical disease. The systemic cellular response was studied in goat kids 3-9
      weeks after vaccination. Peripheral blood cells showed increased interferon-gamma
      production and expression of interleukin-2 receptor (CD25) after stimulation with
      Mycobacterium avium subsp. paratuberculosis antigens. The lymph node draining the
      vaccination granuloma was studied three weeks after vaccination in a parallel
      group of goat kids. In deep cortex, MHCII+ cells were observed surrounded by CD4+
      T-cells, while follicular hypertrophy and hyperplasia were prominent in the
      subcapsular region and along connective tissue trabecula. Comparison of the local
      and systemic immune responses revealed an inverse relationship between CD25+ T
      cells in the lymph node deep cortex and cells in peripheral blood that up
      regulate CD25 upon in vitro stimulation, suggesting that activated and regulatory
      T-cells in the local lymph node influence the level of circulating antigen
      specific T-cells following vaccination against paratuberculosis in goats.

PMID- 12208111
TI  - Osteological features in pure-bred dogs predisposing to thoracic or lumbar spinal
      cord compression.
AB  - Consistent with those vertebral sites most commonly clinically affected by spinal
      cord compression, body size normalised midsagittal diameters of the caudal
      vertebral foramen limits T10-T12 were significantly (P<0.05) lower in Dachshunds
      relative to other breeds. Minimal midsagittal diameters in Yorkshire Terriers and
      Maltese were noted at T11cd/12cr. However, these diameters were always larger
      (P<0.05) in small breeds compared to those in Dachshunds and large breeds
      suggesting that the small breeds investigated are at lower risk of developing
      clinical signs if a compressive disease occurs at that site. In large breeds,
      minimal values were present at L1cd/L2cr and in agreement with clinical findings
      correlate with those spinal sites most susceptible to spinal cord compression in
      nonchondrodystrophic large breeds. Caudal displacement of the lumbosacral
      enlargement of the spinal cord relative to the position previously noted in large
      breeds was confirmed for the Dachshunds and 50% of small breeds. However, caudal
      displacement was also noticed in the German Shepherd dogs.

PMID- 12208112
TI  - Gamma herpesvirus carrier status of captive artiodactyls.
AB  - Between 1998 and 2000, 103 individuals of 19 species of the order Artiodactyla at
      Whipsnade Wild Animal Park were tested for evidence of infection with gamma
      herpesviruses in order to distinguish between species which are susceptible to
      malignant catarrhal fever (MCF), caused by alcelaphine herpesvirus-1 (AlHV-1) of
      wildebeest (Connochaetes sp.) or ovine herpesvirus-2 (OvHV-2) of domestic sheep,
      and species which carry related viruses sub-clinically. Gamma herpesvirus DNA was
      detected in the known, or suspected, carrier species: roan antelope (Hippotragus
      equinus), scimitar-horned oryx (Oryx dammah), gemsbok (Oryx gazella), musk ox
      (Ovibos muschatus) and mouflon (Ovis musimon). In six other species: lowland anoa
      (Bubalus depressicornis) yak (Bos grunniens), sitatunga (Tragelaphus spekei),
      greater kudu (Tragelaphus strepsiceros), waterbuck (Kobus ellipsiprymnus) and
      Nile lechwe (Kobus megaceros), DNA was present in some newborn calves and over
      30% of adults, strongly suggesting a carrier state. In contrast five Pere David's
      deer (Elaphurus davidianus) and two swamp deer (Cervus duvauceli) died of MCF
      during the study. A virus isolated from scimitar-horned oryx calves produced
      cytopathic effects in scimitar-horned oryx kidney cell-culture and caused MCF in
      a rabbit.

PMID- 12208113
TI  - Evaluation of biochemical characters of broiler chickens during dietary aflatoxin
      (50 and 100 ppb) and clinoptilolite exposure.
AB  - Aflatoxin (AF) and clinoptilolite (CLI, a natural zeolite) were added to broiler
      food and some biochemical values and enzyme activities were evaluated. The
      experimental design consisted of six dietary treatments. (1) CONTROL: basal diet;
      (2) CLI: basal diet plus 15 g clinoptilolite kg(-1) diet; (3) 50 ppb AF: basal
      diet plus 50 microg total aflatoxin (AF; the composition given below) kg(-1)
      diet; (4) 50 ppb AF+CLI: basal diet plus 50 microg AF plus 15 g CLI kg(-1) diet;
      (5) 100 ppb AF: basal diet plus 100 microg AF kg(-1) diet; (6) 100 ppb AF+CLI:
      basal diet plus 100 microg AF plus 15 g CLI kg(-1) diet. A commercially available
      CLI was provided from the west region of Turkey and its chemical formula is
      "KNa(2)Ca(2)(Si(29)AL(7))O.7(2).32H(2)O". For this a total of 576 1-day-old Ross
      broiler chicks were housed in six treatment groups from days 1 to 42. AF
      treatment significantly increased the serum Na levels and the aspartate-amino
      transferase (ASAT) and alanine-amino-transferase (ALAT) enzyme activities, while
      total protein, albumin, total cholesterol uric acid, and K levels were not
      significantly different between groups. These results suggest that these low AF
      levels in food did not change the serum biochemistry but significantly affected
      the enzyme activities in broilers.

PMID- 12208114
TI  - Nonsteroidal anti-inflammatory drugs and inflammatory bowel disease: current
      perspectives.
AB  - Mechanisms underlying the gastric toxicity of nonsteroidal anti-inflammatory
      drugs (NSAIDs) have been extensively investigated, whereas those leading to
      intestinal damage are not completely understood. Several hypotheses have been put
      forward on the pathophysiology of intestinal damage by NSAIDs: enhanced
      intestinal permeability, inhibition of cyclooxygenase (COX), enterohepatic
      recirculation, and formation of adducts. The effects of COX-2 selective
      inhibitors, which appear to have better gastric tolerability when compared to
      nonselective NSAIDs, on normal and inflamed intestinal mucosa (as in Crohn's
      disease or ulcerative colitis) are still largely unexplored. If COX-2 inhibition
      plays a key role in suppressing the inflammatory process, recent evidence
      suggests that COX-2 products are involved in maintaining the integrity of
      intestinal mucosa, in the healing of gastrointestinal ulcers and in the
      modulation of inflammatory bowel disease (IBD). Animal models of intestinal
      inflammation have so far yielded conflicting results on the effects of COX-2
      selective inhibitors on the intestinal mucosa. It is now clear that NSAIDs do not
      act through cyclooxygenase inhibition, but also have different targets such as
      nuclear factor-kappaB and/or peroxisome proliferator-activated receptors gamma.
      The peculiar pharmacological profile of each compound may help to explain the
      different impact of each NSAID on the inflammatory process and on IBD. Notably,
      the salicylic acid derivative 5-ASA is widely used in the treatment of IBD and is
      believed to act through nuclear factor-kappaB inhibition. Although the use of COX
      2 selective inhibitors remains contraindicated in patients with IBD, studying
      their effects on intestinal mucosa may offer new insights into their subcellulars
      mechanisms of action and open new avenues for the development of novel therapies
      for IBD.

PMID- 12208115
TI  - Etidronate influences growth and phenotype of rat vascular smooth muscle cells.
AB  - Bisphosphonates have been reported to exhibit antiarteriosclerotic and
      anticalcification effects. We investigated the effect of a bisphosphonate,
      etidronate, on growth and phenotype of vascular smooth muscle cells (VSMC) from
      spontaneously hypertensive rats (SHR). Etidronate (10 microM) significantly
      decreased DNA synthesis evaluated by [3H]thymidine incorporation in VSMC cultured
      without serum, and 1 microM etidronate significantly inhibited DNA synthesis in
      the presence of 10% calf serum. Etidronate (10 microM) significantly inhibited
      VSMC proliferation after 72h incubation. Etidronate (100 microM) significantly
      increased the expression of SM22alpha mRNA and protein in VSMC, while 10 microM
      etidronate significantly decreased the expression of matrix Gla mRNA. These
      findings indicate that etidronate inhibits the exaggerated growth of VSMC from
      SHR, while altering their phenotype from synthetic to contractile one. These
      effects of etidronate may account for its antiarteriosclerotic action.

PMID- 12208116
TI  - Effects of vasoconstrictors used in local anesthesia upon isolated rat heart.
AB  - Some reports have demonstrated that the vasoconstrictor effect of catecholamines
      may be amplified by felypressin. Thus, the association of felypressin and
      epinephrine with local anesthetics may be indicated to achieve more effective
      vasoconstrictor actions with fewer collateral effects from both the anesthetic
      and the vasoconstrictor. This study aimed to characterize the effects of
      felypressin and associations of felypressin and epinephrine upon the contraction
      force and the cardiac rate of the isolated rat heart (n=20) perfused by
      Langendorff's method. The following solutions were utilized: epinephrine,
      4.5nmol; felypressin at doses of 0.5, 1.6 and 5.5IU and associations of
      felypressin at the same doses with 4.5nmol epinephrine. Contraction force and
      cardiac rate were recorded at 15, 30, 60 and 120s after the administration of
      each solution, and before the administration, a control measurement (time 0) was
      taken. Felypressin at a dose of 0.5IU did not have any effect upon the heart, but
      the doses of 1.6 and 5.5IU decreases the cardiac rate and the contraction force,
      respectively. Epinephrine and all of the felypressin and epinephrine associations
      produced increases in these parameters. The association of 0.5IU felypressin and
      4.5nmol epinephrine promoted a similar effect to that of epinephrine (4.5nmol)
      alone up to 120s. The association of 1.6IU felypressin and 4.5nmol epinephrine
      increases the contraction force up to 60s. After the administration of the
      association of 5.5IU felypressin and 4.5nmol epinephrine this increase was
      observed up to just 30s. The cardiac rate values obtained after the
      administration of the associations of 1.6 and 5.5IU felypressin with 4.5nmol
      epinephrine were lower than those seen after the use of 4.5nmol epinephrine
      alone. In this study it was observed that the association of felypressin with
      epinephrine decreased the effects of epinephrine which increases the cardiac rate
      and the contraction force in the isolated rat heart.

PMID- 12208117
TI  - Sodium channel blocking and antiarrhythmic actions of the novel arylpiperazine
      rsd992.
AB  - Bolus doses (4-128 micromolkg(-1)) and infusions (2-32 micromolkg(-1)min(-1)) of
      the novel arylpiperazine drug RSD992 produced bradycardia in rats and guinea pigs
      but had minimal effect on ECG variables. RSD992 (2-32 micromolkg(-1)min(-1))
      increased threshold current (I(T)) for induction of extra-systoles and induction
      of sustained ventricular fibrillation (VF(T)) and also increased the effective
      refractory period (ERP) and decreased the maximum following frequency (MFF) in
      rat and guinea pig hearts. RSD992 (32-512 microM) significantly increased PR and
      QRS intervals in isolated rat hearts subjected to conditions that mimic ischaemia
      (pH 6.4, K(+) 11mM) but not in isolated hearts under normal perfusion conditions
      (pH 7.4, K(+) 3mM). RSD992 (0.1-3.0mM) reduced peak sodium current in rat cardiac
      (rNa(v)1.5) sodium channels more potently than neuronal (rNa(v)1.2a) sodium
      channels expressed in Xenopus oocytes. The voltage-dependence of sodium channel
      activation was unaffected whereas inactivation was shifted in a hyperpolarized
      direction thus suggesting RSD992 may preferentially interact with the inactive
      state of the sodium channel, a state usually associated with myocardial cell
      depolarization in ischaemic myocardium. RSD992 (2-24 micromolkg(-1)min(-1))
      decreased the incidence of ventricular arrhythmias and mortality in rats subject
      to coronary artery ligation. RSD992 exhibits frequency- and ischaemia-selective
      actions on myocardial sodium currents and antiarrhythmic actions in ischaemic rat
      myocardium.

PMID- 12208118
TI  - Effects of subacute lead acetate administration on nitric oxide and
      cyclooxygenase pathways in rat isolated aortic ring.
AB  - Low level exposure to lead increases blood pressure in human and rats. In this
      study, we investigated the contribution of the nitric oxide (NO) and
      cyclooxygenase pathways of aortic rings of 28-day lead-treated and control rats,
      to the responsiveness to phenylephrine and acetylcholine. There were no
      differences in phenylephrine contractions between the two groups. N(omega)-nitro
      L-Arginine-methyl ester (L-NAME), a NO synthase inhibitor, caused attenuation in
      contraction response to phenylephrine in the aortic rings of the lead-treated
      rats, while endothelium-denudation caused attenuation in those of controls. This
      may be due to either endothelium-derived vasoconstrictor(s) (such as reactive
      oxygen species or endothelins) or a source of NO in smooth muscle cells. There is
      a left-shift in acetylcholine relaxation response. Indomethacin incubation caused
      a left-shift in relaxation response to acetylcholine in controls but without any
      effect on lead-treated ones. Indomethacin incubation caused attenuation in
      contraction to phenylephrine in both groups. The relaxation response to sodium
      nitroprusside is not different between the two groups, suggesting that smooth
      muscle relaxation component is intact. However, the relaxation response to
      glyceryl trinitrate is impaired in aortic rings of lead-treated rats. It can be
      concluded that NO and cyclooxygenase pathways are altered in aortic rings of lead
      treated rats, with possible involvement of endothelium-derived vasoconstrictors.

PMID- 12208119
TI  - Bis-1,7-(2-hydroxyphenyl)-hepta-1,6-diene-3,5-dione (a curcumin analog)
      ameliorates DMH-induced hepatic oxidative stress during colon carcinogenesis.
AB  - The protective effect of a curcumin analog [bis-1,7-(2-hydroxyphenyl)-hepta-1,6
      diene-3,5-dione] was investigated on hepatic lipid peroxidation (LPO) and
      antioxidant status during 1,2-dimethylhydrazine-induced colon carcinogenesis in
      male Wistar rats. The effects were compared with that of curcumin, a known
      antioxidant and anticarcinogen. Colon cancer was induced by sub-cutaneous
      injection of DMH at a dosage of 20mg/kg body weight (15 doses, at 1-week
      intervals). DMH administered rats developed gross tumours in the colon. Enhanced
      lipid peroxidation in the liver of colon tumour bearing rats was accompanied by a
      significant decrease in the activities of glutathione peroxidase (GPx),
      glutathione S-transferase (GST), superoxide dismutase (SOD) and catalase (CAT).
      Intragastric administration of curcumin (80mg/kg body weight) and curcumin analog
      (80mg/kg body weight) to DMH-injected rats significantly reduced the number and
      size of tumour in the colon, lowered lipid peroxidation and enhanced the
      activities of GPx, GST, SOD and CAT in the liver. We speculate that the curcumin
      analog used in the present study exerts chemoprevention against cancer
      development at extrahepatic sites by modulating hepatic biotransformation enzymes
      and antioxidant status. The effect is comparable with that of curcumin. This
      shows that the hydroxyl group in the aromatic ring is responsible for the
      protective effect rather than the methoxy group.

PMID- 12208120
TI  - Influence of mianserin on some central effects of ethanol.
AB  - The interaction of mianserin with ethanol in central nervous system (CNS) was
      investigated. Mianserin was administered at a single dose of 5 or 20 mgkg(-1)
      i.p. or as daily injections in a dose of 2.5 mgkg(-1) given for 14 days. The
      influence of mianserin on acute ethanol toxicity (LD(50)), on ED(50) of ethanol
      in rota-rod test, on the duration of ethanol sleeping time as well as on
      spontaneous locomotor activity and ethanol-induced hypothermia was investigated.
      Moreover, the influence of mianserin administered in a dose of 10 mgkg(-1) i.p.
      on post-ethanol changes in the bioelectric brain activity (EEG) recordings in
      rabbits was also investigated. The electrodes were implanted into midbrain
      reticular formation (MRF), dorsal hippocampus (Hp) and frontal cortex (C).
      Mianserin administered as a single dose of 5 mgkg(-1) was found to decrease
      LD(50) of ethanol and its ED(50) in rota-rod test. Mianserin administered as a
      single dose of 5 or 20 mgkg(-1) prolongs ethanol sleeping time in mice but given
      daily for 14 days has no influence on this time. Mianserin-induced hypothermia
      was observed after administration of single dose as well as increase of ethanol
      induced hypothermia after administration of higher dose (20 mgkg(-1)). Mianserin
      administered daily for 14 days had no influence on post-ethanol changes in body
      temperature. Single dose of mianserin 20 mgkg(-1) decreases locomotor activity in
      mice while repeated administration has no influence on locomotor activity. In
      contrast, both single dose and repeated administration of mianserin prevents
      increased locomotor activity of animals observed after ethanol (2.5 mgkg(-1)).
      Mianserin administered to rabbits (10 mgkg(-1)) induces increase of share of low
      frequency 0.5-4 cps and decrease of share of frequencies 4-7 and 7-10 cps in EEG
      recordings from MRF and Hp. The recordings from frontal cortex show increase of
      share of frequencies 10-13 cps. Ethanol increases the share of low frequencies in
      EEG recordings and decreases the share of fast frequencies. Mianserin increases
      its influence on fast frequencies.

PMID- 12208121
TI  - Acute swimming stress induces changes in noradrenergic mechanisms in order to
      maintain the response pattern of the rat vas deferens to norepinephrine.
AB  - This study investigated mechanisms involved in the maintenance of the functional
      response pattern of the postjunctional alpha(1)-adrenoceptor in vas deferens
      isolated from rats submitted to acute swimming stress. The plasma corticosterone
      levels increased approximately three times after the swimming stress in the
      nontreated rats as well as after swimming stress in the rats pretreated with
      desipramine (DMI), yohimbine (YO), or DMI with YO. No alteration was detected in
      the sensitivity to norepinephrine (NE) in the vasa deferentia from the stressed
      rats or stressed rats treated with DMI or DMI with YO, in relation to their
      respective control. However, when the vasa deferentia were previously incubated
      with DMI, a reduction in sensitivity to NE in organs from stressed rats was
      observed. Vasa deferentia excised from rats pretreated with YO before the
      swimming stress showed an increase in postjunctional alpha(1)-response that was
      abolished by prazosin (PZ). Thus, the neuronal uptake, the prejunctional alpha(2)
      adrenoceptors (mediating prejunctional inhibition), the occupancy and functional
      response of the postjunctional alpha(1)-adrenoceptors, and the emotional stress
      component were very important for the determination of the noradrenergic response
      pattern in vas deferens from rats submitted to acute swimming stress.

PMID- 12208122
TI  - Monoaminergic and cholinergic stimulation of masculine sexual behavior in
      neonatally demasculinized male rats.
AB  - Sexual behavior during adulthood largely depends upon hormonal events that take
      place around birth. Administration of the antiestrogen Tamoxifen (Tx) to males
      immediately after birth induces a marked decrease of masculine sexual behavior
      during adulthood. On the other hand, it is well known that masculine sexual
      behavior can be stimulated by the administration of drugs acting specifically on
      the monoaminergic or the cholinergic systems. This study was performed to analyze
      if masculine sexual behavior can be pharmacologically stimulated in adult male
      rats neonatally demasculinized by the administration of Tx. Neonatal
      administration of Tx induced clear impairments of masculine sexual behavior
      during adulthood. Administration of oxotremorine (OXO), 8-OH-DPAT (8-hydroxy-2(di
      n-propylaminotetraline)), yohimbine (YH), and apomorphine (APO), drugs that
      normally elicit a stimulation of masculine sexual behavior were unable to fully
      restore it in demasculinized males. Only slight improvements of some behavioral
      parameters were observed with 8-OH-DPAT and YH. OXO seems to induce a worsening
      of sexual behavior impairments. Results obtained with APO were not significantly
      different from saline controls. Data suggest that neonatal treatment with Tx
      induces permanent impairments of the neural circuitry regulating masculine sexual
      behavior not only limited to morphological changes but also functional
      alterations of the neurotransmitter systems.

PMID- 12208123
TI  - Poly(Adp-ribose) synthetase inhibition prevents lipopolysaccharide-induced
      peroxynitrite mediated damage in diaphragm.
AB  - Although the precise mechanism by which sepsis causes impairment of respiratory
      muscle contractility has not been fully elucidated, oxygen-derived free radicals
      are thought to play an important role. In our experimental study, the effects of
      poly(ADP-ribose) synthetase (PARS) inhibition on the diaphragmatic Ca(2+)-ATPase,
      malondialdehyde (MDA), and 3-nitrotyrosine (3-NT) levels and additionally
      histopathology of the diaphragm in lipopolysaccharide (LPS)-induced endotoxemia
      are investigated.Thirty-two male Wistar rats, weighing between 180-200 g were
      randomly divided into four groups. The first group (control; n=8) received saline
      solution and the second (LPS group; n=8) 10 mgkg(-1) LPS i.p. 3-Aminobenzamide (3
      AB) as a PARS inhibitor; was given to the third group (C+3-AB, n=8) 20 min before
      administration of saline solution while the fourth group (LPS+3-AB, n=8) received
      3-AB 20 min before LPS injection. Six hours later, under ketamin/xylasine
      anesthesia diapraghmatic specimens were obtained and the rats were decapitated.
      Diaphragmatic specimens were divided into four parts, three for biochemical
      analyses and one for histopathologic assessment. In the LPS group, tissue Ca(2+)
      ATPase levels were found to be decreased and tissue MDA and 3-NT levels were
      found to be increased (P<0.05). In the LPS+3-AB group, 3-AB pretreatment
      inhibited the increase in MDA and 3-NT levels and Ca(2+)-ATPase activity remained
      similar to those in the control group (P<0.05). Histopathologic examination of
      diaphragm showed edema between muscle fibers only in LPS group. PARS inhibition
      with 3-AB prevented not only lipid peroxidation but also the decrease of Ca(2+)
      ATPase activity in endotoxemia. These results highlights the importance of nitric
      oxide (NO)-peroxynitrite (ONOO(-))-PARS pathway in preventing free radical
      mediated injury. PARS inhibitors should further be investigated as a new
      thearapetic alternative in sepsis treatment.

PMID- 12208124
TI  - Protective effect of omeprazole against acute gastric mucosal lesions induced by
      compound 48/80, a mast cell degranulator, in rats.
AB  - Omeprazole, a proton pump inhibitor is known to function not only as a proton
      pump inhibitor but also as an anti-inflammatory agent, an antioxidant or a
      stimulator of gastric mucus secretion. We have shown that the pathogenesis of
      acute gastric mucosal lesions induced by compound 48/80, a mast cell
      degranulator, in rats involves neutrophil infiltration, lipid peroxidation, and
      mucin depletion, but not acid secretion, in the gastric mucosal tissue.
      Therefore, we examined whether omeprazole protects against acute gastric mucosal
      lesions induced by compound 48/80 in rats. Rats were injected with omeprazole (10
      or 50 mgkg(-1), i.p.) at 0.5h before injection of compound 48/80 (0.75 mgkg(-1),
      i.p.). Omeprazole prevented gastric mucosal lesion development at 0.5 and 3h
      after compound 48/80 injection. Omeprazole attenuated decreased nonprotein
      sulfhydryl content and increased myeloperoxidase and xanthine oxidase (XO)
      activities and lipid peroxide (LPO) content in the gastric mucosa at 0.5h after
      compound 48/80 injection and increased myeloperoxidase and XO activities and LPO
      content, but not decreased hexosamine and adherent mucus contents, in the gastric
      mucosa at 3h. These results indicate that omeprazole protects against compound
      48/80-induced acute gastric mucosal lesions in rats possibly through its anti
      inflammatory and antioxidant actions.

PMID- 12208125
TI  - Increased expression of aquaporin water channels in hypothyroid rat kidney.
AB  - The present study was aimed to determine the molecular mechanisms underlying the
      water retention associated with hypothyroidism. Male Sprague-Dawley rats (200
      220g) were experimentally induced of hypothyroidism by treatment with methimazole
      in drinking water (0.04%) for 8 weeks. In the experimental group, serum
      concentrations of thyroxine and triiodothyronine were significantly decreased.
      The expression of aquaporin 2 (AQP2) was significantly increased in the cortex,
      outer medulla, and inner medulla of the kidney. The expression of AQP1 as well as
      that of AQP3 was significantly increased in the cortex, though not in the
      medulla. The adenylyl cyclase activity provoked by arginine vasopressin (AVP),
      sodium fluoride, or forskolin was blunted in the hypothyroid kidney, while plasma
      levels of AVP were not significantly changed. The increased expression of AQP1-3
      channels may in part account for the water retention in hypothyroidism.

PMID- 12208126
TI  - Prognostic factors for the clinical effectiveness of fluconazole in the treatment
      of oral candidiasis in HIV-1-infected individuals.
AB  - OBJECTIVE: To identify prognostic factors for the clinical effectiveness of
      fluconazole in HIV-1-infected patients with oropharyngeal candidiasis. DESIGN AND
      SETTING: The study was designed as a prospective, open label, non-comparative,
      dose escalating, single centre trial. PATIENTS AND METHODS: Thirty-four HIV-1
      infected patients with oropharyngeal Candida infection were treated with 50 or
      100mg fluconazoleday(-1), depending on the clinical manifestation (erythematous
      or pseudomembranous). The dose was doubled weekly until clinical cure. The
      predictive value of potential prognostic factors for the duration of treatment
      and cumulative fluconazole dose until cure was studied: exposure to fluconazole,
      previous use of fluconazole, the use of antiretroviral drugs, the CD4(+) cell
      count, erythematous or pseudomembranous appearance, the minimum inhibitory
      concentration (MIC) for fluconazole of the isolated Candida strain, and
      xerostomia. RESULTS: Twenty-eight patients (with 30 episodes of oropharyngeal
      candidiasis) were evaluated. Twenty-five episodes were cured within 1-week of
      treatment, the remaining five episodes were cured within 2 weeks. No predictive
      value for any of the studied factors on the duration of fluconazole treatment or
      the cumulative fluconazole dose until cure was demonstrated. CONCLUSION: Because
      of the high susceptibility to fluconazole and the positive clinical outcome, the
      variation in outcome measurements was too modest to establish a significant
      relationship between any of the investigated potentially prognostic factors and
      the cumulative fluconazole dose and the duration of treatment to reach cure. On
      the other hand it can be concluded, that fluconazole is very effective in
      patients with advanced HIV infection and low CD4(+) cell counts, even if they are
      not using antiretroviral agents.

PMID- 12208127
TI  - Improved tonsillar disposition of azithromycin following a 3-day oral treatment
      with 20 mg kg(-1) in paediatric patients.
AB  - The present study was performed in order to compare azithromycin concentrations
      in tonsils of paediatric patients treated with different dose regimens of this
      antibiotic. Sixty-four children, scheduled to undergo surgical removal of
      tonsils, were treated with azithromycin 10 or 20 mgkg(-1) daily as oral
      suspension for 3 days. Samples of blood and tonsil were collected during surgery
      at days 0.5, 2.5, 4.5, 6.5 or 8.5 after the last dose. Azithromycin
      concentrations were measured by reversed phase high-performance liquid
      chromatography. In patients treated with 10 mgkg(-1), the highest concentrations
      of azithromycin were detected in plasma and tonsils at day 0.5 and 2.5,
      respectively. Consistent drug levels could be measured in tonsils up to 8.5 days.
      After administration of 20 mgkg(-1), azithromycin tonsillar concentrations were
      higher than those obtained with 10 mgkg(-1) up to day 6.5, whereas plasma levels
      did not differ significantly. The present results indicate that an improved
      tonsillar distribution of azithromycin can be achieved when this antibiotic is
      administered for 3 days at doses higher than 10 mgkg(-1) daily. These findings
      give pharmacokinetic support to the suggestion that increments of azithromycin
      dosing might ensure enhanced therapeutic levels at infective sites of the upper
      respiratory tract.

PMID- 12208129
TI  - The rise and fall and (urgently needed) rebirth of metabolic medicine. Donough
      O'Brien Presidential Address Society for Inherited Metabolic Disorders, Asilomar,
      CA, 5 March 2002.

PMID- 12208130
TI  - The phenylketonuria mouse model: a meeting review.

PMID- 12208131
TI  - Glucosylsphingosine accumulation in tissues from patients with Gaucher disease:
      correlation with phenotype and genotype.
AB  - Gaucher disease, the inherited deficiency of lysosomal glucocerebrosidase,
      presents with a wide spectrum of clinical manifestations including neuronopathic
      and non-neuronopathic forms. While the lipid glucosylceramide is stored in both
      patients with Gaucher disease and in a null allele mouse model of Gaucher
      disease, elevated levels of a second potentially toxic substrate,
      glucosylsphingosine, are also found. Using high performance liquid
      chromatography, glucosylsphingosine levels were measured in tissues from patients
      with type 1, 2, and 3 Gaucher disease. Glucosylsphingosine was measured in 16
      spleen samples (8 type 1; 4 type 2; and 4, type 3) and levels ranged from 54 to
      728 ng/mg protein in the patients with type 1 disease, 133 to 1200 ng/mg protein
      in the patients with type 2, and 109 to 1298 ng/mg protein in the type 3 samples.
      The levels of splenic glucosylsphingosine bore no relation to the type of Gaucher
      disease, the age of the patient, the genotype, nor the clinical course. In the
      same patients, hepatic glucosylsphingosine levels were lower than in spleen.
      Glucosylsphingosine was also measured in brains from 13 patients (1 type 1; 8
      type 2; and 4 type 3). While the glucosylsphingosine level in the brain from the
      type 1 patient, 1.0 ng/mg protein, was in the normal range, the levels in the
      type 3 samples ranged from 14 to 32 ng/mg protein, and in the type 2 samples from
      24 to 437 ng/mg protein, with the highest values detected in two fetuses with
      hydrops fetalis. The elevated levels found in brains from patients with
      neuronopathic Gaucher disease support the hypothesis that glucosylsphingosine may
      contribute to the nervous system involvement in these patients.

PMID- 12208132
TI  - Prosaposin: threshold rescue and analysis of the "neuritogenic" region in
      transgenic mice.
AB  - Prosaposin is the precursor of four glycoprotein activators (saposins) for
      lysosomal hydrolases. Intact prosaposin also has lipid transfer properties in
      vitro as well as neuritogenic effects ex vivo and in vivo. Such "neuritogenic"
      effects of saposin C were evaluated in vivo using transgenic mice with prosaposin
      cDNAs having normal (PS-N) or mutated neuritogenic region. The mutant prosaposin
      cDNA (PS-CBC) encoded a chimeric saposin C that contained the non-neuritogenic
      sequence of saposin B, but retained acid beta-glucosidase (GCase) activation
      effects. When driven by the PGK (3-phosphoglycerate kinase) promoter, transgene
      expression was highest in the cerebrum for any of the transgenes (range from 15%
      to 42% of wild-type). Low levels were in visceral tissues. Prosaposin knock-out
      (PS-/-) mice expressing N or CBC transgenes, even at low levels, had delayed
      onset of neurologic signs and neuropathology, and significant lengthening of life
      span (from 1.7- to 7-fold) with age dependent partial correction of GlcCer and
      LacCer accumulation in the brain. Neuropathologic progression and neuronal
      glycosphingolipid storage were related directly to the transgene expression
      levels in the brain. Purkinje cell loss was age dependent. Gross brain and
      neuronal organizations were indistinguishable in PS-/- mice with or without the
      various transgenes, albeit the phenotype appeared later in the mice with
      transgenes. These studies show the degree of neuropathologic manifestations in
      each transgenic line depended on expression level rather than on the nature of
      the transgene. These studies also show in vivo localization of the GCase
      activation region to the carboxy terminal half of saposin C and the lack of a
      significant gross trophic effect of saposin C on CNS organization in vivo.

PMID- 12208133
TI  - Characterization of a carbohydrate response element regulating the gene for human
      galactose-1-phosphate uridyltransferase.
AB  - Human galactose-1-phosphate uridyltransferase (hGALT) is a central enzyme in the
      conserved pathway by which galactose is converted to energy, UDP-galactose and
      UDP-glucose. A natural mutation that deleted -119 to -116 bp (delGTCA) of the
      promoter decreased hGALT mRNA and enzyme activity and prompted analysis of hGALT
      gene regulation. Regulatory domains were identified by inspection and confirmed
      in a reporter system. Previous studies by others were confirmed that HepG2 cells
      grown in D-glucose increased hGALT enzyme activity and mRNA by 30%. We extended
      these observations by sequencing the promoter region and identifying a potential
      carbohydrate response element (ChoRE). The response to glucose rose to 190% when
      a plasmid construct containing a luciferase reporter and only the -165 bp region
      as a promoter was transfected into HepG2 and NIH:OVCAR-3. By contrast,
      fibroblasts transfected with the identical construct failed to respond to
      glucose. Within the -165 bp region there were two enhancer (E-box) motifs that
      encompassed the delGTCA mutation. The deletion diminished the positive regulatory
      response, but an additional GTCA repeat unexpectedly increased the response.
      Using this postulated ChoRE as a probe in electrophoretic mobility shift assays,
      multiple nuclear proteins bound and one was identified as a member of the
      basic/helix-loop-helix/leucine zipper enhancer-binding (b/HLH/LZ) family.
      Increased binding of proteins correlated with increased hGALT expression when the
      spacing between E-box motifs was enlarged but the carbohydrate response was
      dampened. When the 3(')E-box was mutated, b/HLH/LZ binding and gene expression
      were abolished. We conclude that the hGALT promoter region contains a ChoRE in
      which the spacing between and the sequence of its E-box motifs are critical. One
      nuclear protein of the b/HLH/LZ family is necessary, but not sufficient for the
      carbohydrate response.

PMID- 12208134
TI  - The curly-tail (ct) mouse, an animal model of neural tube defects, displays
      altered homocysteine metabolism without folate responsiveness or a defect in
      Mthfr.
AB  - Maternal mild hyperhomocysteinemia is associated with increased risk for bearing
      children with neural tube defects (NTD). Folate intake corrects
      hyperhomocysteinemia and prevents up to 70% of NTD. The curly-tail (ct) mouse, an
      animal model for NTD, has been suggested to display features that closely
      resemble the human defect. We therefore investigated folate metabolism in ct
      mice. On control and folate-/choline-deficient diets, ct mice exhibited higher
      plasma homocysteine levels than control C57Bl/6 mice. This increase was
      associated with increased liver S-Adenosylhomocysteine and decreased S
      adenosylmethionine:S-adenosylhomocysteine (SAM/SAH) ratios. Since the ct locus
      maps in close proximity to the gene for methylenetetrahydrofolate reductase
      (Mthfr), a modifier of homocysteine levels in man, we also assayed Mthfr activity
      and sequenced the 5(') regulatory region; these experiments suggested that Mthfr
      is not defective in the ct strain. Finally, we examined the influence of dietary
      folate on NTD incidence in the ct strain, but did not identify significant
      differences among the four diets used in the study. Our work suggests that
      altered homocysteine metabolism may contribute to the pathogenetic mechanism of
      the ct defect, but, unlike human NTD, nutritional or genetic deficiencies in
      folate metabolism do not appear to play a significant direct role.

PMID- 12208135
TI  - The impact of phenylketonuria on folate metabolism.
AB  - Several reports indicate that biopterin and folate pathways may interact. We
      examined folate metabolism in PKU patients where hyperphenylalaninaemia leads to
      a likely excess of THB. We found an increase in total HPLC determined red cell
      folate in PKU (p=0.0422): specifically, there was an increase in total formyl
      H(4)folate (p=0.0002) and H(4)folate (p< or =0.0001), and decrease in total 5
      methyl-H(4)folate in PKU patients. At the level of individual oligo-gamma
      glutamyl coenzymes, we found that formyl-H(4)folate polyglutamates were virtually
      all increased in PKU (p=0.0223, 0.0004, 0.0004, 0.0012, and 0.0008 for di-, tri-,
      tetra-, penta-, and deca-gamma-glutamyl formyl-H(4)folate coenzymes,
      respectively). Hcy levels did not differ between clinical groups, indicating that
      folate dependent-Hcy remethylation is not compromised as a consequence of an
      altered PKU folate disposition. In nature, pentaglutamyl folates are considered
      the metabolically favoured coenzymes (optimum K(m) for dependent enzymes). The
      presented data support this-we found that red cell pentaglutamates gave the best
      measure of metabolism; pentaglutamyl formyl-H(4)folate increased in PKU
      (p=0.0012) and related methenyls behaved similarly, while, pentaglutamyl 5-methyl
      H(4)folate and pentaglutamyl H(4)folate decreased (p< or =0.0001 and 0.0265,
      respectively). Furthermore, pentaglutamates showed the best correlations between
      one-carbon oxidation states of folate, as well as with Hcy (p=0.0003 r=-0.54, 95%
      CI; -0.724 to -0.272). That PKU might influence folate metabolism in some way is
      unsurprising: patients with DHPR deficiency accumulate DHB and develop secondary
      folate deficiency-responsive only to reduced folates, while CSF levels of THB are
      significantly correlated to monoamines and red cell folate in depression. Further
      studies to confirm the present findings and to ascertain precisely what mechanism
      operates in PKU that impacts upon folate homeostasis so profoundly are required.

PMID- 12208136
TI  - Comparison of epidermal keratinocytes and dermal fibroblasts as potential target
      cells for somatic gene therapy of phenylketonuria.
AB  - Phenylketonuria (PKU) is caused by deficiency of phenylalanine hydroxylase (PAH)
      and increased levels of phenylalanine. PAH requires the cofactor BH(4) to
      function and the rate-limiting step in the synthesis of BH(4) is GTP
      cyclohydrolase I (GTP-CH). The skin is a potential target tissue for PKU gene
      therapy. We have previously shown that overexpression of PAH and GTP-CH in
      primary human keratinocytes leads to high levels of phenylalanine clearance
      without BH(4) supplementation [Gene Ther. 7 (2000) 1971]. Here, we investigate
      the capacity of fibroblasts, another cell type from the skin, to metabolize
      phenylalanine. After retroviral gene transfer of PAH and GTP-CH both normal and
      PKU patient fibroblasts were able to metabolize phenylalanine, however, in lower
      amounts compared to genetically modified keratinocytes. Further comparative
      analyses between keratinocytes and fibroblasts revealed a higher copy number of
      transgenes in keratinocytes and also a higher metabolic capacity.

PMID- 12208137
TI  - Impact of patient mutations on heterodimer formation and function in human
      galactose-1-P uridylyltransferase.
AB  - Impairment of the human enzyme galactose-1-P uridylyltransferase (hGALT) results
      in the potentially lethal disorder, galactosemia. One of the fundamental
      questions with regard to this dimeric enzyme involves the possible influence of
      patient mutations on heterodimer formation and activity. Indeed, considering that
      many if not most galactosemia patients are compound heterozygotes, this is an
      issue of clinical as well as basic science interest. We have utilized a yeast
      expression system for the human enzyme to test whether each of a small number of
      mutations in hGALT (S135L, F171S, F171W, Q188R, N314D, and R333W) impact either
      heterodimer formation or function. Our results clearly demonstrate that while a
      majority of the alleles tested show precisely random patterns of subunit
      assortment, two deviate slightly but significantly from this pattern. Similarly,
      while some heterodimers exhibit apparent independence of subunit activity, others
      do not. These data not only demonstrate that common patient mutations in hGALT
      can influence both heterodimer formation and function in heterozygotes, they
      further raise the question of whether such interactions may also occur between
      different mutant alleles in compound heterozygotes (i.e., patients). Indeed, such
      influences may underlie some of the biochemical and clinical heterogeneity
      observed in the galactosemia patient population.

PMID- 12208138
TI  - Quantitative fibroblast acylcarnitine profiles in mitochondrial fatty acid beta
      oxidation defects: phenotype/metabolite correlations.
AB  - Mitochondrial fatty acid beta-oxidation (FAO) disorders are clinically and
      biochemically heterogeneous diseases mainly associated with intolerance to
      catabolic stress. These disorders can now be detected pre-symptomatically by
      newborn screening, and thus the clinical phenotype in an individual patient may
      be unclear. Correlation of clinical severity with concentrations of acylcarnitine
      species was investigated in fibroblasts from FAO-deficient patients presenting
      with various phenotypes and asymptomatic neonates detected by newborn screening.
      Intact cells were incubated in medium containing deuterium-labelled hexadecanoic
      acid and L-carnitine for 72h, and the accumulated acylcarnitines in the culture
      medium analysed using electrospray tandem mass spectrometery. Fibroblasts from
      patients with long-chain FAO disorders presenting at an early age and with poor
      clinical outcomes accumulated higher concentrations of long-chain acylcarnitine
      species compared with those from patients with milder phenotypes. This suggests
      that the in vitro quantitative acylcarnitine profiling could perhaps predict the
      prognosis of some FAO defects. This would be particularly useful information for
      the asymptomatic/pre-symptomatic FAO-deficient infant detected by the expanded
      newborn screening program, in whom the risk of developing symptoms later in life
      is not known.

PMID- 12208139
TI  - The rat shorn mutation (shn) maps between D7Got143 and D7Rat94.
AB  - The recessive shorn (shn) mutation in the rat generates an almost complete
      absence of normal hair. Previous analysis of 85 backcross rats typed for shn
      generated hypotrichosis located this marker between the telomere and D7Mgh1 on
      distal rat Chromosome 7. Here, we present a microsatellite polymorphism analysis
      of a 184-member backcross panel-including 99 new rats-that places shn within a
      2.7cM interval between markers D7Got143 and D7Rat94. In addition, this analysis
      has allowed meiotic ordering of 18 microsatellite markers-including 10 D7Got
      markers previously positioned only by radiation reduced hybrid analysis-across
      the 16.8cM region between D7Mit16 (Cyp2d4) and D7Rat94. Our inability to
      meiotically separate shn from 8 microsatellite markers (mapped by others over
      some 2-4cM or more than 40cR of genetic distance) suggests that the shn mutation
      may result from a chromosomal rearrangement that suppresses recombination
      throughout this interval.

PMID- 12208140
TI  - The bicistronic MOCS1 gene has alternative start codons on two mutually exclusive
      exons.
AB  - The bicistronic MOCS1 gene encodes two enzymatic activities that are necessary
      for the biosynthesis of the molybdenum cofactor (MoCo). Mutations in either of
      the two consecutive open reading frames are responsible for the majority of MoCo
      deficiency cases and result in a complementation group A phenotype. Two cDNA
      sequences have been described, which differ in the 5' sequence and encode for two
      forms of the protein MOCS1A with variable N-terminal sequences. We have
      reinvestigated the corresponding region by means of cDNA analysis and databank
      searches. This revealed three different splice variants, including two mutually
      exclusive first exons and a facultative intron. All three forms can be found in
      eight different human tissues in a constant ratio, which excludes tissue
      specificity of the different isoforms.

PMID- 12208141
TI  - Pyruvate dehydrogenase deficiency as a result of splice-site mutations in the
      PDX1 gene.
AB  - Mutations in the E3-binding protein component of pyruvate dehydrogenase complex
      have been demonstrated in a few cases of Leigh syndrome. We report that two
      mutations previously detected in the E3-binding protein cDNA are the consequence
      of splice-site mutations. Both involved a single base substitution in the
      conserved dinucleotides of splice junctions, one leading to skipping of an exon
      and the other, to activation of a cryptic site. Our findings add to the
      understanding of molecular basis of E3-binding protein deficiency and indicate
      yet again the high frequency of splicing mutations in this gene.

PMID- 12208142
TI  - Structure of human succinic semialdehyde dehydrogenase gene: identification of
      promoter region and alternatively processed isoforms.
AB  - Mitochondrial NAD(+)-dependent succinic semialdehyde dehydrogenase (ALDH5A1,
      SSADH) represents the last enzyme in the GABA catabolism and irreversibly
      oxidizes SSA to succinate. In human, SSADH deficiency results in 4-hydroxybutyric
      aciduria, an autosomal recessive disorder due to an accumulation of GABA and 4
      hydroxybutyric acid in the CNS. We already identified SSADH gene on human
      chromosome 6p22 and characterized the coding region. Furthermore, we described
      the first two mutations causing the disease. We report here the complete cDNA and
      genomic structure of the gene. A single transcription start site was identified
      by RNase protection 122 bp upstream of the ATG. EST database search and reporter
      gene constructs of the 3(') genomic region showed that the two major SSADH mRNA
      isoforms are due to alternative polyadenylation sites. The two mRNAs of 1827 and
      5225 nt were analyzed for differential stability and translation efficiency. The
      analysis of mRNA turnover showed that both SSADH transcripts are equally stable.
      Similarly, a measurement of polysomal association capability of the two GFP-SSADH
      reporter mRNAs (containing the 3' UTR regions of the two SSADH mRNAs) did not
      reveal any difference. However, we cannot exclude the fact that differential
      properties could be restricted to particular physiological conditions and/or
      specific tissues. We have also identified an alternatively spliced small exon,
      which may lead to a novel isoform of the enzyme. Furthermore, we report here on
      naturally occurring missense variants, which may significantly contribute to
      inter-individual variation of SSADH activity, possibly influencing GABA and GHB
      endogenous levels.

PMID- 12208143
TI  - Fizzy-related RNA expression patterns in mammalian development and cell lines.

PMID- 12208144
TI  - In randomized controlled trials, should subjects in both placebo and drug groups
      be expected to guess that they are taking drug 50% of the time?
AB  - Part of the design of some randomized controlled trials has included asking
      patients to guess whether they are taking placebo or active drug. Some authors
      have stated that in randomized, double-blind placebo-controlled clinical trials
      patients in each group should guess that they are taking placebo half the time.
      However, this pattern should occur only under a limited set of circumstances.
      This paper explores the factors that affect the guess and the role of the guess
      in understanding both the establishment and the maintenance of the blind. It
      suggests that more than half of those in the treatment group should guess they
      are taking active drug if treatment or side-effects are powerful. Though the
      randomized controlled trial has become the paradigmatic tool to assess treatment
      efficacy, studies are still needed to validate key assumptions make by
      investigators and the effect of violation of these assumptions on study outcomes.

PMID- 12208145
TI  - Establishment, maintenance, and remodeling of curvature in biology.
AB  - A new hypothesis is presented, which explains how exponential tissue
      concentration gradients of biphasic morphogens that inhibit and stimulate basic
      growth rates of cells at high and low concentration respectively, determine
      curvatures of folds and invaginations, tubular, dome-shaped, lenticular, and
      spherical biological structures. For example, TGF-beta induces endothelial cells
      and smooth muscle cells to form tubular, vessel-like structures in vitro and
      blood vessels in vivo. The morphogen modulates cell growth rates via inhibitory
      and stimulatory receptor pathways respectively, forming a concave curvature as
      seen from the source concentration end of a radial, vessel-wall
      diffusion/perfusion driven exponential morphogen concentration gradient. From the
      source, inhibition declines along the radial gradient, switching to increasing
      stimulation beyond a neutral point, at which growth inhibition equals growth
      stimulation. The source concentration, shape of the gradient, and nature of the
      inhibitory and stimulatory pathways determine mural curvature, independent of
      mural-cell basic growth rate.

PMID- 12208147
TI  - Is diabetic hypercoagulability an acquired annexinopathy? Glycation of annexin II
      as a putative mechanism for impaired fibrinolysis in diabetic patients.
AB  - Diabetics die mainly from thrombotic complications and there is clear evidence
      that diabetes is a hypercoagulable state. Epidemiological and prospective
      intervention data link hyperglycemia to vascular complications and glycation of
      proteins is one favored molecular basis to explain this fact. Cell surface
      receptors may support fibrinolytic surveillance in both intravascular and
      extravascular locations by stimulating plasmin generation and by protecting
      plasmin from its inhibitors. The existing experimental evidence suggests that
      annexin II in its tetrameric form is the main physiological receptor for
      plasminogen on the extracellular surface of endothelial cells. We have recently
      shown that annexin II is an extremely vulnerable target for glycation, quickly
      responding to restoration of normoglycemia. We hypothesize that glycation of
      endothelial membrane annexin II impairs the appropriate formation of the
      plasminogen/tissue plasminogen activator/annexin II complex, disrupting a key
      regulatory mechanism in fibrinolytic vigilance. This would in turn produce
      decreased fibrinolytic activity and indirectly promote a thrombophilic state in
      diabetic patients. We base our hypothesis on our observation and on evidence for
      the mechanism of action of two major independent risk factors for CV events:
      lipoprotein (a) and hyperhomocysteinemia. Binding of plasminogen to annexin II is
      inhibited by Lp (a) and binding of tissue plasminogen activator to annexin II is
      blocked by homocysteine. If our hypothesis is correct, one of the components of
      the increased thrombogenicity seen in diabetic patients might then be an acquired
      annexinopathy.

PMID- 12208146
TI  - Is lead exposure the principal cause of essential hypertension?
AB  - Lead is a ubiquitous toxin, known to have adverse effects on the body even at low
      levels of exposure. In this review we explore whether low lead may be the
      principal or a major contributory cause of essential hypertension, and whether
      removal of lead from the environment may eventually reduce both the overall
      incidence of hypertension and the increased incidence with aging.

PMID- 12208148
TI  - The origin of humor.
AB  - Humor is spread throughout every culture on earth and occupies a large portion of
      our literature and social interaction. It is so deeply rooted in our culture that
      it may be a defining characteristic of our species. Yet there has been
      comparatively little effort to understand its origin. According to the Accepted
      Theory of Humor all jokes begin with a buildup of tension while an initial
      paradigm is formed. When the punch line occurs the subject must realign his
      thinking to accommodate the differences between the initial paradigm and the
      sudden burst of new information. The Mind Reading Hypothesis extends the accepted
      theory of humor to include a relationship between the observer and the subject of
      the humor. The actual source of amusement is the observation of the resolution in
      the mind of the subject of the collision between old perception and new reality.

PMID- 12208149
TI  - The possible role of the cerebellum in autism/PDD: disruption of a multisensory
      feedback loop.
AB  - Autism and pervasive developmental disorder (PDD) are characterized by
      impairments in socialization and communication, and by restricted and stereotypic
      patterns of behavior. Associated symptoms or features of autism/PDD include
      problems with attention and orientation, and an odd response to the environment
      and sensory stimuli. Persons with autism/PDD can over or under respond or react
      to sensation. Evidence suggests that there is aberrant brain structure in this
      disorder, particularly in the cerebellum. This paper will attempt to show a
      possible relationship between the pathology in the cerebellum and the
      symptomatology seen in autism/PDD with an emphasis on the sensory issues.

PMID- 12208150
TI  - Amplification of extracellular nucleotide-induced leukocyte(s) degranulation by
      contingent autocrine and paracrine mode of leukotriene-mediated chemokine
      receptor activation.
AB  - Extracellular nucleotide-induced stimulation and activation of peripheral blood
      leukocytes and subsequent degranulation play a critical role in immediate-type
      hypersensitivity reaction and other inflammatory diseases. The extracellular
      nucleotides stimulate a P2Y receptor(s) on human PMN with the pharmacological
      profile similar to that of the P2Y2 receptor. Upon activation of P2Y2,
      arachidonic acid, formed from the membrane bound lipids by phospholipase A2,
      which subsequently metabolized by 5-lipoxygenase to form the leukotrienes. Of the
      several leukotrienes generated, LTB(4) is a potent pro-inflammatory chemokine.
      Upon its release LTB(4) binds to the PMN in a paracrine manner and also other
      leukocytes such as monocytes at the site of vascular injury, leading to an
      accelerated rate of degranulation. It is known that LTA(4) formed in the 5
      lipoxygenase pathway in PMN could be released from PMN by receptor-mediated
      transport. Upon its release, the monocytes, erythrocytes, platelet, endothelial
      or smooth muscle cells can take up LTA(4). The endogenous LTA(4) hydrolase form
      the LTB(4) from LTA(4) in erythrocytes, platelet, endothelial or smooth muscle
      cells. As in PMN, LTB(4) is released from these cells via receptor-mediated
      transport to the extracellular milieu. Thus, released LTB(4) most likely acts as
      potentially accelerating factor in PMN and MN degranulation through its receptor
      specific binding. It is not known whether any LTB(4) receptor exists in cytoplasm
      in any given cell type and also, the existence of any other signaling cascade for
      the extracellular nucleotide-induced leukocyte degranulation. Thus, it is
      convincing that the extracellular nucleotides released from the activated
      platelets and other damaged cell types exacerbate the inflammatory response by
      leukotriene generation. In turn the leukotriene will act in both autocrine and
      paracrine manner to amplify the degranulation processes in leukocytes invoked by
      extracellular nucleotides.

PMID- 12208151
TI  - Role of protease-activated receptors in neutrophil degranulation.
AB  - Inflammation is a process culminated by cellular components and soluble mediators
      act in concert to evolve a sustainable process to impart distress in vascularized
      tissue. The role of thrombin receptors in neutrophil degranulation is not fully
      understood. Thrombin-mediated signaling has been shown to occur at least in part
      by a family of G protein-coupled protease-activated receptors (PARs). Protease
      activated receptors-1 (PAR1) is the prototype for understanding on the
      fundamental signaling mechanism and related characterization. The inference of
      thrombin receptors and various synthetic ligand formulations on neutrophil
      degranulation ascertained an enormous disparity in the response by human donors.
      Based on the previous reports and supposition in perpetuity, it is hypothesized
      that thrombin through its receptor, and its subtypes, may very improbably have
      any functional role in PMN degranulation.

PMID- 12208152
TI  - Policosanol safely down-regulates HMG-CoA reductase - potential as a component of
      the Esselstyn regimen.
AB  - Many of the wide-ranging health benefits conferred by statin therapy are
      mediated, not by reductions in LDL cholesterol, but rather by inhibition of
      isoprenylation reactions essential to the activation of Rho family GTPases; this
      may be the mechanism primarily responsible for the favorable impact of statins on
      risk for ischemic stroke, senile dementia, and fractures, as well as the anti
      hypertensive and platelet-stabilizing actions of these drugs. Indeed, the extent
      of these benefits is such as to suggest that most adults would be wise to take
      statins; however, owing to the significant expense of statin therapy, as well as
      to the potential for dangerous side effects that mandates regular physician
      follow-up, this strategy appears impractical. However, policosanol, a mixture of
      long-chain aliphatic alcohols extractable from sugar cane wax, has shown
      cholesterol-lowering potency comparable to that of statins, and yet appears to be
      devoid of toxic risk. Recent evidence indicates that policosanol down-regulates
      cellular expression of HMG-CoA reductase, and thus has the potential to suppress
      isoprenylation reactions much like statins do. Consistent with this possibility,
      the results of certain clinical and animal studies demonstrate that policosanol
      has many effects analogous to those of statins that are not likely explained by
      reductions of LDL cholesterol. However, unlike statins, policosanol does not
      directly inhibit HMG-CoA reductase, and even in high concentrations it fails to
      down-regulate this enzyme by more than 50% - thus likely accounting for the
      safety of this nutraceutical. In light of the fact that policosanol is quite
      inexpensive and is becoming available as a non-prescription dietary supplement,
      it may represent a practical resource that could enable the general public to
      enjoy health benefits comparable to those conferred by statins. In a long-term
      clinical study enrolling patients with significant symptomatic coronary disease,
      Esselstyn has demonstrated that a low-fat, whole-food vegan diet, coupled with
      sufficient statin therapy to maintain serum cholesterol below 150 mg/dL, can stop
      the progression of coronary disease and virtually eliminate further risk for
      heart attack. A comparable regimen, in which policosanol is used in place of
      statins, may represent a practical strategy whereby nearly everyone willing to
      commit to health-protective eating can either prevent coronary disease, or
      prevent pre-existing coronary disease from progressing to a life-threatening
      event.

PMID- 12208154
TI  - Live virus vaccination near a pregnancy: flawed policies, tragic results.
AB  - Vaccination of women with live virus vaccines around conception has always been
      contraindicated by the Center for Disease Control and Prevention (CDC) and the
      vaccine manufacturer because of potential risks to the fetus. Nevertheless this
      dangerous practice occurs and is associated with maternal health problems and a
      very high incidence of early-onset autism in the children. Postpartum vaccination
      with live virus vaccines has been recommended by the CDC, and described as
      'convenient' by the vaccine manufacturer. This 'routine practice' may lead to
      health and is also associated with many health and obstetrical problems in the
      recipient, and is frequently associated with autism in both current and future
      children. Re-vaccination often fails to produce immunity, the very reason for
      which it was recommended.

PMID- 12208153
TI  - Postpartum live virus vaccination: lessons from veterinary medicine.
AB  - Pregnant rubella-susceptible women are often revaccinated during the postpartum
      period with the Measles, Mumps, and Rubella vaccine (MMR). It is known that the
      rubella virus from vaccine is secreted in breast milk and persists in the nose
      and throat for up to 28 days but it is not known whether the measles and mumps
      viruses are similarly secreted. It is probable the measles virus from vaccine is.

PMID- 12208155
TI  - Adaptive activity of neural structures -- a thermodynamic approach.
AB  - The underlying mechanisms of behavioral functions at different levels of
      organization of the nervous system are not yet fully understood. No satisfactory
      answers have been supplied to the question of how do brain subsystems operate to
      ensure the adaptive behavior of the organism. In our view the answer to these
      complex questions lies in the physical chemistry of colloidal systems and moving
      boundaries. The latter coordinate metabolic, transport, and signal functions,
      while glial cells are active modulatory elements in signal transmission. This
      paper shows both theoretically and experimentally that optimal functioning of the
      brain at all its levels is determined by and based on the laws of thermodynamics
      of colloidal-electrolyte systems.

PMID- 12208156
TI  - Potential role of advanced glycosylation end products in promoting restenosis in
      diabetes and renal failure.
AB  - Diabetes and renal failure have been associated with extremely high restenosis
      rates following successful angioplasty, resulting in increased morbidity and
      mortality. Advanced glycosylation end products (AGEs) accumulate in vascular
      tissues with aging and at an accelerated rate in diabetes and renal failure. AGEs
      are particularly abundant at sites of atherosclerotic lesions. AGEs interact with
      specific receptors (RAGE) present on all cells relevant to the restenosis process
      including inflammatory cells and smooth muscle cells. AGEs-RAGE interaction in
      vessel wall may lead to inflammation, smooth muscle cell proliferation, and
      extracellular matrix production, culminating in exaggerated intimal hyperplasia
      and restenosis. Following arterial injury, the interaction of AGEs with monocytes
      expressing RAGE can promote migration of inflammatory cells into the lesion and
      subsequent release of growth factors and cytokines. Binding of AGEs-RAGE on
      smooth muscle cells increases chemotactic migration and cellular proliferation.
      AGEs trigger the generation of reactive oxygen species, and upregulate the
      multifunctional transcription factor NF-kappa B. Finally, AGEs can augment
      extracellular matrix production by upregulating transforming growth factor-beta.
      Thus, accumulation of AGEs in vessel wall provides a common mechanism for the
      high restenosis rates of patients with diabetes and renal failure.

PMID- 12208157
TI  - Does the pineal gland have a role in the psychological mechanisms involved in the
      progression of cancer?
AB  - Psychological factors, e.g., depression and psychological stress have been
      implicated in the progress of cancer. Similarly, the pineal gland and its
      principal secretion, melatonin, are known to influence the initiation and
      progress of cancer. Furthermore, changes in melatonin secretion have been linked
      with psychological stress and depression, and both the pineal gland and the
      cerebral cortex act via the limbic system in producing their effects. Both
      psychological stress and melatonin affect the immune system, as does the
      hypothalamus and the autonomic nervous system. The pineal gland has both a direct
      effect on cancer, and via the immune system. Psychological treatment and
      melatonin treatment have both been found to alleviate the course of cancer
      clinically. It is thus hypothesized that the pineal gland, and melatonin, are
      involved in the mechanism of psychological effects in the promotion of the
      progress of cancer.

PMID- 12208158
TI  - 'Twist theory' for the roles of estrogen and testosterone in the process of
      spermatogenesis.
AB  - Estrogen and testosterone have different effects on different steps of
      spermatogenesis and for each step optimal levels of estrogen and testosterone are
      different. The effects of these hormones behave as if 'twisted' from one end to
      the other end of the spectrum of steps of spermatogenesis. A graphic model is
      presented to explain this 'Twist Theory'.

PMID- 12208159
TI  - Matrix metalloproteinase inhibitor therapy to prevent complications as well as
      therapy for Ehler-Danlos syndrome.
AB  - Matrixmetalloproteinase inhibitors have been developed as anti-cancer agents.
      Their usage in pancreatic cancer and other such malignancies is under trial at
      present. An interesting undesired-effect of one of these agents is contracture of
      the hand. Ehler-Danlos syndrome is an inherited group of diseases with varying
      types. At present there is no known treatment or prevention for the complications
      associated with this inherited condition. Sometimes it is the adverse events of a
      drug, which provides an insight into its efficacy for another indication. It is
      hereby being hypothesized that the matrixmetalloproteinase inhibitors especially
      marimastat may be an effective drug for treatment of Ehler-Danlos syndrome and/or
      prevention of its major complications.

PMID- 12208160
TI  - What is the genetic factor in migraine?
AB  - Migraine is frequently assumed to have an hereditary origin, but what this
      hereditary factor is, no one really knows. Researchers are currently trying to
      find defects in genes which could either cause, or tend towards, the development
      of migraine. This approach is deemed mistaken for two reasons: firstly, pain,
      being only a signal of an essential monitoring system, cannot be an inheritable
      factor on its own without the accompanying physiological or pathological
      processes which give rise to it; and secondly, physicians, almost universally,
      fail to examine a large part of the head, viz., the mandible and maxillae and
      their appendages, before making their diagnoses or providing treatment, thereby
      contravening the fundamental principle of properly examining patients. It is
      hereby suggested, and evidence is offered showing that impacted teeth could be
      the long sought-after 'hereditary' factor causing migraine.

PMID- 12208161
TI  - Potential involvement of copper and thiol-disulphide interchange in prion
      proteins' conformational conversion.
AB  - The prion protein PrP(C) in transmissible spongiform encephalopathy converts to
      the pathogenic isoform PrP(Sc) containing less alpha-helical structure and a
      greater beta-pleated sheet content. The stability of PrP(C) protein is partly
      dependent on the disulphide bond between two alpha-helices designated B and C.
      Further stability could arise from ligand complexes of Cu(II) ions formed with
      carboxylic acid side chains in PrP(C). Electron spin resonance (E.S.R.) spectra
      and atomic absorption measurements have shown for alpha-keratin that the
      formation of ligands by Cu(II) is 10(2) more rapid than interaction of Cu(II)
      with ionised thiols X-S(-) which form X-S-Cu(+). X-S(-) destabilises disulphide
      bonds by thiol-disulphide interchange. When insufficient Cu(II) is present to
      form ligands with all available sites in PrP(C) then unblocked X-S(-) groups
      could potentially destabilise the disulphide bonds by thiol-disulphide
      interchange followed by reformation of the disulphide bond in the beta form of
      PrP(Sc) and the release of X-S(-) to interact with other PrP(C).

PMID- 12208162
TI  - Epidemic pathogenic selection: an explanation for hereditary hemochromatosis?
AB  - Hereditary hemochromatosis (HH) is a disorder associated with progressive iron
      overload and deposition in multiple organs. It is the most common inherited
      single gene disorder in people of Northern and Western European descent. About
      80% of individuals of European descent with HH are homozygous for a cysteine-to
      tyrosine substitution (C282Y) in the gene now called HFE. The function of HFE
      protein, a major histocompatibility class I-like transmembrane protein, has not
      been fully elucidated. Three consequences of the C282Y mutation are lack of
      expression of HFE on the cellular surface, a lowered iron level in macrophages,
      and an increased rate of clearance of iron from the intestinal lumen. These
      changes could confer protection against certain pathogens early in life before
      iron overload occurs. Furthermore, the C282Y mutation might have been selected
      for during the European plagues caused by Yersinia spp. and other pathogens
      because of the conferred resistance to infection, i.e., by epidemic pathogenic
      selection.

PMID- 12208163
TI  - Role of selenium depletion in the etiopathogenesis of depression in patients with
      alcoholism [corrected].
AB  - Chronic heavy alcohol consumption adversely affects both macronutrients and
      micronutrients. Alcohol use affects selenium status. Considerable evidence
      suggests that selenium status may modify mental function. The author suggests
      that the effects of alcohol intake on mood, behavior, and cognition may be partly
      mediated by biological changes related to selenium deficiency. It has been
      observed that there is a trend towards the normalization of selenium levels in
      patients with alcoholism after a relatively short period of abstinence from
      alcohol. It has also been observed that when depression develops in persons with
      alcoholism, they are likely to improve fairly rapidly after a relatively short
      period of abstinence from alcohol without therapy aimed at the depressive
      symptoms. The author suggests that improvement in depressed patients after a
      period of abstinence from alcohol might be in part related to the normalization
      of selenium status. Treatment and prevention of comorbid alcoholism and mood
      disorders require more attention by research workers, practicing physicians, and
      the general public. Future studies of the etiology and pathogenesis of mood
      disorders in patients with alcoholism are merited.

PMID- 12208164
TI  - The ratio of 2nd to 4th digit length: a proxy for transactivation activity of the
      androgen receptor gene?
AB  - The androgen receptor gene (AR) contains a domain which includes a variable
      number of CAG sequences and alleles with low numbers of CAG repeats show high
      transactivation activity when complexed with testosterone. The ratio of 2nd and
      4th digit length (2D:4D) is negatively correlated with phenotypic effects of
      testosterone. Low numbers of CAG repeats and low 2D:4D are both associated with
      high sperm numbers and protection against breast cancer. This suggests that CAG
      number and 2D:4D are correlated i.e. low CAG number and low 2D:4D indicate high
      activation of androgen-responsive genes. Findings from AR studies predict that
      low 2D:4D will be associated with prostate and hepatocellular cancer,
      urolithiasis, ADHD, ankylosing spondylitis, spontaneous abortion, and polycystic
      ovaries, while high 2D:4D will be associated with motor neuron diseases and
      endometrial cancer. Findings from 2D:4D studies predict that short CAG length
      will be common in autism and Asperger's syndrome, while high numbers of CAG
      repeats will be found in men who are prone to early myocardial infarction.

PMID- 12208165
TI  - Antidiuretic hormone replacement therapy to prevent or ameliorate vasodilatory
      shock.
AB  - Vasodilatory shock is a syndrome with high mortality. It is becoming evident that
      depletion of antidiuretic hormone (ADH) after cardiac surgery or during sepsis
      plays an important role in the pathogenesis of this condition. Established
      vasodilatory shock responds well to exogenous ADH infusion. It is possible that
      preventing ADH depletion at an earlier stage may abrogate the onset of
      vasodilatory shock, or at least reduce its severity. This paper examines the
      evidence supporting this concept, and the potential areas of concern in
      considering this particular type of hormone replacement therapy.

PMID- 12208166
TI  - The leukocyte adhesiveness/aggregation test (LAAT) conveys information of
      biological relevance and is not a result of chance collision. Something more than
      another hypothesis.
AB  - The leukocyte adhesiveness/aggregation test is a sensitive marker for the
      detection of inflammation and for the assessment of its intensity. This has been
      convincingly shown by several independent groups as well as in various models of
      infection/inflammation. However, it has not been settled whether the concomitant
      appearance of leukocytosis and aggregation is a result of chance collision or
      not. We recently examined a group of individuals with proven acute
      infection/inflammation who had absolutely the same number of white blood cells in
      the peripheral blood and found significantly enhanced leukocyte
      adhesiveness/aggregation in patients as opposed to control. These findings
      clearly demonstrate that the phenomenon of leukocyte adhesiveness/aggregation
      does not result from a simple chance collision. It probably conveys a message of
      biological relevance reflecting both the appearance of cell adhesive molecules
      during activation as well as the contribution of plasmatic sticky proteins.

PMID- 12208167
TI  - Old antihypertensives as novel antineoplastics: angiotensin-I-converting enzyme
      inhibitors and angiotensin II type 1 receptor antagonists.
AB  - Angiogenesis, cellular growth and invasion of a cancer cell are attractive
      targets for new treatment strategies of malignancies in recent years. The
      evidences are accumulating that ACE inhibitors and angiotensin II type 1
      antagonists could be novel anti-angiogenic, anti-invasive, and even anti-growth
      agents against neoplastic tissues: The renin-angiotensin system promotes
      angiogenesis directly or indirectly and growth of neoplastic cell. Some tumors
      carry angiotensin II type 1 receptors. Angiotensin II antagonists and angiotensin
      I-converting enzyme inhibitors have shown some anti-neoplastic actions.
      Angiotensin II receptor blocker losartan antagonises platelets, which are thought
      to modulate via vascular endothelial growth factor. They may even protect the
      patient from the major toxicity of chemotherapy and/or radiotherapy,
      myelotoxicity, enabling us to give higher doses and end up with higher success
      rate. We believe that these agents can be useful on clinical grounds and suggest
      their incorporation into clinical studies.

PMID- 12208168
TI  - Anatomical basis of chronic pelvic pain syndrome: the ischial spine and pudendal
      nerve entrapment.
AB  - Chronic pelvic pain syndrome is a conundrum that may be explained partly by
      pudendal nerve entrapment (PNE), which causes neuropathic pain. In men with PNE,
      aberrant development and subsequent malpositioning of the ischial spine appear to
      be associated with athletic activities during their youth. The changes occur
      during the period of development and ossification of the spinous process of the
      ischium.

PMID- 12208169
TI  - Consumer-producer relationship and homeostasis.
AB  - Notion of consumers-producers co-operation allows better understanding of the
      basic mechanisms of homeostasis. This concept refers to the biological variables
      (BV) that are produced by tissues and organs (producers) and used for provision
      of functional activity of other organs and tissues (consumers). The rate of BV
      consumption is a major BV down-regulation factor, which participates in two kinds
      of imbalance: feedback and feedforward. When consumers are activates prior to
      producers, BV decrease and up-regulation forces are activated to counteract the
      decrease (feedback imbalance). Feedforward imbalance appears when producers are
      activated and BV consumption is postponed or suppressed. Prolonged feedforward
      imbalance is supposed to lead to chronic metabolic disturbances and diseases
      (obesitas, atherosclerosis, hypertension, NIDDM, Syndrome X, etc.).

PMID- 12208170
TI  - Do metastatic tumours from an unknown primary reflect angiogenic incompetence of
      the tumour at the primary site?--a hypothesis.
AB  - Metastases from unknown primary tumours (MUP) are not an uncommon clinical
      problem. A hypothesis that discusses the plausible role of neoangiogenesis, as a
      central theme in the development of MUPs, is presented. Invasive cancers, which
      cannot or do not switch to the angiogenic phenotype, remain subclinical. In
      situations where a non-angiogenic tumour attempts to grow beyond the volume that
      can be supported by the vasculature, marked apoptosis and cell turnover result.
      Tumours with a high cell turnover are biologically advanced. Thus, such
      subclinical tumours acquire a metastatic phenotype. In the viscera, metastases
      may remain dormant for varying periods until subclones with an angiogenic
      phenotype arise due to tumour evolution or they burn out. Visceral MUPs, due to
      their longer evolution, are biologically advanced and have dismal prognosis.
      Contrary to this, tumour cells reaching lymph nodes (LN) grow without acquiring
      any phenotypic or genotypic change, as angiogenesis is redundant for growth
      within the metastatic LNs.

PMID- 12208171
TI  - Minor thalassemia as a protective factor against cerebrovascular accidents.
AB  - Hypertension, hypercholesterolemia, and coronary artery disease are among the
      risk factors of cerebrovascular accidents. After age, hypertension is the most
      powerful stroke risk factor. Abnormalities of serum lipids are regarded as risk
      factors for cerebrovascular accidents. A significant reduction in stroke risk
      among persons treated with cholesterol-reducing medicines known as statins are
      reported. Stroke risk nearly doubles in those with antecedent coronary artery
      disease. Moreover, polycythemia and high hematocrit levels are considered to be
      potential stroke risk factors. Minor thalassemia is associated with decreased
      prevalence of arterial hypertension and myocardial infarction (the second effect
      observed only in males.) Total cholesterol and LDL levels are lower in minor
      thalassemics, as is the blood viscosity. Therefore, it could be hypothesized that
      minor thalassemia could afford some protection against cerebrovascular accidents.

PMID- 12208172
TI  - Malarial anaemia: a crossroad?
AB  - Despite the apparent frailty of a complex cycle, Plasmodium falciparum seems
      remarkably fit in its ability to escape human interventions. The red blood cell
      is central in a number of aspects of the cycle. Hence, hematocrit reduction is of
      paramount importance in vector survival and reproduction, gametocyte induction
      and infectiousness, and host pathology. Here, in the light of recent
      observations, the importance of anemia for P. falciparum is emphasized,
      suggesting that among populations at risk for malaria, the subgroup of anemic
      patients may be preferential amplifiers of the plasmodial cycle.

PMID- 12208173
TI  - Cell brain crystallization for cancer therapy.
AB  - Cancer remains one of the leading causes of death throughout the world. One of
      the important reasons why conventional treatments fail is the development of
      resistance to therapeutics. The dual effect concept and self-defense mechanism
      plus the threshold theory might in part explain the development of resistance,
      however, the primary cause is unclear. A novel theory, 'cell brain', where,
      selective crystallization of the 'brain' of a cell (comprising centrosome,
      centrioles and the connecting filaments) occurs, may be a potential alternate
      approach to cancer therapy.

PMID- 12208174
TI  - Parkinson's: another look.
AB  - Recent studies in the Parkinson's literature have cited a tuberculosis-like germ
      called Nocardia as being responsible for Parkinson's disease. Kohbata seemingly
      cemented a relationship between Nocardia and Parkinson's by finding serologic
      evidence in 20 of 20 Parkinson's patients, acknowledging that blood tests for
      Nocardia and the mycobacteria such as tuberculosis often cross-react, as they
      belong to the same order of bacteria, the Actinomycetales. Besides this
      difficulty in differentiation, a well-used medical school textbook of
      microbiology, Atlas, points out that even among experts, different observers may
      classify the same strain of bacteria as Nocardia or Mycobacterium tuberculosis.
      Parkinson's: another look is a theoretical article which presents compelling,
      well-documented evidence for an infectious cause for Parkinson's disease on
      historical, epidemiological, pharmacologic, microbiological, and biochemical
      levels.

PMID- 12208175
TI  - The possible role of prolactin in preeclampsia: 2001, a hypothesis revisited a
      quarter of century later.
AB  - A genetic predisposition (theory 1) to preeclampsia in a woman with or without
      risk factors, may lead to an immune maladaptation to pregnancy (theory 2) (Th1
      type of immune response predominance over Th2). In turn, they may contribute to
      an early defective 'switch' (quantitatively or out of timing) with a predominant
      decidual production of 16-kDa PRL over that of a 23-kDa PRL (our hypothesis),
      which induces an antiangiogenic process with a shallow invasion of the spiral
      arteries by the endovascular cytotrophoblast. Afterwards, a high-resistance
      arteriolar system and placental ischemia or hypoxia ensue, leading to endothelial
      cell dysfunction (theory 3) and an increased oxidative stress (theory 4). We are
      not proposing any strict chronological sequence of events, but the early
      occurrence (first 10 weeks) during pregnancy of the predominant decidual
      secretion of a 16-kDa PRL over that of 23-kDa PRL inducing a defective angiogenic
      process. No other specific mechanism(s) to explain the 'shallow' invasion of the
      spiral arteries has been previously proposed. Furthermore, it seems to happen
      early enough in pregnancy, as a 'very early change which may give a clue to the
      etiology,' as first suggested 25 years ago by Horrobin.

PMID- 12208176
TI  - Evidence that failure to conceive despite apparent correction of ovulatory
      defects by follicle-maturing drugs may be related to premature trophoblast
      invasion.
AB  - There is evidence that follicle-maturing drugs, especially when used for
      controlled ovarian hyperstimulation for in vitro fertilization-embryo transfer
      (IVF-ET) purposes, may be associated with lower pregnancy rates following ET
      related to a hostile uterine environment. It was assumed that this was related to
      implantation failure of the embryos. However, there is a possibility that the
      embryo may implant too soon into a uterine environment not ready for the invading
      trophoblast. To test this hypothesis a 34kDa protein known as the progesterone
      induced blocking factor (PIBF), which only rises after trophoblast invasion, was
      measured at the peri-implantation time 3 days after ET. The results showed a
      marked reduction in pregnancy rates per transfer in those positive for PIBF at
      this time especially in those receiving controlled ovarian hyperstimulation.
      Thus, these data suggested that premature trophoblast invasion rather than
      failure for embryos to implant may be the etiologic factor responsible for the
      adverse effect of controlled ovarian stimulation in the uterine environment.

PMID- 12208177
TI  - Osteoarthritis as an inevitable consequence of the structure of articular
      cartilage.
AB  - The hypothesis that osteoarthritis is an inevitable consequence of the structure
      of articular cartilage is proposed. Cartilage structure is viewed as an
      evolutionary solution to the optimization of articular cartilage function. A
      simplified model of the structural elements and constraints will be used to
      illustrate how the hypothesis leads to a mathematical solution and then a more
      realistic situation will be described, but not optimized rigorously. The goal for
      finding a solution will be to optimize the function of articular cartilage
      subject to the constraints of a biological tissue. In comparison, the structure
      of genuine articular cartilage will be discussed in the context of an optimal
      solution to the functional problem and, particularly, in relation to the disease
      of osteoarthritis.

PMID- 12208178
TI  - Three hypotheses linking bile to carcinogenesis in the gastrointestinal tract:
      certain bile salts have properties that may be used to complement chemotherapy.
AB  - The literature for the proliferative effect of bile acids on the GI tract has
      been reviewed and three hypotheses developed regarding their carcinogenicity.
      Considered as a unit, the GI tract is protected from this carcinogenicity in
      different ways in the esophagus, stomach, small bowel and colon. Uncharged BAs
      can enter the esophageal epithelial cells by reflux of gastroduodenal juices in
      humans, and in animals by surgical alteration of the GI tract or by adding bile
      concentrate to the diets, and this can initiate GERD and eventually cancer. Acid
      suppressant therapy used to treat GERD patients, converts stomach pH to >4. This
      will remove the charges on conjugated bile acids allowing them entry into the
      epithelium thus casting doubt on the efficacy of acid suppression. From these
      observations, we postulate that (a) uncharged BA in daily contact with the
      esophagus can cause GERD and eventually cancer. This might explain the cancers
      obtained by Fein et al. (b) Clinical trials designed to test the effectiveness of
      acid suppressants will be meaningless since up to approximately 87% of these
      patients (in one study) have bile in their refluxate, and this, combined with
      acid suppressants, will initiate carcinogenesis. (c) Bile reaching a colon made
      sterile by antibiotics or other means, will not be deconjugated and so, with
      pKa's of 2 and 4, will be uncharged and therefore can easily enter the colonic
      cells where the pH is >6. This should be of some concern, especially on a high
      fat diet when more bile enters the colon. A group of physicians noted that
      approximately 47% of patients with esophageal cancers also had some form of colon
      cancer and postulated that an etiological factor in the environment was
      responsible. Could this factor be bile? Reactions of certain bile salts with
      epithelial cells suggest a useful role for them in chemotherapy. Experiments to
      test hypotheses a, b and c are presented in the addendum.

PMID- 12208179
TI  - Cessation of reproduction: an analytic view of menopause.
AB  - While there is evidence for genetic control of ovarian and follicular
      development, only recently have reports appeared on genetic components involved
      in ovarian failure. Unlike predictions of a stable population, age at menarche is
      decreasing, while female life span is increasing. This leads to examination of
      genotype-environment interactions. Evolution of the large human brain size has
      been accompanied by a reduction in size of the gastrointestinal tract.
      Consequences, in terms of altered diet and effects on
      menarche/menstruation/menopause were discussed. In the earliest days of human
      evolution, genotoxic agents and marginal diets could have produced heritable
      changes in cessation of menstruation. Toxic alterations may still be apparent,
      such as epidemiological studies on the effects of smoking on age at menopause.
      Attempts to reconstruct some of the recent past history, from coprolites to
      findings in frozen human specimens, have to be extended still further into the
      past.

PMID- 12208180
TI  - Rheumatoid arthritis is auto-immunoreaction to collagen II in cartilage happened
      in synovial tissue.
AB  - Rheumatoid arthritis is complex and not clear on the mechanism of pathogenesis.
      On the basis of analysis of the symptom and pathology of rheumatoid arthritis
      patients, we raised a new hypothesis. The content of the hypothesis is as
      follows: (A) Collagen II or collagen II-Iike substance in human cartilage is the
      cross-autoantigen of some infecting virus or bacteria because of the structure's
      similarity. (B) The inflammation in synovial tissue is auto-immunoreaction to
      collagen II in cartilage. (C) The proliferation and attachment of synovial tissue
      to the surface of cartilage is due to the chemotaxis of collagen II in cartilage
      for the immunocytes in synovial tissue. (D) The collagenase secreted from
      synovial cells and immunocytes are the direct elements in the destruction of
      cartilage. The fallen collagen II from cartilage is one of the most important
      inducer on the synovial cells and immunocytes for the production of collagenase.

PMID- 12208181
TI  - Did schizophrenia change the course of English history? The mental illness of
      Henry VI.
AB  - Henry VI, King of England, at age 19 founded Eton College and King's College,
      Cambridge. At 31 he had a sudden, dramatic mental illness in which he was mute
      and unresponsive. Before, he had been paranoid, grandiose, and indecisive. After,
      he was apathetic with deterioration of ability, drive, interest and self-care,
      and hallucinations and religious delusions. This illness, which is consistent
      with a diagnosis of schizophrenia, robbed Henry of his personality, his crown,
      his wife, his only son, and his life. It led to three decades of brutal fighting
      for the crown (the 'Wars of the Roses') that resulted in a new dynasty with a
      dramatic impact on the country: the Tudors, Henry VIII, and Elizabeth I and their
      descendants. Henry's story illustrates how schizophrenia can devastate
      individuals and families and change the course of history and yet it raises
      questions about how achievement and illness are related.

PMID- 12208182
TI  - The use of in situ bone marrow stem cells for the treatment of various
      degenerative diseases.
AB  - The potential for tissue repair and regeneration is encouraging in the light of
      novel research on the plasticity of adult stem cells. Intense research efforts
      over the last 3 years have provided solid evidence for the continuous generation
      of many types of tissue cells from adult stem cells as a normal part of our
      physiology throughout development and adult life in mammals, including humans.
      This opens new therapeutic avenues for many clinical problems and provides
      alternative opportunities at a time when much attention has been brought to the
      issue of using embryonic stem cells for research purposes and for the development
      of treatments for various diseases. Embryonic stem cells are pluripotent cells
      characterized by nearly unlimited self-renewal and differentiation capacity.
      However, evidence has accumulated over the past few years, indicating that adult
      bone marrow stem cells might have pluripotent properties similar to those of
      embryonic stem cells. Based on a review of the literature we propose the
      hypothesis that in situ mobilization of stem cells from the bone marrow and their
      migration to various tissues is a normal physiological process of regeneration
      and repair and that therapeutic benefits can be generated with less invasive
      regimens than the removal and re-injection of stem cells, through the stimulation
      of normal stem cell migration. We further propose that effort should be made to
      identify natural compounds characterized by their ability to augment this normal
      process of mobilization and re-colonization of bone marrow stem cells for the
      potential treatment of various degenerative diseases.

PMID- 12208183
TI  - Lithium and antidepressants: inhibiting eicosanoids, stimulating immunity, and
      defeating microorganisms.
AB  - Infection-emerging, reemerging, antibiotic-resistant, and bioengineered
      increasingly threatens mankind. It is widely assumed that immunostimulating
      agents, were they to exist, would be ideal in battling microorganisms. Various
      investigators have established lithium and antidepressants as immunostimulants
      and antimicrobials and they have identified the mechanisms involved. Eicosanoids
      both depress immunity and activate microorganisms and lithium and antidepressants
      oppose eicosanoids. Such philosophers of science as Paul Feyerabend have argued
      that special interests invariably oppose revolutionary paradigms.

PMID- 12208184
TI  - The role of sperm-mediated gene transfer in genome mutation and evolution.
AB  - Contradictory evidence surrounds the claim that sperm cells are able to introduce
      exogenous DNA into the oocyte at the time of fertilisation. Although strong
      natural barriers exist against sperm-mediated gene transfer, such barriers are
      unlikely to be absolutely inviolable. If sperm cells can act as vectors for
      exogenous DNA, it follows that the genome of sexually reproducing animals may be
      subject to alteration by exogenous DNA sequences carried by sperm cells. At
      present there are insufficient data to permit quantification of the rate of sperm
      mediated gene transfer. The implications of sperm-mediated gene transfer are
      significant and include evolutionary effects on the mammalian genome and
      pathologies in humans from de novo mutations. Despite the absence of firm data,
      geneticists would be wise to be vigilant to the potential consequences of sperm
      mediated gene transfer.

PMID- 12208185
TI  - Mind from genes and neurons: a neurobiological model of Freudian psychology.
AB  - A hypothetical neurobiological model of Freud's architecture of the mind is
      presented in an attempt to unify concepts and data derived from molecular biology
      (e.g., genomic imprinting), systems neuroscience (e.g., neuroanatomochemical
      circuitries), evolutionary psychology (e.g., human mating strategies), and
      Freudian psychology. The model posits that events related to genomic imprinting
      can be regulated in a tissue-specific manner over the course of neural
      development such that imprinting along the matriline would favor the development
      of corticostriatal structures whereas imprinting along the patriline would favor
      the development of limbic-subcortical structures. A neuropsychological analysis
      of the brain requirements for successful mating presumably would put an
      evolutionary premium on the corticostriatal system (matrilineal) in men and
      limbic-subcortical systems (patrilineal) in women. Additionally, the model
      emphasizes that the ego and the super-ego of Freudian psychology are dependent on
      corticostriatal mechanisms (matriline-related), while the id is dependent on
      brainstem processes (patriline-related). It is hoped that the model herein
      presented has heuristic value for a rapprochement of psychoanalysis and
      neurobiology.

PMID- 12208186
TI  - Novel mechanism of action hypothesized for stellate ganglion block related to
      melatonin.
AB  - The mechanism of action of stellate ganglion block has generally been explained
      by vasodilation within its sphere of innervation. However, the success of
      treatment cannot always be explained by just one mechanism of action, because its
      clinical indications in Japan extend to many diseases, including systemic
      diseases. We propose a new mechanism of action for stellate ganglion block that
      is based on correction of melatonin rhythm disorder resulting from increased
      sympathetic nerve tone and does not involve vasodilation.

PMID- 12208187
TI  - Capsaicin pepper, cancer and ethnicity.
AB  - The 'hot' sensation produced by exposure to pepper is apparently due to two
      natural carcinogens: capsaicin in chili type peppers and safrole in black/white
      pepper. There are four cookeries in the United States that are noted for their
      high pepper content: Mexican-American, Cajun, white Creole, and black Creole.
      Each is largely confined to a single ethnic-cultural group which is concentrated
      in some counties. By use of county population and mortality data, significantly
      higher rates for stomach and liver cancer were found in counties inhabited by
      these four ethnic-cultural groups than in matched control counties. This involved
      both sexes. The cancer increase was dependent on the concentration of these
      groups in a county. These results strengthen and extend an earlier case-control
      study which found odds ratios above 5 for the stomach cancer association with
      capsaicin pepper. It is further evidence that capsaicin is a human carcinogen.

PMID- 12208188
TI  - Pneumoobstruction of the tracheobronchial tree as a hypothetical cause of
      balbuties.
AB  - The occurrence of balbuties is a common phenomenon. Balbuties is defined as
      frequent repetition and lengthening of syllables and words, alternatively
      frequent halting with pauses impairing the rhythmic flow of speech. Balbuties may
      have a negative influence upon the psychic as well as social development of an
      individual. Psychiatric co-morbidity of balbuties usually includes some other
      defects in behaviour, such as states of anxiety, depression, etc. The ethiology
      of balbuties has not yet been discovered, neither its casual therapy is possible.
      The phonating apparatus is formed by: the lungs with the trachea, the larynx, and
      the vocal tract. The source of the expired air flow is given by the expiring
      lungs. In balbuties the fatal defect probably results from a pneumoobstruction of
      the tracheobronchial tree in the peripheral respiratory passages. The present
      paper gives a hypothetical explanation of the cause.

PMID- 12208189
TI  - The suction mechanism as a factor in intrathoracic oedema, connective tissue or
      pleural effusion.
AB  - In pathological conditions, the negative intrapleural pressures (Ppl) may
      increase unequally. At some sites they may remain increased. We maintain that at
      these sites the increased pressures may lead to the production of oedema in the
      adjacent pleural walls and in adjacent pre-existing connective tissue, which may
      remain as oedema or may become connective tissue. Occasionally the increased
      negative Ppl may contribute to the production of pleural effusion. We term all
      these processes the suction mechanism (SM). This mechanism affords an
      interpretation of a series of images observed in chest X-rays. According to this
      view, lung shrinkage, narrowing of the pulmonary vessels and impairment of the
      lung function are not caused by the diffuse pleural fibrosis, but result from
      damage to the lung parenchyma. We also interpret the apical cap, the blunting of
      the costophrenic sulci, the broadening of the mediastinum and the retrosternal
      stripe in terms of the SM.

PMID- 12208190
TI  - Kushta(s): unique herbo-mineral preparations used in South Asian traditional
      medicine.
AB  - Herbs and minerals are the integral parts of traditional systems of medicine in
      many countries. Kushta is a form of herbo-mineral preparations used in
      traditional systems of medicine (Unani and Ayurvedic) of Indo-Pak subcontinent.
      These preparations have long been used and claimed to be the most effective and
      potent dosage form. However, there are only few scientific studies carried out on
      these products because of several reasons mainly being the lack of communication
      among traditional healers, physicians and scientists. The objective of this paper
      is to fill this gap by translating the old concepts in modern understanding,
      providing possible explanation and hypotheses. Some recommendations have also
      been given to provide the path to initiate research in this area of potential
      therapeutic value and public concern.

PMID- 12208191
TI  - Surgical repair of giant gastroduodenal perforation with Teflon-Felt?
AB  - Patients with longer duration of huge gastroduodenal perforation are known to be
      difficult to tolerate major surgery. Primary closure of the perforation will
      result in suture tension with high risk of dehiscence, gastric outlet
      obstruction, and even mortality. Teflon-Felt is a bioinert,
      polytetrafluoroethylene, flexible material used on patients with vascular defect.
      It is proposed that Teflon-Felt may be an optimal material for closure of giant
      gastroduodenal perforation to reduce suture tension without narrowing of the
      gastric outlet.

PMID- 12208192
TI  - The mathematical basis of sexual attraction.
AB  - Computer programs have been written to study the dynamic interaction in humans
      between environmental mutagenesis, the genomic load of deleterious mutations and
      the probability of zygote survival. The human genome is complex and highly
      redundant and as a consequence deleterious mutations accumulate. The computer
      programs are based on a model of the human genome in which deleterious mutations
      interact synergistically causing impaired performance in individual systems and
      this leads to a positive correlation between the total number of deleterious
      mutations in the genome and impaired performance across the whole spectrum of
      biological capability. This includes performance in intellectual tasks, sporting
      ability, the ability to fight disease and preserve health and the development of
      a symmetrical physical form. Sexual reproduction distributes deleterious
      mutations unequally amongst zygotes and the model predicts that zygote survival
      will correlate negatively with zygote mutational load. The computer simulation
      shows that rising environmental mutagenesis will lead to a rise in the human
      genomic mutational load and to decreased zygote survival, although the full
      effect would take several generations. If this occurred the health of future
      generations would suffer and methods to monitor environmental mutagenesis are
      required. The model also shows that a marked rise in environmental mutagenesis
      would lead to species extinction if mate choice were random, i.e., unrelated to
      the genomic mutational load. The biological imperfections caused by mutations,
      however, in health, intelligence and physical symmetry are all, to varying
      degrees, related to sexual attraction. The model shows that if mates are chosen
      in response to sexual attraction the species can be maintained in the presence of
      high environmental mutagenesis. A polygamous pattern in which females mate with a
      minority of males has the most marked effect in reducing the number of
      deleterious mutations in the next generation. The model also shows that as
      environmental mutagenesis falls the number of eligible males would increase and a
      species would change from a polygamous to a monogamous pattern of mating. These
      results imply that we are not attracted by good genes, but by a lack of bad
      genes. Sexual attraction is a force which counteracts genomic degradation.

PMID- 12208193
TI  - Thinking outside the synapse.
AB  - Bridging the gap between the parallel, distributed processing of groups of
      neurons and the serial, integrated processing of higher cognitive functions is a
      difficult hallenge. One possible mechanism originates in the shared space of the
      extracellular compartment. The opening and closing of ion channels in this space
      produce mechanical waves, presumably in the ultrasonic range. If the combined
      activities of enough channels produce strong enough waves, then integrated
      ultrasonic signals could broadcast information throughout the brain. If the
      broadcast signals are selectively received by target neurons, then several
      cognitive abilities readily emerge, including learning, memory, pattern
      recognition, and problem solving.

PMID- 12208194
TI  - Are the 'hard' martial arts, such as the Korean martial art, TaeKwon-Do, of
      benefit to senior citizens?
AB  - Falls are a leading cause of death in the elderly. Associated with aging is a
      loss of muscular strength, flexibility, and coordination. Regular exercise is
      widely believed to be of benefit for the elderly. To this end, various exercise
      regimes have been employed to battle the associated problems of aging. One such
      has been the Chinese martial art, Tai Chi Chuan (TC). TC as an exercise system
      uses slow smooth movements to train the body in balance, endurance, and strength.
      For this reason, it is known as a 'soft' martial art, in that it is very non
      impact oriented. There have been a variety of studies in the West examining the
      beneficial effects of TC. However, to date, there have been no studies with
      senior citizens using other martial arts, of which, TC is but one. The present
      study was designed to examine the appropriateness and effects of a Korean martial
      art known as TaeKwon-Do (TKD), a 'hard' martial art, on an elderly population
      measuring similar parameters reported for TC. Of those participants that attended
      >85% of classes, an increase was observed in the average number of push-ups,
      trunk flexion, and balance time on each foot. TKD proved effective at increasing
      one-leg balance in the population examined. Additionally, the overall dropout
      rate was extremely low suggesting both that the elderly are capable of
      participating in a hard martial art and that they have an interest in it as a
      viable alternative to other forms of exercise. The present study suggests that
      TKD as a form of exercise for an elderly population is both viable and
      potentially popular and warrants further study.

PMID- 12208195
TI  - Human breast cancer and lymphomas may share a common aetiology involving Mouse
      Mammary Tumour Virus (MMTV).
AB  - Mouse Mammary Tumour Virus (MMTV) causes breast tumours in mice, and has been
      implicated in the aetiology of murine lymphomas. Several recent human studies
      have detected MMTV-env DNA sequences in 30-40% of tumours from breast cancer
      patients but in less than 4% of normal breast tissue. MMTV DNA has been detected
      in simultaneously diagnosed primary lymphoma and breast cancer tissue, suggesting
      MMTV may be involved in the aetiology of both breast cancer and lymphoma. We
      further hypothesize that if lymphoma and breast cancer are both associated with a
      common aetiologic virus then women with prior lymphoma may have an increased risk
      of breast cancer and vice versa. Despite the significant increase in the
      incidence of both lymphoma and breast cancer over the last few decades, their
      aetiologies are not well understood. Intriguing evidence to date suggests that
      the aetiology of a subgroup of human breast cancers and lymphomas may have viral
      involvement, and this warrants further investigation.

PMID- 12208196
TI  - Adrenocorticotropic hormone in the aetiology and regression of neuroblastoma.
AB  - Neuroblastoma is predominantly a paediatric neoplasm of the sympathetic nervous
      system. Despite the aggressive nature of the disease, spontaneous regression is
      frequently observed in infants diagnosed under the age of 12 months; especially
      with a specific stage referred to as stage 4s. Discovering the conditions, the
      elements, the mechanism and the indices behind this regression phenomenon could
      have therapeutic potential for prevention and cure. A review of the literature
      has implicated adrenocorticotropin hormone in both the aetiology and spontaneous
      regression of neuroblastoma. Manipulation of adrenocorticotropin hormone may
      offer hope for prevention and cure. Ingestible products such as retinoic acid,
      glycyrrhizic acid, salsolinol and ketoconazole acting in concert, could represent
      instrumental tools in a therapeutic manipulation process.

PMID- 12208197
TI  - Clinical relevance of the sick role and secondary gain in the treatment of
      disability syndromes.
AB  - There are many controversial disability syndromes, representing medicolegal and
      social dilemmas for a variety of medical disciplines. Health care professionals
      are at a loss to cure these patients, and judges and disability review boards
      struggle to be fair while at the same time trying to understand the basis and
      appropriateness of the ever-growing claims of disability. Various models describe
      the illness behavior in these syndromes, and a recent model proposed that deals
      with the sick role, gain, and illness behavior in a social context is considered
      for its application to psychotherapy. One finds that despite the utility of such
      a model in describing the patient's behavior, using this knowledge to alter the
      behavior remains a difficult challenge for the psychotherapist.

PMID- 12208198
TI  - Go and chemoresistance of malignant cells.
AB  - In general terms the paper discusses the relevance of mitotically quiescent,
      malignant cells for increasing resistance to chemotherapy. Detailed are some
      routes to Go for malignancies either dependent or autonomous for their mitotic
      potential.

PMID- 12208199
TI  - Transformation of myeloid cells with atypical renewal.
AB  - The paper discusses malignant transformation of myeloid precursors that had
      atypical renewal in vivo. Their in vitro transformation rate disproportionates
      clinical incidences. Besides composition differences of transforming agents, this
      is due to quali-quantitative deficiencies of multitask growth factors added to
      empirical cultures. In combination these anomalies perturb the web of
      differentiation path, whose robustness minimizes clonal transformation in vivo.

PMID- 12208200
TI  - Percussion chemistry and muscle function.
AB  - A hypothesis is presented concerning the origin of the action of muscles in the
      human and animal bodies It is advanced that muscle action originates with very
      rapid chemical reactions known as percussion reactions. These give rise to the
      temporary precipitation of solids in muscle cells. The accompanying volume change
      gives rise to muscle contraction. The redissolving of these solids restarts the
      cycle. The percussion reaction also gives rise to percussion waves which travel
      along nerve fibres to cells in the brain and activate percussion reactions in the
      connected brain cells. The reverse also occurs and indicates the means whereby
      brain cells induce muscular action. It is shown that this mechanism is compatible
      with observations of muscle action.

PMID- 12208201
TI  - Schizophrenia and other mental disorders require long-term adoptive
      immunotherapy.
AB  - Many different microbial factors seem to contribute to the pathogenesis of
      schizophrenic and other psychiatric disorders. Activation of all T lymphocytes
      reactivates those downregulated by low-grade chronic infections and restores
      equilibrium in immune cell subpopulations. Different immune cell subpopulations
      express different neurotrophin receptors and produce different cytokines,
      particularly brain-derived neurotrophin (BDNF) and neurotrophin 3 (NT3) [M.
      Besser, R. Wank, J. Immunol. 162 (1998) 6303-6306] that appear to play a key role
      in schizophrenic and bipolar disorders [E. Jonsson, S. Brene, X.R. Zhang, et al.,
      Acta Psychiatr. Scand. 95 (1997) 414-419; R.S. Duman, Arch. Gen. Psychiatry 54
      (1997) 597-606; J.A. Siuciak, D.R. Lewis, S.J. Wiegand, R.M. Lindsay, Pharmacol.
      Biochem. Be 56 (1997) 131-137]. The hypothesis that adoptive immunotherapy is
      effective in psychiatric disorders will be supported by three case reports, in a
      patient with bipolar disorder, a patient with schizophrenia, and a patient with
      autism.

PMID- 12208202
TI  - Impaired inactivation of digestive proteases by deconjugated bilirubin: the
      possible mechanism for inflammatory bowel disease.
AB  - Inflammatory bowel disease refers to ulcerative colitis and Crohn's disease, two
      gut diseases with unknown causes. The dramatic increase in the last half century
      and the big difference in incidence for people with the same ethnic background
      but living in different areas strongly suggested that environmental factors
      played the dominant role for these diseases. The similarity in many aspects for
      these two diseases suggested a common causative factor. Here I suggest the
      impaired inactivation of digestive proteases by deconjugated bilirubin, as the
      result of the inhibition of bilirubin deconjugation enzyme, beta-glucuronidase,
      originated from the luminal bacteria and mucosa of the gut, to be a possible
      mechanism for both ulcerative colitis and Crohn's diseases. I also provide
      evidence to suggest that saccharin could be the causative or one of the most
      important risk factors for inflammatory bowel disease as for its inhibition on
      beta-glucuronidase in the intestine.

PMID- 12208203
TI  - Centuries ago scholars had knowledge about inheritance of psychiatric disorders
      and behavioral traits.
AB  - The author presents evidence that a genetic contribution to the development of
      psychiatric disorders and behavioral traits has been appreciated for many
      centuries. The author suggests that people had knowledge about inheritance of
      behavioral features and psychiatric illnesses centuries ago. Physicians all
      through the ages have confronted similar psychiatric problems, and their struggle
      to understand, classify, and treat such afflictions may have begun earlier than
      commonly believed.

PMID- 12208204
TI  - Etiopathogenesis of depression in patients with alcoholism: role of changes in
      thyroid function.
AB  - Alcoholism poses a significant risk for the development of depression. Alcohol
      abuse and dependence significantly affect thyroid function. Considerable evidence
      suggests that minor changes in thyroid function may affect mood and behavior. The
      author suggests that alcohol-induced changes in thyroid function may contribute
      the development of depression in patients with alcoholism. Probably, alcohol
      induced alterations in thyroid function are not a sufficient cause of depression.
      Most likely, they work in concert with inherited, acquired, and environmental
      risk factors. Alcohol may be particularly damaging to the impaired thyroid gland.
      Studies of the interrelationships between alcoholism and depression may help
      elucidate the causes of both.

PMID- 12208205
TI  - Intragenomic conflict and cancer.
AB  - Intragenomic conflict occurs when some elements within the genome produce effects
      that enhance their own probability of replication or transmission at the expense
      of other elements within the same genome. Here it is proposed that mutations
      involved in intragenomic conflict are particularly likely to be co-opted by
      evolving lineages of cancer cells, and hence should be associated with the
      occurrence of cancer. We discuss several types of intragenomic conflict that are
      associated with various forms of cancer.

PMID- 12208206
TI  - The intromission function of the foreskin.
AB  - Masters and Johnson observed that the foreskin unrolled with intercourse.
      However, they overlooked a prior observation that intromission was thereby made
      easier. To evaluate this observation an artificial introitus was mounted on a
      scales. Repeated measurements showed a 10-fold reduction of force on entry with
      an initially unretracted foreskin as compared to entry with a retracted foreskin.
      For the foreskin to reduce the force required it must cover most of the glans
      when the penis is erect. This may occur only in humans. These observations mean
      that foreskin and prepuce can no longer be considered synonymous. Why the penises
      of humans and chimpanzees evolved so differently should be addressed in light of
      these findings.

PMID- 12208207
TI  - Hypophosphatemic osteomalacia in neurofibromatosis 1: hypotheses for pathogenesis
      and higher incidence of spinal deformity.
AB  - Osteomalacia is rarely encountered in association with neurofibromatosis 1,
      characterized by phosphate loss in the urine and its pathogenesis is still
      unknown. Incidence of spinal deformities in cases of neurofibromatosis 1
      associated with osteomalacia seems to be high. Spinal deformities are unlikely to
      be due to osteomalacia itself. Melatonin deficiency was proposed to be present in
      cases of neurofibromatosis 1 and to be an operating factor in progression of
      spinal deformities. We might hypothesize that putative melatonin deficiency in
      cases of neurofibromatosis 1 might play a role in the pathogenesis of
      hyperphosphaturea by decreasing sodium-phosphate cotransport, increasing the
      level of cAMP, the un-antagonized effect of dopamine on phosphate reabsorption
      and increasing glucocorticoid levels. Parathyroid overactivity that may occur
      secondary to osteomalacia might have synergistic effects with dopamine and
      further exaggerate phosphate loss in urine. On the other hand, excess
      corticosteroid secretion would decrease nocturnal melatonin level. Moreover, in
      the presence of hypophosphatemia, hypercortisolism might further inhibit
      melatonin secretion that might lead to progression of spinal deformities in these
      cases.

PMID- 12208208
TI  - Is there a "bladder sex"? The relation of different sex hormones and sex hormone
      receptors in bladder in childhood.
AB  - The aim of this study was to review the classical concept of bladder physiology
      in regard to sex hormone effects and to focus on a new concept. Sex hormones
      affect bladder functions and the classical concept tries to explain these effects
      via alpha and beta adrenoreceptors. The effects of hormones had been investigated
      in this understanding. To obtain a biological response to steroids in target
      tissues, specific proteins--so-called receptors--are warranted. After the
      demonstration of the sex hormone receptors in bladder first in adults and in
      children urge questioning the effects of hormones in this regard. The hypothesis
      is based on the fact that, if a special receptor is present, the direct (via sex
      hormone receptors) effect is more likely to occur as an indirect effect (via
      alpha and beta adrenoreceptors). There is evidence that there is a sex difference
      and the sex receptors and hormones play an important role in some bladder
      disorders. Therefore we stress the importance of investigating especially the
      pediatric patients with bladder problems in regard to sex hormone receptors and
      hormonal status.

PMID- 12208209
TI  - Proposition of a new system of medicine based on tolerance principle.
AB  - The author proposes an explanatory model to modify Hahnemann's old tool--"similia
      similibus curantur"--and suggested a new experimental design to be used to detect
      the root cause of several chronic diseases and to treat them. All the biochemical
      reactions of an ideal cell are interlinked by enzymes like a network and
      shortfall of any one of them may create specific combination of symptoms (e.g.,
      phenylketonuria, alkaptonuria, etc.), due to lack of one or more products that
      enables us to identify the responsible enzyme. Sometimes malsynthesis of an
      unknown enzyme(s) or receptors are responsible for a chronic disease and it
      becomes difficult to identify them by merely observing symptoms. Hence
      involvement of a normal healthy person ("prover") would be essential to detect
      it. If an inhibitor that comes from a drug is able to bring the same combination
      of symptoms in prover it may be predicted that the drug is able to bind and
      inhibit the responsible enzyme or its product. Minute doses of the same
      inhibitor(s) can cure the disease if it can act as the ligand of the same
      enzyme(s), by increasing the rate of transcription (by a positive feedback loop),
      to compensate the loss of product of the same. The ligand-inhibitor should be
      trapped in by an organic molecule, like ethanol by the process of potentization
      to increase the invasiveness of the medicine and to avoid detoxification
      mechanism, baffling of which increases the concentration of inhibitor inside the
      cell in course. The cells able to cope up with the stress by the operation of
      positive feedback loop or compensation cycle synthesize more enzymes and multiply
      rapidly, but those cells unable to tolerate such stress gradually perish. Thus
      Hahnemann's principle being dependent on the cause of symptoms becomes modified
      as "similia similibus curantur causosymptomically".

PMID- 12208210
TI  - Why can't Chinese Han drink alcohol? Hepatitis B virus infection and the
      evolution of acetaldehyde dehydrogenase deficiency.
AB  - An aldehyde-dehydrogenase (ALDH2) deficiency is a biological curb on excess
      alcohol-drinking. This enzyme deficiency is very common amongst Oriental people
      while it is relatively rare for most other populations. We observe that there is
      good geographical correlation between the prevalence of the mutant ALDH2*2
      alleles and hepatitis B virus (HBV) infections. Populations that demonstrate a
      high ALDH2*2 prevalence are all located in HBV-endemic areas. Further, studies
      have shown that HBV and alcohol drinking exhibit a synergistic effect upon liver
      cirrhosis and cancer. A shorter life span for those with HBV infection and heavy
      alcohol consumption may result in a selection of the ALDH2*2 gene. We postulate
      that there may be patterns of evolutionary adaptation for ALDH2 deficiency in
      certain HBV-endemic areas and that these adaptations can produce differences in
      human alcohol-drinking capability.

PMID- 12208211
TI  - Relationship of senescence of pulmonary system to chronic obstructive pulmonary
      disease in the advanced life.
AB  - Chronic obstructive pulmonary disease (COPD) is a major worldwide health problem.
      There exists a relationship between COPD and increased oxidative stress, and
      oxidants may be involved in lung damage during the course of COPD.
      Polymorphonuclear (PMN) cell recruitment at lung level plays an important role in
      free radical overproduction, impact inflammatory processes and may alter oxidant
      antioxidant balance. Biological aging is thought to be influenced by free radical
      generation, aging, and the diseases. All the components of the respiratory system
      are affected by aging. Nutrition, smoking habits and sleep-related disorders also
      affect the respiratory system. Whether these changes are due to aging or
      associated with aging is a matter of debate. Since alterations caused by aging
      and cigarette smoke in lungs of various species were informed to be partly
      simulated with age-related alterations in human lung, the effects of oxidative
      agents and antioxidative parameters on both COPD and aging were evaluated.

PMID- 12208212
TI  - ELF-EMF, endocrine disruptors, light: what if we apply triage to research?
AB  - Triage in medicine is an effective means to maximize health benefits of limited
      resources. This paper suggests to use triage principles as a means to identify
      biomedical and epidemiological research priorities. The author applies the
      following questions to three putative problems which receive different research
      and funding attention: (a) Does a suspected exposure render many humans at risk?
      (b) Is a disease frequent, difficult to treat and expensive? and (c) Is a causal
      link between (a) and (b) biologically plausible? On the basis of answers to (a),
      (b), and (c) it is concluded that ELF-EMF and childhood leukaemia would not
      qualify for further urgent investigations and that endocrine disruptors and to-be
      identified end-points would not qualify for urgent investigations. Provided that
      answers to the outlined triage questions can be considered as a practical guide
      to urgent research investigations, the suggestive link between light, endocrine
      systems and hormone-dependent cancers should become a higher priority research
      focus.

PMID- 12208213
TI  - Preventive research and interventive research: in favour of to act rather than to
      react.
AB  - Conventional wisdom knows that "prevention is better than cure". However, in the
      many cases where we do not understand how to cure or intervent, prevention is not
      only better but may be the only way to promote public health. As the principal
      basis for preventive action, this paper advocates to focus more on preventive
      rather than on interventive research. Preventive research, as defined here, aims
      to identify a determinant A in the environment which causes an undesirable health
      effect B in the human body. Preventive research ends when the critical nature of
      A is convincingly established and ways to avoid A are identified. Interventive
      research, as defined here, aims to understand and manipulate the chain from A to
      B within the human body. Examples of real (poliomyelitis, lung cancer, AIDS) and
      possible scourges (BSE) from the last and this century indicate that preventive
      research has delivered culprits but that interventive research could not-and
      likely will not-unravel the whole chain from A to B. Based also on conceptual
      considerations it is concluded that, while both research approaches are needed, a
      strategy with more emphasis on preventive research and taking action at an
      earlier stage may lead to more community success.

PMID- 12208214
TI  - Are sildenafil and theophylline effective in the prevention of high-altitude
      pulmonary edema?
AB  - High-altitude pulmonary edema reflects a potentially life-threatening condition
      affecting susceptible persons in the second night after ascent to altitudes above
      2500 m. Currently, nifedipine is the only pharmacological intervention approved
      for both, prevention and treatment of high-altitude pulmonary edema. We evaluated
      the application of the phosphodiesterase-V inhibitor sildenafil combined with the
      non-selective phosphodiesterase-inhibitor theophylline as preventive agents. In
      theory, the proposed regimen can impede the two main pathophysiological features
      of high-altitude pulmonary edema: the deleteriously high pulmonary artery
      pressure (sildenafil's task) on the one hand, and the activation of an
      inflammatory cascade (theophylline's task) on the other hand. We suggest that
      these orally applicable phosphodiesterase inhibitors might be useful in the
      prevention of high-altitude pulmonary edema.

PMID- 12208215
TI  - Positive inotropy for acute heart failure complicating myocardial infarction.

PMID- 12208216
TI  - More histological information in acute coronary death.

PMID- 12208217
TI  - 'I can see clearly now': a new view on the use of IV GP IIb/IIIa inhibitors in
      acute coronary syndromes.

PMID- 12208218
TI  - Percutaneous coronary intervention in diabetics with prior coronary artery bypass
      surgery: sweet or sour?

PMID- 12208219
TI  - Management of atrial fibrillation in patients with implantable cardioverter
      defibrillator. Do all need a dual chamber device?

PMID- 12208220
TI  - Percutaneous valve implantation: back to the future?

PMID- 12208221
TI  - Should early elective surgery be performed in patients with severe but
      asymptomatic aortic stenosis?

PMID- 12208222
TI  - Safety and efficacy of a novel calcium sensitizer, levosimendan, in patients with
      left ventricular failure due to an acute myocardial infarction. A randomized,
      placebo-controlled, double-blind study (RUSSLAN).
AB  - AIMS: To evaluate the safety and efficacy of levosimendan in patients with left
      ventricular failure complicating acute myocardial infarction. METHODS AND
      RESULTS: Levosimendan at different doses (0.1-0.4 microg x kg(-1) x min(-1)) or
      placebo were administered intravenously for 6h to 504 patients in a randomised,
      placebo-controlled, double-blind study. The primary end-point was hypotension or
      myocardial ischaemia of clinical significance adjudicated by an independent
      Safety Committee. Secondary end-points included risk of death and worsening heart
      failure, symptoms of heart failure and all-cause mortality. The incidence of
      ischaemia and/or hypotension was similar in all treatment groups (P=0.319). A
      higher frequency of ischaemia and/or hypotension was only seen in the highest
      levosimendan dose group. Levosimendan-treated patients experienced lower risk of
      death and worsening heart failure than patients receiving placebo, during both
      the 6h infusion (2.0% vs 5.9%; P=0.033) and over 24h (4.0% vs 8.8%; P=0.044).
      Mortality was lower with levosimendan compared with placebo at 14 days (11.7% vs
      19.6%; hazard ratio 0.56 [95% CI 0.33-0.95];P =0.031) and the reduction was
      maintained at the 180-day retrospective follow-up (22.6% vs 31.4%; 0.67 [0.45
      1.00],P =0.053). CONCLUSION: s Levosimendan at doses 0.1-0.2 microg x kg(-1) x
      min(-1) did not induce hypotension or ischaemia and reduced the risk of worsening
      heart failure and death in patients with left ventricular failure complicating
      acute myocardial infarction.

PMID- 12208223
TI  - Sudden unexpected death in young adults. Discrepancies between initiation of
      acute plaque complications and the onset of acute coronary death.
AB  - AIMS: To study the time relationship between the onset of coronary thrombosis and
      sudden unexpected cardiac death in young adults. METHODS AND RESULTS: Hearts of
      11 young adults (< or = 35 years), who had died within 1h after onset of symptoms
      and presented with a coronary thrombotic occlusion were studied retrospectively
      for the type of underlying plaque complication and the time of onset of thrombus
      formation. In all cases tissue blocks were taken from the occluded artery and
      sectioned for microscopic evaluation. Of 11 culprit lesions 10 were mainly
      fibrocellular; only one was lipid-rich. Inflammatory cells were found in all
      plaques, albeit in highly variable amounts. Plaque erosion had occurred in nine;
      deep ruptures in two. Analysis of the plaque-related occluding thrombus revealed
      fresh thrombosis in three (both ruptured plaques and one erosion); the other
      eight, however, showed occlusion with different histological stages of
      organization of thrombus. CONCLUSIONS: Despite strict inclusion criteria for
      sudden death in these young adults, the majority must have had plaque instability
      for some time, since thrombus formation had occurred at least days to weeks prior
      to the acute event.

PMID- 12208224
TI  - Platelet glycoprotein IIb/IIIa inhibition in acute coronary syndromes. Gradient
      of benefit related to the revascularization strategy.
AB  - AIMS: To assess the efficacy of platelet glycoprotein IIb/IIIa inhibitors in
      patients with acute coronary syndromes primarily medically managed. METHODS AND
      RESULTS: We performed a meta-analysis of the randomized clinical trials of
      platelet glycoprotein IIb/IIIa inhibitor therapy in the medical management of non
      ST-elevation acute coronary syndromes. Among 29570 patients, IIb/IIIa integrin
      blockade was associated with a reduction in death or non-fatal myocardial
      infarction at 30 days, from 11.5% to 10.7% (odds ratio 0.91,P =0.02). Patients
      undergoing percutaneous coronary intervention during index hospitalization
      sustained a greater reduction in ischaemic events (odds ratio 0.82, P=0.01) than
      patients medically managed (odds ratio 0.95, P=0.27). Among patients undergoing
      intervention, the benefit was more pronounced if the procedure was performed
      during glycoprotein IIb/IIIa inhibitor infusion (odds ratio 0.74; P=0.02), than
      if revascularization was performed after drug discontinuation (odds ratio 0.87,P
      =0.17). CONCLUSION: This analysis, including the entire large-scale trial
      experience of intravenous glycoprotein IIb/IIIa inhibitors in patients with acute
      coronary syndromes primarily medically managed, demonstrates an overall
      significant, albeit moderate, reduction in 30-day death or myocardial infarction
      associated with therapy. Although not based on a prospectively defined
      hypothesis, the findings suggest a gradient of benefit conferred by these agents
      depending on the revascularization strategy used.

PMID- 12208225
TI  - Slowed ST segment recovery despite early infarct artery patency in patients with
      Q waves at presentation with a first acute myocardial infarction. Implications of
      initial Q waves on myocyte reperfusion.
AB  - BACKGROUND: The presence of Q waves at presentation with a first acute myocardial
      infarction reflects a more advanced stage of the infarction process. When infarct
      related artery patency (Thrombolysis in Myocardial Infarction 2 or 3 flow) is
      restored, resolution of ST segment elevation indicating successful myocyte
      reperfusion may differ according to how far the infarction process has
      progressed. METHODS AND RESULTS: In 144 patients with a first acute myocardial
      infarction treated with streptokinase in the first Hirulog Early Reperfusion
      Occlusion trial, information was obtained from continuous ST segment monitoring,
      the presenting electrocardiogram and early angiography performed at a median time
      of 99 min after the commencement of streptokinase (interquartile range 89-108
      min). We determined how many patients had 50% ST recovery within 120 min and in
      how many cases it was sustained over 4h. In the 109 patients with patent infarct
      related arteries, 50% ST recovery occurred in 95% of patients without vs 80% of
      those with initial Q waves (P=0.03), and sustained ST recovery occurred in 67% of
      patients without vs 47% of those with initial Q waves (P=0.03). On multivariate
      analysis including the time from symptom onset to streptokinase therapy, the
      presence of Q waves at presentation was the only predictor of failure to achieve
      50% ST recovery (odds ratio 5.08, 95% confidence interval 1.29-20.01, P=0.02).
      TIMI 2 flow, as opposed to TIMI 3 flow, was the only predictor of failure to
      achieve stable ST recovery (odds ratio 2.63, 95% confidence interval 1.15-5.88,P
      =0.02). CONCLUSION: The presence of initial Q waves predicts slower and less
      complete ST recovery, reflecting reduced myocyte reperfusion, even in those with
      early infarct artery patency. These patients may be targeted for new therapeutic
      strategies to improve microvascular reperfusion.

PMID- 12208226
TI  - Comparative outcomes of percutaneous coronary interventions in diabetics vs non
      diabetics with prior coronary artery bypass grafting.
AB  - AIMS: To determine the influence of diabetes on outcome after percutaneous
      coronary intervention in patients with prior coronary artery bypass grafting.
      METHODS AND RESULTS: Patients with prior coronary artery bypass grafting
      undergoing percutaneous coronary intervention from 1 January 1996, to 31 August
      2000, were divided into two groups based on whether or not they had diabetes,
      excluding patients with acute infarction or shock. Cox proportional hazards
      models were utilized to estimate the association between diabetes and adverse
      events. One thousand one hundred and fifty-three post-coronary artery bypass
      grafting percutaneous coronary intervention patients were identified (326
      diabetics and 827 non-diabetics). Diabetics were younger, more likely to have
      hypertension, heart failure, and lower ejection fraction. Procedural
      characteristics and angiographic and procedural success rates were similar.
      Diabetes was associated with increased mortality (hazard ratio 1.58, 95%
      confidence intervals 1.10-2.27). Diabetes did not have a significant effect on
      mortality in patients treated for single-territory coronary disease (hazard ratio
      1.44, 95% confidence intervals 0.69-3.02), but did in patients with multi
      territory disease (hazard ratio 1.79, 95% confidence intervals 1.16-2.76).
      However, in diabetics with multi-territory disease who were completely
      revascularized with percutaneous coronary intervention, mortality was comparable
      to non-diabetics (hazard ratio 1.32, 95% confidence intervals 0.57-3.03).
      CONCLUSION: Among percutaneous coronary intervention patients with prior coronary
      artery bypass grafting, diabetes portends an adverse prognosis.

PMID- 12208227
TI  - Treatment of superior vena cava obstruction secondary to pacemaker wires with
      balloon venoplasty and insertion of metallic stents.
AB  - AIMS: Pacemaker wires can result in stenosis of the superior vena cava and other
      central veins. The aim of this study is to demonstrate the safety and
      effectiveness of treating stenoses of the superior vena cava (SVC) and central
      veins with balloon venoplasty and metallic stent insertion in the presence of
      cardiac pacemaker wires. METHODS AND RESULTS: Three patients were referred to the
      department after developing symptomatic SVC obstruction following implantation of
      a cardiac pacemaker several years earlier. They were examined with duplex
      ultrasound and venography, which revealed significant stenoses of the central
      veins. These patients subsequently underwent endovascular treatment which
      involved balloon dilation and stent insertion. The treatment was successful in
      all three patients, without any complications. Long-term patency of up to 4 years
      is recorded. No pacemaker function dysfunction was encountered. CONCLUSION: SVC
      stenting is safe and effective in patients who develop the SVC obstruction after
      cardiac pacemaker insertion.

PMID- 12208228
TI  - Efficacy of a dual chamber defibrillator with atrial antitachycardia functions in
      treating spontaneous atrial tachyarrhythmias in patients with life-threatening
      ventricular tachyarrhythmias.
AB  - BACKGROUND: Atrial fibrillation has a high incidence in patients wearing an
      implantable cardioverter defibrillator for ventricular tachyarrhythmias and may
      lead to palpitations, heart failure, angina, stroke and inappropriate
      defibrillator discharge. The aim of the study was to evaluate the efficacy of a
      dual chamber defibrillator with atrial antitachycardia functions in treating
      spontaneous atrial tachyarrhythmias. METHODS: One hundred and twelve patients, 88
      male, mean age 64+/-11 years, were enrolled. Seventy-six had ischaemic heart
      disease, 21 idiopathic dilated cardiomyopathy, nine other heart diseases, six no
      structural heart disease. The mean left ventricular ejection fraction was 40+/
      11%. Sixty-two had prior atrial tachyarrhythmias. RESULTS: Follow-up lasted 11+/
      9 months (range 1-42). Among 933 ventricular tachyarrhythmia episodes, 100% of
      ventricular fibrillation and 92% of ventricular tachycardia were successfully
      cardioverted. Among 414 detected sustained atrial tachyarrhythmias, 195 were
      classified as atrial tachycardia (47.1%), 192 as atrial fibrillation (46.4%) and
      27 (6.5%) as sinus rhythm. The detection-positive predictive value was 93.5%.
      Therapy success rates: antitachy pacing on atrial tachycardia = 71.3% (crude
      estimate); 66.1% (adjusted estimate); 50 Hertz on atrial fibrillation=36.2%
      (crude estimate); 13.5% (adjusted estimate); atrial shock on atrial fibrillation
      = 62.5% (mean energy 7.8+/-14.1J). Shock efficacy was 32% when delivered energy
      was < or = 2 atrial defibrillation threshold at implant and 92% when >2. Duration
      of successfully treated atrial episodes was significantly lower than that of
      unsuccessfully treated (6+/-26 min vs 42+/-60). CONCLUSIONS: Atrial antitachy
      pacing and shock therapies demonstrated very high efficacy in treating atrial
      tachyarrhythmias in defibrillator patients.

PMID- 12208229
TI  - Does 'more' mean maximal therapy.

PMID- 12208231
TI  - Desynchronising effect of the endothelium on intracellular Ca2+ concentration
      dynamics in vascular smooth muscle cells of rat mesenteric arteries.
AB  - The kinetics of the intracellular Ca2+ concentration ([Ca2+]i) of vascular smooth
      muscle cells (VSMCs) in rat small mesenteric arteries was investigated by
      confocal laser scanning microscopy using the fluorescent Ca2+ indicator fluo-3
      AM. One micromole noradrenaline (NA) induced randomly distributed transient
      elevations of [Ca2+]i in several single VSMCs which were weakly temporally
      coupled. Higher NA concentrations of 3 or 10 microM, however, induced strongly
      synchronised [Ca2+]i oscillations in VSMCs. In preparations with intact
      endothelium, the synchronisation of [Ca2+]i signals was attenuated by
      acetylcholine (ACh) but augmented by the NO synthase antagonist L-NAME, pointing
      to a desynchronising effect of the endothelium even under basal conditions. In
      preparations with or without intact endothelium sodium nitroprusside (SNP) as
      well as the gap-junction uncoupler heptanol reversibly desynchronised the [Ca2+]i
      transients. The effect of ACh but not that of SNP was influenced by L-NAME.
      Propagated intracellular [Ca2+]i waves had a velocity of 25 microm/s. The phase
      shift of [Ca2+]i oscillations between single VSMCs were maximally 2s and
      independent of the distance of up to 90 microm between individual cells.
      Therefore, we consider intercellular [Ca2+]i waves to be too slow to account for
      the synchronisation of [Ca2+]i oscillations. We conclude that the coupling of
      [Ca2+]i signals in vascular smooth muscle cells is not constant but highly
      regulated by NA and by endothelium derived NO. Oscillations of vessel contraction
      at high sympathetic tone may be induced by synchronisation of [Ca2+]i transients
      of distinct VSMCs whereas endothelium derived NO inhibits vasomotion by
      desynchronising [Ca2+]i transients of single VSMCs.

PMID- 12208232
TI  - Role of mitochondria in intracellular calcium signaling in primary and secondary
      sensory neurones of rats.
AB  - The participation of different calcium-regulated mechanisms in the generation of
      cytosolic Ca(2+) transients during neuronal excitation has been compared in
      isolated large and small primary (dorsal root ganglia (DRG)) and secondary
      (spinal dorsal horn (DH)) rat sensory neurones. As it was shown before in murine
      primary sensory neurones the application of mitochondrial protonophore CCCP by
      itself induced only small elevation of [Ca(2+)](i). However, its preceding
      application substantially increased the peak amplitude of depolarization-induced
      transients. Application of CCCP immediately after termination of the depolarizing
      pulse induced in both types of primary neurones a massive release of Ca(2+) from
      mitochondria into the cytosol. In secondary neurones application of CCCP by
      itself induced a substantial release of Ca(2+) from the mitochondria, but its
      preceding application resulted in only an insignificant increase in the peak
      amplitude of depolarization-triggered calcium transients. Application of CCCP
      immediately after termination of depolarization elicited a small release of
      Ca(2+), which became more pronounced when the application was delayed. Preceding
      application of CCCP increased the amplitude of the transients induced by caffeine
      triggered Ca(2+) release from the endoplasmic reticulum in secondary neurones and
      did not affect those in large primary neurones. These findings may be explained
      by substantial differences in the density and distribution of mitochondria in the
      cytosol of primary and secondary sensory neurones. This suggestion was confirmed
      electronmicroscopically, showing a much lower density of mitochondria near
      plasmalemma in secondary sensory neurones and predominant clustered location of
      mitochondria beneath the plasmalemma in the primary cells. The possible
      functional importance of these differences is discussed.

PMID- 12208233
TI  - Expression of Ca2+-ATPase and Na+/Ca2+-exchanger is upregulated during epithelial
      Ca2+ transport in hypodermal cells of the isopod Porcellio scaber.
AB  - It is thought that a plasma membrane Ca(2+)-transport ATPase (PMCA) and a
      Na(+)/Ca(2+)-exchange (NCE) mechanism are involved in epithelial Ca(2+) transport
      (ECT) in a variety of crustacean epithelia. The sternal epithelium of the
      terrestrial isopod Porcellio scaber was used as a model for the analysis of
      Ca(2+)-extrusion mechanisms in the hypodermal epithelium. Using RT-PCR, we
      amplified a cDNA fragment of 1173 bp that encodes a protein sequence possessing
      72% identity to the PMCA from Drosophila melanogaster and a cDNA fragment of 791
      bp encoding a protein sequence with 50% identity to the NCE from Loligo
      opalescens. Semiquantitative RT-PCR revealed that the expression of both mRNAs
      increases from the non-Ca(2+)-transporting condition to the stages of CaCO(3)
      deposit formation and degradation. During Ca(2+)-transporting stages, the
      expression of PMCA and NCE was larger in the anterior sternal epithelium (ASE)
      than in the posterior sternal epithelium (PSE). The results demonstrate for the
      first time the expression of a PMCA and a NCE in the hypodermal epithelium of a
      crustacean and indicate a contribution of these transport mechanisms in ECT.

PMID- 12208234
TI  - Mutations in the RYR1 gene in Italian patients at risk for malignant
      hyperthermia: evidence for a cluster of novel mutations in the C-terminal region.
AB  - Mutations in the ryanodine receptor type 1 (RYR1) gene are associated with
      Malignant Hyperthermia (MH) and Central Core Disease (CCD). We report here on the
      molecular analysis of the RYR1 gene in Italian families referred as potential
      cases of MH or in patients with CCD or multicore/minicore myopathy. Of a total of
      20 individuals with mutations in the RYR1 gene, 14 were part of a group of 47 MH
      susceptible (MHS) patients, 4 of 34 individuals diagnosed as MH equivocal (MHE),
      and 2 were patients diagnosed with minicore myopathy and CCD, respectively.
      Mutations were found to segregate with the MHS or MHE phenotype within the
      families of the probands. A discordance between phenotype and genotype was
      observed in a family where a mutation detected in an MHS proband was also found
      in the father who had been diagnosed MH normal (MHN) at the IVCT. In addition to
      known mutations, seven novel mutations were found, five of which occurred in
      exons encoding the C-terminal region of RYR1. These results indicate that the C
      terminal region of RYR1 represents an additional hot spot for mutations in
      patients with MH, similar to what has been reported for patients with CCD.

PMID- 12208235
TI  - Comparison of the effect of ATP on intracellular calcium ion dynamics between rat
      testicular and cerebral arteriole smooth muscle cells.
AB  - Adenosine 5'-triphosphate (ATP), when released from neuronal and non-neuronal
      tissues, interacts with cell surface receptors produces a broad range of
      physiological responses. The goal of the present study was to examine the issue
      of whether vascular smooth muscle cells respond to ATP. To this end, the dynamics
      of the intracellular concentration of calcium ions ([Ca(2+)](i)) in smooth muscle
      cells in testicular and cerebral arterioles was examined by laser scanning
      confocal microscopy. ATP produced an increase in [Ca(2+)](i) in arteriole smooth
      muscle cells. While P1 purinoceptor agonists had no effect on this process, P2
      purinoceptor agonists induced a [Ca(2+)](i) increase and a P2 purinoceptor
      antagonist, suramin, completely inhibited ATP-induced [Ca(2+)](i) dynamics in
      both arteriole smooth muscle cells. In testicular arterioles, Ca(2+) channel
      blockers and the removal of extracellular Ca(2+), but not thapsigargin
      pretreatment, abolished the ATP-induced [Ca(2+)](i) dynamics. In contrast, Ca(2+)
      channel blockers and the removal of extracellular Ca(2+) did not completely
      inhibit ATP-induced [Ca(2+)](i) dynamics in cerebral arterioles. Uridine 5'
      triphosphate caused an increase in [Ca(2+)](i) only in cerebral arterioles and
      alpha,beta-methylene ATP caused an increase in [Ca(2+)](i) in both testicular and
      cerebral arterioles. We conclude that testicular arteriole smooth muscle cells
      respond to extracellular ATP via P2X purinoceptors and that cerebral arteriole
      smooth muscle cells respond via P2X and P2Y purinoceptors.

PMID- 12208236
TI  - Messenger RNA decay during aging and development.
AB  - Gene expression is a combination of many processes, including transcription, pre
      mRNA processing, nucleocytoplasmic transport of mRNA, translation, mRNA decay,
      and protein modification and decay. Many changes in the programs of gene
      expression occur during development, differentiation, and aging. These
      alterations are reflected at both the mRNA and protein levels. While altered gene
      expression at the levels of transcription and protein turnover has been
      appreciated for some time, mRNA decay is now emerging as an important control
      point and a major contributor to gene expression as well. Continuing
      identification of the protein factors and cofactors, and mRNA instability
      elements, responsible for mRNA decay are allowing us to build a comprehensive
      picture of the highly orchestrated processes involved in mRNA decay and its
      regulation. Here, I survey mRNA decay processes in eukaryotes and describe some
      molecular mechanisms that alter the decay rates of specific mRNAs, leading to
      major changes in gene expression during development and aging.

PMID- 12208237
TI  - Longevity, mortality and body weight.
AB  - The purpose of this study was to analyze the relation of total body weight to
      longevity and mortality. The MEDLINE database was searched for data that allow
      analysis of the relationship between absolute body weight and longevity or
      mortality. Additional data were used involving US veterans and baseball players.
      Trend lines of age at death versus body weight are presented. Findings show
      absolute body size is negatively related to longevity and life expectancy and
      positively to mortality. Trend lines show an average age at death versus weight
      slope of -0.4 years/kg. We also found that gender differences in longevity may be
      due to differences in body size. Animal research is consistent with the findings
      presented. Biological mechanisms are also presented to explain why increased body
      mass may reduce longevity. Life expectancy has increased dramatically through
      improved public health measures and medical care and reduced malnutrition.
      However, overnourishment and increased body size have promoted an epidemic of
      chronic disease and reduced our potential longevity. In addition, both excess
      lean body mass and fat mass may promote chronic disease.

PMID- 12208238
TI  - Translational fidelity, protein oxidation, and senescence: lessons from bacteria.
AB  - Senescence of growth-arrested Escherichia coli cells is like mandatory aging in
      higher eukaryotes, accompanied by increased oxidative modifications of
      macromolecules. Similar to aged flies, this senescence-related oxidation targets
      enzymes of the Krebs cycle. Additional targets include the universal stress
      protein A, the Hsp70 chaperone DnaK, translation elongation factors, and histone
      like proteins. However, during the early stages of stasis, protein oxidation is
      more general and affects a large number of proteins. Attempts to correlate this
      protein oxidation with a reduced activity of the antioxidant defense systems or
      an increased tendency of the respiratory apparatus to produce reactive oxygen
      species (ROS) have generated conflicting results. Instead, recent data indicate
      that oxidation of proteins may occur in the absence of an increased oxidative
      stress and is rather caused by an increased production of substrates available
      for oxidative attack. Misfolded and aberrant proteins appear to be such
      substrates and the production of aberrant polypeptides surge during the early
      stages of stasis due to a reduced translational fidelity. The data point to a
      novel mechanism involved in protein oxidation that has not been considered
      previously in aging research.

PMID- 12208239
TI  - UV-light-induced signal cascades and skin aging.
AB  - UV irradiation acts as a broad activator of cell surface growth factor and
      cytokine receptors. This ligand-independent receptor activation induces multiple
      downstream signaling pathways that regulate expression of multiple genes. These
      signaling pathways converge to stimulate transcription factor AP-1. Among genes
      whose expression is regulated by AP-1 are several matrix-metalloproteinase (MMP)
      family members and type I procollagen. UV-enhanced matrix degradation is
      accompanied with decreased collagen production mediated not only by activation of
      AP-1, but also by inhibition of transforming growth factor (TGF)-beta signaling.
      Several alterations to skin connective tissue that occur during aging are
      mediated by mechanisms that are similar to those that occur in response to UV
      irradiation. Thus, skin aging is associated with increased AP-1 activity,
      increased MMP expression, impaired TGF-beta signaling, enhanced collagen
      degradation, and decreased collagen synthesis. Knowledge gained from examining
      molecular responses of human skin to UV irradiation provides not only a framework
      for understanding mechanisms involved in skin aging, but also may help in
      development of new clinical strategies to impede chronological and UV-induced
      skin aging.

PMID- 12208240
TI  - Circadian and age-related modulation of thermoreception and temperature
      regulation: mechanisms and functional implications.
AB  - At older ages, the circadian rhythm of body temperature shows a decreased
      amplitude, an advanced phase, and decreased stability. The present review
      evaluates to what extent these changes may result from age-related deficiencies
      at several levels of the thermoregulatory system, including thermoreception,
      thermogenesis and conservation, heat loss, and central regulation. Whereas some
      changes are related to the aging process per se, others appear to be secondary to
      other factors, for which the risk increases with aging, notably a decreased level
      of fitness and physical activity. Moreover, functional implications of the body
      temperature rhythm are discussed. For example, the relation between circadian
      rhythm and thermoregulation has hardly been investigated, while evidence showed
      that sleep quality is dependent on both aspects. It is proposed that the
      circadian rhythm in temperature in homeotherms should not be regarded as a
      leftover of ectothermy in early evolution, but appears to be of functional
      significance for physiology from the level of molecules to cognition. A new view
      on the functional significance of the circadian rhythm in peripheral vasodilation
      and the consequent out-of-phase rhythms in skin and core temperature is
      presented. It is unlikely that the strong, daily occurring, peripheral
      vasodilation primarily represents heat loss in response to a lowering of set
      point, since behavioral measures are simultaneously taken in order to prevent
      heat loss. Several indications rather point towards a supportive role in
      immunological host defense mechanisms. Given the functional significance of the
      temperature rhythm, research should focus on the feasibility and effectiveness of
      methods that can in principle be applied in order to enhance the weakened
      circadian temperature rhythm in the elderly.

PMID- 12208241
TI  - Risk factors for intraoperative epithelial defect in laser in-situ
      keratomileusis.
AB  - PURPOSE: To report intraoperative epithelial defects (IED) in eyes undergoing
      laser in-situ keratomileusis (LASIK). DESIGN: Consecutive interventional case
      series. METHODS: Retrospective review of 247 eyes (133 patients) that underwent
      primary LASIK by a single surgeon at an academic institution using the Hansatome
      microkeratome. Patient characteristics and variations in preoperative and
      operative technique were analyzed. The main outcome measure was occurrence of IED
      (defined as loose epithelium that is > 1 mm or cannot be stably repositioned or
      absent epithelium). Multivariate logistic regression was performed. RESULTS:
      Intraoperative epithelial defects occurred in 24 (9.7%) of 247 eyes.
      Intraoperative epithelial defects significantly increased with older age (odds
      ratio [OR] 2.39/decade; 95% confidence interval [CI] 1.46-3.92), thicker
      preoperative corneal thickness (OR 2.30/50 microm; 95% CI 1.24-4.28), and
      maintenance of suction ring vacuum during the reverse pass of the microkeratome
      (OR 1.76; 95% CI 1.01-3.06). The preoperative and intraoperative eye-drop regimen
      (anesthetic, mydriatics, lubricants, and intraoperative tonometry) had a
      significant effect on IED risk (OR, 0.163 best vs worst regimen; 95% CI, 0.033
      0.792). In patients undergoing bilateral LASIK, the incidence of IED is much
      higher in the second eye if the first eye developed an IED (57% vs 1%).
      CONCLUSIONS: Modifying the eyedrop regimen was the more effective technical
      approach to decrease the risk of IED. Age and corneal thickness are valuable
      patient characteristics for preoperative risk assessment. Intraoperative
      epithelial defects in the first eye is highly predictive of IED in the second eye
      of the same patient.

PMID- 12208243
TI  - Acute zonal occult outer retinopathy: a long-term follow-up study.
AB  - PURPOSE: To report the long-term follow-up of patients with acute zonal occult
      outer retinopathy (AZOOR). DESIGN: Observational consecutive case series.
      METHODS: Prospective and retrospective review of medical records of patients with
      AZOOR. RESULTS: Fifty-one patients (37 women and 14 men) with a median age of 33
      years (mean, age 36 years; range, 13-63 years) were followed for a median of 96
      months (mean 100 months; range, 36-420 months). At presentation, AZOOR was
      present in one eye of 31 patients (61%) and both eyes in 20 patients (39%). All
      patients presented with an acute loss of one or more zones of visual field, and
      45 (88%) patients presented with photopsia. Corrected visual acuity was 20/40 or
      better in 68 (76%) of 90 affected eyes. Funduscopic examination was normal in 82
      eyes and revealed signs of AZOOR in 8 eyes. Electroretinographic amplitudes were
      depressed in all affected eyes. The median delay in diagnosis of AZOOR was 17
      months. During follow-up, AZOOR developed in 19 fellow eyes. At final follow-up
      AZOOR was present in one eye of 12 (24%) patients and both eyes of 39 (76%)
      patients. Sixteen patients had 23 recurrences of AZOOR. Visual field loss
      stabilized within 6 months in 37 patients (72%), progressed stepwise in 2
      patients (4%), and partly improved in 12 patients (24%). Fourteen patients (28%)
      had autoimmune diseases, including Hashimoto's thyroiditis in 6 patients and
      relapsing transverse myelopathy in 4 patients. At last follow-up all patients had
      residual visual field defects. Final visual acuity was 20/40 or better in 61
      (68%) affected eyes. Nine patients (18%) were legally blind. The fundi of 90
      affected eyes revealed no changes of AZOOR in 47 eyes (52%) and changes in the
      pigment epithelium and retina caused by AZOOR in 43 eyes (48%). CONCLUSIONS:
      Visual loss in AZOOR is characterized by one or more episodes of acute
      dysfunction, and in some cases, death of retinal receptor cells in one or more
      zones of one or both eyes. Central vision is often spared, but recovery of visual
      field occurs infrequently. The etiology of AZOOR is unknown. Electroretinography
      is essential for early diagnosis. The value of treatment is uncertain.

PMID- 12208242
TI  - The fellow eye in NAION: report from the ischemic optic neuropathy decompression
      trial follow-up study.
AB  - PURPOSE: To examine the prevalence and incidence of second eye nonarteritic
      anterior ischemic optic neuropathy (NAION) and associated patient characteristics
      in patients enrolled in the Ischemic Optic Neuropathy Decompression Trial (IONDT)
      Follow-up Study. DESIGN: Randomized clinical trial with observational cohort.
      METHODS: Patients randomized to optic nerve sheath decompression surgery or
      careful follow-up had a diagnosis of acute unilateral NAION, visual acuity
      between 20/64 and light perception, and were aged 50 years or older. Eligible
      patients who declined randomization or whose visual acuity was better than 20/64
      were not randomized but followed as part of an observational cohort. Follow-up
      examinations took place at 3, 6, 12, 18, and 24 months and annually thereafter.
      RESULTS: Four hundred eighteen patients were enrolled; 258 randomized and 160
      observed. Previous NAION or other optic neuropathy was present in the fellow eye
      of 21.1% (88/418) of patients at baseline. Four patients developed optic
      neuropathy in the fellow eye at follow up that could not be conclusively
      diagnosed as NAION. New NAION in the fellow eye occurred in 14.7% (48/326) of
      patients at risk during a median follow up of 5.1 years. Randomized patients
      experienced a higher incidence (35/201; 17.4%) than nonrandomized patients
      (13/125; 10.4%). A history of diabetes and baseline visual acuity of 20/200 or
      worse in the study eye, but not age, sex, aspirin use, or smoking were
      significantly associated with new NAION in the fellow eye. Final fellow eye
      visual acuity was significantly worse in those patients with new fellow eye NAION
      whose baseline study eye visual acuity was 20/200 or worse. CONCLUSIONS: Follow
      up data from the IONDT cohort provide evidence that the incidence of fellow eye
      NAION is lower than expected: new NAION was diagnosed in 14.7% of IONDT patients
      over approximately 5 years. Increased incidence is associated with poor baseline
      visual acuity in the study eye and diabetes, but not age, sex, smoking history,
      or aspirin use.

PMID- 12208244
TI  - Spontaneous closure of traumatic macular hole.
AB  - PURPOSE: To investigate the mechanism by which traumatic macular hole closes
      spontaneously. DESIGN: Consecutive observational case series of three patients
      with unilateral traumatic macular hole who consulted medical staff at the Kansai
      Medical University between 1997 and 2000. METHODS: Three patients who sustained
      unilateral blunt trauma to the eye and developed traumatic macular hole were
      followed with ophthalmic examination, fundus photography, fluorescein
      angiography, and optical coherence tomography (OCT). RESULTS: Case 1 was an 11
      year-old boy. He had neither a macular hole nor prominent macular edema at his
      first consultation, but a macular hole opened 3 weeks later. OCT showed macular
      edema and a full-thickness macular hole. The tissue around the edge of the
      macular hole protruded inward toward the center and finally closed spontaneously
      18 weeks later. Case 2 was a 19-year-old man. He had a tiny rough-edged macular
      hole at his first consultation with a local ophthalmologist. OCT showed macular
      hole enlargement and worsening of the macular edema during follow up. The macular
      hole finally closed 4 months after injury. Case 3 was a 15-year-old boy. He had a
      tiny rough-edged macular hole at his first consultation with a local
      ophthalmologist. The macular hole finally closed 6 months after injury.
      CONCLUSION: Macular hole can be a result of severe damage from ocular concussion
      or damage to the retina. For 6 months following injury, traumatic macular hole
      should probably be observed rather than surgically repaired, because of the
      possibility that the macular hole may close spontaneously.

PMID- 12208245
TI  - Unbalanced vitreous levels of pigment epithelium-derived factor and vascular
      endothelial growth factor in diabetic retinopathy.
AB  - PURPOSE: To determine the levels of pigment epithelium-derived factor (PEDF) and
      vascular endothelial growth factor (VEGF) in the vitreous of patients with
      diabetic retinopathy (DR). DESIGN: Experimental study of PEDF and VEGF levels in
      vitreous samples collected during vitrectomy. METHODS: The levels of PEDF and
      VEGF were measured by enzyme-linked immunosorbent assay in the vitreous of 46
      eyes of 43 patients who underwent vitrectomy with diabetic retinopathy (DR) (32
      eyes of 29 patients) and an idiopathic macular hole (MH) (14 eyes of 14
      patients). RESULTS: The vitreal concentration of PEDF was significantly lower at
      1.11 +/- 0.14 microg/ml (mean +/- standard error) in eyes with DR than in eyes
      with MH at 1.71 +/- 0.22 microg/ml (P =.021). The VEGF level was 1799 +/- 478
      pg/ml in eyes with DR and not detectable in MH. The PEDF level in proliferative
      DR (PDR) (0.94 +/- 0.12 microg/ml) was lower than that in nonproliferative DR
      (NPDR) (2.25 +/- 0.32 microg/ml), and that in active DR (0.85 +/- 0.14 microg/ml)
      was significantly lower than that in inactive DR (1.59 +/- 0.24 microg/ml; P
      =.01). The VEGF level was 2025 +/- 533 pg/ml in PDR and 215 +/- 201 pg/ml in NPDR
      and that in active DR (2543 +/- 673 pg/ml) was significantly higher than that in
      inactive DR (395 +/- 188 pg/ml; P =.0098). CONCLUSIONS: These results suggest
      that lower levels of PEDF and higher levels of VEGF may be related to the
      angiogenesis in DR that leads to active PDR.

PMID- 12208246
TI  - Correlation between retinal abnormalities and intracranial abnormalities in the
      shaken baby syndrome.
AB  - PURPOSE: To report correlation between retinal and intracranial abnormalities and
      to evaluate pathogenesis of retinal hemorrhages in the shaken baby syndrome
      (SBS). DESIGN: Observational case series. METHODS: Seventy-five children with
      apparent nonaccidental head trauma consistent with SBS had complete physical
      examination, complete ophthalmologic examination, neuroimaging by CT or MRI, or
      both, and skeletal radiographic survey. In this retrospective review,
      ophthalmoscopic and intracranial abnormalities were correlated. RESULTS: The age
      of patients ranged from 2 to 48 months (mean - SD, 10.6 +/- 10.4 months).
      Neuroimaging was abnormal in all 75 cases. Findings included subdural hematoma
      (70 children, 93%), cerebral edema (33 children, 44%), subarachnoid hemorrhage
      (12 children, 16%), vascular infarction (nine children, 12%), intraparenchymal
      blood (six children, 8%), parenchymal contusion (six children, 8%), and epidural
      hemorrhage (one child, 1%). Sixty-four (64/75, 85%) children had retinal
      abnormalities, mostly (53/64, 82%) confluent multiple hemorrhages that were
      subretinal, intraretinal, and preretinal in 47/64 (74%) and bilateral in 52/64
      (81%). No association was found between anatomic site (left, right, or bilateral)
      of intracranial and retinal findings (McNemar test kappa = -0.026-0.106) or
      between any of the intracranial findings mentioned above and the following
      retinal findings: normal or abnormal retinal examination, multiple (>10) or few
      retinal hemorrhages (< or =10), symmetric or asymmetric retinal findings, or
      retinoschisis (kappa = -0.127-0.104). Signs of possible increased intracranial
      pressure were not correlated with any retinal abnormality (kappa = -0.03-0.073).
      There was no correlation between evidence of impact trauma to the head and
      retinal hemorrhages (kappa = 0.058). Total Cranial Trauma Score and Total Retinal
      Hemorrhage Score, both indicating the severity of injury, were correlated (P
      =.032). CONCLUSIONS: Our study supports previous observations that the severity
      of retinal and intracranial injury is correlated in SBS. We cannot support the
      suggestions that in most children with SBS retinal bleeding is caused by
      sustained elevated intracranial, elevated intrathoracic pressure, direct tracking
      of blood from the intracranial space, or direct impact trauma. The correlation in
      severity of both eye and head findings may suggest, however, that retinal
      abnormalities are the result of mechanical shaking forces.

PMID- 12208247
TI  - Photodynamic therapy with verteporfin for choroidal neovascularization in
      patients with angioid streaks.
AB  - PURPOSE: To evaluate safety and efficacy of photodynamic therapy with verteporfin
      for subfoveal choroidal neovascularization associated with angioid streaks.
      DESIGN: Prospective interventional case series. METHODS: Eight patients (eight
      eyes) with subfoveal choroidal neovascularization secondary to angioid streaks
      were reviewed. Standardized protocol refraction, visual acuity testing,
      ophthalmologic examinations, color photographs, fluorescein angiograms and
      indocyanine angiograms were used to evaluate the results of photodynamic therapy
      with verteporfin. Follow up ranged from 6 to 12 months with a mean (+/- SD) of
      8.75 (+/- 2.37) months. RESULTS: Photodynamic therapy with verteporfin was well
      tolerated in patients with choroidal neovascularization related to angioid
      streaks. No deterioration in visual acuity was observed. Increase in median best
      corrected visual acuity was 1.37 lines (SD +/- 1.59 lines, range 1-5 lines) at
      the last follow up. Two (25%) patients had no improvement of visual acuity. At
      the last follow up three (37.5%) patients showed no leakage and three (37.5%)
      patients had minimal leakage from choroidal neovascularization. Photodynamic
      therapy related ocular complications were not reported in any case. CONCLUSIONS:
      Photodynamic therapy with verteporfin generally achieved short-term cessation of
      or decrease of fluorescein leakage from subfoveal choroidal neovascularization
      without loss of vision in patients with angioid streaks. Further studies with
      longer follow up are necessary to confirm whether verteporfin therapy is
      beneficial for subfoveal choroidal neovascularization related to angioid streaks.

PMID- 12208248
TI  - Basic fibroblast growth factor, glutamine synthetase, and interleukin-6 in
      vitreous fluid from eyes with retinal detachment complicated by proliferative
      vitreoretinopathy.
AB  - PURPOSE: To investigate the presence of basic fibroblast growth factor (bFGF),
      glutamine synthetase (GS), and interleukin-6 (IL-6) in vitreous fluid from eyes
      with retinal detachment complicated by proliferative vitreoretinopathy (PVR).
      DESIGN: Comparative case series; experimental study. METHODS: In a prospective
      study, we measured bFGF, GS, IL-6, and total protein in vitreous fluid samples
      from 53 eyes from 53 consecutive patients with PVR operated on in our hospital.
      As controls, vitreous fluid samples from eyes with a macular hole (n = 9) or
      pucker (n = 11) were used. MAIN OUTCOME MEASURES: Laboratory data of the patient
      group were compared with the control group and correlated with various clinical
      data, especially with visual recovery and redetachment. RESULTS: For IL-6, bFGF,
      and total protein we found significantly higher levels in PVR patients' eyes than
      in control eyes (P =.03, P =.046, and P <.0001, respectively). Within the PVR
      group, no significant correlation was found for IL-6, bFGF, GS, or total protein
      with the various tested clinical variables. CONCLUSIONS: We found increased
      levels of IL-6, bFGF, and total protein in vitreous fluid from patients' eyes
      with PVR. Whether the increased levels of IL-6, bFGF, and total protein are the
      result of an injury-induced upregulation of these proteins as part of a self
      protective mechanism of the retina to minimize photoreceptor damage after the
      mechanical injury induced by retinal detachment is, at present, not known.

PMID- 12208249
TI  - Free insulin growth factor-I and vascular endothelial growth factor in the
      vitreous fluid of patients with proliferative diabetic retinopathy.
AB  - PURPOSE: To investigate the relationship between insulin-like growth factor-I
      (IGF-I) and vascular endothelial growth factor (VEGF) in the vitreous fluid of
      diabetic patients with proliferative diabetic retinopathy (PDR). DESIGN:
      Observational case-control study. METHODS: In a prospective study, 37 consecutive
      diabetic patients with PDR (14 type I and 23 type II diabetes mellitus) in whom a
      vitrectomy was performed were compared with 21 nondiabetic patients with other
      conditions requiring vitrectomy (control group). Free IGF-I and VEGF were
      measured by ELISA. RESULTS: Vitreal levels of both free IGF-1 and VEGF were
      higher in diabetic patients with PDR than in control subjects (P <.01, and P
      <.0001, respectively). After adjusting for total intravitreous protein
      concentration, VEGF (ng/mg of proteins) remained significantly higher in diabetic
      patients with PDR than in the control group (P <.0001), whereas free IGF-I (ng/mg
      of proteins) was lower in diabetic patients than in control subjects (P <.0001).
      The vitreous concentrations of VEGF were higher in patients with active PDR than
      in patients with quiescent PDR (P <.005), whereas vitreous free IGF-I was not
      related to PDR activity. Finally, we did not observe a correlation between the
      vitreal levels of free IGF-I and VEGF. CONCLUSIONS: We conclude that free IGF-I
      and VEGF are both increased, but not related, within the vitreous fluid of
      diabetic patients with PDR. In addition, our results support the current concept
      that VEGF is directly involved in the pathogenesis of PDR, whereas the precise
      role of free IGF-I remains to be established.

PMID- 12208250
TI  - Cancer-associated retinopathy associated with invasive thymoma.
AB  - PURPOSE: To report a case of cancer-associated retinopathy associated with
      invasive thymoma. DESIGN: Interventional case report. METHOD: A 41-year-old
      Japanese woman was observed between February 1998 and May 2001. Ophthalmologic
      examinations and systemic examinations were performed. The patient received
      treatment including corticosteroid pulse therapy, plasmapheresis, and thymectomy.
      RESULTS: The patient developed progressive visual dysfunction including bilateral
      visual acuity loss, concentric contraction of visual fields, and color vision
      loss. In both eyes, retinal vessel attenuation and retinal pigment epithelium
      degeneration were observed with fundus ophthalmoscopy and fluorescein
      angiography. Response in electroretinogram was reduced, suggesting both rod and
      cone dysfunction. Autoantibody against 23-kD cancer-associated retinopathy (CAR)
      antigen (antirecoverin antibody) was detected in the patient's serum. A
      mediastinal tumor that was histopathologically diagnosed as invasive thymoma was
      detected and was surgically resected. During more than 3 years of follow-up, no
      other malignancy was detected despite extensive systemic evaluation. The patient
      also suffered from subclinical myasthenia gravis. Although temporary improvement
      of visual function was observed after treatment with steroid pulse therapy and
      plasmapheresis' light perception of each eye was lost in the end. CONCLUSIONS:
      The patient was diagnosed as having CAR. Invasive thymoma was considered to be
      the causative tumor because there had been no evidence that suggested other
      systemic malignancy during more than 3 years of follow-up.

PMID- 12208251
TI  - Risk factors for Type II diabetes and diabetic retinopathy in a mexican-american
      population: Proyecto VER.
AB  - PURPOSE: Risk factors for type II diabetes and diabetic retinopathy were
      determined in a population-based study of Mexican-Americans. DESIGN: Proyecto VER
      (Vision, Evaluation, and Research) is a cross-sectional study in a random sample
      of the self-described Hispanic populations in Tucson and Nogales, Arizona, age 40
      and older. METHODS: Of 6,659 eligible subjects, 4,774 (72%) participated in the
      home questionnaire and clinic visit. Diabetes was defined as self-report of a
      physician diagnosis or hemoglobin A(1c) value of > or = 7.0%. Only type II
      diabetes was included. Diabetic retinopathy was assessed on stereo fundus
      photographs of all persons with diabetes. Questions were asked about demographic,
      personal, socioeconomic, and diabetes related variables. RESULTS: 1023 (21.4%) of
      the sample had type II diabetes, and 68% were in the low-income group (annual
      income less than $20,000). Diabetes was associated with Native-American ancestry,
      higher acculturation, low income, less education, and increasing body mass index
      after age and gender adjustment. Persons with previously undiscovered diabetes
      were more likely to have no regular source of care, no insurance, and currently
      smoke compared with persons with known diabetes. Only low income was related to
      proliferative retinopathy, once adjusted for other factors (odds ratio [OR] =
      3.93, 95%, confidence limitations [CL] = 1.31-11.80). CONCLUSIONS: Several
      socioeconomic and other factors were associated with diabetes, but few were
      related to diabetic retinopathy. Persons in the low-income group appeared to be
      at greater risk of diabetes and the ocular complications of diabetes compared
      with those with more income. Further longitudinal studies in this population are
      needed to confirm the associations.

PMID- 12208252
TI  - Progression of visual field loss in untreated glaucoma patients and glaucoma
      suspects in St. Lucia, West Indies.
AB  - PURPOSE: A 1986-1987 survey found 8.8% prevalence of open-angle glaucoma in the
      black population of St. Lucia, West Indies. This follow-up study assessed visual
      field loss progression in untreated glaucoma patients and glaucoma suspects 10
      years later. DESIGN: Cohort study. METHODS: Subjects were 205 glaucoma patients
      and suspects; 1987 data included age, sex, visual acuity, and visual fields
      measured by automated threshold perimetry (Humphrey C 30-2 test), and 1997 data
      included intraocular pressure, visual acuity, and visual fields measured by the
      same test. Exclusion criteria included field unreliability, field improvement due
      to vision improvement, nonglaucomatous vision deterioration, glaucoma treatment
      since 1988, and scoring of a visual field as end stage in 1987. Visual fields
      were scored by algorithms for the Advanced Glaucoma Intervention Study (AGIS) and
      Collaborative Initial Glaucoma Treatment Study (CIGTS). RESULTS: By AGIS
      criteria, 55% of 146 right eyes and 52% of 141 left eyes showed progression of
      visual field loss. In linear regressions, progression severity was unassociated
      with sex, intraocular pressure, or baseline visual field score, but was
      positively associated with age (P <.001, right; P =.002, left). The cumulative
      probability of reaching end stage in 10 years in at least one eye was
      approximately 16% by AGIS criteria. By CIGTS criteria, 73% of 146 right eyes and
      72% of 141 left eyes progressed. CONCLUSIONS: These data provide a unique
      opportunity to study progression of untreated glaucoma. The percentage of eyes
      showing visual field loss progression and the percentage reaching end stage were
      considerably higher than in studies of visual field progression in treated eyes.

PMID- 12208253
TI  - Vision-threatening complications of nasal T/NK lymphoma.
AB  - PURPOSE: Nasal T/NK lineage lymphoma, previously known as lethal midline
      granuloma, is common among Oriental, Native-American, and Hispanic patients and
      is invariably associated with Epstein-Barr virus. Nasal localization, local
      necrosis, angioinvasion, and aggressive behavior are hallmarks of the disease.
      Ophthalmologic symptoms and signs may precede lymphoma diagnosis or complicate
      its disease course. We aim to define the incidence and disease pattern of
      ophthalmic involvement. DESIGN: Retrospective single-institution consecutive
      interventional case series. METHODS: Records of all lymphoma patients from 1996
      to 2000 were retrieved from a computer database, and the primary sites and
      lineage were reviewed. Nasal T/NK lymphoma was defined by a combination of
      morphology, positive CD3 epsilon and CD56 expression, in situ hybridization
      staining for Epstein-Barr virus expressed RNA (EBER), and negative staining for B
      cell markers (CD20 and CD79a). RESULTS: Thirty-five consecutive patients with
      T/NK lymphoma were identified. Primary nasal or nasopharyngeal disease was found
      in 24 patients. Six (25%) of the 24 patients suffered from vision-threatening
      complications of two distinct categories, namely uveitis/vitritis and orbital
      infiltration. The former preceded the diagnosis of lymphoma in two patients and
      also led to novel ocular complications like rhegmatogenous retinal detachment and
      macular hole that were successfully managed by ocular surgery. In four patients,
      orbital extension of lymphomatous disease accompanied biopsy-proven in-field
      disease relapse. Generally, the prognosis is grave, but remission can still be
      achieved with aggressive combined chemotherapy and radiotherapy. CONCLUSION: Both
      oncologists and ophthalmologists should be aware of ocular complications when
      dealing with known or suspected cases of T/NK lymphoma at diagnosis and relapse.
      Regular ophthalmic assessment of these patients is warranted.

PMID- 12208254
TI  - A role for local inflammation in the formation of drusen in the aging eye.
AB  - PURPOSE: The accumulation of numerous or confluent drusen, especially in the
      macula, is a significant risk factor for the development of age-related macular
      degeneration (AMD). Identifying the origin and molecular composition of these
      deposits, therefore, has been an important, yet elusive, objective for many
      decades. Recently, a more complete profile of the molecular composition of drusen
      has emerged. DESIGN: In this focused review, we discuss these new findings and
      their implications for the pathogenic events that give rise to drusen and AMD.
      METHODS: Tissue specimens from one or both eyes of more than 400 human donors
      were examined by light, confocal or electron microscopy, in conjunction with
      antibodies to specific drusen-associated proteins, to help characterize the
      transitional events in drusen biogenesis. Quantification of messenger RNA from
      the retinal pigment epithelium (RPE)/choroid of donor eyes was used to determine
      if local ocular sources for drusen-associated molecules exist. RESULTS: The
      results indicate that cellular remnants and debris derived from degenerate RPE
      cells become sequestered between the RPE basal lamina and Bruch's membrane. We
      propose that this cellular debris constitutes a chronic inflammatory stimulus,
      and a potential "nucleation" site for drusen formation. The entrapped cellular
      debris then becomes the target of encapsulation by a variety of inflammatory
      mediators, some of which are contributed by the RPE and, perhaps, other local
      cell types; and some of which are extravasated from the choroidal circulation.
      CONCLUSIONS: The results support a role for local inflammation in drusen
      biogenesis, and suggest that it is analogous to the process that occurs in other
      age-related diseases, such as Alzheimer's disease and atherosclerosis, where
      accumulation of extracellular plaques and deposits elicits a local chronic
      inflammatory response that exacerbates the effects of primary pathogenic stimuli.

PMID- 12208255
TI  - Treatment of conjunctival squamous cell carcinoma with topical cidofovir.
AB  - PURPOSE: To describe a case of conjunctival squamous cell carcinoma in situ that
      was successfully treated with adjunctive topical cidofovir. DESIGN:
      Interventional case report. METHODS: A 52-year-old woman presented with a
      diagnosis of diffuse conjunctival papillomatosis in the right eye. She underwent
      conjunctival biopsy followed by a 6-week course of cidofovir eyedrops (2.5
      mg/ml). RESULTS: The biopsy specimen demonstrated squamous cell carcinoma in
      situ. After this biopsy and treatment with cidofovir, the mass regressed into a
      small vascular tuft, which was excised and treated with cryotherapy. Six months
      after cidofovir treatment, the patient developed cicatricial changes of the
      inferior punctum. No recurrence of the squamous cell carcinoma has occurred in 24
      months of follow-up. CONCLUSION: Cidofovir has shown effectiveness in the
      treatment of neoplastic lesions involving various mucus membrane sites. This
      antiviral drug may be a valuable addition to our treatment armamentarium for
      patients with squamous cell carcinoma in situ of the conjunctiva. The possible
      relationship between topical cidofovir and cicatricial changes of the lacrimal
      system cannot be determined from this isolated report, but further investigation
      is indicated.

PMID- 12208256
TI  - Bacillary angiomatosis of the anterior orbit, eyelid, and conjunctiva.
AB  - PURPOSE: To report a case of bacillary angiomatosis of the lower eyelid,
      conjunctiva, and anterior orbit. DESIGN: Interventional case report. METHODS: A
      76-year-old immunocompromised male patient developed a firm vascularized nodule
      in his left lower eyelid and anterior orbit. RESULTS: An excisional biopsy was
      performed. Histopathologic examination revealed an abnormal vascular
      proliferation and a mixed inflammatory infiltrate. A Warthin-Starry stain showed
      numerous bacilli. These findings are characteristic of bacillary angiomatosis. A
      serologic specimen was positive for antibodies to Bartonella Quintana.
      CONCLUSION: The lower lid and anterior orbit are rare locations for bacillary
      angiomatosis. Our case brings to attention the increasing importance of
      Bartonella infection as a causative agent of ophthalmic diseases.

PMID- 12208257
TI  - Colletotrichum keratitis.
AB  - PURPOSE: To evaluate Colletotrichum keratitis and to report the risk factors and
      clinical course. DESIGN: Interventional case series. METHODS: In order to report
      the clinical course of Colletotichum keratitis, fungal keratitis cases between
      January 1980 and February 2001 in an institutional setting were retrospectively
      reviewed and 10 eyes of 9 patients with Colletotrichum keratitis were identified
      by positive cultures. RESULTS: Colletotrichum species were identified in 10 of
      360 culture-proven fungal keratitis cases. All cases were sensitive to
      amphotericin B, three of the isolates showed resistance to natamycin, two
      isolates had intermediate sensitivity to natamycin, and one isolate was resistant
      to fluconazole. Natamycin 5% was used as the initial antifungal agent in eight
      microbiologically proven fungal keratitis cases. Two of nine patients continued
      the treatment with amphotericin B 0.15% after the sensitivity results were
      obtained. CONCLUSION: Colletotrichum is an infrequent cause of fungal keratitis.
      The risk factors are similar to the known fungal keratitis. Colletotrichum is
      resistant to natamycin in vitro; however, all our patients responded well to this
      treatment while resistance or intermediate sensitivity to natamycin and
      resistance to fluconazole was observed.

PMID- 12208258
TI  - Caruncle tumor as the first sign of metastatic lung carcinoma.
AB  - PURPOSE: Report of a neuroendocrine carcinoma of the caruncle as the first sign
      of a metastatic lung carcinoma. DESIGN: Interventional case report. METHODS:
      Excision of a rapidly growing caruncular tumor in a 76-year-old woman with a
      history of breast cancer. RESULTS: Pathology revealed a large cell neuroendocrine
      carcinoma, consistent with metastatic lung carcinoma. Computerized tomography of
      chest, abdomen, and a bone scan disclosed signs of malignancy in the lungs,
      liver, and bones, originally considered as metastatic breast cancer. However,
      this diagnosis was excluded on the basis of histopathological findings and
      clonality analysis. A primary neuroendocrine (Merkel cell) carcinoma was ruled
      out on morphologic and immunohistochemical grounds. CONCLUSION: We present a
      unique case of a metastatic large cell neuroendocrine carcinoma of the caruncle.

PMID- 12208259
TI  - Unilateral acquired upper eyelid ptosis and decreasing nystagmus.
AB  - PURPOSE: To describe a patient with congenital nystagmus that decreased in one
      eye after the development of a cavernous sinus meningioma. DESIGN: Interventional
      case report. METHODS: A 45-year-old man with congenital nystagmus, albinism, and
      high myopia presented with right upper eyelid ptosis that was corrected
      surgically on three occasions during a 3-year period. An episode of syncope was
      followed by diagnostic evaluation that disclosed a cavernous sinus meningioma. He
      commented that his right eye nystagmus progressively decreased. He was found to
      have ophthalmoplegia on the right eye due to nerve compression by the meningioma.
      RESULTS: A magnetic resonance imaging scan disclosed a cavernous sinus meningioma
      extending into the parachiasmal and clival areas. A biopsy specimen of the lesion
      demonstrated a meningioma. CONCLUSIONS: Any patient with acquired ptosis should
      have a complete ophthalmic examination, including evaluation of extraocular
      motility.

PMID- 12208260
TI  - Repair of cicatricial ectropion in an infant with harlequin ichthyosis using
      engineered human skin.
AB  - PURPOSE: To report the use of an Apligraf (Organogenesis, Inc., Canton,
      Massachusetts, USA) human skin equivalent for repair of cicatricial ectropion in
      a patient with harlequin ichthyosis. DESIGN: Interventional case report. METHODS:
      A 6-week-old male child with harlequin ichthyosis and severe bilateral upper
      eyelid cicatricial ectropion underwent repair with Apligraf grafts. RESULTS:
      After the initial repair with Apligraf grafts, recurrent bilateral upper eyelid
      ectropion developed, requiring repeat Apligraf grafting at age 61 days. After the
      second graft, the eyelids remained well positioned until the child's sudden death
      from respiratory failure at age 6 months. CONCLUSION: Apligraf human skin
      equivalent facilitated the repair of cicatricial ectropion in a child with
      harlequin ichthyosis.

PMID- 12208262
TI  - Choroidal metastasis in disseminated lung cancer: frequency and risk factors.
AB  - PURPOSE: To determine frequency, risk factors, and benefit of a prospective
      screening for intraocular metastasis in patients with metastatic lung cancer.
      DESIGN: Consecutive observational case series. METHODS: An ophthalmologic
      screening was performed on 84 consecutive patients suffering from metastatic lung
      cancer. Medical history and disease stage were evaluated in regard to the risk
      for intraocular metastasis. RESULTS: In six patients (7.1%) choroidal metastasis
      (CM) was detected. Choroidal metastasis was present only when at least two other
      organ system were affected by metastasis (P =.03). The choroid was the sixth
      common site of organ metastasis. Mean remaining life span in patients with CM was
      1.9 (0.2-5.9) months. CONCLUSIONS: Choroidal metastasis is common in advanced
      metastatic lung cancer. However, due to the short survival of affected
      individuals, a systematic screening of at-risk patients for CM seems to be of
      limited benefit.

PMID- 12208261
TI  - Bilateral panuveitis in a child with hypohidrotic ectodermal dysplasia.
AB  - PURPOSE: To report a case of bilateral panuveitis in a patient with hypohidrotic
      ectodermal dysplasia. DESIGN: Interventional case report. METHODS: A 6-year-old
      African-American boy with hypohidrotic ectodermal dysplasia presented with pain,
      photophobia, and decreased vision in both eyes. RESULTS: Findings included severe
      bilateral panuveitis with optic disk edema, macular epiretinal membrane,
      peripheral retinal vasculitis, and retinitis. All other known causes of
      panuveitis were explored and ruled out. CONCLUSIONS: The abnormal development of
      tissues of ectodermal origin evident in hypohidrotic ectodermal dysplasia may
      include a predisposition to panuveitis.

PMID- 12208263
TI  - Spontaneous resolution of bilateral stage 1 macular holes documented by optical
      coherence tomography.
AB  - PURPOSE: To describe a case of spontaneous resolution of bilateral stage 1
      macular holes documented using optical coherence tomography. DESIGN:
      Observational case report. METHODS: A patient presented with blurring and
      distortion in the right eye. Optical coherence tomography showed a stage 1
      macular hole manifested as a foveal pseudocyst. The left eye appeared normal.
      RESULTS: On 6-month follow-up, symptoms had resolved in the right eye but had
      developed in the left eye. Optical coherence tomography revealed normal anatomy
      in the right eye with a foveal pseudocyst in the left eye. At 10 months, the
      patient was asymptomatic and had normal foveal anatomy in both eyes on optical
      coherence tomography. CONCLUSION: Stage 1 macular holes may appear as foveal
      pseudocysts on optical coherence tomography. In such cases, optical coherence
      tomography can provide definitive diagnostic information when clinical
      examination is equivocal. The observation and spontaneous resolution of bilateral
      stage 1 holes documented by optical coherence tomography are unique and
      interesting events of which a MEDLINE search found no previous reports.

PMID- 12208264
TI  - Successful treatment of orthodontic-associated traumatic endophthalmitis.
AB  - PURPOSE: To report successful management of orthodontic-associated traumatic
      endophthalmitis. DESIGN: Interventional case report. METHODS: A 17-year-old boy
      developed endophthalmitis after a penetrating corneal injury produced during
      removal of an orthodontic wire. Treatment included pars plana vitrectomy (PPV)
      with broad-spectrum intravitreal and systemic antibiotics. RESULTS: Clinical
      endophthalmitis resolved after PPV with injection of intravitreal vancomycin (1
      mg) and ceftazidime (2.25 mg), along with oral ciprofloxacin (750 mg twice
      daily). Microbiologic cultures of intraocular samples produced Staphylococcus
      epidermidis, Streptococcus viridans, and Lactobacillus species. Visual acuity
      improved to 20/20. CONCLUSIONS: Orthodontic-associated endophthalmitis can
      involve multiple organisms. It can be successfully treated with current treatment
      modalities, including PPV, intravitreal antibiotics, and systemic antibiotics.

PMID- 12208265
TI  - Mesectodermal leiomyoma exclusively involving the posterior choroid.
AB  - PURPOSE: To report a mesectodermal leiomyoma of the posterior choroid. DESIGN:
      Observational case report. METHODS: A 23-year-old man was referred to us because
      of a progressive blurred vision in his left eye. Ophthalmologic examination
      revealed the presence of a 12 x 10 x 7.2-mm amelanotic choroidal mass in his left
      posterior pole. Fluorescein angiography, A-scan ultrasonography, and B-scan
      echography findings were suggestive for a diagnosis of choroidal amelanotic
      melanoma. These clinical features prompted us to enucleate the left eye. RESULTS:
      Histopathological and immunohistochemistry examinations established a definitive
      diagnosis of mesectodermal leiomyoma of the posterior choroid. CONCLUSION: This
      case represents the first report describing the occurrence of an intraocular
      mesectodermal leiomyoma that may exclusively involve the posterior choroid.

PMID- 12208266
TI  - Evaluation of pulse corticosteroid therapy for vogt-koyanagi-harada disease
      assessed by optical coherence tomography.
AB  - PURPOSE: To evaluate the rapid effects of pulse corticosteroid therapy on the
      serous retinal detachment found at the acute phase of Vogt-Koyanagi-Harada
      disease. DESIGN: Interventional case series. METHODS: Nine Japanese patients
      determined to be at the acute phase of Vogt-Koyanagi-Harada disease with serous
      retinal detachment were treated with pulse corticosteroid therapy. Optical
      coherence tomography was used to follow the resolution of the retinal detachment.
      RESULTS: Optical coherence tomography images showed a marked decrease in the
      retinal detachment immediately after the first intravenous injection of
      corticosteroid and subsequent resolution. CONCLUSION: The rapid improvement of
      serous retinal detachment associated with Vogt-Koyanagi-Harada disease following
      pulse corticosteroid therapy supports an early therapeutic mechanism related to
      improved permeability of capillaries and permeability of the blood-retinal
      barrier rather than an anti-inflammatory or immunosuppressive action.

PMID- 12208267
TI  - Ocular and central nervous system paracoccidioidomycosis in a pregnant woman with
      acquired immunodeficiency syndrome.
AB  - PURPOSE: To describe an atypical case of central nervous system and ocular
      paracoccidioidomycoses simulating ocular toxoplasmosis in a pregnant woman with
      acquired immunodeficiency syndrome (AIDS). DESIGN: Interventional case report.
      METHODS: Case report. RESULTS: A 25-year-old pregnant woman with AIDS, presented
      with a severe ocular inflammation in the right eye involving the choroid, retina,
      and the optic disk, which rapidly progressed to retinal detachment, iris
      neovascularization, and neovascular glaucoma. The left eye was normal. Magnetic
      resonance imaging (MRI) showed a focal hypodense contrast-enhanced ring lesion in
      the brain. Serum antibody titers were negative for Toxoplasma gondii, but the
      polymerase chain reaction was positive for the parasite in the vitreous sample.
      The patient responded partially to specific treatment for toxoplasmosis, and
      there was a small reduction in size of the brain lesion. She progressed to a
      blind painful eye, which was enucleated. Paracoccidioides brasiliensis was found
      in the histopathological studies of the eye and oropharynx. With the diagnosis of
      disseminated ocular paracoccidioidomycoses, the patient was treated with
      trimethoprim-sulfamethoxazole with a satisfactory outcome and reduction in size
      of the brain lesion. CONCLUSION: Although ocular infection with ocular
      paracoccidioidomycoses is rare, this diagnosis should be considered when
      investigating ocular inflammation in a patient with AIDS.

PMID- 12208268
TI  - Elevation of one eye during tooth brushing.
AB  - PURPOSE: To describe a patient with congenital fibrosis of the extraocular
      muscles (CFEOM) and elevation of one eye during tooth brushing. METHODS: A 9
      month-old girl underwent full ophthalmologic examination. Exonic and flanking
      intronic sequences of the CFEOM2 ARIX gene were sequenced. RESULTS: The patient's
      clinical findings were consistent with classic CFEOM including chin elevation,
      bilateral ptosis, infraducted globes, no voluntary ocular elevation beyond
      midline, and convergence on attempted upgaze. During tooth brushing her right eye
      elevated beyond midline. This was elicited only by touching her teeth or gums but
      not by mouth movements. No ARIX mutations were detected. CONCLUSION: This is the
      first case described with CFEOM and aberrant regeneration between the nerve to
      the superior rectus and the trigeminal nerve. This aberrant innervation supports
      a primary developmental abnormality of the cranial nerves in CFEOM.

PMID- 12208269
TI  - Eye-rubbing optic neuropathy.
AB  - PURPOSE: To describe a patient whose "normal tension glaucoma" appears to have
      been produced by a long-standing habit of repetitive, bilateral eye rubbing.
      DESIGN: Observational case report. METHODS: A 46-year-old man presented with a
      "haze" over the left eye and had progressive bilateral optic neuropathy
      associated with bilateral normal intraocular pressure, pathological cupping of
      the optic disks, and nerve fiber bundle visual field defects. RESULTS: Over a 4
      year period, vision in the left eye deteriorated to no light perception.
      Progressive deterioration in the right eye stopped only after the patient ceased
      a 20-year habit of forceful rubbing of his eyes. After that, the decline in
      vision was terminated and both visual acuity and visual field were stabilized
      over an 8-year follow-up. CONCLUSION: It may be appropriate to include "eye
      rubbing" in the differential diagnosis of unexplained progressive optic
      neuropathy in presumed normal tension glaucoma.

PMID- 12208270
TI  - Incomplete congenital stationary night blindness associated with symmetrical
      retinal atrophy.
AB  - PURPOSE: To describe a Japanese patient with incomplete congenital stationary
      night blindness (iCSNB) with atypical retinal atrophy and kinetic visual field
      defects. METHODS: An ophthalmologic examination was performed, and the CACNA1F
      gene was analyzed by direct genomic sequencing. RESULTS: The patient had a
      hemizygous Arg913stop mutation in CACNA1F and had electroretinographic changes
      that were typical of iCSNB. The fundus had atrophic retinal lesions around the
      inferior vascular arcades OU, and Goldmann kinetic perimetry showed relative
      scotomas in the corresponding areas. CONCLUSIONS: Although most patients with
      iCSNB show essentially normal fundi without visual field defects, this case
      demonstrated retinal atrophy associated with visual field defects indicating a
      phenotypic heterogeneity induced by the CACNA1F mutation.

PMID- 12208271
TI  - Novel de novo mutation in CRX gene in a Japanese patient with leber congenital
      amaurosis.
AB  - PURPOSE: To report a novel de novo mutation in the cone-rod homeobox (CRX) gene
      in a Japanese patient with Leber congenital amaurosis (LCA). METHODS: The CRX
      gene was analyzed by direct genomic sequencing in a patient with LCA and in his
      healthy parents. A complete ophthalmologic examination was performed on the
      family. RESULTS: A heterozygotic deletion of G at nucleotid 520 in CRX,
      predicting a frameshift in codon 174 and a premature termination of translation
      [Ala174(1-bp del)], was identified in the proband. The mutation was not present
      in his unaffected parents. CONCLUSION: A novel de novo mutation in CRX was found
      in a Japanese patient with LCA.

PMID- 12208272
TI  - Transplantation of autologous retinal pigment epithelium in eyes with foveal
      neovascularization.

PMID- 12208274
TI  - Transplantation of autologous retinal pigment epithelium in eyes with foveal
      neovascularization.

PMID- 12208276
TI  - Diffusion-weighted MRI in shaken baby syndrome.

PMID- 12208278
TI  - A frame shift mutation in a tissue-specific alternatively spliced exon of
      collagen 2A1 in Wagner's vitreoretinal degeneration.

PMID- 12208280
TI  - Inferior oblique muscle location after enucleation and eviseration.

PMID- 12208295
TI  - Running energetics of the North American river otter: do short legs necessarily
      reduce efficiency on land?
AB  - Semi-aquatic mammals move between two very different media (air and water), and
      are subject to a greater range of physical forces (gravity, buoyancy, drag) than
      obligate swimmers or runners. This versatility is associated with morphological
      compromises that often lead to elevated locomotor energetic costs when compared
      to fully aquatic or terrestrial species. To understand the basis of these
      differences in energy expenditure, this study examined the interrelationships
      between limb morphology, cost of transport and biomechanics of running in a semi
      aquatic mammal, the North American river otter. Oxygen consumption, preferred
      locomotor speeds, and stride characteristics were measured for river otters (body
      mass=11.1 kg, appendicular/axial length=29%) trained to run on a treadmill. To
      assess the effects of limb length on performance parameters, kinematic
      measurements were also made for a terrestrial specialist of comparable stature,
      the Welsh corgi dog (body mass=12.0 kg, appendicular/axial length=37%). The
      results were compared to predicted values for long legged terrestrial
      specialists. As found for other semi-aquatic mammals, the net cost of transport
      of running river otters (6.63 J kg(-1)min(-1) at 1.43 ms(-1)) was greater than
      predicted for primarily terrestrial mammals. The otters also showed a marked
      reduction in gait transition speed and in the range of preferred running speeds
      in comparison to short dogs and semi-aquatic mammals. As evident from the corgi
      dogs, short legs did not necessarily compromise running performance. Rather, the
      ability to incorporate a period of suspension during high speed running was an
      important compensatory mechanism for short limbs in the dogs. Such an aerial
      period was not observed in river otters with the result that energetic costs
      during running were higher and gait transition speeds slower for this versatile
      mammal compared to locomotor specialists.

PMID- 12208296
TI  - Developmental plasticity in aerobic performance in deer mice (Peromyscus
      maniculatus).
AB  - While several studies have examined the abiotic effects of altitude (low ambient
      temperatures and hypoxia) on the aerobic performance of small mammals, few have
      explored the effects of development and maturation at different altitudes on
      aerobic performance as adults. We examined the basal metabolism and aerobic
      performance of deer mice (Peromyscus maniculatus) under four different
      developmental and testing regimes: (1) reared (gestation through weaning) and
      tested at high altitude; (2) reared and tested at low altitude; (3) reared at low
      altitude and tested at high altitude after acclimation; and (4) reared at low
      altitude and tested in hypoxia without acclimation. We found that mice that
      developed and were tested at low altitudes had a higher aerobic capacity (both
      aerobic performance and basal metabolic rate) than those that developed, or were
      acclimated as adults, at high altitudes. In addition, we found that mice that
      developed at high altitude did not have a higher aerobic capacity than those that
      developed at low altitude and were acclimated to high altitude as adults. Both
      groups tested at high altitudes had higher hematocrits (% red blood cells) and
      hemoglobin than mice tested at low altitudes. Surprisingly, mice acclimated to
      low altitudes and given an instantaneous exposure to hypoxia did not suffer a
      depression in aerobic performance.

PMID- 12208297
TI  - The energetics of barnacle geese (Branta leucopsis) flying in captive and wild
      conditions.
AB  - Experimental data on the relationship between mean heart rate (f(H)) and mean
      rate of oxygen consumption (VO(2)) of captive barnacle geese during flights in a
      wind tunnel are assessed in terms of their capacity to predict the typical VO(2)
      of wild barnacle geese, based on the recordings of their f(H), while undertaking
      autumn migratory flights between Spitsbergen (78 degrees N) and Caerlaverock,
      Scotland (55 degrees N). A significant linear relationship has been demonstrated
      between the f(H) and simultaneously recorded VO(2) of a single barnacle goose (B
      B) flying in the wind tunnel (VO(2)=1.42 f(H)-304, r(2)=0.82, P<0.001, N=12
      flights). Data recorded from three additional geese (N=4 flights), lay within the
      95% prediction intervals of the relationship for goose B-B. When these geese
      (mean body mass=2.06 kg, n=4) were flown in the wind tunnel (WT) without the
      mask, they had a mean f(H) of 451+/-23 beats min(-1), yielding an estimate for
      VO(2) of 336+/-33 ml min(-1). However, f(H) has also been recorded from wild
      barnacle geese (mean migratory f(H) of 253 beats min(-1)), and substitution of
      this value into the above calibration equation results in an unrealistically low
      value for mean migratory VO(2) of only 55 ml min(-1). Various factors, such as
      differences in heart mass, selective tissue perfusion, environmental temperature
      and flock formation, which might account for some of the difference in f(H)
      between the captive and wild geese are discussed. Comparison with other WT
      studies shows that inter-species minimum mass-specific VO(2) declines with
      increasing body mass (M(b); range 0.035-2.8 kg) as 173 M(b)(-0.224), r(2)=0.848.

PMID- 12208298
TI  - The respiratory system in varanid lizards: determinants of O(2) transfer.
AB  - Varanids in general exhibit greater aerobic capacities than other lizards. In a
      similar approach to the extensive investigations undertaken in mammals, the
      respiratory system in varanids is examined in terms of oxygen transfer from the
      air to the blood during rest and sustained locomotory activity. The parameters
      controlling the transfer of O(2) through the various steps of the respiratory
      system are appropriate to meet the maximum demands for oxygen with one possible
      exception, circulatory convection. Ventilatory convection is maintained during
      maximal aerobic locomotion ensuring adequate pulmonary ventilation and the
      protection of alveolar P(O(2)). Little evidence exists to indicate a mechanically
      imposed constraint to breathe and the possibility of a gular pump acting to
      assist ventilation, as a general feature of varanids remains to be determined.
      Alterations in the relative contributions of the ventilation-perfusion ratio,
      pulmonary diffusion, diffusion equilibrium and right-left shunts preserved the
      alveolar-arterial P(O(2)) difference, ensuring that arterial oxygenation was
      maintained. In those species where increases in cardiac output were limited,
      maximum O(2) transfer was achieved through increased extraction of oxygen at the
      tissues. Overall, the interrelationship of adjacent steps in the respiratory
      system ensures that one step cannot become limiting. Compensatory changes occur
      in various parameters to offset those parameters that are 'limited'. The high
      aerobic activity of varanid lizards would not be achievable without a compensated
      circulatory convection.

PMID- 12208299
TI  - Metabolic implications of a 'run now, pay later' strategy in lizards: an analysis
      of post-exercise oxygen consumption.
AB  - Lizards and many other animals often engage in locomotor behaviors that are of
      such short duration that physiological steady-state conditions are not attained.
      It is sometimes difficult to estimate the energetic costs of this type of
      locomotor activity. This difficulty is addressed by considering as reflective of
      the metabolic cost of activity (C(act)) not only the oxygen consumed during the
      activity itself, but also the excess post-exercise oxygen consumption (EPOC) and
      any excess metabolites persisting at the end of EPOC. Data from both lizards and
      mammals demonstrate that EPOC is the major energetic cost when activity is short
      and intense. This paper evaluates the major metabolic components of EPOC in
      lizards. We then examine how behavioral variables associated with locomotion
      (duration, intensity, frequency) can influence EPOC and C(act). Short and intense
      activity is much more expensive by this measure than is steady-state locomotion.
      Evidence is provided that intermittent activity of short duration can be more
      economical relative to single bouts of the same activity. Metabolic savings
      appear greatest when the pause period between behaviors is short. In contrast,
      endurance is enhanced by short activity periods and longer pause periods,
      suggesting a tradeoff between endurance and EPOC-related metabolic costs.

PMID- 12208300
TI  - Interactions between locomotion and ventilation in tetrapods.
AB  - Interactions between locomotion and ventilation have now been studied in several
      species of reptiles, birds and mammals, from a variety of perspectives. Among
      these perspectives are neural interactions of separate but linked central
      controllers; mechanical impacts of locomotion upon ventilatory pressures and
      flows; and the extent to which the latter may affect gas exchange and the
      energetics of exercise. A synchrony, i.e. 1:1 pattern of coordination, is
      observed in many running mammals once they achieve galloping speeds, as well as
      in flying bats, some flying birds and hopping marsupials. Other, non-1:1,
      patterns of coordination are seen in trotting and walking quadrupeds, as well as
      running bipedal humans and running and flying birds. There is evidence for an
      energetic advantage to coordination of locomotor and respiratory cycles for
      flying birds and running mammals. There is evidence for a mechanical constraint
      upon ventilation by locomotion for some reptiles (e.g. iguana), but not for
      others (e.g. varanids and crocodilians). In diving birds the impact of wing
      flapping or foot paddling on differential air sac pressures enhances gas exchange
      during the breath hold by improving diffusive and convective movement of air sac
      oxygen to parabronchi. This paper will review the current state of our knowledge
      of such influences of locomotion upon respiratory system function.

PMID- 12208301
TI  - Beyond U(crit): matching swimming performance tests to the physiological ecology
      of the animal, including a new fish 'drag strip'.
AB  - Locomotor performance of animals is of considerable interest from management,
      physiological, ecological and evolutionary perspectives. Yet, despite the
      extensive commercial exploitation of fishes and interest in the health of various
      fish stocks, the relationships between performance capacity, natural selection,
      ecology and physiology are poorly known for fishes. One reason may be the
      technical challenges faced when trying to measure various locomotor capacities in
      aquatic species, but we will argue that the slow pace of developing new species
      appropriate swim tests is also hindering progress. A technique developed for
      anadromous salmonids (the U(crit) procedure) has dominated the fish exercise
      physiology field and, while accounting for major advances in the field, has often
      been used arbitrarily. Here we propose criteria swimming tests should adhere to
      and report on several attempts to match swimming tests to the physiological
      ecology of the animal. Sprint performance measured with a laser diode/photocell
      timed 'drag strip' is a new method employing new technology and is reported on in
      some detail. A second new test involves accelerating water past the fish at a
      constant rate in a traditional swim tunnel/respirometer. These two performance
      tests were designed to better understand the biology of a bentho-pelagic marine
      fish, the Atlantic cod (Gadus morhua). Finally, we report on a modified
      incremental velocity test that was developed to better understand the biology of
      the blacknose dace (Rhinichthys atratulus), a Nearctic, lotic cyprinid.

PMID- 12208302
TI  - Environmental and functional limits to muscular exercise and body size in marine
      invertebrate athletes.
AB  - Many similarities exist between the key characteristics of muscular metabolism in
      marine invertebrates and those found in vertebrate striated muscle, even though
      there are important phosphagens and glycolytic end products that differ between
      groups. Lifestyles and modes of locomotion also vary extremely among
      invertebrates thereby shaping the pattern of exercise metabolism. In accordance
      with the limited availability of integrated ecological and physiological
      information the present paper reports recent progress in the exercise physiology
      of cephalopods, which are characterized by high rates of aerobic and anaerobic
      energy turnover during high velocity hunts or escapes in their pelagic
      environment, and a sipunculid worm, which mostly uses anaerobic resources during
      extended marathon-like digging excursions in the hypoxic marine sediment.
      Particular attention is paid to how lifestyle and oxygen availability in various
      marine environments shapes the use and rates of aerobic and anaerobic metabolism
      and acidosis as they depend on activity levels and energy saving strategies.
      Whereas aerobic scope and, accordingly, use of ambient oxygen by blood oxygen
      transport and skin respiration is maximized in some squids, aerobic scope is very
      small in the worm and anaerobic metabolism readily used upon muscular activity.
      Until recently, it was widely accepted that the glycolytic end product octopine,
      produced in the musculature of these invertebrates, acted as a weak acid and so
      did not compromise acid-base balance. However, it has now been demonstrated that
      octopine does cause acidosis. Concomitant study of tissue energy and acid-base
      status allows to evaluate the contribution of glycolysis, pH and free ADP
      accumulation to the use of the phosphagen and to the delayed drop in the Gibb's
      free energy change of ATP hydrolysis. The analysis reveals species specific
      capacities of these mechanisms to support exercise beyond the anaerobic
      threshold. During high intensity anaerobic exercise observed in squid, the levels
      of ATP free energy change finally fall to critical minimum levels contributing to
      fatigue. Maintenance of sufficiently high energy levels is found at low but
      extended rates of anaerobic metabolism as observed in the long term digging
      sipunculid worm. The greatest aerobic and anaerobic performance levels are seen
      in squid inhabiting the open ocean and appear to be made possible by the uniform
      and stable physicochemical parameters (esp. high O(2) and low CO(2) levels) that
      characterize such an environment. It is suggested that at least some squid
      operate at their functional and environmental limits. In extremely different
      environments, both the worm and the squids display a tradeoff between oxygen
      availability, temperature, performance level and also, body size.

PMID- 12208303
TI  - Environmental and genetic influences on flight metabolic rate in the honey bee,
      Apis mellifera.
AB  - Flying honey bees demonstrate highly variable metabolic rates. The lowest
      reported values (approximately 0.3 Wg(-1)) occur in tethered bees generating the
      minimum lift to support their body weight, free-flying 2-day old bees, winter
      bees, or bees flying at high air temperatures (45 degrees C). The highest values
      (approximately 0.8 Wg(-1)) occur in foragers that are heavily loaded or flying in
      low-density air. In different studies, flight metabolic rate has increased,
      decreased, or remained constant with air temperature. Current research
      collectively suggests that this variation occurs because flight metabolic rates
      decrease at thorax temperatures above or below 38 degrees C. At 30 degrees C,
      approximately 30% of colonial energy is spent during typical foraging, so
      variation in flight metabolic rate can strongly affect colony-level energy
      balance. Higher air temperatures tend to increase colonial net gain rates,
      efficiencies and honey storage rates due to lower metabolic rates during flight
      and in the hive. Variation in flight metabolism has a clear genetic basis.
      Different genetic strains of honey bees often differ in flight metabolic rate,
      and these differences in flight physiology can be correlated with foraging
      effort, suggesting a possible pathway for selection effects on flight metabolism.

PMID- 12208304
TI  - Hummingbird foraging and the relation between bioenergetics and behaviour.
AB  - Because of their small size and expensive mode of flight, hummingbirds display
      some of the highest known mass-specific rates of aerobic metabolism among
      vertebrates. High enzymatic flux capacities through pathways of carbohydrate and
      long-chain fatty acid oxidation indicate that either substrate can fuel flight.
      Although hummingbirds are known to rely on fat to fuel migratory flight, short
      foraging bouts are fueled by the oxidation of carbohydrate, not fat. This allows
      birds refueling at meadows during migration to deposit fat at higher rates and
      avoids the energetic inefficiency that results from synthesizing fat from dietary
      sugar, and then breaking down the fat to fuel foraging flight. On cold mornings
      in subalpine meadows, refueling hummingbirds achieve net energy gain despite the
      high energetic costs of thermoregulation and flight. In doing so, they sustain
      the highest known time-averaged metabolic rates among vertebrates. However, low
      sucrose concentrations, provided in volumes large enough to allow the maintenance
      of energy balance at low temperature, result in energy deficit and mass loss. The
      problem of disposing of dietary water at low ambient temperature when intake
      rates are elevated suggests that the kidneys may be involved in establishing the
      upper limit to intake rates and, therefore, maximum sustained metabolic rates. It
      is suggested that hummingbird behaviour and metabolism have coevolved to maximize
      net energy gain. Further, the energetics of hummingbird thermoregulation and
      flight may have influenced the evolution of sucrose content in floral nectar.

PMID- 12208305
TI  - Expression of an uncoupling protein gene homolog in chickens.
AB  - An avian uncoupling protein (UCP) gene homolog was recently sequenced from
      skeletal muscle and was proposed to have a role in thermogenesis in chickens,
      ducks and hummingbirds. Since mammalian UCP 2 and UCP 3 also appear to have
      functions associated with energy and substrate partitioning and body weight
      regulation, the purpose of this study was to further characterize chicken UCP
      under conditions of nutritional stress and/or leptin administration. Male 3-week
      old chickens were starved for 24 or 48 h and then half of each group was refed
      for an additional 24 h. In a follow-up experiment, chickens were fed or starved
      for 48 h with or without leptin administration. Feed deprivation increased UCP
      mRNA expression in skeletal muscle by up to 260% (P<0.001), and in a time
      dependent manner in pectoralis muscle. Refeeding for 24 h normalized muscle UCP
      mRNA levels. Leptin administration had no effect on muscle UCP. Chicken muscle
      UCP mRNA levels were highly correlated with plasma triglyceride and non
      esterified fatty acid (NEFA) concentrations, and with circulating levels of
      insulin, insulin-like growth factor (IGF)-I and IGF-II. These results suggest
      that, as in mammals, avian UCP is up-regulated during feed deprivation and is
      highly correlated with increased fatty acid oxidation and flux into skeletal
      muscle.

PMID- 12208306
TI  - Effect of short-term vs. long-term elevation of dietary protein intake on
      responsiveness of rat thick ascending limbs to peptide hormones.
AB  - We compared the renal responses of rats on three diet regimens. Rats received
      either 8% protein food (low-protein, LP) for 10 weeks following weaning, 8%
      protein for 9 weeks followed by 1 week on 30% protein (short-term high-protein,
      SHP), or 30% protein for 10 weeks (high-protein, HP). Kidneys from HP rats were
      enlarged by approximately 50%, or 20% when corrected for body mass. Most of this
      hypertrophy resulted from enlargement of the inner stripe of the outer medulla,
      site of the thick ascending limbs (TAL), and TAL from HP rats were larger in
      diameter. SHP rats had TAL diameters similar to HP rats, but changes in renal
      mass or height of renal zones did not reach statistical significance. The
      activity of adenylyl cyclase (AC) in TAL, measured from the accumulation of cAMP
      in isolated tubules, increased with dose of both arginine vasopressin (AVP) and
      glucagon in all rats. However, HP rats had significantly higher hormone-induced
      AC activity than LP or SHP rats, which were not different from each other. Our
      results suggest that tubule hypertrophy may precede up-regulation of hormone
      sensitive AC activity during the progression of renal response to elevated
      dietary protein.

PMID- 12208307
TI  - Blood chemistry in southern elephant seal mothers and pups during lactation
      reveals no effect of handling.
AB  - Serum clinical chemistry parameters were examined in lactating southern elephant
      seal Mirounga leonina mothers and their pups from the declining Macquarie Island
      population. There were significant changes in serum values from 2 to 21 days
      postpartum in both nursing mothers (increase: inorganic phosphate; decrease:
      creatinine, potassium, chloride, cholesterol, total protein, albumin, globulin,
      aspartate aminotransferase, creatine kinase) and suckling pups (increase:
      inorganic phosphate, globulin, cholesterol; decrease: albumin, alkaline
      phosphatase, gammaglutamyl transferase; increase followed by decrease:
      triglycerides, iron). We found no evidence that changes were due to chronic
      stress effects caused by repeated chemical immobilisations (mothers) or physical
      restraint (pups): at late lactation, clinical chemistry values were similar for
      mother-pup pairs of a control group (not handled previously), moderate treatment
      group (previously handled twice) and high treatment group (previously handled
      three to four times). We were not able to detect differences in clinical
      chemistry values between mother-pup pairs distributed over two areas differing in
      the frequency of human visits. The clinical chemistry values presented here can
      serve as reference ranges to allow future comparison with other southern elephant
      seal populations to investigate factors, e.g. food limitation, suspected to be
      involved in population declines.

PMID- 12208308
TI  - Intestinal microbial patterns of the common marmoset and rhesus macaque.
AB  - The intestinal microflora of common marmosets and rhesus monkeys were compared by
      enumerating bacteria from the small and large intestines. Rhesus monkeys had a
      consistent microflora pattern manifest by higher concentrations of total and Gram
      negative aerobic and facultatively anaerobic bacteria, as well as aerobic and
      anaerobic Lactobacilli, in the large intestine as compared to the small
      intestine. In contrast, the marmoset microflora were considerably more variable.
      Approximately two-thirds of the marmosets (designated group A) had an overall
      profile that resembled the rhesus monkeys, but they had significantly higher
      concentrations of Gram-negative microflora in their large intestines than the
      rhesus monkeys. The remaining marmosets (group B) had higher concentrations of
      bacteria in the small intestine as compared to the large intestine, with the
      large intestinal concentrations being significantly lower than in the rhesus
      monkeys and group A marmosets. Moreover, the marmosets did not have detectable
      levels of aerobic Lactobacilli, and anaerobic Lactobacilli concentrations were
      significantly lower than in the rhesus macaques. Although it is unknown why
      microflora differ across species, it is likely that evolutionary adaptations in
      anatomy and functioning of the gastrointestinal tract influence the concentration
      and types of bacteria residing as the normal intestinal microflora.

PMID- 12208309
TI  - Effect of season and artificial diet on amino acids and nucleic acids in gonads
      of green sea urchin Strongylocentrotus droebachiensis.
AB  - The content of total and free amino acids (FAA) in green sea urchin
      (Strongylocentrotus droebachiensis) gonads varied with the season and feeding on
      an artificial diet. Glycine was the dominant amino acid in each season
      contributing 12.9-16.6% to the total amino acid (TAA) content, peaking in the
      spring. In the FAA profile, glycine accounted for 30.3-61.4% in different
      seasons. A grain-based artificial diet had noticeable effects on the total and
      FAA compositions of S. droebachiensis. Although, glycine was the dominant amino
      acid in the TAA profile during early harvesting, tyrosine in gonads became more
      dominant on week 9 of feeding. Furthermore, glycine was the dominant amino acid
      in the FAA pool after feeding the artificial diet. The total FAA content in the
      gonads increased significantly (P<0.05) from 20.6 on week 0 to 180.6 mg/g dry
      mass tissue on week 3. There were no significant (P<0.05) changes between week 6
      and week 9. Deoxyribonucleic acid (DNA) content exceeded that of ribonucleic acid
      (RNA) in each season, while in cultured urchins, RNA content exceeded that of DNA
      only on week 6. The RNA/DNA ratio was significantly increased in the summer,
      whereas this ratio was increased up to week 6 followed by a decrease on week 9 in
      cultured counterparts.

PMID- 12208310
TI  - High plasma buffering and the absence of a red blood cell beta-NHE response in
      brown bullhead (Ameiurus nebulosus).
AB  - The high non-bicarbonate buffer capacity of brown bullhead (Ameiurus nebulosus)
      plasma was postulated to function as an alternative mechanism for the protection
      of red blood cell (RBC) intracellular pH (pHi) in the absence or attenuation of a
      RBC adrenergic response. The requirement for protecting RBC pHi arises from the
      presence of a Root effect haemoglobin in bullhead. In support of this hypothesis,
      bullhead RBCs incubated in vitro with isoproterenol (10(-8)-10(-5) mol l(-1)) or
      forskolin (10(-4) mol l(-1)) exhibited significant cyclic AMP accumulation, but
      failed to exhibit cell swelling or significant Na(+) or Cl(-) accumulation;
      plasma pH (pHe) was also unaffected. Similarly, no significant effect on RBC
      water content, Na(+) or Cl(-) concentration, or pHe was detected in bullhead
      blood incubated with 8-bromo cyclic AMP (10(-4)-10(-2) mol l(-1)) in vitro. These
      results suggest that while bullhead RBCs possess a beta-adrenoreceptor linked to
      cyclic AMP formation, stimulation of this adrenergic receptor does not result in
      measurable activation of a Na(+)/H(+) exchanger.

PMID- 12208311
TI  - Lactulose-induced diarrhoea in rats: effects on caecal development and activities
      of microbial enzymes.
AB  - The intake of large amounts of lactulose and other non-digestible
      oligosaccharides can cause diarrhoea in rats and humans. The purpose of our study
      was to estimate tendency and scope of changes in caecum development, amount and
      composition of caecal digesta and activity of caecal microbial enzymes under the
      influence of lactulose-rich diet evoking or not evoking diarrhoea. Male Wistar
      rats were fed on 8%-lactulose diet for 4 weeks. Feeding with lactulose induced
      enlargement of the caecum (digesta and wall) compared to the control group.
      However, the hypertrophy of the caecal wall in rats with diarrhoea was less than
      in these without that ailment. Dry matter of caecal digesta was significantly
      decreased in rats with diarrhoea. Diarrhoea lowered concentrations of enzymatic
      protein and short-chain fatty acids in the caecum, and the activity of bacterial
      beta-glucuronidase, alpha- and beta-galactosidase, alpha- and beta-glucosidase in
      caecal digesta, compared to rats without diarrhoea. The ammonia concentration in
      the caecum was enhanced by diarrhoea symptoms. Occurrence of diarrhoea
      significantly deteriorated functioning of the caecal ecosystem what in turn
      limited potential benefits of diet supplementation with lactulose.

PMID- 12208312
TI  - Effects of the plant alkaloid tetrandrine on human nicotinic acetylcholine
      receptors.
AB  - Functional effects of the well-characterized antagonist of L-type Ca(2+) channels
      tetrandrine on recombinant human gamma-aminobutyric acid type A (GABA(A))
      (alpha1beta2gamma2s) receptor or human alpha7, alpha4beta2, alpha1beta1deltagamma
      and alpha1beta1delta epsilon nicotinic acetylcholine receptors expressed in
      Xenopus oocytes were examined using two-electrode voltage clamp. Tetrandrine
      inhibited the function of acetylcholine nicotinic receptors, but it had no effect
      on GABA(A) receptors. Potency of inhibition was influenced by the receptor
      subtype and the rank order was alpha4beta2>alpha7>alpha1beta1deltagamma congruent
      with alpha1beta1delta epsilon. Functional inhibition of alpha4beta2 and
      alpha1beta1deltagamma receptors was noncompetitive, but only inhibition of
      alpha1beta1deltagamma receptors was voltage-dependent. Binding of 125I-alpha
      bungarotoxin to alpha1beta1deltagamma or 3H-cytisine to alpha4beta2 receptors was
      also inhibited by tetrandrine, but inhibition was noncompetitive and required
      concentrations higher than those needed to inhibit receptor function. Inhibition
      of both alpha7 receptor function and binding of 125I-alpha-bungarotoxin to alpha7
      receptor were mixed competitive/noncompetitive and occurred at a similar
      concentration range.

PMID- 12208313
TI  - Photoisomerization of fluvoxamine generates an isomer that has reduced activity
      on the 5-hydroxytryptamine transporter and does not affect cell proliferation.
AB  - Fluvoxamine, a selective serotonin re-uptake inhibitor, is used as
      antidepressant/anxiolytic. The presence of a C=N double bond in the structure of
      fluvoxamine implies the existence of two geometric isomers: E- (trans) and Z-
      (cis), and suggests the hypothetical susceptibility of the molecule to
      photoisomerization. Clinically effective fluvoxamine is in its trans form. UVB
      (ultraviolet light, class B, wavelength range 290-320 nm) irradiation of aqueous
      solutions of fluvoxamine generated a photoproduct, which was isolated and
      analyzed by nuclear magnetic resonance (NMR) and mass spectrometry (MS), and
      identified as the cis isomer of fluvoxamine. This cis-isomer lost capacity to
      inhibit serotonin uptake, suggesting that light exposure might reduce the
      clinical efficacy of fluvoxamine. Alternatively, the photoproduct could be used
      as an inactive isomer in the studies of antidepressant mechanisms. Recent
      proposal suggests that antidepressants increase neurogenesis in the adult brain,
      whereas either an inhibitory or a stimulatory action of antidepressants on
      [(3)H]thymidine uptake in vitro has been attributed to their interaction with
      serotonergic mechanisms. Lower concentrations (i.e., 2 microM) of fluvoxamine and
      fluoxetine (another selective serotonin re-uptake inhibitor) stimulated
      [(3)H]thymidine uptake in mature, but inhibited it in immature cultures of rat
      cerebellar granule cells; the photoproduct was ineffective. A high concentration
      of fluvoxamine (i.e., 20 microM) but not the photoproduct was toxic to both
      immature and mature cultures. We suggest that a mechanism sensitive to
      fluvoxamine photoisomerization might be involved in the action of antidepressants
      on cell proliferation.

PMID- 12208314
TI  - Suppression of cytotoxin-induced cell death in isolated hepatocytes by tea
      catechins.
AB  - To elucidate the hepatoprotective effects of green tea catechins, the following
      experiments were conducted utilizing (-)-epigallocatechin-3-gallate (EGCG), the
      major component of green tea catechin, together with other catechins. The
      protective effects of catechins against hepatotoxins, bromobenzene or rubratoxin
      B, were examined in primary cultures of rat hepatocytes. Bromobenzene and
      rubratoxin B are known to induce necrosis and apoptosis of cells, respectively.
      After 24-h treatment with toxin, EGCG and (-)-epigallocatechin-3-(3"-O
      methyl)gallate (EGCg-3"-OMe) suppressed the bromobenzene-induced morphological
      change and dose-dependently prevented bromobenzene-induced cell death. Both
      catechins also prevented apoptotic cell death caused by rubratoxin B. In
      rubratoxin B-treated cells, both catechins were found to suppress the activation
      of caspase-3 by rubratoxin B. The results in the present study suggest that EGCG
      and EGCg-3"-OMe are potent hepatoprotective agents. This report is the first to
      show that catechins suppress cytotoxin-induced cell death.

PMID- 12208315
TI  - The calcitonin receptor-like receptor/receptor activity-modifying protein 1
      heterodimer can function as a calcitonin gene-related peptide-(8-37)-sensitive
      adrenomedullin receptor.
AB  - The receptor activity-modifying protein (RAMP)/calcitonin receptor-like (CRL)
      receptor heterodimer is thought to function as a receptor for either a calcitonin
      gene-related peptide (CGRP) (CRL receptor/RAMP1) or adrenomedullin (CRL
      receptor/RAMP2 or -3), depending on the RAMP isoform present. We examined the
      receptor specificity of adrenomedullin-induced increases in cAMP in human
      embryonic kidney (HEK)293 cells coexpressing human CRL receptor and human RAMP1
      or RAMP2. In cells expressing CRL receptor/RAMP1, adrenomedulin-induced increases
      in cAMP were comparable to those induced by alpha-CGRP, and the CGRP receptor
      antagonist alpha-CGRP-(8-37), but not the adrenomedullin receptor antagonist
      adrenomedullin-(22-52), blocked the adrenomedullin-evoked responses. Cells
      expressing CRL receptor/RAMP2 responded more selectively to adrenomedullin; in
      this case, the effect was blocked by adrenomedullin-(22-52) but not by alpha-CGRP
      (8-37). Real-time quantitative polymerase chain reaction confirmed that
      cotransfection of CRL receptor and RAMP1 had no effect on the endogenous
      expression of RAMP2. Thus, CRL receptor/RAMP1 likely functions as an
      adrenomedullin receptor as well as a CGRP receptor, which may explain why many of
      the actions of adrenomedullin are potently antagonized by alpha-CGRP-(8-37).

PMID- 12208316
TI  - Preprotachykinin A gene expression after administration of 3,4-methylene
      dioxymethamphetamine (Ecstasy).
AB  - This study tested the effects of 8 days of subchronic administration of 3,4
      methylene dioxymethamphetamine (MDMA) (5 mg/kg b.w.) on preprotachykinin A mRNA
      levels in discrete rat brain regions. In situ hybridization examined
      preprotachykinin A mRNA levels in the core and shell of the nucleus accumbens,
      the islands of Calleja, the olfactory tubercle, the dorsal and ventral caudate
      putamen, the bed nucleus of the stria terminalis, the medial preoptic area, the
      medial habenular nucleus and in the postero-dorsal part of the medial amygdala.
      Higher levels of preprotachykinin A mRNA were found in the core and shell of the
      nucleus accumbens, in the islands of calleja, in the olfactory tubercle, in the
      bed nucleus of the stria terminalis, in the medial habenular nucleus and the
      postero-dorsal part of the medial amygdala, compared to control animals.
      Conversely, increased preprotachykinin A mRNA levels were observed in the dorsal
      and ventral caudate-putamen in MDMA treated when compared to control rats. In the
      social memory test, MDMA significantly impaired rats' short-term working memory.
      These results show that chronic exposure to MDMA strongly affects
      preprotachykinin A mRNA levels in discrete rat brain regions. These changes occur
      in experimental conditions in which working memory is markedly reduced,
      suggesting that changes in gene expression of tachykinin mechanisms may
      contribute to the effects of MDMA on memory function.

PMID- 12208317
TI  - SCH 58261 differentially influences quinolinic acid-induced effects in striatal
      and in hippocampal slices.
AB  - The influence of the adenosine A(2A) receptor antagonist SCH 58261 (7-(2
      phenylethyl)-5-amino-2-(2-furyl)-pyrazolo-[4,3-e]-1,2,4-trizolo[1,5-c]
      pyrimidine) (50, 200 nM, 1 microM) on quinolinic acid effects has been studied in
      rat striatal and hippocampal slices. Quinolinic acid induced disappearance of
      field potentials at concentrations of 500 microM and 2 mM in hippocampal and
      corticostriatal slices, respectively. We found that 1 microM SCH 58261 prevented
      quinolinic acid-induced field potential disappearance in corticostriatal but not
      in hippocampal slices. This finding demonstrates that the peculiar binding
      profile of SCH 58261 and the predominance in the hippocampus of "atypical"
      adenosine A(2A) receptor population (not recognized by SCH 58261) could have a
      functional relevance in the occurrence of region-specific neuroprotective
      effects.

PMID- 12208318
TI  - Effects of nimesulide on nitric oxide-induced hyperalgesia in humans--a
      neurophysiological study.
AB  - Nonsteroidal anti-inflammatory drugs (NSAIDs) are known to induce analgesia
      mainly via the inhibition of cyclo-oxygenase. Several reports suggest that
      chronic pain is mediated by central sensitization, an N-methyl-D-aspartate (NMDA)
      mediated phenomenon influenced by cyclo-oxygenase activity and nitric oxide (NO).
      In this double-blind study, we evaluated the effects of a preferential inhibitor
      of the inducible isoform of cyclo-oxygenase-2, nimesulide, on the spinal
      nociceptive flexion reflex (RIII reflex) before and after administration of an NO
      donor in healthy volunteers. Nimesulide caused a reduction of the RIII reflex
      area, which persisted after NO donor administration. Conversely, in the placebo
      group the RIII reflex area significantly increased following the administration
      of the NO donor. These data suggest a central effect for nimesulide, possibly
      related to a reduction of nociceptive activity at spinal level.

PMID- 12208319
TI  - Regional hemodynamic effects of nociceptin/orphanin FQ in the anesthetized rat.
AB  - This study examined the vasodilator action of nociceptin, an endogenous opioid
      receptor-like ligand (ORL1), in thiobutabarbital-anesthetized rats, via the
      triple-isotope microspheres technique. Nociceptin (10, 30 nmol/kg, left
      ventricular injection) reduced mean arterial pressure (-27, -29 mm Hg), total
      peripheral resistance (-36, -41% of baseline) and heart rate (-8, -11% of
      baseline), but did not significantly affect cardiac output. The vehicle (0.9%
      NaCl) did not alter hemodynamics. Both doses of nociceptin caused similar changes
      in arterial flow and conductance of all tissues. Nociceptin increased flows to
      the skeletal muscle, slightly reduced flows to the caecum and colon, but did not
      alter flows to other organs and tissues. With flow normalized by pressure to
      reflect intrinsic vascular tone, nociceptin was found to increase arterial
      conductance of all tissues, except for the intestine, spleen, caecum and colon.
      Its dilator influence was greater in the skeletal muscle ( approximately 250% of
      baseline conductance) than the lungs, heart, liver, stomach, kidneys, skin,
      testes and brain (140-160% of baseline). Thus, nociceptin causes generalized
      vasodilatation; its greatest influence is on the skeletal muscle bed.

PMID- 12208320
TI  - A putative role for S-nitrosoglutathione as the source of nitric oxide in
      photorelaxation of the mouse gastric fundus.
AB  - Mouse gastric fundus strips were relaxed by ultraviolet light (UV) irradiation,
      exogenous nitric oxide (NO), isoproterenol, S-nitrosoglutathione, S-nitroso-L
      cysteine and S-nitroso-N-acetyl-penicillamine. Glutathione did not affect
      relaxations in response to UV irradiation, exogenous NO and isoproterenol while
      inhibiting that with S-nitrosoglutathione. L-Cysteine inhibited responses to UV
      irradiation and exogenous NO, but not in the presence of exogenous Cu(2+)/Zn(2+)
      superoxide dismutase. However, L-cysteine alone or in combination with
      Cu(2+)/Zn(2+) superoxide dismutase did not affect the relaxations in response to
      S-nitroso-L-cysteine. Ethacrynic acid and diamide inhibited photorelaxations but
      not the relaxations with exogenous NO and isoproterenol. This inhibition was
      prevented by glutathione, but not by L-cysteine. S-nitrosoglutathione-induced
      relaxations were abolished by diamide and ethacrynic acid, whereas responses to S
      nitroso-L-cysteine and S-nitroso-N-acetyl-penicillamine were only inhibited by
      ethacrynic acid. These results suggest that S-nitrosoglutathione may, at least in
      part, be the putative S-nitrosothiol, which is converted to NO in response to UV
      irradiation in mouse gastric fundus strips.

PMID- 12208321
TI  - Azithromycin modulates neutrophil function and circulating inflammatory mediators
      in healthy human subjects.
AB  - Effects on human neutrophils and circulating inflammatory mediators were studied
      in 12 volunteers who received azithromycin (500 mg/day, p.o.) for 3 days. Blood
      was taken 1 h before treatment, 2.5, 24 h and 28 days after the last dose. An
      initial neutrophil degranulating effect of azithromycin was reflected in rapid
      decreases in azurophilic granule enzyme activities in cells and corresponding
      increases in serum. The oxidative response to a particulate stimulus was also
      acutely enhanced. These actions were associated with high plasma and neutrophil
      drug concentrations. A continuous fall in chemokine and interleukin-6 serum
      concentrations, within the non-pathological range, accompanied a delayed down
      regulation of the oxidative burst and an increase in apoptosis of neutrophils up
      to 28 days after the last azithromycin dose. Neutrophils isolated from blood at
      this time point still contained detectable drug concentrations. Acute neutrophil
      stimulation could facilitate antibacterial effects of azithromycin, while
      delayed, potentially anti-inflammatory activity may curtail deleterious
      inflammation.

PMID- 12208322
TI  - Mystixin peptides reduce hyaluronan deposition and edema formation.
AB  - Hyaluronan and its associated water of hydration are the basis of the swelling
      and edema of acute inflammation. Mystixins are small, synthetic peptides that
      suppress the acute inflammatory response. Mystixin-7, a prototype of these
      peptides, has the structure p-anisoyl-Arg-Lys-Leu-Leu-D-Thi-Ile-D-Leu-NH(2). As
      shown previously by this laboratory, the mystixin-7 peptide inhibits edema
      formation in vivo following intravenous administration at doses of less than 1.0
      mg/kg. Mechanisms by which this peptide might suppress edema were examined here
      in vitro using cultured cells. Normal human dermal fibroblasts normally secrete
      large quantities of hyaluronan in response to inflammatory stimuli. Mystixin-7
      reduced hyaluronan deposition by up to 80% in such cultures. Stimulation of
      hyaluronidase activity was observed. Mystixins represent a novel class of anti
      inflammatory peptides that suppress the edema associated with inflammation. We
      propose that stimulation of hyaluronidase activity, with a decrease in net
      hyaluronan deposition and its associated water of hydration, is among the
      mechanisms of the anti-inflammatory effect of mystixin peptides.

PMID- 12208323
TI  - Viability of microvascular endothelial cells to direct exposure of formalin,
      lambda-carrageenan, and complete Freund's adjuvant.
AB  - We investigated three inflammatory agents to establish if these substances elicit
      a direct effect on the functional and structural integrity of the blood-brain
      barrier. Cellular cytotoxicity and paracellular permeability were assessed in
      vitro using primary bovine brain microvascular endothelial cells exposed to
      formalin, lambda-carrageenan, or complete Freund's adjuvant for 1, 3, or 72 h,
      respectively. Results showed that only the highest concentration (0.025%) of
      formalin produced a decrease in cell viability (approximately 34%) and a
      significant increase in cell permeability to [(14)C]sucrose at 120 min
      (approximately 137%). Brain perfusion using female Sprague-Dawley rats showed no
      difference in paracellular permeability to [(14)C]sucrose for any inflammatory
      agent. Western blot analyses were performed on isolated rat brain microvessels to
      assess the structural integrity of blood-brain barrier tight junctions. Results
      indicate that expression of zonula occludens-1, occludin, claudin-1, and actin
      remain unchanged following intravenous exposure to inflammatory agents. This
      study confirms that changes seen at the blood-brain barrier following a
      peripheral inflammation are due to physiological responses to the given
      inflammatory agent and not to any direct interaction between the inflammatory
      agent and the brain microvasculature.

PMID- 12208324
TI  - Differentiation of breast masses using 3-D sonographic and echo-enhancer-based
      evaluation of the vascular pattern: initial experiences.
AB  - To evaluate the potential of combined 3-D B-mode and color Doppler (CD) data sets
      in the differentiation of breast masses, in 50 patients with histologically
      proven solid breast lesions, 3-D datasets were acquired. A 3-D display was
      created and volume calculation of tumors, their periphery and vasculature was
      performed. Time-intensity curves of enhancement after administration of a
      contrast agent were analyzed. Volumetry of tumor vasculature yielded no
      significant differences between malignant and benign tumors regarding
      vascularization of the center (2.60 vs. 2.88%) and periphery (6.66 vs. 3.78%).
      Only the mean values for the rise time in the center of the tumor, fibroadenoma
      (FA): 5.7 s and ductal invasive carcinoma (DIC): 15.8s; p = 0.05, and the time to
      peak in the periphery, FA: 21.0 s and DIC: 31.6 s; p = 0.03, differed
      significantly. The 3-D ultrasound (US) technique was of no additional value in
      differentiating breast masses. The calculation of time-intensity curves after
      administration of a contrast agent may be helpful in differentiating FA and DIC.

PMID- 12208325
TI  - Prenatal diagnosis of fetal multicystic dysplastic kidney with two-dimensional
      and three-dimensional ultrasound.
AB  - Fetal multicystic dysplastic kidney (MCDK) may have grave prognosis and prenatal
      diagnosis of MCDK by ultrasound (US) is very important. Traditionally, MCDK is
      diagnosed by 2-D US. Recently, 3-D US has emerged, and may overcome the weakness
      of 2-D US. In this series, we retrospectively analysed the cases of MCDK
      diagnosed by prenatal 2-D and 3-D US from November 1995 to March 2002 to evaluate
      the prenatal sonographic characteristics of this disease and to compare the
      efficacy of 2-D and 3-D US. The 2-D assessment included the lesion of MCDK, the
      amniotic fluid volume and associated anomalies. The 3-D assessment included three
      orthogonal multiplanar views and various rendering modes of reconstruction of
      MCDK. In total, 28 cases were diagnosed by prenatal 2-D and 3-D US. Within the
      study period, 2-D US detected 100% of MCDK, as did 3-D US, and revealed that
      left, right and bilateral MCDK were in 46.4%, 28.6%, and 25% of cases,
      respectively. Oligohydromnios was present in 6 cases (21.4%). In addition, 3-D US
      showed fetal MCDK vividly and provided a whole view of the disease that assisted
      comprehension of the severity and extent better than 2-D US. In conclusion,
      although 2-D US detected all the cases of fetal MCDK in utero as did 3-D US, the
      3-D images generated by various rendering modes can further assist in evaluating
      the severity and extent of MCDK, with a novel view that substantially aids the
      medical team in prenatal management and the parents in genetic consultation.

PMID- 12208326
TI  - Assessment of normal fetal upper arm volume by three-dimensional ultrasound.
AB  - Fetal upper arm volume (UAV) is closely related to fetal growth and nutrition
      status. In the past, 2-D ultrasound (US) has shown limitations in assessing fetal
      UAV. With the recent advancement of 3-D US, the limitation in assessing fetal UAV
      by 2-D US can be overcome. To establish a reference chart of fetal UAV for
      clinical use, a prospective and cross-sectional study using 3-D US was undertaken
      to assess the fetal UAV in normal pregnancy. In total, 206 singleton fetuses
      ranging between 20 and 40 weeks of gestation that fit the criteria of normal
      pregnancies were enrolled in this study. Our results showed that fetal UAV is
      highly correlated with the gestational age. Furthermore, using gestational age
      (GA) as the independent variable and UAV as the dependent variable, the best-fit
      regression equation was UAV (mL) = 43.546 - 4.530 x GA + 0.133 x GA(2) (r =
      0.913, n = 206, p < 0.0001). For further clinical use, a chart of normal growth
      centiles of fetal UAV in utero was then calculated based on this equation. In
      conclusion, we believe our data of fetal UAV assessed by 3-D US can serve as a
      useful reference in evaluating fetal growth and nutrition status during
      gestation.

PMID- 12208327
TI  - The ureteric jet doppler waveform as an indicator of vesicoureteric sphincter
      function in adults and children. An observational study.
AB  - The nature of the action of the vesicoureteric junction (VUJ) in humans is still
      controversial. We were interested in the reasons why the jet consists of several
      peaks. We hypothesised that the modification of the jet into a variable number of
      peaks is the result of an active sphincter mechanism at the VUJ. A total of 1,010
      subjects of all ages and both genders were recruited into this study. The Doppler
      waveform of the jet was recorded bilaterally. We could identify six basic
      patterns of ureteric jet according to the number of peaks: monophasic, biphasic,
      triphasic, polyphasic (four or more peaks), square and continuous. By analysing
      the duration, maximum peak velocity and initial slope of the first four patterns,
      a mechanism of action of an active VUJ sphincter could be postulated.
      Furthermore, the basic patterns could be assigned to three modes of ureteric
      actions: the square and continuous are only seen during diuretic stress; the
      biphasic, triphasic and polyphasic patterns are variations of the adult
      physiological steady-state mode, and the monophasic is distinctly different and
      represents the immature mode.

PMID- 12208328
TI  - Immature ureteric jet doppler patterns and urinary tract infection and
      vesicoureteric reflux in children.
AB  - The Doppler waveform of the ureteric jet is the result of modification of
      ureteric peristalsis by an active sphincteric mechanism of the vesicoureteric
      junction (VUJ). The monophasic pattern is associated with immaturity. This study
      set out to see the correlation between this immature pattern with urinary tract
      infection (UTI) and vesicoureteric reflux (VUR) in children. Ureteric jets of 241
      healthy children and 98 children with UTI were studied. The monophasic pattern
      was found in 29% of healthy children overall, but varied greatly according to
      age. The monophasic pattern was virtually universal in the first 6 months of
      life, dropping to below 15% in late childhood. This immature pattern was more
      commonly seen in the UTI (73.5%) and VUR (90.5%) groups than in the healthy
      controls. The difference was statistically significant (p = 0.0005 for both). The
      persistence of this immature pattern was highly associated with UTI and VUR.

PMID- 12208329
TI  - Doppler waveform of the ureteric jet in pregnancy.
AB  - We have shown that the function of the bladder vesicoureteric junction (VUJ) can
      be studied by the Doppler waveform of the ureteric jet, and this reflects the
      active sphincteric mechanism of the VUJ. We wished to investigate if the hormonal
      changes of pregnancy cause any alteration of VUJ function. A total of 107
      pregnant women and 375 nonpregnant women were recruited. Three scans, 20 and 32
      weeks of gestational age and 3 months postpartum, were done. The occurrence of a
      monophasic waveform in the nonpregnant group was 1.9%. In the pregnancy group,
      this was 18.7%, 41.1% and 1.6% at 20, 32 weeks of gestational age and 3 months
      postpartum, respectively. The difference in occurrence of the monophasic
      waveforms was statistically significant (both p = 0.0005 at 20 and 32 weeks).
      This suggests an adverse hormonal effect on the vesicoureteric junction during
      pregnancy, and may be a factor in the increased risk of UTI in pregnancy.

PMID- 12208330
TI  - Ureteric jet in renal transplantation patient.
AB  - We have made a case for an active sphincteric mechanism at the VUJ modifying the
      ureteric jet Doppler waveform. The transplanted ureter does not have a normal
      VUJ, but retains inherent peristalsis. This study was to document any difference
      in the transplanted ureteric jet Doppler pattern. A total of 55 transplant
      patients and 817 healthy subjects were recruited. The Doppler waveform of the
      transplanted ureter is distinctly different from that of the healthy adult
      ureter. There are two major patterns: a short monophasic waveform is the most
      common (66.1% vs. 2.6% in healthy ureters). Less common is a longer, more phasic,
      pattern, which, however, does not resemble the patterns of the healthy ureter.
      This supports the hypothesis that the mode of action at the VUJ is sphincteric,
      because this is lost with transplantation, and ureteric drainage reverts to a
      simple unmodified pattern.

PMID- 12208331
TI  - Assessment of menopause-induced myocardial changes by integrated backscatter
      during inotropic stimulation and atropine injection.
AB  - Estradiol has been considered as an L-type calcium channel blocker in animal
      studies. The concentration of estradiol decreases after menopause. Therefore, we
      hypothesized that human myocardial functional changes developed after menopause,
      and those changes could be evaluated through the use of cyclic variation of
      integrated backscatter (CVIBS). A total of 16 patients with menopause (native and
      surgical menopause), follicular stimulating hormone > 40 IU/L and estradiol < 20
      pg/mL underwent dobutamine stress IBS examination (study group). Another 12 women
      with normal menstruation, follicular stimulating hormone < 40 IU/L and estradiol
      > 20 pg/mL were enrolled as a control group. All patients had a low likelihood of
      coronary artery disease and negative results of dobutamine stress
      echocardiography and (201)thallium scintigraphy. To avoid the phenomenon of
      anisotropy, the amplitude and phase of IBS were acquired only in the
      midanteroseptal segment from the parasternal short axis view. The baseline
      amplitudes of CVIBS differed between the control and study groups (5.9 +/- 1.2 dB
      vs. 8.1 +/- 2.1 dB; p = 0.007). The amplitudes during low-dose (20 microg/kg-min)
      and peak-dose (40 microg/kg-min) dobutamine infusion were also different between
      these 2 groups (5.7 +/- 0.9 dB vs. 8.4 +/- 1.7 dB; p < 0.001; 6.0 +/- 1.0 dB vs.
      7.7 +/- 2.4 dB; p = 0.026). However, there were no significant differences in
      amplitudes between these two groups after atropine injection (control group 4.5
      +/- 1.2 dB, study group 5.3 +/- 1.0 dB; p = NS). No significant differences of
      phase were found either at baseline or under dobutamine infusion between the two
      groups. Multivariate linear regression analysis showed that only menopause status
      associated significantly with the amplitudes at different doses of dobutamine
      infusion (p < 0.05). In conclusion, human myocardial functional changes are
      observed by CVIBS after menopause. Postmenopausal women have higher values of
      amplitude than premenopausal women. These phenomena persist during low and peak
      doses of dobutamine infusion, but are abolished by atropine injection.

PMID- 12208332
TI  - Use of the bootstrap technique with small training sets for computer-aided
      diagnosis in breast ultrasound.
AB  - The purpose of this study was to test the efficacy of using small training sets
      in computer-aided diagnostic systems (CAD) and to increase the capabilities of
      ultrasound (US) technology in the differential diagnosis of solid breast tumors.
      A total of 263 sonographic images of solid breast nodules, including 129
      malignancies and 134 benign nodules, were evaluated by using a bootstrap
      technique with 10 original training samples. Texture parameters of a region-of
      interest (ROI) were resampled with a bootstrap technique and a decision-tree
      model was used to classify the tumor as benign or malignant. The accuracy was
      87.07% (229 of 263 tumors), the sensitivity was 95.35% (123 of 129), the
      specificity was 79.10% (106 of 134), the positive predictive value was 81.46%
      (123 of 151), and the negative predictive value was 94.64% (106 of 112). This
      analysis method provides a second opinion for physicians with high accuracy. The
      new method shows a potential to be useful in future application of CAD,
      especially when a large database cannot be obtained for training or a newly
      developed ultrasonic system has smaller sets of samples.

PMID- 12208333
TI  - Retrieval technique for the diagnosis of solid breast tumors on sonogram.
AB  - We evaluated a series of pathologically proven breast tumors using an image
      retrieval technique for classifying benign and malignant lesions. A total of 263
      breast tumors (129 malignant and 134 benign) were retrospectively evaluated. The
      physician located regions-of-interest (ROI) of ultrasonic images and texture
      parameters (contrast, covariance and dissimilarity) were used in the process of
      the content-based image-retrieval technique. The accuracy of using the retrieval
      technique for classifying malignancies was 92.55% (236 of 255), the sensitivity
      was 94.44% (119 of 126), the specificity was 90.70% (117 of 129), the positive
      predictive value was 90.84% (119 of 131), and negative predictive value was
      94.35% (117 of 124) for the proposed computer-aided diagnostic system. This
      computer-aided diagnosis system can provide a useful tool and its high negative
      predictive value could potentially help avert benign biopsies. It is unnecessary
      to perform any training procedures. This computer-aided diagnosis system can
      provide a second opinion for a sonographic interpreter; the main advantage in
      this proposed system is that we do not need any training. Historical cases can be
      directly added into the database and training of the diagnosis system again is
      not needed. With the growth of the database, more and more information can be
      collected and used as reference cases while performing diagnoses. This increases
      the flexibility of our diagnostic system.

PMID- 12208334
TI  - A comparison of brachial artery reactivity measured by external and intravascular
      ultrasound.
AB  - External ultrasound (US), EXUS, is widely used to measure brachial artery (BA)
      diameter changes in the assessment of vascular function; however, it has not been
      compared with other imaging modalities. We simultaneously measured BA diameter
      responses to hyperaemic flow and nitrate using EXUS and intravascular ultrasound
      (US), IVUS, in 10 patients. Mean diameters measured across all time periods
      correlated closely (r = 0.67, p < 0.001). Percent diameter change to hyperaemia
      and nitrate also correlated well (r = 0.67, p < 0.01). IVUS cross-sectional area
      (CSA) was significantly different from that calculated from EXUS using pir(2)
      (23.95 +/- 4.89 vs. 20.35 +/- 4.51 mm(2), respectively, p < 0.001). Orthogonal
      diameters measured by IVUS were significantly different (5.45 +/- 0.85 vs. 5.17
      +/- 0.79 mm, respectively, p < 0.005). In conclusion, EXUS and IVUS BA diameter
      measurements correlated well; however, discrepancies in absolute measurements
      were revealed. The cross-section of the BA is oval; therefore, deriving CSA by
      pir(2) is inaccurate.

PMID- 12208335
TI  - The influence of brightness, colour and complexity on visual evoked doppler flow
      responses.
AB  - The purpose of this study was to evaluate specific influence of colour,
      brightness and complexity on visual evoked flow responses (VEFRs). A total of 31
      healthy subjects aged 35.1 +/- 7.7 years participated in the study. Mean arterial
      velocity was measured in the right posterior cerebral artery (v(pca)) and in the
      left middle cerebral artery (v(mca)) by Multi-DopX4 (DWL). Simple-white (SW), red
      (R) and complex-checkerboard (C) stimuli were used. VEFRs were determined by the
      difference of the v(pca):v(mca) ratio before and after stimulation. The VEFRs of
      SW with brightness of 21.4 cd/m(2), 10.5 cd/m(2) and 2 cd/m(2) were 8.7 +/- 3.4%,
      9.1 +/- 3.0% and 8.0 +/- 3.7%, respectively (p < 0.001). The VEFRs of R and C
      stimuli were 10.4 +/- 6.5% and 12.4 +/- 6.1%, respectively (p < 0.001). ANOVA for
      repeated measurements did not show significant variances (p = 0.295) between
      VEFRs of SW of different brightness, but variances between VEFRs of SW, R and C
      stimuli were significant (p < 0.001). We found significant differences between
      VEFRs of SW and of C stimuli (3.8 +/- 1.9%, p < 0.001), VEFRs of SW and of R
      stimuli (1.8 +/- 2.4%, p = 0.008) as well as between VEFRs of C and of R stimuli
      (2.0 +/- 2.5%, p = 0.010). We have concluded that SW, R and C stimuli have a
      specific influence on VEFRs. Brightness does not appear to affect VEFRs.

PMID- 12208336
TI  - Real-time rectilinear volumetric imaging using a periodic array.
AB  - Current real-time phased array volumetric scanners use a 2-D array to scan a
      pyramidal volume comprised of many sector scans stacked in the elevation
      direction. This scan format is primarily useful for cardiac imaging to avoid
      interference from the ribs. However, a real-time rectilinear volumetric scan with
      a wider field-of-view (FOV) close to the transducer could prove more useful for
      abdominal, breast or vascular imaging. In our previous work, a 94 x 94 Mills
      cross array operating at 5 MHz was fabricated, and the first real-time
      rectilinear volumetric images were made using a 2-D array and the Duke real-time
      3-D scanner. The FOV for the Mills cross was 30 x 8 x 60 mm. Despite reasonable
      success with the Mills cross array, the array had limitations of poor off-axis
      sensitivity and a smaller FOV in one direction. To overcome these limitations, a
      new rectilinear array containing over 65,500 elements was developed with a
      periodic geometry to increase the FOV to 30 mm x 30 mm x 60 mm and improve the
      off-axis sensitivity. Images of tissue-mimicking phantoms and the carotid artery
      in vivo were obtained. In addition, spectral and color flow Doppler results from
      a pulsatile flow phantom were obtained.

PMID- 12208337
TI  - Acoustic inhomogeneity of carotid arterial plaques determined by GHz frequency
      range acoustic microscopy.
AB  - Characterization of the structure and composition of carotid arterial plaques is
      important to predict the risk of embolic and thrombotic events. In clinical
      echography, echolucent lesions seem to be more associated with stroke than
      echogenic lesions, and a low grey-scale median is associated with a fivefold
      increase in the incidence of silent infarcts. In the present study, five fixed
      human carotid atherosclerotic lesions were observed by GHz-range scanning
      acoustic microscopy (SAM). The atherosclerotic lesions were characterized by
      either thickened fibrosis with dense collagen fibers or lipid accumulation with
      sparse collagen network by optical microscopy. SAM revealed that the fibrosis was
      classified into type I and III collagen by attenuation of ultrasound (US) and
      that the sound field of lipid accumulation lesions became inhomogeneous. The
      results would provide the scientific basis for the images of vulnerable plaques
      being produced in diagnostic US.

PMID- 12208338
TI  - High-frequency ultrasound imaging of the intervertebral disc.
AB  - In vitro investigation of the detailed structure of the intervertebral disc has
      been reliant upon microdissection and histological techniques. However, these
      techniques are laborious and destructive; the latter aspect is important because
      it precludes repetitive testing of the disc during in vitro experimentation. The
      aim of the present study was to investigate the potential of using scanning
      acoustic microscopy (SAM) to image the detailed structure of the intact disc. A
      mechanically scanned 46-MHz transducer operating in pulse-echo mode was used to
      obtain images of porcine coccygeal and lumbar discs; scanned regions-of-interest
      (ROIs) were marked using permanent dye and small surface cuts, respectively. SAM
      images were compared with corresponding images obtained using conventional
      histological techniques. The annulus fibrosus was characterised by alternate
      light and dark bands; the former represent the boundary between adjacent
      lamellae. Lamellar discontinuities and pathologic abnormalities were observed in
      specimens. SAM is a novel, nondestructive method for detailed visualisation of
      the internal structure of the disc in vitro.

PMID- 12208339
TI  - Endothelial cell injury in venule and capillary induced by contrast
      ultrasonography.
AB  - The aim of the present study was to test the hypothesis that microvascular
      endothelial cells (EC) are subject to the bioeffects induced by contrast
      ultrasound (US) because of their proximity to the circulating microbubbles. We
      examined EC injury in each microvessel section (arteriole, capillary or venule)
      in rat mesenteries among the following five groups: three controls (sham
      operation, microbubble injection alone, US exposure with saline injection), and
      two contrast-US groups (US exposure at a 1-Hz or 30-Hz frame rate with
      microbubble injection). Propidium iodide (PI), a fluorescent indicator of cell
      injury, was employed to visualize impaired EC. PI-positive nuclei were equally
      few among the three controls. Contrast-US increased PI-positive cells in
      capillaries (1-Hz frame rate, 2.4 +/- 2.2 cells per 0.1-mm vessel length, p =
      0.09; 30-Hz frame rate, 4.3 +/- 1.8 cells, p < 0.01) and in venules (1-Hz frame
      rate, 4.1 +/- 2.5 cells, p < 0.05; 30-Hz frame rate, 13.8 +/- 3.6 cells, p <
      0.01) compared with sham operation (0.10 +/- 0.22 cells). The finding indicates
      that diagnostic contrast US potentially causes EC injury, particularly in venules
      and capillaries.

PMID- 12208340
TI  - Combined shock-wave and immunogene therapy of mouse melanoma and renal carcinoma
      tumors.
AB  - The effects of ultrasonic shock waves (SW), recombinant interleukin-12 (rIL-12)
      protein and DNA plasmids coding for interleukin-12 (pIL-12) were investigated on
      progression of mouse B16 melanoma and RENCA renal carcinoma tumors. Tumor cells
      were implanted and grown on the hind legs of syngeneic mice. Before treatment,
      mice were anesthetized and the tumor region was shaved and depilated. Air bubbles
      at 10% of tumor volume and an equal volume of phosphate buffered saline (PBS),
      either with rIL-12 or pIL-12 were injected into the tumor. SW treatment consisted
      of 500 SWs (7.4-MPa peak negative pressure) from a spark-gap lithotripter. Tumor
      volume was measured every other day and tumor growth was statistically modeled.
      SW treatment augmented by air injection induced a tumor growth delay for a few
      days immediately after exposure. Intratumor rIL-12 injection enhanced the SW
      effect on tumor progression, to the extent that a statistically significant
      increase in survival was realized in both tumor models. pIL-12 injection alone,
      which is known to produce some gene transfer, provided no detectable tumor-growth
      reduction. The combination of SW and pIL-12 injection provided a statistically
      significant reduction in tumor growth relative to SW alone for both tumor models.
      IL-12 expression due to SW-induced gene transfer was confirmed in ELISA assays.
      This research demonstrates a potentiality for further development of ultrasound
      (US)-enhanced cancer gene therapy.

PMID- 12208342
TI  - Oxidative stress hypothesis of aging.

PMID- 12208341
TI  - Effects of underwater sound exposure on neurological function and brain
      histology.
AB  - To evaluate the safety of sonar exposure from a neurological perspective, the
      vulnerability of the central nervous system to underwater exposure with high
      intensity, low-frequency sound (HI-LFS) was experimentally examined.
      Physiological, behavioral and histological parameters were measured in
      anesthetized, ventilated rats exposed to brief (5 min), underwater HI-LFS.
      Exposure to 180 dB sound pressure level (SPL) re 1 microPa at 150 Hz (n = 9) did
      not alter acute cardiovascular physiology (arterial blood pH, pO(2), pCO(2),
      heart rate, or mean arterial blood pressure) from that found in controls (n =
      11). Rats exposed to either 180 dB SPL re 1 microPa at 150 Hz (n = 12) or 194 dB
      SPL re 1 microPa at 250 Hz (n = 12) exhibited normal cognitive function at 8 and
      9 days after sound exposure. Evaluation of neurological motor function revealed a
      minor deficit 7 days after 180 dB SPL/150 Hz exposure that resolved by 14 days,
      and no deficits after 194 dB SPL/250 Hz exposure. No overt histological damage
      was detected in any group. These data suggest that underwater HI-LFS exposure may
      cause transient, mild motor dysfunction.

PMID- 12208343
TI  - Mechanisms of aging: an appraisal of the oxidative stress hypothesis.
AB  - The main purpose of this article is to provide a critical overview of the
      currently available evidence bearing on the validity of the oxidative stress
      hypothesis of aging, which postulates that senescence-associated attenuations in
      physiological functions are caused by molecular oxidative damage. Several lines
      of correlative evidence support the predictions of the hypothesis, e.g.,
      macromolecular oxidative damage increases with age and tends to be associated
      with life expectancy of organisms. Nevertheless, a direct link between oxidative
      stress and aging has not as yet been established. Single gene mutations have been
      reported to extend the life spans of lower organisms, such as nematodes and
      insects; however, such prolongations of chronological clock time survival are
      usually associated with decreases in the rate of metabolism and reproductive
      output without affecting the metabolic potential, i.e., the total amount of
      energy consumed during life. Studies on genetic manipulations of the aging
      process have often been conducted on relatively short-lived strains that are
      physiologically weak, whereby life-span extensions can not be unambiguously
      assigned to a slowing effect on the rate of aging. It is concluded that although
      there is considerable evidence implicating oxidative stress in the aging process,
      additional evidence is needed to clearly define the nature of the involvement.

PMID- 12208344
TI  - Metabolism and aging in the nematode Caenorhabditis elegans.
AB  - Research into the causes of aging has greatly increased in recent years. Much of
      this interest is due to the discovery of genes in a variety of model organisms
      that appear to modulate aging. Studies of long-lived mutants can potentially
      provide valuable insights into the fundamental mechanisms of aging. While there
      are many advantages to the use of model organisms to study aging it is also
      important to consider the limitations of these systems, particularly because
      ectothermic (poikilothermic) organisms can survive a far greater metabolic
      depression than humans. As such, the consideration of only chronological
      longevity when assaying for long-lived mutants provides a limited perspective on
      the mechanisms by which longevity is increased. Additional physiological
      processes, such as metabolic rate, must also be assayed to provide true insight
      into the aging process. This is especially true in the nematode Caenorhabditis
      elegans, which has the natural ability to enter into a metabolically reduced
      state in which it can survive many times longer than its normal lifetime. The
      extended longevity of at least some long-lived C. elegans mutants may be due to a
      reduction in metabolic rate, rather than an alteration of a metabolically
      independent genetic mechanism specific for aging.

PMID- 12208345
TI  - Importance of individuality in oxidative stress and aging.
AB  - Tight linkage between aging and oxidative stress is indicated by the observations
      that reactive oxygen species generated under various conditions of oxidative
      stress are able to oxidize nucleic acids, proteins, and lipids and that aging is
      associated with the accumulation of oxidized forms of cellular constituents, and
      also by the fact that there is an inverse relationship between the maximum life
      span of organisms and the age-related accumulation of oxidative damage.
      Nevertheless, validity of the oxidative stress hypothesis of aging is questioned
      by (i) the failure to establish a causal relationship between aging and oxidative
      damage and (ii) lack of a consistent correlation between the accumulation of
      oxidative damage and aging. The present discussion is focused on the complexity
      of the aging process and suggests that discrepancies between various studies in
      this area are likely due to the fact that aging is not a single process and that
      the lack of consistent experimental results is partly explained by individual
      variations. Even so, there is overwhelming support for a dominant role of
      oxidative stress in the aging of some individuals.

PMID- 12208346
TI  - A neutral theory predicts multigenic aging and increased concentrations of
      deleterious mutations on the mitochondrial and Y chromosomes.
AB  - Population genetic forces have molded the constitution of the human genome over
      evolutionary time, and some of the most important parameters are the initial
      frequency of the allele, p, the effective population size, Ne, and the selection
      coefficient, s. There is considerable agreement among evolutionary gerontologists
      that the amplitude of -s is small for alleles that are Deleterious In Late Life
      (DILL), and thus DILL traits are effectively neutral and should be fixed in the
      human population in relationship to Ne and p. Even higher rates of fixation of
      deleterious mutations are predicted to occur in the two nonrecombinant genomes in
      humans, i.e., the Y chromosome and the mitochondrial genome, as a consequence of
      their lower Ne than autosomes, and the predicted higher rate of fixation of
      deleterious alleles on the Y may explain the reduced average life span of males
      vs. females. The high probability of fixation of neutral and mildly deleterious
      mutations in the mitochondrial genome explains in part its fast rate of
      evolution, the high observed frequency of mitochondrial disease in relationship
      to this genome's small size, and may be the underlying reason for the transfer of
      mitochondrial genes over evolutionary time to the nucleus. The predicted higher
      concentration of deleterious mutations on the mitochondrial genome could have
      some leverage to cause more dysfunction than that predicted by mitochondrial gene
      number alone, because of the essential role of mitochondrial gene function in
      multisubunit complexes, the coupling of mitochondrial functions, the observation
      that some mtDNA sequences facilitate somatic mutation, and the likelihood of
      deleterious mutations either increasing the production of or the sensitivity to
      mitochondrial ROS.

PMID- 12208347
TI  - Lipofuscin: mechanisms of age-related accumulation and influence on cell
      function.
AB  - The accumulation of lipofuscin within postmitotic cells is a recognized hallmark
      of aging occurring with a rate inversely related to longevity. Lipofuscin is an
      intralysosomal, polymeric substance, primarily composed of cross-linked protein
      residues, formed due to iron-catalyzed oxidative processes. Because it is
      undegradable and cannot be removed via exocytosis, lipofuscin accumulation in
      postmitotic cells is inevitable, whereas proliferative cells efficiently dilute
      it during division. The rate of lipofuscin formation can be experimentally
      manipulated. In cell culture models, oxidative stress (e.g., exposure to 40%
      ambient oxygen or low molecular weight iron) promotes lipofuscin accumulation,
      whereas growth at 8% oxygen and treatment with antioxidants or iron-chelators
      diminish it. Lipofuscin is a fluorochrome and may sensitize lysosomes to visible
      light, a process potentially important for the pathogenesis of age-related
      macular degeneration. Lipofuscin-associated iron sensitizes lysosomes to
      oxidative stress, jeopardizing lysosomal stability and causing apoptosis due to
      release of lysosomal contents. Lipofuscin accumulation may also diminish
      autophagocytotic capacity by acting as a sink for newly produced lysosomal
      enzymes and, therefore, interfere with recycling of cellular components.
      Lipofuscin, thus, may be much more directly related to cellular degeneration at
      old age than was hitherto believed.

PMID- 12208348
TI  - Lipid peroxidation in aging brain and Alzheimer's disease.
AB  - Lipid peroxidation is one of the major outcomes of free radical-mediated injury
      that directly damages membranes and generates a number of secondary products,
      both from fission and endocyclization of oxygenated fatty acids that possess
      neurotoxic activity. Numerous studies have demonstrated increased lipid
      peroxidation in brain of patients with Alzheimer's disease (AD) compared with age
      matched controls. These data include quantification of fission and endocyclized
      products such as 4-hydroxy-2-nonenal, acrolein, isoprostanes, and neuroprostanes.
      Immunohistochemical and biochemical studies have localized the majority of lipid
      peroxidation products to neurons. A few studies have consistently demonstrated
      increased cerebrospinal fluid (CSF) levels of isoprostanes in AD patients early
      in the course of their dementia, and one study has suggested that CSF
      isoprostanes may improve the laboratory diagnostic accuracy for AD. Similar
      analyses of control individuals over a wide range of ages indicate that brain
      lipid peroxidation is not a significant feature of usual aging. Quantification of
      isoprostanes in plasma and urine of AD patients has yielded inconsistent results.
      These results indicate that brain lipid peroxidation is a potential therapeutic
      target in probable AD patients, and that CSF isoprostanes may aid in the
      assessment of antioxidant experimental therapeutics and the laboratory diagnosis
      of AD.

PMID- 12208349
TI  - Effects of coenzyme Q(10) administration on its tissue concentrations,
      mitochondrial oxidant generation, and oxidative stress in the rat.
AB  - Coenzyme Q (CoQ(10)) is a component of the mitochondrial electron transport chain
      and also a constituent of various cellular membranes. It acts as an important in
      vivo antioxidant, but is also a primary source of O(2)(-*)/H(2)O(2) generation in
      cells. CoQ has been widely advocated to be a beneficial dietary adjuvant.
      However, it remains controversial whether oral administration of CoQ can
      significantly enhance its tissue levels and/or can modulate the level of
      oxidative stress in vivo. The objective of this study was to determine the effect
      of dietary CoQ supplementation on its content in various tissues and their
      mitochondria, and the resultant effect on the in vivo level of oxidative stress.
      Rats were administered CoQ(10) (150 mg/kg/d) in their diets for 4 and 13 weeks;
      thereafter, the amounts of CoQ(10) and CoQ(9) were determined by HPLC in the
      plasma, homogenates of the liver, kidney, heart, skeletal muscle, brain, and
      mitochondria of these tissues. Administration of CoQ(10) increased plasma and
      mitochondria levels of CoQ(10) as well as its predominant homologue CoQ(9).
      Generally, the magnitude of the increases was greater after 13 weeks than 4
      weeks. The level of antioxidative defense enzymes in liver and skeletal muscle
      homogenates and the rate of hydrogen peroxide generation in heart, brain, and
      skeletal muscle mitochondria were not affected by CoQ supplementation. However, a
      reductive shift in plasma aminothiol status and a decrease in skeletal muscle
      mitochondrial protein carbonyls were apparent after 13 weeks of supplementation.
      Thus, CoQ supplementation resulted in an elevation of CoQ homologues in tissues
      and their mitochondria, a selective decrease in protein oxidative damage, and an
      increase in antioxidative potential in the rat.

PMID- 12208350
TI  - The role of heme oxygenase-related carbon monoxide and ventricular fibrillation
      in ischemic/reperfused hearts.
AB  - Reperfusion-induced ventricular fibrillation (VF) and heme oxygenase (HO)-related
      carbon monoxide (CO) production in isolated ischemic/reperfused rat hearts were
      studied by gas chromatography. Hearts were subjected to 30 min ischemia followed
      by 2 h reperfusion, and the expression of HO-1 mRNA (about 4-fold) was observed
      in ischemic/reperfused-nonfibrillated hearts. In fibrillated hearts, the
      reduction (about 75%) in HO-1 mRNA expression was detected. These changes in HO-1
      mRNA expression were reflected in tissue CO production. Thus, in the absence of
      VF, CO production was increased about 3.5-fold, while in the presence of VF, CO
      production was under the detectable level in comparison with the control group.
      Our results suggest that the stimulation of HO-1 mRNA expression may lead to the
      prevention of reperfusion VF via an increase in endogenous CO production. To
      prove this, hearts were treated with 1 microM of N-tert-butyl-alpha-phenylnitrone
      (PBN) as an inducer of HO-1. PBN treatment resulted in about 20 times increase in
      HO-1 mRNA expression, and even a higher production rate in endogenous CO. HO
      protein level and enzyme activity followed the same pattern, as it was observed
      in HO-1 mRNA expression, in fibrillated and nonfibrillated myocardium. Five mM/l
      of zinc-protoporphyrin IX (ZnPPIX) significantly blocked HO enzyme activity and
      increased the incidence of VF, therefore the application of ZnPPIX led to a
      significant reduction in HO-1 mRNA and protein expression. Our data provide
      direct evidence of an inverse relationship between the development of reperfusion
      induced VF and endogenous CO production. Thus, interventions that are able to
      increase tissue CO content may prevent the development of reperfusion-induced VF.

PMID- 12208351
TI  - iNOS enhances rat intestinal apoptosis after ischemia-reperfusion.
AB  - The aim of this study was to demonstrate (i) the role of iNOS (inducible nitric
      oxide synthase) on apoptosis in the rat intestinal mucosa after ischemia
      reperfusion, and (ii) the effect of iNOS on the release of cytochrome c from
      mitochondria. The superior mesenteric artery was occluded for 60 min and was
      followed by a 60 min reperfusion. Rats were pretreated with an intraperitoneal
      injection of the following iNOS inhibitors: N-nitro-L-arginine methyl ester,
      aminoguanidine, and (1S,5S,6R,7R)-7- chloro-3-imino-5-methyl-2-azabicyclo [4. 1.
      0] heptane hydrochloride (ONO-1714). Apoptosis was evaluated and NO(X) in the
      portal vein was assayed. The amount of iNOS, caspase-3, and cytochrome c were
      determined by a Western blot analysis. Intestinal mucosal epithelial
      mitochondrial dehydrogenase activity was assessed using 3-(4,5-dimethylthiazol-2
      yl)-2,5-diphenyltetrazoilium bromide. Ischemia-reperfusion increased intestinal
      mucosal apoptosis, NO(X) production in the portal vein, the amount of iNOS
      protein, and the release of cytochrome c, but not caspase-3. Inhibitors of iNOS
      significantly attenuated the induction of apoptosis, increased NO(X) production,
      and release of cytochrome c. Mitochondrial dysfunction was induced by ischemia
      reperfusion, which was ameliorated by iNOS inhibitors. Our results indicate that
      iNOS is related to increased mucosal apoptosis in the rat small intestine after
      ischemia-reperfusion, which is partly explained by the release of cytochrome c
      from mitochondria to cytosols following mitochondrial dysfunction.

PMID- 12208352
TI  - Homocysteine decreases endothelin-1 expression by interfering with the AP-1
      signaling pathway.
AB  - The increased cardiovascular risk associated with hyperhomocysteinemia has been
      linked to homocysteine-induced endothelial cell (EC) dysfunction. Endothelin-1 is
      a vasoactive peptide, synthesized mainly by vascular ECs. We have previously
      shown that homocysteine decreases endothelin-1 biosynthesis. Here we addressed
      the molecular mechanism of endothelin-1 regulation by homocysteine. Experiments
      with the transcription inhibitor actinomycin D indicated that the decrease in
      preproendothelin-1 mRNA content in homocysteine-treated cells did not result from
      transcript destabilization. Transient transfection assays demonstrated that
      homocysteine downregulated endothelin-1 at the transcriptional level by
      decreasing preproendothelin-1 promoter activity. Mutation of the activator
      protein-1 (AP-1) site of the promoter eliminated the repression induced by
      homocysteine. Western blot analysis showed that the homocysteine-induced decrease
      in promoter activity was not associated with reduced expression of the AP-1
      components c-Fos and c-Jun. The inhibitory action of homocysteine on
      preproendothelin-1 mRNA expression was not prevented by cycloheximide.
      Electrophoretic mobility shift assays demonstrated that homocysteine reduced the
      binding activity of ECs nuclear extracts to an AP-1 consensus site. These results
      indicate that homocysteine downregulates endothelin-1 synthesis by inhibiting AP
      1 activity, and that the AP-1 signaling pathway may be of major importance in
      homocysteine-induced endothelial dysfunction.

PMID- 12208353
TI  - Role of oxygen and nitrogen species in experimental uveitis: anti-inflammatory
      activity of the synthetic antioxidant ebselen.
AB  - This study was aimed at examining the role of oxygen and nitrogen reactive
      species in a model of experimental uveitis upon intravitreal injection of
      bacterial endotoxin to albino New Zealand rabbits. The inflammatory response was
      evaluated in terms of: (i) the integrity of the blood aqueous barrier (protein
      and cell content in samples of aqueous humor), (ii) histopathological changes of
      the eyes, (iii) clinical evaluation (with a score index based on clinical
      symptoms), and (iv) the concentration of malondialdehyde (MDA), in aqueous humor,
      as a marker of oxidative stress. Betamethasone was used as reference treatment,
      superoxide dismutase as quencher of superoxide anion, L-N(G)-nitro-L-arginine
      methyl-esther (L-NAME) and chlorpromazine as nitric oxide synthase inhibitors,
      and ebselen, a glutathione peroxidase mimic, as peroxynitrite reductant. All the
      substances were injected subconjunctivally to the rabbits immediately after the
      intravitreal endotoxin injection. Ebselen was the only treatment able to decrease
      MDA concentration to control values, exerting an effect similar to that elicited
      by L-NAME on the rest of the parameters tested. The data presented render ebselen
      a notable choice for the treatment of uveitis, with implications for clinical
      trials.

PMID- 12208354
TI  - Increased nitric oxide-dependent nitrosylation of 4,5-diaminofluorescein by
      oxidants: implications for the measurement of intracellular nitric oxide.
AB  - 4,5 diaminofluorescein (DAF-2) is increasingly utilized as a fluorescent detector
      for nitric oxide (*NO) in cells and tissues. In oxygenated solutions, reactive
      nitrogen species derived from (*) NO autoxidation nitrosate DAF-2 to yield the
      highly fluorescent DAF-2 triazole. In the present study, we investigated the
      nitrosation of DAF-2 at a neutral pH by absorption and fluorescence spectroscopy
      using NONOates as chemical sources of (*) NO. We found that both chemically
      synthesized peroxynitrite and horseradish peroxidase in the presence of hydrogen
      peroxide (H(2)O(2)) oxidized DAF-2 to a relatively stable nonfluorescent
      intermediate (t(1/2) approximately 90 s). Oxidation of DAF-2 prior to the
      addition of the z.rad;NO donor DEA/NO resulted in an increase in fluorescence
      that was approximately 7-fold higher than treatment with DEA/NO alone. The
      increase in DAF-2 triazole formation upon oxidation of DAF-2 was confirmed by
      high performance liquid chromatography. Peroxynitrite generated in situ from the
      equimolar production of (*) NO and superoxide (O(2)(*-)) also increased the
      yields of DAF-2 triazole formation, which was completely inhibited when O(2)(*-)
      was in excess of (*) NO. We propose that DAF-2 is oxidized to a free radical
      intermediate that directly reacts with (*) NO, thereby bypassing the requirement
      for (*)NO autoxidation for the formation of DAF-2 triazole. Our findings indicate
      that DAF-2 fluorometric assays are quantitatively difficult to interpret in cells
      and in solution when oxidants and (*) NO are co-generated.

PMID- 12208355
TI  - Pathways of dopamine oxidation mediated by nitric oxide.
AB  - This study was aimed at establishing the interaction between dopamine and nitric
      oxide and elucidating the mechanistic aspects inherent in this interaction. At
      high (*) NO concentrations (microM range), dopamine underwent nitrosation with
      subsequent nitration. Nitrosation is proposed to occur via a nucleophilic attack
      to N(2)O(3) by dopamine. At low (*) NO concentrations (microM range),
      dopaminochrome was formed. EPR spin stabilization studies showed the occurrence
      of two o-semiquinone intermediates during dopaminochrome formation. Heats of
      formation obtained by AM1 semiempirical calculations supported the formation of
      the two o-semiquinone species. Hydroxyl radicals were detected by spin trapping
      EPR, and experiments performed with superoxide dismutase and catalase suggested
      that peroxynitrite was the source of HO(*). A mechanism is presented that
      considers the several factors influencing these reactions.

PMID- 12208356
TI  - DNA damage and apoptosis in hydrogen peroxide-exposed Jurkat cells: bolus
      addition versus continuous generation of H(2)O(2).
AB  - Aspects of the molecular mechanism(s) of hydrogen peroxide-induced DNA damage and
      cell death were studied in the present investigation. Jurkat T-cells in culture
      were exposed either to low rates of continuously generated H(2)O(2) by the action
      of glucose oxidase or to a bolus addition of the same agent. In the first case,
      steady state conditions were prevailing, while in the latter, H(2)O(2) was
      removed by the cellular defense systems following first order kinetics. By using
      single-cell gel electrophoresis (also called comet assay), an initial increase in
      the formation of DNA single-strand breaks was observed in cells exposed to a
      bolus of 150 microM H(2)O(2). As the H(2)O(2) was exhausted, a gradual decrease
      in DNA damage was apparent, indicating the existence of an effective repair of
      single-strand breaks. Addition of 10 ng glucose oxidase in 100 microl growth
      medium (containing 1.5 x 10(5) cells) generated 2.0 +/- 0.2 microM H(2)O(2) per
      min. This treatment induced an increase in the level of single-strand breaks
      reaching the upper limit of detection by the methodology used and continued to be
      high for the following 6 h. However, when a variety of markers for apoptotic cell
      death (DNA cell content, DNA laddering, activation of caspases, PARP cleavage)
      were examined, only bolus additions of H(2)O(2) were able to induce apoptosis,
      while the continuous presence of this agent inhibited the execution of the
      apoptotic process no matter whether the inducer was H(2)O(2) itself or an anti
      Fas antibody. These observations stress that, apart from the apparent genotoxic
      and proapoptotic effects of H(2)O(2), it can also exert antiapoptotic actions
      when present, even at low concentrations, during the execution of apoptosis.

PMID- 12208357
TI  - Metabolism of carcinogenic urethane to nitric oxide is involved in oxidative DNA
      damage.
AB  - Carcinogenic urethane (ethyl carbamate) forms DNA adduct via epoxide, whereas
      carcinogenic methyl carbamate can not. To clarify a mechanism independent of DNA
      adduct formation, we examined DNA damage induced by N-hydroxyurethane, a urethane
      metabolite, using 32P-5'-end-labeled DNA fragments. N-hydroxyurethane induced
      Cu(II)-mediated DNA damage especially at thymine and cytosine residues. DNA
      damage was inhibited by both catalase and bathocuproine, suggesting a role for
      H(2)O(2) and Cu(I) in DNA damage. Free (*) OH scavengers did not inhibit the DNA
      damage, although methional did inhibit it. These results suggest that reactive
      species, such as the Cu(I)-hydroperoxo complex, cause DNA damage. Formation of 8
      oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG) was increased by N-hydroxyurethane in
      the presence of Cu(II). When treated with esterase, N-hydroxyurethane induced 8
      oxodG formation to a similar extent as that induced by hydroxylamine. Enhancement
      of DNA cleavages by endonuclease IV suggests that hydroxylamine induced
      depurination. Furthermore, hydroxylamine induced a significant increase in 8
      oxodG formation in HL-60 cells but not in its H(2)O(2)-resistant clone HP 100
      cells. o-Phenanthroline significantly inhibited the 8-oxodG formation in HL-60
      cells, confirming the involvement of metal ions in the 8-oxodG formation by
      hydroxylamine. Electron spin resonance spectroscopy, utilizing Fe[N
      (dithiocarboxy)sarcosine](3), demonstrated that nitric oxide (NO) was generated
      from hydroxylamine and esterase-treated N-hydroxyurethane. It is concluded that
      urethane may induce carcinogenesis through oxidation and, to a lesser extent,
      depurination of DNA by its metabolites.

PMID- 12208358
TI  - Analysis of mitochondrial free radical generation in animal models of neuronal
      disease.
AB  - Mitochondria, the power plant of all eukaryotic cells, produce cellular energy in
      the form of ATP via electron transport and oxidative phosphorylation. However,
      the mitochondria leak electrons that can act as major sources of oxidative
      stress, and their dysfunction, have been proposed as causative events underlying
      neurodegeneration in stroke and neurodegenerative diseases. We examined whether
      MitoTracker Red CM-H(2)XRos, a rosamine derivative used to detect mitochondrial
      free radicals in vitro, would be applied to analyze the mitochondrial free
      radicals in various models of neurological diseases in vivo. The injections of
      MitoTracker Red CM-H(2)XRos revealed generation of mitochondrial free radicals
      primarily in vulnerable neurons following focal cerebral ischemia as well as
      administration of Fe(2+) or 3-nitropropionic acid. MitoTracker Red CM-H(2)XRos
      was retained after fixation, compatible with immunocytochemistry or nuclear
      staining, and can be applied to study roles of mitochondrial free radicals in the
      process of neurodegeneration in vivo.

PMID- 12208361
TI  - The nitration of proteins in platelets: significance in platelet function.
AB  - Exogenous peroxynitrite has been shown to inhibit or activate platelets according
      to the concentration added and, at the same time, nitrate platelet proteins.
      Here, recent evidence is discussed which indicates that nitration of proteins may
      also occur during normal platelet activation by collagen, by mechanical
      stimulation during isolation and by exposure to low levels of hydrogen peroxide.
      Furthermore, this nitration appears to be transient. The implications of these
      findings are discussed in terms of platelet biology and cell signaling processes.

PMID- 12208362
TI  - Peroxynitrite signaling: receptor tyrosine kinases and activation of stress
      responsive pathways.
AB  - Peroxynitrite, generated for example in inflammatory processes, is capable of
      nitrating and oxidizing biomolecules, implying a considerable impact on the
      integrity of cellular structures. Cells respond to stressful conditions by the
      activation of signaling pathways, including receptor tyrosine kinase-dependent
      pathways such as mitogen-activated protein kinases and the phosphoinositide-3
      kinase/Akt pathway. Peroxynitrite affects signaling pathways by nitration as well
      as by oxidation: while nitration of tyrosine residues by peroxynitrite modulates
      signaling processes relying on tyrosine phosphorylation and dephosphorylation,
      oxidation of phosphotyrosine phosphatases may lead to an alteration in the
      tyrosine phosphorylation/dephosphorylation balance. The flavanol (-)-epicatechin
      is a potent inhibitor of tyrosine nitration and may be employed as a tool to
      distinguish signaling effects due to tyrosine nitration from those that are due
      to oxidation reactions.

PMID- 12208363
TI  - Peroxynitrite activates kinases of the src family and upregulates tyrosine
      phosphorylation signaling.
AB  - The hypothesis that peroxynitrite may act as a signaling molecule able to
      upregulate protein tyrosine phosphorylation is discussed. This article focuses on
      the mechanisms for activating kinases of the src family, an important class of
      nonreceptor tyrosine kinases implicated in the regulation of cell communication,
      proliferation, migration, differentiation, and survival. Recent in vitro findings
      show that in erythrocytes, synaptosomes, and cerebellar primary culture cells
      peroxynitrite is able to inhibit phosphatases and to activate different members
      of the src kinase family through different mechanisms involving cysteine
      dependent and -independent processes. The ability of nitrotyrosine-containing
      peptides with SH2 binding affinity to activate src kinases is also discussed.

PMID- 12208364
TI  - Mitochondria: regulators of signal transduction by reactive oxygen and nitrogen
      species.
AB  - The functional role of mitochondria in cell physiology has previously centered
      around metabolism, with oxidative phosphorylation playing a pivotal role.
      Recently, however, this perspective has changed significantly with the
      realization that mitochondria are active participants in signal transduction
      pathways, not simply the passive recipients of injunctions from the rest of the
      cell. In this review the emerging role of the mitochondrion in cell signaling is
      discussed in the context of cytochrome c release, hydrogen peroxide formation
      from the respiratory chain, and the nitric oxide-cytochrome c oxidase signaling
      pathway.

PMID- 12208365
TI  - Signal transduction by protein tyrosine nitration: competition or cooperation
      with tyrosine phosphorylation-dependent signaling events?
AB  - This review article is an attempt to stimulate a discussion on the significance
      of protein tyrosine nitration to cellular signaling and its relationships with
      protein tyrosine phosphorylation. Initially, it provides basic information on
      growth factor and oxidants as modulators/mediators of tyrosine phosphorylation
      dependent signal transduction pathways. The effects of exogenous and endogenous
      tyrosine nitration on such pathways were examined by reviewing published and
      unpublished observations. From an initial perspective that tyrosine nitration was
      a toxic manifestation of nitric oxide, the concept evolved to a protein
      modification that could also function in cellular signaling events, possibly
      cooperating with tyrosine phosphorylation.

PMID- 12208366
TI  - Structure and function of xanthine oxidoreductase: where are we now?
AB  - Xanthine oxidoreductase (XOR) is a complex molybdoflavoenzyme, present in milk
      and many other tissues, which has been studied for over 100 years. While it is
      generally recognized as a key enzyme in purine catabolism, its structural
      complexity and specialized tissue distribution suggest other functions that have
      never been fully identified. The publication, just over 20 years ago, of a
      hypothesis implicating XOR in ischemia-reperfusion injury focused research
      attention on the enzyme and its ability to generate reactive oxygen species
      (ROS). Since that time a great deal more information has been obtained concerning
      the tissue distribution, structure, and enzymology of XOR, particularly the human
      enzyme. XOR is subject to both pre- and post-translational control by a range of
      mechanisms in response to hormones, cytokines, and oxygen tension. Of special
      interest has been the finding that XOR can catalyze the reduction of nitrates and
      nitrites to nitric oxide (NO), acting as a source of both NO and peroxynitrite.
      The concept of a widely distributed and highly regulated enzyme capable of
      generating both ROS and NO is intriguing in both physiological and pathological
      contexts. The details of these recent findings, their pathophysiological
      implications, and the requirements for future research are addressed in this
      review.

PMID- 12208367
TI  - Rosmarinic acid, a major polyphenolic component of Perilla frutescens, reduces
      lipopolysaccharide (LPS)-induced liver injury in D-galactosamine (D-GalN)
      sensitized mice.
AB  - The protective activity of rosmarinic acid from Perilla frutescens on liver
      injury induced by LPS in D-GalN-sensitized mice was examined. We also
      investigated the effects of antitumor necrosis factor-alpha antibody (anti-TNF),
      superoxide dismutase (SOD), and aminoguanidine (AG) on this model in order to
      elucidate the mechanism of rosmarinic acid protection. Perilla extract (PE) and
      rosmarinic acid (RA) treatments significantly reduced the elevation of plasma
      asparatate aminotransferase levels, as well as anti-TNF and SOD treatment,
      compared with controls, but this reduction was not seen in the AG group. These
      results were confirmed by histological examination using hematoxylin-eosin and in
      situ terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL)
      staining. Increases in tumor necrosis factor-alpha (TNF-alpha) mRNA expression in
      liver and in plasma TNF-alpha levels, which were observed in control mice, were
      not significantly reduced by PE or RA. PE and RA treatments also did not
      significantly diminish iNOS mRNA expression or plasma nitrate/nitrite levels.
      Nitrotyrosine and N(epsilon)-(hexanonyl)lysine (HEL) production, the residue of
      oxidative stress, was observed in livers from controls, but not in those mice
      pretreated with PE or RA. These results suggest that the liver protection of RA
      is due to the scavenging or reducing activities-superoxide or peroxynitirite
      rather than to inhibition of TNF-alpha production.

PMID- 12208368
TI  - Synthesis and analysis of conjugates of the major vitamin E metabolite, alpha
      CEHC.
AB  - Glucuronide and sulphate conjugates of 2,5,7,8-tetramethyl-2-(2'-carboxyethyl)-6
      hydroxychroman (alpha-CEHC), the major metabolite of alpha-tocopherol (vitamin
      E), have been synthesized and used for the first direct analysis of conjugated
      urinary vitamin E metabolites. The metabolites of vitamin E (alpha-tocopherol)
      could be useful as markers of the function(s) of vitamin E in vivo. A number of
      methods have been described for the analysis of urinary vitamin E metabolites but
      these have relied on either acid or enzymatic deconjugation of the metabolites
      prior to analysis by high performance liquid chromatography or gas
      chromatography/mass spectrometry. These methods have provided useful information
      about the amount and types of metabolites excreted in the urine but suffer from a
      number of disadvantages. Deconjugation has been shown to produce artifacts as a
      result of the conversion of alpha-CEHC to alpha-tocopheronolactone and the
      efficiency of deconjugation is also difficult to assess. Methods that allow the
      direct measurement of the conjugated metabolites would overcome these problems
      and would also substantially reduce the preparation and analysis time. Here we
      describe the use of conjugated standards to characterize alpha-CEHC conjugates in
      human urine by tandem mass spectrometry (MS-MS). The future use of MS-MS to
      measure urinary vitamin E metabolites is also discussed.

PMID- 12208369
TI  - In vivo production of hydroxyl radical by Enterococcus faecalis colonizing the
      intestinal tract using aromatic hydroxylation.
AB  - Enterococcus faecalis is an intestinal commensal that produces extracellular
      superoxide (O(2)(*-)) through autoxidation of membrane-associated
      demethylmenaquinone. To assess free radical production by E. faecalis in vivo,
      intestinal tracts of rats were colonized using wild-type E. faecalis or a mutant
      strain with attenuated O(2)(*-) production. Ex vivo electron paramagnetic
      resonance spin trapping study of colonic contents (mean +/- SD) showed 1.4 +/-
      1.5 and 0.094 +/- 0.24 microM 5,5-dimethyl-1-pyrroline-N-oxide-hydroxyl radical
      adduct/gm stool for rats colonized with wild-type and mutant strains,
      respectively (p = .002). In vivo hydroxyl radical production was further assayed
      by aromatic hydroxylation using phenyl N-tert-butylnitrone (PBN) and D
      phenylalanine. Hydroxylated PBN and D-phenylalanine products were recovered from
      stool (microM/gm colonic contents/10(9) colony forming units) and urine
      (microM/h/ml), respectively, and quantified using electrochemical detection.
      Hydroxylated (OH) PBNs and isomeric tyrosines (hydroxylated phenylalanine) were
      significantly increased (mean +/- SD) for rats colonized with wild-type E.
      faecalis (2-OH PBN, 63 +/- 58; 3-OH PBN, 63 +/- 84; ortho-tyrosine, 31 +/- 27;
      meta-tyrosine, 17 +/- 14) compared to the mutant strain (2-OH PBN, 2.5 +/- 7.3 (p
      < .001); 3-OH PBN, 3.9 +/- 12.3 (p = .01); ortho-tyrosine, 1.9 +/- 6.0 (p <
      .001); meta-tyrosine, 1.5 +/- 3.4 (p = .03)). Similar differences were observed
      following in vitro incubations of these bacteria with aromatic targets. These
      results confirm in vivo production of hydroxyl radical by E. faecalis colonizing
      the intestine, and indicate this bacterium may be a potent source of oxidative
      stress on the intestinal epithelium.

PMID- 12208370
TI  - Ingress and reactive chemistry of nitroxyl-derived species within human cells.
AB  - The mechanisms that control the biological signaling and toxicological properties
      of the nitrogen oxide species nitroxyl (HNO) are largely unknown. The ingress and
      intracellular reactivity of nitroxyl-derived species were examined using Angeli's
      salt (AS), which decomposes initially to HNO and nitrite at physiologic pH.
      Exposure of 4,5-diaminofluorescein (DAF) to AS resulted in fluorescent product
      formation only in the presence of molecular oxygen. Kinetic analysis and the lack
      of signal from a nitric oxide (NO)-sensitive electrode suggested that these
      processes did not involve conversion of HNO to NO. On an equimolar basis, bolus
      peroxynitrite (ONOO(-)) exposure generated only 15% of fluorescent product
      formation observed from AS decomposition. Moreover, infusion of synthetic ONOO(-)
      at a rate comparable to AS decomposition resulted in only 4% of the signal.
      Quenching of AS-mediated product formation within intact human MCF-7 breast
      carcinoma cells containing DAF by addition of urate to buffer suggested
      involvement of an oxidized intermediate formed from reaction between HNO and
      oxygen. Conversely, intact cells competitively sequestered the HNO-derived
      species from reaction with DAF in solution. These data show this intermediate to
      be a long-lived diffusible species. Relative product yield from intracellular DAF
      was decreased 5- to 8-fold when cells were lysed immediately prior to AS
      addition, consistent with the partitioning of HNO and/or derived species into the
      cellular membrane, thereby shielding these reactive intermediates from either
      hydrolysis or cytoplasmic scavenger pools. These findings establish that oxygen
      derived species of nitroxyl can readily penetrate and engage the intracellular
      milieu of cells and suggest this process to be independent of NO and ONOO(-)
      intermediacy. The substantial facilitation of oxygen-dependent nitroxyl chemistry
      by intact lipid bilayers supports a focusing role for the membrane in modulation
      of cellular constituents proteins by this unique species.

PMID- 12208371
TI  - Attenuating effects of heat shock against TGF-beta1-induced apoptosis in cultured
      rat hepatocytes.
AB  - Heat shock proteins (HSPs) induction confers protection against diverse forms of
      cellular injury. However, the mechanism by which HSPs exert cytoprotective
      effects remains unclear. Treatment of rat hepatocyte with transforming growth
      factor-beta1 (TGF-beta1) induces growth arrest followed by extensive cell death
      by apoptosis. In this study, the effects of preexposure to heat on TGF-beta1
      induced apoptosis of cultured hepatocytes were examined. Treatment of hepatocytes
      for 24 h with TGF-beta1 resulted in significant apoptotic cell death, as
      demonstrated by DNA fragmentation, caspase activation, and hypodiploid DNA peak.
      Moreover, TGF-beta1-induced cell death was accompanied by an enhanced generation
      of reactive oxygen species and a loss of the mitochondrial membrane potential.
      These effects were attenuated when the hepatocytes were subjected to 43 degrees C
      for 20 min prior to the cytokine stimulation. The enhancement in HSP70 expression
      at mRNA and protein levels induced by heat preexposure was accompanied by an
      increase in mRNA levels of intracellular antioxidant enzymes. Heat treatment also
      prevented TGF-beta1-induced activation of nuclear factor kappa B (NF-kappaB) by
      preventing the degradation of the inhibitory protein kappa Balpha (IkappaBalpha).
      In conclusion, these data indicate that in the mechanism by which a mild heat
      pretreatment increases the resistance of hepatocytes to TGF-beta1-induced
      apoptotic cell death, the upregulation of catalase expression and a decrease in
      ROS generation are involved.

PMID- 12208372
TI  - Eosinophil peroxidase produces hypobromous acid in the airways of stable
      asthmatics.
AB  - Eosinophil peroxidase and myeloperoxidase use hydrogen peroxide to produce
      hypobromous acid and hypochlorous acid. These powerful oxidants may damage the
      lungs if they are produced as part of the inflammatory response in asthma. The
      aim of this study was to determine if peroxidases generate hypohalous acids in
      the airways of individuals with stable asthma, and if they affect lung function.
      Sputum was induced from patients with mild to moderate asthma and from healthy
      controls. Eosinophil peroxidase, myeloperoxidase, chlorinated and brominated
      tyrosyl residues, and protein carbonyls were measured in sputum supernatants.
      Eosinophil peroxidase protein was significantly elevated in asthmatic subjects
      whereas myeloperoxidase protein was not. There was significantly more 3
      bromotyrosine (Br-Tyr) in proteins from the sputum of asthmatics compared to
      controls (0.79 vs. 0.23 mmol Br-Tyr/mol Tyr; medians p < .0001). Levels of 3
      chlorotyrosine (0.23 vs. 0.14 mmol Cl-Tyr/mol Tyr; medians p = .11) and protein
      carbonyls (0.347 vs. 0.339 nmol/mg protein; medians p = .56) were not
      significantly increased in asthmatics. Levels of 3-bromotyrosine were strongly
      correlated with eosinophil peroxidase protein (r = 0.79, p < .0001). There were
      no significant correlations between the markers of oxidative stress and lung
      function. We conclude that eosinophil peroxidase produces substantial amounts of
      hypobromous acid in the airways of stable asthmatics. Although this highly
      reactive oxidant is a strong candidate for exacerbating inflammatory tissue
      damage in the lung, its role in asthma remains uncertain.

PMID- 12208373
TI  - A small molecular weight catalytic metalloporphyrin antioxidant with superoxide
      dismutase (SOD) mimetic properties protects lungs from radiation-induced injury.
AB  - Radiation therapy (RT) is an important therapeutic modality in the treatment of
      thoracic tumors. The maximum doses to these tumors are often limited by the
      radiation tolerance of lung tissues. Lung injury from ionizing radiation is
      believed to be a consequence of oxidative stress and a cascade of cytokine
      activity. Superoxide dismutase (SOD) is a key enzyme in cellular defenses against
      oxidative damage. The objective of this study was to determine whether the SOD
      mimetic AEOL 10113 [manganese (III) mesotetrakis (N-ethylpyridinium-2-yl)
      porphyrin (MnTE-2-PyP(5+))] increases the tolerance of lung to ionizing
      radiation. AEOL 10113 was able to significantly reduce the severity of RT-induced
      lung injury. This was strongly supported with histopathology results and
      measurements of collagen deposition (hydroxyproline content). There was a
      significant reduction in the plasma level of the profibrogenic cytokine
      transforming growth factor-beta (TGF-beta) in the group of rats receiving RT +
      AEOL 10113. In conclusion, the novel SOD mimetic, AEOL 10113, demonstrates a
      significant protective effect from radiation-induced lung injury.

PMID- 12208374
TI  - Involvement of reactive oxygen species in arsenite-induced downregulation of
      phospholipid hydroperoxide glutathione peroxidase in human epidermoid carcinoma
      A431 cells.
AB  - Phospholipid hydroperoxide glutathione peroxidase (PHGPx) is unique in the
      substrate specificity among the glutathione peroxidase family because it can
      interact with lipophilic substrates, including the peroxidized phospholipids and
      cholesterol, and reduce these hydroperoxide to hydroxide compounds. However, what
      kinds of ligand can regulate the PHGPx expression is still unknown. In the
      present study, we found that sodium arsenite induced downregulation of mRNA,
      protein expression, and enzyme activity of PHGPx in time- and dose-dependent
      manners. At the same time, it upregulated mRNA and protein expression of
      p21(WAF1/CIP1). With the aid of agarose gel electrophoresis, and propidium iodide
      and annexin-V staining, we found that treatment of 30 microM sodium arsenite for
      24 h induced apoptosis in human epidermoid carcinoma A431 cells and EA.hy926
      cells. An increase of intracellular peroxide levels was measured by flow
      cytometry using 2',7'-dichlorofluorescin diacetate (DCFH-DA) after treatment of
      arsenite. Overexpression of PHGPx prevented arsenite-induced increase of
      intracellular peroxide levels, downregulation of PHGPx, upregulation of
      p21(WAF1/CIP1), and apoptosis in A431 cells. N-Acetyl-L-cysteine also
      significantly prevented arsenite-induced effects in A431 cells. Therefore, we
      concluded that reactive oxygen species were involved in arsenite-induced
      downregulation of PHGPx, upregulation of p21(WAF1/CIP1), and apoptosis in A431
      cells.

PMID- 12208375
TI  - Outcomes of medically treated patients with aortic intramural hematoma.
AB  - PURPOSE: Aortic intramural hematoma has been considered a precursor of aortic
      dissection, and the same treatment strategy, usually involving surgery, has been
      applied to both conditions. However, the outcomes of patients with aortic
      intramural hematoma who are treated medically, including the remodeling process
      that occurs after an acute event, are not known. SUBJECT AND METHODS: A total of
      124 patients with acute aortic intramural hematoma (41 in the proximal aorta and
      83 in the distal aorta) was enrolled from five institutions in South Korea.
      Patients received medical treatment without surgery. A follow-up imaging study
      was performed in 105 patients. RESULTS: Pericardial (59% [n = 24] vs. 11% [n =
      9], P <0.004) and pleural effusions (63% [n = 26] vs. 45% [n = 37], P = 0.05)
      were more common in patients with the proximal type than in those with the distal
      type. In-hospital mortality was somewhat higher with proximal hematomas (7% [n =
      3 deaths] vs. 1% [n = 1 death], P = 0.11). A follow-up imaging study in 36
      patients with proximal hematomas confirmed resorption of the hematoma in 24
      patients (67%) and development of aortic dissection in 9 (25%). Resorption was
      confirmed in 54 (78%) of the 69 patients with distal hematomas who underwent
      follow-up imaging; localized aortic dissection developed in 11 (16%) of these
      patients. The 3-year survival rate was 78% in the proximal type and 87% in the
      distal type (P = 0.10). CONCLUSION: Patients with aortic intramural hematoma had
      a high rate of resorption with medical treatment regardless of the affected site.
      Further investigation is necessary to determine the optimal treatment strategy
      and timing of surgical intervention, especially for patients with proximal
      hematomas.

PMID- 12208376
TI  - Effects of antirheumatic therapy on serum lipid levels in patients with
      rheumatoid arthritis: a prospective study.
AB  - BACKGROUND: Patients with newly diagnosed rheumatoid arthritis have adverse serum
      lipid profiles. We sought to determine the effects of treating rheumatoid
      arthritis with antirheumatic drugs on these abnormal lipid levels. SUBJECTS AND
      METHODS: We studied 42 patients with newly diagnosed rheumatoid arthritis who had
      not been treated with corticosteroids or disease-modifying antirheumatic drugs.
      We measured serum lipid profiles at baseline and 1 year later, and determined
      whether there were differences in the changes in lipid levels between patients
      who met the American College of Rheumatology criteria for a 20% improvement in
      rheumatoid arthritis and those who did not. RESULTS: Of the 42 patients, 27 (64%)
      met the criteria for a 20% improvement in rheumatoid arthritis during the 12
      month study. In these patients, mean high-density lipoprotein (HDL) cholesterol
      levels increased by 21% (P <0.001), apolipoprotein A-I levels increased by 23% (P
      <0.001), and the ratio of low-density lipoprotein (LDL) cholesterol to HDL
      cholesterol level decreased by 13% (P = 0.10). There were significant between
      group differences (responders-nonresponders) in the mean 12-month changes in HDL
      cholesterol levels (8.0 mg/dL; 95% confidence interval [CI]: 3 to 13 mg/dL; P =
      0.002), apolipoprotein A-I levels (21 mg/dL; 95% CI: 8 to 33 mg/dL; P = 0.003),
      and the LDL cholesterol to HDL cholesterol ratio (-0.6; 95% CI: -0.1 to -1.0; P =
      0.03), but not in LDL cholesterol, apolipoprotein B-100, or lipoprotein(a)
      levels. CONCLUSION: Active rheumatoid arthritis is associated with an adverse
      lipid profile that improves substantially following effective treatment of
      rheumatoid arthritis. This improvement may reduce the risk of cardiovascular
      disease.

PMID- 12208377
TI  - Prevalence of monoclonal gammopathy in patients presenting with acquired
      angioedema type 2.
AB  - PURPOSE: Acquired angioedema type 1 is characterized by a C1 inhibitor deficiency
      in patients with lymphoproliferative disorders, whereas acquired angioedema type
      2 is characterized by anti-C1 inhibitor antibodies, and has not been thought to
      be associated with lymphoproliferative disease. We studied the clinical features,
      complement profiles, and associated diseases in 19 new patients with diagnosed
      acquired angioedema type 2. SUBJECTS AND METHODS: Plasma concentrations and
      functional activity of complement components were measured by conventional
      techniques. Functional C1 inhibitor activity was assessed by a chromogenic assay.
      Autoantibodies to C1 inhibitor were detected using an enzyme-linked immunosorbent
      assay. RESULTS: The 11 men and 8 women (median age, 60 years) presented with
      recurrent attacks of angioedema. All patients had detectable anti-C1 inhibitor
      antibodies in serum. A monoclonal gammopathy was detected in 12 patients (63%) at
      the time of diagnosis, 11 of whom had an immunoglobulin peak of the same heavy-
      and light-chain isotypes as the acquired anti-C1 inhibitor antibody. Three of
      these 12 patients developed a malignant lymphoproliferative disease. CONCLUSION:
      As with type 1 disease, a large proportion of patients with acquired angioedema
      type 2 have a lymphoproliferative disorder.

PMID- 12208378
TI  - Racial and sex differences in refusal of coronary angiography.
AB  - PURPOSE: To determine the effect of patient refusal on racial and sex differences
      in the use of coronary angiography and in outcomes among elderly patients with
      acute myocardial infarction. SUBJECTS AND METHODS: We included Medicare
      beneficiary patients admitted to hospitals performing coronary angiography from
      February 1994 through July 1995. In-hospital use and refusal of coronary
      angiography were determined, and adjusted for patient, hospital, and physician
      characteristics. RESULTS: Of 124,691 patients, 53,671 (43%) underwent angiography
      during hospitalization and 2881 (2.3%) refused. Patients refusing angiography
      were more likely to be female (odds ratio [OR] = 1.37; 95% confidence interval
      [CI]: 1.23 to 1.53), black (OR = 1.26 vs. whites; 95% CI: 1.02 to 1.56), and
      older (OR = 2.25 per 10-year increase; 95% CI: 2.05 to 2.43) than patients who
      underwent angiography. Angiography use was lower in blacks (OR = 0.78; 95% CI:
      0.72 to 0.83) than in whites, and lower in women (OR = 0.83; 95% CI: 0.80 to
      0.86) than in men. Increased refusal explained 6% (95% CI: -3% to 15%) of the
      difference in angiography use between whites and blacks, and 16% (95% CI: 10% to
      22%) of the difference between men and women. After adjustment for patient
      characteristics, refusal of angiography was not associated with worse survival at
      1 year (OR = 0.99; 95% CI: 0.82 to 1.20). CONCLUSION: Among Medicare
      beneficiaries, elderly female and black patients are more likely to refuse
      angiography than are male and white patients. However, patient refusal is
      uncommon and accounts for only a small fraction of the racial and sex differences
      in use of angiography after myocardial infarction.

PMID- 12208379
TI  - Dissociation of hospitalization and mortality trends for myocardial infarction in
      the United States from 1988 to 1997.
AB  - PURPOSE: Although age-adjusted mortality from myocardial infarction in the United
      States has declined during the past few decades, changes in the incidence of
      myocardial infarction are less certain. To address this issue, we evaluated
      trends in hospitalization for, and in-hospital mortality from, myocardial
      infarction from 1988 to 1997. METHODS: Hospitalization rates were determined by
      age and sex using data from the National Hospital Discharge Survey and the
      Current Population Survey. Comorbid conditions, complications, use of cardiac
      procedures, and in-hospital mortality were measured. In-hospital mortality was
      estimated after adjusting for associated risk factors, complications, use of
      invasive diagnostic and therapeutic procedures, and length of stay. RESULTS: Age
      adjusted rates of hospitalization for myocardial infarction were 525 per 100,000
      in 1988 and 482 per 100,000 in 1997, with a mean annual decline of 0.8% (P =
      0.32). Mortality declined from 58 per 100,000 in 1988 to 40 per 100,000 in 1997,
      a mean annual decline of 4.2% (P = 0.01). During these 10 years, although the
      median hospital stay for myocardial infarction decreased from 8 to 5 days, the
      intensity of hospital care increased, including use of angiography from 20% to
      31% (P = 0.04) and revascularization from 16% to 31% (P = 0.004). Age-adjusted in
      hospital mortality decreased by nearly half, from 7.6% in 1988 to 3.9% in 1997 (P
      = 0.006). CONCLUSION: During the past decade, the decline in mortality from
      myocardial infarction in the United States has not been accompanied by a decline
      in hospitalization rate. At the same time, there has been a marked increased in
      the use of cardiac revascularization.

PMID- 12208380
TI  - Preliminary data on the potential usefulness of B-type natriuretic peptide levels
      in predicting outcome after hospital discharge in patients with heart failure.
AB  - PURPOSE: Among patients admitted for treatment of heart failure, we aimed to
      evaluate the value of B-type natriuretic peptide levels in predicting subsequent
      death or hospital readmission. SUBJECTS AND METHODS: We observed and followed 50
      consecutive patients admitted with decompensated heart failure. B-type
      natriuretic peptide levels were measured using an immunofluorometric assay at
      admission and at discharge. We followed patients for 6 months and ascertained
      readmissions for cardiovascular causes and death. RESULTS: Forty-three patients
      were discharged. There were 20 events during follow-up (15 readmissions and 5
      deaths). Mean (+/- SD) B-type natriuretic peptide levels decreased during the
      initial hospitalization, from 619 +/- 491 pg/mL to 328 +/- 314 pg/mL (P <0.001)
      among patients who were event free during follow-up, whereas declines were less
      marked among patients with hospital readmission or death (from 779 +/- 608 pg/mL
      to 643 +/- 465 pg/mL, P = 0.08). Among the 7 patients with in-hospital increases
      in B-type natriuretic peptide level, 6 had events, compared with 14 of the 36
      patients whose levels declined (P = 0.04). An increase in B-type natriuretic
      peptide levels during hospital stay was associated with an increased event rate
      (hazard ratio [HR] = 3.3; 95% confidence interval [CI]: 1.3 to 8.8). Patients
      whose B-type natriuretic peptide level at discharge was above the median (321
      pg/mL) had a somewhat higher rate of dying or being readmitted (HR = 2.3; 95% CI:
      0.9 to 5.8). CONCLUSION: These preliminary results in a small number of patients
      suggest that changes in B-type natriuretic peptide levels, as well as
      predischarge levels, are related to hospital readmission and death within 6
      months.

PMID- 12208381
TI  - Diagnosis and management of vertebral fractures in elderly adults.
AB  - We reviewed the epidemiology, diagnosis, and treatment of vertebral fractures due
      to osteoporosis in the elderly. Vertebral fractures are underdiagnosed despite
      their high prevalence in both men and women. Clinical consequences of vertebral
      fractures include increased risk of future vertebral and hip fracture, acute and
      chronic back pain, decreased quality of life, and increased mortality. Patients
      with vertebral fractures have functional impairment and increased mortality
      similar to those with hip fractures. Asymptomatic fractures identified on
      radiograph also affect quality of life and mortality. A vertebral fracture is a
      clinical marker for a subsequent fracture and should trigger assessment and
      diagnosis of osteoporosis. The care of patients with vertebral fractures includes
      pain management, rehabilitation, and prevention of further fractures. There is
      evidence from randomized controlled trials that pharmacologic therapy can reduce
      the risk of future fractures by 40% to 50%. Vertebroplasty may be effective in
      the control of pain and in obtaining stability of the spine.

PMID- 12208382
TI  - Adverse effects of medications and trade-offs between length of life and quality
      of life in human immunodeficiency virus infection.

PMID- 12208383
TI  - Severe and persistent hypoglycemia due to gatifloxacin interaction with oral
      hypoglycemic agents.

PMID- 12208384
TI  - Factors associated with mortality among elderly patients with hypothermia.

PMID- 12208385
TI  - D-dimer levels in patients with suspected acute cerebral venous thrombosis.

PMID- 12208386
TI  - Cases from the Osler Medical Service at Johns Hopkins University. Herpetic
      keratitis.

PMID- 12208387
TI  - Intramural hematoma of the aorta: should we let down our guard?

PMID- 12208388
TI  - Improving joint disease in patients with rheumatoid arthritis: is this enough to
      treat the accompanying dyslipidemias?

PMID- 12208389
TI  - The "neurotic" edema: the parent disease and its offspring.

PMID- 12208390
TI  - Sildenafil relieves priapism in patients with sickle cell disease.

PMID- 12208391
TI  - Glaucoma in primary amyloidosis: a fortuitous or causative association?

PMID- 12208392
TI  - Acute hepatitis induced by parenteral amiodarone.

PMID- 12208393
TI  - Growth hormone therapy for non-islet cell tumor hypoglycemia.

PMID- 12208394
TI  - Paratyphoid hepatitis: an emerging clinical entity.

PMID- 12208395
TI  - Nephrotic syndrome presenting as dural sinus thrombosis.

PMID- 12208396
TI  - The absence of rhabdomyolysis-induced renal failure following the World Trade
      Center collapse.

PMID- 12208397
TI  - Visceral involvement due to Leishmania mexicana in a patient with acquired
      immunodeficiency syndrome.

PMID- 12208398
TI  - Successful medical management of emphysematous pyelonephritis.

PMID- 12208399
TI  - Crossing the quality chasm: the role of postgraduate training.

PMID- 12208400
TI  - Comparison of real-time coherent contrast imaging to dipyridamole thallium-201
      single-photon emission computed tomography for assessment of myocardial perfusion
      and left ventricular wall motion.
AB  - Real-time coherent contrast imaging (CCI) echocardiography has the ability to
      evaluate wall motion and myocardial perfusion simultaneously, but its clinical
      applicability in the diagnosis of coronary artery disease (CAD) remains to be
      determined. This study examines the level of agreement between real-time CCI
      echocardiography and thallium-201 single-photon emission computed tomography
      (SPECT) following stress vasodilation. Forty-two patients with known or suspected
      CAD underwent real-time CCI using octafluoropropane-filled microspheres infusion
      before and after dipyridamole and thallium-201 injections. The apical 4- and 2
      chamber views were each divided into 6 segments to assess wall motion and
      perfusion. Real-time CCI and SPECT were interpreted independently. Thirty-eight
      patients successfully completed tests, and 4 had suboptimal contrast images. Each
      vascular territory was classified as normal or abnormal by CCI perfusion, wall
      motion, and SPECT at baseline and at stress. Of the 114 territories (3 in each of
      the 38 patients), 3 (3.5%) were not analyzed; however, all territories
      corresponding to the left anterior descending artery were suitable for analysis.
      Concordance between CCI echocardiography and thallium-201 SPECT perfusion for
      left anterior descending, left circumflex, and right coronary artery territories
      were 91%, 86%, and 69%, respectively; between CCI perfusion and wall motion, the
      correlations were 93%, 93%, and 91%, respectively. When CCI perfusion and wall
      motion analysis were combined, their concordance to thallium-201 SPECT uptake
      improved to 94%, 89%, and 79%, respectively. In conclusion, real-time CCI
      echocardiography agrees very closely with thallium-201 SPECT in assessing
      myocardial perfusion following vasodilatory stress. Assessment of myocardial
      perfusion, in addition to segmental wall motion analysis, during stress
      echocardiography may be a significant contribution to the noninvasive evaluation
      of patients with ischemic heart disease.

PMID- 12208401
TI  - Reason for discrepancies in identifying myocardial viability by thallium-201
      redistribution, magnetic resonance imaging, and dobutamine echocardiography.
AB  - Dobutamine echocardiography (DE), magnetic resonance imaging (MRI), and thallium
      redistribution (TS) are used to assess cardiac viability. However, these
      modalities sometimes yield contradictory results. Our aim was to establish the
      degrees of agreement among DE, MRI, and TS in identifying myocardial viability
      and to analyze the minimum critical mass of live (viable) cells required for each
      test to identify viability. A prospective study was done in which DE, MRI, and TS
      were consecutively performed in 10 ischemic patients scheduled for heart
      transplantation. The explanted heart was analyzed to quantify the amount of live
      cells per segment. The pathologic data were compared with the test results to
      analyze the minimum mass of viable cells required by each technique to identify
      viability. Mean age was 58 +/- 8 years (8 men). The mean ejection fraction was
      0.27 +/- 0.04. Seven patients had severe cardiac failure (New York Heart
      Association functional class IV) and 6 patients had refractory angina. A total of
      150 cardiac segments were analyzed. Among the 150 segments, 107 (71.3%) showed
      some degree of myocardial necrosis. Mean total area, mean fatty area, and mean
      necrotic area per segment were 2.53 +/- 0.7, 0.13 +/- 0.2, and 0.55+/-0.5 cm(2),
      respectively. As expected, a higher amount of necrotic tissue was found in
      nonviable segments. From the 150 segments, DE identified 90 as viable and 60 as
      nonviable. These data were similar to that of MRI (98 viable and 52 nonviable). A
      higher proportion of viable segments was found by TS (117 viable vs 33
      nonviable). The concordance between DE and TS was only moderate (kappa 0.49). The
      agreement between MRI and TS also showed moderate concordance (kappa 0.56). The
      highest agreement was found between DE and MRI (kappa 0.73). Thus, discrepancies
      in assessing viability by DE, MRI, and TS may be due to differences in the
      minimum critical mass of live myocytes required by each technique to diagnose
      viability. Thallium requires a lesser amount of live tissue than DE or MRI to
      detect viability; also, its maximum diagnostic efficiency is obtained with lesser
      amounts of live tissue on each segment. These considerations should be taken into
      account when these diagnostic tests are used for the detection of viability
      before revascularization procedures.

PMID- 12208402
TI  - Randomized comparison of success and adverse event rates and cost effectiveness
      of one long versus two short stents for treatment of long coronary narrowings.
AB  - Long stents of high flexibility and low profile have become widely available.
      Treatment of long coronary lesions by 1 long stent may require less
      interventional efforts and reduce the rate of restenosis due to a lack of
      overlapping stent segments. This study sought to evaluate the use of 1 long stent
      compared with 2 short stents for treatment of long coronary lesions. One-hundred
      twenty-four patients with a coronary lesion 20 to 40 mm in length, in a vessel
      2.5 to 4.0 mm in diameter, were randomly assigned to treatment with 1 long stent
      (GFX II stents or S670 of 24, 30, or 40 mm lengths; n = 62) or 2 stents (GFX II
      or S670 stents, n = 62) of equal length. Procedural success, interventional
      costs, as well as long-term clinical and angiographic outcomes were evaluated.
      Lesion characteristics were similar for the 2 treatment groups. Stent placement
      was possible as assigned by randomization in 61 of 62 cases (98%) in the 1-long
      stent group and 100% of cases in the 2-short-stents group. There was crossover to
      successful short-stent placement in 1 case. The in-hospital success rate was 97%
      for the 1-long-stent group and 98% for the 2-short-stents group. Acute
      angiographic results were similar for both groups after intervention. The
      angiographic restenosis rate at 6 months was 38.5% in the 1-long-stent group and
      37.5% in the 2-short-stents group (p = 0.919). Intervention time was less, and
      the need for a contrast agent had a tendency to be lower in the long-stent group.
      Procedural costs were significantly less in the long-stent group. In conclusion,
      1 long stent can be used with identical procedural success and adverse event
      rates as 2 short stents in long, atherosclerotic coronary lesions. The restenosis
      rate is not reduced by the use of 1 long stent compared with 2 stents. However,
      long stent placement is highly cost effective.

PMID- 12208403
TI  - Effect of preinfarction angina pectoris on ST-segment resolution after primary
      coronary angioplasty for acute myocardial infarction.
AB  - The presence of preinfarction angina has been shown to exert a favorable effect
      on left ventricular function after acute myocardial infarction (AMI). Whether or
      not preinfarction angina is beneficial for myocardial tissue reperfusion,
      however, remains to be determined. We sought to evaluate the influence of
      preinfarction angina on resolution of ST-segment elevation, which could be
      affected by microcirculatory damage after recanalization therapy. We studied 96
      patients with a first AMI in whom Thrombolysis In Myocardial Infarction (TIMI)-3
      flow in the infarct-related artery was established by primary angioplasty.
      Percent reduction in the sum of ST elevation from baseline to 1 hour after
      angioplasty (percent delta summation operator ST) was examined. Poor ST
      resolution, defined as percent delta summation operator ST <50%, was observed in
      25 patients, who had a worse clinical outcome, larger infarct size, and poorer
      left ventricular function. On multivariate analysis, the absence of preinfarction
      angina, as well as anterior wall infarction, were major independent predictors of
      poor ST resolution, whereas age, sex, coronary risk factors, ischemic time,
      Killip class on admission, multivessel disease, initial TIMI flow grade, and
      extent of collaterals were not significant. Patients with preinfarction angina
      had a greater degree of ST-segment resolution than those without angina (71 +/-
      21% vs 49 +/- 43%, p = 0.02). Additional ST elevation after reperfusion was noted
      exclusively in patients without preinfarction angina (p = 0.02). Preinfarction
      angina is associated with a greater degree of ST-segment resolution in patients
      with TIMI-3 flow after primary angioplasty, suggesting a protective effect of
      preinfarction angina against microcirculatory damage after reperfusion.

PMID- 12208404
TI  - Effectiveness of rheolytic coronary thrombectomy with the AngioJet catheter.
AB  - Thrombus-filled lesions are associated with a higher rate of acute complications
      and long-term restenosis following conventional coronary or saphenous vein graft
      (SVG) intervention. To evaluate the clinical effectiveness of rheolytic
      thrombectomy in a nonselected population in the glycoprotein IIb/IIIa blockade
      era, we reviewed clinical, angiographic, and procedural data on 119 patients who
      underwent 126 consecutive coronary AngioJet procedures (29% in SVGs, and 71% in
      native coronary arteries) from July 1998 to August 2000. Glycoprotein IIb/IIIa
      blockers were used in 88%. Most vessels (68% of SVGs, 74% of native coronary
      arteries) were occluded initially. Complete or substantial removal of filling
      defects was achieved in 76% of SVGs and 66% of native coronary cases. The
      AngioJet rheolytic thrombectomy device led to significant improvement in lumen
      diameter and Thrombolysis In Myocardial Infarction (TIMI) flow, with reduction in
      the thrombotic lesion length (p <0.05). Angiographic success (<30% residual
      stenosis, TIMI-3) was attained in 73% of SVGs and 87% of native coronary
      procedures. Distal embolization occurred in 13 cases, and was less likely to
      occur in patients treated with abciximab (0%) compared with patients treated with
      other glycoprotein IIb/IIIa blockers or heparin alone (17%, p = 0.02). A
      favorable response to the AngioJet (odds ratio 3.9) and freedom from embolization
      (odds ratio 14.6) were associated with a higher procedural success rate. In
      hospital and long-term clinical outcomes were favorable. Thus, rheolytic
      thrombectomy resulted in significant reduction of the thrombus burden in most
      patients, restored TIMI-3 flow, and led to favorable short- and long-term
      outcomes.

PMID- 12208405
TI  - Comparison of enoxaparin versus unfractionated heparin in patients with unstable
      angina pectoris/non-ST-segment elevation acute myocardial infarction having
      subsequent percutaneous coronary intervention.
AB  - Patients with unstable angina or non-ST-segment elevation myocardial infarction
      (MI) may undergo invasive revascularization procedures shortly after admission to
      hospital or after a brief period of stabilization. In the Thrombolysis In
      Myocardial Infarction (TIMI) 11B trial and Efficacy and Safety of Subcutaneous
      Enoxaparin in Non-Q-Wave Coronary Events (ESSENCE) trial 1,326 patients underwent
      percutaneous coronary intervention (PCI). A total of 924 patients underwent PCI
      during the initial hospitalization period, and of these, 445 patients did so
      while receiving treatment with unfractionated heparin (UFH) or the low-molecular
      weight heparin, enoxaparin. This analysis compared efficacy and clinical events
      in the enoxaparin and UFH groups in patients who: (1) underwent PCI while on
      treatment versus those who did not, and (2) underwent PCI in hospital. We also
      compared those who did not undergo PCI. Treatment with enoxaparin (1 mg/kg given
      as twice daily subcutaneous injections) was beneficial and well tolerated in
      patients with unstable angina and non-ST-segment elevation MI who underwent PCI.
      Compared with UFH, enoxaparin significantly reduced the likelihood of clinical
      events (death and nonfatal MI after PCI) in patients who underwent PCI after 1
      year (p = 0.003 for in-hospital PCI; p = 0.005 for on-treatment PCI), with a
      trend toward a reduced event rate at 43 days. In addition, patients treated with
      enoxaparin who did not undergo PCI also showed a reduction in the risk of death,
      nonfatal MI, and urgent revascularization when compared with those treated with
      UFH (significant at 43 days, with a trend persisting at 1 year). Study
      limitations were that PCI was nonrandomized, the analysis was post hoc, and the
      sample size was relatively small. Nevertheless, in the absence of large clinical
      trials, this study suggests that treatment with enoxaparin was well tolerated,
      and exhibited a similar risk of major hemorrhage to UFH in patients who underwent
      PCI.

PMID- 12208406
TI  - Relation of QT interval dispersion to the number of different cardiac
      abnormalities in diabetes mellitus.
AB  - Three studies have clearly shown that a prolonged QT dispersion (QTD) is the best
      predictor of cardiac death in patients with type 2 diabetes mellitus (DM). This
      was originally believed to be because QTD identified electrical inhomogeneity,
      but recent data suggests that this is unlikely. The alternative possibility is
      that QTD is a convenient identifier of hidden but lethal cardiac abnormalities.
      We explored whether the latter possibility is true by examining exactly what
      spectrum of cardiac abnormalities, if any, are over-represented in diabetics with
      a prolonged QTD. Two hundred nineteen patients with type 2 DM who had been first
      diagnosed with DM 3 to 6 years previously underwent intensive cardiac
      examinations. Patients with prolonged QTD had a significantly increased incidence
      of myocardial ischemia and left ventricular (LV) hypertrophy, and to a lesser
      extent, autonomic dysfunction. The main independent determinant of a prolonged
      QTD was ischemia, as seen on both ambulatory ST-segment monitoring (p <0.001) and
      Duke score on treadmill testing (p <0.001). It was also observed that QTD
      increased progressively as the number of different cardiac abnormalities
      increased (p <0.001). These studies suggest that QTD is a useful, general
      prescreening test to select diabetics for more detailed cardiac examinations
      (especially for ischemia and LV hypertrophy), and that if cardiac examinations
      were targeted by way of QTD screening, then a high incidence of hidden but
      treatable cardiac abnormalities could be found.

PMID- 12208407
TI  - Comparison between isoproterenol and nitroglycerin sensitized head-upright tilt
      in patients with unexplained syncope and negative or positive passive head-up
      tilt response.
AB  - It is unknown if the head-upright tilt test in patients who receive isoproterenol
      and nitroglycerin can identify different populations with vasovagal syncope. The
      aim of this study was to compare the positive or negative responses to passive
      tilt between isoproterenol- and nitroglycerin-sensitized upright tilt. Ninety-six
      patients referred for unexplained recurrent syncope underwent passive tilt (45
      minutes at 70 degrees angle), which was then systematically followed, within the
      same session and in a random order, by a 20-minute tilt at a 70 degrees angle
      after administration of nitroglycerin (NTG-tilt) and 10-minute tilt at a 70
      degrees angle with a continuous infusion of isoproterenol (ISO-tilt). NTG-tilt
      led to significantly more positive responses than passive tilt or ISO-tilt (55%
      vs 34% vs 42%, respectively). In the subgroup of patients with a positive
      response during passive tilt, the percentage of positive responses with NTG-tilt
      was significantly higher than with ISO-tilt (94% vs 67%). The agreement between
      NTG-tilt and ISO-tilt was very weak (Kappa coefficient 0.06). In the subgroup of
      patients with a negative response during passive tilt, the percentage of positive
      responses between NTG-tilt and ISO-tilt was similar (35% vs 29%). The agreement
      between NTG-tilt and ISO-tilt was good (Kappa coefficient 0.34). NTG-tilt led to
      a higher number of positive responses than ISO-tilt, especially when passive tilt
      outcome was positive. These 2 pharmacologic agents may identify 2 different
      subpopulations of patients because of their specific pharmacologic actions.

PMID- 12208408
TI  - Comparison of amiodarone versus ibutilide for the prevention of immediate
      recurrences of atrial fibrillation during pulmonary vein isolation.
AB  - During segmental ostial ablation for pulmonary vein isolation, pulmonary vein
      potentials are easily identified during sinus rhythm or left atrial pacing.
      Therefore, maintenance of atrial fibrillation (AF) during the procedure is
      desirable. However, cardioversion is occasionally followed by an immediate
      recurrence of AF. This study compared the efficacy of ibutilide and amiodarone in
      preventing immediate recurrences of AF in patients who underwent pulmonary vein
      isolation. The subjects of this study were 25 patients (mean age 56 +/- 10 years)
      who underwent pulmonary vein isolation for AF who had an immediate recurrence of
      AF within 60 seconds after 2 transthoracic cardioversions. The patients were
      randomized to receive an infusion of either 300 mg of amiodarone over 10 minutes
      or 1 mg of ibutilide over 5 minutes. Cardioversion was repeated 15 minutes after
      the drug infusion. If immediate recurrences of AF occurred 2 more times, the
      alternative study drug was administered, and cardioversion was repeated.
      Immediate recurrences of AF were suppressed by amiodarone in 8 of 10 patients
      (80%), and by ibutilide in 9 of 15 patients (60%, p = 0.4). After crossover,
      immediate recurrence of AF was suppressed in 2 of 6 patients (33%) by amiodarone,
      and in 1 of 2 patients (50%) by ibutilide (p = 0.6). Ibutilide and amiodarone,
      when used alone or in combination, prevented immediate recurrences of AF in 20 of
      25 patients (80%). There were no adverse drug effects. Ibutilide and amiodarone
      were equally effective in suppressing immediate recurrences of AF. Overall,
      immediate recurrences of AF can be prevented by amiodarone and/or ibutilide in
      80% of patients.

PMID- 12208409
TI  - Comparison of the effects of omapatrilat and lisinopril on circulating
      neurohormones and cytokines in patients with chronic heart failure.
AB  - Angiotensin-converting enzyme (ACE) inhibitors exert their effects by modulating
      the neurohumoral milieu. Vasopeptidase inhibitors (VPI) are ACE and neutral
      endopeptidase inhibitors and may increase natriuretic peptides, bradykinin, and
      perhaps endothelin-1 in patients with congestive heart failure. Patients (n =
      107) with ischemic or dilated cardiomyopathy, New York Heart Association
      functional class II to III, with left ventricular ejection fraction <40%, and on
      ACE inhibitor therapy were randomized to either the VPI omapatrilat 40 mg/day or
      the ACE inhibitor lisinopril 20 mg/day. Trough levels of neurohormones (24 hours
      after dosing) were assessed at baseline, and at 12 and 24 weeks of follow-up. C
      terminal atrial natriuretic peptide (C-ANP) levels decreased with lisinopril (p =
      0.035), but not with omapatrilat. In contrast, N-terminal ANP levels did not
      change, and brain natriuretic peptide (BNP) levels tended to decrease similarly
      in both groups. Endothelin-1 levels increased in both groups, the increase
      reaching statistical significance with omapatrilat (p = 0.008). Levels of the
      proinflammatory cytokine interleukin-6 tended to decrease, and the anti
      inflammatory cytokine interleukin-10 increased in both groups, with statistical
      significance only for interleukin-10 with omapatrilat therapy. Neither agent
      changed catecholamines or angiotensin II. Thus, even at trough levels,
      omapatrilat potentiates C-ANP more than lisinopril. Potentially important effects
      of omapatrilat on endothelin-1 and anti-inflammatory cytokines were identified,
      providing potential explanations for differences in clinical outcome.

PMID- 12208410
TI  - Outcome of idiopathic restrictive cardiomyopathy in children.
AB  - Eighteen children with idiopathic restrictive cardiomyopathy (IRC) were studied
      in an attempt to identify potential predictors of poor outcome. Four patients
      presented with low cardiac output (CO) syndrome. Fourteen remaining patients were
      minimally symptomatic at presentation but developed a low CO syndrome at a mean
      of 2.8 +/- 2.3 years after diagnosis. At the time of development of low CO in the
      18 patients, mean left ventricular end-diastolic pressure was 27 mm Hg, right
      ventricular end-diastolic pressure was 18 mm Hg, cardiac index was 2.5
      L/min/m(2), and pulmonary vascular resistance index (PVRI) was 8.8 U-m(2). Eleven
      of the 18 patients underwent cardiac transplantation. One died perioperatively
      from donor right-sided cardiac failure and 10 survived. Six were not transplanted
      and died, including 3 in whom transplantation was precluded secondary to
      extremely elevated PVRI. One patient is alive with right-sided cardiac failure.
      Ten of our 18 patients had pulmonary hypertension (PVRI >6 U-m(2)) at the time of
      referral for cardiac transplant and/or development of low CO syndrome. In
      comparison, children with dilated cardiomyopathy who were referred for heart
      transplant during the same time period had a PVRI that was significantly lower
      (5.2 U-m(2)). Elevated PVRI was associated with death (p <0.01) and 40% of our
      children with pulmonary hypertension were precluded from receiving an orthotopic
      heart transplant because their pulmonary hypertension was so severe. No risk
      factors for the development of pulmonary hypertension were identified; therefore,
      all children with IRC should undergo serial monitoring of their PVRI, and any
      increase should prompt a transplant evaluation.

PMID- 12208411
TI  - Disturbed right ventricular ejection pattern as a new Doppler echocardiographic
      sign of acute pulmonary embolism.
AB  - Transthoracic echocardiography (TTE) is frequently performed in patients with
      suspected acute pulmonary embolism (APE) to search for right ventricular (RV)
      pressure overload. We prospectively assessed the diagnostic value of a new
      Doppler echocardiographic sign of APE based on the disturbed RV ejection pattern
      ("60/60 sign") and compared its diagnostic performances with that of the presence
      of RV pressure overload, as well as with "McConnell sign" based on RV regional
      wall motion abnormalities. We assessed 100 consecutive patients with clinical
      suspicion of APE, including those with previous cardiorespiratory diseases. After
      TTE, all of the patients underwent reference diagnostic tests for APE. The 60/60
      sign required RV acceleration time of <or=60 ms in presence of tricuspid
      insufficiency pressure gradient <or=60 mm Hg. APE was ultimately confirmed in 67
      of 100 patients. In 17 of 67 patients, 60/60 sign correctly suggested APE,
      whereas 2 false-positive results were noted: in pulmonary fibrosis and in acute
      respiratory distress syndrome following lung resection. McConnell sign was fully
      specific but was noted in only 13 of 67 patients. Sensitivity and specificity
      were 81% and 45% for "RV-pressure overload" signs, 25% and 94% for 60/60 sign,
      and 19% and 100% for McConnell sign. When combined, the 2 latter signs were 94%
      specific and 36% sensitive in diagnosing APE. Thus, RV overload at
      echocardiography is not specific for APE. The 60/60 and McConnell signs are
      insensitive, but are reliable and helpful in bedside diagnosis of APE when direct
      visualization of the pulmonary arteries is impossible. Combining these 2 signs
      may increase the sensitivity without compromising the specificity of
      echocardiographic diagnosis of APE.

PMID- 12208412
TI  - Phase I study of direct administration of a replication deficient adenovirus
      vector containing the vascular endothelial growth factor cDNA (CI-1023) to
      patients with claudication.
AB  - The long-term safety and efficacy of adenoviral delivery of growth factors in
      patients with peripheral arterial disease (PAD) is unknown. CI-1023
      (Ad(GV)VEGF(121.10)) is a replication-deficient adenovirus encoding human
      vascular endothelial growth factor isoform 121. In this phase I trial, we
      investigated the safety and efficacy of CI-1023 in subjects with advanced
      claudication symptoms secondary to infra-inguinal disease. Eighteen subjects >35
      years of age with a median ankle brachial index (ABI) at rest of 0.525
      (interquartile range 0.4) and angiographic disease involving the infra-inguinal
      vessels underwent intramuscular injection of CI-1023 (4 x10(8) to 4 x10(10)
      particle units, n = 15) or placebo (n = 3). Eleven of 15 patients (73%) who
      received CI-1023 and 1 of 3 subjects (33%) who received placebo, completed 1 year
      of follow-up. Edema and rash were the most common early adverse event. One infra
      inguinal bypass procedure occurred in each of the placebo and CI-1023 groups at
      days 29 and 104, respectively. One death (day 160) and 1 malignancy (day 274)
      occurred in the CI-1023 group. Conclusions on efficacy could not be made due to
      the small number of patients. However, there were encouraging trends in ABI at
      rest and peak walking time at follow-up.

PMID- 12208413
TI  - Usefulness of the combined index of systolic and diastolic myocardial performance
      to identify cardiac allograft rejection.
AB  - Systolic and diastolic myocardial performance characteristics are altered during
      allograft rejection. Noninvasive diagnostic markers of allograft rejection have
      thus far not been found to be clinically useful and have not replaced routine
      endomyocardial biopsy as a method to detect rejection. We examined the clinical
      utility of the Index of Myocardial Performance (IMP), or the Tei index, a
      combined index of systolic and diastolic performance (derived as a composite
      ratio of isovolumetric contraction time and isovolumetric relaxation time to the
      ejection time), in evaluating and following cardiac allograft rejection. Twenty
      heart transplant recipients with moderate cellular rejection (International
      Society for Heart and Lung Transplantation [ISHLT] grade 3A) underwent
      echocardiographic assessment to derive the IMP at baseline (rejection free),
      during treatment of rejection, and after recovery from rejection (group I). A
      parallel group of 20 nonrejecters (ISHLT grade 1A) were also similarly examined
      to serve as controls (group II). In group I patients, there was a mean increase
      of IMP by 98% (p <0.0001) during the rejection episode compared with baseline.
      After treatment, IMP decreased to its baseline value. In the control group there
      was no significant change in IMP over time. An IMP increase of >/=20% from
      baseline had 90% sensitivity and 90% specificity in detecting high-grade cardiac
      allograft rejection. The change in IMP in patients with grade 3A cellular
      rejection was independent of both the ejection fraction at baseline and change in
      ejection fraction during the rejection episode. These results indicate that
      changes in IMP, a sensitive marker of early diastolic and systolic performance,
      accurately evaluate the development of, and recovery from, cardiac allograft
      rejection. IMP can provide a clinically useful noninvasive indicator to assess
      the impact of therapy for amelioration of allograft rejection.

PMID- 12208414
TI  - The DVI mode of cardiac pacing: a second coming?

PMID- 12208415
TI  - Reassessment of National Cholesterol Education Program Adult Treatment Panel-III
      guidelines: one year later.

PMID- 12208416
TI  - Effectiveness of tirofiban, eptifibatide, and abciximab in minimizing myocardial
      necrosis during percutaneous coronary intervention (TEAM pilot study).

PMID- 12208417
TI  - Status of glucose metabolism in patients with heart failure secondary to coronary
      artery disease.

PMID- 12208418
TI  - Effects of abciximab pretreatment in patients with acute myocardial infarction
      undergoing primary angioplasty.

PMID- 12208419
TI  - Effect of implementation of folic acid fortification of food on homocysteine
      concentrations in subjects with coronary artery disease.

PMID- 12208420
TI  - Comparison of volumetric intravascular ultrasound analysis of acute results and
      underlying mechanisms from cutting balloon and conventional balloon angioplasty
      for the treatment of coronary in-stent restenotic lesions.

PMID- 12208421
TI  - Frequency and severity of "incidentalomas" encountered during electron beam
      computed tomography for coronary calcium in middle-aged army personnel.

PMID- 12208422
TI  - Association of the G20210A mutation in the factor II gene with systemic embolism
      in nonvalvular atrial fibrillation.

PMID- 12208423
TI  - Impact of an exercise-induced increase in cardiac troponin I in chronic heart
      failure secondary to ischemic or idiopathic dilated cardiomyopathy.

PMID- 12208424
TI  - Association of aortic stenosis with platelet hyperaggregability and impaired
      responsiveness to nitric oxide.

PMID- 12208425
TI  - Correlation of degree of aortic valve stenosis by Doppler echocardiogram to
      quantity of calcium in the valve by electron beam tomography.

PMID- 12208426
TI  - Flow dynamics in the left anterior descending coronary artery in infants with
      idiopathic dilated cardiomyopathy.

PMID- 12208427
TI  - Red blood cell adhesiveness/aggregation, C-reactive protein, fibrinogen, and
      erythrocyte sedimentation rate in healthy adults and in those with
      atherosclerotic risk factors.

PMID- 12208428
TI  - Sex distribution in cardiac myxomas.

PMID- 12208429
TI  - Comparison of the right ventricular Tei index by tissue Doppler imaging to that
      obtained by pulsed Doppler in children without heart disease.

PMID- 12208430
TI  - Simplified echocardiographic criteria for decision making in perimembranous
      ventricular septal defect in childhood.

PMID- 12208432
TI  - Lipoprotein changes during acute coronary syndromes.

PMID- 12208433
TI  - Cardiac testing for noncardiac surgery: past, present, and future.

PMID- 12208434
TI  - Comparison of total intravenous anesthesia and sevoflurane-fentanyl anesthesia
      for outpatient otorhinolaryngeal surgery.
AB  - STUDY OBJECTIVE: To compare the recovery characteristics of two widely used
      anesthetic techniques: remifentanyl-propofol and sevoflurane-fentanyl in a
      standardized ambulatory population. DESIGN: Randomized, single-blinded study.
      SETTING: University-affiliated medical center. PATIENTS: 50 ASA physical status I
      and II patients undergoing elective ambulatory otorhinolaryngeal surgery.
      INTERVENTIONS: Patients were randomized two groups to receive total intravenous
      anesthesia (TIVA group) with remifentanil and propofol or sevoflurane-fentanyl
      (SF group). TIVA patients received induction with propofol 1.5 mg/kg
      intravenously (IV) and remifentanil 0.5 microg/kg IV. The anesthesia was
      continued with a continuous infusion of propofol 100 microg/kg/min and
      remifentanil 0.0625-0.25 microg/kg/min. The SF group received, at induction,
      fentanyl 2 microg/kg followed by propofol 1.5 mg/kg IV. Maintenance was obtained
      with 1 to 1.5 minimum alveolar concentration of sevoflurane and bolus of fentanyl
      1 microg/kg IV as needed. MEASUREMENTS AND MAIN RESULTS: Early recovery times
      (eye opening, response to commands, extubation, orientation, operating room stay
      after surgery, and Aldrete score > or =9) and patient satisfaction were similar
      between the two groups. Postanesthetic discharge scoring system (PADSS) > or = 9
      was significantly shorter for the TIVA group (135.9 +/- 51 vs. 103 +/- 32 min) (p
      < 0.01) but this difference was not associated with a shorter postanesthesia care
      unit (PACU) length of stay. CONCLUSION: Early recovery times are comparable
      between total intravenous anesthesia and sevoflurane-based anesthesia. Even
      though patients in the TIVA group achieved home readiness criteria in a
      significantly shorter time, this technique does not shorten PACU length of stay,
      which depends instead on multiple nonmedical and administrative issues.

PMID- 12208435
TI  - Polypharmacy, age, and scheduled surgery.
AB  - STUDY OBJECTIVE: To test the hypothesis that there is a correlation between the
      age of patients who present for scheduled surgery and the number of drugs taken
      by these patients. DESIGN: Prospective clinical study. SETTING: Outpatient
      admissions. PATIENTS: 150 ASA physical status I, II, and III patients 40 years of
      age or older, scheduled for outpatient surgery. INTERVENTIONS: None.
      MEASUREMENTS: Age, medical history, and prescription and nonprescription
      medications of these patients were recorded. MAIN RESULTS: There was no
      significant difference among number of drugs taken by patients in different age
      groups [40 to 49 years: 3.2 +/- 3.1 (average number of drugs taken, standard
      deviation); 50 to 59 years: 3.6 +/- 3.1; 60 to 69 years: 4.0 +/- 2.9; 70 to 79
      years: 4.4 +/- 2.7; 80+ years: 3.7 +/- 2.2]. CONCLUSIONS: Medical condition,
      which may, in part, be a function of biological age and not chronological age, is
      the primary determinant of the number of medications taken by patients presenting
      to an outpatient clinic for scheduled surgery.

PMID- 12208436
TI  - Head and neck elevation beyond the sniffing position improves laryngeal view in
      cases of difficult direct laryngoscopy.
AB  - STUDY OBJECTIVE: To determine the influence of head and neck elevation beyond the
      "sniffing position" during difficult direct laryngoscopy. DESIGN: Prospective
      case series, with each patient serving as her or his control. SETTING: University
      hospital. PATIENTS: 21 patients scheduled for general anesthesia and endotracheal
      intubation, all of whom presented with a laryngoscopic grade III view (Cormack &
      Lehane) during direct laryngoscopy in the sniffing position. INTERVENTIONS: An
      assistant applied external laryngeal pressure with his left hand and elevated the
      patient's head and neck above the sniffing position with his right hand to
      improve laryngeal view. MEASUREMENTS AND MAIN RESULTS: External laryngeal
      pressure and elevation of head and neck improved the laryngoscopic view in 19 of
      21 patients to grade II (p = 0.001, Wilcoxon signed rank test). Beyond that,
      laryngoscopy with the neck maximally elevated enabled visualization of parts of
      the cords in six patients (30%). CONCLUSIONS: Elevation of the head and neck
      beyond the sniffing position may improve visualization of glottic structures in
      cases of difficult direct laryngoscopy, leading to better intubation performance.

PMID- 12208437
TI  - Comparison of effects of lidocaine hydrochloride, buffered lidocaine,
      diphenhydramine, and normal saline after intradermal injection.
AB  - STUDY OBJECTIVE: To evaluate pain and the spread of analgesia when local
      anesthetics are given as an intradermal injection into the dorsal aspect of the
      hand. DESIGN: Randomized, double-blinded, placebo-controlled study. SETTING:
      University medical center. PATIENTS: 40 consenting adult volunteers.
      INTERVENTIONS: Volunteers were randomly assigned to receive a 0.25-mL injection
      of either lidocaine hydrochloride (1%), buffered lidocaine, diphenhydramine (1%),
      or placebo (0.9% sodium chloride solution) into the dorsal aspect of both hands.
      MEASUREMENTS: The volunteers used a visual analog scale to compare the pain of
      needle insertion and solution injection. Then at 1, 2, 5, 10, 20, and 30 minutes
      after intradermal injection, the extent of the analgesic area was marked on a
      strip of tape placed horizontally across the hand. Then at 32 minutes after
      intradermal injection, the extent of the analgesic area was marked on a strip of
      tape placed vertically across the hand. The volunteers were called each day and
      asked the duration of their numbness or hyperesthesia until their hands were no
      longer numb or sore. MAIN RESULTS: Buffered lidocaine during intradermal
      infiltration was found to be significantly (p < 0.05) less painful than either
      lidocaine hydrochloride or diphenhydramine and equivalent to placebo.
      Diphenhydramine and lidocaine hydrochloride during intradermal infiltration
      induced significantly (p < 0.05) more pain than buffered lidocaine or placebo.
      Lidocaine hydrochloride displayed a significantly (p < 0.05) larger diameter of
      analgesia than placebo by 1 minute after the injection, buffered lidocaine by 2
      minutes after injection, and diphenhydramine by 5 minutes after injection. By 20
      minutes after injection, diphenhydramine diameter of analgesia was significantly
      (p < 0.05) larger than placebo but significantly less than buffered lidocaine. By
      30 minutes after injection, diphenhydramine diameter of analgesia was equivalent
      to placebo whereas buffered lidocaine and lidocaine diameters were still
      significantly (p < 0.05) larger than placebo. Diphenhydramine injection resulted
      in numbness that lasted significantly (p < 0.05) longer than other study
      solutions whereas buffered lidocaine and lidocaine injections resulted in
      numbness that lasted significantly longer than placebo. Diphenhydramine injection
      resulted in hyperesthesia that lasted for 2 or more days in 12 of the volunteers.
      CONCLUSION: There is a reduction of infiltration pain using buffered lidocaine as
      opposed to lidocaine and diphenhydramine. Although lidocaine injection resulted
      in a slightly faster spread of analgesic diameter, buffered lidocaine was
      equivalent to lidocaine from minute 2 until minute 30. Therefore, to obtain
      optimal anesthetic conditions, we recommend that buffered lidocaine be given 2
      minutes before performing catheterization, whereas diphenhydramine should be
      given 5 minutes before catheterization, but only when buffered lidocaine cannot
      be used.

PMID- 12208438
TI  - Effects of combining midazolam and barbiturate on the response to tracheal
      intubation: changes in autonomic nervous system.
AB  - STUDY OBJECTIVE: To investigate the effects on the autonomic nervous system of
      anesthesia induction with a combination of midazolam and barbiturate using plasma
      catecholamine concentration and heart rate (HR) variability in comparison with
      the induction with barbiturate alone. DESIGN: Prospective study. SETTING:
      Operating room of a university hospital. PATIENTS: 40 ASA physical status I and
      II patients aged 30 to 70 years, who were scheduled for general anesthesia.
      INTERVENTIONS: Anesthesia was induced with 0.1 mg/kg midazolam followed by 3
      mg/kg thiopental sodium (Midazolam-Barbiturate group) or thiopental 5 mg/kg
      (Barbiturate group) with 6 L/min oxygen. MEASUREMENTS: Arterial blood pressure
      (BP), HR, HR variability, and plasma concentrations of epinephrine and
      norepinephrine were measured. MAIN RESULTS: Blood pressure and HR increased in
      response to tracheal intubation in both groups, but the increase was
      significantly larger in the Barbiturate group. In the Barbiturate group, the high
      frequency component (HF) in HR variability increased significantly during
      intubation, whereas in the Midazolam-Barbiturate group, HF decreased
      continuously. The low-frequency component (LF)/HF ratio increased in both groups,
      with significantly higher values noted in the Barbiturate group. Plasma
      epinephrine concentrations decreased before intubation and increased in response
      to tracheal intubation in the Barbiturate group. Finally, plasma norepinephrine
      concentrations increased in response to tracheal intubation only in the
      Barbiturate group. CONCLUSIONS: Anesthesia induction with a combination of
      midazolam-thiopental was effective in reducing hemodynamic and cardiac autonomic
      nervous system responses to tracheal intubation in comparison with the
      conventional induction with thiopental alone.

PMID- 12208439
TI  - Retrospective evaluation of unanticipated admissions and readmissions after same
      day surgery and associated costs.
AB  - STUDY OBJECTIVE: To determine the rate of unanticipated admissions and
      readmissions, and to characterize the associated reasons and costs. DESIGN:
      Retrospective medical records database analysis. SETTING: University teaching
      hospital. PATIENTS: Any patient undergoing same day surgery (SDS) during a 12
      month period. MEASUREMENTS: All nonelective return visits to the hospital within
      30 days and the reasons for return were identified. MAIN RESULTS: There were a
      total of 20,817 patients who underwent SDS in 1999; 1,195 (5.7%) of these
      returned to the hospital within 30 days or were admitted directly after surgery.
      Of those unanticipated admissions and readmissions, 313 (1.5%) were directly
      related to the original SDS procedure. The mean age of these patients was 51
      years, 164 (52%) were female, and 266 (85%) were Caucasian. Pain was the most
      commonly reported reason for return, occurring in 120 (38%) patients who had an
      unanticipated admission or readmission. After controlling for SDS volume, the
      general surgery service had the highest rate of unanticipated admissions or
      readmissions (3.2%), followed by otolaryngology (3.1%) and urology (2.9%). Of the
      120 patients returning with unanticipated admissions and readmissions due to
      pain, 46 (38%) had orthopedic procedures during their index SDS. Mean charges for
      patients with unanticipated admissions and readmission due to pain were $1,869 +/
      $4,553 per visit, whereas charges for nonpain related readmissions were $12,000
      +/- $36,886. CONCLUSION: At our teaching institution, approximately 1.5% of
      patients undergoing outpatient ambulatory surgery return within 30 days due to
      problems directly related to the original surgical procedure. Pain accounted for
      more than one third of return visits, incurring significant costs. Efforts to
      manage pain should focus not only on pain in the hospital but also anticipation
      of pain-related issues on discharge.

PMID- 12208440
TI  - The economic impact of opioids on postoperative pain management.
AB  - STUDY OBJECTIVE: To evaluate the consequences of opioid use for postoperative
      pain management and the degree to which these consequences may be reduced or
      minimized with opioid-sparing or opioid-replacement techniques. DESIGN:
      Literature review relating to the economics of postoperative pain management.
      Comparisons between opioids and opioid-sparing techniques were identified and
      selected for study. MEASUREMENTS AND MAIN RESULTS: Studies evaluating overall
      economic impacts or surrogate outcomes (e.g., resource use or recovery
      milestones) showed benefits with opioid-sparing therapies. CONCLUSIONS: Opioids
      will likely remain an integral part of postoperative pain management, but side
      effects increase the costs of care. The challenge is to identify situations where
      opioid-sparing techniques improve surrogate economic measurements and decrease
      overall hospital costs.

PMID- 12208441
TI  - Spontaneous pneumothorax during laparoscopic adrenalectomy secondary to a
      congenital diaphragmatic defect.
AB  - Despite its obvious benefits, laparoscopic surgery is not free of complications.
      It may cause significant physiologic changes and technical mishaps. Pneumothorax
      has been described as a complication of almost any type of laparoscopic surgery.
      We report a case of tension pneumothorax during laparoscopic adrenalectomy
      secondary to a congenital diaphragmatic defect and describe our treatment.

PMID- 12208442
TI  - Spontaneous rupture of uterus.
AB  - Spontaneous rupture of the uterus is a life-threatening obstetrical emergency.
      Diagnosis may be delayed because of the bizarre presentation or absence of
      significant pain and tenderness, which could have been masked by the analgesic
      medications used during labor. We present a case of spontaneous rupture in a
      multigravid female who was undergoing oxytocin-augmented labor while receiving
      epidural analgesia. She had had no previous cesarean deliveries or uterine
      surgery. Half an hour after an initial complaint of left inguinal pain, which was
      thought to be related to a patchy epidural block, she presented with changes in
      vital signs and significant fetal decelerations. At emergent cesarean section, a
      uterine rupture was noted. The uterine rupture extended down to the left vaginal
      angle, was not reparable and a hysterectomy was performed. The fetus survived.

PMID- 12208443
TI  - Which syringe did I use? Anesthesiologist confusion and potential liability for a
      medical error.

PMID- 12208444
TI  - Preoperative stress testing: new guidelines.
AB  - To date, there are no well controlled trials in the literature that demonstrate
      an outcome benefit using stress testing as a screening procedure before
      noncardiac surgery. Perioperative beta-blockade significantly decreases morbidity
      and mortality, and thus reduces any potential benefit stress testing may have in
      identifying patients who may advance to more invasive treatment. Preoperative
      percutaneous coronary intervention has unproven perioperative benefit, and
      coronary artery bypass graft carries risks that often offset the risk of
      noncardiac surgery. Unless an outcome benefit from cardiac testing and procedures
      can be demonstrated in a properly designed trial, their use should generally be
      restricted to situations in which symptoms or other cardiac findings warrant
      cardiac evaluation and treatment, regardless of upcoming surgery.

PMID- 12208445
TI  - Prolonged neuromuscular block due to cholinesterase depletion by plasmapheresis.
AB  - Plasmapheresis is a well-known therapeutic procedure for several medical
      conditions in which removal of circulating antibodies or albumin-bound toxins is
      desired. Circulating plasma cholinesterase enzyme levels are also depleted with
      plasmapheresis. This action causes patients to be susceptible to prolonged
      neuromuscular blockade when neuromuscular blocking drugs that are metabolized by
      this enzyme are used. We describe a case of prolonged neuromuscular blockade
      following succinylcholine and mivacurium administration in a 24-year-old renal
      transplant patient undergoing repeated plasmapheresis for recurrence of focal
      segmental glomerulosclerosis and acute vascular rejection. Serum and plasma
      cholinesterase levels were less than 20% of normal at the time of the event. The
      patient had spontaneous recovery after 12 hours of conservative supportive care.
      She tolerated a similar procedure uneventfully two weeks later when she was not
      taking plasmapheresis. Anesthesiologists should be aware of plasmapheresis as a
      mechanism for plasma cholinesterase depletion when using neuromuscular blocking
      drugs that are metabolized by this enzyme.

PMID- 12208447
TI  - A comparison of Internet usage between two residency programs in the United
      Kingdom and the United States.
AB  - STUDY OBJECTIVE: To survey the pattern of use and availability of the Internet
      among anesthesia residents. DESIGN: Survey questionnaire. SETTING: University
      hospital. MEASUREMENTS: A postal questionnaire of Internet attitudes and usage
      was sent to trainees in Anesthesiology in two training programs: the University
      of New Mexico, Albuquerque, NM (UNM) and the North West Regional Health
      Authority, Manchester, UK (NWR). A repeat questionnaire was sent to nonresponders
      after 4 weeks. Telephone interviews were conducted with hospital administration
      to determine availability and cost of the Internet. MAIN RESULTS: Response rates
      were 67% (82/122) from the NWR and 83% (25/31) from UNM. Compared with NWR,
      residents at UNM used the Internet longer for general (median 3 vs. 2 yrs; p <
      0.001) and medical (median 2 vs. 1.2 yrs; p < 0.001) purposes. All (31/31) UNM
      trainees and 73% (89/122) of NWR trainees had Internet access. More NWR trainees
      who had Internet access at work (60/61; 98%) used it for medically related
      purposes than those without work access (17/21, 81%; p < 0.001). More UNM
      trainees (19/25; 76%) accessed web sites other than those of official national
      organizations than did NWR trainees (40/82, 49%; p = 0.046). Approximately 75% of
      all trainees access web sites of the Association of Anesthetists and Royal
      College of Anesthetists (in the NWR) the American Society of Anesthesiologists
      (ASA) and American Board of Anesthesiology (in UNM) and online journals. The most
      popular sites were GASNET (Global Anesthesiology Server Network; NWR) and ASA
      (American Society of Anesthesiologists; UNM). Both UNM and NWR trainees perceived
      the Internet as supplying useful and accurate information. CONCLUSIONS: If the
      reported survey results are representative of Internet use among anesthesia
      residents in the United States and UK, Internet access at work is associated with
      greater Internet use for medical purposes, perhaps in part because residents
      perceive it to be a convenient and accurate resource.

PMID- 12208448
TI  - Learning by computer simulation does not lead to better test performance than
      textbook study in the diagnosis and treatment of dysrhythmias.
AB  - STUDY OBJECTIVE: To compare computer-based learning with traditional learning
      methods in studying advanced cardiac life support (ACLS). DESIGN: Prospective,
      randomized study. SETTING: University hospital. MEASUREMENTS: Senior medical
      students were randomized to perform computer simulation and textbook study. Each
      group studied ACLS for 150 minutes. Tests were performed 1 week before,
      immediately after, and 1 week after the study period. Testing consisted of 20
      questions. All questions were formulated in such a way that there was a single
      best answer. Each student also completed a questionnaire designed to assess
      computer skills, as well as satisfaction with and benefit from the study
      materials. MAIN RESULTS: Test scores improved after both textbook study and
      computer simulation study in both groups, although the improvement in scores was
      significantly higher for the textbook group only immediately after the study.
      There was no significant difference between groups in their computer skill and
      satisfaction with the study materials. The textbook group reported greater
      benefit from study materials than did the computer simulation group. CONCLUSIONS:
      Studying ACLS with a hard-copy textbook may be more effective than computer
      simulation for acquiring simple information during a brief period. However, the
      difference in effectiveness is likely transient.

PMID- 12208449
TI  - Abstracts of the 9th International Child Neurology Congress and the 7th Asian and
      Oceanian Congress of Child Neurology. September 20-25, 2002, Beijing, China.

PMID- 12208451
TI  - Synthesis and pharmacological profile of 6-methyl-3-isopropyl-2H-1,2-benzothiazin
      4(3H)-one 1,1-dioxide derivatives: non-steroidal anti-inflammatory agents with
      reduced ulcerogenic effects in the rat.
AB  - The new anti-inflammatory agents 6-methyl-3-isopropyl-2H-1,2-benzothiazin-4(3H)
      one 1,1-dioxide 6a and its analogues 6b-f were synthesized from L-valine. All
      compounds were characterized by physical, chemical and spectral studies.
      Preliminary pharmacological evaluation of the resulting products showed that
      compounds 6a-f (5-20 mg/kg, i.p.) are active anti-inflammatory agents in
      carrageenan-induced rat paw oedema assay in albino rats, and their effects are
      comparable to that of piroxicam (5 mg/kg, i.p.), used as a reference drug. The
      nature of the substituents on the sulfonamide nitrogen and those on position
      three had a pronounced effect on the anti-inflammatory activity. Studies of
      structure-activity relationships have led to selection of compound 2,6-dimethyl-3
      isopropyl-1,2-benzothiazin-3,4-diol 1,1-dioxide 6 f which exhibited the most
      potent activity (61.7% inhibition at 5 mg/kg, i.p. and ED(50)=4.5 mg/kg, i.p.).
      Comparison of the gastrointestinal safety of compounds 6a-f with that of
      piroxicam showed a far better tolerability for our products. This comparison was
      based on the ulcer index and the pH of gastric content.

PMID- 12208452
TI  - The influence of particles of a minor component on the matrix strength of sodium
      chloride.
AB  - This paper deals with the matrix strength of sodium chloride particles in pure
      sodium chloride tablets and in tablets compressed from binary mixtures of sodium
      chloride with low concentrations of pregelatinised starch. Because this study
      concerns the strength of the sodium chloride matrix, the tablet strength is
      reflected as a function of the sodium chloride volume fraction in the tablet.
      Starch particles in the mixture tablets decrease the sodium chloride volume
      fraction-tensile strength relationship compared with that of pure sodium chloride
      tablets. To determine the contribution of the sodium chloride matrix to the
      tablet strength, the starch particles were removed from the mixture tablets by
      heat treatment. Determination of the strengths of these heat-treated tablets
      reveals that the sodium chloride matrix strength determines the tablet strength
      of mixture tablets containing a single matrix of sodium chloride particles. The
      decrease of the sodium chloride matrix density in the three different tablets
      (pure sodium chloride tablets, mixture tablets and heat-treated tablets) is
      reflected by an increase of the median pore size. The matrix in sodium chloride
      tablets shows a higher tensile strength to median pore size relation than the
      matrices in the mixture and heat-treated tablets. Based on calculations according
      to the theory of elastic-brittle fracture, it is suggested that the initial
      presence of starch particles during tablet compaction causes the pores in the
      matrices of the mixtures and heat-treated tablets to be relatively more flat and
      longer. These pores weaken the sodium chloride matrix in the mixture and heat
      treated tablets to a larger extent than the shorter, more spherical pores formed
      during compaction of pure sodium chloride.

PMID- 12208453
TI  - Effects of nonionic surfactants on membrane transporters in Caco-2 cell
      monolayers.
AB  - The objectives of this study were (1) to investigate the transporter inhibition
      activity of three nonionic surfactants on P-glycoprotein, the human intestinal
      peptide transporter, and the monocarboxylic acid transporter in Caco-2 cell
      monolayers, and (2) to evaluate the role of membrane fluidity and protein kinase
      C in surfactant-induced transporter inhibition. All three surfactants inhibited P
      glycoprotein (P-gp). Over a range from 0 to 1 mM, Tween 80 and Cremophor EL
      increased apical-to-basolateral permeability (AP-BL) and decreased basolateral-to
      apical (BL-AP) permeability of the P-gp substrate rhodamine 123. Vitamin E TPGS's
      effect was equally large, but essentially only reduced the BL-AP permeability of
      rhodamine 123, and did so at a vitamin E TPGS concentration of only 0.025 mM.
      These P-gp inhibition effects would appear to be related to these excipients'
      modulation of membrane fluidity, where Tween 80 and Cremophor EL fluidized cell
      lipid bilayers, while vitamin E TPGS rigidized lipid bilayers. However, among the
      three surfactants, only Tween 80 inhibited the peptide transporter, as measured
      by glycyl sarcosine permeability. Likewise, only Cremophor EL inhibited the
      monocarboxylic acid transporter, as measured by benzoic acid permeability.
      Nevertheless, at least one of these three surfactants inhibited each P-gp, the
      human intestinal peptide transporter, and the monocarboxylic acid transporter. A
      common functional feature of these three surfactants was their ability to
      modulate fluidity, although results indicate that even strong membrane fluidity
      modulation alone was not sufficient to reduce transporter activity. N-octyl
      glucoside, a nonionic surfactant that did not modulate membrane fluidity, did not
      affect transporter functioning. Protein kinase C inhibitors failed to affect
      rhodamine 123 and glycyl sarcosine permeability, suggesting protein kinase C
      inhibition was not the mechanism of transporter inhibition. These results suggest
      that surfactants can inhibit multiple transporters but that changes in membrane
      fluidity may not be a generalized mechanism to reduce transporter activity.

PMID- 12208454
TI  - Characterization of the complexes of furosemide with 2-hydroxypropyl-beta
      cyclodextrin and sulfobutyl ether-7-beta-cyclodextrin.
AB  - The purpose of this study was to prepare and characterize complexes of furosemide
      with 2-hydroxypropyl-beta-cyclodextrin (2-HP-beta-CD) and sulfobutyl ether-7-beta
      cyclodextrin (SBE-7-beta-CD). Solid complexes of furosemide with 2-HP-beta-CD and
      SBE-7-beta-CD were prepared by using both a freeze-drying and kneading method.
      Physical mixtures were prepared for comparison. The inclusion complexes were
      characterized by differential scanning calorimetry, X-ray diffractometry (XRD)
      and 1H nuclear magnetic resonance spectroscopy (1H-NMR). 1H-NMR, and especially
      the use of the two-dimensional ROESY spectrum, was used to determine the position
      of the furosemide molecule inside the cyclodextrin cavity. 1H-NMR studies showed
      that furosemide fit into the cyclodextrin torus cavity with its furane ring
      nearest to the primary hydroxyl side.

PMID- 12208455
TI  - Inhibitory effect of vanillin-like compounds on respiration and growth of
      adenocarcinoma TA3 and its multiresistant variant TA3-MTX-R.
AB  - The effects of some imine and amine derivatives of vanillin on the respiration
      rate of mouse mammary adenocarcinoma TA3 line, its multiresistant variant TA3-MTX
      R line and mouse hepatocytes, together with their respective mitochondrial
      fractions, are described. These derivatives inhibit respiration in both tumour
      cell lines more effectively than vanillin in the absence or presence of the
      uncoupler CCCP. Since both types of derivatives block the electron flow, mainly
      through the NADH-CoQ span, they behave as oxidative phosphorylation inhibitors.
      Thus, they prevent ATP synthesis and alter cellular processes requiring energy,
      which would lead to cellular death. Amine derivatives of vanillin present a
      similar effect on both tumour cell lines, being amine C the most efficient
      inhibitor. Moreover, mouse hepatocytes are about 4-fold less sensitive to amine C
      than tumour cells. These amine derivatives are better inhibitors than the
      corresponding imines; probably because they should interact better with the
      respiratory chain reaction site.

PMID- 12208456
TI  - Characterization of quinidine 3-hydroxylation as a probe for the CYP 3A enzyme
      using a novel capillary electrophoresis technique.
AB  - Capillary electrophoresis (CE) with a direct injection technique was used to
      characterize the formation of (3S)-3-hydroxyquinidine (3-OHQ) as a probe for the
      CYP 3A isoenzymes in rat liver microsomes. Detection was performed either in the
      absorbance mode or by employing laser-induced fluorescence (LIF) detection.
      Michaelis-Menten parameters (mean values+/-S.D.) K(m) and V(max) for the
      formation of 3-OHQ from the probe drug quinidine sulfate (QS) in rat liver
      microsomes were 37+/-4.6 micro g/ml (47.1+/-5.9 micro M) and 321+/-4 ng/mg/h
      (942+/-11.7 pmol/mg/h), respectively. Inhibition studies were performed to
      evaluate the specificity of 3-OHQ as a probe for the CYP 3A enzyme. Ketoconazole
      and fluconazole were found to be inhibitors of 3-OHQ formation and exhibited K(i)
      values of 0.19 and 20.1 micro M, respectively. Inhibition with the weak
      inhibitor, erythromycin could only be estimated using LIF detection due to lack
      of sensitivity in the absorbance mode. The formation of 3-OHQ in rat liver
      microsomes can be used as a model for the screening of the CYP 3A enzyme. Direct
      injection, ensures faster analysis time due to the lack of sample preparation and
      the low volume capabilities of the technique makes it attractive for the
      screening of a large number of compounds.

PMID- 12208457
TI  - Improved stability and release control of levodopa and metaraminol using ion
      exchange fibers and transdermal iontophoresis.
AB  - Achievement of controlled drug delivery and stability of drugs during storage is
      a problem also in transdermal drug delivery. The objective of this study was to
      determine, whether an easily oxidized drug, levodopa, could be stabilized during
      storage using pH-adjustment and ion-exchange fibers. Controlled transdermal
      delivery of the zwitterionic levodopa was attempted by iontophoresis and ion
      exchange fiber. Ion-exchange kinetics and transdermal permeation of a cationic
      (presumably more stable) model drug, metaraminol, were compared to the
      corresponding data of levodopa. Levodopa was rapidly oxidized in the presence of
      water, especially at basic pH-values. At acidic pH-values the stability was
      improved significantly. Ion-exchange group and the pH had a clear effect on the
      release of both the levodopa and metaraminol from the ion-exchange fiber. The
      adsorption/release kinetics of metaraminol were more easily controllable than the
      corresponding rate and extent of levodopa adsorption/release. Iontophoretic
      enhancement of drug permeation across the skin was clearly more significant with
      the positively charged metaraminol than with the zwitterionic levodopa. Ion
      exchange fibers provide a promising alternative to control drug delivery and to
      store drugs that are degraded easily.

PMID- 12208458
TI  - The effect of experimental design on the modeling of a tablet coating formulation
      using artificial neural networks.
AB  - The aim of this study was to investigate the effect of experimental design
      strategy on the modeling of a film coating formulation by artificial neural
      networks (ANNs). Box-Behnken, central composite and pseudo-random designs of 102,
      90 and 100 simulated records, respectively were used to train a multilayer
      perceptron (MLP) ANN comprising six input and two output nodes separated by a
      single hidden layer of five nodes. Network over-training was limited by using a
      test set of 40 pseudo-randomly distributed records. The models were validated
      using a set of 60 pseudo-randomly distributed records. Crack velocity was highly
      curved with respect to pigment particle size and size distribution. Similarly,
      film opacity was highly curved in response to pigment concentration and film
      thickness. The Box-Behnken and central composite designs generated models that
      were unable to predict crack velocity and showed extensive bias in prediction of
      film opacity. The pseudo-random design was unable to predict crack velocity of
      the test data set but yielded acceptable predictions for the validation set. Film
      opacity was well predicted by the pseudo-random design model. The poor predictive
      ability of the Box-Behnken and central composite models was attributed to poor
      interpolation of the high curvature of the response surfaces. In contrast, the
      pseudo-random design mapped the interior of the design space allowing improved
      interpolation and predictive ability. It is concluded that Box-Behnken and
      central composite experimental designs are inappropriate for ANN modeling of
      highly curved responses and that extensive internal mapping of the design space
      is essential to generate predictive ANN models.

PMID- 12208459
TI  - Kinetics of zinc transport in vitro in rat small intestine and colon: interaction
      with copper.
AB  - The present study was planned to investigate the kinetic transport of zinc, in
      the intact intestine of the rat, in order to establish if more than one
      transporter is involved as well as the existence of a preferent sector in the
      cation uptake. Using an in vitro technique, the influx of zinc across the brush
      border membrane in three sectors of the small intestine (proximal, mid and
      distal) and in the colon of the rat was measured at six different concentrations
      (from 0.0007 to 11 mM). The kinetic study showed that intestinal transport of
      zinc occurs by a saturable process in the small intestine. The K(m) value
      obtained in the proximal segment (10.78+/-4.40 mM) is clearly higher than those
      obtained in the mid and distal segments (1.94+/-0.39 and 3.04+/-0.44 mM,
      respectively). The same occurs with the J(max) values. These results seem to
      indicate that more than one transporter may be implicated in zinc transport. In
      colon the most probable mechanism is non-saturable diffusion, the diffusive
      permeability, P, being 2.95.10(-7)+/-0.43.10(-7) cm/h. The statistical comparison
      of the fluxes indicated that, on the whole, there is not a well defined preferent
      sector in zinc transport. Additionally, the influence of copper on zinc
      transport, in three sectors of the small intestine, has been evaluated
      quantifying the influx of zinc at 0.037 mM in the absence and presence of three
      different concentrations of copper. The results showed that copper significantly
      reduced the influx of zinc, in the three sectors studied, in a concentration
      dependent manner.

PMID- 12208460
TI  - Isosorbide-based aspirin prodrugs. II. Hydrolysis kinetics of isosorbide
      diaspirinate.
AB  - Aspirin prodrugs have been intensively investigated in an effort to produce
      compounds with lower gastric toxicity, greater stability or enhanced percutaneous
      absorption, relative to aspirin. This report describes the hydrolysis kinetics
      and aspirin release characteristics of isosorbide diaspirinate (ISDA), the
      aspirin diester of isosorbide. ISDA underwent rapid hydrolysis when incubated in
      phosphate buffered human plasma solutions (pH 7.4) at 37 degrees C, producing
      appreciable quantities of aspirin. In 30% human plasma solution the half-life was
      1.1 min and 61% aspirin was liberated relative to the initial ester
      concentration. The hydrolysis kinetics of ISDA were monitored in aqueous solution
      at 37 degrees C over the pH range 1.03-9.4. The aqueous hydrolysis followed
      pseudo-first-order kinetics over several half-lives at all pH values, resulting
      in a U-shaped pH rate profile. Salicylate esters and salicylic acid were formed
      during these processes. The hydrolysis characteristics of ISDA were also
      investigated in pH 7.4 phosphate buffered solutions containing alpha-chymotrypsin
      [EC 3.1.1.1] (t(1/2)=200.9 min), carboxyl esterase [EC 3.1.1.1] (t(1/2)=31.5
      min), human serum albumin (t(1/2)=603 min), purified human serum
      butyrylcholinesterase [EC 3.1.1.8] (80 micro g/ml; t(1/2)=9.4 min; 55% aspirin),
      purified horse serum butyrylcholinesterase (100 micro g/ml; t(1/2)=1.85 min;11%
      aspirin) and in 10% human plasma solution in the presence of physostigmine (3
      micro M). The results indicate that a specific enzyme present in human plasma,
      probably human butyrylcholinesterase, catalyses aspirin release from isosorbide
      diaspirinate.

PMID- 12208461
TI  - Spray-dried indomethacin-loaded polyester nanocapsules and nanospheres:
      development, stability evaluation and nanostructure models.
AB  - The industrial development of polymeric nanoparticle suspensions, as drug
      delivery systems, is limited due to the problems in maintaining stability of
      suspensions. In this work, a spray-drying technique was applied to dry
      nanocapsule and nanosphere suspensions prepared by nanoprecipitation of
      polyesters using SiO(2) as adjuvant. Powders obtained from nanocapsules presented
      stable drug recoveries and morphological characteristics after 5 months. For
      nanocapsules, nanostructures around 200 nm were observed by scanning electron
      microscopy (SEM) on the surface of microparticles of SiO(2), whereas for the
      nanosphere formulation, nanostructures with a reduced diameter (60-90 nm) were
      observed, despite the particle sizes of each original suspension being similar,
      when measured by photon correlation spectroscopy (PCS). In order to investigate
      the morphological aspects of nanocapsule and nanosphere powders, several
      nanosphere formulations were spray-dried using different concentrations of SiO(2)
      and a comparative study of the different colloidal systems (nanocapsules,
      nanospheres, nanoemulsion or nanodispersion) was carried out by PCS. SEM analyses
      showed that nanostructures with reduced diameter are formed independently of the
      adjuvant concentration. The dynamic properties of these systems allowed to
      suggest that the structure of the nanosphere particle (polymer, sorbitan
      monostearate and polysorbate 80) was a polymeric matrix dispersing the sorbitan
      monostearate which, when submitted to the spray-drying process in the presence of
      SiO(2), gave nanostructures presenting diameters around 80 nm covering the
      microparticles due to the release of lipophilic surfactant from the polymeric
      matrix.

PMID- 12208462
TI  - Lactose modifications enhance its drug performance in the novel multiple dose
      Taifun DPI.
AB  - Drug-carrier particle interactions greatly affect the detachment of drug from the
      carrier in inhalation powders. In this study, a novel multiple dose, reservoir
      based Taifun was used as a dry powder inhaler, and the effects of carrier
      physical properties were evaluated on the pulmonary deposition of budesonide,
      along with physical stability of the inhalation powder. In this study, untreated
      commercial preparation of alpha-lactose monohydrate, highly amorphous spray dried
      lactose, crystallized spray dried lactose, Flowlac-100 and Flowlac-100 mixed with
      crystalline micronized lactose were used as carriers. Dry powder formulations
      were prepared by the suspension method, where the budesonide-carrier ratio was
      1:15.1 (w/w). Carriers and formulations were initially characterized, and again
      after 1 month's storage at 40 degrees C/75% RH. The physical properties of the
      carriers strongly affected the pulmonary deposition of budesonide and the
      physical stability of the inhalation powder. Initially, amorphous contents of the
      carriers were 0-64%, but spontaneous crystallisation of the amorphous lactose
      occurred during storage and, thus all carriers were 100% crystalline after
      storage. When compared to an untreated alpha-lactose monohydrate, the highly
      amorphous spray dried lactose and Flowlac-100 did not improve aerosol performance
      of the inhalation powder. When crystalline spray dried lactose was used as a
      carrier, the highest RF% values were achieved, and RF % values did not alter
      during storage but the emitted budesonide dose was lower than the theoretical
      dose. When Flowlac-100 mixed with crystalline micronized lactose was used as a
      carrier, the emitted budesonide dose was close to the theoretical dose, and high
      RF % values were achieved but these changed during storage.

PMID- 12208463
TI  - Drug release profiles from and degradation of a novel biodegradable polymer, 2,2
      bis(2-oxazoline) linked poly(epsilon -caprolactone).
AB  - In the present study, poly (epsilon -caprolactone) (PCL) was modified by
      introducing oxamide groups into PCL (PCL-O). The degradation (decrease in
      molecular weight) and erosion (weight loss) of PCL and PCL-O films were studied
      in PBS (pH 7.4, USP XXIV, 37 degrees C, 26 weeks incubation). The release rates
      of guaifenesin (M(w) 198.2), griseofulvin (M(w) 352.8), timolol (M(w) 332.4),
      sodium salicylate (M(w) 160.1) and FITC-dextran (M(w) 4400) from PCL and PCL-O
      preparations (solvent cast films, compression-molded plates, midi injection
      molded rods and microparticles) were examined in PBS (pH 7.4, 37 degrees C). The
      degradation rate of PCL-O film was faster than that of PCL film while no erosion
      was observed for either film. When compared to the corresponding drug release
      from PCL films, the release rates of low molecular weight drugs (M(w)< or =352.8)
      from PCL-O films were comparable, their releases from both films following
      closely square-root-of-time kinetics. These results indicate that the oxamide
      groups had no substantial effect on the release of the low molecular weight
      drugs. The exception was sodium salicylate which was released faster from PCL-O
      film. However, FITC-dextran release was notably faster from PCL-O microparticles
      than from those made of PCL. FITC-dextran release was a combination of diffusion
      and polymer degradation and thus, the faster degradation of PCL-O enhanced the
      release of FITC-dextran. In conclusion, the effects of the oxamide groups on drug
      release profiles were dependent on the drug release mechanisms.

PMID- 12208464
TI  - Lowering plasma homocysteine with folic acid in cardiovascular disease: what will
      the trials tell us?

PMID- 12208465
TI  - Increased intracellular calcium transients by calmodulin antagonists
      differentially modulate tumor necrosis factor-alpha-induced E-selectin and ICAM-1
      expression.
AB  - We investigated the role of intracellular calcium ([Ca(2+)](i)) in adhesion
      molecule expression in human umbilical vascular endothelial cells (HUVECs).
      Calmodulin (CaM) antagonists, W-7, trifluoperazine and chlorpromazine, triggered
      a rise in [Ca(2+)](i) in HUVECs. In the presence of extracellular Ca(2+),
      thapsigargin pretreatment completely prevented W-7-stimulated increase in
      [Ca(2+)](i), indicating that increase is attributable to the release of Ca(2+)
      from internal stores. The increased [Ca(2+)](i) acted as a second messenger to
      enhance tumor necrosis factor-alpha (TNF-alpha)-induced E-selectin and suppress
      intercellular cell adhesion molecule (ICAM-1) expression. Preincubation of HUVECs
      with the Ca(2+) chelator 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'
      tetraaceticacetomethyl ester blocked W-7-mediated effects on E-selectin and ICAM
      1. The W-7 effects were paralleled by changes in the respective mRNAs, suggesting
      regulation at a pretranslational level. These findings indicate that CaM
      regulated [Ca(2+)](i) in HUVECs may play an important role in controlling
      expression of endothelial adhesion molecules involved in atherogenesis.

PMID- 12208466
TI  - Combined effects of cholesterol reduction and apolipoprotein A-I expression on
      atherosclerosis in LDL receptor deficient mice.
AB  - Reduction of total and LDL cholesterol reduces atherosclerosis and clinical
      cardiovascular events. High density lipoprotein (HDL) cholesterol levels have a
      strong inverse association with atherosclerosis, and overexpression of
      apolipoprotein A-I (apoA-I), the major protein component of HDL, reduces
      atherosclerosis in hypercholesterolemic animals. However, little is known about
      the potential for additive or synergistic effects between cholesterol reduction
      and apoA-I overexpression on atherosclerosis. In the current study, we tested the
      hypothesis that significant reduction of plasma cholesterol combined with
      overexpression of apoA-I would reduce atherosclerosis to a greater extent than
      either one alone. We used somatic gene transfer of the LDL receptor (to induce
      cholesterol reduction) and apoA-I in LDL receptor deficient mice fed a Western
      type diet and compared the combination to expression of each gene alone and to
      controls. Atherosclerosis was quantitated using two independent methods, by en
      face analysis of the entire aorta and by cross-sectional analysis of the aortic
      root. Although the reduction of cholesterol was transient, expression of the LDL
      receptor alone significantly reduced atherosclerosis by 45% in the aorta and 44%
      in the aortic root compared with controls. Overexpression of human apoA-I alone
      reduced atherosclerosis by 42% in the aorta and 44% in the aortic root compared
      with controls. Co-expression of the LDL receptor with apoA-I resulted in
      significantly higher levels of apoA-I than expression of apoA-I alone. Although
      co-expression of the LDL receptor and apoA-I reduced atherosclerosis by 37% in
      the aorta and 32% in the aortic root compared with controls, the reduction in
      atherosclerosis was no different than that seen with expression of the LDL
      receptor alone or apoA-I alone. In summary, in this relatively short-term murine
      model, simultaneous reduction of cholesterol and expression of apoA-I was
      associated with higher levels of apoA-I than expression of apoA-I alone but did
      not result in greater reduction in atherosclerosis compared with either one
      alone.

PMID- 12208467
TI  - Changes in gene expression in atherosclerotic plaques analyzed using DNA array.
AB  - A better understanding of atherogenesis at the level of gene expression could
      lead to the identification of new therapeutic strategies for vascular diseases.
      With DNA array technology, it is possible to identify multiple, simultaneous
      changes in gene expression in small tissue samples from atherosclerotic arteries.
      We analyzed gene expression in normal arteries and in immunohistologically
      characterized human advanced atherosclerotic lesions using an array of 18376 cDNA
      fragments. The array method was first validated by detecting a group of genes
      (n=17) that were already known to be connected to atherogenesis. These genes
      included e.g. Apolipoprotein E, CD68, TIMP and phospholipase D. Next we detected
      75 differentially expressed genes that were previously not connected to
      atherogenesis. A subgroup of genes involved in cell signaling and proliferation
      was selected for further analyzes with in situ hybridization and RT-PCR which
      confirmed array results by showing induction in advanced lesions of Janus kinase
      1 (JAK-1) which is an important signaling molecule in activated macrophages; VEGF
      receptor-2 which mediates angiogenic and vasculoprotective effects of VEGF; and
      an unknown gene, which mapped on chromosome 19. It is concluded that DNA array
      technology enables fast screening of gene expression in small samples of
      atherosclerotic lesions. The technique will be useful for the identification of
      new factors, such as JAK-1 and VEGF receptor-2, which may play an important role
      in atherogenesis.

PMID- 12208468
TI  - Dietary supplementation with vitamins C and E prevents downregulation of
      endothelial NOS expression in hypercholesterolemia in vivo and in vitro.
AB  - Impaired endothelium-dependent vasodilation has been associated with decreased NO
      bioavailability in hypercholesterolemia. This study aimed to determine whether
      antioxidant vitamins C and E could improve hypercholesterolemia-derived
      endothelial dysfunction in the porcine model, and whether observed in vivo
      results could be reproduced in vitro by incubation of coronary endothelial cells
      (EC) in the presence of native low-density lipoproteins (LDL). Adult mini-pigs
      were fed standard (C), cholesterol rich (HC) or cholesterol rich diet
      supplemented with vitamins C and E (HCV). Endothelium-dependent blood flow
      increase in response to acetylcholine was determined. Endothelial nitric oxide
      synthase (eNOS) expression was measured in arterial samples and in EC incubated
      with LDL isolated from porcine plasma. Vasomotor response to acetylcholine in HC
      was significantly lower (P<0.05) than control and HCV. There was a significant
      (P<0.05) decrease in eNOS immunoreactivity in HC, compared with HCV and control.
      Native LDL from HC, but not from HCV, induced a significant decrease in eNOS
      expression. Vitamins C and E treatment improved the endothelium-dependent
      vasomotor capacity and prevented decreased expression of eNOS in
      hypercholesterolemic pigs. A similar effect could be demonstrated in vitro, by
      incubation of EC with native LDL, suggesting that the effect of physiologically
      modified LDL on eNOS could have a role in recovering vascular function.

PMID- 12208469
TI  - Prevention of LDL alpha-tocopherol consumption, cholesterol oxidation, and
      vascular endothelium dysfunction by polyphenolic compounds from red wine.
AB  - Red wine polyphenolic compounds (RWPCs) have been demonstrated to possess
      antioxidant properties, and several studies have suggested that they might
      constitute a relevant dietary factor in the protection from coronary heart
      disease. The aim of the present study was to determine further the mechanism by
      which RWPCs can prevent the formation of vasoactive compounds in oxidized LDL.
      RWPCs were obtained from the Cabernet-Sauvignon grape variety. Human LDL was
      oxidized in the presence of CuSO(4) (ox-LDL). Vascular reactivity studies were
      conducted on rabbit aortic rings. RWPCs significantly reduced the formation of 7
      beta-hydroxycholesterol and 7-ketocholesterol and in a lower extent the emergence
      of lysophosphatidylcholine in ox-LDL. The ability of RWPCs to prevent cholesterol
      oxide formation was directly dependent on the LDL alpha-tocopherol content. Once
      the LDL alpha-tocopherol has been consumed, RWPCs were no longer effective,
      indicating that RWPCs act by sparing endogenous alpha-tocopherol. As a
      consequence of the preservation of the endogenous alpha-tocopherol content of
      LDL, RWPCs could prevent the inhibition of the acetylcholine-mediated endothelium
      dependent relaxation of rabbit aorta which was linked to a direct effect on NO
      release. Independently of a treatment with ox-LDL, RWPC exerted a concentration
      dependent and persistent inhibitory effect on the norepinephrine-induced
      contraction of rabbit aorta. In conclusion, RWPCs can preserve a normal vascular
      reactivity by acting at different stages of the cascade that leads to lipid
      oxidation, endothelium dysfunction and vasospasm.

PMID- 12208470
TI  - Regulation of interleukin-8 expression by HMG-CoA reductase inhibitors in human
      vascular smooth muscle cells.
AB  - Interleukin-8 (IL-8) is a potent chemotactic factor that has been implicated in
      atherogenesis. HMG-CoA reductase inhibitors (statins) may reduce the
      cardiovascular risk and vulnerability of atherosclerotic plaque through nonlipid
      mechanisms such as inhibition of cytokine expression. In this study, we
      investigated the effects of statins on IL-8 synthesis in human vascular smooth
      muscle cells (VSMCs). Addition of angiotensin II (Ang II) increased IL-8
      production in VSMCs in a time (0-24 h)- and dose (10(-8)-10(-6) mol/l)-dependent
      manner with increased IL-8 mRNA accumulation. The Ang II type 1 receptor (AT1R)
      antagonist candesartan, but not the Ang II type 2 receptor (AT2R) antagonist
      PD123319, significantly blocked Ang II-induced IL-8 production. Addition of
      fluvastatin decreased the basal and Ang II-induced IL-8 production in VSMCs in a
      dose (10(-8)-10(-5) mol/l)-dependent manner with a decrease in IL-8 mRNA
      accumulation. The effect of fluvastatin on IL-8 production was completely
      reversed in the presence of mevalonate or geranylgeranyl-pyrophosphate, but not
      in the presence of squalene or farnesyl-pyrophosphate. Lipophilic cerivastatin
      also significantly decreased IL-8 production, while hydrophilic pravastatin
      showed no effect on IL-8 levels. In conclusion, we demonstrated for the first
      time that Ang II increased IL-8 production and fluvastatin decreased the basal
      and Ang II-induced IL-8 production in human VSMCs. These findings suggested that
      Ang II may exacerbate atherosclerosis through induction of IL-8 in VSMCs, while
      statins may exert therapeutic effects by modulating IL-8 synthesis in patients
      with atherosclerotic disease.

PMID- 12208471
TI  - Platelet and fibrinogen turnover at the exposed subendothelium measured over 1
      year after a balloon catheter de-endothelializing injury to the rabbit aorta:
      thrombotic eruption at the late re-endothelialization stage.
AB  - Balloon catheter de-endothelialization of the rabbit aorta in vivo causes a rapid
      release of thrombin and a consequent hemostatic response at the surface of the
      exposed subendothelium. Previously, we have compared the net fluxes of several
      hemostatic proteins from plasma into the exposed aorta subendothelium for up to
      600 days after injury. We now report the turnover of platelets, compared to
      fibrinogen, at the de-endothelialized aorta for up to 390 days after injury.
      Anesthetized NZW rabbits received either a de-endothelializing or a sham injury
      (controls) to their aortas. At a predetermined time (either 10 min before or up
      to 390 days after injury), each rabbit was infused with known quantities of
      rabbit (51)Cr-platelets and rabbit (125)I-fibrinogen; the radiolabels were
      allowed to circulate for 10 min before the rabbit was rapidly exsanguinated.
      Radioactivity measurements and tissue analysis revealed that at 10 min after
      balloon injury, approximately 165,000 platelets/mm(2) were associated with the
      aorta surface, and platelet turnover was 840/min/mm(2). Turnover had decreased to
      <200/min/mm(2) at 10-21 days but, from 65 to 390 days, had increased to
      approximately 1500/min/mm(2). In comparison, approximately 17 pmol of
      fibrinogen/cm(2) saturated the ballooned surface by 10 min after injury.
      Fibrinogen turnover at the aorta surface at 10 min after injury amounted to 0.2
      pmol/min/cm(2), increasing to 0.7 at 10 days but decreasing to 0.25 at 21 days.
      Between 65 and 390 days, fibrinogen turnover increased slowly to 1.3
      pmol/min/cm(2). Fibrinogen turnover at the surface of the aorta paralleled that
      within the intima-media over 390 days. Platelet and fibrin(ogen) deposits within
      the aorta wall increased over the 21-390 days interval as shown by
      immunostaining. The results are consistent with the re-endothelializing aorta
      tending to support thrombosis and ulceration in the late healing stage.

PMID- 12208472
TI  - Activation of human aortic endothelial cells by LDL from Type 1 diabetic
      patients: an in vitro study.
AB  - An altered interaction between circulating LDL and endothelial cells might be at
      the basis of the increased prevalence of atherosclerosis in diabetes mellitus.
      The aim of the present work was to investigate the effect of a short incubation
      period with LDL from Type 1 diabetic patients in good metabolic control on
      endothelial cells derived from human aorta (HAEC). Cultured HAEC were incubated
      for 3 h with culture medium alone (control HAEC), with native LDL from healthy
      subjects (control LDL), or with native LDL from Type 1 diabetic patients (Type 1
      LDL). After the incubation the following parameters were evaluated: endothelial
      cell nitric oxide synthase (NOS) activity, nitric oxide (NO) and peroxynitrite
      production, Na(+)/K(+)-ATPase and Ca(2+)-ATPase activities, intracellular Ca(2+)
      concentration and fluidity of the superficial part of the plasma membrane studied
      by 1-(4-trimethylaminophenyl)-6-phenyl-1,3,5-hexatriene (TMA-DPH). Moreover, we
      studied the cellular activation, evaluated by the fluid phase endocytosis of TMA
      DPH, and the microetherogeneity of the membrane surface, evaluated by dynamic
      fluorescence. HAEC incubated with control LDL showed compared with control HAEC:
      increased anisotropy and exponential lifetime of TMA-DPH, and enhanced TMA-DPH
      internalization. HAEC incubated with Type 1 LDL showed compared with both control
      HAEC and HAEC incubated with control LDL: (i) increased Na(+)/K(+)-ATPase and
      Ca(2+)-ATPase activities, and intracellular Ca(2+) concentration; (ii) increased
      NOS activity, NO and peroxynitrite production; (iii) increased anisotropy of TMA
      DPH; (iv) enhanced internalization of the probe. The exponential lifetime and the
      width of distribution of TMA-DPH were significantly increased by Type 1 LDL only
      in comparison with control HAEC. The results suggest that a short-term
      interaction with LDL from Type 1 diabetic patients causes alterations of the
      plasma membrane surface and of cellular functions in endothelial cells in a
      possibly atherogenic way.

PMID- 12208473
TI  - Chlamydia pneumoniae activates IKK/I kappa B-mediated signaling, which is
      inhibited by 4-HNE and following primary exposure.
AB  - Chlamydia pneumoniae may be involved in atherosclerosis by inducing inflammation
      as well as LDL oxidation. The transcription factor NF-kappa B is found in an
      active state in atherosclerotic lesions. This study examined the effect of C.
      pneumoniae exposure on the NF-kappa B system in human monocytic lineage cells.
      Short exposure to C. pneumoniae as well as chlamydial heat shock protein 60
      activated NF-kappa B, accompanied by increased cytokine production. Incubation
      with C. pneumoniae-induced depletion of I kappa B-alpha and later I kappa B
      epsilon which was preceded by I kappa B kinase complex activation. 4
      Hydroxynonenal, an aldehyde LDL oxidation product, was shown to inhibit C.
      pneumoniae induced NF-kappa B activation by preventing I kappa B
      phosphorylation/proteolysis. During long-term incubation with C. pneumoniae I
      kappa B-alpha returned to baseline, whereas the levels of I kappa B-epsilon and
      p65 were upregulated. Interestingly, long-term preincubation with C. pneumoniae
      selectively prevented restimulation by this microorganism, which appears to be at
      least partly facilitated by inhibition of I kappa B proteolysis. C. pneumoniae
      induced NF-kappa B activation as well as the inhibition of that effect under
      certain conditions may contribute to chronic inflammation with potential
      relevance to vascular disease.

PMID- 12208474
TI  - Transgenic overexpression of human lecithin: cholesterol acyltransferase (LCAT)
      in mice does not increase aortic cholesterol deposition.
AB  - Results from several atherosclerosis studies using morphometric procedures have
      proven controversial with regard to whether over-expression of human LCAT in
      transgenic (Tg) mice is atherogenic. The purpose of the present study was to
      determine the effect of 10-fold over-expression of human LCAT on aortic free and
      esterified cholesterol (EC) deposition as well as plasma lipoprotein cholesteryl
      ester (CE) fatty acid composition in mice fed an atherogenic diet containing
      cholic acid. C57Bl/6 (control) and human LCAT-Tg mice were fed chow or an
      atherogenic diet (15% of calories from palm oil, 1.0% cholesterol and 0.5% cholic
      acid) for 24 weeks before measurement of aortic cholesterol content. Compared
      with the chow diet, control and LCAT-Tg mice fed the atherogenic diet had a 2
      fold increase in plasma total, free and EC, a 7-fold increase in plasma apoB
      lipoprotein cholesterol, and a 40-50-fold increase in hepatic cholesterol
      content. The aortic EC content was increased in control (0.7 vs. 1.2 mg/g
      protein) and LCAT-Tg (0.3 vs. 1.5 mg/g protein) mice fed the atherogenic diet
      compared with those consuming the chow diet; however, there was no difference in
      aortic free (14.4+/-6.8 vs. 18.5+/-7.7 mg/g protein) or esterified (1.2+/-1.0 vs.
      1.5+/-1.2 mg/g protein) cholesterol content between atherogenic diet-fed control
      and LCAT-Tg mice, respectively. LCAT-Tg mice fed the atherogenic diet had a 2
      fold increase in the ratio of saturated+monounsaturated to polyunsaturated CE
      species in plasma apoB lipoproteins compared with control mice (9.4+/-2.4 vs.
      4.9+/-0.7). We conclude that over-expression of human LCAT in Tg mice fed an
      atherogenic diet containing cholic acid does not result in increased aortic
      cholesterol deposition compared with control mice, even though the CE fatty acid
      saturation index of plasma apoB lipoproteins was doubled.

PMID- 12208475
TI  - Peroxisome proliferator-activated receptor alpha and gamma agonists upregulate
      human macrophage lipoprotein lipase expression.
AB  - Peroxisome proliferator-activated receptors (PPARs) are transcriptional factors
      which mediate pleiotropic effects including regulation of genes involved in lipid
      metabolism and control of inflammation. In the present study, we measured the in
      vitro effects of PPAR alpha and gamma ligands on macrophage lipoprotein lipase
      (LPL) expression. Human monocyte-derived macrophages (MDM) were cultured for 1-3
      days in the presence of PPAR alpha and gamma ligands. At the end of these
      incubation periods, extracellular LPL immunoreactive mass/activity and LPL mRNA
      levels were measured. Incubation of human MDM with PPAR alpha and gamma ligands
      stimulated, in a time- and dose-dependent manner, human MDM LPL mass and
      activity. These agents also significantly increased macrophage LPL mRNA
      expression. In THP-1 cells treated with PPAR alpha and gamma ligands, enhanced
      nuclear protein binding to the peroxisome proliferator responsive element (PPRE)
      of the human LPL promoter was observed. Furthermore, in these cells, a decreased
      rate of decay of LPL mRNA was documented. Overall, these results demonstrate that
      PPAR alpha and gamma activators increase macrophage LPL secretion. Given the
      proatherogenic effect of vascular wall LPL, better understanding of the role of
      PPARs in the regulation of macrophage LPL expression could lead to the
      development of new approaches in the prevention and treatment of atherosclerosis.

PMID- 12208476
TI  - Platelet collagen receptor GPIa (C807T/HPA-5) haplotype is not associated with an
      increased risk of fatal coronary events in middle-aged men.
AB  - Platelet GPIa/IIa receptors play key roles in the adhesion of platelets to
      collagen during the formation of coronary thrombosis. The C807T and HPA-5
      polymorphisms of the gene for GPIa define three distinct alleles of GPIa which
      are associated with the surface expression of the protein in an allele-dependent
      fashion. Significance of these polymorphisms in victims of sudden cardiac death
      (SCD) was studied in Helsinki Sudden Death Study (HSDS) comprising 700 autopsied
      middle-aged Caucasian Finnish men with 288 SCD victims and 84 men with fatal
      acute myocardial infarction (AMI). The high-expression A1 allele was found in
      36.6% of control men as opposed to 38.0% of all SCD victims and 36.9% of men with
      fatal AMI (P>0.4). The high-expression A1A1 genotype was found in 11.9% of men
      with fatal AMI and 10.0% of controls as opposed to the low-expression A2A2
      genotype which was found in 29.8% of men with fatal AMI and in 31.2% of controls
      (OR 1.2, P>0.3). Age group (under/over 55) had no effect on the results. Our
      results do not support an effect of the GPIa haplotype on fatal coronary events
      among middle-aged men.

PMID- 12208477
TI  - Effect of gender on phenotypic expression of the S447X mutation in LPL: the
      Copenhagen City Heart Study.
AB  - The G188E, D9N, and N291S mutations in LPL increase TG, reduce HDL cholesterol,
      and increase risk of ischemic heart disease. The common S447X mutation may have
      opposite effects. We genotyped 8451 women and men from the Danish general
      population, and 854 women and men with ischemic heart disease. Participants
      carrying G188E, D9N, or N291S were excluded. Compared with non-carriers, female
      heterozygotes and homozygotes presented with a 0.11 and 0.18 mmol/l decrease in
      plasma TG (P=0.001 and P=0.37) and a 0.07 and 0.03 mmol/l increase in HDL
      cholesterol (P=0.001 and P=0.99). Male heterozygotes and homozygotes presented
      with a 0.20 and 0.41 mmol decrease in plasma TG (P<0.001 and P=0.06), which was
      twice that in women, and a 0.05 and 0.17 mmol/l increase in plasma HDL
      cholesterol (P=0.02 and P=0.04), respectively. In meta-analyses by gender, the
      S447X mutation was associated with a significant l7% reduction in risk of
      ischemic heart disease in men (OR=0.83; P=0.01), whereas risk was unaffected in
      women (OR=0.97; P=0.98). The S447X mutation is associated with anti-atherogenic
      effects on TG and HDL cholesterol in both genders, and with a moderate protective
      effect on risk of ischemic heart disease in men.

PMID- 12208478
TI  - The apolipoprotein B R3500Q gene mutation in Spanish subjects with a clinical
      diagnosis of familial hypercholesterolemia.
AB  - Familial hypercholesterolemia (FH) and familial defective apolipoprotein B-100
      (FDB) are autosomal codominant diseases characterized by elevated LDL cholesterol
      levels and premature coronary artery disease. Mutations of the LDL-receptor and
      apolipoprotein B genes, which affect the binding domains of their protein
      products, are the causal defects. Securing the diagnosis of these conditions by
      molecular assays is important because it mandates early intervention for coronary
      risk reduction. DNA screening for apolipoprotein B R3500Q gene mutation was
      performed in 913 unrelated Spanish individuals with a clinical diagnosis of FH
      using a modified polymerase chain reaction protocol and restriction enzyme
      genotyping. Thirteen FDB heterozygotes were identified (frequency of 1.4% in
      subjects with a clinical diagnosis of FH). The prevalence of hypercholesterolemic
      subjects with FDB in the general Spanish population was estimated to be as low as
      2.8 x 10(-5) (95% CI, -3.1 x 10(-4) to 3.7 x 10(-4)). The ancestors of 11 out of
      13 FDB carriers were from Galicia, a region of Celtic ancestry in Northwestern
      Spain. As the series included 100 unrelated subjects of Galician ancestry, FDB
      appears to be an important genetic cause of hypercholesterolemia in this region.
      All the R3500Q mutations were found on the same allele, assigned to haplotype
      XbaI-/MspI+/EcoRI-/3HVR48, suggesting that the mutant alleles are identical by
      descent in people from Spain, as observed in other Caucasian populations. In
      conclusion, the R3500Q mutation of the apolipoprotein B gene, a common cause of
      FH in central Europe, is infrequent in the general Spanish population, but it is
      common in Galicia.

PMID- 12208479
TI  - The effects of lovastatin and simvastatin on the diurnal periodicity of plasma
      mevalonate concentrations in patients with heterozygous familial
      hypercholesterolemia.
AB  - Animal and human studies have shown that the biosynthesis of cholesterol exhibits
      diurnal periodicity with nocturnal increases in the level of cholesterol
      precursors. Dietary cholesterol, which increases the intracellular pool of
      cholesterol and plasma cholesterol levels, has been shown to blunt the nocturnal
      increases in cholesterol biosynthesis. Patients with heterozygous familial
      hypercholesterolemia (FH) have very high levels of plasma low-density lipoprotein
      cholesterol (LDL) due to their reduced ability to metabolize LDL particles. The
      present studies were carried out to determine whether diurnal variations in
      cholesterol synthesis occur in FH patients and to test the effects of 3-hydroxy-3
      methyl glutaryl CoA (HMG CoA) reductase inhibitors on the diurnal cycle of
      cholesterol biosynthesis in these patients. Diurnal rates of cholesterol
      synthesis were assessed by measuring the plasma concentrations of mevalonate, an
      intermediate in the pathway of cholesterol biosynthesis. Female FH patients
      exhibited a diurnal pattern in plasma mevalonate levels similar to that
      previously reported in controls with peak values occurring at night. Treatment
      with lovastatin and simvastatin (40 mg b.i.d.) significantly reduced 24-h mean
      plasma mevalonate levels from baseline values. Administration of lovastatin in
      the evening reduced the nocturnal increases in mevalonate levels, and the
      administration of simvastatin completely abolished the nighttime rise. These
      results demonstrate that inhibition of cholesterol biosynthesis by lovastatin and
      simvastatin modifies the normal diurnal rhythm of cholesterol biosynthesis in
      female FH patients.

PMID- 12208480
TI  - Effect of alcohol consumption on endothelial function in men with coronary artery
      disease.
AB  - An inverse relationship between moderate alcohol consumption and coronary artery
      disease (CAD) has been observed in several epidemiologic studies. Whether
      improvement of endothelial function is involved in this beneficial effect is
      unknown. We investigated endothelial function of the brachial artery in 108 men
      with CAD, 54 of whom consumed alcohol on at least 1 day per week. Brachial artery
      diameter responses to hyperemic flow (FMD) and to administration of nitroglycerin
      (NTG) spray were measured using high- resolution ultrasonography. Coronary risk
      factors and hyperuricemia were present more frequently among drinkers, who also
      had higher concentrations of triglyceride and apolipoproteins C2, C3, and E. FMD
      was greater in drinkers (P<0.0001), while NTG-induced dilation was not. Multiple
      regression analysis showed alcohol consumption to be one of the factors favorably
      influencing FMD. These findings suggest that alcohol consumption may improve
      endothelial function in men with CAD.

PMID- 12208481
TI  - Association of the factor XII 46C>T polymorphism with risk of coronary heart
      disease (CHD) in the WOSCOPS study.
AB  - AIM: To evaluate the contribution of the 46C>T polymorphism of the Factor XII
      (FXII) gene to risk for coronary heart disease (CHD) in the West of Scotland
      Coronary Prevention Study (WOSCOPS) of men with high cholesterol. BACKGROUND:
      WOSCOPS is a primary prevention trial that demonstrated the effectiveness of
      pravastatin in reducing morbidity and mortality from CHD. FXII is a protein of
      the contact system that plays a key role in both coagulation and fibrinolysis.
      Elevated activated FXII (FXIIa) levels have been previously associated with CHD.
      Plasma FXIIa levels are strongly determined by a 46C>T polymorphism in the FXII
      gene. RESULTS: 441 CHD cases and 990 controls were genotyped. The frequency of TT
      homozygotes was 8.3% in controls and 11.8% in cases (P=0.04). When compared with
      the CC+CT group (after adjustment for age, blood pressure, BMI, fibrinogen and
      lipid levels) the TT genotype was an independent risk factor for CHD (OR 1.48 95%
      CI 1.01-2.17), an effect that was only significant in the pravastatin group (OR
      1.95 95% CI 1.09-3.47) and not in the placebo group (OR 1.20, 95%CI 0.72-2.02).
      Compared with risk in the placebo group as a whole (reference group), and after
      adjustment for other risk factors, men with the CC or CT genotype, but not the TT
      genotype showed a significant benefit from pravastatin treatment (OR,
      respectively, 0.61 (0.46-0.81) and 0.56 (0.40-0.79) compared with 1.10 (0.64
      1.96). In a subgroup of these men, subjects with the TT genotype had, as
      expected, baseline levels of FXIIa that were 50% lower than those with the CC
      genotype, with CT subjects having intermediate levels (P<0.001 by Kruskal-Wallis
      test). CONCLUSIONS: The TT genotype of the FXII 46C>T polymorphism is associated
      with a high risk of CHD in men with high cholesterol. We hypothesise that reduced
      fibrinolysis in these men, as a consequence of lower plasma FXIIa, may be the
      mechanism leading to higher risk, and that pravastatin treatment may enhance this
      effect.

PMID- 12208482
TI  - Association of factor VII levels with inflammatory parameters in
      hypercholesterolemic patients.
AB  - Inflammatory markers have been demonstrated to be associated with increased risk
      of cardiovascular events. In this setting, C-reactive protein (CRP) was shown to
      add predictive value to cholesterol levels. We investigated hypercholesterolemic
      patients and related their inflammatory variables and their coagulation state
      focusing on factor VII, a coagulation protein which plays an established role in
      thrombogenesis. We examined the relationship between factor VII clotting activity
      (FVIIc), FVII antigen (FVIIAg) and activated FVII (FVIIa) levels against CRP,
      interleukin-6 soluble receptor (IL-6sR), P-selectin, soluble intercellular
      adhesion molecule-1 (ICAM-1) and transforming growth factor-beta(1) (TGF
      beta(1)), in fifty-eight hypercholesterolemic subjects. Patients were subjected
      to 6-8 weeks of lipid lowering treatment with diet or diet plus pravastatin (40
      mg/day). Univariate analysis showed that FVII levels were positively associated
      with CRP (FVIIAg: r=0.56, P<0.0001; FVIIc: r=0.57, P<0.0001; FVIIa: r=0.39,
      P<0.001) and IL-6sR (FVIIAg: r=0.59, P<0.0001; FVIIc: r=0.52, P<0.0001; FVIIa:
      r=0.47; P<0.001). CRP was still correlated, at the baseline, with FVIIAg and
      FVIIc levels after multiple stepwise regression analysis (FVIIAg: P<0.0001;
      FVIIc: P<0.0001, respectively) and with FVIIAg at the end of lipid lowering
      treatment (P<0.0001). Our data indicate that the FVII level is independently
      associated with inflammatory variables and suggest their pathophysiological link
      in hypercholesterolemic patients.

PMID- 12208483
TI  - Homocysteine is the only plasma thiol associated with carotid artery remodeling.
AB  - Several authors have reported that moderate hyperhomocysteinemia is related to
      asymptomatic carotid arterial wall remodeling, but few data are available on
      other thiol compounds with potential vascular toxicity. We, therefore,
      investigated the relationships between major plasma thiol compounds
      (homocysteine, cysteine and glutathione) and the structural phenotype of the
      common carotid artery in a cohort of 123 subjects with no evidence of
      cardiovascular disease. Fasting levels of thiol compounds were measured by high
      performance liquid chromatography, and arterial geometry was evaluated using high
      resolution echotracking devices. In univariate regression analysis, plasma
      homocysteine and plasma cysteine concentrations were positively associated with
      carotid artery internal diameter (P=0.0001 and 0.002, respectively) and intima
      media thickness (P=0.003 and 0.004), but the plasma glutathione concentration was
      not. In multivariate analysis, plasma homocysteine was independently and
      positively associated with carotid artery internal diameter (P<0.005) and intima
      media thickness (P<0.05), but plasma cysteine was not. These data suggest that
      homocysteine is the only plasma thiol compound that may be considered as a risk
      factor for preclinical cardiovascular disease.

PMID- 12208484
TI  - The angiotensin-converting-enzyme insertion/deletion polymorphism is not a risk
      factor for peripheral arterial disease.
AB  - BACKGROUND: An insertion/deletion (I/D) polymorphism of the gene for angiotensin
      converting-enzyme (ACE) is associated with ACE plasma levels and activity.
      Conflicting results have been reported about the relevance of this polymorphism
      for atherosclerotic vascular disease. The aim of the present study was to analyze
      the role of this polymorphism for peripheral arterial disease (PAD). METHODS: The
      study was designed as a case-control study including 522 patients with documented
      PAD and 522 sex- and age-matched controls. ACE genotype was determined by size
      analysis of polymerase chain reaction products. RESULTS: ACE genotype frequencies
      were similar between patients (II: 23.4%; ID: 44.8%; DD: 31.8%) and controls (II:
      23.8%; ID: 48.3%; DD: 27.9%, P=0.37). The adjusted odds ratio of carriers of the
      DD genotype for PAD was 1.29 (95% confidence interval 0.95-1.75). The
      polymorphism was furthermore not associated with age at onset of PAD (P=0.56),
      Fontaine stage of the disease (P=0.68) or ankle/brachial index of patients
      (P=0.86). CONCLUSION: The ACE I/D polymorphism is not a significant risk factor
      for PAD.

PMID- 12208485
TI  - Relationship of serum ferritin with cardiovascular risk factors and inflammation
      in young men and women.
AB  - Elevated ferritin levels have been reported as a risk factor for coronary heart
      disease in Finnish and Italian studies. Studies in other populations have found
      no association between ferritin and cardiovascular disease raising the
      possibility of confounding with other cardiovascular risk factors. We determined
      ferritin levels, metabolic cardiovascular risk factors, C-reactive protein (CRP),
      anthropometric measurements and blood pressure in 815 men and women aged 26
      years. In women serum ferritin correlated with CRP, waist measurement, body mass
      index (BMI), and triglycerides. In multiple regression analysis CRP alone was
      independently associated with serum ferritin. Serum ferritin in men correlated
      with waist measurement, BMI, triglycerides and high-density lipoprotein (HDL)
      cholesterol. After adjustment for the other variables, waist measurement was the
      only independent predictor of ferritin. Ferritin levels in young men and women
      are associated with obesity and serum triglycerides, HDL cholesterol in men and
      inflammation in women. Confounding may contribute to reports of associations
      between ferritin and cardiovascular disease.

PMID- 12208486
TI  - Administration of orlistat in a patient with familial hyperchylomicronemia.

PMID- 12208487
TI  - Effects of various fibrates on serum alkaline phosphatase activity.

PMID- 12208488
TI  - Left prefrontal-repetitive transcranial magnetic stimulation (rTMS) and regional
      cerebral glucose metabolism in normal volunteers.
AB  - Repetitive transcranial magnetic stimulation (rTMS) holds promise as a probe into
      the pathophysiology and possible treatment of neuropsychiatric disorders. To
      explore its regional effects, we combined rTMS with positron emission tomography
      (PET). Fourteen healthy volunteers participated in a baseline 18
      fluorodeoxyglucose (FDG) PET scan. During a second FDG infusion on the same day,
      seven subjects received 30 min of 1 Hz rTMS at 80% of motor threshold to left
      prefrontal cortex, and seven other subjects received sham rTMS under identical
      conditions. Global and normalized regional cerebral glucose metabolic rates
      (rCMRglu) from the active and sham conditions were compared to baseline and then
      to each other. Sham, but not active 1 Hz rTMS, was associated with significantly
      increased global CMRglu. Compared to baseline, active rTMS induced normalized
      decreases in rCMRglu in right prefrontal cortex, bilateral anterior cingulate,
      basal ganglia (L>R), hypothalamus, midbrain, and cerebellum. Increases in rCMRglu
      were seen in bilateral posterior temporal and occipital cortices. Sham rTMS
      compared to baseline resulted in isolated normalized decreases in rCMRglu in left
      dorsal anterior cingulate and left basal ganglia, and increases in posterior
      association and occiptal regions. Differences between the 1 Hz active versus sham
      changes from baseline revealed that active rTMS induced relative decrements in
      rCMRglu in the left superior frontal gyrus and increases in the cuneus (L>R). One
      Hertz rTMS at 80% motor threshold over the left prefrontal cortex in healthy
      subjects compared to sham rTMS in another group (each compared to baseline)
      induced an area of decreased normalized left prefrontal rCMRglu not directly
      under the stimulation site, as well as increases in occipital cortex. While these
      results are in the predicted direction, further studies using other designs and
      higher intensities and frequencies of rTMS are indicated to better describe the
      local and distant changes induced by rTMS.

PMID- 12208489
TI  - Regional cerebral blood flow and neuropsychological functioning in early and late
      onset alcoholism.
AB  - The aim of the study was to compare late and early onset alcoholism with regard
      to regional cerebral blood flow (rCBF) and neuropsychological functioning. Ten
      late onset and 13 early onset male alcoholics were included in the study, the
      criterion being the age of onset for alcohol abuse. Six healthy male volunteers
      were included as a control group. Regional measures of cortical cerebral blood
      flow were assessed using Tc-99m-HMPAO single photon emission computed tomography
      (SPECT) after a detoxification period. When compared with the control group, the
      early onset group showed reduced relative perfusion in the left superior frontal
      region, while relative perfusion in the late onset group was deficient in both
      right and left superior frontal regions. Both groups of alcoholic patients also
      displayed impairment in frontal lobe functions and non-verbal memory. The results
      of this study indicate that early onset alcoholism is associated with
      hypoperfusion in the left superior frontal region while the late onset subtype is
      characterized by uniformly hypoperfused left and right superior frontal regions.
      Additionally, both groups of alcoholic patients exhibit an almost identical
      pattern of neuropsychological abnormalities mainly related to frontal lobe
      functions and non-verbal memory. Collectively these findings support previous
      evidence suggesting a key role of frontal lobe pathology in understanding the
      neurobiology of alcoholism.

PMID- 12208490
TI  - Investigation of a possible diencephalic pathology in schizophrenia.
AB  - Absence of the adhesio interthalamica (AI) in schizophrenic first episode
      patients is suggestive for another marker of early developmental neuropathologic
      changes. Moreover, findings suggest that schizophrenic patients without AI are
      characterised by more severe negative symptoms. The study aims to investigate the
      presence vs. absence of AI in relation to brain measurements and clinical
      features. Presence or absence of AI and volumetric brain measurements were
      assessed in 50 patients with schizophrenia and 50 matched controls. No
      differences in the incidence of AI were found between the groups. Patients
      without AI revealed a strong trend towards a larger third ventricle and
      significantly higher scores for negative symptoms. Interestingly, the subgroup of
      healthy controls without AI also had larger third ventricles. The absence of AI
      may represent another early developmental marker of cerebral malformation in a
      clinical subgroup of schizophrenic patients.

PMID- 12208491
TI  - Cerebral correlates of selective attention in schizophrenic patients with formal
      thought disorder: a controlled H2 15O-PET study.
AB  - There is a widespread belief that formal thought disorders may be associated with
      disturbed selective attention in schizophrenia. Two hypotheses are derived: (1)
      patients with slightly pronounced formal thought disorders should differ from
      those with severely expressed formal thought disorders in terms of selective
      attention; and (2) the cerebral correlates of selective attention should be
      organised differently in mildly versus severely thought-disordered patients. We
      compared 20 female schizophrenic patients, one-half with mild, one-half with
      obvious formal thought disorders, and 10 control subjects on a neuropsychological
      battery and a cognitive activation task for selective attention (Go/NoGo) for the
      assessment of rCBF using H2 15O-PET. While the first hypothesis has not been
      confirmed, we found that the cerebral regions activated by selective attention in
      the two patient groups showed completely differing organisations. Low degrees of
      formal thought disorders were associated with significant activations in frontal
      superior gyrus and ventral anterior thalamic nucleus whereas high degrees of
      formal thought disorders were accompanied by significant activations in fusiform
      gyrus and precuneus. We suggest that differing task-solving strategies are
      applied by both clinical subgroups to achieve comparable results on the selective
      attention paradigm.

PMID- 12208492
TI  - Temporal modulation of cerebral hemodynamics under prefrontal challenge in
      schizophrenia: a transcranial Doppler sonography study.
AB  - Transcranial Doppler sonography (TCD) is a non-invasive method to assess cerebral
      blood flow velocity (CBFV) and hence cerebral blood flow during cognitive
      activation. Major cognitive dysfunctions have been consistently reported in
      patients with schizophrenia, and important deficits have been observed with
      respect to prefrontal functions. However, prefrontal activation in schizophrenics
      has not been investigated with TCD despite its potential to examine short-term
      changes of cerebral blood flow. The Wisconsin Card Sorting Test (WCST) and the
      Tower of Hanoi puzzle were administered to 11 right-handed schizophrenics and 20
      healthy controls. The middle and anterior cerebral arteries were pairwise
      insonated. Schizophrenics showed decreased CBFV during the initial phase of both
      prefrontal functions and the steady-state phase of the Tower of Hanoi. In healthy
      controls, there was a succession of three significantly different phases of mean
      CBFV during the Tower of Hanoi, and there was no such modulation in
      schizophrenics. Immediately after category shift in the WCST, there was an
      increase of mean CBFV in healthy controls, but not in schizophrenics. In
      conclusion, transcranial Doppler sonography was able to detect differing specific
      alterations of CBFV during two prefrontal tasks in healthy controls and patients
      with schizophrenia. Importantly, the results of this study imply a degraded
      pattern of CBFV changes over time in schizophrenia during prefrontal activation.

PMID- 12208493
TI  - Why are sweet proteins sweet? Interaction of brazzein, monellin and thaumatin
      with the T1R2-T1R3 receptor.
AB  - Sweet tasting proteins interact with the same receptor that binds small molecular
      weight sweeteners, the T1R2-T1R3 G-protein coupled receptor, but the key groups
      on the protein surface responsible for the biological activity have not yet been
      identified. I propose that sweet proteins, contrary to small ligands, do not bind
      to the 'glutamate-like' pocket but stabilize the free form II of the T1R2-T1R3
      receptor by attachment to a secondary binding site. Docking of brazzein, monellin
      and thaumatin with a model of the T1R2-T1R3 sweet taste receptor shows that the
      most likely complexes can indeed stabilize the active form of the receptor.

PMID- 12208494
TI  - Towards a new T-fold protein?: the coproporphyrinogen III oxidase sequence
      matches many structural features from urate oxidase.
AB  - Urate oxidase (UOX) and coproporphyrinogen III oxidase (CPO) are two unusual
      oxidases as they accomplish their catalytic act with no co-factor nor metal ion.
      They both require molecular oxygen, and lead to hydrogen peroxide in addition to
      the product. UOX is composed of two contiguous Tunneling-fold domains and CPO
      appears to be also divided into two structurally equivalent domains. Moreover,
      each of these putative domains can be coherently aligned on UOX domains. Although
      their sequences are very distant, we therefore suggest that functional CPO dimer
      is built around a tunnel, with the substrate sitting above it, on the N- and C
      terminal side. This overall model is supported by mutation data and is coherent
      with the chemical events expected for substrate processing by CPO.

PMID- 12208495
TI  - Orexin signaling in recombinant neuron-like cells.
AB  - To assess the role of orexin receptor signaling in neuron-like cells, Neuro-2a
      murine neuroblastoma and PC12 human pheochromocytoma cells were stably
      transfected with human OX(1) or OX(2) receptors. Activation of both receptors
      strongly elevated cellular inositol phosphates and Ca(2+). A difference in the
      potency between orexin-A and -B was seen for OX(1), but not OX(2) receptors.
      Dependence of the orexin-mediated Ca(2+) response on extracellular Ca(2+) and the
      observed Ba(2+) influx indicate that in addition to phospholipase C, orexin
      receptors also may couple to similar non-voltage-gated Ca(2+) channels in
      neuronal cells as previously characterized in non-neuronal cells.

PMID- 12208496
TI  - Divergent role of ceramide generated by exogenous sphingomyelinases on NF-kappa B
      activation and apoptosis in human colon HT-29 cells.
AB  - This study examined the role of ceramide generated by exogenous sphingomyelinases
      (SMases) on transcription nuclear factor-kappa B (NF-kappa B) activation and
      apoptosis in human colon epithelial HT-29 cells. Exogenous neutral (N) and acidic
      (A) SMase activated NF-kappa B with different kinetics, accounting for the
      diverse pattern of DNA binding of NF-kappa B complexes activated by tumor
      necrosis factor-alpha (TNF). NSMase activated predominantly RelA/p52 and RelA/p50
      dimers within 30 min, while ASMase activated the p50/p50 homodimer by 20 h. The
      predominant activation of RelA-containing kappa B complexes by TNF or NSMase
      paralleled the induction of interleukin-8. HT-29 cells were sensitive to ASMase
      and TNF but resistant to NSMase. However, the apoptotic potential of NSMase was
      masked by NF-kappa B, as its prior inactivation sensitized HT-29 cells to NSMase.
      Thus, the generation of ceramide by exogenous SMases participates differentially
      in inflammation and apoptosis.

PMID- 12208497
TI  - Huperzine A attenuates apoptosis and mitochondria-dependent caspase-3 in rat
      cortical neurons.
AB  - The neuroprotection of huperzine A against apoptosis was investigated. In
      cultures of rat primary cortical neurons, neuronal apoptosis was induced by serum
      deprivation for 24 h, which was accompanied by enhanced caspase-3 activity and
      the release of cytochrome c into the cytosol from mitochondria. Pretreating the
      neurons for 2 h with huperzine A (0.1-10 microM) improved neuronal survival.
      Huperzine A at a concentration of 1 microM significantly attenuated apoptosis by
      inhibiting the mitochondria-caspase pathway directly and indirectly.

PMID- 12208498
TI  - Resistin expression and regulation in mouse pituitary.
AB  - Resistin, a new adipocytokine, is expressed in human, rat and mouse adipose
      tissue. Its putative role as a mediator of insulin resistance is controversial.
      We hypothesized that resistin, in common with leptin, has multiple roles in non
      adipose tissues. Using reverse transcription polymerase chain reaction (RT-PCR)
      we show that the resistin gene (Retn) is expressed in mouse brain (hypothalamus
      and cortex) and pituitary gland. Immunohistochemistry revealed resistin protein
      in the arcuate nucleus and pituitary gland. Semi-quantitative RT-PCR analysis
      indicated that Retn mRNA is developmentally regulated in the pituitary.
      Expression was lowest at birth, increased abruptly between postnatal days 14 and
      25 (four-fold; P<0.001), and declined thereafter. This peak in pituitary Retn
      mRNA was unaffected by early weaning but was abolished by neonatal treatment with
      monosodium glutamate, suggesting that the basal hypothalamus regulates pituitary
      Retn. Although the role(s) of endogenous resistin in mouse brain and pituitary
      remains to be determined, it may be distinct from its controversial involvement
      in insulin resistance. Our data suggest that local resistin expression could have
      functional implications during prepubertal maturation of the hypothalamic
      pituitary system.

PMID- 12208499
TI  - Mutagenic and functional analysis of the C-terminus of Saccharomyces cerevisiae
      Pho84 phosphate transporter.
AB  - A widely accepted mechanism for selective degradation of plasma membrane proteins
      is via ubiquitination and/or phosphorylation events. Such a regulated degradation
      has previously been suggested to rely on the presence of a specific SINNDAKSS
      sequence within the protein. Modification of a partly conserved SINNDAKSS-like
      sequence in the C-terminal tail of the Pho84 phosphate transporter, in
      combination with C-terminal fusion of green fluorescent protein or a MYC epitope,
      were used to evaluate the presence of this sequence and its role in the regulated
      degradation. The functional Pho84 mutants in which this SINNDAKSS-like sequence
      was altered or truncated were subjected to degradation like that of the wild
      type, suggesting that degradation of the Pho84 protein is regulated by factors
      other than properties of this sequence.

PMID- 12208500
TI  - Sustained activation of AMP-activated protein kinase induces c-Jun N-terminal
      kinase activation and apoptosis in liver cells.
AB  - The aim of this work was to study the effect of a sustained activation of AMP
      activated protein kinase (AMPK) on liver cell survival. AMPK activation was
      achieved by incubating FTO2B cells with AICA-riboside, which is transformed into
      ZMP, an AMP analogue, or by adenoviral transfection of hepatocytes with a
      constitutively active form of AMPK. Prolonged AMPK activation triggered apoptosis
      and activated c-Jun N-terminal kinase (JNK) and caspase-3. Experiments with
      iodotubercidin, dicoumarol and z-VAD-fmk, which inhibited AMPK, JNK and caspase
      activation, respectively, supported the notion that prolonged AMPK activation in
      liver cells induces apoptosis through an activation pathway that involves JNK and
      caspase-3.

PMID- 12208501
TI  - Conversion of the dimeric D-amino acid oxidase from Rhodotorula gracilis to a
      monomeric form. A rational mutagenesis approach.
AB  - The relevance of the dimeric state for the structure/function relationships of
      Rhodotorula gracilis D-amino acid oxidase (RgDAAO) holoenzyme has been
      investigated by rational mutagenesis. Deletion of 14 amino acids in a surface
      loop (connecting beta-strands 12 and 13) transforms RgDAAO from a dimeric protein
      into a stable monomer. The mutant enzyme is still catalytically competent and
      retains its binding with the FAD coenzyme. Dimerization has been used by this
      flavoenzyme in evolution to achieve maximal activity, a tighter interaction
      between the protein moiety and the coenzyme, and higher thermal stability.

PMID- 12208502
TI  - A desaturase-like protein from white spruce is a Delta(9) desaturase.
AB  - Gymnospermae seed lipids are characterized by a high degree of desaturation, most
      having a Delta(9) double bond. By degenerate polymerase chain reaction (PCR) we
      have isolated a white spruce (Picea glauca) cDNA clone that encodes an amino acid
      sequence sharing a high degree of homology with other putative plant acyl
      coenzyme A (CoA) Des9 desaturases. Both in vivo and in vitro expression studies
      in a Delta(9) desaturase-deficient yeast strain demonstrated the desaturation
      functionality of the white spruce clone, and gas chromatography-mass spectrometry
      (GC-MS) analyses confirmed the regioselectivity of the encoded enzyme. This is
      the first report of the functional characterization of a plant membrane-bound
      acyl-CoA-like protein Delta(9) desaturase by heterologous expression in yeast.

PMID- 12208503
TI  - A tormentor in the quest for plant p53-like proteins.
AB  - Over the past few years the presence of p53-like proteins in plants was
      frequently reported, by using the monoclonal antibody Pab240. By means of protein
      purification and screening a cDNA library, a Pab240 cross-reacting protein and a
      cDNA clone were isolated from barley. Peptide- and DNA-sequence analysis
      identified one and the same protein: 2-oxoglutarate dehydrogenase. Sequence
      analysis of 2-oxoglutarate dehydrogenase revealed that the protein contains a
      perfect Pab240 epitope. In barley, the 110 kDa oxoglutarate dehydrogenase was
      degraded during isolation to a 53 kDa Pab240 cross-reacting polypeptide, thereby
      mimicking curiously p53-like properties.

PMID- 12208504
TI  - The micro domain responsible for ligand-binding of guanylyl cyclase C.
AB  - Guanylyl cyclase C (GC-C), a member of membrane-bound guanylyl cyclases, is a
      receptor protein for guanylin and uroguanylin. The binding of a ligand to the
      extracellular domain of GC-C (ECD(GC-C)) triggers signal transduction, resulting
      in the regulation of intestinal fluids and electrolytes. A previous study
      proposed that a ligand-binding site on GC-C is localized near the transmembrane
      region. To further investigate the mechanism by which GC-C is activated, the C
      terminal polypeptide (Met341-Gln407) of ECD(GC-C) (the micro domain), which
      includes the ligand-binding site, was over-expressed in Escherichia coli and its
      ligand-binding ability was examined. The micro domain showed ligand-binding
      activity (IC(50)=1 x 10(-8) M). This result clearly indicates that a ligand
      binding site is located in close proximity to the membrane-bound region, and that
      the micro domain is capable of independently binding the ligand, without
      assistance from other domains. The use of this micro binding domain in the study
      of interactions between GC-C and ligands could be a useful tool and could lead to
      a better understanding of GC-C signal transduction.

PMID- 12208505
TI  - Photoaffinity labeling of the uncoupling protein UCP1 with retinoic acid:
      ubiquinone favors binding.
AB  - Retinoic acid is a potent activator of the uncoupling protein-1 (UCP1) both at
      the gene and mitochondrial level. Irradiation with ultraviolet light can be used
      to directly photolabel proteins with retinoic acid. The procedure has been
      applied to investigate its interaction with UCP1 isolated from brown adipose
      tissue mitochondria. All-trans-retinoic acid binds to UCP1 with high affinity and
      the labeling is only partially protected by guanosine diphosphate. Ubiquinone
      (UQ) has been described to be an obligatory cofactor for uncoupling protein
      function and we demonstrate that it greatly increases the affinity of UCP1 for
      retinoic acid. Data support the notion of a direct interaction between UQ and
      retinoic acid.

PMID- 12208506
TI  - Domain structure and ATP-induced conformational changes in Escherichia coli
      protease Lon revealed by limited proteolysis and autolysis.
AB  - Escherichia coli protease Lon (La) is an adenosine triphosphate (ATP)-regulated
      homo-oligomeric proteolytic complex responsible for the recognition and selective
      degradation of abnormal and unstable proteins. Each subunit of the protease Lon
      appears to consist of three functional domains: the C-terminal proteolytic
      containing a serine active site, the central displaying the ATPase activity, and
      the N-terminal with still obscure function. We have used limited proteolysis to
      probe the domain structure and nucleotide-induced conformational changes in the
      enzyme. Limited proteolysis of the native protease Lon generated a low number of
      stable fragments roughly corresponding to its functional domains. Conformational
      changes in the wild-type enzyme and its mutant forms in the presence or absence
      of adenine and guanine nucleotides were investigated by limited proteolysis. The
      nucleotide character was shown to play a key role for susceptibility of the
      protease Lon to limited proteolysis, in particular, for resistance of the ATPase
      functional domain. ATP and adenosine diphosphate displayed a protective effect of
      the ATPase domain of the enzyme. We suggest that these nucleotides induce
      conformational changes of the enzyme, transforming the ATPase domain from the
      most vulnerable part of the molecule into a spatially inaccessible one. Both
      limited proteolysis and autolysis demonstrate that the most stable part of the
      protease Lon molecule is its N-terminal region. Obvious resistance of the
      protease Lon C-terminus to proteolysis indicates that this region of the enzyme
      molecule including its substrate-binding and proteolytic domains has a well
      folded structure.

PMID- 12208507
TI  - Ccz1p/Aut11p/Cvt16p is essential for autophagy and the cvt pathway.
AB  - In a reverse genetics screen, we here identify Ccz1p as an essential component of
      the cvt pathway and autophagy. Ccz1p is identical with the so far unknown Cvt16p.
      GFP-Aut7p, a specific cargo of autophagosomes, accumulates in ccz1 Delta cells at
      punctate, vesicular structures in the cytosol, suggesting a block in the
      autophagic pathway prior to vacuolar fusion of autophagosomes. Proteinase
      protection experiments using hypotonically lysed ccz1 Delta spheroplasts
      demonstrate that proaminopeptidase I, another specific cargo of autophagy and the
      cvt pathway, is trapped inside membrane-enclosed vesicles. Taken together our
      findings are compatible with a function of Ccz1p in vacuolar fusion of cvt
      vesicles and autophagosomes.

PMID- 12208508
TI  - Characterization and thermodynamic properties of quadruplex/duplex competition.
AB  - Structural characteristics and thermodynamic properties of dG(3)(T(2)AG(3))(3),
      d(C(3)TA(2))(3)C(3) and dG(3)(T(2)AG(3))(3)/d(C(3)TA(2))(3)C(3) were intensively
      investigated. It was indicated that metal ions greatly affected the conformation
      and stability of the G-quadruplex. A competition of a structure transition among
      the G-quadruplex, I-motif, and the duplex was confirmed to be dependent on both
      cation species and pH values. The structural competitive mechanism is discussed
      for the first time. This study shows an intriguing potential in modulating DNA
      structures in vivo, which is of great importance in drug design and cancer
      chemotherapy.

PMID- 12208509
TI  - Cyclin E and cyclin A are likely targets of Src for PDGF-induced DNA synthesis in
      fibroblasts.
AB  - How tyrosine kinases of the Src family regulate platelet-derived growth factor
      (PDGF)-induced DNA synthesis remains elusive. Here we show that the E1A antigen
      of adenovirus 5 overrides the G1 block elicited by the kinase-inactive mutant
      SrcK(-). This was dependent upon the CR2 region of E1A that upregulated cyclin E
      and cyclin A and inactivated the pocket protein pRb. E1A rescue was independent
      of pRb. Expression of SrcK(-) in fibroblasts prevented PDGF-induced expression of
      cyclins E and A. This effect was overcome by E1A. Constitutive expression of
      cyclins E and A, but not D1, restored mitogenesis that was inhibited by SrcK(-).
      We conclude that both cyclin E and cyclin A are likely targets of Src mediating
      PDGF-induced DNA synthesis.

PMID- 12208510
TI  - Calnexin Delta 185-520 partially reverses the misprocessing of the Delta F508
      cystic fibrosis transmembrane conductance regulator.
AB  - Abnormal retention of Delta F508 CFTR (cystic fibrosis transmembrane conductance
      regulator) in the endoplasmic reticulum is a major cause of cystic fibrosis (CF).
      We show that calnexin Delta 185-520 but not calnexin can partially reverse the
      mislocalization of Delta F508 CFTR. This 256-amino acid protein has neither the
      transmembrane domain nor the P domain of calnexin. Calnexin Delta 185-520
      interacted with CFTR directly, and was secreted into the extracellular
      compartment over time. Forty-eight hours after transfection into CHO cells,
      calnexin Delta 185-520 increased the conversion of immature Delta F508 CFTR into
      mature Delta F508 CFTR. In immortalized human CF cell lines expressing Delta F508
      CFTR, a halide efflux assay showed that calnexin Delta 185-520 partially restored
      CFTR function. These data indicate that calnexin Delta 185-520 may give a clue to
      develop the therapeutic way of cystic fibrosis with Delta F508 CFTR.

PMID- 12208511
TI  - Only the soluble form of the scavenger receptor CD163 acts inhibitory on phorbol
      ester-activated T-lymphocytes, whereas membrane-bound protein has no effect.
AB  - The extracellular moiety of the hemoglobin/haptoglobin scavenger receptor CD163
      (RM3/1 antigen) can be shed from monocytes and is a normal plasma component. We
      found that in a dose-dependent manner soluble CD163 induces a decrease in CD69
      expression, a reduced [(3)H]thymidine uptake and a down-regulated matrix
      metalloproteinase-9 RNA expression in phorbol myristate acetate-stimulated T
      cells. Co-culturing T-cells on transgenic fibroblasts, expressing membrane-bound
      CD163, yielded no differences compared to culture on non-transfected cells. We
      conclude that CD163 has at least two distinct functions: the clearance of
      hemoglobin in its cell-bound form and participation in anti-inflammation as a
      soluble factor, exhibiting cytokine-like functions.

PMID- 12208512
TI  - Monte Carlo simulations of voltage-driven translocation of a signal sequence.
AB  - Transmembrane potentials play important but poorly understood roles in many
      biological processes, including signal sequence-mediated protein translocation
      across bacterial membranes. In this study we applied Monte Carlo techniques to
      simulate the way the potential acts on a signal sequence. The simulations
      demonstrate that in the absence of a potential the signal sequence prefers
      insertion in both helical hairpin and transmembrane alpha-helical conformations.
      However, in the presence of a potential only the transmembrane alpha-helical
      conformation is the state of lowest energy for the signal sequence. From these
      results it is concluded that the membrane potential stabilizes the transmembrane
      orientation of a signal sequence, explaining the membrane potential dependence of
      preprotein translocation.

PMID- 12208513
TI  - Proteasome inhibitors stimulate activator protein-1 pathway via reactive oxygen
      species production.
AB  - In this report we explored the effects of proteasome inhibitors (MG132, aLLN,
      lactacystin and MG262) on interleukin-8 (IL-8) induction. In HEK293 cells,
      proteasome inhibitors could concentration-dependently increase IL-8 promoter and
      activator protein-1 (AP-1) activities, but inhibited nuclear factor (NF)-kappa B
      activation induced by cytokines. The stimulating effects on IL-8 promoter and AP
      1 were reduced by N-acetylcysteine, glutathione, diphenyleneiodonium, rotenone
      and antimycin A. Fluorescent analysis using 2',7'-dichlorodihydrofluorescin
      diacetate further confirmed the abilities of proteasome inhibitors to induce
      reactive oxygen species (ROS) production. These results suggest that ROS
      production by proteasome inhibitors leads to AP-1 activation, which in the
      absence of NF-kappa B activation still transactivates IL-8 gene expression.

PMID- 12208514
TI  - Intracellular redox regulation by a cystine derivative suppresses UV-induced NF
      kappa B activation.
AB  - Nuclear factor (NF)-kappa B pathways are influenced by the intracellular
      reduction-oxidation (redox) balance. While NF-kappa B is activated through
      inhibitor (I)-kappa B degradation by oxidative stress, its DNA binding is
      accelerated in the reduced state. We found that N,N'-diacetyl-L-cystine
      dimethylester (DACDM) suppressed the UVB-induced NF-kappa B binding activity at a
      much lower concentration (50-100 microM) than N-acetyl-L-cysteine (NAC, 10-30
      mM). While NAC suppressed the I-kappa B degradation but not the DNA binding,
      DACDM prevented the activated NF-kappa B from binding DNA, without influencing
      the I-kappa B degradation. These properties of DACDM make it possible to
      effectively regulate the intracellular redox balance.

PMID- 12208515
TI  - Arginine metabolism in Trypanosoma cruzi is coupled to parasite stage and
      replication.
AB  - L-Arginine plays an essential role in the energetic metabolism of Trypanosoma
      cruzi. In this work we propose a relationship between L-arginine uptake, arginine
      kinase activity and the parasite replication ability. In epimastigote cultures L
      arginine uptake decreases continuously accompanying a cell replication rate
      reduction. The use of conditioned or fresh medium mimics uptake variations.
      Interestingly, in non-replicative trypomastigote cells, L-arginine uptake was
      undetectable. The association between L-arginine uptake and cell replication was
      demonstrated using the antimitotic agent hydroxyurea. Arginine kinase, the enzyme
      responsible for phosphoarginine and ATP synthesis, also shows a differential
      activity in epimastigote and trypomastigote parasite stages.

PMID- 12208516
TI  - Restricted feeding induces daily expression of clock genes and Pai-1 mRNA in the
      heart of Clock mutant mice.
AB  - Plasminogen activator inhibitor-1 (PAI-1) is a key factor of fibrinolytic
      activity. The activity and mRNA abundance show a daily rhythm. To elucidate the
      mechanism of daily Pai-1 gene expression, the expression of Pai-1 and several
      clock genes was examined in the heart of homozygous Clock mutant (Clock/Clock)
      mice. Damping of the daily oscillation of Pai-1 gene expression in Clock/Clock
      mice was accompanied with damped or attenuated oscillations of mPer1, mPer2,
      mBmal1, and mNpas2 mRNA. Daily restricted feeding induced a daily mRNA rhythm of
      all clock genes and Pai-1 mRNA in Clock/Clock mice as well as wild-type mice. The
      peaks of clock genes and Pai-1 mRNA were phase-advanced in the heart of both
      genotypes after 6 days of restricted feeding. The present results demonstrate
      that daily Pai-1 gene expression depends on clock gene expression in the heart
      and that a functional Clock gene is not required for restricted feeding-induced
      resetting of the peripheral clock.

PMID- 12208517
TI  - Preimplantation-embryo-specific cell cycle regulation is attributed to the low
      expression level of retinoblastoma protein.
AB  - It is known that a characteristic of the mammalian preimplantation-embryo
      specific cell cycle is the substantially shortened G1-phase, although the
      regulation mechanisms of the unique cell cycle remain unclear. In the present
      study, we first examined the presence of retinoblastoma (RB) tumor suppressor
      gene product throughout mouse preimplantation embryo development and found that
      the RB expression was down-regulated between the four-cell and morula stages.
      Furthermore, the overexpression of RB protein in the mouse embryos during this
      phase inhibited their development significantly. These results suggest that the
      absence of RB protein contributes to the preimplantation-embryo-specific cell
      cycle.

PMID- 12208518
TI  - MIZIP, a highly conserved, vertebrate specific melanin-concentrating hormone
      receptor 1 interacting zinc-finger protein.
AB  - Using the yeast-two-hybrid system a novel protein was identified from human brain
      that interacts with the C-terminus of melanin-concentrating hormone receptor 1
      (MCH-R1). This protein, characterized by a Myeloid translocation protein 8,
      Nervy, DEAF1 proteins (MYND) zinc-finger domain, is termed MCH-R1-interacting
      zinc-finger protein, MIZIP. It is fully conserved in man, rat, mouse and highly
      conserved in Xenopus and zebrafish, but not detectable in invertebrates. MIZIP
      gene organization in human (six exons on chromosome 9q34.3) and mouse is highly
      conserved, yet in rodents an additional exon is generated giving rise to
      alternatively spliced mRNAs. MIZIP is expressed in brain, testis and stomach,
      where expression of MCH and MCH-R1 was previously reported. MIZIP interaction
      with MCH-R1 was verified by overlay and pull-down assays as well as by co
      transfection experiments in human embryonic kidney-293 cells. MIZIP is
      cytoplasmically localized but gets recruited to the plasma membrane when cells
      are co-transfected with MCH-R1 supporting the notion that MIZIP is involved in
      the function of MCH-R1.

PMID- 12208519
TI  - Important amino acid properties for determining the transition state structures
      of two-state protein mutants.
AB  - Understanding the mechanism in the folding pathways of proteins is an important
      problem in molecular biology. The Phi-value analysis provides insight into the
      transition state structures during protein folding. In this work, we have
      analyzed the relationship between the observed Phi values upon mutations in two
      state proteins (FK506 binding protein, chymotrypsin inhibitor and src SH3 domain)
      and the changes in 48 various physico-chemical, energetic and conformational
      properties. We found that the classification of mutations based on solvent
      accessibility improved the correlation significantly. The relationship between
      conformational properties and Phi values determines the presence/absence of
      secondary structures in the transition state. In buried mutations, the physical
      properties volume, shape and flexibility, and the thermodynamic properties
      enthalpy, entropy and free-energy change have significant correlation with Phi.
      The short and medium-range non-bonded energy in partially buried mutations and
      average long-range contacts in exposed mutations showed a strong correlation with
      Phi values. Multiple regression analysis incorporating combinations of three
      properties from among all possible combinations of the 48 properties increased
      the correlation coefficient up to 0.99, by an average rise of 20% for all the
      data sets. Information about local sequence and structure is more important in
      surface mutations than those in buried mutations for explaining the transition
      state structures of two-state proteins. Further, the implications of our results
      for understanding the process of protein folding have been discussed.

PMID- 12208520
TI  - Ceramide generated by acidic sphingomyelinase contributes to tumor necrosis
      factor-alpha-mediated apoptosis in human colon HT-29 cells through
      glycosphingolipids formation. Possible role of ganglioside GD3.
AB  - In the present study we assessed the contribution of acidic sphingomyelinase
      (ASMase), a ceramide generating enzyme, in tumor necrosis factor (TNF)-mediated
      apoptosis in human colon HT-29 cells. TNF induced apoptosis in HT-29 cells in a
      time- and dose-dependent fashion. Downregulation of the active endogenous ASMase
      form prevented TNF-stimulated ASMase activity and apoptosis. Furthermore,
      inhibition of glucosylceramide synthase, which blunted TNF-stimulated GD3 levels,
      abolished TNF-mediated cell death. Immunocytochemical staining revealed the co
      localization of GD3 with mitochondria induced by TNF. The knockdown of targeted
      GD3 synthase by antisense expression vector protected HT-29 cells against TNF
      induced cell death. Thus, ASMase plays a key role in TNF-induced cell death in
      human colon epithelial cells possibly through GD3 generation.

PMID- 12208521
TI  - PIAS3 (protein inhibitor of activated STAT-3) modulates the transcriptional
      activation mediated by the nuclear receptor coactivator TIF2.
AB  - PIAS3, a member of the protein inhibitor of activated STAT family, was found to
      interact in vivo and in vitro with TIF2, a previously described coactivator for
      nuclear receptors. The interaction is mediated by two distinct non-contiguous
      regions of TIF2. We found that TIF2-PIAS3 interaction occurs through a unique
      domain of PIAS3, very rich in acidic residues and conserved throughout the PIAS
      family. PIAS3 modulates the ability of TIF2 to mediate ligand-enhanced
      transcription activation positively or negatively, for different steroid
      receptors. Taken together, our results indicate a potential role of PIAS3 as
      transcriptional modulator of TIF2-mediated signalling.

PMID- 12208522
TI  - Characterization of deoxyuridine 5'-triphosphate nucleotidohydrolase from
      Trypanosoma cruzi.
AB  - We report the cloning and kinetic characterization of Trypanosoma cruzi
      deoxyuridine 5'-triphosphate nucleotidohydrolase (dUTPase) whose coding sequence
      was isolated by genetic complementation in Escherichia coli. The deduced amino
      acid sequence was similar to Leishmania major dUTPase although it exhibits an
      amino acid insertion which is sensitive to protease inactivation. The
      catalytically active species of the enzyme is a dimer and a detailed kinetic
      characterization showed that it is highly specific for dUTP and dUDP. The general
      observation that dUTPases from the Trypanosomatidae differ in sequence,
      conformation and substrate specificity suggests that a different family of
      dUTPases exists in certain organisms, which may be exploited as drug targets
      against infectious diseases.

PMID- 12208526
TI  - P300 and slow wave from oddball and single-stimulus visual tasks: inter-stimulus
      interval effects.
AB  - The effects of inter-stimulus intervals on P300 from an oddball task (target and
      standard stimuli) and a single-stimulus task (targets only) employing simple
      visual stimuli were assessed in order to determine how a relatively long ISI
      affects event-related brain potentials (ERPs). Young adult subjects (n=16)
      responded by pressing a button to a visual target stimulus of each task
      condition. ISI was either 2.5 or 30 s and paradigm type was either the oddball or
      single-stimulus task. ERPs were recorded from the midline electrodes, with
      amplitude, mean area, and latency of the P300 and other components assessed. The
      results showed that P300 morphology was dramatically affected by task and ISI
      such that under the 2.5 s condition, the oddball paradigm produced typical ERP
      components, whereas the single-stimulus condition demonstrated minimal P300
      amplitude. When ISI was 30 s, both the oddball and single-stimulus tasks produced
      robust P300 components but also evinced strong slow wave (SW) potentials, which
      contributed to the ERP measurement outcomes. It is concluded that P300 from
      visual stimuli can be elicited with both oddball and single-stimulus tasks when
      ISI is relatively long. ERPs from both paradigms produced appreciable SW
      activity, which needs to be considered when long ISI procedures are employed.

PMID- 12208527
TI  - Did I do that? An ERP study of memory for performed and planned actions.
AB  - Memory for performed and planned actions was measured on source recognition and
      source recall tests. Event-related potentials (ERPs) were recorded during the
      source recognition test to index brain activity during output monitoring. Source
      identification of performed actions was superior to planned actions and more
      performed actions were recalled, thereby replicating the enactment effect.
      Examination of recall errors revealed that more planned than performed actions
      were omitted. In addition, intrusions and source misattributions were equally
      likely when recalling planned actions, whereas more misattributions were observed
      when performed actions were recalled. The ERP data indicated that brain activity
      elicited by performed actions differed from planned and new actions. Furthermore,
      activity in the left and right frontal lobes appeared to differ for performed and
      planned actions indicating that performed actions were evaluated with more
      heuristic decision processes than both planned and new items. The temporal onset
      of the frontal ERP differences also suggests that heuristic decision processes
      begin earlier than systematic processes.

PMID- 12208528
TI  - Psychophysiological index during auditory selective attention correlates with
      visual continuous performance test sensitivity in normal adults.
AB  - The continuous performance test (CPT) provides a reliable index of cognitive
      function, but it is still unclear what aspects of processing this test measures.
      This study aimed to investigate the contribution of different aspects of
      cognitive function to the performance on degraded stimulus CPT (DSCPT), which
      requires a higher level of mental effort than the conventional CPT. Event-related
      potential (ERP) components, MMN, N2b, and early and late Nds were measured at 16
      electrode sites in 19 right-handed normal volunteers using an auditory selective
      attention task. The association between CPT sensitivity ratings (sensitivity A')
      and amplitudes of each component was examined for each electrode site. The CPT
      sensitivity A' showed a significant positive correlation with the N2b amplitude
      in the fronto-central and temporal regions, predominantly in the right hemisphere
      and specifically to the right ear of stimulation. This finding suggests that the
      controlled deviance detection process was related to DSCPT performance.

PMID- 12208529
TI  - Multifocal slow potential generation revealed by high-resolution EEG and current
      density reconstruction.
AB  - In this work we used high-resolution EEG (123 channels) and current density
      reconstruction (CDR) to analyze the generators of slow potentials (SPs) in 31
      healthy individuals. SPs were obtained during a task-performance feedback
      anticipation paradigm. The task consisted of a visual paired-associate memory
      test, with correct performance on single trials indicated by pleasant visual
      stimuli and incorrect performance by an unpleasant sound. We used realistic
      models of each subject's head based on their magnetic resonance images (MRIs) to
      estimate the potentials in the intracranial compartments and to define the source
      space using individual cortical geometry. Source reconstruction was performed by
      an Lp-norm minimization algorithm. Results showed a multifocal pattern of current
      density foci in various association cortices, including prefrontal areas 9 and 10
      of Brodmann in all subjects. Posterior cortical areas also contributed
      importantly to the SP, for instance extrastriate area 19 and parietal area 7, in
      90% of the subjects. According to our modeling, we conclude that even the pure
      stimulus-anticipation SP obtained here, as opposed to traditional motor-task
      contigent negative variation (CNVs), is not exclusively prefrontal in origin,
      being generated by multiple association areas. We discuss our results with
      respect to new possibilities in large-scale cortical physiology and with respect
      to their application in psychiatry.

PMID- 12208530
TI  - Face-specific event-related potential in humans is independent from facial
      expression.
AB  - A face-specific brain EEG potential at approximately 160 ms after stimulus
      presentation has recently been described by various research groups. Most of
      these studies analysed this face-specific brain potential using smiling faces as
      stimuli. In electrophysiological studies, however, differences in amplitude due
      to the emotional valence of the stimuli were described as early as 100 ms after
      stimulus presentation. In order to investigate the effect of facial expressions
      with different emotional content on face-specific brain EEG potentials, event
      related potentials (ERPs) to faces with sad, happy and neutral expressions were
      compared to ERPs elicited with buildings in 16 healthy subjects. A face-specific
      potential at vertex approximately 160 ms after stimulus presentation has been
      verified in the present study. No significant differences in latency or amplitude
      of this component were found for different facial expressions.

PMID- 12208531
TI  - Amplitude differences of evoked alpha and gamma oscillations in two different age
      groups.
AB  - The aim of this study was to investigate whether the amplitude of gamma-band
      activity is influenced by the factor age. We examined alpha- and gamma-band EEG
      activity and event-related potentials (ERPs) of 12 subjects. Six subjects
      constituted the younger (mean age=36.6 years) and another six the older age group
      (mean age=47.6 years). Subjects performed a visual discrimination task which
      required a response to Kanizsa squares (targets) among Kanizsa-triangles and non
      Kanizsa figures. The ERPs of the younger group revealed a significantly larger N
      170 amplitude. The amplitudes of evoked alpha- and gamma-band activity were also
      found to be significantly higher in the younger group. We discuss the
      implications of these findings and possible reasons for a change of the
      oscillatory activity in the older age group.

PMID- 12208532
TI  - Early contingent negative variation of the EEG and attentional flexibility are
      reduced in hypotension.
AB  - This study explored the question as to whether hypotension is related to
      decreased attentional performance and reduced cortical activation. A total of 50
      females aged 19-44 years participated in the study. Attentional performance was
      assessed using three subtests of the Attentional and Cognitive Efficiency (ACE)
      battery. Contingent negative variation (CNV) as a measure of cortical activation
      was registered during a constant fore-period reaction time paradigm: two
      conditions were defined using tones as S1 (80 or 60 dB) and S2 (70 dB). The
      following results were obtained. Hypotensive patients performed significantly
      more poorly on one subtest of the ACE, which indicates a reduced speed for
      switching from a routine to a controlled response (quantifying attentional
      flexibility). They also had longer reaction times and revealed a significantly
      smaller amplitude of the early CNV component. In addition, a significant
      correlation was observed between systolic blood pressure and the amplitude of the
      early CNV component. The data support previous findings that hypotension can be
      related to lowered cortical activation and indicate that specific aspects of
      attentional performance might be negatively affected by hypotension.

PMID- 12208533
TI  - Test-retest reliability of the somatosensory blink reflex and its inhibition.
AB  - Prepulse inhibition (PPI) involves inhibition of the blink reflex by a weak
      stimulus or prepulse presented immediately prior to the blink reflex-eliciting
      stimulus. Ten subjects were tested for PPI two times each day with a 60 min pause
      between tests, for 4 days spaced 1 week apart. Both the somatosensory blink
      reflex and its inhibition by an acoustic prepulse, presented 50, 100, 200, 400
      and 800 ms prior to the reflex-eliciting stimulus, were investigated. The results
      showed very high reliability for the blink reflex across all eight tests
      (Chronbach's alpha=0.98). Inhibition of the reflex by a prepulse displayed alphas
      of >0.94, and percentage of PPI also displayed significant reliability. Blink
      latency also displayed high reliability. In sum, the reliability of the
      somatosensory blink reflex and its inhibition is very high.

PMID- 12208536
TI  - Cochlear abnormalities in insulin-like growth factor-1 mouse mutants.
AB  - Insulin-like growth factor 1 (IGF-1) modulates inner ear cell proliferation,
      differentiation and survival in culture. Its function in human hearing was first
      evidenced by a report of a boy with a homozygous deletion of the Igf-1 gene, who
      showed severe sensorineural deafness [Woods et al., New Engl. J. Med. 335 (1996)
      1363-1367]. To better understand the in vivo role of IGF-1 during inner ear
      differentiation and maturation, we studied the cochleae of Igf-1 gene knockout
      mice by performing morphometric stereological analyses, immunohistochemistry and
      electron microscopy on postnatal days 5 (P5), P8 and P20. At P20, but not at P5,
      the volumes of the cochlea and cochlear ganglion were significantly reduced in
      mutant mice, although the reduction was less severe than whole body dwarfism. A
      significant decrease in the number and average size of auditory neurons was also
      evident at P20. IGF-1-deficient cochlear neurons showed increased apoptosis,
      along with altered expression of neurofilament 200 kDa and vimentin. The eighth
      nerve, the cochlear ganglion and the fibers innervating the sensory cells of the
      organ of Corti of the P20 mouse mutants presented increased expression of
      vimentin, whereas the expression of neurofilament was decreased. In addition, the
      myelin sheath was severely affected in ganglion neurons. In conclusion, IGF-1
      deficit in mice severely affects postnatal survival, differentiation and
      maturation of the cochlear ganglion cells.

PMID- 12208537
TI  - Evaluation of anesthesia effects in a rat animal model using otoacoustic emission
      protocols.
AB  - Anesthesia effects on otoacoustic emission (OAE) recordings were evaluated in a
      group of 72 Sprague-Dawley rats (mean weight 225+/-20 gr). Two anesthesia dosages
      (high and normal) and two anesthetic protocols (ketamine-xylazine, ketamine
      xylazine-atropine) were tested. Transient evoked OAE (TEOAE) and distortion
      product OAE (DPOAE) responses were recorded in 10 min intervals, for a total
      period of 60 min. Analyses of the data with repeated measure models indicated the
      following: (1) The animals receiving a high dose of anesthesia (cumulative dose
      66.6 mg of ketamine and 13.2 mg of xylazine/kg of body weight) presented
      significant alterations of the TEOAE response level and the signal to noise ratio
      at 3.0 kHz; (2) the animals receiving a normal dose of ketamine-xylazine
      anesthesia (cumulative dose 50 mg of ketamine and 10 mg of xylazine/kg of body
      weight) presented TEOAE and DPOAE responses invariant in terms of time; (3)
      significant differences were observed in the DPOAE responses from animals
      anesthetized with ketamine-xylazine and ketamine-xylazine-atropine. The data
      support the hypothesis that the ketamine anesthesia OAE suppressing mechanism is
      related to middle-ear mechanics.

PMID- 12208538
TI  - Notch/Notch ligands and Math1 expression patterns in the organ of Corti of wild
      type and Hes1 and Hes5 mutant mice.
AB  - The sensory epithelium of the mammalian cochlea (the organ of Corti) represents
      an excellent developmental system. The organ of Corti contains two main cell
      types: the sensory hair cells and the supporting cells which are organized in a
      defined mosaic pattern. Previous results have demonstrated the participation of
      Notch signaling in the regulation of the pattern of hair cell differentiation
      within this sensory mosaic. It has also been shown that the basic helix-loop
      helix (bHLH) transcription factor Math1 is a positive regulator of hair cell
      differentiation. We demonstrated that Hes1 and Hes5, two members of the
      inhibitory bHLH transcription factors, act as negative regulators of hair cell
      differentiation. Loss-of-function studies implicating the neurogenic genes
      Notch1, Jag2, Hes1 and Hes5 generated a significant increase in the number of
      hair cells. However, their functional interplay within the organ of Corti has not
      been determined. To clarify the mechanisms that regulate hair cell
      differentiation, we examined the expression of Notch/Notch ligand system and
      Math1 in the developing organ of Corti of Hes1- and Hes5-deficient mice. Our
      study suggests complex specific relationships between Notch signaling, Math1 and
      Hes1/Hes5 in the control of hair cell differentiation in the developing organ of
      Corti.

PMID- 12208539
TI  - Electrocochleography in auditory neuropathy.
AB  - Auditory neuropathy (AN) is a disorder characterized by the absence or the severe
      impairment of the auditory brainstem responses (ABRs) together with the
      preservation of otoacoustic emissions and/or cochlear microphonic (CM). We
      recorded transtympanic electrocochleography (ECohG) evoked by 0.1 ms clicks in
      one young adult and in four children having distortion product otoacoustic
      emissions and absent ABRs. In all but one patient CM and summating potential (SP)
      were present with normal threshold, and their amplitudes appeared comparable to
      or higher than the values obtained from subjects with normal hearing. The
      compound action potential (CAP) was absent in two patients while in one subject
      CM and SP were followed by a highly desynchronized neural activity. A broad CAP
      was found in two children and the threshold appeared clearly elevated in one of
      them, while it showed only a mild elevation in the other. No correlation was
      found between CAP and behavioral thresholds. These results suggest that ECohG can
      be useful in AN diagnoses since it is the only reliable tool in evaluating the
      auditory peripheral function in the presence of a desynchronized ABR.

PMID- 12208540
TI  - Identification of factors that maintain mammalian outer hair cells in adult organ
      of Corti explants.
AB  - Both outer hair cells (OHCs) and inner hair cells (IHCs) survive and mature in 3
      days old rat organ of Corti explants cultured for 1 month in a minimal essential
      medium. In contrast, under the same culture conditions, only IHCs survive in
      explants from adult guinea pig organ of Corti while many of the OHCs are lost
      within the first 48 h. Hair cell counts show OHCs loss to be greater in the lower
      portion (i.e. middle turn) of the cochlea than at the apex. Terminal
      deoxynucleotidyl transferase-mediated dUTP nick end labelling (TUNEL) indicates
      that there is DNA damage in adult OHCs within 8 h of explantation. Treatment of
      the adult organ of Corti explants with either actinomycin D (10(-7) M) or
      cycloheximide (10(-6) M) prevents most OHC losses. According to these results
      apoptosis may be the mechanism of OHC loss in adult organ of Corti explants.
      Stable membrane potentials recorded from the OHCs in both uncultured and
      actinomycin D-treated organ of Corti explants cultured for 72 h demonstrate the
      functional integrity of these hair cells. OHC losses in the adult guinea pig
      organ of Corti cultures can also be prevented by treatment with several of the
      growth factors tested, i.e. acidic fibroblast growth factor (aFGF), insulin-like
      growth factor-1 (IGF-1), epidermal growth factor (EGF), transforming growth
      factor-beta1 (TGF-beta1), and glial cell-derived neurotrophic factor (GDNF). The
      results of this study suggest that growth factor therapy may be applicable to the
      treatment of some hearing disorders.

PMID- 12208541
TI  - Aquaporin-2 expression in the mammalian cochlea and investigation of its role in
      Meniere's disease.
AB  - The expression pattern of aquaporin-2 (AQP2), a vasopressin regulated member of
      the aquaporin gene family, in the cochlea and its potential role in Meniere's
      disease was investigated. RT-PCR screen of multiple rat tissues identified AQP2
      transcripts in the cochlea, testis and kidney and an absence of tissue-specific
      splice variants. The level of AQP2 transcript in the cochlea was 10-fold lower
      relative to its expression in the testis and kidney. Western blot analysis
      demonstrated a single, 29 kDa band in the membrane fractions from cochlea, testis
      and the kidney. In the rat and mouse cochlea, AQP2 was expressed in the
      structures bordering the endolymph, including Reissner's membrane, the organ of
      Corti, inner and outer sulcus cells and the spiral limbus. A mutation screen of
      AQP2 in 12 individuals with Meniere's disease did not identify any sequence
      alterations or mutations within the four coding exons of AQP2 and their intron
      exon junctions. The physiological role of AQP2 in water transport and its
      expression pattern in the cochlea suggests an important role for AQP2 in fluid
      homeostasis of the inner ear; however, its role in the pathogenesis in Meniere's
      disease remains to be established.

PMID- 12208542
TI  - Ototoxic effects of cisplatin in a Sprague-Dawley rat animal model as revealed by
      ABR and transiently evoked otoacoustic emission measurements.
AB  - The ototoxic effects of cisplatin in a Sprague-Dawley rat model were evaluated by
      recordings of auditory brainstem responses (ABR) and transiently evoked
      otoacoustic emissions (TEOAEs). The ABR responses were evoked from alternating
      clicks and 8, 10, 12, 16, 20 and 30 kHz tone pips in a range from 40 to 100 dB
      SPL range. The TEOAEs were recorded with a non-linear protocol, and were evoked
      by a 63.5 dB SPL click stimulus. Twenty five male Sprague-Dawley rats were used
      in the study, 20 animals were treated with cisplatin (16 mg/kg, body weight) and
      five animals served as controls. The data showed that 72 h after the cisplatin
      administration, the TEOAE and ABR variables were significantly altered. The
      relationship between the ABR and TEOAE variables was shown to be non-linear. The
      most significant relationships were observed between the TEOAE correlation and
      the ABR threshold values at 10, 12, and 16 kHz.

PMID- 12208543
TI  - Tinnitus in hamsters following exposure to intense sound.
AB  - Hamsters were trained with a conditioned suppression/avoidance procedure to drink
      in the presence of a broadband noise and/or a tone and to stop drinking in the
      absence of sound. A variety of tones and loudspeaker locations were used during
      training so that the animals would respond to a sound regardless of its frequency
      or location. Four groups of animals then had their left ears exposed to a 10-kHz
      tone at 124 or 127 dB for 0.5, 1, 2 or 4 h. They were then tested for tinnitus by
      comparing their performance with that of unexposed animals to determine if they
      behaved as if they perceived a sound when no external sound was present. The
      groups exposed for 2 and 4 h tested positive for tinnitus whereas those exposed
      for 0.5 and 1 h did not. The degree of hearing loss produced by the tone exposure
      was assessed using behavioral and auditory brainstem response (ABR) procedures. A
      partial dissociation was found between the hearing loss, as estimated by the ABR,
      and the results of the tinnitus test in that animals exposed for 1 h had the same
      hearing loss as the 2- and 4-h exposed animals, but did not test positive for
      tinnitus. This suggests that the positive scores on the tinnitus test were not
      due to hearing loss. These results are discussed along with those of previous
      behavioral studies of tinnitus in animals.

PMID- 12208544
TI  - PET imaging of the normal human auditory system: responses to speech in quiet and
      in background noise.
AB  - The neural mechanisms involved in listening to sentences, and then detecting and
      verbalizing a specific word are poorly understood, but most likely involve
      complex neural networks. We used positron emission tomography to identify the
      areas of the human brain that are activated when young, normal hearing males and
      females were asked to listen to a sentence and repeat the last word from the
      Speech in Noise (SPIN) test. Listening conditions were (1) Quiet, (2) Speech, (3)
      Noise, and (4) SPIN with stimuli presented monaurally to either the left ear or
      the right ear. The least difficult listening task, Speech, resulted in bilateral
      activation of superior and middle temporal gyrus and pre-central gyrus. The Noise
      and SPIN conditions activated many of the same regions as Speech alone plus
      additional sites within the cerebellum, thalamus and superior/middle frontal
      gyri. Comparison of the SPIN condition versus Speech revealed additional
      activation in the right anterior lobe of the cerebellum and right medial frontal
      gyrus, near the cingulate. None of the left ear-right ear stimulus comparison
      revealed any significant differences except for the SPIN condition that showed
      greater activation in the left superior temporal gyrus for stimuli presented to
      the right ear. No gender differences were observed. These results demonstrate
      that repeating the last word in a sentence activates mainly auditory and motor
      areas of the brain when Speech is presented, whereas more difficult tasks, such
      as SPIN or multi-talker Noise, activate linguistic, attentional, cognitive,
      working memory, and motor planning areas.

PMID- 12208545
TI  - Sex- and age-related elevation of cochlear nerve envelope response (CNER) and
      auditory brainstem response (ABR) thresholds in C57BL/6 mice.
AB  - The C57BL/6 mouse has long been considered, in scores of published studies, as a
      model of early adult-onset, progressive sensorineural hearing loss (presbycusis).
      The auditory brainstem response (ABR) has most often been used in these studies
      as a measure of functional loss. Whereas the ABR measures the response to a rapid
      acoustic onset, the cochlear nerve envelope response (CNER) measures the ability
      of cochlear nerve axons to respond to the low frequency modulations of the entire
      acoustic waveform, acoustic changes that are utilized in vocalizations and music.
      The present study compared the ability of these two measures to assess
      presbycusis in male and female C57BL/6 mice, at ages ranging from 50 to 400 days.
      Thresholds to the CNER were almost invariably more sensitive than the ABR, in
      response to stimulus frequencies ranging from 8 to 56 kHz. By 100 days of age,
      mice showed elevation of thresholds in response to high frequency stimuli, and
      this loss was greater in females than in males. These trends persisted for both
      measures over the next 300 days, involving successively lower frequencies.

PMID- 12208546
TI  - Effects of electrical stimulation of the inferior colliculus on 2f1-f2 distortion
      product otoacoustic emissions in anesthetized guinea pigs.
AB  - The effects of electrical stimulation of the inferior colliculus (IC) on the
      activation of olivocochlear nerve fibers were investigated in guinea pigs in
      which the 2f1-f2 distortion product otoacoustic emissions (DPOAE) were recorded.
      Animals were anesthetized with ketamine (33 mg/kg) and xylazine (6.6 mg/kg).
      Bipolar electrical stimulation of the IC by a train of pulses with currents less
      than the threshold for evoking muscle twitches resulted in a small depression of
      the DPOAE amplitude by 0.1-2 dB. The maximal effect was observed when the
      stimulating electrodes were located in the rostro-medial or ventral parts of the
      IC. The suppression of electrically evoked DPOAE was similar to the DPOAE
      suppression produced by acoustical stimulation of the contralateral ear by a
      broad-band noise. Suppression of DPOAE amplitude in response to both acoustical
      and electrical stimulation was abolished 1-2 h after a single intramuscular
      injection of gentamicin (210-250 mg/kg). The results indicate that electrical
      stimulation of the IC can activate the efferent system and produce DPOAE changes
      by similar mechanisms as does acoustical stimulation of the contralateral ear.

PMID- 12208547
TI  - Distribution of ectonucleoside triphosphate diphosphohydrolases 1 and 2 in rat
      cochlea.
AB  - Extracellular ATP and other extracellular nucleotides acting via P2 receptors in
      the inner ear initiate a wide variety of signalling pathways important for
      regulation of hearing and balance. Ectonucleotidases are extracellular nucleotide
      metabolising enzymes that modulate purinergic signalling in most tissues. Major
      ectonucleotidases in the cochlea are likely members of the ectonucleoside
      triphosphate diphosphohydrolase (E-NTPDase) family. In this study, we provide a
      detailed description of NTPDase1 and NTPDase2 distribution in cochlear tissues
      using immunocytochemistry. E-NTPDase immunoreactivity was not equally distributed
      in the tissues bordering scala media. It was observed in the organ of Corti,
      including sensory and supporting cells, but was notably absent from Reissner's
      membrane and most of the marginal cells of the stria vascularis. NTPDase1
      expression was most prominent in the cochlear vasculature and cell bodies of the
      spiral ganglion neurones, whereas considerable NTPDase2 immunoreactivity was
      detected in the stria vascularis. Both E-NTPDases were expressed in the cuticular
      plates of the sensory hair cells and nerve fibres projecting from the synaptic
      area underneath the inner and outer hair cells. E-NTPDase localisation
      corresponds to the reported distribution of some P2X receptor subunits (P2X(2) in
      particular) in sensory, supporting and neural cells and also P2Y receptor
      distribution in the vasculature and secretory tissues of the lateral wall. The
      role for E-NTPDases in purinergic signalling is most likely to regulate
      extracellular nucleoside triphosphate and diphosphate levels and thus provide
      termination for extracellular ATP signalling that has been linked to control of
      cochlear blood flow, electrochemical regulation of sound transduction and to
      neurotransmission in the cochlea.

PMID- 12208548
TI  - Time course and quantification of changes in cochlear integrity observed in
      commercially raised broiler chickens.
AB  - Extensive cochlear hair cell damage and loss occurs in aged broiler chickens. We
      describe the time course and several characteristics of this decline in cochlear
      integrity in 19-, 30-, 38- and 66-week-old commercially raised broiler chickens.
      The 19-week-old group is normal and serves as a baseline for comparison.
      Generally, cochlear damage increases in severity and percent length of the
      cochlea with age. Hair cell density increases from the base to the apex. Density
      is similar across the groups in regions of the cochlea that sustained little or
      no damage, and decreases in regions of extreme damage. Counts of normal and
      abnormal hair cells are inversely related. A subset of 66-week-old birds has
      higher density measurements and increased hair cell counts in the apical region
      of the cochlea. The progressive damage found in these commercially raised birds
      is described in the context of both the effects of age and noise exposure on the
      auditory system. Two additional groups of birds were raised at the University of
      Kansas Medical Center in a quieter environment to determine the cause of the
      damage seen in age-matched commercially raised birds. These cochleae are largely
      normal; a small number displayed damage. This suggests that noise exposure
      exacerbates naturally occurring cochlear degradation.

PMID- 12208549
TI  - Hsp70 in the inferior colliculus of Fischer-344 rats: effects of age and acoustic
      stress.
AB  - Heat shock proteins 72 and 73 (hsp72 and hsp73) were studied in the inferior
      colliculus (IC) of Fischer-344 rats to determine if their levels are altered
      during normal aging and following exposure to intense acoustic noise. Three age
      groups of rats (3, 18, and 25 months) were exposed to ambient sound (control) or
      broad-band noise at 108 dB sound pressure level (0.0004 dyn/cm2) for 30 min.
      Western blotting procedures were used to measure hsp72 and hsp73 in ICs and
      cerebella (positive control). Immunohistochemistry was performed using 3-month
      olds to study the localization patterns of hsp72 and hsp73 in both structures.
      The IC and cerebellum exhibited immunolabeling over neuronal somata and proximal
      dendrites. Ambient levels of hsp72 in supernatants from aged rats were reduced
      56.5%+/-7.8% in the IC relative to 3-month olds. This decrease may render the IC
      more susceptible to stress-related damage. An increase in constitutive hsp73
      (350.7%+/-70.4%) was observed in IC pellet fractions from animals exposed to the
      108-dB noise when compared to the ambient-noise controls, suggestive of a
      lipoprotective role for hsp73. This elevation was consistent across age groups.
      No noise-induced changes in hsp72 were detectable in the IC, indicating that loud
      sounds may not be an appropriate stimulus for hsp72 induction in this structure.

PMID- 12208550
TI  - Asymmetric hemodynamic responses of the human auditory cortex to monaural and
      binaural stimulation.
AB  - Applying whole-head functional magnetic resonance imaging (fMRI) in 11
      neurologically intact subjects, hemodynamic responses to mon- or binaurally
      presented auditory stimuli were measured. To expand on previous studies in this
      research area, we used tones and consonant-vowel (CV) syllables. In one group of
      subjects (n=6) the perceived loudness of the monaurally presented stimuli were
      adjusted so that they matched the loudness of the binaurally presented stimuli.
      In a second group (n=5) no loudness adjustment was performed, thus the monaural
      stimuli were perceived less loud ( approximately 10 dB) than the binaural
      stimuli. These extensions allowed us to test whether CV syllables and tones
      produce different contralaterality effects (stronger hemodynamic responses in the
      auditory cortex contralateral to the stimulated ear) and whether binaural
      stimulation results in stronger activations in the auditory areas than during
      both monaural stimulation conditions (binaural summation) independent of loudness
      influences. In summary, we obtained the following findings: (1) strong
      contralaterality effects during monaural acoustic stimulation in the posterior
      superior temporal gyrus (STG) comprising the planum temporale and the dorsal bank
      of the superior temporal sulcus to CV syllables and tones; (2) the hemodynamic
      responses to contralaterally presented stimuli (during the monaural conditions)
      were mostly stronger than those to binaurally presented CV syllables; (3) there
      was no interaction between stimulus type and the size of the contralaterality
      effect; (4) there was no indication of binaural summation, rather we found
      stronger hemodynamic responses to the sum of both monaural stimulations (right
      and left ear) than to binaural stimulation in all auditory areas; (5) there were
      generally stronger hemodynamic responses to CV syllables than to tones in the
      posterior STG, while the hemodynamic responses to tones were stronger in the
      anterior part of the STG (temporal pole); and finally (6) there was no general
      difference in terms of hemodynamic response in the auditory cortex between the
      two groups when receiving either loudness-matched or non-loudness-matched
      monaural stimulation. These findings are discussed in the context of the
      underlying neurophysiological mechanisms, the peculiarities of functional fMRI,
      and the direct access and callosal relay models of hemispheric lateralization.

PMID- 12208551
TI  - Electrophysiological characteristics of inferior colliculus neurons in mutant
      mice with hereditary absence of cochlear outer hair cells.
AB  - One strain of homozygous Kit(W-v) mice (formerly known as W(v)/W(v)) lack 98% of
      the cochlear outer hair cells (OHCs) from birth. Inner hair cells (IHCs) and
      supporting cells develop normally. Thus, this strain is an attractive model to
      study the effect of complete OHC absence on central frequency representation.
      Frequency threshold curves were recorded along the tonotopic axis of inferior
      colliculus (IC) in mutant and control mice of the genetic background strain
      (C57BL/6J) and a different outbred strain (NMRI/wild mouse hybrids) known to be
      free of any cochlear pathology. The average threshold level of neurons in the
      mutants was 100 dB sound pressure level, 60 dB higher than in C57BL/6J and NMRI
      mice. Their tuning curves lacked the sharply tuned tip. In the C57BL/6J mice,
      although younger than four months, abnormal tuning curves were found for about
      30% of the neurons, especially in the high frequency range. No abnormal tuning
      curves were found in the NMRI mice. The bandwidth of the tuning curves, measured
      at 10 dB above threshold, was on average 1.27 octaves in mutants, 0.62 octaves in
      C57BL/6J mice, and 0.34 octaves in NMRI mice. The range for the high cut-off
      frequency of the tuning curves at 10 dB above threshold was 6.4-61.1 kHz in the
      NMRI and 7-59.5 kHz in C57BL/6J. In the mutants, the range was limited to 11.1
      41.7 kHz. The tonotopic gradient based on the cut-off frequency was less steep in
      the IC of the mutants than in both control groups.

PMID- 12208552
TI  - A three-dimensional nonlinear active cochlear model analyzed by the WKB-numeric
      method.
AB  - A physiologically based nonlinear active cochlear model is presented. The model
      includes the three-dimensional viscous fluid effects, an orthotropic cochlear
      partition with dimensional and material property variation along its length, and
      a nonlinear active feed-forward mechanism of the organ of Corti. A hybrid
      asymptotic and numerical method combined with Fourier series expansions is used
      to provide a fast and efficient iterative procedure for modeling and simulation
      of the nonlinear responses in the active cochlea. The simulation results for the
      chinchilla cochlea compare very well with experimental measurements, capturing
      several nonlinear features observed in basilar membrane responses. These include
      compression of response with stimulus level, two-tone suppressions, and
      generation of harmonic distortion and distortion products.

PMID- 12208553
TI  - Drug treatment of conduct disorder in young people.
AB  - Although conduct disorder (CD) is the most common psychiatric disorder in youth
      from the community and encompasses one third to one half of all referrals to
      child and adolescent clinics, there is no licensed drug, to date, for treatment
      of CD, neither in Europe nor in the US. The aims of this paper are to review
      research data available on the use of medication for CD in young people and to
      identify future directions for research. We review 17 controlled studies and six
      open trials. Investigated compounds mainly belong to three classes of
      psychotropic drugs: mood stabilizers, neuroleptics and stimulants (six, five and
      six controlled studies, respectively). Lithium is the most documented treatment
      (3/4 positive studies). Conventional neuroleptics have been most commonly
      prescribed (3/3 positive studies), atypical neuroleptics appear promising (2/2
      positive studies). Methylphenidate improves some CD symptoms, even in the absence
      of ADHD (6/6 positive studies). Sparse research has been conducted on response to
      antidepressants. The evidence for an effective role of pharmacotherapy in CD is
      still limited. Treatment should be multimodal and individualized to each
      patient's specific condition.

PMID- 12208554
TI  - The contribution of cytochrome P-450 isoenzymes to the metabolism of
      phenothiazine neuroleptics.
AB  - The aim of the present study was to determine optimum conditions for studying
      promazine and perazine metabolism in rat liver microsomes, and to investigate the
      influence of specific cytochrome P-450 inhibitors on 5-sulfoxidation and N
      demethylation of these neuroleptics. Based on the developed method, the
      metabolism of neuroleptics in liver microsomes was studied at linear dependence
      of product formation on time, and protein and substrate concentrations
      (incubation time: 10 min; concentration of microsomal proteins: promazine-0.7 mg
      ml(-1), perazine-0.5 mg ml(-1); substrate concentrations: promazine-25, 40 and 75
      nmol ml(-1), perazine-20, 35, 50 nmol ml(-1)). A Dixon analysis of the metabolism
      of neuroleptics showed that quinine (a CYP2D1 inhibitor), metyrapone (a CYP2B1/B2
      inhibitor) and alpha-naphthoflavone (a CYP1A1/2 inhibitor) affected, whereas
      erythromycin (a CYP3A inhibitor) and sulfaphenazole (a CYP2C inhibitor) did not
      change the neuroleptic biotransformation. N-Demethylation of promazine was
      competitively inhibited by quinine (K(i)=20 microM) and metyrapone (K(i)=83
      microM), while that of perazine-by quinine (K(i)=46.5 microM), metyrapone
      (K(i)=46 microM) and alpha-naphthoflavone (K(i)=78.8 microM). 5-Sulfoxidation of
      promazine was inhibited only by quinine (K(i)=28.6 microM), whereas that of
      perazine-by quinine (K(i)=10 microM) and metyrapone (K(i)=96 microM). The results
      obtained are compared with our previous findings of analogous experiments
      concerning thioridazine, and with the data on other phenothiazines and species.
      In summary, it is proposed that N-demethylation of the mentioned phenothiazine
      neuroleptics in the rat is catalyzed by the isoenzymes CYP2D1, CYP2B2 and CYP1A2
      (CYP1A2 does not refer to promazine). 5-Sulfoxidation of these drugs may be
      mediated by different isoenzymes, e.g. CYP2D1 (promazine and perazine), CYP2B2
      (perazine) and CYP1A2 (thioridazine). Isoenzymes belonging to subfamilies CYP2C
      and CYP3A do not seem to be involved in the metabolism of the investigated
      neuroleptics in the rat. The results obtained point to the drug structure and
      species differences in the contribution of cytochrome P-450 isoenzymes to the
      metabolism of phenothiazines.

PMID- 12208555
TI  - Biochemical effects in brain of low doses of haloperidol are qualitatively
      similar to those of high doses.
AB  - Typical and atypical antipsychotic drugs (APD) show differential effects in brain
      on both dopamine output and activation of Fos-like immunoreactivity (FLI) in
      dopamine nerve terminal regions. Typical APD increase dopamine output
      preferentially in the core and atypical APD increase dopamine output
      preferentially in the shell of the nucleus accumbens (NAC). Whereas both typical
      and atypical APD increase FLI in NAC, typicals cause FLI activation in the
      striatum and atypicals cause FLI activation in the prefrontal cortex. Clinically,
      low doses of haloperidol cause less side-effects than higher doses, and low-dose
      haloperidol has been suggested as a cost-effective alternative to atypical APD.
      Here, in vivo voltammetry in anaesthetised, pargyline-pretreated rats was used to
      measure dopamine output in the two subdivisions of the NAC and, in addition,
      immunohistochemistry was used to assess FLI activation in dopamine target areas,
      following acute haloperidol administration. Haloperidol, 0.001 and 0.01 mg/kg
      i.v., caused a significantly higher dopamine output in the core than in the shell
      of the NAC. Moreover, haloperidol 0.05 and 0.5, but not 0.005, mg/kg s.c.
      increased FLI in the NAC and the striatum, but not in the medial prefrontal
      cortex. Thus, even extremely low doses of haloperidol generate, in principle, the
      same biochemical effects in brain as higher doses, and these effects remain
      different from those of atypical APD. These biological data indicate that
      clinical differences between haloperidol and atypicals are qualitative rather
      than dose-dependent. Consequently, our results do not support the use of low-dose
      haloperidol as replacement for atypical APD in the treatment of schizophrenia.

PMID- 12208556
TI  - Effects of 5-HT(1B) receptor ligands microinjected into the accumbal shell or
      core on the sensitization to cocaine in rats.
AB  - The present study was designed to find out whether 5-HT(1B) receptors located in
      subareas of the nucleus accumbens played a role in cocaine sensitization in rats,
      and whether pharmacological activation of these receptors could modify this drug
      effect. Male Wistar rats implanted bilaterally with cannulae into the accumbens
      shell or core were microinjected with GR 55562 (an antagonist of 5-HT(1B)
      receptors) or CP 93129 (an agonist of 5-HT(1B) receptors). The rats, which were
      repeatedly (for 5 days) administered with cocaine (10 mg/kg) and then challenged
      with cocaine (10 mg/kg) after 5-day withdrawal period, showed significantly
      higher locomotor hyperactivity in comparison with the effect observed in saline
      pretreated and cocaine challenged rats. GR 55562 (0.1-10 microg/side),
      administered for 5 days into the accumbens shell, but not into the core, prior to
      cocaine dose-dependently attenuated cocaine sensitization. When injected for 5
      days into either the accumbens shell or core before cocaine, CP 93129 (0.1-10
      microg/side) had no effect on the development of cocaine sensitization. To
      examine the effects of GR 55562 and CP 93129 on the expression of cocaine
      sensitization, the drugs were given acutely before a challenge dose of cocaine
      (10 mg/kg) on day 10. No change in cocaine sensitization was observed after
      injection of GR 55562 (0.1-10 microg/side) to the either accumbens subregion or
      after injection of CP 93129 (0.1-10 microg/side) into the core. However, an intra
      accumbens shell injection of CP 93129 (10-30 microg/side) increased sensitization
      to cocaine, and this enhancement was attenuated after local injection of GR 55562
      (1 microg/side). Our findings indicate that behavioral sensitization to cocaine
      may be modulated by 5-HT(1B) receptor ligands in the accumbens shell, but not
      into the core. They suggest that the inhibition of 5-HT(1B) receptors in the
      accumbens shell attenuates the development, whereas their pharmacological
      activation enhances the expression of cocaine sensitization.

PMID- 12208557
TI  - Cerebral distribution of polyamines in kainic acid-induced models of status
      epilepticus and ataxia in rats. Overproduction of putrescine and histological
      damage.
AB  - We study the brain regional distribution of putrescine after excitotoxic damage.
      After status epilepticus induced by kainic acid (9 mg/kg, i.p.) we found an
      increase of putrescine in all the regions analyzed. Three kind of regions can be
      identified according to the magnitude and persistence of the abnormal
      concentration of putrescine: hippocampus and cortex (9-fold 1 day, still
      increased 2-fold 2 weeks after injection), cerebellum and medulla oblongata+pons
      (2-fold 1 day after injection) and the other regions (7-8-fold 1 day, still
      increased 2-3-fold 1 week after injection). The histological damage was: severe,
      absent and moderate or low, respectively. After ataxia induced by kainic acid
      injection (2.34 nmols) into the cerebellum, putrescine also rises in all regions;
      a high concentration (9-fold) and severe damage was found in the injected
      cerebellar hemisphere. In conclusion, in the models studied, putrescine increases
      in all the regions analyzed. However, the highest concentrations and the most
      severe damage were found in the target regions.

PMID- 12208558
TI  - Effect of daily dosing duration of direct and indirect dopamine receptor
      agonists: cocaine cross-tolerance following chronic regimens.
AB  - One therapeutic paradigm for cocaine abuse is a 24-h 'agonist' treatment which
      reduces reinforcing effects in a manner similar to the methadone maintenance
      model for heroin. However, 24-h dosing of dopamine (DA) agonists may induce side
      effects of insomnia and psychosis, as well as anergia and anhedonia which may
      actually potentiate abuse. Thus, it is important to determine the daily dose
      duration of potential treatments such as direct (e.g. pramipexole) and indirect
      (e.g. GBR 12909) DA agonists, that may induce cross-tolerance with cocaine. We
      gave a cocaine challenge (15 mg/kg i.p.) on withdrawal day 7 and recorded
      ambulations and a behavioral rating. We found that 20- and 24-, but not 16-h,
      daily dosing with cocaine (40 mg/kg), for 14 days, induced tolerance. Pramipexole
      (4 mg/kg), administered for 24 but not 12 h per day, for 14 days, induced cocaine
      cross-tolerance while GBR 12909 (18 mg/kg), administered i.p. over 24 or 16 h a
      day, for 7 days, did not. Thus daily dosing duration is an important variable in
      consideration of stimulant abuse treatment.

PMID- 12208559
TI  - Modulation of tianeptine on ion currents induced by inhibitory neurotransmitters
      in acutely dissociated dorsal raphe neurons of Sprague-Dawley rats.
AB  - Classical antidepressant therapy has mainly used selective serotonin reuptake
      inhibitors (SSRIs) and tricyclic antidepressants (TCAs), but tianeptine appears
      to possess effects on 5-hydroxytryptamine (5-HT, serotonin) levels in the
      synaptic cleft contradictory to those of SSRIs. The mechanism behind its
      antidepressant effects is still unclear. The effect of tianeptine on the
      electrophysiological characteristics of neurons in the dorsal raphe, where
      serotonergic neurons mainly originate from, were investigated by the patch-clamp
      method in the present study. Tianeptine was shown to inhibit the ion currents
      induced by the inhibitory neurotransmitters GABA and glycine as well as the
      inwardly rectifying K(+) current induced by 5-HT and 8-hydroxy-2 (di-n
      propylamino) tetraline hydrobromide (8-OH-DPAT), a 5-HT(1A) agonist. Tianeptine,
      however, exerted no effect on the ion current induced by the excitatory
      neurotransmitter glutamate. These results indicate that tianeptine has an
      inhibitory effect on ion currents evoked by GABA, glycine, and inwardly
      rectifying K(+) current induced by 5-HT in the dorsal raphe. This action may
      increase the excitability of serotonergic neurons of the dorsal raphe.

PMID- 12208560
TI  - [11C]Mirtazapine for PET neuroimaging: radiosynthesis and initial evaluation in
      the living porcine brain.
AB  - We radiolabelled mirtazapine, a tetracyclic, atypical, antidepressant drug, for
      positron emission tomography (PET) and evaluated its regional kinetics in the
      living porcine brain. We produced [N-methyl-11C]mirtazapine with a radiochemical
      purity >98% in a 21% decay-corrected radiochemical yield by alkylation of N
      desmethyl mirtazapine with [11C]methyl iodide, followed by HPLC purification and
      formulation. [N-Methyl-11C]mirtazapine entered the brain readily and, under
      baseline conditions, it had an apparent volume of distribution (V(e)') of 9-13 in
      the basal ganglia, thalamus, and frontal cortex. Reference region and graphical
      analyses based on a one-compartment model showed that the binding of [N-methyl
      11C]mirtazapine was reversible, with an apparent binding potential of more than
      two in thalamus and frontal cortex. Infusion of unlabelled mirtazapine markedly
      displaced [N-methyl-11C]mirtazapine from binding sites in the basal ganglia,
      thalamus and frontal cortex, but not in reference regions (cerebellum and
      olfactory tubercle). Thus, [N-methyl-11C]mirtazapine showed rapid passage into
      the living brain, slow metabolism in blood, and reversible, competitive binding,
      which may make it useful for PET neuroimaging of neuroreceptors involved in
      antidepressant actions.

PMID- 12208561
TI  - Enantiomers' potential in psychopharmacology--a critical analysis with special
      emphasis on the antidepressant escitalopram.
AB  - Stereochemistry is now influencing most areas of pharmacotherapy, with a growing
      awareness in the field of psychiatry and, more specifically, depression. This is
      due to the fact that the enantiomers of many chiral drugs may have distinct
      pharmacological, pharmacokinetic and/or pharmacogenetic profiles. Consequently,
      in some instances there may be an advantage in using a single enantiomer over the
      racemic form-thus providing a basis for the development of new therapeutic
      agents, as well as the potential to improve current treatments. This review
      highlights some of the potential advantages and disadvantages that using single
      enantiomers might offer. The principles are exemplified through reference to the
      stereoselective properties of several established chiral psychotropic drugs,
      including thioridazine, methadone, trimipramine, mianserin, mirtazapine,
      fluoxetine and citalopram. Emphasis is given to the treatment of depression and
      how the potential of one pure enantiomer-escitalopram, the S-enantiomer of the
      selective serotonin reuptake inhibitor citalopram-appears to be fulfilling its
      preclinical promise in the clinic.

PMID- 12208562
TI  - Effect of 5-HT in mianserin-pretreated rats on the structure of feeding behavior.
AB  - The present study examined the effects of intra-PVN serotonin injection in
      mianserin-pretreated rats at the onset of the dark phase of light cycle on the
      structure of feeding behavior. The drugs were injected into the paraventricular
      nucleus (PVN) of the hypothalamus. The animals were maintained in a self
      selection feeding paradigm and provided with freely available and separate
      sources of protein, carbohydrate, fat and water. The suppressive effect of 5-HT
      on carbohydrate intake was attenuated by mianserin at the beginning of the active
      (dark) feeding period. Mianserin-pretreatment increased the duration of
      carbohydrate and protein intake, but it was unable to block the effect of 5-HT on
      meal frequency and local rate of carbohydrate consumption. The present data
      suggests that carbohydrate intake may be in part mediated by postsynaptic 5
      HT(2A/2C) receptors. However, the temporal characteristics of carbohydrate
      ingestion are mediated by another subpopulation of 5-HT receptors in the PVN and
      indicates a possibly adrenergic influence.

PMID- 12208563
TI  - Efficacy of citalopram in anorexia nervosa: a pilot study.
AB  - INTRODUCTION: Anorexia nervosa (AN) still lacks a defined treatment. Since
      fluoxetine proved effective in weight-restored anorexics, this pilot study
      evaluates the efficacy of another SSRI, citalopram, in restricting-type AN.
      EXPERIMENTAL PROCEDURES: Fifty-two female anorectic outpatients were randomized
      in the citalopram (n=26) and waiting list (n=26) as a control group. Efficacy was
      assessed using Eating Disorder Inventory-2, Eating Disorder Inventory-Symptom
      Checklist, State-Trait Anger Expression Inventory, Beck Depression Inventory,
      Symptom Checklist-90 and Structured Clinical Interview for DSM-IV Axis II
      Disorders. RESULTS: Thirteen patients dropped-out, thus 19 patients received
      citalopram and 20 remained in the control group. After 3 months of treatment, the
      citalopram group showed a decrease on BDI and SCL-90 Depression subscale and an
      improvement of baseline obsessive compulsive features on SCL-90, EDI-2
      impulsiveness and Trait-anger on STAXI. Weight gain was similar in the two
      groups. DISCUSSION: These preliminary results support the efficacy of citalopram
      in anorectics. Citalopram seems to improve depression, obsessive-compulsive
      symptoms, impulsiveness and Trait-anger.

PMID- 12208564
TI  - The role of noradrenaline and selective noradrenaline reuptake inhibition in
      depression.
AB  - Depression is a common disorder that impacts on all aspects of a person's life.
      For the past 10 years, clinicians have focused on serotonin in their treatment of
      depression. This is largely due to the growing acceptance of the efficacy and
      safety of the selective serotonin reuptake inhibitors (SSRIs) in comparison with
      older tricyclic antidepressants (TCAs). However, evidence for a role of
      noradrenaline in depression has been accumulating for some time, beginning with
      the discovery that drugs which either caused or alleviated depression acted to
      alter noradrenaline metabolism. Until recently, the role of noradrenaline in
      depression was predicted from clinical experience with noradrenergic TCAs
      (desipramine, nortriptyline and protriptyline) and selective serotonin and
      noradrenaline reuptake inhibitors (venlafaxine, milnacipran). The licensing of
      reboxetine, a selective noradrenaline reuptake inhibitor now allows the role of
      noradrenaline in depression to be investigated directly. This review presents key
      data from the literature that support a role for noradrenaline in depression
      taking into account neurophysiology, psychopharmacology and clinical trial data.

PMID- 12208565
TI  - No association between the serotonergic polymorphisms and incidence of nausea
      induced by fluvoxamine treatment.
AB  - We investigated the association between serotonergic polymorphisms and incidence
      of nausea, which is the most frequent side-effect of selective serotonin reuptake
      inhibiters (SSRIs), in 66 patients treated with fluvoxamine in a protocolized
      dosing method. We focused on three polymorphisms of serotonin (5-HT) neuronal
      systems such as 5-HT transporter (5-HTT) gene-linked polymorphic region (5
      HTTLPR), a variable number of tandem repeat (VNTR) polymorphism in the second
      intron of the 5-HTT gene (STin2) and tryptophan hydroxylase (TPH) gene
      polymorphism in intron 7 (TPH-A218C), which have been reported to possess
      positive association with treatment response to SSRIs. In addition to this, the
      relationship between development of nausea and treatment response was also
      analyzed. Results suggested that these three polymorphisms did not affect the
      development of fluvoxamine-induced nausea, and that incidence of nausea was not a
      phenomenon that predicts the treatment response to fluvoxamine.

PMID- 12208566
TI  - The protein kinase A in platelets from patients with panic disorder.
AB  - Although previous studies suggested that dysfunctions in the protein kinase A
      (PKA) and in some of its substrates are associated with several psychiatric
      disorders, there is no evidence regarding the possible involvement of such
      components in panic disorder (PD). Thus, the aim of the present study was to
      investigate the levels of PKA and Rap1 in platelets from patients with such
      disorder. Twenty-four drug free patients with PD and 24 healthy volunteers
      participated to the study. Employing the Western Blot analysis, immunostaining
      and computer-assisted imaging, the levels of the regulatory (R, type I and type
      II) and the catalytic (C) subunits of PKA, and those of Rap1 were assessed in
      platelets from the two groups. The data show that patients with PD have
      significantly higher levels of platelet RI and C subunits of PKA than controls,
      whereas the levels of RII were unchanged. No significant differences were found
      in the immunolabelling of Rap1 between groups. These findings may provide clues
      toward understanding the involvement of cAMP signalling in anxiety disorders.

PMID- 12208567
TI  - Vasopressin in CSF and plasma in depressed suicide attempters: preliminary
      results.
AB  - Increased plasma arginine vasopressin (AVP) concentrations have been reported in
      depressed suicide attempters. Plasma AVP is primarily produced by the
      magnocellular system in response to increased plasma osmolality, and central AVP
      may be independently regulated. In the present study we investigated
      cerebrospinal fluid (CSF) and plasma AVP concentrations in depressed patients and
      controls. Nineteen drug-free depressed psychiatric inpatients (nine suicide
      attempters) and nine neurological control subjects underwent lumbar puncture and
      psychiatric evaluation. CSF and plasma concentrations of AVP, serotonin (5-HT), 5
      hydroxyindoleacetic acid (5-HIAA), homovanillic acid (HVA), and cortisol were
      assayed. In 15 depressed patients (eight suicide attempters), the combined
      dexamethasone/corticotropin-releasing hormone (Dex/CRH) test was performed to
      examine the hypothalamic-pituitary-adrenocortical (HPA) system. There were no
      differences between depressed subjects and controls in all parameters measured.
      Suicide attempters did not differ from nonattempters. In depressed patients,
      plasma AVP correlated positively with cortisol. There was no relationship between
      CSF AVP and monoamine metabolites in CSF.

PMID- 12208568
TI  - Relationships between DVHs and late rectal bleeding after radiotherapy for
      prostate cancer: analysis of a large group of patients pooled from three
      institutions.
AB  - BACKGROUND: Accurate modeling of late rectal reactions needs the collection of
      individual 3D dose-volume data (i.e. DVH) as well as clinical information of
      large cohorts of patients. The possibility of collecting a large number of
      patients with many different dose-volume combinations is very suitable for this
      purpose. PURPOSE: The purpose of the study is to search for significant
      correlation between dose-volume histograms/dose statistics of the rectum and late
      rectum bleeding. MATERIALS AND METHODS: Data from three institutions for 402
      patients previously treated for prostate cancer with three to four field
      techniques, were retrospectively pooled and were collected with a number of
      clinical and physical parameters, including DVHs of the rectum (including
      filling). Patients with large air/fecal content in the rectum during planning
      computerized tomography (CT) scan were excluded from the analysis (n = 74). Out
      of 328 patients, 229 patients received an ICRU dose between 70 and 76Gy and the
      current analysis is referred to this subgroup of patients (median follow up: 30
      months, range: 12-85 months). Out of these 229 patients, 189 patients were
      treated with conformal techniques. Rectum was contoured from the anal verge up to
      the sigmoid flessure by one observer for each institution. Dosimetric and
      contouring consistencies between the three institutions were previously
      investigated and the impact on DVHs was found to be quite modest for the purposes
      of the study. Median/quartile values of all parameters were considered as cut-off
      values for statistical analysis. We considered as bleeders those patients who
      experienced grades II-III late bleeding (modified RTOG scoring scale). RESULTS:
      Twenty two of 229 patients experienced > or =grade II late bleeding (30 months
      actuarial incidence: 10.7%). Significant correlation between a number of
      parameters and late bleeding was found (log-rank test). With regard to DVH, all
      median and third quartile values for V50-V70 were found to be significantly
      associated with an increased risk of rectal bleeding, if excepting the median
      value of V70. Based on the results of univariate analysis, the patients were
      divided into two groups: 'high risk', with at least one value above quartiles in
      the range V50-V60 (V50: 70%, V55: 64%, V60: 55%); 'low risk', the remaining
      patients. The 30 months actuarial rates of bleeding were 19.2 and 5.9% for the
      'high' and the 'low' risk group, respectively (P = 0.0003 log-rank test). A
      multivariate analysis (Cox regression model) including 'DVH grouping' and the
      main remaining variables (age, previous prostatectomy, diabetes, hypertension,
      adjuvant hormonal therapy, rectum volume and ICRU dose) showed that 'DVH
      grouping' is the most predictive parameter (P = 0.005) together with adjuvant
      hormonal therapy (P = 0.025) and ICRU dose (P = 0.06). CONCLUSIONS: Our data
      confirm the role of the rectal DVH in separating groups of patients having
      prostate radiotherapy in low and high risk of developing late bleeding. Based on
      these results, V50 below 60-65% and V60 below 50-55% seem to be the robust cut
      off values to keep the risk of developing late rectal bleeding reasonably low.
      However, due to the 'heterogeneity' of the considered population, the results
      found should be applied with caution in 'more homogeneous' groups of patients.
      The association of adjuvant hormone deprivation seems to be associated with an
      increased risk of rectal toxicity; the mechanism for this effect should be a
      focus of further research.

PMID- 12208569
TI  - External beam radiotherapy of choroidal metastases--final results of a
      prospective study of the German Cancer Society (ARO 95-08).
AB  - PURPOSE: In 1994 a prospective study of the 'Arbeitsgemeinschaft Radiologische
      Onkologie' of the German Cancer Society was initiated to examine the results of a
      standardized radiation therapy for choroidal metastases with 40 Gy.
      Recommendations in the literature vary from 21 to 50 Gy of total dose and from 2
      to 5 Gy per single fraction. To date, no larger series treated with both a
      standardized technique and dose has been reported. PATIENTS AND METHODS: Between
      1994 and 1998, 56 patients were enrolled and 50 patients with 65 involved eyes
      were available for analysis. Thirty-five patients (70%) had unilateral and 15
      patients (30%) had bilateral choroidal metastases. Fifty eyes (77%) were
      symptomatic and 15 eyes (23%) were asymptomatic. Thirty-one patients (62%) had
      breast cancer and 13 patients (26%) lung cancer as the primary tumor. Patients
      were treated with 40 Gy in 20 fractions with bilateral asymmetric fields for
      bilateral or a unilateral field for unilateral choroidal metastasis. Seventeen
      patients had additional chemotherapy after radiotherapy for general tumor
      progression. RESULTS: With a median follow-up of 5.8 months (1-44 months) 41 out
      of 50 patients were dead. The median survival of all patients was 7 months and
      for patients with breast cancer 10 months. Of the 50 symptomatic eyes visual
      acuity increased for two or more lines in 36% (18/50), was stabilized in 50%
      (25/50 eyes), and decreased in 14% (7/50). No patient with asymptomatic
      metastasis (n = 15 eyes) developed ocular symptoms during follow-up. No patient
      with unilateral tumor and unilateral irradiation developed contralateral
      metastasis. Severe side effects, possibly related to tumor progression, occurred
      in three eyes (5%). CONCLUSION: Radiation therapy with 40 Gy is an effective and
      safe palliative treatment for symptomatic and asymptomatic choroidal metastases
      to preserve vision in the majority of the patients. A unilateral field for
      unilateral metastasis seems to be sufficient to prevent contralateral disease.
      Side effects of radiotherapy are acceptable: 50% of patients developed a mild
      skin erythema and conjunctivitis (RTOG I). Late side effects were seen in three
      eyes (5%).

PMID- 12208570
TI  - Twice-a-day radiotherapy for head and neck cancer: the Catalan Institute of
      Oncology experience.
AB  - PURPOSE: The purpose of this work is to evaluate the contribution of
      hyperfractionated radiotherapy (RT) in head and neck cancer by sub-localisation.
      PATIENTS AND METHODS: From 1992 to 1999, 318 patients with squamous head and neck
      tumours treated by hyperfraction RT were analysed according to their sub
      localisation and stage. Fractions used were 1.2 Gy twice-a-day with a curative
      intent on all patients, to a total mean dose of 79.14 Gy. Treatment protocols by
      localisation were: larynx: 55 patients with T2N0 and T1-2N1 tumours treated with
      only RT and 27 patients with T3N0-1 in complete remission after three cycles of
      induction chemotherapy (ICT); hypopharynx: 29 patients with T2-4N0-2b resectable
      tumors in response to three cycles of ICT; oropharynx: 48 patients with T2-3N0-1
      and T1N1 tumours treated with only RT; 34 patients with nasopharynx tumours
      treated with RT and three cycles of ICT if T4 or >N1; finally, 125 patients with
      non-surgical tumours of any localisation treated with four cycles of induction CT
      and RT. RESULTS: LARYNX: Actuarial local control (LC), disease-free survival
      (DFS) and overall survival (OS) at 5 years were 78, 73 and 48%, respectively, in
      T2 tumours and 75, 72 and 60% in stage III disease. HYPOPHARYNX: Actuarial LC,
      DFS and OS at 4 years were 44, 39 and 35%, respectively. OROPHARYNX: Actuarial
      LC, DFS and OS at 5 years were 52, 44 and 31%, respectively. NASOPHARYNX:
      Actuarial LC, DFS and OS at 5 years were 78, 72 and 78%, respectively. NON
      SURGICAL TUMORS: Actuarial LC, DFS and OS at 5 years were 39, 33 and 19%,
      respectively. A total of 47 patients (14.8%) of the overall group had a second
      tumour, 72% of them tobacco-related. Only patients with nasopharynx tumours had a
      low incidence of second tumours. CONCLUSIONS: Twice-a-day external RT can be
      effectively managed in patients with head and neck cancer. Second neoplasm and
      intercurrent diseases become an important problem in low and medium stages
      whereas disease recurrences is the main problem in advanced stages. Results by
      localisation permit to obtain conclusions about their indications in each one.

PMID- 12208571
TI  - A randomized, double-blind, placebo-controlled trial of concomitant pilocarpine
      with head and neck irradiation for prevention of radiation-induced xerostomia.
AB  - BACKGROUND: Xerostomia is one of the disturbing side-effects of radiotherapy to
      the head and neck region. Pilocarpine has been approved for the treatment of this
      condition in the chronic phase, but its use concurrent with radiation could also
      be beneficial for prevention or reduction of the subsequent radiation-induced
      xerostomia. We undertook to test this hypothesis in a clinical trial. METHODS: At
      the start of radiotherapy, randomization was performed to either pilocarpine 5 mg
      three times daily or placebo in a double-blind setting. The drug was started with
      irradiation and continued until 3 months after the end of radiotherapy.
      Xerostomia was evaluated 6 months after the end of radiation by a subjective
      visual analog scale questionnaire. Also the objective grade of xerostomia was
      recorded by two separate observers. RESULTS: A total number of 60 patients were
      randomized into the trial, but unfortunately only 39 patients were finally
      evaluated for xerostomia, 18 in the pilocarpine and 21 in the placebo group. Mean
      age was 42 years, and mean parotid dose was 58 Gy. Mean subjective xerostomia was
      40.3 mm in the pilocarpine group and 57 mm in the placebo group (P = 0.02). Also
      mean objective xerostomia grade was 2.2 in the pilocarpine group and 2.6 in the
      placebo group (P = 0.01). Subjective and objective xerostomia results were
      positively correlated (P = 0.01). Age and the parotid dose did not have a
      significant effect on xerostomia. CONCLUSIONS: Compared to placebo, pilocarpine
      used with radiotherapy could lead to a significant diminishment of subsequent
      radiation-induced xerostomia.

PMID- 12208572
TI  - Dose-intensified accelerated vindesine-ifosfamide-cisplatin (VIP) chemotherapy
      followed by high-dose accelerated hyperfractionated radiotherapy in patients with
      pathologically proven stage IIIB non-small cell lung cancer: a feasibility study.
AB  - This study shows the feasibility of accelerated vindesine-ifosfamide-cisplatin
      chemotherapy, immediately followed by intensive radiotherapy to the residual
      tumour in responding patients, in 16 patients with pathologically proven stage
      IIIB non-small lung cancer. All toxicities were reversible, with only two of ten
      patients experiencing grade 3 oesophagitis, no treatment-related deaths and no
      serious late effects.

PMID- 12208573
TI  - Declining hemoglobin during chemoradiotherapy for locally advanced non-small cell
      lung cancer is significant.
AB  - BACKGROUND AND PURPOSE: Tumor hypoxia and anemia have been linked to poor overall
      survival and local control in carcinomas of both the uterine cervix and the head
      and neck for patients undergoing radiotherapy. Little is known about the effect
      of these factors on the outcome of NSCLC patients with locally advanced disease
      undergoing chemoradiation therapy. MATERIALS AND METHODS: To examine the impact
      of anemia in stage III NSCLC patients undergoing combined modality therapy, we
      reviewed our database from three sequential trials of concurrent weekly
      paclitaxel +/- carboplatin and radiation therapy. 115 pts from 17 institutions
      were enrolled from 4/94 to 5/97. In this series, hemoglobin values were collected
      before treatment and weekly during radiotherapy. We correlated baseline Hb and Hb
      changes during chemoradiation treatment with overall survival. RESULTS: Although
      pretreatment anemia was common (30% Hb = 110-130 g/l, 16% Hb <110 g/l), log-rank
      analyses of presenting Hb, average Hb and minimum Hb during treatment were not
      statistically significantly predictive of survival. However in a Cox model,
      declining hemoglobin during chemoradiation had a statistically significant impact
      on survival. CONCLUSIONS: These analyses reveal that a decline in hemoglobin
      during chemoradiation for stage III NSCLC has a statistically significant
      correlation with overall survival. Strategies maximizing hemoglobin during
      combined modality therapy need further exploration in well-planned randomized
      trials.

PMID- 12208574
TI  - Combined external and intraluminal radiotherapy in the treatment of advanced
      oesophageal cancer.
AB  - BACKGROUND AND PURPOSE: Oesophageal cancer still has a dismal prognosis. Radical
      surgery is by far the most successful treatment but most patients are not
      operable at the time of diagnosis and for these patients external beam
      radiotherapy with or without concurrent chemotherapy offers the best choice for
      cure or palliation. In patients with advanced oesophageal cancer, intraluminal
      brachytherapy has been proposed as a complementary method to increase local
      control. PATIENTS AND METHODS: Between 1989 and 1999, 40 patients with inoperable
      oesophageal cancer were treated with combined external and intraluminal radiation
      therapy in Turku University Central Hospital. The external radiation was
      performed with a median total dose of 40 Gy given in 20 fractions. On the average
      a week after the external radiation a median total dose of 10 Gy intraluminal
      radiation therapy was given in 4 fractions. RESULTS: The intraluminal
      brachytherapy could be performed without technical difficulties and no major
      complications were seen. In many cases (16 out of 40 patients, 40%), the symptoms
      could be relieved immediately and in most cases the progression of the disease
      could be delayed as evidenced by post-treatment serial endoscopy. No major
      complications were encountered. The 1- and 2-year survival rates were 30 and
      17.5%, respectively. All patients alive at 2 years can be considered as long-term
      survivors. Median follow-up was 86 months. CONCLUSIONS: Intraluminal
      brachytherapy is a safe and efficient treatment modality which offers a potential
      means of cure for selected patients with oesophageal cancer.

PMID- 12208575
TI  - Intraoperative radiation therapy for patients with recurrent rectal and sigmoid
      colon cancer in previously irradiated fields.
AB  - A retrospective study evaluated 15 patients with pelvic recurrence of colorectal
      cancer in a previously irradiated region who received intraoperative radiation
      therapy (IORT) as part of salvage therapy. Total prior external beam radiation
      therapy (EBRT) doses ranged from 45 to 79.2 Gy. Tumor resection was accomplished
      in 14 patients, with an exenteration performed in seven. IORT dose was 15-20 Gy.
      Three patients received additional EBRT as a post-operative course of 25.2 Gy in
      14 fractions. Actuarial 3-year local control rate was 25%. The 3-year overall
      survival rate was 29%. Patients with fixed and/or bulky pelvic tumors had a local
      control rate of 19% at 12 months and median overall survival of 9 months.
      Patients with less extensive clinical presentations of anastomotic non-fixed
      transmural recurrence, isolated pelvic node metastasis and rectal recurrence
      following local excision had a local control rate of 42% at 36 months and median
      survival of 43 months. We conclude that clinical presentation of recurrent
      disease is an important prognostic factor. The value of IORT may be limited to
      patients with less extensive clinical presentations.

PMID- 12208576
TI  - Detection of defects in myocardial perfusion imaging in patients with early
      breast cancer treated with radiotherapy.
AB  - BACKGROUND AND PURPOSE: To evaluate radiation-induced defects in myocardial
      perfusion imaging in early breast cancer patients treated with modern technique
      radiotherapy. PATIENTS AND METHODS: Twenty-four patients with left-breast tumours
      and 12 control patients with right-breast tumours, relapse-free since treatment
      for primary disease, who had undergone radiotherapy at least 5 years previously
      and with no history of ischaemic heart disease prior to radiotherapy underwent
      study. In left-breast patients, at least 1 cm of heart was required to have been
      in the treatment field. Patients underwent cardiac assessment and single photon
      emission computerized tomography myocardial perfusion imaging. RESULTS:
      Myocardial perfusion tracer uptake was abnormal in 17 (70.8%) left-breast and two
      (16.7%) right-breast patients (P = 0.002). Of the 17 abnormal scans in left
      breast patients, abnormalities were confined to the cardiac apex in 16 patients,
      and perfusion defects were reversible (n = 7), fixed (n = 7) or mixed (n = 3).
      Reversible perfusion defects that were not confined to the cardiac apex were
      observed in two right-breast patients. Left ventricular ejection fraction was
      normal in all 33 patients in whom it was measured, and no myocardial perfusion
      abnormalities were judged to require treatment or follow-up. CONCLUSIONS: In this
      selected study population modern technique radiotherapy to the left breast was
      associated with a significantly greater number of myocardial perfusion
      abnormalities than radiotherapy to the right breast. These abnormalities were
      both reversible and irreversible, suggesting that radiotherapy can lead to both
      myocardial damage and to epicardial coronary disease. With a minimum of 5 years
      follow-up since treatment, no abnormalities were considered to be clinically
      significant.

PMID- 12208577
TI  - Quality assurance of the EORTC trial 22911. A phase III study of post-operative
      external radiotherapy in pathological stage T3N0 prostatic carcinoma: the dummy
      run.
AB  - INTRODUCTION: A dry run of a clinical trial (EORTC 22911) is presented in which
      12 centres have participated. These are the centres which have contributed the
      largest number of patients to the trial. MATERIAL AND METHODS: Each participating
      centre received data from a suitable patient. Investigators were asked to plan
      and 'treat' the patient according to the protocol guidelines and return the data
      for evaluation of compliance. RESULTS: The results show that compliance to the
      protocol guidelines was generally good. There were a few minor deviations in the
      dose and fractionation schedule, in the volume reduction for the booster dose and
      in the dose prescription point. None of these deviations will affect the outcome
      of the study. The most important observation is the large inter-centre variation
      in target volumes. CONCLUSIONS: The results of this study underlines the need for
      a strict definition of the target volume and the adoption of the ICRU 50
      recommendations in future protocols.

PMID- 12208578
TI  - Geometrical uncertainties, radiotherapy planning margins, and the ICRU-62 report.
AB  - In this paper, we elaborate on the proposals in the ICRU-62 report concerning
      planning target volume (PTV) margins for geometrical uncertainties during
      radiotherapy, such as variations in patient set-up and internal organ motion.
      According to the ICRU, these margins should be such that the planned dose in the
      PTV is representative of the real dose in the 'moving' clinical target volume
      (CTV). We demonstrate that the dosimetrical consequences of systematic and random
      geometrical uncertainties are fundamentally different, which should be reflected
      in margin calculations. The recommendation in the ICRU-62 report, to
      quadratically add standard deviations for systematic (Sigma(tot)) and random
      (sigma(tot)) errors to determine an overall standard deviation for margin
      calculations, is therefore generally not valid. Instead, a previously published
      recipe for PTV margin calculation, M = 2Sigma(tot) + 0.7sigma(tot), does indeed
      account for the different impact of systematic and random errors on the dose in
      the CTV. If, for both random and systematic uncertainties, the internal and
      external errors are uncorrelated and quantified by the standard deviations
      sigma(int), sigma(ext), Sigma(int), Sigma(ext), then Sigma(tot) = square root
      (Sigma(int)(2) + Sigma(ext)(2)) and sigma(tot) = square root (sigma(int)(2) +
      sigma(ext)(2)). If the PTV margin thus acquired is deliberately reduced to spare
      normal tissues, the planned PTV dose is not representative of the CTV anymore.
      Therefore, we recommend to also report the minimum dose in the volume originally
      defined by the recipe (designated RTV, i.e. representative target volume).

PMID- 12208579
TI  - Evaluation of dose calculation algorithms for dynamic arc treatments of head and
      neck tumors.
AB  - BACKGROUND AND PURPOSE: To investigate if the Pencil Beam (PB) algorithm takes
      the disturbance of the dose distribution due to tissue inhomogeneities
      sufficiently into account in dynamic field shaping rotation therapy (called the
      dynamic arc treatment modality) for fractionated stereotactic radiation therapy
      of head and neck tumors. MATERIAL AND METHODS: A treatment plan using the dynamic
      arc treatment modality of an oropharynx lesion on a humanoid phantom was
      evaluated. The same plan was calculated with three different calculation
      algorithms: the Clarkson and the PB algorithm (both available on the planning
      system of the Novalis system used for dynamic arc treatments), and the Collapsed
      Cone Convolution Superposition (CC) algorithm (used by the Pinnacle planning
      system). The three resulting plans are compared using isodose distributions and
      cumulative dose volume histograms (CDVHs). An intercomparison of the results of
      the three algorithms was performed to investigate how accurately each of them
      takes the influence of tissue inhomogeneities into account such as bony
      structures and air cavities often appearing in the head and neck region.
      Additionally, the resulting plans were compared with absolute and relative
      dosimetric measurements of the treatment plan on the humanoid phantom with
      thermoluminescent detectors and radiographic film, respectively. RESULTS: All
      calculated dose distributions show a good agreement with the measured
      distribution except in the planning target volume (PTV) in and at the border of
      the air cavity. All three algorithms overestimate the dose in the PTV at the
      boundary with the low-density tissue, with 12, 10 and 7% for the Clarkson, the PB
      and the CC algorithm, respectively. The correspondence between the calculated
      dose distributions is reflected in the graphs of the CDVHs. They show similar
      curves for the PTV and the structures except for the left parotic gland and the
      myelum. CONCLUSIONS: The PB algorithm of the Novalis system calculates a
      treatment plan for the dynamic arc treatment modality adequately for fractionated
      stereotactic radiation therapy of head and neck tumors, except in the PTV in and
      at the border of the air cavity where the actual dose is overestimated. Care
      needs to be taken in clinical cases where it is critical to irradiate the air
      tissue boundary to a sufficient dose.

PMID- 12208580
TI  - Verification of the dose to the isocentre in stereotactic plans.
AB  - BACKGROUND AND PURPOSE: The aim of the study was: (a) to develop a simple,
      reproducible, technique to verify the dose to the isocentre, in a typical
      stereotactic treatment plan, for collimators from 12.5 to 40 mm in diameter; (b)
      to investigate a variety of detectors to compare different approaches; and (c) to
      introduce the technique into a quality assurance programme. MATERIAL AND METHODS:
      The symmetry, directional response and stability of calibration of a small 0.125
      cm(3) ion chamber, a diamond and three types of diode (photon, electron and
      stereotactic) were tested. Correction factors were calculated to account for
      directional dependence, where appropriate and calibration factors were obtained
      to convert each reading to absorbed dose in water. Single arcs and typical four
      arc treatments were planned on XKnife and the dose to the isocentre verified in
      phantom with each usable detector. RESULTS: The ion chamber showed no asymmetry,
      the stereotactic diodes exhibited 4% and the others 1-2%. Maximum directional
      dependence was 1% for the ion chamber and diamond and 7-20% for the diodes.
      Correction factors were calculated to account for this. Only the response of the
      diodes decreased with cumulative dose; the response of the other detectors
      remained constant. The ion chamber, electron diode and diamond measured the dose
      in single arcs to within 1.5% of calculation, in the 40 and 12.5 mm collimators.
      The photon diode was within 3.5 and 2.5% in the largest and smallest collimators,
      respectively. CONCLUSION: A simple method of verification was developed. The ion
      chamber, the diamond and the electron diode were found to be the best detectors
      to verify the dose to the isocentre in a typical multiple arc treatment for
      collimators between 40 and 12.5 mm in diameter. The technique has been
      incorporated into a quality assurance programme, using the ion chamber and
      diamond, on a twice yearly basis.

PMID- 12208581
TI  - Theoretical simulation of oxygen tension measurement in the tissue using a
      microelectrode: II. Simulated measurements in tissues.
AB  - BACKGROUND AND PURPOSE: The objectives of this study were to make a computer
      simulation of tissues with different vascular structures and to simulate
      measurements of oxygen tension using an Eppendorf-like electrode in these tissues
      and to compare the response to radiation of the tissues with the real oxygen
      distributions (called input distribution) with the response to radiation of the
      tissues in which the oxygen distribution is given by the results of the simulated
      measurements (called output distribution). MATERIALS AND METHODS: The structure
      of various tissues and the measurements of oxygen tension using a microelectrode
      were simulated using a computer program. The mathematical model used combines the
      description of a gradient of tissue oxygenation and the electrode absorption
      process. RESULTS: We have compared the oxygen distributions resulting from
      diffusion (input) with those obtained from a simulation of measurements (output)
      for various tissues in the same points. Because the electrode measurement is an
      averaging process, the calculated oxygen distributions are different from the
      expected ones and the extreme high and low values are not detected. We have then
      calculated the survival curves describing the response to radiation if there is a
      small fraction of truly hypoxic cells (expected values) or a large fraction of
      cells at intermediate values (observed results) in order to determine the
      differences between them. CONCLUSIONS: The results of our study show that oxygen
      electrode measurements do not give the true distribution of pO(2) values in the
      tissue. However, our results do not contradict the numerous empirical
      correlations between the Eppendorf measurements of tumour oxygenation and the
      outcome of treatments. Measurement results will be misleading for modelling
      purposes since they do not reflect the actual distributions of oxygen tensions in
      the measured tissue. Decisions based on such modelling could be very dangerous,
      especially with respect to the clinical response of tumours to new treatments.

PMID- 12208582
TI  - Radiation induced myelopathy following treatment for metastatic spinal cord
      compression.

PMID- 12208583
TI  - Do results of the ENABLE (Endothelin Antagonist Bosentan for Lowering Cardiac
      Events in Heart Failure) study spell the end for non-selective endothelin
      antagonism in heart failure?
AB  - The last two decades have seen major advances in the treatment of chronic heart
      failure, primarily as a result of therapeutic manipulation of activated
      neurohormonal systems. Despite this progress, many patients still suffer
      significant morbidity and premature death. Antagonism of the biological effects
      of endothelin, a potent vasoconstrictor, represents a further potential target.
      To date, positive results from animal models of heart failure have not been
      translated into clinical practice, perhaps as a consequence of the high doses of
      drug used. The ENABLE (Endothelin Antagonist Bosentan for Lowering Cardiac Events
      in Heart Failure) study evaluated the effects of low dose bosentan, a non
      selective endothelin receptor antagonist, in patients with severe heart failure
      (left ventricular ejection fraction <35%, New York Heart Association class IIIb
      IV). A total of 1,613 patients were randomized to receive either bosentan (125 mg
      twice a day) or placebo. The preliminary results were presented at the 51st
      Annual Scientific Session of the American College of Cardiology (17-20 March
      2002, Atlanta, GA, USA). The primary endpoint of all-cause mortality or
      hospitalization for heart failure was reached in 321/808 patients on placebo and
      312/805 receiving bosentan. Treatment with bosentan appeared to confer an early
      risk of worsening heart failure necessitating hospitalization, as a consequence
      of fluid retention. It has been suggested that further studies using even lower
      doses of bosentan or more aggressive concomitant diuretic therapy may avoid this
      adverse effect. The results from the ENABLE study have, however, thrown further
      doubt on the potential benefits of non-specific endothelin receptor blockade in
      heart failure.

PMID- 12208584
TI  - DANAMI-2: is primary angioplasty superior to thrombolysis in acute MI when the
      patient has to be transferred to an invasive centre?
AB  - Primary angioplasty is superior to thrombolysis in acute myocardial infarction
      when performed in a timely manner but the benefits are unknown when inter
      hospital transfer is required for angioplasty. On the 20th March 2002 at the
      American College of Cardiology 51st Annual Scientific Session, the results of the
      Danish Multicentre Randomized Trial on Thrombolytic Therapy versus Acute Coronary
      Angioplasty in Acute Myocardial Infarction (DANAMI-2) were presented. 1,572
      patients were randomized to front loaded tPA or angioplasty on presentation
      within 12 h of acute myocardial infarction; 1,129 from hospitals requiring
      transfer for up to 3 h for angioplasty. The trial was stopped early since there
      was a 40% relative reduction in the composite primary end-point of death,
      disabling stroke or reinfarction within 30 days (absolute reduction 13.7 to 8%,
      p=0.0003) with primary angioplasty. This appeared to be driven by a significant
      reduction of reinfarction from 6.3 to 1.6%. Ambulance transfer was shown to be
      safe but time to angioplasty was approximately 60 min longer than time to
      thrombolysis. No data are as yet available on the relative infarct sizes or left
      ventricular function in the two groups. The management of acute myocardial
      infarction is an area of missed opportunities. Patients present late to hospital,
      up to 30% of eligible patients do not receive reperfusion therapy and door to
      needle time is longer than is ideal. Whilst we await the full details of the
      trial and long term follow-up, we should not forget the challenges of
      conventional management of acute myocardial infarction.

PMID- 12208585
TI  - Use of cardiovascular medications in the elderly.
AB  - Cardiovascular disease is the leading cause of death in patients aged 65 and
      above. Although elderly persons represent only 12.4% of the US population, they
      account for about a third of drug expenditures. However the appropriate use of
      cardiovascular medications in these patients has been shown to reduce the rate of
      cardiovascular morbidity and mortality. The normal aging and the disease process
      in the elderly result in significant changes at the structural and molecular
      level in the elderly. The changes that take place in the autonomic nervous
      system, the kidneys, and the liver in the elderly modify the metabolism and
      clinical effects of most medications. Elderly patients are also susceptible to
      side effects and adverse drug reactions. Physicians should have a clear
      understanding of the normal aging processes, the abnormal changes due to disease
      process and the changes in the pharmacology of drugs in the elderly to deliver
      proper care to the elderly patient.

PMID- 12208586
TI  - QT dispersion measured by an automatic continuous method early in patients
      admitted for chest pain.
AB  - BACKGROUND: There is a need for risk markers in patients with acute chest pain.
      QT dispersion (QTd) is a prognostic marker in several groups of patients. A
      problem with the manual measurement of QTd is operator dependency. This can be
      avoided by using an automatic method. We investigated QTd, derived from multiple
      automatic measurements, as a risk marker in a population with chest pain.
      METHODS: In 548 patients admitted to the coronary care unit for chest pain and
      nondiagnostic ECG, 12-lead ECG recordings were collected each minute during the
      initial 17 h. From recordings with > or =10 valid leads, mean QTd (QTdMean), QTd
      in the first satisfactory recording and estimates of variability of QTd were
      computed and correlated to outcome. RESULTS: In the group with QTdMean > or =40
      ms (n=277), 10 patients died during the initial 30 days; one patient died in the
      group with QTdMean <40 ms (n=271) (P=0.07). During follow-up (median 6 months),
      19 vs. five patients died in each group (P=0.03). The figures for the triple
      endpoint death/myocardial infarction/revascularisation were 52 vs. 27 events
      during the initial 30 days (P=0.018) and 76 vs. 41 events during follow-up
      (P=0.003). QTd in the first recording did not predict new cardiac events.
      CONCLUSIONS: QTd measured as the mean value of multiple recordings was found to
      be a powerful marker for cardiac events during follow-up. It was superior to the
      analysis of QTd in a single ECG. It can be used for the selection of low-risk
      patients, but was not effective in identifying high-risk patients.

PMID- 12208588
TI  - Use of medical resources, complications and long-term outcome in patients
      hospitalized with acute chest pain. A comparison between a city university
      hospital and a county hospital.
AB  - OBJECTIVE: The primary aim was to test the hypothesis that there is a difference
      in long-term outcome after hospital discharge among patients hospitalized with
      acute chest pain in a university hospital and a county hospital. Secondary aims
      were to compare these two hospitals with regard to use of medical resources,
      occurrence of complications and risk indicators for death. PATIENTS: All patients
      hospitalized at Sahlgrenska University Hospital in Goteborg (with a catchment
      population of 706 inhabitants/km(2)) and Uddevalla County Hospital (with a
      catchment population of 34 inhabitants/km(2)) due to symptoms of acute chest pain
      during a period of 6 months. RESULTS: Complications, use of medical resources and
      mortality during the subsequent 2 years after discharge were compared among 1,592
      hospitalizations in a city hospital and 822 in a county hospital due to acute
      chest pain. Angina pectoris after the first event, congestive heart failure and
      various arrhythmias were more frequently reported in the county hospital. The use
      of medical resources differed. Thus, the use of betablockers, heparin,
      antiarrhythmics, diuretics and nipride was more frequent in the county hospital,
      whereas the use of nitrates, digitalis, coronary angiography, percutaneous
      transluminal coronary angioplasty (PTCA) and coronary artery bypass grafting
      (CABG) was more frequent in the city hospital. Despite these differences, the
      mortality 2 years after hospital discharge was similar (14.7% in the city
      hospital and 12.8% in the county hospital, P=0.26). Two factors, intravenous
      digitalis in hospital and a prescription of insulin at discharge, were
      significantly more associated with death in the county hospital compared with the
      city hospital. CONCLUSIONS: When comparing a city university hospital with a
      county hospital with regard to patients admitted with chest pain, major
      differences in terms of complications and use of medical resources were found.
      Thus, various complications were reported more frequently in the county hospital.
      The use of medical resources varied, some being used more frequently in the
      county hospital, whereas others were used more frequently in the university
      hospital. Despite these differences the mortality 2 years after hospital
      discharge was similar in the two cohorts.

PMID- 12208590
TI  - Release of cardiac troponin I after temporally graded acute coronary ischaemia
      with electrocardiographic ST depression.
AB  - BACKGROUND: Elevation of cardiac biochemical markers and ST segment depression in
      the electrocardiogram have important roles in the risk stratification of unstable
      coronary syndromes. We assessed graded duration of acute coronary ischaemia with
      ST depression versus release of cardiac troponin I (cTnI) and conventional
      cardiac markers in 15 ischaemic pigs and 11 controls. METHODS: Coronary ischaemia
      was induced via percutaneous technique by semiinflating an angioplasty balloon in
      the left circumflex artery. Blood velocity monitored by Doppler was reduced until
      ST depression > or =0.1 mV was obtained. Among 26 pigs, six controls had jugular
      vein sheath introduced only, five controls jugular vein and bilateral femoral
      sheaths, and 15 pigs were divided into three equal groups (n=5) in which
      ischaemia was maintained for 10, 20 and 30 min, respectively. RESULTS: Mean blood
      flow velocity (cm/s) at baseline was 16.3+/-6.5 and was reduced to 4.1+/-3.2 (25%
      of normal, range 20-29%) during ischaemia. cTnI (microg/l) did not increase in
      controls but increased from 0.05 to 0.52 (P<0.05) and 0.76 (P<0.05) with 10 and
      20 min of ischaemia, and to 30.77 (P<0.05) with 30 min of ischaemia. A rise of
      myoglobin and conventional cardiac enzymes did not distinguish controls with
      arterial cut-down from the ischaemia groups. CONCLUSION: Release of cTnI depends
      on the duration of ST depression ischaemia. The critical time for a major release
      seems to be between 20 and 30 min. Thus, very early intervention in patients with
      prolonged ST depression ischemia should be focused on in future clinical trials.

PMID- 12208592
TI  - Effects of metoprolol in chagasic patients with severe congestive heart failure.
AB  - BACKGROUND: Beta-blockers are the most effective and promising treatment for
      congestive heart failure secondary to left ventricular dysfunction and
      sympathetic activation. METHODS: Since chagasic patients with severe congestive
      heart failure have left ventricular systolic dysfunction and neurohormonal
      activation, we administered metoprolol to nine chagasic patients who were in
      severe congestive heart failure. Metoprolol (5 mg p.o. daily) was uptitrated on a
      weekly basis. RESULTS: Patients were receiving digitalis, diuretics and
      angiotensin converting enzyme inhibitors and had left ventricular dilatation
      (6.77+/-0.89 cm), depressed ejection fraction (0.20+/-0.06), low systolic blood
      pressure (93+/-11 mm Hg), sinus tachycardia (115+/-17 beats/min) and sympathetic
      activation 400+/-246 pg/ml). One patient was in New York Heart Association
      Functional class III and eight patients were in functional class IV. At the end
      of the fifth week of treatment (metoprolol 25 mg), seven patients were in
      functional class III and two were in functional class II. Heart rate decreased to
      85+/-15 beats/min (P<0.05) and the systolic blood pressure increased to 108+/-18
      mm Hg (P<0.01). There were no significant changes in left ventricular ejection
      fraction. By the end of the tenth week of treatment (metoprolol 50 mg), four
      patients were now in functional class I and five were in functional class II.
      Left ventricular ejection fraction increased to 0.27+/-0.05 (P<0.01) and the left
      ventricular systolic diameter decreased from 6.38+/-0.90 at baseline to 5.89+/
      0.59 and 5.76+/-0.96 after 25 and 50 mg of metoprolol treatment, respectively
      (P<0.04). Plasma norepinephrine decreased non-significantly to 288+/-91 pg/ml.
      CONCLUSION: Beta-blockers improve the clinical status and the left ventricular
      function of chagasic patients with severe congestive heart failure.

PMID- 12208593
TI  - Safety and efficacy of valsartan versus enalapril in heart failure patients.
AB  - Although a cornerstone in the treatment of heart failure, angiotensin-converting
      enzyme inhibitors are under-used, partly due to side effects. If proven at least
      similarly efficacious to angiotensin-converting enzyme inhibitors, angiotensin
      receptor blockers may replace them due to their superior tolerability. We aimed
      to compare the efficacy and safety of valsartan and enalapril in heart failure
      patients stabilised on an angiotensin-converting enzyme inhibitor. We randomised
      141 patients (mean 68 years, 74% males) with stable mild/moderate heart failure
      and left ventricular ejection fraction 0.45 or less, to valsartan 160 mg q.d.
      (n=70) or enalapril 10 mg b.i.d. (n=71) for 12 weeks. Changes in 6-min-walk test
      (primary efficacy variable), patients' wellbeing and left ventricular size and
      function did not differ significantly between the treatment groups. Valsartan was
      significantly non-inferior to enalapril in walk test distance change: least
      square means treatment difference +1.12 m (95% confidence interval -21.9 to
      24.1), non-inferiority P<0.001. Left ventricular size (P<0.001) and function
      (P=0.048) improved significantly only in the valsartan group. Fewer patients
      experienced adverse events in the valsartan group (50%) than in the enalapril
      group (63%), although statistically non-significant. Valsartan is similarly
      efficacious and safe to enalapril in patients with stable, mild/moderate heart
      failure, previously stabilised on an angiotensin-converting enzyme inhibitor and
      directly switched to study medication.

PMID- 12208594
TI  - Spontaneous echo contrast in the descending aorta in patients without aortic
      dissection: associated clinical and echocardiographic characteristics.
AB  - OBJECTIVE: To evaluate the frequency, clinical and echocardiographic correlates
      of spontaneous echo contrast in the descending aorta in the absence of
      dissection. METHODS: Prevalence of spontaneous echo contrast in the descending
      aorta in the absence of dissection, and its clinical and echocardiographic
      correlates were investigated in 1,199 consecutive patients who underwent
      transesophageal echocardiography. RESULTS: Spontaneous echo contrast in the
      descending aorta was detected in 54 (4.5%) patients. Patients with spontaneous
      echo contrast in the descending aorta had an older age (60.6+/-8 vs. 40.6+/-14.2
      years, p=0.0001), an increased prevalence of male gender (66.7 vs. 43.9%,
      p=0.001), an increased diameter of ascending aorta (4.2+/-1.0 vs. 3.3+/-1.1 cm,
      p=0.0001), an increased diameter of descending aorta (3.1+/-0.9 vs. 2.1+/-0.4 cm,
      p=0.0001), a higher prevalence of aortic wall calcification (9.3 vs. 0.5%,
      p=0.00001), complex plaque in the descending aorta (13 vs. 0.7%, p=0.0001), left
      ventricular dysfunction (7.4 vs. 2.1%, p<0.05), a lower incidence of severe
      aortic regurgitation (0 vs. 3.5%, p<0.05), a lower peak flow velocity in the
      descending aorta (28+/-9 vs. 51+/-21 cm/s, p<0.00001), and a lower maximal shear
      rate in the descending aorta (51+/-29 vs. 105+/-47 s(-1), p<0.00001) compared
      with patients without spontaneous echo contrast in the descending aorta. However,
      prevalence of atrial fibrillation, mitral valve disease, intracardiac spontaneous
      echo contrast and/or thrombus and embolic event were not different between
      patients with and without spontaneous echo contrast in the descending aorta
      (p>0.05). Shear rate, diameter of the descending aorta, aortic wall
      calcification, complex plaque in the descending aorta, absence of severe aortic
      regurgitation and male gender were independent variables of spontaneous echo
      contrast in the descending aorta. CONCLUSIONS: Spontaneous echo contrast in the
      descending aorta is a local and flow dependent phenomenon relates to aortic
      dilation, atherosclerosis, and decreased shear rates in the descending aorta.
      However, in this study, spontaneous echo contrast in the descending aorta was not
      found to be associated with embolic events.

PMID- 12208595
TI  - Plasma concentrations of fibrinolytic factors in the subacute phase of myocardial
      infarction predict recurrent myocardial infarction or sudden cardiac death.
AB  - BACKGROUND: The prognostic value of plasma concentrations of tissue type
      plasminogen activator (t-PA), plasminogen activator inhibitor-1 (PAI-1), and C
      reactive protein has been reported in patients with coronary artery disease.
      However, the association between cardiac events and these factors during the
      acute and subacute phases of myocardial infarction (MI) is unknown. The purpose
      of this study was to determine whether elevated plasma concentrations of t-PA,
      PAI-1, and C-reactive protein in patients with MI are associated with future
      recurrent MI or sudden cardiac death. METHODS: We studied 106 consecutive
      patients who survived a confirmed first MI between 1993 and 1998 in our hospital.
      The control group consisted of 50 patients who had no significant coronary artery
      stenosis. Blood samples were obtained at the time of admission for acute MI and
      on the 28th day after admission. Patients were followed for a mean of 50 months
      after these measurements. The primary end points were sudden cardiac death and
      fatal or nonfatal acute MI. RESULTS: Of the 92 patients who were available for
      follow-up, 10 had cardiac events. Both the plasma t-PA and PAI-1 concentrations
      were elevated on day 1 of acute MI compared to the control group and decreased by
      day 28, but remained higher than those in the controls. Plasma C-reactive protein
      concentration was also elevated on day 1 and decreased by day 28. Using a
      stepwise variable choice model of Cox proportional hazards analysis including
      these fibrinolytic factors and C-reactive protein, only the t-PA concentration in
      the subacute phase was a significant predictor of cardiac events (relative risk
      per S.D. 3.20, P<0.01). We further found that independent of other risk factors,
      an elevated t-PA concentration was predictive of cardiac events. CONCLUSIONS:
      This study reveals that a rise in endogenous t-PA concentration during the
      subacute phase of MI could predict recurrent MI or sudden cardiac death.

PMID- 12208597
TI  - Prolonged pleural effusion following Fontan operation: effective pleurodesis with
      talc slurry.
AB  - Prolonged pleural effusions following a Fontan operation are a difficult problem.
      Although fenestrations and embolizations of systemic-pulmonary artery collaterals
      were suggested to treat and to decrease the risk of this complication, talc
      slurry pleurodesis may successfully augment and accelerate the beneficial effects
      of those techniques against the resistant effusions.

PMID- 12208596
TI  - Influence of age on clinical course, management and mortality of acute myocardial
      infarction in the Spanish population.
AB  - BACKGROUND: To assess age-related differences in cardiovascular risk factors,
      clinical course and management of patients with acute myocardial infarction (AMI)
      in intensive care (ICU) or coronary care units (CCU). METHODS: A retrospective
      cohort study was conducted of all AMI patients listed in the ARIAM register
      (Analysis of Delay in AMI), a multi-centre register in which 119 Spanish
      hospitals participated. The study period was from January 1995 to January 2001. A
      univariate analysis was carried out to evaluate differences between different age
      groups. Multivariate analysis was used to assess whether age difference was an
      independent predisposing factor for mortality and for differences in patient
      management. RESULTS: 17,761 patients were admitted to the ICUs/CCUs with a
      diagnosis of AMI. The distribution by ages was: <55 years, 3,954 patients
      (22.3%); 55-64 years, 3,593 (22.2%); 65-74 years, 5,924 (33.4%); 75-84 years,
      3,686 (20.8%); and >84 years, 604 (3.4%) (P<0.0001); 24.6% of the patients were
      female, and the relative proportion of females increased with age. There were
      clear differences in risk factors between the different age groups, with a
      predominance of tobacco, cholesterol and family history of heart disease in the
      younger patients. The incidence of complications, including haemorrhagic
      complications, increased significantly with age. The older age groups had a lower
      rate of thrombolysis and less use of revascularisation techniques. The mortality
      of the above groups was 2.6, 5.4, 10.7, 17.7 and 25.8%, respectively. Age
      difference was an independent predictive variable for mortality and the
      administration of thrombolysis. CONCLUSIONS: The distinct age groups differed in
      cardiovascular risk factors, management and mortality. Age is a significant
      independent predictive variable for mortality and for the administration of
      thrombolysis.

PMID- 12208598
TI  - Extrinsic left atrial compression in a patient with achalasia.
AB  - Left atrial compression by the esophagus, the stomach, or both is an uncommon but
      important cause of hemodynamic compromise. Achalasia is a disease of the
      esophagus with dilatation of the distal part and constriction of the lower
      oesophageal sphincter. Dilated esophagus is a rare cause of left atrial
      compression. Timely and precise diagnosis is of paramount importance in cases of
      left atrial compression and echocardiography enables clinicians to make a
      differential diagnosis successfully in most cases. Correction of primary
      pathology will usually lead to the return of normal hemodynamic function. We
      describe a case of extrinsic left atrial compression caused by the dilated
      esophagus due to achalasia that caused paroxysms of atrial tachycardia and
      hemodynamic compromise.

PMID- 12208599
TI  - Detection of Takayasu arteritis in early stage by computed tomography.

PMID- 12208600
TI  - Effects of chromium on the immune system.
AB  - Chromium is a naturally occurring heavy metal found commonly in the environment
      in trivalent, Cr(III), and hexavalent, Cr(VI), forms. Cr(VI) compounds have been
      declared as a potent occupational carcinogen among workers in chrome plating,
      stainless steel, and pigment industries. The reduction of Cr(VI) to Cr(III)
      results in the formation of reactive intermediates that together with oxidative
      stress oxidative tissue damage and a cascade of cellular events including
      modulation of apoptosis regulatory gene p53, contribute to the cytotoxicity,
      genotoxicity and carcinogenicity of Cr(VI)-containing compounds. On the other
      hand, chromium is an essential nutrient required to promote the action of insulin
      in body tissues so that the body can use sugars, proteins and fats. Chromium is
      of significant importance in altering the immune response by immunostimulatory or
      immunosuppressive processes as shown by its effects on T and B lymphocytes,
      macrophages, cytokine production and the immune response that may induce
      hypersensitivity reactions. This review gives an overview of the effects of
      chromium on the immune system of the body.

PMID- 12208601
TI  - Analysis of Neisseria lactamica antigens putatively implicated in acquisition of
      natural immunity to Neisseria meningitidis.
AB  - Sera from healthy human volunteers, patients convalescent from meningococcal
      meningitis, and mice immunized with outer membrane proteins from Neisseria
      meningitidis and Neisseria lactamica strains were used to analyze and identify
      antigens cross-reactive to both neisserial species. All classes of meningococcal
      proteins except class 1 (PorA) and class 5 cross-reacted with N. lactamica
      proteins and two other proteins of 65 and 55 kDa (an iron-regulated protein).
      Results obtained with the mouse sera demonstrate that cross-reactive antibodies
      can be elicited by either N. meningitidis or N. lactamica. These results support
      the suggestion that N. lactamica contributes to the development of natural
      immunity against N. meningitidis during the first years of life. The use of
      vaccines containing proteins other than PorA could interfere in colonization of
      mucosal surfaces by N. lactamica, hampering the natural mechanisms of immunity
      acquisition in humans. Only convalescent sera reacted with the 55 and 65 kDa
      proteins, which suggests that they might be relevant for pathogenicity.

PMID- 12208602
TI  - CD4(+) T cell levels are decreased during active CMV infection in kidney
      transplant recipients.
AB  - The numbers of T lymphocytes and T cell subsets (CD2(+), CD3(+), CD4(+), CD8(+)),
      activated T cells (CD26(+)), B cells (CD19(+)), granulocytes (CD15(+)) and
      natural killer cells (CD16/56) were monitored by flow cytometry in 79 kidney
      transplant recipients, 35 of whom had cytomegalovirus infection. The percentages
      of these cells were correlated with viral load, as determined by cytomegalovirus
      antigenemia. Development of cytomegaloviral infection coincided with a
      significant reduction in the percentages of CD4(+) (P < 0.005) and CD3(+) (P <
      0.05) cells. Monitoring of lymphocyte subsets may provide useful information on
      immunological events during cytomegaloviral infection.

PMID- 12208603
TI  - Epitope analysis of the FanC subunit protein of the K99 (F5) fimbriae of
      enterotoxigenic Escherichia coli using a recombinant fusion technique.
AB  - We have used a recombinant approach to characterise the B- and T-cell epitopes of
      FanC, the major subunit polypeptide of K99 (F5) fimbriae of enterotoxigenic
      Escherichia coli strains. This involved the fusion of FanC and its carboxy
      terminal truncated derivatives to a reporter, the E. coli alkaline phosphatase
      (PhoA), generating stable, recombinant fusions. The B-cell epitopes of FanC were
      characterised by Western blotting of FanC::PhoA fusion proteins with a polyclonal
      mouse antiserum directed against K99 fimbrial antigen, and with a panel of
      monoclonal antibodies generated to the K99 antigen. An attempt to characterise
      the T-cell epitopes of the fimbrial subunit was made by standard in vitro T-cell
      proliferation assay. Our results suggest that the B-cell epitopes of FanC are
      likely to be continuous, with a potentially immunodominant epitope at the carboxy
      terminus. However, T-cell proliferation assays with the FanC::PhoA fusion
      proteins did not indicate any immunodominant T-cell epitope(s). We hypothesise
      that fusion of FanC peptides to PhoA had resulted in altered folding of the
      peptides for antibody and T-cell recognition, highlighting the potential problems
      and drawbacks of the recombinant fusion technique in defining the epitopes of
      certain proteins.

PMID- 12208604
TI  - Immunogenicity and protective efficacy of three DNA vaccines encoding pre
      erythrocytic- and erythrocytic-stage antigens of Plasmodium cynomolgi in rhesus
      monkeys.
AB  - Although several malaria vaccine candidate antigens have been identified, the
      most suitable methods for their delivery are still being investigated. In this
      regard, direct immunization with DNA encoding these vaccine target antigens is an
      attractive alternative. Here, we have investigated the immune responses to DNA
      immunization with three major vaccine target antigens: the apical membrane
      antigen-1 and the 19-kDa C-terminal fragment of merozoite surface protein-1 from
      the erythrocytic stage, and the thrombospondin-related adhesive protein from the
      pre-erythrocytic stage of Plasmodium cynomolgi in rhesus monkeys. Antigen
      specific antibodies were developed in all the immunized monkeys and peripheral
      blood mononuclear cells from all immunized monkeys proliferated to different
      extents upon in vitro stimulation with the corresponding recombinant proteins.
      The immunized monkeys were challenged with P. cynomolgi sporozoites. All of the
      immunized animals developed infection but although there was no significant
      difference between the control and vaccinated animals in terms of pre-patent
      period, total duration of patency and primary peak parasitemia, the vaccinated
      animals had significantly lower secondary peak parasitemia than the control
      animals.

PMID- 12208605
TI  - T cell knockout mice have diminished alveolar bone loss after oral infection with
      Porphyromonas gingivalis.
AB  - Periodontal diseases are chronic inflammatory diseases that can result in
      resorption of the alveolar bone of the jaw. We have developed a murine model in
      which alveolar bone loss is induced by oral infection with Porphyromonas
      gingivalis, an oral anaerobic bacterium associated with periodontal disease in
      humans. Here we compared a strain of immunocompetent mice (C57BL/6J) to the same
      strain of mice made T cell deficient by genetic deletion of the alpha chain of
      their T cell receptors (C57BL/6J-Tcra). T cell deficiency did not affect the
      ability of P. gingivalis to implant in the oral cavity. The two strains of mice
      had equal percentages of P. gingivalis among their cultivable anaerobes 7 weeks
      after infection. The same bacterial load led to much less bone resorption in the
      T cell deficient mice than in the immune normal mice, measured as either the
      number of sites with significant loss, or as the total amount of bone resorbed. T
      cell deficient mice lost bone at only three out of 14 measurement sites, compared
      with eight out of 14 sites in the wild-type mice. The total amount of bone lost
      was 70% less in the T cell deficient mice. T cell deficient mice had lower titers
      of P. gingivalis-specific IgG than the wild-type mice after oral infection did,
      but the same titers of specific IgA. Lower titers did not correlate with greater
      bone loss. Antigen-activated T lymphocytes are known to induce
      osteoclastogenesis; here we demonstrate that T cell deletion decreases the amount
      of alveolar bone loss induced by infection of the murine oral cavity.

PMID- 12208606
TI  - Brefeldin A, a cytotoxin produced by Paecilomyces sp. and Aspergillus clavatus
      isolated from Taxus mairei and Torreya grandis.
AB  - Paecilomyces sp. and Aspergillus clavatus, which were isolated from Taxus mairei
      and Torreya grandis from southeast China, produced toxic metabolites when grown
      in liquid culture. Nuclear magnetic resonance techniques, infrared spectrometry,
      electrospray ionization mass spectroscopy and X-ray analysis identified brefeldin
      A, a bioactive metabolite produced by a number of fungal species belonging to the
      genera Alternaria, Ascochyta, Penicillium, Curvularia, Cercospora and
      Phyllosticta. This is the first report of the isolation of the cytotoxin from
      Paecilomyces sp. and A. clavatus. The relevance of brefeldin A to the association
      between these fungi and their host plants is discussed.

PMID- 12208607
TI  - Immune protection mediated by the probiotic Lactobacillus rhamnosus HN001 (DR20)
      against Escherichia coli O157:H7 infection in mice.
AB  - This study investigated the protective effects of feeding the immunoenhancing
      probiotic Lactobacillus rhamnosus HN001 against Escherichia coli O157:H7
      infection in murine (BALB/c and C57BL/6 mice) challenge infection models. Mice
      were fed milk-based diets supplemented with L. rhamnosus HN001 (3 x 10(8) cfu g(
      1)) for 7 days prior to and following oral challenge with E. coli O157:H7.
      Morbidity and feed intake were measured for 1 week following challenge; pathogen
      translocation to spleen, liver and blood, and humoral and cellular immunological
      responses (specific antibody and phagocytosis) were measured in a sub-sample of
      ostensibly healthy animals 1 week post-challenge. Results showed that, after
      challenge, L. rhamnosus HN001-fed mice exhibited lower cumulative morbidity and
      bacterial translocation rates, compared to non-probiotic-fed control mice.
      Significantly higher intestinal anti-E. coli IgA responses and blood leucocyte
      phagocytic activity were recorded among probiotic-fed mice compared to controls.
      These results demonstrate that feeding the probiotic L. rhamnosus HN001 to mice
      can reduce the severity of E. coli O157:H7 infection, and suggest that this
      reduction may be associated with enhanced humoral and cellular immune responses.

PMID- 12208608
TI  - HIV-1 genetic diversity in Western Brittany, France.
AB  - We describe human immunodeficiency virus type 1 (HIV-1) diversity in Western
      Brittany, France, and trace the dissemination of HIV-1 non-B subtype infection.
      The strategy for HIV-1 subtyping used involved subtype specific enzyme
      immunoassays, heteroduplex mobility assays and phylogenetic analysis of the
      sequences of env encoding the V3 loop region. Samples were obtained from 567
      patients: 465 (82%) were of subtype B and 66 (11.6%) were not (20 were subtype A,
      11 subtype C, four subtype D, seven subtype F, five subtype G and 19 others with
      circulating recombinant forms: 4CRF01_AE, 11CRF02_AG, 1H, 3CRF11_cpx). These
      findings are consistent with other studies of French populations. There is an
      epidemiological correlation between subtype B and homosexual or heterosexual
      contamination in France and between non-B subtype and heterosexual contamination
      in Africa.

PMID- 12208609
TI  - Mitogen-activated protein kinases regulate Mycobacterium avium-induced tumor
      necrosis factor-alpha release from macrophages.
AB  - Tumor necrosis factor-alpha (TNF-alpha) is one of the key cytokines elicited by
      host macrophages upon challenge with pathogenic mycobacteria. Infection of human
      peripheral blood mononuclear cells or the murine macrophage cell line J774A-1
      with Mycobacterium avium induced activation of the mitogen-activated protein
      kinases (MAPKs) ERK1/2, p38 and c-Jun N-terminal kinase. U0126, an MEK-specific
      inhibitor, abrogated M. avium-induced TNF-alpha secretion. Transfection of cells
      with dominant-negative MEK1 led to the suppression of TNF-alpha release in M.
      avium-challenged macrophages. M. avium activated p38 MAPK and use of the p38 MAPK
      inhibitor, SB203580, revealed that the p38 signaling pathway negatively regulates
      activation of ERK1/2 and release of TNF-alpha. Taken together, these results
      provide evidence that M. avium-induced TNF-alpha release from macrophages depends
      on an interplay between the ERK1/2 and the p38 MAPK signaling pathways.

PMID- 12208610
TI  - Antigenicity of Mycobacterium paratuberculosis superoxide dismutase in mice.
AB  - Mycobacterium paratuberculosis (MPT) is the etiologic agent of paratuberculosis.
      The disease is prevalent in cattle worldwide, and exacts a heavy financial toll.
      Effective control requires the development of acellular vaccines offering a
      better protection than the current available vaccines without side effects and
      allowing the discrimination between infected and vaccinated animals. We studied
      the immune response of mice to the MPT superoxide dismutase (SOD) alone or
      adjuvanted by Ribi. We cloned, overexpressed and purified this antigen in
      Escherichia coli. Spleen cells from immunized mice, after exposure to recombinant
      MPT SOD (MPT rSOD), produced significant levels of IFNgamma, TNFalpha and IL-6.
      IFNgamma and TNFalpha production was increased by the addition of Ribi. In
      contrast, low levels of NO, IL-4 and IL-10 were secreted by spleen cells culture
      from immunized mice. The immunoglobulin isotype distribution analysis showed that
      Ribi adjuvant clearly induced a significantly higher anti-MPT rSOD antibody
      production of all classes tested and decreased the IgG1/IgG2a ratio thus
      improving the Th1 response. Delayed-type hypersensitivity responses in mice
      footpads were observed only in mice immunized with MPT rSOD emulsified in Ribi.
      Vaccination of MPT rSOD emulsified with Ribi induced both a Th2 and Th1 type of
      immune response with the later slightly more pronounced. The results presented
      here on the immunogenicity of MPT SOD suggest that this antigen should be further
      tested as a candidate antigen for a future acellular vaccine against
      paratuberculosis.

PMID- 12208611
TI  - Cells behaving badly: a theoretical model for the Fas/FasL system in tumour
      immunology.
AB  - One proposed mechanism of tumour escape from immune surveillance is tumour up
      regulation of the cell surface ligand FasL, which can lead to apoptosis of Fas
      receptor (Fas) positive lymphocytes. Based upon this 'counterattack', we have
      developed a mathematical model involving tumour cell-lymphocyte interaction, cell
      surface expression of Fas/FasL, and their secreted soluble forms. The model
      predicts that (a) the production of soluble forms of Fas and FasL will lead to
      the down-regulation of the immune response; (b) matrix metalloproteinase (MMP)
      inactivation should lead to increased membrane FasL and result in a higher rate
      of Fas-mediated apoptosis for lymphocytes than for tumour cells. Recent studies
      on cancer patients lend support for these predictions. The clinical implications
      are two-fold. Firstly, the use of broad spectrum MMP inhibitors as anti
      angiogenic agents may be compromised by their adverse effect on tumour FasL up
      regulation. Also, Fas/FasL interactions may have an impact on the outcome of
      numerous ongoing immunotherapeutic trials since the final common pathway of all
      these approaches is the transduction of death signals within the tumour cell.

PMID- 12208612
TI  - Equivalence relationships between stage-structured population models.
AB  - Matrix population models are widely applied in conservation ecology to help
      predict future population trends and guide conservation effort. Researchers must
      decide upon an appropriate level of model complexity, yet there is little
      theoretical work to guide such decisions. In this paper we present an analysis of
      a stage-structured model, and prove that the model's structure can be simplified
      and parameterised in such a way that the long-term growth rate, the stable-stage
      distribution and the generation time are all invariant to the simplification. We
      further show that for certain structures of model the simplified models require
      less effort in data collection. We also discuss features of the models which are
      not invariant to the simplification and the implications of our results for the
      selection of an appropriate model. We illustrate the ideas using a population
      model for short-tailed shearwaters (Puffinus tenuirostris). In this example,
      model simplification can increase parameter elasticity, indicating that an
      intermediate level of complexity is likely to be preferred.

PMID- 12208613
TI  - Incorporating phenotype-dependent growth rates into the color-shift model for
      preneoplastic hepatocellular lesions.
AB  - Multi-stage models occupy a central position in modeling the carcinogenesis
      process. These models formalize the hypothesis that cells have to undergo several
      transformations on their way to malignancy. This hypothesis assumes that a
      preneoplastic cell of a later stage arises through a mutational event of a single
      cell of a previous stage and that preneoplastic cells proliferate clonally.
      However, there is some evidence that multi-stage models cannot adequately
      describe the formation and the progression of preneoplastic lesions at least in
      certain organs [Math. Biosci. 168 (2000) 167]. An alternative model assuming that
      all cells in a colony of altered hepatocytes change their phenotype more or less
      simultaneously rather than by mutation of single cells has already been
      introduced [Math. Biosci. 148 (1998) 181] and is called color-shift model (CSM).
      This model assumed deterministic phenotype-independent growth for the foci once
      they are generated. An expansion of the CSM allowing for variability between
      deterministic growth behaviour of phenotypically different colonies is presented
      (modCSM) and the model is applied to focal lesion data from a rat
      hepatocarcinogenesis experiment. The fit of the originally proposed and the
      modCSM are compared with respect to their ability to predict numbers and radii of
      preneoplastic cell foci.

PMID- 12208614
TI  - The effective number of a population that varies cyclically in size. II.
      Overlapping generations.
AB  - We consider haploid and dioecious age-structured populations that vary over time
      in cycles of length k. Results are obtained for both autosomal and sex-linked
      loci if the population is dioecious. It is assumed that k is small in comparison
      with numbers of haploid individuals (or of numbers of males and females) in any
      generation of a cycle. The inbreeding effective population size N(e) is then
      approximately given by the expression [T summation operator (k
      1)(j=0)1/[N(e)(j)T(j)]](-1), where N(e)(j) and T(j) are, respectively, the
      effective population size and generation interval that would hold if the
      population was at all times generated in the same way as at time j. The constant
      T, which is the effective overall generation interval, is defined to be k times
      the harmonic mean of the quantities T(j). Our expressions for T and N(e), in
      terms of N(e)(j) and T(j), are general, but the N(e)(j)s are derived under the
      assumption that offspring are produced according to Poisson distributions.

PMID- 12208615
TI  - Plasmid-bearing, plasmid-free organisms competing for two complementary nutrients
      in a chemostat.
AB  - A model of competition for two complementary nutrients between plasmid-bearing
      and plasmid-free organisms in a chemostat is proposed. A rigorous mathematical
      analysis of the global asymptotic behavior of the model is presented. The work
      extends the model of competition for a single-limited nutrient studied by
      Stephanopoulos and Lapidus [Chem. Engng. Sci. 443 (1988) 49] and Hsu, Waltman and
      Wolkowicz [J. Math. Biol. 32 (1994) 731].

PMID- 12208616
TI  - Mathematical analysis of the global dynamics of a model for HTLV-I infection and
      ATL progression.
AB  - Mathematical analysis is carried out that completely determines the global
      dynamics of a mathematical model for the transmission of human T-cell
      lymphotropic virus I (HTLV-I) infection and the development of adult T-cell
      leukemia (ATL). HTLV-I infection of healthy CD4(+) T cells takes place through
      cell-to-cell contact with infected T cells. The infected T cells can remain
      latent and harbor virus for several years before virus production occurs.
      Actively infected T cells can infect other T cells and can convert to ATL cells,
      whose growth is assumed to follow a classical logistic growth function. Our
      analysis establishes that the global dynamics of T cells are completely
      determined by a basic reproduction number R(0). If R(0)< or =1, infected T cells
      always die out. If R(0)>1, HTLV-I infection becomes chronic, and a unique endemic
      equilibrium is globally stable in the interior of the feasible region. We also
      show that the equilibrium level of ATL-cell proliferation is higher when the HTLV
      I infection of T cells is chronic than when it is acute.

PMID- 12208617
TI  - Dedication: gearing up for war.

PMID- 12208618
TI  - Commentary: gearing up for war.

PMID- 12208619
TI  - Nuclear terrorism: health and environmental hazards and threats from ionizing and
      nuclear radiation.

PMID- 12208620
TI  - The story of anthrax from antiquity to the present: a biological weapon of nature
      and humans.

PMID- 12208621
TI  - Bioterrorism and how to cope with it.

PMID- 12208622
TI  - Biological warfare and the skin I: bacteria and toxins.

PMID- 12208623
TI  - Biological warfare and the skin II: viruses.

PMID- 12208624
TI  - A spotlight on anthrax.

PMID- 12208625
TI  - A spotlight on smallpox.

PMID- 12208626
TI  - War burns: the blow and the cure.

PMID- 12208627
TI  - Cutaneous diseases from protective measures in soldiers and civilians.

PMID- 12208628
TI  - Gulf War syndrome.

PMID- 12208629
TI  - Coping with panic and fear of a nonconventional threat.

PMID- 12208630
TI  - Environmental skin diseases in military personnel.

PMID- 12208631
TI  - Unusual skin infections in military personnel.

PMID- 12208632
TI  - Skin diseases in war.

PMID- 12208633
TI  - Contact dermatitis in military personnel.

PMID- 12208635
TI  - Ground zero dermatology.

PMID- 12208634
TI  - Marching in the army: common cutaneous disorders of the feet.

PMID- 12208636
TI  - The other medicine: complementary and alternative--why, why not?

PMID- 12208637
TI  - Brain activation during script-driven imagery induced dissociative responses in
      PTSD: a functional magnetic resonance imaging investigation.
AB  - BACKGROUND: The goal of this study was to examine the neuronal circuitry
      underlying dissociative responses to traumatic script-driven imagery in sexual
      abuse-related posttraumatic stress disorder (PTSD). Pilot studies in our
      laboratory have shown that PTSD patients had very different responses to
      traumatic script-driven imagery. Approximately 70% of patients relived their
      traumatic experience and showed an increase in heart rate while recalling the
      traumatic memory. The other 30% of patients had a dissociative response with no
      concomitant increase in heart rate. This article focuses on the latter group.
      METHODS: The neuronal circuitry underlying dissociative responses in PTSD was
      studied using the traumatic script-driven symptom provocation paradigm adapted to
      functional magnetic resonance imaging (fMRI) at a 4 Tesla field strength in 7
      subjects with sexual-abuse-related PTSD and 10 control subjects. RESULTS:
      Compared with control subjects, PTSD patients in a dissociative state showed more
      activation in the superior and middle temporal gyri (BA 38), the inferior frontal
      gyrus (BA 47), the occipital lobe (BA 19), the parietal lobe (BA 7), the medial
      frontal gyrus (BA 10), the medial cortex (BA 9), and the anterior cingulate gyrus
      (BA 24 and 32). CONCLUSIONS: These findings suggest that prefrontal and limbic
      structures underlie dissociative responses in PTSD. Differences observed
      clinically, psychophysiologically, and neurobiologically between patients who
      respond to traumatic script-driven imagery with dissociative versus
      nondissociative responses may suggest different neuronal mechanisms underlying
      these two distinct reactions.

PMID- 12208638
TI  - 1 hz rTMS over the right prefrontal cortex reduces vigilant attention to unmasked
      but not to masked fearful faces.
AB  - BACKGROUND: Recent repetitive transcranial magnetic stimulation (rTMS) research
      in healthy subjects suggests that the emotions anger and anxiety are lateralized
      in the prefrontal cortex. Low-frequency rTMS over the right prefrontal cortex
      (PFC) shifts the anterior asymmetry in brain activation to the left hemisphere
      and reduces anxiety. The same rTMS technique results in enhanced anger-related
      emotional processing, observed as elevations in attention for angry faces. The
      current study used low-frequency rTMS over the right PFC and indexed selective
      attention to fearful faces, hypothesizing a reduction in attention for fearful
      faces, i.e., a reversal of the latter effect. METHODS: In a placebo-controlled
      design, 1 Hz rTMS at 130% of the individual motor threshold (MT) was applied
      continuously over the right PFC of eight healthy subjects for 20 minutes. Effects
      on motivated attention were investigated by means of an emotional Stroop task,
      indexing selective attention to masked and unmasked fearful faces. RESULTS:
      Vigilant attention for masked and unmasked fearful faces was observed after
      placebo stimulation. As hypothesized, rTMS reduced the vigilant emotional
      response to the fearful face, but only in the unmasked task. CONCLUSIONS: These
      data provide further support for the lateralization of the emotions anger and
      anxiety in the prefrontal cortex. In addition, the absence of an effect for
      masked fearful faces suggests that changes in emotional processing after a single
      session of rTMS predominantly involve the cortical affective pathways.

PMID- 12208639
TI  - Sex differences in stress responses: social rejection versus achievement stress.
AB  - BACKGROUND: Sex differences in stress responses may be one mechanism underlying
      gender differences in depression. We hypothesized that men and women would show
      different adrenocortical responses to different stressors. In particular, we
      predicted that women would show greater responses to social rejection stressors,
      whereas men would demonstrate greater responses to achievement stressors.
      METHODS: Following a rest session in which they habituated to the laboratory, 50
      healthy volunteers (24 men and 26 women, mean age 19.1, SD = 1.13) were randomly
      assigned to achievement or rejection stress conditions. The achievement condition
      involved a mathematical and a verbal challenge; the rejection condition involved
      two social interaction challenges. Self-reported affect and salivary cortisol
      were measured throughout each stress session (baseline, stress, and poststress
      periods). RESULTS: There were no sex differences in mood ratings following the
      stressors; however, cortisol responses showed the predicted gender by condition
      by time interaction. Men showed significantly greater cortisol responses to the
      achievement challenges, but women showed greater cortisol responses to the social
      rejection challenges. CONCLUSIONS: Women appear more physiologically reactive to
      social rejection challenges, but men react more to achievement challenges.
      Women's greater reactivity to rejection stress may contribute to the increased
      rates of affective disorders in women.

PMID- 12208640
TI  - Psychophysiological and subjective indicators of aversive pavlovian conditioning
      in generalized social phobia.
AB  - Aversive conditioning has been proposed as an important etiologic mechanism in
      social phobia; however, empirical evidence is scarce and has not relied on a
      detailed analysis of the acquisition and extinction of the conditioned emotional
      response. Fourteen men sustaining generalized social phobia and 19 healthy
      control subjects participated in differential aversive conditioning with two
      neutral faces as conditioned stimuli and an aversive odor as unconditioned
      stimulus. Subjective and peripheral physiological responses were obtained. Both
      groups were successfully conditioned as reflected by differential subjective
      (valence, arousal, subjective unconditioned stimulus expectancy) and peripheral
      physiological responses (skin conductance, startle response). There was no
      evidence for an enhanced conditionability in the social phobics; however, they
      showed an enhanced unconditioned stimulus expectancy, especially for the
      nonreinforced conditioned stimuli during acquisition, and a delayed extinction of
      the conditioned skin conductance response as well as a certain dissociation
      between subjective and physiological responses.The enhanced unconditioned
      stimulus expectancy during acquisition and the overall elevated subjective
      arousal suggest that, under threat, subjects with generalized social phobia may
      be more prone to associate neutral social cues and an aversive outcome.
      Furthermore, delayed extinction of the conditioned response seems to contribute
      to the etiology and maintenance of generalized social phobia.

PMID- 12208641
TI  - Schizophrenia and affective disorder show different visual scanning behavior for
      faces: a trait versus state-based distinction?
AB  - BACKGROUND: Abnormal visual scanpaths to faces and facial expressions in
      schizophrenia may underlie schizophrenic subjects' disturbed interpersonal
      communication. This study is the first to examine the specificity of these
      impairments to schizophrenia, by including an affective disorder psychiatric
      control group. METHODS: The visual scanpath performance of 65 schizophrenia, 52
      affective disordered, and 61 control subjects were compared in two experiments.
      In the "face recognition" experiment, subjects viewed four identifiable (non
      degraded) neutral faces versus four matched non-identifiable (degraded) control
      faces. In the "facial affect recognition" experiment, subjects viewed positive
      (happy), negative (sad), and neutral (control) facial emotion stimuli. Concurrent
      behavioral tasks were face matching (face recognition) and expression matching
      (facial affect recognition), each under two multiple-choice conditions (7 or 3
      options). RESULTS: Scanpath disturbances were most apparent in schizophrenia
      subjects, who maintained a comparatively "restricted" scanpath style to all face
      stimuli. Schizophrenics subjects also showed the greatest recognition
      difficulties, particularly for neutral and happy faces. Scanpath parameters for
      affective disorder subjects differed only from the schizophrenia (but not the
      control) group, except for attention to facial features where they generally
      avoided facial features in all expressions and showed the greatest attentional
      problems of all groups for degraded faces. CONCLUSIONS: Our results suggest that
      a global restriction of visual scanpaths is specific to schizophrenic psychosis
      and might be a trait marker for this disorder, whereas scanpath abnormalities in
      affective disorder might instead reflect severe state-based (or discrete)
      attentional disturbances.

PMID- 12208642
TI  - Association between skin test diagnosed atopy and professionally diagnosed
      depression: a Northern Finland 1966 Birth Cohort study.
AB  - BACKGROUND: Several studies have suggested an association between IgE-mediated
      atopic allergies and depression, although thus far no epidemiologic evidence
      involving a large, unselected, general-population sample and valid methods in
      diagnosing atopy support this putative association. METHODS: We used the Northern
      Finland 1966 Birth Cohort, which was followed prospectively to age 31. Of the
      total cohort, 5428 individuals underwent skin tests for three of the most common
      allergens (i.e., cat, birch, and timothy grass) and for dust mites
      (Dermatophagoides pteronyssinus). Data on doctor-diagnosed lifetime depression
      were obtained from questionnaires. RESULTS: After adjusting for social class,
      mothers' parity, place of residence, and psychiatric morbidity, the logistic
      regression analysis showed that the risk of developing depression when compared
      with nonatopic subjects increased up to 1.8-fold in atopic women (adjusted odds
      ratio 1.8, 95% confidence interval [CI] 1.2-2.6) and, when compared with skin
      test-negative female subjects without allergic symptoms, reached 2.7-fold
      increases (95% CI 1.6-4.6) in those suffering from clinically manifest atopic
      disorders. Corresponding associations were not found among male subjects.
      CONCLUSIONS: Our results indicate that women suffering from atopic diseases may
      possess an elevated risk for developing depression during early adulthood.
      Possible background theories (i.e., genetic abnormalities in serotonin
      metabolism, hypothalamic-pituitary-adrenal axis dysfunction, and histamine
      theory) are discussed.

PMID- 12208643
TI  - Obsessive compulsive disorder among idiopathic focal dystonia patients: an
      epidemiological and family study.
AB  - BACKGROUND: A disturbed function of striato-thalamo-cortical circuitry is
      hypothesized to underlie idiopathic focal dystonia (IFD) and obsessive compulsive
      disorder (OCD), two severe and disabling neurologic and psychiatric disorders.
      Previous studies on small samples showed either higher obsessionality scores or
      higher frequency of OCD in dystonic patients than in normal control subjects. The
      aim of this study was to evaluate the frequency and familial loading of OCD in a
      population of patients with IFD. METHODS: We evaluated OCD diagnosis and family
      history in 76 patients affected by IFD. RESULTS: Of our subjects 19.7% satisfied
      DSM-IV criteria for OCD diagnosis and had a family morbidity risk for OCD of
      13.8%, significantly higher than that found in the general population.
      CONCLUSIONS: Our results support the hypothesis of a common pathologic background
      for OCD and IFD, at least in a subgroup of IFD, indicating basal ganglia
      dysfunction.

PMID- 12208644
TI  - Astrocytic basic fibroblast growth factor expression in dopaminergic regions
      after perinatal anoxia.
AB  - BACKGROUND: Perinatal anoxia leads to persistent behavioral and neurochemical
      alterations suggestive of sensitized dopaminergic function. Because astrocytic
      basic fibroblast growth factor (bFGF) activity in the midbrain dopaminergic cell
      body region is required for the development of enduring changes in dopaminergic
      function induced by stimulant drugs, we investigated the effects of intrauterine
      anoxia on astrocytic bFGF expression in dopaminergic regions at 2 weeks of age
      and after a stress manipulation in adults. METHODS: We examined bFGF
      immunoreactivity in dopaminergic regions of young and adult rats born by cesarean
      section, cesarean section + 15 min of intrauterine anoxia, or vaginally. bFGF
      immunoreactivity was also assessed before and after tail-pinch stress in adult
      animals exposed to the same perinatal interventions. RESULTS: Perinatal anoxia
      produced persistent decreases in basal bFGF immunoreactivity in the ventral
      tegmental area (VTA), but enhanced the effect of stress on VTA bFGF
      immunoreactivity. CONCLUSIONS: Perinatal anoxia has enduring effects on VTA bFGF
      immunoreactivity and influences adult neuroadaptations to stress. The mechanisms
      whereby perinatal anoxia alters dopaminergic function may be similar to those
      responsible for the development of sensitization to stimulant drugs and may
      involve bFGF.

PMID- 12208645
TI  - High-dose ascorbic acid increases intercourse frequency and improves mood: a
      randomized controlled clinical trial.
AB  - BACKGROUND: Ascorbic acid (AA) modulates catecholaminergic activity, decreases
      stress reactivity, approach anxiety and prolactin release, improves vascular
      function, and increases oxytocin release. These processes are relevant to sexual
      behavior and mood. METHODS: In this randomized double-blind, placebo-controlled
      14 day trial of sustained-release AA (42 healthy young adults; 3000 mg/day
      Cetebe) and placebo (39 healthy young adults), subjects with partners recorded
      penile-vaginal intercourse (FSI), noncoital partner sex, and masturbation in
      daily diaries, and also completed the Beck Depression Inventory before and after
      the trial. RESULTS: The AA group reported greater FSI (but, as hypothesized, not
      other sexual behavior) frequency, an effect most prominent in subjects not
      cohabiting with their sexual partner, and in women. The AA but not placebo group
      also experienced a decrease in Beck Depression scores. CONCLUSIONS: AA appears to
      increase FSI, and the differential benefit to noncohabitants suggests that a
      central activation or disinhibition, rather than peripheral mechanism may be
      responsible.

PMID- 12208646
TI  - Low CSF 5-HIAA level in high-lethality suicide attempters: fact or artifact?

PMID- 12208649
TI  - Infant perceptual and conceptual categorization: the roles of static and dynamic
      stimulus attributes.
AB  - Infants' categorization of animals and vehicles based on static vs. dynamic
      attributes of stimuli was investigated in five experiments (N=158) using a
      categorization habituation-of-looking paradigm. In Experiment 1, 6-month-olds
      categorized static color images of animals and vehicles, and in Experiment 2, 6
      month-olds categorized dynamic point-light displays showing only motions of the
      same animals and vehicles. In Experiments 3, 4, and 5, 6- and 9-month-olds were
      tested in an habituation-transfer paradigm: half of the infants at each age were
      habituated to static images and tested with dynamic point-light displays, and the
      other half were habituated to dynamic point-light displays and tested with static
      images. Six-month-olds did not transfer. Only 9-month-olds who were habituated to
      dynamic displays showed evidence of category transfer to static images. Together
      the findings show that 6-month-olds categorize animals and vehicles based on
      static and dynamic information, and 9-month-olds can transfer dynamic category
      information to static images. Transfer, static vs. dynamic information, and age
      effects in infant categorization are discussed.

PMID- 12208650
TI  - Radical concept nativism.
AB  - Radical concept nativism is the thesis that virtually all lexical concepts are
      innate. Notoriously endorsed by Jerry Fodor, radical concept nativism has had few
      supporters. However, it has proven difficult to say exactly what's wrong with
      Fodor's argument. We show that previous responses are inadequate on a number of
      grounds. Chief among these is that they typically do not achieve sufficient
      distance from Fodor's dialectic, and, as a result, they do not illuminate the
      central question of how new primitive concepts are acquired. To achieve a fully
      satisfactory response to Fodor's argument, one has to juxtapose questions about
      conceptual content with questions about cognitive development. To this end, we
      formulate a general schema for thinking about how concepts are acquired and then
      present a detailed illustration.

PMID- 12208651
TI  - Visual mental images can be ambiguous: insights from individual differences in
      spatial transformation abilities.
AB  - The debate about whether objects in mental images can be ambiguous has produced
      ambiguous results. In some studies, participants could not reinterpret objects in
      images, but even in the studies where participants could reinterpret visualized
      patterns, the results are not conclusive. The present study used a novel task to
      investigate the reinterpretation of ambiguous figures in imagery, which required
      the participants to mentally rotate a figure 180 degrees before attempting to
      "see" an alternate interpretation. In addition, the participants did not know the
      purpose of the study in advance, nor did they see alternate interpretations of
      the stimuli; moreover, we explicitly measured individual differences in key
      mental imagery abilities. Eight of the 44 participants discovered the alternate
      version while they were memorizing the figure; 16 reported it after mentally
      rotating an image; and 20 were not able to "see" the alternate version. The
      ability to rotate images, assessed with an independent task, was highly
      associated with reports of image reversals, whereas measures of other imagery
      abilities were not.

PMID- 12208652
TI  - Calculation, culture, and the repeated operand effect.
AB  - A basic phenomenon of cognitive arithmetic is that problems composed of a
      repeated operand, so-called "ties" (e.g. 6+6, 7 x 7), typically are solved more
      quickly and accurately than comparable non-tie problems (e.g. 6+5, 7 x 8). In
      Experiment 1, we present evidence that the tie effect is due to more efficient
      memory for ties than for non-ties, which participants reported solving more often
      using calculation strategies. The memory/strategy hypothesis accounts for
      differences in the tie effect as a function of culture (Asian Chinese vs. non
      Asian Canadian university students), operation (addition, multiplication,
      subtraction, and division), and problem size (numerically small vs. large
      problems). Nonetheless, Blankenberger (Cognition 82 (2001) B15) eliminated the
      tie response time (RT) advantage by presenting problems in mixed formats (e.g. 4
      x four), which suggests that the tie effect with homogenous formats (4 x 4 or
      four x four) is due to encoding. In Experiment 2, using simple multiplication
      problems, we replicated elimination of the tie effect with mixed formats, but
      also demonstrated an interference effect for mixed-format ties that slowed RTs
      and increased errors relative to non-tie problems. Additionally, practicing non
      tie problems in both orders (e.g. 3 x 4 and 4 x 3) each time ties were tested
      once (cf. Cognition 82 (2001) B15) reduced the tie effect. The format-mismatch
      effect on ties, combined with a reduced tie advantage because of extra practice
      of non-ties, eliminated the tie effect. Rather than an encoding advantage, the
      results indicate that memory access for ties was better than for non-ties.

PMID- 12208653
TI  - Meaningful processing of meaningless stimuli: the influence of perceptual
      experience on early visual processing of faces.
AB  - The N170 is an event-related potential component associated with extrastriate
      visual mechanisms involved in detecting human faces and leading to their
      characteristic structural encoding. Consequently the N170 discriminates the
      processing of stimuli providing physiognomic information from the processing of
      other, similarly complex, visual patterns. We have used this effect to explore
      the top-down influence of newly acquired experience on the initial visual
      categorization of physiognomic stimuli. Schematic faces having the inner
      components mislocated did not elicit an N170 effect in naive participants.
      However, after normally configured versions of the schematic faces were exposed,
      suggesting what the ambiguous patterns represented, the same patterns elicited an
      N170 effect as conspicuous as that elicited by regular schematic faces. This
      priming effect, which changed the visual processing of distorted faces in
      extrastriate regions, could not be explained by post-perceptual decisions.
      Although accounts based on changes in focal attention, or within-vision
      constraints could not be categorically rejected, this outcome might suggest
      cognitive penetrability of early visual categorization.

PMID- 12208654
TI  - Rule learning by cotton-top tamarins.
AB  - Previous work suggests that human infants are capable of rapidly generalizing
      patterns that have been characterized as abstract algebraic rules (Science 283
      (1999) 77), a process that may play a pivotal role in language acquisition. Here
      we explore whether this capacity is uniquely human and evolved specifically for
      the computational problems associated with language, or whether this mechanism is
      shared with other species, and therefore evolved for problems other than
      language. We used the same materials and methods that were originally employed in
      tests of human infants to assess whether cotton-top tamarin monkeys can extract
      abstract algebraic rules. Specifically, we habituated subjects to sequences of
      consonant-vowel syllables that followed one of two patterns, AAB (e.g. wi wi di)
      or ABB (le we we). Following habituation, we presented subjects with two novel
      test items, one with the same pattern as that presented during habituation and
      one with a different pattern. Like human infants, tamarins were more likely to
      dishabituate to the test item with a different pattern. We conclude that the
      capacity to generalize rule-like patterns, at least at the level demonstrated,
      did not evolve specifically for language acquisition, though it remains possible
      that infants might use such rules during language acquisition.

PMID- 12208655
TI  - Metalloproteinases and the modulation of GH signaling.
AB  - The metzincin metalloproteinase, tumor necrosis factor-alpha-converting enzyme
      (TACE), also known as ADAM (a disintegrin and metalloproteinase) 17, has recently
      been identified as an important enzyme for cleavage of the GH receptor (GHR) and
      shedding of GH-binding protein (GHBP). Proteolysis can be induced by phorbol
      esters, platelet-derived growth factor and serum; it is dependent on protein
      kinase C and partially on MAP kinase pathways. Proteolysis occurs at the cell
      surface, leading to extracellular release of GHBP and intracellular GHR remnant
      accumulation. The GHR remnant is further processed by gamma-secretase activity,
      possibly leading to biologically active products. TACE-dependent GHR proteolysis
      can be inhibited by GH as the dimerized GHR is resistant to cleavage. The
      cleavage site lies within a short juxtamembranous stem region that extends
      between the transmembrane helix and the globular dimerization domain of the GHR.
      GHR proteolysis leads to downregulation of functional GHRs at the cell surface,
      and has complex secondary effects on GH action via GHBP and GHR remnant
      generation.

PMID- 12208656
TI  - Oestrogen-induced apoptosis in colonocytes expressing oestrogen receptor beta.
AB  - Epidemiological studies of postmenopausal hormone replacement therapy show a
      reduction in the risk of developing colon cancer, and animal studies using 17beta
      oestradiol (E(2)) demonstrate a decreased incidence of chemically-induced colon
      cancer. Using the colon cancer cell line, COLO205, we found that E(2) induced a
      dose-dependent increase in DNA fragmentation and nuclear condensation,
      significant effects being seen at 10(-12 )mol/l. BSA-conjugated E(2), which
      cannot enter cells, was ineffective at inducing apoptosis in COLO205 cells,
      indicating that E(2) was not acting through a cell-membrane receptor. E(2) did
      not induce the morphological changes characteristic of differentiation. Using RT
      PCR we found that the oestrogen receptor alpha (ERalpha) isoform was absent in
      the COLO205 cell line in contrast to CACO-2, LoVo and SW620 cells, but mRNAs for
      ERbeta1, -beta2, -beta5 and -beta6 isoforms were detected. Western immunoblotting
      results showed full-length ERbeta protein but no detectable ERalpha in COLO205
      cells. In normal human colon tissue samples immunoreactive ERbeta was found but
      ERalpha was barely detectable. Expression of ERbeta was lost in some colon cancer
      specimens and reduced in others. We conclude that E(2), through ERbeta, at
      concentrations found during replacement therapy, may inhibit the development of
      colon cancer by inducing apoptosis.

PMID- 12208658
TI  - GH and cortisol rebound rise during and following a somatostatin infusion:
      studies in dogs with the use of a GH-releasing peptide.
AB  - GH-releasing peptides (GHRPs), a class of small synthetic peptide and non-peptide
      compounds, act on specific receptors at both the pituitary and the hypothalamic
      level to stimulate GH release in both humans and other animals. GHRPs, like
      corticotropin-releasing hormone (CRH), also possess acute ACTH- and cortisol
      releasing activity, although the mechanisms underlying the stimulatory effect of
      GHRPs on the hypothalamo-pituitary-adrenal (HPA) axis are still unclear. In
      recent years, studies in humans and other animals have provided evidence that the
      rebound GH rise which follows withdrawal of an infusion of somatostatin (SS)
      (SSIW) is due, at least in part, to the functional activation of GH-releasing
      hormone (GHRH) neurons of the recipient organism. Unexpectedly, in humans, SS
      infusion, at a dose inhibiting basal GH secretion, has been associated with an
      activation of the HPA axis, leading to the hypothesis that this response was
      mediated, at least in part, by a central nervous system ACTH-releasing mechanism
      activated by the SS-induced decrease in GH secretion. Interestingly, the rebound
      GH rise which follows SSIW was magnified by the administration, before SS
      withdrawal, of a GHRP, implying that the SSIW approach could also be exploited to
      investigate in vivo the functional interaction in the process of GH and/or
      ACTH/cortisol secretion between endogenous GHRH (and/or other ACTH-releasing
      mechanisms) and GHRPs. In the present study, six young beagle dogs were given, on
      different occasions, at the beginning and at the end of a 3-h i.v. infusion of SS
      or saline (SAL), a bolus of physiological SAL or a GHRP compound, EP51216. SSIW
      induced a GH rebound rise without affecting plasma cortisol concentrations, while
      the withdrawal of SAL infusion was ineffective on either hormone paradigm.
      Administration of EP51216 at the beginning of SAL infusion evoked release of both
      GH and cortisol, whereas EP51216 administration at the withdrawal of SAL infusion
      evoked somatotroph and cortisol responses which were reduced in amplitude and
      duration. SS infusion significantly reduced the secretion of GH elicited by
      EP51216 but did not affect the rise of plasma cortisol levels. Interestingly,
      SSIW resulted in a marked enhancement of the somatotroph and cortisol responses
      evoked by EP51216. The marked rise of plasma GH levels induced by the GHRP after
      SSIW recalled that occurring after acute combined administration of recombinant
      human GHRH and EP51216, implying that exogenously delivered GHRP had synergized
      with the endogenous GHRH release triggered by SSIW. In contrast, acute combined
      administration of GHRH and the GHRP induced a cortisol response not different
      from that induced by GHRP alone, indicating that endogenous GHRH release was not
      involved in the enhanced cortisol response following EP51216 administration after
      SSIW. Similarly, the direct involvement of endogenous CRH could be ruled out,
      since i.v. administration of ovine CRH after SSIW evoked cortisol peak levels not
      different from those evoked by CRH at the withdrawal of SAL infusion. In
      conclusion, enhancement of the GH response to EP51216 alone by SSIW, to an extent
      reminiscent of that following combined administration of GHRH and EP61216,
      reinforces the view that SSIW elicits release of endogenous GHRH. Further studies
      are indeed necessary for a better understanding of the mechanisms underlying the
      enhanced cortisol response, since from now on the involvement of endogenous GHRH
      or CRH can be ruled out.

PMID- 12208657
TI  - Proteasome inhibitors induce apoptosis in growth hormone- and prolactin-secreting
      rat pituitary tumor cells.
AB  - Proteasome inhibitors induce apoptosis in some malignant cells, and we show here
      that these inhibitors induce apoptosis in rat pituitary MMQ and GH3 tumor cells
      but not in normal pituitary cells. Three proteasome inhibitors, PSI, MG-132, and
      lactacystin, but not the calpain inhibitor, ALLM, dose- and time-dependently
      caused apoptosis in these cells, and 10 microM PSI caused apoptosis in 70% of MMQ
      cells and in 25% of GH3 cells within 24 h. A lower PSI dose (10 nM) inhibited GH3
      cell growth without causing significant apoptosis or affecting prolactin
      secretion. Primary rat pituitary cells were resistant to both PSI and MG-132 and
      did not undergo apoptosis. In MMQ cells, DNA synthesis was slowed (approximately
      30%) after 6 h of 10 microM PSI treatment and a partial cell cycle block at G2/M
      was evident after 8 h. Colorimetric caspase substrate assay and Western blotting
      of caspase substrates showed that caspases 2 and 3 are activated by PSI while
      caspases 6 and 8 remained inactive. A broad-range caspase inhibitor, caspase
      inhibitor III, prevented apoptosis induced by PSI. The results show that
      proteasome inhibitors induce apoptosis in rat pituitary tumor cells by specific
      caspase activation. This novel group of drugs may potentially be used in
      treatment of aggressive pituitary tumors, especially as their action appears
      relative for tumor cells.

PMID- 12208659
TI  - Identification of a cDNA encoding a novel amphibian growth hormone-releasing
      peptide and localization of its transcript.
AB  - Recently, we identified in the bullfrog brain a novel neuropeptide with a C
      terminal Leu-Pro-Leu-Arg-Phe-NH(2) sequence. This amphibian neuropeptide was
      shown to stimulate growth hormone (GH) release in vitro and in vivo and so was
      designated frog GH-releasing peptide (fGRP). In this study, we cloned a cDNA
      encoding fGRP from the bullfrog brain by a combination of 3' and 5' rapid
      amplification of cDNA ends (RACE). The deduced fGRP precursor consisted of 221
      amino acid residues, encoding one fGRP and three putative fGRP-related peptides
      that included Leu-Pro-Xaa-Arg-Phe-NH(2) (Xaa=Leu or Gln) at their C-termini. All
      these peptide sequences were flanked by a glycine C-terminal amidation signal and
      a single basic amino acid on each end as an endoproteolytic site. Northern blot
      analysis detected a single band of approximately 1.0 kb, indicating that no
      alternatively spliced forms were present. Such an apparent migration was in
      agreement with the estimated length of the cDNA, 902 bp. In situ hybridization
      further revealed the cellular localization of fGRP mRNA in the suprachiasmatic
      nucleus in the hypothalamus. In addition to fGRP, its related peptides may be
      hypothalamic factors involved in pituitary hormone secretion.

PMID- 12208660
TI  - Defects in growth and bone metabolism in klotho mutant mice are resistant to GH
      treatment.
AB  - Klotho mutant (kl/kl) mice exhibit growth retardation after weaning, and previous
      electron microscopic examination of GH-producing cells in pituitary glands
      revealed a reduction in GH granules. However, it has not been known whether
      growth retardation in klotho mutant mice is related to the loss of GH function.
      We therefore examined whether treatment with GH could rescue the retardation of
      growth. At the end of 3 weeks of treatment with human GH, the body weight of wild
      type (WT) mice was increased. In contrast, body weight was not increased in
      klotho mutant mice even after the treatment with human GH. Another feature of
      klotho mutant mice is the presence of osteopetrosis in the epiphyses of long
      bones and vertebrae. Treatment with human GH increased trabecular bone volume in
      the epiphyseal region of WT tibiae. Interestingly, increase in trabecular bone
      volume by GH treatment was also observed in klotho mutant mice and, therefore,
      the phenotype of high bone volume in the klotho mice was further enhanced. These
      findings indicate that a GH receptor system in cancellous bones could operate in
      mutant mice. Thus, growth retardation in the klotho mutant mice is resistant
      against GH treatment even when these mice respond to GH treatment in terms of
      cancellous bone volume.

PMID- 12208661
TI  - Affected skeletal growth but normal bone mineralization in rat offspring after
      prenatal dexamethasone exposure.
AB  - Events occurring early in life or prenatally are able to play important roles in
      the pathogenesis of diseases in adult life. Different sorts of stress or hormonal
      influences, during particular periods of pregnancy, may result in persisting or
      transient changes in physiology. Glucocorticoids are used for the treatment of a
      variety of diseases, to promote organ maturation and to prevent preterm delivery.
      Glucocorticoids are also known to affect skeletal growth and adult bone
      metabolism. The aim of the present study was to investigate whether exposure to
      dexamethasone (Dex) during fetal life has any effect on skeletal growth and/or
      bone mineral density in adult rat offspring. Pregnant rats were given injections
      of either Dex (100 micro g/kg) or vehicle on days 9, 11 and 13 of gestation. Dex
      exposed male but not female rat offspring showed transient increases in crown
      rump length and tibia and femur lengths at 3-6 weeks of age. In contrast, the
      cortical bone dimensions were altered in 12-week-old female but not male Dex
      exposed offspring. The areal bone mineral densities of the long bones and the
      spine, as determined by dual X-ray absorptiometry, and trabecular as well as
      cortical volumetric bone mineral density, as measured using peripheral
      quantitative computerized tomography, were unchanged in both male and female Dex
      exposed offspring. In conclusion, prenatal Dex exposure affects skeletal growth
      in a gender-specific manner, while the mineralization of bones is unaffected in
      both male and female offspring.

PMID- 12208662
TI  - The effects of recombinant human parathyroid hormone, rhPTH(1-84), on bone mass
      in undernourished rats.
AB  - Energy intake restriction reduces bone formation both in protein-energy
      malnourished children and in undernourished rats, and such conditions might cause
      partial or irreversible bone loss. Because the use of anti-resorptive agents in
      this situation is seemingly limited, we examined the effect of the anabolic
      agent, recombinant human parathyroid hormone (rhPTH(1-84)), on bones in
      undernourished conditions. First, the osteopenic changes of rat bones with 40%
      restricted diet for 4 weeks were confirmed. Subsequently, another set of the rats
      were randomized into four groups and studied for 8 weeks: the freely fed group
      (control group); the restricted diet, then freely fed group (restriction-ad
      libitum group); the restricted diet-vehicle-treated group (restriction-vehicle
      group); and the restricted diet-PTH-treated group (restriction-PTH group). In the
      restriction-vehicle group, total femoral bone mineral density (BMD) was lower and
      femoral length was shorter than the control group by 15.4% and 8.1% respectively
      (P<0.05). In the restriction-ad libitum group, these parameters recovered fully
      to those of the control group. In the case of intermittent PTH treatment in the
      persistent undernourished state, the BMD of total femur caught up with those of
      the control or the restriction-ad libitum group. However, the femoral length
      remained shorter than those of the other groups. Serum osteocalcin was
      significantly reduced in continuously undernourished rats, whereas it was
      elevated in the restriction-PTH group. In conclusion, BMD of total femur was low
      in undernourished rats. However, it increased after re-feeding ad libitum or
      intermittent PTH treatment. We suggest that rhPTH(1-84) may be a possible
      therapeutic agent for ongoing bone loss, especially in patients in a chronically
      undernourished condition.

PMID- 12208663
TI  - The effect of maternal prolactin infusion during pregnancy on fetal adipose
      tissue development.
AB  - The present study determines whether maternal administration of prolactin (PRL)
      to dams promotes the abundance of the brown adipose tissue-specific uncoupling
      protein-1 (UCP1) in fetal and neonatal rat pups. Recombinant PRL (24 micro g/kg
      per day), or an equivalent volume of saline, were infused into dams (n=19 per
      group) throughout pregnancy from 12 h after mating. Interscapular brown adipose
      tissue was sampled either from fetuses at 19.5 days of gestation (term=21.5 days)
      or from neonatal rat pups at approximately 18 h after birth. The abundance of
      UCP1 was determined by immunoblotting on adipose tissue samples from individual
      pups and pooled from groups of pups. This analysis was complemented by
      immunocytochemistry on representative adipose tissue samples. Maternal PRL
      infusion resulted in a greater abundance of UCP1 in fetal rats at 19.5 days of
      gestation (control: 97.2+/-8.4% reference; PRL: 525.6+/-74.4% reference; P<0.001)
      and in neonates 18 h after birth. In contrast, the abundance of the outer
      mitochondrial membrane protein voltage-dependent anion channel was unaffected by
      PRL. Neonatal adipose tissue sampled from pups born to PRL-infused dams possessed
      fewer lipid droplets, but more UCP1, as determined by immunocytochemistry. Fetal,
      but not maternal, plasma leptin concentrations were also increased by maternal
      PRL administration. In conclusion, as rats are altricial, and the potential
      thermogenic activity of brown adipose tissue develops over the first few days of
      postnatal life, these changes prior to, and at the time of, birth implicate PRL
      in fetal and neonatal adipose tissue maturation.

PMID- 12208664
TI  - Detection of oestrogenic activity of steroids present during mammalian gestation
      using oestrogen receptor alpha- and oestrogen receptor beta-specific in vitro
      assays.
AB  - Numerous steroid hormones are present in the foetus but their potential to
      activate oestrogen receptor (ER) alpha and/or beta is largely unknown. In this
      study, in vitro assays were developed to rapidly and specifically detect ERalpha
      or ERbeta activation by these steroid hormones. Our results showed that several
      oestrogen precursors and androgens are able to activate both ERalpha and ERbeta.
      Of special interest is that some of these precursors are able to activate ERalpha
      and ERbeta at concentrations that are present during human gestation. Moreover,
      some precursors (dehydroepiandrosterone (DHEA) and 17-hydroxylated pregnenolone
      sulphate) and androgens (5-androsten-3beta,16alpha,17beta-triol and testosterone)
      showed a more than 100-fold relative preference for ERbeta transactivation over
      ERalpha transactivation when compared with 17beta-oestradiol. Due to their
      relatively high levels, the precursor steroids DHEA and pregnenolone may be of
      particular importance in the regulation of ERbeta activity in vivo. To obtain
      information about the oestrogenic activity of the total pool of steroid hormones
      present during mammalian gestation, steroids were extracted from mouse embryos at
      different prenatal stages and assayed for oestrogenic activity in the established
      in vitro assays. Oestrogenic activity was detected in steroid extracts from all
      stages tested. This study has demonstrated that oestrogen receptor agonists are
      present in the murine embryo and that oestrogen precursors may contribute to the
      total pool of agonists during foetal life.

PMID- 12208665
TI  - Dehydroepiandrosterone treatment attenuates oestrogen-induced pituitary
      hyperplasia.
AB  - The physiological importance of and therapeutic interest in
      dehydroepiandrosterone (DHEA) has been predominantly in relation to its action as
      an inhibitor of the promotion and progression of several kinds of tumours,
      including those of breast, prostate, lung, colon, liver and skin tissues. The aim
      of the present study was to determine the role of DHEA in diethylstilboestrol
      (DES)-induced pituitary hyperplasia. Female Sprague-Dawley rats were divided into
      four treatment groups: DES (implanted s.c. with a 20 mg DES pellet), DHEA (two 50
      mg DHEA pellets), DHEA/DES (both DHEA and DES pellets), and controls (not
      implanted). Every week, all rats were weighed and cycled, and jugular blood
      samples were obtained. After 7 weeks, rats were killed. Hypophyses were removed
      and weighed, and serum prolactin, GH, IGF-I and leptin levels were assayed by
      RIA. DHEA cotreatment reduced pituitary enlargement by 39% in DES-treated rats.
      It also reduced the hyperprolactinaemia (280.4+/-43.6 ng/ml for DHEA/DES vs
      823.5+/- 127.1 ng/ml for DES) and partially reversed the loss of body weight
      induced by DES. DHEA treatment did not modify the effects of DES on serum GH, IGF
      I and leptin levels. But DHEA per se also increased pituitary weight and induced
      hyperprolactinaemia, although to a lesser degree than DES. We conclude that DHEA
      administration has beneficial effects on oestrogen-induced pituitary hyperplasia
      and hyperprolactinaemia, but the fact that DHEA per se also induces diverse
      hormonal effects and a slight pituitary enlargement limits its use as a possible
      therapeutic drug.

PMID- 12208666
TI  - Peripheral but not central leptin prevents the immunosuppression associated with
      hypoleptinemia in rats.
AB  - Leptin is a peripheral immunoenhancing reagent that directly activates splenic
      lymphocytes in mice. We found that a 48 h fast in rats resulted in a decrease in
      serum leptin that was accompanied by a lower delayed-type hypersensitivity (DTH)
      response. Peripheral leptin replacement completely restored this response in
      fasted animals. We employed a recombinant adeno-associated virus (rAAV) system to
      deliver leptin gene directly into rat brain to assess the effect of sustained
      long-term central expression of leptin on immune responses. The rAAV-leptin rats
      had elevated central leptin over the 60 day duration of the experiment, whereas
      body fat and circulating leptin fell to near zero levels. The DTH response was
      significantly reduced by 10-20% in rats receiving rAAV-leptin compared with the
      control rats, and the difference was maintained for over 50 h. When the rats
      undergoing rAAV-leptin gene therapy were given either murine recombinant leptin
      or PBS s.c., rats receiving leptin had a 17% higher DTH response than rats
      receiving PBS. The isolated splenocytes from the former group also proliferated
      34% more in vitro in response to the mitogen concanavalin A as compared with the
      latter group. These results suggest that peripheral leptin has a dominant role in
      maintaining T-cell-mediated immune responses in rats, and central leptin is
      unable to compensate for the immunosuppression associated with peripheral
      hypoleptinemia. Furthermore, preservation of normal cell-mediated immune
      responses does not require fat tissue as along as serum leptin levels are
      maintained.

PMID- 12208667
TI  - Postnatal changes in ghrelin mRNA expression and in ghrelin-producing cells in
      the rat stomach.
AB  - Ghrelin was recently isolated from the rat stomach as an endogenous ligand for
      the GH secretagogue receptor. Although it is well known that a large amount of
      ghrelin is produced in the gastrointestinal tract, developmental changes in
      ghrelin mRNA expression and differentiation of ghrelin-immunopositive (ghrelin
      ip) and mRNA-expressing (ghrelin-ex) cells in the stomach have not been
      elucidated. In this study, we therefore investigated the changes in ghrelin mRNA
      expression levels and in the numbers of ghrelin-ip and -ex cells in the stomachs
      of 1- to 8-week-old male and female rats by Northern blot analysis,
      immunohistochemistry and in situ hybridization. Northern blot analysis showed
      that the level of weak ghrelin mRNA expression was low in the postnatal period
      but then increased in a dimorphic pattern, i.e. transient stagnation at 4 weeks
      in the male rats and at 5 weeks in the female rats. The number of ghrelin-ip and
      ghrelin-ex cells also increased after birth, and more numerous ghrelin cells were
      found in female rats than in male rats, and this finding was confirmed by
      Northern blot analysis. Ghrelin-ip and -ex cells first appeared in the glandular
      base of the fundic gland and then they were found in the glandular base and the
      glandular neck at 3 weeks of age, suggesting that the distribution of ghrelin
      cells is extended from the glandular base to the glandular neck during the
      postneonatal development period. This is the first report on detailed changes in
      postneonatal ghrelin expression level and in the number of ghrelin cells in the
      rat stomach. The sexual dimorphism of ghrelin expression and ghrelin cell
      differentiation suggest that ghrelin plays an important physiological role in the
      stomach.

PMID- 12208668
TI  - Influence of steroids and GnRH on biosynthesis and secretion of secretogranin II
      and chromogranin A in relation to LH release in LbetaT2 gonadotroph cells.
AB  - The granin proteins secretogranin II (SgII) and chromogranin A (CgA) are commonly
      found associated with LH and/or FSH within specialised secretory granules in
      gonadotroph cells, and it is possible that they play an important role in the
      differential secretion of the gonadotrophins. In this study we have examined the
      regulation of the biosynthesis and secretion of SgII and CgA, in relation to LH
      secretion, in the LbetaT2 mouse pituitary gonadotroph cell line. Three
      experiments were carried out to investigate the effects of oestradiol (E2) and
      dexamethasone (Dex) in the presence and absence of GnRH (experiment 1), differing
      GnRH concentrations (experiment 2) and alterations in GnRH pulse frequency
      (experiment 3). In experiment 1, exposure to E2, Dex or E2+Dex, either with or
      without GnRH treatment, resulted in increased LH secretion. Steroids alone had no
      effect on LHbeta mRNA levels, but in the presence of GnRH LHbeta mRNA levels were
      increased in Dex- and E2+Dex-treated cells. GnRH receptor (GnRH-R) mRNA levels
      were up-regulated by Dex and E2+Dex, but were unaffected by GnRH. There were no
      steroid-induced changes in SgII or CgA mRNA, but increased levels of CgA mRNA
      were observed after GnRH treatment in cells cultured in the presence of Dex. In
      experiment 2, increasing concentrations of GnRH resulted in increases in LH
      secretion that were inversely dose-dependent. No changes in LHbeta, GnRH-R or
      SgII mRNA levels were observed, but there were dose-dependent increases in CgA
      mRNA levels. In experiment 3, GnRH was given as either 1 pulse/day or 4
      pulses/day for 3 days. Both pulse regimes resulted in increased LH, SgII and CgA
      secretion compared with controls during the first 15 min pulse on day 3. Exposure
      to GnRH at 4 pulses/day increased LH and SgII secretion compared with controls
      during all 4 pulses, but secretion of both proteins was reduced during pulses 2-4
      compared with pulse 1. CgA secretion also increased due to GnRH in pulse 1, but
      was decreased by GnRH treatment during pulse 2, and unchanged by GnRH during
      pulses 3 and 4. Total daily secretion of LH and SgII from cells given 1 pulse/day
      of GnRH increased compared with controls on all three treatment days, while total
      CgA secretion increased in response to GnRH on days 2 and 3 only. Intracellular
      levels of SgII, but not LH, decreased after GnRH treatment. In contrast,
      intracellular CgA was increased, but only after 4 pulses/day of GnRH. Levels of
      LHbeta, but not SgII, mRNA were increased by both pulse regimes, while CgA mRNA
      levels increased after 1 pulse/day of GnRH. These results indicate that there is
      a close correlation between the GnRH-stimulated release of LH and SgII from
      LbetaT2 cells, suggesting that SgII may have an influential role in the regulated
      secretion of LH, possibly by inducing LH aggregation to facilitate trafficking
      into secretory granules. CgA secretion does not appear to be closely associated
      with that of LH, but CgA expression does appear to be regulated by GnRH, which
      may indicate involvement in the control of LH secretion, possibly by influencing
      the proportion of LH in the different types of secretory granules.

PMID- 12208669
TI  - Gonadotropin-induced expression of pancreatitis-associated protein-III mRNA in
      the rat ovary at the time of ovulation.
AB  - The ovulatory process in mammals involves gross physiological events in the ovary
      that cause transient deterioration of the ovarian connective tissue and rupture
      of the apical walls of mature follicles. This gonadotropin-induced process has
      features similar to an acute inflammatory reaction that affects most of the
      ovary. The present study reveals that the ovulatory events include induction of
      mRNA for pancreatitis-associated protein-III (PAP-III). Immature Wistar rats were
      primed with 10 IU equine chorionic gonadotropin s.c., and 48 h later the 12-h
      ovulatory process was initiated by 10 IU human chorionic gonadotropin (hCG) s.c.
      Ovarian RNA was extracted at 0, 2, 4, 8, 12 and 24 h after the animals were
      injected with hCG. The RNA extracts were used for RT-PCR differential display to
      detect PAP-III gene expression in the stimulated ovarian tissue. Northern
      blotting showed that transcription was significantly greater at 4-12 h after the
      ovaries had been stimulated by hCG. In situ hybridization indicated that PAP-III
      mRNA expression was limited mainly to the hilar region of the ovarian stroma,
      with most of the signal emanating from endothelial cells that lined the inner
      walls of blood vessels, and from small secondary follicles. Treatment of the
      animals with ovulation-blocking doses of indomethacin (an inhibitor of prostanoid
      synthesis) or epostane (an inhibitor of progesterone synthesis) revealed that
      ovarian transcription of PAP-III mRNA was moderately dependent on ovarian
      progesterone synthesis. In conclusion, the present evidence of an increase in PAP
      III gene expression in gonadotropin-stimulated ovaries provides further evidence
      that the ovulatory process is comparable to an inflammatory reaction.

PMID- 12208670
TI  - Corticotrophin-releasing hormone inhibits insulin-like growth factor-I release
      from primary cultures of rat granulosa cells.
AB  - Corticotrophin-releasing hormone (CRH), a neuropeptide which modulates gonadal
      function during stress, is expressed by several cell types of the rat ovary and
      is able to suppress oestrogen release from rat granulosa cells. The mechanism of
      this effect is, however, not known. Since insulin-like growth factor (IGF)-I is
      produced by rat granulosa cells and exerts a synergistic role with FSH on
      granulosa cell steroidogenesis, we hypothesised that CRH may suppress oestrogen
      release from granulosa cells by inhibiting IGF-I release and/or stimulating the
      release of its binding protein (IGFBP-3). To test this hypothesis, granulosa
      cells were obtained from immature female Sprague-Dawley rats primed with
      diethylstilboestrol, and hormone concentrations were measured in the conditioned
      medium by radioimmunoassay. CRH suppressed oestrogen and IGF-I release stimulated
      by FSH used at a concentration of 1 IU/l, whereas it did not have any
      statistically significant effect on oestrogen and IGF-I release in basal
      conditions or in response to 5 IU/l FSH. The suppressive effects of CRH on
      oestrogen and IGF-I release were antagonised by a selective CRH receptor
      antagonist. CRH had no effects on IGFBP-3 release. CRH did not have any effect on
      oestrogen release stimulated by increasing concentrations of IGF-I and its
      suppressive effect on FSH-stimulated oestrogen release was overcome by the
      addition of low doses of exogenous IGF-I. In conclusion, CRH suppressed the
      release of oestrogen and IGF-I, but not of IGFBP-3. Thus, the inhibitory effects
      of CRH on oestrogen release could be mediated, partly, by a suppression of the
      autocrine/paracrine action of IGF-I.

PMID- 12208671
TI  - Insulin and IGF-I are necessary for FSH-induced cytochrome P450 aromatase but not
      cytochrome P450 side-chain cleavage gene expression in oestrogenic bovine
      granulosa cells in vitro.
AB  - The earliest biochemical indicators of ovarian follicle deviation in cattle
      include lower oestradiol and free IGF concentrations in subordinate compared with
      dominant follicles. We determined if decreases in FSH, IGF-I or insulin cause
      decreased P450 aromatase (P450arom) or P450 cholesterol side-chain cleavage
      (P450scc) mRNA expression in oestrogenic bovine granulosa cells in vitro. In the
      first experiment, cells obtained from small follicles (2-5 mm diameter) were
      cultured in serum-free medium supplemented with physiological concentrations of
      FSH, IGF-I and insulin for 4 days. A decrease in specific hormone concentration
      was produced by replacing 70% of spent medium with medium devoid of FSH, insulin,
      or insulin and IGF-I on day 4 and again on day 5 of culture. Cultures were
      terminated on day 7. A reduction in FSH concentrations during the last 3 days of
      culture decreased P450arom and P450scc mRNA levels. A reduction in insulin
      reduced P450arom but not P450scc mRNA levels, and a reduction of both insulin and
      IGF-I concentrations further decreased P450arom mRNA levels and decreased P450scc
      mRNA levels. In a second experiment, cells obtained from small follicles (2-5 mm
      diameter) were cultured with insulin (100 ng/ml) without FSH for 4 days, and then
      insulin was withdrawn from the culture and FSH added for a further 3 days. The
      withdrawal of insulin decreased (P<0.02) oestradiol accumulation and reduced
      P450arom mRNA to below detectable levels, but did not affect P450scc mRNA levels.
      The addition of FSH transiently increased oestradiol secretion and P450arom mRNA
      levels, but P450arom mRNA levels were undetectable at the end of the culture
      period. The addition of FSH significantly enhanced P450scc mRNA levels and
      progesterone accumulation. These data demonstrated that a reduction of insulin
      like activity reduced aromatase gene expression in bovine follicles without
      necessarily affecting progesterone synthetic capability, and thus may initiate
      follicle regression in cattle at the time of follicle divergence.

PMID- 12208672
TI  - Clodronate inhibits adrenocortical cell proliferation and P450c21 activity.
AB  - Bisphosphonates (BPs), specific inhibitors of osteoclasts, are well established
      in the management of skeletal metastases in breast cancer. Recent studies have
      suggested that these compounds may also directly influence tumor cell
      proliferation. As adrenocortical cancer frequently leads to bone metastases, we
      investigated the effects of clodronate (CLO) in the human adrenocortical cancer
      cell line NCI-H295 and in primary cultures of bovine adrenocortical cells. Both
      the non-amino BP CLO and the amino BP pamidronate (PAM) exhibited a dose
      dependent antiproliferative effect in both cell types (cell viability in NCI-H295
      cells: 100 microM CLO: 98+/-8%; 500 microM CLO 76+/-6%; 1000 microM CLO 53+/-2;
      10 microM PAM 96+/-3%; 50 microM PAM 46+/-6%; 100 microM PAM 11+/-1% vs untreated
      control cells: 100+/-10%; P<0.01). FACS analysis in NCI-H295 cells treated with
      either CLO or PAM demonstrated both apoptotic and necrotic cell death. However,
      while during PAM treatment cell number and hormone secretion decreased in
      parallel, we observed specific impairment of steroidogenesis in the presence of
      CLO with a dose-dependent increase in the 17-OH-progesterone/cortisol ratio (100
      microM CLO 134+/-30%; 500 microM CLO 284+/-10%; 1000 microM CLO 545+/-130% vs
      100+/-20% in control cells; P<0.01). Further analysis in ACTH-stimulated bovine
      adrenal cells using stable isotope dilution/gas chromatography-mass spectrometry
      demonstrated CLO-induced inhibition of adrenal 21-hydroxylase (P450c21) activity
      leading to a dose-dependent increase in the 17-OH-progesterone/11-deoxycortisol
      ratio. In conclusion, we demonstrate a dose-dependent antiproliferative effect of
      CLO and PAM in adrenocortical cells. In addition, for the first time, we describe
      a suppressive effect of CLO on steroidogenesis via inhibition of adrenal 21
      hydroxylase (P450c21) activity.

PMID- 12208673
TI  - Differential expression of IgG Fc binding protein (FcgammaBP) in human normal
      thyroid tissue, thyroid adenomas and thyroid carcinomas.
AB  - The genetic events involved in thyroid carcinogenesis are still incompletely
      understood. Several rearrangements and mutations of oncogenes have been
      implicated in the development of thyroid papillary carcinomas, follicular
      adenomas and carcinomas. However, none of these molecular alterations is suitable
      either as a general marker for the diagnosis of thyroid carcinomas or to
      differentiate between thyroid follicular adenomas and carcinomas. In order to
      identify new genes with altered expression which could serve as such markers, we
      analyzed RNA from thyroid tumor and normal tissue using a novel technique called
      restriction-mediated differential display. Several differentially expressed genes
      were identified, including the gene for IgG Fc binding protein (FcgammaBP).
      Differential expression of FcgammaBP was confirmed by quantitative real-time RT
      PCR. Our experiments showed that IgG Fc binding protein (FcgammaBP) is
      differentially expressed in normal thyroid tissue, thyroid adenomas and thyroid
      carcinomas. While the FcgammaBP gene is constitutively expressed in normal
      thyroid tissue, its expression is significantly increased in follicular thyroid
      adenomas and significantly decreased in papillary and follicular thyroid
      carcinomas. Thus, measurement of the expression levels of FcgammaBP in thyroid
      biopsies might help to make the otherwise difficult distinction between a thyroid
      follicular adenoma and a follicular carcinoma.

PMID- 12208674
TI  - Liver receptor homologue-1 is expressed in human steroidogenic tissues and
      activates transcription of genes encoding steroidogenic enzymes.
AB  - In the current study we test the hypothesis that liver receptor homologue-1 (LRH;
      designated NR5A2) is involved in the regulation of steroid hormone production.
      The potential role of LRH was assessed by first examining expression in human
      steroidogenic tissues and second by examining effects on transcription of genes
      encoding enzymes involved in steroidogenesis. LRH is closely related to
      steroidogenic factor 1 (SF1; designated NR5A1), which is expressed in most
      steroidogenic tissues and regulates expression of several steroid-metabolizing
      enzymes. LRH transcripts were expressed at high levels in the human ovary and
      testis. Adrenal and placenta expressed much lower levels of LRH than either ovary
      or liver. To examine the effects of LRH on steroidogenic capacity we used
      reporter constructs prepared with the 5'-flanking region of steroidogenic acute
      regulatory protein (StAR), cholesterol side-chain cleavage (CYP11A1), 3beta
      hydroxysteroid dehydrogenase type II (HSD3B2), 17alpha hydroxylase, 17,20 lyase
      (CYP17), 11beta hydroxylase (CYP11B1) and aldosterone synthase (CYP11B2). Co
      transfection of these reporter constructs with LRH expression vector demonstrated
      that like SF1, LRH enhanced reporter activity driven by flanking DNA from StAR,
      CYP11A1, CYP17, HSD3B2, and CYP11B1. Reporter constructs driven by CYP11A1 and
      CYP17 were increased the most by co-transfection with LRH and SF1. Of the
      promoters examined only HSD3B2 was more sensitive to LRH than SF1. The high level
      of ovarian and testicular LRH expression make it likely that LRH plays an
      important role in the regulation of gonadal function.

PMID- 12208675
TI  - A randomized controlled trial of mist in the acute treatment of moderate croup.
AB  - OBJECTIVE: To determine whether the use of mist improves clinical symptoms in
      children presenting to the emergency department (ED) with moderate croup.
      METHODS: Children 3 months to 6 years of age were eligible for the study if they
      presented to the ED with moderate croup. Moderate croup was defined as a croup
      score of 2-7. The patients were randomly assigned to receive either mist
      (humidified oxygen) via mist stick or no mist. The patients had croup scores
      measured at baseline and every 30 minutes for up to two hours. At these intervals
      the following parameters were also measured: heart rate, respiratory rate, oxygen
      saturation, and patient comfort score. The patients were treated until the croup
      score was less than 2 or until two hours had elapsed. All patients initially
      received a dose of oral dexamethasone (0.6 mg/kg). Other treatments, such as
      racemic epinephrine or inhaled budesonide, were given at the discretion of the
      treating physician. The research assistants were unaware of the assigned
      treatments. RESULTS: There were 71 patients enrolled in the study; 35 received
      mist and 36 received no mist. The two treatment groups had similar
      characteristics at baseline. The median baseline croup score was 4 in both
      groups. The outcomes were measured as the change from baseline at 30, 60, 90, and
      120 minutes. The change in the croup score from baseline in the mist group was
      not statistically different from the croup score change in the group that did not
      receive mist (p = 0.39). There was also no significant difference in improvement
      of oxygen saturation, heart rate, or respiratory rate at any of the assessment
      times. There was no adverse effect from the mist therapy. CONCLUSIONS: Mist
      therapy is not effective in improving clinical symptoms in children presenting to
      the ED with moderate croup.

PMID- 12208676
TI  - Emergency department triage of patients infected with HIV.
AB  - OBJECTIVE: The emergency department (ED) and HIV specialty clinics are primary
      sources of care for persons infected with HIV. HIV disease may be complicated by
      vague and complex symptomatology, and determining the degree of illness at triage
      is often difficult. The goals of this project were to characterize the ED
      presentation of HIV-related conditions, to develop a clinical decision rule to
      triage HIV-infected patients, and to validate the rule in clinical practice.
      METHODS: The study population consisted of ambulatory patients with self-reported
      HIV infection who presented for care to the ED of a 553-bed public hospital that
      serves a medically indigent, minority population. An Illness Severity Instrument
      was developed by an expert panel to serve as the criterion standard for defining
      medical urgency for HIV-infected patients presenting to the ED for care. Two
      phases of the study were conducted. Data from the first phase, a
      noninterventional cohort study, were used to develop a clinical decision rule for
      the ED triage of HIV-infected patients. The second phase was a prospective
      validation of the clinical decision rule. RESULTS: During phase I, data from 542
      patient visits were collected. Data from 441 (81%) patient visits were used in a
      classification and regression tree (CART) analysis to produce a decision rule,
      the Clinical Triage Instrument. During phase II, the prospective validation of
      the Clinical Triage Instrument, 156 patient visits occurred. Of these, 88 (56%)
      patient visits were triaged using the Clinical Triage Instrument and could be
      scored using the Illness Severity Instrument. The Clinical Triage Instrument
      accurately triaged 45 [51%; 95% confidence interval (95% CI) = 40% to 62%]
      patient visits, undertriaged 11 (13%; 95% CI = 6% to 21%) patient visits, and
      overtriaged 32 (36%; 95% CI = 26% to 47%) patient visits. Sensitivities and
      specificities for determining emergent, urgent, and nonurgent medical conditions
      by the Clinical Triage Instrument were 56% (95% CI = 31% to 75%) and 84% (95% CI
      = 74% to 92%), 71% (95% CI = 55% to 84%) and 39% (95% CI = 25% to 55%), and 18%
      (95% CI = 6% to 37%) and 93% (95% CI = 84% to 98%), respectively. The positive
      and negative predictive values for determining an emergent medical condition
      using the Clinical Triage Instrument were 48% (95% CI = 26% to 70%) and 88% (95%
      CI = 78% to 95%), respectively. The positive and negative predictive values for
      determining a nonurgent medical condition using the Clinical Triage Instrument
      were 56% (95% CI = 21% to 86%) and 71% (95% CI = 60% to 81%), respectively.
      CONCLUSIONS: The Clinical Triage Instrument was not sufficiently accurate for
      clinical use. Until accurate and reliable triage methods are developed, all
      patients infected with HIV who present to the ED for care should receive timely
      evaluation and care.

PMID- 12208677
TI  - Predictive validity of the Global Assessment Form used in a final-year
      undergraduate rotation in emergency medicine.
AB  - OBJECTIVES: To determine whether the predictive validity of Global Assessment
      Form (GAF) knowledge subdomain marks exceeds that of the overall GAF marks with
      respect to written examination marks for an undergraduate rotation in emergency
      medicine, and to determine the interdependence between subdomain marks on the
      GAF. METHODS: Final-year clinical clerks completing a four-week rotation through
      the emergency departments of a university teaching center were evaluated using
      both a ten-subdomain GAF for clinical performance and an independent written
      examination. The GAF and examination marks were prospectively obtained for
      clinical clerks over a two-year period. Pearson correlations were calculated
      between examination marks and both the GAF knowledge subdomain and the GAF
      overall mark. Olkin's Z score was calculated to determine the significance of the
      difference between correlations. Interdependencies between subdomains of the GAF
      were calculated using an alpha coefficient and inter-item correlations. RESULTS:
      Data sets were reviewed for 347 clinical clerks. Nine sets of data were excluded
      (incomplete evaluations); 338 sets were analyzed. Means for overall clinical mark
      and examination mark were 80.11% (SD = 4.375) and 81 (SD = 7.66). Among
      subdomains, knowledge had the highest correlation with the examination mark
      (0.19). Overall clinical marks had lower correlation with the examination marks
      (0.169); the difference was not significant (Olkin's Z = 0.40). The correlation
      of the examination marks with the average marks of all subdomains excluding
      knowledge was even lower (0.12). The tenitem alpha for the GAF was 0.92.
      CONCLUSIONS: Clinical GAF assessments of knowledge, as measured by written
      examination, do not appear to be any more predictive than overall clinical
      impression. There is substantial consistency between subdomain scores, suggesting
      that assessors are not effectively discriminating between them when assigning
      marks.

PMID- 12208678
TI  - Adverse cardiac events in emergency department patients with chest pain six
      months after a negative inpatient evaluation for acute coronary syndrome.
AB  - OBJECTIVE: To evaluate the impact of the diagnostic test setting-inpatient versus
      outpatient-on adverse cardiac events (ACEs) after six months in emergency
      department (ED) patients with chest pain who were admitted to the hospital and
      subsequently had a negative evaluation for acute coronary syndrome (ACS).
      METHODS: The authors retrospectively studied a consecutive sample of ED patients
      with chest pain over a nine-month period. All patients were admitted to the
      hospital and underwent negative evaluations for ACS, defined as the absence of
      diagnostic changes on serial electrocardiograms or cardiac markers (creatine
      kinase-MB and troponin T), and a negative diagnostic cardiac study. Subjects were
      classified according to cardiac diagnostic study setting-either inpatient or
      outpatient. Diagnostic testing included exercise treadmill, angiography, stress
      echocardiography, or stress thallium scans. Acute cardiac events at six months
      were defined as cardiac death, myocardial infarction, unstable angina, cardiac
      arrest, or emergent revascularization. RESULTS: The six-month rate of ACEs among
      157 subjects was 14%, with 2% cardiac mortality. The outpatient group had higher
      ACE risk when compared with the inpatient group using multivariate logistic
      regression, both for the entire cohort (OR 3.5, p < 0.03) and for a subgroup
      excluding patients with prior coronary artery disease (OR 6.7, p < 0.05). The
      outpatient group included 19 of 52 (37%) noncompliant subjects who did not
      receive a diagnostic study. CONCLUSIONS: Long-term cardiac morbidity of patients
      after a negative ACS evaluation may be higher than previously thought. Risk of
      ACE is significantly higher in subjects scheduled for outpatient diagnostic
      tests. Inpatient diagnostic testing is justified for subjects at risk for poor
      compliance.

PMID- 12208679
TI  - Congestive heart failure patients with chest pain: incidence and predictors of
      acute coronary syndrome.
AB  - OBJECTIVE: New diagnostic and treatment options for emergency department (ED)
      patients with congestive heart failure (CHF) may facilitate the ED discharge of
      some patients. However, some patients require admission to exclude concurrent
      acute coronary syndrome (ACS) as the precipitant of CHF. The objective of this
      study was to identify the incidence, clinical characteristics, and hospital
      course of CHF patients who present to the ED with and without concurrent ACS.
      METHODS: This was a prospective cohort study of consecutive patients >23 years of
      age who presented to the ED with chest pain, received an electrocardiogram (ECG),
      and either had a known history of CHF or presented with new-onset CHF, between
      July 1999 and April 2001. The hospital course of each patient was followed daily,
      and telephone follow-up occurred at 30 days. The main outcomes were the incidence
      of ACS and comparisons of lengths of hospital stay (LOSs), rates of admission to
      the intensive care unit (ICU), intubations, and death rates among patients with
      and without ACS. RESULTS: Two hundred ninety-eight CHF patients presented 380
      times. The incidence of ACS in the 380 patient visits was 32% (95% CI = 27% to
      36%). Compared with patients who did not have ACS, patients who had concurrent
      ACS were more likely to have known coronary artery disease (CAD) (67% vs. 42%; p
      < 0.0001) and hypercholesterolemia (36% vs. 18%; p = 0.0002). Patients with
      concurrent ACS were also more likely to be admitted to the hospital (97% vs 82%;
      p < 0.0001), had a longer LOS (5.2 [3.9-6.5] vs 3.2 [2.6-3.8] days; p = 0.006),
      had higher rates of ICU admission (44% vs. 13%; p < 0.0001), were more likely to
      be intubated (8% vs. 1%, p = 0.002), and were more likely to die (15 vs 7 deaths;
      p < 0.0001). CONCLUSIONS: The incidence of ACS in ED CHF patients with chest pain
      was 32%. Patients with CHF complicated by ACS had more prolonged hospital stays,
      required higher levels of care, and had a higher incidence of death than those
      patients without ACS. Strategies tailored to early identification and management
      of these patients would be desirable.

PMID- 12208680
TI  - Lack of association between patient ethnicity or race and fracture analgesia.
AB  - OBJECTIVE: Ethnic and racial differences in the provision of emergency department
      (ED) analgesia for long-bone fractures have recently been reported in two large
      cities. The authors sought to determine, in a third city, whether nonwhite
      patients with long-bone fractures were less likely to receive analgesics than
      white patients with similar injuries. METHODS: At an urban Level 1 trauma center
      and teaching hospital, a retrospective cohort study was conducted of all ED
      patients aged 18 to 55 years seen from July 1, 1998, through June 30, 1999, with
      an ED discharge diagnosis of isolated long-bone fracture identified by ICD-9
      codes 812, 813, 821, and 823. Exclusion criteria included injury more than 12
      hours prior to presentation or a Glasgow Coma Scale score of less than 14. The
      main outcome measure was ED analgesia administration. RESULTS: Three hundred
      twenty-three patients met inclusion criteria; 181 were white, 58 African
      American, 46 Hispanic, 38 Asian. All ethnic/racial groups were equally likely to
      receive no analgesia or no parenteral analgesia. The overall risk for no
      analgesia was 20% and for no parenteral analgesia was 31%. Stratification and
      multiple logistic regression to control for gender, bone fractured, and need for
      reduction failed to identify any trend toward reduced analgesia administration in
      any ethnic/racial group. CONCLUSIONS: In contrast to two recently reported
      studies, at this urban trauma center and teaching hospital ED, there was no
      difference in the administration of analgesics to white and nonwhite patients
      with long-bone fractures.

PMID- 12208681
TI  - Usual source of care and nonurgent emergency department use.
AB  - OBJECTIVE: To examine whether dissatisfaction with one's usual source of care
      (USC) and perceived access difficulties to one's USC were associated with
      nonurgent emergency department (ED) use. METHODS: Variables that measured USC
      satisfaction and access were identified in the 1996 cohort of the Medical
      Expenditure Panel Survey (MEPS), a nationally representative sample administered
      by the Agency for Healthcare Research and Quality. The main outcome measured was
      nonurgent ED use at least once during 1996. RESULTS: A total of 9,146 adults had
      a USC other than the ED, had at least one contact with the health care system or
      were unable to get needed care, and had complete data for all the variables in
      the final model. Dissatisfaction with the USC, dissatisfaction with the USC
      staff, lack of confidence in the USC's ability, difficulty scheduling an
      appointment, difficulty reaching the USC by phone, and long waiting times with an
      appointment were all associated with having a nonurgent ED visit in 1996 (all at
      p < 0.05). The positive associations between both dissatisfaction and perceived
      access barriers and nonurgent ED use persisted even in multiple logistic
      regression that adjusted for age, sex, race, education, health status, employment
      status, income, insurance, region of residence, and rural vs. urban residence.
      CONCLUSIONS: Patients who are dissatisfied with their USC or perceive access
      barriers to their USC are more likely to have a nonurgent ED visit.

PMID- 12208682
TI  - Crash scene photography in motor vehicle crashes without air bag deployment.
AB  - OBJECTIVE: To determine whether vehicle characteristics, measured using crash
      scene photography, are associated with anatomic patterns of injury and severity
      of injury sustained in motor vehicle crashes (MVCs) without air bag deployment.
      METHODS: A prospective observational study was conducted over 22 months, using 12
      fire departments serving two hospitals. Two vehicle photographs (exterior and
      interior) were taken at each MVC. Vehicular variables were assigned by grading
      the photographs with a standardized scoring system, and outcome information on
      each patient was collected by chart review. RESULTS: Five hundred fifty-nine
      patients were entered into the study. Frontal crashes and increasing passenger
      space intrusion (PSI) were associated with head, facial, and lower-extremity
      injuries, while rear crashes were associated with spinal injuries. Restraint use
      had a protective effect in head, facial, and upper and lower extremity injuries,
      yet was associated with higher odds of spinal injury. Lack of restraint use,
      increasing PSI, and steering wheel deformity were associated with an increased
      hospital length of stay and hospital charges, yet only steering wheel deformity
      was associated with increasing injury severity when adjusting for other crash
      variables. CONCLUSIONS: Out-of-hospital variables, as obtained from crash vehicle
      photography, are associated with injury site, injury severity, hospital length of
      stay, and hospital charges in patients involved in MVCs without air bag
      deployment.

PMID- 12208683
TI  - Window to the soul.

PMID- 12208684
TI  - Bench to bedside: brain edema and cerebral resuscitation: the present and future.
AB  - Sudden cardiac arrest (CA) claims approximately 1,200 lives daily in the United
      States. Cardiopulmonary resuscitation attempts have so far achieved suboptimal
      results, and even when restoration of spontaneous circulation (ROSC) is achieved,
      about 30% of survivors suffer permanent brain damage. This illustrates the need
      for an improved basic scientific understanding of the pathophysiology of global
      cerebral injury caused by whole-body ischemia/reperfusion (I/R) injury following
      CA. Brain edema has been recently documented in experimental CA followed by one
      hour of ROSC. Brain edema has also been documented in CA and stroke patients by
      computed tomography or magnetic resonance imaging scanning, and has been shown to
      predict a poor neurologic outcome. The mechanisms underlying brain edema
      formation elicited by CA are unclear. New scientific findings of the roles of
      blood-brain barrier (BBB) permeability, matrix metalloproteinases (MMPs) of a
      family of proteases, aquaporin 4 (AQP4) of a family of membrane water-channel
      proteins, and the N-methyl-D-aspartate (NMDA) receptors in the mechanisms
      underlying CA-elicited brain edema were reviewed. By defining the roles of BBB
      permeability, MMPs, AQP4, and NMDA receptors in CA-induced brain edema formation,
      effective new therapeutic strategies to extend cellular and tissue survival, and
      preserve neurologic function following CA may be feasible.

PMID- 12208685
TI  - Emergency medicine: competencies for youth violence prevention and control.
AB  - By any standard one wishes to apply, the impact of violence on the health and
      safety of the public is significant. The expression of violence among children in
      the United States has increased significantly during the modern era. Homicide and
      suicide are the second and third leading causes of death in youths 15-24 years of
      age. The emergency department (ED) is a common site for the care of these
      victims, and because victims often become assailants, the emergency care provider
      needs to know the epidemiology, treatment, and methods for prevention of youth
      violence in order to curtail the cycle. A multidisciplinary task force was
      convened by the Centers for Disease Control and Prevention (CDC)-funded Southern
      California Center of Academic Excellence on Youth Violence Prevention and the
      Keck School of Medicine at the University of Southern California to define
      competencies for health professionals in youth violence prevention and control.
      Three levels of competence were identified: the generalist level, which should be
      obtained by all health professionals; the specialist level, which should be
      obtained by health professionals such as emergency medicine providers, who
      frequently work with populations affected by violence; and a third, or scholar
      level, to be acquired by health professionals who wish to become experts not only
      in the care, but also in research and advocacy. This article reports the details
      of this group's efforts and applies them to emergency care provider education.
      These competencies should shape the development of curricula for the span of
      emergency medical training from emergency medical services scholastic training to
      postgraduate continuous medical education.

PMID- 12208686
TI  - A comparison of the antemortem clinical diagnosis and autopsy findings for
      patients who die in the emergency department.
AB  - OBJECTIVES: In spite of advances in medical technology, there remains a high
      discrepancy rate between the antemortem clinical diagnosis and postmortem
      examination diagnosis for patients who die in hospitals. The aim of this study
      was to compare the clinical and postmortem examination diagnoses of patients who
      died in the emergency department (ED) of a tertiary hospital, and to analyze any
      discrepancy between them. METHODS: The study was a retrospective chart review of
      patients who died in the ED of a tertiary referral teaching hospital and a
      comparison of the antemortem diagnosis with the autopsy diagnosis. Any missed
      diagnosis was classified, according to the Goldman criteria, into major and minor
      missed diagnoses. RESULTS: A total of 59 patients were eligible for inclusion in
      the study. There was complete agreement between the antemortem diagnosis and the
      autopsy result in 51% of cases. The incidence of major missed diagnoses-where if
      the diagnosis had been known before the patient died, treatment may have been
      altered or survival may have been prolonged-was 7%. CONCLUSIONS: There is a
      significant discrepancy rate between the antemortem diagnosis and the autopsy
      diagnosis. However, in this study, serious missed diagnoses in which outcome may
      have been significantly altered are unusual among those who die in the ED of a
      tertiary referral hospital.

PMID- 12208687
TI  - Rapid opioid detoxification in Australia.

PMID- 12208688
TI  - Rapid opioid detoxification in Australia.

PMID- 12208689
TI  - Induced hypothermia for drug overdose.

PMID- 12208690
TI  - Psychiatric perspectives on medical screening of psychiatric patients.

PMID- 12208691
TI  - Competition in health care.

PMID- 12208692
TI  - Update on childhood esotropia.

PMID- 12208694
TI  - Trabeculectomy and angle closure.

PMID- 12208696
TI  - Accommodation measurement in presbyopes.

PMID- 12208697
TI  - OAG in Barbados.

PMID- 12208698
TI  - Pediatric DCR for nasolacrimal duct obstruction.

PMID- 12208702
TI  - Error tolerance in helmholtzian accommodation.

PMID- 12208703
TI  - Argon laser peripheral iridoplasty versus conventional systemic medical therapy
      in treatment of acute primary angle-closure glaucoma : a prospective, randomized,
      controlled trial.
AB  - OBJECTIVE: To study whether argon laser peripheral iridoplasty (ALPI) is as
      effective and safe as conventional systemic medications in treatment of acute
      primary angle-closure glaucoma (PACG) when immediate laser peripheral iridotomy
      is neither possible nor safe. DESIGN: Prospective, randomized, controlled trial.
      PARTICIPANTS: Seventy-three eyes of 64 consecutive patients with their first
      presentation of acute PACG, with intraocular pressure (IOP) levels of 40 mmHg or
      more, were recruited into the study. INTERVENTION: The acute PACG eye of each
      consenting patient received topical pilocarpine (4%) and topical timolol (0.5%).
      The patients were then randomized into one of two treatment groups. The ALPI
      group received immediate ALPI under topical anesthesia. The medical treatment
      group was given 500 mg of intravenous acetazolamide, followed by oral
      acetazolamide 250 mg four times daily, and an oral potassium supplement until IOP
      levels normalized. Intravenous mannitol also was administered to the latter group
      if the presenting IOP was higher than 60 mmHg. The acute PACG eye of both groups
      continued to receive topical pilocarpine (1%) until peripheral iridotomy could be
      performed. MAIN OUTCOME MEASURES: Intraocular pressure profile, corneal clarity,
      symptoms, visual acuity, angle status by indentation gonioscopy, and
      complications of treatment. RESULTS: Thirty-three acute PACG eyes of 32 patients
      were randomized to receive immediate ALPI, whereas 40 acute PACG eyes of 32
      patients had conventional systemic medical therapy. Both treatment groups were
      matched for age, duration of attack, and IOP at presentation. The ALPI-treated
      group had lower IOP levels than the medically treated group at 15 minutes, 30
      minutes, and 1 hour after the start of treatment. The differences were
      statistically significant. The difference in IOP levels became statistically
      insignificant from 2 hours onward. The duration of attack did not affect the
      efficacy of ALPI in reducing IOP in acute PACG. No serious laser complications
      occurred, at least in the early postlaser period. CONCLUSIONS: Argon laser
      peripheral iridoplasty significantly is more effective than conventional systemic
      medications in reducing IOP levels in acute PACG in eyes not suitable for
      immediate laser peripheral iridotomy within the first 2 hours from the initiation
      of treatment. Argon laser peripheral iridoplasty is a safe and more effective
      alternative to conventional systemic medications in the management of acute PACG
      not amenable to immediate laser peripheral iridotomy.

PMID- 12208704
TI  - Primary phacoemulsification and intraocular lens implantation for acute angle
      closure glaucoma.
AB  - OBJECTIVE: To evaluate the safety and efficacy of primary phacoemulsification and
      intraocular lens implantation (PPI) for acute angle-closure glaucoma (ACG). STUDY
      DESIGN: Prospective, nonrandomized comparative trial. PARTICIPANTS AND
      INTERVENTION: Forty-three eyes of 43 patients with acute ACG and uncontrolled
      intraocular pressure (IOP) were treated by PPI. Thirty-two eyes of 32 patients
      treated by conventional surgical iridectomy (CSI) constituted the control group.
      MAIN OUTCOME MEASURES: Postoperative visual acuity, IOP, number of antiglaucoma
      medications, complications, and secondary surgical interventions, if any,
      required for IOP control. RESULTS: Glaucoma control was achieved in 31 eyes (72%)
      in the PPI group and in 11 (35%) in the CSI group (P = 0.01). Mean preoperative
      IOP was 40.5 +/- 7.6 mmHg (standard deviation) and 39.7 +/- 7.8 mmHg,
      respectively (P = 0.46). Mean postoperative IOP was 17.8 +/- 3.4 mmHg (PPI group)
      and 20.1 +/- 4.2 mmHg (CSI group) after a mean follow-up of 10.2 +/- 3.4 months
      (P = 0.03). Postoperatively, the mean number of ocular hypotensive medications
      was 0.18 +/- 0.45 (PPI group) and 0.45 +/- 0.62 (CSI group) (P = 0.0001).
      Relative increase in postoperative best-corrected visual acuity (logarithm of the
      minimum angle of resolution) was 0.52 +/- 0.29 (PPI group) and 0.19 +/- 0.21 (CSI
      group), respectively (P = 0.0001). Additional surgery was necessary in 5 eyes
      (11.5%) in the PPI group and in 20 eyes (63%) in the CSI group (P = 0.01).
      Intraoperative and postoperative complications were few and manageable.
      CONCLUSIONS: CSI in patients with acute ACG was effective in reducing IOP
      initially but was associated with multiple surgical reinterventions. Conversely,
      primary PPI turned out to be safe and effective in reducing IOP and improving
      visual acuity. These results affirm that lens extraction may be considered the
      better procedure in uncontrolled ACG when faced with options of CSI or PPI.

PMID- 12208705
TI  - Serial paracenteses in the management of acute elevations of intraocular
      pressure.
AB  - OBJECTIVE: To study the effectiveness of serial paracenteses in eyes with
      symptomatic elevated intraocular pressure (IOP). DESIGN: Retrospective,
      noncomparative, interventional case series. PARTICIPANTS: Five eyes of four
      patients with acute elevations in IOP. METHODS: A 5-year review of records was
      performed in one practice (LP) to identify patients who underwent more than one
      paracentesis for control of symptomatic increases in IOP when greater than 30
      mmHg. Five eyes of four patients were identified, and charts were analyzed for
      cause and duration of elevated pressure, control of symptoms associated with
      elevated pressure, number of paracenteses, and visual outcome. All patients
      received topical anesthetic (proparacaine 0.5%) before paracentesis, and topical
      ciprofloxacin, 0.35%, or tobramycin, 0.3%, before and after paracentesis, which
      was performed at the temporal limbus with a 0.75-mm sterile surgical blade.
      RESULTS: Paracentesis provided almost immediate symptomatic relief in all cases.
      The procedure could be repeated easily whenever symptoms recurred. The average
      number of paracenteses performed was three. No complications of paracentesis were
      noted. Visual outcomes were variable and dependent on the etiology of elevated
      IOP. Two eyes with neovascular glaucoma had poor visual outcomes. None of the
      other three eyes lost vision because of increased IOP. CONCLUSIONS: Acute
      symptomatic elevations of IOP in patients with a deep anterior chamber can be
      effectively treated with paracentesis. In selected cases, serial paracenteses may
      obviate the need for filtration surgery. If filtration surgery is required,
      serial paracenteses may allow it to be scheduled electively rather than
      emergently.

PMID- 12208706
TI  - Long-term filtration and visual field outcomes after primary glaucoma triple
      procedure with and without mitomycin-C.
AB  - OBJECTIVE: To evaluate the long-term effectiveness of glaucoma management in
      patients undergoing primary glaucoma triple procedure (PGTP) with and without
      adjunctive subconjunctival mitomycin-C (MMC). DESIGN: Case-controlled study.
      PARTICIPANTS: Of the 203 eyes of 203 primary open-angle glaucoma (POAG) patients
      who had undergone PGTP and in whom reliable Humphrey visual fields had been
      obtained both before and after surgery at 13.5 +/- 8.9 and 27.9 +/- 8.9 months,
      124 of the 144 eyes that received MMC during surgery were matched to the other 59
      eyes that did not with respect to cup-to-disc ratio and risk factors for
      filtration failure in addition to other variables. MAIN OUTCOME MEASURES: Both
      preoperative and postoperative intraocular pressure (IOP), Humphrey visual fields
      and their global indices, number of glaucoma medications, and best-corrected
      visual acuity (BCVA). RESULTS: There were no significant differences in
      demographics between the two groups (P > 0.05 for each). Whereas both the control
      and the MMC groups attained significant decreases of mean IOP (18.5 +/- 5.7 mmHg
      ;15.6 +/- 4.6 mmHg, P = 0.0014; 19.3 +/- 7.0 mmHg-13.7 +/- 4.9 mmHg, P = 0.0001)
      and mean number of medications (2.1 +/- 1.3-1.3 +/- 1.3, P = 0.0001; 2.3 +/- 1.2
      1.0 +/- 1.3, P = 0.0001) at 36 months after surgery, the MMC group had
      significantly lower mean IOP than the control group at all postoperative visits
      (P < 0.05 for each). The MMC group also tended to have less medical dependency
      after surgery than the control group. There was no significant difference in
      postoperative BCVA between the two groups. Patients in both groups had mean
      visual acuity of 20/30 or better. There was a significant worsening of corrected
      pattern standard deviation (CPSD) in the control group (3.97 +/- 3.18-5.17 +/-
      3.36, P = 0.001) compared with no significant change in the MMC group (5.07 +/-
      4.11-5.23 +/- 3.36, P = 0.93). The mean deviation did not change significantly in
      either group. CONCLUSIONS: The long-term glaucoma management in POAG patients
      with cataract undergoing PGTP indicates a successful outcome in final IOP,
      medical dependency, and BCVA. Furthermore, the MMC group had better IOP control
      and stable visual fields (CPSD), whereas the control group had a significant
      worsening of CPSD.

PMID- 12208707
TI  - The European glaucoma prevention study design and baseline description of the
      participants.
AB  - OBJECTIVES: The European Glaucoma Prevention Study seeks to evaluate the efficacy
      of reducing intraocular pressure (IOP), with dorzolamide to prevent or delay
      patients affected by ocular hypertension from developing primary open-angle
      glaucoma. DESIGN: Randomized, double-blinded, controlled clinical trial.
      PARTICIPANTS: Patients (age > or =30 years) were enrolled from 18 European
      centers. The patients fulfilled a series of inclusion criteria including the
      measurements of IOP (22-29 mmHg), two normal and reliable visual fields (VFs) (on
      the basis of mean defect and corrected pattern standard deviation/corrected loss
      of variance of standard 30/II Humphrey or Octopus perimetry), and normal optic
      disc as determined by the Optic Disc Reading Center (vertical and horizontal cup
      to-disc ratios; asymmetry between the two eyes < or =0.4). INTERVENTION: Patients
      were randomized to the treatment with dorzolamide or a placebo. MAIN OUTCOME
      MEASURES: End points are VF and/or optic disc changes. A VF change during the
      follow-up must be confirmed by two further positive tests. Optic disc change is
      defined by the agreement of two out of three independent observers evaluating
      optic disc stereo-slides. RESULTS: One thousand seventy-seven subjects were
      randomized between January 1, 1997 and May 31, 1999. The mean age was 57.03 +/-
      10.3 years; 54.41% were women and 99.9% were Caucasian. Mean IOP was 23.6 +/- 1.6
      mmHg in both eyes. Mean visual acuity was 0.97 +/- 0.11 in both eyes; mean
      refraction was 0.23 +/- 1.76 diopters in the right eye and 0.18 +/- 1.79 diopters
      in the left eye. Previous use of medication for ocular hypertension was reported
      by 38.4% of the patients, systemic hypertension by 28.1%, cardiovascular diseases
      by 12.9%, and diabetes mellitus by 4.7%. The qualifying VFs were normal and
      reliable according to protocol criteria. CONCLUSIONS: The mean IOP of the
      patients enrolled in the European Glaucoma Prevention Study is consistent with
      the estimated mean IOP (within the range of 22-29 mmHg) found in a large sample
      of the European population. The European Glaucoma Prevention Study should be able
      to better address the clinical question of whether pharmacological reduction of
      IOP (by means of dorzolamide) in ocular hypertension patients at moderate risk
      for developing primary open-angle glaucoma effectively lowers the incidence of
      primary open-angle glaucoma.

PMID- 12208708
TI  - A randomized paired eye comparison of two techniques for treating moderately high
      myopia: LASIK and artisan phakic lens.
AB  - OBJECTIVE: To compare refractive performance and safety of laser in situ
      keratomileusis (LASIK) and Artisan phakic intraocular lens (PIOL) for moderately
      high myopia. DESIGN: A prospective, randomized trial with paired eye control.
      PARTICIPANTS: Twenty-five patients with myopia ranging from -8.00 to -12.00
      diopters (D). INTERVENTION: For each patient, one eye received LASIK and the
      other one was implanted with an Artisan phakic intraocular lens. The treated eye
      and the surgical technique were randomized. MAIN OUTCOME MEASURES: Primary
      outcome measure was spherical equivalent refraction. Main secondary outcome
      measures were the change of two or more lines and safety index (ratio
      postoperative to preoperative best-corrected visual acuity). RESULTS: One year
      after surgery, the mean spherical equivalent refraction was -0.74 +/- 0.67 D for
      LASIK-treated eyes and -0.95 +/- 0.45 D for Artisan-treated eyes, and the
      majority of LASIK-treated eyes (64%) and Artisan-treated eyes (60%) were within
      +/-1.00 D of the intended result. At 1 month, the mean spherical equivalent
      refraction was -0.28 +/- 0.71 D for LASIK and -1.07 +/- 0.59 D for Artisan (P <
      0.01). The changes of two or more lines were in favor of Artisan (P < 0.05). The
      safety index was significantly better for Artisan (1.12 +/- 0.21) than for LASIK
      (0.99 +/- 0.17) at 1 year (P < 0.02). CONCLUSIONS: In cases of moderately high
      myopia, LASIK and Artisan phakic intraocular lenses seemed to produce a similar
      predictability. The best-corrected visual acuity and subjective evaluation of
      quality of vision were better for Artisan.

PMID- 12208709
TI  - Artisan phakic intraocular lens for myopia:short-term results of a prospective,
      multicenter study.
AB  - PURPOSE: To evaluate the safety and efficiency of the Artisan iris-supported
      phakic intraocular lens (Ophtec BV, Groningen, Netherlands) for the correction of
      high myopia. STUDY DESIGN: Nonrandomized, prospective, multicenter trial
      conducted under a United States Food and Drug Administration (FDA)
      Investigational Device Exemption. PARTICIPANTS: One hundred fifty-five eyes of
      155 patients with myopia from -5.5 to -22.5 diopters (D) underwent implantation
      of an Artisan lens, as part of a phase I, II, or III FDA trial. METHODS: Eyes
      were examined at 1 day (154 eyes), 2 weeks (142 eyes), 2 months (130 eyes), and 6
      months (84 eyes). Intraocular pressure and presence of flare and cell on slit
      lamp biomicroscopy were recorded at each visit. MAIN OUTCOME MEASURES: Achieved
      correction, stability of spherical equivalent refraction, change in astigmatism,
      postoperative uncorrected vision, change in best spectacle-corrected acuity, and
      change in endothelial cell count. RESULTS: Mean spherical equivalent manifest
      refraction stabilized on postoperative day 1. Mean difference between attempted
      and achieved correction at 2 months was -0.32 +/- 0.95 D (mean +/- standard
      deviation; range, -4.42 to +2.2 D). At 6 months, 85% of eyes saw 20/40 or better
      uncorrected, and 90% of eyes were within 1 D of the attempted correction.
      Refractive astigmatism increased in 4.8% of eyes and decreased in 17% of eyes at
      6 months. At 2 months, six eyes (4.8%) lost two or more lines of best spectacle
      corrected visual acuity; by 6 months, no eyes lost two or more lines of best
      corrected visual acuity. Endothelial cell count was unchanged at 6 months
      compared with the preoperative count. Nonprogressive lens opacities developed in
      four eyes as a result of surgical trauma. Chronic inflammation was not detected
      in any eye by slit-lamp biomicroscopy, nor did any eye develop angle closure or
      glaucoma. CONCLUSIONS: Short-term results suggest that the Artisan lens is an
      accurate and safe method for the correction of high myopia. Surgical skill is
      important in avoiding lens opacities. Longer-term data are needed to assess the
      impact of the lens on the endothelium, the crystalline lens, and the iris.

PMID- 12208710
TI  - Role of Orbscan II in screening keratoconus suspects before refractive corneal
      surgery.
AB  - OBJECTIVE: To evaluate the relationship between videokeratographic keratoconus
      screening programs and Orbscan II topography. DESIGN: Prospective, observational
      case series and instrument validation study. PARTICIPANTS: Sixty consecutive eyes
      with suspicious videokeratography (TMS-1, Tomey Technology, Waltham, MA) were
      evaluated before undergoing laser in situ keratomileusis (LASIK) surgery. A
      control group of 50 consecutive eyes without suspicious features by
      videokeratography was also evaluated. METHODS: Keratoconus screening programs,
      using the Rabinowitz and Klyce/Maeda methods and Orbscan II (Bausch & Lomb,
      Claremont, CA) topographies were performed on these patients. MAIN OUTCOME
      MEASURES: Specific parameters evaluated on the Orbscan II topographies were
      anterior elevation, posterior elevation, and thinnest pachymetry. RESULTS:
      Compared with a control group of patients without suspicious videokeratography,
      there was a statistically significant difference in the mean posterior elevation
      and mean anterior elevation in the groups with positive keratoconus testing with
      the Rabinowitz or Klyce/Maeda methods. For patients who met both the Rabinowitz
      and Klyce/Maeda criteria for keratoconus, the mean posterior elevation was 44 +/-
      2.5 micro m compared with a posterior elevation of 21 +/- 0.6 micro m for the
      control group. There was no statistically significant difference in the mean
      thinnest pachymetry between the control group and all keratoconus suspect groups.
      CONCLUSIONS: Patients with positive keratoconus screening tests have higher
      anterior and posterior elevation on Orbscan II topography. When used in
      combination with videokeratography, the Orbscan II topography system may be
      helpful in identifying patients who are potentially at high risk for developing
      ectasia after LASIK.

PMID- 12208711
TI  - LASIK correction of spherical hyperopia, hyperopic astigmatism, and mixed
      astigmatism with the LADARVision excimer laser system.
AB  - OBJECTIVE: To assess the safety and effectiveness of the LADARVision active
      tracking narrow beam excimer laser system (Alcon Surgical, Orlando, FL) using
      laser in situ keratomileusis (LASIK) for correction of spherical hyperopia,
      hyperopic astigmatism, and mixed astigmatism. DESIGN: A multicenter, prospective
      non-randomized (self-controlled) comparative trial. PARTICIPANTS: A total of 360
      eyes, including 152 spherical hyperopic, 143 hyperopic astigmatic, and 65 mixed
      astigmatic, were treated for up to +6.00-diopter (D) sphere with up to -6.00-D
      cylinder. INTERVENTION: Treatments were performed at six sites in the United
      States using a 6-mm optic zone with a 1.5-mm peripheral blend zone for a maximum
      ablation zone diameter of 9 mm. MAIN OUTCOME MEASURES: Uncorrected visual acuity
      (UCVA), manifest refraction, vector analysis, best spectacle-corrected visual
      acuity (BSCVA), complications and adverse reactions, subjective symptoms, and
      patient satisfaction. RESULTS: Six and 12 months of follow-up, respectively, were
      available on 143 and 117 spherical hyperopic eyes, 124 and 74 hyperopic
      astigmatic eyes, and 57 and 38 mixed astigmatic eyes, respectively. For spherical
      hyperopes at 6 and 12 months, UCVA was 20/40 or better in 93.4% and 93.9% of
      eyes, respectively. The manifest refraction spherical equivalent (MRSE) was
      within 0.50 D of intended in 65.0% and 74.1% of eyes, respectively, and within
      1.00 D in 87.4% and 91.4%, respectively. Refractive stability was demonstrated in
      94.2% or more of eyes between the intervals of 1 to 3 months and 3 to 6 months
      and in 95.3% or more of eyes to 12 months. A loss of two lines of BSCVA occurred
      in 3.5% and 3.4%, respectively, and no eyes lost more than two lines. For
      hyperopic astigmats at 6 and 12 months, UCVA was 20/40 or better in 90.9% and
      93.8% of eyes, respectively. The MRSE was within 0.50 D of intended in 60.5% and
      73.0% of eyes, respectively, and within 1.00 D in 88.7% and 89.2% of eyes,
      respectively. Refractive stability was demonstrated in 96.5% or more of eyes,
      respectively, between the intervals of 1 to 3 months and 3 to 6 months and 95.5%
      or more to 12 months. A loss of two lines of BSCVA occurred in 5.8% and 1.4% of
      eyes, respectively, and no eyes lost more than two lines. For mixed astigmats at
      6 and 12 months, UCVA was 20/40 or better in 92.6% and 94.4% of eyes,
      respectively. The MRSE was within 0.50 D of intended in 64.9% and 73.7% of eyes,
      respectively, and within 1.00 D in 87.7% and 94.7% of eyes, respectively.
      Refractive stability was demonstrated in 100% of eyes between the intervals of 1
      to 3 months and 3 to 6 months and in 97.0% or more to 12 months. A loss of two
      lines of BSCVA occurred in 1.9% and 0.0% of eyes, respectively, and no eyes lost
      more than two lines. CONCLUSIONS: The data support safety and effectiveness of
      the LASIK correction of spherical hyperopia, hyperopic astigmatism, and mixed
      astigmatism with the LADARVision system.

PMID- 12208713
TI  - Intraocular pressure after LASIK for hyperopia.
AB  - PURPOSE: To determine whether hyperopic laser in situ keratomileusis (H-LASIK)
      affects Goldmann applanation tonometry measurements. DESIGN: Retrospective,
      comparative, self-controlled case series. PARTICIPANTS: One hundred eight eyes of
      58 patients were enrolled in the study. METHODS: Baseline intraocular pressure
      (IOP) was measured by Goldmann applanation tonometry. These readings were
      compared with readings obtained at least 6 months after surgery. RESULTS: After H
      LASIK, a decrease was observed in the measured IOP of treated eyes that could not
      be related to the degree of hyperopia treated or to the treatment zone diameter.
      A significant difference was observed between the IOP before and after surgery (P
      < 0.00001). CONCLUSIONS: The applanation tonometer underestimates the true IOP
      after LASIK for hyperopia.

PMID- 12208714
TI  - Acquired cataracts after diode laser photocoagulation for threshold retinopathy
      of prematurity.
AB  - PURPOSE: To report the incidence of acquired cataract after diode laser
      photocoagulation for threshold retinopathy of prematurity at our institution.
      DESIGN: Retrospective, noncomparative, interventional case series. PARTICIPANTS:
      One hundred fifty-three infants (293 eyes) with threshold retinopathy of
      prematurity. INTERVENTION: Transpupillary diode laser photocoagulation. MAIN
      OUTCOME MEASURE: Acquired cataract formation. RESULTS: One cataract (0.003%) in
      293 eyes occurred after transpupillary diode laser photocoagulation. This
      cataract consisted of peripheral cortical punctate lenticular opacities that were
      not progressive or visually significant. CONCLUSIONS: The risk of acquired
      cataract after transpupillary diode laser photocoagulation for threshold
      retinopathy of prematurity is low. Transpupillary diode laser photocoagulation
      may be safer than argon laser photocoagulation for treatment of threshold
      retinopathy of prematurity.

PMID- 12208715
TI  - Snowflake degeneration of polymethyl methacrylate posterior chamber intraocular
      lens optic material: a newly described clinical condition caused by unexpected
      late opacification of polymethyl methacrylate.
AB  - OBJECTIVE: To report 25 cases of gradual, but sometimes progressive, late
      postoperative degeneration of polymethyl methacrylate (PMMA) optics of posterior
      chamber (PC) intraocular lens (IOL) implants, often resulting in a clinically
      significant visual decrease long after the implantation, sometimes to a severity
      that required IOL explantation/exchange. DESIGN: Analysis of explanted PC IOLs,
      clinical histories, and photographs. PARTICIPANTS: We analyzed 25 case
      histories/photographs and/or explants from 18 patients implanted in the 1980s to
      mid-1990s with three-piece PC IOLs with PMMA optics and with polypropylene or
      PMMA haptics. The IOL optic from each case had characteristic snowflake or
      crystalline opacifications. This condition occurred with more than one
      manufacturer and in some cases was restricted to certain lot numbers. METHODS:
      The explanted IOLs (n = 10) were studied by gross inspection and by light and
      scanning electron microscopy, as well as confocal and energy dispersive
      spectroscopy. MAIN OUTCOME MEASURES: The snowflake lesions were noted within the
      IOL optics. The nature of these lesions was investigated. RESULTS: Assimilation
      of clinical information with pathologic and morphologic profiles of all cases
      suggested that the snowflake opacification was a small spherical lesion
      surrounded by an outer pseudocapsule composed of compressed, degenerated PMMA,
      with a central core containing convoluted fragments of PMMA. The lesions were
      classified into four clinical and pathologic grades according to their density
      and severity. CONCLUSIONS: This is the first clinicopathologic correlative report
      on this complication. We postulate that manufacturing variations in some IOL
      models fabricated in the 1980s and early 1990s are responsible. The snowflake
      lesions seem to represent a destruction of the PMMA material. The cluster of
      lesions in implanted lenses manufactured by Surgidev was less progressive than
      some other models, including lenses made by IOPTEX Research Corporation. This
      identification of a condition previously unreported is important to alert
      clinicians regarding these perplexing lesions that may otherwise be considered
      idiopathic, with no obvious clinical hint as to their origin. The prevalence
      noted thus far is still too low to in any way suggest that this condition would
      occur in 100% of PMMA IOLs from these manufacturers. However, these late
      occurring lesions, present in lens models that were implanted in hundreds of
      thousands of patients in the last decade or so, could have constituted a true
      epidemic, except that many of the patients are now deceased.

PMID- 12208716
TI  - Prognosis of ischemic internuclear ophthalmoplegia.
AB  - OBJECTIVES: To determine the prognosis of internuclear ophthalmoplegia (INO)
      caused by infarction. DESIGN: Multicenter, retrospective observational case
      series. PARTICIPANTS: Thirty three patients with ischemic-related INO. METHODS:
      Chart review of clinical details. MAIN OUTCOME MEASURE: Resolution of diplopia in
      primary position. RESULTS: Of the group, 78.8% demonstrated resolution of
      diplopia in primary position with an average time to resolution of 2.25 months.
      The presence of associated neurologic symptoms (vertigo, ataxia, dysarthria,
      facial palsy, pyramidal tract signs) correlated with a worse prognosis for
      resolution of diplopia. When performed magnetic resonance imaging (MRI)
      demonstrated the causative infarct in only 52% of cases; the presence of an MRI
      demonstrable lesion was not significantly associated with prognosis for
      resolution. CONCLUSIONS: Similar to ischemic ocular motor palsies, most ischemic
      based INO become asymptomatic in primary position over 2 to 3 months. The
      presence of associated features correlated with persistent diplopia. MRI has
      limited yield in demonstrating the causative infarct.

PMID- 12208718
TI  - Cavernous sinus dural arteriovenous malformations: patterns of venous drainage
      are related to clinical signs and symptoms.
AB  - OBJECTIVE: To provide evidence that venous congestion and drainage patterns are
      responsible for the manifestations of cavernous sinus area dural arteriovenous
      malformations (CSdAVMs). DESIGN: Retrospective observational case series.
      PARTICIPANTS: Records of 85 patients with complete clinical and angiographic
      evaluations of CSdAVMs were evaluated for the clinical features of the disorder.
      A neuroradiologist analyzed patterns of venous drainage to and from the cavernous
      sinus without knowledge of the clinical features. Four venous drainage patterns
      (reversal of flow from the CSdAVMs into the anterior cavernous sinus, ophthalmic
      vein thrombosis, drainage into the inferior petrosal sinus or drainage into the
      superior petrosal sinus) were statistically tested for their predictive value of
      signs and symptoms using logistic regression. MAIN OUTCOME MEASURES: The power of
      prediction of orbital congestion, elevated IOP, extraocular muscle dysfunction,
      optic neuropathy, venous-stasis retinopathy, choroidal effusion, anterior chamber
      shallowing, bruits, cranial nerve paresis, and central nervous system dysfunction
      from four patterns of venous drainage. RESULTS: Reversal of drainage into the
      anterior cavernous sinus and ophthalmic veins was highly predictive (P = 0) of
      orbital congestion, which was seen in 77 (91%) patients. In contrast, eight (9%)
      patients without orbital congestion had shunts that did not drain into the
      anterior cavernous sinus and ophthalmic veins. Cavernous sinus dural
      arteriovenous malformation drainage into the anterior cavernous sinus and
      ophthalmic veins also predicted elevated IOP (P = 0.0023) and optic neuropathy (P
      = 0.047). Ophthalmic vein thrombosis significantly predicted cases with choroidal
      effusion (P = 0.002) and anterior chamber shallowing (P = 0.01). Third nerve
      paresis could be predicted from flow toward the inferior petrosal sinuses (P =
      0.017). Central nervous system symptoms or dysfunction, occurring in 7 (8%)
      patients, was predicted by venous drainage into the superior petrosal sinus (P =
      0.0008). CONCLUSIONS: The clinical features found in patients with CSdVAMs are
      related to the abnormal venous drainage and can be predicted by these venous
      drainage patterns. Venous congestion and hypertension seem to cause the clinical
      dysfunction in this disorder.

PMID- 12208717
TI  - Use of magnetic resonance imaging to differentiate optic neuritis and
      nonarteritic anterior ischemic optic neuropathy.
AB  - OBJECTIVE: To determine if magnetic resonance imaging (MRI) of the optic nerves
      obtained during the acute phase can distinguish patients with optic neuritis (ON)
      from those with nonarteritic anterior ischemic optic neuropathy (NAION). DESIGN:
      Retrospective, neuroradiologic, observational study. PARTICIPANTS: Sixty-four
      patients diagnosed as having either ON or NAION who were diagnosed by clinical
      criteria and imaged by MRI. METHODS: Demographic information on the MRI scans was
      masked and the patients were presented randomly and in a blinded fashion to a
      neuroradiologist (JDR) for determination of abnormalities. Reproducibility was
      assessed by presenting 10 of the scans a second time to the same
      neuroradiologist. MAIN OUTCOME MEASURES: The presence or absence and location of
      abnormal MRI signals of the optic nerve. RESULTS: Evaluation of reproducibility
      revealed identical interpretations of the ten scans submitted a second time. The
      optic nerve was abnormal in the clinically affected eye in 31 of the 32 ON
      patients but in only 5 of the 32 NAION patients. Thirty of the 31 ON patients who
      received gadolinium had enhancement, and 27 of the 32 ON patients had increased
      short T(1) inversion recovery signal in the clinically affected optic nerve. The
      five NAION patients with abnormal scans in the clinically affected eye had
      increased short T(1) inversion recovery signal, and in two of these, there also
      was enhancement of the optic nerve. For the ON patients, enhancement involved the
      entire length of the intraorbital optic nerve in 18 cases and the intracranial
      segment of the optic nerve in 19 cases. CONCLUSIONS: Our study shows that MRI
      scanning of the optic nerve shows significantly different results between
      patients clinically diagnosed with either ON or NAION.

PMID- 12208719
TI  - Loss of stereopsis with optic chiasmal lesions and stereoscopic tests as a
      differential test.
AB  - OBJECTIVE: To identify and characterize the loss of stereopsis observed in
      patients with lesions of the optic chiasm. STUDY DESIGN: Cross-sectional study.
      PARTICIPANTS: Forty-three patients who had good visual acuity with orthophoria
      and without strabismologic histories were divided into two groups. Group 1
      consisted of 13 patients with lesions involving the optic chiasm (regardless of
      their visual field loss) diagnosed by magnetic resonance imaging findings. Group
      2 (control group) consisted of 30 patients who had large absolute visual field
      defects as a result of other causes, including 11 intracranial disorders other
      than optic chiasmal lesions, 11 cases of open-angle glaucoma, and 8 patients with
      lesions of the retina. METHODS: The stereoacuity and visual field in each case in
      group 1 (before and after surgery) and group 2 were assessed, and the results
      were compared. MAIN OUTCOME MEASURES: Stereoacuity was assessed by the Titmus
      stereo test (normal value for circle, 6/9; 80 seconds of arc) and by Lang
      stereotest (normal value for circle, 3/3; 350 seconds of arc). Visual field was
      evaluated by Goldmann and Humphrey perimetry (conventional perimetry), the
      starlight test (binocular visual field test), and scanning laser ophthalmoscopic
      microperimetry (microperimetry). RESULTS: Before surgery, 11 of 13 cases (85%) in
      group 1 failed stereo tests, and after surgery, 5 of 13 cases (38%) in group 1
      failed stereo tests. Before surgery, four patients who failed stereo tests showed
      no absolute scotoma by Humphrey or Goldmann analysis; after surgery, one patient
      who failed stereo tests showed no absolute scotoma by Humphrey or Goldmann
      analysis. However, starlight testing showed complete bitemporal hemianopsia only
      under binocular conditions, and microperimetry demonstrated a relative bitemporal
      hemianopsia at the fixating point. No patient failed in the Titmus circle test,
      but one patient in group 2 failed the Lang test (3%). The patients with chiasmal
      lesions significantly lost the ability of stereopsis compared with other diseases
      (group 1 [before or after surgery] vs. group 2, P < 0.001, Fisher's exact test).
      Conventional perimetry was unable to measure scotomas within 3 degrees of the
      fixation point, which is the key area for acute foveal stereopsis, because of an
      attached observational mirror. CONCLUSIONS: The difficulty with stereopsis in
      patients with lesions of the optic chiasm is most likely caused by the
      compression of the decussating optic nerve fibers resulting in the loss of an
      overlapping visual field at the fixation point. Stereo tests were demonstrated to
      be simple and effective adjunctive tests for suspected chiasmal compression.

PMID- 12208720
TI  - Classification and prediction of the progression of thyroid-associated
      ophthalmopathy by an artificial neural network.
AB  - OBJECTIVE: We have used an artificial neural network in an attempt to classify
      and predict the progression of thyroid-associated ophthalmopathy (TAO) at the
      first clinical examination. DESIGN: This retrospective comparative case series
      included a group of patients examined by the ophthalmologist only once because of
      the absence of signs of progressive disease (GR1), as subsequently monitored by
      an endocrinologist, and a group of patients on follow-up because of progressive
      disease (GR2). PARTICIPANTS AND METHODS: We examined 242 patients, of whom 207
      were women and 35 were men. GR1 included 129 patients (257 eyes) who, on
      ophthalmologic assessment, were further classified as having no TAO (n = 53;
      GR1a) and only lid signs or inactive, stable TAO (n = 76; GR1b). GR2 included 113
      patients (219 eyes). One hundred three normal subjects (205 eyes), 50 women and
      53 men, were tested to provide normal ranges for proptosis values. We applied a
      model of back propagation neural network with 17 input variables, a training
      matrix of 414 observations, a randomly selected test group of 115 observations,
      and, as output, the progression of disease. The ophthalmologic assessment
      included (1) lid fissure measurement, (2) Hertel, (3) color vision, (4) cover
      test and Hess screen, (5) visual acuity, (6) tonometry, (7) fundus examination,
      (8) visual field, and (9) orbital computed tomography scan or ultrasonography.
      Other parameters included in the neural analysis were gender and age of the
      patients, their cigarette smoking, and the interval between follow-up visits.
      RESULTS: The prevalence of smokers among patients without TAO was significantly
      lower than that among those with TAO (P < 0.03). Mean proptosis values (Hertel)
      were significantly different in GR1, in GR2, and in a group of normal eyes (P <
      0.0001), and the changes of values in consecutive measurements were associated
      with progression of the disease (P < 0.01). Differences of the proptosis values
      in the two groups of patients were not related to smoking. The neural network
      correctly classified 78.3% of 115 eyes (87 patients) and predicted TAO
      progression in 69.2% of 39 eyes (28 patients). CONCLUSIONS: In our opinion,
      neural network analysis can be successfully applied for classifying TAO and
      predicting progression at the first clinical examination.

PMID- 12208721
TI  - Role of intravitreal methotrexate in the management of primary central nervous
      system lymphoma with ocular involvement.
AB  - PURPOSE: To evaluate the safety and efficacy of intravitreal methotrexate in the
      management of primary central nervous system lymphoma (PCNSL) involving the eye.
      DESIGN: Retrospective noncomparative interventional case series. PARTICIPANTS:
      Sixteen human immunodeficiency virus-negative white patients (5 males and 11
      females, aged 30-76 years) with intraocular B cell lymphoma treated with
      intravitreal methotrexate at Oregon Health & Science University or Hadassah
      University Hospital between August 1995 and September 2000. INTERVENTION:
      Patients were treated with intravitreal methotrexate (400 micro g/0.1 ml)
      according to a standard induction-consolidation-maintenance regimen and monitored
      by serial examinations, including measurement of visual acuity, slit-lamp
      biomicroscopy, and dilated funduscopy. MAIN OUTCOME MEASURES: Clinical response
      to intravitreal chemotherapy, number of injections for clinical remission, visual
      acuity, complications during study period, length of survival from diagnosis, and
      cause of death. RESULTS: Time of follow-up from commencement of the methotrexate
      injections was 6 to 35 months (median, 18.5 months). Twenty-six of 26 eyes (100%)
      were cleared clinically of malignant cells after a maximum of 12 methotrexate
      injections. A second remission was induced in three patients, who were treated
      with a further course of intravitreal chemotherapy after their tumor recurred
      within the eye. Complications that occurred during the period of treatment and
      follow-up included cataract (73% of 26 eyes), corneal epitheliopathy (58% of 26
      eyes), maculopathy (42% of 26 eyes), vitreous hemorrhage (8% of 26 eyes), optic
      atrophy (4% of 26 eyes), and sterile endophthalmitis (4% of 26 eyes). No patient
      had irreversible loss of vision that could be definitely attributed to the
      intravitreal injection of methotrexate. CONCLUSIONS: Intravitreal chemotherapy
      with methotrexate is effective in inducing clinical remission of intraocular
      tumor in PCNSL with acceptable morbidity. Further study is indicated to determine
      whether this approach extends life expectancy.

PMID- 12208722
TI  - Human T-cell lymphotropic virus type-1 associated t-cell leukemia/lymphoma
      masquerading as necrotizing retinal vasculitis.
AB  - OBJECTIVE: To report a case of adult T-cell leukemia/lymphoma (ATL) presenting as
      a bilateral retinal vasculitis and diagnosed by molecular detection of a
      rearrangement in the T-cell receptor (TCR) and the presence of the human T-cell
      lymphotropic virus type 1 (HTLV-1) pol gene in the malignant lymphoid cells.
      DESIGN: Case report. METHODS: Routine histologic and immunohistochemical analyses
      were performed on the retinal biopsy specimen before referral to the National Eye
      Institute. Lymphoid cells associated with granulomatous inflammation infiltrating
      the retina and surrounding retinal blood vessels were microdissected from the
      paraffin sections of the retinal biopsy specimen. The polymerase chain reaction
      (PCR) was performed using primers for the TCR gene and HTLV-1 pol and gag genes.
      RESULTS: Microscopic examination showed a necrotizing granulomatous retinal
      vasculitis with a predominant T-cell infiltrate detected by immunohistochemistry.
      Molecular analysis demonstrated a clonal rearrangement of the TCR and the
      presence of the HTLV-1 pol gene in the microdissected lymphoid cells diagnostic
      of ATL. CONCLUSIONS: Necrotizing retinitis and retinal vasculitis are rare
      manifestations of ATL. Human T-cell lymphotropic virus type 1 infection should be
      considered in the differential diagnosis of patients from endemic areas who have
      retinal vasculitis at presentation. This case further demonstrates the usefulness
      of microdissection and PCR for the diagnosis of ocular disease, including HTLV-1
      infection.

PMID- 12208723
TI  - Acetazolamide for central serous retinopathy.
AB  - OBJECTIVE: To find out whether acetazolamide has a beneficial effect in the
      treatment of central serous retinopathy (CSR). DESIGN: Prospective,
      nonrandomized, comparative trial. PARTICIPANTS: Fifteen acetazolamide-treated and
      7 untreated (control) CSR patients who completed at least 24 months of follow-up.
      METHODS: Patients in the treatment group were given systemic acetazolamide
      according to a standard protocol. Main outcome measures were compared between
      treatment and control groups using Student's t test and the Mann-Whitney U test
      for statistical analysis. MAIN OUTCOME MEASURES: Time until subjective visual
      improvement, time until full clinical resolution, and rate of recurrences.
      RESULTS: Mean times to both subjective visual improvement and clinical resolution
      of the attack were shorter in the study group than in the control group.
      Recurrence rate did not differ between the study and control groups. CONCLUSIONS:
      Acetazolamide treatment for CSR shortens the time for subjective and objective
      clinical resolution, but has no effect on either final visual acuity or
      recurrence rate of the disease.

PMID- 12208724
TI  - Angiographic and flow patterns of retinal choroidal anastomoses in age-related
      macular degeneration with occult choroidal neovascularization.
AB  - OBJECTIVE: To identify the angiographic features of retinal choroidal anastomoses
      (RCAs) in patients with newly diagnosed occult choroidal neovascularization (CNV)
      in the setting of age-related macular degeneration (AMD) and to determine the
      sequence of flow between the RCA and the CNV. DESIGN: Retrospective cross
      sectional study. PARTICIPANTS: The angiograms of 205 eyes of 153 consecutive
      patients with occult CNV on fluorescein angiography (FA) and focal hot spots on
      indocyanine green angiography (ICGA) were evaluated retrospectively. METHODS OF
      TESTING: Red-free photographs and sequential digital fluorescein and indocyanine
      green angiograms obtained by confocal scanning laser ophthalmoscope (the
      Heidelberg Retina Angiograph; Heidelberg Engineering GmbH, Dossenheim, Germany).
      MAIN OUTCOME MEASURES: The angiograms were evaluated for the presence of RCA. The
      following angiographic characteristics were recorded: number and type of
      anastomoses, location, distance from fovea, area of CNV, presence of pigment
      epithelium detachment (PED), cystoid macular edema on FA, and intraretinal
      leakage on ICGA. The direction of flow between the RCA and the CNV was identified
      by analyzing high-speed angiograms. RESULTS: Retinal choroidal anastomoses were
      identified in 57 eyes (28%), in 49 of 154 eyes with PED (32%), and in 8 of 51
      eyes without PED (16%). Of 109 anastomoses, 70% were venous and 30% were
      arterial. Ninety-six percent of the eyes had at least one venous anastomosis, 49%
      of the eyes had an arterial anastomosis, and 46% of the eyes had both. Cystoid
      macular edema was seen on FA in 37 eyes (65%), and intraretinal indocyanine green
      leakage was noted in 52 eyes (91%). Twenty-two eyes that underwent high-speed
      ICGA were analyzed for the direction of flow. All 15 eyes having arterial and
      venous anastomoses demonstrated a filling pattern from the retinal arteriole to
      the CNV, followed by the retinal venule. Seven eyes with venous RCA showed flow
      sequence from the CNV to the collecting retinal venule. CONCLUSIONS: Our study
      supports the presence of RCA in the early stages of acute exudative AMD with
      occult CNV, mainly with serous PED. High-speed angiography helps to identify the
      filling sequence of the RCA and the CNV, and therefore may guide the clinician in
      planning treatment strategies.

PMID- 12208725
TI  - Patient selection for macular translocation surgery using the scanning laser
      ophthalmoscope.
AB  - OBJECTIVES: To evaluate the use of the scanning laser ophthalmoscope (SLO) as a
      predictor for potential visual improvement in eyes with subfoveal choroidal
      neovascularization (CNV) secondary to age-related macular degeneration (AMD)
      undergoing limited macular translocation. DESIGN: Retrospective noncomparative
      case series. PARTICIPANTS: Consecutive series of 71 eyes of 70 patients with
      subfoveal CNV secondary to AMD that underwent effective and uncomplicated limited
      macular translocation at the Wilmer Ophthalmological Institute. METHODS:
      Evaluation of the fundus microperimetry and fixation pattern was conducted on all
      patients using the Rodenstock scanning laser ophthalmoscope (G. Rodenstock
      Instrument GmbH, Munich, Germany) within 72 hours before surgery. MAIN OUTCOME
      MEASURES: Sensitivity and specificity in addition to positive and negative
      predictive values of SLO findings for visual outcome after macular translocation.
      RESULTS: Stable fixation presented the highest positive predictive value for
      visual acuity equal to or better than 20/100 (30 of 33 = 0.91), and predominantly
      eccentric fixation had the highest negative predictive value for visual acuity
      worse than 20/100 (7 of 9 = 0.78). Sensitivity was higher for the presence of
      predominantly central fixation (42 of 48 = 0.87), and specificity was higher for
      relatively unstable/unstable fixation (20 of 23 = 0.87). CONCLUSIONS: Eyes with
      stable and central fixation (without dense central scotoma) good preoperative
      visual acuity, and short length of symptoms are those with the greatest chance to
      achieve good vision after macular translocation. The knowledge of the fixation
      and microperimetry pattern enables better understanding of the macular function
      in eyes with AMD and may be useful for evaluation of baseline retinal cell
      viability. Incorporation of these testing modalities may help to optimize patient
      selection for macular translocation or other future techniques aimed at rescuing
      photoreceptors.

PMID- 12208726
TI  - Rapid and durable recovery of visual function in a patient with von hippel-lindau
      syndrome after systemic therapy with vascular endothelial growth factor receptor
      inhibitor su5416.
AB  - PURPOSE: To present a case of rapid and durable recovery of visual function in a
      patient with von Hippel-Lindau syndrome and optic nerve head hemangioblastoma
      after systemic treatment with the vascular endothelial growth factor (VEGF)
      receptor inhibitor SU5416. DESIGN: Interventional case report. METHODS: Visual
      function parameters, including visual acuity, automated visual field, and
      contrast sensitivity, were evaluated using standardized methods repeatedly over a
      15-month period. Fundus photographs and fluorescein angiograms were also
      obtained. Central nervous system lesions were monitored by computed tomography
      (CT) and magnetic resonance imaging (MRI) scans. Treatment involved the systemic
      administration of the VEGF receptor inhibitor SU5416. MAIN OUTCOME MEASURES:
      Clinical presentation, visual acuity using Early Treatment Diabetic Retinopathy
      Study protocol, Humphrey automated perimetry, (Zeiss Humphrey Systems, Dublin,
      CA) Vistech contrast sensitivity (Vistech Consultants Inc., Dayton, OH)
      Farnsworth (Farnsworth-Munsell Color Services, New Windsor, NY) dichotomous panel
      D-15, retinal photography, fluorescein angiography, and CT and MRI scans.
      RESULTS: Within 4 weeks of therapy, visual acuity had improved from 20/32(-2) to
      20/16(-1), the visual field had expanded from being circumferentially constricted
      to within 8 degrees of fixation to normal, and contrast sensitivity improved in
      all but the lowest spatial frequency (1.5 cycles/degree). No change was observed
      in lesion size by fundus photography. Improvement has been maintained over 18
      months with intermittent SU5416 therapy. CONCLUSIONS: We report rapid, extensive,
      and durable recovery of visual function after systemic administration of the VEGF
      receptor inhibitor SU5416 to a patient with VHL syndrome and optic nerve head
      hemangioblastoma. These findings suggest that continued evaluation of VEGF
      inhibitors for ocular neovascular disorders is warranted.

PMID- 12208727
TI  - Limbal versus conjunctival autograft transplantation for advanced and recurrent
      pterygium.
AB  - PURPOSE: To compare the safety and efficacy of limbal versus conjunctival
      autograft transplantation for treating advanced and recurrent pterygia. DESIGN:
      Randomized, prospective clinical trial. PARTICIPANTS: Seventy-nine patients with
      advanced primary or recurrent pterygia treated by conjunctival (n = 36) or limbal
      conjunctival (n = 43) autograft transplantation. INTERVENTION: Twenty four eyes
      with primary and 12 eyes with recurrent pterygia underwent free conjunctival
      autograft transplantation (group A), and 28 eyes with primary and 15 eyes with
      recurrent pterygia underwent limbal-conjunctival autograft transplantation (group
      B). MAIN OUTCOME MEASURES: Recurrence of pterygium and complications. RESULTS:
      With a 3-year minimum of follow-up, 2 cases of primary (8.3%) and 4 cases of
      recurrent (33.3%) pterygia in group A showed recurrence. No patients in group B
      developed recurrence. CONCLUSIONS: In this study both techniques were effective
      in cases of advanced primary pterygia with no statistically significant
      difference. Limbal transplantation appeared more effective than free conjunctival
      transplantation for treatment of recurrent pterygia (P < 0.05).

PMID- 12208728
TI  - HERG K+ channel, a regulator of tumor cell apoptosis and proliferation.
AB  - The human ether-a-go-go related gene (HERG) encodes K+ channel identified as a
      molecular target for mutations underlying some forms of the long Q-T syndrome, a
      lethal cardiac arrhythmia. Recent studies revealed that HERG is abundantly
      expressed in a variety of tumor cells. Yet, the role of HERG in tumor cells had
      remained unclear. Here, we show that HERG conductance markedly promotes H2O2
      induced apoptosis of various tumor cells, whereas HERG expression facilitates the
      tumor cell proliferation caused by tumor necrosis factor (TNF) ligand (TNF
      alpha). Immunostaining and immunocoprecipitation reveal coexpression of HERG and
      TNF receptor 1 on the cytoplasmic membrane, which is correlated with greater
      activities of nuclear transcription factor, nuclear factor-kappaB, in HERG
      expressing tumor cells. Our data suggest that HERG K+ channel is a regulator of
      tumor cell proliferation and apoptosis and provide a potential new target for
      cancer therapy.

PMID- 12208729
TI  - Expression of estrogen receptor (ER) (beta)cx protein in ER(alpha)-positive
      breast cancer: specific correlation with progesterone receptor.
AB  - Estrogen receptor (ER) (beta)cx, a splice variant of ERbeta, is a dominant
      repressor of ER(alpha) function. In this study we investigated the possibility
      that because the progesterone receptor (PR) gene is a downstream target of
      activated ER(alpha), in ER(alpha)-positive breast cancers, expression of
      ER(beta)cx would result in repression of PR. In ER(alpha)-positive MCF-7 cells,
      stable transfection of an ER(beta)cx expression vector resulted in reduced
      expression of PR without affecting ER(alpha) expression. In breast cancers,
      immunohistochemical evaluation of ER(alpha)-positive foci for the expression of
      PR and ER(beta)cx revealed a significant correlation between a PR-negative
      phenotype and the presence of ER(beta)cx within the foci. However, when entire
      lesions were evaluated by Allred scoring in 115 ER(alpha)-positive breast cancer
      specimens, the presence of two distinct groups of patients could be discerned.
      One group expressed ER(beta)cx and had very reduced levels of PR expression, as
      expected. The second group showed both ER(beta)cx and high levels of PR. To
      evaluate the role of ER(beta)cx in sensitivity to tamoxifen, 18 core needle
      biopsies, obtained before preoperative treatment with tamoxifen, were
      investigated. The results show that expression of ER(beta)cx in primary lesions
      correlated with a poor response to tamoxifen, especially in cancers with a low PR
      expression in Allred score. This is the first evidence that evaluation of
      ER(beta)cx along with PR may contribute to a better characterization of ER(alpha)
      positive breast cancers.

PMID- 12208730
TI  - Copper deficiency induced by tetrathiomolybdate suppresses tumor growth and
      angiogenesis.
AB  - Copper plays an essential role in promoting angiogenesis. Tumors that become
      angiogenic acquire the ability to enter a phase of rapid growth and exhibit
      increased metastatic potential, the major cause of morbidity in cancer patients.
      We report that copper deficiency induced by tetrathiomolybdate (TM) significantly
      impairs tumor growth and angiogenesis in two animal models of breast cancer: an
      inflammatory breast cancer xenograft in nude mice and Her2/neu cancer-prone
      transgenic mice. In vitro, TM decreases the production of five proangiogenic
      mediators: (a) vascular endothelial growth factor; (b) fibroblast growth factor
      2/basic fibroblast growth factor; (c) interleukin (IL)-1alpha; (d) IL-6; and (e)
      IL-8. In addition, TM inhibits vessel network formation and suppresses nuclear
      factor (NF)kappaB levels and transcriptional activity. Our study suggests that a
      major mechanism of the antiangiogenic effect of copper deficiency induced by TM
      is suppression of NFkappaB, contributing to a global inhibition of NFkappaB
      mediated transcription of proangiogenic factors.

PMID- 12208731
TI  - Expression of cIAP1, a target for 11q22 amplification, correlates with resistance
      of cervical cancers to radiotherapy.
AB  - Inhibition of, or increased resistance to, apoptosis is a common property of
      cancer cells. This means that a constitutive activation of antiapoptotic
      molecules via genetic or epigenetic mechanisms, including gene amplification, may
      well be involved in carcinogenesis. Recently we reported that cIAP1, an inhibitor
      of apoptosis, is overexpressed through 11q22 amplification in cell lines derived
      from esophageal squamous cell carcinomas and is associated with resistance of
      esophageal squamous cell carcinomas to drug-induced apoptosis (I. Imoto et al.
      Cancer Res., 61: 6629-6634, 2001). Because amplification of 11q22 has been
      implicated in other malignancies also, including cervical squamous cell
      carcinomas (CSCCs), we attempted to correlate amplification and overexpression of
      cIAP1 with radiation sensitivity in CSCC-derived cell lines and primary CSCC
      tumors. In the nine cell lines we examined, two showed amplification and
      consistent overexpression of cIAP1, as well as significant resistance to
      radiation-induced cell death as compared with lines showing no cIAP1
      amplification. Immunohistochemical analysis of 70 primary CSCCs from patients
      treated only with radiotherapy demonstrated that both overall survival and local
      recurrence-free survival was significantly poorer among patients with tumors
      showing high levels of nuclear cIAP1 staining than among patients whose tumors
      revealed little or no nuclear cIAP1. Multivariate analysis showed nuclear cIAP1
      staining to be an independent predictive factor for local recurrence-free
      survival after radiotherapy among patients with CSCC. These findings demonstrate
      that cIAP1 may play an important role in the development/progression of this
      disease and that cIAP1 could be a novel predictive marker for resistance to
      radiotherapy in individual CSCC patients.

PMID- 12208732
TI  - TrkA as a life and death receptor: receptor dose as a mediator of function.
AB  - Nerve growth factor (NGF) has been implicated as both an inhibitor and an inducer
      of apoptosis. Binding of NGF to its TrkA receptor is generally considered to have
      an antiapoptotic effect. However, neuroblastomas that overexpress TrkA have a
      good prognosis and frequently regress by apoptosis either spontaneously or after
      chemotherapeutic treatment, whereas those that express little or no TrkA are
      lethal in 80-95% of patients, despite maximal therapy. We now report that NGF
      treatment of PC12 neural crest tumor cells trkA-transfected to express TrkA at
      levels analogous to those seen in "good prognosis" neuroblastomas results in cell
      death; similar treatment of native cells that express TrkA at levels similar to
      those of "poor prognosis" neuroblastomas has no effect on cell survival.
      Morphological and biochemical studies indicate that NGF induces atypical
      apoptosis that is abrogated by the tyrosine kinase inhibitor K252alpha, but not
      by an inhibitor of NGF-p75 binding, in trkA-transfected PC12 cells. Differential
      activation of the TrkA-phosphorylated mitogen-activated protein
      (MAP)/extracellular signal-regulated kinase (ERK) kinase 1-phosphorylated ERK
      phosphorylated cAMP-responsive element-binding protein and TrkA-phosphorylated
      MAP/ERK kinase 3/6-phosphorylated p38 MAP signal transduction pathways, also
      suppressible by K252alpha, occurs in the two cell types. This difference may
      mediate their differential survival after exposure to NGF.

PMID- 12208733
TI  - Demonstration of Epstein-Barr virus in carcinomas of various sites.
AB  - EBV is an etiological agent in infectious mononucleosis, is implicated in some
      malignant lymphomas and lymphoepithelioma-like carcinomas, and has been
      sporadically reported in carcinomas of the breast, lung, and other sites. We
      studied immunohistochemically benign and malignant tumors of the breast, lung,
      colon, and prostate and found EBV in some carcinomas of those sites. Also, EBV
      reactions were noted in hyperplasias and dysplasias, e.g., breast carcinomas in
      situ and prostatic intraepithelial neoplasia. Benign tumor counterparts were
      negative. PCR analysis of selected cases confirmed the presence of EBV. Our
      results suggest that EBV is not restricted to lymphoepithelioma-like carcinomas
      but may play an oncogenic role in frequent epithelial cancers and possibly also
      in hyperplasias and certain dysplasias preceding carcinomas.

PMID- 12208734
TI  - The c-kit tyrosine kinase inhibitor STI571 for colorectal cancer therapy.
AB  - The c-kit tyrosine kinase inhibitor STI571 exhibits a substantial therapeutic
      activity in patients with chronic myeloid leukemia and gastrointestinal stromal
      tumors respectively associated with constitutive activation of the BCR-ABL and c
      kit tyrosine kinases. Human colorectal tumors also express the c-kit proto
      oncogene. The present study focuses on the anticancer activity of STI571 in human
      colorectal tumor cells in vitro and in vivo. The c-kit receptor was identified as
      a M(r) 145,000 immunoreactive band in human colon cancer cells HT29, HCT8/S11,
      and HCT116. Cellular invasion induced by 10 ng/ml stem cell factor (EC(50) = 3
      ng/ml) in HT29 cells was blocked by 1 micro M STI571 (IC(50) = 56 nM) and
      pharmacological inhibitors of several oncogenic signaling pathways, namely,
      phosphatidylinositol 3-kinase (LY294002), Rho GTPases (Clostridium botulinum
      exoenzyme C3 transferase), and Rho-kinase (Y27632). STI571 inhibited HT29 cell
      proliferation (IC(50) = 6 micro M) and induced apoptosis in vitro. These cellular
      effects were associated with a decrease in tumor growth. We also demonstrated
      that stem cell factor is a proangiogenic factor in vivo and in vitro. These
      encouraging results warrant further preclinical investigations and clinical
      trials on the use of the c-kit inhibitor STI571 as a chemotherapeutic agent in
      colon cancer prevention and in treatment of advanced colorectal cancers
      associated with liver metastases.

PMID- 12208735
TI  - Granzyme B-mediated degradation of T-cell receptor zeta chain.
AB  - We recently reported that the T-cell receptor (TCR)-zeta chain is cleaved by
      caspase-3 and -7 in apoptotic T lymphocytes or in a cell-free system. We report
      here that the zeta chain is also a direct substrate for granzyme B (GrB)
      proteolytic activity. Loss in expression of TCR-zeta was observed in Jurkat T
      leukemic cells treated by a combination of GrB and a replication-deficient
      adenovirus. Although the apoptosis initiated in these cells by GrB was
      significantly reduced by the pancaspase inhibitor Z-VAD-FMK, TCR-zeta degradation
      was not prevented. These findings suggest that the GrB-mediated degradation of
      TCR-zeta chain can proceed despite the efficient inhibition of caspase activity.
      An in vitro translated TCR-zeta product was efficiently cleaved by GrB, which
      suggests that the TCR-zeta protein is a direct substrate for GrB. As assessed by
      site-directed mutagenesis, the activity of GrB was directed toward aspartic acid
      residues that were different from those of recombinant caspase-3. Whereas caspase
      3 cleavage products appear to accumulate, the GrB-generated products seem to
      undergo further degradation, which suggests the presence of multiple GrB-specific
      cleavage sites within the TCR-zeta protein. These findings suggest that the TCR
      zeta protein in target T lymphocytes serves as a substrate for the proteolytic
      activities that are featured by the two major mechanisms of cytotoxicity: death
      receptor pathways mediated by caspases and granule exocytosis mediated by direct
      GrB activity or GrB-activated caspases. TCR-zeta protein degradation may be of
      significance in cytotoxic mechanisms directed against T cells infected with
      viruses, such as HIV-1, in which the TCR-zeta protein is used for viral
      pathogenesis.

PMID- 12208736
TI  - The candidate tumor suppressor ING1b can stabilize p53 by disrupting the
      regulation of p53 by MDM2.
AB  - ING1b is a candidate tumor suppressor that can stimulate the transcriptional
      activity of p53 and inhibit cell proliferation. The molecular basis of how ING1b
      activates p53 function remains unclear. Here we show that ING1b could stimulate
      the activity of p53 by increasing the level and stability of the p53 protein. The
      stabilization and activation of p53 by ING1b could be reversed by MDM2 in a dose
      dependent manner. Conversely, ING1b could reverse the inhibition and degradation
      of p53 caused by MDM2 in a dose-dependent manner. Furthermore, ING1b and MDM2
      bound to p53 in a mutually exclusive manner. In agreement with these
      observations, we found that similarly to MDM2, ING1b binds to the NH(2)-terminal
      region of p53. These data suggest a model in which ING1b disrupts the interaction
      between p53 and MDM2, leading to the stabilization of p53 and growth inhibition.

PMID- 12208737
TI  - Peptidomics-based approach reveals the secretion of the 29-residue COOH-terminal
      fragment of the putative tumor suppressor protein DMBT1 from pancreatic
      adenocarcinoma cell lines.
AB  - Deleted in malignant brain tumors 1 is a putative tumor suppressor protein in
      brain, lung, esophageal,gastric, and colorectal cancer. Here we report the mass
      spectrometric identification of a 3335 Da peptide, which was found in serum-free
      conditioned medium from 5 of 15 pancreatic adenocarcinoma cell lines but not from
      35 carcinoma cell lines and 2 nonmalignant pancreatic duct cell lines. The
      peptide was the 29 COOH-terminal amino acids from deleted in malignant brain
      tumors 1. It is suggested that the peptide is generated inside the cells by
      limited proteolysis and extracellularly secreted. Our peptidomics-based approach
      will help screen candidate marker peptides for a particular type of cancer.

PMID- 12208738
TI  - Transcription-coupled nucleotide excision repair as a determinant of cisplatin
      sensitivity of human cells.
AB  - The resistance of tumor cells to chemotherapeutic agents, such as cisplatin,is an
      important problem to be solved in cancer chemotherapy. One of the mechanisms
      associated with cisplatin resistance is nucleotide excision repair (NER). There
      are two pathways in NER, transcription-coupled NER (TC-NER) and global genome NER
      (GG-NER). Here, we report that TC-NER-deficient cells [xeroderma pigmentosum
      group A (XP-A), XP-D, XP-F, XP-G, Cockayne syndrome group A (CS-A), and CS-B] are
      hypersensitive to cisplatin irrespective of their GG-NER status, and that gene
      complementation with XPA and XPD increases resistance to cisplatin. By contrast,
      XP-C cells with selective defect in GG-NER but with normal TC-NER have normal
      resistance to cisplatin. XPC complementation had no effect on cisplatin
      antiproliferative activity. We propose that one of the pathways related to
      cisplatin response is TC-NER, not GG-NER.

PMID- 12208739
TI  - Cyclooxygenase-2 overexpression inhibits death receptor 5 expression and confers
      resistance to tumor necrosis factor-related apoptosis-inducing ligand-induced
      apoptosis in human colon cancer cells.
AB  - The inducible cyclooxygenase-2 (COX-2) gene regulates prostaglandin
      biosynthesis,is up-regulated in colorectal cancers, and can influence apoptotic
      susceptibility. We determined whether forced COX-2 expression modulates apoptosis
      induction by tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), a
      member of tumor necrosis factor ligand family, and examined determinants of the
      apoptotic pathway, including membrane death receptors (DR-4 and DR-5). HCT-15
      colon cancer cells lacking endogenous COX-2 proteins were stably transfected with
      the COX-2 cDNA and incubated with TRAIL. Forced COX-2 expression significantly
      attenuated TRAIL-induced apoptosis and was associated with transcriptional
      repression of DR-5 and up-regulation of Bcl-2. COX-2 transfectants showed reduced
      DR-5 mRNA and protein expression as well as reduced caspase-8, caspase-3, and
      caspase-9 activation relative to parental cells. Sulindac sulfide treatment
      restored DR-5 expression and, when combined with TRAIL, reduced cell viability to
      a greater extent than did either drug alone. In summary, modulation of DR-5 and
      Bcl-2 levels by COX-2 attenuates TRAIL-induced apoptosis and represents a novel
      mechanism of intrinsic drug resistance in human colon cancer cells.

PMID- 12208740
TI  - dUTPase and uracil-DNA glycosylase are central modulators of antifolate toxicity
      in Saccharomyces cerevisiae.
AB  - The thymidylate synthase reaction remains an important target for widely used
      anticancer agents; however, the clinical utility of these drugs is limited by the
      occurrence of cellular resistance. Despite the considerable amount of information
      available regarding mechanisms of drug action, the relative significance of
      downstream events that result in lethality remains unclear. In this study, we
      have developed a model system using the budding yeast Saccharomyces cerevisiae to
      dissect the influence of dUMP misincorporation into DNA as a contributing
      mechanism of cytotoxicity induced by antifolate agents. The activities of dUTPase
      and uracil-DNA glycosylase, key enzymes in uracil-DNA metabolism, were diminished
      or augmented, and the manipulated strains were analyzed for biochemical endpoints
      of toxicity. Cells overexpressing dUTPase were protected from cytotoxicity by
      their ability to prevent dUTP pool expansion and were able to recover from an
      early S-phase checkpoint arrest. In contrast, depletion of dUTPase activity leads
      to the accumulation of dUTP pools and enhanced sensitivity to antifolates. These
      cells were also arrested in early S-phase and were unable to complete DNA
      replication after drug withdrawal, resulting in lethality. Inactivation of uracil
      base excision repair induced partial resistance to early cytotoxicity (within 10
      h); however, lethality ultimately resulted at later time points (12-24 h),
      presumably because of the detrimental effects of stable uracil misincorporation.
      Although these cells were able to complete replication with uracil-substituted
      DNA, they arrested at the G(2)-M phase. This finding may represent a novel
      mechanism by which the G(2)-M checkpoint is signaled by the presence of uracil
      substituted DNA. Together these data provide both genetic and biochemical
      evidence demonstrating that lethality from antifolates in yeast is primarily
      dependent on uracil misincorporation into DNA, and that uracil-independent
      mechanisms associated with dTTP depletion play a minor role. Our findings
      indicate that the relative expression levels of both dUTPase and uracil-DNA
      glycosylase can have great influence over the efficacy of thymidylate synthase
      directed chemotherapy, thereby enhancing the candidacy of these proteins as
      prognostic markers and alternative targets for therapeutic development.

PMID- 12208741
TI  - FK228 (depsipeptide) as a natural prodrug that inhibits class I histone
      deacetylases.
AB  - FK228 is a histone deacetylase (HDAC) inhibitor, the molecular mechanism of
      inhibition of which has been unknown. Here we show that reduction of an
      intramolecular disulfide bond of FK228 greatly enhanced its inhibitory activity
      and that the disulfide bond was rapidly reduced in cells by cellular reducing
      activity involving glutathione. Computer modeling suggests that one of the
      sulfhydryl groups of the reduced form of FK228 (redFK) interacts with the active
      site zinc, preventing the access of the substrate. HDAC1 and HDAC2 were more
      strongly inhibited by redFK than HDAC4 and HDAC6. redFK was less active than
      FK228 in inhibiting in vivo HDAC activity, due to rapid inactivation in medium
      and serum. Thus, FK228 serves as a stable prodrug to inhibit class I enzymes and
      is activated by reduction after uptake into the cells. The glutathione-mediated
      activation also implicates its clinical usefulness for counteracting glutathione
      mediated drug resistance in chemotherapy.

PMID- 12208742
TI  - 2-Methyl-1,4-naphthoquinone, vitamin K(3), decreases gap-junctional intercellular
      communication via activation of the epidermal growth factor
      receptor/extracellular signal-regulated kinase cascade.
AB  - 2-Methyl-1,4-naphthoquinone, vitamin K(3) (menadione), which is frequently used
      as a model quinone in cell culture and in vivo studies, was tested for its
      effects on gap-junctional intercellular communication (GJC). Exposure of WB-F344
      rat liver epithelial cells to menadione (50-100 micro M) led to a 50-75% decrease
      in GJIC. Different from the phorbol ester 12-O-tetradecanoylphorbol 13-acetate,
      menadione did not induce internalization of gap junctions. Rather, the decreased
      GJIC was found to be because of phosphorylation of connexin 43, the major
      connexin in the used cell line, which was mediated by MAPK/ERK kinase (MEK) 1 and
      MEK 2 as well as by activation of their direct substrates, extracellular signal
      regulated kinase (ERK) 1 and ERK 2. Activation of ERK 1/2 was demonstrated to be
      independent of NAD(P)H:quinone oxidoreductase using the inhibitor dicoumarol,
      thus excluding redox cycling as the major mechanism causing these menadione
      effects. A substantial increase in tyrosine phosphorylation was detected in the
      cell membrane immunocytochemically upon exposure to menadione, consistent with
      arylation by menadione bearing the responsibility for the signaling events
      induced and consistent with the fact that protein tyrosine phosphatases are known
      targets of arylation reactions. ERK activation was attenuated using specific
      inhibitors of the epidermal growth factor receptor tyrosine kinase. Similarly,
      these inhibitors as well as inhibitors of MEK 1/2 counteracted the loss in gap
      junctional communication elicited by menadione. This is of interest for
      chemotherapeutic approaches exploiting the bystander-effect, which is based upon
      intact GJIC.

PMID- 12208743
TI  - Role of the phosphatidylinositol 3'-kinase/PTEN/Akt kinase pathway in tumor
      necrosis factor-related apoptosis-inducing ligand-induced apoptosis in non-small
      cell lung cancer cells.
AB  - Tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL)/APO-2L is a
      member of the TNF superfamily and has been shown to have selective antitumor
      activity. We here show that TRAIL does not induce apoptosis in some non-small
      cell lung cancer (NSCLC) cells. These cells are resistant to TRAIL because of the
      phosphatidylinositol 3'-kinase (PI3-K)-dependent activation of Akt/protein kinase
      B. The expression of phospho-Akt varies at the functional level but not at the
      mRNA level in NSCLC cells. Akt induces cell survival in NSCLC cells by blocking
      the Bid cleavage, upstream of cytochrome c release in the mitochondrial-dependent
      apoptotic pathway. The use of PI3-K inhibitors, Wortmannin or LY-294002, down
      regulates the active Akt and reverses cellular resistance to TRAIL. In addition,
      genetically altering Akt expression by transfecting dominant negative Akt,
      sensitizes NSCLC cells to TRAIL. Conversely, transfection of constitutively
      active Akt into cells that express low, constitutively active Akt, increases
      TRAIL resistance. Alternate to this approach, transfection with PTEN, a lipid
      phosphatase, promotes sensitivity to TRAIL, whereas a PTEN mutant (PTEN-G129E) at
      the catalytic site is inactive in dephosphorylating active Akt. Furthermore, the
      loss of PTEN activity or overexpression of PI3-K-dependent Akt/protein kinase B
      activity promotes the survival of NSCLC cells. Modulation of Akt activity by
      combining pharmacological drugs or genetic alterations of the Akt expression
      induces cellular responsiveness to TRAIL. Thus, TRAIL can be used to treat NSCLC
      resistant cells when combined with agents that down-regulate Akt activity.

PMID- 12208744
TI  - Modes of silencing of p16 in development of esophageal squamous cell carcinoma.
AB  - To clarify modes of silencing of p16 and their concerns to the development and
      progression of esophageal squamous cell carcinomas (ESCCs), we examined
      immunoreactivity of p16, loss of heterozygosity (LOH) at six microsatellite loci
      in 9p13-22, and the methylation status of the p16 promoter in 42 cases of the
      ESCC at various stages. The samples taken from step sections in and around the
      tumors were examined to map heterogeneity of those changes. Thereby at least one
      focus of dysplasia was detected in each case. No immunoexpression of p16 was
      detected in the ESCCs of 38 cases (90.5%) and in dysplasias of 34 cases (81%),
      whereas the histologically normal epithelia adjacent to the ESCC showed the p16
      expression even in the presence of p16 methylation. Of the ESCCs/dysplasias
      without p16 expression (38/34), 16/0 showed both p16 methylation and LOH at the
      near-p16 loci (+/+), 14/30 did only methylation (+/-) and 8/4 did only LOH (-/+).
      The presence of LOH with/without homozygous deletion (HD) at the near-p16 loci
      correlated with the advanced tumor stages (P < 0.001). The mapping of +/+ cases
      indicated that the +/+ carcinomas were included in the +/- carcinomas, which
      were, in turn, surrounded by the +/- dysplasias and/or by the +/- normal-looking
      epithelia, whereas the -/+ dysplasias were always accompanied by the -/+
      carcinomas. These results suggest that the mode of p16 silencing either through
      methylation or through LOH and possible mutation is determined in each patient
      before the occurrence of ESCCs and dysplasia. The mapping of HD and p16
      expression suggest that the HD is a later event than the p16 silencing.

PMID- 12208745
TI  - Suppression of 7,12-dimethylbenz(a)anthracene-induced mammary carcinogenesis in
      rats by resveratrol: role of nuclear factor-kappaB, cyclooxygenase 2, and matrix
      metalloprotease 9.
AB  - We have reported recently that resveratrol (trans-3,4',5-trihydroxystilbene), a
      polyphenolic phytoalexin found in grapes, fruits, and root extracts of the weed
      Polygonum cuspidatum, is a potent inhibitor of nuclear factor (NF)-kappaB
      activation. Because NF-kappaB suppression has been linked with chemoprevention,
      this prompted us to investigate the chemopreventive potential of resveratrol by
      testing it against mammary carcinogenesis induced by 7,12
      dimethylbenz(a)anthracene (DMBA) in female Sprague Dawley rats. Dietary
      administration of resveratrol (10 ppm) had no effect on body weight gain and
      tumor volume but produced striking reductions in the incidence (45%; P < 0.05),
      multiplicity (55%; P < 0.001), and extended latency period of tumor development
      relative to DMBA-treated animals. Histopathological analysis of the tumors
      revealed that DMBA induced ductal carcinomas and focal microinvasion in situ (7
      of 7), whereas treatment with resveratrol suppressed DMBA-induced ductal
      carcinoma. Immunohistochemistry and Western blot analysis revealed that
      resveratrol suppressed the DMBA-induced cyclooxygenase-2 and matrix
      metalloprotease-9 expression in the breast tumor. Gel shift analysis showed
      suppression of DMBA-induced NF-kappaB activation by resveratrol. Treatment of
      human breast cancer MCF-7 cells with resveratrol also suppressed the NF-kappaB
      activation and inhibited proliferation at S-G(2)-M phase. Overall, our results
      suggest that resveratrol suppresses DMBA-induced mammary carcinogenesis, which
      correlates with down-regulation of NF-kappaB, cyclooxygenase-2, and matrix
      metalloprotease-9 expression.

PMID- 12208746
TI  - MDR1 gene polymorphisms affect therapy outcome in acute myeloid leukemia
      patients.
AB  - Allelic variants of the MDR-1 gene have been shown recently to influence protein
      expression and P-glycoprotein (P-gp) function in healthy volunteers. Therefore,
      405 acute myeloid leukemia patients were investigated for somatic genotypes of
      the three most frequent single nucleotide polymorphisms (SNPs) in exons 12, 21,
      and 26. In all three loci, homozygous wild-type alleles were classified as
      genotype A, heterozygous as B, and homozygous mutant (alternative) allele as C.
      Patients with the C genotype in exons 12 and 26 showed a lower median age (both P
      < 0.05). Additionally, the C genotype in exons 12 and 26 was associated with
      cytogenetic poor risk aberrations (both P < 0.05). A possible regulatory impact
      of the SNPs on MDR1 mRNA expression was investigated by a Real time-PCR assay.
      MDR1 expression was strongly correlated with a decreased complete remission rate
      (P = 0.01) but failed to predict decreased overall survival (OS). There was a
      significant association of the A genotype in exons 21 (P = 0.05) and 26 (P <
      0.05) with lower MDR1 expression, whereas the B variants showed highest MDR1
      values at all three investigated gene loci. The A genotype in exon 26 was
      associated with lower OS (P < 0,01). In these patients, worse OS is likely
      attributable to an increased risk of relapse (P < 0.001). We were able to detect
      a linkage disequilibrium of the investigated SNPs, indicating combined
      polymorphisms that could affect the regulation of MDR1 expression. The A genotype
      of all SNPs demonstrated both lowest MDR1 values and significantly decreased OS
      (P < 0.05) with a high probability of relapses (P < 0.01). These observations
      indicate that allelic variants of the MDR1 gene may influence therapy outcome by
      additional mechanisms, different from P-gp expression on acute myeloid leukemia
      blasts, possibly involving pharmacokinetic effects of P-gp.

PMID- 12208747
TI  - Translation of microarray data into clinically relevant cancer diagnostic tests
      using gene expression ratios in lung cancer and mesothelioma.
AB  - The pathological distinction between malignant pleural mesothelioma (MPM)and
      adenocarcinoma (ADCA) of the lung can be cumbersome using established methods. We
      propose that a simple technique, based on the expression levels of a small number
      of genes, can be useful in the early and accurate diagnosis of MPM and lung
      cancer. This method is designed to accurately distinguish between genetically
      disparate tissues using gene expression ratios and rationally chosen thresholds.
      Here we have tested the fidelity of ratio-based diagnosis in differentiating
      between MPM and lung cancer in 181 tissue samples (31 MPM and 150 ADCA). A
      training set of 32 samples (16 MPM and 16 ADCA) was used to identify pairs of
      genes with highly significant, inversely correlated expression levels to form a
      total of 15 diagnostic ratios using expression profiling data. Any single ratio
      of the 15 examined was at least 90% accurate in predicting diagnosis for the
      remaining 149 samples (e.g., test set). We then examined (in the test set) the
      accuracy of multiple ratios combined to form a simple diagnostic tool. Using two
      and three expression ratios, we found that the differential diagnoses of MPM and
      lung ADCA were 95% and 99% accurate, respectively. We propose that using gene
      expression ratios is an accurate and inexpensive technique with direct clinical
      applicability for distinguishing between MPM and lung cancer. Furthermore, we
      provide evidence suggesting that this technique can be equally accurate in other
      clinical scenarios.

PMID- 12208749
TI  - Transcriptional regulation of vascular endothelial growth factor by estradiol and
      tamoxifen in breast cancer cells: a complex interplay between estrogen receptors
      alpha and beta.
AB  - Vascular endothelial growth factor (VEGF) is a potent angiogenic and prognostic
      factor for many tumors, including those of endocrine-responsive tissues such as
      the breast and uterus. Recent studies indicate that 17beta-estradiol (E(2))
      modulates VEGF expression in breast and uterine cells, involving transcriptional
      activation through estrogen receptor (ER) alpha. However, molecular mechanisms of
      VEGF regulation mediated by the two ER subtypes and the potential role of ERbeta
      in the control of breast cancer angiogenesis have not yet been investigated. In
      transient transfection assays using the VEGF(-2275/+54) promoter-luciferase
      construct, E(2) (1 nM) increased transcription activity in MCF-7 cells (either
      untransfected or cotransfected with ERalpha) and it increased transcription
      activity in MDA-MB-231 cells cotransfected with ERalpha or ERbeta (1.8- and 2
      fold induction, respectively). The positive effect was abolished when MCF-7 cells
      were treated with pure antiestrogen ICI 182,780 or the agonist/antagonist
      tamoxifen (1 micro M). To identify response elements involved in this
      transcriptional regulation, MCF-7 or MDA-MB-231 cells were transfected with
      several deletion constructs of the VEGF promoter. Deletion of 1.2-2.3 kb upstream
      to the transcription start in the VEGF promoter abrogated E(2)-dependent
      transcription in these cells. This region contains an imperfect estrogen
      responsive element (ERE), ERE1520, and one activator protein 1 site. Transfection
      of MCF-7 cells (ERalpha) with the ERE1520-luciferase construct conferred
      transcriptional activity with 1 nM E(2) (1.9-fold induction). Also, the imperfect
      ERE formed a complex with ERalpha or ERbeta proteins in gel shift assay using MCF
      7 or MDA-MB-231 nuclear extracts. In contrast to ERalpha, ERbeta could
      transactivate VEGF reporter construct in MDA-MB-231 cells, in the presence of
      E(2) or tamoxifen, suggesting different transactivational mechanisms between
      ERalpha and ERbeta in the presence of tamoxifen. Interestingly, E(2) inhibited
      VEGF transcription in MCF-7 cells transfected with ERbeta or MDA-MB-231 cells
      cotransfected with ERalpha and ERbeta, suggesting that heterodimerization of
      ERalpha/ERbeta has the ability to inhibit E(2)-induced VEGF expression in breast
      cancer cells. These results demonstrate that VEGF is a target gene for ERalpha
      and ERbeta in breast cancer cells; it remains to be determined whether ERalpha
      and ERbeta expression in breast biopsies correlates with VEGF expression and
      vascular density.

PMID- 12208748
TI  - Phase I study of replication-competent adenovirus-mediated double suicide gene
      therapy for the treatment of locally recurrent prostate cancer.
AB  - Adenovirus-mediated suicide gene therapy may hold promise in the treatment of
      human cancer. We have developed a novel approach that utilizes a lytic,
      replication-competent adenovirus (Ad5-CD/TKrep) to deliver a cytosine
      deaminase/herpes simplex virus-1 thymidine kinase fusion gene to tumors. The
      cytosine deaminase and herpes simplex virus-1 thymidine kinase suicide genes
      render malignant cells sensitive to specific pharmacological agents and,
      importantly, sensitize them to radiation. The Phase I study described here
      represents the first gene therapy trial in which a replication-competent virus
      was used to deliver a therapeutic gene to humans. The indication is local
      recurrence of prostate cancer after definitive radiation therapy. An escalating
      dose (10(10), 10(11), and 10(12) viral particles) of the Ad5-CD/TKrep virus was
      injected intraprostatically under transrectal ultrasound guidance into 16
      patients in four cohorts. Two days later, patients were given 5-fluorocytosine
      and ganciclovir prodrug therapy for 1 (cohorts 1-3) or 2 (cohort 4) weeks. There
      were no dose-limiting toxicities, and the maximum tolerated dose of the Ad5
      CD/TKrep vector was not defined. Ninety-four percent of the adverse events
      observed were mild or moderate (grade 1/2) in nature. Seven of 16 (44%) patients
      demonstrated a >or=25% decrease in serum prostate-specific antigen, and 3 of 16
      (19%) patients demonstrated a >or=50% decrease in serum prostate-specific
      antigen. Transgene expression and tumor destruction at the injection site were
      confirmed by sextant needle biopsy of the prostate at 2 weeks. Two patients were
      negative for adenocarcinoma at 1 year follow-up. Although Ad5-CD/TKrep viral DNA
      could be detected in blood as far out as day 76, no infectious adenovirus was
      detected in patient serum or urine. Together, the results demonstrate that
      intraprostatic administration of the replication-competent Ad5-CD/TKrep virus
      followed by 2 weeks of 5-fluorocytosine and ganciclovir prodrug therapy can be
      safely applied to humans and is showing signs of biological activity.

PMID- 12208750
TI  - Overexpression of DNA-binding protein B gene product in breast cancer as detected
      by in vitro-generated combinatorial human immunoglobulin libraries.
AB  - Molecules differentially expressed or overexpressed by malignant cells can serve
      in detecting and tracking of tumor. Additionally, they potentially can be applied
      in histologic-specific antitumor therapy. Few breast cancer-associated candidate
      molecules have been identified. Here we describe the use of combinatorial
      immunoglobulin [antigen-binding fragment of immunoglobulin molecule (Fab)
      fragment] phage libraries generated from patients with breast carcinoma to
      identify cancer-associated gene expression. The libraries were enriched for tumor
      binding Fab by 3 logs and yielded a group of antibodies against DNA-binding
      protein B (DbpB), a 35-kDa thrombin-inducible nuclear factor and member of the Y
      box family of proteins, which are known to act both negatively in selective gene
      suppression and positively as promoters of gene transcription. Sequencing of the
      anti-DbpB showed a degree of heterogeneity and bp substitutions suggesting that
      the Fabs selected from the combinatorial library represented a varied anti-DbpB
      immune response and did not simply arise from in vitro amplification by PCR of a
      single or limited numbers of immunoglobulin genes. Sequencing of the DbpB
      molecule expressed in malignant breast cancer showed no evidence of tumor
      specific mutations. Evaluation of levels of DbpB gene product expression however
      showed the molecule to be constitutively expressed in normal nonmalignant breast
      tissues but to have consistently differentially higher expression in breast
      cancer. Immunohistological staining revealed DbpB to be present both
      intracellularly and on the cell surface, which suggests it may be a means whereby
      malignant cells repair and replicate DNA in a selectively advantageous manner as
      compared with nonmalignant cells. DbpB expression in breast cancer may advance
      the basic understanding of the role of Y-box binding proteins as regulatory
      agents, and in defining malignant cell phenotypes. In addition, DbpB and the
      antibodies generated against it may have direct application in tumor detection
      and in molecule-targeted immunotherapy.

PMID- 12208751
TI  - A novel polymorphism in human cytosine DNA-methyltransferase-3B promoter is
      associated with an increased risk of lung cancer.
AB  - DNA repair is central to genomic integrity. Reduced expression of several
      nucleotide excision repair genes has been demonstrated to be associated with
      increased risk of lung cancer. Because methylation of gene promoters is one of
      the major regulatory mechanisms of gene expression and most nucleotide excision
      repair gene promoters have not been fully characterized, we hypothesized that
      genetic variants of the genes that are responsible for regulating genomic
      methylation are associated with increased risk of lung cancer. Recently, we
      identified a C-->T transition at a novel promoter region of cytosine DNA
      methyltransferase-3B (DNMT3B) and found that this polymorphic transition
      significantly increases the promoter activity. In this hospital-based case
      control study of 319 patients with incident lung cancer and 340 healthy controls
      frequency matched on age (+/-5 years), sex, ethnicity, and smoking status, we
      genotyped subjects for this DNMT3B promoter polymorphism to determine the
      association between this genetic variant and risk of lung cancer. Compared with
      CC homozygotes, CT heterozygotes had a >2-fold increased risk of lung cancer
      [adjusted odds ratio (OR), 2.13; 95% confidence interval (CI), 1.47-3.08] and TT
      homozygotes an OR of 1.42 (95% CI, 0.91-2.21). The combined variant genotype (CT
      + TT) was associated with a nearly 2-fold increased risk (adjusted OR, 1.88; 95%
      CI, 1.32-2.66). These results suggest that this novel variant of DNMT3B is
      associated with increased risk of lung cancer and may contribute to identifying
      individuals genetically susceptible to tobacco-induced cancers. Additional
      studies on the underlying molecular mechanism of this polymorphism are warranted.

PMID- 12208752
TI  - Proteasome inhibitor PS-341 inhibits human myeloma cell growth in vivo and
      prolongs survival in a murine model.
AB  - The proteasome is a ubiquitous and essential intracellular enzyme that degrades
      many proteins regulating cell cycle, apoptosis, transcription, cell
      adhesion,angiogenesis, and antigen presentation. We have shown recently that the
      proteasome inhibitor PS-341 inhibits growth, induces apoptosis, and overcomes
      drug resistance in human myeloma cells in vitro. In this study, we examined the
      efficacy, toxicity, and in vivo mechanism of action of PS-341 using a human
      plasmacytoma xenograft mouse model. One hundred immunodeficient (beige-nude-xid)
      mice were used in two independent experiments. The mice were injected s.c. with 3
      x 10(7) RPMI-8226 myeloma cells. When tumors became measurable (9.2 days; range,
      6-13 days after tumor injection), mice were assigned to treatment groups
      receiving PS-341 0.05 mg/kg (n = 13), 0.1 mg/kg (n = 15), 0.5 mg/kg (n = 14), or
      1.0 mg/kg (n = 14) twice weekly via tail vein, or to control groups (n = 13)
      receiving the vehicle only. Significant inhibition of tumor growth, even with
      some complete tumor regression, was observed in PS-341-treated mice. The median
      overall survival was also significantly prolonged compared with controls (30 and
      34 days for high dose-treated mice versus 14 days for controls; P < 0.0001). PS
      341 was well tolerated up to 0.5 mg/kg, but some mice treated at 1.0 mg/kg became
      moribund and lost weight. Analysis of tumors harvested from treated animals
      showed that PS-341 induced apoptosis and decreased angiogenesis in vivo. These
      studies therefore demonstrate that PS-341 has significant in vivo antimyeloma
      activity at doses that are well tolerated in a murine model, confirming our in
      vitro data and further supporting the early clinical promise of PS-341 to
      overcome drug resistance and improve patient outcome.

PMID- 12208753
TI  - Efficacy and toxicity of a virus-directed enzyme prodrug therapy purging method:
      preclinical assessment and application to bone marrow samples from neuroblastoma
      patients.
AB  - Autologous stem cell transplantation is used to rescue cancer patients from
      myelosuppression caused by high-dose chemotherapy. However, autologous grafts
      often contain tumor cells that can contribute directly to relapse. Current
      purging methods are useful when fewer than 1% tumor cells contaminate the bone
      marrow, and patients with tumor burdens of >1% are considered ineligible for
      chemotherapy that necessitates stem cell rescue. Using neuroblastoma (NB) as a
      model system, we developed a method that is effective even with tumor burdens of
      10-25%. Mixtures of NB-1691 NB cells and CD34(+) hematopoietic cells purged by
      this method showed no evidence of viable tumor cells as assessed by clonogenic
      assays or reverse transcription-PCR for the NB cell markers tyrosine hydroxylase
      and N-MYC. The efficacy and lack of toxicity of the method were verified using in
      vivo mouse models. Severe combined immunodeficient mice that received purged cell
      preparations containing 10% NB-1691 cells survived without evidence of disease
      for the observation period (>1 year), whereas mice that received unpurged cells
      developed disseminated disease requiring euthanasia 73-96 days after injection of
      cells. No evidence of toxicity to the mice was detected by numerous laboratory
      values for bone marrow, liver, and kidney function, and no difference was seen in
      the ability of purged cell mixtures versus unmanipulated CD34(+) cells to
      reconstitute the marrow of non-obese diabetic severe combined immunodeficient
      mice. In a pilot study, marrow was obtained from eight patients who had >/=1%
      metastatic tumor burden. All eight samples were purged to the level of detection
      by reverse transcription-PCR (samples from seven patients) or clonogenic
      potential (sample from one patient), whichever assay was used. The described
      adenovirus/rabbit carboxylesterase/CPT-11 (irinotecan, 7-ethyl-10[4-(1
      piperidino)-1-piperidino]carbonyloxycamptothecin) virus-directed enzyme prodrug
      method may be useful for patients whose tumor burdens exceed 1% at the time of
      stem cell harvest. Assessment of purging efficacy with additional samples from NB
      patients is ongoing.

PMID- 12208754
TI  - Nuclear localization of proteasomes participates in stress-inducible resistance
      of solid tumor cells to topoisomerase II-directed drugs.
AB  - Physiological cell conditions of solid tumors, such as glucose starvation and
      hypoxia,induce cellular resistance to topoisomerase II-directed drugs. Here, we
      show that the induction of drug resistance is mediated by nuclear accumulation of
      proteasomes, large multicatalytic protease complexes. We found that the nuclear
      proteasome accumulation during glucose starvation was attenuated by stable
      expression of a mutant type of proteasome subunit, XAPC7, that lacked the nuclear
      localization signal (NLS). It is important that the expression of NLS-defective
      XAPC7 also diminished the induction of resistance to etoposide and doxorubicin,
      typical topoisomerase II-directed drugs. Under normal conditions, however, the
      NLS-defective XAPC7 had little effect on either nuclear proteasome distribution
      or etoposide sensitivity. Our findings demonstrate that stress-induced nuclear
      proteasome accumulation occurs through up-regulation of the NLS-dependent
      transport. Inhibition of the nuclear proteasome accumulation can be a novel
      approach to circumventing resistance to topoisomerase II-directed drugs.

PMID- 12208755
TI  - Efficient and nontoxic adenoviral purging method for autologous transplantation
      in breast cancer patients.
AB  - Tumor cell contamination of clinical grafts is a major concern in autologous
      hematopoietic stem cell transplantation because these contaminating cells can
      contribute to relapse. In the present work, we use a suicide gene therapy
      approach that successfully accomplishes the two main goals of any purging
      strategy: highly efficient elimination of contaminating tumor cells and
      preservation of the engraftment capability of the hematopoietic progenitor cells.
      Human CD34(+) cells spiked with breast cancer cells were infected with an
      adenoviral vector encoding the cytosine deaminase transgene (Ad-CMV-CD). In
      vitro, transduction with Ad-CMV-CD followed by exposure to 400 micro M 5
      fluorocytosine resulted in complete elimination of clonogenic contaminating tumor
      cells without affecting the clonogenic potential of the human hematopoietic
      CD34(+) cells. Transplantation of nonobese diabetic/LtSz-scid/severe combined
      immunodeficient (NOD/SCID) mice with nonpurged contaminated grafts and purged
      contaminated grafts, allowed us to test the safety and efficacy of our procedure
      in two independent purging experiments. Hematopoietic engraftment kinetics as
      well as the quantity and quality of human engraftment were not affected by the
      purging therapy. Results showed a significant difference in survival between the
      nonpurged group (28%) and the purged group (100%; P = 0.012). Moreover, highly
      sensitive histological and molecular analyses confirmed the absence of tumor
      cells in the recipients of purged marrow. In contrast, metastatic tumors were
      detected in animals that received nonpurged grafts. We anticipate that this
      strategy will result in a safe and efficacious hematopoietic graft product for
      autologous transplantation for patients with multiple forms of epithelial
      cancers.

PMID- 12208756
TI  - The vascular endothelial growth factor receptor tyrosine kinase inhibitor
      PTK787/ZK222584 inhibits growth and migration of multiple myeloma cells in the
      bone marrow microenvironment.
AB  - Our prior studies show that multiple myeloma (MM) cell lines and patient cells
      express high-affinity vascular endothelial growth factor (VEGF) receptor (VEGFR)
      Flt-1 but not Flk-1/KDR. Moreover, these studies have shown that VEGF induces
      proliferation and migration of MM cells, and we have begun to delineate the
      signaling cascades mediating those sequelae. In this study, we examined the
      activity of PTK787/ZK 222584 (PTK787), a molecule designed to bind specifically
      to the tyrosine kinase domain of VEGFR and inhibit angiogenesis. We show that
      PTK787 acts both directly on MM cells and in the bone marrow microenvironment.
      Specifically, PTK787 (1-5 micro M) inhibits proliferation of MM cells by 50%, as
      assayed by [(3)H]thymidine uptake. This effect of PTK787 is dose dependent in
      both MM cell lines and patient cells that are both sensitive and resistant to
      conventional therapy. PTK787 enhances the inhibitory effect of dexamethasone on
      growth of MM cells and can overcome the protective effect of interleukin 6 (IL-6)
      against dexamethasone-induced apoptosis. PTK787 (1 micro M) also blocks VEGF
      induced migration of MM cells across an extracellular matrix. Importantly, PTK787
      also inhibits the increased MM cell proliferation and increased IL-6 and VEGF
      secretion in cultures of MM cells adherent to bone marrow stem cells. These
      findings therefore demonstrate that PTK787 both acts directly on MM cells and
      inhibits paracrine IL-6-mediated MM cell growth in the bone marrow milieu. The
      demonstrated anti-MM activity of PTK787, coupled with its antiangiogenic effects,
      provides the framework for clinical trials of this agent to overcome drug
      resistance and improve outcome in MM.

PMID- 12208757
TI  - Enhanced sensitivity of multiple myeloma cells containing PTEN mutations to CCI
      779.
AB  - Recent work identifies the AKT kinase as a potential mediator of tumor expansion
      in multiple myeloma. The finding of PTEN mutations in several myeloma cell lines
      suggests that loss of PTEN function may be one mechanism by which AKT activity is
      increased in this disease. Because PTEN-deficient myeloma cells may have up
      regulated activity of the mammalian target of rapamycin (mTOR), downstream of
      AKT, they may be particularly sensitive to mTOR inhibition. To test this
      hypothesis, we challenged myeloma cell lines with CCI-779, a newly developed
      analogue of rapamycin and an efficient inhibitor of mTOR. Three of four PTEN
      deficient cell lines with constitutively active AKT were remarkably sensitive to
      cytoreduction and G(1) arrest induced by CCI-779 with ID(50) concentrations of <1
      nM. In contrast, myeloma cells expressing wild-type PTEN were >1000-fold more
      resistant. Acute expression of a constitutively active AKT gene in CCI-779
      resistant myeloma cells containing wild-type PTEN and quiescent AKT did not
      convert them to the CCI-779-sensitive phenotype. Conversely, expression of wild
      type PTEN in CCI-779-sensitive, PTEN-deficient myeloma cells did not induce
      resistance. Differential sensitivity did not appear to be due to differences in
      the ability of CCI-779 to inhibit mTOR and induce dephosphorylation of
      p70S6kinase or 4E-BP1. However, CCI-779 inhibited expression of c-myc in CCI
      sensitive PTEN-null myeloma cells but had no effect on expression in CCI
      resistant cells. In contrast, cyclin D1 expression was not altered in either
      sensitive or resistant cells. These results indicate that PTEN-deficient myeloma
      cells are remarkably sensitive to mTOR inhibition. Although the results of
      transfection studies suggest that the level of PTEN and AKT function per se does
      not regulate sensitivity, PTEN/AKT status may be a good predictive marker of
      sensitivity.

PMID- 12208758
TI  - Overexpression of wild-type breast cancer resistance protein mediates
      methotrexate resistance.
AB  - Previously, we have reported that a multidrug-resistant, mitoxantrone (MX)
      selected cell line, MCF7/MX, is highly cross-resistant to the antifolate
      methotrexate (MTX), because of enhanced ATP-dependent drug efflux (E. L. Volk et
      al., Cancer Res., 60: 3514-3521, 2000). These cells overexpress the breast cancer
      resistance protein (BCRP), and resistance to MTX as well as to MX was reversible
      by the BCRP inhibitor, GF120918. These data indicated that BCRP causes the
      multidrug-resistance phenotype. To further examine the role of this transporter
      in MTX resistance, and in particular the role of amino acid 482, we analyzed a
      number of BCRP-overexpressing cell lines. MTX resistance correlated with BCRP
      expression in all of the cell lines expressing the wild-type transporter, which
      contains an Arg at position 482. In contrast, little or no cross-resistance was
      found in the MCF7/AdVp1000 and S1-M1-3.2 and S1-M1-80 cell lines, which contain
      acquired mutations at this position, R482T and R482G, respectively.
      Concomitantly, the greatest reduction in MTX accumulation was observed in the
      MCF7/MX cells (BCRP(Arg)) as compared with cells expressing the Thr and Gly BCRP
      variants. Furthermore, the reduction in drug accumulation was sensitive to BCRP
      inhibition by GF120918. In conclusion, we have demonstrated a novel role for BCRP
      as a mediator of MTX resistance and have provided further evidence for the
      importance of amino acid 482 in substrate specificity.

PMID- 12208759
TI  - Enhanced induction of telomerase-specific CD4(+) T cells using dendritic cells
      transfected with RNA encoding a chimeric gene product.
AB  - Dendritic cells (DCs) transfected with mRNA encoding human telomerase reverse
      transcriptase (hTERT) have been shown to represent potent inducers of CTLs and
      antitumor immunity. However, it has become widely accepted that not only CTLs but
      also CD4(+) T helper cells are critical to the generation, as well as to the
      maintenance, of potent antitumor responses in vivo. In this study, we sought to
      determine whether human DCs transfected with mRNA encoding a chimeric
      hTERT/lysosome-associated membrane protein (LAMP-1) protein, carrying the
      endosomal/lysosomal sorting signal of the LAMP-1, are capable of stimulating
      concomitant hTERT-specific CD8(+) and CD4(+) T-cell responses in vitro. We show
      that processing of hTERT/LAMP-1 transcripts leads to enhanced stimulation of
      hTERT-specific CD4(+) T cells and does not negatively affect intracellular
      generation and subsequent presentation of MHC class I epitopes, hence, generating
      a CTL response. These findings provide a preclinical rationale of using DCs
      transfected with the chimeric hTERT/LAMP-1 RNA in vaccine trials to facilitate
      generation of antigen-specific CD4(+) T-cell responses that may be required to
      stimulate and maintain an optimal CD8(+) CTL response in vivo.

PMID- 12208760
TI  - Carcinoembryonic antigen as a target for specific antitumor immunotherapy of head
      and neck cancer.
AB  - Human carcinoembryonic antigen (CEA) is an oncofetal glycoprotein overexpression
      of which by gastrointestinal carcinomas is well known. Expression of CEA in head
      and neck cancer (HNC) is not widely recognized. It is important to note that most
      of these studies used polyclonal antibodies that may have cross-reactivity with
      CEA-related antigens. Currently, CEA is being evaluated in preclinical and
      clinical studies as a target for specific immunotherapy against gastrointestinal
      adenocarcinomas that express the antigen. This study was conducted to evaluate
      CEA as a potential target for specific immunotherapy against HNC.
      Immunohistochemical analysis of tumor tissue from 69 cases of squamous cell
      carcinoma (SCC) of the head and neck using a CEA-specific monoclonal antibody
      (COL-1) showed the majority to be positive for CEA. Tumor cell lines derived from
      human HNC were screened for CEA transcripts using nested reverse transcription
      PCR. Constitutive expression of CEA mRNA was detected in 7 of 10 HNC lines. CEA
      protein was detectable in lysates from all 7 of the lines by quantitative
      fluoroimmunometry. SDS-PAGE/Western blot analysis of cell lysates from these
      lines showed a COL-1 immunoreactive product with a molecular weight equivalent to
      that of CEA. Cell surface expression of CEA was low for the SCC lines; however,
      there was moderate to strong cytoplasmic staining intensity for all of the CEA(+)
      HNC lines by immunocytochemistry. Additional supportive evidence for CEA as a
      target was demonstrated by the presence of cytolytic activity of an HLA-A2
      restricted/CEA-epitope-specific human CTL against a CEA-overexpressing HNC
      derived SCC line. These results suggest that CEA may be considered as a possible
      target for specific vaccine-mediated immunotherapy against HNCs.

PMID- 12208761
TI  - Identification of an interferon-gamma-inducible carcinoembryonic antigen (CEA)
      CD8(+) T-cell epitope, which mediates tumor killing in CEA transgenic mice.
AB  - This study describes a CD8(+) T-cell line specific for a MHC class I-restricted
      carcinoembryonic antigen (CEA) epitope, residues 526-533, isolated from CEA
      transgenic (CEA.Tg) mice immunized with a recombinant vaccinia-CEA vaccine.
      Incubation of splenocytes from the immune CEA.Tg mice with the CEA(526-533)
      peptide resulted in the outgrowth of low-avidity CD8(+) T cells, which produced
      IFN-gamma and mediated perforin-dependent tumor cell lysis. However, the CEA
      peptide-specific T cells killed CEA-expressing murine colorectal tumor cells only
      after pretreatment of the targets with murine IFN-gamma (muIFN-gamma), and lysis
      was H-2D(b)-restricted and involved the Fas-FasL-mediated cytotoxic pathway. When
      the CEA peptide-specific T cells were used as in vivo effectors in adoptive T
      cell transfer studies, muIFN-gamma treatment of the CEA.Tg mice was again
      required for T-cell-dependent growth suppression of CEA-expressing metastatic
      tumors. The results indicate that (a) vaccination of mice carrying the human CEA
      gene with recombinant vaccinia-CEA generates a CEA epitope-specific, CD8
      dependent CTL response, (b) CEA, a normal, tissue-specific antigen, can also
      serve as a target for antitumor immunity after the adoptive transfer of CEA
      peptide-specific T cells, and (c) muIFN-gamma might be an effective cancer
      vaccine adjuvant by virtue of its ability to augment the susceptibility of tumor
      targets to cell-mediated lysis.

PMID- 12208762
TI  - Activated CD8+ T lymphocytes induce differentiation of monocytes to dendritic
      cells and restore the stimulatory capacity of interleukin 10-treated antigen
      presenting cells.
AB  - We analyzed the role of CD8+ T cells on dendritic cells (DCs). Incubation of
      monocytes with activated but not resting CD8+ T cells induced their
      differentiation into DCs with a CD1a+ and CD14- phenotype. Activated CD8+
      lymphocytes induced down-regulation of CD14 expression in interleukin (IL)-10
      treated macrophages and resulted in the expression of DC-related CD1a and up
      regulation of mRNA transcripts for RelB, IL-12p40, MCP-2, MIP-1alpha, and ELC.
      These DCs were potent stimulatory cells in mixed lymphocyte reaction and induced
      primary CTL responses. This interaction was independent of a direct cell-to-cell
      contact. Monoclonal antibodies against IFN-gamma completely abolished the CD1a
      induction on IL-10-treated antigen-presenting cells. These results demonstrate
      that CD8+ cells can provide stimulatory signals to antigen-presenting cells to
      induce their differentiation in DC and to increase their immunostimulatory
      capacity.

PMID- 12208763
TI  - Macrophages as effector cells in interleukin 12-induced T cell-dependent tumor
      rejection.
AB  - Interleukin (IL)-12 activates a T-cell-dependent antitumor immune response that
      is able to eradicate established large tumors in a number of immunogenic tumor
      models. The effector mechanisms in these dramatic antitumor responses have not
      yet been identified. In this report, we show that the effector mechanism of IL-12
      induced rejection of established MCA207 tumors is unique in that it is not
      dependent on perforin, Fas/Fas ligand, and nitric oxide. Study of
      cyclophosphamide plus IL-12 (Cy + IL-12)-induced rejection of ascites Sa1 tumor
      demonstrates that macrophages are the predominant immune cell infiltration in the
      ascites. These macrophages possess nonspecific tumoricidal activity in vivo as
      immune distinct MCA207 tumor cells inoculated i.p., but not s.c., in mice bearing
      regressing Sa1 ascites tumors after Cy + IL-12 therapy are rejected. Furthermore,
      Cy + IL-12-treated Sa1 ascites cells or macrophages, but not spleen macrophages
      from the same mouse or inflammatory macrophages induced by thioglycollate, are
      able to suppress the development of immune-irrelevant s.c. tumors in a Winn
      assay. These macrophages kill various tumor cells in a contact-dependent manner
      in vitro, and the cytotoxicity is preserved after fixation with paraformaldehyde.
      These results demonstrate that activated macrophages function as effector cells
      in an IL-12-induced, T-cell-dependent eradication of established tumors through a
      novel contact-dependent, paraformaldehyde fixation-resistant, apoptosis-inducing
      mechanism.

PMID- 12208764
TI  - Constitutive p38HOG mitogen-activated protein kinase activation induces permanent
      cell cycle arrest and senescence.
AB  - Cellular senescence, initially observed during subculturing of normal diploid
      fibroblasts, can also be induced by chronic exposure to cellular stress, such as
      UV light, oxidative stress, or DNA damaging agents. Here we demonstrate that
      stable expression of an activated form of MKK6 (MKK6EE), a direct activator of
      the stress-induced p38(HOG) mitogen-activated protein kinase pathway, is
      sufficient for inducing features of senescence including a flattened, vacuolated,
      and irregular morphology, staining for acidic beta-galactosidase, and
      accumulation of age-associated pigments. Consistent with the senescent phenotype,
      p38(HOG) activation induces a G(1) cell cycle arrest, which is permanent and
      irreversible after 4 days. MKK6EE also induces biochemical features of senescence
      in a p38-dependent manner, including enhanced expression of p21(CIP), a cyclin
      dependent kinase inhibitor. Microarray analysis of MKK6EE cells showed a pattern
      of gene expression noted previously in Werner Syndrome and senescent fibroblasts.
      These results define p38(HOG) as an intracellular pathway that activates a
      senescence checkpoint in tumor cells and may play a role in Ras- or stress
      induced senescence.

PMID- 12208765
TI  - The colon anion transporter, down-regulated in adenoma, induces growth
      suppression that is abrogated by E1A.
AB  - The down-regulated in adenoma (DRA) gene is significantly down-regulated in
      adenomas and adenocarcinomas of the colon as well as in colon cancer cell lines.
      It is also mutated in the disease congenital chloride diarrhea, which is
      characterized by loss of chloride transport and diarrhea. We now show a second
      function for DRA relevant to colon tumorigenesis, i.e., growth suppression.
      Transfection of full-length DRA into various cell lines (DLD-1, HT-29, HCT-15,
      SW837, SW480, MCF-7, NIH3T3, CaSki, and HeLa) that lack endogenous DRA expression
      results in a reduced number of drug-resistant colonies compared with vector
      control, suggesting growth suppression by DRA. In addition, expression of DRA
      under the control of an inducible promoter reduced the growth rate of DLD-1 cells
      compared with cells not expressing DRA. The COOH-terminal cytoplasmic domain of
      DRA is required for growth suppression, but an in-frame deletion (DeltaVal317)
      that causes congenital chloride diarrhea and results in a loss of anion transport
      had no effect on growth suppression, indicating that anion transport and growth
      suppression are independent functions of DRA. One cell line, adenovirus
      transformed HEK293, exhibited significant resistance to DRA-induced growth
      suppression, whereas the human papillomavirus-transformed cell lines, CaSki and
      HeLa, did not. E1A is an adenoviral protein required to transform HEK293 cells.
      DLD-1 cells that stably express 12S E1A are resistant to growth suppression by
      DRA, similar to HEK293 cells.

PMID- 12208766
TI  - The redox protein thioredoxin-1 (Trx-1) increases hypoxia-inducible factor 1alpha
      protein expression: Trx-1 overexpression results in increased vascular
      endothelial growth factor production and enhanced tumor angiogenesis.
AB  - Hypoxia-inducible factor 1 (HIF-1), a heterodimer of HIF-1alpha and HIF-1beta
      subunits, is a transcriptional activator central to the cellular response to low
      oxygen that includes metabolic adaptation, angiogenesis, metastasis, and
      inhibited apoptosis. Thioredoxin-1 (Trx-1) is a small redox protein overexpressed
      in a number of human primary tumors. We have examined the effects of Trx-1 on HIF
      activity and the activation of downstream genes. Stable transfection of human
      breast carcinoma MCF-7 cells with human Trx-1 caused a significant increase in
      HIF-1alpha protein levels under both normoxic (20% oxygen) and hypoxic (1%
      oxygen) conditions. Trx-1 increased hypoxia-induced HIF-1 transactivation
      activity measured using a luciferase reporter under the control of the hypoxia
      response element. Changes in HIF-1alpha mRNA levels did not account for the
      changes observed at the protein level, and HIF-1beta protein levels did not
      change. Trx-1 transfection also caused a significant increase in the protein
      products of hypoxia-responsive genes, including vascular endothelial growth
      factor (VEGF) and nitric oxide synthase 2 in a number of different cell lines
      (MCF-7 human breast and HT29 human colon carcinomas and WEHI7.2 mouse lymphoma
      cells) under both normoxic and hypoxic conditions. The pattern of expression of
      the different isoforms of VEGF was not changed by Trx-1. Transfection of a redox
      inactive Trx-1 (C32S/C35S) markedly decreased levels of HIF-1alpha protein, HIF-1
      transactivating activity, and VEGF protein in MCF-7 cells compared with empty
      vector controls. In vivo studies using WEHI7.2 cells transfected with Trx-1
      showed significantly increased tumor VEGF and angiogenesis. The results suggest
      that Trx-1 increases HIF-1alpha protein levels in cancer cells and increases VEGF
      production and tumor angiogenesis.

PMID- 12208767
TI  - Fibroblast growth factor 8 isoform B overexpression in prostate epithelium: a new
      mouse model for prostatic intraepithelial neoplasia.
AB  - Fibroblast growth factor 8 isoform b (FGF8b), a mitogenic and transforming
      polypeptide, was demonstrated to be naturally up-regulated in prostatic
      premalignant and malignant lesions in men. We generated four independent lines of
      transgenic mice with targeted overexpression of FGF8b in the prostatic epithelium
      using an improved rat probasin promoter, ARR(2)PB. Transgene expression in the
      prostate tissue was readily demonstrated by reverse transcription-PCR and
      localized to the prostatic epithelium by in situ hybridization. The
      histopathology of the prostate tissues was followed in different age groups of
      the various lines but most extensively in one line (line 3), starting from 1
      month of age up to 24 months. Prostatic hyperplasia appeared in the lateral and
      ventral prostates in some animals as early as 2-3 months and in other lobes
      between 6 and 16 months. Beginning at 5-7 months, dysplasia, akin to what may be
      considered low-grade prostatic intraepithelial neoplasia (LGPIN) in humans, was
      detected. During the first 14 months, 100% of animals exhibited multifocal
      epithelial hyperplasia; 35% also had areas of LGPIN. This profile changed in
      subsequent months (15-24 months) to a higher incidence of LGPIN (66%) along with
      high-grade PIN (HGPIN) lesions (51%). Similar to HGPIN, stromal proliferation and
      appearance of papillary hyperplasia with atypia displayed a delayed pattern. The
      affected stroma consisted primarily of the smooth muscle cell component. The
      incidence of chronic inflammation, mostly involving T cells, was higher in the
      prostate of the transgenic mice relative to controls; however, the presence of a
      direct correlation between inflammation and hyperplasia or preneoplastic lesions
      was not identified. These transgenic mice represent a "natural" animal model for
      investigating the mechanism of development and progression of prostatic diseases,
      such as prostatic hyperplasia and preneoplastic lesions.

PMID- 12208768
TI  - Fully human antibodies to MCAM/MUC18 inhibit tumor growth and metastasis of human
      melanoma.
AB  - MCAM/MUC18 expression correlates with tumor thickness and metastatic potential of
      human melanoma cells in nude mice. Moreover, ectopic expression of MUC18 in
      primary cutaneous melanoma cells leads to increased tumor growth and metastasis
      in vivo. Here we tested the effect of a fully human anti-MUC18 antibody, ABX-MA1,
      on angiogenesis, tumor growth, and metastasis. ABX-MA1 had no effect on melanoma
      cell proliferation rate in vitro. However, when cells of the metastatic melanoma
      lines A375SM and WM2664 (which express high levels of MUC18) were injected s.c.
      into nude mice and treated with ABX-MA1 (100 micro g, weekly, i.p. for 5 weeks),
      tumor growth was significantly inhibited compared with control IgG-treated mice.
      ABX-MA1 treatment also suppressed experimental lung metastasis of these melanoma
      cells. ABX-MA1 disrupted spheroid formation by melanoma cells expressing MUC18
      (homotypic interaction) and the ability of these cells to attach to human
      vascular endothelial cells [HUVECs (MUC18 positive)] in vitro. ABX-MA1 treatment
      of melanoma cells in vitro significantly inhibited the promoter and collagenase
      activity of matrix metalloproteinase 2, resulting in decreased invasion through
      Matrigel-coated filters. Decreased expression of matrix metalloproteinase 2 was
      also observed in the implanted tumors in vivo. Moreover, because HUVECs also
      express MUC18, ABX-MA1 directly disrupted the tube-like formation by HUVECs in an
      in vitro vessel formation assay. Collectively, these results point to usefulness
      of ABX-MA1 as a modality to treat melanoma either alone or in combination with
      conventional chemotherapy or other antitumor agents.